PMID- 9907992
TI  - Diffusion-reaction kinetics for A+B(static)-->C(inert) for one-dimensional
      systems with initially separated reactants.

PMID- 9907993
TI  - Self-organization and a dynamical transition in traffic-flow models.

PMID- 9907994
TI  - Surface growth with temporally correlated noise.

PMID- 9907995
TI  - Modulation mechanism for first-order transformations with nonconserved order
      parameters.

PMID- 9907996
TI  - Theoretical sandpile with stochastic slide.

PMID- 9907997
TI  - Exact results for a three-body reaction-diffusion system.

PMID- 9907998
TI  - Novel cross-roll state in a cylindrical convection cell with thermally conducting
      sidewalls.

PMID- 9907999
TI  - Probability distribution for three-dimensional vectors of velocity increments in
      turbulent flow.

PMID- 9908000
TI  - Atomistic simulation of heat and mass transfer near the convection threshold.

PMID- 9908002
TI  - Spreading of smectic-A droplets: Structure and dynamics of terraces.

PMID- 9908001
TI  - Phase-ordering dynamics of nematic liquid crystals.

PMID- 9908003
TI  - Effect of surface crystal-E order on the interior smectic-A-hexatic-B transition.

PMID- 9908005
TI  - Structure factor for randomly oriented self-affine membranes.

PMID- 9908004
TI  - Continuous thermodynamic path between three smectic-A phases of the same
      symmetry.

PMID- 9908006
TI  - Disorientation-induced disordering at a nematic-liquid-crystal-solid interface.

PMID- 9908007
TI  - Upper limits for frequency up-conversion in the nonlinear photon accelerator.

PMID- 9908008
TI  - Criticality in the one-dimensional Kohonen neural map.

PMID- 9908009
TI  - Generalization in a two-layer neural network.

PMID- 9908010
TI  - Irreversible evolution of isolated quantum systems and a discreteness of time.

PMID- 9908011
TI  - Two-center shell potential: Spectral fluctuations and an effective underlying
      classical dynamics.

PMID- 9908013
TI  - Dispersion forces, self-reaction, and electromagnetic fluctuations.

PMID- 9908012
TI  - Perturbed factorization of the symmetric-anharmonic-oscillator eigenequation.

PMID- 9908014
TI  - Macroscopic and mesoscopic changes of entropies in detectors and collapse in
      quantum-measurement processes.

PMID- 9908015
TI  - Quantum deformations of the discrete nonlinear Schrodinger equation.

PMID- 9908016
TI  - Noise-induced reduction of wave packets and faster-than-light influences.

PMID- 9908017
TI  - Path-integral solutions for shape-invariant potentials using point canonical
      transformations.

PMID- 9908018
TI  - Applications of the unitary-group approach to variational calculations in many
      electron atoms.

PMID- 9908020
TI  - Nuclear polarization in d micro and t micro atoms and in the dt micro molecule.

PMID- 9908019
TI  - Calculations of the Auger deexcitation rate of dt micro within the muonic
      quasimolecule (dt micro)dee.

PMID- 9908021
TI  - Correlation-function hyperspherical-harmonic calculation of the microdt molecular
      ion.

PMID- 9908022
TI  - Matrix-element calculations for hydrogenlike atoms.

PMID- 9908024
TI  - Comparison of kinetic-energy density functionals.

PMID- 9908023
TI  - Energy of 1s2ns (n=3, 4, and 5) states for the lithium isoelectronic sequence.

PMID- 9908025
TI  - Self-localized energy transfer in a dissipative environment.

PMID- 9908026
TI  - Electron-pair analysis for doubly excited ridge states.

PMID- 9908027
TI  - Branching ratio of the H-(n=2) shape resonance.

PMID- 9908028
TI  - Cross sections for electron scattering by atomic potassium.

PMID- 9908029
TI  - Elastic scattering of hydrogen atoms at low temperatures.

PMID- 9908030
TI  - Photon polarization in radiative recombination of bare ions with low-energy free
      electrons.

PMID- 9908031
TI  - Collisional ionization and excitation of H2: Dependence on the orientation of the
      internuclear axis.

PMID- 9908032
TI  - Classical-path theory for broadening of atomic lines by diatomic perturbers.

PMID- 9908033
TI  - Electronic excitation of carbon monoxide by low-energy electron impact.

PMID- 9908034
TI  - Convergent close-coupling calculations of electron-hydrogen scattering.

PMID- 9908035
TI  - Intercomparison of atomic models for computing stopping parameters from the Bethe
      theory: Atomic hydrogen.

PMID- 9908036
TI  - Neutral decay of double-holed doubly excited resonances of N2.

PMID- 9908038
TI  - Metal-cluster fission and the liquid-drop model.

PMID- 9908037
TI  - Observation of molecular-beam magnetic resonance of Li3 clusters.

PMID- 9908039
TI  - Light-shift optical coherent averaging in rubidium vapors.

PMID- 9908040
TI  - Microwave ionization of Na atoms in weak-to-strong static electric fields.

PMID- 9908041
TI  - Calculation of a linear Stark effect on the 254-nm line of Hg.

PMID- 9908042
TI  - Probe transmission in one-dimensional optical molasses: Theory for linearly cross
      polarized cooling beams.

PMID- 9908043
TI  - Magnetic and mechanical Faraday effects.

PMID- 9908044
TI  - Configuration-space methods for Coulomb scattering in a laser field.

PMID- 9908046
TI  - Two-dimensional forces and atomic motion in a sub-Doppler limit.

PMID- 9908045
TI  - Observation of Stark-induced-dipole-quadrupole interference in atomic barium.

PMID- 9908047
TI  - Non-Markovian behavior in stimulated photon echoes: Waiting-time dependence.

PMID- 9908049
TI  - Temporal and spatial reflectivity of focused beams in stimulated Brillouin
      scattering for phase conjugation.

PMID- 9908048
TI  - Approach to the theory of radiation-matter interaction for arbitrary field
      strength.

PMID- 9908050
TI  - Rydberg states and spin-orbit coupling of the thallium atom.

PMID- 9908051
TI  - Phase conjugation using the surface nonlinearity of a dense potassium vapor.

PMID- 9908052
TI  - Spontaneous emission in a standing-wave cavity: Classical center-of-mass motion.

PMID- 9908053
TI  - Theoretical study of resonant ultrashort-pulse propagation in semiconductors.

PMID- 9908054
TI  - Two-mode nonclassical state via superpositions of two-mode coherent states.

PMID- 9908055
TI  - Coupled-channel cavity QED model and exact solutions.

PMID- 9908056
TI  - Nonlinear sublevel-coherence effects in the phase-conjugate emission of Doppler
      broadened dilute media.

PMID- 9908057
TI  - Collective collapses and revivals in spontaneous emission of a partially inverted
      system of two-level atoms: Analytical solution.

PMID- 9908058
TI  - Calculation of multiphoton-ionization Green's functions using the Wentzel-Kramers
      Brillouin approximation. II.

PMID- 9908059
TI  - Quantum theory of optical multistability in a two-photon three-level Lambda 
      configuration medium.

PMID- 9908061
TI  - cw instability and steady-state pulses in a ring laser with intracavity
      parametric amplification.

PMID- 9908060
TI  - Four-wave-mixing processes in translational optomechanical media.

PMID- 9908062
TI  - Conservation laws in superfluorescence.

PMID- 9908063
TI  - Probability for double photoionization of He and Ne.

PMID- 9908064
TI  - Vanishing of transition amplitudes in the Floquet theory of periodic
      interactions.

PMID- 9908065
TI  - Neutron-interferometer absorption experiments in the quantum limit.

PMID- 9908066
TI  - Exact perturbation theory for quantum-mechanical systems within boxes.

PMID- 9908067
TI  - Geometry of projective Hilbert space.

PMID- 9908068
TI  - General theorem on the Schrodinger equation.

PMID- 9908069
TI  - Analytic evaluation of the inner-vertex correction to the decay rate of
      orthopositronium in the Fried-Yennie gauge.

PMID- 9908070
TI  - Faddeev calculation of the dt micro- mesic molecule.

PMID- 9908071
TI  - Cloud of virtual photons surrounding a two-level atom driven by an external
      field.

PMID- 9908072
TI  - Loss of state purity and regularity in the Jaynes-Cummings model.

PMID- 9908073
TI  - Chaos and order in second-harmonic generation: Cumulant approach.

PMID- 9908075
TI  - Stability of dark solitons: Linear analysis.

PMID- 9908074
TI  - Modulating ionization through phase control.

PMID- 9908076
TI  - High-order harmonic generation in atomic hydrogen at 248 nm: Dipole-moment versus
      acceleration spectrum.

PMID- 9908077
TI  - Comment on "Relativistic excitation energies and oscillator strengths for the 6s2
      1S0-->6s6p 1P1,3P1 transitions in Hg-like ions"

PMID- 9908078
TI  - Erratum: Resonance fluorescence of a two-level atom in a strong bichromatic field

PMID- 9908080
TI  - Multielectron transitions resulting from interactions between target and
      projectile electrons in ionizing collisions.

PMID- 9908079
TI  - Erratum: Classical impulse approximation for the electron loss from H(1s) or H-
      projectiles passing through various gas targets

PMID- 9908081
TI  - Partial-wave formulation in the calculation of atomic and molecular ionization
      cross sections.

PMID- 9908083
TI  - Lasers without inversion: Two-photon stimulated emission in a three-level atom.

PMID- 9908082
TI  - Planar ion microtraps.

PMID- 9908084
TI  - Molecular H2 in intense laser fields probed by electron-electron, electron-ion,
      and ion-ion covariance techniques.

PMID- 9908085
TI  - Lossless transformation of coherent light into amplitude-squeezed light.

PMID- 9908086
TI  - Spin squeezing and reduced quantum noise in spectroscopy.

PMID- 9908087
TI  - Quantum trajectory simulations of two-state behavior in an optical cavity
      containing one atom.

PMID- 9908088
TI  - Analysis and synthesis of synchronous periodic and chaotic systems.

PMID- 9908089
TI  - Scaling analysis of time-dependent simulations of the three-dimensional contact
      process.

PMID- 9908090
TI  - Unitarity and irreversibility in chaotic systems.

PMID- 9908091
TI  - Stochastic transition of free motion in billiards with borders given by
      equipotential lines of the diamagnetic Kepler problem.

PMID- 9908092
TI  - Interpolation between the Grover-Silbey and the generalized stochastic Liouville
      equation theories.

PMID- 9908093
TI  - Tracking unstable orbits in experiments.

PMID- 9908094
TI  - Dynamical model of an earthquake fault with localization.

PMID- 9908095
TI  - Phase transitions in the approximated and asymptotic generalized entropy spectrum
      of a nonhyperbolic system.

PMID- 9908096
TI  - Double-critical-point phenomena in three-component liquid mixtures: Light
      scattering investigations.

PMID- 9908097
TI  - Shape of inflated vesicles.

PMID- 9908098
TI  - Grain-boundary instabilities and buckling in partially polymerized membranes.

PMID- 9908099
TI  - Extended Lyapunov exponents.

PMID- 9908100
TI  - Instabilities and nonstatistical behavior in globally coupled systems.

PMID- 9908101
TI  - Diffusion equation for energy in ergodic adiabatic ensembles.

PMID- 9908102
TI  - Relaxation spectrum of quantum harmonic motion in the presence of nonlinear
      dissipative-diffusive couplings.

PMID- 9908103
TI  - Evolution of disorder in magnetic stripe domains. I. Transverse instabilities and
      disclination unbinding in lamellar patterns.

PMID- 9908104
TI  - Evolution of disorder in magnetic stripe domains. II. Hairpins and labyrinth
      patterns versus branches and comb patterns formed by growing minority component.

PMID- 9908105
TI  - Frequency- and wave-vector-dependent dielectric function of waterlike fluids.

PMID- 9908107
TI  - Multistate cellular automaton for reaction-diffusion processes.

PMID- 9908106
TI  - Theory of the density expansion of the dynamic structure factor: The pair
      contribution.

PMID- 9908108
TI  - Bifurcation phenomena in nonaxisymmetric Taylor-Couette flow.

PMID- 9908110
TI  - Symmetry breaking in nonequilibrium systems: Interaction of defects.

PMID- 9908109
TI  - Isothermal shear-induced heat flow.

PMID- 9908111
TI  - Turbulent transport of a passive-scalar field by using a renormalization-group
      method.

PMID- 9908112
TI  - Control of vortex shedding in a two-dimensional flow past a plate.

PMID- 9908113
TI  - Dynamic scaling and quasiordered states in the two-dimensional Swift-Hohenberg
      equation.

PMID- 9908114
TI  - Uniaxial-to-biaxial cholesteric and nematic phase transitions on a lyotropic
      alcohol-free mixture.

PMID- 9908115
TI  - Kinetics of nucleation and growth in a near-critical binary liquid mixture at
      rest and under a shear flow.

PMID- 9908116
TI  - Volumetric and x-ray investigations of the crystalline and columnar phases of
      copper (II) soaps under pressure.

PMID- 9908117
TI  - Integral-equation theory of polydisperse Yukawa systems.

PMID- 9908118
TI  - Behavior of a first-order smectic-A-smectic-C transition in free-standing liquid
      crystal films.

PMID- 9908119
TI  - Wetting and domain-growth kinetics in confined geometries.

PMID- 9908120
TI  - Simulation and theory of two-phase flow in porous media.

PMID- 9908121
TI  - Smectic-A ordering at a liquid-vapor interface.

PMID- 9908122
TI  - Changing mechanical properties of lipid vesicle bilayers investigated by linear
      viscoelastic measurements.

PMID- 9908123
TI  - Linear viscoelasticity of colloidal suspensions.

PMID- 9908124
TI  - Dielectric relaxation of a reentrant nematic-liquid-crystal mixture by time
      domain reflectometry.

PMID- 9908125
TI  - Terraced spreading of simple liquids on solid surfaces.

PMID- 9908126
TI  - Aggregation in polystyrene-sphere suspensions in near-critical binary liquid
      mixtures.

PMID- 9908127
TI  - Nonlinear hydrodynamics and the liquid-glass transition: A numerical study.

PMID- 9908128
TI  - Defect dynamics and coarsening dynamics in smectic-C films.

PMID- 9908129
TI  - Coarsening following a morphological instability in the one-sided model.

PMID- 9908130
TI  - Ferroelectric liquid-crystal and solid phases formed by strongly interacting
      dipolar soft spheres.

PMID- 9908131
TI  - Theory of branched growth.

PMID- 9908132
TI  - Heating of solid targets by subpicosecond laser pulses.

PMID- 9908133
TI  - Dynamical N-body simulations of Coulomb scattering in plasma sheaths.

PMID- 9908135
TI  - Analytic model of the cathode region of a short glow discharge in light gases.

PMID- 9908134
TI  - Nonlinear shaping of a two-dimensional ultrashort ionizing pulse.

PMID- 9908136
TI  - Characterization of an x-ray-flux source for the production of high-energy
      density plasmas.

PMID- 9908137
TI  - Stability of isotropic self-similar dynamics for scalar-wave collapse.

PMID- 9908139
TI  - Dielectric permeability of quasi-two-dimensional one-component plasmas.

PMID- 9908138
TI  - Intensity ratio of Lyman- alpha fine-structure components of Ti XXII in the JT-60
      tokamak plasma.

PMID- 9908140
TI  - Boltzmann equation and Monte Carlo analysis of electron-electron interactions on
      electron distributions in nonthermal cold plasmas.

PMID- 9908142
TI  - Characteristics of a dusty nonthermal plasma from a particle-in-cell Monte Carlo
      simulation.

PMID- 9908141
TI  - Excess electron mobility in high-density argon gas.

PMID- 9908143
TI  - Numerical and experimental diagnostics of rf discharges in pure and dusty argon.

PMID- 9908144
TI  - One-dimensional analysis of the spiking behavior in a free-electron laser.

PMID- 9908146
TI  - Using wavelets to solve the Burgers equation: A comparative study.

PMID- 9908145
TI  - Experimental studies of nonlinear beam dynamics.

PMID- 9908147
TI  - Deformation and adhesion of elastic bodies in contact.

PMID- 9908149
TI  - Unified theory of collapse, folding, and glass transitions in associative-memory
      Hamiltonian models of proteins.

PMID- 9908148
TI  - Gap solitons in diatomic lattices.

PMID- 9908151
TI  - Modified self-consistent phonon calculation of the dependence of DNA melting
      temperature on guanine-cytosine content.

PMID- 9908150
TI  - Spectral analysis of erythrocyte flickering in the 0.3-4- microm-1 regime by
      microinterferometry combined with fast image processing.

PMID- 9908152
TI  - Derivative of the hard-sphere radial distribution function at contact.

PMID- 9908153
TI  - Dynamical properties of a Cartesian product of two fractals.

PMID- 9908154
TI  - Phase transitions in the problem of the decay of a metastable state.

PMID- 9908155
TI  - Time-dependent transition rates for a multilevel quantum system interacting with
      a bath lacking a characteristic relaxation time.

PMID- 9908156
TI  - Comparison between the homogeneous-shear and the sliding-boundary methods to
      produce shear flow.

PMID- 9908158
TI  - Peculiarities of wave scattering by fat fractals.

PMID- 9908157
TI  - Frequency conversion of radiation pulses in the presence of plasma waves.

PMID- 9908159
TI  - Comment on "Numerical method for colored-noise generation and its application to
      a bistable system"

PMID- 9908160
TI  - Reply to the "Comment on 'Numerical method for colored-noise generation and its
      application to a bistable system' "

PMID- 9908161
TI  - Erratum: Chaos and order of laser-cooled ions in a Paul trap

PMID- 9908162
TI  - Renormalization-group study of field-theoretic A+A-->0-slash.

PMID- 9908163
TI  - Dynamics of the globally coupled complex Ginzburg-Landau equation.

PMID- 9908164
TI  - Dynamic scaling and crossover analysis for the Kuramoto-Sivashinsky equation.

PMID- 9908165
TI  - Noise-spike-induced escape in a bistable system driven by colored noise: Noise
      with long correlation times.

PMID- 9908166
TI  - Synchronization of regular and chaotic systems.

PMID- 9908167
TI  - Strongly intermittent chaos and scaling in an earthquake model.

PMID- 9908168
TI  - Hydrogen-bond cooperativity and free-volume effects on normal and supercooled
      water self-diffusion.

PMID- 9908169
TI  - Tempered diffusion: A transport process with propagating fronts and inertial
      delay.

PMID- 9908170
TI  - Transient bimodality in turbulence-1-turbulence-2 transition in
      electrohydrodynamic convection in nematic liquid crystals.

PMID- 9908171
TI  - Wedge fjord model for dendritic growth.

PMID- 9908173
TI  - Double devil's staircase in circle maps.

PMID- 9908172
TI  - Effect of a partial Siberian snake on an "rf-induced" depolarizing resonance.

PMID- 9908175
TI  - Stochastic resonance in transient dynamics.

PMID- 9908174
TI  - Horseshoes in a relativistic Hamiltonian system in 1+1 dimensions.

PMID- 9908176
TI  - Chaos and coherence in an optical system subject to photon nondemolition
      measurement.

PMID- 9908177
TI  - Asymptotic distribution of the pseudo-orbits and the generalized Euler constant
      gamma Delta for a family of strongly chaotic systems.

PMID- 9908178
TI  - Universal power law observed in an exponentially growing particle system.

PMID- 9908179
TI  - Scaling law for the idler near a bifurcation.

PMID- 9908180
TI  - Complete statistical thermodynamics of the cluster solid-liquid transition.

PMID- 9908181
TI  - Bounds for the Renyi entropies and dynamical phase transitions.

PMID- 9908182
TI  - Length spectrum and semiclassical density of states for an almost-integrable
      billiard system.

PMID- 9908183
TI  - Transition rates in a stochastic medium.

PMID- 9908184
TI  - Gravity in one dimension: Stability of periodic orbits.

PMID- 9908185
TI  - Bethe solution for the dynamical-scaling exponent of the noisy Burgers equation.

PMID- 9908186
TI  - Reaction front for A+B-->C diffusion-reaction systems with initially separated
      reactants.

PMID- 9908187
TI  - Gas dynamics of the pulsed emission of a perfect gas with applications to laser
      sputtering and to nozzle expansion.

PMID- 9908188
TI  - Ring kinetic theory for tagged-particle problems in lattice gases.

PMID- 9908189
TI  - Propagating confined states in phase dynamics.

PMID- 9908190
TI  - Mutual and self-diffusion in fluids undergoing strong shear.

PMID- 9908192
TI  - Numerical study of the influence of forcing terms and fluctuations near onset on
      the roll pattern in Rayleigh-Benard convection in a simple fluid.

PMID- 9908191
TI  - Scaling in hard turbulent Rayleigh-Benard flow.

PMID- 9908193
TI  - Structural and dynamical transformations between neighboring dense microemulsion
      phases.

PMID- 9908195
TI  - Disordered-surface-layer transition in nematic liquid crystals.

PMID- 9908194
TI  - Theory of acoustic properties near the cholesteric-twisted-grain-boundary-A phase
      transition in liquid crystals.

PMID- 9908196
TI  - Determination of the dielectric biaxiality in a chiral smectic-C phase.

PMID- 9908198
TI  - Dynamical wavelength selection by tilt domains in thin-film lamellar eutectic
      growth.

PMID- 9908197
TI  - Nuclear-magnetic-resonance study of silica gelation kinetics.

PMID- 9908200
TI  - Question of dynamical universality in models for phase separation.

PMID- 9908199
TI  - Calorimetric study of a closed reentrant nematic region.

PMID- 9908201
TI  - Variation with amphiphilic strength of the properties of ternary mixtures.

PMID- 9908202
TI  - Invasion percolation into a percolating cluster.

PMID- 9908203
TI  - Structure of the He-Xe mixture near the 30-MPa demixing curve at T=294 K.

PMID- 9908204
TI  - Phase shift of dielectric rolls in electroconvection.

PMID- 9908205
TI  - Instability and phase separation of a binary mixture: The role of short-range
      repulsion and core-size ratio.

PMID- 9908206
TI  - Simulation of the impedance of two-dimensional porous electrodes.

PMID- 9908207
TI  - Formula of the generalized dimensions for the screened-growth model.

PMID- 9908208
TI  - Surface-tension-anisotropy measurements of succinonitrile and pivalic acid:
      Comparison with microscopic solvability theory.

PMID- 9908209
TI  - Bridge functions and improvement on the hypernetted-chain approximation for
      classical one-component plasmas.

PMID- 9908211
TI  - Self-consistent Monte Carlo simulation of the cathode fall including treatment of
      negative-glow electrons.

PMID- 9908210
TI  - Screening potentials in strongly coupled plasmas: Reanalysis of recent highly
      accurate simulations.

PMID- 9908213
TI  - Detailed simulations of plasma-induced spectral blueshifting.

PMID- 9908212
TI  - General-relativistic hydrodynamics of a collisionless plasma in a strong magnetic
      field.

PMID- 9908214
TI  - Experiments and simulations of tunnel-ionized plasmas.

PMID- 9908216
TI  - Coupling impedance of many holes in a liner within a beam pipe.

PMID- 9908215
TI  - Coupling impedance of a single hole in a thick-wall beam pipe.

PMID- 9908218
TI  - Tuning the Kenkre-Campbell self-trapping transition.

PMID- 9908217
TI  - Control-parameter scaling in a Hopfield-Tank list-matching network.

PMID- 9908219
TI  - Quantum and semiclassical Husimi distributions for a one-dimensional resonant
      system.

PMID- 9908220
TI  - Evidence for structural effects in self-diffusion.

PMID- 9908221
TI  - Local interactions in renormalization methods for Navier-Stokes turbulence.

PMID- 9908222
TI  - Photon statistics in a free-electron laser with an axial-guide magnetic field.

PMID- 9908223
TI  - Physical relation between quantum mechanics and solitons on a thin elastic rod.

PMID- 9908225
TI  - Reply to "Comment on 'Liquid-liquid phase separation and critical exponents in
      ionic fluid mixtures' "

PMID- 9908224
TI  - Comment on "Liquid-liquid phase separation and critical exponents in ionic fluid
      mixtures"

PMID- 9908227
TI  - Multicritical two-dimensional vertex models.

PMID- 9908226
TI  - Exact solution of the Kramers problem in periodic potentials.

PMID- 9908228
TI  - First-passage time, maximum displacement, and Kac's solution of the telegrapher
      equation.

PMID- 9908229
TI  - Observation of chaotic bursting and attractor switching in a fluid.

PMID- 9908230
TI  - Surface-mediated electroclinic effect in a chiral nematic liquid crystal.

PMID- 9908231
TI  - Ground state of an electrorheological fluid.

PMID- 9908232
TI  - Geometrical anchoring at an inclined surface of a liquid crystal.

PMID- 9908233
TI  - Phase diagram exhibiting a smectic-A-smectic-C-smectic-F meeting point.

PMID- 9908234
TI  - Instability in a continuum kinetic-growth model with surface relaxation.

PMID- 9908235
TI  - Dynamical double hysteresis in weakly ionized magnetoplasmas.

PMID- 9908237
TI  - QED model for concentrating condensed matter.

PMID- 9908236
TI  - Extinction theorem, dispersion forces, and latent heat.

PMID- 9908238
TI  - Computational approach to the quantum Zeno effect: Position measurements.

PMID- 9908239
TI  - Quantum mechanics in terms of non-negative smoothed Wigner functions.

PMID- 9908241
TI  - Tunneling and group velocity in the square potential barrier.

PMID- 9908240
TI  - Hamiltonian formulation of quantum mechanics with semiclassical implications. II.
      Variational treatment.

PMID- 9908242
TI  - Multichannel quantum defects calculated using a smooth reaction matrix.

PMID- 9908243
TI  - Oscillator strengths and radiative branching ratios in atomic Sr.

PMID- 9908244
TI  - Relativistic ab initio calculation of the xenon 5s ionization spectra for the (
      gamma,e) and (e,2e) reactions.

PMID- 9908245
TI  - Electron capture and loss to continuum from 200-keV/u H0 and He0 projectiles
      colliding with He and Ar targets.

PMID- 9908246
TI  - Positron scattering from rare gases (He, Ne, Ar, Kr, Xe, and Rn): Total cross
      sections at intermediate and high energies.

PMID- 9908247
TI  - J-mixing cross sections in the intermediate nD states of a Rydberg Cs atom.

PMID- 9908248
TI  - Absolute doubly differential cross sections for electron emission in collisions
      of 3.5-MeV/u Fe17+ and Fe22+ ions with He and Ar gas targets.

PMID- 9908249
TI  - Collisional energy transfer between excited-state strontium and noble-gas atoms.

PMID- 9908250
TI  - Faddeev calculation of e--Ps scattering lengths.

PMID- 9908251
TI  - Rydberg spectroscopy of single-electron capture in low-energy collisions of Ar9+
      and Ar8+ with cesium.

PMID- 9908252
TI  - Collision spectroscopy of Ar8+ + He at low velocities (v<1 a.u.).

PMID- 9908253
TI  - Electron-impact dissociative excitation of H3+

PMID- 9908254
TI  - Experimental determination of photoelectron angular distributions for 6S1/2-->
      epsilon P photoionization of Cs near the Cooper minimum.

PMID- 9908255
TI  - Multiplet-dependent shake-up structures in high-resolution Auger spectra at 3d
      14s24p6np,n=5,6 resonances of Kr.

PMID- 9908256
TI  - High-frequency interaction-induced rototranslational scattering from gaseous
      nitrogen.

PMID- 9908257
TI  - Relativistic multichannel calculation of the Ne KLL and Ar L2M2,3M2,3 Auger
      transition rates.

PMID- 9908258
TI  - Light-ion-induced K-shell ionization in the adiabatic region.

PMID- 9908259
TI  - K-shell ionization of O4+ and C2+ ions in fast collisions with H2 and He gas
      targets.

PMID- 9908260
TI  - Vibrational excitation of molecules in electron scattering.

PMID- 9908261
TI  - Scaling of the cross sections for vibrational transitions.

PMID- 9908263
TI  - Interferometer within a molecule.

PMID- 9908262
TI  - Spectra of symmetric-top molecules and the quantum-deformed-symmetric-top model.

PMID- 9908264
TI  - Quantum fluctuations of the optical forces on atoms in a squeezed vacuum.

PMID- 9908265
TI  - Recoil-induced resonances in nonlinear spectroscopy.

PMID- 9908266
TI  - Entropy production and kinetic effects of light.

PMID- 9908268
TI  - Closed-orbit theory of oscillations in atomic photoabsorption cross sections in a
      strong electric field. II. Derivation of formulas.

PMID- 9908267
TI  - Closed-orbit theory of oscillations in atomic photoabsorption cross sections in a
      strong electric field. I. Comparison between theory and experiments on hydrogen
      and sodium above threshold.

PMID- 9908269
TI  - Resonantly enhanced refractive index without absorption via atomic coherence.

PMID- 9908270
TI  - Resonant above-threshold ionization of atomic hydrogen.

PMID- 9908271
TI  - Quantum-nondemolition-measurement scheme using a Kerr medium.

PMID- 9908272
TI  - Non-Markovian master equation for linear and nonlinear systems.

PMID- 9908273
TI  - Phase properties and atomic coherent trapping in the system of a three-level atom
      interacting with a bimodal field.

PMID- 9908274
TI  - Quantum-statistical analysis of superfluorescence and amplified spontaneous
      emission in dense media.

PMID- 9908276
TI  - Theory of a homogeneously broadened laser with arbitrary mirror outcoupling:
      Intrinsic linewidth and phase diffusion.

PMID- 9908275
TI  - Theoretical study of the suppression of thermal background in the Raman-enhanced
      nondegenerate four-wave-mixing spectrum by a time-delayed method.

PMID- 9908277
TI  - Theory of a two-mode phase-sensitive amplifier.

PMID- 9908278
TI  - Eigenstates of two-photon annihilation operators.

PMID- 9908279
TI  - Kink solitons and optical shocks in dispersive nonlinear media.

PMID- 9908280
TI  - Rydberg-atom phase-sensitive detection and the quantum Zeno effect.

PMID- 9908281
TI  - Higher-order squeezing in three- and four-wave mixing processes with loss.

PMID- 9908282
TI  - Coupled-mode analysis of the self-induced-transparency soliton switch.

PMID- 9908283
TI  - Observation of high gain in Ne-like Ag lasers.

PMID- 9908284
TI  - Experimental investigation of double-pass amplification of an x-ray laser in
      neonlike germanium.

PMID- 9908285
TI  - Nonlinear susceptibility of composite optical materials in the Maxwell Garnett
      model.

PMID- 9908287
TI  - Stabilization of atoms in ultrastrong laser fields: A classical approach.

PMID- 9908286
TI  - Suitability of the master-equation approach for micromasers with non-Poissonian
      pumping.

PMID- 9908288
TI  - Analytic solution for inversion and intensity of the Jaynes-Cummings model with
      cavity damping.

PMID- 9908289
TI  - Application of the eigenvalue moment method to the quartic anharmonic double-well
      oscillator.

PMID- 9908290
TI  - Quantum-state space metric and correlations.

PMID- 9908291
TI  - Quantum versus classical dynamics in a periodically driven anharmonic oscillator.

PMID- 9908292
TI  - Vibrational autoionization of hot bands in methyl iodide.

PMID- 9908293
TI  - Fano factor in xenon.

PMID- 9908294
TI  - Double-excitation effects on the angular distribution of photoelectrons from
      strontium.

PMID- 9908295
TI  - Hyperspherical approach to double-electron excitation of He by fast-ion impact.
      III. Excitation to the (2l,2l') manifold by multiply-charged-ion impact.

PMID- 9908296
TI  - Vibrational structure in core-level photoelectron spectra: Periodic trends.

PMID- 9908297
TI  - Alternate time scale in multimode lasers.

PMID- 9908298
TI  - Creating multiphase coherent states in a damped anharmonic oscillator.

PMID- 9908300
TI  - Erratum: Perturbative-variational calculations in two-well anharmonic oscillators

PMID- 9908299
TI  - Generation of orthonormalized eigenstates of the operator ak (for k >= 3) from
      coherent states and their higher-order squeezing.

PMID- 9908301
TI  - Erratum: Partially linearized Thomas-Fermi-Weizsacker theory for screening and
      stopping of charged particles in jellium

PMID- 9908302
TI  - Direct numerical solution of the Schrodinger equation for quantum scattering
      problems.

PMID- 9908303
TI  - Destructive and constructive interferences of the second Born amplitudes for
      positronium formation.

PMID- 9908304
TI  - Landau quantization of electrons on a sphere.

PMID- 9908305
TI  - Conditions for Bose-Einstein condensation in magnetically trapped atomic cesium.

PMID- 9908306
TI  - Laser-induced autoionization of transient molecules.

PMID- 9908308
TI  - Multiphoton ionization of a three-electron atom: Studies with 25-keV Al beams.

PMID- 9908307
TI  - Quantization of the nonlinear Schrodinger equation.

PMID- 9908310
TI  - Curvature disorder in tethered membranes: A new flat phase at T=0.

PMID- 9908309
TI  - Observation of quadrature squeezing in a cavity-atom system.

PMID- 9908311
TI  - Influence of noise on periodic attractors in the Lorenz model: Zero-frequency
      spectral peaks and chaos.

PMID- 9908312
TI  - Statistical properties of time-dependent wave functions for classically chaotic
      bound and scattering systems.

PMID- 9908313
TI  - Reconstruction of vector fields: The case of the Lorenz system.

PMID- 9908314
TI  - Directed alternating lattices and the site-to-bond ratio for animals and trees.

PMID- 9908315
TI  - Critical temperature of (d+1)-dimensional Ising films.

PMID- 9908316
TI  - Light-scattering fluctuations and thermal noise in photorefractive media.

PMID- 9908317
TI  - Effective potentials and chaos in quantum systems.

PMID- 9908318
TI  - Scaling, phase transitions, and nonuniversality in a self-organized critical
      cellular-automaton model.

PMID- 9908320
TI  - Scaled Langevin equation to describe the 1/f alpha spectrum.

PMID- 9908319
TI  - Improved analytical formulas for x-ray and neutron reflection from surface films.

PMID- 9908321
TI  - Coupled maps on fractal lattices.

PMID- 9908322
TI  - Apollonian tiling, the Lorentz group, and regular trees.

PMID- 9908323
TI  - Dynamics in pattern-forming systems.

PMID- 9908324
TI  - Anomalously rough sandpiles in one dimension: Exact decimation results.

PMID- 9908325
TI  - Quantum fractal noise: Time-autocorrelation functions.

PMID- 9908326
TI  - Free energy and specific heat of critical films and surfaces.

PMID- 9908327
TI  - Specific heat of critical films, the Casimir force, and wetting films near
      critical end points.

PMID- 9908328
TI  - Brownian particles in shear flow and harmonic potentials: A study of long-time
      tails.

PMID- 9908329
TI  - Intermittency in dynamical models of turbulence.

PMID- 9908330
TI  - Heat flow and mass diffusion in binary Lennard-Jones mixtures. II.

PMID- 9908332
TI  - Unpredictable convection in a small box: Molecular-dynamics experiments.

PMID- 9908331
TI  - Lattice Boltzmann model for compressible fluids.

PMID- 9908333
TI  - Lattice model for microemulsions in two dimensions.

PMID- 9908334
TI  - Stretching, mode coupling, and the glass transition.

PMID- 9908335
TI  - Prediction of relative permeability in simple porous media.

PMID- 9908336
TI  - Partitioning of polystyrene latex spheres in immiscible critical liquid mixtures.

PMID- 9908337
TI  - Multiparticle simulation for morphological transitions in diffusion-limited
      aggregation.

PMID- 9908338
TI  - Random-sequential adsorption of disks of different sizes.

PMID- 9908339
TI  - Reversible aggregation in an off-lattice particle-coalescence model: Dynamical
      and steady-state scaling behavior.

PMID- 9908341
TI  - Experimental study of colloidal aggregation in two dimensions. II. Kinetic
      aspects.

PMID- 9908340
TI  - Experimental study of colloidal aggregation in two dimensions. I. Structural
      aspects.

PMID- 9908342
TI  - Experimental study of colloidal aggregation in two dimensions. III. Structural
      dynamics.

PMID- 9908343
TI  - Neutral hydrogen in high-temperature pinch plasmas and its influence on the
      ionization dynamics of impurities.

PMID- 9908344
TI  - Possible production of cold plasmas through optical-field-induced ionization.

PMID- 9908345
TI  - Fluid hydrogen at high density: Pressure ionization.

PMID- 9908346
TI  - Proof of a generalized Robinson's theorem on beam damping.

PMID- 9908347
TI  - Spectrum of Schottky noise in ion storage rings.

PMID- 9908348
TI  - Morphology-dependent resonances in a large dielectric sphere: An asymptotic
      calculation using local coordinates.

PMID- 9908350
TI  - Learning in linear neural networks: The validity of the annealed approximation.

PMID- 9908349
TI  - Magnetic energy, multiply connected domains, and force-free fields.

PMID- 9908351
TI  - Learning by maximizing the information transfer through nonlinear noisy neurons
      and "noise breakdown"

PMID- 9908352
TI  - Optimal storage of correlated patterns in neural-network memories.

PMID- 9908353
TI  - Effect of nonlinear dissipation on quantum-activated rate processes in condensed
      phases.

PMID- 9908355
TI  - Exotic behavior of the reaction front in the A+B-->C reaction-diffusion system.

PMID- 9908354
TI  - Homoclinic bifurcation sets of the parametrically driven Duffing oscillator.

PMID- 9908356
TI  - Integrable quantum mappings.

PMID- 9908358
TI  - Kerr-effect investigations in a nematic liquid crystal.

PMID- 9908357
TI  - Microscopic dynamics in liquid alkali metals.

PMID- 9908360
TI  - Dispersion in the radii of gyration of diffusion-limited aggregates.

PMID- 9908359
TI  - Surface tension and evaporation: An empirical relation for water.

PMID- 9908361
TI  - Instability of self-focused optical beams in plasmas: Numerical analysis.

PMID- 9908362
TI  - Enhanced production of negative ions in low-pressure hydrogen and deuterium
      pulsed discharges: Theoretical calculations.

PMID- 9908363
TI  - Comment on "Constraints on biological effects of weak extremely-low-frequency
      electromagnetic fields"

PMID- 9908365
TI  - Erratum: Coherent radiation from spatiotemporally modulated gyrating electron
      beams

PMID- 9908364
TI  - Reply to "Comment on 'Constraints on biological effects of weak extremely-low
      frequency electromagnetic fields' "

PMID- 9908366
TI  - Collective response in globally coupled bistable systems.

PMID- 9908367
TI  - Stochastic resonance for periodically modulated noise intensity.

PMID- 9908368
TI  - Number of distinct sites visited by N particles diffusing on a fractal.

PMID- 9908370
TI  - Structural and dynamical properties of long-range correlated percolation.

PMID- 9908369
TI  - Temporal correlations, universality, and multifractality in a spring-block model
      of earthquakes.

PMID- 9908371
TI  - Physical and numerical experiments on the wave mechanics of classically chaotic
      systems.

PMID- 9908372
TI  - Theory of electronic relaxation in solution: Exact solution for a delta -function
      sink in a parabolic potential.

PMID- 9908373
TI  - Eckhaus instability for traveling waves.

PMID- 9908374
TI  - Observations of the Eckhaus instability in one-dimensional traveling-wave
      convection.

PMID- 9908375
TI  - Focal conic domains with positive Gaussian curvature and saddle-splay rigidity of
      smectic L alpha phases.

PMID- 9908376
TI  - Electron-temperature measurement in laser-produced plasmas by the ratio of
      isoelectronic line intensities.

PMID- 9908377
TI  - Bell's-inequality experiments using independent-particle sources.

PMID- 9908378
TI  - Null result for enhanced neutrino scattering in crystals.

PMID- 9908380
TI  - Spinor structures of the Bethe-Salpeter irreducible kernels.

PMID- 9908379
TI  - Iterative Bogoliubov transformations and anharmonic oscillators.

PMID- 9908381
TI  - Phase-invariant clock hypothesis for accelerating systems.

PMID- 9908382
TI  - Possible interference effect in the Stern-Gerlach phenomenon.

PMID- 9908383
TI  - Ground-state energy for a one-dimensional system of "charged" bosons.

PMID- 9908385
TI  - Casimir effect in absorbing media.

PMID- 9908384
TI  - Basic dynamic properties of the high-order nonlinear Schrodinger equation.

PMID- 9908387
TI  - Wave-packet propagation in momentum space: Calculation of sharp-energy S-matrix
      elements.

PMID- 9908386
TI  - Parametric correlations and diffusion in quantum spectra.

PMID- 9908388
TI  - Characterizing quantum coherence.

PMID- 9908389
TI  - Numerical Hartree-Fock characterization of the metastable 4 Pi u state of the Ne2
      ion.

PMID- 9908390
TI  - Fusion rates from resonant states of td micro.

PMID- 9908391
TI  - Quantities Ts

PMID- 9908392
TI  - Helium doubly excited states with zero angular momentum and electrons located on
      the same side of the nucleus.

PMID- 9908393
TI  - Configuration-interaction and Hylleraas configuration-interaction methods in
      valence-bond theory: Calculation of the nuclear shielding constant for the ground
      state of the hydrogen molecule.

PMID- 9908394
TI  - Electric dipole polarizabilities of atomic valence states.

PMID- 9908395
TI  - Search for the 2S-2P energy difference in muonic 4He ions.

PMID- 9908396
TI  - Energies and relativistic corrections for the Rydberg states of helium:
      Variational results and asymptotic analysis.

PMID- 9908397
TI  - Molecular-orbital description of doubly excited atomic states generalized to
      arbitrary dimension.

PMID- 9908398
TI  - Large multiconfigurational Hartree-Fock calculations on the hyperfine-structure
      constants of the 7Li 2s 2S and 2p 2P states.

PMID- 9908399
TI  - Relativistic effects, correlation, and QED corrections on K alpha transitions in
      medium to very heavy atoms.

PMID- 9908400
TI  - General computational method for two-electron systems.

PMID- 9908401
TI  - Selective population of ionic states produced in photoionization by linearly
      polarized light.

PMID- 9908402
TI  - Circular polarization of the Fe XXV x-ray lines following collisional excitation
      by longitudinally polarized electrons.

PMID- 9908403
TI  - Low-energy electron-impact excitation of the 3,1A2(n--> pi *) states of
      formaldehyde.

PMID- 9908405
TI  - Electron-impact ionization of the tungsten atom.

PMID- 9908404
TI  - Angle-resolved photoelectron spectrometry of atomic chlorine using synchrotron
      radiation.

PMID- 9908406
TI  - Rayleigh scattering of neutron capture gamma rays from lead.

PMID- 9908408
TI  - Calculations of generalized oscillator strength for electron-impact excitations
      of krypton and xenon using a relativistic local-density potential.

PMID- 9908407
TI  - Measurement of a hyperfine-induced spin-exchange frequency shift in atomic
      hydrogen.

PMID- 9908409
TI  - Ion-impact ionization of He targets.

PMID- 9908410
TI  - Time-dependent aspects of electron degradation: Subexcitation electrons in O2-N2
      mixtures.

PMID- 9908411
TI  - Absolute triple differential cross section for ionization of helium near
      threshold.

PMID- 9908413
TI  - Positronium-lithium-ion scattering.

PMID- 9908412
TI  - Threshold electron excitation of Na.

PMID- 9908414
TI  - Nonperturbative treatment of the Thomas mechanism in electron capture.

PMID- 9908416
TI  - Operatorial formulation of multichannel quantum-defect theory.

PMID- 9908415
TI  - K-shell ionization of intermediate-Z elements by 30-MeV/amu H, N, Ne, and Ar
      ions.

PMID- 9908417
TI  - Increase of true double-electron-capture cross sections in slow Xeq+-(Xe,He)
      collisions at very high q.

PMID- 9908418
TI  - Scaling laws governing the multiple scattering of diatomic molecules under
      Coulomb explosion.

PMID- 9908419
TI  - Electron-positron pair creation with capture and ionization in relativistic heavy
      ion collisions by the finite-difference method.

PMID- 9908420
TI  - Al atomic Auger electron emission from low-keV-ion-bombarded Al surfaces.

PMID- 9908421
TI  - Acceleration of convoy electrons by surface wake produced at glancing-angle
      scattering of fast ions from a single-crystal surface.

PMID- 9908422
TI  - Microwave spectroscopy of high-L, n=10 Rydberg states of helium.

PMID- 9908423
TI  - Noble-gas broadening rates for barium transitions involving the metastable 6s5d
      3DJ levels.

PMID- 9908424
TI  - Spurious spectral fluctuations due to missing levels.

PMID- 9908425
TI  - Cyclotron resonance with 10(-)11 resolution: Anharmonic detection and beating a
      coherent drive with the noise.

PMID- 9908426
TI  - Laser cooling of trapped ions in a standing wave.

PMID- 9908427
TI  - Regular and chaotic motions in ion traps: A nonlinear analysis of trap equations.

PMID- 9908428
TI  - Diamagnetic Rydberg atoms and negative-energy Coulomb functions.

PMID- 9908430
TI  - Nonlinear-optical processes in the near-resonant two-photon excitation of xenon
      by femtosecond KrF-excimer-laser pulses.

PMID- 9908429
TI  - Inversionless amplification of a monochromatic field by a three-level medium.

PMID- 9908431
TI  - Frequency spectrum of the signal wave in resonant four-wave mixing induced by
      broad-bandwidth lasers.

PMID- 9908433
TI  - Two-photon double-beam optical bistability in the dispersive regime.

PMID- 9908432
TI  - Optical beams in saturable self-focusing media.

PMID- 9908434
TI  - Phase properties of quantum states of light.

PMID- 9908436
TI  - Quantum correlation between longitudinal-mode intensities in a multimode squeezed
      semiconductor laser.

PMID- 9908435
TI  - Diffraction and focusing of spectral energy in multiphoton processes.

PMID- 9908437
TI  - Generalized linear input-output theory for quantum fluctuations.

PMID- 9908439
TI  - Spatiotemporal dynamics of a unidirectional ring oscillator with photorefractive
      gain.

PMID- 9908438
TI  - Calculations of high-order harmonic-generation processes in xenon at 1064 nm.

PMID- 9908441
TI  - Antiphase dynamics and polarization effects in the Nd-doped fiber laser.

PMID- 9908440
TI  - Squeezed light from conventionally pumped lasers with nonuniform spatial
      structure.

PMID- 9908442
TI  - Radiative and collisional damping effects on efficient population transfer in a
      three-level system driven by two delayed laser pulses.

PMID- 9908443
TI  - Adiabatic four-wave mixing in a strongly driven resonant four-level system:
      Effect of pump depletion.

PMID- 9908444
TI  - Further investigations of the operationally defined quantum phase.

PMID- 9908445
TI  - Reduction in laser-intensity fluctuations by a feedback-controlled output mirror.

PMID- 9908446
TI  - Continuous quantum-nondemolition measurement of photon number.

PMID- 9908447
TI  - Phase properties of real field states: The Garrison-Wong versus Pegg-Barnett
      predictions.

PMID- 9908448
TI  - Pulsed dressed-state lasers.

PMID- 9908449
TI  - Theory of photorefractive phase-conjugate oscillators. I. Isotropic four-wave
      mixing.

PMID- 9908450
TI  - Theory of photorefractive phase-conjugate oscillators. II. Anisotropic four-wave
      mixing.

PMID- 9908451
TI  - Cone emission from laser-pumped two-level atoms. I. Quantum theory of resonant
      light propagation.

PMID- 9908453
TI  - Photoionization of highly charged ions.

PMID- 9908452
TI  - Cone emission from laser-pumped two-level atoms. II. Analytical model studies.

PMID- 9908454
TI  - Exact solution to the time-dependent Schrodinger equation in two dimensions.

PMID- 9908455
TI  - Dielectronic-recombination cross sections and rate coefficients for S3+

PMID- 9908456
TI  - Angular distribution of electrons elastically scattered from hydrogen atoms. II.

PMID- 9908458
TI  - Collision-induced Raman trace spectra of pairs of H2 molecules.

PMID- 9908457
TI  - Relaxed relativistic random-phase-approximation calculations of photoionization
      amplitudes and phases for the 4d subshell of xenon.

PMID- 9908460
TI  - Field-theoretical view of the angular correlation of photons.

PMID- 9908459
TI  - High-precision hyperfine spectroscopy in M1-M1 double-resonance transitions on
      trapped 207Pb+

PMID- 9908461
TI  - Erratum: Synchronization, attractor fission, and attractor fusion in a globally
      coupled laser system

PMID- 9908462
TI  - Erratum: Entangled coherent states

PMID- 9908463
TI  - Quantum irregular spectra: An alternative interpretation from the viewpoint of
      nonlinear dynamics.

PMID- 9908464
TI  - Relativistic many-body perturbation theory applied to n=2 triplet states of
      heliumlike ions.

PMID- 9908465
TI  - Amplitude modulation of atomic wave functions.

PMID- 9908466
TI  - Fractional revivals in the Jaynes-Cummings model.

PMID- 9908467
TI  - Atomic-structure effects in multiphoton ionization of magnesium.

PMID- 9908469
TI  - Performance measures of quantum-phase measurement.

PMID- 9908468
TI  - Grating stimulated echo.

PMID- 9908470
TI  - Two- and three-photon detachment of H- by a weak field.

PMID- 9908471
TI  - Nonperturbative theory of harmonic generation in helium under a high-intensity
      laser field: The role of intermediate resonance and of the ion.

PMID- 9908472
TI  - Dynamic response function and bounds of the susceptibility of a semiclassical gas
      and Kramers-Kronig relations in optic-data inversion.

PMID- 9908473
TI  - Topology changes in fluid membranes.

PMID- 9908474
TI  - Orientational order in random packings of ellipses.

PMID- 9908475
TI  - Local-geometric-projection method for noise reduction in chaotic maps and flows.

PMID- 9908476
TI  - Spiral waves over metal catalysts.

PMID- 9908477
TI  - Bistable chaos. I. Unfolding the cusp.

PMID- 9908478
TI  - Bistable chaos. II. Bifurcation analysis.

PMID- 9908479
TI  - Method to distinguish possible chaos from colored noise and to determine
      embedding parameters.

PMID- 9908480
TI  - Scaling behavior of randomly triangulated self-avoiding surfaces.

PMID- 9908481
TI  - Models of crack propagation.

PMID- 9908483
TI  - Universal classification scheme for the spatial-localization properties of one
      particle states in finite, d-dimensional systems.

PMID- 9908482
TI  - Spatial structure in diffusion-limited two-species annihilation.

PMID- 9908484
TI  - Periodic orbits in quantum standard maps.

PMID- 9908486
TI  - Nonstatistical behavior of higher-dimensional coupled systems.

PMID- 9908485
TI  - Dynamical mechanism for the formation of metastable phases: The case of two
      nonconserved order parameters.

PMID- 9908488
TI  - Freely jointed molecular chain: Dynamical variables, quantization, and
      statistical mechanics.

PMID- 9908487
TI  - Modulational instabilities in discrete lattices.

PMID- 9908489
TI  - Surface roughening and the long-wavelength properties of the Kuramoto-Sivashinsky
      equation.

PMID- 9908490
TI  - Monte Carlo simulation of lattice bosons in three dimensions.

PMID- 9908491
TI  - Asymptotic regime of quantal stochastic and dissipative motion.

PMID- 9908492
TI  - Experimental study of the signal-to-noise ratio of stochastic resonance systems.

PMID- 9908494
TI  - Dynamic properties of liquid cesium near the melting point: A molecular-dynamics
      study.

PMID- 9908493
TI  - Stochastic resonance in a nonlinear system driven by an aperiodic force.

PMID- 9908495
TI  - Self-diffusion in a dilute gas under heat and momentum transport.

PMID- 9908496
TI  - Spatial coherence of homodyne light scattering from particles in a convective
      velocity field.

PMID- 9908497
TI  - Statistical analysis of compressible turbulent shear flows with special emphasis
      on turbulence modeling.

PMID- 9908498
TI  - Exact effective-stress rules in rock mechanics.

PMID- 9908499
TI  - Mass diffusion of atomic fluids in random micropore spaces using equilibrium
      molecular dynamics.

PMID- 9908500
TI  - Sponge phase of surfactant solutions: An unusual dynamic structure factor.

PMID- 9908501
TI  - Polymer diffusion in porous media of fumed silica studied by forced Rayleigh
      scattering.

PMID- 9908502
TI  - Light-scattering investigation of alpha and beta relaxation near the liquid-glass
      transition of the molecular glass Salol.

PMID- 9908504
TI  - Nonmonotonic behavior of a contact angle on approaching critical end points.

PMID- 9908503
TI  - Invasion percolation in a destabilizing gradient.

PMID- 9908505
TI  - Thermodynamic properties of the fluid, fcc, and bcc phases of monodisperse charge
      stabilized colloidal suspensions within the Yukawa model.

PMID- 9908507
TI  - Three-dimensional ballistic deposition at oblique incidence.

PMID- 9908506
TI  - Positron annihilation in xenon: The path-integral approach.

PMID- 9908509
TI  - Study of K alpha absorption structures in a subcritical-density laser-produced
      plasma.

PMID- 9908508
TI  - Continuous mean-field theory of the diffusion-limited-aggregation model.

PMID- 9908510
TI  - Low-frequency fluctuations in plasma magnetic fields.

PMID- 9908511
TI  - Influence of negative ions on the plasma boundary sheath.

PMID- 9908512
TI  - Dielectric tensor and shear-mode dispersion for strongly coupled Coulomb liquids:
      Three-dimensional one-component plasmas.

PMID- 9908514
TI  - Mechanism of resonant interaction of plane ion-acoustic solitons.

PMID- 9908513
TI  - Dielectric tensor and shear-mode dispersion for strongly coupled Coulomb liquids:
      Two-dimensional electron liquid.

PMID- 9908515
TI  - Investigation of the electron plasma component produced by some types of gas
      discharge arc sources.

PMID- 9908517
TI  - Iterative determination of invariant tori for a time-periodic Hamiltonian with
      two degrees of freedom.

PMID- 9908516
TI  - Dynamic properties and the two-point correlation function for electrons in
      localized coherent Langmuir fields.

PMID- 9908518
TI  - Hamilton-Jacobi treatment of second-class constraints.

PMID- 9908519
TI  - Scalar optical beams with helical symmetry.

PMID- 9908520
TI  - Hyperbolic distributions and fractal character of fracture surfaces.

PMID- 9908522
TI  - Analytical calculation of the attractor periods of deterministic sandpiles.

PMID- 9908521
TI  - On the kinetic roughening of vicinal surfaces.

PMID- 9908523
TI  - Branch structures at the steps of the devil's staircase of the sine circle map.

PMID- 9908524
TI  - Unified expression for Fermi and Bose distributions.

PMID- 9908525
TI  - Complex dynamics of a localized target pattern in electrohydrodynamic convection.

PMID- 9908526
TI  - Stability of two-dimensional needle growth.

PMID- 9908527
TI  - Micellar hexagonal phases in lyotropic liquid crystals.

PMID- 9908529
TI  - Identification of intermediate radicals in the CH4 microwave plasma by the Li+
      attachment method.

PMID- 9908528
TI  - Incommensurate periodic configurations in systems with a real order parameter.

PMID- 9908530
TI  - Analytical solution of the Fokker-Planck equation for ions in a magnetic well
      with neutral-beam pumping.

PMID- 9908531
TI  - Theory of free-wave acceleration.

PMID- 9908532
TI  - Experimental test of the inverse free-electron-laser accelerator principle.

PMID- 9908534
TI  - Reply to "Comments on the amplification of intrinsic fluctuations by chaotic
      dynamics"

PMID- 9908533
TI  - Comments on the amplification of intrinsic fluctuations by chaotic dynamics.

PMID- 9908536
TI  - Soliton chaos in the nonlinear Schrodinger equation with spatially periodic
      perturbations.

PMID- 9908535
TI  - Erratum: Collective dynamics in liquid cesium near the melting point

PMID- 9908537
TI  - Dynamic scaling of coupled nonequilibrium interfaces.

PMID- 9908538
TI  - Relations of 1/f and 1/f2 power spectra to self-organized criticality.

PMID- 9908539
TI  - Glass formation in a simple monatomic liquid with icosahedral inherent local
      order.

PMID- 9908541
TI  - Stability limits of spirals and traveling waves in nonequilibrium media.

PMID- 9908540
TI  - Nearest-neighbor distribution functions and mean separation for impenetrable
      particles in one to three dimensions.

PMID- 9908543
TI  - epsilon entropy for a time series of thermal turbulence.

PMID- 9908542
TI  - Transition from confined to extended traveling waves in a convective binary
      mixture.

PMID- 9908544
TI  - Macroscopic dynamics of an isotropic liquid phase containing chiral objects.

PMID- 9908545
TI  - Fractal aggregates and gels in shear flow.

PMID- 9908546
TI  - Conformations of a polyelectrolyte chain.

PMID- 9908547
TI  - Multifractal spectrum of off-lattice three-dimensional diffusion-limited
      aggregation.

PMID- 9908548
TI  - Alternative approach to percolation in microemulsions.

PMID- 9908549
TI  - Evidence against existing x-ray-energy response theories for silicon-surface
      barrier semiconductor detectors.

PMID- 9908550
TI  - Proposed differential-frequency-readout system by hysteretic Josephson junctions.

PMID- 9908551
TI  - Invariants and geometric phase for systems with non-Hermitian time-dependent
      Hamiltonians.

PMID- 9908552
TI  - Half solitons as solutions to the Zakharov-Shabat eigenvalue problem for rational
      reflection coefficient with application in the design of selective pulses in
      nuclear magnetic resonance.

PMID- 9908554
TI  - Critical analysis of the empirical tests of local hidden-variable theories.

PMID- 9908553
TI  - Quantization of second-order Lagrangians: The Fokker-Wheeler-Feynman model of
      electrodynamics.

PMID- 9908555
TI  - Relativistic quantum theory in momentum space for weak and strong coupling.

PMID- 9908556
TI  - Observability of quaternionic quantum mechanics.

PMID- 9908557
TI  - Precise determinations of ionization potentials and EF-state energy levels of H2,
      HD, and D2.

PMID- 9908558
TI  - Hartree-Fock and Roothaan-Hartree-Fock energies for the ground states of He
      through Xe.

PMID- 9908559
TI  - Stability of three-unit-charge systems.

PMID- 9908560
TI  - Core-valence correlation effects on E1 and E2 decay rates in Ca+

PMID- 9908561
TI  - Relativistic calculations of nuclear motional effects in many-electron atoms.

PMID- 9908562
TI  - Relativistic excitation energies and oscillator strengths for the (5s2)1S0-
      >(5s5p)1P1,3P1 transitions in Cd-like ions.

PMID- 9908563
TI  - Optical isotope shifts of stable hafnium atoms in a resonance cell on-line with a
      heavy-ion accelerator.

PMID- 9908564
TI  - Relativistic basis-set calculations for atoms with Fermi nuclei.

PMID- 9908565
TI  - Exchange energy of alkali-metal dimer cations calculated from the atomic
      polarizability with the Holstein-Herring method.

PMID- 9908567
TI  - Dipole density function and evaluation of the oscillator strength of He.

PMID- 9908566
TI  - Kohn-Sham potentials and wave functions from electron densities.

PMID- 9908568
TI  - Accurate screened QED calculations in high-Z many-electron ions.

PMID- 9908569
TI  - Moleculelike metastable states of antiprotonic and mesic helium.

PMID- 9908570
TI  - Angular distributions of ejected electrons from autoionizing 3pnd states of
      magnesium.

PMID- 9908571
TI  - Balslev-Combes theorem within the framework of the finite-matrix approximation.

PMID- 9908572
TI  - Measurement of level-specific dielectronic-recombination cross sections of
      heliumlike Fe XXV.

PMID- 9908573
TI  - Regularities in calculated photoionization cross sections for the halogens.

PMID- 9908574
TI  - Collisional deactivation for K in high-lying 2S and 2D states by H2.

PMID- 9908575
TI  - H- formation from collisional destruction of fast H3+ ions in noble gases.

PMID- 9908576
TI  - Charge transfer of N4+ with atomic hydrogen.

PMID- 9908577
TI  - Green's function for delta -function potentials with a hard core: Application to
      multiphoton photodetachment of negative halogen ions.

PMID- 9908578
TI  - Algebraic rotating-frame approach to electron-molecule scattering: A hybrid
      calculation.

PMID- 9908579
TI  - State-selective capture in collisions of protons with noble gases.

PMID- 9908580
TI  - Absolute total-cross-section measurements for intermediate-energy electron
      scattering on CF4, CClF3, CCl2F2, CCl3F, and CCl4.

PMID- 9908581
TI  - Single-electron capture by 100-1500-keV C+ ions in several atomic and molecular
      targets.

PMID- 9908582
TI  - Theoretical study of nonresonant 3He++4He

PMID- 9908583
TI  - M- and L-shell ionization in near-central collisions of 5.5-MeV/amu 16O ions with
      Mo atoms deduced from theoretical analysis of high-resolution K x-ray spectra.

PMID- 9908585
TI  - Model description for single-electron transfer in slow-ion-H2-molecule
      collisions: Studies for H+, He2+, and C4+ projectiles.

PMID- 9908584
TI  - Dielectronic recombination from high-lying resonance states in H-like silicon,
      calcium, and iron.

PMID- 9908586
TI  - Variational close-coupling calculation for positron-hydrogen scattering at low
      energies.

PMID- 9908587
TI  - Photodetachment cross sections for Li-

PMID- 9908588
TI  - Dissociation of multicharged CO molecular ions produced in collisions with 97-MeV
      Ar14+: Dissociation fractions and branching ratios.

PMID- 9908589
TI  - High-resolution K-shell photoabsorption in formaldehyde.

PMID- 9908591
TI  - Coupled-channels optical calculation of electron-hydrogen resonances.

PMID- 9908590
TI  - Inner-shell photoionization of beryllium.

PMID- 9908593
TI  - Low-energy behavior of few-particle scattering amplitudes in two dimensions.

PMID- 9908592
TI  - Multielectronic excitations near the K edge of argon.

PMID- 9908594
TI  - Algebraic eikonal approach to electron-molecule scattering. I. Generalized
      formalism.

PMID- 9908595
TI  - Algebraic eikonal approach to electron-molecule scattering. II. Rotational
      vibrational excitations.

PMID- 9908596
TI  - Excitation of target Auger-electron emission by the impact of highly charged
      ions: N6+, O7+, and Ne9+ on Pt(110).

PMID- 9908597
TI  - Three-electron systems with inner-shell vacancies.

PMID- 9908598
TI  - Excited states as resonances in the photon-atom continuum and the natural-line
      shape problem.

PMID- 9908599
TI  - Mean-field approach to the algebraic treatment of molecules: Linear molecules.

PMID- 9908601
TI  - Atom cooling by time-dependent potentials.

PMID- 9908600
TI  - Thomas-Fermi model for the C60 molecule.

PMID- 9908602
TI  - Center-of-mass corrections to the electromagnetic transitions of hydrogen atoms
      in strong magnetic fields.

PMID- 9908603
TI  - Unified treatment of high-order perturbation theory for the Stark effect in a two
      and three-dimensional hydrogen atom.

PMID- 9908604
TI  - Calculating the diffusion coefficient for laser cooling of atoms with long-range
      collisions.

PMID- 9908605
TI  - Resonance behavior of a two-level quantum system in a two-frequency field.

PMID- 9908606
TI  - Experimental and theoretical study of the vapor-cell Zeeman optical trap.

PMID- 9908607
TI  - Semiclassical theory of collision-induced loss from optical traps.

PMID- 9908609
TI  - Landau-Zener transition to a decaying level.

PMID- 9908608
TI  - Laser-rf double-resonance spectroscopy in a storage ring.

PMID- 9908610
TI  - Deterministic dynamics of stimulated scattering phenomena with external feedback.

PMID- 9908611
TI  - Interpretation for Rayleigh self-oscillations in a pure sodium vapor driven by
      counterpropagating light beams.

PMID- 9908612
TI  - Effect of bistability and superpositions on quantum statistics in degenerate
      parametric oscillation.

PMID- 9908613
TI  - Application of the displaced oscillator basis in quantum optics.

PMID- 9908614
TI  - Aspherical laser resonators: An analogy with quantum mechanics.

PMID- 9908615
TI  - Effect of the dynamic Stark shift on dipole squeezing in two-photon processes.

PMID- 9908616
TI  - Behavior of spectral lines and degree of spatial coherence in the presence of
      refraction.

PMID- 9908617
TI  - Pair correlations, cascading, and local-field effects in nonlinear optical
      susceptibilities.

PMID- 9908619
TI  - Femtosecond solitons in nonlinear optical fibers: Classical and quantum effects.

PMID- 9908618
TI  - Dark solitary waves in a generalized version of the nonlinear Schrodinger
      equation.

PMID- 9908621
TI  - Radiation from intense-laser-stabilized states of hydrogen.

PMID- 9908620
TI  - Spatiotemporal instabilities in dispersive nonlinear media.

PMID- 9908622
TI  - Suppression of a four-photon resonance by four-wave mixing near an intermediate
      three-photon resonance.

PMID- 9908624
TI  - Time development of photon statistics in fluorescence from single atoms.

PMID- 9908623
TI  - Thresholdless microlaser.

PMID- 9908625
TI  - Schrodinger-cat states at finite temperature: Influence of a finite-temperature
      heat bath on quantum interferences.

PMID- 9908626
TI  - Preferential instability in arrays of coupled lasers.

PMID- 9908627
TI  - Effect of atomic line shape on spatial coherence in mirrorless lasers.

PMID- 9908628
TI  - Quantum-noise limit on optical amplification by two-beam coupling in an atomic
      vapor.

PMID- 9908629
TI  - Quantum-nondemolition measurements using ghost transitions.

PMID- 9908630
TI  - Studies of a 96.9-nm laser in neutral cesium.

PMID- 9908632
TI  - Quantization of the electromagnetic field in dielectrics.

PMID- 9908631
TI  - Strong-field effects of the one-dimensional hydrogen atom in momentum space.

PMID- 9908633
TI  - Asymptotic approximations for the Q function in the Jaynes-Cummings model.

PMID- 9908634
TI  - Dissipation and fluctuation due to foreign-atom collisions: A Langevin-type
      equation approach.

PMID- 9908636
TI  - Interaction of a two-level atom with a cavity mode in the bad-cavity limit.

PMID- 9908635
TI  - Wave-function shock waves.

PMID- 9908637
TI  - Wave-function quantum stochastic differential equations and quantum-jump
      simulation methods.

PMID- 9908638
TI  - Monte Carlo simulation of master equations in quantum optics for vacuum, thermal,
      and squeezed reservoirs.

PMID- 9908639
TI  - Linear input-output method for quantum fluctuations in optical bistability with
      two-level atoms.

PMID- 9908640
TI  - Angular distribution of electrons elastically scattered from water vapor.

PMID- 9908642
TI  - Finite violation of a Bell inequality for arbitrarily large spin.

PMID- 9908641
TI  - Nambu mechanics and its quantization.

PMID- 9908644
TI  - Weakly bound ground states in three-body Coulomb systems with unit charges.

PMID- 9908643
TI  - Many-body-perturbation-theory calculations of the microwave and vibrational
      constants of CaC.

PMID- 9908645
TI  - Self-energy correction to one-electron energy levels in a strong Coulomb field.

PMID- 9908646
TI  - K-shell x-ray production cross sections for low-Z elements (11 <= Z <= 22) by 1
      2.5-MeV 4He ions.

PMID- 9908647
TI  - Line shapes of atomic hydrogen in a plane-cathode abnormal glow discharge.

PMID- 9908648
TI  - Modified resonance amplitudes with strongly correlated channels.

PMID- 9908649
TI  - Use of Coulomb-Sturmian functions in calculating scattering quantities in Coulomb
      like potentials.

PMID- 9908651
TI  - Decay of metastable H atoms in intense excimer lasers.

PMID- 9908650
TI  - Laser-pulse-induced frequency chirp in surface second-harmonic generation.

PMID- 9908652
TI  - Quantum effects versus the semiclassical approximation.

PMID- 9908653
TI  - Propagation and stability of nonlinear surface waves.

PMID- 9908654
TI  - Erratum: Magnetic hyperfine interaction constants and electronic g factors for
      eight atomic states of 103Rh

PMID- 9908655
TI  - Mass as a quantum effect.

PMID- 9908656
TI  - Ca negative-ion binding energy.

PMID- 9908657
TI  - Double photoionization of atomic helium and its isoelectronic partners at x-ray
      energies.

PMID- 9908658
TI  - Strong inhibition effect on secondary-electron emission induced by fast hydrogen
      clusters.

PMID- 9908659
TI  - Density behavior of the depolarized-interaction-induced light-scattering line
      shape in gaseous argon at T=298 K and pressures between 30 and 262 MPa.

PMID- 9908660
TI  - Light-induced vapor jets.

PMID- 9908662
TI  - Hexagonal patterns in optical bistability.

PMID- 9908661
TI  - Observation of multiple-harmonic radiation induced from a gold surface by
      picosecond neodymium-doped yttrium aluminum garnet laser pulses.

PMID- 9908663
TI  - Lasing without inversion in a V system due to trapping of modified atomic states.

PMID- 9908665
TI  - Effects of A desorption on the first-order transition in the A-B2 reaction model.

PMID- 9908664
TI  - Surface tension in the Widom model by low-temperature expansion.

PMID- 9908666
TI  - Thermodynamics, statistical thermodynamics, and computer simulation of crystals
      with vacancies and interstitials.

PMID- 9908667
TI  - Clusters in one-dimensional Poissonian distributions of points: Exact approach.

PMID- 9908668
TI  - Zeros of the Husimi functions of the spin-boson model.

PMID- 9908669
TI  - Transfer dynamics of a quasiparticle in a nonlinear dimer coupled to an intersite
      vibration: Chaos on the Bloch sphere.

PMID- 9908670
TI  - Kinetic roughening in a model of sedimentation of granular materials.

PMID- 9908672
TI  - Planar version of Baym-Kadanoff theory.

PMID- 9908671
TI  - Morphological change of self-affine surfaces to paraboloids with cusps during
      growing processes.

PMID- 9908674
TI  - Method of finding analytical solutions to some nonlinear differential equations
      of dissipative critical dynamics.

PMID- 9908673
TI  - Mechanical models of Maxwell's demon with noninvariant phase volume.

PMID- 9908675
TI  - Quantum dynamics of a damped particle in a tight-binding lattice.

PMID- 9908676
TI  - Investigation of the first-order phase transition in the A-B2 reaction model
      using a constant-coverage kinetic ensemble.

PMID- 9908677
TI  - Quantum dynamics from the Brownian recoil principle.

PMID- 9908678
TI  - Low-coverage kinetics of correlated sequential adsorption.

PMID- 9908679
TI  - Monte Carlo simulations in the isoenthalpic-isotension-isobaric ensemble.

PMID- 9908680
TI  - Spectral autocorrelation function in the statistical theory of energy levels.

PMID- 9908681
TI  - Scaling structure in simple screening models for columnar growth.

PMID- 9908682
TI  - Algebraic decay and fluctuations of the decay exponent in Hamiltonian systems.

PMID- 9908684
TI  - Nonlinear dynamics of a breakable chain at threshold: Large-N results.

PMID- 9908683
TI  - Generation of spatiotemporal colored noise.

PMID- 9908685
TI  - Earthquake dynamics driven by a viscous fluid.

PMID- 9908686
TI  - Quantum third virial coefficient of a fractional-statistics gas.

PMID- 9908687
TI  - Alternative to the Pomraning-Eddington approach to radiative transfer.

PMID- 9908688
TI  - Localization of a quantum-mechanical particle in classical simple fluids.

PMID- 9908689
TI  - Neutron-diffraction study of liquid hydrogen iodide.

PMID- 9908691
TI  - Pattern formation in convection of rotating fluids with broken vertical symmetry.

PMID- 9908690
TI  - Theory of the electron distribution function in a Lorentz gas at high E/n0.

PMID- 9908692
TI  - Dimension of the carrier of turbulence: Intermittency in fluid mechanics.

PMID- 9908694
TI  - Planform selection in rotating convection: Hexagonal symmetry.

PMID- 9908693
TI  - Comparison of steady-state and strongly chaotic thermal convection at high
      Rayleigh number.

PMID- 9908695
TI  - Counterbalanced interaction locality of developed hydrodynamic turbulence.

PMID- 9908696
TI  - Effects of additive noise at the onset of Rayleigh-Benard convection.

PMID- 9908697
TI  - Nonlinear surface-wave excitations in the Benard-Marangoni system.

PMID- 9908698
TI  - Chaotic interface dynamics: A model with turbulent behavior.

PMID- 9908699
TI  - Two-field theory of incompressible-fluid turbulence.

PMID- 9908700
TI  - Molecular-dynamics simulation of compressible fluid flow in two-dimensional
      channels.

PMID- 9908701
TI  - Fractal level sets and multifractal fields in direct simulations of turbulence.

PMID- 9908702
TI  - Surface-directed spinodal decomposition in a two-dimensional model.

PMID- 9908703
TI  - Ginzburg-Landau theory of oil-water-surfactant mixtures.

PMID- 9908704
TI  - High-frequency dielectric behavior of a ferroelectric liquid crystal near the
      smectic-C*-smectic-A phase transition.

PMID- 9908705
TI  - Self-induced stimulated light scattering in nematic liquid crystals: Theory and
      experiment.

PMID- 9908707
TI  - Pretransitional phenomena and pinning in liquid-crystalline blue phases.

PMID- 9908706
TI  - Natural convection, Taylor dispersion, and diagenesis in a tilted porous layer.

PMID- 9908709
TI  - Dynamics of labyrinthine pattern formation in magnetic fluids.

PMID- 9908708
TI  - Critical behavior of the self-diffusion coefficient in a binary fluid.

PMID- 9908710
TI  - Thermal attenuation and dispersion of sound in a periodic emulsion.

PMID- 9908711
TI  - Instability of the fluid pair structure and the freezing density of liquids.

PMID- 9908712
TI  - Structure of polymer chains end-grafted on an interacting surface.

PMID- 9908714
TI  - Mode-coupling theory of the stress-tensor autocorrelation function of a dense
      binary fluid mixture.

PMID- 9908713
TI  - Theory of nematic surface ordering via a Berezinskii-Kosterlitz-Thouless phase
      transition.

PMID- 9908715
TI  - Secondary instabilities in electroconvection in nematic liquid crystals.

PMID- 9908717
TI  - Isotropic-nematic transition in shear flow: State selection, coexistence, phase
      transitions, and critical behavior.

PMID- 9908716
TI  - Anchoring structure of liquid-crystal monolayers on polyimide Langmuir-Blodgett
      films observed by scanning tunneling microscopy.

PMID- 9908719
TI  - Dynamical properties of hard-sphere suspensions.

PMID- 9908718
TI  - Macroscopic theory of wetting in a wedge.

PMID- 9908720
TI  - Long-time self-diffusion coefficients of suspensions.

PMID- 9908721
TI  - Study of the critical behavior of an irreversible phase transition in the A+B-
      >AB reaction with B desorption on a fractal surface.

PMID- 9908722
TI  - Phase instability and local dynamics in directional solidification.

PMID- 9908724
TI  - Parametric control of microstructures in directional solidification.

PMID- 9908723
TI  - Calculation of the fractal dimension of diffusion-limited aggregation by the
      renormalization-group approach in an arbitrary Euclidean dimension d.

PMID- 9908725
TI  - Symmetry-breaking bifurcations in one-dimensional excitable media.

PMID- 9908726
TI  - Irreversible aggregation kinetics: Power-law exponents from series.

PMID- 9908727
TI  - Aggregation frequencies of fractal aggregates.

PMID- 9908728
TI  - Spinodal decomposition between closely spaced plates.

PMID- 9908729
TI  - Dynamics of picosecond-laser-pulse plasmas determined from the spectral shifts of
      reflected probe pulses.

PMID- 9908730
TI  - Stopping of multicharged ions in dense and fully ionized hydrogen.

PMID- 9908731
TI  - Nonlinear dynamics of driven relativistic electron plasma waves.

PMID- 9908733
TI  - Thomas-Fermi molecular dynamics.

PMID- 9908732
TI  - Effect of the small-scale auxiliary laser spots on the 3 omega 0/2 harmonic
      emission.

PMID- 9908734
TI  - Effect of a dielectric medium on spontaneous radiation in a uniform magnetic
      field: Higher harmonics and the helical C-caronerenkov effect.

PMID- 9908735
TI  - Measuring the Wigner rotation with electron beams.

PMID- 9908736
TI  - Unified single-particle theory of free-electron-maser amplifiers.

PMID- 9908737
TI  - Radiation into transverse electric modes of rectangular waveguides from
      spatiotemporally modulated gyrating electron beams.

PMID- 9908738
TI  - Beam-breakup instability in anharmonic ion-focused-regime channels.

PMID- 9908739
TI  - Transverse wake fields in dielectric wake-field accelerators.

PMID- 9908740
TI  - Relaxation of energy from the transverse to the longitudinal direction of a cold
      ion string in a storage ring.

PMID- 9908741
TI  - Spin-orbit interaction of a photon in an inhomogeneous medium.

PMID- 9908742
TI  - Real and imaginary tests of the Lorentz-Dirac equation.

PMID- 9908743
TI  - Resonant kink-impurity interactions in the phi4 model.

PMID- 9908744
TI  - Learning in neural networks with local minima.

PMID- 9908745
TI  - Ion pores in biological membranes as self-organized bistable systems.

PMID- 9908747
TI  - Generalization in an analog neural network.

PMID- 9908746
TI  - Initial events of protein folding from an information-processing viewpoint.

PMID- 9908748
TI  - Experimental observation of stochastic resonance in a magnetoelastic ribbon.

PMID- 9908750
TI  - Effect of edges on random sequential adsorption on a lattice.

PMID- 9908749
TI  - Fluctuations in the time periods of a model chaotic system.

PMID- 9908752
TI  - Hybrid topological defects in nonequilibrium systems.

PMID- 9908751
TI  - Spiral-core meandering in excitable media.

PMID- 9908753
TI  - Chaos due to homoclinic and heteroclinic orbits in two coupled oscillators with
      nonisochronism.

PMID- 9908754
TI  - Method for identification of the core of structural transformations in atomistic
      computer models.

PMID- 9908755
TI  - Slip length in a dilute gas.

PMID- 9908756
TI  - Finite-size-scaling derivation of the Widom critical-exponent relation for
      surface tension.

PMID- 9908757
TI  - Selection of interfacial velocity in the presence of multiple relaxation rates.

PMID- 9908758
TI  - Magnetohydrodynamics for electron-positron plasmas.

PMID- 9908759
TI  - Algebraic decay of correlations in neural networks.

PMID- 9908760
TI  - Comment on "Solutions of the telegrapher's equation in the presence of traps"

PMID- 9908761
TI  - Reply to "Comment on 'Solutions of the telegrapher's equation in the presence of
      traps' "

PMID- 9908762
TI  - Correlation function in stochastic periodically driven instabilities.

PMID- 9908764
TI  - Spanning trees in two dimensions.

PMID- 9908763
TI  - Critical behavior in coupled nonlinear systems.

PMID- 9908765
TI  - Statistical signatures of self-organization.

PMID- 9908766
TI  - Surface fluctuations and criticality in a class of one-dimensional sandpile
      models.

PMID- 9908767
TI  - Numerical study of pattern formation following a convective instability in non
      Boussinesq fluids.

PMID- 9908768
TI  - Surface-directed spinodal decomposition: Phenomenology and numerical results.

PMID- 9908769
TI  - Correlations between surface and bulk liquid-crystal alignment observed with
      optical second-harmonic generation.

PMID- 9908771
TI  - Analytical treatment for parity breaking in eutectic growth.

PMID- 9908770
TI  - Surface-induced phase transition in normal alkane fluids.

PMID- 9908772
TI  - Growth of fingers at a driven three-phase contact line.

PMID- 9908774
TI  - Coarsening and the mean shape of three-dimensional dendritic crystals.

PMID- 9908773
TI  - Two-dimensional dendritic growth in Langmuir monolayers of D-myristoyl alanine.

PMID- 9908775
TI  - Electron distribution function in an intense femtosecond laser field.

PMID- 9908776
TI  - Mechanisms of efficiency enhancement in gyrotron backward-wave oscillators with
      tapered magnetic fields.

PMID- 9908777
TI  - Remote multimode feedback stabilization of plasma instabilities.

PMID- 9908778
TI  - Computation of the fraction of RNA sequences that fold sequentially into a unique
      free-energy minimum.

PMID- 9908779
TI  - Non-Abelian geometric phase and generalized invariant method.

PMID- 9908780
TI  - Berry's phase for anharmonic oscillators.

PMID- 9908781
TI  - Unique Bell state.

PMID- 9908783
TI  - Bell inequalities with a magnitude of violation that grows exponentially with the
      number of particles.

PMID- 9908782
TI  - Generalized Bohr-Sommerfeld rule for quartic oscillators.

PMID- 9908785
TI  - Condition for a bivariate normal probability distribution in phase space to be a
      quantum state.

PMID- 9908784
TI  - Alternative method of evaluating the coherent-state propagator.

PMID- 9908787
TI  - Oscillator strengths for S-P and P-D transitions in heliumlike ions.

PMID- 9908786
TI  - Higher-order relativistic corrections to the polarization energies of helium
      Rydberg states.

PMID- 9908788
TI  - Calculation of some integrals for the atomic three-electron problem.

PMID- 9908790
TI  - Calculations of the ground-state energies of the helium atom and H2+ molecular
      ion based on the Hermite-Gaussian functions.

PMID- 9908789
TI  - Regional virial theorem in density-functional theory.

PMID- 9908791
TI  - Summation methods for dimensional perturbation theory.

PMID- 9908792
TI  - Nonrelativistic Lamb shift for a nonadiabatic many-particle system: An
      application to the dt micro ion.

PMID- 9908793
TI  - General theoretical approach to Coulombic three-body systems by the
      hyperspherical formalism.

PMID- 9908794
TI  - Systematic approximations to the optimized effective potential: Application to
      orbital-density-functional theory.

PMID- 9908795
TI  - Single-configuration descriptions of atomic ground and excited states: Ground
      states of He, Li, and Be.

PMID- 9908796
TI  - Time-dependent gauge-invariant approach to the calculation of dynamic
      hyperpolarizabilities: Application to FH and LiH.

PMID- 9908797
TI  - Many-body perturbation-theory formulas for energy levels of excited states of
      closed-shell atoms.

PMID- 9908798
TI  - Single-channel quantum-defect theory for the description of doubly excited states
      of helium.

PMID- 9908800
TI  - Semiclassical description of dipole matrix elements for arbitrary nl-->n'l'
      transitions in nonhydrogenic ions.

PMID- 9908799
TI  - Semiclassical energy levels and the corresponding potentials in nonhydrogenic
      ions.

PMID- 9908801
TI  - Inelastic electron-electron interaction in the projectile-electron-loss
      probability.

PMID- 9908802
TI  - Technique for the evaluation of double excitation of atoms by fast charged
      particles.

PMID- 9908803
TI  - Exact calculation of the second-order Born terms for exotic-atom formation into
      excited states.

PMID- 9908804
TI  - Distorted atomic-orbital expansion for slow ion-atom collisions.

PMID- 9908806
TI  - Inner-valence states of N2+ studied by uv photoelectron spectroscopy and
      configuration-interaction calculations.

PMID- 9908807
TI  - Excitation and ionization processes in slow collisions of ground-state and
      excited hydrogen atoms with protons.

PMID- 9908805
TI  - Double ionization of helium by high-velocity U90+ ions.

PMID- 9908809
TI  - Velocity dependence of electron-capture partial cross sections and alignment in
      low-energy collisions of Ne8+ and Ar8+ with atomic Na.

PMID- 9908808
TI  - Single-photon double ionization of He and Ne.

PMID- 9908810
TI  - Five-photon ionization of atomic hydrogen at wavelengths around the threshold for
      four-photon ionization.

PMID- 9908811
TI  - Threshold effects and photoelectron spectra in model-system descriptions of
      photodetachment.

PMID- 9908813
TI  - Multiple electron transfer in slow Ne9+-Ne collisions.

PMID- 9908812
TI  - Plane-wave and common-translation-factor treatments of He2++H collisions at high
      velocities.

PMID- 9908814
TI  - Angularly resolved Auger rates of LiF and HF.

PMID- 9908815
TI  - Resonance-enhanced multiphoton-ionization photoelectron spectroscopy of np and nf
      Rydberg states of atomic nitrogen.

PMID- 9908816
TI  - Electron-impact cross sections for multiple ionization of Kr and Xe.

PMID- 9908818
TI  - Single and double ionization in 300-keV H++He collisions at small impact
      parameters.

PMID- 9908817
TI  - Dielectric-sphere-couple model for noble-gas pair polarizability.

PMID- 9908819
TI  - Positron trapping in an electrostatic well by inelastic collisions with nitrogen
      molecules.

PMID- 9908820
TI  - Reexamination of the Li+-He interaction potential.

PMID- 9908822
TI  - Validity of the independent-processes and isolated-resonance approximations for
      electron-ion recombination.

PMID- 9908821
TI  - Exchange effects in electron-impact ionization of atomic hydrogen.

PMID- 9908823
TI  - High-resolution measurement of dielectronic recombination of lithiumlike Cu26+

PMID- 9908824
TI  - Fusion yields for carbon-cluster impact on CD2 targets.

PMID- 9908826
TI  - Electronic energy loss for helium channeling in silicon.

PMID- 9908825
TI  - Stopping power of large homonuclear clusters: Influence of cluster structure.

PMID- 9908827
TI  - Stopping power and ranges of fast ions in heavy elements.

PMID- 9908828
TI  - Laser-rf double-resonance measurements of the hyperfine structure in 49Ti II.

PMID- 9908829
TI  - Rotational spectrum of HD perturbed by He or Ar gases: The effects of
      rotationally inelastic collisions on the interference between allowed and
      collisionally induced components.

PMID- 9908831
TI  - Augmented long-range attraction in collisions involving a Rydberg atom.

PMID- 9908830
TI  - Partial widths of the He- 2S two-electron ionization ladder resonances.

PMID- 9908832
TI  - Collective emission in a resonant cavity in the dependence on an external
      electric field.

PMID- 9908834
TI  - Precise Stark-effect investigations of the lithium D1 and D2 lines.

PMID- 9908833
TI  - Energy levels of the hydrogen atom in arbitrary magnetic fields obtained by using
      B-spline basis sets.

PMID- 9908835
TI  - Numerical experiments in semiclassical laser-cooling theory of multistate atoms.

PMID- 9908836
TI  - Electric-field dependence of E1 transitions between highly excited hydrogen Stark
      sublevels.

PMID- 9908837
TI  - Above-threshold-dissociation dynamics of H2+ with short intense laser pulses.

PMID- 9908838
TI  - Phase-noise squeezing in electromagnetically induced transparency.

PMID- 9908839
TI  - Minimum-uncertainty states, a two-photon system, and quantum-group symmetry.

PMID- 9908840
TI  - Dynamics of generalized photonic fields interacting with atoms.

PMID- 9908841
TI  - Two-peak passage-time distributions in transient CO2 lasers near threshold.

PMID- 9908842
TI  - Comparative study of four-wave mixing in chaotic and phase-diffusing fields.

PMID- 9908844
TI  - Effect of phase-conjugate feedback on the noise characteristics of semiconductor
      lasers.

PMID- 9908843
TI  - Generation of squeezing for a charged oscillator and for a charged particle in a
      time-dependent electromagnetic field.

PMID- 9908845
TI  - Multipulse photon echoes in LaF3:Pr3+

PMID- 9908846
TI  - Fluorescence spectrum of a two-level atom interacting with a quantized field in a
      Kerr-like medium.

PMID- 9908847
TI  - Quantum-field model of the injected atomic beam in the micromaser.

PMID- 9908849
TI  - Intensity correlations of multimode gas lasers.

PMID- 9908848
TI  - Theory of atomic excitation and ionization by ultrashort laser pulses.

PMID- 9908850
TI  - One-atom lasers.

PMID- 9908851
TI  - Two-dimensional optical lattices in a CO2 laser.

PMID- 9908852
TI  - General theory of temperature-dependent ultrafast transient hole burning.

PMID- 9908854
TI  - Variationally stable treatment of two- and three-photon detachment of H-
      including electron-correlation effects.

PMID- 9908853
TI  - Analysis of pumping mechanisms affecting the gain of the J=0-1 and J=2-1 lines in
      neonlike selenium.

PMID- 9908855
TI  - Stability analysis of stationary nonlinear guided waves in self-focusing and self
      defocusing Kerr-like layered media.

PMID- 9908856
TI  - Systematic description of laser phase by linearized Ito equations.

PMID- 9908857
TI  - Theoretical explanation of the first experimentally observed laser without
      inversion in a two-level scheme.

PMID- 9908859
TI  - Theoretical study of a laser with injected signal. II. Periodic perturbation.

PMID- 9908858
TI  - Theoretical study of a laser with injected signal. I. Analytical results on the
      dynamics.

PMID- 9908860
TI  - Effect of detuning on deep squeezing of coherent light in the Jaynes-Cummings
      model.

PMID- 9908861
TI  - Squeezing of coherent light by repeated interaction with atoms.

PMID- 9908862
TI  - Covariance and uniqueness of the canonical fermion coherent state.

PMID- 9908864
TI  - Statistical properties of resonances in two-dimensional quantum-mechanical point
      scattering.

PMID- 9908863
TI  - Self-adjoint extensions of the Hamiltonian for a charged particle in the presence
      of a thread of magnetic flux.

PMID- 9908865
TI  - Modified shifted large-N approach to the Morse oscillator.

PMID- 9908866
TI  - Computation of the second-order correlation energies of Ne using a finite-element
      method.

PMID- 9908867
TI  - Vibrationally resolved states in the HS fragment studied by means of electron
      excited Auger spectroscopy.

PMID- 9908868
TI  - Back rotation of complex rotated resonance wave functions: A numerical study.

PMID- 9908869
TI  - Transmittance for wave-packet scattering.

PMID- 9908870
TI  - Determination of complex scattering amplitudes in low-energy elastic electron
      sodium scattering.

PMID- 9908872
TI  - Hartree-Fock investigations of the structure of Sb4 clusters.

PMID- 9908873
TI  - Strong squeezing by repeated frequency jumps.

PMID- 9908871
TI  - Multielectron transitions in x-ray absorption of krypton.

PMID- 9908874
TI  - Instability threshold for an array of coupled semiconductor lasers.

PMID- 9908875
TI  - Squeezed states and the Franck-Condon overlap.

PMID- 9908877
TI  - Criterion for antibunching according to population monitoring of cavity
      radiation.

PMID- 9908876
TI  - Moment problem for a density matrix and a biorthogonal set of operator bases.

PMID- 9908878
TI  - Theory of surface-emitting second-harmonic generation from optically trapped
      microspheres.

PMID- 9908879
TI  - Comment on "Differential equation for the spherical dipole matrix elements of
      hydrogen"

PMID- 9908880
TI  - Reply to "Comment on 'Differential equation for the spherical dipole matrix
      elements of hydrogen' "

PMID- 9908881
TI  - Dynamic dipole nature of the planetary atom states.

PMID- 9908882
TI  - Determination of the hyperfine structure of H2+( nu =0, R=1) by microwave
      spectroscopy of high-L n=27 Rydberg states of H2.

PMID- 9908883
TI  - Spin coupling constants and hyperfine transition frequencies for the hydrogen
      molecular ion.

PMID- 9908884
TI  - Local exchange-correlation functional: Numerical test for atoms and ions.

PMID- 9908885
TI  - Reexamination of an anomaly in near-threshold pair production.

PMID- 9908886
TI  - Evidence for resonances and absorption effects in positron-krypton differential
      elastic-scattering measurements.

PMID- 9908887
TI  - Trajectory-interference effects in ion-atom collisions.

PMID- 9908889
TI  - Photon wave packets and spontaneous decay in a cavity.

PMID- 9908888
TI  - Interplay between above-threshold multiphoton detachment and higher-harmonic
      generation.

PMID- 9908890
TI  - Ionization rates of H2+ in an intense laser field by numerical integration of the
      time-dependent Schrodinger equation.

PMID- 9908891
TI  - Quantum phase distributions and quasidistributions.

PMID- 9908892
TI  - Phase diffusion and continuous quantum measurements in the micromaser.

PMID- 9908893
TI  - Semiclassical treatment of avoided crossings in the quadratic Zeeman spectrum of
      hydrogen.

PMID- 9908894
TI  - Effects of saturation in the transient process of a dye laser. III. The case of
      colored noise with large and small correlation time.

PMID- 9908895
TI  - Exact solutions of the Schrodinger equation for some quantum-mechanical many-body
      systems.

PMID- 9908897
TI  - Tunneling-time probability distribution.

PMID- 9908896
TI  - Bell theorem without inequalities for two spinless particles.

PMID- 9908898
TI  - Interpretation of geometric phase via geometric distance and length during cyclic
      evolution.

PMID- 9908899
TI  - Modified Riccati approach to partially solvable quantum Hamiltonians. III.
      Related families of Poschl-Teller potentials.

PMID- 9908901
TI  - Quantum fluctuation and phase transition in a harmonic two-electron atomic model
      with variable dimensionality.

PMID- 9908900
TI  - Propagator of the general driven time-dependent oscillator.

PMID- 9908902
TI  - Radiative lifetimes of the 6s8p 1P1 and near-resonant states in barium.

PMID- 9908904
TI  - Relativistic coupled-cluster calculations for open-shell atoms.

PMID- 9908903
TI  - Collinear laser-beam-ion-beam measurement of the mean lifetime of the Ar II 4p'
      2F degrees7/2 level.

PMID- 9908905
TI  - Universal Gaussian basis set for accurate ab initio /P relat ivistic Dirac-Fock
      calculations.

PMID- 9908906
TI  - Photoionization cross section of the 4p55d

PMID- 9908907
TI  - v-representability for noninteracting systems.

PMID- 9908908
TI  - Ultraviolet transition probabilities in N II.

PMID- 9908909
TI  - Self-consistent calculations of atomic properties using self-interaction-free
      exchange-only Kohn-Sham potentials.

PMID- 9908910
TI  - Autoionization resonances in the photoionization of the 3s23p5 2P degrees ground
      state of chlorine.

PMID- 9908911
TI  - Symmetric double charge exchange in fast collisions of bare nuclei with
      heliumlike atomic systems.

PMID- 9908912
TI  - Distorted-wave models for single-electron capture from molecular targets by the
      impact of bare ions.

PMID- 9908913
TI  - Procedures for improving a relativistic distorted-wave approach for excitation of
      ions by electron impact.

PMID- 9908914
TI  - Ionization and pair creation in relativistic heavy-ion collisions.

PMID- 9908915
TI  - Photoionization of the barium 6s6p 1P degrees1 state: Comparison of theory and
      experiment including hyperfine-depolarization effects.

PMID- 9908916
TI  - Target-atomic-number-dependent oscillations of equilibrium charge-state
      distributions of 50-500-keV/u hydrogen and boron emerging from solids.

PMID- 9908917
TI  - Ba(6s6p P11,mj)-->Ba(6s6p P32,mj') Zeeman cross sections in single collisions
      with N2, O2, and H2.

PMID- 9908919
TI  - Coupled-Sturmian treatment of electron transfer and ionization in proton-carbon
      collisions.

PMID- 9908918
TI  - Polarization and correlation effects in elastic electron-Li2 scattering.

PMID- 9908920
TI  - Ab initio calculation of scattering length and cross section at very low energies
      for electron-argon scattering.

PMID- 9908921
TI  - Single-, double-, and triple-photoionization cross sections of carbonyl sulfide
      (OCS) and ionic fragmentation of OCS+, OCS2+, and OCS3+

PMID- 9908922
TI  - Formation and mean lifetime of the metastable doubly charged rare-gas dimer
      NeAr2+

PMID- 9908924
TI  - Angle-differential and momentum-transfer cross sections for low-energy electron
      Cs scattering.

PMID- 9908923
TI  - Relative photoionization and photodetachment cross sections for particular fine
      structure transitions with application to Cl 3s-subshell photoionization.

PMID- 9908925
TI  - Spin-dependent observables in electron-sodium scattering calculated using the
      coupled-channel optical method.

PMID- 9908926
TI  - Track-depth-resolved dynamics of helium excimers along 4-MeV/amu N-ion tracks in
      near-liquid and liquid helium.

PMID- 9908927
TI  - Inconsistent K-L x-ray angular correlations in uranium.

PMID- 9908928
TI  - Collisional modification of the atomic-Na 3s 2S1/2-5s 2S1/2 two-color two-photon
      polarization spectrum.

PMID- 9908929
TI  - Quantum-dynamical semigroup generators for proton-spin relaxation in water.

PMID- 9908930
TI  - High-resolution measurements of near-edge resonances in the core-level
      photoionization spectra of SF6.

PMID- 9908932
TI  - Structure and rearrangements of small trapped-ion clusters.

PMID- 9908931
TI  - Stark-broadening measurements of 3d-->nf transitions in lithiumlike and
      heliumlike ions.

PMID- 9908933
TI  - Second-order corrections to the wave functions of a Coulomb-field electron in a
      weak uniform harmonic electric field.

PMID- 9908934
TI  - Atomic-position resolution by quadrature-field measurement.

PMID- 9908935
TI  - Atoms in strong crossed electric and magnetic fields: Evidence for states with
      large electric-dipole moments.

PMID- 9908936
TI  - Photon-correlation detection of ion-oscillation frequencies in quadrupole ion
      traps.

PMID- 9908937
TI  - How to reset an atom after a photon detection: Applications to photon-counting
      processes.

PMID- 9908938
TI  - Spin-polarizing 3He nuclei with an arc-lamp-pumped neodymium-doped lanthanum
      magnesium hexaluminate laser.

PMID- 9908940
TI  - Monte Carlo simulation of field fluctuations in strongly driven resonant
      transitions.

PMID- 9908939
TI  - NMR calibration of optical measurement of nuclear polarization in 3He.

PMID- 9908941
TI  - Lasing without or with inversion in a closed four-level system.

PMID- 9908942
TI  - Mode-mode interaction for a CO2 laser with imperfect O(2) symmetry.

PMID- 9908943
TI  - Spectral correlations in resonance fluorescence.

PMID- 9908944
TI  - Nonlinear selective reflection in cascade three-level atomic systems.

PMID- 9908945
TI  - Velocity-dependent collision rates from light-induced drift experiments: C2H4
      noble-gas mixtures.

PMID- 9908946
TI  - Quantum-optical version of Cramer's theorem.

PMID- 9908947
TI  - Resonant diffraction mechanism, nonreciprocity, and lock-in in the ring-laser
      gyroscope.

PMID- 9908949
TI  - Coherent multiphoton exchange between a neutron and an oscillating magnetic
      field.

PMID- 9908950
TI  - Photon-number measurements with cold atoms.

PMID- 9908948
TI  - Macroscopic quantum superposition states in nondegenerate parametric oscillation.

PMID- 9908952
TI  - Quantum-mechanical vacuum Rabi-oscillation frequency and the classical effective
      Rabi field.

PMID- 9908951
TI  - Selective excitation via the continuum and suppression of ionization.

PMID- 9908953
TI  - Mode evolution in optical resonators with a radial gain profile.

PMID- 9908954
TI  - Quantum statistics of the light generated by phase-conjugate resonators.

PMID- 9908955
TI  - Inversionless laser from a closed multilevel system.

PMID- 9908956
TI  - Photon statistics of superposition states in phase-sensitive reservoirs.

PMID- 9908957
TI  - Effect of finite atomic lifetimes on the generation of nonclassical states in
      micromasers.

PMID- 9908959
TI  - Quantum-noise reduction in a driven cavity with feedback.

PMID- 9908958
TI  - Separation and superposition of atomic wave packets by reflection and
      transmission by an optical ripple mirror.

PMID- 9908960
TI  - Eavesdropping using quantum-nondemolition measurements.

PMID- 9908961
TI  - Quantum theory of field-quadrature measurements.

PMID- 9908963
TI  - Spurious velocity dependence of free-space spontaneous emission.

PMID- 9908962
TI  - Quantum-nondemolition determination of an atomic state via the optical Stern
      Gerlach effect.

PMID- 9908964
TI  - Multiphoton transitions in a strong field: Inclusion of the photon momentum.

PMID- 9908965
TI  - Quantum field theory on curved low-dimensional space embedded in three
      dimensional space.

PMID- 9908966
TI  - Dynamic Lie-algebra structure of a quantum system and the Aharonov-Anandan phase.

PMID- 9908967
TI  - Rydberg states of helium: Some further small corrections.

PMID- 9908968
TI  - Comparisons of the QED and relativistic parts of the triplet-state energies in
      the heliumlike sequence.

PMID- 9908969
TI  - Measurements of saturation broadening of the Cu 5s' 4D5/2 autoionization level by
      the pulsed optogalvanic technique.

PMID- 9908970
TI  - Widths of the doubly excited resonances of two-electron atoms below the n=2
      threshold.

PMID- 9908971
TI  - Double- and single-electron capture in He2++H2 collisions in the energy range
      from 50 eV to 2 keV.

PMID- 9908972
TI  - Extended Simons-Parr-Finlan approach to the analytical calculation of the
      rotational-vibrational energy of diatomic molecules.

PMID- 9908973
TI  - Free-free transitions in a bichromatic laser field.

PMID- 9908974
TI  - Intense-field scattering and capture of an electron by a model atom.

PMID- 9908975
TI  - One- and two-photon Jaynes-Cummings models as sources of sub-Poissonian fields by
      chaotic pumping.

PMID- 9908976
TI  - Berry's phase in quantum optics.

PMID- 9908977
TI  - Laser-assisted inelastic x-ray scattering as a tool for determination of the
      length of ultrafast x-ray pulses.

PMID- 9908978
TI  - Generalized multimode squeezed states.

PMID- 9908980
TI  - Erratum: General evaluation of atomic electron-repulsion integrals in orbital
      methods without using a series representation for r12-1

PMID- 9908979
TI  - Bistability and chaos in an injection-locked semiconductor laser.

PMID- 9908981
TI  - Inelastic electron-dipole-molecule scattering at sub-milli-electron-volt
      energies: CH3I and CH2Br2.

PMID- 9908982
TI  - Momentum-transfer dependence of S 2p excitations of sulfur hexafluoride by angle
      resolved electron-energy-loss spectroscopy.

PMID- 9908983
TI  - Evidence for significant backscattering in near-threshold electron-impact
      excitation of Ar7+(3s-->3p).

PMID- 9908984
TI  - "Left-right asymmetry" in H(2p) charge capture from laser-oriented Na(3p).

PMID- 9908986
TI  - Image acceleration of multiply charged ions by metallic surfaces.

PMID- 9908985
TI  - High-energy behavior of the double photoionization of helium from 2 to 12 keV.

PMID- 9908987
TI  - Squeezing of thermal and quantum fluctuations: Universal features.

PMID- 9908988
TI  - Wave collapse and optical-pulse compression.

PMID- 9908989
TI  - Photon counting, quantum phase, and phase-space distributions.

PMID- 9908990
TI  - Harmonic generation in the Kramers-Henneberger stabilization regime.

PMID- 9908991
TI  - Principle of inversion in atomic systems subjected to multiple coherent fields.

PMID- 9908992
TI  - Small-signal spectrum focusing using a strong nonuniform pumping beam.

PMID- 9908993
TI  - High-angular-momentum states as population traps in multiphoton ionization.

PMID- 9908994
TI  - Population trapping in Kr and Xe in intense laser fields.

PMID- 9908995
TI  - Atomic supersymmetry and the Stark effect.

PMID- 9908996
TI  - Optimally controlled quantum molecular dynamics: A perturbation formulation and
      the existence of multiple solutions.

PMID- 9908997
TI  - Quasiexactly solvable problems in the path-integral formalism.

PMID- 9908998
TI  - Algebraic scattering theory and the geometric phase.

PMID- 9908999
TI  - Optimally controlled quantum molecular dynamics: The effect of nonlinearities on
      the magnitude and multiplicity of control-field solutions.

PMID- 9909000
TI  - Variational method for the free-energy approximation of generalized anharmonic
      oscillators.

PMID- 9909001
TI  - Significance of an experiment of the Greenberger-Horne-Zeilinger kind.

PMID- 9909002
TI  - Collective excitations of the QED vacuum.

PMID- 9909003
TI  - Rayleigh-Schrodinger perturbation theory at large order for radial Klein-Gordon
      equations.

PMID- 9909004
TI  - One-logarithmic recoil correction in muonium hyperfine splitting.

PMID- 9909005
TI  - Corrections to the Born-Oppenheimer approximation for a harmonic oscillator.

PMID- 9909006
TI  - Lifetimes of 5d96p and 5d86s6p levels in Hg III.

PMID- 9909008
TI  - Relativistic extension of the Kay-Moses method for constructing transparent
      potentials in quantum mechanics.

PMID- 9909007
TI  - Metastable-ion lifetime studies utilizing a heavy-ion storage ring: Measurements
      on He-

PMID- 9909009
TI  - Branching ratio for the M1 decay of the 2 (2)S1/2 state in one-electron krypton.

PMID- 9909010
TI  - Precise nonvariational calculation of the two-photon annihilation rate of the
      positronium negative ion.

PMID- 9909011
TI  - Applications of coordinate-scaling procedures to the exchange-correlation energy.

PMID- 9909012
TI  - Calculation of traces of p-order replacement operators over N-electron spin
      adapted spaces.

PMID- 9909013
TI  - Hyperfine quenching of the 1s22s2p 3P0 level in berylliumlike ions.

PMID- 9909014
TI  - Pseudoconvexity of the atomic electron density: Lower and upper bounds.

PMID- 9909015
TI  - Theory of the light-force technique for measuring polarizabilities.

PMID- 9909016
TI  - Ab initio calculations of gj factors for Li, Be+, and Ba+

PMID- 9909017
TI  - Approximating q-order reduced density matrices in terms of the lower-order ones.
      I. General relations.

PMID- 9909018
TI  - Approximating q-order reduced density matrices in terms of the lower-order ones.
      II. Applications.

PMID- 9909019
TI  - Experimental analysis of H3- and D3-molecule autoionization.

PMID- 9909020
TI  - Zero-energy scattering in symmetric Coulomb systems via Faddeev approach.

PMID- 9909021
TI  - Electronic excitation of dielectronic targets by ion impact.

PMID- 9909022
TI  - Differential electronic-excitation cross sections of molecular oxygen by electron
      impact: The a 1 Delta g and 1 Sigma g states.

PMID- 9909023
TI  - Inclusion of the generalized Breit interaction in excitation of highly charged
      ions by electron impact.

PMID- 9909024
TI  - Positron-induced dissociation of organic molecules.

PMID- 9909025
TI  - Time-dependent wave-packet description of dissociative electron attachment.

PMID- 9909027
TI  - Distortion effects for electron excitation in ion-atom collisions.

PMID- 9909026
TI  - Impact-parameter dependence of the electron-electron interaction in
      (Li2+,C5+)+(H2,He) electron loss.

PMID- 9909029
TI  - Partial and differential photoionization cross sections of Cl and Br.

PMID- 9909028
TI  - H+-H- coincidences from the three-body dissociation of excited H3+

PMID- 9909030
TI  - Correlation forces in electron-scattering processes via density-functional
      theory: Electron collisions with closed-shell atoms.

PMID- 9909032
TI  - Model independence of scattering of three identical bosons in two dimensions.

PMID- 9909031
TI  - L x-ray fluorescence cross sections and intensity ratios in some high-Z elements
      excited by 23.62- and 24.68-keV photons.

PMID- 9909033
TI  - Calculation of electron-lithium scattering using the coupled-channel optical
      method.

PMID- 9909034
TI  - Transferability of local-density norm-conserving pseudopotentials to electron
      molecule-collision calculations.

PMID- 9909035
TI  - Nonperturbative stopping-power calculation for bare and neutral hydrogen incident
      on He.

PMID- 9909036
TI  - Directional characteristics of the moments of the dipole-oscillator-strength
      distribution of molecules: H2 and H2O.

PMID- 9909037
TI  - Measurement of 1s2s 3S1-1s2p 3P2,0 wavelengths in heliumlike neon.

PMID- 9909038
TI  - K-shell excitation of the water, ammonia, and methane molecules using high
      resolution photoabsorption spectroscopy.

PMID- 9909039
TI  - Hyperfine spectra of the radioactive isotopes Kr81 and Kr85.

PMID- 9909040
TI  - Temperature dependence of the pure rotational band of HD: Interference, widths,
      and shifts.

PMID- 9909041
TI  - Optical and microwave study of a very weak perturbation in high Rydberg states of
      lutetium.

PMID- 9909042
TI  - Photoabsorption of atoms inside C60.

PMID- 9909043
TI  - Stark effect for the Rydberg states of the krypton atom near the ionization
      threshold.

PMID- 9909045
TI  - Electric-field ionization of Rydberg states of H3.

PMID- 9909044
TI  - Ps formation in the laser-assisted e+-He collision.

PMID- 9909046
TI  - Quantitative investigation of the resonant nonlinear Faraday effect under
      conditions of optical hyperfine pumping.

PMID- 9909047
TI  - Stark effect in nonlinear Jaynes-Cummings models.

PMID- 9909048
TI  - Signal-pump entanglement in quantum k-photon down-conversion.

PMID- 9909050
TI  - Optical multiwave mixing: Dark solitary wave trains and quasiperiodic dynamics.

PMID- 9909049
TI  - Near-dipole-dipole effects in dense media: Generalized Maxwell-Bloch equations.

PMID- 9909051
TI  - Leading role of optical phase instabilities in the formation of certain laser
      transverse patterns.

PMID- 9909052
TI  - Role of internal degrees of freedom in laser-light coherence.

PMID- 9909053
TI  - Canonical approach to photon pressure.

PMID- 9909054
TI  - Einstein-Podolsky-Rosen state for space-time variables in a two-photon
      interference experiment.

PMID- 9909055
TI  - Theory of four-wave mixing using an amplitude approach.

PMID- 9909056
TI  - Cavity-field-assisted atomic relaxation and suppression of resonance fluorescence
      at high intensities.

PMID- 9909057
TI  - Laser-assisted nuclear gamma excitation by the inverse electronic-bridge process.

PMID- 9909058
TI  - Spectrum of light scattered by a strongly driven atom.

PMID- 9909059
TI  - Frequency shifts in spontaneous emission from two interacting atoms.

PMID- 9909060
TI  - Micromaser spectrum: Trapped states.

PMID- 9909062
TI  - Magnetic-field-induced sum-frequency mixing in sodium vapor.

PMID- 9909061
TI  - Generation of a train of three-dimensional optical solitons in a self-focusing
      medium.

PMID- 9909063
TI  - Resonance fluorescence from quantized one-dimensional molasses.

PMID- 9909064
TI  - Atomic dynamics with photon-dressed core states.

PMID- 9909065
TI  - Measurement of line overlap for resonant photopumping of transitions in neonlike
      ions by nickel-like ions.

PMID- 9909066
TI  - Collisional effects in gas lasers.

PMID- 9909067
TI  - "Scarring" and suppression of ionization in very intense radiation fields.

PMID- 9909068
TI  - Role of pumping statistics and dynamics of atomic polarization in quantum
      fluctuations of laser sources.

PMID- 9909069
TI  - Phase-matching effects in strong-field harmonic generation.

PMID- 9909071
TI  - Atomic tests of the Zeno effect.

PMID- 9909070
TI  - Relativistic calculation of multiphoton ionization in strong laser fields.

PMID- 9909072
TI  - Spatiotemporal oscillations in a semiconductor etalon.

PMID- 9909073
TI  - Alternative derivation of the Pegg-Barnett phase operator.

PMID- 9909074
TI  - P-wave shape resonances in positronium ions.

PMID- 9909076
TI  - Simple evaluation of the screened Lamb shift of heavily ionized high-Z atoms.

PMID- 9909075
TI  - Restoration of neutron interferometer contrast by post-interference filtering.

PMID- 9909078
TI  - Evolution of the 1 Sigma + radiative lifetime of copper halides.

PMID- 9909079
TI  - Variational stability and the form of the Schwinger multichannel variational
      principle.

PMID- 9909077
TI  - Construction of the exact exchange potential of density-functional theory.

PMID- 9909081
TI  - Enhancement of resonant structure in the photoelectron spectra of excited He(2
      (1)Se) above the n=2 threshold.

PMID- 9909080
TI  - Sequential ionization in 3He with a 1.5-ps 1- microm laser pulse.

PMID- 9909082
TI  - Mass effects in the theoretical determination of nuclear-spin relaxation rates
      for atomic hydrogen and deuterium.

PMID- 9909083
TI  - Ions produced from condensed CO targets under energetic ion impact.

PMID- 9909084
TI  - Electron correlation in the continuum: The e-2e process for small relative
      momenta of the outgoing electrons.

PMID- 9909085
TI  - Toward measurements of total cross sections for positrons and electrons scattered
      by potassium and rubidium atoms.

PMID- 9909086
TI  - Determination of the lifetime width of the argon L1-hole state.

PMID- 9909087
TI  - Angular-momentum coupling in spectroscopic relaxation cross sections:
      Consequences for line coupling in bending bands.

PMID- 9909088
TI  - Excited-level populations in C IV in a recombining Theta -pinch plasma.

PMID- 9909089
TI  - Lifetimes of Rydberg levels in the perturbed 6snp 3P2 series of ytterbium I.

PMID- 9909090
TI  - Eigenstates of linear combinations of phase operators.

PMID- 9909091
TI  - Effects of the dipole-dipole interaction on atomic dynamics in M-photon
      processes.

PMID- 9909092
TI  - Above-threshold ionization of atomic hydrogen via resonant intermediate states.

PMID- 9909093
TI  - Failure of an atomic-injection model for the description of pump fluctuations in
      masers and lasers.

PMID- 9909094
TI  - Dynamical stabilization of atoms in intense laser pulses accessible to
      experiment.

PMID- 9909095
TI  - Plasma dispersion in ultrashort-pulse x-ray lasers.

PMID- 9909096
TI  - Comparison of Vogel-Schleich phase theory with quantum phase measurements.

PMID- 9909097
TI  - Role of atomic coherence in lasing without inversion.

PMID- 9909098
TI  - Self-frequency shift of dark solitons in optical fibers.

PMID- 9909099
TI  - Angular dependence of positronium formation in molecular hydrogen.

PMID- 9909100
TI  - Background level and counter efficiencies required for a loophole-free Einstein
      Podolsky-Rosen experiment.

PMID- 9909101
TI  - Possibility of observing parity nonconservation by measuring the nuclear anapole
      moment using the NMR frequency shift in a laser beam.

PMID- 9909102
TI  - Measurement of autoionization rates for electron emission above a metal surface.

PMID- 9909104
TI  - Evidence for autoexcitation producing inner-shell vacancies in slow ion-atom
      collisions.

PMID- 9909103
TI  - K-shell Auger spectrum of atomic oxygen.

PMID- 9909105
TI  - Multiplet-changing Auger transitions in valence double photoionization.

PMID- 9909106
TI  - Effect of speed-changing collisions on spectral line shape.

PMID- 9909107
TI  - Density-functional study of niobium clusters.

PMID- 9909108
TI  - Classical theory of intense-field stabilization.

PMID- 9909109
TI  - Microwave-driven He Rydberg atoms: Floquet-state degeneracy lifted by a second
      frequency, Stueckelberg oscillations, and their destruction by added noise.

PMID- 9909110
TI  - Classical stabilization of the hydrogen atom in a monochromatic field.

PMID- 9909111
TI  - Nonlinear coupling instabilities and spatial chaos in an optical open-flow
      system.

PMID- 9909112
TI  - Driven harmonic oscillators in the adiabatic Magnus approximation.

PMID- 9909113
TI  - Quantum signature of a period-doubling bifurcation and scars of periodic orbits.

PMID- 9909114
TI  - Experimental consequences of Einstein-Podolsky-Rosen-Bohm-Bell gedanken
      experiment.

PMID- 9909115
TI  - Dissipative force on a sphere moving in vacuum.

PMID- 9909116
TI  - Problem of signal transmission via quantum correlations and Einstein
      incompleteness in quantum mechanics.

PMID- 9909117
TI  - Interpretation of quantum jump and diffusion processes illustrated on the Bloch
      sphere.

PMID- 9909118
TI  - Maximum-likelihood statistics of multiple quantum phase measurements.

PMID- 9909119
TI  - Rates of quantum decoherence in regular and chaotic systems.

PMID- 9909120
TI  - Using the Pauli exclusion principle to exhibit local-realism violations in
      overlapping interferometers.

PMID- 9909121
TI  - Supersymmetry aspects of the Dirac equation in one dimension with a Lorentz
      scalar potential.

PMID- 9909123
TI  - Perturbative calculation of transition amplitudes for cesium.

PMID- 9909122
TI  - Electron-correlation and relativistic contributions to atomic dipole
      polarizabilities: Alkali-metal atoms.

PMID- 9909124
TI  - Relativistic many-body perturbation-theory calculations based on Dirac-Fock-Breit
      wave functions.

PMID- 9909125
TI  - Ionization potential for ground states of berylliumlike systems.

PMID- 9909126
TI  - Modes of angular motion in intrashell 2S+1So states of four-valence-electron
      atomic systems.

PMID- 9909128
TI  - Extremum principles for relativistic atomic structure and scattering: Two
      electron ions.

PMID- 9909127
TI  - General method to evaluate two-body integrals for relativistic atomic
      calculations.

PMID- 9909129
TI  - 7sng autoionizing states of barium.

PMID- 9909130
TI  - Ring currents in topologically complex molecules: Application to C60, C70, and
      their hexa-anions.

PMID- 9909131
TI  - Calculations of the screened self-energy and vacuum polarization in Li-like, Na
      like, and Cu-like ions.

PMID- 9909132
TI  - Nonlocal exchange- and kinetic-energy density functionals for electronic systems:
      Application to atoms and ions.

PMID- 9909133
TI  - Self-consistent local-density approximation with model Coulomb pair-correlation
      functions for electronic systems.

PMID- 9909135
TI  - Symmetry-resolved C and O K-shell photoabsorption spectra of free CO molecules.

PMID- 9909134
TI  - Lamb-shift calculations for non-Coulomb potentials.

PMID- 9909136
TI  - Target dressing effects in laser-assisted x-ray photoionization.

PMID- 9909137
TI  - Photoelectron-angular-distribution parameters for rare-gas subshells.

PMID- 9909138
TI  - Efficient variable time-stepping scheme for intense field-atom interactions.

PMID- 9909139
TI  - Energy distribution of secondary electrons in electron-impact ionization of
      hydrogenic and heliumlike ions.

PMID- 9909141
TI  - Indirect contributions to electron-impact ionization of Kr24+, Kr25+, and Xe43+

PMID- 9909140
TI  - Doubly differential electron-production cross sections for 200-1500-eV e-+H2
      collisions.

PMID- 9909142
TI  - Multichannel photoionization of metastable He(2 (3)Se): A complete study of the
      3Po resonances between the N=2 and 3 thresholds.

PMID- 9909143
TI  - Theory of laser-induced associative ionization of ultracold Na.

PMID- 9909144
TI  - Collisional ionization and destruction cross sections for hydrogen and helium
      Rydberg atoms on Ar, Xe, and N2: Failure of the independent-particle model.

PMID- 9909146
TI  - Semiclassical treatment of two-center electron-electron interactions in energetic
      atomic collisions: Screening effects.

PMID- 9909145
TI  - Electron-impact excitation of the Rb 7 (2)S1/2, 8 (2)S1/2, 5 (2)D3/2, and 6
      (2)D3/2 states.

PMID- 9909147
TI  - Dependence of electron-impact excitation cross sections on the initial
      vibrational quantum number in H2 and D2 molecules: X 1 Sigma g+-->B 1 Sigma u+
      and 1 Sigma g+-->C 1 Pi u transitions.

PMID- 9909148
TI  - s-wave photodetachment in a static electric field.

PMID- 9909149
TI  - Multielectron inner-shell photoexcitation in absorption spectra of Kr: Theory and
      experiment.

PMID- 9909150
TI  - 3 Sigma u+ bound and continuum states in e--He2+ scattering.

PMID- 9909152
TI  - Multiconfiguration multichannel Schwinger study of the C(1s) photoionization of
      CO including shake-up satellites.

PMID- 9909151
TI  - Photoionization of the 5d6p 3D1 state of barium.

PMID- 9909153
TI  - Asymptotic solution of the Schrodinger equation for three charged particles.

PMID- 9909154
TI  - Modulated barrier approach to the interaction time in tunneling for arbitrary
      potentials.

PMID- 9909155
TI  - Excitation of alkali-metal-like ions by electron impact.

PMID- 9909156
TI  - Dielectronic recombination of heliumlike ions.

PMID- 9909157
TI  - Energy loss of 0.7-MeV He ions due to the dynamic response of surface electrons.

PMID- 9909158
TI  - Double-electron excitation channels at the Br K edge of HBr and Br2.

PMID- 9909160
TI  - Ab initio study of neutral and ionized microclusters of MgO.

PMID- 9909159
TI  - Mean-field approach to the algebraic treatment of molecules: Bent molecules.

PMID- 9909161
TI  - Nonlinear optical susceptibilities of disordered aggregates: A comparison of
      schemes to account for intermolecular interactions.

PMID- 9909162
TI  - Influence of polarization effects and magnetic fields on time-resolved laser
      induced fluorescence measurements.

PMID- 9909164
TI  - Evolution of atomic motion in an intense standing wave.

PMID- 9909163
TI  - Cooling of a trapped ion in the strong-sideband regime.

PMID- 9909165
TI  - High-brightness, high-purity spin-polarized cesium beam.

PMID- 9909166
TI  - Generalized Volkov wave functions: Application to laser-assisted scattering.

PMID- 9909167
TI  - Effects of nonuniform reflective boundaries and line competition on radiation
      trapping.

PMID- 9909169
TI  - Coherence with incoherent light: A new type of quantum beat for a single atom.

PMID- 9909168
TI  - Reflection and diffraction of atomic de Broglie waves by an evanescent laser
      wave.

PMID- 9909170
TI  - Laser cooling of trapped ions in a squeezed vacuum.

PMID- 9909171
TI  - Theory of amplification of nonlinear guided waves.

PMID- 9909172
TI  - Stability analysis for an optical bistable dye system.

PMID- 9909174
TI  - Jaynes-Cummings model with quasiclassical fields: The effect of dissipation.

PMID- 9909173
TI  - Amplification and the wave-particle duality.

PMID- 9909176
TI  - Period-doubling route to chaos in a semiconductor laser with weak optical
      feedback.

PMID- 9909175
TI  - Long-distance evolution in transient stimulated Raman scattering.

PMID- 9909177
TI  - Fluorescence in Mg IX emission at 48.340 A from Mg pinch plasmas photopumped by
      Al XromanI line radiation at 48.338.

PMID- 9909178
TI  - Frequency shift in an oscillator with photorefractive gain.

PMID- 9909179
TI  - Squeezing in nondegenerate two-photon processes in a cavity quantum
      electrodynamics of a three-level and a two-level Rydberg atom.

PMID- 9909181
TI  - Atomic population inversion and enhancement of resonance fluorescence in a
      cavity.

PMID- 9909180
TI  - Resonant-second-harmonic generation of laser radiation in a semiconductor.

PMID- 9909182
TI  - Control of visibility in the interference of signal photons by delays imposed on
      the idler photons.

PMID- 9909183
TI  - Interference between nearly resonant three-photon excitation and third-harmonic
      generation probed by the cancellation of four-photon resonances.

PMID- 9909184
TI  - Molecular reorientation during dissociative multiphoton ionization.

PMID- 9909186
TI  - Macroscopic and submacroscopic fields in micromasers with non-Poissonian pumping.

PMID- 9909185
TI  - Ionization suppression in a very-short-range potential.

PMID- 9909187
TI  - Second-harmonic generation inside a laser cavity with slowly decaying atoms.

PMID- 9909189
TI  - Shannon entropy and the eigenstates of the single-mode squeeze operator.

PMID- 9909188
TI  - Giant-laser-pulse-induced Rabi sideband of a multilevel dressed atom.

PMID- 9909190
TI  - Hopf sideband bifurcation and chaos in fiber lasers with injected signal.

PMID- 9909191
TI  - Quantum noise in Raman lasers: Effects of pump bandwidth and super- and sub
      Poissonian pumping.

PMID- 9909192
TI  - Fabry-Perot interferometer for atoms.

PMID- 9909193
TI  - Relativistic electron- and proton-impact ionization of highly stripped heavy ions
      determined from projectile-electron loss in H2 and He.

PMID- 9909195
TI  - Relation between ideal and feasible phase concepts.

PMID- 9909194
TI  - Strongly perturbed quantum systems.

PMID- 9909197
TI  - Exact exchange functional for the hydrogen atom.

PMID- 9909196
TI  - Unitary operator for an arbitrary number of coupled identical oscillators.

PMID- 9909198
TI  - Second-order Born cross sections for positronium formation in positron-hydrogen
      collisions.

PMID- 9909199
TI  - Angular distributions for near-threshold (e,2e) processes for Li and Mg.

PMID- 9909200
TI  - Departure from velocity proportionality in low-energy electronic stopping.

PMID- 9909201
TI  - Atomic Compton-scattering cross sections for small momentum transfer.

PMID- 9909202
TI  - Effect of exchange on the binary-encounter-electron double-differential cross
      section in Cq+-H2 collisions at 0.75 MeV/amu.

PMID- 9909203
TI  - Photodetachment of H- in the presence of a strong laser field: Effects of the
      laser spatial inhomogeneity.

PMID- 9909204
TI  - Steady-state analysis of a single-mode laser with correlations between additive
      and multiplicative noise.

PMID- 9909205
TI  - Relationship between the overall permutation and time-reversal symmetries in the
      nonlinear optical hyperpolarizabilities.

PMID- 9909206
TI  - Comment on "Intrinsic decoherence in quantum mechanics"

PMID- 9909208
TI  - Construction of exact Kohn-Sham orbitals from a given electron density.

PMID- 9909207
TI  - Reply to "Comment on 'Intrinsic decoherence in quantum mechanics' "

PMID- 9909209
TI  - Electron capture in Ar+-ion collisions with laser-aligned Rydberg atoms.

PMID- 9909210
TI  - Dielectronic recombination cross sections of fluorinelike xenon.

PMID- 9909211
TI  - Collective spin excitations of alkali-metal clusters.

PMID- 9909212
TI  - Single and double ionization and strong-field stabilization of a two-electron
      system.

PMID- 9909213
TI  - Stabilization of unstable stationary states in optical bistability.

PMID- 9909214
TI  - Circular Rydberg orbits in circularly polarized microwave radiation.

PMID- 9909216
TI  - Quantum dynamics near a classical separatrix.

PMID- 9909215
TI  - Restless optical vortex.

PMID- 9909217
TI  - Classical motion of meter variables in the quantum theory of measurement.

PMID- 9909218
TI  - Scheme for measuring a Berry phase in an atom interferometer.

PMID- 9909219
TI  - Semiclassical expansion for systems with internal degrees of freedom.

PMID- 9909220
TI  - Random perturbation of systematic degeneracies and quantum chaos.

PMID- 9909221
TI  - Quantum electrodynamics with nonrelativistic sources. V. Electromagnetic field
      correlations and intermolecular interactions between molecules in either ground
      or excited states.

PMID- 9909222
TI  - Wigner-Kirkwood expansion for cross sections.

PMID- 9909223
TI  - Anharmonic and nonclassical effects of the quantum-deformed harmonic oscillator.

PMID- 9909224
TI  - Exact space-time propagator for the step potential.

PMID- 9909226
TI  - Measurement of time-dependent quantum phases.

PMID- 9909225
TI  - Generalized covariance condition and quantization in curved configuration space.

PMID- 9909227
TI  - Quantum-to-classical limit of a dynamically driven spin.

PMID- 9909228
TI  - Densities of degeneracies and near-degeneracies.

PMID- 9909230
TI  - Polarizabilities and susceptibilities from high-angular-momentum Rydberg states
      of halogen and inert-gas isoelectronic sequences.

PMID- 9909229
TI  - Excitation of spin flips in geonium at small cyclotron quantum numbers:
      Transition rates and frequency shifts.

PMID- 9909231
TI  - Nonmonotonicity of the atomic electron momentum density.

PMID- 9909233
TI  - Intermittent chaos in Hamiltonian systems: The three-dimensional hydrogen atom in
      magnetic fields.

PMID- 9909232
TI  - Doubly excited 1,3Pe states in heliumlike systems.

PMID- 9909235
TI  - Group-theoretical and topological analysis of localized rotation-vibration
      states.

PMID- 9909234
TI  - Calculation of the two-photon-annihilation contribution to the positronium
      hyperfine interval at order m alpha 6.

PMID- 9909237
TI  - Density-functional-theory softness kernel.

PMID- 9909236
TI  - Finite-element multiconfiguration Hartree-Fock calculations of the atomic
      quadrupole moments of excited states of Be, Al, In, Ne, Ar, Kr, and Xe.

PMID- 9909238
TI  - Electron correlation in doubly excited states of the hydrogen molecule.

PMID- 9909240
TI  - Calculation of the hyperfine fields in the noble-metal atoms.

PMID- 9909239
TI  - Correlation energies of Be-like atoms: A multimodel space many-body perturbation
      calculation with finite basis sets.

PMID- 9909241
TI  - Hierarchy of equations for the energy functional of the density-functional
      theory.

PMID- 9909242
TI  - Supersymmetry and tunneling in an asymmetric double well.

PMID- 9909243
TI  - Numerical study of the quasi-Landau resonances of sodium.

PMID- 9909244
TI  - Resonant excitation of relativistic-ion cyclotron orbital motion.

PMID- 9909245
TI  - Application of Hilbert-space coupled-cluster theory to simple (H2)2 model
      systems: Planar models.

PMID- 9909246
TI  - Symmetry in density-functional theory.

PMID- 9909247
TI  - Accurate optimized-potential-model solutions for spherical spin-polarized atoms:
      Evidence for limitations of the exchange-only local spin-density and generalized
      gradient approximations.

PMID- 9909248
TI  - Semianalytic theory of Rydberg electron diamagnetism. II.

PMID- 9909250
TI  - Multiple-electron removal and molecular fragmentation of CO by fast F4+ impact.

PMID- 9909249
TI  - Two-photon coincident emission from thick targets for 70-keV incident electrons.

PMID- 9909252
TI  - Closed expressions for partial-wave photoelectron spectra and angular
      distributions: A ground-state hydrogen atom struck by a temporal delta -function
      pulse.

PMID- 9909251
TI  - Path-integral approach to resonant electron-molecule scattering.

PMID- 9909253
TI  - Ab initio calculation of frequency-dependent atomic dipole polarizability.

PMID- 9909254
TI  - Low-energy total and differential cross sections for the electron-impact
      excitation of Si2+ and Ar6+

PMID- 9909255
TI  - Photoelectron angular distributions for two-photon ionization of atomic rubidium.

PMID- 9909256
TI  - Electron-impact ionization of Si6+ and Si7+ ions.

PMID- 9909257
TI  - Analysis of the first Feshbach resonances in electron collisions in rare gases.

PMID- 9909258
TI  - Multichannel quantum-defect approach for two-photon processes.

PMID- 9909260
TI  - Angular distribution of electrons elastically scattered from ozone.

PMID- 9909259
TI  - Stopping powers of the noble gases for (0.3-10)-MeV nitrogen ions.

PMID- 9909261
TI  - Doubly differential cross section for the ionization of the hydrogen molecule by
      the impact of 100-eV electrons.

PMID- 9909263
TI  - Resonance contributions to the electron-impact ionization of few-electron highly
      charged ions.

PMID- 9909262
TI  - Satellite structure of the xenon valence shell by electron-momentum spectroscopy.

PMID- 9909264
TI  - Multitrajectory semiclassical method for the treatment of nonadiabatic atom
      molecule collisions.

PMID- 9909266
TI  - Saddle-point shifts in ionizing collisions.

PMID- 9909265
TI  - Ionization and excitation of 4p45p levels of Kr II by electron impact.

PMID- 9909267
TI  - Quasimolecular x-ray spectrum from 117-keV Ne9++Ne collisions.

PMID- 9909268
TI  - 15-state R-matrix investigation of resonances in elastic scattering of electrons
      from atomic hydrogen at low energies.

PMID- 9909269
TI  - Electron-hydrogen-atom ionization collisions at intermediate (5I0-20I0) and high
      ( >~ 20I0) energies.

PMID- 9909271
TI  - Subshell-dependent relaxation in the Auger effect.

PMID- 9909270
TI  - Partial cross sections for single- and double-electron capture by multiply
      charged ions colliding with He.

PMID- 9909272
TI  - Spin-resolved elastic scattering of electrons from sodium.

PMID- 9909274
TI  - Population of the 3P2,1,0 fine-structure states in the 3s and 3p photoionization
      of atomic chlorine.

PMID- 9909273
TI  - Angle-resolved photoelectron spectrometry of atomic nitrogen.

PMID- 9909275
TI  - Photodetachment cross section of H- in crossed electric and magnetic fields. I.
      Closed-orbit theory.

PMID- 9909276
TI  - Photodetachment cross section of H- in crossed electric and magnetic fields. II.
      Quantum formulas and their reduction to the result of the closed-orbit theory.

PMID- 9909277
TI  - Quantitative analysis in low-energy-electron transmission and reflection
      spectroscopy.

PMID- 9909278
TI  - Stopping power of an electron gas for antiprotons at intermediate velocities.

PMID- 9909279
TI  - Distorted-wave calculation of stopping powers for light ions traversing H
      targets.

PMID- 9909280
TI  - Molecular-orbital theory for the stopping power of atoms in the low-velocity
      regime: The case of helium in alkali metals.

PMID- 9909281
TI  - K beta spectra of heliumlike iron from tokomak-fusion-test-reactor plasmas.

PMID- 9909282
TI  - Wavelengths and isotope shifts for lines of astrophysical interest in the
      spectrum of doubly ionized mercury (Hg III).

PMID- 9909283
TI  - Vibrationally resolved carbon core excitations in alkane molecules.

PMID- 9909284
TI  - Analysis of the third spectrum of iodine: I III.

PMID- 9909285
TI  - Noble-gas broadening rates for the 6s2 1S0-->6s6p 1,3P1 resonance and
      intercombination lines of barium.

PMID- 9909287
TI  - Asymmetric-top description of Rydberg-electron dynamics in crossed external
      fields.

PMID- 9909286
TI  - Resonances in electron scattering on zero-range potential in a magnetic field.

PMID- 9909288
TI  - Transverse laser cooling of a metastable argon beam: Dependence on the
      interaction time.

PMID- 9909289
TI  - Theory and computation of electric-field-induced tunneling rates of
      polyelectronic atomic states.

PMID- 9909290
TI  - Collisional redistribution in Hg-Kr: Polarization spectrum of the redistributed
      light.

PMID- 9909292
TI  - Hydrogenic circular states in a superstrong magnetic field: A B-spline approach.

PMID- 9909291
TI  - Atomic analogs of local and normal modes: The hydrogen atom in a generalized van
      der Waals potential.

PMID- 9909293
TI  - Transformations of the nonclassical states by an optical amplifier.

PMID- 9909294
TI  - Influence of the virtual-photon processes on the squeezing of light in the two
      photon Jaynes-Cummings model.

PMID- 9909295
TI  - Quantum limits in interferometric detection of gravitational radiation.

PMID- 9909297
TI  - Dynamics of a two-channel Raman-coupled cavity-QED model.

PMID- 9909296
TI  - Analytic method for solving the modified nonlinear Schrodinger equation
      describing soliton propagation along optical fibers.

PMID- 9909298
TI  - Experimental study of absorption and gain by two-level atoms in a time-delayed
      non-Markovian optical field.

PMID- 9909299
TI  - Suppression of forward-propagating stimulated hyper-Raman emission in cesium
      vapor due to four-wave-mixing interference.

PMID- 9909300
TI  - First-order exact solutions of the nonlinear Schrodinger equation in the normal
      dispersion regime.

PMID- 9909301
TI  - Limitations of pump-probe femtosecond time-resolved experiments: Time-dependent
      absorption and dispersion line shapes.

PMID- 9909302
TI  - Electron scattering by a potential in the presence of a strong single-mode
      radiation field.

PMID- 9909303
TI  - Phase properties and entanglement of the field modes in a two-mode coupler with
      intensity-dependent coupling.

PMID- 9909305
TI  - Interaction of radiation with matter: Integrable problems.

PMID- 9909304
TI  - Second-harmonic generation and photon bunching in multimode laser beams.

PMID- 9909307
TI  - Perfect correlations of three-particle entangled states in cavity QED.

PMID- 9909306
TI  - Stabilization and characterization of unstable steady states in a laser.

PMID- 9909308
TI  - Two-parameter family of exact solutions of the nonlinear Schrodinger equation
      describing optical-soliton propagation.

PMID- 9909309
TI  - Nonlocal effects in propagation through absorbing media.

PMID- 9909310
TI  - Properties of an electron in a quantum double well driven by a strong laser:
      Localization, low-frequency, and even-harmonic generation.

PMID- 9909311
TI  - Quantum optical master equations: The use of damping bases.

PMID- 9909312
TI  - Two-photon bound states: The diphoton bullet in dispersive self-focusing media.

PMID- 9909313
TI  - Wigner distribution functions on a linear amplifier.

PMID- 9909314
TI  - Quantum optics of traveling-wave attenuators and amplifiers.

PMID- 9909315
TI  - Dipole interactions in a resonant quantum coherent gas.

PMID- 9909317
TI  - Theory of self-induced transparency in a Kerr host medium beyond the slowly
      varying-envelope approximation.

PMID- 9909316
TI  - "Squeezed states" in Helmholtz optics.

PMID- 9909319
TI  - Cooling of atoms in colored vacua.

PMID- 9909318
TI  - Dynamics of the spontaneous emission of an atom into the photon-density-of-states
      gap: Solvable quantum-electrodynamical model.

PMID- 9909320
TI  - Detection of a weak external signal via the switch-on-time statistics of a
      semiconductor laser.

PMID- 9909321
TI  - Homodyne photon statistics of the subthreshold degenerate parametric oscillator.

PMID- 9909322
TI  - Energy dependence of the density of the generalized oscillator strength of atomic
      hydrogen.

PMID- 9909324
TI  - Approximate topology and the nonexistence of spin-symmetry species of hindered
      methyl groups.

PMID- 9909323
TI  - Boundary conditions across a delta -function potential in the one-dimensional
      Dirac equation.

PMID- 9909325
TI  - Topological phase due to electric dipole moment and magnetic monopole
      interaction.

PMID- 9909326
TI  - Quantum state structure of a hydrogen atom in a magnetic field.

PMID- 9909327
TI  - Accurate ground-state calculations of H2+ using basis sets of atom-centered
      Slater-type orbitals.

PMID- 9909329
TI  - Energy spectrum of anyons in a magnetic field.

PMID- 9909328
TI  - Deuterium atomic mass from Fourier-transform-ion-cyclotron-resonance measurement
      of the mass difference between 1H2O+ and 2HO+

PMID- 9909330
TI  - He photoionization to the doubly excited (2pnd) and (sp,2n-) 1Po series.

PMID- 9909331
TI  - Bound-electron-positron pair production in relativistic heavy-ion collisions.

PMID- 9909333
TI  - Comment on "Gravity as a zero-point-fluctuation force"

PMID- 9909332
TI  - Unification of Jaynes-Cummings models.

PMID- 9909334
TI  - Reply to "Comment on 'Gravity as a zero-point-fluctuation force' "

PMID- 9909335
TI  - Erratum: Dynamical spatial-pattern memory in globally coupled lasers

PMID- 9909336
TI  - Erratum: Atomic K-shell binding energies of multiply charged neon ions studied by
      zero-degree Auger-electron spectroscopy

PMID- 9909338
TI  - Noise in Mermin's n-particle Bell inequality.

PMID- 9909337
TI  - Electron-tunneling spectroscopy: A test of quantum mechanics.

PMID- 9909339
TI  - Phase-space anomalies and canonical transformations.

PMID- 9909340
TI  - Conditionally exactly soluble class of quantum potentials.

PMID- 9909341
TI  - Residual-ion orientation after autoionization.

PMID- 9909342
TI  - Chaotic scattering of electrons with He+

PMID- 9909344
TI  - Comparative analysis of the threshold behavior of two-electron escape in electron
      impact ionization of valence-1 atoms.

PMID- 9909343
TI  - Isotope-selective photoionization spectroscopy of barium.

PMID- 9909345
TI  - Hyperfine quenching and measurement of the 2 (3)P0-2 (3)P1 fine-structure
      splitting in heliumlike silver (Ag45+).

PMID- 9909347
TI  - Phase measurement and Q function.

PMID- 9909346
TI  - Double photoionization of molecular hydrogen.

PMID- 9909348
TI  - Chaotic and cooperative regimes for the micromaser.

PMID- 9909349
TI  - Ionization of highly excited hydrogen atoms by a circularly polarized microwave
      field.

PMID- 9909350
TI  - High-visibility interference in a Bell-inequality experiment for energy and time.

PMID- 9909351
TI  - Measurements of light-scattering noise accompanying two-wave mixing in a Kerr
      medium.

PMID- 9909353
TI  - Quantum features in the scattering of atoms from an optical standing wave.

PMID- 9909352
TI  - High-order harmonic generation by ultrashort KrF and Ti:sapphire lasers.

PMID- 9909355
TI  - Experimental characterization of unstable periodic orbits by controlling chaos.

PMID- 9909354
TI  - Lasing threshold behavior of microcavities: Observation by polarization and
      spectroscopic measurements.

PMID- 9909356
TI  - Diagonalization of multicomponent wave equations with a Born-Oppenheimer example.

PMID- 9909357
TI  - Quantum interference effects for nonseparable two-electron systems.

PMID- 9909358
TI  - Reconstruction of spectra in the discrete quantum mechanics: Elements of lattice
      quantum engineering.

PMID- 9909359
TI  - Duality, measurements, and factorization in finite quantum systems.

PMID- 9909360
TI  - WKB wave functions without matching.

PMID- 9909361
TI  - Nonlinear Schrodinger equation and wave-function collapse: An unreliable
      consequence of the semiclassical approximation.

PMID- 9909362
TI  - Level dynamics: An approach to the study of avoided level crossings and
      transition to chaos.

PMID- 9909363
TI  - Quantum projection noise: Population fluctuations in two-level systems.

PMID- 9909364
TI  - Universal and nonuniversal statistical properties of levels and intensities for
      chaotic Rydberg molecules.

PMID- 9909365
TI  - Ermakov-Lewis invariant from the Wigner function of a squeezed coherent state.

PMID- 9909366
TI  - Path-generating function of the diamagnetic Kepler problem.

PMID- 9909368
TI  - Accelerated clock principles in special relativity.

PMID- 9909367
TI  - Aharonov-Bohm scattering of wave packets by Maxwell coils.

PMID- 9909370
TI  - Consistent propagator theory based on the extended coupled-cluster
      parametrization of the ground state.

PMID- 9909369
TI  - Accurate computation of eigenfunctions for Schrodinger operators associated with
      Coulomb-type potentials.

PMID- 9909371
TI  - Ground-state correlation energies for atomic ions with 3 to 18 electrons.

PMID- 9909372
TI  - Nonadiabatic variational calculations on dipositronium using explicitly
      correlated Gaussian basis functions.

PMID- 9909373
TI  - Electron-nucleus interactions in few-electron Fe ions.

PMID- 9909374
TI  - Relativistic configuration-interaction calculations of n=2 triplet states of
      heliumlike ions.

PMID- 9909375
TI  - Evaluating dynamic multipole polarizabilities and van der Waals dispersion
      coefficients of two-electron systems with a quantum Monte Carlo calculation: A
      comparison with some ab initio calculations.

PMID- 9909376
TI  - Autoionization studies of the 1s2s2p 4P5/2 levels in He-, Li I, and Be II.

PMID- 9909377
TI  - Evolution from the coplanar to the perpendicular plane geometry of helium (e,2e)
      differential cross sections symmetric in scattering angle and energy.

PMID- 9909379
TI  - K-K-electron transfer and K-shell-vacancy production cross sections for Ti
      bombarded by 28Si and 32S beams at 1.25-4.70 MeV/amu.

PMID- 9909378
TI  - Relativistic-intermediate-coupling calculations of angular distributions in
      resonant Auger decay.

PMID- 9909380
TI  - Fragmentation of CH4 caused by fast-proton impact.

PMID- 9909382
TI  - Matrix continuum distorted-wave approximation for electron capture.

PMID- 9909381
TI  - Absolute total and one- and two-electron transfer cross sections for Arq+ (8 <= q
      <= 16) on He and H2 at 2.3q keV.

PMID- 9909384
TI  - Theoretical study of the optimal conditions for the measurement of the
      differential cross section of the double ionization of helium by fast electrons.

PMID- 9909383
TI  - Investigation of spin-orbit effects in the excitation of noble gases by spin
      polarized electrons.

PMID- 9909385
TI  - Electron detachment and charge transfer for collisions of O- and S- with H.

PMID- 9909386
TI  - Resonant transfer and excitation in C3++Li collisions.

PMID- 9909388
TI  - Multiconfiguration linear-response approaches to the calculation of absolute
      photoionization cross sections: HF, H2O, and Ne.

PMID- 9909387
TI  - Experimental transition probabilities of intercombination transitions in Mg-like
      and Al-like ions of bromine.

PMID- 9909389
TI  - Intermediate ionization continua for double charge exchange at high impact
      energies.

PMID- 9909391
TI  - Regularization of Coulomb potentials in the treatment of nonresonant transitions
      to an ionizing continuum.

PMID- 9909390
TI  - Azimuthal angular dependence of recoil-ion and electron emission in 0.5-MeV p +
      He collisions.

PMID- 9909392
TI  - Repulsive wall of the He2 interaction as inferred from differential cross
      sections.

PMID- 9909393
TI  - Electron-impact ionization of the oxygen atom.

PMID- 9909394
TI  - Coincident detection of electrons ejected at large angles and target recoil ions
      produced in multiply ionizing collisions for the 1-MeV/u Oq++Ar collision system.

PMID- 9909395
TI  - Measurements of absolute Ar 3s photoionization cross sections.

PMID- 9909396
TI  - Excitation, ionization, and electron-capture processes in slow He2++H and H++He+
      collisions.

PMID- 9909397
TI  - Angular-momentum distributions following impact of slow ions on Na(nd) Rydberg
      atoms.

PMID- 9909398
TI  - Angular distribution of dissociated deuterons by impact of 2-16-MeV O8+

PMID- 9909400
TI  - Impact-parameter formulation for electron capture from molecular targets.

PMID- 9909399
TI  - Molecular treatment of electron capture at low to intermediate collision
      energies: Collisions of B4+ ions with H atoms.

PMID- 9909401
TI  - Doubly differential secondary-electron yields following 8-MeV/u U68+- and 3.5
      MeV/u U38+-ion impact on a thin carbon-foil target.

PMID- 9909402
TI  - Calculation of electron-potassium scattering.

PMID- 9909403
TI  - Channel interaction and relaxation effects in Xe N4,5OO Auger transitions.

PMID- 9909405
TI  - Schwinger multichannel method for positron-molecule scattering.

PMID- 9909404
TI  - Molecular-alignment dependence in the transfer excitation of H2.

PMID- 9909406
TI  - Xe L and M x-ray emission following Xe44-48+ ion impact on Cu surfaces.

PMID- 9909407
TI  - Emission of low-energy electrons from multicharged ions interacting with metal
      surfaces.

PMID- 9909408
TI  - Channeling radiation beyond the continuum model: The phonon "Lamb shift" and
      higher-order corrections.

PMID- 9909409
TI  - K-shell photoabsorption spectrum of C II.

PMID- 9909411
TI  - Anharmonic-potential-effective-charge approach for computing Raman cross sections
      of a gas.

PMID- 9909410
TI  - H2, D2, and HD ionization potentials by accurate calibration of several iodine
      lines.

PMID- 9909412
TI  - Spin-dependent rotational autoionization of H2 Rydberg states.

PMID- 9909413
TI  - Collision-induced first overtone band of gaseous hydrogen from first principles.

PMID- 9909414
TI  - Multielectron transition effects on x-ray-fluorescence spectra.

PMID- 9909416
TI  - Numerical study of the one-dimensional hydrogen atom in an external time
      dependent electric field.

PMID- 9909415
TI  - Variational and diffusion Monte Carlo techniques for quantum clusters.

PMID- 9909417
TI  - Threshold and resonance phenomena in ultracold ground-state collisions.

PMID- 9909418
TI  - Femtosecond transition-state experiments and a unique dissociation time.

PMID- 9909420
TI  - Quadratic Zeeman effect in hydrogen Rydberg states: Rigorous bound-state error
      estimates in the weak-field regime.

PMID- 9909419
TI  - Recoil-induced resonances in pump-probe spectroscopy including effects of level
      degeneracy.

PMID- 9909421
TI  - Stark effect and rotational-series interactions on high Rydberg states of
      molecular hydrogen.

PMID- 9909422
TI  - Laser cooling at low intensity in a strong magnetic field.

PMID- 9909423
TI  - Statistical properties of pulses: Application to modulated gas lasers.

PMID- 9909424
TI  - High-pump-power effects on resonant nearly degenerate four-wave-mixing signal for
      homogeneously and inhomogeneously broadened two-level systems.

PMID- 9909425
TI  - Closed-form solutions for the production of ions in the collisionless ionization
      of gases by intense lasers.

PMID- 9909427
TI  - Effects of the dipole-dipole interaction on dynamic properties and atomic
      coherent trapping of a two-atom system.

PMID- 9909426
TI  - Spectrum of quantum electromagnetic fluctuations in rectangular cavities.

PMID- 9909428
TI  - High-sensitivity study of laser-induced birefringence and dichroism in the
      ionization continuum of cesium.

PMID- 9909429
TI  - Statistics of difference events in homodyne detection.

PMID- 9909431
TI  - Exact solution of a two-channel cavity QED model using coupled angular momenta.

PMID- 9909430
TI  - Fluctuations and correlations in quantum-optical systems: An alternative
      computational approach.

PMID- 9909432
TI  - Revivals made simple: Poisson summation formula as a key to the revivals in the
      Jaynes-Cummings model.

PMID- 9909434
TI  - Transverse effects in coherently driven nonlinear cavities.

PMID- 9909433
TI  - Hyper-Raman scattering and three-photon resonant ionization: Competitive effects.

PMID- 9909436
TI  - Correlated amplification of light.

PMID- 9909435
TI  - Coherence and phase dynamics of spatially coupled solid-state lasers.

PMID- 9909437
TI  - Amplification of superposition states in phase-sensitive amplifiers.

PMID- 9909439
TI  - Phase quasi-integral for stimulated Raman scattering initiated by quantum
      fluctuations and statistics of solitonlike random pulses in a depleted pump.

PMID- 9909438
TI  - Growth from spontaneous emission in a Raman multipass cell.

PMID- 9909441
TI  - Perturbations of optical solitons.

PMID- 9909440
TI  - Effect of laser intensity fluctuations on laser linewidth.

PMID- 9909442
TI  - Collisional frequency shifts and line broadening in the cryogenic deuterium
      maser.

PMID- 9909443
TI  - Optimization of single-stage x-ray laser coherence.

PMID- 9909444
TI  - Field-theoretical derivation of the master equation in quantum optics.

PMID- 9909445
TI  - Amplitude-squared squeezing in the multiphoton Jaynes-Cummings model: Effects of
      the atomic coherent states and detuning.

PMID- 9909446
TI  - Regenerative spiking oscillation in a semiconductor laser with a nonlinear
      delayed feedback.

PMID- 9909447
TI  - Source-correlation effects in the time domain.

PMID- 9909448
TI  - Entropy and attractor dimension as measures of the field-atom interaction.

PMID- 9909450
TI  - Quantum phenomena in nonstationary media.

PMID- 9909449
TI  - Violation of Bell's inequality by macroscopic states generated via parametric
      down-conversion.

PMID- 9909451
TI  - Velocity-changing-collision effects in self-pulsing lasers.

PMID- 9909452
TI  - Excitation of a single trapped electron by phase-sensitive back-action.

PMID- 9909453
TI  - Influence of external potentials on optical Ramsey fringes in atomic
      interferometry.

PMID- 9909455
TI  - Three-dimensional relativistic model of a bound particle in an intense laser
      field.

PMID- 9909454
TI  - Spontaneous-emission coupling factor and mode characteristics of planar
      dielectric microcavity lasers.

PMID- 9909456
TI  - Squeezed states with thermal noise. I. Photon-number statistics.

PMID- 9909457
TI  - Squeezed states with thermal noise. II. Damping and photon counting.

PMID- 9909459
TI  - Nonlocal theory of accelerated observers.

PMID- 9909458
TI  - Photoionization of the excited Cs 5d state.

PMID- 9909460
TI  - Analytic functions for atomic momentum-density distributions and Compton profiles
      of K and L shells.

PMID- 9909461
TI  - Variational approach for approximating energy levels.

PMID- 9909462
TI  - Roothaan-Hartree-Fock wave functions for atoms with Z <= 54.

PMID- 9909463
TI  - Dispersion interactions between excited atoms.

PMID- 9909465
TI  - Inverse operators in Fock space studied via a coherent-state approach.

PMID- 9909464
TI  - Antiproton stopping power in hydrogen below 120 keV and the Barkas effect.

PMID- 9909467
TI  - Effects of damping on the quantum limits to optical phase shifts in Kerr
      nonlinear media.

PMID- 9909466
TI  - Guide to fabricating bistable-soliton-supporting media.

PMID- 9909468
TI  - Comment on "Operational approach to the phase of a quantum field"

PMID- 9909470
TI  - Phase measurements.

PMID- 9909469
TI  - Reply to "Comment on 'Operational approach to the phase of a quantum field' "

PMID- 9909471
TI  - Reply to "Phase measurements"

PMID- 9909472
TI  - Coordinate and momentum representations of the q-deformed oscillator and their
      interpretation.

PMID- 9909473
TI  - [h-bar] expansion for the periodic-orbit quantization of hyperbolic systems.

PMID- 9909475
TI  - Low-energy scattering in the p+p micro system via the Faddeev approach: Virtual
      state effects.

PMID- 9909474
TI  - Measurement of dielectronic recombination in He+ ions.

PMID- 9909476
TI  - Cross section for coincident two-photon emission at +/-90 degrees in electron
      atom collisions.

PMID- 9909478
TI  - Double ionization of helium by a single high-energy photon.

PMID- 9909477
TI  - Absolute low-energy experimental cross sections for (e,2e) processes on helium.

PMID- 9909479
TI  - Electric-field ionization of high Rydberg states and vertical ionization
      potential of an impurity in dense fluid argon.

PMID- 9909480
TI  - Comparison of trap-loss collision spectra for 85Rb and 87Rb.

PMID- 9909481
TI  - Enhancement of charge capture from a laser-excited target by highly charged ions.

PMID- 9909482
TI  - Optical double layers.

PMID- 9909483
TI  - Quantum-nondemolition measurements and the "collapse of the wave function"

PMID- 9909485
TI  - Quantum recurrence in a quasibound system.

PMID- 9909484
TI  - Inverse quantum-mechanical control: A means for design and a test of intuition.

PMID- 9909486
TI  - Perspective of Einstein-Podolsky-Rosen spin correlations in the phase-space
      formulation for arbitrary values of the spin.

PMID- 9909487
TI  - Meaning of the wave function.

PMID- 9909488
TI  - Testing quantum mechanics against a full set of Bell inequalities.

PMID- 9909489
TI  - Testing Lorentz invariance with atomic-beam interferometry.

PMID- 9909491
TI  - Classical-quantum correspondence in the driven surface-state-electron model.

PMID- 9909490
TI  - Continuous-variable representation of dynamic groups in quantum systems. II. The
      extreme-eigenstate approach.

PMID- 9909492
TI  - Loss of coherence in interferometry.

PMID- 9909493
TI  - Quantum interference and determination of the traversal time.

PMID- 9909494
TI  - Pair interactions of rare-gas atoms as a test of exchange-energy-density
      functionals in regions of large density gradients.

PMID- 9909496
TI  - Fock-space coupled-cluster method: The (1,2) sector.

PMID- 9909495
TI  - Muon-catalyzed dd fusion between 25 and 150 K: Theoretical analysis.

PMID- 9909498
TI  - Propagator for the delta -function potential moving with constant velocity.

PMID- 9909497
TI  - Doubly excited ridge states of atoms.

PMID- 9909499
TI  - Second-order magnetic contributions to the hyperfine splitting of the 5snd 1D2
      states in 87Sr.

PMID- 9909501
TI  - Circularly polarized microwave ionization of hydrogen.

PMID- 9909500
TI  - Pseudoconvexity of the atomic electron density: A numerical study.

PMID- 9909502
TI  - Numerical method for the calculation of two-center integrals.

PMID- 9909503
TI  - Tunneling through a one-dimensional potential barrier.

PMID- 9909505
TI  - Dielectronic recombination coefficients for Ni-like tantalum.

PMID- 9909504
TI  - Production of neutral fragments from the dissociation of fast H3+ ions.

PMID- 9909506
TI  - Dissipation effects on wave packets in level crossings: A comparison between two
      numerical approaches.

PMID- 9909507
TI  - Absolute cross sections for electron-impact single ionization of Si+ and Si2+

PMID- 9909508
TI  - Polarization of Fe XXV 1s2-1s2l lines: Collisional resonances and radiative
      cascade contributions to 1s2l magnetic-sublevel excitation rates.

PMID- 9909510
TI  - Photoionization cross-section calculation of atomic tungsten.

PMID- 9909509
TI  - Calculation of the resonant ionization of helium.

PMID- 9909511
TI  - Propensity rules for magnetic-substate distributions for electron capture from
      excited states of atoms by multiply charged ions.

PMID- 9909513
TI  - Double ionization of He by high-energy photon impact.

PMID- 9909512
TI  - Reaction processes in a He2+( 2 Pi u-->A 2 Sigma g+) flash lamp.

PMID- 9909515
TI  - Parity-violation effects on the Auger-electron emission from highly charged
      atomic ions.

PMID- 9909514
TI  - Photoionization from 1sns 1,3Se states of helium.

PMID- 9909516
TI  - Dielectronic recombination from the ground state of heliumlike carbon ions.

PMID- 9909518
TI  - Hyperspherical approach to double-electron excitation of He by fast-ion impact.
      IV. Excitation to the (2l,3l') and (3l,3l') manifolds by multiply-charged-ion
      impact.

PMID- 9909517
TI  - Electron correlation in the 4d hole state of Ba studied by Auger and
      photoelectron spectroscopy.

PMID- 9909519
TI  - Predissociation of H2 in the 3p pi D 1 Pi u+ state.

PMID- 9909521
TI  - High-resolution quantum-beat and rf resonance spectroscopy after grazing-ion
      surface scattering and its application in studies of the hyperfine structure of
      stable terms in 14N I, II, and III.

PMID- 9909520
TI  - Alloying effect on K beta -to-K alpha intensity ratios in TixNi1-x and CrxNi1-x
      alloys studied by gamma -ray fluorescence and fast proton ionization.

PMID- 9909522
TI  - Valence-shell photoabsorption spectra of C, Si, Ge, and Sn.

PMID- 9909523
TI  - Constrained calculations in the electron-vibron model and the Born-Oppenheimer
      approximation.

PMID- 9909524
TI  - Line shape, frequency shift, Rabi splitting, and two-photon resonances in four
      level double-resonance spectroscopy with closely spaced intermediate levels.

PMID- 9909526
TI  - Spectroscopy of the 7snf autoionizing states of barium.

PMID- 9909525
TI  - Selective resonant ionization of zirconium isotopes using intermediate-state
      alignment.

PMID- 9909527
TI  - Laser-assisted binary rearrangement collision: e++H-->Ps+p.

PMID- 9909528
TI  - Chirped-light-field atomic-beam splitter for atom interferometry.

PMID- 9909529
TI  - Quantum motion of a charged particle in a Paul trap.

PMID- 9909530
TI  - Two-photon ionization of lithium in the time-dependent Hartree-Fock
      approximation.

PMID- 9909531
TI  - Spectrum of resonance fluorescence and cooling dynamics in quantized one
      dimensional molasses: Effects of laser configuration.

PMID- 9909532
TI  - Nonlinear theory of index enhancement via quantum coherence and interference.

PMID- 9909533
TI  - Inversionless amplification in a multilevel system.

PMID- 9909534
TI  - Optical switching between bistable soliton states of the second kind.

PMID- 9909535
TI  - Generalized Jaynes-Cummings model with an intensity-dependent coupling
      interacting with a quantum group-theoretic coherent state.

PMID- 9909536
TI  - Production of Schrodinger macroscopic quantum-superposition states in a Kerr
      medium.

PMID- 9909537
TI  - Quantum noise in two- and three-level models of the laser.

PMID- 9909538
TI  - Temporal effects in multiphoton ionization of lithium.

PMID- 9909540
TI  - Coherence and elastic scattering in resonance fluorescence.

PMID- 9909539
TI  - Energy migration in molecular aggregates induced by stochastic coupling.

PMID- 9909542
TI  - Phase diffusion, entangled states, and quantum measurements in the micromaser.

PMID- 9909541
TI  - Vacuum-Rabi-splitting-induced transparency.

PMID- 9909543
TI  - Energy shifts of bound states in strong radiation fields.

PMID- 9909544
TI  - Optimal squeezing of molecular wave packets.

PMID- 9909545
TI  - Lie-algebra methods in quantum optics: The Liouville-space formulation.

PMID- 9909547
TI  - Squeezed spin states.

PMID- 9909546
TI  - Chirped four-wave mixing.

PMID- 9909548
TI  - Chaotic stimulated Brillouin scattering in a finite-length medium.

PMID- 9909549
TI  - Squeezed fluctuations of truncated photon operators.

PMID- 9909550
TI  - Correlation-function approach to the momentum diffusion of atoms moving in
      standing waves.

PMID- 9909551
TI  - Application of radiative renormalization to strong-field resonant nonlinear
      optical interactions.

PMID- 9909552
TI  - Stochastic quantum dynamics of a continuously monitored laser.

PMID- 9909554
TI  - Multiple time scales for recurrences of Rydberg states.

PMID- 9909553
TI  - Recoil-free absorption and scattering of light from confined crystalline ionic
      systems.

PMID- 9909556
TI  - Bounds to the central electron-pair density with applications to two-electron
      atoms.

PMID- 9909555
TI  - Possibility of formation of rare-earth negative ions by attachment of f electrons
      to the atomic ground state.

PMID- 9909558
TI  - Rabi oscillation angle and transitions in a micromaser.

PMID- 9909557
TI  - Lowest 3 Delta u state of He2.

PMID- 9909559
TI  - Erratum: Interaction of an electron with a multimode quantized radiation field

PMID- 9909561
TI  - Bound-state self-energy calculation using partial-wave renormalization.

PMID- 9909560
TI  - Strong onset of ionization in slow Xeq+-Xe collisions at very high q.

PMID- 9909562
TI  - Concentration of atomic population in any single-ground-state magnetic sublevel
      in alkali-metal vapors.

PMID- 9909563
TI  - Collisional loss rate in a magneto-optical trap for sodium atoms: Light-intensity
      dependence.

PMID- 9909564
TI  - Far-off-resonance optical trapping of atoms.

PMID- 9909565
TI  - Precise calculation of the Stark shift of the lithium D1 line.

PMID- 9909566
TI  - Space localization and bound-state population in short-pulse resonant multiphoton
      ionization.

PMID- 9909567
TI  - Logical reversibility in quantum-nondemolition measurements.

PMID- 9909569
TI  - Hydrogen negative ion: Semiclassical quantization and weak-magnetic-field effect.

PMID- 9909568
TI  - Femtosecond time-resolved dispersion relations studied with a frequency-domain
      interferometer.

PMID- 9909571
TI  - Complementarity with neutron two-path interferences and separated-oscillatory
      field resonances.

PMID- 9909570
TI  - Dynamics by measurement: Aharonov's inverse quantum Zeno effect.

PMID- 9909573
TI  - Continuum wave functions and phase shifts for the one-electron state of the
      Coulomb two-center problem.

PMID- 9909572
TI  - Statistics of avoided crossings for generic quantum systems.

PMID- 9909574
TI  - Quantum cryptography without conjugate coding.

PMID- 9909575
TI  - Hidden-variable model for the Bohm Einstein-Podolsky-Rosen experiment.

PMID- 9909576
TI  - Classical dynamics of anyons and the quantum spectrum.

PMID- 9909577
TI  - Spectral filtering in neutron interferometry and wave-corpuscle dualism.

PMID- 9909578
TI  - Quantum computers and intractable (NP-complete) computing problems.

PMID- 9909580
TI  - Casimir effect at macroscopic distances.

PMID- 9909579
TI  - Radiative correction to the electron charge density in the hydrogen atom.

PMID- 9909581
TI  - Continuous position measurements and the quantum Zeno effect.

PMID- 9909582
TI  - Sagnac experiment with electrons: Observation of the rotational phase shift of
      electron waves in vacuum.

PMID- 9909584
TI  - Dynamic polarizabilities and van der Waals coefficients of the 2 (1)S and 2 (3)S
      metastable states of helium.

PMID- 9909583
TI  - Wien filter: A wave-packet-shifting device for restoring longitudinal coherence
      in charged-matter-wave interferometers.

PMID- 9909585
TI  - Generalized oscillator-strength calculations for some low-lying excited states of
      H2 using a high-accuracy configuration-interaction wave function.

PMID- 9909587
TI  - Multireference relativistic configuration-interaction calculations for (d+s)n
      transition-metal atomic states: Application to Zr II hyperfine structure.

PMID- 9909586
TI  - Hyperfine-structure studies of Zr II: Experimental and relativistic configuration
      interaction results.

PMID- 9909588
TI  - Approach to perturbation theory for box models.

PMID- 9909589
TI  - Measurement of the positronium 1 (3)S1-2 (3)S1 interval by continuous-wave two
      photon excitation.

PMID- 9909590
TI  - Bound states of the Hulthen and Yukawa potentials.

PMID- 9909592
TI  - Positronium formation using the multichannel Schwinger variational principle.

PMID- 9909591
TI  - Iterated WKB method of normalization and phase shifts of the nonrelativistic
      continuum wave function.

PMID- 9909593
TI  - Expression for overlap integrals of Slater orbitals.

PMID- 9909594
TI  - Oscillator strengths for the transitions in Ca XIII.

PMID- 9909596
TI  - Complex-coordinate calculations of doubly excited 1,3De resonant states of Ps-

PMID- 9909595
TI  - Doubly excited Pe and Do Feshbach resonances in the lithium isoelectronic
      sequence.

PMID- 9909597
TI  - Atomic effects on the ft value for tritium beta decay.

PMID- 9909598
TI  - Role of potential structure in nonadiabatic collisions with applications to
      He++Ne(2p6)-->He++Ne(2p53s) and Na+I-->Na++I-

PMID- 9909599
TI  - Role of potential structure in the collisional excitation of metastable O(1D)
      atoms.

PMID- 9909600
TI  - Excitation cross sections for the ns 2S-->np 2P resonance transitions in Mg+
      (n=3) and Zn+ (n=4) using electron-energy-loss and merged-beams methods.

PMID- 9909602
TI  - Molecular cation NHe2+

PMID- 9909601
TI  - p-wave photodetachment in a static electric field.

PMID- 9909603
TI  - Differential cross sections for inelastic scattering of electrons from atomic
      oxygen.

PMID- 9909604
TI  - Completely L2 integrable method for strong-coupling multichannel photoionization:
      Photoelectron emission of He between the N=3 and 4 thresholds.

PMID- 9909605
TI  - Production of metastable Ar+ ions by electron-impact ionization of Ar measured by
      translational-energy spectroscopy.

PMID- 9909606
TI  - Resonances and alignment effects in Na-Ar fine-structure-changing half
      collisions.

PMID- 9909607
TI  - One-and-a-half-centered expansion method in charge-transfer calculations of
      proton-hydrogen scattering.

PMID- 9909608
TI  - Relativistic cross sections of positron-impact ionization of hydrogenic ions.

PMID- 9909609
TI  - Reaction dynamics of metastable helium molecules and atoms near 4.2 K.

PMID- 9909611
TI  - Multichannel resonance processes: Theory and application to the Auger spectra of
      the CO molecule.

PMID- 9909610
TI  - Differential cross sections for state-selective electron capture by low-energy
      Arq+ ions from He and Ar.

PMID- 9909612
TI  - Inner-shell photoionization of alkaline-earth-metal atoms.

PMID- 9909613
TI  - Detection of two electrons in low-lying continuum states of a single projectile
      ion resulting from the collision of a 10.7-MeV Ag4+ ion with an Ar gas atom.

PMID- 9909615
TI  - Observation of CN A-->X and B-->X emissions in gas-phase collisions of fast O(3P)
      atoms with HCN.

PMID- 9909614
TI  - Electric-field effects on H- photodetachment partial cross sections above 13.4
      eV.

PMID- 9909616
TI  - Application of the advanced adiabatic approach to charge exchange in slow
      collisions between H and O8+

PMID- 9909618
TI  - Parametrization of radiative-recombination cross sections.

PMID- 9909617
TI  - High-resolution photoelectron spectrometric analysis of the decay of the 4p
      excitations in atomic strontium.

PMID- 9909619
TI  - Average energy losses of reflected and transmitted particles in the case of a
      grazing incident beam striking a flat scatterer of finite thickness.

PMID- 9909621
TI  - Adiabatic complex-plane calculations of Rydberg-state broadening by Rb and K
      perturbers.

PMID- 9909620
TI  - Fast-ion-beam laser spectroscopy of CO2+: Laser-induced fluorescence of the A
      tilde 2 Pi u-X-tilde 2 Pi g electronic transition.

PMID- 9909623
TI  - Charge-cloud alignment in the electron-impact excitation of 138Ba(.6s6p 1P1).

PMID- 9909622
TI  - Molecular-bond hardening and dynamics of molecular stabilization and trapping in
      intense laser pulses.

PMID- 9909624
TI  - Bremsstrahlung in laser-assisted scattering.

PMID- 9909625
TI  - Magnetic-field-enhanced spontaneous two-photon emission of hydrogenic atoms.

PMID- 9909626
TI  - Electrostatic modes of ion-trap plasmas.

PMID- 9909627
TI  - Calculation of the scattering length in atomic collisions using the semiclassical
      approximation.

PMID- 9909628
TI  - Three-dimensional relativistic model of a bound particle in an intense laser
      field. II.

PMID- 9909629
TI  - Polarization-dependent frequency shifts from Rb-3He collisions.

PMID- 9909630
TI  - Mode entanglement in nondegenerate down-conversion with quantized pump.

PMID- 9909631
TI  - Generation of high-order harmonics from inertially confined molecular ions.

PMID- 9909633
TI  - Soliton trapping and daughter waves in the Manakov model.

PMID- 9909632
TI  - Single-mode-laser phase dynamics.

PMID- 9909634
TI  - Effective two-dimensional model for CO2 lasers.

PMID- 9909635
TI  - Strong self-focusing in nematic liquid crystals.

PMID- 9909636
TI  - Observation of coherence transfer by electron-electron correlation.

PMID- 9909637
TI  - Quantitative study of multiphoton multiple ionization: Second-harmonic Nd:YAG
      laser ionization of the doubly excited 2p2 3P bound state of H-

PMID- 9909638
TI  - Local and global effects of boundaries on optical-pattern formation in Kerr
      media.

PMID- 9909639
TI  - Schrodinger-cat states of the electromagnetic field and multilevel atoms.

PMID- 9909641
TI  - Radiation emitted by a resonantly driven hydrogen atom.

PMID- 9909640
TI  - Paraxial wave optics and harmonic oscillators.

PMID- 9909642
TI  - Antiphase dynamics of multimode intracavity second-harmonic generation.

PMID- 9909643
TI  - Laser-amplifier gain and noise.

PMID- 9909645
TI  - Gain-guiding effects in an amplifier with focused gain.

PMID- 9909644
TI  - Frequency-domain measurement of quantum beats.

PMID- 9909646
TI  - Theory of a multimode quasiequilibrium semiconductor laser.

PMID- 9909647
TI  - Classical entropy of quantum states of light.

PMID- 9909648
TI  - Quantum optical master equations: The one-atom laser.

PMID- 9909649
TI  - First-order-like transition for colored-noise saturation models of dye lasers.

PMID- 9909650
TI  - Classical and quantum stabilization of atoms in intense laser fields.

PMID- 9909651
TI  - Canonical transformations to action and phase-angle variables and phase
      operators.

PMID- 9909652
TI  - Spectral linewidth narrowing in a strongly coupled atom-cavity system via
      squeezed-light excitation of a "vacuum" Rabi resonance.

PMID- 9909653
TI  - Laser-induced photonic-continuum structure.

PMID- 9909654
TI  - Quantum-nondemolition measurements using dissipative atom-field coupling: Monte
      Carlo wave-function approach.

PMID- 9909655
TI  - Control of tunneling in an electromagnetic cavity.

PMID- 9909656
TI  - Generalization of an efficient procedure for calculating the evolution of the
      wave function of a system interacting with a short laser pulse.

PMID- 9909657
TI  - Multistability in mesoscopic Rydberg-atom systems.

PMID- 9909658
TI  - Calculation of the micromaser spectrum. I. Green's-function approach and
      approximate analytical techniques.

PMID- 9909659
TI  - Calculation of the micromaser spectrum. II. Eigenvalue approach.

PMID- 9909660
TI  - scrL2 stabilization theory of dynamics: Dissociative photoabsorption.

PMID- 9909661
TI  - General method for deforming quantum dynamics into classical dynamics while
      keeping

PMID- 9909663
TI  - Hyperfine-interaction constants of the 8D3/2 state in 85Rb using quantum-beat
      spectroscopy.

PMID- 9909662
TI  - Dipole moment, polarizability, and their derivatives for the SiC molecule.

PMID- 9909664
TI  - Interelectronic moments of atomic systems.

PMID- 9909665
TI  - Connection between superelastic and inelastic electron-atom collisions involving
      polarized collision partners.

PMID- 9909666
TI  - Measurement of the 6p1/2 epsilon l branching ratios of the (6pns)J=1 state of
      barium.

PMID- 9909668
TI  - Adiabatic population transfer in a multilevel system.

PMID- 9909667
TI  - Very narrow doubly excited 2(1,0)-n and 2(-1,0)0n 1Po states of helium.

PMID- 9909669
TI  - Learning about non-Markovian effects by degenerate four-wave-mixing processes.

PMID- 9909670
TI  - Comment on "Regular and chaotic motions in ion traps: A nonlinear analysis of
      trap equations"

PMID- 9909671
TI  - Comment on "Regular and chaotic motions in ion traps: A nonlinear analysis of
      trap equations"

PMID- 9909672
TI  - Reply to Comments on "Regular and chaotic motions in ion traps: A nonlinear
      analysis of trap equations"

PMID- 9909673
TI  - Erratum: Absolute optical oscillator strengths for the electronic excitation of
      atoms at high resolution. III. The photoabsorption of argon, krypton, and xenon

PMID- 9909674
TI  - Erratum: Multiphoton ionization in superintense, high-frequency laser fields. I.
      General developments

PMID- 9909675
TI  - Nuclear-structure correction to the Lamb shift.

PMID- 9909677
TI  - Multipole structure in asymmetrical double Rydberg states.

PMID- 9909676
TI  - Information-theoretic limits to quantum cryptography.

PMID- 9909678
TI  - Hyperfine populations prior to muon capture.

PMID- 9909679
TI  - Energy corrections of order mc2 alpha 6ln alpha in helium.

PMID- 9909680
TI  - Near-threshold continuum structure and the dissociation energies of H2, HD, and
      D2.

PMID- 9909681
TI  - Three-body distorted-wave Born approximation for electron-atom ionization.

PMID- 9909682
TI  - Surface-induced pressure-gradient formation in a gas mixture.

PMID- 9909684
TI  - Superluminal (but causal) propagation of wave packets in transparent media with
      inverted atomic populations.

PMID- 9909683
TI  - Polarization gradient cooling of a trapped ion.

PMID- 9909686
TI  - X-ray laser with photon energy of about 10 keV.

PMID- 9909685
TI  - Field-induced resonances in four-wave mixing.

PMID- 9909687
TI  - Adiabatic stabilization of excited states of H in an intense linearly polarized
      laser field.

PMID- 9909689
TI  - Quantum dynamical model for wave-function reduction in classical and macroscopic
      limits.

PMID- 9909688
TI  - Dispersive profiles in resonance fluorescence of a two-level atom in a squeezed
      vacuum.

PMID- 9909690
TI  - Structure of Berry's phase: Some group-theoretical examples.

PMID- 9909691
TI  - Ways to describe dynamical state-vector reduction.

PMID- 9909693
TI  - Dipole-dipole interaction of two excited hydrogen atoms.

PMID- 9909692
TI  - Adiabatic motion of a neutral spinning particle in an inhomogeneous magnetic
      field.

PMID- 9909694
TI  - Supersymmetry and a time-dependent Landau system.

PMID- 9909696
TI  - Non-Boolean derived logics for classical systems.

PMID- 9909695
TI  - Quantum chaos of the hydrogen atom in a generalized van der Waals potential.

PMID- 9909698
TI  - Quantum tunneling in dissipative systems.

PMID- 9909697
TI  - Effects of anharmonicity on nonclassical states of the time-dependent harmonic
      oscillator.

PMID- 9909699
TI  - Analytic solution for the dissipative anharmonic quantum oscillator and
      semiclassical analysis.

PMID- 9909700
TI  - Franson's experiment using polarized photons.

PMID- 9909701
TI  - Complementarity of one-particle and two-particle interference.

PMID- 9909702
TI  - Models for local Ohmic quantum dissipation.

PMID- 9909703
TI  - Qualitative study of a model three-level Hamiltonian with SU(3) dynamical
      symmetry.

PMID- 9909705
TI  - Wave mechanics of particle detectors.

PMID- 9909704
TI  - Supersqueezed states.

PMID- 9909707
TI  - Interaction of light with an accelerating dielectric.

PMID- 9909706
TI  - Macroscopic limit of a solvable dynamical model.

PMID- 9909708
TI  - Exact supersymmetry in the nonrelativistic hydrogen atom.

PMID- 9909709
TI  - Analysis of the Thouless coherent state using the 1/K expansion.

PMID- 9909710
TI  - Interaction of Ar17+ ions on metallic surfaces at grazing incidence.

PMID- 9909712
TI  - Measurements of radiative-decay rates of the 2s22p(2P degrees)-2s2p2(4P)
      intersystem transitions of C+

PMID- 9909711
TI  - Relativistic variational calculations with finite nuclear size: Application to
      hydrogenic atoms in strong magnetic fields.

PMID- 9909713
TI  - Differential electron emission for isotachic H+ and He2+ impact on helium.

PMID- 9909714
TI  - Effects of relativity and M2 transitions on the resonance contributions to
      electron-impact ionization of highly charged Li-like ions.

PMID- 9909715
TI  - Compton scattering of photons from bound electrons: Full relativistic independent
      particle-approximation calculations.

PMID- 9909716
TI  - Ab initio calculation of scattering length and cross sections at very low
      energies for electron-helium scattering.

PMID- 9909717
TI  - Stabilized double-electron capture in Krq+ (q=17,18)-Kr collisions.

PMID- 9909718
TI  - Production of free electron-positron pairs in relativistic heavy-ion collisions.

PMID- 9909720
TI  - Threshold-energy region in the electron-excitation cross sections of the sodium
      resonant transition.

PMID- 9909719
TI  - Velocity dependence of absolute cross sections for charge capture by Ar7+ from
      ground-state and excited-state sodium.

PMID- 9909721
TI  - Coplanar asymmetric (e,2e) experiments on xenon 4d and 5p orbitals.

PMID- 9909722
TI  - Fast negative helium ions produced by double electron capture in single He+-He
      collisions.

PMID- 9909723
TI  - K-shell ionization of atoms by electron and positron impact.

PMID- 9909724
TI  - Vibrational-excitation cross sections of molecular oxygen by electron impact.

PMID- 9909726
TI  - Photodetachment of H- with excitation to H(N=2).

PMID- 9909725
TI  - Muonium atom spin exchange with alkali-metal vapors: Mu+Cs.

PMID- 9909727
TI  - Excitation of the copper resonance lines by low-energy electrons.

PMID- 9909728
TI  - Extensive L2 calculation of partial photoionization cross sections of He in the
      4lnl' resonance region.

PMID- 9909729
TI  - Inelastic electron-dipole-molecule scattering at sub-milli-electron-volt
      energies: HF and NH3.

PMID- 9909730
TI  - Ion-collision spectrometric study of the dissociation dynamics of S2+ and CS+
      radicals.

PMID- 9909731
TI  - Theory of the angle-dependent autoionization cross section in ion-atom
      collisions.

PMID- 9909732
TI  - Double photoionization of helium using many-body perturbation theory.

PMID- 9909733
TI  - Effects of channel interaction, exchange, and relaxation on the angular
      distribution and spin polarization of Auger electrons from noble-gas atoms.

PMID- 9909734
TI  - Double electron capture in Ne8+-He collisions at intermediate energies.

PMID- 9909735
TI  - Double electron capture and the angular distribution of ejected electrons in Ne8+
      He collisions.

PMID- 9909736
TI  - Thick-target external-bremsstrahlung spectra of 147Pm and 35S beta rays.

PMID- 9909737
TI  - W value in liquid krypton.

PMID- 9909738
TI  - Estimation of the ground-state potentials of alkali-metal diatomic molecules with
      the use of the multiparameter generalized reduced-potential-curve method.

PMID- 9909739
TI  - KL edges in x-ray-absorption spectra of third-period atoms: Si, P, S, and Cl.

PMID- 9909740
TI  - Binding energy, microstructure, and shell model of Coulomb clusters.

PMID- 9909741
TI  - Alignment in two-step pulsed laser excitation of Rydberg levels in light atoms:
      The example of sodium.

PMID- 9909742
TI  - Comparison of kinetic-energy distributions and ionic fragment yields of CO2 and
      N2O arising from Coulomb explosions induced by multiphoton ionization and fast
      ion impact.

PMID- 9909743
TI  - Sensitive measurement of phase shifts due to the ac Stark effect in a Ca optical
      Ramsey interferometer.

PMID- 9909745
TI  - Probe transmission in a one-dimensional optical molasses: Theory for circularly
      cross-polarized cooling beams.

PMID- 9909744
TI  - Nonlinear ring structures in forward scattering of resonant monochromatic laser
      radiation.

PMID- 9909746
TI  - Population trapping in a Raman-coupled model interacting with a two-mode
      quantized cavity field.

PMID- 9909747
TI  - Direct measurement of velocity-changing collision cross sections by laser optical
      pumping.

PMID- 9909748
TI  - Quasiclassical analysis of laser cooling by velocity-selective coherent
      population trapping.

PMID- 9909749
TI  - Quantum suppression of collisional loss rates in optical traps.

PMID- 9909750
TI  - Laser cooling of trapped ions with polarization gradients.

PMID- 9909751
TI  - Billiard balls and matter-wave interferometry.

PMID- 9909752
TI  - Optical spectra from a degenerate optical parametric oscillator coupling with N
      two-level atoms.

PMID- 9909753
TI  - Dynamics of coherently pumped lasers with linearly polarized pump and generated
      fields.

PMID- 9909755
TI  - Rate equations between electronic-state manifolds.

PMID- 9909754
TI  - Multiphoton and tunnel ionization by an optical field with polar asymmetry.

PMID- 9909756
TI  - Observation of extreme sensitivity to induced molecular coherence in stimulated
      Raman scattering.

PMID- 9909758
TI  - Quantum-nondemolition schemes to measure quadrature phases using intracavity
      harmonic generation.

PMID- 9909759
TI  - Interferometers and minimum-uncertainty states.

PMID- 9909760
TI  - Effect of finite Q on squeezed states in a micromaser.

PMID- 9909757
TI  - Squeezing induced in a harmonic oscillator by a sudden change in mass or
      frequency.

PMID- 9909761
TI  - Theoretical description of two-photon phase conjugation in polar molecules.

PMID- 9909763
TI  - Two-photon absorption and nonclassical states of light.

PMID- 9909762
TI  - Laser Ginzburg-Landau equation and laser hydrodynamics.

PMID- 9909765
TI  - Effects of atomic coherences in the Jaynes-Cummings model: Photon statistics and
      entropy.

PMID- 9909764
TI  - Theory of radiation forces and momenta for mobile atoms in light fields.

PMID- 9909767
TI  - Gap solitary waves with gain and two-photon absorption.

PMID- 9909766
TI  - Transverse instabilities in the polarizations and intensities of
      counterpropagating light waves.

PMID- 9909768
TI  - Laser second threshold: Its exact analytical dependence on detuning and
      relaxation rates.

PMID- 9909769
TI  - Laser-noise suppression in the dressed-atom approach. I. Fluctuations in a
      regularly pumped laser.

PMID- 9909770
TI  - Laser-noise suppression in the dressed-atom approach. II. Minimization principle
      for conventionally pumped lasers.

PMID- 9909772
TI  - Quantum random walks.

PMID- 9909771
TI  - Common dynamics of the differential-flow-induced chemical instability and the
      multimode instability in a laser with a saturable absorber.

PMID- 9909773
TI  - Calculation of hyperfine coupling constants of radicals by density-functional
      theory.

PMID- 9909775
TI  - Spin asymmetry in resonant electron-hydrogen elastic scattering.

PMID- 9909774
TI  - n=2 to n=1 forbidden transitions in H-like and He-like silver and niobium.

PMID- 9909776
TI  - Linear polarization of L alpha 1 and L alpha 2 x-ray lines of gold.

PMID- 9909777
TI  - Force of radiation on a two-level atom near a small dielectric.

PMID- 9909778
TI  - Exchange force in the near-resonant Kapitza-Dirac effect.

PMID- 9909779
TI  - Origin of "fast electrons" from slow atomic collisions.

PMID- 9909780
TI  - Reply to "Origin of 'fast electrons' from slow atomic collisions"

PMID- 9909781
TI  - Comment on "Further investigations of the operationally defined quantum phase"

PMID- 9909782
TI  - Reply to "Comment on 'Further investigations of the operationally defined quantum
      phase' "

PMID- 9909783
TI  - Angle-resolved photoelectron spectroscopy of Ca in the 3p-3d giant-resonance
      region.

PMID- 9909784
TI  - High-efficiency single-photon detectors.

PMID- 9909785
TI  - Green-function approach to electron angular correlations in the Wannier threshold
      law.

PMID- 9909786
TI  - Double ionization of helium by a single photon with energy 89-140 eV.

PMID- 9909787
TI  - Magneto-optical trapping of metastable xenon: Isotope-shift measurements.

PMID- 9909788
TI  - Quadratic collisional loss rate of a 7Li trap.

PMID- 9909789
TI  - Two-level system in a strong laser field: A comparative analysis between the
      Landau-Lifshitz solution and an exact numerical one.

PMID- 9909790
TI  - Experimental determination of quantum-phase distributions using optical homodyne
      tomography.

PMID- 9909791
TI  - Double ionization in the perturbative and tunneling regimes.

PMID- 9909792
TI  - General form of the Dirac quantum-defect theory.

PMID- 9909793
TI  - Quantum chaos in the configurational quantum cat map.

PMID- 9909794
TI  - Observation of the scalar Aharonov-Bohm effect by neutron interferometry.

PMID- 9909795
TI  - Quantum mechanics in terms of discrete beables.

PMID- 9909796
TI  - Semiclassical periodic-orbit theory for identical particles.

PMID- 9909798
TI  - General method for determining the Floquet states of the forced rotor and other
      anharmonic systems.

PMID- 9909797
TI  - Self-consistent frequencies of the electron-photon system.

PMID- 9909799
TI  - Semiclassical approach to quantum-mechanical problems with broken supersymmetry.

PMID- 9909801
TI  - Fermions near two-dimensional surfaces.

PMID- 9909800
TI  - Interference in a spherical phase space and asymptotic behavior of the rotation
      matrices.

PMID- 9909802
TI  - Relativistic classical limit of quantum theory.

PMID- 9909803
TI  - Lamb-shift measurement in hydrogenic phosphorus.

PMID- 9909804
TI  - Energy functionals in momentum space: Exchange energy, quantum corrections, and
      the Kohn-Sham scheme.

PMID- 9909806
TI  - Delayed-detection measurement of atomic Na 3p 2P3/2 hyperfine structure using
      polarization quantum-beat spectroscopy.

PMID- 9909805
TI  - Nonadiabatic variational calculations for the ground state of the positronium
      molecule.

PMID- 9909808
TI  - Rational potential using a modified Hill determinant method.

PMID- 9909807
TI  - Finite-element calculations for the S states of helium.

PMID- 9909809
TI  - Two-photon decay of the 2 (1)S0 state in He-like bromine.

PMID- 9909811
TI  - Energies, fine structures, and isotope shifts of the 1s22snl excited states of
      the beryllium atom.

PMID- 9909810
TI  - Calculation of the defect kinetic energy in Kohn-Sham theory by means of local
      scaling transformations.

PMID- 9909812
TI  - Single- and double-photoionization cross sections of nitric oxide (NO) and ionic
      fragmentation of NO+ and NO2+

PMID- 9909814
TI  - Method for calculating the electron-impact ionization of ions of any complexity.

PMID- 9909813
TI  - Alignment of magnetic substates in double-electron-capture collisions.

PMID- 9909815
TI  - Photodetachment and autodetachment of the Be- ion.

PMID- 9909817
TI  - Low-temperature radiative recombination of electrons with bare nuclei.

PMID- 9909816
TI  - Polarization and intensity spectra for Mg-Ne and Mg-Ar fractional collisions.

PMID- 9909819
TI  - Soft-electron emission peak in ion-helium collisions.

PMID- 9909820
TI  - Enhanced spin polarization of elastic electron scattering from alkaline-earth
      metal atoms in Ramsauer-Townsend and low-lying shape resonance regions.

PMID- 9909818
TI  - Calculation of the cross section for e+-e- (K orbit) pairs by very-high-energy
      fully stripped heavy ions at perturbational impact parameters.

PMID- 9909821
TI  - Photodissociation spectroscopy of Mg2+ (1 Sigma 2u+-1 Sigma 2g+).

PMID- 9909822
TI  - Nonperturbative pair production by a Dirac square well with time-dependent depth.

PMID- 9909824
TI  - Combined effect of relaxation and channel interaction on outer-shell
      photoionization in Ar, K+, and Ca2+

PMID- 9909823
TI  - Phase-equivalent potentials for arbitrary modifications of the bound spectrum.

PMID- 9909826
TI  - Direct numerical approach to electron-hydrogen scattering.

PMID- 9909825
TI  - High-angular-momentum transfer during the autoionization of the 6p1/2nd J=3
      states of barium.

PMID- 9909827
TI  - Rutherford backscattering from a thick target.

PMID- 9909829
TI  - Auger-electron spectroscopy of molecules: Circular dichroism following
      photoabsorption in rotating linear molecules.

PMID- 9909828
TI  - Testing the validity of the optical diffusion coefficient: Line-shape
      measurements of CO perturbed by N2.

PMID- 9909830
TI  - Double-electron excitation channels at the L edges of atomic Hg.

PMID- 9909831
TI  - Optical spin polarization and state-sensitive detection of a cesium atomic beam.

PMID- 9909832
TI  - Interaction of atoms with a magneto-optical potential.

PMID- 9909833
TI  - Photoabsorption spectra of atoms in parallel electric and magnetic fields.

PMID- 9909834
TI  - Laser cooling of stored high-velocity ions by means of the spontaneous force.

PMID- 9909835
TI  - Molecular stabilization and angular distribution in photodissociation of H2+ in
      intense laser fields.

PMID- 9909836
TI  - Polarization effects on the two-photon dissociation of HD+ with two radiation
      fields in the presence of one and two intermediate resonant states.

PMID- 9909837
TI  - Cooling or heating of atoms by radiatively assisted inelastic collisions.

PMID- 9909838
TI  - Spectrum of resonance fluorescence from a single trapped ion.

PMID- 9909839
TI  - Neutralization of slow multicharged ions at a clean gold surface: Total electron
      yields.

PMID- 9909841
TI  - Higher-order squeezing for the quantized light field: Kth-power amplitude
      squeezing.

PMID- 9909840
TI  - Neutralization of slow multicharged ions at a clean gold surface: Electron
      emission statistics.

PMID- 9909842
TI  - Coherent states on a circle and quantum interference.

PMID- 9909843
TI  - Effects of ion pairs on the dynamics of erbium-doped fiber lasers.

PMID- 9909844
TI  - Squeezing in an injection-locked semiconductor laser.

PMID- 9909845
TI  - Amplitude squeezing from spectral-hole burning: A semiclassical theory.

PMID- 9909846
TI  - Impurity modes in one-dimensional periodic systems: The transition from photonic
      band gaps to microcavities.

PMID- 9909847
TI  - Type-III intermittency in a four-level coherently pumped laser.

PMID- 9909848
TI  - Gain due to level-dependent collisions.

PMID- 9909849
TI  - Effect of atomic decay in degenerate two-photon micromasers.

PMID- 9909850
TI  - Microwave forced autoionization of Na2 Rydberg states.

PMID- 9909851
TI  - Generalized Jaynes-Cummings models with a time-dependent atom-field coupling.

PMID- 9909852
TI  - External photodetection of cavity radiation.

PMID- 9909853
TI  - Persistent properties of period doubling in directly modulated semiconductor
      lasers.

PMID- 9909855
TI  - Phase distribution and linewidth in the micromaser.

PMID- 9909854
TI  - Spatiotemporal instabilities in a Fabry-Perot resonator filled with sodium vapor.

PMID- 9909856
TI  - Nonlinear dynamics in single-mode optical resonators.

PMID- 9909857
TI  - Effect of pressure-dependent quantum interference on the ac Stark shifting of two
      photon resonances.

PMID- 9909858
TI  - Conditions leading to intense low-frequency generation and strong localization in
      two-level systems.

PMID- 9909860
TI  - Quantum-mechanical stability of solitons and the correspondence principle.

PMID- 9909859
TI  - Instability hierarchies in self-pulsing lasers.

PMID- 9909861
TI  - Bichromatic wave propagation in periodically poled media.

PMID- 9909862
TI  - Many-body quantum theory of the optical parametric oscillator.

PMID- 9909863
TI  - Monte Carlo calculations of radiation from a randomly modulated atom in a strong
      field.

PMID- 9909864
TI  - Nonclassical vibrational states in a quantized trap.

PMID- 9909865
TI  - Photon statistics of a two-mode squeezed vacuum.

PMID- 9909867
TI  - Resonant two-color detachment of H- with excitation of H(n=2).

PMID- 9909866
TI  - Multiphoton ejection of strongly bound relativistic electrons in very intense
      laser fields.

PMID- 9909868
TI  - Transient statistics for two-mode gas ring lasers.

PMID- 9909869
TI  - Large quadrature squeezing at high intensities.

PMID- 9909870
TI  - Harmonic generation in ionizing systems by the complex scaled adiabatic-switch
      method.

PMID- 9909872
TI  - Disappearance and reappearance of macroscopic quantum interference.

PMID- 9909871
TI  - Effects of Zeeman degeneracy on the steady-state properties of an atom
      interacting with a near-resonant laser field: Analytic results.

PMID- 9909873
TI  - Multichannel-quantum-defect-theory analysis of natural radiative lifetimes in the
      perturbed Rydberg sequence 4f146snp 3P2 of Yb I.

PMID- 9909874
TI  - Core-polarization effects for the intercombination and resonance transitions in
      Cd-like ions.

PMID- 9909875
TI  - Electron-pair logarithmic convexity and interelectronic moments in atoms:
      Application to heliumlike ions.

PMID- 9909877
TI  - Cross sections of e--O scattering at intermediate and high energies (Ei=8.7-1000
      eV).

PMID- 9909876
TI  - Theoretical determination of the spectroscopic constants of CaH+

PMID- 9909878
TI  - Double ionization of O2 by electron impact.

PMID- 9909879
TI  - Theory of light-induced viscous flow in a gas.

PMID- 9909880
TI  - Theory of the Rydberg-atom one-photon micromaser.

PMID- 9909881
TI  - Series representation of quantum-field quasiprobabilities.

PMID- 9909882
TI  - Nonlinear features of a micromaser in the semiclassical limit.

PMID- 9909884
TI  - Calculations of high-order-harmonic generation in the strongly ionizing regime.

PMID- 9909883
TI  - Spontaneous emission into an electromagnetically induced transparency.

PMID- 9909885
TI  - Quantum tunneling in a Kerr medium with parametric pumping.

PMID- 9909886
TI  - Comment on "Wave-function collapse by measurement and its simulation"

PMID- 9909887
TI  - Reply to "Comment on 'Wave-function collapse by measurement and its simulation' "

PMID- 9909889
TI  - Reply to "Comment on 'Computational approach to the quantum Zeno effect: Position
      measurements' "

PMID- 9909888
TI  - Comment on "Computational approach to the quantum Zeno effect: Position
      measurements"

PMID- 9909891
TI  - Erratum: Interaction of radiation with matter: Integrable problems

PMID- 9909890
TI  - Erratum: Comparative analysis of the threshold behavior of two-electron escape in
      electron-impact ionization of valence-1 atoms

PMID- 9909893
TI  - Exact fixed-angle spinor evolutions via the rotating-frame formalism.

PMID- 9909892
TI  - Resonant width and energy determined by photoionization from excited divalent
      atoms.

PMID- 9909894
TI  - Probing electron correlations in double photoionization of He at intermediate
      energies.

PMID- 9909896
TI  - Short-pulse detachment of H- in the presence of a static electric field.

PMID- 9909895
TI  - Angular dependence of the neutral fraction of medium-energy hydrogen emerging
      from NiSi2(111).

PMID- 9909897
TI  - Observation of enhanced emission of cusp electrons at impact of excited
      metastable neutral He projectiles.

PMID- 9909899
TI  - Line strengths in vibrational spectra of a two-dimensional optical crystal.

PMID- 9909898
TI  - Blue shift of the Mie plasma frequency in Ag clusters and particles.

PMID- 9909901
TI  - Quantum amplification with correlated quantum fields.

PMID- 9909900
TI  - Prediction of a deterministic melting transition of two-ion crystals in a Paul
      trap.

PMID- 9909902
TI  - Theory of quantum beat and polarization interference in four-wave mixing.

PMID- 9909903
TI  - Landau-level ground-state degeneracy and its relevance for a general quantization
      procedure.

PMID- 9909904
TI  - Optimal control of classical systems with explicit quantum-classical-difference
      reduction.

PMID- 9909906
TI  - Exact Green's function for the step and square-barrier potentials.

PMID- 9909905
TI  - Random perturbation of systematic degeneracies and their Fourier transforms and
      periodic orbits.

PMID- 9909907
TI  - Quantum-mechanical motion of Gaussian wave packets on elliptical and hyperbolic
      Kepler orbits in the Coulomb field.

PMID- 9909908
TI  - Generalized Coleman-Hepp model and quantum coherence.

PMID- 9909909
TI  - Non-Abelian geometric effect in quantum adiabatic transitions.

PMID- 9909910
TI  - Contributions to the binding, two-loop correction to the Lamb shift.

PMID- 9909911
TI  - Evaluation of two-photon exchange graphs for highly charged heliumlike ions.

PMID- 9909912
TI  - Quantum behavior of general time-dependent quadratic systems linearly coupled to
      a bath.

PMID- 9909913
TI  - Single-transverse-photon contributions of order alpha 6ln ( alpha ) to the energy
      levels of positronium.

PMID- 9909914
TI  - Dimensional perturbation theory for excited states of two-electron atoms.

PMID- 9909915
TI  - Electronic structure of the CoO molecule.

PMID- 9909916
TI  - Dynamic polarizabilities and Rydberg states of the argon isoelectronic sequence.

PMID- 9909917
TI  - Density-functional calculations of electric-dipole polarizabilities for atoms.

PMID- 9909918
TI  - Fully numerical relativistic calculations for diatomic molecules using the finite
      element method.

PMID- 9909919
TI  - Hartree-Fock method posed as a density-functional theory: Application to the Be
      atom.

PMID- 9909921
TI  - Lower bound on the ground-state energy and one-dimensional N-fermion problem.

PMID- 9909920
TI  - Exact quantum theory of a time-dependent bound quadratic Hamiltonian system.

PMID- 9909922
TI  - Forbidden transitions in one- and two-electron nickel.

PMID- 9909924
TI  - Sternheimer free determination of the 59Co nuclear quadrupole moment from
      hyperfine-structure measurements.

PMID- 9909923
TI  - Induced mapping in the n-electron space and a transformation of valence-bond
      structures to molecular-orbital functions.

PMID- 9909925
TI  - Lifetimes and Rydberg-valence state mixing of the c' 1 Sigma g+(v=4) and 1 Pi
      u(v=4) states of N2.

PMID- 9909926
TI  - Accurate vacuum-polarization calculations.

PMID- 9909927
TI  - Semiclassical description of antiproton capture on atomic helium.

PMID- 9909928
TI  - New exactly solvable Hamiltonians: Shape invariance and self-similarity.

PMID- 9909930
TI  - Many-body theory of electron scattering by excited atomic targets: Fundamental
      formulas.

PMID- 9909929
TI  - Logarithmic mean excitation energies: II. Helium, lithium, beryllium, and the 2s
      state of hydrogen.

PMID- 9909932
TI  - Algebraic rotating-frame approach to electron-molecule scattering.

PMID- 9909931
TI  - Near-threshold behavior of the 2p-electron excitation in Mg-Mg, Al-Al, and Si-Si
      symmetric collisions.

PMID- 9909933
TI  - Angular distributions in autodetachment from doubly excited O- states.

PMID- 9909934
TI  - Electron-impact ionization of lithiumlike ions: Ti19+, V20+, Cr21+, Mn22+, and
      Fe23+

PMID- 9909935
TI  - Single-particle potential for photoexcited electron orbitals of open-shell atoms.

PMID- 9909936
TI  - Importance of bound-free correlation effects for vibrational excitation of
      molecules by electron impact: A sensitivity analysis.

PMID- 9909937
TI  - Monte Carlo simulation of x-ray absorption and electron drift in gaseous xenon.

PMID- 9909938
TI  - J-mixing process of alkali-metal atoms treated as a three-body process within an
      eikonal approximation.

PMID- 9909939
TI  - Experimental determination of real elements of the density matrix and the dipole
      moment of H(n=3) atoms produced from 20-100-keV H+ on Ar.

PMID- 9909941
TI  - Spin conservation in single-electron capture by N2+ in He, Ne, and Ar.

PMID- 9909940
TI  - Projectile-Auger-electron spectra of C3+ following 12-MeV collisions with He
      targets.

PMID- 9909942
TI  - Use of time-dependent wave-packet theory in electron-molecule scattering.

PMID- 9909944
TI  - Elastic D- and higher-partial-wave phase shifts in positron-hydrogen-atom
      collisions using Schwinger's principle.

PMID- 9909943
TI  - Leading corrections to atomic impulse-approximation Compton profiles: A density
      functional approach.

PMID- 9909945
TI  - Evolution of the anisotropy of the Auger decay of 2p3/2-1ns resonances into
      anisotropy of L3MM Auger decay in Ar.

PMID- 9909946
TI  - Spectrum of the Casimir effect and the Lifshitz theory.

PMID- 9909947
TI  - Electric-field effects on H- photodetachment with excitation of H(n=2).

PMID- 9909948
TI  - Time ordering of two-step processes in energetic ion-atom collisions: Basic
      formalism.

PMID- 9909949
TI  - Time-ordering effects in K-shell excitation of 170-MeV Ne7+ colliding with gas
      atoms: Single excitation.

PMID- 9909950
TI  - Symmetry relations in phase-sensitive magnetic-resonance spectroscopy.

PMID- 9909951
TI  - Observation of molecular emission bands in cw He-Cd+ hollow-cathode lasers.

PMID- 9909952
TI  - Molecular handedness and chiral strength determined by matter-wave circular
      dichroism.

PMID- 9909955
TI  - Effects of the intermolecular interaction on the depolarized rototranslational
      Raman spectra of hydrogen.

PMID- 9909954
TI  - Line mixing and state-to-state rotational relaxation rates in D2 determined from
      the Raman Q branch.

PMID- 9909953
TI  - Observation and analysis of core-penetrating Rydberg states of calcium
      monofluoride.

PMID- 9909956
TI  - Superfluorescence beats in 125Te2 emission.

PMID- 9909957
TI  - Near-threshold double photoionization in Zn and Hg.

PMID- 9909958
TI  - Soft-x-ray spectroscopy of Delta n=0, n=3 transitions in highly stripped lead.

PMID- 9909959
TI  - Deviation from the single-particle model in the angular distribution of thorium
      L3 x rays in proton-impact ionization.

PMID- 9909960
TI  - Steady-state regime for the rotational dynamics of a molecule at the condition of
      quantum chaos.

PMID- 9909961
TI  - Quantum manifestations of order and chaos in the Paul trap.

PMID- 9909962
TI  - Resonance-fluorescence and absorption spectra of a two-level atom driven by a
      strong bichromatic field.

PMID- 9909963
TI  - Parametrically pumped electron oscillators.

PMID- 9909964
TI  - Bifurcations of electronic trajectories and dynamics of electronic Rydberg wave
      packets.

PMID- 9909965
TI  - Double-resonance spectroscopy by a transversely nonuniform pump beam in a three
      level molecular system.

PMID- 9909966
TI  - Theory of second-harmonic generation of molecular systems: The steady-state case.

PMID- 9909967
TI  - Suppression of classical intensity fluctuations via competing nonlinear processes
      in an optical fiber.

PMID- 9909968
TI  - Measurement of number-phase uncertainty relations of optical fields.

PMID- 9909970
TI  - Variation from number- to chaotic-state fields: A generalized geometric state.

PMID- 9909969
TI  - Discriminating field mixtures from macroscopic superpositions.

PMID- 9909972
TI  - Micromaser with Kerr nonlinearity.

PMID- 9909971
TI  - Quantum-noise limits to matter-wave interferometry.

PMID- 9909973
TI  - Two mechanisms for inversionless amplification in four-level atoms with Raman
      pumping.

PMID- 9909975
TI  - Transverse instability of counterpropagating waves in photorefractive media.

PMID- 9909974
TI  - Time-delayed Raman-enhanced nondegenerate four-wave mixing with a broadband laser
      source.

PMID- 9909976
TI  - Index of refraction of a system of strongly driven two-level atoms.

PMID- 9909977
TI  - Phase and squeezing properties of two copropagating fields in a Kerr medium.

PMID- 9909978
TI  - One-dimensional laser cooling with linearly polarized fields.

PMID- 9909980
TI  - Internuclear-axis angular distribution in multiphoton excitation.

PMID- 9909979
TI  - Characteristic oscillations of phase properties for pair coherent states in the
      two-mode Jaynes-Cummings-model dynamics.

PMID- 9909982
TI  - Quantum statistics of a lossless beam splitter: SU(2) symmetry in phase space.

PMID- 9909981
TI  - Four-wave mixing with time-delayed, correlated, phase-diffusing optical fields.

PMID- 9909983
TI  - Helicity dependence of optically encoded second-harmonic generation in glasses.

PMID- 9909984
TI  - Quantum-nondemolition measurement of atomic momentum.

PMID- 9909985
TI  - Superstructures, fractional revivals, and optical Schrodinger-cat states in the
      Jaynes-Cummings model.

PMID- 9909986
TI  - Stimulated Brillouin scattering in fibers with and without external feedback.

PMID- 9909987
TI  - Limits to squeezing and phase information in the parametric amplifier.

PMID- 9909988
TI  - Effect of redistributed radiation on degenerate four-wave mixing.

PMID- 9909989
TI  - Hopf bifurcation at the phase-locking point of an externally driven,
      homogeneously broadened laser.

PMID- 9909990
TI  - Intracavity second-harmonic generation using an electromagnetically induced
      transparency.

PMID- 9909991
TI  - Multimode bosonic realization of the su(1,1) Lie algebra.

PMID- 9909992
TI  - Resonance fluorescence from two identical atoms in a standing-wave field.

PMID- 9909993
TI  - Interaction times in quantum scattering: The sojourn-time-operator approach
      versus the Feynman path-integral approach.

PMID- 9909994
TI  - Quantum violation of stochastic noncontextual hidden-variable theories.

PMID- 9909995
TI  - Lower bounds on equilibrium configurations of diatomic molecular systems.

PMID- 9909996
TI  - Variational close-coupling calculation for D-wave positron-hydrogen scattering.

PMID- 9909998
TI  - Quantum phase distributions of amplified Schrodinger-cat states of light.

PMID- 9909997
TI  - Localization of shadow poles by complex scaling.

PMID- 9909999
TI  - Comment on "Iterative Bogoliubov transformations and anharmonic oscillators"

PMID- 9910000
TI  - Laser-assisted elastic electron-atom collisions.

PMID- 9910001
TI  - Breakdown of the isolated-resonance approximation for the electron-impact
      excitation of positive ions.

PMID- 9910002
TI  - Ultracold photoassociative ionization collisions in a magneto-optical trap: The
      optical-field-intensity dependence in a radiatively dissipative environment.

PMID- 9910003
TI  - Stabilization of Rydberg atoms in superintense laser fields.

PMID- 9910004
TI  - Wavelength dependence of nonsequential double ionization in He.

PMID- 9910005
TI  - Scheme for generation of sub-Poissonian photons: Antibunching of emission events
      by population-dependent spontaneous-emission lifetime in semiconductor
      microcavities.

PMID- 9910006
TI  - Feynman path integral for an infinite potential barrier.

PMID- 9910007
TI  - Relative-state formulation of quantum systems.

PMID- 9910008
TI  - Regions of stability of the nonlinear Schrodinger equation with a potential hill.

PMID- 9910009
TI  - Nonlocal computation in quantum cellular automata.

PMID- 9910011
TI  - Quantum beats in waveguides with time-dependent boundaries.

PMID- 9910010
TI  - Energy levels of the quartic double well using a phase-integral method.

PMID- 9910012
TI  - Canonical generator of conformal transformations in nonrelativistic quantum many
      body systems at finite temperatures.

PMID- 9910013
TI  - Analytical description of some quantum systems with space- and time-periodic
      Hamiltonians.

PMID- 9910015
TI  - Angular-momentum measurement and nonlocality in Bohm's interpretation of quantum
      theory.

PMID- 9910014
TI  - Determination of two-body potentials from n-body spectra.

PMID- 9910016
TI  - Bound states in the continuum from supersymmetric quantum mechanics.

PMID- 9910017
TI  - Simple rule for complex quantum systems.

PMID- 9910018
TI  - Hyperfine-structure measurements of the 151,153Eu+ ground state.

PMID- 9910020
TI  - Two electrons in an external oscillator potential: Particular analytic solutions
      of a Coulomb correlation problem.

PMID- 9910019
TI  - Energy levels and transition amplitudes for alkali-metal atoms in the Brueckner
      approximation.

PMID- 9910022
TI  - Theory and computation of triply excited resonances: Application to states of He-

PMID- 9910023
TI  - Computation of resonances by two methods involving the use of complex
      coordinates.

PMID- 9910021
TI  - Electron-pair analysis for doubly excited ridge states. II. L=1.

PMID- 9910025
TI  - Doubly excited 3Po resonance states of He below the N=2 and N=3 He+ thresholds.

PMID- 9910024
TI  - Levels of the 4p4 configuration of Ge-like Kr V.

PMID- 9910026
TI  - Core-valence correlation on the low-lying 1,3Fo terms of Ca I.

PMID- 9910027
TI  - Model of n coupled generalized deformed oscillators for vibrations of polyatomic
      molecules.

PMID- 9910028
TI  - Velocity dependence of one- and two-electron processes in intermediate-velocity
      Ar16++He collisions.

PMID- 9910029
TI  - Tunneling dynamics in dissipative curve-crossing problems.

PMID- 9910030
TI  - Multiphoton ionization of Mg in the wavelength region of 300-214 nm.

PMID- 9910031
TI  - Relativistic effects on the polarization of line radiation emitted from He-like
      and H-like ions following electron-impact excitation.

PMID- 9910033
TI  - Atomic-electron capture in the presence of a narrow nuclear resonance:
      40Ar(p,p)40Ar reaction.

PMID- 9910032
TI  - Molecular treatment of electron capture in collisions of O5+ ions with H atoms at
      energies from 6 eV/amu to 10 keV/amu: Transfer-excitation processes.

PMID- 9910035
TI  - Radiative recombination and excited-state photoionization of lithium.

PMID- 9910034
TI  - Electron capture in H++N2 collisions.

PMID- 9910036
TI  - Charge exchange between bare beryllium and boron with metastable hydrogen atoms
      at low energies.

PMID- 9910038
TI  - Differential cross sections for the multiple ionization of Ne and Ar by protons.

PMID- 9910037
TI  - Angular distributions for double-electron capture in C4+-He collisions.

PMID- 9910039
TI  - Scattering and (e,2e) reactions in classical s-wave helium.

PMID- 9910040
TI  - Coupled-Sturmian treatment of electron transfer and ionization in proton-neon
      collisions.

PMID- 9910041
TI  - Double photoionization of helium: Use of a correlated two-electron continuum wave
      function.

PMID- 9910043
TI  - Relativistic fermionium production by electrons in a crystal.

PMID- 9910042
TI  - Doubly excited shape resonances in H-

PMID- 9910044
TI  - Electron emission following the interaction of highly charged ions with a Pt(110)
      target.

PMID- 9910045
TI  - Continuum Raman scattering with short laser pulses.

PMID- 9910046
TI  - Hyperfine structure and isotope shift in the far-infrared ground-state
      transitions of atomic oxygen.

PMID- 9910047
TI  - Laser magnetic-resonance measurement of the 3P1-3P2 fine-structure splittings in
      17O and 18O.

PMID- 9910048
TI  - Water-cluster distribution with respect to pressure and temperature in the gas
      phase.

PMID- 9910049
TI  - Spatial distribution of atoms in a magneto-optical trap.

PMID- 9910050
TI  - Semiclassical laser-cooling theory for a trapped multistate ion.

PMID- 9910051
TI  - Experimental evidence of strong-field effects in light-induced collisional energy
      transfer processes in europium and strontium atoms.

PMID- 9910052
TI  - Relativistic corrections to the Zeeman effect in heliumlike atoms.

PMID- 9910053
TI  - Wave-packet dynamics: Level-crossing-induced changes in momentum distributions.

PMID- 9910054
TI  - Collision-enhanced resonance of laser-diode-excited Cs in a buffer gas.

PMID- 9910055
TI  - Optimal control of quantum systems by chirped pulses.

PMID- 9910056
TI  - Harmonic generation by the H2+ molecular ion in intense laser fields.

PMID- 9910057
TI  - Molecular photodissociation with diverging couplings: An application to H2+ in
      intense cw laser fields. I. The single-photon problem.

PMID- 9910058
TI  - Molecular photodissociation with diverging couplings: An application to H2+ in
      intense cw laser fields. II. The multiphoton problem.

PMID- 9910059
TI  - Localization of chaos in the discrete nonlinear Schrodinger equation.

PMID- 9910060
TI  - Amplitude-phase multistability in multiatomic optical systems.

PMID- 9910062
TI  - Two theorems for the group velocity in dispersive media.

PMID- 9910061
TI  - Free and dissipative evolution of squeezed and displaced number states in the
      third-order nonlinear oscillator.

PMID- 9910064
TI  - Intrinsic decoherence in the atom-field interaction.

PMID- 9910063
TI  - Amplitude squeezing and a transition from lasing with inversion to lasing without
      inversion in a four-level laser.

PMID- 9910066
TI  - Probe absorption spectrum of a laser-driven atom near a phase conjugator.

PMID- 9910065
TI  - High-order harmonic radiation from solid layers irradiated by subpicosecond laser
      pulses.

PMID- 9910067
TI  - Soliton dynamics, anti-Stokes generation, and diffraction in stimulated Raman
      scattering.

PMID- 9910069
TI  - Statistics of nonclassical lasers generated via pump-noise suppression.

PMID- 9910068
TI  - Surface-state hydrogen maser.

PMID- 9910070
TI  - Frequency conversion and amplification of photon-number detection.

PMID- 9910071
TI  - Analytic solution for quasiprobability distributions of the Jaynes-Cummings model
      with cavity damping.

PMID- 9910072
TI  - Single-atom fluorescence with nonclassical light.

PMID- 9910074
TI  - Further tests of a scaled local exchange-correlation functional.

PMID- 9910073
TI  - Observation of the negative ions: Ra-, Pa-, and Pu-

PMID- 9910076
TI  - Preparation of high-principal-quantum-number "circular" states of rubidium.

PMID- 9910075
TI  - Scattering on two solenoids.

PMID- 9910077
TI  - High-frequency stabilization and high-order harmonic generation of an excited
      Morse oscillator under intense fields.

PMID- 9910078
TI  - Comment on "Einstein-Podolsky-Rosen state for space-time variables in a two
      photon interference experiment"

PMID- 9910079
TI  - Reply to "Comment on 'Einstein-Podolsky-Rosen state for space-time variables in a
      two-photon interference experiment' "

PMID- 9910080
TI  - Erratum: Berry's phase for anharmonic oscillators

PMID- 9910081
TI  - Quantum-algebraic description of quantum superintegrable systems in two
      dimensions.

PMID- 9910082
TI  - Electron transfer in Ca*(4snl)-Ca(4s2) collisions.

PMID- 9910083
TI  - Ellipsoidal angular distribution of electrons emitted from Rydberg atoms.

PMID- 9910084
TI  - Stochastic path-integral simulation of quantum scattering.

PMID- 9910085
TI  - Elusive C 3 Pi u state lifetime of molecular nitrogen.

PMID- 9910086
TI  - Quantum calculations for one-dimensional laser cooling: Temporal evolution.

PMID- 9910087
TI  - Cold-collision properties derived from frequency shifts in a cesium fountain.

PMID- 9910089
TI  - Influence of ellipticity on harmonic generation.

PMID- 9910088
TI  - High-order Harmonic-generation cutoff.

PMID- 9910091
TI  - Effect of rotations on stabilization in high-intensity photodissociation of H2+

PMID- 9910090
TI  - Electron energy distribution in the photodetachment of H- by two radiation
      fields.

PMID- 9910092
TI  - Vibrational dependence of negative-ion formation by dissociative attachment of
      low-energy electrons.

PMID- 9910094
TI  - Reflection beam splitter for multilevel atoms.

PMID- 9910093
TI  - Competition between atomic and molecular Auger decays: Study of the resonant
      Auger decay of HBr after the Br 3d--> sigma * transition.

PMID- 9910095
TI  - Possibility of breakdown of atomic stabilization in an intense high-frequency
      field.

PMID- 9910096
TI  - Nonlinear effects of radiation trapping in ground-state oriented sodium vapor.

PMID- 9910097
TI  - Continuous polarization-gradient precooling-assisted velocity-selective coherent
      population trapping.

PMID- 9910098
TI  - Necessity of sine-cosine joint measurement.

PMID- 9910099
TI  - Interplay of linear and nonlinear effects in the formation of optical vortices in
      a nonlinear resonator.

PMID- 9910100
TI  - Radial squeezed states and Rydberg wave packets.

PMID- 9910101
TI  - High-order harmonic emission from mixed fields.

PMID- 9910102
TI  - Lasing without inversion: Gain enhancement through spectrally colored population
      pumping.

PMID- 9910103
TI  - Multiphoton dissociation for coherent and incoherent fields.

PMID- 9910104
TI  - Quantum-statistical properties of a particle in a double-harmonic-oscillator
      potential: Generation of Schrodinger-cat states.

PMID- 9910105
TI  - Canonical quantization of four- and five-dimensional U(1) gauge theories.

PMID- 9910106
TI  - Path-integral Monte Carlo method in quantum statistics for a system of N
      identical fermions.

PMID- 9910107
TI  - Measurements, errors, and negative kinetic energy.

PMID- 9910108
TI  - Energy and beta -function solutions to relativistic Hamiltonians with Coulombic
      and linear potentials.

PMID- 9910110
TI  - Quantized geometry associated with uncertainty and correlation.

PMID- 9910109
TI  - Functional representations in non-Fourier basis with applications.

PMID- 9910112
TI  - Large-scale multiconfiguration Hartree-Fock calculations of hyperfine-interaction
      constants for low-lying states in beryllium, boron, and carbon.

PMID- 9910111
TI  - Anapole moments of atoms.

PMID- 9910113
TI  - Weak and nucleoweak decays of muonic molecules.

PMID- 9910114
TI  - Muonic-molecule formation in a high-density D-T system: Application to a solid
      phase.

PMID- 9910116
TI  - Upper and lower bounds on the radial electron density in atoms.

PMID- 9910115
TI  - Radiative lifetimes of triply excited states of the Li isoelectronic sequence.

PMID- 9910117
TI  - Application of unitary-group methods to composite systems.

PMID- 9910119
TI  - Riccati-Pade quantization and oscillators V(r)=gr alpha.

PMID- 9910118
TI  - Preconvolving theoretical photoabsorption cross sections using multichannel
      quantum-defect theory.

PMID- 9910121
TI  - Classical mechanics of two-electron atoms.

PMID- 9910122
TI  - Weighted-density exchange and local-density Coulomb correlation energy
      functionals for finite systems: Application to atoms.

PMID- 9910120
TI  - Hydrogen atom in a high magnetic field.

PMID- 9910124
TI  - Retarded Casimir interaction in the asymptotic domain of an electron and a
      dielectric wall.

PMID- 9910123
TI  - Elementary approximate derivations of some retarded Casimir interactions
      involving one or two dielectric walls.

PMID- 9910125
TI  - Retarded electric and magnetic Casimir interaction of a polarizable system and a
      dielectric permeable wall.

PMID- 9910126
TI  - Fast inelastic ion-ion, ion-electron, and ion-positron collisions.

PMID- 9910127
TI  - Intermediate-velocity atomic collisions. VI. Screening, antiscreening, and
      related processes in He++( H2, He).

PMID- 9910128
TI  - Results from the nonrelativistic dipole-approximation theory of two-photon
      electron bremsstrahlung in the Coulomb field.

PMID- 9910129
TI  - Path-integral approach to resonant electron-molecule scattering. II. Second-order
      cumulant approximation and multimode applications.

PMID- 9910130
TI  - Electron-impact ionization of In+ and Xe+

PMID- 9910131
TI  - Electron-impact excitation of the n=3 and n=2 states of a hydrogen atom at
      intermediate (14-100-eV) energies.

PMID- 9910132
TI  - Theoretical investigations of charge exchange with ion excitation in atomic
      collisions at thermal energies.

PMID- 9910134
TI  - Test of local model potentials for positron scattering from rare gases.

PMID- 9910133
TI  - Laser-induced-resonance calculations for the photodissociation of H2+ in an
      adiabatic electronic-field representation using the radiation-field gauge.

PMID- 9910135
TI  - Quantal and classical differential-scattering calculations for the electron
      impact excitation of argon ions.

PMID- 9910137
TI  - Temperature dependence of He(2 (3)PJ) reactions: Collision-induced mixing and
      conversion to He2( 3 Pi g) molecules.

PMID- 9910136
TI  - Ne ionization induced by the impact of 106-keV/u H+ and 3He2+: Two-center effects
      on the soft-electron emission.

PMID- 9910138
TI  - Extreme-ultraviolet absorption spectrum of Ga+

PMID- 9910139
TI  - Energy approach to consistent QED theory for calculation of electron-collision
      strengths: Ne-like ions.

PMID- 9910140
TI  - Single-, double-, and triple-photoionization cross sections of carbon monoxide
      (CO) and ionic fragmentation of CO+, CO2+, and CO3+

PMID- 9910142
TI  - Population of high-L sulfur Rydberg levels by ion-Rydberg-atom charge exchange.

PMID- 9910141
TI  - Satellite structure of the neon valence shell by electron-momentum spectroscopy.

PMID- 9910143
TI  - Solid-state effects on Rayleigh-scattering experiments: Limits for the free-atom
      approximation.

PMID- 9910144
TI  - Gaseous 3He-3He magnetic dipolar spin relaxation.

PMID- 9910145
TI  - Charge-state dependence of binary-encounter-electron cross sections and peak
      energies.

PMID- 9910146
TI  - Photoionization of the scandium atom. I. General features.

PMID- 9910147
TI  - Photoionization of the scandium atom. II. Classifications.

PMID- 9910148
TI  - Photoionization of the scandium atom. III. Experimental and theoretical spectra
      from an excited state.

PMID- 9910150
TI  - Energy loss of hydrogen projectiles in gases.

PMID- 9910149
TI  - DD nuclear-fusion reactions with small D2O and H2O clusters impacting heavy ice.

PMID- 9910151
TI  - Above-surface neutralization of slow N6+ ions during interactions with a Cu(001)
      target.

PMID- 9910152
TI  - Work-function dependence of above-surface neutralization of multicharged ions.

PMID- 9910153
TI  - Relationship between effective-Hamiltonian and effective-Liouvillian dynamics.

PMID- 9910155
TI  - Experimental and theoretical study of the hyperfine structure in the 4f75d6s6p
      configuration of Gd I.

PMID- 9910154
TI  - Stark mapping of H2 Rydberg states in the strong-field regime with dynamical
      resolution.

PMID- 9910156
TI  - Distortion of atomic states by time-dependent electric fields.

PMID- 9910157
TI  - Three-dimensional hydrogen atom in crossed magnetic and electric fields.

PMID- 9910158
TI  - Semiclassical Floquet theory of the S matrix for electromagnetic interactions.

PMID- 9910160
TI  - Observation of dynamic suppression of spontaneous emission in a strongly driven
      cavity.

PMID- 9910159
TI  - Ponderomotive potential and dynamical Stark shift in multiphoton ionization.

PMID- 9910161
TI  - Intense-field renormalization of cavity-induced spontaneous emission.

PMID- 9910162
TI  - Parametric oscillator pumped by a quantum current.

PMID- 9910163
TI  - High-order harmonic generation in laser-produced ions.

PMID- 9910164
TI  - Stabilization of transverse solitary waves by a nonlocal response of the
      nonlinear medium.

PMID- 9910165
TI  - Effects of the laser parameters on the determination of the Sn isotope ratio.

PMID- 9910166
TI  - Analytical approach to the photon statistics in the thermal Jaynes-Cummings model
      with an initially unexcited atom.

PMID- 9910168
TI  - Transverse patterns in nascent optical bistability.

PMID- 9910167
TI  - Realistic optical homodyne measurements and quasiprobability distributions.

PMID- 9910169
TI  - Nonlocal interferometry with high-intensity fields.

PMID- 9910170
TI  - Many-port homodyne detection of an optical phase.

PMID- 9910172
TI  - Gain in a three-level Lambda system driven by a single pump.

PMID- 9910171
TI  - Detection of quantum noise.

PMID- 9910173
TI  - Generation of pure states in a two-photon micromaser: Effects of finite detuning
      and cavity losses.

PMID- 9910174
TI  - Multiphoton detachment of H-

PMID- 9910175
TI  - One-dimensional model of a negative ion and its interaction with laser fields.

PMID- 9910177
TI  - Effect of atomic coherence on the second- and higher-order squeezing in a two
      photon three-level cascade atomic system.

PMID- 9910176
TI  - Prepulse technique for producing low-Z Ne-like x-ray lasers.

PMID- 9910179
TI  - Phase-difference operator.

PMID- 9910178
TI  - Marginal distributions of quasiprobabilities in quantum optics.

PMID- 9910180
TI  - High-order harmonic generation in rare gases with an intense short-pulse laser.

PMID- 9910181
TI  - Femtosecond pulses in the focal region of lenses.

PMID- 9910182
TI  - Degree of visibility in experiments of induced coherence without induced
      emission: A heuristic approach.

PMID- 9910184
TI  - Microwave multiphoton Rabi oscillations.

PMID- 9910183
TI  - Quantum-statistical properties of a Raman-type model.

PMID- 9910185
TI  - Light-beam propagation at planar thin-film nonlinear waveguides.

PMID- 9910186
TI  - Remark on the propagator of the radial oscillator.

PMID- 9910187
TI  - Casimir-Polder potential as an interaction between induced dipoles.

PMID- 9910189
TI  - Momentum unimodality effects in atomic systems.

PMID- 9910188
TI  - Recurrence relations for N-dimensional radial wave functions.

PMID- 9910190
TI  - Perturbation effects on lifetimes of d 3 Pi u states in H2 and D2.

PMID- 9910191
TI  - Roothaan-Hartree-Fock wave functions for atoms from Cs through U.

PMID- 9910192
TI  - Completely local relativistic density-functional theory: The role of the virial.

PMID- 9910193
TI  - Variational calculation of ground-state energy of positronium negative ions.

PMID- 9910194
TI  - Model calculations of multielectron ionization of O2 molecules by fast-heavy-ion
      impact.

PMID- 9910195
TI  - Convergent close-coupling calculations of low-energy positron-atomic-hydrogen
      scattering.

PMID- 9910196
TI  - Assessing the entropy changes of Bloch-vector trajectories using experimental
      data.

PMID- 9910197
TI  - Interference and indistinguishability governed by time delays in a low-Q cavity.

PMID- 9910198
TI  - Quantum interferences in the collisional excitation of a structured continuum.

PMID- 9910199
TI  - Comment on "Elastic scattering of hydrogen atoms at low temperatures"

PMID- 9910200
TI  - Erratum: Scattering of positrons by hydrogen in a modified Glauber method

PMID- 9910201
TI  - Erratum: Energy corrections of order mc2 alpha 6 ln alpha in helium

PMID- 9910202
TI  - Tunneling dynamics of squeezed states in a potential well.

PMID- 9910203
TI  - Noise-dependent uncertainty relations for the harmonic oscillator.

PMID- 9910205
TI  - General linear transformations and entangled states.

PMID- 9910204
TI  - Level-spacing distribution of the harmonic oscillator.

PMID- 9910207
TI  - Some limits to precision phase measurement.

PMID- 9910206
TI  - Three proposed "quantum erasers"

PMID- 9910209
TI  - Relativistic Coulomb wave functions in momentum space.

PMID- 9910208
TI  - Density-functional theory as an example for the construction of stationarity
      principles.

PMID- 9910210
TI  - Evolution of coherences and populations in the secular approximation.

PMID- 9910211
TI  - Collision operator for isolated ion lines in the standard Stark-broadening theory
      with applications to the Z scaling in the Li isoelectronic series 3P-3S
      transition.

PMID- 9910212
TI  - Isotope shift in the tantalum atomic spectrum.

PMID- 9910214
TI  - Muonic-hydrogen molecular bound states, quasibound states, and resonances in the
      Born-Oppenheimer approximation.

PMID- 9910213
TI  - Determination of radiative lifetimes in the 3d10np 2P sequence of neutral copper
      by time-resolved vuv laser spectroscopy.

PMID- 9910215
TI  - Self-broadening and exciton line shifts in gases: Beyond the local-field
      approximation.

PMID- 9910216
TI  - Observations of doubly excited states in lithiumlike calcium.

PMID- 9910217
TI  - High-resolution photoabsorption near the sulfur L2,3 thresholds: H2S and D2S.

PMID- 9910218
TI  - Hartree-Fock study of molecules in very intense magnetic fields.

PMID- 9910220
TI  - Relativistic corrections to the Zeeman effect in hydrogenlike atoms and
      positronium.

PMID- 9910219
TI  - Two-electron atoms: o(4,2) operator replacements and large-order perturbation
      theory with respect to the replaced kinetic-energy operator.

PMID- 9910221
TI  - Lamb shifts and hyperfine structure in 6Li+ and 7Li+: Theory and experiment.

PMID- 9910222
TI  - Investigation of LS coupling in boronlike ions.

PMID- 9910223
TI  - Determination of mean energies and impact parameters characteristic of charge
      changing reactions.

PMID- 9910224
TI  - Radiative interference effects in the dielectronic-recombination process of an
      electron with hydrogenlike uranium.

PMID- 9910225
TI  - Near-threshold photoionization spectrum of aligned Ca 4s5p 1P1.

PMID- 9910226
TI  - Excitation functions of He(n=3) levels in the intermediate-velocity regime of He+
      He collisions.

PMID- 9910227
TI  - Electron detachment in low-energy collisions of halogen anions with atomic
      hydrogen.

PMID- 9910228
TI  - Exact analytical solution of the quantum Rosen-Zener-Demkov model.

PMID- 9910229
TI  - Ab initio treatment of electron capture by B4+ ions from atomic hydrogen.

PMID- 9910230
TI  - High-resolution monochromatized He II alpha -excited photoelectron spectrum of Ar
      between 28 and 40.8 eV.

PMID- 9910231
TI  - Angular distribution of ions axially channeled in a very thin crystal:
      Experimental and theoretical results.

PMID- 9910232
TI  - Inner-shell photoionization of group-IIB atoms.

PMID- 9910234
TI  - Ionization and dissociation of N2 and CO in collisions with 2.3q-keV Arq+ (8 <= q
      <= 14).

PMID- 9910233
TI  - Inner-shell capture using atomic potentials: A distorted strong-potential Born
      treatment.

PMID- 9910236
TI  - Ionization of muonic atoms by nonrelativistic electrons.

PMID- 9910235
TI  - L-shell ionization studies of Pb and Bi with alpha particles.

PMID- 9910237
TI  - Relation between the electron scattering length and the van der Waals
      approximation to the equation of state.

PMID- 9910239
TI  - Measurement of C3+ dielectronic recombination in a known external field.

PMID- 9910238
TI  - Systematics and scaling of differential ionization cross sections in multicharged
      ion-atom collisions.

PMID- 9910240
TI  - State-selective charge transfer between He-like ions and He.

PMID- 9910241
TI  - Radiative electron capture by fully stripped channeled light ions.

PMID- 9910242
TI  - Photon-echo interferometry to measure collision-induced optical phase shifts.

PMID- 9910243
TI  - Dependence of electron-capture probabilities on the initial-state magnetic
      quantum numbers in ion-atom collisions.

PMID- 9910244
TI  - Laser cooling and quantum jumps of a single indium ion.

PMID- 9910245
TI  - Frequency evolution of radiatively assisted collisions of K Rydberg atoms.

PMID- 9910247
TI  - Effective Hamiltonian for the radiation in a cavity with a moving mirror and a
      time-varying dielectric medium.

PMID- 9910246
TI  - Laser cooling of trapped ions: The influence of micromotion.

PMID- 9910248
TI  - Effect of finite bandwidth on refractive-index enhancement and lasing without
      inversion.

PMID- 9910249
TI  - Effects of finite bandwidth on the resonance fluorescence spectrum inside of a
      cavity.

PMID- 9910250
TI  - Field-correlation effects in two-photon absorption from randomly amplitude
      modulated laser fields.

PMID- 9910251
TI  - State evolution in the two-photon atom-field interaction with large initial
      fields.

PMID- 9910252
TI  - Quantum-statistical properties of noise in a phase-sensitive linear amplifier.

PMID- 9910253
TI  - Short-wavelength soft-x-ray amplification in a lithiumlike calcium plasma.

PMID- 9910254
TI  - Generation of mixtures of Schrodinger-cat states from a competitive two-photon
      process.

PMID- 9910255
TI  - Extra intracavity squeezing of a degenerate optical parametric oscillator
      coupling with N two-level atoms.

PMID- 9910256
TI  - First-order-like transition for colored saturation models of dye lasers: Effects
      of quantum noise.

PMID- 9910257
TI  - Sum- and difference-frequency generation for broadband input fields.

PMID- 9910258
TI  - Measurement of phase differences between two partially coherent fields.

PMID- 9910259
TI  - Generation and detection of nonclassical field states by conditional measurements
      following two-photon resonant interactions.

PMID- 9910260
TI  - High-order harmonic generation in rare gases with subpicosecond XeCl laser
      pulses.

PMID- 9910261
TI  - Quantum theory of correlated-atomic-position measurements by resonance imaging.

PMID- 9910263
TI  - Nonlinear Schrodinger equation for optical media with quadratic nonlinearity.

PMID- 9910262
TI  - Significance of Rontgen current in quantum optics: Spontaneous emission of moving
      atoms.

PMID- 9910265
TI  - Induced transitions and energy of a damped oscillator.

PMID- 9910264
TI  - Exact solution of the two-dimensional Dirac oscillator.

PMID- 9910266
TI  - Evolution of the wave function in a dissipative system.

PMID- 9910267
TI  - Partial widths with interchannel coupling to all orders for the H- two-electron
      ionization ladder of 1D symmetry.

PMID- 9910268
TI  - Modified shifted-large-N approach to an exponential potential.

PMID- 9910269
TI  - Electron-capture contribution to the stopping power of low-energy hydrogen beams
      passing through helium.

PMID- 9910270
TI  - Accuracy of molecular data in the understanding of ultracold collisions.

PMID- 9910271
TI  - Improved fitting of a vibrorotation model to the dynamics of a modulated CO2
      laser.

PMID- 9910272
TI  - Anomalous conical emission: Two-beam experiments.

PMID- 9910273
TI  - Evolution of wave functions in the two-photon Jaynes-Cummings model: The
      generation of superpositions of coherent states.

PMID- 9910275
TI  - Phase properties of a field mode interacting with N two-level atoms.

PMID- 9910274
TI  - Tunable x-ray laser.

PMID- 9910276
TI  - Observation of a nonlocal Pancharatnam phase shift in the process of induced
      coherence without induced emission.

PMID- 9910278
TI  - Convergent close-coupling calculation of electron-sodium scattering.

PMID- 9910277
TI  - Erratum: Photoabsorption of atoms inside C60

PMID- 9910279
TI  - Positron-atom doubly differential ionization cross sections.

PMID- 9910280
TI  - Isotope separation using intense laser fields.

PMID- 9910281
TI  - Ionization of helium by a short pulse of radiation: A Fermi molecular-dynamics
      calculation.

PMID- 9910282
TI  - Observation of velocity-tuned resonances in the reflection of atoms from an
      evanescent light grating.

PMID- 9910283
TI  - Possibility of producing the one-photon state in a kicked cavity with a nonlinear
      Kerr medium.

PMID- 9910285
TI  - Angularly resolved high-order harmonic generation in helium.

PMID- 9910284
TI  - Observation and characterization of deterministic chaos in stimulated Brillouin
      scattering with weak feedback.

PMID- 9910286
TI  - Lower bound for accessible information in quantum mechanics.

PMID- 9910287
TI  - Inertia as a zero-point-field Lorentz force.

PMID- 9910288
TI  - Calculation of the Landau quasiclassical exponent from the Fourier components of
      classical functions.

PMID- 9910290
TI  - Analogies between light and electrons: Density of states and Friedel's identity.

PMID- 9910289
TI  - Eigenvectors of two particles' relative position and total momentum.

PMID- 9910291
TI  - Supersymmetric quaternionic quantum mechanics.

PMID- 9910292
TI  - Temperature-induced transition rates for some hydrogenic states.

PMID- 9910293
TI  - Nonconvexity of the atomic charge density and shell structure.

PMID- 9910295
TI  - Vibrational and rotational structure in the He I-excited photoelectron spectrum
      of the A 2 Sigma 1/2+ state of HBr+

PMID- 9910294
TI  - Line-shape effects on the determination of Coster-Kronig probabilities using
      Si(Li) x-ray detectors.

PMID- 9910296
TI  - Measurement and interpretation of the odd-parity levels of Pb I.

PMID- 9910297
TI  - Even-parity autoionizing states in the extreme-ultraviolet photoabsorption
      spectra of Mg, Al+, and Si2+

PMID- 9910299
TI  - Angular correlation of K-L x-ray cascades in gadolinium.

PMID- 9910298
TI  - Isotope shift and hyperfine structure in Lu I and W I.

PMID- 9910300
TI  - D1(5 (1)P1)X0(+)(5 (1)S0) spectra of CdNe and CdAr excited in crossed molecular
      and laser beams.

PMID- 9910301
TI  - Theoretical treatment of radiation trapping: Steady-state conditions and
      quenching experiment.

PMID- 9910302
TI  - Single-Fock-operator method for matrix Dirac-Fock self-consistent-field
      calculations on open-shell atoms.

PMID- 9910303
TI  - Counting the number of vibrational states of a molecule to improve the Born
      Oppenheimer estimate.

PMID- 9910304
TI  - Isotope shift in the neon ground state by extreme-ultraviolet laser spectroscopy
      at 74 nm.

PMID- 9910306
TI  - Coplanar structures in L=0 even-parity intrashell states of four-valence-electron
      atoms.

PMID- 9910305
TI  - Force field and potential due to the Fermi-Coulomb hole charge for nonspherical
      density atoms.

PMID- 9910307
TI  - Transverse exchange energy in relativistic density-functional calculations: An
      alternative approximation.

PMID- 9910308
TI  - Dynamic scalar and tensor polarizabilities of the 2 (1)P and 2 (3)P states of He.

PMID- 9910309
TI  - Hyperspherical functions with arbitrary permutational symmetry.

PMID- 9910311
TI  - Resonances and recurrences in the absorption spectrum of an atom in an electric
      field.

PMID- 9910310
TI  - Recurrence spectroscopy: Observation and interpretation of large-scale structure
      in the absorption spectra of atoms in magnetic fields.

PMID- 9910312
TI  - Velocity dependence of ionization and fragmentation of methane caused by fast
      proton impact.

PMID- 9910314
TI  - Theoretical studies of the K-shell Auger spectrum of atomic oxygen.

PMID- 9910313
TI  - Rayleigh scattering from crystals and amorphous structures.

PMID- 9910315
TI  - Spin-polarization parameters and cross sections for electron scattering from zinc
      and lead atoms.

PMID- 9910316
TI  - Resonant collisions of K Rydberg atoms.

PMID- 9910318
TI  - Resonant collisional dissociation of Na2+ by Na(3p) in an effusive beam.

PMID- 9910317
TI  - t matrix in hard-core two-body scattering in three and two dimensions.

PMID- 9910319
TI  - Production of electronically excited N2+ ions by electron impact on N2 molecules.

PMID- 9910320
TI  - Dielectronic capture processes in the electron-impact ionization of Sc2+

PMID- 9910322
TI  - Transferred orbital angular momentum in the excitation of 138Ba(.6s6p 6 (1)P1) by
      electron impact.

PMID- 9910321
TI  - Many-body calculation of photoionization cross sections in CO.

PMID- 9910324
TI  - Charge transfer of H+ with Cl and Cl+ with H.

PMID- 9910323
TI  - Resonance structure in the 2p photoionization of atomic sodium close to the 2s
      threshold.

PMID- 9910325
TI  - Small-angle elastic scattering of high-energy electrons by H2, HD, and D2.

PMID- 9910326
TI  - Multichannel-quantum-defect-theory analysis of the Stark effect in autoionizing
      Rydberg states of H2.

PMID- 9910327
TI  - Dispersion coefficients for alkali-metal dimers.

PMID- 9910329
TI  - Relationship between a nonlinear response and relaxation induced by colored
      noise.

PMID- 9910328
TI  - Electron-impact-ionization cross section for the hydrogen atom.

PMID- 9910330
TI  - Single and double K-shell ionization and electron-transfer cross sections for Fe
      and Ni bombarded by S ions and Fe by Si ions at 1.25-4.70 MeV/amu.

PMID- 9910332
TI  - Asymmetric two-electron excitations in atomic strontium and barium.

PMID- 9910331
TI  - Critical study of photodetachment of H- at energies up to the n=4 threshold.

PMID- 9910334
TI  - Wave functions for continuum states of charged fragments.

PMID- 9910333
TI  - Elastic scattering of electrons from Xe, Cs+, and Ba2+

PMID- 9910335
TI  - Photoionization from metastable (1s2s) 1Se and 3Se states of the He atom for
      energies between the N=2 and 3 thresholds of He+

PMID- 9910336
TI  - Convergent close-coupling method for the calculation of electron scattering on
      hydrogenlike targets.

PMID- 9910337
TI  - Energy loss of slow protons in solids: Deviation from the proportionality with
      projectile velocity.

PMID- 9910338
TI  - Partial stopping power and straggling effective charges of heavy ions in
      condensed matter.

PMID- 9910339
TI  - Numerical study of the multiple-scattering series for gas-solid dynamics
      including single- through triple-collision terms.

PMID- 9910340
TI  - Charge-state distributions of scattered and recoil ions in C+-, F+-, and Ne+-Si
      surface collisions.

PMID- 9910341
TI  - Role of the surface in the electronic effective mass of metal microclusters.

PMID- 9910342
TI  - Laser cooling of a sodium atomic beam using the Stark effect.

PMID- 9910344
TI  - Keldysh-like expansion for above-threshold ionization.

PMID- 9910343
TI  - Effect of virtual Compton scattering on electron propagation in a laser field.

PMID- 9910345
TI  - Kinetic effects of 3-13-photon velocity-tuned resonances investigated by a time
      of-flight technique.

PMID- 9910347
TI  - Laser isotope separation of barium using an inhomogeneous magnetic field.

PMID- 9910346
TI  - Dynamic and steady-state behaviors of reverse saturable absorption in
      metallophthalocyanine.

PMID- 9910348
TI  - Suppression of resonant multiphoton ionization via Rydberg states.

PMID- 9910349
TI  - Alternating kicks approximating quasimonochromatic fields in ionization and
      stabilization.

PMID- 9910350
TI  - Laser-induced forces near a metallic surface.

PMID- 9910351
TI  - Spectral widths of H2+ multiphoton dissociation with short intense laser pulses.

PMID- 9910352
TI  - Multielectron stabilization of atoms in a laser field: Classical perspective.

PMID- 9910354
TI  - Multiphoton detachment, ionization, and simultaneous excitation of two-electron
      systems.

PMID- 9910353
TI  - Quantum collapse and revival in the motion of a single trapped ion.

PMID- 9910355
TI  - From sub-Poissonian to super-Poissonian pumping in the micromaser: Corrections to
      reservoir theory.

PMID- 9910356
TI  - Quantum statistics of a two-mode SU(1,1) interferometer.

PMID- 9910358
TI  - Determination of weak decay rates by monitoring coupled strong transitions.

PMID- 9910357
TI  - Stability properties of a resonant cascade laser.

PMID- 9910359
TI  - Comparison of quantum-state diffusion and quantum-jump simulations of two-photon
      processes in a dissipative environment.

PMID- 9910360
TI  - Superdressed two-level atom: Very high harmonic generation and multiresonances.

PMID- 9910361
TI  - Complete basis set via straight-line coherent-state superpositions.

PMID- 9910363
TI  - Uniqueness of the chaotic attractor of a single-mode laser.

PMID- 9910362
TI  - Effect of the pump state on the behavior of the degenerate parametric amplifier.

PMID- 9910364
TI  - Bifurcation to standing and traveling waves in large arrays of coupled lasers.

PMID- 9910365
TI  - Method of integral equations and an extinction theorem in bulk and surface
      phenomena in nonlinear optics.

PMID- 9910366
TI  - Third-order nonlinear optical response resulting from optical pumping: Effects of
      atomic motion.

PMID- 9910367
TI  - Quantum-noise reduction using a cavity with a movable mirror.

PMID- 9910368
TI  - Bifurcation in a cw-pumped Brillouin fiber-ring laser: Coherent soliton
      morphogenesis.

PMID- 9910369
TI  - Squeezing via feedback.

PMID- 9910371
TI  - Radiative properties of a two-level system in the presence of mirrors.

PMID- 9910370
TI  - Two-mode micromaser operating on three-level atoms.

PMID- 9910373
TI  - Geometric phases in lasers and liquid flows.

PMID- 9910372
TI  - Phase-space representation of operational phase operators.

PMID- 9910374
TI  - Quantum noise and squeezing in an optical parametric oscillator with arbitrary
      output-mirror coupling. II. Extension to double-sided cavities.

PMID- 9910375
TI  - Quantum noise and squeezing in an optical parametric oscillator with arbitrary
      output-mirror coupling. III. Effect of pump amplitude and phase fluctuations.

PMID- 9910376
TI  - Dynamical transverse laser patterns. I. Theory.

PMID- 9910377
TI  - Dynamical transverse laser patterns. II. Experiments.

PMID- 9910378
TI  - Electric charges of positive and negative muons.

PMID- 9910379
TI  - Magnetic moment of the negative muon.

PMID- 9910380
TI  - Teleportation of quantum states.

PMID- 9910381
TI  - Ground-state energy of singular potentials.

PMID- 9910383
TI  - Dissociation cross sections of ionic hydrogen clusters by collisions with helium
      at 60 keV/amu.

PMID- 9910382
TI  - Auger hypersatellites in Ne atoms induced by electron impact.

PMID- 9910384
TI  - Polarization-sensitive population trapping in an optically pumped laser.

PMID- 9910385
TI  - Spatial anisotropy of the velocity of electrons emitted from a short-pulse laser
      focus.

PMID- 9910386
TI  - Double-well dynamics of two ions in the Paul and Penning traps.

PMID- 9910387
TI  - Phase-dependent amplification in pump-probe experiments.

PMID- 9910388
TI  - Isotope effects and bond softening in intense-laser-field multiphoton
      dissociation of H2+

PMID- 9910389
TI  - Atomic probe for quantum states of the electromagnetic field.

PMID- 9910390
TI  - Phase, coherence properties, and the numerical analysis of the field in the
      nonresonant Jaynes-Cummings model.

PMID- 9910391
TI  - Erratum: Ionization in positron-atom collisions

PMID- 9910392
TI  - Erratum: Quenching of low-lying Rydberg states of Na colliding with ground-state
      He: A semiclassical approach

PMID- 9910394
TI  - Localization of two-level systems.

PMID- 9910393
TI  - Pseudo-master-equation for the no-count process in a continuous photodetection.

PMID- 9910395
TI  - Fragment angular distribution in one- and two-color photodissociation by strong
      laser fields.

PMID- 9910397
TI  - Verification of the ponderomotive approximation for the ac Stark shift in Xe
      Rydberg levels.

PMID- 9910396
TI  - Ionization of hydrogen atoms by multiply charged ions at low energies: The
      scaling law.

PMID- 9910398
TI  - Observation of strong electronic correlation for highly excited double Rydberg
      states of ytterbium.

PMID- 9910399
TI  - Nonlinear resonances and the melting of Wigner crystals in a Paul trap.

PMID- 9910400
TI  - Symmetry-breaking effects induced by intense laser fields.

PMID- 9910402
TI  - Feynman's approach to negative probability in quantum mechanics.

PMID- 9910401
TI  - Scheme to measure the positive P distribution.

PMID- 9910403
TI  - Quantum-noise matrix for multimode systems: U(n) invariance, squeezing, and
      normal forms.

PMID- 9910404
TI  - Electromagnetic electron-positron pair production in heavy-ion collisions with
      impact parameter zero.

PMID- 9910405
TI  - Relation between the moment of inertia and moments of density.

PMID- 9910407
TI  - Why quantum mechanics cannot be formulated as a Markov process.

PMID- 9910406
TI  - Composition law of amplitudes and quantum theory.

PMID- 9910408
TI  - Inequivalence between the Schrodinger equation and the Madelung hydrodynamic
      equations.

PMID- 9910409
TI  - Effect of interchannel coupling on the partial and total autoionization widths:
      Application to the 1s3s3p 4Po and 1s3p2 4P states for Z=2-5, 10.

PMID- 9910410
TI  - Stationary multideterminantal coupled-cluster response.

PMID- 9910411
TI  - Dynamics of confined ions driven by light beams: A singular perturbation
      approach.

PMID- 9910412
TI  - Evaluation of some integrals for the atomic three-electron problem using
      convergence accelerators.

PMID- 9910414
TI  - Measurement of the cross sections for collisional broadening of the
      intercombination transitions in calcium and strontium.

PMID- 9910413
TI  - Ionization energy of rubidium Rydberg atoms in strong crossed electric and
      magnetic fields.

PMID- 9910416
TI  - Bound P states (L=1) and D states (L=2) of three-body muonic molecular ions.

PMID- 9910415
TI  - Absolute term energy of core-excited doublet states of lithium.

PMID- 9910417
TI  - Approximate sum rule for diatomic vibronic states.

PMID- 9910418
TI  - Calculation of C6 dispersion constants with coupled-cluster theory.

PMID- 9910419
TI  - Time dependence of physical observables in wave-packet states.

PMID- 9910420
TI  - Hydrogen molecule under confinement: Exact results.

PMID- 9910421
TI  - Correlated two-electron wave functions of any symmetry.

PMID- 9910422
TI  - Open-shell relativistic coupled-cluster method with Dirac-Fock-Breit wave
      functions: Energies of the gold atom and its cation.

PMID- 9910423
TI  - Sixfold differential cross sections for atomic helium, magnesium, and calcium in
      ( gamma,2e) experiments.

PMID- 9910424
TI  - Laser-assisted scattering from a one-dimensional delta -function potential: An
      exact solution.

PMID- 9910426
TI  - Rovibrational excitation in collisions of He on D2 at energies less than 2 keV.

PMID- 9910425
TI  - Calculation of the cross sections for positron- and proton-impact ionization of
      helium.

PMID- 9910427
TI  - Coupled-state differential cross sections for electron transfer and elastic
      scattering in collisions between protons and He+ ions.

PMID- 9910428
TI  - Mean lifetime of the bound 2p sigma state of HeH2+

PMID- 9910429
TI  - Effects of Coster-Kronig transitions on electron-impact excitation rates for
      fluorinelike ions in their ground states.

PMID- 9910430
TI  - 15-state R-matrix investigation of resonances in the inelastic scattering of
      electrons from atomic hydrogen at energies up to 13.06 eV.

PMID- 9910431
TI  - Coster-Kronig decay of 3p core-excited states of atomic zinc.

PMID- 9910432
TI  - Electron capture in collisions of excited Na*(3p) atoms with He+ ions at 0.1-7
      keV/u: Effects of alignment of the initial Na*(3p) orbital.

PMID- 9910433
TI  - Unified treatment of electron-ion recombination in the close-coupling
      approximation.

PMID- 9910434
TI  - Nonadiabatic effects on resonance-enhanced two-photon dissociation of H2.

PMID- 9910435
TI  - Radiative electron capture by high-energy oxygen ions in hydrogen and helium.

PMID- 9910436
TI  - Differential cross sections and angular-correlation parameters for the excitation
      of hydrogen atoms to n=3 and n=2 states by electron impact between 16 and 100 eV.

PMID- 9910437
TI  - Simplest doubly charged negative ion: Nonexistence of H2- resonances.

PMID- 9910439
TI  - Dynamical image potential and induced forces for charged particles moving
      parallel to a solid surface.

PMID- 9910438
TI  - Radiative electron capture in relativistic atomic collisions.

PMID- 9910440
TI  - Interplay of charge exchange and energy loss of 0.67-1.5-MeV He ions specularly
      reflected from a crystal surface.

PMID- 9910442
TI  - Pathologies in three-body molecular clusters when using delta -shell potentials.

PMID- 9910441
TI  - Size distribution of atomic clusters formed by energetic-heavy-ion sputtering.

PMID- 9910443
TI  - Cold cluster ferromagnetism.

PMID- 9910444
TI  - Incoherent time evolution on a grid of Landau-Zener anticrossings.

PMID- 9910445
TI  - Phase dependence in two-color excitation of a model atom by intense fields.

PMID- 9910447
TI  - Quantum-nondemolition measurement of photon number using radiation pressure.

PMID- 9910446
TI  - Generalized pi pulses.

PMID- 9910448
TI  - Behavior of the harmonic-generation spectrum for a short-range potential.

PMID- 9910449
TI  - Quantum sensitivity limits of an optical magnetometer based on atomic phase
      coherence.

PMID- 9910450
TI  - Two-photon absorption from a field with random telegraph frequency.

PMID- 9910451
TI  - Large-scale fluctuations in the driven Jaynes-Cummings model.

PMID- 9910452
TI  - Generalized Stokes-Mueller formalism for two-photon absorption, frequency
      doubling, and hyper-Raman scattering.

PMID- 9910453
TI  - Quantum Zeno effect in a double-well potential: A model of a physical
      measurement.

PMID- 9910454
TI  - Formation and evolution of roll patterns in optical parametric oscillators.

PMID- 9910455
TI  - Statistical properties of squeezed Kerr states.

PMID- 9910456
TI  - Transfer of correlations from squeezed states of radiation to atoms in a
      generalized Jaynes-Cummings model.

PMID- 9910457
TI  - Spatial pattern formation and instabilities in resonators with nonlinear
      dispersive media.

PMID- 9910458
TI  - Alternative integrable equations of nonlinear optics.

PMID- 9910459
TI  - Dispersionless, highly superluminal propagation in a medium with a gain doublet.

PMID- 9910460
TI  - Low-frequency pulsations in a He-Xe laser with several transverse modes:
      Experimental and numerical studies.

PMID- 9910462
TI  - Chaotic dynamics of semiconductor lasers with phase-conjugate feedback.

PMID- 9910461
TI  - Measurements of light-intensity noise during nondegenerate two-wave mixing in a
      Kerr medium.

PMID- 9910463
TI  - Propagation of quantum fluctuations in single-pass second-harmonic generation for
      arbitrary interaction length.

PMID- 9910464
TI  - Theory of high-harmonic generation by low-frequency laser fields.

PMID- 9910465
TI  - Quantum theory of continuous feedback.

PMID- 9910466
TI  - Quantum limits in interferometric gravitational-wave antennas in the presence of
      even and odd coherent states.

PMID- 9910467
TI  - Quantum-noise reduction in traveling-wave second-harmonic generation.

PMID- 9910468
TI  - Observation of Fresnel diffraction in a two-beam laser interferometer.

PMID- 9910469
TI  - Polarization dependence of tunneling ionization of helium and neon by 120-fs
      pulses at 614 nm.

PMID- 9910470
TI  - Minimum-uncertainty states for noncanonical operators.

PMID- 9910472
TI  - Additional features in the 3d-4p x-ray-emission spectrum of Xe.

PMID- 9910471
TI  - Effects of core-valence and core-core correlation on the line strength of the
      resonance lines in Li I and Na I.

PMID- 9910473
TI  - Detection of sputtered metastable atoms by autoionization.

PMID- 9910474
TI  - L1- and L2-subshell fluorescence yields of lanthanides.

PMID- 9910475
TI  - Electronic structure of small silicon clusters.

PMID- 9910477
TI  - Comment on "Lasing without inversion in a V system due to trapping of modified
      atomic states"

PMID- 9910476
TI  - Noise-induced switching and stochastic resonance in optically nonlinear CdS
      crystals.

PMID- 9910478
TI  - Erratum: Dispersion interactions between excited atoms

PMID- 9910479
TI  - Phase-sensitive dynamics of bichromatically driven two-level atoms.

PMID- 9910480
TI  - Precision measurement of the isotope shift of the 2 (3)S1-3 (3)P0 transition in
      helium.

PMID- 9910481
TI  - Zeff according to the Schwinger multichannel method in positron scattering.

PMID- 9910483
TI  - Final-state alignment from the quantum-state-selected photodissociation of K2 by
      all-optical triple resonance spectroscopy.

PMID- 9910482
TI  - Origin of the low-energy component and isotope effect on dissociative
      recombinations of HeH+ and HeD+

PMID- 9910484
TI  - Solid-state-induced energy shift of projectile Auger electrons.

PMID- 9910485
TI  - Possibility of stable spheroid molecules of ZnO.

PMID- 9910486
TI  - Interaction of half-cycle radiation pulse with Rydberg states of atomic hydrogen.

PMID- 9910487
TI  - Transient four-wave-mixing line shapes: Effects of excitation-induced dephasing.

PMID- 9910488
TI  - Wigner functions and quadrature distributions for quantum-oscillator states with
      random phase.

PMID- 9910489
TI  - Role of radiation trapping in degenerate four-wave-mixing experiments.

PMID- 9910491
TI  - Robust optimal control of quantum molecular systems in the presence of
      disturbances and uncertainties.

PMID- 9910490
TI  - Bell theorem without inequalities: A single-particle formulation.

PMID- 9910492
TI  - Theory of the hydrogen-deuterium isotope shift.

PMID- 9910493
TI  - Quantization of constraint solutions.

PMID- 9910494
TI  - Quasilinearization method applied to multidimensional quantum tunneling.

PMID- 9910496
TI  - Virtual-photon-cloud creation and emission of radiation from a dielectric slab in
      arbitrary motion.

PMID- 9910495
TI  - q-deformed binomial state.

PMID- 9910497
TI  - Modal interpretation of quantum mechanics, measurements, and macroscopic
      behavior.

PMID- 9910498
TI  - Separation of variables and exactly soluble time-dependent potentials in quantum
      mechanics.

PMID- 9910499
TI  - Alternative approach to the semiclassical description of N-fermion systems.

PMID- 9910500
TI  - Quantum effects modeled by electric circuits.

PMID- 9910501
TI  - Contractive states of a free atom.

PMID- 9910502
TI  - Semiclassical dynamics of circular-orbit Rydberg wave packets.

PMID- 9910503
TI  - Semiclassical quantization in momentum space.

PMID- 9910504
TI  - M1 decay of the 2 (3)S1 state in heliumlike krypton.

PMID- 9910506
TI  - Optical oscillator strengths of noble-gas resonance transitions in the vacuum
      ultraviolet region.

PMID- 9910505
TI  - Improvement on the correlated-Hartree-Fock method and application to atoms.

PMID- 9910507
TI  - Hyperfine splittings of neonlike lasing lines.

PMID- 9910509
TI  - Relativistic excitation energies and oscillator strengths for transitions in Zn
      like ions including core-polarization effects.

PMID- 9910508
TI  - Ion production by positron-molecule resonances.

PMID- 9910511
TI  - Universal formula to extrapolate the generalized oscillator strength through the
      unphysical region to K2=0.

PMID- 9910510
TI  - Experimental and theoretical determination of the optical and generalized
      oscillator strengths for the inner-shell excitation of C2H2.

PMID- 9910512
TI  - Hyperfine corrections to order alpha 6 in a relativistic formalism for
      positronium.

PMID- 9910513
TI  - Calculation of double-well B vibronic states of SrH.

PMID- 9910514
TI  - Exchange-correlation potential with correct asymptotic behavior.

PMID- 9910515
TI  - Two-photon transitions in atomic hydrogen: An alternative approach.

PMID- 9910516
TI  - Gauge-invariant approach to the calculation of transition probabilities for many
      electron atoms.

PMID- 9910517
TI  - Exact quantum Monte Carlo calculation of the H-He interaction potential.

PMID- 9910518
TI  - Energy levels in Ar II.

PMID- 9910519
TI  - Microwave measurements of d-f-g-h intervals and d and f fine structure of sodium
      Rydberg states.

PMID- 9910521
TI  - Calculation of resonances in doubly excited helium using the stabilization
      method.

PMID- 9910520
TI  - Dissociation energies of the hydrogen and deuterium molecules.

PMID- 9910523
TI  - Correlation-potential method for negative ions and electron scattering.

PMID- 9910522
TI  - Simple derivation of the asymptotic Casimir interaction of a pair of finite
      systems.

PMID- 9910524
TI  - Dynamic polarizabilities and van der Waals coefficients for the ground 2 (2)S and
      excited 2 (4)Po states of Li.

PMID- 9910526
TI  - Line shape of a Doppler-free two-photon transition in a metastable neon beam.

PMID- 9910525
TI  - Experimental investigation of rubidium atoms above the field-ionization limit
      using a time-resolved wave-packet approach.

PMID- 9910527
TI  - Absolute total, one-, two-, and three-electron-transfer cross sections for Arq+
      (8 <= q <= 16) on Ar at 2.3q keV.

PMID- 9910528
TI  - M-shell ionization resulting from near-central collisions of mid-Z atoms with 5.5
      MeV/amu oxygen ions.

PMID- 9910529
TI  - Resonant inelastic scattering of quasifree electrons on C5+(1s).

PMID- 9910530
TI  - Nonradiative and radiative electron capture in collisions of He+ ions with C
      atoms below 1000 eV.

PMID- 9910531
TI  - Electron-photon-correlation study of the 3 (1)D state of helium excited by
      electrons 3.5 eV above threshold.

PMID- 9910532
TI  - Ab initio complex Kohn calculations of dissociative excitation of methane: Close
      coupling convergence studies.

PMID- 9910533
TI  - Electron-impact ionization of Ar7+

PMID- 9910534
TI  - Relative excitation functions for singly-excited and core-excited levels of S V-S
      IX populated by the beam-foil interaction.

PMID- 9910535
TI  - Effects of relaxation and interchannel coupling in inner-shell photoionization of
      atomic ytterbium.

PMID- 9910536
TI  - Completion of a hybrid-theory calculation of the Pi g resonance in electron-N2
      scattering.

PMID- 9910538
TI  - Total elastic scattering cross sections for metastable argon on xenon.

PMID- 9910537
TI  - Molecular theory of collision-induced fine-structure transitions in atomic
      oxygen.

PMID- 9910539
TI  - Measurement of the H(n=2) density matrix for 20-100-keV collisions of H+ on He.

PMID- 9910541
TI  - Influence of the projectile field on free target electrons.

PMID- 9910540
TI  - Velocity-dependent total scattering cross sections for Ar(3P2,0) on H2O.

PMID- 9910542
TI  - Ab initio complex Kohn calculations of dissociative excitation of water.

PMID- 9910543
TI  - Nonadiabatic formulation of the slow-atomic-collision problem in the finite
      electronic basis.

PMID- 9910544
TI  - Calculation of electron scattering on excited states of sodium.

PMID- 9910545
TI  - Lasing in Al following photoionization and neutralization in the presence of H2:
      The role of H-

PMID- 9910546
TI  - Energy loss of swift projectiles with n (n <= 4) bound electrons.

PMID- 9910547
TI  - Energy-loss effects in multiple-scattering angular distributions of ions in
      matter.

PMID- 9910548
TI  - van der Waals interaction of finite metallic systems: A study of cluster-atom
      scattering.

PMID- 9910549
TI  - Diode-laser production of collimated slow cold potassium beams and crossover
      resonances.

PMID- 9910550
TI  - Two-photon excitation of the 5 (2)D states of rubidium.

PMID- 9910551
TI  - Two-electron molecule in weak, strong, and ultrastrong laser fields: A one
      dimensional model.

PMID- 9910552
TI  - Resonant and nonresonant multiphoton ionization of helium.

PMID- 9910553
TI  - Periodic-orbit spectroscopy of the hydrogen atom in parallel electric and
      magnetic fields.

PMID- 9910555
TI  - Transverse relaxation in spin-polarized 3He gas due to dc and ac magnetic-field
      gradients.

PMID- 9910554
TI  - Resonance collisions between three-level systems in an intense laser field.

PMID- 9910556
TI  - Analytical solutions for a resonantly driven two-doublet system.

PMID- 9910557
TI  - Self-calibrating measurement of polarization-dependent frequency shifts from Rb
      3He collisions.

PMID- 9910559
TI  - Slowing of 85Rb atoms with isotropic light.

PMID- 9910558
TI  - Laser cooling of trapped three-level ions: Designing two-level systems for
      sideband cooling.

PMID- 9910560
TI  - Generation of nonclassical light by dissipative two-photon processes.

PMID- 9910561
TI  - Simultaneous fourth-order squeezing of both quadrature components.

PMID- 9910563
TI  - Squeezing in resonance fluorescence from a trapped ion.

PMID- 9910562
TI  - Dissipative optical solitons.

PMID- 9910564
TI  - Systematic method for deriving effective Hamiltonians.

PMID- 9910565
TI  - Squeezed-light generation by twin-beam control with an optical cavity.

PMID- 9910566
TI  - Theoretical investigation of phenomena in the closed Raman-driven four-level
      symmetrical model.

PMID- 9910568
TI  - Similarity reduction and perturbation solution of the stimulated-Raman-scattering
      equations in the presence of dissipation.

PMID- 9910567
TI  - Quantum-mechanical approach to a free photon.

PMID- 9910570
TI  - Observation of the stochastic realization shift in the weak-field limit.

PMID- 9910569
TI  - Photoionization of the hydrogen 4s state by a strong laser pulse: Bare-state
      dynamics and extended-charge-cloud oscillations.

PMID- 9910571
TI  - Vectorial nonlinear dynamics in lasers with one or two stable eigenstates.

PMID- 9910572
TI  - Squeezing of intensity fluctuations in frequency summation.

PMID- 9910573
TI  - Pattern formation and competition in nonlinear optical systems with two
      dimensional feedback.

PMID- 9910574
TI  - Stability and switching in whispering-gallery-mode microdisk lasers.

PMID- 9910575
TI  - Gain and diffusion in an inversionless laser.

PMID- 9910576
TI  - Collisional decay and revival of the grating stimulated echo.

PMID- 9910577
TI  - Quantum cooperative effects in a micromaser.

PMID- 9910578
TI  - Optical pulse propagation at negative group velocities due to a nearby gain line.

PMID- 9910579
TI  - Spatial properties of spontaneous parametric down-conversion and their effect on
      induced coherence without induced emission.

PMID- 9910580
TI  - One-atom maser: Statistics of detector clicks.

PMID- 9910582
TI  - Photon distribution for one-mode mixed light with a generic Gaussian Wigner
      function.

PMID- 9910581
TI  - Phase squeezing in two-photon correlated-spontaneous-emission lasers.

PMID- 9910583
TI  - Effects of different phase-matching conditions in sum-frequency-mixing systems in
      vapors.

PMID- 9910585
TI  - Lower bounds on phase sensitivity in ideal and feasible measurements.

PMID- 9910584
TI  - Theory of adiabatic cooling in cavities.

PMID- 9910586
TI  - Evanescently induced optical switching between bistable soliton states of the
      second kind.

PMID- 9910588
TI  - Completeness and orthogonality of quasinormal modes in leaky optical cavities.

PMID- 9910587
TI  - Revivals and superstructures in the Jaynes-Cummings model with a small number of
      photons.

PMID- 9910590
TI  - Relativistic density-functional theory for ensembles of excited states.

PMID- 9910589
TI  - Time-independent perturbation theory for quasinormal modes in leaky optical
      cavities.

PMID- 9910591
TI  - Experimental studies of the length dependence of second-order nonlinear optical
      responses of conjugated molecules.

PMID- 9910592
TI  - Upper bounds to the electron-electron coalescence density in terms of the one
      electron density function.

PMID- 9910593
TI  - Small-angle differential cross sections for Xe 5p5(2P3/2)6s.

PMID- 9910595
TI  - dc-field tunneling of polyelectronic atoms and of negative ions: Computations
      based on models and on ab initio theory.

PMID- 9910594
TI  - Z scaling of the 3P-3S Li isoelectronic series transition: Quadrupole Stark
      broadening and resonances.

PMID- 9910597
TI  - Observation of chemical-fusion reactions of fullerenes in the negative-ion
      channel.

PMID- 9910596
TI  - Heavy-particle excitation of fluorinelike Fe XVIII.

PMID- 9910598
TI  - Velocity-tuned resonances in the diffraction of atoms by an evanescent field.

PMID- 9910599
TI  - Configuration interaction in argon KL resonances.

PMID- 9910600
TI  - Higher-harmonic generation from a metal surface in a powerful laser field.

PMID- 9910601
TI  - Two-color ionization of hydrogen for frequencies in the 2:3 ratio.

PMID- 9910602
TI  - Effects of correlation between inhomogeneously broadened transitions on quantum
      beats in transient four-wave mixing.

PMID- 9910603
TI  - Laser modes with helical wave fronts.

PMID- 9910604
TI  - Resonant-line overlap for photopumping and spoiling of x-ray lasing transitions
      in neonlike Fe XVII and Cu XX.

PMID- 9910606
TI  - Comment on "Suppressed electron capture in slow O+(4So,2Do,2Po)-He collisions"

PMID- 9910605
TI  - Coherent evolution after the relaxation time.

PMID- 9910607
TI  - Reply to "Comment on 'Lasing without inversion in a V system due to trapping of
      modified atomic states' "

PMID- 9910608
TI  - Erratum: Fusion yields for carbon-cluster impact on CD2 targets

PMID- 9910609
TI  - Talbot-vonLau atom interferometry with cold slow potassium.

PMID- 9910610
TI  - Nonadiabatic transitions and gauge structure.

PMID- 9910611
TI  - Precision measurement of Stark shifts for 6P3/2-->nS1/2 n=10-13 transitions in
      cesium.

PMID- 9910612
TI  - Calculation of the total and total ionization cross sections for positron
      scattering on atomic hydrogen.

PMID- 9910613
TI  - Conical emission as cooperative fluorescence.

PMID- 9910615
TI  - Unitarity and electron-positron pairs created by strong external fields.

PMID- 9910614
TI  - Strong versions of Bell's theorem.

PMID- 9910616
TI  - Spectral modulation and squeezing at high-order neutron interferences.

PMID- 9910617
TI  - Precise measurements of e+e- annihilation at rest into four photons and the
      search for exotic particles.

PMID- 9910618
TI  - Proposal for a loophole-free Bell inequality experiment.

PMID- 9910619
TI  - Nonlocal reduction of the wave function by quantum phase measurements.

PMID- 9910620
TI  - Geometric phase and sequential measurements in quantum mechanics.

PMID- 9910621
TI  - Principles of the first and second kind of balance in a varying-parameters method
      for eigenvalue problems in quantum mechanics.

PMID- 9910622
TI  - Weyl-Wigner formalism for rotation-angle and angular-momentum variables in
      quantum mechanics.

PMID- 9910623
TI  - Semiclassical quantum theory and its applications in two dimensions by conformal
      mapping.

PMID- 9910625
TI  - Phase-integral approach to quantal two- and three-dimensional isotropic
      anharmonic oscillators.

PMID- 9910624
TI  - Tunneling delay times in one and two dimensions.

PMID- 9910626
TI  - One-dimensional scattering: Recurrence relations and differential equations for
      transmission and reflection amplitudes.

PMID- 9910627
TI  - Three-photon excitation of autoionizing states of Ar, Kr, and Xe between the
      2P3/2 and 2P1/2 ionic limits.

PMID- 9910628
TI  - Investigation of some transitions and lifetimes in Xe II.

PMID- 9910630
TI  - Nonvariational calculation of the relativistic and finite-size corrections for
      the helium ground state.

PMID- 9910629
TI  - Nonvariational calculation of the relativistic, finite-size, and QED corrections
      for the 2 (1)S excited state of the helium atom.

PMID- 9910631
TI  - Isotope shifts and hyperfine structure in the 369.4-nm 6s-6p1/2 resonance line of
      singly ionized ytterbium.

PMID- 9910633
TI  - Anapole moment of a diatomic polar molecule.

PMID- 9910632
TI  - Momentum-transfer dispersion relations for electron-atom cross sections.

PMID- 9910635
TI  - Effects of Zeeman degeneracy on the steady-state properties of an atom
      interacting with a near-resonant laser field: Probe spectra.

PMID- 9910634
TI  - Exchange integrals: Comparison of numerical and analytical procedures.

PMID- 9910636
TI  - Measurement of vibrational line profiles in H2-rare-gas mixtures: Determination
      of the speed dependence of the line shift.

PMID- 9910638
TI  - Measurement of oscillator strengths of the principal series of calcium.

PMID- 9910637
TI  - Consistency of approximation schemes in many-body theory.

PMID- 9910639
TI  - Lifetimes and transition probabilities of the boron atom calculated with the
      active-space multiconfiguration Hartree-Fock method.

PMID- 9910640
TI  - Canonical density matrix for free electrons moving on a spherical surface.

PMID- 9910641
TI  - Energy-density relationships for the treatment of ion solvation within density
      functional theory.

PMID- 9910643
TI  - Observation of a Mg XI forbidden satellite line in an optically thick X-pinch
      plasma.

PMID- 9910642
TI  - Theoretical study of the magnetic properties of a methane molecule in a
      nonuniform magnetic field.

PMID- 9910644
TI  - Finite-element multiconfiguration Hartree-Fock calculations of the atomic
      quadrupole moments of C+(2P) and Ne+(2P).

PMID- 9910646
TI  - Excited-level lifetimes and hyperfine-structure measurements on ions using
      collinear laser-ion-beam spectroscopy.

PMID- 9910645
TI  - Electron-pair wave packets.

PMID- 9910647
TI  - Mean-lifetime calculations of the metastable doubly charged NeAr2+ rare-gas
      dimer.

PMID- 9910648
TI  - Application of Hilbert-space coupled-cluster theory to simple (H2)2 model
      systems. II. Nonplanar models.

PMID- 9910649
TI  - Isotropic and anisotropic static dipole polarizabilities of the first-row stable
      atomic anions.

PMID- 9910651
TI  - Level statistics for continuous energy spectra with application to the hydrogen
      atom in crossed electric and magnetic fields.

PMID- 9910650
TI  - Relativistic all-order many-body calculations of the n=1 and n=2 states of
      heliumlike ions.

PMID- 9910652
TI  - Effect of magnetic fine structure and mixing on the radiative lifetimes and the
      polarizabilities of excited states of helium.

PMID- 9910654
TI  - Broadening and shifts of the lines of molecular ions by collisions with neutral
      perturbers.

PMID- 9910653
TI  - Cascade-free Doppler-tuned precision measurement of the lifetime of the 2 (3)S1
      state in He-like niobium (93Nb39+).

PMID- 9910655
TI  - Muon transfer from excited muonic hydrogen to helium.

PMID- 9910656
TI  - Stability of the hydrogen and hydrogenlike molecules.

PMID- 9910657
TI  - One-photon annihilation in the Ps- ion and the angular (e-,e-) correlation in two
      electron ions.

PMID- 9910659
TI  - Double ionization of He(1s2) and He(1s2s 3S) by a single high-energy photon.

PMID- 9910658
TI  - Multielectron processes in 10-keV/u Arq+ (5 <= q <= 17) on Ar collisions.

PMID- 9910660
TI  - Collision integral for ionization by electron impact for nonisotropic electron
      distribution functions.

PMID- 9910662
TI  - Two-electron capture from helium by fast alpha particles.

PMID- 9910661
TI  - Low-energy-electron collisions with sodium: Elastic and inelastic scattering from
      the ground state.

PMID- 9910664
TI  - Elastic scattering of 81-keV gamma rays.

PMID- 9910663
TI  - Shape resonances in e--H scattering above the hydrogen N=4 threshold.

PMID- 9910665
TI  - Finite-element analysis of electron-hydrogen scattering.

PMID- 9910666
TI  - Differential excitation cross sections of molecular oxygen by electron impact:
      The longest and second bands.

PMID- 9910667
TI  - Electronic decay processes of photoexcited 2p resonances of atomic Ar, K, and Ca.

PMID- 9910669
TI  - Time-independent scattering theory for time-periodic Hamiltonians: Formulation
      and complex-scaling calculations of above-threshold-ionization spectra.

PMID- 9910668
TI  - Use of the factorized form for the collision strength in exploration of the
      effect of the generalized Breit interaction.

PMID- 9910670
TI  - Calculation of the electric potential around two identical atoms or ions.

PMID- 9910671
TI  - Asymptotic theory of s-->p charge exchange: Extended Demkov model.

PMID- 9910672
TI  - Double-electron excitation of H- by fast proton and antiproton impact.

PMID- 9910674
TI  - Amplitudes at nuclei of electronic wave functions for atomic ions.

PMID- 9910673
TI  - Phase-amplitude method applied to doubly excited states of He (1Se).

PMID- 9910675
TI  - Intense-field molecular spectroscopy: Vibrational and rotational effects in
      harmonic generation by H2+

PMID- 9910676
TI  - Inversion of electron-water elastic-scattering data.

PMID- 9910677
TI  - Quantum field theory of interaction of ultracold atoms with a light wave: Bragg
      scattering in nonlinear atom optics.

PMID- 9910678
TI  - Reflection of metastable argon atoms from an evanescent wave.

PMID- 9910679
TI  - Atomic Bose gas with a negative scattering length.

PMID- 9910680
TI  - Microwave ionization of Rb Rydberg atoms: Frequency dependence.

PMID- 9910682
TI  - Laser optical pumping of high-density Rb in polarized 3He targets.

PMID- 9910681
TI  - Electrostatic modes as a diagnostic in Penning-trap experiments.

PMID- 9910683
TI  - Excitation and ionization dynamics in short-pulse multiphoton ionization.

PMID- 9910684
TI  - Channel closing in multiphoton ionization of Mg.

PMID- 9910685
TI  - High-order harmonic generation and ionization using ultrashort KrF and
      Ti:sapphire lasers.

PMID- 9910686
TI  - Complex-potential model of collisions of laser-cooled atoms.

PMID- 9910687
TI  - Excited-state survival probabilities for cold collisions in a weak laser field.

PMID- 9910688
TI  - Norm of the wave function on a complex basis.

PMID- 9910689
TI  - Light-pressure force in N-atom systems.

PMID- 9910690
TI  - Contribution of energy continuum states to probe the absorption signal of atoms
      in one-dimensional optical molasses.

PMID- 9910691
TI  - Photon-emission spectra of the H2+ molecular ion in an intense laser field.

PMID- 9910692
TI  - Filtering of two-photon quantum correlations by optical cavities: Cancellation of
      dispersive effects.

PMID- 9910693
TI  - Residual energy and its effect on gain in a Lyman- alpha laser.

PMID- 9910694
TI  - Codimension-two two-hard-mode bifurcation and coexistence of multiple attractors
      in a two-photon laser with an injected signal.

PMID- 9910695
TI  - Theory of doubly resonant infrared-visible sum-frequency and difference-frequency
      generation from adsorbed molecules.

PMID- 9910697
TI  - Explanation of the cw operation of the Er3+ 3- microm crystal laser.

PMID- 9910696
TI  - Completeness and time-independent perturbation of the quasinormal modes of an
      absorptive and leaky cavity.

PMID- 9910698
TI  - Dynamics of an erbium-doped fiber laser.

PMID- 9910699
TI  - Two-photon emission spectrum of a two-level atom in an ideal cavity.

PMID- 9910700
TI  - Intensity characteristics of inversionless lasers from induced atomic coherence.

PMID- 9910701
TI  - Calculations of a high-gain recombination x-ray laser at 4.55 nm.

PMID- 9910702
TI  - Rabi resonance in frequency conversion by four-wave mixing in lasers and its
      connection with the multimode laser instability.

PMID- 9910703
TI  - Photon-number correlations near the threshold of microcavity lasers in the weak
      coupling regime.

PMID- 9910705
TI  - Quantum noise reduction by radiation pressure.

PMID- 9910704
TI  - Theory of a multimode photorefractive oscillator: Quantitative results on the
      frequency shift.

PMID- 9910706
TI  - Phase-matching techniques and frequency-conversion efficiency in optically active
      crystals.

PMID- 9910708
TI  - Self-focusing of chirped optical pulses in nonlinear dispersive media.

PMID- 9910707
TI  - State preparation via quantum coherence and continuous measurement.

PMID- 9910709
TI  - Phase-sensitive above-threshold laser amplifiers.

PMID- 9910710
TI  - Wigner distribution of a general angular-momentum state: Applications to a
      collection of two-level atoms.

PMID- 9910711
TI  - All-optical versus electro-optical quantum-limited feedback.

PMID- 9910712
TI  - Quantum-noise reduction in Raman lasers: Effects of collisions, population
      trapping, and Doppler shifts.

PMID- 9910713
TI  - Squeezing from ghost transitions.

PMID- 9910715
TI  - Radiation trapping: An alternative mechanism for chaos in a nonlinear optical
      resonator.

PMID- 9910714
TI  - Theory of electron-counting processes.

PMID- 9910716
TI  - Neoclassical radiation theory as an integral part of the Monte Carlo wave
      function method.

PMID- 9910718
TI  - Quantum scattering of a two-level atom in the limit of large detuning.

PMID- 9910717
TI  - Controlling the degree of visibility of Young's fringes with photon coincidence
      measurements.

PMID- 9910719
TI  - Nonlinear transverse modes of large-aspect-ratio homogeneously broadened lasers:
      I. Analysis and numerical simulation.

PMID- 9910720
TI  - Nonlinear transverse modes of large-aspect-ratio homogeneously broadened lasers:
      II. Pattern analysis near and beyond threshold.

PMID- 9910721
TI  - Triorthogonal uniqueness theorem and its relevance to the interpretation of
      quantum mechanics.

PMID- 9910722
TI  - Graphical method for operating in second quantization.

PMID- 9910723
TI  - Pion transfer from hydrogen to deuterium in H2O+D2O mixtures.

PMID- 9910724
TI  - Atomic-charge monotonicity and cusp-type inequalities: Applications to heliumlike
      systems.

PMID- 9910725
TI  - Density differences for near-Hartree-Fock atomic wave functions.

PMID- 9910726
TI  - Sodium excitation by spin-polarized electrons: A reanalysis of existing
      experiments.

PMID- 9910727
TI  - Li5 as a pseudorotating planar cluster.

PMID- 9910728
TI  - Simple quantum-mechanical picture of cold optical collisions.

PMID- 9910729
TI  - Two-photon interference in a standard Mach-Zehnder interferometer.

PMID- 9910730
TI  - Phase and photon-number squeezings in a many-cascade two-photon correlated
      spontaneous-emission laser.

PMID- 9910731
TI  - Stapp's algebraic argument for nonlocality.

PMID- 9910732
TI  - Reply to "Stapp's algebraic argument for nonlocality"

PMID- 9910733
TI  - Optical test of local hidden-variable theories with two-channel polarizers.

PMID- 9910734
TI  - Mechanism for fragmentation of molecules by positron annihilation.

PMID- 9910735
TI  - Internal energy deposition into molecules upon positron-electron annihilation.

PMID- 9910736
TI  - Projectile-charge-state dependence of 0 degrees binary-encounter electron
      production in 30-MeV Oq++O2 collisions.

PMID- 9910737
TI  - Theory of resonances and bound-state management.

PMID- 9910739
TI  - Competing nonlinearities.

PMID- 9910738
TI  - Decomposition of experimentally determined atomic (e,2e) ionization measurements.

PMID- 9910741
TI  - Nonclassical states of motion in a three-dimensional ion trap by adiabatic
      passage.

PMID- 9910740
TI  - Stability of three-dimensional self-trapped beams with a dark spot surrounded by
      bright rings of varying intensity.

PMID- 9910742
TI  - Light-shift-induced spatial structures: Application to degenerate four-wave
      mixing.

PMID- 9910743
TI  - Inverse-square potential and the quantum vortex.

PMID- 9910744
TI  - Systematic approach to define and classify quantum transmission and reflection
      times.

PMID- 9910745
TI  - Quantum inverse problem for the derivative nonlinear Schrodinger equation.

PMID- 9910746
TI  - Causality constraints on nonlocal quantum measurements.

PMID- 9910747
TI  - Evolution of a two-level system with relaxation driven by a time-dependent
      Hamiltonian: A simple model.

PMID- 9910748
TI  - Complementary electric Aharonov-Bohm effect.

PMID- 9910749
TI  - Multichannel quantum-defect theory of double-minimum 1 Sigma g+ states in H2. I.
      Potential-energy curves.

PMID- 9910750
TI  - Multichannel quantum-defect theory of double-minimum 1 Sigma g+ states in H2. II.
      Vibronic-energy levels.

PMID- 9910751
TI  - Resonant inelastic x-ray scattering with symmetry-selective excitation.

PMID- 9910752
TI  - Measurement of 1s2s 3S1-1s2p 3P2,0 wavelengths in heliumlike silicon.

PMID- 9910753
TI  - J dependences of the isotope shift and hyperfine structure in the Sm I 4f65d6s 9H
      term.

PMID- 9910754
TI  - Finite-element computation of perturbation energies for the two-electron atom.

PMID- 9910755
TI  - Quantum Monte Carlo calculation of the Fe atom.

PMID- 9910756
TI  - Charged anisotropic harmonic oscillator and the hydrogen atom in crossed fields.

PMID- 9910757
TI  - Decay of the resonantly excited states of atomic Zn.

PMID- 9910758
TI  - Three-body molecular formation in muon-catalyzed d-t fusion: The classical
      trajectory model.

PMID- 9910759
TI  - Test of the multichannel quantum-defect wave function by a Lande-factor (gJ)
      investigation in the perturbed 6snp 1,3P1 sequences of Yb I.

PMID- 9910760
TI  - Application of a two-step method to the vibrational rotational spectrum of
      diatomic molecules.

PMID- 9910761
TI  - Delayed annihilation of antiprotons in helium gas.

PMID- 9910762
TI  - 4Po series of lithium.

PMID- 9910763
TI  - Calculation of doubly excited states of helium with a finite discrete spectrum.

PMID- 9910764
TI  - Variational calculations for the dt micro molecule including nuclear effects on
      sticking by means of the Bloch operator.

PMID- 9910766
TI  - Enhancement of the electric dipole moment of the electron in the YbF molecule.

PMID- 9910765
TI  - Calculation formulas for the reducible part of the two-photon-exchange diagrams
      in the QED of multicharged ions.

PMID- 9910768
TI  - Some calculations on the ground and lowest-triplet state of helium in the fixed
      nucleus approximation.

PMID- 9910767
TI  - Three-body induced dipole moments and infrared absorption: The H2 fundamental
      band.

PMID- 9910769
TI  - Some calculations on the ground and lowest-triplet state of the helium
      isoelectronic sequence with the nucleus in motion.

PMID- 9910770
TI  - Magnetic-field dependence of the cross section for mJ mixing in 2P1/2 Cs and Rb
      atoms.

PMID- 9910771
TI  - Applications of square-integrable basis functions for scattering problems: A
      comparison between approaches based on Toeplitz matrices and negative imaginary
      potentials.

PMID- 9910773
TI  - Ab initio results of adiabatic stability of the hydrogen atom.

PMID- 9910774
TI  - Near-threshold behavior of the K-shell satellites in CO.

PMID- 9910775
TI  - Measurements of cross sections and oscillator strengths for Ne by electron-energy
      loss spectroscopy.

PMID- 9910772
TI  - Analysis of charge-state-correlated multiple-capture and -ionization cross
      sections in fast Arq+-Ar collisions.

PMID- 9910776
TI  - Merged-beams energy-loss technique for electron-ion excitation: Absolute total
      cross sections for O5+(2s-->2p).

PMID- 9910778
TI  - Three-body depolarized interaction-induced light-scattering spectrum of neon.

PMID- 9910777
TI  - Equivalent-local calculation of the continuum contributions to electron and
      positron reactions on atoms.

PMID- 9910779
TI  - Dissociative recombination of HeH+: A reexamination.

PMID- 9910780
TI  - L-subshell ionization cross sections in gold and bismuth by 3.6-9.5-MeV carbon
      and 4.0-7.2-MeV oxygen ions.

PMID- 9910781
TI  - Distorted-wave Born approximation calculations of the pair-production cross
      section for 6.0-MeV photons.

PMID- 9910782
TI  - Atomic supersymmetry, Rydberg wave packets, and radial squeezed states.

PMID- 9910783
TI  - Relativistic effect of atomic radiative processes.

PMID- 9910784
TI  - Momentum-space calculation of electron-molecule scattering.

PMID- 9910785
TI  - Coherence and correlation in the anisotropy of Ne KL-LLL satellite Auger decay.

PMID- 9910786
TI  - Energy-resolved intramultiplet mixing in the electron-volt range for
      Ne**{(2p)5(3p)}+He.

PMID- 9910787
TI  - Absolute cross sections for electron-impact single ionization of Kr4+, Kr5+, and
      Kr7+ ions.

PMID- 9910788
TI  - Excitation-autoionization contributions to the electron-impact ionization of Kr4+
      Kr7+

PMID- 9910789
TI  - Electron emission and image-charge acceleration for the impact of very highly
      charged ions on clean gold.

PMID- 9910790
TI  - Deexcitation of helium 2 (3)S, 2 (1)S, and 2 (3)P atoms at Ar and Xe films.

PMID- 9910791
TI  - Statistics of energy loss and charge exchange of penetrating particles: Higher
      moments and transients.

PMID- 9910792
TI  - Local theory of Auger neutralization for slow and compact ions interacting with
      metal surfaces.

PMID- 9910793
TI  - Dynamical effects in atom optics.

PMID- 9910794
TI  - Doppler-tuned multiphoton resonances in an atom reflection by a standing
      evanescent wave.

PMID- 9910795
TI  - Effect of the pumping-field amplitude and phase modulation on the weak-probe
      absorption and dispersion spectra in a two-level medium.

PMID- 9910796
TI  - Experimental investigations of the absorption and dispersion profiles of a
      strongly driven transition: Two-level system with a weak probe.

PMID- 9910798
TI  - Infrared radiation by a Dirac electron: First-order correction to the cross
      section sum rule.

PMID- 9910797
TI  - Non-Franck-Condon vibrational distribution in the (1+1')-photon resonance
      enhanced multiphoton ionization of H2.

PMID- 9910799
TI  - Collisionless motion of neutral particles in magnetostatic traps.

PMID- 9910800
TI  - Microwave ionization of hydrogen Rydberg atoms: Resonance analysis and critical
      fields.

PMID- 9910801
TI  - Strong-field effects in coherent saturation spectroscopy of atomic beams.

PMID- 9910802
TI  - Polarization-gradient-assisted subrecoil cooling: Quantum calculations in one
      dimension.

PMID- 9910803
TI  - Atomic hydrogen in a strong optical radiation field.

PMID- 9910804
TI  - Born-Floquet theory of laser-assisted electron-atom collisions.

PMID- 9910805
TI  - Three-dimensional theory of the magneto-optical trap: Doppler cooling in the low
      intensity limit.

PMID- 9910806
TI  - Cooling and localization of atoms in laser-induced potential wells.

PMID- 9910808
TI  - Four-wave mixing in strongly driven two-level systems.

PMID- 9910807
TI  - Superoperators and their implications in the hybrid model for photodetection.

PMID- 9910809
TI  - Quantum-nondemolition measurement and squeezing in type-II harmonic generation
      with triple resonance.

PMID- 9910810
TI  - Very small optimized phase uncertainties of two-photon coherent states.

PMID- 9910811
TI  - Nonlinear interaction of transverse modes in a CO2 laser.

PMID- 9910813
TI  - Generalization of the Maxwell-Bloch equations to the case of strong atom-field
      coupling.

PMID- 9910812
TI  - Holographic nondiverging hollow beam.

PMID- 9910814
TI  - Time evolution of harmonic oscillators with time-dependent parameters: A step
      function approximation.

PMID- 9910815
TI  - Quantum chaos of atoms in a resonator driven by an external resonant field.

PMID- 9910816
TI  - Photon distribution in two-mode squeezed coherent states with complex
      displacement and squeeze parameters.

PMID- 9910817
TI  - Atomic states with spectroscopic squeezing.

PMID- 9910818
TI  - General properties of quantum optical systems in a strong-field limit.

PMID- 9910819
TI  - Bistability in a four-level laser with a resonant pump mode.

PMID- 9910820
TI  - Phase properties of optical linear amplifiers.

PMID- 9910821
TI  - Theory of second-harmonic generation of molecular systems: The case of coincident
      pulses.

PMID- 9910823
TI  - One-atom maser with a periodic and noisy pump: An application of damping bases.

PMID- 9910822
TI  - Time-dependent micromaser spectrum.

PMID- 9910825
TI  - Schrodinger equation description for cross-phase modulation in grating
      structures.

PMID- 9910824
TI  - Tunneling in the presence of driving in a cavity that contains a Kerr medium and
      is parametrically pumped.

PMID- 9910826
TI  - Phase uncertainties of a squeezed state.

PMID- 9910828
TI  - Quasicontinuous measurements of photon number.

PMID- 9910827
TI  - Laser-noise-induced polarization fluctuations as a spectroscopic tool.

PMID- 9910829
TI  - Nonlinear quantum spin dynamics: Symmetries without conservation laws.

PMID- 9910830
TI  - Improved Hill determinant method for the solution of quantum anharmonic
      oscillators.

PMID- 9910831
TI  - Gauge-invariant Berry phase and quasienergy for a charged system in an
      electromagnetic field.

PMID- 9910832
TI  - delta ' potential arising in exterior complex scaling.

PMID- 9910833
TI  - Conditionally exactly soluble potentials and supersymmetry.

PMID- 9910834
TI  - Necessary condition for an atom-positron bound state.

PMID- 9910835
TI  - Dynamic dipole polarizabilities of rubidium.

PMID- 9910836
TI  - Quadrupole toroidal moment of positronium.

PMID- 9910837
TI  - Electron-capture processes in the collision of metastable B3+(1s2s) on atomic
      hydrogen.

PMID- 9910838
TI  - Charge-state dependence of electron emission in 30-MeV Oq++O2 collisions.

PMID- 9910839
TI  - Hidden Fano interferences in the resonant photoionization of He-like ions.

PMID- 9910840
TI  - Scaling laws in double photoionization.

PMID- 9910842
TI  - Precise measurement of the Stark shift of the rubidium and potassium D1 lines.

PMID- 9910841
TI  - Kr M4,5N2,3-N2,3N2,3N2,3 and Xe N4,5O2,3-O2,3O2,3O2,3 satellite Auger spectra
      following direct double ionization.

PMID- 9910843
TI  - Geometric phase with photon statistics and squeezed light for the dispersive
      fiber.

PMID- 9910844
TI  - Light amplification without population inversion: Time-dependent study of (1+1)
      photon emission from autoionizing states.

PMID- 9910845
TI  - Exact solution for quantum revivals in a fiber having a Kerr nonlinearity.

PMID- 9910846
TI  - Bistability and intensity-noise quenching in the single-atom two-photon laser
      without inversion.

PMID- 9910847
TI  - Squeezed states and Shannon entropy.

PMID- 9910848
TI  - Nonideal lasers, nonclassical light, and deformed photon states.

PMID- 9910849
TI  - Comment on "Local exchange-correlation functional: Numerical test for atoms and
      ions"

PMID- 9910850
TI  - Reply to "Comment on 'Local exchange-correlation functional: Numerical test for
      atoms and ions' "

PMID- 9910852
TI  - Erratum: Fast inelastic ion-ion, ion-electron, and ion-positron collisions

PMID- 9910851
TI  - Erratum: Moments of P functions and nonclassical depths of quantum states

PMID- 9910853
TI  - Erratum: Quantum theory of continuous feedback

PMID- 9910854
TI  - Electron correlation in Xe 4d5/2-16p-->5p-26p resonant Auger transitions studied
      by utilizing the Auger resonant Raman effect.

PMID- 9910855
TI  - Harmonic-oscillator structure of classically unstable motion.

PMID- 9910856
TI  - Dissociative recombination without a curve crossing.

PMID- 9910857
TI  - Single and double ionization of He by slow protons and antiprotons.

PMID- 9910858
TI  - Role of collisions in the search for an electron electric-dipole moment.

PMID- 9910859
TI  - Ionization of hydrogen by positron impact near the fragmentation threshold.

PMID- 9910860
TI  - van der Waals forces between metal microclusters and fullerenes.

PMID- 9910862
TI  - Observation of gain due to coherence effects in a potassium-helium mixture.

PMID- 9910861
TI  - Two-dimensional Sisyphus cooling in a three-beam laser configuration.

PMID- 9910863
TI  - Theoretical model of a purported empirical violation of the predictions of
      quantum theory.

PMID- 9910864
TI  - Two-photon entanglement in type-II parametric down-conversion.

PMID- 9910865
TI  - Approximate treatment of the Dirac equation with scalar and vector potentials of
      rectangular shapes.

PMID- 9910866
TI  - Low-intensity laser-electron scattering in the Thomson limit.

PMID- 9910867
TI  - Squeezed states, metaplectic group, and operator Mobius transformations.

PMID- 9910868
TI  - Testing Einstein-Podolsky-Rosen assumptions without inequalities with two photons
      or particles with spin 1/2.

PMID- 9910869
TI  - Squeezed atomic states and projection noise in spectroscopy.

PMID- 9910871
TI  - Semiclassical density of states at symmetric pitchfork bifurcations in coupled
      quartic oscillators.

PMID- 9910870
TI  - Anomalous commutation relation and modified spontaneous emission inside a
      microcavity.

PMID- 9910872
TI  - Centrifugal force: A gedanken experiment.

PMID- 9910873
TI  - Derivation of the modified Schrodinger equation for a particle with a spatially
      varying mass through path integrals.

PMID- 9910874
TI  - Coherent light scattering in isotropic media: Theory of degenerate four-wave
      mixing in vibrational spectroscopy.

PMID- 9910876
TI  - Linewidths of photoinduced L x rays of uranium.

PMID- 9910875
TI  - Vacuum-polarization contribution to the hyperfine-structure splitting of
      hydrogenlike atoms.

PMID- 9910877
TI  - Experimental investigation of excited states in atomic dysprosium.

PMID- 9910878
TI  - alpha 2(Z alpha )5m contribution to the hydrogen Lamb shift from virtual light-by
      light scattering.

PMID- 9910879
TI  - Self-consistent-field calculations of atoms and ions using a modified local
      density approximation.

PMID- 9910881
TI  - Spin-dependent operators in the unitary-group approach.

PMID- 9910880
TI  - Measured lifetimes of selected metastable levels of Arq+ ions (q=2, 3, 9, and 10)
      stored in an electrostatic ion trap.

PMID- 9910882
TI  - Exact Kohn-Sham scheme based on perturbation theory.

PMID- 9910883
TI  - Dipole radiative rates of metastable antiprotonic helium.

PMID- 9910884
TI  - Determination of radiative lifetimes of excited states in neutral gold using time
      resolved vacuum-ultraviolet laser spectroscopy.

PMID- 9910886
TI  - Variational calculations for the bound-unbound transition of the Yukawa
      potential.

PMID- 9910885
TI  - Muonium spin exchange in spin-polarized media: Spin-flip and -nonflip collisions.

PMID- 9910887
TI  - Hyperspherical coupled-channel study of positronium formation.

PMID- 9910888
TI  - Maximum-entropy analysis of the electron-pair density in many-electron systems.

PMID- 9910889
TI  - Relativistic configuration-interaction calculations for the ground state and n=2
      singlet states of heliumlike ions.

PMID- 9910890
TI  - Weizsacker energy of many-electron systems.

PMID- 9910891
TI  - Structure of compound states in the chaotic spectrum of the Ce atom: Localization
      properties, matrix elements, and enhancement of weak perturbations.

PMID- 9910892
TI  - Validity of the extended electron-electron cusp condition.

PMID- 9910894
TI  - Information entropy and uncertainty in D-dimensional many-body systems.

PMID- 9910893
TI  - Low-energy nuclear transfer reactions in muonic molecules.

PMID- 9910895
TI  - Non-Born-Oppenheimer correction to the H3+ potential from experimental data.

PMID- 9910896
TI  - Fluorescence spectroscopy of C60 at room temperature.

PMID- 9910897
TI  - Time-dependent many-electron approach to slow ion-atom collisions: The coupling
      of electronic and nuclear motions.

PMID- 9910899
TI  - Calculation of pair production by photons of energies near threshold on atoms.

PMID- 9910898
TI  - Differential transfer ionization cross sections for 50-175-keV proton-helium
      collisions.

PMID- 9910900
TI  - Inelastic atomic scattering by high-energy photons and charged particles.

PMID- 9910901
TI  - Electron-impact ionization of a hydrogenic ion.

PMID- 9910902
TI  - Study of electron-molecule collisions via the finite-element method and R-matrix
      propagation technique: Model exchange.

PMID- 9910903
TI  - Forward electron emission in Cq+-He collisions.

PMID- 9910904
TI  - Minimum principle for Dirac scattering lengths.

PMID- 9910906
TI  - Photoionization of magnesium including double excitations.

PMID- 9910905
TI  - Numerical study of autoionizing states in completely correlated two-electron
      systems.

PMID- 9910907
TI  - Elastic scattering of two 7Li atoms.

PMID- 9910908
TI  - Cascade effects on the Ar LMM Auger spectrum.

PMID- 9910909
TI  - Implementation of nonseparable exact exchange effects in the first-order
      nondegenerate adiabatic theory.

PMID- 9910910
TI  - Common-translation-factor method with an atomic basis.

PMID- 9910911
TI  - Polarization spectra of excited-state-Mg(3p)-rare-gas-atom optical collisions.

PMID- 9910912
TI  - Angular-momentum transfer in collisional ionization.

PMID- 9910914
TI  - Measurements of cross sections for electron-impact excitation into the metastable
      levels of argon and number densities of metastable argon atoms.

PMID- 9910913
TI  - Application of the generalized scattering amplitude in quantum potential
      scatterings.

PMID- 9910915
TI  - Angular distributions for single- and double-electron capture in slow C4+-Ne
      collisions.

PMID- 9910916
TI  - Adiabatic theory of Wannier threshold laws and ionization cross sections.

PMID- 9910917
TI  - Collision-induced absorption by H2 pairs in the fundamental band at 78 and 298 K.

PMID- 9910918
TI  - Spin-polarization spectroscopy of Auger electrons and photoelectrons in 5p
      ionization of barium atoms.

PMID- 9910919
TI  - Resonant charge transfer in collisions between positive ions.

PMID- 9910920
TI  - Evidence for population of highly asymmetric states in double-electron capture by
      O7,8+ and N7+ colliding with He at low to intermediate velocities.

PMID- 9910921
TI  - Calculations of Q values in single- and double-charge-transfer collisions of
      highly charged ions with atoms.

PMID- 9910923
TI  - Kinetics of excited muonic hydrogen.

PMID- 9910922
TI  - Muon transfer in excited muonic hydrogen.

PMID- 9910924
TI  - Atomic structure calculations of KLL Auger spectra from highly charged ion-solid
      surface collisions.

PMID- 9910925
TI  - General method to solve Hamiltonians with infinite-range interactions.

PMID- 9910926
TI  - Geometry and bonding in alkali-metal-atom-antimony (AnSb4) clusters.

PMID- 9910927
TI  - Multiple-pulse nuclear magnetic resonance of optically pumped xenon in a low
      magnetic field.

PMID- 9910929
TI  - Chirped adiabatic passage with temporally delayed pulses.

PMID- 9910928
TI  - Kramers-map approach for stabilization of a hydrogen atom in a monochromatic
      field.

PMID- 9910930
TI  - Effects of the phase of a laser field on autoionization.

PMID- 9910931
TI  - Velocity-selective optical pumping in four-wave mixing.

PMID- 9910932
TI  - Ramsey fringes in laser-assisted collisions.

PMID- 9910933
TI  - Ionization of the one-dimensional Coulomb atom in an intense laser field.

PMID- 9910934
TI  - Laser-induced modification of a structured continuum observed in ionization and
      harmonic generation.

PMID- 9910935
TI  - Origin of splits in Q functions for the Jaynes-Cummings model.

PMID- 9910936
TI  - Gain and noise in subthreshold longitudinal laser modes.

PMID- 9910937
TI  - Dark solitons generated by second-order parametric interactions.

PMID- 9910938
TI  - Intensity-intensity correlations for the micromaser: Spectral and antibunching
      characteristics.

PMID- 9910939
TI  - Dynamics of a monovelocity-atomic-beam maser framed in a semiclassical model.

PMID- 9910941
TI  - Propagation of partially polarized light.

PMID- 9910940
TI  - Doppler-free ultrafast modulation spectroscopy with phase-conjugation geometry.

PMID- 9910942
TI  - Method of integral equations and an extinction theorem for two-dimensional
      problems in nonlinear optics.

PMID- 9910943
TI  - Hopf bifurcation of the class-B multimode laser.

PMID- 9910944
TI  - Competition between geometrical and dynamical squeezing during a Franck-Condon
      transition.

PMID- 9910945
TI  - Emission spectra of a Lambda -type quantum-beat three-level atom.

PMID- 9910946
TI  - Lasing without inversion with a fluctuating pump: Gain dependence on pump noise
      and frequency.

PMID- 9910947
TI  - Quantum island states in the micromaser.

PMID- 9910948
TI  - Aspects of impulsive stimulated scattering in molecular systems.

PMID- 9910950
TI  - Statistics of photons and de-excited atoms in a micromaser with Poissonian
      pumping.

PMID- 9910949
TI  - "Classical" beat phenomena from the Jaynes-Cummings model with a Kerr
      nonlinearity.

PMID- 9910951
TI  - Eigenmodes of the dynamically coupled twin-stripe semiconductor laser.

PMID- 9910953
TI  - Hyperbolic phase and squeeze-parameter estimation.

PMID- 9910952
TI  - Noise reduction in the nondegenerate parametric oscillator with direct detection
      feedback.

PMID- 9910955
TI  - Multidimensional Hermite polynomials and photon distribution for polymode mixed
      light.

PMID- 9910954
TI  - Experimental study of the turn-on statistics of class-B lasers under the
      influence of additive noise.

PMID- 9910956
TI  - Rotation angle, phases of oscillators with definite circular polarizations, and
      the composite ideal phase operator.

PMID- 9910957
TI  - Mean-field approximation in semiconductor laser modeling.

PMID- 9910958
TI  - Correlated photon asymmetry in local realism.

PMID- 9910960
TI  - First ionization potential of tantalum by mass-selected double-resonance field
      ionization spectroscopy.

PMID- 9910959
TI  - Role of phase coherence in the transition dynamics of a periodically driven two
      level system.

PMID- 9910961
TI  - Variational equation of states of arbitrary angular momentum for two-particle
      systems.

PMID- 9910962
TI  - Ground-state energies for the helium isoelectronic series.

PMID- 9910963
TI  - Bounds to some local electron-pair properties with application to two-electron
      ions.

PMID- 9910964
TI  - Energy levels of a hydrogen atom in a magnetic field.

PMID- 9910965
TI  - Mean field for the vibron model: Dipole-moment function of diatomic molecules.

PMID- 9910966
TI  - Induced decay of composite JPC=1(+)+ particles in atomic Coulomb fields.

PMID- 9910967
TI  - Type-I intermittency in a four-level coherently pumped laser.

PMID- 9910968
TI  - Center-of-mass motion of an N-particle atom or ion and the Thomas-Reiche-Kuhn sum
      rule.

PMID- 9910970
TI  - Reality and measurement of the wave function.

PMID- 9910969
TI  - Geometric-phase effects in laser dynamics.

PMID- 9910971
TI  - Comment on "Generalized deformed oscillators for vibrational spectra of diatomic
      molecules"

PMID- 9910972
TI  - Reply to "Comment on 'Generalized deformed oscillators for vibrational spectra of
      diatomic molecules' "

PMID- 9910973
TI  - Erratum: Charge exchange between bare beryllium and boron with metastable
      hydrogen atoms at low energies

PMID- 9910974
TI  - Electron-impact ionization of the K shell of silver and gold in coplanar
      asymmetric geometry.

PMID- 9910975
TI  - Spin-1/2 particle and hole as supersymmetry partners.

PMID- 9910977
TI  - Observation of dihedral transverse patterning of Gaussian beams in nonlinear
      optics.

PMID- 9910976
TI  - Molecular-orientation effects in the dissociative ionization of CH4 in intense
      laser fields.

PMID- 9910979
TI  - Derivation of the energy-time uncertainty relation.

PMID- 9910978
TI  - Sum-frequency generation with a free-electron laser: A study of gallium
      phosphide.

PMID- 9910980
TI  - Models of particle detection in regions of space-time.

PMID- 9910981
TI  - Number-phase uncertainty product for displaced number states.

PMID- 9910982
TI  - Regularized semiclassical radial propagator for the Coulomb potential.

PMID- 9910983
TI  - Wave-function collapse and the quantum fluctuation-dissipation process.

PMID- 9910984
TI  - Using a Penning trap to weigh antiprotons.

PMID- 9910985
TI  - Moment-problem formulation of a minimax quantization procedure.

PMID- 9910986
TI  - Semiclassical propagation: Phase indices and the initial-value formalism.

PMID- 9910987
TI  - Photon-photon interaction in axial channeling.

PMID- 9910989
TI  - Wave function in the invariant representation and squeezed-state function of the
      time-dependent harmonic oscillator.

PMID- 9910988
TI  - Photon production by the dynamical Casimir effect.

PMID- 9910990
TI  - Supersymmetric quantum-mechanical approach to atomic closed shells in a bare
      Coulomb field.

PMID- 9910991
TI  - Eavesdropping on quantum-cryptographical systems.

PMID- 9910992
TI  - One-photon operators and the role of vacuum fluctuations in the Casimir force.

PMID- 9910993
TI  - Exclusion of intrinsically classical domains and the problem of quasiclassical
      emergence.

PMID- 9910994
TI  - Chaos-induced avoided level crossing and tunneling.

PMID- 9910995
TI  - Hyperfine structure and isotope-shift investigations of atomic nitrogen by
      saturation spectroscopy.

PMID- 9910997
TI  - Relative K x-ray intensities in some selected elements between Mn and Sb
      following ionization by 59.54-keV gamma rays.

PMID- 9910996
TI  - q-deformed vibron model for diatomic molecules.

PMID- 9910999
TI  - Electron affinities of opposite-parity bound states in Th-: Relativistic
      configuration-interaction studies.

PMID- 9910998
TI  - Measurement of atomic polarizabilities using Floquet spectroscopy.

PMID- 9911000
TI  - Isotope shift and hyperfine structure in the atomic spectrum of hafnium by laser
      spectroscopy.

PMID- 9911001
TI  - Ionization potentials and excitation energies of the alkali-metal atoms by the
      relativistic coupled-cluster method.

PMID- 9911002
TI  - Channel interference in resonance elastic x-ray scattering.

PMID- 9911003
TI  - Windowless, geometry-independent, phase-matched method for the measurement of the
      oscillator strengths of Xe, Kr, and Ar.

PMID- 9911004
TI  - Atomic cascade in muonic hydrogen and the problem of kinetic-energy distribution
      in the ground state.

PMID- 9911005
TI  - Electron affinities of six bound states of Ce- formed by attachment of 6p and 5d
      electrons to Ce.

PMID- 9911006
TI  - Translational energy spectra for single-electron capture by O2+ in He, Ne, and
      Ar.

PMID- 9911007
TI  - Relativistic many-body calculation of the electric dipole moment of atomic
      rubidium due to parity and time-reversal violation.

PMID- 9911008
TI  - Interaction-induced light scattering by gaseous methane: The bound dimer
      contribution (CH4)2.

PMID- 9911009
TI  - Cross sections of Nei+ recoil-ion production through pure ionization, electron
      loss, and electron capture of projectiles in 1.05-MeV/amu Arq++Ne collisions.

PMID- 9911010
TI  - Spin-polarized electron capture for the Na+3He2+ system at a 3He2+ impact energy
      of 5.33-9.33 keV/amu.

PMID- 9911011
TI  - Alignment of the 1s2p vacancy states of Ne doubly ionized by 700-2000-keV proton
      impact.

PMID- 9911012
TI  - Photoionization of two-electron atoms via the hyperspherical artificial-channel
      method: Application to H- and He.

PMID- 9911013
TI  - Argon 3s autoionization resonances.

PMID- 9911014
TI  - Interacting resonance effects along an isoelectronic sequence: Electron-impact
      excitation of Mg-like ions.

PMID- 9911015
TI  - Traversal-time wave-function analysis of resonance and nonresonance tunneling.

PMID- 9911017
TI  - Whole-atom integral incoherent scattering cross sections of elements Na, Cl, K,
      Cu, Br, Rb, Ag, Cd, I, and Hg at 661.6 keV.

PMID- 9911016
TI  - Absolute dielectronic recombination cross sections of hydrogenlike helium.

PMID- 9911018
TI  - High-resolution photoelectron spectrometry of atomic manganese from the region of
      the 3p-->3d giant resonance to 120 eV.

PMID- 9911019
TI  - Photoelectron angular distribution asymmetry parameters in H- photodetachment
      below the N=3 threshold.

PMID- 9911020
TI  - Energy-pooling collisions in barium.

PMID- 9911022
TI  - Screening effects in pair production by 10-MeV photons on uranium atoms.

PMID- 9911021
TI  - First-order theories for adiabatic L-shell ionization by protons.

PMID- 9911023
TI  - Relativistic, retardation, and multipole effects in photoionization cross
      sections: Z, n, and l dependence.

PMID- 9911024
TI  - Mechanism of the enhancement of some high-lying resonance series in the
      photoionization spectra of excited helium.

PMID- 9911025
TI  - Angular distribution of delta electrons emitted in collisions of 1.0-MeV/u Fq+
      (q=4,6,8,9) with molecular hydrogen.

PMID- 9911026
TI  - Exchange and fine-structure effects in autoionization of large-angular-momentum
      doubly excited Rydberg states.

PMID- 9911027
TI  - Time-dependent approach to atomic autoionization.

PMID- 9911029
TI  - Probability for K- and L-vacancy creation in electron-capture decay.

PMID- 9911028
TI  - Threshold K-LL Auger spectra of P in InP.

PMID- 9911031
TI  - Low-energy electron-collision processes in molecular chlorine.

PMID- 9911030
TI  - Absolute cross-section measurements for electron-impact single ionization of Si4+
      and Si5+

PMID- 9911032
TI  - Retardation and multipole effects in Rayleigh scattering by hydrogenlike ions at
      low and x-ray photon energies.

PMID- 9911033
TI  - Wavelength dependence of the absolute Na2+(1 (2) Sigma u+<--1 (2) Sigma g+)
      photodissociation cross section.

PMID- 9911034
TI  - Nonadiabatic effects in two-level systems: A classical analysis.

PMID- 9911035
TI  - Regge-pole description of rainbow scattering by means of the phase-integral
      method.

PMID- 9911036
TI  - Angular distribution of K Auger electrons ejected by highly charged ions
      interacting with an Al(111) surface.

PMID- 9911037
TI  - Charge-state equilibration length of a highly charged ion inside a carbon solid.

PMID- 9911038
TI  - Fragmentation of atomic clusters: A theoretical study.

PMID- 9911039
TI  - Size dependence of electronic structure and adiabatic type of collective
      vibration in small metal clusters.

PMID- 9911040
TI  - Bremsstrahlung near reaction thresholds.

PMID- 9911041
TI  - Optical resonance and coherent transients in dressed atomic systems.

PMID- 9911042
TI  - Heating due to long-range photon exchange interactions between cold atoms.

PMID- 9911043
TI  - Spontaneous emission in a cavity driven by a strong bichromatic field.

PMID- 9911044
TI  - Sub-Doppler cooling of three-level Lambda atoms in space-shifted standing light
      waves.

PMID- 9911045
TI  - Cold collisions in a laser field: Quantum Monte Carlo treatment of radiative
      heating.

PMID- 9911046
TI  - Forward-scattering ring structure and the spectra dependence on laser frequency.

PMID- 9911047
TI  - Modeling harmonic generation by a zero-range potential.

PMID- 9911048
TI  - Analysis of atomic mirrors based on light-induced forces.

PMID- 9911049
TI  - Transition probability in the Ramsey method with arbitrary initial and final
      frequencies of separated oscillatory fields.

PMID- 9911050
TI  - Ionization of Rydberg atoms by an electric-field kick.

PMID- 9911052
TI  - Selective reflection from a vapor of three-level atoms.

PMID- 9911051
TI  - Influence of specularly reflecting boundaries on radiation trapping in a plane
      parallel slab.

PMID- 9911053
TI  - Multiphoton ionization of magnesium via an autoionizing state.

PMID- 9911054
TI  - Landau-Zener treatment of intensity-tuned multiphoton resonances of potassium.

PMID- 9911055
TI  - Autoionizing states of negative ions in strong resonant laser fields: The
      negative rubidium ion.

PMID- 9911056
TI  - Spectral analysis of the degenerate optical parametric oscillator as a noiseless
      amplifier.

PMID- 9911057
TI  - Weak turbulent behavior and dynamical frequency locking in a high-Fresnel-number
      laser.

PMID- 9911058
TI  - Influence of correlated stochastic perturbations on the nonlinear optical
      properties of a dimer.

PMID- 9911059
TI  - Definition of a laser threshold.

PMID- 9911060
TI  - Nonlinear atom optics: General formalism and atomic solitons.

PMID- 9911061
TI  - Stochastic fluctuations in the Jaynes-Cummings model.

PMID- 9911062
TI  - Photon-statistics dependence of single-atom absorption.

PMID- 9911063
TI  - Saturation effects in a two-mode ring laser.

PMID- 9911064
TI  - Exponential gain and self-bunching in a collective atomic recoil laser.

PMID- 9911065
TI  - Annihilation operators and coherent states for the Jaynes-Cummings model.

PMID- 9911066
TI  - Nonlinear dynamics of dual-frequency-pumped multiwave mixing in optical fibers.

PMID- 9911067
TI  - Nonadiabatic linewidth of a Lambda -type noninversion laser.

PMID- 9911068
TI  - Spontaneous excitation of an accelerated atom: The contributions of vacuum
      fluctuations and radiation reaction.

PMID- 9911069
TI  - Spontaneous emission near the edge of a photonic band gap.

PMID- 9911070
TI  - Competing three-photon and one-photon transitions in cavity quantum
      electrodynamics.

PMID- 9911071
TI  - Vibrational Schrodinger-cat states.

PMID- 9911072
TI  - Properties of a deformed Jaynes-Cummings model.

PMID- 9911073
TI  - Driving atoms with light of arbitrary statistics.

PMID- 9911074
TI  - Conservation law for multiple four-wave-mixing processes in a nonlinear optical
      medium.

PMID- 9911075
TI  - Photon amplification in a two-photon lossless micromaser.

PMID- 9911076
TI  - Minimal model of a class-B laser with delayed feedback: Cascading branching of
      periodic solutions and period-doubling bifurcation.

PMID- 9911077
TI  - Quantization of electromagnetic fields in cavities and spontaneous emission.

PMID- 9911078
TI  - Periodically loss-modulated CO2 laser as an optical amplitude and phase
      multitrigger.

PMID- 9911079
TI  - Stabilization in relativistic photoionization with circularly polarized light.

PMID- 9911080
TI  - Bright spatial soliton dynamics in a symmetric optical planar waveguide
      structure.

PMID- 9911081
TI  - Enhanced transient squeezing in a kicked Jaynes-Cummings model.

PMID- 9911082
TI  - Quantum noise reduction close to an optically bistable dark resonance.

PMID- 9911084
TI  - Excess noise correlation using population-trapped atoms.

PMID- 9911083
TI  - Experimental and theoretical investigation of neonlike selenium x-ray laser
      spectral linewidths and their variation with amplification.

PMID- 9911085
TI  - Rotation-operator approach and spin dynamics in a time-varying magnetic field.

PMID- 9911086
TI  - Direct and real-time holographic monitoring of relative changes in two random
      rough surfaces.

PMID- 9911087
TI  - Connection of a type of q-deformed binomial state with q-spin coherent states.

PMID- 9911089
TI  - Theoretical complex Stark energies of hydrogen by a complex-scaling plus B-spline
      approach.

PMID- 9911088
TI  - Quantum limits for measurements on macroscopic bodies: A decoherence analysis.

PMID- 9911090
TI  - Laser-rf double-resonance spectroscopy of refractory elements: 183W I and 181Ta
      I.

PMID- 9911091
TI  - Resonances in e--Ps elastic scattering via a direct solution of the three-body
      scattering problem.

PMID- 9911092
TI  - Asymptotic calculation of the exchange interaction between two long-range
      interacting atoms with open valence shells of any type.

PMID- 9911093
TI  - Ion-atom charge-transfer system for a heavy-ion-beam pumped laser.

PMID- 9911095
TI  - Pure-state generation via dispersion forces in a cooperative system.

PMID- 9911094
TI  - Radiation amplification near an autoionizing state: A model in atomic Ca.

PMID- 9911097
TI  - Saturation of harmonic generation in one- and three-dimensional atoms.

PMID- 9911096
TI  - Photon statistics of multimode even and odd coherent light.

PMID- 9911098
TI  - Two-photon squeezed laser with long-lived atoms.

PMID- 9911099
TI  - Comment on "Asymmetry of the Aharonov-Bohm diffraction pattern and Ehrenfest's
      theorem"

PMID- 9911100
TI  - Reply to "Comment on 'Asymmetry of the Aharonov-Bohm diffraction pattern and
      Ehrenfest's theorem' "

PMID- 9911102
TI  - Observation of collisionally induced (1s2p2p')4Pe shape resonance of He-

PMID- 9911101
TI  - Teleportation of an atomic state between two cavities using nonlocal microwave
      fields.

PMID- 9911103
TI  - Laser turn-on effects and proper field description in laser-atom interactions.

PMID- 9911105
TI  - Approximation for a Coulomb-Volkov solution in strong fields.

PMID- 9911104
TI  - Laser-induced ultracold Rb(5S1/2)+Rb(5P1/2) collisions.

PMID- 9911107
TI  - Self-induced planar and cylindrical splitting of a laser beam in sodium vapor.

PMID- 9911106
TI  - Population transfer through the continuum.

PMID- 9911108
TI  - Phase retrieval in quantum mechanics.

PMID- 9911110
TI  - Amplification of vacuum fluctuations by two-beam coupling in atomic vapors.

PMID- 9911109
TI  - Atomic-beam and cavity-field correlation functions in the micromaser.

PMID- 9911111
TI  - Possibility of verifying the superposition law of angular velocities by means of
      electro-optics.

PMID- 9911112
TI  - Quantum dynamics in dual spaces.

PMID- 9911113
TI  - Scaling of localization lengths in quantum dynamics.

PMID- 9911114
TI  - Quasiclassical approximation for the spin-boson Hamiltonian with counterrotating
      terms.

PMID- 9911116
TI  - Computation of tunneling rates in time-dependent electric fields: Electrons on
      the surface of liquid helium, a one-dimensional hydrogen atom.

PMID- 9911115
TI  - Supersymmetry of a relativistic electron in a uniform magnetic field.

PMID- 9911117
TI  - Transition radiation and Bragg resonances.

PMID- 9911119
TI  - Ramsey fringes in atomic interferometry: Measurability of the influence of space
      time curvature.

PMID- 9911118
TI  - Numerical tests of the Lande subtraction method for the Coulomb potential in
      momentum space.

PMID- 9911121
TI  - How interference effects in mixtures determine the rules of quantum mechanics.

PMID- 9911120
TI  - Application of the coupled-cluster approach to the electric dipole moment of
      atoms and molecules due to parity and time-reversal violation.

PMID- 9911123
TI  - From electron densities to Kohn-Sham kinetic energies, orbital energies, exchange
      correlation potentials, and exchange-correlation energies.

PMID- 9911122
TI  - Correspondence rules in macroscopic quantum electrodynamics.

PMID- 9911125
TI  - Measurements of the ground-state Lamb shift and electron-correlation effects in
      hydrogenlike and heliumlike uranium.

PMID- 9911124
TI  - Measurement of the Ly- alpha Mg resonance with the 2s-->3p Ne-like Ge line.

PMID- 9911127
TI  - Laser spectroscopy of the HgCd exciplex.

PMID- 9911126
TI  - 1,3Do resonant states in Ps-

PMID- 9911128
TI  - Precision lifetime measurements of Cs 6p 2P1/2 and 6p 2P3/2 levels by single
      photon counting.

PMID- 9911129
TI  - Effects of quantum-mechanical symmetry on electronic correlations in intrashell
      states of four-valence-electron atoms.

PMID- 9911130
TI  - Positron binding: A positron-density viewpoint.

PMID- 9911131
TI  - Measurement of the lifetime of the 2 (3)P2 state in heliumlike krypton using a
      two-foil target.

PMID- 9911133
TI  - Quantum field theory of atoms interacting with photons: Foundations.

PMID- 9911132
TI  - Localization of electron momentum in atomic and molecular systems.

PMID- 9911134
TI  - Two-center overlap integrals over Slater-type orbitals constrained to a spherical
      integration volume: Analytical expressions.

PMID- 9911135
TI  - Generalized effective-core-potential method: Potentials for the atoms Xe, Pd, and
      Ag.

PMID- 9911136
TI  - Soft x-ray emission of galliumlike rare-earth atoms produced by high-temperature
      low-density tokamak and high-density laser plasmas.

PMID- 9911137
TI  - Reexamination of the He- 1s2p2 4Pe shape resonance: Details of its properties and
      a precise electron affinity for He 2 (3)S.

PMID- 9911138
TI  - Velocity dependence of captured-electron l distributions in low-energy collisions
      of Ar8+ with atomic Cs.

PMID- 9911139
TI  - Angular correlation and differential cross sections in e--H(1 (2)S-3 (2)P)
      excitation.

PMID- 9911140
TI  - Orientation effects in charge exchange: Probing short-range repulsion by
      interference patterns.

PMID- 9911141
TI  - Relativistic effects on angular distribution of Auger electrons emitted from Be
      like ions following electron-impact excitation.

PMID- 9911142
TI  - Semiclassical approach to Rydberg-atom intercombination transitions in collisions
      with electrons.

PMID- 9911143
TI  - Superelastic and inelastic He2++He state-selective electron capture.

PMID- 9911144
TI  - Observation of anisotropic angular distribution of ionic fragments in the
      dissociation of CO2+

PMID- 9911145
TI  - Rotational and vibrational lifetime of isotopically asymmetrized homonuclear
      diatomic molecular ions.

PMID- 9911146
TI  - Electron-energy spectra of H- doubly excited states resulting from collisions of
      H- with He.

PMID- 9911147
TI  - Electron-positron pair production in Coulomb collisions by 6.4-TeV sulfur ions.

PMID- 9911149
TI  - Direct numerical approach to electron-hydrogen scattering. II. L>0.

PMID- 9911148
TI  - True double capture in collisions of bare and hydrogenlike ions with rare-gas
      atoms (Z=7-13).

PMID- 9911150
TI  - Temporal evolution of the vibrational excitation within the 1 Sigma g+ state of
      N2 in the positive column of a pulsed electric discharge.

PMID- 9911152
TI  - Influence of the initial- and final-state configuration interaction on the
      anisotropy of the resonant Auger decay of Kr 3d-15p and Xe 4d-16p states.

PMID- 9911151
TI  - General properties of the spectrum of complex scaled Hamiltonians:
      Phenomenological description of pole string curves.

PMID- 9911153
TI  - Semiclassical three-charged-particle system in the framework of the Pechukas self
      consistent method.

PMID- 9911154
TI  - Electronic excitation of H2 in slow collisions with molecular ions.

PMID- 9911155
TI  - Theoretical description of the ejected-electron spectrum in collisions of 1.5
      MeV/u F9+ with helium.

PMID- 9911156
TI  - Additivity studies of the stopping powers of eleven halogenated hydrocarbons for
      protons and alpha particles.

PMID- 9911157
TI  - Energy loss of carbon-transmitted 1-MeV H2+ ions.

PMID- 9911158
TI  - Quantum formalism for electron capture from a solid surface by heavy projectiles
      making grazing collisions.

PMID- 9911159
TI  - Bound-electron capture from surface atoms by heavy projectiles at grazing
      collisions.

PMID- 9911160
TI  - "Heisenberg microscope" decoherence atom interferometry.

PMID- 9911162
TI  - Atom manipulation based on delayed laser pulses in three- and four-level systems:
      Light shifts and transfer efficiencies.

PMID- 9911163
TI  - Oscillatory dynamics in light-induced drift.

PMID- 9911161
TI  - Large frequency shifts of absorption profiles due to the combination of optical
      pumping, light shift, and magnetic fields in sodium vapor.

PMID- 9911164
TI  - High-density production of spin-polarized atomic hydrogen and deuterium.

PMID- 9911165
TI  - Multiphoton processes in the velocity gauge.

PMID- 9911166
TI  - Atomic barium and cesium alignment-to-orientation conversion in external electric
      and magnetic fields.

PMID- 9911167
TI  - Rydberg-atom stabilization against photoionization: An analytically solvable
      model with resonance.

PMID- 9911168
TI  - Relaxation, generation, and detection of Zeeman coherences in an optically pumped
      heavy-alkali-metal vapor.

PMID- 9911170
TI  - Partial and total multiphoton detachment rates for H- in a perturbative B-spline
      based approach.

PMID- 9911169
TI  - Short-pulse microwave ionization of Na Rydberg atoms.

PMID- 9911171
TI  - Stimulated magneto-optical force in the dressed-atom picture.

PMID- 9911172
TI  - Ionization of an excited hydrogen atom by a high-frequency circularly polarized
      pulsed field.

PMID- 9911173
TI  - Locking a molecular bond: A case study of CsI.

PMID- 9911174
TI  - Evolution of quantum superpositions in open environments: Quantum trajectories,
      jumps, and localization in phase space.

PMID- 9911176
TI  - Coexistence of attractors in a laser diode with optical feedback from a large
      external cavity.

PMID- 9911175
TI  - Observation of quantum beating in a simple beam-splitting experiment: Two
      particle entanglement in spin and space-time.

PMID- 9911178
TI  - Mode structure and the noise performance of a gain-guided amplifier.

PMID- 9911177
TI  - Optical second-harmonic generation at total reflection in a potassium dihydrogen
      phosphate crystal.

PMID- 9911179
TI  - Steady-state squeezing in a driven three-level Lambda system.

PMID- 9911180
TI  - Electromagnetic-field-induced quenching of the effects of noisy lasers.

PMID- 9911181
TI  - Non-Abelian gauge symmetry and the Jaynes-Cummings model.

PMID- 9911182
TI  - Effective nonlinear susceptibilities in the quantum theory of parametric down
      conversion.

PMID- 9911183
TI  - Exchange effects on cooperative radiation interaction in a two-atom model.

PMID- 9911185
TI  - Many-body quantum Monte Carlo wave-function approach to the dissipative atom
      field interaction.

PMID- 9911184
TI  - Dynamical restrictions to squeezing in a degenerate optical parametric
      oscillator.

PMID- 9911186
TI  - Optimum field squeezing from atomic sources: Three-level atoms.

PMID- 9911187
TI  - Quantum-optical master equations: An interaction picture.

PMID- 9911188
TI  - Coherent atomic waveguides from hollow optical fibers: Quantized atomic motion.

PMID- 9911189
TI  - Electron distribution function in a thin plasma layer and possible x-ray laser
      emission due to a sharp temperature gradient.

PMID- 9911190
TI  - Radiation in spherically symmetric structures. I. The coupled-amplitude equations
      for vector spherical waves.

PMID- 9911192
TI  - Antimode dynamics and chaotic itinerancy in the coherence collapse of
      semiconductor lasers with optical feedback.

PMID- 9911191
TI  - Radiation in spherically symmetric structures. II. Enhancement and inhibition of
      dipole radiation in a spherical Bragg cavity.

PMID- 9911193
TI  - Antinormal ordering of Susskind-Glogower quantum phase operators.

PMID- 9911195
TI  - Preferred basis in a measurement process.

PMID- 9911194
TI  - Stark shift of a single barium ion and potential application to zero-point
      confinement in a rf trap.

PMID- 9911197
TI  - High-resolution photoabsorption measurement and multichannel quantum-defect
      theory analysis of the 2p53s(1P1) ns,nd autoionizing series of sodium.

PMID- 9911196
TI  - Generalized antinormally ordered quantum phase-space distribution functions.

PMID- 9911199
TI  - Beam-laser lifetime measurements of Yb II energy levels.

PMID- 9911198
TI  - Weak capture of negative muons in hydrogenic media.

PMID- 9911200
TI  - Effect of noise on the tunneling through a potential barrier.

PMID- 9911202
TI  - Quantum states for a Paul-trapped particle in an intense laser field.

PMID- 9911201
TI  - Stabilization theory for computing energies and widths of resonances.

PMID- 9911203
TI  - Floquet eigenstates of an atom in an ultrastrong laser field.

PMID- 9911204
TI  - Relation between the N-atom laser and the one-atom laser.

PMID- 9911206
TI  - Generalized coherent state for multimode bosonic realization of the su(2) Lie
      algebra.

PMID- 9911205
TI  - Effect of the continuum on electromagnetically induced transparency with matched
      pulses.

PMID- 9911207
TI  - Unitary equivalence between ideal and feasible phases.

PMID- 9911208
TI  - Comment on "Meaning of the wave function"

PMID- 9911209
TI  - Erratum: Self-consistent frequencies of the electron-photon system

PMID- 9911210
TI  - Charge transfer in ion collisions with circular Rydberg atoms.

PMID- 9911211
TI  - Mechanics of particles with nonmonotonic dispersion laws.

PMID- 9911212
TI  - Possibility that Schrodinger's conjecture for the hydrogen-atom coherent states
      is not attainable.

PMID- 9911213
TI  - Precision lifetime measurements of the 6p2P1/2,3/2 states in atomic cesium.

PMID- 9911214
TI  - High-precision calculations of the Zeeman effect in the 2 3PJ, 2 1P1, 2 3S1, and
      3 3PJ states of helium.

PMID- 9911215
TI  - Field-assisted photodetachment process to observe the ponderomotive shift.

PMID- 9911216
TI  - Second-sideband laser cooling and nonclassical motion of trapped ions.

PMID- 9911218
TI  - Phase squeezing in a three-level atom micromaser.

PMID- 9911217
TI  - Method for velocimetry of cold atoms.

PMID- 9911220
TI  - Secular perturbation theory of long-range interactions.

PMID- 9911219
TI  - Four-wave mixing in optically dense media.

PMID- 9911221
TI  - Early-time properties of quantum evolution.

PMID- 9911222
TI  - Inadequacy of Ehrenfest's theorem to characterize the classical regime.

PMID- 9911223
TI  - Neutron acceleration in uniform electromagnetic fields.

PMID- 9911225
TI  - Einstein-Podolsky-Rosen paradox for continuous variables using radiation fields
      in the pair-coherent state.

PMID- 9911224
TI  - Even and odd two-photon coherent states of the radiation field.

PMID- 9911227
TI  - Phase statistics and phase-space measurements.

PMID- 9911226
TI  - Spectral inheritance of potentials with flat bottoms.

PMID- 9911228
TI  - Limiting analytic form for an Aharonov-Bohm diffraction pattern.

PMID- 9911230
TI  - Nonrelativistic theory of the radiation reaction interaction.

PMID- 9911229
TI  - Multichannel quantum mechanics as a Hamiltonian phase flow.

PMID- 9911232
TI  - so(2,1) Lie algebra and the Green's functions for the conditionally exactly
      solvable potentials.

PMID- 9911231
TI  - Large correlation effects of small perturbations by preselection and
      postselection of states.

PMID- 9911233
TI  - Symplectic transformations in the n-mode coherent-state representation using
      integration within an ordered product of operators.

PMID- 9911234
TI  - Ground-state energies of hydrogenic atoms in a uniform magnetic field of
      arbitrary strength.

PMID- 9911235
TI  - Predissociation quantum yields of singlet nitrogen.

PMID- 9911236
TI  - Spline-Galerkin methods applied to Rydberg series between the 4s 2S and 3d 2D
      limits of calcium.

PMID- 9911237
TI  - Static hyperpolarizability of atomic lithium.

PMID- 9911238
TI  - Corrections to the Born-Oppenheimer approximation by means of perturbation
      theory.

PMID- 9911239
TI  - Improved experimental limit on the electric dipole moment of the electron.

PMID- 9911240
TI  - Measurement of the C 3 Pi u radiative lifetime of N2 by laser-induced
      fluorescence.

PMID- 9911241
TI  - Electron-impact collision strengths for neutral fluorine.

PMID- 9911242
TI  - Numerical Liouville approach: A calculation method for nonlinear optical
      susceptibilities of N-state systems.

PMID- 9911243
TI  - Influence of relaxation phenomena in the unified description of resonant and
      nonresonant radiative transitions.

PMID- 9911244
TI  - Calculation of the Bethe logarithm for the Rydberg states of helium.

PMID- 9911246
TI  - Forbidden 2s1/2-1s1/2 radiative atomic transition.

PMID- 9911245
TI  - Quadratic Zeeman effect in hydrogen Rydberg states: Rigorous error estimates for
      energy eigenvalues, energy eigenfunctions, and oscillator strengths.

PMID- 9911247
TI  - Position and momentum information entropies of the D-dimensional harmonic
      oscillator and hydrogen atom.

PMID- 9911248
TI  - Large-scale multiconfiguration Hartree-Fock and configuration-interaction
      calculations of isotope shifts and hyperfine structures in boron.

PMID- 9911249
TI  - Magnetic-field density-functional theory.

PMID- 9911251
TI  - Electron-impact excitation along an isoelectronic sequence: B-like ions.

PMID- 9911250
TI  - Long-range potentials, including retardation, for the interaction of two alkali
      metal atoms.

PMID- 9911252
TI  - Auger electron emission following double electron capture in 150-keV Ne10++He
      collisions.

PMID- 9911254
TI  - Threshold effects in positron scattering on noble gases.

PMID- 9911253
TI  - Inelastic electron-dipole-molecule scattering at sub-milli-electron-volt
      energies: Possible role of dipole-supported states.

PMID- 9911255
TI  - Dielectronic recombination versus charge exchange: Electron capture by metastable
      ions.

PMID- 9911256
TI  - Isolation of the regions of potential significance in fine-structure transitions
      using adiabatic and functional sensitivity analyses: A comparative investigation
      with application to Na(2P1/2)+He-->Na(2P3/2)+He and Na(2P1/2)+Ar-->Na(2P3/2)+Ar.

PMID- 9911257
TI  - Quenching collisions of low-energy metastable multiply charged argon ions.

PMID- 9911259
TI  - Dissociative ionization of H2, N2, and O2 by electron impact.

PMID- 9911258
TI  - Photoionization of the 2p subshell of sodium atoms in ground and excited states.

PMID- 9911260
TI  - Photoexcitation and -ionization in helium: Zero-kinetic-energy spectroscopy.

PMID- 9911261
TI  - Computation of the scattering length and effective range in molecular physics.

PMID- 9911262
TI  - Dissociative cross sections of H2 by electron impact.

PMID- 9911263
TI  - Relationship between the Born and impulse approximations for the antiscreening
      process.

PMID- 9911264
TI  - Stopping power for hydrogen molecular ions in solids: Influence of the inner
      shell electrons of target atoms.

PMID- 9911265
TI  - Analysis of charge-dependent stopping of swift ions.

PMID- 9911266
TI  - Semiclassical formalism in ion-surface capture at high energies.

PMID- 9911267
TI  - Multiphoton detachment of H-. II. Intensity-dependent photodetachment rates and
      threshold behavior-complex-scaling generalized pseudospectral method.

PMID- 9911269
TI  - Converged three-dimensional calculations of above-threshold ionization: Angular
      momentum constraints and the kinetic-energy distribution.

PMID- 9911268
TI  - Steric effects in multiphoton excitation.

PMID- 9911270
TI  - Ionization of He by ultrastrong single-cycle pulses.

PMID- 9911271
TI  - Threshold and Coulomb effects in multiphoton ionization.

PMID- 9911272
TI  - Correlated Keldysh-Faisal-Reiss theory of above-threshold double ionization of He
      in intense laser fields.

PMID- 9911273
TI  - Atomic motion in a magneto-optical field.

PMID- 9911274
TI  - Application of the scrL2 box-stabilization method to time-periodic systems.

PMID- 9911275
TI  - Multilevel light-induced continuum structure: Strong-probe and stabilization
      effects.

PMID- 9911276
TI  - Gaussian noise and quantum-optical communication.

PMID- 9911277
TI  - Non-Markovian analysis of coherence in a driven two-level atom.

PMID- 9911278
TI  - Accumulated photon echoes generated by synchrotron radiation.

PMID- 9911279
TI  - Electron-beam-induced super-radiant emission from a grating.

PMID- 9911280
TI  - Complexity of dynamical bifurcations in detuned degenerate four-wave mixing.

PMID- 9911281
TI  - Thermal coherent states in the Bargmann representation.

PMID- 9911282
TI  - Single-atom interference method for generating Fock states.

PMID- 9911283
TI  - Enhancement of degenerate four-wave mixing by atom-wall collisions in atomic
      vapors.

PMID- 9911284
TI  - Spatiotemporal coherence properties of entangled light beams generated by
      parametric down-conversion.

PMID- 9911285
TI  - Pump-induced transparency and enhanced third-harmonic generation near an
      autoionizing state.

PMID- 9911286
TI  - Spatial distortions of laser pulses in coherent on-resonance propagation: Large
      scale self-focusing.

PMID- 9911287
TI  - Forced indistinguishability in "induced coherence without stimulated emission"

PMID- 9911288
TI  - Dense configuration of solitons in resonant four-wave mixing.

PMID- 9911289
TI  - Inversionless gain in driven three-level ssV-type atoms: A comparison of
      broadband and monochromatic excitation.

PMID- 9911290
TI  - Dynamical ordering: Applications to Fokker-Planck equations.

PMID- 9911291
TI  - Quantum dynamics of a laser-cooled ideal gas.

PMID- 9911293
TI  - Normal-form theory for a laser model with periodic signal and noise injection.

PMID- 9911292
TI  - Coherent states in a finite-dimensional Hilbert space.

PMID- 9911294
TI  - Generation and propagation of high-order harmonics in a rapidly ionizing medium.

PMID- 9911295
TI  - Approximate model for optical pulse compression by cross-phase modulation in
      Bragg gratings.

PMID- 9911296
TI  - Nonperturbative studies of a quantum higher-order nonlinear Schrodinger model
      using the Bethe ansatz.

PMID- 9911298
TI  - Hexagons and squares in a passive nonlinear optical system.

PMID- 9911297
TI  - Chaotic and periodic passive Q switching in coupled CO2 lasers with a saturable
      absorber.

PMID- 9911299
TI  - Spin-correlated interferometry for polarized and unpolarized photons on a beam
      splitter.

PMID- 9911300
TI  - Fundamental limit on energy transfer in k-photon down-conversion.

PMID- 9911301
TI  - Complete atomic population inversion using correlated sidebands.

PMID- 9911302
TI  - Phase-state representation in quantum optics.

PMID- 9911303
TI  - Universal function and its application to the 2p-3s transition in sodium.

PMID- 9911305
TI  - Spurious solutions arising in matrix approximations to the Dirac-Coulomb problem.

PMID- 9911304
TI  - Convergence of the hyperspherical-harmonic expansion for two-electron atoms.

PMID- 9911306
TI  - Equations satisfied by the kinetic-energy functional and its derivatives.

PMID- 9911308
TI  - Stopping power of carbon for 9.6-MeV/amu H2+ ions.

PMID- 9911307
TI  - Collective response and molecular effects in cluster photoionization: A one
      center time-dependent calculation for BaO2.

PMID- 9911309
TI  - Deviation from the Fano profile in resonance-enhanced multiphoton autoionization.

PMID- 9911311
TI  - Jaynes-Cummings model with a para-Bose oscillator.

PMID- 9911310
TI  - Electro-optic measurement of the electric-field distributions in coplanar
      electrode poled polymers.

PMID- 9911312
TI  - Comment on "Squeezing and antisqueezing for a harmonic oscillator having a sudden
      change of mass"

PMID- 9911313
TI  - Erratum: Correlation-potential method for negative ions and electron scattering

PMID- 9911314
TI  - Erratum: Z scaling of the 3P-3S Li isoelectronic series transition: Quadrupole
      Stark broadening and resonances

PMID- 9911315
TI  - Preparation of macroscopic superpositions in many-atom systems.

PMID- 9911316
TI  - Reliability of Bell-inequality measurements using polarization correlations in
      parametric-down-conversion photon sources.

PMID- 9911318
TI  - Excitation-ionization and double ionization of helium by Compton scattering.

PMID- 9911317
TI  - Direct dissociative recombination of ground-state HeH+

PMID- 9911319
TI  - Density of states for complex molecules.

PMID- 9911321
TI  - Settling a long-standing question on strong-field double ionization.

PMID- 9911320
TI  - Calculation of triple-differential cross sections in electron scattering on
      atomic hydrogen.

PMID- 9911322
TI  - Loss from magneto-optical traps in strong laser fields.

PMID- 9911324
TI  - Generation of short-pulse tunable xuv radiation by high-order frequency mixing.

PMID- 9911323
TI  - Effects of resonant dipole interaction between atoms on laser cooling: The case
      of two identical atoms.

PMID- 9911325
TI  - Nonlocal potential for class-B lasers with external optical feedback.

PMID- 9911326
TI  - Exact numerical solution of the spinless Salpeter equation for the Coulomb
      potential in momentum space.

PMID- 9911327
TI  - Quantum theory of radiation pressure on a dielectric slab.

PMID- 9911328
TI  - Nonlocal approach to scattering in a one-dimensional problem.

PMID- 9911329
TI  - Quasiclassical path-integral approach to supersymmetric quantum mechanics.

PMID- 9911330
TI  - Stochastic wave-function approach to non-Markovian systems.

PMID- 9911331
TI  - Semiclassical multicomponent wave function.

PMID- 9911333
TI  - Fundamental limits upon the measurement of state vectors.

PMID- 9911332
TI  - Multiparticle and higher-spin tests of quantum mechanics using parametric down
      conversion.

PMID- 9911334
TI  - Deformed oscillator algebras for two-dimensional quantum superintegrable systems.

PMID- 9911336
TI  - Laser spectroscopy of some HgCd spin-orbit states.

PMID- 9911335
TI  - Statistics and characteristics of xuv transition arrays from laser-produced
      plasmas of the elements tin through iodine.

PMID- 9911337
TI  - n=5 to n=5 soft-x-ray emission of uranium in a high-temperature low-density
      tokamak plasma.

PMID- 9911338
TI  - Radiation trapping in phase-modulation fluorometry.

PMID- 9911339
TI  - Transfer of electron correlation from an electron gas to inhomogeneous systems
      via Jastrow factors.

PMID- 9911341
TI  - Density matrix for a triatomic linear molecule model.

PMID- 9911340
TI  - Configuration-interaction study of the differential correlation energies among
      the lowest 2S, 2D, and 2Po states of Ca+

PMID- 9911343
TI  - Gradient-free exchange-correlation functional beyond the local-spin-density
      approximation.

PMID- 9911342
TI  - Time-dependent functional theory of coupled electron and electromagnetic fields
      in condensed-matter systems.

PMID- 9911344
TI  - Influence of a strong magnetic field on the chemical bond of the excited H2+ ion.

PMID- 9911346
TI  - Dynamics of hydrogenic wave packets in electric and magnetic fields.

PMID- 9911345
TI  - Electron correlation, geometry, and energy spectrum of quadruply excited states.

PMID- 9911348
TI  - High-precision calculation of the isotope shift in the ratio gJ(3He, 2
      (3)S1)/gJ(4He, 2 (3)S1).

PMID- 9911347
TI  - One- and two-electron excitations of helium in the s-wave model.

PMID- 9911350
TI  - Energies and fine structures of 1s22snp (n=2,3) 1Po and 3P2,1,0o states of Be
      like ions.

PMID- 9911349
TI  - Calculation of the weak interactions in dysprosium.

PMID- 9911351
TI  - Accurate exchange-correlation potentials and total-energy components for the
      helium isoelectronic series.

PMID- 9911352
TI  - Upper and lower bounds on the energy eigenvalues of the one-electron Dirac
      Hamiltonian.

PMID- 9911353
TI  - Retardation (or Casimir) potential for the Rydberg hydrogen molecule.

PMID- 9911354
TI  - Center-of-mass energy distributions of coincident H- and H+ from the collision
      induced dissociation of H3+ in He.

PMID- 9911355
TI  - Cross section for the photodetachment of Be-

PMID- 9911356
TI  - Relativistic distorted-wave Born calculations for (e,2e) processes on inner
      shells of heavy atoms.

PMID- 9911358
TI  - Single- and double-photoionization cross sections of carbon dioxide (CO2) and
      ionic fragmentation of CO2+ and CO22+

PMID- 9911357
TI  - Investigation of complex ionization amplitudes in cadmium by (e,2e) spectroscopy.

PMID- 9911359
TI  - Screening effects for transition probabilities in collisions of charged particles
      with an atom or stripped ion.

PMID- 9911360
TI  - Convergence of the multipole expansion for the doubly differential ionization
      cross section.

PMID- 9911361
TI  - Small-angle electron differential cross sections for the Na 3s-3p transition:
      Accuracy of measurements.

PMID- 9911363
TI  - Excitation of the 3PJ=0,1,2 fine-structure levels of atomic oxygen in collisions
      with oxygen atoms.

PMID- 9911364
TI  - Zero-point energy differences and many-body dispersion forces.

PMID- 9911362
TI  - Satellites and resonant satellites in the photoionization of atomic Cu.

PMID- 9911365
TI  - Ionization and charge transfer of atomic hydrogen in collision with multiply
      charged ions.

PMID- 9911366
TI  - Transparency of one-channel and multichannel quantum systems.

PMID- 9911368
TI  - Photoabsorption cross section of O, S, Se, and Te.

PMID- 9911367
TI  - Binary-encounter-dipole model for electron-impact ionization.

PMID- 9911370
TI  - Electronic correlation in the ionization of molecular hydrogen.

PMID- 9911369
TI  - Electromagnetic pair production with capture.

PMID- 9911371
TI  - Atomic charge exchange between fast helium ions and targets from carbon to
      bismuth at beta =0.36.

PMID- 9911372
TI  - Determination of scattering amplitudes from differential cross-section data by
      using unitarity conditions.

PMID- 9911373
TI  - Elastic scattering of electrons by strontium and barium atoms.

PMID- 9911374
TI  - Observation of coherence between the photoionization of different inner-shell
      vacancy states of argon and krypton.

PMID- 9911375
TI  - Inversion of He-Ne elastic-scattering data.

PMID- 9911376
TI  - Coherences in the decay of autoionizing states in photoionization. I. Exchange
      effect between photo- and Auger electrons.

PMID- 9911377
TI  - Coherences in the decay of autoionizing states in photoionization. II. Coherences
      of nondegenerate states.

PMID- 9911380
TI  - Creating and probing subwavelength atomic gratings using spatially separated
      fields.

PMID- 9911378
TI  - Projectile L2,3-shell electron excitation in slow Ne+-Al collisions.

PMID- 9911379
TI  - Charge states of fast ions in glancing collisions with aligned atoms in Si
      crystals.

PMID- 9911382
TI  - Resonant collisions of Na Rydberg atoms in electric and magnetic fields.

PMID- 9911381
TI  - Phonon-induced quantum pair correlation in the diffraction of an ultracold atomic
      beam by a crystalline solid surface.

PMID- 9911383
TI  - Adiabatic stabilization against photoionization: An experimental study.

PMID- 9911384
TI  - Above-threshold multiphoton detachment from the H- ion by 10.6- microm radiation:
      Angular distributions and partial widths.

PMID- 9911385
TI  - Computation of strong-field multiphoton processes in polyelectronic atoms: State
      specific method and applications to H and Li-

PMID- 9911386
TI  - Ion storage in the rf octupole trap.

PMID- 9911388
TI  - Effects of Zeeman degeneracy on the steady-state properties of an atom
      interacting with a near-resonant laser field: Resonance flourescence.

PMID- 9911387
TI  - Ionization suppression of Rydberg atoms by short laser pulses.

PMID- 9911390
TI  - Influence of spontaneous emission on atomic solitons.

PMID- 9911389
TI  - Chaotic transients of two particles in a Paul trap: Interpretation as a boundary
      crisis.

PMID- 9911391
TI  - Laser with injected squeezed vacuum: Phase diffusion and intensity fluctuations.

PMID- 9911392
TI  - Nonlinear theory of a laser with injected atomic coherence.

PMID- 9911393
TI  - Effect of multiphoton ionization on high-order harmonic generation and
      propagation in rare gases with subpicosecond laser pulses.

PMID- 9911395
TI  - Understanding the bifurcation to traveling waves in a class-B laser using a
      degenerate Ginzburg-Landau equation.

PMID- 9911394
TI  - Squeezed Raman micromaser model.

PMID- 9911396
TI  - Phase-coherent states and their squeezing properties.

PMID- 9911397
TI  - Photon noise reduction by reflection from a movable mirror.

PMID- 9911398
TI  - First-order correction to the unified colored-noise approximation and dye-laser
      transients.

PMID- 9911399
TI  - Physical realization of an environment with squeezed quantum fluctuations via
      quantum-nondemolition-mediated feedback.

PMID- 9911400
TI  - Mixed excitation- and deexcitation-operator coherent states for the SU(1,1)
      group.

PMID- 9911402
TI  - Interference in climbing a quantum ladder system with frequency-chirped laser
      pulses.

PMID- 9911401
TI  - Forced light scattering by broad-bandwidth incoherent pump lasers.

PMID- 9911403
TI  - Driven two-level atom.

PMID- 9911404
TI  - One-dimensional coherent-state representation on a circle in phase space.

PMID- 9911405
TI  - Detection of the density matrix through optical homodyne tomography without
      filtered back projection.

PMID- 9911406
TI  - Saturated absorption spectroscopy using diode-laser phase noise.

PMID- 9911407
TI  - Boundary effects in large-aspect-ratio lasers.

PMID- 9911408
TI  - Photon statistics of a cavity-QED laser: A comment on the laser-phase-transition
      analogy.

PMID- 9911409
TI  - Transient macroscopic quantum superposition states in degenerate parametric
      oscillation: Calculations in the large-quantum-noise limit using the positive P
      representation.

PMID- 9911410
TI  - Interference between excitation routes in resonant sum-frequency mixing.

PMID- 9911411
TI  - Quantum radiation of a harmonic oscillator near the planar dielectric-vacuum
      interface.

PMID- 9911412
TI  - Photodetachment of the 2p2(3Pe) state of H-

PMID- 9911413
TI  - Expanding the class of conditionally exactly solvable potentials.

PMID- 9911415
TI  - Spin-orbit pendulum: Oscillations between spin and orbital angular momentum.

PMID- 9911414
TI  - Most general and simplest algebraic relationship between energy eigenstates of a
      hydrogen atom and a harmonic oscillator of arbitrary dimensions.

PMID- 9911416
TI  - Deformational self-consistent approach to high-resolution ir spectra of diatomic
      molecules.

PMID- 9911417
TI  - Different approach to the Zeeman effect: Application to the hydrogen ground
      state.

PMID- 9911418
TI  - Asymmetrical configurations in Coulombic rigid rotators.

PMID- 9911419
TI  - Two-electron systems: Stability analysis of the Wannier ridge.

PMID- 9911420
TI  - Coulomb three-body effects in (e,2e) collisions: The ionization of H in coplanar
      symmetric geometry.

PMID- 9911421
TI  - Optical theorem in N dimensions.

PMID- 9911422
TI  - Calculation of cross sections measured in recoil-type experiments.

PMID- 9911423
TI  - Phase control of scattering resonances in intense bichromatic laser fields.

PMID- 9911425
TI  - Collisional-cross-relaxation effects in amplified-spontaneous-emission lasers.

PMID- 9911424
TI  - Ionization of H Rydberg atoms by microwaves: Pulse-shape influence on the
      algebraic decay.

PMID- 9911426
TI  - Evaluation of GaAs/Al0.3Ga0.7As multiple-quantum-well waveguides for pulsed
      squeezed light generation.

PMID- 9911427
TI  - Completeness relation of the eigenstates of the powers of the radiation-field
      amplitude.

PMID- 9911428
TI  - Comment on "X-ray absorption by atoms under intense laser fields"

PMID- 9911429
TI  - Reply to "Comment on 'X-ray absorption by atoms under intense laser fields' "

PMID- 9911430
TI  - Erratum: Lifetimes and Rydberg-valence state mixing of the c' 1 Sigma g+(v=4) and
      1 Pi u(v=4) states of N2

PMID- 9911431
TI  - Erratum: Quantum theory of continuous feedback

PMID- 9911432
TI  - Erratum: Atomic structure calculations of KLL Auger spectra from highly charged
      ion-solid-surface collisions

PMID- 9911433
TI  - Fractal dimensions in the phase space of two-electron atoms.

PMID- 9911434
TI  - Line shapes for light scattered from Bose-Einstein condensates.

PMID- 9911435
TI  - Angular anisotropy in the resonant Auger decay of 2p-photoexcited Mg.

PMID- 9911437
TI  - Atom-optical gratings induced by multiphoton excitation of electronic Rydberg
      wave packets.

PMID- 9911436
TI  - Double photoionization of helium using R-matrix methods.

PMID- 9911438
TI  - Enhanced loading of a magneto-optic trap from an atomic beam.

PMID- 9911439
TI  - High-harmonic generation and correlated two-electron multiphoton ionization with
      elliptically polarized light.

PMID- 9911440
TI  - Quantum conversion between the cavity fields and the center-of-mass motion of
      ions in a quantized trap.

PMID- 9911442
TI  - Reduction of light-assisted collisional loss rate from a low-pressure vapor-cell
      trap.

PMID- 9911441
TI  - Decay of bichromatically driven atoms in a cavity.

PMID- 9911443
TI  - Transverse patterns in lasers.

PMID- 9911445
TI  - Formulations of certain Gel'fand-Levitan and Marchenko equations.

PMID- 9911444
TI  - Probing the two-photon phase coherence of parametrically down-converted photons
      by a local oscillator.

PMID- 9911446
TI  - Continuum bound states.

PMID- 9911447
TI  - Displaced and squeezed parity operator: Its role in classical mappings of quantum
      theories.

PMID- 9911448
TI  - Quantum nonlocality in a delayed-choice experiment with partial, controllable
      memory erasing.

PMID- 9911449
TI  - Perturbed ladder-operator method: An algebraic recursive solution of the
      perturbed Morse-oscillator eigenequation.

PMID- 9911450
TI  - Quantum electrodynamic theory of recombination of an electron with a highly
      charged ion.

PMID- 9911451
TI  - Bound states of two-dimensional nonuniform waveguides.

PMID- 9911452
TI  - Canonical transformations and path-integral measures.

PMID- 9911454
TI  - Simultaneous sharp measurability of position and momentum in infinite quantum
      systems.

PMID- 9911453
TI  - Size-consistent Brillouin-Wigner perturbation theory with an exponentially
      parametrized wave function: Brillouin-Wigner coupled-cluster theory.

PMID- 9911456
TI  - Dynamical quantum Zeno effect.

PMID- 9911455
TI  - Topological quenching of the tunnel splitting for a particle in a double-well
      potential on a planar loop.

PMID- 9911457
TI  - Taylor-series expansion of density functionals.

PMID- 9911458
TI  - Floquet spectroscopy of hydrogenic states: Classical and quantal descriptions.

PMID- 9911459
TI  - Multichannel quantum-defect theory of n=2 and 3 gerade states in H2: Rovibronic
      energy levels.

PMID- 9911460
TI  - Distortion of atomic states by time-dependent electric fields. II. Coupling to
      the continuum.

PMID- 9911461
TI  - Precision measurement of the hyperfine structure and nuclear moments of 180mTa by
      laser-rf double resonance.

PMID- 9911462
TI  - Test of a bond-pair superposition model describing the interaction between atoms:
      Application to the hydrides of the first-row elements.

PMID- 9911464
TI  - Measurement of the Stark-induced amplitudes of the 6P1/2-->7P1/2 transition in
      atomic thallium.

PMID- 9911463
TI  - Forward scattering magneto-optical spectra of the Cs D2 line.

PMID- 9911466
TI  - Large-field behavior of the LoSurdo-Stark resonances in atomic hydrogen.

PMID- 9911465
TI  - Many-body calculation of the 2p1/2,3/2-2s1/2 transition energies in Li-like 238U.

PMID- 9911467
TI  - Theoretical triple differential cross section of the helium atom ionization with
      excitation to the n=2 ion state.

PMID- 9911468
TI  - Assessment of Kohn-Sham density-functional orbitals as approximate Dyson orbitals
      for the calculation of electron-momentum-spectroscopy scattering cross sections.

PMID- 9911469
TI  - Measurement of a linear Stark interference effect on the rubidium D1 absorption
      line.

PMID- 9911470
TI  - Relativistic many-body perturbation theory based on the no-pair Dirac-Coulomb
      Breit Hamiltonian: Relativistic correlation energies for the noble-gas sequence
      through Rn (Z=86), the group-IIB atoms through Hg, and the ions of Ne
      isoelectronic sequence.

PMID- 9911471
TI  - Theory of muon-spin relaxation of simple gaseous free radicals.

PMID- 9911472
TI  - Maxwell fields and Poynting vector in the proximity of a chiral molecule.

PMID- 9911473
TI  - Retarded dispersion interaction energies between chiral molecules.

PMID- 9911474
TI  - Dependence of electron-impact dissociative excitation cross sections on the
      initial vibrational quantum number in H2 and D2 molecules: X 1 Sigma g+-->B 1
      Sigma u+ and X 1 Sigma g+-->C 1 Pi u transitions.

PMID- 9911475
TI  - Excitation transfer among, and quenching of, the barium 6s5d 3DJ metastable
      levels due to collisions with argon, nitrogen, and barium perturbers.

PMID- 9911476
TI  - Absolute differential cross sections for the excitation of molecular oxygen by
      electron impact: Decomposition of the Schumann-Runge continuum.

PMID- 9911477
TI  - 29-state R-matrix investigation of resonances in e--He scattering at low
      energies: 1 (1)S-3 (3),1S and 1 (1)S-4 (3),1S excitation cross sections.

PMID- 9911478
TI  - Subexcitation electron interactions in rare gases: Production of electronic
      excited states in helium or neon mixtures with argon, krypton, or xenon.

PMID- 9911480
TI  - Elastic scattering of two Na atoms.

PMID- 9911479
TI  - Positron scattering from krypton and xenon.

PMID- 9911481
TI  - Photoionization of palladium including relaxation effects.

PMID- 9911482
TI  - Convergence of bound-electron-positron pair production calculations for
      relativistic heavy-ion collisions.

PMID- 9911483
TI  - Electron capture and excitation in collisions of O+(4S,2D,2P) ions with He atoms
      and He+ ions with O atoms at energies below 10 keV.

PMID- 9911484
TI  - Low-energy differential scattering of electrons and positrons from noble gases.

PMID- 9911486
TI  - Doubly excited shape resonance states in H- above the hydrogen N=5 threshold.

PMID- 9911485
TI  - Direct double photoionization of atomic sodium.

PMID- 9911487
TI  - 3Do shape-resonant state of H- lying above the hydrogen N=3 threshold.

PMID- 9911488
TI  - Vibrational and rotational population distributions of MgH(v"=0 and 1) produced
      in the reaction of Mg(3s3p 1P1) with H2.

PMID- 9911489
TI  - Identification of inelastic processes in 4.0-keV H2+-He collisions using L alpha 
      photon-particle coincidence techniques.

PMID- 9911490
TI  - Backward ejected electrons produced by 1-MeV/u Oq+ (q=3-8) projectile ions
      colliding with argon gas.

PMID- 9911491
TI  - Excitation-autoionization through 3d-4l inner-shell excitations in Cu- to Kr-like
      ions and the effect on fractional-ion-abundance balance in coronal plasmas.

PMID- 9911492
TI  - Generalized Hofstadter picture for lattices with more than one degree of freedom
      per site.

PMID- 9911493
TI  - Electric-field effects on the N=3 (1)Po(1) resonance of H-

PMID- 9911494
TI  - Ionization of excited hydrogen atoms by collisions with bare ions.

PMID- 9911495
TI  - Muon transfer and elastic scattering in t+d micro collisions at low energies.

PMID- 9911496
TI  - Evolution of barium autoionizing Stark spectra with energy and field.

PMID- 9911497
TI  - Interference effects in the recombination process of hydrogenlike lead.

PMID- 9911499
TI  - Target effects in the interaction of highly charged Ne ions with an Al(110)
      surface.

PMID- 9911498
TI  - Impact-parameter dependence of energy loss for 625-keV H+ ions in Si single
      crystals.

PMID- 9911500
TI  - Contrast enhancement by time selection in neutron interferometry.

PMID- 9911502
TI  - Density-matrix description of neutron-interferometry experiments.

PMID- 9911501
TI  - Dispersive and nondispersive phase shifts in atomic Stern-Gerlach interferometry.

PMID- 9911503
TI  - Classical stabilization of periodically kicked hydrogen atoms.

PMID- 9911504
TI  - Photoassociation of atoms in ultracold collisions probed by wave-packet dynamics.

PMID- 9911505
TI  - Laser-induced trapping of chlorine molecules with pico- and femtosecond pulses.

PMID- 9911506
TI  - Multiphoton absorption via chirped-pulse adiabatic passage: Dynamics within the
      excited-state manifolds.

PMID- 9911507
TI  - Mechanical Faraday effect induced by binary collisions.

PMID- 9911509
TI  - Resonant two-photon transition to the continuum from an initial J=0 state using
      elliptically polarized light.

PMID- 9911508
TI  - Mg 3pnk autoionizing states in electric fields.

PMID- 9911510
TI  - Approximate dynamical symmetry of hydrogen atoms in circularly polarized
      microwave fields.

PMID- 9911511
TI  - Theory of strong-field light-induced collisional energy transfer in Eu and Sr.

PMID- 9911512
TI  - Two-dimensional Sisyphus cooling.

PMID- 9911513
TI  - Cavity field spectra of the nondegenerate two-photon Jaynes-Cummings model.

PMID- 9911514
TI  - Theory of two-photon entanglement in type-II optical parametric down-conversion.

PMID- 9911515
TI  - Theoretical description of steady-state sum-frequency generation in molecular
      adsorbates.

PMID- 9911516
TI  - Soliton states in wave mixing and third-harmonic generation.

PMID- 9911517
TI  - Bistability and symmetry breaking in distributed coupling of counterpropagating
      beams into nonlinear waveguides.

PMID- 9911518
TI  - Wave-field phase singularities: The sign principle.

PMID- 9911519
TI  - Crystallography of optical lattices.

PMID- 9911521
TI  - Dynamics of light transmission in two-dimensional nonlinear optical
      superlattices.

PMID- 9911520
TI  - Effects of pulses with simple phase and frequency modulations.

PMID- 9911522
TI  - Stability of vector solitary waves.

PMID- 9911523
TI  - Photon generation and squeezing in a generalized two-dimensional oscillator.

PMID- 9911524
TI  - Nonlinear optical transmission in multiple quantum wells with ridged waveguides:
      Experiment and theory.

PMID- 9911525
TI  - Statistical and phase properties of the binomial states of the electromagnetic
      field.

PMID- 9911526
TI  - Linear stochastic wave equations for continuously measured quantum systems.

PMID- 9911527
TI  - Quantum-limited measurements with the atomic force microscope.

PMID- 9911528
TI  - Quantum-classical correspondences for atomic operators: A doubled atomic-space
      approach.

PMID- 9911529
TI  - Infinite set of relevant operators for an exact solution of the time-dependent
      Jaynes-Cummings Hamiltonian.

PMID- 9911530
TI  - Bright squeezing from self-induced transparencies in dressed three-level atoms.

PMID- 9911531
TI  - Enhanced squeezing by periodic frequency modulation under parametric instability
      conditions.

PMID- 9911532
TI  - SU(m,n) coherent states in the bosonic representation and their generation in
      optical parametric processes.

PMID- 9911534
TI  - Equivalence between Aharonov-Bohm and Aharonov-Casher effects, and motive forces.

PMID- 9911533
TI  - Structure of the solution of the time-dependent Schrodinger equation, universal
      existence of the cyclic quantum evolution, and geometric phases.

PMID- 9911535
TI  - Continuum limit of the fluctuation factor in coherent-state functional integrals
      for transition amplitudes.

PMID- 9911536
TI  - Obtaining a gradient-corrected kinetic-energy functional from the Perdew-Wang
      exchange functional.

PMID- 9911538
TI  - Two electrons in an external oscillator potential: The hidden algebraic
      structure.

PMID- 9911537
TI  - Reinterpretation of pion-transfer probabilities in mixtures of H2O and D2O.

PMID- 9911540
TI  - Squeezing in Zak's kq representation.

PMID- 9911539
TI  - Low-energy electron emission in proton-helium collisions.

PMID- 9911541
TI  - Analysis of the lifetimes and fractions of antiprotons trapped in metastable
      states of antiprotonic helium.

PMID- 9911543
TI  - Erratum: Dynamical ordering: Applications to Fokker-Planck equations

PMID- 9911542
TI  - Reply to "Analysis of the lifetimes and fractions of antiprotons trapped in
      metastable states of antiprotonic helium"

PMID- 9911544
TI  - Erratum: Quantum dynamics of a laser-cooled ideal gas

PMID- 9911545
TI  - Schemes for atomic-state teleportation.

PMID- 9911546
TI  - Quantum defects and the long-term behavior of radial Rydberg wave packets.

PMID- 9911547
TI  - Comparison of the cold-collision losses for laser-trapped sodium in different
      ground-state hyperfine sublevels.

PMID- 9911548
TI  - Prediction of an alignment transition region of two-ion crystals in a Paul trap.

PMID- 9911550
TI  - Optimal quasi-phase-matching for high-order harmonic generation in gases and
      plasma.

PMID- 9911549
TI  - Dark and bright photovoltaic spatial solitons.

PMID- 9911551
TI  - Realization of trapping in a two-level system with frequency-modulated fields.

PMID- 9911552
TI  - Non- and nearly hexagonal patterns in sodium vapor generated by single-mirror
      feedback.

PMID- 9911553
TI  - "Weak measurements" and the "quantum time-translation machine" in a classical
      system.

PMID- 9911555
TI  - Two interferometric complementarities.

PMID- 9911554
TI  - Nature of geometric (Berry) potentials.

PMID- 9911557
TI  - Solutions of the Schrodinger equations for lithium and excited helium (2 (1)S)
      atoms with a correlation-function hyperspherical harmonic and generalized
      Laguerre-function expansion method.

PMID- 9911556
TI  - Singular Lagrangians as field systems.

PMID- 9911558
TI  - Changing the relative amplitudes of wave packets to induce nonlocal effects.

PMID- 9911559
TI  - Canonical and measured phase distributions.

PMID- 9911560
TI  - Proper time derivatives in quantum mechanics.

PMID- 9911561
TI  - Collapse and revival in the dynamics of a spin with the spin-orbit potential.

PMID- 9911562
TI  - Phase of neutrons propagating through an accelerating interferometer: A test of
      the equivalence principle.

PMID- 9911563
TI  - Non-numerical determination of the number of bound states in some screened
      Coulomb potentials.

PMID- 9911564
TI  - Schrodinger cat states and single runs for the damped harmonic oscillator.

PMID- 9911565
TI  - Experimental lifetimes for the 3p 2P levels in Na-like Nb (Nb30+).

PMID- 9911566
TI  - Multielectron excitations in the L-subshell photoabsorption of xenon.

PMID- 9911567
TI  - Hyperspherical-coordinate approach to one-dimensional models of two-electron
      quantum systems.

PMID- 9911568
TI  - N-electron wave functions described with hyperspherical coordinates.

PMID- 9911569
TI  - Energy expressions in density-functional theory using line integrals.

PMID- 9911570
TI  - Experimental lifetimes for Mg-like chlorine.

PMID- 9911571
TI  - Relativistic Thomas-Fermi formulations with thermal effects for an atom within
      and without a very strong magnetic field.

PMID- 9911573
TI  - 6s and 4f ionized states of the lanthanides calculated by numerical and
      analytical Hartree-Fock methods.

PMID- 9911572
TI  - Barium spectrum in high magnetic fields.

PMID- 9911574
TI  - Energies and widths of triply excited n=2 intrashell autoionizing states of He-

PMID- 9911576
TI  - Line-shape analysis of speed-dependent collisional width inhomogeneities in CO
      broadened by Xe, N2, and He.

PMID- 9911575
TI  - Xenon 147-nm resonance f value and trapped decay rates.

PMID- 9911577
TI  - Relativistic coupled-cluster method: Intrashell excitations in the f2 shells of
      Pr+3 and U+4.

PMID- 9911579
TI  - Nonadditive intermolecular forces from the spectroscopy of van der Waals trimers:
      A theoretical study of Ar2-HF.

PMID- 9911578
TI  - Isotope shift in the electron affinity of chlorine.

PMID- 9911580
TI  - Data-based predictions of line strengths in alkali-metal-like isoelectronic
      sequences.

PMID- 9911581
TI  - Decomposition of the two-electron-atom eigenvalue problem.

PMID- 9911583
TI  - Relativistic and correlation effects in the ground state of atomic lawrencium.

PMID- 9911582
TI  - Quasiclassical effective Hamiltonian structure of atoms with Z=1 to 38.

PMID- 9911584
TI  - K alpha and K beta x-ray emission spectra of copper.

PMID- 9911585
TI  - Theory of 2s1/2-2p3/2 transitions in highly ionized uranium.

PMID- 9911586
TI  - X-ray absorption structures of multielectron excitation in Br.

PMID- 9911587
TI  - Elastic scattering of positrons off rare-gas atoms.

PMID- 9911588
TI  - Measurement of the K-shell photoionization cross section of C IV through the L
      shell photoabsorption spectra.

PMID- 9911589
TI  - Projectile energy loss in multiply ionizing ion-atom collisions.

PMID- 9911590
TI  - Kinetic-energy distributions of O- produced by dissociative electron attachment
      to physisorbed O2.

PMID- 9911591
TI  - Time-ordering effects in K-shell excitation of 170-MeV Ne7+ colliding with gas
      atoms: Double excitation.

PMID- 9911593
TI  - Spectra of L x rays from fast highly charged Xe ions traveling in solids.

PMID- 9911592
TI  - Coulomb and screening corrections to Delbruck forward scattering.

PMID- 9911594
TI  - Photoionization of the Be isoelectronic sequence from the ground and the 1S bound
      excited states.

PMID- 9911595
TI  - Theoretical charge-exchange Galilean invariant cross sections for the B3++He
      collision.

PMID- 9911596
TI  - Kinetic-energy release in CO dissociation caused by fast F4+ impact.

PMID- 9911597
TI  - Ratio of double to single ionization of helium: The relationship between
      ionization by photons and by bare charged particles.

PMID- 9911598
TI  - Temporary negative-ion states of Na, K, Rb, and Cs.

PMID- 9911599
TI  - Absolute total-cross-section measurements for intermediate-energy electron
      scattering on C2H2 and CO.

PMID- 9911601
TI  - Photon-electron polarization correlations in highnpJ-subshell photoionizat.

PMID- 9911600
TI  - (e,3e) observation of the angular correlation between ejected and Auger electrons
      in the double ionization of magnesium.

PMID- 9911602
TI  - Multiconfiguration self-consistent-field ab initio and local-density-functional
      studies on the vibrational structure of core-level photoelectron spectra of SiH4
      and GeH4.

PMID- 9911604
TI  - Many-body theory of electron scattering by excited atomic targets: Electron
      impact-induced transitions 2 (1),3S-->n 1,3L (L=0,1,2; n=2,3,4) in helium.

PMID- 9911603
TI  - Attenuation of photons at 3-14-keV energies in helium.

PMID- 9911605
TI  - Measurements of positron-annihilation rates on molecules.

PMID- 9911607
TI  - Theory of double photoionization of a two-electron atom: Circumventing the
      boundary conditions.

PMID- 9911606
TI  - Resonance structure in the 4s2(1S0)-->4s4p(3P0,1,2) electron-impact excitation of
      Kr6+

PMID- 9911608
TI  - Calculation of electron-helium scattering at 40 eV.

PMID- 9911609
TI  - Impact-parameter dependence for collisions of atoms with projectiles carrying
      electrons.

PMID- 9911610
TI  - Spin-orbit effects in aluminum photoionization.

PMID- 9911612
TI  - Inelastic energy loss of H2+ and H3+ ions correlated with molecular orientation.

PMID- 9911611
TI  - Dissociative scattering of fast HeH+ ions at glancing-angle incidence on a
      crystal surface.

PMID- 9911613
TI  - Statistical theory of energy loss and charge exchange of penetrating particles:
      Energy-loss spectra and applications.

PMID- 9911614
TI  - Multiple-charged secondary-ion emission from silicon and silicon oxide bombarded
      by heavy ions at energies of 0.4-10 MeV.

PMID- 9911615
TI  - Laser-assisted inelastic rescattering during above-threshold ionization.

PMID- 9911616
TI  - Excited-state nonlinear absorption in multi-energy-level molecular systems.

PMID- 9911617
TI  - Electromagnetically induced transparency in ladder-type inhomogeneously broadened
      media: Theory and experiment.

PMID- 9911618
TI  - High-order harmonic generation in laser-produced ions using a near-infrared
      laser.

PMID- 9911620
TI  - Photodetachment of an electron bound by a zero-range potential in magnetic fields
      of arbitrary strength.

PMID- 9911619
TI  - Collisional transfer of electronic state coherence.

PMID- 9911622
TI  - Cooling-induced melting of ion crystals in a Paul trap.

PMID- 9911621
TI  - Rydberg-electron wave-packet dynamics in parallel electric and magnetic fields
      and evidence for stabilization.

PMID- 9911624
TI  - Photoionization by a bichromatic field: Adiabatic theory.

PMID- 9911623
TI  - Dipole coupling of atoms and light in gravitational fields.

PMID- 9911625
TI  - Mode dynamics in optical cavities.

PMID- 9911626
TI  - Observation of Landau-Zener dynamics in classical optical systems.

PMID- 9911627
TI  - Electrostrictive generation of nonresonant gratings in the gas phase by multimode
      lasers.

PMID- 9911628
TI  - Investigation of a CO2 laser response to loss perturbation near period doubling.

PMID- 9911630
TI  - Photonic superguiding state in nonlinear polar crystals.

PMID- 9911629
TI  - Physical origin of dynamical stimulated Brillouin scattering in optical fibers
      with feedback.

PMID- 9911631
TI  - Polarization interaction of spatial solitons in optical planar waveguides.

PMID- 9911632
TI  - Second-harmonic generation of nonlinear optical crystals in vacuum-ultraviolet
      and x-ray regions.

PMID- 9911633
TI  - Nonlinear optical properties of dimers of polar molecules in the intermediate
      stochastic regime.

PMID- 9911634
TI  - Cavity-induced decay of Floquet states in a bichromatic driving field.

PMID- 9911635
TI  - Creating number states in the micromaser using feedback.

PMID- 9911636
TI  - Spontaneous emission in a standing-wave cavity: Quantum-mechanical center-of-mass
      motion.

PMID- 9911637
TI  - Four-photon homoclinic instabilities in nonlinear highly birefringent media.

PMID- 9911638
TI  - Quantum trajectories and classical attractors in second-harmonic generation.

PMID- 9911639
TI  - Photon-assisted transmission through an oscillating quantum well: A transfer
      matrix approach to coherent destruction of tunneling.

PMID- 9911640
TI  - Theory for the linewidth of a bad-cavity laser.

PMID- 9911641
TI  - General quantum theory of nonlinear optical-pulse propagation.

PMID- 9911642
TI  - Lasers without inversion in a Doppler-broadened medium.

PMID- 9911643
TI  - Electric-quadrupole lines of Mo XVI.

PMID- 9911644
TI  - Vacuum polarization as a test of C and CPT invariance.

PMID- 9911646
TI  - 2s2p2p 4P state of He-

PMID- 9911645
TI  - Quantum defects and atomic core radii.

PMID- 9911647
TI  - Ionization of the excited states of hydrogen by proton impact.

PMID- 9911649
TI  - Calculation of the electron-scattering lengths for the rare-gas atoms.

PMID- 9911648
TI  - Convoy electrons for collisions between projectile He+ and C foils from 17.5 to
      25 keV/amu.

PMID- 9911650
TI  - High-resolution study of the Xe 4d5/2:4d3/2 branching ratio.

PMID- 9911651
TI  - Comment on "Phase-difference operator"

PMID- 9911652
TI  - Reply to "Comment on 'Phase-difference operator' "

PMID- 9911653
TI  - Quadrature squeezing in the nondegenerate parametric amplifier.

PMID- 9911654
TI  - Erratum: Relativistic corrections to the Zeeman effect in heliumlike atoms

PMID- 9911655
TI  - Zero-kinetic-energy electron spectroscopy of the predissociating A2 Sigma + state
      of HBr+

PMID- 9911656
TI  - Dimensional perturbation theory for weakly bound systems.

PMID- 9911657
TI  - Effect of the Mo-slashller interaction on electron-impact ionization of high-Z
      hydrogenlike ions.

PMID- 9911658
TI  - Relativistic calculations of cross sections for ionization of U90+ and U91+ ions
      by electron impact.

PMID- 9911659
TI  - Near-field imaging of atom diffraction gratings: The atomic Talbot effect.

PMID- 9911660
TI  - Ultracold photoassociative ionization collisions in an atomic beam: Optical field
      intensity and polarization dependence of the rate constant.

PMID- 9911662
TI  - Superdressed H2+ and H32+ molecular ions in intense, high-frequency laser fields.

PMID- 9911661
TI  - Permanent magnet trap for cold atoms.

PMID- 9911663
TI  - Dynamic Kingdon trap.

PMID- 9911664
TI  - Field-induced dipole effects in laser-assisted elastic electron-atom scattering.

PMID- 9911665
TI  - Bright spatiotemporal optical solitons in a planar optical waveguide.

PMID- 9911667
TI  - Closed orbits and shell effects in semiclassical response functions.

PMID- 9911666
TI  - Twin-hole dark solitons.

PMID- 9911668
TI  - Optimal control of chaotic Hamiltonian dynamics.

PMID- 9911669
TI  - Completely transparent potentials for the Schrodinger equation.

PMID- 9911670
TI  - Geometric spin and charge.

PMID- 9911671
TI  - Unitary transformations for the time-dependent quantum oscillator.

PMID- 9911672
TI  - Controllability of molecular systems.

PMID- 9911673
TI  - Dynamics of quantum collapse in energy measurements.

PMID- 9911674
TI  - Multiparticle correlations in quaternionic quantum systems.

PMID- 9911675
TI  - Non-Hermitian techniques of canonical transformations in quantum mechanics.

PMID- 9911676
TI  - Bell's inequality for an entanglement of nonorthogonal states.

PMID- 9911677
TI  - Maintaining coherence in quantum computers.

PMID- 9911678
TI  - Higher-order processes in the electromagnetic production of electron-positron
      pairs in relativistic heavy-ion collisions.

PMID- 9911679
TI  - Two-bit gates are universal for quantum computation.

PMID- 9911681
TI  - Half-cycle pulse acting on a one-dimensional Rydberg atom: Semiclassical
      transition amplitudes in action and angle variables.

PMID- 9911680
TI  - Semiclassical treatment of a half-cycle pulse acting on a one-dimensional Rydberg
      atom.

PMID- 9911682
TI  - Decay of the resonantly excited states of atomic Kr.

PMID- 9911683
TI  - 3 (1) Pi u and 3 (1) Sigma u+ states of K2 studied by a polarization-labeling
      spectroscopy technique.

PMID- 9911685
TI  - Electric quadrupole transitions in x-ray spectra: 3d transition-metal oxides.

PMID- 9911684
TI  - Green's-function calculations of valence photoemission spectra of titanium
      halides.

PMID- 9911686
TI  - Evaluation of high-level bound-bound and bound-continuum hydrogenic oscillator
      strengths by asymptotic expansion.

PMID- 9911687
TI  - Multireferent superposition-of-configurations calculations of core-correlation
      effects on energy levels and oscillator strengths: Be and B+

PMID- 9911688
TI  - Radius of convergence of the 1/Z expansion for the ground state of a two-electron
      atom.

PMID- 9911689
TI  - Onset of a collisional modification of the Faraday effect in a high-density
      atomic gas.

PMID- 9911690
TI  - Four-photon excitation of autoionizing states of Ar, Kr, and Xe between the 2P3/2
      and 2P1/2 ionic limits.

PMID- 9911692
TI  - Nuclear-polarization contribution to the Lamb shift in actinide nuclei.

PMID- 9911691
TI  - Total eigenphase description of multiparticle quantum systems.

PMID- 9911693
TI  - Projection operators in multiconfiguration Dirac-Fock calculations: Application
      to the ground state of heliumlike ions.

PMID- 9911694
TI  - Tiling rules for toroidal molecules.

PMID- 9911695
TI  - Atomic energy-level shifts near a dielectric microsphere.

PMID- 9911696
TI  - Autocorrelation functions in the photoionization of hydrogen in electric and
      magnetic fields.

PMID- 9911697
TI  - Alternative form of the linear-response contribution to the exchange-correlation
      energy functional.

PMID- 9911698
TI  - Full QED calculations of two-photon exchange for heliumlike systems: Analysis in
      the Coulomb and Feynman gauges.

PMID- 9911699
TI  - Relativistic many-body calculations of

PMID- 9911700
TI  - Collison-induced absorption by H2-He pairs in the H2 fundamental band at 78 and
      298 K.

PMID- 9911702
TI  - Free-free transitions in collisions between slow electrons and neutral oxygen
      atoms.

PMID- 9911701
TI  - Electron-impact excitation cross-section measurements of highly charged
      heliumlike and lithiumlike ions.

PMID- 9911703
TI  - Time-dependent quantum-mechanical treatment for molecular collisions.

PMID- 9911704
TI  - Rotational-angular-momentum relaxation mechanisms in the energy-corrected-sudden
      scaling theory.

PMID- 9911705
TI  - Incident-photon energy-distribution effects on radiationless resonant Raman
      scattering.

PMID- 9911706
TI  - Semiclassical theory of elastic electron-atom scattering.

PMID- 9911708
TI  - Coherent control of H- photodetachment in parallel static electric and magnetic
      fields.

PMID- 9911707
TI  - Direct production of electron-positron pairs by 200-GeV/nucleon oxygen and sulfur
      ions in nuclear emulsion.

PMID- 9911709
TI  - Efficient direct calculation of complex resonance (Siegert) energies.

PMID- 9911710
TI  - Photoionization of the beryllium atom.

PMID- 9911711
TI  - Correlation effects in the resonant Auger decay of the Xe 4d3/2,5/2-1 6p states
      studied by high-resolution experiment and multiconfiguration Dirac-Fock theory.

PMID- 9911712
TI  - Energy-transfer processes during Xe30+-Ar collisions for projectile velocities
      between 0.3 and 1.0 a.u.

PMID- 9911713
TI  - Radiative electron capture by bare and H-like Si and Cl ions using the channeling
      technique and the associated solid-state effect.

PMID- 9911715
TI  - Comparative study of exchange-correlation effects on the electronic and optical
      properties of alkali-metal clusters.

PMID- 9911714
TI  - Charge transfer between the 2p2 3P ground-state O2+ ion and He, H2, N2, and CO at
      electron-volt energies.

PMID- 9911716
TI  - Recombination of D+ and He+ ions with low-energy free electrons.

PMID- 9911718
TI  - Single-electron detachment cross sections for 5-50-keV H- ions incident on
      helium, neon, and argon atoms.

PMID- 9911717
TI  - Electron capture from circular Rydberg atoms.

PMID- 9911720
TI  - Quantum-mechanical treatment of high-energy channeling radiation.

PMID- 9911719
TI  - Curvature in the scattered-beam growth curves in H-+(He,Ne,Ar) collisions.

PMID- 9911721
TI  - Z1 oscillations in yields of multicharged ions emitted from a germanium surface
      when bombarded by light ions.

PMID- 9911722
TI  - Numerical solution of the nonlinear Schrodinger equation for small samples of
      trapped neutral atoms.

PMID- 9911723
TI  - Time-resolved dynamics of two-channel molecular systems in cw laser fields: Wave
      packet construction in the Floquet formalism.

PMID- 9911725
TI  - Effective stimulated laser cooling of atoms with a three-level Lambda
      configuration by two negatively detuned standing light waves.

PMID- 9911724
TI  - Creating long-lived neutral-atom traps in a cryogenic environment.

PMID- 9911727
TI  - Monte Carlo classical simulations of ionization and harmonic generation in the
      relativistic domain.

PMID- 9911726
TI  - Production of an extremely cold plasma by optical-field-induced ionization.

PMID- 9911728
TI  - Laser-induced nuclear motions in the Coulomb explosion of C2H2+ ions.

PMID- 9911729
TI  - Experimental investigations of absorption and dispersion profiles of a strongly
      driven transition: ssV-shaped three-level system with a strong probe.

PMID- 9911730
TI  - Optical shielding of cold collisions.

PMID- 9911731
TI  - Pulse-shape effects and blueshifting in the single-atom harmonic generation from
      neutral species and ions.

PMID- 9911733
TI  - Light-induced states of H and H-, shadow states, and the dressed potential.

PMID- 9911732
TI  - Formation of hot electrons in noble gases by intense-field ionization: A
      quasistatic tunneling, independent-electron model.

PMID- 9911735
TI  - Ionization of Rydberg hydrogen by a half-cycle pulse.

PMID- 9911734
TI  - Interaction of a strong laser pulse with the S1/2-P1/2,3/2 system.

PMID- 9911736
TI  - Rings in above-threshold ionization: A quasiclassical analysis.

PMID- 9911737
TI  - Ionization of hydrogen atoms by circularly polarized microwaves.

PMID- 9911738
TI  - Propagation of an optical beam in a photorefractive medium in the presence of a
      photogalvanic nonlinearity or an externally applied electric field.

PMID- 9911739
TI  - Concentrational effects in anisotropic artificial Kerr media.

PMID- 9911740
TI  - Spatiotemporal dynamics of coupled-transverse-mode oscillations in unidirectional
      photorefractive ring resonators.

PMID- 9911741
TI  - Dynamic stabilization of self-trapped solitary waves in cubic nonlinear media: A
      route to multidimensional solitons.

PMID- 9911743
TI  - Self-phase-modulation and high-power steady-state pulses in a weakly ionized
      coherent amplifier.

PMID- 9911742
TI  - van der Waals interactions between excited-state atoms and dispersive dielectric
      surfaces.

PMID- 9911744
TI  - Nonlinear surface optical waves in photorefractive crystals with a diffusion
      mechanism of nonlinearity.

PMID- 9911745
TI  - Quantum-state mapping between multilevel atoms and cavity light fields.

PMID- 9911746
TI  - Uncertainties of Schwinger angular-momentum operators for squeezed radiation in
      interferometers.

PMID- 9911748
TI  - Classical equations for quantum squeezing and coherent pumping by the time
      dependent quadratic Hamiltonian.

PMID- 9911747
TI  - Continuous measurement of photon number for superpositions of coherent states.

PMID- 9911749
TI  - Interband quantum coherence in intersubband coupled quantum wells.

PMID- 9911750
TI  - Distance between density operators: Applications to the Jaynes-Cummings model.

PMID- 9911751
TI  - Control of Young's fringes visibility by stimulated down-conversion.

PMID- 9911752
TI  - Phase properties of light propagating in a Kerr medium: Stokes parameters versus
      Pegg-Barnett predictions.

PMID- 9911753
TI  - Quantum theory of the one-mode Lambda -type micromaser and laser.

PMID- 9911755
TI  - Quantum noise reduction in optical imaging: Role of the spatial coherence of the
      source.

PMID- 9911754
TI  - Laser cooling a trapped atom in a cavity: Bad-cavity limit.

PMID- 9911756
TI  - Photoelectron statistics of solitons corrupted by amplified spontaneous emission.

PMID- 9911757
TI  - Quantum scars and classical ghosts.

PMID- 9911758
TI  - Dirac's equation in semiclassical physics.

PMID- 9911759
TI  - Electron field-emission data, quantum mechanics, and the classical stochastic
      theories.

PMID- 9911760
TI  - Electron affinities of 6p electrons in Pr-

PMID- 9911762
TI  - Angular distributions of N+ from N22+ produced by electron impact on N2.

PMID- 9911761
TI  - Measurement of the 3d-4f transition in Ni-like Er for use in a photopumped x-ray
      laser scheme.

PMID- 9911763
TI  - D-D fusion induced by oxygen clusters impacting deuterated ice targets.

PMID- 9911764
TI  - Short-pulse population inversion and transmittance.

PMID- 9911765
TI  - Nonclassical properties of correlated two-mode Schrodinger cat states.

PMID- 9911766
TI  - Physical aspect of the improvement of quantum-noise characteristics caused by
      unitary transformation with a nonlinear optical medium.

PMID- 9911767
TI  - Normal ordering of the SU(1,1) and SU(2) squeeze operators.

PMID- 9911768
TI  - Comment on "Saddle-point shifts in ionizing collisions"

PMID- 9911769
TI  - Reply to "Comment on 'Saddle-point shifts in ionizing collisions' "

PMID- 9911770
TI  - Erratum: Direct numerical approach to electron-hydrogen scattering. II. L>0

PMID- 9911771
TI  - Precise atomic radiative lifetime via photoassociative spectroscopy of ultracold
      lithium.

PMID- 9911772
TI  - Light-by-light scattering contribution to the decay rate of orthopositronium at
      order alpha 2 Gamma LO.

PMID- 9911773
TI  - Internal conversion in highly stripped 83Kr ions.

PMID- 9911774
TI  - Observation of parity-unfavored transitions in the nonresonant photoionization of
      argon.

PMID- 9911775
TI  - Fragment spin multiplicities in the fission Ag232+-->Ag12++Ag11+

PMID- 9911776
TI  - Trap-loss collisions of ultracold lithium atoms.

PMID- 9911777
TI  - Enhancements in the lifetimes of NO Rydberg states in dc electric fields:
      Implications for zero-electron-kinetic-energy photoelectron spectroscopy
      experiments.

PMID- 9911778
TI  - Above-threshold ionization of cesium by 1.9- microm light.

PMID- 9911779
TI  - Energy-yield and conversion-efficiency measurements of high-order harmonic
      radiation.

PMID- 9911780
TI  - Angular distribution of high-order harmonics emitted from rare gases at low
      density.

PMID- 9911781
TI  - Population transfer in cw-excited Rb resulting from mirrorless maser oscillation.

PMID- 9911782
TI  - Microphysical irreversibility and the time-reversal operation.

PMID- 9911783
TI  - Variational principles for ensembles of quantum states.

PMID- 9911785
TI  - Geometric spectral inversion by the WKB approximation.

PMID- 9911784
TI  - Aharonov-Casher phase in an atomic system.

PMID- 9911786
TI  - Phase distributions and large-amplitude states.

PMID- 9911787
TI  - Analysis of the Klein-Gordon Coulomb problem in the Feshbach-Villars
      representation.

PMID- 9911789
TI  - Quantum-mechanical results for a free particle inside a box with general boundary
      conditions.

PMID- 9911788
TI  - Removal of the singularity in the moment-expansion formalism.

PMID- 9911790
TI  - Dynamics of statistical distance: Quantum limits for two-level clocks.

PMID- 9911791
TI  - Semiclassical theory of Rydberg-wave-packet interferometry.

PMID- 9911792
TI  - Impact-parameter dependence of multiple lepton-pair production from
      electromagnetic fields.

PMID- 9911794
TI  - Pure recoil corrections to hydrogen energy levels.

PMID- 9911793
TI  - Exact dynamics of a quantum dissipative system in a constant external field.

PMID- 9911796
TI  - Estimation of counted quantum phase.

PMID- 9911795
TI  - Quantum cryptography with coherent states.

PMID- 9911797
TI  - Impact-parameter dependence of the total probability for electromagnetic electron
      positron pair production in relativistic heavy-ion collisions.

PMID- 9911798
TI  - Nonequilibrium time-dependent functional theory for coupled interacting fields.

PMID- 9911799
TI  - Relativistic corrections to atomic energies from quantum Monte Carlo
      calculations.

PMID- 9911800
TI  - Fine-structure energies for the 1s2s 3S-1s2p 3P transition in heliumlike Ar16+

PMID- 9911801
TI  - Frequency-fluctuation model for line-shape calculations in plasma spectroscopy.

PMID- 9911802
TI  - Calculation of the weakly coupled 1 and 2 (1) Pi twin states of KRb.

PMID- 9911803
TI  - Adiabatic theory for the doubly excited asymmetric states of the helium atom.

PMID- 9911804
TI  - Self-consistent approximation to the Kohn-Sham exchange potential.

PMID- 9911805
TI  - Autocorrelation function and its application to H- in a static electric field.

PMID- 9911806
TI  - Enhanced selective reflection from a thin layer of a dilute gaseous medium.

PMID- 9911808
TI  - Solution to the Kohn-Sham equations using reference densities from accurate,
      correlated wave functions for the neutral atoms helium through argon.

PMID- 9911807
TI  - Cascade processes and the kinetic-energy distribution of pionic hydrogen atoms.

PMID- 9911809
TI  - Effective core polarizabilities in Ba high-l Nsnl double Rydberg atoms.

PMID- 9911810
TI  - Inverted fine structure in highly excited 2F Rydberg states of indium.

PMID- 9911811
TI  - Ab initio studies of the 4s4p2 4P state in Ca-

PMID- 9911812
TI  - Generalization of the optimized-effective-potential model to include electron
      correlation: A variational derivation of the Sham-Schluter equation for the exact
      exchange-correlation potential.

PMID- 9911813
TI  - Beam-laser measurements of lifetimes in SiO+ and N2+

PMID- 9911814
TI  - Multiconfigurational-Dirac-Fock calculation of the 2s2 1S0-2s2p 3P1 spin
      forbidden transition for the Be-like isoelectronic sequence.

PMID- 9911815
TI  - Multiconfigurational Hartree-Fock calculations of hyperfine-induced transitions
      in heliumlike ions.

PMID- 9911816
TI  - Exact exchange-correlation potential and approximate exchange potential in terms
      of density matrices.

PMID- 9911818
TI  - 3d absorption spectra of Sr I through Sr IV.

PMID- 9911817
TI  - Quantum Monte Carlo determination of the lithium 2 (2)S-->2 (2)P oscillator
      strength: Higher precision.

PMID- 9911819
TI  - Electron capture in collisions of N+(5S,3P) with He: The effect of metastable
      ions.

PMID- 9911820
TI  - Medium-resolution studies of extreme-ultraviolet emission from CO by electron
      impact.

PMID- 9911821
TI  - Classical charge-transfer and ionization channels for ion collisions with
      circular Rydberg atoms.

PMID- 9911822
TI  - Correlation effects in the photoionization of Ba(6s6p 1P1): Determination of
      cross sections for production of specific final J states.

PMID- 9911823
TI  - Observation of CH A 2 Delta -->X 2 Pi r and 2 Sigma --->X 2 Pi r emissions in gas
      phase collisions of fast O(3P) atoms with acetylene.

PMID- 9911824
TI  - Radiative electron capture studied in relativistic heavy-ion-atom collisions.

PMID- 9911825
TI  - Double photoionization of excited 1S and 3S states of the helium isoelectronic
      sequence.

PMID- 9911826
TI  - Angular distributions of total LMM Auger electron yields produced by energetic
      He+ ions in Ar, Cl, and S.

PMID- 9911828
TI  - State-selective scaling in electron capture by multicharged ions on light atoms.

PMID- 9911827
TI  - Nuclear-charge and positron-energy dependence of the single-quantum annihilation
      of positrons.

PMID- 9911829
TI  - Differential double-excitation cross sections in 50-150-keV proton-helium
      collisions.

PMID- 9911830
TI  - Single-differential and total ionization cross sections of a hydrogen atom by
      electron impact.

PMID- 9911831
TI  - Electric-field enhancement of dielectronic recombination from a continuum of
      finite bandwidth.

PMID- 9911832
TI  - Absolute-rate coefficient for C3+(2s-->2p) electron-impact excitation.

PMID- 9911834
TI  - Muon transfer from hydrogen and deuterium atoms to neon.

PMID- 9911833
TI  - Measurements of translational energy gain for one- and two-electron transfer in
      slow Arq+-He (q=15-18) collisions.

PMID- 9911835
TI  - Electron-impact ionization of the Fe atom.

PMID- 9911836
TI  - Oscillations in mean capture Q values as functions of the projectile charge in
      slow Xeq+-He (25 <= q <= 44) collisions.

PMID- 9911837
TI  - Semiclassical multichannel perturbed-stationary-state model for rearrangement
      atomic collisions.

PMID- 9911838
TI  - Charge exchange and excitation in H+He2+ and He++H+ collisions using single- and
      multichannel perturbed-stationary-state propagators.

PMID- 9911839
TI  - Energy and angular distributions of electrons from ion impact on atomic and
      molecular hydrogen. I. 20-114-keV H++H2.

PMID- 9911840
TI  - Energy and angular distributions of electrons from ion impact on atomic and
      molecular hydrogen. II. 20-114-keV H++H.

PMID- 9911842
TI  - Wake forces and the transmission yield of H2+ through thin carbon foils.

PMID- 9911841
TI  - Elastic and inelastic scattering of electrons from Ar and Cl.

PMID- 9911843
TI  - Distribution of the number of emitted electrons for MeV H+- and He2+-ion impact
      on metals.

PMID- 9911844
TI  - Energy loss of protons in Zn: Measurements between 2 and 200 keV.

PMID- 9911845
TI  - Semiclassical calculation of the diffusion constant for the Lambda system
      momentum.

PMID- 9911847
TI  - Proton angular distribution following multiphoton dissociative ionization of H2.

PMID- 9911846
TI  - Determination of trapped-ion kinetic energy by the time-of-flight method for free
      ejected ions.

PMID- 9911848
TI  - Cross sections for the multiphoton ionization of sodium in a linearly polarized
      radiation field.

PMID- 9911850
TI  - Fractional quantum revivals in the atomic gravitational cavity.

PMID- 9911849
TI  - Demonstration of amplification of a polarized soft-x-ray laser beam in a neonlike
      germanium plasma.

PMID- 9911851
TI  - Bichromatic velocity-selective coherent population trapping.

PMID- 9911853
TI  - Squeezing in an optical parametric oscillator with arbitrary output mirror
      coupling: Extension to double cavities.

PMID- 9911852
TI  - Four-wave mixing in one-dimensional optical molasses.

PMID- 9911854
TI  - Displaced negative-binomial mixed states: Generalized thermo-field-dynamics.

PMID- 9911855
TI  - Propagation of mutual coherence in refractive x-ray lasers using a WKB method.

PMID- 9911857
TI  - Pump-coupled micromasers: Entangled trapping states of nonlocal fields.

PMID- 9911856
TI  - Dynamic phase of the electromagnetic field.

PMID- 9911858
TI  - Pump-coupled high-Q micromasers with conditional measurements of atoms: Transient
      and steady-state entanglement of nonlocal fields.

PMID- 9911859
TI  - Number and phase uncertainties of the q-analog quantized field.

PMID- 9911860
TI  - Pulse matching and correlation of phase fluctuations in Lambda systems.

PMID- 9911861
TI  - Quantum-nondemolition measurement of light by a piezoelectric crystal.

PMID- 9911862
TI  - Generation of sub-Poissonian and squeezed fields in the thermal superposition
      Jaynes-Cummings model.

PMID- 9911864
TI  - Quantum phase superoperator.

PMID- 9911863
TI  - Using feedback to eliminate back-action in quantum measurements.

PMID- 9911865
TI  - Effects of dissipation on nonlocal microwave fields.

PMID- 9911866
TI  - Particlelike nature of colliding three-dimensional optical solitons.

PMID- 9911867
TI  - Quantum statistics of displaced Kerr states.

PMID- 9911869
TI  - Measurements of photon statistics in second-harmonic generation.

PMID- 9911868
TI  - Fokker-Planck equation for a single two-level atom: Applications in the bad
      cavity limit.

PMID- 9911870
TI  - Interaction between a moving mirror and radiation pressure: A Hamiltonian
      formulation.

PMID- 9911872
TI  - Green function for multilayers: Light scattering in planar cavities.

PMID- 9911871
TI  - Observation of exciton-polariton oscillating emission in a single-quantum-well
      semiconductor microcavity.

PMID- 9911873
TI  - Sub-Poissonian light from a laser with an injected signal.

PMID- 9911874
TI  - Sampling entropies and operational phase-space measurement. I. General formalism.

PMID- 9911876
TI  - Cherenkov radiation emitted by solitons in optical fibers.

PMID- 9911875
TI  - Sampling entropies and operational phase-space measurement. II. Detection of
      quantum coherences.

PMID- 9911877
TI  - Elastic scattering of 88.03-keV gamma rays.

PMID- 9911878
TI  - Topological quantum phase and multipole moment of neutral particles.

PMID- 9911879
TI  - Gauge invariance and the path integral.

PMID- 9911881
TI  - Scaling of mean lifetimes of metastable molecular states with angular-momentum
      and vibrational quantum numbers.

PMID- 9911880
TI  - Relativistic corrections to the atomic electron affinities.

PMID- 9911882
TI  - Triple-differential cross section for electron-impact ionization of argon in a
      coplanar symmetric geometry at intermediate energies.

PMID- 9911883
TI  - Scattering lengths and effective ranges for He-He and spin-polarized H-H and D-D
      scattering.

PMID- 9911884
TI  - Hidden crossings and the separation constant of a hydrogenlike atom in spheroidal
      coordinates.

PMID- 9911885
TI  - Energy loss of silver ions in gadolinium.

PMID- 9911886
TI  - Energy-loss distributions for 2.5-MeV He+ ions incident on Si single crystals.

PMID- 9911887
TI  - Two-color coherent photodissociation of nitrogen oxide in intense laser fields.

PMID- 9911888
TI  - Field distribution in a generalized geometric radiation state.

PMID- 9911889
TI  - Effects of the relative coupling constants on the dynamic properties of a two
      atom system.

PMID- 9911891
TI  - Erratum: Exact Green's function for the step and square-barrier potentials

PMID- 9911890
TI  - Generation of a class of arbitrary two-mode field states in a cavity.

PMID- 9911893
TI  - Measurement of the Bell operator and quantum teleportation.

PMID- 9911894
TI  - Laser-induced collisional avalanche in atomic cesium.

PMID- 9911892
TI  - Ab initio calculation of the lifetimes of 4p and 3d levels of Ca+

PMID- 9911895
TI  - Electron-impact ionization of Na.

PMID- 9911896
TI  - High-lying doubly excited resonances in the photodetachment of H-

PMID- 9911897
TI  - Observation of enhancement of stopping power and possible hydrodynamic shock
      behavior in penetration of large molecules in solids.

PMID- 9911898
TI  - Calcium-atom interferometer comprised of four copropagating traveling laser
      beams.

PMID- 9911899
TI  - Time profile of harmonics generated by a single atom in a strong electromagnetic
      field.

PMID- 9911901
TI  - Phase-space-interference approaches to quantum superposition states.

PMID- 9911900
TI  - Observation of an electromagnetically induced change of absorption in multilevel
      rubidium atoms.

PMID- 9911902
TI  - Quantum theory of radiation-pressure fluctuations on a mirror.

PMID- 9911903
TI  - Quantum coding.

PMID- 9911904
TI  - Distributions of delay times and transmission times in Bohm's causal
      interpretation of quantum mechanics.

PMID- 9911905
TI  - Extending Schrodinger's first-passage-time probability to quantum mechanics.

PMID- 9911907
TI  - Milburn theory of decoherence using a random kicked dynamics.

PMID- 9911906
TI  - Explicit sums and integrals over complete sets of intermediate states of
      hydrogen.

PMID- 9911908
TI  - Matrix elements of two-body operators between many-body symmetrized
      hyperspherical states.

PMID- 9911910
TI  - High-resolution spectroscopy of the 1S-2S transition of atomic hydrogen and
      deuterium.

PMID- 9911909
TI  - Classical and quantum Malus laws.

PMID- 9911911
TI  - Field-induced tunneling rates, polarizabilities, and hyperpolarizabilities for
      low-lying excited states of Li and Na.

PMID- 9911912
TI  - Measurement of doubly excited levels in lithiumlike and berylliumlike cobalt.

PMID- 9911913
TI  - Coulomb holes and correlation potentials in the helium atom.

PMID- 9911914
TI  - Semiclassical computations of time-dependent tunneling.

PMID- 9911916
TI  - Bounds for the exchange and correlation potentials.

PMID- 9911915
TI  - Isotope shifts and hyperfine structure of optical transitions in 147
      150,152,154Sm II by fast-ion-beam-laser spectroscopy.

PMID- 9911918
TI  - Hyperfine splitting of the 3 (2)S state of 7Li measured using Stark spectroscopy
      of Rydberg states.

PMID- 9911917
TI  - Bounds for the atomic electronic density and related functions.

PMID- 9911919
TI  - Phase and density dependence of the delayed annihilation of metastable
      antiprotonic helium atoms in gas, liquid, and solid helium.

PMID- 9911920
TI  - Epithermal effects in muon-catalyzed dt fusion: Comparison of experimental data
      with theoretical calculations.

PMID- 9911922
TI  - Contribution of light-by-light scattering to the orders O(m alpha 8) and O(m
      alpha 8ln alpha ) orthopositronium decay rate.

PMID- 9911921
TI  - Generalized Bose-Einstein distributions and multistability of a laser-cooled gas.

PMID- 9911924
TI  - Rydberg levels of lithium.

PMID- 9911923
TI  - Precision radio-frequency measurements of the high-L Rydberg states of lithium.

PMID- 9911925
TI  - Spectrum and the softening of the proton (hole) cyclotron resonance for a
      hydrogenic atom in crossed electric and magnetic fields.

PMID- 9911926
TI  - Single-photon multiple ionization of argon in the K-edge region.

PMID- 9911927
TI  - Observation of dissociative recombination of Ne2+ and Ar2+ directly to the ground
      state of the product atoms.

PMID- 9911929
TI  - Dissociative excitation of arsenic atoms in e-As4 collisions.

PMID- 9911928
TI  - Spectroscopic properties of Mg 3pns autoionizing states.

PMID- 9911930
TI  - Electron transfer, target excitation, and ionization in H++Na(3s) and H++Na(3p)
      collisions in the coupled-Sturmian-pseudostate approach.

PMID- 9911931
TI  - Laser-induced autoionizing and continuum structures: Line-shape study in the
      presence of continuum-continuum transitions.

PMID- 9911932
TI  - Low-energy electron capture by C3+ from hydrogen using merged beams.

PMID- 9911934
TI  - s-wave positron-hydrogen scattering via Faddeev equations: Elastic scattering and
      positronium formation.

PMID- 9911933
TI  - Low-energy collisions of O5+ ions with He atoms: Single-electron capture,
      projectile excitation, and transfer excitation and ionization.

PMID- 9911935
TI  - General properties of the spectrum of complex scaled Hamiltonians: Detachment
      point and localization threshold.

PMID- 9911937
TI  - Radiative association and inverse predissociation of oxygen atoms.

PMID- 9911936
TI  - Time-ordering contributions to the product amplitude of the independent-electron
      model in double excitation.

PMID- 9911938
TI  - Photon angular distributions from radiative electron capture in relativistic
      atomic collisions.

PMID- 9911940
TI  - Two-electron ejection from helium by Compton scattering.

PMID- 9911939
TI  - Compton scattering of 20- to 40-keV photons.

PMID- 9911941
TI  - Autoionizing states of the ytterbium atom by three-photon polarization
      spectroscopy.

PMID- 9911942
TI  - Quasiclassical expression for inelastic energy losses in atomic particle
      collisions below the Bohr velocity.

PMID- 9911943
TI  - Target-thickness-dependent electron emission from carbon foils bombarded with
      swift highly charged heavy ions.

PMID- 9911944
TI  - Near-field imaging with two transmission gratings for submicrometer localization
      of atoms.

PMID- 9911946
TI  - Physical picture of photodetachment in external fields: A way to its assessment.

PMID- 9911945
TI  - Classical strong-field dissociation dynamics for linear triatomic molecules:
      Application of a coupled Morse oscillator model to HCN.

PMID- 9911947
TI  - High-order harmonic generation and above-threshold ionization in H: Calculations
      using expansions over field-free state-specific wave functions.

PMID- 9911949
TI  - Inverting the Rayleigh-Schrodinger perturbation series: Application to atomic
      stabilization by intense light.

PMID- 9911948
TI  - Coaxial-resonator-driven rf (Paul) trap for strong confinement.

PMID- 9911951
TI  - Cooling and resonance fluorescence of two atoms in a one-dimensional optical
      molasses.

PMID- 9911950
TI  - Many-body effects in near-resonant Kapitza-Dirac diffraction: The nonlinear
      Pendello-umlsung.

PMID- 9911952
TI  - Dissipative nonlinear quantum dynamics in atomic optics.

PMID- 9911953
TI  - Harmonic generation beyond the saturation intensity in helium.

PMID- 9911954
TI  - Suppression of two-photon ionization via Rydberg states.

PMID- 9911955
TI  - Group-velocity self-matching of femtosecond pulses in noncollinear parametric
      generation.

PMID- 9911957
TI  - Application of the sum-frequency generation to the vibrational spectroscopy of a
      Langmuir-Blodgett film.

PMID- 9911956
TI  - Deriving spectroscopic information from intensity-intensity correlations.

PMID- 9911958
TI  - Optical phase conjugation of nonclassical fields.

PMID- 9911959
TI  - Investigation of population inversion in Al III for amplified spontaneous
      emission at 170.

PMID- 9911960
TI  - Effects of a dye laser with correlations between additive and multiplicative
      noise: Transient properties.

PMID- 9911962
TI  - Constructive interference and efficient vacuum-ultraviolet generation in resonant
      six-wave mixing.

PMID- 9911961
TI  - Analyses of soliton interactions by means of a perturbed inverse-scattering
      transform.

PMID- 9911963
TI  - Feedback-enhanced squeezing in second-harmonic generation.

PMID- 9911965
TI  - Correlation of radiation-field ground-state fluctuations in a dispersive and
      lossy dielectric.

PMID- 9911964
TI  - Excited-state enhancement of third-order nonlinear optical responses in
      conjugated organic chains.

PMID- 9911966
TI  - Quantum dynamics of a single-atom cascade laser.

PMID- 9911967
TI  - Micromaser as a maser without inversion.

PMID- 9911969
TI  - High-order unraveling of master equations for dissipative evolution.

PMID- 9911968
TI  - Quantum theory of nonlinear fiber optics: Phase-space representations.

PMID- 9911970
TI  - Phase operators on Hilbert space.

PMID- 9911971
TI  - Enhanced squeezing due to the influence of two instabilities.

PMID- 9911972
TI  - Even and odd coherent states for multimode parametric systems.

PMID- 9911973
TI  - Variational method for approximating energy levels.

PMID- 9911974
TI  - Nonclassical effects in phase space.

PMID- 9911976
TI  - Simple example of nonlocality: Atoms interacting with correlated quantized
      fields.

PMID- 9911975
TI  - Common eigenstates of two particles' center-of-mass coordinates and mass-weighted
      relative momentum.

PMID- 9911977
TI  - Fine structure in krypton excimer.

PMID- 9911979
TI  - Retarded dipole-dipole dispersion interaction potential for helium.

PMID- 9911978
TI  - Z1 oscillations of the mean charge for isotachic ions in carbon foils.

PMID- 9911980
TI  - Cross section for the mutual neutralization reaction H2++H-, calculated in a
      multiple-crossing Landau-Zener approximation.

PMID- 9911981
TI  - Selective excitation of vibrational overtones in an anharmonic ladder with
      frequency- and amplitude-modulated laser pulses.

PMID- 9911982
TI  - Effects of imperfect unipolarity on the ionization of Rydberg atoms by
      subpicosecond half-cycle pulses.

PMID- 9911983
TI  - Light-induced drift of barium atoms.

PMID- 9911984
TI  - Radiation pressure and coherent states of two-level atoms.

PMID- 9911985
TI  - Lasing without population inversion in a simple three-level atomic system.

PMID- 9911986
TI  - Nonclassical effects and antibunching in the external photodetection of cavity
      radiation.

PMID- 9911987
TI  - Erratum: Lamb shift in the n=4 state of He+

PMID- 9911988
TI  - Erratum: Linear stochastic wave equations for continuously measured quantum
      systems

PMID- 9911989
TI  - Intrinsic and operational observables in quantum mechanics.

PMID- 9911990
TI  - Relativistic configuration-interaction analysis of parity nonconservation in Ba+

PMID- 9911991
TI  - Determination of highly excited states of diatomic-molecular ions using exact H2+
      like orbitals.

PMID- 9911992
TI  - Asymmetry parameter and total cross section for the photodetachment of the
      metastable Be- 1s22s2p24P state.

PMID- 9911993
TI  - Absolute triply differential cross sections for double photoionization of helium
      at 10, 20, and 52.9 eV above threshold.

PMID- 9911994
TI  - s-wave elastic collisions between cold ground-state 87Rb atoms.

PMID- 9911995
TI  - Breakdown of asymptotics of the double photoionization of helium at the high
      energy limit.

PMID- 9911997
TI  - Dynamics of optical-field-ionized plasmas for x-ray lasers.

PMID- 9911996
TI  - Ionization of oriented Rydberg states by subpicosecond half-cycle electromagnetic
      pulses.

PMID- 9911998
TI  - Dissociative tunnel ionization of H2 in an intense mid-ir laser field.

PMID- 9911999
TI  - Efficient quenching of population trapping in excited Yb+

PMID- 9912000
TI  - Electromagnetically induced transparency in a three-level Lambda -type system in
      rubidium atoms.

PMID- 9912001
TI  - Theory of self-phase-matching.

PMID- 9912002
TI  - Electromagnetic-field-induced transparency in high-density exciton systems.

PMID- 9912004
TI  - Why quantum dynamics can be formulated as a Markov process.

PMID- 9912003
TI  - Bell's-inequality experiment employing four harmonic oscillators.

PMID- 9912006
TI  - Analytical tests of Gutzwiller's trace formula for harmonic-oscillator
      potentials.

PMID- 9912005
TI  - Calculation of energy levels, E1 transition amplitudes, and parity violation in
      francium.

PMID- 9912007
TI  - Alternative formulation of the Wigner-Araki-Yanase theorem.

PMID- 9912008
TI  - Approximate analytic expression for the eigenenergies of the anharmonic
      oscillator V(x)=Ax6+Bx2.

PMID- 9912009
TI  - Harmonic oscillator with the radiation reaction interaction.

PMID- 9912010
TI  - Experimental tests of Bell's inequalities based on space-time and spin variables.

PMID- 9912011
TI  - Spectral geometry and the N-body problem.

PMID- 9912013
TI  - Unitary dilation models of Turing machines in quantum mechanics.

PMID- 9912012
TI  - Quantum radiative reaction on a dispersive mirror in one dimension.

PMID- 9912014
TI  - Subfemtosecond determination of transmission delay times for a dielectric mirror
      (photonic band gap) as a function of the angle of incidence.

PMID- 9912016
TI  - Hyperfine-structure studies of Nb II: Experimental and relativistic configuration
      interaction results.

PMID- 9912015
TI  - High-resolution x-ray spectroscopy of a subpicosecond-laser-produced silicon
      plasma.

PMID- 9912018
TI  - Accurate measurement of K x-ray intensities of elements with Z=79-82.

PMID- 9912017
TI  - Molecular approach for the bound states of ABA Coulomb systems from H2+ to Ps-

PMID- 9912019
TI  - X-ray observations of 2l-nl' transitions in Mo30+-Mo33+ from tokamak plasmas.

PMID- 9912020
TI  - Stark-shift measurement of the (6s)2 1S0-->(6s6p)1P1 barium transition.

PMID- 9912021
TI  - Toward understanding the exchange-correlation energy and total-energy density
      functionals.

PMID- 9912022
TI  - Exchange energy in Kohn-Sham density-functional theory.

PMID- 9912024
TI  - Formation of antihydrogen in the ground state and n=2 level.

PMID- 9912023
TI  - Modeling and efficient computation of nonlinear radiation trapping in three-level
      atomic vapors.

PMID- 9912025
TI  - Atomic transition probabilities and tests of the spectroscopic coupling scheme
      for N I.

PMID- 9912027
TI  - Classical, semiclassical, and quantum dynamics in the lithium Stark system.

PMID- 9912026
TI  - Evolution of x-ray resonance Raman scattering into x-ray fluorescence from the
      excitation of xenon near the L3 edge.

PMID- 9912028
TI  - Energy, fine-structure, and hyperfine-structure studies of the core-excited
      states 1s2s2p2(5P) and 1s2p3(5S) for Be-like systems.

PMID- 9912029
TI  - Convergence of relativistic perturbation theory for the 1s2p states in low-Z
      heliumlike systems.

PMID- 9912030
TI  - Properties of the bound S states (L=0) in Coulomb three-body systems with unit
      charges.

PMID- 9912031
TI  - Close-coupling calculation of line mixing in the isotropic Raman Q branch of D2
      in He.

PMID- 9912033
TI  - Dispersion forces between molecules with one or both molecules excited.

PMID- 9912032
TI  - K alpha hypersatellite lines of medium-mass atoms induced by 100-MeV 4He2+ ions.

PMID- 9912034
TI  - Determination of electron binding energies of ground-state dipole-bound molecular
      anions.

PMID- 9912035
TI  - Effect of a laser field on resonant photoionization and recombination processes.

PMID- 9912036
TI  - Low-energy electron capture by N4+ ions from H atoms: Experimental study using
      merged beams and theoretical analysis by molecular representation.

PMID- 9912037
TI  - Relativistic ab initio description of the K-vacancy production in heavy-ion-atom
      collision systems with solid targets.

PMID- 9912038
TI  - Energy sharing and angular distribution in the double photoionization of helium.

PMID- 9912039
TI  - Effective-potential method for relativistic electron-ion scattering.

PMID- 9912040
TI  - Wannier-ridge theory of angular distribution.

PMID- 9912041
TI  - Recoil longitudinal momentum and Q-value measurements in electron-capture
      processes of fast multiply charged ions colliding with He.

PMID- 9912043
TI  - Angular distributions in the double ionization of the noble gases by electron
      impact.

PMID- 9912042
TI  - Unexpected product fine-structure distributions in (3+1)-photon ionization of
      xenon.

PMID- 9912044
TI  - Calculation of the excitation cross sections for the 1 Sigma u+ and C 1 Pi u+
      states in e-H2 scattering at 60 eV.

PMID- 9912045
TI  - Vacuum polarization effects in low-energy muonic atom collisions.

PMID- 9912046
TI  - Electron-correlation effects in the photoionization of N2.

PMID- 9912047
TI  - Double- and triple-differential cross sections for electron-impact ionization of
      helium.

PMID- 9912049
TI  - K-shell vacancies carried by swift O and Si ions inside ferromagnetic hosts.

PMID- 9912048
TI  - Superelastic electron scattering by polarized excited sodium.

PMID- 9912050
TI  - Inner-shell vacancy distribution in energetic Ar ions by penetration in solids.

PMID- 9912051
TI  - Analytic description of the scattering of electrons by molecules.

PMID- 9912052
TI  - Accurate elastic and inelastic scattering factors from He to Ne using correlated
      wave functions.

PMID- 9912053
TI  - Rotational excitation of N2 and Cl2 molecules by electron impact in the energy
      range 0.01-1000 eV: Investigation of excitation mechanisms.

PMID- 9912054
TI  - Destruction cross sections for fast hydrogen molecules incident on helium, neon,
      and argon.

PMID- 9912055
TI  - Intramultiplet mixing in the electron-volt energy range for Ne**{(2p)5(3p)}+He.

PMID- 9912056
TI  - Long-range behavior of the optical potential for the elastic scattering of
      charged composite particles.

PMID- 9912058
TI  - Velocity dependence of KLL Auger emission from hollow atoms formed during
      collisions of hydrogenic N6+ ions on surfaces.

PMID- 9912057
TI  - Energy loss and dissociation of 10-MeV/amu H3+ ions in carbon foils.

PMID- 9912059
TI  - Measurement of the electric polarizability of sodium with an atom interferometer.

PMID- 9912061
TI  - Refractive index of a dilute Bose gas.

PMID- 9912060
TI  - Wigner-function calculations for the coherent superposition of matter waves.

PMID- 9912062
TI  - Random-matrix model for hot metallic clusters.

PMID- 9912063
TI  - Cutoff in molecular harmonic-generation spectra resulting from classical chaotic
      dynamics.

PMID- 9912064
TI  - Absorption and dispersion spectra of a polychromatic field in a two-level medium
      driven by a strong polychromatic pumping field.

PMID- 9912066
TI  - Saddle-point ionization and the Runge-Lenz invariant.

PMID- 9912065
TI  - Long lifetimes of high molecular Rydberg states in crossed magnetic and electric
      fields: An experimental and classical computational study.

PMID- 9912067
TI  - Recoil-induced resonances in pump-probe spectroscopy.

PMID- 9912068
TI  - Quantum motion of two trapped ions in one dimension.

PMID- 9912069
TI  - Atomic gravitational cavities from hollow optical fibers.

PMID- 9912070
TI  - Dipole-dipole interaction in the near-resonant Kapitza-Dirac effect.

PMID- 9912071
TI  - Selective laser-induced breakdown of xenon.

PMID- 9912072
TI  - Control of high-order harmonic generation in strong laser fields.

PMID- 9912073
TI  - Time-dependent unrestricted Hartree-Fock theory for the multiphoton ionization of
      atoms.

PMID- 9912074
TI  - Gradient force and chaotic acceleration of a dipole molecule in a standing wave.

PMID- 9912075
TI  - Multistep transitions between Rydberg states of Na induced by blackbody
      radiation.

PMID- 9912076
TI  - Strong correspondence principle and the classical-resonance overlap criterion for
      the onset of chaos.

PMID- 9912077
TI  - Doppler broadening and collisional relaxation effects in a lasing-without
      inversion experiment.

PMID- 9912079
TI  - Propagation effects and ultrafast optical switching in dense media.

PMID- 9912078
TI  - Coherent elliptic states in lithium.

PMID- 9912080
TI  - Theory of quantum-optical measurements with a phase-conjugate mirror.

PMID- 9912082
TI  - Circling optical vortices.

PMID- 9912081
TI  - Fluorescence intensity and squeezing in a driven three-level atom: Ladder case.

PMID- 9912084
TI  - Rotating patterns in class-B lasers with cylindrical symmetry.

PMID- 9912083
TI  - Noise amplification in dispersive nonlinear media.

PMID- 9912085
TI  - Moving mirrors and time-varying dielectrics.

PMID- 9912086
TI  - Spontaneous emission in planar semiconductor microcavities displaying vacuum Rabi
      splitting.

PMID- 9912087
TI  - Two-mode intelligent SU(1,1) states.

PMID- 9912088
TI  - Maxwell-Bloch formulation for semiconductors: Effects of coherent Coulomb
      exchange.

PMID- 9912089
TI  - Analogy between photorefractive oscillators and class-A lasers.

PMID- 9912092
TI  - Phase properties of Kerr media via variance and entropy as measures of
      uncertainty.

PMID- 9912091
TI  - Homodyne correlation measurements with weak local oscillators.

PMID- 9912090
TI  - Excess noise acquired by a laser beam after propagating through an atomic
      potassium vapor.

PMID- 9912093
TI  - Period-doubling cascades and chaos in a semiconductor laser with optical
      injection.

PMID- 9912094
TI  - Photon number density operator iE-circumflex

PMID- 9912096
TI  - Semiclassical study of spectral evolution under propagation in an active medium.

PMID- 9912095
TI  - Quantum-state engineering via discrete coherent-state superpositions.

PMID- 9912097
TI  - Coherent states and holomorphic representations for multilevel atoms.

PMID- 9912099
TI  - Motion of the wave-function zeros in spin-boson systems.

PMID- 9912098
TI  - Theory of amplifier-noise evasion in an oscillator employing a nonlinear
      resonator.

PMID- 9912101
TI  - Theory of optical phase conjugation in Kerr media.

PMID- 9912100
TI  - Reconstruction of the quantum state of multimode light.

PMID- 9912102
TI  - Construction of exactly soluble double-well potentials.

PMID- 9912104
TI  - Core polarization in Kr VIII.

PMID- 9912103
TI  - Heisenberg-picture approach to the exact quantum motion of a time-dependent
      harmonic oscillator.

PMID- 9912105
TI  - Variational equation of states of arbitrary angular momenta for three-particle
      systems.

PMID- 9912106
TI  - Localized states in the chaotic Ce atom.

PMID- 9912107
TI  - Charge-exchange processes between excited helium and fully stripped ions.

PMID- 9912109
TI  - Double-ring structure: Another variant in the spatial distribution of cold sodium
      atoms.

PMID- 9912108
TI  - Cross sections for the photodetachment of B-

PMID- 9912110
TI  - Spatial distortions of laser pulses in coherent on-resonance propagation: Small
      scale self-focusing.

PMID- 9912111
TI  - Comment on "Circular Rydberg orbits in circularly polarized microwave radiation"

PMID- 9912112
TI  - Erratum: Threshold effects in positron scattering on noble gases

PMID- 9912114
TI  - Convergence of diabatic to adiabatic scattering calculations.

PMID- 9912113
TI  - Molecular-orbital model for slow hollow atoms colliding with atoms in a solid.

PMID- 9912115
TI  - Interaction of fast C60 clusters with a Lindhard gas.

PMID- 9912116
TI  - Interference oscillations in ionization of extreme Stark states by half-cycle
      pulses.

PMID- 9912117
TI  - Polarization-dependent high-order two-color mixing.

PMID- 9912119
TI  - Vector gap solitons.

PMID- 9912118
TI  - Ellipticity and polarization effects in harmonic generation in ionizing neon.

PMID- 9912120
TI  - Maxwell-Bloch equations: A unified view of nonlinear optics and nonlinear atom
      optics.

PMID- 9912122
TI  - Polarization of high-intensity high-harmonic generation.

PMID- 9912121
TI  - Generation of sub-Poissonian pulses of light.

PMID- 9912124
TI  - Integration of the Heisenberg equations of motion for quartic potentials.

PMID- 9912123
TI  - Tunneling solutions of the Hamilton-Jacobi equation for multidimensional
      semiclassical theory.

PMID- 9912125
TI  - Pre- and postselected quantum systems, counterfactual measurements, and
      consistent histories.

PMID- 9912126
TI  - Reliability of one-dimensional Dirichlet wave functions.

PMID- 9912127
TI  - Quantum inverse problem for an unstable nonlinear Schrodinger equation: A
      functional Bethe ansatz.

PMID- 9912129
TI  - Quantum jumps as an objective process of nature.

PMID- 9912128
TI  - Violations of locality in polarization-correlation measurements with phase
      shifters.

PMID- 9912130
TI  - Berry phase and nonstationarity of a quantum state.

PMID- 9912131
TI  - Semirelativistic Hamiltonians of apparently nonrelativistic form.

PMID- 9912132
TI  - Geometry of one-dimensional wave propagation.

PMID- 9912133
TI  - Dependence of the rate of convergence of the Rayleigh-Ritz method on a nonlinear
      parameter.

PMID- 9912134
TI  - Thermalization of velocity-selected excited-state populations by resonance
      exchange collisions and radiation trapping.

PMID- 9912135
TI  - Isotope-shift measurement of the 6 (2)S1/2-5 (2)D5/2 transition in Ba+

PMID- 9912136
TI  - Relativistic modifications of charge expansion theory.

PMID- 9912137
TI  - Electron-impact study in valence and autoionization resonance regions of argon.

PMID- 9912138
TI  - Energy differences between Kohn-Sham and Hartree-Fock wave functions yielding the
      same electron density.

PMID- 9912139
TI  - (e-,e+)-pair annihilation in the positronium molecule Ps2.

PMID- 9912140
TI  - O( alpha 2) corrections to the orthopositronium decay rate.

PMID- 9912141
TI  - Resonances of the hydrogen atom in strong parallel magnetic and electric fields.

PMID- 9912142
TI  - Escaping the symmetry dilemma through a pair-density interpretation of spin
      density functional theory.

PMID- 9912143
TI  - Electronic bond structure of the H2+ ion in a strong magnetic field: A study of
      the parallel configuration.

PMID- 9912144
TI  - Scaled-energy spectra and closed classical orbits of the hydrogen atom in
      parallel electric and magnetic fields.

PMID- 9912145
TI  - Asymmetry parameters for CO2 around the C K and O K ionization edges from the
      anisotropy of the ion distributions.

PMID- 9912146
TI  - Measurements and data-based predictions for Delta n=1 resonance and
      intercombination transitions in the Be and Ne sequences.

PMID- 9912147
TI  - Impact of the choice of model spaces and basis sets on the performance of the
      valence-universal coupled-cluster method: Energies for Be and C2+

PMID- 9912148
TI  - Dynamic proton model for the hyperfine structure of the hydrogenlike ion
      83209Bi82+

PMID- 9912150
TI  - Multiconfiguration-Hartree-Fock calculations for the electron affinity of boron.

PMID- 9912149
TI  - Large-scale multiconfiguration Dirac-Fock calculations of hyperfine interaction
      constants for nd2 levels of Sc+ and Y+

PMID- 9912151
TI  - Master equation for sympathetic cooling of trapped particles.

PMID- 9912153
TI  - Ionization cross sections of gases for protons at kinetic energies between 20 MeV
      and 385 GeV, and applications to vacuum gauges in superconducting accelerators.

PMID- 9912152
TI  - Measurements of atomic form factors at 4.283-A-1 photon-momentum transfer.

PMID- 9912154
TI  - Effects of positive-ion resonances in photoionization of neutral atoms.

PMID- 9912155
TI  - Auger decay of Na-like Si3+(2p53lnl') states formed in slow Si5+-->He and Ar ion
      atom collisions.

PMID- 9912156
TI  - Theory of double internal bremsstrahlung during electron-capture decay.

PMID- 9912157
TI  - Off-shell effect in Rydberg-atom-alkali-metal-atom scattering.

PMID- 9912158
TI  - Relationship between the ratios of double to single ionization of helium by
      photons and charged particles.

PMID- 9912160
TI  - Ionization of excited hydrogenlike ions by collisions with bare ions.

PMID- 9912159
TI  - Resonances in photodetachment of H-(2p2 3Pe).

PMID- 9912161
TI  - Time-dependent solution of the nonlinear Schrodinger equation for Bose-condensed
      trapped neutral atoms.

PMID- 9912162
TI  - Quantum field theory of atoms interacting with photons. II. Scattering of short
      laser pulses from trapped bosonic atoms.

PMID- 9912163
TI  - Recurrences in driven quantum systems.

PMID- 9912165
TI  - Influence of barrier suppression in high-order harmonic generation.

PMID- 9912164
TI  - Pulsed NMR in terms of the statistical tensor formalism.

PMID- 9912166
TI  - Inelastic fast-electron-hydrogen-atom collision in a laser field.

PMID- 9912167
TI  - Resonances and interferences in above-threshold ionization.

PMID- 9912168
TI  - Long-term evolution and revival structure of Rydberg wave packets for hydrogen
      and alkali-metal atoms.

PMID- 9912169
TI  - Rydberg atom driven by a sequence of two laser pulses: Ramsey interferometry.

PMID- 9912170
TI  - Above-threshold multiphoton detachment of H- by two-color laser fields: Angular
      distributions and partial rates.

PMID- 9912172
TI  - Electron-atom scattering in an intense radiation field.

PMID- 9912171
TI  - Effect of random-telegraph laser phase on two-photon absorption.

PMID- 9912173
TI  - Angular momentum in harmonic generation and above-threshold ionization.

PMID- 9912175
TI  - Optical pumping of Rb vapor using high-power Ga1-xAlxAs diode laser arrays.

PMID- 9912174
TI  - Quantum interference in microwave multiphoton transitions.

PMID- 9912176
TI  - Resonances in ultracold collisions of 6Li, 7Li, and 23Na.

PMID- 9912177
TI  - From coherent to noise-induced microwave ionization of Rydberg atoms.

PMID- 9912178
TI  - Asymmetry in ionization of oriented Rydberg states of hydrogen by a half-cycle
      pulse.

PMID- 9912179
TI  - Quantum dynamics and cooling of atoms in one-dimensional standing-wave laser
      fields: Anomalous effects in Doppler cooling.

PMID- 9912180
TI  - Chaotic and regular behavior of a trapped ion interacting with a laser field.

PMID- 9912181
TI  - Spontaneous emission from stratified dielectrics.

PMID- 9912182
TI  - Raman-assisted spatial cross phase modulation in carbon disulfide.

PMID- 9912183
TI  - Macroscopic coherence via quantum feedback.

PMID- 9912184
TI  - Coherent states for four-mode systems in quantum optics.

PMID- 9912185
TI  - Orthonormalized eigenstates of the quantum operator ak and their nonclassical
      properties.

PMID- 9912186
TI  - Gap 2 pi pulse with an inhomogeneously broadened line and an oscillating solitary
      wave.

PMID- 9912188
TI  - Observation of quantum interference between dressed states in an
      electromagnetically induced transparency.

PMID- 9912187
TI  - Harmonic analysis in a large ring laser with backscatter-induced pulling.

PMID- 9912190
TI  - Destruction of photocount oscillations by thermal noise.

PMID- 9912189
TI  - Quantum state endoscopy: Measurement of the quantum state in a cavity.

PMID- 9912191
TI  - Cascaded optical cavities with two-level atoms: Steady state.

PMID- 9912192
TI  - Master-equation theory of semiconductor lasers.

PMID- 9912193
TI  - Nonlinear interaction of propagating short pulses in optically dense media.

PMID- 9912195
TI  - Geometric phase for a finite-dimensional Hilbert-space harmonic oscillator.

PMID- 9912194
TI  - Loophole-free test of the Bell inequality.

PMID- 9912196
TI  - Proposed satellite test of special relativity.

PMID- 9912197
TI  - Double-linked Hylleraas configuration-interaction calculation for the
      nonrelativistic ground-state energy of the Be atom.

PMID- 9912198
TI  - Molecular-state treatment of electron capture in slow collisions of C4+ with H:
      Alignment and orientation effects.

PMID- 9912200
TI  - Near dipole-dipole effects in electromagnetically induced transparency.

PMID- 9912199
TI  - Measurement of Ne 1s and 1snl satellite photoelectron spectra near threshold.

PMID- 9912201
TI  - Purifying a thermal field in a lossless micromaser.

PMID- 9912202
TI  - Saturation effects on intensity fluctuations of a laser with multiplicative white
      noise.

PMID- 9912203
TI  - Ring interferometer with angular acceleration.

PMID- 9912204
TI  - Comment on "Relation between the electron scattering length and the van der Waals
      approximation to the equation of state"

PMID- 9912205
TI  - Erratum: Relativistic many-body calculations of

PMID- 9912206
TI  - Measurement of the Aharonov-Casher phase of aligned Rb atoms.

PMID- 9912207
TI  - Interferences in photoexcited double-excitation series of He.

PMID- 9912208
TI  - Vibrational-state-dependent decay of the CO C(1s) excitation.

PMID- 9912209
TI  - Ultracold-molecule production by laser-cooled atom photoassociation.

PMID- 9912210
TI  - Double ionization of He and Li by 95-MeV/amu N7+ impact.

PMID- 9912211
TI  - Observation of three-level rectified dipole forces acting on trapped atoms.

PMID- 9912212
TI  - Reduced optical shielding of collisional loss for laser-cooled atoms.

PMID- 9912213
TI  - Laser cooling and the highest bound states of the Na diatom system.

PMID- 9912214
TI  - Amplification of xuv harmonic radiation in a gallium amplifier.

PMID- 9912215
TI  - Spatial position of prepulse induced J=0-->1, 3p-3s lasing in low-Z neonlike
      ions.

PMID- 9912216
TI  - Dynamical analysis of Brillouin fiber lasers: An experimental approach.

PMID- 9912217
TI  - Enhancement and suppression of optical-parametric conversion in the presence of a
      reflecting boundary.

PMID- 9912218
TI  - Conditional probabilities in quantum theory and the tunneling-time controversy.

PMID- 9912220
TI  - Puri's criterion and higher-order squeezing.

PMID- 9912219
TI  - Generalized uncertainty relations and characteristic invariants for the multimode
      states.

PMID- 9912222
TI  - delta -function bosons in a one-dimensional potential well.

PMID- 9912221
TI  - Floquet theory of bound-continuum transitions due to a periodic interaction.

PMID- 9912223
TI  - Intrinsic mechanism for entropy change in classical and quantum evolution.

PMID- 9912224
TI  - Reexamining the assumption that elements of reality can be Lorentz invariant.

PMID- 9912225
TI  - Green's functions via path integrals for systems with position-dependent masses.

PMID- 9912226
TI  - Three-level Lipkin model in the context of the suq(3) algebra.

PMID- 9912227
TI  - q analogs of the radial Schrodinger equation in N space dimensions.

PMID- 9912228
TI  - Transmission spectra for one-dimensional potentials in the semiclassical
      approximation.

PMID- 9912229
TI  - Comparison of quasiclassical and exact dipole moments for bound-free transitions
      in hydrogen.

PMID- 9912230
TI  - Interaction of the collective and electronic motion of atomic ions in magnetic
      fields.

PMID- 9912231
TI  - Interaction sites of a Na+ ion and a Na atom with a C60 molecule.

PMID- 9912232
TI  - Classical chaos and its quantum measures in Rydberg states of multielectron
      atoms.

PMID- 9912233
TI  - Laser-rf double-resonance spectroscopy of 177,179Hf.

PMID- 9912234
TI  - Fast-beam measurements of the 10D-10F fine-structure intervals in helium.

PMID- 9912235
TI  - Electron-correlation effects on the static longitudinal polarizability of
      polymeric chains.

PMID- 9912236
TI  - Monte Carlo study of population and alignment relaxation by trapped line
      radiation.

PMID- 9912237
TI  - Hyperfine structures of Ca+ and Sr+ ions: Summary of trends in hyperfine
      interactions in the alkaline-earth-metal ions and corresponding series with
      similar electronic structures.

PMID- 9912238
TI  - Polarization effects in autoionization processes: The 5d5g states in barium.

PMID- 9912240
TI  - Nonvariational calculation of the sticking probability and fusion rate for the
      microdt molecular ion.

PMID- 9912239
TI  - Pair-function calculations for two-electron systems in model plasma environments.

PMID- 9912241
TI  - Systematic multiconfiguration-Dirac-Fock study of the x-ray spectra accompanying
      the ionization in collision processes: The structure of the K beta 1,3L0Mr lines.

PMID- 9912242
TI  - Local norm-conserving pseudo-Hamiltonians.

PMID- 9912243
TI  - Thermalization of free positronium atoms by collisions with silica-powder grains,
      aerogel grains, and gas molecules.

PMID- 9912244
TI  - Relativistic configuration-interaction calculations for the n=2 states of
      lithiumlike ions.

PMID- 9912245
TI  - Collision-induced infrared absorption by H2-He complexes: Accounting for the
      anisotropy of the interaction.

PMID- 9912246
TI  - Relativistic self-interaction-free density-functional formalism.

PMID- 9912247
TI  - Transition energies of ytterbium, lutetium, and lawrencium by the relativistic
      coupled-cluster method.

PMID- 9912248
TI  - van der Waals and retardation (Casimir) interactions of an electron or an atom
      with multilayered walls.

PMID- 9912249
TI  - Dispersion forces and long-range electronic transition dipole moments of alkali
      metal dimer excited states.

PMID- 9912250
TI  - Low-energy electron collision processes in NF3.

PMID- 9912251
TI  - Enhanced charge transfer to molecular ions by electronic excitation of the
      target.

PMID- 9912252
TI  - Quantum and classical two-dimensional analysis of rainbow structures in the
      Xe+CO2 rotational excitation at 0.2 eV collision energy and on a repulsive
      potential.

PMID- 9912253
TI  - Single and double ionization of helium by intermediate-to-high-velocity He+
      projectiles.

PMID- 9912254
TI  - Double-electron detachment cross sections in intermediate-energy H- plus noble
      gas collisions.

PMID- 9912255
TI  - Resonant contributions to bound-state Compton scattering.

PMID- 9912256
TI  - Relativistic calculation of pair-production positron energy-angle distributions
      for low-energy photons on atoms.

PMID- 9912257
TI  - Electric-field effects on the N=2 Feshbach resonances of H-

PMID- 9912259
TI  - Dominant two-center electron-electron interactions in collisions of 120-MeV Ne6+
      ions with gas targets.

PMID- 9912258
TI  - Effective excitation method of a three-level medium in a selective
      photoionization.

PMID- 9912260
TI  - Method for production of a 3He beam with high polarization and high intensity.

PMID- 9912261
TI  - Total cross sections for electron scattering by polyatomic molecules at 10-1000
      eV: H2S, SiH4, CH4, CF4, CCl4, SF6, C2H4, CCl3F, CClF3, and CCl2F2.

PMID- 9912263
TI  - Absolute cross sections for the electron-impact single ionization of Mo4+ and
      Mo5+ ions.

PMID- 9912262
TI  - Electron-impact excitation of the 3 Pi u-(v=0,1,2,3; N=1) states of H2: Cross
      sections and anisotropy parameters.

PMID- 9912264
TI  - Photorecombination of highly charged uranium ions.

PMID- 9912265
TI  - Dynamic K- and L-shell filling of Ne9+ projectiles interacting with an Al(111)
      surface.

PMID- 9912266
TI  - Secondary-electron emission from porous solids.

PMID- 9912267
TI  - Monte Carlo calculations of the energy loss for H2+ molecular ions transmitted
      through thin C and Al foils.

PMID- 9912268
TI  - Multiple-cascade model for the filling of hollow Ne atoms moving below an Al
      surface.

PMID- 9912269
TI  - Angle-resolved photoelectron spectroscopy of C60.

PMID- 9912270
TI  - Influences of ac Stark shifts on coherent population trapping in the atom-field
      coupling system via Raman two-photon processes.

PMID- 9912271
TI  - General atomic response to resonant, phase-fluctuating fields in the adiabatic
      limit.

PMID- 9912272
TI  - Atomic motion in light beams possessing orbital angular momentum.

PMID- 9912273
TI  - Effect of quantum interference on the suppression of the ac Stark shifting of a
      multiphoton resonance.

PMID- 9912274
TI  - Self-induced modulation and compression of an ultracold atomic cloud in a
      nonlinear atomic cavity.

PMID- 9912275
TI  - Strong-field photoionization and emission of light in the wave-packet-spreading
      regime.

PMID- 9912277
TI  - Trapping states of motion with cold ions.

PMID- 9912276
TI  - Microwave spectroscopy of S, P, and D states of sodium Rydberg atoms.

PMID- 9912278
TI  - Role of initial coherence in the generation of harmonics and sidebands from a
      strongly driven two-level atom.

PMID- 9912280
TI  - Recoil-induced lasing of cold atoms.

PMID- 9912279
TI  - Dynamics of electronic Rydberg wave packets in isolated-core excited atoms.

PMID- 9912282
TI  - Coherent population transfer in multilevel systems with magnetic sublevels. II.
      Algebraic analysis.

PMID- 9912281
TI  - Coherent population transfer in multilevel systems with magnetic sublevels. I.
      Numerical studies.

PMID- 9912283
TI  - Generation of particles and squeezed states between moving conductors.

PMID- 9912285
TI  - Generalized Jaynes-Cummings model with random telegraph noise.

PMID- 9912284
TI  - Micromaser with stationary non-Poissonian pumping.

PMID- 9912287
TI  - Two-atom resonance fluorescence in running- and standing-wave laser fields.

PMID- 9912286
TI  - Radiative energy shifts of an accelerated two-level system.

PMID- 9912288
TI  - Stimulated Raman scattering with a Gaussian pump beam in H2 gas.

PMID- 9912289
TI  - Photorefractive ring resonators with vectorial two-beam coupling: Theory and
      applications.

PMID- 9912290
TI  - Detecting quantum superpositions of classically distinguishable states of a
      molecule.

PMID- 9912292
TI  - Asymptotically stable solitary waves in a Kerr dispersive medium in the presence
      of linear amplification and nonlinear losses.

PMID- 9912291
TI  - Amplified spontaneous emission and mirrorless lasers: Theory and experiment.

PMID- 9912294
TI  - Polarization dependence of second-harmonic generation in thin-film planar
      waveguides.

PMID- 9912293
TI  - Degenerate four-wave-mixing intensity noise fluctuations as a spectroscopic tool.

PMID- 9912295
TI  - Spontaneous emission from a three-level atom.

PMID- 9912297
TI  - Pulse propagation near highly reflective surfaces: Applications to photonic band
      gap structures and the question of superluminal tunneling times.

PMID- 9912296
TI  - Subtleties of the period-doubling chaos of an optically pumped NH3 single-mode
      ring laser.

PMID- 9912298
TI  - Optical homodyne measurements and entangled coherent states.

PMID- 9912299
TI  - Correlation-function hierarchies in nonlinear quantum optics.

PMID- 9912300
TI  - Sagnac-loop squeezer at zero dispersion with a response time for the Kerr
      nonlinearity.

PMID- 9912302
TI  - Critical fluctuations in the quantum parametric oscillator.

PMID- 9912301
TI  - Nonlinear theory of transient stimulated Raman scattering and its application to
      long-pulse experiments.

PMID- 9912303
TI  - Pattern formation in a liquid-crystal light valve with feedback, including
      polarization, saturation, and internal threshold effects.

PMID- 9912304
TI  - Coherent squeezed states of motion in an ion trap generated with Raman-driven
      sideband transitions.

PMID- 9912305
TI  - Degenerate parametric amplifiers with a squeezed pump.

PMID- 9912307
TI  - Measurement of the vibrational populations of molecular ions and its application
      to dissociative recombination in storage rings.

PMID- 9912306
TI  - Dynamical pulse shaping in a nonlinear resonator.

PMID- 9912308
TI  - Zero-order electro-optical effects in photoionization.

PMID- 9912309
TI  - l-resolved intercombination transitions in Rydberg atoms in collisions with
      electrons.

PMID- 9912310
TI  - State-selective scaling for capture to the level n=4 by multicharged ions on
      light atoms.

PMID- 9912311
TI  - Metastable-hydrogen-atom scattering by crossed beams: Total cross sections for
      H*(2s)-Ar, Xe, and CCl4 at thermal energies.

PMID- 9912312
TI  - Resonance enhancement of electron-projectile excitation in collisions of O5+ ions
      with H2 targets.

PMID- 9912313
TI  - Nuclear relaxation of 3He in the presence of O2.

PMID- 9912314
TI  - Trapping of a classical electron between two heavy scattering centers.

PMID- 9912315
TI  - Normalization of the asymptotic form of three-body (dt micro)+ and (dd micro)+
      wave functions.

PMID- 9912317
TI  - Spatial structure of light and a nonlinear refractive index generated by fanning
      in photorefractive media.

PMID- 9912316
TI  - Definition and construction of the quantum soliton states in optical fibers.

PMID- 9912318
TI  - Interference and angular distribution of transition radiation.

PMID- 9912319
TI  - Reply to "Interference and angular distribution of transition radiation"

PMID- 9912320
TI  - Erratum: Quadratic Zeeman effect in hydrogen Rydberg states: Rigorous error error
      estimates for energy eigenvalues, energy eigenfunctions, and oscillator strengths

PMID- 9912322
TI  - Low-energy electron scattering by CF4, CCl4, SiCl4, SiBr4, and SiI4.

PMID- 9912321
TI  - Erratum: Influence of relaxation phenomena in the unified description of resonant
      and nonresonant radiative transitions

PMID- 9912323
TI  - Path integrals and equations of motion for the traversal-time distributions in
      classical diffusion and quantum mechanics.

PMID- 9912324
TI  - Theory of longitudinal recoil-ion momentum distribution in ion-atom ionization.

PMID- 9912325
TI  - Guiding and trapping a neutral atom on a wire.

PMID- 9912327
TI  - Generation of coherent hard-x-ray radiation in crystalline solids by high
      intensity femtosecond laser pulses.

PMID- 9912326
TI  - Optimal control of optical pulse propagation in a medium of three-level systems.

PMID- 9912328
TI  - Generation of high-order harmonics from solid surfaces by intense femtosecond
      laser pulses.

PMID- 9912329
TI  - Formation of stable solitons in quadratic nonlinear media.

PMID- 9912330
TI  - Quon gas with the boson, fermion, and near-classical limits.

PMID- 9912331
TI  - Ermakov systems, exact solution, and geometrical angles and phases.

PMID- 9912332
TI  - q-deformed Morse oscillator.

PMID- 9912333
TI  - WKB wave functions without matching: A self-consistent procedure.

PMID- 9912334
TI  - Corrections of order alpha 2(Z alpha )5 to the hyperfine splitting and the Lamb
      shift.

PMID- 9912335
TI  - Dirac-Fock calculations for the ground states of some small molecules.

PMID- 9912336
TI  - Some identities in density-functional theory.

PMID- 9912337
TI  - Coster-Kronig yields of the 54Xe L subshells measured through synchrotron
      photoionization.

PMID- 9912338
TI  - Hierarchies of equations for the Legendre transforms of energy functionals.

PMID- 9912339
TI  - Rydberg states of HD.

PMID- 9912340
TI  - Excited electronic potential-energy surfaces and transition moments for the H3
      system.

PMID- 9912342
TI  - Electron-correlation effects on the static longitudinal polarizability of
      polymeric chains. II. Bond-length-alternation effects.

PMID- 9912341
TI  - Electronic spectrum of S2-, the electron affinity of S2, and the binding energies
      of neutral and anionic S3 clusters.

PMID- 9912343
TI  - Relativistic extension of the Bethe sum rule.

PMID- 9912344
TI  - 1/Z expansions for isoelectronic systems from He through Ar.

PMID- 9912345
TI  - Statistical theory of vibronic spectra: Envelopes of the electronic bands.

PMID- 9912346
TI  - Atomic background in x-ray absorption spectra of fifth-period elements: Evidence
      for double-electron excitation edges.

PMID- 9912347
TI  - Radiative recoil correction to the Lamb shift.

PMID- 9912348
TI  - Perturbation expansion of variational principles at arbitrary order.

PMID- 9912349
TI  - Adiabatic density-functional perturbation theory.

PMID- 9912350
TI  - Absolute partial and total cross sections for electron-impact ionization of argon
      from threshold to 1000 eV.

PMID- 9912352
TI  - Theoretical study of single and double charge transfer in He2+-He collisions at
      kilo-electron-volt energies in a diabatic molecular representation.

PMID- 9912353
TI  - Effects of a pulse width on the quantum spectra.

PMID- 9912351
TI  - L-subshell ionization of heavy elements by carbon and nitrogen ions of energy 0.4
      1.8 MeV/amu.

PMID- 9912354
TI  - Vibrationally resolved Si 2p photoabsorption spectrum of SiCl4.

PMID- 9912355
TI  - Low-energy electron collisions with sodium: Scattering of spin-polarized
      electrons.

PMID- 9912357
TI  - Six-state algebraic close-coupling calculation of positron-hydrogen scattering at
      low energies.

PMID- 9912356
TI  - Time dependence of the subexcitation electron distribution generated by high
      energy electrons.

PMID- 9912358
TI  - Elastic and inelastic processes in H++CH4 collisions in the low-kilo-electron
      volt regime.

PMID- 9912360
TI  - Search for saddle-point electrons using the continuum-distorted-wave eikonal
      initial-state model.

PMID- 9912361
TI  - Stabilized double-electron capture in Ne10+-He collisions: Velocity dependence of
      Rydberg-electron n,l distributions.

PMID- 9912362
TI  - Conjugate shake-up-enhanced Auger transitions in N2.

PMID- 9912359
TI  - Single- and double-charge-exchange cross sections for Arq++H2 (q=6, 7, 8, 9, and
      11) collisions from 6 eV to 11 keV.

PMID- 9912363
TI  - Detailed theoretical and experimental analysis of low-energy electron-N2
      scattering.

PMID- 9912364
TI  - Elastic scattering of electrons by methane molecules.

PMID- 9912365
TI  - Rotational excitation in two-center Coulomb-scattering systems: Application to
      electron-molecule collisions.

PMID- 9912367
TI  - Calculation of electron-helium scattering.

PMID- 9912366
TI  - Laser-assisted Auger decay as free-free transitions in a high-intensity laser
      field.

PMID- 9912368
TI  - Laser-induced molecular alignment in dissociation dynamics.

PMID- 9912370
TI  - Inclusion of radiation damping in the close-coupling equations for electron-atom
      scattering.

PMID- 9912369
TI  - Electron scattering from H2+: Resonances in the Sigma and Pi symmetries.

PMID- 9912371
TI  - Simplified model of electron scattering using R-matrix methods.

PMID- 9912373
TI  - Fragmentation of C60: Experimental detection of C, C2, C3, and C4 by xuv
      postionization.

PMID- 9912372
TI  - Multistep cascade model for the deexcitation of highly charged ions impinging on
      a solid surface.

PMID- 9912374
TI  - Hydrogen atoms in circularly polarized microwave fields: Near-integrability and
      ionization.

PMID- 9912375
TI  - Coherent population transfer among Rydberg states by subpicosecond, half-cycle
      pulses.

PMID- 9912376
TI  - Strong-field effects in bichromatic laser-induced collisional energy transfer.

PMID- 9912378
TI  - Photonic band gaps in optical lattices.

PMID- 9912377
TI  - Longitudinal and transverse cooling of a cesium atomic beam using the D1
      transition with Stark-effect frequency compensation.

PMID- 9912379
TI  - Theory of the two-photon autoionization of Al.

PMID- 9912380
TI  - Quantum theory of the stability region of an ion in a Paul trap.

PMID- 9912381
TI  - Phase-space density in the magneto-optical trap.

PMID- 9912382
TI  - Multiphoton Raman resonances in three-level Lambda atoms in two bichromatic
      fields.

PMID- 9912383
TI  - Asymptotic analysis in time-dependent calculations with divergent coupling.

PMID- 9912384
TI  - Probe transmission in a two-dimensional optical lattice.

PMID- 9912385
TI  - Appearance intensities for multiply charged ions in a strong laser field.

PMID- 9912386
TI  - Antiphased states in intracavity second-harmonic generation: Stability of the
      periodic solutions.

PMID- 9912387
TI  - Maxwell-Bloch system on a lattice.

PMID- 9912388
TI  - Spontaneous emission from a trapped atom.

PMID- 9912390
TI  - Quantum nondemolition measurements using a crossed Kerr effect between atomic and
      light fields.

PMID- 9912389
TI  - Entrainment of solid-state laser arrays.

PMID- 9912391
TI  - Statistical properties of a charged oscillator in the presence of a time
      dependent electromagnetic field.

PMID- 9912392
TI  - Photodetection and causality in quantum optics.

PMID- 9912393
TI  - Electromagnetic-field quantization in inhomogeneous and dispersive one
      dimensional systems.

PMID- 9912394
TI  - Effect of a squeezed vacuum input on optical bistability.

PMID- 9912395
TI  - Locking of a passive Q-switched chaotic laser system to a small external
      modulation.

PMID- 9912396
TI  - Self-tuning of dissipative solitons to the zero-dispersion point.

PMID- 9912397
TI  - Quantum coherence of optical solitons in fibers.

PMID- 9912398
TI  - Sum-frequency generation using strong-field coupling and induced transparency in
      atomic hydrogen.

PMID- 9912400
TI  - Photon echoes and Berry's phase.

PMID- 9912399
TI  - Nonclassical effects in the gray-body state.

PMID- 9912401
TI  - Two-mode quantum systems: Invariant classification of squeezing transformations
      and squeezed states.

PMID- 9912402
TI  - Dynamical properties of a classical-like entropy in the Jaynes-Cummings model.

PMID- 9912404
TI  - Spontaneous emission in the presence of a dielectric slab.

PMID- 9912403
TI  - Soft-x-ray lasing to the ground states in low-charged oxygen ions.

PMID- 9912405
TI  - Influence of spontaneous emission on trapping states and start-up times of
      degenerate two-photon micromasers.

PMID- 9912406
TI  - Quantum noise limits for nonlinear, phase-invariant amplifiers.

PMID- 9912407
TI  - Self-trapping of light beams and parametric solitons in diffractive quadratic
      media.

PMID- 9912408
TI  - Quantum images and critical fluctuations in the optical parametric oscillator
      below threshold.

PMID- 9912409
TI  - Role of standing-wave mode structure in microlaser emission.

PMID- 9912410
TI  - Higher-order squeezing in a boson-coupled two-mode system.

PMID- 9912411
TI  - Intrinsic phase operator of the Noh-Fougeres-Mandel experiments.

PMID- 9912413
TI  - Light-polarization dynamics in surface-emitting semiconductor lasers.

PMID- 9912412
TI  - Many-body theory for semiconductor microcavity lasers.

PMID- 9912414
TI  - Stimulated dynamic light scattering.

PMID- 9912415
TI  - Wave-packet localization in nonlinear external potentials with dissipation.

PMID- 9912416
TI  - Supersymmetric semiclassical approach to confined quantum problems.

PMID- 9912418
TI  - Corrections of order alpha 6 to S levels of two-body systems.

PMID- 9912417
TI  - Bound states of Ca-

PMID- 9912419
TI  - Measurement of 1s2s 3S1-1s2p 3P2,0 wavelengths in heliumlike phosphorus.

PMID- 9912420
TI  - Binding energies and nonradiative decay rates of Hed micro molecular ions.

PMID- 9912421
TI  - Some inequalities satisfied by density functionals.

PMID- 9912423
TI  - Electron correlation in double photoionization: Comparative study of secondary
      structure for Ne and Xe.

PMID- 9912422
TI  - Rotational excitation in e+-H2+ scattering.

PMID- 9912424
TI  - Wave-function overlap effects in low-energy collisional excitation of O2 by H2+,
      N2+, O2+, and CO2+ projectiles.

PMID- 9912425
TI  - Optical bistability and lasing without inversion in a system of driven two-level
      atoms with incoherent injection.

PMID- 9912426
TI  - Gain saturation and pulse statistics in single-mode semiconductor lasers.

PMID- 9912427
TI  - Origin of the lobe structure in photorefractive beam fanning.

PMID- 9912429
TI  - Optimal control of strongly driven quantum systems: Fully variational formulation
      and nonlinear eigenfields.

PMID- 9912428
TI  - Erratum: Radiative electron capture by bare and H-like Si and Cl ions using the
      channeling technique and the associated solid-state effect

PMID- 9912430
TI  - Optogalvanic study of the atomic-oxygen laser lines at 844.5 nm.

PMID- 9912431
TI  - Electron affinities of 1s22s2p 3Po and 1s22p2 3P of beryllium.

PMID- 9912433
TI  - Decoherence from spontaneous emission.

PMID- 9912432
TI  - Ionization-excitation of helium by fast charged particles.

PMID- 9912434
TI  - Measurement of the 2S1/2-2D5/2 411-nm interval in laser-cooled trapped 172Yb+
      ions.

PMID- 9912436
TI  - Nonsequential triple ionization of argon atoms in a high-intensity laser field.

PMID- 9912435
TI  - Intensity dependence of optical suppression in photoassociative ionization
      collisions in a sodium magneto-optic trap.

PMID- 9912437
TI  - Motion of laser-cooled atoms in an optical potential.

PMID- 9912438
TI  - Photon-number statistics from the phase-averaged quadrature-field distribution:
      Theory and ultrafast measurement.

PMID- 9912439
TI  - Preparation energy for electromagnetically induced transparency.

PMID- 9912440
TI  - Causality and quantization of time-delay systems: A model problem.

PMID- 9912441
TI  - Pseudomomentum conservation for one-body and two-body relativistic dynamics in a
      constant electromagnetic field.

PMID- 9912443
TI  - Eigenvalues of anharmonic oscillators and the perturbed Coulomb problem in N
      dimensional space.

PMID- 9912442
TI  - Position-dependent effective mass and Galilean invariance.

PMID- 9912444
TI  - Influence of intrinsic decoherence on nonclassical effects in the multiphoton
      Jaynes-Cummings model.

PMID- 9912446
TI  - Photon wave functions.

PMID- 9912445
TI  - Molecular Kohn-Sham exchange-correlation potential from the correlated ab initio
      electron density.

PMID- 9912447
TI  - Relativistic nuclear recoil corrections to the energy levels of hydrogenlike and
      high-Z lithiumlike atoms in all orders in alpha Z.

PMID- 9912448
TI  - Optical-rotation technique used for a high-precision measurement of parity
      nonconservation in atomic lead.

PMID- 9912449
TI  - Universal superpositions of coherent states and self-similar potentials.

PMID- 9912451
TI  - Analytic properties of the exact energy of the ground state of a two-electron
      atom as a function of 1/Z.

PMID- 9912450
TI  - Determination of radiative lifetimes of neutral bismuth by time-resolved uv-vuv
      laser spectroscopy.

PMID- 9912452
TI  - Observation of resonance line narrowing for old muonium.

PMID- 9912453
TI  - Precise experimental test of models for the breakdown of the Born-Oppenheimer
      separation: The rotational spectra of isotopic variants of lithium hydride.

PMID- 9912454
TI  - Tracking of temporal molecular data: A direct inversion algorithm for recovering
      potential energy and dipole functions.

PMID- 9912455
TI  - Finite-element-method expectation values for correlated two-electron wave
      functions.

PMID- 9912457
TI  - Alternative approach to the derivation of an expression for the cross section for
      resonant formation of dt micro in the muon-catalyzed fusion cycle.

PMID- 9912456
TI  - Role of the induced dipole moment in the collisional interference in the pure
      rotational spectrum of HD-He and HD-Ar.

PMID- 9912458
TI  - Spectroscopy of potential barriers: An analytic line-shape formula for broad
      resonances.

PMID- 9912459
TI  - Optical spectra of metal dimers and trimers in superfluid helium.

PMID- 9912460
TI  - Frequency- and time-resolved study of the dynamics of rubidium Rydberg wave
      packets in an electric field.

PMID- 9912462
TI  - Internal or shape coordinates in the n-body problem.

PMID- 9912461
TI  - Analysis of hyperspherical channels of three-electron atomic systems.

PMID- 9912464
TI  - Relativistic effects on angular distribution and polarization of dielectronic
      satellite lines of hydrogenlike ions.

PMID- 9912463
TI  - Wavelength dependence of the nonresonant photoionization cross section of a two
      electron atom near the ionization threshold.

PMID- 9912465
TI  - Electric-field effects on doubly excited states of H- between the N=3 and N=4
      thresholds of hydrogen atoms.

PMID- 9912466
TI  - Excitation mechanisms in moderate-energy Na+-Ar collisions.

PMID- 9912467
TI  - Angular distribution in the double ionization of helium by fast electrons: Effect
      of target e-e correlations.

PMID- 9912468
TI  - Chemical selectivity in the dissociative ionization of organic molecules by low
      energy positrons.

PMID- 9912470
TI  - Differential cross sections for the electron-impact excitation of hydrogenlike
      carbon.

PMID- 9912469
TI  - Shape resonances and multielectron effects in the core-level photoionization of
      CO2.

PMID- 9912471
TI  - Excitation transfer in barium by collisions with noble gases.

PMID- 9912472
TI  - Relativistic ab initio interpretation of L-K vacancy sharing in ion-solid-target
      collisions.

PMID- 9912473
TI  - Absolute cross sections for charge capture from Rydberg targets by slow highly
      charged ions.

PMID- 9912474
TI  - Nonsingular van der Waals potentials.

PMID- 9912475
TI  - Nonclassical Bose-Einstein condensate.

PMID- 9912476
TI  - Bichromatic beam splitter for three-level atoms.

PMID- 9912477
TI  - Response of metal clusters to elastic electron impact.

PMID- 9912478
TI  - Surface light-induced drift in porous media.

PMID- 9912480
TI  - Nonlinear dynamics of an atom in the quasienergy representation in the presence
      of a strongly modulated optical field.

PMID- 9912479
TI  - Potential scattering T matrix in a strong static magnetic field and a collinear
      low-frequency radiation field.

PMID- 9912481
TI  - Floquet description of multiphoton processes in Li.

PMID- 9912482
TI  - Unitary transformation and the dynamics of a three-level atom interacting with
      two quantized field modes.

PMID- 9912483
TI  - Incoherent interference control of two-photon dissociation.

PMID- 9912485
TI  - Coherent excitation of a two-state system by a train of short pulses.

PMID- 9912484
TI  - Elliptical squeezed states and Rydberg wave packets.

PMID- 9912486
TI  - Model calculations of polarization-dependent two-color high-harmonic generation.

PMID- 9912487
TI  - Short-pulse photoionization of perturbed Rydberg states: Laser-induced
      autoionization.

PMID- 9912488
TI  - Wave-packet dynamics and photoionization in the Coulomb potential.

PMID- 9912490
TI  - Continuous-wave electromagnetically induced transparency: A comparison of V,
      Lambda, and cascade systems.

PMID- 9912489
TI  - Population accumulation in dark states and subrecoil laser cooling.

PMID- 9912491
TI  - Theory on the effect of optical dephasing on spontaneous emission in
      microcavities with dispersive dielectric media.

PMID- 9912492
TI  - Jaynes-Cummings model with atomic position distribution.

PMID- 9912493
TI  - Dynamical behavior of a Brillouin fiber ring laser emitting two Stokes
      components.

PMID- 9912495
TI  - Collective-variables description of the atomic-recoil laser.

PMID- 9912494
TI  - Pair excitation-deexcitation coherent states.

PMID- 9912496
TI  - Role of pump phase fluctuations in a two-photon phase-sensitive amplifier.

PMID- 9912497
TI  - Macroscopic dynamics of a maser with non-Poissonian injection statistics.

PMID- 9912498
TI  - Spontaneous emission in non-Hermitian optical systems: Distributed-feedback
      semiconductor lasers.

PMID- 9912500
TI  - Order-disorder transitions in the dynamics of a dye laser.

PMID- 9912499
TI  - Transient macroscopic quantum superposition states in degenerate parametric
      oscillation using squeezed reservoir fields.

PMID- 9912501
TI  - Phase-sensitive reservoir modeled by beam splitters.

PMID- 9912502
TI  - Photorefractive two-wave mixing in semiconductors of the 4-bar3m space group in
      general spatial orientation.

PMID- 9912503
TI  - Propensities in discrete phase spaces: Q function of a state in a finite
      dimensional Hilbert space.

PMID- 9912504
TI  - Polarization effect in electron-excitation of hydrogen.

PMID- 9912505
TI  - Compensation of losses in photodetection and in quantum-state measurements.

PMID- 9912506
TI  - Theoretical lifetimes of Nb II z 4d3 5 (5)G3o and 3D3o levels.

PMID- 9912507
TI  - Dipole polarizabilities and hyperpolarizabilities of excited valence states of
      Be.

PMID- 9912508
TI  - Two-loop corrections to the orthopositronium and parapositronium decay rates due
      to vacuum polarization.

PMID- 9912510
TI  - Intercombination transitions in Be-like ions.

PMID- 9912511
TI  - Relative shape of the bremsstrahlung-photon energy spectrum from 7.0-keV
      electrons on Ag and Au.

PMID- 9912509
TI  - Direct computation of traces of p-order replacement operators over N-electron
      spin-adapted spaces.

PMID- 9912512
TI  - Time selection in atomic Stern-Gerlach interferometry.

PMID- 9912513
TI  - Numerical observation of stable field-supported Rydberg wave packets.

PMID- 9912514
TI  - Stroboscopic laser diagnostics for detection of ordering in a one-dimensional ion
      beam.

PMID- 9912515
TI  - Strong-field ionization of helium in the independent-electron model.

PMID- 9912516
TI  - Resonance fluorescence spectrum in a broadband squeezed vacuum: Sideband
      narrowing.

PMID- 9912518
TI  - Time-resolved nondegenerate four-wave mixing in a semiconductor amplifier.

PMID- 9912517
TI  - Quantum dynamics of a dissipative Kerr medium with time-dependent parameters.

PMID- 9912519
TI  - Modification of the completeness relation of the eigenstates of the operator ak.

PMID- 9912520
TI  - Erratum: Calculation of pair production by photons of energies near threshold on
      atoms

PMID- 9912522
TI  - Homodyne detection of the density matrix of the radiation field.

PMID- 9912521
TI  - Erratum: Theoretical charge-exchange Galilean invariant cross sections for the
      B3++He collision

PMID- 9912523
TI  - Expression of the exact electron-correlation-energy density functional in terms
      of first-order density matrices.

PMID- 9912524
TI  - Correlation-energy density-functional formulas from correlating first-order
      density matrices.

PMID- 9912525
TI  - Classical theory of l-changing transitions in collisions between Rydberg atoms
      and ions.

PMID- 9912526
TI  - Direct observation of correlation between electron emission and fragmentation
      into ions following B 1s excitation of the BF3 molecule.

PMID- 9912527
TI  - Probe-transmission spectrum of a blue-detuned optical lattice.

PMID- 9912528
TI  - Transparency and dressing for optical pulse pairs through a double- Lambda
      absorbing medium.

PMID- 9912530
TI  - Hardy's approach, Eberhard's inequality, and supplementary assumptions.

PMID- 9912529
TI  - Experimental evidence for nonclassical fourth-order interferences in the
      quasielastic light scattering of water.

PMID- 9912532
TI  - Geometric phases in two-photon interference experiments.

PMID- 9912531
TI  - Time-symmetric formulation of quantum mechanics.

PMID- 9912533
TI  - Stability of systems of three arbitrary charges: General properties.

PMID- 9912534
TI  - Complete algebraization of quantum mechanics in terms of quantum groups and
      noncommutative geometry, and q-implicate order.

PMID- 9912535
TI  - Casimir torque between dielectrics.

PMID- 9912536
TI  - Geometric aspects of noncyclic quantum evolutions.

PMID- 9912537
TI  - Algebraic approach to the Jaynes-Cummings models.

PMID- 9912538
TI  - Interference, distinguishability, and apparent contradiction in an experiment on
      induced coherence.

PMID- 9912539
TI  - Reshaping, path uncertainty, and superluminal traveling.

PMID- 9912540
TI  - Quantum inference methods and hypervirial theorems.

PMID- 9912542
TI  - Motion and ionization equilibrium of hydrogen atoms in a superstrong magnetic
      field.

PMID- 9912541
TI  - First ionization potential of platinum by mass-selected double-resonance field
      ionization spectroscopy.

PMID- 9912544
TI  - Electron affinities and hyperfine structure for U- and U I obtained from
      relativistic configuration-interaction calculations.

PMID- 9912543
TI  - Intramolecular dynamics from a statistical analysis of vibrational levels:
      Application of two coupled Morse oscillator models to the HCN molecule.

PMID- 9912545
TI  - Effect of positive-energy orbitals on the photoionization cross sections and
      oscillator strengths of He and divalent atoms.

PMID- 9912546
TI  - Cusp relations for local strongly decaying properties in electronic systems.

PMID- 9912547
TI  - H2-He vibrational line-shape parameters: Measurement and semiclassical
      calculation.

PMID- 9912548
TI  - Precision measurement of the 1S ground-state Lamb shift in atomic hydrogen and
      deuterium by frequency comparison.

PMID- 9912549
TI  - Measurements of the resonance lines of 6Li and 7Li by Doppler-free frequency
      modulation spectroscopy.

PMID- 9912550
TI  - Measurements of line overlap for resonant spoiling of x-ray lasing transitions in
      nickel-like tungsten.

PMID- 9912551
TI  - Structure and Lamb shift of 2s1/2-2p3/2 levels in lithiumlike Th87+ through
      neonlike Th80+

PMID- 9912552
TI  - Optical properties of alkali-metal atoms in pressurized liquid helium.

PMID- 9912553
TI  - Experimental observation of the lowest 1 Sigma u+ valence state of O2.

PMID- 9912554
TI  - All-electron relativistic Dirac-Fock-Slater self-consistent-field calculations of
      the singly charged diatomic transition-metal- (Fe, Co, Ni, Cu, Zn) argon
      molecules.

PMID- 9912555
TI  - Photodetachment of H- and Li-

PMID- 9912557
TI  - Transition energies of mercury and ekamercury (element 112) by the relativistic
      coupled-cluster method.

PMID- 9912556
TI  - Local and nonlocal relativistic exchange-correlation energy functionals:
      Comparison to relativistic optimized-potential-model results.

PMID- 9912558
TI  - Atomic energy levels and Lande g factors: A theoretical study.

PMID- 9912560
TI  - Spectrum-generating algebra for X3 molecules.

PMID- 9912559
TI  - Change of variables for fully numerical electronic-structure calculations that
      concentrates the grid points in the atomic-core regions and is adequate for fast
      Fourier transforms.

PMID- 9912561
TI  - High-resolution study of the K beta 2 x-ray spectra induced by proton and photon
      impact on Zr, Mo, and Pd targets.

PMID- 9912563
TI  - Interelectronic interaction contribution to the hyperfine structure of highly
      charged lithiumlike ions.

PMID- 9912562
TI  - Effects of temperature on the absorption line-shape function for driven two-level
      atoms: A non-Markovian treatment.

PMID- 9912564
TI  - Auger-electron spectroscopy of molecules: Circular dichroism in angular
      correlation with photoelectrons from rotating linear molecules.

PMID- 9912566
TI  - Resonant dipole-dipole interaction in a cavity.

PMID- 9912565
TI  - Effect of Compton scattering on the double-to-single photoionization ratio in
      helium.

PMID- 9912567
TI  - Photodetachment study of B- ions: The influence of the first excited boron state.

PMID- 9912569
TI  - Formation of antihydrogen by the charge-transfer reaction.

PMID- 9912568
TI  - Ionization and charge transfer in collisions of highly charged ions with helium
      at low velocity.

PMID- 9912571
TI  - Pair-production positron energy-angle distributions of 5mec2 and 10mec2 photons
      on atoms.

PMID- 9912570
TI  - Floquet analysis of inelastic collisions of ions with Rydberg atoms.

PMID- 9912573
TI  - Coherent excitation of the singlet-triplet mixed 1s4f state of helium.

PMID- 9912572
TI  - Resonant effects on electron-impact ionization of sodiumlike selenium.

PMID- 9912574
TI  - Dissociative recombination of H2D+: Cross sections, branching fractions, and
      isotope effects.

PMID- 9912576
TI  - Retardation effects and angular coefficients in double photoionization.

PMID- 9912575
TI  - Recombination in Kr34++H2 collisions.

PMID- 9912577
TI  - Correlated-state evaluation of the second virial coefficient.

PMID- 9912579
TI  - Observation of anomalous behavior of the Xe 4d photoelectron satellites.

PMID- 9912578
TI  - General properties of the spectrum of complex scaled Hamiltonians: The transition
      to two dimensions.

PMID- 9912580
TI  - Convergence acceleration for the Kohn variational method in the presence of a
      long-range interaction.

PMID- 9912581
TI  - Target-electronic-structure dependence in highly-charged-ion-C60 collisions.

PMID- 9912582
TI  - Two-ion superradiance theory.

PMID- 9912583
TI  - Theoretical study of photoelectron angular distribution in (1+1('))-photon
      resonance-enhanced multiphoton ionization of the H2 molecule.

PMID- 9912584
TI  - Dissociation, ionization, and Coulomb explosion of H2+ in an intense laser field
      by numerical integration of the time-dependent Schrodinger equation.

PMID- 9912585
TI  - Multiphoton fragmentation of H2+ and D2+ with coherent and incoherent fields.

PMID- 9912587
TI  - High-order harmonic generation in the tunneling regime.

PMID- 9912586
TI  - Transient internal dynamics of a multilevel ion.

PMID- 9912588
TI  - Noise-induced fluctuations in two-ion systems driven by light beams.

PMID- 9912589
TI  - Subrecoil cooling of Rydberg atoms.

PMID- 9912590
TI  - Off-resonance light scattering from low-temperature Bose and Fermi gases.

PMID- 9912591
TI  - Rydberg transitions induced by optical core dressing.

PMID- 9912592
TI  - Effect of spontaneous emission on the atomic modes in a stable gravitational
      cavity.

PMID- 9912593
TI  - Nonlinear resonance and dynamical chaos in a diatomic molecule driven by a
      resonant ir field.

PMID- 9912594
TI  - Ultrafast pulse interactions with two-level atoms.

PMID- 9912595
TI  - Observation of dark photovoltaic spatial solitons.

PMID- 9912596
TI  - Three-level nonlinear selective reflection at a glass-Cs-vapor interface.

PMID- 9912597
TI  - From amplification of spontaneous emission to saturation in x-ray lasers: A
      Maxwell-Bloch treatment.

PMID- 9912599
TI  - Coherent population trapping at low light levels.

PMID- 9912598
TI  - Probability distribution of photoelectric currents in photodetection processes
      and its connection to the measurement of a quantum state.

PMID- 9912600
TI  - Competing interactions and quantum nonspreading wave packets.

PMID- 9912601
TI  - Two-photon spectroscopy: A technique for characterizing diode-laser noise.

PMID- 9912602
TI  - Families of multiwavelength spatial solitons in nonlinear Kerr media.

PMID- 9912603
TI  - CO2 laser dynamics with feedback.

PMID- 9912604
TI  - Field dynamics, instabilities, and phase squeezing in the two-photon correlated
      emission laser.

PMID- 9912605
TI  - Phase coherence and decoherence in the correlated-spontaneous-emission laser.

PMID- 9912607
TI  - Effect of the pump state on the dynamics of the parametric amplifier.

PMID- 9912606
TI  - Effect of Doppler broadening on optical gain without inversion in a four-level
      model.

PMID- 9912609
TI  - Lasing without inversion in the absence of a coherent coupling field.

PMID- 9912608
TI  - Coherence-induced population redistribution in optical pumping.

PMID- 9912611
TI  - Sub-Poisson photoelectron statistics in saturated light absorption.

PMID- 9912610
TI  - Nonlinear pulse propagation in the vicinity of a two-photon resonance.

PMID- 9912612
TI  - Self-focused light propagation in a fully saturable medium: Theory.

PMID- 9912613
TI  - (3+1)-dimensional optical soliton dragging logic.

PMID- 9912614
TI  - Two-mode Lambda laser with atoms injected in a superposition of their states.

PMID- 9912615
TI  - Phase operator for the photon field and an index theorem.

PMID- 9912616
TI  - Superfluorescence in a continuously pumped medium.

PMID- 9912617
TI  - Bistability in a quantum nonlinear oscillator.

PMID- 9912619
TI  - Spectral structures induced by electron shelving.

PMID- 9912618
TI  - Effect of dissipation and measurement on a tunneling system.

PMID- 9912621
TI  - Analysis of the Dirac-Coulomb problem in the free-particle representation.

PMID- 9912620
TI  - Tunable Bell-inequality violations by non-maximally-violating states in type-II
      parametric down-conversion.

PMID- 9912622
TI  - Exact wave functions and nonadiabatic Berry phases of a time-dependent harmonic
      oscillator.

PMID- 9912623
TI  - Square root of the harmonic oscillator.

PMID- 9912624
TI  - Corrections of order alpha 3(Z alpha )4 and alpha 2(Z alpha )6 to the Lamb shift.

PMID- 9912625
TI  - Hyperspherical adiabatic approach for the helium atom.

PMID- 9912626
TI  - Electron-impact excitation of heliumlike titanium.

PMID- 9912627
TI  - Eliminating cold-collision frequency shifts.

PMID- 9912628
TI  - Theorem on nonclassical states.

PMID- 9912629
TI  - Comment on "Perturbation expansion of closed-time-path Green's functions"

PMID- 9912630
TI  - Reply to "Comment on 'Perturbation expansion of closed-time-path Green's
      functions' "

PMID- 9912631
TI  - Comment on "Reliability of Bell-inequality measurements using polarization
      correlations in parametric-down-conversion photon sources"

PMID- 9912633
TI  - Proposed test for realist theories using Rydberg atoms coupled to a high-Q
      resonator.

PMID- 9912632
TI  - Scheme for reducing decoherence in quantum computer memory.

PMID- 9912635
TI  - Molecular treatment of H++He+(1s) collisions including pseudostates.

PMID- 9912634
TI  - Threshold ionization dynamics of the hydrogen atom in crossed electric and
      magnetic fields.

PMID- 9912636
TI  - Laser spectroscopy of the Be- ion: Binding energies of metastable states.

PMID- 9912638
TI  - Buffer-gas loading of atoms and molecules into a magnetic trap.

PMID- 9912637
TI  - Charge-resonance-enhanced ionization of diatomic molecular ions by intense
      lasers.

PMID- 9912640
TI  - Classical aspects of quantum localization in microwave ionization of H atoms.

PMID- 9912639
TI  - Recoil-induced optical Faraday rotation.

PMID- 9912641
TI  - High-intensity two-color interactions in the tunneling and stabilization regimes.

PMID- 9912642
TI  - Brillouin scattering and dynamical diffraction of entangled photon pairs.

PMID- 9912643
TI  - Approach to a generalized Jaynes-Cummings model and the geometric phase.

PMID- 9912644
TI  - Dynamics on a rotating disk.

PMID- 9912645
TI  - Elementary gates for quantum computation.

PMID- 9912646
TI  - Extension of a moment-problem minimax quantization procedure to anharmonic
      potentials.

PMID- 9912647
TI  - Number-phase Wigner function on Fock space.

PMID- 9912648
TI  - Simple quantum computer.

PMID- 9912649
TI  - Periodic orbits of the hydrogen molecular ion and their quantization.

PMID- 9912650
TI  - Randomness, nonlocality, and information in entangled correlations.

PMID- 9912651
TI  - Weakly bound three-body systems with no bound subsystems.

PMID- 9912652
TI  - Limit on the electric-dipole moment of 199Hg using synchronous optical pumping.

PMID- 9912653
TI  - Interference and transmission of quantum fluxons through a Josephson ring.

PMID- 9912654
TI  - Transfer-matrix approach to tunneling between Kolmogorov-Arnold-Moser tori.

PMID- 9912656
TI  - Using classical probability to guarantee properties of infinite quantum
      sequences.

PMID- 9912655
TI  - Simple cavity-QED two-bit universal quantum logic gate: The principle and
      expected performances.

PMID- 9912657
TI  - Relativistic calculations of the hyperfine interactions in the excited 7 2P3/2
      and 7 2P1/2 states of the Ra+ ion.

PMID- 9912659
TI  - Measurement of two-electron contributions to the ground-state energy of
      heliumlike ions.

PMID- 9912658
TI  - Probing symmetry breaking upon core excitation with resonant x-ray fluorescence.

PMID- 9912660
TI  - Effect of quantum-mechanical symmetry on the geometric structures of intrashell
      states of three-valence-electron atoms.

PMID- 9912661
TI  - Forward-scattering magneto-optical effects.

PMID- 9912662
TI  - Time-dependent density-matrix functional in Liouville space and the optical
      response of many-electron systems.

PMID- 9912663
TI  - Relativistic many-body effects in the fine and hyperfine structure of 139La II
      (5d+6s)2 J=2 states: The need for second-order electrostatic corrections.

PMID- 9912664
TI  - Electron density near the nucleus of a large atom.

PMID- 9912666
TI  - Measurement of the radiative lifetime of the 1s2s 3S1 level in heliumlike
      magnesium.

PMID- 9912667
TI  - Cross correlations in Ramsey pump-probe interferometry.

PMID- 9912665
TI  - High-resolution measurements of Mg XI and Cu XX resonance and satellite
      transitions and the resonance defect in the Mg-pumped Cu x-ray laser scheme.

PMID- 9912669
TI  - Energies and lifetimes of triply excited states of lithium.

PMID- 9912668
TI  - L2,3 and M2,3 level widths and fluorescence yields of copper.

PMID- 9912670
TI  - Determination of dipole polarizabilities for Mg+ and Ca+ ions from precision
      lifetime measurements and transition-moment cancellations.

PMID- 9912671
TI  - Asymptotic-expansion method for the evaluation of correlated three-electron
      integrals.

PMID- 9912672
TI  - Hyperfine structure of hydrogenlike and lithiumlike atoms.

PMID- 9912674
TI  - Recurrences associated with a classical orbit in the node of a quantum wave
      function.

PMID- 9912673
TI  - Dispersion of the refractive index of cadmium vapor and the dipole polarizability
      of the atomic cadmium 1S0 state.

PMID- 9912675
TI  - Gradient-corrected exchange potential with the correct asymptotic behavior and
      the corresponding exchange-energy functional obtained from the virial theorem.

PMID- 9912676
TI  - Eigenvalues and expectation values for the 1s22s 2S, 1s22p 2P, and 1s23d 2D
      states of lithium.

PMID- 9912677
TI  - Modified configuration-interaction method.

PMID- 9912679
TI  - Soft-electron-peak asymmetry.

PMID- 9912678
TI  - Sub-electron-volt chemical shifts and strong interference effects measured in the
      resonance x-ray scattering spectra of aniline.

PMID- 9912680
TI  - Modeling of metastable argon atoms in a direct-current glow discharge.

PMID- 9912682
TI  - Lifetime, collisional-quenching, and j-mixing measurements of the metastable 3D
      levels of Ca+

PMID- 9912681
TI  - Time-dependent approach to electron scattering and ionization in the s-wave
      model.

PMID- 9912683
TI  - Dielectronic recombination of Ni-like ions through the 3d94ln'l' (n'=4,5) Cu-like
      configurations.

PMID- 9912684
TI  - Exact treatment of reactive scattering in the Torres-Vega-Frederick quantum phase
      space representation.

PMID- 9912685
TI  - Effects of autoionizing resonances on electron-impact excitation rates and gain
      calculations for Ni-like tantalum.

PMID- 9912686
TI  - Two-center electron emission in collisions of fast, highly charged ions with He:
      Experiment and theory.

PMID- 9912687
TI  - Polarization of lines emitted after electron capture into Ar7+(nlml) sublevels
      during 80-keV Ar8+-Li collisions.

PMID- 9912689
TI  - Experimental determination of the real elements of the density matrix of H(n=3)
      atoms produced in 20-100-keV collisions of H+ on Kr.

PMID- 9912688
TI  - Absolute cross sections for the dipole-allowed transitions 30s-30p and 29d-30p in
      collisions between charged particles and Na Rydberg atoms.

PMID- 9912690
TI  - Levinson-Seaton theorem for potentials with an attractive Coulomb tail.

PMID- 9912691
TI  - Relativistic collision strengths for optically allowed Delta n=0 transitions
      between magnetic sublevels of highly charged ions.

PMID- 9912692
TI  - Absolute cross-section measurements for ionization of He Rydberg atoms in
      collisions with K.

PMID- 9912693
TI  - Charge-state dependence of M-shell x-ray production in 67Ho by 2-12-MeV carbon
      ions.

PMID- 9912694
TI  - Fullerene-fullerene collisions: Fragmentation and electron capture.

PMID- 9912695
TI  - Radiative damping and interference in the resonance structure of the electron
      impact excitation cross sections for Ti20+

PMID- 9912696
TI  - Comparison of eikonal and multiple-scattering representations of internuclear
      scattering in charge transfer at forward angles.

PMID- 9912697
TI  - Direct solution of the time-dependent Schrodinger equation for proton-hydrogen
      collisions in two-dimensional Cartesian space.

PMID- 9912698
TI  - Elimination of electron-ion pseudoresonances associated with approximate target
      wave functions.

PMID- 9912699
TI  - Probabilities for L-shell ionization in intermediate-velocity collisions of
      medium-mass elements with 4He2+ ions.

PMID- 9912701
TI  - Distribution of electrons in double photoionization of helium and heavier atoms
      in the asymptotic region.

PMID- 9912700
TI  - Thomas double scattering in electron capture from oriented molecular hydrogen.

PMID- 9912702
TI  - Extended Gel'fand-Levitan method leading to exactly solvable Schrodinger
      equations with generalized Bargmann potentials.

PMID- 9912703
TI  - Scattering from a shifted von Neumann-Wigner potential.

PMID- 9912704
TI  - Angular distributions of selected N2 Auger transitions.

PMID- 9912706
TI  - Electronic stopping of low- and intermediate-energy protons in solids.

PMID- 9912705
TI  - Spheroidal analysis of the angular distribution of Auger electrons emitted by
      homonuclear diatomic molecules.

PMID- 9912707
TI  - Electron-emission yield of Al, Cu, and Au for the impact of swift bare light
      ions.

PMID- 9912709
TI  - Index of refraction of dilute matter in atomic interferometry.

PMID- 9912708
TI  - Theoretical and experimental study of the Bragg scattering of atoms from a
      standing light wave.

PMID- 9912710
TI  - Intensity-dependent atomic-phase effects in high-order harmonic generation.

PMID- 9912711
TI  - Two-color phase control of high-order harmonic generation in intense laser
      fields.

PMID- 9912712
TI  - Schrodinger modal structure of cubical, pyramidal, and conical, evanescent light
      wave gravitational atom traps.

PMID- 9912713
TI  - Microscopic magnetic traps for neutral atoms.

PMID- 9912715
TI  - Adiabatic transition histories of population transfer in the Lambda system.

PMID- 9912714
TI  - Theoretical investigation of two-color, two-photon, 6s 2S1/2-->5d 2Dj-->11p 2P3/2
      excitation and depolarization spectra in atomic Cs.

PMID- 9912716
TI  - Quantum signatures in the stabilization dynamics.

PMID- 9912717
TI  - Optical collisions in ultracold atom traps: Two-photon distorted-wave theory.

PMID- 9912719
TI  - Steering of bright-soliton pairs excited by symmetric and real initial profiles.

PMID- 9912720
TI  - Two-photon laser dynamics.

PMID- 9912718
TI  - Classical rescattering effects in two-color above-threshold ionization.

PMID- 9912721
TI  - Nonlinear refractive index near points of zero absorption and in the dead zone.

PMID- 9912722
TI  - Theoretical scheme for lasing without population inversion in the H2 molecule.

PMID- 9912723
TI  - Photon-hopping conduction and collectively induced transparency in a photonic
      band gap.

PMID- 9912725
TI  - Modification of a vacuum Rabi splitting via a frequency-modulated cavity mode.

PMID- 9912724
TI  - Theory of phase locking of globally coupled laser arrays.

PMID- 9912726
TI  - Stability of scalar spatial solitons in cascadable nonlinear media.

PMID- 9912728
TI  - Optical third-harmonic generation at interfaces.

PMID- 9912727
TI  - Efficient route to saturation in collisionally pumped, soft-x-ray lasers.

PMID- 9912729
TI  - Asymmetric probe-absorption spectrum and amplification without population
      inversion in a squeezed vacuum.

PMID- 9912730
TI  - Minimal equations for antiphase dynamics in multimode lasers.

PMID- 9912731
TI  - Nonlocal cancellation of dispersive broadening in Mach-Zehnder interferometers.

PMID- 9912733
TI  - Diode-laser-noise-based spectroscopy of allowed and crossover resonances.

PMID- 9912732
TI  - Noise-free amplification of squeezed light via atomic coherence.

PMID- 9912734
TI  - Analysis of total-internal-reflection phase-conjugate mirror.

PMID- 9912735
TI  - Amplitude equations and pattern formation in a liquid-crystal light-valve
      experiment.

PMID- 9912736
TI  - Dark-soliton timing jitter caused by fluctuations in initial pulse shape.

PMID- 9912737
TI  - Turn-on-time statistics of modulated lasers subjected to resonant weak optical
      feedback.

PMID- 9912738
TI  - Photon statistics in spontaneous emission for the Dicke model in a lossless
      cavity and the generation of the Fock state.

PMID- 9912739
TI  - Ultrashort pulsed squeezing by optical parametric amplification.

PMID- 9912741
TI  - Beam self-focusing in the presence of a small normal time dispersion.

PMID- 9912740
TI  - Nonlinear Jaynes-Cummings dynamics of a trapped ion.

PMID- 9912742
TI  - Polarization instability in lasers. I. Model and steady states of neodymium-doped
      fiber lasers.

PMID- 9912743
TI  - Polarization instability in lasers. II: Influence of the pump polarization on the
      dynamics.

PMID- 9912744
TI  - Bound quantum states with no classical turning points.

PMID- 9912745
TI  - Exactness of the broken supersymmetric, semiclassical quantization rule.

PMID- 9912746
TI  - Multiconfiguration Hartree-Fock calculations of low-lying excited 2S states in
      lithium.

PMID- 9912747
TI  - Laser-induced resonant transition at 470.724 nm in the v=n-l-1=2 cascade of
      metastable antiprotonic helium atoms.

PMID- 9912749
TI  - Theoretical calculation of dielectronic recombination cross sections for
      hydrogenlike helium.

PMID- 9912748
TI  - Nearly normalized, distorted strong-potential Born state vector.

PMID- 9912750
TI  - Phase and intensity control of integral and differential above-threshold
      ionization rates.

PMID- 9912751
TI  - Nonlinear dynamics of the Kingdon equation.

PMID- 9912752
TI  - Nonspreading Rydberg wave packets supported by a linearly polarized
      electromagnetic field.

PMID- 9912754
TI  - Squeezed vacuum as an accelerator of revivals in the Dicke model.

PMID- 9912753
TI  - Time evolution of a hydrogen atom in a strong, ultrashort, high-frequency laser
      pulse.

PMID- 9912756
TI  - Erratum: Semiclassical multichannel perturbed-stationary-state model for
      rearrangement atomic collisions

PMID- 9912755
TI  - There is no classical analog of a quantum time-translation machine.

PMID- 9912757
TI  - Effective disappearance of degenerating energy levels.

PMID- 9912758
TI  - Nonperturbative behavior of a hydrogen atom in a van der Waals field.

PMID- 9912759
TI  - Grid-free density-functional technique with analytical energy gradients.

PMID- 9912760
TI  - Isotopic effect of the mean lifetimes of the NeAr2+ doubly charged rare-gas
      dimer.

PMID- 9912761
TI  - Ground state of a hydrogen molecule in superstrong magnetic fields.

PMID- 9912762
TI  - Observation of the Ar2+(3s23p3nl) satellite states by threshold photoelectrons
      coincidence (TPEsCO) spectroscopy.

PMID- 9912764
TI  - Adiabatic climbing of vibrational ladders using Raman transitions with a chirped
      pump laser.

PMID- 9912763
TI  - Double photoionization of helium at low photon energies.

PMID- 9912765
TI  - Observation of a transient response of recoil-induced resonance: A method for the
      measurement of atomic motion in an optical standing wave.

PMID- 9912767
TI  - Optical imaging by means of two-photon quantum entanglement.

PMID- 9912766
TI  - Three-dimensional cooling of cesium atoms in four-beam gray optical molasses.

PMID- 9912768
TI  - Ne-like ion lasers in the extreme ultraviolet region.

PMID- 9912769
TI  - Diode lasers with optical feedback: Stability of the maximum gain mode.

PMID- 9912770
TI  - Generation of transient Rabi sidebands in pulse propagation: A possible source
      for cone emission.

PMID- 9912771
TI  - Collision of solitary waves in media with a second-order nonlinearity.

PMID- 9912772
TI  - Number-phase uncertainty product for generalized squeezed states arising from the
      Pegg-Barnett Hermitian phase operator formalism.

PMID- 9912773
TI  - Semiclassical expansion theory in phase space.

PMID- 9912774
TI  - Causality and quantization of time-delay systems: A two-body model problem.

PMID- 9912775
TI  - Proposal for a loophole-free test of the Bell inequalities.

PMID- 9912777
TI  - Radiation modes of a cavity with a moving boundary.

PMID- 9912776
TI  - Description of entanglement.

PMID- 9912778
TI  - Perturbed 5snd 1,3D2 Rydberg series of Sr.

PMID- 9912779
TI  - xuv-laser spectroscopy of HD at 92-98 nm.

PMID- 9912780
TI  - Hyperfine-structure measurements in the ground state of radioactive 150Eu+ ions.

PMID- 9912781
TI  - Stark-induced anapole magnetic fields in atoms.

PMID- 9912782
TI  - Hyperfine-structure measurements in the 4p 2P3/2 state of 41K using polarization
      quantum-beat spectroscopy.

PMID- 9912783
TI  - Absolute measurements of optical oscillator strengths of noble-gas resonance
      lines.

PMID- 9912785
TI  - Fourier-transform-spectroscopy measurements in the spectra of neutral lithium,
      6Li

PMID- 9912784
TI  - Charge-transfer-induced multiplet structure in the N4,5O2,3 soft-x-ray emission
      spectrum of lanthanum.

PMID- 9912786
TI  - Problem of two fixed centers and a finite dipole: A unified treatment.

PMID- 9912788
TI  - Explicitly correlated Gaussian functions in variational calculations: The ground
      state of the beryllium atom.

PMID- 9912787
TI  - Hardness of molecules and the band gap of solids within the Kohn-Sham formalism:
      A perturbation-scaling approach.

PMID- 9912790
TI  - Static-field effects on the nonlinear quantum resonances and the ionization
      spectrum of a simple bound particle.

PMID- 9912789
TI  - Calculation of the energy levels of a hydrogen atom in a magnetic field of
      arbitrary strength by using B splines.

PMID- 9912791
TI  - Self-consistent effective particle-hole interaction in the Lipkin model.

PMID- 9912792
TI  - Bound states of positrons and neutral atoms.

PMID- 9912793
TI  - Electric-field-induced electron detachment of 800-MeV H- ions.

PMID- 9912794
TI  - Dissociative recombination studies of Ar2+ by time-of-flight spectroscopy.

PMID- 9912795
TI  - Interference effects in the autoionization of 4f7h and 6dni states of barium.

PMID- 9912796
TI  - Multiple-electron ionization, capture, and loss by 19-MeV Fq+ (q=2-9) in
      collisions with Ne and Ar.

PMID- 9912798
TI  - Threshold behavior in single-photon double ionization of atomic oxygen.

PMID- 9912797
TI  - Autoionization of the J=2 and J=4 3pnf states of magnesium.

PMID- 9912799
TI  - Electron spin exchange with O2: Effects on the muon spin rotation, the electron
      spin resonance, and the positronium lifetime.

PMID- 9912800
TI  - Electron capture by fully stripped high-Z projectiles from the hydrogen atom.

PMID- 9912801
TI  - H2 doubly-excited-state assignment from the determination of the orbital state of
      the H*(n=3) photodissociation fragments.

PMID- 9912803
TI  - Excess photon ionization and harmonic generation through an autoionizing
      resonance.

PMID- 9912802
TI  - Observation of beam-induced changes in the polarization of Balmer- alpha
      radiation emitted following beam-tilted-foil transmission.

PMID- 9912804
TI  - Intra-atomic relativistic effects on the spin polarization in low-energy electron
      scattering from Ca, Sr, Ba, and Yb atoms.

PMID- 9912805
TI  - Photoionization of atomic oxygen at the multiplet term level from 20 to 212 eV.

PMID- 9912806
TI  - Electron-impact core excitation of SF6. I. S 2p, S 2s, and F 1s spectroscopy.

PMID- 9912807
TI  - Electron-impact core excitation of SF6. II. Generalized oscillator strengths in
      the S 2p region.

PMID- 9912808
TI  - K x-ray emission from solid neon and from neon implanted into metals.

PMID- 9912809
TI  - Bosonic-degeneracy-induced quantum correlation in a nonlinear atomic beam
      splitter.

PMID- 9912810
TI  - Nondestructive detection of atoms bouncing on an evanescent wave.

PMID- 9912811
TI  - Laser cooling to a single quantum state in a trap: One-dimensional results.

PMID- 9912812
TI  - Programmable cesium Rydberg wave packets.

PMID- 9912813
TI  - Solution of quantum master equations in terms of a non-Hermitian Hamiltonian.

PMID- 9912814
TI  - Cooling of atoms in external fields.

PMID- 9912816
TI  - Phase of the atomic polarization in high-order harmonic generation.

PMID- 9912815
TI  - Numerical modeling of evanescent-wave atom optics.

PMID- 9912817
TI  - Measuring the vibrational energy of a trapped ion.

PMID- 9912818
TI  - Effect of scattered radiation on sub-Doppler cooling.

PMID- 9912819
TI  - Change from an inversion laser to a noninversion laser due to a phase-fluctuation
      effect.

PMID- 9912820
TI  - Quantum-mechanical interference effects in the spontaneous-emission spectrum of a
      driven atom.

PMID- 9912822
TI  - Measurement and preparation using two probe modes.

PMID- 9912821
TI  - Quantum interference in the spectrum of a driven atom: Effects of pumping and
      phase fluctuations.

PMID- 9912823
TI  - Electromagnetic field quantization in absorbing dielectrics.

PMID- 9912824
TI  - Noise in dead zones.

PMID- 9912826
TI  - Hamiltonian theory of symmetric optical network transforms.

PMID- 9912825
TI  - Conditions for anomalous resonance fluorescence in a squeezed vacuum.

PMID- 9912827
TI  - Two-dimensional beam characteristics of triple-pulse pumping a Ne-like Ge soft-x
      ray laser at 19.6 nm.

PMID- 9912828
TI  - Ultrafast modulation spectroscopy in a cascade three-level system.

PMID- 9912829
TI  - Quantum fluctuations of optical solitons in fibers.

PMID- 9912830
TI  - Nearly degenerate four-wave mixing with bichromatic laser fields in a Rb atomic
      system.

PMID- 9912831
TI  - Quantum spatial correlations in the optical parametric oscillator with spherical
      mirrors.

PMID- 9912832
TI  - Tomographic reconstruction of the density matrix via pattern functions.

PMID- 9912834
TI  - Free-induction decay after a pulse saturation for systems with random telegraph
      frequency.

PMID- 9912833
TI  - Transverse modes above and below threshold in a single-frequency laser.

PMID- 9912835
TI  - Noiseless amplification of optical images.

PMID- 9912836
TI  - Abnormal velocity of soliton-type pulses in a nonlinear three-level medium with
      population inversion.

PMID- 9912837
TI  - Polarization dynamics of a J=1/2 J=1/2 anisotropic laser.

PMID- 9912838
TI  - Incompatibility between quantum mechanics and classical realism in the "strong"
      macroscopic limit.

PMID- 9912839
TI  - Atomic anapole moments in the electroweak theory.

PMID- 9912840
TI  - Lyman- alpha doublet intensity ratios for Ti

PMID- 9912841
TI  - Coulomb potential from a particle in uniform ultrarelativistic motion.

PMID- 9912843
TI  - Stabilization and the zero-range models.

PMID- 9912842
TI  - Distortion effects in electron excitation of hydrogen atoms by impact of heavy
      ions.

PMID- 9912844
TI  - Implicit resummation of the perturbation series for multiphoton ionization using
      an effective Hamiltonian.

PMID- 9912846
TI  - Two-mode heterodyne phase detection.

PMID- 9912845
TI  - Causality, memory erasing, and delayed-choice experiments.

PMID- 9912847
TI  - Excitation energies from density-functional orbital energies.

PMID- 9912848
TI  - Theoretical lithium 2 2S-->2 2P and 2 2P-->3 2D oscillator strengths.

PMID- 9912849
TI  - Absolute cross sections for dissociative recombination of HD+: Comparison of
      experiment and theory.

PMID- 9912850
TI  - Quantum statistical effect on ionizing collisions of ultracold metastable Kr
      isotopes.

PMID- 9912851
TI  - Carbon geometry of C3H3+ and C3H4+ molecular ions probed by laser-induced Coulomb
      explosion.

PMID- 9912852
TI  - Direct two-color photoassociative ionization in a rubidium magneto-optic trap.

PMID- 9912853
TI  - Spectral and temporal structure in high harmonic emission from ionizing atomic
      gases.

PMID- 9912854
TI  - Simultaneous trapping of two different atomic species in a vapor-cell magneto
      optical trap.

PMID- 9912855
TI  - Quantum fluctuations in the optical parametric oscillator in the limit of a fast
      decaying subharmonic mode.

PMID- 9912856
TI  - Cavity enhancement of resonant frequencies in semiconductor lasers subject to
      optical injection.

PMID- 9912857
TI  - Light-induced gain and directional energy flow with counterpropagating light
      beams in dense media.

PMID- 9912858
TI  - Circular quantum billiard with a singular magnetic flux line.

PMID- 9912860
TI  - Projection postulate and atomic quantum Zeno effect.

PMID- 9912859
TI  - Entanglement of atomic beams: Tests of complementarity and other applications.

PMID- 9912861
TI  - Unitarity and the time evolution of quantum mechanical states.

PMID- 9912862
TI  - Phase states and phase operators for the quantum harmonic oscillator.

PMID- 9912863
TI  - Hyperfine-structure measurements in Xe

PMID- 9912865
TI  - High-resolution ultraviolet spectra of sympathetically-laser-cooled Cd+ ions.

PMID- 9912864
TI  - Microwave spectroscopy of high-L Rydberg states of neon.

PMID- 9912866
TI  - Observation of interference fringes in Autler-Townes line shapes.

PMID- 9912868
TI  - Pseudoconfigurational approach in relativistic many-body perturbation-theory
      calculations.

PMID- 9912867
TI  - Negative-pion capture process and its chemical effects in some hydrocarbons.

PMID- 9912869
TI  - Regular perturbation theory of relativistic corrections: Basic aspects.

PMID- 9912870
TI  - Hydrogen molecules in a superstrong magnetic field: Excitation levels.

PMID- 9912871
TI  - Minimax variational approach to the relativistic two-electron problem.

PMID- 9912872
TI  - Core-induced chaos in diamagnetic lithium.

PMID- 9912873
TI  - Core-valence and core-core correlation effects on hyperfine-structure parameters
      and oscillator strengths in Tl

PMID- 9912875
TI  - H0+N2 collisions at low-kilo-electron-volt energies.

PMID- 9912874
TI  - High-frequency wings of rototranslational Raman spectra of gaseous nitrogen.

PMID- 9912876
TI  - Charge transfer of 0.5-, 1.5-, and 5-keV protons with atomic oxygen: Absolute
      differential and integral cross sections.

PMID- 9912877
TI  - Approximate charge and transition energy cross-section scaling for excitation of
      atoms colliding with multicharged ions.

PMID- 9912878
TI  - Coulomb three-body effects in low-energy impact ionization of H(1s).

PMID- 9912879
TI  - Quantum suppression of cold atom collisions.

PMID- 9912881
TI  - Total cross sections for electron scattering by CO2 molecules in the energy range
      400-5000 eV.

PMID- 9912880
TI  - High-resolution study of electron capture by 72- and 52-MeV 3He projectiles from
      targets of high atomic number.

PMID- 9912882
TI  - Faddeev calculations of muonic-atom collisions: Scattering and fusion in flight.

PMID- 9912883
TI  - Propagation effects in two-color coherent-control processes.

PMID- 9912884
TI  - Absolute measurement of dielectronic recombination for C3+ in a known external
      field.

PMID- 9912885
TI  - Electron correlation in the decay of resonantly excited 3d3/2,5/2-15p states of
      krypton.

PMID- 9912886
TI  - Energy and angular distributions of electrons from ion impact on atomic and
      molecular hydrogen. III. 28-114-keV He++H2.

PMID- 9912887
TI  - Energy and angular distributions of electrons from ion impact on atomic and
      molecular hydrogen. IV. 28-114-keV He+ + H collisions.

PMID- 9912888
TI  - State independence in atom interferometry and insensitivity to acceleration and
      rotation.

PMID- 9912890
TI  - Quantum field theory of atoms interacting with photons. III. Scattering of weak
      cw light from cold samples of bosonic atoms.

PMID- 9912889
TI  - Matter waves at a vibrating surface: Transition from quantum-mechanical to
      classical behavior.

PMID- 9912891
TI  - Ab initio investigations on Sb4 analogous Zintl clusters.

PMID- 9912892
TI  - Multiphoton absorption and anharmonicity.

PMID- 9912893
TI  - Adiabatic transfer for atomic interferometry.

PMID- 9912895
TI  - Atom-field interactions: Density-matrix equations including quantization of the
      center-of-mass motion.

PMID- 9912894
TI  - Kinetic theory of the evaporative cooling of a trapped gas.

PMID- 9912896
TI  - Transition to space-time chaos in a nonlinear optical system with two-dimensional
      feedback.

PMID- 9912898
TI  - Mirrorless optical bistability of linear molecular aggregates.

PMID- 9912897
TI  - Electromagnetically-induced focusing.

PMID- 9912900
TI  - Optical Larmor clock: Measurement of the photonic tunneling time.

PMID- 9912899
TI  - Nonclassical effects in resonance fluorescence from optical molasses.

PMID- 9912901
TI  - Nonlinear-time-series analysis of chaotic laser dynamics.

PMID- 9912903
TI  - Ramsey spectroscopy with nonclassical light sources.

PMID- 9912902
TI  - Quantum noise of the fundamental soliton.

PMID- 9912904
TI  - Molecular Raman effect in the optical microcavity: QED vacuum confinement of an
      inelastic quantum scattering process.

PMID- 9912905
TI  - Competition and bistability of longitudinal modes in a Raman laser.

PMID- 9912906
TI  - Quantum coherence generated by quantum interference.

PMID- 9912907
TI  - Probability distributions for the phase difference.

PMID- 9912908
TI  - Quasiprobabilities and the nonclassicality of fields.

PMID- 9912909
TI  - Nondegenerate parametric interactions and nonclassical effects.

PMID- 9912910
TI  - Spatiotemporal dynamics of a thin-layer laser.

PMID- 9912911
TI  - Ideal and destructive state reductions of correlated light fields and the
      continuous measurement of photon number.

PMID- 9912912
TI  - Role of electromagnetically induced transparency in resonant four-wave-mixing
      schemes.

PMID- 9912913
TI  - Quantum phase properties of the field in a lossless micromaser cavity.

PMID- 9912914
TI  - Stimulated Raman scattering by a pointlike medium: Classical and quantum
      treatments.

PMID- 9912915
TI  - Superluminal delays of coherent pulses in nondissipative media: A universal
      mechanism.

PMID- 9912916
TI  - Multiconical emission at light counterpropagation in a resonant medium.

PMID- 9912917
TI  - Electron density of closed atomic shells.

PMID- 9912918
TI  - Topological effects associated with fractional statistics in one-dimensional
      mesoscopic rings.

PMID- 9912919
TI  - Stark shift measurement of the (4s)2 1S0-->(4s4p) 3P1 calcium transition.

PMID- 9912920
TI  - Suppression of laser-induced collisional autoionization through
      electromagnetically induced transparency.

PMID- 9912922
TI  - New highly charged fullerene ions: Production and fragmentation by slow ion
      impact.

PMID- 9912921
TI  - Time reversal and parity symmetry breakings of mean fields by propagation.

PMID- 9912923
TI  - Off-shell and on-shell low-frequency approximations for potential scattering in a
      strong elliptically polarized laser field.

PMID- 9912924
TI  - Direct momentum-space calculations for the resonant multiphoton processes of a
      hydrogen atom under intense laser pulses.

PMID- 9912925
TI  - Evolution of coherent hard-x-ray radiation generated in crystalline solids by
      high-intensity femtosecond laser pulses.

PMID- 9912926
TI  - Erratum: Optimal control of strongly driven quantum systems: Fully variational
      formulation and nonlinear eigenfields

PMID- 9912927
TI  - Ballistic expansion of trapped thermal atoms.

PMID- 9912928
TI  - Scaling and virial theorems in current-density-functional theory.

PMID- 9912929
TI  - Circular dichroism in the polarization of the fluorescence resulting from the
      decay of photoionized Ca atoms.

PMID- 9912930
TI  - Ionization steps and phase-space metamorphoses in the pulsed microwave ionization
      of highly excited hydrogen atoms.

PMID- 9912932
TI  - Collisional two- and three-body decay rates of dilute quantum gases at ultralow
      temperatures.

PMID- 9912931
TI  - Orbital effect in elastic electron scattering by a polarized excited target.

PMID- 9912933
TI  - Plasma fluctuations and x-ray laser transverse coherence.

PMID- 9912934
TI  - Steep dispersion and group velocity below c/3000 in coherent population trapping.

PMID- 9912935
TI  - High-order harmonics of 248.6-nm KrF laser from helium and neon ions.

PMID- 9912936
TI  - Resonant photon exchange by atom pairs in high-Q cavities.

PMID- 9912937
TI  - Emergence of classicality via decoherence described by Lindblad operators.

PMID- 9912938
TI  - Uniform regularized semiclassical propagator for the x-2 potential.

PMID- 9912939
TI  - Single-particle density of states, bound states, phase-shift flip, and a
      resonance in the presence of an Aharonov-Bohm potential.

PMID- 9912940
TI  - Embedding of velocity-power forces into a class of energy-dependent potentials
      and their quantization.

PMID- 9912941
TI  - Temperature changes and squeezing properties of the system of time-dependent
      harmonic oscillators.

PMID- 9912942
TI  - Electron temperature and density dependence of E1 and E2 lines in the spectra of
      cobaltlike to potassiumlike ions.

PMID- 9912943
TI  - High-resolution measurements of the K-MM radiative Auger effect in medium-mass
      atoms.

PMID- 9912945
TI  - Chaos in a quasiclassical hadronic atom.

PMID- 9912944
TI  - Muonic three-body Coulomb systems in the hyperspherical approach.

PMID- 9912946
TI  - Nonhydrogenic Rydberg atoms in a magnetic field: A rigorous semiclassical
      approach.

PMID- 9912947
TI  - 3p-photoionization resonances of atomic Fe, Co, and Ni studied by the observation
      of singly and doubly charged photoions.

PMID- 9912948
TI  - Ab initio potential-energy surfaces and electron-spin-exchange cross sections for
      H-O2 interactions.

PMID- 9912950
TI  - Energy-dependent rotational polarization in elementary rearrangement collisions.

PMID- 9912949
TI  - Radiationless resonant Raman scattering interpretation of argon photoion yields
      measured in coincidence with K-LL Auger decay.

PMID- 9912952
TI  - Evidence for multielectron resonances at the Sr K edge.

PMID- 9912951
TI  - Bound-state methods for low-energy electron-ion scattering.

PMID- 9912953
TI  - Electron excitation of optically-allowed transitions in CO2, SF6, CO, F2, and
      SO2.

PMID- 9912954
TI  - Galilean invariance of the Schrodinger equation in the adiabatic approximation:
      The central-field method.

PMID- 9912955
TI  - Multilevel effects on the balance of dipole-allowed to dipole-forbidden
      transitions in Rydberg atoms induced by a dipole interaction with slow charged
      projectiles.

PMID- 9912956
TI  - Inversion of total and differential cross-section data for electron-methane
      scattering.

PMID- 9912957
TI  - Photodetachment of Li- from the Li 3s threshold to the Li 6s threshold.

PMID- 9912958
TI  - Electron degradation and thermalization in H2 gas.

PMID- 9912960
TI  - Slow collisions between highly charged ions and C60: Absolute Delta E values and
      cross sections.

PMID- 9912959
TI  - Continuum absorption spectra in the far wings of the Hg 1S0-->3P1 resonance line
      broadened by Ar.

PMID- 9912961
TI  - Image acceleration of highly charged ions by metal surfaces.

PMID- 9912962
TI  - Spectra of secondary electrons induced by channeled and nonchanneled ions in Si
      and Al.

PMID- 9912963
TI  - Binary-electron emission in grazing ion-surface collisions.

PMID- 9912964
TI  - Measurement and characterization of the three-dimensional coherence function in
      neutron interferometry.

PMID- 9912965
TI  - Ground state of a weakly interacting Bose gas of atoms in a tight trap.

PMID- 9912966
TI  - Decay of trapped ultracold alkali atoms by recombination.

PMID- 9912968
TI  - Nonperturbative analysis of four-wave mixing in a four-level system with three
      strong fields.

PMID- 9912967
TI  - Spin relaxation of optically pumped potassium in an argon buffer gas.

PMID- 9912969
TI  - Keplerian squeezed states and Rydberg wave packets.

PMID- 9912971
TI  - Collective laser cooling of two trapped ions.

PMID- 9912970
TI  - High-velocity dark states in velocity-selective coherent population trapping.

PMID- 9912972
TI  - Composite level approach to the hyperfine structure of the sodium D1 transition.

PMID- 9912973
TI  - Theory of a coherent atomic-beam generator.

PMID- 9912974
TI  - Observation of interference in transitions due to local geometric phases.

PMID- 9912976
TI  - Autler-Townes effect for an atom in a 100% amplitude-modulated laser field. II.
      Experimental results.

PMID- 9912975
TI  - Autler-Townes effect for an atom in a 100% amplitude-modulated laser field. I. A
      dressed-atom approach.

PMID- 9912977
TI  - "Freely" falling two-level atom in a running laser wave.

PMID- 9912979
TI  - Preservation of nonclassical character during the amplification of a Schrodinger
      cat state.

PMID- 9912978
TI  - Coherent population trapping and electromagnetically induced transparency in
      multi-Zeeman-sublevel atoms.

PMID- 9912980
TI  - Zero-point noise in a nonstationary dielectric cavity.

PMID- 9912981
TI  - Spontaneous-emission coupling from multiemitters to the quasimode of a Fabry
      Perot microcavity.

PMID- 9912983
TI  - Stochastic simulations of the quantum Zeno effect.

PMID- 9912982
TI  - Nonlinear optical response of cold atoms.

PMID- 9912984
TI  - Role of inhomogeneous broadening in lasing without inversion in ladder systems.

PMID- 9912985
TI  - Inversionless lasing and photon statistics in a V-type atomic system.

PMID- 9912986
TI  - Quasipatterns in a polarization instability.

PMID- 9912988
TI  - Amplitude-squeezed quantum states produced by the evolution of a quadrature
      squeezed coherent state in a Kerr medium.

PMID- 9912987
TI  - Four-wave mixing in a Bloch two-level system with incoherent laser light having a
      Lorentzian spectral density: Analytic solution and a diagrammatic approach.

PMID- 9912989
TI  - Floquet-state perturbation theory for the radio-frequency modulation of the
      Mossbauer resonance.

PMID- 9912990
TI  - Quantum-limited linewidth of a bad-cavity laser with inhomogeneous broadening.

PMID- 9912991
TI  - Cavity quantum electrodynamics inside a hollow spherical cavity.

PMID- 9912993
TI  - Local-field effects in a dense collection of two-level atoms embedded in a
      dielectric medium: Intrinsic optical bistability enhancement and local
      cooperative effects.

PMID- 9912992
TI  - Selective reflection from a dense atomic vapor.

PMID- 9912994
TI  - Dynamic noise reduction in multilevel lasers: Nonlinear theory and the pump
      operator approach.

PMID- 9912995
TI  - Observation of transparency and population trapping due to atomic coherent
      effects.

PMID- 9912997
TI  - Complementarity and quantum erasure with dispersive atom-field interactions.

PMID- 9912996
TI  - Conditional resonance-fluorescence spectra of single atoms.

PMID- 9912999
TI  - Kinetic-energy release in the dissociative capture-ionization of CO molecules by
      97-MeV Ar14+ ions.

PMID- 9912998
TI  - Multiperturber effects in the Faraday spectrum of Rb atoms immersed in a high
      density Xe gas.

PMID- 9913000
TI  - Quasicausal expansion of the quantum Liouville propagator.

PMID- 9913001
TI  - Effect of quantum interference on multiphoton resonant excitation involving high
      lying Rydberg orbitals.

PMID- 9913002
TI  - Determination of field correlation functions from measured quadrature component
      distributions.

PMID- 9913004
TI  - Resonance states in Li- and B-

PMID- 9913003
TI  - Erratum: Quantum theory of the stability region of an ion in a Paul trap

PMID- 9913005
TI  - Soft-x-ray generation by multiphoton scattering of a laser beam from fast free
      electrons.

PMID- 9913006
TI  - Quantum-classical hybrid approach to helium double photoionization.

PMID- 9913007
TI  - Dissociative recombination of cold OH+: Evidence for indirect recombination
      through excited core Rydberg states.

PMID- 9913008
TI  - Evanescent-wave guiding of atoms in hollow optical fibers.

PMID- 9913009
TI  - Demonstration of x-ray lasing in nickel-like tin.

PMID- 9913010
TI  - Interaction-free preparation.

PMID- 9913011
TI  - Proposed test of Bell's inequality without a detection loophole by using
      entangled Rydberg atoms.

PMID- 9913012
TI  - Loss-error compensation in quantum-state measurements and the solution of the
      time-reversed damping equation.

PMID- 9913013
TI  - Non-Hermitian quantum canonical variables and the generalized ladder operators.

PMID- 9913014
TI  - Nonlinear wave-packet dynamics for a generic one-dimensional time-independent
      system and its application to the hydrogen atom in a weak magnetic field.

PMID- 9913015
TI  - Applications of the Jaynes-Cummings model for the detection of nonorthogonal
      quantum states.

PMID- 9913016
TI  - Study of quantum anharmonic oscillators by state-dependent diagonalization.

PMID- 9913017
TI  - Semiclassical integrable matrix elements.

PMID- 9913018
TI  - Mesoscopic quantum coherences in cavity QED: Preparation and decoherence
      monitoring schemes.

PMID- 9913019
TI  - Nonlinear Schrodinger equation and two-level atoms.

PMID- 9913020
TI  - Determination of frequency-dependent polarizabilities using current density
      functional theory.

PMID- 9913022
TI  - Perturbed energies and eigenfunctions of the curved- and flat-space isotropic
      oscillator via the Riccati equation.

PMID- 9913021
TI  - Photoassociation and bound-bound excitation into the 2 2 Pi state of LiZn, LiCd,
      and NaZn molecules.

PMID- 9913023
TI  - Polarization anisotropy in resonant x-ray emission from molecules.

PMID- 9913025
TI  - Generalized gradient approximation for the relativistic exchange-only energy
      functional.

PMID- 9913026
TI  - Relativistic configuration-interaction calculation of the polarizabilities of
      heliumlike ions.

PMID- 9913024
TI  - Precision measurements on lithium atoms in an electric field compared with R
      matrix and other Stark theories.

PMID- 9913027
TI  - Theory of Auger spectra for molecular-field-split core levels.

PMID- 9913028
TI  - Time-dependent approach to slow ion-atom collisions for systems with one active
      electron.

PMID- 9913029
TI  - Elastic e-NO collisions.

PMID- 9913030
TI  - Energy distributions of emitted ion fragments following C(1s) excitations in CO.

PMID- 9913031
TI  - High-resolution measurement of the dielectronic recombination of fluorinelike
      selenium ions.

PMID- 9913032
TI  - High-resolution study of 1Po double-excitation states in helium.

PMID- 9913033
TI  - Retardation long-range potentials between two helium atoms.

PMID- 9913034
TI  - Inelastic decay processes in a gas of spin-polarized triplet helium.

PMID- 9913036
TI  - Orientation dependence of the differential cross section in elastic electron
      scattering from CH3I molecules.

PMID- 9913035
TI  - Autoionization and interchannel mixing in atomic fluorine: The 2p4(1S)ns,md
      Rydberg series.

PMID- 9913037
TI  - Interpretation of data in multidimensional spaces and its application to Coulomb
      explosion imaging.

PMID- 9913039
TI  - Cross sections of symmetric charge transfer between Gd* and Gd+ in the energy
      range 30-1000 eV.

PMID- 9913038
TI  - Electron-impact excitation of low-lying preionization-edge electronic and Rydberg
      transitions of fluoroform and chloroform: Bethe surfaces and absolute generalized
      oscillator strengths.

PMID- 9913040
TI  - Retardation effects in nonrelativistic two-photon electron bremsstrahlung in the
      Coulomb field.

PMID- 9913041
TI  - Convergence of a lattice calculation for bound-free muon-pair production in
      peripheral relativistic heavy-ion collisions.

PMID- 9913042
TI  - Cross sections of electron excitation out of metastable helium levels with a fast
      metastable target produced via charge exchange.

PMID- 9913043
TI  - Electric-hexadecapole (2(4)-pole) Coulomb integrals.

PMID- 9913044
TI  - Time-dependent close-coupling method for electron-impact ionization of hydrogen.

PMID- 9913045
TI  - K-shell ionization of B, O, and F by 0.4-2.0-MeV He+ ions.

PMID- 9913047
TI  - Ab initio calculation for low-energy elastic scattering of electrons from
      chlorine atoms.

PMID- 9913046
TI  - Photoionization cross sections and oscillator strengths for Fe

PMID- 9913049
TI  - Dispersion interactions between atoms involving electric quadrupole
      polarizabilities.

PMID- 9913048
TI  - Near-threshold study of the polarization of He resonance radiation using an
      energy-selected electron beam.

PMID- 9913050
TI  - Measurement of inelastic electron impact on ozone: Absolute differential cross
      sections for excitation of the Hartley band.

PMID- 9913051
TI  - Absolute differential cross sections for the scattering of kilo-electron-volt O
      atoms.

PMID- 9913052
TI  - Measurement of atomic-hydrogen spin-exchange parameters at 0.5 K using a
      cryogenic hydrogen maser.

PMID- 9913053
TI  - Numerical treatment of the time-dependent Dirac equation in momentum space for
      atomic processes in relativistic heavy-ion collisions.

PMID- 9913055
TI  - Energy- and angle-differential yields of electron emission from thin carbon foils
      after fast proton impact.

PMID- 9913054
TI  - Optical electron polarimetry with heavy noble gases.

PMID- 9913057
TI  - Direct determination of impact-parameter-dependent stopping powers for million
      electron-volt He ions penetrating Er-doped GaAs.

PMID- 9913056
TI  - Energy loss of slow protons channeled in Au.

PMID- 9913058
TI  - Waveguide for cold atoms: Spin-1 magnetic particles and a filamentary current.

PMID- 9913059
TI  - Observation of strongly subhomogeneous linewidths using high-contrast
      transmission spectroscopy: Experiment and theory.

PMID- 9913060
TI  - Ultracold collisions and optical shielding in metastable xenon.

PMID- 9913061
TI  - Dynamics of coherent population trapping states in dense systems.

PMID- 9913062
TI  - Mechanical potentials due to Raman transitions.

PMID- 9913063
TI  - High-density trapping of cesium atoms in a dark magneto-optical trap.

PMID- 9913064
TI  - Trojan wave packets: Mathieu theory and generation from circular states.

PMID- 9913066
TI  - High-harmonic generation in a driven triangular well: The implications of chaos.

PMID- 9913065
TI  - Theory of high-order harmonic generation by an elliptically polarized laser
      field.

PMID- 9913068
TI  - Coulomb effects in multiphoton above-threshold ionization.

PMID- 9913067
TI  - Selective photoionization of the ytterbium atom by coherent two-photon
      excitation.

PMID- 9913069
TI  - Interaction of half-cycle radiation pulse with polarized states of atomic
      hydrogen.

PMID- 9913070
TI  - Sub-Doppler light amplification in a coherently pumped atomic system.

PMID- 9913071
TI  - Self-focused light propagation in a fully saturable medium: Experiment.

PMID- 9913073
TI  - SU(1,1) coherent states defined via a minimum-uncertainty product and an equality
      of quadrature variances.

PMID- 9913072
TI  - Generating mutual coherence from incoherence with the help of a phase-conjugate
      mirror.

PMID- 9913074
TI  - Generalization of damping theory for cavities with mirrors of finite
      transmittivity.

PMID- 9913075
TI  - Asymmetrically pumped nondegenerate second-harmonic generation inside a cavity.

PMID- 9913076
TI  - Controlling optical bistability using electromagnetic-field-induced transparency
      and quantum interferences.

PMID- 9913078
TI  - Experimental observation of parametric effects near period doubling in a loss
      modulated CO2 laser.

PMID- 9913077
TI  - Green-function approach to the radiation-field quantization for homogeneous and
      inhomogeneous Kramers-Kronig dielectrics.

PMID- 9913079
TI  - Two-time intensity correlation in a driven three-level system.

PMID- 9913080
TI  - Gain and coherence effects induced by strong cw-laser coupling in potassium-rare
      gas mixtures.

PMID- 9913081
TI  - Competition between spontaneous scattering and stimulated scattering in an
      injection-seeded Raman amplifier.

PMID- 9913082
TI  - Internal dynamics of multilevel atoms near a vacuum-dielectric interface.

PMID- 9913083
TI  - Optimal control of pulse amplification without inversion.

PMID- 9913084
TI  - SU(2) coherent states in parametric down-conversion.

PMID- 9913086
TI  - Quantum teleportation without irreversible detection.

PMID- 9913085
TI  - Application of associative ionization to the observation of quantum beats in low
      lying atomic resonances.

PMID- 9913087
TI  - Efficient, direct self-consistent-field method in density-functional theory.

PMID- 9913088
TI  - Stochastic variational method with a correlated Gaussian basis.

PMID- 9913090
TI  - Elastic scattering of electrons from singly ionized argon.

PMID- 9913089
TI  - Designations of ds2p energy levels in neutral zirconium, hafnium, and
      rutherfordium (Z=104).

PMID- 9913091
TI  - Spectroscopy of atoms confined to the single node of a standing wave in a
      parallel-plate cavity.

PMID- 9913092
TI  - Dirac's contour representation in thermofield dynamics.

PMID- 9913093
TI  - Interferometric Bell-state analysis.

PMID- 9913094
TI  - Cross section for Compton scattering by polarized bound electrons.

PMID- 9913095
TI  - Photoassociative spectroscopy of ultracold 39K atoms in a high-density vapor-cell
      magneto-optical trap.

PMID- 9913096
TI  - Role of off-resonant excitation in cold collisions in a strong laser field.

PMID- 9913097
TI  - Laser cooling of Rydberg atoms in bichromatic standing waves.

PMID- 9913098
TI  - Minimum-uncertainty angular wave packets and quantized mean values.

PMID- 9913099
TI  - Continuous Stern-Gerlach effect and the quantum-state diffusion model of state
      reduction.

PMID- 9913100
TI  - Higher-order multipole expansion in the Dirac equation.

PMID- 9913101
TI  - Testing quantum mechanics using third-order correlations.

PMID- 9913102
TI  - Method for calculating analytical solutions of the Schrodinger equation:
      Anharmonic oscillators and generalized Morse oscillators.

PMID- 9913103
TI  - Approximate and exact consistency of histories.

PMID- 9913104
TI  - Short-time behavior of the correlation functions for the quantum Langevin
      equation.

PMID- 9913105
TI  - Quantum-state disturbance versus information gain: Uncertainty relations for
      quantum information.

PMID- 9913106
TI  - Concentrating partial entanglement by local operations.

PMID- 9913107
TI  - Cyclic quantum-evolution dependence on the Hamiltonian and geometric phase.

PMID- 9913109
TI  - Nonlocality, Lorentz invariance, and Bohmian quantum theory.

PMID- 9913108
TI  - Exponential divergence of neighboring quantal trajectories.

PMID- 9913110
TI  - QED in optically active media: Enhanced spontaneous emission and chiral, yet
      parity-conserving, corrections to the electron mass.

PMID- 9913111
TI  - How to determine a quantum state by measurements: The Pauli problem for a
      particle with arbitrary potential.

PMID- 9913112
TI  - Landscape of uncertainty in Hilbert space for one-particle states.

PMID- 9913114
TI  - Theory of the Lamb shift in muonic hydrogen.

PMID- 9913113
TI  - Scattering of relativistic pi + pi - atoms by thin magnetic layers for the
      determination of the 2s,2p energy difference.

PMID- 9913115
TI  - Virial expansion of a quantum particle in a classical gas: Application to the
      orthopositronium decay rate.

PMID- 9913116
TI  - Isotope effects on delayed annihilation time spectra of antiprotonic helium atoms
      in a low-temperature gas.

PMID- 9913117
TI  - Ab initio block-Lanczos calculation of the Auger spectra of SiF4: Strong two-hole
      localization effects and foreign imaging.

PMID- 9913118
TI  - Measurement of the lifetime of the 1s2p 3Po state in Be

PMID- 9913119
TI  - Hydrogen atom in very strong magnetic and electric fields.

PMID- 9913120
TI  - Algebraic propagator approaches and intermediate-state representations. I. The
      biorthogonal and unitary coupled-cluster methods.

PMID- 9913121
TI  - Algebraic propagator approaches and intermediate-state representations. II. The
      equation-of-motion methods for N, N+/-1, and N+/-2 electrons.

PMID- 9913123
TI  - Boson-realization model for the vibrational spectra of tetrahedral molecules.

PMID- 9913122
TI  - Spatial effects of radiation trapping in an optically thick atomic vapor excited
      by a laser beam.

PMID- 9913125
TI  - High 2Po resonances of a triply excited lithium atom.

PMID- 9913124
TI  - Large-scale multiconfiguration Dirac-Fock calculations of the hyperfine-structure
      constants of the 2s 2S1/2, 2p 2P1/2, and 2p 2P3/2 states of lithium.

PMID- 9913126
TI  - Time for the empty L shell of a hollow atom to be filled.

PMID- 9913128
TI  - Relativistic configuration-interaction calculations for the 2s-2p3/2 transition
      energies of uranium ions.

PMID- 9913127
TI  - Measurements of the K alpha transition energies of heliumlike krypton.

PMID- 9913129
TI  - Expansions of the correlation-energy density functional Ec

PMID- 9913131
TI  - Stark broadening of resonance transitions in B

PMID- 9913130
TI  - Anomalous Z dependence of a magnetic dipole transition in the Ti

PMID- 9913132
TI  - Theoretical treatment of the bremsstrahlung process in the vicinity of giant
      atomic resonances.

PMID- 9913133
TI  - Electron-impact excitation of the second positive band system (C 3 Pi u-->B 3 Pi
      g) and the C 3 Pi u electronic state of the nitrogen molecule.

PMID- 9913134
TI  - Anisotropic interaction potential between a Rydberg electron and an open-shell
      ion.

PMID- 9913135
TI  - Calculation of cross sections for vibrational excitation and dissociative
      attachment in electron collisions with HBr and DBr.

PMID- 9913136
TI  - 0 degrees binary encounter electron production in 30-MeV Oq++H2, He, O2, Ne, and
      Ar collisions.

PMID- 9913137
TI  - Double-ionization mechanisms and asymmetry parameters for (e,3e-1e) reactions.

PMID- 9913138
TI  - Nonadiabatic coefficients of long-range effective potentials and the Faraday
      effect.

PMID- 9913140
TI  - Line profile of H Lyman- beta emission from dissociative excitation of H2.

PMID- 9913139
TI  - Theory of (e,2e) processes with spin-polarized relativistic electrons.

PMID- 9913141
TI  - L3-subshell alignment in gold and bismuth induced by low-velocity carbon ions.

PMID- 9913142
TI  - Approximate analytical solution of the quantum-mechanical three-body Coulomb
      continuum problem.

PMID- 9913143
TI  - Dielectronic recombination of boronlike argon.

PMID- 9913144
TI  - Energy dependence of cross sections for double-electron capture in 48-132-keV
      C6++He collisions.

PMID- 9913145
TI  - Proton-antiproton impact-electron emission spectra of He: Comparison of theory
      with experiment.

PMID- 9913146
TI  - Validity of the Coulomb-Born approximation for (e,2e) reactions.

PMID- 9913147
TI  - Scaling rule for target ionization by highly charged ions at low-to-intermediate
      velocities.

PMID- 9913149
TI  - Spectroscopic study of electrons emitted in Arq+ (8 <= q <= 16) on Ar at 2.3q keV
      collision energy.

PMID- 9913148
TI  - Electron-impact detachment from negative ions.

PMID- 9913150
TI  - Direct ionization in the quasimolecule H-He.

PMID- 9913151
TI  - Fine-structure effect for (e,2e) collisions.

PMID- 9913153
TI  - Total electron-ion recombination of Fe

PMID- 9913152
TI  - Measurements of recoil and projectile momentum distributions for 19-MeV F9+ + Ne
      collisions.

PMID- 9913154
TI  - Electron-impact excitation cross sections for allowed transitions in atoms.

PMID- 9913155
TI  - Berry connection in scattering processes.

PMID- 9913156
TI  - Approximate triangle amplitude for three-body charge exchange processes.

PMID- 9913157
TI  - Relativistic theory of stopping for heavy ions.

PMID- 9913158
TI  - Energy and lifetime of one-electron multicharged-ion states in front of an Al
      surface.

PMID- 9913159
TI  - Pumping atoms into a Bose-Einstein condensate in the boson-accumulation regime.

PMID- 9913160
TI  - Bosons in anisotropic traps: Ground state and vortices.

PMID- 9913162
TI  - Many-body forces and electron correlation in small metal clusters.

PMID- 9913161
TI  - Geometric phase in coupled neutron interference loops.

PMID- 9913163
TI  - Adiabatic processes in three-level systems.

PMID- 9913165
TI  - Modifications to the chaotic dynamics of laser-cooled atoms due to spontaneous
      emission.

PMID- 9913164
TI  - First iteration within the high-frequency Floquet theory of laser-atom
      interactions.

PMID- 9913167
TI  - Influence of atomic coherence induced by laser-assisted near-resonant collisions
      on the far-wing absorption profile.

PMID- 9913166
TI  - Temperature and magnetism of gray optical lattices.

PMID- 9913169
TI  - Model for studies of laser-induced nonlinear processes in molecules.

PMID- 9913168
TI  - Nuclear excitation by laser-assisted electronic transitions.

PMID- 9913170
TI  - Role of permanent dipoles and orientational averaging in the phase control of two
      color, simultaneous one- and three-photon molecular excitations.

PMID- 9913172
TI  - Multilevel systems: Simultaneously forbidden combination resonances.

PMID- 9913171
TI  - Effects of coherent coupling of autoionizing states on multiphoton ionization.

PMID- 9913173
TI  - Dipole-dipole interaction in three-dimensional optical lattices.

PMID- 9913175
TI  - Theory of fluorescence and probe absorption in the presence of a driving field
      using semiclassical dressed states.

PMID- 9913174
TI  - Scaling laws in velocity-selective coherent-population-trapping laser cooling.

PMID- 9913177
TI  - Two-photon bistable switching of an optically pumped atomic neon Raman laser.

PMID- 9913176
TI  - Non-rotating-wave master equation.

PMID- 9913179
TI  - Quantum state measurement by realistic heterodyne detection.

PMID- 9913178
TI  - rf-dressed dark resonance in a symmetric five-level system.

PMID- 9913180
TI  - Generation and detection of photons in a cavity with a resonantly oscillating
      boundary.

PMID- 9913181
TI  - Dynamical localization of atomic de Broglie waves: The influence of spontaneous
      emission.

PMID- 9913182
TI  - Quantum-state diffusion with a moving basis: Computing quantum-optical spectra.

PMID- 9913183
TI  - Construction of quantum states of the radiation field by discrete coherent-state
      superpositions.

PMID- 9913184
TI  - Vacuum-field Rabi splitting in the presence of inhomogeneous broadening:
      Resolution of a homogeneous linewidth in an inhomogeneously broadened system.

PMID- 9913185
TI  - Quantum description of the input and output electromagnetic fields in a
      polarizable confined system.

PMID- 9913186
TI  - Unpolarized light: Classical and quantum states.

PMID- 9913187
TI  - Simulation of quantum-state endoscopy.

PMID- 9913188
TI  - Lasing without inversion in a -type system: Transient and steady-state analysis.

PMID- 9913189
TI  - High harmonic generation in a static magnetic field.

PMID- 9913190
TI  - Pattern formation in an alkali-metal vapor with a feedback mirror.

PMID- 9913191
TI  - Strongly pulsating lasers with delay.

PMID- 9913192
TI  - Theory of quantum radiation observed as sonoluminescence.

PMID- 9913193
TI  - Doubly forbidden second-harmonic generation from isotropic suspensions: Studies
      on the purple membrane of Halobacterium halobium.

PMID- 9913194
TI  - Nonlinear optical response of layered composite materials.

PMID- 9913195
TI  - Measurement of spontaneous-emission enhancement near the one-dimensional photonic
      band edge of semiconductor heterostructures.

PMID- 9913197
TI  - Dynamics of a Brillouin fiber ring laser: Off-resonant case.

PMID- 9913196
TI  - Two-photon geometric optics.

PMID- 9913198
TI  - An alternative interpretation of the Zeeman and Faraday laser.

PMID- 9913199
TI  - Sub-Doppler resolution in inhomogeneously broadened media using intense control
      fields.

PMID- 9913200
TI  - Anomalous resonance fluorescence from an atom in a cavity with injected squeezed
      vacuum.

PMID- 9913202
TI  - Preparation of multiatom entangled states through dispersive atom-cavity-field
      interactions.

PMID- 9913201
TI  - Five two-bit quantum gates are sufficient to implement the quantum Fredkin gate.

PMID- 9913203
TI  - Measurements of positronium-formation cross sections for positrons scattered by
      Rb atoms.

PMID- 9913204
TI  - Production or annihilation of positrons with bound electrons.

PMID- 9913205
TI  - Projectile dependence of single-excitation cross sections at intermediate
      velocities.

PMID- 9913206
TI  - Influence of the first-order polarization on the stopping power for bare charges
      in the jellium model.

PMID- 9913208
TI  - Effect of continuum-continuum and quasibound-continuum above-threshold
      transitions on (1+1)-photon resonance-enhanced multiphoton autoionization.

PMID- 9913207
TI  - Multiphotonic lattices and Stark localization of electromagnetic fields in one
      dimension.

PMID- 9913210
TI  - Generating-function approach to the moment problem for the density matrix of a
      single mode.

PMID- 9913209
TI  - Transient laser cooling of two-level quantum systems with narrow natural
      linewidths.

PMID- 9913212
TI  - Relationship between field and atomic squeezing in the thermal Jaynes-Cummings
      model.

PMID- 9913211
TI  - Optical pumping with nonclassical light.

PMID- 9913213
TI  - Comment on "Definition and construction of the quantum soliton states in optical
      fibers"

PMID- 9913215
TI  - Erratum: Direct two-color photoassociative ionization in a rubidium magneto-optic
      trap

PMID- 9913214
TI  - Erratum: Auger decay of Na-like Si3+(2p53lnl') states formed in slow Si5+-->He
      and Ar ion-atom collisions

PMID- 9913216
TI  - Local-realism violations in two-particle interferometry.

PMID- 9913217
TI  - Laser-induced resonant transitions in the v=n-l-1=2 and 3 metastable cascades of
      antiprotonic 3He atoms.

PMID- 9913218
TI  - Density behavior of the double rotational transition in liquid parahydrogen.

PMID- 9913219
TI  - Hyperfine structure of the Na2 0g- long-range molecular state.

PMID- 9913220
TI  - Inner-shell excitation in heavy-ion-solid-target collisions.

PMID- 9913221
TI  - Auger resonant Raman spectroscopy used to study the angular distributions of the
      Xe 4d5/2-->6p decay spectrum.

PMID- 9913222
TI  - Properties of a Bose-Einstein condensate in an anisotropic harmonic potential.

PMID- 9913224
TI  - Multiple ionization of atomic and molecular iodine in strong laser fields.

PMID- 9913223
TI  - Expansion of a Bose-Einstein condensate in a harmonic potential.

PMID- 9913225
TI  - Harmonic generation from a coherent superposition of states.

PMID- 9913226
TI  - Motion tomography of a single trapped ion.

PMID- 9913227
TI  - Breaking of symmetry through spontaneous emission.

PMID- 9913228
TI  - Determination of occupation probabilities from time-averaged position
      distributions.

PMID- 9913230
TI  - Solving some two-body dynamical problems in < zeta |-< eta | representation.

PMID- 9913229
TI  - Experimental test of Selleri's variable photodetection-probability model.

PMID- 9913232
TI  - Generalized semiclassical-phase-index formulas via sequential stationary phase.

PMID- 9913231
TI  - Weak-interaction contributions to hyperfine splitting and Lamb shift.

PMID- 9913233
TI  - Small denominators, frequency operators, and Lie transforms for nearly integrable
      quantum spin systems.

PMID- 9913234
TI  - Spontaneous emission from an extended wave packet: Field correlations.

PMID- 9913235
TI  - Realistic lower bounds for the factorization time of large numbers on a quantum
      computer.

PMID- 9913236
TI  - Relativistic oscillator of constant period.

PMID- 9913237
TI  - Discrete Wigner function and quantum-state tomography.

PMID- 9913238
TI  - Resonance ionization spectroscopy and analysis on even-parity states of Pb

PMID- 9913239
TI  - Fine-structure measurements for negative ions: Studies of Se- and Te-

PMID- 9913240
TI  - Renormalization of the second-order electron self-energy for a tightly bound
      atomic electron: A detailed derivation.

PMID- 9913241
TI  - Fine structure in a strong magnetic field: Paschen-Back effect reconsidered in
      Rydberg atoms.

PMID- 9913242
TI  - Transition energies of barium and radium by the relativistic coupled-cluster
      method.

PMID- 9913243
TI  - Neutral "parent" states of the ionic He2- 4 Phi g.

PMID- 9913244
TI  - Measurement of muon transfer from proton to triton and pp micro molecular
      formation in solid hydrogen.

PMID- 9913246
TI  - Anomalies of pressure broadening in the H2 S0(3) transition versus perturber
      concentration.

PMID- 9913245
TI  - Absolute generalized oscillator strengths of 2 1S and 2 1P excitations of helium
      measured by angle-resolved electron-energy-loss spectroscopy.

PMID- 9913247
TI  - Hyperfine structure in photoassociative spectra of 6Li2 and 7Li2.

PMID- 9913248
TI  - Molecular pendular states in intense laser fields.

PMID- 9913249
TI  - Experimental investigation of excited-state lifetimes in atomic ytterbium.

PMID- 9913250
TI  - Resonant excitation channels in the 3d10-3d94s and 3d10-3d94p transitions of
      nickel-like Mo14+ and Zr12+

PMID- 9913252
TI  - Oscillator strengths for N

PMID- 9913251
TI  - Local temperature in an electronic system.

PMID- 9913253
TI  - Effects of impurity atoms and molecules on the lifetime of antiprotonic helium
      atoms.

PMID- 9913254
TI  - Density-functional exchange identity from coordinate scaling.

PMID- 9913255
TI  - Generalized gradient correction for exchange: Deduction from the oscillator
      model.

PMID- 9913256
TI  - (2p2)1S state of beryllium.

PMID- 9913257
TI  - Threshold anomaly in S scattering with Coulomb charge exchange.

PMID- 9913258
TI  - Resonances in e+-He+ scattering.

PMID- 9913259
TI  - Cross section and angular distribution for the photodetachment of He-(1s2s2p 4Po)
      below the He(n=4) threshold.

PMID- 9913260
TI  - Excitation-autoionization cross sections and rate coefficients of Cu-like ions.

PMID- 9913261
TI  - Simulation of excited-state formation of hydrogen in transmission of relativistic
      H- ions through thin foils.

PMID- 9913263
TI  - Trends in 4d-subshell photoabsorption along the iodine isonuclear sequence: I,
      I+, and I2+

PMID- 9913262
TI  - Measurement of H-, H0, and H+ yields produced by foil stripping of 800-MeV H-
      ions.

PMID- 9913265
TI  - Angular distributions of electrons following photoionization of spherically
      symmetric Rydberg states in alkaline-earth atoms.

PMID- 9913264
TI  - Fully relativistic distorted-wave Born procedure for electron-impact excitation.

PMID- 9913266
TI  - Angular asymmetry of low-energy electron emission in ion-atom collisions.

PMID- 9913268
TI  - Near-threshold study of the polarization of rare-gas resonance radiation: Neon.

PMID- 9913267
TI  - Calculation of near-threshold O- photodetachment, including fine-structure
      effects.

PMID- 9913269
TI  - Relativistic-energy-sharing (e,2e) collisions in coplanar constant Theta 1,2
      geometry.

PMID- 9913270
TI  - Features of the Auger resonant Raman effect in experimental spectra.

PMID- 9913271
TI  - Analysis of final-state momentum distributions of ionization products in ion-atom
      collisions.

PMID- 9913273
TI  - Computation of Compton profiles in a weak laser field.

PMID- 9913272
TI  - Partial cross sections for excitation of He(3 1D) states by electron impact.

PMID- 9913274
TI  - Time-dependent quantum dynamics of laser-induced intramolecular energy transfer.

PMID- 9913275
TI  - Low-energy scattering of muonic hydrogen on hydrogen molecules: A semiclassical
      approach.

PMID- 9913276
TI  - Longitudinal recoil-ion momentum distribution in ionization collisions by neutral
      projectiles near the kinematical threshold.

PMID- 9913278
TI  - Angular distribution of decay electrons from the 6p resonance excitations in
      xenon.

PMID- 9913277
TI  - Positronium-alkali-ion scattering in the close-coupling approximation.

PMID- 9913279
TI  - Electron-hydrogen fluoride scattering at ultralow electron energies: Possible
      role of dipole-supported states.

PMID- 9913281
TI  - Atom optics in the time domain.

PMID- 9913280
TI  - Bichromatic atomic lens.

PMID- 9913283
TI  - Collisionless motion and evaporative cooling of atoms in magnetic traps.

PMID- 9913282
TI  - Interaction of intense laser pulses with atomic clusters.

PMID- 9913284
TI  - Anomalous diffusion and Levy walks in optical lattices.

PMID- 9913286
TI  - Transient coherent population trapping in a closed loop interaction scheme.

PMID- 9913285
TI  - Two-electron atoms in superintense radiation fields: Dichotomy and stabilization.

PMID- 9913287
TI  - Band gaps for atoms in light-based waveguides.

PMID- 9913288
TI  - High-order harmonic generation processes in classical and quantum anharmonic
      oscillators.

PMID- 9913289
TI  - Measurements of intensity correlations of scattered light from laser-cooled
      atoms.

PMID- 9913290
TI  - Laser-assisted collisions: The Kroll-Watson formula and bremsstrahlung theory.

PMID- 9913291
TI  - van der Waals dispersion forces in electromagnetic fields.

PMID- 9913292
TI  - Transverse-mode selection in single-longitudinal-mode lasers.

PMID- 9913293
TI  - Nonequilibrium Green-function theory of quantum-optical correlations.

PMID- 9913294
TI  - Polarization stability and dynamics in a model for a polarization-isotropic laser
      that goes beyond third-order Lamb theory.

PMID- 9913296
TI  - Vector effects in self-focusing.

PMID- 9913295
TI  - Theory of the two-photon micromaser: Linewidth.

PMID- 9913297
TI  - Microscopic theory of quantization of radiation in molecular dielectrics: Normal
      mode representation of operators for local and averaged (macroscopic) fields.

PMID- 9913298
TI  - Dynamical structures of a photorefractive oscillator.

PMID- 9913299
TI  - Lowering of threshold conditions for nonlinear effects in a microsphere.

PMID- 9913301
TI  - Intensity dependence of the phase of harmonics in one- and two-frequency laser
      fields.

PMID- 9913300
TI  - Dipole-dipole interaction in squeezed vacua.

PMID- 9913302
TI  - Spontaneous emission in a planar Fabry-Perot microcavity.

PMID- 9913303
TI  - Quantum-field coherence in a Raman amplifier.

PMID- 9913304
TI  - Role of plasma cooling, heating, and memory effects in subpicosecond pulse
      propagation in semiconductor amplifiers.

PMID- 9913305
TI  - Photon antibunching by destructive two-photon interference.

PMID- 9913307
TI  - Interaction of a two-level atom with a squeezed vacuum: Photon statistics and
      spectra.

PMID- 9913306
TI  - Statistical-noise properties of an optical amplifier utilizing two-beam coupling
      in atomic-potassium vapor.

PMID- 9913308
TI  - Soft-x-ray lasing at 32.6 nm in Ne-like Ti ions driven by 40 J of energy from two
      650-ps laser pulses.

PMID- 9913310
TI  - Total atomic energies using indirect-path methods.

PMID- 9913309
TI  - Saturation effects in three-level selective reflection.

PMID- 9913311
TI  - Pseudopotentials from electron density.

PMID- 9913312
TI  - Transition functional method in the density-functional theory.

PMID- 9913313
TI  - Quadrupole moments and polarizabilities of the first-row stable atomic anions.

PMID- 9913314
TI  - Double-electron-capture processes in B4++He collisions.

PMID- 9913315
TI  - Angular distributions for double photoionization of helium: Discrepancies between
      theory and experiment.

PMID- 9913317
TI  - Resonantly enhanced multiphoton ionization of xenon in Bessel beams.

PMID- 9913316
TI  - Loss of spatial coherence in atomic deflection from an off-resonant quantized
      standing-wave field.

PMID- 9913318
TI  - Kinetics of photon correlation functions under the time-dependent quadratic
      Hamiltonian.

PMID- 9913319
TI  - Decomposition of the electromagnetic field in lossless inhomogeneous dispersive
      dielectrics.

PMID- 9913321
TI  - Squeezing and antisqueezing in homodyne measurements.

PMID- 9913320
TI  - Time-dependent quantum systems and the invariant Hermitian operator.

PMID- 9913322
TI  - Protective measurement of the wave function of a single squeezed harmonic
      oscillator state.

PMID- 9913323
TI  - Improving energies by using exact electron densities.

PMID- 9913324
TI  - Employing homogeneity properties of density functionals to determine the total
      electronic energy.

PMID- 9913325
TI  - Picosecond laser probing of rotational alignment of NO in CO2.

PMID- 9913327
TI  - Ionization of very-high-n Rydberg atoms by half-cycle pulses in the short-pulse
      regime.

PMID- 9913326
TI  - Interaction of slow Ar(17,18)+ ions with C60: An insight into ion-surface
      interactions.

PMID- 9913328
TI  - Recollisions, bremsstrahlung, and attosecond pulses from intense laser fields.

PMID- 9913329
TI  - Spin-orbit coupling in free-space Laguerre-Gaussian light beams.

PMID- 9913330
TI  - Optimal control of piezophotonic and magnetophotonic switching in a dense medium
      of three-level atoms.

PMID- 9913331
TI  - Entropy of phase measurement: Quantum phase via quadrature measurement.

PMID- 9913332
TI  - delta -function spin-1/2 fermions in a one-dimensional potential well.

PMID- 9913333
TI  - Larmor clock for tunneling times.

PMID- 9913334
TI  - Coherent splitting of single photons by an ideal beam splitter.

PMID- 9913335
TI  - Accelerating light clocks.

PMID- 9913337
TI  - Quantum damping of position due to energy measurements.

PMID- 9913336
TI  - Heisenberg-picture approach to the exact quantum motion of a time-dependent
      forced harmonic oscillator.

PMID- 9913339
TI  - Optical quantum nondemolition measurements and the Copenhagen interpretation.

PMID- 9913338
TI  - Jamming nonlocal quantum correlations.

PMID- 9913340
TI  - Special functions and quantum mechanics in phase space: Airy functions.

PMID- 9913341
TI  - Semiclassical wave equation and exactness of the WKB method.

PMID- 9913342
TI  - Geometric and nongeometric effects in an unbounded mechanical system.

PMID- 9913343
TI  - Logical reversibility in quantum measurement: General theory and specific
      examples.

PMID- 9913344
TI  - Generation of four-photon coherent states in dispersive cavity QED.

PMID- 9913345
TI  - Parametrized discrete phase-space functions.

PMID- 9913346
TI  - Exponential and Laguerre squeezed states for su(1,1) algebra and the Calogero
      Sutherland model.

PMID- 9913347
TI  - Theoretical study of the electronic structure of the Sr2 molecule.

PMID- 9913348
TI  - Bound states with arbitrary angular momenta in nonrelativistic three-body
      systems.

PMID- 9913349
TI  - Nuclear quadrupole coupling constants from the Gaussian density-functional
      method.

PMID- 9913350
TI  - Adiabatic potential-energy surfaces of the H2 + ion in a strong magnetic field.

PMID- 9913352
TI  - QED corrections to O( alpha 7mc2) fine-structure splittings in helium.

PMID- 9913351
TI  - Multipole treatment of radiation trapping in a stepwise-excitation, electron
      photon coincidence experiment.

PMID- 9913353
TI  - Prospects for parity-nonconservation experiments with highly charged heavy ions.

PMID- 9913354
TI  - Calculated energy levels of thallium and eka-thallium (element 113).

PMID- 9913355
TI  - Hyperspherical approach to three-electron atomic systems.

PMID- 9913356
TI  - Simple spin correction of unrestricted density-functional calculation.

PMID- 9913357
TI  - X-ray observations of 2l-nl' transitions from Zr, Nb, Mo, and Pd in near-neonlike
      charge states.

PMID- 9913359
TI  - Relativistic many-body perturbation theory for general open-shell multiplet
      states of atoms.

PMID- 9913358
TI  - Exact local exchange potential from Fock equations at vanishing coupling
      constant, and delta Tc/ delta n from wave-function calculations at full coupling
      constant.

PMID- 9913360
TI  - Measurement and interpretation of the polarization of the x-ray line emission of
      heliumlike Fe

PMID- 9913361
TI  - Determination of the ground-state hyperfine splitting of trapped 113Cd+ ions.

PMID- 9913363
TI  - Abnormal branching ratios in laser-excited Rydberg series of Yb+, Ba+, and Sr+

PMID- 9913362
TI  - Electron correlations in multiconfiguration atomic wave functions.

PMID- 9913364
TI  - Search for 1s2s 3S1-1s2p 3P2 decay in U90+

PMID- 9913366
TI  - Fragmentation of atomic systems.

PMID- 9913365
TI  - Influence of an intense magnetic field on transition arrays.

PMID- 9913367
TI  - Large-scale multiconfiguration Hartree-Fock and configuration-interaction
      calculations of the transition probability and hyperfine structures in the sodium
      resonance transition.

PMID- 9913368
TI  - Electron affinity of Pa by 7p attachment and hyperfine structure constants for Pa

PMID- 9913369
TI  - Relativistic many-body calculations of the energies of n=2 states for the
      berylliumlike isoelectronic sequence.

PMID- 9913370
TI  - Pressure-dependent quenching of Rb 5P states in liquid helium.

PMID- 9913371
TI  - Collapse of the Zeeman structure of the hydrogen atom in an external electric
      field.

PMID- 9913372
TI  - Multichannel density-functional calculations for atoms and atomic chains in
      magnetic fields of compact stars.

PMID- 9913374
TI  - Signatures of target e-e correlations in the angular distribution of (e,3e)
      differential cross sections for the ionization of helium by fast electrons.

PMID- 9913373
TI  - Extension of scattering theory for finite times: Three-body scattering.

PMID- 9913375
TI  - Vibrational branching ratios for single-photon ionization of Na2.

PMID- 9913376
TI  - High-resolution C 1s photoelectron spectra of methane.

PMID- 9913377
TI  - Electron affinity of Li: A state-selective measurement.

PMID- 9913378
TI  - Collisional mixing among excited degenerate states in inelastic ion-atom
      collisions.

PMID- 9913380
TI  - Adiabatic inner-shell ionization by light ions.

PMID- 9913379
TI  - Measurements of cross sections and oscillator strengths by electron impact for
      the 5d and 7s levels of Xe.

PMID- 9913382
TI  - Triply differential cross section and polarization correlations in electron
      bremsstrahlung emission.

PMID- 9913381
TI  - Minimum principle for autoionizing states.

PMID- 9913383
TI  - Electron capture in collisions of O2+(3P) ions with He atoms at energies below 10
      keV: The effect of metastable O2+(1D) ions.

PMID- 9913384
TI  - Elastic scattering of excited muonic hydrogen.

PMID- 9913385
TI  - Double electron capture in low-energy Fe17++He collisions.

PMID- 9913386
TI  - Circular-dichroism effects on photoelectron angular distributions for the 7P and
      8P states of cesium.

PMID- 9913387
TI  - Charge-state dependence of K-shell x-ray production in aluminum by 2-12-MeV
      carbon ions.

PMID- 9913388
TI  - Dielectronic processes producing radiative stabilization in slow Ne10++He
      collisions.

PMID- 9913389
TI  - Energy-momentum structure of the krypton valence shell by electron-momentum
      spectroscopy.

PMID- 9913390
TI  - Analytic Born completion in the calculation of electron-molecule differential
      cross sections.

PMID- 9913391
TI  - Auger deexcitation in a helium atom induced by a metal surface.

PMID- 9913392
TI  - Neutralization and equilibration of highly charged argon ions at grazing
      incidence on a graphite surface.

PMID- 9913393
TI  - Atomic de Broglie waves in multiple optical standing waves.

PMID- 9913394
TI  - Ground state and excited states of a confined condensed Bose gas.

PMID- 9913396
TI  - Interference of two condensates.

PMID- 9913395
TI  - Nonequilibrium condensates and lasers without inversion: Exciton-polariton
      lasers.

PMID- 9913397
TI  - Bose-Einstein condensation of atoms in a trap.

PMID- 9913399
TI  - Two-color above-threshold ionization of atoms.

PMID- 9913398
TI  - Multiple reflection of an extended atomic wave packet through a square-profile
      laser beam.

PMID- 9913400
TI  - Fluorescence and absorption by a two-level atom in a bichromatic field with one
      strong and one weak component.

PMID- 9913401
TI  - Landau-Zener model: Effects of finite coupling duration.

PMID- 9913403
TI  - Theory of the Kapitza-Dirac effect in strong radiation fields.

PMID- 9913402
TI  - Generalized analytical description of light-induced drift and an experimental
      test using C2H4.

PMID- 9913404
TI  - Nonresonant multiphoton double ionization of Ga and As probed by a picosecond
      double-pulse technique.

PMID- 9913405
TI  - Theoretical study of the vibrational-branching ratio and photoelectron angular
      distribution in (1+1')-photon resonance-enhanced multiphoton ionization of HD and
      D2 molecules.

PMID- 9913406
TI  - Anomalous light-induced drift of potassium in Ne plus rare-gas mixtures.

PMID- 9913407
TI  - Interferometric characterization of Raman redistribution among perturbed Rydberg
      states of barium.

PMID- 9913408
TI  - Collisions of dressed ground-state atoms.

PMID- 9913409
TI  - Gravito-optical trapping of three-level atoms.

PMID- 9913411
TI  - Mechanism for period-doubling bifurcation in a semiconductor laser subject to
      optical injection.

PMID- 9913410
TI  - Coherence properties of entangled light beams generated by parametric down
      conversion: Theory and experiment.

PMID- 9913412
TI  - High-contrast, high-resolution focusing of neutral atoms using light forces.

PMID- 9913414
TI  - Optical media with an imaginary third-order nonlinearity analyzed by Hamiltonian
      systems.

PMID- 9913413
TI  - One-atom maser: Phase-sensitive measurements.

PMID- 9913415
TI  - Global-stability analysis of transverse modes in laser systems under
      inhomogeneous pumping.

PMID- 9913416
TI  - Collective-resonance fluorescence in an ideal cavity.

PMID- 9913417
TI  - Lang and Kobayashi phase equation.

PMID- 9913418
TI  - Transverse mode competition in a CO2 laser.

PMID- 9913419
TI  - Probe absorption spectra for driven atomic systems in a narrow bandwidth squeezed
      vacuum.

PMID- 9913421
TI  - Pulse splitting of self-focusing beams in normally dispersive media.

PMID- 9913420
TI  - Spontaneous emission in an absorptive and inhomogeneous cavity.

PMID- 9913423
TI  - Traveling-wave states and secondary instabilities in optical parametric
      oscillators.

PMID- 9913422
TI  - Squeezed states and uncertainty relations in rotating frames and Penning traps.

PMID- 9913424
TI  - Dynamics of a two-level model with fine structure.

PMID- 9913426
TI  - Running transverse waves in optical phase conjugation.

PMID- 9913425
TI  - Vibronic mode couplings in adsorbed molecules analyzed by doubly resonant sum
      frequency generation.

PMID- 9913427
TI  - Unbalanced homodyning for quantum state measurements.

PMID- 9913429
TI  - Lasing on the 3d-->3p neonlike x-ray laser transitions driven by a self-photo
      pumping mechanism.

PMID- 9913428
TI  - Optimized preparation of quantum states by conditional measurements.

PMID- 9913431
TI  - Theory of two-photon down-conversion in the presence of mirrors.

PMID- 9913430
TI  - Measurement of Lorentzian linewidths by pulse propagation delay.

PMID- 9913432
TI  - Electromagnetic field quantization in absorbing dielectrics. II.

PMID- 9913433
TI  - Nonlocality of a single photon in cavity QED.

PMID- 9913435
TI  - Preparation of a four-atom Greenberger-Horne-Zeilinger state.

PMID- 9913434
TI  - Factoring integers with Young's N-slit interferometer.

PMID- 9913436
TI  - Isotropic collision-induced scattering from high-temperature gaseous mercury.

PMID- 9913437
TI  - Electronic excitation of H2 by e+ impact using adiabatic nuclear rotation model.

PMID- 9913438
TI  - Comment on "Why quantum dynamics can be formulated as a Markov process"

PMID- 9913440
TI  - Reply to "Comment on 'Phase-invariant clock hypothesis for accelerating systems'
      "

PMID- 9913439
TI  - Comment on "Phase-invariant clock hypothesis for accelerating systems"

PMID- 9913442
TI  - Reply to "Comment on 'Determination of highly excited states of diatomic
      molecular ions using exact H2 +-like orbitals' "

PMID- 9913441
TI  - Comment on "Determination of highly excited states of diatomic-molecular ions
      using exact H2 +-like orbitals"

PMID- 9913444
TI  - Reply to "Comment on 'Intermolecular translational-rotational contribution to
      nuclear-spin relaxation in liquids' "

PMID- 9913443
TI  - Comment on "Intermolecular translational-rotational contribution to nuclear-spin
      relaxation in liquids"

PMID- 9913445
TI  - Erratum: Nuclear-polarization contribution to the Lamb shift in actinide nuclei

PMID- 9913447
TI  - Additional motional-magnetic-field considerations for electric-dipole-moment
      experiments.

PMID- 9913446
TI  - Erratum: Generalized gradient approximation for the relativistic exchange-only
      energy functional

PMID- 9913448
TI  - Compton-scattering contribution to the double ionization of He in the A2
      approximation.

PMID- 9913450
TI  - Direct observation of the double Auger decay of a K hole.

PMID- 9913449
TI  - Singlet s-wave scattering lengths of 6Li and 7Li.

PMID- 9913451
TI  - Compton double-to-single ionization ratio of helium at 57 keV.

PMID- 9913453
TI  - Atom trapping in nondissipative optical lattices.

PMID- 9913452
TI  - Static-electric-field effects on high harmonic generation.

PMID- 9913454
TI  - Polarization dynamics in a vertical-cavity laser with an axial magnetic field.

PMID- 9913456
TI  - Modified WKB approximation.

PMID- 9913455
TI  - Laser cooling of cesium atoms in gray optical molasses down to 1.1 microK.

PMID- 9913457
TI  - Quantum stereographic projection and the homographic oscillator.

PMID- 9913458
TI  - Extension of the Dirac-Bergmann theory of constrained systems.

PMID- 9913459
TI  - Reconstruction of the exact ground-state energy of the quartic anharmonic
      oscillator from the coefficients of its divergent perturbation expansion.

PMID- 9913460
TI  - Relativistic neoclassical radiation theory.

PMID- 9913461
TI  - Angular velocity operator and q-deformation structure.

PMID- 9913462
TI  - Security against eavesdropping in quantum cryptography.

PMID- 9913463
TI  - Anomalous diffusion and environment-induced quantum decoherence.

PMID- 9913464
TI  - Extended Feynman rule and the two-slit experiment.

PMID- 9913465
TI  - Role of core-scattered closed orbits in nonhydrogenic atoms.

PMID- 9913466
TI  - Approximate quantum Fourier transform and decoherence.

PMID- 9913467
TI  - Quantum networks for elementary arithmetic operations.

PMID- 9913468
TI  - Right-unitary transformation theory and applications.

PMID- 9913469
TI  - Bell's inequality, trichotomic observables, and supplementary assumptions.

PMID- 9913470
TI  - Probabilities for histories in nonrelativistic quantum mechanics.

PMID- 9913472
TI  - Hartree-Fock studies of atoms in strong magnetic fields.

PMID- 9913471
TI  - Potential curves for the ground and numerous highly excited electronic states of
      K2 and NaK.

PMID- 9913473
TI  - Electron-impact-induced K plus M shell ionization in solid targets of medium-Z
      elements studied by means of high-resolution x-ray spectroscopy.

PMID- 9913475
TI  - Stationary coupled-cluster approaches to molecular properties: A comparative
      study.

PMID- 9913474
TI  - Model for the optical excitations of molecules: Interactions and electron-pairing
      effects.

PMID- 9913476
TI  - Physical interpretation of information entropy: Numerical evidence of the Collins
      conjecture.

PMID- 9913477
TI  - Explicit formulas for the matrix elements of a symmetrized combination of two
      U(2n) generators in the unitary-group approach.

PMID- 9913478
TI  - Variational calculation of polarizability and second hyperpolarizability of two
      electron systems.

PMID- 9913479
TI  - Exact solution for a hydrogen atom in a magnetic field of arbitrary strength.

PMID- 9913480
TI  - Femtosecond wave-packet propagation in spin-orbit-coupled electronic states of
      39,39K2 and 39,41K2.

PMID- 9913482
TI  - Discrete structure in the 3d photoabsorption spectra of neutral, singly ionized
      and doubly ionized bromine.

PMID- 9913481
TI  - Optical spectroscopy of high-L n=10 Rydberg states of nitrogen.

PMID- 9913483
TI  - Laser-induced fluorescence measurements of resonance broadening in xenon.

PMID- 9913484
TI  - Convergence behavior of multireference perturbation theory: Forced degeneracy and
      optimization partitioning applied to the beryllium atom.

PMID- 9913485
TI  - Positronium formation in positron-alkali-metal-atom collisions: An optical
      potential approach.

PMID- 9913486
TI  - Finite-element calculations for the three-body Coulomb problem with two equal
      masses.

PMID- 9913488
TI  - X-ray resonant scattering involving dissociative states.

PMID- 9913487
TI  - Energies and radiative and nonradiative decay rates of doubly excited 3lnl' and
      4lnl' (n >= 4) states in Ne8+

PMID- 9913489
TI  - Adiabatic hyperspherical study of the helium trimer.

PMID- 9913491
TI  - Stochastic realization shift in the ground-state hyperfine transition of an
      alkali-metal vapor.

PMID- 9913490
TI  - Collisional broadening and shifting parameters of the Raman Q branch of H2
      perturbed by N2 determined from speed-dependent line profiles at high
      temperatures.

PMID- 9913492
TI  - Symmetry of approximate Hamiltonians generated in Birkhoff-Gustavson normal form.

PMID- 9913493
TI  - Single-electron capture by hydrogen atoms and helium ions from helium atoms.

PMID- 9913494
TI  - Electron-impact cross sections involving electronically excited states in H2
      molecules: B 1 Sigma +u-->I 1 Pi g transition.

PMID- 9913495
TI  - Triply differential cross section for ionization in ion-atom collisions.

PMID- 9913496
TI  - Contribution of excitation autoionization to the electron-impact ionization of
      Ar7+

PMID- 9913497
TI  - Diffusion of barium atoms in the 6s5d 3DJ metastable levels and the 6s2 1S0
      ground state through noble-gas perturbers.

PMID- 9913498
TI  - Measurement of the contributions of high-n satellite lines to the K beta lines of
      He-like Ar16+

PMID- 9913499
TI  - Calculation of the electron-proton scattering cross sections in a strongly
      magnetized plasma.

PMID- 9913500
TI  - Mean lifetime measurements of HeH2+(2p sigma ) isotopes.

PMID- 9913501
TI  - Azimuthal asymmetry in elastic electron scattering by polarized 3P sodium atoms.

PMID- 9913502
TI  - Evolution from spectator to normal Auger lines through the thresholds observed in
      the Ca 3p excitation region.

PMID- 9913503
TI  - Collinear electron-helium-ion collisions: Chaotic scattering dominated by triple
      collision orbits.

PMID- 9913506
TI  - Branching and anisotropy of barrier tunneling and fluorescent decay in H2. I.
      Experiment.

PMID- 9913505
TI  - Polarization studies of rare-gas resonance radiation: Argon, krypton, and xenon.

PMID- 9913504
TI  - Single- and double-electron loss of H- in collisions with SF6, CH4, and CO.

PMID- 9913508
TI  - Hyperspherical theory of three-particle fragmentation and Wannier's threshold
      law.

PMID- 9913510
TI  - Quasiclassical-trajectory Monte Carlo methods for collisions with two-electron
      atoms.

PMID- 9913507
TI  - Branching and anisotropy of barrier tunneling and fluorescent decay in H2. II.
      Theory.

PMID- 9913509
TI  - Two-dimensional R-matrix propagator: Application to electron-hydrogen scattering.

PMID- 9913511
TI  - Electron-impact single ionization of low-charged molybdenum ions.

PMID- 9913512
TI  - Numerical solution of the time-dependent Schrodinger equation for intermediate
      energy collisions of antiprotons with hydrogen.

PMID- 9913513
TI  - Angular anisotropy of the Kr 3d3/2,5/2-15p-->4p-25p resonant Auger decay studied
      by utilizing the Auger resonant Raman effect.

PMID- 9913514
TI  - Consistency test of double ionization of helium by photons and charged particles.

PMID- 9913515
TI  - The L gamma 1,5, L gamma 2,3,(6), L gamma 4, and L alpha x-ray fluorescence cross
      sections for the elements with 71 <~ Z <~ 83 at 22.6 keV.

PMID- 9913516
TI  - Dielectronic recombination and energy loss for He-like 79Br ions channeled in a
      thin single crystal of Si.

PMID- 9913518
TI  - Projectile velocity and target temperature dependence of charge-state
      distributions of multicharged ions scattered during grazing interactions with a
      Au(110) surface.

PMID- 9913517
TI  - Energy loss of ions moving near a solid surface.

PMID- 9913519
TI  - Interferometer for cold neutrons using multilayer mirrors.

PMID- 9913520
TI  - Nonclassical spatial and momentum distributions in a Bose-condensed gas.

PMID- 9913521
TI  - Bose-Einstein condensation of a finite number of particles trapped in one or
      three dimensions.

PMID- 9913523
TI  - Theoretical studies of electronic excited states for Na3.

PMID- 9913522
TI  - Role of attractive interactions on Bose-Einstein condensation.

PMID- 9913524
TI  - 3n+l quantum number in the cluster problem.

PMID- 9913526
TI  - Two-dimensional quantum hydrogen atom in circularly polarized microwaves: Global
      properties.

PMID- 9913525
TI  - Quantum-statistical enhancement of spontaneous emission in velocity-selective
      coherent population trapping: Mean-field calculations.

PMID- 9913528
TI  - Effect of the ponderomotive potential on atomic energy differences.

PMID- 9913527
TI  - Perturbative formulation of optimal control for two-photon transitions: Reduction
      to an eigenvalue problem.

PMID- 9913529
TI  - Phase dependence of (N+1)-color (N>1) ir-uv photoionization of atoms with higher
      harmonics.

PMID- 9913530
TI  - Entropic measure of wave-packet spreading and ionization in laser-driven atoms.

PMID- 9913531
TI  - Enhanced ionization of diatomic molecules in strong laser fields: A classical
      model.

PMID- 9913532
TI  - Coulomb corrections and polarization effects in high-intensity high-harmonic
      emission.

PMID- 9913533
TI  - Influence of resonant pulse propagation on collision-induced stimulated effects
      in the S1/2-P1/2,3/2 system.

PMID- 9913534
TI  - Dye laser with pump and quantum noise.

PMID- 9913535
TI  - Master-equation theory of multimode semiconductor lasers.

PMID- 9913536
TI  - Amplification without population inversion in a

PMID- 9913537
TI  - Performance of a dual recycled interferometer with squeezed light.

PMID- 9913538
TI  - Propagation of laser pulses and coherent population transfer in dissipative three
      level systems: An adiabatic dressed-state picture.

PMID- 9913539
TI  - Quantum state reconstruction and detection of quantum coherences on different
      observation levels.

PMID- 9913540
TI  - Conditional generation of special states using continuous measurements.

PMID- 9913541
TI  - Propagation of squeezed-light pulses in dispersive and absorbing linear
      dielectrics.

PMID- 9913542
TI  - Quantum-state homodyne measurement with vacuum ports.

PMID- 9913543
TI  - Coupled-mode calculation of K/2 spatial subharmonics in photorefractive moving
      gratings.

PMID- 9913544
TI  - Propagation of light beams in anisotropic nonlinear media: From symmetry breaking
      to spatial turbulence.

PMID- 9913545
TI  - Hydrodynamic phenomena in laser physics: Modes with flow and vortices behind an
      obstacle in an optical channel.

PMID- 9913546
TI  - Two-photon interference in optical fiber multiports.

PMID- 9913547
TI  - Nonlinear dynamics of a passive, coherently driven mesoscopic micromaser.

PMID- 9913548
TI  - Dicke superradiance and stimulated electronic Raman scattering of indium.

PMID- 9913549
TI  - Resonant degenerate four-wave mixing in dense media.

PMID- 9913550
TI  - Loss of spectral memory in the relaxation oscillations of a multimode solid-state
      laser.

PMID- 9913551
TI  - Light scattering by an ultracold trapped atom.

PMID- 9913553
TI  - Gaussian effective potential: Computation of eigenvalues.

PMID- 9913552
TI  - Vibrational amplification by stimulated emission of radiation.

PMID- 9913554
TI  - Exactness of the supersymmetric WKB approximation scheme.

PMID- 9913556
TI  - Representations of two-mode squeezing transformations.

PMID- 9913555
TI  - Spatial asymmetry in the photofragmentation of diatomic molecules using coherent
      control.

PMID- 9913557
TI  - Convexity and the translational-invariance constraint on the exchange-correlation
      functional.

PMID- 9913558
TI  - Diffusion quantum Monte Carlo calculation of the binding energy of positronium
      hydroxide.

PMID- 9913559
TI  - Molecular treatment of electron detachment in H++H- collisions.

PMID- 9913560
TI  - Left-right scattering asymmetries for electron transfer from oriented and tilted
      aligned Na(3p) states to H(n=2,3).

PMID- 9913562
TI  - Relaxation and generation of hyperfine coherences in an optically pumped heavy
      alkali-metal vapor undergoing double-resonance excitation.

PMID- 9913561
TI  - 3p photoabsorption of manganese

PMID- 9913564
TI  - Erratum: Transition to space-time chaos in a nonlinear optical system with two
      dimensional feedback

PMID- 9913563
TI  - Erratum: Evolution of coherences and populations in the secular approximation

PMID- 9913565
TI  - Postselection-free energy-time entanglement.

PMID- 9913566
TI  - Radiative lifetime of the 2P state of lithium.

PMID- 9913567
TI  - Superelastic electron scattering on lithium.

PMID- 9913568
TI  - Electron-capture cross section at near-thermal collision energies for Si4++D.

PMID- 9913570
TI  - Phase shift induced from the dc Stark effect in an atom interferometer comprised
      of four copropagating laser beams.

PMID- 9913569
TI  - Electron correlation in three-body Coulomb states of barium.

PMID- 9913571
TI  - Reconstructing the vibrational state of a trapped ion.

PMID- 9913572
TI  - Dipolar decay in two recent Bose-Einstein condensation experiments.

PMID- 9913573
TI  - Dynamics of Rydberg wave packets generated by half-cycle pulses.

PMID- 9913574
TI  - Observation of fractional revivals of a molecular wave packet.

PMID- 9913575
TI  - Efficient networks for quantum factoring.

PMID- 9913576
TI  - Decoherence and dephasing in a quantum measurement process.

PMID- 9913577
TI  - Relativistic electron moving in a multimode quantized radiation field.

PMID- 9913578
TI  - Good quantum error-correcting codes exist.

PMID- 9913580
TI  - Implications of the intrinsic decoherence in quantum mechanics to nonequilibrium
      statistical mechanics.

PMID- 9913579
TI  - Quantum ballistic evolution in quantum mechanics: Application to quantum
      computers.

PMID- 9913581
TI  - Calculation of the Aharonov-Bohm wave function.

PMID- 9913582
TI  - Nonintegral Maslov indices.

PMID- 9913583
TI  - Quantum measurement and the transformation from quantum to classical
      probabilities.

PMID- 9913584
TI  - Revivals of wave packets: General theory and application to Rydberg clusters.

PMID- 9913586
TI  - Scalar curvature factor in the Schrodinger equation and scattering on a curved
      surface.

PMID- 9913585
TI  - Generalized center-of-mass coordinate and relative momentum operators studied
      through unitary transformations.

PMID- 9913587
TI  - Formation of metastable dt micro molecules in t micro(2s)-D2 collisions.

PMID- 9913588
TI  - Stationary direct perturbation theory of relativistic corrections.

PMID- 9913589
TI  - Experimental gJ factor in the metastable 5D3/2 level of Ba+

PMID- 9913591
TI  - Approximate account of connected quadruply excited clusters in single-reference
      coupled-cluster theory via cluster analysis of the projected unrestricted Hartree
      Fock wave function.

PMID- 9913590
TI  - Direct calculation of Stark resonances in hydrogen.

PMID- 9913592
TI  - Resonant nuclear transition in the d micro 6Li muonic molecule.

PMID- 9913593
TI  - Corrections to O( alpha 7(ln alpha )mc2) fine-structure splittings and O( alpha
      6(ln alpha )mc2) energy levels in helium.

PMID- 9913594
TI  - Adiabatic potential-energy surfaces for higher excited states of the H2+ ion in a
      strong magnetic field.

PMID- 9913595
TI  - Second-order Zeeman effect in the 5 2S-3 2S and 4 2D-3 2S two-photon transitions
      of atomic sodium.

PMID- 9913596
TI  - Variational calculations of the Fermi contact term for the 2 2S, 2 2P, and 3 2S
      states of Li and the 2 2S state of Be+

PMID- 9913597
TI  - Local-density approximation, hierarchy of equations, functional expansion, and
      adiabatic connection in current-density-functional theory.

PMID- 9913598
TI  - Unresolved transition arrays and wave-number distributions for some E1
      transitions between high-l states of the iron-group elements.

PMID- 9913600
TI  - Relativistic many-body calculations of

PMID- 9913599
TI  - Polarization measurements on a magnetic quadrupole line in Ne-like barium.

PMID- 9913601
TI  - Threshold law for ionization of atomic hydrogen by positron impact.

PMID- 9913602
TI  - Analyticity and unitarity as constraints to obtain scattering phase shifts and an
      application to e-He scattering.

PMID- 9913603
TI  - Energy-pooling collisions in cesium: 6PJ+6PJ-->6S+(nl=7P,6D,8S,4F).

PMID- 9913604
TI  - Recoil-ion charge-state-resolved electron-production cross sections at 55 degrees
      for 1 MeV/u C5+ on He and Ar.

PMID- 9913605
TI  - Single ionization of He by low-velocity protons and C6+: Ejected electron
      momentum distributions.

PMID- 9913606
TI  - K-shell radiative electron capture with bare 60-MeV/u Kr ions channeled in a Si
      crystal: Experiments and simulations.

PMID- 9913607
TI  - Velocity-matching model for electron capture in keV atomic collisions.

PMID- 9913608
TI  - Line-shape analysis of resonant energy transfer collisions.

PMID- 9913609
TI  - Absolute cross sections for electron-impact single ionization of Neq+ (q=2,4-6)
      ions.

PMID- 9913610
TI  - Electron detachment of H- in collisions with multiply charged ions.

PMID- 9913611
TI  - Asymmetry parameter and momentum distribution of the nucleus in double
      photoionization of helium.

PMID- 9913612
TI  - Transfer-excitation processes in collisions of N3+ ions with H2, He, Ne, and Ar
      targets.

PMID- 9913613
TI  - Observation of oscillations of the optogalvanic signal in an electrodeless
      discharge.

PMID- 9913614
TI  - Measuring nondipolar asymmetries of photoelectron angular distributions.

PMID- 9913615
TI  - Dissociative ionization of H2 + by fast-electron impact: Use of a two-center
      continuum wave function.

PMID- 9913616
TI  - Parabolic-hyperspherical approach to the fragmentation of three-particle Coulomb
      systems.

PMID- 9913617
TI  - Basic matrix elements for level shifts and widths of hydrogenic levels in ion
      surface interactions.

PMID- 9913618
TI  - Spontaneous and stimulated combination scattering from alkali-metal Bose-Einstein
      condensates.

PMID- 9913620
TI  - Effect of noise and modulation on the reflection of atoms from an evanescent
      wave.

PMID- 9913619
TI  - Theory of two-photon adiabatic passage: Absorption to and emission from N states.

PMID- 9913622
TI  - High-order harmonic generation in a bichromatic elliptically polarized laser
      field.

PMID- 9913621
TI  - Double-core resonance in two-electron atoms.

PMID- 9913623
TI  - Trapped ions in the strong-excitation regime: Ion interferometry and nonclassical
      states.

PMID- 9913625
TI  - Quantum interferences in resonant multiphoton-ionization processes for a strongly
      coupled atomic system.

PMID- 9913624
TI  - Explosive ionization of molecules in intense laser fields.

PMID- 9913626
TI  - Coherent population transfer in multilevel systems with magnetic sublevels. III.
      Experimental results.

PMID- 9913627
TI  - Multiphoton ionization of H2+

PMID- 9913628
TI  - Resonant formation of Ca+ from the Ca*(4s25d1D2) level explained by
      autoionization through the 3d3/29f5/2, J pi =2(-) resonance.

PMID- 9913629
TI  - Effective Raman theory for a three-level atom in the Lambda configuration.

PMID- 9913630
TI  - Optical angular-momentum transfer to trapped absorbing particles.

PMID- 9913632
TI  - Atomic coherence and bistable lasers without inversion.

PMID- 9913631
TI  - Coherence and bandwidth measurements of harmonics generated from solid surfaces
      irradiated by intense picosecond laser pulses.

PMID- 9913633
TI  - Transverse patterns in degenerate optical parametric oscillation and degenerate
      four-wave mixing.

PMID- 9913634
TI  - Quantum noise reduction in stationary superradiance.

PMID- 9913635
TI  - Intensity phase coherence in three-mode Fabry-Perot lasers.

PMID- 9913636
TI  - Role of optical anisotropies in the polarization properties of surface-emitting
      semiconductor lasers.

PMID- 9913637
TI  - Quantum-optical input-output relations for dispersive and lossy multilayer
      dielectric plates.

PMID- 9913638
TI  - Direct sampling of density matrices in field-strength bases.

PMID- 9913639
TI  - Trapped ions as vibrational beam splitters: SU(2) states in a two-dimensional ion
      trap.

PMID- 9913640
TI  - Spontaneous emission from the bare ground state of an optically driven three
      level atom: Perturbation theory and energy conservation.

PMID- 9913641
TI  - Derivation and physical interpretation of the optimum detection operators for
      coherent-state signals.

PMID- 9913642
TI  - Phase-modulation effects in self-diffraction.

PMID- 9913643
TI  - Nonlinear oscillator behavior in the Jaynes-Cummings model.

PMID- 9913644
TI  - Relation between quantum computing and quantum controllability.

PMID- 9913645
TI  - Analysis of the He-Xe absorption spectrum in the far infrared.

PMID- 9913646
TI  - Unusual nature of positronium-proton elastic scattering.

PMID- 9913647
TI  - Calculation of electron-Cs scattering at intermediate energies.

PMID- 9913648
TI  - Simple calculation of the spatial evolution of atoms in a trap during occurrence
      of Bose-Einstein condensation.

PMID- 9913649
TI  - Josephson cascade micromaser.

PMID- 9913650
TI  - Comment on "Why quantum mechanics cannot be formulated as a Markov process"

PMID- 9913651
TI  - Reply to "Comment on 'Why quantum mechanics cannot be formulated as a Markov
      process"'

PMID- 9913652
TI  - Erratum: Simultaneous trapping of two different atomic species in a vapor-cell
      magneto-optical trap

PMID- 9913653
TI  - Group-theoretic intrepetation of the bound states of Morse oscillators.

PMID- 9913654
TI  - Natural widths in open-shell atoms: The K absorption spectrum of atomic oxygen.

PMID- 9913655
TI  - Calculation of double photoionization of helium using the convergent close
      coupling method.

PMID- 9913656
TI  - Convergent R matrix with pseudostates calculation for e--He collisions.

PMID- 9913657
TI  - S-wave model for electron-hydrogen scattering.

PMID- 9913658
TI  - Direct measurement of the ground-state dissociation energy of Na2.

PMID- 9913659
TI  - Millihertz magnetic resonance spectroscopy of Cs atoms in body-centered-cubic
      4He.

PMID- 9913661
TI  - Rotating magnetic quadrupole field traps for neutral atoms.

PMID- 9913660
TI  - Dark pair coherent states of the motion of a trapped ion.

PMID- 9913663
TI  - Phase-matched frequency conversion in ionizing atomic gases.

PMID- 9913662
TI  - Dynamics of electronic wave packets in field emission and intense-field laser
      atom physics.

PMID- 9913664
TI  - Trap-depth measurements using ultracold collisions.

PMID- 9913666
TI  - Temporal Bell-type inequalities for two-level Rydberg atoms coupled to a high-Q
      resonator.

PMID- 9913665
TI  - Entangled entanglement.

PMID- 9913667
TI  - Semiclassical approximations to the coherent-state propagator for a particle in a
      box.

PMID- 9913668
TI  - From Heisenberg matrix mechanics to semiclassical quantization: Theory and first
      applications.

PMID- 9913669
TI  - Information-theoretic aspects of inseparability of mixed states.

PMID- 9913670
TI  - Quantum copying: Beyond the no-cloning theorem.

PMID- 9913671
TI  - Higher-order binding corrections to the Lamb shift of 2P states.

PMID- 9913673
TI  - Classical information capacity of a quantum channel.

PMID- 9913672
TI  - Class of quantum error-correcting codes saturating the quantum Hamming bound.

PMID- 9913674
TI  - Electron correlation in momentum space for the neon-atom isoelectronic sequence
      from F- through Ar8+

PMID- 9913675
TI  - Crossed-field hydrogen atom and the three-body Sun-Earth-Moon problem.

PMID- 9913676
TI  - Extended time-dependent mean-field approximation.

PMID- 9913677
TI  - Kinetic-energy density functional: Atoms and shell structure.

PMID- 9913678
TI  - Contribution of electron correlation to the stability of dipole-bound anionic
      states.

PMID- 9913679
TI  - Kohn-Sham effective potentials for spin-polarized atomic systems.

PMID- 9913681
TI  - Density-matrix-functional calculations for matter in strong magnetic fields:
      Ground states of heavy atoms.

PMID- 9913680
TI  - Periodic-orbit spectra of hydrogen and helium.

PMID- 9913682
TI  - Measurement of five-photon decay in orthopositronium.

PMID- 9913683
TI  - Four-photon decay of orthopositronium: A test of charge-conjugation invariance.

PMID- 9913684
TI  - Effect of molecular dissociation on the exchange-correlation Kohn-Sham potential.

PMID- 9913685
TI  - Theoretical and experimental determination of the polarizabilities of the zinc
      1S0 state.

PMID- 9913687
TI  - alpha (Z alpha )2EF correction to hyperfine splitting in hydrogenic atoms.

PMID- 9913688
TI  - Experimental atomic transition probabilities for O

PMID- 9913686
TI  - Ground- and excited-state properties of neutral and anionic selenium dimers and
      trimers.

PMID- 9913689
TI  - Kinetic-energy- and angular-resolved fragmentation of CO in vibrational-resolved
      C 1s excitation.

PMID- 9913690
TI  - Modified Faddeev treatment of electron capture.

PMID- 9913691
TI  - Theory of slow-atom collisions.

PMID- 9913692
TI  - Radiative and inner-shell dielectronic recombination in a highly charged barium
      ion.

PMID- 9913693
TI  - Nuclear spin conversion in molecules: Experiments on 13CH3F support a mixing-of
      states model.

PMID- 9913694
TI  - Experimental thick-target bremsstrahlung spectra from collisions of 7.0-keV
      electrons with Ag and Au.

PMID- 9913695
TI  - Electron absorption by complex potentials: One-dimensional case.

PMID- 9913696
TI  - Narrow chaotic compound autoionizing states in atomic spectra.

PMID- 9913697
TI  - Partial photoionization cross sections and photoelectron angular distributions
      for double excitations up to the N=5 threshold in helium.

PMID- 9913699
TI  - Postcollision interactions in the Auger decay of the Ar L shell.

PMID- 9913701
TI  - Cross sections for the production of excited He+ (np) 2Po states by 50-150-keV
      proton impact on helium.

PMID- 9913698
TI  - Analysis of state-to-state differential cross sections in two-dimensional Xe-CO2
      scattering with long-range effects.

PMID- 9913700
TI  - Comparisons between perturbative and radiation-damped R-matrix approaches to
      dielectronic recombination: Application to Ar15+

PMID- 9913702
TI  - Core-to-Rydberg excitations and their Auger decay in the HCl and DCl molecules.

PMID- 9913703
TI  - Experimental determination of nondipolar angular distribution parameters for
      photoionization in the Ar K and Kr L shells.

PMID- 9913704
TI  - Angle-resolved Auger spectrum of the N2 molecule.

PMID- 9913705
TI  - Total ionization cross section for electron-hydrogen scattering using a time
      dependent close-coupling method.

PMID- 9913706
TI  - Absolute partial cross sections for electron-impact ionization of H2, N2, and O2
      from threshold to 1000 eV.

PMID- 9913707
TI  - Doubly differential cross sections of low-energy electrons emitted in the
      ionization of molecular hydrogen by bare carbon ions.

PMID- 9913708
TI  - Single- and double-electron detachment from H- in collisions with He.

PMID- 9913709
TI  - Interaction of spin-polarized atoms with a surface studied by optical-reflection
      spectroscopy.

PMID- 9913710
TI  - Index of refraction of noble gases for sodium matter waves.

PMID- 9913711
TI  - Interference of Bose condensates.

PMID- 9913712
TI  - Particle-hole excitations in small metal clusters by electron scattering.

PMID- 9913713
TI  - Interactions of the Na2 dimer with a C60 molecule.

PMID- 9913714
TI  - Relaxation processes in coherent-population trapping.

PMID- 9913715
TI  - H2 and D2 in intense sub-picosecond laser pulses: Photoelectron spectroscopy at
      1053 and 527 nm.

PMID- 9913717
TI  - Resonant photoionization of Ni

PMID- 9913716
TI  - Multipole moments and trap states in forward scattering of resonance light.

PMID- 9913718
TI  - Force measurement via dark-state cooling.

PMID- 9913719
TI  - Influence of laser fluctuations and spontaneous emission on the ring-shaped
      atomic distribution in a magneto-optical trap.

PMID- 9913721
TI  - Squeezed states in multiple atomic fluorescence.

PMID- 9913720
TI  - Magnetic inhibition of polarization-gradient laser cooling in sigma +- sigma -
      optical molasses.

PMID- 9913722
TI  - Field quantization in dielectric media and the generalized multipolar
      Hamiltonian.

PMID- 9913723
TI  - Theory of third-harmonic generation using Bessel beams, and self-phase-matching.

PMID- 9913724
TI  - Motion-quantized Jaynes-Cummings models with an arbitrary intensity-dependent
      medium.

PMID- 9913725
TI  - Optical dark resonance in multilevel systems with a treelike configuration.

PMID- 9913726
TI  - Spectral line shape of resonant four-wave mixing induced by broad-bandwidth
      lasers.

PMID- 9913727
TI  - Modal analysis of spontaneous emission in a planar microcavity.

PMID- 9913728
TI  - Optical-vortex pair creation and annihilation and helical astigmatism of a
      nonplanar ring resonator.

PMID- 9913729
TI  - Resonance fluorescence spectra of three-level atoms in a squeezed vacuum.

PMID- 9913730
TI  - Homodyne detection for the enhancement of antibunching.

PMID- 9913731
TI  - Two-mode quantum-optical state measurement: Sampling the joint density matrix.

PMID- 9913732
TI  - Observation of inversionless gain and field-assisted lasing in a nearly ideal
      three-level cascade-type atomic system.

PMID- 9913733
TI  - Enhanced input coupling into a gain-guided amplifier.

PMID- 9913734
TI  - Coherent and incoherent multiple-harmonic generation from metal surfaces.

PMID- 9913735
TI  - Quantum optics of plasmon polaritons and velocity sum rules.

PMID- 9913736
TI  - Application of a photon configuration-space model to soliton propagation in a
      fiber.

PMID- 9913737
TI  - Analytic solutions of the Bloch equation involving asymmetric amplitude and
      frequency modulations.

PMID- 9913738
TI  - Velocity-selective population and quantum collapse-revival phenomena of the
      atomic motion for a motion-quantized Raman-coupled Jaynes-Cummings model.

PMID- 9913739
TI  - Balance equations and threshold conditions for the inversionless laser in an
      autoionizing system.

PMID- 9913740
TI  - Atomic two-photon excitation by an injected squeezed vacuum in a cavity.

PMID- 9913741
TI  - Spontaneous emission from an atom in a nonideal cavity: Application of a
      generalized master equation.

PMID- 9913742
TI  - Enhanced beam characteristics of a discharge-pumped soft-x-ray amplifier by an
      axial magnetic field.

PMID- 9913743
TI  - Eigenvalue spectrum of the independent-fermion kinetic-energy kernel.

PMID- 9913744
TI  - Direct measurement of macroscopic electric fields produced by collective effects
      in electron-impact experiments.

PMID- 9913746
TI  - Multiple ionization of argon atoms by intense laser pulses.

PMID- 9913745
TI  - Complete negative-ion conversion of halogen atoms and positive ions in surface
      scattering from KI(100).

PMID- 9913747
TI  - Avoided level crossings between s states and Stark states in Rydberg Rb atoms.

PMID- 9913748
TI  - Suppression of ionization due to a laser pulse.

PMID- 9913749
TI  - Reconstruction of the quantum state via position distribution and its time
      derivative.

PMID- 9913750
TI  - Spatial correlation effects in a laser.

PMID- 9913751
TI  - Radiation reaction in the stimulated emission from a gain sheet and its
      similarity to superradiance.

PMID- 9913752
TI  - Effect of atom pairs on the vacuum trapping state in micromasers: A Monte Carlo
      wave-function approach.

PMID- 9913753
TI  - Erratum: Nonadiabatic coefficients of long-range effective potentials and the
      Faraday effect

PMID- 9913754
TI  - Error prevention scheme with four particles.

PMID- 9913755
TI  - Variational calculation of energy levels in p-bar He+ molecular systems.

PMID- 9913756
TI  - Evolution of a Bose-condensed gas under variations of the confining potential.

PMID- 9913757
TI  - Theory of an atom laser.

PMID- 9913758
TI  - Generation of ultrashort pulses of harmonics.

PMID- 9913759
TI  - Energetic electrons in strong-field ionization.

PMID- 9913760
TI  - Generation and control of high harmonics by laser interaction with transmission
      electrons in a thin crystal.

PMID- 9913761
TI  - Laser cooling during velocity-selective adiabatic population transfer.

PMID- 9913762
TI  - Very low threshold whispering-gallery-mode microsphere laser.

PMID- 9913763
TI  - Relation between dynamic localization in crystals and trapping in two-level
      atoms.

PMID- 9913764
TI  - Coherent nonlinear optical spectroscopy using photon-number squeezed light.

PMID- 9913765
TI  - Observation of a laserlike transition in a microcavity exciton polariton system.

PMID- 9913766
TI  - Darboux-Witten techniques for the Demkov-Ostrovsky problem.

PMID- 9913767
TI  - Quantum-mechanical description of charged particles with spin 1/2 in the magnetic
      field outside of a rectilinear current filament.

PMID- 9913768
TI  - Implications of the noncrossing property of Bohm trajectories in one-dimensional
      tunneling configurations.

PMID- 9913769
TI  - Factoring in a dissipative quantum computer.

PMID- 9913770
TI  - Sending entanglement through noisy quantum channels.

PMID- 9913771
TI  - Quantum data processing and error correction.

PMID- 9913772
TI  - Schumacher's quantum data compression as a quantum computation.

PMID- 9913773
TI  - Quantum cryptographic network based on quantum memories.

PMID- 9913774
TI  - Effect of a rotating potential on a quantum particle.

PMID- 9913775
TI  - Stochastic path integrals and open quantum systems.

PMID- 9913776
TI  - Parity bit in quantum cryptography.

PMID- 9913777
TI  - Collective tests for quantum nonlocality.

PMID- 9913778
TI  - Strong-coupling QED in a sphere: Degeneracy effects.

PMID- 9913779
TI  - Stabilization of quantum states in quantum-optical systems.

PMID- 9913780
TI  - Measuring quantum states: Experimental setup for measuring the spatial density
      matrix.

PMID- 9913782
TI  - Fourth-order vacuum-polarization contribution to the Lamb shift.

PMID- 9913781
TI  - Quantum analysis of the susceptibility for identical atoms subjected to an
      external force with a tail.

PMID- 9913783
TI  - Upper bound of the accessible information and lower bound of the Bayes cost in
      quantum signal-detection processes.

PMID- 9913784
TI  - Optimum decision scheme with a unitary control process for binary quantum-state
      signals.

PMID- 9913785
TI  - Quantum and classical statistics of the electromagnetic zero-point field.

PMID- 9913786
TI  - Three disks in a row: A two-dimensional scattering analog of the double-well
      problem.

PMID- 9913787
TI  - Family of geometric phases.

PMID- 9913788
TI  - Consistent histories and quantum reasoning.

PMID- 9913789
TI  - Fine-structure effects on collisional broadening and shift of thallium two-photon
      lines.

PMID- 9913790
TI  - Environment dependence of spectral and dissipative properties of an open spin
      system.

PMID- 9913791
TI  - Absolute generalized oscillator strengths of 4s, 4s', 4p+4p' excitations of argon
      determined by the angle-resolved electron-energy-loss spectrometer.

PMID- 9913792
TI  - Ground-state energy of a two-electron atom as a function of lambda =1/Z: Singular
      points and asymptotic behavior.

PMID- 9913793
TI  - Near-threshold infrared photodetachment of Al-: A determination of the electron
      affinity of aluminum and the range of validity of the Wigner law.

PMID- 9913794
TI  - Second-order self-energy-vacuum-polarization contributions to the Lamb shift in
      highly charged few-electron ions.

PMID- 9913795
TI  - Dominant ion-core assignments for the Rydberg states of Xe2 dissociating to
      Xe+Xe*(6p,5d) by dispersive photoelectron spectroscopy.

PMID- 9913796
TI  - Variational calculations of dispersion coefficients for interactions among H, He,
      and Li atoms.

PMID- 9913797
TI  - High-resolution pre-edge structure in the inner-shell ionization threshold region
      of rare gases Xe, Kr, and Ar.

PMID- 9913798
TI  - Boundary-condition-determined wave function for the ground state of helium and
      isoelectronic ions.

PMID- 9913799
TI  - Relativistic many-body calculations of energies of n=2 states for boronlike ions.

PMID- 9913800
TI  - Fully relativistic calculations for the ground state of the AgH molecule.

PMID- 9913801
TI  - Bound electronic states in a statically screened electric-dipole potential.

PMID- 9913802
TI  - Angular distribution of Auger electrons in the decay of resonantly excited
      4d3/2,5/2-1 6p states in Xe.

PMID- 9913803
TI  - Electron correlation in the 3p44s state of Ar studied via the 2p54s resonant
      Auger spectra.

PMID- 9913805
TI  - Nonadiabatic phase-matrix method for vibrational excitation and dissociative
      attachment in electron-molecule scattering.

PMID- 9913804
TI  - Inelastic and quasielastic collisions of Rydberg atoms with the heavy rare-gas
      atoms.

PMID- 9913806
TI  - Theory of ion-pair formation in Rydberg-atom-ground-state-atom collisions at
      thermal energies.

PMID- 9913808
TI  - Formation and decay of Xe 4d-1 vacancies studied via electron-electron
      coincidence experiments.

PMID- 9913807
TI  - Two-electron processes in the ionization of H2 and D2 by fast protons.

PMID- 9913809
TI  - Double- and single-differential and total ionization cross sections for electron
      impact ionization of a helium atom.

PMID- 9913810
TI  - Absolute doubly differential single-ionization cross sections in p+He collisions.

PMID- 9913811
TI  - H type of hidden crossings in atomic collisions involving highly charged ions.

PMID- 9913813
TI  - Two-electron capture by He2+, Li3+, and B5+ in the independent-event model.

PMID- 9913814
TI  - Differential and integral cross sections for excitation of the electronic states
      of nitric oxide by low-energy electron impact: Observation of a 2 Pi r-->2 Phi
      excitation process.

PMID- 9913812
TI  - Distorted-wave cross sections for electron-impact ionization of Ar7+

PMID- 9913815
TI  - Nonperturbative treatment of the screened-Coulomb contribution of projectile
      electron loss.

PMID- 9913816
TI  - Calculation of ionization within the close-coupling formalism.

PMID- 9913817
TI  - Role of electron-ion recombination processes in the lifetime of stored D+ beams.

PMID- 9913818
TI  - L-subshell ionization studies in Au and Bi for 19F and 28Si large-ion
      bombardment.

PMID- 9913819
TI  - Na(3ps) excitation by impact of slow multiply charged ions.

PMID- 9913821
TI  - Theory of elastic scattering of particles in a static potential field.

PMID- 9913820
TI  - Charge transfer in collisions of B2+(2S,2P) and B3+(1S) ions with He atoms below
      200 keV.

PMID- 9913822
TI  - Computation of exchange probability in one-dimensional electron-hydrogen
      scattering.

PMID- 9913824
TI  - Transient and asymptotic effects in tunneling.

PMID- 9913823
TI  - Two-electron capture and stabilization in collisions of C6+ with rare-gas targets
      at low energy.

PMID- 9913827
TI  - Asymptotic wave function for three charged particles in the continuum.

PMID- 9913826
TI  - Dielectronic recombination rate coefficients for highly ionized Ni-like atoms.

PMID- 9913828
TI  - Dissociative recombination and dissociative excitation of 4HeH+: Absolute cross
      sections and mechanisms.

PMID- 9913825
TI  - Correction of substrate effect in the measurement of 8-25-keV electron-impact K
      shell ionization cross sections of Cu and Co elements.

PMID- 9913829
TI  - High-resolution experimental and theoretical study of singly and doubly excited
      resonances in ground-state photoionization of neon.

PMID- 9913830
TI  - Low-speed limit of Bohr's stopping-power formula.

PMID- 9913831
TI  - Generalized Thomas-Fermi-Weizsacker approach to screening and slowing down of
      swift charged particles in jellium.

PMID- 9913832
TI  - Energy loss of H+ and He+ in Al, Zn, and Au in the very low- to intermediate
      energy range.

PMID- 9913833
TI  - Charge state of 2-MeV carbon ions in the vicinity of a SnTe(001) surface.

PMID- 9913834
TI  - Photoatomic effect: Light-induced ejection of Na and Na2 from
      polydimethylsiloxane surfaces.

PMID- 9913835
TI  - Metastable Bose condensate made of atoms with attractive interaction.

PMID- 9913839
TI  - Ionization and fragmentation of C60 by highly charged, high-energy xenon ions.

PMID- 9913842
TI  - Radiative renormalization analysis of two-level systems with permanent dipole
      moments.

PMID- 9913840
TI  - Quantum fine structure of the optical Stern-Gerlach effect.

PMID- 9913837
TI  - Inertial sensing with classical atomic beams.

PMID- 9913841
TI  - Force, diffusion, and channeling in sub-Doppler laser cooling.

PMID- 9913838
TI  - Stimulated enhancement of cross section by a Bose-Einstein condensate.

PMID- 9913843
TI  - Multichannel spectrum of neutral particles trapped by a wire.

PMID- 9913836
TI  - Testing energy quantization at the level of 100 kHz by neutron crystal
      diffraction.

PMID- 9913844
TI  - Dissociative ionization of H2 + in an intense laser field: Charge-resonance
      enhanced ionization, Coulomb explosion, and harmonic generation at 600 nm.

PMID- 9913845
TI  - Higher harmonic generation at metal surfaces by powerful femtosecond laser
      pulses.

PMID- 9913847
TI  - Phase control of molecular ionization: H2 + and H3 2+ in intense two-color laser
      fields.

PMID- 9913846
TI  - Trap for polarized atoms based on light-induced drift.

PMID- 9913848
TI  - R-matrix Floquet description of multiphoton ionization of Li.

PMID- 9913849
TI  - Stationary states and their stability for a mixture of molecular gases under
      velocity-selective excitation.

PMID- 9913852
TI  - Cooling using velocity or mode selection for alkali-metal atoms.

PMID- 9913850
TI  - Autoionizing Rydberg wave packets.

PMID- 9913851
TI  - Molecules in intense laser fields: Enhanced ionization in a one-dimensional model
      of H2.

PMID- 9913854
TI  - Reversibility of bound-to-continuum transitions induced by a strong short laser
      pulse and the semiclassical uniform approximation.

PMID- 9913853
TI  - Ionization of Li Rydberg atoms by 8.5- and 18-GHz circularly polarized microwave
      fields.

PMID- 9913855
TI  - Motional quantum states of a trapped ion: Measurement and its back action.

PMID- 9913858
TI  - Maxwell-Bloch equations for spatially inhomogeneous semiconductor lasers. I.
      Theoretical formulation.

PMID- 9913859
TI  - Maxwell-Bloch equations for spatially inhomogeneous semiconductor lasers. II.
      Spatiotemporal dynamics.

PMID- 9913863
TI  - Two-photon selective reflection.

PMID- 9913856
TI  - Direct measurement of diffusion coefficients of cesium 6P3/2 and 6P1/2 excited
      state atoms in neon gas.

PMID- 9913857
TI  - Class of feasible quantum superpositions of squeezed and sub-Poissonian states.

PMID- 9913860
TI  - Fock states in a Kerr medium with parametric pumping.

PMID- 9913861
TI  - Master-equation theory of multimode semiconductor lasers. II. Injection locking.

PMID- 9913862
TI  - Optical dephasing by a random telegraph frequency modulation.

PMID- 9913865
TI  - Experimental test of modular noise propagation theory for quantum optics.

PMID- 9913864
TI  - Coherence-induced effects in pulse-pair propagation through absorbing media.

PMID- 9913866
TI  - Average intensity and bifurcations in a pulsed laser.

PMID- 9913868
TI  - Quantum radiation generated by a moving mirror in free space.

PMID- 9913867
TI  - Pump modulation of a two-mode Fabry-Perot laser: Influence of an internal
      resonance.

PMID- 9913869
TI  - Biconical emission of spatially mode-locked patterns with wave-number ratio sqrt
      2 in a ring cavity device.

PMID- 9913870
TI  - Statistical analysis of pulses in systems with random modulation through an
      instability point.

PMID- 9913874
TI  - Transition probabilities of atomic systems between moving walls.

PMID- 9913871
TI  - Cascading of quadratic nonlinearities: An analytical study.

PMID- 9913873
TI  - Photonic-well microcavities for spontaneous emission control.

PMID- 9913875
TI  - Direct and ghost interference in double-slit experiments with coincidence
      measurements.

PMID- 9913872
TI  - Optical pattern selection by a lateral wave-front shift.

PMID- 9913876
TI  - Optical bistability of semiconductor microcavities in the strong-coupling regime.

PMID- 9913877
TI  - Underlying simplicity of atomic population variations induced by a stochastic
      phase-fluctuating field.

PMID- 9913878
TI  - Cavity quantum electrodynamics between parallel dielectric surfaces.

PMID- 9913879
TI  - Theory and simulations of superluminal optical pulses in gain media.

PMID- 9913882
TI  - Stimulated Raman processes in optically dense, inhomogeneously broadened media.

PMID- 9913881
TI  - Quantum-state control by a single conditional measurement: The periodically
      switched Jaynes-Cummings model.

PMID- 9913884
TI  - Two simple expressions for the spontaneous emission factor beta.

PMID- 9913880
TI  - Modulational instability and critical regime in a highly birefringent fiber.

PMID- 9913883
TI  - Multilevel rate-equation analysis to explain the recent observations of
      limitations to optical limiting dyes.

PMID- 9913885
TI  - Quasiadiabatic approximation for a dense collection of two-level atoms.

PMID- 9913887
TI  - Cavity modified quantum beats.

PMID- 9913888
TI  - Spectral properties of a micromaser: Atomic-beam statistics and the field
      correlation function.

PMID- 9913889
TI  - Quantum gap solitons and soliton pinning in dispersive medium and photonic-band
      gap materials: Bethe-ansatz solution.

PMID- 9913890
TI  - Molecular Raman effect in an optical microcavity: A classical approach.

PMID- 9913891
TI  - Importance of population transfers in high-order harmonic-generation spectra.

PMID- 9913893
TI  - Sub-Doppler linewidth with electromagnetically induced transparency in rubidium
      atoms.

PMID- 9913886
TI  - Theory of one-dimensional quantum gap solitons.

PMID- 9913892
TI  - Theory of lasing in a multiple-scattering medium.

PMID- 9913894
TI  - Absence of classical and quantum mixing.

PMID- 9913895
TI  - Dipole and quadrupole polarizabilities of spherical anions: F-, Si-, and Cl-

PMID- 9913896
TI  - Angular distributions of O+ from O2 2+ produced by electron impact on O2.

PMID- 9913900
TI  - Effective action approach to high-order harmonic generation.

PMID- 9913898
TI  - Electron-impact detachment from the H- and O- negative ions.

PMID- 9913897
TI  - Relating data for charged particle scattering, photoannihilation, and Compton
      scattering.

PMID- 9913899
TI  - Spontaneous thermal isomerization in isolated alkali-halide clusters.

PMID- 9913901
TI  - Number of phases required to determine a quantum state in optical homodyne
      tomography.

PMID- 9913903
TI  - Polar factorization of Fourier phase operators in the coherent-state basis.

PMID- 9913902
TI  - Driven two-level atom: A simplified derivation.

PMID- 9913904
TI  - Broadband phase-noise squeezing of traveling waves in electromagnetically induced
      transparency.

PMID- 9913906
TI  - Erratum: Analytic Born completion in the calculation of electron-molecule
      differential cross sections

PMID- 9913905
TI  - Analysis of sub-Doppler linewidths in inversionless amplification.

PMID- 9913907
TI  - Anomalous asymmetry splittings in a molecule with internal rotation in the
      presence of classical chaos.

PMID- 9913908
TI  - Particle with arbitrary spin in the magnetic field of a linear current.

PMID- 9913909
TI  - Proposal for a mesoscopic cavity QED realization of the Greenberger-Horne
      Zeilinger state.

PMID- 9913911
TI  - Evidence for the spin-orbit-induced p4(1D2)md 2Fe resonances in atomic Br and Cl.

PMID- 9913910
TI  - Delta I=4 and Delta I=8 bifurcations in rotational bands of diatomic molecules.

PMID- 9913913
TI  - Off-resonance light scattering from Bose condensates in traps.

PMID- 9913912
TI  - Angular distribution for the elastic scattering of electrons from Na+ ions.

PMID- 9913914
TI  - Coulomb focusing in intense field atomic processes.

PMID- 9913915
TI  - Large-amplitude nuclear motions in the laser-induced Coulomb explosion of carbon
      dioxide molecules.

PMID- 9913916
TI  - Spatially dependent multiphoton multiple ionization.

PMID- 9913920
TI  - Introducing nonlinear gauge transformations in a family of nonlinear Schrodinger
      equations.

PMID- 9913919
TI  - Continuous wavelet transform analysis of one-dimensional quantum bound states
      from first principles.

PMID- 9913918
TI  - Quantum statistics of fundamental and higher-order coherent quantum solitons in
      Raman-active waveguides.

PMID- 9913922
TI  - Quantum tunneling in a dissipative system.

PMID- 9913921
TI  - Random walks, continuum limits, and Schrodinger's equation.

PMID- 9913917
TI  - Transient self-bending of laser beams in photorefractive crystals with drift
      nonlinearity.

PMID- 9913923
TI  - Unambiguous quantum measurement of nonorthogonal states.

PMID- 9913925
TI  - Nearly instantaneous alternatives in quantum mechanics.

PMID- 9913927
TI  - Change and uncertainty in quantum systems.

PMID- 9913924
TI  - Relativistic Coulomb problem: Analytic upper bounds on energy levels.

PMID- 9913926
TI  - Integration of the Heisenberg equations for inverse power-law potentials.

PMID- 9913930
TI  - Mixed-state entanglement and quantum error correction.

PMID- 9913932
TI  - Lower bounds to the first-order gradient corrections in the gradient expansion of
      the kinetic- and exchange-energy functionals.

PMID- 9913933
TI  - Hohenberg-Kohn density-functional theory as an implicit Poisson equation for
      density changes from summed fragment densities.

PMID- 9913936
TI  - Relativistic-configuration-interaction results for the hyperfine-structure
      constants of 133Cs

PMID- 9913928
TI  - Classical state sensitivity from quantum mechanics.

PMID- 9913934
TI  - Dielectronic recombination and excitation autoionization rate coefficients for
      potassiumlike Mo23+ to fluorinelike Mo33+

PMID- 9913929
TI  - Parity nonconservation in high-Z heliumlike ions.

PMID- 9913935
TI  - Teardrop bifurcation for Rydberg atoms in parallel electric and magnetic fields.

PMID- 9913938
TI  - Density-functional theory for excited states.

PMID- 9913937
TI  - Collisional propagation effects in collision-induced rotational spectra.

PMID- 9913931
TI  - K-LM and K-MM radiative Auger effect from Kr and Xe.

PMID- 9913940
TI  - Observation of the second 3 Pi u valence state of O2.

PMID- 9913939
TI  - Time-dependent variational principle and the effective action in density
      functional theory and Berry's phase.

PMID- 9913941
TI  - Kohn-Sham calculations with self-interaction-corrected local-spin-density
      exchange-correlation energy functional for atomic systems.

PMID- 9913942
TI  - Combination of the many-body perturbation theory with the configuration
      interaction method.

PMID- 9913943
TI  - Raman, non-Raman, and anti-Raman dispersion in resonant x-ray scattering spectra
      of molecules.

PMID- 9913944
TI  - Measurements of the ground-state ionization energy and wavelengths for the 1s21S0
      1snp1P1 (n=6-12) lines of Al

PMID- 9913945
TI  - Asymmetric (e,2e) study of the 100-eV ionization of the 3 sigma g and 1 pi u
      molecular orbitals of N2.

PMID- 9913947
TI  - Electron correlation in ion-atom collisions.

PMID- 9913946
TI  - Electron scattering by Fe

PMID- 9913949
TI  - H0+H2 and H0+O2 collisions at low kilo-electron-volt energies.

PMID- 9913948
TI  - Electron-impact excitation of the 1 1S-->3 1P and 1 1S-->4 1P transitions in
      helium.

PMID- 9913950
TI  - Partial densities of states, scattering matrices, and Green's functions.

PMID- 9913952
TI  - State-selective electron capture by 18-keV Kr8+ ions from laser-excited Rb*(15p
      25p) Rydberg atoms.

PMID- 9913953
TI  - Postcollision interaction effects induced by Auger cascades following Xe L3-shell
      ionization.

PMID- 9913951
TI  - Dissociative recombination of CH+: Cross section and final states.

PMID- 9913954
TI  - Search for H2- resonances in the detachment of H- by electron impact with a high
      resolution cooler ring.

PMID- 9913955
TI  - Radiative association of LiH(X 1 Sigma +) from electronically excited lithium
      atoms.

PMID- 9913956
TI  - Photodetachment cross section of H- in electric and magnetic fields with any
      orientation.

PMID- 9913957
TI  - Triangle amplitude with off-shell Coulomb T matrix for exchange reactions in
      atomic and nuclear physics.

PMID- 9913958
TI  - Electron energy distributions from multiple ionization in 20-120-keV H++Ar
      collisions.

PMID- 9913959
TI  - Effect of the configuration interaction between resonances for dielectronic
      recombination and resonant transfer excitation of Na-like ions.

PMID- 9913961
TI  - Semiempirical scaling laws for electron capture at low energies.

PMID- 9913960
TI  - Experimental determination of orbital and spin orientation of (Ar+)* formed in
      collisions.

PMID- 9913963
TI  - Above-surface potential sputtering of protons by highly charged ions.

PMID- 9913966
TI  - Observation of temporary-negative-ion states in condensed methanol via
      vibrational excitation induced by slow electron scattering.

PMID- 9913965
TI  - Transport of electrons induced by highly charged Ni (74 MeV/u) and Cu (9.6 MeV/u)
      ions in carbon: A study of target-thickness-dependent electron yields.

PMID- 9913964
TI  - Collective effects in the energy loss of large hydrogen clusters.

PMID- 9913967
TI  - Charge-state dependence of image-charge acceleration of convoy electrons in fast,
      grazing collisions of carbon ions with a silicon (100) surface.

PMID- 9913962
TI  - Decay of hollow atoms above and below a surface.

PMID- 9913968
TI  - Probing the linear and nonlinear excitations of Bose-condensed neutral atoms in a
      trap.

PMID- 9913969
TI  - Bose-Einstein condensation of atomic gases in a general harmonic-oscillator
      confining potential trap.

PMID- 9913972
TI  - Effect of the odd-photon destructive interference on laser-induced transparency
      and multiphoton excitation and ionization in rubidium.

PMID- 9913970
TI  - Quantized hydrodynamic model and the dynamic structure factor for a trapped Bose
      gas.

PMID- 9913973
TI  - Laser-induced steric effects in nonlinear processes from short laser pulses.

PMID- 9913971
TI  - Order parameter at the boundary of a trapped Bose gas.

PMID- 9913974
TI  - Theory of high-order sum and difference frequency mixing in a strong bichromatic
      laser field.

PMID- 9913975
TI  - Atomic-velocity class selection using quantum interference.

PMID- 9913976
TI  - Atom dynamics in multiple Laguerre-Gaussian beams.

PMID- 9913977
TI  - Phase dependence of intense-field ionization.

PMID- 9913978
TI  - Light-induced current in plasma.

PMID- 9913979
TI  - Elementary Sisyphus process close to a dielectric surface.

PMID- 9913981
TI  - Analytic results for the linear and nonlinear response of atoms in a trap with a
      model interaction.

PMID- 9913980
TI  - Ionization, dissociation, and level shifts of H2 + in a strong dc or low
      frequency ac field.

PMID- 9913982
TI  - Vibrational pair cat states.

PMID- 9913983
TI  - Harmonic-generation control.

PMID- 9913984
TI  - Electric-field modification of two-photon, two-color, quadrupole-dipole
      depolarization spectra in atomic Cs.

PMID- 9913985
TI  - Influence of radiative interatomic collisions on dark-state cooling.

PMID- 9913986
TI  - Inverse scattering transform analysis of Stokes-anti-Stokes stimulated Raman
      scattering.

PMID- 9913987
TI  - Numerical studies of the mesomaser.

PMID- 9913988
TI  - Intensity noise of injection-locked lasers: Quantum theory using a linearized
      input-output method.

PMID- 9913989
TI  - Intensity-noise properties of injection-locked lasers.

PMID- 9913991
TI  - Squeezing of cw light in a single-mode dispersive chi (2) medium.

PMID- 9913990
TI  - Harmonic generation by superintense light scattering from relativistic electrons.

PMID- 9913992
TI  - Quadrupole radiation of an atom in the vicinity of a dielectric microsphere.

PMID- 9913993
TI  - Correlation-induced spectral changes and energy conservation.

PMID- 9913994
TI  - Coupled ion pairs in solids under the influence of a coherent radiation field.

PMID- 9913996
TI  - Fokker-Planck equation in the good-cavity limit and single-atom optical
      bistability.

PMID- 9913995
TI  - Superradiant laser with partial atomic cooperativity.

PMID- 9913998
TI  - Grouping of antiphase oscillations in modulated multimode lasers.

PMID- 9913997
TI  - Isotopically selective atom counting using photon burst detection.

PMID- 9913999
TI  - Quantum images in double-slit experiments with spontaneous down-conversion light.

PMID- 9914000
TI  - Optical bistability and phase transitions in a doped photonic band-gap material.

PMID- 9914001
TI  - Polarizability effects in resonant ultrafast spectroscopy.

PMID- 9914002
TI  - Feedback-assisted homodyne detection of phase shifts.

PMID- 9914003
TI  - Nonclassical interferometry with intelligent light.

PMID- 9914004
TI  - Effect of feedback on the decoherence of a Schrodinger-cat state: A quantum
      trajectory description.

PMID- 9914005
TI  - Frequency-asymmetric gain profile in a seeded Raman amplifier.

PMID- 9914007
TI  - Resolutions of the identity in terms of SU(2) coherent states and their use for
      quantum-state engineering.

PMID- 9914006
TI  - Simple algebraic method to solve a coupled-channel cavity QED model.

PMID- 9914008
TI  - Quantum jumps in hydrogenlike systems.

PMID- 9914009
TI  - Nonlinear coherent states.

PMID- 9914010
TI  - Optimum phase-shift estimation and the quantum description of the phase
      difference.

PMID- 9914011
TI  - Diffusion quantum Monte Carlo calculations of positronium hydride and positron
      lithium.

PMID- 9914012
TI  - Cross sections of charge transfer between a Gd atom and its singly charged
      positive ion in metastable states close to the ground state.

PMID- 9914014
TI  - Swift-Hohenberg equation for optical parametric oscillators.

PMID- 9914013
TI  - Differential scattering of Na-Na in the subthermal energy range.

PMID- 9914015
TI  - Intense J=0-1 soft-x-ray lasing at 28.5 nm in neonlike chromium.

PMID- 9914016
TI  - Comment on "Theorem on nonclassical states"

PMID- 9914017
TI  - Erratum: Adiabatic density-functional perturbation theory

PMID- 9914018
TI  - Metastable states of antiprotonic helium in the energy range of the 2S and 2P
      states of helium: Hyperspherical analysis of the system.

PMID- 9914019
TI  - Electron-impact ionization of laser-excited sodium atom.

PMID- 9914020
TI  - Continuous observation of interference fringes from Bose condensates.

PMID- 9914022
TI  - Noncondensate atoms in a trapped Bose gas.

PMID- 9914021
TI  - Interference of two Bose-Einstein condensates with collisions.

PMID- 9914023
TI  - Properties of cold collisions of 39K atoms and of 41K atoms in relation to Bose
      Einstein condensation.

PMID- 9914024
TI  - Observation of flux enhancement in collisions between ultracold atoms.

PMID- 9914025
TI  - Control-laser-induced subnatural linewidths and quenching of spontaneous
      emission.

PMID- 9914026
TI  - Conditional probabilities for a single photon at a beam splitter.

PMID- 9914027
TI  - Second-harmonic generation and the orbital angular momentum of light.

PMID- 9914029
TI  - Quantum Zeno effect on atomic excitation decay in resonators.

PMID- 9914028
TI  - Anharmonicity of the vacuum Rabi peaks in a many-atom system.

PMID- 9914031
TI  - Quasiclassical dynamics in a closed quantum system.

PMID- 9914030
TI  - Teleportation of a cavity-radiation-field state: An alternative scheme.

PMID- 9914032
TI  - Time of arrival in quantum mechanics.

PMID- 9914033
TI  - Quantum kinematic theory of a point charge in a constant magnetic field.

PMID- 9914034
TI  - Quantum logic using polarized photons.

PMID- 9914035
TI  - General fidelity limit for quantum channels.

PMID- 9914036
TI  - Quantum phase amplification.

PMID- 9914037
TI  - Classical limit and quantum measurements in the detection of photons.

PMID- 9914038
TI  - Simple quantum error-correcting codes.

PMID- 9914040
TI  - Semiclassical perturbation approach to quantum reflection.

PMID- 9914039
TI  - Quantum tunneling in the Wigner representation.

PMID- 9914041
TI  - Applications of the complex geometric phase for metastable systems.

PMID- 9914043
TI  - Electronic energies of americium from multiconfiguration Dirac-Fock calculations.

PMID- 9914042
TI  - Relevance of relativistic exchange-correlation functionals and of finite nuclei
      in molecular density-functional calculations.

PMID- 9914044
TI  - Rydberg states about dipolar cores: The quantum dynamics of the long-range
      anisotropic interaction.

PMID- 9914045
TI  - Ab initio instanton molecular dynamics for the description of tunneling
      phenomena.

PMID- 9914046
TI  - Separation of the exchange-correlation potential into exchange plus correlation:
      An optimized effective potential approach.

PMID- 9914048
TI  - Dielectric screening in the Thomas-Fermi model.

PMID- 9914047
TI  - Theory of muon spin relaxation of gaseous C2H4Mu.

PMID- 9914049
TI  - Universal relationship between optical emission and absorption of complex
      systems: An alternative approach.

PMID- 9914050
TI  - Ramsey patterns for multiquantum transitions in fountain experiments.

PMID- 9914051
TI  - Stability of light positronic atoms: Quantum Monte Carlo studies.

PMID- 9914052
TI  - Two-photon Rabi oscillations.

PMID- 9914053
TI  - Expansions of the pair distribution function and the second-order density matrix
      in terms of homogeneous functionals.

PMID- 9914054
TI  - Highly excited charged two-body systems in a magnetic field: A perturbation
      theoretical approach to classical dynamics.

PMID- 9914055
TI  - Corrections to O( alpha 7mc2) fine-structure splittings in helium.

PMID- 9914056
TI  - Continuum-distorted-wave-final-state approximation in positron-hydrogenic atom
      (ion) collisions with positronium formation.

PMID- 9914057
TI  - One- and two-electron transitions in slow C5+-He collisions: Total and angle
      differential cross sections and coherence parameters.

PMID- 9914058
TI  - Nonrelativistic factorizable scattering theory and the Calogero-Sutherland model.

PMID- 9914060
TI  - Radiative electron capture and the photoelectric effect at high energies.

PMID- 9914059
TI  - Measurements of anomalous elastic scattering of 59.54-keV photons.

PMID- 9914061
TI  - Bound-free electron-positron pair creation in relativistic heavy-ion collisions
      as a charge-transfer process.

PMID- 9914062
TI  - Ionization in coplanar symmetric (e,2e) experiments of N2 and CO at intermediate
      energies.

PMID- 9914063
TI  - Absolute determination of zero-energy phase shifts for multiparticle single
      channel scattering: Generalized Levinson theorem.

PMID- 9914065
TI  - Resonance-enhanced dissociation of a molecular ion below its electronic
      excitation threshold.

PMID- 9914064
TI  - Generalized Levinson theorem: Applications to electron-atom scattering.

PMID- 9914066
TI  - Radiative decay of the HeH+(b 3 Sigma +) molecular ion.

PMID- 9914068
TI  - Dissociative recombination of H2 +: Product state information and very large
      cross sections of vibrationally excited H2 +

PMID- 9914067
TI  - Hyperspherical coupled-channel calculations of positronium formation in low
      energy positron-helium collisions.

PMID- 9914069
TI  - Elastic and inelastic processes in H++C2H2 collisions below the 1.5-keV regime.

PMID- 9914070
TI  - Measurements of energy losses of 10-MeV neutral hydrogen atoms in carbon foils.

PMID- 9914071
TI  - Wake effects on the energy loss as a function of the scattering angle for thin
      film-transmitted H2 + ions.

PMID- 9914072
TI  - Phase ordering kinetics of the Bose gas.

PMID- 9914074
TI  - Condensate fluctuations of a trapped, ideal Bose gas.

PMID- 9914073
TI  - Delayed choices in atom Stern-Gerlach interferometry.

PMID- 9914075
TI  - Stability of Bose condensed atomic 7Li.

PMID- 9914077
TI  - Quantized light lenses for atoms: The perfect thick lens.

PMID- 9914076
TI  - Refractive components for magnetic atom optics.

PMID- 9914079
TI  - Spin-rotation coupling in ferromagnetic clusters.

PMID- 9914078
TI  - Renormalization group theory of the three-dimensional dilute Bose gas.

PMID- 9914080
TI  - Entangled vibrational states in polyatomic molecules.

PMID- 9914081
TI  - Quantum nondemolition measurements of vibrational populations in ionic traps.

PMID- 9914082
TI  - Resonance-enhanced multiphoton-ionization photoelectron spectroscopy of even
      parity Rydberg states of atomic sulfur.

PMID- 9914083
TI  - Measurements on trapped laser-cooled ions using quantum computations.

PMID- 9914084
TI  - Selective excitation and structure in the continuum.

PMID- 9914085
TI  - Iterative results for multiwave mixing.

PMID- 9914086
TI  - Exchange reactions in intense infrared laser fields.

PMID- 9914087
TI  - Dynamics, correlations, and phases of the micromaser.

PMID- 9914089
TI  - Instability of a multimode oscillation in a photorefractive ring oscillator.

PMID- 9914088
TI  - Angular energy distribution and temporal evolution of pulses emitted from low-Z
      neonlike J=0-1 x-ray lasers.

PMID- 9914091
TI  - Spontaneous emission near an absorbing dielectric surface.

PMID- 9914090
TI  - Theory of laser-amplifier injection locking.

PMID- 9914092
TI  - Transverse-mode coupling in a Kerr medium.

PMID- 9914093
TI  - Coherent states for quantum systems with a trilinear boson Hamiltonian.

PMID- 9914094
TI  - Transit-time effects in coherent transient spectroscopy.

PMID- 9914095
TI  - Monte Carlo wave functions and nonlinear master equations.

PMID- 9914096
TI  - Tomographic reconstruction of the density operator from its normally ordered
      moments.

PMID- 9914098
TI  - Multilevel quantum beats: An analytical approach.

PMID- 9914097
TI  - Dual eigenkets of the Susskind-Glogower phase operator.

PMID- 9914099
TI  - Photorefractive phase-conjugate reflectivity enhancement due to linear
      absorption.

PMID- 9914100
TI  - Synchronization of chaotic laser mode dynamics.

PMID- 9914101
TI  - Tunneling in a cavity.

PMID- 9914103
TI  - Non-Markovian dynamics of the micromaser due to discrete and continuous non
      Poissonian pumping.

PMID- 9914102
TI  - Generation of atomic-squeezed states in an optical cavity with an injected
      squeezed vacuum.

PMID- 9914105
TI  - Transverse correlation in optical spontaneous parametric down-conversion.

PMID- 9914104
TI  - Decoherence by spontaneous emission in atomic-momentum transfer experiments.

PMID- 9914106
TI  - Spontaneous photon emission in isolated-core excited Rydberg systems and dynamics
      of electronic wave packets.

PMID- 9914107
TI  - Stimulated Raman scattering in helium with soft-x-ray laser radiation.

PMID- 9914108
TI  - Displaced squeezed number states: Position space representation, inner product,
      and some applications.

PMID- 9914109
TI  - Mode control and pattern stabilization in broad-area lasers by optical feedback.

PMID- 9914110
TI  - Wavelength dependence of coherently induced transparency in a Doppler-broadened
      cascade medium.

PMID- 9914112
TI  - Fock-state preparation from thermal cavity fields by measurements on resonant
      atoms.

PMID- 9914111
TI  - Propagation and amplitude correlation of pairs of intense pulses interacting with
      a double- Lambda system.

PMID- 9914113
TI  - Bound-state position and momentum densities and Slater sum for closed shells in a
      bare Coulomb field.

PMID- 9914115
TI  - Existence of an Ericson regime in stretched helium.

PMID- 9914114
TI  - Superpartner systems and semiunitary transformations in supersymmetric quantum
      mechanics.

PMID- 9914117
TI  - Gauge transformations for coupled-channel calculations applied to pair production
      in relativistic atomic collisions.

PMID- 9914116
TI  - Autoionization path of double Rydberg states in calcium.

PMID- 9914118
TI  - Single ionization of one- and two-electron atomic systems by electron impact.

PMID- 9914120
TI  - Interaction-induced dipole and absorption spectra of collisional He-Ar pairs.

PMID- 9914119
TI  - Electronic excitation of H2 by electron impact using soft norm-conserving
      pseudopotentials.

PMID- 9914121
TI  - Experimental antiproton nuclear stopping power in H2 and D2.

PMID- 9914122
TI  - Vortex waves in a cloud of Bose-Einstein-condensed, trapped alkali-metal atoms.

PMID- 9914123
TI  - Resonant atomic tunneling through a laser beam.

PMID- 9914124
TI  - Influence of surrounding dielectrics on the spontaneous emission of
      sulforhodamine B molecules.

PMID- 9914125
TI  - Third- and fifth-harmonic generation at the interfaces of glass and liquids.

PMID- 9914126
TI  - Erratum: Hyperspherical theory of three-particle fragmentation and Wannier's
      threshold law

PMID- 9914127
TI  - Theory for the ultrafast structural response of optically excited small clusters:
      Time dependence of the ionization potential.

PMID- 9914128
TI  - Femtosecond pump-probe photoelectron spectroscopy: Mapping of vibrational wave
      packet motion.

PMID- 9914129
TI  - Experimental evidence for dielectronic excitation producing Ne K vacancies in 35
      keV N7++Ne collisions.

PMID- 9914130
TI  - Inelastic scattering of quasifree electrons on O7+ projectiles.

PMID- 9914131
TI  - Product-state distributions in the dissociative recombination of 3HeD+ and 4HeH+

PMID- 9914132
TI  - Angular distributions near resonances: Effects of neighboring resonances and
      quantum interference.

PMID- 9914133
TI  - Coherent quantum tunneling between two Bose-Einstein condensates.

PMID- 9914134
TI  - Optical detection of the relative phase between two Bose-Einstein condensates.

PMID- 9914135
TI  - Condensate fraction and critical temperature of a trapped interacting Bose gas.

PMID- 9914136
TI  - Semianalytic treatment of two-color photoassociation spectroscopy and control of
      cold atoms.

PMID- 9914138
TI  - Intensity interference in Bragg scattering by acoustic waves with thermal
      statistics.

PMID- 9914139
TI  - Optimal frequency measurements with maximally correlated states.

PMID- 9914137
TI  - Polarizability of a hydrogenic state.

PMID- 9914140
TI  - Saturated output of a Ge

PMID- 9914141
TI  - Application of the coupled cluster method to the Jaynes-Cummings model without
      the rotating-wave approximation.

PMID- 9914142
TI  - Single-cell analyses of nitrergic neurons in simple nervous systems.
AB  - Understanding the role of the gaseous messenger nitric oxide (NO) in the nervous
      system is complicated by the heterogeneity of its nerve cells; analyses carried
      out at the single cell level are therefore important, if not critical. Some
      invertebrate preparations, most especially those from the gastropod molluscs,
      provide large, hardy and identified neurons that are useful both for the
      development of analytical methodologies and for cellular analyses of NO
      metabolism and its actions. Recent modifications of capillary electrophoresis
      (CE) allow the use of a small fraction of an individual neuron to perform direct,
      quantitative and simultaneous assays of the major metabolites of the NO
      citrulline cycle and associated biochemical pathways. These chemical species
      include the products of NO oxidation (NO2-/NO3-), l-arginine, l-citrulline, l
      ornithine, l-argininosuccinate, as well as selected NO synthase inhibitors and
      cofactors such as NADPH, biopterin, FMN and FAD. Diverse cotransmitters can also
      be identified in the same nitrergic neuron. The sensitivity of CE methods is in
      the femtomole to attomole range, depending on the species analysed and on the
      specific detector used. CE analysis can be combined with prior in vivo
      electrophysiological and pharmacological manipulations and measurements to yield
      multiple physiological and biochemical values from single cells. The
      methodologies and instrumentation developed and tested using the convenient
      molluscan cell model can be adapted to the smaller and more delicate neurons of
      other invertebrates and chordates.

PMID- 9914143
TI  - Eclosion hormone provides a link between ecdysis-triggering hormone and
      crustacean cardioactive peptide in the neuroendocrine cascade that controls
      ecdysis behavior.
AB  - Three insect peptide hormones, eclosion hormone (EH), ecdysis-triggering hormone
      (ETH) and crustacean cardioactive peptide (CCAP), have been implicated in
      controlling ecdysis behavior in insects. This study examines the interactions
      between these three peptides in the regulation of the ecdysis sequence. Using
      intracellular recordings, we found that ETH is a potent activator of the EH
      neurons, causing spontaneous action potential firing, broadening of the action
      potential and an increase in spike peak amplitude. In turn, electrical
      stimulation of the EH neurons or bath application of EH to desheathed ganglia
      resulted in the elevation of cyclic GMP (cGMP) levels within the Cell 27/704
      group (which contain CCAP). This cGMP production increases the excitability of
      these neurons, thereby facilitating CCAP release and the generation of the
      ecdysis motor program. Extracellular recordings from isolated nervous systems
      show that EH has no effect on nervous systems with an intact sheath. In
      desheathed preparations, in contrast, EH causes only the ecdysis motor output.
      The latency from EH application to ecdysis was longer than that after CCAP
      application, but shorter than that when ETH is applied to a whole central nervous
      system. These data, along with previously published results, support a model in
      which ETH causes pre-ecdysis behavior and at higher concentrations stimulates the
      EH neurones. EH release then facilitates the onset of ecdysis by enhancing the
      excitability of the CCAP neurons.

PMID- 9914144
TI  - Energetics of locomotion by the Australian water rat (Hydromys chrysogaster): a
      comparison of swimming and running in a semi-aquatic mammal.
AB  - Semi-aquatic mammals occupy a precarious evolutionary position, having to
      function in both aquatic and terrestrial environments without specializing in
      locomotor performance in either environment. To examine possible energetic
      constraints on semi-aquatic mammals, we compared rates of oxygen consumption for
      the Australian water rat (Hydromys chrysogaster) using different locomotor
      behaviors: swimming and running. Aquatic locomotion was investigated as animals
      swam in a water flume at several speeds, whereas water rats were run on a
      treadmill to measure metabolic effort during terrestrial locomotion. Water rats
      swam at the surface using alternate pelvic paddling and locomoted on the
      treadmill using gaits that included walk, trot and half-bound. Water rats were
      able to run at twice their maximum swimming velocity. Swimming metabolic rate
      increased with velocity in a pattern similar to the 'humps' and 'hollows' for
      wave drag experienced by bodies moving at the water surface. Metabolic rate
      increased linearly during running. Over equivalent velocities, the metabolic rate
      for running was 13-40 % greater than for swimming. The minimum cost of transport
      for swimming (2.61 J N-1 m-1) was equivalent to values for other semi-aquatic
      mammals. The lowest cost for running (2.08 J N-1 m-1) was 20 % lower than for
      swimming. When compared with specialists at the extremes of the terrestrial
      aquatic continuum, the energetic costs of locomoting either in water or on land
      were high for the semi-aquatic Hydromys chrysogaster. However, the relative costs
      for H. chrysogaster were lower than when an aquatic specialist attempts to move
      on land or a terrestrial specialist attempts to swim.

PMID- 9914145
TI  - Expression of olfactory receptors during development in Xenopus laevis.
AB  - A coordinated expression of tissue- and cell-specific genes during development is
      required to establish the complex functional organization of the vertebrate
      olfactory system. Owing to the unique features of its olfactory system and the
      well-characterized phases of its development, Xenopus laevis was chosen as a
      model organism to study the onset and the temporal and spatial patterns of
      expression of olfactory-specific genes. Using RT-PCR and in situ hybridization,
      it was found that expression of Xenopus olfactory marker protein and of class I
      receptors, which are thought to be responsible for the perception of water
      soluble odorants, was detectable as early as stage 32, less than 2 days after
      fertilization. In contrast, expression of class II receptors, which are thought
      to recognize airborne odours, was not detected before stage 49, approximately 12
      days after fertilization. The results indicate that the expression of olfactory
      receptors and marker protein is governed by temporally regulated cues during
      development.

PMID- 9914146
TI  - Micromechanics of the equine hoof wall: optimizing crack control and material
      stiffness through modulation of the properties of keratin.
AB  - Small-scale components of the equine hoof wall were tested to determine their
      mechanical roles in the morphological hierarchy. Macroscale tensile tests
      conducted on samples of the inner wall tubules and intertubular material showed a
      sixfold difference in mean initial stiffnesses (0.47 and 0.08 GPa, respectively),
      indicating that the inner wall tubules stiffen the wall along its longitudinal
      axis. The similarity in material properties of tubule and intertubular samples
      from the mid-wall suggests that tubules in this region offer only minor
      reinforcement along the longitudinal axis. Microscale tests conducted on rows of
      keratin strands from the inner wall tubules and intertubular material, and on
      intertubular keratin strands of the mid-wall, produced estimates of the
      stiffnesses of the hydrated matrix (0.03 GPa) and intermediate filament (IF; 3-4
      GPa) components of the nanoscale ( &agr; -keratin) composite. The results from
      these tests also suggest that the properties of the keratin composite vary
      through the wall thickness. Birefringence measurements on inner wall and mid-wall
      regions agree with these observations and suggest that, although the keratin IF
      volume fraction is locally constant, the volume fraction changes through the
      thickness of the wall. These findings imply that modulation of the hoof wall
      properties has been achieved by varying the IF volume fraction, countering the
      effects of specific IF alignments which serve another function and would
      otherwise adversely affect the modulus of a particular region.

PMID- 9914147
TI  - Kinematics and muscle dynamics of C- and S-starts of carp (Cyprinus carpio L.).
AB  - An analysis is presented of body curvature, acceleration and muscle strain during
      fast-starts in the common carp (Cyprinus carpio L.). C- and S-starts were filmed
      at 200 frames s-1 at 23 degreesC. Curvatures and accelerations of mid-body axes
      were calculated from digitised outlines. Maximum accelerations at 0.3 FL (fork
      length) from the snout were 54 m s-2 for C-starts and 40 m s-2 for S-starts. The
      total turning angle was approximately 150 degrees in C-starts. This angle was 70
      degrees during escape S-starts, significantly larger than for predatory S-starts
      in other species. Sarcomere strains of axial muscle fibres were calculated at 0.4
      and 0.8 FL. During C-starts, white muscle fibres were exposed to maximum
      sarcomere strains of up to approximately 16 %, and posterior fibres had similar
      strains to anterior fibres (red 27 %; white 16 %). During S-starts, however,
      maximum strains in anterior fibres (red 39 %; white 24 %) were more than twice
      those in posterior fibres (red 17 %; white 10 %). In a C-start, the fish made a
      large turning angle directed away from the stimulus by bending its tail strongly
      and thereby producing a large thrust. A larger anterior peak curvature of the
      fish during S-starts enabled the carp to control the direction of escape better
      than during C-starts, but with lower accelerations and smaller turning angles.
      During cyclic and intermittent swimming, red posterior fibres experienced the
      largest strains. Interestingly, previous studies have shown these fibres to have
      the lowest passive stiffness and the largest titin isoform, allowing them to
      attain large strain amplitudes with relatively low passive tensions.

PMID- 9914148
TI  - ATP reception and chemosensory adaptation in Tetrahymena thermophila.
AB  - Micromolar concentrations of adenosine triphosphate (ATP) and its non
      hydrolyzable analog &bgr;- &ggr; -methylene ATP are both effective depolarizing
      chemorepellents in Tetrahymena thermophila. Chemorepellent behavior consists of
      repeated bouts of backward swimming (avoidance reactions) that can easily be
      quantified to provide a convenient bioassay for purinergic reception studies.
      Chemosensory adaptation occurs following prolonged exposure (10 min) to the
      repellents, and cells regain normal swimming behavior. Adaptation is specific
      since cells that are behaviorally adapted to either ATP or &bgr;- &ggr; 
      methylene ATP still retain full responsiveness to the chemorepellents GTP and
      lysozyme. However, cross adaptation occurs between ATP and &bgr;- &ggr; 
      methylene ATP, suggesting that they involve the same receptor. Behavioral
      sensitivity to both ATP and &bgr;- &ggr; -methylene ATP is increased by the
      addition of Na+, but addition of either Ca2+ or Mg2+ dramatically decreases the
      response to ATP. These ionic effects are correlated with in vivo ATP hydrolysis,
      suggesting that divalent ions decrease purinergic sensitivity by activating a
      Ca2+- or Mg2+-dependent ecto-ATPase to hydrolyze the ATP signal. In vivo [32P]ATP
      binding studies and Scatchard analysis suggest that the behavioral adaptation is
      due to a decrease in the number of surface binding sites, as represented by
      decreased Bmax values. All these changes are reversible (de-adaptation) after 12
      min in a repellent-free buffer. Electrophysiological analysis showed that both
      &bgr;- &ggr; -methylene ATP (10 micromol l-1) and ATP (500 micromol l-1) elicited
      sustained, reversible depolarizations while GTP (10 micromol l-1) produced a
      transient depolarization, suggesting that the chemosensory response pathways for
      ATP and GTP reception may differ. There may be separate ATP and GTP receptors
      since ATP and GTP responses do not cross-adapt and 'cold' (unlabeled) GTP is not
      a good inhibitor of [32P]ATP binding. These results suggests that T. thermophila
      possess high-affinity surface receptors for ATP that are down-regulated during
      chemosensory adaptation. These ATP receptors may act as chemorepellent receptors
      to enable T. thermophila to recognize recently lysed cells and avoid a possibly
      deleterious situation. This is the simplest eukaryotic organism to show an
      electrophysiological response to external ATP.

PMID- 9914149
TI  - A comparison of the release of a vasoactive-intestinal-peptide-like peptide and
      acetylcholine in the giant axon-Schwann cell preparation of the tropical squid
      Sepioteuthis sepioidea.
AB  - A vasoactive intestinal peptide (VIP)-like peptide is released by axonal
      stimulation in the giant axon-Schwann cell preparation from the tropical squid
      Sepioteuthis sepioidea. It is also released by direct application of l-glutamate,
      the giant axon-Schwann cell signalling molecule in this preparation. The release
      of the peptide parallels the release of acetylcholine from the Schwann cells
      themselves in this preparation in a number of different ways. The release of both
      acetylcholine and the VIP-like peptide have the same threshold (between 2x10(-10)
      and 5x10(-10 )mol l-1) for l-glutamate application and the same recovery time
      after inhibition of release by exposure of the preparation to a prolonged pulse
      of l-glutamate. A prolonged l-glutamate pulse of 10(-8 )mol l-1 releases both
      substances for as long as the pulse is applied to the preparation, whereas a
      prolonged pulse of 10(-9 )mol l-1 l-glutamate releases acetylcholine in the same
      way but releases the VIP-like peptide only transiently. The VIP-like peptide is
      likely to be co-released with acetylcholine from the Schwann cells.

PMID- 9914150
TI  - P-type Ca2+ current in crayfish peptidergic neurones.
AB  - Inward Ca2+ current through voltage-gated Ca2+ channels was recorded from freshly
      dissociated crayfish X-organ (XO) neurones using the whole-cell voltage-clamp
      technique. Changing the holding potential from -50 to -90 mV had little effect on
      the characteristics of the current-voltage relationship: neither the time course
      nor the amplitude of the Ca2+ current was affected. Inactivation of the Ca2+
      current was observed over a small voltage range, between -35 and -10 mV, with
      half-inactivation at -20 mV. The activation of the Ca2+ current was modelled
      using Hodgkin-Huxley kinetics. The time constant of activation, &tgr; m, was
      568+/-66 micros at -20 mV and decreased gradually to 171+/-23 micros at 40 mV
      (means +/- s.e.m., N=5). The steady-state activation, m(infinity), was fitted
      with a Boltzmann function, with a half-activation voltage of -7.45 mV and an
      apparent threshold at -40 mV. The instantaneous current-voltage relationship was
      adjusted using the Goldman-Hodgkin-Katz constant-field equation, giving a
      permeation of 4.95x10(-5 )cm s-1. The inactivation of the Ca2+ current in XO
      neurones was dependent on previous entry of Ca2+. Using a double-pulse protocol,
      the inactivation was fitted to a U-shaped curve with a maximal inactivation of 35
      % at 30 mV. The time course of the recovery from inactivation was fitted with an
      exponential function. The time constants were 17+/-2.6 ms for a prepulse of 10 ms
      and 31+/-3.2 ms for a prepulse of 20 ms. The permeability sequence of the Ca2+
      channels was as follows: Ba2+>Sr2+~Ca2+>>Mg2+. Other divalent cations blocked the
      Ca2+ current, and their effects were voltage-dependent; the potency of blockage
      was Cd2+~Zn2+>>Co2+~Ni2+. The peptide &ohgr; -agatoxin-IVA, a selective toxin for
      P-type Ca2+ channels, blocked 85 % of the Ca2+ current in XO neurones at 200 nmol
      l-1, but the current was insensitive to dihydropyridines, phenylalkylamines,
      &ohgr; -conotoxin-GVIA and &ohgr; -conotoxin-MVIIC, which are blockers of L-, N-
      and Q-type Ca2+ channels, respectively. From the voltage- and Ca2+-dependent
      kinetics, the higher permeability to Ba2+ than to Ca2+ and the higher sensitivity
      of the current to Cd2+ than to Ni2+, we conclude that the Ca2+ current in XO
      neurones is generated by high-voltage-activated (HVA) channels. Furthermore, its
      blockage by &ohgr; -agatoxin-IVA suggests that it is mainly generated through P
      type Ca2+ channels.

PMID- 9914151
TI  - Fuel use in flight and its dependence on nectar feeding in the hawkmoth Amphion
      floridensis.
AB  - Fuel use varies widely among insects; however, the potential determinants of
      variation in fuel use have not been explored experimentally. This study examines
      whether fuel use during tethered flight depends upon feeding status in the
      nectarivorous hawkmoth Amphion floridensis. Fuel use in this study is
      characterized by the respiratory quotient, measured at intervals during a flight
      using modified closed-chamber respirometry. Moths were either fed twice daily to
      satiation with 30 % sucrose or unfed, and their fuel use was measured during
      flights on the first, third and fifth day after eclosion. Flights lasted up to 30
      min, with measurements taken at their onset and at 10 min intervals thereafter.
      Nectar feeding greatly affected fuel use in A. floridensis: fed moths relied
      primarily on carbohydrate, whereas unfed moths relied almost exclusively on fat
      reserves. Fuel use did not change during a flight, even when flights lasted 30
      min or more. Males were initially more extreme than females in their response to
      feeding treatment: they burned more carbohydrate when fed and more fat when
      unfed. By the third day after eclosion, however, fuel use in males and females
      became identical. Rates of oxygen consumption were uncorrelated with respiratory
      quotient, were higher in fed moths and declined during a flight. These data
      indicate that fuel use in this nectarivorous hawkmoth is flexible, that
      carbohydrate is important as a primary flight fuel and that an understanding of
      ecological factors, particularly foraging habit, is critical to understanding
      fuel use in insects.

PMID- 9914153
TI  - Cyclic AMP regulates PDGF-stimulated signal transduction and differentiation of
      an immortalized optic-nerve-derived cell line.
AB  - To facilitate the study of the molecular events underlying the development of
      optic-nerve-derived oligodendrocytes and their growth-factor-related signal
      transduction events, we immortalized perinatal rat optic nerve cells with a
      temperature-sensitive simian virus 40 large T-antigen, carrying the tsA58 and U19
      mutations, via a retrovirus vector. The line, tsU19-9, was selected on the basis
      of the expression of the neural precursor marker nestin. At the permissive
      temperature, 33 degreesC, tsU19-9 cells had a flat epithelial morphology. In
      contrast, following exposure to platelet-derived growth factor (PDGF), a factor
      important in the lineage progression of oligodendrocytes, or in the presence of
      dibutyryl cyclic AMP at 39 degreesC (the non-permissive temperature), the cells
      underwent morphological and antigenic differentiation to cells characteristic of
      the oligodendrocyte lineage. We used this cell line to investigate the binding
      characteristics of PDGF and related signalling cascades. Competition binding,
      phosphoinositide hydrolysis and intracellular Ca2+ mobilization assays all
      demonstrated that the three different isoforms of PDGF (AA, AB and BB) bound to
      and acted on the cell line. Overnight exposure to forskolin, a treatment that
      initiated morphological and phenotypic progression into an oligodendrocyte
      lineage, decreased PDGF-BB-induced intracellular Ca2+ mobilization and inhibited
      basal and PDGF-stimulated [3H]thymidine incorporation. Our results demonstrate
      that tsU19-9 may serve as a resource to study early optic-nerve oligodendrocyte
      development.

PMID- 9914154
TI  - Sexual behaviour in Euplotes raikovi is accompanied by pheromone-induced
      modifications of ionic currents.
AB  - In the marine ciliate Euplotes raikovi, pheromone released by a complementary
      mating type (nonself pheromone) induces typical sexual behaviour, whereas self
      pheromone released by the same mating type generally has no effect. Nonself
      pheromone evokes a reduction of the mean walking speed by 66 %, a threefold
      increase in the frequency and duration of long-lasting rest phases and a doubling
      in the number of side-stepping reactions. Consequently, translocation is strongly
      reduced and the cells remain in a small area. This could increase the probability
      of finding a sexual partner for pair formation (conjugation). The usual pattern
      of rhythmic, spontaneous depolarizations controlling the walking rhythm is absent
      in nonself-pheromone-stimulated cells. The remaining depolarizations arise from a
      4 mV hyperpolarized membrane potential and do not reach the usual amplitudes of
      15-20 mV but only of 6-10 mV. In addition, the amplitudes of K+ currents are
      increased at depolarizations of more than 20 mV by at least 30 %.
      Hyperpolarization- and depolarization-activated Na+ current amplitudes are
      increased, whereas the Ca2+ current amplitude remains nearly unaffected.

PMID- 9914152
TI  - Collagen-stimulated unidirectional translocation of cholesterol in human platelet
      membranes.
AB  - When human platelets are stimulated with collagen or thrombin, the asymmetric
      distribution of membrane lipids is disrupted as phosphatidylserine and
      phosphatidylethanolamine translocate from the inner monolayer to the outer
      monolayer. Coincident with the stimulus-dependent rearrangement of membrane
      phospholipids is a rapid redistribution of cholesterol from the outer to the
      inner membrane monolayer. This redistribution of cholesterol was observed when
      the stimulus was collagen or ADP. The data presented here show that epinephrine
      stimulation does not promote cholesterol translocation but does potentiate
      collagen-promoted movement of cholesterol. To investigate the process of
      cholesterol translocation, experiments were performed to determine whether
      collagen stimulated reverse cholesterol movement; i.e. from the inner to the
      outer monolayer. For this study, the fluorescent sterol cholestatrienol (C-3) was
      incorporated into platelet membranes by exchange from cholesterol-containing
      phosphatidylcholine small unilamellar vesicles. C-3 was then removed selectively
      from the outer monolayer by treatment of the platelets with bovine serum albumin
      (BSA). During the subsequent incubation of BSA-treated platelets, C-3 moved
      spontaneously into the outer from the inner monolayer. This translocation had an
      apparent half-time of approximately 25 min and was unaltered by the presence of
      collagen. These results suggest that collagen treatment of platelets selectively
      facilitates the inward movement of the sterol. We have hypothesized that
      cholesterol translocation may be thermodynamically driven as a result of an
      unfavorable entropy, resulting in cholesterol translocation out of an environment
      becoming enriched in phosphatidylethanolamine. The unidirectional nature of
      collagen-promoted cholesterol movement from the phosphatidylethanolamine-rich
      outer monolayer is consistent with this interpretation.

PMID- 9914155
TI  - Meiotic activation of rat pachytene spermatocytes with okadaic acid: the
      behaviour of synaptonemal complex components SYN1/SCP1 and COR1/SCP3.
AB  - The phosphatase inhibitor okadaic acid accelerates meiotic events in rodent germ
      cells in culture. Isolated pachytene spermatocytes treated with okadaic acid
      proceed to a metaphase I arrest in a few hours as opposed to the similar process
      in vivo, which requires several days. Leptotene/zygotene spermatocytes cannot be
      activated in this way, suggesting that okadaic acid enables cells to bypass a
      sensor of the meiotic progression, which is pachytene specific. We monitored the
      chromosome behaviour accompanying the transition to metaphase I in rat
      spermatocytes with antibodies against COR1/SCP3, a component of the meiotic
      chromosome cores, and against the synaptic protein, SYN1/SCP1. Okadaic acid
      induced a rapid synaptonemal complex dissolution and bivalent separation,
      followed by chromosome condensation and chiasmata formation, similar to the
      succession of events in untreated cells. The similarity between meiosis I induced
      with okadaic acid and the meiosis I events in vivo extends to the dissolution of
      the nuclear membrane and the disappearance of the microtubule network at the
      onset of metaphase I. This cell culture system provides a model for the in vivo
      transition from pachytene to metaphase I and therefore can be used in the study
      of this transition at the molecular level. The effect of okadaic acid is most
      likely mediated by the activation of tyrosine kinases, as addition of genistein,
      a general tyrosine kinase inhibitor, completely abolishes the observed effect of
      okadaic acid on chromosome metabolism. The okadaic acid-induced progression to
      the metaphase I arrest is not affected by the inhibition of protein synthesis.
      However, pachytene spermatocytes incubated in the presence of protein synthesis
      inhibitors for 6 hours show loss of synapsis which is abnormal in that it is not
      accompanied by chiasmata formation. The two meiosis-specific proteins, SYN1/SCP1
      and COR1/SCP3, are efficiently phosphorylated in vitro by extracts from isolated
      pachytene cells. Extracts from cells that have reached metaphase I upon okadaic
      acid treatment, with concomitant displacement of SYN1/SCP1 and COR1/SCP3 from
      their chromosomes, do not have this capability. These data support the hypothesis
      that phosphorylation of SYN1/SCP1 and COR1/SCP3 targets their removal from the
      chromosomes and that activity of the kinases involved correlates with the
      presence of these two proteins on the chromosomes.

PMID- 9914156
TI  - Induction of vascular smooth muscle cell tenascin-C gene expression by denatured
      type I collagen is dependent upon a beta3 integrin-mediated mitogen-activated
      protein kinase pathway and a 122-base pair promoter element.
AB  - Tenascin-C is an extracellular matrix glycoprotein, the expression of which is
      upregulated in remodeling arteries. In previous studies we showed that the
      presence of tenascin-C alters vascular smooth muscle cell shape and amplifies
      their proliferative response by promoting growth factor receptor clustering and
      phosphorylation. Moreover, we demonstrated that denatured type I collagen induces
      smooth muscle cell tenascin-C protein production via beta3 integrins. In the
      present study, we examine the pathway by which beta3 integrins stimulate
      expression of tenascin-C, and define a promoter sequence that is critical for its
      induction. On native collagen, A10 smooth muscle cells adopt a stellate
      morphology and produce low levels of tenascin-C mRNA and protein, whereas on
      denatured collagen they spread extensively and produce high levels of tenascin-C
      mRNA and protein, which is incorporated into an elaborate extracellular matrix.
      Increased tenascin-C synthesis on denatured collagen is associated with elevated
      protein tyrosine phosphorylation, including activation of extracellular signal
      regulated kinases 1 and 2 (ERK1 and ERK2). beta3 integrin function-blocking
      antibodies attenuate ERK1/2 activation and tenascin-C protein synthesis.
      Consistent with these findings, treatment with the specific MEK inhibitor, PD
      98059, results in suppression of tenascin-C protein synthesis. To investigate
      whether beta3 integrin-dependent activation of ERK1/2 regulates the tenascin-C
      promoter, we transfected A10 cells with a full-length (approx. 4 kb) mouse
      tenascin-C gene promoter-chloramphenicol acetyltransferse reporter construct and
      showed that, relative to native collagen, its activity is increased on denatured
      collagen. Next, to identify regions of the promoter involved, we examined a
      series of tenascin-C promoter constructs with 5' deletions and showed that
      denatured collagen-dependent promoter activity was retained by a 122-base pair
      element, located -43 to -165 bp upstream of the RNA start site. Activation of
      this element was suppressed either by blocking beta3 integrins, or by preventing
      ERK1/2 activation. These observations demonstrate that smooth muscle cell binding
      to beta3 integrins activates the mitogen activated protein kinase pathway, which
      is required for the induction of tenascin-C gene expression via a potential
      extracellular matrix response element in the tenascin-C gene promoter. Our data
      suggest a mechanism by which remodeling of type I collagen modulates tenascin-C
      gene expression via a beta3 integrin-mediated signaling pathway, and as such
      represents a paradigm for vascular development and disease whereby smooth muscle
      cells respond to perturbations in extracellular matrix composition by altering
      their phenotype and patterns of gene expression.

PMID- 9914157
TI  - TGFbeta1 induces a cell-cycle-dependent increase in motility of epithelial cells.
AB  - We have previously shown that addition of type 1 transforming growth factor-beta
      (TGFbeta1) to an exponentially growing population of mink lung CCl64 cells
      increases their average intermitotic time from 14.4 to 20.3 hours, predominantly
      by extending G1 from 7.5 to 13.5 hours. Here we have used the DRIMAPS system
      (digitally recorded interference microscopy with automatic phase-shifting) for
      obtaining data on cellular mass distribution, cell motility and morphology. We
      found no significant change in the cells' rate of mass increase following
      TGFbeta1 treatment, which implies that the treated cells attained a higher mass
      during their extended cell cycle and this was confirmed by direct measurement of
      cell size. However, the cells showed a dramatic motile response to treatment:
      TGFbeta1-treated cells had a significantly higher time-averaged speed of 36.2
      microm hour-1 compared to 14.5 microm hour-1 for the control cells. The time
      course of the response was gradual, reaching a maximum mean speed of 52.6 microm
      hour-1 after 15 hours exposure. We found that the gradual onset of the response
      was probably not due to a slow accumulation of a secondary factor but because
      cells were dividing throughout the experiment and most of the response to
      TGFbeta1 occurred only after the first cell division in its presence. Thus,
      taking only those cells that had not yet divided, the time-averaged speed of
      treated cells (26.1 micrometer hour-1) was only moderately higher than that of
      untreated cells (14.9 micrometer hour-1) whereas, for those cells that had
      divided, the difference in speed between treated cells (45.1 micrometer hour-1)
      and untreated cells (14.1 microm hour-1) was much greater. Increased speed was a
      consequence of enhanced protrusion and retraction of the cell margin coupled with
      an increase in cell polarity. TGFbeta1 also increased the mean spreading of the
      cells, measured as area-to-mass ratio, from 3.2 to 4.4 micrometer2 pg-1, and the
      intracellular mass distribution became more asymmetric. The observations indicate
      that a G2 signal may be necessary to reach maximal motility in the presence of
      TGFbeta1.

PMID- 9914158
TI  - The nucleolar phosphoprotein B23 redistributes in part to the spindle poles
      during mitosis.
AB  - B23 is a major phosphoprotein in the interphasic nucleolus where it is involved
      in the assembly of pre-ribosomes. Using several cultured animal cells, we report
      that, in addition to the known redistribution of the protein during mitosis, B23
      also becomes associated with mitotic spindle poles starting from early
      prometaphase onwards. Colocalization of B23 with the protein NuMA (Nuclear
      Mitotic Apparatus protein) was studied in mitotic cells and taxol-arrested cells.
      During the onset of mitosis, we observed that a fraction of B23 associates with,
      and dissociates from, the poles later than NuMA. At metaphase, both proteins are
      colocalized at the poles. The polar redistribution of both B23 and NuMA is
      mediated by microtubules. In taxol-treated cells, B23 is associated with the
      microtubule minus ends in the center of mitotic asters together with NuMA.
      Association of B23 with microtubule minus ends of mitotic asters was further
      confirmed with an in vitro assay, where B23 was found by western blotting to co
      sediment with taxol-induced microtubule asters formed in a mitotic cell extract.
      Immunolabeling demonstrated that B23 and NuMA were both present at the center of
      the asters. Furthermore, an additional hyperphosphorylated form of B23 appeared
      when microtubule asters formed and associated with the asters. Immunodepletion of
      B23 from the mitotic extract revealed that taxol-induced microtubule asters were
      still observed in B23-immunodepleted mitotic extract, indicating that the
      presence of B23 at the poles is unlikely to be essential for spindle formation or
      stabilisation.

PMID- 9914159
TI  - The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by
      Shiga-like toxin-1, during retrograde transport from the Golgi complex to the
      endoplasmic reticulum.
AB  - To investigate the role of the KDEL receptor in the retrieval of protein toxins
      to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing
      AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in
      toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the
      KDEL receptor was confirmed by immunofluorescence. When such cells were
      challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 (SLT
      1), there was no observable difference in their sensitivities as compared to
      cells which did not express these exogenous proteins. By contrast, the
      cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing lysozyme
      KDEL, which causes a redistribution of the KDEL receptor from the Golgi complex
      to the ER, and cells are sensitised to this toxin when they express additional
      KDEL receptors. These data suggest that, in contrast to SLT-1, PE can exploit the
      KDEL receptor in order to reach the ER lumen where it is believed that membrane
      transfer to the cytosol occurs. This contention was confirmed by microinjecting
      into Vero cells antibodies raised against the cytoplasmically exposed tail of the
      KDEL receptor. Immunofluorescence confirmed that these antibodies prevented the
      retrograde transport of the KDEL receptor from the Golgi complex to the ER, and
      this in turn reduced the cytotoxicity of PE, but not that of SLT-1, to these
      cells.

PMID- 9914160
TI  - N-Ras induces alterations in Golgi complex architecture and in constitutive
      protein transport.
AB  - Aberrant glycosylation of proteins and lipids is a common feature of many tumor
      cell types, and is often accompanied by alterations in membrane traffic and an
      anomalous localization of Golgi-resident proteins and glycans. These observations
      suggest that the Golgi complex is a key organelle for at least some of the
      functional changes associated with malignant transformation. To gain insight into
      this possibility, we have analyzed changes in the structure and function of the
      Golgi complex induced by the conditional expression of the transforming N
      Ras(K61) mutant in the NRK cell line. A remarkable and specific effect associated
      with this N-Ras-induced transformation was a conspicuous rearrangement of the
      Golgi complex into a collapsed morphology. Ultrastructural and stereological
      analyses demonstrated that the Golgi complex was extensively fragmented. The
      collapse of the Golgi complex was also accompanied by a disruption of the actin
      cytoskeleton. Functionally, N-Ras-transformed KT8 cells showed an increase in the
      constitutive protein transport from the trans-Golgi network to the cell surface,
      and did not induce the appearance of aberrant cell surface glycans. The Golgi
      complex collapse, the actin disassembly, and the increased constitutive secretion
      were all partially inhibited by the phospholipase A2 inhibitor 4-bromophenylacyl
      bromide. The results thus suggest the involvement of the actin cytoskeleton in
      the shape of the Golgi complex, and intracellular phospholipase A2 in its
      architecture and secretory function.

PMID- 9914161
TI  - Expression of A2B adenosine receptors in human lymphocytes: their role in T cell
      activation.
AB  - Extracellular adenosine has a key role in the development and function of the
      cells of the immune system. Many of the adenosine actions seem to be mediated by
      specific surface receptors positively coupled to adenylate cyclase: A2A and A2B.
      Despite the fact that A2A receptors (A2ARs) can be easily studied due to the
      availability of the specific agonist CGS21680, a pharmacological and
      physiological characterization of adenosine A2B receptors (A2BRs) in lymphocytes
      has not been possible due to the lack of suitable reagents. Here we report the
      generation and characterization of a polyclonal antipeptide antibody raised
      against the third extracellular loop of the A2BR human clone which is useful for
      immunocytochemical studies. This antibody has permitted the detection of A2BR+
      cells in lymphocyte samples isolated from human peripheral blood. The
      pharmacology of cAMP-producing compounds is consistent with the presence of
      functional A2BRs but not of A2A receptors in these human cells. The percentage of
      A2BR-expressing cells was similar in the CD4(+) or CD8(+) T cell subpopulations.
      Interestingly activation signals delivered by either phytohemagglutinin or anti-T
      cell receptor/CD3 complex antibodies led to a significant increase in both the
      percentage of cells expressing the receptor and the intensity of the labeling.
      These receptors are functional since interleukin-2 production in these cells is
      reduced by NECA but not by R-PIA or CGS21680. These results show that A2BR
      expression is regulated in T cell activation and suggest that the role of
      adenosine in lymphocyte deactivation is mediated by A2BRs.

PMID- 9914162
TI  - The Ku70 autoantigen interacts with p40phox in B lymphocytes.
AB  - Ku70, a regulatory component of the DNA-dependent protein kinase, was identified
      by a yeast two-hybrid screen of a B lymphocyte cDNA library as a partner of
      p40phox, a regulatory component of the O2--producing NADPH oxidase. Truncated
      constructs of p40phox and Ku70 were used to map the interacting sites. The 186 C
      terminal amino acids (aa) of Ku70 were found to interact with two distinct
      regions of p40phox, the central core region (aa 50-260) and the C-terminal
      extremity (aa 260-339). In complementary experiments, it was observed that Ku70
      binds to immobilized recombinant p40phox fusion protein and that p40phox and Ku70
      from a B lymphocyte cell extract comigrate in successive chromatographies on Q
      Separose, Superose 12 and hydroxylapatite columns. Moreover, we report that Ku70
      and p40phox colocalize in B lymphocytes and in transfected Cos-7 cells. We also
      show that the two NADPH oxidase activating factors, p47phox and p67phox are
      substrates for DNA-PK in vitro and that they are present together with p40phox in
      the nucleus of B cells. These results may help solve the paradox that the phox
      protein triad, p40phox, p47phox and p67phox, is expressed equally in B
      lymphocytes and neutrophils, whereas the redox component of the NADPH oxidase, a
      flavocytochrome b, which is well expressed in neutrophils, is barely detectable
      in B lymphocytes.

PMID- 9914163
TI  - Treatment of mammalian cells with the endoplasmic reticulum-proliferator
      compactin strongly induces recombinant and endogenous xenobiotic metabolizing
      enzymes and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro.
AB  - Some xenobiotics induce membrane-bound drug metabolizing enzymes (Xme) and a
      profound proliferation of the endoplasmic reticulum (ER) in vivo. However these
      effects are much weaker in vitro, possibly due to absence of certain
      transcription factors. We tested the possibility that ER proliferation can affect
      the level of ER-resident enzymes even in the absence of transcriptional
      activation. For this purpose we analysed the effects of compactin, which has been
      shown to induce ER proliferation in vitro, on recombinant Xme, which were
      expressed from a constitutive viral promoter. High levels of recombinant UDP
      glucuronosyltransferase UGT1A6 were achieved by amplification of the UGT1A6 cDNA
      using the dihydrofolate reductase cDNA as selectable marker in DHFR- CHO cells.
      Treatment of the resulting cell lines with lipoprotein-deficient serum in the
      absence and presence of compactin for 5 days resulted in a 1.3- and 2.3-fold,
      respectively, increase of the UGT enzyme activity towards 4-methylumbelliferone,
      paralleled by an induction of immunoreactive UGT1A6 protein. Similarly, treatment
      with this 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor increased the
      endogenous P450 reductase activity 2.6-fold, concomitant with an increase of
      immunodetectable protein. As expected compactin induced the level of 3-hydroxy-3
      methylglutaryl-CoA reductase. Increased levels of this protein have been
      associated with a proliferation of the ER. Compactin treatment of a separate cell
      line that expressed recombinant human P450 reductase increased this enzyme
      activity fivefold. Pulse-chase experiments revealed that the induction of the
      recombinant Xme by compactin was most likely due to decreased protein
      degradation. Our results show that enzyme systems unrelated to those involved in
      cholesterol biosynthesis are affected by compounds known to affect membrane
      biogenesis. Since this effect extends to heterologously expressed enzymes, it
      also provides an efficient means by which to increase the levels of recombinant
      ER proteins.

PMID- 9914164
TI  - Chromosomes exhibit preferential positioning in nuclei of quiescent human cells.
AB  - The relative spatial positioning of chromosomes 7, 8, 16, X and Y was examined in
      nuclei of quiescent (noncycling) diploid and triploid human fibroblasts using
      fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes and
      digital imaging. In quiescent diploid cells, interhomolog distances and
      chromosome homolog position maps revealed a nonrandom, preferential topology for
      chromosomes 7, 8 and 16, whereas chromosome X approximated a more random
      distribution. Variations in the orientation of nuclei on the culture substratum
      tended to hinder detection of an ordered chromosome topology at interphase by
      biasing homolog position maps towards random distributions. Using two chromosome
      X homologs as reference points in triploid cells (karyotype = 69, XXY), the
      intranuclear location of chromosome Y was found to be predictable within
      remarkably narrow spatial limits. Dual-FISH with various combinations of
      chromosome-specific DNA probes and contrasting fluorochromes was used to identify
      adjacent chromosomes in mitotic rosettes and test whether they are similarly
      positioned in interphase nuclei. From among the combinations tested, chromosomes
      8 and 11 were found to be closely apposed in most mitotic rosettes and interphase
      nuclei. Overall, results suggest the existence of an ordered interphase
      chromosome topology in quiescent human cells in which at least some chromosome
      homologs exhibit a preferred relative intranuclear location that may correspond
      to the observed spatial order of chromosomes in rosettes of mitotic cells.

PMID- 9914165
TI  - Intracellular localization and in vivo trafficking of p24A and p23.
AB  - Recently, p24A and p23 (also termed Tmp21), two members of the p24 protein
      family, have been proposed to function as integral receptors for the COPI-vesicle
      coat. This study describes the intracellular localization and trafficking of p24A
      in comparison to p23. For immunolocalization of p24A and p23, strong reduction
      and denaturation conditions were necessary to allow antibody interaction. Both
      p24A and p23 cycle continuously between intermediate compartment (IC) elements
      and the cis-Golgi network. In vivo trafficking of p24A and p23 tagged to green
      fluorescent protein (GFP) revealed that both proteins travel by large (up to 1
      micrometer in length) microtubule-dependent pre-Golgi carriers with a maximum
      speed of up to 1.6 micrometer s-1 from the IC to the Golgi cisternae. Aluminum
      fluoride, a general activator of heterotrimeric G-proteins, blocked peripheral
      pre-Golgi movements of GFP-p24A/p23 and inhibited fluorescence recovery after
      photobleaching in the perinuclear Golgi area. p24A and p23 are predominantly
      colocalized. Overexpression of GFP-p24A, to an extent which did not destroy the
      Golgi complex, induced delocalization of part of the proteins into ER elements.
      This study therefore gives new insights into the localization and trafficking
      behavior of the two COPI-binding proteins p24A and p23.

PMID- 9914166
TI  - Intracellular localization and membrane topology of 11-cis retinol dehydrogenase
      in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis
      retinaldehyde.
AB  - 11-cis retinol dehydrogenase (EC 1.1.1.105) catalyses the last step in the
      biosynthetic pathway generating 11-cis retinaldehyde, the common chromophore of
      all visual pigments in higher animals. The enzyme is abundantly expressed in
      retinal pigment epithelium of the eye and is a member of the short chain
      dehydrogenase/reductase superfamily. In this work we demonstrate that a majority
      of 11-cis retinol dehydrogenase is associated with the smooth ER in retinal
      pigment epithelial cells and that the enzyme is an integral membrane protein,
      anchored to membranes by two hydrophobic peptide segments. The catalytic domain
      of the enzyme is confined to a lumenal compartment and is not present on the
      cytosolic aspect of membranes. Thus, the subcellular localization and the
      membrane topology of 11-cis retinol dehydrogenase suggest that generation of 11
      cis retinaldehyde is a compartmentalized process.

PMID- 9914167
TI  - Reduced dosage of a single fission yeast MCM protein causes genetic instability
      and S phase delay.
AB  - MCM proteins are a conserved family of eukaryotic replication factors implicated
      in the initiation of DNA replication and in the discrimination between replicated
      and unreplicated chromatin. However, most mcm mutants in yeast arrest the cell
      cycle after bulk DNA synthesis has occurred. We investigated the basis for this
      late S phase arrest by analyzing the effects of a temperature-sensitive mutation
      in fission yeast cdc19(+ )(mcm2(+)). cdc19-P1 cells show a dramatic loss of
      viability at the restrictive temperature, which is not typical of all S phase
      mutants. The cdc19-P1 cell cycle arrest requires an intact damage-response
      checkpoint and is accompanied by increased rates of chromosome loss and mitotic
      recombination. Chromosomes from cdc19-P1 cells migrate aberrantly in pulsed-field
      gels, typical of strains arrested with unresolved replication intermediates. The
      cdc19-P1 mutation reduces the level of the Cdc19 protein at all temperatures. We
      compared the effects of disruptions of cdc19(+ )(mcm2(+)), cdc21(+ )(mcm4(+)),
      nda4(+ )(mcm5(+)) and mis5(+ )(mcm6(+)); in all cases, the null mutants underwent
      delayed S phase but were unable to proceed through the cell cycle. Examination of
      protein levels suggests that this delayed S phase reflects limiting, but not
      absent, MCM proteins. Thus, reduced dosage of MCM proteins allows replication
      initiation, but is insufficient for completion of S phase and cell cycle
      progression.

PMID- 9914168
TI  - Endothelial cell integrin alpha5beta1 expression is modulated by cytokines and
      during migration in vitro.
AB  - Alterations in endothelial cell-extracellular matrix interactions are central to
      the process of angiogenesis. We have investigated the effect of wound-induced two
      dimensional migration, basic fibroblast growth factor (bFGF), transforming growth
      factor-beta1 (TGF-beta1) and leukemia inhibitory factor (LIF) on expression of
      the alpha5beta1 integrin in endothelial cells. In multiple-wounded monolayers of
      bovine microvascular endothelial (BME) cells, an increase in mRNA and total
      protein for both alpha5 and beta1 subunits was observed, and this could be
      correlated with a reduction in cell density but not proliferation, both of which
      are induced following wounding. Although as previously reported, the alpha5
      subunit was increased when cells were exposed to TGF-beta1 alone, co-addition of
      bFGF and TGF-beta1 resulted in a striking synergistic induction of alpha5, with
      no significant changes in the expression of beta1. In contrast, the alpha5
      subunit was decreased by LIF in bovine aortic endothelial but not in BME cells.
      These findings suggest that quantitative alterations in alpha5 and beta1 integrin
      subunit expression modulate the adhesive and migratory properties of endothelial
      cells during angiogenesis.

PMID- 9914170
TI  - Connections between growth and the cell cycle.
AB  - To maintain a constant size during cellular proliferation, a cell's growth rate
      must match its rate of division. Factors that govern proliferation must therefore
      coordinately regulate two distinct processes: the cellular biosynthesis that
      drives accumulation of mass, and progression through the cell division cycle.
      Recent work has identified several mechanisms which couple cell division to
      growth. Different mechanisms are used at different times during development to
      coordinate growth, cell division, and patterning.

PMID- 9914169
TI  - Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on
      different haemopoietic cells.
AB  - Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM
      (A Disintegrin and Metalloprotease Domain) family of proteins and is widely
      expressed in different tissues and cell types. Members of this family contain an
      amino-terminal metalloprotease domain followed by a disintegrin domain, a
      cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin
      domain of metargidin contains an RGD tripeptide sequence, suggesting that it may
      potentially interact with the integrin family of proteins. Here we identify
      integrin ligands for metargidin on haemopoietic cells, by using a chimeric
      protein containing the extracellular domain of metargidin fused to the Fc portion
      of human IgG. Binding activity to a panel of human cell lines was analysed by
      solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line,
      U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent
      cation- and temperature- dependent and strongly enhanced by Mn2+, all features of
      integrin-mediated binding. Using a panel of anti-integrin antibodies we show that
      alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4
      cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was
      mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited
      cell binding to both cell lines. The specificity of the interaction between both
      alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase
      adhesion assays using purified recombinant integrins. These results together
      indicate that metargidin can function as a cell adhesion molecule via
      interactions with alphavbeta3 and alpha5beta1 integrins.

PMID- 9914171
TI  - Spermatogonial stem cells.
AB  - The mammalian seminiferous epithelium consists of a highly complex yet well
      organized cell population, with germ cells in mitosis and meiosis and postmeiotic
      cells undergoing transformation to become spermatozoa. To study the factors which
      control renewal and differentiation of spermatogonial stem cells, animal models
      are now available which allow for arrest and restart of spermatogonial
      differentiation. In addition, marked progress has been made in understanding the
      control of apoptosis and its role in spermatogonia. For the future,
      spermatogonial stem cell transplantation may have important practical
      applications.

PMID- 9914172
TI  - Notes from some crypt watchers: regulation of renewal in the mouse intestinal
      epithelium.
AB  - The mouse intestinal epithelium undergoes rapid renewal throughout life, thereby
      requiring continuous coordination of its cellular proliferation, differentiation,
      and death programs. Recent advances in our understanding of this process have
      highlighted some of the molecules that regulate renewal and their potential roles
      in gut neoplasia.

PMID- 9914173
TI  - Sister chromatid cohesion in mitosis.
AB  - Sister chromatid cohesion is essential for accurate chromosome segregation during
      the cell cycle. Newly identified structural proteins are required for sister
      chromatid cohesion and there may be a link in some organisms between the
      processes of cohesion and condensation. Proteins that induce and regulate the
      separation of sister chromatids have also been recently identified.

PMID- 9914175
TI  - Polo-like kinases: positive regulators of cell division from start to finish.
AB  - Present in organisms ranging from yeast to man, homologues of the Drosophila Polo
      kinase control multiple stages of cell division. At the onset of mitosis, Polo
      like kinases (Plks) function in centrosome maturation and bipolar spindle
      formation, and they contribute to the activation of cyclin-dependent kinase
      (Cdk)1-cyclin B. Subsequently, they are required for the inactivation of Cdk1 and
      exit from mitosis. In the absence of Plk function, mitotic cyclins fail to be
      destroyed, indicating that Plks are important regulators of the anaphase
      promoting complex/cyclosome (APC/C), a key component of the ubiquitin-dependent
      proteolytic degradation pathway. Finally, recent evidence implicates Plks in the
      temporal and spatial coordination of cytokinesis.

PMID- 9914176
TI  - Role of cytokines and extracellular matrix in the regulation of haemopoietic stem
      cells.
AB  - The understanding of molecular mechanisms regulating the formation, growth and
      differentiation of haemopoietic stem cells has advanced considerably recently.
      Particular progress has been made in defining the cytokines, chemokines and
      extracellular matrix components which retain and maintain primitive haemopoietic
      cell populations in bone marrow. Furthermore, signal transduction pathways that
      are critical for haemopoiesis, both in vivo and in vitro, and that are activated
      by cytokines have also been identified and further characterised. The importance
      of these processes has, this year, been exemplified by the phenotypes of mice
      deficient in key signal transduction proteins and the discovery that mutations in
      the component proteins of some signalling pathways are linked to human diseases.
      Significant advances in understanding the molecular mechanisms for mobilisation
      of stem cells from bone marrow have also been made this year; this has potential
      importance for bone marrow transplantation.

PMID- 9914174
TI  - Mitotic DNA damage and replication checkpoints in yeast.
AB  - Studies of the genetics of G2/M checkpoints in budding and fission yeasts have
      produced many of the defining concepts of checkpoint biology. Recent progress in
      the biochemistry of the checkpoint gene products is adding a mechanistic
      understanding to our models and identifying the components of the normal cell
      cycle machinery that are targeted by checkpoints.

PMID- 9914177
TI  - Recent progress in identifying genes regulating hematopoietic stem cell function
      and fate.
AB  - Significant advances in the use of genetic and molecular biology strategies have
      recently begun to identify genes that have a major impact on the determination,
      commitment and developmental potential of hematopoietic stem cells. Using a
      variety of experimental strategies, genes such as SCL, GATA-2, HoxB4, Flk-2, c
      mpl, dlk, and others have been implicated as important regulators of stem cell
      growth. In addition, genetic mapping has identified several loci that correlate
      strongly with stem cell numbers and proliferation.

PMID- 9914179
TI  - Negative control elements of the cell cycle in human tumors.
AB  - The retinoblastoma protein and p53 are both cell-cycle regulators and are,
      directly or indirectly, inactivated in the majority of human tumors. Recent
      studies have provided new mechanistic insights into how these proteins regulate
      cell growth in response to various intracellular and extracellular signals.

PMID- 9914178
TI  - Liver stem cells: a two compartment system.
AB  - Hepatocytes and biliary epithelia are phenotypically very dissimilar, but share a
      common ancestry. Hepatocytes regenerate very efficiently, and their division
      potential indicates that many of them are functional stem cells. When hepatocyte
      damaging agents also impair the regenerative ability of surviving hepatocytes, a
      potential stem cell system of biliary origin is activated to generate new
      hepatocytes - a reversal of ontogeny. Now both bile duct derived cells and
      hepatocytes can be isolated from the liver, genetically modified in vitro and
      returned to their in vivo origins where, after considerable population expansion,
      they can function as hepatocytes - paving the way for ex vivo gene therapy.

PMID- 9914180
TI  - SCF and APC: the Yin and Yang of cell cycle regulated proteolysis.
AB  - Progression through the cell cycle requires the activity of two ubiquitination
      complexes, the Skp1-cullin-F-box-protein complex (SCF) and the anaphase-promoting
      complex/cyclosome (APC). Observations in the past year have revealed unexpected
      similarities between the SCF and the APC and have allowed detailed insight into
      the regulation of their activities. Both complexes are now known to exist in
      different forms that target different substrates for ubiquitin-dependent
      proteolysis.

PMID- 9914181
TI  - The self-renewing mechanism of stem cells in the germline.
AB  - Germline stem cells (GSCs) are a self-renewing population of germ cells that
      serve as the source of gametes in diverse organisms. Current research suggests
      that the self-renewing division of GSCs is controlled both by somatic signaling
      and by intracellular mechanisms such as differential gene expression, asymmetric
      cytoskeletal organization, and the cell cycle machinery. These findings provide a
      framework for the further study of GSCs and stem cell renewal in general.

PMID- 9914182
TI  - Emerging mechanisms of eukaryotic DNA replication initiation.
AB  - Recent research has focused on proteins important for early steps in replication
      in eukaryotes, and particularly on Cdc6/Cdc18, the MCMs, and Cdc45. Although it
      is still unclear exactly what role these proteins play, it is possible that they
      are analogous to initiation proteins in prokaryotes. One specific model is that
      MCMs form a hexameric helicase at replication forks, and Cdc6/Cdc18 acts as a
      'clamp-loader' required to lock the MCMs around DNA. The MCMs appear to be the
      target of Cdc7-Dbf4 kinase acting at individual replication origins. Finally,
      Cdc45 interacts with MCMs and may shed light on how cyclin-dependent kinases
      activate DNA replication.

PMID- 9914183
TI  - Plasticity and stem cells in the vertebrate nervous system.
AB  - How and when do vertebrate neural precursor cells choose their fates? While some
      studies suggest a series of commitments on the road to fate choice, many recent
      experiments indicate that precursor fate choices can often be changed.
      Additionally, the identification of common gene control mechanisms in precursors
      suggest that these cells share fundamental properties throughout development.

PMID- 9914184
TI  - Cellular differentiation in the leaf.
AB  - The past year has seen significant advances in our understanding of the
      mechanisms that regulate cellular differentiation in the leaf. It has been
      suggested that a common developmental pathway involving MYB-like transcription
      factors is responsible for distinguishing between cellular identities in the
      epidermis and that nuclear-cytoplasmic partitioning of the GLABRA2 homeodomain
      protein plays a role in determining trichome cell fate. With respect to the
      differentiation of subepidermal cell types, molecular links have been made
      between auxin physiology and vascular development, and between plastid function
      and photosynthetic cell type development.

PMID- 9914185
TI  - Mechanisms of DNA bending.
AB  - Genome packaging and gene regulation require DNA bending. Recent developments in
      the elucidation of the mechanisms involved in DNA bending include new X-ray
      structures (most notably that of the mammalian nucleosome) wherein DNA is bent,
      controversy surrounding interpretation of DNA-bending experiments with basic
      leucine zipper proteins, studies of electrostatic effects in DNA bending, and the
      design of artificial DNA-bending ligands.

PMID- 9914186
TI  - Novel cofactor derivatives and cofactor-based models.
AB  - In 1997 and the first half of 1998, numerous publications appeared reporting
      studies of cofactors and their analogues in classical model systems and in enzyme
      catalyzed reactions directed at understanding the enzymatic reactions of their
      natural cofactors. Model systems based on flavins have provided new insights into
      enzymatic modulation of the flavin reduction potential, and enzymatic reactions
      of coenzyme A analogues and derivatives have been employed in several studies of
      coenzyme A utilizing enzymes. Coenzyme B12 analogues have been utilized as
      alternate cofactors for B12-utilizing enzymes, while pyrroloquinoline quinone
      esters and analogues have been employed in model studies of the reactions of
      quinoprotein-catalyzed reactions.

PMID- 9914187
TI  - Minimal model systems for beta sheet secondary structure in proteins.
AB  - Use of model systems to explore the forces that control beta sheet formation was
      stymied for many years by the perception that small increments of beta sheet
      necessarily aggregate. Recently, however, a number of short peptides (9-16
      residues in length) that fold into two-stranded antiparallel beta sheets ('beta
      hairpins') have been reported; several short peptides (20-24 residues in length)
      that fold into three-stranded antiparallel beta sheets have also been described.
      These model systems are beginning to provide fundamental insights into the
      origins of beta sheet conformational stability.

PMID- 9914188
TI  - DNA enzymes.
AB  - The past year has seen a coming-of-age in DNA enzyme research. Far from being
      laboratory curiosities, the activities of new DNA enzymes have broadened the
      known catalytic repertoire of nucleic acid enzymes, provided valuable insights
      into different mechanistic possibilities open to nucleic acid catalysts, and
      explored the importance for catalysis of native functionalities within DNA and
      RNA, as well as of a diversity of extrinsic cofactors. Thus, the first amino acid
      cofactor-utilizing DNA enzyme has been described, as well as DNA enzymes that
      cleave RNA without the assistance of any external cofactor. On the practical
      side, the most efficient RNA-cleaving nucleic acid enzyme described to date is a
      DNA enzyme.

PMID- 9914189
TI  - Progress towards synthetic enzymes for phosphoester hydrolysis.
AB  - Synthesis of artificial enzymes for catalyzing phosphoester hydrolysis has been
      attracting interest for a long time. The remarkable discovery that lanthanide
      ions catalyze the hydrolysis of DNA and RNA spurred the trend. Currently,
      progress is being made, mainly in the preparation of homogeneous catalysts, the
      promotion of catalytic activity by using acid/base cooperation within catalysts,
      the detailed understanding of the reaction mechanisms involved, and the design of
      artificial enzymes expressing high specificity and catalytic turn-over.

PMID- 9914190
TI  - Oligosaccharide receptors for bacteria: a view to a kill.
AB  - Oligosaccharide recognition is a major means of bacterial-host cell attachment.
      Bacterial-host receptor binding can subvert host signaling pathways to cause
      pathology. In addition, pathogenic bacteria can utilize more than one recognition
      system to bind host cells. Recent studies of Helicobacter pylori illustrate both
      these points. Together with this redundancy in recognition, the importance of
      multivalent sugar binding has become apparent. Multivalent sugar receptor analogs
      have been used to both prevent and detach adherent bacteria. Several new chemical
      technologies for the generation of bioactive glycopolymers have been developed
      and may be successfully adapted to address both these issues.

PMID- 9914191
TI  - Solid-phase oligosaccharide synthesis and related technologies.
AB  - Research efforts directed at the development of methodologies effective for solid
      phase synthesis of oligosaccharides have resulted in a number of impressive
      achievements. In addition, closely related technologies, such as soluble polymer
      supported synthesis and fluorous synthesis of the same class of molecules, have
      proved to be quite promising.

PMID- 9914192
TI  - Hydrophobic core packing and protein design.
AB  - Over the past few years, we have witnessed exciting advances in protein design.
      Several groups have reported success in the design of hydrophobic cores, and the
      principles developed in these studies have been recently applied to the full
      sequence design of a small protein motif and the design of a catalytically active
      metal center. These successes suggest that designing large, functional proteins
      in computero is more feasible than ever before.

PMID- 9914193
TI  - Applications of dendrimers in bio-organic chemistry.
AB  - Dendrimers represent a new class of highly branched polymers whose interior
      cavities and multiple peripheral groups facilitate potential applications in
      biomedicine and bio-organic chemistry. Major advances in the past year were made
      in the synthesis and study of new carbohydrate, nucleic acid, and peptide
      dendrimers, as well as in the use of dendrimers as magnetic resonance imaging
      contrast agents, as agents for cellular delivery of nucleic acids, and as
      scaffolds for biomimetic systems.

PMID- 9914194
TI  - Chemistry and physics of giant vesicles as biomembrane models.
AB  - The giant vesicle is becoming an object of intense scrutiny by chemists,
      biologists, and physicists who are interested in membrane behavior. Recent
      advances include new models to explain morphological changes, new experimental
      methods for studying vesicle adhesion, layering and adsorption, and new
      cataloging of 'cytomimetic' processes.

PMID- 9914195
TI  - Carriers and channels: current progress and future prospects.
AB  - Recent advances in the understanding of biological transport and in the design of
      artificial transport systems have resulted from the structural elucidation of the
      K+ ion channel and from synthesis of artificial receptors for cations and anions,
      as well as neutral and zwitterionic organic molecules. Sensors, gated carriers,
      and self-assembling capsules and nanotubes are all important offsprings of
      current efforts to mimic natural transport across biomembranes.

PMID- 9914197
TI  - Biopolymers 

PMID- 9914196
TI  - Theozymes and compuzymes: theoretical models for biological catalysis.
AB  - A theozyme is a theoretical enzyme constructed by computing the optimal geometry
      for transition-state stabilization by functional groups. It is created in order
      to permit quantitative assessment of catalytic function. Theozymes have been used
      to elucidate the role of transition-state stabilization in the mechanisms
      underlying enzyme- and antibody-catalyzed hydroxyepoxide cyclizations,
      eliminations and decarboxylations, peptide and ester hydrolyses, and pericyclic
      and radical reactions. The enzymes studied include orotodine monophosphate
      decarboxylase, HIV protease and ribonucleotide reductase.

PMID- 9914198
TI  - Model systems 

PMID- 9914199
TI  - Plastid evolution: origins, diversity, trends.
AB  - The amazing diversity of extant photosynthetic eukaryotes is largely a result of
      the presence of formerly free-living photosynthesizing organisms that have been
      sequestered by eukaryotic hosts and established as plastids in a process known as
      endosymbiosis. The evolutionary history of these endosymbiotic events was
      traditionally investigated by studying ultrastructural features and pigment
      characteristics but in recent years has been approached using molecular sequence
      data and gene trees. Two important developments, more detailed studies of members
      of the Cyanobacteria (from which plastids ultimately derive) and the availability
      of complete plastid genome sequences from a wide variety of plant and algal
      lineages, have allowed a more accurate reconstruction of plastid evolution.

PMID- 9914200
TI  - Evolutionary anomalies among the aminoacyl-tRNA synthetases.
AB  - Unexpected relationships among the various aminoacyl-tRNA synthetases continue to
      be uncovered. The question arises - is this mainly the result of promiscuous
      exchange, or is the confusion really a reflection of the differential loss of
      past duplications? Phylogenetic analysis may yet provide the answer.

PMID- 9914201
TI  - Do we understand the evolution of genomic imprinting?
AB  - The conflict theory is the only hypothesis to have attracted any critical
      attention for the evolution of genomic imprinting. Although the earliest data
      appeared supportive, recent systematic analyses have not confirmed the model's
      predictions. The status of theory remains undecided, however, as post-hoc
      explanations can be provided as to why these predictions are not borne out.

PMID- 9914202
TI  - The evolution of the Hox cluster: insights from outgroups.
AB  - Two burgeoning research trends are helping to reconstruct the evolution of the
      Hox cluster with greater detail and clarity. First, Hox genes are being studied
      in a broader phylogenetic sampling of taxa: the past year has witnessed important
      new data from teleost fishes, onychophorans, myriapods, polychaetes,
      glossiphoniid leeches, ribbon worms, and sea anemones. Second, commonly accepted
      notions of animal relationships are being challenged by alternative phylogenetic
      hypotheses that are causing us to rethink the evolutionary relationships of
      important metazoan lineages, especially arthropods, annelids, nematodes, and
      platyhelminthes.

PMID- 9914203
TI  - Metazoan phylogenies: falling into place or falling to pieces? A palaeontological
      perspective.
AB  - Metazoan phylogeny is in a state of ferment, stirred by the addition of new
      molecular trees as well as controversial interpretations of molecular 'clocks'.
      Concerning the latter topic, the clocks recurrently point to divergence times
      substantially older than the known fossil record. Some attempt reconciliation by
      appealing to a conveniently cryptic interval prior to the first fossils. This
      effectively reduces the fossil record to an erratic search-light giving only
      glimpses into the true evolutionary history. Other options, however, remain open.
      Molecular clocks may themselves run erratically and what happens in molecular
      history may not coincide with the emergence of body plans.

PMID- 9914204
TI  - Everything in moderation: archaea as 'non-extremophiles'.
AB  - Well characterized and cultivated archaea are prokaryotic specialists that thrive
      in habitats of elevated temperature, low pH, high salinity, or strict anoxia.
      Recently, however, new groups of abundant, uncultivated archaea have been found
      to be widespread in more pedestrian biotopes, including marine plankton,
      terrestrial soils, lakes, marine and freshwater sediments, and in association
      with metazoa. Research efforts are presently focused on characterizing the
      physiology, biochemistry and genetics of these abundant and cosmopolitan but
      poorly understood archaea.

PMID- 9914205
TI  - When is homology not homology?
AB  - Although genes have specific phenotypic consequences in a given species, this
      functional relationship can clearly change during the course of evolution. Many
      cases of evolutionary dissociations between homologous genes and homologous
      morphological features are now known. These dissociations have interesting and
      important implications for understanding the genetic basis for evolutionary
      change in morphology.

PMID- 9914206
TI  - Eukaryote genome duplication - where's the evidence?
AB  - Several eukaryotes, including maize, yeast and Xenopus, are degenerate polyploids
      formed by relatively recent whole-genome duplications. Ohno's conjecture that
      more ancient genome duplications occurred in an ancestor of vertebrates is
      probably at least partly true but the present shortage of gene sequence and map
      information from vertebrates makes it difficult to either prove or disprove this
      hypothesis. Candidate paralogous segments in mammalian genomes have been
      identified but the lack of statistical rigour means that many of the proposals in
      the literature are probably artefacts.

PMID- 9914207
TI  - Early branching eukaryotes?
AB  - Recent phylogenetic analyses suggest that Giardia, Trichomonas and Microsporidia
      contain genes of mitochondrial origin and are thus unlikely to be primitively
      amitochondriate as previously thought. Furthermore, phylogenetic analyses of
      multiple data sets suggest that Microsporidia are related to Fungi rather than
      being deep branching as depicted in trees based upon SSUrRNA analyses. There is
      also room for doubt, on the basis of a lack of consistent support from analyses
      of other genes, whether Giardia or Trichomonas branch before other eukaryotes.
      So, at present, we cannot be sure which eukaryotes are descendants of the
      earliest-branching organisms in the eukaryote tree. Future resolution of the
      order of emergence of eukaryotes will depend upon a more critical phylogenetic
      analysis of new and existing data than hitherto. Hypotheses of branching order
      should preferably be based upon congruence between independent data sets, rather
      than on single gene trees.

PMID- 9914208
TI  - How good are deep phylogenetic trees?
AB  - Great interest is given to species emerging early in phylogenetic reconstruction
      because they are often assumed to represent an ancestor. Recent studies indicate,
      however, that species branching deep in molecular trees are often fast-evolving
      ones, misplaced because of the long-branch artefact. The detection of genuinely
      deep-branching organisms remains an elusive task.

PMID- 9914209
TI  - Evolution of the diverse antifreeze proteins.
AB  - Different types of ice-growth-inhibiting antifreeze proteins, first recognized in
      fish, have now been isolated from insects and plants, and the list continues to
      expand. Their structures are amazingly diverse; how they attain the same function
      are subjects of intense research. Evolutionary precursors of several members have
      been identified - divergent proteins of apparently unrelated function. The
      hybridization of information from structural and molecular evolution studies of
      these molecules provides a forum in which issues of selection, gene genealogy,
      adaptive evolution, and invention of a novel function can be coherently
      addressed.

PMID- 9914210
TI  - The recent origins of spliceosomal introns revisited.
AB  - Does the intron/exon structure of eukaryotic genes belie their ancient assembly
      by exon-shuffling or have introns been inserted into preformed genes during
      eukaryotic evolution? These are the central questions in the ongoing 'introns
      early' versus 'introns-late' controversy. The phylogenetic distribution of
      spliceosomal introns continues to strongly favor the intronslate theory. The
      introns-early theory, however, has claimed support from intron phase and protein
      structure correlations.

PMID- 9914211
TI  - Translational selection and molecular evolution.
AB  - An interplay among experimental studies of protein synthesis, evolutionary
      theory, and comparisons of DNA sequence data has shed light on the roles of
      natural selection and genetic drift in 'silent' DNA evolution.

PMID- 9914212
TI  - Reproductive isolation in Drosophila: how close are we to untangling the genetics
      of speciation?
AB  - Our understanding of the genetic basis of reproductive isolation in Drosophila
      has progressed rapidly over the past decade. Details of the genetic structure of
      hybrid sterility have been revealed and a general consensus has been reached
      concerning the genetic bases of Haldane's rule. Genetic analyses now reach beyond
      hybrid sterility and inviability, allowing us to make important comparisons
      across different traits involved in reproductive isolation. Expansion of genetic
      studies to include rescue of hybrid incompatibilities has opened the door for
      more detailed molecular and developmental analyses of reproductive isolation than
      has ever before been possible.

PMID- 9914213
TI  - Big trees from little genomes: mitochondrial gene order as a phylogenetic tool.
AB  - Gene arrangement comparisons are a powerful tool for phylogenetic studies,
      especially those focused on ancient relationships. Recent reports using metazoan
      mitochondrial genomes address evolutionary relationships as well as rates and
      mechanisms of rearrangement. Mitochondrial systems serve as a model for larger
      scale comparisons of whole organismal genomes and a stimulus for developing
      methods for reconstructing the patterns of rearrangement.

PMID- 9914214
TI  - Control of immune pathology by regulatory T cells.
AB  - There is now compelling evidence that immune responses for both foreign and self
      antigens are downregulated by T cells that are specialised for this function;
      these are known as regulatory T (T reg) cells. This review describes progress in
      the characterisation of the T reg cells that mediate both mucosal tolerance and
      tolerance to self antigens. The recent work on the antigen specificity,
      generation and mode of action of T reg cells is also reviewed.

PMID- 9914215
TI  - T cell immunity to oral allergens.
AB  - Considerable light has been thrown on the mechanisms of oral tolerance (or, more
      correctly, orally-induced systemic tolerance) in the past 12-18 months. While it
      is very clear that T cell anergy and apoptosis can occur after being fed antigen,
      a major pathway that has been described in different models is the induction of
      regulatory T cells which secrete transforming growth factor beta. These cells
      have been designated Th3 cells but their relation to the in-vitro-generated Tr
      cells, which inhibit tissue-damaging T cell responses in the gut mucosa, is not
      known. An important discovery is that food antigens have major systemic effects
      on T cells, similar in many ways to those seen following intravenous injection of
      soluble antigens. This conceptually moves us away from the notion that there is
      something special about mucosal (compared to systemic) lymphoid tissue to the
      notion that it is the type of antigens seen in the gut (i.e. digested, soluble
      polypeptides) which dictates the types of response seen there. After initial
      excitement, clinical trials using oral tolerance to treat autoimmune disease have
      been somewhat disappointing.

PMID- 9914216
TI  - Genetic susceptibility factors in type 1 diabetes: linkage, disequilibrium and
      functional analyses.
AB  - Continuing progress has been made in elucidating the genetic factors involved in
      type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year.
      Two genome scans suggested additional susceptibility intervals and provided
      supporting evidence for several previously reported linkages. Other studies
      focused on the confirmation of linkage using multipoint sibpair analyses with
      densely spaced markers and multiethnic collections of families. Although
      significant and consistent linkage evidence was reported for the susceptibility
      intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25),
      evidence for most other intervals varies in different data sets -probably due to
      a weak effect of the disease genes, genetic heterogeneity or random variation.
      Linkage disequilibrium mapping has become an increasingly important tool for both
      the confirmation and fine-mapping of susceptibility intervals, as well as
      identification of etiological mutations. Functional studies indicate, firstly,
      that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind
      and present nonoverlapping peptides and, secondly, that the variable number of
      tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2)
      regulates insulin expression in the thymus.

PMID- 9914217
TI  - Genetics of susceptibility to chronic experimental encephalomyelitis and
      arthritis.
AB  - The recent developments in genetic techniques and the development of more
      appropriate animal models for rheumatoid arthritis and multiple sclerosis make it
      possible to use a new approach for understanding these complex diseases. Thus it
      is now meaningful to address the question of which genes are causing the
      diseases. Several new associations with loci outside the MHC region have now been
      identified in models for both rheumatoid arthritis and multiple sclerosis. Some
      of these are shared between diseases - for example loci on mouse chromosome 3
      (experimental allergic encephalomyelitis, collagen-induced arthritis and
      Theiler's encephalomyelitis) and rat chromosome 4 (collagen-induced arthritis and
      the experimental allergic encephalomyelitis induced by myelin oligodendrocytic
      glycoprotein).

PMID- 9914218
TI  - The role of antigen-presenting cells in the regulation of allergen-specific T
      cell responses.
AB  - Allergic reactions in atopic patients follow from a generalized enhanced
      polarization of Th cells, predominantly imposed by factors derived from antigen
      presenting cells from a pathogen-stressed tissue; these sample information not
      only on antigen structures but also on the nature of the stress. Antigen
      presenting cells of atopic individuals show aberrant characteristics which,
      through a highly interactive communication network, play an active role in
      aberrant Th-cell polarization. This generalized bias may follow from intrinsic
      abnormalities of antigen-presenting cells and also from a low degree of cross
      regulation by micro-organisms.

PMID- 9914219
TI  - Regulation of autoimmunity by proinflammatory cytokines.
AB  - Studies extending over a decade have provided compelling evidence to suggest that
      chronic expression of proinflammatory cytokines in vivo leads to unique
      regulatory properties that target the cognate immune response in a way that
      appears to be beneficial to the host. This review focuses on the prototypic
      proinflammatory cytokine tumour necrosis factor alpha, because recent studies of
      autoimmune disease in mice and man have unraveled a novel and unexpected
      immunosuppressive role for this inflammatory mediator during the effector phase
      of the autoimmune process. So far, T lymphocytes would appear to be important
      cellular targets of this immunoregulatory effect.

PMID- 9914220
TI  - Genetics of autoimmune diabetes in animal models.
AB  - Type I diabetes has resisted direct genetic analysis in humans but two excellent
      models of disease in rodents provide a more readily manipulated alternative for
      study. These rodent models are being used successfully to localize the genes that
      are involved in disease pathogenesis in preparation for positional cloning. In
      addition, mice carrying transgenes and null mutations related to T cell function
      have been used to demonstrate potential mechanisms for both MHC-dependence and
      specific effector functions, such as cytokine release and cytotoxicity.

PMID- 9914221
TI  - Indoor versus outdoor allergens in allergic respiratory disease.
AB  - Immediate hypersensitivity to indoor or outdoor allergens is strongly associated
      with asthma or hay fever, respectively. Recent progress has defined the
      sequences, tertiary structures and enzymatic functions of many of the proteins
      involved; furthermore, the immune responses to these proteins have been examined;
      however, the mechanisms responsible for the dichotomous response remain elusive.
      The resolution of such mechanisms may explain the large increase in the
      prevalence of eosinophil-rich inflammation of the lower respiratory tract.

PMID- 9914222
TI  - Immunotherapy of allergy: anergy, deletion, and immune deviation.
AB  - Decreased allergen-specific T cell proliferation and dysregulated cytokine
      synthesis accompany allergen immunotherapy, consistent with mechanisms of anergy
      and immune deviation. Recent studies emphasise the pivotal role of decreased T
      cell IL-4:IFN-gamma ratios. A landmark clinical trial of T cell epitope peptides
      for venom-immunotherapy shows efficacy and safety; murine models suggest
      intramolecular epitope-suppression inhibits responses to the whole allergen.

PMID- 9914223
TI  - Susceptibility to lupus nephritis in the NZB/W model system.
AB  - Advances in genetic mapping have resulted in the identification of multiple lupus
      susceptibility loci in the NZB/W mouse model. The analysis of congenic strains
      carrying these loci is now providing functional data on their role in lupus
      pathogenesis and is paving the way to the identification of the susceptibility
      genes and their molecular characterization.

PMID- 9914224
TI  - Peripheral-antigen-expressing cells in thymic medulla: factors in self-tolerance
      and autoimmunity.
AB  - The thymus expresses many genes previously thought to be specific for cell types
      in other organs. Thus, insulin genes are expressed in rare cells of the thymic
      medulla. Thymus transplantation demonstrates a functional capability of such
      expression for self-tolerance induction. Correlative studies suggest that
      impaired thymic expression confers susceptibility to autoimmune disease.

PMID- 9914225
TI  - Langerhans cells and chemical allergy.
AB  - Epidermal Langerhans cells (LCs) play a pivotal role in the induction of
      cutaneous immune responses, including those provoked by chemical allergens. The
      delivery by LCs of allergen to draining lymph nodes requires cell migration from
      the skin, a process that is dependent upon the availability of epidermal
      cytokines -particularly TNF-alpha and IL-1beta. Here we consider the ways in
      which these cytokines interact with LCs to both induce and regulate their
      mobilization in response to skin sensitization. In addition, the effects of these
      cytokines on both the selectivity of LC migration from the skin and protection of
      LCs from cell death are considered. Finally, the possible counter-regulatory
      activity of other cutaneous cytokines and the influence of LCs on the development
      of selective T lymphocyte responses are explored.

PMID- 9914226
TI  - The genetics of human systemic lupus erythematosus.
AB  - Major advances in understanding the genetic foundation of systemic lupus
      erythematosus are in the offing. Genetic association studies suggest multiple
      effects that include those encoded by the HLA region, the genes for Fcgamma
      receptors and other genes such as that for the mannose-binding protein. Genome
      scan studies suggest many (at least twelve) genetic linkages with lupus.
      Identifying the genes linked with lupus is likely to require many years of
      concerted effort, as well as the availability and evaluation of much larger
      pedigree collections.

PMID- 9914227
TI  - Autoreactivity versus autoaggression: a different perspective on human
      autoantigens.
AB  - Antigen-specific B and T cell responses against myelin basic protein, as well as
      responses against beta-islet-cells or joint tissue, are commonly found both in
      patients with autoimmune disease and in normal control subjects with disease
      associated HLA-DR/DQ alleles. Thus, autoreactive immune responses are not disease
      specific; however, the presence of certain autoantibodies may have prognostic
      value and may aid in disease management.

PMID- 9914228
TI  - Inheritance of susceptibility to multiple sclerosis.
AB  - In recent years, epidemiological evidence supporting the genetic basis of
      multiple sclerosis has been extended and whole-genome linkage screening has
      advanced the mapping of the involved genes. Understanding of the known HLA
      associations has also improved and many candidate genes have been studied.

PMID- 9914230
TI  - Autoimmunity 

PMID- 9914229
TI  - The role of MHC class II molecules in susceptibility and resistance to
      autoimmunity.
AB  - The mechanism by which particular MHC class II alleles mediate susceptibility to
      a given autoimmune disease is unknown. During the past year, reports have
      indicated that the effects of MHC class II alleles which protect against type I
      diabetes in the nonobese diabetic mouse strain may, in some cases, be due to
      negative selection of diabetogenic T cell receptors and, in other cases, to
      positive selection of other T cells with a suppressive action on the diabetic
      process. Progress towards understanding the mechanisms of susceptibility
      continues to lag.

PMID- 9914231
TI  - CD8+ T cells in atopic disease.
AB  - In recent years there has been a tremendous expansion in our understanding about
      CD8(+) T cells. We now know that, as for CD4(+) T cells, they can be divided into
      subsets (Tc1 and Tc2) according to the cytokines they secrete. These subsets may
      differ in their capacity to kill and may even, in some cases, provide help for B
      cell antibody production or be involved in the induction of inflammatory
      responses. In addition, there is a host of cross-regulatory networks between
      different CD4(+) and CD8(+) subsets that control the magnitude and duration of
      immune responses. The observation that some antigens that are normally presented
      by MHC class II and seen by CD4(+) T cells can be presented by MHC class I and
      stimulate CD8(+) T cells increases the possibility for such interactions. During
      the next few years we can expect that our understanding of the biology of CD8(+)
      T cells and their role in immunity will increase.

PMID- 9914232
TI  - Functional role of plateau potentials in vertebrate motor neurons.
AB  - The expression of plateau potentials in spinal motor neurons is regulated by
      neuromodulatory substances. Recent experiments have shed new light on this
      regulation at the cellular level. It is now possible to evaluate the existence of
      plateau potentials in intact organisms, including humans, and to address the
      functional role of plateau potentials in motor control, as well as in information
      transfer in the brain.

PMID- 9914233
TI  - Biorobotic approaches to the study of motor systems.
AB  - Biorobotics is a promising new area of research at the interface between biology
      and robotics. Robots can either be used as physical models of biological systems
      or be directly inspired by biological studies. A great deal of progress has
      recently been made in biorobotic studies of locomotion, orientation, and
      vertebrate arm control.

PMID- 9914234
TI  - New developments in understanding the etiology of Parkinson's disease and in its
      treatment.
AB  - Important recent advances have been made in understanding the etiology and
      pathogenesis of Parkinson's disease, as well as in developing novel treatments.
      Two newly identified genes, alpha-synuclein and parkin, have been linked to
      parkinsonism. In addition, disturbances to the normal basal ganglia circuits in
      Parkinson's patients are being described at both anatomical and physiological
      levels. These developments provide a strong scientific basis for novel medical
      and surgical strategies to treat the profound motor disturbances in patients with
      Parkinson's disease.

PMID- 9914235
TI  - Intersegmental coordination in invertebrates and vertebrates.
AB  - How does the CNS coordinate muscle contractions between different body segments
      during normal locomotion? Work on several preparations has shown that this
      coordination relies on excitability gradients and on differences between
      ascending and descending intersegmental coupling. Abstract models involving
      chains of coupled oscillators have defined properties of coordinating circuits
      that would permit them to establish a constant intersegmental phase in the face
      of changing periods. Analyses that combine computational and experimental
      strategies have led to new insights into the cellular organization of
      intersegmental coordinating circuits and the neural control of swimming in
      lamprey, tadpole, crayfish and leech.

PMID- 9914237
TI  - Learning in the oculomotor system: from molecules to behavior.
AB  - A combination of system-level and cellular-molecular approaches is moving studies
      of oculomotor learning rapidly toward the goal of linking synaptic plasticity at
      specific sites in oculomotor circuits with changes in the signal-processing
      functions of those circuits, and, ultimately, with changes in eye movement
      behavior. Recent studies of saccadic adaptation illustrate how careful behavioral
      analysis can provide constraints on the neural loci of plasticity. Studies of
      vestibulo-ocular adaptation are beginning to examine the molecular pathways
      contributing to this form of cerebellum-dependent learning.

PMID- 9914236
TI  - Sensory pathways and their modulation in the control of locomotion.
AB  - Recent experiments have extended our understanding of how sensory information in
      premotor networks controlling motor output is processed during locomotion, and at
      what level the efficacy of specific sensory-motor pathways is determined. Phasic
      presynaptic inhibition of sensory transmission combined with postsynaptic
      alterations of excitatory and inhibitory synaptic transmission from interneurons
      of the premotor networks contribute to the modulation of reflex pathways and to
      the generation of reflex reversal. These mechanisms play an important role in
      adapting the operation of central networks to external demands and thus help
      optimize sensory-motor integration.

PMID- 9914238
TI  - Development of rhythmic pattern generators.
AB  - In contrast to the wealth of knowledge about the organizational rules of adult
      central pattern generators, far less is known about how these networks are
      assembled during development. The basic architecture for adult central pattern
      generators appears early in development but different generators may follow
      completely different developmental pathways to reach maturity. Recent evidence
      suggests that neuromodulatory inputs, in addition to their short-term adaptive
      control of central pattern generator activity, play a crucial role in both the
      final developmental tuning and the long-term maintenance of adult network
      function.

PMID- 9914239
TI  - Visuomotor transformations: early cortical mechanisms of reaching.
AB  - Recent studies of visually guided reaching in monkeys support the hypothesis that
      the visuomotor transformations underlying arm movements to spatial targets
      involve a parallel mechanism that simultaneously engages functionally related
      frontal and parietal areas linked by reciprocal cortico-cortical connections. The
      neurons in these areas possess similar combinations of response properties. The
      multimodal combinatorial properties of these neurons and the gradient
      architecture of the parietofrontal network emerge as a potential substrate to
      link the different sensory and motor signals that arise during reaching behavior
      into common hybrid reference frames. This convergent combinatorial process is
      evident at early stages of visual information processing in the occipito-parietal
      cortex, suggesting the existence of re-entrant motor influences on cortical areas
      once believed to have only visual functions.

PMID- 9914240
TI  - A role for the cerebellum in the control of limb movement velocity.
AB  - Accepting, rejecting or modifying the many different theories of the cerebellum's
      role in the control of movement requires an understanding of the signals encoded
      in the discharge of cerebellar neurons and how those signals are transformed by
      the cerebellar circuitry. Particularly challenging is understanding the sensory
      and motor signals carried by the two types of action potentials generated by
      cerebellar Purkinje cells, the simple spikes and complex spikes. Advances have
      been made in understanding this signal processing in the context of voluntary arm
      movements. Recent evidence suggests that mossy fiber afferents to the cerebellar
      cortex are a source of kinematic signals, providing information about movement
      direction and speed. In turn, the simple spike discharge of Purkinje cells
      integrates this mossy fiber information to generate a movement velocity signal.
      Complex spikes may signal errors in movement velocity. It is proposed that the
      cerebellum uses the signals carried by the simple and complex spike discharges to
      control movement velocity for both step and tracking arm movements.

PMID- 9914241
TI  - Modulation of vertebrate and invertebrate neuromuscular junctions.
AB  - Advances in our understanding of how the neuromuscular junction is modulated
      include an expanded appreciation of the many different types of modulatory
      influences, from soluble factors to second-messenger systems, to specific
      proteins in nerve and muscle. Recent studies indicate that modulation of
      neuromuscular function is effected on both the presynaptic and postsynaptic sides
      of the neuromuscular junction.

PMID- 9914242
TI  - Brainstem mechanisms underlying feeding behaviors.
AB  - The essential elements controlling trigeminal motoneurons during feeding lie
      between the trigeminal and facial motor nuclei. These include populations of
      neurons in the medial reticular formation and pre-motoneurons in the lateral
      brainstem that reorganize to generate various patterns. Orofacial sensory
      feedback, antidromic firing in spindle afferents and intrinsic properties of
      motoneurons also contribute to the final masticatory motor output.

PMID- 9914244
TI  - Cellular, synaptic, network, and modulatory mechanisms involved in rhythm
      generation.
AB  - The membrane properties and the synaptic interactions of individual neurons, as
      well as the interactions between neuronal networks, all contribute to the
      formation of the complex patterns of activity that underlie rhythmic motor
      patterns and slow-wave sleep rhythms. These properties and interactions are
      potential points of modulation for further refining network output. Recent work
      illustrates the range of these properties and interactions and suggests how they
      may be modulated.

PMID- 9914243
TI  - The genetic and molecular mechanisms of motor neuron disease.
AB  - Significant progress has been made in the identification of genes and chromosomal
      loci associated with several types of motor neuron disease. Of particular
      interest is recent work on the pathogenic mechanisms underlying these diseases,
      especially studies in in vitro model systems and in transgenic and gene-targeted
      mice.

PMID- 9914245
TI  - Regeneration in the spinal cord.
AB  - Important advances have been made in our understanding of conditions that
      influence the intrinsic capacity of mature CNS neurons to initiate and maintain a
      regrowth response. The combination of exogenous neurotrophic support with
      strategies to alter the terrain at the injury site itself suggests that there are
      important interactions between them that lead to increased axonal regeneration.
      The ability of chronically injured neurons to initiate a regeneration response is
      unexpected. Our view of the role that inhibitors play in restricting axonal
      growth has also expanded. The findings indicate that the windows of opportunity
      for enhancing growth after spinal cord injury may be more numerous than
      previously thought.

PMID- 9914246
TI  - Genetic and molecular analyses of motoneuron development.
AB  - Motoneurons have distinct identities and muscle targets. Recent classical and
      molecular genetic studies in flies and vertebrates have begun to elucidate how
      motoneuron identities and target specificities are established. Many of the same
      molecules participate in the guidance of both vertebrate and fly motor axons. It
      is less clear, however, whether the same molecular mechanisms establish
      vertebrate and fly motoneuron identities.

PMID- 9914247
TI  - Carbamoyl phosphate synthetase: a tunnel runs through it.
AB  - The direct transfer of metabolites from one protein to another in a biochemical
      pathway or between one active site and another within a single enzyme has been
      described as substrate channeling. The first structural visualization of such a
      phenomenon was provided by the X-ray crystallographic analysis of tryptophan
      synthase, in which a tunnel of approximately 25 A in length was observed. The
      recently determined three-dimensional structure of carbamoyl phosphate synthetase
      sets a new long distance record in that the three active sites are separated by
      nearly 100 A.

PMID- 9914248
TI  - Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
AB  - Recent studies of glutamine PRPP amidotransferase have provided a new
      understanding of the function and mechanism of this rather complicated enzyme
      that may be a paradigm for other complex enzymes. New insights have been gained
      into the mechanisms of catalysis in the active sites of the two half-reactions,
      catalytic coupling, allosteric control by feedback inhibitors and the channeling
      of reaction and metabolic intermediates.

PMID- 9914249
TI  - The structure, catalytic mechanism and regulation of adenylyl cyclase.
AB  - The recent structure determinations of the mammalian effector enzyme adenylyl
      cyclase reveal the structure of its catalytic core, provide new insights into its
      catalytic mechanism and suggest how diverse signaling molecules regulate its
      activity.

PMID- 9914250
TI  - Managing and manipulating carbocations in biology: terpenoid cyclase structure
      and mechanism.
AB  - Terpenoid cyclases catalyze remarkably complex cyclization cascades that are
      initiated by the formation of a highly reactive carbocation in a polyisoprene
      substrate. Recent crystal structures of terpenoid cyclases show how these enzymes
      provide a template for binding and stabilizing the flexible substrate in the
      precise orientation required for catalysis, trigger carbocation formation,
      chaperone the conformations of the reactive carbocation intermediates through a
      unique cyclization sequence, and sequester and stabilize carbocations from
      premature quenching. Notably, terpenoid cyclases and catalytic antibodies have
      converged to similar chemical and structural strategies for managing highly
      reactive carbocations in polyisoprene cyclization cascades.

PMID- 9914251
TI  - The mechanism of action of T7 DNA polymerase.
AB  - The recent crystal structure determination of T7 DNA polymerase complexed to a
      deoxynucleoside triphosphate and primer-template DNA has provided the first
      glimpse of a replicative DNA polymerase in a catalytic complex. The structure
      complements many functional and structural studies of this and other DNA
      polymerases, allowing a detailed evaluation of proposals for the mechanism of
      nucleotidyl transfer and the exploration of the basis for the high fidelity of
      template-directed DNA synthesis.

PMID- 9914252
TI  - RNA catalysis.
AB  - Our understanding of the relationship between the structure of RNA and its
      catalytic activity has advanced significantly in the past year. These advances
      include time-resolved crystallographic studies on the hammerhead ribozyme, as
      well as new structures of a group I intron, a lead(II)-cleavage ribozyme, a
      hepatitis delta virus ribozyme, and components of the spliceosome machinery and
      the peptidyl transferase center of the ribosome and, most significantly, the
      structure of the ribosome itself.

PMID- 9914253
TI  - Three-dimensional structural studies on fragments of fibrinogen and fibrin.
AB  - Fibrinogen is a 340 kDa glycoprotein found in the blood plasma of all
      vertebrates. It is transformed into a fibrin clot by the action of thrombin.
      Recent X-ray structures of core fragments of both fibrinogen and fibrin have
      revealed many details about this polymerization event. These include structures
      of a 30 kDa recombinant gammaC domain, an 86 kDa fragment D from human fibrinogen
      and a cross-linked double-D fragment from fibrin.

PMID- 9914254
TI  - Messages from ultrahigh resolution crystal structures.
AB  - The ever growing availability of macromolecular crystal structures determined at
      atomic resolution has now reached a critical size, making it possible to obtain
      statistically unbiased data on both protein stereochemistry and the validity of
      the parameters used in their refinement. Besides the determination of the precise
      geometry of proteins and their active sites, high resolution structures have made
      it possible to check the application of normal mode calculations, to calculate
      charge density distributions and to analyze hydration shells around protein
      molecules. Even if only a few structures involve protein complexes, either with
      ligands or prosthetic groups, the information obtained in these cases is of great
      interest for obtaining the physical parameters of these interactions.

PMID- 9914255
TI  - Active sites of transition-metal enzymes with a focus on nickel.
AB  - Since 1995, crystal structures have been determined for many transition-metal
      enzymes, in particular those containing the rarely used transition metals
      vanadium, molybdenum, tungsten, manganese, cobalt and nickel. Accordingly, our
      understanding of how an enzyme uses the unique properties of a specific
      transition metal has been substantially increased in the past few years. The
      different functions of nickel in catalysis are highlighted by describing the
      active sites of six nickel enzymes - methyl-coenyzme M reductase, urease,
      hydrogenase, superoxide dismutase, carbon monoxide dehydrogenase and acetyl
      coenzyme A synthase.

PMID- 9914256
TI  - The stability of proteins in extreme environments.
AB  - Three complete genome sequences of thermophilic bacteria provide a wealth of
      information challenging current ideas concerning phylogeny and evolution, as well
      as the determinants of protein stability. Considering known protein structures
      from extremophiles, it becomes clear that no general conclusions can be drawn
      regarding adaptive mechanisms to extremes of physical conditions. Proteins are
      individuals that accumulate increments of stabilization; in thermophiles these
      come from charge clusters, networks of hydrogen bonds, optimization of packing
      and hydrophobic interactions, each in its own way. Recent examples indicate ways
      for the rational design of ultrastable proteins.

PMID- 9914257
TI  - The adenylyl and guanylyl cyclase superfamily.
AB  - New structures solved in 1997 revealed that the adenylyl cyclase core consists of
      a pair of catalytic domains arranged in a wreath. Homologous catalytic domains
      are arranged in diverse adenylyl and guanylyl cyclases as symmetric homodimers or
      pseudosymmetric heterodimers. The kinship of the adenylyl and guanylyl cyclases
      has been confirmed by the structure-based interconversion of their nucleotide
      specificities. Catalysis is activated when two metal-binding aspartate residues
      on one domain are juxtaposed with a key aspargine-arginine pair on the other.
      Allosteric activators of mammalian adenylyl cyclase, forskolin and the
      stimulatory G protein alpha subunit, promote the catalytically optimal
      juxtaposition of the two domains.

PMID- 9914258
TI  - Unraveling the structures and modes of action of bacterial toxins.
AB  - The mechanism by which a soluble protein converts into a protein that spans a
      membrane remains a central question in understanding the molecular mechanism of
      toxicity of bacterial protein toxins. Using crystallographic structures of
      soluble toxins as templates, the past year has seen a number of experiments that
      are designed to probe the membrane state using other structural methods. In
      addition, crystallographic information concerning the clostridial neurotoxins has
      emerged, suggesting a novel mechanism of pore formation and new relationships
      between toxin binding domains.

PMID- 9914259
TI  - Structure, evolution and action of vitamin B6-dependent enzymes.
AB  - The number of known three-dimensional structures of vitamin B6-dependent enzymes
      has doubled in the past two years. A fourth type of fold for B6-dependent
      enzymes, involving a TIM-barrel domain, has been discovered. Alanine racemase is
      the first known representative of this new fold. Significant progress has been
      made in understanding the allosteric effects in the tryptophan synthase reaction.

PMID- 9914260
TI  - Tubulin structure: insights into microtubule properties and functions.
AB  - The structure of tubulin has recently been determined by electron
      crystallography, paving the way for a clearer understanding of the unique
      properties of tubulin that allow its varied functions within the cell. Some of
      the ongoing work on tubulin can be interpreted in terms of its structure, which
      can serve to guide future studies.

PMID- 9914261
TI  - Conformational changes and disease--serpins, prions and Alzheimer's.
AB  - Some of the most perplexing disorders in medicine are each now known to arise
      from the conformational instability of an underlying protein. The consequence is
      a continuum of pathologies with typically a change in fold leading to ordered
      aggregation and tissue deposition. The serpins provide a structural prototype for
      these pathologies and give a perspective on the assessment of current proposals
      as to the conformational basis of both Alzheimer's disease and the transmissible
      prion encephalopathies.

PMID- 9914262
TI  - Cultured insect mushroom body neurons express functional receptors for
      acetylcholine, GABA, glutamate, octopamine, and dopamine.
AB  - Fluorescence calcium imaging with fura-2 and whole cell, patch-clamp
      electrophysiology was applied to cultured Kenyon cells (interneurons) isolated
      from the mushroom bodies of adult crickets (Acheta domesticus) to demonstrate the
      presence of functional neurotransmitter receptors. In all cells investigated, 5
      microM acetylcholine (ACh, n = 52) evoked an increase in intracellular free
      calcium ([Ca2+]i). Similar effects were observed in response to 10 microM
      nicotine. The ACh response was insensitive to atropine (50 microM) but was
      reduced by mecamylamine (50 microM) and alpha-bungarotoxin (alpha-bgt, 10
      microM). ACh-induced inward ion currents (n = 28, EACh approximately 0 mV) were
      also blocked by 1 microM mecamylamine and by 1 microM alpha-bgt. Nicotine-induced
      inward currents desensitized more rapidly than ACh responses. Thus functional
      alpha-bgt-sensitive nicotinic ACh receptors are abundant on all Kenyon cells
      tested, and their activation leads to an increase in [Ca2+]i. gamma-Aminobutyric
      acid (GABA, 100 microM) triggered a sustained decrease in [Ca2+]i. Similar
      responses were seen with a GABAA agonist, muscimol (100 microM), and a GABAB
      agonist, 3-APPA (1 mM), suggesting that more than one type of GABA receptor can
      affect [Ca2+]i. This action of GABA was not observed when the extracellular KCl
      concentration was lowered. All cells tested (n = 26) with patch-clamp
      electrophysiology showed picrotoxinin (PTX)-sensitive, GABA-induced (30-100
      microM) currents with a chloride-sensitive reversal potential. Thus, an
      ionotropic PTX-sensitive GABA receptor was found on all Kenyon cells tested. Most
      (61%) of the 54 cells studied responded to -glutamate (100 microM) application
      either with a biphasic increase in [Ca2+]i or with a single, delayed, sustained
      [Ca2+]i increase. Nearly all cells tested (95%, n = 19) responded to (100 microM)
      -glutamate with rapidly desensitizing, inward currents that reversed at
      approximately -30 mV. Dopamine (100 microM) elicited either a rapid or a delayed
      increase in [Ca2+]i in 63% of the 26 cells tested. The time course of these
      responses varied greatly among cells. Dopamine failed to elicit currents in patch
      clamped cells (n = 4). A brief decrease in [Ca2+]i was induced by octopamine (100
      microM) in approximately 54% of the cells tested (n = 35). However, when
      extracellular CaCl2 was lowered, octopamine triggered a substantial increase in
      [Ca2+]i in 35% of the cells tested (n = 26). No octopamine-elicited currents were
      detected in patched-clamped cells (n = 10).

PMID- 9914263
TI  - Current-source density analysis in the rat olfactory bulb: laminar distribution
      of kainate/AMPA- and NMDA-receptor-mediated currents.
AB  - The one-dimensional current-source density method was used to analyze laminar
      field potential profiles evoked in rat olfactory bulb slices by stimulation in
      the olfactory nerve (ON) layer or mitral cell layer (MCL) and to identify the
      field potential generators and the characteristics of synaptic activity in this
      network. Single pulses to the ON evoked a prolonged (>/=400 ms) sink (S1ON) in
      the glomerular layer (GL) with corresponding sources in the external plexiform
      layer (EPL) and MCL and a relatively brief sink (S2ON) in the EPL, reversing in
      the internal plexiform and granule cell layers. These sink/source distributions
      suggested that S1ON and S2ON were generated in the apical dendrites of
      mitral/tufted cells and granule cells, respectively. The kainate/AMPA-receptor
      antagonist CNQX (10 microM) reduced the early phase of S1ON, blocked S2ON, and
      revealed a low amplitude, prolonged sink at the location of S2ON in the EPL.
      Reduction of Mg2+, in CNQX, enhanced both the CNQX-resistant component of S1ON
      and the EPL sink. This EPL sink reversed below the MCL, suggesting it was
      produced in granule cells. The NMDA-receptor antagonist APV (50 microM)
      reversibly blocked the CNQX-resistant field potentials in all layers. Single
      pulses were applied to the MCL to antidromically depolarize the dendrites of
      mitral/tufted cells. In addition to synaptic currents of granule cells, a low
      amplitude, prolonged sink (S1mcl) was evoked in the GL. Corresponding sources
      were in the EPL, suggesting that S1mcl was generated in the glomerular dendritic
      tufts of mitral/tufted cells. Both S1mcl and the granule cell currents were
      nearly blocked by CNQX (10 microM) but enhanced by subsequent reduction of Mg2+;
      these currents were blocked by APV. S1mcl also was enhanced by gamma-aminobutyric
      acid-A-receptor antagonists applied to standard medium; this enhancement was
      reduced by APV. ON activation produces prolonged excitation in the apical
      dendrites of mitral/tufted cells, via kainate/AMPA and NMDA receptors, providing
      the opportunity for modulation and integration of sensory information at the
      first level of synaptic processing in the olfactory system. Granule cells respond
      to input from the lateral dendrites of mitral/tufted cells via both kainate/AMPA
      and NMDA receptors; however, in physiological concentrations of extracellular
      Mg2+, NMDA-receptor activation does not contribute significantly to the granule
      cell responses. The glomerular sink evoked by antidromic depolarization of
      mitral/tufted cell dendrites suggests that glutamate released from the apical
      dendrites of mitral/tufted cells may excite the same or neighboring mitral/tufted
      cell dendrites.

PMID- 9914264
TI  - Dopamine modulates two potassium currents and inhibits the intrinsic firing
      properties of an identified motor neuron in a central pattern generator network.
AB  - The two pyloric dilator (PD) neurons are components [along with the anterior
      burster (AB) neuron] of the pacemaker group of the pyloric network in the
      stomatogastric ganglion of the spiny lobster Panulirus interruptus. Dopamine (DA)
      modifies the motor pattern generated by the pyloric network, in part by exciting
      or inhibiting different neurons. DA inhibits the PD neuron by hyperpolarizing it
      and reducing its rate of firing action potentials, which leads to a phase delay
      of PD relative to the electrically coupled AB and a reduction in the pyloric
      cycle frequency. In synaptically isolated PD neurons, DA slows the rate of
      recovery to spike after hyperpolarization. The latency from a hyperpolarizing
      prestep to the first action potential is increased, and the action potential
      frequency as well as the total number of action potentials are decreased. When a
      brief (1 s) puff of DA is applied to a synaptically isolated, voltage-clamped PD
      neuron, a small voltage-dependent outward current is evoked, accompanied by an
      increase in membrane conductance. These responses are occluded by the combined
      presence of the potassium channel blockers 4-aminopyridine and
      tetraethylammonium. In voltage-clamped PD neurons, DA enhances the maximal
      conductance of a voltage-sensitive transient potassium current (IA) and shifts
      its Vact to more negative potentials without affecting its Vinact. This enlarges
      the "window current" between the voltage activation and inactivation curves,
      increasing the tonically active IA near the resting potential and causing the
      cell to hyperpolarize. Thus DA's effect is to enhance both the transient and
      resting K+ currents by modulating the same channels. In addition, DA enhances the
      amplitude of a calcium-dependent potassium current (IO(Ca)), but has no effect on
      a sustained potassium current (IK(V)). These results suggest that DA
      hyperpolarizes and phase delays the activity of the PD neurons at least in part
      by modulating their intrinsic postinhibitory recovery properties. This modulation
      appears to be mediated in part by an increase of IA and IO(Ca). IA appears to be
      a common target of DA action in the pyloric network, but it can be enhanced or
      decreased in different ways by DA in different neurons.

PMID- 9914265
TI  - Voltage-activated currents from adult honeybee (Apis mellifera) antennal motor
      neurons recorded in vitro and in situ.
AB  - Voltage-activated currents from adult honey bee antennal motor neurons were
      characterized with in vitro studies in parallel with recordings taken from cells
      in situ. Two methods were used to ensure unequivocal identification of cells as
      antennal motor neurons: 1) selective backfilling of the neurons with fluorescent
      markers before dissociation for cell culture or before recording from cells in
      intact brains, semiintact brains, or in brain slices or 2) staining with a
      fluorescent marker via the patch pipette during recordings and identifying
      antennal motor neurons in situ on the basis of their characteristic morphology.
      Four voltage-activated currents were isolated in these antennal motor neurons
      with pharmacological, voltage, and ion substitution protocols. The neurons
      expressed at least two distinct K+ currents, a transient current (IA) that was
      blocked by 4-aminopyridine (4-5 x 10(-3) M), and a sustained current (IK(V)) that
      was partially blocked by tetraethylammonium (2-3 x 10(-2) M) and quinidine (5 x
      10(-5) M). IA activated above -40 to -30 mV and the half-maximal voltages for
      steady-state activation and inactivation were -8.8 and -43.2 mV, respectively.
      IK(V) activated above -50 to -40 mV and the midpoint of the steady-state
      activation curve was +11.2 mV. IK(V) did not show steady-state inactivation.
      Additionally, two inward currents were isolated: a tetrodotoxin (10(-7) M)
      sensitive, transient Na+ current (INa) that activated above -35 mV, with a
      maximum around -5 mV and a half-maximal voltage for inactivation of -72.6 mV, and
      a CdCl2 (5 x 10(-5) M)-sensitive Ca2+ current that activated above -45 to -40 mV,
      with a maximum around -15 mV. This study represents the first step in our effort
      to analyze the cellular and ionic mechanisms underlying the intrinsic properties
      and plasticity of antennal motor neurons.

PMID- 9914266
TI  - Extracellular chloride and the maintenance of spontaneous epileptiform activity
      in rat hippocampal slices.
AB  - Previous studies showed that furosemide blocks spontaneous epileptiform activity
      without diminishing synaptic transmission or reducing hyperexcited field
      responses to electrical stimuli. We now test the hypothesis that the
      antiepileptic effects of furosemide are mediated through its blockade of the
      Na+,K+,2Cl- cotransporter and thus should be mimicked by a reduction of
      extracellular chloride ([Cl-]o). In the first set of experiments, field
      recordings from the CA1 cell body layer of hippocampal slices showed that
      spontaneous bursting developed within 10-20 min in slices perfused with low-[Cl
      ]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a
      further 10-20 min. Intracellular recordings from CA1 pyramidal cells showed that
      normal action potential discharge could be elicited by membrane depolarization,
      even after the tissue was perfused with low-[Cl-]o medium for >2 h. In a second
      set of experiments, spontaneous bursting activity was induced in slices by
      perfusion with high-[K+]o (10 mM), bicuculline (100 microM), or 4-aminopyridine
      (100 microM). In each case, recordings from the CA1 region showed that reduction
      of [Cl-]o to 21 mM reversibly blocked the bursting within 1 h. Similar to
      previous observations with furosemide treatment, low-[Cl-]o medium blocked
      spontaneous hypersynchronous discharges without reducing synaptic
      hyperexcitability (i.e., hyperexcitable field responses evoked by electrical
      stimulation). In a third set of experiments, prolonged exposure (>1 h after
      spontaneous bursting ceased) of slices to systematically varied [Cl-]o and [K+]o
      resulted in one of three types of events: 1) spontaneous, long-lasting, and
      repetitive negative field potential shifts (7 mM [Cl-]o; 3 mM [K+]o); 2)
      oscillations consisting of 5- to 10-mV negative shifts in the field potential,
      with a period of approximately 1 cycle/40 s (16 mM [Cl-]o; 12 mM [K+]o); and 3)
      shorter, infrequently occurring negative field shifts lasting 20-40 s (21 mM [Cl
      ]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl-]o on
      neuronal synchronization and spontaneous discharge are time dependent. Similar
      effects were seen with furosemide and low [Cl-]o, consistent with the hypothesis
      that the antiepileptic effect of furosemide is mediated by the drug's effect on
      chloride transporters. Finally, the results of altering extracellular potassium
      along with chloride suggest that blockade of the Na+, K+,2Cl- cotransporter,
      which normally transports chloride from the extracellular space into glial cells,
      is key to these antiepileptic effects.

PMID- 9914267
TI  - Gustatory neural coding in the cortex of the alert cynomolgus macaque: the
      quality of bitterness.
AB  - We sought to define the gustatory neural representation in primates for stimuli
      that humans describe as predominantly bitter. Thus we analyzed the responses of
      single neurons from the insular cortex of two alert, male cynomolgus macaques in
      response to the oral application of four basic taste stimuli (glucose, NaCl, HCl,
      and quinine HCl) and fruit juice, and to a series of 15 other chemicals to which
      humans ascribe a bitter component. Gustatory neurons occupied a volume of 109 mm3
      across an area of 4.0 mm in the anterposterior plane, 4.4 mm in the mediolateral,
      and 6.2 mm in the dorsoventral. Taste cells represented 161 (8.6%) of the 1881
      neurons tested for chemical sensitivity. Fifty of these could be monitored
      throughout the delivery of the entire stimulus series, and their responses
      constitute the data of this study. The mean spontaneous discharge rate of the
      cortical gustatory cells was 3.2 +/- 3.3 spikes/s (range = 0.2-17.7 spikes/s).
      The mean breadth-of-tuning coefficient was a moderate 0.77 +/- 0.15 (range = 0.25
      0.99). Forty-eight neurons responded to taste stimuli with excitation, and two
      responded with inhibition. Forty-one of the 50 neurons were able to be classified
      into one of four functional types based on their responses to the four basic
      stimuli used here. These were sugar (n = 22), salt (n = 7), acid (n = 7), and
      quinine (n = 5). A two-dimensional space was generated from correlations among
      the response profiles elicited by the stimuli array. The 16 bitter chemicals
      formed a coherent group that was most closely related to HCl, moderately to NaCl,
      and bore no relationship with glucose. Within the bitter stimuli, six formed a
      subgroup that was most separated from all nonbitter chemicals: quinine HCl,
      phenlythiocarbamide, propylthiouracil, caffeine, theophylline, and phenylalanine.
      Humans describe these stimuli as rather purely bitter. Of the remaining 10 bitter
      compounds, 4 were on the fringe of the bitter group leading to NaCl: MgCl2,
      CaCl2, NH4Cl, and arginine. Humans characterize these as bitter-salty. Three were
      on the fringe leading to HCl: urea, cysteine and vitamin B1. Humans call these
      bitter-sour. The remaining three (nicotine, histidine, and vitamin B2) occupied
      the center of the bitter group. Taste quality, inferred from the position of each
      stimulus in the space, correlated well with human descriptions of the same
      stimuli, reinforcing the value of the macaque as a neural model for human
      gustation.

PMID- 9914269
TI  - Retention of hindlimb stepping ability in adult spinal cats after the cessation
      of step training.
AB  - Adult spinal cats were trained to perform bipedal hindlimb locomotion on a
      treadmill for 6-12 wk. After each animal acquired the ability to step, locomotor
      training was withheld, and stepping was reexamined 6 and 12 wk after training
      ended. The performance characteristics, hindlimb muscle electromyographic
      activity patterns, and kinematic characteristics of the step cycle that were
      acquired with training were largely maintained when training was withheld for 6
      wk. However, after 12 wk without training, locomotor performance declined, i.e.,
      stumbling was more frequent, and the ability to consistently execute full weight
      bearing steps at any treadmill speed decreased. In addition, the height that the
      paw was lifted during the swing phase decreased, and a smaller range of extension
      in the hindlimbs occurred during the E3 phase of stance. When three of the spinal
      cats underwent 1 wk of retraining, stepping ability was regained more rapidly
      than when trained initially. The finding that stepping ability in trained adult
      spinal cats can persist for 6 wk without training provides further evidence that
      training-induced enhancement of stepping is learned in the spinal cats and that a
      memory of the enhanced stepping is stored in the spinal networks. However, it
      appears that the spinal cord can forget how to consistently execute stepping if
      that task is not practiced for 12 wk. The more rapid learning that occurred with
      retraining is also consistent with a learning phenomenon. These results in
      conjunction with our earlier findings suggest that the efficacy of the neural
      pathways that execute a motor task is highly dependent on the periodic activation
      of those pathways in a sequence compatible with that motor task.

PMID- 9914268
TI  - Muscarine modulates Ca2+ channel currents in rat sensorimotor pyramidal cells via
      two distinct pathways.
AB  - We used the whole cell patch-clamp technique and single-cell reverse
      transcription-polymerase chain reaction (RT-PCR) to study the muscarinic receptor
      mediated modulation of calcium channel currents in both acutely isolated and
      cultured pyramidal neurons from rat sensorimotor cortex. Single-cell RT-PCR
      profiling for muscarinic receptor mRNAs revealed the expression of m1, m2, m3,
      and m4 subtypes in these cells. Muscarine reversibly reduced Ca2+ currents in a
      dose-dependent manner. The modulation was blocked by the muscarinic antagonist
      atropine. When the internal recording solution included 10 mM ethylene glycol
      bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA) or 10 mM bis-(o
      aminophenoxy)-N,N,N', N'-tetraacetic acid (BAPTA), the modulation was rapid
      (tauonset approximately 1.2 s). Under conditions where intracellular calcium
      levels were less controlled (0.0-0.1 mM BAPTA), a slowly developing component of
      the modulation also was observed (tauonset approximately 17 s). Both fast and
      slow components also were observed in recordings with 10 mM EGTA or 20 mM BAPTA
      when Ca2+ was added to elevate internal [Ca2+] ( approximately 150 nM). The fast
      component was due to a reduction in both N- and P-type calcium currents, whereas
      the slow component involved L-type current. N-ethylmaleimide blocked the fast
      component but not the slow component of the modulation. Preincubation of cultured
      neurons with pertussis toxin (PTX) also greatly reduced the fast portion of the
      modulation. These results suggest a role for both PTX-sensitive G proteins as
      well as PTX-insensitive G proteins in the muscarinic modulation. The fast
      component of the modulation was reversed by strong depolarization, whereas the
      slow component was not. Reblock of the calcium channels by G proteins (at -90 mV)
      occurred with a median tau of 68 ms. We conclude that activation of muscarinic
      receptors results in modulation of N- and P-type channels by a rapid, voltage
      dependent pathway and of L-type current by a slow, voltage-independent pathway.

PMID- 9914270
TI  - Potassium currents in precursor cells isolated from the anterior subventricular
      zone of the neonatal rat forebrain.
AB  - The progenitor cells from the anterior part of the neonatal subventricular zone,
      the SVZa, are unusual in that, although they undergo division, they have a
      neuronal phenotype. To characterize the electrophysiological properties of the
      SVZa precursor cells, recordings were made of potassium and sodium currents from
      SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day.
      The properties of the delayed rectifier and A-type potassium currents were
      described by classical Hodgkin and Huxley analyses of activation and
      inactivation. In addition, cells were assessed under current clamp for their
      ability to generate action potentials. The A-type potassium current (IK(A)) was
      completely inactivated at a holding potential of -50 mV. The remaining potassium
      current resembled the delayed rectifier current (IK(DR)) in that it was blocked
      by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly
      compared with IK(A). The conductance-voltage (G-V) curve revealed that G
      increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20
      mV, and then decreased for voltages above +30 mV. Activation time constants were
      largest at -40 mV ( approximately 11 ms) and smallest at 100 mV ( approximately
      1.5 ms). The properties of IK(A) were studied in the presence of 20 mM TEA, to
      block IK(DR), and from a holding potential of -15 mV, to inactivate both IK(DR)
      and IK(A). IK(A) was then allowed to recover from inactivation to negative
      potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest
      at -130 mV ( approximately 21 ms) and slowest at -90 mV ( approximately 135 ms).
      Inactivation was voltage independent from -60 to +60 mV with a time constant of
      approximately 15 ms. At steady state, IK(A) was half inactivated at -90 mV. GK(A)
      increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the
      activation time constants ranged from approximately 1.9 ms at -50 mV to 0.7 ms at
      +60 mV. The properties of IK(A) resembled those of IK(A) found in differentiating
      cerebellar granule neurons. Most SVZa cells had sodium currents (28/32 cells).
      However, in current clamp 11 of 12 cells were incapable of generating action
      potentials from voltages of -30 to -100 mV, suggesting that the available current
      densities were too low to support excitability.

PMID- 9914271
TI  - P42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic
      plasticity in rat dentate gyrus in vitro.
AB  - The effects of the specific p42/44 mitogen-activated protein (MAP) kinase cascade
      inhibitor, PD98059, were investigated on three types of long-term potentiation
      (LTP) in the medial perforant path of the rat dentate gyrus in vitro: LTP induced
      by 1) high-frequency stimulation (HFS-LTP), 2) application for 10 min of the K+
      channel blocker, tetraethylammonium chloride (TEA-LTP), and 3) application of the
      metabotropic glutamate receptor (mGluR) agonist (S)-dihydrophenylglycine (S-DHPG)
      for 2 min (DHPG-LTP). Bath perfusion of PD98059 (50 microM) for 1 h inhibited HFS
      LTP (111 +/- 5%, mean +/- SE, at 90 min posttetanus in test slices compared with
      144 +/- 5% in control slices; n = 6-7). Concentrations of 10 and 20 microM
      PD98059 had no effect on HFS-LTP (n = 6). PD98059 (50 microM) had no effect on
      the isolated N-methyl--aspartate excitatory postsynaptic potential (NMDA-EPSP) or
      on the maintenance phase of HFS-LTP. PD98059 (50 microM) did not affect paired
      pulse depression (PPD; interstimulus intervals of 10 and 100 ms) of synaptic
      transmission as is typically observed in the medial perforant path of the dentate
      gyrus. Bath application of (S)-DHPG (40 microM) for 2 min gave rise to a
      potentiation of the EPSPs slope (148 +/- 4% at 1 h post-DHPG wash out; n = 5).
      Pretreatment of slices with PD98059 (50 microM) inhibited the DHPG-LTP (98 +/- 3%
      at 1 h post-DHPG wash out; n = 5). The TEA-LTP (125 +/- 4% at 1 h post-TEA wash
      out; n = 6) was found to be both -2-amino-5-phosphonopentanoic acid (-AP5; 100
      microM) and nifedipine (20 microM) independent. However, the T type voltage
      dependent calcium-channel blocker, NiCl2 (50 microM), completely inhibited the
      observed potentiation. The mGluR receptor antagonist alpha-methyl-4-carboxy
      phenyl glycine (MCPG; 100 microM) and PD98059 (50 microM) caused a complete block
      of the TEA-LTP. These data show for the first time an involvement of the p42/44
      MAP kinase in the induction and expression of both an NMDA-dependent and two
      forms of NMDA-independent LTP in the dentate gyrus.

PMID- 9914272
TI  - Developmental changes in the nicotinic responses of ciliary ganglion neurons.
AB  - The accumulation of functional neurotransmitter receptors by neurons during
      development is an essential part of synapse formation. Chick ciliary ganglion
      neurons express two kinds of nicotinic receptors. One is abundant, contains the
      alpha7 gene product, rapidly desensitizes, and binds alpha-bungarotoxin. The
      other is less abundant, contains multiple gene products (alpha3, beta4, alpha5,
      and beta2 subunits), slowly desensitizes, and binds the monoclonal antibody mAb
      35. Rapid application of agonist to freshly dissociated neurons elicits responses
      from both classes of receptors. Between embryonic days 8 and 15, the whole cell
      response of alpha3-containing receptors increases fivefold in peak amplitude and,
      normalized for cell growth, 1.7-fold in current density. In addition, the
      response decays more slowly in older neurons, suggesting a developmental decrease
      in the rate of desensitization. The whole cell response of alpha7-containing
      receptors increases 10-fold in peak amplitude over the same period and 3-fold in
      current density. No change in the rate of desensitization was apparent for alpha7
      containing receptors with developmental age, but analysis was limited by overlap
      in responses from the two kinds of receptors. Indirect immunofluorescence
      measurements on dissociated neurons showed that the relative levels of alpha7
      containing receptors on the soma increased during development to the same extent
      as the whole cell response attributed to them. In contrast, the relative levels
      of alpha3-containing receptors increased more during the same time period than
      did the whole cell response they generated. The immunofluorescence analysis also
      showed that both classes of receptors become distributed in prominent clusters on
      the cell surface as a function of developmental age. The results indicate that
      during this period of synaptic consolidation on the neurons, the two major
      classes of functional nicotinic receptors undergo substantial upregulation;
      alpha3-containing receptors as a class may undergo changes in receptor properties
      as well.

PMID- 9914273
TI  - Critical period for the monocular deprivation effect in rats: assessment with
      sweep visually evoked potentials.
AB  - Rats and mice are the species most frequently used for cellular and biochemical
      studies of plasticity, but only a few studies have examined developmentally
      regulated visual plasticity in these species. Here we report a study of the
      critical period for monocular deprivation in Long-Evans rats in which visual
      pattern sweep evoked potentials (sweep VEP) was used. Successful recording of
      sweep VEPs depended on establishing a stable light plane of anesthesia. We found
      a mixture of halothane and NO2 to be suitable. During a single trial lasting 10
      s, anesthetized rats (n = 28) viewed a sinusoidal contrast grating (spatial
      frequency of 0.13 cycles/deg) that reversed phase at 3 Hz. During the trial, the
      grating contrast increased logarithmically from 1 to 70%. Extracellular recording
      pipettes were placed bilaterally in layers II/III of the binocular regions of
      primary visual cortex. Stimulating the right and left eye on alternate trials,
      sweep VEP amplitudes were collected for 30 trials from each eye. In monocularly
      deprived animals, the right eyelid had been sutured for 5 days before recording.
      Age at suture varied from P19 to P86. In 12 of 13 rats sutured between P19 and
      P50, the crossed response from the deprived eye was smaller than the crossed
      response from the nondeprived eye. The same relation prevailed for the uncrossed
      responses in 11 of 13 animals. There was no significant monocular deprivation
      effect in animals sutured between P55 and P86 (n = 9). Dark rearing until
      approximately P90 followed by 5 days of eyelid suture resulted in a strong
      monocular deprivation effect in both crossed and uncrossed pathways (n = 3).
      There was little effect of dark rearing alone on the size the sweep VEPs (n = 3).
      The critical period reported here lasts at least 2 wk longer than reported for
      rats by Fagliolini et al. and for mice by Gordon and Stryker. Both previous
      studies used single unit recording rather than the sweep VEP method.

PMID- 9914274
TI  - Studies on the corticospinal control of human walking. I. Responses to focal
      transcranial magnetic stimulation of the motor cortex.
AB  - Experiments were done to determine the extent to which the corticospinal tract is
      linked with the segmental motor circuits controlling ankle flexors and extensors
      during human walking compared with voluntary motor tasks requiring attention to
      the level of motor activity. The motor cortex was activated transcranially using
      a focal magnetic stimulation coil. For each subject, the entire input-output (I
      O) curve [i.e., the integral of the motor evoked-potential (MEP) versus stimulus
      strength] was measured during a prescribed tonic voluntary contraction of either
      the tibialis anterior (TA) or the soleus. Similarly, I-O curves were measured in
      the early part of the swing phase, or in the early part of the stance phase of
      walking. The I-O data points were fitted by the Boltzmann sigmoidal function,
      which accounted for >/=80% of total data variance. There was no statistically
      significant difference between the I-O curves of the TA measured during voluntary
      ankle dorsiflexion or during the swing phase of walking, at matched levels of
      background electromyographic (EMG) activity. Additionally, there was no
      significant difference in the relation between the coefficient of variation and
      the amplitude of the MEPs measured in each task, respectively. In comparison,
      during the stance phase of walking the soleus MEPs were reduced on average by 26%
      compared with their size during voluntary ankle plantarflexion. Furthermore,
      during stance the MEPs in the inactive TA were enhanced relative to their size
      during voluntary ankle plantarflexion and in four of six subjects the TA MEPs
      were larger than those of the soleus. Finally, stimulation of the motor cortex at
      various phases of the step cycle did not reset the cycle. The time of the next
      step occurred at the expected moment, as determined from the phase-resetting
      curve. One interpretation of this result is that the motor cortex may not be part
      of the central neural system involved in timing the motor bursts during the step
      cycle. We suggest that during walking the corticospinal tract is more closely
      linked with the segmental motor circuits controlling the flexor, TA, than it is
      with those controlling the extensor, soleus. However, during voluntary tasks
      requiring attention to the level of motor activity, it is equally linked with the
      segmental motor circuits of ankle flexors or extensors.

PMID- 9914275
TI  - Voltage-activated K+ currents of hypoglossal motoneurons in a brain stem slice
      preparation from the neonatal rat.
AB  - Whole cell, patch-clamp recordings were performed on motoneurons of the
      hypoglossus nucleus in a brain stem slice preparation from the neonatal rat
      brain. The aim was to investigate transient outward currents activated by
      membrane depolarization under voltage clamp conditions. In a Ca2+-free medium
      containing tetrodotoxin and Cs+, depolarizing voltage commands from a holding
      potential of -50 mV induced slow outward currents (Islow) with 34 +/- 6 ms (SE)
      onset time constant at 0 mV and minimal decline during a 1 s pulse
      depolarization. When the depolarizing command was preceded by a prepulse to -110
      mV, the outward current became biphasic as it comprised a faster component
      (Ifast), which could be investigated in isolation by subtracting the two sets of
      records. Ifast showed rapid kinetics (9 +/- 4 ms 10-90% rise time and 70 +/- 20
      ms decay time constant at 0 mV) and strong voltage-dependent inactivation (half
      inactivation was at -92.9 +/- 0.2 mV) from which it readily recovered with a
      biexponential timecourse (4.4 +/- 0.6 and 17 +/- 2 ms time constants at -110 mV
      membrane potential). Islow was selectively blocked by TEA (10-30 mM) while Ifast
      was preferentially depressed by 2-3 mM 4-aminopyridine. Analysis of tail current
      reversal indicated that both Islow and Ifast were predominantly due to K+ with
      minor permeability to Na+ (92/1 and 50/1, respectively). These results suggest
      that membrane depolarization activated distinct K+ conductances that, in view of
      their largely dissimilar kinetics, are likely to play a differential role in
      regulating the firing behavior of hypoglossal motoneurons.

PMID- 9914277
TI  - Focal epileptogenesis in a rat model of polymicrogyria.
AB  - Polymicrogyria, a developmental cortical malformation associated with epilepsy,
      can be modeled in rats with a transcortical freeze lesion on the day of birth
      (P0) or P1. We have used field potential recordings to characterize the
      incidence, propagation patterns, and distribution of epileptiform activity in
      slices from rats with experimental microgyri. Interictal-like epileptiform
      activity was evoked in slices from 85% of freeze-lesioned rats aged P12-P118.
      These data show age-specific properties of epileptogenesis, including: a delay in
      onset, a decrease in the incidence of epileptiform activity in rats >P40 that was
      specific to those lesioned on P0 as opposed to P1, and a shift in the likely site
      of initiation to areas further from the microgyrus in mature animals. Several
      observations suggest that the area adjacent to the microgyrus, which appears
      histologically normal in Nissl stains, contains the necessary epileptogenic
      neuronal circuits: 1) in 78% of slices, epileptiform activity could be evoked
      only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not
      within the microgyrus proper; 2) epileptiform activity consistently originated
      from a particular site within this paramicrogyral zone, independent of the
      location of the stimulating electrode, suggesting that the generator is outside
      of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex
      were unaltered after separation of this zone from the microgyrus with a
      transcortical cut; and 4) the short-latency graded field potential evoked in the
      paramicrogyral zone contained an additional negativity not seen in control
      slices. The epileptiform activity was blocked reversibly by N-methyl--aspartate
      receptor antagonists in slices from mature as well as immature freeze-lesioned
      rats. These results suggest that aberrant synaptic connectivity develops in rat
      cortex surrounding the microgyrus and produces a focal epileptogenic zone whose
      capacity to generate epileptiform activities does not depend on connections with
      the malformation itself. We hypothesize that afferents, originating from cortical
      and extracortical sites, lose their targets in the region of the malformation and
      make appropriate laminar contacts in the cortex adjacent to the malformation,
      creating an overabundance of excitatory input to this cortical zone. Increased
      excitatory feedback onto specific cortical elements may be one factor involved in
      epileptogenesis in this model of a cortical malformation.

PMID- 9914276
TI  - Dopamine modulates inwardly rectifying hyperpolarization-activated current (Ih)
      in cultured rat olfactory receptor neurons.
AB  - The presence of dopamine receptors in olfactory receptor neurons (ORNs) suggests
      that odor sensitivity may be modulated by neurotransmitters at the level of
      primary sensory neurons. Using standard patch-clamp techniques on rat ORNs, we
      found that 1 microM dopamine, 500 microM SQ 22536 (SQ, an adenylyl cyclase
      inhibitor), 20 and 50 microM quinpirole (a selective dopamine D2 receptor
      agonist), and 1 mM adenosine 3', 5'-cyclic monophosphate (cAMP) modulate the
      hyperpolarization-activated current Ih. On hyperpolarizing from a holding
      potential of -58 mV, a small Cs+-sensitive inwardly rectifying current (Ih) was
      observed. Increases in extracellular K+ increased Ih amplitude without shifting
      its voltage dependence of activation, whereas increases in temperature produced
      an increase in Ih amplitude and a hyperpolarizing shift in the activation curve.
      Application of 1 microM dopamine reversibly shifted Ih activation to more
      negative potentials and decreased Ih current amplitudes. These effects were
      blocked by concomitant application of dopamine with sulpiride, a selective
      dopamine D2 receptor antagonist. The effects of dopamine were mimicked by
      quinpirole. Quinpirole (20 microM) decreased Ih current amplitude, but was
      without effect on Ih voltage dependence of activation. However, 50 microM
      quinpirole produced both a reduction of Ih peak currents and a hyperpolarizing
      shift in the activation curve for Ih. External application of the adenylyl
      cyclase inhibitor SQ 22536 produced a reversible decrease in peak currents but
      had no effect on Ih voltage dependence of activation, whereas internal
      application of cAMP shifted Ih activation to more depolarized potentials. Because
      Ih modulates cell excitability and spike frequency adaptation, our findings
      support a role for dopamine in modulating the sensitivity and output of rat ORNs
      to odorants.

PMID- 9914278
TI  - Intraneuronal [Ca2+] changes induced by 2-deoxy-D-glucose in rat hippocampal
      slices.
AB  - Temporary replacement of glucose by 2-deoxyglucose (2-DG; but not sucrose) is
      followed by long-term potentiation of CA1 synaptic transmission (2-DG LTP), which
      is Ca2+-dependent and is prevented by dantrolene or N-methyl--aspartate (NMDA)
      antagonists. To clarify the mechanism of action of 2-DG, we monitored [Ca2+]i
      while replacing glucose with 2-DG or sucrose. In slices (from Wistar rats) kept
      submerged at 30 degreesC, pyramidal neurons were loaded with [Ca2+]-sensitive
      fluo-3 or Fura Red. The fluorescence was measured with a confocal microscope.
      Bath applications of 10 mM 2-DG (replacing glucose for 15 +/- 0.38 min, means +/-
      SE) led to a rapid but reversible rise in fluo-3 fluorescence (or drop of Fura
      Red fluorescence); the peak increase of fluo-3 fluorescence (DeltaF/F0), measured
      near the end of 2-DG applications, was by 245 +/- 50% (n = 32). Isosmolar sucrose
      (for 15-40 min) had a smaller but significant effect (DeltaF/F0 = 94 +/- 14%, n =
      10). The 2-DG-induced DeltaF/F0 was greatly reduced (to 35 +/- 15%, n = 16) by,
      aminophosphono-valerate (50-100 microM) and abolished by 10 microM dantrolene (
      4.0 +/- 2.9%, n = 11). A substantial, although smaller effect, of 2-DG persisted
      in Ca2+-free 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N', N'
      tetraacetic acid (EGTA) medium. Two adenosine antagonists, which do not prevent 2
      DG LTP, were also tested; 2-DG-induced DeltaF/F0 (fluo-3) was not affected by the
      A1 antagonist 8-cyclopentyl-3, 7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX
      50 nM; 287 +/- 38%; n = 20), but it was abolished by the A1/A2 antagonist 8-SPT;
      25 +/- 29%, n = 19). These observations suggest that 2-DG releases glutamate and
      adenosine and that the rise in [Ca2+] may be triggered by a synergistic action of
      glutamate (acting via NMDA receptors) and adenosine (acting via A2b receptors)
      resulting in Ca2+ release from a dantrolene-sensitive store. The discrepant
      effects of sucrose and 8-SPT on DeltaF/F0, on the one hand, and 2-DG LTP, on the
      other, support other evidence that increases in postsynaptic [Ca2+]i are not
      essential for 2-DG LTP.

PMID- 9914279
TI  - Zinc and flunitrazepam modulation of GABA-mediated currents in rat
      suprachiasmatic neurons.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for
      generating circadian rhythms in mammals, and GABA is the predominant
      neurotransmitter in the SCN. Properties of gamma-aminobutyric acid-A (GABAA)
      responses in SCN neurons were examined in acutely prepared hypothalamic slices
      from 3- to 8-wk-old rats with the use of whole cell voltage-clamp techniques.
      Zn2+ reduced the amplitude of GABAA-mediated spontaneous inhibitory postsynaptic
      currents (sIPSCs) in a concentration-dependent manner ranging from a reduction of
      control amplitude to 88% at 10 microM to 27% at 1,000 microM. Zn2+ reduced IPSC
      amplitude to a similar degree in the presence of tetrodotoxin and also
      significantly reduced the amplitude of currents evoked by application of
      exogenous GABA (100 microM, pressure applied). Zn2+ increased the frequency of
      IPSCs at lower concentrations and decreased it at higher ones. Flunitrazepam (100
      nM) usually failed to potentiate the amplitude of sIPSCs, but prolonged sIPSC
      kinetics. Two exponential components were normally resolved in the sIPSC decay
      constants, and flunitrazepam significantly increased those two components. Thus
      flunitrazepam increased the duration of sIPSCs and potentiated the amplitude of
      currents evoked by pressure application of GABA. Zn2+ and benzodiazepine each
      modulated the effect of GABA in nearly all cells, suggesting that most SCN
      neurons have a similar GABAA receptor subunit composition in this respect. Zn2+
      also affected sIPSC frequency, which suggests that Zn2+ increased neuronal firing
      rate at lower concentrations. These results begin to define the cellular roles
      that these GABAA receptor modulators might play in circadian regulation.

PMID- 9914280
TI  - Properties and sex-specific differences of GABAA receptors in neurons expressing
      gamma1 subunit mRNA in the preoptic area of the rat.
AB  - Gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial
      preoptic area (mPOA) are known to play a critical role in regulating sexual and
      neuroendocrine functions. In the rat brain, high levels of expression of the
      gamma1 subunit mRNA of the GABAA receptor are restricted to a limited number of
      regions that mediate sexual behaviors, including the mPOA. The biophysical and
      pharmacological profiles of native gamma1-containing receptors in neurons are
      unknown. Here, we have characterized the properties of GABAA receptor-mediated
      spontaneous inhibitory postsynaptic currents (sIPSCs) and currents elicited by
      fast perfusion of GABA to isolated mPOA neurons of juvenile male and female rats.
      No significant sex-specific differences were evident in the mean peak amplitude,
      distribution of event amplitudes, kinetics of current decay, or the frequency of
      sIPSCs. The profile of modulation of sIPSCs by diazepam, beta-CCM and zolpidem,
      allosteric modulators that act at the benzodiazepine (BZ) site of the GABAA
      receptor, support the assertion that mPOA neurons of both sexes express
      functional gamma1-containing receptors. The ability of zolpidem to modulate both
      sIPSC amplitude and currents elicited by rapid perfusion of GABA to mPOA neurons
      differed significantly between the sexes. Zolpidem reversibly induced negative
      modulation of currents in mPOA neurons isolated from male rats, but had no effect
      in mPOA neurons from female rats. Concentration-response analysis of responses in
      neurons acutely isolated from male rats indicated an IC50 of 58 nM with maximal
      decreases of approximately 50% of control peak current amplitude. In situ
      hybridization analysis demonstrated that levels of the gamma1 subunit mRNA are
      significantly higher in mPOA neurons from male than female rats. No significant
      sex-specific differences were detected in the levels of alpha1, alpha2, or alpha5
      mRNAs. These results suggest that native gamma1-containing receptors are
      expressed in primary neurons of the mPOA and that sex-specific differences in the
      expression of this subunit may contribute to sexual dimorphism in GABAA receptor
      modulation by compounds acting at the BZ site.

PMID- 9914282
TI  - Serotonin modulates spike backpropagation and associated [Ca2+]i changes in the
      apical dendrites of hippocampal CA1 pyramidal neurons.
AB  - The effect of serotonin (5-HT) on somatic and dendritic properties was analyzed
      in pyramidal neurons from the CA1 region in slices from the rat hippocampus. Bath
      applied 5-HT (10 microM) hyperpolarized the soma and apical dendrites and caused
      a conductance increase at both locations. In the dendrites (200-300 microm from
      the soma) trains of antidromically activated, backpropagating action potentials
      had lower peak potentials in 5-HT than in normal artificial cerebrospinal fluid.
      Spike amplitudes were about the same in the two solutions. Similar results were
      found when the action potentials were evoked synaptically with stimulation in the
      stratum oriens. In the soma, spike amplitudes increased in 5-HT, with only a
      small decrease in the peak potential. Calcium concentration measurements, made
      with bis-fura-2 injected through patch electrodes, showed that the amplitude of
      the [Ca2+]i changes was reduced at all locations in 5-HT. The reduction of the
      [Ca2+]i change in the soma was confirmed in slices where cells were loaded with
      fura-2-AM. The reduction at the soma in 5-HT, where the spike amplitude
      increased, suggests that the reduction is due primarily to direct modulation of
      Ca2+ channels. In the dendrites, the reduction is due to a combination of this
      channel modulation and the lowering of the peak potential of the action
      potentials.

PMID- 9914281
TI  - Injection of MK-801 affects ocular dominance shifts more than visual activity.
AB  - Kittens were given intramuscular injections of the N-methyl--aspartate (NMDA)
      antagonist MK-801 twice daily (morning and midday) during the peak of the period
      of susceptibility for ocular dominance changes. They were then exposed to light
      with one eye closed for 4 h after each injection. The ocular dominance of these
      kittens was shifted significantly less than that of kittens injected with saline
      and exposed to light over the same period at the same age. After recording a
      sample of cells for an ocular dominance histogram, the kittens were injected with
      the same dose of MK-801 that was used during rearing to observe its effect on the
      activity of single cells in the visual cortex. In the majority of cells (7/13)
      there was no significant change in activity. Positive evidence for a reduction in
      activity was seen in only a minority (3/13) of cells. In a separate series of
      experiments, dose-response curves were measured for cells in the visual cortex in
      response to iontophoresis of NMDA or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA), and the effect of an injection of MK-801 on these
      curves was measured. MK-801, at doses similar to those used in the ocular
      dominance experiments, had a significant effect on the dose-response curves for
      NMDA, but little effect on the dose-response curves for AMPA, or the visual
      responses of the cells. We conclude that ocular dominance shifts can be reduced
      significantly by a treatment that has little effect on the level of activity of
      cells in the visual cortex but does specifically affect the responses of the
      cells to NMDA as opposed to the responses to AMPA.

PMID- 9914283
TI  - Norepinephrine inhibits a toxin resistant Ca2+ current in carotid body glomus
      cells: evidence for a direct G protein mechanism.
AB  - Previous studies have demonstrated that endogenous norepinephrine (NE) inhibits
      carotid body (CB) sensory discharge, and the cellular actions of NE have been
      associated with inhibition of Ca2+ current in glomus cells. The purpose of the
      present study was to elucidate the characteristics and mechanism of NE inhibition
      of whole cell Ca2+ current isolated from rabbit CB glomus cells and to determine
      the type(s) of Ca2+ channel involved. NE (10 microM) inhibited 24 +/- 2% (SE) of
      the macroscopic Ca2+ current measured at the end of a 25 ms pulse to 0 mV and
      slowed activation of the current. The alpha2 adrenergic receptor antagonist, SK&F
      86466, attenuated these effects. Inhibition by NE was fast and voltage-dependent
      i.e., maximal at -10 mV and then diminished with stronger depolarizations. This
      is characteristic of G protein betagamma subunit interaction with the alpha1
      subunit of certain Ca2+ channels, which can be relieved by depolarizing steps. A
      depolarizing step (30 ms to +80 mV) significantly increased (14 +/- 1%) current
      in the presence of NE, whereas it had no effect before application of NE (1 +/-
      1%). To further test for the involvement of G proteins, NE was applied to cells
      where intracellular GTP was replaced by GDP-betaS. NE had little or no effect on
      Ca2+ current in cells dialyzed with GDP-betaS. To determine whether NE was
      inhibiting N- and/or P/Q-type channels, we applied NE in the presence of omega
      conotoxin MVIIC (MVIIC). In the presence of 2.5 microM MVIIC, NE was equally
      potent at inhibiting the Ca2+ current (23 +/- 4% vs. 23 +/- 4% in control),
      suggesting that NE was not exclusively inhibiting N- or P/Q-type channels. NE was
      also equally potent (30 +/- 2% vs. 26 +/- 4% in control) at inhibiting the Ca2+
      current in the presence of 2 microM nisoldipine, suggesting that NE was not
      inhibiting L-type channels. Further, NE inhibited a significantly larger
      proportion (47 +/- 6%) of the resistant Ca2+ current remaining in the presence of
      NISO and MVIIC. These results suggest that NE inhibition of Ca2+ current in
      rabbit CB glomus cells is mediated in most part by effects on the resistant, non
      L-, N-, or P/Q-type channel and involves a direct G protein betagamma interaction
      with this channel.

PMID- 9914284
TI  - Ionic mechanisms of action of neurotensin in acutely dissociated neurons from the
      diagonal band of Broca of the rat.
AB  - Whole cell recordings were performed on acutely dissociated neurons from the
      horizontal limb of the diagonal band of Broca (hDBB) from rats to elucidate the
      ionic mechanisms of action of neurotensin. Neurotensin caused a decrease in whole
      cell voltage-activated outward currents and failed to elicit a response when Ca2+
      influx was blocked by changing the external solution to the one containing 0 mM
      Ca2+ and 50 microM Cd2+, suggesting the involvement of Ca2+-dependent
      conductances. Charybdotoxin, a specific blocker of voltage-sensitive calcium
      activated K+ channels (IC), caused a decrease in outward currents comparable with
      that caused by blocking calcium influx and occluded the neurotensin-induced
      decrease in outward currents. Similarly, 50 microM tetraethylammonium ions also
      blocked the neurotensin response. Also neurotensin reduced whole cell barium
      currents (IBa) and calcium currents (ICa). Amiloride and omega-conotoxin GVIA,
      but not nimodipine, were able to eliminate the neurotensin-induced decrease in
      IBa. Thus T- and N- but not L-type calcium channels are subject to modulation by
      neurotensin, and this may account for its effects on IC. The predicted changes in
      action potential as a result of the blockade of currents through calcium channels
      culminating into changes in IC were confirmed in the bridge current-clamp
      recordings. Specifically, neurotensin application led to depolarization of the
      resting membrane potential, broadening of spike and a decrease in
      afterhyperpolarization and accommodation. These alterations in action potential
      characteristics that resulted in increased firing rate and excitability of the
      hDBB neurons also were produced by application of charybdotoxin. Neurotensin
      effects on these properties were occluded by 2 - [(1 - 7 - chloro - 4 -
      quinolinyl) - 5 - (2, 6 - di - methoxyphenyl) pyrazol-3-yl) carbonylamino]
      tricyclo (3.3.1.1.)decan-2-carboxylic acid, a nonpeptide high-affinity
      neurotensin receptor antagonist. Neurotensin blockade of IC, possibly through
      ICa, is a potential physiological mechanism whereby this peptide may evoke
      alterations in the cortical arousal, sleep-wake cycle, and theta rhythm.

PMID- 9914285
TI  - A1 adenosine receptors modulate respiratory activity of the neonatal mouse via
      the cAMP-mediated signaling pathway.
AB  - The effects of adenosine and its analogs on the function of the respiratory
      center were studied in the spontaneously active rhythmic slice of neonatal and
      juvenile mice (4-14 days old). Whole cell, spontaneous postsynaptic currents
      (sPSCs) and single channel KATP currents were recorded in inspiratory neurons of
      the pre-Botzinger complex. Adenosine (50-600 microM) inhibited the respiratory
      rhythm. This was accompanied by increase in the activity of KATP channels in cell
      attached patches. The A1 adenosine receptor agonist, 2-chloro-N6
      cyclopentyladenosine (CCPA, 0.3-2 microM), inhibited the respiratory rhythm,
      sPSCs, and enhanced activity of KATP channels. The A1 adenosine receptor
      antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 1-3 microM), showed
      opposite effects and occluded the CCPA actions. Agents specific for A2 adenosine
      receptors (CGS 21860 and NECA, both applied at 1-10 microM) were without effect.
      Elevation of intracellular cAMP concentration ([cAMP]i) by 8-Br-cAMP (200-500
      microM), forskolin (0.5-2 microM), or isobutylmethylxantine (IBMX, 30-90 microM)
      reinforced the rhythm, whereas NaF (100-800 microM) depressed it. The open
      probability of single KATP channels in cell-attached patches decreased after
      application of forskolin and increased in the presence of NaF. [cAMP]i elevation
      reversed the effects of A1 receptors both on the respiratory rhythm and KATP
      channels. A1 receptors and [cAMP]i modified the hypoxic respiratory response. In
      the presence of A1 agonists the duration of hypoxic augmentation shortened, and
      depression of the respiratory rhythm occurred earlier. Elevation of [cAMP]i
      prolonged augmentation and delayed the development of the depression. We conclude
      that A1 adenosine receptors modulate the respiratory rhythm via inhibition of
      intracellular cAMP production and concomitant activation of KATP channels.

PMID- 9914286
TI  - Complex spike activity of Purkinje cells in the ventral uvula and nodulus of
      pigeons in response to translational optic flow.
AB  - The complex spike (CS) activity of Purkinje cells in the ventral uvula and
      nodulus of the vestibulocerebellum was recorded from anesthetized pigeons in
      response to translational optic flow. Translational optic flow was produced using
      a "translator" projector: a mechanical device that projected a translational
      optic flowfield onto the walls, ceiling, and floor of the room and encompassed
      the entire binocular visual field. CS activity was broadly tuned but maximally
      modulated in response to translational optic flow along a "best" axis. Each
      neuron was assigned a vector representing the direction in which the animal would
      need to translate to produce the optic flowfield that resulted in maximal
      excitation. The vector is described with reference to a standard right-handed
      coordinate system, where the vectors, +x, +y, and +z represent, rightward,
      upward, and forward translation of the animal, respectively. Neurons could be
      grouped into four response types based on the vector of maximal excitation. +y
      neurons were modulated maximally in response to a translational optic flowfield
      that results from self-motion upward along the vertical (y) axis. -y neurons also
      responded best to translational optic flow along the vertical axis but showed the
      opposite direction preference. The two remaining groups responded best to
      translational optic flow along horizontal axes: -x + z neurons and -x-z neurons.
      In summary, our results suggest that the olivocerebellar system dedicated to the
      analysis of translational optic flow is organized according to a reference frame
      consisting of three approximately orthogonal axes: the vertical axis, and two
      horizontal axes oriented 45 degrees to either side the midline. Previous research
      has shown that the rotational optic flow system, the eye muscles, the vestibular
      semicircular canals and the postural control system all share a similar spatial
      frame of reference.

PMID- 9914287
TI  - Responses of neurons in the nucleus of the basal optic root to translational and
      rotational flowfields.
AB  - The nucleus of the basal optic root (nBOR) receives direct input from the
      contralateral retina and is the first step in a pathway dedicated to the analysis
      of optic flowfields resulting from self-motion. Previous studies have shown that
      most nBOR neurons exhibit direction selectivity in response to large-field
      stimuli moving in the contralateral hemifield, but a subpopulation of nBOR
      neurons has binocular receptive fields. In this study, the activity of binocular
      nBOR neurons was recorded in anesthetized pigeons in response to panoramic
      translational and rotational optic flow. Translational optic flow was produced by
      the "translator" projector described in the companion paper, and rotational optic
      flow was produced by a "planetarium projector" described by Wylie and Frost. The
      axis of rotation or translation could be positioned to any orientation in three
      dimensional space. We recorded from 37 cells, most of which exhibited a strong
      contralateral dominance. Most of these cells were located in the caudal and
      dorsal aspects of the nBOR complex and many were localized to the subnucleus nBOR
      dorsalis. Other units were located outside the boundaries of the nBOR complex in
      the adjacent area ventralis of Tsai or mesencephalic reticular formation. Six
      cells responded best to rotational flowfields, whereas 31 responded best to
      translational flowfields. Of the rotation cells, three preferred rotation about
      the vertical axis and three preferred horizontal axes. Of the translation cells,
      3 responded best to a flowfield simulating downward translation of the bird along
      a vertical axis, whereas the remaining 28 responded best to flowfields resulting
      from translation along axes in the horizontal plane. Seventeen of these cells
      preferred a flowfield resulting from the animal translating backward along an
      axis oriented approximately 45 degrees to the midline, but the best axes of the
      remaining eleven cells were distributed throughout the horizontal plane with no
      definitive clustering. These data are compared with the responses of
      vestibulocerebellar Purkinje cells.

PMID- 9914288
TI  - Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy
      fiber-granule cell transmission in rat cerebellum.
AB  - Long-term potentiation (LTP) is a form of synaptic plasticity that can be
      revealed at numerous hippocampal and neocortical synapses following high
      frequency activation of N-methyl--aspartate (NMDA) receptors. However, it was not
      known whether LTP could be induced at the mossy fiber-granule cell relay of
      cerebellum. This is a particularly interesting issue because theories of the
      cerebellum do not consider or even explicitly negate the existence of mossy fiber
      granule cell synaptic plasticity. Here we show that high-frequency mossy fiber
      stimulation paired with granule cell membrane depolarization (-40 mV) leads to
      LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a
      relatively hyperpolarized potential (-60 mV) or in the presence of NMDA receptor
      blockers [5-amino--phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl
      Kyn)] prevented LTP, suggesting that the induction process involves a voltage
      dependent NMDA receptor activation. Metabotropic glutamate receptors were also
      involved because blocking them with (+)-alpha-methyl-4-carboxyphenyl-glycine
      (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation
      required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was
      expressed through an increase in both the NMDA and non-NMDA receptor-mediated
      current and by an NMDA current slowdown, suggesting that complex mechanisms
      control synaptic efficacy during LTP. LTP at the mossy fiber-granule cell synapse
      provides the cerebellar network with a large reservoir for memory storage, which
      may be needed to optimize pattern recognition and, ultimately, cerebellar
      learning and computation.

PMID- 9914289
TI  - Modulation of transmitter release by action potential duration at the hippocampal
      CA3-CA1 synapse.
AB  - Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers
      neurotransmitter release. Action potential duration plays a determinant role in
      the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+
      influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The
      effect of action potential duration on Ca2+ influx and transmitter release was
      investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to
      broaden the action potential and thereby increase presynaptic Ca2+ influx. This
      increase of Ca2+ influx appeared to be much less effective in enhancing
      transmitter release than raising the extracellular Ca2+ concentration. 4-AP did
      not change the Ca2+ dependence of transmitter release but instead shifted the
      synaptic transmission curve toward larger total Ca2+ influx. These results
      suggest that changing the duration of Ca2+ influx is not equivalent to changing
      its amplitude in locally building up an effective Ca2+ concentration near the
      Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N
      type Ca2+ channel blocker omegaCgTx GVIA was much less effective in blocking
      transmitter release. This phenomenon was not simply due to a saturation of the
      release machinery by the increased overall Ca2+ influx because a similar
      reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker
      Cd2+ resulted in much more inhibition of transmitter release. Rather, the
      different potencies of omega-CgTx GVIA and Cd2+ in inhibiting transmitter release
      suggest that the Ca2+ sensor is possibly located at a distance from a cluster of
      Ca2+ channels such that it is sensitive to the location of Ca2+ channels within
      the cluster.

PMID- 9914290
TI  - Reduced voltage-dependent Ca2+ signaling in CA1 neurons after brief ischemia in
      gerbils.
AB  - An initial overload of intracellular Ca2+ plays a critical role in the delayed
      death of hippocampal CA1 neurons that die a few days after transient ischemia.
      Without direct evidence, the prevailing hypothesis has been that Ca2+ overload
      may recur until cell death. Here, we report the first measurements of
      intracellular Ca2+ in living CA1 neurons within brain slices prepared 1, 2, and 3
      days after transient (5 min) ischemia. With no sign of ongoing Ca2+ overload,
      voltage-dependent Ca2+ transients were actually reduced after 2-3 days of
      reperfusion. Resting Ca2+ levels and recovery rate after loading were similar to
      neurons receiving no ischemic insult. The tetrodotoxin-insensitive Ca spike,
      normally generated by these neurons, was absent at 2 days postischemia, as was a
      large fraction of Ca2+-dependent spike train adaptation. These surprising
      findings may lead to a new perspective on delayed neuronal death and
      intervention.

PMID- 9914291
TI  - Ionic mechanisms underlying depolarizing responses of an identified insect motor
      neuron to short periods of hypoxia.
AB  - Hypoxia can dramatically disrupt neural processing because energy-dependent
      homeostatic mechanisms are necessary to support normal neuronal function. In a
      human context, the long-term effects of such disruption may become all too
      apparent after a "stroke," in which blood-flow to part of the brain is
      compromised. We used an insect preparation to investigate the effects of hypoxia
      on neuron membrane properties. The preparation is particularly suitable for such
      studies because insects respond rapidly to hypoxia, but can recover when they are
      restored to normoxic conditions, whereas many of their neurons are large,
      identifiable, and robust. Experiments were performed on the "fast" coxal
      depressor motoneuron (Df) of cockroach (Periplaneta americana). Five-minute
      periods of hypoxia caused reversible multiphasic depolarizations (10-25 mV; n =
      88), consisting of an initial transient depolarization followed by a partial
      repolarization and then a slower phase of further depolarization. During the
      initial depolarizing phase, spontaneous plateau potentials normally occurred, and
      inhibitory postsynaptic potential frequency increased considerably; 2-3 min after
      the onset of hypoxia all electrical activity ceased and membrane resistance was
      depressed. On reoxygenation, the membrane potential began to repolarize almost
      immediately, becoming briefly more negative than the normal resting potential.
      All phases of the hypoxia response declined with repeated periods of hypoxia.
      Blockade of ATP-dependent Na/K pump by 30 microM ouabain suppressed only the
      initial transient depolarization and the reoxygenation-induced hyperpolarization.
      Reduction of aerobic metabolism between hypoxic periods (produced by bubbling air
      through the chamber instead of oxygen) had a similar effect to that of ouabain.
      Although the depolarization seen during hypoxia was not reduced by tetrodotoxin
      (TTX; 2 microM), lowering extracellular Na+ concentration or addition of 500
      microM Cd2+ greatly reduced all phases of the hypoxia-induced response,
      suggesting that Na influx occurs through a TTX-insensitive Cd2+-sensitive
      channel. Exposure to 20 mM tetraethylammonium and 1 mM 3,4-diaminopyridine
      increased the amplitude of the hypoxia-induced depolarization, suggesting that
      activation of K channels may normally limit the amplitude of the hypoxia
      response. In conclusion we suggest that the slow hypoxia-induced depolarization
      on motoneuron Df is mainly carried by a TTX-resistant, Cd2+-sensitive sodium
      influx. Ca2+ entry may also make a direct or indirect contribution to the hypoxia
      response. The fast transient depolarization appears to result from block of the
      Na/K pump, whereas the reoxygenation-induced hyperpolarization is largely caused
      by its subsequent reactivation.

PMID- 9914292
TI  - Step-tracking movements of the wrist. IV. Muscle activity associated with
      movements in different directions.
AB  - We examined the patterns of muscle activity associated with multiple directions
      of step-tracking movements of the wrist in humans and monkeys. Human subjects
      made wrist movements to 12 different targets that required varying amounts of
      flexion-extension and radial-ulnar deviation. Wrist muscles displayed two
      patterns of electromyographic (EMG) modulation as movement direction changed:
      amplitude graded and temporally shifted. The amplitude-graded pattern was
      characterized by modulation of the quantity of muscle activity that occurred
      during two distinct time periods, an agonist burst interval that began before
      movement onset and an antagonist burst interval that began just after movement
      onset. The timing of muscle activity over the two intervals showed little
      variation with changes in movement direction. For some directions of movement,
      EMG activity was present over both time intervals, resulting in "double bursts."
      Modulation of activity during the agonist burst interval was particularly
      systematic and was well fit by a cosine function. In contrast, the temporally
      shifted pattern was characterized by a gradual change in the timing of a single
      burst of muscle activity. The burst occurred at a time intermediate between the
      agonist and antagonist burst intervals. The temporally shifted pattern was seen
      less frequently than the amplitude-graded pattern and was present only in
      selected wrist muscles for specific directions of movement. Monkeys made wrist
      movements to 8-16 different targets that required varying amounts of flexion
      extension and radial-ulnar deviation. These movements were performed more slowly
      than those of human subjects. The wrist muscles of the monkeys we examined
      displayed the amplitude-graded pattern of activity but not the temporally shifted
      pattern. Stimulation of individual wrist muscles in monkeys resulted in wrist
      movements that were markedly curved, particularly for the wrist extensors. These
      results indicate that step-tracking movements of the wrist are generated mainly
      by using the amplitude-graded pattern to modulate muscle activity. We propose
      that this pattern reflects a central process that decomposes an intended movement
      into an agonist, "propulsive" component and an antagonist, "braking" component.
      Separate bursts of muscle activity then are generated to control each component.
      On the other hand, we argue that the temporally shifted pattern may function to
      reduce the amount of movement curvature associated with the activation of wrist
      muscles.

PMID- 9914293
TI  - Mapping membrane potential transients in crayfish (Procambarus clarkii) optic
      lobe neuropils with voltage-sensitive dyes.
AB  - Voltage-sensitive dyes NK 2761 and RH 155 were employed (in conjunction with a 12
      x 12 photodiode array) to study membrane potential transients in optic lobe
      neuropils in the eye stalk of the crayfish Procambarus clarkii. By this means we
      investigated a pathway linking deutocerebral projection neurons, via
      hemiellipsoid body local interneurons, to an unidentified target (most likely
      neurons processing visual information) in the medulla terminalis. Rapid (10- to
      20-ms duration), transient changes in absorption with the characteristics of
      action potentials were recorded from the optic nerve and the region occupied by
      deutocerebral projection neurons after stimulation of the olfactory globular
      tract in the optic nerve and were blocked by 1 microM tetrodotoxin. Action
      potentials appeared to propagate to the glomerular layer of the hemiellipsoid
      body where synaptic responses were recorded from a restricted region of the
      hemiellipsoid body occupied by dendrites of hemiellipsoid body neurons. Action
      potentials were also recorded from processes of hemiellipsoid body neurons
      located in the medulla terminalis. Synaptic responses in the hemiellipsoid body
      and medulla terminalis were eliminated by addition to the saline of 500 microM
      Cd2+ or 20 mM Co2+, whereas the action potential attributed to branches of
      deutocerebral projection neurons in the hemiellipsoid body remained unaffected.
      Action potentials of hemiellipsoid body neurons in the medulla terminalis evoked
      postsynaptic potentials (50- to 200-ms duration) with an unidentified target in
      the medulla terminalis. Transient absorption signals were not detected in either
      the internal or external medulla nor were they recorded from other parts of the
      optic lobes in response to electrical stimulation of axons of the deutocerebral
      projection neurons. Functional maps of optical activity, together with
      electrophysiological and pharmacological findings, suggest that gamma
      aminobutyric acid affects synaptic transmission in glomeruli of the hemiellipsoid
      body. Synapses of the olfactory pathway located in the medulla terminalis may act
      as a "filter," modifying visual information processing during olfactory
      stimulation.

PMID- 9914294
TI  - Synaptic organization and neurotransmitters in the rat accessory olfactory bulb.
AB  - The accessory olfactory bulb (AOB) is the first relay station in the vomeronasal
      system and may play a critical role in processing pheromone signals. The AOB
      shows similar but less distinct lamination compared with the main olfactory bulb
      (MOB). In this study, synaptic organization of the AOB was analyzed in slice
      preparations from adult rats by using both field potential and patch-clamp
      recordings. Stimulation of the vomeronasal nerve (VN) evoked field potentials
      that showed characteristic patterns in different layers of the AOB. Current
      source density (CSD) analysis of the field potentials revealed spatiotemporally
      separated loci of inward current (sinks) that represented sequential activation
      of different neuronal components: VN activity (period I), synaptic excitation of
      mitral cell apical dendrites (period II), and activation of granule cells by
      mitral cell basal dendrites (period III). Stimulation of the lateral olfactory
      tract also evoked field potentials in the AOB, which indicated antidromic
      activation of the mitral cells (period I and II) followed by activation of
      granule cells (period III). Whole cell patch recordings from mitral and granule
      cells of the AOB supported that mitral cells are excited by VN terminals and
      subsequently activate granule cells through dendrodendritic synapses. Both CSD
      analysis and patch recordings provided evidence that glutamate is the
      neurotransmitter at the vomeronasal receptor neuron; mitral cell synapses and
      both NMDA and non-NMDA receptors are involved. We also demonstrated
      electrophysiologically that reciprocal interaction between mitral and granule
      cells in the AOB is through the dendrodendritic reciprocal synapses. The
      neurotransmitter at the mitral-to-granule synapses is glutamate and at the
      granule-to-mitral synapse is gamma-aminobutyric acid. The synaptic interactions
      among receptor cell terminals, mitral cells, and granule cells in the AOB are
      therefore similar to those in the MOB, suggesting that processing of chemosensory
      information in the AOB shares similarities with that in the MOB.

PMID- 9914295
TI  - Visible evidence for differences in synaptic effectiveness with activity
      dependent vesicular uptake and release of FM1-43.
AB  - Activity-dependent uptake and release of the fluorescent probe FM1-43 were used
      to compare synaptic performance (rates of transmitter release and synaptic
      vesicle turnover) at different frequencies in phasic and tonic motor neurons
      innervating the crayfish leg extensor muscle and in the tonic motor neuron of the
      opener muscle. The phasic extensor motor neuron, which has a high quantal content
      of transmitter release, accumulated and released FM1-43 more rapidly than the
      tonic motor neuron, especially at low frequencies of stimulation. Individual
      bright spots appeared on the varicosities of the junctional terminals during
      stimulation in FM1-43; these spots corresponded to zones of immunostaining for
      the synaptic vesicle associated protein synaptotagmin, but they were larger and
      less numerous than synapses identified by electron microscopy and appear to
      represent one to several synapses with their associated clusters of synaptic
      vesicles. The number of bright spots observed on varicosities of the tonic
      terminal after stimulation at >/=20 Hz is generally similar to values for
      responding units (n) calculated from binomial distributions derived from quantal
      analysis. At frequencies of </=10 Hz, bright spots did not usually appear on
      tonic extensor varicosities, and the quantal release patterns were best fitted
      with Poisson distributions. Another tonic motor neuron, the excitor of the opener
      muscle, showed individual bright spots at lower frequencies of stimulation,
      consistent with its higher quantal output at these frequencies and corresponding
      with the binomial fits for quantal release distributions. In this axon, the
      number of distinctive bright spots increased with frequency in the 2- to 20-Hz
      range, indicating increased participation of synapses during frequency
      facilitation. In the tonic extensor neuron terminals, the brightness and the size
      of the individual spots increased with frequency, and new foci of dye uptake
      appeared at the edges of preexisting spots. Relative intensity change varied
      considerably among individual spots during dye loading at different frequencies.
      Similarly, individual spots on a single tonic terminal destained at different
      rates when stimulated after previous loading with FM1-43. These results suggest
      differential performance of individual synapses or small groups of synapses, some
      being more effective in transmitter release than others, as inferred from
      previous ultrastructural and quantal analysis studies. The large overall
      differences between phasic and tonic synapses suggest differential regulation of
      transmitter release at individual synapses in the two neurons.

PMID- 9914296
TI  - Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in
      hippocampal stratum oriens/alveus interneurons.
AB  - Metabotropic glutamate receptors (mGluRs) are expressed heterogeneously in
      hippocampal interneurons, and their signal transduction cascades remain largely
      unclear. We characterized an oscillatory response activated by the mGluR agonist
      1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in hippocampal
      interneurons of stratum oriens-alveus (OA) with simultaneous whole cell current
      clamp recordings and intracellular Ca2+ imaging with confocal microscopy. 1S,3R
      ACPD induced oscillatory membrane depolarizations and rises in intracellular Ca2+
      that persisted in tetrodotoxin and were blocked by the antagonist of group I and
      II mGluRs (S)-alpha-methyl-4-carboxyphenylglycine. Membrane depolarizations and
      intracellular Ca2+ rises were blocked by extracellular Cd2+ and in Ca2+-free
      medium. mGluR responses therefore required Ca2+ influx via voltage-gated Ca2+
      channels. 1S, 3R-ACPD responses were also antagonized by depleting intracellular
      stores with thapsigargin and ryanodine, indicating that Ca2+ release from
      intracellular stores was also necessary. These data suggest that oscillatory
      responses generated by group I/II mGluRs involve a coupling of Ca2+ entry through
      voltage-gated Ca2+ channels and Ca2+ release from internal stores. In contrast,
      1S,3R-ACPD evoked only smaller depolarizations and intracellular Ca2+ rises, with
      no oscillations, in other hippocampal interneurons located in or near stratum
      lacunosum-moleculare. Thus mGluR-mediated oscillatory responses are specifically
      expressed in certain interneuron subtypes. This heterogeneous expression of
      glutamate and Ca2+ signaling pathways in specific interneurons may be relevant to
      their selective vulnerability to excitotoxicity.

PMID- 9914298
TI  - Recovery of fMRI activation in motion area MT following storage of the motion
      aftereffect.
AB  - We used functional magnetic resonance imaging (fMRI) during storage of the motion
      aftereffect (MAE) to examine the relationship between motion perception and
      neural activity in the human cortical motion complex MT+ (including area MT and
      adjacent motion-selective cortex). MT+ responds not only to physical motion but
      also to illusory motion, as in the MAE when subjects who have adapted to
      continuous motion report that a subsequent stationary test stimulus appears to
      move in the opposite direction. In the phenomenon of storage, the total decay
      time of the MAE is extended by inserting a dark period between adaptation and
      test phases. That is, when the static test pattern is presented after a storage
      period equal in duration to the normal MAE, the illusory motion reappears for
      almost as long as the original effect despite the delay. We examined fMRI
      activation in MT+ during and after storage. Seven subjects viewed continuous
      motion, followed either by an undelayed stationary test (immediate MAE) or by a
      completely dark storage interval preceding the test (stored MAE). Like the
      perceptual effect, activity in MT+ dropped during the storage interval then
      rebounded to reach a level much higher than after the same delay without storage.
      Although MT+ activity was slightly enhanced during the storage period following
      adaptation to continuous motion (compared with a control sequence in which the
      adaptation grating oscillated and no MAE was perceived), this enhancement was
      much less than that observed during the perceptual phenomenon. These results
      indicate that following adaptation, activity in MT+ is pronounced only with the
      presentation of an appropriate visual stimulus, during which the MAE is
      perceived.

PMID- 9914297
TI  - Activation of distinct motor cortex regions during ipsilateral and contralateral
      finger movements.
AB  - Previous studies have shown that unilateral finger movements are normally
      accompanied by a small activation in ipsilateral motor cortex. The magnitude of
      this activation has been shown to be altered in a number of conditions,
      particularly in association with stroke recovery. The site of this activation,
      however, has received limited attention. To address this question, functional
      magnetic resonance imaging (MRI) was used to study precentral gyrus activation in
      six control and three stroke patients during right index finger tapping, then
      during left index finger tapping. In each hemisphere, the most significantly
      activated site (P < 0.001 required) was identified during ipsilateral and during
      contralateral finger tapping. In the motor cortex of each hemisphere, the site
      activated during use of the ipsilateral hand differed from that found during use
      of the contralateral hand. Among the 11 control hemispheres showing significant
      activation during both motor tasks, the site for ipsilateral hand representation
      (relative to contralateral hand site in the same hemisphere) was significantly
      shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11
      hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6
      of 11 hemispheres, tapping of the contralateral finger simultaneously activated
      both the ipsilateral and the contralateral finger sites, suggesting bilateral
      motor control by the ipsilateral finger site. The sites activated during
      ipsilateral and contralateral hand movement showed similar differences in the
      unaffected hemisphere of stroke patients. The region of motor cortex activated
      during ipsilateral hand movements is spatially distinct from that identified
      during contralateral hand movements.

PMID- 9914299
TI  - Oculomotor control of primary eye position discriminates between translation and
      tilt.
AB  - We have previously shown that fast phase axis orientation and primary eye
      position in rhesus monkeys are dynamically controlled by otolith signals during
      head rotations that involve a reorientation of the head relative to gravity.
      Because of the inherent ambiguity associated with primary otolith afferent coding
      of linear accelerations during head translation and tilts, a similar organization
      might also underlie the vestibulo-ocular reflex (VOR) during translation. The
      ability of the oculomotor system to correctly distinguish translational
      accelerations from gravity in the dynamic control of primary eye position has
      been investigated here by comparing the eye movements elicited by sinusoidal
      lateral and fore-aft oscillations (0.5 Hz +/- 40 cm, equivalent to +/- 0.4 g)
      with those during yaw rotations (180 degrees/s) about a vertically tilted axis
      (23.6 degrees). We found a significant modulation of primary eye position as a
      function of linear acceleration (gravity) during rotation but not during lateral
      and fore-aft translation. This modulation was enhanced during the initial phase
      of rotation when there was concomitant semicircular canal input. These findings
      suggest that control of primary eye position and fast phase axis orientation in
      the VOR are based on central vestibular mechanisms that discriminate between
      gravity and translational head acceleration.

PMID- 9914300
TI  - A relative energy failure is associated with low-Mg2+ but not with 4
      aminopyridine induced seizure-like events in entorhinal cortex.
AB  - During seizure-like events (SLEs), intracellular Ca2+ concentration ([Ca2+]i)
      increases causing depolarization of the mitochondrial membrane and subsequent
      intramitochondrial accumulation of Ca2+. Mitochondrial depolarization results in
      an interruption of oxidative phosphorylation and increase in reactive oxygen
      species. Calcium activates enzymes of the citrate cycle. A characteristic feature
      of the low-Mg2+-induced SLEs is that they are transformed to a late activity
      refractory to anticonvulsant drugs, which may be regarded as a model system of
      difficult to treat status epilepticus. In contrast, 4-aminopyridine (4-AP)
      induced activity rarely evolves to such late activity. The autofluorescence of
      NAD(P)H was used to monitor changes in cellular energy metabolism in the
      entorhinal cortex in two in vitro models of focal epilepsy. During repetitive 4
      AP-induced SLEs there was a short decrease followed by a long-lasting overshoot
      of the NAD(P)H signal. This sequence remained unaltered during recurring SLEs. In
      contrast, during recurrent low-Mg2+-induced SLEs, the brief initial NADH signal
      reduction was unchanged but the following overshoot of NADH displayed a
      continuous decrease. This indicates a relative energy failure, which may
      contribute to the transformation to late activity in the low-Mg2+ model.

PMID- 9914301
TI  - Reduction of zolpidem sensitivity in a freeze lesion model of neocortical
      dysgenesis.
AB  - Early postnatal freeze lesions in rat neocortex produce anatomic abnormalities
      resembling those observed in human patients with seizure disorders. Although in
      vitro brain slices containing the lesion are hyperexcitable, the mechanisms of
      this alteration have yet to be elucidated. To test the hypothesis that changes in
      postsynaptic inhibitory receptors may underlie this hyperexcitability, we
      examined properties of gamma-aminobutyric acid type A receptor (GABAAR)-mediated
      miniature inhibitory postsynaptic currents (mIPSCs). Recordings were obtained in
      layer II/III pyramidal cells located 1-2 mm lateral to the lesion. mIPSC peak
      amplitude and rate of rise were increased relative to nonlesioned animals,
      whereas decay time constant and interevent interval were unaltered. Bath
      application of zolpidem at a concentration (20 nM) specific for activation of the
      type 1 benzodiazepine receptor had no significant effect on decay time constant
      in six of nine cells. Exposure to higher concentrations (100 nM) enhanced the
      decay time constant of all cells tested (n = 7). Because mIPSCs from unlesioned
      animals were sensitive to both concentrations of zolpidem, these results suggest
      that freeze lesions may decrease the affinity of pyramidal cell GABAARs for
      zolpidem. This could be mediated via a change in alpha-subunit composition of the
      GABAAR, which eliminates the type 1 benzodiazepine receptor.

PMID- 9914302
TI  - Neuromodulation of dendritic action potentials.
AB  - The extent to which regenerative action potentials invade hippocampal CA1
      pyramidal dendrites is dependent on both recent activity and distance from the
      soma. Previously, we have shown that the amplitude of back-propagating dendritic
      action potentials can be increased by activating either protein kinase A (PKA) or
      protein kinase C (PKC) and a subsequent depolarizing shift in the activation
      curve for dendritic K+ channels. Physiologically, an increase in intracellular
      PKA and PKC would be expected upon activation of beta-adrenergic and muscarinic
      acetylcholine receptors, respectively. Accordingly, we report here that
      activation of either of these neurotransmitter systems results in an increase in
      dendritic action-potential amplitude. Activation of the dopaminergic
      neurotransmitter system, which is also expected to raise intracellular adenosine
      3',5'-cyclic monophosphate (cAMP) and PKA levels, increased action-potential
      amplitude in only a subpopulation of neurons tested.

PMID- 9914303
TI  - A sensitive, viable-colony staining method using Nile red for direct screening of
      bacteria that accumulate polyhydroxyalkanoic acids and other lipid storage
      compounds.
AB  - The oxazine dye Nile blue A and its fluorescent oxazone form, Nile red, were used
      to develop a simple and highly sensitive staining method to detect poly(3
      hydroxybutyric acid) and other polyhydroxyalkanoic acids (PHAs) directly in
      growing bacterial colonies. In contrast to previously described methods, these
      dyes were directly included in the medium at concentrations of only 0.5
      microgram/ml, and growth of the cells occurred in the presence of the dyes. This
      allowed an estimation of the presence of PHAs in viable colonies at any time
      during the growth experiment and a powerful discrimination between PHA-negative
      and PHA-positive strains. The presence of Nile red or Nile blue A did not affect
      growth of the bacteria. This viable-colony staining method was in particular
      applicable to gram-negative bacteria such as Azotobacter vinelandii, Escherichia
      coli, Pseudomonas putida, and Ralstonia eutropha. It was less suitable for
      discriminating between PHA-negative and PHA-positive strains of gram-positive
      bacteria such as Bacillus megaterium or Rhodococcus ruber, but it could also be
      used to discriminate between wax-ester- and triacylglycerol-negative and 
      positive strains of Acinetobacter calcoaceticus or Rhodococcus opacus. The
      potential of this new method and its application to further investigations of PHA
      synthases and PHA biosynthesis pathways are discussed.

PMID- 9914304
TI  - Anaerobic transformation of quercetin-3-glucoside by bacteria from the human
      intestinal tract.
AB  - From human feces two phenotypically different types of bacteria were isolated on
      quercetin-3-glucoside as carbon and energy source. Isolates of one type were
      identified as strains of Enterococcus casseliflavus. They utilized the sugar
      moiety of the glycoside, but did not degrade the aglycon further. The sugar
      moiety (4 mM) was fermented to 5.5 +/- 2.1 mM formate, 2.1 +/- 0.7 mM acetate,
      1.6 +/- 0.3 mM l-lactate, and 1.3 +/- 0.4 mM ethanol. The second type of isolate
      was identified as Eubacterium ramulus. This organism was capable of degrading the
      aromatic ring system. Growing cultures of Eubacterium ramulus converted 5 mM
      quercetin-3-glucoside to 1.7 +/- 0.6 mM 3,4-dihydroxyphenylacetic acid, 7.6 +/-
      1.0 mM acetate, and 4.0 +/- 0.4 mM butyrate. Molecular hydrogen, 3,4
      dihydroxybenzaldehyde, and ethanol were detected in small amounts. Phloroglucinol
      was a transient intermediate in the breakdown of quercetin-3-glucoside.
      Eubacterium ramulus did not grow on the aglycon quercetin or the ring-fission
      intermediate phloroglucinol, but cleaved the flavonoid ring system when glucose
      was present as a cosubstrate. The most probable number of quercetin-3-glucoside
      degrading bacteria determined in nine human fecal samples was 10(7)-10(9)/g dry
      mass. Isolates from these experiments were all identified as Eubacterium ramulus.

PMID- 9914305
TI  - Characterization of the Escherichia coli CcmH protein reveals new insights into
      the redox pathway required for cytochrome c maturation.
AB  - The CcmH protein of Escherichia coli is encoded by the last gene of the ccm gene
      cluster required for cytochrome c maturation. A mutant in which the entire ccmH
      gene was deleted failed to synthesize both indigenous and foreign c-type
      cytochromes. However, deletion of the C-terminal hydrophilic domain homologous to
      CycH of other gram-negative bacteria affected neither the biogenesis of
      indigenous c-type cytochromes nor that of the Bradyrhizobium japonicum cytochrome
      c550. This confirmed that only the N-terminal domain containing a conserved CXXC
      motif is required in E. coli. PhoA fusion analysis showed that this domain is
      periplasmic. Site-directed mutagenesis of the cysteines of the CXXC motif
      revealed that both cysteines are required for cytochrome c maturation during
      aerobic growth, whereas only the second cysteine is required for cytochrome c
      maturation during anaerobic growth. The deficiency of the point mutants was
      complemented when 2-mercapto-ethanesulfonic acid was added to growing cells;
      other thiol compounds did not stimulate cytochrome c formation in these strains.
      We propose a model for the reaction sequence in which CcmH keeps the heme binding
      site of apocytochrome c in a reduced form for subsequent heme ligation.

PMID- 9914306
TI  - Glucosylglycerol-phosphate synthase: target for ion-mediated regulation of
      osmolyte synthesis in the cyanobacterium synechocystis sp. strain PCC 6803 
AB  - The response of cyanobacteria to a changing osmotic environment includes the
      accumulation of organic osmolytes such as glucosylglycerol. The activation of the
      enzymes involved in glucosylglycerol synthesis [glucosylglycerol-phosphate
      synthase (GGPS) and glucosylglycerol-phosphate phosphatase (GGPP)] in
      Synechocystis sp. strain PCC 6803 by various salts and salt concentrations was
      investigated in vitro. GGPS seemed to be the target for salt-mediated regulation
      of glucosylglycerol synthesis in vitro. GGPS activation was dependent on the
      concentration of NaCl, and a sigmoidal plot was obtained. Sensitivity to NaCl was
      markedly enhanced by low Mg+2 concentrations (optimal at 4 mM), but Mg2+ was not
      absolutely necessary for the Na+ stimulation. As in the case of NaCl, other salts
      (including MgCl2) stimulated GGPS. The relative order of GGPS activation in the
      presence of chloride by the cations at constant ionic strength was Li+ > Na+ >
      K+, Mg2+ Mn2+. No absolute dependence on ionic strength was observed in Mg2+/Na+
      exchange experiments. The degree of activation by ions at various concentrations
      was positively related to the increasing destabilizing properties of the cations
      according to the Hofmeister rule, where chaotropic cations are most efficient.
      Cations were responsible for activation since chaotropic anions counteracted the
      activating effect of cations.

PMID- 9914307
TI  - Syntrophus aciditrophicus sp. nov., a new anaerobic bacterium that degrades fatty
      acids and benzoate in syntrophic association with hydrogen-using microorganisms.
AB  - Strain SBT is a new, strictly anaerobic, gram-negative, nonmotile, non
      sporeforming, rod-shaped bacterium that degrades benzoate and certain fatty acids
      in syntrophic association with hydrogen/formate-using microorganisms. Strain SBT
      produced approximately 3 mol of acetate and 0.6 mol of methane per mol of
      benzoate in coculture with Methanospirillum hungatei strain JF1. Saturated fatty
      acids, some unsaturated fatty acids, and methyl esters of butyrate and hexanoate
      also supported growth of strain SBT in coculture with Desulfovibrio strain G11.
      Strain SBT grew in pure culture with crotonate, producing acetate, butyrate,
      caproate, and hydrogen. The molar growth yield was 17 +/- 1 g cell dry mass per
      mol of crotonate. Strain SBT did not grow with fumarate, iron(III), polysulfide,
      or oxyanions of sulfur or nitrogen as electron acceptors with benzoate as the
      electron donor. The DNA base composition of strain SBT was 43.1 mol% G+C.
      Analysis of the 16 S rRNA gene sequence placed strain SBT in the delta
      subdivision of the Proteobacteria, with sulfate-reducing bacteria. Strain SBT was
      most closely related to members of the genus Syntrophus. The clear phenotypic and
      genotypic differences between strain SBT and the two described species in the
      genus Syntrophus justify the formation of a new species, Syntrophus
      aciditrophicus.

PMID- 9914308
TI  - Membrane-bound F420H2-dependent heterodisulfide reduction in methanococcus voltae
AB  - Washed membranes prepared from H2+CO2- or formate-grown cells of Methanococcus
      voltae catalyzed the oxidation of coenzyme F420H2 and the reduction of the
      heterodisulfide (CoB-S-S-CoM) of 2-mercaptoethanesulfonate and 7
      mercaptoheptanoylthreonine phosphate, which is the terminal electron acceptor of
      the methanogenic pathway. The reaction followed a 1:1 stoichiometry according to
      the equation: F420H2 + COB-S-S-CoM --> F420 + CoM-SH + CoB-SH. These findings
      indicate that the reaction depends on a membrane-bound F420H2-oxidizing enzyme
      and on the heterodisulfide reductase, which remains partly membrane-bound after
      cell lysis. To elucidate the nature of the F420H2-oxidizing protein, washed
      membranes were solubilized with detergent, and the enzyme was purified by sucrose
      density centrifugation, anion-exchange chromatography, and gel filtration.
      Several lines of evidence indicate that F420H2 oxidation is catalyzed by a
      membrane-associated F420-reducing hydrogenase. The purified protein catalyzed the
      H2-dependent reduction of methyl viologen and F420. The apparent molecular mass
      and the subunit composition (43, 37, and 27 kDa) are almost identical to those of
      the F420-reducing hydrogenase that has already been purified from Mc. voltae.
      Moreover, the N-terminus of the 37-kDa subunit is identical to the amino acid
      sequence deduced from the fruG gene of the operon encoding the selenium
      containing F420-reducing hydrogenase from Mc. voltae. A distinct F420H2
      dehydrogenase, which is present in methylotrophic methanogens, was not found in
      this organism.

PMID- 9914309
TI  - Integration of minitransposons for expression of the Escherichia coli elt genes
      at a preferred site in Salmonella typhimurium identifies a novel putative
      fimbrial locus.
AB  - An asd-complementing mini-Tn5 transposon was constructed for random insertion of
      the Escherichia coli LT enterotoxin genes (elt) into the genome of Deltaasd
      attenuated strains of Salmonella typhimurium. Transfer of the minitransposon to
      different S. typhimurium strains resulted in random integration only in strain
      chi4072, while in strain chi3987, which harbours the virulence plasmid, over 20%
      of the insertions occurred at the same site. Expression of elt was found to be
      highest in Salmonella isolates carrying the mini-Tn5 integrated at the preferred
      site, which was mapped to an uncharacterised region of the virulence plasmid.
      Sequence analysis of the integration site showed that it lies within an open
      reading frame with sequence similarity to E. coli leuO and contiguous to a novel
      fimbrial locus.

PMID- 9914310
TI  - Expression of bvgAS of Bordetella pertussis represses flagellar biosynthesis of
      Escherichia coli.
AB  - BvgAS is a two-component system of Bordetella pertussis involved in the
      reciprocal regulation of the virulence genes and the flagellar biosynthesis. In
      this study, we found that expression of bvgAS in Escherichia coli also results in
      reduced motility. The repression was relieved by the addition of known chemical
      modulators of BvgAS such as MgSO4 and nicotinic acid, indicating that functional
      BvgAS proteins are required for the negative control of E. coli motility. In
      addition, BvgAS repressed the transcription of the flhDC master operon of E.
      coli, which consequently caused non-flagellation on the cell surface. However,
      expression of BvgAS had no effect on stress-resistant motile mutants of E. coli.
      These data suggest that E. coli may have BvgA-like protein(s) involved in the
      regulatory interactions between the stress response and the flagellar
      biosynthesis.

PMID- 9914311
TI  - Accumulation of ppGpp in symbiotic and free-living nitrogen-fixing bacteria
      following amino acid starvation 
AB  - Following amino acid or ammonium starvation, ppGpp is accumulated by Rhizobium
      meliloti strain 1021 but not by R. meliloti strain 41 or Rhizobium tropici.
      Azorhizobium caulinodans ORS571 produced ppGpp following amino acid deprivation;
      however, the free-living nitrogen-fixing bacteria Azotobacter vinelandii and
      Azomonas agilis did not produce ppGpp. Western blot analysis using anti-RelA
      antibody demonstrated that R. meliloti strain 1021, Azotobacter vinelandii and
      Azorhizobium caulinodans cross-reacted under conditions that detected RelA in
      Escherichia coli CF1648. Cross-reaction was not observed in R. meliloti strain
      41, R. tropici, or Azomonas agilis. All strains that accumulated ppGpp also
      produced high intracellular levels of ATP.

PMID- 9914312
TI  - Cold shock proteins CspB and CspC are major stationary-phase-induced proteins in
      Bacillus subtilis.
AB  - Shortly after the transition from exponential growth to stationary phase, the
      pattern of protein synthesis in Bacillus subtilis changes markedly. Among the
      most profoundly induced proteins are two homologous small acidic proteins, CspB
      and CspC, which are also major cold-shock-induced proteins. The third cold shock
      protein (CSP) in B. subtilis, CspD, is not induced following entry into
      stationary phase. Deletion of both cspB and cspC genes has been previously shown
      to lead to lysis of cells during stationary phase. These findings reveal that
      CSPs in B. subtilis are induced under several stress conditions, and that an
      increase in the synthesis of CspB and CspC is needed for efficient adaptation to
      stationary phase. Enhanced synthesis of CspB occurs through a combination of
      transcriptional and post-transcriptional activation, indicating a mechanism
      similar to that mediating cold shock induction of CSPs. Induction of CSPs in
      bacteria may be triggered by a common signal, the inactivation of ribosomes,
      occurring under both cold shock and stationary-phase conditions.

PMID- 9914313
TI  - Risedronate, a highly effective, short-term oral treatment for Paget's disease: a
      dose-response study.
AB  - Risedronate is a potent pyridinyl bisphosphonate being developed for bone
      diseases such as Paget's disease and osteoporosis. In this study, we compared the
      efficacy, safety, and tolerability of three different doses of oral risedronate
      in 62 patients with severe Paget's disease of bone [serum alkaline phosphatase
      (AP) >3 times the upper limit of normal]. Patients were treated at six study
      centers with either 10, 20, or 30 mg oral risedronate daily for 28 days and
      followed up to day 85. The primary efficacy parameter was percentage change from
      baseline in AP excess. The data show that there is a dose-response with
      risedronate: patients who received 30 mg oral risedronate for 28 days benefited
      most, with a mean percentage decrease in AP excess of 72.2% (20 mg: 57.9%; 10 mg:
      48. 0%). Time to response-the first time point when there was a >/=30% reduction
      from baseline in AP excess and >/=50% reduction from baseline in urinary
      hydroxyproline (HP)/creatinine-was also significantly shorter (median 29 days) in
      the 30 mg group compared with the other two groups (20 mg: 43 days and 10 mg: 71
      days). Long-term follow-up data up to 33 months from the start of the study
      indicated that AP remained below baseline levels for all patients. Histologic
      evaluation of bone formed during risedronate therapy demonstrated that normal
      lamellar bone was formed as opposed to woven pagetic bone, with no evidence of
      osteomalacia. Risedronate was well tolerated. Transient decreases in serum
      calcium and increases in serum intact parathyroid hormone were observed,
      consistent with the pharmacology of risedronate. In conclusion, risedronate
      administered at daily doses of 10, 20, and 30 mg for 28 days was effective in
      reducing the biochemical indices of disease activity in patients with severe
      Paget's disease of bone. A daily dose of 30 mg was most effective without
      compromising safety or tolerability.

PMID- 9914314
TI  - Effects of long-term administration of methotrexate on bone mineral density in
      rheumatoid arthritis.
AB  - Because previous studies of high-dose methotrexate usage have demonstrated an
      effect on bone formation and resorption, this study was done to determine whether
      long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis
      causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was
      measured in 10 Caucasian postmenopausal women who had never received methotrexate
      and 10 Caucasian postmenopausal women who had received the drug for 3 or more
      years. There were no significant differences in BMD at the lumbar spine (L2-L4)
      between patients who had used long-term methotrexate compared with patients never
      treated with methotrexate (1.08 +/- 0.08 g/cm2 versus 0.98 +/- 0.14 g/cm2,
      respectively; P = 0.08). Similarly, there were no significant differences in BMD
      at the femoral neck between methotrexate users and nonusers (0.81 +/- 0.08 g/cm2
      versus 0.76 +/- 0.15 g/cm2, respectively; P = 0.42). These results suggest that
      long-term low-dose methotrexate treatment for rheumatoid arthritis is not
      associated with accelerated bone loss.

PMID- 9914315
TI  - Early and late postmenopausal bone loss is associated with BsmI vitamin D
      receptor gene polymorphism in Japanese women.
AB  - To determine whether vitamin D receptor (VDR) gene polymorphisms are associated
      with bone mineral density (BMD) and bone loss in the Japanese population, VDR
      BsmI RFLPs were analyzed in 191 postmenopausal Japanese women by comparing B
      allele and b allele DNA sequences, and a point mutation was confirmed. We
      examined VDR BsmI restriction fragment length polymorphism (RFLP) with an
      amplification refractory mutation system (ARMS) using this point of mutation. The
      frequency of VDR BsmI alleles in the Japanese population was significantly
      different from that in whites. The bb genotype was identified in 79.6%, of the
      subjects, the Bb genotype in 19.3%, and the BB genotype was in only 1.1%. We find
      no significant differences in lumbar spine baseline BMD between the bb genotype
      and the Bb genotype. In both early and late postmenopausal periods, serial
      measurements of vertebral BMD revealed that subjects with the Bb genotype lost
      BMD faster than those with the bb genotype (P = 0.001). We conclude that there is
      a significant relationship between RFLPs of BsmI VDR and the annual rates of bone
      loss during early and late postmenopausal periods in the Japanese population.

PMID- 9914316
TI  - Factors affecting peak bone density in Japanese women.
AB  - Both genetic and environmental factors have been shown to contribute to the
      determination of bone density. To clarify the interaction between genetic and
      environmental factors affecting peak bone mass, we investigated the correlation
      between bone mineral density (BMD) and physical constitution, vitamin D receptor
      (VDR) genotype, age, age of menarche, history of menstrual dysfunction, and
      exercise in 157 healthy young Japanese women. History of exercise and menstrual
      dysfunction were significant independent predictors of BMD. The VDR genotype also
      affects peak bone density. Exercise has been shown to increase BMD in a similar
      way for each VDR genotype including those women who have the particular genotype
      associated with low bone density. This data indicate that there are complex gene
      environmental interactions particularly in relation to menstrual history,
      exercise, and genetic factors during childhood/adolescence that may have
      implications for the development of adult BMD in women.

PMID- 9914317
TI  - Effect of lifetime occupational physical activity on indices of bone mineral
      status in healthy postmenopausal women.
AB  - The purpose of this study was to examine the effect of lifetime physical activity
      of farmers on skeletal status. Seventy-one healthy, postmenopausal women (mean
      age 52.3 +/- 5.9 years, range 42-61 years) who worked professionally on farms
      were compared with 78 matched controls (mean age 51.8 +/- 5.5 years, range 42-61
      years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the os
      calcis were measured using an ultrasound transmission imaging system. Bone
      mineral density (BMD) of the lumbar spine and femoral neck were measured by dual
      energy X-ray absorptiometry (DXA). Differences in BUA, SOS, and BMD between
      farmers and controls were expressed relative to standard deviation (SD) of the
      farmers. Farmers had significantly higher density values than controls
      (difference = 1.3 SD in the spine and 1.5 SD in the femoral neck, P < 0.0001 for
      both comparisons). Ultrasound values were significantly higher in the farmers
      compared with the controls in calcaneus (difference = 1.1 SD for BUA and 0.7 SD
      for SOS, P < 0.0001 for both comparisons). The difference of spine BMD, femoral
      neck BMD, BUA, and SOS between farmers and controls, as judged by comparison of
      the slopes of the regression lines, was unchanged with age and years since
      menopause. These results suggest that lifetime physical activity has a positive
      effect on bone status of postmenopausal farmers.

PMID- 9914318
TI  - Low bone mass density at multiple skeletal sites, including the appendicular
      skeleton in amenorrheic runners.
AB  - The aim of this study was to investigate any difference in bone mass at different
      sites between female long-distance runners with amenorrhea and those with
      eumenorrhea. We compared 10 amenorrheic and 10 eumenorrheic athletes to determine
      whether athletes with amenorrhea have lower BMD in multiple skeletal regions,
      including weight-bearing lower limbs. The amenorrheic group had experienced
      menstrual dysfunction ranging from 3 to 43 months. As a further control group, 16
      eumenorrheic soccer players were compared with the former two running groups
      regarding their BMD measurements. The two groups were matched for age, height,
      and amount of training. Areal bone mineral density (BMD) was measured and was
      found to be significantly lower in the total body, humerus, spine, lumbar spine,
      pelvis, femoral neck, trochanter, total femur, femur diaphysis, tibia diaphysis
      and in the nonweight-bearing head of the femur in the amenorrheic group. Body
      weight, BMI, fat mass, and body fat percent were significantly lower in the
      amenorrheic group. The differences in the BMD of the head, humerus, femoral neck,
      total femur, femur diaphysis, and tibia diaphysis disappeared when adjusted for
      body weight. Compared with the soccer group, the amenorrheic subjects had
      significantly lower BMD values at all sites except for the head, Ward's triangle,
      and femur diaphysis. Blood samples were obtained in the two running groups for
      analysis of osteocalcin, carboxy terminal telopeptide (ICTP), procollagen I
      (PICP), and estradiol. There were no significant differences between the groups
      but there was a strong tendency towards a lower estradiol level and a higher
      osteocalcin level in the amenorrheic group. A free estradiol index (FE2) was
      derived as the ratio of estradiol to sex hormone binding globulin (SHBG) and was
      significantly lower in the amenorrheic group. No difference in their daily intake
      of total energy, protein, carbohydrates, fiber, calcium, and vitamin D was
      observed. However, both groups showed a surprisingly low energy intake in
      relation to their training regimens. Stepwise regression analyses revealed that
      weight was the best predictor of spine BMD in both groups. Estradiol and FE2 were
      significant predictors of the BMD of the proximal femur in the eumenorrheic
      group, but did not predict any BMD site in the amenorrheic group. In conclusion,
      amenorrhea in athletic women affects trabecular and cortical bone in both axial
      and appendicular skeleton. However, some of the discrepancy can be explained by a
      lower body weight. Physical weight-bearing activity does not seem to completely
      compensate for the side effects of reduced estrogen levels even in weight-bearing
      bones in the lower extremity and spine.

PMID- 9914319
TI  - Radial bone mineral density and estimated rates of change in normal Scottish
      women: assessment by peripheral quantitative computed tomography.
AB  - This study examines normative bone mineral density (BMD) data, as measured by
      peripheral quantitative computed tomography of the ultradistal radius, in 332
      Scottish women aged 18-90 years, comparing it to a recently reported normal
      German population. The normative Scottish data were higher in almost all decades
      compared with German counterpart, percentage differences being +0.002%-+21.6% for
      total (Qtot), and -0.06%-+31.9% for trabecular (Qtrab) BMD. Differences in
      calibration of the Stratec XCT-960 and XCT-900 systems are thought to be largely
      responsible for these differences. Estimated age-related changes were determined
      in the Scottish population. A cubic regression model best fitted age-related
      changes in the whole population, and changes as a function of years postmenopause
      in the postmenopausal subgroup, for Qtot, subcortical (Qscort), and cortical
      (Qcort) BMD, whereas a parabolic regression model best fitted corresponding
      changes in Qtrab BMD. Percentage age-related changes (5 years: 10 years
      postmenopause) in Qtot (-0. 79%-1.12%/year) and Qscort (-0.72%-1.12%/year) were
      greater than Qtrab (-0.53%-0.56%/year) in the early postmenopausal years. Maximum
      age-related changes were found at 20 years postmenopause for Qtot (-1.36%/year),
      Qscort (-1.39%/year), and Qcort (-1.39%/year). This study has highlighted
      variation in normative data derived by different Stratec pQCT systems. The
      estimated age-related changes suggest that early postmenopausal bone loss
      preferentially affects subcortical rather than trabecular bone at the radius.

PMID- 9914320
TI  - Densitometric study of developing femur.
AB  - The purpose of this work was to extend to long bones the study on the
      ossification of human fetal skeleton in relation to conceptual age by a
      quantitative methodological approach. Postero-anterior scans were performed on 29
      dried fetal femora (from 11.5 weeks of conceptual age to term) by a Hologic QDR
      1000 X-ray densitometer with Ultra-Hi-Resolution software. The results were
      expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2).
      BMD was calculated on a rectangular area corresponding to the total length and
      minimum width of the shaft. This area was divided into five equal sections along
      its longitudinal axis in order to estimate the rate of ossification from a spatio
      temporal point of view. Our data show that BMC has a high correlation with
      conceptual age during the whole prenatal life, increasing in the third trimester
      (r >/= 0. 96). During development, BMD is progressively less correlated with
      conceptual age (r = 0.95 in the first half of development, r = 0.68 in the second
      half), particularly according to a bidirectional gradient from the middle to the
      proximal and distal ends of the shaft. Our findings confirm the data obtained in
      our previous studies on the ossification of fetal human spines, and suggest an
      individual variability in bone density at term of development and particularly at
      the level of spongiosa, viz. in the areas mostly involved in architectural
      changes during the morphogenesis of the long bones.

PMID- 9914321
TI  - Temporary brittle bone disease: association with decreased fetal movement and
      osteopenia.
AB  - Infants who present with multiple unexplained fractures pose a difficult
      diagnostic dilemma of child abuse versus intrinsic bone disease. Temporary
      brittle bone disease is a recently described disease characterized by a transient
      bone weakness in the first year of life which presents with multiple, unexplained
      fractures that can be confused with child abuse. The purpose of this study was to
      determine if there are common, historical features in infants with unexplained
      fractures that might suggest a basis for the fractures, and to determine if bone
      density measurements might indicate that such infants have low bone density.
      Medical records were reviewed in 33 infants who were referred for consultation
      for multiple unexplained fractures in which the parents and other caregivers
      denied wrongdoing. In 9 of the infants, radiographic absorptiometry and/or
      computed tomography bone density studies were performed. In 26 of these infants
      the diagnosis of temporary brittle bone disease was made. A normal collagen test
      was found in 17 of the 26 infants studied; 9 infants did not have a collagen test
      because the diagnosis of osteogenesis imperfecta was considered highly unlikely.
      In 25 of them there was a history of decreased fetal movement and/or intrauterine
      confinement. Bone density, as judged by plain X-ray films, was normal in all 26
      cases, but when formally measured by radiographic absorptiometry or computed
      tomography, the bone density measurements were low in 8 of the 9 infants studied.
      These findings implicate decreased fetal movement and intrauterine confinement as
      contributing factors to temporary brittle bone disease and suggest that normal,
      unconstrained fetal movement during pregnancy is important for normal fetal bone
      formation. These findings support the model that bone formation and strength are
      dependent on the mechanical load placed on the bone. The results also demonstrate
      the usefulness of bone density measurements in evaluating the infant with
      multiple unexplained fractures to help distinguish nonaccidental injury from
      intrinsic bone disease.

PMID- 9914322
TI  - Osteoporosis in male and female leprosy patients.
AB  - We measured the bone mineral density (BMD) of 353 leprosy patients (197 males 50
      89 years old, average age 70.2; and 156 females 53-90 years old, average age
      72.9) and serum levels of free testosterone (FT) in 81 males. The BMD of the
      lumbar vertebrae (L2-L4), diaphysis of the radius (1/3 radius), and the neck of
      the femur (neck) was measured using DXA (QDR 4500). The BMD of -2.5 SD YAM (young
      adult mean) in Japanese men and women was used as the cutoff value for
      osteoporosis in the respective genders: BMD of L2-L4, 0.751 g/cm2 (male), 0.747
      g/cm2 (female); 1/3 radius, 0.655 g/cm2 (male), 0.550 g/cm2 (female); neck, 0.581
      g/cm2 (female). The percentages of males with osteoporosis were 31.3% in the
      50th, 32.9% in the 60th, 44.9% in the 70th, and 40.7% in the 80th decade at L2
      L4. Similarly, the percentages were 33.3%, 58.3%, 74.3%, and 75.0%, respectively,
      at 1/3 radius. Among females, the percentages were 22.2%, 41.3%, 44.9%, and
      68.8%, respectively, at L2-L4; 0%, 42.9%, 89.5%, and 78.6%, respectively, at 1/3
      radius; and 11.1%, 38.6%, 67.7%, and 84.6% respectively, at neck. FT in men
      ranged from almost 0 to normal at each decade and BMD levels were significantly
      correlated with FT in all three regions of the skeleton (P < 0.0001). More than
      30% of osteoporosis was found at each decade and FT may be one of the main
      factors affecting BMD in male leprosy patients.

PMID- 9914323
TI  - Influence of antiresorptive agent OST-766 on signal transduction pathways
      involved in parathyroid hormone action.
AB  - The effects of OST-766, an inhibitor of vacuolar H+-ATPase activity, on adenylyl
      cyclase and phospholipase C activity were explored in the osteoblast cell line
      ROS 17/2.8. In fresh homogenates of ROS 17/2.8 cells, OST-766 inhibited adenylyl
      cyclase activity (ACA) in response to guanine nucleotide and forskolin but had no
      effect on basal ACA. OST-766 enhanced the basal generation of IP2, but not that
      formed in response to Ca2+ or guanine nucleotides. In marked contrast, incubation
      of intact ROS 17/2.8 cells with OST-766 for at least 48 hours resulted in an
      increase in basal ACA as well as in response to PTH, guanine nucleotides and
      forskolin. Under similar conditions, the compound also increased IP1, IP2 and IP3
      generation in response to guanine nucleotides and Ca2+. Levels of the guanine
      nucleotide binding proteins Gs and Gi were also increased in OST-766-treated
      cells. The results suggest that the actions of this H+-ATPase inhibitor include
      effects on osteoblasts through PTH-sensitive signal transduction pathways.

PMID- 9914324
TI  - Avian osteoclast cells are stimulated to resorb calcified matrices by and possess
      receptors for leukotriene B4.
AB  - Leukotriene B4 (LTB4) is elevated in inflammatory conditions and appears to be a
      potential mediator of inflammation. We have recently shown that this 5
      lipoxygenase metabolite of arachidonic acid stimulates bone resorption in vitro
      and in vivo. In order to determine the mechanism whereby LTB4 causes bone
      resorption, avian osteoclasts were examined for the effects of LTB4 and for the
      presence of LTB4 receptors. Isolated avian osteoclast mononuclear precursor
      cells, which fuse in culture to form multinucleated cells, were chosen for
      receptor binding studies because this population is a morphologically similar
      source of osteoclasts, and large numbers of these cells can be obtained from egg
      laying hens. Binding of LTB4 and activation would support the hypothesis of a
      direct effect of this compound on osteoclasts. LTB4 stimulated isolated avian
      osteoclasts to form resorption lacunae on calcified matrices and to increase
      their content of tartrate-resistant acid phosphatase (TRAP), a marker of
      activated osteoclasts. Receptor binding studies were performed at day 1, when the
      cells were mononuclear, at day 4, when mononuclear precursors were actively
      fusing, and at day 7, when fusion has slowed. Scatchard analysis of saturation
      binding data showed two classes of binding sites, a high- and low-affinity
      binding site with dissociation constants (KD) of 0.2-0.4 nM and 5. 6-24 nM.
      Association studies showed rapid binding of LTB4 to the cells within 10 minutes.
      These data show that LTB4 accelerates fusion and activates highly enriched
      populations of avian osteoclasts and that LTB4 receptors are present in this cell
      population.

PMID- 9914325
TI  - Expression of mRNA encoding tissue-nonspecific alkaline phosphatase in human
      dental tissues.
AB  - Tissue-nonspecific-type alkaline phosphatase (TNSALP) is found in the bone,
      liver, kidney, and other tissues, and its gene consists of 12 exons with the
      coding sequence beginning in the second exon. Recently, a noncoding first exon
      was identified in the liver message (liver type) which differed from that of the
      previously known osteoblast-derived cDNA sequence (bone type). Although these two
      mRNAs produce an identical protein, they have different promoter regions. It is
      known that ALPs in dental pulp and periodontal ligament are classified into
      TNSALP by their enzymatic and immunological properties, but little is known about
      the expression of ALP mRNAs and the transcriptional mechanisms. In order to
      examine the expression of their mRNA type, specific oligonucleotide primers
      corresponding to two types of mRNAs of human TNSALP were designed and amplified
      by reverse transcription-polymerase chain reaction (RT-PCR). It was found that
      bone-type mRNA was expressed in the human dental tissues such as dental pulp,
      periodontal ligament, and dental sac, whereas liver-type mRNA was not expressed.
      Thus, it was concluded that the human dental tissues express the bone-type
      isozymes and are regulated by the same transcriptional mechanism as in the bone.

PMID- 9914326
TI  - Effects of zinc on human skeletal alkaline phosphatase activity in vitro.
AB  - Inorganic phosphate (Pi) can regulate the level of skeletal alkaline phosphatase
      (ALP) activity in human osteoblast-like cells by stabilizing the enzyme (without
      affecting transcription, ALP release from the cell surface, or the amount of ALP
      protein). These observations suggest that Pi determines the level of ALP activity
      by modulating a process of irreversible inactivation. The current studies were
      intended to examine the hypothesis that this inactivation of ALP activity is
      caused by the dissociation of an active center Zn and that Pi inhibits that
      dissociation. Initial studies showed that Zn, like Pi, could increase ALP
      specific activity in human osteosarcoma SaOS-2 cells in a time- and dose
      dependent manner (e.g., a 50% increase at 0.2 micromol/liter Zn, P < 0.005). This
      effect was specific for Zn (i.e., no similar effect was seen with Ca, Fe, Co, Mg,
      Mn, or Cu), but not for SaOS-2 cells. Zn also increased ALP specific activity in
      (human osteosarcoma) MG-63 cells and in cells derived from normal human vertebrae
      (P < 0.001 for each). The effect of Zn to increase ALP activity was not
      associated with parallel increases in total protein synthesis, collagen
      production, or tartrate-resistant acid phosphatase activity (no change in any of
      these indices), net IGF-2 synthesis (a Zn-dependent decrease, P < 0.005), or PTH
      dependent synthesis of cAMP (a biphasic increase, P < 0.02). Kinetic studies of
      Pi and Zn as co-effectors of ALP activity showed that Zn was a mixed-type
      effector with respect to Pi, whereas Pi was competitive with respect to Zn.
      Mechanistic studies showed that (1) Zn reversed the effect of Pi withdrawal to
      decrease ALP activity, but not by reactivating inactive ALP protein (the process
      required protein synthesis, without increases in ALP mRNA or the level of ALP
      immunoreactive protein); (2) Zn increased the half-life of ALP activity in intact
      cells and after a partial purification; and (3) Pi inhibited the process of ALP
      inactivation by EDTA (which chelates active center Zn). All these findings are
      consistent with the general hypothesis that Pi increases the half-life of
      skeletal ALP by preventing the dissociation of active center Zn and with a
      mechanistic model of skeletal ALP activity in which active center Zn participates
      in Pi-ester binding and/or hydrolysis.

PMID- 9914327
TI  - In vivo treatment with calcitriol (1,25(OH)2D3) reverses age-dependent
      alterations of intestinal calcium uptake in rat enterocytes.
AB  - The vitamin D endocrine system has been involved in the impairment of intestinal
      calcium absorption during aging. Alterations in the nongenomic mechanism of
      calcitriol (1,25-dihydroxy-vitamin D3; [1, 25(OH)2D3] have been recently
      evidenced. In enterocytes isolated from aged rats, 1,25(OH)2D3 stimulation of
      Ca2+ channels through the cAMP/PKA pathway is blunted. We have now investigated
      whether in vivo administration of calcitriol to senescent rats reverses the
      absence of hormonal effects in isolated intestinal cells. In enterocytes from 20
      24-month-old rats given 1,25(OH)2D3 for 3 days (30 ng/100 g bw/day), calcitriol
      (10(-10) M, 3-5 minutes) stimulated Ca2&plus uptake and intracellular cAMP to the
      same degree and protein quinase A (PKA) activity to a lesser degree than in
      enterocytes from young animals. Significantly higher basal levels of cAMP and PKA
      detected in enterocytes from old rats were not affected by prior injection of
      animals with 1,25(OH)2D3. When the aged rats were injected with 25(OH)D3, similar
      Ca2+ influx, cAMP, and PKA responses to in vitro stimulation with calcitriol were
      obtained. 1, 25(OH)2D3-dependent changes in Ca2+ uptake by enterocytes from both
      young and old rats treated with calcitriol were totally suppressed by the cAMP
      antagonist Rp-cAMPS, whereas the response to the agonist Sp-cAMPS was markedly
      depressed in aged animals. These results suggest that intestinal resistance to
      nongenomic 1,25(OH)2D3 stimulation of duodenal cell Ca2+ uptake develops in rats
      upon aging and show that in vivo administration of 1,25(OH)2D3 or its precursor
      to senescent rats restores the ability of the hormone to stimulate duodenal cell
      calcium influx through the cAMP messenger system.

PMID- 9914328
TI  - Cross-sectional study of weight-bearing activity on proximal femur bone mineral
      density.
AB  - In this cross-sectional study we investigated the effect of compressive and
      tensile forces applied on the proximal femur during weight-bearing activities.
      Ninety-seven men (29.9 +/- 1.7 years) were divided into two groups: 69 exercisers
      who had practiced regular high-impact weight-bearing activities for at least 5
      years and 28 controls who had been sedentary for at least 5 years. The maximum
      isometric hip abduction strength was measured. The bone mineral density (BMD) of
      the femoral neck and the greater trochanter was assessed using dual-energy X-ray
      absorptiometry (DXA). Controls were considered as the reference population to
      calculate the Z score. Mean BMD values of the femoral neck were 0.97 g/cm2 on
      both sides in the exercisers and 0.83 g/cm2 on the right side and 0.84 g/cm2 on
      the left side in the controls. Mean BMD values of the greater trochanter were
      0.86 g/cm2 on the right side and 0.87 g/cm2 on the left side in the exercisers,
      0.73 g/cm2 on the right side and 0.72 g/cm2 on the left side in the controls. The
      BMD was significantly higher in exercisers at both trochanteric and cervical
      sites (P = 0. 0001). Both left and right hip abduction strength was significantly
      greater in the exercisers than in the controls (P < 0.05) and was positively
      correlated to cervical and trochanteric BMD (P < 0.01). In the exerciser group,
      the trochanteric Z score was higher than the cervical Z score at both right (P =
      0.06) and left (P = 0.002) sides. Therefore, the proximal femoral BMD was
      significantly greater in exercised subjects as compared with sedentary controls.
      The difference was observed at the level of both the femoral neck (where it is
      known anatomically that only compressive gravitational forces are exerted) and
      the greater trochanter (where it is known that tensile forces are exerted). This
      result suggests the participation of both compressive and tensile forces in the
      mechanisms by which exercise influences bone trophicity.

PMID- 9914329
TI  - Characterization of the mouse proteasome regulator PA28b gene.
AB  - The proteasome regulator PA28, which can be upregulated by IFN, is important in
      the modulation of proteasome activity. Since the proteasome has been implicated
      in the processing of the major histocompatibility complex (MHC) class I antigens,
      it was of interest to determine the regulatory elements of PA28 at the genomic
      level. Although PA28 has been found in different species, the gene layout on the
      chromosome was not determined. In this study, the genetic organization of mouse
      PA28b was characterized. Two copies of the PA28b gene, namely b1 and b2, were
      found by restriction fragment mapping and Southern hybridization. By fluorescence
      in situ hybridization, the location of the two PA28b genes was determined on
      chromosomes 11 and 14. PA28b1 has 11 exons, whereas PA28b2 has no introns and
      appears to be a nonfunctional pseudogene. The 5' promoter region of PA28b1
      contains several transcriptional factor binding sites including two IFN
      responsive elements. The expression levels of PA28 and other gene products
      involved in MHC class I antigen presentation appear to be correlated in various
      tissues. Notably, PA28 is expressed at high levels in immunological tissues such
      as spleen and peripheral blood leukocytes. Taken together, PA28 seems to be co
      regulated with other molecules involved in MHC class I antigen presentation.

PMID- 9914330
TI  - Polymorphism and transcription of Mhc class I genes in a passerine bird, the
      great reed warbler.
AB  - The class I genes of the major histocompatibility complex (Mhc) are here
      investigated for the first time in a passerine bird. The great reed warbler is a
      rare species in Sweden with a few semi-isolated populations. Yet, we found
      extensive Mhc class I variation in the study population. The variable exon 3,
      corresponding to the alpha2 domain, was amplified from genomic DNA with
      degenerated primers. Seven different genomic class I sequences were detected in a
      single individual. One of the sequences had a deletion leading to a shift in the
      reading frame, indicating that it was not a functional gene. A randomly selected
      clone was used as a probe for restriction fragment length polymorphism (RFLP)
      studies in combination with the restriction enzyme Pvu II. The RFLP pattern was
      complex with 21-25 RFLP fragments per individual and extensive variation. Forty
      nine RFLP genotypes were detected in 55 tested individuals. To study the number
      of transcribed genes, we isolated 14 Mhc class I clones from a cDNA library from
      a single individual. We found eight different sequences of four different lengths
      (1.3-2.2 kilobases), suggesting there are at least four transcribed loci. The
      number of nonsynonymous substitutions (dN) in the peptide binding region of exon
      3 were higher than the number of synonymous substitutions (dS), indicating
      balancing selection in this region. The number of transcribed genes and the
      numerous RFLP fragments found so far suggest that the great reed warbler does not
      have a "minimal essential Mhc" as has been suggested for the chicken.

PMID- 9914332
TI  - Mhc class I and non-class I gene organization in the proximal H2-M region of the
      mouse.
AB  - A bacterial artificial chromosome (BAC) contig was constructed across the
      proximal part of the H2-M region from the major histocompatibility complex (Mhc)
      of mouse strain 129 (H2bc). The contig is composed of 28 clones that span
      approximately 1 megabasepair (Mb), from H2-T1 to Mog, and contains three H2-T
      genes and 18 H2-M genes. We report the fine mapping of the H2-M class I gene
      cluster, which includes the previously reported M4-M6, the M1 family, the M10
      family, and four additional class I genes. All but two of the H2-M class I genes
      are conserved among haplotypes H2k, H2b, and H2bc, and only two genes are found
      in polymorphic HindIII fragments. Six evolutionarily conserved non-class I genes
      were mapped to a 180 kilobase interval in the distal part of the class I region
      in mouse, and their order Znf173-Rfb30-Tctex5-Tctex6- Tctex4-Mog was found
      conserved between human and mouse. In this Znf173-Mog interval, three mouse class
      I genes, M6, M4, and M5, which are conserved among haplotypes, occupy the same
      map position as the human HLA-A class I cluster, which varies among haplotypes
      and is diverged in sequence from the mouse genes. These results further support
      the view that class I gene diverge and evolve independently between species.

PMID- 9914331
TI  - Identification and genetic mapping of Xenopus TAP2 genes.
AB  - The amphibian Xenopus laevis is one non-mammalian vertebrate in which the major
      histocompatibility complex (MHC) has been analyzed extensively. Class IIbeta,
      class Ia, LMP2, LMP7, HSP70, C4, Factor B, and Ring3 genes have been identified
      and mapped to the MHC. Here, we report the isolation of a transporter associated
      with antigen processing (TAP) gene, TAP2, and demonstrate its linkage to the MHC.
      While the ATP-binding region of Xenopus TAP2 is highly conserved in evolution,
      amino acid identity to other vertebrate TAP proteins was not detected in the N
      terminal region. Segregation analysis of 34 individuals from two families showed
      exact restriction fragment length polymorphism matching between the MHC class Ia
      gene and the one TAP2 gene demonstrating linkage conservation since the
      mammalian/amphibian divergence approximately 350 million years ago. In addition,
      one non-MHC-linked TAP2-hybridizing fragment was detected in approximately half
      of the individuals tested. Interestingly, TAP2 allelic lineages appear to match
      those of LMP7 and classical class I, which previously were categorized into two
      highly divergent groups that emerged at least 60 million years ago. Similar to
      LMP7 and class Ia,TAP2 is expressed ubiquitously with highest levels in intestine
      and spleen.

PMID- 9914333
TI  - MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus
      oedipus), have evolved by an active process of loci turnover.
AB  - Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus),
      express classical G-related major histocompatibility complex (MHC) class I
      molecules with unusually limited polymorphism and variability. Three G-related
      loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been
      identified by cDNA library screening and extensive PCR analysis of both cDNA and
      genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily
      Callitrichinae (tamarins and marmosets) appears to express its own unique set of
      MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of
      unique MHC class I genes in the Callitrichinae genera, resulting from an active
      process of duplication and inactivation of loci, may account for the limited
      diversity of the MHC class I genes in the cotton-top tamarin. To determine the
      nature of the entire complement of MHC class I genes in the cotton-top tamarin,
      we synthesized a genomic DNA library and screened it with MHC class I-specific
      probes. We isolated nine new MHC class I pseudogenes from this library. These
      newly isolated tamarin G-related MHC class I pseudogenes are not closely related
      to any of their functional counterparts in the tamarin, suggesting that they do
      not share a recent common ancestral gene with the tamarin's currently expressed
      MHC class I loci. In addition, these tamarin sequences display a high rate of
      nonsynonymous substitutions in their putative peptide binding region. This
      indicates that the genes from which they have derived were likely subject to
      positive selection and, therefore, were once functional. Our data support the
      notion that an extremely high rate of loci turnover is largely responsible for
      the limited diversity of the MHC class I genes in the cotton-top tamarin.

PMID- 9914334
TI  - Analysis of sheep T-cell receptor beta-chain heterogeneity.
AB  - We analyzed nucleotide and deduced amino acid sequence heterogeneity of sheep T
      cell receptor beta-chain cDNAs isolated from an anchored-polymerase chain
      reaction library. Evaluation of 34 individual rearrangements has defined 18 new
      beta-chain variable region sequences which have been clustered into 13 families.
      Presumptive allelic polymorphisms of four of these variable regions have been
      defined, as well as ten distinct beta-chain joining region sequences. The present
      analysis indicates that sheep T-cell receptor beta-chains are composed of
      characteristic leader, variable, joining, and constant region sequences, and that
      imprecise joining and N-region addition contribute significantly to diversity in
      the third hypervariable region. Thus, it appears that sheep, like all other
      mammals studied to date, employ somatic rearrangement of multiple germline genes
      to create beta-chain heterogeneity. These findings have allowed us to estimate
      the diversity of the sheep T-cell receptor beta-chain variable region repertoire,
      and they provide information that will permit the evaluation of the role that
      specific T-cell populations play in naturally occurring and experimental diseases
      of sheep.

PMID- 9914335
TI  - The MHC of a broiler chicken line: serology, B-G genotypes, and B-F/B-LB
      sequences.
AB  - Although the major histocompatibility complex of chickens (encoded in the B
      complex) has been studied for a number of years, almost all work has focused on
      the White Leghorn breed. Broiler (meat-type) chickens were derived from other
      breeds, including Cornish and Plymouth Rock. It was our hypothesis that new B
      haplotypes, not previously identified in White Leghorns, might be present in
      lines of broiler chickens. Furthermore, alloantisera used to identify B serotypes
      in Leghorn lines reportedly do not work well outside the line in which they were
      raised, with the result that broiler B haplotypes have not been incorporated into
      the universal nomenclature system. Our approach was to use a panel of B
      alloantisera produced to identify B serotypes within a commercial broiler breeder
      line (designated line A). B homozygotes identified serologically were compared by
      B-G genotyping using restriction fragment length polymorphism analysis.
      Furthermore, reverse transcription-polymerase chain reaction was used to amplify
      variable domains of expressed B-LB and B-F genes of homozygotes of most of the B
      serotypes in Line A, followed by cloning and nucleotide sequence determination.
      Comparison of B-LB and B-F sequences with standard Leghorn haplotypes
      demonstrated the existence of new alleles of B-L and B-F in a broiler breeder
      line, as well as the presence of alleles previously identified in Leghorns. In
      some cases, Leghorn-type alleles were in linkage with different B-G alleles in
      the broiler line than the common haplotypic associations found in Leghorn lines.

PMID- 9914337
TI  - Cloning of cattle CD80.

PMID- 9914336
TI  - Amino-terminal sequencing of sheep CD1 antigens and identification of a sheep
      CD1D gene.
AB  - The anti-CD1 monoclonal antibodies IAH-CC14 and SBU-T6 were used to immunopurify
      CD1 antigens from sheep thymocytes. The amino-terminal sequence of IAH-CC14
      yielded 13 amino acids, and 29 amino acids were obtained from the SBU-T6 antigen.
      The sequence of the IAH-CC14 antigen was 100% identical to the predicted sequence
      of the sheep CD1B clone, SCD1B-42. The 29 amino acid sequence of the SBU-T6
      antigen did not match identically with the derived amino acid sequence of any of
      the previously reported sheep CD1 genes but had closest similarity to the derived
      sequence of human CD1E. Degenerate polymerase chain reaction primers based on
      this sequence identified a group 2 sheep CD1 gene. The predicted amino acid
      sequence of this gene shows that it is not identical to the SBU-T6 peptide,
      indicating that a different, CD1D-like gene was cloned.

PMID- 9914338
TI  - T-cell proliferative response is controlled by locus Tria3 on mouse chromosome
      17.

PMID- 9914339
TI  - Development of intra-natural killer complex (NKC) recombinant and congenic mouse
      strains for mapping and functional analysis of NK cell regulatory loci.

PMID- 9914340
TI  - Polymorphisms in the Tnfa gene of different inbred mouse strains.

PMID- 9914343
TI  - Oesophageal atresia in theory and in practice.

PMID- 9914344
TI  - Intrinsic innervation of the oesophagus in fetal rats with oesophageal atresia.
AB  - Although the aetiology of oesophageal dysmotility after repair of oesophageal
      atresia and tracheo-oesophageal fistula (OA-TOF) remains controversial,
      oesophageal dysmotility also is present in isolated TOF or OA before surgery,
      suggesting a congenital cause. Our previous work with a model of OA-TOF in fetal
      rats demonstrated an abnormality in the course and branching pattern of the vagus
      nerve. However, little is known about the intramural nervous components of the
      atretic oesophagus. The intrinsic innervation of the atretic oesophagus was
      examined by immunohistological staining to see if there is an abnormality that
      might account for dysmotility. OA-TOF was induced in fetal rats by injecting
      adriamycin intraperitoneally into pregnant rats. Forty-eight controls, 40 OA-TOF,
      and 6 treated fetuses without OA-TOF were recovered. Whole-mount preparations of
      each oesophagus were stained with fluorescent antibodies against neuron-specific
      enolase (NSE), vasoactive intestinal peptide (VIP), substance P (SP), and
      calcitonin gene-related peptide (CGRP). Compared with control fetuses, the
      density of the nerve plexus, ganglia, and number of cell bodies per ganglion
      immunostained by NSE, VIP, or SP was significantly reduced in OA-TOF fetuses.
      CGRP-immunoreactive nerve fibres in the oesophageal wall of both control and OA
      TOF animals were found to be connected with extrinsic nerve bundles. No plexus
      like nerve fibre network was observed. The results of the present study
      demonstrated significant abnormalities of the intramural nervous components of
      the oesophagus in OA-TOF fetal rats, involving both the excitatory (SP-labelled)
      and inhibitory (VIP-labelled) intramural nerves. These abnormalities may underlie
      the oesophageal dysmotility seen in OA-TOF patients.

PMID- 9914345
TI  - Abnormal enteric nerve morphology in atretic esophagus of fetal rats with
      adriamycin-induced esophageal atresia.
AB  - Gastroesophageal reflux is common in children after successful repair of
      esophageal atresia (EA), and may be related to a congenital neuronal abnormality
      of the esophagus. This study employed a fetal rat model of adriamycin-induced EA
      to investigate whether the innervation of the esophagus is abnormal in EA. The
      fetal rats were divided into four groups: (1) normal controls; (2) a saline
      injected controls; (3) adriamycin administered but without the development of EA;
      and (4) adriamycin-induced EA. The distal esophageal segments were immunostained
      with a general neural marker, protein gene product 9.5 (PGP). Immunoreactivity
      per cross-sectional area (/xsa) was measured with an image analyzer. The extent
      of the esophageal circumference encircled by PGP-stained nerve tissue was
      assessed. While there was no significant difference in PGP immunoreactivity/xsa
      between the groups, the near-complete ring of nerve tissue along the plane of the
      myenteric plexus was replaced by clusters of nerve tissue in the atretic group
      (normal vs EA, P = 0. 001, Mann-Whitney U test). The abnormal distribution of
      nerve tissue in the atretic esophagus may be contributing factor in the
      esophageal dysmotility seen in EA.

PMID- 9914346
TI  - Visceral anomalies in prenatally adriamycin-exposed rat fetuses: a model for the
      VATER association.
AB  - Adriamycin is teratogenic if given to pregnant rats. A wide range of anomalies
      involving the gastrointestinal, renal, and cardiovascular systems has been
      described, similar to the VATER association, yet it is not known if they are
      identical to the human pattern. The aim of this study was to document the
      visceral anomalies in rat fetuses exposed to adriamycin and to determine their
      similarities with the congenital defects in humans with the VATER association.
      The results revealed a spectrum of very similar anomalies. Furthermore, the
      characteristics of the tracheo-oesophageal anomalies had a lot of features in
      common with the human pattern. We conclude that the adriamycin-treated fetal rat
      is an excellent model for studying the VATER association.

PMID- 9914347
TI  - Pathohistological study of adriamycin-induced tracheal agenesis in the fetal rat.
AB  - There have been few studies of tracheal agenesis (TA) because it is an extremely
      rare condition and is invariably fatal. However, it is recognised to be
      associated with a variety of oesophageal abnormalities, including oesophageal
      atresia (OA) and communicating bronchopulmonary foregut malformations (CBPFM).
      Except for some gross pathological reports, there has been no detailed
      histological investigation of this congenital abnormality. Adriamycin-induced TA
      in fetal rats provides a means of studying this uncommon condition, including its
      relationship to oesophageal abnormalities. TA was induced in rat features by
      intra-peritoneal injection of adriamycin (2 mg/kg) into timed-pregnant rats on
      days 6-9. Their 33 fetuses were removed by caesarean section, cut transversely,
      and stained after which the slides were examined. OA developed in 27/33
      adriamycin-treated fetuses, TA occurred in 5. Four had type III while the 5th had
      type II TA. The oesophagus of fetuses with TA acquired tracheal features in the
      region where both ectopic bronchi originated. Two fetuses with TA also had OA,
      and 4 had a CBPFM. Other abnormalities detected involved the gastrointestinal,
      urinary and cardiovascular systems. The association of TA and oesophageal
      abnormalities suggests that there may be a spectrum of abnormalities comprising a
      number of variants, which may have a common aetiology. The other abnormalities co
      existing in this animal model mirror those found in reported cases of human TA.
      Ultimately, the rat model of OA and TA may give insight into the embryogenesis of
      these malformations.

PMID- 9914348
TI  - Association of oesophageal atresia and cholecystohepatic duct.
AB  - A rare hepatobiliary malformation in which the common hepatic duct drains
      directly into the gallbladder or the cystic duct (cholecystohepatic duct) is
      described in two children born with oesophageal atresia. Attention is drawn to
      the rarity of this combination. A brief review of the literature of
      cholecystohepatic and accessory hepatic ducts is also presented.

PMID- 9914350
TI  - The frequency, significance, and management of a right aortic arch in association
      with esophageal atresia.
AB  - An unrecognised right aortic arch (RAA) found at thoracotomy may complicate the
      repair of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF). This
      paper analyses the patient characteristics, peri-operative management, and
      outcome of 16 infants with a RAA, and proposes management guidelines. Between
      1948 and 1996, 709 patients with OA/TOF were admitted to the Royal Children's
      Hospital, of whom 13 had a RAA. Three additional cases from two other paediatric
      surgical units were included. All 16 case records were reviewed retrospectively.
      The overall incidence of RAA in OA was 1.8%. Neither a chest radiograph in 16,
      nor antenatal ultrasonography in 7 detected a RAA. Post-natal echocardiography
      (ECHG) detected a RAA in only 1 of 7 infants examined; that patient underwent
      repair of the OA through a left (L) thoracotomy. The other 15 infants underwent
      initial right (R) thoracotomy. Six of these had a complete repair from the R side
      and 5 had division of the fistula only; 2 of these 5 had initial division of the
      fistula, and the OA was repaired through a repeat R thoracotomy 4 and 7 weeks
      later. In the remaining 4 infants where the fistula could not be located at the
      initial R thoracotomy, complete repair proved possible through the L chest. Three
      of these infants underwent an immediate L thoracotomy; the 4th had a delayed L
      thoracotomy 1 week later. There were 6 deaths: these occurred early in the study
      and were related to severe prematurity, congenital heart disease (CHD), and post
      operative respiratory complications. CHD was identified in 11 of 16 infants
      (71%). Routine pre-operative ECHG is unreliable in determining the laterality of
      the aortic arch. Should a RAA be encountered during a R thoracotomy for OA, it is
      often possible to divide the fistula and repair the OA from that side, but where
      repair looks potentially difficult it is wise to proceed to an immediate L
      thoracotomy.

PMID- 9914349
TI  - Gastric perforation in infants with oesophageal atresia and distal tracheo
      oesophageal fistula.
AB  - Gastric perforation (GP) is a well-recognised complication of oesophageal atresia
      (OA) with distal tracheo-oesophageal fistula (TOF), and is usually associated
      with extreme prematurity, hyaline membrane disease, and the requirement for
      assisted ventilation. The presentation is sudden, and leads to further
      deterioration in respiratory function because of increasing abdominal distension
      from pneumoperitoneum and splinting of the diaphragm. Unrelieved, the infant
      becomes increasingly hypoxic and may die. A review of six infants with OA and
      distal TOF in whom GP occurred has enabled us to develop the following guidelines
      for the appropriate initial surgical management of this complication: (1) Needle
      paracentesis of the abdomen en route to surgery if the infant continues to
      deteriorate; (2) Urgent laparotomy to decompress the abdomen and to occlude the
      lower oesophagus with a catheter introduced through the GP; (3) Thoracotomy and
      division of the fistula; (4) Oesophageal anastomosis if the infant's condition
      improves sufficiently and the anatomy is favourable; and (5) Repair of the GP and
      formation of a gastrostomy.

PMID- 9914351
TI  - Graded compression ultrasonography in the assessment of the "tough decision"
      acute abdomen in childhood.
AB  - The diagnosis of acute appendicitis in childhood is frequently difficult. In some
      situations the need to operate is clear, but in others the decisions may be much
      "tougher" because the clinical findings are equivocal. This is a retrospective
      study of a consecutive series of 253 children presenting with "acute abdominal
      pain? appendicitis" who had graded compression ultrasonography (GCUS) because the
      clinical scenario did not warrant immediate laparotomy. This represents 30% of
      all cases seen in the study period. The aim of the study was to examine the role
      of GCUS and a clinical scoring system (the Alvarado score) in patients in whom
      the diagnosis is uncertain.

PMID- 9914352
TI  - Early repair of inguinal hernia in premature babies.
AB  - Inguinal hernia (IH) is relatively common in premature newborn infants, and the
      timing of surgical correction is controversial. We studied 40 premature infants
      who developed an IH and who were initially treated in a neonatal intensive care
      unit. Birth weight (BW) ranged from 492 to 2,401 g; 21 infants had a BW less than
      1,000 g. The weight of the infants at operation ranged from 1,000 to 4,400 g.
      Twenty-one patients underwent herniotomy within 2 weeks after the diagnosis
      (short waiting group), in which 1 case of incarceration occurred; 19 waited
      longer than 2 weeks between diagnosis and surgery (long waiting group). Two cases
      of strangulation occurred in this latter group, and in 1 of those testicular
      necrosis occurred. Operation time was analysed in boys with bilateral herniotomy
      (n = 25): the short waiting group (n = 12) showed a significantly reduced
      operation time compared to the long waiting group (n = 13). Patients weighing
      less than 1,000 g at birth (n = 21) had a longer average waiting period for
      surgery. In the group of male patients with bilateral herniotomy, average
      operation time was longer in the group weighing less than 1,000 g at birth (n =
      13) than in the group over 1,000 g (n = 12). Body weight at surgery did not
      affect operation time. It is concluded that early hernia repair should be
      considered in premature infants to avoid operative difficulties and gonadal
      ischaemia caused by incarceration.

PMID- 9914353
TI  - Testicular volume of boys after inguinal herniotomy: combined clinical and
      radiological follow-up.
AB  - A total of 173 boys aged 10 to 179 months with previous unilateral inguinal
      herniotomy were called back for follow-up. Clinical and ultrasound examinations
      of the scrotum were performed. The interval between operation and follow-up was 6
      to 123 months (mean 31.68 months). One boy (0.58%) had a more than 50% and 10
      (5.8%) had a more than 25% decrease in testicular volume on the operated side
      when compared with the non-operated side.

PMID- 9914354
TI  - Synchronous bilateral Wilms' tumor.
AB  - Synchronous bilateral Wilms' tumor (WT) accounts for 5% of all WTs. Of 34 cases
      of WT we treated, 7 (20.6%) were bilateral, 5 of them males. This high frequency
      of bilaterality as well as the male preponderance in our series is different from
      that reported in other parts of the world; this may reflect regional variations
      of WT. The details of diagnosis, therapy, including the role of preoperative
      chemotherapy, and outcome are presented.

PMID- 9914355
TI  - Bilateral Wilms' tumor.
AB  - During a 16-year period, 49 children were treated for Wilms' tumor (WT); 7 were
      bilateral, 5 synchronous and 2 metachronous. The age at primary diagnosis was 6
      months to 5 years (mean 2.4 years). All but 1 child received preoperative
      chemotherapy with tumor reduction. Unilateral nephrectomy was performed in 2
      metachronous cases. In 3 synchronous WTs, the tumor was enucleated in 5 kidneys
      and a heminephrectomy was performed in 1 kidney with a double pelvis. Two
      children were not operated upon. At relapse in the contralateral kidney the tumor
      was enucleated. Three patients died of WT, 1 is alive with disease, and 3 are
      without evidence of disease. Renal salvage procedures were technically feasible
      without complications and are advocated to preserve renal function.

PMID- 9914356
TI  - Inhalation burns in children.
AB  - Survival from serious burns in children has improved substantially in recent
      years. Mortality is predominantly determined by the total body surface area
      burned and the often unrecognised inhalation injury. A retrospective review of
      4,451 consecutive children with thermal injuries over a 10-year period was
      undertaken to determine the incidence, clinical presentation, and pathology of
      inhalation injury and its contribution to morbidity and mortality. Inhalation
      burns were diagnosed clinically and confirmed endoscopically and post-mortem in
      97 (2.2%) children; 77 sustained fire burns (mean age 4 years) and 20 hot-water
      burns (mean age 18 months). The Moylan classification stratified them into upper
      airway burns in 59 children, major-airway burns in 29, and parenchymal burns in
      44. Major-airway burns were always seen in conjunction with either upper-airway
      or parenchymal injury. Stridor and acute progressive respiratory distress were
      the two main symptoms, the onset of which was occasionally delayed for up to 72
      h. Endoscopy was most helpful in confirming the diagnosis and determining airway
      management. Endotracheal intubation was needed in more than 50% of children,
      usually for less than 5 days, and was converted to tracheostomy in only 6.
      Persistent laryngeal and tracheal damage was identified in 4. Secondary pneumonia
      occurred in 41.5% of children with fire burns and 55% with hot-water burns.
      Extensive surface burns, parenchymal injury, and secondary pneumonia all
      contributed to the significant mortality. Post-mortem findings corroborated
      clinical and endoscopic evidence. This study suggests that inhalation burns were
      often not recognised, could present late, and usually had significant
      consequences. Early clinical diagnosis, supported by endoscopic findings and
      appropriate management, is essential if the high morbidity and mortality amongst
      these children is to be improved.

PMID- 9914357
TI  - An unusual congenital nasopharyngeal teratoma.
AB  - A case of congenital nasopharyngeal teratoma with invasion of the skull base and
      right temporal region is reported.

PMID- 9914358
TI  - Familial bilateral congenital diaphragmatic hernia.
AB  - Familial inheritance of congenital diaphragmatic hernia is uncommon. We report
      two siblings with identical bilateral diaphragmatic defects.

PMID- 9914359
TI  - Multiple organ malrotation syndrome with duodenal atresia: a case report.
AB  - Duodenal atresia (DA) can be associated with multiple anomalies. Multiple organ
      malrotation syndrome (MOMS) involves laevoversion of the liver and gall bladder
      and dextroversion of the stomach and spleen. We report a case of MOMS with DA.
      Embryologic aspects, investigation, and treatment are discussed.

PMID- 9914360
TI  - Actinomycosis of the appendix in childhood.
AB  - Abdominal actinomycosis (AMC) is a rare infection in children. The appendix is
      the most common intra-abdominal organ involved. It presents as an
      undifferentiated mass, forming abscesses and fistulas in the right lower
      quadrant. The case of a 15-year-old girl with a AMC of the appendix detected by
      the pathologist after routine appendectomy is discussed. Long-term antibiotic
      treatment and follow-up by ultrasound and laboratory controls are necessary.

PMID- 9914361
TI  - Sewing-pin perforation of the appendix into the bladder.
AB  - We report a 2.5-year-old child who presented with an acute abdomen caused by the
      perforation of a sewing pin through her appendix that had started to penetrate
      the wall of the bladder.

PMID- 9914362
TI  - Ectomesenchymoma of the prostate: histological diagnostic criteria.
AB  - A 5-month-old infant with an ectomesenchymoma (EMCH) of the prostate is
      described. The tumour was composed of embryonal rhabdomyosarcoma (RMS) and
      ganglioneuroma. Eight months after presentation the patient died of recurrent
      tumour, which caused intestinal obstruction. The tumour was initially diagnosed
      as an embryonal RMS on trans-rectal needle biopsies. The diagnosis of an EMCH is
      difficult if not impossible to make on needle-biopsy specimens. We suggest that
      pathologists should always consider an EMCH when confronted with a RMS or
      neuroectodermal tumour, and the use of immunohistochemical stains is recommended
      in this situation.

PMID- 9914363
TI  - Prenatally diagnosed cystic neuroblastoma.
AB  - An exceedingly rare case of prenatally diagnosed cystic neuroblastoma (NB) is
      described. Prenatal ultrasonography at 28 weeks' gestation revealed a cystic
      right suprarenal mass that measured 15 x 17 mm in diameter. The mass increased
      parallel to fetal size until it was 41 x 44 mm in diameter at 39 weeks'
      gestation. Magnetic resonance imaging performed prenatally and after delivery
      showed two different intracystic intensities with fluid levels, suggesting
      intracystic hemorrhage. The patient underwent a right adrenalectomy at 20 days of
      age, and the resected tumor was diagnosed as a poorly-differentiated
      ganglioneuroblastoma. Eight months after surgery, the patient is generally
      healthy with no evidence of recurrence. We reviewed 25 additional cases of
      prenatally diagnosed adrenal cystic NB and examined the clinical features of this
      rare entity.

PMID- 9914365
TI  - Papers from the 4th international workshop on chromosome segregation and
      aneuploidy, porto 1998 

PMID- 9914364
TI  - Thermography of Clostridium perfringens infection in childhood.
AB  - Gas gangrene is not a frequently encountered toxic wound infection in childhood.
      We present a case of postoperative Clostridium perfringens infection with
      proximal forearm myonecrosis. In order to reveal the full extent of tissue
      viability in the right upper extremity, infrared thermography was performed.
      Although dyschromia was evident in the proximal forearm, thermographs revealed
      viable tissue only up to the supracondylar region. Angiography, which provided
      valuable clues to the patency of the vascular supply, and subsequent
      intraoperative findings confirmed the extent of tissue perfusion as revealed by
      infrared thermography.

PMID- 9914366
TI  - Telomerase, Ku, and telomeric silencing in Saccharomyces cerevisiae.
AB  - Telomeres comprise a specialized chromosome end structure distinct from the
      standard nucleosomal architecture of the remainder of the genome. Telomere
      maintenance and chromosome stability require both replication of telomeric
      sequences by telomerase and telomeric end protection through binding of proteins.
      We have shown that Cdc13p and the heterodimer Ku are required, along with
      telomerase, for full telomere function, and we have proposed that Ku and Cdc13p
      contribute distinct roles in end protection. Ku has recently been shown to
      exhibit defects in transcriptional repression of telomere-proximal genes, known
      as telomere position effect (TPE), or telomeric silencing. We investigate here
      whether alterations in genes involved in the telomerase pathway also exhibit TPE
      defects and find that deletion or overexpression of EST1 or EST2 does not
      significantly affect telomeric silencing. However, telomeric silencing is
      derepressed upon overexpression of certain nonfunctional alleles of each. In
      addition, we determined that overproduction of telomerase pathway components
      partially alleviates the TPE defect in hdf1Delta cells. This indicates that there
      is genetic crosstalk between these two telomere maintenance pathways, and
      suggests that overproduction of telomerase pathway components may at least
      partially compensate for the loss of Ku in maintaining telomeric silencing.

PMID- 9914367
TI  - A neocentromere on human chromosome 3 without detectable alpha-satellite DNA
      forms morphologically normal kinetochores.
AB  - A neocentromere at 3q26 was observed in a father and his daughter on a chromosome
      3 with deleted centromeric region. No alpha-satellite DNA was detectable at the
      3q26 neocentromere, but it was weakly positive with anticentromere (CREST)
      antibodies. Electron microscopy showed that the neocentromere formed microtubule
      associated kinetochores with normal morphology and of the same size as the
      kinetochores of other large chromosomes. The deleted centromere formed a small
      linear marker chromosome that reacted strongly with anticentromere antibodies,
      but showed reduced kinetochore size. The 3q26 neokinetochore was stable under
      adverse growth conditions, which often caused kinetochore loss in the original 3
      centromere on the small marker.

PMID- 9914368
TI  - A new look at kinetochore structure in vertebrate somatic cells using high
      pressure freezing and freeze substitution.
AB  - Three decades of structural analysis have produced the view that the kinetochore
      in vertebrate cells is a disk-shaped structure composed of three distinct
      structural domains. The most prominent of these consists of a conspicuous
      electron opaque outer plate that is separated by a light-staining electron
      translucent middle plate from an inner plate associated with the surface of the
      pericentric heterochromatin. Spindle microtubules terminate in the outer plate
      and, in their absence, a conspicuous corona of fine filaments radiates from the
      cytoplasmic surface of this plate. Here we report for the first time the
      ultrastructure of kinetochores in untreated and Colcemid-treated vertebrate
      somatic (PtK1) cells prepared for optimal structural preservation using high
      pressure freezing and freeze substitution. In serial thin sections, and electron
      tomographic reconstructions, the kinetochore appears as a 50-75 nm thick mat of
      light-staining fibrous material that is directly connected with the more electron
      opaque surface of the centromeric heterochromatin. This mat corresponds to the
      outer plate in conventional preparations, and is surrounded on its cytoplasmic
      surface by a conspicuous 100-150 nm wide zone that excludes ribosomes and other
      cytoplasmic components. High magnification views of this zone reveal that it
      contains a loose network of light-staining, thin (<9 nm diameter) fibers that are
      analogous to the corona fibers in conventional preparations. Unlike the
      chromosome arms, which appear uniformly electron opaque, the chromatin in the
      primary constriction appears mottled. Since the middle plate is not visible in
      these kinetochore preparations this feature is likely an artifact produced by
      extraction and coagulation during conventional fixation and/or dehydration
      procedures.

PMID- 9914369
TI  - Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore
      requires Bub1 but not Zw10 or Rod.
AB  - We report here the isolation and molecular characterization of the Drosophila
      homolog of the mitotic checkpoint control protein Bub3. The Drosophila Bub3
      protein is associated with the centromere/kinetochore of chromosomes in larval
      neuroblasts whose spindle assembly checkpoints have been activated by incubation
      with the microtubule-depolymerizing agent colchicine. Drosophila Bub3 is also
      found at the kinetochore regions in mitotic larval neuroblasts and in meiotic
      primary and secondary spermatocytes, with the strong signal seen during prophase
      and prometaphase becoming increasingly weaker after the chromosomes have aligned
      at the metaphase plate. We further show that the localization of Bub3 to the
      kinetochore is disrupted by mutations in the gene encoding the Drosophila homolog
      of the spindle assembly checkpoint protein Bub1. Combined with recent findings
      showing that the kinetochore localization of Bub1 conversely depends upon Bub3,
      these results support the hypothesis that the spindle assembly checkpoint
      proteins exist as a multiprotein complex recruited as a unit to the kinetochore.
      In contrast, we demonstrate that the kinetochore constituents Zw10 and Rod are
      not needed for the binding of Bub3 to the kinetochore. This suggests that the
      kinetochore is assembled in at least two relatively independent pathways.

PMID- 9914370
TI  - The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during
      prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.
AB  - The kinetochore binds an evolutionarily conserved set of checkpoint proteins that
      function to monitor whether chromosomes have aligned properly at the spindle
      equator. Human cells contain two related protein kinases, hBUB1 and hBUBR1, that
      appear to have evolved from a single ancestral BUB1 gene. We generated hBUB1- and
      hBUBR1-specific antibodies so that the localization patterns of these kinases
      could be directly compared. In the human U2OS osteosarcoma cell line, hBUB1 first
      appeared at kinetochores during early prophase before all kinetochores were
      occupied by hBUBR1 or CENP-F. Both proteins remained at kinetochores throughout
      mitosis but their staining intensity was reduced from anaphase onward.
      Kinetochores of unaligned chromosomes exhibited stronger hBUB1 and hBUBR1
      staining. Immunoelectron microscopy showed that hBUBR1 appeared to be
      concentrated in the outer kinetochore plate and in some instances the inner plate
      as well. When chromosome spreads were examined by light microscopy, hBUB1 and
      hBUBR1 were coincident with CENP-E. This suggests that both kinases are
      concentrated near the surface of the kinetochore where they can monitor
      kinetochore-microtubule interactions.

PMID- 9914371
TI  - Microinjection of antibodies to centromere protein CENP-A arrests cells in
      interphase but does not prevent mitosis.
AB  - Centromere protein CENP-A is a histone H3-like protein associated specifically
      with the centromere and represents one of the human autoantigens identified by
      sera taken from patients with the CREST variant of progressive systemic
      sclerosis. Injection of whole human autoimmune serum to the centromere into
      interphase cells disrupts some mitotic events. It has been assumed that this
      effect is due to CENP-E and CENP-C autoantigens, because of the effects of
      injecting monospecific sera to those proteins into culture cells. Here we have
      used an antibody raised against an N-terminal peptide of the human autoantigen
      CENP-A to determine its function in mitosis and during cell cycle progression.
      Affinity-purified anti-CENP-A antibodies injected into the nucleus during the
      early replication stages of the cell cycle caused cells to arrest in interphase
      before mitosis. These cells showed highly condensed small nuclei, a granular
      cytoplasm and loss of their division capability. On the other hand,
      microinjection of nocodazole-blocked HeLa cells in mitosis resulted in the
      typical punctate staining pattern of CENP-A for centromeres during different
      stages of mitosis and apparently normal cell division. This was corroborated by
      time-lapse imaging microscopy analysis of mid-interphase-injected cells,
      revealing that they undergo mitosis and divide properly. However, a significant
      delay throughout the progression of mitotic stages was observed. These results
      suggest that CENP-A is involved predominantly in an essential interphase event at
      the centromere before mitosis. This may include chromatin assembly at the
      kinetochore coordinate with late replication of satellite DNA to form an active
      centromere.

PMID- 9914373
TI  - Decondensation of pericentric heterochromatin alters the sequence of centromere
      separation in mouse cells.
AB  - The centromeres of a genome separate in a sequential, nonrandom manner that is
      apparently dependent upon the quantity and quality of pericentric
      heterochromatin. It is becoming increasingly clear that the biological properties
      of a centromere depend upon its physicochemical makeup, such as its tertiary
      structure, and not necessarily on its particular nucleotide sequence. To test
      this idea we altered the physical state of the AT-rich pericentric
      heterochromatin of mouse with Hoechst 33258 (bis-benzimidazole) and studied a
      biological parameter, viz., sequence of separation. We report that an alteration
      in the physical state of heterochromatin, i.e., decondensation, is accompanied by
      aberrations in the pattern of centromere separation. The most dramatic effect
      seems to be on chromosomes with large blocks of heterochromatin. Many chromosomes
      with large blocks of heterochromatin that, in untreated cells, separate late tend
      to separate early. Decondensation with Hoechst 33258 does not seem to alter the
      sequence of separation of inactive centromeres relative to that of active
      centromeres. These data indicate that alteration in the physical parameters of
      the pericentric heterochromatin might dispose the centromeres to errors. It is
      likely that this aberration results from early replication of the pericentric
      heterochromatin associated with active centromeres.

PMID- 9914372
TI  - Assay of centromere function using a human artificial chromosome.
AB  - In order to define a functional human centromere sequence, an artificial
      chromosome was constructed as a reproducible DNA molecule. Mammalian telomere
      repeats and a selectable marker were introduced into yeast artificial chromosomes
      (YACs) containing alphoid DNA from the centromere region of human chromosome 21
      in a recombination-deficient yeast host. When these modified YACs were introduced
      into cultured human cells, a YAC with the alphoid DNA from the alpha21-I locus,
      containing CENP-B boxes at a high frequency and a regular repeat array,
      efficiently formed minichromosomes that were maintained stably in the absence of
      selection and bound CENP-A, CENP-B, CENP-C and CENP-E. The minichromosomes, 1-5
      Mb in size and composed of multimers of the introduced YAC DNA, aligned at
      metaphase plates and segregated to opposite poles correctly in anaphase.
      Extensive cytological analyses strongly suggested that the minichromosomes had
      not acquired host sequences and were formed in all cases by a de novo mechanism.
      In contrast, minichromosomes were never produced with a modified YAC containing
      alphoid DNA from the alpha21-II locus, which contains no CENP-B boxes and has a
      less regular sequence arrangement. We conclude that alpha21-I alphoid DNA can
      induce de novo assembly of active centromere/kinetochore structures on
      minichromosomes.

PMID- 9914374
TI  - GFP tagging reveals human Polo-like kinase 1 at the kinetochore/centromere region
      of mitotic chromosomes.
AB  - Polo-like kinases (Plks) have been implicated in various aspects of M-phase
      progression in organisms ranging from yeast to man. In vertebrates, Plks
      participate in centrosome maturation and spindle assembly, as well as the
      activation of the Cdk1/cyclin B complex. Moreover, Plks are required for the
      destruction of mitotic cyclins, indicating that they play an important role in
      the regulation of the ubiquitin-dependent proteolytic degradation machinery that
      controls exit from M-phase. Here, we have fused Green Fluorescent Protein (GFP)
      to the N-terminus of human Plk1, and expressed this chimeric construct in human
      cells. We found that GFP-Plk1 associates with centrosomes, the equatorial spindle
      midzone and the postmitotic bridge of dividing cells, confirming and extending
      previous results obtained with conventional immunofluorescence microscopy. In
      addition, however, we observed fluorescence emanating from the midbody between
      dividing cells, and from discrete dots associated with mitotic chromosomes. This
      latter staining pattern being reminiscent of centromeres, we performed double
      labeling experiments with antibodies against the centromeric marker CENP-B, and
      reexamined the subcellular localization of endogenous Plk1 using different
      fixation procedures. Our data clearly show that both GFP-tagged Plk1 and
      endogenous Plk1 associate with the kinetochore/centromere region of human mitotic
      chromosomes. This novel localization of Plk1 suggests that substrates and/or
      regulators of Plks may be found among kinetochore-associated proteins with
      important functions in chromosome segregation and/or spindle checkpoint
      mechanisms.

PMID- 9914375
TI  - Mouse polo-like kinase 1 associates with the acentriolar spindle poles, meiotic
      chromosomes and spindle midzone during oocyte maturation.
AB  - We have examined the dynamics of the localisation of the polo-like kinase 1
      (Plk1) during maturation of the mouse oocyte. Levels of Plk1 protein increase
      following germinal vesicle breakdown, at which time the enzyme begins to
      accumulate at discrete positions on the condensing chromosomes and, subsequently,
      at the poles of the meiotic spindle, which moves towards the cortex of the egg.
      Interestingly, at metaphase in both meiotic divisions, Plk1 shows a punctate
      localisation along the broad spindle poles. Moreover, the punctate distribution
      of Plk1 on the meiotic chromosomes appears at early anaphase to correspond to the
      centromeric regions. The protein relocates to the spindle midzone during late
      anaphase and then associates with the midbody at telophase. We have confirmed the
      specific pattern of immuno-localisation seen in fixed preparations by observing
      the distribution of Plk1 tagged with green fluorescent protein in living oocytes.
      We discuss the localisation of the enzyme in light of the structure of the
      spindle poles, which are known to lack centrioles, and the highly asymmetric
      nature of the meiotic divisions.

PMID- 9914376
TI  - The POLO kinase is required at multiple stages during spermatogenesis in
      Drosophila melanogaster.
AB  - The polo gene of Drosophila melanogaster is the founding member of the polo-like
      kinase family which is conserved among eukaryotes. POLO has been implicated in
      the organisation and function of the mitotic apparatus. Furthermore, POLO has
      been shown to be required for normal spermatogenesis. To characterize further the
      role of POLO in spermatogenesis, polo mutants were analysed by immunostaining
      with specific antibodies and phase contrast microscopy. Immunofluorescence shows
      that POLO localises to the centrosomes, the centromere/kinetochore and the
      spindle midzone. The meiotic phenotype of various mutant allelic combinations was
      also studied in detail. Observation of mutant live testes indicates cytological
      abnormalities in all meiotic cell types, including variable DNA content and
      multipolar spindles. Primary spermatocytes in polo mutant testes contain an
      abnormal DNA content, suggesting failure of chromosome segregation during gonial
      division. Immunostaining of polo mutant cells with alpha-tubulin shows several
      abnormalities of the meiotic spindle, including a significantly reduced central
      spindle. Our results suggest that polo has multiple functions during
      spermatogenesis.

PMID- 9914377
TI  - Interactions between mgr, asp, and polo: asp function modulated by polo and
      needed to maintain the poles of monopolar and bipolar spindles.
AB  - We describe genetic interactions between mutations in mgr, asp, and polo, genes
      required for the correct behaviour of the spindle poles in Drosophila. The
      phenotype of a polo1 mgr double mutant is more similar to mgr than polo1, but the
      frequency of circular monopolar figures (CMFs) seen with either mutant alone is
      additive, suggesting that the two gene products are required for independent
      functions in the formation of bipolar spindles. The aspE3 mgr double mutant
      arrests much earlier in development than either mutant alone, indicative of a
      strong block to cell proliferation. We discuss whether the lack of microtubular
      structures in these cells reflects an extended mitotic arrest, or if it is a more
      direct consequence of the double mutant combination. A polo1 aspE3 double mutant
      shows a dramatic synergistic increase in mitotic frequency. The loss of CMFs
      normally associated with the polo1phenotype suggests that the Asp microtubule
      associated protein is required to maintain the structure of spindle poles. We
      speculate that Asp protein might be a substrate for the serine-threonine protein
      kinase encoded by polo.

PMID- 9914378
TI  - Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their
      possible interaction in signalling cytokinesis.
AB  - TD-60 and INCENP are two members of the chromosome passenger protein family, and
      each has been suggested to play a role in the control of cytokinesis. Here we
      demonstrate by confocal immunofluorescence microscopy that TD-60 and INCENP
      distribute identically throughout the cell cycle. Both appear coordinately in G2
      phase nuclei and become concentrated at centromeres during prophase. TD-60 and
      INCENP both then leave the chromosome together during anaphase and redistribute
      to the spindle midzone, as do other chromosome passenger proteins, and traverse
      the entire equatorial diameter from cortex to cortex. By image overlay and pixel
      count analysis we show that TD-60 and INCENP are distinct among known chromosome
      passenger proteins in extending beyond the spindle to the cortex. Further, we
      show that the cytokinesis-associated protein kinase AIM-1 also shares this
      distribution property. We suggest that this redistribution is required to signal
      cytokinesis. TD-60 and INCENP also show identical localization in cells that exit
      mitosis in the presence of dihydrocytochalasin B (DCB), an inhibitor of actin
      assembly. Such cells can resume cleavage upon removal of DCB and in a recovery
      subpopulation that cleaves only on one side, these proteins both colocalize to
      the cortex only where a cleavage furrow forms. Given the coincident distribution
      of TD-60 and INCENP during both interphase and mitosis, we suggest that these
      proteins may cooperate, perhaps within a protein complex, in signalling
      cytokinesis. Such a mechanism, using chromosome passenger proteins, may ensure
      that cytokinesis occurs only between the separated chromatids, and only after
      they have segregated.

PMID- 9914379
TI  - Regulation of tubulin polypeptides and microtubule function: Luv1p [correction of
      Rki1p] interacts with the beta-tubulin binding protein Rbl2p.
AB  - Genetic analysis of microtubule functions in the yeast Saccharomyces cerevisiae
      suggests that cells manage the levels and activities of the tubulin polypeptides.
      These reactions may be involved in protein folding, formation of the heterodimer,
      and maintenance of the appropriate balance between alpha- and beta-tubulin. One
      protein involved in these functions is Rbl2p, which forms a complex with beta
      tubulin. Here we describe the identification of a novel yeast gene, LUV1
      [corrected], that interacts genetically with RBL2. Deletion of rki1 causes
      conditional defects in microtubule assembly and cell growth. Luv1p [corrected]
      can be isolated in a complex containing Rbl2p. The results support the existence
      of cellular mechanisms for regulating microtubule function through the tubulin
      polypeptides.

PMID- 9914380
TI  - Simultaneous inhibition of contractile ring and central spindle formation in
      mammalian cells treated with cytochalasin B.
AB  - In this work we have used the inhibitor of F-actin polymerisation cytochalasin B
      (Cyt B) to test the hypothesis that the contractile ring and the central spindle
      are mutually interdependent structures in mammalian mitotic cells. Double
      fluorescence staining of alpha-tubulin and F-actin was employed to analyse
      anaphase and telophase figures from asynchronously growing cultures and
      prometaphase-synchronised cells. Testing for the presence of the central spindle
      and contractile ring in human primary fibroblasts, human hepatoma cells and
      Chinese hamster cells after Cyt B treatment showed that both structures were
      simultaneously absent in over 60% of treated anaphases and 80% of telophases.
      Experiments on resumption of cytokinesis in cleavage-arrested cells further
      showed that Cyt B-treated human fibroblasts proceeded to cleavage within minutes
      after removal of the drug from the medium, concomitant with the re-formation of
      both cellular structures in cleaving cells. These data suggest that the presence
      of a correctly assembled contractile ring is essential for the formation and
      persistence of the central spindle during ana-telophase and provide further
      support for the idea of a strong co-operative interaction between these two
      structures during cytokinesis.

PMID- 9914381
TI  - Induction of diplochromosomes in mammalian cells by inhibitors of topoisomerase
      II.
AB  - Diplochromosomes, consisting of four chromatids lying side-by-side, instead of
      the normal two, are produced when cells go through two rounds of DNA replication
      without separation of chromatids. They are thus an indication of the failure of
      the normal chromosome separation mechanism. In the present experiments, induction
      of diplochromosomes by inhibitors of topoisomerase II (Topo II) was used to
      provide further evidence that Topo II is required for separation of daughter
      chromosomes. Actively growing cultures of CHO cells were treated with Colcemid,
      and separated into metaphase and interphase fractions, each of which was treated
      for 2 h with the Topo II inhibitor being tested. The cells were then cultivated
      in fresh medium without inhibitor for periods of between 18 and 44 h, and
      metaphase cells once again accumulated by treatment with Colcemid. Chromosome
      preparations were made in the standard way and stained with Giemsa. Up to 2,000
      metaphases were counted from each culture, and the proportion with
      diplochromosomes calculated. At appropriate concentrations, the Topo II
      inhibitors etoposide and mitoxantrone induced substantial levels of metaphases
      with diplochromosomes in cultures that had been treated when the cells were in
      interphase (up to 30% and 11%, respectively). Amsacrine, however, only produced a
      smaller proportion (4.7%) of metaphases with diplochromosomes after a much longer
      culture period following treatment. All the inhibitors caused severe chromosome
      damage. When used to treat metaphase cells, mitoxantrone and amsacrine only
      induced diplochromosomes after prolonged culture, although a small number of
      diplochromosomes were seen after etoposide treatment and a shorter period of
      culture. Results with cells treated in metaphase might indicate that Topo II is,
      in fact, not required for anaphase chromosome separation, although it is clearly
      important for segregation of newly replicated DNA.

PMID- 9914382
TI  - Segregational fidelity of chromosomes in human thyroid tumour cells.
AB  - Using fluorescence in situ hybridisation (FISH) we have analysed the
      segregational fidelity of all the human chromosomes during mitotic cell division.
      The losses and gains of chromosomes were analysed in human polyploid cell lines
      derived from a well-differentiated papillary thyroid cancer. These thyroid cells
      can be cultured for more than 300 population doublings. For the purpose of our
      study the polyploid nature of the cells may act as a protective buffer against
      the cell-lethal effects of the loss of individual chromosomes. To evaluate the
      role of the p53 gene product in maintaining the fidelity of chromosome
      segregation we compared the frequencies of chromosome loss and gain in cultures
      with wild-type p53 activity (K1E7neo3) and cultures transfected with plasmids
      expressing a mutant p53 product (K1E7scx6). Cultures were analysed for the
      presence of both structurally normal and rearranged chromosomes at both early and
      late passages. Cell cultures with defective p53 activity showed progressive
      chromosome loss from a median chromosome number of 87-97 to 75-86. Cell growth in
      cultures with wild-type p53 activity showed the loss of chromosomes 6, 7, and 8
      and the gain of 17 and 20. Cultures expressing mutant p53 activity showed the
      loss of chromosomes 2, 5, 14 and 17 and the gain of 4 and 22. The combination of
      defective p53 and growth resulted in further destabilisation with the additional
      losses of chromosomes 3, 11, 15, 16 and 21. Chromosomes 1, 9, 10, 12, 13, 18, 19,
      X and Y segregated stably under all the culture conditions as did the
      structurally rearranged marker chromosomes. The study has demonstrated variation
      in the fidelity of mitotic chromosome segregation and the influence of p53 gene
      activity upon the segregation of individual human chromosomes.

PMID- 9914383
TI  - Inhibition of the Mr 70,000 S6 kinase pathway by rapamycin results in chromosome
      malsegregation in yeast and mammalian cells.
AB  - The antifungal and immunosuppressive drug rapamycin arrests the cell cycle in G1
      phase in both yeast and mammalian cells. In mammalian cells, rapamycin
      selectively inhibits phosphorylation and activation of p70 S6 kinase (p70(S6K)),
      a protein involved in the translation of a subset of mRNAs, without affecting
      other known kinases. We now report that rapamycin causes chromosome
      malsegregation in mammalian and yeast cells. Chromosome malsegregation was
      determined by metaphase chromosome analysis of human lymphocytes and
      lymphoblasts, detection of CREST-positive micronuclei in human lymphoblasts and
      Chinese hamster embryonic fibroblast (CHEF) cells, and selection of doubly
      prototrophic cells in a specially constructed yeast strain. The number of ana
      telophases with displaced chromosomes and interphase and mitotic cells with an
      irregular number of centrosomes was also determined in CHEF cells. In quiescent
      mammalian cells (human lymphocytes and CHEF cells) induced with growth factor to
      re-enter the cell cycle, rapamycin was effective when cells were exposed at the
      time of p70(S6K) activation. In yeast, rapamycin was more effective when
      treatment was started in G1- than in G2-synchronized cells. Cells from ataxia
      telangiectasia (A-T) patients are characterized by chromosome instability and
      have recently been found to be resistant to the growth-inhibiting effect of
      rapamycin. We found that an A-T lymphoblastoid cell line was also resistant to
      the induction of chromosome malsegregation by rapamycin, but the level of
      spontaneous aneuploidy was higher than in normal cells. In yeast, the induction
      of chromosome malsegregation was dependent on the presence of a wild-type TUB2
      gene, encoding the beta-subunit of tubulin. The finding that rapamycin acts in
      different cell types and organisms suggests that the drug affects a conserved
      step important for proper segregation of chromosomes. One or more proteins
      required for chromosome segregation could be under the control of the rapamycin
      sensitive pathway.

PMID- 9914384
TI  - Aging and diethylstilbestrol-induced aneuploidy in male germ cells: a transgenic
      mouse model.
AB  - The incidence of aneuploidy in male germ cells was evaluated by analyzing extra
      marker chromosome(s) signal(s) in round and/or hook spermatids of transgenic
      mice. Two types of transgenic mice were used as models. The inserted foreign DNA
      (lambda-gt10LacZ shuttle vector and/or pSVc-myc plasmid) was located at the
      middle of the long arms of chromosome 2 (lambda DNA) and/or chromosome 8 (c-myc).
      The number of marker chromosomes present could easily be detected after
      fluorescence in situ hybridization (FISH) in testicular cells. The frequency of
      spontaneous aneuploidy of chromosome 2 was similar in round spermatids of lambda
      and lambda-myc mice. Differential involvement of chromosomes 2 and 8 was observed
      in both round and hook spermatids. The frequency of spontaneous aneuploidy in
      round spermatids was higher than that in hook spermatids. The frequency of
      aneuploidy of marker chromosomes was significantly higher in older mice (2 years
      old) than in younger ones. Diethylstilbestrol (DES)-induced aneuploidy was dose
      dependent, and was not influenced by the stage at which germ cells were treated
      with DES. These results demonstrate the usefulness of a transgenic mouse model
      for the study of aneuploidy in germ cells.

PMID- 9914385
TI  - Trichlorfon exposure, spindle aberrations and nondisjunction in mammalian
      oocytes.
AB  - Consumption of trichlorfon-poisoned fish by women in a small Hungarian village
      has been associated with trisomy resulting from an error of meiosis II in
      oogenesis. We therefore examined mouse oocytes exposed for 3 h during
      fertilization to 50 microg/ml trichlorfon. Spindle morphology was not visibly
      altered by the pesticide. Chromosomes segregated normally at anaphase II with no
      induction of aneuploidy. However, formation of a spindle was disturbed in many
      oocytes resuming meiosis I in the presence of trichlorfon. In spite of the
      spindle aberrations and the failure of bivalents to align properly at the
      equator, oocytes did not become meiotically arrested but progressed to metaphase
      II. At this stage, spindles were highly abnormal, and chromosomes were often
      totally unaligned, unattached or dispersed on the elongated and disorganized
      spindle. By causing spindle aberrations and influencing chromosome congression,
      trichlorfon appears, therefore, to predispose mammalian oocytes to random
      chromosome segregation, especially when they undergo a first division and develop
      to metaphase II during exposure. This is the first case in which environmentally
      induced human trisomy can be correlated with spindle aberrations induced by
      chemical exposure. Our observations suggest that oocytes may not possess a
      checkpoint sensing displacement of chromosomes from the equator at meiosis I and
      may therefore be prone to nondisjunction.

PMID- 9914386
TI  - Human sperm chromosome complements in chemotherapy patients and infertile men.
AB  - Our studies of human sperm karyotypes and interphase sperm analyzed by
      fluorescence in situ hybridization (FISH) have both yielded estimates of disomy
      frequencies of approximately 0.1% per chromosome with an overall aneuploidy
      frequency in human sperm of approximately 5%-6%. However, the distribution of
      aneuploidy in sperm is not even, as our data from sperm karyotypes and
      multicolour FISH analyses both demonstrate a significant increase in the
      frequency of aneuploidy for chromosome 21 and the sex chromosomes. We have
      studied men at increased risk of sperm chromosomal abnormalities including cancer
      patients and infertility patients. Testicular cancer patients were studied before
      and 2-13 years after chemotherapy (CT) with BEP (bleomycin, etoposide,
      cisplatin). Sperm karyotype analysis on 788 sperm demonstrated no significant
      difference in the frequency of numerical or structural chromosomal abnormalities
      post-CT vs pre-CT. Similarly, multicolour FISH analysis for chromosomes 1, 12,
      XX, YY and XY in 161,097 sperm did not detect any significant differences in the
      frequencies of disomy before and after treatment. However, recent evidence has
      suggested a significant increase in the frequency of disomy and diploidy during
      CT. We have found that infertile men, who would be candidates for
      intracytoplasmic sperm injection, have an increased frequency of chromosomally
      abnormal sperm karyotypes. Also, FISH analysis for chromosomes 1, 12, 13, 21, XX,
      YY and XY in 255,613 sperm demonstrated a significant increase in chromosomes 1,
      13, 21, and XY disomy in infertile men compared with control donors.

PMID- 9914387
TI  - Angiotensin II stimulation of Ca2+-channel current in vascular smooth muscle
      cells is inhibited by lavendustin-A and LY-294002.
AB  - Angiotensin II (AngII) is coupled to several important intracellular signaling
      pathways, and increases intracellular Ca2+. In vascular smooth muscle (VSM)
      cells, AngII is known to activate enzymes such as tyrosine protein kinase (Tyr
      PK), phospholipase C (PLC), protein kinase C (PKC), and phophatidylinositol-3
      kinase (PI-3-K). A non-receptor Tyr-PK, pp60(c-src), and PKC have been reported
      to stimulate the Ca2+ channels in VSM cells. However, less is known about AngII
      action on the voltage-gated Ca2+ channels. The Ca2+-channel currents of a
      cultured rat aortic smooth muscle cell line, A7r5, were recorded using whole-cell
      voltage clamp. Application of 50 nM AngII significantly increased the amplitude
      of Ba2+ currents through the voltage-gated Ca2+ channels (IBa) by 34. 5+/-9.1%
      (n=10) within 1 min. In the presence of lavendustin-A (5 microM), a selective
      inhibitor of Tyr-PK, AngII failed to stimulate IBa (n=5). AngII stimulation of
      IBa was also prevented by (5 microM) LY-294002, an inhibitor of PI-3-K (n=5). In
      contrast, H-7 (30 microM), an inhibitor of PKC, did not prevent the effect of
      AngII on IBa (n=6). These results suggest that AngII may stimulate the Ca2+
      channels of VSM cells through Tyr-PK and PI-3-K under conditions that probably
      exclude participation of PK-C.

PMID- 9914388
TI  - A nutrient-regulated cytosolic calcium oscillator in endocrine pancreatic
      glucagon-secreting cells.
AB  - We investigated the influence of nutrients on spontaneous cytosolic calcium
      oscillations in InR1-G9 glucagonoma cells, a model for pancreatic alpha-cells.
      The oscillations depended on calcium release from stores and on calcium influx,
      partly through voltage-dependent calcium channels. Oscillations required the
      presence of at least 1 mM glucose, 50 microM alanine, or 50 microM glutamine, but
      were terminated by higher nutrient concentrations (40 mM glucose, or above 2 mM
      alanine or glutamine). The effects depended on the metabolism of the nutrients.
      Glutamine and alanine hyperpolarized the cells. This effect was inhibited
      (glutamine) or attenuated (alanine) by 1 mM ouabain. Our findings suggest that
      [Ca2+]i regulation in alpha-cells is dominated by slow oscillations induced by a
      lack of metabolic energy, resulting in decreased calcium export and storage, as
      well as increased calcium influx, partly due to depolarization caused by reduced
      sodium pump activity. These processes, leading to an elevated cytosolic calcium
      concentration, may mediate oscillations by calcium-induced calcium release from
      intracellular stores.

PMID- 9914389
TI  - Role of PKC in the effects of alpha1-adrenergic stimulation on Ca2+ transients,
      contraction and Ca2+ current in guinea-pig ventricular myocytes.
AB  - The effects of alpha1-adrenoceptor stimulation on intracellular Ca2+ transients,
      contractility and L-type Ca2+ current (ICa,L) were studied in single cells
      isolated from ventricles of guinea-pig hearts. The aim of our study was to
      elucidate the mechanisms of the positive inotropic effect of alpha1-adrenergic
      stimulation by focussing on the role of protein kinase C (PKC). Phenylephrine, an
      alpha1-adrenergic agonist, at concentrations of 50-100 microM elicited a biphasic
      inotropic response: a transient negative inotropic response (22.9+/-6.0% of
      control) followed by a sustained positive inotropic response (61.0+/-8.4%, mean+/
      SE, n=12). The Ca2+ transient decreased by 10.2+/-3.9% during the negative
      inotropic phase, while it increased by 67.7+/-10% (n=12) during the positive
      inotropic phase. These effects were inhibited by prazosin (1 microM), a alpha1
      adrenergic antagonist. Phenylephrine increased the ICa,L by 60.8+/-21% (n=5)
      during the positive inotropic phase. To determine whether activation of PKC is
      responsible for the increases in Ca2+ transients, contractile amplitude and ICa,L
      during alpha1-adrenoceptor stimulation, we tested the effects of 4beta-phorbol 12
      myristate 13-acetate (PMA), a PKC activator, and of bisindolylmaleimide I
      (GF109203X) and staurosporine, both of which are PKC inhibitors. PMA mimicked
      phenylephrine's effects on Ca2+ transients, contractile amplitude and ICa,L. PMA
      (100 nM) increased the Ca2+ transient, contractile amplitude and ICa,L by 131+/
      17%, 137+/-25% (n=8), and 81.1+/-26% (n=5), respectively. Prior exposure to
      GF109203X (1 microM) or staurosporine (10 nM) prevented the phenylephrine-induced
      increases in Ca2+ transients, contractile amplitude and ICa,L. Our study suggests
      that during alpha1-adrenoceptor stimulation increase in ICa,L via PKC causes an
      increase in Ca2+ transients and thereby in the contractile force of the
      ventricular myocytes.

PMID- 9914390
TI  - Gating of cx46 gap junction hemichannels by calcium and voltage.
AB  - Connexin 46 (cx46), when expressed in Xenopus oocytes, not only forms typical gap
      junction channels between paired cells but also forms open gap junction
      hemichannels in the plasma membrane of single cells. The gap junction
      hemichannels share properties with complete gap junction channels in terms of
      permeability and gating. Here we characterize the gate that closes hemichannels
      in response to increased calcium concentration with whole-cell and single-channel
      records. The channels close within a narrow range of extracellular calcium
      concentrations (1-2 mM) which includes the calcium concentration prevailing in
      the primary site of cx46 expression, the lens. The effect of calcium on the
      channels is determined by voltage. A cysteine mutant of cx46, cx46L35C, was used
      to determine the localization of the gate. Experimental evidence suggests that
      position 35 is pore lining. The localization protocol tests the accessibility of
      position 35 for thiol reagents applied extra- or intracellularly to the channel
      closed by calcium. Channel closure by calcium excluded the thiol reagent from the
      outside but not from the inside. Consequently, the gate results in a regional
      closure of the pore and it is located extracellular to the position 35 of cx46.
      The present data also suggest that the cx46 gap junction hemichannel may exert a
      physiological function in the lens. Considering the association of calcium with
      cataract formation, it is feasible that misregulation of cx46 gap junction
      hemichannels could be a cause for cataract.

PMID- 9914391
TI  - Na+-dependent regulation of the free Mg2+ concentration in neuropile glial cells
      and P neurones of the leech Hirudo medicinalis.
AB  - To investigate the Mg2+ regulation in neuropile glial (NG) cells and pressure (P)
      neurones of the leech Hirudo medicinalis the intracellular free Mg2+ ([Mg2+]i)
      and Na+ ([Na+]i) concentrations, as well as the membrane potential (Em), were
      measured using Mg2+- and Na+-selective microelectrodes. The mean steady-state
      values of [Mg2+]i were found to be 0.91 mM (mean Em=-63.6 mV) in NG cells and
      0.20 mM (mean Em=-40.6 mV) in P neurones with a [Na+]i of 6.92 mM (mean Em=-61.6
      mV) and 7.76 mM (mean Em=-38.5 mV), respectively. When the extracellular Mg2+
      concentration ([Mg2+]o) was elevated, [Mg2+]i in P neurones increased within 5-20
      min whereas in NG cells a [Mg2+]i increase occurred only after long-term exposure
      (6 h). After [Mg2+]o was reduced back to 1 mM, a reduction of the extracellular
      Na+ concentration ([Na+]o) decreased the inwardly directed Na+ gradient and
      reduced the rate of Mg2+ extrusion considerably in both NG cells and P neurones.
      In P neurones Mg2+ extrusion was reduced to 15.4% in Na+-free solutions and to
      6.0% in the presence of 2 mM amiloride. Mg2+ extrusion from NG cells was reduced
      to 6.2% in Na+-free solutions. The results suggest that the major [Mg2+]i
      regulating mechanism in both cell types is Na+/ Mg2+ antiport. In P neurones a
      second, Na+-independent Mg2+ extrusion system may exist.

PMID- 9914392
TI  - The effects of oxytocin on the pattern of electrical propagation in the isolated
      pregnant uterus of the rat.
AB  - In the isolated pregnant myometrium of the rat, the pattern of propagation was
      investigated by recording simultaneously from 240 different extracellular sites
      while the contraction of the tissue was recorded isometrically. Analysis of all
      recorded electrograms allowed the two-dimensional spread of activity in the
      myometrium to be reconstructed. From these activation maps, the conduction
      velocities were measured in the longitudinal, oblique and transversal directions.
      At low concentrations (10(-9 )and 5x10(-9) M), oxytocin significantly increased
      the frequency and duration of electrical bursts and the average spike intervals,
      without affecting the homogeneity of action potential propagation, concomitant
      with a significant increase in the amplitude of contractions. At high
      concentrations (10(-8) and 5x10(-8) M), oxytocin induced conduction blocks and
      the size of inexcitable areas was increased, concomitantly with an increase in
      muscle contractures. In contrast, the conduction velocities in the longitudinal,
      oblique and circular directions were not influenced by oxytocin at any
      concentrations.

PMID- 9914393
TI  - Spontaneous changes in acetylcholine receptor and calcium leakage activity in
      cell-attached patches from cultured dystrophic myotubes.
AB  - Calcium leakage activity (CLA) was recorded in association with acetylcholine
      receptor (AChR) activity in cell-attached patches from cultured nondystrophic and
      dystrophic (mdx) myotubes. Cell-attached recordings from dystrophic myotubes
      exhibited spontaneous transitions in the activity pattern that were characterized
      by an instability of AChR function and a decrease in the frequency of AChR
      events. Recordings from nondystrophic myotubes could be maintained for similar
      time periods without observing any consistent changes in the distribution of CLA
      and AChR events, thus indicating that the conditions of the experiment were not
      conducive to developing AChR instability or desensitization in nondystrophic
      myotubes. In dystrophic myotubes, the decrease in AChR event frequency was
      associated with an increase in small-conductance events which had the
      characteristics of CLA, and the subsequent acquisition of an inside-out patch
      appeared to restore the AChR activity. Examination of baseline current-voltage
      relationships indicated that dystrophic and nondystrophic patches exhibited the
      same general pattern of seal maturation with temporal increases in the total
      patch circuit resistance. These results are discussed in relation to the AChR
      aggregation hypothesis, which proposes that the absence of dystrophin leads to
      abnormal AChR-cytoskeletal interactions and CLA that can be reversed by removing
      the influence of intracellular signal transduction enzymes that aggregate and
      stabilize AChR clusters.

PMID- 9914394
TI  - Expression environment determines K+ current properties: Kv1 and Kv4 alpha
      subunit-induced K+ currents in mammalian cell lines and cardiac myocytes.
AB  - Voltage-gated K+ channel (Kv) pore-forming (alpha) subunits of the Kv1 and Kv4
      subfamilies have been cloned from heart cDNA libraries, and are thought to play
      roles in the generation of the transient outward K+ current, Ito. Heterologous
      expression of these subunits in Xenopus oocytes, however, reveals K+ currents
      that are quite distinct from Ito. In the experiments here, the detailed time- and
      voltage-dependent properties of the currents expressed in mammalian cell lines
      and in cardiac myocytes by Kv1.4 and Kv4.2 were examined and compared to previous
      findings in studies of oocytes, as well as to Ito characterized in various
      myocardial cells. As in oocytes, expression of Kv1.4 in HEK-293, Ltk- or neonatal
      rat ventricular cells reveals rapidly activating K+ currents. In contrast to the
      currents in oocytes, however, there are two components of inactivation of the
      Kv1.4-induced currents in mammalian cells, and both components are significantly
      slower in myocytes than in either HEK-293 or Ltk- cells. In addition, in all
      three cell types, recovery of Kv1.4 from steady-state inactivation is very slow,
      proceeding with mean time constants in the range of 6-8 s. The properties of
      Kv4.2-induced currents also vary with cell type and, importantly, the rates of
      activation, inactivation and recovery from inactivation are significantly faster
      in mammalian cells than in Xenopus oocytes. In HEK-293, Chinese hamster ovary
      (CHO) and neonatal rat ventricular cells, for example, the currents recover from
      steady-state inactivation with mean (+/-SD) time constants of 153+/-32 (n=12),
      245+/-112 (n=10) and 86+/-38 (n=11) ms, respectively; therefore, recovery
      proceeds 5-10 times faster than observed for Kv4.2 in oocytes. These results
      emphasize the importance of the cellular expression environment in efforts to
      correlate endogenous K+ currents with heterologously expressed K+ channel
      subunits. In addition, the finding that Kv alpha subunits produce distinct K+
      currents in different cells suggests that cell-type-specific associations with
      endogenous Kv alpha or accessory beta subunits and/or post-translational
      processing play roles in determining the properties of functional K+ channels.

PMID- 9914395
TI  - The effect of phosphate on the relaxation of frog skeletal muscle.
AB  - The effect of phosphate on the relaxation of isometrically contracting single
      skinned fibres from the semitendinosus muscle of the frog Rana temporaria has
      been investigated using laser pulse photolysis of the photolabile caged calcium
      chelator diazo-2 to rapidly reduce the Ca2+ (<2 ms) within the fibre and produce
      >90% relaxation of force. Relaxation occurred in two phases - an initial linear
      shoulder which lasted approximately 20 ms followed by a double-exponential phase
      which gave two rate constants, k1 (43.4+/-1. 8 s-1, mean +/-SEM, n=14) and k2
      (15.6+/-0.3 s-1, mean +/-SEM, n=14) at 12 degreesC. Increased phosphate
      concentrations did not affect the linear phase, but slowed the double-exponential
      phase following photolysis of diazo-2 in a dose-dependent fashion (k50= 0.9 mM
      for k1, 1.15 mM for k2). Reducing the concentration of contaminating phosphate
      (from 640 microM to 100 microM) led to an increase in the rate of the double
      exponential phase (k1=67.1+/-4.4 s-1, k2=19.7+/-0. 6 s-1, mean +/-SEM, n=12).
      Time-resolved measurements of sarcomere length during relaxation, both in control
      fibres and in the presence of a raised phosphate concentration, reveal a <2%
      change throughout the whole relaxation transient, and less than 0.1% at the end
      of the linear phase. This finding implies that gross changes in sarcomere length
      do not contribute to the decay of the relaxation transient seen upon diazo-2
      photolysis. Our results suggest that cross-bridges in states prior to phosphate
      release are already committed to force generation and must relax by releasing
      phosphate, rather than by a reversal of the force-generating step to a weakly
      bound, low-force phosphate-bound state. These findings also indicate that an
      increase in the phosphate concentration within muscle fibres plays an important
      part in the slowing of relaxation observed in skeletal muscle fatigue and that
      the relaxation transients observed upon diazo-2 photolysis represent a
      disengagement of the cross-bridges.

PMID- 9914396
TI  - Antisense oligodeoxynucleotides of sulfonylurea receptors inhibit ATP-sensitive
      K+ channels in cultured neonatal rat ventricular cells.
AB  - To identify the functional sulfonylurea receptor (SUR), a subunit of the
      adenosine 5'-triphosphate (ATP)-sensitive K+ (KATP) channels, in neonatal rat
      ventricular cells, such cells in primary culture were treated for 6 days with
      antisense (AS) oligodeoxynucleotides (ODNs) complementary to the mRNA for SURs.
      For quantification, single-channel (inside-out patches) and whole-cell currents
      were measured using the patch-clamp technique. The maximal KATP currents (at 0
      mV) induced by metabolic inhibition were 48.9+/-2.8 pA/pF in control (n=48),
      34.3+/-3.5 pA/pF in AS-SUR1 (n=21, P<0.05 vs control), and 23.5+/-3.4 pA/pF in AS
      SUR2 (n=17, P<0.01 vs control). As a control, scramble oligonucleotides had no
      effect. The fast Na+ current and inward-rectifying K+ current were not affected
      by AS-SURs. Treatment with both AS-SUR1 and AS-SUR2 had no additive effects on
      inhibition of KATP currents compared with AS-SUR2 alone. The single-channel
      conductance, open probability, and kinetics (in ATP-free solution) were not
      significantly different between control, AS-SUR1, and AS-SUR2. These results
      suggest that treatment with AS-ODN for SUR1 or SUR2 reduced the number of
      functional KATP channels. Furthermore, in four out of seven control cells tested,
      outward K+ currents were stimulated by diazoxide, which is a potent K+ channel
      opening drug for the constructed SUR1/Kir6.2 and SUR2B/Kir6.2 channels, but not
      for the SUR2A/Kir6.2 channel. Therefore, in neonatal rat ventricular cells, both
      SUR2 and SUR1 subtypes could be integral components of the functional KATP
      channels. The larger population of KATP channels may be constructed with SUR2,
      whereas a smaller population may be constructed with a combination of SUR1 and
      SUR2.

PMID- 9914398
TI  - Effect of caffeine on K+ efflux in frog skeletal muscle.
AB  - The exposure of frog skeletal muscle to caffeine (3-4 mM) generates an increase
      of the K+ (42K+) efflux rate coefficient (kK,o) which exhibits the following
      characteristics. First it is promoted by the rise in cytosolic Ca2+ ([Ca2+]i),
      because the effect is mimicked by ionomycin (1.25 microM), a Ca2+ ionophore.
      Second, the inhibition of caffeine-induced Ca2+ release from the sarcoplasmic
      reticulum (SR) by 40 microM tetracaine significantly reduced the increase in kK,o
      (DeltakK,o). Third, charybdotoxin (23 nM), a blocker of the large-conductance
      Ca2+-dependent K+ channels (BKCa channels) reduced DeltakK,o by 22%. Fourth,
      apamin (10 nM), a blocker of the small-conductance Ca2+-dependent K+ channels
      (SKCa channels), did not affect DeltakK,o. Fifth, tolbutamide (800 microM), an
      inhibitor of KATP channels, reduced DeltakK,o by about 23%. Sixth, Ba2+, a
      blocker of most K+ channels, did not preclude the caffeine-induced DeltakK,o.
      Seventh, omitting Na+ from the external medium reduced DeltakK,o by about 40%.
      Eight, amiloride (5 mM) decreased DeltakK,o by 65%. It is concluded that the
      caffeine-induced rise of [Ca2+]i increases K+ efflux, through the activation of:
      (1) two channels (BKCa and KATP) and (2) an external Na+-dependent amiloride
      sensitive process.

PMID- 9914397
TI  - Regulation of ionic currents by protein kinase A and intracellular calcium in
      outer hair cells isolated from the guinea-pig cochlea.
AB  - Two prominent potassium currents, termed IK and IK,n, and a cation current are
      found in outer hair cells (OHCs) of the guinea-pig cochlea. We report here whole
      cell recordings which indicate that the currents are regulated by intracellular
      factors. 8-bromo-cAMP (500 microM), a membrane-permeable cAMP analogue, activated
      potassium currents in OHCs in both apical and basal turns of the cochlea. In OHCs
      from the cochlear apex, the drug effect was largest at potentials positive to -40
      mV, indicating IK as the target. In short cells from the cochlear base, both IK
      and IK,n were affected. The effects of 8-bromo-cAMP could be blocked by the
      presence of 1 microM H-89 (a protein kinase A inhibitor) in the patch pipette
      solution. Extracellular application of 10 nM okadaic acid, a protein phosphatase
      inhibitor, also activated both potassium currents. Currents were also modulated
      by intracellular calcium. IK was activated in long cells by photorelease of
      calcium from the caged compound nitr5. Cation current activation required calcium
      release by photolysis of DM-nitrophen, a compound releasing more calcium. The
      results show that OHC potassium channels are regulated by background
      phosphorylation through protein kinase A and dephosphorylation by protein
      phosphatase. Cellular calcium also activates IK and the cation channel, but with
      different sensitivities.

PMID- 9914399
TI  - Identification of two arginase isoenzyme activities along the nephron of Meriones
      shawi.
AB  - Conflicting theories on the existence of several renal arginase isoenzymes remain
      in debate. Because the activity of arginase is high in two embryologically
      different nephron segments of the Meriones shawi kidney, namely the cortical
      (CPST) and medullary (OSPST) proximal straight tubule and the outer medullary
      collecting duct (OMCD), we postulate that these nephron segments may contain
      different isoforms. Isolated nephron segments were dissected from collagenase
      treated kidneys. Tubules were permeabilized with Triton X-100 (0.25%) and
      incubated with increasing Arg concentrations to characterize the arginase
      activity. The results were as follows: (1) in OMCD, one arginase isoform (E1),
      characterized by a high Arg affinity (1.160 mM), was present; (2) in CPST, two
      arginase isoforms were discovered - one, E1, had a similar Km (1.407 mM) to that
      found in OMCD whereas the other (E2) had a low affinity for Arg (Km =18.8 mM);
      and (3) in OSPST, two isoenzymes were present - E1 which had a Km of 1.478 mM and
      the second isoform that we named E2 which had a Km of 9.07 mM. In addition,
      arginase located in CPST and OMCD was strongly inhibited by Orn and Lys. The Ki
      value for Lys varied between 1.635 and 2.288 mM. Therefore, this work
      demonstrates that two arginase isoforms are present in the kidney of Meriones
      shawi. Isoform E1 is present in the proximal tubule and the collecting duct
      whereas isoform E2 is restricted to the proximal tubule.

PMID- 9914400
TI  - Differential sensitivity of myosin-heavy-chain-typed fibers to distinct
      aggregates of nerve-mediated activation.
AB  - We studied the regulatory effects of nerve-mediated activity on the early
      expression of embryonic and adult myosin heavy chains (MHC) within inactive
      though still innervated rat plantaris and soleus muscle fibers. To this end, we
      stimulated motor nerves that were quiescent following treatment with tetrodotoxin
      (TTX) with paradigms designed to partition the influence of neural activation
      frequency and assessed the selective expression and accumulation of MHCs within
      muscle fibers using an array of specific antibodies. We show rapid de novo
      expression of IIx MHC within select soleus fibers in response to high-frequency
      activation for more than 0.01% of daily time. High-frequency aggregates were also
      the most effective in preventing the TTX-induced reexpression of embryonic MHCs
      within specific fibers. Only configurations that included high-frequency trains
      for more than 0.01% of daily time or combined with 10 Hz stimulation preserved
      the size of select fibers, used as a measure of the net cellular content of MHC.
      The effectiveness of this preservation varied according to the muscle type and
      MHC expressed, and, in a subset of fibers, was influenced by contractile loading
      status. Our results demonstrate that distinct subsets of MHC-typed fibers are
      differentially sensitive to the neural activation cues mediating the cellular
      expression of these proteins.

PMID- 9914401
TI  - Action-potential-like depolarizations relieve opioid inhibition of N-type Ca2+
      channels in NG108-15 cells.
AB  - The ability of action-potential-like waveforms (APWs) to attenuate opioid-induced
      inhibition of N-type Ca2+ channels was investigated in the neuroblastoma x glioma
      cell line NG108-15 using whole-cell voltage clamp methods. In in vitro
      differentiated NG108-15 cells, the opioid agonist [d-ala2]-methionine-enkephalin
      (DAME) reversibly decreased omega-conotoxin-GVIA-sensitive Ba2+ currents (N-type
      currents). Agonist-mediated inhibition of N-type currents could be transiently
      relieved by strong unphysiological depolarizing prepulses to +80 mV
      (facilitation). Significant facilitation was also achieved by conditioning the
      cell with a train of 15 APWs, which roughly mimicked physiological action
      potentials (1- to 6-ms-long depolarizations to +30 mV from a holding potential of
      -40 mV). The APW-induced facilitation depended on both conditioning pulse
      frequency and duration. Summation of the disinhibition produced by each APW was
      possible because reinhibition following repolarization to -40 mV was a much
      slower process (tau=88 ms) than the onset of facilitation at +80 mV (tau=7 ms).
      These results provide evidence that N-type Ca2+ channel facilitation may be a
      physiologically relevant process, and suggest that neuronal firing may relieve
      agonist-induced inhibition of N-type currents to an extent depending on both the
      shape of action potentials and the frequency of firing.

PMID- 9914403
TI  - Role of a Ca2+-activated K+ current in the maintenance of resting membrane
      potential of isolated, human, saphenous vein smooth muscle cells.
AB  - Calcium-activated potassium currents were studied in dissociated smooth muscle
      cells from human saphenous vein (HSV) using the patch-clamp technique in the
      whole-cell configuration. The average measured resting membrane potential (Vm)
      was -41+/-2 mV (n=39), when the cells were dialysed with an intracellular pipette
      solution (IPS) containing 0.1 mM ethyleneglycol-bis(beta-aminoethylether)-N,N,N',
      N'-tetraacetic acid (EGTA) (IPS-0.1 mM EGTA). When the EGTA concentration was
      increased to 10 mM (IPS-10 mM EGTA) Vm became significantly less negative: -13+/
      2 mV (n=23, P<0.05). These results suggest that 10 mM EGTA reduces a calcium
      dependent current involved in the maintenance of Vm. Depolarizing voltage steps
      up to +60 mV from holding potentials of -60 mV resulted in large (1-10 nA) time-
      and voltage-dependent outward currents. The amplitudes of total whole-cell
      current densities measured at voltages above -20 mV were significantly greater in
      the cells dialysed with IPS-0.1 mM EGTA than in those dialysed with IPS-10 mM
      EGTA. In the cells dialysed with IPS-0.1 mM EGTA, 0.1 mM tetraethylammonium
      chloride (TEA) and 50 nM iberiotoxin (IBTX), which selectively block large
      conductance Ca2+-activated potassium channels (BKCa), diminished the total
      current recorded at +60 mV by 45+/-14% (P<0.05, n=5) and 50+/-6% (n=8, P<0.05),
      respectively. These blockers at the same concentrations did not affect the total
      current in cells dialysed with IPS-10 mM EGTA. When tested on intact HSV rings,
      both 0.1 mM TEA and 50 nM IBTX elicited vessel contraction. We conclude that BKCa
      channels present in HSV smooth muscle cells contribute to the maintenance of the
      Vm and sustain a significant portion of the total voltage-activated, outward
      current. Finally, BKCa channels appear to play a significant role in the
      regulation of HSV smooth muscle contractile activity.

PMID- 9914402
TI  - Renin secretion from permeabilized juxtaglomerular cells requires a permeant
      cation.
AB  - The cytosolic concentration of chloride correlates directly with renin secretion
      from renal juxtaglomerular granular (JG) cells. In the present study, the
      mechanism by which chloride stimulates renin release was investigated in a
      preparation of permeabilized rat glomeruli with attached JG cells. An isosmotic
      increase in the concentration of chloride by 129 mM stimulated renin release 16-
      to 20-fold. Substitution of K+ by the impermeant cation N-methyl-d-glucamine
      (NMDG) abolished this response, while substitution with Na+ caused marginal
      inhibition. Substitution with Cs+ had no effect. Addition of sucrose, which
      permeates the secretory granules poorly, also abolished the stimulation of renin
      secretion by KCl. The response to KCl was not affected by K+-channel antagonists
      or by agonists of K+ channels. Chloride channel blockers were also without effect
      on the secretory response to KCl. When the ATP concentration was lowered from 1
      to 0.1 mM renin release was stimulated, while an increase in the ATP
      concentration from 1 to 5 mM had no effect. Blockers of ATP-sensitive (KATP)
      channels did not modify the response to chloride. The present data suggest that
      chloride stimulates renin release after entry of KCl into the renin secretory
      granules which results in swelling and release of renin.

PMID- 9914404
TI  - Monte carlo simulation of vesicular release, spatiotemporal distribution of
      glutamate in synaptic cleft and generation of postsynaptic currents.
AB  - The release of vesicular glutamate, spatiotemporal changes in glutamate
      concentration in the synaptic cleft and the subsequent generation of fast
      excitatory postsynaptic currents at a hippocampal synapse were modeled using the
      Monte Carlo method. It is assumed that glutamate is released from a spherical
      vesicle through a cylindrical fusion pore into the synaptic cleft and that S
      alpha-amino-3-hydroxy -5-methyl-4-isoxazolepropionic acid (AMPA) receptors are
      uniformly distributed postsynaptically. The time course of change in vesicular
      concentration can be described by a single exponential, but a slow tail is also
      observed though only following the release of most of the glutamate. The time
      constant of decay increases with vesicular size and a lower diffusion constant,
      and is independent of the initial concentration, becoming markedly shorter for
      wider fusion pores. The cleft concentration at the fusion pore mouth is not
      negligible compared to vesicular concentration, especially for wider fusion
      pores. Lateral equilibration of glutamate is rapid, and within approximately 50
      micros all AMPA receptors on average see the same concentration of glutamate.
      Nevertheless the single-channel current and the number of channels estimated from
      mean-variance plots are unreliable and different when estimated from rise- and
      decay-current segments. Greater saturation of AMPA receptor channels provides
      higher but not more accurate estimates. Two factors contribute to the variability
      of postsynaptic currents and render the mean-variance nonstationary analysis
      unreliable, even when all receptors see on average the same glutamate
      concentration. Firstly, the variability of the instantaneous cleft concentration
      of glutamate, unlike the mean concentration, first rapidly decreases before
      slowly increasing; the variability is greater for fewer molecules in the cleft
      and is spatially nonuniform. Secondly, the efficacy with which glutamate produces
      a response changes with time. Understanding the factors that determine the time
      course of vesicular content release as well as the spatiotemporal changes of
      glutamate concentration in the cleft is crucial for understanding the mechanism
      that generates postsynaptic currents.

PMID- 9914406
TI  - Differential down-regulation of beta3-adrenergic receptor mRNA and signal
      transduction by cold exposure in brown adipose tissue of young and senescent
      rats.
AB  - Diminished beta3 adrenergic-stimulated thermogenesis in brown adipose tissue
      (BAT) in senescent rats is restored by a short period of cold exposure. To
      investigate if the mechanism of this restoration involves preferential up
      regulation of beta3-adrenergic signal transduction in senescent compared with
      young rats, we examined the steady state levels of beta3-adrenergic receptor
      messenger ribonucleic acid (beta3AR mRNA) and the dose/response relationship for
      the activation of adenylyl cyclase by the selective beta3-adrenergic agonist, BRL
      37344 in BAT membranes from young and senescent rats with or without 2 days cold
      exposure at 8 degrees C. beta3AR mRNA declined by 30% with age and by 60% with
      cold exposure in young rats. In contrast, cold exposure did not down-regulate
      beta3AR mRNA in senescent rats. BRL 37344-stimulated adenylyl cyclase activity
      was 38% less in senescent rats and was desensitized by cold exposure decreasing
      maximum stimulation by 78% and increasing, the dissociation constant 2.5-fold.
      Cold exposure decreased BRL 37344-stimulated adenylyl cyclase activity to a
      lesser extent in senescent rats (50%), such that the activity was similar in cold
      exposed young and old rats. These data indicate that although cold exposure did
      not, as we hypothesized, up-regulate beta3-adrenergic signal transduction in the
      senescent rats, cold exposure preferentially down-regulated beta3AR mRNA and
      beta3AR-mediated adenylyl cyclase in the young compared with senescent rats.

PMID- 9914405
TI  - Effect of cyclothiazide on spontaneous miniature excitatory postsynaptic currents
      in rat hippocampal pyramidal cells.
AB  - Spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded
      from the CA1 region of slices using the whole-cell patch-clamp technique.
      Cyclothiazide (0.1 mM), a complete blocker of desensitization of (S)-alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) channels, was applied to
      determine the changes in amplitude and kinetics of mEPSCs occurring with complete
      suppression of desensitization. The amplitude of mEPSC (A) was not affected
      significantly by cyclothiazide, but both the rise (taur) and the decay time
      (taud) were consistently increased (from 2.3 to 6.5 ms and from 9.9 to 22.2 ms
      respectively). The amplitude dependence of both taud and taur became much
      greater, but there was no upward shift of the best-fitting lines. The slopes of
      the control best-fitting lines were (+/-SD; ms/pA; n=5) 0.39+/-0.05 for taud:A
      and 0.12+/-0.07 for taur:A, but, in the presence of cyclothiazide, the
      corresponding slopes were much steeper (2.1+/-0.60 and 0.68+/-0. 21; holding
      potential was -50 mV and temperature 32 degreesC). These changes, which were slow
      to develop, suggest that cyclothiazide blocks AMPA receptor channel
      desensitization, whilst having no effect on the closing rate of AMPA channels.
      Judging by the extent of change, the speed of diffusion of glutamate in the
      synaptic cleft is probably similar to that in water. In conclusion, this study
      provides evidence that: (1) under control conditions, desensitization of AMPA
      channels plays a major role in shaping the time course of synaptic currents in
      CA1; and (2) cyclothiazide prolongs their time course solely by abolishing
      desensitization.

PMID- 9914407
TI  - NH4+ conductance in Xenopus laevis oocytes.II. Effect Of hypoosmolality.
AB  - Superfusing Xenopus laevis oocytes with NH4Cl (10 mmol/l, pH 7.5) resulted in an
      inward current at a clamp potential of -70 mV. In paired experiments (n=22), the
      NH4Cl-induced peak current was -293+/-94 nA, under control conditions
      (osmolality: 240 mosmol/kg), and rose to -523+/-196 nA when osmolality was
      reduced to 144 mosmol/kg. In parallel with the rise in NH4Cl-induced inward
      current, membrane conductance at -70 mV doubled and the zero-current potential
      changed from +3.3+/-9.4 mV to -22.0+/-8.0 mV (n=22) in the presence of NH4Cl
      during exposure to a hypoosmolar solution. In the absence of NH4Cl, oocytes
      responded to hypoosmolality with a shift in zero-current potential to more
      negative values and an increased conductance which became partially sensitive to
      isosorbiddinitrate (ISDN), suggesting the activation of a volume-sensitive K+
      channel. Membrane conductance in the presence of NH4Cl was decreased by ISDN to
      similar extents under isoosmolal and hypoosmolal conditions, indicating that NH4+
      enters the oocytes through a volume-sensitive conductance separate from the ISDN
      sensitive K+ channel.

PMID- 9914408
TI  - Expression of the epithelial sodium channel (ENaC) during ontogenic
      differentiation of the renal cortical collecting duct epithelium.
AB  - The NaCl-reabsorbing collecting duct epithelium develops by budding and branching
      of the embryonic ureter. The expression of Na+ channels during this branching
      morphogenesis was studied in the outermost branches of rat ureteric buds (UB;
      embryonic day E15 to postnatal day P6) and in cortical collecting ducts (CCD;
      days P7-P28) in primary monolayer culture. Expression of both Na+ channel mRNA
      and of Na+-selective membrane conductance were estimated by quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) and by patch-clamp recording,
      respectively. UB and CCD uniformly represented a principal-like cell type in
      culture. Messenger RNA encoding the alpha-ENaC subunit was detected in oligo-dT
      primed cDNA (5 ng) of embryonic UB cells (E15-17) after 30 PCR cycles. The
      abundance of alpha-ENaC mRNA, when normalized by reference to beta-actin, was
      higher by a factor of 2 in postnatal (P1-6) UB and by a factor of 5 in CCD cells
      (P7-14) compared with the embryonic stage. Highly Na+-selective, low-conductance
      channels were identified in apical patches from both UB and CCD monolayers, but
      only CCD cells exhibited macroscopic, amiloride-sensitive Na+ currents in whole
      cell patch-clamp recordings. We conclude that alpha-ENaC mRNA and functional Na+
      channel protein are expressed already before morphogenesis of the CCD is
      completed and prior to the onset of epithelial NaCl reabsorption.

PMID- 9914409
TI  - Effect of the substituted benzaldehyde 12C79 on Cl--dependent K+ influx in human
      red blood cells.
AB  - Ouabain- and bumetanide-resistant K+ influx, and haemoglobin (Hb) O2 saturation,
      were measured in HbA red cells over a range of oxygen tensions (PO2 values) in
      the presence and absence of 12C79 (5 mM), a substituted benzaldehyde which
      increases the O2 affinity of Hb. PO2 values for half-maximal O2 saturation
      declined from 29+/-2 mmHg (mean +/-SEM, n=3) in control cells to 7+/-1 mmHg with
      12C79. In control cells, Cl--dependent K+ influx (indicative of KCl cotransport
      activity) was fully O2 dependent, i.e. inactive at low PO2 values. By contrast,
      in the presence of 12C79, KCl cotransport was largely resistant to inactivation
      at low PO2 values. Substantial cotransport activity was still present (>60% of
      that at high PO2 values) in N2, although O2 saturation was low (about 10%). In
      all cases, Cl--independent K+ influxes were low [<0.25 mmol (l cells h)-1] and
      unaffected by PO2 or 12C79. The significance of these results is discussed.

PMID- 9914411
TI  - The rat suspension model is also a good tool for inducing muscle hyperactivity.
AB  - The aim of the present study was to investigate changes in the mechanical
      characteristics of the rat epitrochlearis muscle as a result of a period of
      hyperactivity. A tail suspension model was used to impose postural activity in
      the forelimb musculature with the intention of inducing a relative slowness in
      the fast epitrochlearis muscle. A method of dual-controlled releases was used to
      obtain force-velocity and tension-extension relationships characterizing muscle
      mechanics. Results showed that: (1) mechanical characteristics are that of a fast
      twitch muscle and (2) suspension induces a decrease in the maximal shortening
      velocity and a decrease in the compliance of series elastic elements. Changes in
      fibre type proportions are consistent with these mechanical adaptations. This
      demonstrates that an usual model of muscle hypoactivity can also be used for
      imposing hyperactivity of a postural nature, inducing muscle transformations
      towards a slower twitch muscle.

PMID- 9914410
TI  - A novel, rapid and reversible method to measure Ca buffering and time-course of
      total sarcoplasmic reticulum Ca content in cardiac ventricular myocytes.
AB  - This paper outlines a simple method of estimating both the Ca-buffering
      properties of the cytoplasm and the time-course of changes of sarcoplasmic
      reticulum (s.r.) Ca concentration during systole. The experiments were performed
      on voltage-clamped ferret single ventricular myocytes loaded with the free acid
      of fluo-3 through a patch pipette. The application of caffeine (10 mM) resulted
      in a Na-Ca exchange current and a transient increase of the free intracellular Ca
      concentration ([Ca2+]i). The time-course of change of total Ca in the cell was
      obtained by integrating the current and this was compared with the measurements
      of [Ca2+]i to obtain a buffering curve. This could be fit with a maximum capacity
      for the intrinsic buffers of 114+/-18 micromol l-1 and Kd of 0.59+/-0.17 microM
      (n=8). During the systolic rise of [Ca2+]i, the measured changes of [Ca2+]i and
      the buffering curve were used to calculate the magnitude and time-course of the
      change of total cytoplasmic Ca and thence of both s.r. Ca content and Ca release
      flux. This method provides a simple and reversible mechanism to measure Ca
      buffering and the time-course of both total cytoplasmic and s.r. Ca.

PMID- 9914412
TI  - beta-adrenergic modulation of maxi-K channels in vascular smooth muscle via Gi
      through a membrane-delimited pathway.
AB  - Direct modulation of large-conductance Ca2+-activated K+ (maxi-K) channel by
      receptor-associated G protein in rabbit mesenteric arterial smooth muscle cells
      was studied using the outside-out patch clamp technique. Applying a beta
      adrenoceptor agonist (isoproterenol) increased maxi-K channel activity by 75%,
      and the effect was almost completely abolished by pretreating the cells with
      pertussis toxin but not with cholera toxin. When the antibody against Gi protein
      was present in the pipette solution the stimulatory effect of isoproterenol
      disappeared. These results suggest that beta-adrenoceptor stimulation increases
      maxi-K channel activity via a membrane-delimited pathway, probably through
      pertussis toxin-sensitive G protein (Gi).

PMID- 9914414
TI  - scalloped functions in a regulatory loop with vestigial and wingless to pattern
      the Drosophila wing.
AB  - The development of the Drosophila wing involves progressive patterning events. In
      the second larval instar, cells of the wing disc are allotted wing or notum fates
      by a wingless-mediated process and dorsal or ventral fates by the action of
      apterous and wingless. Notch-mediated signalling is required for the expression
      of the genes vestigial and scalloped in the presumptive wing blade. Later,
      wingless, Notch and cut are involved in cell fate specification along the wing
      margin. The function of scalloped in this process is not well understood and is
      the focus of this study. We show that patterning downstream of Notch and wingless
      pathways is altered in scalloped mutants. Reduction in scalloped expression
      results in a loss of expression of wing blade- and margin-specific markers.
      Misexpression of scalloped in the presumptive wing causes misexpression of
      scalloped, vestigial and wingless reporter genes. However, high levels of
      scalloped expression have a negative influence on wingless, vestigial and its own
      expression. Our results demonstrate that scalloped functions in a level-dependent
      manner in the presumptive wing blade in a loop that involves vestigial and
      itself. We suggest that wing development requires the regulated expression of
      scalloped together with vestigial-the "wing formation" effects of Vestigial in
      other imaginal discs are probably due to its interaction with the scalloped gene
      product normally expressed in these discs.

PMID- 9914413
TI  - Neural expression of hikaru genki protein during embryonic and larval development
      of Drosophila melanogaster.
AB  - Hikaru genki (HIG) is a putative secreted protein of Drosophila that belongs to
      immunoglobulin and complement-binding protein superfamilies. Previous studies
      reported that, during pupal and adult stages, HIG protein is synthesized in
      subsets of neurons and appears to be secreted to the synaptic clefts of neuron
      neuron synapses in the central nervous system (CNS). Here we report the analyses
      of distribution patterns of HIG protein at embryonic and larval stages. In
      embryos, HIG was mainly observed in subsets of neurons of the CNS that include
      pCC interneurons and RP5 motorneurons. At third instar larval stage, this protein
      was detected in a limited number of cells in the brain and ventral nerve cord.
      Among them are the motorneurons that extend their axons to make neuromuscular
      junctions on body wall muscle 8. Immunoelectron microscopy showed that these
      axonal processes as well as the neuromuscular terminals contain numerous vesicles
      with HIG staining, suggesting that HIG is in a pathway of secretion at this
      stage. Some neurosecretory cells were also found to express this protein. These
      data suggest that HIG functions in the nervous system through most developmental
      stages and may serve as a secreted signalling molecule to modulate the property
      of synapses or the physiology of the postsynaptic cells.

PMID- 9914415
TI  - Juvenile hormone modulates 20-hydroxyecdysone-inducible ecdysone receptor and
      ultraspiracle gene expression in the tobacco hornworm, Manduca sexta.
AB  - Insect molting and metamorphosis are orchestrated by ecdysteroids with juvenile
      hormone (JH) preventing the actions of ecdysteroids necessary for metamorphosis.
      During the molt and metamorphosis of the dorsal abdominal epidermis of the
      tobacco hornworm, Manduca sexta, the isoforms involved in the ecdysone receptor
      (EcR)/Ultraspiracle (USP) complex change with the most dramatic switch being the
      loss of USP-1 and the appearance of USP-2 during the larval and pupal molts. We
      show here that this switch in USP isoforms is mediated by high 20-hydroxyecdysone
      (20E) and that the presence of JH is necessary for the down-regulation of USP-1
      mRNA. The decrease of USP-1 mRNA in day 2 fourth instar larval epidermis in vitro
      required exposure to a high concentration (10(-5) M) of 20E equivalent to the
      peak ecdysteroid concentration in vivo, whereas the increase of USP-2 mRNA
      occurred at lower concentrations (effective concentrations, EC50=6.3x10(-7) M).
      During the pupal molt of allatectomized larvae which lack JH, USP-2 mRNA
      increased normally with the increasing ecdysteroid titer, whereas USP-1 mRNA
      remained high until pupation. When day 2 fifth instar larval epidermis was
      exposed to 500 ng/ml 20E in the absence of JH to cause pupal commitment of the
      cells by 24 h, USP-1 RNA remained at its high preculture level for 12 h, then
      increased two- to threefold by 24 h. The increase was prevented by the presence
      of 1 microgram/ml JH I which also prevents the pupal commitment of the cells. By
      contrast, USP-2 mRNA increased steadily with the same EC50 as in fourth stage
      epidermis, irrespective of the presence or absence of JH. Under the same
      conditions, mRNAs for both EcR-B1 and EcR-A isoforms were up-regulated by 20E,
      each in its own time-dependent manner, similar to that seen in vivo. These
      initial mRNA increases were unaffected by the presence of JH I, but those seen
      after 12 h exposure to 20E were prevented by JH, indicating a difference in
      response between larvally and pupally committed cells. The presence of JH which
      maintained larval commitment of the cells also prolonged the half-life of the EcR
      proteins in these cells. These results indicate that both EcR and USP RNAs are
      regulated by 20E and can be modulated by JH in a complex manner with only that of
      USP-2 apparently unaffected.

PMID- 9914416
TI  - Distinct structural domains in the planarian brain defined by the expression of
      evolutionarily conserved homeobox genes.
AB  - Homeobox genes such as orthodenticle in Drosophila and its mouse homologues, Otx1
      and Otx2, are known to be essential for rostral brain development. To investigate
      the molecular basis of brain evolution, we searched for otd/Otx-related homeobox
      genes in the planarian Dugesia japonica, and identified two genes, DjotxA and B,
      whose expression appears to be restricted to the cephalic ganglion (brain).
      DjotxA was expressed more medially, in the region containing the termini of the
      visual axons, and in the visual cells, suggesting involvement in establishment of
      the visual system. DjotxB was expressed in a discrete region just lateral to the
      DjotxA-positive domain, but not in the more lateral branch structures, which in
      turn are characterized by the expression of Djotp, a planarian homeobox gene
      related to mouse Orthopedia (Otp). In transverse sections of planarians, DjotxA
      and B expression were observed only at the anterior ends of the stumps,
      corresponding to the regional pattern of the regenerating brain. Our findings
      suggest that the planarian brain is composed of structurally distinct and
      functionally diverse domains which are defined by the discrete expression of the
      three evolutionarily conserved homeobox genes.

PMID- 9914417
TI  - The evolution of the hedgehog gene family in chordates: insights from amphioxus
      hedgehog.
AB  - The hedgehog family of intercellular signalling molecules have essential
      functions in patterning both Drosophila and vertebrate embryos. Drosophila has a
      single hedgehog gene, while vertebrates have evolved at least three types of
      hedgehog genes (the Sonic, Desert and Indian types) by duplication and divergence
      of a single ancestral gene. Vertebrate Sonic-type genes typically show conserved
      expression in the notochord and floor plate, while Desert- and Indian-type genes
      have different patterns of expression in vertebrates from different classes. To
      determine the ancestral role of hedgehog in vertebrates, I have characterised the
      hedgehog gene family in amphioxus. Amphioxus is the closest living relative of
      the vertebrates and develops a similar body plan, including a dorsal neural tube
      and notochord. A single amphioxus hedgehog gene, AmphiHh, was identified and is
      probably the only hedgehog family member in amphioxus, showing the duplication of
      hedgehog genes to be specific to the vertebrate lineage. AmphiHh expression was
      detected in the notochord and ventral neural tube, tissues that express Sonic
      type genes in vertebrates. This shows that amphioxus probably patterns its
      ventral neural tube using a molecular pathway conserved with vertebrates. AmphiHh
      was also expressed on the left side of the pharyngeal endoderm, reminiscent of
      the left-sided expression of Sonic hedgehog in chick embryos which forms part of
      a pathway controlling left/right asymmetric development. These data show that
      notochord, floor plate and possibly left/right asymmetric expression are
      ancestral sites of hedgehog expression in vertebrates and amphioxus. In
      vertebrates, all these features have been retained by Sonic-type genes. This may
      have freed Desert-type and Indian-type hedgehog genes from selective constraint,
      allowing them to diverge and take on new roles in different vertebrate taxa.

PMID- 9914418
TI  - Conservation of intracellular Wnt signaling components in dorsal-ventral axis
      formation in zebrafish.
AB  - The mechanism of early dorso-ventral axis specification in zebrafish embryos is
      not well understood. While beta-catenin has been clearly implicated as a
      determinant of the axis, the factors upstream and downstream of beta-catenin in
      this system are not defined. Unlike in Xenopus, where a sperm-induced cortical
      rotation is used to localize beta-catenin on the future dorsal side of the
      embryo, zebrafish do not have an obviously similar morphogenetic movement.
      Recently, a GSK-3 (Glycogen Synthase Kinase-3) binding protein (GBP) was
      identified as a novel member of the Wnt pathway required for maternal dorsal axis
      formation in Xenopus. GBP stabilizes beta-catenin levels by inhibiting GSK-3 and
      potentially provides a link between cortical rotation and beta-catenin
      regulation. Since zebrafish may use a different mechanism for regulating beta
      catenin, we asked whether zebrafish also express a maternal GBP. We report the
      isolation of the zebrafish GBP gene and show that it is maternally expressed and
      is present as mRNA ubiquitously throughout early embryonic development. Over
      expression of zebrafish GBP in frogs and fish leads to hyper-dorsalized
      phenotypes, similar to the effects resulting from over-expression of beta
      catenin, indicating that components upstream of beta-catenin are conserved
      between amphibians and teleosts. We also examined whether Tcf (T cell factor)
      functions in zebrafish embryos. As in frogs, ectopic expression of a dominant
      negative form of XTcf-3 ventralizes zebrafish embryos. In addition, ectopic beta
      catenin expression activates the promoter of the Tcf-dependent gene siamois,
      indicating that the step immediately downstream of beta-catenin is also conserved
      between fish and frogs.

PMID- 9914420
TI  - Green fluorescent proteins with short half-lives as reporters in Dictyostelium
      discoideum.
AB  - We describe two modifications of the popular reporter green fluorescent protein
      (GFP) which have short half-lives in our system, the cellular slime mould
      Dictyostelium discoideum. One of these bears an N-terminal ubiquitin; this GFP
      was originally planned to be a substrate of the "N-end-rule" pathway, but
      deubiquitination does not seem to occur, and a degradation by the UFD (ubiquitin
      fusion-degradation pathway seems more probable. The protein half-life is about 3
      5 h. The second construct has an N-terminus derived from the L11 ribosomal
      protein; it is transported to the nucleus and broken down much more rapidly than
      the ubiquitin fusion (protein half-life about 30 min). We show examples of the
      use of these reporters in the study of gene expression in Dictyostelium.

PMID- 9914419
TI  - A Caenorhabditis elegans homeobox gene expressed in the male tail, a link between
      pattern formation and sexual dimorphism?
AB  - ceh-7 is a small Caenorhabditis elegans homeobox gene. We have shown that this
      gene is transcribed. Examination of the expression pattern of ceh-7 using
      reporter constructs revealed that it is expressed in a few cells of the male
      tail, which form a ring around the rectum. The most posterior member of the C.
      elegans Hox cluster, egl-5, an Abd-B homologue, has previously been shown to be
      required for the proper development of several blast cells in the male tail. We
      have examined the expression of ceh-7 in mutant backgrounds of egl-5 and also mab
      5, an Antp/Ubx/Abd-A homologue. We find that ceh-7 is not expressed in egl-5
      mutants, but is still expressed in mab-5 mutants.

PMID- 9914421
TI  - Quo vadis? The future of basic research in orthopedics in Japan.

PMID- 9914422
TI  - Knee injury and obesity in patients undergoing total knee replacement: a
      retrospective study in 115 patients.
AB  - The prevalence of obesity and previous knee injury was assessed in a
      retrospective study of 115 patients under-going total knee replacement due to
      osteoarthritis. Obesity was considered a contributing factor in the development
      of osteoarthritis in 37% of the patients, and 33% of the patients had had an
      injury to the knee in question. Unilateral osteoarthritis was significantly more
      frequent than bilateral osteoarthritis among patients with a history of previous
      knee injury. The association of previous injury to the knee and unilateral
      osteoarthritis was stronger in men than women. Aggressive treatment of patients
      with knee injuries seems warranted.

PMID- 9914423
TI  - Treatment of intraarticular fractures with modified herbert screws (analysis of
      69 cases).
AB  - Sixty-nine patients with intraarticular fractures were treated with modified
      Herbert screws between August 1988 and December 1994. They were followed for an
      average of 20 months (range, 6 months to 4 years). The final results were
      assessed in terms of patient satisfaction, clinical examination, and radiographic
      findings. The success rate was 89.8% (62/69). There were no serious
      complications. The authors believe the advantages of the modified Herbert screw
      over the Arbeitsgemeinschaft fur osteosynthesefrogen cancellous bone screw are
      many. The modified Herbert screw provides rigid internal fixation with strong
      purchase on the bone, so that additional immobilization in plaster is seldom
      required. It can be inserted through articular cartilage and appropriately buried
      beneath the articular surface. It is not necessary to remove the screw after bone
      union. This type of fixation can be widely used in the clinical setting.

PMID- 9914424
TI  - Gait analysis before and after unilateral total knee arthroplasty. Study using a
      linear regression model of normal controls -- women without arthropathy.
AB  - Stepwise multiple regression analysis (forward method) was performed with 22 gait
      variables obtained from the free and slow gait of 35 normal controls (women
      without knee arthropathy). These 22 variables were target variables, and
      velocity, age, body height, and body weight were explanatory variables. Velocity
      showed the greatest effect on the gait variables, followed by weight, age, and
      height. Of the 22 target variables, 16 could be explained by a significant level
      of difference of P < 0.01. A linear regression model of normal gait was then
      established, based on the judgment that these 16 gait variables were greatly
      affected by four variables -- velocity, age, height, and weight. Since this model
      does not perfectly represent the observed values, we compared the observed
      value/predicted value ratios in different groups to compensate for their
      differences. The free gait velocity in 20 osteoarthritic patients, 1 year or more
      after unilateral total knee arthroplasty (TKA), and who had no pain in the
      contralateral knee was lower than in the normal controls. In comparisons using
      linear regression models, step length was shorter, step width was longer, and
      gait cycle was shorter than in controls. Single support time was shorter and
      double support time was longer. Of the ground reaction forces, the first peak of
      the vertical component and the peak of the driving force of the fore-aft
      component were smaller than in controls. The total range of motion (TRM) in the
      stance phase was less than in controls. These results show quantitatively not
      only that the velocity of gait after TKA is lower than in normal controls, but
      also that gait patterns are different. In eight osteoarthritic patients assessed
      before and after TKA, and who had no pain in the contralateral knee, free gait
      velocity increased 6 months post-operation, but showed no further changes at 1
      year. A linear regression study comparing the gait before TKA and 6 months post
      TKA revealed that step time, single support time, double support time, and step
      width, and -- with regard to ground reaction forces -- the peaks of the driving
      force and the braking force of the fore-aft component, and TRM in the stance
      phase all approached the levels in the normal controls. No further changes were
      observed 1 year postoperatively. Although our models were not perfect, we were
      able to clarify the differences in gait variables between a TKA group and normal
      controls and the improvements from pre- to post TKA by normalizing the influence
      of the four independent variables, (velocity, age, weight, and height) with
      particular emphasis on gait velocity.

PMID- 9914425
TI  - Expression of gp145trkB in the early stage of Schwann cell tube formation.
AB  - We investigated the expression of tyrosine kinase receptors (trkBs) and their
      ligand, brain-derived neurotrophic factor (BDNF), in isolated sciatic nerve
      segments of rat in a silicone chamber model devoid of axonal contact, using an
      immunohistochemical technique. The receptor gp 95trkB was not detected during the
      first 3 weeks but was strongly expressed in the nerve stumps on day 21. In
      contrast, gp 145trkB immunoreactivity was readily detected in the Schwann cells
      in the nerve stumps between days 1 and 7 after isolation. Immunohistochemical
      analysis using anti-S-100 antibody demonstrated that Schwann cell tube formation
      within the silicone chamber had been completed by the third week, which suggested
      that gp 95trkB began to be produced by Schwann cells after completion of Schwann
      cell tube formation. Considering the low level of BDNF production during the
      first week, molecules other than BDNF may be ligands for gp 145trkB in the
      silicone chamber model devoid of axonal contact.

PMID- 9914426
TI  - Capillary changes with fenestrations in the contralateral soleus muscle of the
      rat following unilateral limb immobilization.
AB  - Using electron microscopy, we examined structural changes in the capillaries of
      the immobilized and contralateral soleus muscles in the rat after the unilateral
      limb had been immobilized for 4 weeks. Individual contralateral muscle fibers
      showed a normal structure, compared with the structure in the immobilized muscle
      fibers. Most capillaries in the contralateral muscle were of the continuous type.
      However, about 5% of the examined capillaries in these muscles in each rat had
      fenestrations. The non-nuclear portions of the endothelial cells in these
      capillaries were extremely thin and were perforated by several fenestrations that
      were bridged by a single-layered diaphragm. The fenestration of capillaries in
      the contralateral muscle may have been caused by some the unilateral limb
      immobilization.

PMID- 9914427
TI  - Exposure of macrophage-like cells to titanium particles does not affect bone
      resorption, but inhibits bone formation.
AB  - We examined the capacity of culture supernatants of macrophage-like cells exposed
      to titanium particles to influence bone formation and bone resorption, our aim
      being to elucidate the mechanism of implant loosening. A mouse macrophage-like
      cell line, J774, was exposed to titanium particles and the concentrations of
      prostaglandin E2, tumor necrosis factor-alpha, interleukin-1alpha, and
      interleukin-6 in the supernatants were measured. Titanium particles stimulated
      the J774 cells to release tumor necrosis factor-alpha, whereas prostaglandin E2,
      interleukin-1alpha and interleukin-6 concentrations remained low. The bone
      resorptive activity of the supernatants was measured by determining 45Ca release
      from cultured pre-labeled newborn mouse calvariae. The culture supernatants of
      J774 cells exposed to titanium particles showed no significant difference in bone
      resorptive activity in mouse calvariae from that of culture supernatants of J774
      cells not exposed to titanium particles. The bone-forming activity of the
      supernatant was evaluated by determining bone nodule formation and alkaline
      phosphatase activity in cultured mouse calvaria cells. The bone-forming activity
      of the supernatants exposed to titanium particles was significantly decreased
      compared with the supernatants of unexposed J774 cells. This inhibition was
      reversed by the addition of anti-tumor necrosis factor-alpha neutralizing
      antibody. We conclude that tumor necrosis factor-alpha released from J774 cells
      exposed to titanium particles played an important role in the inhibition of bone
      formation rather than in the stimulation of bone resorption.

PMID- 9914428
TI  - Asymptomatic brain abscess as a complication of halo orthosis: report of a case
      and review of the literature.
AB  - The halo external orthosis has been used extensively for cervical immobilization
      after spine surgery or trauma, usually without serious complications. However,
      nine brain abscesses have been reported as complications following the use of
      halo orthosis. We report on a 53-year-old man who underwent anterior cervical
      fusion for cervical myelopathy, followed by the application of a halo orthosis.
      Approximately 4 weeks postfusion, loosening of the right anterior pin was
      recognized and the pin was tightened, as the pin-site was clean. One week later,
      purulent material was discharged from the pin hole when the pin was removed after
      it had loosened again. Enhanced computed tomography (CT) demonstrated an abscess
      on the right side of the brain. After the administration of antibiotics, the
      abscess resolved without surgical intervention. We describe asymptomatic brain
      abscess complicating the use of a halo orthosis and review the clinical features,
      symptoms, and outcomes; we also discuss the mechanism that induced brain abscess.
      Most reported cases of abscess have been associated with pin-site infection or
      tightening after late pin loosening. The present case indicates the importance of
      early recognition of symptoms and signs associated with brain abscess in patients
      with a halo orthosis.

PMID- 9914429
TI  - Total shoulder arthroplasty -- current problems and possible solutions.
AB  - The concept and design of a cemented unconstrained total shoulder arthroplasty
      (TSA), introduced by Charles Neer II 25 years ago, has been successful in the
      management of degenerative and inflammatory conditions of the shoulder,
      controlling pain and, in many patients, significantly improving function. The
      clinical outcome is very much determined by the nature and severity of the
      pathology, as well as by the surgeon's experience and ability to correctly locate
      and fix the components. Total shoulder arthroplasty is a technically difficult
      procedure with perhaps a greater potential for technical errors and complications
      compared with other commonly performed arthroplasties. Current systems are
      modular on the humeral side, with varying head diameters and neck lengths,
      allowing more accurate coverage of the cut surface of the humeral neck and
      improved ability to establish the position of the joint line within the
      requirements of correct soft tissue tension and balance. Cemented all
      polyethylene glenoid components remain the most favored, but the majority now
      have an increased radius of curvature compared with their corresponding humeral
      head, to allow translation during movement. Aseptic glenoid component loosening
      is the most frequently encountered long-term complication and is hastened by
      conforming prostheses, incorrect positioning, rotator cuff tears, and capsular
      contractures, but is protected by secure glenoid fixation. Cemented one-piece
      metal-backed glenoids have been disappointing, but non-cemented glenoids are
      being trialed with promising early results, although they have introduced their
      own particular problems of rapid polyethylene wear and component dissociation.
      Although cemented humeral components have a very low incidence of symptomatic
      loosening, most surgeons currently use press-fit designs supplemented with
      metaphyseal porous coating for osseous integration. Based on increased
      understanding of the morphology of the upper humerus, current designs are
      evolving with increased modularity, allowing the surgeon to choose the
      appropriate size, inclination, offset and version of the humeral component. These
      changes will, it is hoped, result in improved functional recovery and increased
      survivorship of the glenoid component.

PMID- 9914430
TI  - Diagnosis and treatment of soft tissue tumors.
AB  - In the management of soft-tissue tumors, accurate diagnosis, using a combination
      of clinical, radiographic, and histological data, is critical in optimizing
      outcome. Radiographic diagnoses can be useful, but they cannot accurately predict
      histology or whether a lesion is benign or malignant. Therefore, all soft lumps
      that persist or grow should be biopsied if possible. Fine-needle aspiration
      biopsy is useful in differentiating benign from malignant lesions. Core-needle
      biopsies can yield a histological diagnosis when the sample is sufficiently
      large. When open biopsy is required, the skin incision must be carefully placed
      so that the biopsy site can be completely excised if the lesion is subsequently
      found to be malignant. Excisional biopsy should be used only for small lesions or
      when the surgeon is confident that the lesion is benign. If, following excision,
      the lesion is found to be malignant or desmoid, additional surgery with an
      adequate excision margin should be performed. In the resection of high-grade
      sarcomas treated by surgery alone or resistant to preoperative adjuvant
      therapies, a "curative (wide) margin" must be achieved. We occasionally use
      preoperative radiation with or without hyperthermia for malignant lesions in the
      vicinity of neurovascular structures where adequate surgical margins are unlikely
      to be achieved. The use of chemotherapy is justified only in small-cell sarcomas
      in which metastasis occurs frequently and chemotherapy is known to be effective.
      For high-grade spindle-cell or pleomorphic sarcomas, the value of adjuvant
      chemotherapy remains controversial and needs investigation.

PMID- 9914431
TI  - Diagnosis, treatment, and complications of thoracic outlet syndrome.
AB  - New concepts regarding the diagnosis and treatment of thoracic outlet syndrome,
      double crush syndrome related to thoracic outlet syndrome, and minor traumatic
      dystrophy related to thoracic outlet syndrome are explained.

PMID- 9914432
TI  - Selective immunotoxin-induced cholinergic deafferentation alters blood flow
      distribution in the cerebral cortex.
AB  - Adult rats received intracerebroventricular (i.c.v.) administration of either
      phosphate buffer (PBS) or 192 IgG-saporin (Toxin), 3.6 micrograms rat-1, a
      cholinergic immunotoxin. Six to eight weeks later, the animals received a
      continuous intravenous (i.v.) infusion of either physostigmine (4.2 micrograms kg
      1 min-1) or saline, followed by measurement of cerebral cortical blood flow (CBF)
      with the autoradiographic Iodo-14C-antipyrine methodology in four groups of
      animals: Toxin i.c.v.+saline i.v. (n=9), Toxin i.c.v.+physostigmine i.v. (n=6),
      PBS i.c.v.+saline i.v. (n=6) and PBS i.c.v. +physostigmine i.v. (n=6). Choline
      acetyltransferase activity (ChAT) was assessed with Fonnum's method in samples of
      cortical tissue adjacent to the sites of CBF measurement. ChAT decreased in all
      regions of the Toxin groups when compared to PBS (% decrease: hippocampus=93%,
      neocortex=80-84%, entorhinal-piriform cortex=42%, amygdala=28%). CBF decreased
      globally in Toxin+SAL, most severely in posterior parietal and temporal regions
      (24-40% decrease from PBS+saline). Physostigmine enhanced CBF predominantly in
      these same areas both in PBS and Toxin animals although to a lesser extent in the
      latter. Our results demonstrate the importance of cholinergic mechanisms in the
      control of CBF. The similarity between the topography of CBF decrease following
      administration of the immunotoxin to that observed in Alzheimer's disease
      suggests that the CBF pattern observed in this disease may be the result of
      cholinergic deafferentation.

PMID- 9914433
TI  - Presynaptic excitability changes of group Ia fibres to muscle nociceptive
      stimulation in humans.
AB  - Tonic muscle nociceptive discharge evoked chemically from the foot extensor
      digitorum brevis muscle in man produces a depression of Ia excitation and Ib
      inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both
      these changes partly result from presynaptic inhibition of Ia fibres projecting
      to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is
      tested. Convergence of Ia fibres on these interneurones was deduced from evidence
      that reducing the excitatory effect of the extensor Ia fibres (by potentiation of
      their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced
      potentiation of Ia presynaptic inhibition was deduced from the following
      congruent results obtained by two independent methods: (1) depression of
      heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns;
      (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical
      activation of the tibialis anterior primary spindle afferents. It is concluded
      that nociceptive volleys arising from dorsal foot muscles facilitate the activity
      of interneurones intercalated in pathways responsible for presynaptic inhibition
      of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition
      depresses the excitability of interneurones mediating group I non-reciprocal
      inhibition, thus resulting in Ib disinhibition of Sol Mns.

PMID- 9914434
TI  - Apoptosis and expression of p53 response proteins and cyclin D1 after cortical
      impact in rat brain.
AB  - We measured the temporal profile and cellular identification of apoptosis in rat
      brain after cortical contusion injury. Double staining immunohistochemistry was
      also used to investigate the relationship between apoptotic cell death and
      selective protein expression associated with DNA damage and repair (p53, Bax,
      MDM2, WAF1, Gadd45, PCNA) and cell cycle protein, Cyclin D1, in male Wistar rats
      48 h after injury. Cortical contusion was induced in male Wistar rats with a
      pneumatic impactor device. The animals were sacrificed at different times after
      trauma (1, 2, and 14 h and 1, 2, 4, 7 and 14 days; n=4 per time point). Sham
      operated rats (n=4) and normal rats not subjected to any surgical procedure (n=4)
      were used as controls for temporal profile determination. Additional 11 rats were
      used for study of protein expression. Coronal brain sections were analyzed using
      an in situ terminal deoxynucleotdyl transferase-mediated biotinylated
      deoxyuridine triphosphate nick end labeling (TUNEL), hematoxylin, and
      immunohistochemical double staining methods. Apoptotic cells were observed as
      early as 2 h after the impact. Apoptotic cell death peaked at 2 days, gradually
      tapering off afterward, although scattered apoptotic cells were detected at 2
      weeks after the impact. The number of apoptotic cells at 2 days far exceeded
      their number at other times (p=0.009). Apoptotic cells were observed primarily in
      the cortex adjacent to the site of injury. In addition, apoptotic cells in
      conjunction with few injured cells were present in the ipsilateral hippocampus
      and localized to the granule layer of dentate gyrus. Our data indicate that DNA
      fragmentation is present in nearly all neurons subacutely after cortical
      contusion and persists for at least 2 weeks thereafter. Apoptosis is also present
      in neurons localized to the hilus of the dentate gyrus at a site remote from the
      area of injury suggesting a selective role for apoptosis in promoting secondary
      brain damage and dysfunction after traumatic brain injury. Using double staining,
      we were able to show that a great majority of apoptotic cells (>95%) were neurons
      and the rest were astrocytes and endothelial cells. Proteins associated with DNA
      damage and repair (p53, Bax, MDM2, WAF1, Gadd 45, PCNA) were expressed in the
      cytoplasm of normal cells of naive and sham rats. These proteins were
      translocated to the nuclei of apoptotic and injured cells at 48 h after cortical
      contusion. Cyclin D1 was not present in apoptotic cells. The differential
      expression of proteins associated with DNA damage, repair and the cell cycle
      protein Cyclin D1 in the contused brain suggest a potential role for these
      proteins in cell survival and apoptosis after cortical contusion.

PMID- 9914435
TI  - The glutamate induced phase shift in the SCN slice: a two pulse study.
AB  - The short-term dynamics of resetting the circadian 'clock' was assessed by a
      double-pulse paradigm in vitro. On day 1, single and double 1 h 'pulses' of 1 mM
      l-glutamate were applied to the rat suprachiamastic nuclei (SCN). On days 2 and
      3, single unit activity (SUA) was recorded and time-of-peak SUA was used as a
      phase marker of the circadian rhythm. The time-of-peak in untreated slices at
      'Zeitgeber' time (ZT; hours after lights-on) 6, was used to evaluate effects of
      glutamate on phase. In accordance with published data, a single glutamate pulse
      at ZT 14 resulted in a 3 h delay of peak SUA on days 2 and 3. A 2nd pulse, given
      3 h after a 1st pulse, resulted in two distinct peaks on day 2: a 1st at ZT 7 and
      a 2nd at ZT 12, i. e., a 6 h phase delay and hence twice the delay obtained after
      a single pulse. On day 3, no peak in SUA was observed which indicates that a new
      steady state was not reached on day 2. The bimodal distribution of SUA on day 2
      corroborates other findings which suggest that the SCN comprises two distinct
      neuronal populations with circadian firing patterns that are normally coupled
      but, possibly due to different sensitivities to glutamate, can desynchronize. The
      additive phase-shifting effect of two consecutive glutamate pulses suggests that,
      at least for one sub-population of SCN neurons, the phase shift is completed
      within 3 h.

PMID- 9914436
TI  - Cerebellar atrophy in Alzheimer's disease-clinicopathological correlations.
AB  - Morphometry of the cerebellum of 11 subjects who died in the severe, final stage
      of Alzheimer's disease (AD) and of five age-matched subjects without dementia
      revealed significant atrophy in the AD group, with a decrease in the volume of
      the molecular layer by 24% and of the granular layer by 22% in comparison with
      controls. The 32% decrease in the total number of Purkinje cells that was
      observed correlates with the atrophy of the molecular layer, whereas the 30%
      reduction in the total number of granule cells correlates with the atrophy of the
      molecular and granular layers. A unique pattern of Alzheimer-type pathology was
      observed in the cerebellum: (1) there were no neurofibrillary changes in the
      cerebellum of either the control or the AD subjects, (2) there was almost the
      same extent of leptomeningeal and cortical amyloid angiopathy in the normal aged
      subjects and in the AD patients, and (3) the presence of plaques was noted in the
      AD group, but not in the control group. This pattern of pathology suggests that
      two factors might be considered in the etiopathogenesis of cerebellar atrophy:
      (1) transneuronal degeneration and neuronal loss resulting from primary
      pathologic changes in cerebral structures and (2) parenchymal cerebellar ss
      amyloidosis. The correlation between the temporal duration of AD and both the
      decrease of the total number of granule cells (r=0.86, p<0.01) and the volumetric
      loss of the molecular (r=0.73, p<0.05) and granular (r=0.93, p<0.001) layers of
      the cerebellar cortex indicates that these cerebellar atrophic changes are likely
      to be related to the basic pathologic process of AD. Similarly, the correlation
      between the most complex parameter the atrophy of the cerebellar cortex and the
      Functional Assessment Staging (FAST) measure of the clinical severity of AD at
      the time of demise (r=0.63, p<0.05) as well as with the duration of AD (r=0.78,
      p<0.01) indicates that cerebellar pathology, when viewed holistically, evolves
      continuously in association with clinical changes throughout the clinically
      manifest course of AD.

PMID- 9914437
TI  - The short-acting anesthetic propofol produces biphasic effects-depression and
      withdrawal rebound overshoot-on some (but not all) limbic evoked potentials in
      the behaving rat.
AB  - Propofol, the relatively new, short-acting general anesthetic, markedly enhances
      the action of GABA at the GABAA receptor. To evaluate its effects on field
      potentials evoked in the dentate gyrus (DG) during the anesthetic and recovery
      periods, propofol was administered intraperitoneally to behaving rats bearing
      stimulating electrodes in the dorsal perforant path (DPP), where medial perforant
      path fibers predominate, and in the anterior piriform cortex (PC; i.e., olfactory
      cortex), and recording electrodes in the DG. Input from the PC reaches the DG via
      the lateral perforant path. Population slow waves (SWs) were evoked by paired
      pulse stimulation of the PC at a 32 ms interstimulus interval (ISI) to produce
      paired-pulse facilitation in the awake animal. We had previously demonstrated
      that amplitude of SW2 (produced by the second stimulus) was greatly decreased by
      GABAergic drugs and increased by antiGABAergic convulsant agents. After
      administration of propofol, mean amplitude of SW2 decreased immediately and
      remained low for 30-60 min during propofol-induced sleep (as expected), then
      unexpectedly increased to about 1.5- to 2-fold above pretreatment levels at 2-4 h
      before gradually returning to pretreatment levels. In addition, the DPP was
      stimulated to produce either paired-pulse inhibition (20 ms ISI) or facilitation
      (32 ms ISI) of DG population spikes (PSs) in the awake animal. PS2 was much more
      inhibited during propofol-induced sleep, than during the pretreatment period,
      consistent with an expected marked increase in recurrent inhibition. An overshoot
      in PS2 amplitude was observed only occasionally during recovery, suggesting that
      withdrawal overshoot in amplitudes is more characteristic of PC-evoked DG SW2
      potentials. The overshoot in SW2 amplitude during recovery may have been related
      to propofol's 'rapid on-rapid off' actions on the GABAA receptor, perhaps
      resulting in a phenomenon like the 'GABA withdrawal syndrome'. Such an effect, if
      true, may help explain the rare occurrence of seizures, especially during
      recovery, associated with its use clinically.

PMID- 9914439
TI  - Age-dependent alteration of metabolic response to photic stimulation in the human
      brain measured by 31P MR-spectroscopy.
AB  - Effects of photic stimulation (PS) on energy metabolism were examined in the
      occipital cortex of 25 healthy volunteers aged 23-69 years old using phosphorus
      31 magnetic resonance spectroscopy (31P-MRS). A significant effect of photic
      stimulation was found only for intracellular pH (p<0.05 by repeated measures
      analysis of variance) but not for any peak area ratios. An interaction between
      intracellular pH and age were statistically significant (p<0.005), and the
      interaction between phosphocreatine and age was close to significance (p=0.06).
      In subjects aged more than 40 years old, phosphocreatine was significantly
      decreased during the photic stimulation (p<0.05, multiple comparison by Dunnett's
      method), and intracellular pH tended to be elevated just after the stimulation
      (p=0.07). There were no significant changes in these values in younger subjects.
      These results suggest that no significant effect of photic stimulation on brain
      energy metabolism was found in younger subjects, and that significant effects of
      photic stimulation on intracellular pH and phosphocreatine were found in middle
      aged subjects. Metabolic response of the human brain to photic stimulation may be
      dependent on age.

PMID- 9914438
TI  - An improved low-permeability in vitro-model of the blood-brain barrier: transport
      studies on retinoids, sucrose, haloperidol, caffeine and mannitol.
AB  - Primary cultures of porcine brain capillary endothelial cells grown on collagen
      coated polycarbonate membranes were used to build up an in vitro-model for the
      blood-brain barrier. Improved cultivation techniques allowed cell-storage and
      experiments under serum-free conditions. We employed this model to perform
      permeability studies in vitro with the radioactively labelled marker substances
      sucrose, retinoic acid, retinol, haloperidol, caffeine, and mannitol.
      Permeability values obtained with this blood-brain barrier model (1. 0x10-6 cm/s
      for sucrose, 6.2x10-6 cm/s for retinoic acid, 4.8x10-6 cm/s for retinol, 49.5x10
      6 cm/s for haloperidol, 62.4x10-6 cm/s for caffeine, and 1.8x10-6 cm/s for
      mannitol) show a good correlation to data which are already known from in vivo
      experiments. As judged by the sucrose permeability our blood-brain barrier model
      is less permeable than numerous other models published so far. Therefore it
      represents a powerful tool for in vitro-prediction of blood-brain barrier
      permeability of drugs and offers the possibility to scan a large quantity of
      drugs for their potential to enter the brain.

PMID- 9914440
TI  - Activation of neuroblast proliferation in explant culture of the Drosophila
      larval CNS.
AB  - The developmental control of neuroblast proliferation is absolutely required for
      the assembly and function of the central nervous system. A lethal mutation in
      trol results in the failure of quiescent neuroblasts to begin division at the
      appropriate time. I have established a culture system in which quiescent
      neuroblasts in explants of Drosophila larval CNSs initiate cell division in vitro
      to normal in vivo levels. This activation requires removal of the CNS for culture
      after a specific developmental stage and the presence of fetal calf serum or a
      larval extract in the medium. Either supplement is effective when heat-treated.
      Substitution of the steroid hormone ecdysone or the non-steroidal ecdysone analog
      RH5992 for either fetal calf serum or larval extract also results in activation
      of neuroblast proliferation. Culture of trolsd CNSs with wildtype larval extract
      or ecdysone results in the defective neuroblast proliferation phenotype observed
      in trol mutants in vivo, while culture of wildtype CNSs with trolsd extract
      produces normal neuroblast proliferation.

PMID- 9914441
TI  - Selective neurodegeneration induced in rotation-mediated aggregate cell cultures
      by a transient switch to stationary culture conditions: a potential model to
      study ischemia-related pathogenic mechanisms.
AB  - Aggregating brain cell cultures at an advanced maturational stage (20-21 days in
      vitro) were subjected for 1-3 h to anaerobic (hypoxic) and/or stationary
      (ischemic) conditions. After restoration of the normal culture conditions, cell
      loss was estimated by measuring the release of lactate dehydrogenase as well as
      the irreversible decrease of cell type-specific enzyme activities, total protein
      and DNA content. Ischemia for 2 h induced significant neuronal cell death.
      Hypoxia combined with ischemia affected both neuronal and glial cells to
      different degrees (GABAergic neurons>cholinergic neurons>astrocytes). Hypoxic and
      ischemic conditions greatly stimulated the uptake of 2-deoxy-D-glucose,
      indicating increased glucose consumption. Furthermore, glucose restriction (5.5
      mM instead of 25 mM) dramatically increased the susceptibility of neuronal and
      glial cells to hypoxic and ischemic conditions. Glucose media concentrations
      below 2 mM caused selective neuronal cell death in otherwise normal culture
      conditions. GABAergic neurons showed a particularly high sensitivity to glucose
      restriction, hypoxia, and ischemia. The pattern of ischemia-induced changes in
      vitro showed many similarities to in vivo findings, suggesting that aggregating
      brain cell cultures provide a useful in vitro model to study pathogenic
      mechanisms related to brain ischemia.

PMID- 9914442
TI  - Differential responses by neurotensin systems in extrapyramidal and limbic
      structures to ibogaine and cocaine.
AB  - Ibogaine (Endabuse) is a psychoactive indole alkaloid found in the West African
      shrub, Tabernanthe iboga. This drug interrupts cocaine and amphetamine abuse and
      has been proposed for treatment of addiction to these stimulants. However, the
      mechanism of action that explains its pharmacological properties is unclear.
      Since previous studies demonstrated differential effects of psychotomimetic drugs
      (cocaine and methamphetamine) on neuropeptides such as neurotensin (NT), the
      present study was designed to determine: (1) the effects of ibogaine on striatal,
      nigral, cortical, and accumbens neurotensin-like immunoreactivity (NTLI); (2) the
      effects of selective dopamine antagonists on ibogaine-induced changes in NT
      concentrations in these brain areas; and (3) the effects of ibogaine pretreatment
      on cocaine-induced changes in striatal, nigral, cortical and accumbens NTLI
      content. Ibogaine treatments profoundly affected NT systems by increasing
      striatal, nigral, and accumbens NTLI content 12 h after the last drug
      administration. In contrast, NTLI concentrations were not significantly increased
      in the frontal cortex after ibogaine treatment. The ibogaine-induced increases in
      NTLI in striatum, nucleus accumbens and substantia nigra were blocked by
      coadministration of the selective D1 receptor antagonist, SCH 23390. The D2
      receptor antagonist, eticlopride, blocked the ibogaine-induced increase in nigral
      NTLI, but not in striatum and nucleus accumbens. Ibogaine pretreatment
      significantly blocked the striatal and nigral increases of NTLI resulting from a
      single cocaine administration. Whereas many of the responses by NT systems to
      ibogaine resembled those which occur after cocaine, there were also some
      important differences. These data suggest that NT may contribute to an
      interaction between ibogaine and the DA system and may participate in the
      pharmacological actions of this drug.

PMID- 9914443
TI  - Intravascular infusions of soluble beta-amyloid compromise the blood-brain
      barrier, activate CNS glial cells and induce peripheral hemorrhage.
AB  - Vascular wall levels of soluble beta-amyloid1-40 (Abeta1-40) are elevated in
      Alzheimer's disease (AD). Moreover, plasma Abeta levels are increased in familial
      AD, as well as in some cases of sporadic AD. To determine the histopathologic and
      behavioral consequences of elevated vascular Abeta levels, Abeta1-40 (50
      micrograms in distilled water) or vehicle was intravenously infused twice daily
      into 3-month old male Sprague-Dawley rats for 2 weeks. Intravenous Abeta
      infusions impaired blood-brain barrier integrity, as indicated by substantial
      perivascular and parenchyma IgG immunostaining within the brain. Also evident in
      Abeta-infused animals was an increase in GFAP immunostaining around cerebral
      blood vessels, and an enhancement of OX-42 microglial immunostaining in brain
      white matter. Gross pulmonary hemorrhage was noted in most Abeta-infused animals.
      All the observed changes occurred in the absence of Congo red birefringence. No
      significant cognitive deficits were present in Abeta-infused animals during water
      maze acquisition and retention testing, which was conducted during the second
      week of treatment. These results indicate that circulating Abeta can: (1) induce
      vessel dysfunction/damage in both the brain and the periphery without complex
      Abeta fibril formation/deposition, and (2) induce an activation of brain
      astrocytes and microglia. Taken together, our results suggest that if circulating
      Abeta is elevated in AD, it is likely to have a pathophysiologic role.

PMID- 9914444
TI  - Effects of hypoxia induced by Na2S2O4 on intracellular calcium and resting
      potential of mouse glomus cells.
AB  - Isolated and cultured glomus cells, obtained from mouse carotid bodies, were
      superfused with Ham's F-12 equilibrated with air (mean PO2, 119 Torr; altitude
      1350 m). [Ca2+]o was 3.0 mM. In one experimental series, dual cell penetrations
      with microelectrodes measured intracellular calcium ([Ca2+]i) and the resting
      potential (Em). In another series, [Ca2+]i was measured with Indo-1/AM, dissolved
      in DMSO. Normoxic cells had a mean Em of -42.4 mV and [Ca2+]i was about 80 nM
      (measured with both methods). The calculated calcium equilibrium potential (ECa)
      was 137+/-0.74 mV. Hypoxia, induced by Na2S2O4 1 mM, reduced pO2 to 10-14 Torr.
      This effect was accompanied by cell depolarization to -19.1 mV. Hypoxia increased
      [Ca2+]i to 231 nM when detected with Ca-sensitive microelectrodes, but only to
      130.2 nM when measured with Indo-1/AM. Calcium increases were preceded by
      decreases in [Ca2+]i, which also were more pronounced with microelectrode
      measurements. CoCl2 1 mM blocked the hypoxic [Ca2+]i increase and exaggerated the
      decreases in [Ca2+]i. Correlations between DeltaEm and Delta[Ca2+]i during
      hypoxia were significant (p<0.05) in 19% of the cells. But, in 29% of them
      significance was at the p<0.1 level. In the rest (52%), there was no correlation
      between these parameters. Thus, voltage-gated calcium channels are rare in mouse
      glomus cells. Their activation by depolarization cannot explain the two to
      threefold increase in [Ca2+]i seen during hypoxia. More likely, [Ca2+]i increase
      may be due to hypoxic inactivation of a Ca-Mg ATPase transport system across the
      cell membrane. The blunting of hypoxic [Ca2+]i increase, seen in Indo-1/AM
      experiments, is probably due to its solvent (DMSO), which also depresses hypoxic
      cell depolarization.

PMID- 9914445
TI  - Effects of tetanus toxin on functional inhibition after injection in separate
      cortical areas in rat.
AB  - Tetanus Toxin is widely used as a model of chronic focal epilepsy and is assumed
      to act by blocking neurotransmitter release with high selectivity for inhibitory
      synapses. However, the exact mechanisms are not fully understood, since, e.g.,
      GABA release is only temporarily decreased although epileptiform activity
      persists pointing towards a change in the interplay of excitation and inhibition.
      Furthermore there have been reports about different effects of tetanus toxin
      after injection in separate brain areas. Therefore, we investigated the
      functional inhibition after injecting tetanus toxin either in the motor or
      sensory cortex of adult rats by using a paired-pulse paradigm as a measure of
      excitatory and inhibitory drive. Tetanus toxin injection into the motor cortex
      (n=10) induced a marked, long-lasting reduction in inhibition which was highly
      significant in most parts of the injected cortical area. Injections into the
      sensory cortex, however, showed less marked changes in inhibition which were more
      widespread and significant only in 3 of 14 animals injected. These results give
      further evidence for a prominent effect of tetanus toxin on functional inhibition
      and strengthen the idea of a differential effect in separate cortical areas. They
      may be accounted for by the different cytoarchitecture of cortical areas with
      variable inhibitory and excitatory intracortical connections.

PMID- 9914446
TI  - Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced
      behavioral sensitization: effects on hippocampal type II corticosteroid
      receptors.
AB  - Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the
      behavioral sensitization induced by successive D-amphetamine administrations (0.5
      mg/kg) as estimated by increasing values of locomotor activity. EGb761
      pretreatment also prevented the reduced density of [3H]dexamethasone binding
      sites in the dentate gyrus and the CA1 hippocampal regions of D-amphetamine
      treated animals. These observations suggest that EGb761, by reducing
      glucocorticoid levels, could modulate the activity of the neuronal systems
      involved in the expression of the behavioral sensitization.

PMID- 9914447
TI  - Pretreatment with intravenous FGF-13 reduces infarct volume and ameliorates
      neurological deficits following focal cerebral ischemia in rats.
AB  - Fibroblast growth factor-13 (FGF-13), novel member of FGF family has recently
      been molecularly cloned as a result of high throughput sequencing of a ovarian
      cancer cell, hippocampal, and kidney cDNA libraries. The human gene encodes for a
      protein with a molecular weight of 22 kDa that is most homologous to FGF-8 (70%
      similarity). In the current study, we tested the effects of intravenously
      administered FGF-13 in a model of permanent focal cerebral ischemia in Sprague
      Dawley rats. FGF-13 or the vehicle was administered systematically via the tail
      vein 30 min prior, and 30 min and 24 h after the occlusion of the left middle
      cerebral artery (MCAo). Animals were weighed and evaluated behaviorally prior to
      and at 24 and 48 h after MCAo. The volume of cerebral infarct and swelling were
      determined using an image analysis system (BioQuant) and cresyl violet stained
      sequential sections from the forebrain region. Histopathology was evaluated to
      compare the therapeutic effects. We found a 63% reduction in infarct volume in
      FGF-13- vs. vehicle-treated animals (infarct volume was 21.9+/-3.8% in vehicle-
      and 8.1+/-1.6% in FGF-13-treated rats, p=0.0016) and a moderate inhibition of
      brain swelling by FGF-13. The reduction in infarct volume and brain swelling were
      associated with improvement of clinical deficits in FGF-13 treated animals
      (p<0.001). Histopathological examination determined that nervous tissue was
      better preserved in FGF-13 treated rats than those of controls. These data show
      that pretreatment with intravenous FGF-13 reduces infarct size and ameliorates
      neurological deficits following permanent focal cerebral ischemia in rats.

PMID- 9914448
TI  - Electron microscopic demonstration of nick end-labeled DNA fragments during
      capsaicin-induced apoptosis of trigeminal primary neurons in neonatal rats.
AB  - DNA fragmentation was induced in the trigeminal ganglion of newborn rats by
      subcutaneous capsaicin injection (50 mg/kg). Twenty-four hours later, numerous
      roundish profiles were intensely labeled by both a DNA polymerase I-mediated nick
      translation method and a terminal transferase-mediated tailing method. Direct
      electron microscopic examination of labeled profiles indicated that the labeled
      profiles were neurons at earlier stages of apoptosis. DNA fragmentation signal
      was first detected in the nucleoplasm and later spread to the cytoplasm. The cell
      finally disintegrated forming many small apoptotic bodies. DNA fragmentation
      signal in the apoptotic bodies was readily labeled by the tailing but not the
      translation method.

PMID- 9914449
TI  - The effects of chronic lead exposure on long-term depression in area CA1 and
      dentate gyrus of rat hippocampus in vitro.
AB  - Long-term potentiation (LTP) and long-term depression (LTD), two forms of
      synaptic plasticity, are believed to underlie the mechanisms of learning and
      memory. Previous studies have demonstrated that low-level lead exposure can
      impair the induction and maintenance of LTP in vivo and in vitro. The present
      study was carried out to investigate whether the low-level lead exposure affected
      the induction and maintenance of LTD. Neonatal Wistar rats were exposed to lead
      from parturition to weaning via milk of dams drinking 0.2% lead acetate solution.
      Field excitatory postsynaptic potentials (EPSPs) were recorded in hippocampal
      slices in adult rats (50-65 days) to study the alterations of LTD in area CA1 and
      dentate gyrus (DG) of hippocampus following chronic lead exposure. The input
      output (I/O) curves before conditioning in both areas showed no evident
      alterations in basic synaptic transmission between the control and lead exposure
      groups. In area CA1, the mean amplitude of EPSP slope in control rats (61+/-11%,
      n=15) decreased significantly greater than that in lead-exposed rats (78+/-8%,
      n=8, P<0.05) following low frequency stimulation (LFS, 1 Hz, 15 min), which
      lasted at least 45 min. In area DG, with application of the same LFS, the LTD was
      induced in control rats (72+/-22%, n=8), while the LFS failed to induce LTD in
      lead-exposed rats (100+/-26%, n=8). These results showed that chronic lead
      exposure affected the induction of LTD in both area CA1 and DG. The effect of
      lead on synaptic plasticity in area CA1 was also investigated. The alteration of
      the amplitude of LTP in hippocampal slices caused by lead was reexamined in order
      to compare with that on LTD (control: 189+/-23, n=5; lead-exposed: 122+/-12,
      n=10). The result demonstrated that low-level lead exposure could reduce the
      range of synaptic plasticity, which might underlie the dysfunction of learning
      and memory caused by chronic lead exposure.

PMID- 9914450
TI  - Increased number of galanin-neurons in the paraventricular hypothalamic nucleus
      of neonatally overfed weanling rats.
AB  - Perinatal overfeeding is a risk factor for overweight and diabetes during life.
      Underlying pathophysiological mechanisms are unclear. The peptide galanin is
      suggested to stimulate food intake by acting within the paraventricular
      hypothalamic nucleus (PVN). In early postnatally overfed rats overweight and
      hyperinsulinemia were observed, accompanied by an increased number of galanin
      positive neurons in the PVN at weaning. Our results might indicate malformation
      of hypothalamic galaninergic neurons due to neonatal overfeeding and
      hyperinsulinism, respectively, in rats.

PMID- 9914451
TI  - Antisense oligonucleotide treatment reveals a physiologically relevant role for
      adrenomedullin gene products in sodium intake.
AB  - Adrenomedullin (AM), a potent hypotensive peptide, is produced in numerous
      tissues including adrenal gland, kidney, brain and pituitary gland, where it acts
      to modify sodium homeostasis. Central AM administration dose-dependently inhibits
      sodium appetite. AM antisense oligonucleotide treatment significantly lowered
      peptide content in the hypothalamic paraventricular (PVN) nucleus and exaggerated
      the consumption of sodium. These results support a physiologic role for
      adrenomedullin gene products in the central regulation of sodium homeostasis.

PMID- 9914452
TI  - Activation of microglial cells by PrP and beta-amyloid fragments raises
      intracellular calcium through L-type voltage sensitive calcium channels.
AB  - The prion protein (PrP) and the amyloid beta (Abeta) precursor protein (APP) are
      two normal proteins constitutively synthesised in human brain. An altered form of
      PrP accumulates in Creutzfeldt-Jakob disease, while Abeta is involved in the
      pathogenesis of Alzheimer's disease. Synthetic fragments of both proteins, PrP106
      126 and beta25-35 (beta25-35), have been demonstrated to induce neurodegeneration
      and microglia activation. This study was undertaken to compare PrP106-126 and
      beta25-35 capability of activating human resting microglial cells. Our results
      show that both peptides are able to induce microglial activation and to elicit an
      increase in [Ca2+]i levels in cells loaded with calcium-green 1. Inhibitors of L
      type voltage-sensitive calcium channels (verapamil, nifedipine and diltiazem)
      prevented the increase in [Ca2+]i concentration as observed after treatment with
      PrP106-126 and beta25-35, thus indicating a transmembrane calcium influx through
      these channels. In addition, verapamil abolished the proliferative effect of both
      PrP106-126 and beta25-35.

PMID- 9914453
TI  - The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma
      cells.
AB  - Neurodegenerative disorders are characterized by a massive loss of nerve cells.
      The neuronal cell death is accompanied by an increased cholesterol release and
      conversion of cholesterol into the polar metabolite, 24-hydroxycholesterol (24-OH
      Chol), appears to be an important mechanism in the central nervous system for
      eliminating cholesterol from the brain. We tested the influence of 24-OH-Chol on
      SH-SY5Y human neuroblastoma cells by recording cell morphology, Trypan blue
      exclusion, LDH-release into the culture medium, intracellular calcium and
      reactive oxygen species (ROS). The exposure of SH-SY5Y human neuroblastoma cells
      to 50 microM 24-OH-Chol led to a 90% loss in cell viability within 30 h, the LDH
      release into the medium increased rapidly after 24 h, and after 24 to 30 h we
      found an elevation in intracellular calcium. These results show that, in a
      physiological concentration range, 24-OH-Chol damages neuronal cells, thus we
      speculate that this oxysterol may be involved in the etiology of
      neurodegenerative disease.

PMID- 9914454
TI  - Neuroprotective effects of growth/differentiation factor 5 depend on the site of
      administration.
AB  - Growth/differentiation factor 5 (GDF5) is a neurotrophin which protects the rat
      nigrostriatal dopaminergic pathway from 6-hydroxydopamine-induced damage. Here we
      used amphetamine-induced rotational testing, high-performance liquid
      chromatography and immunocytochemistry to investigate the minimum effective dose
      of GDF5. We also compared the effectiveness of injecting GDF5 into either the
      substantia nigra pars compacta (SNpc), the lateral ventricle (LV) or the striatum
      (or combinations of these sites).

PMID- 9914455
TI  - Medium-frequency oscillations dominate the inspiratory nerve discharge of
      anesthetized newborn rats.
AB  - In this study we examined the synchronization of the discharge of phrenic and
      recurrent laryngeal motoneurons in anesthetized rat pups 14 to 36 days of age and
      kittens, 14-15 days old. We found that the inspiratory nerve activity consisted
      of synchronized bursts separated by 20-35 ms, corresponding to medium-frequency
      oscillations (MFO). Accordingly, the autospectra of the neurograms had two peaks,
      one at the respiratory rate and the other between 22. 8-43.0 Hz. No significant
      coherence was found between MFOs in the discharges of different nerves. High
      frequency oscillations (HFO) characteristic for the adult inspiratory nerve
      activity were not present in the newborn rats. These findings demonstrate that
      phrenic nerve discharge of rat pups, like that of kittens and piglets, is in the
      MFO range, and suggest that MFO activity is an index of an early developmental
      stage of the respiratory system.

PMID- 9914457
TI  - An overview of the fifth-generation implantable cardioverter defibrillator.
AB  - It has been established that treatment with an implantable cardioverter is
      effective for life-threatening arrhythmia including ventricular tachycardia (VT)
      and ventricular fibrillation (VF). Although most third and fourth-generation
      implantable cardioverter defibrillator (ICD) models are effective for the
      treatment of VT and VF, they often misinterpret supraventricular tachycardia
      (SVT), and the incidence of inappropriate therapy delivered is as high as 20 to
      40%. To solve this clinical problem, the dual-chamber ICD was developed.
      According to the current reports on a study of the main fifth-generation ICD
      models that have been clinically used, 86 to 100% sensitivity regarding
      discrimination was obtained. In addition, the sensitivity for delivering
      appropriate therapy for VT was 97 to 100%. Since the indications for ICD therapy
      are being expanded, additional improvement of the device and adequate patient
      selection are recommended.

PMID- 9914458
TI  - Surgery for achalasia: long-term results in operated achalasic patients.
AB  - Achalasia is a functional disorder of the alimentary tract due to decreased or
      absent peristalsis of the esophageal body and obstructive outlet of the
      esophagus. Surgical treatment, eg. esophagomyotomy of the lower esophageal
      sphincter (LES), was one choice for resolving the problem and its effect was
      affirmative from reviews of many internationally authorized articles. However,
      few reports have ever questioned the long-term effects of it. From January 1968
      to May 1996, 159 esophageal achalasic patients, 90 males and 69 females, were
      admitted due to dysphagia or food regurgitation. One hundred and forty-five
      patients had received 158 operations related to this benign motor disorder. The
      majority of patients received either modified Heller esophagomyotomy (M) or M
      plus modified Belsy Mark IV antireflux procedure (M+W) for primary treatment of
      their esophageal disorder, while conditional selection with addition of
      esophageal resection as advanced procedures for failure of primary surgery. We
      retrospectively studied these patients, collected their preoperative and
      postoperative clinical results, analyzed the causes of recurrent symptoms,
      compared the long-term results in different surgical procedures and searched for
      the pathogenesis of their failure. The results disclosed that the overall success
      rate for both methods was 73.1% with 85.7% for patients receiving M+W (56) and
      64.9% of M (77) only. Through long-term follow-up, we had an improvement rate of
      97.4% at an early stage and 53.3% for M at a late stage and 98.4% and 55.6% for
      M+W, respectively. The postoperative natural course of achalasic patients could
      be seen and progressive deterioration of the operated patients with time was
      noted. Several factors might contribute to the causes of unsuccessful surgery. We
      summarized them as incomplete myotomy, fused or healed myotomy, gastroesophageal
      reflux (GER), mucosal hernia and co-combined antireflux procedure by
      hypercalibrated or floppy wrapping. Esophagomyotomy or myotomy plus antireflux
      procedure for the esophagus could be concluded to rather effective in the long
      term but palliative treatments for achalasia chronic deterioration of the results
      could be found for both of them. Defective myotomy and GER may be the major
      causes for their failure. The choice of types of surgery between M and M+W was
      not the cause of the unsuccessful results whereas the operative strategy and
      procedures would have a certain significance on the long-term effect.

PMID- 9914459
TI  - Tracheal reconstructions.
AB  - Surgical reconstruction of the trachea is a relatively complex procedure. We had
      20 cases of tracheal stenosis. We have a modest experience of 16 tracheal
      reconstructions for acquired tracheal stenosis. Two patients underwent laser
      treatment while another two died before any intervention. The majority of these
      cases were a result of prolonged ventilation (14 cases), following
      organophosphorous poisoning (11 cases), Guillain-Barre syndrome, bullet injury,
      fat embolism and surprisingly only one tumor, a case of mucoepidermoid carcinoma,
      who had a very unusual presentation. There were 12 males and 4 females in this
      series, age ranging from 12-35 years. The duration of ventilation ranged from 1
      21 days and the interval from decannulation to development of stridor was between
      5-34 days. Six of them were approached by the cervical route, 5 by thoracotomy
      and cervical approach, 2 via median sternotomy and 3 by thoracotomy alone. Five
      of them required an additional laryngeal drop and 1 required pericardiotomy and
      release of pulmonary veins to gain additional length. The excised segments of
      trachea measured 3 to 5 cms in length. All were end to end anastomosis with
      interrupted Vicryl sutures. We have had no experience with stents or prosthetic
      tubes. Three patients developed anastomotic leaks which were controlled
      conservatively. Almost all of them required postoperative tracheo-bronchial
      suctioning with fibreoptic bronchoscope. We had one death in this series due to
      sepsis.

PMID- 9914460
TI  - Natriuretic peptides in the lung modulated by pneumonectomy.
AB  - BACKGROUND: Natriuretic peptides are vasodilator hormones involved in the
      regulation of blood pressure and volume homeostasis. However, the mechanism of
      these peptides after pneumonectomy remains obscure. METHODS: We investigated
      changes in the pulmonary arterial pressure and the localization and changes in
      the atrial (A-type) natriuretic peptide (ANP) and the C-type natriuretic peptide
      (CNP) in the lung, using immunohistochemistry and radioimmunoassay (RIA) in
      anesthetized dogs. Furthermore, we examined guanosine 3', 5'-monophosphate (cGMP)
      levels in plasma and in the contralateral lung. RESULTS: Pulmonary arterial
      pressure was significantly increased after pneumonectomy. The immunoreactivities
      of both ANP and CNP were detected in the endothelium of the pulmonary artery. In
      the contralateral lung, the concentrations of ANP and CNP were both significantly
      increased. In plasma, only ANP levels were significantly increased. In contrast,
      the plasma and lung cGMP levels were significantly reduced after pneumonectomy.
      CONCLUSIONS: We postulate that the processes from secretion in the vascular
      endothelial cells to the action via ANP and CNP receptors are effected in the
      contralateral lung tissue at the acute stage of pneumonectomy.

PMID- 9914461
TI  - Integrity of the pericardium. Its beneficial effects on the protection of the
      right ventricle in the presence of acute pulmonary hypertension.
AB  - After cardiac transplant (CT), the right ventricle can be subject to an acute
      pressure overload, especially in cases where there is a pre-existing severe
      pulmonary hypertension. OBJECTIVES: To determine the maximum tolerance of the
      right ventricle (MxTRV) when faced with acute pressure overload. To study the
      function of both ventricles of the healthy heart (donor) when faced with
      different degrees of pulmonary hypertension. To detect possible interactions
      between the ventricles in the absence of the pericardium to approximate the
      experimental model to the clinical model of CT. METHODS: The pulmonary artery is
      progressively constrained in an experimental model until biventricular failure is
      detected. This experiment is performed in two different situations: with and
      without pericardial integrity. RESULTS: When pericardial integrity is maintained
      the MxTRV faced with a pressure overload is 73.2+/-8.56 mmHg. When this pressure
      is exceeded there is a circulatory collapse with a sharp fall in the cardiac
      output and in the aortic pressure. However, when pericardectomy is performed
      (model similar to CT), only 52+/-6.71 mmHg is tolerated (p< 0.001). CONCLUSIONS:
      With the pericardium open, as in CT, the maximum pressure that the right
      ventricle can support is significantly less than with the pericardium closed. The
      pericardium has a positive effect in protecting the systolic ventricular
      interaction.

PMID- 9914462
TI  - Left ventricular free wall rupture following mitral valve replacement.
AB  - During a 10-year period, 110 patients underwent mitral valve replacement (MVR).
      We experienced three left ventricular ruptures among these patients. Two had a
      type I immediate rupture, and one had a type III delayed rupture. Two patients
      (type I, III) survived after repair of the rupture. It was possible to control
      bleeding by manual compression with oxidized cellulose, collagen mat and fibrin
      glue with or without external mattress sutures. Following the repair, an intra
      aortic balloon pump and sedative agents were used in both patients. In the other
      patient with a type I early rupture, control of bleeding was attempted by
      external direct suture using Teflon felt. The bleeding was controlled by this
      repair and the use of a left ventricular assist device, but the patient died of a
      brain infarction 5 days after the operation. The manual compression technique
      using oxidized cellulose, collagen mat and fibrin glue may be useful for minor
      lacerations, and for reinforcing repairs. The intra-aortic balloon pump and
      continuous sedation are useful for unloading the ventricle and reducing the
      tension on repairs.

PMID- 9914464
TI  - Screening the thoracic aorta for atheroma: a comparison of manual palpation,
      transesophageal and epiaortic ultrasonography.
AB  - Accurate detection of atheroma within the thoracic aorta is an important part of
      most stroke prevention strategies in cardiac surgery. The thoracic aorta was
      divided into six zones corresponding to sites of surgical manipulation. Zones 1
      3, proximal, mid and distal ascending aorta, zones 4-5, proximal and distal arch
      and zone 6, proximal descending aorta. This study compares the accuracy of
      atheroma detection by manual palpation, epiaortic (EPI) and transesophageal (TEE)
      ultrasonography in 70 patients. RESULTS: Using EPI as the reference method for
      zones 1-4, 14/70 patients were identified with moderate or severe atheroma. The
      frequency of atheroma was age related with the youngest at 55 years. Compared
      with EPI, manual palpation correctly detected moderate or severe atheroma in 7/14
      patients (p=0.0058) and TEE in only 4/14 patients (p= 0.0002). For TEE, adequate
      imaging was only obtained in 41/70 in zone 3 and 30/70 in zone 4. Adequate
      imaging of zones 5-6 was obtained in all patients using TEE. Of 68 patients with
      adequate imaging of all zones, 36 had moderate or severe atheroma in zones 5-6.
      The positive predictive value for zones 1-4 based on atheroma in zones 5-6 was
      39%. Of 32 patients with nil or mild atheroma in zones 5-6, only 1 had moderate
      or severe atheroma in zones 1-4 (negative predictive value 94%). CONCLUSION:
      Manual palpation and TEE are inaccurate methods of atheroma detection in zones 1
      4. Epiaortic ultrasonography is recommended for all patients undergoing cardiac
      surgery, although the yield will be low for patients < 50 years of age or if
      there is nil or mild atheroma detected by TEE in zones 5-6.

PMID- 9914463
TI  - Post-operative effects of olprinone after coronary artery bypass grafting.
AB  - The aim of this study was to test the effects of olprinone after coronary artery
      bypass grafting (CABG). In order to prevent hypotension caused by olprinone, low
      doses of catecolamines were used concomitantly. Total 22 elective CABG cases were
      evaluated. In all cases, moderate hypothermia and cardioplegic cardiac arrest
      were performed. In 10 cases, continuous intravenous 0.1 microg/kg/min of
      olprinone, 3 microg/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial
      doses, were used concomitantly (Group I). As a control, the same initial doses of
      catecolamine (DOB and DOA) of Group I were administered in another 12 patients
      (Group II). When the pump flow of cardiopulmonary bypass (CPB) was decreased to
      half, these drugs were administered in both groups. Hemodynamics were recorded
      before CPB, just after the operation and 3, 6, 12, 24, 48, and 72 hours after the
      operation. Three hours after the operation, both mean aortic pressure (AoP) and
      pulmonary artery pressures (PAP) of Group I demonstrated significantly lower
      values than those of Group II. Cardiac index (CI) of Group I showed significantly
      higher values than that of Group II until 6 hours after surgery. The systemic
      vascular resistance index (SVRI) of Group I indicated a significantly lower value
      than that of Group II until 24 hours after the operation. Pulmonary capillary
      wedge pressure (PCWP) of Group I demonstrated a significantly lower value than
      that of Group II. There were no significant differences in urine output, oxygen
      delivery (DO2) and oxygen consumption (VO2) between both groups. Olprinone
      increased CI and decreased SVRI, and it showed easy weaning from CPB,
      demonstrating excellent hemodynamics after CABG. These results suggested that
      this new phosphodiesterase inhibitor may be effective for not only weaning from
      CPB but also post-cardiotomy cardiogenic shock.

PMID- 9914465
TI  - Thoracoscopic resection of a giant leiomyoma of the esophagus with a mediastinal
      outgrowth.
AB  - We reported a case of a 20-year-old man with a giant leiomyoma of the esophagus
      resected under video-assisted thoracic surgery (VATS). The patient demonstrated
      an abnormal shadow on a chest x-ray and a posterior mediastinal tumor 11 cm in
      diameter on a computed tomogram (CT) and on magnetic resonance imaging (MRI). A
      leiomyoma or a neurogenic tumor of the esophagus was suspected, and VATS was
      performed. The resected tumor was pathologically confirmed to be a leiomyoma of
      the esophagus. A giant esophageal leiomyoma showing extraluminal outgrowth should
      be treated by VATS.

PMID- 9914466
TI  - Anterior ischemic optic neuropathy: a complication after extracorporal
      circulation.
AB  - INTRODUCTION: Anterior ischemic optic neuropathy (AION) describes a defect of the
      optic nerve leading to irreversible loss of vision in most cases. Pathophysiology
      of this disease is manifold and has been discussed as a posthemorrhagic
      complication as well as a neurological complication after operations with
      cardiopulmonary bypass. METHODS: On the basis of two cases, the clinical picture
      is described in relation to the available literature. Preoperative risk factors,
      operative data, cardiopulmonary-bypass, postoperative complications and clinical
      symptoms are discussed together with ophthalmologic findings in order to
      elucidate the pathophysiology of this process. RESULTS: There is no reliable and
      effective treatment of anterior ischemic optic neuropathy. Neither
      corticosteroids, osmotic diuretics, hemodilution nor surgical decompression of
      the optic nerve have proved successful. Hence, measures to avoid ischemic optic
      neuropathy have priority. The following risk factors were determined: History of
      glaucoma or other ophthalmological problems, prolonged cardiopulmonary bypass
      time and myocardial ischemia, general oedema during cardiopulmonary bypass,
      excessive hemodilution with low hemoglobin and hematocrit, hypo- or hypertension,
      systemic hypothermia, need for vasoactive medication. CONCLUSIONS: Influenced by
      a variety of factors, pathophysiological microvascular changes provoke anterior
      ischemic neuropathy with sudden painless loss of vision, irreversible in most
      cases. Since therapeutic trials have failed, prevention of possible causes is the
      only way to avoid this rare but severe complication of cardiac surgery.

PMID- 9914468
TI  - Editorial 

PMID- 9914467
TI  - Congenital coronary artery fistula treated surgically in the right atrium and the
      atrial septum.
AB  - Various surgical techniques have been employed according to the type of the
      coronary fistula. In this case, preoperative examinations by aortography and MRI
      revealed a coronary artery fistula which originated from a site just proximal of
      the RCA, ran through the interatrial septum and drained into the posterior wall
      of right atrium. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 1. 95.
      During surgery, we were not able to ligate or divide the fistula on the cardiac
      surface because the fistulous vessel originated from the posterior aspect of the
      proximal RCA. After establishing a cardiopulmonary bypass, the opening of the
      fistula in the right atrium was closed with an autologous pericardium patch, the
      surface of the interatrial septum was incised and the fistula was identified. The
      conduit was then divided and closed in the atrial septum. The postoperative
      course was uneventful. This approach is able to interrupt the fistula safely
      without interfering with normal coronary flow. Closure of the outlet and division
      of the fistula itself is a recommendable method to insure interruption of
      fistulous communication.

PMID- 9914469
TI  - Molecular mechanisms and regulation of insulin exocytosis as a paradigm of
      endocrine secretion.
AB  - Secretion of the peptide hormone insulin from pancreatic beta cells constitutes
      an important step in the regulation of body homeostasis. Insulin is stored in
      large dense core vesicles and released by exocytosis, a multistage process
      involving transport of vesicles to the plasma membrane, their docking, priming
      and finally their fusion with the plasma membrane. Some of the protein components
      necessary for this process have been identified in beta cells. The export of
      potent and potentially harmful substances has to be tightly controlled. The
      secretory response in pancreatic beta cells requires the concerted action of
      nutrients together with enteric hormones and neurotransmitters acting on G
      protein coupled receptors. It is well established that glucose and other
      metabolizable nutrients depolarize the beta-cell membrane and the ensuing Ca2+
      influx through voltage-dependent channels constitutes a main stimulus for insulin
      exocytosis. Theoretical considerations and recent observations suggest in
      addition an organizing role for the Ca2+ channel similar to neurotransmission. A
      second regulatory control on exocytosis is exerted by monomeric and
      heterotrimeric G-proteins. The monomeric GTPase Rab3A controls insulin secretion
      through cycling between a guanosine triphosphate liganded vesicle-bound form and
      a guanosine diphosphate liganded, cytosolic form. The effect of neurohormones is
      transduced by the heterotrimeric GTPases. Whereas pertussis-toxin sensitive alpha
      subunits exert direct inhibition at the level of exocytosis, the Gbeta gamma
      subunits are required for stimulation. It is possible that these GTPases exert
      immediate regulation, while protein kinases and phosphatases may modulate long
      term adaptation at the exocytotic machinery itself. The molecular nature of their
      activators and effectors still await identification. Insights into the
      progression of the exocytotic vesicle from docking to fusion and how these
      processes are precisely regulated by proteins and second messengers may provide
      the basis for new therapeutic principles.

PMID- 9914470
TI  - Membrane fluidization by ether, other anesthetics, and certain agents abolishes P
      glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells.
AB  - The anesthetics benzyl alcohol and the nonaromatic chloroform and diethyl ether,
      abolish P-glycoprotein (Pgp) ATPase activity in a mode that does not fit
      classical competitive, noncompetitive, or uncompetitive inhibition. At
      concentrations similar to those required for inhibition of ATPase activity, these
      anesthetics fluidize membranes leading to twofold acceleration of doxorubicin
      flip-flop across lipid membranes and prevent photoaffinity labeling of Pgp with
      [125I]-iodoarylazidoprazosin. Similar concentrations of ether proved nontoxic and
      modulated efflux from Pgp-overexpressing cells. A similar twofold acceleration of
      doxorubicin flip-flop rate across membranes was observed with neutral mild
      detergents, including Tween 20, Nonidet P-40 and Triton X-100, and certain Pgp
      modulators, such as verapamil and progesterone. Concentrations of these agents,
      similar to those required for membrane fluidization, inhibited Pgp ATPase
      activity in a mode similar to that observed with the anesthetics. The mode of
      inhibition, i.e. lack of evidence for classical enzyme inhibition and the
      correlation of Pgp ATPase inhibition with membrane fluidization over a wide range
      of concentrations and structures of drugs favors the direct inhibition of Pgp
      ATPase activity by membrane fluidization. The unusual sensitivity of Pgp to
      membrane fluidization, as opposed to acceleration of ATPase activity of ion
      transporters, could fit the proposed function of Pgp as a 'flippase', which is in
      close contact with the membrane core.

PMID- 9914471
TI  - Preferential inhibition of inducible nitric oxide synthase in intact cells by the
      4-amino analogue of tetrahydrobiopterin.
AB  - In the present study we demonstrate that the 4-amino analogue of
      tetrahydrobiopterin, 2,4-diamino-5,6,7,8-tetrahydro-6-(l-erythro-1, 2
      dihydroxypropyl)pteridine (4-amino-H4biopterin) binds with high affinity to
      recombinant endothelial NO synthase and concomitantly inhibits enzyme activity
      [IC50 = 14.8 +/- 7.5 microm in the presence of added 5,6,7,8-tetrahydro-l
      erythrobiopterin (H4biopterin) 10 microm] as efficiently as previously shown for
      inducible NO synthase [Mayer, B., Wu, C.Q., Gorren, A.C.F., Pfeiffer, S.,
      Schmidt, K., Clark, P., Stuehr, D.J. & Werner, E.R. (1997) Biochemistry 36, 8422
      8427]. In cultured porcine endothelial cells, however, 4-amino-H4biopterin was
      less effective in inhibiting NO formation (IC50 = 420 +/- 36 microm) as compared
      with inhibition of the inducible isoform in murine fibroblasts (IC50 = 15 +/- 4.9
      microm) and in human DLD-1 adenocarcinoma cells (IC50 = 55 +/- 10.3 microm). In
      all cells investigated, the inhibitory effect of 4-amino-H4biopterin was markedly
      enhanced by depletion of intracellular H4biopterin and could be overcome by
      increasing intracellular H4biopterin concentrations. Endothelial cells contained
      lower amounts of H4biopterin [5.2 +/- 0.3 pmol.(mg protein)-1] than fibroblasts
      [19.4 +/- 2.7 pmol.(mg protein)-1] and DLD-1 cells [8.3 +/- 1.1 pmol.(mg protein)
      1], so that the selectivity of 4-amino-H4biopterin towards inducible NO synthase
      was not explained by differences in the H4biopterin levels. Because 4-amino
      H4biopterin did not suppress expression of NO synthase in cytokine-treated cells,
      we suggest that high-affinity binding of the inhibitor during protein expression
      may be responsible for the preferential inhibition of the inducible isozyme in
      intact cells.

PMID- 9914472
TI  - Oxidative modification of high-density lipoprotein 3 induced by human
      polymorphonuclear neutrophils. Protective effect of pentoxifylline.
AB  - The function of high-density lipoproteins (HDLs) in reverse cholesterol transport
      is impaired if HDLs are subjected to oxidative stress. Polymorphonuclear
      neutrophils (PMNs), which have been detected in the earliest stages of
      atherosclerotic lesions, are one of the most likely sources of the reactive
      oxygen species that cause such stress. In this study, we investigated the effect
      of a PMN oxidative burst on HDL3. We also studied the impact on these events of
      pentoxifylline, a drug that regulates granulocyte function. HDL3 (370 nmol.mL-1
      cholesterol-HDL) was incubated with PMNs (2 x 106. mL-1) in NaCl/Pi in the
      presence or absence of an iron chelate complex (10 microm Fe-nitrilotriacetic
      acid) at 37 degreesC for 60 min or 24 h. Phorbol myristate acetate (PMA) or
      formyl-methionylleucyphenylalanine (fMetLeuPhe) was used to stimulate PMNs. In
      iron-free NaCl/Pi medium, PMA-stimulated PMNs had a 40% lower HDL3 alpha
      tocopherol content, whatever the incubation time. In NaCl/Pi medium containing
      iron, there was 80% less HDL3 alpha-tocopherol at 60 min, and HDL3 alpha
      tocopherol had almost disappeared after 24 h. In this latter condition, the
      amount of thiobarbituric acid-reactive substances was significantly higher than
      the respective control HDL3 (P < 0.05) and oxidation of HDL3 by PMA-stimulated
      PMNs was associated with cross-linking of apoprotein AI, which was detected by
      SDS/PAGE. Similar results were obtained with fMetLeuPhe-stimulated PMN except
      that HDL3 alpha-tocopherol was consumed much more slowly during the first 60 min.
      Pretreatment of PMNs with various concentrations of pentoxifylline (0.001-20 mm)
      led to the concentration-dependent inhibition of oxidative modification of HDL3
      induced by stimulated PMNs. The addition of 20 mm pentoxifylline in the most
      extreme oxidative stress conditions resulted in 70% of HDL3 alpha-tocopherol
      being maintained, with no formation of thiobarbituric acid-reactive substances
      and a lower level of apoprotein AI cross-linking. Thus HDL3 is susceptible to
      oxidative modifications induced by stimulated PMNs, in the presence of an
      exogenous source of iron. Pentoxifylline inhibited the oxidative modification of
      HDL3 by PMNs.

PMID- 9914473
TI  - Local cytokines induce differential expression of matrix metalloproteinases but
      not their tissue inhibitors in human endometrial fibroblasts.
AB  - The endometrium is the only human tissue to undergo cyclic breakdown and
      regeneration. This physiological alternation renders it an advantageous system
      for studying tissue remodelling. Our previous observations indicate that
      menstrual endometrial breakdown is initiated by matrix metalloproteinases (MMPs),
      which are controlled overall by ovarian steroids but are also locally regulated
      by cytokines. We have therefore compared the effect of several endometrial
      cytokines on the gene expression of eight MMPs and their tissue inhibitors (TIMP)
      1, -2 and -3, in primary cultures of human endometrial fibroblasts. Three
      categories of gene expression were identified: (a) MMP-13, -15 and -16 mRNAs were
      not detected despite stimulation by various cytokines; (b) MMP-2 and -14 as well
      as TIMP-1, -2 and -3 mRNAs were constitutively expressed but not markedly
      affected by the six cytokines tested; (c) mRNAs for MMP-1, -9 and -11 were
      selectively induced by specific cytokines: insulin-like growth factor-II,
      epidermal growth factor (EGF), platelet derived growth factor (PDGF)-BB and
      interleukin (IL)-6 stimulated MMP-11 expression; MMP-1 was induced by EGF, PDGF
      BB, tumour necrosis factor (TNF)alpha and IL-1alpha, which also exerted additive
      effects. In contrast with MMP-1 and MMP-11 gene expression, which was sustained
      for 48 h, MMP-9 mRNA was quickly induced by TNFalpha, but disappeared within 12 h
      despite continuing stimulation. These results show that several cytokines are
      able to induce the selective expression of MMPs in cultured human endometrial
      fibroblasts and are thus good candidates for involvement in local triggering of
      menstrual tissue breakdown.

PMID- 9914474
TI  - Distinct promoters control transmembrane and cytosolic protein tyrosine
      phosphatase epsilon expression during macrophage differentiation.
AB  - We have recently isolated two cDNAs encoding two forms of transmembrane and
      cytosolic protein tyrosine phosphatase epsilon (PTPepsilon). In this study, the
      5' end of the rat PTPepsilon gene was isolated and characterized. Transmembrane
      PTPepsilon (PTPepsilonM) and cytosolic PTPepsilon (PTPepsilonC) were encoded by a
      single gene. 5' RACE analysis and RNase protection assay showed that the mRNA of
      each PTPepsilon isoform was transcribed from different promoters. The putative
      promoter regions of two alternative first exons lacked a TATA box, but contained
      potential recognition sites for several transcription factors. Reverse
      transcription PCR analysis revealed that PTPepsilonC mRNA was up-regulated during
      interleukin 6-induced differentiation of murine leukemia M1 cells, whereas
      PTPepsilonM mRNA was down-regulated. With the use of luciferase as a reporter
      gene, the promoter activities of the 5'-flanking regions were examined during
      phorbol myristate acetate-induced differentiation of HL-60 cells. In the
      differentiated HL-60 cells, the activity of the PTPepsilonC promoter, but not
      that of PTPepsilonM, was dramatically elevated. Furthermore, we found that
      PTPepsilonC mRNA is highly expressed in mouse peritoneal macrophages and enhanced
      during activation by lipopolysaccharide. These results suggest that the different
      promoters control expression of PTPepsilon isoforms during the differentiation
      and/or activation of macrophages.

PMID- 9914475
TI  - The role of the fourth extracellular domain of the rat corticotropin-releasing
      factor receptor type 1 in ligand binding.
AB  - The role of the fourth extracellular loop (e4) of rat corticotropin-releasing
      factor (CRF) receptor, type 1, in ligand binding was investigated using chimeric
      receptor molecules. e4 of CRF receptor, type 1, was replaced by the corresponding
      domains of two other G protein-coupled receptors, the rat glucagon receptor or
      the human pituitary adenylate cyclase activating polypeptide (PACAP) receptor.
      Both chimeras were transported properly to the cell membranes of transfected
      chinese hamster ovary cells as indicated by immunocytochemical analysis. Ovine
      CRF (oCRF) was bound specifically, but with low affinity (Kd = 2-5 microm).
      Cyclic AMP was not accumulated intracellularly in response to increasing
      concentrations of oCRF. Based on these data, it is concluded that e4 of rat CRF
      receptor, type 1, is involved in ligand binding. To confirm the importance of e4
      in binding CRF, three negatively charged amino acids of e4, Glu336, Asp337 and
      Glu338, were replaced by Gln, Asn and Gln, respectively. No effect on ligand
      binding and cyclic AMP accumulation was observed (Kd = 5 nm; EC50 = 1.5 nm).
      However, when Tyr346, Phe347 and Asn348 of e4 were changed to three alanine
      residues, ligand binding affinity as well as efficacy in cyclic AMP accumulation
      were significantly decreased (Kd = 64 nm; EC50 = 32 nm).

PMID- 9914476
TI  - Slow-binding and competitive inhibition of 8-amino-7-oxopelargonate synthase, a
      pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis, by
      substrate and intermediate analogs. Kinetic and binding studies.
AB  - 8-Amino-7-oxopelargonate synthase catalyzes the first committed step of biotin
      biosynthesis in micro-organisms and plants. Because inhibitors of this pathway
      might lead to antibacterials or herbicides, we have undertaken an inhibition
      study on 8-amino-7-oxopelargonate synthase using six different compounds. d
      Alanine, the enantiomer of the substrate of this pyridoxal-5'-phosphate-dependent
      enzyme was found to be a competitive inhibitor with respect to l-alanine with a
      Ki of 0.59 mm. The fact that this inhibition constant was four times lower than
      the Km for l-alanine was interpreted as the consequence of the inversion
      retention stereochemistry of the catalyzed reaction. Schiff base formation
      between l or d-alanine and pyridoxal-5'-phosphate, in the active site of the
      enzyme, was studied using ultraviolet/visible spectroscopy. It was found that l
      and d-alanine form an external aldimine with equilibrium constants K = 4.1 mm and
      K = 37.8 mm, respectively. However, the equilibrium constant for d-alanine
      aldimine formation dramatically decreased to 1.3 mm in the presence of saturating
      concentration of pimeloyl-CoA, the second substrate. This result strongly
      suggests that the binding of pimeloyl-CoA induces a conformational change in the
      active site, and we propose that this new topology is complementary to d-alanine
      and to the putative reaction intermediate since they both have the same
      configuration. (+/-)-8-Amino-7-oxo-8-phosphonononaoic acid (1), the phosphonate
      derivative of the intermediate formed during the reaction, was our most potent
      inhibitor with a Ki of 7 microm. This compound behaved as a reversible slow
      binding inhibitor, competitive with respect to l-alanine. Kinetic investigation
      showed that this slow process was best described by a one-step mechanism
      (mechanism A) with the following rate constants: k1 = 0.27 x 103 m-1.s-1, k2 =
      1.8 s-1 and half-life for dissociation t1/2 = 6.3 min. The binding of compound 1
      to the enzyme was also studied using ultraviolet/visible spectroscopy, and the
      data were consistent with the kinetic data (K = 4.2 microm). Among the other
      compounds tested, two potential transition state analogs, 4-carboxybutyl(1-amino
      1-carboxyethyl)phosphonate (4) and 2-amino-3-hydroxy-2-methylnonadioic acid (5)
      were found to be competitive inhibitors with respect to l-alanine with Ki of 68
      microm and 80 microm, respectively.

PMID- 9914477
TI  - Wheat-germ aspartate transcarbamoylase: revised purification, stability and re
      evaluation of regulatory kinetics in terms of the Monod-Wyman-Changeux model.
AB  - A revised and simplified purification scheme for aspartate transcarbamoylase
      (ATCase) from wheat-germ is reported, with an eightfold increase in scale
      (yielding approximately 10 mg of the pure protein from 4 kg of wheat-germ), and
      improved characteristics of stability and regulatory kinetics. The ATCase
      obtained is greater than 96% pure, as judged by polyacrylamide gel
      electrophoresis. The long-term stability (i.e. on a time-scale of several hours
      to weeks) of the activity of the purified enzyme, under various storage
      conditions, was investigated. At 4 degreesC and pH 7.5, stability was found to be
      strongly dependent on protein concentration (increased stability at high
      concentration), buffer concentration (decreased stability at high buffer
      concentration) and the inclusion of glycerol (increased stability with increasing
      glycerol concentration). The enzyme is routinely stored at 4 degreesC, in 0. 05 m
      Tris/HCl buffer containing 25% glycerol and at high protein concentration
      (approximately 1 mg.mL-1, or 10 microm in trimers). Under these conditions, the
      half-life of the enzyme activity is greater than 300 days. Over the time-scale of
      kinetic experiments (up to 20 min), the diluted activity (at around 1 nm of
      ATCase, in the presence of ligands) is completely stable. The specific activity
      remains constant in the range 0.1-10 nm, in the absence and presence of ligands,
      showing that dissociation of the trimeric enzyme into its subunits is negligible.
      Steady-state kinetics were examined using the enzyme at a concentration of 1.3
      nm. Initial-rate curves for both allosteric ligands, carbamoylphosphate (CP) and
      uridine 5'-monophosphate (UMP), showed pronounced sigmoidicity, each in the
      presence of the other. In the absence of UMP, initial-rate curves for CP are
      hyperbolic. The initial rate data fit reasonably well to a trimeric Monod-Wyman
      Changeux model, suggesting a two-state conformational mechanism, greatly
      favouring the active (R) state when both ligands are absent, in which the R-state
      binds CP exclusively (dissociation constant = 23.2 microm), and the T-state binds
      UMP exclusively (dissociation constant = 0.49 microm). This regulatory behaviour
      was found to be quite stable, and was indistinguishable from that of the enzyme
      in a freshly made crude extract, even after storage of the pure sample for 5
      months. This enzyme preparation is therefore free of the anomalous allosteric
      kinetics produced by a previous purification scheme, in which the affinity for
      UMP was markedly reduced, CP rate curves showed no sigmoidicity, while UMP rate
      curves had sigmoidicity exaggerated by a low maximum.

PMID- 9914478
TI  - Characterization of human T-cell leukemia virus type I integrase expressed in
      Escherichia coli.
AB  - The C-terminal part of the pol gene of the human T-cell leukemia virus type I
      (HTLV-I) is predicted to encode the integrase (IN) of the virus; however, this
      protein has not yet been detected in virions or infected cells. We expressed the
      putative IN from an infectious molecular clone of HTLV-I in Escherichia coli.
      Comparison with protein resulting from coexpression of HTLV-I protease (PR) and
      Pol in insect cells indicated that the bacterially expressed protein is identical
      with or very similar to IN released from a PR-Pol precursor by proteolytic
      cleavage. HTLV-I IN was purified from E. coli under native conditions. The
      protein behaved like a dimer in size-exclusion chromatography. It carried out
      activities characteristic of retroviral IN with high efficiency, displaying a
      strong preference for U5-derived vs. U3-derived sequences in the processing and
      strand-transfer reactions. In the disintegration reaction, HTLV-I IN not only
      accepted the double-stranded branched substrate corresponding to the product of a
      strand-transfer reaction, but was also able to carry out a phosphoryl transfer on
      a branched molecule with a single-stranded or a single adenosine overhang.

PMID- 9914479
TI  - Endoglucanase 28 (Cel12A), a new Phanerochaete chrysosporium cellulase.
AB  - A 28-kDa endoglucanase was isolated from the culture filtrate of Phanerochaete
      chrysosporium strain K3 and named EG 28. It degrades carboxymethylated cellulose
      and amorphous cellulose, and to a lesser degree xylan and mannan but not
      microcrystalline cellulose (Avicel). EG 28 is unusual among cellulases from
      aerobic fungi, in that it appears to lack a cellulose-binding domain and does not
      bind to crystalline cellulose. The enzyme is efficient at releasing short fibres
      from filter paper and mechanical pulp, and acts synergistically with
      cellobiohydrolases. Its mode of degrading filter paper appears to be different to
      that of endoglucanase I from Trichoderma reesei. Furthermore, EG 28 releases
      colour from stained cellulose beads faster than any other enzyme tested. Peptide
      mapping suggests that it is not a fragment of another known endoglucanases from
      P. chrysosporium and peptide sequences indicate that it belongs to family 12 of
      the glycosyl hydrolases. EG 28 is glycosylated. The biological function of the
      enzyme is discussed, and it is hypothesized that it is homologous to EG III in
      Trichoderma reesei and the role of the enzyme is to make the cellulose in wood
      more accessible to other cellulases.

PMID- 9914480
TI  - Affinity of the periplasmic chaperone Skp of Escherichia coli for phospholipids,
      lipopolysaccharides and non-native outer membrane proteins. Role of Skp in the
      biogenesis of outer membrane protein.
AB  - The Skp protein of Escherichia coli has been proposed to be a periplasmic
      molecular chaperone involved in the biogenesis of outer membrane proteins. In
      this study, evidence is obtained that Skp exists in two different states
      characterized by their different sensitivity to proteases. The conversion between
      these states can be modulated in vitro by phospholipids, lipopolysaccharides and
      bivalent cations. Skp is able to associate with and insert into phospholipid
      membranes in vitro, indicating that it may associate with phospholipids in the
      inner and/or outer membrane in vivo. In addition, it interacts specifically with
      outer membrane proteins that are in their non-native state. We propose that Skp
      is required in vivo for the efficient targeting of unfolded outer membrane
      proteins to the membrane.

PMID- 9914481
TI  - Purification and cloning of the mitochondrial branched-chain amino acid
      aminotransferase from sheep placenta.
AB  - This paper presents the first purification of the mitochondrial branched-chain
      amino acid aminotransferase (BCATm) from sheep placenta. It is a homodimer with
      an apparent subunit molecular mass of 41 kDa. The enzyme differs from those of
      the rat and human as it appears to form at least one intermolecular disulfide
      bond. The sheep BCATm cDNA (1.4 kb) encodes a mature polypeptide of 366 amino
      acids with a calculated molecular mass of 41 329 Da and a partial mitochondrial
      targeting sequence of seven amino acids. The sheep BCATm sequence shares higher
      identity with other mammalian BCATm isoenzymes (82-85%) than with the cytosolic
      isoenzymes (60%). By Northern blot analysis, a message of 1.7 kb was detected in
      sheep placenta and skeletal muscle. Measurements of BCAT activity, mRNA and BCATm
      protein in sheep placenta and skeletal muscle revealed that BCATm is the sole
      BCAT isoenzyme expressed in placenta, whereas it contributes 57 and 71% of the
      BCAT activity in tensor fascia latae and masseter muscles from weaned lambs
      respectively. Skeletal muscle, the main site of branched-chain amino acid
      transamination, exhibits significantly lower BCAT activity in sheep than in rat.
      Our results suggest that the low BCATm mRNA level probably accounts for the low
      BCAT activity in sheep skeletal muscle, and that the metabolic scheme for
      branched-chain amino acid catabolism is specific to each species.

PMID- 9914482
TI  - Protein interactions of Gts1p of Saccharomyces cerevisiae throughout a region
      similar to a cytoplasmic portion of some ATP-binding cassette transporters.
AB  - The GTS1 gene product, Gts1p, has pleiotropic effects on the timing of budding,
      cell size, heat tolerance, sporulation and the lifespan of the yeast
      Saccharomyces cerevisiae. In this study, we found (using the yeast two-hybrid
      system) that Gts1p forms homodimers throughout the 18-amino acid region 296-313
      which has considerable similarity to a region downstream of the Walker nucleotide
      binding motif A of some ATP-binding cassette (ABC) transporters. The region
      contains two aspartic acid residues at 301 and 310 preceded by hydrophobic amino
      acid residues, and Gts1p with an Asp310 to Ala substitution showed considerably
      reduced homodimerization, as shown by the two-hybrid assay. Overexpression of the
      point-mutated Gts1p did not efficiently induce the Gts1p-related phenotypes
      described above, suggesting that the homodimerization of Gts1p is required for it
      to function in vivo. The C-terminal cytoplasmic domain of the yeast ABC
      transporters Mdl1p (multidrug resistance-like transporter) and Ycf1p (yeast
      cadmium factor or glutathione S-conjugate pump) bound to Gts1p in the two-hybrid
      system, and the heterodimerization activity of the Gts1p with the Asp301 to Ala
      substitution was more affected than the Gts1p with the Asp310 to Ala
      substitution. Overexpression of GTS1 considerably reduced, and disruption of GTS1
      slightly decreased, cellular resistance to cycloheximide, cadmium, cisplatin and
      1-chloro-2,4-dinitrophenol, which (except for cycloheximide) are all substrates
      of Ycf1p. These results suggest that Gts1p interacts with some ABC transporters
      through the binding site overlapping that of homodimerization and modulates their
      activity.

PMID- 9914483
TI  - Primary structure and possible functions of a trypsin inhibitor of Bombyx mori.
AB  - A protein with a low molecular mass of 6027 was purified from cocoon shell of
      silkworm, Bombyx mori. Two-dimensional polyacrylamide gel electrophoresis
      (2D/PAGE) resolved this protein into a single spot with pI 4.3 and Mr 6000. Amino
      acid sequence analysis revealed that this protein consists of 55 amino acids, six
      of these being cysteine residues and is highly homologous to bovine pancreatic
      trypsin inhibitor-type inhibitors. The 6-kDa protein is heat stable and acid
      stable and inhibits bovine trypsin by forming a low-dissociation complex with
      trypsin in a 1 : 1 molar ratio (Ki = 2.8 x 10-10), but does not alpha
      chymotrypsin. This cocoon shell-associated trypsin inhibitor (CSTI) was thus
      concluded to belong to the bovine pancreatic trypsin inhibitor class. CSTI was
      developmentally regulated in the silk gland at the final stage of larval growth,
      and its specific distribution in the middle silk gland, an organ in which silk
      proteins are stored during the final larval instar, occurred before the onset of
      spinning. This inhibitor protects the tryptic degradation of fibroin light (L)
      chain in vitro. These results suggest that this trypsin inhibitor may play an
      important part on regulating proteolytic activity in the silk gland or protecting
      silk proteins from degradation during histolysis.

PMID- 9914484
TI  - Isolation, amino acid sequence determination and binding properties of two fatty
      acid-binding proteins from axolotl (Ambistoma mexicanum) liver. Evolutionary
      relationship.
AB  - Up until now, the primary structure of fatty-acid-binding proteins (FABPs) from
      the livers of four mammalian (rat, human, cow and pig) and three nonmammalian
      (chicken, catfish and iguana) species has been determined. Based on amino acid
      sequence comparisons, it has been suggested that mammalian and nonmammalian liver
      FABPs may be paralogous proteins that originated by gene duplication, rather than
      as a consequence of mutations of the same gene. In this paper we report the
      isolation and amino acid sequence determination of two FABPs from axolotl
      (Ambistoma mexicanum) liver. One of them is similar to mammalian liver FABPs (L
      FABPs) and the other to chicken, catfish and iguana liver FABPs (Lb-FABPs). The
      finding of both L-FABP and Lb-FABP in a single species, as reported here,
      indicates that they are paralogous proteins. The time of divergence of these two
      liver FABP types is estimated to be of approximately 694 million years ago. The
      ligand-binding properties of axolotl liver FABPs were studied by means of
      parinaric-acid-binding and parinaric-acid-displacement assays. L-FABP binds two
      fatty acids per molecule but Lb-FABP displays a fatty-acid-conformation-dependent
      binding stoichiometry; L-FABP shows a higher affinity for fatty acids, especially
      oleic acid, while Lb-FABP has a higher affinity for other hydrophobic ligands,
      especially retinoic acid. In addition, the tissue-expression pattern is
      different, L-FABP is present in liver and intestinal mucosa while the expression
      of Lb-FABP is restricted to liver. Data indicate distinct functional properties
      of both liver FABP types.

PMID- 9914486
TI  - Rel transcription factors contribute to elevated urokinase expression in human
      ovarian carcinoma cells.
AB  - Elevated levels of the urokinase-type plasminogen activator (uPA) in tumor cells
      are conductive to tumor cell spread and metastasis. In a previous study we
      observed that suppression of RelA dramatically reduced endogenous uPA synthesis
      in the human ovarian cancer cell line OV-MZ-6. Because the uPA promoter contains
      three potential Rel-like protein binding motifs (RRBE, 5'-NF-kappaB, and 3'-NF
      kappaB) we conducted the first thorough systematic uPA promoter analysis to
      examine the direct impact of Rel proteins on uPA gene transcription. Disruption
      of RRBE resulted in a approximately 40% decrease in uPA promoter activity,
      mutation of the 5'-NF-kappaB motif led to an additional 20% decrease. The 3'-NF
      kappaB motif was not active. Overexpression of RelA significantly enhanced uPA
      promoter activity, whereas IkappaB-alpha overexpression reduced uPA promoter
      activity by 40%. These data were supported by the finding that endogenous uPA was
      also increased sixfold by overexpression of RelA and decreased by 30% upon
      overexpression of IkappaB-alpha. Transfection of OV-MZ-6 cells with antisense
      deoxynucleotides directed to RelA expression reduced uPA promoter activity by at
      least 40%. Our data clearly suggest that by binding to uPA promoter elements, Rel
      transcripton factors contribute directly to elevated uPA gene expression in human
      ovarian cancer cells, thereby promoting the multiple functions of uPA during
      tumor growth and metastasis.

PMID- 9914485
TI  - Characterization and molecular cloning of the lectin from Helianthus tuberosus.
AB  - A lectin called Helianthus tuberosus agglutinin or Heltuba has been isolated from
      tubers of the Jerusalem artichoke, a typical representative of the Asteraceae
      family. Heltuba is a tetrameric protein composed of four identical subunits of
      15.5 kDa and exhibits a preferential specificity towards oligomannosides. Cloning
      of the corresponding cDNAs revealed that the mature lectin polypeptide comprises
      the entire open reading frame of the cDNA suggesting that the primary translation
      product is not processed and that the lectin is a cytosolic protein. Searches in
      the databases revealed sequence similarity with lectins from the taxonomically
      unrelated Convolvulaceae and Moraceae species. Therefore, the discovery of
      Heltuba is of great importance in view of the occurrence and molecular evolution
      of the jacalin-related lectins.

PMID- 9914488
TI  - A new model for microtubule-associated protein (MAP)-induced microtubule
      assembly. The Pro-rich region of MAP4 promotes nucleation of microtubule assembly
      in vitro.
AB  - The microtubule-binding domains of microtubule-associated protein (MAP) 2, tau,
      and MAP4 are divided into three distinctive regions: the Pro-rich region, the AP
      sequence region and the tail region (Aizawa, H., Emori, Y., Murofushi, H.,
      Kawasaki, H., Sakai., H., and Suzuki, K. (1990) J. Biol. Chem. 265, 13849-13855).
      Electron microscopic observation showed that the taxol-stabilized microtubules
      alone and those mixed with the A4T fragment (containing the AP sequence region
      and the tail region) had a long, wavy appearance, while those mixed with the PA4T
      fragment (containing the Pro-rich region, the AP sequence region, and the tail
      region) or the PA4 fragment (containing the Pro-rich region and the AP sequence
      region) were shorter and straighter. Stoichiometries of the binding between the
      fragments and the tubulin dimers were approximately between 1 and 2, suggesting
      that not all of the AP sequences in the AP sequence region bound to tubulin.
      Binding affinity of the PA4T fragment is only four times higher than that of the
      A4T fragment, while the microtubule nucleating activity of the PA4T fragment is
      far greater. Based on these results, we propose that the nucleation of
      microtubule assembly is promoted by the bridging activity of the Pro-rich region
      in the MAPs.

PMID- 9914487
TI  - mRNA stability and selenocysteine insertion sequence efficiency rank
      gastrointestinal glutathione peroxidase high in the hierarchy of selenoproteins.
AB  - The recently described gastrointestinal glutathione peroxidase (GI-GPx) is the
      fourth member of the family of the selenoenzymes glutathione peroxidases (GPx).
      In contrast to the more uniform distribution of, for example, the classical
      glutathione peroxidase (cGPx), it is expressed exclusively in the
      gastrointestinal tract and has, therefore, been suggested to function as a
      primary barrier against alimentary hydroperoxides. In order to get an idea of its
      relative importance we investigated its position in the hierarchy of
      selenoprotein expression. The selenium-dependent expression of GI-GPx was
      analyzed in comparison with that of other GPx types at the level of mRNA and
      protein in HepG2 and CaCo-2 cells. Furthermore, the selenocysteine insertion
      sequence (SECIS) efficiencies of GI-GPx, phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) and cGPx in response to selenium were determined by a reporter
      gene assay in human hepatoma cells and baby hamster kidney cells. GI-GPx mRNA
      levels increased during selenium deficiency, whereas cGPx mRNA levels decreased
      and PHGPx mRNA levels remained almost unaffected. In cells grown in selenium-poor
      media, all GPx-types were low in both activity and immunochemical reactivity.
      Upon selenium repletion immunoreactive GI-GPx protein reached a plateau after 10
      h, whereas cGPx started to be expressed at 24 h and did not reach its maximum
      level before 3 days. SECIS efficiencies decreased in the order PHGPx > cGPx > GI
      GPx. The augmentation of SECIS efficiencies by selenium was highest for cGPx and
      intermediate for PHGPx, whereas it was marginal for GI-GPx. The high mRNA
      stability under selenium restriction, the speed of biosynthesis upon selenium
      repletion and the marginal effect of selenium on the SECIS efficiency indicate
      that of the GPx isotypes, GI-GPx ranks highest in the hierarchy of selenoproteins
      and point to a vital role of GI-GPx in the gastrointestinal tract.

PMID- 9914489
TI  - Selective formation of Gsalpha-MHC I complexes after desensitization of human
      platelets with iloprost.
AB  - Prolonged treatment of human platelets with the adenylate cyclase-stimulating
      prostacyclin analog iloprost leads to reduction in cAMP formation. Previous
      studies have demonstrated that this may be ascribed to modification of both
      receptor and Gsalpha function rather than of the catalytic component of adenylate
      cyclase [Mollner, S., Deppisch, H. & Pfeuffer, T. (1992) Eur. J. Biochem. 210,
      539-544]. Iloprost-induced desensitization was accompanied by the formation of a
      Gsalpha-containing 90-kDa product in membranes treated with the bifunctional
      cross-linker 1,6-bismaleimidohexane. The cAMP-inducing prostanoid PGD2, which
      does not promote desensitization, did not cause formation of the 90-kDa species
      either. The long-term effect of the common G-protein activator [AlF4]- on human
      platelet adenylate cyclase was shown in many respects to be comparable with that
      of iloprost. However, [AlF4]- treatment also failed to induce the 90-kDa species,
      showing that different mechanisms of desensitization were operating. Treatment of
      the cross-linked 90-kDa complex with PNGase F demonstrated the glycoprotein
      nature of the Gsalpha-associated component. The 90-kDa cross-linked product was
      purified by consecutive immunoaffinity chromatography and preparative PAGE to
      apparent homogeneity. Analysis of the purified protein by MS suggested that,
      besides Gsalpha, the heavy chain of MHC I (HLA-A2) was part of the complex. This
      was confirmed by coprecipitation of Gsalpha by the monoclonal anti-(MHC I)
      antibody W6/32.

PMID- 9914490
TI  - Biosynthesis of scarab beetle pheromones.
AB  - Chemical communication in scarab beetles (Coleoptera: Scarabaeidae) is achieved
      with a wide variety of pheromones, but one typical structure is the gamma-lactone
      having a long unsaturated hydrocarbon chain. Several species utilize (R, Z)-5-(-)
      (oct-1-enyl)-oxacyclopentan-2-one (buibuilactone), (R, Z)-5-(-)-(dec-1-enyl)
      oxacyclopentan-2-one and (S, Z)-5-(+)-(dec-1-enyl)-oxacyclopentan-2-one [(R)
      japonilure and (S)-japonilure]. Using deuterated precursors, we have demonstrated
      that these compounds are biosynthesized from fatty acids. (9, 10-d4)-Palmitic
      acid, (9,10-d4)-stearic acid, (9,10-d2)-palmitoleic acid, (9,10-d2)-oleic acid,
      (9,10-d2)-8-hydroxypalmitoleic acid and (9,10-d2)-8-hydroxyoleic acid were
      readily incorporated by female Anomala cuprea into the pheromone molecules, while
      (Z)-(5, 6-d2)-5-dodecenoic acid and (Z)-(5,6-d2)-5-tetradecenoic acid were not.
      Therefore, the reaction pathway starts from saturated fatty acids, involves their
      desaturation, followed by 8-hydroxylation, chain shortening and cyclization. The
      products obtained from racemic (9,10-d2)-8-hydroxypalmitoleic acid and (9,10-d2)
      8-hydroxyoleic acid were also racemic, implying that the steps following
      hydroxylation were not stereospecific. Perdeuterated palmitic acid was applied to
      disclose the mechanism of the unique hydroxylation reaction. Retention of all
      deuterium atoms implied that this reaction was a direct process mediated by a
      specific fatty acid hydroxylase, and preceding desaturation or epoxidation was
      not involved.

PMID- 9914491
TI  - Formation of catalytically active acetyl-S-malonate decarboxylase requires
      malonyl-coenzyme A:acyl carrier protein transacylase as auxiliary enzyme
      [corrected].
AB  - Functional malonate decarboxylase of Klebsiella pneumoniae is an acetyl-S-enzyme
      with an acetylated phosphoribosyl dephospho-CoA prosthetic group. The mdcH gene
      product acts as a malonyl-CoA:ACP transacylase and initiates the activation of
      (deacetyl)malonate decarboxylase by malonyl-transfer to the prosthetic group. The
      malonyl residue is subsequently decarboxylated to an acetyl residue by the
      decarboxylase itself. Purified malonate decarboxylase consists of the four
      subunits MdcA, D, E and C in an apparent 1 : 1 : 1 : 1 stoichiometry. In
      addition, the preparation contains substoichiometric amounts of MdcH comigrating
      on SDS/PAGE with MdcD. Malonate decarboxylase isolated from strains with a
      deletion of the mdcH gene was not activated with malonyl-CoA. Activity could be
      gained, however, in the additional presence of MdcH that has been synthesized in
      Escherichia coli and purified from inclusion bodies. Substrates for MdcH are
      malonyl-CoA or methylmalonyl-CoA but not acetyl-CoA. The enzyme has Km values of
      16 microm for both substrates and Vmax for malonyl-CoA of 190 U.mg-1 and for
      methylmalonyl-CoA of 37 U.mg-1. Transfer of the methylmalonyl-residue to the
      prosthetic group proceeds via the covalent methylmalonyl-MdcH intermediate. The
      transacylase is specifically inhibited by N-ethylmaleimide, and preincubation
      with malonyl-CoA or methylmalonyl-CoA protects the enzyme from this inhibition.

PMID- 9914492
TI  - A new exon in the 5' untranslated region of the connexin32 gene.
AB  - The cloning and sequencing of two bovine connexin32 cDNAs are reported.
      Comparative analysis with known corresponding mammalian cDNA and protein
      sequences, besides confirming a high degree of similarity among these proteins,
      allowed us to identify some specific features of the bovine connexin32 gene. The
      latter include: the presence of a novel exon in the 5' UTR which is alternatively
      spliced, giving rise to a new mRNA species; the presence of two potential hairpin
      loops in the 5' and 3' UTR; and the presence of an additional amino acid,
      glycine235, in the C-terminal domain of the 284 residue protein. Among the common
      features, the presence of polypyrimidine clusters within the 3' UTR, containing a
      consensus sequence for a cis-acting element, is noteworthy. Expression of
      connexin32 mRNAs was analysed in 16 bovine tissues. Transcript analysis suggests
      the presence, in cattle, of an alternative downstream promoter.

PMID- 9914493
TI  - Primary structure of a cadmium-induced metallothionein from the insect Orchesella
      cincta (Collembola).
AB  - The induction of metallothionein was studied in the springtail Orchesella cincta
      (Collembola), a species of insect living in forest soils. Upon dietary exposure
      to Cd, two Cd-binding, cysteine-rich peptides were isolated from whole-body
      homogenates, using gel filtration and reversed-phase FPLC. Mass spectrometric
      analysis revealed that the molecular masses of these peptides were 2989 Da and
      4139 Da, respectively. Amino acid sequencing of the 2989-Da peptide resulted in a
      sequence typical for a metallothionein. Sequencing of the 4139-Da protein was
      unsuccessful, probably due to N-terminal blockage. Using different PCR techniques
      (3' and 5' RACE) with (degenerate) primers based on the identified amino acid
      sequence of the 2989 Da peptide, a metallothionein cDNA was isolated. The
      sequence of this cDNA potentially codes for a protein of 77 amino acids. The 2989
      Da peptide corresponds to the C-terminal part of this protein. The 4139-Da
      protein is probably encoded by the N-terminal part of this protein. These results
      suggest that the identified peptides are products of one gene, and that the
      primary gene product is subject to post-translational processing. The deduced
      amino acid sequence of the O. cincta metallothionein shows low sequence
      similarity with metallothioneins from Drosophila. The similarity between O.
      cincta MT and MTs of invertebrates is not higher than that between O. cincta and
      vertebrates.

PMID- 9914495
TI  - Structure and serological specificity of a new acidic O-specific polysaccharide
      of Proteus vulgaris O45.
AB  - The following structure of the O-specific polysaccharide (OPS) of Proteus
      vulgaris O45 lipopolysaccharide (LPS) was established using 1H- and 13C-NMR
      spectroscopy, including two-dimensional NOESY and H-detected 1H, 13C
      heteronuclear multiple-quantum coherence ( HMQC) experiments: [structure: see
      text text] Immunochemical studies, using rabbit polyclonal anti-P. vulgaris O45
      serum and LPS, OPS and Smith-degraded OPS of P. vulgaris O45, showed the
      importance of beta-D-GlcA in manifesting the serological specificity of the O
      antigen studied.

PMID- 9914494
TI  - Cloning, properties and tissue distribution of natriuretic peptide receptor-A of
      euryhaline eel, Anguilla japonica.
AB  - During the course of cloning and characterization of natriuretic peptide receptor
      A (NPR-A) from the euryhaline fish eel, Anguilla japonica, we identified a splice
      variant with unique structural properties that affect ligand-inducible intrinsic
      guanylate cyclase activity. The variant, generated from a splice between a
      cryptic donor site and the normal acceptor site, lacked nine amino acid residues
      (VFTKTGYYK) in the kinase-like regulatory domain. This deletion of a very short
      segment resulted in the complete loss of the ligand inducibility of the cyclase
      activity. The nine-amino acid segment may therefore be useful as a target for
      studies aimed at clarifying the mechanism of activation of the guanylate cyclase
      domain. Characterization of the normal form of eel NPR-A also led to the
      following interesting findings. Although eel NPR-A had a domain structure very
      similar to that of mammalian counterparts, it lacked the third cysteine residue
      in the extracellular domain which is conserved among mammalian NPR-A molecules.
      The eel receptor bound both amidated and nonamidated eel atrial natriuretic
      peptide (eANP) with high affinity but, when assayed for ligand-inducible cGMP
      generation, it responded efficiently only to physiological concentrations of the
      amidated ligand, suggesting that the biologically active form is the amidated
      eANP, and the nonamidated form acts as a partial antagonist; similarly,
      nonhomologous rat ligands behaved like antagonists toward the eel receptor in the
      concentration range 0.1-10 nm. The receptor message was found to be relatively
      abundant in the osmoregulatory organs such as the gill, kidney, intestine and
      urinary bladder.

PMID- 9914497
TI  - Elapid venom toxins: multiple recruitments of ancient scaffolds.
AB  - Nigroxins A and B, two myotoxic phospholipases A2 (PLA2s) from the venom of the
      American elapid Micrurus nigrocinctus, belong to a new PLA2 subclass. Their
      primary structures were established and compared with those of PLA2s that have
      already been studied with respect to myotoxic activity. The combination of amino
      acid residues Arg15, Ala100, Asn108 and a hydrophobic residue at position 109 is
      present exclusively in class I PLA2s that display myotoxic activity. These
      residues cluster within a surface region rich in positive charges and are
      suggested to play a role in the interaction with the target membrane of the
      muscle fibers. It is concluded that the myotoxic PLA2s resulted from recruitment
      of an ancient scaffold. Dendrotoxins and alpha-neurotoxins are similarly derived
      from other old structures, which are, however, now also present in nontoxic
      proteins that are widely distributed throughout the animal kingdom. The
      evolutionary pathways by which elapid PLA2s acquired myotoxicity and dendrotoxins
      acquired K+-channel blocker activity are traced. They demonstrate how existing
      scaffolds were adapted stepwise to serve toxic functions by exchange of a few
      surface-exposed residues.

PMID- 9914496
TI  - Inhibition of membrane-bound electron transport of the methanogenic archaeon
      Methanosarcina mazei Go1 by diphenyleneiodonium.
AB  - The proton translocating electron transport systems (F420H2:heterodisulfide
      oxidoreductase and H2:heterodisulfide oxidoreductase) of Methanosarcina mazei Go1
      were inhibited by diphenyleneiodonium chloride (DPI) indicated by IC50 values of
      20 nmol DPI.mg-1 protein and 45 nmol DPI.mg-1 protein, respectively. These
      effects are due to a complex interaction of DPI with key enzymes of the electron
      transport chains. It was found that 2-hydroxyphenazine-dependent reactions as
      catalyzed by F420-nonreducing hydrogenase, F420H2 dehydrogenase and
      heterodisulfide reductase were inhibited. Interestingly, the H2-dependent
      methylviologen reduction and the heterodisulfide reduction by reduced
      methylviologen as catalyzed by the hydrogenase and the heterodisulfide reductase
      present in washed membranes were unaffected by DPI, respectively. Analysis of the
      redox behavior of membrane-bound cytochromes indicated that DPI inhibited CoB-S-S
      CoM-dependent oxidation of reduced cytochromes and H2-dependent cytochrome
      reduction. Membrane-bound and purified F420H2 dehydrogenase were inhibited by DPI
      irrespectively whether methylviologen + metronidazole or 2-hydroxyphenazine were
      used as electron acceptors. Detailed examination of 2-hydroxy-phenazine-dependent
      F420H2-oxidation revealed that DPI is a competitive inhibitor of the enzyme,
      indicated by the Km value for 2-hydroxyphenazine, which increased from 35 microm
      to 100 microm in the presence of DPI. As DPI and phenazines are structurally
      similar with respect to their planar configuration we assume that the inhibitor
      is able to bind to positions where interaction between phenazines and components
      of the electron transport systems take place. Thus, electron transfer from
      reduced 2-hydroxyphenazine to cytochrome b2 as part of the heterodisulfide
      reductase and from H2 to cytochrome b1 as subunit of the membrane-bound
      hydrogenase is affected in the presence of DPI. In case of the F420H2
      dehydrogenase electron transport from FAD or from FeS centers to 2
      hydroxyphenazine is inhibited.

PMID- 9914498
TI  - Desulfovibrio gigas neelaredoxin. A novel superoxide dismutase integrated in a
      putative oxygen sensory operon of an anaerobe.
AB  - Neelaredoxin, a small non-heme blue iron protein from the sulfate-reducing
      bacterium Desulfovibrio gigas [Chen, L., Sharma, P., LeGall, J., Mariano, A.M.,
      Teixeira M. and Xavier, A.V. (1994) Eur. J. Biochem. 226, 613-618] is shown to be
      encoded by a polycistronic unit which contains two additional open reading frames
      (ORF-1 and ORF-2) coding for chemotaxis-like proteins. ORF-1 has domains highly
      homologous with those structurally and functionally important in methyl-accepting
      chemotaxis proteins, including two putative transmembrane helices, potential
      methylation sites and the interaction domain with CheW proteins. Interestingly,
      ORF-2 encodes a protein having homologies with CheW proteins. Neelaredoxin is
      also shown to have significant superoxide dismutase activity (1200 U. mg-1),
      making it a novel type of iron superoxide dismutase. Analysis of genomic data
      shows that neelaredoxin-like putative polypeptides are present in strict
      anaerobic archaea, suggesting that this is a primordial superoxide dismutase. The
      three proteins encoded in this operon may be involved in the oxygen-sensing
      mechanisms of this anaerobic bacterium, indicating a possible transcriptional
      mechanism to sense and respond to potential stress agents.

PMID- 9914499
TI  - Analysis of a conditional degradation signal in yeast and mammalian cells.
AB  - The N-end rule pathway is a ubiquitin-dependent proteolytic system, the targets
      of which include proteins that bear destabilizing N-terminal residues. The latter
      are a part of the degradation signal called the N-degron. Arg-DHFRts, an
      engineered N-end rule substrate, bears N-terminal arginine (a destabilizing
      residue) and DHFRts [a temperature-sensitive mouse dihydrofolate reductase (DHFR)
      moiety]. Previous work has shown that Arg-DHFRts is long-lived at 23 degreesC but
      short-lived at 37 degreesC in the yeast Saccharomyces cerevisiae. In the present
      work, we extended this analysis, and found that the degradation of Arg-DHFRts can
      be nearly completely inhibited in vivo by methotrexate (MTX), a low-Mr ligand of
      DHFR. In S. cerevisiae, Arg-DHFRts is degraded at 37 degreesC exclusively by the
      N-end rule pathway, whereas in mouse cells the same protein at the same
      temperature is also targeted by another proteolytic system, through a degron in
      the conformationally perturbed DHFRts moiety. In mouse cells, MTX completely
      inhibits the degradation of Arg-DHFRts through its degron within the DHFRts
      moiety, but only partially inhibits degradation through the N-degron. When the N
      terminus of Arg-DHFRts was extended with a 42-residue lysine-lacking extension,
      termed eDeltaK, the resulting Arg-eDeltaK-DHFRts was rapidly degraded at both 23
      degreesC and 37 degreesC. Moreover, the degradation of Arg-eDeltaK-DHFRts, in
      contrast with that of Arg-DHFRts, could not be inhibited by MTX, suggesting that
      the metabolic stability of Arg-DHFRts at 23 degreesC results, at least in part,
      from steric inaccessibility of its N-terminal arginine. The N-degron of Arg
      DHFRts is the first example of a portable degradation signal the activity of
      which can be modulated in vivo by a cell-penetrating compound. We discuss
      implications of this advance and the mechanics of targeting by the ubiquitin
      system.

PMID- 9914500
TI  - All three IkappaB isoforms and most Rel family members are stably associated with
      the IkappaB kinase 1/2 complex.
AB  - Nuclear factor kappa B (NF-kappaB) is an important transcription factor for the
      genes of many pro-inflammatory proteins and is strongly activated by the
      cytokines interleukin-1 and tumor necrosis factor (TNF)alpha under various
      pathological conditions. In nonstimulated cells, NF-kappaB is present in the
      cytosol where it is complexed to its inhibitor IkappaB. Activation of NF-kappaB
      depends on the signal-induced phosphorylation of IkappaB by specific IkappaB
      kinases which initiates the inhibitor's conjugation to ubiquitin and subsequent
      degradation by the proteasome. We used both TNF-stimulated and okadaic-acid
      stimulated HeLa cells to purify three biochemically distinct kinase activities
      targeting one or both of the two serines (S32 and S36) in IkappaBalpha which
      induce its rapid degradation upon cytokine stimulation. All three activities
      correspond to known IkappaB kinases: the mitogen-activated 90 kDa ribosomal S6
      kinase (p90rsk1), the IkappaB kinase 1/2 complex (IKK1/2) and casein kinase II
      (CK II). However, we found that only one of the activities, namely the IKK1/2
      complex, exists as a pre-assembled kinase-substrate complex in which the IKKs are
      directly or indirectly associated with several NF-kappaB-related and IkappaB
      related proteins: RelA, RelB, cRel, p100, p105, Ikappa Balpha, Ikappa Bbeta and
      Ikappa Bepsilon. The existence of stable kinase-substrate complexes, the presence
      of all three known IkappaB isoforms in these complexes and our observation that
      the IKK complex is capable of phosphorylating Ikappa Balpha-, Ikappa Bbeta- and
      Ikappa Bepsilon-derived peptides at the respective degradation-relevant serines
      suggests that the IKK complex exerts a broad regulatory role for the activation
      of different NF-kappaB species. In contrast to previous studies, which locate CK
      II phosphorylation sites exclusively to the C-terminal PEST sequence of Ikappa
      Balpha, we observed efficient phosphorylation of serine 32 in Ikappa Balpha by
      the purified endogenous CK II complex. Therefore, both p90rsk1 and CK II have the
      same preference for phosphorylating only one of the two serines which are
      relevant for inducible degradation.

PMID- 9914501
TI  - Enzyme level of enterococcal F1Fo-ATPase is regulated by pH at the step of
      assembly.
AB  - The amount of F1Fo-ATPase in Enterococcus hirae (formerly Streptococcus faecalis)
      increases when the cytoplasmic pH is lowered below 7.6, and protons are extruded
      to maintain the cytoplasmic pH at around 7.6. In the present study, we found that
      the transcriptional activity of the F1Fo-ATPase operon was not regulated by pH.
      The synthesis of F1 subunits was increased 1.65 +/- 0.12-fold by the
      acidification of medium from pH 8.0 to pH 5.3. Western-blot analysis showed that
      there were F1 subunits in the cytoplasm, and the number of alpha plus beta
      subunits in the cytoplasm was 50% of the total number of the subunits in cells
      growing at pH 8.0. This decreased to 22% after shifting the medium pH to 5.3,
      with a concomitant 5.1-fold increase in the level of membrane-bound F1Fo-ATPase.
      The cytoplasmic F1 subunits were shown to be degraded, and Fo subunits not
      assembled into the intact F1Fo complex were suggested to be digested. These data
      suggest that regulation of the enzyme level of F1Fo-ATPase by the intracellular
      pH takes place mainly at the step of enzyme assembly from its subunits.

PMID- 9914502
TI  - Structural changes of horseradish peroxidase in presence of low concentrations of
      urea.
AB  - The presence of very low concentrations of the widely used denaturant urea
      induces structural changes in the monomeric heme-containing enzyme, horseradish
      peroxidase (HRP). Structural alterations in the protein were reflected in
      quenching studies of tryptophan fluorescence using the widely used quencher
      acrylamide. Stern-Volmer quenching constants measured in presence of urea, even
      in concentrations below 100 mm, were higher than those measured in absence of the
      denaturant. The fluorescence emission maximum of 1, 8-ANS, used as a probe for
      monitoring conformational changes in the enzyme, was blue-shifted from 530 nm in
      aqueous buffer to 518 nm when incorporated in native HRP. This blue shift
      increased further by 3 nm in presence of HRP preincubated with 100 mm urea,
      whereupon it steadily decreased with increasing urea concentration to become zero
      at 8 m urea. The mean fluorescence lifetime of 1,8-ANS incorporated in HRP was
      much higher than that of ANS in aqueous buffer, and showed continuous variation
      with the concentration of urea in which the enzyme was incubated. Systematic
      changes in the microenvironment of the heme moiety in HRP were also reflected in
      the visible CD spectra of the enzyme incubated with low concentrations of urea.
      These results are consistent with those of our earlier studies performed with the
      denaturant guanidinium chloride and indicate structural relaxation of HRP, with
      retention of enzymatic activity and native-like secondary structure, in presence
      of millimolar concentrations of urea.

PMID- 9914503
TI  - Discrimination of cruzipain, the major cysteine proteinase of Trypanosoma cruzi,
      and mammalian cathepsins B and L, by a pH-inducible fluorogenic substrate of
      trypanosomal cysteine proteinases.
AB  - The substrate specificity of cruzipain, the major cysteine proteinase of
      Trypanosoma cruzi, was investigated using a series of dansyl-peptides based on
      the putative autoproteolytic sequence of the proteinase (VVG-GP) located at the
      hinge region between the catalytic domain and the C-terminal extension. Replacing
      Val with Pro at P2 in this sequence greatly improved the rate of cleavage by
      cruzipain. Tyr and Val residues are preferred at P3 by all cysteine proteinases
      whatever their origin, whereas only cruzipain and cathepsin L cleaved substrate
      with a His at that position. The combination of a Pro at P2 and His at P3
      abolished cleavage by cathepsin L, so that only cruzipain was able to cleave the
      HPGGP peptide at the GG bond. A substrate with intramolecularly quenched
      fluorescence was raised on this sequence (Abz-HPGGPQ-EDDnp) which was also
      specifically cleaved by cruzipain (kcat/Km of 157 000 m-1. s-1) and by a
      homologous proteinase from Trypanosoma congolense. The pH activity profile of
      cruzipain on Abz-HPGGPQ-EDDnp showed a narrow peak with a maximum at pH 5.5 and
      no cleavage above pH 6.8, although trypanosomal cysteine proteinases remain
      active at basic pH. The lack of activity at neutral and basic pH was due to a
      decrease in kcat, while the Km remained essentially unchanged, demonstrating that
      the substrate still binds to the enzyme and therefore behaves as an inhibitor.
      Changing the substrate into an inhibitor depended on the deprotonation of the His
      residue in the substrate, as deduced from a comparison of the pH activity profile
      with that of a related, but uncharged, substrate. Abz-HPGGPQ-EDDnp also inhibited
      mammalian cathepsins B and L but was not cleaved by these proteinases at any pH.
      The importance of the His residue at P3 for cleavage by cruzipain was confirmed
      by substituting Lys for His at that position. The resulting peptide was not
      cleaved by cruzipain in spite of the presence of a positively charged group at
      P3, but still interacted with the enzyme. It was concluded that the presence of
      an imidazolium group at P3 was essential to endow the HPGGPQ sequence with the
      properties of a cruzipain substrate.

PMID- 9914504
TI  - I-NjaI, a nuclear intron-encoded homing endonuclease from Naegleria, generates a
      pentanucleotide 3' cleavage-overhang within a 19 base-pair partially symmetric
      DNA recognition site.
AB  - Different species of the amoebo-flagellate Naegleria harbor optional group I
      introns in the nuclear ribosomal DNA that contain open reading frames. Intron
      proteins from Naegleria jamiesoni, Naegleria andersoni, and Naegleria italica
      (named I-NjaI, I-NanI and I-NitI, respectively) were expressed in Escherichia
      coli and found to be isoschizomeric homing endonucleases that specifically
      recognize and cleave intron-lacking homologous alleles of ribosomal DNA. The I
      NjaI endonuclease was affinity purified, characterized in more detail, and found
      to generate five-nucleotide 3' staggered ends at the intron insertion site which
      differs from the ends generated by all other known homing endonucleases. The
      recognition site was delimited and found to cover an approximately 19 base-pair
      partially symmetric sequence spanning both the cleavage site and the intron
      insertion site. The palindromic feature was supported by mutational analysis of
      the target DNA. All single-site substitutions within the recognition sequence
      were cleaved by the purified I-NjaI endonuclease, but at different efficiencies.
      The center of symmetry and cleavage was found to be completely degenerate in
      specificity, which resembles that of the subclass IIW bacterial restriction
      enzymes.

PMID- 9914505
TI  - Mouse Rt6.1 is a thiol-dependent arginine-specific ADP-ribosyltransferase.
AB  - Mouse T-cell antigens Rt6.1 and Rt6.2 are glycosylphosphatidylinositol-anchored
      arginine-specific adenosine diphosphate (ADP)-ribosyltransferases. In the present
      study, we obtained evidence that an arginine-specific ADP-ribosyltransferase
      activity liberated from BALB/c mouse splenocytes by phosphatidylinositol-specific
      phospholipase C increased fivefold in the presence of dithiothreitol and that the
      activity was immunoprecipitated by polyclonal antibodies generated against
      recombinant rat RT6.1. When mouse Rt6.1 was expressed as a recombinant protein,
      the transferase activity of Rt6.1 was stimulated by dithiothreitol, and inhibited
      by N-ethylmaleimide, while activities of recombinant mouse Rt6.2 and the Glu-207
      mutant of rat RT6.1 [Hara, N., Tsuchiya, M., and Shimoyama, M. (1996) J. Biol.
      Chem. 271, 29552-29555] were unaffected by either agent. In addition to four
      cysteine residues conserved among mouse Rt6 and rat RT6 antigens, Rt6.1 has two
      extra cysteine residues at positions 80 and 201. To investigate a contribution of
      these extra cysteines in mouse Rt6.1 to thiol dependency of Rt6.1 transferase
      activity, Cys-80 and Cys-201 of Rt6.1 were replaced with serine and
      phenylalanine, respectively, the corresponding residues of mouse Rt6. 2 and rat
      RT6.1. Transferase activity of the Phe-201 mutant of Rt6.1 lost thiol dependency
      while that of the Ser-80 mutant remained thiol-dependent. Thus, we conclude that
      mouse Rt6.1 is a thiol-dependent arginine-specific ADP-ribosyltransferase, and
      that Cys-201 confers thiol dependency on Rt6.1 transferase. Our study indicates
      that arginine-specific ADP-ribosyltransferase activity detected on BALB/c mouse
      splenocytes is attributed to Rt6.1 and that Rt6.1 differs from Rt6.2 in enzymatic
      property of the transferase and perhaps in immunoregulatory functions.

PMID- 9914506
TI  - Crystal state and solution conformation of the B blood group trisaccharide alpha
      L-Fucp-(1-->2)-[alpha-D-Galp]-(1-->3)]-beta-D-Galp-OCH3.
AB  - The crystal structure of the human B blood group related trisaccharide alpha-L
      Fucp-(1-->2)-[alpha-D-Galp]-(1-->3)-beta-D-Galp-OCH3 (1) has been determined. The
      solution structure of 1 was studied by two-dimensional NMR techniques at 600 MHz
      in D2O solution and the conformational properties were analyzed in terms of the
      torsional angles phiH and psiH, derived from 3JCH coupling constants, and 10
      inter-residue proton-proton distances. 3JCH could be accurately measured by a
      recently introduced two-dimensional heteronuclear correlation experiment
      (EXSIDE). The nuclear Overhauser enhancement-derived distances and the calculated
      torsion angles were compared with the same information available from the crystal
      structure. The agreement is excellent, indicating that the trisaccharide adopts a
      restricted conformation in solution, which was also predicted by the Hard Sphere
      Exo-Anomeric forcefield. The data of 1 are complemented by NMR studies of the
      closely related alpha-L-Fucp-(1-->2)-[6-deoxy-alpha-D-Galp]-(1-->3)-beta-D-Galp O
      (CH2 )7CH3 trisaccharide (2).

PMID- 9914507
TI  - Preferential activation of iron regulatory protein-2 in cell lines as a result of
      higher sensitivity to iron.
AB  - Iron regulatory proteins (IRP)-1 and 2 are cytoplasmic mRNA-binding proteins that
      control intracellular iron homeostasis by regulating the translation of ferritin
      mRNA and stability of transferrin receptor mRNA in an iron-dependent fashion.
      Although structurally and functionally similar, the two IRP are different in
      their mode of regulation, pattern of tissue expression and modulation by multiple
      factors, such as bioradicals. In the present study RNA bandshift assays
      demonstrated that IRP-2, but not IRP-1, activity was higher in cultured cells
      than in tissues. Increased expression of IRP-2 in cell lines was not related to
      immortalization and differentiation but seemed associated to cell proliferation,
      although not closely dependent on cell growth rate. As a growing cell consumes
      more iron than its quiescent counterpart, we assessed the iron status of cell
      lines and found that ferritin content was lower than in tissues. Analysis of IRP
      activity in cell lines supplemented with heme or non-heme iron and in livers of
      iron-loaded and iron-deficient rats indicated that IRP-2 responds more promptly
      than IRP-1 to modulations of iron content. We propose that enhanced IRP-2
      activity in cultured cells could be due to a proliferation-dependent, relative
      iron deficiency that is sensed first by IRP-2.

PMID- 9914508
TI  - Physicochemical and immunological studies of the N-terminal domain of the Torpedo
      acetylcholine receptor alpha-subunit expressed in Escherichia coli.
AB  - The nicotinic acetylcholine receptor (AChR) from the electric organ of Torpedo
      species is an oligomeric protein composed of alpha2 beta gamma delta subunits.
      Although much is known about its tertiary and quaternary structure, the
      conformation of the large extracellular domains of each of the subunits has not
      been analysed in detail. In order to obtain information about the spatial
      structure of the extracellular domain, we have expressed the N-terminal fragment
      1-209 of the Torpedo californica AChR alpha-subunit in Escherichia coli. Two
      vectors coding for a (His)6 tag, either preceding or following the 1-209
      sequence, were used and the recombinant proteins obtained (designated alpha1
      209pET and alpha1-209pQE, respectively) were purified by affinity chromatography
      on a Ni2+-agarose column. The chemical structure of both proteins was verified by
      Edman degradation and mass spectrometry. The proteins were soluble in aqueous
      buffers but to make possible a comparison with the whole AChR or its isolated
      subunits, the recombinant proteins were analyzed both in aqueous solution and
      with the addition of detergents. The two proteins bound [125I]alpha-bungarotoxin
      with equal potency (KD approximately 130 nm, Bmax approximately 10 nmol.mg-1).
      Both were shown to interact with several monoclonal antibodies raised against
      purified Torpedo AChR. The circular dichroism (CD) spectra of the two proteins in
      aqueous solution revealed predominantly beta-structure (50-56%), the fraction of
      alpha-helices amounting to 32-35%. Nonionic (beta-octylglucoside) and
      zwitterionic (CHAPS) detergents did not appreciably change the CD spectra, while
      the addition of SDS or trifluoroethanol decreased the percentage of beta
      structure or increased the alpha-helicity, respectively. The predominance of beta
      structure is in accord with recent data on the N-terminal domain of the mouse
      muscle AChR alpha-subunit expressed in the mammalian cells [West et al. (1997) J.
      Biol. Chem. 272, 25 468]. Thus, expression in E. coli provides milligram amounts
      of the protein that retains several structural characteristics of the N-terminal
      domain of the Torpedo AChR alpha-subunit and appears to share with the latter a
      similar secondary structure. The expression of recombinant polypeptides
      representing functional domains of the AChR provides an essential first step
      towards a more detailed structural analysis.

PMID- 9914509
TI  - Investigation of the structure of spinach photosystem II reaction center complex.
AB  - The photosystem II (PSII) reaction center (RC) complex was isolated from spinach
      and characterized by gel electrophoresis, gel filtration and analytical
      ultracentrifugation. The purified complex contained the PsbA, PsbD, PsbE, PsbF
      and PsbI subunits. Gel filtration and analytical ultracentrifugation indicated
      the presence of a homogeneous complex. The mass of the RC complexes was found to
      be 107 kDa by analytical ultracentrifugation and 132 kDa by scanning transmission
      electron microscopy (STEM). The mass obtained showed the isolated complex to
      exist as a monomer and only one cytochrome b559 (cyt b559) to be associated with
      the RC complex. Digital images of negatively stained RC complexes were recorded
      by STEM and analyzed by single-particle averaging. The complex was 9 nm long and
      5 nm wide, and exhibited a pronounced quasi-twofold symmetry. This supports the
      symmetric organization of the PSII complex, with the PsbA and the PsbD proteins
      in the center and symmetrically arranged PsbB and PsbC proteins at the periphery
      of the monomeric complex.

PMID- 9914511
TI  - Novel glycoinositolphosphosphingolipids, basidiolipids, from Agaricus.
AB  - From the edible mushroom, the basidiomycetes Agaricus bisporus and Agaricus
      campestris, a novel carbohydrate-homologous series of four glyco-inositol-phospho
      sphingolipids, designated basidiolipids, was isolated and the constituents
      purified. The chemical structures of the basidiolipids were elucidated to be:
      Manpbeta1-2inositol1-phospho-ceramide, Galpalpha-6[Fucpalpha-2]Galpbeta-6Manpbeta
      2i nositol1-phospho-ceramide, Galpalpha-6Galpalpha-6[Fucpalpha-2]Galpbeta-
      6Manpbeta-2inositol1-phospho-ceramide and Galpalpha-6Galpalpha-6Galpalpha
      6[Fucpalpha-2] Galpbeta-6Manpbeta-2ino sitol1-phospho-ceramide. All four
      glycolipids contained a ceramide which was composed of phytosphingosine and
      predominantly alpha-hydroxy-behenic and alpha-hydroxy-lignoceric acid.

PMID- 9914510
TI  - The DNA helicases acting in nucleotide excision repair, XPD, CSB and XPB, are not
      required for PCNA-dependent repair of abasic sites.
AB  - DNA repair of abasic sites is accomplished in mammalian cells by two distinct
      base excision repair (BER) pathways: a single nucleotide insertion pathway and a
      proliferating cell nuclear antigen (PCNA)-dependent pathway involving a
      resynthesis patch of 2-10 nucleotides 3' to the lesion. The latter pathway shares
      some enzymatic components with the nucleotide excision repair (NER) pathway
      acting on damage induced by ultraviolet light: both pathways are strictly
      dependent on PCNA and several observations suggest that the polymerization and
      ligation phases may be carried out by common enzymatic activities (DNA polymerase
      delta/epsilon and DNA ligase I). Furthermore, it has been postulated that the
      transcription-NER coupling factor Cockayne syndrome B has a role in BER. We have
      investigated whether three NER proteins endowed with DNA helicase activities (the
      xeroderma pigmentosum D and B gene products and the Cockayne syndrome B gene
      product) may also be involved in repair of natural abasic sites, by using the
      Chinese hamster ovary mutant cell lines UV5, UV61 and 27-1. No defect of either
      the PCNA-dependent or the single nucleotide insertion pathways could be observed
      in UV5, UV61 or 27-1 mutant cell extracts, thus showing that the partial
      enzymatic overlap between PCNA-dependent BER and NER does not extend to DNA
      helicase activities.

PMID- 9914512
TI  - Affinity chromatography using trypanocidal arsenical drugs identifies a specific
      interaction between glycerol-3-phosphate dehydrogenase from Trypanosoma brucei
      and Cymelarsan.
AB  - A 36-kDa protein was isolated by affinity chromatography using Cymelarsan, an
      arsenical drug currently used in African trypanosomiasis treatment, as ligand.
      This protein was identified as glycerol-3-phosphate dehydrogenase. Trypanosomal
      glycerol-3-phosphate was bound covalently, whereas its counterpart from rabbit
      muscle bound by ionic interaction. Arsenical drugs inhibit the enzyme in a dose
      dependent manner. Oxidation of cysteine residues protects against inactivation
      without significantly diminishing enzymic activity. Drug concentrations giving
      50% inhibition of the dehydrogenase activity were determined for the enzyme from
      both Trypanosoma brucei and rabbit and indicate a higher sensitivity of the
      trypanosomal enzyme to arsenical drugs and thiol reagents. MS was used to
      identify residues of glycerol-3-phosphate dehydrogenase bound by Cymelarsan; they
      are not conserved in the mammalian enzyme.

PMID- 9914513
TI  - ATP hydrolysis induces an intermediate conformational state in GroEL.
AB  - The conformational properties of the molecular chaperone GroEL in the presence of
      ATP, its non-hydrolyzable analog 5'-adenylimidodiphosphate (AMP-PNP), and ADP
      have been analyzed by differential scanning calorimetry (DSC), Fourier-transform
      infra-red (FT-IR) and fluorescence spectroscopy. Nucleotide binding to one ring
      promotes a decrease in the Tm value of the GroEL thermal transition that is
      reversed when both rings are filled with nucleotide, indicating that the
      sequential occupation of the two protein rings by these nucleotides has different
      effects on the GroEL thermal denaturation process. In addition, ATP induces a
      conformational change in GroEL characterized by (a) the appearance of a
      reversible low temperature endotherm in the DSC profiles of the protein, and (b)
      an enhanced binding of the hydrophobic probe 8-anilino-naphthalene-1-sulfonate
      (ANS), which strictly depends on ATP hydrolysis. The similar sensitivity to K+ of
      the temperature range where activation of the GroEL ATPase activity, the low
      temperature endotherm, and the increase of the ANS fluorescence are abserved
      strongly indicates the existence of a conformational state of GroEL during ATP
      hydrolysis, different from that generated on ADP or AMP-PNP binding. To achieve
      this intermediate conformation, GroEL mainly modifies its tertiary and quaternary
      structures, leading to an increased exposure of hydrophobic surfaces, with minor
      rearrangements of its secondary structure.

PMID- 9914514
TI  - Stepwise building of a 115-kDa macromolecular edifice monitored by electrospray
      mass spectrometry. The case of acetohydroxy acid isomeroreductase.
AB  - The macromolecular complexes formed by the enzyme acetohydroxy acid
      isomeroreductase with NADPH, magnesium ions and the competitive inhibitor N
      hydroxy-N-isopropyloxamate (IpOHA) were analysed by electrospray mass
      spectrometry. Each ligand was added successively to a protein solution, allowing
      the stoichiometry of the whole macromolecular edifice (115 583 Da) to be
      unambiguously determined. The combination of an electrospray ion source with the
      high mass range magnetic instrument used in the present studies proved to be a
      very powerful tool for characterizing, in a specific manner, the quaternary
      structures of proteins by single mass measurements.

PMID- 9914515
TI  - A comparative study on the structure and function of a cytolytic alpha-helical
      peptide and its antimicrobial beta-sheet diastereomer.
AB  - Antimicrobial peptides which adopt mainly or only beta-sheet structures have two
      or more disulfide bonds stabilizing their structure. The disruption of the
      disulfide bonds results in most cases in a large decrease in their antimicrobial
      activity. In the present study we examined the effect of d-amino acids
      incorporation on the structure and function of a cytolytic alpha-helical peptide
      which acts on erythrocytes and bacteria. The influence of a single or double d
      amino acid replacement in alpha-helical peptides on their structure was reported
      previously in 50% 2,2,2, trifluoroethanol/water [Krause et al. (1995) Anal. Chem.
      67, 252-258]. Here we used Attenuated Total Reflectance Fourier-Transform
      Infrared (ATR-FTIR) spectroscopy and found that the predominant structure of the
      wild-type peptide is alpha-helix in phospholipid membranes, whereas the structure
      of the diastereomer is beta-sheet. However, the linear, beta-sheet diastereomer
      preserved its cytolytic activity on bacteria but not on erythrocytes. Previous
      studies have shown that the ability of antimicrobial peptides to lyse bacteria
      but not normal mammalian cells correlated with their ability to disintegrate
      preferentially negatively charged, but not zwitterionic phospholipid membranes.
      In contrast, the diastereomer described here disrupts zwitterionic and negatively
      charged vesicles with similar potencies to those of the hemolytic wild-type
      peptide. Interestingly, whereas addition of a positive charge to the N-terminus
      of the wild-type peptide (which caused a minor effect on its structure) increased
      activity only towards some of the bacteria tested, similar modification in the
      diastereomer increased activity towards all of them. Furthermore, the modified
      wild-type peptide preserved its potency to destabilize zwitterionic and
      negatively charged vesicles, whereas the modified diastereomer had a reduced
      potency on zwitterionic vesicles but increased potency on negatively charged
      vesicles. Overall our results suggest that this new class of antimicrobial
      diastereomeric peptides bind to the membrane in 'carpet-like' manner followed by
      membrane disruption and breakdown, rather than forming a transmembrane pore which
      interfere with the bacteria potential. These studies also open a way to design
      new broad-spectrum antibacterial peptides.

PMID- 9914516
TI  - Requirement for cAMP-response element (CRE) binding protein/CRE modulator
      transcription factors in thyrotropin-induced proliferation of dog thyroid cells
      in primary culture.
AB  - In several cell types, mostly of epithelial origin, activation of the cAMP
      pathway triggers DNA synthesis and cell division. Regulation of gene expression
      by cAMP involves phosphorylation by pyruvate kinase A and activation of cAMP
      response element binding protein (CREB)/CRE modulator (CREM) transcription
      factors which bind DNA to CRE sites. On the other hand, several CREM isoforms are
      transcriptional repressors, such as the inducible cAMP early repressor (ICER)
      transcription factors, which are synthesized from an intronic promoter of the
      CREM gene. This study investigated the potential role of CREB/CREM transcription
      factors in the cAMP mitogenic pathway, using an experimental model of epithelial
      cells in primary culture, i.e. dog thyroid cells stimulated by thyroid
      stimulating hormone (TSH). In response to TSH, CREB/CREM transcription factors
      were phosphorylated on the serine residue of the pyruvate kinase A consensus
      site. In addition, the synthesis of ICER mRNAs was strongly induced by TSH. This
      transient upregulation of ICER expression correlated with increased protein
      levels. It was restricted to the cAMP pathway, as neither epidermal growth factor
      nor phorbol myristate acetate, which are potent mitogens for dog thyroid cells,
      induced ICER expression. On the other hand, increased expression of ICER mRNAs
      was not detected in dog thyroids chronically stimulated by TSH in vivo. The
      requirement for CREB/CREM transcription factors in the mitogenic effect of TSH
      was assessed by transfecting expression vectors encoding CREM repressors into dog
      thyrocytes in order to interfere with CRE-mediated gene transcription. The
      ectopic expression of ICER Igamma or CREM alpha isoforms inhibited DNA
      replication in dog thyrocytes stimulated by TSH. This inhibitory effect was
      dependent on the ability of CREM repressors to form dimers but did not involve
      their DNA-binding capacity. Together these results show that CREB/CREM
      transcription factors are tightly regulated, at the transcriptional and post
      translational levels, by TSH in dog thyroid cells, and provide clear evidence
      that their activity is required for the cAMP-dependent proliferation of cells in
      primary culture. Moreover, the transient induction of ICER transcription factors
      during mitogenic stimulation by TSH raises questions about the role of these
      potent repressors of CRE-dependent transcription as timers of cellular
      proliferation.

PMID- 9914517
TI  - Oligomerization of the 17-kDa peptide-binding domain of the molecular chaperone
      HSC70.
AB  - Crystallographic and biochemical studies have indicated that the peptide-binding
      site of the molecular chaperone HSC70 is located in a small subdomain comprising
      a beta-sheet motif followed by a helical region, and there is some evidence of
      the involvement of this site in oligomerization of the protein. To determine the
      structure of this subdomain in solution and examine its involvement in
      oligomerization of HSC70, a 17-kDa protein (residues 385-540 of HSC70) consisting
      mainly of the peptide-binding site was constructed and analyzed for
      oligomerization properties. This small domain was found to bind peptides and to
      form oligomers in solution, probably tetramers, which dissociated into monomers
      on peptide binding in a manner comparable with that observed for the whole
      protein. Furthermore, in the 60-kDa fragment of HSC70, which is composed of the
      17-kDa domain and the 44-kDa ATPase domain, not only were the oligomerization
      properties conserved, but dissociation of multimeric species into monomers on ATP
      binding also occurred and peptide stimulation of ATPase activity was restored.
      These results indicate that the isolated 17-kDa peptide-binding domain is
      necessary and sufficient for oligomerization of the whole protein, suggesting
      that the peptide-binding site may be involved in the oligomerization process.

PMID- 9914518
TI  - Synergism between a half-site and an imperfect estrogen-responsive element, and
      cooperation with COUP-TFI are required for estrogen receptor (ER) to achieve a
      maximal estrogen-stimulation of rainbow trout ER gene.
AB  - In all oviparous, liver represents one of the main E2-target tissues where
      estrogen receptor (ER) constitutes the key mediator of estrogen action. The
      rainbow trout estrogen receptor (rtER) gene expression is markedly up-regulated
      by estrogens and the sequences responsible for this autoregulation have been
      located in a 0.2 kb upstream transcription start site within - 40/- 248 enhancer
      region. Absence of interference with steroid hormone receptors and tissue
      specific factors and a conserved basal transcriptional machinery between yeast
      and higher eukaryotes, make yeast a simple assay system that will enable
      determination of important cis-acting regulatory sequences within rtER gene
      promoter and identification of transcription factors implicated in the regulation
      of this gene. Deletion analysis allowed to show a synergistic effect between an
      imperfect estrogen-responsive element (ERE) and a consensus half-ERE to achieve a
      high hormone-dependent transcriptional activation of the rtER gene promoter in
      the presence of stably expressed rtER. As in mammalian cells, here we observed a
      positive regulation of the rtER gene promoter by the chicken ovalbumin upstream
      promoter-transcription factor I (COUP-TFI) through enhancing autoregulation.
      Using a point mutation COUP-TFI mutant unable to bind DNA demonstrates that
      enhancement of rtER gene autoregulation requires the interaction of COUP-TFI to
      the DNA. Moreover, this enhancement of transcriptional activation by COUP-TFI
      requires specifically the AF-1 transactivation function of ER and can be observed
      in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384. Thus, this paper
      describes the reconstitution of a hormone-responsive transcription unit in yeast
      in which the regulation of rtER gene promoter could be enhanced by the
      participation of cis-elements and/or trans-acting factors, such as ER itself or
      COUP-TF.

PMID- 9914519
TI  - Two Arabidopsis thaliana carotene desaturases, phytoene desaturase and zeta
      carotene desaturase, expressed in Escherichia coli, catalyze a poly-cis pathway
      to yield pro-lycopene.
AB  - We have expressed in Escerichia coli the enzymes geranylgeranyl diphosphate
      synthase and phytoene synthase, from the soil bacterium Erwinia stewartii, and
      the two carotene desaturases phytoene desaturase and carotene zeta-carotene
      desaturase from Arabidopsis thaliana. We show that pro-lycopene (7,9,7',9'-tetra
      cis)-lycopene is the main end product of the plant desaturation pathway in these
      cells. In addition, light is required in this system. Whereas in the dark mainly
      zeta-carotene, the phytoene desaturase product, accumulates, illumination leads
      to activation of this intermediate caused by its photoisomerization. zeta
      Carotene then meets the stereospecific requirements of zeta-carotene desaturase
      and pro-lycopene is formed. In contrast, a strain of E. coli carrying
      geranylgeranyl diphosphate synthase, phytoene desaturase and the bacterial
      carotene desaturase CrtI, which mediates lycopene formation from phytoene, does
      not require light, nor is a poly-cis-lycopene species formed. The
      stereoselectivity of the plant-type desaturation pathway expressed in E. coli is
      the same as previously shown with chromoplast membranes. As the phytoene
      desaturase and zeta-carotene desaturase used originate from a system not capable
      of developing chromoplasts, this indicates that the poly-cis pathway of carotene
      desaturation may have a wider occurrence than initially believed.

PMID- 9914520
TI  - Formation of fatty acid ethyl esters in rat liver microsomes. Evidence for a key
      role for acyl-CoA: ethanol O-acyltransferase.
AB  - Fatty acid ethyl esters have been detected in high concentrations in organs
      commonly damaged by alcohol abuse and are regarded as being important non
      oxidative metabolites of ethanol. The formation of fatty acid ethyl esters
      (FAEEs) has been ascribed to two enzymic activities, acyl-CoA : ethanol O
      acyltransferase (AEAT) and FAEE synthase. In the present study we determined AEAT
      and FAEE synthase activities in isolated rat liver microsomes and further
      characterized the microsomal AEAT activity in more detail. The determined AEAT
      and FAEE synthase activities were found to be similar (about 1.7 nmol.min-1.mg
      1). However, the AEAT activity was increased about sixfold by the addition of 250
      microm bis-(4-nitrophenyl) phosphate (a serine esterase inhibitor) to the
      incubation whereas FAEE synthase activity was completely inhibited. p
      Hydroxymercuribenzoic acid (a cysteine-reacting compound) also stimulated AEAT
      activity (about fourfold) but had no effect on FAEE synthase activity. The
      effects of the inhibitors suggest that the formation of FAEEs by AEAT was
      severely counteracted by enzymic hydrolysis of the substrate (acyl-CoA) and to a
      lesser extent the product by serine esterases. dl-Melinamide, a
      hypocholesterolaemic drug, was found to be a very potent inhibitor of AEAT
      activity with an IC50 value of about 2.5 microm. Furthermore, we compared the
      activities of two purified microsomal carboxylesterases, ES-4 and ES-10, and
      identified ES-4 as the enzyme responsible for hydrolysis of FAEEs. The two
      carboxyesterases were also tested for FAEE synthase activity, but neither had any
      detectable activity. Esterase ES-4 was found to have some AEAT activity, but it
      was low. When measured under optimal conditions without competing hydrolysis the
      capacity of AEAT is thus considerably higher than FAEE synthase and the results
      are consistent with an important role for AEAT in the formation of ethyl esters.
      As the ratio acyl-CoA/non-esterified fatty acids is high under normal conditions,
      AEAT is probably the most important enzyme in fatty acid ethyl ester formation.

PMID- 9914521
TI  - 1-Methyl-4-phenylpyridinium ion (MPP+) selectively inhibits the replication of
      mitochondrial DNA.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine is known to cause Parkinsonism in
      its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+). We have previously
      reported that MPP+ decreases the content of mitochondrial DNA (mtDNA)
      independently of the inhibition of complex I in human cells [Miyako, K., Kai, Y.,
      Irie, T., Takeshige, K., and Kang, D. (1997) J. Biol. Chem. 272, 9605-9608]. Here
      we study the mechanism causing the decrease in mtDNA. MPP+ inhibits the
      incorporation of 5-bromo-2'-deoxyuridine into mtDNA but not into nuclear DNA,
      indicating that MPP+ inhibits the replication of mtDNA but not that of the
      nuclear genome. The replication of mtDNA is initiated by the synthesis of the
      heavy strand switched from the transcription of the light strand. MPP+ decreases
      the nascent heavy strands per mtDNA and increases the transcript of the ND6 gene,
      encoded on light strand, per mtDNA. The amount of mitochondrial transcription
      factor A is not decreased. These data suggest that the transcription is not
      inhibited and therefore the transition from transcription to replication of mtDNA
      is lowered in the MPP+-treated cells. Electron microscopy shows that the number
      of mitochondria is not decreased in the MPP+-treated cells, suggesting that MPP+
      does not affect the overall biogenesis of mitochondria. Thus, MPP+ selectively
      inhibits the replication of mtDNA.

PMID- 9914522
TI  - Characterization of the leukotriene B4 receptor in porcine leukocytes. Separation
      and reconstitution with heterotrimeric GTP-binding proteins.
AB  - Leukotriene B4 (LTB4) is a potent chemoattractant derived from arachidonic acid.
      When cDNAs for LTB4 receptor (BLT) were cloned it was found that they belong to a
      guanine nucleotide-binding regulatory protein (G-protein)-coupled receptor
      superfamily. However, purification of BLT from inflammatory cells and
      reconstitution with various types of G-proteins have not been successful. In the
      present study, BLT from porcine leukocytes was solubilized, separated from
      associated G-proteins by Ricinus communis agglutinin (RCA) 120 chromatography,
      and reconstituted with several endogenous and exogenous G-proteins, in
      combination with the fraction which contained endogenous phospholipids and Gbeta
      gamma. Kinetic studies of LTB4 were performed to determine the association with G
      proteins. A partially purified BLT fraction (retained on an RCA120 column) free
      of G-proteins showed a lower affinity for LTB4 (Kd = 500 nm), but reconstitution
      of the BLT fraction with a G-protein-rich fraction (flow-through of an RCA
      column) increased the affinity for LTB4 10-fold (Kd = 50 nm). The partially
      purified BLT fraction was also reconstituted with exogenous G-proteins such as a
      heterotrimeric Gi2 purified from bovine brain or recombinant alpha subunits of
      Gi1, Gi2, Gi3, and Go expressed in Spodoptera frugiperda-9 cells. These increases
      in LTB4 bindings demonstrate that the BLT of porcine leukocytes can interact with
      pertussis toxin-sensitive G-proteins in vitro. The method is useful for the
      purification and reconstitution of other, as yet unisolated, G-protein-coupled
      receptors.

PMID- 9914523
TI  - High level accumulation of single-chain variable fragments in the cytosol of
      transgenic Petunia hybrida.
AB  - The accumulation of five murine single-chain variable fragments, binding to
      dihydroflavonol 4-reductase, was analyzed in transgenic Petunia hybrida plants.
      The five scFv-encoding sequences were cloned in an optimized plant transformation
      vector for expression in the cytosol under control of the 35S promoter. In a
      transient expression assay we found that the scFv expression levels were
      reproducible and correlated with those in stably transformed petunia. Our results
      show that accumulation in the cytosol strongly depends on the intrinsic
      properties of the scFv fragment. Three of the five scFv fragments accumulated to
      unexpectedly high levels in the cytosol of the primary transformants, but no
      phenotypic effect could be detected. Experimental results indicate that one of
      the scFv fragments accumulated in the cytosol to 1% of the total soluble protein
      as a functional antigen-binding protein in the absence of disulphide bonds. This
      observation supports the idea that certain antibody fragments do not need
      disulphide bonds to be stable and functional. Such scFv scaffolds provide new
      opportunities to design scFv fragments for immunomodulation in the cytosol.

PMID- 9914525
TI  - Domain structure, GTP-hydrolyzing activity and 7S RNA binding of Acidianus
      ambivalens ffh-homologous protein suggest an SRP-like complex in archaea.
AB  - In this study we provide, for the first time, experimental evidence that a
      protein homologous to bacterial Ffh is part of an SRP-like ribonucleoprotein
      complex in hyperthermophilic archaea. The gene encoding the Ffh homologue in the
      hyperthermophilic archaeote Acidianus ambivalens has been cloned and sequenced.
      Recombinant Ffh protein was expressed in E. coli and subjected to biochemical and
      functional studies. A. ambivalens Ffh encodes a 50.4-kDa protein that is
      structured by three distinct regions: the N-terminal hydrophilic N-region (N),
      the GTP/GDP-binding domain (G) and a C-terminal located C-domain (C). The A.
      ambivalens Ffh sequence shares 44-46% sequence similarity with Ffh of
      methanogenic archaea, 34-36% similarity with eukaryal SRP54 and 30-34% similarity
      with bacterial Ffh. A polyclonal antiserum raised against the first two domains
      of A. ambivalens Ffh reacts specifically with a single protein (apparent
      molecular mass: 46 kDa, termed p46) present in cytosolic and in plasmamembrane
      cell fractions of A. ambivalens. Recombinant Ffh has a melting point of tm = 89
      degreesC. Its intrinsic GTPase activity obviously depends on neutral pH and low
      ionic strength with a preference for chloride and acetate salts. Highest rates of
      GTP hydrolysis have been achieved at 81 degreesC in presence of 0.1-1 mm Mg2+.
      GTP hydrolysis is significantly inhibited by high glycerol concentrations, and
      the GTP hydrolysis rate also markedly decreases by addition of detergents. The Km
      for GTP is 13.7 microm at 70 degreesC and GTP hydrolysis is strongly inhibited by
      GDP (Ki = 8 microm). A. ambivalens Ffh, which includes an RNA-binding motif in
      the C-terminal domain, is shown to bind specifically to 7S RNA of the related
      crenarchaeote Sulfolobus solfataricus. Comparative sequence analysis reveals the
      presence of typical signal sequences in plasma membrane as well as extracellular
      proteins of hyperthermophilic crenarchaea which strongly supposes recognition
      events by an Ffh containing SRP-like particle in these organisms.

PMID- 9914524
TI  - Structure of the human beta2-glycoprotein I (apolipoprotein H) gene.
AB  - The gene encoding the human plasma protein beta2-glycoprotein I or apolipoprotein
      H was cloned and its structure determined. The gene which consists of eight exons
      was shown to span 18 kb and was localized to chromosome 17q23-24. The
      transcriptional initiation site was assigned to a position 31 bp upstream of the
      start codon. Several consensus sequence elements relevant for regulation of
      transcription in liver were seen in the 5'-upstream region of the gene. Exon 1
      contains the 5'-UTR together with the signal peptide coding sequences. Short
      consensus repeats (SCRs) 1, 3, 4, and 5 are encoded by single exons each while
      SCR2 is encoded by two exons. Exon 8 comprises the region encoding the C-terminal
      end of beta2-glycoprotein I (from His-310), the stop codon and the 3'-UTR.

PMID- 9914526
TI  - Binding of heptapeptides or unfolded proteins to the chimeric C-terminal domains
      of 70-kDa heat shock cognate protein.
AB  - Seventy-kDa heat shock cognate protein (hsc70) and its homologs in bacteria,
      yeast and vertebrates are known to form complexes with S-carboxymethyl-alpha
      lactalbumin (CMLA), an unfolded protein; and, this activity has been attributed
      to its C-terminal 30-kDa domain. Herein, we show that hsc70s isolated from the
      seeds of mung bean and peas, however, are not effective in complexing with CMLA,
      and that the 30-kDa domain of Arabidopsis hsc70 (At30) cannot form stable
      complexes with CMLA either. Moreover, chimeric 30-kDa domains, either composed of
      rat 18-kDa and Arabidopsis 10-kDa subdomains (R18At10) or with Arabidopsis 18-kDa
      and rat 10-kDa subdomains (At18R10), were prepared and tested for their ability
      to complex with CMLA or a heptapeptide FYQLALT. At18R10 cannot complex with both
      CMLA and FYQLALT. On the other hand, R18At10 is capable of forming complexes with
      FYQLALT at a level similar to that of the rat 30-kDa domain (R30). R18At10 also
      forms complexes with CMLA, but the amount of the R18At10/CMLA complexes is much
      less than that of R30/CMLA. The results imply that the 18-kDa subdomain dictates
      the binding specificity for heptapeptide, and that the C-terminal 10-kDa
      subdomain may also provide some selection or restriction for unfolded proteins to
      form complexes with hsc70.

PMID- 9914527
TI  - Amino acid sequences of lysozymes newly purified from invertebrates imply wide
      distribution of a novel class in the lysozyme family.
AB  - Lysozymes were purified from three invertebrates: a marine bivalve, a marine
      conch, and an earthworm. The purified lysozymes all showed a similar molecular
      weight of 13 kDa on SDS/PAGE. Their N-terminal sequences up to the 33rd residue
      determined here were apparently homologous among them; in addition, they had a
      homology with a partial sequence of a starfish lysozyme which had been reported
      before. The complete sequence of the bivalve lysozyme was determined by peptide
      mapping and subsequent sequence analysis. This was composed of 123 amino acids
      including as many as 14 cysteine residues and did not show a clear homology with
      the known types of lysozymes. However, the homology search of this protein on the
      protein or nucleic acid database revealed two homologous proteins. One of them
      was a gene product, CELF22 A3.6 of C. elegans, which was a functionally unknown
      protein. The other was an isopeptidase of a medicinal leech, named destabilase.
      Thus, a new type of lysozyme found in at least four species across the three
      classes of the invertebrates demonstrates a novel class of protein/lysozyme
      family in invertebrates. The bivalve lysozyme, first characterized here, showed
      extremely high protein stability and hen lysozyme-like enzymatic features.

PMID- 9914528
TI  - Decreased ATP synthesis is phenotypically expressed during increased energy
      demand in fibroblasts containing mitochondrial tRNA mutations.
AB  - Mutations in the tRNA genes of mitochondrial DNA (mtDNA) cause the debilitating
      MELAS (mitochondrial, myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes) and MERRF (myoclonic epilepsy and ragged-red fibres) syndromes. These
      mtDNA mutations affect respiratory chain function, apparently without decreasing
      cellular ATP concentration [Moudy et al. (1995) PNAS, 92, 729-733]. To address
      this issue, we investigated the role of mitochondrial ATP synthesis in
      fibroblasts from MELAS and MERRF patients. The maximum rate of mitochondrial ATP
      synthesis was decreased by 60-88%, as a consequence of the decrease in the proton
      electrochemical potential gradient of MELAS and MERRF mitochondria. However, in
      quiescent fibroblasts neither ATP concentration or the ATP/ADP ratio was affected
      by the lowered rate of ATP synthesis. We hypothesized that the low ATP demand of
      quiescent fibroblasts masked the mitochondrial ATP synthesis defect and that this
      defect might become apparent during higher ATP use. To test this we simulated
      high energy demand by titrating cells with gramicidin, an ionophore that
      stimulates ATP hydrolysis by the plasma membrane Na+/K+-ATPase. We found a
      threshold gramicidin concentration in control cells at which both the ATP/ADP
      ratio and the plasma membrane potential decreased dramatically, due to ATP demand
      by the Na+/K+-ATPase outstripping mitochondrial ATP synthesis. In MELAS and MERRF
      fibroblasts the corresponding threshold concentrations of gramicidin were 2-20
      fold lower than those for control cells. This is the first demonstration that
      cells containing mtDNA mutations are particularly sensitive to increased ATP
      demand and this has several implications for how mitochondrial dysfunction
      contributes to disease pathophysiology. In particular, the increased
      susceptibility to plasma membrane depolarization will render neurons with
      dysfunctional mitochondria susceptible to excitotoxic cell death.

PMID- 9914529
TI  - Modification of the unfolding region in bovine pancreatic ribonuclease and its
      influence on the thermal stability and proteolytic fragmentation.
AB  - Ribonuclease (RNase) A and the more stable glycosylated RNase B differ by a
      carbohydrate moiety (GlcNAc2Man5-9) attached to Asn34. As previously shown, the
      first proteolytic cleavage sites to appear on thermal denaturation of both
      enzymes are in the structural region around Asn34. To discriminate the
      contribution of the modifying moiety to the stabilization toward thermal
      unfolding, on the one hand, and proteolytic fragmentation, on the other hand, the
      carbohydrate chain of RNase B was shortened by treatment with glycosidases to
      obtain GlcNAc-RNase and (GlcNAc)2Man3 -RNase and extended by binding to
      concanavalin A or concanavalin A-agarose. The results show a saltatory increase
      of the thermal unfolding constants and transition temperatures of GlcNAc-RNase in
      comparison to RNase A, whereas the extension of the modification at Asn34 in the
      other RNase species does not further increase thermal stability. Therefore, the
      stability difference between RNase A and RNase B derivatives is attributed to the
      first carbohydrate unit. In contrast, the rate of proteolysis decreases gradually
      with increasing volume of the modifying moiety. As concluded from the analysis of
      the primary cleavage fragments, the main degradation pathway is shifted from the
      Asn34-Leu35 to the Thr45-Phe46 peptide bond due to increasing shielding effects.

PMID- 9914530
TI  - Assembly and secretion of recombinant chains of human inter-alpha-trypsin
      inhibitor in COS-7 cells.
AB  - The inter-alpha-trypsin inhibitor (ITI) family is a group of structurally related
      plasma serine protease inhibitors. The ITI family members consist of combinations
      of mature heavy chains named HC1, HC2, HC3 linked to bikunin (a Kunitz-type
      protease inhibitor) by a covalent interchain protein-glycosaminoglycan-protein
      cross-link. The biosynthesis of the ITI family members takes place in the liver.
      In this report we examine the biosynthesis of these proteins using transient
      transfected COS-7 cells expressing one or more combinations of human ITI chains.
      The processing and secretion of alpha1-microglobulin and bikunin does not require
      the ITI heavy chains. A small proportion of the H3 chain seems to be processed
      into the HC3 form in the absence of the other ITI chains. In contrast, the
      processing of H2 into HC2 needs the presence of the L chain. The COS-7 cells are
      able to link the HC2 and HC3 heavy chains with bikunin by means of a chondroitin
      sulfate bridge, and thus to generate 260-kDa ITI-like proteins as well as pre
      alpha-trypsin inhibitor (PalphaI). However, the maturation of the Hl chain into
      HC1 and the assembly of HC1 inside multichain proteins may take place according
      to a mechanism which differs from that of the H2 and H3 chains. These results
      indicate that the assembly of the constituent chains of the ITI-like proteins and
      PalphaI is not dependent on the liver machinery.

PMID- 9914531
TI  - Biochemical characterization, molecular cloning and expression of laccases - a
      divergent gene family - in poplar.
AB  - The nature of the enzyme(s) involved in the dehydrogenative polymerization of
      lignin monomers is still a matter of debate. Potential candidates include
      laccases which have recently received attention due to their capacity to oxidize
      lignin monomers and close spatial and temporal correlation with lignin
      deposition. We have characterized two H2O2-independent phenoloxidases with
      approximate molecular masses of 90 kDa and 110 kDa from cell walls of Populus
      euramericana xylem that are capable of oxidizing coniferyl alcohol. The 90-kDa
      protein was purified to apparent homogeneity and extensively characterized at the
      biochemical and structural levels. To our knowledge, this is the first report of
      a plant laccase purified to homogeneity from a lignifying tissue of an
      angiosperm. The cDNA clones corresponding to the 90-kDa and 110-kDa proteins,
      lac90 and lac110, were obtained by a PCR-based approach using specific
      oligonucleotides derived from peptide sequences. Sequence analysis indicated that
      lac90 and lac110 encoded two distinct laccases. In addition, heterologous
      screening using an Acer pseudoplatanus laccase cDNA enabled us to obtain three
      additional cDNAs (lac1, lac2, lac3) that did not correspond to lac90 and lac110.
      The five laccase cDNAs correspond to a highly divergent multigene family but
      Northern analysis with gene-specific probes indicated that all of the genes are
      exclusively and abundantly expressed in stems. These results highlight the
      polymorphism of plant laccases by an integrated biochemical and molecular
      approach, and provide the tools that will enable us to clearly determine the
      function of these enzymes in plants by molecular and genetic approaches.

PMID- 9914532
TI  - Secretion of human meprin from intestinal epithelial cells depends on
      differential expression of the alpha and beta subunits.
AB  - Human meprin (N-benzoyl-l-tyrosyl-p-aminobenzoic acid hydrolase, EC 3.4.24.18),
      an astacin-type metalloprotease, is expressed by intestinal epithelial cells as a
      dimeric protein complex of alpha and beta subunits. In transfected cells,
      intracellular proteolytic removal of the membrane anchor from the alpha subunit
      results in its secretion, while the beta subunit and alpha/beta heterodimers are
      retained at the cell membrane. We investigated the consequence of differential
      intracellular processing of alpha and beta subunits in the human small and large
      intestine using subunit-specific immunohistochemistry, in situ hybridization and
      biosynthetic studies in organ culture. In the ileum, both subunits localize to
      the brush-border membrane of villus enterocytes. In contrast, the beta subunit is
      not expressed in the colon, which leads to the secretion of the alpha subunit. We
      conclude that differential expression of meprin alpha and beta subunits is a
      unique means of targeting the proteolytic activity of the alpha subunit either to
      the brush-border membrane in the ileum or to the lumen in the colon, suggesting
      dual functions of cell-associated and luminal meprin. Meprin alpha and beta
      subunits are also coexpressed in distinct lamina propria leukocytes, suggesting
      an additional role for this protease in leukocyte function in the intestinal
      mucosa.

PMID- 9914533
TI  - Aggregation of hsp70 and hsc70 in vivo is distinct and temperature-dependent and
      their chaperone function is directly related to non-aggregated forms.
AB  - We used non-denaturing gradient analysis of cell extracts before and after heat
      treatment of the cells and showed that hsp70 and hsc70 aggregate in vivo in a
      temperature-dependent fashion. Their aggregation profiles were found to be
      clearly distinguishable and sensitive to ATP depletion. Pore exclusion limit
      electrophoresis showed that these two proteins are mainly found in autoaggregated
      forms including dimers, trimers and oligomers. The addition of denatured
      luciferase to the cell extracts reversed the aggregation of both proteins towards
      their non-aggregated forms. Immunoprecipitation and Western-blot analysis showed
      that the non-aggregated form is the only one bound to denatured luciferase. Our
      results suggest that aggregated hsp70 and hsc70 represent predominantly self
      associated molecules unable to exert chaperone activity. The cochaperone hsp40
      was also found to be aggregated and, on addition of denatured luciferase, its
      aggregation was reversed to a non-aggregated state. Immunoprecipitation analysis
      indicated that hsp40 forms a complex with the non-aggregated form of hsc70 and
      denatured luciferase. These results confirm previous in vitro studies and support
      the suggestion that in vivo cytosolic hsp70 and hsc70 exist mainly in an oligomer
      monomer equilibrium which is dependent on the environmental temperature, the
      levels of ATP and the presence of denatured proteins.

PMID- 9914534
TI  - The gelatin-binding site of the second type-II domain of gelatinase A/MMP-2.
AB  - We have shown previously that all three fibronectin type-II modules of gelatinase
      A contribute to its gelatin affinity. In the present work the second type-II
      module was subjected to site-directed mutagenesis in order to localize its
      gelatin-binding site. The functional integrity of mutant proteins was assessed by
      their affinity for gelatin using gelatin-Sepharose affinity chromatography. The
      structural integrity of the mutant proteins, i.e. their resistance to thermal and
      chaotropic agent-induced denaturation, was characterized by CD spectroscopy. Our
      studies show that, in the case of mutants R19L, R38L, K50G, K50R and R19L/R38L,
      the mutations had no significant effect on the structure and gelatin affinity of
      the type-II module, excluding the direct involvement of these residues in ligand
      binding. In the case of mutants Y25A, Y46A, D49A and Y52A, the mutations yielded
      proteins that were devoid of gelatin affinity. Structural characterization of
      these proteins, however, indicated that they had also lost their ability to fold
      into the native structure characteristic of the wild-type domain. In the case of
      mutant Y37A, the structure and stability of the mutant protein is similar to the
      wild-type module. However, its gelatin affinity was severely impaired compared
      with the wild-type protein. The fact that the Y37A mutation impairs ligand
      binding without detectable distortion of the module's architecture suggests that
      Y37 is directly involved in ligand binding. Homology modeling based on the three
      dimensional structure of the second type-II module of PDC-109 places Y37 on the
      right-hand rim of a hydrophobic pocket that includes residues F20, W39, Y46, Y52
      and F54, and thus provides proof for the involvement of this pocket in ligand
      binding.

PMID- 9914535
TI  - Replacement of terminal cysteine with histidine in the metallothionein alpha and
      beta domains maintains its binding capacity.
AB  - To generate novel forms of metal-binding proteins, six mutant mouse
      metallothionein (MT) 1 fragments, in which a terminal cysteine residue was
      replaced by histidine, were expressed in Escherichia coli. The spectroscopic and
      analytical results showed that the alphaMT (C33H, C36H, C41H, C57H) and betaMT
      (C5H, C13H) mutant forms bound 4 and 3 Zn(II) atoms per molecule of protein to
      the nearest integer, even though in C41H and C5H, species of lower stoichiometry
      were also detected. In Cd(II) titrations, all the Zn(II) ions bound to the mutant
      proteins were displaced from the binding sites, giving rise to Cd-mutated MT
      forms with 4 and 3 Cd(II), respectively. However, although Cys-to-His
      substitutions maintained the binding capacity of the MT fragments, they caused
      structural changes with respect to the wild-type proteins. While C13H, C36H and
      C57H seem to contain Zn(II)-aggregates that are closely related to those of the
      wild-type proteins, only C41H and C57H gave rise to Cd(II)-aggregates similar to
      those of Cd4-alphaMT, where the His residue plays the role of the substituted
      Cys. Despite the structural implications of the Cys-to-His replacement, the
      dissociation constants showed no major decrease in the Cd-binding affinity in any
      of the mutants assayed compared with the wild-type.

PMID- 9914536
TI  - The differential specificity of chymotrypsin A and B is determined by amino acid
      226.
AB  - The A and B isoforms of the pancreatic serine proteinase, chymotrypsin are known
      to cleave substrates selectively at peptide bonds formed by some hydrophobic
      residues, like tryptophan, phenylalanine and tyrosine. We found, however, that
      the B forms of native bovine and recombinant rat chymotrypsins are two orders of
      magnitude less active on the tryptophanyl than on the phenylalanyl or tyrosyl
      substrates, while bovine chymotrypsin A cleaves all these substrates with
      comparable catalytic efficiency. Analysing the structure of substrate binding
      pocket of chymotrypsin A prompted us to perform an Ala226Gly substitution in rat
      chymotrypsin B. The specificity profile of the Ala226Gly rat chymotrypsin B
      became similar to that of bovine chymotrypsin A suggesting that only the amino
      acid at sequence position 226 is responsible for the differential specificities
      of chymotrypsin A and B isoenzymes.

PMID- 9914537
TI  - Evolution of thyroid hormone binding by transthyretins in birds and mammals.
AB  - Transthyretin, a protein synthesized and secreted by the choroid plexus and
      liver, binds thyroid hormones in extracellular compartments. This binding
      prevents accumulation of thyroid hormones in the lipids of membranes,
      establishing extracellular thyroid hormone pools for the distribution of the
      hormones throughout the body and brain. The N-termini of the transthyretin
      subunits are longer and more hydrophobic in chicken than in eutherian
      transthyretins. Here, we show that this is a general structural feature of avian
      transthyretins. Systematic changes of protein structure during evolution result
      from selection pressure leading to changes in function. The evolution of
      transthyretin function, namely, the binding of thyroid hormones, was studied in
      nine vertebrate species. The affinity of thyroxine binding to transthyretin is
      lowest in avians (mean Kd of about 30 nm), intermediate in metatherians (mean Kd
      of about 17 nm) and highest in eutherians (mean Kd of about 11 nm). The affinity
      for 3,5,3'-triiodothyronine shows an opposite trend, being four times higher for
      avian transthyretins than for mammalian transthyretins.

PMID- 9914538
TI  - Depletion of Escherichia coli 4.5S RNA leads to an increase in the amount of
      protein elongation factor EF-G associated with ribosomes.
AB  - In Escherichia coli, 4.5S RNA is found in complexes with both protein
      translocation protein, Ffh (a bacterial homolog of mammalian SRP54) and protein
      synthesis elongation factor G (EF-G). To analyze the function of 4.5S RNA in
      translation, we initially assessed the sensitivity of the association of 4.5S RNA
      with the ribosome after treatment with antibiotics that affect various stages of
      protein synthesis. Fusidic acid and viomycin caused 4.5S RNA to cosediment with
      the 70S ribosomal fraction, indicating that 4.5S RNA enters the ribosome before
      ribosomal translocation and release of EF-G-GDP from the ribosome. On the other
      hand, depletion of 4.5S RNA led to the retention of a significant amount of EF-G
      on 70S ribosomes. In addition, 4.5S RNA shares a conserved decanucleotide
      sequence (58GAAGCAGCCA67) motif with the characterized EF-G-binding site at
      positions 1068-1077 on 23S RNA. We therefore examined by gel mobility-shift assay
      whether or not mutations in the domain-IV region of 4.5S RNA, including this
      conserved motif, disturb the binding of EF-G to 23S RNA. Any mutation at the C62,
      G64 or A67 residues within this motif abolished competition activity. Therefore,
      we propose that 4.5S RNA is concerned with the mode of association of EF-G with
      the ribosomes. Moreover, this function depends on the secondary structure of 4.5S
      RNA as well as a ten-base sequence conserved between the two RNAs.

PMID- 9914540
TI  - SUPPLEMENTARY MATERIAL: crystal state and solution conformation of the B blood
      group trisaccharide alpha-l-fucp-(1-->2)-

PMID- 9914541
TI  - A qualitative explanation of the Weber test.

PMID- 9914542
TI  - Traumatic optic neuropathy: result in 45 consecutive surgically treated patients.
AB  - The management of traumatic optic neuropathy remains controversial. In this
      report, we present the results of 45 patients treated with extracranial optic
      nerve decompression after at least 12 to 24 hours of corticosteroid therapy
      without improvement. Vision improved in 32 patients after surgery (71%), and the
      mean percentage of improvement from preoperative visual deficit was 40.7% +/-
      6.9% (median improvement 41.2%). Worsening of vision occurred in none of the
      patients as a result of the surgery, and no intraoperative or postoperative
      complications were encountered. We present a treatment protocol for traumatic
      optic neuropathy with the use of megadose corticosteroids and optic nerve
      decompression.

PMID- 9914543
TI  - Vestibular compensation in guinea pigs given intravenous lidocaine after
      unilateral labyrinthectomy.
AB  - Intravenous lidocaine has been reported to alleviate vertigo in Meniere's disease
      and suggested as a possible antivertigo agent after unilateral labyrinthectomy in
      a study of cats. To further evaluate the effects of intravenous lidocaine on the
      acute phase of postural compensation, we subjected 13 pigmented guinea pigs to
      unilateral labyrinthectomy. Seven received intravenous lidocaine (4 mg/kg)
      immediately after labyrinthectomy. The other six served as controls and received
      an equivalent-volume injection of normal saline solution. Total body curvature,
      trunk curvature, yaw head tilt, and roll head tilt were measured at frequent
      intervals for up to 30 hours after surgery. Both groups had immediate
      difficulties with posturing that gradually improved. The lidocaine group tended
      to exhibit delayed postural compensation, but this was only statistically
      significant for roll head tilt. These results do not show improvement in postural
      compensation from unilateral labyrinthectomy after the administration of
      intravenous lidocaine. A species-specific effect on the vestibular pathways is
      suggested, and we conclude that further evaluation of lidocaine and the
      vestibular system is warranted.

PMID- 9914544
TI  - Treatment of malignant neoplasms of the lateral cranial base with the combined
      frontotemporal-anterolateral approach: five-year follow-up.
AB  - Technical advances in accessing the lateral cranial base have permitted disease
      in this area previously deemed inoperable to be resected. The procedures required
      to effect an oncologically adequate resection are often long and accompanied by
      the potential for serious, even life-threatening, complications. Although it has
      been demonstrated that such disease can be extirpated, the question of whether
      such heroic surgery improves long-term survival remains unanswered. We
      retrospectively reviewed the records of 25 patients who underwent a combination
      of frontotemporal craniotomy with other, more conventional, anterolateral
      procedures (eg, infratemporal fossa approach, maxillectomy, orbitectomy,
      mandibulopharyngectomy) to resect stage IV malignant disease of the lateral to
      midcranial base between 1983 and 1990. Perioperative deaths occurred in 2
      patients, 1 patient died of unrelated causes free of disease, and 2 patients were
      lost to follow-up, leaving 20 patients with a minimum 5-year evaluation. Five
      (25%) of the 20 patients we monitored were free of disease. Of those patients in
      whom recurrent disease developed, local control was achieved in about 50%;
      however in 80% of those with recurrence, metastatic disease developed. Surgical
      treatment of selected stage IV malignant disease of the lateral to midcranial
      base appears to have provided long-term disease-free survival to 25% of patients
      in this series who would otherwise have had little hope of survival.

PMID- 9914545
TI  - Early diagnosis and treatment of laryngeal injuries from prolonged intubation in
      adults.
AB  - Prolonged endotracheal intubation can cause injuries to 1 or more regions of the
      larynx, making safe extubation impossible and leading to tracheostomy in many
      patients. Unfortunately, a considerable number of these patients do not benefit
      from early laryngeal evaluation, which may reveal potentially treatable soft,
      obstructive tissue before it undergoes irreversible fibrosis. Between July 1992
      and December 1995, we performed immediate direct telelaryngoscopy on 142 adults
      who required tracheostomy because of failed extubation. When present, obstructive
      tissue was removed with microsurgical techniques. One hundred twenty-nine (90%)
      patients were decannulated within 3 weeks. The 2 main reasons for failure of
      early decannulation were intractable granulation (in patients with insulin
      dependent diabetes) and coexisting tracheal stenosis. Immediate telelaryngoscopy
      is recommended in all patients who require tracheostomy because of failed
      extubation. Flexible laryngoscopy is not adequate for thorough assessment of
      laryngeal damage from prolonged intubation.

PMID- 9914546
TI  - Current treatment practices for early laryngeal carcinoma.
AB  - OBJECTIVE: Controversy regarding the management of early laryngeal carcinoma
      persists in the absence of a definitive comparison of treatment modalities. This
      study examines the basic management practices for early laryngeal cancer among
      the American Academy of Otolaryngology-Head and Neck Surgery membership with an
      emphasis on the role of conservation surgery. METHODS: Questionnaires were
      randomly distributed to 3000 members with 1000 responses. The results were
      collated and statistically evaluated with multivariable frequency analysis.
      RESULTS: For operable supraglottic tumors, supraglottic laryngectomy was
      advocated by 41.6% of those responding. Definitive radiation therapy was
      suggested by 5.3% of participants and total laryngectomy by 1.4%. Explanation of
      treatment options with the patient deciding the therapy was selected by 48.3% of
      responders. For suitable glottic tumors, hemilaryngectomy was recommended by
      37.1%, definitive radiation therapy by 8.1%, total laryngectomy by 1.9%, and
      patient choice by 50.4% of members completing the survey. When patients were left
      to weigh the treatment options, surgery was much less likely to be chosen than if
      it was advocated by the physician. Trends were evident according to practice
      region and setting, but these variables did not correlate strongly with physician
      recommendations. However, date of residency completion and rating of available
      radiation oncology services were significant factors. The evaluation of
      postoperative considerations in laryngeal conservation surgery demonstrated large
      variability in the definition of a close margin and the perceived need for
      additional therapy. CONCLUSIONS: The varied practice patterns among the American
      Academy of Otolaryngology-Head and Neck Surgery membership reflect the lack of a
      comparative outcome analysis for the treatment of early laryngeal carcinoma.
      Consequently, the full reliance on patient choice, which is more pronounced among
      young physicians, and cost considerations may have the greatest impact on the
      future treatment of this disease.

PMID- 9914547
TI  - Clinical-severity staging system for oral cavity cancer: five-year survival
      rates.
AB  - The objective of this research is to improve the classification and survival
      estimates for patients with oral cavity cancer by combining cancer symptom
      severity and comorbidity with the current TNM staging system. The study design is
      a retrospective medical record review that uses explicit coding criteria. The
      medical records of 277 patients receiving initial treatment at the Washington
      University Medical Center between 1980 and 1989 were reviewed. Multivariate
      analysis identified patient factors that significantly affected 5-year survival.
      These patient factors, symptom severity and comorbidity, were combined with TNM
      to create a composite clinical-severity staging system. The overall 5-year
      survival rate was 46% (128/277). Survival rates by TNM stage were as follows:
      stage I, 72% (36/50); II, 54% (45/84); III, 37% (24/65); and IV, 29% (23/78)
      (chi2 = 25.27, P = 0.001). When patients were grouped according to the clinical
      severity staging system, survival rates were as follows: stage I, 77% (33/43);
      II, 56% (45/80); III, 42% (43/103); and IV, 14% (7/51) (chi2 = 40.62, P = 0.001).
      Survival estimates can be improved by adding carefully studied and suitably
      defined patient variables to the TNM system. The current TNM staging system for
      oral cavity cancer is based solely on the morphologic description of the tumor
      and disregards the clinical condition of the patient. Patient factors, such as
      cancer symptom severity and comorbidity, have a significant impact on survival.
      Continued exclusion of patient factors leads to imprecision in prognostic
      estimates and hinders interpretation of clinical studies.

PMID- 9914548
TI  - Effect of temperature on lateral wall mechanics of the guinea pig outer hair
      cell.
AB  - The outer hair cell is thought to enhance the sensitivity of mammalian hearing.
      Its lateral wall consists of 3 concentric layers: an outermost plasma membrane, a
      cortical lattice, and an innermost collection of flattened membranes called the
      subsurface cisternae. The cytoplasm requires positive pressure for full
      expression of the outer hair cell's electromotility. Using micropipette
      aspiration, we investigated the mechanics of the guinea pig's outer hair cell
      lateral wall at room temperature (22 degrees C) and at the guinea pig's body
      temperature (39 degrees C). Although there was a 10% decrease in stiffness
      parameter with an increase from room to body temperature, the difference was not
      statistically significant; values ranged from 0.45 to 0.65 dyne/cm. With
      sufficient negative pressure, the cytoplasmic membrane is separated from the rest
      of the outer hair cell's lateral wall, a process that leads to vesiculation of
      the plasma membrane. Vesiculation occurs at a lower pressure than at body
      temperature. Our results demonstrate that the stiffness parameter of the outer
      hair cell lateral wall at body temperature is similar to that at room
      temperature. However, the plasma membrane's attachment to the cortical lattice is
      greatly altered by temperature. The decrease in strength of membrane attachment
      at body temperature may result from a change in membrane fluidity, making it more
      easy for membrane attachment sites to break free and permit vesiculation. Whether
      the tethering of the plasma membrane to the cortical lattice is lost under
      clinically pathologic conditions deserves future study.

PMID- 9914549
TI  - Utility of portable chest radiographs as a predictor of endotracheal tube cuff
      pressure.
AB  - Increased endotracheal tube cuff pressure causes mucosal ischemia that can lead
      to necrosis, infection, and, eventually, tracheomalacia or tracheal stenosis.
      Endotracheally intubated patients frequently undergo portable chest radiography.
      In this study we explored the relationship of endotracheal tube cuff pressure and
      the appearance on the tracheal air columns on the portable chest radiograph. We
      measured the endotracheal tube cuff pressure of intensive care unit patients 124
      times immediately before portable chest radiography. On 64 of these radiographs
      we measured the width of the tracheal air column below the tip of the
      endotracheal tube and at the maximal diameter of the endotracheal tube balloon.
      We then analyzed the relationship of cuff pressure to tracheal dilation. The
      results of ANOVA of tracheal dilation for three groups (safe, borderline, and
      unsafe cuff pressures) were significant. Large overlapping ranges existed in each
      group. Regression analysis confirmed a linear relationship between cuff pressure
      and tracheal dilation (r = 0.435, p < 0.001). Predicted tracheal expansion at 20
      mm Hg was a poor screen for endotracheal tube cuff inflation safety; the
      sensitivity was only 56% and specificity only 71%. The differences in the
      capacity for tracheal distension between patients make these findings not
      unexpected. The portable chest radiograph is a poor screening tool for unsafe
      endotracheal tube cuff pressure.

PMID- 9914550
TI  - Selection of antibiotics after incision and drainage of peritonsillar abscesses.
AB  - Despite the fact that peritonsillar abscess is the most common complication of
      acute tonsillitis, the treatment of peritonsillar abscess remains controversial.
      One element of controversy is the choice of antibiotics after drainage of the
      abscess. In an attempt to assess the effect of antibiotic choice on the treatment
      of peritonsillar abscess, we conducted a retrospective review of records from
      patients with peritonsillar abscess treated with incision and drainage. Our
      review identified 103 patients, comprising two groups: 58 patients treated with
      broad-spectrum intravenous antibiotics and 45 patients treated with intravenous
      penicillin alone. These patients were hospitalized after incision and drainage,
      and therefore their clinical courses and responses to therapy could be rigorously
      assessed. Characterization of illness based on patient age, temperature, and
      white blood cell count revealed similar severity of illness between the two
      groups. Comparison of clinical outcomes with respect to hours hospitalized (mean
      44.3 +/- 6.6 and 38.3 +/- 7.1 hours, 95% confidence interval, for broad-spectrum
      and penicillin groups, respectively) and mean hours febrile (16.9 +/- 5.0 and
      13.3 +/- 4.2 hours, 95% confidence interval) were not statistically significantly
      different (p = 0.222 and 0.269, respectively) between groups, indicating that
      broad-spectrum antibiotics failed to show greater efficacy than penicillin in the
      treatment of these patients. The microbiologic characteristics of these
      infections, failures of therapy, and complication rates were similar to those
      reported in the literature. These results suggest that intravenous penicillin
      remains an excellent choice for therapy in cases of peritonsillar abscess
      requiring parenteral antibiotics after drainage.

PMID- 9914551
TI  - Teleconsultation in otolaryngology: live versus store and forward consultations.
AB  - OBJECTIVE: To evaluate the relative strengths and weaknesses of interactive and
      delayed teleconsultations in otolaryngology. SETTING: Ambulatory clinic at an
      urban tertiary care facility. SUBJECTS: Forty-five adult patients with known or
      suspected upper aerodigestive tract pathology. INTERVENTION: Patients were
      interviewed by an otolaryngology chief resident (CR) using a standardized
      protocol; the results were presented to a board-certified otolaryngologist
      present locally (LBCO) and a remote physician viewing the encounter by video
      conferencing elsewhere in the hospital (RBCO). The CR performed a complete
      otolaryngologic examination, including fiberoptic nasopharyngolaryngoscopy. The
      CR and LBCO viewed the examination on a video monitor; the RBCO viewed the same
      image on the video-conferencing monitor. Each physician independently recorded
      findings and rendered a diagnosis. A third board-certified otolaryngologist, who
      reviewed the stored data file (text and stored images) in a delayed fashion
      (DBCO), documented his findings and made a diagnosis. RESULTS: The CR and LBCO
      agreed on diagnosis in 92% (36 of 39) of cases. The LBCO and RBCO arrived at the
      same diagnosis in 29 of 34 (85%) cases. The DBCO agreed with the LBCO for 18 of
      28 (64%) diagnoses. Agreement on management recommendations between the LBCO/DBCO
      pair were also lower than for the LBCO/RBCO pair. CONCLUSIONS: Both interactive
      and delayed techniques can be used to provide relatively accurate clinical
      consultations in otolaryngology. Telemedicine can be applied for subspecialty
      consultations, screening programs, remote emergency triage, second opinions, and
      resident education.

PMID- 9914552
TI  - Cell adhesion molecules in normal laryngeal development.
AB  - Larynges taken from normally developing rats ranging from embryos starting at
      embryonic day 10 to adults were harvested. Sections of the larynges were prepared
      with the use of immunohistochemical techniques with primary antibodies directed
      to the neural cell adhesion molecule; selected sections were exposed to
      antibodies directed against the embryonic polysialated form of the neural cell
      adhesion molecule and against L1. Cell adhesion molecules were present throughout
      embryonic development associated with the recurrent laryngeal nerve.
      Downregulation of expression was observed after postnatal day 14. We conclude
      that cell adhesion molecules may play a role in the normal neural development of
      the larynx in rats.

PMID- 9914553
TI  - Model for evaluating the effect of growth factors on the larynx.
AB  - Growth factors are proteins that help regulate the inflammatory response and
      wound healing in tissues. After laryngotracheal surgery, proper wound healing is
      important in maintaining the reconstructed airway. The application of growth
      factor to the respiratory mucosa of the larynx and its effect on wound healing
      within the airway have not been studied. This study was designed to establish a
      model for the evaluation of wound healing after the application of growth factor
      to composite respiratory mucosa and cartilage surfaces at the time of
      laryngotracheoplasty. Forty rabbits underwent anterior cricoid cartilage split
      with or without the use of a cartilage graft. Platelet-derived growth factor or a
      placebo substance was applied to the wound at the time of surgery. This study
      offers a model for studying wound healing in the airway that is reproducible with
      limited morbidity.

PMID- 9914555
TI  - Dysphagia caused by cervical osteophytes: three cases treated successfully by
      surgery.

PMID- 9914554
TI  - Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo.
AB  - Although the cyclooxygenase and lipoxygenase pathways of arachidonic acid
      metabolism have been shown to lead to osteoclastic resorption, the cytochrome
      P450 pathway has not been implicated. We investigated the effects of the
      cytochrome P450 pathway in IL-1beta-induced calcium release from cultured mouse
      calvaria in vitro in the presence of clotrimazole, a cytochrome P450 inhibitor,
      or L-N(G)-arginine methyl ester, a nitric oxide synthase inhibitor. Clotrimazole
      inhibited calcium release in a dose-dependent manner; however, L-N(G)-arginine
      methyl ester did not inhibit resorption. These results suggest that cytochrome
      P450 may be another possible mediator of IL-1beta-induced bone resorption in
      vitro. In the in vivo portion of the study, clotrimazole was administered in the
      gerbil model of adaptive bone modeling. Clotrimazole inhibited osteoclast
      surface; however, it did not reduce the osteoclast number, mean erosion surface
      per osteoclast, mineralization surface, or mineral-apposition rate. These results
      suggest that clotrimazole may inhibit the activation of osteoclasts and that
      cytochrome P450-dependent enzymes may be related to osteoclast activation in
      vivo.

PMID- 9914556
TI  - Cervicothoracic chordoma presenting as progressive dyspnea and dysphagia.

PMID- 9914557
TI  - Acute reconstruction of massive cervicofacial necrotizing fasciitis with
      Estlander and free scapular/parascapular flaps.

PMID- 9914558
TI  - Acute upper airway obstruction in achalasia.

PMID- 9914559
TI  - Use of a three-dimensional magnetic sensor in vestibular testing.

PMID- 9914560
TI  - New "seeing" stylet-scope and method for the management of the difficult airway.

PMID- 9914561
TI  - Effects of otitis media with effusion on the vestibular system in children.
AB  - Middle ear effusion has been considered the most common cause of vestibular
      disturbance in children. However, there have been only a few studies on
      vestibular disturbance in children with otitis media with effusion. We studied
      the vestibular systems of 30 children with otitis media with effusion aged 8 to
      13 years and compared the results with 15 age- and sex-matched controls. A
      questionnaire relating to vestibular disturbance was given to patients and their
      parents. Spontaneous nystagmus and positional nystagmus were recorded by
      electronystagmography as diagnostic tests of the vestibular system. Romberg's and
      past-pointing tests were performed on children with otitis media with effusion
      and controls. After vestibular tests were completed, myringotomy was performed,
      and a ventilation tube was inserted. The questionnaire and the vestibular tests
      were repeated after the operation and during the first month after surgery. Our
      study showed that there was a history of vestibular disturbance in 33% of
      children with otitis media with effusion. Electronystagmography and Romberg's
      test findings demonstrated that 33% of the children had vestibular dysfunction (p
      < 0.05). After myringotomy with ventilation tube insertion, vestibular test
      results returned to normal, and symptoms related to vestibular disturbance
      improved. These findings confirm the assumption that middle ear effusion may
      affect the vestibular system, which can be resolved after myringotomy with
      ventilation tube insertion.

PMID- 9914562
TI  - Retrosigmoid-transmeatal en bloc removal of small to medium-sized acoustic
      neuromas.
AB  - One hundred three subjects with acoustic neuroma (AN) underwent surgery-
      involving a retrosigmoid-transmeatal approach--between January 1990 and December
      1995. All the intracanalar tumors (n = 18) and 70 of the intra- and extracanalar
      neuromas with an extracanalar neuroma size less than 25 mm--a total of 88
      patients--constituted the final study population. The first 48 patients were
      operated on with the use of classic procedures described in the literature,
      characterized by limited exposure of the internal auditory canal and removal of
      the tumor after debulking. Surgery in the next 40 subjects was conducted
      according to the technique of en bloc removal of the tumor. The main features of
      this technique are continuous direct recording of cochlear and facial-nerve
      action potentials, wide opening of the internal auditory canal with lateral
      extension to the fundus, and removal of the tumor following the capsular lining
      without debulking. Statistical analysis of the results of the en bloc removal,
      compared with the previously used debulking technique, showed improvement in
      postoperative outcome for both auditory and facial-nerve function.

PMID- 9914563
TI  - Histologic study of the recurrent laryngeal nerve in spasmodic dysphonia.
AB  - It has been reported that there were no significant changes in the recurrent
      laryngeal nerves of patients with adductor spasmodic dysphonia, which could
      explain the cause of this disease. However, the researchers who made these
      reports appeared to have investigated only the extralaryngeal part of the nerve
      involved in the neck. Because the recurrent laryngeal nerve contains many
      components that distribute to various organs, we must study in greater detail a
      more peripheral part of the motor nerve, which has a much closer relationship to
      vocal cord movements. At the time of surgery we obtained specimens of the
      thyroarytenoid branches of the recurrent laryngeal nerves in two female patients
      with adductor spasmodic dysphonia. Although histologic analysis revealed no
      apparent signs of either destruction or degeneration, the percentage of thin
      nerve fibers, the diameter of which may range from 5 to 10 microm, was higher
      than in normal controls. This suggests the possibility of a neurologic
      abnormality in the larynges of ASD patients.

PMID- 9914564
TI  - Clinical photographs. Laryngeal sarcoidosis.

PMID- 9914565
TI  - Clinical photographs. Malignant melanoma of the ear in a child.

PMID- 9914566
TI  - Clinical photographs. Lymphoma of the tongue.

PMID- 9914567
TI  - Learning objectives for telemedicine applications in otolaryngology-head and neck
      surgery.

PMID- 9914568
TI  - Comparison of binge drinking among pregnant and nonpregnant women, United States,
      1991-1995.
AB  - Our goal was to measure the pregnancy-related reduction in the prevalence of
      reported binge drinking (>/=5 alcoholic drinks per occasion) and to characterize
      binge drinkers among pregnant and nonpregnant women aged 18-44 years, in the
      United States, 1991-1995. We used the Behavioral Risk Factor Surveillance System
      data from 46 states. We used the prevalence rate ratio between pregnant and
      nonpregnant women to determine the magnitude of the reduction in reported binge
      drinking and multiple logistic regression models to identify characteristics
      associated with binge drinking. Between 1991 and 1995, the prevalence of binge
      drinking among pregnant women increased significantly from 0.7% (95% confidence
      interval 0.2-0.9) to 2.9% (95% confidence interval 2.2-3.6), whereas among
      nonpregnant women the prevalence changed little (11.3% vs 11.2%). Over the study
      period pregnant women were one fifth (prevalence rate ratio 0.2, 95% confidence
      interval 0.1-0.2) as likely as nonpregnant women to binge drink. Among various
      population subgroups of women, pregnancy-related reduction in binge drinking was
      smallest among black women and largest among women aged </=30 years and among
      those who had quit smoking. Among pregnant women binge drinking was independently
      associated with being unmarried, being employed, and current smoking. Among
      nonpregnant women binge drinking was independently associated with age </=30
      years, nonblack race, college level education, being unmarried, being employed or
      a student, and current smoking. Clinicians serving women of childbearing age need
      to be aware of the recent rise in reported binge drinking during pregnancy, as
      well as the known risk factors for binge drinking.

PMID- 9914569
TI  - Uterine ultrasonographic changes with gonadotropin-releasing hormone agonists.
AB  - OBJECTIVES: Our purpose was to assess the changes in uterine volume and uterine
      artery pulsatility index in response to gonadotropin-releasing hormone agonist
      treatment in women undergoing hysterectomy for nonfibroid-related uterine
      bleeding. STUDY DESIGN: A double-blind, placebo-controlled randomized trial of 51
      women awaiting hysterectomy in a gynecology outpatient clinic was conducted. The
      women were treated for 8 weeks with either leuprolide acetate depot or placebo.
      Vaginal ultrasonographic examinations were performed before and after treatment.
      The paired t test was used for statistical analysis. RESULTS: In those allocated
      to therapy with gonadotropin-releasing hormone agonist the mean uterine volume
      decreased by 34% and the uterine artery pulsatility index increased from 2.25 to
      2.7. No significant changes were seen in the placebo group. The intersonographer
      variability was low and there was a high correlation between uterine size as
      measured by ultrasonography before hysterectomy and that measured
      postoperatively. CONCLUSIONS: Treatment with gonadotropin-releasing hormone
      agonists leads to uterine shrinkage and an increase in the uterine artery
      pulsatility index even in the absence of uterine fibroids.

PMID- 9914570
TI  - Effect of antibiotic use on the prevalence of symptomatic vulvovaginal
      candidiasis.
AB  - OBJECTIVE: The purpose of the study was to evaluate the influence of antibiotic
      use on the prevalence of symptomatic vulvovaginal candidiasis. STUDY DESIGN: This
      is a case-control study of 684 women with symptomatic vulvovaginal candidiasis
      who were enrolled at a vaginitis clinic and 901 control subjects who attended a
      cytologic screening service. RESULTS: The prevalence of antibiotic use in the
      month preceding the visit was 19.3% (132/684) among patients with Candida
      infection compared with 11.9% (107/901) among control subjects (P <.001). After
      adjustment by logistic regression for potential confounders (age, marital status,
      and contraceptive method used), the odds ratio for vulvovaginal candidiasis among
      patients who reported antibiotic use in the month preceding the visit was 1. 75
      (95% confidence interval 1.33 to 2.32). No differences in risk were found by type
      of antibiotic used. The likelihood of vulvovaginal candidiasis was directly
      related to the duration of antibiotic use and was higher in patients who had a
      history of repeated episodes of Candida vaginal infection. CONCLUSIONS:
      Antibiotic use is a short-term risk factor for symptomatic vulvovaginal
      candidiasis, either as a first episode or in the form of recurrence. Increasing
      duration of antibiotic use is directly related with an increased prevalence of
      Candida vaginal infection.

PMID- 9914571
TI  - Randomized controlled trial of the management of premenstrual syndrome and
      premenstrual mastalgia using luteal phase-only danazol.
AB  - OBJECTIVE: Our goal was to evaluate the efficacy and side effects of danazol 200
      mg daily given only in the luteal phase of the menstrual cycle to treat
      premenstrual syndrome and premenstrual mastalgia. STUDY DESIGN: We conducted a
      randomized, double-blind, placebo-controlled study of 3 menstrual cycles in a
      postgraduate medical school and National Health Service hospital. The subjects of
      the study were 100 women who had been referred to the premenstrual syndrome
      clinic at the North Staffordshire Hospital for the management of premenstrual
      syndrome and premenstrual breast pain. Outcome measures for the study included
      assessment of improvement in symptoms measured by specific daily visual analogue
      scales for 4 principal symptoms of premenstrual syndrome and for premenstrual
      mastalgia and assessment of side effects and adverse events. RESULTS: Significant
      improvement in symptoms was seen in visual analog scores for mastalgia in months
      1 (P =.03), 2 (P =.004), and 3 (P =.01) of the study during active therapy
      compared with placebo. No improvement was seen for any other symptom or for the
      global premenstrual syndrome score. Side effects on danazol and on placebo were
      equal and minimal. CONCLUSIONS: Luteal phase-only danazol is not effective for
      the treatment of the general symptoms of premenstrual syndrome but appears highly
      effective for the relief of premenstrual mastalgia. This approach to therapy is
      associated with few side effects. Studies of cyclic mastalgia using strict
      diagnostic criteria are required to see whether the freedom from symptomatic side
      effects is found in longer-term studies and to determine whether such a regimen
      avoids potentially detrimental effects on the lipid status.

PMID- 9914572
TI  - Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma,
      invasive Paget's disease, and recurrence after surgical excision.
AB  - OBJECTIVE: Our aim was to determine the prevalence of associated vulvar
      adenocarcinoma, invasive Paget's disease, and recurrence of Paget's disease of
      the vulva. STUDY DESIGN: A retrospective review of tumor and pathology registries
      at 8 institutions is presented. Patients with recurrent disease were excluded.
      Histologic slide review was performed. RESULTS: The median age of the 100
      patients was 70 years. The median duration of pruritus before surgery was 2
      years. Thirty-four percent of patients experienced a recurrence at a median of 3
      years. There was a 12% prevalence of invasive vulvar Paget's disease and a 4%
      prevalence of associated vulvar adenocarcinoma. One patient died of Paget's
      disease with associated vulvar adenocarcinoma. CONCLUSIONS: Paget's disease of
      the vulva is rarely associated with an underlying vulvar adenocarcinoma or
      invasive Paget's disease, but there is a high recurrence rate.

PMID- 9914573
TI  - Serum levels of macrophage colony-stimulating factor-1 in cervical human
      papillomavirus infection and intraepithelial neoplasia.
AB  - OBJECTIVE: Our goal was determine the correlation between serum colony
      stimulating factor-1 levels, cervical human papillomavirus infection, and
      dysplasia. STUDY DESIGN: Serum samples were obtained from control subjects from
      the United States and from a group of Panamanian women. Members of the latter
      group fell into 3 categories: those who serve as Panamanian control subjects and
      who test negative for human papillomavirus (n = 10); those who are high risk by
      history and test positive for human papillomavirus types 16/18 and 30s (n = 10);
      and those with the same high-risk history with biopsy-proven cervical
      intraepithelial neoplasia (n = 8). Serum colony-stimulating factor-1 levels were
      determined using enzyme-linked immunosorbent assay. Data were analyzed with the
      Student-Newman-Keuls and t tests. RESULTS: Mean serum colony-stimulating factor-1
      levels of patients with a positive test result for human papillomavirus (1166 +/-
      949 pg/mL) and cervical intraepithelial neoplasia (1295 +/- 314 pg/mL) were
      higher than those of control subjects from the United States (584 +/- 237 pg/mL)
      and those of Panamanian control subjects (520 +/- 229 pg/mL). Statistical
      analysis revealed the concentration of colony-stimulating factor in patients with
      positive test results for human papillomavirus or cervical intraepithelial
      neoplasia were significantly higher than in control groups. In addition,
      combining patients with human papillomavirus with those who have cervical
      intraepithelial neoplasia results in a group that has significantly higher colony
      stimulating factor levels compared with control subjects. CONCLUSIONS: Both high
      grade cervical dysplasia and high-risk human papillomavirus infection are
      associated with higher mean serum colony-stimulating factor levels, suggesting a
      possible role for colony-stimulating factor-1 in cervical neoplasia. Further
      studies are needed to understand the mechanism of colony- stimulating factor
      activation in human papillomavirus infection. This may assist in designing
      therapeutic approaches for the management of this disease.

PMID- 9914574
TI  - An illuminated vaginal speculum.
AB  - Examination of patients with genital prolapse in the dorsal supine position may
      be improved with the use of an illuminated vaginal speculum. Combining the light
      source of a laryngoscope with the blade of a Sims' speculum enables the vaginal
      walls to be carefully inspected at rest or during a Valsalva maneuver. Detection
      of loss of rugosity of the vaginal walls and defects in the pubocervical or
      rectovaginal fasciae may be facilitated with this instrument.

PMID- 9914575
TI  - Success rates and estimation of gestational age for medical abortion vary with
      transvaginal ultrasonographic criteria.
AB  - OBJECTIVE: Our purpose was to evaluate differences in gestational age and success
      rates for medical abortion patients obtained by using several nomograms for mean
      sac diameter and embryonic pole. STUDY DESIGN: A retrospective review of 1011
      patients was performed; the data were from 8 published studies and private
      patients of the primary author (M.D.C.) who received methotrexate and misoprostol
      for abortion. The ultrasonographic findings at baseline examination were used to
      estimate gestational age according to criteria established by Hellman et al and
      Rossavik et al for mean sac diameter and Robinson, Hadlock et al, and Goldstein
      and Wolfson for the embryonic pole. The assigned gestational ages of the study
      population were then compared, and the success rates of treatment at various
      gestational ages were calculated for each of the dating criteria. RESULTS:
      Outcomes on the basis of gestational age for those patients who had only a
      gestational sac were similar regardless of which gestational age criteria were
      used. The final assessment of gestational age by embryonic pole according to the
      criteria of Goldstein and Wolfson was significantly different from the others.
      CONCLUSIONS: Medical abortion outcomes will vary depending on which criteria are
      used for establishing gestational age by both mean sac diameter and embryonic
      pole.

PMID- 9914576
TI  - A new clinical option for hormone replacement therapy in women with secondary
      amenorrhea: effects of cyclic administration of progesterone from the sustained
      release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and
      withdrawal bleeding.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      2 doses of a transvaginal polycarbophil-based progesterone gel (4% and 8%) in
      hormone replacement therapy. STUDY DESIGN: This multicenter, randomized, parallel
      group, open-label 3-month study included 127 women with secondary amenorrhea.
      Estrogenized patients applied transvaginal progesterone (4% or 8%) every other
      day for 6 doses per month. Efficacy was based on endometrial biopsy findings and
      withdrawal bleeding. McNemar's test was used to compare incidence of adverse
      events before and during treatment. RESULTS: Progestational changes were found in
      92% (Crinone 4%) and 100% (Crinone 8%) of patients with evaluable biopsies.
      Withdrawal bleeding was experienced by 81% (Crinone 4%) and 82% (Crinone 8%) of
      the patients. No patient experienced any serious side effect related to
      treatment. The incidence of most side effects, including psychologic symptoms,
      decreased with progesterone treatment compared with estrogen alone therapy.
      Compliance exceeded 98% for both doses. CONCLUSIONS: Crinone is a novel,
      effective, and well-tolerated option for hormone replacement therapy in women
      with secondary amenorrhea.

PMID- 9914577
TI  - A new splenic artery Doppler velocimetric index for prediction of severe fetal
      anemia associated with Rh alloimmunization.
AB  - OBJECTIVE: We developed a new Doppler index for the noninvasive prediction of
      severe fetal anemia by means of Doppler velocimetry of the main splenic artery.
      STUDY DESIGN: Doppler velocimetry of the main splenic artery was performed in 85
      healthy fetuses and in 22 nonhydropic study case patients (41 measurements) at
      risk for anemia from Rh sensitization. The deceleration angle between the line
      describing the average slope during the diastolic phase of the cycle and the
      vertical axis was measured and expressed in multiples of the median (MoM) for
      gestational age. Severe anemia was defined as a hemoglobin deficit (mean
      hemoglobin for gestational age minus measured hemoglobin) >/=5 g/dL. Anemia
      overall was defined as a hemoglobin deficit >/=2 g/dL. RESULTS: Mean gestational
      age at cordocentesis was 28.6 weeks. Severe anemia was noted on 7 occasions
      (12.6%) and anemia was noted on 21 (51.2%) occasions. There was a significant
      correlation between deceleration angle and hemoglobin deficit >/=2 g/dL (r =
      0.5763, P <.0001) and also with hemoglobin deficit >/=5 g/dL (r = 0.6418, P
      <.0001). At deceleration angles <0. 90 MoM, a 90.5% sensitivity and a 30% false
      positive rate were achieved for anemia detection. At a threshold deceleration
      angle of <0.60 MoM, the sensitivity for severe anemia was 100%, with an 8.8%
      false-positive rate. CONCLUSION: We report a new and sensitive Doppler
      velocimetric technique for predicting severe anemia. By means of splenic artery
      velocimetry, all cases of severe anemia could be identified before the
      development of hydrops, with a >91% reduction in the rate of cordocentesis.

PMID- 9914578
TI  - A prospective, randomized comparison of Foley catheter insertion versus
      intracervical prostaglandin E2 gel for preinduction cervical ripening.
AB  - OBJECTIVE: The objective of this study was to compare intracervical prostaglandin
      E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical
      ripening. STUDY DESIGN: Women who came to the hospital for induction of labor
      with a Bishop score </=5 were randomly assigned to treatment with either
      prostaglandin E2 gel or a Foley bulb. Prostaglandin E2 gel was used according to
      the manufacturer's recommendation. The Foley group had a number 14 Foley catheter
      inserted, inflated, and placed on traction. Immediately after Foley bulb
      extrusion or 6 hours after prostaglandin E2 gel course completion, a dilute
      oxytocin solution was started if the patient was not in labor. RESULTS: Seventy
      seven women were entered into the Foley group and 72 were entered into the
      prostaglandin E2 gel group. Both the Bishop score after preinduction ripening
      (6.5 vs 5.1, P <.001) and the change in Bishop score (3.5 vs 2.7, P =.015) were
      significantly higher in the Foley group. There were no differences between the
      groups in mode of delivery, infant weight, rate of hyperstimulation, shoulder
      dystocia, patient discomfort, epidural use, oxytocin use, or nonreassuring fetal
      heart rate patterns. The preinduction time (9.9 vs 17.2 hours, P <.001) and the
      total induction time (22.4 vs 30.4 hours, P <.001) were significantly shorter in
      the Foley group. Patient charges were 31% lower in the Foley group (P <.001).
      CONCLUSION: Use of the Foley catheter resulted in a higher postinduction Bishop
      score, a greater change in Bishop score, a shorter induction time, and lower
      patient charges than did intracervical prostaglandin E2 gel.

PMID- 9914579
TI  - Androgens in preeclampsia.
AB  - OBJECTIVE: The purpose of the study was to determine whether maternal serum
      levels of androgens, especially testosterone, are higher in patients with
      preeclampsia than in matched normotensive control subjects. STUDY DESIGN: Serum
      testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and
      estradiol levels were measured in 16 subjects in the third trimester of pregnancy
      with documented preeclampsia and 26 healthy, normotensive women with similar
      maternal and gestational ages. All subjects were primigravid women with singleton
      pregnancies who were seen in the labor and delivery department at North Oakland
      Medical Centers in Pontiac, Mich. RESULTS: Total testosterone and free
      testosterone levels were significantly higher in patients with preeclampsia
      (213.6 +/- 25.9 ng/dL and 0.5 +/- 0.1 ng/dL, respectively) than in the control
      group (154.5 +/- 14.8 ng/dL and 0. 3 +/- 0.03 ng/dL, respectively). There were no
      significant differences in sex hormone binding globulin, dehydroepiandrosterone
      sulfate, and estradiol concentrations. There were also no significant differences
      in maternal age, gestational age, body mass index, and neonatal sex. CONCLUSION:
      Levels of the potent androgen testosterone were significantly higher in
      primigravid women with preeclampsia than in normotensive women with similar
      gestational and maternal ages. This difference may indicate a role for
      testosterone in the pathogenesis of preeclampsia.

PMID- 9914580
TI  - Favorable response of Eisenmenger syndrome to inhaled nitric oxide during
      pregnancy.
AB  - OBJECTIVE: Our goal was to evaluate the effectiveness of therapy with a specific
      pulmonary vasodilator, nitric oxide, in a woman with Eisenmenger syndrome during
      pregnancy. STUDY DESIGN: Eisenmenger syndrome consists of a congenital
      communication between the systemic and pulmonary circulation with secondary
      pulmonary hypertension causing reversal of flow through the shunt. Maternal
      morbidity is approximately 50% with the greatest risk of death being in the
      peripartum period. Pharmacologic therapy to relieve worsening pulmonary
      hypertension is confounded by the undesired effects of vasodilators on the
      systemic circulation. Therapy with a specific pulmonary vasodilator, nitric
      oxide, was attempted. RESULTS: A 27-year-old woman with Eisenmenger syndrome at
      36 weeks' gestation was treated with inhaled nitric oxide during the second stage
      of labor and the postpartum period when she experienced progressive refractory
      hypoxemia. Administration of nitric oxide was followed by improved oxygenation
      and lowering of pulmonary artery pressures. A brief episode of methemoglobinemia
      responded to lowering of the nitric oxide concentration and administration of
      intravenous methylene blue. Nitric oxide was discontinued after 48 hours. The
      patient died 2 days later despite continued vasodilator therapy including intra
      pulmonary artery prostacyclin. CONCLUSION: Inhaled nitric oxide can be used to
      correct the hypoxemia of Eisenmenger syndrome. Nitric oxide inhalation is easily
      performed, and pulmonary vasodilatory effects commence within minutes after
      administration.

PMID- 9914581
TI  - The role of soluble adhesion molecules in evaluating endothelial cell activation
      in preeclampsia.
AB  - OBJECTIVE: Adhesion molecules, such as vascular cell adhesion molecule 1, are
      known to be increased in the serum of patients with preeclampsia, indicating that
      these molecules are possible markers of endothelial cell activation. We
      investigated the influence of serum from women with preeclampsia on the
      expression of adhesion molecules by cultured endothelial cells. STUDY DESIGN:
      Human umbilical vein endothelial cells were cultured in Ham/Iscove modified
      Dulbecco's medium containing 20% pooled human serum, l -glutamine (200 mmol/L),
      penicillin, and streptomycin. We stimulated these cells for 24 hours with sera
      from patients with preeclampsia and then determined the levels of vascular cell
      adhesion molecule 1, intercellular cell adhesion molecule 1, E-selectin, and P
      selectin in the supernatant and in the maternal serum by means of enzyme-linked
      immunosorbent assay. These results were compared with those of sera obtained from
      normotensive pregnant and nonpregnant women. In addition, the expressions of
      these adhesion molecules on the endothelial surface were determined by immunofluo
      rescence microscopy. RESULTS: Only for vascular cell adhesion molecule 1 and E
      selectin were elevated plasma levels found in hypertensive patients, whereas
      intercellular cell adhesion molecule 1 and P-selectin showed similar plasma
      levels in all the patients. No differences in the levels of the adhesion
      molecules were found between the supernatants of endothelial cell cultures after
      stimulation with sera from patients with preeclampsia and those after stimulation
      with normotensive control sera. In contrast, with immunofluorescence microscopy
      we could detect higher amounts of vascular cell adhesion molecule 1,
      intercellular cell adhesion molecule 1, and E-selectin on the endothelial surface
      after stimulation with sera from women with preeclampsia. CONCLUSION: Although
      vascular cell adhesion molecule 1 and E-selectin were elevated in maternal serum
      samples from women with preeclampsia and on the endothelial surface after
      stimulation with such sera, there were no detectable increases in the levels of
      both of these adhesion molecules in the supernatant of cultured endothelial
      cells. We therefore assume that sera from women with preeclampsia may cause
      endothelial cell activation. Because we could not detect elevated concentrations
      of any of the investigated adhesion molecules in the supernatant of endothelial
      cells, we believe that factors other than sera from women with preeclampsia seem
      to play a major role in the release of soluble forms of adhesion molecules from
      the endothelial membrane.

PMID- 9914582
TI  - The prediction of fetal acidosis by means of intrapartum fetal pulse oximetry.
AB  - OBJECTIVES: The study's objectives were to verify a threshold value for fetal
      arterial oxygen saturation as the critical boundary for fetal compromise during
      labor and to investigate a method of predicting acidosis caused by hypoxemia.
      STUDY DESIGN: In a multicenter study involving 3 German obstetric centers, a
      total of 400 deliveries were monitored by fetal pulse oximetry (Nellcor-Puritan
      Bennett Model N-400 Oxygen Saturation Monitor and FS-14 Sensor; Nellcor, Inc,
      Pleasanton, Calif). The durations of low (</=30%), medium (31%-60%), and high
      (>60%) fetal arterial oxygen saturations during the measurement were compared
      between neonates with a pH <7.15 versus >/=7.15 and a base excess <-12 mmol/L
      versus >-12 mmol/L in the umbilical artery post partum and in neonates with an
      Apgar score <7 versus >/=7 by Mann-Whitney U test. In 121 of the pulse oximetry
      measurements the durations of low, medium, and high fetal arterial oxygen
      saturations were measured from one fetal scalp blood sampling to the next and
      correlated with the change of scalp blood pH between samplings. Multiple
      regression analysis was performed to estimate the expected change of pH between 2
      fetal scalp blood samplings, and receiver operating characteristic analysis was
      done to define a minimum duration of low fetal arterial oxygen saturation values
      to exclude or predict a significant decline of pH. RESULTS: Neonates with a 1
      minute Apgar score <7 differed from those with 1-minute Apgar score >/=7
      significantly in the duration of low fetal arterial oxygen saturation but not in
      the durations of medium and high fetal arterial oxygen saturations. The duration
      of low fetal arterial oxygen saturation had been significantly longer in children
      with pH <7.15 or base excess <-12 mmol/L in the umbilical artery compared with
      those with a pH >/=7.15 or base excess >/=-12 mmol/L. The duration of high fetal
      arterial oxygen saturation was significantly shorter for children with a pH <7.15
      or base excess <12 mmol/L than for those with a pH >/=7.15 or base excess >/=12
      mmol/L. There was no difference in the groups with respect to the duration of
      medium fetal arterial oxygen saturation values. The duration of low fetal
      arterial oxygen saturation proved to be the best predictor of a decline of scalp
      pH between 2 fetal scalp blood samples. The pH declined significantly with a
      longer duration of low fetal arterial oxygen saturation (0.02 per 10 minutes). No
      decrease of pH by more than 0.05 was observed unless fetal arterial oxygen
      saturation had remained at </=30% for >/=10 minutes. CONCLUSION: An arterial
      oxygen saturation of 30% was confirmed as the critical boundary for fetal
      compromise during labor. The development of acidosis seems to be predictable by
      the duration of hypoxemia, as indicated by fetal arterial oxygen saturation
      </=30%.

PMID- 9914583
TI  - Maternal 1-deamino-8-D-arginine-vasopressin-induced sequential decreases in
      plasma sodium concentration: ovine fetal renal responses.
AB  - OBJECTIVE: Acute maternal plasma hypotonicity induces a reduced placental osmotic
      gradient that contributes to augmented maternal-to-fetal water flow.
      Subsequently, maternal plasma hyponatremia results in fetal plasma hyponatremia,
      increased fetal urinary flow, and ultimately increased amniotic fluid volume. We
      hypothesized that both the degree of reduction in the placental osmotic gradient
      and the degree of fetal plasma hyponatremia influence fetal urinary diuretic
      responses. To differentiate the roles of these factors, we determined fetal
      urinary responses to graded levels of plasma hyponatremia during a constant
      placental osmotic gradient. Furthermore, we sought to establish the minimum level
      of plasma hyponatremia necessary to facilitate an increase in fetal urine
      production. STUDY DESIGN: Seven pregnant ewes (130 +/- 2 days) were prepared with
      maternal and fetal vascular catheters and a fetal bladder catheter. After 6 days
      of recovery, fetal urinary flow and urine and plasma compositions were measured
      during a 2-hour control period. At 2 hours, tap water (2 L, 38 degreesC) with a
      20-g bolus of 1-deamino-8-d-arginine-vasopressin was administered to the ewe.
      Maternal plasma sodium concentration was decreased from control by 5 to 7, 10 to
      12, and 15 to 17 mEq/L, and held at each level (levels 1, 2, and 3) for 60
      minutes. RESULTS: 1-Deamino-8-d-arginine-vasopressin administration induced
      sequential decreases in maternal and fetal plasma sodium concentrations (control
      146.9 +/- 0.5 mEq/L and 141.0 +/- 0.5 mEq/L, respectively) at level 1 (140.1 +/-
      0.6 mEq/L and 136.7 +/- 0.7 mEq/L, respectively), level 2 (132.5 +/- 0.7 mEq/L
      and 130.6 +/- 1.1 mEq/L, respectively), and level 3 (125.4 +/- 1.2 mEq/L and
      123.0 +/- 1.5 mEq/L, respectively). The maternal-fetal placental osmolality and
      sodium gradients were constant at each hypotonicity level. Fetal urinary flow
      significantly increased in association with the degree of hyponatremia (from 0.17
      +/- 0.03 mL/kg/min to 0. 26 +/- 0.04 mL/kg/min, 0.33 +/- 0.05 mL/kg/min, and 0.38
      +/- 00.5 mL/kg/min at levels 1, 2, and 3, respectively). CONCLUSIONS: These
      results indicate the following: (1) Sequential decreases in maternal plasma
      tonicity result in parallel decreases in fetal plasma tonicity. (2) The fetal
      urinary diuretic response is highly correlated with the degree of fetal plasma
      hypotonicity, despite a constant placental osmotic gradient. A fetal therapeutic
      response (53% increase in fetal urine production) may be induced by a maternal
      plasma sodium concentration decrease of only 5 to 7 mEq/L.

PMID- 9914584
TI  - Neonatal behavioral profile of the offspring of women who continued to exercise
      regularly throughout pregnancy.
AB  - OBJECTIVE: The objective of the study was to test the hypothesis that continuing
      regular exercise throughout pregnancy alters early neonatal behavior. STUDY
      DESIGN: The offspring of 34 women who exercised were compared with those of 31
      demographically similar control subjects. All women had normal antenatal courses.
      Behavior was assessed at 5 days after birth with the Brazelton Scales. RESULTS:
      The offspring of the exercising women performed better in 2 of the 6 behavioral
      constellations when examined at 5 days after birth. The scores reflecting their
      ability to orient to environmental stimuli were (mean +/- SEM) 7.6 +/- 0.1 and
      6.5 +/- 0. 3, respectively, and the scores reflecting their ability to regulate
      their state or quiet themselves after sound and light stimuli were 6. 6 +/- 0.2
      and 4.9 +/- 0.3, respectively. The scores reflecting habituation (7.9 +/- 0.2 and
      8.0 +/- 0.1, respectively), motor organization (5.7 +/- 0.1 and 5.5 +/- 0.1,
      respectively), autonomic stability (5.9 +/- 0.2 and 5.5 +/- 0.3, respectively),
      and behavioral state range (4.1 +/- 0.2 and 4.5 +/- 0.3, respectively) were not
      significantly different. CONCLUSIONS: These data indicate that the neonates born
      of exercising mothers have a different neurobehavioral profile as early as the
      fifth day after birth.

PMID- 9914585
TI  - Angiotensinogen Thr235 variant is associated with abnormal physiologic change of
      the uterine spiral arteries in first-trimester decidua.
AB  - OBJECTIVE: The angiotensinogen Thr235 polymorphism associated with preeclampsia
      is tightly linked to a mutation in the angiotensinogen promoter A(-6), which may
      lead to elevated expression in decidual spiral arteries. We hypothesize that
      locally elevated angiotensin II levels play a role in failed physiologic change
      leading to preeclampsia. Our objective was to determine whether spiral artery
      morphologic characteristics were different in first-trimester decidual samples
      from women homozygous for the angiotensinogen Thr235 allele and women homozygous
      for the normal angiotensinogen Met235 allele. STUDY DESIGN: We used quantitative
      histologic analysis to study 1266 spiral artery cross-sections in decidual
      samples obtained from normal pregnancies (n = 53) terminated at 8 weeks'
      gestation. To define vessel characteristics before pregnancy-induced remodeling,
      we also examined 60 arteries in nonpregnant endometrial control samples (n = 5).
      We measured the aspect ratio, media area, and external diameter of each cross
      section with Image-Pro plus software. Maternal angiotensinogen genotypes were
      determined by means of mutagenically separated polymerase chain reaction. Average
      spiral artery morphologic measurements were compared between genotypes with the
      Student t test. RESULTS: The media area/external diameter ratio was lower in
      decidual samples than in endometrial samples (P <.0001), consistent with
      pregnancy-induced physiologic changes. Women homozygous for the angiotensinogen
      Thr235 allele (n = 11) had a greater area/diameter ratio than did women
      homozygous for the normal angiotensinogen Met235 allele (n = 11, P <.05). Samples
      from heterozygous women (n = 31) had intermediate values. CONCLUSION: Our results
      suggest that the angiotensinogen Thr235 allele predisposes women toward abnormal
      physiologic change, potentially beginning the cascade of events leading to
      preeclampsia.

PMID- 9914586
TI  - Expression of prostaglandin H synthase isoforms in human myometrium at
      parturition.
AB  - OBJECTIVE: The purpose of this study was to identify the isoforms and splicing
      patterns of prostaglandin H synthase present in pregnant human lower-segment
      myometrium and determine whether there is differential expression of the isoforms
      or splice variants with respect to gestational age or parturition. STUDY DESIGN:
      Lower-segment myometrium was collected at cesarean section at term (>37 weeks) or
      preterm (<37 weeks) from patients who were or were not in labor. Total messenger
      ribonucleic acid was isolated and reverse transcribed. Polymerase chain reaction
      for prostaglandin H synthase isoforms 1 and 2 and calponin were performed.
      Primers designed to characterize the splicing patterns of exon 9 of prostaglandin
      H synthase-1 were used. RESULTS: The predominant polymerase chain reaction
      product in all samples corresponds to prostaglandin H synthase-1 messenger
      ribonucleic acid spliced to include exon 9, but a less-abundant polymerase chain
      reaction product corresponding to prostaglandin H synthase-1 messenger
      ribonucleic acid spliced at the internal donor site of exon 9 was also detected.
      Prostaglandin H synthase-2 messenger ribonucleic acid was detected in human
      myometrium at a lower abundance than prostaglandin H synthase-1, and neither
      prostaglandin H synthase-1 or prostaglandin H synthase-2 messenger ribonucleic
      acid expression changed significantly with gestational age or labor. CONCLUSION:
      Both prostaglandin H synthase-1 and prostaglandin H synthase-2 isoforms are
      present in human myometrium. The prostaglandin H synthase-1 messenger ribonucleic
      acid that includes all of exon 9 encodes the predominant prostaglandin H synthase
      1 isoform present in human myometrium. No significant alterations in the
      expression or splicing patterns for prostaglandin H synthase-1 were detected with
      respect to gestational age or the onset of labor; but prostaglandin H synthase-1
      expression appeared higher at term in anticipation of labor. Although
      prostaglandin H synthase-2 is present in human myometrium, induction of
      prostaglandin H synthase-2 does not occur in lower-segment myometrium at
      parturition.

PMID- 9914587
TI  - Pregnancy in von Hippel-Lindau disease.
AB  - We retrospectively evaluated maternal and fetal outcomes in a series of women
      with von Hippel-Lindau disease. Data resulted from 56 pregnancies in 30 women.
      Symptoms related to von Hippel-Lindau disease occurred in 3 of 56 pregnancies. In
      this unselected group of patients with von Hippel-Lindau disease, most
      pregnancies had a favorable outcome with a 96.4% survival rate for fetuses and a
      5.4 % von Hippel-Lindau-specific morbidity rate in the mothers.

PMID- 9914588
TI  - Pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate
      diphosphohydrolase to products of activated polymorphonuclear leukocytes.
AB  - To test the hypothesis that pregnancy enhances the sensitivity of glomerular ecto
      adenosine triphosphate-diphosphohydrolase to products of activated
      polymorphonuclear leukocytes, cryostat-cut kidney sections of pregnant and
      cycling rats were exposed to activated polymorphonuclear leukocytes and
      subsequently stained for ecto-adenosine triphosphate-diphosphohydrolase activity.
      The results show that the levels of ecto-adenosine triphosphate
      diphosphohydrolase activity of pregnant rats showed a significantly greater
      decrease after incubation with activated polymorphonuclear leukocytes than did
      those of cycling rats.

PMID- 9914589
TI  - Repeated antenatal corticosteroids: size at birth and subsequent development.
AB  - OBJECTIVE: The objective was to study the effects of repeated antenatal
      corticosteroids on birth size, growth, and development in preterm infants. STUDY
      DESIGN: This observational study followed up for 3 years a prospective geographic
      cohort in the state of Western Australia of 477 singleton infants born at <33
      weeks' gestation. RESULTS: Birth weight ratio decreased with increasing number of
      corticosteroid courses (P =.001), and multivariate analyses confirmed a reduction
      in birth weight of as much as 9% (P =.014) and a reduction in head circumference
      of as much as 4% (P =.0024). There were no additional benefits in mortality or
      respiratory outcomes, and there was a trend toward more severe chronic lung
      disease. At age 3 years growth and severe disability outcomes did not appear to
      be related to increasing number of corticosteroid courses. CONCLUSIONS: In this
      cohort study repeated corticosteroid courses were associated with adverse effects
      on size at birth without apparent benefits. These changes have the potential to
      affect later development.

PMID- 9914590
TI  - Maternal cardiac troponin I levels during normal labor and delivery.
AB  - OBJECTIVE: Diagnosis of myocardial infarction in pregnant women on the basis of
      changes in biochemical markers is complicated by the release of some of these
      markers from noncardiac tissue sources. We compared troponin I levels with those
      of other markers in normal pregnant women. STUDY DESIGN: In 51 healthy women at
      term in labor, cardiac troponin I, myoglobin, creatine kinase, and creatine
      kinase MB levels were determined at admission, during the second stage of labor,
      and within 30 minutes, 12 hours, and 24 hours after delivery. RESULTS: Mean
      admission levels for all markers were below the upper limit of normal. Mean
      concentrations of myoglobin, creatine kinase, and creatine kinase MB mass were
      increased nearly twofold within 30 minutes after delivery. The highest level of
      troponin I (0.134 ng/mL) at all time points was below the cutoff value (0.15
      ng/mL) for discriminating myocardial infarction. CONCLUSIONS: Because only
      troponin I levels remained undetectable during and after delivery, it is
      potentially the most useful biochemical marker for monitoring pregnant women for
      myocardial injury.

PMID- 9914591
TI  - Reproductive hormones and aminoterminal propeptide of type III procollagen in
      serum as early markers of pelvic pain during late pregnancy.
AB  - OBJECTIVE: The object was to study serum concentrations of reproductive hormones
      and aminoterminal propeptide of type III procollagen in early pregnancy as
      markers of pelvic pain (sacral pain or symphyseal pain) during later pregnancy.
      STUDY DESIGN: A prospective, clinical cohort study was performed, with repeated
      examinations of 200 women. RESULTS: Serum concentrations of relaxin and serum
      concentrations of propeptide of type III procollagen (a collagen turnover marker)
      measured in early pregnancy were significantly correlated with pelvic pain with
      onset during pregnancy and reported in late pregnancy (positively and negatively,
      respectively). In a multivariate analysis, relaxin and propeptide of type III
      procollagen concentrations remained independently and significantly correlated
      with pelvic pain. CONCLUSION: Serum concentrations of relaxin and propeptide of
      type III procollagen measured in early pregnancy may reflect the cause of and
      indicate an increased risk of pelvic pain (back pain or symphyseal pain) during
      late pregnancy. The mechanism is unclear.

PMID- 9914592
TI  - Effect of aspirin in pregnant women is dependent on increase in bleeding time.
AB  - OBJECTIVES: Randomized trials with low-dose aspirin to prevent preeclampsia and
      intrauterine growth restriction have yielded conflicting results. In particular,
      3 recent large trials were not conclusive. Study designs, however, varied greatly
      regarding selection of patients, dose of aspirin, and timing of treatment, all of
      which can be determinants of the results. Retrospectively analyzing the
      conditions associated with failure or success of aspirin may therefore help to
      draw up new hypotheses and prepare for more specific randomized trials. STUDY
      DESIGN: We studied a historical cohort of 187 pregnant women who were considered
      at high risk for preeclampsia, intrauterine growth restriction, or both and were
      therefore treated with low-dose aspirin between 1989 and 1994. Various
      epidemiologic, clinical, and laboratory data were extracted from the files.
      Univariate and multivariate analyses were performed to search for independent
      parameters associated with the outcome of pregnancy. RESULTS: Age, parity,
      weight, height, and race had no influence on the outcome. The success rate was
      higher when treatment was given because of previous poor pregnancy outcomes than
      when it was given for other indications, and the patients with successful therapy
      had started aspirin earlier than had those with therapy failure (17.7 vs 20.0
      weeks' gestation, P =.04). After multivariate analysis an increase in Ivy
      bleeding time after 10 days of treatment by >2 minutes was an independent
      predictor of a better outcome (odds ratio 0.22, 95% confidence interval 0.09
      0.51). Borderline statistical significance was observed for aspirin initiation
      before 17 weeks' gestation (odds ratio 0.44, 95% confidence interval 0.18-1. 08).
      Abnormal uterine artery Doppler velocimetric scan at 20-24 weeks' gestation (odds
      ratio 3.31, 95% confidence interval 1.41-7.7), abnormal umbilical artery Doppler
      velocimetric scan after 26 weeks' gestation (odds ratio 37.6, 95% confidence
      interval 3.96-357), and use of antihypertensive therapy (odds ratio 6.06, 95%
      confidence interval 2.45-15) were independent predictors of poor outcome.
      CONCLUSIONS: Efficacy of aspirin seems optimal when bleeding time increases >/=2
      minutes with treatment, indicating a more powerful antiplatelet effect. This
      suggests that the dose of aspirin should be adjusted according to a biologic
      marker of the antiplatelet effect. A prospective trial is warranted to test this
      hypothesis.

PMID- 9914593
TI  - Urinary trypsin inhibitor levels in amniotic fluid of normal human pregnancy:
      decreased levels observed at parturition.
AB  - OBJECTIVE: Urinary trypsin inhibitor, a light chain of inter-alpha-trypsin
      inhibitor, is reported to inhibit uterine contractility during pregnancy. The
      objective was to measure amniotic fluid urinary trypsin inhibitor levels in women
      throughout pregnancy. STUDY DESIGN: We determined levels of urinary trypsin
      inhibitor in human amniotic fluid (n = 40) by means of Western blot analysis. For
      quantification, computerized scanning and densitometry were used. Results were
      analyzed for statistical significance with the Mann-Whitney U test. RESULTS:
      During pregnancy, mean amniotic fluid urinary trypsin inhibitor levels (+/-SD)
      were 1.5 +/- 0.22, 1. 2 +/- 0.18, and 0.58 +/- 0.24 micromol/L at 15 to 22 (n =
      10), 30 to 35 (n = 5), and 37 to 40 (n = 10) weeks' gestation, respectively.
      There was a significant negative correlation of urinary trypsin inhibitor level
      with gestational age. A significant difference was observed in amniotic fluid
      urinary trypsin inhibitor levels before and after (0.10 +/- 0.03 micromol/L; n =
      15) the onset of labor. CONCLUSION: Amniotic fluid urinary trypsin inhibitor
      levels decrease significantly at term. These results support the hypothesis that
      parturition may occur through the down-regulation of urinary trypsin inhibitor,
      which may decrease uterine contractility and maintain the uterus in a state of
      quiescence during pregnancy.

PMID- 9914594
TI  - Prenatal ultrasonographic prediction of homozygous type 1 alpha-thalassemia at 12
      to 13 weeks of gestation.
AB  - We determined the feasibility of prenatal prediction of type 1 homozygous alpha
      thalassemia at 12 to 13 weeks of gestation by either abdominal or vaginal (or
      both) ultrasonographic examination to measure the fetal cardiothoracic ratio in
      135 at-risk pregnancies. Forty-three fetuses were affected by homozygous type 1
      alpha-thalassemia. The mean cardiothoracic ratio was significantly larger than
      that of the unaffected fetuses (0.54 vs 0.45, P <.0005), with no overlap between
      the 2 groups. A cardiothoracic ratio cutoff point of >/=0.5 was 100% sensitive
      and specific for disease.

PMID- 9914595
TI  - The clinical significance of intermittent sinusoidal fetal heart rate.
AB  - Sinusoidal fetal heart rate may have a spectrum of occurrence that indicates
      degree of fetal morbidity. Twelve cases of intermittent sinusoidal fetal heart
      rate were reviewed for fetal outcome. Findings of anemia, low umbilical cord pH,
      and large base excess support that intermittent sinusoidal fetal heart rate may
      be an early indicator of impending fetal compromise.

PMID- 9914596
TI  - Endoscopic coverage of fetal myelomeningocele in utero.
AB  - OBJECTIVE: Our goal was to evaluate the safety and efficacy of minimally invasive
      surgery for the coverage of myelomeningocele in utero. STUDY DESIGN: Women in the
      mid-second trimester of a pregnancy complicated by fetal myelomeningocele were
      offered an experimental procedure designed to prevent ongoing exposure of the
      spinal cord to the intrauterine environment. The procedure consisted of maternal
      laparotomy while the patient was under both general and epidural anesthesia, with
      exposure of the gravid uterus. Endoscopic ports were placed for camera and
      operating instruments. Amniotic fluid was removed and replaced with carbon
      dioxide. The fetus was then positioned and a maternal split-thickness skin graft
      was placed over the exposed spinal cord or neural elements. The skin graft and a
      covering of Surgicel Absorbable Hemostat were attached with fibrin glue prepared
      from autologous cryoprecipitate. RESULTS: Four fetuses with open myelomeningocele
      underwent endoscopic coverage of the spinal lesion between 22 weeks 3 days and 24
      weeks 3 days of gestation. One infant, delivered by planned cesarean section at
      35 weeks' gestation after demonstration of fetal lung maturity, is almost 3 years
      old. A second infant was delivered by cesarean section at 28 weeks after preterm
      labor and is now almost 6 months old. Both survivors manifest only mild motor and
      somatosensory deficits. One fetus who was delivered 1 week after operation after
      development of amnionitis died in the delivery room of extreme prematurity. The
      final fetus died intraoperatively from abruptio placentae. CONCLUSION: Minimally
      invasive fetal surgery appears to constitute a feasible approach to nonlethal
      fetal malformations that result in progressive and disabling organ damage.

PMID- 9914598
TI  - Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes.
AB  - OBJECTIVE: Altered transport functions in the placenta might contribute to
      adverse outcome of pregnancies in women with diabetes. Therefore we studied
      placental glucose transport in this pregnancy complication. STUDY DESIGN:
      Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles
      were isolated from women with uneventful pregnancies (control subjects, n = 21)
      and from women with pregnancies complicated by insulin-dependent diabetes
      mellitus, White class D (n = 7). Glucose uptake and GLUT 1 (glucose transporter
      1) expression were studied by means of radiolabeled tracers and Western blot,
      respectively. RESULTS: In the group with insulin-dependent diabetes mellitus,
      values for hemoglobin A1c were moderately elevated in the first trimester (6.61
      +/- 0.35) but not later in pregnancy and 4 of the 7 neonates were large for
      gestational age. In the basal membrane vesicles, insulin-dependent diabetes
      mellitus was associated with a 40% increase in GLUT 1 expression and a 59% higher
      mediated uptake of d -glucose. No alterations could be demonstrated in
      microvillus membrane vesicles. CONCLUSION: Placental glucose transport capacity
      appears to be increased in insulin-dependent diabetes mellitus. These alterations
      might explain the occurrence of macrosomia despite well-controlled diabetes.

PMID- 9914597
TI  - Measurement of obstetric conjugate by ultrasonic tomography and its significance.
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical usefulness
      of the measurement of ultrasonic obstetric conjugate. STUDY DESIGN: In 209
      pregnant women, ultrasonic obstetric conjugate was measured twice at 28 and 36
      weeks of pregnancy. In 26 of these patients the measurement of obstetric
      conjugate by x-ray pelvimetry was also performed at 36 weeks of pregnancy because
      of medical indications. Obstetric outcome was investigated in association with
      ultrasonic obstetric conjugate. The relationship between ultrasonic obstetric
      conjugate and x-ray pelvimetry was investigated. RESULTS: Ultrasonic obstetric
      conjugate ranged from 10.7 to 15.1 cm. In 12 patients (5.7%) ultrasonic obstetric
      conjugate was less than 12 cm. Six of them (50.0%) underwent cesarean section
      because of dystocia. This percentage was significantly higher than 7.1% of the
      cesarean section rate (14 of 197) in patients with ultrasonic obstetric conjugate
      more than 12 cm (P <.001). A close positive correlation was observed between
      ultrasonic obstetric conjugate and x-ray pelvimetry (r = 0.91; P <.0001).
      CONCLUSIONS: We conclude that ultrasonic obstetric conjugate measurement is a
      safe and useful procedure in the prediction of dystocia.

PMID- 9914599
TI  - A high-sensitivity alternative to "routine" genetic amniocentesis: multiple
      urinary analytes, nuchal thickness, and age.
AB  - OBJECTIVE: Our purpose was to evaluate the Down syndrome screening efficiency of
      a new algorithm consisting of multiple urinary biochemical and ultrasound markers
      for use in high-risk groups such as women of advanced maternal age. STUDY DESIGN:
      The urinary beta-core fragment of human chorionic gonadotropin (beta-core
      fragment) and total urinary estriol, along with fetal nuchal thickness, were
      measured prospectively in pregnant women who were undergoing genetic
      amniocentesis at midtrimester (15 to 24 weeks). The most common indication for
      amniocentesis was advanced maternal age (90.2%). An analyte ratio (beta-core
      fragment/total estriol ratio) was developed. The values were expressed as
      multiples of the normal median. An increase in the observed nuchal thickness
      (delta nuchal thickness) above that expected on the basis of the biparietal
      diameter was calculated. On the basis of the mean and standard deviations of the
      urinary analyte ratio in normal fetuses and also Down syndrome, we calculated
      individual Down syndrome likelihood ratios for each of the two parameters, using
      gaussian analysis. The product of the likelihood ratios, based on delta nuchal
      thickness and urinary beta-core fragment-total estriol values times the maternal
      age-related risk, gave the overall Down syndrome risk. The screening efficiency
      of our algorithm at various risk thresholds was determined. RESULTS: There were
      13 (2.8%) cases of Down syndrome in a total study population of 457. At a risk
      threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of
      4.5%. Corresponding values at a risk threshold of >1 in 78 were a sensitivity of
      100% with a false-positive rate of 5.2%. CONCLUSION: By combining urinary
      analyte, nuchal thickness, and maternal age data, we achieved a high Down
      syndrome detection rate with a low false-positive rate. This algorithm would be
      attractive as an alternative to "routine" amniocentesis based solely on advanced
      maternal age. The potential benefits of this protocol could include a significant
      reduction in the rate of amniocentesis, along with substantial savings in medical
      expenditures.

PMID- 9914600
TI  - Placental transfer of sulindac, sulindac sulfide, and indomethacin in a human
      placental perfusion model.
AB  - OBJECTIVE: Evaluation of the transplacental transfer and placental metabolism of
      sulindac, its active sulfide metabolite, and indomethacin, drugs used as
      tocolytic agents, in dual recirculating human placental perfusion. STUDY DESIGN:
      Term placentas were obtained with maternal consent immediately after delivery.
      Drugs were added to the maternal reservoir, together with antipyrine as a
      reference compound, and disappearance from the maternal circulation and
      appearance in the fetal circulation were followed up for 2 hours in 4 experiments
      for each compound. Drug concentrations were analyzed by high-performance liquid
      chromatography. RESULTS: The fetal/maternal concentration ratios after 2-hour
      perfusions were 0. 34 +/- 0.19 (mean +/- SD, sulindac), 0.54 +/- 0.17 (sulfide),
      and 0. 45 +/- 0.16 (indomethacin), and the fetal-maternal transfer percentages at
      2 hours were 11.6 +/- 5.9 (sulindac), 18.2 +/- 5.2 (sulfide), and 15.3 +/- 4.5
      (indomethacin). No metabolism of sulindac or indomethacin was detected.
      CONCLUSION: Sulindac sulfide, formed through hepatic metabolism, reaches the
      fetus in higher concentrations than does sulindac or indomethacin. Neither
      sulindac nor indomethacin is metabolized by the human placenta.

PMID- 9914601
TI  - Fetal heart rate patterns in term labor vary with sex, gestational age, epidural
      analgesia, and fetal weight.
AB  - OBJECTIVES: Our purpose was to analyze the previously unreported effect of fetal
      sex on the fetal heart rate in labor and to measure its magnitude in relation to
      the effects of other independent clinical variables. STUDY DESIGN: The last hour
      of the intrapartum heart rates of 1884 term singleton fetuses collected during
      routine clinical monitoring over 19 months in Oxford, United Kingdom, was
      analyzed by computerized techniques. The records were selected for completeness
      and continuity until within at least 30 minutes of delivery. A subset of records
      from earlier in labor and a separate archive of antepartum normal term records
      were also examined. RESULTS: Female fetuses had significantly faster heart rates
      than male fetuses (P <.0001). Epidural analgesia, weight percentile (adjusted for
      age and sex), parity, the duration of first and second stages of labor, and a
      fall in umbilical arterial blood pH at birth also independently modulated the
      fetal heart rate (all P <.0001). The effects of these independent variables on
      heart rate were additive, the most important being epidural analgesia as a cause
      of tachycardia. The effect of fetal sex was less in the first stage, 6 to 7 hours
      before delivery, and was not present before the onset of labor (in another 552
      pregnancies at 37 to 38 weeks). CONCLUSIONS: The fetal heart rate response of
      female fetuses to normal labor differs from that of male fetuses. Computerized
      numeric analysis of intrapartum fetal heart rate patterns will need to take into
      account the multiple factors that influence the fetal heart rate to identify
      precisely which patterns predict clinical outcome.

PMID- 9914602
TI  - Lipoic acid prevention of neural tube defects in offspring of rats with
      streptozocin-induced diabetes.
AB  - OBJECTIVE: Increased oxidant stress has been suggested to play a role in the
      pathogenesis of disturbed embryogenesis in diabetic pregnancies. The present
      study was conducted to determine whether administration of lipoic acid, a
      naturally occurring antioxidant, would reduce the incidence of diabetic
      embryopathy in the streptozocin-induced diabetic rat model. STUDY DESIGN: After
      conception, rats were randomly distributed to 5 groups. From day 1, rats were
      daily injected intraperitoneally with either lipoic acid, 30 mg/kg, or vehicle.
      At day 6, rats from groups 3, 4, and 5 were made diabetic by a single
      intraperitoneal injection of streptozocin. Group 4 rats were injected with lipoic
      acid from day 1 to day 6, after vehicle treatment until day 17. At day 17 of
      gestation, rats were killed. The fetuses were released from the yolk sacs and
      surrounding decidua and were examined for size, resorption rate, and neural tube
      defects. RESULTS: Pregnant diabetic rats treated with vehicle lost weight during
      pregnancy (-3.2 +/- 1.9 g/d), as opposed to normal pregnancy-related weight gain
      (3.5 +/- 0.5 g/d). Treatment with lipoic acid protected against diabetes-induced
      weight loss, without a measurable effect on fed-state glucose concentrations.
      Daily treatment with lipoic acid (pregnancy days 1 to 17) was efficient in
      reducing the resorption rate from 24.0% +/- 9.5% in vehicle-treated diabetic rats
      to 10.2% +/- 4.8% in lipoic acid-treated diabetic rats (P <.05). The rate of
      neural tube defects in diabetic rats treated with lipoic acid throughout the
      pregnancy was reduced from 26.0% +/- 7.0% to 10.2% +/- 3.2% (P <.05). In rats
      treated only during pregnancy days 1 to 5 (before diabetes induction), lipoic
      acid failed to exert its protective effects against neural tube defects, which
      emphasizes the importance of the presence of lipoic acid during the organogenesis
      period. The atherosis of placental vasculature demonstrated in the vehicle
      treated diabetic rats was absent from placentas obtained from lipoic acid-treated
      diabetic animals. CONCLUSIONS: Our data demonstrate a protective effect of lipoic
      acid against diabetic embryopathy, fetal losses, and ultrastructural alteration
      of diabetic placentas.

PMID- 9914603
TI  - Increased midtrimester amniotic fluid activin A: a risk factor for subsequent
      fetal death.
AB  - OBJECTIVE: The objective of this study was to determine whether concentrations of
      activin A and corticotropin-releasing factor in amniotic fluid can identify
      patients at risk of fetal death. STUDY DESIGN: A retrospective case-control study
      of women who have had a midtrimester amniocentesis was designed. Case subjects
      consisted of patients who had a spontaneous fetal death after the procedure,
      whereas the control group consisted of patients who had a normal pregnancy
      outcome after midtrimester amniocentesis. Dimeric activin A was measured by a
      specific 2-site enzyme immunoassay, and corticotropin-releasing factor was
      measured by a specific and sensitive radioimmunoassay after acidic extraction.
      Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test,
      and chi2 tests and regression analysis. RESULTS: First, activin A was detectable
      in all amniotic fluid samples. Second, the concentration of activin A in amniotic
      fluid increased with advancing gestational age. Third, patients who subsequently
      had a fetal death had a higher median concentration of activin A than those with
      a normal pregnancy outcome (P <.01). Fourth, an amniotic fluid concentration of
      activin A greater than the 95th confidence interval for gestational age was found
      in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P
      <.005). Finally, the median concentration of corticotropin-releasing factor in
      amniotic fluid was not different in case subjects and control subjects.
      CONCLUSIONS: An elevated concentration of activin A in amniotic fluid identifies
      women at risk of fetal death.

PMID- 9914604
TI  - In vitro models to predict the in vivo mechanism, rate, and extent of placental
      transfer of dideoxynucleoside drugs against human immunodeficiency virus.
AB  - OBJECTIVE: We tested the hypothesis that the mechanism, rate, and extent of in
      vivo placental transfer of dideoxynucleoside drugs against human immunodeficiency
      virus can be predicted by the in vitro perfused human placenta and the drug
      octanol-water partition coefficient. STUDY DESIGN: Near-term pregnant macaques
      (Macaca nemestrina ) underwent long-term catheterization for the administration
      of 4 dideoxynucleosides against human immunodeficiency virus: zidovudine,
      didanosine, zalcitabine, and stavudine. Maternal plasma, fetal plasma, and
      amniotic fluid concentrations were determined frequently after intravenous bolus
      and/or infusion of the drugs administered into the maternal or fetal circulation
      on separate occasions. Antipyrine was included in all experiments as a marker of
      placental blood flow. The mechanism, rate, and extent of placental transfer of
      the 4 dideoxynucleosides in perfused human placenta were determined and compared
      with the findings obtained by others. RESULTS: The mechanism and rate of the
      antipyrine-normalized placental transfer of the 4 dideoxynucleosides in perfused
      human placenta were highly correlated with those observed in vivo. The extent of
      placental transfer (fetal/maternal steady-state plasma concentration ratio) was
      also highly correlated with both the antipyrine-normalized placental transfer
      clearance (clearance index) determined in the in vitro perfused human placenta
      model (r 2 = 0.95, in vitro clearance-index model) and the drug octanol-water
      partition coefficient (r 2 = 0.99, in vitro partition-coefficient model). To
      determine the predictive capacity of these correlative models, we predicted the
      fetal/maternal steady-state plasma concentration ratio of each drug after
      excluding the data on that drug from the model fit. Both in vitro models to
      predict in vivo placental transfer of drug models resulted in good predictions of
      the observed fetal/maternal steady-state plasma concentration ratio (mean error:
      in vitro clearance-index model = -1. 2%; in vitro partition-coefficient model =
      3.9%). CONCLUSIONS: We propose that our models will accurately predict the extent
      of placental transfer of dideoxynucleoside drugs against human immunodeficiency
      virus. The models may also be applicable to other classes of drugs, regardless of
      therapeutic category, provided that these drugs passively diffuse across the
      placenta. Such a result will expedite phase 1 clinical trials of drugs in
      pregnant women.

PMID- 9914606
TI  - Correction of hemorrhage-induced anemia with intra-amniotic iron in the ovine
      fetus.
AB  - OBJECTIVE: This study tested the hypothesis that intra-amniotic iron treatment
      would enhance fetal red blood cell production after an acute, severe fetal
      hemorrhage of 40% of estimated blood volume over 2 hours. STUDY DESIGN: Three
      groups of late-gestation ovine fetuses were studied for 10 days: (1) control
      fetuses (n = 8), (2) fetuses hemorrhaged on day 3 (n = 11), and (3) similarly
      hemorrhaged fetuses supplemented with a single bolus of 60 mg of iron injected
      intra-amniotically immediately after the hemorrhage (n = 7). Statistical analysis
      was by 3-factor analysis of variance. RESULTS: At 24 hours after hemorrhage, red
      blood cell mass increased 5% in the control group and was reduced equally in both
      hemorrhage groups by 32% below day 3 prehemorrhage values. At 7 days after
      hemorrhage, red blood cell mass increased 27.8% +/- 2.6% (SE) above day 3
      baseline values in the control fetuses. In the nonsupplemented hemorrhaged
      fetuses, red blood cell mass was not different from prehemorrhage values after 7
      days (+3.7% +/- 4.1%), whereas red blood cell mass increased by 29.9% +/- 6.1%
      above prehemorrhage values in the iron-supplemented hemorrhage group (P <.001).
      CONCLUSION: Intra-amniotic iron supplementation resulted in full restoration of
      red blood cell mass within 7 days after a large loss of blood in fetal sheep,
      whereas restoration failed without iron supplementation. Intra-amniotic iron
      treatment may be of therapeutic value in restoring red blood cell mass in human
      fetuses with certain types of anemia such as that resulting from fetal or
      fetomaternal hemorrhage.

PMID- 9914605
TI  - Impact of pregnancy-induced hypertension on fetal growth.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of different
      types of pregnancy-induced hypertension on fetal growth. STUDY DESIGN: A
      retrospective cohort study was conducted on the basis of 16,936 births from
      January 1, 1989, through December 31, 1990, by means of data from a population
      based perinatal database in Suzhou, China. Pregnancy-induced hypertension was
      classified as gestational hypertension, preeclampsia, or severe preeclampsia
      eclampsia. Univariate and multivariate regression analyses were performed to
      examine the effect of the various types of pregnancy-induced hypertension on
      gestational age, preterm birth, birth weight, low birth weight, and intrauterine
      growth restriction. RESULTS: Gestation was 0.6 week shorter in women with severe
      preeclampsia than in normotensive women (P <.01). However, the risk of preterm
      birth was not increased with any classification of pregnancy-induced hypertension
      (for severe preeclampsia: adjusted odds ratio 1.75; 95% confidence interval, 0.88
      3.47). After adjustment for duration of gestation and other confounders,
      preeclampsia and severe preeclampsia increased the risk of intrauterine growth
      restriction and low birth weight. The adjusted odds ratios of low birth weight
      were 2.65 (1.73-4.39) for preeclampsia and 2.53 (1.19-4.93) for severe
      preeclampsia. However, the risk of low birth weight was not increased
      significantly for gestational hypertension (adjusted odds ratio 1.56 [1.00
      2.41]). CONCLUSION: Preeclampsia increases the risk of intrauterine growth
      restriction and low birth weight.

PMID- 9914607
TI  - Neonatal outcome in severe preeclampsia at 24 to 36 weeks' gestation: does the
      HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome
      matter?
AB  - OBJECTIVE: Our purpose was to compare neonatal outcome after preterm delivery of
      infants whose gestation was complicated by the HELLP (hemolysis, elevated liver
      enzymes, and low platelet count) syndrome, partial HELLP syndrome, or severe
      preeclampsia. STUDY DESIGN: We reviewed the maternal and neonatal charts from 269
      consecutive pregnancies complicated by the HELLP syndrome or severe preeclampsia
      managed at our perinatal center. The HELLP syndrome was defined by previously
      published laboratory criteria. Viable pregnancies were divided into 3 groups:
      HELLP syndrome, partial HELLP syndrome (at least 1, but not all 3, features of
      the HELLP syndrome), and severe preeclampsia (no features of the HELLP syndrome).
      Results were compared by means of chi2 analysis and Student t test where
      appropriate. Logistic regression was used to evaluate outcome variables at
      different gestational ages. RESULTS: There were no significant differences in
      complications among the 3 groups at each gestational age. There was, as expected,
      a significant decrease in morbidity and mortality rates with advanced gestational
      age. CONCLUSIONS: In severe preeclampsia, neonatal morbidity and death are
      related to gestational age rather than to the presence or absence of the HELLP
      syndrome. Whether expectant management is safe for women with the HELLP syndrome
      requires further study.

PMID- 9914608
TI  - Genetic amniocentesis after multifetal pregnancy reduction.
AB  - OBJECTIVE: Our purpose was to evaluate the pregnancy loss rate resulting from
      genetic amniocentesis after multifetal pregnancy reduction. STUDY DESIGN: A
      cohort study was performed in pregnancies with maternal age >30 years. Pregnancy
      loss in a study population of 127 patients who underwent genetic amniocentesis
      after multifetal pregnancy reduction were compared with a control group of 167
      patients who did not have genetic amniocentesis after multifetal pregnancy
      reduction. RESULTS: The pregnancy loss rate in patients who underwent genetic
      amniocentesis after multifetal pregnancy reduction was 3.1% (4/127 cases)
      compared with 7.2% (12/167 cases) in the controls (P >.05). In the study group
      evidence of infection was found in only 1 case, in which the pregnancy loss
      occurred 1 day after the amniocentesis. In the other cases the pregnancy losses
      occurred 5 weeks after genetic amniocentesis, and these losses could not be
      directly attributed to either genetic amniocentesis or the multifetal reduction
      procedure. CONCLUSION: Our data suggest that the performance of genetic
      amniocentesis after multifetal pregnancy reduction does not increase the risk of
      pregnancy loss over that observed in association with the reduction itself.

PMID- 9914609
TI  - The role of forceps rotation in maternal and neonatal injury.
AB  - OBJECTIVE: Our purpose was to assess the impact of forceps rotation on maternal
      and neonatal injury. STUDY DESIGN: In this retrospective case-controlled study
      performed at the University of Texas Medical Branch at Galveston all forceps
      deliveries with a rotation of >/=90 degrees performed between July 1992 and
      September 1995 were identified (n = 113). For controls 167 forceps deliveries
      with rotations of </=45 degrees were randomly selected. Control deliveries
      occurred during the same time period and were matched to within 2 weeks of
      gestational age as well as to nulliparous versus parous status. The majority of
      deliveries were low; however, some midforceps deliveries were also included.
      RESULTS: Forceps rotations of >/=90 degrees accounted for 0.8% of all deliveries.
      A major fetal injury, defined as a skull fracture, subdural hematoma, brachial
      plexus or a sixth or seventh cranial nerve injury, occurred in 10.2% of
      deliveries with rotations of </=45 degrees and in 9.7% with rotations of >/=90
      degrees. The only permanent injury was a brachial plexus palsy that occurred with
      a forceps rotation of 45 degrees. Rotations of >/=90 degrees were not associated
      with umbilical arterial acidemia below 7.0 or 7.1 compared with rotations of
      </=45 degrees. Rotations of >/=90 degrees were associated with longer maternal
      hospital stays (P =.009). Neither lacerations of the birth canal, third- or
      fourth-degree episiotomies, or fall in the maternal hematocrit correlated with
      the degree of forceps rotation. CONCLUSIONS: Advanced degrees of forceps
      rotations do not result in any clinically significant increase in infant or
      maternal morbidity relative to that encountered with lesser degrees of forceps
      rotation.

PMID- 9914610
TI  - Maternal body fat and water during pregnancy: do they raise infant birth weight?
AB  - OBJECTIVE: Our purpose was to determine the relation to infant birth weight of
      maternal fat and lean tissue during early and late pregnancy. DESIGN: Total and
      net maternal pregnancy weight, fat, and water were determined from measurements
      of total body water, body density, and bone mineral mass in 200 women, with the
      use of a multicompartment model for body fat estimation in early and late
      pregnancy. Regression modeling was used to determine the relation of maternal
      body composition to birth weight, with control for maternal age, height, parity,
      and race and for infant gestational age and sex. RESULTS: Maternal weight and
      body water at term were significantly associated with infant birth weight, but
      maternal body fat at term was not. These relations remained when maternal net
      values were used for weight, fat, and water to eliminate the contribution of the
      conceptus to these components. CONCLUSION: In well-nourished women delivering at
      term, maternal body fat near term does not contribute significantly to infant
      birth weight, but maternal body water does.

PMID- 9914611
TI  - Estimates of the risk of cardiovascular death attributable to low-dose oral
      contraceptives in the United States.
AB  - OBJECTIVE: Our purpose was to estimate the annual risk of death in the United
      States from cardiovascular disease attributable to low-dose combination oral
      contraceptives. STUDY DESIGN: Estimates of the risk of death from cardiovascular
      disease attributable to low-dose oral contraceptives were modeled on data from
      studies published through 1997 and from age-specific mortality rates in the
      United States for 1993 and 1994. RESULTS: Attributable risk of death from
      cardiovascular disease resulting from oral contraceptive use is 0.06 and 3.0 per
      100,000 nonsmokers 15 to 34 years of age and 35 to 44 years of age, respectively.
      In smokers this risk increases, respectively, to 1.73 and 19.4 per 100,000 users
      in these 2 age groups; however, 97% and 85% of this risk is due to the combined
      effects of smoking and using oral contraceptives. The attributable risk of death
      from cardiovascular disease in nonsmoking oral contraceptive users is lower than
      the risk of death from pregnancy in nonusers of oral contraceptives at all ages;
      however, among smoking oral contraceptive users more than 35 years of age, the
      excess risk of death from oral contraceptives is higher than the risk of death
      from pregnancy. CONCLUSION: There is virtually no excess attributable risk of
      death from cardiovascular disease related to oral contraceptive use in young
      women. However, smokers more than 35 years of age should use a nonestrogen
      contraceptive.

PMID- 9914613
TI  - Tight nuchal cord morbidity and mortality.

PMID- 9914614
TI  - Ultrasonographic evaluation of endometrial disease in postmenopausal patients
      with breast cancer and tamoxifen treatment.

PMID- 9914615
TI  - Induction of labor with misoprostol for premature rupture of membranes beyond
      thirty-six weeks' gestation.

PMID- 9914616
TI  - In defense of Apgar scores.

PMID- 9914619
TI  - A role for estriol in human labor, term and preterm.
AB  - Although estriol has been studied as an indicator of fetal well-being in the
      past, its broader biologic role has not been elucidated. Estriol in the maternal
      compartment closely reflects fetal adrenal activity, and increased fetal adrenal
      activity prior to the onset of labor is a common link in mammalian parturition.
      In humans, estriol increases before spontaneous labor and may be a clinically
      useful marker for some cases of preterm labor.

PMID- 9914620
TI  - Accuracy of salivary estriol testing compared to traditional risk factor
      assessment in predicting preterm birth.
AB  - OBJECTIVE: The objective was to compare the predictive accuracy (percentage of
      correct vs incorrect predictions) of salivary estriol levels (SalEst; Biex, Inc,
      Dublin, Calif) with that of the modified Creasy score for predicting preterm
      labor followed by preterm delivery. STUDY DESIGN: A triple-blinded prospective
      trial was conducted at 8 US centers. RESULTS: Among 601 evaluable patients,
      serial salivary estriol testing correctly predicted the appropriate outcome 91%
      of the time and the Creasy scoring method correctly predicted the appropriate
      outcome 75% of the time (McNemar test P <. 001). Among subjects with Creasy
      scores >/=10 (high-risk group, n = 152), use of salivary estriol testing
      correctly predicted the end point 87% of the time, compared with only 7.2%
      correctly predicted by modified Creasy scoring (McNemar test P <.001).
      CONCLUSION: Salivary estriol assessment was more accurate in predicting outcome
      than was modified Creasy scoring.

PMID- 9914621
TI  - Serial betamethasone administration: effect on maternal salivary estriol levels.
AB  - OBJECTIVE: Maternal salivary estriol levels are an indirect measure of fetal
      adrenal activity, which may be affected by administration of betamethasone. The
      objective was to compare sequential salivary estriol levels in patients receiving
      serial betamethasone therapy with those of healthy pregnant patients. STUDY
      DESIGN: Ten patients at high risk for preterm delivery were asked to obtain
      salivary specimens before and 1 to 2 days after each administration of weekly
      betamethasone treatments between 24 and 32 weeks' gestation. These values were
      compared with those of specimens obtained throughout gestation in healthy women
      who were not delivered preterm. Unconjugated salivary estriol was measured with a
      sensitive and specific enzyme-linked immunoassay (Biex, Inc, Dublin, Calif).
      RESULTS: The effect of betamethasone on salivary estriol levels did not change
      with time, showing an average of 23.1% drop from pretreatment to posttreatment
      levels but rebounding to the same starting level before the next dose. When
      weekly pretreatment values were looked at across time, the geometric mean of the
      individual patients' slopes did not differ significantly from no change. The same
      was true of the posttreatment values. The rate of change with advancing gestation
      was compared between 182 control subjects and the 10 study subjects. The average
      change was +8.8% per week in the control subjects and -1.3% per week in the study
      patients (P =.003). CONCLUSIONS: Maternal administration of betamethasone
      significantly suppressed salivary estriol levels. These levels returned to
      pretreatment values each week before the next dose; however, the rise normally
      associated with advancing gestational age was not observed.

PMID- 9914622
TI  - Diurnal variation in saliva estriol level during pregnancy: a pilot study.
AB  - OBJECTIVE: The object of the study was to characterize daily values and patterns
      of salivary estriol levels during normal pregnancy at mid to late gestation.
      STUDY DESIGN: We measured salivary estriol levels in a clinical research center
      setting with an established enzyme-linked immunosorbent assay. Fourteen pregnant
      women (24-36 weeks' gestation) submitted unstimulated saliva samples hourly from
      10:00 am until 10:00 pm and at midnight and 2:00, 4:00, 6:00, and 8:00 am.
      RESULTS: Each subject demonstrated greater salivary estriol levels at night
      (10:00 pm-6:00 am) than in the daytime (8:00 am-9:00 pm, P <.001). Salivary
      estriol levels consistently increased at 10:00 pm, peaked at 4:00 am, and
      returned to daytime levels between 6:00 and 7:00 am. Salivary estriol
      concentrations were stable during daylight hours. CONCLUSIONS: (1) There was a
      dramatic diurnal variation in salivary estriol levels (nadir during daylight with
      nighttime apogee). (2) Diurnal patterns and salivary estriol levels were
      consistent in each of 14 subjects evaluated in the latter half of pregnancy.
      Samples for baseline measurements of salivary estriol level should be obtained
      during daylight hours (8:00 am-8:00 pm).

PMID- 9914623
TI  - Saliva as a fluid for measurement of estriol levels.
AB  - OBJECTIVE: The purpose was to establish saliva as a reliable sample for the
      determination of estriol levels in pregnant women. STUDY DESIGN: Literature and
      laboratory analyses were used to develop an assembly system to collect and
      analyze saliva for estriol level. RESULTS: An enzyme-linked immunoassay for
      estriol has been developed to use whole saliva samples. Analytic performance
      characteristics for the assay have been determined to be appropriate for clinical
      determination of preterm risk assessment. CONCLUSION: Saliva can serve as a
      reliable sample for estriol determination when coupled with an appropriate assay
      method.

PMID- 9914624
TI  - A central theory of preterm and term labor: putative role for corticotropin
      releasing hormone.
AB  - Near the end of human pregnancy the concentration of placental corticotropin
      releasing hormone in maternal blood rises exponentially. The rate of elevation of
      corticotropin-releasing hormone and its duration through time have been linked to
      the time of onset of labor. Paradoxically, although glucocorticoids are known to
      inhibit corticotropin-releasing hormone production within the hypothalamic
      pituitary-adrenal axis, cortisol actually increases corticotropin-releasing
      hormone levels in several areas outside the hypothalamus, including the placenta.
      Placental corticotropin-releasing hormone may be an important component of a
      system that controls the normal maturation of the fetus and signals the
      initiation of labor. Abnormal elevations in corticotropin-releasing hormone,
      which may be a hormonal response to stressors arising in either the mother,
      placenta, or fetus, may prove to participate in the premature onset of
      parturition.

PMID- 9914625
TI  - Placental corticotropin-releasing hormone: function and regulation.
AB  - Corticotropin-releasing hormone is a neuropeptide placentally expressed among
      mammals only in primates. Its expression increases as much as 100 times during
      the last 6 to 8 weeks of pregnancy and is paradoxically stimulated by
      glucocorticoids. Increasing evidence suggests that placental corticotropin
      releasing hormone may have evolved in primates to stimulate fetal
      adrenocorticotropin release and adrenal steroidogenesis, thus satisfying the high
      demand for synthesis of dehydroepiandrosterone, the predominant source of
      placental estradiol. Concomitant stimulation by placental corticotropin-releasing
      hormone of fetal cortisol and dehydroepiandrosterone would couple the
      glucocorticoid effects on fetal organ maturation with the timing of parturition,
      an obvious benefit in postnatal survival.

PMID- 9914626
TI  - New approaches to the diagnosis of preterm labor.
AB  - There is a pressing need to develop accurate methods of diagnosing true preterm
      labor because of the availability of potent tocolytic drugs and the known
      beneficial effects of antenatal glucocorticoid administration on neonatal
      outcomes of premature infants. Maternal plasma corticotropin-releasing hormone
      concentrations are elevated in women with threatened preterm labor between 28 and
      36 weeks' gestation who give birth within 24 hours. In addition, the ratio of
      cortisol to corticosteroid binding capacity is elevated in the plasma of women
      who give birth within 24 hours. These data support the design and conduct of a
      prospective clinical trial to determine the positive and negative predictive
      values of these markers for preterm birth in women with symptoms.

PMID- 9914627
TI  - Reproductive placental corticotropin-releasing hormone and its clinical
      implications.

PMID- 9914628
TI  - Immunoendocrinology of preterm labor: the link between corticotropin-releasing
      hormone and inflammation.
AB  - Preterm labor is the final common pathway after several potential insults to the
      uterus or fetus. The preterm labor syndrome may be precipitated by several
      different pathophysiologic events, including intrauterine infection, uterine
      ischemia, uterine overdistention, hormonal disturbances, and other problems.
      Intrauterine infections (both clinically evident and subclinical) are associated
      with increased amniotic fluid concentrations of proinflammatory cytokines, and
      gestational tissues and the fetus are potential sources of these cytokines. In
      addition to culture-proven intrauterine infection, there may be an "intrauterine
      inflammatory response syndrome" that could account for cases of preterm labor in
      which no infectious organism can be identified. Because the immunologic and
      endocrinologic systems regulate each other extensively, there is potential for
      corticotropin-releasing hormone to regulate inflammatory responses and vice
      versa. The cytokine interleukin 1 stimulates production of corticotropin
      releasing hormone, and corticotropin-releasing hormone in turn regulates cytokine
      production by immune effector cells. Because maternal stress is associated with
      preterm birth, abnormalities in the regulation of corticotropin-releasing hormone
      and the production of inflammatory cytokines may be a mechanism that could form
      the pathophysiologic basis for this association.

PMID- 9914629
TI  - Maternal plasma corticotropin-releasing hormone associated with stress at 20
      weeks' gestation in pregnancies ending in preterm delivery.
AB  - OBJECTIVE: This study tested the hypothesis that maternal stress is associated
      with elevated maternal levels of corticotropin releasing hormone and activation
      of the placental-adrenal axis before preterm birth. STUDY DESIGN: In a behavior
      in pregnancy study, 524 ethnically and socioeconomically diverse women were
      followed up prospectively and evaluated at 3 gestational ages: 18 to 20 weeks, 28
      to 30 weeks, and 35 to 36 weeks. Maternal variables included demographic data,
      medical conditions, perceived stress level, and state anxiety. Maternal plasma
      samples were collected at each gestational age. Eighteen case patients with
      spontaneous onset of preterm labor were matched against 18 control subjects who
      were delivered at term, and their samples were assayed for corticotropin
      releasing hormone, adrenocorticotropic hormone, and cortisol by means of
      radioimmunoassay. Statistical tests were used to examine mean differences in
      these hormones. In addition, the relationship between stress level and each
      hormone was tested with a Pearson correlation coefficient and hierarchic multiple
      regressions in each group. RESULTS: Patients who had preterm delivery had
      significantly higher plasma corticotropin-releasing hormone levels than did
      control subjects at all 3 gestational ages (P <.0001). Analyses did not find any
      differences in reported levels of stress between 18 to 20 weeks' gestation and 28
      to 30 weeks' gestation. A hierarchic multiple regression indicated that maternal
      stress level at 18 to 20 weeks' gestation and maternal age accounted for a
      significant amount of variance in corticotropin-releasing hormone at 28 to 30
      weeks' gestation, after controlling for corticotropin-releasing hormone at 18 to
      20 weeks' gestation (P <. 001). In addition, patients who were delivered preterm
      had significantly elevated plasma levels of adrenocorticotropic hormone at all 3
      gestational ages (P <.001) and significantly elevated cortisol levels at 18 to 20
      weeks' gestation and 28 to 30 weeks' gestation (P <.001). CONCLUSION: Maternal
      plasma levels of corticotropin-releasing hormone are significantly elevated at as
      early as 18 to 20 weeks' gestation in women who are subsequently delivered
      preterm. Changes in corticotropin-releasing hormone between 18 to 20 weeks'
      gestation and 28 to 30 weeks' gestation are associated with maternal age and
      stress level at 18 to 20 weeks' gestation. Maternal stress and corticotropin
      releasing hormone levels may be potential markers for the patient at risk for
      preterm birth. Activation of the placental maternal pituitary-adrenal axis is
      consistent with the classic endocrine response to stress.

PMID- 9914630
TI  - Stress-associated preterm delivery: the role of corticotropin-releasing hormone.
AB  - OBJECTIVE: The study's objective was to provide an introduction to the role of
      corticotropin-releasing hormone in preterm delivery associated with stress. STUDY
      DESIGN: A selective review of the current literature relevant to the objective
      was undertaken. Published data were analyzed for relevance to the biochemical
      model presented. RESULTS: Preterm delivery is a leading cause of neonatal
      morbidity and mortality. Efforts to prevent preterm delivery have been greatly
      hampered by a poor understanding of the underlying pathophysiology. There is
      increasing clinical and laboratory evidence that many preterm deliveries result
      from maternal and fetal stress, which activates cells in the placenta, decidua,
      and fetal membranes to produce corticotropin-releasing hormone. Corticotropin
      releasing hormone in turn enhances prostaglandin production in these tissues to
      promote parturition. CONCLUSION: Corticotropin-releasing hormone plays an
      important role in the etiology of preterm delivery associated with maternal or
      fetal stress.

PMID- 9914631
TI  - How far upstream or downstream is corticotropin-releasing hormone in the overall
      process of parturition in rhesus monkeys?

PMID- 9914632
TI  - Corticotropin-releasing hormone and the fetoplacental clock: an Australian
      perspective.

PMID- 9914633
TI  - Stress and reproductive failure: an evolutionary approach with applications to
      premature labor.
AB  - This article takes an evolutionary approach to the study of reproductive failure,
      drawing attention to the importance of reproductive failure among mammals as a
      means of timing reproduction in response to a variable environment. These
      concepts also apply to the diagnosis and treatment of prematurity, because before
      the advent of modern medicine most premature births probably constituted failed
      reproduction. Problems in the diagnosis and treatment of reproductive failure are
      described, with specific parallels drawn between the diagnoses and treatments of
      infertility and prematurity.

PMID- 9914634
TI  - Childhood derivatives of high and low reactivity in infancy.
AB  - A group of 193 children, classified as high or low reactive to stimulation at 4
      months and observed again at 14 and 21 months, were observed at 4 1/2 years of
      age for behavioral signs of inhibited or uninhibited behavior. Children who had
      been high reactive were less spontaneous and less sociable than those who had
      been classified as low reactive, but only a small proportion of children
      maintained a consistently inhibited or uninhibited phenotype at all ages.

PMID- 9914635
TI  - Is affect aversive to young children with autism? Behavioral and cardiac
      responses to experimenter distress.
AB  - The aim of this study was to determine whether displays of negative emotions are
      more aversive to young children with autism than displays of neutral emotions.
      The attention, behavioral reactions, facial affect, and cardiac responses of 22
      autistic and 22 mentally retarded 3-5-year-old children were compared when an
      experimenter pretended to hurt herself and showed strong distress in contrast to
      when the experimenter pretended to hurt herself but showed only neutral affect.
      The children in both diagnostic groups looked more at the experimenter and
      appeared more interested and concerned when she displayed strong distress than
      when she showed neutral affect. The heart rate of the mentally retarded children
      decreased during the distress condition relative to a baseline condition, but the
      heart rate of the children with autism did not change across conditions. In
      summary, the children with autism gave no evidence of being overly aroused by or
      avoiding the distressed experimenter.

PMID- 9914636
TI  - Assessing salivary cortisol in studies of child development.
AB  - In a series of studies, we evaluated the susceptibility of radioimmunoassays
      (RIA) for saliva cortisol to interference effects caused by oral stimulants used
      to facilitate saliva collection in studies with children. When added directly to
      saliva samples, oral stimulants (drink mix crystals) artificially inflated
      estimated cortisol concentrations. The magnitude of the interference effect was
      concentration-dependent and more pronounced for some stimulants and RIA
      procedures than for others. Analysis of samples collected using oral stimulants
      from child and adult participants confirmed stimulant interference as an
      extraneous source of variability in measured saliva cortisol. Associations
      between serum and saliva cortisol and between saliva cortisol and "behavioral"
      variables were attenuated by stimulant interference. A survey of six large child
      studies estimated interference effects, indexed by low sample pH, to be present
      in 14.7% of the 1,148 total saliva samples, or 2%-54% (M = 22%) of samples within
      each study. Recommendations to minimize the impact of stimulant interference in
      studies involving salivary cortisol in the context of child health and
      development are outlined.

PMID- 9914637
TI  - Chronic residential crowding and children's well-being: an ecological
      perspective.
AB  - Chronic residential crowding is associated with difficulties in behavioral
      adjustment at school, poor academic achievement, heightened vulnerability to the
      induction of learned helplessness, elevated blood pressure, and impaired parent
      child interpersonal relationships among a sample of working-class, 10-to 12-year
      old children living in urban India. The significant main effects of residential
      crowding on blood pressure and learned helplessness are moderated by gender.
      Residential crowding is positively associated with blood pressure only among boys
      and with helplessness only among girls. All analyses statistically control for
      household income. We then demonstrate that perceived parent-child conflict
      functions as an underlying, intervening process that largely accounts for several
      correlates of household crowding among children.

PMID- 9914638
TI  - The foundations of literacy: learning the sounds of letters.
AB  - Learning the sounds of letters is an important part of learning to read and
      spell. To explore the factors that make some letter-sound correspondences easier
      for children to learn than others, we first analyzed knowledge of letters' sounds
      (and names) by 660 children between 3 1/2 and 7 1/2 years old. A second study
      examined pre-schoolers' (M age 4 years, 11 months) ability to learn various sound
      letter mappings. Together, the results show that an important determinant of
      letter-sound knowledge is whether the sound occurs in the name of the letter and,
      if so, whether it is at the beginning or the end. The properties of the sound
      itself (consonant versus vowel, sonorant versus obstruent, stop versus
      continuant) appear to have little or no influence on children's learning of basic
      letter-sound correspondences. The findings show that children use their knowledge
      of letters' names when learning the letters' sounds rather than memorizing letter
      sound correspondences as arbitrary pairings.

PMID- 9914639
TI  - Tolerance and intolerance: children's and adolescents' judgments of dissenting
      beliefs, speech, persons, and conduct.
AB  - Tolerant and intolerant judgments of different types of dissent were examined.
      One hundred sixty participants (aged 7.3, 10.4, 13.6, and 20.1) made judgments
      about dissenting beliefs, speech, practices, and people engaged in those
      practices. Across all ages, participants were more tolerant (1) of the holding of
      dissenting beliefs than of their expression, (2) of the expression of beliefs
      than of the persons engaged in acts based on those beliefs, and (3) of the
      persons than of the acts. Tolerance of dissenting beliefs and speech increased
      with age. Although, at all ages, participants were intolerant of the practices,
      they were relatively more tolerant of practices grounded in cultural contexts.
      Participants were more tolerant of people espousing dissenting information than
      dissenting values. We concluded that tolerance and intolerance coexist at all
      ages and hinge on what individuals are asked to tolerate and on the sense in
      which they are asked to tolerate it.

PMID- 9914640
TI  - Assessing young children's views of their academic, social, and emotional lives:
      an evaluation of the self-perception scales of the Berkeley Puppet Interview.
AB  - In a prospective, longitudinal study we examined the psychometric properties of
      the self-perception scales of the Berkeley Puppet Interview (BPI). A total sample
      of 97 young children were assessed with the BPI at 3 time points: preschool,
      kindergarten, and first grade. The BPI assesses young children's self-perceptions
      of their school adjustment in 6 domains: academic competence, achievement
      motivation, social competence, peer acceptance, depression-anxiety, and
      aggression-hostility. Results showed that 4 1/2- to 7 1/2-year-olds possess a
      multidimensional self-concept that can be reliably measured and that the BPI is
      sensitive to normative changes and individual differences in young boys' and
      girls' views of themselves. Support for the method's validity was derived from
      consistent and meaningful patterns of convergence between children's self
      perceptions and ratings by adult informants--mothers, fathers, and teachers--as
      well as standardized test scores. In fact, in this study, the concordance between
      young children's self-reports and parallel ratings by teachers or mothers were
      consistently as strong as if not stronger than the concordance between mothers'
      and teachers' ratings.

PMID- 9914641
TI  - Does welfare affect family processes and adolescent adjustment?
AB  - Recent welfare reform legislation requires increased parental work effort and
      imposes time limits on the receipt of federal assistance. These changes were
      based in part on assumptions that parental welfare receipt may be negatively
      related to family processes and children's attitudes and behaviors. Currently,
      researchers know little about the effects of welfare by itself relative to the
      effects of related variables such as family demographic characteristics, economic
      strain, and neighborhood factors on processes among families with adolescent
      children. This study investigates parenting behaviors, parent-adolescent
      relationships, and adolescent attitudes and behaviors in three family types.
      Families of adolescents ages 11-15 who received income from Aid to Families with
      Dependent Children (AFDC) in the previous 12 months are compared with poor
      families who have not received AFDC in the last year and with families who are
      neither poor nor welfare dependent. We found minimal support for the hypothesis
      that welfare is negatively related to family processes and adolescent attitudes
      and behaviors, although mothers receiving welfare report fewer effective parent
      management practices than their poor non-welfare counterparts. Implications of
      the findings for current social policy debates are discussed.

PMID- 9914642
TI  - Intrapersonal and maternal correlates of aggression, conflict, and externalizing
      problems in toddlers.
AB  - Research has shown that 2-year-olds engage in peer-directed aggression and
      initiation of conflict. However, there has been little consideration of the
      factors associated with variability in toddlers' aggression. One hundred and four
      toddlers (52 females) were observed for 35 min of free play with a same-sex peer,
      with both mothers present. Experience in early out-of-home care was not related
      to aggression. Toddlers' observed and mother-rated dysregulated temperament, and
      mothers' use of warmth and negative dominance during interactions with their
      children, were used to predict toddlers' aggression and maternal ratings of
      externalizing difficulties. Boys were observed to be more aggressive than girls.
      Regression analyses showed that, after controlling for main effects, the
      interaction of child gender, temperament, and maternal negative dominance
      predicted both outcomes. Observed aggression and mother-reported externalizing
      problems were associated significantly with dysregulated temperament only for
      boys with mothers who demonstrated relatively high levels of negative dominance.

PMID- 9914643
TI  - Response decision processes in relational and overt aggression.
AB  - Response decision processes of relationally and overtly aggressive children were
      assessed for both boys and girls. A hypothetical-situation instrument, adapted
      from past research, was used to assess children's evaluations of relationally
      aggressive and overtly aggressive responses to both relational and instrumental
      conflict situations for third-through sixth-grade children (n = 1,166). Findings
      revealed that both overtly aggressive boys and overtly aggressive girls evaluated
      overtly aggressive responses to instrumental conflict situations in relatively
      positive ways. Further, overtly aggressive girls, but not boys, evaluated overtly
      aggressive responses to relational conflict situations in relatively positive
      ways. Additionally, relationally aggressive boys evaluated relationally
      aggressive responses to instrumental conflict situations in relatively positive
      ways. Gender differences were also obtained. Boys evaluated overt aggression more
      positively, whereas girls evaluated relational aggression more positively.
      Implications of these findings for the role of gender, situation type, response
      type, and aggression type for our understanding of children's social information
      processing are discussed.

PMID- 9914644
TI  - Family relationships and children's emotional adjustment as correlates of
      maternal and paternal differential treatment: a replication with toddler and
      preschool siblings.
AB  - Recent behavioral genetic research emphasizes the nonshared family environment as
      an important contributor to psychological differences between siblings raised in
      the same family. Most studies of nonshared sibling experiences have examined the
      effects of differential maternal and paternal treatment separately and have not
      examined family-level processes. This study attempted to replicate the findings
      of McHale, Crouter, McGuire, and Updegraff and also of Volling in which relations
      between family patterns of differential parental treatment, child outcomes, and
      family functioning were examined. Questionnaire data were collected from 60
      maritally intact families with toddler and preschool siblings. Congruence in
      mothers' and fathers' reports of differential treatment (i.e., similar treatment
      from both mother and father) was most frequent. Parents' reports of differential
      enjoyment were related to differential favoritism, whereas their reports of
      differential discipline were not. Both mothers and fathers were more likely to
      discipline the older sibling than the younger toddler. Sibling and marital
      harmony characterized families in which the father disciplined the older sibling
      more and mothers disciplined the two children equally. Incongruent patterns of
      differential favoritism (i.e., one parent treats the children equally while the
      other favors one child) were associated with marital distress. Preschool siblings
      exhibited greater internalizing and externalizing symptoms when both mothers and
      fathers disciplined them more than their younger sibling. The findings of this
      study with very young siblings differ in some respects from those with older
      children and suggest that future research needs to examine differential parental
      treatment as a developmental process across childhood.

PMID- 9914645
TI  - Parenting and preschooler attachment among low-income urban African American
      families.
AB  - This study examined the parental correlates of child attachment in a preschool
      aged, economically disadvantaged, urban, African American sample. Sixty-nine 4-
      to 5-year-olds and their primary caregivers participated in the Strange Situation
      assessment procedure. Based on Cassidy and Marvin's classification system for
      preschoolers, 61% of the children were classified as securely attached, with
      girls being significantly more likely to be securely attached than boys (74%
      versus 45%). The majority of the insecure attachments were of the avoidant
      variety. Consistent with attachment theory, parents of securely attached children
      were rated as significantly more warm and accepting and less controlling with
      their children than were parents of insecurely attached preschoolers. Relative to
      parents of securely attached preschoolers, parents of children judged to be
      insecurely attached reported being more likely to use corporal punishment and
      less likely to use verbal reminders when their children misbehaved. Parenting was
      associated with attachment over and above the effects of child sex.

PMID- 9914646
TI  - Parent influences on adolescent peer orientation and substance use: the interface
      of parenting practices and values.
AB  - This study examines how experiences in the family domain may magnify or mitigate
      experiences in the peer domain, and how processes in both milieus may influence
      adolescent substance use. The data derived from 666 European American mother
      adolescent dyads and 510 European American father-adolescent dyads. Consistent
      with individuation-connectedness theory, mothers' responsiveness lessened their
      adolescents' orientation to peers, which, in turn, reduced adolescent substance
      use. This process was moderated by maternal values regarding adolescent alcohol
      use; that is, the relation of maternal responsiveness to adolescent substance use
      depended on the extent of maternal approval or disapproval of adolescent alcohol
      use. Among fathers, closer monitoring was directly associated with less
      adolescent substance use, with stronger effects among fathers who held more
      disapproving values regarding adolescent alcohol use. Theoretical,
      methodological, and pragmatic implications are given.

PMID- 9914647
TI  - Enantioselectivity of bunitrolol 4-hydroxylation is reversed by the change of an
      amino acid residue from valine to methionine at position 374 of cytochrome P450
      2D6.
AB  - The enantioselectivity of 4-hydroxylation of bunitrolol (BTL), a beta
      adrenoceptor blocking drug, was studied in microsomes from human liver, human
      hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing
      CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)-BTL
      was 2.1-fold that of (-)-BTL, and that the Km value for (+)-BTL was lower than
      that for the (-)-antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)
      BTL being 2.1-fold over its (-)-antipode. CYP2D6 (CYP2D6-met) expressed in Hep G2
      cells had a methionine residue at position 373 of the amino acid sequence and a
      rat-type N-terminal peptide (MELLNGTGLWSM) instead of the human-type
      (MGLEALVPLAVIV), and showed enantioselectivity of [(+)-BTL < (-)-BTL] for the
      rate of BTL 4-hydroxylation. In contrast, enantioselectivity [(+)-BTL > (-)-BTL]
      for Hep G2-CYP2D6 (CYP2D6-val) with a human-type N-terminal peptide that had a
      valine residue at 374, which corresponds to the methionine of the CYP2D6-met
      variant, was the same as that for human liver microsomes. We further confirmed
      that CYP2D6-met and CYP2D6-val expressed in human lymphoblastoid cells, both of
      which have methionine and valine, respectively, at position 374 and a human-type
      N-terminal peptide, exhibited the same enantioselectivities as those obtained
      from CYP2D6-met and CYP2D6-val expressed in the Hep G2 cell system. These results
      indicate that the amino acid at 374 of CYP2D6 is one of the key factors
      influencing the enantioselectivity of BTL 4-hydroxylation.

PMID- 9914648
TI  - Characterization of esterases involved in the stereoselective hydrolysis of ester
      type prodrugs of propranolol in rat liver and plasma.
AB  - An inhibition study showed that the stereoselective hydrolysis of butyryl
      propranolol (butyryl PL) in rat liver microsomes and plasma involves
      carboxylesterase. The hydrolysis of (S)-butyryl PL in plasma was specifically
      inhibited by eserine and bis-nitrophenyl phosphate (BNPP), compared to the (R)
      isomer, despite the non-stereoselective hydrolysis of butyryl PL in plasma. In
      addition, inhibition of hydroloysis by eserine and BNPP showed little
      stereoselectivity for butyryl PL in liver, although liver microsomes showed an
      (S)-preferential hydrolysis for butyryl PL (R/S ratio of Vmax/Km: 2.1 +/- 0.2).
      The hydrolysis of butyryl PL was not inhibited by a polyclonal antibody against a
      high affinity carboxylesterase (hydrolase A, RH1). Moreover, the high Km value
      and the high IC50 for phenylmethylsulfonyl fluoride (PMSF) against the hydrolysis
      of butyryl PL in rat liver microsomes suggest that a low affinity
      carboxylesterase (perhaps hydrolase B) might be involved in this hydrolysis in
      rat liver.

PMID- 9914649
TI  - Preparation and configuration of racemic and optically active analgesic
      cycloaminoalkylnaphthalenes.
AB  - Cycloaminoalkylnaphthalene 3 shows interesting opioid-like analgesic properties.
      It possesses two chiral centers and can exist as two racemic pairs and four
      diastereomers. Since the binding of opioids with receptors is stereoselective, it
      was important to have the two racemic pairs as well as the four diastereomers. In
      this paper the synthesis of the (2R,3S/2S,3R) racemate and the (2R,3S) and
      (2S,3R) enantiomers of the 1,2-dimethyl-3-[2-(6-hydroxynaphthyl)]-3
      hydroxypyrrolidine 3 is considered and the determination of absolute
      configuration is described. The (2R,3S/2S,3R)-3 racemate and the (2R,3S)-3 and
      (2S,3R)-3 enantiomers were prepared by reaction of the racemic and optically
      active 1,2-dimethyl-3-pyrrolidone 2, respectively, with the lithiation product
      obtained from 2-bromo-6-tetrahydropyranyloxy-naphthalene 1 and acidic hydrolysis.
      The above-mentioned enantiomers of 3 were also obtained by optical resolution via
      fractional crystallization of the salts with D- and L-tartaric acids. The
      configuration of the optically active compounds was determined by X-ray analysis
      of a crystal of (-)-(2S,3R)-3.HCl.H2O. The pharmacological test HPT showed that (
      )-(2S,3R)-3.HCl.H2O enantiomer is able to induce opioid-like analgesia with a
      relative potency 1.5 times that of (2R,3S/2S,3R)-3 and approximately 1.5 times
      that of morphine.

PMID- 9914650
TI  - Enantioselectivity in the metabolism of mexiletine by conjugation in female
      patients with the arrhythmic form of chronic Chagas' heart disease.
AB  - The phenomenon of enantioselectivity in the metabolism of mexiletine (MEX)
      conjugation was investigated in eight female patients with the arrhythmic form of
      chronic Chagas' heart disease treated with racemic mexiletine hydrochloride (two
      100 mg capsules every 8 hr). Blood samples were collected up to 24 hr after the
      administration of the morning dose, with discontinuation of the subsequent doses
      during the study period. Plasma concentrations of N-hydroxymexiletine glucuronide
      were calculated as the difference between the concentrations of unchanged and
      total (unchanged + conjugated) MEX enantiomers. Total plasma MEX concentrations
      were analyzed by HPLC after enzymatic hydrolysis with beta-glucuronidase, the
      formation of diastereomeric derivatives with the chiral reagent N-acetyl-L
      cysteine/o-phthalaldehyde, and fluorescence detection. The differences in the
      pharmacokinetic parameters of the enantiomers were evaluated by the paired t
      test. The plasma concentrations of the (+)-(S)-MEX did not differ before and
      after enzymatic hydrolysis. The pharmacokinetic parameters calculated for (-)-(R)
      N-hydroxymexiletine glucuronide are presented as means (95% confidence interval):
      maximum plasma concentration Cmax = 194.0 ng.ml-1 (154.3-233.7), time to maximum
      plasma concentration tmax = 1.4 hr (0.3-2.5), area under the plasma concentration
      versus time curve AUC0-24 = 2099.2 ng.h.ml-1 (1585.6-2612.6), elimination half
      life t1/2 beta = 12.8 hr (9.9-15.6) and extent of conjugation of 31.6% (24.3
      38.9%). The present data indicate stereospecific conjugation of (-)-(R)-N
      hydroxymexiletine in the female patients with the arrhythmic form of Chagas'
      heart disease.

PMID- 9914651
TI  - Reversible binding of ethacrynic acid to human serum albumin: difference circular
      dichroism study.
AB  - The reversible binding of ethacrynic acid was characterized by a difference
      circular dichroism method. A 2/1 stoichiometry was determined for the
      [drug]/[HSA] (human serum albumin) complex. The reversible binding of ethacrynic
      acid to HSA determines direct competition with ligands that selectivity bind to
      site II and to the fatty acid site. Furthermore, indirect competition was shown
      for ligands for site I (anti-cooperative) and to site III (cooperative).

PMID- 9914652
TI  - Immobilized horse liver alcohol dehydrogenase as an on-line high-performance
      liquid chromatographic enzyme reactor for stereoselective synthesis.
AB  - Horse liver alcohol dehydrogenase (HLADH) has been non-covalently immobilized on
      an immobilized artificial membrane (IAM) high-performance liquid chromatography
      (HPLC) stationary phase. The resulting IAM-HLADH retained the reductive activity
      of native HLADH as well as the enzyme's enantioselectivity and
      enantiospecificity. HLADH was also immobilized in an IAM HPLC stationary phase
      prepacked in a 13 x 4.1 mm ID column to create an immobilized enzyme reactor
      (HLADH-IMER). The reactor was connected through a switching valve to a column
      containing a chiral stationary phase (CSP) based upon p-methylphenylcarbamate
      derivatized cellulose (Chiralcel OJR-CSP). The results from the combined HLADH
      IMER/CSP and chromatographic system demonstrate that the enzyme retained its
      activity and stereoselectivity after immobilization in the column and that the
      substrate and products from the enzymatic reduction could be transferred to a
      second column for analytical or preparative separation. The combined HLADH
      IMER/CSP system is a prototype for the preparative on-line use of cofactor
      dependent enzymes in large-scale chiral syntheses.

PMID- 9914653
TI  - Stereoselective urinary excretion of bupivacaine and its metabolites during
      epidural infusion.
AB  - A sensitive and efficient chiral assay for bupivacaine and its three principal
      metabolites desbutylbupivacaine, 4'-hydroxybupivacaine, and 3'-hydroxybupivacaine
      has been applied to urine from five male patients receiving postoperative
      epidural infusions of rac-bupivacaine fentanyl over 60-120 hr. The fraction of
      the dose of bupivacaine (total dose 840-2093 mg) accounted for in urine was 75 +/
      6%. The rate of excretion of bupivacaine enantiomers' approximated a steady
      state after approximately 30 hr with values of 1.27 +/- 0.26 and 0.76 +/- 0.13 mg
      hr-1 for (R)- and (S)-enantiomers, respectively. The fraction of the dose of
      bupivacaine enantiomer excreted unchanged in the urine (fe) varied from 14.3% to
      39.1% for (+)-(R)-bupivacaine and 9.2% to 14.0% for (-)-(S)-bupivacaine in the
      five patients. The rate of excretion of all metabolites also reached a steady
      state after approximately 30 hr and the relative amounts of metabolites excreted
      into urine (fm) suggest bupivacaine is subject to regioselective and
      stereoselective clearance, which may vary from patient to patient.

PMID- 9914654
TI  - Evaluation of the macrocyclic antibiotic LY333328 as a chiral selector when used
      as a mobile phase additive in narrow bore HPLC.
AB  - The macrocyclic antibiotic LY333328 has been evaluated as a chiral selector for
      the enantioseparation of nine dansylated amino acids. This macrocyclic
      glycopeptide was used as a chiral mobile phase additive (CMPA) in conjunction
      with narrow bore high-performance liquid chromatography (HPLC). The key mobile
      phase parameters of LY333328 concentration and buffer pH were varied, along with
      variations in stationary phases consisting of C8, phenyl, cyano, and silica.
      After observing and plotting changes in retention and resolution based on
      corresponding variation in these parameters, a better understanding of the
      behavior of this chiral selector was obtained. The pKa values of the dansyl amino
      acid analytes and LY333328 were measured and used to gain a better understanding
      of the microenvironment in which these enantioseparations occur. Optimized
      conditions resulted in the baseline separation of eight of nine dansyl amino
      acids.

PMID- 9914655
TI  - Application of the two-film theory to the determination of mass transfer
      coefficients for bovine serum albumin on anion-exchange columns.
AB  - The paper describes a method of simultaneous determination of the external and
      the solid-phase mass-transfer coefficients from frontal analysis data. The
      protein flux to the solid particles is determined from the slope of the
      breakthrough curve and the mass-transfer coefficients are determined by fitting
      the two-film model to the experimentally determined flux. The two-film model is
      compared with two apparent overall driving force models: the apparent overall
      mobile phase driving force model and the apparent overall solid-phase driving
      force model. The experiments show that the apparent overall driving force models
      fail to describe the flux correctly and this is substantiated by the theory.
      Results obtained with bovine serum albumin on the anion-exchange media Q HyperD,
      Source, and Poros show that the external film resistance is significant for
      Reynolds numbers less than one. The experimental Sherwood numbers are lower than
      expected and their dependence on the Reynolds number are much higher than
      expected.

PMID- 9914656
TI  - Comparison of protein adsorption isotherms and uptake rates in preparative cation
      exchange materials.
AB  - Adsorption isotherms and effective diffusivities of lysozyme in a set of six
      preparative cation-exchange stationary phases were determined from batch uptake
      data in a stirred vessel. Both a pore diffusion and a homogeneous diffusion model
      were used in estimating diffusivities, with the isotherms fitted to a non
      Langmuirian analytical isotherm equation. The capacities inferred from the
      isotherms are found to be correlated with the surface area accessible to
      lysozyme, the effective surface concentrations obtained being in agreement with
      values measured by different methods in various non-chromatographic systems. The
      pore diffusivities show systematic trends with protein and salt concentration,
      and effects of pore size and connectivity are also evident. Some trends in the
      homogeneous diffusivities are quite different to those in the pore diffusivities,
      but these differences largely disappear when the homogeneous diffusivities are
      rescaled to account for adsorption equilibrium behavior. Additional information
      is required to elucidate further the mechanisms of coupled diffusion and
      adsorption in stationary phases.

PMID- 9914657
TI  - Structural characteristics of low-molecular-mass displacers for cation-exchange
      chromatography. II. Role of the stationary phase.
AB  - The relative efficacy of a variety of low-molecular-mass displacers was examined
      on three different stationary phase materials. Several homologous series of
      displacer molecules were evaluated on these ion-exchange resins using a displacer
      ranking plot based on the steric mass action model. The results demonstrate that
      while aromaticity and hydrophobicity can play a significant role in the affinity
      of displacer molecules on polymethacrylate based and hydrophilized polystyrene
      divinylbenzene based materials, this effect is much less pronounced on an agarose
      based resin. The work presented in this paper demonstrates that different
      structural features of low-molecular-mass displacers can dominate their affinity
      on various stationary phase materials employed and provides rules of thumb for
      the design of high affinity, low-molecular-mass displacers for a variety of
      commercial cation-exchange materials.

PMID- 9914658
TI  - Comparison of loading capacities of various proteins and peptides in culture
      medium and in pure state.
AB  - Chromatographic media suppliers most frequently state the capacities of their
      gels based on either static capacities or frontal analysis experiments of pure
      proteins, however, these capacity values are often far from the capacities
      experienced in the production of such proteins. In this work static and dynamic
      capacities of various pure industrial proteins or peptides are compared to the
      capacities of the proteins or peptides under similar conditions in their natural
      culture medium. The results show a significant decrease in the static and dynamic
      capacities of the proteins or peptides when present in culture medium due to
      competitive binding of medium proteins. The proteins and peptides included in
      this study are: lipolase, glucagon-like peptide-1, truncated prothrombin, insulin
      precursor, and anti-Factor VII monoclonal antibody.

PMID- 9914659
TI  - Purification of monoclonal antibodies from ascitic fluid using preparative
      electrophoresis.
AB  - Four monoclonal antibodies (including Ig subclasses, G1, G2a, and G2b) were
      purified from murine ascitic fluid by a preparative electrophoresis system using
      a charge- and size-based strategy. Most of the smaller contaminating proteins
      were removed at pH 8.3 when the ascitic fluid was passed through a cartridge
      containing a separating membrane with a pore size of M(r) 100,000. After this
      single step, the immunoglobulin heavy and light chains were the only significant
      bands present when analysed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. A second step, involving electrophoresis at pH 6.4-7.5 depending
      on the antibody can be used to remove residual contaminants. For each of the
      antibodies tested, the recovery of activity at each step was over 80%. As this
      technology is directly scalable, purification of antibodies by the method
      described here could be considered a cost effective alternative to protein A
      chromatography.

PMID- 9914660
TI  - New approaches to the isolation of DNA by ion-exchange chromatography.
AB  - The performance of different anion-exchange media have been compared for the
      isolation of plasmid DNA and genomic DNA from bacterial cells and human whole
      blood. Whatman DEAE-Magarose, based on an agarose bead containing a paramagnetic
      component, has been compared with prepacked gravity-flow columns containing a
      derivatised silica matrix. In each case the DNA isolation at various scales of
      operation was similar both in terms of yield and quality. The magnetic
      susceptibility of DEAE-Magarose is very high, facilitating the use of this
      separation technique for rapid flexible batch chromatographic processes, a
      limitation of the prepacked column techniques.

PMID- 9914661
TI  - Development of attitude strength over the life cycle: surge and decline.
AB  - This article explores the relation of age to manifestations and antecedents of
      attitude strength. Three studies demonstrate that susceptibility to attitude
      change is greater during early and late adulthood than during middle adulthood.
      Three additional studies demonstrate that attitude importance, certainty, and
      perceived quantity of attitude-relevant knowledge are greater in middle adulthood
      than during early or late adulthood. These antecedents may therefore explain life
      cycle shifts in susceptibility to change. Susceptibility to change, importance,
      certainty, and perceived knowledge differ from one another in terms of their
      correlations with education, gender, and race, challenging the notion that
      attitude strength is a unitary construct. Evidence that people incorrectly
      believe that susceptibility to change declines steadily over the life course
      reinforces the distinction between operative and meta-attitudinal measures of
      attitude strength.

PMID- 9914662
TI  - The impact of negative affect on autobiographical memory: the role of self
      focused attention to moods.
AB  - Five studies examined how self-focused attention affects the impact of negative
      moods on autobiographical memory. It was proposed that self-focused attention to
      moods may increase the likelihood of both mood-congruent recall and mood
      incongruent recall and that the type of recall effect that occurs will depend on
      the manner in which people focus on their moods. In these studies, participants
      were led to experience negative or neutral moods, exposed to a manipulation
      designed to affect some aspect of their attention to their moods, and then asked
      to report memories. This research revealed that when people adopt a reflective
      orientation to their moods, they are more likely to engage in mood-incongruent
      recall; in contrast, when they adopt a ruminative orientation to their moods,
      they are more likely to engage in mood-congruent recall. Thus, the way in which
      people focus on their moods moderates the relation between mood and memory.

PMID- 9914663
TI  - Priming relational schemas: effects of contextually activated and chronically
      accessible interpersonal expectations on responses to a stressful event.
AB  - The authors used a relational schemas approach to test the effects of
      interpersonal expectations on responses to a stressful event. In Study 1, a
      subliminal priming technique was used to demonstrate the causal influence of
      experimentally activated interpersonal expectations on affect, support seeking,
      and coping responses to a hypothetical unplanned pregnancy. Activation of
      positive interpersonal expectations increased reports of seeking emotional
      support and decreased the use of self-denigrating coping. Activation of negative
      interpersonal expectations decreased reports of positive affect and tended to
      impede growth-oriented coping. Chronically accessible interpersonal expectations,
      assessed by an attachment questionnaire, were also associated with affect,
      seeking of support, and coping. Study 2 undermined the possibility that the
      experimental findings obtained with this priming procedure resulted from a mood
      manipulation.

PMID- 9914664
TI  - Through the looking glass darkly? When self-doubts turn into relationship
      insecurities.
AB  - The authors argue that individuals regulate perceptions of their relationships in
      a self-protective way, finding virtue in their partners only when they feel
      confident that their partners also see virtues in them. In 4 experiments, the
      authors posed an acute threat to low and high self-esteem individuals' feelings
      of self-worth (e.g., guilt about a transgression, fears of being inconsiderate or
      intellectually inept). They then collected measures of confidence in the
      partner's positive regard and acceptance (i.e., reflected appraisals) and
      perceptions of the partner. The results revealed that low self-esteem individuals
      reacted to self-doubt with heightened doubts about their partners' regard, which
      then tarnished impressions of their partners. In contrast, high self-esteem
      individuals reacted to self-doubts by becoming more convinced of their partners'
      continued acceptance, using their relationships as a resource for self
      affirmation.

PMID- 9914666
TI  - Unmasking a cognitive vulnerability to depression: how lapses in mental control
      reveal depressive thinking.
AB  - This research tested the idea that a cognitive vulnerability to depression can be
      concealed by thought suppression and revealed when cognitive demands undermine
      mental control. Depressive, at-risk, and nondepressive participants unscrambled
      sentences that could from either positive or depressive statements. Half of the
      participants also received a cognitive load. The results indicated that without a
      load, at-risk participants showed little evidence of depressive thinking,
      producing a similar rate of positive statements as did nondepressive individuals
      and a lower percentage of negative statements than did depressive participants.
      However, the cognitive load caused an increase in at-risk participants'
      production of negative statements, revealing a previously undetected tendency
      toward negative thinking that made them resemble depressive participants. As
      predicted, this effect was especially pronounced among individuals who routinely
      engaged in thought suppression.

PMID- 9914665
TI  - Motivations for sex and risky sexual behavior among adolescents and young adults:
      a functional perspective.
AB  - The implications of a functionalist perspective for understanding sexual risk
      taking are explored. Key motivational dimensions thought to underlie human
      behavior (viz., approach vs. avoidance, autonomy vs. relatedness) were used to
      identify 4 broad domains of sexual motivations and to develop a measure of
      specific motives within each of these domains. Data from both college student and
      community samples are used to demonstrate the psychometric adequacy of these
      scales and to show that having sex for different reasons predicts distinctive
      patterns of sexual risk taking both cross-sectionally and longitudinally: that
      selection into specific types of sexual relationships partially mediates these
      effects; and that these needs may be differentially expressed, or even
      suppressed, depending on relationship context. Results provide strong support for
      the functionalist perspective on behavior and indicate that an adequate
      understanding of sexual risk-taking behavior must take into account the various
      needs and goals that such behavior can serve.

PMID- 9914667
TI  - Effects of stressful daily events on mood states: relationship to global
      perceived stress.
AB  - This study used experience sampling methodology to examine the relationship
      between stressful daily events and mood. Eighty-five male white-collar workers
      completed self-reports 10 times a day for 5 days. Controlling for individual
      differences in mood levels, multilevel regression analyses showed that events
      were followed by increases in negative affect (NA) and agitation (Ag) and by
      decreases in positive affect (PA). More unpleasant events were associated with
      greater changes in all three mood dimensions; controllability mitigated the
      effects of events on NA and PA. Prior events had persistent effects on current
      mood. High perceived stress (PS) was associated with greater reactivity of NA and
      PA to current events, whereas trait anxiety moderated reactivity of Ag. Results
      indicate that PS is related not only to a higher frequency of reported events but
      also to more intense and prolonged mood responses to daily stress.

PMID- 9914668
TI  - Interpersonal forgiving in close relationships: II. Theoretical elaboration and
      measurement.
AB  - Interpersonal forgiving was conceptualized in the context of a 2-factor
      motivational system that governs people's responses to interpersonal offenses.
      Four studies were conducted to examine the extent to which forgiving could be
      predicted with relationship-level variables such as satisfaction, commitment, and
      closeness; offense-level variables such as apology and impact of the offense; and
      social-cognitive variables such as offender-focused empathy and rumination about
      the offense. Also described is the development of the transgression-related
      interpersonal motivations inventory--a self-report measure designed to assess the
      2-component motivational system (Avoidance and Revenge) posited to underlie
      forgiving. The measure demonstrated a variety of desirable psychometric
      properties, commending its use for future research. As predicted, empathy,
      apology, rumination, and several indexes of relationship closeness were
      associated with self-reported forgiving.

PMID- 9914669
TI  - Self-fulfilling prophecy and hypnotic response are not the same thing.
AB  - The authors used the "bogus-item" methodology originally used by C. Wickless and
      I. Kirsch (1989) to examine the effects of response expectancy manipulations on
      subjects' subsequently measured hypnotizability scores. The results of the first
      experiment failed to replicate Wickless and Kirsch's (1989) findings that
      surreptitious confirmation of suggested items (the bogus-item manipulation) leads
      to higher scores on subsequently measured hypnotic responsiveness. The second
      experiment tested if, in fact, response expectancies were enhanced by the bogus
      item manipulation, and the manipulation's effect on behavioral and subjective
      responsiveness to hypnosis was reexamined. A significant increase was found in
      response expectancies as a result of the bogus item expectancy manipulation, but
      again no evidence that this manipulation led to increased hypnotic responsiveness
      was found. Hypnotic responsiveness may not be as reactive to expectancy
      manipulations as previously claimed, and it is suggested that the notion of
      hypnotic responsiveness as a trait-like ability is viable.

PMID- 9914670
TI  - XXII International Congress of the International Academy of Pathology and 13th
      World Congress of Academic and Environmental Pathology. Nice, France, October 18
      23, 1998. Abstracts.

PMID- 9914671
TI  - Virulence factors of aeromonads--an emerging food borne pathogen problem.
AB  - Aeromonas spp. possess a number of virulence properties which are considered
      responsible for intestinal and extra-intestinal infections in human beings and
      also for a wide variety of infections in animals. The paper discusses current
      status of colonization and toxic factors of Aeromonas spp., especially in
      relation to food and biochemical markers. Future research needs are also
      identified.

PMID- 9914672
TI  - Giardia lamblia: in-vitro sensitivity to some chemotherapeutic agents.
AB  - The susceptibility of Giardia lamblia to eight chemotherapeutic agents was
      studied in vitro. The criteria of viability of the parasite was the ability of
      the parasite to attach to the coverslip surface in situ, and to multiply in drug
      free media on subcultures. The giardicidal and 50% inhibitory concentrations of
      each drug were measured. The activity of metronidazole in vitro was found to be
      similar to that of mepacrine, whilst that of chloroquine was inferior. The
      sensitivity of G. lamblia to mepacrine and chloroquine is markedly greater than
      that reported for Entamoeba histolytica.

PMID- 9914673
TI  - Brucellosis in north India: results of a prospective study.
AB  - Human brucellosis is a significant public health problem in India, the magnitude
      of which is not known. Paucity of clinico-epidemiologic data hampers control
      strategies. We prospectively studied 121 cases of fever of unknown origin (FUO)
      and 50 occupationally exposed individuals. Four patients with FUO had acute
      brucellosis (3.3%) while 8 (6.6%) had serological evidence of previous brucella
      infection. Seven of the 50 (14%) asymptomatic, 'at risk' individuals screened
      were seropositive for brucella. Persistence of the animal reservoir of infection,
      low physician awareness, poor availability of diagnostic facilities, and the non
      existence of regional data bases contribute towards the perpetuation of this
      zoonosis in India, while it has been eradicated from most developed countries.

PMID- 9914674
TI  - A retrospective serological survey of humans in India for Wanowrie virus.
AB  - Wanowrie virus (WAN) is an ungrouped arbovirus having morphogenetic characters in
      common with Bunyavirus. It was isolated for the first time from ticks, Hyalomma
      marginatum isacci (6700 strain) and subsequently from a human case (68923
      strain). In the absence of any reports on the prevalence of this virus amongst
      humans in India, 600 human sera were tested in the Complement Fixation (CF) test
      against both the strains of WAN virus. One hundred human sera were randomly
      selected from six different states, viz Jammu and Kashmir, Rajasthan, Orissa,
      Maharashtra, Karnataka and Tamil Nadu. CF antibodies were detected in 77 sera
      (12.8%) against the 6700 antigen while 91 sera (15.1%) possessed antibodies
      against the 68923 antigen; 60 sera were found to be reactive against both the
      antigens, with almost identical titres. There was no statistical difference in
      the distribution of CF reactive sera with respect to age, gender and geographic
      locations. All the CF reactive sera were found to be negative when tested in the
      neutralization test against the respective virus strains. The CF antibodies
      detected in these sera may have been produced during exposure to an antigenically
      closely related virus yet to be identified.

PMID- 9914675
TI  - 'Anti-malaria month'--a step forward in multisectoral collaboration and community
      involvement in malaria control.
AB  - For a long time malaria control in India has largely been a government
      responsibility with little involvement of the community at large, and other
      sectors of the economy in the control efforts. There is now increasing
      realisation that involvement of the community and a multi-sectoral approach
      should be essential components of the malaria control strategy. The National
      Malaria Eradication Programme is accordingly laying greater emphasis on
      coordination with other sectors of the economy, and changing community
      perceptions and health-related behaviour. A massive programme of community
      mobilisation with this objective in view has been taken up since 1997. A major
      component of this community mobilisation programme is the observance of an 'Anti
      Malaria Month', during which, country wide awareness campaigns are undertaken at
      all levels of implementation, to promote inter-sectoral collaboration and
      community action for malaria control. The present paper summarises the rationale
      and messages of the 'Anti-Malaria month'.

PMID- 9914676
TI  - Evaluation of laboratory techniques for diagnosis of amoebiasis.
AB  - Evaluation of 82 cases of amoebiasis including 4 of liver abscess was done.
      Microscopy of 62 stool samples revealed trophozoites in 19 (30.6%) and cysts in 8
      (12.9%). PVA preserved samples were stained by iron-hamatoxylin and trichrome.
      Twenty-nine samples (46.7%) were positive by culture on Endamoeba, NIH and
      Charcoal agar. Additional two culture positive cases were negative by direct
      microscopy. Three (75%) samples of liver abscess pus were culture positive. Of
      the sera screened for amoebic antibodies by ELISA, 13 (17.3%) were positive.
      Stool and blood of healthy controls and 25 gastroenteritis cases were similarly
      analysed. Of healthy controls one had a high ELISA titre.

PMID- 9914677
TI  - Knowledge, attitude and practices related to dengue in rural and slum areas of
      Delhi after the dengue epidemic of 1996.
AB  - To assess the knowledge and attitudes about dengue and practice of prevention
      followed by the residents of a rural area and an urban resettlement colony of
      East Delhi, an interview based cross sectional KAP study was undertaken in Jan 97
      to Feb 97, a few months after the dengue epidemic in rural area and urban areas
      of East Delhi. A pre-structured and pre-tested format containing the relevant
      questions was administered to the subjects. A total of 687 subjects (334 rural
      and 353 urban) were interviewed. Nearly four fifth (82.3%) of these were aware of
      Dengue. Audiovisual media was the most common source of information in both the
      areas. Knowledge about the disease was fair to good. Fever was the commonest
      symptom of the disease known to 92% urban and 83% rural respondents followed by
      symptoms of bleeding and headache. Mosquito was known to spread the disease to
      71% rural and 89% urban respondents. More than two third respondents in urban and
      two fifth in rural areas had used some method of mosquito control or personal
      protection during the epidemic.

PMID- 9914678
TI  - Detection of HIV seropositivity during an outbreak of Japanese encephalitis in
      Manipur.
AB  - An epidemic outbreak of Japanese encephalitis (JE) occurred during mid 1995.
      Sixteen serum samples from patients with history of febrile headache,
      convulsions, mental confusion, neck rigidity etc. were sent to the Department of
      Virology, School of Tropical Medicine, Calcutta, in August, 1995. Twelve (75%)
      showed HIV antibody against JEV. Out of these 12 sera showing HIV antibody titre
      between 1:40 and 1:160, eight (66.6%) showed IgM antibody, giving the presumptive
      diagnosis of recent JEV infection. Five of these 16 sera showed HIV
      seropositivity (31.25%). Concomitant JEV and HIV infection could be detected in 3
      cases. However, in 2 sera HIV titre were less than 1:20. This is probably the
      first documentation of concomitant JEV and HIV infection in the eastern India.

PMID- 9914679
TI  - Early development of acute filariasis in a migrant from non-endemic to hyper
      endemic area: a case report.
AB  - A case report of a European woman who contracted filariasis after staying for a
      few weeks in a filaria endemic area of south India is presented in this paper.

PMID- 9914680
TI  - Anonymous testing of HIV infection in pregnant women.

PMID- 9914681
TI  - Pictorial key to the common Indian species of Aedes (Stegomyia) mosquitoes.
AB  - The paper provides a simple pictorial key to differentiate common stegomyia
      species found in urban areas. This key will help medical officers and paramedical
      staff in demarcating the areas of influence of Aedes aegypti within a Dengue
      surveillance area.

PMID- 9914682
TI  - Some epidemiological characteristics of Japanese encephalitis in Haryana state of
      northern India.

PMID- 9914683
TI  - As polio retreats, viruses in labs pose biggest risk to world population.

PMID- 9914685
TI  - Seasonal variation in molluscicidal activity of Solanum nigrum L.
AB  - Solanum nigrum L. leaves and fruits were shown to have molluscicidal activities
      against snails transmitting schistosomiasis and fascioliasis. In the present
      study, their molluscicidal activity against adult Biomphalaria alexandrina snails
      was assessed to determine whether plants collected at various seasons would have
      different degrees of toxicity. Leaves and fruits of three S. nigrum varieties
      were collected from Faiyoum and/or Giza during the four seasons. Leaves collected
      in autumn had the highest effect (LC50-35.4) followed by spring (LC50 = 44.36),
      summer (LC50 = 46.7) and winter (LC50 = 100.4). Toxicity of plant extracts was
      also affected by other seasonal dependent factors. These are the duration of
      plant exposure to direct sunlight and the size of the fruits. S. nigrum (black
      fruits) was more toxic (LC50 = 18.1) than the other two types, S. nigrum v.
      vellosum (yellow fruits) (LC50 = 38.9) and S. nigrum v. juidaicum (red fruits)
      (LC50 = 34.7).

PMID- 9914684
TI  - Role of anti-Trichinella spiralis antibodies and interferon-gamma in the
      protection against the enteral phase of experimental trichinosis.
AB  - Expulsion of adult Trichinella spiralis is the result of a complex
      immunologically mediated response. Experiments in mice demonstrated that IFN
      gamma, released by mesenteric lymph nodes (MLN) during infection play a major
      role. However, the role of mucosal and serum antibody responses is thought to be
      limited. Working on the intestinal phase, this study investigated, the role
      played by antibodies, transferred from vaccinated infected animals, in the immune
      response in comparison to that obtained by IFN-gamma administration. Transfer of
      antibodies gave 82.7% protection, while IFN-gamma in a dose of 1 x 10(4) U gave
      98.4% protection. The use of half the previous dose induced a protection of
      58.3%. These data indicate that vaccination followed by infection could generate
      antibodies capable of producing a protective immune response against the
      intestinal phase of T. spiralis. This reached a level near to that obtained by
      IFN-gamma administration.

PMID- 9914686
TI  - Rate of reinfection with S. mansoni following treatment in two newly reclaimed
      areas of Egypt.
AB  - This paper reports an on-going study in two newly reclaimed areas in Ismailia
      Governorate, El-Manayef, 10 km south-west of the city of Ismailia (area 1) and
      the other in Siani Peninsula, just east of the Bitter Lakes (area 2). In he
      baseline survey, the prevalence of infection of 49.9% and 40.1% and high
      intensity infection of 21.8% and 15.7% were found for S. mansoni in areas 1 and 2
      respectively. Geometric mean egg counts for those found positive were 101.2 and
      75.9. In a subsequent survey, a year after treatment of positives, the overall
      prevalence was 30.2% and 30.5% and the prevalence of high intensity infection was
      8.6% and 10.5% in the two areas. The prevalence among those found positive and
      then treated during the first round (reinfection rate) was 31.7% and 19.2%.
      Geometric mean egg counts had declined from 141.3 to 63.1 and from 133.6 to 59
      among those who were reinfected. The occurrence of reinfection was strongly
      associated with younger age in both areas. Rates of reinfection showed a strong
      but not significant association with male sex in area 2 (p = 0.087), but no
      association in area 1. These high rates of reinfection demonstrate the importance
      of promotion of hygiene behaviors as well as ensuring access to chemotherapy.

PMID- 9914687
TI  - Effect of bioresmethrin on mitochondrial ultrastructure and oxidative
      phosphorylation in the flight muscles of Chrysomya albiceps (Wied.) (Diptera:
      Calliphoridae).
AB  - The sublethal effect of bioresmethrin on the ultrastructure, oxidation and
      phosphorylation of flight muscle mitochondria in the blow fly Chrysomya albiceps
      which survived treatment of newly formed pupae (0-day old) with 10
      micrograms/pupa (LD30) was studied. The ultrastructure of the flight muscle
      mitochondria was severely deteriorated by treatment with bioresmethrin. The
      deterioration included disalignment and sometimes destruction of the cristae and
      vacuolation of mitochondria. The oxidation rate was decreased in treated flies,
      although the P/O ratio was increased. The present study may indicate that
      bioresmethrin is neither an uncoupler nor a direct inhibitor of oxidative
      phosphorylation but may have functioned as an inhibitor of the oxidation rate.

PMID- 9914688
TI  - Spinal cord hydatid cysts in Egypt.
AB  - Hydatid cysts or hydatidosis is a cyclozoonotic parasite, where dog is the
      definitive host and man is an incidental intermediate host. Human hydatid cysts
      have been encountered in many organs but the most prevalent is the liver followed
      by the lung. In this paper, we report for the first time spinal cord hydatid
      cysts in two preparatory school pupils. They were presented with sever back pain,
      bilateral neurologic deficient in both lower limbs including motor and sensory
      affection in scattered pattern as well as knees reflux. The two cases were
      diagnosed hydatidosis by surgical removal of the cysts and confirmed by
      histological and parasitological examinations. It is concluded that parasitic
      infection in the spinal cord is rare but it should be in mind with disseminating
      parasite(s).

PMID- 9914689
TI  - A nematode parasite from the lung of mynah birds at Jeddah, Saudi Arabia.
AB  - Twelve mynah birds (Gracula species) were collected dead from Jeddah market. The
      immediate parasitological examination of all organs revealed only helminth
      infection in the lungs and air sacs with five to eight female worms of the
      nematode; Diplotriaena divergens. The role of the locusts in disseminating
      infection in Saudi Arabia was discussed.

PMID- 9914690
TI  - Histochemical and pathological studies on biopsied materials from patients with
      Ancylostoma duodenale infection.
AB  - Ancylostoma duodenale is still the dominant hookworm species in the Mediterranean
      area, India, China and Japan. In the present study, biopsied materials were taken
      from the small intestine of 30 patients infected only with A. duodenale and 12
      cross matched controls. The results showed some pathological changes in severely
      infected cases. However, normal or insignificant changes were seen in the
      enzymatic activity of the intestinal mucosa.

PMID- 9914691
TI  - Studies on hydatidosis in slaughtered camels in Egypt.
AB  - Hydatid cyst or hydatidosis is a cyclozoonotic parasite of worldwide
      distribution. Human and animal cases have been reported in Egypt by many authors.
      Also, the tape worm Echinococcus granulosus has been reported in stray dogs. The
      present work studied hydatidosis in 400159 camels imported from Sudan over five
      years (1992 to 1996) and slaughtered in governmental abattoirs under the
      supervision of GOVS. The overall annual prevalence rates of camel infection were
      5.5% (1992), 6.1% (1993), 6.7% (1994), 8.2% (1995) and 4.3% (1996). The most
      predicted site of infection was the lung followed by the liver. Cystic infection
      in other organs were rarely seen. The fertility of the cysts was 29% and 20% in
      lung and liver respectively. Macroscopic and microscopic studies of some
      interesting cysts were done. No doubt, hydatidosis is a public health problem
      that affects also the human welfare and economy. The preventive and control
      measures for man and animal were discussed.

PMID- 9914692
TI  - Effect of some stressors on pathogenicity of Eimeria tenella in broiler chicken.
AB  - The present investigation was carried out to study the effect of stress on
      severity of Eimeria tenella infection in chickens. Stressors applied were
      vaccination and crowdness. One hundred and twenty five one-day old chicks were
      divided into five groups. The groups were as follow: group (1) control negative,
      group (2) control positive, group (3) crowded non-vaccinated, group (4)
      vaccinated, and group (5) vaccinated crowded. The chicks of 2-5 groups were
      inoculated with 10 x 10(3) sporulated oocysts of E. tenella per chick at 3rd day
      old, then challenged with 15 x 10(3) sporulated oocysts of E. tenella on day 28.
      The results revealed that, the highest mortality percent, oocysts production and
      caecal scores were recorded in the crowded vaccinated group. This group also
      exhibited the lowest weight of body, spleen, bursa and thymus. At the last four
      weeks, it was found that overstocking of chickens lead to elevation of
      corticosterone levels. Total proteins, glucose, calcium and phosphorus levels
      decreased in crowded vaccinated group.

PMID- 9914693
TI  - Studies on coccidia species of genus Eimeria from domestic rabbit (Oryctolagus
      cuniculus domesticus L.) in Jeddah, Saudi Arabia.
AB  - Five Eimeria species were reported from domestic rabbits (Oryctolagus cuniculus
      domesticus L.) caught from Jeddah, Saudi Arabia. According to their prevalences,
      they were: Eimeria perfarans (65%), E. magna (45%), E. stiedae (25%), E. exigua
      (20%) and E. piriformis (10%). 90% of the examined rabbits were positive and
      mixed infection with two or three Eimeria species was most frequent. E. stiedae,
      E. piriformis and E. exigua were identified and recorded for the first time from
      rabbits in Saudi Arabia and are considered as new locality or geographical
      distribution.

PMID- 9914694
TI  - The larvicidal activity of solvent extracts of three medicinal plants against
      third instar larvae of Chrysomyia albiceps.
AB  - Four solvent extracts of each of Lemongrass (Symbopogon citratus), Santonica
      (Artemisia cinae) and Pomegranate (Punica granatum) were tested against the 3rd
      instar larvae of Chrysomyia albiceps. The pomegranate extracts showed the
      larvicidal activity with LC50 ranging between 25 ppm (acetone extract) and 280
      ppm (chloroform extract). The Santonica showed larvicidal activity with LC50
      ranging between 48 ppm (ethanol extract) and 380 ppm (acetone extract). The
      Lemongrass showed activity with LC50 ranging between 135 ppm (ethanol extract)
      and 570 ppm (chloroform extract). So, the most effective action in accordance to
      LC50 were the acetone extract of pomegranate, followed by ethanol extract of
      Santonica and lastly ethanol extract of Lemongrass. The slope functions of these
      three extracts were 4.6, 2.8 and 8.22 respectively. The shift to insect control
      by plant extracts pave the way to a somewhat healthy environment.

PMID- 9914695
TI  - A monoclonal antibody diagnoses active Fasciola infection in humans.
AB  - Monoclonal antibodies (MABs) were produced after fusion of spleen cells of
      Fasciola antigen immunized BALB/c mice and non secreting murine myloma cells
      (P3x63 Ag8). Six MAbs, showing the highest reactivity with purified Fasciola
      antigen, were prepared. All 6 MABs were IgG2 with Kappa light chain. Reactive
      epitopes recognized by the six MAbs were glycoprotein in nature, and each MAb
      recognized a single epitope of Fasciola antigen. No cros reactions were observed
      with Schistosomal AWSA, hydatid Ag and Entamoeba Ag. EITB technique showed a
      specific diagnostic band at 17.5 kDa for each of the six MAbs. Anti-Fasciola MAb
      (AD2) was conjugated with peroxidase and was used with anti-rabbit anti-Fasciola
      polyclonal antibody in sandwich-ELISA to detect circulating Fasciola antigen in
      serum and urine samples of 57 fascioliasis patients, 51 schistosomiasis patients,
      45 patients infected with other parasites and 47 healthy controls. Sensitivity of
      the assay in detection of circulating Fasciola antigen in sera and urines of
      Fasciola infected patients was 100%. The specificity of the assay was calculated
      among patients infected with schistosomiasis and other parasites and was 98% in
      serum and 97% in urine. A positive correlation was found between levels of
      circulating Fasciola antigen in serum and urine samples of fascioliasis patients
      (r = 0.825, p < 0.05).

PMID- 9914696
TI  - Detection of Microsporidia by different staining techniques.
AB  - Previous detection of Microsporidia relied mainly on electron microscopy and
      histopathology. Recently, non invasive methods were able to recognize this
      microorganism. In the present study, different stains were used as a means of
      diagnosing spores of Microsporidia in stool samples of immunosuppressed patients.
      The original modified trichrome stain (MTS) was used as a standard screening
      technique for all stool samples. Positive samples for Microsporidia were then
      stained with the trichrome blue stain, Didier's trichrome blue stain, acid-fast
      trichrome stain (AFT), modified Ziehl-Neelsen stain, giemsa stain and calcofluor
      white M2R stain. Both calcofluor and the AFT stains were most efficient. They
      could simultaneously detect coccidial oocysts and microsporidial spores. This is
      beneficial and time-saving in the diagnosis of stool samples of immunosuppressed
      patients, which usually contain more than one opportunistic protozoon. Both
      stains are easy to perform and require the least amount of staining and
      examination.

PMID- 9914697
TI  - Evaluation of specific immunoglobulin G avidity enzyme linked immunosorbent assay
      (IgG avidity ELISA) in diagnosis of early and chronic Schistosomiasis mansoni.
AB  - This work was performed to study variations of Schistosoma specific
      immunoglobulins between early and chronic schistosomiasis mansoni in both
      children and adults. A modified enzyme linked immunosorbent assay (ELISA), based
      on dissociation of antigen antibody complexes with 8 mol/L urea (8 M urea)
      solution, was used to measure levels of low avidity immunoglobulin G antibodies
      (IgG Abs) against Schistosoma mansoni soluble egg antigen (SEA). The study
      included eighty (80) patients with active mansonian schistosomiasis. They were
      classified according to age, history, clinical symptomatology and examination and
      direct parasitological methods of diagnosis into early and chronically infected
      children and adults. Sera of all patients were subjected to: ELISA measuring
      Schistosoma specific IgM and IgG., immunoglobulin G (IgG) avidity ELISA and
      indirect haemagglutination test (IHA). Schistosoma specific IgG avidity ELISA
      detected higher levels of both urea IgG inhibition percentage and low avidity IgG
      Abs in early cases of schistosomiasis than chronic ones in both children and
      adults. Levels of urea IgG inhibition percentage were higher in children than
      adults. Schistosoma specific IgM/IgG ratio was more than one (> 1) in early cases
      in both children and adults and less than one (< 1) in chronic cases in children
      and 70% of adults. IHA titres were statistically higher in chronic cases than
      early ones in children only. So, it can be concluded that IgG avidity ELISA is a
      valuable method that helps to differentiate early from chronic schistosomiasis
      mansoni infection in both children and adults.

PMID- 9914698
TI  - Study and characterization of different developmental stages of Leishmania major.
AB  - The complete developmental cycle of Leishmania major in axenic culture was
      achieved by simply changing the temperature whether sudden from 22 degrees C to
      37 degrees C or stepwise 22 degrees C, 29 degrees C and then 37 degrees C. The
      morphology by light microscopy, GPI isoenzyme pattern and PCR amplification of
      minicircle of kinetoplast DNA of the different stages were studied. The
      amastigotes obtained from the foot pads of mice were compared to those obtained
      from axenic culture. The GPI isoenzyme pattern and the PCR amplification products
      showed distinct differences between the promastigotes and the amastigotes. The
      amastigotes of the two sources also showed differences after temperature changes.

PMID- 9914699
TI  - Protozoal parasites in tick species infesting camels in Sinai Peninsula.
AB  - A faunistic survey of ticks infesting camels was carried out in 7 localities of
      Sinai; El-Arish, Beer El Abd, Nakhel, Ain Mousa, St. Catherine, Wadi Hadra, and
      Dahab. The protozoal organisms present in the gut and haemolymph of the collected
      tick species were investigated. Results revealed the presence of six species of
      tick infesting camels, Hyalomma dromedarii, H. impeltatum, H. an. excavatum, H.
      an. anatolicum, H. marginatum and H. schulzei. The first 3 species were most
      common, whereas the latter 3 species were found in certain limited localities.
      Babesia sp. and Theilera sp. were recorded in both tick guts and haemolymph in
      most species allover the studied areas. Trypanosoma sp. was recorded in the guts
      of ticks collected from Beer El Abd, Nakhel and Dahab. Anaplasma sp. was found in
      tick guts from Beer El Abd and Dahab, however the same organism was detected in
      the haemolymph of ticks collected in Nakhel and Dahab.

PMID- 9914701
TI  - Liver tissue schistosomiasis mansoni vaccine, as a third generation livestock
      immunogenes.
AB  - Liver tissue of Schistosoma mansoni-infected hamsters has been tried to immunize
      white mice against Schistosoma mansoni infection. A saline suspension of liver
      tissue of infected hamsters was prepared and given subcutaneously in the ventral
      aspect of the abdominal wall to the right of the umbilicus. The present study
      proved that the used vaccine has a protective role in reducing the morbidity and
      mortality of the disease.

PMID- 9914700
TI  - The relation between scabies and hypersensitivity to antigens of house dust mites
      and storage mites.
AB  - Twenty five non-atopic scabietic patients were examined to estimate their
      reaction to crude house dust mite Dermatophagoides farinae (D. farinae) and
      storage mite Tyrophagus putrescentia (T. putrescentiae) antigens. Skin prick
      testing (SPT) by extracts of both mites antigens showed significant higher
      positive results in scabietics when compared to non-scabietic control subjects.
      Moreover, 60% and 56% of scabietic patients showed positive levels of specific
      anti-D. farinae and T. putrescentia IgE respectively in comparison to 13.4% & 20%
      of control subjects. A significant difference has been obtained when the total
      number of positive results were compared to the total number of negative ones.
      The results revealed that there is an evidence of cross reactivity between
      Sarcoptes scabiei antigens and extracts of D. farinae and T. putrescentiae, and
      the hypersensitivity to house dust mite and storage mite antigens was
      significantly higher in scabietics than in controls. It could be concluded that
      there is some proof that other mites rather than Sarcoptes scabiei may have a
      role in the pathogenesis of scabies and the cross reactivity between S. scabiei
      and house dust mite and storage mite may explain the persistence of symptoms in
      some cases even after proper treatment of the disease.

PMID- 9914702
TI  - Electroencephalographic changes in rats received antigens of different parasites.
AB  - The prevalence of epilepsy in developing countries is much higher than in
      developed ones. Some of the highest prevalence rates in developing countries have
      been reported from tropical Africa where parasitic infections are endemic. This
      work was carried out to assess the effect of different parasitic antigens on the
      activity of cerebral cortex in rats. Nine crude antigens were used: Adult
      Fasciola, adult S. mansoni, hydatid cyst, T. spiralis, E. histolytica,
      Acanthamoeba spp. G. lamblia, Cryptosporidium spp. and crude antigen of T.
      gondii. All the parasitic antigens induced electroencephalographic changes
      compared with baseline tracings.

PMID- 9914703
TI  - Preliminary identification of an intestinal coccidian parasite in man.
AB  - An unidentified coccidian parasite was observed in saline faecal smears of five
      immunocompromised patients. Very few of these organisms were observed in the
      oocystic stage. They were oval in shape with rounded edges and contained two
      sporulated sporocysts, 7.5-9.5 um in diameter with a nipple like projection. They
      are smaller than sporocysts of Sarcocystis hominis and suihominis. For further
      identification, the modified Ziehl-Neelsen stain was used. The sporocysts showed
      variability in staining. Most of them were unstained while those stained were
      more or less rounded with well defined four crescent shape sporozoites and a
      residual body but with an unstained cyst wall. Sporocysts were positively stained
      by phenol auramine which had the advantage of staining the cyst wall. Other
      coccidial parasites encountered in this study were Cryptosporidium parvum
      (18.2%), Cyclospora cayetanensis (1.8%) and Isospora belli (0.9%) they were
      differentiated from this organism. SEM showed oval sporocysts with thickened
      ridges on its surface dividing it into plates which is a characteristic feature
      of the family Sarcocystidae. From the above characters, the features of this
      parasite is suggested to be a Sarcocystis like Protozoa.

PMID- 9914704
TI  - Rodents, their seasonal activity, ecto- and blood-parasites in Saint Catherine
      area, South Sinai Governorate, Egypt.
AB  - Rodents are on the top of animal reservoirs of zoonotic parasites. Five species
      of wild rodents were trapped on monthly base from Saint Catherine area. The
      highest trap index was 0.5 in May and the lowest was zero in December, January
      and February. The dominant rodents were Acomys c. dimidiatus followed by
      Dipodillus d. dasyurus and then A. r. russatus. Sporadic numbers of Sekeetamys c.
      calurus (3) and Eliomys. qu. melanurus (2) were collected. The ectoparasites in a
      descending order of abundance were mites (45.6%), lice (30.3%) and then fleas
      (24.1%). The most abundant ectoparasites among the three groups were Polyplax
      spinulosa (lice). Allodermanyssus sanguineus (mites), and Xenopsylla dipodilli
      (fleas). Leishmania amastigotes and Babesia microti were detected in Acomys.
      Also, one pregnant female A. c. dimidiatus was infected with a nematode parasite,
      Syphacia obvelata. The results were discussed on the light of the previous work.

PMID- 9914705
TI  - Evaluation of ELISA, IFAT and trichinoscopy in experimental trichinosis:
      comparing larval antigens prepared from rat and pig muscles.
AB  - Two antigens were prepared, the first one was crude larval antigens derived from
      pigs and rats. The two antigens were tested by the enzyme linked immunosorbent
      assay (ELISA). The 2nd one, was two cuticular larval antigens derived from pigs
      and rats and were tested by the indirect immunofluorescent antibody test (IFAT).
      Both tests were used to evaluate the sensitivity and specificity of these
      different antigens. Serum samples from infected rats and pigs were tested with
      different antigens by ELISA and IFAT. At the end of experiment, all animals were
      killed and use trichinoscopy to reveal sensitivity and specificity versus ELISA
      and IFAT.

PMID- 9914706
TI  - Studies on culicini larvae in Mansoura Center, Dakahlia Governorate, Egypt.
AB  - Culicini larvae were collected from different water bodies in Mansoura Center,
      mainly Awish El Hagar, Gedilah, Mansoura City, Meet Badr Khames and Sandoub. Ten
      species of culicini larvae were collected. They were Culex adairi, Cx.
      antennatus, Cx. deserticola, Cx. pusillus, Cx. pipiens, Cx. univittatus, Aedes
      caspius, Ae. detritus, Culiseta longiareolata and Uranotaenia uniguiculata. The
      most common larvae in descending order were those of Cx. univittatus, Cx.
      antennatus and Ae. caspius. The highly infected area was Meet Badr Khames and the
      least was Mansoura city. The highly infested water body was the canals and the
      least was the sewage wells. Rice fields were only infested with Cx. antennatus (P
      > 0.05). The whole results were discussed.

PMID- 9914708
TI  - Compatibility of Biomphalaria alexandrina, Biomphalaria glabrata and a hybrid of
      both to seven strains of Schistosoma mansoni from Egypt.
AB  - The susceptibility of Biomphalaria alexandrina, Biomphalaria glabrata and a
      hybrid snail of both, all obtained from natural habitats in Egypt, to infection
      with six human local strains of Schistosoma mansoni and a laboratory strain of
      human origin was determined. The infection rate, prepatent period, periodic
      cercarial production and duration of cercarial shedding were compared in all
      cases. The results showed that each of the three studied Biomphalaria snails had
      different rates of infection and different values of total periodic cercarial
      production with various strains of S. mansoni. However, the mean infection rate
      of all local S. mansoni strains was significantly much higher in B. alexandrina
      than each of B. glabrata and the hybrid snail, being 66%, 7.2% and 8.5%,
      respectively. Considering the mean of results of all local S. mansoni strains
      used, the longevity of cercariae-shedding B. glabrata and the hybrid snails was
      much longer than that of B. alexandrina, with high significant difference between
      them (P < 0.01), being 94.5, 103.3 & 69.1 days, respectively. The mean prepatent
      period of various S. mansoni strains showed no significant difference in the
      three Biomphalaria snails studied. The hybrid snail produced periodically (1 h
      stimulant twice weekly) more schistosome cercariae/snail (4,784.2) than B.
      glabrata (2,913.4 cercariae/snail) and the least production was in the case of B.
      alexandrina (1,397.2 cercariae/snail) (P < 0.05). The diurnal pattern of S.
      mansoni cercarial shedding was found to be similar for B. glabrata, B.
      alexandrina and the hybrid snail showing a peak of cercariae at the same time (9
      10 a.m.).

PMID- 9914707
TI  - Some studies on the growth and development of Echinococcus granulosus, camel
      origin in experimentally infected dogs.
AB  - Development of Echinococcus granulosus of camel subspecies in 35 experimentally
      infected dogs was performed at 3, 7, 10, 13, 18, 23, 35 and 56 days post
      infection (d.p.i.). Morphological characters of each developmental stage was
      studied and discussed. Generally, the results indicate that the segmentation
      firstly appeared at 18 d.p.i. Also, male and female genitalia could be detected
      at the same period. However, completely developed of genitalia appeared at 56
      d.p.i. Histological examination of small intestine of experimentally infected
      dogs revealed that the parasites were found in distended and thin wall crypts of
      Liberkuhn at 3, 7, & 10 d.p.i, while the parasite scolices were found embedded in
      the mucosa at 13, 18 & 23 d.p.i. No significant pathological changes were
      encountered in both infected and control dogs. This is the first report of
      strobilar development of E. granulosus of camel origin in experimentally infected
      dogs.

PMID- 9914709
TI  - Light and electron microscope studies of Hepatozoon mehlhorni, Bashtar et al.,
      1991 (Adeleina, Eucoccidiida) naturally infecting the viper Echis carinatus.
AB  - Light and electron microscopy have been used to study blood stages of H.
      mehlhorni as well as different developmental stages of the parasite within lung
      tissues of the naturally infected vipers Echis carinats captured from Siwah
      Oases, Egypt. A natural infection rate of 60% was recorded among vipers. Two
      types of meronts were observed within the endothelial cells of the viper's lung.
      The first type is the small one, produced 6-15 merozoites. The second type is the
      large one, produced 20-40 merozoites. In both types of meronts, merozoites were
      developed through an ectomerogenous manner. The erythrocytic parasites and the
      merozoites within the endothelial cells of the viper's lung sharing all general
      architecture of the apicomplexa. Moreover, evident peculiarities of
      haemogregarines were recorded, such as the presence of micronemes and rhoptries
      on both sides of the parasite nucleus, and the presence of large number (up to
      100) of subpellicular microtubules and micronemes (up to 150).

PMID- 9914710
TI  - Blood parasites of five species of lizards trapped in Abha Province, Saudi
      Arabia.
AB  - Five species of lizards, Agama yemenensis, A. adramitana, Chamaeleo chamaeleon,
      C. calyptratus and Acanthodactylus baskinaus were trapped alive from Abha
      Province. Serological and parasitological examinations of blood revealed
      antibodies against toxoplasmosis and leishmaniasis. Blood films showed Hepatozoon
      spp. The results were discussed with reference to their role as reservoir hosts.

PMID- 9914711
TI  - A study on secretory IgA in malnourished children with chronic diarrhoea
      associated with parasitic infections.
AB  - Fifty infants and children of both sexes (6-36 months) were divided into three
      groups (gp I) 20 malnutrition with chronic diarrhoea, (gp II) 20 malnutrition
      without diarrhoea and (gp III) cross matched control. In gp I, 75% showed
      parasitic infections with a significant increase in serum IgA (133.7 +/- 18.9) as
      compared to gp II (P < 0.001). Mean concentration of IgA was 4.87 +/- 1.24. In gp
      II, 20% showed parasitic infections with a non significant increase in serum IgA
      (115.8 +/- 14.2) as compared to gp III. The mean urinary secretory IgA was 4.87
      +/- 1.24, 1.12 +/- 0.325, and 1.44 +/- 0.35 respectively. There was more or less,
      no significant correlation between urinary secretory IgA and serum IgA level in
      the three groups.

PMID- 9914712
TI  - Schistosomiasis in newly reclaimed areas in Egypt. 1-distribution and population
      seasonal fluctuation of intermediate host snails.
AB  - Two newly reclaimed areas located west & east of Suez Canal, namely El Manayef
      area and El Morra area, were studied for patterns of distribution and population
      seasonal fluctuation of Biomphalaria alexandrina and Bulinus truncatus, the
      intermediate host snails of Schistosoma mansoni and S. haematobium, respectively.
      In this study Geographic Information System (GIS) techniques were utilized for
      producing maps and analyzing the results. Habitats of the two vector snail
      species were categorized into suitability levels depending on the frequency with
      which snails were collected over a 12 months period. Data obtained from the most
      suitable habitats were only used for studying the seasonal fluctuation of snail
      population. The results showed that both study areas were almost similar in major
      physico-chemical parameters. However, oxygen content in canals was higher than in
      drains and conductivity was higher in drains than in canals. As regards snail
      distribution and density, most snails of both considered species were clustering
      in much fewer numbers of sites, more pronouncedly in the case of Biomphalaria
      than Bulinus. Population density of snails was significantly higher in El-Manayef
      area than in El-Morra area and in canals than in drains. Both species exhibited 2
      population peaks/year, the peaks of Biomphalaria were in March-April & August in
      both study areas, while for Bulinus these peaks occurred in March-May and August
      in El-Manayef area and in May and March, respectively, in El-Morra area.

PMID- 9914713
TI  - Cell mediated immune response in chronic liver diseases: schistosomal, viral and
      neoplastic.
AB  - Cell mediated immune response (CMIR) was studies in 120 patients having chronic
      liver diseases. Patients were divided into 6 groups, (20 each). (1) Early
      hepatosplenic Schistosomiasis. (EHSS), (2) Late hepatosplenic Schistosomiasis.
      (LHSS), (3) Hepatosplenic Schistosomiasis with hepatitis B and/or C infections,
      (4) Hepatitis B virus cases. (HBV), (5) Hepatitis C virus cases (HCV), (6)
      Hepatocellular carcinoma cases. (HCC). Twenty within normal subjects taken as
      controls. Laboratory investigations revealed significant esinophilia in patients
      of group (1), haemoglobin level was significantly reduced in patients of group
      (1, 2, 3, & 6), serum albumin was significantly reduced in group (2). The
      percentage of positivity of skin testing using purified protein derivative,
      ranged between 10% of patients with LHSS, HBV, HCC and HSS with HBV and/or HCV,
      20% of patients with HCV and 25% of patients with EHSS. Percentage of positivity
      in control group was 100%. The mean diameter of delayed intradermal reaction (2.2
      +/- 0.5-6.1 +/- 2.1 mms.) was significantly lower in patients than controls. The
      response of lymphocyte transformation test to phytohaemmagglutinin was
      significantly lower in patients when compared to controls. The association of HBV
      and/or HCV with hepatosplenomegaly was accompanied with a marked depression in
      cell mediated immune response. Anaemia, hypoalbuminemia and nutritional status of
      the patients with chronic liver diseases play a major role in the suppression of
      cell mediated immune response.

PMID- 9914714
TI  - The first case report of suspected human dirofilariasis in the eyelid of a
      patient from Alexandria.

PMID- 9914715
TI  - GABAC receptors mediate slow membrane potentials in neurons of the rat major
      pelvic ganglia.
AB  - Effects of gamma-aminobutyric acid (GABA) on the neuronal membrane of the rat
      major pelvic ganglia (MPG) were studied using intracellular recording techniques,
      in vitro. Application of GABA (100 microM) to MPG neurons induced a
      depolarization (GABAd) associated with a decreased membrane input resistance and
      a slow hyperpolarization (s-GABAh) associated with an increased membrane input
      resistance. The GABA depolarization had two phases, a fast depolarization (f
      GABAd) and a subsequent slow depolarization (s-GABAd). Bicuculline (60 microM)
      blocked the f-GABAd but not the s-GABAd and s-GABAh. Picrotoxin (100 microM)
      blocked all the GABA responses. Imidazole-4-acetic acid (I4AA, 100 microM), a
      GABAc receptor antagonist, depressed the s-GABAd and s-GABAh, but did not block
      the f-GABAd. Cis-4-aminocrotonic acid (CACA), a GABAc receptor agonist, produced
      a depolarization followed by a hyperpolarization in MPG neurons. I4AA (100
      microM) depressed the CACA-induced responses. It was concluded that GABAA
      receptors mediate the f-GABAd and that GABAc receptors mediate the s-GABAd and s
      GABAh, in neurons of the rat MPG.

PMID- 9914716
TI  - Effects of 5-hydroxytryptamine on neuronal activities in the rat dorsolateral
      septal nucleus.
AB  - The ionic channels and signal transduction pathways underlying the 5
      hydroxytryptamine (5-HT)-induced hyperpolarization in neurons of the rat
      dorsolateral septal nucleus (DLSN) were examined by using intracellular and
      voltage-clamp recording techniques. Application of 5-HT (1-50 microM) caused a
      hyperpolarizing response associated with a decreased membrane resistance in DLSN
      neurons. The hyperpolarization induced by 5-HT was blocked by Ba2+ (1 mM) but not
      by tetraethylammonium (TEA, 3 mM), glibenclamide (100 microM) and extracellular
      Cs+ (2 mM). 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT; 3 microM), a
      selective agonist for the 5-HT1A receptor, mimicked 5-HT in producing the
      hyperpolarization. The 5-HT hyperpolarization was blocked by NAN-190 (5 microM),
      a 5-HT1A receptor antagonist. CP93129 (100 microM), a 5-HT1B receptor agonist,
      and L-694-247 (100 microM), a 5-HT1B/1D receptor agonist, also produced
      hyperpolarizing responses. The order of agonist potency was 8-OH-DPAT >> CP93129
      > or = L-694-247. (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI, 100
      microM), a 5-HT2 receptor agonist, and RS67333 (100 microM), a 5-HT4 receptor
      agonist, caused no hyperpolarizing response. The voltage-clamp study showed that
      5-HT caused an outward current (I5-HT) in a concentration-dependent manner. I5-HT
      was associated with an increased membrane conductance. I5-HT reversed the
      polarity at the equilibrium potential for K+ calculated by the Nernst equation.
      I5-HT showed inward rectification at membrane potentials more negative than-70
      mV. Ba2+ (100 microM) blocked the inward rectifier K+ current induced by 5-HT. I5
      HT was irreversibly depressed by intracellular application of guanosine 5'-O-(3
      thiotriphosphate)(GTP-gamma S) but not by guanosine 5'-O-(2-thiodiphosphate) (GDP
      beta S). These results suggest that in rat DLSN neurons activation of 5-HT1A
      receptors causes a hyperpolarizing response by activating mainly the inward
      rectifier K+ channels through a GTP-binding protein.

PMID- 9914717
TI  - Validation of the Michigan Alcoholism Screening Test--Thai version in northeast
      Thailand.
AB  - This study was aimed to validate the Michigan Alcoholism Screening Test-Thai
      version (MAST-T) which was compared to the psychiatric diagnosis based on DSM-III
      R criteria, as a gold standard, among the northeast population of Thailand. Sixty
      one pairs of male cases with alcohol use disorders (AUD) and controls were
      collected through routine examination of psychiatric outpatients, 18-65 years
      old, who visited the Khon Kaen Psychiatric Hospital or the Northeast Drug
      Dependence Treatment Center which is located in Khon Kaen province, northeast
      Thailand between November, 1996 and February, 1997. Controls were matched for
      each case by sex-age (+/- 5 years)--province--urbanization. They were interviewed
      using the MAST-T and a structured questionnaire. Receiver operating
      characteristic analysis revealed that the optimum cutoff point > or = 11 on the
      MAST-T yields the best sensitivity and specificity (98.4% for each), along with
      an area under the curve of 0.998, indicating that it was sensitive and specific
      in discriminating AUD from non-AUD patients. This validation study of the MAST
      Thai version underlines its applicability as a screening test for AUD among the
      northeast male Thai population.

PMID- 9914718
TI  - Changes of cerebral hemodynamics and oxygenation in unstable septic newborns
      during exchange transfusion.
AB  - We investigated the effect of a two-way exchange transfusion on cerebral
      hemodynamics and oxygenation in 3 neonates using near infrared spectroscopy
      (NIRS). A total of 4 exchange transfusions (ET) for the treatment of sepsis were
      performed. Cerebral oxyhemoglobin concentrations (HbO2) increased immediately
      after commencing with ET by 8.82 +/- 3.46 (mean +/- SD) micromol/l, which
      persisted throughout the ET. Total hemoglobin concentrations (HbT) simultaneously
      increased by 8.92 +/- 3.81 (mean +/- SD) micromol/l. No changes in cerebral
      deoxyhemoglobin concentrations (HbR) and cytochrome aa3 (Cytaa3) were observed.
      In one occasion, however, HbR increased markedly and HbO2 decreased immediately
      after ET had begun, thus HbT remained slightly increased compared to the 3 other
      occasions. The extension of periventricular echogenecity was observed after ET by
      cranial ultrasound scan in this patient and periventricular leukomalacia was
      confirmed by autopsy. We conclude that a two-way exchange transfusion increases
      cerebral blood volume and improves cerebral oxygen delivery. Furthermore NIRS was
      useful in monitoring changes in cerebral hemodynamics and oxygenation in unstable
      septic neonates.

PMID- 9914719
TI  - Calcitonin gene-related peptide-, neuropeptide Y- and tyrosine hydroxylase
      immunoreactive nerve fibers in the human umbilical cord.
AB  - The distribution of nerve fibers positive for calcitonin gene-related peptide
      (CGRP), which is a vasodilator peptide, neuropeptide Y (NPY), which is a
      vasoconstrictor peptide, and tyrosine hydroxylase (TH), which is a key enzyme for
      the synthesis of the neurotransmitter of adrenergic nerves, was studied in the
      fetal side, middle part, and placental side of the human umbilical cord using
      immunohistochemistry. In the fetal side of the umbilical cord, CGRP-, NPY-, and
      TH-positive fibers were observed in the smooth muscle of the media of the
      umbilical artery and in the margins of the Wharton jelly. They were not observed
      around the umbilical vein or in the middle part or placental side of the
      umbilical cord. These results demonstrate the presence of the vasoactive peptides
      CGRP and NPY, as well as of the enzyme TH in the fetal side of the umbilical
      vessel. The presence of CGRP and NPY suggests the involvement of these peptides
      in the regulation of the umbilical and placental circulation.

PMID- 9914720
TI  - A statistical study of the branching of the human internal iliac artery.
AB  - This study is based on the dissections of 645 pelvic halves of Japanese cadavers.
      The branching of the internal iliac artery was classified according to Adachi's
      classification (1928), and the data was compared with previous reports. Type I
      was predominant in this, as well as, in previous studies. During the course of
      the present study, some branching forms were different from the types in Adachi's
      classification. Therefore, this classification was modified into 5 types and 19
      groups. Type I-Group 1 was most frequently observed in the modified Adachi's
      classification, however, the frequency was less than 50% (46.8%). To clarify the
      basic branching pattern of the original internal iliac artery and to simplify the
      classification for medical purposes, a new classification system was designed.
      The superior gluteal, inferior gluteal and internal pudendal arteries were
      defined as the major branches of the internal iliac artery, and the umbilical
      artery was excluded from this group. The branching of the internal iliac artery
      was classified into 4 groups. Almost 80% of the present specimens were included
      in Group A of the new classification, namely, the internal iliac artery dividing
      into two major branches, the superior gluteal artery and the common trunk of the
      inferior gluteal and internal pudendal arteries. This type of branching seemed to
      be the basic branching pattern for the original internal iliac artery.

PMID- 9914721
TI  - Endoscopic removal with clipping for colonic lipomas.
AB  - Endoscopic removal of colonic lipoma of 2 cm in size or more is not widely used
      because of the risk of complications which are a hemorrhage and a perforation
      associated with endoscopic resection. We report here safety endoscopic removal
      using a bipolar snare and clipping the mucosa of the defective region in three
      cases with large colonic lipoma. We consider that this technique enhanced the
      safety of the endoscopic procedure.

PMID- 9914722
TI  - A patient with Paget's disease of bone treated with etidronate disodium.
AB  - A 69-year-old Japanese woman was referred to our hospital because of abnormal
      skull X-ray findings. Serum total alkaline phosphatase, bone-specific alkaline
      phosphatase 3, osteocalcin and propeptide carboxyterminal of type I procollagen
      (PICP) levels were markedly elevated. Urinary excretion of hydroxyproline was
      also increased, suggesting that both bone formation and resorption were
      accelerated. Radiography of the skull showed "cotton wool" appearance. T1
      enhanced MRI revealed that the skull-cap and diploe were swelled up. In 99mTc-MDP
      bone scintigraphy, all areas of the skull and a part of the right hemipelvis
      showed high uptake of the radioisotope. Based on the findings we made diagnosis
      of Paget's disease of bone which is a rare bone disorder in Japanese. Three-month
      oral administration of etidronate disodium resulted in normalization of serum
      PICP levels and urinary hydroxyproline excretion, whereas alkaline phosphatase
      levels were only partially lowered. Levels of the markers of bone turnover
      remained normal during a follow-up period of 3 months after the discontinuation
      of the treatment.

PMID- 9914723
TI  - Nonfunctioning islet cell carcinoma--a twenty-one years survival case after
      distal pancreatectomy.
AB  - A case of nonfunctioning islet cell carcinoma was reported. A 40-year-old woman
      was admitted with epigastralgia. Abdominal angiography and other diagnostic
      modalities suggested pancreatic malignancy. After distal pancreatectomy,
      histopathological study revealed her pancreatic tumor to be a nonfunctioning
      islet cell carcinoma. Fourteen years later, postoperative computed tomographic
      examination (CT) detected the recurrence of para-aortic lymph node metastases.
      Five years later, distal gastrectomy was performed to control bleeding from a
      gastric ulcer. Twenty-one years after the original operation, she died because of
      underlying metastatic carcinoma. In this case, slow growth and a low grade
      malignancy were characteristic. Operative removal of the tumor would be the
      treatment of choice even if metastatic lesions existed.

PMID- 9914724
TI  - Ventricular septal defect of the atrioventricular canal type--report of a
      surgically treated case.
AB  - A 19-month-old male infant with Down syndrome was referred for investigation of
      heart murmur. An electrocardiogram showed normal axis (+100 degrees) of the QRS
      complex, incomplete right bundle branch block, and biventricular hypertrophy.
      Echocardiography revealed a ventricular septal defect (VSD) and a cleft of the
      anterior mitral leaflet with mild value regurgitation. The anterior mitral
      leaflet and the septal tricuspid leaflet attached to the same level of the
      ventricular septum were also delineated, however, no atrial septal defects were
      detected. Cardiac catheterization demonstrated pulmonary hypertension and a left
      to right shunt at the right ventricle. During operation, no defects in the atrial
      septum and no cleft of the septal tricuspid leaflet were found. Cleft of the
      anterior mitral leaflet, continuity between the mitral anterior leaflet and the
      tricuspid septal leaflet, and a VSD of the atrioventricular canal type were
      confirmed. The cleft of the anterior mitral leaflet and the VSD were repaired
      with the aid of cardiopulmonary bypass. The patient recovered uneventfully.

PMID- 9914725
TI  - [New advances and debated questions in intensive care in the 90-s].
AB  - Author is first dealing with the debate about supranormal oxygen delivery and
      with the Consensus Conference, closing the debate. Author is emphasizing the
      significance of the regional tissue-oxygenisation, which can be measured--in the
      splanchnic region--indirectly by tonometry, suitable for prognostic index too.
      The continuous blood gas analysis became already a fact and for the estimation of
      the cerebral circulation are also developed new methods: the measurement of the
      ajvDO2 and the near infrared spectroscopy. Author outlines the new parameters,
      determining the oxygen-availability (px, Cx, Qx). Finally, author is discussing
      two new american concepts for reducing healthcare costs: flexible monitoring and
      subacute centers.

PMID- 9914726
TI  - [Preventive treatment in internal medicine by low-molecular-weight heparin
      (nadroparine calcium)].
AB  - On the basis of literature data the authors discuss the preventive treatment of
      the low-molecular-weight heparin in various non-surgical disorders. The method
      was compared with unfractionated heparin in the treatment of 20 high risk
      patients. The efficacy of the two different heparins was examined on the liver
      and renal function, blood lipids and the hematologic and hemostaseologic
      parameters. The thromboembolic and hemorrhagic complications were observed.
      Significant difference was not found with the comparison of the two preparations.
      The authors emphasize the simplicity, safety, home treatment possibility of the
      low-molecular-weight heparin and the regular control of thrombocyte-count only,
      too.

PMID- 9914727
TI  - [Effect of somatostatin-octreotide on secretion of adrenocorticotropin, cortisol
      and neuro-hypophyseal hormones in acromegaly].
AB  - The present work was aimed at studying the combined effects of somatostatin and
      corticotropin releasing hormone on the activities of the pituitary-adrenocortical
      axis and neurohypophysis. Patients with active acromegaly were intravenously
      injected with a 100 micrograms human corticotropin releasing hormone bolus before
      and after a 3-month subcutaneous treatment with somatostatin-octreotide (SMS 201
      995; Sandostatin; 200 micrograms t. i. d.). When the Sandostatin effect was
      investigated, corticotropin releasing hormone test was started 2 hrs after its
      first daily dose. Peripheral venous blood samples were taken before and 20, 60,
      90 and 120 min after the corticotropin releasing hormone load. Plasma
      corticotropin, arginine-8-vasopressin and oxytocin were measured by
      radioimmunoassay, and serum cortisol by fluorimetry. In healthy subjects,
      corticotropin releasing hormone stimulus elicited increases of plasma
      corticotropin, serum cortisol, plasma arginine-8-vasopressin and oxytocin levels
      by 186, 41, 178 and 58 per cent, respectively. Untreated acromegalics exhibited
      missing arginine-8-vasopressin, blunted corticotropin, and normal oxytocin and
      cortisol responses. Sandostatin therapy improved the arginine-8-vasopressin
      reaction, suppressed the basal levels of corticotropin and cortisol with the
      maintenance of cortisol stimulability; the peak-reaction of corticotropin became
      normal in two patients, however, with a shortened duration of response. Diuresis
      of the patients increased under the treatment. Sandostatin markedly alleviated
      the clinical symptoms and suppressed the growth hormone secretion, but did not
      influence the size of the pituitary adenomas. Among other factors, the
      alterations of growth hormone and cortisol may be hypothesized to take part in
      the changes of the corticotroph and neurohypophysial functions.

PMID- 9914728
TI  - [Use of studies on genome polymorphism in follow up after allogenic bone marrow
      transplantation].
AB  - The study of structures polymorphic in size found in the human genom (the VNTR
      loci) enables us to differentiate two individuals or--after bone marrow
      transplantation--to detect the simultaneous presence of two genoms in patients'
      blood or marrow. The existence of mixed chimerism may influence the therapy. The
      authors have screened 54 patients, transplanted in their Institute, and their
      donors by determination of four polymorphic loci. Informative marker was found in
      43 cases. The bone marrow transplantation immunotherapy of 29 patients could be
      followed over 2-36 months. To increase the sensitivity of the polymerase chain
      reaction method used, the authors introduced the blotting/hybridization steps
      using isotop labeled repetitive sequences. The results are presented in
      comparison with literature data.

PMID- 9914729
TI  - [Giant cell interstitial pneumonia].
AB  - GIP is a rarely occurring disorder. There is only few literature from its first
      description. Authors observed the course of GIP in the case of a 54 year old
      female patient in the form of bilateral disseminated microfocal pulmonary
      shadows, increased reticular outline with associated respiratory insufficiency.
      Open fine needle pulmonary biopsy proved giant cell desquamative alveolitis with
      help of light- and electronmicroscopical and histochemical examinations. Although
      possibility of exogenic, inhalative factor or/and infectious origin arose in
      causing the disease, disposition from the patient's actual immunological status
      could had helped the evolution of the disease. This fact seemed to be supported
      by the histologically proven associated dermatitis purpurica pigmentosa
      (Schamberg disease). With methylprednisolon therapy full radiological recovery
      occurred, while Schamberg disease was little influenced by the above mentioned
      therapy. The patient is pulmonologically symptom-free and without complaint after
      1 year without any steroid-medication.

PMID- 9914730
TI  - [High-resolution computer tomography of diffuse infiltrative lung diseases].
AB  - During a period of 17 months, a total of 101 patients were examined by high
      resolution computed tomography (HRCT) whose minor focal changes revealed by chest
      X-ray raised the suspicion of diffuse infiltrative pulmonary disease. The disease
      of the interstitium was primarily caused by idiopathic pulmonary fibrosis (19%),
      autoimmune disease (18%), Boeck sarcoidosis (18%) as well as by specific (16%)
      and aspecific inflammation (12%). HRCT disclosed reticular (61%), nodular (55%),
      ground-glass opacity-like (48%), emphysematous (33%) and ring-like changes (17%).
      Also transbronchial excision was performed in 51 patients the results of which
      were compared to the changes observed during HRCT. Concerning fibrosis and
      inflammation, HRCT and histological analysis showed identical results in 70%.
      According to the authors observations, this technique is suitable for detection
      of fairly fine fibrotic, empysematous and inflammatory signs and for defining the
      activity of the individual disease as also for the selection of the optimal site
      of transbronchial excision. HRCT is a useful investigative method both for
      diagnosing diffuse infiltrative pulmonary disease as well as in following up the
      effectiveness of treatment.

PMID- 9914732
TI  - [Multiple endocrine adenomatosis IIB].
AB  - The first Hungarian MEN IIB (multiplex endocrine neoplasia) syndrome is reported
      with the short summary of the literature about the pathogenesis and diagnosis of
      medullary thyroid carcinoma, presenting 80% in sporadic, 20% in hereditary form.
      The appearance of the patients alone (marfanoid stature, bulky lips, and
      ganglioneuromatosis of the tongue) may be almost enough for the presumption for
      the diagnosis of MEN IIB: For screening and preventing the clinical manifestation
      of the very aggressive medullary carcinoma in the relatives of the patient, the
      genetic screening is indispensable. The costs of the genetic screening and early
      treatment of the patients are much lower than the expenses of the traditional
      annual biochemical screening and the--delayed, often only supportive--treatment
      of the clinically manifested illness.

PMID- 9914731
TI  - [Thrombophilia, anticoagulant therapy and pregnancy].
AB  - Thromboembolic complications during pregnancy are the most common causes of
      maternal death. Here we report on thromboembolic prophylaxis of 60 pregnancies of
      32 pregnant women with familial thrombophilia. Long-term Fraxiparine (Sanofi
      Chinoin) as thromboprophylaxis was applied in 26 cases throughout pregnancy. UFH
      (Heparin-Ca inj.) was used in 11 cases, and there were 23 pregnancies without
      thromboembolic prophylaxis in our patient's case histories. Artificial abortions
      were not included in this paper. The ratio of successful pregnancies were: with
      Fraxiparine: 24/26 (92.3%), with UFH (Heparin-Ca): 8/11 (72.7%), without
      prophylaxis: 4/23 (17.4%). In the patient group treated with Fraxiparine there
      were no foetopathy, thrombocytopenia or bleeding complication. LMWH is
      recommended for pregnant women with familial thrombophilia. According to
      literature data and our own experiences the doses of LMWH in patients with
      familial thrombophilia, and -antiphospholipid syndrome, and -artificial heart
      value are suggested.

PMID- 9914733
TI  - [Molecular biologic screening test (PCR) for fragile X syndrome].
AB  - Fragile X syndrome is the most common inherited from of familial mental
      retardation. It is caused by an expanded CGG repeat in the first exon of the
      fragile X mental retardation gene. A polymerase chain reaction based technique
      was used for the identification of full mutations among men. According to our
      conditions full mutations failed to amplify. An internal control was used at a CG
      rich region 147 bp upstream of the polymorphic region. The bands were visualised
      on silver stained polyacrylamide gels. From the 57 individuals studied molecular
      analysis was performed on 38 males and 16 females. From the 26 males with
      suspected fragile X syndrome 9 males resulted in no amplification of the 500 kb
      product, all having a positive cytogenetic result for fragile X syndrome. One
      cytogeneticly positive male had normal results by molecular studies suggesting a
      different mutation. All control males had normal results. The results on the 16
      females studied were inconclusive. We suggest that our method is highly sensitive
      and specific for screening males for fragile X syndrome.

PMID- 9914734
TI  - [Effect of chronic anemia on the endothelium-dependent dilatation of the brachial
      artery].
AB  - The effect of changes in main determinants of whole blood viscosity after red
      blood cell transfusion on endethel dependent dilatation of brachial artery was
      studied in patients treated with transfusion because of symptoms of chronic
      anaemia. PATIENTS AND METHODS: 10 patients were involved, 8 females 2 males, mean
      age 50.9 +/- 16.6 years. Following blood tests were performed at hospital
      admission: hemoglobin, red blood cell count, heamatocrit, white blood cell count,
      platelet count, plasma total protein, fibrinogen, plasma viscosity, blood urea
      nitrogen, creatinine, cholesterol, triglicerides. Flow mediated dilatation of
      brachial artery was determined, too. Blood tests and flow mediated dilatation
      study were repeated after transfusion. RESULTS: The main determinants of whole
      blood viscosity increased after transfusion. The increase of hemoglobin, red
      blood cell count, hematocrit were highly significant. The central flow velocity
      in brachial artery decreased at rest and during hyperemia as well. The flow
      mediated dilatation of brachial artery wasn't significantly changed by
      transfusion. CONCLUSIONS: Change of determinants of whole blood viscosity caused
      by transfusion didn't change the flow mediated dilatation of brachial artery. The
      probable reason for this that the increase of whole blood viscosity in associated
      with the decrease of central flow velocity. These two counteracting changes
      probably equal each other.

PMID- 9914735
TI  - [Geza dabasi-Halasz, M. D., academician, epidemiologist, first Hungarian advocate
      for life insurance].

PMID- 9914736
TI  - [Requiem for a migratory congress. The Migratory Congress series for Hungarian
      Physicians and Naturalists ceased to exist in 1848].

PMID- 9914737
TI  - [What are the costs of the diagnosis and therapy of hepatitis B in a single
      patient in Hungary today?].

PMID- 9914738
TI  - [What is an optimal number of Cesarean sections?].

PMID- 9914739
TI  - [To understand and to explain].

PMID- 9914740
TI  - [The Nobel Prize in physiology or medicine].

PMID- 9914741
TI  - [Drinking-water and health].

PMID- 9914742
TI  - [Piercing].

PMID- 9914743
TI  - [Hundred years of randomized controlled trials].

PMID- 9914744
TI  - [Is drug advertising reliable?].
AB  - In order to assess the quality of pharmaceutical advertising in Norway, we
      conducted a review of advertisements for selective serotonin re-uptake inhibitors
      published in the Journal of the Norwegian Medical Association and the journal
      Legemidler og samfunn during the period 1995-97. 18 advertisements with 38
      reference citations were identified. In six citations (16%), errors made it
      impossible to identify the source with certainty solely on the basis of the
      advertisement. Under Norwegian drug advertisement regulations, a total of 56
      statements should have been followed by a reference citation. In 18 of these
      (33%), it was debatable whether the statements were in accordance with the
      regulations. This review indicates that a significant proportion of the
      statements in drug advertisements is inaccurate and gives a too positive picture
      of the properties of the drug.

PMID- 9914745
TI  - [Curriculum vitae aortae].
AB  - The Greek word aorta means lifter. The vessel was so termed because Aristotle,
      who first described it, assumed that the heart was lifted by/hanging in aorta.
      Leonardo da Vinci described the detailed anatomy of aorta. During the 17th
      century our present understanding of the aorta and the circulation of blood took
      form due to the descriptions given by William Harvey. The first known operation
      for abdominal aortic aneurysm was performed in London in 1817 by Sir Astley
      Cooper who ligated the infrarenal aorta above the aneurysm. Puncture with needles
      and application of electricity were later tried in order to induce thromboses in
      the aneurysm. In 1948 Albert Einstein was operated with wrapping of his abdominal
      aneurysm with cellophane. In 1955 he suffered rupture and died after having
      refused operation. In 1951 the first successful operation for abdominal aortic
      aneurysm was performed in Paris by Charles Dubost. With slight modifications, the
      same operative technique is used today.

PMID- 9914746
TI  - [The first cesarean section in Norway].
AB  - The first reported caesarean section in Norway was performed on 20 August 1843 by
      a general practitioner, Lars Thalian Backer (1812-84). The operation took place
      in Lardal, Vestfold County, on a 27 year old woman who had been in labour for six
      days. The outcome was disastrous; she was delivered of stillborn twins and died 2
      1/2 days after the operation. In the 19th century, infection, bleeding and
      thromboembolic disease made caesarean section a dangerous operation, and only 26
      such operations are known in Norway, most of them performed outside hospitals.
      The first caesarean section in Norway resulting in a living child was performed
      in 1849, but no mother survived the operation before 1890. We recapitulate the
      caesarean section of 1843; Dr Backer and his qualifications for operative
      obstetrics; and the state of instrumental and surgical obstetrics in Norway at
      that time.

PMID- 9914747
TI  - [The introduction of obstetric forceps in Norway--a 250-year anniversary].
AB  - Johan Gottfried Erichsen (1713-68), born in Germany and chief medical officer in
      Bergen from 1747, was probably the first to perform a forceps delivery in Norway,
      on 14 February 1748. The mother, who had been in labour for five days, survived;
      the child, however, did not. The obstetric forceps had been a secret in the
      Chamberlen family and had become more widely known only a few decades earlier.
      Erichsen, who was the first man-midwife in Norway, had learned obstetrics in
      Paris by the younger Gregoire. He mastered both the techniques of internal
      version and forceps delivery. This article describes Erichsen's medical and
      obstetric background and his qualifications for operative obstetrics. He worked
      in the period when the obstetric forceps changed obstetrics, birth delivery
      became an arena also for men, and a part of medicine. Obstetrics was established
      as a science and physicians had a tool whereby also children could be saved
      during complicated delivery.

PMID- 9914748
TI  - ["An appropriate forceps"--150-year anniversary of Simpson's forceps].
AB  - Despite the increasing use of caesarean section and vacuum extraction, obstetric
      forceps is still in frequent use in obstetric wards. There has, in fact, been an
      increase due to more active management of births. More than 600 obstetric forceps
      have been described in detail, but only three of them are in use in Norway today:
      Simpson's and Kielland's forceps for vertex presentation and Piper's forceps for
      aftercoming head in breech presentation. This year it is 150 years since James
      Young Simpson (1811-70) of Edinburgh presented his forceps for the first time.
      Simpson's forceps has been the most widely used forceps in Norway over the last
      120 years. This article describes James Young Simpson, his long forceps, and its
      use in Norwegian obstetrics.

PMID- 9914749
TI  - [History of the reflex hammer].
AB  - The knee jerk was first described by Erb and Westphal in 1875. In subsequent
      years neurologists used direct finger taps and light-weight chest percussion
      hammers, but these proved to be inadequate for eliciting muscle stretch reflexes.
      The first hammer specially designed for eliciting such reflexes was the
      triangular reflex hammer introduced by John Madison Taylor in 1888. Over the next
      25 years several popular reflex hammers were designed, some of which are still in
      use. These include the Babinski hammer with a round head fixed perpendicular to
      the shaft, and Rabiner's modification where the head can also be attached
      parallel to the shaft.

PMID- 9914750
TI  - [Who were the healers in medieval Trondheim?].
AB  - When Trondheim celebrated its millenium in 1997, this also marked a 1000 year-old
      medical tradition. In medieval times, sick and disabled people made their
      pilgrimage to the Nidaros cathedral and the grave of Saint Olav (995-1030).
      Working from the assumption that every organized society develops rituals and
      rules to deal with disease and death, we have looked for evidence of what kind of
      healers one would expect there were in medieval Trondheim up to the reformation
      in 1537. Sources include reports from archaeological excavations, written
      material of both medieval and more recent origin, buildings and objects, and
      living traditions. Three kinds of healer traditions can be identified: The
      popular and "wise" folk healers were based on traditional pre-Christian mythology
      and belief in natural forces. The charitable clerics emerged with Christianity.
      The "professional" wound healers evolved from the needs of the military, later to
      merge with the early barber surgeons. Traces of scientific traditions, the
      Salerno school and early European university medicine can be found in local
      texts, but there is no evidence of any university educated doctor practising in
      Trondheim before the 17th century.

PMID- 9914751
TI  - [The murder at Grunerlokken--a centenary].
AB  - In December 1898, a five year old boy was found murdered and sexually abused at
      Grunerlokka in Oslo. The crime was reported to the police by a 19 year old boy,
      who soon after was detained and charged with the misdeed. In spring 1899 he was
      found guilty and sentenced to life imprisonment with hard labour. This article is
      based on a long and detailed forensic medical and psychiatric report from the
      investigation and trial, published in this Journal in 1899, and on the Oslo press
      coverage of the crime. It shows that much has changed during these 100 years
      regarding both the privacy of the victim, the accused and their families, and
      factors paid attention to in the psychiatric assessment of the accused.

PMID- 9914752
TI  - [The contribution of civilian health and social workers in the districts of Vardo
      and Gamvik during World War II].
AB  - The eastern part of the county of Finnmark in North-Norway played a prominent
      part in the German planning of the attack on Murmansk in 1941. The Norwegian
      civilian population suffered badly from the warfare. In the last phase of the
      war, the Germans burnt down and destroyed almost everything in the entire county,
      and a considerable part of the Norwegian population was forced to evacuate. This
      paper recounts some of the wartime episodes on the coast between the city of
      Vardo and the Nordkinn peninsula. Vardo with its hospital and a number of fishing
      harbours were completely destroyed. Attention is drawn to the excellent job done
      by the civilian Norwegian health and social workers during the terrible years of
      German occupation.

PMID- 9914753
TI  - [The contribution of civilian health and social workers in the districts of Sor
      Varanger and Vadso during World War II].
AB  - Finnmark is the northernmost county in Norway, bordering on Russia. During the
      Second World War, Eastern Finnmark was close to Soviet-German front line. It was
      of vital importance to the Russians to hold on to the ice-free harbour of
      Murmansk. The Norwegian civilian population suffered badly during the war.
      Kirkenes went through 328 bombing raids and furious combat raged in town during
      the German retreat from Finland. The hospitals in Kirkenes and Vadso were
      destroyed. This article gives an account of the wartime experience of civilian
      Norwegian health and social workers in the Kirkenes and Vadso districts and of
      their admirable humanitarian effort.

PMID- 9914754
TI  - [Mining and dentistry].
AB  - Major Norwegian 19th-century mines had their own company physicians. Some of
      their reports and the mine sick-lists have been kept. From the Modum Blue Colour
      Works we have more than 80 such reports or sick-lists (each covering a four-week
      mining period) from 1823 to 1839. Of a total of 8,798 patients, 67 (0.8%) were
      diagnosed as suffering from odontalgia. The treatment was extraction or
      medication. Patients who underwent tooth extraction had fewer subsequent sick
      days than those who were only given medication. Other registrated dental or oral
      disorders included dental abscess, caries, dental cancer with growth on the gums,
      thrush, dentition, dental fever and scorbutus.

PMID- 9914755
TI  - [Alexander Borodin--physician, chemist, scientist, teacher and composer].
AB  - Concert programmes and CD covers suggest that the Russian composer Alexander
      Borodin (1833-87) was also a great scientist. In this article we examine this
      proposition. Borodin was born in St. Petersburg as the illegitimate son of a
      Russian nobleman. As a boy his talents ranged from music to chemistry and
      languages. Borodin studied medicine at the Medico-Surgical Academy in St.
      Petersburg from 1850 to 1855 and defended his doctoral thesis on the similarity
      between arsenic and phosphoric acid in 1858. He did not, however, feel
      comfortable in his role as a doctor, and soon started to work as a chemist. In
      1864 he was appointed professor of chemistry at the Medico-Surgical Academy. In
      1861, Borodin attended the first international congress of chemistry in
      Karlsruhe, and he was among the founders of the Russian Chemical Society in 1868.
      He published 42 articles and was a friend of Dmitri Mendeleev, the scientist who
      described the periodic system. In 1872, Borodin started the first medical courses
      for women in Russia. It seems warranted to conclude that Alexander Borodin was
      indeed a great scientist and university teacher, though his immortality was
      earned by his leisure time activities.

PMID- 9914756
TI  - [Jevgenij Botkin--personal physician of the tzar--an obituary 80 years after his
      death].
AB  - On 17 July 1998 the remains of Tsar Nicholas II and his family were buried, a
      historic event extensively covered by the media. The remains of four servants
      liquidated with the royal family were buried with them. Among the servants was
      the Tsar's personal physician, Jevgenij Botkin. Not often does a doctor follow
      his patients not only onto death, but into death--the Hippocratic oath leading to
      liquidation, so to speak. Who was Dr. Botkin? Did he know what to expect, or was
      he just a chance victim?

PMID- 9914757
TI  - ["The piano trio" Robert Schumann, Clara Schumann and Johannes Brahms].
AB  - The relationship between the pianist and composer Clara Schumann and the
      composers Robert Schumann and Johannes Brahms has for a century been an
      interesting topic. Clara and Robert Schumann both suffered separation from their
      mothers during early childhood. Johannes Brahms was intensely spoiled by his
      mother. Robert Schumann needed a structuring wife in his adult life, while
      Johannes Brahms turned to be afraid of intrusive women. Robert Schumann's
      psychotic breakdown in February 1854 had a complex background: a hypomanic state,
      some marital problems, a stressful journey with musical appearances, and possibly
      a difficulty in differentiating between himself and his new friend Johannes
      Brahms. As for Clara Schumann, who lost her mother before the age of five,
      musical activities became her way of overcoming the difficulties of life. She was
      able to support Robert in his lunatic asylum and their seven children growing up
      in three separate towns. The chronic diseases of the sons: schizophrenia,
      polyarthritis and tuberculosis made a deep impression on her and her fingers and
      hands were periodically immobilised with severe pain. For four decades Johannes
      was her able "son" and Clara was his "mother", at a safe distance.

PMID- 9914758
TI  - ["It is difficult to move a writing pen"--an interpretation of subtext in Agnar
      Mykle's work].
AB  - This article embarks from knowledge gained from dialogues with adult men and
      women in a phenomenological-hermeneutical study of the long-term health impact of
      sexual boundary violations in childhood. All published texts by the Norwegian
      novelist Agnar Mykle have been reviewed for the purpose of a reinterpretation,
      together with scholarly work on his oeuvre and biographical accounts of the
      author and his first wife. The interpretation has been guided by the assumption
      that the essays, novels and letters may represent a double text with an embedded
      coded message. The suggestion is offered that Mykle's work can be read as an
      attempt at acknowledging and surmounting a basic conflict in the author's own
      life between, on the one hand, his memories of experiences of boundary violations
      in childhood and, on the other, a scientific theory of infantile sexuality. It is
      also claimed that Mykle was silenced by the experience of being tried on
      pornography charges against one of his novels. The impact of this public
      humiliation may, in Mykle's perception, have reactivated earlier boundary
      violations and, as such, have been experienced as a revictimisation.

PMID- 9914759
TI  - [Heinrich von Kleist and the true nature of man].
AB  - In short-stories, novels and plays, the artist's interpretation of human nature
      may render the reader valuable insights into the basics of human behaviour. This
      article is a discussion of a short-story about a fictitious earthquake in Chile,
      written in 1807 by Heinrich von Kleist (1777-1811). The writer shows how feelings
      of warmth, friendliness and solidarity come out when a catastrophe reduces the
      relative importance of man-made rules and regulations. But more sombre sides of
      human nature also come to the surface in the wake of the disaster, and the writer
      indicates that even the apparently virtuous Christian morality contains severe
      traits of cruelty and repressiveness.

PMID- 9914760
TI  - [An enemy of the people--Ibsen as a teacher of public health].
AB  - This article is a study of the play An Enemy of the People (1882) by Henrik Ibsen
      (1828-1906). One of its main characters, Dr Tomas Stockmann, has a crucial role
      in the discussion about the medical conditions at the public baths. Four excerpts
      from the play is presented for further discussion. The focus of this article is
      on Dr Stockmann's work as a public health physician: What causes Dr Stockmann's
      failure in bringing his report on the medical conditions at the baths to the
      public? What can physicians in general learn from Dr Stockmann? The article
      concludes that Dr Stockmann richly illustrates communicative failure and that he
      is a complex figure, provocative as well as inspiring--something in between a
      medical savage and a public health hero.

PMID- 9914761
TI  - [Cover motifs of the Tidsskrift. A 14-year cavalcade].
AB  - In 1985 the Journal of the Norwegian Medical Association changed its cover
      policy, moving the table of contents inside the Journal and introducing cover
      illustrations. This article provides an analysis of all cover illustrations
      published over this 14-year period, 420 covers in all. There is a great variation
      in cover motifs and designs and a development towards more general motifs. The
      initial emphasis on historical and medical aspects is now less pronounced, while
      the use of works of art and nature motifs has increased, and the cover now more
      often has a direct bearing on the specific contents of the issue. Professor of
      medical history Oivind Larsen has photographed two thirds of the covers and
      contributed 95% of the inside essay-style reflections on the cover motif. Over
      the years, he has expanded the role of the historian of medicine disseminating
      knowledge to include that of the raconteur with a personal tone of voice. The
      Journal's covers are now one of its most characteristic features, emblematic of
      the Journal's ambition of standing for quality and timelessness vis-a-vis the
      news media, and of its aim of bridging the gap between medicine and the
      humanities.

PMID- 9914762
TI  - [Organization and substrate of memory].
AB  - Recently, we have witnessed considerable progress in the field of memory
      research. New approaches and techniques have allowed the fractionation of memory
      in several subentities. Working memory, in which sensory information is
      manipulated for 10-20 seconds, is served by an area laterally in the frontal
      lobes. Long-lasting memories are either of the explicit or implicit variety.
      Contents of explicit memory stores can be accessed by conscious processes and
      depend upon medial temporal lobe structures, in particular the hippocampal
      formation. Implicit memories can not be consciously accessed and have its many
      substrates distributed to different parts of the brain, depending upon the
      material or procedures involved. Long-term memories are reconstructive and thus
      amenable to forgetting, alteration and, in some cases, even repression.

PMID- 9914763
TI  - [Visual hallucinations in ophthalmological and neurological diseases].
AB  - Visual hallucination can be defined as visual sensory perception without external
      stimulation, or something that a patient sees that other observers in the same
      environment do not see. The images may be unformed (lights, streaks, flashes) or
      formed (objects, people, scenes). Clinical experience indicates that, despite the
      infrequency with which they are mentioned, visual hallucinations commonly occur
      in patients with ophthalmological and neurological diseases. Content, duration
      and timing of visual hallucinations relate to their cause and provide useful
      clinical information. This paper reviews the topical, pathophysiological and
      clinical aspects of visual hallucinations.

PMID- 9914764
TI  - [Waiting lists as results of statistic coincidences].
AB  - Queues and waiting lists in the health services are central issues in the
      political debate in Norway. By means of a simulation programme (Powersim), we
      demonstrate some elementary properties of queuing. We show that stochastic entry
      to the service and stochastic need for service can produce queues. We also show
      that a queue-free service will need an unrealistically high and abundant
      capacity.

PMID- 9914766
TI  - [Hunting for "womanhood"].

PMID- 9914765
TI  - [Psychoanalysis beyond Freud].
AB  - Since Sigmund Freud (1856-1939) formulated his first psychoanalytic theories
      about 100 years ago, there has been a rapid development in psychoanalytic theory
      and therapy. In this paper, central concepts in the four psychoanalytic
      "psychologies"--drive/ego psychology, object relations theory, self psychology
      and interpersonal psychoanalysis--are presented. Basic concepts in psychoanalysis
      have been under a continuous critical review, and psychoanalytic theories remain
      versatile. The unconscious and the exploration of subjective experience are
      central common themes. The role of the psychoanalyst has changed from expert to
      explorer, working together with the patient. At the same time, the analyst has
      become more active in the therapy room. The analyst's contribution to what is
      happening between the analyst and the patient has been increasingly emphasized.
      The development in psychoanalysis has parallelled both developments in the theory
      of knowledge as well as the change in cultural trends. Creating meaning is
      central to the psychoanalytic process, but there are divergent views as to how
      this happens: by articulating meaning, by uncovering meaning, by constructing or
      deconstructing meaning. The narrative tradition in which the central point is to
      tell stories about oneself, is discussed more thoroughly in the paper. The
      authors challenge the view that psychoanalysis is the work of Freud only.

PMID- 9914767
TI  - [The oldest "medicine". Wine and health--from Nippur to the Osterbro study].

PMID- 9914768
TI  - [But God was not dead?].

PMID- 9914769
TI  - [Physician's role].

PMID- 9914770
TI  - [Kaspase or caspase?].

PMID- 9914771
TI  - [The system of family practitioners should be rejected].

PMID- 9914772
TI  - [Solo practice and family practitioners?].

PMID- 9914773
TI  - Current estimates from the National Health Interview Survey, 1995.
AB  - OBJECTIVES: This report presents data on national estimates of the incidence of
      acute conditions, percent of medically attended acute conditions, number of
      disability days (including restricted activity and bed days, and work- or school
      loss days), number of episodes of persons injured and associated activity
      restriction, prevalence of selected chronic conditions, number of activity
      limitations due to chronic conditions, number of restricted activity days
      associated with acute and chronic conditions, respondent-assessed health, number
      of physician contacts, and short-stay hospitalizations. METHODS: The National
      Health Interview Survey (NHIS) is a complex, multi-stage, probability sample
      survey conducted annually by trained interviewers of the U.S. Bureau of the
      Census for the National Center for Health Statistics. Information is collected
      during in-home interviews of the civilian noninstitutionalized U.S. population on
      a variety of health issues. RESULTS: The NHIS estimates that in 1995, there were
      174.4 acute conditions per 100 persons. Of these, 67.3 percent were medically
      attended and this resulted in 674.6 days of restricted activity per 100 persons.
      Of acute injuries, 91.2 percent were medically attended. The most frequently
      reported rates for chronic conditions per 1,000 persons included sinusitis
      (141.3), arthritis (124.7), and deformity and orthopedic impairment (121.4). Some
      degree of activity limitation due to chronic conditions was reported by 14
      percent of persons. There were about six physician contacts per person per year
      and 7.5 percent of the population had at least one hospitalization in the past
      year.

PMID- 9914774
TI  - Society for Maternal-Fetal Medicine 19th annual meeting. San Francisco,
      California, USA. January 18-23, 1999. Abstracts.

PMID- 9914775
TI  - c-kit gain-of-function mutations and human tumors.

PMID- 9914776
TI  - Expression of telomerase catalytic component, telomerase reverse transcriptase,
      in human gastric carcinomas.
AB  - Telomerase activity is believed to be crucial for cellular immortality, which is
      considered to participate in the development of a majority of human cancers.
      Human telomerase reverse transcriptase (TERT) has recently been identified as a
      catalytic subunit of telomerase. We examined the expression of TERT and other
      telomerase components such as human telomerase RNA component (hTR, encoded by
      TERC) and human telomerase-associated protein (TEP1) by reverse transcription
      polymerase chain reaction in human gastric carcinomas and non-neoplastic mucosa,
      in addition to measuring the telomerase activity. Of 20 gastric carcinomas
      examined, 18 (90%) and 18 (90%) showed increased expression of TERT and higher
      telomerase activity in comparison with corresponding non-neoplastic mucosa,
      respectively. Increased expression of hTR/TERC was also observed in 15 (75%) of
      the gastric carcinomas. Immunohistochemically, strong expression of TERT protein
      was detected in the nuclei of the tumor cells of all carcinoma tissues, while the
      expression of TERT in non-neoplastic mucosal cells as well as stromal elements
      (except lymphocytes) was weak or negative. These findings suggest that increased
      TERT expression associated with telomerase activity may serve as a novel marker
      for the diagnosis of stomach cancer.

PMID- 9914777
TI  - Generation of metastatic variants of Eker renal carcinoma cell lines for
      experimental investigation of renal cancer metastasis.
AB  - We and others have demonstrated that a mutation in Tsc2 is the rate-limiting step
      for renal carcinogenesis in the Eker rat model. Although inactivation of Tsc2
      results in development of renal tumors, it is not sufficient for metastatic renal
      cell carcinomas (RCs) in the Eker rat. To investigate the additional genetic
      event(s) necessary for cancer metastasis, we have established highly metastatic S
      Lk9d-SLM cell lines from a non-metastatic RC cell line (Lk9dL) by co-implantation
      with a foreign body (gelatin sponge). Since these cell lines were remarkably
      different in metastatic performance (all and none, respectively) despite having
      the same genetic background, they should be useful experimental tools to
      investigate metastasis-promoting events in renal carcinogenesis.

PMID- 9914778
TI  - Helicobacter pylori risk associated with sibship size and family history of
      gastric diseases in Japanese adults.
AB  - Helicobacter pylori is thought to be a cause of gastric cancer. Risk factors of
      H. pylori positivity were investigated among 4,361 public service workers in
      Japan. Sera and information on family history and lifestyle were collected, and
      H. pylori antibody was measured using the sera. Sex- and age-adjusted odds ratios
      of factors expected to influence H. pylori seropositivity were calculated. The
      factors with a significant influence were included in a logistic regression model
      and the final model was obtained by backward elimination. Sibship size (4 and
      more vs. 1), smoking habit (current vs. never), and paternal and siblings'
      histories of gastric diseases showed significant relationships to H. pylori
      seropositivity, with odds ratios (95% confidence intervals) of 1.5 (1.0-2.1), 0.8
      (0.7-0.9), 1.5 (1.3-1.8) and 1.7 (1.1-2.6) respectively. However, spouse's
      history was not related. In the final model, sibship size and paternal history
      remained as positive factors, and smoking as a negative one. Contradictory
      results on the relationship between H. pylori status and smoking among recent
      studies indicate the existence of hidden confounding factors. It is suggested
      that infection from family members in childhood considerably affects the H.
      pylori status of Japanese adults, whereas infection between adults is rare.

PMID- 9914779
TI  - Modulation of dihydroxy-di-n-propylnitrosamine-induced liver lesion development
      in Opisthorchis-infected Syrian hamsters by praziquantel treatment in association
      with butylated hydroxyanisole or dehydroepiandrosterone administration.
AB  - The effects of praziquantel coupled with dehydroepiandrosterone (DHEA) or
      butylated hydroxyanisole (BHA) administration 16 weeks subsequent to dihydroxy-di
      n-propylnitrosamine (DHPN) treatment and infection with Opisthorchis viverrini
      (OV) on lesion development in the liver of Syrian hamsters were investigated.
      Animals were given 80 OV metacercariae and then two i.p. injections of DHPN (500
      mg/kg body weight) 4 and 5 weeks thereafter. At week 16, groups received
      praziquantel (250 mg/kg, i.g.) and were placed on normal diet or diet
      supplemented with BHA (1%) or DHEA (0.6%) until they were killed at week 24.
      Histopathological assessment revealed that, whereas antihelminthic treatment
      alone resulted in a clear reduction in hepatocellular lesion development, effects
      on cholangiocellular lesions were equivocal. BHA and DHEA, in contrast, were both
      associated with a significant reduction in frequency of cholangiofibrosis and
      cholangiocellular carcinoma. The former chemical, however, increased the numbers
      of liver nodules while the hormone brought about a decrease as well as a shift in
      the phenotype of the lesions. The results thus indicate that although
      cholangiocellular lesion development may, unlike generation of hepatocellular
      nodules, be to a certain extent independent of the continued presence of
      parasite, it can be influenced by exogenous treatments.

PMID- 9914780
TI  - Inhibition of early-phase exogenous and endogenous liver carcinogenesis in
      transgenic rats harboring a rat glutathione S-transferase placental form gene.
AB  - Hepatocarcinogenesis initiated with N-nitrosodiethylamine (DEN) and that
      initiated by feeding of a choline-deficient, L-amino acid-defined (CDAA) diet
      were compared in transgenic male Wistar rats harboring a rat glutathione S
      transferase placental form (GST-P) gene (GST-P-Tg rats) and non-transgenic (N-Tg)
      rats. Eight-week-old GST-P-Tg and N-Tg rats were administered DEN
      intraperitoneally at 100 mg/kg body weight, subjected to a selection procedure
      with 2-acetylaminofluorene and CCl4, and killed at the end of weeks 5 and 12.
      Other groups were fed the CDAA diet for 12 weeks and killed. Five weeks after the
      DEN treatment, numbers and sizes of gamma-glutamyltransferase (GGT)- or GST-P
      positive lesions and 8-hydroxyguanine (8-OHG) levels in the livers were
      significantly less in GST-P-Tg rats than in N-Tg rats. The lesion numbers were
      unchanged between the ends of weeks 5 and 12 in GST-P-Tg rats, but decreased in N
      Tg rats. The lesion sizes were increased in GST-P-Tg rats, but unchanged in N-Tg
      rats. While the proliferating cell nuclear antigen labeling indices (PCNA L.I.)
      in and surrounding the lesions were decreased, more prominently in GST-P-Tg rats
      than in N-Tg rats, the 8-OHG levels were also decreased but similarly in both
      cases. After 12 weeks on the CDAA diet, the lesion incidences, numbers and sizes,
      8-OHG levels, PCNA L.I. in and surrounding the lesions, and liver injury were
      significantly less in GST-P-Tg rats than in N-Tg rats. These results indicate
      that insertion of a rat GST-P transgene alters the early phase of exogenous and
      endogenous rat hepatocarcinogenesis, presumably due to enhanced detoxification by
      GST-P expressed both transiently during the initiation and chronically in the
      altered hepatocyte populations.

PMID- 9914781
TI  - Phorbol ester-induced G1 arrest in BALB/MK-2 mouse keratinocytes is mediated by
      delta and eta isoforms of protein kinase C.
AB  - We investigated the possible negative regulation of the cell cycle by protein
      kinase C (PKC) isoforms in synchronously grown BALB/MK-2 mouse keratinocytes, in
      which PKC isoforms were overexpressed by using the adenovirus vector Ax. Cells at
      the G1/S boundary of the cell cycle were the most sensitive to the inhibitory
      effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC agonist, resulting in
      G1 arrest. TPA-induced inhibition of DNA synthesis was augmented by
      overexpression of the eta and delta isoforms, but rescued by the dominant
      negative and antisense eta isoforms. In contrast, the alpha and zeta isoforms
      showed no effect on DNA synthesis with or without TPA treatment. Immunoblotting
      indicated cell cycle-dependent expression of the eta isoform, being highest in
      cells at the G1/S boundary. The present study provides evidence that the eta and
      delta isoforms of PKC are involved in negative regulation of cell cycle at the
      G1/S boundary in mouse keratinocytes.

PMID- 9914782
TI  - Mammary fibroblast-derived hepatocyte growth factor stimulates growth and
      morphogenesis of mouse mammary tumor cells in primary culture.
AB  - We have recently isolated a mammary growth factor from the conditioned medium of
      mouse mammary stromal fibroblasts and identified it as a mouse homologue of human
      HGF (hepatocyte growth factor). To elucidate the role of HGF in mouse mammary
      tumorigenesis, we produced recombinant mouse HGF and examined its effects on
      primary cultures of mouse mammary tumor cells in this study. HGF at
      concentrations above 20 ng/ml maximally stimulated the growth of mammary tumor
      cells in primary monolayer culture. HGF also stimulated the three-dimensional
      growth and branching morphogenesis of mammary tumor cells cultured inside
      collagen gels. A comparison of the growth-stimulating activity of HGF with that
      of EGF (epidermal growth factor) and KGF (keratinocyte growth factor) revealed
      that HGF is the most potent growth factor among the three. Immunological studies
      using an antibody against mouse HGF demonstrated that 74% of the growth
      stimulating activity present in the mammary fibroblast-conditioned medium was
      abolished by the antibody, indicating that HGF is the major growth factor
      produced by the fibroblasts. These observations thus suggest a role for HGF as a
      mammary stromal fibroblast-derived factor which stimulates growth and
      morphogenesis of adjacent mammary tumor cells in vivo.

PMID- 9914783
TI  - Relationship between protein levels and gene expression of dihydropyrimidine
      dehydrogenase in human tumor cells during growth in culture and in nude mice.
AB  - Protein levels and gene expression of dihydropyrimidine dehydrogenase (DPD), the
      rate-limiting enzyme for degradation of 5-fluorouracil, were studied in two human
      tumor cell lines (fibrosarcoma HT-1080 and pancreatic carcinoma MIAPaCa-2) in
      various growth phases of the cultured cells and of tumor xenografts implanted
      into nude mice. DPD catalytic activity and DPD protein content in cytosolic
      preparations were determined by means of radioenzymatic assay and western blot
      analysis, respectively. Relative DPD mRNA expression was determined by using a
      semi-quantitative reverse transcription-polymerase chain reaction in which
      glyceraldehyde-3-phosphate dehydrogenase mRNA was used as an internal standard.
      DPD activity and protein content in cultures of both cell lines increased in
      proportion to cell density (DPD activities ranged from undetectable to 84
      pmol/min/mg protein in the HT-1080 cells and from undetectable to 335 pmol/min/mg
      protein in the MIAPaCa-2 cells). DPD mRNA levels, on the other hand, tended to
      decrease slightly during cell growth. DPD activity and protein content in HT-1080
      tumor xenografts increased during growth in proportion to tumor weight (DPD
      activities ranged from 7 to 131 pmol/min/mg protein), but DPD mRNA levels did not
      correlate with tumor weight. DPD activity and protein content in MIAPaCa-2 tumor
      xenografts did not change much, and seemed to have already plateaued, since the
      tumors were small (weighing about 30 mg). These findings suggest that DPD protein
      expression during tumor growth is controlled at the post-transcriptional level.

PMID- 9914784
TI  - Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymerase
      beta.
AB  - Lithocholic acid (LCA), one of the major components in secondary bile acids,
      promotes carcinogenesis in rat colon epithelial cells induced by N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG), which methylates DNA. Base-excision repair of
      DNA lesions caused by the DNA methylating agents requires DNA polymerase beta
      (pol beta). In the present study, we examined 17 kinds of bile acids with respect
      to inhibition of mammalian DNA polymerases in vitro. Among them, only LCA and its
      derivatives inhibited DNA polymerases, while other bile acids were not
      inhibitory. Among eukaryotic DNA polymerases alpha, beta, delta, epsilon, and
      gamma, pol beta was the most sensitive to inhibition by LCA. The inhibition mode
      of pol beta was non-competitive with respect to the DNA template-primer and was
      competitive with the substrate, dTTP, with the Ki value of 10 microM. Chemical
      structures at the C-7 and C-12 positions in the sterol skeleton are important for
      the inhibitory activity of LCA. This inhibition could contribute to the tumor
      promoting activity of LCA.

PMID- 9914785
TI  - CD44H participates in the intrahepatic growth of murine colon 26 adenocarcinoma
      cells.
AB  - The purpose of this study was to determine if CD44, a metastasis-associated cell
      adhesion molecule, is involved in the hepatic colonization by murine colon 26
      adenocarcinoma cells. Indirect membrane immunofluorescence and FACS analysis
      showed strong expressions of CD44 and integrin beta 1 on colon 26 cells.
      Injection of 1 x 10(5) colon 26 cells into the superior mesenteric vein of
      syngeneic BALB/c mice produced macroscopic hepatic nodules in 92% (22/24) of the
      mice 14 days after inoculation. When colon 26 cells were pretreated with an anti
      CD44 monoclonal antibody (mAb), IM7, only 30% (3/10) of the mice produced minute
      nodules in the liver on day 14 (P < 0.001), though IM7 did not inhibit growth of
      the cells in vitro. Pretreatment of colon 26 cells with an anti-integrin beta 1
      mAb did not significantly block the hepatic metastasis. Histologically,
      microcolonies of tumor cells were detected in all of the livers on day 14
      including the IM7-pretreatment mice that were free of gross nodules. However,
      percentages of tumor-occupied areas in the liver were consistently lower in IM7
      pretreatment mice than in control mice (0.82% vs. 5.0% on day 14; P < 0.005).
      Reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA
      revealed that colon 26 cells and splenocytes only expressed the hematopoietic
      isoform of CD44 (CD44H), which had no insertion of variant exons, while normal
      colonocytes expressed possible variant isoforms. These data suggest that
      malignant transformation of murine colonic epithelium altered the expression
      pattern of CD44 isoforms and that CD44H participates in the intrahepatic growth
      of colon 26 cells.

PMID- 9914786
TI  - A novel mutant from apoptosis-resistant colon cancer HT-29 cells showing hyper
      apoptotic response to hypoxia, low glucose and cisplatin.
AB  - Solid tumors usually have regions of hypoxia and glucose deprivation. Human colon
      carcinoma HT-29 cells show an apoptosis-resistant phenotype in response to
      microenvironmental stresses. In this study, we isolated a novel mutant of HT-29,
      designated as HA511, that showed a high apoptotic response to hypoxia, glucose
      deprivation and treatment with the chemical stressors tunicamycin and
      glucosamine. The mutant HA511 cells exhibited nuclear condensation and
      fragmentation and activation of CPP32 (caspase-3) protease under the stress
      conditions, while the parental HT-29 cells did not. We found that apoptosis
      occurred in HA511 cells after prolonged cell cycle arrest at the G1 phase, while
      in the parental cells a progression to S phase occurred after the G1 arrest. Upon
      exposure to an anti-Fas antibody, HA511 cells underwent apoptosis, whereas the
      parental cells proliferated without substantial cell death. Furthermore, HA511
      cells were preferentially hypersensitive to cisplatin. We found no alteration in
      expression of GRP78, anti-apoptotic protein Bcl-XL, or p53, of which the gene was
      mutated in HT-29 cells. The mutant HA511 cells could provide useful information
      on the mechanism of apoptosis of solid tumors.

PMID- 9914787
TI  - Characterization of a human small-cell lung cancer cell line resistant to a new
      water-soluble camptothecin derivative, DX-8951f.
AB  - DX-8951f, a water-soluble and non-pro-drug analogue of camptothecin, exhibits a
      strong inhibitory action on DNA topoisomerase I (Topo I) and in vitro
      cytotoxicity against various human cancer cell lines. In order to elucidate the
      mechanisms of its cytotoxicity, we established a DX-8951f-resistant cell line,
      SBC-3/DXCL1, from human small cell lung cancer cells (SBC-3) by stepwise exposure
      to DX-8951f. SBC-3/DXCL1 cells were approximately 400 times more resistant to DX
      8951f than parent cells. The SBC-3/DXCL1 cells showed a high degree of cross
      resistance to other Topo I inhibitors such as CPT-11, SN-38 and camptothecin, but
      not to non-Topo I targeting agents such as cisplatin, adriamycin, etoposide, and
      vincristine. The mechanisms of resistance of SBC-3/DXCL1 cells to DX-8951f were
      examined. Intracellular accumulation of DX-8951f by SBC-3 and SBC-3/DXCL1 cells
      did not differ significantly. Although the Topo I activity of nuclear extracts
      obtained from SBC-3/DXCL1 cells was the same as that of the parent cells, the
      Topo I of SBC-3/DXCL1 cells was resistant to the inhibitory effects of DX8951f
      and SN-38. Immunoblotting using anti-Topo I antibody demonstrated similar protein
      levels of Topo I in SBC-3 and SBC-3/DXCL1 cells. The active Topo I protein of SBC
      3/DXCL1 was eluted by a high concentration of NaCl (0.4 N) compared with that of
      SBC-3 (0.3 N). DX-8951f stabilized the DNA-Topo I cleavable complex from SBC-3
      cells, as measured by Topo I-mediated cleavage assay. In SBC-3/DXCL1 cells, DX
      8951f also stabilized the DNA-Topo I complex, but with a 10-fold lower
      efficiency. These results suggest that a qualitative change in Topo I
      contributes, at least partially, to the resistance to DX-8951f in SBC-3/DXCL1
      cells. Therefore, SBC-3/DXCL1 cells may have a unique mechanism of resistance to
      Topo I-directed antitumor drugs.

PMID- 9914789
TI  - High rate of induction of human autologous cytotoxic T lymphocytes against renal
      carcinoma cells cultured with an interleukin cocktail.
AB  - A high rate of induction (9 of 10 cases) of human autologous cytotoxic T
      lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells
      of renal carcinoma patients by applying an interleukin (IL)-cocktail consisting
      of IL-1, -2, -4, and -6. The CTL specifically lysed their own target carcinoma
      cells within 24 h but did not kill neighboring autologous normal kidney cells or
      allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous
      CTL were not induced, no expression of MHC class-I molecules was observed on the
      surface of these carcinoma cells, although they were sensitive to autologous
      natural killer cells. The results imply that adoptive immunotherapy for
      metastasized renal carcinoma will be feasible with autologous CTL in combination
      with natural killer cells.

PMID- 9914788
TI  - In situ mRNA hybridization technique for analysis of human telomerase RNA in
      gastric precancerous and cancerous lesions.
AB  - Telomerase, the ribonucleoprotein enzyme that elongates telomerase, is repressed
      in normal somatic cells but is reactivated during tumor progression. The purpose
      of this study was to investigate the localization of human telomerase RNA (hTR)
      expression in human gastric precancerous and cancerous lesions by using in situ
      mRNA hybridization (ISH) with avidin-biotin staining. We also examined telomerase
      activity in these lesions by using hybridization protection assay connected with
      a telomeric repeat amplification protocol (TRAP/HPA). Analyzed tissue samples
      were as follows; 132 cases of chronic atrophic gastritis without intestinal
      metaplasia, 115 incomplete-type intestinal metaplasias, 40 complete-type
      intestinal metaplasias, 23 hyperplastic polyps, 23 tubular adenomas and 26
      adenocarcinomas. In ISH analysis, high levels of hTR expression were observed
      preferentially in the nuclei at the single-cell level. hTR-expressing cells in
      carcinomas and adenomas were significantly more frequent than those of the other
      lesions (P < 0.001). The expression pattern of hTR in carcinoma and adenoma
      tissues was heterogeneous and similar intratumor heterogeneity was detected in Ki
      67 immunoreactivity. Infiltrating lymphocytes in tissue also exhibited high
      levels of hTR expression. In TRAP/HPA analysis, carcinomas had significantly more
      frequent positivity for telomerase activity and a higher level of telomerase
      activity than the other lesions (P < 0.05). However, the amount of telomerase
      activity did not parallel the expression level of hTR. Our data suggest that hTR
      expression increases in the early stages of stomach carcinogenesis and that
      sufficient synthesis of hTR is a prerequisite for telomerase reactivation in
      tumorigenesis.

PMID- 9914790
TI  - Antitumor effect of diphtheria toxin A-chain gene-containing cationic liposomes
      conjugated with monoclonal antibody directed to tumor-associated antigen of
      bovine leukemia cells.
AB  - Monoclonal antibody c143 against tumor-associated antigen (TAA) expressed on
      bovine leukemia cells was conjugated to cationic liposomes carrying a plasmid
      pLTR-DT which contained a gene for diphtheria toxin A-chain (DT-A) under the
      control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) in the
      multicloning site of pUC-18. The specificity and antitumor effects of the
      conjugates were examined in vitro and in vivo using TAA-positive bovine B-cell
      lymphoma line as the target tumor. In vitro studies with the TAA-positive cell
      line indicated that luciferase gene-containing cationic liposomes associated with
      the c143 anti-TAA monoclonal antibody caused about 2-fold increase in luciferase
      activity compared with cationic liposomes having no antibody, and also that the
      c143-conjugated cationic liposomes containing pLTR-DT exerted selective growth
      inhibitory effects on the TAA-positive B-cell line. Three injections of pLTR-DT
      containing cationic liposomes coupled with c143 into tumor-bearing nude mice
      resulted in significant inhibition of the tumor growth. The antitumor potency of
      the c143-conjugated cationic liposomes containing pLTR-DT was far greater than
      that of normal mouse IgG-coupled cationic liposomes containing pLTR-DT as
      assessed in terms of tumor size. These results suggest that cationic liposomes
      bearing c143 are an efficient transfection reagent for BLV-infected B-cells
      lymphoma cells, and that the delivery of the pLTR-DT gene into BLV-infected B
      cells by the use of such liposomes may become a useful technique for gene therapy
      of bovine leukosis.

PMID- 9914791
TI  - Targeted gene transfer for adenocarcinoma using a combination of tumor-specific
      antibody and tissue-specific promoter.
AB  - We have developed a highly specific gene transfer method for adenocarcinoma using
      a monoclonal antibody against tumor-specific antigen coupled with a plasmid
      containing the carcinoembryonic antigen (CEA)-specific promoter. The chimeric CEA
      promoter (CC promoter), which contained an enhancer from the immediate early gene
      of cytomegalovirus and the CEA promoter, achieved 4- to 5-fold higher transgene
      expression in CEA-producing cells than the original CEA promoter while
      maintaining CEA specificity. Furthermore, a complex of a monoclonal antibody
      against Lewis Y antigen (LYA), the CC promoter-containing plasmid and cationic
      liposomes (DOTAP) achieved specific gene expression in CEA-producing and LYA
      positive adenocarcinoma cell lines that was 200-fold more efficient than in CEA
      non-producing and LYA-negative cell lines during a short in vitro incubation.
      This strategy may be applicable for clinical gene therapy.

PMID- 9914792
TI  - Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of
      doxorubicin and vinblastine via human P-glycoprotein.
AB  - The inhibitory effects of SDZ PSC 833 (PSC833), a non-immunosuppressive
      cyclosporin derivative, on the P-glycoprotein (P-gp)-mediated transport of
      doxorubicin and vinblastine were compared with those of cyclosporin A (Cs-A). The
      transcellular transport of the anticancer drugs and PSC833 across a monolayer of
      LLC-GA5-COL150 cells, which overexpress human P-gp, was measured. Both PSC833 and
      Cs-A inhibited P-gp-mediated transport of doxorubicin and vinblastine in a
      concentration-dependent manner and increased the intracellular accumulation of
      doxorubicin and vinblastine in LLC-GA5-COL150 cells. The values of the 50%
      inhibitory concentration (IC50) of PSC833 and Cs-A for doxorubicin transport were
      0.29 and 3.66 microM, respectively, and those for vinblastine transport were 1.06
      and 5.10 microM, respectively. The IC50 of PSC833 for doxorubicin transport was
      about 4-fold less than that for vinblastine transport, suggesting that the
      combination of PSC833 and doxorubicin might be effective. PSC833 itself was not
      transported by P-gp and had higher lipophilicity than Cs-A. These results
      indicated that the inhibitory effect of PSC833 on P-gp-mediated transport was 5-
      to 10-fold more potent than that of Cs-A, and this higher inhibitory effect of
      PSC833 may be related to the absence of PSC833 transport by P-gp and to the
      higher lipophilicity of PSC833.

PMID- 9914794
TI  - Student evaluations of dental faculty and courses.

PMID- 9914795
TI  - "And the band played on...".

PMID- 9914793
TI  - A new antitumor agent amrubicin induces cell growth inhibition by stabilizing
      topoisomerase II-DNA complex.
AB  - Amrubicin is a novel, completely synthetic 9-aminoanthracycline derivative.
      Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human
      DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and
      amrubicinol induced extensive DNA-protein complex formation and double-strand DNA
      breaks in CCRF-CEM cells and KU-2 cells. In this study, we found that ICRF-193, a
      topo II catalytic inhibitor, antagonized both DNA-protein complex formation and
      double-strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell
      growth inhibition induced by amrubicin and amrubicinol, but not that induced by
      DXR, was antagonized by ICRF-193. Taken together, these findings indicate that
      the cell growth-inhibitory effects of amrubicin and amrubicinol are due to DNA
      protein complex formation followed by double-strand DNA breaks, which are
      mediated by topo II.

PMID- 9914796
TI  - A distance learning program in advanced general dentistry.

PMID- 9914797
TI  - A history of otology through the development of scientific and medical thought.
AB  - The story of the development of civilisation and of humanity is at the base of
      science, medicine and otology in particular. The evolution of knowledge is better
      understood by dividing the story into chronological periods. Through primitive,
      archaic, hellenistic, byzantine, arabian, monastic, scholastic, Renaissance,
      modern and finally contemporary medicine, otology has progressively found its
      way. The key to progress is within man, in his conception of life and of the
      world around him. Otology will be affected by these different trends of thought
      and will find its place in medicine during the XIX Century, the XX Century being
      its most prolific period.

PMID- 9914798
TI  - Cochlea: forms and philosophy.
AB  - The relationship between the general form of the cochlea and its function is
      difficult to study. The logarithmic nature of the spiroid can be deduced from
      embryologic data and the development of the cochlea around a nervous system. The
      propagation of sound has been studied through linear models. Experiments in fluid
      mechanics show that the parameters of viscosity and surface tension can modify
      the surface pattern. These data could permit the conception of 3D-models to
      explain cochlear cybernetics uniting maximal efficiency with a minimal volume.

PMID- 9914799
TI  - Role of speech therapy and sign language prior to cochlear implantation.
AB  - The speech therapist should assess and develop the communication skills of the
      deaf child prior and after a cochlear implantation. The goals are first the
      acquisition of a useful communication system by the deaf child (for avoiding a
      cognitive stimulation lack) and parallely the acquisition of good oral language
      competencies. The different modes of communication useable in the profoundly deaf
      education are presented. Exclusive sign language use is not indicated in
      implanted children. It is well demonstrated that an exclusive oral communication
      is associated with an insufficient knowledge of the oral language. The total
      communication (combination of listening, speech reading, signing with or without
      finger spelling) is a defective communication mode with a bad representation of
      the morpho-syntactic and the phonologic aspects of the oral language. The best
      choice seems to be the simultaneously use of a spoken language and a manually
      coding of their phonological structures. The limits of this alternative are
      discussed.

PMID- 9914800
TI  - Benign paroxysmal positional vertigo. State of the art.
AB  - This paper defines the benign paroxysmal vertigo (BPV). It recalls the
      ethiopathogeny of the syndrome and describes the different types of BPV and their
      treatment by "liberatory maneuvers". The paper also discusses the need for an
      otoneurological examination to achieve an exact diagnosis.

PMID- 9914802
TI  - Tracheotomy in neonates.
AB  - The particularities and complications of tracheotomy in neonates, as well as
      postoperative care and follow-up are presented. During the five year period from
      1991-1996, 12 urgent tracheotomies were performed on 12 neonates in the
      Hippokration Hospital of Thessaloniki, 7 boys and 5 girls, ranging from 1 to 25
      days. All these infants presented severe respiratory failure due to upper airway
      obstruction. Endotracheal intubation was attempted on all of them with no
      success, and urgent tracheotomy was recommended by the neonatologists. Three out
      of the twelve neonates died (the first during the procedure, the second just
      after the procedure and the third one week later) while the remaining nine were
      relieved from respiratory distress. Tracheotomy is a procedure of major
      importance for the survival and further development of young patients.

PMID- 9914801
TI  - Benign positioning vertigo (BPV) and three-dimensional (3-D) eye movement
      analysis.
AB  - Fifty two patients with positioning nystagmus were studied with the V.N.G. three
      dimentional device of ULMER. In benign paroxysmal positional vertigo (BPPV) the
      torsionnal component is not pure: a vertical and a less important horizontal
      components also exist. They are not of the same amplitude on both eyes. The
      torsionnal and horizontal components are more important on the eye ipsilateral to
      the BPPV. The vertical component is more important on the contralateral eye. The
      horizontal canal B.P.V. (2% of the cases of B.P.V.) is so defined by the absence
      of vertical and torsionnal components. Three-D Eye Movement Analysis is helpful
      for differential diagnosis with the positional protocol described. The
      characteristics of central and peripheral paroxysmal positional nystagmus are
      given. The head Tilt and the ocular counter rolling reflex (O.C.R.) can be
      quantified with this device. It will be useful in the future to better explore
      the inferior root of the eighth nerve and the otolith organ. For clarity we
      propose to describe the torsionnal nystagmus so that the results are expressed
      with respect to the patient: clockwise nystagmus (in reference to the patient)
      would thus be also right rotatory nystagmus while left rotatory nystagmus would
      be also anticlockwise.

PMID- 9914803
TI  - Validation of hearing results in tympanoplasty: a preliminary report.
AB  - In the otological literature, the results of middle ear surgery are frequently
      reported by closure of the air-bone gap and improvement of the air-conduction
      threshold in dB HL. These parameters are valid as a reflection of the technical
      success, but do not evaluate the effect of surgery on binaural hearing. In the
      literature two methods have been proposed for predicting patient benefit in
      reconstructive middle ear surgery: the Rule of Thumb and the Glasgow Benefit
      Plot. Both methods are based on the arbitrary cut-off level of 30 dB HL for
      normal or socially acceptable hearing. However, a reliable preoperative
      prediction of patient benefit can only be made after validation of the definition
      of normal or socially acceptable hearing expressed in dB HL by means of a
      questionnaire measuring the limitations of adequate hearing. A clear relationship
      is found between the subjective hearing ability and the air-conduction thresholds
      that supports 30 dB HL as the cut-off level for normal or socially acceptable
      hearing. Further validation of this cut-off level in a more extensive prospective
      study is needed to provide a significant prognosis for normal or socially
      acceptable hearing.

PMID- 9914804
TI  - Total auricular repair: bone anchored prosthesis or plastic reconstruction?
AB  - Major breakthroughs in implantology and prosthetic materials, but also in
      reconstructive surgery of the auricle, have opened new possibilities in the
      rehabilitation of patients with an absent auricle. The management of such cases
      and the surgical results in 62 cases are presented. Thirty-five bone-anchored
      prostheses have been adapted and 27 total auricular reconstructions performed. As
      long as the conditions of osseo-integration are respected, surgery for an
      epithesis is easy and comprises no major risks. The side effects of the
      percutaneous connection (mainly skin reactions) are often minor. All patients are
      satisfied with their prosthesis and wear it all day long. For the total auricular
      repair, mainly in major congenital malformations, two techniques were adopted:
      first the Brent technique followed by the Nagata technique, preferred nowadays.
      The Brent technique was found safe with good results, but the modification by
      NAGATA offered two additional advantages: a reduction of the operative stages
      from 4 to 2 and a better definition of the auricular reliefs by the more
      elaborate fabrication of the framework. With increasing experience the results of
      the total auricular reconstructions improved significantly and became more
      predictable. Also the advantages and disadvantages of both (the reconstructive
      and prosthetic) approaches are discussed.

PMID- 9914805
TI  - Cervico-thoracic goiter. A case report.
AB  - The definition, mode of development and symptomatology of cervico-thoracic
      goiters are described. The treatment of choice is a total thyroidectomy. The
      indication of each step in the preoperative work-up and the details of the
      surgical technique specific for cervico-thoracic goiters are reviewed. The choice
      between a purely cervical and a cervico-thoracic approach remains controversial
      in function of the morbidity.

PMID- 9914806
TI  - Endoscopic septal spur resection in combination with endoscopic sinus surgery.
AB  - To assess the possibilities and limitations of endoscopic septal spur resection
      in combination with endoscopic sinus surgery, 40 consecutive patients were
      prospectively evaluated. All patients suffered from chronic sinusitis and
      presented with a posterior septal spur. The spur resection was mainly done
      because of impaction on the middle meatus and was in general performed after the
      sinus procedure, if technically possible. Although not completely painless, the
      septal spur resection could be easily performed under local anesthesia. The
      procedure took on average less than 5 minutes. The immediate postoperative period
      was always uneventful and no septal perforations were recorded at six weeks.
      There were no late complications. In conclusion, endoscopic resection of a septal
      spur can be performed safely in combination with endoscopic sinus surgery and
      contributes with minimal additional morbidity to the surgical success.

PMID- 9914807
TI  - [The pulmonary surfactant system: physiology, pathologies associated with its
      alteration and exogenous administration as therapeutic and diagnostic agent].
AB  - Pulmonary surfactant is a lipoproteic mixture synthesized and secreted by
      alveolar type II cells. Its principal property is to reduce the surface tension
      by lining on the alveolar surface. Surfactant deficiency is the major factor
      responsible for the respiratory distress syndrome of the newborn (RDS) and the
      adult respiratory distress syndrome (ARDS). Since 1980, the exogenous
      administration of surfactant for the treatment of these syndromes is being
      studied. In this work the exogenous surfactant preparations, the delivery
      techniques and the dosing schedule is discussed. The utilization of the exogenous
      natural surfactant (ENS) as precursor of a radiopharmaceutical labeled with 99mTc
      (99mTc-ENS) for aerial lung scintigraphy is also discussed.

PMID- 9914808
TI  - Fluoxetine action upon human T lymphocyte proliferation.
AB  - The purpose of this study was to analyze the effect of fluoxetine upon human T
      lymphocyte proliferation, and to assess the early signals elicited after T cell
      triggering and cAMP formation. Blood samples from normal human volunteers were
      drawn from venipuncture and T cells were cultured in the presence or absence of
      Concanavalin A (Con A) and fluoxetine. Protein Kinase C (PKC) levels and cyclic
      adenosine monophosphate (cAMP) formation were also measured. Fluoxetine exerted
      dual effect, depending on the degree of lymphocyte activation: at mitogenic
      concentrations of Con A (2 micrograms/ml), we observed an inhibitory effect on
      cellular proliferation. This inhibitory effect involves PKC degradation and cAMP
      formation. On the other hand, when submitogenic Con A concentrations (1
      microgram/ml) were used, fluoxetine stimulated the cellular response and
      increased PKC translocation. The participation of extracellular calcium
      mobilization could be involved in these mechanisms. According to our results,
      fluoxetine seems to modulate calcium influx which, in turn, would influence PKC
      translocation, thus modulating the immune response through a mechanism that could
      be involving cAMP participation.

PMID- 9914809
TI  - The anthelmintic albendazole affects in vivo the dynamics and the detyrosination
      tyrosination cycle of rat brain microtubules.
AB  - Albendazole (ABZ) is an anthelmintic benzimidazole drug widely used in human and
      veterinary medicine. ABZ has binding affinity to both mammalian and helminth
      parasite tubulin. In the current work, we have performed in vitro assays and in
      vivo experiments in which rats were given ABZ orally to better characterize the
      action of the drug on the polymerization of rat brain microtubules and on the
      detyrosination/tyrosination cycle that occurs on the COOH-terminal end of alpha
      tubulin. The results showed that ABZ inhibits brain microtubule polymerization in
      vitro, and significantly delayed microtubule assembly in vivo. The tyrosination
      reaction cycle was not affected in vitro; however, in rats to which the drug was
      administered orally, the levels of in vitro tyrosination were reduced when
      compared to the controls with mock treatment. These results suggest that this
      apparent inhibition would be due to a decrease in the amount of substrate caused
      by the depolymerizing effect of ABZ and the subsequent tyrosination in the intact
      brain with endogenous tyrosine. In conclusion, ABZ strongly affects tubulin
      dynamics both in vivo and in vitro. The outcome of these experiments is a
      contribution to the understanding of the molecular mechanisms involved in the
      antimicrotubular action of benzimidazole compounds.

PMID- 9914810
TI  - Urinary elimination of erythropoietin in patients under treatment with
      cytostatics drugs.
AB  - Reductions in the hemoglobin (Hb) mass are followed by increases in the level of
      plasma erythropoietin (EPO) concentrations which are directly proportional to the
      level of the hormone required to bring the hemoglobin values back to normalcy.
      Hypoplastic anemias (AHC) on the other hand, are accompanied by significantly
      larger increases in the erythropoietin concentration. In this study we have
      measured the relationship between the severity of the anemia and the levels of
      erythropoietin elimination in the urine patients (EpoU) under treatment with
      cytostatic drugs. Simultaneously other parameters used as indicators of bone
      marrow activity were determined. These observations suggest that the levels of
      erythropoietin depends not only by the tissue oxygen availability but by others
      factors related to the marrow cellularity.

PMID- 9914811
TI  - [Histological and histochemical study of hyperplastic and dysplastic lesions of
      the large intestine in Cebus Apella (primate) treated with 1,2
      dimethylhydrazine].
AB  - The main objective of this study was to assess the histological changes of colon
      ephitelium in Cebus apella induced by 1,2-dimethylhydrazine (DMH) administration.
      Twelve monkeys, males, (aged x: 30 months) with an average body weight of 2,800 g
      were utilized. The DMH was injected subcutaneously at 25 mg/kg and continued once
      a week for 16 weeks. The body weight was assessed once a week during the first 4
      months and every 30 days until the end of the experience. Histological changes of
      intestinal ephitelium and mucins were assessed at the end of the experience in
      specimens sectioned at 5 microns, stained with Haematoxylin and Eosin, PAS and
      Alcian blue pH 2.5. The histological and histochemical study permitted to
      characterize the normal morphology, as well as the mucins characteristics in the
      three regions: caecum, transverse colon and distal colon. The histological
      changes in the DMH treated animals were hyperplasia, dysplasia and mucins
      decreasing. The hyperplastic changes were localizated in glandular crypts, and in
      the epithelio located over the lymphoid nodules. The dysplastic crypts were
      observed in the transverse colon and in the last portion of distal colon. These
      lesions were located in the upper portion as well as the bottom of the mucosa. A
      decrease of neutral and acids mucopolysaccharides were observed in the crypts.
      The results of this study suggest that the DMH induced hyperplastic changes in
      the crypts and in the epithelium located over the lymphoid nodules and dysplastic
      focus, as well as a decrease of neutral and acids mucopolysaccharides.

PMID- 9914812
TI  - Umbilical cord clamping. An analysis of a usual neonatological conduct.
AB  - Here we described a critical analysis of the neonatological procedure of early
      cord clamping, meaning this, within 40 seconds after birth. Fifty three cases are
      here analysed, in which this practice was not performed, but instead a late
      umbilical cord clamping was done after birth or after the cord had stopped
      beating. Variations in hematocrito values within 24 to 36 hours after birth were
      studied. A transitory polycithemia, with a maximum peak 12 hours post-delivery
      was observed. These values returned to normal levels between 24 and 36 hours
      after birth. K vitamin was not administered to any of the newborns. No pathology
      appeared related to this transitory polycithemia. In can be concluded that the
      late umbilical cord clamping represents no risk to the new-born and that the
      pathological phenomena described under these circumstances may be attributed to
      the increase in K vitamin dependent coagulation factors that are induced by the
      routinary administration of phitonadione to all normal newborns.

PMID- 9914813
TI  - Early lipid alterations in spontaneously diabetic rats.
AB  - Human and experimental diabetes mellitus extensively alters lipid metabolism. The
      eSS is a rat strain that develops a spontaneous diabetes of slow evolution,
      resembling the non-insulin-dependent diabetes mellitus of young people. We report
      here disturbances in lipid metabolism of 5-month old eSS rats compared to age
      matched alpha-controls. Normal plasmatic glucose levels were found in the fasted
      state, whereas a diabetic curve was evident for eSS rats after glucose load.
      Triglyceride content was elevated in plasma and in liver microsomal preparations
      of eSS animals, when compared to the controls. The diabetic strain revealed a
      significant fall in the amount of linoleic acid in liver and kidney microsomes
      and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted.
      A depression in the content of linoleic acid as well as an enhancement of
      docosahexaenoic acid were detected in phosphatidylcholine and
      phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty
      acid pattern of eSS rat testis showed a raise in the relative percentage of
      arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids
      compared to their controls. Diabetic rats exhibited a significant increase in
      microsomal cholesterol content and cholesterol/phospholipid ratio in liver and
      testis. In the latter tissue, higher values of fluorescence anisotropy were also
      observed. The current observations indicate that in early stages of the diabetes
      onset, when eSS rats are still normoglycemic, severe alterations of lipid
      metabolism may contribute to the establishment and progression of the diabetic
      syndrome.

PMID- 9914814
TI  - Designs of reference families for the construction of genetic linkage maps.
AB  - The reference family panel is the foundation of a gene mapping program because it
      affects the cost and quality of the genetic linkage maps, and should be designed
      to yield reliable linkage detection and locus ordering at minimal gene mapping
      cost. A map cost function was defined as the number of genotypes required per
      marker per unit of genome coverage and was used to obtain optimal designs with
      respect to linkage detection. An ordering reliability function was defined as the
      likelihood ratio of the most likely order to the second most likely order of
      genetic markers and was used to find optimal designs with respect to locus
      ordering. Optimum levels of recombination frequency were found to be in the
      neighborhood of 0.11-0.15 for linkage detection and were in the region of 0.05
      0.20 for locus ordering. Therefore, recombination frequencies optimal for linkage
      detection are also optimal for locus ordering. Based on the optimal detection
      levels, sample size (number of offspring) and map cost requirements were derived
      for six representative designs, assuming gender-specific linkage maps and two
      alleles with equal frequency for each marker. The sample size required for
      linkage detection ranged from 168 to 432 offspring for full-sib designs and
      ranged from 350 to 600 offspring for half-sib designs depending on the family
      size and the target LOD score, with corresponding minimal map costs of 10-20
      genotypes per marker per centiMorgan map coverage. Locus ordering generally
      requires more genotypes than linkage detection. For full-sib designs, meioses
      from both genders should be used for locus ordering even when the maps are gender
      specific. For half-sib designs, additional families may be needed for locus
      ordering. Sample size for ordering closely linked loci as required by positional
      cloning were provided. Effects of family size, grandparents, and marker
      polymorphism on design efficiency were analyzed.

PMID- 9914815
TI  - Wanderings in bioenergetics with Licio Azzone.

PMID- 9914816
TI  - Search for novel redox groups in mitochondrial NADH:ubiquinone oxidoreductase
      (complex I) by diode array UV/VIS spectroscopy.
AB  - The proton-translocating NADH:ubiquinone oxidoreductase of mitochondria (complex
      I) is a large L-shaped multisubunit complex. The peripheral matrix arm contains
      one FMN and a number of iron-sulfur (FeS) clusters and is involved in NADH
      oxidation and electron transfer to the membrane intrinsic arm. There, following a
      yet unknown mechanism, the redox-driven proton translocation and the ubiquinone
      reduction take place. Redox groups that would be able to link electron transfer
      with proton translocation have not been found so far in the membrane arm. We
      searched for such groups in complex I isolated from Neurospora crassa. Under
      anaerobic conditions, the preparation was analyzed in different redox states by
      means of UV/VIS and EPR spectroscopy. Absorption bands in the UV/VIS redox
      difference spectra were found which cannot be attributed to the FMN or the EPR
      detectable FeS clusters. The existence of two novel groups is postulated and
      their possible locations in the electron pathway and their roles in proton
      translocation are discussed.

PMID- 9914817
TI  - Three-dimensional structure and functions of bovine heart mitochondrial
      cytochrome bc1 complex.

PMID- 9914818
TI  - Kinetic control of internal electron transfer in cytochrome c oxidase.
AB  - Two alternative hypotheses have been proposed to account for the relatively slow
      (ms) internal eT observed in the oxidized cyt c oxidase. The thermodynamic
      control hypothesis states that eT between cyt a and a3 is very fast
      (microsecond), but the apparent reduction of cyt a3 is slow because
      thermodynamics favors reduced cyt a. Whereas the kinetic control hypothesis
      states that inter-heme eT is intrinsically slow (ms), for the oxidized binuclear
      center. Monitoring by stopped flow the anaerobic reduction of the oxidized enzyme
      by ruthenium hexamine in the absence and presence of CO or NO, used as "trapping"
      ligands for cyt a3(2+), we found that the rate of formation of the cyt a3(2+)-NO
      adduct (k' approximately 20-25 s-1) is independent of the concentration of
      ruthenium hexamine and NO. We conclude that in the oxidized enzyme the two hemes
      are not in very rapid redox equilibrium and internal eT is kinetically
      controlled.

PMID- 9914819
TI  - Oxidative stress, antioxidant defences and aging.
AB  - Apoptosis and aging share common mechanisms in oxidative stress and mitochondrial
      involvement. Treatment of cultured neuroblastoma cells with a radical initiator
      induced apoptosis; raise in hydrogen peroxide and release of cytochrome c from
      mitochondria preceded collapse of mitochondrial potential and cell death. In rat
      hepatocytes treated with adriamycin incubation with exogenous Coenzyme Q10
      counteracted the drug-induced increase of hydrogen peroxide and the fall of the
      mitochondrial potential, thus demonstrating the quinone antioxidant effect.
      Complex I activity and its rotenone sensitivity decreased in brain cortex non
      synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found
      only in the old rats. A similar behavior was found in human platelets from old
      individuals. The postulated energy decline was confirmed by the inhibitor
      sensitivities of platelet aggregation and lactate production. The lack of the 5
      kb deletion in platelets throws doubts on mitochondrial DNA lesions as the only
      causes of mitochondrial dysfunction in aging.

PMID- 9914820
TI  - The interaction of mitochondria with pulses of calcium.

PMID- 9914821
TI  - The structure and function of the brown fat uncoupling protein UCP1: current
      status.
AB  - The uncoupling protein of brown adipose tissue (UCP1) is a transporter that
      allows the dissipation as heat of the proton gradient generated by the
      respiratory chain. The discovery of new UCPs in other mammalian tissues and even
      in plants suggests that the proton permeability of the mitochondrial inner
      membrane can be regulated and its control is exerted by specialised proteins. The
      UCP1 is regulated both at the gene and the mitochondrial level to ensure a high
      thermogenic capacity to the tissue. The members of the mitochondrial transporter
      family, which includes the UCPs, present two behaviours with carrier and channel
      transport modes. It has been proposed that this property reflects a functional
      organization in two domains: a channel and a gating domain. Mounting evidence
      suggest that the matrix loops contribute to the formation of the gating domain
      and thus they are determinants to the control of transport activity.

PMID- 9914822
TI  - Protein translocation into mitochondria.
AB  - The mitochondrial membranes contain translocation machineries ("preprotein
      translocases") which facilitate transport of proteins from the cytosol into the
      mitochondria. The TOM complex is localized in the outer membrane. Two
      translocases have been characterized in the inner membrane: the Tim23-Tim17
      complex and the Tim22 complex which differ in their specificities for
      preproteins. The TOM and TIM complexes can act in a coordinated fashion to
      facilitate the insertion of preproteins into the mitochondrial membranes as well
      as the translocation into the internal compartments, the intermembrane space and
      the matrix. We discuss insights into the function of components of the
      translocases, illustrated by examples for mechanisms of protein sorting into the
      different compartment of mitochondria.

PMID- 9914823
TI  - Electron microscopic tomography of rat-liver mitochondria and their interaction
      with the endoplasmic reticulum.
AB  - Electron microscopic tomography can provide a complete three-dimensional range of
      information about subcellular structures. Applied to mitochondria, it has shown
      that the conventional textbook model of this organelle is incorrect. The
      infoldings of the inner membrane (called cristae) are connected by narrow tubular
      regions to each other and to the outside, suggesting that internal diffusion of
      ions, metabolites and proteins may be restricted. Tomographic reconstruction of
      mitochondria in situ indicates these organelles may occur in clusters with stacks
      of endoplasmic reticulum, forming extended structures that may be involved in
      [Ca++] regulation.

PMID- 9914824
TI  - Some new aspects of creatine kinase (CK): compartmentation, structure, function
      and regulation for cellular and mitochondrial bioenergetics and physiology.
AB  - Creatine kinase (CK) isoenzymes, specifically located at places of energy demand
      and energy production, are linked by a phosphocreatine/creatine (PCr/Cr) circuit,
      found in cells with intermittently high energy demands. Cytosolic CKs, in close
      conjunction with Ca(2+)-pumps, play a crucial role for the energetics of Ca(2+)
      homeostasis. Mitochondrial Mi-CK, a cuboidal-shaped octamer with a central
      channel, binds and crosslinks mitochondrial membranes and forms a functionally
      coupled microcompartment with porin and adenine nucleotide translocase for
      vectorial export of PCr into the cytosol. The CK system is regulated by AMP
      activated protein kinase via PCr/Cr and ATP/AMP ratios. Mi-CK stabilizes and
      cross-links cristae- or inner/outer membranes to form parallel membrane stacks
      and, if overexpressed due to creatine depletion or cellular energy stress, forms
      those crystalline intramitochondrial inclusions seen in some mitochondrial
      cytopathy patients. Mi-CK is a prime target for free radical damage by
      peroxynitrite. Mi-CK octamers, together with CK substrates have a marked
      stabilizing and protective effect against mitochondrial permeability transition
      pore opening, thus providing a rationale for creatine supplementation of patients
      with neuromuscular and neurodegenerative diseases.

PMID- 9914825
TI  - The molecular structure of mitochondrial contact sites. Their role in regulation
      of energy metabolism and permeability transition.
AB  - Contact sites between the outer and peripheral inner membrane of mitochondria are
      involved in protein precursor uptake and energy transfer. Hexokinase and
      mitochondrial creatine kinase could be attributed by different techniques to the
      energy transfer contacts. Kinetic analyses suggested a functional interaction
      between the kinases, outer membrane pore protein, and inner membrane adenylate
      translocator (ANT). This suggestion was strongly supported by isolation of
      hexokinase and creatine kinase complexes that were constituted of kinase
      oligomers, porin and ANT. Phospholipid vesicles carrying reconstituted kinase
      porin-ANT complexes enclosed internal ATP in contrast to vesicles containing free
      porin only. This indicated that unspecific transport through porin was regulated
      by its interaction with a specific antiporter, ANT. A direct interaction between
      porin and ANT in the hexokinase complex conferred the reconstituted system with
      permeability properties reminiscent of the mitochondrial permeability transition
      (PT) pore. In the creatine kinase complex this interaction between porin and ANT
      was replaced by contact of both with the kinase octamer. Thus PT-pore-like
      functions were not observed unless the creatine kinase octamer was dissociated,
      suggesting that the ANT was locked in the antiporter state by interaction with
      the octamer. Indeed, reconstituted pure ANT showed PT-pore-like properties
      concerning Ca2+ sensitivity. However, as cyclophilin was missing, sensitivity
      against cyclosporin was not observed.

PMID- 9914826
TI  - New light on mitochondrial calcium.
AB  - The possibility of specifically addressing recombinant probes to mitochondria is
      a novel, powerful way to study these organelles within living cells. We first
      showed that the Ca(2+)-sensitive photoprotein aequorin, modified by the addition
      of a mitochondrial targeting sequence, allows to monitor specifically the Ca2+
      concentration in the mitochondrial matrix ([Ca2+]m) of living cells. With this
      tool, we could show that, upon physiological stimulation, mitochondria undergo a
      major rise in [Ca2+]m, well in the range of the Ca2+ sensitivity of the matrix
      dehydrogenases, in a wide variety of cell types, ranging from non excitable,
      e.g., HeLa and CHO, and excitable, e.g., cell lines to primary cultures of
      various embryological origin, such as myocytes and neurons. This phenomenon,
      while providing an obvious mechanism for tuning mitochondrial activity to cell
      needs, appeared at first in striking contrast with the low affinity of
      mitochondrial Ca2+ uptake mechanisms. Based on indirect evidence, we proposed
      that the mitochondria might be close to the source of the Ca2+ signal and thus
      exposed to microdomains of high [Ca2+], hence allowing the rapid accumulation of
      Ca2+ into the organelle. In order to verify this intriguing possibility, we
      followed two approaches. In the first, we constructed a novel aequorin chimera,
      targeted to the mitochondrial intermembrane space (MIMS), i.e., the region sensed
      by the low-affinity Ca2+ uptake systems of the inner mitochondrial membrane. With
      this probe, we observed that, upon agonist stimulation, a portion of the MIMS is
      exposed to saturating Ca2+ concentrations, thus confirming the occurrence of
      microdomains of high [Ca2+] next to mitochondria. In the second approach, we
      directly investigated the spatial relationship of the mitochondria and the ER,
      the source of agonist-releasable Ca2+ in non-excitable cells. For this purpose,
      we constructed GFP-based probes of organelle structure; namely, by targeting to
      these organelles GFP mutants with different spectral properties, we could label
      them simultaneously in living cells. By using an imaging system endowed with high
      speed and sensitivity, which allows to obtain high-resolution 3D images, we could
      demonstrate that close contacts (< 80 nm) occur in vivo between mitochondria and
      the ER.

PMID- 9914827
TI  - Role of mitochondria in metabolism-secretion coupling of insulin release in the
      pancreatic beta-cell.
AB  - The control of insulin secretion from the pancreatic beta-cell involves a complex
      cascade of events in which the mitochondria play a central role. In the consensus
      model this role is essentially restricted to the production of ATP promoting
      membrane depolarisation and a rise in cytosolic [Ca2+]. Evidence for the
      generation of an additional mitochondrial factor implicated in metabolism
      secretion coupling is provided in this review. Although not yet identified, the
      formation of this putative factor requires an increase of [Ca2+] in the
      mitochondrial matrix together with a supply of carbons to the tricarboxylic acid
      (TCA) cycle. In this model, calcium activates matrix dehydrogenases, in
      particular those of the TCA cycle. This enables the synthesis of the
      mitochondrial factor from the TCA cycle intermediates. Experimental evidence
      gathered in permeabilised cells largely supports this model.

PMID- 9914828
TI  - Imaging the mitochondrial permeability transition pore in intact cells.
AB  - The involvement of mitochondrial permeability transition pore (MTP) in cellular
      processes is generally investigated by indirect means, such as changes in
      mitochondrial membrane potential or pharmacological inhibition. However, such
      effects could not be related univocally to MTP. In addition, source of errors
      could be represented by the increased retention of membrane potential probes
      induced by cyclosporin A (CsA) and the interactions between fluorescent probes.
      We developed a direct technique for monitoring MTP. Cells were co-loaded with
      calcein-AM and CoCl2, resulting in the quenching of the cytosolic signal without
      affecting the mitochondrial fluorescence. MTP inducers caused a rapid decrease in
      mitochondrial calcein fluorescence which, however, was not completely prevented
      by CsA. Besides the large and rapid efflux of calcein induced by MTP agonists, we
      also observed a constant and spontaneous decrease of mitochondrial calcein which
      was completely prevented by CsA. Thus, MTP likely fluctuates between open and
      closed states in intact cells.

PMID- 9914829
TI  - The mitochondrial permeability transition.
AB  - This review summarizes recent work on the regulation of the permeability
      transition pore, a cyclosporin A-sensitive mitochondrial channel that may play a
      role in intracellular calcium homeostasis and in a variety of forms of cell
      death. The basic bioenergetics aspects of pore modulation are discussed, with
      some emphasis on the links between oxidative stress and pore dysregulation as a
      potential cause of mitochondrial dysfunction that may be relevant to cell injury.

PMID- 9914831
TI  - Neuronal excitotoxicity: the role of mitochondria.
AB  - Chronic activation of NMDA receptors by glutamate is toxic to cultured neurons.
      The extensive Ca2+ entry accompanying receptor activation is largely accumulated
      by the intracellular mitochondria, with resultant effects on mitochondrial
      membrane potential, ATP synthesis, glycolysis, reactive oxygen species generation
      and ultimately failure of cytoplasmic Ca2+ homeostasis and cell death. Each of
      these parameters is inter-related and in this review we describe attempts to
      separate out each factor to establish the sequence of events following NMDA
      receptor activation. The conclusion is that mitochondrial Ca2+ accumulation is a
      key event in glutamate excitotoxicity, and that cells maintained by glycolysis in
      the absence of a mitochondrial membrane potential are highly resistant to
      glutamate excitotoxicity.

PMID- 9914830
TI  - Confocal microscopy of the mitochondrial permeability transition in necrotic cell
      killing, apoptosis and autophagy.
AB  - Onset of the cyclosporin-A-sensitive mitochondrial permeability transition (MPT)
      in individual mitochondria within living cells can be visualized by laser
      scanning confocal microscopy. The MPT is a causative event in many types of
      necrotic and apoptotic cell death, including oxidative stress,
      ischemia/reperfusion injury, Ca2+ ionophore toxicity and tumor necrosis factor
      alpha (TNF alpha) induced apoptosis, and may contribute to Reye's-related drug
      toxicity. Pyridine nucleotide oxidation, mitochondrial generation of reactive
      oxygen species, and increased mitochondrial Ca2+ and pH can each promote onset of
      the MPT in situ. The MPT can also be directly visualized during TNF alpha-induced
      apoptosis to hepatocytes. Mitochondria spontaneously depolarize in situ after
      nutrient deprivation before entering an acidic lysosomal compartment, suggesting
      that the MPT precedes the normal process of mitochondrial autophagy. We propose a
      model in which onset of the MPT to increasing numbers of mitochondria leads
      progressively to autophagy, apoptosis and necrotic cell death.

PMID- 9914832
TI  - ATP as a death factor.

PMID- 9914833
TI  - From bioenergetics to philosophy of science: a brief report of an exciting
      cultural journey.

PMID- 9914834
TI  - [Biophysics and history].
AB  - The results of Chijevsky's study of correlation between solar activity maxima and
      social disturbances are confirmed now using modern technology and large
      historical data. There are some other evidences of the reality this relation. The
      main conclusion is that the creation of new philosophy of history is necessary
      taking into account natural data's sciences.

PMID- 9914835
TI  - [Magnetosensitivity of the epiphysis].
AB  - Literature data and the results of own studies on the sensitivity of the
      epiphysis to variable magnetic fields are reviewed.

PMID- 9914836
TI  - [Optimization of energy-dependent processes in mitochondria from rat liver and
      brain after inhalation of negative air ions].
AB  - The effect of negative air ions (NAI) inhalation by rats on energy reactions of
      mitochondria in homogenates of liver and brain was studied. The influence of NAI
      was investigated under activation of animals by administration of physiological
      dose of adrenaline. Adrenaline administration induced hyperactivation of the rate
      of phosphorylating oxidation of succinic acid in liver and brain mitochondria
      which was accompanied by oxalacetate inhibition of succinate dehydrogenase (SDH)
      as well as excessive Ca2+ accumulation in liver mitochondria. These changes
      connected with a decrease of coefficient of phosphorylation efficiency ADP/O and
      uncoupler stimulation of respiration evidenced decrease of energy control of
      respiration in mitochondria. NAI inhalation diminished the rate of hyperactivated
      respiration and abolished excessive Ca2+ accumulation. These changes together
      with ADP/O coefficient and DNP stimulation increase evidence improvement of
      energy control of respiration which provide more moderate function of the
      respiratory chain under activation by adrenaline. Animals were excited by
      adrenaline administration. This effect was abolished by NAI inhalation, animals
      relaxed, some fell asleep. The data evidence sensitivity of mitochondrial
      processes in internal organs to inhalation of NAI and show participation of
      mitochondria in realization of physiological effects of NAI.

PMID- 9914837
TI  - [Combined effect of weak permanent and variable magnetic fields, adjusted to the
      cyclotron resonance of amino acid ions, on development of Ehrlich ascites
      carcinoma in mice].
AB  - It was shown that weak magnetic fields adjusted to the cyclotron frequencies of
      amino acid ions exert a substantial oncotoxic effect on the developed tumor
      ascites in mice with Ehrlich ascites carcinoma.

PMID- 9914838
TI  - [Phenomenological explanation of reasons for changes in blood flocculation
      reactions].
AB  - The phenomenological interpretation of characteristics of the blood reaction
      flocculation is proposed. Variations of the blood reaction flocculation are
      comparable to transformations of magnetosphere-ionosphere current systems. Short-
      and longtime changes of reaction flocculation parameters are correlates with
      ionospheric current modifications and ionospheric composition.

PMID- 9914839
TI  - [Effect of a weak variable super-low frequency magnetic field on the infradian
      rhythms of physiological systems, controlled by epiphysis].
AB  - Rhythmical infradian oscillations of the activity of the sympatho-adrenal system,
      behavioural parameters, body mass and temperature, urination, and non-specific
      resistance were revealed in rats. It was found that the variable magnetic field
      with a frequency of 8 Hz and induction of 5 microT changed the infradian rhythms
      of the physiological parameters: i.e., the variable magnetic field induced the
      reorganization of integral rhythms, changed amplitudes, shifted phases of various
      rhythms and developed a desynchronosis. It was shown that the changes in the
      physiological systems under variable magnetic field influence can be displayed in
      the reorganization of the temporal organization only.

PMID- 9914840
TI  - [Intraday geo- and heliophysically significant periods in the integral rhythm of
      motor activity of animals].
AB  - The detailed structure of locomotor activity rhythm of rats in the ultradian
      range was investigated. The stability of discovered ultradian periods and their
      accordance to well-known periods of magnetic AE-index were estimated. It was
      revealed that a lot of geo- and heliophysically significant harmonics in the
      ultradian range with different stability are always present in the rhythm of
      locomotor activity. In most cases, the stable periods are daily harmonics. Such
      time organization is optimal for living organisms in case of simultaneous use of
      several "zeitgebers" of different nature, whose periods can substantially vary.

PMID- 9914841
TI  - [Hypoxic and antioxidant biological effect of multi-day application of a weak
      variable super-low frequency magnetic field].
AB  - There is an expressed effect of circulating anemia displayed after repeated and
      multiple prolonged influence of weak alternating magnetic fields of ultralow
      frequency on organisms of mouse, which causes hypoxia and other changes on the
      structure-metabolic level producing the increase of radioresistance.

PMID- 9914842
TI  - [Effect of geomagnetic activity on the human body in extreme conditions and
      correlation with data from laboratory observations].
AB  - It was hypothesized based on previous laboratory observations and theoretical
      concepts that astronauts working at the "Mir" station under zero gravity
      conditions exhibit enhanced sensitivity to geomagnetic disturbances. The result
      of studies made it possible to reveal the dynamics of changes in cardiovascular
      characteristics separately in the main phase and the phase of storm restoration.
      A similar dynamics of cardiac activity was observed in experimental rabbits
      during geomagnetic storms.

PMID- 9914843
TI  - [Effect of geomagnetic activity on the functional status of the body].
AB  - A complicated nonlinear biological system should be in principal more sensitive
      to the external factors activity including geomagnetic disturbances. The complex
      of experimental studies based on this hypothesis were done simultaneously in two
      hospitals in Moscow as well as in condition of space orbital station, where just
      above-mentioned conditions are the case. This studies revealed that the reaction
      of astronauts to the geomagnetic storm involves a mobilization and activation of
      all centers of the sympathetic link, and as a result,--a significant increase and
      stabilization of pulse (heart rate), decrease of the heart rhythm variability and
      the power of respiratory waves. This nonspecific adaptation stress-reaction was
      accompanied by variations in the regulation of vascular tonus which is correspond
      to specific adaptation stress-reaction. The results of clinical examinations of
      healthy people and patients with the ischemic heart disease lead us to the
      conclusion that the reaction to the geomagnetic disturbances are mainly of one
      type and manifests themselves in deterioration of the physiological status,
      rheologic blood characteristics and the heart rate disturbances similar to ones
      observed in astronautes.

PMID- 9914844
TI  - [Effect of passive screening for protecting patients with ischemic heart disease
      from the effect of geomagnetic disturbances].
AB  - The idea of shielding patients against, negative influence of geomagnetic
      disturbances was declared by A.L. Tchijevsky. The shielding chamber for patients
      with high sensitivity to geomagnetic variations was created in Central Railway
      Hospital in 1991. The positive effect of protection of patients with ischemic
      heart disease during magnetic storms was demonstrated.

PMID- 9914845
TI  - [Lethal manifestations of meteorological and cosmic factors].
AB  - Data on mortality in Moscow region during 1977 to 1996 reveal that total
      mortality per 1000 citizens is 3 to 4 times less than it occurred at the
      beginning of XX century. Catalogue of intense geomagnetic storms is compiled for
      1867 to 1996. Separation of data for geomagnetic-quiet and stormy years has shown
      that mortality during stormy years is increased by 30% as compared with quiet
      years. Seasonal variations of geomagnetic storms and mortality during quiet years
      reaches maxima near equinoxes but the peaks of mortality during stormy years are
      shifted towards the summer and winter. Lethal manifestations of the weather
      anomalies are less pronounced than the space storms: impact of precipitation
      anomalies on death-rate is negligible at the given area, the air temperature
      decrease is followed by enhancement of the death-rate by 10% during autumn while
      warming led to enhancement of the death-rate by 10% for winter, spring and summer
      and average for a year.

PMID- 9914846
TI  - [Effect of ionospheric parameters on the respiratory and cardiac system, function
      of the brain and higher nervous system activity in healthy people].
AB  - Effects of complex ionospheric parameters on the parameters of 4 systems of
      healthy people: respiration and cardiological systems, functions of brain and
      central neural activity, were studied. Results indicating the presence of highly
      significant multiple correlations of these biosystems with the complex of
      ionospheric parameters were received.

PMID- 9914847
TI  - [Medico-biological effect of natural electromagnetic variations].
AB  - Emergency ambulance statistical data accumulated in Moscow during March 1983
      October 1984 have been analyzed. Diurnal numbers of urgent hospitalization of
      patients in connection with suicides, mental disorders, myocardial infarction,
      defects of cerebrum vessels and arterial and venous diseases have been examined.
      Intensity and duration of planetary geomagnetic storms were used as magnetic
      activity indices. Comparison of geomagnetic and medical data rows has shown that
      at least 75% of magnetic storms caused increase in hospitalization of patients
      with the above-mentioned diseases on 30-80% at average. The dependence of the
      value of biotropic effect on the duration of effect and intensity of magnetic
      storm is observed.

PMID- 9914848
TI  - [Correlation of some indicators of intracellular energetics of nonpregnant and
      pregnant women with heliogeophysical and meteorological factors].
AB  - A cytochemical investigation of some characteristics of intracellular metabolism
      in blood leukocytes from 188 women (136 nonpregnant women with extragenital and
      genital pathologies and 53 pregnant women with pathology) at the age of 20 to 39
      was carried out. To assess the effect of heliogeophysical and meteorological
      factors on the intracellular metabolism, a correlation analysis was performed.

PMID- 9914849
TI  - [Effect of natural physical factors of the environment on the condition of
      pregnant women with normal pregnancy].
AB  - The enzymatic status of leukocytes with respect to succinate- and alpha
      glycerophosphate dehydrogenase activity, which reflects the degree of hypoxia in
      the organism is changed by 30% by the action of natural physical parameters of
      the environment. Using mathematical modelling, it was shown that the largest
      changes in the enzymatic status occur upon increased geomagnetic perturbations at
      a high atmospheric pressure. Chronic tissue hypoxia of the fetus and newborn is
      the most likely disease that can develop under these conditions. This is most
      important to expectant mothers older than 32 years. The effect of environmental
      influences is more pronounced during the second half of pregnancy.

PMID- 9914850
TI  - [Cosmic rays as the main factor affecting solar variability on climatic and
      atmospheric parameters].
AB  - Analysis of experimental data demonstrates that cosmic ray enhancement stimulates
      an increase of atmospheric aerosols and cloudiness. The study of solar proton
      events (SPE) has shown that during SPE one can observe increase in aerosol
      density by 1.2-1.4 times at 12-18 km altitudes. Such variations of aerosol
      density can be detected on global scale. Aerosol variations cause changes in
      integral atmospheric transparency which during disturbed periods can reach 5-6%.
      The atmospheric integral transparency variations are not less during the solar
      cycle on account of galactic cosmic ray variations. Atmospheric transparency
      variations creating the so-called "grey filter" for solar radiation should lead
      to surface temperature variations. During the periods of low solar activity under
      the influence of enhanced galactic cosmic ray fluxes, the density of the "grey
      filter" should increase and cause a decrease in surface temperatures,
      correspondingly. In frame of the physical mechanism considered the connection
      between solar cycle durations and surface temperature variations can be
      explained. In addition, one can understand the physical reason for the "Little
      Ice Age" appearance during Maunder minimum of solar activity, 2400 years
      periodicity of climatic processes, strong influence of the decrease in main
      geomagnetic field intensity on the development of Ice Age and Global Cooling.

PMID- 9914851
TI  - [Structure of the ecological year as a result of cosmophysical influences].
AB  - Some bases for the assumption are received that moment of the first after a
      spring equinox Sunday coming approximately on a full moon, marks a beginning of
      so-called ecological year. Any precise monthly laws are not revealed.

PMID- 9914852
TI  - [Effect of the approximately 2400-year solar climatic cycle on the lives of
      peoples].
AB  - 2400-year solar cycle ascertained by us in the long-term series of various
      natural characteristics (e.g. the radiocarbon content in samples of well-known
      ages, oscillations of the sea and ocean levels etc.) includes three parts roughly
      equal in duration: a phase of high activity, a phase of depression and a phase of
      moderate activity. In climate oscillations, which are connected with this cycle,
      the next phenomena are established: a little climatic optimum, a little Ice Age,
      and a temperate climate epoch.

PMID- 9914853
TI  - Mycophenolate mofetil: therapeutic applications in kidney transplantation and
      immune-mediated renal disease.
AB  - The immunosuppressant mycophenolate mofetil (MMF) inhibits the enzyme inosine-5'
      monophosphate dehydrogenase and thus interferes with cellular GTP synthesis. MMF
      suppresses the cellular and humoral immune response and has antiproliferative
      effects on vascular smooth muscle and mesangial cells in vitro and in vivo. In
      large multicenter trials with almost 1500 patients MMF has been proven highly
      efficacious for transplant rejection prophylaxis with the main side-effects of
      gastrointestinal disorders and a slightly increased incidence of viral
      infections. Recent investigations suggest MMF as an alternative immunosuppressant
      in cyclosporin A nephrotoxicity. Preliminary observations show promising results
      for MMF in the treatment of autoimmune-mediated renal disease. The rationale for
      its use in this patient group and evidence from experimental studies are
      discussed. As current therapy of this disease entity is still unsatisfactory,
      future clinical trials are necessary to investigate the efficacy and safety of
      MMF for this new indication.

PMID- 9914854
TI  - Developmental nephrology comes of age.

PMID- 9914855
TI  - Integrins and the kidney: biology and pathobiology.
AB  - Integrins represent a superfamily of cell surface molecules that are important
      mediators of cell-extracellular matrix interactions. Of the many known integrin
      subunit combinations, only a few (alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1,
      alpha 6 beta 1, alpha 8 beta 1 and alpha v beta 3) appear to play significant
      roles in renal development and function. The current understanding of these roles
      is reviewed. Potential therapeutic benefits from the alteration of integrin
      function by arginine-glycine-aspartic acid peptides in renal ischemic injury have
      been suggested. Reduced tubular obstruction is a potential mechanism, however
      other mechanisms remain to be explored. Finally, recent studies suggest a
      mechanism whereby abnormal interactions between integrins and non-specifically
      glycosylated glomerular basement membrane components could be involved in the
      pathogenesis of diabetic nephropathy. The elucidation of other potential
      pathophysiological roles for integrins in renal disease has just begun.

PMID- 9914856
TI  - Molecular mechanisms of cell death and regeneration in acute ischemic renal
      injury.
AB  - Acute renal failure continues to have an unacceptably high mortality rate.
      Ischemic renal injury is the most common cause of acute renal failure.
      Understanding the molecular mechanisms of cell death and regeneration is
      important for designing future therapeutic strategies. Recent interest in our
      laboratory has focused on molecular response after ischemic renal injury and, in
      particular, genes that are important in cell death and repair after ischemia. The
      identification of genes that are differentially expressed after ischemia has led
      to new information regarding the identity of possible mediators of cell death and
      regeneration in renal tubular epithelial cells.

PMID- 9914857
TI  - The transforming growth factor beta system in kidney disease and repair: recent
      progress and future directions.
AB  - Transforming growth factor beta is a multifunctional polypeptide growth factor
      implicated in a variety of renal diseases. The expression of transforming growth
      factor beta is enhanced in renal diseases and available evidence suggests that
      its activity in promoting the synthesis of extracellular matrix plays a crucial
      role in fibrotic deposition and the decline in renal function. Transforming
      growth factor beta is, however, also expressed in response to renal injury and
      may play an important role in normal repair processes. It appears that renal
      diseases may result from the inappropriate regulation of transforming growth
      factor beta expression. The determination of the factors that mediate
      transforming growth factor beta activity will be of primary importance in
      elucidating the mechanisms leading to renal disease or repair after injury. Both
      in-vitro and in-vivo studies have demonstrated that proteolytic activity,
      thrombospondin-1, elevated glucose, angiotensin II, oxidant stress and
      hemodynamic forces regulate transforming growth factor beta activity through both
      transcriptional and post-transcriptional mechanisms. In some cases, therapies
      that may partly disrupt renal transforming growth factor beta activity have shown
      promise in slowing the progression to end-stage renal disease.

PMID- 9914858
TI  - Cell localization and ontogeny of sodium transport pathways in the distal
      nephron: perspectives in function and failure.
AB  - The expression and function of ion co-transporters/exchangers/channels in the
      distal nephron have recently been defined. The role of cation-chloride co
      transporters and proteins implicated in aldosterone target cell function are
      reported in the adult and during ontogeny. Volume disorders can currently be
      related to identified gene products acting in defined nephron sites.

PMID- 9914859
TI  - Role of retinoids in renal development: pathophysiological implication.
AB  - Vitamin A closely modulates nephron endowment at birth. It is also required for
      the development of renal vasculature. Fetal vitamin A status may thus be
      responsible for most of the variations in nephron number found in the general
      population, and may play a major role in the intrauterine programming of chronic
      renal disease and hypertension.

PMID- 9914860
TI  - Molecular and cellular determinants of mineralocorticoid selectivity.
AB  - Aldosterone plays a major role in the regulation of renal sodium reabsorption, of
      extracellular fluid volume and blood pressure. Such specific mineralocorticoid
      physiological adaptations occur despite the large prevalence of glucocorticoid
      hormones over aldosterone in the plasma. Indeed both classes of hormones bind
      with the same affinity to the mineralocorticoid receptor, but several mechanisms
      allow selective and tissue-specific aldosterone effects. They represent a series
      of mutually interacting selectivity filters, which have not yet been fully
      documented. The main determinants of aldosterone selective effects include an
      enzymatic protection of the mineralocorticoid receptor, the intrinsic properties
      of the mineralocorticoid receptor towards different ligands, and numerous
      possibilities of interaction between corticosteroid receptors (forming different
      homo or heterodimers) and other transcription factors.

PMID- 9914861
TI  - Intracellular localization and activation of endothelial nitric oxide synthase.
AB  - Nitric oxide production by the Ca2+/calmodulin-dependent enzyme endothelial
      nitric oxide synthase primarily reflects changes in intracellular [Ca2+],
      increasing as Ca2+ rises and decreasing as Ca2+ falls. This simplistic bimodal
      mechanism of regulation has recently been refined by the finding that the binding
      of Ca2+/calmodulin to endothelial nitric oxide synthase involves the disruption
      of the association of endothelial nitric oxide synthase from the scaffolding
      protein caveolin and the subsequent translocation of the enzyme from plasmalemmal
      caveolae. Moreover, other endothelial nitric oxide synthase-associated proteins
      could account for a delayed Ca(2+)-independent activation of nitric oxide
      production, and may be involved with caveolin in the reversible trafficking of a
      large endothelial nitric oxide synthase-containing heterocomplex between the
      caveolae and cytosolic cell structures.

PMID- 9914862
TI  - Neural mechanisms in nitric-oxide-deficient hypertension.
AB  - Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic
      nervous outflow, and deficient neuronal nitric oxide production to cause
      sympathetic overactivity, which then contributes to nitric-oxide-deficient
      hypertension. The biochemical and neuroanatomical basis for this concept revolves
      around nitric oxide modulation of glutamatergic neurotransmission within
      brainstem vasomotor centers. The functional consequence of neuronal nitric oxide
      in blood pressure regulation is, however, marked by an apparent conflict in the
      literature. On one hand, conscious animal studies using sympathetic blockade
      suggest a significant role for neuronal nitric oxide deficiency in the
      development of nitric-oxide-deficient hypertension, and on the other hand, there
      is evidence against such a role derived from 'knock-out' mice lacking nitric
      oxide synthase 1, the major source of neuronal nitric oxide.

PMID- 9914863
TI  - Nitric oxide synthase gene transfer to the vessel wall.
AB  - A wide array of vascular disorders have been shown to benefit from gene therapy.
      Given the vasoprotective role that nitric oxide plays in the vasculature, it is
      understandable why gene therapy with the three different isoforms of nitric oxide
      synthase has been so successful. This review summarizes the current literature
      pertaining to nitric oxide synthase gene transfer to the vascular wall.

PMID- 9914864
TI  - Nitric oxide synthase gene polymorphism and its influence on cardiovascular
      disease.
AB  - Several lines of evidence indicate a significant association between variations
      of the endothelial constitutive nitric oxide synthase gene and the incidence of
      cardiovascular disease, and discrepant findings may be attributable to racial
      differences. The detection of functional allelic polymorphisms may be needed to
      confirm this association, because direct evidence to support a causative role for
      the endothelial constitutive nitric oxide synthase gene is not yet available.
      There are no available data to confirm that neural and inducible nitric oxide
      synthases are associated with cardiovascular diseases.

PMID- 9914865
TI  - Effects of cytokines on nitric oxide pathways in human vasculature.
AB  - Proinflammatory cytokines exert a number of important effects on vascular
      reactivity. At one end of the spectrum, certain cytokines may induce vascular
      paresis leading to profound vasodilatation and hyporesponsiveness to constrictor
      stimuli. This may be relevant to the pathogenesis of septic shock and other types
      of inflammatory vasodilatation. At the other end of the spectrum, inflammatory
      cytokines can impair endothelium-dependent dilatation and the endothelium may
      lose its ability to respond to circulating hormones or autacoids. This effect may
      case a predisposition to vessel spasm, thrombosis or atherogenesis. Studies in
      human vessels suggest that interleukin-1 is particularly important as a mediator
      of inflammatory dilatation; the underlying mechanisms include induction of the
      inducible isoform of nitric oxide synthase in vascular smooth muscle, or over
      production of nitric oxide from the endothelial isoform of nitric oxide synthase.
      Induction of the enzyme GTP cyclohydrolase 1 and consequent production of
      tetrahydrobiopterin contributes to the increase in the activity of endothelial
      nitric oxide synthase. In contrast, tumour necrosis factor-alpha considerably
      impairs endothelium-dependent relaxation. The mechanisms of these effects are not
      yet fully understood, but tumour necrosis factor can induce endothelial
      dysfunction in human endothelial cells in culture, and human blood vessels in
      vitro and in vivo. The implications of these observations for cardiovascular
      disease are discussed.

PMID- 9914867
TI  - Hormones, autacoids, neurotransmitters and growth factors.

PMID- 9914866
TI  - Nitric oxide as a regulator of tissue oxygen consumption.
AB  - Nitric oxide originating from the microvascular endothelium and other tissue
      sources appears to play an important physiological role in the regulation of
      mitochondrial respiration in vivo. Physiological processes and pathophysiological
      conditions that influence the production and action of nitric oxide are likely to
      alter the control of tissue respiration by nitric oxide. Oxidant stress
      associated with the production of peroxynitrite from nitric oxide, under
      conditions such as hypoxia-reoxygenation, convert the reversible inhibition of
      respiration by nitric oxide into an irreversible process, which is potentially an
      important contributor to the expression of alterations in physiological function
      and tissue injury.

PMID- 9914868
TI  - Circulation and hemodynamics.

PMID- 9914869
TI  - Leukemia.

PMID- 9914870
TI  - Advances in the biology and treatment of multiple myeloma.
AB  - Advances in the understanding of the cellular and molecular derangements involved
      in the initiation and progression of multiple myeloma are beginning to be
      translated into novel therapeutic approaches. The myeloma stem cell has been
      under intense scrutiny regarding its normal B-cell counterpart. Oncogenes, tumor
      suppressor genes, and cell-survival genes have all been found to be dysregulated
      in some myeloma patients. Growth factors, especially interleukin-6, appear to be
      critical for disease progression, and interruption of autocrine and paracrine
      loops has been achieved with resultant inhibition of myeloma cell growth.
      Mechanisms of drug resistance and the implications of the multidrug resistance
      phenotype are just beginning to be understood. High-dose therapeutic regimens
      with autologous peripheral blood stem cell or allogeneic bone marrow rescue are
      rigorously being studied with an emphasis on exploiting the graft-versus-myeloma
      effect. Pamidronate, a second-generation bisphosponate, has been shown to be
      effective at decreasing adverse skeletal events in patients with advanced
      myeloma. The topoisomerase 1 inhibitor, topotecan, has shown activity in an
      initial study.

PMID- 9914871
TI  - The biology and treatment of acute progranulocytic leukemia.
AB  - Acute progranulocytic leukemia (APL) is one of the most curable of all human
      cancers. Combination treatment with retinoic acid (RA) and anthracycline-based
      chemotherapy is safe and effective for the vast majority of patients, and several
      novel treatment approaches are under investigation for high-risk or relapsed
      patients. The APL-specific oncogenes PML-RAR alpha and PLZF-RAR alpha both bind
      nuclear corepressors and recruit histone deacetylase activity to promoters of RA
      target genes. The differential sensitivity of binding of these oncogenes to
      nuclear corepressors in the presence of RA appears to explain the resistance of
      PLZF-RAR alpha-related APL to RA and at the same time explains the effectiveness
      of RA in PML-RAR alpha-positive APL. Transcriptional repression of RA target
      genes, mediated by histone deacetylase activity, may thus be a key pathogenetic
      event in APL. Cure of the minority of resistant patients requires further
      refinement of current treatment approaches and appropriately timed incorporation
      of novel therapies, such as arsenic trioxide or histone deacetylase inhibitors.

PMID- 9914872
TI  - Tailoring the treatment of acute myeloid leukemia.
AB  - For younger patients with acute myeloid leukemia (AML), the current priority is
      to prevent disease relapse. Intensification of induction has been shown to
      achieve this. Several randomized trials have been conducted to evaluate the role
      of autografting in AML. All trials reduce the risk of relapse but do not
      necessarily improve the survival, either because the competing effects of
      procedural mortality or salvage after relapse balance the benefits. Patients with
      different risk profiles may have different treatment plans. In older patients,
      progress is difficult to detect. Overcoming inherent drug resistance is of
      current interest, while improving supportive care by the routine use of growth
      factors has been disappointing.

PMID- 9914873
TI  - The causes of acute leukemia.
AB  - Although impressive biologic advances have increased understanding of
      leukemogenesis, we know little about the causes of the acute leukemias.
      Epidemiologic studies have focused primarily on children. Higher birth weight is
      associated with an increased risk of childhood acute leukemia. Several theories
      have been advanced that may account for these observations, and additional
      biologic studies are needed. Some epidemiologic studies suggest that the acute
      leukemias in children may have an infectious component. Again, further work,
      especially in the area of specific causative agents, is necessary. Another area
      for future epidemiologic study includes investigation of exposure to natural and
      synthetic DNA topoisomerase II inhibitors. Preliminary evidence suggests that
      exposure to these agents, which are found in certain foods and medications, may
      be related to the subsequent development of acute leukemia in infants.

PMID- 9914874
TI  - Diagnosis and therapy for pituitary tumors.
AB  - This article focuses on developments in treatment options for pituitary adenomas.
      We review the literature on the advances in diagnosis and treatment modalities,
      including medical and surgical approaches. We also discuss conventional radiation
      and the recently proposed genetic treatments for pituitary tumors.

PMID- 9914875
TI  - Recent advances in systemic therapy for gastrointestinal neuroendocrine tumors.
AB  - Neuroendocrine tumors of the gastrointestinal tract are rare tumors which can be
      classified as amine precursor uptake and decarboxylation tumors (APU-Domas).
      Although the majority of clinically apparent tumors are malignant, they are
      frequently slow growing. Despite this characteristic, they may generate disabling
      hormonal syndromes requiring aggressive treatment to achieve palliation. Recent
      advances in understanding the pathophysiology of these tumors has led to better
      medical therapy with chemotherapeutic agents, somatostatin analogues, and
      biologic therapies. This review will update the recent efforts in systemic
      therapies of the gastrointestinal neuroendocrine tumors.

PMID- 9914876
TI  - Embolization and chemoembolization therapy for neuroendocrine tumors.
AB  - Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have
      a predisposition for metastasizing to the liver. In such patients, the clinical
      course is often dominated by the hepatic disease, either because of hormone
      secretion or because of tumor bulk. Because the liver has a dual vascular supply
      and hepatic metastases derive the majority of blood from the hepatic artery, the
      regional delivery of chemotherapy can offer pharmacokinetic advantages over
      systemic administration. The hepatic artery is also a nonsurgical avenue for
      inducing selective metastasis ischemia by the embolization of tumor vessels. The
      combination of these two therapies, or chemoembolization, may provide additive
      benefits. Such an approach has been demonstrated to reduce tumor bulk, reduce
      hormone levels, and palliate the symptoms of many patients with liver-dominant
      neuroendocrine metastases. Embolization or chemoembolization is an appropriate
      modality for some patients with neuroendocrine tumors.

PMID- 9914877
TI  - Advances in the pathogenesis and treatment of thyroid cancer.
AB  - Thyroidectomy remains the mainstay of treatment for thyroid carcinoma. The extent
      of surgical resection, however, remains controversial as most patients will have
      excellent long-term prognosis and because some of the standard staging and
      prognostic information are not available at the time of surgical resection. The
      different staging and risk group definitions for thyroid carcinoma are not
      superior to the Tumor-Node-Metastasis classification of the American Joint
      Commission in Cancer (AJCC), which is universally available and accepted and
      should be used to report treatment outcomes. Recent advances in the molecular
      pathogenesis of thyroid malignancy will help identify high-risk patients who
      would benefit from aggressive surgical resection and adjuvant treatment.

PMID- 9914878
TI  - Cancer biology.

PMID- 9914880
TI  - Three molecular determinants of malignant conversion and their potential as
      therapeutic targets.
AB  - The past decade has been marked by an explosion of knowledge regarding the
      dysregulation of cancer at the molecular level. It has become apparent that
      oncogenes, tumor suppressor genes, and other ancillary molecules interact in
      complex pathways that govern cellular homeostasis. We review three molecular
      events that have been implicated in tumorigenesis and define pathways ripe for
      the development of new therapeutic approaches: 1) activation of telomerase, 2)
      dysregulation of the patched/sonic hedgehog pathway, and 3) mutation of the INK4
      alpha-ARF locus.

PMID- 9914881
TI  - Mechanisms of apoptosis avoidance in cancer.
AB  - Defects in the programmed cell death mechanisms can extend cell lifespan,
      contributing to neoplastic cell expansion independently of cell division.
      Deficiencies in apoptosis also contribute to carcinogenesis by creating a
      permissive environment for genetic instability and accumulation of gene
      mutations, permitting disobeyance of cell cycle checkpoints which would normally
      induce apoptosis, facilitating growth factor- and hormone-independent cell
      survival, supporting anchorage-independent survival during metastasis, reducing
      dependence on oxygen and nutrients, promoting resistance to immune-based
      destruction, and conferring resistance to cytotoxic anticancer drugs and
      radiation. Though much remains to be learned, identification of gene families
      that control the physiological cell death pathway has provided the basis for
      improved understanding of tumor biology. This review describes some of the recent
      progress made towards delineating the biochemistry and molecular biology of
      apoptosis control, and briefly summarizes the progress in identifying specific
      road blocks to apoptosis induction in cancers. These advances are beginning to
      reveal novel strategies for combating cancer by restoring apoptosis sensitivity.

PMID- 9914882
TI  - Genomics and array technology.
AB  - Genome projects are providing vast amounts of sequence data. This raw material
      makes possible a completely new era of experimental approaches. Among these, DNA
      array technology, which allows one to assay thousands of unique nucleic acid
      samples simultaneously, will be important in genomic research, and the results of
      this research are likely to affect virtually every field of biology. DNA array
      technology is still in its infancy, but many have demonstrated its power by using
      it for such diverse applications as global monitoring of gene expression,
      mutation detection, and genetic mapping.

PMID- 9914879
TI  - Developing recombinant and synthetic vaccines for the treatment of melanoma.
AB  - To develop new vaccines for the treatment of patients with cancer, target
      antigens presented on tumor cell surfaces have been cloned. Many of these
      antigens are non-mutated differentiation antigens and are expressed by virtually
      all melanomas, making them attractive components for a widely efficacious
      melanoma vaccine. These antigens are also expressed by melanocytes, however, and
      are likely to be subject to immune tolerance. A central challenge for tumor
      immunologists has thus been the breaking of tolerance to cancer antigens. We
      review recent clinical trials using experimental cancer vaccines, including
      recent evidence that therapeutic vaccines can induce objective responses in
      patients with metastatic malignant melanoma. We focus on the foundations of these
      approaches in new experimental animal models designed to test novel vaccines and
      report on what these new models predict for the future development of therapeutic
      vaccines for cancer.

PMID- 9914883
TI  - Bibliography. Current world literature. Leukemia.

PMID- 9914884
TI  - Bibliography. Current world literature. Endocrine tumors.

PMID- 9914885
TI  - Bibliography. Current world literature. Cancer biology.

PMID- 9914886
TI  - [Shampoos: composition and clinical applications].
AB  - Shampooing is the most common form of hair treatment. Shampoos have primarily
      been products aimed at cleansing the hair and scalp. The diversity of qualities
      demanded from a good shampoo by today's consumer go far beyond this general
      function. A cosmetic benefit is expected, and the shampoo formulation has to be
      tailored to all the possible variations associated with hair quality (dry,
      greasy, permed, bleached, dyed), age (baby shampoo), care habit (frequency of
      shampooing) and specific problems relating to the superficial condition of the
      scalp (dandruff, seborrhea). Selected ingredients of shampoos that have been
      popular with the consumer are currently under attack because of potential risks
      associated with their use (e.g. halogenated organic compounds, formaldehyde, musk
      fragrances, and crude coal tar). Our standard graduate training programs devote
      limited attention to the subject of shampoos, and much of the readily available
      information concerning shampoos is supplied by the industry. We should be
      increasingly aware that our patients look to us to supply independent information
      on what can be expected from a shampoo to enable them to make more informed
      choices at the consumer level.

PMID- 9914887
TI  - [Cutaneous Staphylococcus aureus colonisation of atopic eczema. Mechanisms,
      pathophysiological importance and therapeutic consequences].
AB  - Mechanisms for the increased Staphylococcus aureus colonization in atopic eczema
      are only partially known. From the aspect of the bacterium, the presence of
      various extracellular matrix components seems important. In the host epidermal
      lipid deficencies disturbing barrier dysfunction are important. Staphylococcus
      aureus' immunological and inflammatory effects include the release of
      superantigens, additional exotoxins and exoenzymes and perhaps bacterial DNA
      triggered mechanisms. Therapeutic possibilities include the use of systemic
      antibiotics in cases of generalized superinfected atopic eczema, the use of
      corticosteroids and specific antibiotic-antiseptic combinations in cases of
      localised superinfected atopic eczema and the wide-spread use of topical
      antiseptics in cases of microbial-laden atopic eczema.

PMID- 9914888
TI  - [Remission ratio of chronic urticaria--"spontaneous" healing or result of
      eradication of Helicobacter pylori?].
AB  - Helicobacter pylori infection has been assumed to be the underlying cause of some
      dermatological diseases such as, chronic urticaria. In order to investigate this
      problem we interviewed 55 patients with chronic urticaria concerning the state of
      the disease approximately 10 months after being discharged from hospital. After
      an additional six months we interviewed them for a second time and thus
      determined the remission ratio. There was no significant evidence showing that a
      link exists between urticaria and proven Helicobacter pylori infection (chi 2
      Test). There was also no significant correlation in the remission ratio between
      patients treated with a triple therapy and non-treated patients (exact Fisher
      Test).

PMID- 9914889
TI  - [Supplementary history and occupational dermatologic evaluation of medical bath
      workers, masseurs, and physical therapists].
AB  - The various noxious agents to which these occupational groups can be exposed are
      described in detail. We have constructed a supplementary questionnaire to aid the
      occupational dermatologist in evaluating such individuals. We describe measures
      for skin protection, and methods for reduce exposure of harmful agents.

PMID- 9914890
TI  - [Adult-onset Still's disease and its characteristic rash].
AB  - Still's disease was originally described as one form of rheumatoid arthritis in
      children beginning with fever and other systemic symptoms. In rare cases it may
      also begin in the adult and is then referred to as adult-onset Still's disease.
      The diagnostic criteria include typical rash, arthralgias, bouts of fever, and
      leukocytosis, as well as lymphadenopathy or splenomegaly, liver dysfunctions,
      noninfectious angina, and absence of rheumatoid factor and antinuclear
      antibodies. We report two adult patients with longstanding disease whose
      exanthema guided us to the correct diagnosis. The rash is a finding with high
      sensitivity. It is characterized by red macules with distinct borders and is
      evanescent. During an acute flare of the rash, gentle friction induces
      erythematous, isomorphic (Koebner) phenomena, which, as we describe here for the
      first time, may persist longer than the remainder of the fleeting rash.

PMID- 9914891
TI  - [Trichoadenoma of Nikolowski--review of four decades and seven new cases].
AB  - Trichoadenoma of Nikolowski is a rare, benign, well differentiated, slowly
      growing tumor of the hair follicle which was first described in 1958 by
      Nikolowski. 26 cases reported in the literature since then and our seven cases
      show the following features: a tumor of adults, mostly in the face (57.5%) or
      buttocks (24.2%), size in general 0.5-1.5 cm, no sex preference. According its
      morphological differentiation, trichoadenoma is situated between a
      trichofolliculoma and a trichoepithelioma. The clinical appearance is,
      misleading, suggesting the diagnosis of basal cell carcinoma or epidermal cyst.

PMID- 9914892
TI  - [Scabies--provoked bullous lichen planus in a child].
AB  - Lichen ruber planus is considered a T-cell mediated immunologic reaction with
      unclear pathogenesis. Drugs and infections (especially hepatitis B and C) are
      well-known provocation factors. After an infection with scabies a 13 year old boy
      developed a generalized lichen planus including bullous lesions. For the first
      time scabies is presented as a trigger for lichen planus. In childhood, lichen
      planus is characterized by atypical clinical features and sometimes a severe
      course.

PMID- 9914893
TI  - [Persistent erythema and edema of the face associated with rosacea and lymph
      vessel dysplasia].
AB  - A 24-year-old woman with lymph vessel dysplasia had experienced a progressive
      edema of her legs since her second year of life and progressive facial edema for
      the past year. She also had telangiectasias and papules on the background of a
      diffuse erythema as well as marked seborrhea on her face. Histopathological
      examination of a representative facial lesion revealed a granulomatous dermatitis
      with periadnexal distribution mainly consisting of lymphocytes and histiocytes.
      In addition, there was a moderate fibrosis of the dermis with numerous mast
      cells. By duplex ultrasound, a diagnosis of a massive edema of the legs without
      evidence for chronic venous insufficiency was made. The clinical and
      histopathological findings were consistent with solid persistent erythema and
      edema of the face associated with rosacea and lymph vessel dysplasia. The chronic
      course, absence of serological abnormalities and nonspecific histopathological
      features as well as resistance to therapy are the most important diagnostic
      criteria of this disease also known as Morbihan's disease.

PMID- 9914894
TI  - [Comments on the work of H.M. Ockenfels, U. Seeman, M. Goos "Contact dermatitis
      in housewives." Hautarzt (1998) 49:280-290].

PMID- 9914895
TI  - [Comment on the work of P.H. Hoger: "Topical antibiosis and antisepsis." Hautarzt
      (1998) 49:331-347].

PMID- 9914896
TI  - [Ultrasound of the lymph nodes and the subcutis in dermatology. Part 1].

PMID- 9914897
TI  - [Pathogenesis research with clinical application. Successful treatment of Lyell's
      syndrome with intravenous immunoglobulin].

PMID- 9914898
TI  - Churchill and the immune system of ectothermic vertebrates.

PMID- 9914899
TI  - The phylogeny and evolution of the thioester bond-containing proteins C3, C4 and
      alpha 2-macroglobulin.
AB  - The complement system is an effector of both the acquired and innate immune
      systems of the higher vertebrates. It has been traced back at least as far as the
      echinoderms and so predates the appearance of the antibodies, T-cell receptors
      and MHC molecules of adaptive immunity. Central to the function of complement is
      the reaction of the thioester bond located within the structure of complement
      components C3 and C4. The structural thioester first appeared in a protease
      inhibitor, alpha 2-macroglobulin, in which it is involved in the immobilisation
      and entrapment of proteases. An important development in the C3 molecule has been
      the acquisition of a catalytic His residue which greatly increases the rate of
      reaction of the thioester with hydroxyl groups and with water.

PMID- 9914900
TI  - Structural and functional identification of complement components of the bony
      fish, carp (Cyprinus carpio).
AB  - Complement is a humoral factor of innate immunity and plays important roles in
      immune surveillance and clearance of invading pathogens. Mammalian complement
      consists of the classical (antibody-dependent), the alternative (antibody
      independent) and the lectin (triggered by mannose-binding lectin) pathways of
      activation, and of the lytic pathway. Phylogenetically, bony fish are one of the
      lowest groups of vertebrates with serum that shows hemolytic activity
      indistinguishable from that of mammalian complement. In our series of trials to
      address the question "How many components constitute the bony fish complement?"
      Functional analyses, protein isolation, and molecular cloning revealed the
      presence of major components constituting each pathway, the similarity between
      bony fish and mammalian complement being considerable. Recent investigations on
      carp (Cyprinus carpio) and other fish species revealed striking features unique
      to bony fish complement, including a remarkable diversity in structure and
      function of the third component, C3, and the presence of a newly identified
      lineage in evolution of the factor B and C2 family. For a significant insight
      into the evolution of complement systems and clinical applications to aquaculture
      industry, further extended studies are warranted.

PMID- 9914901
TI  - Evolution and diversity of the complement system of poikilothermic vertebrates.
AB  - In mammals the complement system plays an important role in innate and acquired
      host defense mechanisms against infection and in various immunoregulatory
      processes. The complement system is an ancient defense mechanism that is already
      present in the invertebrate deuterostomes. In these species as well as in
      agnathans (the most primitive vertebrate species), both the alternative and
      lectin pathway of complement activation are already present, and the complement
      system appears to be involved mainly in opsonization of foreign material. With
      the emergence of immunoglobulins in cartilaginous fish, the classical and lytic
      pathways first appear. The rest of the poikilothermic species, from teleosts to
      reptilians, appear to contain a well-developed complement system resembling that
      of homeothermic vertebrates. However, important differences remain. Unlike
      homeotherms, several species of poikilotherms have recently been shown to possess
      multiple forms of complement components (C3 and factor B) that are structurally
      and functionally more diverse than those of higher vertebrates. It is noteworthy
      that the multiple forms of C3 that have been characterized in several teleost
      fish are able to bind with varying efficiencies to various complement-activating
      surfaces. We hypothesize that this diversity has allowed these animals to expand
      their innate capacity for immune recognition.

PMID- 9914902
TI  - Molecular genetics of the complement C3 convertases in lower vertebrates.
AB  - Evolution of the two gene families of the complement system involved in the
      formation of the C3 convertases, B/C2 and C3/C4/C5, was studied at the cDNA level
      in lower vertebrates. Cyclostomes, the most primitive extant vertebrates, seem to
      possess only one member each of these families, indicating that gene duplication
      between B and C2 or among C3, C4 and C5 occurred in the lineage of jawed
      vertebrates. Typical C3 and C4 cDNAs were identified in both amphibian (Xenopus)
      and teleost (medaka fish), locating the C3/C4 gene duplication before the
      divergence of ray-finned fish and lobe-finned fish. On the other hand, typical B
      cDNA was identified in Xenopus, whereas teleost counterparts from three species
      all showed intermediate character between B and C2, suggesting the possibility
      that the B/C2 gene duplication occurred in the tetrapod lineage. Genetic linkage
      between these two family genes within the MHC was observed in Xenopus but not in
      medaka fish.

PMID- 9914903
TI  - Shark complement: an assessment.
AB  - The classical (CCP) and alternative (ACP) pathways of complement activation have
      been established for the nurse shark (Ginglymostoma cirratum). The isolation of a
      cDNA clone encoding a mannan-binding protein-associated serine protease (MASP)-1
      like protein from the Japanese dogfish (Triakis scyllia) suggests the presence of
      a lectin pathway. The CCP consists of six functionally distinct components: C1n,
      C2n, C3n, C4n, C8n and C9n, and is activated by immune complexes in the presence
      of Ca++ and Mg++ ions. The ACP is antibody independent, requiring Mg++ ions and a
      heat-labile 90 kDa factor B-like protein for activity. Proteins considered
      homologues of C1q, C3 and C4 (C2n) of the mammalian complement system have been
      isolated from nurse shark serum. Shark C1q is composed of at least two chain
      types each showing 50% identity to human C1q chains A and B. Partial sequence of
      the globular domain of one of the chains shows it to be C1q-like rather than like
      mannan-binding protein. N-terminal amino acid sequences of the alpha and beta
      chain of shark C3 and C4 molecules show significant identity with corresponding
      human C3 and C4 chains. A sequence representing shark C4 gamma chain, shows
      little similarity to human C4 gamma chain. The terminal shark components C8n and
      C9n are functional analogues of mammalian C8 and C9. Anaphylatoxin activity has
      been demonstrated in activated shark serum, and porcine C5a desArg induces shark
      leucocyte chemotaxis. The deduced amino acid sequence of a partial C3 cDNA clone
      from the nurse shark shows 50%, 30% and 24% homology with the corresponding
      region of mammalian C3, C4 and alpha 2-macroglobulin. Deduced amino acid sequence
      data from partial Bf/C2 cDNA clones, two from the nurse shark and one from the
      Japanese dogfish, suggest that at least one species of elasmobranch has two
      distinct Bf/C2 genes.

PMID- 9914904
TI  - Towards understanding the evolutionary origins and early diversification of
      rearranging antigen receptors.
AB  - The rearranging antigen binding receptors, immunoglobulin heavy (IgH) and light
      (IgL) chains and the four classes of T-cell antigen receptors (TCR) are found in
      all contemporary species of jawed vertebrates examined thus far. Ig genes have
      undergone marked changes in organization and mechanisms of diversification during
      vertebrate phylogeny; whereas TCR genes, which are found in species as
      phylogenetically removed as man and cartilaginous fishes (e.g. skate), are
      generally similar in terms of structure, diversification and, presumably,
      function. The patterns of Ig divergence in cartilaginous fish are informative as
      to both the potential for genetic variation and the mechanisms that bring about
      such change. No evidence has been found for homologs of either Ig, TCR,
      recombination activating gene (RAG)1 or RAG2 in jawless vertebrates or
      invertebrates. Thus, a phylogenetic demarcation exists in terms of the presence
      and absence of the rearranging antigen binding receptor genes. It is presumed
      that the rearranging antigen binding receptors arose from a non-rearranging
      predecessor. The recent discovery of non-rearranging homologs of antigen binding
      receptor genes in several species offers insight into alternative forms of
      recognition, relationships between adaptive and innate mechanisms of immunity,
      and the origins of antigen recognition.

PMID- 9914905
TI  - T-cell receptors in ectothermic vertebrates.
AB  - The structure and expression of genes encoding molecules homologous to mammalian
      T-cell receptors (TCR) have been recently studied in ectothermic vertebrate
      species representative of chondrychthians, teleosts, and amphibians. The overall
      TCR chain structure is well conserved in phylogeny: TCR beta- and TCR alpha-like
      chains were detected in all the species analyzed; TCR gamma- and TCR delta-like
      chains were also present in a chondrychthian species. The diversity potential of
      the variable (V) and joining (J) segments is rather large and, as in mammals,
      conserved diversity (D) segments are associated to the TCR beta and TCR delta
      chains. An important level of junctional diversity occurred at the V-(D)-J
      junctions, with the potential addition of N- and P-nucleotides. Thus, the
      conservation of the structure and of the potential of diversity of TCR molecules
      have been under a permanent selective pressure during vertebrate evolution. The
      structure of MHC class I and class II molecules was also well conserved in jawed
      vertebrates. TCR and MHC molecules are strongly functionally linked and play a
      determinant role in the initiation and the regulation of the specific immune
      responses; thus, it is not surprising that their structures have been
      reciprocally frozen during evolution.

PMID- 9914906
TI  - Antibodies of sharks: revolution and evolution.
AB  - The combinatorial immune response is restricted to jawed vertebrates with
      cartilaginous fishes being the lowest extant species to have the mechanism for
      diversification and an extensive panoply of immunoglobulins, T-cell receptors and
      MHC products. Here, we review the molecular events of the "big bang" or rapid
      evolutionary appearance of the functionally complete combinatorial immune system
      coincident with the appearance of ancestral jawed vertebrates, suggesting that
      this event was catalyzed by horizontal transfer of DNA processing systems. We
      analyze the nature and extent of variable and constant domain diversity among the
      distinct immunoglobulin sets of carcharhine sharks focusing upon the lambda-like
      light chains and the mu and omega heavy chains. The detection and isolation of
      natural antibodies from the blood of unimmunized sharks illustrates a surprising
      range of recognition specificities and the existence of polyspecificity suggests
      that the antibody-forming system of sharks offers unique opportunities for
      studies of immunological regulation. Although the homologies between shark and
      mammalian immunoglobulins are unequivocal, major differences in segmental gene
      organization present challenges to our understanding of basic immunological
      phenomena such as clonal restriction.

PMID- 9914908
TI  - Varied redox forms of teleost IgM: an alternative to isotypic diversity?
AB  - Teleosts (bony fish) are thought to primarily or exclusively possess a single
      structural form of immunoglobulin (Ig), a tetrameric IgM. However, in species
      wherein intact Ig has been electrophoretically analyzed under denaturing, non
      reducing conditions, a significant degree of structural diversity has been
      revealed. This IgM molecule appears to be assembled with great latitude in the
      degree of disulfide crosslinking between monomeric or halfmer subunits composing
      the complete IgM molecule. This heterogeneity in the basic structure (herein
      referred to as redox forms) is not due to isotypic differences as each B cell
      produces this heterogeneity within its immunoglobulin product. Additionally, in
      the case of the catfish, a single fish/mouse chimeric Ig H gene is capable of
      producing IgM with a comparable amount of structural heterogeneity within the
      mouse cell. Thus, the piscine B lymphocyte routinely assembles a variety of redox
      forms from one IgM chain. This has both profound biosynthetic implications for
      macromolecular assembly processes as well as intriguing possibilities for the
      generation of teleost Ig functional diversity.

PMID- 9914907
TI  - The immunoglobulin light chain in poikilothermic vertebrates.
AB  - The immunoglobulin light chains are classified as kappa or lambda in mammals and
      birds (homeothermic vertebrates), but the traditional criteria for this
      classification are not applicable to the light chains found in poikilothermic
      vertebrates. Still it is possible to find some relationships between Ig light
      chain sequences in these animals and in those of the homeothermic animals. It is
      generally accepted that the Ig light chains contribute to the antigen binding
      capacity of antibodies and the variability is approximately similar in all
      studied vertebrate species except the elasmobranchs. This might be explained by
      the organisation of the Ig light chain locus in these animals and the fact that
      the variable and joining DNA segments are joined in the genome. These conclusions
      are limited by the small number of species studied in this respect.

PMID- 9914909
TI  - Evolutionary variation of immunoglobulin mu heavy chain RNA processing pathways:
      origins, effects, and implications.
AB  - Immunoglobulins (Ig) can occur in two physical forms, soluble (secreted) and
      membrane bound. The soluble form is secreted from B cells, and is present in the
      blood and other fluids where it plays a role as an immune effector molecule. The
      membrane-bound form of the Ig molecule is inserted into the B-cell membrane,
      where it serves as a receptor for antigen. The function of the membrane-bound Ig
      as a receptor for antigen requires additional accessory molecules, the membrane
      Ig plus accessory molecules are referred to, collectively, as the B-cell receptor
      (BCR) complex. The secreted and membrane-bound forms of an Ig result from
      alternative patterns of RNA processing of the primary transcript from the heavy
      chain gene. IgM is the only class of Ig known to be conserved in all vertebrate
      species (perhaps exclusive of the agnathan fish). While the structure of the IgM
      heavy (mu) chain gene has been highly conserved in vertebrate evolution, the
      patterns of alternative RNA processing of the mu transcript show surprising
      diversity. In particular, the bony fish (teleosts) produce membrane mu-chain
      message by a splicing pathway that is quite different from that seen in other
      vertebrates; it results in the production of membrane IgM that lacks the C mu 4
      domain. How this unusual RNA splicing pattern could have evolved and its
      implications for the function of the BCR in the bony fishes are considered here.

PMID- 9914910
TI  - The impact of ancestral tetraploidy on antibody heterogeneity in salmonid fishes.
AB  - The immunoglobulin heavy chain locus in teleost fish is structurally similar to
      that in mammals, comprising a series of variable gene segments upstream of two
      constant region genes coding for IgM and IgD. Atlantic salmon have been shown to
      possess two distinct heavy chain loci, related to the tetraploid ancestry of this
      fish family. The nature (and results) of the evolutionary processes following the
      tetraploidization event are the focus of this review. Salmonid fish did not
      return quickly to a diploid state, but are still in the process of re
      establishing disomic inheritance. Thus, a specific locus in one species may still
      be endowed with four alleles, while it may have been converted to a pair of
      isoloci in another species. Analyses of immunoglobulin heavy chain genes in
      Atlantic salmon (Salmo salar) have strongly indicated that the ancestral heavy
      chain locus was subjected to tetrasomy throughout the radiation of the genera
      Oncorhynchus and Salmo, and that disomic inheritance was established in the Salmo
      lineage in the comparatively recent past. The introduction of disomic inheritance
      at these loci has resulted in two subsets of IgM and IgD heavy chains in Atlantic
      salmon.

PMID- 9914911
TI  - What do the paralogous regions in the genome tell us about the origin of the
      adaptive immune system?
AB  - During the last decade, our understanding of the immune system of ectothermic
      vertebrates has advanced significantly. It is now clear that all jawed
      vertebrates are equipped with the adaptive immune system characterized by the MHC
      molecules and the rearranging receptors. In contrast, there is no molecular
      evidence that suggests the existence of adaptive immunity in jawless vertebrates.
      How did the adaptive immune system emerge? Our recent work suggests that one of
      the driving forces that enabled the emergence of the adaptive immune system was
      one or more genome-wide or large-scale chromosomal duplications presumed to have
      taken place in a common ancestor of jawed vertebrates.

PMID- 9914912
TI  - What brought the adaptive immune system to vertebrates?--The jaw hypothesis and
      the seahorse.
AB  - A hypothesis is discussed that the adaptive immune system of vertebrates evolved
      in the gastrointestinal regions of primitive jawed fish (placoderms) due to
      increased localized injuries and infections which were inadvertently brought
      about by the novel jaw structures and the predatory life style. The question
      whether the modern jawless fish, cyclostomes, have adaptive immunity or not is
      briefly but critically reviewed. The discovery that the gut-associated immune
      tissues in mammals constitute the primary immune tissues for the local T cells
      and that some epithelial gamma delta T cells have a unique propensity is
      summarized and discussed in relation to the jaw hypothesis. Initial study of the
      seahorse (Hippocampus) indicates that the gut-associated immune tissues may be
      absent in this teleost species, suggesting an evolutionary link between the
      adaptive immune system and the jaw structure or eating habit.

PMID- 9914913
TI  - Functional and molecular characterization of teleost leukocytes.
AB  - The coupling of immunologically relevant in vitro assay systems, cell separation
      techniques, and the development of distinct clonal leukocyte lines has
      established the existence of T, B, natural killer, and accessory cell equivalents
      in teleosts. B cells are directly defined by monoclonal antibodies to teleost
      immunoglobulin (Ig) and identification of Ig H and L chain genes. As in mammals,
      fish B cells show Ig H-chain gene rearrangements, allelic exclusion, produce both
      membrane-bound and secreted forms of Ig, and transduce intracellular
      proliferative signals upon anti-Ig cross-linking. It has also been found that
      some fish B cells express a unique chimeric Ig chain with sequence homology to
      mammalian Ig delta. Teleost T cells are still indirectly defined as sIg-
      lymphocytes due to a lack of definitive surface markers. These mIg- lymphocytes
      are the responding cells in mixed leukocyte cultures, proliferate specifically to
      autologously processed and presented antigen, provide helper function for in
      vitro antibody responses, and produce interleukin-like factors upon activation.
      Recent identification of teleost T-cell receptor alpha and beta genes has now
      permitted the unequivocal genetic demonstration that some of these mIg- cells are
      bona fide T cells. It is anticipated that such long-term clonal cell lines will
      be indispensable tools for dissecting the physiology, biochemistry and molecular
      biology of teleost immune responses.

PMID- 9914914
TI  - Lymphocyte development in fish and amphibians.
AB  - Recently, molecular markers such as recombination activating genes (RAG),
      terminal deoxynucleotidyl transferase (TdT), stem cell leukemia hematopoietic
      transcription factor (SCL), Ikaros and gata-binding protein (Gata)-family members
      have been isolated and characterized from key lower vertebrates, adding to our
      growing knowledge of lymphopoiesis in ectotherms. In all gnathostomes there
      appear to be two main embryonic locations derived from the early mesoderm, both
      intra- and extraembryonic, which contribute to primitive and definitive
      hematopoiesis based upon their differential expression of SCL, Gata-1, Gata-2 and
      myeloblastosis oncogene (c-myb). In teleosts, a unique intraembryonic location
      for hematopoietic stem cells termed the intermediate cell mass (ICM) of Oellacher
      appears to be responsible for primitive or definitive hematopoiesis depending
      upon the species being investigated. In Xenopus, elegant grafting studies in
      combination with specific molecular markers has led to a better definition of the
      roles that ventral blood islands and dorsal lateral plate play in amphibian
      hematopoiesis, that of primitive and definitive lymphopoiesis. After the early
      embryonic contribution to hematopoiesis, specialized tissues must assume the role
      of providing the proper microenvironment for T and B-lymphocyte development from
      progenitor stem cells. In all gnathostomes, the thymus is the major site for T
      cell maturation as evidenced by strong expression of developmental markers such
      as Ikaros, Rag and TdT plus expression of T-cell specific markers such as T-cell
      receptor beta and lck. In this respect, several zebrafish mutants have provided
      new insights on the development of the thymopoietic environment. On the other
      hand, the sites for B-cell lymphopoiesis are less clear among the lower
      vertebrates. In elasmobranchs, the spleen, Leydig's organ and the spiral valve
      may all contribute to B-cell development, although pre-B cells have yet to be
      fully addressed in fish. In teleosts, the kidney is undeniably the major source
      of B-cell development based upon functional, cellular and molecular indices.
      Amphibians appear to use several different sites (spleen, bone marrow and/or
      kidney) depending upon the species in question.

PMID- 9914915
TI  - Metamorphosis and the amphibian immune system.
AB  - Studies of the ontogeny of immunity in a limited number of representative
      amphibians have shown that while the immune systems of the larval forms are
      competent to defend against potential pathogens in the temporary ponds they
      inhabit, they are not equivalent to the mature immune systems that develop after
      metamorphosis. Metamorphosis is a critical time of transition when increased
      concentrations of metamorphic hormones, principally thyroid hormones (TH) and
      corticosteroid hormones (CH), orchestrate the loss or reorganization of many
      tissues and organ systems, including the immune system. Immune system
      reorganization may serve to eliminate unnecessary lymphocytes that could be
      destructive if they recognized newly emerging adult-specific antigens on the
      adult tissues. Increased corticosteroids during metamorphosis appear to induce
      apoptosis of susceptible lymphocytes. This cell death can be inhibited in vitro
      or in vivo by the corticosteroid receptor antagonist, RU486. A coordinate
      increase in both TH and CH at metamorphosis may be common to all amphibians that
      undergo metamorphosis. Current evidence suggests that the central hypothalamic
      mediator that induces pituitary production of both thyroid-stimulating hormone
      and adrenocorticotropic hormone in larval amphibians is corticotropin-releasing
      hormone. Most amphibians probably survive the temporary immunosuppression
      associated with metamorphosis with no deleterious effects. However, it is
      hypothesized that if environmental stressors result in the induction of
      metamorphosis at a less than optimal body size and state of immune maturation,
      the immune system destruction would be more significant, and the amphibians could
      be at greater risk of infection and death.

PMID- 9914916
TI  - Evolution of immune surveillance and tumor immunity: studies in Xenopus.
AB  - We have developed a novel experimental model of cancer immunity in the frog,
      Xenopus, which may provide a useful alternative to murine tumor models and a way
      to assess whether the control of tumor development is a fundamental function of
      the immune system of vertebrates. In Xenopus, tumor immunity can be studied in
      two developmentally distinct immune systems. The larval immune system reflects
      characteristics of an ancestral system that appears to function without classical
      MHC class I antigen presentation and an efficient effector mechanism. The adult
      system appears more highly evolved in that it is remarkably similar to that of
      mammals and is able to generate a potent antitumor response. This amphibian model
      also provides a unique system with which to investigate a postulated role of heat
      shock proteins as components of an ancestral system of antigen presentation
      and/or immune surveillance that predates the antigen presentation pathway that
      exclusively involves MHC molecules.

PMID- 9914917
TI  - T-cell and natural killer cell development in thymectomized Xenopus.
AB  - The Xenopus early-thymectomy model system is used to investigate the extent to
      which the thymus controls T-cell development and to probe the evolution of
      natural killer (NK) cells. Loss of T-cell function following thymectomy, together
      with the paucity of cells expressing monoclonal antibody-defined T-cell surface
      markers, and greatly reduced expression of T-cell receptor beta transcripts in
      spleen, liver and intestine, indicate that T-cell development in minimal in the
      absence of the thymus. Our findings therefore mitigate against the idea that a
      substantial extrathymic pathway of T-cell development exists in early vertebrate
      evolution. Rather, they suggest that in this amphibian representative T cells are
      predominately thymus dependent. In vitro studies with control and thymectomized
      Xenopus splenocytes reveal that a non-T/non-B population and also two T-cell
      subsets all display natural cytotoxicity towards allogeneic thymus lymphoid
      tumour cells (which are deficient in MHC antigen expression). Since Xenopus
      thymectomized early in larval development are permanently deficient in T cells,
      they may provide a useful phylogenetic model for the study of NK cells.

PMID- 9914918
TI  - Structure of MHC class I and class II cDNAs and possible immunodeficiency linked
      to class II expression in the Mexican axolotl.
AB  - Despite the fact that the axolotl (Ambystoma spp. a urodele amphibian) displays a
      large T-cell repertoire and a reasonable B-cell repertoire, its humoral immune
      response is slow (60 days), non-anamnestic, with a unique IgM class. The
      cytotoxic immune response is slow as well (21 days) with poor mixed lymphocyte
      reaction stimulation. Therefore, this amphibian can be considered as
      immunodeficient. The reason for this subdued immune response could be an altered
      antigenic presentation by major histocompatibility complex (MHC) molecules. This
      article summarizes our work on axolotl MHC genes. Class I genes have been
      characterized and the cDNA sequences show a good conservation of non-polymorphic
      peptide binding positions of the alpha chain as well as a high diversity of the
      variable amino acids positions, suggesting that axolotl class I molecules can
      present numerous antigenic epitopes. Moreover, class I genes are ubiquitously
      transcribed at the time of hatching. These class I genes also present an
      important polylocism and belong to the same linkage group as the class II B gene;
      they can be reasonably considered as classical class Ia genes. However, only one
      class II B gene has been characterized so far by Southern blot analysis. As in
      higher vertebrates, this gene is transcribed in lymphoid organs when they start
      to be functional. The sequence analysis shows that the peptide binding region of
      this class II beta chain is relatively well conserved, but most of all does not
      present any variability in the beta 1 domain in inbred as well as in wild
      axolotls, presuming a limited antigenic presentation of few antigenic epitopes.
      The immunodeficiency of the axolotl could then be explained by an altered class
      II presentation of antigenic peptides, putting into question the existence of
      cellular co-operation in this lower vertebrate. It will be interesting to analyze
      the situation in other urodele species and to determine whether our observations
      in axolotl represent a normal feature in urodele amphibians. But already two
      different models in amphibians, Xenopus and axolotl, must be considered in our
      search for understanding immune system and MHC evolution.

PMID- 9914919
TI  - The salmonid class I MHC: limited diversity in a primitive teleost.
AB  - Three MHC class I genes have been characterized in salmonids: A, B, and UA.
      Levels of polymorphism vary among the genes, but they all share one common
      feature: a lack of sequence diversity. Although individual species can carry over
      30 alleles at a given locus (A), intraspecific diversity is generally less than
      5% in Pacific salmon (genus Oncorhynchus), and less than 10% in Atlantic salmon
      (genus Salmo). These levels of diversity suggest that few ancient allelic
      lineages have persisted within species, and that most of the allelic radiation
      has occurred during or since speciation. Also apparent is the greater retention
      of allelic lineages in Atlantic salmon than Pacific salmon, which reflects
      historic differences of the two genera. Comparison of the salmonid class I
      sequences with those of other teleosts reveals two well supported groups: one
      containing the Cypriniformes and the salmonid UA, and the other containing the
      neoteleosts and the salmonid A and B. There is no homology between known
      Cypriniformes and neoteleostean sequences. If this relationship is borne out, it
      offers strong support for the hypothesis that the higher teleosts diverged more
      recently from the Salmoniformes than the Cypriniformes. The salmonid MHC may
      provide a snapshot of the neoteleostean MHC prior to the extensive class I
      duplication that has taken place in at least some of the more advanced species.

PMID- 9914920
TI  - Expressed major histocompatibility complex class II loci in fishes.
AB  - Peptides derived from parasites are presented to T helper cells by major
      histocompatibility complex (MHC) class II alpha beta heterodimeric cell-surface
      molecules. In mice and humans, the genes encoding these antigen-presenting
      molecules are known to be polymorphic and polygenic. Multiple loci for MHC class
      II A and B genes are proposed to allow for an increased peptide-binding
      repertoire. The multigenic nature of expressed MHC class II loci and the
      differences between these loci in fishes are the focus of this review. Particular
      emphasis is placed on an evolutionary comparison of class II B loci, especially
      two class II B loci that have undergone dramatic changes from one another
      suggesting an ancestral gene duplication event that took place at an early stage
      in the evolution of teleosts. The number of functional class II alpha beta
      heterodimers may have a profound impact on the organisms ability to battle
      constantly evolving parasitic infections.

PMID- 9914921
TI  - Major histocompatibility genes in cyprinid fishes: theory and practice.
AB  - The first teleostean MHC sequences were described for carp. Subsequent studies in
      a number of cyprinid fishes showed that the class I sequences of these fishes are
      of particular interest. Two distinct lineages (Cyca-Z and Cyca-U) are found in
      the common and ginbuna crucian carp, but only the U lineage is present in
      zebrafish and other non-cyprinid species. The presence of the Z lineage is
      hypothesised to be the result of an allotetraploidisation event. Both
      phylogenetic analyses and amino acid sequence comparisons suggest that Cyca-Z
      sequences are non-classical class I sequences, probably similar to CD1. The
      comprehensive phylogenetic analyses of these sequences revealed different
      phylogenetic histories of the exons encoding the extracellular domains. The MHC
      genes were studied in laboratory and natural models. The natural model addressed
      the evolution of MHC genes in a Barbus species flock. Sequence analysis of class
      I and class II supported the species designation of the morphotypes present in
      the lake, and as a consequence the trans-species hypothesis of MHC polymorphism.
      The laboratory model involves the generation of gynogenetic clones, which can be
      divergently selected for traits such as high and low antibody response. The role
      of MHC molecules can be investigated further by producing a panel of isogenic
      lines.

PMID- 9914922
TI  - What sharks can tell us about the evolution of MHC genes.
AB  - Similarity in structural features would argue that sharks possess class I, class
      IIA and class IIB genes, coding for classical peptide-presenting molecules, as
      well as non-classical class I genes. Some aspects of shark major
      histocompatibility complex genes are similar to teleost genes and others are
      similar to tetrapod genes. Shark class I genes form a monophyletic group, as also
      seen for tetrapods, but the classical and nonclassical genes form two orthologous
      clades, as seen for teleosts. Teleost class I genes arose independently at least
      four different times with the nonclassical genes of ray-finned fishes and all the
      shark and lobe-finned fish class I genes forming 1 clade. The ray-finned fish
      classical class I genes arose separately. In phylogenetic trees of class II alpha
      2 and beta 2 domains, the shark and tetrapod genes cluster more closely than the
      teleost genes and, unlike the teleost sequences, the class II alpha 1 domains of
      sharks and tetrapods lack cysteines. On the other hand, both shark and teleost
      genes display sequence motifs in the antigen-binding cleft that have persisted
      over very long time periods. The similarities may reflect common selective
      pressures on species in aqueous environments while differences may be due to
      different evolutionary rates.

PMID- 9914923
TI  - Rainbow trout cytokine and cytokine receptor genes.
AB  - Transforming growth factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta)
      have been cloned from rainbow trout (Oncorhynchus mykiss) in our laboratory. The
      trout TGF-beta is typical of members of the cysteine knot cytokine family, and
      has highest homology to TGF-beta 1, TGF-beta 4 and TGF-beta 5. The gene
      organisation is different to other TGF-beta genes despite the presence of seven
      exons. Trout IL-1 beta has less homology to known IL-1 beta s (49-56% amino acid
      similarity) but shows clear conservation of the secondary structure of the
      "mature peptide". An interleukin-converting enzyme cut site is not apparent
      however, and it remains to be determined whether fish IL-1 beta must be cleaved
      for biological activity. The trout IL-1 beta gene consists of six exons, one less
      than in mammals, with the missing exon at the 5' end of the gene. Two trout
      chemokine receptors have also been isolated in our laboratory, having high
      homology to CXC-R4 and CC-R7 (67% and 56% nucleotide identity respectively). With
      a view to studying the biological effects of fish cytokines we have also cloned
      the inducible nitric oxide (iNOS) and cyclooxygenase (COX-2) genes in trout. Both
      have high homology to known mammalian and chicken genes, and have been shown to
      be inducible in trout.

PMID- 9914924
TI  - CK-1, a putative chemokine of rainbow trout (Oncorhynchus mykiss).
AB  - Chemokines are small inducible proteins that direct the migration of leukocytes.
      While chemokines are well characterised in mammals, they have yet to be
      identified in fish. We have isolated a cDNA clone from rainbow trout
      (Oncorhynchus mykiss) which encodes a protein (CK-1) having structural features
      typical of chemokines. Amino-acid residues that define the beta-chemokines of
      mammals are conserved in CK-1, including the paired cysteine motif, CC. Further
      similarities are shared with the C6 subfamily of beta-chemokines. In contrast,
      the organisation of the CK-1 gene is closer to that of mammalian alpha-chemokine
      genes than beta-chemokine genes. The CK-1 gene is present in all four salmonid
      species examined and the nucleotide sequences of the exons are highly conserved.
      CK-1 has characteristics in common with mammalian alpha and beta-chemokine genes,
      suggesting that this salmonid chemokine gene preserves traits once present in the
      ancestral chemokine gene from which modern mammalian chemokine genes evolved.

PMID- 9914925
TI  - Interferon-inducible Mx proteins in fish.
AB  - Mx proteins are members of a family of interferon-inducible genes expressed when
      cells are treated with double-stranded RNA or virus infection. These proteins are
      important components of the antiviral response and form the first line of the
      body's defense against virus infections. The exact mechanism of action for these
      proteins has not been discovered, but mice missing the Mx genes are extremely
      sensitive to influenza virus infection. Mammals have between two and three Mx
      genes whose functions may vary with regard to the inhibition of a specific virus,
      cellular localization, and activity. The cDNA of three rainbow trout Mx proteins
      has been cloned and a comparison of their sequences with that of avian and
      mammalian species reveals striking conservation of domains. They all maintain the
      tripartite ATP/GTP binding domain and the dynamin family signature in the amino
      terminal half of the protein. In the carboxyl terminal half of the Mx proteins
      are the localization signals and the leucine zipper motifs which account for the
      trimerization of Mx in the cell. Like the rat and human Mx proteins, the
      different trout Mx proteins exhibit distinctly different immunohistochemical
      staining patterns in cells transfected with plasmids expressing RBTMx1, RBTMx2,
      or RBTMx3. To date, the antiviral function of the trout Mx proteins has not been
      satisfactorily established.

PMID- 9914926
TI  - Whirling disease: re-emergence among wild trout.
AB  - Whirling disease of rainbow trout is caused by Myxobolus cerebralis, a myxozoan
      parasite possessing a life cycle well adapted to the natural environments where
      salmonid fish are found. Whirling disease was first described in Europe in 1898
      among farmed rainbow trout but recent occurrences have been devastating to wild
      trout in North America. The disease is considered a major threat to survival of
      wild rainbow trout in the intermountain west of the United States. Difficulties
      in containing the spread and potentially eliminating the pathogen are tied to
      features of a complex life cycle involving two hosts, the salmonid fish and an
      aquatic oligochaete. Details of the morphologic development of the parasite have
      been described in each host but only now are we beginning to appreciate the
      breadth of interactions between these developmental forms and the sequential
      responses of the host. Fundamental mechanisms of the recognition and attachment
      of the parasite to the hosts, how host immunity is evaded and the unknown
      influences of environmental factors all contribute to a rather poor understanding
      of the biology of the parasite. Although the biology and ecology of the salmonid
      host are better known than for the oligochaete host, our knowledge is inadequate
      to interpret their complex interactions with the parasite. This uncertainty
      precludes the development of effective management activities designed to enhance
      the viability and productivity of wild trout populations in M. cerebralis
      positive river systems. Improving our understanding of the hosts, the parasite
      and the environmental factors determining their interaction should provide for
      more focused and effective control methods for containing the spread and
      devastating effects whirling disease is causing to our wild trout populations.

PMID- 9914927
TI  - Ichthyophthirius multifiliis: a model of cutaneous infection and immunity in
      fishes.
AB  - The parasitic ciliate Ichthyophthirius multifiliis offers a useful system for the
      study of cutaneous immunity against an infectious microorganism. Naive fish
      usually die following infection, but animals surviving sublethal parasite
      exposure become resistant to subsequent challenge. This resistance correlates
      with the presence of humoral antibodies in the sera and cutaneous mucus of immune
      fish. A mechanism of immunity has recently been elucidated that involves antibody
      binding to surface proteins (referred to as immobilization antigens or i
      antigens) located on the parasite cell and ciliary membranes. Antibody-mediated
      cross-linking of i-antigens triggers a response by the parasite resulting in its
      exit from the host. These effects can be observed directly on the surface of live
      fish. In addition to allowing the observation of effector responses in vivo,
      Ichthyophthirius also provides a means to study the ontogeny of the mucosal
      immune response. The sites of antigen capture and presentation, and the sites of
      antibody production, are unknown with regard to cutaneous immunity. Because the
      external epithelial surfaces of fish are often the points of pathogen entry, a
      basic understanding of the inductive immune mechanisms and immune cell
      interactions in the skin and gills is extremely important with regard to vaccine
      development. The development of Ichthyophthirius as an experimental system and
      how it might be used to address these issues are discussed in this review.

PMID- 9914928
TI  - Osteochondral resurfacing of the knee joint with allograft. Clinical analysis of
      33 cases.
AB  - This retrospective clinical study describes three years of experience with
      cryoprotected-cryopreserved allograft transplantation. During this period 33 knee
      joints were operated on for different reasons including osteoarthritis,
      osteochondritis dissecans and post-traumatic surface irregularity. The mean
      follow-up was nearly two years and the mean age of the patients was 48 years. The
      grafts were harvested and processed at the West Hungarian Tissue Bank according
      to the criteria promulgated by the European Association of Tissue Banks. All the
      operations were performed in the same way. Three types of grafts were used:
      cylindrical or mushroom-shaped for the femoral condyle and patellar and shell
      allografts for resurfacing the tibial plateau. Bone matrix gelatine (BMG) and
      fibrin sealant (Tissucol) were used locally to enhance the revascularisation and
      to improve the decreased osteoinductivity of the frozen cancellous bone.
      According to the modified Bentley score, the success rate of the short term
      follow-up was similar to that of other reported series. An analysis of four
      biopsies showed that the BMG and fibrin sealant did not appear to affect the
      viability of the articular cartilage. We conclude that application of these
      materials is not contra-indicated in allograft surgery.

PMID- 9914929
TI  - The rotational angle in osteoarthritic knees.
AB  - The angle of rotation of the knee joint during weight-bearing in osteoarthritic
      knees has not been fully determined. The authors aimed to examine the nature and
      extent of rotation during weight-bearing by means of ultrasonic investigation.
      There was a highly significant correlation between the rotational angle measured
      by ultrasound and that determined by CT. The dynamic rotatory movement during
      weight-bearing was measured in 107 osteoarthritic and 40 control knees. At 20
      degrees of flexion the internal rotation of the early grade I osteoarthritic
      knees (-1.6 degrees) was significantly less than that of the control knees (-4.8
      degrees, P = 0.004). This abnormality was the initial pathological rotational
      change in osteoarthritis of the knee joint. The external rotation at maximal
      extension and the rotation of the screw-home movement proportionately decreased
      with progression of medial compartment osteoarthritis. By virtue of these
      observations we have clarified the dynamic rotatory movement in osteoarthritic
      knees during weight-bearing.

PMID- 9914930
TI  - Anterior cruciate ligament reconstruction: the diagnostic value of MRI.
AB  - A prospective study was carried out in order to evaluate the predictive value of
      MRI in the early postoperative course after cruciate ligament replacement. Twenty
      patients who had undergone anterior cruciate ligament reconstruction using
      autologous patellar tendon/bone grafts were examined clinically and with contrast
      enhanced MRI at 2, 12 and 24 weeks, and 1 and 2 years after operation. The
      clinical findings were evaluated according to the scores established by Lysholm,
      OAK and IKDC. The MRI scans (SP 63, 1.5 Tesla) were assessed in terms of the
      quality and signal intensity of the reconstructed ligaments. During the first
      postoperative year there was a significant increase of signal intensity and in
      homogeneity of the neoligament on in the MRI. Seventeen patients had an average
      value for signal/noise of 1.1 at two weeks after surgery, which had increased to
      7.1 at 1 year. In 14 patients the reconstructed ligament could not be evaluated
      in MRI scans after 1 year but clinical instability was not suspected in any of
      these patients. Two years after operation the MRI signal, intensity of the
      neoligament was again decreasing.

PMID- 9914931
TI  - Tibial bone defects treated by internal bone transport using the Ilizarov method.
AB  - We reviewed 27 cases of tibial bone defects treated by internal bone transport
      using the Ilizarov method. The causes of the bone defects were open fractures in
      14 segments and infected non-unions in 13. The average length of the defects was
      8.3 cm (range, 3-20 cm). There were 21 one-level tibial transports, 3 two-level
      tibial transports, 1 one-level tibial transport with fibular transport, and 2
      fibular transports. At the docking site, 25 segments underwent bone grafting.
      Eleven of the 25 were Papineau-type open cancellous bone grafts. Acute shortening
      or docking was performed in 10 segments. Bone union was obtained in every
      instance. The average time of external fixation was 8 months and the average time
      to union was 7.1 months. Bone grafting at the docking site is recommended in
      order to shorten the duration of treatment and to prevent refracture and non
      union.

PMID- 9914932
TI  - The treatment of infected non-union of the tibia by compression-distraction
      techniques using the Ilizarov external fixator.
AB  - Circular external fixation using the Ilizarov apparatus combined with compression
      distraction techniques was used to treat 11 patients with infected non-union and
      segmental bone loss of the tibia. The series comprised 8 males and 3 females,
      with an average age of 27 years (range 17-51 years). The average number of
      previous failed surgical attempts at union was 2 per patient (range 1 to 4).
      Three infected non-unions without shortening were treated with complete resection
      of the site and conversion of the diaphysis into a segmental defect. The
      functional results were excellent in 5, good in 3, fair in 2 and poor in one
      patient. No additional procedures were used in any of the patients.

PMID- 9914933
TI  - Audit of autotransfusion in spine surgery.
AB  - A prospective evaluation has been undertaken of 382 patients undergoing
      reconstructive spine surgery during a thirty-six month period. Acute
      normovolaemic haemodilution and haemapheresis for blood component sequestration
      was used in 80 patients in the operating theatre. An average of two units each of
      freshly collected autologous red cells and fresh plasma together with a
      therapeutic dose of a plateletpheresis product were prepared for each patient
      prior to surgical incision. The same supplies and equipment were subsequently
      used for conventional blood salvage and autotransfusion. The other 302 patients
      received salvaged blood only. Of the total blood transfused, autologous red cells
      comprised 87% of sequestration and 49% of autotransfusion-only patients. Each
      group received the same total perioperative red blood cell support. The cost for
      one red cell equivalent by intraoperative autologous transfusion was competitive
      with that of providing one unit of cross-matched allogeneic red cells. As
      compared with salvage alone, sequestration combined with salvage was even more
      cost effective and decreased reliance on allogenic products and preoperative
      autologous blood donations. The rate of transfusing autologous blood products was
      markedly increased.

PMID- 9914934
TI  - Femoral cementing techniques in total hip replacement.
AB  - Clinical studies have shown that second-generation femoral cementing techniques
      at total hip replacement result in a superior fixation of the femoral stem. In an
      effort to determine what benefits further developments in cementing techniques
      would provide, we compared the morphology of the cement mantles produced by
      traditional finger-packing and gun-insertion techniques. The porosity of the
      cement mantles was quantified using computerised image analysis. The finger
      packing technique caused large air inclusions that resulted in large pores in the
      substance of the cement mantle, whereas the cement-gun technique did not result
      in any individual pore with an equivalent diameter greater than 3 mm. The mean
      porosity of cement mantles prepared using the finger-insertion technique was
      8.3%, whereas the mean porosity in gun-prepared mantles was 1.7%. The use of a
      cement gun significantly reduced the porosity of femoral cement mantles (P =
      0.02). Reduction of defects in the substance of the cement mantle may account for
      the increased survival of femoral prostheses inserted when second-generation
      techniques were used. Further reduction of the porosity of the cement mantle
      could not be expected to produce as dramatic a clinical improvement in prosthesis
      fixation.

PMID- 9914935
TI  - Use of the suture anchor in modified open Bankart reconstruction.
AB  - This study describes the 2-year follow-up of Bankart reconstruction in 44
      patients with posttraumatic recurrent anterior instability of the shoulder, using
      suture anchors and reinforcing the repair with a subscapularis overlap. Forty
      three of 44 patients (98%) regained normal stability. One recurrent dislocation
      occurred. The mean loss of external rotation was 15 degrees. The functional
      results according to the Rowe scoring system were excellent in 30 cases, good in
      13 cases, and poor in 1 case. The suture anchors were found to simplify the
      procedure.

PMID- 9914936
TI  - Non-operative treatment versus tension-band osteosynthesis in three- and four
      part proximal humeral fractures. A retrospective study of 34 fractures from two
      different trauma centers.
AB  - Thirty-four patients with three- and four-part proximal humeral fractures from
      two different trauma centres were studied retrospectively. Sixteen were treated
      without osteosynthesis and compared with 18 patients treated with tension-band
      fixation. Fracture classification and clinical examination were made by the same
      persons in both groups. Most of the three-part fractures healed with good pain
      relief and good function in daily life but often with a loss of motion. Four-part
      fractures often led to pain, loss of motion and of function. Conservative
      treatment seemed superior to tension-band fixation for three-part fractures. Four
      part fractures healed with better function and range of motion after tension-band
      fixation.

PMID- 9914937
TI  - Immediate ipsilateral fibular transfer in a large tibial defect using a ring
      fixator. A case report.
AB  - Massive segmental bony defects in open tibial fractures are generally treated
      with conventional bone grafting, a free vascularised fibular graft or the ring
      fixator technique. A vascularised fibular graft may be superior to a conventional
      bone graft, but it is technically difficult and occasionally impossible. In such
      circumstances, fibular transfer in conjunction with a ring fixator is an
      alternative method. This procedure can be accomplished by transferring the
      osteotomised part of the fibula to the tibia by means of olive wires. The authors
      have treated a 20-year-old male who presented with a Gustilo type IIIB open
      tibial fracture. The soft tissue defect was severe, only the tibialis posterior
      artery was patent and the peroneal artery was partially damaged. A latissimus
      dorsi flap was performed to cover the soft tissue defect. Since the patent
      tibialis posterior artery had already been used for the flap, it was difficult to
      perform a vascularised fibular graft. Moreover, it was technically difficult to
      accomplish a gradual transport using a ring fixator because the distal tibia was
      lost. For this reason, the fibular transfer was performed immediately after the
      ring fixator was applied. Good bony union and fibular hypertrophy were obtained
      even though these two procedures were undertaken simultaneously.

PMID- 9914938
TI  - Large synovial cyst of the pelvis containing rice bodies. A case report.
AB  - Although synovial pelvic cysts are very uncommon they enter into the differential
      diagnosis of presacral and ovarian cysts. In the elderly male whom we report, a
      large cyst arose from the hip and extended during a five year period to involve
      the entire pelvic cavity. The cyst, which contained a large number of "rice
      bodies" was excised surgically.

PMID- 9914939
TI  - Intra-articular lipoma of the hip. A case report.
AB  - This report describes a rare intra-articular lipoma of the hip which developed in
      a 31-year-old male after a football injury. A plain X-ray and an MRI scan of the
      hip showed no bony abnormalities. After the patient failed to improve with a
      rehabilitation programme, arthroscopy of the hip was performed, revealing a lump
      in the acetabular fossa associated with a labral tear. A histopathological
      analysis confirmed the diagnosis of an intra-articular lipoma of the hip joint,
      which to our knowledge is the first reported case in the literature.

PMID- 9914940
TI  - Preservation of the knee joint in limb salvage of osteosarcoma in the proximal
      tibia. A case report.
AB  - A 12-year-old boy with osteosarcoma in the proximal tibia underwent a successful
      limb-saving operation with preservation of the epiphyseal and articular cartilage
      of the proximal tibia as a result of his remarkable response to chemotherapy.
      There was no evidence of tumour invasion to the adjacent physis, as demonstrated
      by image findings. The bone defect was reconstructed using autoclaved autogeneous
      bone with a vascularized fibula. The patient exhibits excellent function of the
      affected limb, and the knee joint remains disease-free 55 months postoperatively.

PMID- 9914941
TI  - Osteoinduction by demineralised bone.
AB  - Bone contains several growth factors, including bone morphogenetic proteins
      (BMPs), transforming growth factor beta (TGF-beta), insulin-like growth factors I
      and II (IGF-I and IGF-II), platelet derived growth factor (PDGF) and basic and
      acidic fibroblast growth factor (bFGF and aFGF). The BMPs are the only factors
      known to provoke bone formation heterotopically by making undifferentiated
      mesenchymal cells differentiate into osteoblasts (osteoinduction). Much of our
      knowledge of osteoinduction derives from studies in rodents of heterotopically
      implanted demineralised bone which contains various growth factors, including
      BMPs. This model has been used to examine the effect on osteoinduction of
      different factors, including the type of host soft tissue, age and species of
      donor and recipient, demineralisation procedure, storage and sterilisation
      procedures, experimental diabetes, dietary factors, hormones, growth factors,
      caffeine, biphosphonates, indomethacin and biomaterials. Demineralised bone
      enhances bone formation experimentally in various animal models, including cranio
      maxillofacial reconstructions, healing of diaphyseal defects, and spinal fusion;
      demineralised bone has also been used in a limited way clinically. However,
      sufficient osteoinduction in humans may require a higher concentration of BMPs
      and other growth factors than those found in demineralised bone.

PMID- 9914942
TI  - Interleukin-4 and interleukin-13: their similarities and discrepancies.
AB  - Interleukin-4 (IL-4) and the closely related cytokine, interleukin-13 (IL-13)
      share many biological and immunoregulatory functions on B lymphocytes, monocytes,
      dendritic cells and fibroblasts. Both IL-4 and IL-13 genes are located in the
      same vicinity on chromosome 5 and display identical major regulatory sequences in
      their respective promoters, thus explaining their restricted secretion pattern to
      activated T cells and mast cells. The IL-4 and IL-13 receptors are multimeric and
      share at least one common chain called IL-4R alpha. Recent progress made in the
      description of IL-4 and IL-13 receptor complex have demonstrated the existence of
      two types of IL-4 receptors: one constituted by the IL-4R alpha and the gamma c
      chain, and a second constituted by the IL-4 R alpha and the IL-13R alpha 1 and
      able to transduce both IL-4 and IL-13 signals. Specific IL-13 receptors are
      results from the association between the IL-4R alpha and the IL-13R alpha 2 or
      between two IL-13R alpha. Furthermore, similarities in IL-4 and IL-13 signal
      transduction have been also described, thus explaining the striking overlapping
      of IL-4- and IL-13-induced biological activities such as regulation of antibody
      production and inflammation. However, the restricted expression of IL-4 to type 2
      helper T lymphocytes as well as the inability of IL-13 to regulate T cell
      differentiation due to a lack of IL-13 receptors on T lymphocytes represent the
      major differences between these cytokines. This would indicate that although IL-4
      and IL-13 share a large number of properties, precise mechanisms of regulation
      are also present to guarantee their distinct functions.

PMID- 9914943
TI  - Type I interferons.
AB  - Type I interferons (IFNs) constitute a family of structurally related proteins
      that are all derived from the same ancestral gene and act on a common cell
      surface receptor. Contrary to many other cytokines, the production of type I IFNs
      is not a specialized function, and all cells in the organism can produce them,
      usually as a result of induction by viruses, via the formation of double-stranded
      RNA. Type I IFNs are indeed responsible for the first line of defense during
      virus infection and act through the induction of a great number of proteins. Of
      these, at least thirty have been characterized, and there are probably many more.
      In addition to their direct antiviral effect, type I IFNs exert a wide variety of
      other activities, such as for example the induction of various cytokines and the
      stimulation of different effector cells of the immune system. Due to these
      pleiotropic effects, recombinant interferons are used in the clinic to treat a
      variety of diseases, among which cancer, viral hepatitis and multiple sclerosis.

PMID- 9914944
TI  - Signal transduction through cytokine receptors.
AB  - Receptors for interleukins, colony stimulating factors, and hormones have a
      homology in their extracellular regions, characterized by the conserved cysteine
      residues and the tryptophan-serine-x-tryptophan-serine motif, thus, they are
      classified to the type 1 cytokine receptor superfamily. Janus tyrosine kinase
      (JAKs) have been found to be involved in the signal transduction through type I
      cytokine receptors. JAKs associate with the membrane proximal region in the
      cytoplasmic domain having box1 and box2, which are conserved among the family,
      and upon the stimulation JAKs can be aggregated following the receptor
      dimerization and activated probably by transphosphorylation. JAKs then
      phosphorylate the receptor and various signal transducing molecules, including
      STATs (signal transducer and activator of transcriptions) and other SH2
      containing adapter molecules. STATs were initially identified as transcription
      factors containing a SH2 domain and regulating interferons-inducible genes. STATs
      can be tyrosine phosphorylated by JAKs and form dimer (either hetero- or homo
      dimers) to enter the nucleus, resulting in the expression of a set of genes. On
      the other hand, adapter molecules such as Shc, GRB2, and SHP-2 have been shown to
      link the cytokine receptors to Ras, followed by the activation of the Raf-MEK-MAP
      kinase pathway, leading to the activation of various transcription factors in the
      nucleus. These two signals are generated by different ways upon the stimulation
      of the receptors and they elicit a variety of biological functions in various
      cell types. In this review, we will discuss the mechanism by which cytokines
      activate JAKs, STATs, and a variety of adapter molecules. We further discuss the
      roles of each signal transduction pathways in the expression of biological
      activities of cytokines.

PMID- 9914945
TI  - Inherited cytokine and cytokine receptor deficiencies in man.
AB  - Over the past decades, cytokines and their receptors have been shown to play a
      decisive role in the differentiation of both innate and adaptive immunity. The
      essential roles of cytokine/receptor pathways in vivo, however, have remained
      elusive and poorly defined. In some cases, primary immunodeficiency syndromes
      have provided the natural models in which the role of cytokines and their
      receptors in the development and function of the immune system have been
      elucidated. Animal models of cytokine/receptor deficiencies generated through
      gene targeting have also played a decisive factor in identifying the true
      biological roles of cytokine/receptor pathways. The end result of these
      approaches has been an enormous advance in our understanding of the cytokine
      control of normal and pathological human conditions, as well as the advent of new
      diagnostic tools and novel therapies.

PMID- 9914946
TI  - Subversion of cytokine networks by viruses.
AB  - Viruses and the immune system have been competitors throughout their co
      evolution. It is therefore not surprising that the viruses in circulation today
      possess a variety of strategies to counteract those aspects of the immune system
      that are involved in virus clearance. Examination of these virus encoded
      functions provides an important view of immune function and an appreciation of
      the complexity of the virus-host interaction. It is clear that viruses, seeking
      to subvert the immune system, have become adept in blocking the communication
      channels of the immune system. There are numerous examples of viral proteins that
      target the cytokine networks, disrupting the processes by which the delicately
      balanced immune system is regulated. This review focuses on the gene products of
      poxviruses, adenoviruses and herpesviruses that function primarily as immune
      modulators.

PMID- 9914947
TI  - Cytokines in parasitic diseases: the example of cutaneous leishmaniasis.
AB  - The essential role of cytokines in parasitic diseases has been emphasised since
      the in vivo description of the importance of T helper 1 (Th1) and T helper 2
      (Th2) CD4+ T cell responses in resistance and susceptibility to infection with L.
      major in mice. Th1 cells produced IL-2, IFN-gamma and Lymphotoxin T (LT) and Th2
      cells produce IL-4, IL-5 and IL-13. In this model of infection the correlation
      between on the one hand resistance to infection and the development of a Th1
      response and on the other hand susceptibility and Th2 cell development allowed
      the identification of the mechanisms directing the differentiation of CD4+ T cell
      precursors towards either Th1 type or Th2 type responses. Cytokines are the
      crucial inducer of functional CD4+ T cell subset differentiation during infection
      with L. major. IL-12 and IFN-gamma direct the differentiation of Th1 response and
      IL-4 of a Th2 response. In susceptible mice, careful analysis of IL-4 production
      during the first days of infection has shown that the IL-4 produced as a result
      of a very early burst of IL-4 mRNA expression (16 hours) plays a essential role
      in the maturation of a Th2 CD4+ T cell response by rendering the CD4+ T cell
      precursors unresponsive to IL-12. Activation of a restricted population of CD4+ T
      cells expressing the V beta 4 V alpha 8 TCR heterodimer after recognition of a
      single antigen, the LACK (Leishmania Activated c Kinase) antigen, resulted in
      this rapid production of IL-4 required for the subsequent CD4+ T cell
      differentiation. Thus, tolerization of these cells might contribute a strategy
      for preventing infection with L. major.

PMID- 9914948
TI  - Cytokines in the neuroendocrine system.
AB  - Cytokines are important partners in the bidirectional network interrelating the
      immune and the neuroendocrine systems. These substances and their specific
      receptors, initially thought to be exclusively present in the immune system, have
      recently been shown to be also expressed in the neuroendocrine system. Cytokines
      can modulate the responses of all endocrine axes by acting at both the central
      and the peripheral levels. To explain how systemic cytokines may gain access to
      the brain, several mechanisms have been proposed, including an active transport
      through the blood-brain barrier, a passage at the circumventricular organ level,
      as well as a neuronal pathway through the vagal nerve. The immune-neuroendocrine
      interactions are involved in numerous physiological and pathophysiological
      conditions and seem to play an important role to maintain homeostasis.

PMID- 9914949
TI  - Cytokines in autoimmune disorders.
AB  - Cytokines are important protein mediators of immunity, inflammation, cell
      proliferation, differentiation, fibrosis, etc. (Oppenheim and Saklatvala, 1993).
      As these are the major biological processes underlying autoimmunity, it is not
      surprising that there is now convincing evidence that cytokines have an important
      role in the pathogenesis of autoimmunity (Brennan and Feldmann, 1996; Feldmann et
      al., 1996). There has been much progress since we first highlighted the role of
      cytokines such as IFN gamma in autoimmunity in the early 1980s (Bottazzo et al.,
      1983). The number of cytokines molecularly cloned has increased greatly, and the
      biochemical and structural basis of their action are partly understood, as
      cytokine genes and that of their receptors have been cloned. Knowledge of
      cytokine signalling is rapidly expanding (see Chapter XIII). In medical terms,
      clear evidence of the importance of cytokines in autoimmunity is demonstrated by
      therapeutic advances. Thus it is possible to dramatically improve patients with
      rheumatoid arthritis and Crohn's disease by blocking TNF alpha, and a new target
      for therapy, TNF alpha, has thus been validated for both these diseases.

PMID- 9914951
TI  - [Three months intravenous repeated dose toxicity study of T-3762 in rats].
AB  - A three months intravenous repeated dose toxicity study of T-3762, a novel
      parenteral quinolone antibacterial agent, was carried out in rats at dose levels
      of 4, 13, 39, 130 mg/kg. Fifteen rats of each sex were used in each group. Out of
      these, 5 rats of each sex were used for the recovery study. The following results
      were obtained. 1. There were no death caused by T-3762 within the study period.
      In clinical signs, the squeaks during injection in 130 mg/kg group were observed,
      but they decreased day by day. In body weight changes, a tendency to very slight
      decrease of weight gain in male 130 mg/kg group were seen, but there was no
      significant difference from control group. In food and water consumption, there
      was no abnormality. 2. There were no abnormality caused by T-3762 in urinalysis,
      hematological examination and ophthalmological examination. 3. In blood chemistry
      examinations, increase of A/G ratio was seen in 13, 39 and 130 mg/kg groups, but
      it showed tendency of recovery after withdrawal period. 4. In macroscopic and
      histological findings, erosion and cavitation of the articular cartilage were
      seen in 3 of 20 rats in 130 mg/kg group and 1 of 20 rats in 39 mg/kg group. 5.
      Non-toxic dose levels is estimated to 13 mg/kg, that showed no abnormality in the
      articular cartilage in this study.

PMID- 9914950
TI  - [Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone
      antimicrobial agent, in rats, dogs and monkeys].
AB  - Single dose intravenous toxicity studies of T-3762, a novel parenteral quinolone
      antimicrobial agent, were conducted in rats, dogs and monkeys. The following
      results were obtained. 1. In the rat study, all males and females given 260 mg/kg
      survived and all males and 3 of 5 females given 391 mg/kg died. Approximate
      lethal doses in male and female rats were between 260 and 391 mg/kg. In survived
      animals, decrease in locomotor activity and irregular respiration were observed.
      These clinical signs were recovered within 1 hour after dosing. In female rats
      given 260 mg/kg, no abnormalities were observed in general signs. In dead
      animals, decrease in locomotor activity, irregular respiration, staggering gait
      and tonic convulsion were observed and died within about 90 minutes after dosing.
      Macroscopic examinations in dead animals showed dark red discoloration in lung
      and had white foamy liquid in trachea. In histopathological examinations of dead
      animals, congestion, hemorrhage and edema were observed in lung. 2. In the dog
      study, 2 animals given 260 mg/kg survived and 2 animals given 521 mg/kg died.
      Approximate lethal dose in dogs was between 260 and 521 mg/kg. In the 260 and 521
      mg/kg groups, decrease in locomotor activity, lateral position, vomiting,
      salivation and decrease in body temperature were observed. In the 521 mg/kg
      group, one animal died at 4 minutes and another 7 days after dosing.
      Histopathological examinations in 2 dead animals showed congestion or hemorrhage
      in heart, lung, liver, kidney, spleen and digestive tract. Erosion and necrosis
      at cartilage layer and cluster of chondrocyte were observed in scapular fossa and
      head of humerus in the 260 and 561 mg/kg groups. 3. In the monkey study, 2
      animals given 260 mg/kg survived and 2 animals given 520 mg/kg died. Approximate
      lethal dose in monkeys was between 260 and 520 mg/kg. In the 260 mg/kg group,
      soft feces was observed. In the 520 mg/kg group, paleness mucosa of oral cavity,
      muscle weakness, mydriasis and dyspnea were observed and animals died within 4
      minutes after dosing. Macroscopic and histopathological examinations in 2 dead
      animals showed congestion in lung, liver and kidney.

PMID- 9914952
TI  - [Elevated levels of plasma homocysteine related to saphenous vein graft disease
      after coronary artery bypass graft surgery].
AB  - Elevated levels of plasma homocysteine may be an independent risk factor for
      coronary atherosclerosis. This study investigated whether plasma homocysteine
      levels are related to atherosclerotic lesions of saphenous vein grafts after
      coronary artery bypass surgery. Homocysteine levels were measured in fasting
      plasma by high-performance liquid chromatography and total cholesterol,
      triglyceride, high density lipoprotein cholesterol and lipoprotein (a) were also
      evaluated in 40 patients (mean age 65 +/- 8 years, mean interval after bypass
      surgery: 6.1 +/- 3.1 years, range 1-13 years). The vein graft disease group was
      defined as patients with angiographical stenosis of > or = 50% in any vein graft
      (n = 23). The other patients were defined as the no-vein graft disease group (n =
      17). Patients who had a history of chronic renal failure or anatomic lesions of
      saphenous vein grafts were excluded. The distributions of homocysteine were
      skewed. Median homocysteine levels were 11.9 nmol/ml in all subjects.
      Homocysteine levels in the vein graft disease group were significantly higher
      than in the no-vein graft disease group (median 15.1 vs 10.6 nmol/ml, p = 0.01).
      In the analysis of plasma lipids, high-density lipoprotein cholesterol levels
      were significantly lower in the vein graft disease group than in the no-vein
      graft disease group (mean 37 +/- 11 vs 48 +/- 13 mg/dl, p = 0.01). Multiple
      regression analysis showed that elevated levels of homocysteine were an
      independent risk factor for saphenous vein graft disease after coronary artery
      bypass surgery. These findings indicate that elevated levels of plasma
      homocysteine are related to atherosclerotic lesions of saphenous vein grafts
      after coronary artery bypass surgery as well as coronary atherosclerosis.

PMID- 9914953
TI  - [Multiple overlapping Wiktor stenting for the treatment of diffuse lesions of
      small coronary arteries].
AB  - This study evaluated the usefulness of multiple overlapping stenting for the
      treatment of a diffuse lesion in a single and small coronary artery. We studied
      48 consecutive patients with a lesion of a vessel with reference diameter < 3.0
      mm who received Wiktor stent implants due to suboptimal result or threatened
      closure after plain old balloon angioplasty (POBA). The patients were divided
      into 2 groups: Group D, 18 patients with a diffuse lesion with length > or = 15.0
      mm who were treated with 2 overlapping Wiktor stents; and Group S, 30 patients
      with a discrete lesion who were treated with a single Wiktor stent. Two patients
      with a discrete lesion were not included in Group S because of failure of
      stenting. Stenting was successful in all patients in Group D. One patient in
      Group S developed subacute thrombosis after stenting. Follow-up angiography was
      performed after 6 months. Before treatment, the lesion lengths in Groups D and S
      were 24.2 +/- 10.0 and 9.2 +/- 4.4 mm, the reference diameters were 2.56 +/- 0.32
      and 2.69 +/- 0.33 mm, and the minimal lumen diameters were 0.42 +/- 0.34 and 0.53
      +/- 0.40 mm, respectively, with no significant difference in the latter 2
      parameters. Restenosis occurred in 72% and 30% (p = 0.01) and revascularization
      of the target lesion was successful in 67% and in 30% (p = 0.03), in Groups D and
      S, respectively, both significantly higher in Group D. Follow-up study revealed
      that the minimal lumen diameter and the net gain were significantly greater in
      the overlapping portion of the 2 stents than in the proximal and distal portions
      in Group D, with no significant difference in restenosis rate between these 3
      portions. Multiple overlapping stenting using Wiktor stents is useful for diffuse
      lesions with unfavorable results after POBA even if the affected vessel is
      smaller than 3.0 mm. However, patients should be carefully observed because
      restenosis occurs frequently.

PMID- 9914954
TI  - [Does left ventricular wall motion of akinetic segment improve after reperfusion
      therapy in patients with acute myocardial infarction?: assessment by myocardial
      contrast echocardiography].
AB  - The relationship between myocardial perfusion and left ventricular wall motion
      was studied by myocardial contrast echocardiography in 22 patients with acute
      myocardial infarction treated by successful direct percutaneous transluminal
      coronary angioplasty (PTCA). Myocardial contrast echocardiography was performed 4
      times to assess the serial changes of wall motion score and opacification score,
      before and immediately after PTCA, and 2 weeks and 3 months after the onset of
      infarction, by injecting 2 ml Albunex into the infarct-related artery. Two
      dimensional echocardiography was visualized at the level of the papillary muscle
      on the short-axis view or apical long-axis view. Wall motion score was graded
      visually as grade 0: dyskinesis/akinesis, to 3: normokinesis/hyperkinesis and
      opacification score was graded as grade 0: no opacification, to 2: homogeneous
      opacification using the 6-segment model of the short-axis view or 5-segment model
      of the apical long-axis view. Immediately after PTCA, we observed 30 segments
      with the dyskinesis/akinesis, which were divided into 3 groups (no opacification
      group, partial opacification group and homogeneous opacification group) by
      opacification score immediately after PTCA. The recovery of left ventricular wall
      motion in the partial opacification group (10 segments) and homogeneous
      opacification group (7 segments) were significantly better than the no
      opacification group (13 segments). Six (46%) of 13 segments in the no
      opacification group had improved contrast enhancement 3 months later, and 4 of
      these 6 segments showed improved left ventricular wall motion. The area opacified
      immediately after PTCA showed recovery of left ventricular wall motion in the
      chronic stage. However, some segments of the no-opacified area immediately after
      PTCA also showed improved myocardial opacification as well as improved left
      ventricular wall motion in the chronic stage. The results suggest that myocardial
      contrast echocardiography is an important method to predict myocardial viability,
      but it is difficult to assess the viability by contrast enhancement performed
      only in the acute stage of acute myocardial infarction.

PMID- 9914955
TI  - Intimal proliferation after stenting reflected by increased stent-to-vessel cross
      sectional area ratio: serial intravascular ultrasound study.
AB  - Minimizing the extent of neointimal proliferation helps to maintain the maximal
      vessel lumen after the treatment of stenosis. The present study examined factors
      influencing the predisposition to neointimal proliferation, which is a
      consequence of Palmaz-Schatz stenting. Serial intravascular ultrasound
      examinations of 32 lesions (4 lesions/patient) were performed after stenting and
      at 6 months follow-up in 8 non-restenotic patients. Vessel, lumen and stent cross
      sectional areas (CSA) were measured. Stent-to-vessel CSA ratio at stenting,
      changes of lumen CSA, vessel CSA and intima CSA (neointimal proliferation) were
      calculated. Six months after stenting, lumen CSA was reduced corresponding to an
      increase of intima without change of vessel CSA (without remodeling). Greater
      stent-to-vessel CSA at stenting was associated with higher neointimal
      proliferation at follow-up. The proliferative response was the same at all stent
      edges. Stent CSA was reduced as stent dilation was increased. The stent CSA
      became smaller but stent shrinkage did not account for late lumen loss. Late
      lumen loss in stents is the result of neointimal proliferation in cases without
      restenosis, and a larger stent-to-vessel CSA ratio reflects increased neointimal
      proliferation, as shown at 6-month follow-up.

PMID- 9914957
TI  - [Cardiac disorders associated with progressive systemic sclerosis].
AB  - This study investigated cardiac disorders in 25 patients with diagnoses of
      progressive systemic sclerosis based on the criteria of the American College of
      Rheumatology. All were women, and the mean age was 59 +/- 11 (range 41-80) years
      old. The duration of the disease was 11 +/- 9 (range 3-40) years. The following
      complications were seen; Raynaud's phenomenon in all, esophageal disorders in 11,
      pulmonary fibrosis in 9, diabetes mellitus in 3, high blood pressure in 6,
      hyperlipidemia in 7, and positive anticardiolipin antibody in 8.
      Electrocardiography (ECG) and echocardiography were performed to assess the
      cardiac disorders. Abnormal ECG was seen in 11 patients (44%) and abnormal
      echocardiograms in 16 patients (64%). ECG abnormalities included incomplete right
      bundle branch block in 8 (32%), low voltage in 3 (12%), supraventricular
      arrhythmia in 3 (12%), ventricular arrhythmia in 1 (4%) and septal myocardial
      infarction pattern in 1 (4%). Echocardiographic abnormalities included valvular
      diseases in 13 (52%) and pericardial thickening in 7 (28%). No relationship was
      found between ECG and echocardiographic abnormalities. Echocardiographic
      abnormalities were more frequently observed in patients with positive
      anticardiolipin antibody (7/8, 88%) than in those with negative anticardiolipin
      antibody (9/17, 53%). Especially, pericardial thickening was seen in 63% (5/8) of
      positive patients, in comparison to 12% (2/17) of the negative patients (p <
      0.05). Patients with progressive systemic sclerosis may have several cardiac
      disorders including conduction disturbances, low voltage ECG, valvular diseases
      and pericardial thickening. Pericardial thickening has a close relationship with
      positive anticardiolipin antibody.

PMID- 9914956
TI  - [Effectiveness of surgical repair of mitral regurgitation concomitant with
      dilated cardiomyopathy].
AB  - Dilated cardiomyopathy (DCM) is often accompanied by severe mitral regurgitation
      (MR) which deteriorates the clinical course. Mitral reconstruction for severe MR
      may improve the symptoms and prognosis. Five patients with DCM and one patient
      with dilated phase of hypertrophic cardiomyopathy underwent mitral reconstruction
      for severe MR (4 males, 2 females, mean age 50 +/- 17 years) from 1983 to 1995.
      Their New York Heart Association (NYHA) functional class and findings of
      echocardiography and cardiac catheterization were compared before and after
      surgery. Five patients underwent annuloplasty and one patient underwent
      mechanical valve replacement. There was no operative or in-hospital death. NYHA
      class improved from 3.2 to 1.8 (p < 0.05). The degree of MR was reduced from 3.5
      to 1.2 (p < 0.05), and left ventricular end-diastolic pressure decreased from 18
      +/- 7 to 13 +/- 8 mmHg (p < 0.05). Left ventricular fractional shortening,
      ejection fraction and cardiac index (2.4 +/- 0.4 to 2.7 +/- 1.1 l/min/m2) did not
      change significantly. Two patients died within one year due to exacerbation of
      congestive heart failure (2.5 month later) or sudden death (6 months later).
      Three patients died at 21 months, 5 and 8 years after the operation (renal
      insufficiency, heart failure, sudden death, respectively). Mitral reconstruction
      improved the symptoms in patients with DCM and severe MR in the short term.
      However, 5 of 6 patients died in the intermediate or long-term. Mitral
      reconstruction may be a therapeutic option for early outcome in patients with
      refractory congestive heart failure due to DCM and severe MR.

PMID- 9914959
TI  - [Therapy and physiopathology of hypertension in elderly].

PMID- 9914958
TI  - [Impaired left ventricular function in a patient with visual disturbance].

PMID- 9914960
TI  - [DNA repair and carcinogenesis: universal mechanisms for repair in pro- and
      eukaryotes and consequences of the damage in humans].

PMID- 9914961
TI  - [Ribosomal structure: RNA-protein and protein-protein interactions].

PMID- 9914962
TI  - [Dynamics of the diversity of the Asian Mongoloid population mitochondrial gene
      pool from data on the variability of hypervariable segment I].

PMID- 9914963
TI  - [Conformational changes of a transcription complex of RNA-polymerase with DNA].

PMID- 9914964
TI  - [EcoRII restriction endonuclease hydrolyses one of two recognition segments in
      DNA, forming a catalytic complex].

PMID- 9914965
TI  - [Structure-functional organization of exopolysaccharide biosynthetic genes in
      Rhizobium leguminosarum bv. viciae VF39].

PMID- 9914966
TI  - [DNA fingerprinting of the lizard Lacerta dahli: isolation of a genomic
      polymorphism of mini- and microsatellite loci].

PMID- 9914968
TI  - [Comparative analysis of the structure and retrotransposable activity of two
      variants of the Drosophila melanogaster MDG4 (gypsy) mobile element].

PMID- 9914967
TI  - [Identification of HLA DQA1 alleles by hybridization with oligonucleotide
      microchips].

PMID- 9914969
TI  - [Induction of synthesis specific for females of variants growth hormone receptor
      mRNA in liver of male rats].

PMID- 9914970
TI  - [Covalent binding of RNA with peptides in the structure of a specific complex
      using N-oxybenzotriazole oligoribonucleotide esters].

PMID- 9914971
TI  - [Complexes of intercalating dyes with parallel 5'-d(CATGCTAACT)-L-d(AGTTAGCATG)-L
      d(CATGCTAACT)-3'- and antiparallel 5'-d(A)10-L-d(T)10-L-d(T)10-3' triplexes of
      DNA].

PMID- 9914972
TI  - [Kinetic mechanisms of binding of cis-dichlorodiamminplatinum (II) and its mono
      hydrate form with oligonucleotides].

PMID- 9914973
TI  - [Heterogeneity of strong binding sites of ethidium bromide to DNA. fluorescing
      and nonfluorescing complexes].

PMID- 9914974
TI  - [Interaction of peptides of human immunodeficiency viral proteins with continuous
      cell lines of varying origin].

PMID- 9914975
TI  - [Specificity of DNA-protein interactions during formation of rosette-like
      structures (elementary chromomeres) and during association of interphase
      chromosomes with the nuclear envelope].

PMID- 9914976
TI  - [Distribution of tryptophanyl-tRNA-synthetase in cultured human monocytes after
      treatment with interferons].

PMID- 9914977
TI  - [Comparative study of fragments of chromosomal DNA, isolated from the nuclear
      lamina, core of rosette-like structures (elementary chromomeres), MARs/SARs and
      synaptonemal complex using a series of simple nucleotide motifs].

PMID- 9914978
TI  - [Species diversity of picoplankton from Lake Baikal by comparative analysis of 5'
      terminal segments of 16S rRNA genes].

PMID- 9914979
TI  - [beta-Fructosidases: a new superfamily of glycosyl-hydrolases].

PMID- 9914980
TI  - [Class M immunoglobulins from blood serum of patients with systemic lupus
      erythematosus effectively cleave RNA].

PMID- 9914981
TI  - [Detection and typing of the genome of Marek's disease virus using polymerase
      chain reaction].

PMID- 9914983
TI  - [Principles of the structural organization of the chemosensory system of
      freshwater gastropod mollusks].
AB  - Authors own experimental data and data available in literature were summarised to
      elucidate the influence of the mollusc environment and mode of living on
      structural organization of tentacular and osphradial systems, receptors of the
      mouth labia and mantle in typical freshwater mollusc. The similarity between
      sensory systems of tentacles, mouth and labia was demonstrated based on the
      findings obtained using silver impregnation, horse radish peroxidase labelling
      and electron microscopy. Module pattern of organization and peculiarities of
      sensory organs efferent innervation were demonstrated. Bilateral symmetry and the
      basis of multichannel structures of sensory systems central regions were
      described. Specific pattern of structural organization and those common with
      other animals were shown. The emphasis was made on differences from the olfactory
      systems of ground gastropods that consist in the lack of olfactory glomeruli, the
      special olfactory centres, procerebri and specialized chemosensory epithelium in
      freshwater mollusc.

PMID- 9914984
TI  - [Dynamics of thickness and width of the scar after suturing the wound of the
      stomach wall with different methods of external protection of the penetrating
      suture in an experiment].
AB  - The results of morphometric study of the effect of one-row penetrating suture
      external protection with musculoserous sutures, flap of the great omentum on
      vascular peduncle, surgical glue "Sulfacrilat" and collagenic explant "Sanguicol"
      in necrotic gastric wounds of 79 rabbits were represented. Single orientation of
      dynamics of the scar width and thickness under protection with the great omentum
      flap, surgical glue and collagenic explant and peculiarities of their dynamics in
      peritonization with musculoserous sutures were demonstrated. In submucosal coat
      the scar width was shown to exceed those in muscular one during initial period of
      the intervention and heterochronous convergention of the scar width in the
      gastric wall layers dependent on the method of external protection was discovered
      as well.

PMID- 9914982
TI  - [A method for preparing microchips using copolymerization with acrylamide].

PMID- 9914985
TI  - [Morphometric characterization of median brain structures using intravital
      magnetic resonance tomography].
AB  - Linear parameters of corpus callosum and submucosal structures (transparent
      septum, cupula, thalamus, pineal body and the third ventricle choroid plexus)
      were measured using 80 MR tomograms and 40 craniograms of 20 patients aged 20-50.
      Linear parameters were compared with the cranium shape and statistically
      processed. The dependence of linear parameters of the structures mentioned upon
      the shape of the cranium was demonstrated. They were characterized
      morphometrically in dolychomeso- and brachiocephals. The data obtained are of
      interest in assessment of MR tomograms with pathological changes and
      individualization of surgical interventions in median structures of brain.

PMID- 9914986
TI  - [Ultrastructure of the blood-brain barrier in the cerebral cortex in
      atherosclerotic dementia].
AB  - Ultrastructural changes of blood-brain barrier elements were studied in the
      cortex of cerebral superior frontal and medial temporal gyri in atherosclerotic
      dementia. Destructive changes in endotheliocytes, pericytes, basement membrane
      and increase in number, swelling and edema of astrocyte peduncles with the
      inconstant approximation of astrocyte body to the capillary basement membrane
      were demonstrated along with signs of blood circulation decline in cortical
      capillaries. Lipofuscin and lipids accumulation and aggregation of homogenous
      material of high electron density, probably plasma proteins, were characteristic
      for changes in blood-brain barrier in atherosclerotic dementia, which is
      important in pathogenesis of this type of the disease.

PMID- 9914987
TI  - [Long-term morphofunctional preservation of guinea pig hippocampal slices
      following short-term treatment with cyclooxygenase inhibitors].
AB  - Hippocampal slices treated with cyclooxygenase inhibitor indomethacin for three
      min during the sectioning (45 min) or aspirin (0.5 min) in long term (up to 5
      days) preservation in periodic nocturnal hypothermia were studied
      morphofunctionally using light microscopy and electrophysiological registration
      of induced population responses of area CAI to stimulation of Schaffers
      collaterals. Structural disorders were revealed in control slices as early as the
      third hour of incubation and they were destroyed following the first hypothermal
      challenge (24 hrs following preparation). The structure in slices treated with
      blockers remained more stable as compared to control ones and the activity was
      registered until d 3 (aspirin) and 5 (indomethacin). Morphological changes were
      not immediately, followed by electric activity decline. On the whole it may be
      suggested that essential viability increase occurred due to destructive processes
      inhibition mediated by short living cyclooxygenase metabolites.

PMID- 9914988
TI  - [Innervation of grouped lymphoid nodules (Peyer's patches) by the enteric nervous
      system and the topography of their interior neural elements in the rat].
AB  - Using the complex of histological methods (staining with toluidine blue, silver
      nitrate impregnation and application of retrograde fluorescent dye primulin) the
      data on the neural elements spatial localization within Peyer patches of the
      small intestine and their connections with the rest of enteric metasympathetic
      nervous system in rat was obtained. Submucosal plexus that is significantly
      developed within this lymphoid organ and is divided into internal and external
      plexuses was found to be most essential to the innervation of rat Peyers patches.
      These plexuses innervate all Peyers patch areas:nodules, cupula and internodular
      zones and the nodule-associated epithelium. Moreover, it was shown that within
      Peyers patch the plexuses form an integral part with the rest of the enteric
      nervous system and possess close connections with ganglia that are distant from
      the patch and are related both to submucosal and myenteric nervous plexuses.
      Direct inputs into Peyers patch nervous plexuses from extramural ganglia are
      present as well. These data was considered as a morphological basis for
      functional interaction of nervous and immune systems within the enteric immune
      organ and for possible enteric nervous system regulation of immune functions.

PMID- 9914989
TI  - [Structural changes in the pelvic plexus in cold stress].
AB  - Alterations caused by hypothermal stress in neurons of pelvic plexus in rats were
      studied histochemically. The increase of catecholamine content in neurons and
      serotonin--in small intensely fluorescent cells (SIFC), suppression of acetyl
      cholinesterase activity in neurons were demonstrated after the short-term
      hypothermal stress leading to moderate hypothermia. Cooling of rats following the
      preliminary section of pelvic nerves does not prevent the above mentioned changes
      in neurons and SIFC. The participant of adrenergic nerves and SIFC in peripheral
      mechanisms of thermoregulation is under discussion.

PMID- 9914990
TI  - [Topographic anatomy of the Lockwood ligament].
AB  - The study was performed using four cadavers of adult persons with the method of
      preparation. The access to the ligament was obtained by the removal of the
      inferior orbital wall and inferior orbital adiposal layer. Topographical anatomy
      of Lockwood ligament, its interrelations with inferior rectus and oblique muscles
      and attachment to lateral and medial orbital walls were studied. Lockwood
      ligament, the transverse fascial structure that supports the eyeball, stabilizes
      it, providing the framework for inferior rectus and oblique muscles of the eye.

PMID- 9914991
TI  - [Connective tissue components of conducting and working myocardium of the
      sinoatrial region of the heart in patients of various ages with idiopathic long
      QT syndrome (quantitative evaluation)].
AB  - Ultrastructural analysis of cells, collagen and elastic fibres and connective
      tissue matrix was performed separately in sinoatrial node (SN) and the right
      atrium (RA) perinodal working myocardium in 12 patients of different age with
      idiopathic long Q-T syndrome. Despite the variability in SN and RA connective
      tissue component content in different patients these parameters were often
      significantly different for working and conducting myocardium. In senior group SN
      and RA elastic fibres content showed 1.9 and 1.8 (P < 0.05) fold increase,
      respectively, although RA collagen fibres content was 2.2 fold (P < 0.02) lower
      as compared to younger patients. In general, difference of SN from RA was noted
      in 3 parameters of the 4 assessed, with the content of cells, collagen fibres and
      connective tissue matrix in conducting myocardium exceeding those in working
      myocardium.

PMID- 9914992
TI  - [Topography of the major vessels of the pelvic cavity and pelvic limb in albino
      rats using phase x-ray].
AB  - Findings of the phase X-ray examination of pelvic organs and pelvic limb vascular
      bed in albino rats are presented. The method suggested allows to observe arterial
      and venous vascular bed using blood substitutes instead of iodine-containing
      contrast substances and opens the perspectives for the new type angiography
      development. Additionally, it gives an opportunity to observe lymphatic vessels
      and nerve fibres.

PMID- 9914993
TI  - [Morphogenesis of the vena cava inferior roots in human embryogenesis].
AB  - The roots of the vena cava inferior are formed during the 2nd month of human
      embryogenesis in the course of transformation of posterior caudal veins and their
      tributaries, including anastomoses with umbilical veins, which is associated with
      the growth of pelvic kidney and lower extremities. The roots and initial part of
      vena cava inferior originate from secondary cardinal veins, primarily from
      sacrocardinal anastomosis and sacrocardinal veins proximal regions.

PMID- 9914994
TI  - [Morphologic changes in the thrombus and venous wall in experimental
      phleobothrombosis and thrombophlebitis].
AB  - Phlebothrombosis and thrombophlebitis were induced in dogs by percutaneous
      intraoperative introduction of thrombotic mass, obtained in vivo (20-40 animal
      blood per 3-4 ml thrombin solution) into jugular vein and studied in
      postoperative days 1, 3, 5, 7, 10 and 14 through light microscope. The
      preparations were stained with hematoxylin and eosin and after Hart, Van-Gieson
      and MSB. Venous intima was established to alter already on the next day following
      thrombophlebitis modeling. On d 3 and 5 epithelium desquamation and moderate
      leukocytic infiltration of media between smooth myocytes were found. On d 7 signs
      of thrombus organization, i.e. invasion of fibroblastic series cells and small
      capillaries inside it, were demonstrated. Muscular layer and adventitia display
      leukocytic infiltration. Venous wall thickens due to disorders of blood passage
      in vasa vasorum. On d 10 the portion of the thrombus attached to the wall was
      essentially organized. Fibroblasts and capillaries invade inside the thrombus,
      connective tissue fibres are formed. Sclerotic changes were noted in adventitia.
      By the end of the 2nd week venous wall showed muscular layer atrophia and
      sclerosis. Middle portions of the thrombus were involved in organization, canals
      lined with endothelium are formed in it. In case of thrombophlebitis changes in
      thrombus and venous wall develop earlier and are more pronounced.

PMID- 9914995
TI  - [Myocardial capillary bed in the cat after exposure to obsidan].
AB  - In studying the effect of physiologically active substances and pharmacological
      drugs the response of hemomicrovessels is of special interest. Calcium-adenosine
      triphosphatase method reveals all the branches of the organ hemomicrocirculatory
      bed simultaneously and the possibility to carry out a combined pharmacological
      and histoangiological study of intraorgan vascular bed is obtained. During the
      study on the obsidan effect on myocardial vascular bed of the cat it was
      established that obsidan causes major vessels dilatation and capillary
      constriction.

PMID- 9914996
TI  - [Comparative characteristics of renal microangioarchitecture in isolated and
      multiple sources of blood supply by age].
AB  - Using injection methods 39 autopsy kidneys obtained from healthy individuals of
      both sexes during 1st and 2nd periods of maturity were studied. In every age
      group kidneys with single artery and with many arteries were identified. Certain
      peculiarities of the kidney microangioarchitecture in cases with multiple sources
      of vascularization were established; age changes of renal microvessels were
      described.

PMID- 9914997
TI  - [Formation and development of prostatic hemomicrocirculatory bed in children and
      young men].
AB  - Age changes of the human prostate hemomicrocirculatory bed from 20 weeks of
      embryogenesis up to the 22 years of age were studied by histological,
      histochemical and morphometric methods in 113 prostatic glands. Two types of
      microcirculatory systems were established to be present in human prostate by the
      moment of birth: microvasculo-glandular complexes in lateral and posterior
      regions and myomicrovascular complexes, located basically in anterior regions of
      the gland. During neonatal and pubertal periods, when essential changes in organ
      structure occur, microcirculatory bed reacts by vessels dilatation. The greatest
      growth of all hemomicrocirculatory bed branches occur at the age of 13-16 years.
      In young men widened capillaries located as processes radiating from the
      glandular lumen and separated from them by a single layer of secretory cells
      appear in initial regions of glands.

PMID- 9914998
TI  - [Microcirculatory bed of the rat ovary in health and under laser irradiation].
AB  - Ovarian microcirculatory bed was studied using the method of scanning electron
      microscopy in albino rats during the helium-neon laser irradiation (632.7 nm wave
      length 0.76) 1 and 60 minutes long. Laser irradiation causes significant
      reorganization in the intraovarian vascular bed: capillaries become tortuous,
      relative section area, occupied by microvessels, grows significantly.
      Irradiation, elongated up to 60 min leads to stable increase of capillary
      diameter and appearance of pulsions along the capillary course.

PMID- 9914999
TI  - [Laryngeal extra-organic lymphatic vessels in postnatal ontogenesis].
AB  - Extralaryngeal lymphatic vessels were studied in normal conditions in 44
      cadaveric preparations obtained from people who died aged from 17 up to 91 using
      polychrome interstitial injection of Herot mass into laryngeal mucosa with the
      following anatomic preparation of extraorganic lymphatic vessels of larynx and
      lymphatic nodes. Average number of extralaryngeal lymphatic vessels was found to
      be minimal in senile age. Their content was asymmetric from right and from left
      in 70.5% cases, in 30.6% of which there was a predominance of left-side
      asymmetry. In women the number of extraorganic lymphatic vessels tended to grow.
      Mean number of extraorganic lymphatic vessels changes differently in men and
      women. In men significant decline in extralaryngeal lymphatic vessels occur from
      teenage up to senile period, in women vessel number tend to grow from the second
      period of maturity while average number of extraorganic lymphatic vessels
      significantly reduces.

PMID- 9915000
TI  - [Splenic lymphoid tissue of mice after irradiation with fast carbon ions].
AB  - Reorganization of cellular content of splenic functional zones was studied
      morphometrically in mice after single irradiation with fast carbon ions. It was
      demonstrated that irradiation does not cause significant changes in
      microtopography of splenic structures but is accompanied with changes in
      cytoarchitecture and rearrangement of lymphoid cells throughout the experiment.
      Two arbitrary stages are determined in lymphoid tissue response. The first one
      (30 hrs-7 d) is characterized with destructive processes intensification and
      decrease of small lymphocytes number in all functional zones of the organ. Strong
      plasmocellular reaction was observed in the organ except for the lymphoid nodules
      mantle zone in this period as well. On the second stage (15-60 d) orientation of
      plasmocellular reaction changes along with the tendency of small lymphocytes to
      restore population (up to 57-79% from the control level on d 60 of the
      experiment. As a result plasma cell content decreases sharply in all the organ
      structures. Low level of lymphocytopoiesis was demonstrated in the course of the
      experiment resulting from cell mitotic activity decline following the
      irradiation. At the distant period (d 60 following the irradiation) another
      decrease of cell lymphoid population was noted, which indicates that irradiation
      with fast carbon ions is suppressive to the animal immune system.

PMID- 9915001
TI  - [Features of the structure and parameters of the intra-alveolar septa in
      residents of Western Siberia].
AB  - In inhabitants of Novosibirsk and Moscow district intraalveolar septum, the basic
      functional element of the lung consists of interstitial connective tissue and
      capillar network, limited with basement membranes, on which cells of epithelial
      lining are placed. There are no principal differences in septal structure between
      individuals from both regions. The majority of morphometric parameters are
      statistically similar, although certain peculiarities were noted in human
      subjects from Siberia, the most important of which is that air-blood barrier in
      them is 33% thinner than those in inhabitants of Moscow district. Majority of
      capillaries possess the air-blood barrier from both sides. This increases diffous
      capacity of the lungs and blood oxygenation level.

PMID- 9915002
TI  - [Anatomy and histotopography of human pericardial lymphoid tissue].
AB  - Data concerning microscopic structure of the layers of human serous pericardium,
      localization of lymphoid structures as related to them and their interrelations
      with connective tissue elements and vessels are represented. Findings on the
      thickness of serous pericardium in different layers are also given.

PMID- 9915003
TI  - [Features of the distribution of lymphoid tissue in the walls of the trachea and
      principal bronchi after exposure to acetaldehyde vapors].
AB  - The present study was aimed to examine the lymphoid tissue in the walls of the
      trachea and major bronchi following the inhalation of acetaldehyde. Albino Wistar
      rats, subjected to the action of acetaldehyde 20 and 25 mgm/m3 in concentrations
      during 2, 4, 6, and 8 hrs were the subject of the experiment. It was established
      that acetaldehyde action in the wall of trachea and major bronchi results in
      histotopographical changes of lymphoid structures and increase of relative (%)
      area of lymphoid tissue in the walls of the above-mentioned organs.

PMID- 9915004
TI  - [Modification of methods of histochemical detection of the microcirculatory bed
      in the brain of laboratory animals].

PMID- 9915005
TI  - [Nitric oxide and its importance in the regulation of pulmonary function].

PMID- 9915006
TI  - [Clinical trends and use of current technology in teaching histology, cytology
      and embryology].

PMID- 9915008
TI  - Special international buyers' guide issue for 1999.

PMID- 9915007
TI  - [Sixty-fifth anniversary of the department of human anatomy at the Dagestan State
      Medical Academy].

PMID- 9915009
TI  - [Medical treatment of secretory hypophyseal adenomas].
AB  - The main indication for medical treatment of the secretory pituitary adenomas is
      macroprolactinoma. In this case, bromocriptine therapy obtains better results
      than surgery, by a life-long administration. New dopaminergic drugs with better
      tolerance and a longer half-life than bromocriptine will probably improve
      compliance to treatment. Besides, somatostatin analogs, especially the slowly
      released preparations, administrated once or twice per month, often obtain
      normalization of hormonal production in GH (growth hormone) or TSH (thyrotropin)
      secreting adenomas after surgical failure and are used in complement to
      radiotherapy.

PMID- 9915010
TI  - [Unilateral endonasal approach to hypophyseal adenomas].
AB  - The endonasal approach for transsphenoidal hypophysectomy is a simple technique
      for exposing the floor of the sella turcica. In our institution we have operated
      162 patients (64 microadenomas and 98 macroadenomas), over a ten-year period, by
      using that approach. The floor of the sella turcica is exposed through an
      incision performed posteriorly to the nostril at the junction of cartilaginous
      and bony septum. Postoperative rhinological complications are less frequently
      observed after unilateral endonasal approach than after sublabial one, and it is
      more comfortable for the patient. The morbidity of unilateral endonasal
      transsphenoidal approach is comparable to that of other series.

PMID- 9915011
TI  - [Unusual approaches to hypophyseal adenomas].
AB  - For pituitary adenomas surgery, rhinoseptal transsphenoidal approach is used in
      98 to 99% of the cases. Although this approach is fitting for microadenomas and
      the majority of macroadenomas, some of them develop extensions in the nasal
      fossas, the posterior cranial fossa, the suprasellar region, or into the
      cavernous sinus and will require other approaches. For the superior routes, the
      frontopterional approach gives good control of the suprasellar region, the
      anterior and middle base of the skull. The tumor dissection is performed inside
      the concavity of the chiasm and between the internal carotid artery and the optic
      nerve (optico-carotid approach). The frontopterional approach is used for
      superolateral extensions, especially in the lateral fissure. The bifrontal basal
      inter hemispheric approach, through a medial frontal bone flap tangential to the
      base, gives a good route to the suprasellar region and behind the dorsum, and
      also for tumors extended in the third ventricle in case of prefixed chiasm. For
      the inferior routes, the participation of ENT or craniofacial surgeons is a great
      help. The transfacial or transethmoidal approach performs a hollowing of the
      nasal fossas and gives a large interorbital tunnel adapted for tumors extended in
      the rhinopharynx and the ethmoid. The Le Fort I maxillary osteotomy offers also a
      large approach for adenomas extending in the rhinopharynx. The transcavernous
      approach from Dolenc, for adenomas progressing in the cavernous sinus requires a
      long and difficult procedure. The progression of some adenomas in many directions
      may require a combined approach in one or two procedures.

PMID- 9915012
TI  - [Use of endoscopy in pituitary surgery].
AB  - Endoscopy has changed many of surgical procedures concerning nasal and paranasal
      cavities. It has been proposed for transnasal removal of pituitary adenomas. The
      authors report their experience concerning four pituitary macroadenomas operated
      with the neurosurgical team of Sainte-Anne hospital. The endonasal trans-septal
      route seemed to be more anatomical and less traumatic than the rhinoseptal
      sublabial route. The 30 degrees rigid Hopkins endoscope was a good help for
      controlling the absence of any tumor remnant in the supra and parasellar regions
      after complete removal of the tumor performed through the endoscope or with the
      operating microscope. The authors discuss the advantages and limitations of such
      endoscopic procedures in the light of recent literature.

PMID- 9915013
TI  - Interactive image-guided pituitary surgery. An experience of 101 procedures.
AB  - This paper reports on a series of 101 pituitary region operations performed using
      image guidance technology in the Department of Neurosurgery, Frenchay hospital,
      Bristol, UK between 1992-1997. The cases form part of an overall series of image
      guided surgery of 1,112 cases performed during that time. The systems used were
      the ISG/Elekta Viewing Wand and the Sofamor Danek StealthStation. Thirty-five
      tumors had a diameter of > 2.5 cm and 12 > 5 cm. The clinical indications for
      surgery were: visual failure (n = 47), acromegaly (n = 22). Cushing syndrome (n =
      6), hyperprolactinemia (n = 1), hyposecretion syndromes (n = 8), raised
      intracranial pressure/CSF leak (n = 13). Three cases were operated on because of
      radiological evidence of tumor progression without symptoms. Eighty-five patients
      had skull base procedures (56 transnasal routes, 16 transsphenoidal approaches,
      13 sphenoid fenestrations), 16 underwent craniotomy. Operating times and
      postoperative bed stay were shortest the more minimally invasive the procedure.
      Sixty-eight percent of patients presenting with visual failure improved
      postoperatively. Surgery produced biochemical "cure" in 41% of patients with
      hypersecretion syndromes. Fifty percent of patients with hypopituitary syndromes
      improved endocrinologically postoperatively. Twenty-five complications were
      noted: 9 rhinorrheas, 5 diabetes insipidus, 3 postoperative epilepsies, 3 induced
      visual deteriorations and pituitary insufficiency. There were 2 deaths. Image
      guidance technology is applicable to pituitary surgery, particularly in four
      situations: i) orientation in difficult skull base approaches e.g. reoperations,
      paediatric cases, non pneumatised sphenoid, microadenomas, carotid arteries
      medially placed, ii) in craniotomies to customize the surgical approach, locate
      different parts of a tumor and identify critical anatomy related to the tumor,
      iii) in the planning and execution of minimally invasive approaches to the
      pituitary fossa (sphenoid fenestration, transnasal approach), iii) endoscopy.

PMID- 9915014
TI  - [The place of radiosurgery in the treatment of hypophyseal adenoma].
AB  - Since 1984, the neurosurgical team of Sainte-Anne Hospital in Paris has taken in
      charge almost 750 patients for linear accelerator radiosurgery. But only a small
      percentage of them were harbouring a pituitary tumor. That is why the present
      paper is based mostly on literature data. Pituitary adenoma radiosurgery (RS) is
      a second intention therapeutic method. It should be recommended only after
      failure of medical and/or surgical treatment. Two main methods can be used:
      linear accelerator-radiosurgery and Cobalt-60 gamma unit. Both procedures provide
      equivalent results in terms of dosimetry, accuracy and clinical data. Results of
      various series presented in recent and updated literature have been studied and
      analysed. They show and confirm the efficiency of radiosurgery on tumor and
      hormone secretion controls, with few cases of pituitary insufficiency. However,
      results were disappointing concerning visual disorders, particularly if visual
      dysfunction and impairment existed before radiosurgery. All authors agree
      nowadays on different points: a) indications: invasive adenomas, with an
      incomplete resection, or adenomatous recurrences, b) contraindications: tumoral
      size > 20 mm, distance to visual pathways < 5 mm, c) imperative precautionary
      measures: less than 8 Gray must be delivered on visual pathways, less than 40
      Gray on oculomotor nerves. In some cases, stereotactic fractioned radiotherapy
      may be an alternative treatment for large tumors close to visual pathways.

PMID- 9915015
TI  - [Intracavernous extension of hypophyseal macroadenomas: infiltration or
      invagination?].
AB  - Frequency of intracavernous invasion by a pituitary adenoma varies from 9% to 40%
      depending on the publications. Without putting off the possibility of true
      intracavernous invasion, it seems less frequent than evocated on CT-Scan and/or
      MRI data. We studied 153 files of pituitary adenomas operated upon recently: 72
      prolactinomas (47.3%), 30 GH-secreting adenomas (19.7%), 7 corticotrop adenomas
      (4.6%), 44 non secreting adenomas (28.3%). 108 patients (70.4%) harboured a
      macroadenoma (diameter > 10 mm). A suprasellar expansion was seen 90 times on CT
      Scan and/or MRI views. 19 times (17.7% of macroadenomas, 12.5% of the whole
      series) MRI evocated an infiltration of one or both cavernous sinuses (CS). Such
      data were found 3 times before 1991, 16 times since 1991, i.e. since MRI is
      systematically performed preoperatively. Except in two patients who respectively
      presented with a large intraorbital or temporal expansion, we have not been able
      to confirm the reality of the intracavernous invasion. We think that most of CT
      Scan or MRI data of so-called intracavernous invasion correspond in fact to a
      compression or to a fingerglove invagination of the medial wall of the CS. In
      fact, anatomical studies by Harris & Rhoton (1976) and by Taptas (1990)
      demonstrated that such an invagination of the medial wall exists in almost one
      third of normal pituitary glands. These data must bring up to much carefulness
      when considering a possible pathological CS invasion by a macroadenoma.
      Therefore, it should be thoroughly assessed with anatomoradiological and radio
      surgical correlations.

PMID- 9915016
TI  - [Controversies in the management of operated pituitary macroadenomas].
AB  - BACKGROUND AND PURPOSE: Complete resection of a pituitary adenoma is feasible in
      almost 50 to 70% of cases. Dealing with the remnant is still controversial. Three
      positions can be discussed: second stage operation, radiation therapy, clinical
      and radiological follow-up. METHODS: Among 108 pituitary macroadenomas operated
      on during the last 10 years, 54 patients (50%) with partially removed tumors were
      studied. Three cases best illustrating the evolution of these remnants are
      reported. RESULTS: Late MRI performed 4 to 6 months postoperatively is more
      valuable than early MRI in the evaluation of these remnants, which can remain
      stable for a long period of time without any adjuvant treatment. CONCLUSION: MRI
      should be performed 4 to 6 months postoperatively. Rather than performing
      radiation therapy systematically for asymptomatic patients, these patients should
      be followed up at regular intervals and treated only in case of regrowth of the
      tumor.

PMID- 9915017
TI  - [5,000 years of the treatment of fractures].

PMID- 9915018
TI  - [Anything new in sports traumatology? Round table].

PMID- 9915019
TI  - [Focus on allografts and bone substitutes. Round table discussion of the Study
      Group of Bone Tissue Substitutes 1997].

PMID- 9915020
TI  - [Osteoarticular infections. The 1st joint reunion organized by the initiative of
      the INSERM Interface Committee--Orthopedics. Friday, 14 November 1997].

PMID- 9915021
TI  - [Complete hip prosthesis before 50 years of age].

PMID- 9915022
TI  - [Conservative treatment of fractures of the upper end of the humerus].

PMID- 9915023
TI  - Hepatitis B: a serious public health threat. Viral Hepatitis Prevention Board.

PMID- 9915024
TI  - From Cannes 1993 to the present.
AB  - In 1993 the Viral Hepatitis Prevention Board focused its attention on the serious
      threat hepatitis B poses to the community at large. The Cannes 1993 meeting
      "Action Towards Control of Hepatitis B as a Community Health Risk" was the first
      initiative and the springboard for other activities. The rationale behind
      universal hepatitis B vaccination strategies and the prerequisites for
      implementing these strategies were analyzed. Background information on country
      specific hepatitis B epidemiology and on the feasibility of vaccination
      strategies were presented and discussed. The congress participants concluded that
      it is insufficient and ineffective to focus a vaccination campaign on a limited
      subset of the population (the so-called 'risk groups'), and the need for
      universal hepatitis B immunization was clearly recognized. Since Cannes 1993 many
      countries have responded to the call for universal hepatitis B immunization. Many
      have performed economic evaluation studies, while others have initiated sero
      epidemiological studies to generate input data for burden of disease calculation.
      These studies indicate that epidemiological and economic arguments cannot be used
      to delay the implementation of universal hepatitis B vaccination. Some countries
      have improved their surveillance systems and included viral hepatitis in the
      surveillance programmes. Others have put hepatitis B on the political agenda.
      Where are we now? In the six years since the Global Advisory Group of the
      Expanded Programme on Immunization set 1997 as the target for integrating HB
      vaccination into national immunization programmes world-wide, more than 90
      countries have included hepatitis B vaccine as part of their routine infant or
      adolescent immunisation programmes. In the WHO European Region, Albania,
      Bulgaria, France, Germany, Italy, Luxembourg, Moldova, Poland, Portugal, Romania,
      Andora, Austria, Greece, Malta, Switzerland, Israel, Slovenia and Spain have
      implemented universal vaccination programmes. Belgium, the Netherlands and
      several other European countries are seriously studying the issues or are making
      budgetary provisions for the introduction of HB into their vaccination
      programmes. Most of the European countries which now use the vaccine routinely
      have started with adolescent immunization. Italy and France have begun with both
      adolescent and infant HB immunization. The rewards of effective implementation of
      immunization programmes in these countries are becoming apparent and their
      success offers an exemplary model for other countries. The deadline was 1997! In
      Europe, work remains to be done before interventions, that will bring us closer
      to the WHO goal of universal immunization and to the goal of controlling
      hepatitis B in the community, are implemented. To this end, the VHPB has
      continuously supported the efforts of countries in Europe to meet the WHO target
      by convening meetings of international experts and issuing publications on the
      prevention and control of viral hepatitis.

PMID- 9915025
TI  - Evolution of the Viral Hepatitis Prevention Board--VHPB.
AB  - The Viral Hepatitis Prevention Board (VHPB) was formed in 1992 to provide
      authoritative information and advice on hepatitis B as an occupational hazard and
      to act as a scientific lobby group to promote hepatitis B vaccination as part of
      an overall risk reduction strategy. The VHPB published Viral Hepatitis, a
      newsletter whose format and content was designed to appeal to both professional
      and lay readers seeking information on hepatitis. The VHPB was successful in
      lobbying the European Parliament to add the Code of Practice on Vaccination to
      legislation protecting workers from occupationally acquired infections. The first
      initiative on occupational hepatitis B culminated in an international congress in
      March 1993 and the publication of 'Hepatitis B as an Occupational Hazard' in the
      WHO occupational health series. Since 1993 the Board has discussed HBV as a
      community acquired infection; control of hepatitis A (HAV) and eligibility for
      hepatitis A vaccine and combined hepatitis A and B vaccines; hepatitis C; and
      reviewed progress towards the control of HBV and the adoption of universal
      vaccination programmes in countries of low endemicity. A major international
      congress in Cannes in November 1993 took stock of actions taken to control
      hepatitis B as a community health risk in industrialised countries. The
      constitution and membership of the Board underwent significant change at the end
      of 1994. A Secretarial was located within the Centre for the Evaluation of
      Vaccination at the University of Antwerp to deal with all administrative matters
      and publications in peer reviewed journals. The format of Viral Hepatitis was re
      focused to increase the scientific content. The Board extended its actions
      geographically in 1996 to include the countries of Central and Eastern Europe
      (CEE) and the Newly Independent States (NIS) of the former Soviet Union. The
      success of the VHPB has exceeded all the expectations of the founding members.
      The major focus of the annual programme of meetings and of publications remains
      on hepatitis B and its prevention through vaccination. But more and more the
      broad range of prevention and control strategies for all forms of hepatitis is
      dealt with.

PMID- 9915026
TI  - Hepatitis B: virus, pathogenesis and treatment.
AB  - The hepatitis B virus (HBV) is a coated, incompletely double-stranded DNA virus
      with some outstanding features. (1) All three coat proteins of HBV contain HBsAg,
      which is highly immunogenic inducing anti-HBs. These antibodies are protective
      for HBV outer cells (humoural immunity). Structural viral proteins induce
      specific T-lymphocytes, which are able to eliminate HBV-infected cells (cytotoxic
      T-cells; cellular immunity). (2) Intracellular HBV primarily causes little or no
      damage (non-cytopathogenic), which is an excellent strategy of viral survival.
      However, viral oligo-peptides of 8-15 amino acids are loaded on host cell MHC
      class 1 molecules and are transported to the cell surface. Thus, HBV-specific T
      lymphocytes are able to detect infected cells and destroy them, an ingenious
      defence strategy. However, this cell deletion triggered by inflammation cells may
      result in acute hepatitis. If HBV is not eliminated, a delicate balance between
      viral replication and immunodefence prevails which may lead to chronic hepatitis
      and liver cirrhosis. (3) In chronically infected cells HBV may become partly
      cytopathogenic--a process still poorly understood--and the viral DNA may
      integrate into the host cell DNA (through a viral transcriptase). If integration
      leads to activation of crucial host genes a hepatocellular carcinoma results.
      These outstanding features are responsible for the highly variable course of HBV
      infection and its final outcome, e.g. when the load of HBV-infected cells is
      still low at the time when an efficient immune defence starts, the infection is
      self-limited and asymptomatic, and immunity results. When there is no immune
      defence or a defective immune defence (immune tolerance of new-borns or
      immunosuppressed individuals) the HBV infection very often becomes chronic. In
      these cases, no acute hepatitis occurs, but hepatocellular carcinoma may result.
      Treatment with Interferon has become accepted, resulting in up to 30 to 40% of
      cases in the elimination of the virus. However, treatment is laborious and
      expensive, and the mechanism of action is still poorly understood (anti-viral
      and/or immune-modulating).

PMID- 9915027
TI  - Universal hepatitis B immunization: infant, and infant plus adolescent
      immunization.
AB  - Hepatitis B virus (HBV) is one of the world's most widespread infectious agents
      and the cause of millions of diseases and deaths each year. Vaccination
      programmes aimed at risk groups are important for individual protection, but will
      not eliminate viral transmission in Europe, since 70% of acute hepatitis B cases
      are either acquired by sexual activity or are of unknown origin. In
      industrialized countries, HBV infection occurs mainly in young adults, however,
      when the virus is acquired during infancy it leads to extremely high rates of
      chronic carriership, contributing disproportionately to the overall pool of HBsAg
      carriers. This explains why integrating universal HB vaccination into routine
      infant immunization programmes is the best means for controlling HB in countries
      with intermediate to high levels of HB endemicity. In countries of low
      endemicity, universal immunization of adolescents may be considered as an
      alternative to infant vaccination, as this strategy has a more rapid effect on
      the epidemiology of the infection. Where feasible, a double strategy (infant plus
      adolescent) is the optimal solution. With this strategy, adolescent immunization
      is necessary only for the time required for the first cohort of immunized infants
      to reach adolescence. After universal vaccination programmes have been
      implemented, efforts must be made to sustain vaccine procurement, monitor
      coverage, check the incidence of acute disease, particularly in immunized cohorts
      and verify by seroepidemiological studies the progression made in the elimination
      of HBV transmission.

PMID- 9915028
TI  - Universal hepatitis B immunization: young adolescent immunization.
AB  - Hepatitis B (HB) vaccines are safe and effective. To control HB infection at a
      population level, use of this vaccine in a routine immunization programme
      targeted at specific age groups has been recommended. Young adolescents (10 to 13
      yr of age) are a group which may well be considered for such a programme,
      especially if school-based. This paper outlines some of the rationale, advantages
      and disadvantages of targeting this age group for HB vaccine as well as providing
      some recommendations regarding operational matters related to such a programme.

PMID- 9915029
TI  - Hepatitis B vaccination of adolescent and adult high-risk groups in the United
      States.
AB  - Substantial progress has been made in implementing routine infant hepatitis B
      vaccination in the United States. However, in 1996, an estimated 65,000 acute
      hepatitis B cases occurred, the majority of which were among young adults in high
      risk groups. Recent surveys have found very low vaccination coverage among
      several high-risk groups, including men who have sex with men and patients with
      sexually transmitted diseases (STDs). Targeted vaccination of persons with risk
      factors for hepatitis B virus (HBV) infection can be provided in a variety of
      settings including family planning clinics, STD clinics, drug treatment centres,
      detention centres, jails and prisons. However, vaccination programmes have been
      infrequently implemented in these settings and the majority of persons with acute
      hepatitis B cases have had a missed opportunity for vaccination in the past.
      Thus, in order to accelerate elimination of HBV transmission in the United
      States, increased efforts are needed to implement effective hepatitis B
      vaccination programmes targeted to adolescents and adults in high-risk groups.

PMID- 9915030
TI  - Screening of pregnant women for hepatitis B.
AB  - Neonatal infection with hepatitis B virus carries a very high risk of resulting
      in a persistent infection. Babies born to hepatitis B carrier mothers are at risk
      of infection through exposure to blood and body fluids during birth. These 'at
      risk' babies can only be identified through screening of all mothers during
      pregnancy. Prevention of infection in this group is a key element in any nation's
      strategy to reduce the incidence and eventually eliminate hepatitis B infection
      in its population as the persistently infected infants are a reservoir of
      infection throughout their lives. The infected adult carries a relatively low
      risk of becoming a chronic carrier (< 10%). Various strategies for screening in
      pregnancy have been adopted. These include attempts to identify women with a
      history of 'risk behaviour', testing only women who were born in areas of high
      endemicity, pooling of sera and universal antenatal screening. The advantages and
      disadvantages of the various strategies will be discussed.

PMID- 9915031
TI  - Hepatitis B and blood safety.
AB  - The safety of blood and blood products is a global issue. Blood transfusion is an
      important part of modern medicine, but it is also an efficient route of
      transmission for a number of infectious agents. Although many countries screen
      all blood donations for a number of infectious agents, a significant proportion
      of the world's blood supply is either unscreened or poorly screened, with the
      resultant risk to recipients of transfusion transmitted infections (TTI).
      Hepatitis B virus (HBV) is of concern because it is transmitted parenterally,
      many HBV infections are asymptomatic (and infected individuals may thus
      unwittingly present as blood donors) and the virus is stable in blood and blood
      products over long periods. The transmission of HBV is minimized by the screening
      of donors prior to donation, exclusion of high-risk donors, followed by the in
      vitro screening of donations for HBsAg (+anti-HBc in some countries) prior to
      transfusion. However, even in countries with good quality, active screening
      programmes, there is still a small residual risk of transmission of HBV from
      undetected donors with early acute infection, resolving infection, silent
      infection or infection with atypical virus serology. Unfortunately, as with so
      many infectious agents, the prevalence of HBV is most often higher in those
      countries with poorly developed healthcare systems and limited resources. In
      these countries, the safety of the blood supply is compromised frequently, either
      because of lack of resources with which to purchase screening assays, or because
      of acute blood shortages and insufficient time to screen blood prior to
      transfusion. In such situations it is important to encourage and actively support
      the introduction of appropriate screening programmes which can be based upon
      simple assay formats, such as agglutination, rather than the favoured but more
      complex enzyme immunoassays which are more expensive, require specific equipment
      and support, and take longer to perform. Such approaches will help reduce greatly
      the transfusion transmission of HBV.

PMID- 9915032
TI  - Success stories in the implementation of universal hepatitis B vaccination: an
      update on Italy.
AB  - Compulsory universal vaccination against hepatitis B was introduced in 1991 in
      Italy for all newborns and 12-year-olds. Despite the decreasing circulation of
      the virus noted in the late-1980s, it was clear that only universal immunization
      would control hepatitis B infection and limit the transmission of the virus. Data
      collected during the first six years after vaccination was implemented show the
      success of the strategy. Over 90% of infants in the country and adolescents
      living in north-central Italy were immunized. Since 1995, the decrease in acute
      cases of hepatitis B has accelerated in the age groups 0-14 and 15-24,
      particularly in two regions of the north; during the same period, no comparable
      decrease in incidence was seen in older age groups. Monitoring coverage of
      vaccination and incidence of acute disease and seroepidemiological studies will
      continue and should show a rapid progression towards the elimination of HBV
      circulation in the country.

PMID- 9915033
TI  - Hepatitis B immunization programme: Spain.
AB  - Until the early 1990s, the hepatitis B prevention strategy in Spain was based
      exclusively on selective vaccination of high-risk groups. However, this strategy
      proved inadequate in reducing the incidence of disease and the prevalence rate of
      chronic carriers. In October 1991, the Autonomous Region of Catalonia embarked on
      a programme of universal immunization targeted at 12-year-olds. A few months
      later, in June 1992, the National Council on Health issued the recommendation
      that the "autonomous regions, taking into account their budgets and
      infrastructures, should establish HB immunization programmes for adolescents as
      soon as possible". Currently, the 17 autonomous regions are carrying out
      adolescent immunization programmes against HB.

PMID- 9915034
TI  - Hepatitis B immunization programme: lessons learnt in Greece.
AB  - Historically, Greece has had the highest burden of hepatitis B virus (HBV)
      infection in the European Union (EU). Heterosexual contact is the primary means
      of HBV transmission in Greece, accounting for approximately 30% of acute cases in
      adult males and 50% of acute cases in women of reproductive age [Kattamis C,
      Papevangelou G. Workshop Group: Greece. Vaccine 1995;13:S97-S98.]. In 1982,
      Greece implemented a hepatitis B prevention programme aimed at high-risk groups;
      unfortunately, this approach had little impact on disease incidence or
      prevalence. At the recommendation of the WHO and the World Health Assembly and
      after sustained lobbying by several scientific and medical associations in
      Greece, the Greek government decided to implement a national prevention programme
      for hepatitis B. The programme, in effect from early 1998, includes the screening
      of pregnant women, universal infant and adolescent immunization and immunization
      of high-risk groups.

PMID- 9915035
TI  - Progress toward elimination of hepatitis B virus transmission in the United
      States.
AB  - The strategy to eliminate hepatitis B virus (HBV) transmission in the United
      States is comprised of the following components: (1) preventing perinatal
      transmission, (2) routine infant vaccination, (3) catch-up vaccination of
      children in high-risk groups at any age, (4) catch-up vaccination of all children
      at 11-12 years of age and (5) vaccination of adolescents and adults in high-risk
      groups. According to recent surveys, > 85% of pregnant women are screened for
      hepatitis B surface antigen (HBsAg). Of infants born to HBsAg-positive women
      identified in 1995, 93% received appropriate immunoprophylaxis at birth; however,
      only 69% were fully vaccinated by 6-8 months of age. From 1991 (when routine
      infant hepatitis B vaccination was first recommended) to 1996, the proportion of
      19-35-month-old children who have received three doses of hepatitis B vaccine has
      increased from < 10 to 83%. During this time, rates of acute hepatitis B in
      children 7-10 years of age have declined by 27% and rates among children 3-6
      years of age have declined by 62%. Implementation of programmes for catch-up
      vaccination of all adolescents at 11-12 years of age and for vaccination of
      adolescents and adults in high-risk groups have only recently begun and no data
      are available to assess the progress of these programmes. However, 26% (13/50) of
      states now have laws requiring adolescents to be vaccinated in order to enter
      school. Current data indicate that substantial progress has been made in
      implementing a strategy to eliminate HBV transmission in the United States.
      Future efforts need to be focused on improving complete immunoprophylaxis of
      infants of HBsAg-positive mothers, increasing vaccine coverage among 11-12 year
      old children and implementing programmes to vaccine adolescents and adults in
      high-risk groups.

PMID- 9915036
TI  - Control of hepatitis B in the United Kingdom.
AB  - Control of hepatitis B in the UK is based upon selective vaccination of persons
      in high-risk groups. To assess the likely cost-effectiveness of changes to this
      policy, information on the current burden of HBV infection in the UK is required.
      Laboratory reports of acute hepatitis B suggest that the vast majority of new
      hepatitis B infections acquired in the UK occur in adults, even after adjustment
      for unapparent infection. In childhood, perinatal transmission remains the most
      significant known risk factor. Universal antenatal screening has the potential to
      prevent perinatal infections in UK births and a substantial proportion of those
      UK acquired infections which lead to carriage. In addition, to antenatal
      screening, universal infant vaccination (at 2, 3 and 4 months) can, in the short
      term, only prevent the small number of infections acquired in childhood. Economic
      analysis using current surveillance data is required to assess the possible cost
      benefit of universal vaccination. Regardless of this, there is an urgent need to
      improve selective vaccination and to ensure that a high proportion of antenatal
      carriers is identified.

PMID- 9915037
TI  - Why the Scandinavian countries have not implemented universal vaccination against
      hepatitis B.
AB  - Within the 50 member states of the WHO European region, HBsAg carriage rates vary
      from a high of approximately 20% to a low of 0.05%. The Scandinavian countries
      have the lowest carriage rates in the region (0.05%). The situation in Sweden is
      representative of the situation throughout Scandinavia: although a substantial
      number of immigrants to Sweden are HBsAg-positive, acute cases of hepatitis B
      continue to be seen mainly in drug addicts and their contacts and to a certain
      extent, in male homosexuals with multiple partners. Public health officials and
      governments in Scandinavia are unwilling to introduce universal vaccination of
      infants because hepatitis B infection is viewed as a limited public health
      problem that does not justify the expense and other efforts of universal
      immunization.

PMID- 9915038
TI  - Report on Working Group 1: Albania, Andorra, Canada, France, Italy, Moldova,
      Portugal, Poland, Romania and Spain.

PMID- 9915039
TI  - Report on Working Group 2: Austria, Belgium, Bulgaria, Germany, Greece, Hungary,
      Malta, Russia, Switzerland, Turkey and Uzbekistan.

PMID- 9915040
TI  - Report from Working Group 3 (the Czech Republic, Denmark, Finland, Norway, The
      Netherlands, Slovakia, Sweden and the UK).
AB  - The Czech Republic, Denmark, Finland, Norway, the Netherlands, Slovakia, Sweden
      and the UK all have very low HBsAg carrier rates; in the Scandinavian countries,
      for instance, carrier rates are on the order of 0.05%. Most countries in this
      group are unconvinced that the carrier rates and the burden of disease caused by
      new hepatitis infections warrant the expense of universal childhood immunization.
      In Scandinavia and the UK hepatitis B prevention programmes are based on
      immunization of high-risk groups. In Scandinavia (excepting Denmark), the UK and
      the Netherlands, pregnant women are screened and newborns of carrier mothers
      vaccinated. Only the Czech Republic and Slovakia--both of which now employ high
      risk group strategies of hepatitis B prevention--have expressed interest in
      implementing programmes of universal hepatitis B vaccination of infants and/or
      adolescents.

PMID- 9915041
TI  - Novel hepatitis B vaccines.
AB  - Currently available hepatitis B vaccines are immunogenic, efficacious and safe.
      There is no doubt that their consistent use makes the elimination of hepatitis B
      in most countries possible. Nevertheless, there are still aspects of these
      vaccines which could be improved: three doses are needed for a full course of
      vaccination (which is sometimes difficult to achieve because of poor compliance
      or difficult logistic situations in some regions), there is a comparably high
      rate of non-responders to the vaccine (about 5% in adults) and, finally, it is
      not impossible that there are strains of HBV showing mutations of HBsAg which
      could escape the immunity induced by present vaccines. Work is underway to
      overcome these problems. Combined vaccines such as those providing protection
      against diphtheria, pertussis, tetanus, Haemophilus influenzae type b hepatitis B
      and poliomyelitis are an important step in simplifying hepatitis B vaccination of
      infants. Combined vaccines are already in use under clinical evaluation. In an
      effort to reduce the number of injections, two dose schedules with vaccines of
      higher dosages are being examined and single-dose vaccines encapsulated in
      degradable micro-particles of biopolymers (called slow-release vaccines) have
      been successfully tested in animals. Intense research is being conducted to
      enhance the immunogenicity of present vaccines. One possibility under
      investigation is the development of recombinant vaccines containing the complete
      preS1 and preS2 regions of HBsAg or immunogenic epitopes of these regions in
      addition to the small surface protein; several of such vaccines have already been
      tested in clinical trials. Future developments include expression of HBsAg
      determinants in bacteria, e.g., Salmonella, for oral vaccination or DNA vaccines
      against hepatitis B.

PMID- 9915042
TI  - Current combined vaccines with hepatitis B.
AB  - Hepatitis B (HB) vaccine has been included in the national immunization
      programmes of more than 90 countries world-wide. Its combination with DTP
      (diphtheria-tetanus-pertussis) and other childhood vaccines will lower
      administration costs, simplify vaccine administration and improve the logistics
      of vaccine delivery. It is believed that the combined vaccines will increase
      acceptance and vaccine coverage. The immunogenicity and reactogenicity of the
      various components should not differ when given separately or together. The
      combined vaccines DTP + HB, DT + HB, HA + HB, HB + Hib have already been
      developed and used in several countries and DTP + HB + IPV and DTP + HB + IPV +
      Hib combined vaccines are currently under development. Further studies are
      necessary to devise appropriate schedules adjusted to the epidemiological
      situations of each geographic region.

PMID- 9915043
TI  - Commentary: public perception and the safety of immunization.

PMID- 9915044
TI  - Surveillance of hepatitis B: an example of a vaccine preventable disease.
AB  - The objectives of surveillance for vaccine preventable disease vary with the
      stage of the vaccination programme. Pre-implementation data is required to
      estimate the burden of disease and to decide on the appropriate vaccination
      strategy. Post-implementation data is required to monitor effectiveness but when
      high coverage is achieved surveillance must be able to accurately identify
      remaining pockets of susceptible persons. Sources of data include clinical and
      laboratory reporting. In most countries, all vaccine preventable diseases
      (including acute viral hepatitis) are notifiable by law. Such systems are prone
      to under-reporting but are usually satisfactory for monitoring trends. To
      encourage the rapid tracing and vaccination of contacts of acute hepatitis B, a
      sensitive case definition and timely reporting system are required. A clinical
      definition (e.g. for viral hepatitis) may be too broad, however, to assess the
      impact of vaccination and additional laboratory criteria may be necessary. As a
      country nears elimination, the predictive value of any case definition will fall
      and laboratory confirmation will always be required to target policy
      appropriately. Serological surveillance is another method for estimating disease
      incidence. This may be useful for hepatitis B as tests can distinguish vaccine
      induced immunity from natural infection and acute from prevalent cases. To
      monitor vaccine impact, age-coded specimens can be collected on an intermittent
      basis. Where the incidence is low, however, this approach, will be very
      expensive. Surveillance of vaccine preventable disease therefore requires
      flexible surveillance systems which are able to adapt to changes in incidence of
      infection and in control policy. The use of multiple data sources and supportive
      information from special studies is essential for the valid interpretation of
      routine data.

PMID- 9915045
TI  - Assessing immunization coverage: how and why?
AB  - Assessment of immunization coverage is an important part of evaluating an
      immunization programme and it is a useful aid in programme management and
      decision making. Coverage assessment should be carried out at the national and
      district levels. Routine methods currently used in EU countries vary and are not
      always accurate, and should be validated regularly by specific surveys.

PMID- 9915046
TI  - Economic evaluations applied to HB vaccination: general observations.
AB  - Since HB vaccines became available, there have been many economic evaluations on
      HB vaccination programs. The majority of them were for countries of low
      endemicity. Economic evaluations for countries of very low endemicity with a good
      surveillance system in place and high attendance of Sexually Transmitted Disease-
      and Intra VenousDrug Users-clinics indicate that risk group vaccination is the
      most cost-effective strategy to control HB. In analyses for low endemic
      countries, recommendations have shifted from risk group vaccination in the
      eighties to universal vaccination of either infants or adolescents in the
      nineties. For the health care payer, the resulting cost-effectiveness ratios of
      universal vaccination were favourable in comparison to those of other preventive
      interventions. From a societal point of view, universal HB vaccination was found
      to be cost-saving in these countries. Few published studies were set in countries
      of intermediate to high endemicity. They indicate that for the health care payer
      universal HB vaccination of neonates or infants is cost-effective compared to
      other interventions, or even cost-saving. Further studies are needed to support
      decision making in high endemic countries, where both the need for HB vaccination
      and the pressure on resources are highest.

PMID- 9915047
TI  - Sustainable introduction of affordable new vaccines: the targeting strategy.
AB  - Immunization prevents over 3 million child deaths from vaccine preventable
      diseases such as diphtheria, pertussis, tetanus, measles and polio every year.
      New vaccines against respiratory and diarrhoeal diseases have the potential to
      prevent an additional 8 million deaths. Assuring that the existing and new
      vaccines are available to all children in the world is a global health priority.
      The health benefits of new vaccines like hepatitis B and Haemophilus influenzae
      type B (Hib) are indisputable. In the case of hepatitis B, over 1.2 millions
      deaths could be prevented each year if children and at risk adults were immunized
      with the hepatitis B vaccine. However, despite the clear health need and benefit,
      many countries have been unable to provide the 'new' vaccines, like hepatitis B
      vaccine, to their populations. For these countries, the limitation is not the
      delivery structure. Most countries now have immunization delivery structures
      which can provide immediate access to 80% of the country's newborns. Nor is it
      the vaccine availability as adequate capacity exists to meet the demand. The
      limitation has been the inability of governments to finance the vaccine because
      of a combination of factors including dependence on donors, donor policy,
      inadequate recognition by governments of the value of vaccines and, for some
      countries, the absolute price of the vaccines. The successes and failures in
      introducing a 'new' vaccine like hepatitis B vaccine into the world have clearly
      illustrated that it is economics and not epidemiology which dictates introduction
      of the vaccine into national immunization programmes. UNICEF and the WHO Global
      Programme for Vaccines and Immunization (GPV), have now developed and adopted a
      framework which differentiates countries based on their capacity to be
      financially self-sufficient for their vaccine needs. This framework forms the
      basis of strategies designed to co-ordinate the actions of governments, donors,
      agencies and vaccine manufacturers in order to ensure all countries have rapid
      access to affordable vaccines.

PMID- 9915048
TI  - Control of hepatitis B in central and eastern Europe (CEE) and the Newly
      Independent States (NIS): recommendations of the October 1996 meeting in Siofok,
      Hungary.
AB  - The prevention and control of hepatitis B virus (HBV) infection constitutes a
      major health policy priority especially in countries belonging to the CEE and the
      NIS (the former Soviet Union). Many of these countries report high prevalence
      rates of HBV infection, clinical disease and even high mortality. The Viral
      Hepatitis Prevention Board (VHPB) jointly organized with the World Health
      Organization (WHO) and the United States Centers for Disease Control and
      Prevention (CDC) a meeting to bring together managers of national immunization
      programs, hepatitis experts and senior officials from ministries of health. The
      meeting was held in Siofok, Hungary from 6 to 9 October 1996. The aim of the
      meeting was to put the prevention of hepatitis B on the political agenda and to
      speed up the progress of the countries in central and eastern Europe and the
      Newly Independent States towards the implementation of universal childhood
      vaccination against hepatitis B. The epidemiology of hepatitis B in the countries
      concerned was discussed, the different strategies for prevention of hepatitis B
      reviewed, major elements in priority setting elaborated, with emphasis on health
      economics and strategies for resource mobilization outlined: national and
      international experts exchanged views during six workshops (resource
      mobilization: monitoring and surveillance; vaccines and immunization; vaccine
      production, quality control and regulation issues; nosocomial transmission and
      diagnostics). A major outcome of the meeting was a consensus statement and
      recommendations for action. These recommendations concerned the countries of the
      region but also 'partners in development' and the WHO, insisting that the
      international agencies should support technically and financially the hepatitis B
      prevention efforts of the countries.

PMID- 9915049
TI  - Status of hepatitis B immunization programmes in 1998.
AB  - More than 90 countries have now included hepatitis B (HB) immunization into their
      National Immunization Programmes as a routine vaccine given to all infants and/or
      adolescents and many additional countries are planning for the introduction in
      the next two years. These countries include all industrial countries except the
      United Kingdom, Ireland, The Netherlands, the Scandinavian countries and Japan.
      Countries with routine HB immunization include about 45% of surviving new-borns,
      but almost 70% of hepatitis B virus carriers live in countries with routine HB
      programmes. Population based studies of HB immunization from around the world are
      now being reported with as long as 10 to 15 years of follow-up, showing a
      reduction of the chronic HB carrier prevalence from high (8% or greater) to low
      (less than 2%) endemicity in immunized cohorts of infants. Reductions in the
      price of HB vaccines, a significant increase in the number of producers and the
      advent of combination vaccines including an HB component will make the vaccine
      available to more children world wide, but economic constraints continue to
      hamper introduction of this vaccine to the children in the poorest countries.

PMID- 9915050
TI  - [Wounds of the heart].
AB  - The frequency of wounds of the heart as the cause of lethal outcomes on the
      battle-field practically has not changed during the recent 50 years and is equal
      to 80%. At the same time, the danger of such complications as infectious
      endocarditis has increased. The author's experience with surgical treatment of
      gunshot wounds of the heart makes 85 cases. Symptoms of intracardiac infection
      were detected in 74% of the wounded, 52 of them having the septic form.
      Operations were performed under artificial circulation. They included the
      extraction of foreign bodies, complex sanitation of the heart chambers and
      recovery of intracardiac hemodynamics. There were no lethal outcomes in the
      nearest postoperative period. Success of the treatment depends on terms of
      delivery of the patient to the hospital, quickness of surgical intervention and
      adequate intensive therapy.

PMID- 9915051
TI  - [The surgical treatment of postinfarct aneurysms of the left ventricle].
AB  - Operations for ischemic heart disease complicated by the appearance of
      postinfarction left ventricular aneurysm were fulfilled on 94 patients. The
      modified operation after V. Dor used in 55 patients allowed fulfilling
      interventions on the damaged parts of the interventricular septum excluding the
      application of foreign patches. Intrahospital lethality was 7.6%.

PMID- 9915052
TI  - [Procedures for the surgical treatment of cancer of the distal portions of the
      large intestine].
AB  - The authors observed 224 patients with neglected forms of carcinoma of distal
      portions of the colon, 171 (76.3%) of them being considered to be operable. The
      character of operative interventions depended on neglect of the tumour process
      which was determined by its spread to the neighbouring organs and tissues. The
      endolymphatic antibacterial therapy through the inguinal lymph node allowed the
      perifocal inflammation to be controlled which made the ablation of the tumour and
      the involved lymph nodes easier. The veritable ingrowth of the tumour into the
      neighbouring organs and tissues was noted in 15.4% of the patients. Radical
      operations were performed on 128 patients (74.9%), the other patients were
      submitted to palliative operations. The strategy of surgical treatment must be
      based upon the detailed diagnosis of the tumour growth and adequate preoperative
      preparation including endolymphatic infusions of antibacterial medicine. It
      allows to increase the amount of radical interventions and widen the indications
      for performing sphincter-saving operations.

PMID- 9915053
TI  - [Evacuatory motor disorders of the digestive tract in the early period after
      operations on the stomach (2. Evacuatory motor disorders of the small
      intestine)].
AB  - The method of telemetry was used for studying the motor function of the small
      intestine in 8 volunteers, 15 patients with duodenal ulcer before operation and
      in 43 patients at early terms after truncal vagotomy or resection of the stomach.
      During the first three days, irrespective of the kind of operation and of the
      degree of extraorganic denervation of the digestive tract, the motility of the
      small intestine has autonomic regimen of regulation, the pathognomic structure of
      the motor cycle and is characterized by sufficiently high contractility at the
      expense of frequent and regular generation of the migrating motor complexes. The
      motility is restored by the 10th-12th day. Functional evacuatory disturbances of
      a medium and grave degree are due to hypodynamia or transitory adynamia of the
      small intestine.

PMID- 9915054
TI  - [Chronic duodenostasis resulting from a mechanical obstacle in the area of
      Treitz's ligament].
AB  - An analysis of results of diagnosis, operative treatment and motility of the
      duodenum and jejunum was made in patients with chronic mechanical obstruction of
      the duodenum at the level of the Treitz ligament. In the period before operation
      of importance is the investigation of gastric secretion. Duodenojejunostomy is
      considered to be the most adequate intervention. In patients with higher indices
      of gastric secretion the main intervention is supplemented by some kind of
      vagotomy for prevention of peptic ulcer of the interintestinal anastomosis and of
      erosive gastritis. The motor and evacuatory function of the duodenum and jejunum
      after vagotomy is increased. The immediate and long-term results are good.

PMID- 9915055
TI  - [The treatment of peptic ulcers of gastrointestinal anastomoses].
AB  - Peptic ulcers of gastroenterostomies are a serious complication after resection
      of the stomach or gastrojejunostomy. Their appearance is always associated with
      the presence of considerable production of hydrochloric acid in the stomach,
      while the primary operations are performed, as a rule, for chronic ulcers of the
      duodenum. Choice of an adequate kind of treatment of these patients still remains
      an actual problem. The authors have obtained convincing data of good results of
      conservative treatment of patients with peptic ulcer of the anastomosis. However,
      surgery is considered to be the main method of treatment of this category of
      patients. Its success depends upon the correct detection of causes of the disease
      and use of the pathogenetically substantiated surgical interventions aimed at
      eradication of etiological factors.

PMID- 9915057
TI  - [Current aspects of the diagnosis and treatment of prostatic cancer].
AB  - Prostate cancer is becoming the most frequent malignant disease in men. Its
      present-day diagnosis in based on the combination of digital rectal examination,
      detection of the prostate-specific antigen in blood serum and multifocal
      transrectal biopsy of the prostate under ultrasonic control. The elevation of the
      level of prostate-specific antigen correlates with spread of the process and
      extracapsular penetration of the tumor. Asymmetry of the prostate and
      hypoechogenic foci represent the main ultrasonic signs of adenocarcinoma of the
      prostate. When the histological findings speak about the absence of atypical
      cells, another complex examination with rebiopsy is indicated in 6 months. The
      principal radical method of treatment of prostate cancer is prostatectomy
      performed mainly for the T1-T2 stages. At the preoperative period the neoadjuvant
      androgen deprivation can be performed in order to lessen the tumour volume and
      risk of a positive surgical margin.

PMID- 9915058
TI  - [The current status and developmental paths of surgical gynecology].
AB  - The article is devoted to actual problems of operative gynecology. Modern
      advantages in endoscopic, microsurgical, reconstructive-plastic surgery in
      gynecology are shown. Further improvement of the urogynecological operative
      technique remains to be an important task. The authors believe that the future
      belongs to organ-saving operations.

PMID- 9915056
TI  - [Current approaches to the diagnosis and treatment of residual
      choledocholithiasis].
AB  - Residual calculi were removed by different methods in 704 patients aged 22-86
      years having residual choledocholithiasis. The author considers non-operative
      eradication of it to be a preferable method for patients with the external drain
      of bile ducts, for patients without the drain endoscopic papillosphincterotomy
      (EPST) should be chosen. The removal of residual concrements with the Dormia
      basket through the external bile fistula gave positive results in 94.5% of cases.
      The effectiveness of EPST in removing the calculi without the external drain was
      86%. Reoperations were performed in 9.5% of the patients. Long-term results were
      followed up in all the patients during 5 years: good long-term results after non
      operable removal of the residual calculi through the external duct were from 92%
      during the first 3 years to 98% in the following 7-10 years.

PMID- 9915059
TI  - [Gunshot and blast injuries to the abdomen. The problems of mechanogenesis and of
      diagnostic and treatment procedures based on the experience of delivering
      surgical care to the wounded during the war in Afghanistan (1980-1989)].
AB  - The work is bases on an analysis of treatment of 2687 wounded in the abdomen.
      There are two main groups of factors in mechanogenesis of military injuries of
      the abdomen: ballistic parameters of gunshot shells and additional injuring
      factors of mine-explosive ammunition. Bullet wounds prevailed (60.2%), lethality
      from penetrating abdominal injuries was 31.4%. Laparotomies were performed in
      10.7% of the patients on the basis of absolute symptoms of penetrating wounds of
      the abdomen, in 74.1%--on the basis of analytical signs and in 15.2%--due to
      results of abdominal paracentesis. The following questions are discussed: the
      adequacy of the access, reinfusion of the blood accumulated in the abdominal
      cavity, surgical treatment for gunshot peritonitis, errors in treatment of
      wounded with abdominal injuries, application of new methods of treatment.
      Surgical features of traumatic disease and its treatment in wounded with gunshot
      abdominal injuries are described.

PMID- 9915060
TI  - [Peacetime gunshot wounds].
AB  - The article describes main principles of treatment of civilian gunshot wounds:
      rational organization of medical care to wounded at the prehospital stage,
      combination of diagnostic and medical process in specialized centers, early
      detection and eradication of menacing to life consequences of the wound, valuable
      intensive therapy at all stages of medical care and treatment, the shortest in
      time and full in volume specialized surgical care. Results of treatment of 507
      patients with gunshot injuries of different localization in the clinic of
      military surgery for the last 15 years show that during this period the amount of
      such patients rose from 6.4% to 12.2% of all patients with different injuries,
      slight wounds taking place in 30.8%, of mean gravity--in 7.1%, grave--in 46.4%,
      critically grave--in 14.9%. Lethality made up 17.2%, incidence of complications-
      31.2%, duration of hospital treatment was 33 +/- 1.8 days.

PMID- 9915061
TI  - [The features of the traumatogenesis and the ballistic characteristics of
      peacetime gunshot injuries].
AB  - Features of traumatogenesis and wound ballistics of civilian gunshot wounds are
      studied on the basis of the International Humanitarian Law and basic principles
      of wound ballistics. Data of 130 lethal cases and 260 wounded are presented.
      Types of the weapons used were taken into account. A detailed analysis of gunshot
      wounds inflicted by TT and PM handguns was made. The main components of
      traumatogenesis of civilian gunshot wounds were established.

PMID- 9915062
TI  - [The surgical procedure in blind gunshot wounds of the skull base].
AB  - Personal clinical observations during the recent years allow the authors to
      confirm the indisputable value of surgical experience got during the Great
      Patriotic War (1941-1945) and in particular, the "fourfold" scheme proposed by V.
      I. Voiachek for the diagnosis and treatment of blind gunshot wounds to the skull
      base. Computed tomography considerably increases the probability of detection of
      the exact localization of foreign bodies in complex anatomical structures of the
      skull and thus facilitates choosing the most rational surgical management. The
      use of the electro-optical transducer for the extraction of foreign bodies from
      almost inaccessible areas of the skull base decreases the risk of operation.

PMID- 9915063
TI  - [The characteristics of mine-blast wounds in shoals].
AB  - The data obtained in experiments on shoal using plastic charges of 100-50-25 g of
      equivalent power of antipersonnel mines showed that injuring action on shoal was
      four times greater than that on land and resulted in considerably graver skeletal
      traumas and distant injuries. Of special significance in pathogenesis of mine
      explosive wounds on shoal is pneumonia followed by arterial air embolism and
      encephalopathy. Although the undermining on land and on shoal have many common
      etiopathogenetic features, there are substantial differences first of all due to
      different mechanisms of their appearance. It must be taken into account while
      performing evacuatory, diagnostic and medical measures in such patients.

PMID- 9915064
TI  - [A topographic anatomical validation of the choice of the approach in
      reconstructive operations on the extracranial portion of the internal carotid
      artery].
AB  - The purpose of the research was to give a topographical substantiation of the
      choice of an approach to the extracranial internal carotid artery (ICA) in view
      of individual anatomical variability of ICA and various localizations of stenosis
      or occlusion. In 38 human corpses ICA was uncovered using operative methods
      proposed by Cooper. DePalma, Pauliukas and Nelson. A comparative estimation of
      the approaches was given with calculation of standard parameters of the operative
      wound. It was established that the approach to the subcranial ICA was dependent
      on the type of constitution, features of the anatomical shape of the mandible,
      distance between the mandibular angle and mastoid process. The statistical
      processing of the findings has shown that all the factors in question made up
      91.5% which is enough for the mathematical description of the position of ICA.
      Regression models of accessibility of the ICA segment for each of the four
      investigated approaches were made. The PC program for Windows 95/NT which allows
      the estimation of accessibility of ICA in each patient before operation was
      created. These mathematical models were used in the clinic for surgical treatment
      of the ICA pathology in 24 patients. The difference between the calculated data
      of ICA accessibility and intraoperative measurements was +/- 3 mm. It
      demonstrates reliability of the estimation of the approach parameters before
      operation.

PMID- 9915065
TI  - [The functional results of abdomino-anal resection of the rectum with the
      formation of a reservoir from the large intestine].
AB  - Under study were clinical and functional results of 27 patients aged 36 to 68
      years with adenocarcinoma (pT2-T3) of the ampullar part of the rectum who were
      submitted to abdomino-anal resection with the formation of J-shaped colonic
      reservoir. In the nearest postoperative period partial incompetence of the
      coloanal anastomosis, necrosis of the reservoir wall and its inflammation
      appeared in 4 patients. In 6 months after closure of the protective
      transversostomy full continence was noted in 24 patients. In 3 patients only
      there was a periodic incontinence of liquid stools and flatus. The formation of J
      shaped colonic reservoir in patients requiring the formation of low colorectal or
      coloanal anastomoses gives considerably better functional results of total
      resection of the rectum.

PMID- 9915066
TI  - [The current possibilities for plastic repair with axial skin flaps on the lower
      extremity].
AB  - Based on results of complex topographo-anatomical investigations in 187 lower
      extremities and experiences with performing 220 operations of free and non-free
      plasty with axial skin flaps formed in the femur, shin and foot, the authors
      consider the lower extremity as a donor site and a recipient field for such
      operations. Eight donor zones are selected on the lower extremity and 39
      different flaps can be formed within their limits, 27 of them being tested in the
      clinic. Comparative characteristics of all donor zones are given. The present-day
      possibilities of the substitution of different wound defects using the axial skin
      flaps from the femur, shin and foot are shown.

PMID- 9915067
TI  - [Frostbite as a problem for dermatoplastic surgery].
AB  - An analysis of the 35-years experiences with treatment of 621 patients with the
      IV-degree frostbite of hands and feet is presented. The surgical strategy of
      treatment of frostbite has undergone considerable evolution for these years. In
      addition to classical surgical treatment, the surgeons began to widely use
      methods of dermo-plastic surgery which allowed not only to save the maximum
      possible length of the extremity segment stump, but also to reduce the frequency
      of purulent complications and reamputations and thus to shorten the duration of
      hospital treatment.

PMID- 9915068
TI  - [The surgical treatment of cancer of the esophagus and cardia. The complications
      and hazards].
AB  - One-stage operations for carcinoma of the esophagus and cardia were performed on
      100 patients. The substitution of the resected esophagus was made with a
      isoperistaltic tube from the greater curvature of the stomach with anastomosis on
      the neck, in the pleural or abdominal cavities. Palliative interventions were
      fulfilled on 31 patients with inoperable carcinomas. An analysis of the structure
      and causes of postoperative complications and postoperative lethality has shown
      that among the most frequent causes of deaths in the postoperative period were
      purulent-infectious complications as a result of ischemia of gastric transplants
      and incompetence of sutures of the anastomoses as well as pleuro-pulmonary
      complications. Special attention was given to an analysis of complications after
      operations performed without thoracotomy from the cervico-abdominal access. The
      amount of postoperative complications was 30%, postoperative lethality 15%. One
      year survival after operations made up 57%, 3-year survival--less than 30%, 5
      year survival--less than 15%. Some recommendations are given for the surgical
      policy and methods of prophylactics of certain complications. Endolymphatic
      infusions of cytostatics used as adjuvant chemotherapy in complex treatment of
      patients with cardioesophageal carcinoma represent a perspective direction
      providing longer life of the patients without recidivations. From the oncological
      viewpoint the operation without thoracotomy are not always thought to be
      justifiable.

PMID- 9915069
TI  - [Radionuclide study in the diagnosis of infectious foci in heart surgery
      patients].
AB  - The radionuclide investigation was performed 1-3 and 24 hours after injection of
      a radiopharm preparation and included the single photon emission computed
      tomography of the heart and scintigraphy of the whole body. Inflammation foci
      were found on the scans as hyperfixation foci of autoleukocytes labeled with
      99mTc-HMPAO (hexamethylpropilene aminooxime). Four patients had abscesses with
      0.8-1.5 cm diameter in projection of the aortal and mitral valves of the heart,
      and in 10 patients there were foci of inflammation and suppuration of
      extracardiac localization (in the area of the operation wound, anterior
      mediastinum, frontal sinuses, transverse colon, parietal pleura). The data
      obtained convincingly speak of high sensitivity and specificity of radionuclide
      diagnostic methods with the help of labeled elements of the whole blood in
      recognizing latent inflammatory and suppurative processes in cardiosurgical
      patients at the pre- and postoperative periods.

PMID- 9915070
TI  - [Endolymphatic antibiotic therapy in the combined treatment of acute lung
      abscesses].
AB  - The concentration of antibiotics in the pulmonary tissue, regional lymph
      collectors was studied after direct and indirect endolymphatic infusions. The
      effectiveness of indirect endolymphatic antibiotic therapy is shown for treatment
      of purulent diseases of the lungs.

PMID- 9915071
TI  - [Long-term transbronchial catheterization of the destructive cavities in the
      treatment of acute lung abscesses with disordered bronchial patency].
AB  - High curative efficiency of prolonged transbronchial catheterization of
      destruction cavities of the lung is shown on the basis of results of treatment of
      80 patients. Possible risk factors and preventive measures in using this method
      are described.

PMID- 9915073
TI  - [Apparatus for artificial pulmonary ventilation and inhalation anesthesia].

PMID- 9915072
TI  - [Experience in using artificial pulmonary ventilation with an inverse ratio of
      the respiratory-cycle phases in acute lung injury in the victims of severe wounds
      and mechanical damages].
AB  - The possibility of using the methods of artificial pulmonary ventilation (APV)
      with positive pressure at the end of expiration (PPEE) and inverse ratio of the
      respiratory cycle phases for treatment of patients with grave wounds and
      mechanical injuries is assessed. PPEE is shown to have negative influence on gas
      exchange respiratory biomechanics and hemodynamics. The using of APV with
      inversed phases of the respiratory cycle allow to avoid the negative influence of
      APV on hemodynamics, improve the gas exchange and respiratory biomechanics
      indices as well as to reduce the amount of complications. The criteria are
      proposed showing when it is expedient to substitute the routine APV for the APV
      with inversed respiratory cycle phases.

PMID- 9915074
TI  - [The problems of ambulatory anesthesiology].
AB  - Prospects of the development of ambulatory anesthesiology are greatly dependent
      on understanding its problems caused by the specific character of work of the
      ambulatory polyclinical institutions. The most important of them is
      responsibility for safety of the patients during general anesthesia and after it
      as well as comfort feelings of the patients in the nearest postoperative period.
      The solution of these problems is related not only with qualification of
      anesthesiologists but also with the adequate, corresponding to the present-day
      level of the material technical supply of their work. Of special importance are
      the "postnarcosis" wards, ability of the personnel to evaluate the
      psychophysiological state of the patients and correspondence of their life
      conditions to the requirements of ambulatory anesthesiology.

PMID- 9915075
TI  - [The early diagnosis of postoperative infectious complications in heart surgery
      patients].
AB  - Great surgical aggression in operations on the heart and resulting
      immunodeficiency create prerequisites for the appearance and grave course of
      infectious complications. The authors have analyzed results of operative
      treatment of 100 patients with acquired valvular diseases. It has been
      established that low parameters of the resistance index of organism (RIO) before
      operation can be estimated as an unfavourable prognostic sign of the development
      of infectious complications. The RIO dynamics at the postoperative period in many
      aspects reflects the character of its course. RIO and the indices of the
      adaptation reaction show the degree of intoxication, make the clinical estimation
      objective, allow the assessment of efficiency of therapy and correction of
      medical prescriptions.

PMID- 9915076
TI  - [The combined use of intraoperative video endoscopy and contact microvascular
      dopplerography in the surgery of cerebral aneurysms].
AB  - The article describes results of an anatomo-clinical investigation using video
      endoscopy and contact microvascular dopplerography in surgery of cerebral
      aneurysms. The endoscopic anatomy of cisterns of the cerebral base was studied in
      36 corpses of adult humans. More than 200 video-endoscopic operative
      interventions were performed on sectional material. Video-endoscopy in
      combination with contact microvascular dopplerography was conducted in the clinic
      on 20 patients with aneurysms of the brain. Main advantages of endoscopy used in
      combination with microvascular dopplerography during clipping the aneurysm are
      formulated. Complex using the two methods described gives less volume of the
      access and traumaticity of the intervention but not less radical effect. It is a
      valuable and highly informative method which optimizes performing the operation
      and has less amount of postoperative complications.

PMID- 9915077
TI  - [The possibilities, realities and outlook for artificial enteral feeding in the
      surgical clinic].
AB  - The key problems are pointed out depending in their solution on the understanding
      by clinicians of different aspects of enteral artificial nutrition (EAN) as a
      variant of nutritional maintenance in practical surgery. These problems are:
      maintenance of performing EAN with the creation of the optimum nutrition tract;
      choice of the nutrition substrate sources for EAN; medicines accompanying EAN.
      The tasks of its maintenance are to provide the access to digestive tract, supply
      and equipment for EAN. The basic, actual and subsidiary variants of the
      nutritional maintenance are considered from the viewpoints of choosing means for
      EAN. Six classes of nutritional mixtures are described as means for the basic
      nutritional maintenance. Main directions for medicamentous support are presented:
      optimization of properties of the nutritional mixture and overcoming possible
      functional complications of EAN.

PMID- 9915078
TI  - [The surgical treatment of a large postoperative ventral hernia in patients over
      60].

PMID- 9915079
TI  - [The autoplasty of the abdominal wall in postoperative ventral hernias in middle
      aged and elderly subjects using N. I. Napalkov's modified method].

PMID- 9915080
TI  - [So we'll win?! (the view of a microbiologist on the problem of surgical
      infection)].

PMID- 9915081
TI  - [Brain death: the current status of the problem].

PMID- 9915082
TI  - [Surgeons--the presidents and commanders of the former Medical Surgical Academy-
      of the Military Medical Academy].

PMID- 9915083
TI  - Assuring the safe use of medications: the drug approval process and improving
      treatment decisions. Introduction.

PMID- 9915084
TI  - Overview of the US Food and Drug Administration's reform legislation.
AB  - This paper addresses the most commonly discussed issues regarding the US Food and
      Drug Administration Modernization Act. Particular emphasis is given to aspects
      that affect the pharmaceutical industry. It also discusses the agency's current
      efforts regarding implementation of specific provisions of the Act.

PMID- 9915085
TI  - Premarketing studies in the drug approval process: understanding their
      limitations regarding the assessment of drug safety.
AB  - This paper discusses the premarketing safety database that the US Food and Drug
      Administration receives from drug manufacturers. It reviews the kind of data we
      usually receive, what we do with the data, and how the data affect labeling. In
      addition, it discusses some of the limitations of that database in ensuring the
      safe use of medications.

PMID- 9915086
TI  - The US Food and Drug Administration Modernization Act of 1997: impact on
      consumers.
AB  - This paper provides a consumer's perspective on an important issue that has a
      profound impact on all of us: the US Food and Drug Administration (FDA)
      Modernization Act of 1997. In addition, it provides some background information
      on the National Consumers League, an organization that promotes consumer safety
      and protection with the FDA and its predecessors.

PMID- 9915087
TI  - Realizing the promise of the US Food and Drug Administration Modernization Act.
AB  - The Modernization Act of 1997 is the result of a partnership between the US Food
      and Drug Administration (FDA) and the pharmaceutical industry. Highlights of the
      Act, including agreements on user fees, timely review, pediatric studies, and
      national registry of clinical trials, are presented. Although progress has been
      made in each of these areas, this paper concerns the profound impact of
      combinatorial chemistry, genetic research, and pharmacoeconomics on the FDA, the
      industry, and the drug development process.

PMID- 9915088
TI  - Postmarketing drug surveillance: an epidemiologic approach.
AB  - Postmarketing surveillance refers to any means of gathering information about a
      product after it has been approved for public use. Postmarketing surveillance
      studies address assorted aspects of beneficial and detrimental adverse drug
      effects, including the existence of particular causal effects, frequency of and
      risk factors for certain outcomes, economic consequences of therapy, and
      characterization of drug use in clinical practice. The primary scientific
      discipline engaged in postmarketing studies is epidemiology. The principal
      epidemiologic study designs used in postmarketing surveillance studies are
      randomized trials, cohort studies, and case-control studies. Regardless of their
      design, all studies involving human subjects should be conducted by qualified
      investigators according to a written protocol that has been approved by an
      institutional review board. Promotional activities conducted under the guise of
      postmarketing studies are unacceptable.

PMID- 9915089
TI  - Limitations and strengths of spontaneous reports data.
AB  - US Food and Drug Administration (FDA) monitoring of the continued safety of
      marketed medical products depends greatly on spontaneous reporting of serious
      adverse events by health professionals. Despite its inherent limitations, the
      national postmarketing surveillance system provides vital information of clinical
      importance.

PMID- 9915090
TI  - Developing a uniform reporting system for preventable adverse drug events.
AB  - The United States Pharmacopeia (USP) Practitioners' Reporting Network utilized
      nearly three decades of experience to design and develop a nationwide, anonymous,
      Internet-accessible service for hospitals to report and benchmark medication
      errors (also known as "preventable adverse drug events"). As nationwide
      experiential reporting enters the 21st century, the features of MedMARx will
      provide facilities with the unprecedented ability to conduct daily continuous
      quality improvement that encompasses medication error risk analysis and
      prevention based on the experiences of other facilities. Data elements were
      developed based on review by expert panels and USP's experience with the
      Medication Errors Reporting Program. The success of this model could indicate its
      usefulness in other practice settings and for broader applications in health
      care.

PMID- 9915091
TI  - A process for interpreting data on adverse drug events: determining optimal
      target levels.
AB  - The Joint Commission on Accreditation of Healthcare Organizations (JCAHO)
      primarily accredits health care organizations against broad-based standards of
      performance. However, it has a role in postmarketing drug surveillance,
      specifically in terms of how health care organizations accredited by the Joint
      Commission review and respond to significant adverse drug events (ADEs) that
      occur in their organization. This paper discusses the role of the Joint
      Commission in reducing the incidence and severity of ADEs.

PMID- 9915092
TI  - Balancing risks versus benefits in drug therapy decisions.
AB  - The regulation of foods and drugs in the United States has repeatedly been
      increased in response to unjustified marketing claims or instances of dramatic
      harm from these substances. Because drugs are never safe or effective for
      everyone, the guiding principle for physicians should be to use pharmaceuticals
      in such a way as to maximize benefit and minimize harm.

PMID- 9915093
TI  - Role of evidence-based medicine and clinical practice guidelines in treatment
      decisions.
AB  - The Center for Practice and Technology Assessment (CPTA), which falls within the
      Agency for Health Care Policy and Research, was formed in 1997. By combining the
      Office of the Forum for Quality and Effectiveness in Health Care, which was
      responsible for the clinical practice guideline program, and the Center for
      Technology Assessment, CPTA was born. This paper discusses the roles of CPTA in
      the development of evidence-based medicine and clinical practice guidelines in
      treatment decisions.

PMID- 9915094
TI  - Regulation of prescription drug promotion: direct-to-consumer advertising.
AB  - The US Food and Drug Administration (FDA) is responsible for regulating the
      information on prescription drugs disseminated by sponsors to health care
      providers and consumers to ensure that it is truthful and not misleading, and
      that it presents a fair balance of benefit and risk information. Thus the public
      health is both protected and promoted by the dissemination of honest, accurate
      information about regulated products. This paper discusses the regulatory
      requirements for promotional materials for prescription drugs and the standards
      used by the FDA to evaluate these materials. It also discusses the agency's views
      on direct-to-consumer advertising, the enforcement actions that are available to
      the FDA, the process used by the FDA to determine what action should be taken and
      when, and what remedies are available.

PMID- 9915095
TI  - Direct-to-consumer promotion: an industry perspective.
AB  - Direct-to-consumer (DTC) advertising of prescription medicines is an important
      trend in health care delivery. Many questions must be answered as we move
      forward, and more research is needed. However, DTC advertising has enormous
      potential benefit for consumers.

PMID- 9915096
TI  - Direct-to-consumer advertising: a pharmacy perspective.
AB  - This paper explains the current policies of the American Pharmaceutical
      Association (APhA) and other national organizations on direct-to-consumer (DTC)
      advertising, reviews the findings of a survey on DTC advertising conducted by the
      APhA and Prevention Magazine, and identifies key issues for DTC policy
      development.

PMID- 9915097
TI  - Prescription to over-the-counter switch: a regulatory perspective.
AB  - This paper discusses the origins of the over-the-counter (OTC) drug category and
      presents information about the process of switching a drug from prescription (Rx)
      to OTC status. It also reviews past and current drug laws in terms of how they
      relate to OTC drugs.

PMID- 9915098
TI  - Prescription to over-the-counter switches: the physician perspective.
AB  - Changes in a drug's availability from prescription only to over-the-counter (OTC)
      status is of concern to physicians from both public health and individual patient
      perspectives. While acknowledging the potential benefits of these switches, the
      author notes important caveats, including the need for scientifically derived
      pediatric dosages; information in the medical record regarding OTC use that
      allows cohesive monitoring; clarity and precision in labeling for consumers; and
      continued coverage of such drugs for medically indigent patient populations.
      Current actions by physician organizations are noted.

PMID- 9915099
TI  - American Pharmaceutical Association review of literature on prescription to over
      the-counter drug switches.
AB  - Research was conducted by staff of the American Pharmaceutical Association
      (APhA), the national professional society of pharmacists, to inform the APhA
      policy process. Findings indicate that many consumers view products that were
      switched from prescription to over-the-counter (OTC) status as being more
      effective than products that have not previously been designated as prescription
      drugs, and they prefer to purchase switched products. Consumer purchases of
      switched products replace utilization of prescription drugs, physician visits,
      and laboratory services, but no data were found concerning increased utilization
      that may eventually result from foregone or delayed medical attention. Evidence
      exists that many comparatively well-informed consumers are knowingly using these
      products in a manner inconsistent with their labeling, and are using
      complementary and alternative medications for which labeling is uninformative in
      lieu of either prescription or OTC products. A need exists for more and better
      quality pharmaceutical care services from pharmacists to support informed self
      care decision making by consumers.

PMID- 9915100
TI  - Evolution of self-care with over-the-counter medications.
AB  - Self-care with over-the-counter (OTC) medicines has evolved from the "dark ages"
      of patent medicine manufacture and sale to a modern era of new drug development
      involving prescription-to-OTC switch. This evolution is largely due to the OTC
      Review, which placed science at the cornerstone of safety, effectiveness, and
      labeling of nonprescription medicines. As self-care with OTC drugs has evolved,
      the switching of drugs from prescription to nonprescription status has produced
      important benefits, creating more self-reliant consumers through novel self-care
      therapeutics, significant cost savings to the health care system, expanded
      markets for companies, enhanced science for regulatory decisions, a more consumer
      friendly label for all OTC agents, and a more consistent and predictable drug
      approval process. Potential regulatory barriers and an evolving claims
      environment for prescription drugs and dietary supplements present important
      challenges for the OTC industry today.

PMID- 9915101
TI  - T cell hypofunctions and glomerular sclerotic and angiogenic changes found both
      in rats received unilateral nephrectomy plus transplantation of syngeneic
      mesenteric lymph nodes and in rats received unilateral nephrectomy plus
      splenectomy.
AB  - Five male and 7 female Lewis rats unilaterally nephrectomized at the ages of 44
      46 days were transplanted with the mesenteric lymph nodes (MLN) obtained from
      syngeneic rats 4 months after the nephrectomy. In addition, 6 males received
      unilateral nephrectomy plus splenectomy at the age of 38 days. All of these rats
      were observed for 8.5 months after the nephrectomy. Flow cytometry analyses
      indicated that 17-32% of MLN lymphocytes and 4-20% of peripheral blood (PB)
      lymphocytes lost CD2 antigen in the unilaterally nephrectomized rats.
      Approximately 20% of PB and MLN lymphocytes had lost CD2 antigen in the males
      with combined splenectomy and nephrectomy, one of which died of severe infection.
      The survival rates of the MLN graft after 4.5 months were 100% in the 5
      nephrectomized males and 14% in the 7 nephrectomized females. The CD2 antigen on
      immunologically activated T cells was up-regulated. Twenty-eight% lymphocytes of
      the survived MLN graft and 51% PB T cells of the 7 females with MLN graft
      rejection showed the CD2 up-regulation. It was shown immunohistochemically that
      not only CD2-positive (+) cells but also CD4+ cells were increased in the cortex
      of the survived MLN graft. The hepatocyte growth factor receptor gene, c-met
      gene, was shown to be present in lymphocytes. The c-met was considered to
      cooperate with the CD2. Interstitial mononuclear cell infiltrations with
      glomerulosclerosis were found in the remaining kidneys of the males with
      unilateral nephrectomy plus MLN grafts. Glomerular angiogenesis and accompanying
      endothelial cell apoptosis were demonstrated without mesangial cell proliferation
      in the males with unilateral nephrectomy plus splenectomy.

PMID- 9915102
TI  - Failure in detection of Epstein-Barr virus and cytomegalovirus in specimen
      obtained by fine needle aspiration biopsy of thyroid in patients with subacute
      thyroiditis.
AB  - To study the possible role of viral infection in the etiology of subacute
      thyroiditis (SAT), we measured serum virus-specific antibodies to measles,
      rubella, mumps, type I herpes, chicken pox, human parvovirus B19 and
      cytomegalovirus (CMV) in 10 patients with SAT during the course of illness. In
      spite of the presence of IgG to each virus in more than 70% of patients, no
      significant changes in the IgG titers were observed except those to measles,
      rubella, chicken pox or CMV in only 10% of patients, respectively. Then we
      examined the presence of virus DNA in specimens of 9 patients with SAT obtained
      by fine-needle aspiration biopsy (FNAB) of the thyroid. DNA was amplified to
      detect that of Epstein-Barr virus and CMV by polymerase chain reaction. However,
      none of them were detected in all the specimens. Whereas previous studies suggest
      the involvement of viral infection in the pathogenesis of SAT, we failed to
      demonstrate significant changes in serum antiviral antibody titers or to detect
      viral DNA in the specimens obtained by FNAB of the thyroid. Thus further studies
      are clearly required to establish the definite role of viral infection in the
      pathogenesis of SAT.

PMID- 9915103
TI  - Transient decrease in skin resistance response and level at the deh-chi stage
      caused by manual acupuncture.
AB  - Deh-chi is described as a kind of soreness, numbness, or heavy swelling in deep
      tissues during manual acupuncture. This finding is important in acupuncture
      therapy, although the mechanism of this phenomenon remains unclear. Skin
      resistance response (SRR) and skin resistance level (SRL) are expressed as a
      component of alternating current and direct current changes in electrodermal
      activity (EDA) respectively. In the present study, we recorded SRR and SRL, skin
      blood flow and perspiration simultaneously in an attempt to determine the
      relationship between skin sympathetic nerve activity and EDA at the deh-chi
      stage. We found that SRR, SRL and skin blood flow decrease, and that perspiration
      increases transiently at the deh-chi stage. Our findings indicate that manual
      acupuncture causes an increase in vasomotor and sudomotor activities, a decrease
      in skin blood flow, and increased perspiration. These SRR and SRL recordings may
      be taken as an indicator of deh-chi.

PMID- 9915104
TI  - Surgical indications for neonatal ovarian cysts.
AB  - Ante- or neonatal ovarian cysts can be often diagnosed by routine
      ultrasonography. Small simple ovarian cysts, which can be followed with serial
      ultrasonography, usually resolve spontaneously. Large simple cysts and
      complicated cysts should undergo surgical treatment to reduce the potential for
      serious complications. Seventeen ovarian cysts were experienced between 1983 and
      1997. Sixteen cases underwent surgical treatment at less than 1 month of age
      according to our protocols. In this report, we reviewed these cases for clinical
      presentation, ultrasound data, management, intraoperative findings,
      complications, and outcome. At operation, nine of them showed torsion, and seven
      of them showed necrotic changes. Only five of them was considered to fall into
      torsion by preoperative ultrasonography. In five cases whose blood flow could not
      improve after reduction of torsion, salpingo-oophorectomy was performed. We
      consider that small simple ovarian cysts under 4 cm in diameter can be observed
      carefully with serial ultrasonography. But, not only complicated ovarian cysts
      and simple cysts over 5 cm in diameter, but smaller cysts showing no decrease in
      size should be considered for surgical indication to rescue the ovarian tissue.

PMID- 9915105
TI  - Prevalence of chronic fatigue syndrome in a community population in Japan.
AB  - In order to know the prevalence of chronic fatigue syndrome (CFS) in a community
      population in Japan, we analyzed data from a population-based interview survey.
      Two cases out of 137 respondents experienced chronic fatigue during a period of
      nine months, suffered from 50% or more reduction of daily activity due to fatigue
      and had no other physical or psychiatric diagnosis. Both of the two cases
      fulfilled the 1994 Centers for Disease Control (CDC) criteria and the British
      criteria. The point and nine-month prevalence rates of CFS were both 1.5% (95%
      confidence intervals, 0.4-5.2%). None fulfilled the 1989 CDC criteria for CFS.
      The prevalence rate of CFS was higher than those in previous studies in the
      Western countries, suggesting a need for future research on cross-cultural
      differences in the definition, prevalence and symptomatology of CFS.

PMID- 9915106
TI  - Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH
      in healthy volunteers.
AB  - In this study, we examined the effect of rabeprazole (E3810), a novel proton pump
      inhibitor, on gastric acidity under physiological conditions in healthy
      volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour
      intragastric pH monitoring was performed three times to seven subjects randomly
      assigned in a cross over fashion to one of the following groups; without drug
      administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The
      median pH for 24 hours was 2.15 in the basal study, while the corresponding
      median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole,
      respectively. Significant differences in the median pH were observed between the
      basal study and that after administration of the 10 mg and 20 mg doses of
      rabeprazole. The cumulative percentage of pH readings above the threshold pH 4
      value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10
      mg and 20 mg doses of rabeprazole, respectively. This result indicates that the
      efficacy of rabeprazole allows for substantial control of gastric acidity with
      once-daily dosing, and that both the 10 mg and 20 mg doses result in potent
      inhibition of gastric acid secretion.

PMID- 9915107
TI  - A case of basal cell adenocarcinoma of the parotid gland.
AB  - We present a 73-year-old female with an enlarged mass in the right parotid gland.
      Fine-needle aspiration cytology suggested pleomorphic adenoma. Diagnostic imaging
      revealed that the tumour had a well-defined margin arising from the deep lobe of
      the parotid gland. A total parotidectomy with preservation of the facial nerve
      was performed. The final histopathological diagnosis including
      immunohistochemical studies was basal cell adenocarcinoma, which is a recently
      defined entity and a rare epithelial neoplasm. No sign of local recurrence or
      metastasis 24 months postoperatively has been observed.

PMID- 9915108
TI  - Efficacy of long-term sulfamethoxazole-trimethoprim therapy in a boy with
      hyperimmunoglobulin E syndrome.
AB  - A boy with hyperimmunoglobulin E syndrome (HIE syndrome), who was successfully
      treated with long-term sulfamethoxazole-trimethoprim (SMX-TMP) is reported. He
      had been suffering from recurrent pruritic dermatitis soon after birth and had a
      significant high level of serum immunoglobulin E. Although an initiation of SMX
      TMP therapy resulted in resolution of his clinical manifestations, cessation of
      the treatment exacerbated the symptoms. Chemoprophylaxis of other oral
      antibiotics, which were suitable for Staphylococcus aureus isolated from lesions
      of the patient were unsuccessful. Another trial of low-dose SMX-TMP therapy
      resulted in gradual subsidence of the clinical manifestations. From these
      observations, efficacy of SMX-TMP therapy to prevent bacterial infection in the
      patient is clinically apparent. Although precise mechanism of the therapy remains
      speculative, long-term SMX-TMP therapy might be of benefit and low clinical
      toxicity in HIE syndrome.

PMID- 9915109
TI  - Specificity of 4'''-acetylation by an aminoglycoside-modifying enzyme in
      arbekacin-resistant strains of methicillin-resistant Staphylococcus aureus.
AB  - Four arbekacin (ABK)-resistant clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA) were studied regarding their mechanism of
      aminoglycoside-resistance. Metabolites of amikacin (AMK) and gentamicin(GM) were
      obtained by reaction with excess amounts of crude enzyme preparation extracted
      from the ABK-resistant MRSA strains. Then the metabolites were then isolated and
      analyzed by means of 1H, 13C-nuclear magnetic resonance. The AMK-modification was
      4'''-N-acetylation. However, the site of GM-acetylation may be 6'-N-position by
      these strains.

PMID- 9915110
TI  - A new method to improve olfactory responses to GC effluents.
AB  - Biological detectors such as the human nose or an insect antenna represent
      extremely attractive detectors for gas chromatography (GC) since they are
      specifically tuned to perceive biologically relevant compounds. However, these
      detectors are nonlinear, noisy and often perform poorly under standard GC
      conditions since they are adapted to detect transient rather than long-lasting
      stimuli. These drawbacks can be overcome if the chemical stimulus, delivered by
      the gas chromatograph, is re-shaped (modulated) before reaching the biological
      detector. We describe a pulsing system that improves the performance of an insect
      olfactory system when stimulated with the effluent from a GC capillary column.
      Chemicals eluted from the GC column are trapped and rapidly desorbed within a
      thermal modulator in order to transform the continuous effluent into a succession
      of short-pulsed stimuli. The output from this modulator was directed to an insect
      antenna, from which electrophysiological responses were recorded. The system was
      evaluated with adult male Spodoptera littoralis (Lepidoptera: Noctuidae)
      stimulated with the conspecific female sex pheromone. Results obtained with this
      new approach indicate that both sensitivity and reliability of the biological
      detector are improved compared with the classical technique. Possible
      developments of this new technique are discussed.

PMID- 9915111
TI  - The characteristics of the electrovomeronasogram: its loss following vomeronasal
      axotomy in the garter snake.
AB  - Electrovomeronasogram (EVG) recordings were made from adult garter snakes,
      Thamnophis sirtalis. Stimulation of vomeronasal epithelium with a stimulus
      prepared from prey, earthworm electric shock secretion (ESS), evoked EVG response
      in a dose-dependent manner. The magnitude of the EVG response to ESS was
      remarkably larger than n-amyl acetate and glutamate, which elicited insignificant
      responses, supporting the idea that the vomeronasal system is differentially
      sensitive to liquid delivery of biologically significant chemical stimuli.
      Fourteen days following vomeronasal axotomy, the magnitudes of the EVG responses
      of animals which received bilateral axotomy without cauterization or with
      cauterization was -0.19+/-0.07 mV or -0.05+/-0.02 mV respectively, compared with
      the normal EVG response of -0.41+/-0.10 mV. The epithelia of animals which
      received bilateral axotomy without cauterization exhibited remarkable
      degeneration of the bipolar neurons. Maximal depletion of bipolar neurons
      occurred in the epithelia denervated with cauterization, though the difference
      between cell densities in vomeronasal neuron layers in these epithelia was not
      statistically significant. The present results clearly indicate that the fewer
      neurons the epithelium contains, the smaller EVG response it generates,
      suggesting that the receptor neurons are the primary origin of EVG responses.

PMID- 9915112
TI  - Effects of chorda tympani nerve anesthesia on taste responses in the NST.
AB  - Human clinical and psychophysical observations suggest that the taste system is
      able to compensate for losses in peripheral nerve input, since patients do not
      commonly report decrements in whole mouth taste following chorda tympani nerve
      damage or anesthesia. Indeed, neurophysiological data from the rat nucleus of the
      solitary tract (NST) suggests that a release of inhibition (disinhibition) may
      occur centrally following chorda tympani nerve anesthesia. Our purpose was to
      study this possibility further. We recorded from 59 multi- and single-unit taste
      responsive sites in the rat NST before, during and after recovery from chorda
      tympani nerve anesthesia. During anesthesia, average anterior tongue responses
      were eliminated but no compensatory increases in palatal or posterior tongue
      responses were observed. However, six individual sites displayed increased taste
      responsiveness during anesthesia. The average increase was 32.9%. Therefore,
      disinhibition of taste responses was observed, but infrequently and to a small
      degree in the NST At a subset of sites, chorda tympani-mediated responses
      decreased while greater superficial petrosal-mediated responses remained the same
      during anesthesia. Since this effect was accompanied by a decrease in spontaneous
      activity, we propose that taste compensation may result in part by a change in
      signal-to-noise ratio at a subset of sites.

PMID- 9915113
TI  - The taste of polycose in hamsters.
AB  - Hamsters show a preference for Polycose, a mixture of starch-derived glucose
      polymers, that is as strong as their preference for sucrose. However, in the
      hamster, taste aversions to Polycose may be less easily acquired than taste
      aversions to sucrose and the qualitative aspects of Polycose are unknown in this
      species. In order to examine the taste of Polycose in the hamster, we utilized a
      taste-aversion protocol with two conditioning trials. Animals were trained to
      avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose
      and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were
      conditioned with deionized water. After the second conditioning trial,
      generalization testing began for the three conditioning stimuli plus 3 mM citric
      acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose,
      sucrose or the Polycose/sucrose mixture cross-generalized, demonstrating that
      Polycose and sucrose share a common taste percept in the hamster. None of the
      aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among
      the patterns of taste generalizations indicated that the tastes of Polycose and
      sucrose also had distinct qualitative components. Finally, although the taste of
      100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of
      sucrose could still be detected in a mixture with Polycose.

PMID- 9915114
TI  - Effects of GABA on acutely isolated neurons from the gustatory zone of the rat
      nucleus of the solitary tract.
AB  - Responses of acutely isolated neurons from the rostral nucleus of the solitary
      tract (rNST) to GABA receptor agonists and antagonists were investigated using
      whole-cell recording in current clamp mode. The isolated neurons retain their
      morphology and can be divided into multipolar, elongate and ovoid cell types.
      Most rNST neurons (97%), including all three cell types, respond to GABA with
      membrane hyperpolarization and a reduction in input resistance. The GABA(A)
      receptor agonist muscimol reduces neuronal input resistance in a concentration
      dependent manner, whereas the GABA(B) receptor agonist baclofen had no effect on
      any of the neurons tested. The GABA and muscimol reversal potentials were both
      found to be -75 mV Both the GABA competitive antagonist picrotoxin and the
      GABA(A) receptor antagonist bicuculline block the effect of GABA in a
      concentration-dependent manner. These results suggest that GABA activates all
      neurons in the rNST and that inhibitory synaptic activity is important in
      brainstem processing of gustatory and somatosensory information.

PMID- 9915115
TI  - Amino acid sequence, post-translational modifications, binding and labelling of
      porcine odorant-binding protein.
AB  - An odorant-binding protein, migrating in SDS-PAGE with an apparent molecular
      weight of 22 kDa and an isoelectric point of 4.2, has been purified from pig
      nasal mucosa. Its complete amino acid sequence was determined by a combination of
      mass spectrometry and Edman degradation procedures. The protein consists of a
      single polypeptide chain of 157 amino acids, presenting at the N-terminus a
      pyroglutamic acid residue. The two cysteine residues, occurring in the primary
      structure at positions 63 and 155, are involved in an intramolecular disulphide
      bridge. Sequence comparison with other lipocalins revealed a good similarity with
      bovine odorant-binding protein, the only member of this class which does not
      contain disulphide bonds and of which the three-dimensional structure recently
      has been resolved. Nine out of the 1 6 residues lining the binding pocket in
      bovine OBP are conserved in the porcine protein, suggesting structural
      similarities in this region of the molecule. The synthesis of a fluorescent
      photoaffinity labelling agent and of two tin-containing thymol analogues is also
      described. These compounds together with other ligands were able to bind the
      protein as revealed by competitive binding experiments.

PMID- 9915116
TI  - Gustatory responses to amino acids in the chorda tympani nerve of C3H mice.
AB  - Integrated neural responses to various amino acids were recorded from the chorda
      tympani (facial) nerve in C3H mice. The basic amino acids hydrochlorides L-Arg
      HCl and L-Lys-HCl evoked large magnitude integrated taste responses, similar to
      that for NaCl, and had estimated electrophysiological thresholds of 0.0001 M. No
      significant difference was indicated between the response magnitudes for the L-
      and D-forms of the basic amino acid hydrochlorides; however, responses to the
      basic amino acid hydrochlorides cross-adapted with NaCl. Responses to neutral L
      amino acids (Ser, Ala, Gly), which taste sweet to humans, showed higher
      thresholds (>0.0003 M), similar to that for sucrose, and did not cross-adapt with
      basic amino acid hydrochlorides or with NaCl. Responses to the neutral amino
      acids L-Ser and L-Ala were larger than those to their D-amino acid enantiomers.
      The acidic amino acids L-Asp and L-Glu showed concentration-response functions
      different from that for HCl. Both acidic amino acids were more stimulatory than
      HCl at the same pH, although the responses to them were cross-adapted by HCl,
      indicating a pH effect. A comparison of the stimulatory effectiveness among amino
      acid derivatives and analogues suggested that the alpha-amino group is essential
      for the stimulatory effectiveness of neutral amino acids.

PMID- 9915117
TI  - A novel monoclonal antibody that recognizes apical membrane of frog taste cells.
AB  - We established a hybridoma clone 1N1 that produced a monoclonal antibody to stain
      the apical portion of frog taste cells, by directly immunizing taste discs of the
      bullfrog (Rana catesbeiana) without any dispersion procedure of the taste organ.
      The antibody stained discrete regions on the surface of the taste discs, but did
      not stain the epithelium sheet of the tongue devoid of taste discs. The antibody
      stained approximately 93% of the taste discs tested (172/184) derived from nine
      frogs, showing that distribution of the antigen was common to most of the taste
      discs. The following observations strongly suggested that the antibody recognized
      a certain antigen on the apical membrane of the taste cells. (i) The antibody
      selectively stained cross points of intermucus areas on the surface of the taste
      disc. Neither the mucus cells nor the wing cells that mainly cover the surface
      were stained with the antibody. (ii) Dispersed taste cells were prepared by
      calcium ion chelating and subsequently by collagenase treatment to avoid
      digestion of the antigen. The antibody stained the apical end of the taste cells.

PMID- 9915118
TI  - Unilateral naris occlusion and the rat accessory olfactory bulb.
AB  - Blocking airflow through half of the nasal cavity during early life results in a
      25% reduction in the size of the ipsilateral main olfactory bulb. The present
      study indicates that the size of the accessory bulb is relatively unaffected by
      the procedure.

PMID- 9915119
TI  - AChemS: the beginning. Association for Chemoreception Sciences.
AB  - This paper unfolds the events, the people and the times that led up to the
      founding of AChemS and fashioned its character during its early formative years.
      It describes the path over which AChemS came, going from the original assertions
      and denials for the need of such an organization to its later inception and
      nascent development. This narration highlights such topics as the debate over the
      need for AChemS, the role of National Science Foundation in the founding of
      AChemS, the derivation of the Association's name, the choice of Sarasota and the
      Hyatt House as the meeting site, the generation of the programs for the early
      annual meetings, the adoption of the bylaws, the process of incorporation and tax
      deferment, and the birth of the Givaudan Lectureship. Most emphatically
      highlighted, however, is the enthusiasm, commitment and hard work that the
      members of the chemosensory research community displayed in bringing AChemS to
      fruition.

PMID- 9915120
TI  - The timing of alpha-gustducin expression during cell renewal in rat vallate taste
      buds.
AB  - The G protein subunit alpha-gustducin is expressed in a subset of light (Type II)
      but not in dark (Type I) cells in rat vallate taste buds. The thymidine analogue
      5-bromo-2'-deoxyuridine (BrdU) is incorporated into DNA during the S-phase of the
      cell cycle and can be used to determine the time of origin of a cell. In this
      study, 31 rats were injected with BrdU (50 mg/kg i.p.) and perfused at various
      times, from 2.5 to 10.5 days, following BrdU administration. Vallate papillae
      were embedded in polyester wax, cut into 4 microm transverse sections, and
      characterized with antibodies to BrdU and alpha-gustducin. Sections were
      processed for indirect immunofluorescence or with an immunoperoxidase procedure.
      From immunoperoxidase material on 21 rats, counts of alpha-gustducin- and BrdU
      labeled cells were obtained from 300-800 taste bud profiles at each survival
      time; a total of 4122 taste bud profiles were examined. Cells with nuclei
      immunoreactive for BrdU occurred within the taste buds at 2.5 days and double
      labeled cells were clearly evident at 3.5 days; a small number of double-labeled
      cells were seen as early as 2.5 days. Double-labeled cells reached a peak at 6.5
      days and did not decline significantly by 10.5 days. Cells labeled for BrdU but
      not alpha-gustducin peaked at 5.5 days and showed a significant decline by 8.5
      days. These latter cells included light cells not expressing alpha-gustducin and
      dark cells, which have previously been shown to have a shorter life span than
      light cells. These data suggest that expression of alpha-gustducin appears very
      early in a cell's life span and that these cells are longer lived than many of
      the cells that do not express this G protein.

PMID- 9915121
TI  - Anatomical description of a new organ in the nose of domesticated animals by
      Ludvig Jacobson (1813).

PMID- 9915122
TI  - Trigeminal chemosensitivity: Differences in relation to the time of the day.
AB  - Day-night differences of trigeminal chemosensitivity were investigated in 18
      healthy volunteers employing both pain-related cortical potentials and pain
      ratings in response to stimulation of the nasal mucosa with CO2. Day-night
      differences were found with N 1 P2 amplitudes, P2 latencies and pain ratings. It
      is concluded that the time of the day must not be ignored when human
      chemosensitivity is investigated at suprathreshold levels.

PMID- 9915123
TI  - Coexistence of glutamate and acetylcholine in the developing motoneurons.
AB  - Glutamate receptors mediate excitatory neurotransmission in the central nervous
      systems and are important in neuronal development, acquisition of memory, and are
      related to some neurodegenerative disorders. In the current study, co-cultures of
      spinal neurons and myotomal muscle cells were prepared from 1-day-old Xenopus
      embryo. Spontaneous synaptic currents were recorded from innervated myocytes
      using whole-cell recording. Local perfusion of glutamate receptor agonists, N
      methyl-D-aspartate (NMDA) and non-NMDA, at synaptic regions with another
      micropipette all increased the frequency of spontaneous synaptic currents. Whole
      cell recording was also made in the nerve growth cone of cultured spinal neurons.
      Local application of glutamate, NMDA or kainate all induced an inward current,
      indicating the coexistence of NMDA and non-NMDA receptors in the nerve terminals
      of developing motoneurons. Some innervated myocytes contracted spontaneously in
      the cultures, which were processed for glutamate immunocytochemistry after the
      recording of spontaneous synaptic currents. Glutamate immunoreactivity appeared
      in neuronal varicosities and neuromuscular junctions, indicating that glutamate
      is co-stored with acetylcholine in motoneurons. Double staining for glutamate and
      choline acetyltransferase further provides the evidence of the colocalization of
      glutamate and acetylcholine in developing motoneurons. These results suggest that
      both NMDA and non-NMDA receptors exist in the nerve terminals of developing
      motoneurons. Furthermore, glutamate and acetylcholine coexist in the motoneurons.
      The presynaptic glutamate receptors may thus have a physiological role in
      neuromuscular synaptogenesis in early embryonic stages.

PMID- 9915124
TI  - Transient frequency and intensity sensitivities of central auditory neurons
      determined with sweep tone.
AB  - To determine the transient frequency and intensity sensitivities of central
      auditory neurons, we implemented an exponential sweep tone stimulus (2 sec in
      period, mean sweep rate 3.3 octave/sec), intensity of which varied systematically
      across trials. Response of single units to the stimulus was studied at the
      inferior colliculus (IC) of urethane-anesthetized rats. Most IC units responded
      to the sweep tone by one or more transient increases in discharge rate. The area
      of increased discharge, or response area (RA), was delineated on the frequency
      intensity plane. The tip of RA gives the best frequency (BF) and minimum
      threshold (MT) of the cell. We also compared the BF and MT concurrently obtained
      with another method, viz., the conventional 'audio-visual' method of subjective
      judgment. Results showed that for the same population of cells (n=130),
      correlation between the two methods is better for BF (r=0.91) than for MT
      (r=0.78). Such discrepancy was discussed in relation to the response
      characteristics of these central auditory neurons.

PMID- 9915125
TI  - The role of the inhibitory nonadrenergic noncholinergic system in antigen-induced
      pulmonary hypersensitivity.
AB  - To study the role of the inhibitory nonadrenergic noncholinergic (i-NANC) system
      in regulating bronchial reactivity during antigen challenge, we first tested a
      blocker of the i-NANC system (oxyhemoglobin, HbO2, 2.5 microm) on the relaxation
      response of guinea pig tracheal strips (n=6) in vitro to electrical field
      stimulation (ES) in the presence of atropine (1 microg/ml) and propranolol (2
      microg/ml). Fresh HbO2 significantly inhibited 35.3+/-4.5% (P<0.001) of the NANC
      relaxation response. Secondary, 26 anesthetized, ovalbumin-sensitized animals
      were divided into three groups: antigen challenged (n=10), pretreated with HbO2
      (13 mg/kg) and challenged (n=9), and treated with HbO2 only (n=7). Pulmonary
      resistance (RL) and dynamic compliance (Cdyn) were measured 15-20 min prior to
      (baseline) and up to 30 min after antigen or HbO2 injection. Antigen challenge
      alone induced early maximal respiratory changes: RL increased 1646+/-115% above
      baseline (2 min) whereas Cdyn decreased 42+/-10% below baseline (4 min). These
      changes returned to baseline within 15 min. Pretreatment with HbO2 increased peak
      respiratory responses induced by antigen [RL, 3728+/-1680% above baseline; Cdyn,
      69+/-7% below baseline (P<0.05)]. HbO2 delayed significantly (P<0.05) the time
      for recovery of RL and Cdyn. HbO2 alone had little effect on respiratory
      parameters. We conclude that HbO2 may antagonize the i-NANC system in the airway
      and this antagonism may accentuate pulmonary hypersensitivity during acute
      antigen challenge.

PMID- 9915126
TI  - Characteristics of spontaneous Ca2+ oscillations in bovine aortic endothelial
      cells in Ca2+-free solution.
AB  - In nominally Ca2+-free solution, the incidence of spontaneous Ca2+ oscillations
      in the cultured bovine aortic endothelial (BAE) cells may occur during
      superfusion. Application of 3 microM ATP induced a single Ca2+ transient
      regardless of the prior absence or presence of spontaneous oscillations. The
      total mobilized [Ca2+] depends on the incidence of spontaneous oscillations and
      the length of exposure in Ca2+-free solution. The maximal rate of rise of the
      transient in cells induced by ATP immediately after an spontaneous spike was
      greater than that in cells without any spontaneous activity. But there was no
      difference in the recovery time constant. The sum of areas of spontaneous and ATP
      induced transients in cells with spontaneous activity was not different from that
      of ATP-induced transient in cells without spontaneous activity. The results
      suggest that BAE cells, after growth to confluence, are subjected to spontaneous
      oscillations during superfusion in Ca2+-free solution. The release of internal
      Ca2+ in response to ATP is enhanced in cells with spontaneous oscillations. The
      content of ATP-sensitive stores continually decreased when cells were superfused
      with Ca2+-free solution, and most of the spontaneous release of Ca2+ was lost and
      not sequestrated back into ATP-sensitive stores.

PMID- 9915129
TI  - The effect of trigeminal neurotomy on the alteration of local cerebral blood flow
      of normotensive and hypertensive rats in acute cold stress.
AB  - The cold season is reported to have the highest incidence of stroke in a year.
      Cold is usually detected by cold receptors in the face. The present studies were
      designed to test whether the trigeminal nerve plays a role in the regulation of
      local cerebral blood flow (LCBF) in animals exposed to a cold environment. Since
      hypertension affects the incidence of strokes, both Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) were used. Each species was divided into
      four groups: trigeminal neurotomy (TNx) or control group at room temperature (20
      degrees C) or cold environment (5 degrees C), respectively. LCBF in 14 brain
      structures was measured using the [14C] iodoantipyrine technique and tissue
      dissecting methods. Our results show that TNx did not alter physiological
      parameters and LCBFs in WKY and SHR kept either at 20 degrees C or at 5 degrees C
      for 30 min. However, a transient exposure (30 minutes) to cold caused
      concomitantly a significant decrease in core body temperature of both WKY and SHR
      groups (p<0.05, Student's paired t-test) and a significant decrease in LCBFs at
      the temporal cortex (TC), hypothalamus (HYP) and midbrain (MID) of WKY and TC of
      SHR (P<0.05, MANOVA). TNx did not alter LCBFs significantly following transient
      cold exposure in WKY and SHR. Our findings indicate that in the cold environment,
      the lowered LCBFs in some areas of the brain may relate to the decreased
      metabolic rate caused by decreased body temperature, and may partly contribute to
      the higher prevalence of stroke in winter. Our findings also suggest that
      trigeminal nerve do not exert tonic control of LCBFs and the cold afferents in
      trigeminal nerve are not important in modulation of the LCBFs.

PMID- 9915128
TI  - Effects of chronic exercise on muscarinic receptor-mediated vasodilation in rats.
AB  - Previous studies have demonstrated that vascular responses to acetylcholine
      (ACh), an endothelium-dependent vasodilator, are enhanced in exercise-trained
      animals. In order to see if chronic exercise upregulates endothelial muscarinic
      (M) receptor, the subtype of M receptors responsible for ACh-induced
      vasorelaxation in the thoracic aorta of male Wistar rats was characterized first,
      then a receptor assay was performed. These animals were divided into exercise and
      control groups. The trained rats ran on a treadmill with a moderate intensity for
      60 min per day, 5 days per week. After 10 weeks of training, rats were
      decapitated and their thoracic aortae were isolated. The subclass of M receptor
      in endothelium was pharmacologically identified on the basis of selective
      affinity of antagonists; ie, pirenzepine for M1, gallamine for M2, and 4
      diphenylacetoxy-N-methylpiperidine methiodide for M3. Our results showed that in
      the thoracic aorta of Wistar rats, 1) ACh-induced vasorelaxation was mediated by
      M3 receptor; 2) chronic exercise enhanced ACh-evoked vasodilating responses.
      However, this alteration was not caused by receptor upregulation, as maximal
      binding sites and affinity of M3 receptor were not changed by chronic exercise.
      Other possible mechanisms need to be further studied.

PMID- 9915127
TI  - Low susceptibility of stress ulcer in diabetic rats: role of cholinergic gastric
      motility.
AB  - The induction of gastric hemorrhage ulcer by cold restraint stress (CRS) and the
      changes of cholinergic gastric motilities were studied in streptozotocin (STZ)
      induced diabetic (DM) rats to compare with the age-matched normoglycemic rats.
      After receiving cold restraint stress for 4 h, a lower of both gastric motility
      and hemorrhagic ulcer was found in the STZ-induced diabetic rats in a time
      dependent way from 0-16 week (s) parallel with the induction of diabetes. The
      mucosal ulceration induced by CRS was correlated with the amplitude (r=0.8928,
      p<0.001) and frequency (r=0.8674, p<0.001) of gastric motility in diabetic rats.
      A significant (p<0.01) lowering of mucosal glutathione levels and mucus
      production also was observed in stressed diabetic rats. Under stress condition,
      the cholinergic gastric motility and mucosal lesion were markedly reduced by an
      intraperitoneal injection (i.p.) of atropine (1.0 mg/kg, i.p.) or bilateral
      vagotomy in 8-week STZ-DM rats. Otherwise, bethanechol (2.0 mg/kg, i.p.), 2-deoxy
      D-glucose (135 mg/kg, i.p.) and metoclopramide (20 mg/kg, i.p.) stimulated
      gastric motility and aggravated mucosal lesions significantly (p<0.05). It is
      indicated that cholinergic gastric motility was lowered in DM rats in a manner
      can decrease mucosal lesion induced by CRS.

PMID- 9915130
TI  - The involvement of nitric oxide in synergistic neuronal damage induced by beta
      amyloid peptide and glutamate in primary rat cortical neurons.
AB  - Abnormal extracellular accumulation of beta-amyloid (Abeta), the major component
      of senile plaques in the Alzheimer's brain and the excitatory amino acid
      glutamate are both considered to be associated with neurodegeneration. We studied
      whether nitric oxide (NO) was involved in neuronal damage induced by Abeta and
      glutamate in primary rat cortical neurons. Our results demonstrated that (1) Both
      neuronal damage and NO production were synergistically induced by Abeta-(25-35)
      and glutamate; (2) This synergistic neuronal damage induced by Abeta-(25-35) and
      glutamate was attenuated by selective inhibitors of NO synthase. We propose that
      cytotoxic characteristics of NO, at least in part, are involved in the
      synergistic neuronal damage induced by Abeta and glutamate, presumably seen in
      Alzheimer's brains.

PMID- 9915132
TI  - Implementation of new technologies in cytotechnology education.

PMID- 9915131
TI  - Fine-needle aspiration of the breast: cell counts as an illusion of adequacy. A
      clinical cytopathologist's point of view.

PMID- 9915133
TI  - Cytologic changes in cervical smears associated with prolonged use of depot
      medroxyprogesterone acetate.
AB  - BACKGROUND: Hormonal effects have always played a significant role in gynecologic
      cytology. In atrophic and postpartum smears, interpretation may be complicated by
      large numbers of parabasal cells with high nuclear cytoplasmic ratios and
      hyperchromatic nuclei that mimic precancerous lesions (squamous intraepithelial
      lesions, SILs). The authors have observed atrophic and postpartumlike changes in
      patients receiving depot-medroxyprogesterone acetate for prolonged periods. These
      alterations may lead to diagnostic uncertainty or falsely suggest the presence of
      SIL. METHODS: To evaluate the effect of chronic hormone use, smears from 29 depot
      medroxyprogesterone acetate users (average age, 35.9 years) who had been
      amenorrheic for 5-72 months (average, 22.6 months) were identified. This group
      was matched with 25 nonusers (average age, 31.9 years). Maturation values (MVs)
      were calculated for both groups and cellular findings were evaluated. RESULTS:
      The user group had a significantly lower MV (38.45 vs. 64.60, P < 0.001). Among
      users, 6 of 29 smears (21%) were abnormal. One low grade SIL was biopsy
      confirmed, but two high grade SILs and three smears of ASCUS had a negative
      Papanicolaou (Pap) smear and/or biopsy follow-up. Among nonusers, 4 of 25 smears
      (16%) were abnormal. Two patients with high grade SIL smears had positive biopsy
      or Pap smear follow-up, one with an ASCUS smear had a negative Pap smear follow
      up, and one with a low grade SIL was lost to follow-up. CONCLUSIONS: The immature
      cellular pattern seen in smears from long term depot-medroxyprogesterone acetate
      users led to difficulty in determining the diagnosis in some cases. ASCUS cases
      among users were associated with high nuclear cytoplasmic ratios and
      hyperchromasia in parabasal metaplasialike cells. Biopsies in these cases showed
      epithelial atrophy, which was often associated with acute inflammation. In view
      of the fact that long term depot-medroxyprogesterone acetate administration may
      induce changes that mimic high grade SIL in a population already at high risk for
      SIL, there may be problematic cases in which diagnostic uncertainty is
      inevitable.

PMID- 9915134
TI  - Urine cytology of primary and secondary urinary bladder adenocarcinoma.
AB  - BACKGROUND: Primary and secondary adenocarcinomas of the urinary bladder are
      uncommon, and the urine cytology of these tumors has rarely been described.
      Familiarity with the cytomorphology of these neoplasms may facilitate their
      detection in urine cytology specimens. METHODS: The authors reviewed 46 urine
      samples (19 voided, 19 instrumented, and 8 bladder washings) from 41 patients
      with biopsy-proven primary urinary bladder adenocarcinoma (n = 11) or metastatic
      adenocarcinoma (n = 35) from the prostate (n = 17), colon (n = 10), breast (n =
      3), kidney (n = 3), or uterus (n = 1), or from unknown origin (n = 1).
      Cytomorphology, the role of cytology, and causes for negative diagnoses were
      evaluated. RESULTS: Cytologic diagnoses of malignancy, adenocarcinoma not
      otherwise specified, and adenocarcinoma of a specific type were given in 87%,
      28%, and 39% of cases, respectively. Columnar cells, coarse chromatin, and
      necrosis were found in adenocarcinoma of the colon. Syncytial and acinar
      arrangements, round or oval nuclei, vesicular chromatin, and prominent nucleoli
      were commonly found in adenocarcinoma of the prostate. These features permitted
      us to make a specific diagnosis in 90% of cases of adenocarcinoma of the colon
      and 41% of cases of adenocarcinoma of the prostate. Cytologic examination failed
      to lead to a diagnosis of malignancy in 18% of primary adenocarcinoma cases.
      CONCLUSIONS: A large number of adenocarcinomas of the colon and prostate have
      sufficient cytologic features to suggest the correct diagnosis in urine samples.
      The cytomorphology of primary bladder adenocarcinoma is not as easily
      characterized. The submucosal nature of some metastatic deposits and tumor
      differentiation influence the diagnostic accuracy.

PMID- 9915135
TI  - Specimen adequacy and false-negative diagnosis rate in fine-needle aspirates of
      palpable breast masses.
AB  - BACKGROUND: As fine-needle aspiration (FNA) has become a critical component of
      the investigation of palpable breast masses, false-negative diagnoses have become
      a major concern, prompting reevaluation of the definition of specimen adequacy.
      Although cytopathologists agree that a number of parameters relate to the
      adequacy of an FNA specimen, there is no unanimity on the role of epithelial cell
      quantitation in the determination of an adequate FNA. To better understand the
      significance of epithelial cellularity, false-negative FNA samples from palpable
      breast lesions were reviewed. METHODS: False-negative FNA smears of palpable
      breast masses that had been performed and assessed immediately by
      cytopathologists were retrieved from the files of The University of Texas M. D.
      Anderson Cancer Center, and the number of epithelial cell clusters (ECCs) was
      determined. Aspirates were classified as adequate if a total of six or more ECCs
      (each comprised of at least five to ten well preserved cells) were present on all
      slides, or as inadequate if fewer than six ECCs were present. RESULTS: From 4455
      aspirates of palpable breast masses, 51 false-negative aspirates were identified,
      41 of which were available for review. No interpretative errors were identified.
      Twenty-one FNAs (51.2%) were classified as adequate and 20 FNAs (48.8%) as
      inadequate. The adequate false-negative aspirates contained between 8 to 100
      ECCs. A comparison of adequate and inadequate false-negative specimens showed no
      significant differences in the mean age of patients (56.4 years vs. 57.8 years),
      the mean number of FNA passes (3.7 passes vs. 3.0 passes), the mean palpation
      size of the lesions (2.8 cm vs. 2.9 cm), or the mean pathologic size of the
      lesions (2.1 cm vs. 2.2 cm). Cases of invasive lobular carcinoma were more common
      in the false-negative smears with fewer than six ECCs. CONCLUSIONS: Including the
      number of ECCs as a parameter of adequacy could reduce the rate of false-negative
      FNA diagnoses of palpable breast masses by approximately 50%. However, the
      presence or even abundance of ECCs does not eliminate the potential for a false
      negative cytologic diagnosis. Cytologic diagnoses must be correlated with
      clinical and imaging findings (the triple test) to reduce the rate of false
      negative cases, but benign triple test results do not entirely exclude the
      possibility of carcinoma, and such cases require periodic follow-up.

PMID- 9915136
TI  - Fine-needle aspiration diagnosis of the follicular variant of papillary
      carcinoma.
AB  - BACKGROUND: The follicular variant of papillary carcinoma (FVPC) presents
      significant diagnostic difficulty using fine-needle aspiration (FNA). Diagnoses
      by FNA vary considerably and usually are categorized as follicular
      proliferations. METHODS: Conventional Papanicolaou, Diff-Quik, and hematoxylin
      and eosin stained FNAs from 16 cases of histologically confirmed FVPC were
      examined retrospectively. Each case was evaluated with respect to easily
      recognizable architectural and cytologic features. These were defined, ranked,
      and recorded for side-by-side comparison and identification of statistical
      significance. Similar features in six follicular carcinomas, seven follicular
      adenomas, and six adenomatous multinodular goiters were evaluated and compared as
      well. RESULTS: Eight of 16 FVPC cases (including 5 macrofollicular variants)
      previously were diagnosed on FNA as a follicular neoplasm or follicular lesion, 6
      were diagnosed as a papillary carcinoma or FVPC, and the remaining 2 were
      diagnosed as atypical. The cellularity and amount of colloid varied considerably
      between cases. Monolayered, twisted epithelial sheets and microfollicles or
      macrofollicles were the predominant microarchitecture. Powdery chromatin and
      easily identifiable nuclear grooves were present in 15 cases (94%), and
      intranuclear cytoplasmic (INC) inclusions were present in 11 cases (69%). These
      three features proved to be statistically significant in distinguishing FVPC from
      the other follicular lesions. No case exhibited true papillary clusters or
      psammoma bodies. Cases of follicular adenoma, follicular carcinoma, and
      adenomatous goiter shared many of these features, but notably lacked INC
      inclusions and abundant nuclear grooves. CONCLUSIONS: Nuclear features such as
      abundant grooves, powdery chromatin, and INC inclusions were statistically
      significant and present in combination in the majority of cases of FVPC compared
      with the other follicular proliferations examined.

PMID- 9915137
TI  - The stability of estrogen and progesterone receptor expression on breast
      carcinoma cells stored as PreservCyt suspensions and as ThinPrep slides.
AB  - BACKGROUND: Analysis of estrogen receptor (ER) and progesterone receptor (PR)
      status is an important ancillary test in the evaluation of positive breast fine
      needle aspirates. This study compares the detection of ER and PR in breast
      carcinoma cells suspended in PreservCyt with that achieved with stored ThinPrep
      slides (TP). METHODS: ER and PR positive mammary tumor cells (cell line ZR-75-1
      spiked in PreservCyt by the American Type Culture Collection) were used to
      evaluate the stability of immunodetection of ER and PR under two conditions: 1)
      TP slides prepared immediately from PreservCyt and stored air-dried (stored TP)
      for up to 56 days, and 2) TP prepared from cells suspended in PreservCyt (newly
      prepared TP) on Days 1, 2, 5, 14, 21, 42, and 56. At each of the time periods,
      stored TP and newly prepared TP were analyzed for ER and PR using the same
      immunocytochemical staining protocol. The percentage of positive cells was
      calculated by counting 1000 cells/TP. RESULTS: Positivity for ER and PR was
      demonstrated in both stored TP and newly prepared TP on Days 1, 2, 5, 14, 21, 42,
      and 56. Over the 56-day period, the number of ER positive cells ranged from 41%
      to 57% in stored TP and from 38% to 58% in newly prepared TP. The number of PR
      positive cells ranged from 31% to 41% in stored TP and from 26% to 37% in newly
      prepared TP. Mild, nonspecific cytoplasmic and nuclear staining occurred in all
      newly prepared TP (PR > ER). CONCLUSIONS: ER and PR antigenicity was preserved in
      both stored TP and newly prepared TP of mammary tumor cells over a 56-day storage
      period. This demonstrates that ER and PR status can be evaluated in cytologic
      material from breast carcinoma using the ThinPrep technique.

PMID- 9915138
TI  - Rescreening of atypical cervicovaginal smears using PAPNET.
AB  - BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is a
      cytopathologic term used to describe cases without specific pathologic
      substratum. Between 10-60% of ASCUS cases correspond to squamous intraepithelial
      lesions (SIL). METHODS: The objectives of this study were: 1) to detect the
      pathologic significance of ASCUS in study patients, 2) to determine whether
      PAPNET identifies these cases, and 3) to compare the results of PAPNET with those
      of a second conventional screening. One hundred and sixty-three consecutive
      patients with the cytologic diagnosis of ASCUS and adequate follow-up were
      selected. Of these, 111 patients had colposcopic lesions and biopsies were
      performed; in the remaining 52 cases colposcopy was negative, as were 3
      consecutive annual Papanicolaou smears. In a blind review, all 163 cases were
      rescreened using PAPNET. A second manual screening was performed for comparison.
      RESULTS: One hundred and twenty-six of the 163 cases (77.3%) showed no SIL on
      biopsy or follow-up. Of the 37 pathologic cases, the diagnosis was koilocytosis
      (flat condyloma) in 13 cases (8%), cervical intraepithelial neoplasia (CIN) type
      I in 11 cases (6.8%) low grade SIL [LSIL] in a total of 24 cases [14.8%]), and
      CIN II-III or high grade SIL (HSIL) in 11 cases (6.8%). In the review using
      PAPNET, 57 previous ASCUS cases were classified correctly as negative, and 7 of
      13 koilocytosis cases (54%), 9 of 11 CIN I cases (82%), and 7 of 11 CIN II-III
      cases (64%) were diagnosed correctly. In the second conventional screening, 74
      cases were negative and 77 cases were ASCUS; only 3 of 13 koilocytosis cases
      (23%), 4 of 11 CIN I cases (36.4%) and 5 of 11 CIN II-III cases (45.5%) were
      reclassified correctly. CONCLUSIONS: Among 163 patients with ASCUS, 77.3% had no
      precancerous squamous lesions. Concordance with definitive diagnosis was more
      accurate in our study using PAPNET analysis (Kappa index [K] = 0.7158) than by
      second conventional screening (K = 0.4537). Furthermore, we reclassified 35% of
      smears as negative and 15% as SIL.

PMID- 9915139
TI  - Evidence of intrinsic differences in the light scattering properties of
      tumorigenic and nontumorigenic cells.
AB  - BACKGROUND: The objective of this study was to determine whether there are
      intrinsic differences in the light scattering properties of tumorigenic and
      nontumorigenic cells from a multistep carcinogenesis model. METHODS: Wavelength
      dependent and polarization-dependent light scattering properties of cell
      suspensions were measured. RESULTS: Statistically significant differences were
      found between the tumorigenic and nontumorigenic cells. CONCLUSIONS. Differences
      in the light scattering properties of tumorigenic and nontumorigenic cells are
      attributed to a change in the average size of the scattering centers on the order
      of a few ten of nanometers. This work is relevant to the development of
      noninvasive optical methods for cancer diagnosis.

PMID- 9915140
TI  - Distinct cytogenetic alterations in squamous intraepithelial lesions of the
      cervix revealed by laser-assisted microdissection and comparative genomic
      hybridization.
AB  - BACKGROUND: It has been established that comparative genomic hybridization (CGH)
      on Papanicolaou-stained cervical smears can be used to identify chromosomal
      imbalances. METHODS: In this study, the authors identified normal and dysplastic
      squamous epithelial cells cytologically, eliminated surrounding bacteria or
      leukocytes by a ultraviolet laser microbeam under microscopic control, and
      scraped out the cell groups of interest by a microdissection system. In 3 cases
      of squamous intraepithelial lesions (SIL), a total of 9 samples of dysplastic (n
      = 6) and nontumorous cells (n = 3) were investigated, each of them consisting of
      3-40 cells. The DNA was amplified by degenerate oligonucleotide primed PCR (DOP
      PCR) and used for CGH. RESULTS: Analyses of all nontumorous cell groups resulted
      in fluorescence ratio profiles that showed no deviation from the normal range,
      confirming that no methodologic artefacts have been produced. The CGH profiles
      from dysplastic cells, however, showed various chromosomal imbalances affecting
      six to nine different chromosomes. The most frequent gains in DNA were observed
      on chromosomes 1p, 2q, 4, and 5, whereas losses were found on chromosomes 6q and
      13q. CONCLUSIONS: The results of this study demonstrate the feasibility and
      reliability of CGH on microdissected cell samples of routinely processed cervical
      smears. To the authors' knowledge, this is the first study reporting the use of
      CGH on cervical routine smears. This approach offers the opportunity to
      investigate sequence copy number changes in small, morphologically well-defined
      groups of dysplastic cells. It may, therefore, serve as a cytogenetic screening
      test for identifying chromosomal aberrations in precancerous lesions that are
      associated with a high risk for progression to invasive cancer.

PMID- 9915141
TI  - Recent advances in the diagnosis in livestock of Cryptosporidium, Toxoplasma,
      Giardia and other protozoa of veterinary importance.

PMID- 9915142
TI  - Effect of stage of gestation and foetal number on plasma concentrations of a
      pregnancy serum protein (PSP-60) in cattle.
AB  - This study characterised the peripheral plasma concentration of PSP-60 throughout
      gestation, and examined the effect of stage of gestation and foetal number on
      this protein in Holstein cows after non-surgical embryo transfer. Cows (n=12)
      were divided into two groups; Group 1 contained single embryo recipient cows
      (n=5), Group 2 contained twin-embryo recipient cows (n=7). Blood was collected
      approximately every third day from day 0 (first day of standing oestrus), then
      daily for the last 10 days of gestation and until one day post-partum. Two of the
      twin-embryo recipient cows had abnormal pregnancies, consequently data from them
      was considered separately. In both groups PSP-60 increased progressively from
      about day 20 post-oestrus to 20 days pre-partum (from 0.9 +/- 0.2 to 49.7 +/- 8.7
      ng ml(-1), and from 1.3 +/- 0.6 to 115 +/- 34.9 ng ml(-1) (mean +/- SEM), in
      singleton and twin-bearing groups, respectively). The mean concentrations between
      20 and 10 days pre-partum increased dramatically by about six-fold (P<0.001) in
      singleton-bearing cows (from 49.7 +/- 8.7 ng ml(-1) to 283.8 +/- 73.7 ng ml(-1))
      to over two-fold in twin-bearing cows (from 115 +/- 34.9 ng ml(-1) to 284 +/-
      98.2 ng ml(-1)). The mean concentrations of the two groups were indistinguishable
      between 10 days pre-partum and parturition. Cows giving birth prematurely to
      stillborn calves or to a schistosomus reflexus calf exhibited abnormal PSP-60
      profiles. Our findings indicate that peripheral plasma PSP-60 concentrations are
      correlated to the stage of gestation and foetal number, and assist in predicting
      foeto-placental viability.

PMID- 9915143
TI  - Efficacy of phosphomycin in the control of Escherichia coli infection of broiler
      chickens.
AB  - Seventy-five 25-day-old broilers were divided into three groups: group I
      unmedicated and challenged with E. coli O78:K80; group F infected and treated
      with 150 ppm of phosphomycin in their drinking water, and group C acted as a
      control. Their weights, feed intake, clinical signs, macroscopic lesions, E. coli
      reisolation, and serum biochemistry were compared. Group F showed fewer symptoms
      and gross lesions than those from group I while the average daily gain,
      bodyweight, and feed intake were similar to the control group. E. coli was
      reisolated in 32 per cent of the livers and spleens from group I, compared with 4
      per cent of liver and 8 per cent of spleens from group F. There was an increase
      in the levels of total protein and globulins in group I but not in group F. These
      results provide evidence of the therapeutic efficacy of phosphomycin in the
      control of an experimental E. coli infection in broiler chickens.

PMID- 9915144
TI  - Immunoglobulin isotype distribution of antinuclear antibodies in dogs with
      leishmaniasis.
AB  - A modified indirect immunofluorescence method, using rat liver as substrate, was
      developed to determine the immunoglobulin isotypes forming antinuclear antibodies
      in sera from 12 antinuclear antibody-positive dogs out of 121 dogs with natural
      Leishmania infection. Immunoglobulin M was found to be the most frequent
      component of antinuclear antibodies (91.7 per cent), followed by IgG (41.7 per
      cent) and IgA (33.2 per cent). When these immunoglobulin isotypes were titrated,
      IgG antinuclear antibodies showed higher titres (1:200) than IgM and IgA
      antinuclear antibodies (1:50 and 1:20 respectively). Most of the antinuclear
      antibody-positive dogs simultaneously had two immunoglobulin isotypes, whereas
      none had all three immunoglobulin isotypes at the same time. Spearman rank
      correlation analysis showed no significant correlation between antinuclear
      antibody titres and circulating immune complexes or immunoglobulin levels. The
      low incidence of antinuclear antibodies and the absence of a clear relationship
      between isotype titres and clinical signs suggest a minor pathogenic role of
      antinuclear antibodies in canine leishmaniasis.

PMID- 9915145
TI  - Pharmacokinetics of oxytetracycline after intramuscular administration with
      lidocaine in sheep, comparison with a conventional formulation.
AB  - The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep
      after intravenous and intramuscular administration at a single dosage of 20 mg
      kg(-1) bodyweight. A conventional formulation was injected by the intravenous
      route and two different preparations were administered by the intramuscular
      route: a conventional formulation (T-100) and an aqueous solution of OTC with
      lidocaine (1 per cent) (OTC-L). The objective was to determine whether there are
      differences between both formulations in the disposition kinetics of OTC after
      intramuscular administration to sheep. After intravenous administration of the
      conventional formulation, plasma oxytetracycline concentrations were best fitted
      to an open two-compartment model. Mean apparent volume of distribution was 0.77+/
      0.02 litre kg(-1) and the harmonic mean half-life was three hours. The OTC
      transfer process between central and peripheral compartments was fast and that
      did not influence the elimination process. After intramuscular administrations of
      both formulations, half-lives were longer than after intravenous administration
      (mean values of 14.1 and 58.2 hours for T-100 and OTC-L respectively). In both
      cases, a biphasic absorption, a 'flip-flop' model and a complete bioavailability
      were found. OTC-L provided therapeutic plasma concentrations over 0.5 microg ml(
      1) (the minimum inhibitory concentration for most susceptible pathogens) for a
      longer period of time than T-100 (72 hours compared with 36 or 48 hours).

PMID- 9915146
TI  - Improved hepatic and pancreatic localisation of the equine alpha-1-proteinase
      inhibitor family of serpins using an antigen enhancement technique and a
      monoclonal antibody.
AB  - Equine alpha-1-proteinase inhibitor (API) consists of three, occasionally four,
      serum glycoproteins. This study investigated the immunohistochemical localisation
      of equine API in paraformaldehyde fixed, paraffin embedded equine tissue samples
      of liver, lung, stomach, pancreas, jejunum and colon in five horses using
      affinity purified sheep polyclonal and protein A purified mouse monoclonal
      antibodies, whose specificities were verified by Western blotting. Exposing
      tissue sections to boiling citrate buffer greatly enhanced antigen recovery and
      improved immunostaining with both antibodies, resulting in discovery of novel
      tissue distribution patterns for the horse. In the horses studied, all
      hepatocytes showed some degree of cytoplasmic staining, many having perinuclear
      intense granular inclusions. This finding is contrary to findings in human
      studies where hepatocytes of Pi MM phenotype have proven difficult to stain for
      human API, despite evidence at the molecular level suggesting hepatocytes as the
      major source of serum API. This discrepancy may be due to the use of different
      tissue fixation and antigen recovery techniques. In all other tissues examined,
      the distribution of equine API was similar to human studies.

PMID- 9915147
TI  - Ki-67 index as indicator of the post-surgical prognosis in feline mammary
      carcinomas.
AB  - Forty-eight feline mammary carcinomas (FMC) were resected surgically from 48 cats
      to determine whether the Ki-67 index (Ki-67I) would provide an indication of the
      post-surgical survival time (PST). Twenty-four cats (50 per cent) were still
      alive (group A) one year after surgery, whilst 24 (50 per cent) (group B) had
      died. Formalin-fixed, paraffin wax-embedded histological sections were
      immunostained with a monoclonal antibody to Ki-67 (MIB-1) and at least 1000
      nuclei in eight to 10 representative fields were counted. The Ki-67I was
      expressed as the percentage of positive nuclei. In FMC, the Ki-67I ranged from
      7.5 to 49.7 (24.8+/-9.5). A statistically significant difference (P = 0.000006)
      in the Ki-67I was found between group A and group B cats. No other statistically
      significant differences were found between these groups. The Ki-67I did not
      correlate with age or different histological type, according to the WHO
      classification. A Ki-67I cut-off of 25.2 represents a useful tool for identifying
      FMC with a more aggressive course.

PMID- 9915148
TI  - The cardiopulmonary effects of clenbuterol when administered to dorsally
      recumbent halothane-anaesthetised ponies--failure to increase arterial
      oxygenation.
AB  - Clenbuterol (0.8 microg kg(-1) intravenously) was investigated in ponies (small
      horses) anaesthetised with acepromazine, detomidine and thiopentone, then
      halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic
      group). Following instrumentation, ponies were placed in dorsal recumbency for 60
      minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given,
      and cardiopulmonary parameters monitored for a further 60 minutes. In the
      hyperoxic group, clenbuterol administration resulted in a transitory (<five
      minutes) 15 per cent fall in arterial blood pressure and 78 per cent rise in
      intramuscular blood flow. Heart rate increased from a mean of 42 (SD 4) to 54
      (12) beats per minute, the rise being significant for 15 minutes. Cardiac index
      increased from 2.1 (0.7) to 3.9 (0.7) litres m(-2) and remained significantly
      elevated for the remainder of the measurement period. Cardiovascular changes in
      the hypoxic group were similar. 30 minutes after clenbuterol administration, PaO2
      had changed nonsignificantly from 32.3 (19.2) to 33.4 (17) kPa in the hyperoxic
      group and from 7.9 (1.8) to 8.6 (1.3) kPa in the hypoxic group. The study
      concludes that under these experimental conditions, clenbuterol does not cause
      significant improvement in arterial oxygenation, but its cardiovascular effects
      are minimal or advantageous.

PMID- 9915149
TI  - Gait analysis of poultry.
AB  - Lameness is a major problem in the UK poultry industry, however, relatively few
      objective studies have been undertaken into the biomechanics of normal walking in
      these birds. In this study, the use of a pedobarograph as a novel method of gait
      analysis in poultry was investigated. Unlike most systems, the pedobarograph has
      a recording surface with a high degree of spatial resolution, allowing pressure
      patterns to be established for various regions of the foot. The highest pressures
      were found to act on the medial toe (149.4-218 kN m(-2)) and back toe (146.1
      195.5 kN m(-2)). The metatarsal pad, a region often associated with lesions, was
      subject to lower pressures (16.3-131.2 kN m(-2)). Maximum net forces of 116-145
      per cent of bodyweight were found during normal walking, an order of the same
      magnitude as human bipeds. Routine spatial parameters were also measured,
      allowing further characterisation of the gait patterns.

PMID- 9915150
TI  - Continuous and non-invasive study of brain oxygenation in the calf by near
      infrared spectroscopy.
AB  - Near infrared spectroscopy (NIRS) was used to detect changes in brain oxygenation
      in five tranquilised calves that were placed on a hypoxic gas mixture (10 per
      cent O2/90 per cent N2) and hyperoxic gas mixture (30 per cent O2/70 per cent N2)
      for five minutes at each concentration. A NIRO 500 (Hamamatsu, Japan) was used
      for the NIRS, with the incident light source and separate detector (optodes)
      placed on shaved skin on the most dorsal surface of the frontal bone. Sequential
      arterial blood gas sample analyses provided confirmation of the appropriate
      change in systemic oxygenation status. By the end of the five-minute-period of
      breathing 10 per cent oxygen, NIRS of the calf head detected highly significant
      changes in haemoglobin oxygenation reflective of hypoxaemia, with oxyhaemoglobin
      decreasing by 23.5 units (P<0.01) and deoxyhaemoglobin increasing by 45.6 units,
      (P<0.01) from the baseline of breathing room air. Total haemoglobin
      (oxyhaemoglobin + deoxyhaemoglobin) showed a significant increase of 22.1 units
      (P<0.05) but there was no significant change in NIRS determined cytochrome aa3
      oxygenation. Concomitant blood gas alterations included significant decreases in
      PaO2 (-27.8 mmHg, P<0.01), haemoglobin saturation (-29.0 per cent, P<0.05), and
      PaCO2 (-7.8 mmHg, P<0.05) and significantly increased blood pH (0.059, P<0.05).
      At the end of the five minutes of breathing 30 per cent oxygen NIRS of the calf
      head detected significantly increased oxyhaemoglobin (13.1 units, P<0.01) and
      decreased deoxyhaemoglobin (-13.7 units, P<0.05) when compared with baseline
      breathing of room aim. Total haemoglobin and cytochrome aa3 were unchanged from
      baseline. The accompanying arterial blood gas changes included significant
      increases in PaO2 (30.9 mmHg, P<0.05), arterial O2 saturation (11.7 per cent,
      P<0.05), and significantly decreased pH (-0.026, P<0.05). This study showed that
      NIRS can be used to continuously and non-invasively detect cerebral oxygenation
      changes in the live calf in response to both increased and decreased systemic
      arterial oxygen. Additionally, despite induction of profound hypoxaemia,
      cytochrome aa3 in the brain did not appear to become reduced.

PMID- 9915151
TI  - Comparison of transdermal fentanyl and intramuscular oxymorphone on post
      operative behaviour after ovariohysterectomy in dogs.
AB  - The effects of transdermal fentanyl and i.m. oxymorphone on behavioural and
      physiological responses, after ovariohysterectomy in dogs, were investigated. The
      study involved three groups of 10 dogs: fentanyl/surgery (FS),
      oxymorphone/surgery (OS), fentanyl/control (FC). A transdermal fentanyl delivery
      system (50 microg hour(-1)) (FS and FC) was applied 20 hours before surgery, or
      i.m. oxymorphone (OS) was administered. After ovariohysterectomy (FS and OS) or
      anaesthesia alone (FC), dogs were continuously videotaped for 24 hours and a
      standardised hourly interaction with a handler performed. The videotapes were
      analysed, and interactive and non-interactive behaviours evaluated. In addition,
      pain and sedation scores, pulse and respiratory rates, rectal temperature,
      arterial blood pressure, plasma cortisol and plasma fentanyl concentrations were
      measured. This study showed that transdermal fentanyl and i.m. oxymorphone (0.05
      mg kg(-1)) produced comparable analgesic effects over a 24 hour recording period.
      I.m. oxymorphone produced significantly more sedation and lower rectal
      temperatures than transdermal fentanyl. There were no significant differences
      between groups in respiratory and heart rates, and arterial blood pressures.

PMID- 9915152
TI  - Enteroplication in cats, using suture of N-butyl cyanoacrylate adhesive.
AB  - Enteroplication has been recommended to prevent recurrence of intussusception in
      dogs and cats. This study investigated the impact of enteroplication on
      subsequent function of the plicated small intestine as measured by transit time
      of barium impregnated polyethylene spheres (BIPS) and compared two methods of
      achieving enteroplication--sutures using polydioxanone and cyanoacrylate tissue
      adhesive. Twenty-two healthy young cats were used--four controls, nine sutured
      and nine glued. The mean +/-SD transit times before, one week after and four
      weeks after enteroplication were respectively 2.0+/-0.80 hours, 1.6+/-0.80 hours,
      2.2+/-1.18 hours. There was no significant difference in transit time or in the
      time to create enteroplication in the two plicated groups. Maintenance of
      intestinal adhesion was greater for the sutured plications. There was no
      significant change in internal diameter with either technique. Adverse clinical
      signs after enteroplication were not severe, however, they were more prevalent in
      cats which had glued plication. The inflammation associated with the suture was
      of a greater depth initially but that associated with the adhesive was more
      widespread and persisted for the four weeks of the experiments. Enteroplication
      in cats was a relatively benign procedure which did not cause significant
      alterations in small intestinal function. However, cyanoacrylate tissue adhesive
      cannot be recommended for this clinical procedure.

PMID- 9915153
TI  - Evaluation of a micro method for the routine determination of serum pepsinogen in
      cattle.
AB  - Estimation of serum pepsinogen concentration in cattle is used to aid the
      detection of clinical or subclinical infections with the abomasal nematode
      Ostertagia ostertagi. An inexpensive, simple micro method for the routine
      determination of pepsinogen concentration in bovine serum samples is described
      which is based on the hydrolysing effect of serum on buffered bovine albumin
      substrate. Comparison of this assay with a macro method, based on the same
      principle, gave almost identical results in the range of 0 to 10 Units tyrosine.
      The reproducibility of the assay was shown to be very satisfactory, intra-assay
      and day-to-day coefficients of variations were less than 4.7 and 8 per cent,
      respectively.

PMID- 9915154
TI  - Concentrations of energy substrates in oviduct fluid in unilaterally
      ovariectomised pigs.
AB  - Nichol et al (1992, Journal of Reproduction and Fertility, 96, 699-707)
      identified a pre- to post-ovulatory decrease (approx 1 mM) in the amount of
      glucose in pig oviduct fluid. The present studies investigated whether the
      decrease was due to metabolism by embryos and/or oviduct tissues, and also
      whether there was a local influence of the ovary on the oviduct fluid content of
      energy substrates. Unilaterally ovariectomised pigs were used, in which, through
      compensation, oviducts that contained twice the normal number of embryos could be
      compared with oviducts which contained no embryos. Following unilateral
      ovariectomy and after two oestrous cycles of normal duration, surgery was
      performed 88 hours after the beginning of standing heat to obtain oviduct fluid
      samples, just before embryonic entry into the uterus. Luminal fluid samples from
      the ampulla and ampullary-isthmic junction from oviducts with and without an
      adjacent ovary were assayed for glucose, pyruvate and lactate concentrations. No
      significant differences were found between the glucose, pyruvate and lactate
      concentrations in fluids from the ampulla or ampullary-isthmic junction from
      oviducts containing embryos compared with absence of embryos (P > 0.05).
      Therefore, the post-ovulatory decrease was not due to the presence of embryos or
      to a local effect of the ipsilateral ovary. Consequently, pig oviduct fluid
      concentrations of glucose, lactate and pyruvate are seemingly regulated by
      systemic mechanisms.

PMID- 9915155
TI  - Haemangiopericytoma in a calf.
AB  - After castration, a Japanese Black male calf developed subcutaneous tumours near
      the scrotum. They were surgically excised, and no recurrence was detected two
      years after surgery. The tumours were characterised by neoplastic cells
      concentrically arranged around blood vessels of various sizes. The neoplastic
      cells contained many cytofilaments, and the majority of the cells expressed
      smooth muscle actin, but focal densities were not found. On the basis of the
      immunohistochemical and ultrastructural features, the tumours were considered to
      be of pericyte origin.

PMID- 9915156
TI  - The effect of dietary protein levels before turnout on subsequent faecal nematode
      egg output of grazing sheep in the Joannina region of Greece.
AB  - The effect of dietary protein levels before turnout on the subsequent faecal egg
      output of gastrointestinal nematodes was examined in two genotypes of grazing
      sheep, with or without anthelmintic treatment. Lambs were given a low protein
      (LP) or a high protein (HP) diet for three months (December to March) until
      grazing started. Half of the animals in each diet group were given anthelmintic
      treatment (AT) in March and June. The four groups (LP-AT, LP-NT, HP-AT and HP-NT)
      each consisted of pure-bred Butsiko and cross-bred Butsiko/Karamaniko lambs and
      grazed separate plots that were initially parasitologically and nutritionally
      similar. Faecal egg counts were recorded monthly until the experiment ended in
      July. Mean faecal counts for strongyle-type eggs were higher in the LP-NT group
      than all the other groups and higher in the LP than the HP groups indicating that
      faecal egg counts during grazing were influenced by levels of dietary protein
      before turnout. This effect was intensified in the absence of anthelmintic
      treatment. No genotype differences were detected.

PMID- 9915157
TI  - Proliferative hemangiomas: analysis of cytokine gene expression and angiogenesis.
AB  - Hemangiomas are benign vascular tumors of childhood that can lead to
      disfigurement and/or life-threatening consequences. The pathogenesis of
      hemangioma formation is likely to involve increased angiogenesis. Basic
      fibroblast growth factor and vascular endothelial growth factor are cytokines
      that stimulate angiogenesis in multiple in vivo and in vitro models.
      Proliferative hemangiomas have been found to have elevated levels of basic
      fibroblast growth factor and vascular endothelial growth factor protein, but the
      gene expression of these cytokines in human specimens has not been previously
      studied. We examined the gene expression and spatial distribution of basic
      fibroblast growth factor and vascular endothelial growth factor messenger RNA in
      proliferative versus involuted human hemangioma specimens using nonisotopic in
      situ hybridization techniques. Thirteen hemangioma specimens were harvested
      during initial surgical excision. In situ hybridization was performed on frozen
      sections of both proliferative and involuted hemangioma specimens using
      genetically engineered antisense probes specific for basic fibroblast growth
      factor and vascular endothelial growth factor messenger RNA. Controls were an
      interleukin-6 sense sequence and a transforming growth factor-beta 1 antisense
      sequence. A large number of cells within the specimens of proliferative
      hemangiomas revealed localized gene expression of basic fibroblast growth factor
      and vascular endothelial growth factor messenger RNA (626 +/- 129 and 1660 +/-
      371 cells/mm2, respectively). The majority of the cells were endothelial in
      origin. In contrast, involuted hemangioma specimens revealed significantly lower
      numbers of cells staining positive for basic fibroblast growth factor and
      vascular endothelial growth factor messenger RNA (44 +/- 11 and 431 +/- 76
      cells/mm2, respectively; p < 0.05). Transforming growth factor-beta 1 messenger
      RNA was slightly more expressed by involuted hemangiomas (117 +/- 30 cells/mm2).
      There were very low levels of transforming growth factor-beta 1 gene expression
      from proliferative hemangiomas (37 +/- 24 cells/mm2; p < 0.02). These data
      demonstrate that (1) in situ hybridization allows identification and relative
      quantitation of cells expressing messenger RNA for specific growth factors in
      human hemangioma specimens; (2) basic fibroblast growth factor and vascular
      endothelial growth factor messenger RNA are up-regulated in proliferative
      hemangiomas; and (3) transforming growth factor-beta 1 messenger RNA remains low
      in both proliferative and involuted hemangiomas. Because basic fibroblast growth
      factor and vascular endothelial growth factor messenger RNA have been implicated
      in the pathobiology of human hemangioma formation, biochemical modulation of
      these angiogenic cytokines may eventually help inhibit proliferation and promote
      regression of hemangiomas.

PMID- 9915158
TI  - Intralesional photocoagulation of periorbital hemangiomas.
AB  - The purpose of this study was to examine the effects of intralesional bare fiber
      photocoagulation with the KTP and Nd:YAG lasers on periorbital hemangiomas of
      infancy. Initial reports by Apfelberg and Gregory suggest that intralesional
      laser therapy may have a role in the treatment of hemangiomas. Intralesional
      photocoagulation may be preferred to superficial laser treatment for several
      reasons. It may decrease cutaneous skin damage and more effectively reduce bulky,
      deep lesions. Twenty-three patients with periorbital hemangiomas were treated
      (KTP, n = 7; Nd:YAG, n = 16). An 18-g Angiocath was placed into the lesion to
      pass the fiber through. Laser energy was delivered by means of a 0.6-mm bare
      fiber at 10 to 15 J (KTP) or 7 J (Nd:YAG). Treatments were done under general
      anesthesia. Patients were followed closely for 1 month and then monthly to assess
      results and complications. Results are as follows: 61 percent demonstrated 50
      percent or more reduction at 3 months; 22 percent demonstrated 50-percent or more
      reduction in 3 to 8 months, i.e., 83 percent of patients had 50-percent or more
      reduction within 8 months. To achieve these results, two patients required two
      treatments. The remaining 17 percent had 10- to 14-percent reduction at 1 to 3
      months. Two of these patients had two treatments. A subgroup of patients had a
      very dramatic response. Thirty-five percent (8 of 23) had 50- to 90-percent
      reduction in 1 month. It is unclear why these patients responded so dramatically.
      We expected some ulceration during the healing phase. Seventeen percent developed
      ulceration. Complications were limited (4 percent) to one wound infection.
      Intralesional photocoagulation treatment with the KTP and Nd:YAG lasers is
      effective and safe for the treatment of periorbital hemangiomas in the majority
      of patients with minimal complications. Further study is necessary to identify
      factors that result in dramatic or limited responses.

PMID- 9915159
TI  - Properties of coralline hydroxyapatite and expanded polytetrafluoroethylene
      membrane in the immature craniofacial skeleton.
AB  - Although extensive research regarding the treatment of calvarial defects has been
      done in adult models, little is known about the response in the maturing
      skeleton. The role of coralline hydroxyapatite and expanded
      polytetrafluoroethylene membrane in augmenting bone growth and repair of
      calvarial defects in a neonatal model is explored. Utilizing a 3-week-old
      neonatal swine model, bone growth into 28 calvarial defects was measured. After
      exposure of the calvaria in seven animals, four defects of 10 mm in diameter were
      created. In each animal, one defect was treated with a 10-mm disc of porous
      hydroxyapatite alone (Interpore 500, Interpore International), and a second
      defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV
      6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The
      third defect combined an implanted hydroxyapatite disc covered by an expanded
      polytetrafluoroethylene membrane, whereas the fourth defect served as an
      untreated control. Histology and histomorphometry were performed on undecalcified
      specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the
      bone growth into the inorganic matrix provided complete osseous union in all
      specimens, and the amount of fibrosis was significantly lower (p < 0.02) in
      comparison with the control. Unexpectedly, there was significant osteoclastic
      resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous
      bone deposition and remodeling. The addition of an expanded
      polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an
      insignificant advantage in bone growth (27.3 percent versus 28.3 percent,
      respectively). Finally, the expanded polytetrafluoroethylene membrane alone
      afforded no qualitative advantage secondary to intrusion of brain and dura into
      the defect as well as displacement of the membrane inward during appositional
      growth, leading to incomplete healing of the defect with thinning of the
      surrounding cranial bone. Unique in this maturing model was morphologic evidence
      of complete union at the calvaria-hydroxyapatite interface in all specimens as
      well as active remodeling of the hydroxyapatite matrix. The results of this study
      suggest that porous hydroxyapatite may be a suitable bone substitute in maturing
      calvarial bone defects, achieving superior osseous integration and volumetric
      bone gain while undergoing concurrent resorption and remodeling.

PMID- 9915160
TI  - Airway disorders in hemifacial microsomia.
AB  - The anatomic components of hemifacial microsomia have been classified previously,
      but their relevance to functional abnormalities has not been stressed. In a
      recent review of the literature, we found that the frequency and severity of
      airway disorders, especially those leading to upper airway obstruction and/or
      obstructive sleep apnea, had not been reported. Accordingly, a retrospective
      study of 38 patients (21 male, 17 female), aged 6 months to 22 years (mean, 8
      years 3 months) with hemifacial microsomia was undertaken to ascertain the
      frequency and severity of airway disorders in hemifacial microsomia. Upper airway
      disorders fell broadly within three categories: group I (n = 22, 58 percent) was
      asymptomatic for airway disturbances; group II (n = 7, 18 percent) had a medical
      history suspect for intermittent obstructive sleep apnea or had a perioperative
      apneic event; and group III (n = 9, 24 percent) had a definite history of
      obstructive sleep apnea or upper airway obstruction requiring tracheotomy or
      apnea surgery. Group III versus groups II and I had a higher incidence of
      bilateral involvement (33 percent versus 14 percent and none), a greater
      percentage of M2, M2a, M2b, and M3 mandibular deformities (88.9 percent versus
      28.6 percent and 18.2 percent), more severe orbital involvement (33 percent O2
      and O3 versus none in group II and 9 percent in group I), and more severe soft
      tissue involvement (89 percent S2 and S3 versus 29 percent and 23 percent).
      Patients with more severe mandibular and orbital deformities, but not ear or
      vertebral abnormalities, appear at a greater risk for obstructive sleep apnea.
      The relationship of OMENS-Plus (extracraniofacial anomalies) to apnea was
      variable but was found more commonly in group II (86 percent) and group III (56
      percent) than in group I (32 percent) patients. Group III patients had a higher
      frequency of cardiac anomalies (44 percent versus 29 percent in group II and 23
      percent in group I). The incidence of obstructive sleep apnea in our population
      of patients with hemifacial microsomia approaches 24 percent. Patients with
      hemifacial microsomia should undergo routine screening for obstructive sleep
      apnea: a positive history warrants polysomnographic and anatomic workup.

PMID- 9915161
TI  - Natural history of fetuses with cleft lip.
AB  - The prospect of fetal surgery for cleft lip is predicated on our ability to
      accurately identify fetuses with clefts and exclude those that have associated
      anomalies. Prenatal ultrasound is currently the most appropriate means with which
      to do this. We reviewed the ultrasonographic data from two large perinatal
      referral institutions to determine the natural history of fetuses with cleft lip
      who may be candidates for fetal surgery. Forty fetuses had a cleft lip diagnosed
      prenatally by ultrasound. In this group, severe associated anomalies were common
      (30 of the 40) and multiple (23 of the 40) in a majority of fetuses. Life
      threatening anomalies, such as central nervous system and cardiac anomalies, were
      the most common defects. As a result, many fetuses were aborted therapeutically
      or died in the perinatal period. Out of 12 surviving fetuses, only six had
      isolated clefts, and two surviving fetuses, diagnosed with isolated cleft lip,
      had no defect identified postnatally. This information has important implications
      for the perinatal management of fetuses with cleft lip and the potential role of
      fetal intervention.

PMID- 9915162
TI  - Double free flaps in reconstruction of extensive composite mandibular defects in
      head and neck cancer.
AB  - Extensive composite defects of the lower jaw are defined as those that involve
      skin, mandible, oral mucosa, and soft tissues. The enormous size and multilayered
      nature of these defects challenge most of the current reconstructive techniques.
      For reconstruction of extensive composite mandibular defects in 36 advanced oral
      cancer patients, two free flaps were used simultaneously in a complementary
      fashion. The aim was to provide bone reconstruction and adequate soft-tissue
      coverage in an optimal form. Primary reconstruction was carried out in 34 of 36
      cases. The fibula osteoseptocutaneous-radial forearm fasciocutaneous flap
      combination was most commonly used (n = 20), followed by the fibula
      osteoseptocutaneous-rectus abdominis myocutaneous flap (n = 11). The other
      combinations included the fibula osteoseptocutaneous-tensor fasciae latae, the
      fibula osteoseptocutaneous-rectus femoris, the iliac crest-radial forearm, and
      the iliac crest-tensor fasciae latae flaps. In 11 cases, the second free flaps
      were attached to the distal runoff of the first free flaps because of
      unavailability of recipient vessels. The mean operation time was 12 hours 10
      minutes. The complete flap survival rate was 93 percent (67 of 72 flaps) with 2.8
      percent total (2 of 72) and 4.2 percent partial (3 of 72) flap failures. Median
      follow-up time was 14 months, and 44 percent of the patients were alive at the
      time of evaluation, surviving an average of 36 months. The average survival time
      for those who died was 11.1 months. The authors believe that in selected cases
      the double free-flap procedure for one-stage reconstruction of massive mandibular
      defects is justified because it is safe and effective and improves the quality of
      life and the number of days spent outside of the hospital for these patients.

PMID- 9915163
TI  - Early decannulation with bilateral mandibular distraction for tracheostomy
      dependent patients.
AB  - Obstructive sleep apnea in the neonatal period may originate from a hypoplastic
      mandibular framework causing retroposition of the base of the tongue and an
      inadequate hypopharyngeal space. A tracheotomy in childhood is an effective
      treatment for obstructive sleep apnea, but it is associated with increased
      morbidity, management problems, and difficulties in social interaction.
      Tracheostomy-dependent pediatric patients who underwent mandibular distraction
      were reviewed to determine the effectiveness of this technique in achieving
      decannulation. A clinical review was completed to determine the status of the
      tracheostomy after external, unidirectional distraction in tracheostomy-dependent
      patients. Expansion of the mandibular framework was analyzed using traditional
      bony landmarks on predistraction and postdistraction lateral cephalograms. The
      area of the lower face was analyzed, and changes in the position of the hyoid
      bone were determined. Four patients with tracheostomies underwent an average of
      21.3 mm and 20.8 mm of distraction on the left and right hemimandibles,
      respectively. The average age at the time of distraction was 2.7 years (range,
      2.2 to 3.2 years). All patients underwent successful decannulation at an average
      of 3.8 months (range, 1.5 to 5.5 months) after completion of distraction. The
      area of the lower face increased 26.9 percent (range, 12.2 to 53.5 percent) after
      distraction, and the hyoid bone advanced an average of 14.5 mm (range, 8 to 25
      mm). Bilateral mandibular distraction is an effective method of expanding the
      mandibular framework and concomitantly advancing the base of the tongue. The
      technique provides a tool for early intervention and decannulation in pediatric
      patients with indwelling tracheostomies secondary to mandibular deficiencies.

PMID- 9915164
TI  - Endoscopically assisted mandibular subcondylar fracture repair.
AB  - The endoscope has been widely used in aesthetic surgery in recent years, but
      rarely has it been used in cases of facial trauma. From July of 1996 to December
      of 1996, the endoscope was used successfully to assist in the repair of
      mandibular subcondylar fractures in eight patients (five men and three women).
      Their ages ranged from 15 to 60 years with an average age of 31 years. Six of the
      patients had other associated mandibular fractures including angular,
      parasymphyseal, and contralateral subcondylar fractures. A 4.0-mm, 30-degree
      telescope was introduced to visualize the fracture site by means of an intraoral
      incision over the ascending ramus. A miniplate was used to stabilize the fracture
      site with the help of a percutaneous trocar. Intermaxillary fixation was applied
      for 3 to 6 days. Functionally, all patients returned to normal range of motion
      within 8 weeks. A slight deviation to the trauma site was noted on maximal
      opening in three patients, but this condition returned to normal 3 months after
      surgery. There was no facial palsy or lip numbness. The benefits of the
      endoscopic approach include not only the provision of better visualization and
      precise anatomic alignment of bony segments but also the avoidance of large
      facial scars and facial nerve injuries.

PMID- 9915165
TI  - A graduated approach to the repair of nasal septal perforations.
AB  - Septal perforation is an avoidable complication of septal surgery, but it can
      also occur because of a variety of traumatic, iatrogenic, caustic, or
      inflammatory reasons. Symptoms usually are related to disruption of the normally
      laminar flow of air through the nasal passages. Crusting, bleeding, parosmia, and
      neuralgia can develop, leading the patient to seek medical care. When local
      hygiene and conservative care are unsuccessful in relieving symptoms, closure of
      the perforation is considered. Repair is often difficult because of the limited
      exposure and limited amounts of friable mucosa with impaired vascular supply. The
      failure of attempted closure of septal perforations can be as high as 80 percent.
      The authors have developed a graduated approach to the closure of septal
      perforations that tailors the surgical approach to the size and location of the
      defect. Perforations 0.5 to 2.0 cm in size were closed in 92.9 percent (13 of 14)
      of patients using an extended external rhinoplasty approach and bilateral
      posteriorly based mucosal flaps. Larger perforations (2.0 to 4.5 cm) were closed
      in 81.8 percent (18 of 22) of patients by a two-staged technique, using a
      midfacial degloving approach to medially advance posteriorly based, expanded
      mucosal flaps. With careful preoperative management and selection of the
      appropriate surgical technique, even moderate-to-large perforations can be
      repaired reliably with limited operative morbidity.

PMID- 9915166
TI  - A retrospective study of changes in physical symptoms and body image after
      reduction mammaplasty.
AB  - Reduction mammaplasty is performed typically to alleviate the painful physical
      symptoms of macromastia. Women who suffer from macromastia also frequently
      present to the plastic surgeon with heightened body image dissatisfaction and
      maladaptive behavioral changes in response to their breast size. Numerous
      investigations have demonstrated improvement in physical symptoms after breast
      reduction surgery. Studies have also suggested that psychological improvement
      occurs postoperatively; however, they have not used well-validated, standardized
      psychological measures. The present study is a retrospective analysis of the
      physical and psychological status of women who underwent reduction mammaplasty.
      One hundred ten patients who underwent a reduction mammaplasty between 1982 and
      1996 were mailed a packet of questionnaires designed to assess current physical
      symptoms and body image. Sixty-one of the 110 patients (55 percent) responded.
      The vast majority reported substantial improvement or elimination of neck, back,
      shoulder, and breast pain, grooving from bra straps, poor posture, skin
      irritation, and social embarrassment. In addition, they reported significantly
      less dissatisfaction with their breasts as compared with a sample of breast
      reduction patients assessed preoperatively. Symptom relief and improved body
      image occurred independently of preoperative body weight, as we found few
      significant differences between obese and non-obese women concerning the
      resolution of physical symptoms or improvement in body image. Results provide
      further evidence of the efficacy of reduction mammaplasty not only for relief of
      physical symptoms but also for alleviation of body image dissatisfaction.

PMID- 9915167
TI  - Deep inferior epigastric perforator flap in breast reconstruction: experience
      with the first 50 flaps.
AB  - Abdominal wall function is a major concern for plastic surgeons performing breast
      reconstruction with TRAM flaps. The deep inferior epigastric perforator (DIEP)
      free flap spares the whole rectus abdominis muscle, includes skin and fat only,
      and therefore, preserves adequate abdominal wall competence. Between January of
      1995 and May of 1997, a total of 50 breast reconstructions in 42 patients were
      performed by using the DIEP flap. Eight patients had bilateral procedures. Five
      breast reconstructions were immediate and 45 were delayed. All patients were
      collected prospectively and no patients were excluded from this study. The
      average age of patients was 47 years (range, 22 to 59 years) and the average
      weight was 65 kg (range, 51 to 103 kg). Seventy percent of patients had one or
      more risk factors for TRAM flap reconstruction. The mean postoperative follow-up
      period was 13 months (range, 3 to 30 months). Twenty consecutive patients (17
      single and 3 bilateral DIEP flap breast reconstructions) within this group
      underwent evaluation of their abdominal wall function preoperatively and then 3
      and 6 months postoperatively by using Lacote's muscle grading system. Average
      flap harvesting time was 120 minutes and average blood loss was 420 cc. Total
      flap loss and partial necrosis occurred in one (2 percent) and three flaps (6
      percent), respectively. Abdominal wound infection occurred in seven patients (17
      percent). Unfortunately, one patient died of adult respiratory distress syndrome
      on the seventh postoperative day. Fat necrosis was found in three flaps (6
      percent). Postoperative abdominal wall examination did not reveal any hernia, but
      bulging was found in two patients (5 percent). All patients were able to resume
      their daily activities. Abdominal wall function tests in the series of 20
      patients showed that all patients had reached or even improved their preoperative
      level of upper and lower rectus muscle function 6 months after the operation. The
      external oblique muscles were the most affected by the procedure of flap
      harvesting, but only two patients (10 percent) were found to have a measurable
      impairment after 6 months. Patient satisfaction with the reconstructed breast and
      the donor site was rated high. The free DIEP flap is, therefore, a reliable and
      valuable method of breast reconstruction. The donor site morbidity was decreased,
      and the more tedious flap dissection did not affect the overall outcome.

PMID- 9915168
TI  - Endoscopic technique for harvesting the intercostal nerve as a nerve graft: a
      feasibility preliminary study in cadavers.
AB  - Endoscopic surgical procedures in plastic surgery have been applied in numerous
      aesthetic and reconstructive surgical techniques. The use of the endoscopic video
      assisted technique in peripheral nerve surgery is one of the most recent advances
      in reconstructive surgery. In this preliminary report, the seventh intercostal
      nerve, in fresh human cadavers, was harvested with the aid of endoscopy through a
      single 2-cm transverse incision. The anatomy of the intercostal nerve and the
      endoscopic surgical technique are described in this report. Multiple intercostal
      nerve grafts of adequate size, number, and length could be harvested, with less
      donor site morbidity, and used for future reconstruction of the injured
      peripheral nerve. The advantages of using an endoscopic technique to harvest the
      intercostal nerve include a magnified, clear, and illuminated visualization; a
      better remote access incision site; and an atraumatic technique, which may be
      proven particularly applicable in clinical procedures in patients who are prone
      to hypertrophic scars such as in women and children.

PMID- 9915169
TI  - Anatomic study of the distally based vastus lateralis muscle flap.
AB  - The anatomy of the vascular perforation to the distal portions of the vastus
      lateralis muscle has been studied in 20 cadaver extremities to outline the
      vascular basis for distally based vastus lateralis muscle flap. From the 15.4 +/-
      2.4, 11.8 +/- 1.7, and 7.9 +/- 2.0 cm distally to the patella, three quite large
      branches that issue from the deep femoral artery with the mean diameter of 2.8 +/
      0.2, 2.6 +/- 0.2, and 2.2 +/- 0.3 mm, respectively, distribute the distal parts
      of vastus lateralis muscle. These branches are thought to be an anatomic basis
      for the distally based vastus lateralis muscle flap. This allows the distally
      based vastus lateralis muscle flap to be raised for coverage of defects (1) in
      the popliteal fossa posterior and inferior portions of the knee anteriorly, (2)
      in the proximal one-third of the leg, and (3) for a below-knee amputation and the
      rotation of muscle tissue, such as when the gastrocnemius and soleus muscle are
      unavailable.

PMID- 9915170
TI  - Accompanying arteries of the lesser saphenous vein and sural nerve: anatomic
      study and its clinical applications.
AB  - The arteries adjacent to the lesser saphenous vein and sural nerve were
      investigated in 10 fresh cadavers that had been systemically injected with a lead
      oxide-gelatin mixture. The accompanying arteries were found to lie along the
      lesser saphenous vein and sural nerve and to nourish the skin through
      venocutaneous and neurocutaneous perforators. On the basis of the anatomy of
      these accompanying arteries, the lesser saphenous venoadipofascial (VAF) pedicled
      fasciocutaneous flap and the lesser saphenous-sural veno-neuro adipofascial (V
      NAF) pedicled fasciocutaneous flap have been developed and applied to 23 cases of
      various reconstructions of the lower extremity with proximal and distal bases.
      Survival of the flaps has been extremely good, and the flaps have been clinically
      useful.

PMID- 9915171
TI  - Routine donor leg angiography before vascularized free fibula transplantation is
      not necessary: a prospective study in 120 clinical cases.
AB  - To evaluate the value of routine preoperative angiographies of donor sites, 120
      patients with free fibula osteoseptocutaneous flap transplantations were included
      in this prospective study, which consisted of preoperative evaluation of dorsalis
      pedis and tibial posterior artery pulsation and angiographies of the donor legs
      (120 patients) and contralateral legs (111 patients). Both pedal pulses were
      palpable in 114 patients, and only one pulse was palpable in six patients. The
      respective nonpalpable foot pulses were detectable with pencil Doppler in five
      patients, but they were not detectable in one patient. Intraoperatively, the
      latter patient had a relatively hypertrophied peroneal artery as compared with
      both the tibial posterior and tibial anterior arteries. The angiographic result
      was arteria peronea magna. The other five patients showed intraoperatively and
      angiographically normal-sized major arteries of the lower leg. In three patients
      with normal pedal pulses, hypoplasias of either the tibial anterior or tibial
      posterior arteries were found intraoperatively. These findings corresponded with
      the angiographical results. In all patients (n = 119), except one with peroneal
      artery hemangioma, free osteoseptocutaneous fibula flap was harvested from the
      originally planned leg without subsequent sequelae to the respective donor leg.
      In 231 leg angiographies, only 7 cases (3 percent) with abnormalsized major lower
      leg arteries were described. The diagnoses in these cases were hypoplasia of
      either the tibial posterior or tibial anterior artery (4 cases), arteria peronea
      magna (2 cases, one of which was a false positive), absence of peroneal artery
      combined with hypoplastic tibial posterior artery (1 case), and hemangioma of the
      peroneal artery (1 case). From this prospective study, it was determined that
      routine preoperative angiography of the donor leg before fibula transplantation
      is not justified. It does not add relevant new information about donor leg
      vascularity, provided that the clinical evaluation of the pedal pulses is well
      conducted. The only two conditions that may require a preoperative donor leg
      angiography are abnormal pedal pulses or significant previous lower leg trauma.

PMID- 9915172
TI  - Evaluation of hand sensibility with single and double latex gloves.
AB  - The purpose of this study was to examine hand sensibility of surgeons wearing
      single and double latex gloves. Evaluation of hand sensibility, including
      cutaneous pressure thresholds, moving two-point discrimination, and static two
      point discrimination, was performed on 25 surgeons (mean age 45 years). The
      dominant hand index finger was assessed with no glove, single glove, and double
      glove. The majority of surgeons had a moving and static two-point discrimination
      of 2 or 3 mm. The lowest cutaneous pressure thresholds were found when measured
      with no gloves and increased with single and double gloves. Statistically
      significant differences in cutaneous pressure thresholds using Semmes-Weinstein
      monofilaments were found for gloves versus no gloves (p < 0.0003) and single
      versus double gloves (p = 0.0003). Statistically significant differences in
      moving two-point discrimination were found for no gloves versus double gloves (p
      = 0.05) and single versus double gloves (p = 0.02). In conclusion, we found
      significant differences in hand sensation when measured with single and double
      gloves.

PMID- 9915173
TI  - Donor site morbidity after suprafascial elevation of the radial forearm flap: a
      prospective study in 95 consecutive cases.
AB  - From March of 1995 to November of 1997, 95 free radial forearm flaps for
      orofacial reconstructions were performed and included in this prospective study
      of donor site morbidity. All flaps were elevated using the suprafascial
      dissection technique. Donor site closure was performed with either split
      thickness skin grafts (64 cases) or full-thickness skin grafts (31 cases). Among
      the 95 flaps, there were two complete flap losses and one partial flap loss
      because of arterial thrombosis. One orocutaneus fistula was successfully treated
      with a pedicled pectoralis major flap. At the donor site, the rate of complete
      take of skin graft was 94 percent in 95 patients. Functional and aesthetic
      results evaluated at least 6 months postoperatively in 50 patients revealed no
      significant change in grip power, pulp-to-pulp pinch power, or wrist movement in
      the complete skin graft take group (45 cases), whereas in the partial skin graft
      failure group (5 cases), both grip power and movement were significantly
      decreased. There was no remarkable cold intolerance in any of the 50 patients.
      Critical evaluations of sensory change revealed numbness distal to the donor site
      in 54 percent of the patients. However, dysesthesia was usually mild and improved
      spontaneously as time passed. Aesthetic outcome was rated as good or fair in 98
      percent of the cases. The results of this prospective study show that
      suprafascial elevation of the radial forearm flap is superior to the classic
      elevation technique, particularly with regard to a higher rate of immediate
      complete take of skin grafts, thus avoiding impairment of range of motion and
      strength of the donor hand.

PMID- 9915174
TI  - Prefabrication of bilaminar-epithelialized composite flap with tissue expander
      and cultured keratinocytes.
AB  - This study investigated the feasibility of prefabrication of a bilaminar
      epithelialized flap by using a tissue expander and cultured keratinocytes, for
      reconstruction of perforate defects in the oral cavity and upper aerodigestive
      tract. In each of six rats, a 10-ml volume expander was implanted under the
      inferior epigastric flap and a thin silicon catheter was introduced into
      periexpander space. Seven days after implantation, 10 x 10(6) cultured
      keratinocytes, isolated from inbred donor rats, were suspended in fibrin glue and
      injected into the periexpander space through the catheter (n = 4 of 6). The
      expansion was started immediately after cell inoculation and lasted at least 3
      weeks at the speed of 2 to 3 ml every 5 to 7 days. At the end of expansion, the
      periexpander space was opened and the capsule around the tissue expander was
      found to be covered completely with a neoepithelium. Thus, a bilaminar
      epithelialized flap based on femoral vessels was elevated and successfully
      transferred to cover the excisional perforate defect in the oral cavity with the
      neoepithelial side as inner lining. All flaps treated with 10 x 10(6) cultured
      keratinocytes survived with complete wound healing during a 1-week follow-up (n =
      4 of 6). Both macroscopic and histologic findings demonstrated that a bilaminar
      epithelialized composite flap can be fabricated by using a tissue expander and
      keratinocyte-fibrin glue suspension.

PMID- 9915175
TI  - Description of cutaneous excision and suture using a mathematical model.
AB  - Mathematical models are being developed at a fast rate in industry thanks to
      computer technology; they are used to simulate motion and deformation over time
      to test materials and objects in a virtual manner. These modeling techniques are
      being developed in medicine, but they remain, at this time, in the domain of
      biomechanical research. We report a mathematical model for cutaneous excision and
      suture, which we have used to predict the deformations and tensions that result
      when using four different forms of excision. The results are expressed in
      numerical and graphic form. The results obtained corresponded with our experience
      in dermatologic surgery. Uses and limits of this model are discussed.

PMID- 9915176
TI  - Decrease in adhesion formation by a single application of 5-fluorouracil after
      flexor tendon injury.
AB  - Using an animal model, the effect of a single intraoperative application of 5
      fluorouracil on digital flexor tendon adhesions was assessed. After a standard
      partial division of the tendon and immobilization with a stitch, the synovial
      sheath in 30 rabbit tendons was treated with 5-fluorouracil solution (50 mg/ml)
      soaked sponge pledgets for 5 minutes. Buffered saline was substituted for 5
      fluorouracil in 30 control tendons. The tendons were harvested 1 week
      postoperatively, and histologic sections were assessed with a light microscope.
      There was a significant reduction in synovial sheath thickening (p < 0.001), cell
      counts (p < 0.001) and proportional length of adhesions (p < 0.001) in the
      treated tendons. The reduction in synovial reaction and adhesion formation using
      this "one touch" technique presents a novel strategy for the management of the
      clinical problem of postoperative adhesions complicating tendon injury and
      repair.

PMID- 9915177
TI  - Reverse dorsal digital and metacarpal flaps: a review of 27 cases.
AB  - Reverse dorsal digital and metacarpal flaps use the dorsal skin of the digital or
      metacarpal areas, and they are based on the arterial branches anastomosing the
      volar and dorsal arterial networks of the fingers. These flaps are transposed as
      reverse island flaps. Dissection of the flap is easy, fast, and preserves the
      collateral nerve and artery to the fingertip. A series of 27 flaps is reviewed,
      with more than 6 months of follow-up. Skin defects in all patients were located
      over or beyond the proximal interphalangeal joint as far as the fingertip and
      were combined with bone, joint, or tendon exposure. The flaps we used were
      reliable, and a joint or extensor tendon reconstruction could be performed at the
      same time. Patients were discharged the day after surgery and allowed to mobilize
      the finger early. No flap necrosis was observed, and donor site morbidity was
      minimal; primary closure or a skin graft was used in all patients. These flaps
      combine the advantages of an extended skin paddle and a versatile pivot point on
      the phalanx, and they allow coverage of wide and distal defects. When
      conventional local flaps are inadequate, this fast and simple procedure should be
      considered for its reliability and low associated morbidity.

PMID- 9915178
TI  - A case of Pai syndrome.
AB  - A fourth patient suspected of having Pai syndrome is described. The female baby
      had a median cleft of the upper lip, a polypoid skin mass in the right nostril,
      and a conjunctival lipoma in the right eye. A median alveolar cleft was in the
      oral cavity. The polypoid skin mass was attached to the nasal septum, and a
      histologic examination disclosed mature adipose tissue with normal skin and no
      cartilaginous tissue. A computed tomographic scan revealed a lipoma of the corpus
      callosum. However, the patient was neurologically normal, and her
      electroencephalogram was also normal. Her growth and development have been within
      normal limits, and no convulsions have occurred.

PMID- 9915179
TI  - Stahl's ear caused by an abnormal intrinsic auricular muscle.
AB  - Stahl's ear in a 12-year-old girl was treated surgically. During the operation,
      we discovered that the transverse muscle had an abnormal course, and we concluded
      that this muscle had caused the deformity. Treatment was accomplished by
      cartilage incision and transposition of the muscle to its normal position. After
      3 years of follow-up, the reconstructed ear has maintained a good appearance. The
      etiology of Stahl's ear is unknown. Although various techniques have been
      reported for the reconstruction of Stahl's ear, the course of the intrinsic
      auricular muscles have not been confirmed by surgeons during the operation. We
      think that this case provides insight into the etiology of Stahl's ear and
      provides guidance for a new surgical treatment.

PMID- 9915180
TI  - Surgical management of penoscrotal lymphangioma circumscriptum.
AB  - Lymphangioma circumscriptum of the penis and scrotum is an unusual entity that
      may be indistinguishable from genital warts. After confirmation of the diagnosis,
      a treatment plan consisting of wide excision should be outlined. To lower the
      chance of recurrence, not only the affected skin but all the subjacent
      subcutaneous tissue, including the deeper components of the lymphatic
      malformation just above the deep fascia, should be removed.

PMID- 9915181
TI  - One-stage reconstruction of microtia in microform.
AB  - We treated five patients with auricular deformities (microtia in microform and
      group IIB or III constricted ears) using the following procedure: nearly all of
      the contralateral conchal cartilage was resected, grafted, and sutured to
      supplement a cartilaginous deficit and to keep the supporting frame of conchal
      cartilage expanded by the double banner flap method. After this, a soft tissue
      deficit was reconstructed by our newly developed method of covering the defect
      with a triangular flap superior to the auricle by making a skin incision and a
      rhomboid flap anterior to the auricle. So far, we have obtained satisfactory
      results using this one-stage procedure.

PMID- 9915182
TI  - Upper eyelid orbicularis oculi flap with tarsoconjunctival island for
      reconstruction of full-thickness lower lid defects.
AB  - The reconstruction of full-thickness defects of the lower eyelid after tumor
      resection is a challenging operation. The great number of techniques for these
      defects shows that none of them is the operation of choice. The method of
      reconstruction will be chosen according to the extent of the defect, the missing
      components of the eyelid structure, the age of the patient, and the quantity and
      the quality of the surrounding tissues. In this article, we propose, under
      specific indications, the use of a pedicled myocutaneous orbicularis oculi flap
      with a tarsoconjunctival island from the upper eyelid to reconstruct full
      thickness lower lid defects. The more choices in a surgeon's armamentarium, the
      more easily the difficult problems of periorbital surgical oncology will be
      resolved.

PMID- 9915183
TI  - Turnover forehead flap combined with composite crus of helix graft for partial
      nasal reconstruction.
AB  - Partial lateral nasal defects challenge the plastic surgeon both technically and
      aesthetically. Many methods for reconstruction of these defects have been
      described. We have used a turnover forehead flap in conjunction with composite
      auricular graft for the reconstruction of nasal defects. The forehead flap is
      turned over so that the forehead skin serves as internal lining in the nose. The
      composite auricular graft serves as external nasal lining and provides mechanical
      support to the ala. The technique was used in seven patients and is presented
      here with illustrations, selected cases, results, and conclusions concerning
      patient selection.

PMID- 9915184
TI  - The vermilion myomucosal flap for the treatment of oral commissure gunshot wound
      deformities.
AB  - The vermilion myomucosal advancement flap was successfully used to reconstruct
      the oral commissure for a wide range of deformities in three patients with facial
      gunshot wounds. In one case, a delayed cross lip flap was later used to restore
      the philtrum of the upper lip, despite the fact that the cutaneous perforating
      vessels of the cross lip flap had previously been divided.

PMID- 9915185
TI  - A simple preparation of autologous fibrin glue for skin-graft fixation.
AB  - Numerous uses of fibrin glue as a sealant, hemostatic agent, and adhesive have
      been reported. We developed a simple method of preparing autologous fibrin glue
      for skin-graft fixation. Fifty patients have undergone the autologous fibrin glue
      technique for trauma, burns, and difficult wounds. The mean area grafted was 237
      cm2 (range 50 to 700 cm2), and grafts were typically 0.012 to 0.016 inch thick
      (meshed 1.5:1). A standard gauze dressing was applied to all wounds, and no
      sutures or staples were used. At a mean follow-up of 3.4 months (range 1 to 9
      months), 45 of 50 patients had over 95 percent take, and no patient had less than
      90 percent take. There were no adverse reactions or infections noted, and no
      patient required additional grafting. This method offers a simple, cost-effective
      alternative for skin-graft fixation that leads to minimized postoperative care,
      subjectively cleaner wounds, and high patient satisfaction.

PMID- 9915186
TI  - Report of phenol peel for Asians.
AB  - With the advancement of trichloroacetic acid peel technology and wound care,
      trichloroacetic acid peeling has become very successful in Korea. Its success has
      opened studies on the possibility of using phenol on Korean skin. Dr. Mee's
      phenol formula (molding mask technique) was chosen for experiments on Korean skin
      because of the presumed safety of use on non-Caucasian skin. Between January of
      1996 and January of 1998, 30 cases of significant small pox scars were treated
      with phenol at the Korea University Anam Hospital. The age range was from 43 to
      60 years, with a mean of 49 years. The average follow-up period was 13 months,
      ranging from 1 month to 2 years. All of the procedures were performed in the
      operating room while the patient was under deep i.v. sedation. After the entire
      face was peeled, it was covered with an occlusive tape mask. During the recovery
      period, the patients underwent a post-peel skin care program. All 30 patients
      showed significant improvement of the severe pox marks with a marked rejuvenation
      effect. There was no sign of hypopigmentation or hyperpigmentation. As a
      complication, two patients developed hypertrophic scars on the perioral area,
      which responded well to steroid injections. Another pair of patients had herpetic
      infection, which left minimal scarring. Five patients developed cardiac
      arrhythmia with this rapid technique, but this was safely managed by an
      anesthesiologist during the procedure. Korean skin belongs to Fitzpatrick types
      IV and V and occasionally to type III or VI. It is common knowledge that
      performing chemical peeling on the latter types of skin is dangerous, but in this
      report, excellent results were obtained from all 30 patients, even though the
      peeling itself was very deep. With more knowledge and experience, phenol peel can
      be safely conducted on Asian skin.

PMID- 9915187
TI  - Shortening of the long forehead.
AB  - A long forehead disrupts the harmony among the facial components and may
      contribute to the semblance of facial aging. Slight forehead length disharmony on
      a senescent face can be corrected by placing the incision at the hairline,
      elevating the eyebrows through subcutaneous or subgaleal dissection, and removing
      excess skin without posterior scalp immobilization. For moderate to major
      reduction of the forehead length, the scalp is elevated back to the occipital
      region through a pretrichial incision, and relaxation incisions are made at a
      right angle to the vector of advancement. The entire scalp is then repositioned
      anteriorly, advancing the hairline caudally and shortening the forehead.
      Retraction of the scalp or excessive elevation of the eyebrows is prevented by
      anchoring the galeal fascia to the cranial bone using a bone-tunneling technique
      in one to three rows. The number of fixation rows is commensurate to the amount
      of advancement and rigidity of the scalp. The more immobile the scalp
      preoperatively, the more relaxation incisions and fixation tunnels are necessary.
      Following caudal repositioning of the scalp, the non-hair-bearing skin is
      excised, and a meticulous repair is done. These procedures have been performed in
      180 patients with a high degree of satisfaction. Temporary hair loss was
      experienced in one smoker who underwent the most advancement through posterior
      scalp elevation and continued to smoke postoperatively. Also, on three patients
      in the subcutaneous forehead rhytidectomy group, two of whom were smokers,
      delayed healing was observed in the temple area because of compromised
      circulation requiring secondary revision.

PMID- 9915188
TI  - Hairline lowering during foreheadplasty.
AB  - Many patients seeking rejuvenation of their foreheads have high hairlines and are
      troubled by the prospect that surgery will worsen the deformity. Hairline
      elevation occurs in both coronal and endoscopic foreheadplasty techniques and is
      at least part of the reason that many surgeons do not always recommend these
      procedures when otherwise indicated. Although a pretrichial "hairline" incision
      prevents hairline retro-displacement, it results in forehead shortening only and
      not true hairline lowering. When a pretrichial incision is used in combination
      with a posterior scalp advancement flap, however, true hairline lowering is
      possible. Experience with this technique encompasses 27 procedures performed over
      a 5-year period. Patients ranged in age from 35 to 71 years. A significant
      improvement was demonstrable in all cases and corresponded with a high degree of
      patient satisfaction. No serious complications were seen. A high hairline must be
      recognized as the source of both a disproportionate and aged appearance. The
      ability to lower the hairline and place it in a more proportionate, youthful
      relationship with the rest of the face adds a new dimension to foreheadplasty
      equal to or greater in importance to an overall improved appearance as other
      maneuvers typically performed during the procedure. For many patients, the
      benefits of hairline lowering far outweigh the trade-off of a more anteriorly
      situated, and possibly more visible, scar.

PMID- 9915189
TI  - Elaboration of an alternative, segmental, cartilage-sparing tip graft technique:
      experience in 405 cases.
AB  - Despite the value of tip grafting in many rhinoplasty patients, adequate donor
      cartilage may be unavailable in secondary and even primary patients whose donor
      sites have been harvested previously or whose septal cartilage is calcified.
      Furthermore, by enlarging the lobule, tip grafts can create undesirable
      postoperative disproportions in some patients. These two observations have
      stimulated the elaboration of a tip graft method (which evolved from the Sheen
      technique) that uses small amounts of autogenous donor material to augment only
      those lobular segments that require increased contour or support, without
      necessarily increasing overall lobular volume. This article reports experience
      with; the technique in a 405-patient study group. Segmental tip grafting is
      performed endonasally through access incisions along the caudal edge of one alar
      cartilage. Grafts augment each third of the tip lobule and anterior columella
      (corresponding to each of the alar cartilage crura) depending on the aesthetic
      objective; multiple grafts are always placed. Selective augmentation limits the
      overall increase in lobular size. The method is not suitable for those patients
      needing substantial augmentation (58 of 463 tip-grafted patients in the 6-year
      study period), in which case the author still prefers the Sheen technique. The
      records of the 405-patient study group (40 percent primary rhinoplasty, 60
      percent secondary rhinoplasty) indicate a total nasal revision rate of 14
      percent; 6 percent were tip revisions. Tip revisions were more frequent in
      secondary patients but not in patients with thin skin. Reoperation percentages
      decreased during the study term, so that the tip revision rate was 12 percent in
      the first 12 months of study but only 4 percent in the last 12 months (p <
      0.0008). The primary indication for tip grafting has evolved since the author's
      earlier practice experience: in the past 3 years of the study, 77 percent of
      primary patients and 80 percent of secondary patients underwent grafting
      principally to improve lobular contour, not tip projection (p < 0.0005). A
      segmental, cartilage-sparing tip graft technique can provide both projection and
      contour for primary and secondary rhinoplasty patients. Nevertheless, tip
      imperfections remain the most common reason for revision in the author's
      practice.

PMID- 9915190
TI  - Anatomic basis and clinical implications for nasal tip support in open versus
      closed rhinoplasty.
AB  - Successful rhinoplasty depends on nasal tip support and its influence on nasal
      tip projection. The factors involved in nasal tip support are numerous; however,
      the role of the anterior septum versus the lower lateral cartilages has been
      debated in the literature. The purpose of this study was to quantitate, using
      fresh cadavers, the critical elements for nasal tip support with open versus
      closed rhinoplasty techniques. Multiple nasal manipulations, including cephalic
      trim, cephalic trim and interruption of the lower lateral cartilages, dorsal hump
      resection (1 to 4 mm), submucous resection of the septum, and complete septal
      removal, were performed using fresh cadaver heads and using both the open and
      closed rhinoplasty approach. Changes in nasal tip support were recorded. In
      comparing similar procedures, the mean loss of tip projection for the open
      approach was 3.43 mm versus 1.98 mm for the closed approach (p < 0.001). There
      was a significantly larger loss of tip projection in open versus closed
      procedures for cephalic trim, cephalic trim and interruption of the lower lateral
      cartilages, and cephalic trim with interruption of the lower lateral cartilages
      and septum removal (p < 0.001, 0.001, and 0.001, respectively). We attributed the
      differences between the open and closed approaches to the increases in
      ligamentous disruption and skin undermining that occur when using the open
      approach. Septum manipulation in general resulted in larger losses in tip support
      in both the open and closed approach. We conclude that the open approach for
      rhinoplasty results in a significantly increased loss of tip projection when
      compared with the closed technique due to the larger disruption of ligamentous
      support. Contrary to previous data, septal manipulation resulted in significant
      losses of tip projection, most likely secondary to lowering the nasal septal
      angle, and this effect may be more significant in closed rhinoplasty. The
      apparent clinical implications are that active measures, such as columellar
      struts and/or suture techniques for adding or maintaining nasal tip support
      during rhinoplasty, are indicated, especially when using the open approach and
      when any anterior septal alteration is performed using the open or endonasal
      approach.

PMID- 9915191
TI  - The rate of warping in irradiated and nonirradiated homograft rib cartilage: a
      controlled comparison and clinical implications.
AB  - Irradiated homograft costal cartilage reportedly warps less than autologous
      cartilage based on clinical observation; however, no controlled, experimental
      studies on the warping characteristics of irradiated homograft costal cartilage
      have been done. Fresh cadaver costal cartilage (ribs 5 through 8) was prepared
      and irradiated using a standardized technique. A specially designed cartilage
      cutting device was used to cut the cartilage into a reproducible size. The
      irradiated (n = 23) and nonirradiated (n = 20) groups were incubated in vitro and
      assessed over a 4-week period. There was no significant difference in warping
      between the irradiated and nonirradiated groups (p = 0.1). The centrally cut
      pieces of cartilage in each group warped less than peripherally cut blocks in
      each group. Peripherally cut pieces of both the irradiated and nonirradiated
      groups warped at a faster rate compared with the nonirradiated groups. All
      cartilage exhibited continued warping over the 4-week study period. We concluded
      that there was no difference in warping characteristics between irradiated and
      nonirradiated homograft rib cartilage. Furthermore, unlike previous studies,
      cartilage grafts continued warping over time for at least 4 weeks, and this
      phenomenon may be extrapolated as a causative factor in delayed postoperative
      nasal deviation after rhinoplasty and nasal reconstruction where rib grafts are
      used.

PMID- 9915192
TI  - Limited incision foreheadplasty.

PMID- 9915193
TI  - Giant liponecrotic pseudocyst after breast augmentation by fat injection.
AB  - A case in which a growing and painful mass developed in the breast 10 months
      after fat injection following trochanteric and abdominal liposuction is
      described. Treatment included lumpectomy and breast reconstruction in a second
      stage by bilateral subpectoral augmentation mammaplasty with textured gel-filled
      prostheses. Histologic examination revealed a liponecrotic pseudocyst. The
      development of pseudocysts and microcalcifications after breast autologous fat
      injection is a complication that warns against using this technique for breast
      augmentation.

PMID- 9915194
TI  - Carbon dioxide laser-assisted endoscopic forehead lift.

PMID- 9915195
TI  - Controversies in the management of inferior turbinate hypertrophy: a
      comprehensive review.
AB  - Nasal obstruction must frequently be addressed during functional rhinoplasty.
      Even after a properly performed septorhinoplasty correcting septal deflection
      and/or nasal valve collapse, nasal obstruction may persist due to turbinate
      hypertrophy. Turbinates have many important functions, including warming and
      humidification of inspired air, and numerous factors can contribute to pathologic
      enlargement. Management of inferior turbinate hypertrophy has been actively
      debated for more than a century. The primary goal of therapy is to maximize the
      nasal airway for as extended a period as possible while minimizing complications
      of therapy, such as nasal drying and hemorrhage. This review describes the
      various medical and surgical therapeutic modalities widely used today, with
      emphasis placed on surgical management of the inferior turbinates. Advantages,
      disadvantages, complications, and controversies of each form of treatment are
      reviewed and discussed. A staged protocol of increasingly invasive interventions
      is proposed.

PMID- 9915196
TI  - The use of perioperative corticosteroids in craniomaxillofacial surgery.
AB  - A literature search could not identify a study on the prevalence of the use of
      perioperative corticosteroids by surgeons performing craniomaxillofacial surgery.
      To gather this information, we conducted a survey of North American members of
      the American Society of Maxillofacial Surgeons classified as "active" in the
      society's roster. The first 90 members in forward and reverse alphabetical order
      who were capable of receiving a fax transmission were faxed our survey. Sixty
      surgeons responded, for a response rate of 66.7 percent. Twenty-eight (46.7
      percent) reported using short-term, high-dose, perioperative corticosteroids to
      control postsurgical inflammation. Surgeons performing facial aesthetic surgery
      alone or in addition to craniomaxillofacial surgery were more likely to be using
      steroids (Fisher's exact test, p = 0.038). A variety of steroid drugs and
      regimens were cited by steroid users. The most common reason for using steroids
      was to decrease edema. Thirty-two (53.3 percent) responders reported that they
      were not using steroids. The most common reason for not using them was a lack of
      literature to support their effectiveness. All responders were asked to report
      any complications encountered with the use of steroids. The majority (78.3
      percent) reported no complications. The most common complication encountered was
      euphoria (13.3 percent). No one reported the occurrence of avascular necrosis of
      the hip or humerus with the use of steroids. Based on a literature review, an
      analysis of the steroid regimens and complications reported revealed that steroid
      use was generally safe. Nevertheless, in addition to the traditional steroid
      contraindications, consideration should be given to withholding steroids in
      patients with any of the known risk factors for avascular necrosis, in patients
      who are or recently have been on nonsteroidal anti-inflammatory drugs, and in
      aspirin-sensitive asthmatics. These patients may be at increased risk for serious
      adverse effects with the use of steroids. More research is required to
      objectively measure the effect of steroids on edema and, if beneficial, to
      determine the optimal drug regimen.

PMID- 9915197
TI  - Pediatric facial fractures: who should treat what, and how?

PMID- 9915198
TI  - Pediatric facial fractures: who should treat what, and how?

PMID- 9915199
TI  - Blepharoptosis repair by selective use of superiorly based muscle flaps.

PMID- 9915200
TI  - Closure of centrally located defects of the ear.

PMID- 9915201
TI  - A simple technique for mucosal irregularities of the lip.

PMID- 9915202
TI  - Effects of the geniohyoid muscle impairment in tongue injury with mandibular
      fracture.

PMID- 9915203
TI  - Regional anesthetic technique for the face.

PMID- 9915204
TI  - Mastopexy after explantation.

PMID- 9915205
TI  - Is "predetermined design" different from "high lateral tension abdominoplasty?".

PMID- 9915207
TI  - Safe carpal tunnel release with a palmar incision.

PMID- 9915206
TI  - A historical review of preputial restoration.

PMID- 9915208
TI  - An 18-year follow-up and late debulking of an intercostal free flap to the lower
      leg stump.

PMID- 9915209
TI  - "Sure-closure" skin stretching system.

PMID- 9915210
TI  - Flaps that should not be used in plantar ulcers in leprosy.

PMID- 9915211
TI  - Burn depth estimation: use of laser doppler flowmetry.

PMID- 9915212
TI  - A burn from a plant.

PMID- 9915213
TI  - Is heat shock protein a potential protective mechanism against ischemia
      reperfusion injury?

PMID- 9915214
TI  - Evaluation of skin flap survival in rats.

PMID- 9915215
TI  - Biocompatibility of Artecoll.

PMID- 9915216
TI  - Tinea corporis with secondary impetigo associated with silicone gel sheeting.

PMID- 9915217
TI  - Effect of cooling the wetting solution on cavitation in simulated ultrasound
      assisted lipoplasty environment.

PMID- 9915218
TI  - Automatic syringe.

PMID- 9915219
TI  - Workforce issues.

PMID- 9915220
TI  - Polymorphisms of coagulation factor genes--a review.
AB  - Common genetic variants of coagulation factor genes associated with differences
      in concentration and/or function of coagulation factors have been studied in
      search of variability that could explain the individual susceptibility to
      thrombosis and atherothrombotic diseases. The more outstanding polymorphisms in
      genes of factors involved in coagulation and fibrinolysis described in the
      literature (such as fibrinogen, factor XIII, glycoprotein IIb/IIIa, von
      Willebrand factor, factors VII, VIII and IX, factor V, ATIII and protein C system
      factors, prothrombin, PAI-1 and fibrinolytic system) are reviewed in the context
      of factor's structure and function and also in its proposed relevance for
      thrombotic and atherothrombotic risk definition.

PMID- 9915221
TI  - Urinalysis--challenges by new medical needs and advanced technologies.

PMID- 9915222
TI  - The automation of sediment urinalysis using a new urine flow cytometer (UF-100)
AB  - The UF-100 analyser is a fully automated instrument that stains the DNA and the
      membranes of the formed elements in native urine. The sample then passes as a
      laminar flow through a laser beam and light scattering, fluorescence and
      impedance are measured. The main purpose of the present work was to assess the
      analytical performance and the accuracy of the measurements of the UF-100
      analyser. No carryover was observed, while the linearity was higher then the
      upper limit (40000 total particles microl(-1)) suggested by the manufacturer. The
      within-run imprecision was low, ranging from 17.7 % to 2.4% and was up to
      threefold better than manual microscopy. Comparison of results obtained by
      sediment microscopy (performed according to National Committee for Clinical
      Laboratory Standards (NCCLS) recommendations) and by the UF-100 analyser showed a
      linear correlation with r = 0.833 for erythrocytes, r = 0.934 for leukocytes, r =
      0.880 for epithelial cells and r = 0.40 for casts. To evaluate the reliability of
      the UF-100 analyser in detecting bacteria we compared the results with the
      microbial culture (n = 608). Using a cut-off value of bacterial count above 1800
      degrees l(-1) and at leukocyte count above 45 microl(-1), the analyser detected
      positive cultures with a sensitivity of 87 % and a specificity of 80 %. In
      conclusion, the UF-100 analyser can improve the work flow, increasing the output
      of urinalysis by reducing the number of specimens submitted for microscopy. Also
      the method provides reliable information for the identification of urinary tract
      inflammation and bacterial infection.

PMID- 9915223
TI  - Urinary microscopy as seen by nephrologists.
AB  - Urinary microscopy is a diagnostic tool which is largely used by nephrologists.
      In the opinion of the authors the best results can be achieved when all the
      aspects concerning this test are properly taken into account. Thus, from the
      methodological point of view, proper patient guidance, proper urine collection
      and handling, adequate microscopic equipment, and knowledge of the factors which
      can influence the results are all necessary. All the elements of clinical
      importance have to be known, namely, erythrocytes (with their morphological
      subtypes), leukocytes, tubular cells, uroepithelial cells (both superficial and
      deep), lipids, casts, crystals, and microorganisms. Then, the urinary findings
      have to be interpreted and, whenever possible, also combined into urinary
      profiles (e.g., the nephritic sediment, the nephrotic sediment). This, combined
      with other laboratory tests, the pathologic findings, and the clinical data,
      allows for the definition and management of urinary tract diseases.

PMID- 9915224
TI  - Measurement of urine relative density using refractometer and reagent strips.
AB  - The relative density of urine is the ratio of its density to that of water and
      depends on both the number and weight of solute particles in the sample, while
      osmolality depends only on the number of solute particles. Water metabolism is
      regulated by the interaction of the renal medullary countercurrent system with
      the circulating levels of antidiuretic hormone and thirst. The concentration of
      solids in urine can be measured by weighing, hydrometry, oscillations of a
      capillary tube, refractometry and reagent strip. These techniques, interrelated
      but not identical, are commonly used in hospital laboratories and in clinical
      wards. We compared the results obtained in 1725 urine samples of inpatients and
      outpatients using an automated refractometer to those obtained using two visually
      read dip stick tests. The correlation coefficients (Super Aution analyser vs.
      Aution Sticks 10EA, Aution Sticks 10 EA vs. N-Multistix, Super Aution analyser
      vs. N-Multisticks were 0.663, 0.645 and 0.514, respectively) and the great
      dispersion of mountain plots demonstrates that different techniques are not
      interchangeable in the measurement of relative density. Since the results
      obtained after discarding the samples with pH higher than 7 and those containing
      glucose or protein were very similar to the ones reported above, the role of
      these interferents appears negligible in inducing the discrepancy.

PMID- 9915225
TI  - Dry chemistry urinalysis of pathological proteinuria.
AB  - The paper presents a review of the characteristics and analytical performance of
      the most current dry chemistry methods for detection and estimation of the
      different urinary proteins. Description of the classical "protein error"
      dipsticks for macroalbuminuria is supplemented by data on more sensitive
      alternatives based on the same principle, reaching into the zone of
      microalbuminuria. Immunological test strips are available for detection of low
      concentrations of albumin. Application of the same principle is attempted for
      detection of other specific proteins. Highly sensitive enzymatic reactions allow
      detection of "lysis proteins": haemoglobin, leukocyte esterase and beta-N-acetyl
      glucosaminidase. An efficient strategy for screening for all types of
      pathological proteinuria based on detection of low albumin levels is presented.

PMID- 9915226
TI  - Physiopathology of proteinuria and laboratory diagnostic strategy based on single
      protein analysis.
AB  - A quantification of proteins of different molecular size has been shown to be
      useful in characterizing the mechanism and medical causes of proteinuria. By
      analyzing urine albumin, alpha1-microglobulin, immunoglobulin G and alpha2
      macroglobulin together with total protein, prerenal, glomerular, tubular and
      postrenal causes of proteinuria can be detected and differentiated by their
      specific urine protein patterns. Using automated turbidimetric procedures,
      prerenal proteinurias are characterized by an albumin/total protein ratio below
      0.4. Tubulo-interstitial diseases which are negative in the protein test strip
      procedure are detected and clearly differentiated from other causes of
      proteinuria by their high alpha1-microglobulin/albumin ratios. In post-renal
      proteinuria, alpha2-macroglobulin proved to be a useful marker, when albumin
      excretion exceeds 100 mg/l urine. This protein exhibits plasma-like ratios to
      albumin in postrenal causes, whereas it is much lower in renal proteinurias. The
      new strategy, which has been evaluated in more than 500 clinically and partly
      histologically proven cases of renal diseases, more sensitively detects
      glomerular and tubulo-interstitial diseases when applied in urine screening and
      allows us to distinguish all clinically important causes from analysis of a
      morning spot urine sample.

PMID- 9915227
TI  - Microalbuminuria in diabetes.
AB  - Microalbuminuria is still the only early abnormality of the diabetic kidney that
      has an established prognostic value. Microalbuminuria evolves into clinical
      nephropathy and renal failure in a majority of cases of insulin-dependent
      diabetic patients, and is defined by the detection of urinary albumin excretion
      rates of 20-200 microg/min in timed urine collections. The occurrence of
      microalbuminuria at rates of 5-27 % of non-proteinuric patients and cost-benefit
      considerations justify the screening for microalbuminuria in diabetic outpatient
      clinics. Both near-normalisation of glycaemic control and treatment with ACE
      inhibitors are indicated in patients with insulin-dependent diabetes to correct
      the progression of micro- to macroalbuminuria. Other therapeutic perspectives are
      being considered, but the current notion that the available therapies may not
      arrest the course of nephropathy at this stage suggests that earlier
      interventions may be required. Prevention of microalbuminuria and overt
      nephropathy may require a primary approach to the subset of patients with a
      genetic predisposition to this complication, and several studies (candidate gene
      or genomic scan with microsatellite probes) now address the chromosomal loci and
      the nature of the genes that may be involved.

PMID- 9915228
TI  - European multicentre evaluation of the Super Aution SA-4220 urinalysis analyser.
AB  - A multicentre evaluation of the urine test strip analyser Super Aution-4220 was
      carried out in six laboratories. The analytical performance of the instrument
      with regard to imprecision, linearity, detection limit, drift, carry-over and
      method comparison was studied. Using the Aution stick 8 test strip the pH,
      glucose, protein, ketones, bilirubin, blood, urobilinogen and leukocyte esterase
      were analysed. Specific gravity measurements were performed by refractive index
      method. Within-run and between-run imprecision determined at three levels of
      analyte were good. No carry-over was observed. Obtained results were linear
      through all the described analytical range. No significant drift was detected.
      Method comparison with some quantitative methods was performed and showed a good
      correlation with most of the analytes. The study of interferences showed minor
      interferences by common therapeutic drugs with the measurement of some analytes.
      During the assessment period of about 6 months no breakdown occurred in any
      laboratory. The Super Aution urine analyser appeared to be a highly automated
      analyser of urinary test strips. The operation was simple and the maintenance
      required only a few minutes a day.

PMID- 9915229
TI  - Optimized detection of DNA point mutations by double gradient denaturing gradient
      gel electrophoresis.
AB  - Denaturing gradient gel electrophoresis displays the highest detection rate among
      mutation scanning methods. In classical denaturing gradient gel electrophoresis
      the denaturant gradient range and migration times vary for every amplicon to be
      scanned, greatly affecting the routine application of the method. As an
      alternative, we developed double gradient denaturing gradient gel electrophoresis
      where a gradient of pore size is superimposed over the denaturing one, allowing
      maintenance of the zone-sharpening effect even over prolonged time runs, and
      adoption of identical run time conditions for all fragments analyzed. Here double
      gradient denaturing gradient gel electrophoresis has been applied to the analysis
      of a number of point mutations and polymorphisms located in several exons of
      three different genes, the cystic fibrosis transmembrane conductance regulator,
      the beta-globin and the p53 genes.

PMID- 9915230
TI  - Is the association of serum lipase with beta2-microglobulin or C-reactive protein
      useful for establishing the diagnosis and prognosis of patients with acute
      pancreatitis?
AB  - In the Emergency Department it is mandatory to establish the diagnosis and the
      prognosis of acute pancreatitis as soon as possible. To evaluate whether the
      association of serum lipase either with serum beta2-microglobulin or with C
      reactive protein allows simultaneously to establish the diagnosis and the
      prognosis of acute pancreatitis, 96 patients with acute abdomen were studied.
      Fifty-eight patients had non-pancreatic acute abdomen and the remaining 38 had
      acute pancreatitis: 23 mild acute pancreatitis, and 15 severe acute pancreatitis.
      Forty healthy subjects were studied as controls. Lipase, beta2-microglobulin and
      C-reactive protein were determined in the serum of all subjects, using commercial
      kits. One patient with acute pancreatitis was not correctly classified when
      lipase was used to discriminate between patients with non-pancreatic acute
      abdomen and those with acute pancreatitis. For the discrimination of patients
      with severe acute pancreatitis from those with the mild form of the disease in
      the remaining 37 acute pancreatitis patients, beta2-microglobulin had a
      sensitivity of 53.3 %, specificity of 81.8%, and prognostic accuracy of 70.3 %
      (27 of the 37 patients correctly classified); 87.5 % of the 96 cases were
      correctly classified. C-reactive protein showed a lower prognostic accuracy than
      beta2-microglobulin: sensitivity 86.7%, specificity 45.5%, accuracy 62.2 %; 84.4
      % of the cases were correctly classified. Using the polychotomous logistic
      regression analysis we found the same accuracy in discriminating between patients
      with acute pancreatitis and those with non-pancreatic acute abdomen (99.0%) but a
      lower accuracy (54.1%) between patients with severe acute pancreatitis and those
      with the mild form of the disease. Our study shows that the association of serum
      lipase with beta2-microglobulin or with C-reactive protein is not useful in
      simultaneously establishing the diagnosis and prognosis of acute pancreatitis.

PMID- 9915231
TI  - Analytical and clinical performance of an automated immunoassay system (Immulite)
      for estradiol in serum.
AB  - The analytical and clinical performance of a commercial automated immunoassay
      system (Immulite) for estradiol (E2) in serum was evaluated. The functional
      sensitivity for E2 was 0.07 nmol/l, and analytical imprecision (<13%, <9% and <7%
      at 0.22, 0.51 and 1.51 nmol/l, respectively) for concentrations above this
      detection limit met published analytical goals. The assay recovery was good and
      the assay was linear over a wide concentration range. No sample carryover was
      found, and interferences from common substances present in serum were observed
      only at very high concentrations. Most of samples from men and postmenopausal
      women showed E2 concentrations below the detection limit. Longitudinal estradiol
      profiles from 11 healthy menstruating women showed characteristic menstrual cycle
      patterns (12 samples per subject obtained during a 30-day period). Longitudinal
      studies on women during induction of ovulation showed that E2 concentrations are
      highly correlated with the total number of follicles. Our results demonstrate the
      reliability of this system for routine use in the clinical laboratory.

PMID- 9915232
TI  - Evaluation of the activated partial thromboplastin time (APTT) sensitivity to
      heparin using five commercial reagents: implications for therapeutic monitoring.
AB  - Heparin is an effective drug for prevention and treatment of thromboembolic
      conditions. Although several biological assays have been proposed for monitoring
      unfractionated heparin therapy, the measurement of the activated partial
      thromboplastin time (APTT) is the most widely employed test, and the overall risk
      of thromboembolic episodes was markedly reduced by maintaining APTT ratios above
      1.5. However, the adjustment of the heparin therapy on the basis of APTT presents
      several questions which are still unresolved. Major discrepancies were found in
      APTTs performed using different reagents in both ex vivo and in vitro heparinized
      samples and occasionally with different lots of the same reagents; poor
      correlation was observed between APTT values and plasma heparin concentrations.
      In order to gain further insights into this phenomenon, we analysed the
      sensitivity to heparin of five commercial reagents for APTT measurement in 19 ex
      vivo heparinized samples. Differences were observed; correlation coefficients
      ranged from 0.820 to 0.985 and slopes of linear regressions from 0.26 to 1.14.
      Moreover, unsatisfactory correlations were obtained when APTT ratios were
      compared with heparin plasma concentrations in the same patients' samples. In the
      heparin therapeutic range of 0.35 - 0.70 U/ml, reagent-dependent differences were
      observed in the corresponding APTT values. These results point out a critical
      role of the assay methodology in monitoring heparin therapy by APTT. We suggest
      that reference materials and methods should be urgently identified, a universally
      agreed scale for reporting results should be established and reference ranges for
      the unfractionated heparin therapy should be reconsidered taking on account the
      reagent employed.

PMID- 9915233
TI  - An alternative analysis for crossover studies that accounts for between-group
      disparities in drug response.

PMID- 9915234
TI  - Perceived value of the American Board of Surgery certificate: a survey of 2,000
      Fellows of the American College of Surgeons.
AB  - BACKGROUND: This study was undertaken to identify perceptions of surgeons of the
      value of the American Board of Surgery (ABS) certificate. STUDY DESIGN: Two
      thousand Fellows of the American College of Surgeons received a 30-item survey
      designed to identify their demographics and their assessments of the functional
      and financial value of the certificate. Functional value was assessed using a 5
      point scale in the areas of professional recognition, personal satisfaction,
      court proceedings, job security, mobility, and advancement, whether the
      certificate was necessary to obtain an academic or a clinical position, and
      whether it served as an indicator of depth or breadth of surgical knowledge or of
      clinical competence. Perceived professional lifetime financial value of the
      certificate was also assessed. RESULTS: Return response rate was 37.2%. The ABS
      certificate was perceived to be most valuable in obtaining an academic or a
      clinical position and playing a significant role in court proceedings. It was
      perceived as least valuable in indicating breadth of knowledge and clinical
      competence. Sixty-seven percent responded that certified surgeons should earn
      more, and 49% estimated the certificate's lifetime financial value as more than
      $500,000. Sixty-two percent of surgeons approved of continuing the
      recertification process every 10 years. CONCLUSIONS: The ABS certificate is
      perceived as an objective credentialing instrument that affords diplomates power,
      status, an opportunity to obtain an academic or clinical position, job mobility,
      protection in court proceedings, and greater income. Although it is perceived as
      an instrument that could aid a career, it is not viewed as an indicator of a
      person's clinical competence.

PMID- 9915235
TI  - Defunctioning loop ileostomy: a prospective audit.
AB  - BACKGROUND: Defunctioning loop ileostomies are uncommonly used forms of fecal
      diversion. The aim of this study was to determine the morbidity associated with
      both construction and reversal of loop ileostomies. STUDY DESIGN: An analysis was
      performed of all patients who underwent loop ileostomy construction or reversal
      between 1990 and 1997, with data being collected prospectively. RESULTS: One
      hundred-two patients, (43 male, 59 female) with a mean age of 38 years (range 13
      to 81 years) had loop ileostomies constructed. Indications for ileostomy
      construction included inflammatory bowel disease (76 patients), ultralow anterior
      resection for carcinoma (16 patients), or miscellaneous reasons (10 patients).
      Nine patients (9%) had complications arising from ileostomy construction
      including 4 parastomal infections, 3 high output ileostomies, 1 small-bowel
      obstruction, and 1 ileostomy stenosis in the early postoperative period. Only the
      stricture required surgical intervention. All other complications improved with
      conservative management. Mean time to ileostomy reversal was 120 days. Three
      patients (4%) had complications associated with reversal. All of these
      complications required surgical intervention, 2 for small bowel obstruction, and
      1 for small bowel perforation. Currently 84 patients have had their ileostomy
      reversed, and 12 patients have had their loop ileostomy converted to a permanent
      stoma for reasons not related to the loop ileostomy itself. CONCLUSIONS:
      Defunctioning loop ileostomy is associated with low morbidity. We recommend a
      defunctioning ileostomy as the procedure of choice for temporary fecal diversion.

PMID- 9915236
TI  - Cutaneous burn increases apoptosis in the gut epithelium of mice.
AB  - BACKGROUND: Gut mucosal homeostasis depends on a balance between cell
      proliferation and cell death. After cutaneous burn injury, gut mucosal weight has
      been shown to decrease. This decrease in weight was paradoxically associated with
      an increase in gut proliferative factors. For mucosal weight to decrease in the
      presence of increased proliferation, there must be an even greater increase in
      cell death. We postulate that cutaneous burn injury causes an increase in gut
      epithelial cell death primarily by apoptosis. STUDY DESIGN: We produced a 30%
      full-thickness scald burn in the dorsum of anesthetized male C57BL6 mice and
      collected the proximal small bowel at 12, 24, 36, 48, and 60 hours after injury.
      Sham burned animals served as controls. Apoptosis and proliferation were measured
      by immunohistochemical assays (terminal deoxyuridine nick-end labeling for
      apoptosis and proliferative cell nuclear antigen assay for proliferation).
      Apoptosis was also measured by ELISA for cytoplasmic histone-associated DNA
      fragments. Mucosal height was determined on histologic sections. The two groups
      were compared at each time point using Wilcoxon two-sample test and t-test with
      Bonferroni's correction where appropriate. RESULTS: The percentage of apoptotic
      cells (number of cells stained by terminal deoxyuridine nick-end labeling per 100
      villus cells) was significantly higher at 12, 24, and 48 hours after injury. This
      increase was corroborated by an increase in the ELISA at 12 hours. Proliferation
      as measured by immunostaining for proliferative cell nuclear antigen
      significantly increased at 12, 24, 48, and 60 hours. Mucosal height as a gross
      measure of mucosal atrophy was not different between the groups. CONCLUSIONS: We
      have shown an increase in apoptosis coupled with an increase in proliferation
      after a burn injury. These results imply an increase in cell turnover in the gut
      epithelial cells after a burn. Impaired bowel function has been demonstrated
      repeatedly after burn injury, and this increase in cell turnover may be related.

PMID- 9915237
TI  - Predicting the likelihood of residual disease in women treated for ductal
      carcinoma in situ.
AB  - BACKGROUND: To identify women at risk for residual disease after excision of
      ductal carcinoma in situ (DCIS), we assessed the relationship between
      characteristics of the initial biopsy and the presence of residual DCIS at a
      subsequent operation. STUDY DESIGN: We identified 134 consecutive "paired"
      operations from 112 women who had undergone 2 or more operations for DCIS between
      February 1995 and December 1996. Cancer status of the margins, patient age and
      leading presentation, tumor subtype and grade, and the presence of multifocal
      extensive disease were assessed as potential predictors. RESULTS: Residual DCIS
      was found in 60 patients (45%): in 2 of 12 patients (17%) with negative margins,
      in 11 of 36 (31%) with close margins (< 2 mm), in 30 of 52 (58%) with positive
      margins, and in 17 of 34 patients (50%) with margins of unknown status. Patients
      with positive or unknown margins were 7.7 and 8.3 times, respectively, more
      likely to have residual disease than patients with negative margins (95% CI 1.1
      59.1; 1.1-66.4). Patients with clinical presentations were 8.0 times more likely
      to have residual disease than patients who presented with abnormal mammograms
      (95% CI 2.3-27.6). Multifocal-extensive DCIS was associated with residual disease
      (adjusted odds ratio [OR] = 7.7, 95% CI 2.9-20.5), as was comedo subtype (OR =
      2.7, 95% CI 1.1-6.7). CONCLUSIONS: Positive or unknown biopsy margins, a clinical
      presentation, multifocal-extensive cancer, and the comedo subtype are associated
      with higher risk of residual DCIS.

PMID- 9915238
TI  - Gastric cancer in young patients.
AB  - BACKGROUND: Delayed diagnosis, a high rate of histologically undifferentiated
      types of tumors, and rapid disease progression are frequently cited as the main
      reasons for the poor prognosis of gastric cancer in young patients. An improved
      prognosis has been anticipated for young gastric cancer patients because of
      recent improvements in digestive tract diagnostic techniques. This retrospective
      study was designed to determine whether these trends have had an impact on young
      Japanese patients with gastric cancer, and to further elucidate differences in
      clinicopathologic features between elderly and young patients. METHODS: From 1984
      to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of
      these, 86 patients (5.2%) were less than 40 years of age (young group). The
      clinicopathologic features of this young group were reviewed retrospectively,
      using hospital records, and compared with those of older patients (n = 499
      [29.4%], 60 to 69 years of age). RESULTS: The young group contained significantly
      higher percentages of female patients, epigastric pain symptoms, depressed
      superficial type lesions, mucosal invasion, and poorly differentiated histology;
      percentages of hepatic metastasis and venous invasion were lower. Survival rates
      for all patients and for the resected cases were significantly better in the
      young group (p = 0.035 and 0.017 respectively). The percentage of early stage
      stomach cancers for the group less than 40 years of age was 49.0% in 1984-89, but
      had risen to 60.9% by 1990-95. CONCLUSIONS: Early diagnosis has improved the
      prognosis of young gastric cancer patients. Furthermore, these data show a recent
      shift in stage distribution; additional prognostic improvement is anticipated for
      young patients with early gastric cancer.

PMID- 9915239
TI  - Total gastrectomy with extended lymphadenectomy for "curable" stomach cancer:
      experience in a non-Japanese Asian center.
AB  - BACKGROUND: Gastrectomy with extended lymphadenectomy is the advocated treatment
      in Japan for patients with "curable" stomach cancer. Attempts in units elsewhere
      adopting this approach failed to show any survival advantage, and the high
      operative mortality has prevented global acceptance of the operation. This study
      examines the safety and efficacy of radical gastrectomy in a Far East center
      outside Japan. STUDY DESIGN: A consecutive series of 121 patients with gastric
      cancer who fulfilled criteria for radical surgery had total gastrectomy with
      extended lymphadenectomy equivalent to D3 dissection over a 6-year period in a
      single unit. RESULTS: The operation carried a morbidity of 50%, with a
      perioperative mortality of 5%. Survival was best predicted by tumor stage: 5-year
      survival for patients with intact gastric serosa was 64%, versus 10% for those
      with serosal penetration (p < 0.001). The majority of documented metastases
      occurred by transperitoneal route in serosa-positive patients, but via the
      hematogenous mechanisms in those who were serosa-negative. CONCLUSIONS: Radical
      gastrectomy with extended lymphadenectomy carries high operative morbidity.
      Increased mortality occurred because of loco-regional recurrence in patients with
      T3/T4 diseases. Novel approaches including neoadjuvant treatment or regional
      therapy should be explored.

PMID- 9915240
TI  - Liver resection for metastatic colorectal cancer: assessing the risk of occult
      irresectable disease.
AB  - BACKGROUND: Liver resection is standard therapy for selected patients with
      metastatic colorectal cancer. Extrahepatic metastases and inability to remove all
      hepatic disease usually preclude curative resection and are the most common
      contraindications. This study analyzes irresectability in patients considered to
      have resectable disease taken to operation for potentially curative hepatic
      resection. We describe preoperative factors associated with irresectability and
      propose a preoperative scoring system that identifies patients at particularly
      high risk for occult irresectable disease. STUDY DESIGN: Patients considered to
      have resectable hepatic colorectal metastases were identified from a prospective
      database. Intraoperative findings that precluded liver resection were recorded.
      Demographic data, characteristics of the primary tumor, and characteristics of
      the hepatic metastases were recorded and analyzed. RESULTS: From April 1992
      through July 1997, 416 patients were explored with the intention of performing a
      potentially curative liver resection; 329 (79%) were resected. Eighty-seven
      patients (21%) had apparently resectable tumors on preoperative imaging but
      irresectable disease at laparotomy. Forty-four patients (51%) had irresectable
      disease limited to the liver; 32 had extensive bilobar disease not appreciated
      before surgery, and 12 were not resected for technical or other reasons unrelated
      to disease extent. Forty-three patients (49%) had extrahepatic disease, 31 of
      whom had resectable hepatic tumors. Of the several preoperative factors analyzed,
      only the estimated number of hepatic tumors was an independent predictor of
      irresectable findings at operation. This held true for patients with extrahepatic
      metastases and those with extensive hepatic disease. From these data, we devised
      a preoperative scoring system that estimates the probability of finding occult
      irresectable disease. Resectability ranged from 95% in patients with a score of 0
      (solitary, unilobar) to 62% in those with a score of 3 (multiple, bilobar; p =
      0.0001). The predictive value of this scoring system was then validated by
      applying it prospectively to an additional group of 118 patients taken to surgery
      for resection; the results were similar. CONCLUSIONS: Standard preoperative
      investigations predicted resectability in 79% of patients with hepatic colorectal
      metastases. Unresectable disease limited to the liver and extrahepatic disease
      were seen with nearly equal frequency. The majority of patients with extrahepatic
      metastases had resectable hepatic disease (31 of 43, 72%). A preoperative scoring
      system is proposed that identifies patients at high risk for unrecognized
      irresectable disease and may help focus the use of additional diagnostic
      modalities such as laparoscopy and positron emission tomography (PET).

PMID- 9915242
TI  - Certification by the American Board of Surgery: the task ahead.

PMID- 9915243
TI  - Ethical guidelines in surgical patient care.

PMID- 9915241
TI  - Protective role of nitric oxide in ischemia and reperfusion injury of the liver.
AB  - BACKGROUND: The suppressed production of nitric oxide (NO), associated with
      endothelial dysfunction, is thought to be a cause of ischemia and reperfusion
      injury of the liver. But findings of the salutary effects of NO enhancement on
      such injury have been conflicting. In this study, we tested our hypothesis that
      NO enhancement would attenuate ischemic liver injury. For this purpose, an NO
      precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour
      total hepatic vascular exclusion model in dogs. STUDY DESIGN: L-arginine was
      administered IV at a dose of 100 mg/kg twice (n = 5), while 300 mg/kg twice of
      FK409 was infused continuously into the portal vein (n = 5). The drugs were given
      to the animals for 30 and 60 minutes before and after ischemia, respectively. Non
      treated animals were used as the control (n = 10). Two-week survival, systemic
      and hepatic hemodynamics indices, liver function tests, energy metabolism, and
      histopathology were analyzed. RESULTS: Both treatments comparably augmented
      hepatic tissue blood flow, decreased liver enzyme release, and increased high
      energy phosphate restoration during the reperfusion period, all of which
      contributed to rescuing all of the treated animals from the 2-hour total hepatic
      ischemia. In contrast, ischemia caused 70% mortality in the control group.
      Histologically, structural abnormality and neutrophil infiltration were markedly
      attenuated by the treatments. Systemic hypotension was observed in the animals
      treated with FK409, however. CONCLUSIONS: Our data demonstrate that NO
      enhancement alleviates the liver injury caused by ischemia and reperfusion. The
      supplementation of L-arginine, rather than FK409, is considered more applicable
      to clinical use because of the absence of systemic adverse effects.

PMID- 9915244
TI  - A new technique of Hepp-Couinaud hepaticojejunostomy using the posterior approach
      to the hepatic hilum.

PMID- 9915245
TI  - Concomitant major hepatectomy and inferior vena cava reconstruction.

PMID- 9915246
TI  - An alternative extraction site for laparoscopic donor nephrectomy.

PMID- 9915247
TI  - Genetic testings for cancer: the surgeon's critical role. Familial colon cancer.

PMID- 9915248
TI  - Genetic testings for cancer: the surgeon's critical role. Familial breast cancer.

PMID- 9915249
TI  - Genetic testings for cancer: the surgeon's critical role. Ethical and legal
      issues associated with genetic testing.

PMID- 9915250
TI  - Genetic testings for cancer: the surgeon's critical role. Clinical cancer
      genetics: 1998 (what's available to you in your practice).

PMID- 9915251
TI  - T cell-mediated xenograft rejection: specific tolerance is probably required for
      long term xenograft survival.
AB  - T cell-mediated mechanisms of xenograft rejection appear resistant to standard
      immunosuppression protocols used to prevent allograft rejection and,
      consequently, higher doses of immunosuppressive drugs are required to promote
      xenograft compared to allograft survival. Evidence from recent studies suggests
      that porcine xenografts may be especially immunogenic in humans because of a
      prominent and vigorous indirect xenoresponse and because of the ability of
      porcine endothelium to activate human T cells. This has led to an anxiety that
      systemic immunosuppressives, used as the mainstay of therapy for clinical
      xenotransplantation, may not allow the long-term survival of porcine organs
      transplanted into human recipients. This article will review the biology of T
      cell xenoresponses, present the case for the development of novel graft-specific
      immunosuppressive regimes in clinical xenotransplantation, and review recent
      experimental progress in this area.

PMID- 9915252
TI  - Chemical and lectin-gold electron microscopical studies of the expression of the
      Galalpha1-determinant in the pig aorta.
AB  - In the xenotransplantation research field, pig aortic endothelial cells are
      frequently used in different model systems, e.g., for the study of the
      xenoantibody-antigen reaction. The Gal(alpha1),3Gal determinant is the major
      target for human xenoreactive antibodies in pig tissue. Characterisation of the
      Gal(alpha1)- distribution in pig aortic endothelial cells is thus important for
      understanding the reaction occurring at the endothelial cells during the
      xenorejection. We have determined the complete structure of the major
      Gal(alpha1),3Gal terminated glycolipid, Gal(alpha1),3nLc4Cer. Structural studies
      were performed on isolated glycosphingolipids by mass spectrometry and NMR
      spectroscopy. The results show a predominance of the pentasaccharide among the
      Gal(alpha1)-terminated glycolipids but also the presence of several Gal(alpha1)
      terminated glycolipids with extended carbohydrate core chains. Ultrastructural
      localisation of the Galalpha1-antigen in pig aorta was done by lectin-gold
      electron microscopic studies of aortic wall sections using the Griffonia
      simplicifolia isolectin B4. Gal(alpha1)-determinants are predominantly localised
      on the luminal surface of pig aortic endothelial cells and endothelial cells of
      vasa vasorum and, to a lesser extent, vascular subendothelium.

PMID- 9915253
TI  - Complement activation in discordant hepatic xenotransplantation.
AB  - Little is known about hyperacute rejection in hepatic xenotransplantation.
      Information from clinical xenoperfusions suggests that the liver may be rejected
      by a mechanism less vigorous than either kidney or heart xenografts. We used the
      in vitro model of porcine hepatic sinusoidal endothelial cells (PHEC) incubated
      with either complement replete or deficient human serum to determine the relative
      roles of the classical and alternate pathways of complement in the immediate
      response to hepatic xenotransplantation. Our results suggest that either the
      classical or alternate pathways are capable of independently activating the
      complement cascade upon exposure to the porcine hepatic sinusoidal endothelium.
      Our results also imply that either pathway alone is capable of initiating similar
      degrees of injury as the entire cascade.

PMID- 9915254
TI  - Intravital microscopic investigation of xenogeneic microcirculation and impact of
      complement depletion by cobra venom factor.
AB  - Discordant xenografts are hyperacutely rejected within minutes. Disturbances in
      the microcirculation are considered to be the central mechanisms of hyperacute
      xenogeneic rejection (HXR). In this study intravital fluorescence microscopy was
      applied to investigate the dynamics of microcirculatory alterations in a setting
      in which HXR was inhibited by complement (C) depletion. Blood flow was measured
      as rat livers were perfused with isogeneic rat or xenogeneic human blood to
      assess the pattern of either physiological isogeneic hemoperfusion or in the
      course of HXR. Next, the complement system of the perfusate was inactivated by
      cobra venom factor (CVF) in order to inhibit HXR. Liver sinusoids of the
      isogeneic group were homogeneously perfused (sinusoidal perfusion rate 93.6+/
      0.3%), whereas in the xenogeneic group the sinusoidal perfusion rate dropped to
      67.1+/-3%. The perfusion in the periportal zone of an acinus was significantly
      lower ( 59.0+/-3.3%) than in the pericentral zone (76.2+/-3.1%). Treatment with
      CVF improved the sinusoidal perfusion to a value of 85.6+/-2.3%, physiological
      perfusion, however could not be reached. In contrast to the isogeneic group,
      massive white blood cell (WBC) and platelet accumulation was found in the
      xenogeneic group, especially in the terminal portal vessels and in the periportal
      zone of liver acini. WBC and platelet counts show that the adherence of these
      cells appears rapidly in the first 5 min after reperfusion as firm adherence. CVF
      was not able to inhibit WBC and platelet accumulation, indicating that WBC
      endothelial interactions do not require an intact complement system. Bile flow, a
      parameter of liver function, decreased only slightly during isogeneic perfusion.
      The addition of CVF to the rat blood reduced the bile flow to one half of the
      untreated isogeneic flow, indicating a hepatotoxic side-effect of CVF. In
      xenogeneic perfusion the bile flow dropped to 62.6% and with the addition of CVF
      to 37.5% in the first 15 min after reperfusion. The bile flow of the CVF treated
      groups recovered during the perfusion but could not reach isogeneic values.

PMID- 9915255
TI  - Pharmacologic immunosuppressive therapy and extracorporeal immunoadsorption in
      the suppression of anti-alphaGal antibody in the baboon.
AB  - The aim of this study was to deplete baboons of anti-(alpha)galactosyl (alphaGal]
      antibody and attempt to maintain depletion by pharmacologic immunosuppressive
      therapy (PI). In 12 experiments, involving nine baboons, repeated extracorporeal
      immunoadsorption (EIA) was carried out by plasma perfusion through immunoaffinity
      columns of synthetic alphaGal trisaccharide type 6. Five of the baboons were
      immunologically naive and four had undergone various procedures at least 6 months
      previously. All, however, had recovered lymphohematopoietic function and (with
      one exception) had levels of anti-alphaGal antibody within the normal range.
      Eleven protocols included continuous i.v. cyclosporine (to maintain whole blood
      levels of approximately 1,600 ng/ml). In addition, in ten protocols, the baboon
      received one or more of the following drugs: cyclophosphamide (1-20 mg/kg/day),
      mycophenolate mofetil (70-700 mg/ kg/day), brequinar sodium (1-12 mg/kg/day),
      prednisolone (1 mg/kg/day), melphalan (0.15-0.6 mg/kg/day), methylprednisolone
      (125 mg/day x3), and antilymphocyte globulin (ATG) (50 mg/kg/day x3). EIA was
      carried out on 1-9 occasions in each study and was temporarily successful in
      removing all antibody. When no PI was administered, antibody returned close to
      pre-EIA levels within 48 hr. Cyclosporine alone delayed the rate of antibody
      return only slightly. While EIA was continuing on a daily or alternate day
      schedule, antibody levels (both IgM and IgG) were maintained at 20-45% of pre-EIA
      levels. Once EIA was discontinued but PI maintained, IgM rose to 40-90% and IgG
      to 30-60% of pre-EIA levels. In vitro testing demonstrated significant
      cytotoxicity to pig cells at these antibody levels. We conclude that i) EIA
      utilizing columns of alphaGal trisaccharide is successful in temporarily
      depleting baboons of anti-alphaGal antibody, but ii) none of the PI regimens
      tested suppressed antibody production to levels which would be expected to
      prevent antibody-mediated rejection of pig xenografts. Additional strategies will
      therefore be required if xenotransplantation is to become a clinical reality.

PMID- 9915256
TI  - Antibodies to human adhesion molecules and von Willebrand factor: in vitro cross
      species reactivity in the xenotransplantation setting.
AB  - Endothelial cell activation is thought to play an important role in xenograft
      rejection through cell retraction and expression of pro-coagulant and pro
      inflammatory factors. Identification of antibodies recognizing porcine
      endothelial molecules would be useful to study and manipulate the inflammatory
      response to a xenograft. The aim of this study was to investigate the cross
      reactivity of antibodies directed against human adhesion molecules and von
      Willebrand factor (vWF). Binding of monoclonal antibodies (mAbs) directed against
      human CD3 1, CD44, CD49, CD54, CD62E, CD102, and CD106 was evaluated on resting
      and activated endothelial cells from human and pig by flow cytometry. Among 30
      antibodies tested, 4 were shown to react with pig cells. Two of them, directed
      against human CD62E (E-selectin) and rabbit CD106 (VCAM-1) reacted strongly with
      activated and/or resting pig cells, whereas two others, directed to human CD31
      (PECAM) and CD44 (H-CAM), bound weakly to pig cells. In addition, we analyzed the
      cross-reactivity of five polyclonal or monoclonal antibodies to human or pig vWF
      with human, baboon, rhesus, pig, and rat vWF. Binding of antibodies was tested by
      ELISA by using platelet lysates as source of vWF from the different species. Four
      anti-human or porcine vWF antibodies exhibited a broad reactivity with vWF from
      all species, whereas one anti-human vWF antibody was specific for primate vWF. In
      this study, we identified a small number of cross-reacting antibodies that may
      prove useful to study in vitro and in vivo xenogeneic responses. However, the
      weak antibody cross-reactivity observed with most porcine molecules points out
      the necessity of producing species-specific antibodies to study the immune
      response to xenografts or for use as specific immunosuppressive therapeutic
      reagents.

PMID- 9915257
TI  - Effects of ultraviolet B irradiation on fetal pig islet-like cell clusters.
AB  - Ultraviolet B (UV-B) irradiation of donor islets has previously been shown to
      result in the prolongation of their survival when transplanted into rodents. This
      study examined the in vitro and in vivo effects of UV-B irradiation on fetal pig
      islet-like cell clusters (ICCs), which like adult islets are being transplanted
      to reverse diabetes. Under control conditions, fetal pig ICCs were able to
      stimulate both human and pig peripheral blood mononuclear cells (PBMC) in mixed
      islet lymphocyte culture (MILC). Exposure of the ICCs to UV-B irradiation
      significantly reduced their ability to stimulate PBMC of both species in MILC
      when 600 J/m2 but not lower doses (300 and 400 J/m2) of irradiation were applied.
      In contrast, all doses of UV-B irradiation were effective in inhibiting the
      ability of pig and human PBMC to stimulate human PBMC in a mixed lymphocytes
      culture (MLC). This demonstrates that UV-B irradiation is effective in reducing
      xeno immunogenicity of pig antigens. A toxic effect of all doses of UV-B
      irradiation on ICCs was demonstrated in vitro with a reduction in 3H-thymidine
      incorporation of 57, 71, 64, and 80% at 150, 300, 450, and 600 J/m2,
      respectively. Toxicity of UV-B irradiation was also demonstrated when treated
      ICCs were transplanted beneath the renal capsule of SCID mice. The insulin
      content of the ICCs, 6 weeks after transplantation, was significantly reduced in
      the 600 J/m2 group (P<0.05). ICCs treated with UV-B irradiation (300 J/m2) in
      vitro and then transplanted beneath the renal capsule of BALB/c mice were
      rejected within 2 weeks as were untreated ICCs. Injection of cyclosporine (12.5
      mg/ kg/day) into these mice did not alter the results. It is concluded that UV-B
      irradiation is toxic to fetal pig ICCs and, in low dose, unable to prevent their
      rejection when transplanted into mice.

PMID- 9915258
TI  - Demonstration of multilineage chimerism in a nonhuman primate concordant
      xenograft model.
AB  - Prior studies from our laboratory have demonstrated that a nonmyeloablative
      conditioning regimen can induce transient mixed chimerism and renal allograft
      tolerance between MHC disparate cynomolgus monkeys. We have also shown that this
      preparative regimen can be extended to a concordant baboon to cynomolgus
      xenograft model by adding, to the post transplant protocol, therapy designed to
      prevent antibody production. Here we examine the use of brequinar (BQR) for this
      purpose and the efficacy of two new reagents developed to demonstrate the
      establishment of chimerism in the xenograft recipients. The cynomolgus recipients
      were conditioned with WBI (300 cGy), TI (700 cGy), ATG, cyclosporine, and
      brequinar sodium. To detect engraftment of the donor marrow, we prepared a
      polyclonal cynomolgus anti-baboon antibody (CABA) and a monoclonal antibody
      (215.1), which distinguish baboon and cynomolgus lymphocytes and granulocytes. We
      employed flow cytometry analysis to detect multilineage chimerism in the
      xenograft recipients. Five of the six recipients monitored using our new reagents
      (CABA and 215.1) developed detectable chimerism and only one of these animals
      lost its kidney to rejection. However, other complications have not permitted
      assessment of long-term outcome. The features of the multilineage chimerism
      included the detection of donor granulocytes (1.8-77.4%) and lymphocytes (2.4
      22.2%) for 9 to 37 days. Our new reagents permit the detection of multilineage
      mixed chimerism, which may be a predictor of xenograft tolerance. We also
      conclude that brequinar may be effective in preventing antibody formation, but
      because of its toxicity, it is probably not the drug of choice for extension of
      the mixed chimerism protocol to concordant xenografts.

PMID- 9915259
TI  - Literature update 1998, part 2.

PMID- 9915260
TI  - Bone loss in hypercalciuria: cause or consequence?

PMID- 9915261
TI  - Relationship of dialysis membrane and cause-specific mortality.
AB  - A number of studies have suggested that type of dialysis membrane is associated
      with differences in long-term outcome of patients undergoing hemodialysis, both
      in terms of morbidity and mortality. The purpose of this study was to determine
      the relationship of membrane type and specific causes of death. Data from the
      United States Renal Data System Case Mix Adequacy Study, a national random sample
      of hemodialysis patients who were alive on December 31, 1990, were used. Our
      study was limited to patients in this data set who were undergoing dialysis for
      at least 1 year (n = 4,055). For the main analytic models, membrane type was
      classified into two categories: unmodified cellulose or MC/SYN (which combines
      modified cellulose [MC] and synthetic membranes [SYN]). The relationships of
      membrane type and major causes of mortality were analyzed using Cox proportional
      hazards models, which adjusted for multiple (21) covariates, including
      demographics, comorbidity, Kt/V, and other parameters. Patients were censored at
      transplantation or 60 days after a switch to peritoneal dialysis. Compared with
      patients dialyzed with unmodified cellulose membranes, the adjusted relative
      mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from
      coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed
      with MC/SYN membranes. No statistically significant difference (all P > 0.1) was
      found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac
      causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82)
      between patients dialyzed with MC/SYN compared with unmodified cellulose
      membranes. These results offer support to reported experimental and observational
      clinical studies that have found that unmodified cellulose membranes may increase
      the risk for both infection and atherogenesis. Further studies are necessary to
      evaluate the possibility of confounding factors, compare more specific membrane
      types, and determine the pathophysiology linking membrane type to cause-specific
      mortality.

PMID- 9915262
TI  - Unique changes in interstitial extracellular matrix composition are associated
      with rejection and cyclosporine toxicity in human renal allograft biopsies.
AB  - Renal allograft loss from chronic rejection or cyclosporine toxicity (CsAT) is
      characterized by progressive interstitial fibrosis, yet the protein composition
      of these lesions is unknown. The normal tubular basement membrane (TBM) contains
      laminin (LM), collagen IV (containing collagen IV alpha chain 1 [COL4A1] and
      COL4A2), thrombospondin (TSP), and fibronectin (FN). Only TSP and FN extend
      beyond the TBM into the interstitial space. Very scanty amounts of interstitial
      collagens (I and III) are detected in the interstitium. In a pilot study of human
      renal allograft biopsy specimens, three patterns of extracellular matrix (ECM)
      composition were identified. Pattern 1 showed no change in ECM composition;
      pattern 2 showed generalized accumulation of collagens I and III in the
      interstitium; and pattern 3 showed new expression of COL4A3 and LM-beta2 in the
      proximal TBM. Criteria were established for the clinicopathological diagnosis of
      CsAT and rejection. These diagnoses were correlated with the ECM composition in
      22 renal allograft biopsy specimens. Control groups were examined in a similar
      manner and included native kidney biopsy specimens from patients with other
      allografts (n = 7), renal biopsy specimens from patients with glomerular disease
      (n = 9), and renal allograft biopsy specimens from patients without
      clinicopathological evidence of renal disease. These data show that rejection is
      associated with pattern 3 and CsAT is associated with pattern 2. Thus, detection
      of ECM composition may be a useful adjunct to standard microscopy in
      distinguishing rejection from CsAT in renal allograft biopsy specimens. These
      data suggest that interstitial fibrosis associated with rejection and CsAT result
      from different pathogenic mechanisms.

PMID- 9915263
TI  - Early immunologic and nonimmunologic predictors of arterial hypertension after
      renal transplantation.
AB  - We followed up a cohort of 680 renal transplant recipients receiving cyclosporine
      (CsA) immunosuppression with the aim of establishing an early-risk profile for
      early and late hypertension (HT) after renal transplantation (RTx), specifically
      comparing the predictive role of immunologic and nonimmunologic markers of graft
      prognosis. HT was defined as the need for antihypertensive drugs. The prevalence
      of HT was 65% at the time of RTx, increased to a peak of 78% at the end of the
      first year, and stabilized between 71% and 73% thereafter. Multivariate analysis
      identified HT at the time of RTx, basal renal disease, and grafting the right
      kidney as independent predictors of HT 3 months after RTx. The risk profile for
      HT 12 months after RTx included HT present at RTx, grafting the right kidney,
      markers of early ischemia-reperfusion injury (delayed graft function, cold and
      warm ischemia), and transplant from an elderly or female donor. Polytransfusion
      before RTx was associated with a decreased risk for HT, but retransplantation,
      increased reactivity against the lymphocyte panel, poor HLA compatibility, and
      early acute rejection did not portend an increased risk for the complication
      under study. The CsA schedule (dose, trough levels) correlated poorly with the
      blood pressure status of the patients, but simultaneous graft function was
      independently associated with late HT. In conclusion, the early predictive
      profile for HT after RTx includes, preferentially, nonimmunologic markers of
      graft prognosis. Hyperfiltration damage may be a significant pathogenic mechanism
      for this complication of RTx.

PMID- 9915264
TI  - Circadian rhythm of natriuresis is disturbed in nondipper type of essential
      hypertension.
AB  - We examined the circadian rhythm of urinary sodium excretion and the effects of
      sodium restriction on rhythm in both dipper and nondipper types of essential
      hypertension. Patients (n = 26) with essential hypertension were maintained on
      relatively high- (10 to 12 g/d of sodium chloride) and low-sodium (1 to 3 g/d)
      diets for 1 week each. On the last day of each diet, 24-hour blood pressures
      (BPs) were measured every 30 minutes noninvasively with an automatic device, and
      on the last 3 days, urinary samples were collected for both daytime (7:00 AM to
      9:30 PM) and nighttime (9:30 PM to 7:00 AM). Eight patients were classified as
      dippers based on a more than 10% reduction in mean arterial pressure (MAP) from
      daytime to nighttime on a high-sodium diet, and 18 patients were classified as
      nondippers. A nocturnal decrease in urinary sodium excretion rate (U(Na)V) on the
      high-sodium diet was observed in dippers (from 7.5 +/- 2.1 during the day to 5.3
      +/- 2.5 mmol/h at night; P < 0.0001), but not in nondippers (6.7 +/- 2.1 v 7.6 +/
      2.3 mmol/h; not significant). In nondippers, the night-day ratio of sodium
      excretion was significantly reduced from 1.2 +/- 0.4 to 0.8 +/- 0.3 (P < 0.003)
      by sodium restriction; at the same time, the night-day ratio of MAP was reduced
      from 0.98 +/- 0.04 to 0.93 +/- 0.05 (P < 0.05). In dippers, the night-day ratios
      of MAP and U(Na)V were not affected by sodium restriction, and both ratios
      remained constant at less than 1. Before sodium restriction, the night-day ratio
      of sodium excretion correlated with that of MAP (r = 0.78; P < 0.0001), whereas
      there was no significant correlation (r = -0.05) after sodium restriction. These
      findings showed that the circadian rhythm of renal sodium excretion differed
      between the two types of essential hypertension. The enhanced nocturnal
      natriuresis and diminished nocturnal BP fall on a high-sodium diet, recognized in
      nondippers, were both normalized by sodium restriction, resulting in circadian
      rhythms with nocturnal dips in U(Na)V and BP.

PMID- 9915265
TI  - Evaluating patients with renal failure for renal artery stenosis with gadolinium
      enhanced magnetic resonance angiography.
AB  - The incidence and prevalence of end-stage renal disease (ESRD) continues to
      increase, especially in the elderly population. The role of renovascular disease
      in contributing to ESRD is still not well defined. The objective of this study
      was to determine the utility of gadolinium (Gd)-enhanced magnetic resonance
      angiography (MRA) in evaluating elderly patients with renal insufficiency for
      renal artery stenosis (RAS). A 7-month prospective study conducted in a tertiary
      referral center evaluated 40 consecutive patients with progressive renal
      insufficiency (18 men and 22 women; mean age, 70 +/- 5.6 [standard deviation]
      years) and high clinical suspicion for renovascular disease with Gd-enhanced MRA.
      Digital subtraction angiography (DSA) was obtained in only those patients with
      significant RAS detected by MRA. Twelve patients had significant RAS. Six of
      these patients had percutaneous transluminal renal angioplasty (PTRA), five
      patients had renal artery bypass surgery, and one patient had a stent placed
      after PTRA. Seventy-eight renal arteries were satisfactorily evaluated by MRA.
      Twenty-two renal arteries were evaluated by both MRA and DSA. Of the 12
      significant stenoses detected by the MRA, 11 were confirmed by DSA and 1 was
      confirmed at the time of surgical revascularization. It is concluded that Gd
      enhanced MRA is a useful test for the evaluation of RAS in patients with
      compromised renal function.

PMID- 9915266
TI  - Abnormal renal vasodilation to an amino acid infusion in congestive heart
      failure: normalization by enalapril.
AB  - In congestive heart failure (CHF), the neurohormonal mechanisms that cause renal
      vasoconstriction, particularly those depending on the renin-angiotensin system,
      could interfere with renal vasodilating mechanisms. To elucidate this issue, we
      studied the kidney response to an amino acid infusion (known to cause renal
      vasodilation in healthy individuals) in eight patients with CHF. We found that
      the amino acid infusion (0.7 mL/kg/h of a 10% solution) elicited no renal
      hemodynamic response, in marked contrast to healthy subjects. We next
      hypothesized that the renin-angiotensin system (known to be activated in heart
      failure) has a role in the lack of response to the amino acid infusion. To test
      this hypothesis, we repeated the study after two 5-mg doses of enalapril, an
      inhibitor of the angiotensin-converting enzyme, administered 12 hours apart.
      After enalapril treatment, the amino acid infusion caused a 45% increase in mean
      renal blood flow (RBF) from 383 +/- 55 to 557 +/- 51 mL/min at the fifth hour (P
      < 0.05). This normalization of the renal response to the amino acid infusion
      occurred without changes in cardiac output or in systemic vascular resistance.
      Hence, the renal fraction of the cardiac output increased during the amino acid
      infusion. The recovery of the renal vascular response was not accompanied by an
      increase in glomerular filtration rate (GFR; filtration fraction decreased),
      suggesting a predominant efferent arteriole dilatation. Our study shows that, in
      heart failure, the kidney loses its ability to increase RBF in response to an
      amino acid load. This lack of renal vascular response can be restored by
      inhibiting the renin-angiotensin system and is unrelated to changes in systemic
      hemodynamics.

PMID- 9915267
TI  - Absence of hypoalbuminemia despite massive proteinuria in focal segmental
      glomerulosclerosis secondary to hyperfiltration.
AB  - We observed that some patients do not develop hypoalbuminemia despite the
      presence of massive proteinuria. To investigate whether the absence or presence
      of hypoalbuminemia could be a marker in the distinction between idiopathic focal
      segmental glomerulosclerosis (FSG) and FSG secondary to hyperfiltration, we
      reviewed all our patients with biopsy-proven FSG and persistent nephrotic-range
      proteinuria (>3.5 g/24 h). Patients who met these conditions were then separated
      into those with hypoalbuminemia (serum albumin level <3 g/dL; group I; n = 19)
      and those with normoalbuminemia (>3.5 g/24 h; group II; n = 18). All group I
      patients had nephrotic edema in contrast with the absence of edema in all group
      II patients. Serum cholesterol and triglyceride levels were significantly greater
      in group I. All group I patients had been diagnosed with idiopathic FSG. The
      diagnoses of group II patients were FSG secondary to massive obesity in eight
      patients (44%), vesicoureteral reflux in five patients (27%), and renal mass
      reduction in three patients (16%); only two patients (11%) in this group had
      idiopathic FSG. The case histories of 19 other patients with nephrotic-range
      proteinuria associated with hyperfiltering disorders (reflux nephropathy, massive
      obesity, renal mass reduction), but without renal biopsy, were also reviewed;
      despite massive proteinuria (5.8 +/- 3.1 g/24 h), serum albumin and total protein
      levels were always within normal values. In conclusion, patients with FSG
      secondary to hyperfiltration do not develop hypoalbuminemia or the other
      characteristic complications of nephrotic syndrome, despite the presence of
      massive proteinuria values.

PMID- 9915268
TI  - Neocytolysis contributes to the anemia of renal disease.
AB  - Neocytolysis is a recently described physiological process affecting the
      selective hemolysis of young red blood cells in circumstances of plethora.
      Erythropoietin (EPO) depression appears to initiate the process, providing the
      rationale to investigate its contributions to the anemia of renal disease. When
      EPO therapy was withheld, four of five stable hemodialysis patients showed
      chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red
      cell survival was short in the first 9 days, then normalized. Two of these four
      patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of
      pathological isotope enrichment of stool porphyrins when EPO therapy was held,
      again supporting selective hemolysis of newly released red cells that take up the
      isotope (one patient had chronic hemolysis indicated by isotope studies of blood
      and stool). Thus, neocytolysis can contribute to the anemia of renal disease and
      explain some unresolved issues about such anemia. One implication is the
      prediction that intravenous bolus EPO therapy is metabolically and economically
      inefficient compared with lower doses administered more frequently
      subcutaneously.

PMID- 9915269
TI  - Acute-phase response predicts erythropoietin resistance in hemodialysis and
      peritoneal dialysis patients.
AB  - We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to
      hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO
      resistance is usually attributed to iron or vitamin deficiency,
      hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute
      phase response, assessed by the level of the acute-phase C-reactive protein
      (CRP), correlates strongly with hypoalbuminemia and mortality in both
      hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional
      study of 92 HD and 36 PD patients, we examined the contribution of parathyroid
      hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters
      (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to
      EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and
      was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P
      < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct
      in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin
      levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded
      from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P =
      0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP
      level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were
      excluded from analysis in HD patients, low transferrin levels predicted high
      EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum
      levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and
      low transferrin levels, the pattern expected in the acute-phase response, not in
      iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase
      response was the most important predictor of EPO resistance.

PMID- 9915270
TI  - Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients
      with secondary hyperparathyroidism.
AB  - To evaluate the response of circulating intact parathyroid hormone (iPTH) on
      myocardial hypertrophy in hemodialysis (HD) patients with secondary
      hyperparathyroidism (SHPT), echocardiographic and neurohormonal assessments were
      performed over a 15-week period in 15 HD patients with SHPT before and after
      calcitriol treatment and 10 HD control patients with SHPT not receiving
      calcitriol therapy. We prospectively studied a group of 15 patients with
      significantly elevated iPTH levels (iPTH >450 pg/mL) receiving calcitriol (2
      microg after dialysis twice weekly). Clinical assessment, medication status, and
      biochemical and hematological measurements were performed once a month.
      Throughout the study, calcium carbonate levels were modified to maintain serum
      phosphate levels at less than 6 mg/dL, but body weight, antihypertensive
      medication, and ultrafiltration dose remained constant. In patients treated with
      calcitriol, an adequate reduction of iPTH levels was found (1,112 +/- 694 v 741
      +/- 644 pg/mL; P < 0.05) without changes in values of serum ionized calcium
      (iCa++), phosphate, or hematocrit. Blood pressure (BP), cardiac output (CO), and
      total peripheral resistance (TPR) did not significantly change. After 15 weeks of
      treatment with calcitriol, M-mode echocardiograms showed pronounced reductions in
      interventricular wall thickness (13.9 +/- 3.6 v 12.8 +/- 3.10 mm; P = 0.01), left
      ventricular posterior wall thickness (12.5 +/- 2.4 v 11.3 +/- 1.8 mm; P < 0.05),
      and left ventricle mass index (LVMi; 178 +/- 73 v 155 +/- 61 g/m2; P < 0.01).
      However, in control patients, these changes were not found after the treatment
      period. In addition, sequential measurements of neurohormonal mediator levels in
      patients receiving calcitriol showed that plasma renin (18.5 +/- 12.7 v 12.3 +/-
      11.0 pg/mL; P = 0.007), angiotensin II (AT II; 79.7 +/- 48.6 v 47.2 +/- 45.7
      pg/mL; P = 0.001), and atrial natriuretic peptide (ANP; 16.6 +/- 9.7 v 12.2 +/-
      4.4 pg/mL; P = 0.03) levels significantly decreased, whereas antidiuretic hormone
      (ADH), epinephrine, and norepinephrine levels did not change significantly. The
      percent change in LVMi associated with calcitriol therapy had a strong
      correlation with the percent change in iPTH (r = 0.52; P < 0.05) and AT II (r =
      0.47; P < 0.05) levels. We conclude that the partial correction of SHPT with
      intravenous calcitriol causes a regression in myocardial hypertrophy without
      biochemical or hemodynamic changes, such as heart rate, BP, and TPR. The changes
      in plasma levels of iPTH and, secondarily, plasma levels of neurohormones
      (especially AT II) after calcitriol therapy may have a key role in attenuating
      ventricular hypertrophy in SHPT.

PMID- 9915271
TI  - Calcium balance during pulse alfacalcidol therapy for secondary
      hyperparathyroidism in CAPD patients treated with 1.0 and 1.25 mmol/L dialysate
      calcium.
AB  - Hypercalcemia frequently occurs in continuous ambulatory peritoneal dialysis
      (CAPD) patients treated with calcium carbonate and vitamin D metabolites. To
      reduce the incidence of this complication, it has been proposed to use dialysate
      solutions with a low calcium concentration. However, there is concern that these
      solutions may lead to a negative calcium balance. We measured calcium balance in
      13 CAPD patients with secondary hyperparathyroidism who were treated with calcium
      carbonate and alfacalcidol, 2 microg twice weekly, while using 1.0- (1.0 group)
      and 1.25-mmol/L (1.25 group) dialysate calcium solutions. Calcium absorption was
      measured after the administration of Ca47. Results for the 1.0 (n = 6) and 1.25
      (n = 7) groups included fractional calcium absorptions of 0.14 (range, 0.09 to
      0.27) and 0.08 (range, 0.03 to 0.40; P = not significant [NS]) and calcium
      absorptions of 380 +/- 92 and 331 +/- 83 mg/d (P = NS). Dialysate calcium losses
      were 93 +/- 20 and 91 +/- 26 mg/d, and total calcium losses (dialysate and urine)
      were 106 +/- 16 and 108 +/- 40 mg/d (P = NS). Calcium balance was positive in all
      patients (274 +/- 92 and 223 +/- 65 mg/d; P = NS). These data suggest that the
      use of 1.0- and 1.25-mmol/L calcium solutions in conjunction with calcium
      carbonate and pulse alfacalcidol therapy is associated with a positive calcium
      balance in CAPD patients.

PMID- 9915272
TI  - Dialyzer-dependent changes in solute and water permeability with bleach
      reprocessing.
AB  - The effects of bleach reprocessing on the performance of high-flux dialyzers have
      not been comprehensively characterized. We compared the effects of automated
      bleach/formaldehyde reprocessing on solute and hydraulic permeability for
      cellulose triacetate (CT190) and polysulfone (F80B) dialyzers using an in vitro
      model. Dialyzers were studied after initial blood exposure (R0) and after 1 (R1),
      5 (R5), 10 (R10), and 15 (R15) reuse cycles. Ultrafiltration coefficient (K(uf)),
      serial clearances, and/or sieving coefficients (SCs) of urea, creatinine,
      vancomycin, inulin, myoglobin, and albumin were determined. Urea, creatinine, and
      vancomycin clearances and SCs did not significantly differ from R0 to R15 with
      either dialyzer. Inulin clearances and SC also did not significantly change from
      R0 to R15 for the CT190. However, these same values for the F80B significantly
      increased (P < 0.05). The inulin clearance and SC values for the CT190 dialyzer
      were significantly higher than those for the F80B at all stages except R15.
      Myoglobin clearances significantly increased over 15 reuses for both dialyzers (P
      < 0.01). However, CT190 myoglobin clearances were significantly higher at all
      stages (R0 = 37.7 +/- 9.7; R15 = 52.5 +/- 8.8 mL/min) than the F80B (R0 =
      negligible; R15 = 41.3 +/- 16.5 mL/min; P < 0.01). Albumin pre- and postdialysis
      SCs significantly increased for both dialyzers (P < 0.01). K(uf) for R0 and R15
      were 52.3 +/- 3.3 and 52.6 +/- 7.6 mL/h/mm Hg for CT190 (P = not significant) and
      48.8 +/- 4.4 and 87.3 +/- 7.0 mL/h/mm Hg for F80B (P < 0.0001). We conclude that
      bleach reprocessing significantly increases larger solute and hydraulic
      permeability of high-flux cellulosic and polysulfone dialyzers. This effect is
      more pronounced for the polysulfone membrane. Until 10 reuses or greater, the
      removal of solutes greater than 1,500 d is significantly compromised with the
      polysulfone dialyzer used in this study.

PMID- 9915273
TI  - Hemodialysis adequacy in Network 5: disparity between states and the role of
      center effects.
AB  - The purpose of this study was to determine whether an observed difference in
      hemodialysis adequacy between states in Network 5 was due to variations in
      patient characteristics and to what extent dialysis center effects played a role
      in the observed disparity between states. This was a retrospective observational
      study of 6,969 patients dialyzed at centers in Maryland and Virginia. There were
      3,919 patients on hemodialysis at 89 facilities in Virginia and 3,050 subjects
      dialyzed at 65 centers in Maryland. The mean urea reduction ratio (URR) was
      higher in Virginia compared with Maryland (68.2 +/- 0.1% v 66.0 +/- 0.2%, P <
      0.0001, respectively), and there continued to be a mean difference in URR of 1.8%
      between VA and MD (P < 0.0001) after adjusting for several covariates. The
      differences in URR between states varied depending on facility proprietary
      status, size as measured by number of stations, and relationship to hospital
      (free-standing or hospital-based). Furthermore, the center where a patient
      dialyzed, when treated as a fixed effect, accounted for 15% of the variance in
      URR. The mean difference of 1.8% in URR between states persisted in a mixed
      effects model that included all covariates along with adjusting for dialysis
      centers as a random effect. The disparity in dialysis adequacy between states in
      Network 5 could not be accounted for by demographic characteristics, case mix
      factors, or a large center effect observed in the region. Therefore, we conclude
      that underlying national reports on dialysis adequacy are heterogeneous results
      related to differences across regions such as states within a given Network. This
      difference between states is not explained by the strong center effect found on
      adequacy in this population of hemodialysis patients.

PMID- 9915274
TI  - Glycosaminoglycans prevent the functional and morphological peritoneal
      derangement in an experimental model of peritoneal fibrosis.
AB  - Chronic peritoneal dialysis results in fibrosis of the peritoneal membrane, which
      leads to progressive reduction in dialytic efficacy. It was recently shown that
      the intraperitoneal administration of glycosaminoglycans (GAGs) improves the
      efficiency of peritoneal dialysis in CAPD patients. To verify whether the
      favorable effects of GAGs are purely functional or involve a morphological
      amelioration of the peritoneal membrane structure, a study was carried out in an
      animal model of plasticizer-induced peritoneal fibrosis. Rats, in which chronic
      renal failure had been induced by subtotal nephrectomy, received either placebo,
      plasticizers (i.p.), or GAGs (s.c.), or plasticizers (i.p.) and GAGs (s.c.). Urea
      dialysate-to-plasma equilibrium, urea and albumin peritoneal clearance, and
      glucose reabsorption were determined. The peritoneal membrane was evaluated
      morphometrically and histologically. In plasticizer-treated animals, peritoneal
      function tests and morphology were dramatically deranged. On the contrary, the
      subcutaneous administration of GAGs in plasticizer-treated rats maintained the
      peritoneal physiology and normal structure. The subcutaneous administration of
      GAGs protects peritoneal functions by affecting the remodeling of the peritoneum,
      rather than by a purely functional or simple mechanical effect.

PMID- 9915275
TI  - Pharmacokinetics of intermittent intraperitoneal ceftazidime.
AB  - Ceftazidime is currently recommended as an alternative first-line agent in the
      treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of
      intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized.
      This study was designed to characterize the pharmacokinetic disposition of a
      single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours.
      This was a prospective, open label, pharmacokinetic study. The study was
      conducted in an independent, outpatient dialysis center. Ten volunteer continuous
      ambulatory peritoneal dialysis (CAPD) patients with and without residual renal
      function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for
      at least 2 months were recruited. Patients received a single dose of i.p.
      ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after
      an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour
      period. A high-pressure liquid chromatography (HPLC) assay was used to analyze
      ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of
      the 10 patients were non-anuric with a mean residual renal creatinine clearance
      of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the
      volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half
      life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No
      difference was detected between anuric and nonanuric patients. Mean plasma and
      dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7
      microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1
      microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime
      achieves serum and dialysate levels greater than the MIC of sensitive organisms
      over 48 hours.

PMID- 9915276
TI  - Peritoneoscopic versus surgical placement of peritoneal dialysis catheters: a
      prospective randomized study on outcome.
AB  - The most commonly used technique for insertion of peritoneal dialysis (PD)
      catheters is open surgical approach by minilaparotomy. Percutaneous implantation
      via the peritoneoscopic technique is expanding. Studies have suggested that PD
      catheters placed peritoneoscopically have longer survival rate than surgically
      placed ones. However, these studies were not randomized, where the surgical group
      had more patients who were obese or had prior abdominal surgery, and therefore,
      the selection of patients may have biased the results. We conducted a prospective
      randomized study in which patients underwent PD catheter placement by either the
      surgical or the peritoneoscopic technique. In the period from October 1992
      through October 1995, 148 double-cuff, curled-end, swan-neck PD catheters were
      placed in 148 patients. The outcome of the 76 patients in whom the PD catheters
      were placed peritoneoscopically was compared with that of the 72 patients in whom
      the catheters were placed surgically. Early peritonitis episodes (within 2 weeks
      of catheter placement) occurred in 9 of 72 patients (12.5%) in the surgical
      group, versus 2 of 76 patients (2.6%) in the peritoneoscopy group (P = 0.02).
      This higher rate of infection was most likely related to a higher exit site leak
      in the surgical group (11.1%) as compared with the peritoneoscopy group (1.3%).
      Moreover, peritoneoscopically placed catheters were found to have better survival
      (77.5% at 12 months, 63% at 24 months, and 51.3% at 36 months) than those placed
      surgically (62.5% at 12 months, 41.5% at 24 months, and 36% at 36 months) with P
      = 0.02, 0.01, and 0.04, respectively. We conclude that peritoneoscopically placed
      PD catheters have a longer survival rate than surgically placed ones.
      Furthermore, the rate of exit site leak and early infection is lower in the
      peritoneoscopic method.

PMID- 9915277
TI  - Collagenofibrotic glomerulopathy: a systemic disease.
AB  - Collagenofibrotic glomerulopathy is a recently discovered entity that is
      characterized by massive accumulation of spiraled and frayed collagen fibrils in
      mesangial and subendothelial areas, and elevated serum levels of procollagen III
      peptide. We report the autopsy of a patient who received continuous ambulatory
      peritoneal dialysis (CAPD) therapy for 7 years. Autopsy disclosed that massive
      accumulation of peculiar collagen fibers was found not only in the kidney, but
      also in many organs including spleen, liver, myocardium, and thyroid gland.
      Although the possibility remains that CAPD for 7 years might change or aggravate
      the deposition of abnormal collagen, the current case suggests a possibility that
      collagenofibrotic glomerulopathy is a systemic disorder with abnormal metabolism
      of type III collagen.

PMID- 9915278
TI  - Anti-glomerular basement membrane glomerulonephritis after extracorporeal shock
      wave lithotripsy.
AB  - Extracorporeal shock wave lithotripsy (ESWL) is a common noninvasive procedure
      for removal of upper urinary tract stones. We present a case of a man who
      developed anti-glomerular basement membrane (anti-GBM) disease after ESWL and
      review the two other cases described in the medical literature. In all cases, the
      affected individuals expressed the HLA DR2/HLA DR15 major histocompatibility
      antigen and developed a rapidly progressive anti-GBM-induced glomerulonephritis 3
      to 7 months after ESWL. Anti-GBM disease may be a rare complication of ESWL in
      susceptible individuals and should be considered in patients who develop acute
      renal failure after lithotripsy.

PMID- 9915279
TI  - Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic
      syndrome.
AB  - Immune thrombocytopenic purpura (ITP) mediated by quinine-dependent platelet
      reactive antibodies is well recognized. More recently there have been a number of
      reports of quinine-induced hemolytic-uremic syndrome (HUS). We describe a patient
      with quinine-induced immune thrombocytopenia who subsequently developed HUS after
      re-exposure to a single dose of this drug. To our knowledge, this is the first
      such case reported. Multiple quinine-dependent antibodies have been characterized
      in the patient's serum. Initially, quinine-dependent antibodies were directed
      solely against the platelet glycoprotein complex GPIb/IX. After rechallenge with
      quinine, there was broadening of quinine-dependent antibody specificities, which
      were now also directed against the platelet glycoprotein complexes GPIb/IX and
      GPIIb/IIIa, endothelial cells, and leukocytes. We have shown quinine-dependent
      antibody-mediated endothelial cell activation, which supports an immunopathogenic
      role for quinine-dependent antibodies in the causation of this disease.

PMID- 9915280
TI  - A puzzle solved.

PMID- 9915281
TI  - Neocytolysis: from outer space to the dialysis unit.

PMID- 9915282
TI  - Lessons from the Hemodialysis (HEMO) Study: an improved measure of the actual
      hemodialysis dose.
AB  - The Hemodialysis (HEMO) Study is a multicenter, prospective, randomized, 2 x 2
      factorial clinical trial designed to evaluate the efficacy of the dose of
      dialysis delivered ("standard" v "high") and dialysis membrane flux ("low" v
      "high") in reducing the morbidity and mortality of patients. The study is nearly
      half complete. Although both patients and investigators are blinded to the
      overall findings, which will not be available for another 3 years, important data
      have been generated from which a more accurate expression has been derived for
      the dose of dialysis received by each patient in the trial. This new expression
      of the effectiveness of dialysis, eKt/V, is a two-pool approximation derived from
      the traditional single-pool Kt/V (spKt/V) and time on dialysis. The dialysis
      prescription for the HEMO Study subjects is individualized to achieve the target
      dose for each patient and is closely monitored by measuring the more accurate and
      validated expression of eKt/N. Comparisons of the HEMO Study dose of dialysis
      with other studies have been confused by this unique expression (eKt/V) of the
      dialysis dose and adequacy adopted for the HEMO Study. The target eKt/V dose in
      the "standard" arm of the Study is 1.05 and in the "high" arm is 1.45 per
      dialysis thrice weekly. Based on data available from 426 subjects randomized to
      each arm, the target of 1.05 in the "standard" dose of the HEMO Study is
      equivalent to an spKt/V of 1.32, and that of the "high" dose, 1.67. Thus,
      volunteers in the "standard" arm of the Study are receiving a tightly controlled
      and closely monitored dose, which is above the current national mean spKt/V, and
      above that of the accepted minimum standard spKt/N of 1.2. When completed, the
      HEMO Study will show whether there are merits of a tightly controlled
      hemodialysis dose that is consistently delivered over a prolonged period and
      whether a high dose is beneficial and safe to prescribe.

PMID- 9915283
TI  - Current thinking on chronic renal allograft rejection: issues, concerns, and
      recommendations from a 1997 roundtable discussion.
AB  - Chronic rejection accounts for most renal allograft losses after the first year
      posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant
      surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to
      review critical issues surrounding chronic renal allograft rejection. This
      article summarizes the presentations and relevant discussions of this meeting
      regarding the cause of chronic rejection, clinical diagnoses, risk factors,
      future prospects for intervention strategies, and general recommendations for the
      transplant community. Growing evidence indicates that chronic rejection is the
      aggregate sum of irreversible immunologic and nonimmunologic injuries to the
      renal graft over time. A history of acute rejection episodes and inadequate
      immunosuppression, likely attributable to inconsistent cyclosporine exposure or
      poor patient compliance, are among the most recognizable immunologic risk factors
      for chronic rejection. Donor organ quality, delayed graft function, and other
      donor and recipient variables leading to reduced nephron mass are nonimmunologic
      factors that contribute to the progressive deterioration of renal graft function.
      Clinical management of renal transplant recipients should incorporate both
      immunologic- and nonimmunologic-based intervention strategies aimed at minimizing
      risk factors to thwart the progression of chronic rejection and improve long-term
      allograft and patient survival.

PMID- 9915284
TI  - The syndrome of inappropriate antidiuretic hormone secretion of unknown origin.

PMID- 9915285
TI  - Acute nonoliguric renal failure after renal transplantation.

PMID- 9915286
TI  - Protein-energy malnutrition in dialysis patients.

PMID- 9915287
TI  - Factors causing malnutrition in patients with chronic uremia.
AB  - There is abundant evidence that patients with chronic renal failure (CRF),
      including those treated by hemodialysis or peritoneal dialysis, have evidence of
      malnutrition with decreased body weight and subnormal values of serum proteins
      (suggesting a loss of visceral protein stores). Potential causes of an abnormal
      nutritional status that have been identified include an inadequate intake of
      protein or calories, an inability to activate the metabolic responses that are
      needed to achieve nitrogen and protein balance, or the presence of a disease that
      prevents activation of these metabolic responses or acts to stimulate the
      breakdown of body protein stores. Three critical metabolic responses to a limited
      protein intake have been identified: a reduction in the irreversible degradation
      of amino acids and the degradation of protein breakdown and an increase in
      protein synthesis in response to a meal. Metabolic acidosis blocks the first two
      responses and hence contributes to malnutrition in patients with chronic uremia.
      Other factors that could contribute to malnutrition include an inadequate intake
      because of anorexia or hormonal imbalances that impair protein turnover. In
      evaluating CRF patients with malnutrition, the first task is to ensure an
      adequate intake and to eliminate factors that impair the ability to achieve
      nitrogen balance.

PMID- 9915288
TI  - Therapeutic approaches to malnutrition in chronic dialysis patients: the
      different modalities of nutritional support.
AB  - Protein-energy malnutrition (PEM) is a common complication in maintenance
      hemodialysis and chronic peritoneal dialysis patients and is a powerful predictor
      of morbidity and mortality. Although this association does not prove that
      malnutrition is a cause of this increased morbidity and mortality, it is
      consistent with this possibility. There are a number of modalities of nutritional
      support for the prevention or treatment of PEM in maintenance dialysis patients.
      Routine methods include preventing PEM before the onset of maintenance dialysis
      therapy, dietary counseling, maintenance of an adequate dose of dialysis,
      avoidance of acidemia, and aggressive treatment of superimposed catabolic
      illness. Specific treatments of chronic dialysis patients who have persistently
      inadequate nutritional intake include food supplements, enteral tube feeding,
      intradialytic parenteral nutrition, and total parenteral nutrition. More
      experimental forms of nutritional therapy include dialytic nutrition (eg, using
      peritoneal dialysate or hemodialysate that contains amino acids), appetite
      stimulants (eg, megestrol acetate), or growth factors (eg, anabolic steroids,
      recombinant human growth hormone, or insulin-like growth factor-I).

PMID- 9915289
TI  - An evidence-based evaluation of intradialytic parenteral nutrition.
AB  - Malnutrition is a well-recognized comorbid condition in dialysis patients that
      contributes to the increased mortality seen in these patients. Multiple
      interventions have been tried in an effort to decrease mortality. The most
      controversial of these is intradialytic parenteral nutrition. In an era of high
      costs and shrinking budgets, it is important to critically examine published data
      to determine the quality of the data and to determine whether the reported
      results are valid and clinically applicable. Using an evidence-based approach,
      all published literature concerning intradialytic parenteral nutrition was
      reviewed, quality of the data determined, number needed to treat (NNT)
      calculated, and potential costs of treatment determined. Twenty-four studies that
      met the search criteria were identified. Only three studies were randomized; one
      of these was a feasibility study, and the other two were only of level B quality.
      The remaining studies were either case reports or observational studies of level
      C quality. The absolute risk reduction in mortality with intradialytic parenteral
      nutrition (IDPN) usage ranged from 0.12 to 0.65; relative risk reduction ranged
      from 0.48 to 0.74; NNT ranged from 2 to 17; cost ranged from $150,000,000 to
      $877,500,000; and 588 to 9,750 patients might be expected to experience a
      decrease in mortality. The results of this review indicate that the data
      supporting the use of IDPN are weak and a clear recommendation cannot be made.
      IDPN use in hemodialysis patients seems to be associated with decreased
      mortality. IDPN should be available for use in patients who meet previously
      published guidelines and who are not normoalbuminemic.

PMID- 9915290
TI  - Modality-specific nutrition support in ESRD: weighing the evidence.
AB  - Protein-calorie malnutrition affects a large fraction of patients with end-stage
      renal disease (ESRD) and contributes significantly to the high rates of mortality
      and morbidity observed in this population. Observational studies of specific
      interventions, including intradialytic parenteral nutrition (IDPN), suggest that
      aggressive nutrition support may be of some benefit to some patients with ESRD.
      Due in part to lack of data derived from prospective, randomized clinical trials,
      and to the large expense associated with these therapies, Medicare and other
      payers have strongly discouraged the prescription of IDPN and other intermittent,
      dialysis-specific methods of nutrition support, such as intraperitoneal nutrition
      (IPN). The "burden of proof" has been placed on the dialysis community. In
      response, we must continue to emphasize the importance of securing nutritional
      health for all patients on or anticipating renal replacement therapy.
      Intradialytic parenteral nutrition should be reserved for patients who are taking
      in sufficient calories yet are unable to tolerate oral or enteral protein-rich
      foods or formulas designed to meet daily protein requirements (> or = 1.5 g/kg in
      some patients). Intradialytic parenteral nutrition should not be prescribed in
      place of total parenteral nutrition (TPN) if the latter is truly needed. Creative
      methods of nutrition support, including the use of dietary supplements at
      dialysis (intradialytic oral or enteral nutrition), should be explored.
      Prospective clinical trials investigating the effects of nutrition support on
      survival, hospitalization rates, health-related quality of life, and functional
      status, are urgently needed.

PMID- 9915291
TI  - Nutritional status: a continuous quality improvement approach.
AB  - Intradialytic parenteral nutrition (IDPN) has been used as nutritional repletion
      in severely malnourished patients with end-stage renal disease (ESRD). This study
      presents a retrospective look at hemodialysis patients with malnutrition who were
      followed-up in the process of continuous quality improvement (CQI). The costs of
      intravenous supplies, hospitalizations, and morbidity are reviewed. The
      application of continuous quality improvement was used to identify and follow-up
      malnourished patients. There were significant decreases in number of
      hospitalizations and days in the hospital.

PMID- 9915292
TI  - Intraperitoneal nutrition.
AB  - Provision of nutrients through the peritoneum is as old as peritoneal dialysis
      (PD) itself. Studies with a shelf-stable amino acid-based dialysis solution have
      shown that the amino acids absorbed during one exchange quantitatively exceed the
      daily losses of proteins and amino acids. The supplementary amino acids are well
      tolerated and can induce protein anabolism in many malnourished PD patients, as
      is evident from increased nitrogen balance, insulin-like growth factor-1, and
      increased concentrations of serum proteins. Such solutions offer a convenient
      means of providing nutritional supplementation to address the major nutritional
      needs of PD patients.

PMID- 9915293
TI  - Pediatric experience with intradialytic parenteral nutrition and supplemental
      tube feeding.
AB  - Good nutrition is necessary to maximize the potential for growth and development
      in the pediatric age-group, but children, like adults with chronic renal failure
      and end-stage renal disease, may be anorectic and eat poorly. Infants and
      adolescents are at special risk because of the intense demands of growth during
      the first 2 years of life and again during puberty. Neurodevelopment is also
      adversely affected by poor nutrition, especially in infants. Approximately two
      thirds of pediatric dialysis patients are treated with chronic peritoneal
      dialysis, which results in significant protein losses in the dialysis effluent
      that can contribute to protein-calorie malnutrition. Meeting the nutritional
      needs of pediatric patients usually requires supplemental sources, such as
      intradialytic parenteral nutrition (IDPN) or tube feeding. Little is known about
      the effectiveness or desirability of IDPN in pediatric patients. More studies,
      especially of amino acid-based dialysis fluids for chronic peritoneal dialysis,
      need to be done before making IDPN a standard for pediatrics. Supplemental
      nasogastric or gastrostomy tube feedings have been very successful in maintaining
      and improving growth in infants, but no studies are available to evaluate their
      success in older children and adolescents. Recombinant growth hormone therapy, in
      addition to good nutrition and control of other growth factors such as acidosis,
      renal osteodystrophy, and chronic volume depletion, may be necessary for most
      growth-retarded children with chronic renal failure to achieve normal adult
      height.

PMID- 9915294
TI  - Technology assessment: relationship to coverage issues--a case for temporary
      coverage decisions.
AB  - Making appropriate coverage decisions has the potential of impacting patient
      outcomes. In both the public and private sectors, great diversity exists in the
      methodology and process used to make coverage decisions. Because definitional
      issues are important, they are described in this article. The underpinning of
      coverage decisions are a commitment to certain methodological principles,
      including embracing evidence-based medicine. The role of the federal government
      and local entities in regard to evidence production and process as well as
      methodology used to formulate policy decisions is complex and requires
      resolution. A temporary coverage decision can be a helpful tool when no consensus
      exists.

PMID- 9915295
TI  - Recommended criteria for initiating and discontinuing intradialytic parenteral
      nutrition therapy.
AB  - The indications for intradialytic parenteral nutrition (IDPN) in patients with
      end-stage renal disease remain controversial. Medicare has taken a position to
      severely limit the use of this form of nutritional therapy. Are there patients
      who do not meet the government criteria, yet would benefit from this therapy?
      Studies are required to answer this question, but they may be years away. In the
      interim, identification of appropriate patients, development of appropriate
      criteria for initiating and discontinuing therapy, as well as a proper
      reimbursement process should be considered for the treatment of severe
      malnutrition in this population of patients. This article discusses these topics
      and outlines a different approach to the use of IDPN.

PMID- 9915296
TI  - Proposed clinical trials in the evaluation of intradialytic parenteral nutrition.
AB  - New revised policies relating to intradialytic parenteral nutrition (IDPN)
      reimbursement by Medicare have made it difficult, if not impossible, to qualify
      malnourished hemodialysis patients for this potentially useful therapy. These
      policies were adopted by Medicare because of a lack of studies that provide clear
      documentation of the medical benefits of IDPN or their cost-effectiveness. We
      propose a limited study of the role of IDPN with and without anabolic growth
      factors to improve predefined nutritional parameters and document its cost
      effectiveness by monitoring hospitalization and mortality. The proposed study
      will be multicenter, prospective, limited to severely malnourished patients, and
      will include a control group that would receive standard of care.

PMID- 9915297
TI  - Experience and opinion of a dialysis patient regarding nutrition.

PMID- 9915298
TI  - Renocaval pressure gradient indicating left renal venous hypertension.

PMID- 9915299
TI  - Mitochondrial DNA variation in Koryaks and Itel'men: population replacement in
      the Okhotsk Sea-Bering Sea region during the Neolithic.
AB  - In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202
      individuals representing one Itel'men and three Koryak populations from different
      parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution
      restriction (RFLP) analysis and control region (CR) sequencing, and the resulting
      data were combined with those available for other Siberian and east Asian
      populations and subjected to statistical and phylogenetic analysis. Together, the
      Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D)
      of the four major haplotype groups (haplogroups) observed in Siberian and Native
      American populations (A-D). In addition, they exhibited mtDNAs belonging to
      haplogroups G, Y, and Z, which were formerly called "Other" mtDNAs. While
      Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were
      widely distributed in eastern Siberian and adjacent east Asian populations, the
      distribution of haplogroup Y was restricted within a relatively small area and
      pointed to the lower Amur River-Sakhalin Island region as its place of origin. In
      contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs
      remained unclear. Furthermore, phylogenetic and statistical analyses showed that
      Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east
      Asian populations than to those of the north Pacific Rim. These results were
      consistent with colonization events associated with the relatively recent
      immigration to Kamchatka of new tribes from the Siberian mainland region,
      although remnants of ancient Beringian populations were still evident in the
      Koryak and Itel'men gene pools.

PMID- 9915300
TI  - Percent of oxygen saturation of arterial hemoglobin among Bolivian Aymara at
      3,900-4,000 m.
AB  - A range of variation in percent of oxygen saturation of arterial hemoglobin
      (SaO2) among healthy individuals at a given high altitude indicates differences
      in physiological hypoxemia despite uniform ambient hypoxic stress. In populations
      native to the Tibetan plateau, a significant portion of the variance is
      attributable to additive genetic factors, and there is a major gene influencing
      SaO2. To determine whether there is genetic variance in other high-altitude
      populations, we designed a study to test the hypothesis that additive genetic
      factors contribute to phenotypic variation in SaO2 among Aymara natives of the
      Andean plateau, a population geographically distant from the Tibetan plateau and
      with a long, separate history of high-altitude residence. The average SaO2 of 381
      Aymara at 3,900-4,000 m was 92+/-0.15% (SEM) with a range of 84-99%. The average
      was 2.6% higher than the average SaO2 of a sample of Tibetans at 3,800-4,065 m
      measured with the same techniques. Quantitative genetic analyses of the Aymara
      sample detected no significant variance attributable to genetic factors. The
      presence of genetic variance in SaO2 in the Tibetan sample and its absence in the
      Aymara sample indicate there is potential for natural selection on this trait in
      the Tibetan but not the Aymara population.

PMID- 9915301
TI  - Estimating energy intake of urban women in Colombia: comparison of diet records
      and recalls.
AB  - As part of a larger study of energy-nutrition, we compared the performance of 24
      h diet recalls with estimated diet records kept by trained observers. The
      subjects were economically disadvantaged women (n = 85) in the city of Cali,
      Colombia. A 24 h recall and an estimated diet record were collected for each
      woman at 0 and approximately 3 and 6 months. Energy intake obtained from the
      estimated dietary records was validated against energy expenditure and used as
      the reference method. Energy and macronutrient intake were calculated from
      published food composition tables and proximate analyses of common foods. The
      number of food items consumed per woman per day, total and in each of 16 food
      groups, was tabulated. Energy and macronutrient intakes were 11-13% lower in the
      24 h recalls. The discrepancy energy could be largely accounted for by the lower
      number of food items in the recalls. The number of food items in eight of 16 food
      groups was significantly lower in the recalls compared to the records.
      Underreporting on the recalls was a general tendency in these subjects and not
      clearly related to average energy intake. We conclude that 24 h diet recalls
      underestimate energy and nutrient intake in this population and are not suitable
      for studies of human energetics.

PMID- 9915302
TI  - Historical biogeography of tamarins, genus Saguinus: the molecular phylogenetic
      evidence.
AB  - Hypotheses of the historical biogeography of tamarins (genus Saguinus) based on
      variation in coat colors and body size are tested using phylogenetic
      relationships inferred from mitochondrial DNA (mtDNA) sequence data. Samples from
      all 12 species of Saguinus and several subspecies are included in the analysis.
      Approximately 1,200 bases of mtDNA sequence from the cytochrome b and D-loop
      regions are reported for the tamarins and several outgroup taxa. Parsimony
      analysis of the mtDNA sequence data reveals Saguinus to be a monophyletic taxon
      composed of two major clades: one, the Small-bodied clade, contains S.
      nigricollis, S. tripartitus, and S. fuscicollis, and the other, the Large-bodied
      clade, contains the other nine species. The phylogenetic relationships among
      tamarins inferred from the mtDNA sequence data reject previous hypotheses for the
      historical biogeography of tamarins and suggest different dispersal routes for
      this group of New World monkeys. The molecular data suggest that tamarins
      dispersed across South America in two major waves from an origin somewhere south
      of the Amazon. One wave moved in a westerly direction, whereas the other moved in
      a northeastern direction toward the Amazon delta and then west along the northern
      portion of the continent into northern Colombia and Panama.

PMID- 9915303
TI  - The form of the supraorbital margin as a criterion in identification of sex from
      the skull: investigations based on modern human skulls.
AB  - Sexual dimorphism in the shape of the supraorbital margin was reported by Broca
      and various subsequent authors, but no consistently applied, precise definition
      has been established. In this study of modern human skulls, the value of our
      definition of the sex-related difference in this area in the identification of
      sex from the skull was investigated. It was found that this feature can be
      assessed reliably, is strongly related to sex, and is independent of the side.
      The accuracy of identification of sex using this method alone was found to be
      about 70%.

PMID- 9915304
TI  - Sexual dimorphism in the face of Australopithecus africanus.
AB  - Recently discovered crania of Australopithecus africanus from Sterkfontein Member
      4 and Makapansgat enlarge the size range of the species and encourage a
      reappraisal of both the degree and pattern of sexual dimorphism. Resampling
      methodology (bootstrapping) is used here to establish that A. africanus has a
      greater craniofacial size range than chimpanzees or modern humans, a range which
      is best attributed to a moderately high degree of sexual dimorphism. Compared to
      other fossil hominins, this variation is similar to that of Homo habilis (sensu
      lato) but less than that of A. boisei. The finding of moderately high dimorphism
      is corroborated by a CV-based estimate and ratios between those specimens
      considered to be male and those considered to be female. Inferences about the
      pattern of craniofacial dimorphism in the A. africanus face currently rely on the
      relationship of morphology and size. Larger specimens, particularly Stw 505, show
      prominent superciliary eminences and glabellar regions, but in features related
      in part to canine size, such as the curvature of the infraorbital surface, large
      and small specimens of A. africanus are similar. In this respect, the pattern
      resembles that of modern humans more so than chimpanzees or lowland gorillas. A.
      africanus may also show novel patterns of sexual dimorphism when compared to
      extant hominines, such as in the form of the anterior pillar. However, males of
      the species do not exhibit characteristics of more derived hominins, such as A.
      robustus.

PMID- 9915305
TI  - Double-edged swords: volatile anesthetics both enhance and inhibit ligand-gated
      ion channels.

PMID- 9915306
TI  - Goals- and values-directed approach to informed consent in the "DNR" patient
      presenting for surgery: more demanding of the anesthesiologist?

PMID- 9915307
TI  - Population pharmacokinetics of piritramide in surgical patients.
AB  - BACKGROUND: Piritramide is a synthetic opioid used for postoperative analgesia in
      several European countries. The authors present a mixed-effects model of its
      population pharmacokinetics in patients undergoing surgery. METHODS: After
      institutional approval and informed patient consent was obtained, 29 patients who
      were classified as American Society of Anesthesiologists physical status I or II
      and aged 21-82 yr were enrolled in the study. They received 0.2 mg/kg piritramide
      as an intravenous bolus before anesthesia was induced. Central venous blood
      samples were drawn for as long as 48 h after administration of the drug. The
      plasma concentration of piritramide was determined by gas chromatography. The
      concentration-time data were analyzed by mixed-effects modeling. Target
      controlled infusions and intermittent bolus regimens were simulated to identify a
      regimen suitable for patient-controlled analgesia based on population
      pharmacokinetics and published pharmacodynamic data. RESULTS: The
      pharmacokinetics of piritramide were described adequately by a linear three
      compartment model. Patient age and weight were significant covariates. The values
      of the pharmacokinetic parameters are: V1 = 50.5 [1], V2 = 150 x (1 + 9.32 x 10(
      3) x (age - 47 yr)) [l], V3 = 212 x (1 + 6.37 x 10(-3) x (age - 47 yr)) [l], Cl1
      = 0.56 x (1 - 6.14 x 10(-3) x (age - 47 yr)) [l/min], Cl2 = 8.25 x (1 + 2.02 x
      10(-2) x (Wt - 74 kg)) [l/min], Cl3 = 0.80 [l/min]. The age of 47 yr and the
      weight of 74 kg refer to the median values for these factors in the patients
      studied. Rapid distribution, slow distribution, and elimination half-lives for
      the median patient are 0.05, 1.34, and 10.43 h, respectively. The context
      sensitive half-time after a 24-h infusion is predicted at 10.5 h in a 75-yr-old
      patient compared with 7 h for the median patient. CONCLUSIONS: Piritramide is
      distributed extensively and eliminated slowly. The pharmacokinetic profile of the
      drug allows for intermittent bolus administration even when constant effect
      compartment concentrations are desirable, e.g., for PLA.

PMID- 9915308
TI  - A pharmacodynamic explanation for the rapid onset/offset of rapacuronium bromide.
AB  - BACKGROUND: Nondepolarizing muscle relaxants differ in their time course at the
      laryngeal adductors and the adductor pollicis, a result of differences in
      equilibration delays between plasma and effect sites, the sensitivity of each
      muscle to the relaxant, and the steepness of the concentration-effect relation at
      each muscle (the Hill factor). To determine whether similar differences exist for
      rapacuronium, a muscle relaxant with rapid onset and offset, the authors
      determined its pharmacodynamic characteristics. METHODS: The twitch tensions of
      the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff
      positioned at the vocal cords) were measured in 10 volunteers who were
      anesthetized with propofoL Rapacuronium, 1.5 mg/kg, was given and blood samples
      were collected. A semiparametric effect compartment pharmacodynamic model was fit
      to values for rapacuronium plasma concentrations and twitch tension of the
      adductor pollicis and laryngeal adductors. RESULTS: Equilibration between the
      rapacuronium plasma concentration and both effect sites was rapid (typical values
      for the rate constant for equilibration between plasma and the effect site are
      0.405 per min for the adductor pollicis and 0.630 per min for the laryngeal
      adductors) and was more rapid at the laryngeal adductors than at the adductor
      pollicis (ratio, 1.59+/-0.16; mean +/- SD). The steady state rapacuronium plasma
      concentration that depressed twitch tension by 50% and the Hill factor were
      similar for the two muscles. CONCLUSIONS: The rapid onset and offset of
      rapacuronium can be explained by the rapid equilibration between concentrations
      in plasma and at the effect site. Unlike the finding for other nondepolarizing
      muscle relaxants, the laryngeal muscles are not resistant to rapacuronium.

PMID- 9915309
TI  - Influence of renal failure on the pharmacokinetics and neuromuscular effects of a
      single dose of rapacuronium bromide.
AB  - BACKGROUND: Because renal function affects the elimination of muscle relaxants,
      each new muscle relaxant must be evaluated in patients with renal failure.
      Accordingly, the neuromuscular effects and pharmacokinetics of rapacuronium were
      identified in patients with renal failure. METHODS: Rapacuronium (1.5 mg/kg) was
      administered to 10 healthy volunteers and 10 patients with renal failure who were
      undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with
      propofol. The adductor pollicis muscle twitch tension was monitored. Plasma
      samples were obtained frequently for a period of 8 h to measure the
      concentrations of ORG9487 and its metabolite, ORG9488. Pharmacokinetic parameters
      were determined using mixed-effects modeling. RESULTS: One patient was excluded
      from analysis because he was taking phenytoin chronically. Twitch depression at 1
      min was less in patients than in healthy volunteers (median values: 92% in
      patients, 99% in volunteers). The times to 90% and peak twitch depression; to
      10%, 25%, and 75% twitch recovery; and to 70% and 80% train-of-four ratios were
      similar in volunteers and patients. Rapacuronium's clearance was 32% less in
      patients with renal failure; in both groups, clearance decreased 0.909% per year
      of age compared with the value in a 30 yr old. The steady state distribution
      volume was 14% less in women than in men and 16% less in patients than in
      volunteers. For ORG9488, clearance was 85% less in patients than in volunteers.
      CONCLUSIONS: The neuromuscular effects of a single dose of rapacuronium are
      affected minimally by renal failure. However, the decreased clearance of
      rapacuronium and its potent metabolite in renal failure suggests that repeated
      dosing of rapacuronium may lead to prolonged effects in patients with renal
      failure.

PMID- 9915310
TI  - The use of propofol, nitrous oxide, or isoflurane does not affect the
      reproductive success rate following gamete intrafallopian transfer (GIFT): a
      multicenter pilot trial/survey.
AB  - BACKGROUND: Whether anesthetic agents administered during gamete intrafallopian
      transfer (GIFT) affect reproductive outcome is controversial. This multicenter
      pilot trial and survey had two purposes: to evaluate the effect of propofol,
      nitrous oxide, midazolam, and isoflurane on pregnancy outcome after GIFT, and to
      determine if a larger prospective, randomized study is warranted. METHODS: A
      written invitation was mailed to all 50 fertility programs in the United States
      that are members of the Society for Assisted Reproductive Technology and perform
      more than 30 GIFT procedures per year. They were invited to contribute
      information from the medical records of women who underwent GIFT during the
      calendar years 1993 and 1994. They were asked to document whether propofol,
      nitrous oxide, midazolam, a potent inhaled anesthetic agent was used during the
      GIFT procedure; if the woman became pregnant; and if she delivered at least one
      live neonate. RESULTS: Seven medical centers participated and contributed data
      from 455 women. The clinical pregnancy rate (number of pregnancies/total number
      of GIFT procedures) and the delivery rate (number of women who delivered at least
      one live baby/total number of GIFT procedures) were 35% and 32%, respectively. A
      statistically significant difference could not be found in the clinical pregnancy
      or delivery rates between those women who received propofol, nitrous oxide,
      midazolam, or isoflurane during GIFT and those who did not. CONCLUSIONS: No agent
      related differences in pregnancy rates were found when propofol, nitrous oxide,
      isoflurane, or midazolam was used as part of the anesthetic technique for GIFT.
      Therefore, a more extensive prospective trial does not appear to be warranted.

PMID- 9915311
TI  - Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.
AB  - BACKGROUND: Patients with cirrhosis have a reduced life expectancy. Anesthesia
      and surgery have been associated with clinical decompensation in patients with
      cirrhosis. METHODS: The authors retrospectively reviewed the records of all
      patients with the diagnosis of cirrhosis who underwent any surgical procedure
      under anesthesia at their institution between January 1980 and January 1991 (n =
      733). Univariate and multivariate analyses were used to identify the variables
      associated with perioperative complications and short- and long-term survival.
      RESULTS: The perioperative mortality rate (within 30 days of surgery) was 11.6%.
      The perioperative complication rate was 30.1%. Postoperative pneumonia was the
      most frequent complication. Multivariate factors that were associated with
      perioperative complications and mortality included male gender, a high Child-Pugh
      score, the presence of ascites, a diagnosis of cirrhosis other than primary
      biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine
      concentration, the diagnosis of chronic obstructive pulmonary disease,
      preoperative infection, preoperative upper gastrointestinal bleeding, a high
      American Society of Anesthesiologists physical status rating, a high surgical
      severity score, surgery on the respiratory system, and the presence of
      intraoperative hypotension. CONCLUSION: Risk factors have been identified for
      patients with cirrhosis who undergo anesthesia and surgery.

PMID- 9915312
TI  - Ulnar neuropathy in surgical patients.
AB  - BACKGROUND: The goal of this project was to study the frequency and natural
      history of perioperative ulnar neuropathy. METHODS: A prospective evaluation of
      ulnar neuropathy in 1,502 adult patients undergoing noncardiac surgical
      procedures was performed. Patients were assessed with a standard questionnaire
      and neurologic examination before surgery, daily during hospitalization in the
      first week after surgery, and by telephone if they were discharged before 1
      postoperative week. Patients in whom ulnar neuropathy developed were followed for
      2 yr. RESULTS: Ulnar neuropathy developed in seven patients (0.5%; 95% confidence
      interval, 0.2% to 1.0%). Six of the seven patients were men. Symptoms of ulnar
      neuropathy began 2-7 days after surgery. Manifestations were mild and confined to
      sensory deficits in six patients. Symptoms resolved in four patients within 6
      weeks. The remaining three patients had residual symptoms 2 yr later.
      CONCLUSIONS: In this surgical population, ulnar neuropathy was an infrequent
      complication. It occurred primarily in men who were 50-75 yr old and was not
      symptomatic until several days after surgery. Gender-dependent differences in the
      anatomy of the ulnar nerve and related structures at the elbow may serve as risk
      factors for ulnar neuropathy in patients having surgery.

PMID- 9915313
TI  - Sevoflurane has no effect on sinoatrial node function or on normal
      atrioventricular and accessory pathway conduction in Wolff-Parkinson-White
      syndrome during alfentanil/midazolam anesthesia.
AB  - BACKGROUND: The effects of sevoflurane on the electrophysiologic properties of
      the human heart are unknown. This study evaluated the effects of sevoflurane on
      the electrophysiologic properties of the normal atrioventricular conduction
      system, and on the accessory pathways in patients with Wolff-Parkinson-White
      syndrome, to determine its suitability as an anesthetic agent for patients
      undergoing ablative procedures. METHODS: Fifteen patients with Wolff-Parkinson
      White syndrome undergoing elective radiofrequency catheter ablation were studied.
      Anesthesia was induced with alfentanil (20-50 microg/kg) and midazolam (0.15
      mg/kg), and vecuronium (20 mg) and maintained with alfentanil (0.5 to 2 microg x
      kg(-1) x min(-1)) and midazolam (1 or 2 mg every 10-15 min, as required). An
      electrophysiologic study measured the effective refractory period of the right
      atrium, atrioventricular node, and accessory pathway; the shortest conducted
      cycle length of the atrioventricular node and accessory pathway during atrial
      pacing; the effective refractory period of the right ventricle and accessory
      pathway; and the shortest retrograde conducted cycle length of the accessory
      pathway during ventricular pacing. Parameters of sinoatrial node function
      included sinus node recovery time, corrected sinus node recovery time, and
      sinoatrial conduction time. Intraatrial conduction time and the atrial-His
      interval were also measured. Characteristics of induced reciprocating
      tachycardia, including cycle length, atrial-His, His-ventricular, and
      ventriculoatrial intervals, also were measured. Sevoflurane was administered to
      achieve an end-tidal concentration of 2% (1 minimum alveolar concentration), and
      the study measurements were repeated. RESULTS: Sevoflurane had no effect on the
      electrophysiologic parameters of conduction in the normal atrioventricular
      conduction system or accessory pathway, or during reciprocating tachycardia.
      However, sevoflurane caused a statistically significant reduction in the
      sinoatrial conduction time and atrial-His interval but these changes were not
      clinically important. All accessory pathways were successfully identified and
      ablated. CONCLUSIONS: Sevoflurane had no effect on the electrophysiologic nature
      of the normal atrioventricular or accessory pathway and no clinically important
      effect on sinoatrial node activity. It is therefore a suitable anesthetic agent
      for patients undergoing ablative procedures.

PMID- 9915314
TI  - Perioperative pulmonary aspiration in infants and children.
AB  - BACKGROUND: Pulmonary aspiration of gastric contents during the perioperative
      period in infants and children may be associated with postoperative mortality or
      pulmonary morbidity. There has not been a recent determination of the frequency
      of this event and its outcomes in infants and children. METHODS: The authors
      prospectively identified all cases of pulmonary aspiration of gastric contents
      during the perioperative courses of 56,138 consecutive patients younger than 18
      yr of age who underwent 63,180 general anesthetics for procedures performed in
      all surgical specialties from July 1985 through June 1997 at the Mayo Clinic.
      RESULTS: Pulmonary aspiration occurred in 24 patients (1: 2,632 anesthetics;
      0.04%). Children undergoing emergency procedures had a greater frequency of
      pulmonary aspiration compared to those undergoing elective procedures (1:373 vs.
      1:4,544, P < 0.001). Fifteen of the 24 children who aspirated gastric contents
      did not develop respiratory symptoms within 2 h of aspiration, and none of these
      15 developed pulmonary sequelae. Five of these nine children who aspirated and in
      whom respiratory symptoms developed within 2 h subsequently had pulmonary
      complications treated with respiratory support (P < 0.003). Three children were
      treated with mechanical ventilation for more than 48 h, but no child died of
      sequelae of pulmonary aspiration. CONCLUSIONS: In this study population, the
      frequency of perioperative pulmonary aspiration in children was quite low.
      Serious respiratory morbidity was rare, and there were no associated deaths.
      Infants and children with clinically apparent pulmonary aspiration in whom
      symptoms did not develop within 2 h did not have respiratory sequelae.

PMID- 9915315
TI  - Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute
      phase response after cardiopulmonary bypass (CPB).
AB  - BACKGROUND: Compromised splanchnic perfusion and the resulting intestinal mucosal
      injury leads to a decreased mucosal barrier function, which allows translocation
      of intestinal flora and endotoxemia. The authors evaluated the effects of
      milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent
      acute-phase response in patients undergoing coronary artery bypass grafting.
      METHODS: This open, placebo-controlled randomized clinical study enrolled 22
      adult patients in two groups. Before induction of anesthesia, baseline values
      were obtained and patients were randomized to receive milrinone (30 microg/kg
      bolus administered progressively in 10 min, followed by a continuous infusion of
      0.5 microg x kg(-1) x min(-1)) or saline. The following parameters were
      determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed
      venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and
      hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid
      A, and C-reactive protein. RESULTS: Milrinone did not prevent gastrointestinal
      acidosis as measured by pHi, but its perioperative administration resulted in
      significantly higher pHi levels compared with control. Venous and hepatic venous
      endotoxin and the interleukin 6 concentration were reduced significantly in the
      milrinone group. Serum amyloid A values were attenuated in the milrinone group 24
      h after surgery. No significant differences could be seen in routinely measured
      oxygen transport-derived variables. CONCLUSIONS: Perioperative administration of
      low-dose milrinone may have antiinflammatory properties and may improve
      splanchnic perfusion in otherwise healthy patients undergoing routine coronary
      artery bypass grafting.

PMID- 9915316
TI  - Volume kinetics of Ringer's solution in hypovolemic volunteers.
AB  - BACKGROUND: The amount of Ringer's solution needed to restore normal blood
      volumes is thought to be three to five times the volume of blood lost. This
      therapy can be optimized by using a kinetic model that takes accounts for the
      rates of distribution and elimination of the infused fluid. METHODS: The authors
      infused 25 ml/kg Ringer's acetate solution into 10 male volunteers who were 23 to
      33 yr old (mean, 28 yr) when they were normovolemic and after 450 ml and 900 ml
      blood had been withdrawn. One-volume and two-volume kinetic models were fitted to
      the dilution of the total venous hemoglobin and plasma albumin concentrations.
      RESULTS: Withdrawal of blood resulted in a progressive upward shift of the
      dilution-time curves of both markers. The two-volume model was statistically
      justified in 56 of the 60 analyzed data sets. The hemoglobin changes indicated
      that the body fluid space expanded by the infused fluid had a mean total volume
      of 10.7 l(+/-0.9 SEM). The elimination rate constant (kr) decreased with the
      degree of hypovolemia and was 133 ml/min (22 ml/min [SEM]), 100 ml/min (39 ml/min
      [SEM]), and 34 ml/min (7 ml/min [SEM]), respectively (P < 0.01). Plasma albumin
      indicated a slightly larger body fluid space expanded by the infused fluid, but
      kr was less (P < 0.02). Hypovolemia reduced the systolic and diastolic blood
      pressures by approximately 10 mmHg (P < 0.05). CONCLUSIONS: The dilution of the
      blood and the retention of infused Ringer's solution in the body increases in the
      presence of hypovolemia, which can be attributed chiefly to a reduction of the
      elimination rate constant.

PMID- 9915317
TI  - Targeting effect compartment or central compartment concentration of propofol:
      what predicts loss of consciousness?
AB  - BACKGROUND: An effect compartment has been postulated, and the ke0 has been
      quantified for several intravenous anesthetic drugs using electroencephalography
      (EEG) as the measure of effect. The authors wanted to validate that loss of
      responsiveness (LOR) was related to targeting an effect compartment concentration
      rather than a central compartment (plasma) concentration. METHODS: Twenty
      American Society of Anesthesiologists physical status I and II patients were
      randomized to receive propofol administered to a target central compartment or
      target effect compartment site concentration of 5.4 microg/ml propofol
      administered by a target-controlled infusion (TCI) using a previously validated
      set of pharmacokinetic parameters and a ke0 of 0.63 min(-1). Every 30 s for the
      first 5 min and every minute for the second 5 min the patients were asked to open
      their eyes. The time to LOR was measured by a blinded investigator. The authors
      also simulated the time to reach the desired target effect site concentration
      using varying ke0 values. RESULTS: The median time to LOR in the group targeted
      to a predicted plasma propofol concentration was 3.02 min and 1.23 min in the
      group targeted to a predicted effect compartment propofol concentration (P <
      0.05). LOR to command in both groups occurred at a predicted median effect
      compartment concentration of 4.55 microg/ml. Simulations demonstrated that the
      time predicted to LOR targeting an effect site concentration of 5.4 microg/ml is
      markedly altered by the value chosen for the ke0. CONCLUSIONS: This study
      confirms the utility of the ke0 value to describe the effect compartment for
      propofol. The authors also illustrate the importance of selecting the correct ke0
      value for the pharmacokinetic parameters used within the TCI system.

PMID- 9915318
TI  - Equivalent analgesia and side effects during epidural and pharmacokinetically
      tailored intravenous infusion with matching plasma alfentanil concentration.
AB  - BACKGROUND: Recently, several clinical studies comparing intravenous and epidural
      infusions of fentanyl and its derivatives suggested that epidural infusions act
      primarily by systemic absorption to produce supraspinal analgesia. To evaluate
      this hypothesis, the authors used pharmacokinetically tailored intravenous
      infusions to produce matching plasma alfentanil concentrations during epidural
      and intravenous administration. The analgesia and side effects achieved with each
      mode of administration were compared. METHODS: Twelve volunteers participated in
      this placebo-controlled crossover study. The pain model was cutaneous electric
      stimulation of the finger and toe. The test battery included subjective rating of
      pain intensity; end-tidal carbon dioxide level; pupil size; ratings of alertness,
      nausea, and pruritus; and a plasma alfentanil assay. On one test day, the
      participants received epidural alfentanil (400 microg bolus + a 400-microg/h
      infusion for 2 h) and an intravenous saline infusion. The test battery was
      administered at regular intervals. On another test day, the participants received
      epidural saline and a computer-controlled intravenous infusion of alfentanil. The
      testing protocol was repeated as on the first test day. On the day the placebo
      was administered, the participants received epidural and intravenous saline
      infusions. The order of the placebo day was randomized. RESULTS: Plasma
      alfentanil concentration-time profiles were identical during epidural and
      intravenous infusions. A nearly equivalent analgesic response was observed with
      epidural and intravenous alfentanil at the upper and lower extremities. There
      were no differences in side effects for epidural and intravenous administration.
      CONCLUSIONS: The systemic redistribution of alfentanil accounts for most of the
      analgesia and effects produced by epidural infusion.

PMID- 9915319
TI  - Rocuronium-induced neuromuscular block is affected by chronic carbamazepine
      therapy.
AB  - BACKGROUND: Patients on chronic anticonvulsant drugs are relatively resistant to
      certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium,
      pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and
      atracurium. This study investigated the influence of chronic carbamazepine
      therapy on the neuromuscular block induced by the new muscle relaxant rocuronium.
      METHODS: Twenty-two otherwise healthy individuals scheduled for neurosurgical
      operations were studied: 11 of them were on chronic treatment with carbamazepine;
      the others served as control subjects. The median duration of carbamazepine
      therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam,
      anesthesia was induced with fentanyl and thiopental and maintained with nitrous
      oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was
      given for intubation. The ulnar nerve was stimulated, and the evoked
      electromyogram recorded using a Datex NMT monitor. RESULTS: Based on the response
      to the first of four stimuli, neither the lag time nor the onset-time differed
      between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and
      75% of the baseline response and the recovery index (RI, 25%-75%) were
      significantly shorter in patients on chronic carbamazepine therapy. CONCLUSIONS:
      The authors conclude that the duration of the rocuronium-induced neuromuscular
      block is significantly shortened by preceding chronic carbamazepine therapy.

PMID- 9915320
TI  - Reducing myoclonus after etomidate.
AB  - BACKGROUND: The authors hypothesized that myoclonus after etomidate is dose
      related, could be suppressed when small doses of etomidate were administered
      before induction, and is unassociated with seizure-like activity on
      electroencephalogram (EEG). METHODS: Three studies were performed. In the first
      study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100,
      0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were
      randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate
      or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for
      subjects in the first two studies. In a third study, 60 patients were randomly
      allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075
      mg/kg before 0.300 mg/kg was given. RESULTS: In Study 1, myoclonus was not
      observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after
      0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after
      0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related
      (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had
      mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05).
      EEG changes, other than delta waves, were not seen during myoclonic epochs. In
      Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or
      0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). CONCLUSIONS:
      Incidence and intensity of myoclonus after induction with etomidate are dose
      related, suppressed by pretreatment, and unassociated with seizure-like EEG
      activity.

PMID- 9915321
TI  - Dual actions of volatile anesthetics on GABA(A) IPSCs: dissociation of blocking
      and prolonging effects.
AB  - BACKGROUND: Volatile agents alter inhibitory postsynaptic currents (IPSCs) at
      clinically relevant concentrations, an action that is thought to make an
      important contribution to their behavioral effects. The authors investigated the
      mechanisms underlying these effects by evaluating the concentration dependence of
      modulation by enflurane, isoflurane, and halothane of IPSCs in rat hippocampal
      slices. METHODS: Action potential-independent gamma-aminobutyric acid(A) IPSCs
      (miniature IPSCs [mIPSCs]) were recorded from CA1 pyramidal neurons. The effects
      on mIPSC amplitude were used to distinguish between presynaptic (altered release)
      and postsynaptic (altered receptor response) actions of volatile agents. The
      concentration dependence of blocking and prolonging actions was compared among
      the volatile agents to determine whether a single modulatory process could
      account for both effects. RESULTS: The application of volatile anesthetics
      prolonged the decay and reduced the amplitude of mIPSCs in a dose-dependent
      manner. The effects on decay time for isoflurane and enflurane could not be
      distinguished. However, the blocking effect of enflurane was significantly
      greater than that of isoflurane at all concentrations. Despite the blocking
      effect, the net action of these agents was enhanced inhibition, because charge
      transfer was always significantly greater than control. Isoflurane, and to a
      lesser extent enflurane and halothane, caused a picrotoxin-sensitive increase in
      baseline noise. Moderate increases in mIPSC frequency were also observed for all
      agents. CONCLUSIONS: These results show that enflurane, isoflurane, and halothane
      reduce IPSC amplitude through a direct postsynaptic action. Furthermore, the
      concentration dependence of the actions of the agents reveals a dissociation
      between the effects on the amplitude and the time course of IPSCs, suggesting
      that distinct mechanisms underlie the two actions.

PMID- 9915322
TI  - Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine
      receptor.
AB  - BACKGROUND: Volatile general anesthetics increase agonist-mediated ion flux
      through the gamma-aminobutyric acid(A), glycine, and 5-hydroxytryptamine3 (5-HT3)
      receptors. This action reflects an anesthetic-induced increase in the apparent
      agonist affinity of these receptors. In contrast, volatile anesthetics block ion
      flux through the nicotinic acetylcholine receptor (nAcChoR). The authors tested
      the hypothesis that in addition to blocking ion flux through the nAcChoR,
      isoflurane also increases the apparent affinity of the nAcChoR for agonist.
      METHODS: Nicotinic acetylcholine receptors were obtained from the electroplax
      organ of Torpedo nobiliana. The apparent agonist affinity of the nAcChoR was
      determined using a new stopped-flow fluorescence assay. This assay derives the
      apparent agonist affinity of the nAcChoR from the apparent rates with which
      agonists convert nAcChoRs from the resting state to the desensitized state.
      RESULTS: Isoflurane significantly increased the apparent affinity (decreased the
      apparent dissociation constant) of acetylcholine for the nAcChoR at clinically
      relevant concentrations. The apparent dissociation constant decreased
      exponentially with the isoflurane concentration from a control value of 44+/-4
      microM to 1.0+/-0.1 microM in the presence of 1.5 mM isoflurane, the highest
      concentration studied. CONCLUSIONS: Isoflurane increases the apparent agonist
      affinity of the nAcChoR; however, this effect is poorly resolved in ion flux
      studies because isoflurane also causes channel blockade. The lack of saturation
      of isoflurane's effect on the apparent agonist affinity even at relatively high
      isoflurane concentrations argues against a single site of anesthetic action.
      However, it is consistent with isoflurane interactions with several receptor
      sites that exhibit a range of anesthetic affinities, sites within the membrane
      lipid, or both.

PMID- 9915323
TI  - Effects of sodium nitroprusside and phenylephrine on blood flow in free
      musculocutaneous flaps during general anesthesia.
AB  - BACKGROUND: Hypoperfusion and necrosis in free flaps used to correct tissue
      defects remain important clinical problems. The authors studied the effects of
      two vasoactive drugs, sodium nitroprusside and phenylephrine, which are used
      frequently in anesthetic practice, on total blood flow and microcirculatory flow
      in free musculocutaneous flaps during general anesthesia. METHODS: In a porcine
      model (n = 9) in which clinical conditions for anesthesia and microvascular
      surgery were simulated, latissimus dorsi free flaps were transferred to the lower
      extremity. Total blood flow in the flaps was measured using ultrasound flowmetry
      and microcirculatory flow was measured using laser Doppler flowmetry. The effects
      of sodium nitroprusside and phenylephrine were studied during local infusion
      through the feeding artery of the flap and during systemic administration.
      RESULTS: Systemic sodium nitroprusside caused a 30% decrease in mean arterial
      pressure, but cardiac output did not change. The total flow in the flap decreased
      by 40% (P < 0.01), and microcirculatory flow decreased by 23% in the skin (P <
      0.01) and by 30% in the muscle (P < 0.01) of the flap. Sodium nitroprusside
      infused locally into the flap artery increased the total flap flow by 20% (P <
      0.01). Systemic phenylephrine caused a 30% increase in mean arterial pressure,
      whereas heart rate, cardiac output, and flap blood flow did not change. Local
      phenylephrine caused a 30% decrease (P < 0.01) in the total flap flow.
      CONCLUSIONS: Systemic phenylephrine in a dose increasing the systemic vascular
      resistance and arterial pressure by 30% appears to have no adverse effects on
      blood flow in free musculocutaneous flaps. Sodium nitroprusside, however, in a
      dose causing a 30% decrease in systemic vascular resistance and arterial
      pressure, causes a severe reduction in free flap blood flow despite maintaining
      cardiac output.

PMID- 9915324
TI  - Ionic mechanisms mediating the differential effects of methohexital and
      thiopental on action potential duration in guinea pig and rabbit isolated
      ventricular myocytes.
AB  - BACKGROUND: Commonly used barbiturate anesthetics may significantly influence
      cardiac electrophysiologic characteristics. The authors evaluated thiopental (a
      thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar
      physicochemical properties but different structures, to determine whether they
      have distinct effects on the major ionic currents that determine action potential
      duration (APD) in ventricular myocytes. METHODS: The effects of thiopental and
      methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization
      were studied in guinea pig and rabbit single ventricular myocytes using the patch
      clamp technique in a whole-cell configuration. The ionic mechanisms underlying
      the APD changes were evaluated by measuring the anesthetics' effects on the L
      type calcium inward current, the inward rectifier potassium current, and the
      delayed rectifier potassium current in guinea pig cells and on the transient
      outward potassium current in rabbit cells. RESULTS: Thiopental and methohexital
      caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in
      guinea pig and rabbit ventricular myocytes, methohexital shortened them.
      Thiopental markedly depressed both the inward and outward components of the
      inward rectifier potassium current, whereas methohexital caused minimal
      inhibition of the inward component and no change in the outward component. The
      delayed rectifier potassium current was inhibited by thiopental but significantly
      potentiated by methohexital. Neither thiopental nor methohexital significantly
      affected the transient outward potassium current or the L-type calcium inward
      current. CONCLUSIONS: Despite their similar lipid solubilities, molecular
      weights, and pKa values, thiopental increased and methohexital decreased the APD
      in ventricular myocytes by predominantly inhibiting the inward rectifier
      potassium current and the delayed rectifier potassium current and by increasing
      the delayed rectifier potassium current, respectively. These characteristics
      suggest distinct structure-specific actions of barbiturates on the function of
      myocardial ionic channels.

PMID- 9915325
TI  - Spinal action of ketorolac, S(+)- and R(-)-ibuprofen on non-noxious activation of
      the catechol oxidation in the rat locus coeruleus: evidence for a central role of
      prostaglandins in the strychnine model of allodynia.
AB  - BACKGROUND: Blockade of spinal glycine receptors with intrathecal strychnine
      produces an allodynia-like state in the anesthetized rat. Innocuous hair
      deflection in the presence of intrathecal strychnine induces a nociceptive-like
      activation of catechol oxidation in the locus coeruleus and enhances
      cardiovascular responses. Because prostaglandins play a central role in
      augmenting pain, this study evaluated the effect of intrathecal nonsteroidal
      antiinflammatory drugs in strychnine-induced allodynia. METHODS: In urethane
      anesthetized rats, changes in catechol oxidation in the locus coeruleus, measured
      using in vivo voltammetry, and cardiovascular parameters evoked by hair
      deflection of caudal dermatomes were determined after strychnine (40 microg) or
      saline were administered intrathecally. Subsequently, the effects of 30 microg
      ketorolac, 10 microg S(+)-ibuprofen, and 10 microg R(-)-ibuprofen administered
      intrathecally were evaluated. RESULTS: After strychnine was administered
      intrathecally, hair deflection evoked an increase in the locus coeruleus catechol
      oxidation (peak, 149.7+/-7.2% of baseline) and mean arterial blood pressure
      (peak, 127.5+/-3.8% of baseline). These responses were not observed after saline
      was administered intrathecally. All hair deflection-evoked, strychnine-dependent
      peak responses were attenuated significantly with intrathecally administered
      ketorolac and S(+)-ibuprofen but not with R(-)-ibuprofen. CONCLUSIONS: Locus
      coeruleus catechol oxidation is a sensitive biochemical index of strychnine
      induced allodynia and is correlated temporally with the cardiovascular responses
      evoked by hair deflection during spinal glycinergic inhibition. The ability of
      intrathecally administered ketorolac and S(+)-ibuprofen, but not R(-)-ibuprofen,
      to suppress the locus coeruleus catechol oxidation and cardiovascular peak
      responses evoked during strychnine-induced allodynia provide evidence that
      central prostaglandins play an important role in the abnormal sensory processing
      of strychnine-induced allodynia.

PMID- 9915326
TI  - Stereoselective interaction of ketamine with recombinant mu, kappa, and delta
      opioid receptors expressed in Chinese hamster ovary cells.
AB  - BACKGROUND: The authors examined the interaction of ketamine with recombinant mu,
      kappa, and delta opioid receptors and recombinant orphan opioid receptors
      expressed in Chinese hamster ovary cells (CHO-mu, CHO-kappa, CHO-delta, and
      CHO(ORL1), respectively). METHODS: CHO-mu, CHO-kappa, and CHO-delta membranes
      were incubated with the opioid receptor radioligand [3H]diprenorphine at room
      temperature. Ketamine (racemic, R(-) and S(+)) was included at concentrations
      covering the clinical range. CHO(ORL1) membranes were incubated with
      [125I]Tyr(14)nociceptin and racemic ketamine at room temperature. The effects of
      racemic ketamine and selective opioid receptor agonists (mu: [D-Ala2, MePhe4,
      Gly(ol)5] enkephalin (DAMGO); kappa: spiradoline or delta: [D-pen2, D-pen5]
      enkephalin (DPDPE)) on forskolin-stimulated cyclic adenosine monophosphate
      formation also were examined. Data are mean +/- SEM. RESULTS: Racemic ketamine
      increased the radioligand equilibrium dissociation constant for [3H]diprenorphine
      from 85+/-5 to 273+/-11, 91+/-6 to 154+/-16, and 372+/-15 to 855+/-42 pM in CHO
      mu, CHO-kappa, and CHO-delta, respectively. The concentration of radioligand
      bound at saturation was unaffected. In CHO-mu and CHO-kappa cells, racemic
      ketamine did not slow the rate of naloxone-induced [3H]diprenorphine
      dissociation. Ketamine and its isomers also displaced [3H]diprenorphine binding
      to mu, kappa, and delta receptors in a dose-dependent manner, with pKi values for
      racemic ketamine of 4.38+/-0.02, 4.55+/-0.04, and 3.57+/-0.02, respectively. S(+)
      ketamine was two to three times more potent than R(-)-ketamine at mu and kappa
      receptors. Racemic ketamine displaced [125I]Tyr(14)nociceptin with an estimated
      affinity constant of 0.5 mM. Racemic ketamine inhibited the formation of cyclic
      adenosine monophosphate (naloxone insensitive) in a dose-dependent manner
      (concentration producing 50% inhibition approximately 2 mM) in all cell lines,
      including untransfected CHO cells. Ketamine (100 microM) reversed DAMGO (mu) and
      spiradoline (kappa) inhibition of formation of cyclic adenosine monophosphate.
      CONCLUSIONS: Ketamine interacts stereoselectively with recombinant mu and kappa
      opioid receptors.

PMID- 9915327
TI  - Quantification and distribution of cerebral emboli during cardiopulmonary bypass
      in the swine: the impact of PaCO2.
AB  - BACKGROUND: Patients undergoing cardiac surgery have a substantial incidence of
      neurologic complications related to cerebral embolization during cardiopulmonary
      bypass. The purpose of this study was to determine if adjustments in the arterial
      carbon dioxide (PaCO2) level can reduce cerebral and ocular embolization.
      METHODS: Twenty pigs underwent cardiopulmonary bypass at 38 degrees C. At either
      hypercarbia (PaCO2 = 50-55 mmHg, group H, n = 10) or hypocarbia (PaCO2 = 25-30
      mmHg, group L, n = 10), an embolic load of 1.2 x 10(50 67-microm orange
      fluorescent microspheres was injected into the aortic cannula. Before and after
      embolization, cerebral and ocular blood flows were determined at normocapnia
      using 15-microm fluorescent microspheres. After cardiopulmonary bypass was
      completed, the eyes were enucleated and brain tissue samples were collected.
      Microspheres were isolated and the fluorescence was measured. RESULTS: In groups
      H and L, the mean PaCO2 values at embolization were 52+/-3 mmHg and 27+/-2 mmHg,
      respectively (P < 0.0001). Total and regional embolization were significantly
      less in hypocapnia than in hypercapnic animals: 142% more emboli were detected in
      the brain in group H than in group L (P < 0.0001). Cerebral blood flow after
      embolization was unchanged in both groups. Similarly, fewer ocular emboli
      occurred in hypocapnic animals than in hypercapnic animals (P = 0.044), but in
      contrast to the brain, ocular blood flow decreased significantly in both groups
      after embolization. CONCLUSIONS: Cerebral embolization is determined by the PaCO2
      at the time of embolization. In cardiopulmonary bypass practice, reductions in
      PaCO2 during periods of embolic risk may reduce the risk for brain injury.

PMID- 9915328
TI  - Effect of nonsedative doses of propofol on an innate anxiogenic situation in
      rats.
AB  - BACKGROUND: The effect of propofol on anxiety has not been well studied. In
      humans, such investigations are confused by the fact that sedation often coexists
      with anxiolysis. Therefore, the authors evaluated the effects of minimal sedation
      with propofol in rats placed in an innate anxiogenic situation, the elevated plus
      shaped maze. METHODS: In experiment 1, spontaneous locomotor activity was
      determined in rats as a measure of sedative effect induced by propofol (0-9 mg/kg
      administered intraperitoneally). In experiment 2, groups of rats received
      propofol (0-9 mg/kg) or diazepam (0-2 mg/kg) and then were placed on a plus
      shaped maze elevated above the ground that was composed of two opposite closed
      arms and two opposite open arms. On an initial exposure to the maze, undrugged
      rats avoid the open arms, with the number of entries into and time spent within
      the open arms constituting approximately 20% of their total activity. This
      reflects normal anxiety in a rodent for any elevated open platform. RESULTS: In
      experiment 1, 0-9 mg/kg propofol did not alter spontaneous activity in rats. In
      experiment 2, propofol and diazepam significantly increased the number of entries
      into and the time spent within the open arms. Propofol at a dose of 9 mg/kg
      significantly increased the rats' level of exploration of the open arms to about
      50% of all exploratory activity, and a similar observation was made with 2 mg/kg
      diazepam. CONCLUSIONS: In a standard animal model, propofol has anxiolytic
      properties at doses that do not produce sedation.

PMID- 9915329
TI  - Inhibitory effects of diazepam and midazolam on Ca2+ and K+ channels in canine
      tracheal smooth muscle cells.
AB  - BACKGROUND: Benzodiazepines have a direct bronchodilator action in airway smooth
      muscle, but the mechanisms by which these agents produce muscle relaxation are
      not fully understood. The current study was performed to identify the effects of
      the benzodiazepines diazepam and midazolam on Ca2+ and K+ channels in canine
      tracheal smooth muscle cells. METHODS: Whole-cell patch-clamp recording
      techniques were used to evaluate the effects of the benzodiazepines diazepam (10(
      8) to 10(-3) M) and midazolam (10(-8) to 10(-3) M) on inward Ca2+ and outward K+
      channel currents in dispersed canine tracheal smooth muscle cells. The effects of
      the antagonists flumazenil (10(-5) M) and PK11195 (10(-5) M) on these channels
      were also studied. RESULTS: Each benzodiazepine tested significantly inhibited
      Ca2+ currents in a dose-dependent manner, with 10(-6) M diazepam and 10(-5) M
      midazolam each causing approximately 50% depression of peak voltage-dependent
      Ca2+ currents. Both benzodiazepines promoted the inactivated state of the channel
      at more-negative potentials. The Ca2+-activated and voltage-dependent K+ currents
      were inhibited by diazepam and midazolam (> 10(-5) M and > 10(-4) M,
      respectively). Flumazenil and PK11195 had no effect on these channel currents or
      on the inhibitory effects of the benzodiazepines. CONCLUSIONS: Diazepam and
      midazolam had inhibitory effects on voltage-dependent Ca2+ channels, which lead
      to muscle relaxation. However, high concentrations of these agents were necessary
      to inhibit the K+ channels. The lack of antagonized effects of their antagonists
      is related to the non-gamma-aminobutyric acid-mediated electrophysiologic effects
      of benzodiazepines on airway smooth muscle contractility.

PMID- 9915330
TI  - Increasing isoflurane from 0.9 to 1.1 minimum alveolar concentration minimally
      affects dorsal horn cell responses to noxious stimulation.
AB  - BACKGROUND: The spinal cord appears to be the site at which isoflurane suppresses
      movement that occurs in response to a noxious stimulus. In an attempt to localize
      its site of suppressant action, the authors determined the effect of isoflurane
      on dorsal horn neuronal responses to supramaximal noxious stimulation at end
      tidal concentrations that just permitted and just prevented movement. METHODS:
      Rats (n = 14) were anesthetized with isoflurane, and after lumbar laminectomy,
      the minimum alveolar concentration (MAC) for each rat was determined using a
      supramaximal mechanical stimulus. In these same rats, after extracellular
      microelectrode placement in the lumbar spinal cord, dorsal horn neuronal
      responses to the supramaximal stimulus were determined at the concentrations of
      isoflurane that bracketed each rat's MAC (0.1% higher and lower than MAC). The
      MAC of isoflurane was then re-determined. RESULTS: Dorsal horn neuronal response
      was 1,757+/-892 impulses/min at 0.9 MAC and 1,508+/-988 impulses/min at 1.1 MAC,
      a 14% decrease (P < 0.05). Cell responses varied, with some cells increasing
      their response at the higher concentration of isoflurane. The MAC of isoflurane
      was 1.38+/-0.2% before and 1.34+/-0.2% after determination of dorsal horn
      neuronal responses. CONCLUSIONS: Isoflurane, at concentrations that bracket MAC,
      has a variable and minimal depressant effect on dorsal horn cell responses to
      noxious mechanical stimulation. These data suggest that the major action of
      isoflurane to suppress movement evoked by a noxious stimulus might occur
      primarily at a site other than the dorsal horn.

PMID- 9915331
TI  - Effect of propofol on arachidonate cascade by vasopressin in aortic smooth muscle
      cells: inhibition of PGI2 synthesis.
AB  - BACKGROUND: The mechanisms underlying the vascular effects of propofol are not
      fully understood. Vasopressin, a potent vasoactive peptide, stimulates the
      arachidonate cascade and the synthesis of prostacyclin (PGI2; the main metabolite
      of the cascade in vascular smooth muscle cells). Arachidonic acid (AA) release by
      phospholipases is the rate-limiting step in the cascade. We investigated the
      mechanisms underlying vasopressin-induced AA release and the effect of propofol
      on PGI2 synthesis in a rat aortic smooth muscle cell line: A10 cells. METHODS: In
      cultured A10 cells pretreated with propofol, the stimulation by vasopressin of AA
      release and PGI2 synthesis was evaluated by measuring [3H]AA and 6-keto
      PGF1alpha, respectively, in the culture medium. The effects of propofol on
      vasopressin-induced activation of phosphoinositide-hydrolyzing phospholipase C
      and phosphatidylcholine-hydrolyzing phospholipase D were evaluated by measuring
      inositol phosphate formation and choline formation, respectively. RESULTS: A
      phospholipase C inhibitor and a phosphatidic acid phosphohydrolase inhibitor both
      attenuated vasopressin-induced AA release and PGI2 synthesis, as did a
      phospholipase A2 inhibitor. Propofol inhibited vasopressin-induced activation of
      phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing
      phospholipase D, but this effect of propofol was significant only at
      supraclinical concentration (0.1 mM). Propofol reduced vasopressin-induced PGI2
      synthesis. The inhibitory effect was observed at concentrations (10 microM-0.1
      mM) higher than those used clinically. CONCLUSIONS: Propofol suppresses the
      arachidonate cascade caused by vasopressin at least partly by inhibiting
      phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing
      phospholipase D, resulting in the inhibition of PGI2 synthesis. Propofol-mediated
      inhibition of vasopressin-stimulated synthesis of PGI2 may reduce the
      vasorelaxation by propofol.

PMID- 9915332
TI  - Characterization of the antihyperalgesic action of a novel peripheral mu-opioid
      receptor agonist--loperamide.
AB  - BACKGROUND: Preclinical and clinical evidence indicates that locally administered
      opioid agonists produce an antihyperalgesic effect through peripheral opioid
      receptors in inflamed tissue. Loperamide, a mu opioid agonist, does not cross the
      blood-brain barrier and therefore lacks central effects after systemic
      administration. The authors defined the effects of topical loperamide on a
      thermal injury-induced hyperalgesia. METHODS: In halothane-anesthetized rats,
      thermal injury was induced by placing the plantar surface of a hindpaw on a hot
      plate (52.0+/-1 degrees C) for 45 s. Loperamide was prepared in a cream emulsion
      (ADL 2-1294B, 0.5%, 1.7%, and 5.0%). The drug was applied as follows: before or
      after injury on the injured paw and on a normal paw and after injury on the
      injured paw of morphine-tolerant rats. Paw withdrawal latency to a radiant heat
      source was measured to determine the nociceptive threshold. A pharmacokinetic
      study was performed with the use of 14C-labeled drug. RESULTS: Thermal injury
      yielded a significant thermal hyperalgesia. Loperamide, but not the vehicle,
      posttreatment on the injured paw resulted in a dose-dependent antihyperalgesic
      effect, which was reversible with naloxone (1 mg/kg given intraperitoneally).
      Treatment with loperamide on the normal paw produced short-lasting hypoalgesia,
      but the effect was not reversible with naloxone. Pretreatment at 1 and 2 but not
      4 h with loperamide was effective. A rightward shift of the dose-response curve
      was observed in rats made tolerant to systemic morphine with subcutaneous
      morphine pellets. No rats with drug treatment displayed any evident behavior
      changes (eg., loss of corneal or pinna reflexes or change in ambulation). Drug
      activity in the tissue revealed an elimination half life of 2.3 h and negligible
      concentration in the blood. CONCLUSIONS: Loperamide, a peripherally acting mu
      opioid agonist, applied topically at the site of inflammation possesses a
      significant antihyperalgesic action without any systemic side effects.

PMID- 9915333
TI  - Bound volatile general anesthetics alter both local protein dynamics and global
      protein stability.
AB  - BACKGROUND: Recent studies have demonstrated that volatile general anesthetic
      agents such as halothane and isoflurane may bind to discrete sites on protein
      targets. In the case of bovine serum albumin, the sites of halothane and
      chloroform binding have been identified as being located in the IB and IIA
      subdomains. This structural information provides a foundation for more detailed
      studies into the potential mechanisms of anesthetic action. METHODS: The effect
      of halothane and isoflurane and the nonimmobilizer 1,2
      dichlorohexafluorocyclobutane on the mobility of the indole ring in the
      tryptophan residues of albumin was investigated using measurements of
      fluorescence anisotropy. Myoglobin served as a negative control. In addition, the
      effect of bound anesthetic agents on global protein stability was determined by
      thermal denaturation experiments using near-ultraviolet circular dichroism
      spectroscopy. RESULTS: The fluorescence anisotropy measurements showed that
      halothane and isoflurane decreased the mobility of the indole rings in a
      concentration-dependent manner. The calculated dissociation constants were 1.6+/
      0.4 and 1.3+/-0.3 mM for isoflurane and halothane, respectively. In contrast,
      both agents failed to increase the fluorescence anisotropy of the tryptophan
      residues in myoglobin, compatible with lack of binding. The nonimmobilizer 1,2
      dichlorohexafluorocyclobutane caused no change in the fluorescence anisotropy of
      albumin. Binding of the anesthetic agents stabilized the native folded form of
      albumin to thermal denaturation. Analysis of the thermal denaturation data
      yielded dissociation constant values of 0.98+/-0.10 mM for isoflurane and 1.0+/
      0.1 mM for halothane. CONCLUSIONS: Attenuation of local side-chain dynamics and
      stabilization of folded protein conformations may represent fundamental modes of
      action of volatile general anesthetic agents. Because protein activity is
      crucially dependent on inherent flexibility, anesthetic-induced stabilization of
      certain protein conformations may explain how these important clinical agents
      change protein function.

PMID- 9915334
TI  - Sevoflurane selectively increases coronary collateral blood flow independent of
      KATP channels in vivo.
AB  - BACKGROUND: Volatile anesthetic agents produce coronary vasodilation via
      activation of adenosine triphosphate-sensitive potassium (KATP) channels. The
      authors tested the hypothesis that sevoflurane selectively increases coronary
      collateral blood flow and assessed the role of KATP channel activation in this
      process. METHODS: Experiments were conducted in dogs 8 weeks after long-term
      implantation of a left anterior descending coronary artery (LAD) ameroid
      constrictor to stimulate coronary collateral growth. Dogs were instrumented for
      measurement of retrograde LAD blood flow (an index of large coronary collateral
      blood flow) and LAD tissue flow (via radioactive microspheres; an index of small
      collateral blood flow). Coronary collateral perfusion and normal (left circumflex
      coronary artery [LCCA]) zone tissue blood flow were determined in four groups of
      dogs pretreated with intracoronary glyburide (50 microg/kg) or vehicle in the
      presence or absence of sevoflurane (1 minimum alveolar concentration). Dose
      response relationships to the KATP channel agonist nicorandil were established in
      each dog using doses (25, 50, and 100 microg/min) previously shown to increase
      coronary collateral blood flow. RESULTS: Sevoflurane increased blood flow through
      large and small collaterals and increased collateral vascular conductance in the
      presence of glyburide but did not affect LCCA blood flow or conductance. In
      contrast, nicorandil increased blood flow through small but not large
      collaterals. Nicorandil also increased LCCA blood flow and conductance, actions
      that were attenuated by glyburide. CONCLUSIONS: The results demonstrate that
      sevoflurane selectively increases large and small coronary collateral blood flow
      via mechanism(s) independent of KATP channel activation.

PMID- 9915335
TI  - A cost-construction model to assess the total cost of an anesthesiology residency
      program.
AB  - BACKGROUND: Although the total costs of graduate medical education are difficult
      to quantify, this information may be of great importance for health policy and
      planning over the next decade. This study describes the total costs associated
      with the residency program at the University of Texas--Houston Department of
      Anesthesiology during the 1996-1997 academic year. METHODS: The authors used cost
      construction methodology, which computes the cost of teaching from information on
      program description, resident enrollment, faculty and resident salaries and
      benefits, and overhead. Surveys of faculty and residents were conducted to
      determine the time spent in teaching activities; access to institutional and
      departmental financial records was obtained to quantify associated costs. The
      model was then developed and examined for a range of assumptions concerning
      resident productivity, replacement costs, and the cost allocation of activities
      jointly producing clinical care and education. RESULTS: The cost of resident
      training (cost of didactic teaching, direct clinical supervision, teaching
      related preparation and administration, plus the support of the teaching program)
      was estimated at $75,070 per resident per year. This cost was less than the
      estimated replacement value of the teaching and clinical services provided by
      residents, $103,436 per resident per year. Sensitivity analysis, with different
      assumptions regarding resident replacement cost and reimbursement rates, varied
      the cost estimates but generally identified the anesthesiology residency program
      as a financial asset. CONCLUSIONS: In most scenarios, the value of the teaching
      and clinical services provided by residents exceeded the cost of the resources
      used in the educational program.

PMID- 9915336
TI  - Psychotropic drugs used in anesthesia practice: abuse liability and epidemiology
      of abuse.

PMID- 9915338
TI  - Cerebral infarction after deflation of a pneumatic tourniquet during total knee
      replacement.

PMID- 9915337
TI  - DNR in the OR: a goal-directed approach.

PMID- 9915339
TI  - The perioperative management of portopulmonary hypertension with nitric oxide and
      epoprostenol.

PMID- 9915340
TI  - Dual capnography facilitates detection of a critical perfusion defect in an
      individual lung.

PMID- 9915341
TI  - Simultaneous transesophageal echocardiography and atrial pacing for
      intraoperative management of mitral regurgitation.

PMID- 9915342
TI  - Cannulation of the cervical epidural venous plexus: a rare complication of
      retrograde internal jugular vein catheterization.

PMID- 9915343
TI  - Cranial nerve X and XII paralysis (Tapia's syndrome) after an interscalene
      brachial plexus block for a left shoulder Mumford procedure.

PMID- 9915344
TI  - Abrupt onset of adrenal crisis during routine preoperative examination in a
      patient with unknown Addison's disease.

PMID- 9915345
TI  - Transient hypotension as a complication of monitoring transcervical motor evoked
      potentials.

PMID- 9915346
TI  - The spinal inquisition: heresy of neurotaxonomy.

PMID- 9915347
TI  - The use of magnetic resonance imaging in patients with fiberoptic intracranial
      pressure monitors.

PMID- 9915348
TI  - Studies' divergent results.

PMID- 9915349
TI  - Rate of injection and neurotoxicity of spinal lidocaine.

PMID- 9915350
TI  - Shearing of plastic coating of stylet with double lumen tube: another incident.

PMID- 9915351
TI  - Bottle contamination.

PMID- 9915352
TI  - Does anesthesia permanently alter brain biochemistry?

PMID- 9915353
TI  - Benchmarking anesthesia costs.

PMID- 9915354
TI  - Cost per unit.

PMID- 9915355
TI  - Critical hemoglobin desaturation can be delayed by apneic diffusion oxygenation.

PMID- 9915356
TI  - Catecholamine surge in opioid-addicted patients undergoing detoxification under
      general anesthesia.

PMID- 9915357
TI  - Possible mechanism(s) of opioid-induced coughing.

PMID- 9915358
TI  - The window that is opened by optical isomers.

PMID- 9915359
TI  - A helpful approach to repositioning patients.

PMID- 9915360
TI  - ACCRI: "Anesthesia and critical care resources on the Internet".

PMID- 9915361
TI  - The modified bitegard: a method for administering supplemental oxygen and
      measuring carbon dioxide.

PMID- 9915362
TI  - Tuohy needle and loss of resistance technique: a safer approach for
      thoracentesis.

PMID- 9915363
TI  - Perioperative extrapyramidal reactions associated with ondansetron.

PMID- 9915364
TI  - Extubating the difficult airway--an unusual role for a Fogarty catheter.

PMID- 9915365
TI  - The 31st Walter J. Zeiter Lecture. Issues and challenges for physiatry in the
      coming decade.

PMID- 9915366
TI  - Long-term continuously infused intrathecal baclofen for spastic-dystonic
      hypertonia in traumatic brain injury: 1-year experience.
AB  - OBJECTIVE: To determine if the long-term use of continuously infused intrathecal
      baclofen (ITB) over a 1-year period will control spastic-dystonic hypertonia in
      patients with traumatic brain injury (TBI). SETTING: Tertiary care outpatient and
      inpatient rehabilitation center directly attached to a university hospital.
      SUBJECTS: Persons with TBI and intractable spasticity and dystonia for more than
      6 months' duration recruited in a consecutive manner. DESIGN: TBI patients were
      admitted to the study after screening via a bolus injection of either intrathecal
      normal saline or 50 microg of baclofen. Data for Ashworth rigidity scores, spasm
      scores, and deep tendon reflex scores were collected for both the upper
      extremities (UE) and lower extremities (LE). Patients whose LE Ashworth scores
      decreased an average of 2 points were then offered implantation of a computer
      controlled pump for continuous ITB. Changes over time were assessed statistically
      via Friedman's analysis for ordinal data and ANOVA for linear data. Differences
      between set points in time were also assessed via Wilcoxon signed rank. DATA SET:
      Seventeen patients (average age 29+/-11 yrs) with spasticity and/or dystonia
      treated over 1 year via a computer-controllable intrathecal delivery system for
      the delivery of ITB. RESULTS: After 1 year of continuous ITB treatment the
      average LE Ashworth score decreased from 3.5+/-1.3 (SD) to 1.7+/-0.9 (p < .0001),
      spasm score from 1.8+/-1.3 to 0.2+/-0.5 (p< .0001), and reflex score from 2.5+/
      1.1 to 0.1+/-0.3 (p < .0001). The average UE Ashworth score decreased from 2.9+/
      1.5 to 1.6+/-1.0 (p < .0001), spasm score from 1.2+/-1.5 to 0.2+/-0.6 (p <
      0.0001), and reflex score from 2.2+/-0.5 to 1.0+/-0.8 (p < .0001). The average
      ITB dose required to attain these effects at 1 year was 302 microg continuously
      infused per day. CONCLUSION: Continuous intrathecal infusion of baclofen is
      capable of maintaining a reduction in spasticity and dystonia in both the upper
      and lower extremities of TBI patients.

PMID- 9915367
TI  - Can spinal surgery be prevented by aggressive strengthening exercises? A
      prospective study of cervical and lumbar patients.
AB  - OBJECTIVE: To determine if patients recommended for spinal surgery can avoid the
      surgery through an aggressive strengthening program. SETTING: A privately owned
      clinic, staffed by physicians and physical therapists, that provides treatment
      for patients with neck and/or back pain. METHODS: Over a period of 2 1/2 years,
      consecutive patients referred to the clinic for evaluation and treatment were
      enrolled in the study if they (1) had a physician's recommendation for lumbar or
      cervical surgery, (2) had no medical condition preventing exercise, and (3) were
      willing to participate in the approximately 10-week outpatient program. Treatment
      consisted mainly of intensive, progressive resistance exercise of the isolated
      lumbar or cervical spine. Exercise was continued to failure, and patients were
      encouraged to work through their pain. Third-party payors in Minneapolis were
      surveyed for average costs. Average follow-up occurred 16 months after discharge.
      RESULTS: Forty-six of the 60 participants completed the program; 38 were
      available for follow-up and three required surgery after completing the program.
      DISCUSSION/CONCLUSIONS: Despite methodologic limitations, the results are
      intriguing. A large number of patients who had been told they needed surgery were
      able to avoid surgery in the short term by aggressive strengthening exercise.
      This study suggests the need to define precisely what constitutes "adequate
      conservative care."

PMID- 9915368
TI  - The influence of stance-phase knee flexion on the vertical displacement of the
      trunk during normal walking.
AB  - OBJECTIVE: To determine the effect of stance-phase knee flexion on the trunk's
      vertical displacement in normal walking. SUBJECTS: Three able-bodied adult male
      volunteers. DESIGN: Kinematic data describing the joint centers and joint angles
      of the legs and pelvis were collected from the subjects. The subjects walked at
      four target speeds (range, approximately 1.0 to 2.0 m/sec); a minimum of three
      trials of data at each walking speed were collected and processed. SETTING:
      Clinical gait analysis laboratory. RESULTS: Stance-phase knee flexion was not
      found to significantly reduce the peak-to-peak amplitude of the trunk's vertical
      displacement in normal walking. The reason for this has to do with the timing
      (ie, phase) of the stance-phase knee flexion wave with respect to the trunk's
      vertical displacement during the gait cycle. Stance-phase knee flexion in normal
      walking was found to reduce the mean elevation of the trunk by a few millimeters
      and to delay the trunk's vertical displacement waveform by about 2% to 6% of the
      gait cycle from where it would have been otherwise. CONCLUSIONS: Contrary to
      conventional wisdom, stance-phase knee flexion does not appreciably reduce the
      amount of vertical movement of the trunk in normal walking.

PMID- 9915369
TI  - Somatosensory and motor evoked potentials at different stages of recovery from
      severe traumatic brain injury.
AB  - OBJECTIVE: To detect changes of somatosensory evoked potentials (SEPs) and motor
      evoked potentials (MEPs) at different stages of recovery from severe brain injury
      and to determine whether they can be used to predict late functional outcome.
      DESIGN: Correlational study on a prospective cohort. SETTING: Brain injury
      rehabilitation center. PATIENTS: Twenty-seven consecutively sampled patients with
      severe traumatic brain injury referred to the inpatient intensive rehabilitation
      unit of primary care in a university-based system. MAIN OUTCOME MEASURES: (1)
      Glasgow Outcome Scale, Disability Rating Scale, and Functional Independence
      Measure; (2) SEPs and MEPs from upper limbs (ULs) and lower limbs (LLs). Outcome
      was assessed at 6 and 12 months after trauma. Correlations were computed with the
      nonparametric test of Spearman-Rank. RESULTS: Both SEPs and MEPs showed dynamic
      changes (p < .02 for N20, p < .05 for N30, P40, and N45), with a trend toward a
      progressive normalization. N30 was more frequently abnormal than N20. SEPs from
      LLs were more frequently and more persistently abnormal than those from ULs.
      Clinical and functional outcome was strongly correlated with the degree of
      abnormality of SEPs from LLs (p < .002), whereas only mild relationships were
      found with SEPs from ULs. Both SEPs and MEPs showed a high negative predictive
      value (83% for N30 and 83% for P40), but only SEPs from LLs also had a high
      positive predictive value (72% for P40). Sensitivity was 88% both for N30 and
      P40. Specificity was 50% for N30 and 70% for P40). CONCLUSION: SEPs from LLs can
      be very useful in monitoring the postacute phase of traumatic brain injury and in
      identifying patients who require further intensive rehabilitation. MEPs may be of
      questionable value.

PMID- 9915370
TI  - Hybrid functional electrical stimulation for energy-efficient restoration of
      standing-up motion.
AB  - OBJECTIVE: To find the most energy-efficient standing-up motion for quadriceps
      and to restore that motion in a person with complete paraplegia by using hybrid
      functional electrical stimulation. DESIGN: Nonrandomized control trial. SETTING:
      A referral center and institutional practice providing outpatient care.
      PARTICIPANTS: Twenty-nine volunteer samples were used to collect normal data. One
      patient with complete paraplegia received treatment for the restoration of
      standing-up motion. MAIN OUTCOME MEASUREMENTS: Joint angles and ground reaction
      forces were investigated during the standing-up motion with arms crossed in front
      of the chest with an ankle-foot orthosis set at various angles. The
      electromyogram (EMG) was performed during the standing-up motion with and without
      the orthosis. The energy costs of quadriceps during the standing-up motion were
      calculated using a mathematical model. Standing-up motion in a person with
      complete paraplegia was restored and then analyzed by measuring the vertical
      ground reaction force and the hip and knee angles. RESULTS: Quadriceps energy
      cost was lowest (p < .05) in subjects wearing the ankle-foot orthosis set at
      neutral with a flat sole line. In the integrated EMG the peak value of rectus
      femoris contraction was larger with the orthosis than without it (p < .05). A
      patient with complete paraplegia was able to stand up smoothly from a wheelchair
      based on stimulation patterns obtained from healthy subjects. CONCLUSIONS: Energy
      efficient standing-up motion in a patient with complete paraplegia was restored
      when the patient used an ankle-foot orthosis set at neutral with a flat sole
      line.

PMID- 9915371
TI  - Muscle fatigue from intermittent stimulation with low and high frequency
      electrical pulses.
AB  - OBJECTIVE: To evaluate muscle fatigue resulting from intermittent low frequency
      and high frequency stimulation for the application of closed-loop control in
      functional electrical stimulation (FES). DESIGN: Nonrandomized trial. SETTING:
      General community, a referral center, institutional practice, and ambulatory
      care. PATIENTS: Twenty healthy nondisabled men volunteered for the normal muscle
      group. Four paraplegic men with implanted percutaneous intramuscular electrodes
      for FES volunteered for the paralyzed muscle group. INTERVENTION: The stimulation
      frequency was set at low (20 Hz) or high (100 Hz). Stimulation was administered
      in 4-second bursts at the start of 60-second, 120-second, and 240-second periods
      (duty cycles of 1/15, 1/30, and 1/60, respectively). MAIN OUTCOME MEASUREMENTS:
      Knee extensor torques were measured during intermittent electrical stimulation. A
      strength decrement index (SDI) was used to assess muscle fatigue. Actual knee
      extensor torques in the paraplegic men were also measured with an isokinetic
      dynamometer. RESULTS: Muscle fatigue was significantly greater at 20 Hz than at
      100 Hz for both the nondisabled and the paraplegic subjects (p < .0001). Muscle
      fatigue at the 1/15 cycle was significantly reduced (p < .01). CONCLUSIONS:
      Muscle fatigue was greater at the lower frequency (20 Hz) than at the higher
      frequency (100 Hz) during intermittent electrical stimulation, suggesting that
      intermittent high frequency stimulation may be valuable in the development of
      closed-loop control strategies for FES.

PMID- 9915372
TI  - Muscle strength in the elderly: its relation to vitamin D metabolites.
AB  - OBJECTIVE: To identify a relation between loss of muscle strength and vitamin D
      deficiency in ambulatory elderly persons not receiving vitamin D supplementation.
      DESIGN: Cross-sectional study. SETTING: All measurements were taken at the
      Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS:
      Three hundred nineteen patients (103 women, 216 men) selected by random sampling
      from participants in an ongoing interdisciplinary study on aging (mean age for
      women, 74.2 yrs; for men, 76.7 yrs). OUTCOME MEASURES: Leg extension power (LEP)
      and body mass index (BMI); serum values of 25-hydroxyvitamin D [calcidiol,
      25(OH)D], 1,25-hydroxyvitamin D [calcitriol, 1,25(OH)2D], and intact parathyroid
      hormone (iPHT). RESULTS: Twelve percent of women and 18% of men had 25(OH)D
      values below the normal range (<12 ng/mL). Muscle strength was lower in older
      subjects (female: r = -.35; p = .0005/male: r = -.48; p < .0001) and was lower in
      women than in men (p < .0001). In men both 25(OH)D and 1,25(OH)2D was
      significantly correlated with LEP (r = 0.24; p = .0004/r = .14; p = .045). In
      women, only 1,25(OH)2D was significantly correlated with LEP (r = 0.22; p =
      .034). In an ANCOVA including all participants and explaining LEP by sex, age,
      BMI, 1,25(OH)2D, 25(OH)D, and iPTH, all factors showed significant effects except
      25(OH)D and iPTH (r2 = .41). CONCLUSION: Muscle strength declined with age in
      ambulatory elderly people and showed modest, but significant, positive
      correlation with 1,25(OH)2 vitamin D in both sexes and with 25(OH)D in male
      subjects. Therefore vitamin D deficiency appears to contribute to the age-related
      loss of muscle strength, which might be more pronounced in institutionalized
      elderly people with a high prevalence of vitamin D deficiency.

PMID- 9915373
TI  - Analysis of gait abnormalities in Huntington disease.
AB  - OBJECTIVE: To evaluate patterns of successful gait strategy in Huntington disease
      (HD) at various stages of illness to improve fall avoidance and maintenance of
      independence. DESIGN: Repeated measurements of gait kinematic parameters and
      joint performance during gait cycles of six HD patients compared to 30 age
      matched controls. SETTING: A standard gait laboratory. SUBJECTS: Six HD patients,
      rank-ordered for disease severity from minimal chorea to generalized dystonia,
      selected because they were ambulatory despite 3 to 17 years' disease duration.
      One patient was from a nursing home (walked with assistance) and five were living
      independently, either alone or with a working spouse who was the caregiver. MAIN
      OUTCOME MEASURES: Standardized gait evaluations (retroreflective markers on
      standard bony landmarks) from five video angles, fed into digitizer to computer
      generate joint angles and standard gait kinematic parameters. RESULTS: Wide
      variability in gait kinematic parameters and joint interaction plots (phase plane
      and angle-angle plots) was observed between individuals and successive trials of
      the same limb, tending to increase with disease severity. Joint interaction plots
      show that random, highly variable distractions from planned trajectories are more
      apparent distally. CONCLUSIONS: Chorea in HD does not appreciably affect the
      center of gravity during ambulation, and the consistency of gait profiles at heel
      strike shows that the ultimate target is achieved in each step despite random and
      frequent variability during the gait cycle.

PMID- 9915374
TI  - Slowness to develop force contributes to weakness after stroke.
AB  - OBJECTIVE: To examine weakness after stroke, in terms of both level and rate of
      torque generation. DESIGN: Descriptive. T tests for dependent and independent
      samples and Pearson's product moment correlation coefficients were performed.
      SETTING: A rehabilitation unit. PARTICIPANTS: Ten stroke subjects, aged 56 to 81
      years, undergoing rehabilitation. Ten neurologically normal subjects aged 55 to
      78 years were the controls. OUTCOME MEASURES: Peak isometric elbow flexor and
      extensor torque and time to 90% peak elbow flexor and extensor torque at 6 weeks
      and at 25 weeks after stroke. RESULTS: At 6 weeks after stroke, subjects were
      only half as strong and took two to three times longer to produce torque compared
      to controls (p < or = .05). By 25 weeks after stroke, significant improvements in
      peak torque (p < or = .02) and time to 90% peak flexor torque (p < or = .05) were
      seen so that values were within normal limits. CONCLUSION: Decreased rate of
      torque development compounds the problem of reduced peak torque, which may have
      significant implications for stroke patients, especially in situations where
      muscles are very weak or where force needs to be generated quickly.

PMID- 9915375
TI  - Eye patching in unilateral spatial neglect: efficacy of two methods.
AB  - OBJECTIVES: To determine whether patches obscuring half the visual field affect
      eye movement in subjects with unilateral spatial neglect and whether there is
      consequent improvement in the subject's everyday life, and to interpret the
      potential changes observed with the aid of a theoretical model. DESIGN:
      Prospective and randomized study. SETTING: Rehabilitation medicine department in
      an urban general hospital. PATIENTS: Twenty-two subjects with left unilateral
      neglect. INTERVENTION: Two eye-patching procedures-right half-field patches (n =
      7) and right mononuclar patch (n = 7)-and control group (n = 8). MAIN OUTCOME
      MEASURES: Functional tests (FIM) and analytical tests (measurement of right eye
      movements by photo-oculography) at admission and after 3 months. RESULTS: Results
      of the paired comparison tests showed (1) significant differences between the
      control group and the group with the half-eye patches for total FIM score (p =
      .01) and the displacements of the right eye in the left field (p = .02), and (2)
      no significant differences between the control group and the group with the right
      monocular patch. CONCLUSION: Patching the right half-field helped subjects
      initially regain voluntary control over the deficit. The actual interpretation is
      based on physiologic and psychophysiologic models.

PMID- 9915376
TI  - Cognitive and affective improvement in brain dysfunctional patients who achieve
      inpatient rehabilitation goals.
AB  - OBJECTIVE: To evaluate whether improvements in specific cognitive and affective
      functions are associated with achieving inpatient rehabilitation goals after the
      acute onset of brain dysfunction. DESIGN: Retrospective analysis of data obtained
      in a prospective inception cohort study. STUDY SETTING: Medical center and
      neurological institute. SUBJECTS: Ninety-five heterogeneous brain dysfunctional
      patients who participated in an interdisciplinary inpatient neurorehabilitation
      program. Subjects were classified as having achieved their rehabilitation goals
      (Group 1) or not (Group 2) at time of discharge. MAIN OUTCOME MEASURE: Number of
      treatment goals attained. RESULTS: Although overall level of performance on the
      BNI Screen (BNIS) for Higher Cerebral Functions distinguished patients who later
      achieved their inpatient rehabilitation goals, on admission only performance on
      the visual spatial subtest was associated with later goal attainment. In
      contrast, at discharge, patients who showed greater improvement in awareness,
      affect, visual spatial skills, memory, and attention/concentration were likely to
      obtain their rehabilitation goals. This was true when the initial level of
      performance was taken into account. CONCLUSIONS: Measurement of overall
      neuropsychological status and specific visual spatial abilities at time of
      admission may help determine which brain dysfunctional patients will obtain
      inpatient rehabilitation goals. Improvement in a variety of cognitive and
      affective functions was associated with goal attainment. Early cognitive
      rehabilitation should focus on both cognitive and affective disturbances to
      facilitate recovery and rehabilitation outcome.

PMID- 9915377
TI  - Etiology and incidence of rehospitalization after traumatic brain injury: a
      multicenter analysis.
AB  - OBJECTIVE: To investigate incidence and etiology of rehospitalizations at 1, 2,
      and 3 years after traumatic brain injury. DESIGN: Descriptive statistics were
      computed in a prospective study of etiology and incidence of rehospitalization at
      years 1, 2, and 3 postinjury. Analysis of variance (ANOVA) and chi2 were used to
      identify factors relating to rehospitalization; factors included length of stay,
      admission and discharge functional status, payer source, medical complications,
      injury severity, and demographics. SETTING: Four medical centers in the federally
      sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of
      care includes emergency medical services, intensive and acute medical care,
      inpatient rehabilitation, and a spectrum of community rehabilitation services.
      PARTICIPANTS: Six hundred sixty-five rehabilitation patients admitted to acute
      care within 24 hours of traumatic brain injury between 1989 and 1996. MAIN
      OUTCOME MEASURES: Annual incidence and etiology of rehospitalization. RESULTS:
      The annual incidence of rehospitalization ranged from 20% to 22.5%. Approximately
      half the rehospitalizations were for elective reasons. The most common reason for
      rehospitalization was for orthopedic or reconstructive surgery, followed by
      infectious disorders and general health maintenance. After the first year, the
      incidence of readmissions for seizures and psychiatric difficulties increased
      substantially. ANOVA and chi2 analyses were performed on data from the first year
      postinjury. No statistically significant associations were noted between
      incidence and etiology of rehospitalization and: demographics; injury severity;
      payer source for rehabilitation; concurrent injuries; acute care and
      rehabilitation length of stays; discharge Functional Assessment Measure; and
      discharge residence (p > .05). CONCLUSIONS: There is a relatively stable but high
      rate of rehospitalization for at least 3 years after injury. The costs of
      rehospitalization should be considered when evaluating the long-term consequences
      of injury.

PMID- 9915378
TI  - Predictive validity of the pain and impairment relationship scale in a chronic
      nonmalignant pain population.
AB  - OBJECTIVE: To examine the predictive and incremental validity of the Pain and
      Impairment Relationship Scale (PAIRS) and to determine its ability to measure
      changes in pain beliefs following interdisciplinary treatment. DESIGN: A before
      after treatment design. SETTING: A comprehensive interdisciplinary pain center at
      a large midwest university medical center. INTERVENTIONS: A cognitive-behavioral
      approach to pain management. The day-long program lasted 5 days a week for 4
      weeks. Interventions were designed to improve physical functioning, reduce use of
      health care, and improve pain coping. MAIN OUTCOME MEASURES: Six-month follow-up
      outcome measures included interference with daily activity, pain severity, and
      life control as measured by the Multidimensional Pain Inventory, medication use
      measured by the Medication Quantification Scale, depression measured by the Beck
      Depression Inventory, and the number of health care visits and pain-related
      hospitalizations. RESULTS: Pretreatment PAIRS scores correlated significantly
      with interference with daily activities, pain severity, life control, health care
      visits, and depression. Stronger correlations were obtained between posttreatment
      PAIRS scores and all follow-up outcome measures. Posttreatment PAIRS scores
      accounted for a significant portion of the variance beyond that in demographic
      variables and pretreatment PAIRS scores in all but one of the follow-up measures.
      PAIRS scores changed significantly (p < .0001 ) in a positive direction after
      treatment. CONCLUSIONS: The PAIRS has excellent predictive validity, and can be
      used effectively to monitor individual and programmatic changes.

PMID- 9915379
TI  - Trunk proprioception: enhancement through lumbar bracing.
AB  - OBJECTIVES: To examine the effects of a neoprene lumbar brace on the
      proprioceptive ability of subjects without pathology and to determine whether
      those with poorer proprioception were more affected by the brace. STUDY DESIGN:
      Randomized 2 x 2 Latin square cross-over design. SETTING: Laboratory in an
      educational institution. SUBJECTS: Forty asymptomatic subjects matched by gender,
      age, weight, and height. METHOD: Blindfolded subjects performed a position
      matching task in which they flexed the trunk in the sagittal plane. Six positions
      across the range of motion were examined. Angular data were recorded by a lumbar
      motion monitor secured by straps to the subject's trunk. MAIN OUTCOME MEASURE:
      Absolute, constant, and variable errors in braced and unbraced conditions.
      RESULTS: The mean absolute, constant, and variable errors were 3.6 degrees, .45
      degrees, and 4.4 degrees, respectively. Absolute, constant, and variable errors
      were significantly decreased when wearing a brace. However, the magnitude of the
      decreases were small (<1.0 degrees) for all errors when wearing a brace. The high
      error group's absolute error improved significantly (p < .05), from 6.0 degrees
      when unbraced to 4.0 degrees when braced. In contrast, absolute error
      measurements for subjects in the low error group were unchanged, with an error of
      2.0 degrees when unbraced and 2.3 degrees when braced. CONCLUSIONS: The findings
      suggest that a neoprene lumbar brace improves the somatosensory information
      received by the central nervous system and results in less error in trunk
      positioning. Persons with less ability to match trunk position will benefit more
      from wearing a neoprene brace than will those who are already adept at the task.

PMID- 9915380
TI  - Inspiratory muscle training protocol using a pressure threshold device: effect on
      dyspnea in chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the ability of patients with chronic obstructive pulmonary
      disease (COPD) to accomplish 6 weeks of inspiratory muscle training (IMT) using a
      pressure threshold device, and to observe how the training affected inspiratory
      muscle strength and dyspnea. DESIGN: Pilot study comparing baseline values with
      posttest values. SUBJECTS: Four adults with severe COPD (the mean of the forced
      expiratory volume in 1 second [FEV1] was 28% of predicted value). METHODS: Daily
      IMT sessions of 5 to 30 minutes' duration and weekly training load increments of 
      2 to -4cmH2O over a 6-week period with the training device at loads of >30% of
      baseline maximal inspiratory pressure (PImax). OUTCOME MEASURES: Dyspnea measures
      were Mahler's Baseline and Transition Dyspnea Index and the Borg category-ratio
      scale administered during a submaximal exercise protocol. RESULTS: All subjects
      tolerated the training load, improved their inspiratory muscle strength, and
      reported reduced dyspnea. CONCLUSION: Using a constant-load pressure threshold
      device to attain loads of >30% of the patient's baseline PImax is a feasible way
      to accomplish inspiratory muscle training in adults with severe COPD.

PMID- 9915382
TI  - Stroke patients: do they have a predilection for extrapyramidal side effects from
      amiodarone?
AB  - This report describes two patients with recent stroke who, upon transfer to the
      rehabilitation medicine service, were noted to have extrapyramidal features. Both
      patients were receiving amiodarone for management of atrial fibrillation. When
      this medication was discontinued, there was slow resolution of extrapyramidal
      features and an improvement in function. Physicians managing acute stroke
      patients should be alert for features of amiodarone neurotoxicity, because these
      side effects may occur more readily in patients with recent neurologic impairment
      and may impede their progress in rehabilitation.

PMID- 9915381
TI  - The long-term effects of pulmonary rehabilitation in patients with asthma and
      chronic obstructive pulmonary disease: a research synthesis.
AB  - OBJECTIVE: To present a critical review and meta-analysis of studies evaluating
      the long-term effects of pulmonary rehabilitation in patients with asthma and
      chronic obstructive pulmonary disease (COPD). DATA SOURCES: A database of
      articles published over the last 45 years, compiled by using medical subject
      heading key words pulmonary, obstructive, rehabilitation, and exercise. Articles
      not written in English, Dutch, or German and abstracts were excluded. STUDY
      SELECTION: Selected studies (1) evaluated the effects of pulmonary
      rehabilitation, (2) included patients with asthma or COPD older than 18 years,
      (3) evaluated outcome measures of exercise capacity or health related quality of
      life (HRQL), and (4) included a control condition lacking exercise training. DATA
      EXTRACTION: Independent extraction by two reviewers. DATA SYNTHESIS: For each
      outcome, summary effects were computed by pooling standardized mean differences
      as well as raw mean differences. Significant improvements were found for all
      outcomes (p < .001). Sensitivity analyses for methodological quality of the
      selected studies did not change summary effect sizes. Effect sizes were
      significantly heterogeneous for the outcome endurance time (p < .0001). Pooling
      raw mean differences revealed overall effects in 6-minute walking distance (49+/
      26 m) and all 4 dimensions of the chronic respiratory questionnaire (range, 0.5+/
      0.3 to 0.8+/-0.3 points), indicating substantial improvements in these outcomes.
      Significant summary effect sizes were found up to 9 months after finishing
      rehabilitation for maximal exercise capacity (p < .003) and 6-minute walking
      distance (p < .005). CONCLUSIONS: Patients with asthma and COPD benefit from
      pulmonary rehabilitation.

PMID- 9915383
TI  - Pectoralis major rupture during gait training: case report.
AB  - Rupture of the pectoralis major muscle is rare. The majority of cases have been
      reported in young, healthy athletes during strenuous activities such as weight
      lifting, wind surfing, and football. The injury is thought to result from either
      a forceful contraction of the muscle applied to an immovable object or a sudden
      stretching force applied to the contracting muscle. This report describes a case
      of a 79-year-old man with a history of severe degenerative joint disease of the
      right hip and a recent left transtibial amputation secondary to a failed arterial
      bypass procedure. During prosthetic training the patient developed acute pain in
      the left shoulder and left axilla, which prevented him from further ambulation.
      Physical examination was consistent with a partial rupture of the pectoralis
      major. The causative factors of pectoralis major rupture in this patient are
      reviewed. To our knowledge, this is the first such case reported.

PMID- 9915384
TI  - Nonselective debridement and antimicrobial cleansing of a venting ductal breast
      carcinoma.
AB  - A woman with a moderately differentiated carcinoma that erupted through the skin
      and amputated her breast was treated with whirlpool, topical antimicrobials,
      radiation, and chemotherapy. The draining, necrotic, and septic wound was treated
      for 5 months with a whirlpool containing dilute povidone-iodine solution and
      intravenous chemotherapy. Wet bandages, necrotic tissue, and softened eschar were
      removed by whirlpool agitation or mechanically debrided. To start treatment the
      wound was dressed with Debrisan crystals and sterile gauze for 1 week.
      Afterwards, wet-to-dry dressings wetted with Dakin's solution were applied.
      Tissue ingrowth at the wound margin started after 2 weeks, with whirlpool
      treatments effecting a tissue-reddening hyperemia. Wound drainage ceased after 2
      months, with granulation and revascularization resulting. Eleven months later the
      wound was closed, aseptic, and undergoing dry flaking. The patient was cancer
      free with a completely healed wound 2 years after treatment. In this case,
      nonspecific debridement using whirlpool and topical antimicrobials promoted
      healing of an open fungating wound from a breast carcinoma.

PMID- 9915385
TI  - Measuring first ray mobility with a new device.
AB  - First ray hypermobility has been linked to many abnormal conditions in the foot.
      First metatarsal vertical displacement is proportional to the measurement of
      first ray dorsiflexion. A new device that measures first ray mobility has been
      built and tested. The device applies a dorsiflexing force to the head of the
      first metatarsal and measures the amount of vertical displacement that results.
      The design and instrumentation of the device is described. A safe and reliable
      testing procedure for measuring maximal first ray displacement is discussed.
      Clinicians could use this measure when selecting treatment options for patients
      who suffer foot pathologies resulting from faulty mechanics of the first ray.

PMID- 9915386
TI  - Spontaneous spinal epidural hematoma.

PMID- 9915387
TI  - Discharge destination in stroke.

PMID- 9915388
TI  - Use of a mandibular fracture score to predict the development of complications.
AB  - PURPOSE: Mandibular fractures are common facial injuries. Classifications are
      diverse and sometimes correlated with specific treatment modalities.
      Osteosynthesis using plate and screws is the standard method of fracture
      treatment. To evaluate the outcome of such fracture management in our clinic, we
      developed a numeric scoring system for mandibular fractures and investigated the
      relationship between the scoring of the fracture being treated and the incidence
      of complications after surgical treatment. PATIENTS AND METHODS: Seventy-six
      adult patients treated over a 2-year period were evaluated, and the fractures
      were classified using the mandibular trauma score. This score was based on
      clinical and radiologic evaluation of each fracture line and ranks from 0 to 15
      points. Osteosynthesis was performed using the AO plate systems. Patients were
      followed-up postoperatively for the presence of complications. RESULTS: During
      the 2-year period, 76 patients with 134 fractures underwent plate osteosynthesis.
      Fracture scoring indicated a homogeneous distribution between uncomplicated and
      severe fractures. The incidence of complications increased with the fracture
      severity, assessed by the fracture score index. Severe fractures showed fewer
      complications when treated with a rigid plate system, whereas low-score fractures
      showed better results when treated with less rigid systems. CONCLUSIONS: The
      numeric scoring system for mandibular fractures allows an objective and
      standardized assessment of the degree of severity of a fracture and may
      facilitate decisions about the use of specific treatment modalities.

PMID- 9915389
TI  - Six year's experience with the zygomatic "sandwich" osteotomy for correction of
      malar deficiency.
AB  - PURPOSE: This study discusses the rationale, modifications, and complications of
      an osteotomy technique used to increase malar projection. PATIENTS AND METHODS:
      Seventy "sandwich" zygomatic osteotomies were performed in a 6-year period.
      Hydroxyapatite (HA) blocks were used to stabilize the anterolateral rotation of
      the zygomatic body in 44 osteotomies, calcium carbonate blocks were used in 23,
      calvarial bone grafts in three, a piece of bovine cartilage in one, and a bone
      graft from a chin ostectomy procedure combined with mesh osteosynthesis in one
      procedure. Fifty-six zygomatic osteotomies were combined with Le Fort I-type
      osteotomies (eight with a midline split). Nineteen zygomatic osteotomies were
      performed simultaneously with a Le Fort I-type osteotomy and a rhinoplasty with
      lateral osteotomies. RESULTS: The increase of malar projection and the stability
      of the procedure could not be measured on conventional three-plane cephalograms.
      However, patient's and surgeon's satisfaction were high and remained so during
      the follow-up period (maximum, 6.5 years; minimum, 6 months). Three patients
      developed maxillary sinusitis. In two of them, this was clearly related to
      fragmentation of an HA block. A Treacher-Collins patient developed a chronic
      fistula in the upper vestibule, caused by leakage of infraorbitally placed HA
      granules. In two cases, a fracture of the zygomatic arch occurred. Osteosynthesis
      was performed in one of them. CONCLUSION: With proper technique and care not to
      fracture the interpositional HA block, complications are rare. The procedure is
      expedient and provides predictable and stable correction of malar deficiency.

PMID- 9915390
TI  - A prospective evaluation of the value of preoperative laboratory testing for
      office anesthesia and sedation.
AB  - PURPOSE: The purpose of this investigation was to determine whether routine
      laboratory testing affected the clinician's preoperative evaluation and decision
      making process for patients undergoing general anesthesia or intravenous sedation
      in the oral and maxillofacial surgery office. PATIENTS AND METHODS: This was a
      prospective evaluation of the records of 458 who required an office general
      anesthetic or intravenous sedation for routine dentoalveolar surgery. The
      patients ranged in age from 15 to 54 years and were categorized as American
      Society of Anesthesiologists Classification I or II. Fifty-two percent were
      female. All patients underwent a history and physical examination, complete blood
      cell count, and urine analysis. Female patients were tested for pregnancy by
      measuring the serum beta human chorionic gonadotropin level. All patients older
      than 40 years of age were further evaluated by posterior-anterior and lateral
      chest radiographs, as well as electrocardiography. On the day of surgery, the
      data were reviewed and analyzed, and specific components of the history were
      reassessed. The results of the decision-making process were evaluated by one
      investigator. RESULTS: From the 458 patients initially enrolled, 78 failed to
      return on the appointed day. Of the 235 patients requiring general anesthesia who
      did return on the appointed day, five had aberrant laboratory values (2%). These
      consisted of one patient with a low hematocrit, one with a low red blood cell
      count, one with a low white blood cell count, and two with a urine analysis
      positive for blood. No procedure was canceled based on the aberrant data. Of the
      145 patients requiring intravenous sedation who did return on the appointed day,
      six had aberrant laboratory values (4%). Two patients exhibited elevated white
      blood cell counts, two possessed low red blood cell counts, one known to have
      diabetes had an elevated urine glucose, and one patient with an elevated human
      chorionic gonadotropin level realized that her menstrual cycle was delayed. The
      latter two patients had their procedures deferred. CONCLUSIONS: Based on the
      results of this study, a good history and physical examination and then
      reassessment of key portions of the history were the major factors in the
      development of the anesthetic treatment plan. Laboratory data had little if any
      effect on the decision-making process.

PMID- 9915391
TI  - Long-term changes in clinical signs and symptoms and disc position and morphology
      in patients with nonreducing disc displacement in the temporomandibular joint.
AB  - PURPOSE: The purpose of this study was to examine disc position and
      configuration, as well as clinical findings, during the natural course of
      nonreducing disc displacement of the temporomandibular joint (TMJ). PATIENTS AND
      METHODS: The subjects were 21 patients (24 affected joints) for whom a diagnosis
      of anterior disc displacement without reduction in the TMJ had been made on
      arthrography, but who had received no treatment for more than 12 months. The disc
      position and configuration were examined at a mean follow-up of 27.1 months using
      magnetic resonance imaging. Clinical signs and symptoms were also examined. As a
      control, 30 joints in 15 persons who had no current or previous TMJ symptoms were
      studied. RESULTS: The patients' clinical signs and symptoms tended to be
      alleviated during the follow-up period. In all patients, the disc was displaced
      anteriorly on mouth closure, and it did not reduce into normal position during
      mouth opening at the follow-up, whereas normal disc position was found in all of
      the controls. In the patients, the disc deviated from the normal biconcave
      configuration found in all of the controls, frequently showing enlargement of the
      posterior band, even thickness, folding, and convex configurations in the follow
      up magnetic resonance imaging. CONCLUSION: Disc displacement does not resolve,
      and continued disc deformity is common in the natural course of nonreducing disc
      displacement of the TMJ, although the clinical signs and symptoms tend to become
      alleviated.

PMID- 9915392
TI  - Condylar position with rigid fixation versus wire osteosynthesis of a sagittal
      split advancement.
AB  - PURPOSE: In this randomized clinical study, two groups of patients who underwent
      a bilateral sagittal split osteotomy and either wire osteosynthesis or rigid
      fixation were compared. PATIENTS AND METHODS: Cephalometric radiographs obtained
      before surgery, immediately after surgery, and at 8 weeks, 6 months, and 1 and 2
      years after surgery were available for 125 of these patients, 63 with wire
      fixation and 62 with rigid fixation. All were traced by an independent examiner,
      and vertical and horizontal changes in condylar position were recorded for each
      period. RESULTS: Condylar movement was slightly different with the two fixation
      techniques beyond 8 weeks postsurgery, but the ultimate position of the condyle
      was not different. The condyles in both groups moved posterior and superior.
      There initially was a correlation between the amount of advancement and the
      amount the condyle moved inferior in both groups, but this diminished with time.
      In addition, there was a weak but significant positive relationship between
      forward rotation of the proximal segment and superior condylar position
      immediately after surgery, which did not exist at later periods. CONCLUSIONS:
      Whether wire osteosynthesis or rigid fixation was used, the ultimate condylar
      position was posterior and superior after a bilateral sagittal split osteotomy to
      advance the mandible. No single factor could be identified to account for this
      change. It is suggested that change in mechanical load may have resulted in
      remodeling and adaptation of the condyles.

PMID- 9915393
TI  - Endoscope-assisted fixation of mandibular condylar process fractures.
AB  - PURPOSE: Reduction and plate osteosynthesis of condylar fractures often require a
      wide extraoral approach with the risk of aesthetic impairment and possible facial
      nerve palsy. To avoid complications, the purpose of this pilot study was to use
      an endoscopic device for the treatment of condylar fractures also allowing for
      endoscopically assisted plate application. PATIENTS AND METHODS: Seven condylar
      fractures were operated under endoscopic control. In three patients, a newly
      developed device for endoscopically controlled plate application was clinically
      tested. The new device and the application technique is described in detail.
      RESULTS: In two of three cases using this approach, fracture healing was achieved
      with the condyle in the anatomically correct position. In the third case the
      plate had to be removed early because of insufficient screw fixation. CONCLUSION:
      This technique may be helpful to further minimize surgical trauma in head and
      neck fracture treatment. The newly developed plate application device may also be
      used to approach other regions of the skull eg, the skull base, the zygoma, or
      the orbit.

PMID- 9915394
TI  - Ultrasonographic criteria for diagnosis of cervical lymph node metastasis of
      squamous cell carcinoma in the oral and maxillofacial region.
AB  - PURPOSE: This retrospective study was done to establish an objective criterion
      for sonographic diagnosis of cervical lymph node metastasis of squamous cell
      carcinoma in the oral and maxillofacial region. PATIENTS AND METHODS: A
      quantitative criterion for differentiating metastatic from nonmetastatic nodes
      was statistically calculated using logistic regression analysis of 106 cervical
      lymph nodes in 41 patients. A prospective study was then conducted to ascertain
      the reliability of the criterion for 82 nodes in another 23 patients. RESULTS:
      The following equation was obtained from the retrospective study: Y = 1/(1+e(
      lambda) (lambda = -7.5709 + 4.2423 X1 + 1.9354 X2 + 0.5507 X3) Y represents the
      predicted value; lambda, also representing a predicted value, was defined as
      negative for nonmetastatic and positive for metastatic nodes; X1, signifying the
      existence of an echogenic hilus, was defined as 0 for presence and 1 for absence;
      X2, signifying the internal echo pattern, was defined as 0 for homogeneous and 1
      for heterogeneous; X3, signifying the minimal diameter, was the actual measured
      value (mm). This equation showed a sensitivity of 82%, a specificity of 91%, and
      an accuracy of 88% in the prospective study. CONCLUSION: The equation calculated
      by logistic regression analysis was a reliable criterion for diagnosing cervical
      lymph node metastasis.

PMID- 9915395
TI  - The effect of chitosan (poly-N-acetyl glucosamine) on lingual hemostasis in
      heparinized rabbits.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of chitosan on
      lingual hemostasis in rabbits whose coagulation pathway had been impaired by
      administration of intravenous heparin. MATERIALS AND METHODS: Bleeding times were
      measured for bilateral (15 mm x 2 mm) tongue incisions in 10 New Zealand white
      rabbits. Using a randomized, blinded experimental design, one incision in each
      animal was treated with chitosan, and the other was treated with the control
      vehicle without chitosan. Activated coagulation times and extraoral bleeding
      times were measured for each animal before, during, and after heparinization.
      RESULTS: Intravenous infusion of heparin more than tripled the mean activated
      coagulation time and increased mean systemic bleeding time by 40%. In this
      heparinized animal model, lingual incisions receiving the experimental substance
      showed a 43% improvement in bleeding time as compared with lingual incisions
      receiving the control solution (P< or =.001). Chitosan treatment brought bleeding
      time of the lingual incision for heparinized animals within the normal range.
      Scanning electron microscopic evaluation of the incisions treated with chitosan
      showed an altered red blood cell morphology and an unusual affinity between
      erythrocytes. CONCLUSIONS: Topical application of chitosan to lingual incisions
      effectively decreased intraoral bleeding time in a therapeutically anticoagulated
      (heparinized) rabbit model. Chitosan facilitated lingual hemostasis, possibly
      through interaction with erythrocytes, linking them together to establish a
      cellular clot or hemostatic plug.

PMID- 9915396
TI  - Bimaxillary surgery using an intermediate splint to position the maxilla.

PMID- 9915397
TI  - Bimaxillary surgery without the use of an intermediate splint to position the
      maxilla.

PMID- 9915398
TI  - Slow-growing midline submental mass.

PMID- 9915399
TI  - Carcinoma of the tongue in two siblings.

PMID- 9915400
TI  - Stress fracture of the tibia: an unusual complication of reconstructive surgery
      of the mandible.

PMID- 9915401
TI  - Anomalous relationship of the facial nerve and the retromandibular vein: a case
      report.

PMID- 9915402
TI  - Anesthesia of the inferior alveolar and lingual nerves as a complication of a
      fractured condylar process.

PMID- 9915403
TI  - Cystic echinococcosis of the parapharyngeal space: case report with a 20-year
      follow-up.

PMID- 9915404
TI  - Localized hypertrophic neuropathy involving the inferior alveolar nerve.

PMID- 9915405
TI  - Unilateral trismus in a patient with trigeminal neuralgia due to microvascular
      compression of the trigeminal motor root.

PMID- 9915406
TI  - Practicing a protected scope of oral and maxillofacial surgery.

PMID- 9915407
TI  - Practicing a protected scope of oral and maxillofacial surgery.

PMID- 9915408
TI  - Renal cell carcinoma: management of advanced disease.
AB  - PURPOSE: We provide a current review of the management of advanced renal cell
      carcinoma. MATERIALS AND METHODS: A comprehensive literature review of peer
      reviewed articles which address the current management of metastatic renal cell
      carcinoma was performed. RESULTS: Renal cell carcinoma is the seventh leading
      cause of cancer, accounting for 3% of malignancies in men. The incidence of renal
      cell carcinoma has increased significantly by 38% from 1974 through 1990 at least
      in part related to earlier diagnosis with the common use of new radiological
      techniques. Cytotoxic chemotherapy remains poor as a treatment alternative.
      Interferon-alpha produces responses in 15 to 20% of patients but clinical
      usefulness as monotherapy has been surpassed by interleukin-2 (IL-2). IL-2 is the
      first immunotherapy to produce durable remissions resulting in approval by the
      Food and Drug Administration. Although high dose bolus IL-2 schedules have the
      longest followup, IL-2 administered on other schedules may have enhanced
      efficacy. Randomized trials are attempting to delineate the appropriate role for
      various doses and schedules. CONCLUSIONS: Advanced renal cell carcinoma, once a
      disease relegated to the incurable, during the last decade has evolved into a
      malignancy that may be associated with cure. The first evidence of this potential
      is the clear and unequivocal demonstration that IL-2 produces durable complete
      remissions. Building upon this immunotherapeutic approach the future treatment of
      renal cell carcinoma will incorporate new immunological technology, including
      gene, dendritic cell, vaccine and antibody therapy.

PMID- 9915409
TI  - Comparison of screening methods in the detection of bladder cancer.
AB  - PURPOSE: We prospectively evaluate and compare the sensitivity and specificity of
      urine cytology, BTA stat, NMP22, fibrin/fibrinogen degradation products (FDP),
      telomerase, chemiluminescent hemoglobin and hemoglobin dipstick to detect bladder
      cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 57
      patients with bladder cancer, and 139 without evidence of bladder malignancy on
      cystoscopy or a negative biopsy of indeterminate lesions. A cytology report was
      available for 125 patients and interpreted independently. BTA stat, NMP22 and FDP
      were analyzed according to manufacturer specifications. The telomerase assay was
      performed on cells collected from urine by centrifugation in preparation for
      polymerase chain reaction based amplification using the telomeric repeat
      amplification protocol assay. The chemiluminescent screening assay for hemoglobin
      in urine uses the pseudoperoxidase activity of hemoglobin on hydrogen peroxide
      and subsequent oxidation of 7-dimethylaminonaphthalene-1,2-dicarbonic acid
      hydrazide to generate chemiluminescence emission. Hemoglobin dipstick was
      interpreted as positive if the hemoglobin content in the urine was trace or
      greater. RESULTS: Overall sensitivity with urine cytology, BTA stat, NMP22, FDP,
      telomerase, chemiluminescent hemoglobin and the hemoglobin dipstick was 44, 74,
      53, 52, 70, 67 and 47%, respectively. Specificity with cytology, telomerase and
      FDP was high (95, 99 and 91%, respectively) but BTA stat, NMP22 (optimized),
      chemiluminescent hemoglobin (optimized) and the hemoglobin dipstick demonstrated
      lower specificity of 73, 60, 63 and 84%, respectively. Stepwise logistic
      regression analysis revealed that for all tumors, and within each tumor grade and
      stage telomerase had the strongest association with bladder cancer among all
      tests (69% overall concordance). Telomerase was also positive in 91% of the
      patients (10 of 11) with carcinoma in situ. CONCLUSIONS: Urinary telomerase had
      the highest combination of sensitivity and specificity (70 and 99%, respectively)
      for bladder cancer screening in these patients. It was the strongest predictor
      with superior accuracy in patients with grade 1 and noninvasive tumors (pTa), and
      extremely useful in patients with carcinoma in situ. Telomerase appears to be
      promising and outperformed cytology, BTA stat, NMP22, FDP, chemiluminescent
      hemoglobin and hemoglobin dipstick in the prediction of bladder cancer.

PMID- 9915410
TI  - Management of hereditary pheochromocytoma in von Hippel-Lindau kindreds with
      partial adrenalectomy.
AB  - PURPOSE: In patients with von Hippel-Lindau disease multiple bilateral adrenal
      pheochromocytoma can develop, which has traditionally been treated with
      adrenalectomy. Partial adrenalectomy can preserve normal adrenal function and
      avoid the morbidity associated with medical adrenal replacement. We demonstrate
      whether adrenal function could be preserved by partial adrenalectomy in patients
      with von Hippel-Lindau disease. MATERIALS AND METHODS: From 1995 to 1998, 13
      consecutive von Hippel-Lindau disease patients with pheochromocytoma underwent 14
      partial and 6 complete unilateral adrenalectomies. Function of residual normal
      adrenal and recurrence of adrenal pheochromocytoma were determined at followup.
      RESULTS: Of the patients 2 had undergone unilateral adrenalectomy and 1 had
      undergone complete and partial adrenalectomy previously. Following surgery
      residual normal adrenal tissue consisted of 1 partial adrenal in 3 patients,
      bilateral partial adrenal in 5, partial and complete adrenal gland in 1, 1
      complete adrenal gland in 3 and no adrenal tissue in 1. Three patients with
      residual adrenal tissue were placed on medical adrenal replacement until
      adrenocorticotropic hormone stimulation testing demonstrated adrenocortical
      function. In 2 patients 1 adrenal and 2 extra-adrenal new pheochromocytomas
      developed 11 and 152 months, respectively, after partial adrenalectomy. No
      morbidity related to pheochromocytoma was observed during followup. CONCLUSIONS:
      Partial adrenalectomy can preserve adrenal function in patients with a hereditary
      form of pheochromocytoma.

PMID- 9915411
TI  - Relaxation of micro indentations in calcium oxalate urinary stones.
AB  - PURPOSE: We define energy requirements for stone micro indentation as a
      quantifiable event equivalent to in vivo energy delivery and investigate the
      change in indentation characteristics with time. MATERIALS AND METHODS: The 7
      stones extracted from 7 patients were cut, embedded in resin and polished.
      Multiple micro indentations were performed on each stone section using a diamond
      Vickers micro indentor with a 500x light microscope and video system. The
      resulting indentations were observed by optical and scanning electron microscopy
      as a function of time. Organic matrix content was determined by dissolving stones
      in ethylenediaminetetraacetic acid solution. RESULTS: The energy requirement for
      stone indentation varies among stones (median range 43.6 to 109.9 kg/mm2) and at
      different locations in the same stone. Indentations relaxed by 10 to 70% during
      the first 2 weeks after indentation. Stones with a high organic matrix content
      were ductile and the phenomenon of indentation relaxation was pronounced.
      Brittle, low matrix stones relaxed to a lesser extent. CONCLUSIONS: The
      relaxation phenomena may have a practical implementation when considering repeat
      shock wave lithotripsy. A significant fraction of the energy invested in a stone
      which did not cause fracture or critical cracks is lost within 1 to 2 weeks after
      the procedure, particularly in elastic stones with a high organic matrix content.
      We suggest that the preferred interval for repeat shock wave lithotripsy be less
      than 2 weeks.

PMID- 9915412
TI  - Interactive 3-dimensional computerized tomography reconstruction in evaluation of
      the living renal donor.
AB  - PURPOSE: We evaluated the efficacy of helical computerized tomography and a
      software program capable of 3-dimensional (D) reconstruction in assessment of the
      living renal donor. MATERIALS AND METHODS: A total of 20 consecutive patients (40
      renal units) were evaluated using computer software and anatomical findings were
      assessed. Patient time and charges were compared with renal angiography and
      excretory urography (IVP). RESULTS: A total of 25 anomalies were identified in 21
      kidneys using 3-D imaging. Accessory arteries were seen in 13 kidneys. Abnormal
      venous anatomy was found in 7 kidneys, including circumaortic renal veins in 2,
      multiple veins in 4 and a renal vein that drained into the gonadal vein in 1.
      Collecting system anomalies included a bifid pelvis and a duplicate ureter in 1
      case each. Benign cysts were noted in 3 kidneys. Three patients were excluded
      from study due to persistent hypertension, death of the recipient before
      transplantation and bilateral aberrant vasculature, respectively. Intraoperative
      findings of the 17 kidneys removed for transplantation correlated with those
      demonstrated on 3-D reconstruction. Total preoperative imaging charges were
      decreased 50% compared to renal angiography and IVP, and the procedure related
      discomfort and potential morbidity were reduced significantly. Procedure time was
      reduced from 7 hours to 30 minutes with no resultant mandatory time off work or
      periprocedure restrictions in patient diet and/or activity. CONCLUSIONS: The
      enhanced 3-D computerized tomography reformation and reconstruction process
      appears to be as accurate as renal angiography for arterial anatomy, and more
      sensitive than renal angiography and IVP in evaluating venous and parenchymal
      anatomy. This software program provides superior and interactive imaging at
      substantially lower cost with minimal patient time, discomfort and morbidity.

PMID- 9915413
TI  - Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long
      term followup.
AB  - PURPOSE: The true incidence and biological behavior of cystic renal cell
      carcinoma are not known. To our knowledge we present the largest series of
      patients with cystic renal cell carcinoma with long-term followup. MATERIALS AND
      METHODS: We reviewed the Mayo Clinic surgical pathology files of renal cell
      cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily
      chose 75% tumor involvement by cysts as a cutoff for inclusion in the study.
      RESULTS: We identified 24 cases of clear cell renal cell carcinoma with 75% or
      greater involvement by cysts comprising 0.79% of 3,047 renal cell cancer cases
      resected at our institution between 1969 and 1997. Mean patient age was 62.7
      years (range 40 to 83). A total of 11 patients (46%) underwent radical
      nephrectomy, 4 (17%) simple nephrectomy, 3 (12%) partial nephrectomy and 6 (25%)
      tumor enucleation. Mean tumor involvement by cysts was 84% (range 75 to 95) and
      in 11 cases (46%) involvement was 90% or greater. Cancer stage was T1 in 20
      patients (83%), T2 in 1 (4.4%) and T3a in 4 (12.5%). Cancers were diploid in all
      but 1 case. Mean followup was 77.6 months (range 8 to 428, median 51). A total of
      22 patients (92%) had no evidence of cancer and 2 died of intercurrent disease.
      CONCLUSIONS: Our results indicate that cystic renal cell carcinoma is uncommon
      and usually cured by resection, regardless of size, stage or number of cysts.
      These patients may benefit from nephron sparing surgery, such as partial
      nephrectomy.

PMID- 9915414
TI  - Treatment of transplant ureteral stenosis with endoureterotomy.
AB  - PURPOSE: The safety and efficacy of treating renal transplant ureteral stenosis
      with the Acucise endoureterotomy catheter are described. MATERIALS AND METHODS:
      We treated 4 women and 3 men 31 to 63 years old (mean age 45) with Acucise
      endoureterotomy for distal (6) and proximal (1) ureteral stenosis. Diagnosis was
      based on increasing serum creatinine and hydronephrosis on ultrasound, and
      confirmed by antegrade nephrostogram. One patient had recurrence and, therefore,
      8 procedures were performed. Mean followup was 13 months (range 7 to 21).
      RESULTS: Technical success was 100%. One patient had a recurrent stricture and
      was successfully re-treated. Of the patients 3 had chronic rejection and renal
      failure, and 4 had stable renal function. All ureters remain patent to date.
      CONCLUSIONS: Treatment of short ureteral stenosis with Acucise endoureterotomy in
      a renal transplant is safe and effective. Furthermore, it can be performed in an
      ambulatory setting with minimal morbidity. This procedure should be considered as
      the initial approach for distal ureteral stenosis in the transplanted kidney.

PMID- 9915415
TI  - Rectosigmoid urinary diversion: the functional significance of creating an
      intussuscepted colorectal valve.
AB  - PURPOSE: We assess the functional importance of a colorectal valve in patients
      with rectal urinary diversion. MATERIALS AND METHODS: A retrospective evaluation
      of 87 patients with an anal sphincter controlled bladder substitute was
      performed. Of these patients 42 had colorectal valves and 45 did not. Evaluation
      included serum chemistry studies and arterial blood samples to study the impact
      of the colorectal valve on homeostasis. RESULTS: There was a statistically
      significant difference between the 2 groups in pH, carbon dioxide partial
      pressure, bicarbonate, base excess and chloride in favor of patients with a
      colorectal valve. CONCLUSIONS: The difference between the groups was reduction of
      the surface area available for reabsorption when a valve is constructed. This
      finding is of particular importance among patients with a long life expectancy.
      Prophylactic alkalization is necessary in cases without valve reconstruction.

PMID- 9915416
TI  - Decreased sensitivity in the membranous urethra after orthotopic ileal bladder
      substitute.
AB  - PURPOSE: The effect of cystoprostatectomy with orthotopic substitution on
      membranous urethral sensation and subsequent urinary continence is unknown. We
      determined the sensory threshold for electrical stimulation of the membranous
      urethra and correlated it with continence, nerve sparing surgical technique and
      potency. MATERIALS AND METHODS: The sensory threshold was measured in a control
      group of 35 men before radical prostatectomy or cystoprostatectomy and in 47 men
      after cystoprostatectomy and ileal bladder substitution. RESULTS: The sensory
      threshold of the membranous urethra was 9+/-2 in the control group compared to
      27+/-11 mA. in the postoperative group (p<0.001). Patients with daytime
      continence had a threshold of 24+/-9 compared to 39+/-10 mA. in incontinent
      patients (p<0.001). We were unable to show any correlation between the sensory
      threshold in patients with (25+/-10 mA.) and without (31+/-11 mA.) attempted
      nerve sparing surgery (p = 0.1) nor between potent (25+/-12 mA.) and impotent
      (27+/-11 mA.) patients (p = 0.4). CONCLUSIONS: Sensitivity in the membranous
      urethra decreased in patients after cystoprostatectomy and ileal bladder
      substitution. Urethral sensitivity in the sphincter area was better in continent
      than incontinent patients. Since we were unable to find any correlation between
      the sensory threshold and nerve sparing surgery or potency, it may be assumed
      that at least part of the sensory fibers to the membranous urethra pass through
      the pudendal nerve and/or the intrapelvic extrapudendal nerve fibers.

PMID- 9915418
TI  - Complications of the orthotopic intestinal bladder.

PMID- 9915417
TI  - The ileal neobladder: complications and functional results in 363 patients after
      11 years of followup.
AB  - PURPOSE: Since 1986 orthotopic lower urinary tract reconstruction using the ileal
      neobladder has been our diversion of choice in patients of both sexes undergoing
      cystectomy. We report on experience and functional results of the first 363 men
      11 years after this procedure. MATERIALS AND METHODS: Complications were
      assessed, tabulated, subdivided into early (3 months or less postoperatively) and
      late types, and further categorized with respect to relationship to neobladder
      construction. Continence and voiding pattern were individually evaluated via a
      detailed patient questionnaire. RESULTS: Perioperative death occurred in 11
      patients (3%). Neobladder related early and late complications occurred in 56
      (15.4%) and 85 (23.4%) of the 363 patients, respectively. Neobladder related
      early and late abdominal reoperation rates were 0.3 and 4.4%, respectively.
      Perioperative neobladder unrelated early complications were observed in 122
      patients (33.6%) and 44 (12.1%) required operative treatment. Late postoperative
      complications unrelated to the neobladder occurred in 45 patients (12.4%) and 19
      required open surgical revision. Of 290 evaluable patients 96.1% void
      spontaneously, 3.9% perform clean intermittent catheterization in some form and
      1.7% perform regular intermittent catheterization. Daytime and nighttime
      continence was reported as good by 95.9% and satisfactory by 95% of the patients.
      Unacceptable daytime continence requiring more than 1 pad per day occurred in
      only 4.1% of the patients and only 5% are wetting more than 1 pad a night.
      CONCLUSIONS: The ileal neobladder produces good functional results and can be
      constructed with acceptable complications. Our data suggest that although it is
      not a complication-free procedure, we advocate its use when possible.

PMID- 9915419
TI  - A novel technique for management of the en bloc bladder cuff and distal ureter
      during laparoscopic nephroureterectomy.
AB  - PURPOSE: The optimal technique of excising the juxtavesical ureter and bladder
      cuff during laparoscopic nephroureterectomy is still evolving. We report on a
      novel transvesical needlescopic (2 mm. instrumentation) assisted technique of en
      bloc retrieval of the juxtavesical ureter and bladder cuff during laparoscopic
      radical nephroureterectomy for upper tract transitional cell carcinoma. MATERIALS
      AND METHODS: Retroperitoneal laparoscopic nephroureterectomy was performed in 8
      patients using this technique. Two needlescopic ports (2 mm.) inserted
      suprapubically into the bladder were used in combination with a cystoscopically
      positioned Collins knife. RESULTS: Satisfactory circumferential detachment of the
      bladder cuff and en bloc mobilization of 3 to 4 cm. of the intact pelvic
      extravesical ureter were achieved transvesically in each case in a manner
      comparable to open surgery. CONCLUSIONS: This technique simulates established
      open surgical principles of treating the distal ureter during laparoscopic
      nephroureterectomy.

PMID- 9915420
TI  - Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis.
AB  - PURPOSE: Radiation therapy has been used successfully to treat pelvic malignancy
      but morbidity from hemorrhagic cystitis remains a major long-term sequela in 1 to
      2% of patients. Obliterative endarteritis secondary to ionizing radiation leads
      to tissue hypoxia and poor healing. Hyperbaric oxygen therapy has been
      demonstrated to improve angiogenesis and promote healing in radiation injured
      tissue, including the bladder. We describe the treatment and long-term followup
      of a cohort of patients treated with hyperbaric oxygen for hemorrhagic cystitis.
      MATERIALS AND METHODS: A total of 17 patients (mean age 62 years) with
      hemorrhagic cystitis received hyperbaric oxygen following failure of standard
      treatment modalities. Hyperbaric oxygen was administered on a once daily schedule
      (mean number of treatments 14) until hematuria resolved. Followup ranged from 9
      to 60 months (mean 21). RESULTS: Hematuria resolved completely in 11 of 17
      patients (64%), 2 had only residual microscopic hematuria, 2 had improvement but
      died of complications relating to cancer shortly after completion of treatment
      and 2 had recurrence of gross hematuria. Early application of hyperbaric oxygen
      was associated with earlier resolution of hemorrhagic cystitis. CONCLUSIONS:
      Radiation induced hemorrhagic cystitis that does not respond to standard regimens
      can be successfully treated with hyperbaric oxygen. This modality is well
      tolerated even in patients debilitated by advanced cancer and blood loss. Long
      term remission can be achieved in the majority of patients.

PMID- 9915421
TI  - Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line
      derived neurotrophic factor levels in the urine of interstitial cystitis and
      bladder cancer patients.
AB  - PURPOSE: The 2 prominent features of interstitial cystitis are pain and increased
      numbers of mast cells in the bladder. In this pilot study we determined the
      concentration of soluble mediators associated with activation of sensory neurons
      and/or mast cells that were present in the urine. MATERIALS AND METHODS: The
      study groups included 4 interstitial cystitis patients, 7 kidney donors with no
      history of bladder disease as negative controls, 6 bladder cancer patients and 7
      patients with urinary tract infection as reference controls. Urine samples were
      assayed for different soluble mediators using immunoassays for tryptase (a marker
      for mast cell activation), neurotrophic factors (markers of neuronal plasticity)
      and chemokines (markers of inflammatory cell activity). Results were normalized
      based on creatinine concentration. RESULTS: There was a marked increase in the
      average amounts of tryptase and 3 neurotrophic factors in patient urine.
      Interestingly, the mediator profile in the urine of bladder cancer patients was
      indistinguishable from that of interstitial cystitis patients with respect to
      these same 4 proteins. There was no difference between normal control and urinary
      tract infection urine samples. CONCLUSIONS: These findings may account for
      several clinical and pathological features found in interstitial cystitis and
      bladder cancer. Although preliminary due to the limited numbers of patients, they
      also suggest that increased levels of neurotrophin-3, nerve growth factor, glial
      cell line-derived neurotrophic factor and tryptase in the urine could serve as a
      basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.

PMID- 9915422
TI  - Noninvasive detection of bladder cancer with the BTA stat test.
AB  - PURPOSE: We assess the sensitivity and specificity of the noninvasive BTA stat
      urine test for detection of primary and recurrent bladder cancer with special
      reference to the size, grade and stage of the tumors, and examine the effect of
      intravesical bacillus Calmette-Guerin treatment on the results. MATERIALS AND
      METHODS: A total of 250 patients recruited from 3 medical centers provided voided
      urine samples for the BTA stat test and cytopathological study. Of these patients
      162 were monitored following resection of bladder tumors and 88 were evaluated
      for the first time for hematuria or irritative voiding symptoms. Each patient
      underwent cystoscopy. Biopsies were obtained when a bladder tumor was seen or if
      carcinoma in situ was suspected. The sensitivity, specificity and accuracy of the
      BTA stat test were compared to standard voided urine cytology. RESULTS: No tumor
      was found in 122 patients, primary transitional cell carcinoma was found in 71
      and cystoscopy revealed recurrent tumors in 57. Overall sensitivity of the BTA
      stat test was 82.8% and specificity was 68.9%. Sensitivity of urine cytology was
      39.8% and specificity was 95.1%. The BTA stat test detected 90.1% of the primary
      and 73.7% of the recurrent tumors. All patients with carcinoma in situ, high
      grade tumors, muscle invasive cancer and tumors larger than 2 cm. were diagnosed
      by the BTA stat test. CONCLUSIONS: The BTA stat test can be used as a screening
      test for bladder cancer in patients with hematuria or irritative voiding symptoms
      and for surveillance of those who have not been treated with intravesical
      bacillus Calmette-Guerin.

PMID- 9915424
TI  - Pelvic lymph node dissection can be curative in patients with node positive
      bladder cancer.
AB  - PURPOSE: We analyze outcome in a large cohort of patients with bladder cancer
      metastatic to the regional lymph nodes using disease specific survival as the end
      point. MATERIALS AND METHODS: To identify predictors for outcome a large series
      of 193 consecutive patients with regional lymph node metastases operated on from
      1980 to 1990 at Memorial Sloan-Kettering Cancer Center was retrospectively
      analyzed. RESULTS: Among various clinical and pathological parameters, univariate
      and multivariate analyses identified only P (p = 0.0001) and N categories (p =
      0.0006) as parameters predicting disease specific survival. In patients who
      received chemotherapy or irradiation either as part of a nonrandomized clinical
      protocol or on an ad hoc basis no beneficial impact on disease specific survival
      could be demonstrated. Survival was also not affected by pathological grade and
      other histological parameters, since pathological features in patients with node
      positive bladder cancer are uniformly shifted towards high grade lesions with
      vascular or lymphatic invasion and a solid appearance on histological analysis.
      CONCLUSIONS: Nodal metastases carry a poor prognosis despite pelvic
      lymphadenectomy and radical cystectomy. Nevertheless, some node positive cases
      with otherwise localized bladder cancer and/or low N category appear to benefit
      from surgery. Our findings of improved outcome in some individuals with node
      positive disease should be considered in the design of clinical trials evaluating
      the effects of adjuvant or neoadjuvant treatment strategies, and emphasize the
      importance of randomized studies to assess the results of these approaches.

PMID- 9915423
TI  - Do we have a prostate specific antigen for bladder cancer?

PMID- 9915425
TI  - A new technique for correction of the hidden penis in children and adults.
AB  - PURPOSE: A phenomenon known as hidden penis has numerous origins, including
      congenital buried penis and obesity with descent of the escutcheon. No previous
      report to our knowledge mentions abnormal hypermobility of ventral skin and
      dartos fascia, which is a major cause of surgical treatment failures. Because the
      skin and dartos fascia are inadequately attached to Buck's fascia, the corporeal
      bodies telescope proximally inside the scrotum and pubis. Therefore, the
      subdermis of the penoscrotal junction must also be tacked to the tunica albuginea
      ventrally to stabilize the proximal penile skin and prevent the penis from
      retracting into the scrotum. The surgical technique for correction of the hidden
      penis in adult and pediatric patients with adequate penile shaft skin is
      described. MATERIALS AND METHODS: Surgery for hidden penis from multiple causes
      was performed in 6 adults and 7 children. Tacking sutures were taken from the
      subdermis of the ventral penoscrotal junction to the tunica albuginea in all
      cases. A combination procedure with either suprapubic dermatolipectomy, tacking
      of the penopubic subdermis to the rectus fascia, penoscrotal Z plasty,
      circumcision revision or lateral penile shaft Z plasty also was performed in some
      patients. RESULTS: Improvement was noted in all cases. One child requires
      suprapubic lipectomy for optimal improvement and 3 minor wound problems occurred.
      CONCLUSIONS: Surgery for hidden penis achieves marked aesthetic and often
      functional improvement. Surgical failure can be diminished by placing ventral
      tacking sutures from the tunica albuginea to the subdermis of the penoscrotal
      junction.

PMID- 9915426
TI  - Declining sperm counts in the United States? A critical review.
AB  - PURPOSE: Recent reports suggest declining sperm counts in the United States.
      These reports did not include all available data and did not account for
      geographic variations noted in prior studies. We examined all available data on
      U.S. sperm counts and evaluated whether geographic variations account for the
      decline suggested. MATERIALS AND METHODS: We reviewed all 29 U.S. studies from
      1938 to 1996 reporting manually counted semen analyses of 9,612 fertile or
      presumably fertile men. We determined mean sperm concentrations by geographic
      location with weighted analysis of variance, and assessed any changes with time
      by linear regression analysis. RESULTS: Mean sperm concentrations from New York
      were significantly higher than from all other U.S. cities (98.6 versus 71.6 x
      10(6) sperm per cc, respectively, p = 0.006). There has been no statistically
      significant change with time for mean sperm concentrations reported from New York
      (p = 0.49) or from U.S. cities other than New York (p = 0.62). Analysis without
      separating by location revealed a decline (p = 0.047). CONCLUSIONS: Sperm
      concentrations are highest in New York compared to other U.S. cities. When
      accounting for this geographic difference and examining all available data, there
      appears to be no significant change in sperm counts in the U.S. during the last
      60 years. Further studies addressing the causes of geographic variations are
      needed.

PMID- 9915427
TI  - The fate of cryopreserved sperm acquired during vasectomy reversals.
AB  - PURPOSE: Intraoperative sperm banking has been recommended during vasectomy
      reversal. These specimens are maintained as insurance for possible future
      intracytoplasmic sperm injection. We evaluated the fate of specimens collected
      intraoperatively from 48 vasectomy reversal patients. MATERIALS AND METHODS: Of
      75 men 48 (64.0%) agreed to intraoperative sperm banking during vasectomy
      reversal. A total of 135 vials of epididymal sperm, 81 vials of testicular tissue
      and 13 vials of vasal sperm were cryopreserved. RESULTS: Among couples who stored
      sperm 10 (20.8%) voluntarily discarded the specimens within 4 months of vasectomy
      reversal. Specimens from 31 couples (64.5%) remain in storage. Seven couples
      (14.6%) have used frozen sperm for intracytoplasmic sperm injection. In 3 of
      these couples the men were azoospermic after surgery, 2 men had 10,000 to 15,000
      sperm per ml. in the ejaculate with limited motility and 2 had 1 to 2 million
      sperm per ml. with limited motility. The 7 women who underwent intracytoplasmic
      sperm injection ranged between 37 and 39 years old, which was older than the mean
      age of the remaining study group (32.7 years). With intracytoplasmic sperm
      injection fertilization was achieved in all cases and 20 of 47 eggs (42.5%)
      developed into embryos. Of 7 women 4 achieved biochemical pregnancies (57.1%) and
      2 (28.6%) delivered newborns with epididymal sperm. Natural pregnancy occurred in
      7 of 16 vasectomy reversal couples (43.7%) who were followed at least 18 months
      postoperatively but the time to pregnancy averaged 1 year. CONCLUSIONS:
      Cryopreservation of sperm collected at vasectomy reversal is recommended for
      patients undergoing vasoepididymostomy or vasovasostomy. The couples who used the
      cryopreserved sperm for intracytoplasmic sperm injection included husbands whose
      postoperative ejaculate remained azoospermic or severely oligospermic and wives
      who were approaching 40 years old. Only a limited number of couples (14.6% of the
      study group) have used the cryopreserved sperm but the delivered newborn rate
      (28.6%) was comparable to other intracytoplasmic sperm injection data. The
      natural pregnancy rate after vasectomy reversal was 43.7% but the time to
      pregnancy after surgery was lengthy (average 1 year). These findings may be
      helpful for counseling couples who are planning vasectomy reversal surgery and
      may be considering intraoperative sperm banking.

PMID- 9915428
TI  - Rupture of silicone gel filled testicular prosthesis: causes, diagnostic
      modalities and treatment of a rare event.
AB  - PURPOSE: Rupture of the envelope of silicone gel filled testicular prostheses is
      rare and alleged to be unlikely without intraoperative needle puncture. We
      observed that it may be caused by chronic intermittent trauma or a single acute
      increase of pressure, and report diagnostic and therapeutic modalities. MATERIALS
      AND METHODS: Four cases treated by us during the last 10 years are presented. One
      patient had testicular implants for Klinefelter's syndrome, whereas the other 3
      had been treated for female-to-male transsexualism. Diagnosis was confirmed by
      ultrasonography and magnetic resonance imaging. The fibrous capsule surrounding
      the ruptured prosthesis was left intact to allow en bloc surgical extirpation.
      Histological evaluation of the resected specimen was performed. RESULTS: Rupture
      of silicone gel filled testicular implants may be caused by acute or chronic
      pressure without intraoperative needle puncture. CONCLUSIONS: Magnetic resonance
      imaging offers superior diagnostic accuracy and should be regarded the gold
      standard in the evaluation of implant rupture. Ultrasonography is an acceptable
      alternative. In cases when gross symptoms of scrotal inflammation are lacking
      replacement of implants is facilitated by the fibrous capsule that forms around
      any prosthesis. Transcapsular migration of silicone particles was observed even
      when the fibrous capsule was intact.

PMID- 9915429
TI  - Progression detection of stage I nonseminomatous testis cancer on surveillance:
      implications for the followup protocol.
AB  - PURPOSE: To optimize followup in patients with stage I nonseminomatous testis
      cancer on surveillance we evaluated the contribution of each followup modality to
      the detection of progression as well as morbidity and mortality outcomes.
      MATERIALS AND METHODS: After orchiectomy 170 patients with clinical stage I
      nonseminoma were prospectively placed on a surveillance protocol. History,
      physical examination, serum tumor markers, abdominal and pelvic computerized
      tomography (CT), and chest x-ray were used for followup. The number of failures,
      methods and timing of progression detection, treatments required, mortality rate
      and subsequent contralateral primary tumors were recorded. RESULTS: The 170
      surveillance patients were followed a median of 6.3 years. Within 2 years (median
      6.9 months) postoperatively 48 patients (28.2%) had disease progression. History,
      physical examination, markers, CT and chest radiography provided the initial
      evidence of progression in 18 (37.5%), 34 (70.8%), 34 (70.8%), and 4 (8.3%)
      patients, respectively. Each modality was the only indicator of failure in 2
      (4.2%), 4 (8.3%), 10 (20.8%) and 0 cases, respectively. Of the 170 patients 122
      (71.8%) required no additional treatment beyond orchiectomy, 26 (15.3%) received
      1 and 22 (12.9%) underwent more than 1 therapeutic modality. Only 1 patient
      (0.6%) died of disease. Contralateral tumors developed in 5 cases (2.9%)
      therapeutic a mean of 8.1 years after orchiectomy. CONCLUSIONS: In stage I
      nonseminoma patients, surveillance history, physical examination, tumor markers
      and abdominopelvic CT are necessary components of the followup protocol. Removal
      of routine chest x-ray from the protocol would not have changed progression
      detection. The initial surveillance visit must occur by 2 months postoperatively.
      Patients should be followed beyond 5 years and likely for life in addition to
      regular patient self-examination.

PMID- 9915430
TI  - Laparoscopic retroperitoneal lymphadenectomy after chemotherapy for stage IIB
      nonseminomatous testicular carcinoma.
AB  - PURPOSE: We investigated laparoscopic retroperitoneal lymphadenectomy after
      chemotherapy for stage IIB testicular carcinoma in terms of operative
      feasibility, overall morbidity and tumor control. MATERIALS AND METHODS: Between
      February 1995 and April 1998, 24 patients underwent laparoscopic retroperitoneal
      lymphadenectomy following initial chemotherapy for stage IIB (2 to 5 cm.)
      solitary or unilateral lymph node metastases. Mean tumor diameter was 2.4 cm.
      before and 1.1 cm. after chemotherapy. Laparoscopic retroperitoneal
      lymphadenectomy was performed in all patients, including those with complete
      remission. RESULTS: Laparoscopic retroperitoneal lymphadenectomy could be
      completed as planned in all patients and there was no need for conversion to open
      surgery. Operative time was 150 to 300 minutes (mean 240). Blood loss was minimal
      and no blood transfusions were required. The only postoperative complications
      were chylous ascites (5 patients) which resolved with conservative management
      (low fat diet) and a small asymptomatic lymphocele. Histological examination
      revealed necrosis in 71%, mature teratoma in 25% and active tumor in 4% of
      patients. Antegrade ejaculation was preserved in all patients. Mean postoperative
      hospital stay was 4 days, return to normal activities between 1 and 3 weeks, and
      time to complete recovery between 5 and 10 weeks. All patients were well without
      evidence of disease at a mean followup of 24.4 months. CONCLUSIONS: Laparoscopic
      retroperitoneal lymphadenectomy after chemotherapy proved feasible in select
      patients presenting with solitary or unilateral lymph node metastases and was
      associated with a low morbidity. Tumor control was not compromised by the
      laparoscopic approach.

PMID- 9915431
TI  - Electromotive drug administration of lidocaine as an alternative anesthesia for
      transurethral surgery.
AB  - PURPOSE: A multicenter study was undertaken to evaluate the safety, efficacy and
      cost of electromotive drug administration of intravesical lidocaine to produce
      bladder local anesthesia as an alternative to traditional methods of spinal or
      general anesthesia. MATERIALS AND METHODS: A total of 94 patients were enrolled
      in the study who had either a history of bladder tumor that required cold cup
      bladder biopsy with fulguration for possible recurrence as a comparison trial, a
      bladder tumor treated with transurethral resection/fulguration or benign
      prostatic hyperplasia/carcinoma treated with transurethral resection. Pain scores
      using a Verbal Rating Scale were recorded for each individual biopsy, fulguration
      and resection event. Data for direct and indirect costs were collected using a
      standardized form for each patient to capture the details of the procedure,
      including times, drugs and disposables for each patient. RESULTS: There was a
      significant reduction in pain for patients who received electromotive
      intravesical lidocaine compared to no anesthesia for biopsy (p<0.03). Similarly,
      electromotive intravesical lidocaine for bladder biopsy and transurethral bladder
      tumor resection/fulguration was associated with higher patient satisfaction
      compared to previous treatments (p<0.00002). In contrast, electromotive
      intravesical lidocaine was insufficient for 3 of 6 transurethral prostatic
      resections. The cost per patient was about $146 Cdn less with electromotive
      intravesical lidocaine than with conventional general/spinal anesthesia.
      CONCLUSIONS: Electromotive intravesical lidocaine may be a safe, effective and
      affordable form of anesthesia for the ambulatory care of patients requiring
      transurethral bladder biopsy, resection or fulguration with a potential for cost
      savings.

PMID- 9915432
TI  - Sexual function following high energy microwave thermotherapy: results of a
      randomized controlled study comparing transurethral microwave thermotherapy to
      transurethral prostatic resection.
AB  - PURPOSE: We evaluate changes in sexual function in patients treated with high
      energy transurethral microwave thermotherapy compared to transurethral resection
      of the prostate. MATERIALS AND METHODS: A total of 147 patients randomized to
      undergo transurethral microwave thermotherapy or transurethral resection of the
      prostate were asked to complete a self-administered questionnaire evaluating
      sexual function before, and 3 and 12 months after treatment. The questionnaire
      dealt with such items as social status, libido, quality of erection, ejaculation
      and overall satisfaction of sexual functioning. RESULTS: There was a
      statistically significant improvement of micturition in both groups. The
      improvement in the transurethral prostatic resection group was significantly
      better than in the transurethral microwave thermotherapy group. Antegrade
      ejaculation occurred at 3 months following treatment in 27% of the transurethral
      prostatic resection group compared to 74% of the transurethral microwave
      thermotherapy group and at 1 year in 37 and 67%, respectively. Significantly more
      patients undergoing transurethral prostatic resection (36%) had changes in sexual
      function compared to the transurethral microwave thermotherapy group (17%). The
      transurethral microwave thermotherapy group was more satisfied with the sex life.
      Of these patients 55% graded sex as very satisfying compared to 21% in the
      transurethral prostatic resection group. The severity of symptoms was not
      correlated with sexual function in this study. In general, older patients had
      sexual dysfunction more often, while younger patients had pain during sexual
      activities more frequently. CONCLUSIONS: Although clinically less effective, high
      energy transurethral microwave thermotherapy is a better therapeutic option than
      surgery for patients who want to preserve sexual function. In particular
      ejaculation is often preserved after transurethral microwave thermotherapy while
      there is significant deterioration following transurethral prostatic resection.
      In general, older patients have greater sexual dysfunction.

PMID- 9915433
TI  - Long-term incidence of acute myocardial infarction after open and transurethral
      resection of the prostate for benign prostatic hyperplasia.
AB  - PURPOSE: Acute myocardial infarction was found to be the main cause of increased
      long-term mortality in patients after transurethral compared to open
      prostatectomy in various retrospective studies. We performed a randomized
      prospective study to compare morbidity and incidence of acute myocardial
      infarction in patients after transurethral compared to open prostatectomy for
      benign prostatic hyperplasia. MATERIALS AND METHODS: We studied 365 patients who
      were assigned to transurethral (236) or open (129) prostatectomy only according
      to the size of the prostate and who were followed for 7 to 8 years. The clinical
      status of the patients in both groups before and after the operation was
      compared, and the rate of myocardial infarction and long-term mortality was
      studied. RESULTS: More patients with a history of cerebrovascular accident (5.4
      versus 0.8%) and indwelling catheters (16.3 versus 7.6%) before the operation
      were in the open prostatectomy group. Among the 236 patients operated on
      transurethrally 31 were reoperated on (6 more than once) during followup compared
      to 4 of the 129 patients who underwent open prostatectomy. In 15 patients from
      the transurethral prostatectomy group myocardial infarction developed compared to
      9 patients in the open prostatectomy group. This difference was not statistically
      significant. The rate of acute myocardial infarction after prostatectomy, no
      matter which approach was used, was greater than 6% and it appeared to be higher
      when compared to the rate of infarction in the general population of the same age
      group, which is approximately 2.5% in our county. There was no statistically
      significant difference in the overall mortality rate between the transurethral
      and open prostatectomy groups, which was 14.4 and 8.5% respectively. CONCLUSIONS:
      Open prostatectomy is more effective in overcoming urinary obstruction than the
      transurethral approach. No significant differences in myocardial infarction or
      overall mortality rates were found between the 2 groups.

PMID- 9915434
TI  - Comparison of digital rectal examination and biopsy results with the radical
      prostatectomy specimen.
AB  - PURPOSE: Digital rectal examination is integral to staging prostate cancer.
      Ultrasound guided biopsy establishes the diagnosis, and it may provide useful
      information regarding disease grade and extent. Treatment decisions are largely
      based on information gained from digital rectal examination and biopsy but this
      information is only useful if it correlates with the radical prostatectomy
      specimen and prognosis. We correlated digital rectal examination and transrectal
      ultrasound guided biopsy results with a detailed analysis of the radical
      prostatectomy specimen. MATERIALS AND METHODS: The accuracy of an abnormal
      digital rectal examination for predicting the location and extent of cancer was
      assessed in 89 patients thought to have clinical stage T2 disease. We evaluated
      155 patients with clinical stages T1c and T2 disease to correlate the location of
      positive biopsies with the tumor site in the prostate. Radical prostatectomy
      specimens were completely sectioned at 2 mm. intervals, and tumor extent and
      location were recorded. RESULTS: In 85 patients a unilateral lesion was
      suspicious on digital rectal examination, that is stage cT2. The final
      pathological review revealed cancer on the suspicious side in 82 cases (96%) with
      tumor confined to the same lobe in only 23 (27%), bilateral disease in 59 (69%)
      and tumor confined to the contralateral lobe in 3 (4%). In 4 patients with a
      palpable bilateral abnormality a bilateral lesion was confirmed on final
      pathological evaluation. Digital rectal examination demonstrated a 36 and 31%
      incidence of extracapsular tumor extension and positive surgical margins,
      respectively, on the clinically benign side. In 100 patients only unilateral
      biopsy was positive. The final pathological evaluation revealed cancer in the
      biopsy positive side in 95 cases (95%) with tumor confined to the ipsilateral
      lobe in only 26 (26%), bilateral disease in 69 (69%) and tumor confined to the
      contralateral lobe in 5 (5%). In 46 of the 55 patients (84%) with bilateral
      positive biopsies tumor involved both sides but the pathologist did not identify
      cancer in both lobes in 9 (16%). While 100 patients had a unilateral negative
      biopsy, analysis of the prostatectomy specimen revealed carcinoma in the benign
      lobe in 74 (74%). Moreover, extracapsular tumor extension and a positive surgical
      margin were observed on the biopsy negative side in 31% of the patients. The
      degree to which digital rectal examination and biopsy results confirmed the final
      pathological evaluation was assessed using the kappa statistic, which revealed
      only slight agreement with each factor. The correlation of digital rectal
      examination and biopsy results with the location of extracapsular extension and
      positive margins was evaluated by the Spearman coefficient of correlation, which
      indicated poor agreement. When patients with unilateral versus bilateral positive
      biopsy were compared with respect to prognostic parameters, the difference was
      statistically significant for initial serum prostate specific antigen, the
      percentage of surface involved by tumor, biopsy and final Gleason scores, and the
      incidence of extracapsular extension of tumor. CONCLUSIONS: Digital rectal
      examination and the interpretation of prostate biopsy are not accurate clinical
      tools for defining the location and extent of prostatic carcinoma. Bilateral
      positive biopsy may be useful as an adjunct to the current clinical staging
      system.

PMID- 9915435
TI  - Pathological features and prognostic significance of prostate cancer in the
      apical section determined by whole mount histology.
AB  - PURPOSE: We test the hypothesis that cancer in the apical section of the prostate
      is an important independent factor in predicting the progression of clinically
      localized prostate cancer. MATERIALS AND METHODS: We analyzed clinical data and
      whole mount histological step sections for 500 patients who had undergone radical
      retropubic prostatectomy for clinically localized prostate cancer. RESULTS:
      Cancer was in the apex of the prostate in 175 patients (35%). These patients had
      a larger cancer and higher incidence of positive surgical margins, and were more
      likely to have a poorly differentiated cancer than the 325 patients without
      cancer in the apex. However, the presence of apical cancer was not a significant
      predictor of clinical or prostate specific antigen progression in either
      univariate or multivariate Cox proportional hazards models when analyzed for the
      entire group or only in patients with tumor confined to the prostate.
      CONCLUSIONS: Apical cancer in a radical prostatectomy specimen is simply a sign
      of a larger volume cancer and is not independently associated with an increased
      risk of clinical or prostate specific antigen progression.

PMID- 9915437
TI  - A feasibility study of cryotherapy followed by radical prostatectomy for locally
      advanced prostate cancer.
AB  - PURPOSE: There has been a significant shift toward multimodality therapy to try
      to eradicate extracapsular disease better in patients with locally advanced
      prostate cancer. We assess the feasibility and complications of initial
      cryotherapy followed by radical prostatectomy, and evaluate the frequency and
      location of viable benign and malignant prostate tissue and positive surgical
      margins after this treatment combination. MATERIALS AND METHODS: A total of 12
      patients with clinical stage T3 cancer or clinical stages T1c to T2, Gleason
      score 8 to 10 cancer on the initial biopsy were treated with initial cryotherapy
      followed by open surgical exploration 2 to 8 days later. If pelvic lymph nodes
      were negative, radical prostatectomy was performed. Prostate specific antigen was
      measured approximately every 3 months postoperatively, and complications were
      assessed by retrospective chart review and a quality of life survey. RESULTS:
      Radical prostatectomy was aborted in 5 patients with positive pelvic lymph nodes.
      Of the 7 patients who underwent prostatectomy 4 had no residual prostate cancer
      in the specimen (pathological stage pT0 disease). All 7 of these patients had
      focal areas of viable normal prostate glands. Only 1 of the 7 patients had a
      positive surgical margin and biochemical failure (mean followup 22.6 months). The
      main complications of cryotherapy followed by radical prostatectomy were urinary
      incontinence and impotence. CONCLUSIONS: Neoadjuvant cryotherapy achieved
      complete tumor destruction in 4 of 7 patients with locally advanced prostate
      cancer. Cryotherapy followed by radical prostatectomy was associated with
      substantial morbidity, mainly in terms of urinary incontinence.

PMID- 9915438
TI  - Recovery of health related quality of life in the year after radical
      prostatectomy: early experience.
AB  - PURPOSE: We determined the temporal course of patient return to baseline quality
      of life after treatment with radical prostatectomy for early stage prostate
      cancer. MATERIALS AND METHODS: After establishing a longitudinal observational
      database of men undergoing radical retropubic prostatectomy we used established,
      validated quality of life questionnaires (RAND 36-Item Health Survey and
      University of California, Los Angeles Prostate Cancer Index) to document changes
      in general and disease specific health related quality of life (HRQOL). We
      assessed 90 patients at baseline before surgery and then at 3-month intervals for
      1 year postoperatively. Logistic regression was used to explore predictors of the
      return to baseline. RESULTS: After prostatectomy patients had a significant
      decrease in all domains of HRQOL. Return to baseline was rapid in the general and
      bowel domains with at least two-thirds to three-fourths of patients reaching
      pretreatment levels within 6 months of surgery. Return to baseline was slower in
      the urinary and sexual function domains with 61 and 31% of the men, respectively,
      reaching pretreatment levels by 1 year after surgery. Of those who reached
      baseline the average intervals for the bowel, sexual and urinary domains were 5,
      6 and 7 months, respectively. Married and white patients were more likely to
      achieve a return to baseline HRQOL during year 1 postoperatively. However,
      education level was inversely associated with the likelihood of returning to
      baseline. CONCLUSIONS: During the year after radical prostatectomy for early
      stage prostate cancer patient quality of life steadily improved. By 3 months
      postoperatively 30 to 40% of the patients had already recovered baseline levels
      of physical, mental and social functioning, and by 6 months more than 70% had
      reached baseline in the general HRQOL domains. By 12 months after surgery 86 to
      97% of the patients had returned to baseline levels in each domain. Each domain
      continued to improve throughout the year. For the patients who reached baseline
      general HRQOL during followup average recovery time was 5 to 6 months.

PMID- 9915436
TI  - Deferred treatment of locally advanced nonmetastatic prostate cancer: a long-term
      followup.
AB  - PURPOSE: We prospectively investigated long-term survival in select men with
      locally advanced, nonmetastatic prostate cancer managed with deferred treatment.
      MATERIALS AND METHODS: A total of 50 patients with prostate cancer clinically
      outside the prostatic capsule and without distant metastases were included in a
      surveillance protocol. The men were treated if and when symptoms occurred or upon
      request. The series was followed until December 1994. No patient was lost to
      followup. RESULTS: Median patient age at diagnosis was 71 years. All patients
      were followed more than 144 months or died before then. Actual (cumulative
      incidence) overall and disease specific survival rates at 5, 10 and 12 years were
      68 and 90, 34 and 74, and 26 and 70%, respectively. A third of the patients had
      not received antitumor treatment at followup or before death. CONCLUSIONS: When
      managed with deferred treatment nonpoorly differentiated, locally advanced
      nonmetastatic prostate cancer seems to have a poorer survival outcome than
      similarly managed clinically localized prostate cancer. However, compared with
      other treatments and in terms of survival deferred treatment may be an option for
      select patients with such tumors and a life expectancy of 10 years or less.

PMID- 9915439
TI  - Current followup strategies after radical prostatectomy: a survey of American
      Urological Association urologists.
AB  - PURPOSE: Followup care of men who have undergone potentially curative surgical
      treatment for prostate cancer varies widely among clinicians. To determine
      current practice patterns we mailed a custom designed questionnaire to American
      and nonAmerican urologists who were American Urological Association (AUA)
      members. MATERIALS AND METHODS: Surveys were mailed to a random sample of the
      approximately 12,000 AUA members, comprising 3,205 Americans and 1,262
      nonAmericans. Evaluable surveys were returned by 760 American (24%) and 290
      nonAmerican (23%) urologists. Our analysis is based on these 1,050 responses.
      RESULTS: In generally healthy patients after radical prostatectomy for stages T1
      to 2NOMO and T3a to cNOMO prostate cancer the most frequently recommended
      followup diagnostic tests included office visit with digital rectal examination,
      serum prostate specific antigen (PSA) and urinalysis. Although there is
      appreciable variation in the frequency of use of these methods, respondents
      generally recommended office visit with digital rectal examination, serum PSA and
      urinalysis every 3 months in year 1, every 6 months in years 2 to 5 and annually
      thereafter. Other tests, such as serum prostatic acid phosphatase, bone scan, and
      abdominal and pelvic computerized tomography and magnetic resonance imaging, are
      rarely recommended. CONCLUSIONS: Our survey provides information regarding
      current followup strategies recommended by AUA urologists after radical
      prostatectomy for stages T1 to 2NOMO and T3a to cNOMO disease. Office visits and
      digital rectal examination, urinalysis and PSA measurement are the main tools
      that urologists currently use. Although optimal strategy remains unknown, these
      data permit the rational design of clinical trials of alternate followup
      strategies based on actual current practice to answer this important question.

PMID- 9915440
TI  - Mortality of patients with clinically localized prostate cancer treated with
      observation for 10 years or longer: a population based registry study.
AB  - PURPOSE: We studied the outcome in patients with early and probably organ
      confined prostate cancer who were considered candidates for curative therapy and
      treated expectantly. MATERIALS AND METHODS: The study included 2,570 patients
      with newly diagnosed prostate cancer reported to the Danish Cancer Registry from
      1943 to 1986 and surviving for 10 years or longer. Mortality and causes of death
      were analyzed and stratified by stage, age and time of diagnosis. Excess
      mortality was calculated from life expectancy tables for the general population.
      RESULTS: An overall excess mortality (standard mortality ratio 1.58, 95%
      confidence interval [95% CI] 1.51 to 1.65) was found. Young age and advanced
      clinical stage at diagnosis entailed a higher risk of death from prostate cancer.
      Overall 42.7 and 19.1% of the patients who died had prostate cancer as the direct
      or contributing cause of death, respectively. Of the annual deaths 13% were
      attributable to prostate cancer. In 1,326 patients 55 to 64 and 65 to 74 years
      old with clinically localized prostate cancer at diagnosis the excess mortality
      was still significant (standard mortality ratio 1.72, 95% CI 1.54 to 1.93 and
      1.50, 95% CI 1.39 to 1.62, respectively). Prostate cancer was the primary or
      contributing cause of death in 42.9% of the younger group and 21.5% of the older
      group. In these patients 15% of the annual deaths were related to prostate
      cancer. CONCLUSIONS: Patients with clinically localized prostate cancer for 10
      years or longer, who were likely candidates for curative therapy when diagnosed,
      had significant excess mortality when treated expectantly.

PMID- 9915441
TI  - Decline in prostate cancer mortality from 1980 to 1997, and an update on
      incidence trends in Olmsted County, Minnesota.
AB  - PURPOSE: We describe trends in prostate cancer mortality from 1980 to 1997,
      before and after the introduction of serum prostate specific antigen (PSA)
      testing to the community medical practice, and provide an update on trends in
      incidence since 1992. MATERIALS AND METHODS: All men with a diagnosis of prostate
      cancer who died between 1980 and 1997 were identified and parts 1 and 2 of the
      death certificates were reviewed for a diagnosis of prostate cancer. In addition,
      all men with biopsy proved prostate cancer diagnosed between 1983 and 1995 were
      identified. The complete medical records of incident cases of prostate cancer
      were reviewed for signs and symptoms at diagnosis and for the first treatment
      received. RESULTS: Age adjusted, community mortality rates from prostate cancer
      increased from 25.8/100,000 men in 1980 to 1984 to a peak of 34/100,000 in 1989
      to 1992, and have since declined to 19.4/100,000 in 1993 to 1997 (22% decline in
      mortality, 95% confidence interval 49% decline to 17% increase). The overall age
      adjusted incidence rates which peaked at 209/100,000 person-years in 1992 as
      previously reported declined to 108/100,000 in 1993 and 132/100,000 in 1995. A
      similar pattern was observed for organ confined cancers. However, incidence rates
      for regional or distant disease were suggestive of a continuing downward trend
      from 1989 to 1992 compared to 1993 to 1995 (12% decline per year, p = 0.07).
      CONCLUSIONS: These data demonstrate that despite the increase in prostate cancer
      mortality rates in the mid to late 1980s, mortality rates in 1993 to 1997 are
      lower than in the years before serum PSA testing. While chance cannot be ruled
      out, the data suggest that increased screening for prostate cancer, particularly
      through PSA testing, may have led to declines in mortality from prostate cancer.

PMID- 9915442
TI  - A comparison of noncontrast computerized tomography with excretory urography in
      the assessment of acute flank pain.
AB  - PURPOSE: We compare noncontrast enhanced computerized tomography (CT) and
      excretory urography (IVP) in the evaluation of acute flank pain. MATERIALS AND
      METHODS: A total of 40 consecutive patients presenting to the emergency
      department with acute flank pain were evaluated with noncontrast CT, films of the
      kidneys, ureters and bladder, and IVP. The patients were treated according to the
      clinical picture. All 40 sets of evaluations were later assessed randomly by an
      independent consultant radiologist for the presence, size and location of a
      stone, ureteral dilatation and secondary signs of ureteral obstruction. RESULTS:
      Of 40 patients 12 had no calculus and 28 had a calculus confirmed on removal or
      documented passage of a stone. Absence of a stone was based on clinical and
      radiological followup with clinical resolution. CT revealed all 28 calculi and no
      calculus in 11 of 12 patients with 100% sensitivity and 92% specificity. IVP
      demonstrated 18 calculi (64% sensitivity) and no calculus in 11 of 12 patients
      (92% specificity). Ureteral obstruction was seen in 28 of the 40 patients, and CT
      and IVP were equivalent in detection (100% sensitivity). Films of the kidneys,
      ureters and bladder alone demonstrated 15 of 28 stones (54% sensitivity).
      CONCLUSIONS: Noncontrast CT is an accurate, safe, rapid technique to assess acute
      flank pain, and the evaluation of choice for patients who would otherwise require
      IVP for diagnosis.

PMID- 9915443
TI  - Upper tract urokinase instillation for nephrostomy tube patency.
AB  - PURPOSE: We describe a useful technique for declotting a nephrostomy tube blocked
      secondary to recurrent blood clot formation. MATERIALS AND METHODS: Urokinase was
      instilled into the nephrostomy tube in a patient with a solitary kidney
      obstructed by malignancy on 2 separate occasions for 30 minutes each followed by
      manual irrigation with normal saline. RESULTS: The nephrostomy tube and renal
      pelvis were successfully declotted, and we avoided a nephrostomy tube change or
      insertion of a second tube. The tumor was subsequently embolized to prevent
      further bleeding. CONCLUSIONS: Instillation of urokinase into a nephrostomy tube
      blocked by a blood clot may obviate repeat nephrostomy tube changes and is a
      useful addition to the urological armamentarium.

PMID- 9915444
TI  - Retroperitoneoscopic nephroureterectomy for renal pelvic tumors with a single
      iliac incision.
AB  - PURPOSE: Retroperitoneal laparoscopy, by providing direct access to the
      retroperitoneal cavity, is a useful approach to urological surgery. We applied
      this technique to nephroureterectomy in patients with tumors of the renal pelvis.
      MATERIALS AND METHODS: Between January 1995 and March 1997 we performed 4
      retroperitoneal laparoscopic nephroureterectomies in patients with tumors of the
      renal pelvis. The patients were placed in the lateral decubitus position. Five
      trocars were used. Balloon dilation was not contributory. Radical nephrectomy was
      performed and the kidney was left in the retroperitoneal space. Via an iliac
      incision ureterectomy with a bladder cuff was performed and the specimen was
      removed (kidney and ureter) en bloc via this incision without opening the urinary
      tract. RESULTS: One right and 3 left nephroureterectomies were performed with an
      average operating time of 220 minutes (range 160 to 300). Average kidney size was
      110 mm. (range 100 to 120). Average hospital stay was 5.7 days (range 5 to 7).
      Blood loss was minimal and postoperative analgesic requirements were moderate.
      Conversion to open surgery was never necessary. The morbidity rate was zero. The
      pathological stages were pT2 G2, pT3 G2, pT3G3 and pT3 G2-G3 N+. A local
      recurrence was observed in a patient with a pT3 G3 tumor. CONCLUSIONS:
      Nephroureterectomy can be performed by retroperitoneal laparoscopy. The
      perioperative morbidity and hospital stay are reduced. Further followup is
      required to evaluate long-term results in terms of cancer outcome.

PMID- 9915445
TI  - Radical cystoprostatectomy: an extraperitoneal retrograde approach.
AB  - PURPOSE: We describe a new technical approach for the surgical management of
      bladder cancer. MATERIALS AND METHODS: Patients with invasive bladder cancer
      underwent radical cystoprostatectomy using a technically different approach than
      the conventional method. The important features of this modification include a
      small infraumbilical incision, completely extraperitoneal dissection to maintain
      the bowel loops away from the operating field, urethral dissection performed
      earlier in the operation rather than at the end to preserve the striated urethral
      sphincter with the neurovascular bundles, completely retrograde dissection of the
      rectovesical plane for increased safety and reperitonealization done at
      completion to isolate the urinary anastomoses from the bowel anastomosis.
      RESULTS: More than 50 consecutive patients with early bladder cancer underwent
      this operation during a 2-year period. The technique was safe and satisfactory.
      CONCLUSIONS: Radical retrograde extraperitoneal cystoprostatectomy is based on a
      finer knowledge of anatomy. It requires accurate dissection, making it inherently
      superior to the conventional method.

PMID- 9915446
TI  - Epidemiology of interstitial cystitis: a population based study.
AB  - PURPOSE: Interstitial cystitis is a chronic and debilitating syndrome but
      surprisingly little is known about its epidemiology. This study was designed to
      estimate the prevalence of interstitial cystitis among women in the United
      States. MATERIALS AND METHODS: Female participants in the Nurses' Health Study
      (NHS) I and II (184,583) were asked by mailed questionnaires whether they had
      ever been diagnosed with interstitial cystitis. We requested and reviewed medical
      records of women self-reporting interstitial cystitis. The accuracy of self
      reports was evaluated using standardized criteria. RESULTS: Among the 93,428
      women who responded to the NHS II questionnaire and 91,155 women who responded to
      the NHS I questionnaire 1,354 (1.4%) and 357 (0.4%), respectively, self-reported
      interstitial cystitis. Based on medical record review 63 cases of interstitial
      cystitis were confirmed in NHS II and 47 in NHS I. The prevalence of interstitial
      cystitis was 67/100,000 women in NHS II and 52/100,000 in NHS I. There was no
      substantial variation in prevalence by age. CONCLUSIONS: The prevalence of
      interstitial cystitis in the United States is more than 50% greater than
      previously reported and 3-fold greater than that reported in Europe.

PMID- 9915447
TI  - The diagnosis of interstitial cystitis revisited: lessons learned from the
      National Institutes of Health Interstitial Cystitis Database study.
AB  - PURPOSE: The lack of a precise working definition of interstitial cystitis may
      have resulted in the de facto use of the National Institute of Diabetes,
      Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We
      evaluated these strict criteria in light of the broader inclusion criteria for
      patients evaluated in the Interstitial Cystitis Database study to determine their
      utility in clinical practice as a useful basis for the diagnosis of interstitial
      cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for
      the Interstitial Cystitis Database before January 1, 1996 met the basic criteria
      of urinary frequency, urgency or pain for at least 6 months in duration without a
      diagnosable etiology. Of these patients 148 underwent cystoscopy and
      hydrodistention of the bladder as a part of the evaluation. All patients were
      followed for a minimum of 1 year. Comparisons were made between patients judged
      to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK
      research definition of the syndrome. RESULTS: Almost 90% of patients potentially
      meeting NIDDK criteria are believed by experienced clinicians to have
      interstitial cystitis, confirming the research value of these criteria in
      defining a homogeneous population for study. However, strict application of NIDDK
      criteria would have misdiagnosed more than 60% of patients regarded by
      researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS:
      The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic
      definition of interstitial cystitis.

PMID- 9915448
TI  - A randomized double-blind trial of oral L-arginine for treatment of interstitial
      cystitis.
AB  - PURPOSE: Nitric oxide synthase activity is decreased in the urine of patients
      with interstitial cystitis compared to the urine of controls. In a preliminary
      trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary
      nitric oxide synthase activity and improved interstitial cystitis symptoms. This
      randomized, double-blind, placebo controlled study further investigates the
      efficacy of L-arginine treatment for interstitial cystitis. MATERIALS AND
      METHODS: A total of 53 interstitial cystitis patients were assigned to receive
      daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis
      symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. RESULTS:
      The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26
      in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L
      arginine group and 8% (2 of 25) in the placebo group were clinically improved by
      the end of the trial (p = 0.07). A Likert scale showed greater global improvement
      in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of
      25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and
      tendency toward improvement in urgency (p = 0.06) and frequency of pain (p =
      0.09). Using an intention to treat approach to analysis there were no differences
      between groups. CONCLUSIONS: Oral L-arginine (1,500 mg. daily) may decrease pain
      and urgency in a subset of interstitial cystitis patients.

PMID- 9915449
TI  - The O'Conor technique: the gold standard for supratrigonal vesicovaginal fistula
      repair.
AB  - PURPOSE: Several techniques have been used for repair of vesicovaginal fistula.
      Although surgical success is achieved in the majority of cases, a 4 to 35%
      failure rate occurs when a transvesical or transvaginal approach is used. We
      investigated the clinical efficacy of the O'Conor transperitoneal supravesical
      technique for supratrigonal vesicovaginal fistula. MATERIALS AND METHODS: A total
      of 29 patients with iatrogenic supratrigonal vesicovaginal fistula following
      hysterectomy or cesarean section were studied. An initial operation and prior
      attempts at fistula repair had been performed in 9 patients (34%) for benign (26)
      or malignant (3) uterine conditions. All patients were treated with the O'Conor
      technique 6 weeks to 48 months (median 8 weeks) after fistula diagnosis. RESULTS:
      The vesicovaginal fistula was successfully corrected in all patients at the first
      attempt and only 1 had stress urinary incontinence associated with urethral
      incompetence. No significant bladder dysfunction or decrease in bladder capacity
      was seen after repair. CONCLUSIONS: Considering the inferior clinical results of
      the transvaginal and transvesical approaches compared to the O'Conor technique
      for repair of supratrigonal vesicovaginal fistula, it would be unethical to
      conduct a randomized study to prove the superiority of the latter method. We
      suggest that the O'Conor technique be considered the gold standard surgical
      method of repair of supratrigonal vesicovaginal fistulas.

PMID- 9915450
TI  - Anatomical anterior exenteration with urethral and vaginal preservation:
      illustrated surgical method.
AB  - PURPOSE: We describe in detail a method for urethral and vaginal preservation in
      women considering orthotopic urinary tract reconstruction after bladder removal.
      MATERIALS AND METHODS: We retrospectively reviewed the pathological reports of
      patients treated with anterior exenteration at our hospital between 1984 and 1997
      for specific evidence of urethral, vaginal, cervical or uterine involvement by
      the primary bladder tumor. Based on our findings we describe our approach to
      anterior exenteration in 6 patients. RESULTS: A total of 46 patients were treated
      at our center with en bloc anterior exenteration and pelvic lymphadenectomy for
      primary bladder cancer between 1984 and 1997. In 7 patients (15%) pathological
      review of the surgical specimen documented urethral involvement by the primary
      tumor. In 1 patient (2%) microscopic evidence of tumor was identified in the
      cervix and 1 (2%) had tumor extension to the vagina documented in the final
      pathology report. CONCLUSIONS: The observed rates of vaginal and urethral
      involvement agree with those reported by others, and suggest that in the majority
      of women treated with anterior exenteration sacrifice of the urethra and vagina
      is usually not necessary from an oncological perspective. This procedure is
      particularly appropriate in women concerned with postoperative sexual function
      and those considering orthotopic reconstruction of the lower urinary tract after
      exenterative bladder cancer surgery.

PMID- 9915451
TI  - Long-term experience with orthotopic reconstruction of the lower urinary tract in
      women.
AB  - PURPOSE: We investigated the long-term outcome of orthotopic neobladders in
      women. MATERIALS AND METHODS: At our institutions 8 women have undergone lower
      urinary tract reconstruction with an orthotopic neobladder and have been followed
      for more than 4 years. After urethral sparing cystectomy the neobladder was
      constructed and connected to the native urethra. Late complications were
      analyzed, and voiding function was evaluated by a pressure flow micturition study
      and bead-chain cystourethrography. RESULTS: No late complications related to the
      surgery were noted. Of the 8 patients 7 were completely dry day and night. Four
      patients with ileal neobladder required clean intermittent catheterization, and
      hypercontinence might have been caused by downward migration of the neobladder
      and reduced neobladder pressure at voiding. No recurrence in the native urethra
      was noted, and all patients were satisfied postoperatively. CONCLUSIONS: These
      results of orthotopic neobladder in women are encouraging. Overall patient
      satisfaction was excellent. An international collaborative study is necessary to
      achieve the number of patients required to determine the ideal orthotopic
      neobladder for women.

PMID- 9915452
TI  - Bladder neck competency at rest in women with incontinence.
AB  - PURPOSE: We determine the presence of an open bladder neck during video
      urodynamic studies and relate that finding to the presence of stress urinary
      incontinence. MATERIALS AND METHODS: Patients presenting with urinary
      incontinence, voiding dysfunction or pelvic floor prolapse underwent video
      urodynamics. With the patient upright and after 200 ml. contrast material had
      been instilled into the bladder the bladder neck was viewed to determine if it
      was open or closed. At that point the abdominal leak point pressure was measured.
      RESULTS: Of 102 women, average age 56.5 years (range 31 to 82), 13% had an open
      bladder neck and demonstrable stress incontinence on video urodynamics with an
      average abdominal leak point pressure of 45 cm. water (range 26 to 90). Of those
      with stress incontinence on urodynamics 23% had an open bladder neck. No
      continent patient had an open bladder neck. CONCLUSIONS: The presence of an open
      bladder neck with the bladder filled to 200 ml. correlates strongly with the
      presence of stress incontinence.

PMID- 9915453
TI  - The effect of genital prolapse on voiding.
AB  - PURPOSE: We determined whether genital prolapse causes obstruction that may be
      relieved by a vaginal pessary as well as the degree to which voiding difficulty,
      urethral hypermobility, bladder outlet obstruction, occult stress incontinence,
      detrusor instability and impaired detrusor contractility are associated with
      prolapse. MATERIALS AND METHODS: We prospectively evaluated 60 women with a mean
      age of 52 years who had genital prolapse, including 35 (58%) with grade 1 or 2
      and 25 (42%) with grade 3 or 4 cystocele, using pressure-flow video urodynamics
      and cotton swab testing. Leak point pressure and uroflowmetry were repeated in
      patients with severe prolapse after insertion of a ring pessary. RESULTS:
      Urethral hypermobility (p<0.05) and symptoms of voiding difficulty (p<0.01) were
      more common in women with grade 3 or 4 cystocele. Urodynamics revealed bladder
      outlet obstruction in 2 patients (4%) with grade 1 or 2 cystocele and 18 (58%)
      with grade 3 or 4 cystocele (p<0.001). After vaginal pessary placement bladder
      outlet obstruction reverted to normal free flow in 17 women (94%) with grade 3 or
      4 cystocele. Seven women (20%) with grade 1 or 2 cystocele versus 13 (52%) with
      grade 3 or 4 cystocele had detrusor instability (p<0.05). Impaired detrusor
      contractility was noted in each group (p>0.05). In patients with stress
      incontinence intrinsic sphincter deficiency did not correlate with the degree of
      prolapse and urethral hypermobility did not correlate with leak point pressure.
      CONCLUSIONS: Lower urinary tract symptoms are common in women with genital
      prolapse. Voiding difficulty, bladder outlet obstruction and occult stress
      incontinence may coexist and they are associated with prolapse. Detrusor
      instability and urethral hypermobility also correlate with the degree of prolapse
      but impaired detrusor contractility and intrinsic sphincter deficiency do not. In
      women with severe prolapse ring pessary reduction of prolapse during urodynamics
      is useful to determine symptomatic and occult conditions.

PMID- 9915454
TI  - 4-Defect repair of grade 4 cystocele.
AB  - PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe
      deficiencies of vesicourethral support. We describe this technique used during
      pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period
      130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele
      using the 4-defect repair technique. Cystocele repair had been performed in 60
      patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost
      incision" is used in the vaginal wall to facilitate separation of the wall from
      underlying perivesical fascia, entry into the retropubic space, and exposure of
      the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4
      polypropylene sutures are used to provide an anterior vaginal wall sling which is
      modified to incorporate perivesical fascia and cardinal ligaments. Central defect
      repair is achieved by approximation of the cardinal ligaments and midline
      plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112
      patients were available for followup which ranged from 6 to 42 months (mean 21).
      Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94
      patients (83%), including rectocele repair in 81, hysterectomy in 22 and
      enterocele repair in 31. Of the patients 92% had excellent objective and
      subjective results for anatomical cystocele repair. Of the patients with
      preoperative stress urinary incontinence 90% had excellent or good subjective
      results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4
      defect repair technique relies on anatomical restoration of 4 distinct
      deficiencies of pelvic support and is highly effective for relief of symptoms of
      grade 4 cystocele.

PMID- 9915455
TI  - Heterotopic adrenal cortical adenoma masquerading as metastatic renal cell
      carcinoma.

PMID- 9915457
TI  - Radio frequency ablation of renal cell carcinoma via image guided needle
      electrodes.

PMID- 9915456
TI  - 111Indium-capromab pendetide unexpectedly localizes to renal cell carcinoma.

PMID- 9915458
TI  - Correction of dermal contour defect with collagen injection: a simple management
      technique for difficult stomal care.

PMID- 9915459
TI  - Urinary filariasis presenting as bladder pseudotumors.

PMID- 9915460
TI  - Large nephrogenic adenoma following transurethral resection of the prostate.

PMID- 9915461
TI  - Syncope from increased ventricular response in atrial fibrillation during
      voiding: a new indication for surgical management in benign prostatic
      hyperplasia.

PMID- 9915462
TI  - Fluorodeoxyglucose positron emission tomography scan of prostate cancer bone
      metastases with flare reaction after endocrine therapy.

PMID- 9915463
TI  - Re: Delayed hypersensitivity and systemic arthralgia following transurethral
      collagen injection for stress urinary incontinence.

PMID- 9915464
TI  - Re: Long-term results of the Stamey bladder neck suspension: direct comparison
      with the Marshall-Marchetti-Krantz procedure.

PMID- 9915465
TI  - Re: Reconstruction of deformities resulting from penile enlargement surgery.

PMID- 9915466
TI  - Re: Male pelvic anatomy reconstructed from the visible human data set.

PMID- 9915467
TI  - Re: Catheter-free endoscopic laser ablation of the prostate using a 1-size
      prostatic stent.

PMID- 9915468
TI  - Re: 5-Year outcome of surgical resection and watchful waiting for men with
      moderately symptomatic benign prostatic hyperplasia: a Department of Veterans
      Affairs cooperative study.

PMID- 9915469
TI  - Re: Editorial comment--The results of prostate carcinoma screening in the U.S. as
      reflected in the surveillance, epidemiology, and end results program.

PMID- 9915470
TI  - Urological manifestations of the Wolfram syndrome: observations in 14 patients.
AB  - PURPOSE: Since the initial description of the Wolfram syndrome, various anomalies
      have been associated with this rare entity. Urinary tract dilatation and bladder
      dysfunction, usually in the form of a large, atonic bladder, are coexisting
      features of this syndrome that are commonly believed to be secondary to high
      urine output in diabetes insipidus. The presentation and nature of the urological
      manifestations of this syndrome remain controversial due to the lack of large
      series in the literature. We evaluated the urological manifestations of this rare
      syndrome. To our knowledge we report the largest series of patients (14) with the
      Wolfram syndrome who underwent a complete urological evaluation. MATERIALS AND
      METHODS: Eight boys and 6 girls with a mean age of 13.4 years underwent upper
      tract imaging and a video urodynamic investigation. A multidisciplinary
      consultation was obtained to investigate all components of the syndrome. RESULTS:
      Upper tract dilatation was present in 11 patients. Urodynamics revealed a normal
      bladder in only 1 patient, who also had severe hydronephrosis. Seven patients had
      a low capacity, high pressure bladder, while 6 had an atonic bladder. The type of
      bladder dysfunction did not correlate with time since the onset of diabetes
      mellitus or diabetes insipidus, or the severity of hydronephrosis. Three patients
      with sphincteric dyssynergia also had a hyperreflexic bladder. CONCLUSIONS:
      Contrary to some earlier reports, our findings suggest that bladder dysfunction
      does not always present as a large atonic bladder in the Wolfram syndrome. A low
      capacity, high pressure bladder with sphincteric dyssynergia is also common. The
      presence and duration of other syndrome manifestations do not correlate with the
      type of bladder dysfunction, suggesting that bladder dysfunction may also be a
      primary rather than secondary component of the syndrome.

PMID- 9915471
TI  - Urethral obstruction after primary exstrophy closure: what is the fate of the
      genitourinary tract?
AB  - PURPOSE: We assessed the impact of posterior urethral obstruction after primary
      bladder exstrophy closure. MATERIALS AND METHODS: A review of the records of
      patients with classic bladder exstrophy at our institution identified 29 boys and
      12 girls with a mean age of 11.75 years who had had posterior urethral outlet
      obstruction after closure was done in the neonatal period. RESULTS: Of these 41
      patients 75% underwent closure elsewhere. At closure osteotomies were done in 13
      patients and 23 were younger than 72 hours. Paraexstrophy skin flaps were used at
      primary closure in 27 cases (66%). Obstruction presented as recurrent urinary
      tract infection, upper tract deterioration with or without renal failure, bladder
      stones, difficult catheterization, urethral stitch erosion, a full bladder on
      ultrasound, a prolonged dry interval, urinary retention, inability to
      catheterize, bladder rupture, rectal prolapse and epididymitis or prostatitis.
      Usually the initial obstructive episode developed within 60 days of closure and
      it was recurrent. Therapy included suprapubic catheter placement, vesicostomy,
      ureterostomy, nephrostomy and multiple urethral manipulations, such as dilation
      with or without steroid injection, internal urethrotomy, urethral stitch removal,
      clean intermittent catheterization or open urethroplasty. All 6 patients who
      underwent long-term diversion via vesicostomy, ureterostomy or a conduit for
      greater than 6 months required permanent bowel segments for reconstruction, while
      in 5 of the 6 who underwent short-term diversion via nephrostomy or suprapubic
      tube placement for less than 6 months reconstruction was bowel-free. Of the 36
      children in whom functional reconstruction was performed 9 are undergoing staged
      reconstruction, reconstruction failed in 14, 4 are socially dry and 9 are
      continent. CONCLUSIONS: Posterior urethral obstruction after exstrophy closure
      markedly decreases the success of staged bladder reconstruction, presents a
      significant risk to the upper urinary tract and should be detected early.

PMID- 9915472
TI  - Genitourinary anomalies in the CHARGE association.
AB  - PURPOSE: We identified the incidence and types of genital and urinary anomalies,
      and established a plan for evaluating the urinary system in the CHARGE
      association. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32
      patients in whom the CHARGE association was diagnosed. RESULTS: Of the 32
      patients identified 22 (69%) had genitourinary abnormalities. Genital anomalies,
      including micropenis, penile agenesis, hypospadias, chordee, cryptorchidism, a
      bifid scrotum, atresia of the uterus, cervix and vagina, and hypoplastic labia
      majora, labia minora and clitoris, were present in 18 patients (56%). Of the 24
      patients who underwent renal ultrasound 10 (42%) were diagnosed with urinary
      tract anomalies including a solitary kidney, hydronephrosis, renal hypoplasia and
      duplex kidneys. Further evaluation revealed vesicoureteral reflux, neurogenic
      bladder secondary to spinal dysraphism, nephrolithiasis, ureteropelvic junction
      obstruction and a nonfunctioning upper pole in both duplex kidneys. CONCLUSIONS:
      There is a high incidence of genitourinary anomalies in the CHARGE association.
      Because of this high incidence of anomalies, patients with this condition should
      undergo a careful genitourinary evaluation, including renal and bladder
      ultrasound, and voiding cystourethrography screening.

PMID- 9915474
TI  - Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors
      in hyperplastic and non-hyperplastic human prostate.
AB  - PURPOSE: To determine the expression and localization of the alpha1A-1, alpha1B
      and alpha1D-adrenoceptor (AR) subtypes in hyperplastic and non-hyperplastic human
      prostate tissue. MATERIALS AND METHODS: The expression of the alpha1-AR subtypes
      was examined at the mRNA level by quantitative solution hybridization, and at the
      protein level by immunohistochemistry using subtype selective antibodies.
      RESULTS: While the overall level of alpha1-AR mRNA was not significantly
      different between hyperplastic and non-hyperplastic tissue, there were
      significant differences in the ratio of the alpha1-AR subtypes expressed in the
      two tissue types. The most significant finding from these studies was the reduced
      expression of the alpha1b-AR mRNA in both glandular and stromal hyperplasia. By
      immunohistochemistry, the alpha1A-1-AR was detected in the stroma and not in the
      glandular epithelium. The alpha1B-AR was localized predominantly in the
      epithelium and was weakly present in the stroma. Lower levels of the alpha1B-AR
      were detected in the hyperplastic prostatic epithelium. The alpha1D-AR was
      detected in areas of stroma and was abundantly present in blood vessels.
      CONCLUSIONS: The alpha1A-1-, alpha1B- and alpha1D-AR subtypes are differentially
      localized in human prostate, and the expression levels of all three subtypes are
      altered in BPH. Alterations in a1-AR subtype expression (particularly the alpha1B
      AR) in BPH cannot be solely attributed to changes in tissue morphometry resulting
      from hyperplasia and may be of significance in the pathogenesis of BPH.

PMID- 9915473
TI  - Inducible nitric oxide synthase with transitional cell carcinoma of the bladder.
AB  - PURPOSE: Nitric oxide (NO) plays a critical role as both a cell signaling
      molecule and as a cytotoxic/cytostatic mediator. Nitric oxide synthase (NOS)
      present in macrophages and neutrophils produces NO in response to immune
      stimulation. We evaluated NO production in both bladder tissue and urine from
      patients with transitional cell carcinoma (TCC) of the bladder. MATERIALS AND
      METHODS: Inducible NOS (iNOS) RNA and protein were evaluated in bladder tissue
      from patients with and without TCC. Human iNOS-RNA products were identified with
      the reverse transcriptase-polymerase chain reaction (RT-PCR). Western blot
      analysis using a polyclonal antibody directed against iNOS recognized
      immunoreactive iNOS protein. Using the same iNOS antibody, the distribution of
      iNOS was examined in formalin-fixed, paraffin embedded samples of various grades
      of TCC. NOS activity was measured in the urine particulate fraction from patients
      with TCC and from controls by the conversion of [14C]-L-arginine to [14C]-L
      citrulline. RESULTS: Inducible NOS-RNA products and iNOS specific proteins were
      found in bladder tissue that contained TCC but not in control bladder tissue.
      Inducible NOS was uniformly localized in inflammatory cells within the
      carcinomas. Scattered tumor cells expressed iNOS in 8 of 12 specimens. There was
      no clear relationship between tumor immunoreactivity and tumor grade. NOS
      activity in urine from patients with TCC was not significantly elevated or
      decreased in comparison with control urine. CONCLUSIONS: Inducible NOS is
      expressed by cells comprising and surrounding human bladder tumors. It is
      primarily localized to inflammatory cells, but also is demonstrated within
      individual tumor cells.

PMID- 9915475
TI  - Recovery of distal nephron enzyme activity after release of unilateral ureteral
      obstruction.
AB  - PURPOSE: Unilateral ureteral obstruction (UUO) for 24 hours results in a severe
      compromise of distal tubular function. The acidification defect is believed to be
      localized in the collecting duct. To characterize distal tubular function
      recovery one month after junction release, clearance studies in whole animals and
      enzyme studies in microdissected segments were performed in an experimental model
      of unilateral ureteral obstruction. MATERIALS AND METHODS: Following release of
      ureteral obstruction of 24 hours duration, a significant decrease of whole kidney
      glomerular filtration rate was observed in the postobstructed kidney (POK) with a
      marked increase in urinary pH, fractional excretion of bicarbonate (FEHCO3-) and
      decrease in urinary osmolality. By orthograde stop flow experiment, bicarbonate
      excretion rate (Fr:Ff HCO3-/Fr:Ff Inutest) increased in the first and second
      urine fractions of 120 microl. corresponding to the collecting segment in the
      POK, one day after release. Decrease in U-P pCO2 (p<0.01) suggested an impaired
      H+ secretion on distal nephron in POK. Recovery of inulin clearance and values of
      urinary pH, FEHCO3- and urinary osmolality near contralateral and control kidneys
      were observed thirty days following ureteral release. The decline in enzyme
      activity in the distal nephron due to structural damage from high intratubular
      pressure was evaluated. Bafilomycin sensitive H+ -ATPase activity measurement in
      the medullary collecting duct segments of the POK showed an important decrease
      (68%), with lightly reduced activity (20%) in the cortical collecting duct, 24
      hours after obstruction release. Localized in the connecting tubule cells and
      secreted into the tubular fluid in the late distal nephron, renal kallikrein has
      been involved in bicarbonate transport at cortical collecting duct segments. The
      renal kallikrein-like activity was reduced in POK (p<0.01). RESULTS: Recovery of
      enzyme activity was shown thirty days after unilateral ureteral obstruction. Our
      results show severe functional damage of the collecting duct after 24 hours of
      unilateral ureteral obstruction. H+ -ATPase activity was markedly decreased on
      medullary collecting duct segments. CONCLUSIONS: A correlation between the
      functional impairment of distal H+ secretion and decreased distal nephron enzyme
      activity has been shown. Recovery of both the functional and the enzyme activity
      at the distal nephron was demonstrated thirty days after obstruction release.

PMID- 9915476
TI  - A non-nitrergic smooth muscle relaxant factor released from rat urinary bladder
      by muscarinic receptor stimulation.
AB  - PURPOSE: To study the possible release of a relaxant factor from isolated rat
      bladder tissue. MATERIALS AND METHODS: Thoracic aortae and urinary bladders were
      obtained from 55 female Sprague-Dawley rats. The bladder body was used in its
      original tubular shape as the donor tissue in a co-axial bioassay system, and the
      aorta served as acceptor tissue. RESULTS: In a co-axial bioassay system with
      endothelium-free, norepinephrine-contracted, rat aortic preparations mounted
      within urothelium-intact urinary bladder, carbachol caused a concentration
      dependent relaxation, amounting to 64+/-7% (n = 10) of the induced contraction,
      suggesting release of a relaxing factor. The relaxant effect of carbachol was
      lost if the urinary bladder segment was removed. However, the relaxation was
      affected neither by removal of the urothelium, nor by bladder segment inversion.
      It was resistant to inhibition of the L-arginine/nitric oxide and cyclo-oxygenase
      pathways, and unaffected by beta-adrenoceptor blockade and K+ channel inhibition.
      The relaxation was not associated with any significant changes in the
      intracellular levels of cGMP or cAMP. CONCLUSION: A previously unrecognized non
      adrenergic, non-nitrergic, non-prostanoid inhibitory mediator is released from
      the rat urinary bladder by muscarinic receptor stimulation. The physiological
      importance of such a factor remains to be established.

PMID- 9915477
TI  - Functional anatomy of the male feline urethra: morphological and physiological
      correlations.
AB  - Anatomical and histological methods were combined with measurements of the
      urethral pressure profile (UPP) to investigate the functional aspects of the
      urethra in male cats. A silicone rubber catheter with two microdiaphragm pressure
      transducers was used to measure the UPP. Gross anatomy and ultrastructure of the
      urethra at each segment were examined and correlated with the pressure profile
      data. The preprostatic urethra was composed of three layers of smooth muscle,
      while distal to the prostate striated muscle became predominant. Increased
      baseline pressure and rapid fluctuations in pressure in the postprostatic urethra
      and bulbourethra resulted from the function of periurethral striated musculature.
      The UPP was affected by the bladder pressure, repetition of the measurement, the
      sensor orientation in the urethra, and the type of measurement catheter. Well
      controlled high fidelity measurements enabled a clear correlation to be
      established between the features of the UPP and the anatomy of the urethra and
      surrounding musculature. Additionally, observations on the ultrastructural and
      microscopic anatomy of the urethra extend a previous description of the pelvic
      urethra.

PMID- 9915478
TI  - Measurement of intercellular electrical coupling in guinea-pig detrusor smooth
      muscle.
AB  - PURPOSE: The electrical impedance of detrusor smooth muscle strips to alternating
      current has been measured to calculate the resistance of the intracellular
      pathway, in particular gap junction resistance. Values have been compared with
      myocardium, which is electrically well-coupled. MATERIALS AND METHODS:
      Alternating current was passed along the intracellular pathway of muscle strips
      by creating a high extracellular resistance around the preparation. The data were
      analyzed in terms of an equivalent circuit consisting of an intracellular and
      extracellular pathway. RESULTS: Intracellular resistance was divided into two
      series components, a cytoplasmic resistance and a gap junction resistance.
      Detrusor intracellular resistance was about three times that of myocardium. The
      greater value was attributed to a larger gap-junction resistance. Superfusion of
      detrusor strips with an isosmotic solution of 50% sucrose, 50% Tyrode's increased
      both cytoplasm and gap junction resistances. CONCLUSIONS: Gap-junction resistance
      is larger in detrusor compared with myocardium. However, significant electrical
      current can still pass between adjacent detrusor cells. Calculation of the space
      constant however shows that functionally detrusor is electrically well-coupled
      because of the high membrane resistance. The functional consequences of these
      findings are discussed.

PMID- 9915479
TI  - Distribution of doxorubicin in the bladder wall and regional lymph nodes after
      bladder submucosal injection of liposomal doxorubicin in the dog.
AB  - PURPOSE: Liposome-encapsulated doxorubicin (Lip-Dox) has increased therapeutic
      efficacy and reduced toxicity compared to free doxorubicin (Dox). To assess the
      utility of Lip-Dox for local control of bladder cancer, we examined the
      distribution of Dox in the bladder wall and the regional lymph nodes of dogs
      after bladder submucosal injection of Lip-Dox. MATERIALS AND METHODS: In 8 dogs
      (group SM), Lip-Dox (2 mg.:1 ml.) was injected into the submucosal layer of each
      lateral bladder wall by using a flexible cystoscope. The other 8 dogs (group IV)
      underwent intravenous injection of free Dox (4 mg.). Both groups of animals were
      sacrificed at 1, 3, 5 or 7 days after the injections. The concentration of Dox
      was measured in both the mucosal and muscle layers of 5 bladder wall sites and
      also in the external iliac lymph nodes bilaterally. RESULTS: The Dox
      concentration in the lymph nodes of group SM was significantly higher (about 15
      100 times) than that of group IV throughout the whole follow-up period. The Dox
      concentration in the bladder wall for group SM was significantly higher than that
      in group IV (about 70-930 times at the lateral walls and 2-830 times at the other
      sites). CONCLUSION: The present results demonstrate that Lip-Dox injected into
      the bladder submucosally distributes well, both in the whole bladder wall and in
      regional lymph nodes and remains at a high concentration in these tissues for at
      least one week after injection.

PMID- 9915480
TI  - Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat
      livers.
AB  - PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism
      in rats. MATERIALS AND METHODS: Adult male and female rats were administered a
      precursor of oxalate, and the relationship between dose and urinary oxalate was
      examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO)
      and serine pyruvate aminotransferase (SPT) activities were measured under the
      conditions of being fed tap water or loading with 0.5% ethylene glycol. In
      addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and
      glycolate increased urinary oxalate concentration in male rats dose-dependently
      but less in female rats. There was almost no change during glycine loading in
      either male or female rats. GO activity was significantly lower in intact female
      and gonadectomized male rats. SPT activity was slightly higher in the female than
      in the male controls. There were no differences in urinary oxalate excretions
      between male and female rats. During ethylene glycol loading, GO and SPT
      activities were similar to those with tap water intake. However, urinary oxalate
      excretion increased to two times the control value in male rats but only slightly
      increased in female rats. CONCLUSIONS: Sex-related differences exist in the
      metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted
      by testosterone. Although difference in GO activity has no physiological effect
      on oxalate synthesis, GO activity affects urinary oxalate excretion during
      ethylene glycol loading. We could also conclude that estrogen decreases GO
      activity in male rats from our results.

PMID- 9915481
TI  - An essential role for nuclear factor kappa B in preventing TNF-alpha-induced cell
      death in prostate cancer cells.
AB  - PURPOSE: Although tumor necrosis factor-alpha (TNF-alpha) induces a strong
      cytotoxic effect on cell growth, many authors have reported that various cancer
      cells are resistant to TNF-alpha and the basis for this sensitivity or resistance
      to TNF-alpha remains to be elucidated. Since nuclear factor kappa B (NF-kappaB)
      activation has recently been reported to inhibit TNF-alpha-induced cell death, we
      studied whether NF-kappaB also assumes a protective role in TNF-alpha-induced
      cell death in prostate cancer cells. MATERIALS AND METHODS: We used two human
      prostate cancer cell lines of DU145 and PC-3. We prepared two different NF-kappaB
      inhibitors, pyrrolidine dithiocarbamate (PDTC) and NF-kappaB decoy. NF-kappaB DNA
      binding activity was detected by electrophoretic mobility shift assay (EMSA).
      Cell survivals were measured by MTT assay. Induction of apoptosis was detected by
      nuclear staining and measured by fragmented DNA ELISA. RESULTS: EMSA showed that
      NF-kappaB inhibitors continuously inhibited TNF-alpha-induced NF-kappaB
      activation. Cell growth was not inhibited by either TNF-alpha (50 ng./ml. or
      less) or NF-kappaB inhibitors. However, both PCA cells treated with TNF-alpha (20
      ng./ml.) plus NF-kappaB inhibitors showed significant growth inhibition compared
      with controls (p<0.05). Nuclei of PCA cells appeared severely fragmented by this
      combination therapy. Furthermore, the levels of DNA fragmentation were
      significantly elevated in PCA cells treated with TNF-alpha (20 ng./ml.) plus NF
      kappaB inhibitors compared with controls (p<0.05). CONCLUSIONS: NF-kappaB
      activation is suggested to produce the resistance of DU145 and PC-3 to TNF-alpha
      and that the combination of TNF-alpha and NF-kappaB inhibitors could be
      constituted an effective therapy to TNF-alpha-resistant human prostate cancer
      cells.

PMID- 9915482
TI  - Expression and possible functional role of the beta3-adrenoceptor in human and
      rat detrusor muscle.
AB  - PURPOSE: To investigate the presence of the beta3-adrenoceptor (beta3-AR) in
      human and rat detrusor muscle and the usefulness of beta3-AR agonists as drugs
      for the treatment of urinary frequency. MATERIALS AND METHODS: FK175, ethyl [(S)
      8-[(R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-6,7,8,9-tetrah ydro-5H
      benzocyclohepton-2-yloxy]acetate monohydrochloride monohydrate, was used as a
      beta3-AR selective agonist. The expression of beta-AR subtypes (beta1-, beta2-,
      beta3-AR) mRNA was investigated in rat and human detrusor muscle by RT-PCR. Beta3
      AR agonist induced cyclic AMP (cAMP) levels were measured in rat detrusor muscle
      strips. The relaxation response produced by a beta3-AR agonist was measured in a
      KCl induced tonic contraction model in rat detrusor muscle strips. The effect of
      a beta3-AR agonist on urinary bladder function was investigated by cystometry
      using a conscious rat model of urinary frequency. RESULTS: beta3-AR mRNA was
      substantially expressed in both rat and human detrusor muscles. The beta3-AR
      agonist, FK175 (10(-7) M), increased the cAMP level by 30% in rat detrusor
      muscle. In isolated rat detrusor muscle strips contracted with KCl, the beta3-AR
      agonist, FK175 (10(-8) to 10(-4) M), produced a concentration-dependent
      relaxation. Moreover, although the relaxation induced with FK175 was blocked by
      the non-selective beta-AR antagonist, bupranolol, it was unaffected by ether the
      beta1-AR selective antagonist, CGP 20712A, or the beta2-AR selective antagonist,
      ICI 118551, suggesting that FK175 induced the relaxation via the beta3-AR.
      Furthermore, in the rat model, the orally administered beta3-AR agonist, FK175
      (10 mg./kg.) significantly increased bladder capacity with no change of
      micturition pressure or threshold pressure. CONCLUSIONS: These results suggest
      that beta3-AR agonists may be effective in the treatment of urinary frequency.

PMID- 9915483
TI  - The effects of castration on relaxation of rat corpus cavernosum smooth muscle in
      vitro.
AB  - PURPOSE: This study was conducted to investigate the role of testosterone (T) in
      regulating the relaxation of isolated rat corpus cavernosum strips in vitro.
      MATERIALS AND METHODS: Male rats were divided into treatment groups of intact,
      castrate, and castrate with T replacement. Norepinephrine (NE) was added to
      contract each of the tissue strips. Next, sodium nitroprusside (SNP), experiment
      I, or 8-Br-cGMP, experiment II, was added to relax the cavernosum tissue. Percent
      relaxations were recorded for each treatment group at each dose level. RESULTS:
      SNP was added to the NE-contracted tissues in doses of 10(-4) and 10(-3) M. In
      this experiment, castration significantly reduced tissue responsiveness to SNP
      and T replacement restored the response to intact levels. In the second
      experiment 8-Br-cGMP was added to the NE-contracted tissues in doses of 10(-5)
      and 10(-4) M. 8-Br-cGMP 10(-4) M was significantly less effective in relaxing
      tissue from castrate animals as compared with intact controls. Again, T treatment
      restored the response to intact levels. CONCLUSIONS: Our results show a clear
      role of T in regulating the ability of corpus cavernosum tissue to relax when
      treated with SNP or 8-Br-cGMP in vitro. In addition, the data suggests that T
      regulates sites distal to the formation of cGMP in the relaxation pathway.

PMID- 9915484
TI  - Glyoxalase I activity in human prostate cancer: a potential marker and importance
      in chemotherapy.
AB  - PURPOSE: To provide information on the activity of Gly-I in prostate cancer.
      MATERIALS AND METHODS: We performed qualitative Gly-I assay on prostate tissues.
      RESULTS: Gly-I activity between prostate cancer and noncancerous specimens
      differed substantially and significantly, although such activity also varied
      somewhat among cancer specimens. CONCLUSIONS: Gly-I activity is indeed higher in
      cancerous than in noncancerous specimens, suggesting that it may play a role in
      prostate cancer homeostasis and survival.

PMID- 9915485
TI  - Dominant role of E-cadherin in the progression of bladder cancer.
AB  - PURPOSE: To elucidate factors with a role in the progression of bladder cancer.
      MATERIALS AND METHODS: One invasive (T24) and two superficial (RT4 and KK47)
      human bladder cancer cell lines, which express metastasis-related genes, were
      used. Cells were intravenously inoculated into chick embryos to evaluate
      metastatic potential to the liver. An orthotopic model with severe combined
      immunodeficiency mice was also used to investigate both histological appearance
      and changes in metastasis-related gene expression. Finally, gene expression
      patterns in a clinical setting were compared between superficial and invasive
      bladder cancers. RESULTS: In culture condition metastasis-related genes,
      including matrix metalloproteinases, urokinase-type plasminogen activator, and
      integrins alpha2 and alpha3 were continually expressed in T24 but only slightly
      or not at all in RT4 and KK47, respectively. The expression pattern of the
      metastasis-related genes in vitro reflected the characteristics of the original
      tumors. Liver metastasis in chick embryos was demonstrated not only with T24
      cells, but also with RT4 cells in which enhanced expression of metastasis-related
      genes was induced. In the orthotopic model, histological appearances were in
      accordance with the characteristics of the original tumors, although enhanced
      gene expression was notable with RT4. Expression of E-cadherin by Western
      blotting was demonstrated only with RT4 under these experimental conditions.
      Furthermore, predominant E-cadherin mRNA expression was found in superficial and
      not in invasive human primary bladder cancers; expression of other genes was
      similar in the two groups. Dominant expression of E-cadherin in superficial
      tumors was confirmed by immunohistochemical analysis. CONCLUSIONS: These results
      implicate loss of E-cadherin expression as a critical factor in facilitating the
      progression of bladder cancer.

PMID- 9915486
TI  - Alteration of the insulin-like growth factor system of mitogens in hyperplastic
      bladders of paraplegic rats.
AB  - PURPOSE: Smooth muscle cells of the bladder retain the ability to proliferate in
      response to injury or mechanical stimulation. Insulin-like growth factor (IGF) I
      is a mitogenic and hypertrophic agent for smooth muscle cells. The purpose of
      this study is to examine if spinal cord injury could lead to bladder hypertrophy
      via the IGF system. MATERIALS AND METHODS: The study involved spinal cord
      transection of female Sprague Dawley rats (approximately 250 to 300 gm.). Six
      weeks following surgery the urinary bladder was collected. Northern and Western
      blotting, and IGF-I receptor (IGF-IR) affinity labeling were used to determine
      the expression of the IGF system, IGFBP levels, and IGF-IR levels respectively.
      RESULTS: Chronic spinal cord injury leads to an increase in the wet weight of the
      bladder and in the level of proliferation cell nuclear antigen expression. IGF-I
      mRNA levels increase, while IGFBP 3 and 5 mRNA and protein levels dramatically
      decrease. The gene expression of IGFBP 2 and 4 varies from rat to rat, and IGF-IR
      expression slightly increases. CONCLUSION: Our results suggest that following
      spinal cord injury, overexpression of IGF-I and underexpression of IGFBP 3 and 5
      may lead to hyperplasia of the smooth muscle layer of the bladder.

PMID- 9915487
TI  - Enhanced continent mechanism of tapered ileum by extramural support from pouch
      abdominal wall: an experimental study in dogs.
AB  - PURPOSE: To construct a reliable continent tube, which is easy to catheterize, we
      created and evaluated a new continent cutaneous diversion using a tapered ileum
      combined with extramural support from the pouch-abdominal wall. MATERIALS AND
      METHODS: Six dogs underwent a procedure in which two ileal segments were tapered
      and anastomosed to the ileal pouch. One of the segments (continent) was placed
      between the back surface of the rectus muscle and the wall of the ileal pouch
      creating a continent tube. The other segment (control) was brought out into the
      abdominal skin directly without any support from the pouch-abdominal wall.
      Urodynamic and radiological studies were carried out postoperatively in all dogs.
      RESULTS: In the continent tubes, the maximum closure pressure with a full pouch
      was significantly higher than those with an empty pouch (p<0.01). The maximum
      closure pressures of the continent tubes were significantly higher than those of
      the control tubes when the pouch was empty (p<0.01). The leak point pressures of
      the continent tubes were significantly higher than those of the control tubes
      (p<0.001). In all dogs, the retrograde radiogram of the continent tubes showed
      perfect canalization without stenosis. CONCLUSION: This study suggests that the
      continent mechanism of tapered ileum can be greatly enhanced by fixing it between
      the abdominal and pouch walls, also allowing easy catheterization in contrast to
      the submucosal tunnel technique.

PMID- 9915488
TI  - WAF1/p21 regulates proliferation, but does not mediate p53-dependent apoptosis in
      urothelial carcinoma cell lines.

PMID- 9915489
TI  - Priapism after transurethral alprostadil.

PMID- 9915490
TI  - Incidence of urinary tract infection in patients without bacteriuria undergoing
      SWL: comparison of stone types.

PMID- 9915491
TI  - Combined treatment of staghorn calculi by fiberoptic transurethral
      nephrolithotripsy and extracorporeal shock wave lithotripsy.

PMID- 9915492
TI  - Array of hope.

PMID- 9915493
TI  - Molecular interactions on microarrays.
AB  - The structural features of nucleic acid probes tethered to a solid support and
      the molecular basis of their interaction with targets in solution have direct
      implication for the hybridization process. We discuss how arrays of
      oligonucleotides provide powerful tools to study the molecular basis of these
      interactions on a scale which is impossible using conventional analysis.

PMID- 9915494
TI  - Expression profiling using cDNA microarrays.
AB  - cDNA microarrays are capable of profiling gene expression patterns of tens of
      thousands of genes in a single experiment. DNA targets, in the form of 3'
      expressed sequence tags (ESTs), are arrayed onto glass slides (or membranes) and
      probed with fluorescent- or radioactively-labelled cDNAs. Here, we review
      technical aspects of cDNA microarrays, including the general principles,
      fabrication of the arrays, target labelling, image analysis and data extraction,
      management and mining.

PMID- 9915495
TI  - Making and reading microarrays.
AB  - There are a variety of options for making microarrays and obtaining microarray
      data. Here, we describe the building and use of two microarray facilities in
      academic settings. In addition to specifying technical detail, we comment on the
      advantages and disadvantages of components and approaches, and provide a protocol
      for hybridization. The fact that we are now making and using microarrays to
      answer biological questions demonstrates that the technology can be implemented
      in a university environment.

PMID- 9915496
TI  - High density synthetic oligonucleotide arrays.
AB  - Experimental genomics involves taking advantage of sequence information to
      investigate and understand the workings of genes, cells and organisms. We have
      developed an approach in which sequence information is used directly to design
      high-density, two-dimensional rays of synthetic oligonucleotides. The GeneChipe
      probe arrays are made using spatially patterned, light-directed combinatorial
      chemical synthesis and contain up to hundreds of thousands of different
      oligonucleotides on a small glass surface. The arrays have been designed and used
      for quantitative and highly parallel measurements of gene expression, to discover
      polymorphic loci and to detect the presence of thousands of alternative alleles.
      Here, we describe the fabrication of the arrays, their design and some specific
      applications to high-throughput genetic and cellular analysis.

PMID- 9915497
TI  - Options available--from start to finish--for obtaining expression data by
      microarray.
AB  - The excitement surrounding microarray technology has been tempered by the limited
      ability of the general biomedical research community to gain access to it. Given
      the hardware required for exploitation of the technology is becoming increasingly
      available, it is an appropriate moment to review options, be they commercially or
      publically available. Here, we provide a snapshot of the rapidly changing field
      of microarray-based RNA expression analysis and consider the components and
      procedures for putting together a complete system.

PMID- 9915498
TI  - Exploring the new world of the genome with DNA microarrays.
AB  - Thousands of genes are being discovered for the first time by sequencing the
      genomes of model organisms, an exhilarating reminder that much of the natural
      world remains to be explored at the molecular level. DNA microarrays provide a
      natural vehicle for this exploration. The model organisms are the first for which
      comprehensive genome-wide surveys of gene expression patterns or function are
      possible. The results can be viewed as maps that reflect the order and logic of
      the genetic program, rather than the physical order of genes on chromosomes.
      Exploration of the genome using DNA microarrays and other genome-scale
      technologies should narrow the gap in our knowledge of gene function and
      molecular biology between the currently-favoured model organisms and other
      species.

PMID- 9915499
TI  - The genetics of cancer--a 3D model.
AB  - Gene expression microarrays hold great promise for studies of human disease
      states. There are significant technical issues specific to utilizing clinical
      tissue samples which have yet to be rigorously addressed and completely overcome.
      Precise, quantitative measurement of gene expression profiles from specific cell
      populations is at hand, offering the scientific community the first comprehensive
      view of the in vivo molecular anatomy of normal cells and their diseased
      counterparts. Here, we propose a model for integrating-in three dimensions
      expression data obtained using the microarray.

PMID- 9915500
TI  - Resequencing and mutational analysis using oligonucleotide microarrays.
AB  - Oligonucleotide microarray (DNA chip)-based hybridization analysis is a promising
      new technology which potentially allows rapid and cost-effective screens for all
      possible mutations and sequence variations in genomic DNA. Here, I review current
      strategies and uses for DNA chip-based resequencing and mutational analysis, the
      underlying principles of experimental designs, and future efforts to improve the
      sensitivity and specificity of chip-based assays.

PMID- 9915501
TI  - DNA microarrays in drug discovery and development.
AB  - DNA microarrays can be used to measure the expression patterns of thousands of
      genes in parallel, generating clues to gene function that can help to identify
      appropriate targets for therapeutic intervention. They can also be used to
      monitor changes in gene expression in response to drug treatments. Here, we
      discuss the different ways in which microarray analysis is likely to affect drug
      discovery.

PMID- 9915502
TI  - Gene expression informatics--it's all in your mine.
AB  - Technologies for whole-genome RNA expression studies are becoming increasingly
      reliable and accessible. However, universal standards to make the data more
      suitable for comparative analysis and for inter-operability with other
      information resources have yet to emerge. Improved access to large electronic
      data sets, reliable and consistent annotation and effective tools for 'data
      mining' are critical. Analysis methods that exploit large data warehouses of gene
      expression experiments will be necessary to realize the full potential of this
      technology.

PMID- 9915503
TI  - Population genetics--making sense out of sequence.
AB  - The complete human genome nucleotide sequence and technologies for assessing
      sequence variation on a genome-scale will prompt comprehensive studies of
      comparative genomic diversity in human populations across the globe. These
      studies, besides rejuvenating population genetics and our interest in how genetic
      variation is created and maintained, will provide the intellectual basis for
      understanding the genetic basis for complex diseases and traits.

PMID- 9915504
TI  - The role of radiology in childhood rhabdomyosarcoma.

PMID- 9915505
TI  - Non-accidental injury: review of the radiology.

PMID- 9915506
TI  - Submental metastases from nasopharyngeal carcinoma.
AB  - The primary treatment for nasopharyngeal carcinoma is radiotherapy. Despite
      optimal treatment the incidence of recurrent persistent or recurrent regional
      disease is significant. It is believed that recurrent regional disease is usually
      associated with local disease. Recurrent nodal disease commonly involves the
      subdigastric and upper jugular region and submental involvement is less common.
      This study includes 25 patients who had palpable submental nodes 2 years or more
      after radiotherapy. Five of the seven patients with proven malignant submental
      nodal recurrence of nasopharyngeal carcinoma had no other evidence of disease.
      Ultrasound accurately identified enlarged nodes and correctly predicted
      involvement. The ultrasound appearances of these nodes and their impact on
      management and prognosis is discussed.

PMID- 9915507
TI  - Metformin and contrast media--a dangerous combination?
AB  - Metformin is a biguanide used to treat type II diabetes mellitus. Since the
      recent introduction of this drug into the United States there has been
      considerable interest in metformin associated lactic acidosis (MALA) following
      intravenous contrast media. The Royal College of Radiologists published advice in
      November, 1996 (Advice to Members and Fellows with regard to metformin-induced
      lactic acidosis and X-ray contrast medium agents, RCR Publication) supporting the
      manufacturers' advice that metformin should not be used in the 48 h before or
      after intravenous (i.v.) contrast medium. We performed a systematic review of the
      literature and this has shown that almost all reported cases of MALA following
      i.v. contrast medium occurred where there was either pre-existing poor renal
      function or another contraindication to metformin usage. There has been only one
      reported case of lactic acidosis following the use of intravenous contrast medium
      in a patient with normal renal function. We suggest that the Royal College of
      Radiologists' advice should be modified and that it is safe to give i.v. contrast
      medium to patients on metformin with normal renal function.

PMID- 9915508
TI  - Detection and significance of splenomegaly on chest radiographs of HIV-infected
      outpatients.
AB  - AIM: The purpose of this study was to determine the prevalence of splenomegaly on
      chest radiographs of HIV-infected outpatients and to correlate with CD4 cell
      counts, opportunistic conditions, liver disease and the presence of intrathoracic
      disease on chest radiographs. METHODS: We reviewed sequential chest radiographs
      of 200 HIV Clinic outpatients at the Jacobi Medical Center, Bronx, New York,
      mixed with chest radiographs of 137 outpatients of unknown HIV status (control
      group) for the presence of splenomegaly and intrathoracic disease. Chest
      radiographic assessment of splenomegaly was correlated with computed tomography
      (CT) or ultrasound (US) in 90 out of 337 patients (27%). Clinical charts of all
      HIV-infected patients were reviewed for CD4 cell count, liver disease and
      opportunistic conditions including those associated with splenomegaly. The HIV
      infected patients were divided into four groups by ascending CD4 cell count:
      Group 1 (0-50 cells/mm3), Group 2 (51-200 cells/mm3), Group 3 (201-500 cells/mm3)
      and Group 4 (>500 cells/ mm3). There were 118 men and 82 women with a mean age of
      40 (range 20-60) years. Mean CD4 was 180 (range 2-1108) cells/mm3. We also
      reviewed all autopsies (n = 239) performed on HIV-infected patients between 1983
      and 1995 at our institution to correlate splenic size with splenic pathology in
      that population. RESULTS: Splenomegaly was present on chest radiographs in 82
      (41%) HIV-infected patients including: 36/84 (43%) Group 1, 23/49 (47%) Group 2,
      18/46 (39%) Group 3, and 5/21 (24%) Group 4 (P = NS). Splenomegaly was present in
      30/97 (31%) patients with no evidence of liver disease or opportunistic
      conditions known to be associated with splenomegaly. Forty-nine HIV-infected
      patients had 63 opportunistic conditions known to be associated with splenomegaly
      (mycobacterial and fungal infections, Kaposi sarcoma and lymphoma), half of whom
      had splenomegaly. Splenomegaly was present on chest radiographs in 18/137 (13%)
      controls. The presence or absence of splenomegaly on CT or US agreed with chest
      radiography in 89%. Among the autopsied patients, 135/239 (56%) had splenomegaly
      (splenic weight > or = 240 g). No specific pathogen was present in 93/135 (69%)
      enlarged spleens. In contrast, one or more opportunistic conditions were present
      in 26/104 (25%) normal weight spleens. CONCLUSION: In conclusion, splenomegaly is
      common in HIV-infected patients and was present in 41% of this series.
      Splenomegaly may be seen in HIV-infected patients without associated
      opportunistic conditions or liver disease and in the absence of specific splenic
      pathology. Chest radiography plays an important role in detecting splenomegaly
      and may lead to earlier diagnosis of HIV infection.

PMID- 9915509
TI  - Spiral CT in acute non-cardiac chest pain.
AB  - AIM: Spiral CT in acute non-cardiac chest pain is usually requested to diagnose
      aortic dissection but a spectrum of other cardiovascular diseases may simulate
      this. The purpose of this study was to assess the impact of spiral computed
      tomography (CT) in patients with suspected aortic dissection and to determine the
      nature and frequency of other disorders simulating it. METHODS: Over a 26-month
      period, all patients undergoing CT for suspected acute aortic dissection were
      recruited. CT was performed using a standard protocol. The CT examinations and
      reports were reviewed along with other relevant imaging, clinical data, surgical
      findings and post-mortem results. The pattern of diagnoses and their associations
      were evaluated. RESULTS: Seventy-six CT examinations were performed on 70
      patients of whom 47 were male. The age of the patients ranged from 24 to 84.
      Seven patients had previously undergone cardiothoracic surgery. Twenty-four
      patients had normal CT findings; 46 patients (66%) had abnormal findings. Seventy
      three significant pathologies were identified including thoracic aortic aneurysm
      (16 cases), aortic dissection (14 cases), acute intramural aortic haematoma (nine
      cases), aortic rupture (eight cases), atherosclerosis (four cases) and
      penetrating atheromatous ulcer (two cases), pulmonary embolus (four cases),
      pericardial disease (12 cases) and complications following surgery (three cases).
      The majority of patients had a life-threatening disease. Five patients without
      dissection had CT findings that explained clinical pulse deficits. CONCLUSION:
      Sudden onset non-cardiac, non-pleuritic chest pain is common to several acute
      cardiovascular disorders. Patients have a high incidence of life-threatening
      disease. Of this group, classic aortic dissection is the most common diagnosis
      but comprises a minority of cases. Spiral CT is a reliable diagnostic test but
      requires conscientious technique for optimum sensitivity and accuracy. Most
      patients will have abnormal CT findings.

PMID- 9915510
TI  - Stenosis in the aorta caused by non-specific aortitis: results of treatment by
      percutaneous stent placement.
AB  - AIM: To evaluate the short-term results of percutaneous stent placement in
      treating stenosis in the aorta caused by non-specific aortitis (Takayasu's
      disease). METHOD: Five patients were treated by this method, all of whom had
      uncontrolled hypertension, haemodynamically significant stenosis in the aorta and
      a clinically inactive disease. Stents were placed to treat an obstructing
      dissection in four and recurrent stenosis in one patient. All procedures were
      carried out via the percutaneous transfemoral route, utilizing self-expanding
      stents. RESULTS: The lesion was located in the thoracic aorta in three patients
      and in the abdominal aorta in two patients. The stenosis decreased from 81+/-2 to
      7+/-3%, the pressure gradient fell from 97+/-5 to 9+/-2 mmHg, the blood pressure
      improved from 200+/-3/124+/-2 to 131+/-2/81+/-2 mmHg, and the drug requirement
      fell from 4+/-.2 to 1.3+/-.3 (P value for all <0.001). No complication was
      encountered. At follow-up at 13+/-4 months, all of the patients had improved
      clinically. Intimal hyperplasia within the stent was seen in two patients who
      underwent follow-up angiograms. CONCLUSION: Percutaneous aortic stenting is
      useful in treating selected patients with non-specific aortitis. Further
      information about the long-term behaviour of intimal hyperplasia and the response
      of stented segments to the aging process needs to be understood before elective
      stenting in this young patient population can be advocated.

PMID- 9915511
TI  - The use of the angio-seal haemostatic puncture closure device in high risk
      patients.
AB  - The use of the Angio-Seal haemostatic puncture closure device in 45 patients
      considered to be at increased risk of puncture site complications is described.
      Successful device deployment occurred in 44 of 50 arteries (88%). Two major
      complications were associated with, but not necessarily caused by, the Angio-Seal
      device. Four minor complications were observed. In a subset of 23 patients well
      enough to mobilize early after their procedure, 17 did so at an average of 2.6 h
      as opposed to the routine 12-18 h for patients after a procedure involving a 6-8F
      sheath. Once the initial learning curve has been overcome, the Angio-Seal device
      is a simple and successful method of achieving arterial haemostasis following
      catheterization and is associated with a low risk of complications. At present we
      would recommend its use for high risk patients only, as manual compression is
      effective in the majority of routine cases.

PMID- 9915512
TI  - Randomized in vitro and in vivo evaluation of different biopsy needles and
      devices for breast biopsy.
AB  - In an experimental study (in vitro and in vivo) we evaluated the efficacy of
      various biopsy needles/devices for breast biopsy. In vitro, biopsies of five
      human cadaveric breast specimens were performed using 33 different
      needles/devices ranging from 14 to 20-gauge. Of these 33 needles/devices, 22
      optimally performing needles were selected for the in vivo study. In the clinical
      part of the study, 44 breast lesions were randomly biopsied with each of the 22
      needles/devices under stereotactic guidance. Tissue specimens were analysed
      quantitatively and qualitatively. Several automatic long-throw guns (Acecut,
      Asap, Biopty, Magnum) obtained greater tissue areas and had a better
      histopathologic score than the conventional type of a side-notch needle like
      Trucut, an aspiration needle like Surecut, or an end-cut needle like Autovac. The
      automatic long-throw guns performed better than the short-throw Monopty gun.
      Regardless of needle size (14-20-gauge), breast biopsies should be routinely
      performed with automated long-throw side-notch guns (Acecut, Asap, Biopty,
      Magnum).

PMID- 9915513
TI  - Optimization of MRI pulse sequences to visualize the normal pars
      interarticularis.
AB  - Magnetic resonance imaging (MRI) is a potentially useful means of detecting acute
      pars stress fractures. However, recent publications have highlighted the
      deficiencies of routine MRI in evaluating the pars interarticularis. Twenty-nine
      volunteers underwent thin section, multi-planar MR examinations of the lumbar
      spine to evaluate whether the normal pars could be more reliably demonstrated.
      MRI examinations were performed with sagittal and reserve angle oblique axial T1W
      images, and also 3D sagittal gradient echo images with reverse angle
      reconstructions. Sagittal STIR images were also acquired in 14 cases. Two hundred
      and ninety pars were evaluated, of which 66% were deemed definitely intact (type
      I) on the sagittal T1W images alone (continuous marrow throughout the pars).
      However 93% were deemed intact when all images were reviewed together. The
      majority of pars defects occur at L4/L5, and 74% of these were intact on the
      sagittal T1W sequence alone, and 90% on combined sequences. Eighteen pars (6%)
      were considered to be hypointense (type II) after review of all sequences, but
      appeared otherwise intact. One volunteer had bilateral definite pars defects
      (type IV) at L5 on all sequences. This study indicates that improved
      visualization of the normal pars interarticularis can be achieved with optimized
      MRI.

PMID- 9915514
TI  - Duodenal intussusception secondary to an internal duodenal duplication.

PMID- 9915515
TI  - Clinical significance of gadolinium-DTPA-enhanced MRI for detection of myocardial
      lesions in a patient with sarcoidosis.

PMID- 9915516
TI  - Congenital arteriovenous malformations arising from the subclavian artery.

PMID- 9915517
TI  - The role of the radiologist in breast diagnosis.

PMID- 9915518
TI  - Trends in the use of pelvic techniques.

PMID- 9915519
TI  - Testicular cancer--who needs surveillance pelvic CT?

PMID- 9915520
TI  - Long-term follow-up of the antheor inferior vena cava filter.

PMID- 9915521
TI  - Occult breast carcinoma presenting as an axillary mass.
AB  - Breast carcinoma presents rarely (<5% of cases) as an axillary mass without an
      obvious primary tumor. The value of mammography in detecting an occult breast
      carcinoma is low, with a sensitivity of 29 per cent and specificity of 73 per
      cent. MRI and positron emission tomography (PET) are potentially more sensitive
      in this setting. We present a case recently seen at the Vanderbilt University
      Hospital, a 63-year-old woman with a 2-cm painless mass in the right axilla.
      Mammography was negative, and fine needle aspiration revealed atypical cells
      suspicious for malignancy. An excisional biopsy of the right axillary lymph node
      revealed metastatic adenocarcinoma, most likely breast primary. A PET showed
      increased uptake of 18-fluorodeoxyglucose and 99m Technetium in the right axilla
      and the right lateral breast. The patient underwent right modified radical
      mastectomy. The final pathological report revealed a 0.9-cm primary tumor in the
      upper inner quadrant of the breast and 1 of 41 nodes positive for tumor. This
      case confirms that mammography has low sensitivity in identifying the primary
      tumor in occult breast carcinoma and illustrates the usefulness of PET in
      identifying the primary tumor. We advocate an aggressive approach to evaluation
      of the breast in women presenting with metastatic adenocarcinoma in the axillary
      nodes. This evaluation should include clinical examination and mammography in all
      cases, and PET and MRI in selected cases. PET and MRI may be particularly useful
      when considering a breast-conserving surgical procedure.

PMID- 9915522
TI  - Leiomyosarcoma of the colon: a second malignant neoplasm after treatment for a
      Wilms' tumor.
AB  - Leiomyosarcoma of the colon is a rare malignancy. We report the case of a 33-year
      old woman with a leiomyosarcoma of the colon occurring as an intussusception 30
      years after receiving abdominal irradiation for a Wilms' tumor. A review of the
      prior and current treatment for Wilms' tumor is discussed, as well as the
      association between second malignancies and abdominal irradiation. Leiomyosarcoma
      of the colon usually presents in the fifth and sixth decades of life and is more
      common in men. The most common symptom is pain. Ninety per cent are diagnosed at
      surgery for treatment of bleeding, perforation, or obstruction. Surgery remains
      the primary treatment. Leiomyosarcomas of the gastrointestinal tract are
      radioresistant, and adjuvant chemotherapy has shown no survival benefit. The
      overall prognosis is poor, with mean 5-year survival of 28 per cent. General
      surgeons need to be aware of the possibility of second malignant neoplasms after
      primary treatment of childhood cancers. Proper reporting is essential to study
      the long-term effects of early treatment of childhood cancers and in predicting
      the best treatment outcomes for these patients.

PMID- 9915523
TI  - Adult colonic intussusception caused by malignant tumor of the transverse colon.
AB  - Adult colonic intussusception is rare and often originates from neoplasms. In
      emergency situations it can be difficult to diagnose. Our aim was to show how the
      integration of readily available diagnostic means in emergency situations can
      help in making a correct diagnosis of this disease. A 68-year old male patient
      presented with vomiting and abdominal pain. The abdomen was distended, with pain
      to palpation in the left quadrants without a mass. Plain radiographs of the
      abdomen showed a large amount of gas in the small bowel and in the right and
      transverse colon. A barium enema demonstrated an endoluminal filling defect in
      the descending colon. Abdominal ultrasonography revealed the presence of
      intraperitoneal fluid and thickened left colonic wall at the site of the lesion,
      with an aspect of a "double ring" consistent with intussusception. A solid
      formation was also revealed at a point distal to the thickened colonic wall. At
      emergency laparotomy an approximately 8-cm-long mass was palpable through the
      left colon. A colostomy was fashioned, and subsequently colonoscopy revealed the
      presence of a left colon tumor. At the subsequent operation an invagination of
      the left transverse colon into the descending colon was confirmed. The left
      transverse and descending colon were resected with high ligation of the left
      colic artery. Macroscopic examination of the invaginating head showed a
      vegetating transverse colon neoplasm. We conclude that in emergency settings the
      association of readily available diagnostic means such as plain abdominal
      radiography, water soluble contrast enema and ultrasonography may yield reliable
      information for diagnosing colonic intussusception.

PMID- 9915524
TI  - Adenocarcinoma of the pancreatic head: a community teaching hospital's experience
      from 1982 to 1992.
AB  - The treatment of adenocarcinoma of the pancreatic head remains variable, with
      multiple therapeutic options including surgery, biliary stenting, chemotherapy,
      and radiation therapy. We retrospectively reviewed our experience from 1982
      through 1992, which included 160 patients with this diagnosis, evaluating their
      treatments and outcomes. There were 66 males and 94 females, with a mean age of
      70+/-11 years. Forty patients (25%) had no surgery; of these, 27 had no further
      treatment, whereas 13 received chemotherapy and/or radiation therapy (CT/RT). Of
      120 patients who had surgical exploration, only 19 (16%) were resectable for a
      potential cure. Eleven of these resected patients had no additional therapy,
      whereas 8 patients received adjuvant CT/RT. Of the 101 unresectable patients, 62
      had no further therapy and 39 received CT/RT. Twenty-two patients (14%) had
      biliary stents placed, 11 in lieu of surgery, 7 preoperatively, and 4
      postoperatively. Perioperative mortality was no different for resectable patients
      (16%) versus unresectable patients (14%). Overall, 90 patients (56%) had one or
      more complications related to their disease or treatment, with no differences
      between groups. Median survivals were as follows: no treatment, 1 month; no
      surgery with CT/RT, 3.5 months; unresectable with no further treatment, 4 months;
      unresectable with CT/RT, 8 months; resection with no additional treatment, 17
      months; and resection with CT/RT, 13 months. Patients with resectable disease had
      a significantly longer survival than patients who had no surgery (P < 0.001) or
      who were unresectable at exploration (P < 0.001); the addition of CT/RT after
      resection had no effect on survival (P = 0.8). The addition of CT/RT
      significantly increased survival for patients who had no surgery (p = .001) and
      for patients who were explored but were unresectable (p = .002). In conclusion,
      despite dismal results, surgery remains the mainstay of treatment for
      adenocarcinoma of the pancreatic head. Although CT/RT did not increase the median
      survival after resection, it doubled the median survival after noncurative
      surgery.

PMID- 9915525
TI  - Intestinal mucosal injury in critically ill surgical patients: preliminary
      observations.
AB  - This was a prospective study designed to evaluate the extent to which intestinal
      mucosal compromise occurs in adult critical care patients with and without
      systemic inflammatory response syndrome (SIRS) and to correlate the degree of
      intestinal injury with outcome. Ten patients from a university hospital surgical
      intensive care unit were identified who manifested SIRS at the time of admission
      to the intensive care unit. Five other critical care patients without SIRS were
      also evaluated. The Acute Physiology and Chronic Health Evaluation II score was
      determined. Intestinal mucosal viability was assessed by serial measurement of
      serum and urine iFABP intestinal fatty acid binding protein (iFABP), a sensitive
      and specific marker for mucosal injury. Outcome in terms of the development of
      multiorgan dysfunction syndrome, adult respiratory distress syndrome, and
      survival was determined. iFABP was detectable in the serum or urine in 8 out of
      10 patients with SIRS. Among the 4 patients with detectable serum iFABP, 2 died
      and 1 developed severe adult respiratory distress syndrome. Nine of 11 patients
      without detectable serum iFABP recovered without major morbidity. iFABP was
      detectable in most patients with SIRS, suggesting that subclinical intestinal
      mucosal compromise is a frequent component of this syndrome. When iFABP was
      detectable, particularly in the serum, the prognosis was poor, even in the
      absence of SIRS, indicating that iFABP may be a relevant and independent
      predictor of outcome in critical care patients.

PMID- 9915526
TI  - Cells isolated from adult human skeletal muscle capable of differentiating into
      multiple mesodermal phenotypes.
AB  - Wound healing is the response of tissue to injury that results in scar formation.
      Tissue regeneration would be a more ideal response. Previously, we have isolated
      a population of cells from avian, rodent, and rabbit skeletal muscle capable of
      differentiating into multiple mesodermal phenotypes. The present experiments were
      designed to determine whether a similar population of cells exist in human
      skeletal muscle. Separate cell preparations from skeletal muscle on an amputated
      leg of a 75-year-old female and the pectoralis muscle of a 27-year-old male were
      enzymatically dissociated and cultured to confluence in Eagle's minimal essential
      medium with 10 per cent preselected horse serum, then trypsinized, filtered, and
      slowly frozen in 7.5 per cent dimethylsulfoxide to -80 degrees C. The cells were
      thawed and plated with the same media plus dexamethasone (a nonspecific
      differentiation agent) at 10(-10) - 10(-6) M concentrations for up to 6 weeks.
      Immunological and histochemical staining assays were performed. Phenotypes
      observed included stem cells with typical stellate morphology (control), skeletal
      myotubes (anti-myosin), smooth muscle (anti-a-actin), bone (von Kossa stain),
      cartilage (Alcec blue), and fat (Sudan black B). These experiments establish the
      existence of a population of mesenchymal stem cells in human skeletal muscle
      capable of differentiating into multiple mesodermal phenotypes. The possibility
      exists of manipulating the mesenchymal stem cells to achieve appropriate
      regeneration of mesenchymal tissues in the injured patient.

PMID- 9915527
TI  - Laparoscopic omental patch repair for perforated duodenal ulcer.
AB  - A retrospective review was carried out on 33 consecutive patients with omental
      patch repair for perforated duodenal ulcer; 13 had laparoscopic repair, and 20
      had open repair. Laparoscopic repair was successful in 12 patients, with only one
      postoperative complication (8%). The morbidity rate for open repair was 15 per
      cent (3 of 20), and there was one postoperative death in the open group (5%).
      Overall, it did not take longer to perform the operation laparoscopically than
      the open method. Patients in the laparoscopic group required less postoperative
      analgesia (mean doses, 0.2 vs 0.9; P = 0.02). There was no difference in terms of
      hospital stay and resumption of diet after operation between the two groups.
      Laparoscopic omental patch repair offers a safe alternative to the open method in
      the treatment of perforated duodenal ulcer.

PMID- 9915528
TI  - Increased efficiency and cost-effectiveness in the evaluation of the blunt
      abdominal trauma patient with the use of ultrasound.
AB  - The efficacy and effectiveness of ultrasound (US) in evaluating patients
      suspected of having blunt abdominal trauma are near that of computed tomography
      (CT) and diagnostic peritoneal lavage (DPL). Because no cost-effectiveness study
      has been reported, the purpose of this study was to demonstrate that US is more
      efficient and cost-effective than CT/DPL in evaluating blunt abdominal trauma.
      Over a 9-month period, 331 patients suspected of sustaining blunt abdominal
      trauma were evaluated at a Level I trauma center by US, CT, and/or DPL. Cost data
      and time to disposition were determined for analysis. The sensitivity,
      specificity, and accuracy of US were similar to those reported in previous
      studies. There was a significant difference in time to disposition with the US
      group being significantly lower (P = 0.001). The total procedural cost was 2.8
      times greater for the CT/DPL group than for the US group. US is not only
      effective in diagnosing blunt abdominal trauma, but it is also more efficient and
      cost-effective than is CT/DPL.

PMID- 9915529
TI  - Abdominal wall endometriomas: report of eight cases.
AB  - Eight cases of abdominal wall endometrioma were encountered in seven patients
      from February 1994 through April 1996. The age of the patients ranged from 19 to
      36 years, with an average age of 32.8 years. Ten abdominal procedures had been
      performed on these patients before the diagnosis of endometrioma: six cesarean
      sections, two diagnostic laparoscopies, one total vaginal hysterectomy, and one
      ventriculoperitoneal shunt. Symptoms occurred from 6 months to 10 years after
      their previous surgery. Only one patient had a prior diagnosis of endometriosis.
      The most common presentation was a cyclic painful abdominal mass. The
      differential diagnosis included endometrioma in four (50%) of the cases.
      Diagnostic tests used for preoperative evaluation included ultrasound, fine
      needle aspiration, and computed tomography. All patients underwent wide local
      excision. There was one recurrence, requiring re-excision at 22 months
      postoperatively. The pathogenesis, diagnosis, treatment, and recent literature
      are discussed.

PMID- 9915530
TI  - Ileoanal pouch procedures: clinical outcomes and quality-of-life assessment.
AB  - Ileoanal pouch (IAP) anastomosis following total colectomy for ulcerative colitis
      or familial adenomatous polyposis is performed with the goal of avoiding a
      permanent ileostomy and its effects on life satisfaction. During a retrospective
      10-year study period, 55 patients underwent IAP construction for ulcerative
      colitis (36) and familial adenomatous polyposis (19). We assessed complications
      by chart review and surveyed patients regarding quality of life via a
      standardized questionnaire. There was no operative mortality, and there were
      three late deaths (6%). Twenty-nine patients (54%) sustained 68 early and late
      complications. Pouchitis was the most common complication (24%), and two patients
      required pouch excision (4%), one for pouchitis and one for rectovaginal fistula.
      Thirty-one patients (65%) have completed questionnaires. Forty-seven patients
      (87%) responded that their overall quality of life is "always" better since
      creation of the IAP, and only one patient in the IAP group has greater than ten
      bowel movements a day. Twenty-one patients (68%) never have interference with
      intimate relationships and 20 (65%) never have interference with physical
      activities. However, 20 patients (65%) sometimes have sleep interference, and 19
      patients (61%) sometimes have fecal soilage. None of the patients continue to
      take steroids. We conclude that the complication rate following IAP construction
      is high, but pouch loss is infrequent. Despite a high complication rate, the
      majority of patients experience an improvement in quality of life.

PMID- 9915531
TI  - An unusual etiology of biliary hilar obstruction and the potential role of acidic
      fibroblast growth factor in the development of a biliary neuroma.
AB  - Neuroma of the biliary tract is a rare condition thought to be caused by trauma
      secondary to cholecystectomy. More rare is the occurrence that causes symptomatic
      biliary obstruction. A 65-year-old woman was hospitalized because of abdominal
      pain, nausea, vomiting, and general malaise of 1 to 2 months duration.
      Cholecystectomy had been performed 40 years before. Ultrasound revealed
      hepatomegaly and dilated intrahepatic ducts. CT showed intra- and extrahepatic
      ductal dilatation with questionable intraductal mass. Endoscopic retrograde
      cholangiopancreatography and percutaneous transhepatic cholangiography
      demonstrated stricture of the hepatic duct bifurcation. The biliary bifurcation
      was resected, and hepaticojejunostomy was performed. The patient's postoperative
      course was unremarkable. Histological examination of the surgical specimen
      revealed positive staining for the S-100 antigen of the obstructing luminal
      stricture (without evidence of cholangiocarcinoma), which was consistent with a
      biliary neuroma. Positive staining was also found for acidic (and not basic)
      fibroblast growth factor (FGF) and two of its high affinity receptors (FGFR-1 and
      FGFR-4). This study supports the apparent association between biliary neuromas
      and cholecystectomy as well as the potential role of an established angiogenic
      and neurogenic growth factor in the formation of this tumor. Finally, this case
      is also unique in that it represents the longest interval between cholecystectomy
      and presentation of a biliary neuroma, 40 years after surgery.

PMID- 9915532
TI  - Prospective, randomized evaluation of early removal of nasogastric tubes in
      postceliotomy trauma patients.
AB  - The objective of this study is to compare early (24-hour) removal of nasogastric
      tubes (NGTs) in trauma patients who have undergone emergency celiotomy to removal
      based on clinical signs of return of bowel function. All trauma patients who
      underwent an emergency celiotomy between November 1994 and August 1997 were
      randomized to 24-hour NGT removal, or removal when flatus and decreased NG output
      indicated. Exclusion criteria included patients with duodenal or esophageal
      injuries, those with airway intubations that were >24 hours, or those who had
      undergone same-hospitalization repeat celiotomy. Gastric or severity of
      intestinal injury were not exclusion criteria. Failure of NGT removal was defined
      as pain, abdominal distention, and vomiting. Mechanisms of injury, Injury
      Severity Score, operative findings, NGT removal times, morbidity, laboratory
      data, and reasons for failure were evaluated. A total of 177 patients qualified
      for the study. Two patients were inappropriately randomized and subsequently
      excluded. Of the remaining 175 patients, 151 sustained penetrating injuries and
      24 sustained blunt injuries. Of the 151 patients in the penetrating injury group,
      68 were randomized to the 24-hour pull (study) group and 83 were randomized to
      the clinical pull (control) group. There were three failures in the study group
      [3 of 68 patients (4.4%)] and three failures in the control group [3 of 83
      patients (3.6%)]. Of the 24 blunt injury patients, 10 were randomized to the
      study group and 14 were randomized to the control group. There was one failure in
      the study group [1 of 10 patients (10.0%)] and one failure in the control group
      [1 of 14 patients (7.1%)]. Overall failure rate for the study group was 5.1 per
      cent [(3+1)/(68+10) = 5.1%] versus 4.1 per cent for the control group. Overall
      failure for all patients in the study was 4.6 per cent. Injury severity score,
      morbidity, and lab values were not significantly different. It is safe to remove
      NGTs at 24 hours in most trauma patients regardless of the severity of injury
      (failure rate, 5.1%). The surgical dogma of the need to have an NGT in longer for
      blunt trauma was not revealed in this study, however, a larger study would be
      needed to determine this with significance.

PMID- 9915534
TI  - Marker clip placement following directional, vacuum-assisted breast biopsy.
AB  - The purpose of this study was to evaluate the accuracy of marker clip placement
      after 11-gauge directional, vacuum-assisted breast biopsies. During a 9-month
      period, 150 stereotactic breast biopsies were performed using a directional,
      vacuum-assisted device and an 11-gauge probe. In 114 cases, a marker clip was
      deployed at the biopsy site using the through-probe method. In 94 cases,
      stereotactic coordinates of the clip were obtained and were available for
      retrospective review. Comparing the coordinates of the lesion with those of the
      clip, placement errors were calculated. Overall, clip placement was within 5 mm
      of the lesion in 81 per cent of cases, within 5-10 mm of the lesion in 17 per
      cent of cases, and >10 mm from the lesion in 2 per cent of cases. Mean total
      placement error was 4.5 mm. The mean z axis error was 3.2 mm, compared with 0.88
      and 2.0 mm for the x and y axes, respectively. Marker clip placement after vacuum
      assisted biopsy is an accurate method of localizing the biopsy site should
      subsequent surgery be required.

PMID- 9915533
TI  - Prevention of postherniorrhaphy urinary retention with prazosin.
AB  - Urinary retention that necessitates catheterization after herniorrhaphy is a well
      known, but usually ignored, situation. Increased sympathetic activity resulting
      from surgery may be the contributing factor. Blockade of alpha receptors in the
      bladder neck and urethral sphincter may prevent postoperative urinary retention.
      In this prospective placebo-controlled study, the efficacy of prazosin in
      preventing postoperative urinary retention after herniorrhaphy was investigated
      in 156 patients. Patients were randomized into two groups. Patients in Group I
      (control) were given placebo orally 12 hours before surgery, just before surgery,
      and 12 and 24 hours after surgery. In Group II, 1 mg of prazosin was given in the
      same manner of placebo. Nine of 84 patients (10.8%) in the prazosin group and 18
      of 72 patients (25%) in the placebo group developed urinary retention.
      Catheterization was required in only 3 patients (3.5%) in the prazosin group
      compared to 10 patients (13.8%) in placebo-treated group (P < 0.05). In
      conclusion, prophylactic use of prazosin after herniorrhaphy significantly
      reduced the incidence of urinary retention and catheterization.

PMID- 9915535
TI  - An open, minimally invasive approach to the lumbar spine.
AB  - A minimum 2-year follow-up retrospective review was undertaken to assess our
      experience with an anterior paramedian muscle-sparing approach to the lumbar
      spine for anterior spinal fusion (ASF). The records of 28 patients (November 1991
      through January 1996) undergoing ASF via a left lower quadrant transverse skin
      incision (6-10 cm) with a paramedian anterior rectus fascial Z-plasty
      retroperitoneal approach were reviewed. Diagnosis, number, and level of lumbar
      interspaces fused, types of fusion, estimated blood loss, length of procedure,
      length of hospital stay, and complications were analyzed. All cases were
      completed as either a same-day anterior/posterior (24 of 28) or as a staged
      procedure at least 1 week after posterior fusion (4 of 28). The General Surgery
      service performed the muscle-sparing approach, whereas the Orthopedic Spine
      service performed the ASF. There were 14 men and 14 women, with a mean age of
      35.5 years (range, 11-52 years). Diagnoses included spondylolisthesis in 20 cases
      (including four grade III or IV slips), segmental instability (degenerative or
      postsurgical) in 7, and 1 flatback deformity. A single level was fused in 20
      cases (L4/5 in 4 and L5/S1 in 16), two levels were fused in 5 cases (L4/5 and
      L5/S1) and three levels were fused in 2 cases (L3/4, L4/5, and L5/S1). The mean
      length of stay was 7.4 days (range, 5-12 days). The mean estimated blood loss was
      300 mL for the anterior procedure alone and 700 ml for both anterior/posterior
      procedures on the same day. The mean length of operating room time for the
      anterior approach and fusion was 117 minutes (range, 60-330 minutes). Posterior
      instrumentation was used in all cases. Anterior interbody struts used included 19
      autogenous tricortical grafts, 4 fresh-frozen allografts (2 femoral rings and 2
      iliac crests), 3 carbon fiber cages packed with autogenous bone, and a Harms
      titanium cage with autograft. There was one L5 corpectomy for which a large
      tricortical allograft strut was utilized. There were no vascular, visceral, or
      urinary tract injuries. In three cases a mild ileus developed, which resolved
      spontaneously. We conclude that the anterior paramedian muscle-sparing
      retroperitoneal approach is safe, uses a small skin incision, avoids cutting
      abdominal wall musculature, and allows for multiple-level anterior spinal fusions
      by a variety of interbody fusion techniques. This approach does not require
      transperitoneal violation or added endoscopic instrumentation, nor does it limit
      fusion level and technique of fusion, as is the case with the recently
      popularized laparoscopic approach to the lumbar spine.

PMID- 9915536
TI  - Is thoracoscopically aided pleural debridement advantageous in children?
AB  - Thoracic empyema encompasses a spectrum of inflammatory manifestations ranging
      from thin parapneumonic pleural effusion to the formation of a thick,
      constricting rind. The aim of this study is to determine the applicability of
      thoracoscopically aided pleural debridement (TAPD) in children with complicated
      empyema and to assess its possible advantages. In the last 6 years, 26 children
      (ages 2 months-16 years; median, 7 years; mean, 7 years) were diagnosed with
      empyema (right, n = 15; left, n = 11). Their charts, radiographs, and follow-up
      courses were reviewed. All children had typical clinical and radiological
      findings of empyema; one also had necrotizing pneumonitis. Treatment modalities
      included antibiotics only (n = 3), antibiotics with tube thoracostomy (n = 11),
      open thoracotomy (n = 5), and TAPD (n = 7). Children treated with antibiotics
      alone had an average (avg) length of stay (LOS) of 31 days. Those managed with
      tube thoracostomy had an avg LOS of 13 days, and those who underwent thoracotomy
      had an avg LOS of 16 days. The seven children treated with TAPD had an avg LOS of
      12 days, and their avg postoperative chest tube use was 6 days. Children with
      TAPD had considerable less pain and recovered faster. TAPD of empyema is
      promising for children whose lungs do not expand promptly after tube thoracostomy
      or who have a persistent loculated empyema.

PMID- 9915537
TI  - Infantile hypertrophic pyloric stenosis: delays in diagnosis and overutilization
      of imaging modalities.
AB  - Infantile Hypertrophic Pyloric Stenosis (IHPS) can usually be diagnosed by the
      detection of a pyloric olive on examination performed by an experience examiner.
      In babies with typical symptoms and a palpable olive, no further confirmation of
      diagnosis is required. We retrospectively reviewed the diagnostic evaluations of
      93 consecutive patients with proven IHPS. Many patients who had the diagnosis
      confirmed on physical examination underwent one or more unnecessary and redundant
      studies. The performance of these studies was associated with delayed diagnosis
      and possibly with adverse clinical health problems. An algorithm for management
      of patients with suspected IHPS is proposed. Prompt examination by an experienced
      examiner is key to the evaluation of such patients.

PMID- 9915538
TI  - Lymphocyte subset analysis for the diagnosis of rejection and infection in
      recipients of liver transplants.
AB  - We retrospectively investigated the predictive value of lymphocyte subset changes
      in the peripheral blood of 37 consecutive liver transplant recipients for
      rejection and infection, both bacterial and cytomegalovirus, during a period of 2
      years. Total lymphocyte count correlated with biopsy-proven rejection. There was
      moderate elevation of CD16+ count during the course of bacterial infection.

PMID- 9915539
TI  - Extraperitoneal rectal perforation due to retroflexion fiberoptic proctoscopy.
AB  - The increasing use of retroflexion proctoscopy to evaluate the distal rectum is
      not without complications. We report a series of three patients who experienced
      extraperitoneal rectal perforation secondary to retroflexion proctoscopy and
      discuss our success with conservative management. By evaluating each clinical
      situation individually and following certain principles, successful outcome can
      be achieved without surgical intervention. Success depends on several factors: 1)
      the injury must be below the peritoneal reflection; 2) the patient must have
      undergone a complete bowel preparation before endoscopy; 3) postinjury, the
      patient must continue to show no evidence of peritonitis or hemodynamic
      instability; and 4) the patient must be given nothing by mouth, started on
      intravenous antibiotics and possibly parenteral nutrition, and closely monitored
      with serial abdominal examinations. The presence of comorbid conditions does not
      necessarily diminish the chance that conservative therapy will succeed.

PMID- 9915540
TI  - Simple sutureless skin graft fixation.
AB  - A simple method to enhance split-thickness skin graft immobilization without
      sutures is described. The method uses collodion to secure a mesh gauze to the
      adjacent skin preventing skin graft dislodgment. The technique is rapid and
      efficient.

PMID- 9915541
TI  - Benign anatomical mistakes: myths or enigmas?

PMID- 9915542
TI  - The use of surgical gloves in the operating room.

PMID- 9915543
TI  - Re: Percutaneous tracheostomy: a cost-effective alternative to standard open
      tracheostomy.

PMID- 9915544
TI  - Re: Abdominal compartment syndrome: prompt recognition and treatment.

PMID- 9915545
TI  - Clinical pathways for general surgeons: laparoscopic Nissen fundoplication.

PMID- 9915546
TI  - Confidentiality.

PMID- 9915547
TI  - Granulocyte transfusion therapy.
AB  - Transfusions of granulocytes have been used for many decades to treat serious
      infections in patients with sustained periods of granulocytopenia. The benefit
      has been limited somewhat by the technical problems of obtaining adequate doses
      of granulocytes from normal donors and by histocompatibility issues in
      alloimmunized recipients. The introduction of granulocyte colony-stimulating
      factor (G-CSF) as a means to induce granulocytosis in donors has rekindled
      interest in this therapy, particularly for the treatment of invasive fungal
      infections. Granulocyte yields after G-CSF stimulation are routinely 3 to 4 times
      higher than have been used in the past and have resulted in posttransfusion
      increments for more than 24 hours after transfusion. Studies in progress should
      help define the utility of these higher dose transfusions in patients with
      infections refractory to antibiotic therapy.

PMID- 9915548
TI  - Recent advances in our understanding of Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome initially was described in 1937 and then again in 1954
      as an X-linked disorder associated with thrombocytopenia, eczema, and recurrent
      infections. It remained mysterious how different cell lineages could be affected
      in this syndrome and, more importantly, how the phenotypic features could be so
      protean. We now know that the features associated with Wiskott-Aldrich syndrome
      include dysfunction of nearly all effector arms of the immune system, as well as
      thrombocytopenia with platelet dysfunction. As a consequence of these
      abnormalities, children and adults with this syndrome have recurrent bleeding,
      recurrent and significant infections with common and opportunistic organisms,
      autoimmune disease, and lymphoreticular malignancies. In 1994, the gene that is
      defective in Wiskott-Aldrich syndrome was identified and found to be a gene with
      limited homology to any known gene families. In the past 4 years, much has been
      learned about the role of this protein in cellular function and T-cell responses
      specifically. This article reviews some recent clinical findings relevant to
      Wiskott-Aldrich syndrome, the proposed cellular role of this molecule, its
      biochemical interactions, and genotype-phenotype considerations.

PMID- 9915549
TI  - Microglia and Alzheimer's disease.
AB  - Microglia play a major role in the cellular response associated with the
      pathological lesions of Alzheimer's disease. As brain-resident macrophages,
      microglia elaborate and operate under several guises that seem reminiscent of
      circulating and tissue monocytes of the leucocyte repertoire. Although microglia
      bear the capacity to synthesize amyloid beta, current evidence is most consistent
      with their phagocytic role. This largely involves the removal of cerebral amyloid
      and possibly the transformation of amyloid beta into fibrils. The phagocytic
      functions also encompass the generation of cytokines, reactive oxygen and
      nitrogen species, and various proteolytic enzymes, events that may exacerbate
      neuronal damage rather than incite outgrowth or repair mechanisms. Microglia do
      not appear to function as true antigen-presenting cells. However, there is
      circumstantial evidence that suggests functional heterogeneity within microglia.
      Pharmacological agents that suppress microglial activation or reduce microglial
      mediated oxidative damage may prove useful strategies to slow the progression of
      Alzheimer's disease.

PMID- 9915550
TI  - Epstein-Barr virus and lymphoproliferative disease.
AB  - The Epstein-Barr virus is a ubiquitous human herpesvirus that is associated with
      an increasing number of human malignancies. Among these are Epstein-Barr virus
      associated lymphoproliferative diseases in immunocompromised patients, a spectrum
      of mainly B-cell diseases that range from polyclonal lymphoproliferative
      diseases, which resolve when immunosuppression is halted, to highly malignant
      lymphomas. Progress has identified Epstein-Barr virus gene products involved in B
      cell transformation, variation in Epstein-Barr virus transforming genes, distinct
      target cell populations with differing regulation of Epstein-Barr virus
      expression, and selective recruitment of other supportive cell types as factors
      in the heterogeneity of lymphoproliferative diseases. New therapeutic approaches
      to treat lymphoproliferative diseases are also being developed. Finally,
      xenotransplantation poses new risks for the introduction of Epstein-Barr virus
      like viruses and more aggressive lymphoproliferative diseases in heavily
      immunosuppressed patients.

PMID- 9915551
TI  - CD5 B cells and B-cell malignancies.
AB  - Over the past year, progress has been made in understanding of the physiology and
      disease associations of CD5+ (B1) B cells, although their exact role in
      pathogenesis remains unclear. Earlier studies on the negative function of CD5
      within the B-cell receptor complex have been substantiated, and it seems likely
      that soon the signaling pathways used by this coreceptor will be elucidated.
      Progress in diagnosis, physiology, and etiopathogenesis of CD5+ malignancies has
      been made, particularly in B-cell chronic lymphocytic leukemia. The low-level
      expression of surface immunoglobulin has been explained by the mutations that
      occur in the associated CD79b. Two new potential tumor-suppressor genes have been
      identified in the hot spot of chromosome 13q, which provides an exciting step
      forward in understanding of the etiopathogenesis of some B-cell chronic
      lymphocytic leukemia. Activated signal transducers for activation of
      transcription factors molecules have been shown to be phosphorylated on different
      amino acids in B1 and chronic lymphocytic leukemia tumors, although the
      significance of this is, as yet, unclear. Finally, aberrant expression of CD40L
      by chronic lymphocytic leukemia T cells may contribute to the immunodeficiency
      that develops in these patients.

PMID- 9915552
TI  - Integrins and signal transduction.
AB  - Integrins are dynamic cell-surface receptors that provide a physical link between
      the extracellular matrix and the cell cytoskeleton. The interaction of integrins
      with extracellular matrix ligands also results in the generation of intracellular
      signals that regulate cell survival and growth, cell differentiation, and cell
      motility. The signaling pathways regulated by integrins are both diverse and
      complex, and involve cross-talk among multiple pathways. An added level of
      complexity resides in the findings that intracellular signals generated by a
      variety of agonists can modulate cell adhesion by regulating integrin-matrix
      interactions. The identification and functional characterization of integrin
      receptor-proximal components involved in this fascinating "inside-out" and
      "outside-in" signal transduction remains an area of intense investigation. This
      review focuses on recent advances in this area.

PMID- 9915553
TI  - Pleiotrophin and midkine, a family of mitogenic and angiogenic heparin-binding
      growth and differentiation factors.
AB  - The heparin-binding polypeptide homologs pleiotrophin and midkine are the only
      known members of a family of secreted growth/differentiation cytokines.
      Pleiotrophin and midkine are both developmentally regulated and highly conserved
      among species. They signal a number of physiological functions involved with
      angiogenesis, neuorogenesis, cell migration, and mesoderm-epithelial
      interactions. Constitutive expression of pleiotrophin and midkine in responsive
      cells support their role as "tumor growth factors" and positive regulators of
      tumor angiogenesis. Widespread deregulation of pleiotrophin and midkine is found
      in many known human cancers or their derived cell lines, and the molecular
      targeting of pleiotrophin to block its signaling in tumor cells has limited tumor
      growth and metastasis in animal models. Elucidating the molecular mechanisms of
      pleiotrophin and midkine action in tumorgenesis and tumor angiogenesis may lead
      to the identification of novel targets for tumor therapy.

PMID- 9915554
TI  - Tyrosine kinases in neutrophils.
AB  - Nonreceptor tyrosine kinases have been shown to represent essential components of
      several signal transduction pathways implicated in neutrophil activation.
      Engagement of phagocytic, cytokine, chemoattractant, and adhesion receptors
      transduces intracellular signals via distinct tyrosine kinases. This article
      discusses the role of distinct tyrosine kinases in mediating neutrophil
      responses.

PMID- 9915555
TI  - Bibliography. Current world literature. Leukocytes.

PMID- 9915556
TI  - Role of risk assessment and bone density monitoring in osteoporosis.
AB  - Osteoporosis and its complications are prevalent medical problems. Of the risk
      factors for fractures, low bone mass is the best predictor. Measuring bone
      density in a person with risk factors for osteoporosis can provide important
      information for both patient and physician when choosing clinical interventions.
      For patients with the disease it is a way to assess response to drug therapy.
      Advances in technology have made measuring bone density safer, faster, and more
      practical than ever. Guidelines addressing when, where, and how the test should
      be done are useful when deciding how to apply this technology to patient care.

PMID- 9915557
TI  - Prevention and treatment of osteoporosis in the elderly.
AB  - Due to age-associated bone losses, all elderly are prone to osteoporosis, which
      often leads to fractures. Fractures frequently result in dependency and
      institutionalization, as well as physical deformities that may lead to
      respiratory and cardiovascular problems. Currently, no drugs exist to promote new
      bone formation. Thus care of the elderly focuses primarily on lifestyle
      modification and increased dietary intake of calcium and vitamin D; decreased
      intake of caffeine, phosphates, and alcohol; smoking cessation; increased
      exercise; and drugs. Drugs for preventing osteoporosis include supplemental
      calcium and vitamin D, hormone replacement therapy, and alendronate. Drugs that
      enhance bone loss or increase the likelihood of falls should be eliminated, if
      possible, or the dosages adjusted. Making residences safer will also help to
      minimize the potential for falls. Drugs for treating osteoporosis include hormone
      replacement therapy, alendronate, and nasal calcitonin. The prevention and
      treatment plan is individualized for each patient, taking into account personal
      preferences, risk factors for osteoporosis and fracture, concomitant diseases and
      drug therapies, efficacy and tolerance of osteoporosis therapy, quality of life,
      life expectancy, finances, and health insurance coverage.

PMID- 9915558
TI  - Management of patients with vertebral compression fractures.
AB  - Osteoporosis is a disease of low bone mass that may not manifest until a patient
      has a fracture. Hip fracture is the most devastating, but vertebral fracture is
      the most common, occurring in 25% of women over 50 years of age and 40% of those
      age 80-85 years. Although 60% of vertebral fractures are clinically silent, they
      are easily diagnosed radiographically. They are associated with height loss,
      deformity, impaired mobility, and pain. Patients should be evaluated for the
      cause of both the fracture and osteoporosis. Therapy includes education about the
      disease, an exercise program, and advice about tailoring routine activities.
      Pharmacotherapy includes annual influenza vaccines, and daily calcium (1200-1500
      mg elemental calcium/day) and vitamin D (400-800 IU/day) supplements. New
      antiresorptive agents alendronate, hormone replacement therapy, and salmon
      calcitonin should be offered to all patients as they reduce fracture rates.

PMID- 9915559
TI  - Origin and migration of luteinizing hormone-releasing hormone neurons in mammals.
AB  - Luteinizing hormone-releasing hormone (LHRH) neurons are unique among
      hypothalamic neurons in that they originate outside of the central nervous
      system. In most vertebrates, LHRH-immunoreactive (-ir) neurons are detected in
      the epithelium of the medial olfactory pit soon after its formation. The LHRH-ir
      neurons migrate out of the placodal epithelium and into the brain along a
      migration route that consists of the central processes of the terminal,
      olfactory, and vomeronasal nerves. LHRH-ir cell migration follows a highly
      ordered course from the initial appearance of the LHRH-ir cells in the epithelium
      of the medial olfactory pit, to the crossing of these cells in cords on the nasal
      septum, to their entrance into the forebrain. Here they separate and follow an
      arching trajectory to their final destinations in the septal and preoptic areas
      and in the hypothalamus. Examination of the molecular makeup of the developing
      migration route reveals the presence of neural cell adhesion molecule (N-CAM) in
      non-LHRH-ir cells. The N-CAM-ir cells migrate into the nasal mesenchyme, trailed
      by N-CAM-ir axons of the olfactory, vomeronasal, and terminal nerves. These N-CAM
      cells and axons link the olfactory epithelia with the developing forebrain and
      together form scaffolding along which the LHRH-ir cells migrate into the brain.
      The focus of this review is on the origin and migration of LHRH-ir neurons in
      mammals, including humans. A discussion of Kallmann's syndrome (hypogonadotropic
      hypogonadism with anosmia) is included, in which there is an absence of LHRH-ir
      in the brain but clusters of LHRH-ir cells in the nasal cavity. This "experiment
      of nature" lends support to the hypothesis that all LHRH-ir cells in humans
      originate in the olfactory placode.

PMID- 9915560
TI  - Synchronized neuronal networks: the GnRH system.
AB  - The anatomical substrate for coordinated release from the dispersed gonadotropin
      releasing hormone (GnRH) neuronal population remains obscure. There is
      physiological evidence that the GnRH hormone itself has a role in tonic
      inhibition or modulation of GnRH function. This has led to the hypothesis that
      there is an ultrashort negative feedback mechanism subserved by axon collaterals
      acting back on the GnRH neurons. Recent ultrastructural studies have revealed
      GnRH synapses on GnRH neurons and their processes. Furthermore, there are
      alterations in the frequency of these synapses with the age and hormonal
      condition of the animal. Another candidate for coordination of neuronal activity
      for which there is some evidence in the magnocellular system, is the gap
      junction. Recently, physiological and anatomical evidence for gap junctional
      modifications among an immortalized GnRH-secreting cell line (GT1) has been
      reported. However, at present there is no immunocytochemical or ultrastructural
      evidence for gap junctions between GnRH neurons. A third and highly unorthodox
      anatomical relationship between (among) these cells has been suggested by serial
      ultrastructural reconstructions of pairs of GnRH neurons in close association. In
      some regions, GnRH neuronal processes can be seen to extend from each member of a
      pair of GnRH neurons. These meet and merge, forming an intercellular bridge. This
      phenomenon has been observed in several pairs of GnRH neurons in rat and monkey.
      The important caveat in making these observations is that techniques employed to
      demonstrate sites of antigenicity can severely compromise the ultrastructural
      integrity of membrane components. For this reason, further verification of the
      existence of intercellular bridges is being pursued. Should their existence be
      confirmed, they would be prime candidates for the coordination of secretory
      events among the scattered GnRH neuronal population.

PMID- 9915561
TI  - Innervation and control of the adenohypophysis by hypothalamic peptidergic
      neurons in teleost fishes: EM immunohistochemical evidence.
AB  - Previous light microscopic studies have revealed neuropeptide-immunoreactive
      neurosecretory fibers in the teleostean neurohypophysis, and ultrastructural work
      has reported direct innervation of endocrine cells by the terminals of fibers
      penetrating the adenohypophysis. This paper reviews our recent data from
      ultrastructural, immunohistochemical, receptor localization, and superfusion
      studies, which suggest a role for neuropeptides in the control of teleost
      pituitary secretion. We have used a combination of pre- and post-embedding
      electron microscopic immunolabeling methods to determine which neuropeptides are
      present in fibers innervating the pituitaries of three species: Poecilia
      latipinna, Dicentrarchus labrax, and Clarias gariepinus. Numerous axon profiles
      with immunoreactivity for the neurosecretory peptides vasotocin and isotocin
      formed large Herring bodies and terminal-like boutons in contact with
      corticotropic, growth hormone, thyrotropic, and pars intermedia cells. Numerous
      melanin-concentrating hormone-immunoreactive fibers and scarcer neurotensin and
      corticotropin-releasing factor-immunoreactive fibers showed similar
      distributions, terminating close to pars intermedia and corticotropic cells.
      Somatostatin, cholecystokinin, galanin, substance P, neuropeptide Y, growth
      hormone-releasing factor, thyrotropin-releasing hormone, and gonadotropin
      releasing hormone-immunoreactivities were found in small calibre fibers
      penetrating among growth hormone, thyrotropic, and gonadotropic cells. These
      morphological findings have been supplemented by autoradiographic studies, which
      showed the distribution of binding sites for vasotocin, isotocin, galanin, and
      neuropeptide Y ligands over specific groups of pituitary cells, and superfusion
      studies that showed growth hormone release was stimulated by growth hormone
      releasing factor and thyrotropin-releasing hormone, but inhibited by
      somatostatin. The implications of these results for neuropeptidergic control of
      teleostean pituitary secretions are discussed.

PMID- 9915562
TI  - Activation and degeneration during aging: a morphometric study of the human
      hypothalamus.
AB  - During the course of aging both activation and degenerative changes are found in
      the human hypothalamus. Degeneration may start around middle-age in some
      neurotransmitter- or neuromodulator-containing neurons. For instance, a decreased
      number of vasoactive intestinal polypeptide (VIP) neurons was observed in the
      suprachiasmatic nucleus (SCN) of middle-aged males. The normal circadian
      fluctuations seen in the number of vasopressin (AVP) neurons in the SCN of young
      subjects diminished in subjects older than 50 years. Moreover, a sharp decline in
      cell number was found in the sexually dimorphic nucleus (SDN) after 50 years in
      males. On the other hand, many hypothalamic systems remain perfectly intact
      during aging like the oxytocin (OXT) neurons in the paraventricular nucleus
      (PVN). The AVP neurons in the PVN are activated during aging as appears from
      their increasing cell number. Also the corticotrophin-releasing hormone (CRH)
      neurons of the PVN are activated in the course of aging, as indicated by their
      increased number and their increased AVP coexpression. Part of the infundibular
      nucleus, the subventricular nucleus, contains hypertrophic neurokinin B neurons
      in postmenopausal women. It can be concluded that a multitude of changes in the
      various hypothalamic nuclei may be the biological basis for many functional
      changes in aging, i.e., both endocrine and central alterations, and that only a
      minority of the possible human hypothalamic changes have so far been studied.

PMID- 9915563
TI  - Efficient cell segmentation tool for confocal microscopy tissue images and
      quantitative evaluation of FISH signals.
AB  - In this paper we have presented a semi-automatic method for segmenting 3-D cell
      nuclei from tissue images obtained using Confocal Laser Scanning Microscope. This
      microscope can focus at different layers of the specimen and hence a stack of
      images giving a 3D representation can be obtained. The existing methods for
      segmenting the cells in 3-D confocal images are highly interactive and, hence,
      time consuming. We have developed an approach, where, given one segmented image
      slice (optical section) of the set of confocal images, the remaining image-slices
      in the image stack can be automatically segmented in a layered approach. One of
      the image-slices in an image stack is considered as a representative image-slice.
      In this image-slice, overlapping boundary pixels are identified interactively
      while the remaining part of the cell boundary is marked using Laplacian of a
      Gaussian operator. This interactively traced portion of the boundary is
      considered as initial boundary for finding the overlapping boundary pixels in the
      neighboring image-slices. Simple basic search strategy is used for boundary
      search in the neighboring image-slices. The method minimizes the human
      interaction and is also found to be efficient and reasonably accurate. Some
      experimental results are presented to illustrate the usefulness of the technique.
      We have also given the application of our segmentation method to quantitative
      evaluation of fluorescence in situ hybridization (FISH) signals. A brief
      comparative study of visual FISH signal evaluation and the FISH signal counting
      by automatic image analysis is also given.

PMID- 9915564
TI  - Impact of demographic distribution and population growth rate on haplotypic
      diversity linked to a disease gene and their consequences for the estimation of
      recombination rate: example of a French Canadian population.
AB  - A disease gene introduced into a rapidly growing population by a single
      individual remains in strong linkage disequilibrium with the surrounding
      molecular markers. Mapping strategies taking advantage of this phenomenon allow
      increased mapping resolution as compared to pedigree analysis. Demographic models
      underlying these strategies usually assume the population exponential growth
      approximated by Poisson distribution of the number of children per individual.
      Knowing the real demographic distribution in the studied French-Canadian
      population, we analyzed the validity of the Poisson approximation. We adapted the
      existing model of the Poisson branching process to the case of a rapidly growing
      population and to non-Poisson distributions. In consequence, we were able to
      apply maximum-likelihood methods to estimate the recombination rate under various
      demographic scenarios. Our analysis shows that the growth rate has a higher
      impact on the estimation of recombination rate than the shape of the demographic
      distribution. The choice of the demographic model (Poisson vs. non-Poisson) has
      little effect on the estimation of the recombination rate but affects the
      expected distribution of haplotype frequencies. This distribution, however,
      depends much more on the population growth rate. Finally, we also demonstrate the
      usefulness of the Luria-Delbruck method, which gives a correct estimation of the
      recombination rate in a growing population, provided the sampling error is taken
      into account in the confidence intervals.

PMID- 9915565
TI  - Designing studies to estimate the penetrance of an identified autosomal dominant
      mutation: cohort, case-control, and genotyped-proband designs.
AB  - One can obtain population-based estimates of the penetrance of a measurable
      mutation from cohort studies, from population-based case-control studies, and
      from genotyped-proband designs (GPD). In a GPD, we assume that representative
      individuals (probands) agree to be genotyped, and one then obtains information on
      the phenotypes of first-degree relatives. We also consider an extension of the
      GPD in which a relative is genotyped (GPDR design). In this paper, we give
      methods and tables for determining sample sizes needed to achieve desired
      precision for penetrance estimates from such studies. We emphasize dichotomous
      phenotypes, but methods for survival data are also given. In an example based on
      the BRCA1 gene and parameters given by Claus et al. [(1991) Am J Hum Genet 48:232
      242], we find that similar large numbers of families need to be studied using the
      cohort, case-control, and GPD designs if the allele frequency is known, though
      the GPDR design requires fewer families, and, if one can study mainly probands
      with disease, the GPD design also requires fewer families. If the allele
      frequency is not known, somewhat larger sample sizes are required. Surprisingly,
      studies with mixtures of families of affected and non-affected probands can
      sometimes be more efficient than studies based exclusively on affected probands
      when the allele frequency is unknown. We discuss the feasibility and validity of
      these designs and point out that GPD and GPDR designs are more susceptible to a
      bias that results when the tendency for an individual to volunteer to be a
      proband or to be a subject in a cohort or case-control study depends on the
      phenotypes of his or her relatives.

PMID- 9915566
TI  - Genetic and environmental contributions to size, color, shape, and other
      characteristics of melanocytic naevi in a sample of adolescent twins.
AB  - The presence of melanocytic naevi is the strongest known risk factor for
      malignant melanoma. We have developed a computer imaging system with which it is
      possible to make quantitative measures of the size, color, and shape of pigmented
      lesions. The objective of this study was to examine the genetic and environmental
      contributions to these characteristics of naevi as measured by computer image
      analysis in a sample of adolescent twins. We captured video images of the 5 most
      atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly
      shaped) on each individual from 322 Australian adolescent twin pairs. Features
      extracted by computer image analysis for each lesion included color, size,
      symmetry, elongation, boundary irregularity, and edge distinctness. We found
      major genetic influences on the color and size of lesions accounting for between
      40 and 80% of total variance. There were significant components of shared
      environmental influence (22-45% of total variance) for the color variables, with
      sun exposure the most obvious explanation. Differences between individuals in
      naevus color and size are largely genetic in origin although there are
      significant environmental contributions to color as well.

PMID- 9915567
TI  - No common major gene for apolipoprotein A-I and HDL3-C levels: evidence from
      bivariate segregation analysis.
AB  - Apolipoprotein A-I (apo A-I) is the most abundant protein in high-density
      lipoprotein (HDL) particles, and it plays an important role in HDL metabolism.
      Both apo A-I and HDL cholesterol (HDL-C) levels are inversely associated with
      risk of cardiovascular disease. Segregation analyses suggest apo A-I levels are
      under the control of one or more major loci. Since HDL particles are
      heterogeneous in their composition and size, genetic influence on its
      subfractions (i.e., HDL2 and HDL3) could vary. A previous report showed evidence
      of a major locus controlling HDL3-C levels in a subset of the current study
      population. Because quantitative trait loci involved in complex diseases are
      likely to have pleiotropic effects on several related traits, it is possible to
      have a common major gene involved in regulating apo A-I and HDL3-C levels. We
      performed a bivariate segregation analysis of apo A-I and HDL3-C levels in 1,006
      individuals from 137 families ascertained through probands undergoing elective,
      diagnostic coronary angiography at the Johns Hopkins Hospital. The results showed
      significant genetic correlation between these two traits, but the hypothesis of a
      common major gene was rejected. Bivariate segregation analysis favored a model
      with two genes controlling apo A-I and a third gene independently controlling
      HDL3-C, and the genetic correlation between these two traits is due to residual
      additive polygenes. Overall, results from this study suggest that there are
      distinct genetic mechanisms for apo A-I and HDL3-C levels. Future studies,
      especially linkage analysis, should consider distinct genetic mechanisms and
      multiple major gene loci.

PMID- 9915568
TI  - Bivariate familial correlation analysis of quantitative traits by use of
      estimating equations: application to a familial analysis of the insulin
      resistance syndrome.
AB  - Familial correlation analysis involving two traits may give a better insight into
      the etiology of multifactorial syndromes than familial analysis focused on single
      traits. Significant cross-trait correlations between biological relatives but not
      between spouses suggest that the two traits share common transmissible factors
      whereas correlations between spouses additionally suggest the influence of shared
      lifestyle factors. We apply the Estimating Equations (EE) technique to the
      estimation of intra-trait and cross-trait familial correlations on two
      quantitative traits. Unlike maximum likelihood methods, the EE method does not
      require one to specify the joint distribution of the traits. Estimation of
      correlations and of their variance involves an iterative three-stage algorithm
      which converges rapidly. The generalized Wald test can be used to test any
      specific hypothesis of familial resemblance. This method has great flexibility
      for handling covariates and incomplete family data. A simulation study indicated
      that the EE technique performed well in large samples (100 families), both in
      terms of type I error and coverage probability . However, in small samples (50
      families), an increase of the type I error and a decrease of the coverage
      probability was observed. As an illustration, we applied this technique to a
      family study of metabolic factors involved in the Insulin Resistance Syndrome
      (body mass index, insulin, triglycerides, HDL-cholesterol, and diastolic blood
      pressure). The study was carried out in a sample of 216 healthy nuclear families
      with > or =2 offspring. The results suggested the existence of a common
      transmissible (genetic or cultural) factor influencing both body mass index and
      insulin, whereas the weak clustering of triglycerides and HDL-cholesterol would
      be more compatible with the influence of shared lifestyle factors.

PMID- 9915569
TI  - Indication of linkage of serum IgE levels to the interleukin-4 gene and exclusion
      of the contribution of the (-590 C to T) interleukin-4 promoter polymorphism to
      IgE variation.
AB  - Previous segregation analysis of a sample of 234 randomly selected Australian
      families showed evidence for a recessive major gene controlling serum
      immunoglobulin E (IgE) levels independently of the specific response to allergens
      (SRA). Since linkage has been recently reported between serum IgE levels and the
      5q candidate region spanning the interleukin-4 (IL-4) gene, we investigated
      whether the recessive major gene detected by segregation analysis was linked to
      the IL-4 region and whether polymorphisms within the IL-4 gene were associated
      with IgE levels. Both sib-pair method and combined segregation and linkage
      analysis using the regressive models were applied to our data. Whereas there was
      no evidence of linkage of total IgE levels to the IL-4 region, an indication of
      linkage (P values ranging between 0.01 and 0.03) was found between IgE levels
      adjusted for SRA and two IL-4 polymorphisms: one dinucleotide repeat in intron 2
      of the IL-4 gene and a single nucleotide (-590 C to T) polymorphism in the IL-4
      promoter. However, the putative IL-4 linked gene did not appear to be in linkage
      disequilibrium with either of these two polymorphisms. A contribution of the IL-4
      promoter polymorphism, presumed to be a potential functional variant influencing
      IgE variation, was also excluded.

PMID- 9915570
TI  - Major genetic effects on airway-parenchymal dysanapsis of the lung: the Humboldt
      family study.
AB  - We examined familial resemblance and performed segregation analysis for the
      maximal expiratory flow rate at 50% of vital capacity (Vmax50) and the ratio of
      Vmax50 to forced vital capacity (FVC), based on data from 309 nuclear families
      with 1,045 individuals in the town of Humboldt, Saskatchewan, in 1993. Vmax50 is
      considered as an index of airway function and Vmax50/FVC is considered as an
      index of airway-parenchymal dysanapsis. Both Vmax50 and Vmax50/FVC were
      preadjusted for host characteristics (age, height, and weight), environmental
      factors, and history of respiratory symptoms and diseases in four separate groups
      (mothers, fathers, daughters, and sons). Both Vmax50 and Vmax50/FVC showed low
      father-mother correlations and significant parent-offspring and sibling-sibling
      correlations. Segregation analysis indicated that for residual Vmax50, the model
      of no-parent-offspring transmission with possible heterogeneity between two
      generations fitted the data as well as did the general model with arbitrary
      transmission probabilities. The Mendelian hypothesis for Vmax50 was rejected,
      which was consistent with our previous findings for other indexes of airway
      function. For residual Vmax50/FVC, however, a single locus explained all the
      familial resemblance and both no-parent-offspring-transmission hypotheses
      [tau(AA) = tau(AB) = tau(BB) = qA and tau(AA) = tau(AB) = tau(BB)] were rejected.
      The study provides evidence for a single locus influencing airway-parenchymal
      dysanapsis.

PMID- 9915571
TI  - Hoxa-10 deficient male mice exhibit abnormal development of the accessory sex
      organs.
AB  - The role of mammalian Hox genes in regulating segmental patterning of axial
      structures and the limb is well established. A similar role in development of
      soft tissue organ systems has recently been suggested by observations linking
      several 5' members of the HoxA and HoxD clusters to segmentation events and
      morphogenesis in the gastrointestinal and genitourinary systems. We have
      specifically examined the role of Hoxa-10 in development of the male accessory
      sex organs by characterizing expression of Hoxa-10 in the developing male
      reproductive tract and correlating expression to morphologic abnormalities in
      knockout mice deficient for Hoxa-10 function. We report that Hoxa-10 expression
      in the Wolffian duct and urogenital sinus is regionally restricted and temporally
      regulated. The domain of expression is defined anteriorly by the caudal
      epididymis and extends posteriorly to the prostatic anlagen of the urogenital
      sinus. Expression was maximal at E18 and down-regulated postnatally, well before
      accessory sex organ morphogenesis is completed. Expression in the prostatic
      anlagen of the urogenital sinus cultured in vitro does not depend upon the
      presence of testosterone. Loss of Hoxa-10 function is associated with diminished
      stromal clefting of the seminal vesicles and decreased size and branching of the
      coagulating gland. The ductal architecture of the coagulating gland was altered
      in approximately 30% of mutants examined and suggests a partial posterior
      morphologic transformation of the coagulating gland. We interpret these data to
      indicate that Hoxa-10 is expressed in a region specific manner during late
      gestation and into the perinatal period and that Hoxa-10 is required for normal
      accessory sex organ development.

PMID- 9915572
TI  - Analysis of a Zebrafish semaphorin reveals potential functions in vivo.
AB  - The semaphorin/collapsin gene family is a large and diverse family encoding both
      secreted and transmembrane proteins, some of which are thought to act as
      repulsive axon guidance molecules. However, the function of most semaphorins is
      still unknown. We have cloned and characterized several semaphorins in the
      zebrafish in order to assess their in vivo function. Zebrafish semaZ2 is
      expressed in a dynamic and restricted pattern during the period of axon outgrowth
      that indicates potential roles in the guidance of several axon pathways. Analysis
      of mutant zebrafish with reduced semaZ2 expression reveals axon pathfinding
      errors that implicate SemaZ2 in normal guidance.

PMID- 9915573
TI  - Restoration of normal bone development by human homologue of collagen type II
      (COL2A1) gene in Col2a1 null mice.
AB  - Development of the vertebrate skeleton is a highly complex process in which
      collagen type II plays a vital role in the formation of long bones via
      endochondral ossification. Collagen type II, which is encoded by a single COL2A1/
      Col2a1 gene, is the most abundant structural protein in the cartilage matrix,
      where it undergoes complex interactions with several other proteins. The sequence
      of mature collagen type II chains, each with about 1,100 amino acids, is
      conserved between different mammalian species. There are 37 amino acid positions
      that are different between mouse and human collagen type II. Previously, we have
      demonstrated that transgenic mice, in which Col2a1 gene is knocked out, exhibit a
      lethal phenotype due to the absence of endochondral bone formation. To
      investigate whether the biological role of collagen type II is conserved between
      the species, human COL2A1 gene was expressed in Col2a1 null mice by crossing with
      transgenic mice in which human COL2A1 gene was integrated. The collagen type II
      from human gene rescued the lethal phenotype in null mice, indicating that the
      biological function of collagen type II is conserved between human and mouse. The
      animals exhibited normal endochondral bone formation and a normal growth plate in
      tibio-tarsal joint. Chondrocytes isolated from the cartilage of these mice
      secreted human protein, suggesting that the animals incorporated heterologous
      protein to form cartilage which is essentially "humanized." The animals reached
      puberty and produced normal progeny. A completely normal phenotype in newborns
      indicates that human COL2A1 gene is expressed properly both temporally and
      spatially. These animals may be useful to generate models to study the effect of
      COL2A1 mutations on skeletal development in humans by introducing mutated gene
      constructs either into embryos or by crossing with transgenic animals with COL2A1
      mutations.

PMID- 9915574
TI  - Hox11-family genes XHox11 and XHox11L2 in xenopus: XHox11L2 expression is
      restricted to a subset of the primary sensory neurons.
AB  - The mouse genome contains a small family of homeobox genes related to Hox11, but
      relatively little is known about the expression of these genes during early
      development. Hox11 itself is expressed in the embryonic spleen, among other
      tissues, and is required for its formation. No description of Hox11L2 expression
      has been presented previously. We have isolated the Xenopus orthologs of Hox11
      and Hox11L2 and have carefully compared their expression patterns during
      embryogenesis. The localization of Xhox11 transcripts in the branchial arches,
      cranial sensory ganglia and spinal cord is similar, but not identical, to that of
      mouse Hox11. Xhox11 expression is not detected in the developing spleen. XHox11L2
      is expressed exclusively in a portion of the primary sensory system in the frog
      embryo, including the cranial sensory ganglia and the Rohon-Beard sensory
      neurons. There is significant overlap in the patterns of Xhox11 and XHox11L2
      expression in the spinal cord and cranial sensory ganglia during early
      development, suggesting that they may function redundantly in these tissues. The
      timing of Xhox11 and Xhox11L2 expression indicates that Hox11-family members may
      participate in the final stages of the differentiation process.

PMID- 9915575
TI  - Tissue specific expression of alternatively spliced murine PECAM-1 isoforms.
AB  - PECAM-1 (CD31) is a cell adhesion molecule that is highly expressed at the sites
      of endothelial cell-cell contact and at lower levels on the surface of platelets
      and leukocytes. It is a member of the immunoglobulin gene superfamily and
      undergoes alternative splicing to generate several isoforms that differ only in
      their cytoplasmic domains. The tissue distribution of the expression of different
      PECAM-1 isoforms has not been previously defined. We have examined PECAM-1
      expression in various mouse tissues and endothelial cells. PECAM-1 mRNA was
      highly expressed in lung, heart, and kidney, and to a lower extent in brain and
      liver. Most endothelial cells in culture expressed high levels of PECAM-1 mRNA;
      however, normal mouse brain endothelial cells rapidly lost PECAM-1 expression in
      culture. To examine the tissue distribution of PECAM-1 isoform expression, RT/PCR
      was performed on the RNA isolated from various mouse tissues and mouse
      endothelial cells. Cloning and sequencing of the cDNA products indicated that
      most tissues and endothelial cells expressed several PECAM-1 isoforms at
      different frequencies. The PECAM-1 isoform that lacks exons 14 and 15 was most
      frequently detected in all cases. A novel PECAM-1 isoform that lacks exons 12 and
      14 was detected in brain. An antibody to the extracellular domain of PECAM-1
      reacted with two major bands, at 130 kDa and 110-120 kDa, in lysates prepared
      from endothelial cells or kidneys at different stages of development. An antibody
      prepared against PECAM-1 exon 14, which reacts only with cytoplasmic domain of
      PECAM-1 isoforms that contain exon 14, failed to react with the major lower
      molecular weight form of PECAM-1 in these lysates. Therefore, PECAM-1 isoforms
      that lack exon 14 are expressed in endothelial cells and tissues in
      developmentally regulated fashion. These results illustrate that multiple PECAM-1
      isoforms are expressed in various mouse tissues and endothelial cells.
      Understanding the distribution of PECAM-1 isoforms, and the identity of
      intracellular proteins with which they may interact, will help to elucidate the
      role of PECAM-1 in endothelial cell-cell interactions and morphogenesis.

PMID- 9915576
TI  - Spatial and temporal changes in chondroitin sulfate distribution in the
      sclerotome play an essential role in the formation of migration patterns of mouse
      neural crest cells.
AB  - We have examined the roles of pertinent extracellular matrix molecules in the
      formation of the neural crest cell migration patterns in the sclerotome of the
      mouse embryo. The present data indicate that permissiveness for migration is
      inversely correlated with chondroitin sulfate content. Experimental removal of
      chondroitin sulfate proteoglycans in the embryo causes neural crest cells to
      migrate even within the posterior half of the somite, which they do not invade
      ordinarily. Moreover, three different sclerotomal regions defined by the presence
      or absence of the ventromedial and/or ventrolateral pathways are present along
      the anteroposterior axis and undergo systematic temporal changes that affect
      migration patterns. The most anterior portion of the sclerotome is conducive to
      both ventromedial and ventrolateral migration (Anterior Region). The intermediate
      portion is conducive to ventromedial migration only (Intermediate Region). No
      neural crest cells are seen within the posterior portion of the sclerotome
      (Posterior Region). At this level, they are observed exclusively in the
      dorsolateral space adjacent to the roof of the neural tube. With advancing
      embryonic development, the rostrocaudal length of the Anterior Region decreases
      and is accompanied by a corresponding enlargement of the Intermediate Region.
      These results suggest that temporal and regional differences in the sclerotome
      contribute to the neural crest cell migration patterns in the mouse. To refine
      our understanding of the underlying mechanisms, regional differences and temporal
      changes in the distribution of extracellular matrix molecules have been examined
      during migration. In the sclerotome, chondroitin sulfate displays distinct
      distribution patterns that are closely correlated with the migration patterns of
      mouse neural crest cells. Furthermore, their migration patterns are altered in
      embryos treated with the inhibitors of chondroitin sulfate proteoglycan
      biosynthesis, sodium chlorate, and beta-D-xyloside. In inhibitor-treated embryos,
      neural crest cell migration occurs even in the posterior portion of the
      sclerotome. The metameric organization of dorsal root ganglia is disturbed in
      these embryos. Our observations provide novel evidence for the importance of
      sclerotomal chondroitin sulfate distribution patterns in mouse crest cell
      migration patterns. We conclude that systematic spatiotemporal changes in the
      distribution of chondroitin sulfate proteoglycans are a key requisite for the
      formation of migration patterns of mouse neural crest cells in the sclerotome.

PMID- 9915577
TI  - Mouse Dac, a novel nuclear factor with homology to Drosophila dachshund shows a
      dynamic expression in the neural crest, the eye, the neocortex, and the limb bud.
AB  - Dac is a novel nuclear factor in mouse and humans that shares homology with
      Drosophila dachshund (dac). Alignment with available sequences defines a
      conserved box of 117 amino acids that shares weak homology with the proto
      oncogene Ski and Sno. Dac expression is found in various neuroectodermal and
      mesenchymal tissues. At early developmental stages Dac is expressed in lateral
      mesoderm and in neural crest cells. In the neural plate/tube Dac expression is
      initially seen in the prosencephalon and gets gradually restricted to the
      presumptive neocortex and the distal portion of the outgrowing optic vesicle.
      Furthermore, Dac transcripts are detected in the mesenchyme underlying the Apical
      Ectodermal Ridge (AER) of the extending limb bud, the dorsal root ganglia and
      chain ganglia, and the mesenchyme of the growing genitalia. Dac expression in the
      Gli 3 mutant extra toes (Xt/Xt) shows little difference compared to the
      expression in wild-type limb buds. In contrast, a significant expansion of Dac
      expression are observed in the anterior mesenchyme of the limb buds of hemimelic
      extra toes (Hx/+) mice. FISH analysis reveals that human DAC maps to chromosome
      13q22.3-23 and further fine-mapping defined a position of the DAC gene at 54cM or
      13q21.1, a locus that associates with mental retardation and skeletal
      abnormalities.

PMID- 9915579
TI  - Hepatocyte growth factor expression in the developing myocardium: evidence for a
      role in the regulation of the mesenchymal cell phenotype and urokinase
      expression.
AB  - During development of the heart, the endocardium of the developing cushion tissue
      transforms into mesenchymal cells that rapidly invade the underlying
      extracellular matrix. This invasive process, along with subsequent proliferation
      and differentiation of the mesenchyme, are essential for the normal formation of
      valvular and septal structures. Several factors have been identified that appear
      to initiate and/or control this transformation process, including the growth
      factor TGF-beta. In these studies we have investigated whether hepatocyte growth
      factor/scatter factor (HGF/SF) may also be involved in some aspects of this
      transformation process. Using an immunohistochemical approach we have detected a
      spatially restricted localization of HGF/SF to the myocardial cells of the
      cushion tissue. HGF was detected in extracts of the developing heart, and the
      presence of the active form correlated with the onset of the transformation
      process and the elevation of urokinase activity. The endocardial-derived
      mesenchymal cells of the cushion tissue were found to express the c-met HGF
      receptor. Isolated endocardial cells responded to the addition of HGF with
      increases in motility, proliferation, and urokinase production. The results from
      these studies suggest that HGF may function as a myocardial-derived mediator of
      the epithelial-mesenchymal transformation by inducing and/or maintaining the
      mesenchymal cell phenotype. The increase in urokinase expression by the cushion
      tissue cells, in response to HGF, may facilitate the invasive abilities of these
      cells and also provide a means of maintaining high levels of active HGF required
      for the stimulation of cell proliferation and migration.

PMID- 9915578
TI  - Epithelial-mesenchymal transformation in the embryonic heart is mediated through
      distinct pertussis toxin-sensitive and TGFbeta signal transduction mechanisms.
AB  - During early development, progenitors of the heart valves and septa are formed by
      epithelial-mesenchymal transformation (EMT) of endothelial cells in the
      atrioventricular (AV) canal. Previously, we showed that pertussis toxin, a
      specific inhibitor of a subset of G proteins, inhibited EMT in chick AV canal
      cultures. This study examines in detail the effects of pertussis toxin on the
      process of EMT. One of the major mediators of EMT is Transforming Growth Factor
      beta 3 (TGFbeta3) which acts through the TGFbeta Type II receptor. To determine
      whether pertussis toxin affects EMT via the TGFbeta Type II receptor pathway, we
      compared AV cultures treated with pertussis toxin and TGFbeta Type II receptor
      blocking antibody. Pertussis toxin inhibited several elements of EMT. At all
      stages tested, pertussis toxin blocked endothelial cell-cell separation, cell
      hypertrophy, and the cellular polarization associated with endothelial
      activation. These activities were unaffected by TGFbeta Type II receptor
      antibodies. Pertussis toxin also reduced transformed mesenchymal cell migration
      by 61%. The expression patterns of several proteins (as markers of EMT) were
      analyzed in untreated, pertussis toxin-treated, and TGFbeta Type II receptor
      blocking antibody-treated cultures. These markers were alpha-smooth muscle actin,
      Mox-1, fibrillin 2, tenascin, cell surface beta 1,4 galactosyltransferase
      (GalTase), and integrin alpha6. Clear differences in marker expression were found
      between the two inhibitors. For example, in all cells, pertussis toxin inhibited
      expression of alpha-smooth muscle actin and GalTase while TGFbeta Type II
      receptor antibody treatment increased expression of these two proteins. These
      data suggest that G protein-mediated signaling is required for several elements
      of EMT. Furthermore, distinct G protein and TGFbeta signal transduction pathways
      mediate discrete components of EMT.

PMID- 9915580
TI  - Vinculin, Talin, Integrin alpha6beta1 and laminin can serve as components of
      attachment complex mediating contraction force transmission from cardiomyocytes
      to extracellular matrix.
AB  - Recently, we reported that cardiomyocytes adhere to extracellular matrix at
      costameres, the striated distribution of vinculin between Z-lines and the
      sarcolemma, where transmission of contraction forces from myofibrils to the
      extracellular matrix occurs. To identify other molecules involved in force
      transmission at costameres, we examined adult rat and embryonic chick
      cardiomyocytes cultured on coverslips or flexible thin silicone rubber substrata.
      Immunolocalization of talin showed a costameric, striated distribution, which
      corresponded to dark contacts with interference reflection microscopy. The
      molecules involved in substrate adhesion were cross-linked with the non
      penetrating cross-linking agent Bis(sulfosuccinimidyl)-suberate and detected by
      immunohistochemical staining with anti-alpha6, alpha3, alphav, or beta1 integrin
      antibodies. Both alpha6 and beta1 showed costameric distributions, but alpha3 and
      alpha(v) did not. The distribution of laminin after cross-linking and extraction
      also showed a costameric distribution. When anti-integrin beta1 antibody was
      added to live cardiomyocytes grown on the silicone rubber substratum, the
      transmission of contraction forces was inhibited. These findings suggest that
      vinculin, talin, integrin alpha6beta1 and laminin system can be involved in
      transmission of contraction force to the extracellular matrix.

PMID- 9915581
TI  - Major role for active extension in the formation of processes by ras-transformed
      fibroblasts.
AB  - Expression of constitutively active Ras protein in fibroblasts results in
      enhanced cell motility, invasion competence and morphological changes including
      the formation of elongate cellular processes. These processes have been shown to
      resemble retraction tails formed passively behind nontransformed cells by
      movement relative to sites of cell-substrate attachment. However, analysis
      presented here reveals that active extension mechanisms also play a role in the
      formation of these processes. Extension of distal process ends occurs at 0.42+/
      0.44 microm/min in ras-transformed fibroblasts and accounts for 63.6+/-27.5% of
      observed process lengths. Active process extension by ras-transformed fibroblasts
      also persists in the presence of cell-cell contacts. Studies conducted using
      actin or microtubule antagonists, and correlation of process behavior followed by
      fixation and immunostaining reveal that process extension requires intact actin
      and microtubule networks. Other analyses reveal that active extension plays a
      significantly smaller role in the formation of processes by non-transformed
      control fibroblasts. These observations demonstrate that constitutively active
      Ras enhances process extension in fibroblasts and is a causal factor in process
      extension by fibroblasts in the presence of cell-cell contacts. Moreover, these
      studies demonstrate that process extension by ras-transformed fibroblasts is
      accomplished through mechanisms similar to those thought to drive active
      extension of processes by other cell types including neurons. These findings
      suggest that extension of cellular processes could play an important role in the
      metastatic behavior of ras-transformed fibroblasts as well as the response of
      untransformed fibroblasts to receptor mediated signal transduction events.

PMID- 9915582
TI  - Cytoplasmic Ca2+ oscillation coordinates the formation of actin filaments in the
      sea urchin eggs activated with phorbol ester.
AB  - Changes in the intracellular Ca2+ concentration ([Ca2+]i) and the formation of
      actin filaments were investigated in unfertilized eggs of the sea urchin
      Hemicentrotus pulcherrimus after activation with a phorbol ester, 12-O
      tetradecanoyl phorbol13-acetate (TPA). Intracellular Ca2+ oscillation was
      observed using a fluorescent Ca2+ indicator dye, calcium green dextran. From
      about 20 to 80 min after the addition of TPA to 100 microM, there was a rise in
      [Ca2+]i, which was followed by Ca2+ oscillation. A change in [Ca2+]i in response
      to TPA was not observed in eggs that had been injected with heparin, an inositol
      1,4,5-triphosphate (IP3) receptor antagonist. Therefore, long-term exposure to a
      high concentration of TPA seems to induce Ca2+ release via the IP3 pathway, as
      well as causing the release of diacylglycerol from membrane lipids. Moreover, the
      elongation of actin filaments occurred in the cytoplasm during the rise in
      [Ca2+]i. Actin filaments also formed when TPA-induced cytoplasmic alkalization
      was inhibited by exposure to Na(+)-free sea water. These results suggest that the
      observed cytoplasmic formation of actin filaments may be related to change in the
      cytoplasmic [Ca2(+)]i, and not intracellular pH, induced by TPA. These phenomena
      may be similar to the changes in actin construction that occur during cell cycle
      events.

PMID- 9915583
TI  - Selective and reversible effects of vinca alkaloids on Trypanosoma cruzi
      epimastigote forms: blockage of cytokinesis without inhibition of the organelle
      duplication.
AB  - Vinca alkaloids, vincristine and vinblastine, produce differential effects on the
      cell division of Trypanosoma cruzi epimastigote forms depending on drug
      concentrations. These effects are related to different microtubule-based
      mechanisms. For 15 microM vinblastine and 50 microM vincristine, the drugs
      inhibit both nuclear division and cytokinesis, and affect cell shape. At 3 microM
      vinblastine and 10 microM vincristine, however, cytokinesis is inhibited without
      major effect on the progression of the cell cycle; this yields giant cells having
      multiple nuclei, kinetoplasts and flagella. Cultures maintained over 1 week with
      daily drug replacement produced cells with more than 16 nuclei and 24
      kinetoplasts, indicating that an equivalent of a fifth cell cycle was initiated.
      The ultrastructure of the multinucleate cells showed a basic organization closely
      similar to that of trypanosomes. Cytokinesis inhibition by vinca alkaloids seems
      to result from modulations of interactions between microtubules and associated
      proteins, rather than from an inhibition of microtubule dynamics as is usually
      proposed for vinca alkaloids. Cytokinesis inhibition is reversible: after
      removing the drug, epimastigotes emerge from the multinucleate cells. The
      emerging process follows a precise axis and polarity which are determined by the
      position of the flagellum/kinetoplast complex. This region could play an
      essential role in cell morphogenesis since zoids (cells without a nucleus) are
      frequently observed.

PMID- 9915584
TI  - Regional regulation of microtubule dynamics in polarized, motile cells.
AB  - Microtubules are known to be required for locomotion of mammalian cells, and
      recent experiments demonstrate that suppression of microtubule dynamic turnover
      reduces the rate of cell motility and induces wandering of growth cones [Liao et
      al., 1995: J Cell Sci. 108:3473-3483; Tanaka et al., 1995: J Cell Biol. 128:139
      155]. To determine how microtubule dynamic instability behavior contributes to
      directed cell locomotion, the behavior of individual microtubules has been
      directly observed and quantified at leading and lateral edges of hepatocyte
      growth factor-treated motile cells. Microtubules extended into newly formed
      protrusions at the leading edge; these "pioneer" microtubules [Waterman-Storer
      and Salmon, 1997: J Cell Biol. 139:417-434] showed persistent growth when
      compared with microtubules in non-leading, lateral edges. The percentage of total
      observation time spent in the growth phase was 68.2% at the leading edge compared
      with 32.0% in non-leading edges, and net microtubule elongation was observed in
      lamellipodia at the leading edge. The frequency of catastrophe transitions was
      threefold greater and the average number of transitions/microtubule/min was
      twofold greater in non-leading edges, as compared with the leading edge. These
      observations demonstrate that pioneer microtubules that enter newly formed
      lamellipodia at the leading edge of motile cells are characterized by persistent
      growth excursions, and directly demonstrate that the frequency of catastrophe
      transitions can be regionally regulated in polarized motile cells. The data
      indicate that region specific differences in the organization and dynamics of
      actin filaments may regulate microtubule dynamic instability behavior in vivo.

PMID- 9915585
TI  - Role for microtubules in centrosome doubling in Chinese hamster ovary cells.
AB  - The centrosome must be replicated once, and only once, during each cell cycle. To
      achieve this somatic cells need to synthesize centrosome proteins, target those
      centrosome proteins to the parental centrosome, and then assemble the centrosome
      subunits into a functional organelle. The mechanisms that underlie each of these
      processes are not known. Studies were performed to investigate whether cellular
      microtubules are involved in centrosome doubling events. For these experiments,
      CHO cells were arrested in either hydroxyurea (HU) alone or in HU plus a
      microtubule inhibitor for 3640 h. The cells then were induced to enter mitosis
      and the numbers of spindle poles/centrosomes were counted following processing of
      the cells for immunofluorescence microscopy using anticentrosome antiserum. These
      studies demonstrated that centrosome replication events occurred in cells
      arrested with either HU alone or HU and taxol while centrosome replication did
      not occur in cells treated with HU and either nocodazole or colcemid. Immunoblot
      analysis determined that centrosome proteins were synthesized in HU/nocodazole
      arrested cells and demonstrated that the role of microtubules in the centrosome
      replication process is not to ensure the synthesis of centrosome subunits.
      Rather, our results suggest that microtubules may be involved in the
      transport/targeting of centrosome subunits to the parental centrosome during
      duplication events. For microtubules to contribute to the transport of centrosome
      subunits during centrosome doubling, centrosome subunits would need to be able to
      bind to microtubules. To test this, co-sedimentation studies were performed and
      it was determined that the centrosome proteins, though overproduced under these
      conditions, remained soluble in HU/nocodazole-treated cells and co-pelleted with
      taxol-stabilized microtubules in the presence of GTP and AMP-PNP. Moreover, co
      sedimentation of one of the centrosome proteins, PCM-1, with microtubules could
      be inhibited by pre-incubation of extracts with antibodies against dynactin.
      Together, these data suggest that during centrosome replication in somatic
      mammalian cells, PCM-1, and perhaps other centrosome components, are targeted to
      the centrosome via transport along microtubules by motor complexes that include
      dynein/dynactin.

PMID- 9915586
TI  - Effect of capping protein, CapZ, on the length of actin filaments and mechanical
      properties of actin filament networks.
AB  - We report on how physiological concentrations of capping protein shorten actin
      filaments and on the remarkably fluid nature of solutions of such short filaments
      even at the high concentrations that exist in cells. We measured the lengths of
      actin filaments formed by spontaneous polymerization of highly purified actin
      monomers by fluorescence microscopy after labeling with rhodamine-phalloidin. The
      length distributions are exponential with a mean of about 7 microm (2600
      subunits). As observed previously with less quantitative assays, copolymerization
      with the actin capping protein, CapZ, reduces the length of the filaments. At
      cellular concentrations of capping protein, one filament forms for each molecule
      of capping protein and the population of filaments is uniformly short. Using CapZ
      to vary the length of actin filaments, we measured how their mechanical
      properties depend on length. The stiffness (elastic modulus) of actin filament
      networks depends steeply on the length, with long filaments contributing far out
      of proportion to their numbers to the stiffness. Even at physiological
      concentrations (300 microM), networks of filaments limited to lengths observed in
      cells with a 1 to 500 molar ratio of CapZ are more fluid and much less elastic
      than lower concentrations of longer actin filaments. Thus the high concentration
      of short actin filaments in cells must be crosslinked to produce the observed
      stiffness of the cortex.

PMID- 9915587
TI  - Effect of 50 Hz sinusoidal electromagnetic field on the kinetics of 14CO2
      exhalation after [14C]-N-nitrosodiethylamine administration in mice.
AB  - N-Nitrosodiethylamine (NDEA) has been identified as a typical environmental
      carcinogen. Its metabolism was studied in mice under the influence of an
      electromagnetic field (EMF). After intraperitoneal administration of [14C]-NDEA,
      0.2 microCi/100 g body weight resulted in 22.8% of the total radioactivity
      exhaled as 14CO2 within 1 h. Mice were exposed to a 50 Hz, 2 mT (rms)
      electromagnetic field, 8 h/day for 8 weeks. There was a significant increase in
      the metabolic turnover of [14C]-NDEA into 14CO2 at the end of both 6 and 8 weeks
      of field exposure, i.e., 26.9% and 37.4% respectively. The enhanced capacity of
      mice to metabolize NDEA after the exposure to EMF may result in animals with a
      smaller amount of the bioactive carcinogen burden, thereby indicating a
      protective role of 2 mT EMF in a whole animal study.

PMID- 9915588
TI  - Experimental determination of hydrogen bandwidth for the ion parametric resonance
      model.
AB  - The ion parametric resonance (IPR) model predicts that distinct patterns of field
      induced biological responses will occur at particular magnetic field combinations
      which establish ion resonances. An important characteristic of resonance is the
      bandwidth response of the system, in part because it determines the required
      tolerances of the test system. Initial development of the IPR model used
      literature data to estimate the bandwidth for any ion resonance to be -/+10% of
      its exact resonance. Because the charge-to-mass ratio of hydrogen is much larger
      than any other biologically significant ion, hydrogen resonance provides a unique
      test case by which a single ionic bandwidth can be clearly measured. Of
      particular relevance is work by Trillo et al. that demonstrated a hydrogen-only,
      resonance-based IPR response of neurite outgrowth in PC-12 cells. The work
      reported here considers the response of nerve-growth-factor-stimulated PC-12
      cells exposed to magnetic fields tuned at or near hydrogen resonance. This work
      was designed to test directly the IPR model hypothesis of a -/+10% ionic
      bandwidth. Consistent with the work of Trillo et al., resonance conditions were
      established using a 2.97 microT static magnetic field, and the AC frequency and
      field strength were varied to prove different aspects of the resonance. With this
      static field 45 Hz was the resonance frequency identified for hydrogen, 42.5 and
      47.5 Hz were near-resonance frequencies, and 40 and 50 Hz bounded the assumed 
      /+10% hydrogen resonance bandwidth. We repeated each test three times. The cell
      responses at 45 Hz exposures agreed with the IPR model predictions and replicated
      results obtained by Trillo et al. Cells exposed to 42.5 and 47.5 Hz (near
      resonance) magnetic fields responded in the same general pattern as those exposed
      to 45 Hz fields, but neurite outgrowth was less than that observed at resonance.
      Measured results for cells exposed to either 40 Hz or 50 Hz fields were
      indistinguishable from off-resonance responses, consistent with the hypothesized
      bandwidth. These results confirm that the response bandwidth for the hydrogen ion
      is no greater than -/+10%, and give further support to the resonance-based
      predictions of the IPR model.

PMID- 9915589
TI  - Design, construction, and validation of a large capacity rodent magnetic field
      exposure laboratory.
AB  - A magnetic field exposure laboratory has been constructed to support National
      Toxicology Program studies for the evaluation of the toxicity and carcinogenicity
      of pure, linearly polarized, 60 Hz magnetic fields in rodents. This dual
      corridor, controlled access facility can support the simultaneous exposure of
      1200 rats and 1200 mice. The facility contains fully redundant electrical and
      environmental control systems and was constructed using non-metallic materials to
      maintain low levels of background (ambient), stray, and cross-talk magnetic
      fields. The exposure module design provides for large uniform exposure volumes
      with good control of stray and cross-talk fields, while allowing the use of roll
      around cage racks for simplified animal husbandry. Stray fields and cross-talk
      have been further reduced by the inclusion of "steering coils" in each exposure
      module. Ambient 60 Hz fields (less cross-talk) in all exposure rooms are <0.1
      microT (1 mG), and static magnetic fields have been mapped extensively. Magnetic
      field strength, waveform, temperature, relative humidity, light intensity, noise
      level, vibration, and air flow in all animal holding areas are tightly regulated,
      and are monitored continuously during all studies. Field uniformity in the animal
      exposure volumes is better than -/+l0%; a systematic program of cage, rack, and
      room rotation controls for possible positional effects within the exposure
      system. Magnetic fields are turned on and off over multiple cycles to prevent the
      induction of transients associated with abrupt field level changes. Total
      harmonic distortion is <3% at all field strengths. The facility has been used to
      study magnetic field bioeffects in rodent model systems in experiments ranging in
      duration from 8 weeks to 2 years.

PMID- 9915590
TI  - Effects of millimeter waves on ionic currents of Lymnaea neurons.
AB  - The effects of mm-waves 60.22-62.22 GHz and 75 GHz on A-type K+ currents and the
      effects of 61.22 GHz on Ca2+ currents of Lymnaea neurons were investigated using
      a whole-cell voltage-clamp technique. The open end of a rectangular waveguide
      covered with a thin Teflon film served as a radiator. Specific absorption rates
      at the waveguide outlet, inserted into physiological solution, were in the range
      of 0-2400 W/kg. Millimeter wave irradiation increased the peak amplitudes,
      activation rates, and inactivation rates of both ion currents. The changes in A
      type K+ current were not dependent on the irradiation frequency. It was shown
      that the changes in the amplitudes and kinetics of both currents resulted from
      the temperature rise produced by irradiation. No additional effects of
      irradiation on A-type K+ current other than thermal were found when tested at the
      phase transition temperature or in the presence of ethanol. Ethanol reduced the
      thermal effect of irradiation. Millimeter waves had no effect on the steady-state
      activation and inactivation curves, suggesting that the membrane surface charge
      and binding of calcium ions to the membrane in the area of channel locations did
      not change.

PMID- 9915591
TI  - Electrochemical treatment of human KB cells in vitro.
AB  - Electrochemical treatment (ECT) of cancer is a promising new method by which
      direct current is delivered into tumor tissue to induce tumor regression. The
      purpose of this study is to evaluate the effectiveness of ECT on human cancer
      cells and to investigate the factors that affect ECT. The biological mechanisms
      of ECT in cancer treatment were also explored. Using human KB cells, ECT was
      found to delay cell growth by using 0.3 coulombs (C)/ml (1.5 C in 5 ml of culture
      medium; 3 V, 400 microA for 62.5 min). From the results of a colony-forming
      assay, it was clearly demonstrated that increasing the ECT dose decreases tumor
      cell survival. A cytotoxicity study, in which a methylene blue assay was used,
      determined that, for 2.5 x 10(5) cells in culture, the 1D50 was 0.68 C/ml. For a
      fixed dose of 0.6 C/ml (3 C in 5 ml), using higher current and shorter treatment
      time resulted in better cell survival. Time, therefore, is an important factor.
      When cell concentration was altered, the survival was higher for increased cell
      concentrations. A thymidine incorporation assay indicated that the amount of
      [3H]thymidine incorporated into DNA decreased as the ECT dose increased. After
      treatment with 1 C/ml (5 C in 5 ml; 3 V, 400 microA for 208.4 min), pH at the
      anode decreased to 4.53 and at the cathode increased to 10.46. These results
      indicate that ECT is effective for killing human KB cells in vitro and that the
      toxicity effect is related to charge, current, and treatment time. The effect of
      pH alteration on cells is one of the mechanisms of ECT.

PMID- 9915592
TI  - Dosimetry in mice exposed to 1.6 GHz microwaves in a carrousel irradiator.
AB  - We have developed a carrousel irradiator for mice which delivers a head-first and
      near-field radiofrequency exposure that more closely simulates cellular telephone
      and radio use than conventional whole body exposure systems. Mouse cadavers were
      placed on the carrousel irradiator and exposed with their noses 5 mm from the
      feedpoint of a 1.6 GHz antenna. Local measured specific absorption rates (SAR) in
      brain regions corresponding to the frontal cortex, medial caudate putamen, and
      midhippocampal areas were 2.9, 2.4, and 2.2 W/kg per watt of irradiated power,
      respectively. In addition, average SAR was estimated to be 3.4 W/kg per watt
      along the sagittal plane of the brain, 2.0 W/kg per watt along the sagittal plane
      of the body, and between 6.8 and 8.1 W/kg per watt at peak locations along the
      sagittal plane at the body surface. This detailed SAR information in mice is
      critical to the interpretation of biological studies of IRIDIUM exposure, and
      similar analysis should be included for all studies of in vivo exposure of small
      animals to microwaves.

PMID- 9915593
TI  - Clinical progression of transplanted large granular lymphocytic leukemia in
      Fischer 344 rats exposed to 60 Hz magnetic fields.
AB  - The purpose of this study was to determine if 60 Hz magnetic fields can alter the
      clinical progression of leukemia in an animal model. Large granular lymphocytic
      (LGL) leukemia cells from spleens of leukemic rats were transplanted into young
      male Fischer 344 rats, producing signs of leukemia in approximately 2-3 months.
      The animals were randomly assigned to 4 treatment groups (108/group) as follows:
      1) 10 G (1.0 mT) linearly polarized 60 Hz magnetic fields, 2) sham exposed [null
      energized unit with residual 20 mG (2 microT) fields], 3) ambient controls [<1 mG
      (0.1 [microT)], and 4) positive controls (a single 5 Gy whole body exposure to
      60Co 4 days prior to initiation of exposure). All rats were injected
      intraperitoneally (ip) with 2.2 x 10(7) LGL leukemic cells at the initiation of
      exposure or sham exposure. The magnetic fields were activated for 20 h/day, 7
      days/week, allowing time for animal care. The experimental fields were in
      addition to natural ambient magnetic fields. Eighteen rats from each treatment
      group were bled, killed, and evaluated at 5, 6, 7, 8, 9, and 11 weeks of
      exposure. Peripheral blood hematological endpoints, changes in spleen growth, and
      LGL cell infiltration into the spleen and liver were measured to evaluate the
      leukemia progression. No significant or consistent differences were detected
      between the magnetic field exposed groups and the ambient control group, although
      the clinical progress of leukemia was enhanced in the positive control animals.
      These data indicate that exposure to sinusoidal, linearly polarized 60 Hz, 10 G
      magnetic fields did not significantly alter the clinical progression of LGL
      leukemia. Furthermore, the data are in general agreement with previous results of
      a companion repeated-bleeding study in which animals were exposed for 18 weeks.

PMID- 9915594
TI  - Effects of low-level 50 Hz magnetic fields on the level of host defense and on
      spleen colony formation.
AB  - The results of 3 sets of experiments on the effects of 22 microT sinusoidal 50 Hz
      magnetic fields (MF), applied for 1 h on 5 successive days (1 h/5 days), on the
      level of host defense and on spleen colony formation are reported. The first set
      of experiments shows the effects on the number of colony-forming units (CFUs) on
      the spleen and on the cellularity of the thymus in mice. The MF exposures
      resulted in an increase in CFUs which was statistically significant with respect
      to the controls, but not with respect to the shams. Statistically significant
      changes in the thymic weight and thymic index with respect to both the controls
      and the shams were measured 1 h after the last MF exposure. In the second set of
      experiments, the mice were given a sublethal dose of X-rays (6 Gy), which was
      followed by exposure 2 h later to the MF. The MF exposure was repeated at the
      same time of day for 5 days. The number of colonies per spleen showed a
      consistent, statistically significant increase with MF exposure and the number of
      CFUs per femur was decreased. In the third set of experiments, bone marrow was
      taken from mice which had been exposed to 22 microT fields and injected into mice
      which had been exposed to a lethal dose of X-rays (9 Gy). The number of CFUs per
      femur in the recipient mice was shown to be reduced by a statistically
      significant amount at 1 and 4 days after injection.

PMID- 9915595
TI  - In vitro excitatory actions of corticotropin-releasing factor on rat colonic
      motility.
AB  - Corticotropin-releasing factor (CRF) has been shown to affect gastrointestinal
      functions, however, a direct effect of CRF on the intestine has not been
      demonstrated. To determine the direct effect of CRF and its antagonist alpha
      helical-CRF9-41 (alpha-h-CRF) on the enteric nervous system, we studied the
      action of these substances on electrical and mechanical parameters of peristaltic
      activity on isolated distal colon of the rat. The effects of CRF were evaluated
      in vitro on rat isolated colonic segments in which intraluminal pressure,
      longitudinal displacement, ejected fluid volume and extracellular electrical
      activity were simultaneously recorded during colonic peristaltic reflex. The
      addition of CRF (10(-10) - 10(-8) M) to the bath fluid provoked a concentration
      dependent increase of both mechanical and electrical peristaltic activity. The
      CRF-receptor antagonist alpha-h-CRF dose-dependently (10(-10) - 10(-7) M) induced
      a decrease of the colonic mechanical and electrical activity and prevented (10(
      8) - 10(-6) M) CRF (10(-8) M) maximal effects. These results indicate: (a) CRF
      can exert its effects on colon functions by a direct action, (b) a specific CRF
      receptor is present in the rat colon. Indeed, CRF effects are antagonized by the
      specific CRF antagonist alpha-h-CRF, (c) the fact the alpha-h-CRF displays an
      activity on its own reveals that colonic functions are controlled by an
      endogenous CRF tonic activity.

PMID- 9915596
TI  - Effects of suramin on electrical and mechanical activities in antrum smooth
      muscle of the guinea-pig stomach.
AB  - The effects of suramin on electrical and mechanical responses produced by
      adenosine triphosphate (ATP), acetylcholine and transmural nerve stimulation were
      observed in antrum smooth muscle isolated from the guinea-pig stomach. Suramin
      (>10(-6) M) inhibited the non-adrenergic non-cholinergic inhibitory junction
      potential, with no alteration of the resting membrane potential, slow wave and
      the ATP-induced responses (hyperpolarization and inhibition of slow waves). The
      amplitude, but not the frequency, of spontaneous rhythmic contraction was
      inhibited by suramin (>10(-5) M), with no alteration of electrical responses of
      the membrane. Transmural nerve stimulation elicited cholinergic excitatory and
      non-adrenergic non-cholinergic inhibitory responses on the spontaneous
      contraction, and suramin inhibited only the latter. Suramin did not alter the ATP
      induced inhibition of spontaneous contraction. The contractions produced by low
      concentrations (<10(-7) M), but not high concentrations (10(-6) - 10(-5) M), of
      acetylcholine were inhibited by suramin. It is concluded that in smooth muscle of
      the guinea-pig antrum, suramin inhibits contractions produced spontaneously and
      by low concentrations of acetylcholine, with no relation to the electrical
      responses of the membrane. Parallel inhibition by suramin of the electrical and
      mechanical responses elicited by excitation of non-adrenergic non-cholinergic
      inhibitory nerves may not be causally related to the inhibition of ATP-receptors.

PMID- 9915597
TI  - Transmitter release and uptake evoked by the amphibian skin alkaloid,
      pumiliotoxin-B (PTX-B), in the electrically stimulated mouse vas deferens
      preparation (MVD).
AB  - Upon electrical stimulation three transmitters are known to be released from the
      adrenergic nerve terminals of the isolated MVD preparation: two motor
      transmitters (noradrenaline (NA) and ATP) acting synergistically to provoke
      twitch contraction, and an inhibitory transmitter, the peptide NPY. The frog
      alkaloid pumiliotoxin-B (PTX-B) displayed two opposite effects on the
      electrically stimulated MVD: at low concentrations (0.1-0.3 microM) it caused
      twitch depression, at higher concentrations (0.5-2 microM) there was a potent
      twitch stimulation. Transmitters and/or receptors involved in the depressive
      effect could not be clearly identified, although interference with NPY is
      possible. On the other hand, the potent twitch stimulation caused by PTX-B may be
      due to exaggerated release of the same transmitters (NA and ATP) involved in
      twitch stimulation produced by electrical stimulation. Opening by PTX-B of the
      Na+ channels on the membrane of the adrenergic nerve terminals causes activation
      of the amine pump facilitating re-uptake of not only endogenous NA but also of
      exogenous catecholamines.

PMID- 9915598
TI  - Pharmacological analysis of the double peaked vasoconstrictor responses to
      periarterial electric stimulation.
AB  - Vasoconstrictor responses to periarterial nerve stimulation were studied with the
      use of prazosin (an alpha1-adrenoceptor antagonist) and alpha,beta-methylene ATP
      (a P2X receptor desensitizer) in canine isolated, perfused splenic arterial
      preparations. Double peaked responses (two phases of the constriction) were
      readily induced with the conditions of 30 s trains of pulses at 10 V amplitude, 1
      ms duration in a frequency-related manner. At low frequencies (1-3 Hz), the 1st
      phase might contain only a purinergic component which was mostly inhibited by
      treatment with alpha,beta-methylene ATP. At high frequencies (4-10 Hz), the 1st
      phase was in part inhibited by prazosin and the remaining component of this phase
      was abolished by alpha,beta-methylene ATP. The 2nd phase response was markedly
      inhibited by prazosin, and remaining component of this phase was abolished by
      alpha,beta-methylene ATP at all frequencies used. It is concluded that (1) the
      1st phase is probably induced via an activation of P2X receptors at low
      frequencies, and at high frequencies via both P2X and alpha1-adrenoceptors, and
      (2) the 2nd phase probably involves mostly alpha1-adrenoceptors and partially P2X
      receptors.

PMID- 9915599
TI  - Pharmacology of neurotransmission to the smooth muscle of the rat and the guinea
      pig prostate glands.
AB  - Histochemical studies carried out on sections of rat and guinea-pig prostate
      glands revealed the presence of acetylcholinesterase- and noradrenaline
      containing nerve fibres in the fibromuscular stroma. Positive staining for
      acetylcholinesterase but not for noradrenaline was also seen in the epithelium.
      Electrical field stimulation with trains of 0.5 ms pulses, dial setting of 60 V,
      delivered at 1-30 Hz for 10 s at 5 min intervals, was applied to nerve terminals
      within the rat and guinea-pig isolated prostate glands. The evoked contractions
      were frequency-dependent. Tetrodotoxin (1 microM) abolished contractions evoked
      by short pulse repetitive stimulation (trains of 20 0.5 ms pulses at 10 Hz every
      100 s) in tissues from both species. The field stimulation-induced contractions
      of the prostatic smooth muscle were markedly attenuated by guanethidine (10
      microM) and prazosin (0.1 and 1 microM) indicating that neurotransmission to the
      prostatic smooth muscle in both species is predominantly sympathetic and
      noradrenergic, and that noradrenaline released during field stimulation acts at
      postjunctional alpha1-adrenoceptors. Atropine (0.1 and 1 microM) caused a slight
      but significant reduction of the field stimulation-induced contractions of
      prostate smooth muscle from both the rat and the guinea-pig. In the guinea-pig,
      cholinesterase inhibition by physostigmine and neostigmine, both at 10 microM,
      enhanced the field stimulation-induced contractions of the prostatic smooth
      muscle. This enhancement was reversed by atropine (0.1 microM) but not by
      hexamethonium (0.1 mM). These data are compatible with some participation of
      acetylcholine, acting at muscarinic receptors, in neurotransmission to prostatic
      smooth muscle.

PMID- 9915600
TI  - Cardiovascular actions of nitric oxide synthase inhibition in the portal
      hypertensive rat.
AB  - We have investigated the actions of the nitric oxide synthase inhibitor L-NMMA in
      the portal hypertensive Wistar rat in vivo. Resting blood pressure in the
      anaesthetised portal hypertensive rat was 107.8+/-11.0 / 79.2+/-11.7 mmHg (n =
      12), which was significantly lower than in sham-operated animals (143.0+/-3.8 /
      114.0+/-4.0 mmHg, n = 19; P < 0.01). Cardiac output was significantly higher in
      portal hypertensive (30.2+/-1.0 ml min(-1) per 100 g, n = 12) than sham-operated
      animals (23.7+/-2.2 ml min(-1) per 100 g, n = 13; P < 0.01). Intravenous
      injection of L-NMMA (10 mg kg(-1)) significantly increased systemic blood
      pressure in both portal hypertensive and sham-operated animals to 123.0+/-15.0 /
      93.4+/-14.0 mmHg and 162.1+/-5.7 / 131.6+/-6.0 mmHg, respectively. The magnitude
      of the changes were similar in both groups. This increase in blood pressure was
      accompanied by a decrease in cardiac output to 88.5+/-2.8% and 91.5+/-2.4% of
      control in portal hypertensive and sham-operated animals, respectively (no
      significant difference). L-NMMA (10 mg kg(-1)) had similar effects on small
      mesenteric arterial conductance in both portal hypertensive and sham operated
      animals, reducing conductance to 84.4+/-3.6% (n = 6) and 82.7+/-1.2% (n = 4) of
      control, respectively. It is concluded that L-NMMA has similar effects in vivo in
      portal hypertensive as compared with sham-operated rats. Hence, an enhancement of
      endothelium-derived nitric oxide is not involved in the hyperdynamic state
      following portal hypertension in the rat.

PMID- 9915601
TI  - Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated
      with isoniazid.
AB  - High doses of isoniazid increase hypotension induced by vasodilators and change
      the accompanying reflex tachycardia to bradycardia, an interaction attributed to
      decreased synthesis of brain gamma-aminobutyric acid (GABA). In the present
      study, the possible enhancement by isoniazid of bradycardia induced by beta
      adrenoceptor antagonists was determined in rats anaesthetised with chloralose
      urethane. Isoniazid significantly increased bradycardia after propranolol,
      pindolol, labetalol and atenolol, as well as after clonidine, but not after
      hexamethonium or carbachol. Enhancement was not observed in rats pretreated with
      methylatropine or previously vagotomised. These results are compatible with
      interference by isoniazid with GABAergic inhibition of cardiac parasympathetic
      tone. Such interference could be exerted centrally, possibly at the nucleus
      ambiguus, or peripherally at the sinus node.

PMID- 9915602
TI  - Effects of U-50,488H on isolated atria from rats chronically treated with the
      kappa-opioid agonist, U-50,488H.
AB  - The present investigation was aimed at determining if chronic activation of kappa
      or mu-opioid receptors induce development of tolerance and dependence to kappa
      opioid agonists on the isolated left atria of the rat. Tolerance to a kappa
      agonist (specific tolerance) was induced by chronic administration of U-50,488H,
      a selective kappa-agonist (15 mg kg(-1) i.p. twice a day for 4 days). The animals
      were rendered tolerant to morphine by subcutaneous implantation of morphine
      pellets (75 mg per pellet) for 7 days. Tolerance to U-50,488H was observed after
      its chronic administration and was revealed as a rightward shift of the
      concentration-response curve, it was accompanied by a decrease in the maximum
      response and in the slope. Preparations from morphine-treated rats were not
      tolerant to the selective kappa-agonist, that is, there was no cross-tolerance
      between mu- and kappa-agonists. Dependence to the kappa-agonist was tested by
      administration in the organ bath of Mr-2266 (preferential kappa-antagonist) or
      nor-binaltorphimine (nor-BNI; selective kappa-antagonist). The administration in
      the organ bath of the kappa-antagonists Mr-2266 or nor-BNI to preparations from U
      50,488H-treated rats induced an increase in atrial force of contraction. In
      contrast, the administration of the kappa-antagonists to preparations from
      control rats induced a decrease in atrial force of contraction. These findings
      demonstrate that left atria from chronically U-50488H-treated rats exhibit
      tolerance to the negative inotropic effects of U-50,488H as well as opioid
      withdrawal after nor-BNI.

PMID- 9915603
TI  - The emerging importance of genetics in epidemiologic research. I. Basic concepts
      in human genetics and laboratory technology.
AB  - PURPOSE: To define a general framework of current approaches to the discovery of
      disease-associated genes and the role of genetic factors in influencing disease
      risk through the integration of genome technology and traditional epidemiologic
      methods. METHODS: An overview of basic concepts in human genetics, laboratory
      methodology for measuring genetic variation believed to influence common
      diseases, and issues concerning preparation and utilization of genetic materials
      is provided as a foundation for genetic epidemiologic research. RESULTS:
      Identification and characterization of human genetic variation is providing new
      risk factors for disease in the form of DNA sequence variation. The availability
      of genetic material from participants in large epidemiologic studies and
      appropriate informed consent represents an invaluable resource for exploring
      genetic and environmental influences on disease risk. CONCLUSIONS: Advances in
      genome technology coupled with vast amounts of genetic data resulting from the
      Human Genome Project are broadening the scope of epidemiologic research and
      providing tools to identify individuals at increased risk of disease. Combining
      diverse expertise from the fields of epidemiology and human genetics provides
      unique opportunities to localize disease-susceptibility genes and examine
      molecular mechanisms of complex disease etiology.

PMID- 9915604
TI  - More research is needed.

PMID- 9915605
TI  - Establishing research priorities in etiologic epidemiology.
AB  - PURPOSE: A major goal of epidemiology is to discover the causes of disease in
      populations. The aim of this study was to develop a method for establishing
      research priorities within this very broad area of scientific inquiry. METHODS:
      While the approach is applicable to many diseases, cancer was used here, in part
      because of its importance to both individuals and governments. Measures of
      disease were estimated from data in the Ontario Cancer Registry, and combined to
      yield a single assessment of impact for each cancer site. Measures of exposure
      prevalence were identified from recent population health surveys. Cross
      classification by disease and exposure rankings yielded a matrix of scores of
      "relative importance" for each cancer-exposure combination. Onto this matrix was
      overlaid: 1) estimates of statistical power for examining each association; 2)
      biological plausibility of each association; and 3) strength of the
      epidemiological evidence supporting each association. RESULTS: The disease
      exposure matrix, viewed in light of statistical power, biological plausibility,
      and current epidemiological evidence, yielded, in the examples shown, some
      potentially interesting yet understudied associations (e.g., non-Hodgkin lymphoma
      (NHL) and certain aspects of dietary intake). CONCLUSIONS: The associations
      identified within the research hierarchy suggest not only new avenues for
      etiologic research, but also priorities for research focus.

PMID- 9915606
TI  - Seven-year changes in physical fitness, physical activity, and lipid profile in
      the CARDIA study. Coronary Artery Risk Development in Young Adults.
AB  - PURPOSE: To relate seven year changes in physical fitness and physical activity
      in the young adult population to changes in the plasma lipid profile and to
      examine the influence of weight change on those relationships. METHODS: The
      participants in this observational study were the 1777 black and white men and
      women, ages 18-30 at entry into the Coronary Artery Risk Development in Young
      Adults (CARDIA) cohort, who completed a symptom-limited graded treadmill exercise
      test and had an overnight fasting blood draw at both the Baseline (1985-86) and
      Year 7 (1992-93) exams. CARDIA, a longitudinal study of the relationships of
      lifestyle and physiological variables to the development of coronary heart
      disease risk factors, consists of population-based cohorts in Birmingham,
      Alabama, Minneapolis, Minnesota and Chicago, Illinois and a cohort recruited from
      the membership of a large, pre-paid health care plan, broadly representative of
      the population, in Oakland, California. RESULTS: All race/gender groups
      experienced mean decreases in physical fitness and self-reported physical
      activity and increases in weight. Decreased fitness was associated with decreased
      high density lipoprotein-cholesterol (HDL-C), and conversely, increased fitness
      was associated with increased HDL-C. The correlation coefficients of change in
      fitness with change in HDL-C ranged from 0.17 in white men and black women to
      0.24 in white women (P < 0.001 for all race/gender groups). Change in fitness was
      minimally correlated with change in low density lipoprotein-cholesterol (LDL-C)
      in all groups (r ranged from -0.09 in black women to -0.20 in white women),
      triglycerides (TG) in men and white women (r ranged from -0.10 to -0.15), and
      total cholesterol (TC) in white men and women (r = -0.11 and -0.15,
      respectively). The magnitude of these correlations was further reduced with
      adjustment for weight change. Correlations between change in activity and change
      in lipid and lipoprotein values were generally weak or nonexistent, except for
      the suggestion of a small, direct relationship with change in HDL-C in black and
      white women (r = 0.14 and r = 0.11, respectively). All of the weight change
      adjusted correlations were essentially unaffected by further adjustment for
      baseline fitness or activity and other covariates. CONCLUSIONS: Decreased fitness
      during young adulthood is associated with unfavorable changes in lipid profile,
      explained mostly by increased weight. Lack of association between change in
      activity and change in lipid profile observed in this study may be due, in part,
      to imprecision of activity measurement.

PMID- 9915607
TI  - Positive association between resting pulse and cancer incidence in current and
      former smokers.
AB  - PURPOSE: To evaluate the association between resting pulse and cancer incidence
      in older persons. METHODS: A cohort of 2819 persons, aged 65 to 102 years at
      baseline, was followed for the development of cancer from 1982 through 1993 by
      linkage to a statewide cancer registry; 494 incident cases were identified.
      Resting radial pulse (beats per minute) was measured during an in-person
      interview at baseline, and sex-specific quintile cutpoints were used in the
      analysis. RESULTS: After adjustment for age, body mass, smoking, and physical
      activity, there was a positive association between pulse and cancer incidence in
      men: compared to men with a pulse of < 63, men with a pulse of 63-68 (relative
      risk (RR); 95% confidence interval (CI): RR = 1.68; CI = 1.06-2.66), 69-74 (RR =
      1.54; CI = 0.95-2.49), 75-82 (RR = 1.62; CI = 1.03-2.55), and > 82 (RR = 1.63; CI
      = 1.03-2.65) were at elevated risk for any cancer. This association remained
      unchanged after further adjustment for cardiovascular comorbidity, diabetes,
      alcohol use, high level of depressive symptoms, and low self-perceived health
      status. Exclusion of cases diagnosed in the first two years of follow-up did not
      alter the association. There was no overall association between pulse and cancer
      incidence in women. Analyses stratified by smoking status showed that the pulse
      and cancer association was strongest in ever smokers for both men and women. In
      subsite analysis for men, pulse was mainly associated with smoking-related tumors
      as a group and colorectal and prostate cancer. CONCLUSIONS: These data suggest
      that resting pulse is associated with cancer incidence, mainly among ever
      smokers.

PMID- 9915609
TI  - Who participates in population based studies of visual impairment? The Salisbury
      Eye Evaluation project experience.
AB  - PURPOSE: To describe characteristics of respondents and nonrespondents to a home
      questionnaire and comprehensive clinical examination in a population of elderly
      Americans. METHODS: The SEE project is a population-based study of age-related
      eye diseases, visual impairment, and functional status of individuals aged 65 to
      84. Potential participants were identified using the Health Care Financing
      Administration Medicare data base for Salisbury, MD: After sending out an
      introductory letter, a trained interviewer visited potential participants in
      their homes, obtained their consent to participate, administered a short
      screening interview that included questions about their general health and
      vision, and administered an extensive questionnaire on their diet, medical
      history, and difficulty performing activities related to vision. The interviewer
      then scheduled an appointment for the participants to visit a central site for an
      exam. Potential participants could fall into one of two refusal groups; refusal
      to take part in the study before the home questionnaire or prior to the clinic
      visit. RESULTS: The overall response rate for the clinic visit was 65%. Compared
      to individuals with complete exams, the two groups of refusals were older, less
      likely to have any college education, more likely to report poor health status,
      and more likely to need help with Independent Activities of Daily Living
      (IADL's). Participants with complete home questionnaires that failed to come to
      the clinic were more likely to have Mini-Mental scores below 25. There were not
      significant differences by race, gender, or self reported vision status among the
      three groups. CONCLUSIONS: Population-based studies requiring an in-clinic
      examination may selectively under-sample those with health and mental
      difficulties. These differential responses may introduce bias in the study
      results and need to be addressed when assessing the burden, type and severity of
      disease in the community. However, self-report of visual status was similar among
      refusals and participants in this study on vision.

PMID- 9915608
TI  - Depressive symptoms and mortality in older Mexican Americans.
AB  - PURPOSE: We examined the prevalence of comorbid depressive symptomatology and
      leading chronic medical conditions, and their influence on death rates in older
      Mexican Americans. METHODS: Data from the Hispanic Established Population for the
      Epidemiologic Study of the Elderly (EPESE) were used. Differences in death rates
      across sociodemographics, self-ratings of health, and health conditions were
      examined with analysis of variance statistics. Logistic regression models were
      used to examine main effects and interaction effects of each medical condition
      separately and in conjunction with depressive symptomatology. RESULTS: Bivariate
      analyses indicated that death rates were substantially higher when a high level
      of depressive symptoms was comorbid with diabetes (OR = 3.84, 95% CI = 2.55
      5.78), cardiovascular disease (OR = 4.04, 95% CI = 2.36-6.91), hypertension (OR =
      2.27, 95% CI = 1.57-3.27), stroke (OR = 3.00, 95% CI = 1.44-6.15), and cancer (OR
      = 4.46, 95% CI = 2.48-8.01). Multivariate analyses indicated a synergistic effect
      for comorbid diabetes and depressive symptoms such that the odds of having died
      among diabetics with high levels of depressive symptoms (OR = 4.03, 95% CI = 2.67
      6.11) were three times that of diabetics without high levels of depressive
      symptoms (OR = 1.36, 95% CI = 0.89-2.06). CONCLUSIONS: High levels of depressive
      symptoms concomitant with major chronic medical conditions elevate the risk for
      death among older Mexican Americans. Given the fact that depression is often
      unrecognized and undertreated in the elderly, awareness of the potential for loss
      of life as well as the potential for treatment may help to improve this situation
      not only for older Mexican Americans, but for older adults in general.

PMID- 9915610
TI  - Cancer occurrence in the elderly: agreement between three major data sources.
AB  - PURPOSE: To explore agreement on cancer occurrence and site among Medicare Part
      A, Massachusetts Cancer Registry, and death certificates. METHODS: We linked
      these data sources with the cohort of the population-based East Boston Senior
      Health Project, a component of the National Institute on Aging's Established
      Populations for Epidemiologic Studies of the Elderly. The cohort consists of 905
      subjects dying between January 1986 and December 1990. RESULTS: We detected the
      following agreements on cancer occurrence: hospitalization data and death
      certificates (kappa = 0.70), hospitalization and cancer registry data (kappa =
      0.59), and cancer registry and death certificate data (kappa = 0.50). Measures of
      agreement changed little when the analyses were stratified by age, sex, calendar
      year and place of death, autopsy performance, cigarette smoking or alcohol
      consumption. Site-specific agreements were higher for colorectal and respiratory
      tract cancer compared to breast and prostate across all three comparisons.
      CONCLUSIONS: The results should assist epidemiologists to better understand the
      strengths and limitations of these data sources.

PMID- 9915611
TI  - IRB review: necessary, nice or needless?

PMID- 9915612
TI  - Cancer among farmers: a meta-analysis.

PMID- 9915613
TI  - The path analysis approach for the multivariate analysis of infant mortality
      data.

PMID- 9915614
TI  - Hormonal effects on the brain.
AB  - Changes in seizure frequency over the course of the menstrual cycle (i.e.,
      catamenial epilepsy) have long been documented. Ovarian steroid hormones have a
      number of important short- and long-term effects on the brain that may contribute
      to this phenomenon. In particular, estrogen induces structural and functional
      changes in hippocampal neurons which may contribute significantly to increasing
      seizure susceptibility. This article reviews the mechanisms of action of steroid
      hormones on the basis of findings in animal models, with particular emphasis on
      the effects of estrogen on the hippocampus.

PMID- 9915615
TI  - Hormonal effects on epilepsy in women.
AB  - Some female gonadal and adrenal steroid hormones and their related pituitary
      peptides have neuroactive effects that can influence seizures. These effects may
      play a significant role in the pathophysiology of epilepsy, the pattern of
      seizure occurrence, therapeutic interventions using naturally occurring hormones,
      and the development of hormone-based neuroactive synthetic analogues with potent
      antiepileptic properties.

PMID- 9915616
TI  - Obstetric and gynecologic care of women with epilepsy.
AB  - Optimal gynecologic and obstetric care for women with epilepsy requires a
      multidisciplinary approach throughout the various life stages. Epilepsy has
      important effects on puberty, contraceptive efficacy, pregnancy and fetal
      development, and menopause. This article discusses these effects and makes
      recommendations for gynecologic and obstetric care of patients with epilepsy,
      with particular focus on pregnancy. Despite very real risks to both the
      developing fetus and the mother, the majority of women with epilepsy--with
      appropriate pregnancy planning and management--have good pregnancy outcomes.

PMID- 9915617
TI  - Neurologic care of pregnant women with epilepsy.
AB  - Epilepsy is a common neurologic condition in women of reproductive age. Although
      their risks are greater than those for women in the general population, the
      majority of women with epilepsy have a good pregnancy outcome. An understanding
      of the risks and appropriate management of both the pregnancy and epilepsy in
      these patients is essential for their physicians. Health-care providers should
      discuss contraception and reproductive issues with all of their female patients
      with epilepsy as they enter reproductive age. Optimal care requires prepregnancy
      counseling, including information about contraception, dietary folate
      supplementation, and the risks related to pregnancy. Although antiepileptic drugs
      (AEDs) have been implicated as the major cause of teratogenesis in infants born
      to mothers with epilepsy, uncontrolled epilepsy is also associated with maternal
      and fetal risk. Therefore, optimal seizure control during pregnancy remains an
      important goal for women with epilepsy. Women with epilepsy should be counseled
      about breast-feeding their infants and supported in their decision. The
      recommendations in this article reflect those of a Practice Parameter developed
      by the American Academy of Neurology Quality Standards Subcommittee.

PMID- 9915618
TI  - Effects of epilepsy on women's reproductive health.
AB  - Reproductive dysfunctions are common and wide-ranging in women with epilepsy.
      Menstrual cycle disruption, anovulatory cycles, disturbances in hypothalamic
      and/or pituitary hormones, and disturbances in gonadal steroids are more common
      among women with epilepsy. Sexual dysfunction can present as either disorders of
      desire or physiologic arousal, but the most common dysfunction appears to be an
      inadequate initial physiologic arousal response. Reproductive dysfunctions may be
      due to psychologic, pharmacologic, or physiologic factors. Physicians should
      routinely question all women with epilepsy regarding their reproductive and
      sexual health. A full history, a complete physical, and laboratory evaluations
      with endocrinologic work-up should be performed in any woman who reports a
      reproductive dysfunction. Treatment and/or referral to a gynecologist or
      endocrinologist should be initiated as appropriate.

PMID- 9915619
TI  - Counseling women with epilepsy.
AB  - All persons with epilepsy have a right to timely, accurate, culturally sensitive
      information that will help them manage their seizures and their lives
      successfully. The goals of counseling are to provide guidance for women with
      epilepsy in making informed choices, to promote self-management practices that
      will decrease health risks, and to provide comprehensive answers about relevant
      issues. Four broad areas that should be covered in counseling women with epilepsy
      include access to care, unique health needs of women with epilepsy, personal care
      and safety, and social and community relationships. These are described here in
      more detail.

PMID- 9915620
TI  - Autonomic brainstem projections to the pancreas: a retrograde transneuronal viral
      tracing study in the rat.
AB  - The present study describes brainstem nuclei that participate in the autonomic
      innervation of the pancreas, using a retrograde viral transneuronal tracing
      technique. It aimed at identifying the neuronal architecture of the
      parasympathetic, gustatory-induced insulin release by the endocrine pancreas
      (preabsorptive insulin response, PIR). Autonomic pathways organized for reflex
      adjustments of the end organ, as it happens in the PIR, involve relatively simple
      circuits. This implies a short brainstem circuit from the rostral gustatory
      nucleus of the solitary tract to the dorsal motor nucleus of the vagus. The
      present findings confirm projections to the pancreas, originating from
      preganglionic neurons in the dorsal motor nucleus of the vagus. Transneuronal
      labeling was detected in the medial, and to a lesser extent in the lateral
      nucleus of the solitary tract mainly at caudal and intermediate levels.
      Furthermore, infected neurons were seen in the brainstem in the dorsal and
      ventral part of the medullary reticular formation, in the area postrema and in
      the raphe nuclei. Sparse labeling was found in the gustatory zone of the nucleus
      tractus solitarius. These results indicate that a direct connection between the
      rostral nucleus tractus solitarius and the medial dorsal motor nucleus of the
      vagus is very unlikely, so that one or more intermediate stations may be
      involved. Candidates to complete this pathway are the intermediate or caudal
      nucleus tractus solitarius, the medullary reticular formation or the parabrachial
      nucleus.

PMID- 9915621
TI  - The changes in the nervous structures under the chemical sympathectomy with
      guanethidine.
AB  - The process of sympathectomy of white rats was achieved by injecting guanethidine
      intraperitoneally every day for 5.5 weeks at doses of 75 mg/kg of animal's
      weight. This process of sympathectomy was checked according to ganglion
      cervicothoracicum neurocytes state. The material was taken on days 1, 14, 30, 90
      and 180 after cessation of guanethidine injections. It was ascertained that full
      sympathectomy under prolonged injections of high doses of guanethidine is reached
      at 5-6 months after the cessation of the injections, though pronounced total
      degeneration of gnl. stellatum neurocytes is marked on the 14th-30th days after
      cessation of the guanethidine injections. The following gradient of damaging
      influence of guanethidine was revealed: sympathetic gnl. cervicothoracicum
      neurocytes gnl. nodosum afferent neurocytes-neuromuscular synapsis skeletal
      muscle.

PMID- 9915623
TI  - Distribution of myenteric NO neurons along the guinea-pig esophagus.
AB  - Intrinsic nitrergic (NO) neurons of the guinea-pig esophagus were histologically
      studied to elucidate the physiological significance of the myenteric plexus
      located in the esophageal striated muscle and smooth muscle of the lower
      esophageal sphincter. Double staining for PGP 9.5 immunohistochemistry and NADPH
      diaphorase histochemistry, which depicts whole neuronal elements and nitrergic NO
      neurons, respectively, revealed that the plexus had different network patterns
      along the entire course of the esophagus, and that NADPH-diaphorase positive
      neurons made up on average 69% of the total number of myenteric neurons. Motor
      endplates of the esophageal striated muscles that were stained by
      acetylcholinesterase histochemistry, were often observed in association with
      NADPH-diaphorase positive varicose fibers that were traced to the myenteric
      ganglia, though their direct continuity with the neuronal cell bodies could not
      be ascertained. We conclude that the myenteric NADPH-diaphorase positive neurons
      in the guinea-pig esophagus contribute to the innervation of the striated muscles
      as well as the smooth muscles of the lower esophageal sphincter.

PMID- 9915622
TI  - Activation of beta3-adrenoceptors by exogenous dopamine to lower glucose uptake
      into rat adipocytes.
AB  - The effect of dopamine hydrochloride on beta3-adrenoceptors was studied in
      isolated adipocytes of Wistar rats using uptake of [14C]-deoxy-D-glucose (2-DG)
      as the indicator. Dopamine induced a concentration-dependent decrease of 2-DG
      uptake into adipocytes in a manner which was not modified by haloperidol at
      concentrations sufficient to block dopaminergic receptors. Failure of blockade
      was also observed in samples receiving the pretreatment with a mixture of
      SCH23390 and domperidone, the dopaminergic antagonists. Absence of dopaminergic
      receptors in rat white adipocytes was further supported by the findings that
      dopaminergic agonists did not modify the glucose uptake and the negative response
      to receptor antibodies in immunoblotting analysis. Pindolol and propranolol
      reversed this inhibition of dopamine in a concentration-dependent manner.
      However, this action of dopamine was not affected by prazosin at concentrations
      sufficient to block alpha-adrenoceptors. Effect of dopamine was reduced in the
      presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of
      cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. Direct
      effect of exogenous dopamine on beta3-adrenoceptors was identified using the
      antibody for beta3-adrenoceptors that reversed the inhibition of dopamine. These
      results suggest that dopamine can activate beta3-adrenoceptors to lower glucose
      uptake into rat white adipocytes which lack dopaminergic receptors.

PMID- 9915624
TI  - Lack of induction of substance P gene expression by hypoxia and absence of
      neurokinin 1-receptor mRNAs in the rat carotid body.
AB  - Peripheral chemoreceptors are commonly thought to respond to hypoxia by releasing
      neurotransmitters from the type 1 cells of the carotid body; these molecules then
      bind to post-synaptic receptors on the carotid sinus nerve. The tachykinin
      substance P (SP) may act as an important neurotransmitter/neuromodulator in
      hypoxic chemotransmission in peripheral arterial chemoreceptors. In order to
      elucidate the role of SP in modulating hypoxic chemotransmission, we have used
      quantitative in situ hybridization histochemistry, to determine the effect of
      hypoxia on SP gene induction, and the localization of neurokinin 1 (NK-1)
      receptor mRNA in the carotid body and petrosal ganglia complex in rats at 21 days
      post-natal age. For comparison, we also determined: (1) the effect of hypoxia on
      tyrosine hydroxylase (TH) gene induction and (2) the localization of the mRNA
      encoding the D2-dopamine receptor. SP mRNA was not detected in the rat carotid
      body during normoxia and its expression was not induced after a 1 h of exposure
      to hypoxia (10% O2/90% N2), a stimulus that was sufficient to cause a significant
      increase (P < 0.01) in TH mRNA levels in the carotid body. Both SP and TH mRNAs
      were abundantly expressed in multiple cells in the petrosal and the jugular
      ganglia. However, these mRNAs were not co-localized and SP and TH mRNA levels
      were not affected by hypoxia in these ganglia. Although D2-dopamine receptor mRNA
      was abundantly expressed in the rat carotid body, we found no evidence of NK-1
      receptor mRNA in the carotid body. In contrast, both NK-1 receptor mRNA and D2
      dopamine receptor mRNA were present in petrosal ganglion cells. In the rat, SP
      does not appear to modulate hypoxic chemotransmission by being made in and
      released from type 1 cells in the carotid body, and neither does SP modulate the
      activity of type 1 cells by binding to NK-1 receptors on these cells.

PMID- 9915625
TI  - Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1
      receptors in the nucleus tractus solitarius.
AB  - An antisense oligodeoxynucleotide which specifically blocked the production of
      the glutamate receptor subtype NMDAR1 was administered to the nucleus tractus
      solitarius (NTS) in order to examine the role of this receptor in baroreflex
      control of heart rate. Baseline blood pressure and heart rate were unchanged by
      NTS treatment with the antisense oligodeoxynucleotide to the NMDAR1 receptor
      subunit. However, the reflex bradycardia evoked in response to the hypertension
      induced by bolus administration of phenylephrine was significantly attenuated
      following bilateral NTS antisense oligodeoxynucleotide treatment. Administration
      of the corresponding mismatched antisense oligodeoxynucleotide did not
      significantly alter the reflex bradycardia. These data indicate that NMDAR1
      receptors are involved in neurotransmission in the baroreflex arc at the level of
      the NTS. The specificity of antisense oligodeoxynucleotides may prove to be a
      useful technique to analyze the role of receptor subtypes mediating
      neurotransmission in central pathways.

PMID- 9915626
TI  - Sympathetic hyperactivity in Wistar rats with insulin-resistance.
AB  - In an attempt to know the effect of sustained hyperinsulinemia on sympathetic
      function, plasma norepinephrine (NE) and glucose levels were measured in Wistar
      rats with insulin resistance. Both the basal plasma glucose and the plasma NE
      levels in insulin-resistant rats were markedly higher than that obtained in
      normal or streptozotocin (STZ)-induced diabetic rats. Treatment with guanethidine
      and prazosin reversed these sympathetic hyperactive responses in insulin
      resistant rats. Moreover, increase of plasma insulin in rats receiving an
      intraperitoneal glucose challenge test confirmed the mediation of endogenous
      insulin in this sympathetic hyperactivity. These results suggest an increase of
      sympathetic activity in insulin-resistant state that may be related to the
      hypertension-prone associated with diabetes mellitus in clinics.

PMID- 9915627
TI  - Evaluation of pulmonary afferent fibers in the nucleus tractus solitarius: a
      horseradish peroxidase and c-fos like immunohistochemical study in the rat.
AB  - Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected
      into the rat lung parenchyma, just beneath the lateral surface of the left upper
      lobe, in order to demonstrate the pulmonary afferents. This injection resulted in
      heavy accumulation of labeled fibers in the medial nucleus tractus solitarius
      (NTS). The labeling in the medial NTS was divided into the ventral and dorsal
      parts at the level around the obex. Some labeling was found in the commissural
      and ventrolateral NTS. Further confirmation of the central distribution of these
      pulmonary afferent fibers was made by the expression of fos-like immunoreactivity
      (FOS-LI) induced by injection of formalin into the lung. It is concluded that
      afferents of lung parenchyma terminating predominantly in the medial NTS might
      come from alveoli and terminal bronchioles, because WGA-HRP and formalin injected
      into the lung are considered to be confined to the terminal areas of the
      respiratory tract.

PMID- 9915628
TI  - Attenuation of regional differentiation of sympathetic nerve activity during
      sleep in humans.
AB  - The purpose of the present study was to clarify how the regional differentiation
      of sympathetic nerve activity (SNA) is modified during natural sleep in humans.
      In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been
      reported to discharge independently according to a regional differentiation of
      SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been
      documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the
      present study, we measured MSNA and SSNA simultaneously using a double recording
      technique of microneurography in eight healthy volunteers during natural sleep,
      and analyzed how MSNA and SSNA can be synchronized. We found that the
      synchronicity of MSNA and SSNA was accelerated in correlation with the deepening
      of the non-rapid eye movement (nonREM) sleep stages. We also documented that the
      burst properties of MSNA different from those of SSNA in wakefulness become
      similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The
      synchronicity of MSNA and SSNA is presumably caused by a reduced effect of
      central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present
      findings suggest that the regional differentiation of sympathetic nerve activity
      is attenuated with the deepening of nonREM sleep stages.

PMID- 9915629
TI  - Changes in cholinergic responses of sweat glands during denervation and
      reinnervation.
AB  - Functional sudomotor responses have been studied in sweat glands reinnervated
      after sciatic nerve crush and partially denervated by cisplatin intoxication in
      the mouse. The sudomotor function mediated by the sciatic nerve was evaluated by
      silicone imprints on the plantar surface of the hindpaws. Five days after nerve
      crush, completely denervated sweat glands became unresponsive to cholinergic
      stimulation with pilocarpine. During the following weeks, the number of
      reinnervated, reactive sweat glands increased progressively to reach a maximum of
      89% of preoperative control counts by 40 days after nerve crush. At this time,
      the mean volume of sweat secreted per gland was normal, but reinnervated glands
      showed a secretory activity abnormally sustained over time after pilocarpine
      stimulation and, on the other hand, had an increased resistance to the inhibition
      of secretion induced by atropine. The effects of cisplatin administration on
      sudomotor function were investigated in two groups of mice, one treated with high
      doses of cisplatin (10 mg/kg/week for 4 weeks) and another treated with low doses
      of cisplatin (5 mg/kg/week for 8 weeks). Cisplatin intoxication produced abnormal
      sudomotor responses indicative of denervation from cumulative doses of 10 mg/kg.
      The first abnormality found was a partial resistance of sweat glands to atropine,
      followed by a decrease in the sweat output per gland and finally a decline in the
      number of sweat glands activated by pilocarpine. These abnormalities in the
      sudomotor responses were more pronounced in mice treated with a high dose than in
      those with a lower dose regime.

PMID- 9915630
TI  - Stellate neurones innervating the rat heart express N, L and P/Q calcium
      channels.
AB  - The aim of the study was to investigate the kinetic properties and identify the
      subtypes of Ca2+ currents in the cardiac postganglionic sympathetic neurones of
      rats. Neurones were labelled with a fluorescent tracer--Fast-Blue, injected into
      the pericardial cavity. Voltage-dependent Ca2+ currents were recorded from
      dispersed stellate ganglion cells that showed Fast Blue labelling. Only high
      threshold voltage-dependent Ca2+ currents were found in the somata of cardiac
      sympathetic neurones. Their maximum amplitude, mean cell capacitance and current
      density were respectively: 0.67 nA, 19.3 pF and 36.4 pA/pF (n = 21). The maximum
      Ca2+ conductance was 51.3 nS (n = 14). Half activation voltage equalled +11.0 mV
      and the slope factor for conductance 11.1 (n = 14). As tested with a 10 s pre
      pulse, the Ca2+ current began to inactivate at -80 mV. Half inactivation voltage
      and slope factor for steady-state inactivation were -36.6 mV and 14.1 (n = 9),
      respectively. Saturating concentration of L channel blocker (nifedipine), N
      channel blocker (omega-conotoxin-GVIA), P/Q channel blocker (omega-Agatoxin-IVA)
      and N/P/Q channel blocker (omega-conotoxin-MVIIC) reduced the total Ca2+ current
      by 26.8% (n = 7), 57.1% (n = 12), 25.9% (n = 6) and 69.4% (n = 6), respectively.
      These results show that the somata of cardiac postganglionic cardiac sympathetic
      neurones contain significant populations of N, L and P/Q high threshold Ca2+
      channels.

PMID- 9915631
TI  - Effects of clonidine on power spectral analysis of heart rate variability in mild
      essential hypertension.
AB  - Patients with essential hypertension often show alterations of the autonomic
      nervous system. We evaluated the sympathetic and parasympathetic drive to the
      heart in 12 mildly hypertensive patients and 9 healthy subjects by power spectral
      analysis of heart rate variability. All subjects underwent measurements of RR
      interval, low (LF) and high frequency (HF) components of heart rate variability,
      LF/HF ratio and blood pressure in the resting and sitting positions, both before
      and after oral clonidine (300 microg), a central sympatholytic agent. In the
      supine position before clonidine, hypertensive patients had higher blood pressure
      and lower HF values than healthy subjects. Clonidine induced increases in RR
      interval and HF in both groups, while LF and LF/HF ratio decreased in healthy
      subjects, but not in hypertensive patients. On assuming the sitting position,
      both groups showed reductions in RR and HF and increments in LF and LF/HF. In
      healthy subjects, the response to the postural challenge was unaffected by
      clonidine. In contrast, hypertensive patients showed no changes in LF and LF/HF
      ratio, and a significantly lower decrease in HF. These differences were probably
      due to the existence of two subsets of patients, one exhibiting similar responses
      to clonidine as healthy subjects, and the other showing no appreciable response
      to the drug. These results suggest that hypertensive patients have an altered
      sympatho-vagal balance to the heart, which can be unmasked by clonidine. This
      phenomenon should be taken into account to achieve a better control of the
      overall cardiovascular risk of hypertensive patients.

PMID- 9915632
TI  - Angiotensin II receptors within the nucleus of the solitary tract mediate the
      developmental attenuation of the baroreceptor vagal reflex in pre-weaned rats.
AB  - This study tested the hypothesis that baroreceptor vagal reflex (BVR) attenuation
      in developing rats, which occurs between postnatal ages (P) of 10 to 20 days old,
      is due to a central action of angiotensin II (Ang II). In urethane or halothane
      anaesthetised mature (P > 45) or pre-weaned rats (P14-18), BVR sensitivity was
      estimated as the ratio between the fall in heart rate and the increase in
      arterial pressure induced by i.v. phenylephrine. An Ang II AT1 receptor
      antagonist, losartan, was administered intra-venously (i.v.) or microinjected
      into brainstem structures. In pre-weaned rats BVR sensitivity was increased
      significantly by losartan (5 mg/kg; urethane anaesthesia: p < 0.01; halothane
      anaesthesia: p < 0.05) while a larger dose (10 mg/kg) was ineffective in mature
      animals. In pre-weaned rats, microinjection of losartan (500 pmol) into the
      nucleus tractus solitarii (NTS) but neither area postrema nor subjacent nuclei,
      reversibly increased the sensitivity of BVR (+89 +/- 19%; p < 0.01, n = 12).
      Microinjection of losartan (500 or 1500 pmol) into the NTS of mature rats did not
      change the BVR. An AT2-antagonist, PD123-319 did not restore the BVR sensitivity
      in pre-weaned rats. Thus, AT1 receptors located within the NTS play a pivotal
      role in the developmental attenuation of the BVR in pre-weaned rats.

PMID- 9915633
TI  - Activation of NMDA and non-NMDA receptors in the caudal ventrolateral medulla
      dilates the airways.
AB  - The caudal ventrolateral medulla (CVLM) participates in the central control of
      airway caliber. For example, both electrical and chemical stimulation of the CVLM
      decrease total lung resistance by withdrawing cholinergic input to airway smooth
      muscle. Although cell bodies in the CVLM have been shown to play an important
      role in mediating the central control of airway caliber, the pharmacological
      mechanism in this brainstem region responsible for causing this airway dilation
      is unknown. We, therefore, examined the role played by ionotropic excitatory
      amino acid receptors in the CVLM in the control of airway caliber in chloralose
      anesthetized dogs. We found that microinjection of 3.9 pmol of NMDA or AMPA or
      quisqualate into 12 sites in the CVLM decreased total lung resistance by 1.5 +/-
      0.2 cm H2O l(-1) s(-1) (p < 0.05), and that microinjection of 3.9 pmol of kainic
      acid into 9 in the CVLM decreased total lung resistance by 0.5 +/- 0.1 cm H2O l(
      1) s(-1) (p < 0.05). The decrease in total lung resistance evoked by either NMDA
      or AMPA or quisqualate was not different (p > 0.05) while that evoked by kainic
      acid was significantly smaller. Additionally, microinjection of NMDA or AMPA or
      quisqualate caused a small but significant decrease in mean arterial pressure and
      heart rate (p < 0.05). These experiments demonstrate that the airway dilation
      evoked by stimulation of excitatory amino acid receptors in the CVLM is mediated
      by both NMDA and non-NMDA receptors.

PMID- 9915634
TI  - Influence of the cold pressor test on the middle cerebral artery circulation.
AB  - Cold pressor test (CPT) evokes generalized activation of the sympathetic nervous
      system (SNS). The activity of SNS may be estimated by monitoring the mean blood
      velocity (v(m)) in the middle cerebral artery (MCA) by using a transcranial
      Doppler monitoring system (TCD). To determine the response of SNS, we studied the
      v(m) during CPT. Thirty-four healthy volunteers, 13 female and 21 male (mean age
      34 +/- 9.5 years, range 18 to 55 years) participated in our study. The experiment
      consisted of a 5-min baseline period followed by a 3-min immersion of the right
      hand in ice water. Blood velocity in both MCA's was monitored by bitemporal 2 MHz
      probes by using a Multi-Dop X4. MAP and heart rate (HR) were measured
      simultaneously by a Finapres non-invasive blood pressure monitor and a
      computerized ECG system. End-tidal CO2 (Et-CO2) was measured with an infrared
      capnograph. To determine v(m) over a chosen time interval the TCD-8 software was
      utilized. The results showed that during CPT v(m), MAP, and HR increased
      significantly (P < 0.01) for 9.8%, 18.5%, and 3.6%, respectively. Et-CO2 did not
      change significantly (P > 0.05). The increase of v(m) was also significantly
      higher in the stimulated hemispheres (P = 0.005) regarding to unstimulated ones.
      The increase of v(m) during CPT was not gender dependent. To establish the
      association between variables the models of multivariate regression were used.
      Multiple regression CPT model was significant (P < 0.01) and fitted data
      moderately well (R2 = 0.28). MAP and Et-CO2 were significant in the model (P <
      0.01). It seems that the reactivity of the SNS can be estimated by measuring v(m)
      with TCD during CPT.

PMID- 9915635
TI  - Right ventricular responses to vagus stimulation of fibers to discrete cardiac
      regions in dog hearts.
AB  - To investigate the role on the right ventricular function of the parasympathetic
      nerves in discrete cardiac regions, we studied the effects of stimulation of the
      intracardiac parasympathetic nerves to the atrioventricular (AV) nodal area
      (AVPS) or sinoatrial (SA) nodal area (SAPS), and stimulation of the cervical
      vagus nerves (CVS) on the right atrial and ventricular function in the
      autonomically decentralized heart of the anesthetized dog. AVPS prolonged AV
      conduction time (AVCT) and decreased the ventricular rate without changes in
      atrial rate, right atrial 'a' wave pressure (RAP), its first derivative (RAd
      P/dt), right ventricular pressure (RVP) and its first derivative (RVd P/dt) in
      the spontaneously beating heart. On the other hand, AVPS prolonged the AVCT in
      the atrium paced electrically and further decreased the ventricular rate with
      decreases in ventricular pressure responses but not atrial responses. SAPS
      decreased atrial and ventricular rates without AVCT changes and attenuated the
      right atrial and ventricular pressure responses. In the atrial paced heart, SAPS
      decreased the ventricular responses less than those responses in the
      spontaneously beating heart with similar decreases in the atrial pressure
      responses, but it changed neither the AVCT nor ventricular rate. On the other
      hand, CVS decreased the atrial and ventricular rate or pressure responses, and
      increased the AVCT. CVS in the paced heart also decreased the atrial and
      ventricular pressure responses with the prolongation of AVCT. The cardiac
      responses to parasympathetic stimulations were abolished by atropine. These
      results suggest that AVPS decreases ventricular rate without direct right
      ventricular pressure effects but the negative chronotropic effects of AVPS and
      SAPS decrease the ventricular pressure responses rate-dependently in the dog
      heart.

PMID- 9915637
TI  - Uncertainties in probabilistic nuclear accident consequence analysis.

PMID- 9915636
TI  - Consensus statement on the diagnosis of multiple system atrophy.
AB  - We report the results of a consensus conference on the diagnosis of multiple
      system atrophy (MSA). We describe the clinical features of the disease, which
      include four domains: autonomic failure/urinary dysfunction, parkinsonism and
      cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the
      relative importance of these features. The diagnosis of possible MSA requires one
      criterion plus two features from separate other domains. The diagnosis of
      probable MSA requires the criterion for autonomic failure/urinary dysfunction
      plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis
      of definite MSA requires pathological confirmation.

PMID- 9915638
TI  - The report of the French Academy of Science: 'Problems associated with the
      effects of low doses of ionising radiation'.
AB  - In 1995 the French Academy of Science published a report on 'Problems associated
      with low doses of ionising radiation'. This report aroused interest among French
      speaking scientists and a translation in English was published a year later. The
      report pointed out that an important issue in radioprotection was not whether to
      accept or reject the linear no-threshold model but rather to test its validity.
      The aim of this review is to analyse the report and its recommendations, and to
      briefly indicate the progress which has been made and the questions which remain
      open. Three areas of the report are covered in this review: DNA repair,
      carcinogenesis and epidemiological data.

PMID- 9915639
TI  - Joint EC/USNRC expert judgement driven radiological protection uncertainty
      analysis.
AB  - The development of two probabilistic accident consequence codes sponsored by the
      European Commission and the United States Nuclear Regulatory Commission, COSYMA
      and MACCS respectively, was completed in 1990. These codes estimate the risks and
      other endpoints associated with accidents from hypothesised nuclear
      installations. In 1991, both commissions sponsored a joint project for an
      uncertainty analysis of these two codes. The main objective of this joint project
      was to systematically derive credible and traceable probability distributions for
      the respective code input variables. These input distributions will subsequently
      be used in two uncertainty analyses for each code separately. A formal expert
      judgement elicitation and evaluation process was used as the best available
      technique to accomplish that objective. This paper describes the process and some
      of the findings of the eight expert judgement exercises performed under the joint
      study.

PMID- 9915640
TI  - The Joint Convention on the Safety of Spent Fuel Management and on the Safety of
      Radioactive Waste Management: development and technical content.
AB  - During the process of negotiation of the Convention on Nuclear Safety it was
      recognised that the safe management of radioactive waste was also a subject of
      great international concern. It was not possible to cover this subject
      comprehensively in a Convention focusing on the safety of civil nuclear power
      plants but the need for a further Convention was identified in the preamble to
      the Convention on Nuclear Safety. Accordingly the procedures were started that
      led to the setting-up of an open-ended Group of Experts to agree the text of a
      new Convention. This article describes from a scientific and technical viewpoint
      the deliberations of the Group of Experts, the compromises needed to cover in a
      single Convention the safety of both spent fuel management and radioactive waste
      management, the last minute expansion of the scope to admit reprocessing, the
      delicate negotiations on the inclusion of material from military programmes and
      the contentious question of the transboundary movement of spent fuel and
      radioactive waste. The article also summarises and provides some commentary on
      the final provisions of the Convention as adopted by a Diplomatic Conference in
      Vienna in September 1997 and now open for signature.

PMID- 9915642
TI  - An IPSM sponsored intercomparison of surface contamination monitoring test
      results.
AB  - An intercomparison using two popular survey meters was arranged to assess the
      ability of participants to test surface contamination monitors in compliance with
      the requirements of the Ionising Radiations Regulations 1985. The instruments
      were circulated and the data returned were compared with the NRPB values. The
      major inconsistencies were caused by differences in the interpretation of what
      constitutes 1 Bq of 90Sr+ 90Y and in the conversion of the emission rate from
      (129)I plaques into a value of equivalent (125)I activity.

PMID- 9915641
TI  - Stochastic dose/risk assessment uncertainty and the concept of potential
      exposures.
AB  - Assessments of future potential doses and risks (e.g. in connection with
      radioactive waste disposal) can be associated with substantial uncertainties.
      These uncertainties are often incorporated into assessments using stochastic
      models, and give rise to doses characterised in probabilistic terms. Questions
      about how doses should be related to risks arise even in the case of
      deterministic dose assessments. However, results of a probabilistic dose
      assessment may lead to additional issues when interpreting them or attempting to
      convert them to risk for regulatory purposes. Some problems are shown to
      originate from the difference between the meaning of a probabilistic dose value
      and the definition of potential exposure. Others relate to the appropriate choice
      of, or approach to compliance with, a regulatory limit. A possible method for
      setting limits on probabilistic (potential) doses or risks is proposed, based on
      an accepted technique for determining detection limits.

PMID- 9915643
TI  - National waste management infrastructure in Ghana.
AB  - Radioactive materials have been used in Ghana for more than four decades.
      Radioactive waste generated from their applications in various fields has been
      managed without adequate infrastructure and any legal framework to control and
      regulate them. The expanded use of nuclear facilities and radiation sources in
      Ghana with the concomitant exposure to human population necessitates effective
      infrastructure to deal with the increasing problems of waste. The Ghana Atomic
      Energy Act 204 (1963) and the Radiation Protection Instrument LI 1559 (1993) made
      inadequate provision for the management of waste. With the amendment of the
      Atomic Energy Act, PNDCL 308, a radioactive waste management centre has been
      established to take care of all waste in the country. To achieve the set
      objectives for an effective waste management regime, a waste management
      regulation has been drafted and relevant codes of practice are being developed to
      guide generators of waste, operators of waste management facilities and the
      regulatory authority.

PMID- 9915644
TI  - Transgenerational carcinogenesis in mice.

PMID- 9915645
TI  - Dangerous goods safety advisers.

PMID- 9915646
TI  - Radiation from bomb tests could cause thyroid cancer, but screening program not
      advisable. US National Academy Press.

PMID- 9915647
TI  - The OSPAR Commission and Ministerial Meeting, 20-24 July 1998, Sintra Lisbon.

PMID- 9915648
TI  - The influence of distress on mothers' and fathers' reports of childhood emotional
      and behavioral problems.
AB  - This study examined the effect of parental distress on mothers' and fathers'
      reports of children's emotional and behavioral problems. The subjects were the
      parents of 696 children aged 10 to 11 or 14 to 15 years living in two-parent
      families in the community. The study utilized an extended version of the model
      previously employed by Fergusson, Lynskey, and Horwood (1993) to examine the
      impact of maternal depression on mothers' reports of children's behavior. In the
      present study, the extended model was used to assess the impact of distress on
      reports of childhood externalizing and internalizing problems obtained from both
      mothers and fathers. The results suggested that distress had little influence on
      mothers' or fathers' reports of childhood behavior problems. It is concluded that
      in community studies the size of any bias in mothers' and fathers' reports of
      childhood behavior problems due to parental distress is likely to be very small
      and of little clinical significance.

PMID- 9915649
TI  - Is a mild deficit in executive functions in boys related to childhood ADHD or to
      parental multigenerational alcoholism?
AB  - A mild deficit in executive functions has been hypothesized to be associated with
      attention deficit hyperactivity disorder (ADHD), with externalizing problem
      behaviors such as conduct disorder (CD) and with the vulnerability to alcoholism
      in sons of multi-generational alcoholics (SOMGAs). These three categories
      overlap, which raises concerns about the specificity of the hypothesized
      associations. In the present study, measures of executive functions (EFs) were
      tested in seventy-six 7- to 11-year-old boys: boys with ADHD but without a family
      history of addiction, SOMGAs, and controls. Specific deficits in EFs were found
      for boys with ADHD but not for SOMGAs. The association between a deficit in EFs
      and attention problems remained after controlling for externalizing problem
      behaviors, but not for the reverse. These results suggest that a mild deficit in
      EFs is specifically related to ADHD and that the deficits reported in boys with
      CD and in SOMGAs are due to relatively high attentional problems in these groups
      or due to other factors such as motivation.

PMID- 9915650
TI  - Social-cognitive and behavioral correlates of aggression and victimization in
      boys' play groups.
AB  - A contrived play group procedure was utilized to examine the behavioral and
      social-cognitive correlates of reactive aggression, proactive aggression, and
      victimization via peers. Eleven play groups, each of which consisted of six
      familiar African-American 8-year-old boys, met for 45-min sessions on five
      consecutive days. Social-cognitive interviews were conducted following the second
      and fourth sessions. Play group interactions were videotaped and examined by
      trained observers. High rates of proactive aggression were associated with
      positive outcome expectancies for aggression/assertion, frequent displays of
      assertive social behavior, and low rates of submissive behavior. Reactive
      aggression was associated with hostile attributional tendencies and frequent
      victimization by peers. Victimization was associated with submissive behavior,
      hostile attributional bias, reactive aggression, and negative outcome
      expectations for aggression/assertion. These results demonstrate that there is a
      theoretically coherent and empirically distinct set of correlates associated with
      each of the examined aggression subtypes, and with victimization by peers.

PMID- 9915651
TI  - Evidence for the continuity of early problem behaviors: application of a
      developmental model.
AB  - Evidence of the continuity of early problem behaviors in young girls and boys was
      examined developmentally. Data were gathered on 104 mother-child dyads from low
      income families when children were between 1 and 5 years of age. Difficult
      temperament, aggression, and noncompliance from 12 to 24 months, and
      externalizing and internalizing problems at 36 and 60 months, were assessed. The
      results provide evidence for the continuity of early behavioral and emotional
      problems and support for the early differentiation between internalizing and
      externalizing problems. Implications of the current findings for prevention
      efforts are presented.

PMID- 9915652
TI  - Pathways of risk for accelerated heavy alcohol use among adolescent children of
      alcoholic parents.
AB  - The current study examined two questions. First, do internalizing symptoms and
      externalizing behavior each mediate the relations between parent psychopathology
      (alcoholism, antisocial personality disorder, and affective disorder) and growth
      in adolescent heavy alcohol use? Second, are there gender differences in these
      mediated pathways? Using latent curve analyses, we examined these questions in a
      high-risk sample of 439 families (53% children of alcoholic parents; 47% female).
      Collapsing across gender, adolescent-reported externalizing behavior mediated
      both the relation between parent alcoholism and growth in heavy alcohol use and
      the relation between parent antisociality and growth in heavy alcohol use. Parent
      reported externalizing behavior only mediated the relation between parent
      antisociality and growth in heavy alcohol use in males. No support was found for
      internalizing symptoms as a mediator of these relations. Avenues are suggested
      for further exploring and integrating information about different mediating
      processes accounting for children of alcoholics' risk for heavy alcohol use.

PMID- 9915653
TI  - Specificity of dating aggression and its justification among high-risk
      adolescents.
AB  - Ninety-five high-risk adolescents were studied to determine whether their dating
      aggression and its justification as a response to interpersonal problems were
      specific to the current partner, general to dating relationships, or part of a
      global age-mate (same-sex peers and opposite-sex dating partners) aggression
      problem. Approximately one-third of males and two-thirds of females reported
      physical aggression against their current dating partner. Males' aggression (and
      its justification) toward their current dating partner was part of a generalized
      pattern of dating aggression, whereas for females, physical aggression against a
      current dating partner (and its justification) was partner-specific and unrelated
      to aggression in other relationships. Findings are discussed with regard to
      intervention and future research on adolescent dating aggression.

PMID- 9915655
TI  - Genetic and environmental influences on subtypes of conduct disorder behavior in
      boys.
AB  - Oppositional and conduct disorders are a heterogeneous collection of disruptive
      behaviors associated with diverse risk factors and varying outcomes. Data from
      males in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD)
      are used to explore the relative importance of genetic and environmental
      influences on four previously described disruptive subtypes: property violations,
      status violations, oppositional behavior, and aggression. Striking differences
      between results according to mother and child ratings are found, indicating the
      need to consider carefully the origin of rater differences. Child ratings
      indicate support for a general genetic liability, with greatest influence on
      property violations, oppositional behavior and aggression. Maternal ratings
      suggest that the genetic factors influencing conduct disorder behavior are more
      specific to the behavioral area, with the stronger genetic influence on property
      violations and aggression.

PMID- 9915656
TI  - Cognitive impairment and its relationship to psychopathic tendencies in children
      with emotional and behavioral difficulties.
AB  - This study investigated whether performance on the card playing task (Newman,
      Patterson, & Kosson, 1987) and the moral/conventional distinction measure predict
      level of childhood conduct problems as indexed by the Psychopathy Screening
      Device (Frick & Hare, in press). The card-playing task indexes the child's
      sensitivity to changes in reinforcement rate. The moral/conventional distinction
      measure indexes the child's sensitivity to the difference between moral
      transgressions which result in harm to another from conventional transgressions
      which more usually result in social disorder. The Psychopathy Screening Device
      indexes a behavioral syndrome that consists of two dimensions: affective
      disturbance and impulsive and conduct problems. Thirty-nine children with
      emotional and behavioral difficulties were presented with both measures.
      Performance on both measures did predict extent of behavioral disturbance.
      Moreover, there was a significant association between performance on the card
      playing tasks and the moral/conventional distinction. The results are interpreted
      within the response set modulation and violence inhibition mechanism models and
      by reference to recent work at the anatomical level.

PMID- 9915654
TI  - Psychiatric and psychological morbidity as a function of adaptive disability in
      preschool children with aggressive and hyperactive-impulsive-inattentive
      behavior.
AB  - Children with high levels of aggressive-hyperactive-impulsive-inattentive
      behavior (AHII; n = 154) were subdivided into those with (n = 38) and without (n
      = 116) adaptive disability (+AD/-AD) defined as a discrepancy between expected
      versus actual adaptive functioning. They were compared to each other and a
      control group of 47 normal children. Both AHII groups were more likely to have
      attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder,
      and conduct disorder than control children; more symptoms of general
      psychopathology; greater social skills deficits; more parental problems; and
      lower levels of academic achievement skills. Compared to AHII - AD children, AHII
      + AD children had (1) more conduct disorder; (2) greater inattention and
      aggression symptoms; (3) more social problems, less academic competence, and
      poorer self-control at school; (4) more severe and pervasive behavior problems
      across multiple home and school settings; and (5) parents with poorer child
      management practices. Thus, adaptive disability has utility as a marker for more
      severe and pervasive impairments in AHII children.

PMID- 9915657
TI  - State-of-the-art update and review: clinical trials of lipid-lowering agents.

PMID- 9915658
TI  - Effect of niacin on atherosclerotic cardiovascular disease.
AB  - Niacin has been studied in 6 major clinical trials with cardiovascular endpoints.
      The Coronary Drug Project (CDP) was the largest of these trials and the only one
      to use niacin monotherapy affecting cardiovascular outcomes: recurrent myocardial
      infarction and cerebrovascular events were significantly decreased. After long
      term (15 years) follow-up, total mortality was also found to be decreased. The
      other 5 trials used varying combinations of niacin with other pharmacologic
      agents, examining coronary and total mortality, coronary events, and angiographic
      progression/regression. Significant benefit was found in all trials except for
      one in patients with normal cholesterol levels at entry. Thus, the use of niacin
      to prevent or treat atherosclerotic cardiovascular disease is based on strong and
      consistent evidence from clinical trials.

PMID- 9915659
TI  - Clinical profiles of plain versus sustained-release niacin (Niaspan) and the
      physiologic rationale for nighttime dosing.
AB  - Niacin is the oldest and most versatile agent in use for the treatment of
      dyslipidemia. It has beneficial effects on low-density lipoprotein cholesterol;
      high-density lipoprotein cholesterol; the apolipoproteins B and A-I constituting
      these fractions; triglyceride; and lipoprotein(a). Together, these benefits lead
      to a diminished incidence of coronary artery disease among niacin users. The
      chief constraints against niacin use have been flushing, gastrointestinal
      discomfort, and metabolic effects including hepatotoxicity. Time-release niacin
      has been developed in part to limit flushing, and now a nighttime formulation
      (Niaspan) has been developed that assists in containing this untoward effect. In
      a pivotal metabolic study, bed-time administration of 1.5 g time-release niacin
      was shown to have the same beneficial effects as 1.5 g plain niacin in 3 divided
      doses and to be well tolerated. Previous studies suggest that bedtime niacin
      administration diminishes lipolysis and release of free fatty acids to the liver;
      this, in turn, leads to an abolition of the usual diurnal increase in plasma
      triglyceride, which may result in diminished formation and secretion of
      triglyceride in the very-low-density lipoprotein fraction.

PMID- 9915660
TI  - A new extended-release niacin (Niaspan): efficacy, tolerability, and safety in
      hypercholesterolemic patients.
AB  - Immediate-release niacin manifests beneficial effects in cardiovascular disease
      with respect to dyslipidemic states. It lowers low-density lipoprotein (LDL)
      cholesterol, triglycerides, lipoprotein(a), and apoprotein B; at the same time,
      it increases high-density lipoprotein (HDL) cholesterol, HDL2, and apoprotein A
      I. However, use of crystalline niacin has drawbacks: therapy requires multidose
      regimens, and side effects include flushing and pruritus. Slowing absorption with
      sustained-release formulations succeeds in decreasing flushing and increasing
      tolerance, but increases in hepatic enzyme levels have raised safety concerns. A
      new extended-release, once-daily formulation of niacin (Niaspan) shows promise in
      minimizing flushing while avoiding hepatotoxicity. A multicenter, randomized,
      double-blind clinical trial of Niaspan enrolled 122 patients with confirmed
      diagnosis of primary dyslipidemia (LDL cholesterol >4.14 mmol/L [160 mg/dL] and
      triglycerides <9 mmol/L [800 mg/dL]) into 3 treatment groups: (1) Niaspan 1,000
      mg/day; (2) Niaspan 2,000 mg/day; and (3) placebo. The primary treatment endpoint
      was LDL-cholesterol level. This endpoint was not significantly affected by
      placebo (0.2% increase), but Niaspan decreased LDL cholesterol by 5.8% (1,000
      mg/day) and 14.6% (2,000 mg/day) (p <0.001). Likewise, with placebo there were
      significant changes in total cholesterol, triglycerides, lipoprotein(a), and
      apoprotein B, whereas both Niaspan 1,000 and 2,000 mg/day significantly (p
      <0.001) decreased these parameters. In addition, both Niaspan groups showed
      significant (p <0.001) increases in HDL cholesterol (17% and 23%, respectively),
      including HDL subfractions. With respect to flushing, 20% of the placebo group
      reported at least 1 episode, whereas 88% and 83% of the Niaspon 1,000- and 2,000
      mg/day groups, respectively, reported episodes. There was no hepatotoxicity as
      liver enzyme levels remained within clinically accepted limits in all treatment
      groups. However, Niaspan 2,000 mg/day showed a significant increase in aspartate
      aminotransferase compared with baseline and placebo. This trial demonstrated a
      cholesterol-modifying effect of Niaspan consistent with those reported for
      niacin, but demonstrated a better tolerance for flushing. Moreover, in contrast
      to sustained-release formulations, Niaspan showed relatively mild hepatic
      effects.

PMID- 9915661
TI  - Clinical trial experience with extended-release niacin (Niaspan): dose-escalation
      study.
AB  - Niacin is a useful lipid-modifying drug because it (1) decreases low-density
      lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and
      lipoprotein(a), and (2) raises high-density lipoprotein (HDL) cholesterol. Its
      use tends to be limited by side effects and inconvenient dosing regimens. The
      availability of an extended-release preparation (Niaspan-which has safety and
      efficacy similar to immediate-release niacin but which can be given once a day)
      provides an opportunity to increase the use of this effective lipid-modifying
      agent. To study the safety and efficacy of escalating doses of extended-release
      niacin, hyperlipidemic patients were randomly assigned to placebo or Niaspan. A
      forced dose-titration was done with the dosage increasing by 500 mg every 4 weeks
      to a maximum of 3,000 mg/day. Niaspan showed dose-related changes in total, LDL,
      and HDL cholesterol levels, triglycerides, cholesterol/HDL ratio, and
      lipoprotein(a). At a dosage of 2,000 mg/day, total cholesterol decreased by
      12.1%, LDL cholesterol by 16.7%, triglycerides by 34.5%, and lipoprotein(a) by
      23.6%; HDL cholesterol increased by 25.8%. Flushing was the most commonly
      reported side effect; flushing episodes tended to decrease with time despite an
      increasing dose of niacin. Of the reported side effects, only pruritus and rash
      were significantly different between the 2 groups. Aspartate aminotransferase,
      lactate dehydrogenase, and uric acid increased in a dose-dependent fashion, but
      fasting blood sugar increased by about 5% across most dosages. Two subjects had
      aspartate aminotransferase levels greater than twice the upper limit of normal,
      but there were no subjects in whom transaminases increased to 3 times the upper
      limit of normal. Women tended to have a greater LDL cholesterol response to the
      medication and also experienced more side effects, especially at higher dosages.
      Thus, the use of lower dosages of niacin may be desirable in women. The results
      of this dose-escalation study show beneficial effects of Niaspan on the entire
      lipid profile. At the maximum recommended dosage of 2,000 mg/day, all lipid and
      lipoprotein levels changed in desirable directions. Side effects (other than
      flushing) and blood chemistries were comparable to those seen with immediate
      release niacin.

PMID- 9915662
TI  - Mechanistic studies of high-density lipoproteins.
AB  - There is increasing evidence that high-density lipoprotein (HDL) and its
      subfractions are protective against atherosclerotic cardiovascular disease.
      Physical exercise, weight reduction, smoking cessation, diabetes mellitus
      control, and specific drugs, including niacin, fibrates, and estrogens, are
      effective methods to increase HDL levels. Niacin is the oldest and most powerful
      clinical agent for raising HDL levels. Niaspan, an extended-release niacin
      formulation, is as potent as immediate-release niacin in increasing levels of HDL
      cholesterol; subfractions HDL2 and HDL3; apolipoprotein A-I, the major protein of
      HDL, and its cardioprotective subfraction lipoprotein A-I. Recent research from
      our laboratory suggests a novel mechanism by which niacin inhibits hepatic
      removal of HDL-apoprotein A-I without interfering with the removal of cholesterol
      carried by HDL, thus augmenting reverse cholesterol transport. Other mechanistic
      studies indicate that fibrates and estrogens stimulate the synthesis and
      production of HDL-apoprotein A-I. Because niacin decreases HDL-apoprotein A-I
      removal, and fibrates and estrogens increase HDL-apoprotein A-I production,
      combinations of niacin with these agents may raise HDL levels more than fibrates
      or estrogens alone.

PMID- 9915663
TI  - Triglycerides as a risk factor for coronary artery disease.
AB  - Triglyceride has not traditionally been considered the cornerstone of lipid risk
      factors for coronary artery disease. Yet emerging evidence from epidemiologic,
      clinical, cellular, genetic, and molecular studies suggests otherwise, namely,
      that levels of triglyceride and triglyceride-rich lipoproteins such as very-low
      density lipoprotein (VLDL) are indeed independent risk factors for coronary
      artery disease. Further, triglyceride metabolism is associated with
      atherogenesis, and diminishing triglyceride levels is pivotal in decreasing the
      incidence of coronary artery disease, particularly in early-evolving
      atherosclerotic lesions.

PMID- 9915664
TI  - Lipoprotein(a) as a risk factor for coronary artery disease.
AB  - Since its identification by Kare Berg in 1963, lipoprotein(a) [Lp(a)] has become
      a focus of research interest owing to the results of case-control and prospective
      studies linking elevated plasma levels of this lipoprotein with the development
      of coronary artery disease. Lp(a) contains a low-density lipoprotein (LDL)-like
      moiety, in which the apolipoprotein B-100 component is covalently linked to the
      unique glycoprotein apolipoprotein(a) [apo(a)]. Apo(a) is composed of repeated
      loop-shaped units called kringles, the sequences of which are highly similar to a
      kringle motif present in the fibrinolytic proenzyme plasminogen. Variability in
      the number of repeated kringle units in the apo(a) molecule gives rise to
      different-sized Lp(a) isoforms in the population. Based on the similarity of
      Lp(a) to both LDL and plasminogen, it has been hypothesized that the function of
      this unique lipoprotein may represent a link between the fields of
      atherosclerosis and thrombosis. However, determination of the function of Lp(a)
      in vivo remains elusive. Although Lp(a) has been shown to accumulate in
      atherosclerotic lesions, its contribution to the development of atheromas is
      unclear. This uncertainty is related in part to the structural complexity of the
      apo(a) component of Lp(a) (particularly apo(a) isoform size heterogeneity), which
      also poses a challenge for standardization of the measurement of Lp(a) in plasma.
      The fact that plasma Lp(a) levels are largely genetically determined and vary
      widely among different ethnic groups adds scientific interest to the ongoing
      study of this enigmatic particle. Most recently, the identification of
      proteolytic fragments of apo(a) in both plasma and urine has fueled speculation
      about the origin of these fragments and their possible function in the
      atherosclerotic process.

PMID- 9915665
TI  - Diabetic dyslipidemia.
AB  - Usual risk factors for coronary artery disease account for only 25-50% of
      increased atherosclerotic risk in diabetes mellitus. Other obvious risk factors
      are hyperglycemia and dyslipidemia. However, hyperglycemia is a very late stage
      in the sequence of events from insulin resistance to frank diabetes, whereas
      lipoprotein abnormalities are manifested during the largely asymptomatic diabetic
      prodrome and contribute substantially to the increased risk of macrovascular
      disease. The insulin-resistant diabetes course affects virtually all lipids and
      lipoproteins. Chylomicron and very-low-density lipoprotein (VLDL) remnants
      accumulate, and triglycerides enrich high-density lipoprotein (HDL) and low
      density lipoprotein (LDL), leading to high levels of potentially atherogenic
      particles and low levels of HDL cholesterol. Hyperglycemia eventually impairs
      removal of triglyceride-rich lipoproteins, the accumulation of which accentuates
      hypertriglyceridemia. As triglycerides increase-still within the so-called normal
      range-abnormalities in HDL and LDL became more apparent. Thus, when triglycerides
      are >200 mg/dL, LDL particles are small and dense (when they are <90 mg/dL, the
      particles are of the large, buoyant variety). The atherogenicity of small, dense
      LDL particles is attributed to their increased susceptibility to oxidation, but
      in many patients they may be a marker for insulin resistance or the presence of
      atherogenic VLDL. Hypertriglyceridemia is associated with atherosclerosis because
      (1) it is a marker for insulin resistance and atherogenic metabolic
      abnormalities; and (2) the small size of triglyceride-enriched lipoproteins
      enables them to infiltrate the blood vessel wall where they are oxidized, bind to
      receptors on macrophages, and ingested, leading to the development of the
      atherosclerotic lesion. Various studies (primary prevention with gemfibrozil:
      Helsinki Heart Study; secondary prevention with simvastatin and pravastatin:
      Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events
      [CARE], respectively) have demonstrated that lipid-lowering therapy in type 2
      diabetes is effective in decreasing the number of cardiac events. Risk reduction
      was 22% to 50% (statins) and approximately 65% (fibrate) relative to placebo. It
      was also noted (in 4S and CARE) that the risk of major coronary events in
      untreated diabetic patients was 1.5-1.7-fold greater than in untreated
      nondiabetic patients. Although gemfibrozil (fibric acid derivative) is more
      effective in decreasing triglycerides and increasing HDL cholesterol in diabetic
      patients than the statins, it does not change and may even increase LDL
      cholesterol levels (fenofibrate may be an exception, decreasing LDL cholesterol
      by 20-25% in some studies). However, gemfibrozil does increase LDL particle size.
      Nevertheless, the statins are the current lipid-lowering drugs of choice because
      the change in LDL-cholesterol-to-HDL-cholesterol ratio is better than with
      gemfibrozil. Moreover, the diabetic patient may be more likely to benefit from
      statin therapy than the nondiabetic patient. It should be noted that, in theory,
      nicotinic acid can correct or improve all lipid or lipoprotein abnormalities in
      patients with type 2 diabetes. Unfortunately, it is relatively contraindicated
      because it causes insulin resistance and may precipitate or aggravate
      hyperglycemia (in addition to its other well-known side effects such as flushing,
      gastric irritation, development of hepatotoxicity, and hyperuricemia). It is
      unknown at present whether newer formulations such as once-daily Niaspan may be
      better tolerated in diabetes. In any case, most patients with type 2 diabetes
      have risk factors for coronary artery disease and qualify for aggressive LDL
      cholesterol-lowering therapy. At the same time, it is presently unknown whether
      improved glycemic control decreases coronary artery disease risk in such
      patients.

PMID- 9915666
TI  - Efficacy and safety of an extended-release niacin (Niaspan): a long-term study.
AB  - Crystalline nicotinic acid (immediate-release niacin) is effective therapy for
      lipoprotein regulation and cardiovascular risk reduction. However, inconvenient
      regimens and unpleasant side effects decrease compliance. Sustained-release
      formulations designed to circumvent these difficulties increase hepatotoxicity.
      Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily,
      extended-release form, has been found effective and safe in short-term trials.
      The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517
      patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day.
      Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and
      apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were
      changes in total cholesterol, triglycerides, high-density lipoprotein (HDL)
      cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety
      data included adverse events and laboratory values over the 2-year study period.
      LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week
      96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96).
      Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only
      modest decreases in total cholesterol (12% and 13%, respectively), whereas total
      cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and
      lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and
      by 28% and 40%, respectively (week 96). All changes from baseline were
      significant (p <0.001). Niaspan was generally well tolerated, although flushing
      was common (75%); however, there was a progressive decrease in flushing with time
      from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was
      used by one third of patients before Niaspan dosing to minimize flushing
      episodes. Although serious adverse events occurred in about 10% of patients, none
      were considered probably or definitely related to Niaspan. Adverse events in
      general varied widely, but their true relation to the study drug is difficult to
      ascertain without a placebo (control) group. No deaths occurred. There were
      statistically significant changes in hepatic transaminases, alkaline phosphatase,
      direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these
      changes were mostly small and are not likely to be biologically or clinically
      significant (the decrease in phosphorus is a new finding in niacin therapy). No
      myopathy was observed. Thus, this long-term study confirms the earlier short-term
      findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein
      regulation.

PMID- 9915667
TI  - Treatment of hyperlipidemia with combined niacin-statin regimens.
AB  - Combined use of niacin with a statin is an attractive option, since these types
      of medication have the best records in clinical trials for reduction in
      cardiovascular events and improvement in progression/regression of coronary
      lesions. In early use, the niacin-statin combination generated a few case reports
      documenting severe myopathy and rhabdomyolysis. Subsequent prospective trials in
      >400 patients, however, have not encountered myopathy. This experience includes
      165 patients who took a statin in combination with Niaspan, a new, extended
      release niacin administered once nightly. Hepatic toxicity with immediate-release
      niacin and with Niaspan used in combination with statins has been minimal.
      However, substantial transaminase elevations occurred with the use of a sustained
      release niacin (Nicobid) given twice daily. The niacin-statin treatment regimens
      gave augmented low-density lipoprotein (LDL)-cholesterol reduction along with
      favorable changes in high-density lipoprotein (HDL) cholesterol, lipoprotein(a),
      and triglycerides. This combination therapy can be used safely as long as (1)
      careful attention is given to niacin formulation and dosing; (2) liver functions
      are monitored; and (3) patients are educated to recognize symptoms of myopathy.
      However, special caution should apply to use of niacin in combination with high
      doses of statins, or with statins introduced into clinical practice in 1997 or
      later, since little experience has accumulated in these circumstances.

PMID- 9915668
TI  - The use of laser Doppler imaging as an aid in clinical management decision making
      in the treatment of vesicant burns.
AB  - Vesicants are a group of chemicals recognised, under the terms of the Chemical
      Weapons Convention, as potential chemical warfare agents whose prime effect on
      the skin is to cause burns and blistering. Experience of the clinical management
      of these injuries is not readily available and therefore an accurate assessment
      of the severity of the lesion and extent of tissue involvement is an important
      factor when determining the subsequent clinical management strategy for such
      lesions. This study was performed to assess the use of laser Doppler imaging
      (LDI) as a noninvasive means of assessing wound microvascular perfusion following
      challenge with the vesicant agents (sulphur mustard or lewisite) by comparing the
      images obtained with histopathological analysis of the lesion. Large white pigs
      were challenged with sulphur mustard (1.91 mg cm(-2)) or lewisite (0.3 mg.cm(-2))
      vapour for periods of up to 6 h At intervals of between 1 h and 7 days following
      vesicant challenge, LDI images were acquired and samples for routine
      histopathology were taken. The results from this study suggest that LDI was: (i)
      a simple, reproducible and noninvasive means of assessing changes in tissue
      perfusion, and hence tissue viability, in developing and healing vesicant burns;
      (ii) the LDI images correlates well with histopathological assessment of the
      resulting lesions and the technique was sufficiently sensitive enough to
      discriminate between skin lesions of different aetiology. These attributes
      suggest that LDI would be a useful investigative tool that could aid clinical
      management decision making in the early treatment of vesicant agent-induced skin
      burns.

PMID- 9915669
TI  - Specific inhibition of iNOS decreases the intestinal mucosal peroxynitrite level
      and improves the barrier function after thermal injury.
AB  - Failure of GI tract mucosa to act as a barrier against bacterial translocation
      (BT) has been proposed as a potential source of sepsis and subsequent multiple
      organ failure post thermal injury. Nitric oxide (NO) is an inorganic radical
      produced by NO synthase (NOS) from L-arginine. Gut mucosal constitutive NOS
      (cNOS) provides protection for itself. In contrast to cNOS, inducible NOS (iNOS)
      releases far greater amounts of NO, promotes oxidative reactions and is
      responsible for tissue injury. Peroxynitrite formed by the rapid reaction between
      superoxide and NO, is a toxic substance that contributes to tissue injury in a
      number of biological systems. This study was designed to investigate the effect
      of iNOS specific inhibitor S-methylisothiourea (SMT) on the postburn intestinal
      mucosal barrier function and the possible mechanism of SMT's action. Female SPF
      Sprague Dawley rats underwent 35% total body surface area (TBSA) or sham burn.
      Either SMT or the same volume of saline was given (5 mg/kg, i.p. q 12 h) for 2
      days to assess the effect of iNOS inhibition. On postburn day 2, the intestinal
      mucosal cNOS and iNOS activity were assayed by using Griess' reagent, the
      mesenteric lymph node (MLN), spleen and liver were collected and cultured for BT
      assay and the cellular localization of nitrotyrosine, a marker for peroxynitrite
      activity, was examined by immunostaining. After thermal injury in rats,
      administration of SMT for 2 days decreased the intestinal mucosal iNOS activity/
      tNOS activity ratio and the BT incidence. Nitrotyrosine immunostaining of the
      intestinal mucosa showed a decrease in the SMT-treated group. These findings
      suggest that SMT, a specific inhibitor for iNOS improves the barrier function
      after burn by suppression of the intestinal mucosal iNOS activity. The decrease
      in NO production resulted in decreased formation of peroxynitrite and
      subsequently decreased damage of mucosal tissue.

PMID- 9915670
TI  - Serial experimental and clinical studies on the pathogenesis of multiple organ
      dysfunction syndrome (MODS) in severe burns.
AB  - These serial clinical and experimental studies were designed to clarify the
      pathogenesis of postburn MODS. Both animal and clinical studies were performed.
      In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz
      catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were
      used as controls). The burned dogs were randomly divided into 4 groups: immediate
      infusion, delayed infusion, delayed fast infusion and delayed fast infusion
      combined with ginsenosides. All dogs were kept under constant barbiturate
      sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial
      respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase
      (SDH), organ water content as well as light and electron microscopy of visceral
      tissues were determined. In the clinical study, 61 patients with extensive deep
      burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha
      ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2,
      interleukin-1, total organ water content and pathological observations of
      visceral tissues from patients who died of MODS were carried out. Results
      demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and
      inhalation injury are three main causes of postburn death. All inflammatory
      mediators increased markedly in both animals and patients who sustained organ
      damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings
      suggested that ischemic damage and systemic inflammatory response syndrome (SIRS)
      initiated by mediators or cytokines might be important in the pathogenesis of
      postburn MODS.

PMID- 9915671
TI  - Crystalloids, colloids and kids: a review of paediatric burns in intensive care.
AB  - This is a retrospective review of all burns patients admitted to a paediatric
      intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and
      clinical course are presented. Ninety-eight new burns victims were admitted with
      a mortality rate of 10.2%, all in burns of greater than 25% body surface area
      (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients
      with burns greater than 5% BSA, 33 received the hospital-recommended colloid
      based resuscitation formula, 46 received a combination of crystalloids and
      colloids and in 6 patients the resuscitation regimen was not able to be
      determined. The aetiology, age distribution, sex ratio, severity of burns and
      length of stay in hospital did not alter significantly over the study period. The
      number of burns admissions to PICU increased, as did their duration of intubation
      and ICU stay. The hospital-recommended resuscitation formula consistently
      underestimated the fluid volume required for adequate resuscitation. No
      statistically significant difference in adverse effects was found between the
      resuscitation groups. This study is unable to recommend a definitive approach to
      the fluid resuscitation of burns shock in paediatrics and the best approach is
      one of meticulous fluid resuscitation titrated on clinical effect.

PMID- 9915672
TI  - Body habitus as a predictor of burn risk in children: do fat boys still get
      burned?
AB  - Previous research at this institute has demonstrated that heavy-for-age boys are
      more burn prone than their normal sized counterparts. As this study is now 26
      years old, we reexamined the anthropomorphic indices of 372 children admitted to
      one burn center between January 1991 and July 1997 to determine if this trend was
      still evident. Male children were over-represented in the < or =5th and >95th
      percentiles for both height (p < 0.001, p < 0.05) and weight (p < 0.01, p <
      0.001). Female children were over-represented in the < or =5th and > 95th
      percentiles for height (p < 0.01, p < 0.05). Twenty-eight percent of boys at or
      below the 5th percentile for weight were burned as a result of known or suspected
      intentional injury, compared to 5.9% of the entire pediatric burn population. (p
      < 0.0004). 'Fat boys' continue to be over-represented in the pediatric burn
      population. Additionally, in the more recent time period, boys at or below the
      5th percentile for height or weight and girls= < 5th percentile or >95th
      percentile for height are also over-represented. The increased frequency of burn
      injury in small-for-age children may reflect an increased risk of burn injury
      secondary to neglect or nonaccidental trauma.

PMID- 9915673
TI  - Epidemiology of childhood burns in the burn unit of Ain Shams University in
      Cairo, Egypt.
AB  - Childhood burns in Egypt are a significant problem, especially in families of low
      socioeconomic status. These families live in overcrowded flats, which lack proper
      hygiene and tend to use kerosene stoves, which lack any safety measures. Three
      hundred and five burned children presented to the burn unit of Ain Shams
      University over a 20 month period. Proportionately more boys than girls were
      injured. There was an increase in the incidence between the ages of 4 to 6 years.
      Scalds formed 56.7% of the cause of burns, while 38.6% were due to flame. In 3
      and 1.6% the cause of burn was electrical and chemical, respectively. 20 patients
      were victims of industrial accidents showing a major problem of entrance of
      children between 8-15 years of lower socioeconomic class into the labor force.
      87.2% of the patients had minor burns while 13 children (4.3%) died of the
      consequences of burns during the period of the study.

PMID- 9915675
TI  - Effect of small burn injury on physical, social and psychological health at 3-4
      months after discharge.
AB  - Comparatively little attention has been given to the impact of smaller burns
      (less than 20% body surface area) on patients' health status after their return
      to normal life. The objective of this study was to investigate patients' own
      assessment of their physical and psychological health 3-4 months after discharge
      from in-patient treatment. A postal survey was employed which utilised: (a)
      personal and employment status questions; (b) a short health status questionnaire
      which was developed for use with this group of patients; (c) the hospital anxiety
      and depression scale (HAD); (d) the impact of event scale (IES). The response
      rate to the survey was 71%. Physical and social function were reported to be
      affected at the follow-up point in a minority of patients. The greatest impact of
      the injury was on levels of anxiety and response to trauma-related stress, as
      measured by the HAD and IES instruments - almost one third of the responders (15
      patients) had clinically significant scores on either or both dimensions of the
      IES. Factors which may be associated with the response to trauma-related stress
      are discussed.

PMID- 9915674
TI  - Effect of growth hormone therapy in burn patients on conservative treatment.
AB  - Evaluation of growth hormone therapy in burns is limited and none is reported
      from developing countries where burns still carry high mortality. We analysed
      serial observations on the clinical and biochemical profiles in 13 patients with
      second and third degree burns who received recombinant human growth hormone
      (rhGH) (0.5 IU/kg body wt) for 2 weeks in addition to standard conservative
      treatment and in 9 patients who were managed with standard conservative treatment
      only. The two groups of patients had burns, comparable in extent and severity.
      Additional rhGH treatment resulted in improved wound healing (p < 0.001), delayed
      separation of eschars (p < 0.01), increase in haemoglobin (p < 0.05), serum
      albumin (p < 0.01), calcium (p < 0.05), phosphorus (p < 0.001), glomerular
      filtration rate (p < 0.05) and 7 fold elevation in IGF-1. Also, a reduction in
      weight loss (p < 0.01), nitrogen production rate (p < 0.05), catabolic index (p <
      0.01), duration of sepsis (p < 0.01) and hospital stay by 40% (p < 0.01) was
      noted with rhGH therapy. Transient hypercalcemia (3 patients), albuminuria (2
      patients) and elevated blood glucose (one patient) were noted in the rhGH treated
      group not necessitating any specific therapy. Mortality in rhGH treatment group
      was 8.3% compared to 44.5% in the "no rhGH" treatment group. These observations
      suggest significant benefits of short term rhGH treatment in burn patients on
      conservative management.

PMID- 9915677
TI  - A study of the concentration of orally administered sparfloxacin found in
      exudates from suture wounds beneath occlusive dressings.
AB  - The concentration of orally administered sparfloxacin (SPFX), an antimicrobial
      agent, in exudates from the suture wounds beneath occlusive dressings has been
      measured. Twenty-one patients who received oral therapy with 100 mg of SPFX prior
      to surgery and 200 mg/day of SPFX after surgery were studied. During the
      operations, the suture wounds were covered by occlusive film. 48h post-operation,
      wound exudates under the dressings were drawn and measured using high performance
      liquid chromatography. SPFX values were 0.801+/-0.340 microg/ml (mean+/-SD). The
      results suggest that wound exudates beneath the occlusive dressing have
      concentrations of SPFX high enough to prevent infection in most cases when
      administered orally.

PMID- 9915676
TI  - Procalcitonin--a sepsis parameter in severe burn injuries.
AB  - Procalcitonin (PCT) levels increase in patients with systemic infections; the
      highest levels have been found in sepsis. This study tested whether plasma
      procalcitonin level was related to sepsis, CRP, burn size, inhalation injury or
      mortality in severely burned patients over the entire clinical course. In 27
      patients with 51 (20-91)% TBSA, PCT was measured three times weekly from
      admission over the entire course of stay in a single ICU. Daily scoring by the
      "Baltimore Sepsis Scale" was performed. The patients were assigned to three
      groups depending on the clinical course and outcome: A = no septic complications,
      B = septic complications-survivors, C = septic complications non-survivors. PCT
      levels were elevated slightly at admission (mean 2.1 ng/ml) except in three
      patients who suffered electrical burns (mean 15.7 ng/ml). PCT peak levels
      correlated well with the Scoring values (r = 0.84) while CRP did not (r = 0.64).
      Peak PCT levels were significantly higher (p < 0.005) in septic patients (B and
      C) who averaged 49.8+/-76.9 ng/ml, than in non-septic patients (A) who averaged
      peak levels of 2.3+/-3.7 ng/ml. The highest PCT levels were found immediately
      before death (86.8+/-97 ng/ml). Seven patients had an inhalation injury 3rd
      degree. In these patients at 24 h postburn, there was no relationship between PCT
      levels and inhalation injury but during the later days postburn there were
      significant differences in PCT levels in patients with versus without inhalation
      injury. All patients with inhalation injury 3rd degree developed septic
      complications. There was no positive correlation between the PCT-admission-levels
      and the TBSA, but there was a positive correlation between the TBSA and the mean
      peak PCT levels during the later days postburn (r = 0.73; p < 0.05). The cut-off
      value of 3 ng/ ml we found reliable to indicate severe bacterial or fungal
      infection. PCT values over 10 ng/ml increasing over the following days were found
      only in life-threatening situations due to systemic infections. The individual
      course of PCT in one patient is more important than absolute values. PCT
      presented in this study as a useful diagnostic parameter in severely burned
      patients.

PMID- 9915678
TI  - Is there still a place for comfort care in severe burns.
AB  - Successive improvements in burn care have steadily increased the survivability of
      many major burn injuries, however for some patients with the most severe injuries
      comfort care rather than active resuscitation has been seen as the correct course
      of action. A survey of UK burn unit directors by postal questionnaire sought
      details of current practice regarding comfort care, the factors involved in the
      decision making process and their response to eight hypothetical case histories.
      An 84% response to the survey showed that units would, on average, actively
      resuscitate thirty-seven patients a year and administer comfort care three times
      per year. Opinion was often divided regarding the decision to resuscitate in the
      cases presented.

PMID- 9915679
TI  - Burn injuries during paint thinner sniffing.
AB  - Thinner sniffing is popular among school children in Asian countries because it
      is readily available at low cost. Besides its toxicity to major organs, thinner
      inhalation is associated with various burn accidents. Four teenagers were
      admitted to the Burns Unit of the Prince of Wales Hospital over the period of
      1996-1997. They sustained 3-25% TBSA flame burn and two of them had inhalation
      injuries as a result of the ignition of a cigarette during thinner sniffing. None
      of them had evidence of thinner intoxication as shown by blood tests. In the
      management of their acute burn injuries, their hidden social and family problems
      were explored. With the cooperation of different disciplines, early psychosocial
      intervention was given and their behavioral and psychological disturbances were
      successfully managed.

PMID- 9915680
TI  - Antibiotic prophylaxis--Hobson's choice in burns management.
AB  - Antibiotic prophylaxis is a routine procedure in management of burns. As such it
      is a safe practice, yet unusual complications can occur with the use of even
      safest antibiotics and their emergency management may be life saving. Here we
      present a case of 35% second and third degree burns who was taken for a second
      sitting of stamp grafting for remnant raw areas, who was administered
      intraoperative prophylactic antibiotic, developed a series of unusual
      complications sequentially, which were life threatening. Prompt recognition of
      signs and symptoms of adverse reactions of the drug used and timely management
      resulted in the successful outcome. A good team effort by surgeon, anaesthetist
      and the physician was mandatory.

PMID- 9915681
TI  - Profile of Kangari cancer: a prospecive study.
AB  - Kangari, an earthenware brazier containing burning charcoal, is used for personal
      warming during the winter months by most of the people in Kashmir valley. Kangari
      is usually held close to the lower abdomen or in between the legs while squatting
      on the ground. The use of kangari is associated with development of skin cancer
      at the sites of prolonged exposure. In the present study 43 patients with Kangari
      cancer were analyzed prospectively with the objective of understanding their
      clinico-pathological profile and the response to various treatment modalities.
      Variables such as age, gender, grade, site of lesion etc., were evaluated for
      their prognostic significance.

PMID- 9915682
TI  - Lymphedema of the lower extremity as a complication of local burns.
AB  - Lymphedema of an extremity is a rare complication of local burns, due to intact
      deep lymphatics. Here we present a case of delayed lymphedema of the foot,
      developing due to deep scarring after local burns.

PMID- 9915683
TI  - Use of Biobrane in pediatric scald burns--experience in 106 children by L.F. Ou,
      S.Y. Lee, Y.C. Chen, R.S. Yang, Y.W. Tang.

PMID- 9915684
TI  - Prevention of group B streptococci and Centers for Disease Control and Prevention
      compliance.

PMID- 9915691
TI  - Astrophysics on the GRAPE family of special-purpose computers 
AB  - The GRAPE-4, the world's fastest computer in 1995-1997, has produced some major
      scientific results through a wide diversity of large-scale simulations in
      astrophysics. Applications have included planetary formation, the evolution of
      star clusters and galactic nuclei, and the formation of galaxies and clusters of
      galaxies.

PMID- 9915692
TI  - Self-oriented regular arrays of carbon nanotubes and their field emission
      properties 
AB  - The synthesis of massive arrays of monodispersed carbon nanotubes that are self
      oriented on patterned porous silicon and plain silicon substrates is reported.
      The approach involves chemical vapor deposition, catalytic particle size control
      by substrate design, nanotube positioning by patterning, and nanotube self
      assembly for orientation. The mechanisms of nanotube growth and self-orientation
      are elucidated. The well-ordered nanotubes can be used as electron field emission
      arrays. Scaling up of the synthesis process should be entirely compatible with
      the existing semiconductor processes, and should allow the development of
      nanotube devices integrated into silicon technology.

PMID- 9915685
TI  - Ethical accountability and novel perinatal treatments.

PMID- 9915693
TI  - Pulmonary function and metabolic physiology of theropod dinosaurs 
AB  - Ultraviolet light analysis of a fossil of the theropod dinosaur Scipionyx
      samniticus revealed that the liver subdivided the visceral cavity into distinct
      anterior pleuropericardial and posterior abdominal regions. In addition,
      Scipionyx apparently had diaphragmatic musculature and a dorsally attached
      posterior colon. These features provide evidence that diaphragm-assisted lung
      ventilation was present in theropods and that these dinosaurs may have used a
      pattern of exercise physiology unlike that in any group of living tetrapods.

PMID- 9915694
TI  - An approximately 15,000-year record of El Nino-driven alluviation in southwestern
      ecuador 
AB  - Debris flows have deposited inorganic laminae in an alpine lake that is 75
      kilometers east of the Pacific Ocean, in Ecuador. These storm-induced events were
      dated by radiocarbon, and the age of laminae that are less than 200 years old
      matches the historic record of El Nino events. From about 15,000 to about 7000
      calendar years before the present, the periodicity of clastic deposition is
      greater than or equal to 15 years; thereafter, there is a progressive increase in
      frequency to periodicities of 2 to 8.5 years. This is the modern El Nino
      periodicity, which was established about 5000 calendar years before the present.
      This may reflect the onset of a steeper zonal sea surface temperature gradient,
      which was driven by enhanced trade winds.

PMID- 9915695
TI  - Nanophase-separated polymer films as high-performance antireflection coatings 
AB  - Optical surfaces coated with a thin layer to improve light transmission are
      ubiquitous in everyday optical applications as well as in industrial and
      scientific instruments. Discovered first in 1817 by Fraunhofer, the coating of
      lenses became standard practice in the 1930s. In spite of intensive research,
      broad-band antireflection coatings are still limited by the lack of materials
      with low refractive indices. A method based on the phase separation of a
      macromolecular liquid to generate nanoporous polymer films is demonstrated that
      creates surfaces with high optical transmission.

PMID- 9915697
TI  - Compensation of horizontal temperature and salinity gradients in the ocean mixed
      layer 
AB  - Establishment of the temperature-salinity relationship in the ocean has concerned
      oceanographers for decades because of its importance for understanding ocean
      circulation. High-resolution measurements in the ocean mixed layer are used to
      show that temperature and salinity gradients on horizontal scales of 20 meters to
      10 kilometers tend to compensate in their effect on density. These observations
      support the notion of a horizontal mixing in the mixed layer that depends on
      density gradient.

PMID- 9915696
TI  - Conversion of supramolecular clusters to macromolecular objects 
AB  - In a reaction proceeding within a nanoscopic volume, supramolecular clusters were
      transformed to polymer objects while retaining their shape and size. Spatial
      isolation of the cross-linkable blocks of oligobutadiene that were involved in
      this stitching reaction was achieved by self-assembly of the molecules that made
      up the clusters. Thermal activation of cross-linking yielded macromolecules
      (molecular weight of 70,000) with a narrow size distribution that was similar to
      that of the supramolecular clusters. The macromolecules obtained have an
      anisotropic shape (2 nanometers by 8 nanometers), as determined by electron
      microscopy and small-angle x-ray scattering, and form materials that exhibit a
      liquid crystalline state.

PMID- 9915698
TI  - Transient phase-induced nucleation 
AB  - A transient metastable rotator phase occurring on crystallization of hexadecane
      into its triclinic phase from the supercooled melt was directly observed with
      time-resolved synchrotron x-ray scattering. In this system, the limit of
      supercooling (the crystallization temperature) is determined by the thermodynamic
      stability of the transient phase with respect to the liquid. The crystallization
      kinetics of the homologous series of n-alkanes was measured and explained in
      terms of a crossover from stability to "long-lived" metastability to transient
      metastability. This crossover allowed further confirmation of the nature of the
      transient phase.

PMID- 9915699
TI  - Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution.
AB  - The origin of new morphological characters is a long-standing problem in
      evolutionary biology. Novelties arise through changes in development, but the
      nature of these changes is largely unknown. In butterflies, eyespots have evolved
      as new pattern elements that develop from special organizers called foci.
      Formation of these foci is associated with novel expression patterns of the
      Hedgehog signaling protein, its receptor Patched, the transcription factor
      Cubitus interruptus, and the engrailed target gene that break the conserved
      compartmental restrictions on this regulatory circuit in insect wings.
      Redeployment of preexisting regulatory circuits may be a general mechanism
      underlying the evolution of novelties.

PMID- 9915700
TI  - Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells
      in vivo.
AB  - Stem cells are found in various organs where they participate in tissue
      homeostasis by replacing differentiated cells lost to physiological turnover or
      injury. An investigation was performed to determine whether stem cells are
      restricted to produce specific cell types, namely, those from the tissue in which
      they reside. After transplantation into irradiated hosts, genetically labeled
      neural stem cells were found to produce a variety of blood cell types including
      myeloid and lymphoid cells as well as early hematopoietic cells. Thus, neural
      stem cells appear to have a wider differentiation potential than previously
      thought.

PMID- 9915701
TI  - A tobacco syntaxin with a role in hormonal control of guard cell ion channels.
AB  - The plant hormone abscisic acid (ABA) regulates potassium and chloride ion
      channels at the plasma membrane of guard cells, leading to stomatal closure that
      reduces transpirational water loss from the leaf. The tobacco Nt-SYR1 gene
      encodes a syntaxin that is associated with the plasma membrane. Syntaxins and
      related SNARE proteins aid intracellular vesicle trafficking, fusion, and
      secretion. Disrupting Nt-Syr1 function by cleavage with Clostridium botulinum
      type C toxin or competition with a soluble fragment of Nt-Syr1 prevents potassium
      and chloride ion channel response to ABA in guard cells and implicates Nt-Syr1 in
      an ABA-signaling cascade.

PMID- 9915702
TI  - Reciprocal inhibitory connections and network synchrony in the mammalian
      thalamus.
AB  - Neuronal rhythmic activities within thalamocortical circuits range from partially
      synchronous oscillations during normal sleep to hypersynchrony associated with
      absence epilepsy. It has been proposed that recurrent inhibition within the
      thalamic reticular nucleus serves to reduce synchrony and thus prevents seizures.
      Inhibition and synchrony in slices from mice devoid of the gamma-aminobutyric
      acid type-A (GABAA) receptor beta3 subunit were examined, because in rodent
      thalamus, beta3 is largely restricted to reticular nucleus. In beta3 knockout
      mice, GABAA-mediated inhibition was nearly abolished in reticular nucleus, but
      was unaffected in relay cells. In addition, oscillatory synchrony was
      dramatically intensified. Thus, recurrent inhibitory connections within reticular
      nucleus act as "desynchronizers."

PMID- 9915703
TI  - Prevention of constitutive TNF receptor 1 signaling by silencer of death domains.
AB  - Tumor necrosis factor receptor type 1 (TNF-R1) contains a cytoplasmic death
      domain that is required for the signaling of TNF activities such as apoptosis and
      nuclear factor kappa B (NF-kappaB) activation. Normally, these signals are
      generated only after TNF-induced receptor aggregation. However, TNF-R1 self
      associates and signals independently of ligand when overexpressed. This apparent
      paradox may be explained by silencer of death domains (SODD), a widely expressed
      approximately 60-kilodalton protein that was found to be associated with the
      death domain of TNF-R1. TNF treatment released SODD from TNF-R1, permitting the
      recruitment of proteins such as TRADD and TRAF2 to the active TNF-R1 signaling
      complex. SODD also interacted with death receptor-3 (DR3), another member of the
      TNF receptor superfamily. Thus, SODD association may be representative of a
      general mechanism for preventing spontaneous signaling by death domain-containing
      receptors.

PMID- 9915704
TI  - Silencing of genes flanking the P1 plasmid centromere.
AB  - Partition modules stabilize bacterial plasmids and chromosomes by actively
      promoting their segregation into daughter cells. The partition module of plasmid
      P1 is typical and consists of a centromere site, parS, and genes that encode
      proteins ParA and ParB. We show that ParB can silence genes flanking parS (to
      which ParB binds), apparently by polymerizing along the DNA from a nucleation
      site at parS. Wild-type ParB contacts an extensive region of P1 DNA; silencing
      defective ParB proteins, which were found to be partition-defective, are less
      able to spread. Hence, the silenced structure appears to function in
      partitioning.

PMID- 9915705
TI  - The role of locus coeruleus in the regulation of cognitive performance.
AB  - Noradrenergic locus coeruleus (LC) neurons were recorded in monkeys performing a
      visual discrimination task, and a computational model was developed addressing
      the role of the LC brain system in cognitive performance. Changes in spontaneous
      and stimulus-induced patterns of LC activity correlated closely with fluctuations
      in behavioral performance. The model explains these fluctuations in terms of
      changes in electrotonic coupling among LC neurons and predicts improved
      performance during epochs of high coupling and synchronized LC firing. Cross
      correlations of simultaneously recorded LC neurons confirmed this prediction,
      indicating that electrotonic coupling in LC may play an important role in
      attentional modulation and the regulation of goal-directed versus exploratory
      behaviors.

PMID- 9915706
TI  - Light-Gap disturbances, recruitment limitation, and tree diversity in a
      neotropical forest 
AB  - Light gap disturbances have been postulated to play a major role in maintaining
      tree diversity in species-rich tropical forests. This hypothesis was tested in
      more than 1200 gaps in a tropical forest in Panama over a 13-year period. Gaps
      increased seedling establishment and sapling densities, but this effect was
      nonspecific and broad-spectrum, and species richness per stem was identical in
      gaps and in nongap control sites. Spatial and temporal variation in the gap
      disturbance regime did not explain variation in species richness. The species
      composition of gaps was unpredictable even for pioneer tree species. Strong
      recruitment limitation appears to decouple the gap disturbance regime from
      control of tree diversity in this tropical forest.

PMID- 9915707
TI  - Preventing osteoporosis, falls, and fractures among elderly people. Promotion of
      lifelong physical activity is essential.

PMID- 9915708
TI  - Who should take responsibility for antisocial personality disorder? Fallon
      suggests emphasising custody, but psychiatrists' future role remains unclear.

PMID- 9915709
TI  - Microalbuminuria as predictor of outcome. Shows promise but large prospective
      trials are needed.

PMID- 9915710
TI  - Di Bella's therapy: the last word? The evidence would be stronger if the
      researchers had randomised their studies.

PMID- 9915711
TI  - The NHS: possibilities for the endgame. Think more about reducing expectations.

PMID- 9915712
TI  - The firing of brother George. The AMA has damaged itself by sacking JAMA's
      editor.

PMID- 9915713
TI  - Ashworth report confirms problems with special hospitals.

PMID- 9915714
TI  - In brief 

PMID- 9915715
TI  - WHO budget set to reflect new priorities.

PMID- 9915716
TI  - Ritalin may influence serotonin balance in hyperactive children 

PMID- 9915717
TI  - JAMA's editor fired over sex article.

PMID- 9915718
TI  - UK study reveals double the risk of ill health in gulf war veterans 

PMID- 9915719
TI  - Intestinal worms impair child health in the Philippines.

PMID- 9915721
TI  - Scottish doctors launch their manifesto.

PMID- 9915720
TI  - US doctors file lawsuit against antiabortionists.

PMID- 9915722
TI  - New variantCJD found in tonsils 

PMID- 9915723
TI  - Wales to reform psychiatric care for children.

PMID- 9915724
TI  - US Congress debates stem cell research.

PMID- 9915726
TI  - Prophylactic mastectomy cuts breast cancer risk 

PMID- 9915725
TI  - Endocrine disorders remain undetected and untreated in India.

PMID- 9915727
TI  - Conservatives blame rationing for winter crisis.

PMID- 9915728
TI  - Is there a rationale for rationing chronic dialysis? A hospital based cohort
      study of factors affecting survival and morbidity.
AB  - OBJECTIVES: To determine factors influencing survival and need for
      hospitalisation in patients needing dialysis, and to define the potential basis
      for rationing access to renal replacement therapy. DESIGN: Hospital based cohort
      study of all patients starting dialysis over a 4 year recruitment period (follow
      up 15-63 months). Groups were defined on the basis of age, comorbidity,
      functional status, and whether dialysis initiation was planned or unplanned.
      SETTING: Renal unit in a district general hospital, which acts as the main renal
      referral centre for four other such hospitals and serves a population of about
      1.15 million people. SUBJECTS: 292 patients, mean age 61.3 years (18-92 years, SD
      15.8), of whom 193 (66%) were male, and 59 (20%) were patients with diabetes.
      Dialysis initiation was planned in 163 (56%) patients and unplanned in 129 (44%).
      MAIN OUTCOME MEASURES: Overall survival, 1 year survival, and hospitalisation
      rate. RESULTS: Factors affecting survival in the Cox's proportional hazard model
      were Karnofsky performance score at presentation (hazard ratio 0.979, 95%
      confidence interval 0.972 to 0. 986), comorbidity severity score (1.240, 1.131 to
      1.340), age (1.036, 1.018 to 1.054), and myeloma (2.15, 1.140 to 4.042). The
      Karnofsky performance score used 3 months before presentation was significant
      (0.970, 0.956 to 0.981), as was unplanned presentation in this model (1.796,
      1.233 to 2.617). Using these factors, a high risk group of 26 patients was
      defined, with 19.2% 1 year survival. Denying dialysis to this group would save
      3.2% of the total cost of the chronic programme but would sacrifice five long
      term survivors. Less rigorous definition of the high risk group would save more
      money but lose more long term survivors. CONCLUSIONS: Severity of comorbid
      conditions and functional capacity are more important than age in predicting
      survival and morbidity of patients on dialysis. Late referral for dialysis
      affects survival adversely. Denial of dialysis to patients in an extremely high
      risk group, defined by a new stratification based on logistic regression, would
      be of debatable benefit.

PMID- 9915729
TI  - Evaluation of an unconventional cancer treatment (the Di Bella multitherapy):
      results of phase II trials in Italy. Italian Study Group for the Di Bella
      Multitherapy Trails.
AB  - OBJECTIVE: To determine whether the treatment known as Di Bella multitherapy
      exerts antitumour activity worthy of further controlled clinical evaluation.
      DESIGN: 11 independent multicentre uncontrolled phase II trials relevant to 8
      different types of cancer. SETTING: 26 Italian hospitals specialising in cancer
      treatment. SUBJECTS: 386 patients with advanced cancer were enrolled in the
      trials between March and July 1998 and followed to 31 October 1998.
      INTERVENTIONS: Melatonin, bromocriptine, either somatostatin or octreotide, and
      retinoid solution, the drugs that constitute Di Bella multitherapy, were given to
      patients daily. Cyclophosphamide and hydroxyurea were added in some trials. MAIN
      OUTCOME MEASURES: Responses were assessed every 1, 2, or 3 months, depending on
      the specific trial, and toxicity was evaluated using criteria developed by the
      World Health Organisation. RESULTS: No patient showed complete remission. Three
      patients showed partial remission: 1 of the 32 patients with non-Hodgkin's
      lymphoma; 1 of the 33 patients with breast cancer; and 1 of the 29 patients with
      pancreatic cancer. At the second examination, 12% (47) of the patients had stable
      disease; 52% (199) progressed; and 25% (97) died. CONCLUSIONS: Di Bella
      multitherapy did not show sufficient efficacy in patients with advanced cancer to
      warrant further clinical testing.

PMID- 9915730
TI  - Workplace bullying in NHS community trust: staff questionnaire survey.
AB  - OBJECTIVES: To determine the prevalence of workplace bullying in an NHS community
      trust; to examine the association between bullying and occupational health
      outcomes; and to investigate the relation between support at work and bullying.
      DESIGN: Questionnaire survey. SETTING: NHS community trust in the south east of
      England. SUBJECTS: Trust employees. MAIN OUTCOME MEASURES: Measures included a 20
      item inventory of bullying behaviours designed for the study, the job induced
      stress scale, the hospital anxiety and depression scale, the overall job
      satisfaction scale, the support at work scale, and the propensity to leave scale.
      RESULTS: 1100 employees returned questionnaires-a response rate of 70%. 421 (38%)
      employees reported experiencing one or more types of bullying in the previous
      year. 460 (42%) had witnessed the bullying of others. When bullying occurred it
      was most likely to be by a manager. Two thirds of the victims of bullying had
      tried to take action when the bullying occurred, but most were dissatisfied with
      the outcome. Staff who had been bullied had significantly lower levels of job
      satisfaction (mean 10.5 (SD 2. 7) v 12.2 (2.3), P<0.001) and higher levels of job
      induced stress (mean 22.5 (SD 6.1) v 16.9 (5.8), P<0.001), depression (8% (33) v
      1% (7), P<0.001), anxiety (30% (125) v 9% (60), P<0.001), and intention to leave
      the job (8.5 (2.9) v 7.0 (2.7), P<0.001). Support at work seemed to protect
      people from some of the damaging effects of bullying. CONCLUSIONS: Bullying is a
      serious problem. Setting up systems for supporting staff and for dealing with
      interpersonal conflict may have benefits for both employers and staff.

PMID- 9915732
TI  - Long term follow up 

PMID- 9915731
TI  - Observational study of defibrillation in theatre.

PMID- 9915734
TI  - Not what he wanted 

PMID- 9915733
TI  - Questionnaire study and audit of use of angiotensin converting enzyme inhibitor
      and monitoring in general practice: the need for guidelines to prevent renal
      failure.
AB  - OBJECTIVES: To determine the current pattern of use of angiotensin converting
      enzyme inhibitor and monitoring of renal function in general practice and to
      audit all admissions to a regional renal unit for uraemia related to use of these
      drugs. DESIGN: Postal questionnaire sent to 400 general practitioners; audit of
      clinical notes of all patients receiving these drugs in one large general
      practice; audit of all cases of uraemia (creatinine concentration >500
      micromol/l) related to treatment presenting to hospital renal services over 12
      months. SETTING: General practices in the North Wales health authority and one in
      central Manchester. Regional renal unit in Salford. MAIN OUTCOME MEASURES:
      Proportion of general practitioners who regularly monitored renal function before
      and after initiation of angiotensin converting enzyme inhibitors. Indications for
      treatment and details of monitoring of renal function in patients receiving these
      drugs. Incidence of related uraemia and evidence of comorbid disease, other
      aetiological factors, delayed detection, and patient outcome. RESULTS: 277 (69%)
      general practitioners replied; 235 (85%) checked renal function before but only
      93 (34%) after the start of treatment, and 42 (15%) never checked renal function.
      Angiotensin converting enzyme inhibitors were prescribed for 162 patients from a
      total of 3625 aged >35 years (mean age 66.4 (SD 15.9) years). Monitoring of renal
      function occurred before treatment in 55 (45%) and after start of treatment in 35
      (29%) of the 122 patients treated in general practice. Angiotensin converting
      enzyme inhibitors could be causally implicated in 9 (7%) of 135 admissions for
      uraemia (mean age 74.2 (7. 2) v 62.1 (2.1) years; P<0.01). 3 patients had
      renovascular disease and 6 had congestive cardiac failure with another
      intercurrent illness. Renal function had not been checked in any patient after
      the start of treatment; mean duration of illness before admission was 10.5 (3.2)
      days. Mean length of hospital stay was 20.9 (10.4) days; there were 8 survivors.
      CONCLUSION: Cases of uraemia related to treatment with angiotensin converting
      enzyme inhibitors are still encountered and are often detected late because of
      lack of judicious monitoring of renal function in vulnerable, often elderly,
      patients, especially at times of intercurrent illness. Guidelines for appropriate
      monitoring of renal function may help to minimise the problem.

PMID- 9915736
TI  - The country matters 

PMID- 9915737
TI  - ABC of sexual health: male sexual problems.

PMID- 9915735
TI  - Fortnightly review: anticoagulation in heart disease.

PMID- 9915738
TI  - Shared ethical principles for everybody in health care: a working draft from the
      Tavistock group.

PMID- 9915739
TI  - Professional and public attitudes towards unsolicited medical intervention.

PMID- 9915740
TI  - Narrative based medicine: narrative in medical ethics.

PMID- 9915741
TI  - A memorable incident: when a spade is not a spade.

PMID- 9915742
TI  - Taking precautions with angiotensin converting enzyme inhibitors. Angiotensin
      converting enzyme inhibitors are not proved to cause loss of renal mass.

PMID- 9915743
TI  - Clinicians should be proactive in testing for asthma.

PMID- 9915744
TI  - Methods used for suicide vary between regions in the developing world.

PMID- 9915745
TI  - Association between birth weight and death from heart disease. Data do not
      support association.

PMID- 9915746
TI  - Should industry sponsor research? Researchers must recognise damage done by overt
      association with formula manufacturers.

PMID- 9915747
TI  - Rescue thrombolysis for failure of primary thrombolysis cannot be justified.

PMID- 9915748
TI  - Chiropractic for low back pain. Experts in both UK and US believe that
      chiropractic works.

PMID- 9915749
TI  - Randomised block design is more powerful than minimisation.

PMID- 9915750
TI  - Identification of patients with atrial fibrillation in general practice.

PMID- 9915751
TI  - Potential collaborators saw various problems with study of detoxification under
      anaesthesia.

PMID- 9915752
TI  - Doctors don't see enough peaceful deaths.

PMID- 9915753
TI  - Vernon frederick ("Sam") hall 

PMID- 9915754
TI  - Suspension unfair to doctors, say peers 

PMID- 9915755
TI  - Too much medicine? 

PMID- 9915756
TI  - Di bella: the man, the cure, a hope for All 

PMID- 9915757
TI  - Trial by video: Someone to watch over me, ITV, 12 January.

PMID- 9915758
TI  - Website of the week 

PMID- 9915759
TI  - Crisis, what crisis? 

PMID- 9915760
TI  - Ashworth revisited 

PMID- 9915762
TI  - Four difficult questions 

PMID- 9915761
TI  - Good news is no news 

PMID- 9915763
TI  - Rationing dialysis on age alone is unjustified 

PMID- 9915764
TI  - Di bella multitherapy does not reduce tumour size 

PMID- 9915765
TI  - Bullying is common in NHS trust 

PMID- 9915766
TI  - Better guidelines are needed for monitoring of renal function during ACE
      inhibitor treatment 

PMID- 9915767
TI  - Doctors in theatre do not mange defibrillation well 

PMID- 9915768
TI  - Doctors are more wary than lay people of letting medicine invade everyday life 

PMID- 9915769
TI  - Cardiac troponin I gene knockout: a mouse model of myocardial troponin I
      deficiency.
AB  - Troponin I is a subunit of the thin filament-associated troponin-tropomyosin
      complex involved in calcium regulation of skeletal and cardiac muscle
      contraction. We deleted the cardiac isoform of troponin I by using gene targeting
      in murine embryonic stem cells to determine the developmental and physiological
      effects of the absence of this regulatory protein. Mice lacking cardiac troponin
      I were born healthy, with normal heart and body weight, because a fetal troponin
      I isoform (identical to slow skeletal troponin I) compensated for the absence of
      cardiac troponin I. Compensation was only temporary, however, as 15 days after
      birth slow skeletal troponin I expression began a steady decline, giving rise to
      a troponin I deficiency. Mice died of acute heart failure on day 18,
      demonstrating that some form of troponin I is required for normal cardiac
      function and survival. Ventricular myocytes isolated from these troponin I
      depleted hearts displayed shortened sarcomeres and elevated resting tension
      measured under relaxing conditions and had a reduced myofilament Ca sensitivity
      under activating conditions. The results show that (1) developmental
      downregulation of slow skeletal troponin I occurs even in the absence of cardiac
      troponin I and (2) the resultant troponin I depletion alters specific mechanical
      properties of myocardium and can lead to a lethal form of acute heart failure.

PMID- 9915770
TI  - Troponin I degradation and covalent complex formation accompanies myocardial
      ischemia/reperfusion injury.
AB  - Selective troponin I (TnI) modification has been demonstrated to be in part
      responsible for the contractile dysfunction observed with myocardial
      ischemia/reperfusion injury. We have isolated and characterized modified TnI
      products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed
      by 45 minutes of reperfusion using affinity chromatography with cardiac troponin
      C (TnC) and an anti-TnI antibody, immunological mapping, reversed-phase high
      performance liquid chromatography, and mass spectrometry. Rat cardiac TnI becomes
      progressively degraded from 210 amino acid residues to residues 1-193, 63-193,
      and 73-193 with increased severity of injury. Degradation is accompanied by
      formation of covalent complexes between TnI 1-193 and, respectively, TnC residues
      1-94 and troponin T (TnT) residues 191-298. The covalent complexes are likely a
      result of isopeptide bond formation between lysine 193 of TnI and glutamine 191
      of TnT by the cross-linking enzyme transglutaminase. With severe ischemia,
      cellular necrosis results in specific release of TnI 1-193 into the reperfusion
      effluent and TnT degradation in the myocardium (25-, 27-, and 33-kDa products).
      Two-dimensional electrophoresis demonstrated that phosphorylation of TnI prevents
      ischemia-induced degradation. This study characterized the modified TnI products
      in isolated rat hearts reperfused after a brief or severe period of ischemia,
      revealing the progressive nature of TnI degradation, changes in phosphorylation,
      and covalent complexes with ischemia/reperfusion injury. Finally, we propose a
      model for ischemia/reperfusion injury in which the extent of proteolytic and
      transglutaminase activities ultimately determines whether apoptosis or necrosis
      is achieved.

PMID- 9915771
TI  - Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak,
      and Bcl-x.
AB  - -Cytokine-induced NO production depresses myocardial contractility and has been
      shown to be cytotoxic to cardiac myocytes. However, the mechanisms of cytokine
      induced cardiac myocyte cell death are unclear. To analyze these mechanisms in
      detail, we treated neonatal cardiac myocytes in serum-free culture with a
      combination of the macrophage-derived cytokines interleukin-1beta, tumor necrosis
      factor-alpha, and interferon-gamma. These cytokines caused a time-dependent
      induction of cardiac myocyte apoptosis, but not necrosis, beginning 72 hours
      after treatment, as determined by nuclear morphology, DNA internucleosomal
      cleavage, and cleavage of poly(ADP-ribose) polymerase, reflecting caspase
      activation. Apoptosis was preceded by a >50-fold induction of inducible NO
      synthase mRNA and the release of large amounts (5 to 8 nmol/ microgram protein)
      of NO metabolites (NOx) into the medium. Cell death was completely blocked by an
      NO synthase inhibitor and attenuated by antioxidants (N-acetylcysteine and DTT)
      and the caspase inhibitor ZVAD-fmk. Cytokines also mediated an NO-dependent,
      sustained increase in myocyte expression of the Bcl-2 homologs Bak and Bcl-x(L).
      The NO donor S-nitrosoglutathione also induced apoptosis and cell levels of Bak,
      but not of Bcl-x(L). All effects of cytokines, including poly(ADP-ribose)
      polymerase cleavage, could be attributed to interleukin-1beta; interferon-gamma
      and tumor necrosis factor-alpha had no independent effects on apoptosis or on NOx
      production. We conclude that cytokine toxicity to neonatal cardiac myocytes
      results from the induction of NO and subsequent activation of apoptosis, at least
      in part through the generation of oxygen free radicals. The rate and extent of
      this apoptosis is modulated by alterations in the cellular balance of Bak and Bcl
      x(L), which respond differentially to cytokine-induced and exogenous NO and by
      the availability of oxidant species.

PMID- 9915772
TI  - Apoptosis of cardiac myocytes in Gsalpha transgenic mice.
AB  - -The stimulatory GTP-binding protein Gsalpha transmits signals from catecholamine
      receptors to activate adenylyl cyclase and thereby initiate a cascade leading to
      cardiac chronotropy and inotropy. Transgenic mice overexpressing the Gs alpha
      subunit (Gsalpha) selectively in their hearts exhibit increased cardiac
      contractility in response to beta-adrenergic receptor stimulation. However, with
      aging, these mice develop a cardiomyopathy. This study sought morphological and
      biochemical evidence that overexpression of Gsalpha is associated with increased
      myocyte apoptosis in the older animals and to determine whether such
      overexpression can promote apoptosis of isolated neonatal cardiac myocytes
      exposed to beta-adrenergic receptor agonists. In the hearts of 15- to 18-month
      old Gsalpha transgenic mice, histochemistry and electron microscopy illustrated
      the existence of numerous myocytes with abnormal nuclei embedded in collagen-rich
      connective tissue. Terminal deoxyribonucleotide transferase-mediated dUTP nick
      end labeling (TUNEL, for in situ labeling of DNA breaks) demonstrated that
      approximately 0.6% of myocyte nuclei contained fragmented DNA. Agarose gel
      electrophoresis provided further biochemical evidence of apoptosis by showing
      internucleosomal DNA fragmentation. Cultured cardiac myocytes from newborn
      Gsalpha transgenic mice showed increased TUNEL staining and internucleosomal DNA
      fragmentation compared with wild-type controls when treated with the beta-agonist
      isoproterenol. Thus, enhanced activation of beta-adrenergic signaling by
      overexpression of Gsalpha in the hearts of transgenic mice induces apoptosis of
      cardiac myocytes. This represents a potential mechanism that may contribute to
      the development of cardiomyopathy in this model.

PMID- 9915773
TI  - Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in
      murine cardiac myocytes.
AB  - -Transgenic mouse models have been developed to manipulate beta-adrenergic
      receptor (betaAR) signal transduction. Although several of these models have
      altered betaAR subtypes, the specific functional sequelae of betaAR stimulation
      in murine heart, particularly those of beta2-adrenergic receptor (beta2AR)
      stimulation, have not been characterized. In the present study, we investigated
      effects of beta2AR stimulation on contraction, [Ca2+]i transient, and L-type Ca2+
      currents (ICa) in single ventricular myocytes isolated from transgenic mice
      overexpressing human beta2AR (TG4 mice) and wild-type (WT) littermates. Baseline
      contractility of TG4 heart cells was increased by 3-fold relative to WT controls
      as a result of the presence of spontaneous beta2AR activation. In contrast,
      beta2AR stimulation by zinterol or isoproterenol plus a selective beta1
      adrenergic receptor (beta1AR) antagonist CGP 20712A failed to enhance the
      contractility in TG4 myocytes, and more surprisingly, beta2AR stimulation was
      also ineffective in increasing contractility in WT myocytes. Pertussis toxin
      (PTX) treatment fully rescued the ICa, [Ca2+]i, and contractile responses to
      beta2AR agonists in both WT and TG4 cells. The PTX-rescued murine cardiac beta2AR
      response is mediated by cAMP-dependent mechanisms, because it was totally blocked
      by the inhibitory cAMP analog Rp-cAMPS. These results suggest that PTX-sensitive
      G proteins are responsible for the unresponsiveness of mouse heart to agonist
      induced beta2AR stimulation. This was further corroborated by an increased
      incorporation of the photoreactive GTP analog [gamma-32P]GTP azidoanilide into
      alpha subunits of Gi2 and Gi3 after beta2AR stimulation by zinterol or
      isoproterenol plus the beta1AR blocker CGP 20712A. This effect to activate Gi
      proteins was abolished by a selective beta2AR blocker ICI 118,551 or by PTX
      treatment. Thus, we conclude that (1) beta2ARs in murine cardiac myocytes couple
      to concurrent Gs and Gi signaling, resulting in null inotropic response, unless
      the Gi signaling is inhibited; (2) as a special case, the lack of cardiac
      contractile response to beta2AR agonists in TG4 mice is not due to a saturation
      of cell contractility or of the cAMP signaling cascade but rather to an
      activation of beta2AR-coupled Gi proteins; and (3) spontaneous beta2AR activation
      may differ from agonist-stimulated beta2AR signaling.

PMID- 9915774
TI  - Nitric oxide-independent relaxations to acetylcholine and A23187 involve
      different routes of heterocellular communication. Role of Gap junctions and
      phospholipase A2.
AB  - NO- and prostanoid-independent relaxations are generally assumed to be mediated
      by an endothelium-derived hyperpolarizing factor (EDHF) that has been postulated
      to be an arachidonic acid metabolite. Recent evidence also suggests that direct
      heterocellular gap junctional communication (GJC) between endothelium and smooth
      muscle contributes to NO-independent relaxations. In the present study we have
      investigated the contribution of phospholipase A2 (PLA2)-linked metabolites and
      GJC to EDHF-type relaxations in rabbit mesenteric artery. In isolated rings
      preconstricted with 10 micromol/L phenylephrine in the presence of NG-nitro-L
      arginine methyl ester (L-NAME) and indomethacin, acetylcholine (ACh) and the Ca2+
      ionophore A23187 evoked relaxations that were markedly attenuated by the Ca2+
      dependent PLA2 inhibitors 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (3
      micromol/L) and arachidonyl trifluoromethyl ketone (3 micromol/L), but were
      potentiated by the sulfhydryl agent thimerosal (300 nmol/L). In intact rings,
      relaxations to ACh were attenuated synergistically by L-NAME and Gap 27 peptide,
      an inhibitor of GJC, whereas ACh-evoked relaxations of "sandwich" preparations
      were unaffected by the peptide but were abolished by L-NAME. In both ring and
      sandwich preparations A23187-induced relaxations were attenuated by inhibition of
      PLA2 but were insensitive to L-NAME and Gap 27 peptide. We conclude that EDHF
      type relaxations of rabbit mesenteric artery to ACh and A23187 depend on a common
      pathway that involves activation of PLA2. In the case of ACh, relaxation requires
      transfer of a factor or factors from the endothelium to smooth muscle via gap
      junctions, whereas A23187 permits release directly into the extracellular space.

PMID- 9915775
TI  - A high level of CCAAT-enhancer binding protein-delta expression is a major
      determinant for markedly elevated differential gene expression of the platelet
      derived growth factor-alpha receptor in vascular smooth muscle cells of
      genetically hypertensive rats.
AB  - -Platelet-derived growth factor-alpha receptor (PDGF-alphaR) expression is
      markedly elevated in cultured vascular smooth muscle cells (VSMCs) from
      spontaneously hypertensive rats (SHR) when compared with normotensive rat
      strains, Sprague-Dawley, Wistar, and Wistar-Kyoto rats (WKY). This "almost-all-or
      none" type of differential expression strongly suggests that PDGF-alphaR or its
      transcription-regulating mechanisms or factors are significantly related to
      genetic hypertension. To evaluate the role of PDGF-alphaR in vascular remodeling
      and hypertension, we have investigated the underlying molecular mechanism. We
      have recently shown that the regulatory domain responsible for this difference is
      localized to the PDGF-alphaR promoter region between -246 and -139, which
      contains an enhancer core sequence specific for CCAAT-enhancer binding proteins
      (C/EBPs). We defined the roles of this element for hypertensive strain-specific
      PDGF-alphaR gene transcription. DNA-protein binding studies by competition in
      electromobility shift and supershift assays revealed that 2 members, C/EBP-beta
      and C/EBP-delta, are mainly responsible for DNA-protein complex formation; the
      former acts as a transcriptional repressor and the latter as an activator of the
      PDGF-alphaR gene, respectively. Western or Northern blot analyses supported
      evidence for high expression of C/EBP-delta seen only in SHR-derived VSMCs.
      Furthermore, forced expression of C/EBP-delta transactivated the transcriptional
      efficiency of the PDGF-alphaR gene even in WKY-derived VSMCs, whereas that of
      C/EBP-beta had an opposite effect in SHR-derived VSMCs. These findings indicate
      that differential expression of members of the C/EBP family, mainly C/EBP-delta
      and possibly C/EBP-beta, are responsible for the strain-specific gene
      transcription of PDGF-alphaR in VSMCs.

PMID- 9915776
TI  - Heparin proteoglycans released from rat serosal mast cells inhibit proliferation
      of rat aortic smooth muscle cells in culture.
AB  - -Mast cells are present in the human arterial intima. To study whether mast-cell
      degranulation influences the rate of proliferation of smooth muscle cells, we
      cocultured sensitized (IgE-bearing) rat serosal mast cells and rat aortic smooth
      muscle cells (SMCs). When sensitized mast cells were stimulated to degranulate
      with antigen, the rate of proliferation of the cocultured SMCs decreased sharply.
      This inhibitory effect was found to be due mainly to the very high molecular
      weight (Mr) heparin proteoglycans (average Mr 750 000) released from the
      stimulated mast cells. When the heparin proteoglycans were purified from mast
      cell granule remnants and added to the SMC culture, they were found to block the
      cell cycle at the G0-->S transition and the exit from the G2/M phase, their
      inhibitory effect resembling that of commercial heparin. However, in contrast to
      the reported dependence of the inhibitory effect of commercial heparin on the
      release of transforming growth factor-beta from serum, the inhibitory effect of
      the mast cell-derived heparin proteoglycans in the presence of serum was not
      transforming growth factor-beta dependent. Moreover, the effect of the mast cell
      derived heparin proteoglycans was more efficient than that of commercial heparins
      of high (average Mr 15 000) and low (average Mr 5000) molecular weight. We also
      purified heparin glycosaminoglycans (average Mr 75 000) from the mast cell
      derived heparin proteoglycans and found that they also inhibited SMC growth
      efficiently, although less strongly than their parent heparin proteoglycans.
      These results reveal, for the first time, that mast cells are able to regulate
      SMC growth. Thus, activated mast cells, by releasing heparin proteoglycans,
      possibly participate in the regulation of SMC growth in the human arterial
      intima, the site of atherogenesis.

PMID- 9915777
TI  - Local overexpression of thrombomodulin for in vivo prevention of arterial
      thrombosis in a rabbit model.
AB  - -Endothelial thrombomodulin plays a critical role in hemostasis by binding
      thrombin and subsequently converting protein C to its active form, a powerful
      anticoagulant. Thrombomodulin thus represents a central mechanism by which
      patency is maintained in normal vessels. However, thrombomodulin expression
      decreases in perturbed endothelial cells, predisposing to thrombotic occlusion.
      An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and
      functionally characterized in vitro and in vivo. The impact of local
      overexpression of thrombomodulin on in vivo thrombus formation was subsequently
      examined in a stasis/injury model of arterial thrombosis. The construct prevented
      arterial thrombosis formation in all animals, while viral and nonviral controls
      typically developed occluding thrombi. By histological analysis, nonviral
      controls exhibited intravascular thrombus occluding a mean of 70.52+/-3.72% of
      available lumen, while viral controls reached 86. 85+/-2.82% thrombotic
      occlusion; in contrast, Adv/RSV-THM reduced thrombosis to 28.61+/-3.31% of lumen
      in cross section. No significant intima-to-media ratio was observed in the
      thrombomodulin group relative to controls. Local infiltration of granulocytes and
      macrophages significantly decreased in the Adv/RSV-THM group relative to
      controls, while neutrophilic infiltration increased in viral controls relative to
      nonviral controls. This construct thus offers a viable technique for promoting a
      locally thromboresistant small-caliber artery, without the inflammatory damage
      that has limited many other adenoviral applications.

PMID- 9915778
TI  - Effect of recombinant soluble P-selectin glycoprotein ligand-1 on leukocyte
      endothelium interaction in vivo. Role in rat traumatic shock.
AB  - -Traumatic shock induces profound pathophysiological alterations and initiates
      inflammatory reactions in many tissues, thus resulting in acute multiple organ
      damage (eg, intestine, pancreas, and liver). In the rat, Noble-Collip drum trauma
      increases P-selectin expression on the vascular endothelium as a result of loss
      of endothelium-derived NO. Here we postulated that blockade of the earliest steps
      in leukocyte adhesion (ie, leukocyte rolling) via administration of a recombinant
      soluble form of P-selectin glycoprotein ligand-1 (PSGL-1; the recombinant soluble
      form is rsPSGL.Ig) would attenuate selectin-mediated events observed in the rat
      during traumatic shock. Using intravital microscopy of the rat mesenteric
      microvasculature, we found that intravenous infusion of rsPSGL.Ig significantly
      inhibited leukocyte-endothelium interaction (ie, leukocyte rolling, adherence,
      and transmigration) induced by traumatic shock as well as by activation of the
      microvascular endothelium with 50 micromol/L NG-nitro-L-arginine methyl ester.
      Immunohistochemical detection of P-selectin on the mesenteric venular endothelial
      surface demonstrated that rsPSGL.Ig functionally neutralizes effects of P
      selectin on the endothelial cell surface rather than attenuating P-selectin
      expression. Systemic administration of rsPSGL.Ig to traumatized rats prolonged
      survival time and survival rate, significantly attenuating ileal myeloperoxidase
      activity and significantly preserving mesenteric endothelial function.
      Furthermore, PSGL-1 mRNA levels were significantly increased in the blood of
      traumatized rats and were reduced after systemic administration of rsPSGL.Ig.
      Thus, soluble recombinant forms of PSGL-1 are able to ameliorate acute shock
      states by suppressing selectin-mediated leukocyte-endothelium interaction at both
      the functional and molecular levels.

PMID- 9915779
TI  - Anoxia/reoxygenation-induced tolerance with respect to polymorphonuclear
      leukocyte adhesion to cultured endothelial cells. A nuclear factor-kappaB
      mediated phenomenon.
AB  - Exposing human umbilical vein endothelial cells (HUVECs) to anoxia/reoxygenation
      (A/R) results in an increase in polymorphonuclear leukocyte (PMN) adhesion to
      HUVECs. This A/R-induced hyperadhesion is completely prevented by a previous (24
      hours earlier) exposure of HUVECs to A/R. This phenomenon has been termed "A/R
      tolerance." Exposing HUVECs to A/R induces an increase in nuclear factor kappaB
      (NF-kappaB) in HUVEC nuclei within 4 hours. Interfering with either NF-kappaB
      activation (proteasome inhibitor) or translocation (double-stranded
      oligonucleotides containing NF-kappaB binding sequence) prevents the development
      of A/R tolerance (ie, the increase in A/R-induced PMN adhesion to HUVECs is the
      same after the first and second A/R challenges). NO production by HUVECs is
      increased after the second A/R challenge, but not after the first A/R challenge.
      Inhibition of NO synthase (NOS) during the second A/R challenge prevents the
      development of A/R tolerance with respect to PMN adhesion. However, while HUVECs
      contained endothelial NOS protein, no inducible NOS was detected in either
      tolerant or nontolerant cells. Further studies indicated that inhibition of GTP
      cyclohydrolase I (an enzyme involved in de novo synthesis of an important
      cofactor for NOS activity, tetrahydrobiopterin) prevented the generation of NO in
      A/R-tolerant cells. Extracellular generation of NO (NO donor) did not effect the
      hyperadhesion response induced by the initial A/R challenge. A/R also induced an
      oxidant stress in naive HUVECs, but not in A/R-tolerant HUVECs. Inhibition of NOS
      during the second A/R insult results in the generation of an oxidant stress
      similar to that observed after the first A/R challenge. Taken together, the
      findings of the present study are consistent with a role for NF-kappaB in the
      development of A/R tolerance (with respect to PMN adhesion), perhaps by
      transcriptional regulation of GTP-cyclohydrolase. The increased NO production
      during the second A/R insult reduces PMN adhesion most likely by reducing the
      intracellular oxidant stress induced by A/R.

PMID- 9915780
TI  - Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty
      injury. Influence of redox state and cell phenotype.
AB  - We have observed that acute medial cell loss is an initial event in the response
      to vascular injury induced by balloon-catheter distention of the rabbit carotid
      artery. Numerous apoptotic medial cells were observed as early as 30 minutes
      after balloon inflation, and a 70% loss of cellularity was evident by 90 minutes.
      Balloon injury was associated with oxidative stress as reflected by a fall in
      glutathione levels by 63% within 30 minutes after injury. We hypothesized that
      balloon injury activated a redox-sensitive signaling pathway coupled to the
      regulation of apoptosis. Indeed, the activity of the proapoptotic signal
      mediator, stress-activated protein kinase, was increased severalfold within 10
      minutes after injury. Moreover, modifying the vascular redox state by the
      administration of 1 of 2 structurally dissimilar antioxidants, N-acetyl cysteine
      or pyrrolidine dithiocarbamate, markedly attenuated both stress-activated protein
      kinase activation and the induction of apoptosis at 30 minutes. We hypothesized
      further that the induction of vascular smooth muscle cell apoptosis is modulated
      by phenotype. In contrast to medial cells, we observed that neointimal cells were
      relatively resistant to apoptotic death induced by angioplasty injury. This
      resistance to balloon injury-induced death was associated with an upregulation of
      the antiapoptotic mediator bcl-xL. This study suggests that acute apoptotic cell
      death after vascular injury is a highly regulated process governed by cellular
      redox state and the relative expression of antiapoptotic genes. Angioplasty
      induced vascular cell apoptosis may be an important determinant of vascular
      remodeling and restenosis.

PMID- 9915782
TI  - Correction 

PMID- 9915781
TI  - Troponin I, stunning, hypertrophy, and failure of the heart.

PMID- 9915783
TI  - Molecular basis of insulin-stimulated GLUT4 vesicle trafficking. Location!
      Location! Location!

PMID- 9915784
TI  - Association of the p75 neurotrophin receptor with TRAF6.
AB  - In addition to the Trk tyrosine kinase receptors, neurotrophins also bind to a
      second receptor, p75, a member of the tumor necrosis factor receptor superfamily.
      Several signaling pathways have been implicated for p75 in the absence of Trk
      receptors, including induction of NF-kappaB and c-Jun kinase activities and
      increased production of ceramide. However, to date, the mechanisms by which the
      p75 receptor initiates intracellular signal transduction have not been defined.
      Here we report a specific interaction between p75 and TRAF6 (tumor necrosis
      factor receptor-associated factor-6) after transient transfection in HEK293T
      cells. The interaction was ligand-dependent and maximal at 100 ng/ml of nerve
      growth factor (NGF). Other neurotrophins also promoted the association of TRAF6
      with p75 but to a lesser extent. The binding of TRAF6 was localized to the
      juxtamembrane region of p75 by co-immunoprecipitation and Western blotting. To
      assess the functional significance of this interaction, we have tested responses
      in cultured Schwann cells that express p75 and TRAF6. An NGF-mediated increase in
      the nuclear localization of the p65 subunit of NF-kappaB could be blocked by the
      introduction of a dominant negative form of TRAF6 in Schwann cells. These results
      indicate that TRAF6 can potentially function as a signal transducer for NGF
      actions through the p75 receptor.

PMID- 9915785
TI  - Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in
      the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'
      phosphosulfate synthase.
AB  - 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) synthase is a bifunctional protein
      consisting of an NH2-terminal APS kinase and a COOH-terminal ATP sulfurylase.
      Both catalytic activities require ATP; the APS kinase domain involves cleavage of
      the beta-gamma phosphodiester bond of ATP, whereas the ATP sulfurylase domain
      involves cleavage of the alpha-beta phosphodiester bond of ATP. Previous
      mutational studies have suggested that beta-gamma phosphodiesterase activity
      involves a highly conserved NTP-binding P-loop motif located in the adenosine-5'
      phosphosulfate kinase domain of PAPS synthases. Sequence alignment analysis of
      PAPS synthases and the superfamily of TagD-related nucleotidylyltransferases
      revealed the presence of a highly conserved HXGH motif in the ATP sulfurylase
      domain of PAPS synthases, a motif implicated in the alpha-beta phosphodiesterase
      activity of cytidylyltransferases. Thus, site-selected mutagenesis of the HXGH
      motif in the ATP sulfurylase domain of human PAPS synthase (amino acids 425-428)
      was performed to examine this possibility. Either H425A or H428A mutation
      produced an inactive enzyme. In contrast, a N426K mutation resulted in increased
      enzymatic activity. A G427A single mutant resulted in only a modest 30% reduction
      in catalytic activity, whereas a G427A/H428A double mutant produced an inactive
      enzyme. These results suggest an important role for the HXGH histidines in the
      ATP sulfurylase activity of bifunctional PAPS synthase and support the hypothesis
      that the highly conserved HXGH motif found in the ATP sulfurylase domain of PAPS
      synthases is involved in ATP binding and alpha-beta phosphodiesterase activity.

PMID- 9915786
TI  - CO ligation intermediates and the mechanism of hemoglobin cooperativity.
AB  - Direct experimental resolution of the ligation intermediates for the reaction of
      human hemoglobin with CO reveals the distribution of ligated states as a function
      of saturation. At low saturation, binding of CO occurs with slightly higher
      affinity to the beta chains, but pairwise interactions are more pronounced
      between the alpha chains. At high saturation, the two chains tend to behave
      identically. The sequence of CO ligation reconstructed from the distribution of
      intermediates shows that the overall increase in CO affinity is 588-fold, but it
      is not distributed uniformly among the ligation steps. The affinity increases
      16.5-fold in the second ligation step, 4.6-fold in the third ligation step, and
      7.7-fold in the fourth ligation step. This pattern and the detailed distribution
      of ligated states cannot be immediately reconciled with the predictions of either
      the concerted allosteric model of Monod-Wyman-Changeux or the sequential model of
      Koshland-Nemethy-Filmer and underscore a more subtle mechanism for hemoglobin
      cooperativity.

PMID- 9915787
TI  - A built-in arginine finger triggers the self-stimulatory GTPase-activating
      activity of rho family GTPases.
AB  - Signal transduction through the Rho family GTPases requires regulated cycling of
      the GTPases between the active GTP-bound state and the inactive GDP-bound state.
      Rho family members containing an arginine residue at position 186 in the C
      terminal polybasic region were found to possess a self-stimulatory GTPase
      activating protein (GAP) activity through homophilic interaction, resulting in
      significantly enhanced intrinsic GTPase activities. This arginine residue
      functions effectively as an "arginine finger" in the GTPase activating reaction
      to confer the catalytic GAP activity but is not essential for the homophilic
      binding interactions of Rho family proteins. The arginine 186-mediated negative
      regulation seems to be absent from Cdc42, a Rho family member important for cell
      division cycle regulation, of lower eukaryotes, yet appears to be a part of the
      turn-off machinery of Cdc42 from higher eukaryotes. Introduction of the arginine
      186 mutation into S. cerevisiae CDC42 led to phenotypes consistent with down
      regulated CDC42 function. Thus, specific Rho family GTPases may utilize a built
      in arginine finger, in addition to RhoGAPs, for negative regulation.

PMID- 9915788
TI  - Reverse transcription-polymerase chain reaction products of alternatively spliced
      mRNAs form DNA heteroduplexes and heteroduplex complexes.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) is frequently used to
      simultaneously detect mRNA isoforms, which are generated by alternative splicing.
      Here we characterize two previously unrecognized RT-PCR products of vascular
      endothelial growth factor (VEGF) RNA. DNA products with apparent sizes of 600 and
      1200 base pairs (bp) were detected at high cycle numbers. Heat denaturation of
      the smaller product and subsequent reannealing revealed that it was a
      heteroduplex consisting of two different DNA strands. These were identified by
      DNA sequencing as the amplification products of two VEGF transcripts, i.e.
      VEGF121 and VEGF165, which differ by the presence of one exon. S1 nuclease
      analysis showed that this exon is bulged out as a single-stranded loop. Purified
      heteroduplexes in solution were found to form a 1200-bp DNA product which could
      be reconverted into 600-bp DNA heteroduplexes by mild denaturation at 70
      degreesC. These findings suggest that this product is formed by base pairing of
      complementary heteroduplex loops and represents a novel four-stranded DNA
      structure.

PMID- 9915789
TI  - Evidence that endoplasmic reticulum (ER)-associated degradation of cystic
      fibrosis transmembrane conductance regulator is linked to retrograde
      translocation from the ER membrane.
AB  - The ubiquitin-proteasome pathway has been implicated in the degradation of newly
      synthesized, misfolded and unassembled proteins in the endoplasmic reticulum
      (ER). Using a cell-free reticulocyte lysate system we have examined the
      relationship between biosynthesis and ER-associated degradation of the cystic
      fibrosis transmembrane conductance regulator (CFTR), a polytopic protein with 12
      predicted transmembrane segments. Our results provide direct evidence that full
      length, glycosylated and membrane-integrated CFTR is a substrate for degradation
      and that degradation involves polyubiquitination and cytosolic proteolytic
      activity. CFTR ubiquitination was both temperature- and ATP-dependent.
      Degradation was significantly inhibited by EDTA, apyrase, and the proteasome
      inhibitors hemin and MG132. Degradation was inhibited to a lesser extent by
      clasto-lactacystin beta-lactone, ALLN, and Nalpha-tosyl-L-phenylalanine
      chloromethyl ketone and was relatively unaffected by lactacystin and N-tosyl
      lysyl chloromethyl ketone. In the presence of hemin, polyubiquitinated CFTR
      remained tightly associated with ER microsomes. However, membrane-bound
      ubiquitinated CFTR could be subsequently degraded into trichloroacetic acid
      soluble fragments upon incubation in hemin-free, ATP-containing lysate. Thus ER
      associated degradation of CFTR occurs via a membrane-bound, rather than
      cytosolic, intermediate and likely involves recruitment of degradation machinery
      to the ER membrane. Our data suggest a model in which the degradation of
      polytopic proteins such as CFTR is coupled to retrograde translocation and
      removal of the polypeptide from the lipid bilayer.

PMID- 9915790
TI  - Three classes of inhibitors share a common binding domain in mitochondrial
      complex I (NADH:ubiquinone oxidoreductase).
AB  - We have developed two independent methods to measure equilibrium binding of
      inhibitors to membrane-bound and partially purified NADH:ubiquinone
      oxidoreductase (complex I) to characterize the binding sites for the great
      variety of hydrophobic compounds acting on this large and complicated enzyme.
      Taking advantage of a partial quench of fluorescence upon binding of the
      fenazaquin-type inhibitor 2-decyl-4-quinazolinyl amine to complex I in bovine
      submitochondrial particles, we determined a Kd of 17 +/- 3 nM and one binding
      site per complex I. Equilibrium binding studies with [3H]dihydrorotenone and the
      aminopyrimidine [3H]AE F119209 (4(cis-4-[3H]isopropyl cyclohexylamino)-5-chloro-6
      ethyl pyrimidine) using partially purified complex I from Musca domestica
      exhibited little unspecific binding and allowed reliable determination of
      dissociation constants. Competition experiments consistently demonstrated that
      all tested hydrophobic inhibitors of complex I share a common binding domain with
      partially overlapping sites. Although the rotenone site overlaps with both the
      piericidin A and the capsaicin site, the latter two sites do not overlap. This is
      in contrast to the interpretation of enzyme kinetics that have previously been
      used to define three classes of complex I inhibitors. The existence of only one
      large inhibitor binding pocket in the hydrophobic part of complex I is discussed
      in the light of possible mechanisms of proton translocation.

PMID- 9915791
TI  - CPG16, a novel protein serine/threonine kinase downstream of cAMP-dependent
      protein kinase.
AB  - Gene expression is necessary for the formation and consolidation of long term
      memory in both invertebrates and vertebrates. Here, we describe the expression
      and characterization of candidate plasticity gene 16 (cpg16), a protein
      serine/threonine kinase that was previously isolated from rat hippocampus as a
      plasticity-related gene. CPG16, when expressed in and purified from bacteria and
      COS7 cells, was only capable of autophosphorylation and phosphorylation of myelin
      basic protein but failed to phosphorylate many other peptides and proteins in in
      vitro phosphorylation assays. Recombinant CPG16, when overexpressed and purified
      from COS7 cells, had a relatively low level of autophosphorylation activity. This
      activity was significantly stimulated when cAMP-elevating agents (forskolin, 8
      bromo-cAMP) were added to the cells but not by any other extracellular stimuli
      tested, e.g. serum, phorbol esters, and a calcium ionophore. Although the
      stimulation of CPG16 activity was inhibited by the cAMP-dependent protein kinase
      inhibitor H-89, it did not serve as a direct substrate for this kinase. This
      suggests that CPG16 may be activated by a cAMP-stimulated protein kinase cascade.
      Immunolocalization studies in COS7 and NIH-3T3 cells showed mostly cytoplasmic
      localization of CPG16 that turned partially nuclear upon stimulation with 8-bromo
      cAMP. Moreover, overexpression of CPG16 seems to partially inhibit cAMP
      stimulated activity of the transcription factor CREB (cAMP response element
      binding protein), suggesting its involvement in the down-regulation of cAMP
      induced transcription. Thus, CPG16 is a protein serine/threonine kinase that may
      be involved in a novel signaling pathway downstream of cAMP-dependent protein
      kinase.

PMID- 9915792
TI  - Transient ADP-ribosylation of a 2'-phosphate implicated in its removal from
      ligated tRNA during splicing in yeast.
AB  - The last step of tRNA splicing in yeast is catalyzed by Tpt1 protein, which
      transfers the 2'-phosphate from ligated tRNA to NAD to produce ADP-ribose 1"-2"
      cyclic phosphate (Appr>p). Structural and functional TPT1 homologs are found
      widely in eukaryotes and, surprisingly, also in Escherichia coli, which does not
      have this class of tRNA splicing. To understand the possible roles of the Tpt1
      enzymes as well as the unusual use of NAD, the reaction mechanism of the E. coli
      homolog KptA was investigated. We show here that KptA protein removes the 2'
      phosphate from RNA via an intermediate in which the phosphate is ADP-ribosylated
      followed by a presumed transesterification to release the RNA and generate
      Appr>p. The intermediate was characterized by analysis of its components and
      their linkages, using various labeled substrates and cofactors. Because the yeast
      and mouse Tpt1 proteins, like KptA protein, can catalyze the conversion of the
      KptA-generated intermediate to both product and the original substrate, these
      enzymes likely use the same reaction mechanism. Step 1 of this reaction is
      strikingly similar to the ADP-ribosylation of proteins catalyzed by a number of
      bacterial toxins.

PMID- 9915793
TI  - Phosphorylation of the thromboxane receptor alpha, the predominant isoform
      expressed in human platelets.
AB  - A single gene encodes the human thromboxane receptor (TP), of which there are two
      identified splice variants, alpha and beta. Both isoforms are rapidly
      phosphorylated in response to thromboxane agonists when overexpressed in human
      embryonic kidney 293 cells; this phenomenon is only slightly altered by
      inhibitors of protein kinase C. Pharmacological studies have defined two classes
      of TP in human platelets; sites that bind the agonist I-BOP with high affinity
      support platelet shape change. Low affinity sites, which irreversibly bind the
      antagonist GR 32191, transduce platelet activation and aggregation. Isoform
      specific antibodies permitted detection of TPalpha, but not TPbeta, from human
      platelets, although mRNA for both isoforms is present. A broad protein band of 50
      60 kDa, reflecting the glycosylated receptor, was phosphorylated upon activation
      of platelets for 2 min with I-BOP. This was a rapid ( approximately 30 s) and
      transient (maximum, 2-4 min) event and was inhibited by TP antagonists. Both
      arachidonic acid and low concentrations of collagen stimulated TPalpha
      phosphorylation, which was blocked by cyclooxygenase inhibition or TP antagonism.
      Blockade of the low affinity TP sites with GR 32191 prevented I-BOP-induced
      TPalpha phosphorylation. This coincided with agonist-induced platelet aggregation
      and activation but not shape change. Also, activation of these sites with the
      isoprostane iPF2alpha-III induced platelet shape change but not TPalpha
      phosphorylation. Heterologous TP phosphorylation was observed in aspirin-treated
      platelets exposed to thrombin, high concentrations of collagen, and the calcium
      ionophore A 23187. Both homologous and heterologous agonist-induced
      phosphorylation of endogenous TPalpha was blocked by protein kinase C inhibitors.
      TPalpha was the only isoform detectably translated in human platelets. This
      appeared to correspond to the activation of the low affinity site defined by the
      antagonist GR 32191 and not activated by the high affinity agonist, iPF2alpha
      III. Protein kinase C played a more important role in agonist-induced
      phosphorylation of native TPalpha in human platelets than in human embryonic
      kidney 293 cells overexpressing recombinant TPalpha.

PMID- 9915794
TI  - Stability and DNA binding of the phd protein of the phage P1 plasmid addiction
      system.
AB  - The plasmid addiction module of bacteriophage P1 encodes two proteins, Doc, a
      toxin that is stable to proteolytic degradation, and Phd, the toxin's antidote
      that is proteolytically unstable. Phd has been shown to autoregulate its
      expression by specific DNA binding. Here, we investigate the secondary structure
      and thermal stability of Phd, the effect of operator DNA binding on the structure
      and stability of Phd, and the stoichiometry, affinity, and cooperativity of Phd
      binding to operator subsites and intact operator DNA. Phd folds as a monomer at
      low temperatures or in the presence of osmolytes but exists predominantly in an
      unfolded conformation at 37 degreesC. The native state of Phd is stabilized by
      operator binding. Two Phd monomers bind to each operator subsite, and four
      monomers bind to the intact operator. The subsite binding reaction shows a second
      order dependence on protein concentration and monomer-bound DNA species are
      unpopulated, suggesting that two Phd molecules bind cooperatively to each
      operator subsite. In intact operator binding experiments, both dimer-bound and
      tetramer-bound DNA species are populated, and binding occurs at protein
      concentrations similar to those required for subsite binding, suggesting that
      there is no significant dimer-dimer cooperativity.

PMID- 9915795
TI  - GATA-6 activates transcription of thyroid transcription factor-1.
AB  - Thyroid transcription factor-1 (TTF-1) is expressed in respiratory epithelial
      cells, where it regulates the transcription of target genes expressed in a cell
      selective manner. GATA-5 and -6, members of the zinc finger family of
      transcription factors, are also expressed in various cell types within in the
      developing lung. In the present work, GATA-6 mRNA was detected in adult mouse
      lung, purified mouse type II epithelial cells, and differentiated mouse pulmonary
      adenocarcinoma cells (MLE-15 cells), being co-expressed with TTF-1 mRNA. In order
      to test whether GATA factors regulated TTF-1 gene transcription, GATA-5 and -6
      expression vectors were co-transfected with TTF-1 luciferase expression vector.
      GATA-6, but not GATA-5, markedly activated TTF-1 gene transcription in HeLa
      cells. EMSA and supershift analysis with GATA-6 antiserum demonstrated that GATA
      6 in MLE-15 cell nuclear extracts bound to an element located 96-101 base pairs
      from major start of TTF-1 gene transcription. Site directed mutagenesis of the
      GATA element in the TTF-1 promoter region inhibited transactivation by GATA-6 in
      HeLa cells. GATA-6 is co-expressed with TTF-1 in the respiratory epithelium in
      vivo and respiratory epithelial cells in vitro. GATA-6 strongly enhanced activity
      of the human TTF-1 gene promoter in vitro. These findings support the concept
      that GATA-6 may play an important role in lung cell differentiation and gene
      expression, at least in part by altering the expression of TTF-1 and its
      potential targets.

PMID- 9915796
TI  - OC-2, a novel mammalian member of the ONECUT class of homeodomain transcription
      factors whose function in liver partially overlaps with that of hepatocyte
      nuclear factor-6.
AB  - Transcription factors of the ONECUT class, whose prototype is hepatocyte nuclear
      factor (HNF)-6, are characterized by the presence of a single cut domain and by a
      peculiar homeodomain (Lannoy, V. J., Burglin, T. R., Rousseau, G. G., and
      Lemaigre, F. P. (1998) J. Biol. Chem. 273, 13552-13562). We report here the
      identification and characterization of human OC-2, the second mammalian member of
      this class. The OC-2 gene is located on human chromosome 18. The distribution of
      OC-2 mRNA in humans is tissue-restricted, the strongest expression being detected
      in the liver and skin. The amino acid sequence of OC-2 contains several regions
      of high similarity to HNF-6. The recognition properties of OC-2 for binding sites
      present in regulatory regions of liver-expressed genes differ from, but overlap
      with, those of HNF-6. Like HNF-6, OC-2 stimulates transcription of the hnf-3beta
      gene in transient transfection experiments, suggesting that OC-2 participates in
      the network of transcription factors required for liver differentiation and
      metabolism.

PMID- 9915797
TI  - Cross-talk between janus kinase-signal transducer and activator of transcription
      (JAK-STAT) and peroxisome proliferator-activated receptor-alpha (PPARalpha)
      signaling pathways. Growth hormone inhibition of pparalpha transcriptional
      activity mediated by stat5b.
AB  - Hepatic peroxisome proliferation induced by structurally diverse non-genotoxic
      carcinogens is mediated by the nuclear receptor peroxisome proliferator-activated
      receptor (PPARalpha) and can be inhibited by growth hormone (GH). GH-stimulated
      Janus kinase-signal transducer and activator of transcription 5b (JAK2/STAT5b)
      signaling and the PPAR activation pathway were reconstituted in COS-1 cells to
      investigate the mechanism for this GH inhibitory effect. Activation of STAT5b
      signaling by either GH or prolactin inhibited, by up to 80-85%, ligand-induced,
      PPARalpha-dependent reporter gene transcription. GH failed to inhibit 15-deoxy
      Delta12, 14-prostaglandin-J2-stimulated gene transcription mediated by an
      endogenous COS-1 PPAR-related receptor. GH inhibition of PPARalpha activity
      required GH receptor and STAT5b and was not observed using GH-activated STAT1 in
      place of STAT5b. GH inhibition was not blocked by the mitogen-activated protein
      kinase pathway inhibitor PD98059. STAT5b-PPARalpha protein-protein interactions
      could not be detected by anti-STAT5b supershift analysis of PPARalpha-DNA
      complexes. The GH inhibitory effect required the tyrosine phosphorylation site
      (Tyr-699) of STAT5b, an intact STAT5b DNA binding domain, and the presence of a
      COOH-terminal trans-activation domain. Moreover, GH inhibition was reversed by a
      COOH-terminal-truncated, dominant-negative STAT5b mutant. STAT5b must thus be
      nuclear and transcriptionally active to mediate GH inhibition of PPARalpha
      activity, suggesting an indirect inhibition mechanism, such as competition for an
      essential PPARalpha coactivator or STAT5b-dependent synthesis of a more proximal
      PPARalpha inhibitor. The cross-talk between STAT5b and PPARalpha signaling
      pathways established by these findings provides new insight into the mechanisms
      of hormonal and cytokine regulation of hepatic peroxisome proliferation.

PMID- 9915798
TI  - The common tetratricopeptide repeat acceptor site for steroid receptor-associated
      immunophilins and hop is located in the dimerization domain of Hsp90.
AB  - Structurally related tetratricopeptide repeat motifs in steroid receptor
      associated immunophilins and the STI1 homolog, Hop, mediate the interaction with
      a common cellular target, hsp90. We have identified the binding domain in hsp90
      for cyclophilin 40 (CyP40) using a two-hybrid system screen of a mouse cDNA
      library. All isolated clones encoded the intact carboxyl terminus of hsp90 and
      overlapped with a common region corresponding to amino acids 558-724 of murine
      hsp84. The interaction was confirmed in vitro with bacterially expressed CyP40
      and deletion mutants of hsp90beta and was delineated further to a 124-residue
      COOH-terminal segment of hsp90. Deletion of the conserved MEEVD sequence at the
      extreme carboxyl terminus of hsp90 precludes interaction with CyP40, signifying
      an important role for this motif in hsp90 function. We show that CyP40 and Hop
      display similar interaction profiles with hsp90 truncation mutants and present
      evidence for the direct competition of Hop and FK506-binding protein 52 with
      CyP40 for binding to the hsp90 COOH-terminal region. Our results are consistent
      with a common tetratricopeptide repeat interaction site for Hop and steroid
      receptor-associated immunophilins within a discrete COOH-terminal domain of
      hsp90. This region of hsp90 mediates ATP-independent chaperone activity, overlaps
      the hsp90 dimerization domain, and includes structural elements important for
      steroid receptor interaction.

PMID- 9915799
TI  - Molecular cloning and expression of a third member of the heparan sulfate/heparin
      GlcNAc N-deacetylase/ N-sulfotransferase family.
AB  - N-Deacetylation and N-sulfation of N-acetylglucosamine residues in heparan
      sulfate and heparin initiate a series of chemical modifications that ultimately
      lead to oligosaccharide sequences with specific ligand binding properties. These
      reactions are catalyzed by GlcNAc N-deacetylase/N-sulfotransferase (NDST), a
      monomeric enzyme with two catalytic activities. Two genes encoding NDST isozymes
      have been described, one from rat liver (NDST1) and another from murine
      mastocytoma (NDST2). Both isozymes are expressed in tissues in varying amounts,
      but their relative contribution to heparan sulfate formation in any one tissue is
      unknown. We now report the identification of a third member of the NDST family,
      designated NDST3. A full-length cDNA clone (3.2 kilobase pairs) encoding a 873
      amino acid protein was obtained from a human fetal/infant brain cDNA library.
      Human NDST3 (hNDST3) has a nucleotide sequence homologous but not identical to
      hNDST1 and NDST2. The deduced amino acid sequence shows 70% and 65% amino acid
      identity to that of hNDST1 and NDST2, respectively. A soluble chimera of hNDST3
      and protein A exhibited both N-deacetylase and N-sulfotransferase activity,
      confirming its enzymatic identity. Northern blot analysis of human fetal brain
      poly(A)+ RNA showed a single transcript of 6.4 kilobase pairs. Reverse
      transcription polymerase chain reaction analysis revealed more restricted tissue
      expression of hNDST3 than hNDST1 and NDST2, and high levels in brain, liver, and
      kidney. Analysis of Chinese hamster ovary cells revealed expression of NDST1 and
      NDST2, but not NDST3. In a Chinese hamster ovary cell mutant exhibiting reduced N
      sulfotransferase activity and reduced sulfation of heparan sulfate (Bame, K. J.,
      and Esko, J. D. (1989) J. Biol. Chem. 264, 8059-8065), expression of NDST1 was
      greatly reduced, but NDST2 was expressed normally, suggesting that both enzymes
      are involved in heparan sulfate assembly. The discovery of multiple NDST isozymes
      suggests that the assembly of heparan sulfate is much complicated than previously
      appreciated.

PMID- 9915800
TI  - Human papillomavirus DNA replication. Interactions between the viral E1 protein
      and two subunits of human dna polymerase alpha/primase.
AB  - Papovaviruses are valuable models for the study of DNA replication in higher
      eukaryotic organisms, as they depend on host factors for replication of their
      DNA. In this study we investigate the interactions between the human
      papillomavirus type 11 (HPV-11) origin recognition and initiator protein E1 and
      human polymerase alpha/primase (pol alpha/primase) subunits. By using a variety
      of physical assays, we show that both 180- (p180) and 70-kDa (p70) subunits of
      pol alpha/primase interact with HPV-11 E1. The interactions of E1 with p180 and
      p70 are functionally different in cell-free replication of an HPV-11 origin
      containing plasmid. Exogenously added p180 inhibits both E2-dependent and E2
      independent cell-free replication of HPV-11, whereas p70 inhibits E2-dependent
      but stimulates E2-independent replication. Our experiments indicate that p70 does
      not physically interact with E2 and suggest that it may compete with E2 for
      binding to E1. A model of how E2 and p70 sequentially interact with E1 during
      initiation of viral DNA replication is proposed.

PMID- 9915801
TI  - Poliovirus RNA-dependent RNA polymerase (3Dpol) is sufficient for template
      switching in vitro.
AB  - We have performed a systematic, quantitative analysis of the kinetics of
      nucleotide incorporation catalyzed by poliovirus RNA-dependent RNA polymerase,
      3Dpol. Homopolymeric primer/templates of defined length were used to evaluate the
      contribution of primer and template length and sequence to the efficiency of
      nucleotide incorporation without the complication of RNA structure.
      Interestingly, thermodynamic stability of the duplex region of these
      primer/templates was more important for efficient nucleotide incorporation than
      either primer or template length. Surprisingly, products greater than unit length
      formed in all reactions regardless of length or sequence. Neither a distributive
      nor a processive slippage mechanism could be used to explain completely the
      formation of long products. Rather, the data were consistent with a template
      switching mechanism. All of the nucleotide could be polymerized during the course
      of the reaction. However, very few primers could be extended, suggesting an
      inverse correlation between the efficiency of primer utilization and that of
      nucleotide incorporation. Therefore, the greatest fraction of incorporated
      nucleotide derives from a small fraction of enzyme when radioactive nucleotide
      and homopolymeric primer/template substrates are employed. The impact of these
      results on mechanistic studies of 3Dpol-catalyzed nucleotide incorporation and
      RNA recombination are discussed.

PMID- 9915802
TI  - Localization of phospholipase D in detergent-insoluble, caveolin-rich membrane
      domains. Modulation by caveolin-1 expression and caveolin-182-101.
AB  - The activation of cellular phospholipase D (PLD) is implicated in vesicular
      trafficking and signal transduction. Two mammalian PLD forms, designated PLD1 and
      PLD2, have been cloned, but their cellular localization and function are not
      fully understood. Here, we report that in HaCaT human keratinocytes, as well as
      other cell lines, PLD activity is highly enriched in low density, Triton X-100
      insoluble membrane domains that contain the caveolar marker protein caveolin-1.
      Similar to other PLDs, the PLD activity in these membrane domains is stimulated
      by phosphatidylinositol 4, 5-bisphosphate and is inhibited by neomycin.
      Immunoblot analysis indicated that caveolin-rich membrane domains do not contain
      the PLD1 isoform. Stable transfection of mouse PLD2 in Chinese hamster ovary
      cells greatly increased PLD activity in these domains compared with PLD activity
      in control Chinese hamster ovary cells transfected with vector alone. PLD
      activity is enriched in low density Triton-insoluble membrane domains also in
      U937 promonocytes, even though these cells do not express caveolin-1. In U937
      cells, also, PLD1 is largely excluded from low density Triton-insoluble membrane
      domains. Expression of recombinant caveolin-1 in v-Src-transformed NIH-3T3 cells
      resulted in up-regulation of PLD activity in the caveolin-containing membrane
      domains. The caveolin scaffolding peptide (caveolin-182-101) modulated the
      caveolar PLD activity, causing stimulation at concentration of 1-10 microM and
      inhibition at concentrations >10 microM. We conclude that a PLD activity, which
      is likely to represent PLD2, is enriched in low density Triton-insoluble membrane
      domains. The effects of caveolin-1 expression and of the caveolin scaffolding
      peptide suggest that in cells that express caveolin-1, PLD may be targeted to
      caveolae. The possible functions of PLD in the dynamics of caveolae and related
      domains and in signal transduction processes are discussed.

PMID- 9915803
TI  - Editing of cytochrome b mRNA in physarum mitochondria.
AB  - The reading frame in the mRNA for the cytochrome b apoprotein in mitochondria of
      Physarum polycephalum is created by the insertion of 43 nucleotides in the mRNA
      relative to the mtDNA sequence encoding it (RNA editing). Most of these
      insertions (31) are single cytidines; however, single uridines are inserted at
      six sites, and the dinucleotides, CU and GC, are inserted at two sites and one
      site, respectively. These insertions create a 392-codon reading frame in the
      mature mRNA. The amino acid sequence inferred from this reading frame has
      similarity to cytochrome b apoproteins encoded by other mtDNAs. The insertions
      are quite evenly distributed throughout the length of the reading frame with an
      average spacing of 27 nucleotides. This mRNA has the highest percentage (23%) of
      noncytidine insertions of any Physarum RNA characterized to date. cDNAs
      corresponding to partially edited RNAs can be enriched by selective
      amplification. Some cDNAs that lack the GC dinucleotide insertion are fully
      edited at sites flanking the GC dinucleotide insertion site. Similarly some cDNAs
      lack the CT dinucleotide insertion or have a CC or TT insertion flanked by a
      fully edited sequence. These results imply that dinucleotide editing occurs by a
      process separate from the global insertion of cytidines.

PMID- 9915804
TI  - Mitogen-activated protein kinase kinase 2 activation is essential for progression
      through the G2/M checkpoint arrest in cells exposed to ionizing radiation.
AB  - An increasing body of evidence suggests that mitogen-induced activation of the
      RAF/ERK signaling pathway is functionally separate from the stress-induced
      activation of the SEK/JNK/p38 signaling pathway. In general, stress stimuli
      strongly activate the p38s and the JNKs while only weakly activating ERK1 and
      ERK2. However, a number of independent groups have now shown that the RAF/ERK
      signaling pathway is strongly activated by ionizing radiation. In this work, we
      examine this paradox. We show that both mitogen-activated protein (MAP) kinase
      kinase 1 (MEK1) and MAP kinase kinase 2 (MEK2) are activated by ionizing
      radiation. Blockage of this activation through the use of dominant negative MEK2
      increases sensitivity of the cell to ionizing radiation and decreases the ability
      of a cell to recover from the G2/M cell cycle checkpoint arrest. Blocking MEK2
      activation does not affect double-strand DNA break repair, however. Although MEK1
      is activated to a lesser extent by ionizing radiation, expression of a dominant
      negative MEK1 does not affect radiation sensitivity of the cell, the G2/M
      checkpoint of the cell, or double-strand break repair. Because ionizing radiation
      leads to a different cell cycle arrest (G2/M arrest) than that typically seen
      with other stress stimuli, and because we have shown that MEK2 can affect G2/M
      checkpoint kinetics, these results provide an explanation for the observation
      that the MEKs can be strongly activated by ionizing radiation and only weakly
      activated by other stressful stimuli.

PMID- 9915805
TI  - Mutational analysis of cysteine-rich domains of the epithelium sodium channel
      (ENaC). Identification of cysteines essential for channel expression at the cell
      surface.
AB  - One of the characteristic features of the structure of the epithelial sodium
      channel family (ENaC) is the presence of two highly conserved cysteine-rich
      domains (CRD1 and CRD2) in the large extracellular loops of the proteins. We have
      studied the role of CRDs in the functional expression of rat alphabetagamma ENaC
      subunits by systematically mutating cysteine residues (singly or in combinations)
      into either serine or alanine. In the Xenopus oocyte expression system, mutations
      of two cysteines in CRD1 of alpha, beta, or gamma ENaC subunits led to a
      temperature-dependent inactivation of the channel. In CRD1, one of the cysteines
      of the rat alphaENaC subunit (Cys158) is homologous to Cys133 of the
      corresponding human subunit causing, when mutated to tyrosine (C133Y),
      pseudohypoaldosteronism type 1, a severe salt-loosing syndrome in neonates. In
      CRD2, mutation of two cysteines in alpha and beta but not in the gamma subunit
      also produced a temperature-dependent inactivation of the channel. The main
      features of the mutant cysteine channels are: (i) a decrease in cell surface
      expression of channel molecules that parallels the decrease in channel activity
      and (ii) a normal assembly or rate of degradation as assessed by nondenaturing co
      immunoprecipitation of [35S]methionine-labeled channel protein. These data
      indicate that the two cysteines in CRD1 and CRD2 are not a prerequisite for
      subunit assembly and/or intrinsic channel activity. We propose that they play an
      essential role in the efficient transport of assembled channels to the plasma
      membrane.

PMID- 9915806
TI  - Enhanced glutathione levels and oxidoresistance mediated by increased glucose-6
      phosphate dehydrogenase expression.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose
      phosphate pathway that is responsible for the generation of NADPH, which is
      required in many detoxifying reactions. We have recently demonstrated that G6PD
      expression is induced by a variety of chemical agents acting at different steps
      in the biochemical pathway controlling the intracellular redox status. Although
      we obtained evidence that the oxidative stress-mediated enhancement of G6PD
      expression is a general phenomenon, the functional significance of such G6PD
      induction after oxidant insult is still poorly understood. In this report, we
      used a GSH-depleting drug that determines a marked decrease in the intracellular
      pool of reduced glutathione and a gradual but notable increase in G6PD
      expression. Both effects are seen soon after drug addition. Once G6PD activity
      has reached the maximum, the GSH pool is restored. We suggest and also provide
      the first direct evidence that G6PD induction serves to maintain and regenerate
      the intracellular GSH pool. We used HeLa cell clones stably transfected with the
      human G6PD gene that display higher G6PD activity than the parent HeLa cells.
      Although the activities of glutathione peroxidase, glutathione reductase, and
      catalase were comparable in all strains, the concentrations of GSH were
      significantly higher in G6PD-overexpressing clones. A direct consequence of GSH
      increase in these cells is a decreased reactive oxygen species production, which
      makes these cells less sensitive to the oxidative burst produced by external
      stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong
      protection against oxidants-mediated cell killing. We also observe that NF-kappaB
      activation, in response to tumor necrosis factor-alpha treatment, is strongly
      reduced in human HeLa cells overexpressing G6PD.

PMID- 9915807
TI  - Hemoglobin endocytosis in Leishmania is mediated through a 46-kDa protein located
      in the flagellar pocket.
AB  - Four lines of evidence indicate that a specific high affinity binding site on the
      surface of Leishmania donovani promastigotes mediates rapid internalization and
      degradation of hemoglobin. 1) Binding and uptake of 125I-hemoglobin by Leishmania
      followed saturation kinetics and were competed by unlabeled hemoglobin but not by
      globin or hemin or other heme- or iron-containing proteins. 2) Immunogold
      labeling studies revealed that, at 4 degreesC, hemoglobin binding was localized
      in the flagellar pocket of the promastigotes. Indirect immunofluorescence assays
      showed that, at 37 degreesC, the bound hemoglobin in such cells entered an
      endocytic compartment within 2 min and dispersed throughout the cell body by 15
      min. 3) After incubation with hemoglobin-gold conjugates at 25 degreesC or 37
      degreesC, the particles accumulated in discrete intracellular vesicles. 4) A
      single biotinylated protein of 46 kDa was revealed when solubilized membranes
      from surface biotinylated intact Leishmania adsorbed by hemoglobin-agarose beads
      were subjected to SDS-polyacrylamide gel electrophoresis and Western blotting
      with avidin-horseradish peroxidase. Considered together, these data indicate that
      this 46-kDa protein on the cell surface of L. donovani promastigotes mediates the
      binding of hemoglobin and its rapid internalization through a vesicular pathway
      characteristic of receptor-mediated endocytosis.

PMID- 9915808
TI  - Phytanic acid activates the peroxisome proliferator-activated receptor alpha
      (PPARalpha) in sterol carrier protein 2-/ sterol carrier protein x-deficient
      mice.
AB  - We showed recently that a targeted null mutation in the murine sterol carrier
      protein 2-/sterol carrier protein x-gene (Scp2) leads to defective peroxisomal
      catabolism of 3,7,11, 15-tetramethylhexadecanoic acid (phytanic acid), peroxisome
      proliferation, hypolipidemia, and enhanced hepatic expression of several genes
      that have been demonstrated to be transcriptionally regulated by the peroxisome
      proliferator-activated receptor alpha (PPARalpha). As a broad range of fatty
      acids activates PPARalpha in vitro, we examined whether the latter effects could
      be because of phytanic acid-induced activation of this transcription factor.
      Dietary phytol supplementation was used to modulate the concentration of phytanic
      acid in C57Bl/6 and Scp2 (-/-) mice. We found that the serum concentrations of
      phytanic acid correlated well with the expression of genes encoding peroxisomal
      beta-oxidation enzymes and liver fatty acid-binding protein, which have all been
      demonstrated to contain functionally active peroxisome proliferator response
      elements in their promoter regions. In accordance with these findings, a
      stimulating effect on acyl-CoA oxidase gene expression was also observed after
      incubation of the rat hepatoma cell line MH1C1 with phytanic acid. Moreover,
      reporter gene studies revealed that phytanic acid induces the expression of a
      peroxisome proliferator response element-driven chloramphenicol transferase
      reporter gene comparable with strong peroxisome proliferators. In addition, the
      ability of phytanic acid to act as an inductor of PPARalpha-dependent gene
      expression corresponded with high affinity binding of this dietary branched chain
      fatty acid to recombinant PPARalpha. We conclude that phytanic acid can be
      considered as a bona fide physiological ligand of murine PPARalpha.

PMID- 9915809
TI  - Stoichiometry and kinetics of the high-affinity H+-coupled peptide transporter
      PepT2.
AB  - Proton-coupled peptide transporters mediate the absorption of a large variety of
      di- and tripeptides as well as peptide-like pharmacologically active compounds.
      We report a kinetic analysis of the rat kidney high-affinity peptide transporter
      PepT2 expressed in Xenopus oocytes. By use of simultaneous radioactive uptake and
      current measurements under voltage-clamp condition, the charge to substrate
      uptake ratio was found to be close to 2 for both D-Phe-L-Ala and D-Phe-L-Glu,
      indicating that the H+:substrate stoichiometry is 2:1 and 3:1 for neutral and
      anionic dipeptides, respectively. The higher stoichiometry for anionic peptides
      suggests that they are transported in the protonated form. For D-Phe-L-Lys, the
      charge:uptake ratio averaged 2.4 from pooled experiments, suggesting that Phe-Lys
      crosses the membrane via PepT2 either in its deprotonated (neutral) or its
      positively charged form, averaging a H+:Phe-Lys stoichiometry of 1.4:1. These
      findings led to the overall conclusion that PepT2 couples transport of one
      peptide molecule to two H+. This is in contrast to the low-affinity transporter
      PepT1 that couples transport of one peptide to one H+. Quinapril inhibited PepT2
      mediated currents in presence or in absence of external substrates. Oocytes
      expressing PepT2 exhibited quinapril-sensitive outward currents. In the absence
      of external substrate, a quinapril-sensitive proton inward current (proton leak)
      was also observed which, together with the observed pH-dependent PepT2-specific
      presteady-state currents (Ipss), indicates that at least one H+ binds to the
      transporter prior to substrate. PepT2 exhibited Ipss in response to
      hyperpolarization at pH 6.5-8.0. However, contrary to previous observations on
      various transporters, 1) no significant currents were observed corresponding to
      voltage jumps returning from hyperpolarization, and 2) at reduced extracellular
      pH, no significant Ipss were observed in either direction. Together with observed
      lower substrate affinities and decreased PepT2-mediated currents at
      hyperpolarized Vm, our data are consistent with the concept that
      hyperpolarization exerts inactivation effects on the transporter which are
      enhanced by low pH. Our studies revealed distinct properties of PepT2, compared
      with PepT1 and other ion-coupled transporters.

PMID- 9915810
TI  - Intermolecular and interdomain interactions of a dynamin-related GTP-binding
      protein, Dnm1p/Vps1p-like protein.
AB  - Dnm1p/Vps1p-like protein (DVLP) is a mammalian member of the dynamin GTPase
      family, which is classified into subfamilies on the basis of the structural
      similarity. Mammalian dynamins constitute the dynamin subfamily. DVLP belongs to
      the Vps1 subfamily, which also includes yeast Vps1p and Dnm1p. Typical structural
      features that discriminate between members of the Vps1 and dynamin subfamilies
      are that the former lacks the pleckstrin homology and Pro-rich domains. Dynamin
      exists as tetramers under physiological salt conditions, whereas under low salt
      conditions, it can polymerize into spirals that resemble the collar structures
      seen at the necks of constricted coated pits. In this study, we found that DVLP
      is also oligomeric, probably tetrameric, under physiological salt conditions and
      forms sedimentable large aggregates under low salt conditions. The data indicate
      that neither the pleckstrin homology nor Pro-rich domain is required for the self
      assembly. Analyses using the two-hybrid system and co-immunoprecipitation show
      that the N-terminal region containing the GTPase domain and a domain (DVH1)
      conserved across members of the dynamin and Vps1 subfamilies, can interact with
      the C-terminal region containing another conserved domain (DVH2). The data on the
      interdomain interaction of DVLP is compatible with the previous reports on the
      interdomain interaction of dynamin. Thus, the self-assembly mechanism of DVLP
      appears to resemble that of dynamin, suggesting that DVLP may also be involved in
      the formation of transport vesicles.

PMID- 9915811
TI  - Action of phosphatidylinositol-specific phospholipase Cgamma1 on soluble and
      micellar substrates. Separating effects on catalysis from modulation of the
      surface.
AB  - The kinetics of PI-PLCgamma1 toward a water-soluble substrate (inositol 1,2
      cyclic phosphate, cIP) and phosphatidylinositol (PI) in detergent mixed micelles
      were monitored by 31P NMR spectroscopy. That cIP is also a substrate (Km =
      approximately 15 mM) implies a two-step mechanism (intramolecular
      phosphotransferase reaction to form cIP followed by cyclic phosphodiesterase
      activity to form inositol-1-phosphate (I-1-P)). PI is cleaved by PI-PLCgamma1 to
      form cIP and I-1-P with the enzyme specific activity and ratio of products (cIP/I
      1-P) regulated by assay temperature, pH, Ca2+, and other amphiphilic additives.
      Cleavage of both cIP and PI by the enzyme is optimal at pH 5. The effect of Ca2+
      on PI-PLCgamma1 activity is unique compared with other isozymes enzymes: Ca2+ is
      necessary for the activity and low Ca2+ activates the enzyme; however, high Ca2+
      inhibits PI-PLCgamma1 hydrolysis of phosphoinositides (but not cIP) with the
      extent of inhibition dependent on pH, substrate identity (cIP or PI), substrate
      presentation (e.g. detergent matrix), and substrate surface concentration. This
      inhibition of PI-PLCgamma1 by high Ca2+ is proposed to derive from the divalent
      metal ion-inducing clustering of the PI and reducing its accessibility to the
      enzyme. Amphiphilic additives such as phosphatidic acid, fatty acid, and sodium
      dodecylsulfate enhance PI cleavage in micelles at pH 7.5 but not at pH 5.0; they
      have no effect on cIP hydrolysis at either pH value. These different kinetic
      patterns are used to propose a model for regulation of the enzyme. A key
      hypothesis is that there is a pH-dependent conformational change in the enzyme
      that controls accessibility of the active site to both water-soluble cIP and
      interfacially organized PI. The low activity enzyme at pH 7.5 can be activated by
      PA (or phosphorylation by tyrosine kinase). However, this activation requires
      lipophilic substrate (PI) present because cIP hydrolysis is not enhanced in the
      presence of PA.

PMID- 9915812
TI  - Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor.
      Structure-activity relationship of 2-arachidonoylglycerol, ether-linked
      analogues, and related compounds.
AB  - An endogenous cannabimimetic molecule, 2-arachidonoylglycerol, induces a rapid,
      transient increase in intracellular free Ca2+ concentrations in NG108-15 cells
      through a cannabinoid CB1 receptor-dependent mechanism. We examined the
      activities of 24 relevant compounds (2-arachidonoylglycerol, its structural
      analogues, and several synthetic cannabinoids). We found that 2
      arachidonoylglycerol is the most potent compound examined so far: its activity
      was detectable from as low as 0.3 nM, and the maximal response induced by 2
      arachidonoylglycerol exceeded the responses induced by others. Activities of HU
      210 and CP55940, potent cannabinoid receptor agonists, were also detectable from
      as low as 0.3 nM, whereas the maximal responses induced by these compounds were
      low compared with 2-arachidonoylglycerol. Anandamide was also found to act as a
      partial agonist in this assay system. We confirmed that free arachidonic acid
      failed to elicit a response. Furthermore, we found that a metabolically stable
      ether-linked analogue of 2-arachidonoylglycerol possesses appreciable agonistic
      activity, although its activity was apparently lower than that of 2
      arachidonoylglycerol. We also confirmed that pretreating cells with various
      cannabinoid receptor agonists nullified the response induced by 2
      arachidonoylglycerol, whereas pretreating cells with other neurotransmitters or
      neuromodulators did not affect the response. These results strongly suggested
      that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol
      receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for
      the cannabinoid CB1 receptor.

PMID- 9915813
TI  - Characterization of disulfide cross-links between fragments of proteolyzed Na,K
      ATPase. Implications for spatial organization of trans-membrane helices.
AB  - This study characterizes disulfide cross-links between fragments of a well
      defined tryptic preparation of Na,K-ATPase, 19-kDa membranes solubilized with
      C12E10 in conditions preserving an intact complex of fragments and Rb occlusion
      (Or, E., Goldshleger, R., Tal, D. M., and Karlish, S. J. D. (1996) Biochemistry
      35, 6853-6864). Upon solubilization, cross-links form spontaneously between the
      beta subunit, 19- and 11.7-kDa fragments of the alpha subunit, containing trans
      membrane segments M7-M10 and M1/M2, respectively. Treatment with Cu2+
      phenanthroline (CuP) improves efficiency of cross-linking. Sequencing and
      immunoblot analysis have shown that the cross-linked products consist of a
      mixture of beta-19 kDa dimers ( approximately 65%) and beta-19 kDa-11.7 kDa
      trimers ( approximately 35%). The alpha-beta cross-link has been located within
      the 19-kDa fragment to a 6.5-kDa chymotryptic fragment containing M8, indicating
      that betaCys44 is cross-linked to either Cys911 or Cys930. In addition, an
      internal cross-link between M9 and M10, Cys964-Cys983, has been found by
      sequencing tryptic fragments of the cross-linked product. The M1/M2-M7/M10 cross
      link has not been identified directly. However, we propose that Cys983 in M10 is
      cross-linked either to Cys104 in M1 or internally to Cys964 in M9. Based on this
      study, cross-linking induced by o-phthalaldehyde (Or, E., Goldshleger, R., and
      Karlish, S. J. D. (1998) Biochemistry 37, 8197-8207), and information from the
      literature, we propose an approximate spatial organization of trans-membrane
      segments of the alpha and beta subunits.

PMID- 9915814
TI  - Tissue inhibitor of metalloproteinases-3 inhibits shedding of L-selectin from
      leukocytes.
AB  - Although the enzyme or enzymes mediating shedding of L-selectin have not yet been
      identified, this activity can be blocked by synthetic hydroxamic acid-based
      inhibitors of metalloproteinases such as Ro 31-9790. However, the endogenous
      matrix metalloproteinase inhibitor tissue inhibitor of metalloproteinases (TIMP)
      1 does not block L-selectin shedding. Here, we report that TIMP-3, but not TIMP
      2, inhibits L-selectin shedding from mouse and human lymphocytes, Jurkat T cells,
      and human monocytes. TIMP-3 has an IC50 of 0.3-0.4 microM on these cell types
      compared with 0.7-4.8 microM for Ro 31-9790. A metalloproteinase (tumor necrosis
      factor-alpha (TNF-alpha)-converting enzyme; ADAM17) has recently been identified
      which cleaves the pro-form of TNF-alpha to produce soluble cytokine. We compared
      inhibition of L-selectin shedding by TIMPs and Ro 31-9790 with inhibition of TNF
      alpha shedding from human monocytes. TIMP-3 inhibited TNF-alpha shedding (IC50 of
      0.1 microM), as did Ro 31-9790 (IC50 of 0.4 microM). TIMP-2 had a partial effect,
      and TIMP-1 did not inhibit. This study confirms that L-selectin sheddase is a
      metalloproteinase, but not a matrix metalloproteinase, and investigates the
      relationship between shedding of L-selectin and TNF-alpha.

PMID- 9915815
TI  - Insertion of a bacterial secondary transport protein in the endoplasmic reticulum
      membrane.
AB  - The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains
      12 hydrophobic potential transmembrane domains. Surprisingly, an alkaline
      phosphatase fusion study in Escherichia coli has suggested that only 9 of these
      domains are embedded in the membrane, and 3 are translocated to the periplasm
      (van Geest, M., and Lolkema, J. S. (1996) J. Biol. Chem. 271, 25582-25589). To
      provide independent data on the topology and mode of membrane insertion of CitS,
      we have investigated its insertion into the endoplasmic reticulum (ER) membrane.
      By using in vitro translation of model proteins in the presence of dog pancreas
      microsomes, each of the putative transmembrane segments of CitS was assayed for
      its potency to insert into the ER membrane, both as an isolated segment as well
      as in the context of COOH-terminal truncation mutants. All 12 segments were able
      to insert into the membrane as Ncyt-Clum signal anchor sequences. In a series of
      COOH-terminal truncation mutants, the segments inserted in a sequential way
      except for one segment, segment Vb, which was translocated to the lumen.
      Hydrophobic segments VIII and IX, which, according to the alkaline phosphatase
      fusion study, are in the periplasm of E. coli, form a helical hairpin in the ER
      membrane. These observations suggest a topology for CitS with 11 transmembrane
      segments and also demonstrate that the sequence requirements for signal anchor
      and stop transfer function are different.

PMID- 9915816
TI  - Galphai is not required for chemotaxis mediated by Gi-coupled receptors.
AB  - Pertussis toxin inhibits chemotaxis of neutrophils by preventing chemoattractant
      receptors from activating trimeric G proteins in the Gi subfamily. In HEK293
      cells expressing recombinant receptors, directional migration toward appropriate
      agonist ligands requires release of free G protein betagamma subunits and can be
      triggered by agonists for receptors coupled to Gi but not by agonists for
      receptors coupled to two other G proteins, Gs and Gq. Because activation of any G
      protein presumably releases free Gbetagamma, we tested the hypothesis that
      chemotaxis also requires activated alpha subunits (Galphai) of Gi proteins.
      HEK293 cells were stably cotransfected with the Gi-coupled receptor for
      interleukin-8, CXCR1, and with a chimeric Galpha, Galphaqz5, which resembles
      Galphai in susceptibility to activation by Gi-coupled receptors but cannot
      regulate the Galphai effector, adenylyl cyclase. These cells, unlike cells
      expressing CXCR1 alone, migrated toward interleukin-8 even after treatment with
      pertussis toxin, which prevents activation of endogenous Galphai but not that of
      Galphaqz5. We infer that chemotaxis does not require activation of Galphai.
      Because chemotaxis is mediated by Gbetagamma subunits released when Gi-coupled
      receptors activate Galphaqz5, but not when Gq- or Gs-coupled receptors activate
      their respective G proteins, we propose that Gi-coupled receptors transmit a
      necessary chemotactic signal that is independent of Galphai.

PMID- 9915817
TI  - Insulin-like growth factor I-mediated activation of the transcription factor cAMP
      response element-binding protein in PC12 cells. Involvement of p38 mitogen
      activated protein kinase-mediated pathway.
AB  - IGF-I is known to support growth and to prevent apoptosis in neuronal cells.
      Activation of the nuclear transcription factor cAMP response element-binding
      protein (CREB) has emerged as a central determinant in neuronal functions. In the
      present investigation, we examined the IGF-I-mediated phosphorylation and
      transcriptional activation of CREB in rat pheochromocytoma (PC12) cells, a
      cellular model for neuronal differentiation, and defined three distinct
      postreceptor signaling pathways important for this effect including the p38
      mitogen-activated protein kinase (MAPK) pathway. CREB phosphorylation at serine
      133 and its transcriptional activation as measured by a CREB-specific Gal4-CREB
      reporter and the neuroendocrine-specific gene chromogranin A was induced 2-3.3
      fold by insulin-like growth factor (IGF)-I. This activation was significantly
      blocked (p < 0.001) by the dominant negative K-CREB or by mutation of the CRE
      site. IGF-I stimulated chromogranin A gene expression by Northern blot analysis
      3.7-fold. Inhibition of MAPK kinase with PD98059, PI 3-kinase with wortmannin,
      and p38 MAPK with SB203580 blocked IGF-I-mediated phosphorylation and
      transcriptional activation of CREB by 30-50% (p < 0.001). Constitutively active
      and dominant negative regulators of the Ras and PI 3-kinase pathways confirmed
      the contribution of these pathways for CREB regulation by IGF-I. Cotransfection
      of PC12 cells with p38beta and constitutively active MAPK kinase 6 resulted in
      enhanced basal as well as IGF-I-stimulated chromogranin A promoter. IGF-I
      activated p38 MAPK, which was blocked by the inhibitor SB203580. This is the
      first description of a p38 MAPK-mediated nuclear signaling pathway for IGF-I
      leading to CREB-dependent neuronal specific gene expression.

PMID- 9915818
TI  - Effects of the location of distal histidine in the reaction of myoglobin with
      hydrogen peroxide.
AB  - To clarify how the location of distal histidine affects the activation process of
      H2O2 by heme proteins, we have characterized reactions with H2O2 for the
      L29H/H64L and F43H/H64L mutants of sperm whale myoglobin (Mb), designed to locate
      the histidine farther from the heme iron. Whereas the L29H/H64L double
      substitution retarded the reaction with H2O2, an 11-fold rate increase versus
      wild-type Mb was observed for the F43H/H64L mutant. The Vmax values for 1
      electron oxidations by the myoglobins correlate well with the varied reactivities
      with H2O2. The functions of the distal histidine as a general acid-base catalyst
      were examined based on the reactions with cumene hydroperoxide and cyanide, and
      only the histidine in F43H/H64L Mb was suggested to facilitate heterolysis of the
      peroxide bond. The x-ray crystal structures of the mutants confirmed that the
      distal histidines in F43H/H64L Mb and peroxidase are similar in distance from the
      heme iron, whereas the distal histidine in L29H/H64L Mb is located too far to
      enhance heterolysis. Our results indicate that the proper positioning of the
      distal histidine is essential for the activation of H2O2 by heme enzymes.

PMID- 9915819
TI  - Characterization of the elastin binding domain in the cell-surface 25-kDa elastin
      binding protein of staphylococcus aureus (EbpS).
AB  - Our previous studies have established that a cell-surface 25-kDa elastin-binding
      protein of Staphylococcus aureus (EbpS) mediates binding of this pathogen to the
      extracellular matrix protein elastin. Results from binding assays examining the
      activity of various EbpS fragments suggested that the elastin recognition domain
      is contained within the first 59 amino acids. In this report, we have used
      functional analyses with synthetic peptides and recombinant truncated forms of
      EbpS to localize the elastin binding domain to a 21-amino acid region contained
      within residues 14-34 of EbpS. Further evidence for the importance of this domain
      was obtained by demonstrating that the inhibitory activity of anti-EbpS
      antibodies on staphylococcal elastin binding was neutralized when these
      antibodies were pre-absorbed with a truncated recombinant EbpS construct
      containing residues 1-34. Overlapping synthetic peptides corresponding to EbpS
      residues 14-36 were then generated and tested for elastin binding activity to
      define further the elastin binding domain, and results from these studies showed
      that sequences spanning amino acids Gln14-Asp23, Asp17-Asp23, and Thr18-Glu34
      inhibit binding of Staphylococcus aureus to elastin. Our analyses indicate that
      the hexameric sequence Thr18-Asn-Ser-His-Gln-Asp23 is the minimal sequence common
      to all active synthetic peptides, proteolytic fragments, and recombinant
      constructs of EbpS. Furthermore, substitution of Asp23 with Asn abrogated the
      blocking activity of the synthetic peptides, demonstrating the requirement for a
      charged amino acid at this location. The composite data indicate that
      staphylococcal elastin binding is mediated by a discrete domain defined by short
      peptide sequences in the amino-terminal extracellular region of EbpS.

PMID- 9915820
TI  - RGS16 attenuates galphaq-dependent p38 mitogen-activated protein kinase
      activation by platelet-activating factor.
AB  - The large gene family encoding the regulators of G protein signaling (RGS)
      proteins has been implicated in the fine tuning of a variety of cellular events
      in response to G protein-coupled receptor activation. Several studies have shown
      that the RGS proteins can attenuate G protein-activated extracellular signal
      regulated kinase (ERK) group of mitogen-activated protein kinases. We demonstrate
      herein that the production of inositol trisphosphate and the activation of the
      p38 group of mitogen-activated protein kinases by the G protein-coupled platelet
      activating factor (PAF) receptor was attenuated by RGS16 in both CHO cells
      transiently and stably expressing RGS16. The inhibition was not observed with
      RGS2, RGS5, and a functionally defective form of RGS16, RGS16(R169S/F170C). The
      PAF-induced p38 and ERK pathways appeared to be preferentially regulated by RGS16
      and RGS1, respectively. Overexpression of a constitutively active form of
      Galpha11 (Galpha11Q209L) prevented the RGS16-mediated attenuation of p38
      activity, suggesting that Galphaq/11 is involved in PAF activation of p38. The
      Galphaq/11 involvement is further supported by the observation that p38
      activation by PAF was pertussis toxin-insensitive. These results demonstrate for
      the first time that apart from ERK, p38 activation by a G protein-coupled
      receptor can be attenuated by an RGS protein and provide further evidence for the
      specificity of RGS function in G protein signaling pathways.

PMID- 9915821
TI  - Interaction of hepatitis B viral X protein and CCAAT/ enhancer-binding protein
      alpha synergistically activates the hepatitis B viral enhancer II/pregenomic
      promoter.
AB  - The hepatitis B viral X protein (HBx) is known to exert its transactivation
      activity by the interaction with several cellular transcription factors. Here we
      report the interaction of HBx and CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) and their effects on the enhancer/promoters of hepatitis B virus
      (HBV). A chloramphenicol acetyltransferase assay showed that the cotransfection
      of HBx and C/EBPalpha strongly activated the enhancer II/pregenomic promoter of
      HBV in a synergistic manner. This effect was also observed in the heterologous
      expression system with promoters of SV40 and herpes simplex virus thymidine
      kinase genes. Serial deletion analysis of the enhancer II/pregenomic promoter
      identified the responsible region (nucleotides 1639-1679), in which two C/EBP
      binding sites are located. An in vitro interaction assay and electrophoretic
      mobility shift assay showed that HBx augmented the DNA binding activity of
      C/EBPalpha by direct interaction with it, and its basic leucine zipper domain was
      responsible for the interaction with HBx. Domain analysis of HBx showed that the
      central region (amino acids 78-103) was necessary for direct interaction with
      C/EBPalpha. However, the complete form of HBx was necessary for the synergistic
      activation of the HBV pregenomic promoter. These results suggest that the
      interaction of HBx and C/EBPalpha enhances the transcription of the HBV
      pregenomic promoter for the effective life cycle of HBV in hepatocytes.

PMID- 9915822
TI  - Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide
      glutathione peroxidase. Isolation and enzymatic characterization of human
      selenoprotein p.
AB  - Selenoprotein P is an extracellular protein containing presumably 10
      selenocysteines that are encoded by the UGA stop codon in the open reading frame
      of the mRNA. The function of selenoprotein P is currently unknown, although
      several indirect lines of evidence suggest that selenoprotein P is a free radical
      scavenger. We first developed a conventional procedure to isolate selenoprotein P
      from human plasma. Next, we investigated the reactivities of selenoprotein P
      against various hydroperoxides in the presence of glutathione. Although
      selenoprotein P reduces neither hydrogen peroxide nor tertiary butyl
      hydroperoxide, it does reduce phospholipid hydroperoxide such as 1-palmitoyl-2
      (13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-3-phosphatidylcholine
      hydroperoxide. Kinetic analysis demonstrated a tert-uni ping-pong mechanism,
      similar to those described for classical glutathione peroxidase and phospholipid
      hydroperoxide glutathione peroxidase. Not only glutathione, but also
      dithiothreitol, mercaptoethanol, cysteine, and homocysteine, were effective as
      reducing substances, as in the case of phospholipid hydroperoxide glutathione
      peroxidase. These results show that selenoprotein P functions as a phospholipid
      hydroperoxide glutathione peroxidase in extracellular fluids.

PMID- 9915823
TI  - A novel phospholipase C delta4 (PLCdelta4) splice variant as a negative regulator
      of PLC.
AB  - It has been reported that there are two alternatively spliced variants of
      phospholipase C-delta4 (PLCdelta4), termed ALT I and II, that contain an
      additional 32 and 14 amino acids in their respective sequences in the linker
      region between the catalytic X and Y domains (Lee, S. B., and Rhee, S. G. (1996)
      J. Biol. Chem. 271, 25-31). We report here the isolation and characterization of
      a novel alternative splicing isoform of PLCdelta4, termed ALT III, as a negative
      regulator of PLC. In ALT III, alternative splicing occurred in the catalytic X
      domain, i.e. 63 amino acids (residues 424-486) containing the C-terminal of the X
      domain and linker region were substituted for 32 amino acids corresponding to the
      insert sequence of ALT I. Although the expression level of ALT III was found to
      be much lower in most tissues and cells compared with that of PLCdelta4, it was
      significantly higher in some neural cells, such as NIE-115 cells and p19 cells
      differentiated to neural cells by retinoic acid. Interestingly, recombinant ALT
      III protein did not retain enzymatic activity, and the activity of PLCdelta4
      overexpressed in COS7 cells was markedly decreased by the co-expression of ALT
      III but not by ALT I or II. Moreover, N-terminal pleckstrin homology domain (PH
      domain) of ALT III alone could inhibit the increase of inositol-1,4, 5
      trisphosphate levels in PLCdelta4-overexpressing NIH3T3 cells, whereas a PH
      domain deletion mutant could not, indicating that the PH domain is necessary and
      sufficient for its inhibitory effect. The ALT III PH domain specifically bound to
      phosphatidylinositol (PtdIns)-4,5-P2 and PtdIns-3,4,5-P3 but not PtdIns, PtdIns-4
      P, or inositol phosphates, and the mutant R36G, which retained only weak affinity
      for PtdIns-4,5-P2, could not inhibit the activity of PLCdelta4. These results
      indicate that PtdIns-4,5-P2 binding to PH domain is essential for the inhibitory
      effect of ALT III. ALT III also inhibited PLCdelta1 activity and partially
      suppressed PLCgamma1 activity, but not PLCbeta1 in vitro; it did inhibit all
      types of isozymes tested in vivo. Taken together, our results indicate that ALT
      III is a negative regulator of PLC that is most effective against the PLC delta
      type isozymes, and its PH domain is essential for its function.

PMID- 9915824
TI  - Insulin promotes phosphorylation and activation of geranylgeranyltransferase II.
      Studies with geranylgeranylation of rab-3 and rab-4.
AB  - Rab proteins play a crucial role in the trafficking of intracellular vesicles.
      Rab proteins are GTPases that cycle between an inactive GDP-bound form and an
      active GTP-bound conformation. A prerequisite to Rab activation by GTP loading is
      its post-translational modification by the addition of geranylgeranyl moieties to
      highly conserved C-terminal cysteine residues. We examined the effect of insulin
      on the activity of geranylgeranyltransferase II (GGTase II) in 3T3-L1 fibroblasts
      and adipocytes. In fibroblasts, insulin increased the enzymatic activity of
      GGTase II 2.5-fold after 1 h of incubation, an effect that is blocked by perillyl
      alcohol, an inhibitor of prenyltransferases, but not by the
      geranylgeranyltransferase I inhibitor, GGTI-298, or the farnesyltransferase
      inhibitor, alpha-hydroxyfarnesylphosphonic acid. Concomitantly, insulin
      stimulated the phosphorylation of the GGTase II alpha-subunit without any effect
      on the GGTase II beta-subunit. At the same time, insulin also increased the
      amounts of geranylgeranylated Rab-3 in 3T3-L1 fibroblasts from 44 +/- 1.2% in
      control cells to 63 +/- 3.8 and 64 +/- 6.1% after 1 and 24 h of incubation,
      respectively. In adipocytes, insulin increased the amounts of geranylgeranylated
      Rab-4 from 38 +/- 0.6% in control cells to 56 +/- 1.7 and 60 +/- 2.6% after 1 and
      24 h of incubation, respectively. In both fibroblasts and adipocytes, the
      presence of perillyl alcohol blocked the ability of insulin to increase
      geranylgeranylation of Rab-4, whereas GGTI-298 and alpha
      hydroxyfarnesylphosphonic acid were without effect, indicating that insulin
      activates GGTase II. In summary, insulin promotes phosphorylation and activation
      of GGTase II in both 3T3 L1 fibroblasts and adipocytes and increases the amounts
      of geranylgeranylated Rab-3 and Rab-4 proteins.

PMID- 9915826
TI  - Identification of an extracellular signal-regulated kinase (ERK) docking site in
      ribosomal S6 kinase, a sequence critical for activation by ERK in vivo.
AB  - Glutathione S-transferase (GST)-fusion proteins containing the carboxyl-terminal
      tails of three p90 ribosomal S6 kinase (RSK) isozymes (RSK1, RSK2, and RSK3)
      interacted with extracellular signal-regulated kinase (ERK) but not c-Jun-NH2
      kinase (JNK) or p38 mitogen-activated protein kinase (MAPK). Within the carboxyl
      terminal residues of the RSK isozymes is a region of high conservation
      corresponding to residues 722LAQRRVRKLPSTTL735 in RSK1. Truncation of the
      carboxyl-terminal 9 residues, 727VRKLPSTTL735, completely eliminated the
      interaction of the GST-RSK1 fusion protein with purified recombinant ERK2,
      whereas the truncation of residues 731PSTTL735 had no effect on the interaction
      with purified ERK2. ERK1 and ERK2 co-immunoprecipitated with hemagglutinin-tagged
      wild type RSK2 (HA-RSK2) in BHK cell cytosol. However, ERK did not co
      immunoprecipitate with HA-RSK2((1-729)), a mutant missing the carboxyl-terminal
      11 amino acids, similar to the minimal truncation that eliminated in vitro
      interaction of ERK with the GST-RSK1 fusion protein. Kinase activity of HA-RSK2
      increased 6-fold in response to insulin. HA-RSK2((1-729)) had a similar basal
      kinase activity to that of HA-RSK2 but was not affected by insulin treatment.
      Immunoprecipitated HA-RSK2 and HA-RSK2((1-729)) could be activated to the same
      extent in vitro by active ERK2, demonstrating that HA-RSK2((1-729)) was properly
      folded. These data suggest that the conserved region of the RSK isozymes
      (722LAQRRVRKL730 of RSK1) provides for a specific ERK docking site approximately
      150 amino acids carboxyl-terminal to the nearest identified ERK phosphorylation
      site (Thr573). Complex formation between RSK and ERK is essential for the
      activation of RSK by ERK in vivo. Comparison of the docking site of RSK with the
      carboxyl-terminal tails of other MAPK-activated kinases reveals putative docking
      sites within each of these MAPK-targeted kinases. The number and placement of
      lysine and arginine residues within the conserved region correlate with
      specificity for activation by ERK and p38 MAPKs in vivo.

PMID- 9915827
TI  - Proteolytic dissection of Zab, the Z-DNA-binding domain of human ADAR1.
AB  - Zalpha is a peptide motif that binds to Z-DNA with high affinity. This motif
      binds to alternating dC-dG sequences stabilized in the Z-conformation by means of
      bromination or supercoiling, but not to B-DNA. Zalpha is part of the N-terminal
      region of double-stranded RNA adenosine deaminase (ADAR1), a candidate enzyme for
      nuclear pre-mRNA editing in mammals. Zalpha is conserved in ADAR1 from many
      species; in each case, there is a second similar motif, Zbeta, separated from
      Zalpha by a more divergent linker. To investigate the structure-function
      relationship of Zalpha, its domain structure was studied by limited proteolysis.
      Proteolytic profiles indicated that Zalpha is part of a domain, Zab, of 229 amino
      acids (residues 133-361 in human ADAR1). This domain contains both Zalpha and
      Zbeta as well as a tandem repeat of a 49-amino acid linker module. Prolonged
      proteolysis revealed a minimal core domain of 77 amino acids (positions 133-209),
      containing only Zalpha, which is sufficient to bind left-handed Z-DNA; however,
      the substrate binding is strikingly different from that of Zab. The second motif,
      Zbeta, retains its structural integrity only in the context of Zab and does not
      bind Z-DNA as a separate entity. These results suggest that Zalpha and Zbeta act
      as a single bipartite domain. In the presence of substrate DNA, Zab becomes more
      resistant to proteases, suggesting that it adopts a more rigid structure when
      bound to its substrate, possibly with conformational changes in parts of the
      protein.

PMID- 9915825
TI  - Retinoid isomers differ in the ability to induce release of SMRT corepressor from
      retinoic acid receptor-alpha.
AB  - Nuclear hormone receptors are ligand-regulated transcription factors that
      modulate the expression of specific target genes in response to the binding of
      small, hydrophobic hormone ligands. Many nuclear hormone receptors, such as the
      retinoic acid receptors, can both repress and activate target gene expression;
      these bimodal transcription properties are mediated by the ability of these
      receptors to tether auxiliary factors, denoted corepressors and coactivators.
      Corepressors are typically bound by receptors in the absence of cognate hormone,
      whereas binding of an appropriate hormone agonist induces an allosteric
      alteration in the receptor resulting in release of the corepressor and
      recruitment of coactivator. Structural analysis indicates that there is a close
      induced fit between the hormone ligand and the receptor polypeptide chain. This
      observation suggests that different ligands, once bound, may confer distinct
      conformations on the receptor that may invoke, in turn, distinct functional
      consequences. We report here that different retinoids do differ in the ability to
      release corepressor once bound to retinoic acid receptor and suggest that these
      differences in corepressor release may manifest as differences in transcriptional
      regulation.

PMID- 9915828
TI  - The DNA binding properties of Saccharomyces cerevisiae Rad51 protein.
AB  - Saccharomyces cerevisiae Rad51 protein is the paradigm for eukaryotic ATP
      dependent DNA strand exchange proteins. To explain some of the unique
      characteristics of DNA strand exchange promoted by Rad51 protein, when compared
      with its prokaryotic homologue the Escherichia coli RecA protein, we analyzed the
      DNA binding properties of the Rad51 protein. Rad51 protein binds both single
      stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in an ATP- and Mg2+
      dependent manner, over a wide range of pH, with an apparent binding stoichiometry
      of approximately 1 protein monomer per 4 (+/-1) nucleotides or base pairs,
      respectively. Only dATP and adenosine 5'-gamma-(thiotriphosphate) (ATPgammaS) can
      substitute for ATP, but binding in the presence of ATPgammaS requires more than a
      5-fold stoichiometric excess of protein. Without nucleotide cofactor, Rad51
      protein binds both ssDNA and dsDNA but only at pH values lower than 6.8; in this
      case, the apparent binding stoichiometry covers the range of 1 protein monomer
      per 6-9 nucleotides or base pairs. Therefore, Rad51 protein displays two distinct
      modes of DNA binding. These binding modes are not inter-convertible; however,
      their initial selection is governed by ATP binding. On the basis of these DNA
      binding properties, we conclude that the main reason for the low efficiency of
      the DNA strand exchange promoted by Rad51 protein in vitro is its enhanced dsDNA
      binding ability, which inhibits both the presynaptic and synaptic phases of the
      DNA strand exchange reaction as follows: during presynapsis, Rad51 protein
      interacts with and stabilizes secondary structures in ssDNA thereby inhibiting
      formation of a contiguous nucleoprotein filament; during synapsis, Rad51 protein
      inactivates the homologous dsDNA partner by directly binding to it.

PMID- 9915829
TI  - Hydroxide rather than histidine is coordinated to the heme in five-coordinate
      ferric Scapharca inaequivalvis hemoglobin.
AB  - The ferric form of the homodimeric Scapharca hemoglobin undergoes a pH-dependent
      spin transition of the heme iron. The transition can also be modulated by the
      presence of salt. From our earlier studies it was shown that three distinct
      species are populated in the pH range 6-9. At acidic pH, a low-spin six
      coordinate structure predominates. At neutral and at alkaline pHs, in addition to
      a small population of a hexacoordinate high-spin species, a pentacoordinate
      species is significantly populated. Isotope difference spectra clearly show that
      the heme group in the latter species has a hydroxide ligand and thereby is not
      coordinated by the proximal histidine. The stretching frequency of the Fe-OH
      moiety is 578 cm-1 and shifts to 553 cm-1 in H218O, as would be expected for a Fe
      OH unit. On the other hand, the ferrous form of the protein shows substantial
      stability over a wide pH range. These observations suggest that Scapharca
      hemoglobin has a unique heme structure that undergoes substantial redox-dependent
      rearrangements that stabilize the Fe-proximal histidine bond in the functional
      deoxy form of the protein but not in the ferric form.

PMID- 9915830
TI  - Desensitization of catecholamine release. The novel catecholamine release
      inhibitory peptide catestatin (chromogranin a344-364) acts at the receptor to
      prevent nicotinic cholinergic tolerance.
AB  - Nicotinic cholinergic receptors undergo desensitization upon repeated or
      prolonged exposure to agonist. We investigated the effects of a novel
      chromogranin A catecholamine release-inhibitory fragment, catestatin
      (chromogranin A344-364), on agonist-induced desensitization of catecholamine
      release from pheochromocytoma cells. In a dose-dependent fashion, the nicotinic
      antagonist catestatin blocked agonist desensitization of both catecholamine
      release (IC50 approximately 0.24 microM) and 22Na+ uptake (IC50 approximately
      0.31 microM), the initial step in nicotinic cationic signal transduction; both
      secretion inhibition and blockade of desensitization were noncompetitive with
      agonist. Desensitizing effects of the nicotinic agonists nicotine and epibatidine
      were blocked. This antagonist action was specific to desensitization by nicotinic
      agonists, since catestatin did not block desensitization of catecholamine release
      induced by agents which bypass the nicotinic receptor. Hill plots with slopes
      near unity suggested noncooperativity for catestatin effects on both nicotinic
      responses (secretory antagonism and blockade of desensitization). Human, bovine,
      and rat catestatins (as well as substance P) had similar potencies. IC50 values
      for secretion inhibition and blockade of desensitization paralleled each other (r
      = 0.76, n = 10 antagonists, p = 0.01) for several noncompetitive nicotinic
      antagonists. Peptide nicotinic antagonists (catestatins, substance P) were far
      more potent inhibitors of both secretion (p = 0.019) and desensitization (p =
      0.005) than nonpeptide antagonists (trimethaphan, hexamethonium, procaine,
      phencyclidine, cocaine, or clonidine), and the peptides displayed enhanced
      selectivity to block desensitization versus secretion (p = 0.003). We conclude
      that catestatin is a highly potent, dose-dependent, noncompetitive,
      noncooperative, specific inhibitor of nicotinic desensitization, an effect which
      may have implications for control of catecholamine release.

PMID- 9915831
TI  - Kalirin, a multifunctional PAM COOH-terminal domain interactor protein, affects
      cytoskeletal organization and ACTH secretion from AtT-20 cells.
AB  - The production and regulated secretion of bioactive peptides require a series of
      lumenal enzymes to convert inactive precursors into bioactive peptides plus
      several cytosolic proteins to govern granule formation, maturation,
      translocation, and exocytosis. Peptidylglycine alpha-amidating monooxygenase
      (PAM), an enzyme essential for biosynthesis of many peptides, is an integral
      membrane protein with trafficking information in both its lumenal and cytosolic
      domains. Kalirin, a PAM cytosolic domain interactor protein with spectrin-like
      repeats and GDP/GTP exchange factor activity for Rac1, is expressed with PAM in
      neurons but is not expressed in the anterior pituitary or AtT-20 corticotrope
      cells. Expression of Kalirin alters the cytoskeletal organization of Chinese
      hamster ovary and AtT-20 cells expressing membrane PAM. Expression of membrane
      PAM also alters cytoskeletal organization, demonstrating the presence of
      endogenous proteins that can mediate this effect. Significant amounts of both PAM
      and Kalirin fractionate with cytoskeletal elements. Since cytoskeletal
      organization is critical for exocytosis, constitutive-like and regulated
      secretions were evaluated. Whereas the constitutive-like secretion of
      adrenocorticotropic hormone (ACTH) is increased by expression of membrane PAM,
      regulated secretion is eliminated. Expression of Kalirin in AtT-20 cells
      expressing membrane PAM restores stimulated secretion of ACTH. Thus, Kalirin or
      its homologue may be essential for regulated secretion, and the PAM-Kalirin
      interaction may coordinate intragranular with cytosolic events.

PMID- 9915832
TI  - Cloning and characterization of PRAX-1. A new protein that specifically interacts
      with the peripheral benzodiazepine receptor.
AB  - Using a cytoplasmic domain of the peripheral benzodiazepine receptor (PBR) as a
      bait in the yeast two-hybrid system, we have isolated a cDNA encoding a new
      protein that specifically interacts with PBR. We named it PRAX-1, for peripheral
      benzodiazepine receptor-associated protein 1. PRAX-1 is a 1857-amino acid
      protein, the sequence of which was structurally unrelated to any known proteins.
      The gene encoding PRAX-1 is located in the q22-q23 region of the long arm of the
      human chromosome 17. The PRAX-1 mRNA is 7.5 kilobase pairs, predominantly
      expressed in the central nervous system, pituitary gland, and thymus. At the
      protein level, we found the PRAX-1 as a single 220-250-kDa protein in the brain
      and in many different human cell lines tested using specific antibody raised
      against PRAX-1. Parallel analysis of the PRAX-1 mRNA and protein expression
      performed in mouse and rat gave similar results. Immunocytochemistry analysis
      carried out to define the distribution of the PRAX-1 protein in the rat brain
      showed that PRAX-1 was prevalent in the mesolimbic system, specially abundant in
      the CA1 subfield of the hippocampus. Exhibiting several domains involved in
      protein-protein interaction (three proline-rich domains, three leucine-zipper
      motifs, and an Src homology region 3-like domain), the PRAX-1 may be looked upon
      as a new adaptator protein. We show that both the Src homology region 3-like
      domain and a proline-rich domain in PRAX-1 are required for the interaction with
      PBR. PRAX-1 is a cytoplasmic protein that also partially colocalizes with PBR in
      the mitochondria, as determined by confocal microscopy and Western blotting.
      Altogether our observations support a model of interaction implicating PBR and
      this newly described protein, PRAX-1. As being the first cytoplasmic protein
      associated with PBR, PRAX-1 is a new tool that opens new fields for exploring PBR
      biological roles.

PMID- 9915833
TI  - Identification and characterization of golgin-84, a novel Golgi integral membrane
      protein with a cytoplasmic coiled-coil domain.
AB  - The cytoplasmic face of the Golgi contains a variety of proteins with coiled-coil
      domains. We identified one such protein in a yeast two-hybrid screen, using as
      bait the peripheral Golgi phosphatidylinositol(4,5)P2 5-phosphatase OCRL1 that is
      implicated in a human disease, the oculocerebrorenal syndrome. The approximately
      2.8-kilobase mRNA is ubiquitously expressed and abundant in testis; it encodes a
      731-amino acid protein with a predicted mass of 83 kDa. Antibodies against the
      sequence detect a novel approximately 84-kDa Golgi protein we termed golgin-84.
      Golgin-84 is an integral membrane protein with a single transmembrane domain
      close to its C terminus. In vitro, the protein inserts post-translationally into
      microsomal membranes with an N-cytoplasmic and C-lumen orientation. Cross-linking
      indicates that golgin-84 forms dimers, consistent with the prediction of an
      approximately 400-residue dimerizing coiled-coil domain in its N terminus. The
      dimerization potential is supported by a data base search that showed that the N
      terminal 497 residues of golgin-84 contain a coiled-coil domain that when fused
      to the RET tyrosine kinase domain had the ability to activate it, forming the RET
      II oncogene. Data base searching also indicates golgin-84 is similar in structure
      and sequence to giantin, a membrane protein that tethers coatamer complex I
      vesicles to the Golgi.

PMID- 9915834
TI  - Crystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop
      in a tetrameric assembly.
AB  - The crystal structure of mouse acetylcholinesterase at 2.9-A resolution reveals a
      tetrameric assembly of subunits with an antiparallel alignment of two canonical
      homodimers assembled through four-helix bundles. In the tetramer, a short Omega
      loop, composed of a cluster of hydrophobic residues conserved in mammalian
      acetylcholinesterases along with flanking alpha-helices, associates with the
      peripheral anionic site of the facing subunit and sterically occludes the
      entrance of the gorge leading to the active center. The inverse loop-peripheral
      site interaction occurs within the second pair of subunits, but the peripheral
      sites on the two loop-donor subunits remain freely accessible to the solvent. The
      position and complementarity of the peripheral site-occluding loop mimic the
      characteristics of the central loop of the peptidic inhibitor fasciculin bound to
      mouse acetylcholinesterase. Tetrameric forms of cholinesterases are widely
      distributed in nature and predominate in mammalian brain. This structure reveals
      a likely mode of subunit arrangement and suggests that the peripheral site,
      located near the rim of the gorge, is a site for association of neighboring
      subunits or heterologous proteins with interactive surface loops.

PMID- 9915835
TI  - NMR solution structure of domain 1 of human annexin I shows an autonomous folding
      unit.
AB  - Annexins are excellent models for studying the folding mechanisms of multidomain
      proteins because they have four-eight homologous helical domains with low
      identity in sequence but high similarity in folding. The structure of an isolated
      domain 1 of human annexin I has been determined by NMR spectroscopy. The
      sequential assignments of the 1H, 13C, and 15N resonances of the isolated domain
      1 were established by multinuclear, multidimensional NMR spectroscopy. The
      solution structure of the isolated domain 1 was derived from 1,099 experimental
      NMR restraints using a hybrid distance geometry-simulated annealing protocol. The
      root mean square deviation of the ensemble of 20 refined conformers that
      represent the structure from the mean coordinate set derived from them was 0. 57
      +/- 0.14 A and 1.11 +/- 0.19 A for the backbone atoms and all heavy atoms,
      respectively. The NMR structure of the isolated domain 1 could be superimposed
      with a root mean square deviation of 1.36 A for all backbone atoms with the
      corresponding part of the crystal structure of a truncated human annexin I
      containing all four domains, indicating that the structure of the isolated domain
      1 is highly similar to that when it folded together with the other three domains.
      The result suggests that in contrast to isolated domain 2, which is largely
      unfolded in solution, isolated domain 1 constitutes an autonomous folding unit
      and interdomain interactions may play critical roles in the folding of annexin I.

PMID- 9915836
TI  - Complex formation between Azotobacter vinelandii ferredoxin I and its
      physiological electron donor NADPH-ferredoxin reductase.
AB  - In Azotobacter vinelandii, deletion of the fdxA gene, which encodes ferredoxin I
      (FdI), leads to activation of the expression of the fpr gene, which encodes NADPH
      ferredoxin reductase (FPR). In order to investigate the relationship of these two
      proteins further, the interactions of the two purified proteins have been
      examined. AvFdI forms a specific 1:1 cross-linked complex with AvFPR through
      ionic interactions formed between the Lys residues of FPR and Asp/Glu residues of
      FdI. The Lys in FPR has been identified as Lys258, a residue that forms a salt
      bridge with one of the phosphate oxygens of FAD in the absence of FdI. UV-Vis and
      circular dichroism data show that on binding FdI, the spectrum of the FPR flavin
      is hyperchromatic and red-shifted, confirming the interaction region close to the
      FAD. Cytochrome c reductase assays and electron paramagnetic resonance data show
      that electron transfer between the two proteins is pH-dependent and that the [3Fe
      4S]+ cluster of FdI is specifically reduced by NADPH via FPR, suggesting that the
      [3Fe-4S] cluster is near FAD in the complex. To further investigate the FPR:FdI
      interaction, the electrostatic potentials for each protein were calculated.
      Strongly negative regions around the [3Fe-4S] cluster of FdI are
      electrostatically complementary with a strongly positive region overlaying the
      FAD of FPR, centered on Lys258. These proposed interactions of FdI with FPR are
      consistent with cross-linking, peptide mapping, spectroscopic, and electron
      transfer data and strongly support the suggestion that the two proteins are
      physiological redox partners.

PMID- 9915837
TI  - Pyropheophorbide-a methyl ester-mediated photosensitization activates
      transcription factor NF-kappaB through the interleukin-1 receptor-dependent
      signaling pathway.
AB  - Pyropheophorbide-a methyl ester (PPME) is a second generation of photosensitizers
      used in photodynamic therapy. We demonstrated that PPME photosensitization
      activated NF-kappaB transcription factor in colon cancer cells. Unexpectedly,
      this activation occurred in two separate waves, i.e. a rapid and transient one
      and a second slower but sustained phase. The former was due to photosensitization
      by PPME localized in the cytoplasmic membrane which triggered interleukin-1
      receptor internalization and the transduction pathways controlled by the
      interleukin-1 type I receptor. Indeed, TRAF6 dominant negative mutant abolished
      NF-kappaB activation by PPME photosensitization, and TRAF2 dominant negative
      mutant was without any effect, and overexpression of IkappaB kinases increased
      gene transcription controlled by NF-kappaB. Oxidative stress was not likely
      involved in the activation. On the other hand, the slower and sustained wave
      could be the product of the release of ceramide through activation of the acidic
      sphingomyelinase. PPME localization within the lysosomal membrane could explain
      why ceramide acted as second messenger in NF-kappaB activation by PPME
      photosensitization. These data will allow a better understanding of the molecular
      basis of tumor eradication by photodynamic therapy, in particular the importance
      of the host cell response in the treatment.

PMID- 9915838
TI  - The functional role of CrkII in actin cytoskeleton organization and mitogenesis.
AB  - Crk is a member of a family of adapter proteins predominantly composed of Src
      homology 2 and 3 domains, whose role in signaling pathways is presently unclear.
      Using an in situ electroporation system which permits the introduction of
      glutathione S-transferase (GST) fusion proteins into cells, we found that c-CrkII
      bound to p130(cas), but not to paxillin in serum-starved rat-1 fibroblasts
      overexpressing the human insulin receptor (HIRc cells) in vivo. 17 nM insulin
      stimulation dissociated the binding of c-CrkII to p130(cas), whereas 13 nM
      insulin-like growth factor-I, 16 nM epidermal growth factor (EGF), and 10% serum
      each showed little or no effect. We found that stress fiber formation is
      consistent with a change in the p130(cas).c-CrkII interactions before and after
      growth factor stimulation. Microinjection of either GST-Crk-SH2 or -Crk-(N)SH3
      domains, or anti-Crk antibody each inhibited stress fiber formation before and
      after insulin-like growth factor-I, EGF, and serum stimulation. Insulin
      stimulation by itself caused stress fiber breakdown and there was no additive
      effect of microinjection. Microinjection of anti-p130(cas) antibody also blocked
      stress fiber formation in quiescent cells. Microinjection of the Crk-inhibitory
      reagents also inhibited DNA synthesis after insulin-like growth factor-I, EGF,
      and serum stimulation, but not after insulin. These data suggest that the complex
      containing p130(cas).c-CrkII may play a crucial role in actin cytoskeleton
      organization and in anchorage-dependent DNA synthesis.

PMID- 9915839
TI  - 4F2 (CD98) heavy chain is associated covalently with an amino acid transporter
      and controls intracellular trafficking and membrane topology of 4F2 heterodimer.
AB  - 4F2, also termed CD98, is an integral membrane protein consisting of a heavy
      chain linked to a light chain by disulfide bond. We have generated a monoclonal
      antibody to the mouse 4F2 light chain and cloned the cDNA. It encodes a mouse
      counterpart of rat L-type amino acid transporter-1, and induces system L amino
      acid transport in Xenopus oocytes in the presence of 4F2 heavy chain.
      Transfection studies in mammalian cells have indicated that the 4F2 heavy chain
      is expressed on the plasma membrane on its own, whereas the 4F2 light chain can
      be transported to the surface only in the presence of 4F2 heavy chain. 4F2 heavy
      chain is expressed diffusely on the surface of fibroblastic L cells, whereas it
      is localized selectively to the cell-cell adhesion sites in L cells expressing
      cadherins. These results indicate that the 4F2 heavy chain is associated
      covalently with an amino acid transporter and controls the cell surface
      expression as well as the membrane topology of the 4F2 heterodimer. Although 4F2
      heavy and light chains are expressed coordinately in most tissues, the light
      chain is barely detected by the antibody in kidney and intestine, despite the
      presence of heavy chain in a complex form. The results predict the presence of
      multiple 4F2 light chains.

PMID- 9915840
TI  - Isolation, cloning, and characterization of a new mammalian coronin family
      member, coroninse, which is regulated within the protein kinase C signaling
      pathway.
AB  - In order to understand the regulatory role of protein kinase C (PKC) in secretory
      epithelia, it is necessary to identify and characterize specific downstream
      targets. We previously identified one such protein in studies of gastric parietal
      cells. This protein was referred to as pp66 because it migrated with an apparent
      molecular mass of 66 kDa on SDS-polyacrylamide gels. The phosphorylation of pp66
      is increased by the cholinergic agonist, carbachol, and by the PKC activator,
      phorbol-12-myristate-13-acetate, in a calcium-independent manner. In this study,
      we have purified pp66 to homogeneity and cloned the complete open reading frame.
      GenBankTM searches revealed a 45% homology with the Dictyostelium actin-binding
      protein, coronin, and approximately 67% homology with the previously cloned human
      and bovine coronin-like homologue, p57. pp66 appears to be most highly expressed
      in the gastrointestinal mucosa and in kidney and lung. Confocal microscopic
      studies of an enhanced green fluorescent protein fusion construct of pp66 in
      cultured parietal cells and in Madin-Darby canine kidney cells indicate that pp66
      preferentially localizes in F-actin-rich regions. On the basis of our findings,
      we propose that pp66 may play an important, PKC-dependent role in regulating
      membrane/cytoskeletal rearrangements in epithelial cells. We have tentatively
      named this protein coroninse, because it appears to be highly expressed in
      secretory epithelia.

PMID- 9915841
TI  - The ligand-induced structural changes of human L-Arginine:Glycine
      amidinotransferase. A mutational and crystallographic study.
AB  - Human L-arginine:glycine amidinotransferase (AT) shows large structural changes
      of the 300-flap and of helix H9 upon binding of L-arginine and L-ornithine,
      described as a closed and an open conformation (Humm, A., Fritsche, E.,
      Steinbacher, S., and Huber, R. (1997) EMBO J. 16, 3373-3385). To elucidate the
      structural basis of these induced-fit movements, the x-ray structures of AT in
      complex with the amidino acceptor glycine and its analogs gamma-aminobutyric acid
      and delta-aminovaleric acid, as well as in complex with the amidino donor analogs
      L-alanine, L-alpha-aminobutyric acid, and L-norvaline, have been solved at 2.6-,
      2.5-, 2.37-, 2.3-, 2.5-, and 2.4-A resolutions, respectively. The latter three
      compounds were found to stabilize the open conformer. The glycine analogs bind in
      a distinct manner and do not induce the transition to the open state. The complex
      with glycine revealed a third binding mode, reflecting the rather broad substrate
      specificity of AT. These findings identified a role for the alpha-amino group of
      the ligand in stabilizing the open conformer. The kinetic, structural, and
      thermodynamic properties of the mutants ATDeltaM302 and ATDelta11 (lacks 11
      residues of H9) confirmed the key role of Asn300 and suggest that in mammalian
      amidinotransferases, the role of helix H9 is in accelerating amidino transfer by
      an induced-fit mechanism. Helix H9 does not add to the stability of the protein.

PMID- 9915842
TI  - Identification of domains responsible for von Willebrand factor type VI collagen
      interaction mediating platelet adhesion under high flow.
AB  - We have identified type VI collagen (Col VI) as a primary subendothelial
      extracellular matrix component responsible for von Willebrand factor (vWF)
      dependent platelet adhesion and aggregation under high tensile strength. Intact
      tetrameric Col VI was the form of the collagen found to be capable of promoting
      vWF-mediated platelet adhesion/aggregation under this shear condition, whereas
      removal of the predominant portion of the terminal globules by pepsin treatment
      abrogated its activity. The inability of the pepsin-digested Col VI to support
      any platelet interaction at high flow was because of the failure of the A3(vWF)
      domain to bind to this form of collagen, suggesting a stringent requirement of a
      tridimensional conformation or of intactness of its macromolecular structure. In
      contrast, the A1(vWF) domain bound to both intact and pepsin-digested Col VI
      tetramers but, in accordance with the cooperating function of the two vWF
      domains, failed to support platelet adhesion/aggregation under high shear onto
      Col VI by itself. The putative A1(vWF) binding site resided within the A7(VI)
      module (residues 413-613) of the globular amino-terminal portion of the
      alpha3(VI) chain. Soluble recombinant A7(VI) polypeptide strongly perturbed the
      vWF-mediated platelet adhesion to Col VI under high shear rates, without
      affecting the binding of the vWF platelet receptor glycoprotein Ibalpha to its
      cognate ligand A1(vWF). The findings provide evidence for a concerted action of
      the A1(vWF) and A3(vWF) domains in inducing platelet arrest on Col VI. This is
      accomplished via an interaction of the A1(vWF) domain with a site contained in
      the alpha3 chain A7(VI) domain and via a conformation-dependent interaction of
      the A3(vWF) domain with the intact tetrameric collagen. The data further
      emphasize that Col VI microfilaments linking the subendothelial basement membrane
      to the interstitial collagenous network may play a pivotal role in the hemostatic
      process triggered upon damage of the blood vessel wall.

PMID- 9915843
TI  - Unique regulation of immediate early gene and tyrosine hydroxylase expression in
      the odor-deprived mouse olfactory bulb.
AB  - Tyrosine hydroxylase (TH), expressed in a population of periglomerular neurons
      intrinsic to the olfactory bulb, displays dramatic down-regulation in response to
      odor deprivation. To begin to elucidate the importance of immediate early genes
      (IEG) in TH gene regulation, the present study examined expression of IEGs in the
      olfactory bulb in response to odor deprivation. In addition, the composition of
      TH AP-1 and CRE binding complexes was investigated in control and odor-deprived
      mice. Immunocytochemical studies showed that c-Fos, Fos-B, Jun-D, CRE-binding
      protein (CREB), and phosphorylated CREB (pCREB) are colocalized with TH in the
      dopaminergic periglomerular neurons. Unilateral naris closure resulted in down
      regulation of c-Fos and Fos-B, but not Jun-D, CREB, or pCREB, in the glomerular
      layer of the ipsilateral olfactory bulb. Gel shift assays demonstrated a
      significant decrease (32%) in TH AP-1, but not CRE, binding activity in the odor
      deprived bulb. Fos-B was found to be the exclusive member of the Fos family
      present in the TH AP-1 complex. CREB, CRE modulator protein (CREM), Fos-B, and
      Jun-D, but not c-Fos, all contributed to the CRE DNA-protein complex. These
      results indicated that Fos-B, acting through both AP-1 and CRE motifs, may be
      implicated in the regulation of TH expression in the olfactory bulb dopaminergic
      neurons.

PMID- 9915844
TI  - Phosphatidylserine receptors: role of CD36 in binding of anionic phospholipid
      vesicles to monocytic cells.
AB  - Exposure of phosphatidylserine (PtdSer) has been implicated in the recognition
      and phagocytosis of senescent and apoptotic cells, and CD36 has been proposed as
      one receptor protein that recognizes PtdSer and other anionic phospholipids. We
      investigated the binding of phospholipid vesicles to the monocytic leukemia cell
      lines THP-1 and J774A.1 with a flow cytometric assay; vesicles contained 50 mol%
      PtdSer, phosphatidylinositol (PtdIns), or phosphatidylglycerol (PtdGro), with the
      balance being phosphatidylcholine. Specific, high affinity binding was observed
      for vesicles containing PtdSer, PtdIns, or PtdGro. Specificity of the assay was
      confirmed by control experiments with erythrocytes, which showed minimal vesicle
      binding, and with annexin V, which blocked the binding of PtdSer, PtdGro, and
      PtdIns vesicles to the THP-1 cells. However, O-phospho-L-serine (to 1 mM) had no
      effect on the binding of PtdSer vesicles, indicating that high affinity binding
      requires a surface containing multiple phosphoserine groups rather than a single
      molecule. A monoclonal antibody to CD36 blocked up to 60% of the specific binding
      of PtdSer vesicles but had minimal to no effect on the binding of PtdGro or
      PtdIns vesicles. This antibody also selectively inhibited the phagocytosis of
      PtdSer-containing vesicles as measured by fluorescence microscopy, indicating
      that CD36 is functionally significant for phagocytosis of this vesicle type. In
      addition, collagen and thrombospondin, two other putative ligands of CD36, were
      unable to inhibit the binding of PtdSer vesicles. We conclude that CD36 is the
      primary protein responsible for the high affinity binding of PtdSer vesicles to
      these monocyte-like cells. In addition, CD36 appears to be specific for PtdSer
      among anionic phospholipids, and non-phospholipid ligands of CD36 do not share
      binding sites with PtdSer on CD36.

PMID- 9915845
TI  - AKAP350, a multiply spliced protein kinase A-anchoring protein associated with
      centrosomes.
AB  - Protein kinase A-anchoring proteins (AKAPs) localize the second messenger
      response to particular subcellular domains by sequestration of the type II
      protein kinase A. Previously, AKAP120 was identified from a rabbit gastric
      parietal cell cDNA library; however, a monoclonal antibody raised against AKAP120
      labeled a 350-kDa band in Western blots of parietal cell cytosol. Recloning has
      now revealed that AKAP120 is a segment of a larger protein, AKAP350. We have now
      obtained a complete sequence of human gastric AKAP350 as well as partial cDNA
      sequences from human lung and rabbit parietal cells. The genomic region
      containing AKAP350 is found on chromosome 7q21 and is multiply spliced, producing
      at least three distinct AKAP350 isoforms as well as yotiao, a protein associated
      with the N-methyl-D-aspartate receptor. Rabbit parietal cell AKAP350 is missing a
      sequence corresponding to a single exon in the middle of the molecule located
      just after the yotiao homology region. Two carboxyl-terminal splice variants were
      also identified. Both of the major splice variants showed tissue- and cell
      specific expression patterns. Immunofluorescence microscopy demonstrated that
      AKAP350 was associated with centrosomes in many cell types. In polarized Madin
      Darby canine kidney cells, AKAP350 localized asymmetrically to one pole of the
      centrosome, and nocodazole did not alter its localization. During the cell cycle,
      AKAP350 was associated with the centrosomes as well as with the cleavage furrow
      during anaphase and telophase. Several epithelial cell types also demonstrated
      noncentrosomal pools of AKAP350, especially parietal cells, which contained
      multiple cytosolic immunoreactive foci throughout the cells. The localization of
      AKAP350 suggests that it may regulate centrosomal and noncentrosomal cytoskeletal
      systems in many different cell types.

PMID- 9915846
TI  - Side chains that influence fidelity at the polymerase active site of Escherichia
      coli DNA polymerase I (Klenow fragment).
AB  - To investigate the interactions that determine DNA polymerase accuracy, we have
      measured the fidelity of 26 mutants with amino acid substitutions in the
      polymerase domain of a 3'-5'-exonuclease-deficient Klenow fragment. Most of these
      mutant polymerases synthesized DNA with an apparent fidelity similar to that of
      the wild-type control, suggesting that fidelity at the polymerase active site
      depends on highly specific enzyme-substrate interactions and is not easily
      perturbed. In addition to the previously studied Y766A mutator, four novel base
      substitution mutators were identified; they are R668A, R682A, E710A, and N845A.
      Each of these five mutator alleles results from substitution of a highly
      conserved amino acid side chain located on the exposed surface of the polymerase
      cleft near the polymerase active site. Analysis of base substitution errors at
      four template positions indicated that each of the five mutator polymerases has
      its own characteristic error specificity, suggesting that the Arg-668, Arg-682,
      Glu-710, Tyr-766, and Asn-845 side chains may contribute to polymerase fidelity
      in a variety of different ways. We separated the contributions of the nucleotide
      insertion and mismatch extension steps by using a novel fidelity assay that
      scores base substitution errors during synthesis to fill a single nucleotide gap
      (and hence does not require mismatch extension) and by measuring the rates of
      polymerase-catalyzed mismatch extension reactions. The R682A, E710A, Y766A, and
      N845A mutations cause decreased fidelity at the nucleotide insertion step,
      whereas R668A results in lower fidelity in both nucleotide insertion and mismatch
      extension. Relative to wild type, several Klenow fragment mutants showed
      substantially more discrimination against extension of a T.G mismatch under the
      conditions of the fidelity assay, providing one explanation for the anti-mutator
      phenotypes of mutants such as R754A and Q849A.

PMID- 9915847
TI  - Characterization of the human endothelial nitric-oxide synthase promoter.
AB  - Understanding transcription initiation of the endothelial nitric-oxide synthase
      (eNOS) gene appears pivotal to gaining a comprehensive view of NO biology in the
      blood vessel wall. The present study therefore focused upon a detailed dissection
      of the functionally important cis-DNA elements and the multiprotein complexes
      implicated in the cooperative control of constitutive expression of the human
      eNOS gene in vascular endothelium. Two tightly clustered cis-regulatory regions
      were identified in the proximal enhancer of the TATA-less eNOS promoter using
      deletion analysis and linker-scanning mutagenesis: positive regulatory domains I
      (-104/-95 relative to transcription initiation) and II (-144/-115). Analysis of
      trans-factor binding and functional expression studies revealed a surprising
      degree of cooperativity and complexity. The nucleoprotein complexes that form
      upon these regions in endothelial cells contained Ets family members, Sp1,
      variants of Sp3, MAZ, and YY1. Functional domain studies in Drosophila Schneider
      cells and endothelial cells revealed examples of positive and negative protein
      protein cooperativity involving Sp1, variants of Sp3, Ets-1, Elf-1, and MAZ.
      Therefore, multiprotein complexes are formed on the activator recognition sites
      within this 50-base pair region of the human eNOS promoter in vascular
      endothelium.

PMID- 9915848
TI  - Differential role of insulin receptor substrate (IRS)-1 and IRS-2 in L6 skeletal
      muscle cells expressing the Arg1152 --> Gln insulin receptor.
AB  - In L6 muscle cells expressing the Arg1152 --> Gln insulin receptor (Mut), basal
      tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was increased by
      35% compared with wild-type cells (WT). Upon exposure to insulin, IRS-1
      phosphorylation increased by 12-fold in both the Mut and WT cells. IRS-2 was
      constitutively phosphorylated in Mut cells and not further phosphorylated by
      insulin. The maximal phosphorylation of IRS-2 in basal Mut cells was paralleled
      by a 4-fold increased binding of the kinase regulatory loop binding domain of IRS
      2 to the Arg1152 --> Gln receptor. Grb2 and phosphatidylinositol 3-kinase
      association to IRS-1 and IRS-2 reflected the phosphorylation levels of the two
      IRSs. Mitogen-activated protein kinase activation and [3H]thymidine incorporation
      closely correlated with IRS-1 phosphorylation in Mut and WT cells, while glycogen
      synthesis and synthase activity correlated with IRS-2 phosphorylation. The
      Arg1152 --> Gln mutant did not signal Shc phosphorylation or Shc-Grb2 association
      in intact L6 cells, while binding Shc in a yeast two-hybrid system and
      phosphorylating Shc in vitro. Thus, IRS-2 appears to mediate insulin regulation
      of glucose storage in Mut cells, while insulin-stimulated mitogenesis correlates
      with the activation of the IRS-1/mitogen-activated protein kinase pathway in
      these cells. IRS-1 and Shc-mediated mitogenesis may be redundant in muscle cells.

PMID- 9915849
TI  - Functional coupling between various phospholipase A2s and cyclooxygenases in
      immediate and delayed prostanoid biosynthetic pathways.
AB  - Several distinct phospholipase A2s (PLA2s) and two cyclooxygenases (COXs) were
      transfected, alone or in combination, into human embryonic kidney 293 cells, and
      their functional coupling during immediate and delayed prostaglandin (PG)
      biosynthetic responses was reconstituted. Signaling PLA2s, i.e. cytosolic PLA2
      (cPLA2) (type IV) and two secretory PLA2s (sPLA2), types IIA (sPLA2-IIA) and V
      (sPLA2-V), promoted arachidonic acid (AA) release from their respective
      transfectants after stimulation with calcium ionophore or, when bradykinin
      receptor was cotransfected, with bradykinin, which evoked the immediate response,
      and interleukin-1 plus serum, which induced the delayed response. Experiments on
      cells transfected with either COX alone revealed subtle differences between the
      PG-biosynthetic properties of the two isozymes in that COX-1 and COX-2 were
      favored over the other in the presence of high and low exogenous AA
      concentrations, respectively. Moreover, COX-2, but not COX-1, could turn on
      endogenous AA release, which was inhibited by a cPLA2 inhibitor. When PLA2 and
      COX were coexpressed, AA released by cPLA2, sPLA2-IIA and sPLA2-V was converted
      to PGE2 by both COX-1 and COX-2 during the immediate response and predominantly
      by COX-2 during the delayed response. Ca2+-independent PLA2 (iPLA2) (type VI),
      which plays a crucial role in phospholipid remodeling, failed to couple with COX
      2 during the delayed response, whereas it was linked to ionophore-induced
      immediate PGE2 generation via COX-1 in marked preference to COX-2. Finally,
      coculture of PLA2 and COX transfectants revealed that extracellular sPLA2s-IIA
      and -V, but neither intracellular cPLA2 nor iPLA2, augmented PGE2 generation by
      neighboring COX-expressing cells, implying that the heparin-binding sPLA2s play a
      particular role as paracrine amplifiers of the PG-biosynthetic response signal
      from one cell to another.

PMID- 9915850
TI  - CD80 and CD86 are not equivalent in their ability to induce the tyrosine
      phosphorylation of CD28.
AB  - Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is
      thought to skew the immune response toward Th1 or Th2 differentiation. We have
      examined early signal transduction pathways recruited following T cell
      stimulation with either CD80 or CD86. Purified human peripheral T cells or Jurkat
      T cells were stimulated with Chinese hamster ovary (CHO) cells expressing either
      human CD80 (CHO-CD80) or human CD86 (CHO-CD86) or with anti-CD28 monoclonal
      antibody (mAb). In the presence of phorbol 12-myristate 13-acetate, both CHO-CD80
      and CHO-CD86, like anti-CD28 mAb, were capable of stimulating cytokine production
      from both human peripheral T cells and Jurkat T cells. Both CHO-CD80 and CHO
      CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent
      transcriptional activation. Several intracellular signaling proteins, such as CBL
      and VAV, were phosphorylated on tyrosine in response to CD80, CD86, and anti-CD28
      mAb. Surprisingly, although stimulation of Jurkat T cells with either CHO-CD80 or
      anti-CD28 mAb resulted in robust tyrosine phosphorylation of CD28 itself,
      ligation with CHO-CD86 was unable to induce detectable CD28 tyrosyl
      phosphorylation over a range of stimulation conditions. In addition, the
      association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine
      phosphorylation of phospholipase Cgamma were seen after anti-CD28 mAb and CHO
      CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation. Thus,
      ligation of CD28 with either CD80 or CD86 leads to shared early signal
      transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT
      mediated transcriptional activation, and to the costimulation of interleukin-2
      and granulocyte-macrophage colony-stimulating factor production. However, CD80
      and CD86 also induce distinct signal transduction pathways including the tyrosine
      phosphorylation of CD28 and phospholipase Cgamma1 and the SH2-dependent
      association of phosphoinositide 3-kinase with CD28. These quantitative, if not
      qualitative, differences between signaling initiated by these two ligands for
      CD28 may contribute to functional differences (e.g. Th1 or Th2 differentiation)
      in T cell responses.

PMID- 9915851
TI  - Purification of a 38-kDa protein from rabbit reticulocyte lysate which promotes
      protein renaturation by heat shock protein 70 and its identification as delta
      aminolevulinic acid dehydratase and as a putative DnaJ protein.
AB  - We reported recently that a rabbit reticulocyte 66-kDa protein (termed RF-hsp 70
      by our laboratory and p60 and hop by others) functions as a hsp 70 recycling
      protein and markedly enhances the renaturation of luciferase by hsp 70 (Gross,
      M., and Hessefort, S. (1996) J. Biol. Chem. 271, 16833-16841). In this report, we
      confirm that the ability of RF-hsp 70 to promote the conversion of hsp 70. ADP to
      hsp 70.ATP, thus enhancing the protein folding activity of hsp 70, is caused by
      the purified 66-kDa protein and not by a trace DnaJ/hsp 40 protein contaminant.
      To determine the relationship between RF-hsp 70 and the DnaJ/hsp 40 heat shock
      protein family, which also enhances protein renaturation by hsp 70, we purified a
      38-kDa protein from rabbit reticulocyte lysate based upon its ability to
      stimulate renaturation of luciferase by hsp 70. Partial amino acid sequencing of
      this 38-kDa protein has indicated, unexpectedly, that it is the enzyme delta
      aminolevulinic acid dehydratase (ALA-D) and that it does not contain detectable
      sequences corresponding to the DnaJ/hsp 40 protein family. In addition,
      immunoblot analysis with a polyclonal antibody made to HeLa cell hsp 40 (from
      StressGen) confirms that our purified ALA-D contains no hsp 40, although hsp 40
      is present in relatively crude rabbit reticulocyte protein fractions. Rabbit
      reticulocyte ALA-D is about as active in converting delta-aminolevulinic acid to
      porphobilinogen and as Zn2+-dependent as ALA-D purified from other sources.
      Rabbit reticulocyte ALA-D stimulates the renaturation of luciferase by hsp 70 up
      to 10-fold at concentrations that are the same as or less than that of hsp 70,
      and it has no renaturation activity in the absence of hsp 70. The renaturation
      effect of ALA-D is additive with that of RF-hsp 70 at limiting or saturating
      concentrations of each, and, unlike RF-hsp 70, ALA-D does not promote the
      dissociation of hsp 70.ADP in the presence of ATP. The renaturation-enhancing
      effect of ALA-D may be caused by a region near its carboxyl terminus which has
      sequence homology to the highly conserved domain of the DnaJ protein family,
      which is similar to the sequence homology between this domain and a carboxyl
      terminal region in auxilin, a DnaJ-like protein that requires this region for its
      hsp 70-dependent function (Ungewickell, E., Ungewickell, H., Holstein, S. E. H.,
      Lindner, R., Prasad, K., Barouch, W., Martin, B., Greene, L. E., and Eisenberg,
      E. (1995) Nature 378, 632-635).

PMID- 9915852
TI  - Sensitivity of Drosophila heat shock transcription factor to low pH.
AB  - The heat shock transcription factor (HSF) mediates the induction of heat shock
      gene expression. The activation of HSF involves heat shock-induced trimerization,
      binding to its cognate DNA sites, and the acquisition of transcriptional
      competence. In this study, the oligomeric properties of Drosophila HSF were
      analyzed by equilibrium analytical ultracentrifugation and gel filtration
      chromatography. Previous findings showed that trimerization of purified
      Drosophila HSF was directly sensitive to heat and oxidation (1). Here we report
      that low pH, in the physiological range, also directly induces HSF trimerization
      and DNA binding in vitro. Furthermore, the induction of HSF trimerization by low
      pH is synergistic with the actions of heat and oxidation. Since heat or chemical
      stress leads to a moderate decrease of intracellular pH, we suggest that
      intracellular acidification may contribute to activating the heat shock response
      in vivo.

PMID- 9915853
TI  - A leucine-based determinant in the epidermal growth factor receptor juxtamembrane
      domain is required for the efficient transport of ligand-receptor complexes to
      lysosomes.
AB  - Ligand binding causes the epidermal growth factor (EGF) receptor to undergo
      accelerated internalization with eventual degradation in lysosomes. The goal of
      this study was to investigate the molecular basis of endocytic sorting, focussing
      on post-internalization events. We have identified a sequence located between
      amino acid residues 675 and 697, encompassing a dileucine motif at residues 679
      and 680, that enhances endosome-to-lysosome transport when conformational
      restraints in the EGF receptor carboxyl terminus are removed by truncation. The
      same dileucine motif is also necessary for efficient lysosomal transport of
      ligand-occupied full-length EGF receptors. A L679A,L680A substitution diminished
      the degradation of occupied full-length EGF receptors without affecting
      internalization but had a significant effect on recycling. Rapid recycling of
      mutant receptors resulted in reduced intracellular retention of occupied EGF
      receptors and delayed down-regulation of cell surface receptors. We propose that
      the L679A,L680A substitution acts primarily to impair transport of ligand
      receptor complexes through an early endosomal compartment, diverting occupied
      receptors to a recycling compartment at the expense of incorporation into
      lysosome transport vesicles. We also found that mutant receptors with truncations
      at the distal half of tyrosine kinase domain (residues 809-957) were not
      efficiently delivered to the cell surface but were destroyed in an endoplasmic
      reticulum-associated degradative pathway.

PMID- 9915854
TI  - Pituitary tumor-transforming gene protein associates with ribosomal protein S10
      and a novel human homologue of DnaJ in testicular cells.
AB  - Pituitary tumor-transforming gene (PTTG) is a recently characterized proto
      oncogene that is expressed specifically in adult testis. In this study, we have
      used in situ hybridization and developmental Northern blot assays to demonstrate
      that PTTG mRNA is expressed stage-specifically in spermatocytes and spermatids
      during rat spermatogenic cycle. We have used the yeast two-hybrid system to
      identify proteins that interact with PTTG in testicular cells. Two positive
      clones were characterized. One of the clones is the ribosomal protein S10, the
      other encodes a novel human DnaJ homologue designated HSJ2. Northern blot
      analysis showed that testis contains higher levels of HSJ2 mRNA than other
      tissues examined, and the expression pattern of HSJ2 mRNA in postnatal rat testis
      is similar to PTTG. S10 mRNA levels do not vary remarkably among different
      tissues and remains unchanged during testicular germ cell differentiation. In
      vitro binding assays demonstrated that both S10 and HSJ2 bind to PTTG
      specifically and that PTTG can be co-immunoprecipitated with S10 and HSJ2 from
      transfected cells. Moreover, the binding sites for both proteins were located
      within the C-terminal 75 amino acids of the PTTG protein. These results suggest
      that PTTG may play a role in spermatogenesis.

PMID- 9915855
TI  - A common binding site on the microsomal triglyceride transfer protein for
      apolipoprotein B and protein disulfide isomerase.
AB  - The assembly of triglyceride-rich lipoproteins requires the formation in the
      endoplasmic reticulum of a complex between apolipoprotein B (apoB), a microsomal
      triglyceride transfer protein (MTP), and protein disulfide isomerase (PDI). In
      the MTP complex, the amino-terminal region of MTP (residues 22-303) interacts
      with the amino-terminal region of apoB (residues 1-264). Here, we report the
      identification and characterization of a site on apoB between residues 512 and
      721, which interacts with residues 517-603 of MTP. PDI binds in close proximity
      to this apoB binding site on MTP. The proximity of these binding sites on MTP for
      PDI and amino acids 512-721 of apoB was evident from studies carried out in a
      yeast two-hybrid system and by co-immunoprecipitation. The expression of PDI with
      MTP and apoB16 (residues 1-721) in the baculovirus expression system reduced the
      amount of MTP co-immunoprecipitated with apoB by 73%. The interaction of residues
      512-721 of apoB with MTP facilitates lipoprotein production. Mutations of apoB
      that markedly reduced this interaction also reduced the level of apoB-containing
      lipoprotein secretion.

PMID- 9915856
TI  - The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP)
      inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP).
      Colocalization of KPI/APP and PTP in secretory vesicles.
AB  - Proteolytic processing of proenkephalin and proneuropeptides is required for the
      production of active neurotransmitters and peptide hormones. Variations in the
      extent of proenkephalin processing in vivo suggest involvement of endogenous
      protease inhibitors. This study demonstrates that "protease nexin 2 (PN2)," the
      secreted form of the kunitz protease inhibitor (KPI) of the amyloid precursor
      protein (APP), potently inhibited the proenkephalin processing enzyme known as
      prohormone thiol protease (PTP), with a Ki,app of 400 nM. Moreover, PTP and PN2
      formed SDS-stable complexes that are typical of kunitz protease inhibitor
      interactions with target proteases. In vivo, KPI/APP (120 kDa), as well as a
      truncated form of KPI/APP that resembles PN2 in apparent molecular mass (110
      kDa), were colocalized with PTP and (Met)enkephalin in secretory vesicles of
      adrenal medulla (chromaffin granules). KPI/APP (110-120 kDa) was also detected in
      pituitary secretory vesicles that contain PTP. In chromaffin cells, calcium
      dependent secretion of KPI/APP with PTP and (Met)enkephalin demonstrated the
      colocalization of these components in functional secretory vesicles. These
      results suggest a role for KPI/APP inhibition of PTP in regulated secretory
      vesicles. In addition, these results are the first to identify an endogenous
      protease target of KPI/APP, which is developmentally regulated in aging and
      Alzheimer's disease.

PMID- 9915857
TI  - Deletion mapping of N-terminal domains of surfactant protein A. The N-terminal
      segment is required for phospholipid aggregation and specific inhibition of
      surfactant secretion.
AB  - The objective of the current study was to examine the functional importance of
      the N-terminal domains of surfactant protein A (SP-A) including the N-terminal
      segment from Asn1 to Ala7 (denoted domain 1), the N-terminal portion of the
      collagen domain from Gly8 to Gly44 (domain 2), and the C-terminal portion of the
      collagen-like domain from Gly45 to Pro80 (domain 3). Wild type recombinant SP-A
      (SP-Ahyp; where hyp indicates hydroxyproline-deficient) and truncated mutant (TM)
      SP-As containing deletions of domain(s) 1 (TM1), 2 (TM2), 1 and 2 (TM1-2), and 1,
      2, and 3 (TM1-2-3) were synthesized in insect cells and purified by mannose
      Sepharose affinity chromatography. N-terminal disulfide-dependent dimerization
      was preserved at near wild type levels in the TM1-2 (at Cys-1) and TM2 proteins
      (at Cys-1 and Cys6), and to a lesser extent in TM1 (at Cys-1), but not in TM1-2
      3. Cross-linking analyses demonstrated that the neck + CRD was sufficient for
      assembly of monomers into noncovalent trimers and that the N-terminal segment was
      required for the association of trimers to form higher oligomers. All TM proteins
      except TM1-2-3 bound to phospholipid, but only the N-terminal segment containing
      TM proteins aggregated phospholipid vesicles. The TM1, TM1-2, and TM2 but not the
      TM1-2-3 inhibited the secretion of surfactant from type II cells as effectively
      as SP-Ahyp, but the inhibitory activity of each mutant was blocked by excess
      alpha-methylmannoside and therefore nonspecific. TM1 and TM1-2-3 did not enhance
      the uptake of phospholipids by isolated type II cells, but the TM1-2 and TM2 had
      activities that were 72 and 83% of SP-Ahyp, respectively. We conclude the
      following for SP-A: 1) trimerization does not require the collagen-like region or
      interchain disulfide linkage; 2) the N-terminal portion of the collagen-like
      domain is required for specific inhibition of surfactant secretion but not for
      binding to liposomes or for enhanced uptake of phospholipids into type II cells;
      3) N-terminal interchain disulfide linkage can functionally replace the N
      terminal segment for lipid binding, receptor binding, and enhancement of lipid
      uptake; 4) the N-terminal segment is required for the association of trimeric
      subunits into higher oligomers, for phospholipid aggregation, and for specific
      inhibition of surfactant secretion and cannot be functionally replaced by
      disulfide linkage alone for these activities.

PMID- 9915858
TI  - Direct association with thioredoxin allows redox regulation of glucocorticoid
      receptor function.
AB  - The glucocorticoid receptor (GR) is considered to belong to a class of
      transcription factors, the functions of which are exposed to redox regulation. We
      have recently demonstrated that thioredoxin (TRX), a cellular reducing catalyst,
      plays an important role in restoration of GR function in vivo under oxidative
      conditions. Although both the ligand binding domain and other domains of the GR
      have been suggested to be modulated by TRX, the molecular mechanism of the
      interaction is largely unknown. In the present study, we hypothesized that the
      DNA binding domain (DBD) of the GR, which is highly conserved among the nuclear
      receptors, is also responsible for communication with TRX in vivo. Mammalian two
      hybrid assay and glutathione S-transferase pull-down assay revealed the direct
      association between TRX and the GR DBD. Moreover, analysis of subcellular
      localization of TRX and the chimeric protein harboring herpes simplex viral
      protein 16 transactivation domain and the GR DBD indicated that the interaction
      might take place in the nucleus under oxidative conditions. Together these
      observations indicate that TRX, via a direct association with the conserved DBD
      motif, may represent a key mediator operating in interplay between cellular redox
      signaling and nuclear receptor-mediated signal transduction.

PMID- 9915860
TI  - Sp1 and egr-1 have opposing effects on the regulation of the rat Pgp2/mdr1b gene.
AB  - The promoter of the rat pgp2/mdr1b gene has a GC-rich region (pgp2GC) that is
      highly conserved in mdr genes and contains an consensus Sp1 site. Sp1's role in
      transactivation of the pgp2/mdr1b promoter was tested in Drosophila Schneider
      cells. The pgp2/mdr1b promoter was strongly activated by co-transfected wild type
      Sp1 but not mutant Sp1 and mutation of the Sp1 site abrogated Sp1-dependent
      transactivation. In gel shift assays, the same mutations abolished Sp1-DNA
      complex formation. Moreover, basal activity of the pgp2/mdr1b Sp1 mutant promoter
      was dramatically lower. Enforced ectopic overexpression of Sp1 in H35 rat
      hepatoma cells revealed that cell lines overexpressing Sp1 had increased
      endogenous pgp2/mdr1b mRNA, demonstrating that Sp1 activates the endogenous
      pgp2/mdr1b gene. Pgp2GC oligonucleotide also bound Egr-1 in gel shift assays and
      Egr-1 competitively displaced bound Sp1. In transient transfections of H35 cells
      (and human LS180 and HepG2 cells) Egr-1 potently and specifically suppressed
      pgp2/mdr1b promoter activity and mutations in the Egr-1 site decreased Egr-1
      binding and correlated with pgp2/mdr1b up-regulation. Ectopic overexpression of
      Egr-1 in H35 cells decreased Pgp expression and selectively increased vinblastine
      sensitivity. In conclusion, Sp1 positively regulates while Egr-1 negatively
      regulates the rat pgp2/mdr1b gene. Moreover, competitive interactions between Sp1
      and Egr-1 in all likelihood determine the constitutive expression of the
      pgp2/mdr1b gene in H35 cells.

PMID- 9915859
TI  - Cascades of mammalian caspase activation in the yeast Saccharomyces cerevisiae.
AB  - Caspases (aspartate-specific cysteine proteases) play a critical role in the
      execution of the mammalian apoptotic program. To address the regulation of human
      caspase activation, we used the yeast Saccharomyces cerevisiae, which is devoid
      of endogenous caspases. The apical procaspases, -8beta and -10, were efficiently
      processed and activated in yeast. Although protease activity, per se, was
      insufficient to drive cell death, caspase-10 activity had little effect on cell
      viability, whereas expression of caspase-8beta was cytotoxic. This lethal
      phenotype was abrogated by co-expression of the pan-caspase inhibitor,
      baculovirus p35, and by mutation of the active site cysteine of procaspase-8beta.
      In contrast, autoactivation of the executioner caspase-3 and -6 zymogens was not
      detected. Procaspase-3 activation required co-expression of procaspase-8 or -10.
      Surprisingly, activation of procaspase-6 required proteolytic activities other
      than caspase-8, -10, or -3. Caspase-8beta or -10 activity was insufficient to
      catalyze the maturation of procaspase-6. Moreover, a constitutively active
      caspase-3, although cytotoxic in its own right, was unable to induce the
      processing of wild-type procaspase-6 and vice versa. These results distinguish
      sequential modes of activation for different caspases in vivo and establish a
      yeast model system to examine the regulation of caspase cascades. Moreover, the
      distinct terminal phenotypes induced by various caspases attest to differences in
      the cellular targets of these apoptotic proteases, which may be defined using
      this system.

PMID- 9915861
TI  - The human KDR/flk-1 gene contains a functional initiator element that is bound
      and transactivated by TFII-I.
AB  - KDR/flk-1, the receptor for vascular endothelial growth factor, is required for
      normal vascular development. KDR/flk-1 is a TATA-less gene, containing four
      upstream Sp1 sites and a single transcription start site, although analysis of
      the start site sequence discloses only weak similarities with the consensus
      initiator element (Inr) sequence. In vitro transcription assays, however,
      demonstrate that the region from -10 to +10 relative to the start site contains
      Inr activity that is orientation- and position-dependent, and mutagenesis of the
      KDR/flk-1 Inr reduces promoter activity to 28% of the wild-type promoter in
      transient transfection assays. Gel shift assays confirm that nuclear proteins
      specifically bind the Inr, and competition experiments demonstrate that TFII-I, a
      multifunctional Inr-binding nuclear protein, is a component of these DNA-protein
      complexes. TFII-I transactivates the wild-type KDR/flk-1 promoter, but not a
      promoter containing a mutated Inr, in transient transfection assays.
      Immunodepletion of TFII-I from nuclear extracts prior to in vitro transcription
      assays abolishes transcription from the KDR/flk-1 Inr, an effect that can be
      rescued by adding back purified TFII-I, reflecting the importance of TFII-I in
      KDR/flk-1 Inr activity. These experiments demonstrate that the KDR/flk-1 gene
      contains a functional Inr that is bound by TFII-I and that both the functional
      Inr and TFII-I activity are essential for transcription.

PMID- 9915862
TI  - Molecular cloning and expression of a novel beta-1, 6-N
      acetylglucosaminyltransferase that forms core 2, core 4, and I branches.
AB  - Mucin-type O-glycans are classified according to their core structures. Among
      them, cores 2 and 4 are important for having N-acetyllactosamine side chains,
      which can be further modified to express various functional oligosaccharides.
      Previously, we discovered by cloning cDNAs that the core 2 branching enzyme,
      termed core 2 beta-1,6-N-acetylglucosaminyltransferase-leukocyte type (C2GnT-L),
      is highly homologous to the I branching beta-1, 6-N-acetylglucosaminyltransferase
      (IGnT) (Bierhuizen, M. F. A., Mattei, M.-G., and Fukuda, M. (1993) Genes Dev. 7,
      468-478). Using these homologous sequences as probes, we identified an expressed
      sequence tag in dbEST, which has significant homology to C2GnT-L and IGnT. This
      approach, together with 5'and 3' rapid amplification of cDNA ends, yielded a
      human cDNA that encompasses a whole coding region of an enzyme, termed C2GnT
      mucin type (C2GnT-M). C2GnT-M has 48.2 and 33.8% identity with C2GnT-L and IGnT
      at the amino acid levels. The expression of C2GnT-M cDNA directed the expression
      of core 2 branched oligosaccharides and I antigen on the cell surface. Moreover,
      a soluble chimeric C2GnT-M had core 4 branching activity in addition to core 2
      and I branching activities. A soluble chimeric C2GnT-L, in contrast, almost
      exclusively contains core 2 branching activity. Northern blot analysis
      demonstrated that the C2GnT-M transcripts are heavily expressed in colon, small
      intestine, trachea, and stomach, where mucin is produced. In contrast, the
      transcripts of C2GnT-L were more widely detected, including the lymph node and
      bone marrow. These results indicate that the newly cloned C2GnT-M plays a
      critical role in O-glycan synthesis in mucins and might have distinctly different
      roles in oligosaccharide ligand formation compared with C2GnT-L.

PMID- 9915863
TI  - Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant
      double-negative lpr and gld T cells.
AB  - We previously identified a Fas ligand regulatory element (FLRE) in the Fas ligand
      (fasL) promoter that binds Egr family proteins and demonstrated that Egr-3
      (PILOT) but not Egr-1 (NGFI-A, Krox-24, Tis-8, and Zif-268) induces transcription
      of fasL. The aberrant CD4(-)CD8(-) T cells from lpr/lpr and gld/gld mice, which
      have mutations in the genes encoding Fas and FasL, respectively, have an
      activated phenotype and constitutively express high levels of fasL mRNA,
      prompting us to ask what role if any the FLRE and Egr family proteins have in
      this aberrant expression of fasL. Unstimulated MRL-lpr/lpr and C3H-gld/gld CD4(
      )CD8(-) T cells constitutively contained high levels of two proteins that bound
      to the FLRE. Supershift analysis revealed these proteins to be Egr-1 and Egr-2
      (Krox-20); Egr-3 was not detected. Activation of normal lymph node cells resulted
      in increased expression of Egr-1, -2, and -3. As with egr-3, expression of egr-2
      was blocked by cyclosporin A. Although overexpressed Egr-1 was ineffective,
      overexpressed Egr-2 was as potent as Egr-3 in inducing fasL promoter-dependent
      reporter constructs in T cell hybridomas and HeLa cells, and both up-regulated
      endogenous fasL mRNA in HeLa cells. FasL-dependent reporter constructs in MRL
      lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells were constitutively active, and this
      activity was largely prevented by mutation of the critical Egr family binding
      element. Thus, Egr-2, in addition to Egr-3, regulates FasL expression in
      activated normal T cells, and Egr-2 is likely to play a direct role in aberrant
      fasL up-regulation in lpr/lpr and gld/gld CD4(-)CD8(-) T cells.

PMID- 9915864
TI  - Regulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during
      wound healing.
AB  - Endothelin-1 (ET-1) is involved in the pathogenesis of a number of diseases,
      including wound healing. In cirrhosis, the wounding response of the liver,
      circulating ET-1 levels are elevated; moreover, ET-1 has potent effects on
      hepatic stellate cells, the key effectors of cirrhosis. In this study, we have
      examined the regulatory role of ECE-1, a critical enzyme involved in ET-1
      synthesis, in the two major cellular sources of hepatic ET-1. ET-1 release from
      normal hepatic endothelial cells was 25-fold higher than that from normal
      stellate cells. However, after liver injury, ET-1 release was increased in
      stellate cells but markedly decreased in endothelial cells. The two major
      isoforms of ECE-1, ECE-1alpha/1beta, made up 80% and 20%, respectively, of total
      ECE-1 in both stellate and endothelial cells. Following liver injury, ECE-1alpha
      mRNA was decreased by 44.2% in stellate cells, and by 16.1% in endothelial cells.
      ECE-1beta mRNA expression remained unchanged after injury. In contrast to ECE-1
      mRNA, ECE-1 protein expression was increased by 43.9% in stellate cells but
      decreased in endothelial cells, while relative ECE-1 enzymatic activity was
      unchanged. In mRNA stability experiments, the half-life of ECE-1alpha mRNA in
      normal stellate cells was 13 h compared with 38 h in cells from injured livers.
      Thus, during hepatic wound healing, differential regulation of ECE-1 mRNA and
      protein appears to be critical in controlling ET-1 production.

PMID- 9915866
TI  - The role of calcium on the activity of ERcalcistorin/protein-disulfide isomerase
      and the significance of the C-terminal and its calcium binding. A comparison with
      mammalian protein-disulfide isomerase.
AB  - ERcalcistorin/protein-disulfide isomerase (ECaSt/PDI) shows a 55% identity with
      mammalian protein-disulfide isomerase (PDI) (Lucero, H. A., Lebeche, D., and
      Kaminer, B. (1994) J. Biol. Chem. 269, 23112-23119) is a high capacity low
      affinity Ca2+-binding protein and behaves as a Ca2+ storage protein in the ER of
      a living cell (Lucero, H. A., Lebeche, D., and Kaminer, B. (1998) J. Biol. Chem.
      273, 9857-9863). Here we show that recombinant ECaSt/PDI bound 26 mol of Ca2+/mol
      and a C-terminal truncated mutant bound 14 mol of Ca2+/mol, both with a Kd of 2.8
      mM in 50 mM KCl and 5.2 mM in 150 mM KCl. The percentage reduction in Ca2+
      binding in the mutant corresponded with the percentage reduction of deleted pairs
      of acidic residues, postulated low affinity Ca2+-binding sites. 5 mM Ca2+
      moderately increased the PDI activity of both ECaSt/PDI and the C-terminal
      truncated mutant on reduced RNase and insulin. Surprisingly, ECaSt/PDI in the
      absence of Ca2+ prevented the spontaneous reactivation of reduced bovine
      pancreatic trypsin inhibitor. In the presence of 1-5 mM Ca2+ (or 10 microM
      polylysine) ECaSt/PDI augmented the bovine pancreatic trypsin inhibitor
      reactivation rate. In contrast, the C-terminal truncated ECaSt/PDI augmented
      rBPTI reactivation in the absence of Ca2+ and 1-5 mM Ca2+ further accelerated the
      reactivation rate, responses similar to those obtained with mammalian PDI.

PMID- 9915865
TI  - Cholesterol efflux-mediated signal transduction in mammalian sperm. beta
      cyclodextrins initiate transmembrane signaling leading to an increase in protein
      tyrosine phosphorylation and capacitation.
AB  - Sperm capacitation in vitro is highly correlated with an increase in protein
      tyrosine phosphorylation that is regulated by cAMP through a unique mode of
      signal transduction cross-talk. The activation of this signaling pathway, as well
      as capacitation, requires bovine serum albumin (BSA) in the incubation medium.
      BSA is hypothesized to modulate capacitation through its ability to remove
      cholesterol from the sperm plasma membrane. Here we demonstrate that the
      cholesterol-binding heptasaccharides, methyl-beta-cyclodextrin and OH-propyl-beta
      cyclodextrin, promote the release of cholesterol from the mouse sperm plasma
      membrane in media devoid of BSA. Both of these beta-cyclodextrins were also
      demonstrated to increase protein tyrosine phosphorylation in the absence of BSA
      in both mouse and bull sperm, and the patterns of phosphorylation were similar to
      those induced by media containing BSA. The potency of the different beta
      cyclodextrins to increase protein tyrosine phosphorylation in sperm was
      correlated with their cholesterol binding efficiencies, and preincubation of the
      beta-cyclodextrins with cholesterol-SO4- to saturate their cholesterol-binding
      sites blocked the ability of these compounds to stimulate protein tyrosine
      phosphorylation. The beta-cyclodextrin effect on protein tyrosine phosphorylation
      was both NaHCO3 and protein kinase A-dependent. The beta-cyclodextrins were also
      able to capacitate mouse sperm in the absence of BSA, as measured by the ability
      of the zona pellucida to induce the acrosome reaction and by successful
      fertilization in vitro. In summary, beta-cyclodextrins can completely replace BSA
      in media to support signal transduction leading to capacitation. These data
      further support the coupling of cholesterol efflux to the activation of membrane
      and transmembrane signaling events leading to the activation of a unique
      signaling pathway involving the cross-talk between cAMP and tyrosine kinase
      second messenger systems, thus defining a new mode of cellular signal
      transduction initiated by cholesterol release.

PMID- 9915867
TI  - beta-Carotene, carotenoids and the prevention of coronary heart disease.
AB  - The importance of low density lipoprotein (LDL) oxidation to the atherosclerotic
      process has led to the examination of beta-carotene as a possible preventive
      agent. Several epidemiologic studies show an inverse association between
      serum/adipose beta-carotene levels and coronary heart disease risk. Randomized
      clinical trials, however, have not shown any benefit, and perhaps even an adverse
      effect, of beta-carotene supplementation. A number of possible confounding
      factors may explain the inconsistency between the trials and epidemiologic
      evidence. Other carotenoids that are correlated with beta-carotene both in the
      diet and in the blood might be important factors, as might other plant-derived
      compounds. Alternatively, low serum carotenoid levels may reflect either
      increased lipoprotein density or the presence of inflammation, both factors
      emerging as important novel risk factors for coronary heart disease. Whereas the
      trial results support no preventive role for beta-carotene, the epidemiologic
      evidence does generally support the idea that a diet rich in high carotenoid
      foods is associated with a reduced risk of heart disease.

PMID- 9915868
TI  - Nutritional aspects of calcium absorption.
AB  - The amount of calcium absorbed in the intestine depends on habitual calcium
      intake. When intake is low, active transcellular calcium transport in the
      duodenum is upregulated and a larger proportion of calcium is absorbed by the
      active process than by the passive paracellular process that prevails in the
      jejunum and ileum. Bioavailability of the calcium source-digestibility and
      solubilization-plays a role under conditions of low calcium intake but is
      relatively unimportant when calcium intakes are high (e.g. >800 mg/d in people).
      Vitamin D intake is a second factor, as active calcium transport is directly and
      proportionally dependent on the presence in the intestinal cell of calbindin D9k,
      the biosynthesis of which is totally vitamin D dependent. Passive absorption in
      jejunum and ileum is the major absorptive process when calcium intake is adequate
      or high. Passive calcium absorption is a complicated function of solubility in
      the distal small intestine, the length of sojourn of the chyme in a given
      intestinal segment, and the rate of paracellular diffusion from lumen to lymph
      and blood. Calcium that reaches the large intestine undergoes absorption there by
      both active and passive processes. Probably no more than 10% of total calcium
      absorption takes place in the large intestine, whether calcium intake is low or
      high. Calcium absorption by the large bowel can assume nutritional importance
      under conditions of significant small bowel resection.

PMID- 9915869
TI  - Harold martin scott (1901-1991) 

PMID- 9915870
TI  - Hydrogenated fat high in trans monoenes with an adequate level of linoleic acid
      has no effect on prostaglandin synthesis in rats.
AB  - Our study was designed to determine whether hydrogenated fat high in trans
      monoenes concentration affected prostaglandin synthesis. Corn oil (CO), butter
      (B), hydrogenated vegetable oil (HF) and coating fat (CF) were used in this
      study. These fats were fed to rats for 10 wk at 10 g/100 g diet. The phospholipid
      (PL) fatty acid content of platelets, aorta and heart was determined by gas
      liquid chromatography, and the in vitro aorta production of prostacyclin (PGI2)
      from exogenous or endogenous arachidonic acid (AA) was measured using the
      radioimmuno-assay (RIA) method. Serum thromboxane B2 (TXB2) released by platelets
      as thromboxane A2 (TXA2) during incubation of whole blood was also measured by
      this method. In the group fed CF, AA was significantly lower in the PL of aorta,
      platelet and heart, and the ratio 20:3(n-9)/20:4(n-6) was greater than in the
      groups fed CO, B or HF, indicating that the group fed CF was essential fatty acid
      (EFA) deficient. Although AA was significantly lower in the aorta and platelet PL
      of the group fed HF compared to the group fed CO, that difference did not affect
      the amounts of PGI2 or TXB2 produced in these groups. The group fed CF had
      significantly less PGI2 and TXB2 released by aorta and platelets than the other
      groups. This was the result of the reduced level of AA and the presence of higher
      amounts of 20:3(n-9) acid in the PL, which might act as a competitive inhibitor
      for cyclooxygenase. The aortic production of PGI2 from exogenous AA did not
      differ among the groups indicating that prostaglandin synthetase was not affected
      by the dietary fat. We conclude that the consumption of hydrogenated fats high in
      trans 18:1 acids with adequate amount of linoleic acid had no effect on the
      amount of thromboxane or prostacyclin produced by platelet or aorta in vitro.

PMID- 9915871
TI  - Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells.
AB  - The human hepatoma HepG2 cell line was chosen as a representative of solid tissue
      derived cell systems in which folate metabolism and apoptosis induction have not
      been thoroughly investigated. HepG2 cells were cultivated in the control or
      folate-deficient media (control media lacking of folate, glycine, thymidine and
      hypoxanthine) for 4 wk. This resulted in a decrease in intracellular folate
      levels to 32% of the control within 1 wk, which was followed by growth arrest and
      greater cell death rates. These disturbances of folate deficiency coincided with
      apoptotic induction, as characteristically shown by nucleosomal DNA fragmentation
      of 180-200 base pair multimers, nuclear chromatin condensation and positive
      terminal transferase-mediated dUTP nick end labeling assay. Apoptosis coincided
      with an accumulation of cells in S-phase, a subsequent G2/M phase block and a
      significant increase in mean protein content as evaluated by flow cytometric
      analyses employing a double-staining method. The growth and cell cycle arrest
      under folate-deficient conditions was independent of a change of p53 expression
      as measured by an enzyme-linked immunosorbent assay. Supplementation of 2
      micromol/L folate normalized cell cycles and diminished DNA fragmentation. Taken
      together, these data indicate that HepG2 cells cultivated in folate-deficient
      medium have a low folate concentration, decreased growth and viability, and
      increased apoptotic propensity. This occurrence of apoptosis was associated with
      a cell cycle-specific mechanism and independent of p53-mediated pathway.

PMID- 9915872
TI  - Dietary conjugated linoleic acid influences the immune response of young and old
      C57BL/6NCrlBR mice.
AB  - Aging is associated with a decline in the immune response in mammals. Conjugated
      linoleic acid (CLA) has been suggested to have immunoenhancing properties. We
      examined the influence of dietary CLA on the immune response of young and old
      mice. Forty young (4 mo) and 40 old (22 mo) mice consumed ad libitum diets
      containing 0 or 1 g CLA /100 g for 8 wk. Splenocytes from half of the mice were
      isolated to evaluate proliferation to concanavalin A (Con A) (0.5, 1.5, 5.0 mg/L)
      and phytohemagglutinin A (PHA) (5, 20, 40 mg/L) and lipopolysaccharide (LPS) (5,
      15, 30 mg/L), natural killer cell (NK) activity and prostaglandin (PG)E2 and
      interleukin (IL)-2 production. The remaining mice were used to evaluate in vivo
      delayed-type hypersensitivity (DTH) skin response. There was a significant
      decline due to age in response to all three mitogens tested (P < 0. 05). CLA
      supplementation significantly increased all CLA isomers measured in hepatic
      neutral lipids and phospholipids (P < 0.05). Young mice fed 1% CLA had greater
      splenocyte proliferation in response to Con A (0.5 and 5.0 mg/L) and PHA (40
      mg/L) (P < 0.05) than young mice fed control diet. Old mice fed 1 g CLA/100 g had
      significantly higher proliferative response to optimal concentrations of Con A
      (1.5 mg/L) (P < 0.001) than the mice fed the control diet. Old mice fed the
      control diet had significantly lower splenocyte IL-2 production than the young
      mice (P < 0.005). CLA-supplemented young mice had significantly higher splenocyte
      IL-2 production than those fed the control diet (P < 0.05). CLA had no effect on
      NK cell activity, PGE2 production or DTH in young or old mice. Further studies
      are needed to determine the mechanism of CLA-induced enhancement of IL-2
      production and T cell proliferation.

PMID- 9915873
TI  - Ingestion of guar gum hydrolysate, a soluble fiber, increases calcium absorption
      in totally gastrectomized rats.
AB  - Gastrectomy induces osteopenia. We examined the effects of feeding a diet
      containing soluble dietary fiber, guar gum hydrolysate (GGH, 50 g/kg diet), on
      intestinal calcium absorption and bone mineralization in totally gastrectomized
      (Roux-en-Y esophagojejunostomy) rats by comparing them with those in two control
      groups (laparotomized and bypassed rats). In the bypassed rats, chyme bypassed
      the duodenum and upper jejunum without gastrectomy. In a second separate
      experiment, we compared calcium absorption and bone mineralization in the
      gastrectomized rats fed diets containing soluble and insoluble calcium salts and
      in bypassed rats fed insoluble calcium. In Experiment 1, apparent absorption of
      calcium supplied as a water-insoluble salt was more than 50% lower in
      gastrectomized rats than in the intact (laparotomized) or bypassed rats 3 wk
      after the start of feeding the test diets (P < 0.05). Calcium absorption was
      higher (P < 0.05) in gastrectomized rats fed the GGH diet than in those rats fed
      the GGH-free diet. In Experiment 2, absorption of soluble calcium in the
      gastrectomized rats did not differ from the absorption of calcium from calcium
      carbonate by bypassed rats. The soluble calcium pool in the cecal contents was
      significantly lower in gastrectomized rats (Experiment 1) than in intact or
      bypassed control rats, and was higher (P < 0.05) in the GGH-fed gastrectomized
      rats than in those fed the GGH-free diet. However, calcium absorption correlated
      most closely (r = 0.787, P < 0.01) with cecal propionic acid concentration. The
      femur calcium content was significantly lower in gastrectomized rats fed
      insoluble calcium than in bypassed rats fed the same diet, but was partially
      restored in the rats fed soluble calcium (Experiment 2). Bone calcium was not
      increased by feeding GGH in gastrectomized rats (Experiment 1). We conclude that
      the severely diminished calcium absorption following total gastrectomy is totally
      due to a decrease in calcium solubilization, and feeding GGH partially restores
      calcium absorption. The decrease in bone calcium that occurs as a result of
      gastrectomy is mainly due to diminished intestinal calcium absorption.

PMID- 9915874
TI  - Oral triacylglycerols regulate plasma glucagon-like peptide-1(7-36) and insulin
      levels in normal and especially in obese rats.
AB  - In a previous study of glucose tolerance, plasma insulin levels were greatly
      elevated in genetically obese Wistar fatty rats but not lean rats fed a diet
      containing polyunsaturated fatty acids. In the present study, triacylglycerol
      regulation of levels of circulating insulin and glucagon-like peptide-1 (7-36)
      (GLP-1) has been investigated in these rats. In the glucose tolerance test, the
      two plasma insulin peaks appeared in obese and lean rats intubated with glucose +
      corn oil, at 15- 30 min and 4 h, whereas only the first peak appeared in rats
      intubated with glucose alone, although the glucose response did not differ. After
      intubation of corn oil only, the insulin peak at 15 min was not detected but the
      peak at 4h was large. The two plasma GLP-1 peaks appeared 15 min and 4 h after
      intubation of glucose + corn oil similarly to the insulin responses, although the
      first peak was small and the second peak was very large. A small peak at 15 min
      was not significant in rats intubated glucose alone and no peak was seen at 4 h.
      The GLP-1 concentrations were significantly higher in the following order: portal
      vein > inferior vena cava > tail vein. The plasma GLP-1 increment in response to
      oral triacylglycerols was significantly higher in obese rats than in lean rats as
      was the insulin increment. Thus, oral triacylglycerols (possibly polyunsaturated)
      appeared to act at the gut lumen to stimulate GLP-1 secretion, which may be
      responsible for the second (4 h) insulin peak.

PMID- 9915875
TI  - Transgenic hypersecretion of des(1-3) human insulin-like growth factor I in mouse
      milk has limited effects on the gastrointestinal tract in suckling pups.
AB  - We tested the hypothesis that chronic ingestion of increased concentrations of
      milk-borne des(1-3) human insulin-like growth factor-I (hIGF-I) stimulates
      gastrointestinal growth and development in suckling mice. We used a transgenic
      mouse with targeted, lactation-dependent, overexpression of des(1-3) hIGF-I in
      the mammary gland (IGF). Pups were suckled (7 pups per litter) from birth by
      either IGF (n = 3-6 litters) or control (n = 3-5 litters) dams. In IGF and
      control pups, we measured the growth (protein and DNA content) and protein
      synthesis rate (3H-phenylalanine incorporation) of gastrointestinal and visceral
      organs in 4-, 8-, 12-, 16- and 29-d-old pups. Des(1-3) hIGF-I in milk from IGF
      dams was 40-200-fold higher than mouse IGF in either IGF or control dams, but was
      not detected in the plasma of pups suckling IGF dams. Small intestinal weight,
      protein and DNA content at 8 and 16 d were greater in pups suckling IGF dams than
      control dams; protein synthesis was also greater in IGF pups at 8 d. Total
      intestinal lactase activity at 8 and 12 d of age tended to be higher (P < 0.10)
      in IGF than in control pups. Hypersecretion of des(1-3) hIGF-I in milk ingested
      by suckling mice pups had limited effects on the growth and maturation of the
      gastrointestinal tract. Moreover, there was little evidence that milk-borne IGF-I
      is absorbed into the circulation and stimulates visceral organ growth. This study
      also demonstrates the feasibility of using mammary-specific transgenes to
      increase the concentration of milk-borne growth factors to examine whether they
      affect the growth and development of the suckling neonate.

PMID- 9915876
TI  - Inhibition of glutamine synthetase decreases proliferation of cultured rat
      intestinal epithelial cells.
AB  - The importance of glutamine synthetase (GS) for cell proliferation was examined
      in rat intestinal crypt cells (IEC-6) by inhibiting its activity with 10 mmol/L
      methionine sulfoximine (MS) at varying extracellular glutamine (Q)
      concentrations. In uninhibited cultures, cell number, protein, and DNA
      accumulation and synthesis showed a dependence on extracellular Q over a
      concentration range of 0.06 to 1.06 mmol/L, with apparent half-maximal responses
      of 0.46 mmol/L extracellular Q. In contrast, proliferation of GS-inhibited
      cultures required >/=1.06 mmol/L extracellular Q, with an apparent half-maximal
      response of 2 mmol/L. MS inhibited GS activity >97% in extracts of washed cells
      and appeared to be specific because its effects on proliferation were overcome by
      4.06 mmol/L Q and were reversible. The increased dependence of IEC-6 cells on
      extracellular Q when GS was inhibited suggests that Q derived from GS (GS-Q)
      contributes importantly to cell proliferation at physiologic levels of
      extracellular Q (0.6 mmol/L). The unexpectedly high concentration of
      extracellular Q required to rescue maximal proliferation during GS-inhibition,
      relative to a reported Km for Q-transport into the cell, indicates that
      intracellular Q derived from the extracellular medium (exo-Q) is inefficiently
      utilized. In a previous study, we found that GS-protein and mRNA are concentrated
      in the proliferative crypt region of the small intestine in vivo, and predicted
      that GS activity is important for crypt cell proliferation. Here, we show that
      enzyme activity is important for cell proliferation at physiologic concentrations
      of Q in this cell culture model. Finally, we speculate that exo-Q and GS-Q are
      utilized differently in the cell.

PMID- 9915877
TI  - The chemical form of selenium influences 3,2'-dimethyl-4-aminobiphenyl-DNA adduct
      formation in rat colon.
AB  - There is increasing evidence that selenium can protect against tumorigenesis or
      preneoplastic lesion development induced by chemical carcinogens. This study
      examined whether selenite, selenate or selenomethionine would be protective
      against 3, 2'-dimethyl-4-aminobiphenyl (DMABP)-DNA adduct formation in the liver
      and colon of rats and sought to delineate the mechanism for the protective
      effects of the different chemical forms of selenium against aberrant crypt
      formation, a preneoplastic lesion for colon cancer. After injection of DMABP, two
      DNA adducts were identified in the liver and colon of rats. Supplementation with
      either 0.1 or 2.0 mg selenium/kg diet as either selenite or selenate but not
      selenomethionine resulted in significantly fewer (53-70%; P < 0.05) N
      (deoxyguanosin-8-yl)-(deoxyguanosin-8-yl)-3, 2'-dimethyl-4-aminobiphenyl (C8
      DMABP)-DNA adducts in the colon but not the liver than in rats fed a selenium
      deficient diet. Rats supplemented with selenomethionine had greater (P < 0.05)
      plasma and liver selenium concentrations and glutathione peroxidase activity than
      those supplemented with selenite or selenate; however, they also had more DMABP
      DNA adducts. The protective effect of selenite and selenate against DMABP-DNA
      adduct formation apparently is not a result of alterations in plasma or liver
      selenium concentrations or altered glutathione peroxidase or glutathione
      transferase activities but may be related to differences in the metabolism of the
      different forms of selenium.

PMID- 9915879
TI  - Bacteria used for the production of yogurt inactivate carcinogens and prevent DNA
      damage in the colon of rats.
AB  - Lactic acid-producing bacteria prevent carcinogen-induced preneoplastic lesions
      and tumors in rat colon. Because the mechanisms responsible for these protective
      effects are unknown, two strains of lactic acid bacteria, Lactobacillus
      delbrueckii ssp. bulgaricus 191R and Streptococcus salivarius ssp. thermophilus
      CH3, that are used to produce yogurt, were investigated in vitro and in vivo to
      elucidate their potential to deactivate carcinogens. Using the "Comet assay" to
      detect genetic damage, we found that L. bulgaricus 191R applied orally to rats
      could prevent 1, 2-dimethylhydrazine-induced DNA breaks in the colon in vivo,
      whereas St. thermophilus CH3 were not effective. However, in vitro, both strains
      prevented DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in
      isolated primary rat colon cells. Extracts prepared from milk fermented with St.
      thermophilus CH3 were as efficient in deactivating MNNG as was L-cysteine.
      Isolated metabolites arising from bacteria during fermentation in the colon or in
      milk [L(+) lactate, D(-) lactate, palmitic acid and isopalmitic acid] were not
      effective. We postulate that thiol-containing breakdown products of proteins, via
      catalysis by bacterial proteases, could be one mechanism by which MNNG or other
      carcinogens are deactivated in the gut lumen resulting in reduced damage to
      colonic mucosal cells.

PMID- 9915878
TI  - The hypotensive effect of docosahexaenoic acid is associated with the enhanced
      release of ATP from the caudal artery of aged rats.
AB  - Fish oils have been shown to lower blood pressure in hypertensive subjects. To
      determine the mechanism of this hypotensive effect, we examined the effects of
      docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish
      oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP,
      AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats
      (100 wk) were fed a high cholesterol diet and were administered intragastrically
      ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA
      group) or vehicle alone (control group). Compared with the controls, rats
      supplemented with DHA had significantly greater (10.1%) DHA concentrations in the
      caudal arteries. This was associated with more total (n-3) arterial fatty acids,
      a greater unsaturation index of arterial fatty acids, 43.9% lower plasma
      noradrenaline levels and the repression of the elevation in blood pressure
      observed with advancing age. The amount of purines released, both spontaneously
      and in response to noradrenaline, from arterial segments of DHA-supplemented rats
      was significantly higher than that released from tissues of control rats.
      Regression analysis revealed significant negative relationships between the total
      amount of purines released from the artery and the systolic (SBP) and diastolic
      (DBP) blood pressures. These results suggest that in aged rats, supplementation
      with DHA alters the membrane fatty acid composition as well as the amount of ATP
      released from vascular endothelial cells and decreases plasma noradrenaline, and
      that these factors may ameliorate the rise in blood pressure normally associated
      with advancing age.

PMID- 9915880
TI  - Vitamin C deficiency in guinea pigs differentially affects the expression of type
      IV collagen, laminin, and elastin in blood vessels.
AB  - Vitamin C deficiency causes morphologic changes in the endothelial and smooth
      muscle compartments of guinea pig blood vessels. Endothelial cells synthesize the
      basement membrane components, type IV collagen and laminin, and smooth muscle
      cells synthesize elastin in blood vessels. Therefore, we examined the possibility
      that vitamin C deficiency affects the expression of these proteins. Decreased
      expression of types I and II collagens in other tissues of vitamin C-deficient
      guinea pigs is associated with weight loss and the consequent induction of
      insulin-like growth factor binding proteins; thus we also used food deprivation
      to induce weight loss. Female guinea pigs received a vitamin C-free diet,
      supplemented orally with ascorbate. Vitamin C-deficient guinea pigs received the
      same diet but no ascorbate, and the food-deprived group received no food, but
      were supplemented with vitamin C. Concentrations of mRNAs for basement membrane
      components and elastin in blood vessels were measured by Northern blotting;
      overall basement membrane metabolism was assessed by measuring immunoreactive
      laminin and type IV 7S collagen in serum. Laminin mRNA in blood vessels and serum
      laminin concentrations were unaffected by vitamin C deficiency. Concentrations of
      type IV collagen and elastin mRNAs in blood vessels were not significantly
      affected in moderately scorbutic guinea pigs (0-7% weight loss), but with
      increased weight loss, type IV collagen mRNA was 57% (P < 0.05) and elastin mRNA
      was 3% (P < 0. 01) of normal values. In food-deprived guinea pigs, type IV
      collagen mRNA was 51% (P < 0.05) and elastin mRNA was 35% (P < 0.05) of normal.
      Serum type IV 7S collagen concentrations were 25% of normal in scorbutic guinea
      pigs with extensive weight loss. The lower expression of type IV collagen and
      elastin mRNAs in blood vessels may contribute to defects observed in blood
      vessels during scurvy.

PMID- 9915881
TI  - Conjugated linoleic acid inhibits proliferation but stimulates lipid filling of
      murine 3T3-L1 preadipocytes.
AB  - This study documented the effects of conjugated linoleic acid (CLA) on the
      proliferation and differentiation of 3T3-L1 preadipocytes. During proliferation,
      preadipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM), 100 g/L
      fetal bovine serum (FBS), 0. 584 g/L L-glutamine and 0 (control), 0.5, 1.0, 5.0
      or 10.0 mg/L CLA. Proliferation of 3T3-L1 preadipocytes was measured directly by
      cell counting and indirectly by radiolabeled thymidine incorporation into DNA at
      96 h postinoculation. Conjugated linoleic acid was not cytotoxic during
      proliferation or differentiation. The 0.5, 1.0, 5.0 or 10.0 mg/L CLA treatments
      inhibited proliferation by 8, 12, 31 and 36%, respectively (all P < 0.05).
      Treatment with 10 mg/L CLA or 10 mg/L linoleic acid (cis-9,12) reduced the
      incorporation of 3H-thymidine into DNA by 56 and 35%, respectively, suggesting
      that some portion of the effect of CLA on preadipocyte proliferation was
      nonspecific. After the initiation of differentiation, preadipocytes were cultured
      in DMEM, 100 g/L FBS, 0.584 g/L L-glutamine, 1.7 micromol/L insulin and 0
      (control), 0.5, 1.0, 5.0 or 10.0 mg/L CLA. Radiolabeled glucose incorporation
      into cellular lipids was increased from 7.4 to 11.1, 11.1, 17.4 and 22.5
      nmol/(h.10(6 )cells) (all P < 0.05) by 0.5, 1.0, 5.0 and 10.0 mg/L CLA,
      respectively. A media concentration of 10 mg/L CLA increased total cellular CLA
      (from 0 to 0.16 +/- 0.01 micromol/10(6 )cells), palmitic acid (from 0.47 to 1.10
      +/- 0.03 micromol/10(6 )cells) and palmitoleic acid (from 0.24 to 0.81 +/- 0.03
      micromol/10(6 )cells) (means +/- pooled SEM; all P < 0.05). Conjugated linoleic
      acid had no effect on arachidonic acid content, but decreased its proportion (g
      arachidonic acid/100 g total fatty acids) by >50% (P < 0.05). These data indicate
      that CLA inhibited proliferation and promoted de novo lipogenesis and lipid
      filling in 3T3-L1 preadipocytes, suggesting that CLA may reduce overall fat
      accumulation in growing animals by inhibiting stromal vascular preadipocyte
      hyperplasia.

PMID- 9915882
TI  - Reciprocal regulation of HFE and NNamp2 gene expression by iron in human
      intestinal cells.
AB  - The newly identified hemochromatosis gene, HFE, and a candidate iron transporter
      gene, Nramp2, have been proposed as key factors responsible for the regulation of
      intestinal iron absorption. Although the exact functions of these proteins in
      intestinal iron absorption are unknown, HFE may be required for the down
      regulation of iron absorption that occurs with increasing iron status, and Nramp2
      may up-regulate iron absorption when iron status is low. Thus, we examined
      whether the expression of the HFE and Nramp2 genes are regulated by iron status
      in the human intestinal cell line Caco-2. HFE mRNA and HFE protein were increased
      and Nramp2 mRNA was decreased by increasing cellular iron status in Caco-2 cells.
      This iron-mediated modulation of mRNA levels was specific to iron. Moreover,
      super-induction of HFE mRNA in the presence of cycloheximide suggests that HFE
      gene expression may be controlled by a short-lived repressor protein. HFE and
      Nramp2 mRNA levels also changed in opposite directions during cellular
      differentiation. This reciprocal modification of the HFE and Nramp2 gene
      expression during both iron treatment and cell differentiation in Caco-2 cells is
      consistent with an opposing role for these proteins in homeostatic regulation of
      human intestinal iron absorption.

PMID- 9915883
TI  - A carbohydrate-rich diet stimulates glucose-6-phosphate dehydrogenase expression
      in rat hepatic sinusoidal endothelial cells.
AB  - A carbohydrate-rich diet induces glucose-6-phosphate dehydrogenase (G6PD) in
      liver parenchymal cells, which supports fatty acid synthesis de novo. Bacterial
      endotoxins stimulate G6PD expression in hepatic sinusoidal endothelial and
      Kupffer cells but not in parenchymal cells. This study was designed to elucidate
      whether G6PD expression is regulated uniformly by dietary carbohydrates in
      hepatic sinusoidal and parenchymal cells. Freshly isolated cells from five groups
      of Sprague-Dawley rats were analyzed for G6PD activity and mRNA abundance. The
      rats were grouped as follows: 1) food deprived for 24 h; 2) food deprived for 24
      h followed by consumption of the standard diet for 48 h; 3) food deprived for 24
      h followed by consumption of a carbohydrate-rich diet for 48 h; 4) fed standard
      diet; and 5) fed standard diet followed by consumption of a carbohydrate-rich
      diet for 48 h. In endothelial cells, G6PD activity was 150% greater in group 3
      than in group 1 and 125% greater in group 5 than in group 4. Steady-state G6PD
      mRNA levels were elevated by 300% in endothelial cells from group 3 compared with
      those from group 1. In Kupffer cells, G6PD activity and mRNA abundance were not
      different among the groups. As expected, G6PD expression was 700-1200% greater in
      parenchymal cells from rats fed a carbohydrate diet (groups 3 and 5) than from
      controls. Our results indicate that short-term consumption of a carbohydrate-rich
      diet stimulates G6PD expression in endothelial and parenchymal cells. Because
      G6PD supports reactive oxygen metabolism, the response may represent a
      preconditioning of antioxidant pathways in the hepatic cell populations that are
      targets of sinusoid-born reactive oxygen species during infections.

PMID- 9915884
TI  - Vitamins C and E prolong time to arterial thrombosis in rats.
AB  - To examine the modulation of arterial thrombosis by vitamins C and E, Sprague
      Dawley rats were fed nonpurified diet, or diet mixed with vitamin C [100 mg/(kg
      body weight.d)], vitamin E [100 mg/(kg.d)] or both vitamins C and E [each 100
      mg/(kg.d)], for a period of 9-19 d (mean 15 d). An occlusive aortic thrombus was
      created by application of a Whatman filter soaked in 1 mol/L FeCl3. Both vitamins
      C and E and their combination decreased platelet aggregation and delayed time to
      occlusive thrombus formation (P < 0.05 vs. control). Vitamins C and E decreased
      arterial superoxide generation (P < 0.05 vs. control). Interestingly, vitamin E
      also increased endogenous superoxide dismutase activity (SOD) and protein
      expression in aortic tissues (P < 0.05 vs. control). The combination of vitamins
      C and E was not superior to each vitamin alone with regard to effect on time to
      thrombus formation, but it was more potent with regard to platelet inhibition.
      The increase in endogenous antioxidant activity by vitamin E is an intriguing
      observation. This study shows that the antioxidant vitamins C and E have
      important effects on platelet aggregation, SOD activity, superoxide generation
      and thrombus formation.

PMID- 9915885
TI  - Short-chain fructo-oligosaccharide administration dose-dependently increases
      fecal bifidobacteria in healthy humans.
AB  - Short-chain fructo-oligosaccharides (SC-FOS) are a mixture of oligosaccharides
      consisting of glucose linked to fructose units (Gfn; n = </= 4), which are not
      digested in the human small intestine but are fermented in the colon where they
      specifically promote the growth of bifidobacteria. In healthy volunteers, we
      assessed the tolerance and the threshold dose of SC-FOS that significantly
      increased fecal bifidobacteria counts and the possibility of a dose-response
      relationship. Randomly divided into five groups and eating their usual diets,
      healthy volunteers (40: 18 males, 22 females) ingested in two oral doses for 7 d
      a powder mixture containing (g SC-FOS/d): 0, G0; 2.5, G2.5; 5, G5; 10, G10; 20,
      G20. Stools were collected before (d1) and at the end (d8) of sugar consumption,
      and tolerance was evaluated using a daily chart. Total anaerobe counts were not
      affected by SC-FOS ingestion. Bifidobacteria counts at d8 were greater in groups
      G10 and G20 than in G0 and G2.5 (P < 0.05). Fecal pH did not differ among groups.
      A significant correlation between the dose of SC-FOS ingested and the fecal
      bifidobacteria counts was observed at d8 (r = 0.53; P < 0.01). Excess flatus was
      significantly more frequent in subjects consuming G20 than in those consuming G0,
      G2.5 or G5 (P < 0.05), and more intense in G20 than in G0 and G5 groups (P <
      0.05). In conclusion, the optimal and well-tolerated dose of SC-FOS that
      significantly increased fecal bifidobacteria in healthy volunteers consuming
      their usual diet is 10 g/d.

PMID- 9915886
TI  - Iron is well absorbed by healthy adults after ingestion of double-fortified (iron
      and dextran-coated iodine) table salt and urinary iodine excretion is unaffected.
AB  - Severe deficiencies of iron (Fe) and iodine (I) affect more than one third of the
      world's population. A table salt, fortified with I and Fe, would be useful in
      areas in which anemia and goiter coexist. However, interactions between the two
      minerals have prevented their simultaneous use as fortificants. A method has been
      developed to coat I with dextran such that after spraying onto table salt, Fe and
      I do not interact. Our objective was to determine the absorption of Fe and the
      urinary excretion of I from table salt when provided in meals designed to
      significantly inhibit or enhance Fe absorption. Subjects (n = 16) ingested Fe
      enhancing and Fe-inhibiting meals containing 5 g of table salt with 0.39 micromol
      dextran-coated I as potassium iodide and 1 mg of Fe (ferrous fumarate labeled
      with 59Fe) per gram of salt. Subjects also received a reference dose of 3 mg of
      ferrous fumarate labeled with 59Fe to "correct" for interindividual variation in
      iron absorption at a later date. Measured by whole-body counting, Fe-absorption
      from the Fe-enhancing meal (36.2 +/- 12.0%, corrected; 13.5 +/- 13.8%
      uncorrected) was significantly higher than that from the Fe-inhibiting meal (7.4
      +/- 11.3%, corrected; 4.0 +/- 8.4%, uncorrected) (P < 0.0001). Urinary excretion
      of iodine at baseline and postingestion were not significantly different (0.89 +/
      0.5 vs. 1.06 +/- 0.39 micromol/L, P < 0.47) and were within the normal range. We
      conclude that Fe was well absorbed but influenced by the composition of the meal
      and that urinary excretion of iodine was maintained in the normal range with
      dextran-coated iodine.

PMID- 9915887
TI  - Taste sensitivity is altered in patients with chronic renal failure receiving
      continuous ambulatory peritoneal dialysis.
AB  - Decreased taste sensitivity may be one of the many factors influencing the poor
      nutritional status of many patients with chronic renal failure. Several studies
      examining taste in chronic uremic and hemodialysis (HD) patients indicate
      decreased sensitivity; continuous ambulatory peritoneal dialysis (CAPD) patients,
      however, warrant investigation. The aim of this study was to determine if the
      taste detection threshold for each of the four tastes (sweet, salty, sour and
      bitter) differs between CAPD patients and age and sex matched controls with
      normal renal function. The thresholds were determined using Cornsweet's staircase
      technique for increasing and decreasing stimulus concentration, in which the
      subject's response determines the next concentration to be tested. A forced
      choice design using three samples was used to help minimize bias. The taste
      detection threshold for the CAPD patients was significantly higher than that of
      the controls for sodium chloride (salty)(P = 0.001) and quinine (bitter) (P =
      0.01). This information may be useful when designing dietary supplements and
      devising meal plans to help patients consume nutritionally adequate diets.

PMID- 9915888
TI  - Preparation of chylomicrons and VLDL with monoacid-rich triacylglycerol and
      characterization of kinetic parameters in lipoprotein lipase-mediated hydrolysis
      in chickens.
AB  - To identify the substrate specificity of lipoprotein lipase (LPL) for
      triacylglycerol-rich lipoproteins with monoacid-rich triacylglycerols, monoacid
      rich lipoproteins were prepared and kinetic parameters of LPL were characterized.
      Male broiler chickens were fed 8 g/100 g fat diets differing only in the fat
      source: palm oil (tripalmitin-rich), olive oil (triolein-rich), safflower oil
      (trilinolein-rich) and linseed oil (trilinolenin-rich). After diets were fed for
      3 d, chickens were starved for 2 d and then force-fed emulsions containing one of
      the monoacid-triacylglycerols: tripalmitin, triolein, trilinolein or
      trilinolenin. The triacylglycerols in chylomicrons and very low density
      lipoprotein (VLDL) of chickens force-fed tripalmitin, triolein or trilinolein
      contained the corresponding acid at more than 70% of total acids. Linolenic acid
      was incorporated into chylomicrons and VLDL to a lower extent (51.2 and 57.2%,
      respectively) in chickens force-fed trilinolein. Major apolipoproteins and lipid
      compositions were not significantly different among all lipoproteins isolated
      from chickens fed the different fats. Vmax of LPL was significantly higher (P <
      0.05) for palmitic acid-rich chylomicrons and VLDL and decreased with increasing
      chain length and unsaturation of monoacid: 16:0>18:1>18:2>18:3. The electron spin
      resonance analysis, order parameter (S), decreased with monoacid chain length and
      unsaturation. In addition, the Vmax of LPL increased linearly (P < 0.01, r = 0.
      912) with an increase in the palmitic acid content of the lipoprotein
      triacylglycerols. These findings suggest that lipoprotein catalysis by LPL is
      modulated by the palmitic acid content of the lipoprotein triacylglycerol, which
      affects the fluidity of lipoproteins.

PMID- 9915889
TI  - Type of milk consumed can influence plasma concentrations of fatty acids and
      minerals and body composition in infant and weanling pigs.
AB  - Two experiments using 42 crossbred neonatal pigs to compare the effects of
      caprine and bovine milk on growth, apparent nutrient digestibility and body
      composition were conducted. At age 72 h, pigs were removed from their dams and
      randomly divided into two groups, housed separately in stainless steel metabolism
      cages and were fed a predetermined amount (300 mL/kg body weight) of pasteurized,
      nonfortified whole, caprine or bovine milk. Body composition was determined using
      dual energy X-ray absorptiometry (DXA). In Experiment 1, 22 intact male pigs were
      used for a 31-d experimental period. There was no significant (P > 0.05) dietary
      effect on growth, apparent nutrient digestibility or body composition.
      Significant differences (P < 0.05), however, were observed in plasma of C 8:0, C
      10:0 and C 12:0 concentrations. In Experiment 2, 20 pigs (10 intact males and 10
      females) were used in a 2 x 2 factorial experiment for 52 d. Pigs fed caprine
      milk had higher (P < 0.05) plasma concentrations of C10:0 and C12:0 as well as
      Na, Mg and Zn than those fed bovine milk. At Day 52, pigs fed caprine milk had
      less body fat (P < 0.001) and higher (P < 0.06) bone mineral density than those
      fed bovine milk. Drymatter, N and total mineral intake of male pigs was higher (P
      < 0.05) than female pigs. Also, male pigs had higher (P < 0.05) plasma
      concentrations of C12:0 than females. This study demonstrates that the type of
      milk consumed can influence plasma concentrations of fatty acids, minerals and
      body composition in pigs.

PMID- 9915890
TI  - Somatotropin regulates adipose tissue metabolism in neonatal swine.
AB  - Somatotropin (ST) reduces lipid deposition in growing and adult animals, but its
      effect in neonatal pigs is not clear. In this study, we tested the hypothesis
      that ST inhibits lipid deposition in neonatal pig adipose tissue. Four neonatal
      (2.9 +/- 0.1 kg, 7 d of age) and four growing (17.0 +/- 1.4 kg, 60 +/- 3 d of
      age) crossbred pigs were used. Subscapular adipose tissue fragments were cultured
      with or without ST (4.5 nmol/L) for 24 h in the absence or presence of insulin (7
      nmol/L). After culture for 24 h with insulin alone, adipocytes from neonatal and
      growing pig adipose tissue maintained the capacity to incorporate glucose into
      total lipid at rates comparable to those in fresh tissue. Culture for 24 h with
      ST in the presence or absence of insulin decreased adipocyte glucose
      incorporation into fatty acids. Addition of ST, in the absence or presence of
      insulin, also increased the accumulation of glycerol in the medium during culture
      of neonatal and growing pig adipose tissue. Furthermore, culture for 24 h with ST
      resulted in higher basal lipolysis measured during incubation of isolated
      adipocytes in the presence of adenosine deaminase. In addition, culture with ST
      decreased adipose tissue lipoprotein lipase (LPL) activity and completely blocked
      the stimulatory effect of insulin on activity of this enzyme. The present study
      is the first to demonstrate in neonatal pigs that, as in growing pigs, ST
      regulates adipose tissue metabolism through decreasing lipid synthesis and LPL
      activity and increasing lipolysis. Thus, ST may play an important role in
      nutrient partitioning during the neonatal period.

PMID- 9915891
TI  - Hepatic fatty acid oxidation enzyme activities are stimulated in rats fed the
      brown seaweed, Undaria pinnatifida (wakame).
AB  - The activities of hepatic enzymes involved in fatty acid synthesis and oxidation
      were compared in rats fed diets containing different proportions of dried powder
      of the brown seaweed, Undaria pinnatifida (wakame). Rats were fed diets
      containing 0, 0.5, 1.0, 2. 0, 5.0 and 10 g/100 g of dried wakame powder.
      Experimental diets were adjusted to provide consistent amounts of most nutrients,
      but mineral concentrations were not standardized. After the 21-d feeding period,
      serum and liver triacylglycerol levels in rats fed diets in which wakame
      constituted at least 2% were significantly lower than those in rats fed the
      control diet. The activity of glucose-6-phosphate dehydrogenase was significantly
      lower in rats fed the 5 and 10% wakame diets than in rats fed the control diet.
      In contrast, 10% wakame diet increased activities of enzymes involved in the beta
      oxidation pathway including hepatic carnitine palmitoyltransferase, acyl-CoA
      dehydrogenase, acyl-CoA oxidase, enoyl-CoA hydratase and 2,4-dienoyl-CoA
      reductase. Some differences were detected in rats fed 5% wakame as well. These
      results suggest that alterations of the activities of enzymes involved in fatty
      acid metabolism in the liver are responsible for the serum triacylglycerol
      lowering effect of dietary wakame. Thus, wakame may be useful as a food to
      prevent hyperlipidemia.

PMID- 9915892
TI  - Identification of an alpha2-macroglobulin receptor in human mammary epithelial
      cells.
AB  - Several cases of zinc (Zn) deficiency in human infants caused by abnormally low
      concentrations of Zn in breast milk were recently reported, the underlying
      mechanism of which is not known. Alpha2-macroglobulin (alpha2-M), a major Zn
      binding ligand in serum, presents a potential vehicle for mammary Zn uptake. This
      study was conducted to determine if an alpha2-M receptor is present in human
      mammary epithelial cells, where it may be involved in the endocytosis of alpha2-M
      into the mammary gland. Normal human mammary epithelial cells were grown to
      confluency in serum-free medium. For all binding and uptake studies, alpha2-M,
      preactivated with methylamine and labeled with 125I, was added to cells for
      varied lengths of time to determine saturation over time and at varied
      concentrations to determine saturation over increasing concentration of ligand.
      Nonspecific and competitive binding were measured by addition of a 100-fold molar
      excess of unlabeled alpha2-M and serum albumin or lactoferrin, respectively.
      Binding at 4 degreesC was specific for alpha2-M and approached saturation
      kinetics at 56 nmol/L. Scatchard plot analysis of the binding data demonstrated
      more than one binding site: a high affinity, saturable binding site and a low
      affinity, nonsaturable binding site. Uptake of alpha2-M at 37 degreesC was rapid
      and continuous over increasing concentrations of alpha2-M, and internalized
      alpha2-M was rapidly degraded. Results from this study present evidence for
      receptor-mediated uptake of alpha2-M in human mammary epithelial cells, which in
      turn, provides a potential mechanism for Zn acquisition by the cell.

PMID- 9915893
TI  - Trehalose can be used as a parenteral saccharide source in rabbits.
AB  - Trehalose is a saccharide that possesses no reducing group and so has possible
      use in parenteral nutrition, especially because it can be stored with amino acids
      without undergoing the Maillard reaction. To evaluate this possibility, a series
      of experiments were conducted. The activity of trehalase, an enzyme that
      metabolizes trehalose to glucose, was measured in rabbit serum and kidney.
      Conversion of trehalose to glucose and excretion of trehalose in the urine were
      measured in rabbits administered 10% trehalose intravenously. The effects on
      nutritional indices as indicators of its use as an energy source were also
      measured in rabbits infused with 8.23 g.kg-1.d-1 (4. 12 g.kg-1 on d 1) of
      trehalose for 5 d. Trehalase activity resembled maltase activity, both being high
      in the renal cortex (2.04 +/- 0.71 and 2.93 +/- 0.26 micromol.g-1.min-1,
      respectively), weak in the medulla, and undetectable in the serum. Serum glucose
      and insulin concentrations were increased significantly by trehalose infusion.
      Significant elevations were observed in serum glucose but not insulin levels by
      maltose infusion. On the other hand, urinary excretion of trehalose (1.1 +/- 2.1%
      of dose) was significantly lower than that of maltose (10.1 +/- 4.9% of dose).
      Similar effects of trehalose and maltose infusions as seen in normal rabbits
      occurred in rabbits with alloxan diabetes (urinary excretion rate, 3. 8 +/- 3.0%
      of the infused trehalose dose and 35.6 +/- 9.7% of the infused maltose dose).
      Nitrogen balance was positive in the trehalose- and glucose-infused normal
      rabbits with significant difference from the control group infused with saline,
      suggesting that trehalose was used as an energy source. These results suggest
      that trehalose has the potential for use as a saccharide source for parenteral
      nutrition.

PMID- 9915894
TI  - Calcium and oxalic acid kinetics differ in rats.
AB  - Small molecular weight calcium salts, if absorbed intact, could provide a
      nutritional source of calcium in subjects with impaired absorption of calcium by
      the saturable pathway. An understanding of the mechanism of absorption of calcium
      oxalate (as a representative salt) may be important nutritionally and
      therapeutically. The aim of the present study was to develop models to study
      absorption, distribution and retention of calcium and oxalate in rats as a basis
      for studying calcium oxalate absorption. Labeled compounds (45Ca and [14C]-oxalic
      acid) were administered to separate groups of rats orally (n = 8-11) or
      intravenously (n = 3-5) and blood was sampled for up to 240 min. Data were
      analyzed using SAAM/CONSAM. Calcium kinetics were fitted by a model with three
      compartments in the body and one absorption pathway from the intestine. By
      contrast, oxalic acid kinetics were fitted by two pools in the body and two
      absorption pathways from the intestine. Calcium and oxalic acid, therefore,
      demonstrate different absorption and distribution kinetics in rats.

PMID- 9915895
TI  - Absorption of calcium oxalate does not require dissociation in rats.
AB  - Calcium absorption is thought to occur only if calcium is in a soluble or
      dissociated form, although experimental evidence is lacking. The intestinal
      absorption of calcium oxalate, a small, neutral and virtually insoluble calcium
      salt, was elucidated in the whole body of awake rats. Suspensions of 45Ca
      ascorbate, 14C-oxalic acid and doubly labeled 45Ca-[14C]-oxalate were given by
      gavage to separate groups of rats. Following dosing, blood samples were drawn for
      up to 240 min through a previously inserted intravenous catheter. Serum was
      assayed for radioactive tracers, and data were then plotted as fraction of dose
      over time. Calcium absorption was 15% [with a loading of 0.3 mmol (15 mg)
      calcium], oxalic acid absorption was 22% and Ca-oxalate absorption was <2%.
      Appearance of 45Ca from calcium ascorbate and 14C from oxalic acid differed,
      whereas 45Ca and 14C from doubly labeled Ca-oxalate had identical serum
      appearance profiles. Therefore, we conclude that calcium oxalate was absorbed
      intact. Addition of excess, unlabeled calcium to the doubly-labeled calcium
      oxalate did not alter the relationship of the serum level of the two tracers,
      confirming absorption of calcium oxalate as the intact salt. Thus, calcium bound
      as a small, neutral, calcium salt such as calcium oxalate does not have to be
      dissociated prior to absorption. Possibly other small compounds would be
      similarly absorbed. These results alter our current understanding of calcium
      bioavailability from foods and therapeutic agents.

PMID- 9915896
TI  - Single and multiple selenium-zinc-iodine deficiencies affect rat thyroid
      metabolism and ultrastructure.
AB  - This study was conducted to evaluate the effects of single and combined
      deficiencies of Se, Zn and I on thyroid function in rats. Rats were fed amino
      acid-based diets for 6 wk starting from weaning. The diets contained either low
      or adequate amounts of these minerals. In addition to the control and control
      pair-fed groups, seven experimental groups were formed: Se deficient (Se-); I
      deficient (I-); Zn deficient (Zn-); Se and I deficient (Se-I-); Zn and I
      deficient (Zn-I-); Se and Zn deficient (Se-Zn); and Se, I and Zn deficient (Se-I
      Zn-). Serum triiodothyronine (T3) was significantly lower than in controls in Zn
      , Se-Zn- and Se-I- groups. Serum total thyroxine (T4) and free T4 were
      significantly lower and thyroid-stimulating hormone (TSH) greater in all iodine
      deficient groups, regardless of Se or Zn status. Thyroid glutathione peroxidase
      activity was significantly reduced in Se- and Se-Zn- groups. Nevertheless, in the
      groups with a concurrent I deficiency, the activity of this enzyme was
      significantly greater than in controls. Severe alterations of the follicle
      cellular architecture, including signs compatible with apoptosis, were observed
      in the Zn- and Se-Zn- groups. These alterations appeared to be less severe when
      iodine deficiency was simultaneously present. Single and multiple deficiencies of
      Se, Zn and I have distinct effects on thyroid metabolism and structure.

PMID- 9915897
TI  - 59Fe is retained from an elemental 59Fe powder supplement without effects on
      65Zinc, 47Calcium and 67Copper in young pigs.
AB  - In vivo counting with the use of a germanium detector evaluated the retention of
      an elemental 59Fe powder supplement while measuring potential interactions with
      zinc, calcium and copper. Effects of dietary iron and zinc on in vivo retentions
      of 59Fe, 65Zn, 67Cu and 47Ca were studied in young pigs. In Experiment 1, 4-d-old
      piglets fed a cereal-based diet were randomly assigned to one of four treatment
      groups (2 x 2 factorial arrangement, n = 5 per group). Variables were dietary
      iron source (either elemental iron or FeSO4, each at 100 mg iron/kg diet) and the
      dosage form of radioactive iron (either elemental 59Fe powder or 59FeSO4).
      Experiment 2 (2 x 3 factorial arrangement) was performed using two levels of iron
      (100 and 200 mg/kg, as elemental iron) and three levels of zinc (25, 50 and 100
      mg/kg). Piglets were also dosed with 47Ca, 65Zn and 67Cu; all radioisotopes were
      measured for 8 d. Apparent absorption of elemental 59Fe powder was 13 +/- 1%,
      whereas 59Fe sulfate was significantly (P < 0.05) higher at 26 +/- 1%. The FeSO4
      diet decreased 65Zn retention in Experiment 1, in contrast to the elemental iron
      diet, which did not have this effect in either experiment. Apparent 65Zn
      absorption averaged 44 +/- 2, 35 +/- 1 and 27 +/- 2% for the three levels of zinc
      (25, 50 and 100 mg/kg), respectively. Retention of 47Ca was not affected by
      dietary iron or zinc; retention of 67Cu was not affected by dietary iron. The
      data demonstrate good bioavailability of elemental iron without effects on zinc,
      copper and calcium.

PMID- 9915898
TI  - Calcium-regulating hormones, bone mineral content, breaking load and trabecular
      remodeling are altered in growing pigs fed calcium-deficient diets.
AB  - Studies on calcium nutrition in appropriate large animal models can be directly
      relevant to humans. We have examined the effect of dietary Ca deficiency on
      various bone and bone-related variables, including plasma markers,
      histomorphometry, mineral content and breaking strength in pigs. Three groups of
      eight 38-d-old female pigs were fed adequate (0.9%; control), low (0.4%; LCa) or
      very low (0.1%; VLCa) Ca diets for 32 d. Plasma Ca significantly decreased over
      time only in the VLCa-deficient pigs. The concentrations of the parathyroid
      hormones (PTH) and calcitriol increased as Ca deficiency developed, and the
      plasma PTH and calcitriol levels varied inversely with dietary Ca. The total bone
      ash contents, bending moments, trabecular bone volume and the mineral apposition
      rate all decreased as the calcium intake decreased. The osteoclast surface areas
      were greater than those of controls in both Ca-deficient groups, whereas the
      osteoblast surface areas were greater only in the VLCa group. The plasma
      osteoblast-related markers (alkaline phosphatase, carboxy-terminal propeptide of
      type I procollagen and osteocalcin) were either greater or unaffected in the Ca
      deficient pigs. The results indicate that deficient bone mineralization combined
      with an increased bone resorption led to bone loss and fragility. The differences
      in the changes in bone cells (number and activity) between LCa and VLCa groups
      might be due to differences (time and extent) of circulating PTH and calcitriol.
      The defective mineralization in both Ca-depleted groups resulted mainly from the
      lack of Ca because their osteoblast activity was either maintained or stimulated.
      The results also underline the progressive sensitivity of pigs to Ca supply and
      the usefulness of this model.

PMID- 9915899
TI  - Aurothioglucose inhibits murine thioredoxin reductase activity in vivo.
AB  - Gold (I)-containing compounds, including aurothioglucose (ATG), are potent in
      vitro inhibitors of several selenocysteine-containing enzymes. Gold compounds
      have also been shown to potentiate the virulence of several viruses in mice,
      including coxsackievirus, implicated as a possible infectious agent in Keshan
      disease. One possible mechanism by which gold compounds may be increasing the
      virulence of viral infections in mice is by acting as a selenium antagonist in
      vivo and inducing oxidative stress. To investigate the possible role of gold
      compounds in inducing oxidative stress in mice, we assessed the ability of ATG
      administered in vivo to inhibit the activity of the selenocysteine-containing
      enzymes thioredoxin reductase (TR) and glutathione peroxidase (GPX1). Doses as
      low as 0. 025 mg ATG/g body weight caused significant and prolonged inhibition of
      TR activity in all tissues examined. No such inhibition of GPX1 activity was
      seen, indicating differential in vivo sensitivity of the enzymes to inhibition by
      ATG. In liver and heart, some recovery of TR activity was observed after a 7-d
      period, but no recovery was observed in pancreas or kidney. Because TR is
      involved in several important cellular redox functions, its inhibition most
      likely will affect multiple cellular processes. These results indicate that in
      vivo administration of ATG results in significant and long-lasting inhibition of
      TR activity. Such inhibition of TR could lead to increased levels of oxidative
      stress in vivo, thereby increasing the virulence of several viruses including the
      coxsackievirus.

PMID- 9915900
TI  - Perinatal brain iron deficiency increases the vulnerability of rat hippocampus to
      hypoxic ischemic insult.
AB  - Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes
      mellitus or intrauterine growth retardation. Because neurocognitive deficits are
      more common in the offspring of these pregnancies, we tested the hypothesis that
      perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure
      important for memory processing, to injury. Brain iron concentration was reduced
      by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation.
      Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic
      ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on
      postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase
      activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided
      cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001)
      and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P =
      0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl
      substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus
      (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron
      sufficient group. No increase in right-sided free-iron staining was present in
      either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a
      greater acute loss of neuronal metabolic activity after an hypoxic-ischemic
      event, suggesting compromised cellular energetics. The subsequently greater loss
      of hippocampal neuronal integrity suggests poorer recoverability after injury in
      the perinatal iron-deficient brain.

PMID- 9915901
TI  - Fish oil supplementation prevents diabetes-induced nerve conduction velocity and
      neuroanatomical changes in rats.
AB  - Diabetic neuropathy has been associated with a decrease in nerve conduction
      velocity, Na,K-ATPase activity and characteristic histological damage of the
      sciatic nerve. The aim of this study was to evaluate the potential effect of a
      dietary supplementation with fish oil [(n-3) fatty acids] on the sciatic nerve of
      diabetic rats. Diabetes was induced by intravenous streptozotocin injection.
      Diabetic animals (n = 20) were fed a nonpurified diet supplemented with either
      olive oil (DO) or fish oil (DM), and control animals (n = 10) were fed a
      nonpurified diet supplemented with olive oil at a daily dose of 0.5 g/kg by
      gavage for 8 wk. Nerves were characterized by their conduction velocity,
      morphometric analysis and membrane Na, K-ATPase activity. Nerve conduction
      velocity, as well as Na,K-ATPase activity, was improved by fish oil treatment. A
      correlation was found between these two variables (R = 0.999, P < 0.05).
      Moreover, a preventive effect of fish oil was observed on nerve histological
      damage [endoneurial edema, axonal degeneration (by 10-15%) with demyelination].
      Moreover, the normal bimodal distribution of the internal diameter of myelinated
      fibers was absent in the DO group and was restored in the DM group. These data
      suggest that fish oil therapy may be effective in the prevention of diabetic
      neuropathy.

PMID- 9915902
TI  - Fumonisin B1 consumption by rats causes reversible, dose-dependent increases in
      urinary sphinganine and sphingosine.
AB  - Fumonisin B1 (FB1) is a frequently encountered mycotoxin that inhibits ceramide
      synthase, the enzyme that acylates sphinganine, sphingosine and other "sphingoid"
      bases. Exposure of rats, rabbits, pigs and nonhuman primates to fumonisin
      contaminated feed elevates sphingoid base amounts in urine; therefore, this study
      examined the time course and reversibility of these changes. When an AIN-76 diet
      supplemented with >/=5 microg FB1/g was fed to male Sprague-Dawley rats, there
      was a significant increase in sphinganine (ca. 50-fold in urine from rats fed 50
      microg FB1/g diet) and smaller changes in sphingosine within 5 to 7 d, compared
      to rats fed the same diet without FB1. No change occurred in sphingoid bases upon
      feeding 1 microg FB1/g for up to 60 d. When rats were fed FB1 (10 microg FB1/g
      diet for 10 d), then changed to the same diet minus FB1, urinary sphingoid bases
      returned to normal within 10 d. However, if the rats were fed 10 microg FB1/g for
      10 d, then changed to 1 microg FB1/g, the amounts of sphingoid bases in urine
      were the same as for rats that were continuously fed 10 microg FB1/g. These
      results establish that consumption of FB1 causes dose-dependent and reversible
      elevations in the amounts of urinary sphingoid bases. The finding that 1 microg
      FB1/g (which does not, alone, alter urinary sphingoid bases) will sustain the
      elevation caused by previous exposure to 10 microg FB1/g raises the possibility
      that even low levels of fumonisins could be deleterious when an animal is
      occasionally exposed to higher amounts.

PMID- 9915903
TI  - Introduction

PMID- 9915904
TI  - Keynote address.

PMID- 9915905
TI  - Muscle protein breakdown and the critical role of the ubiquitin-proteasome
      pathway in normal and disease states.

PMID- 9915906
TI  - Wasting in HIV infection and AIDS.
AB  - AIDS wasting is not characterized by a single pathophysiological process but by a
      variety of processes that operate at different times. Acute wasting tends to be
      associated with secondary infections; chronic wasting is associated with
      gastrointestinal disease. Although resting energy expenditure is increased, total
      energy expenditure is reduced in individuals who are losing weight and it is
      usually reduced intake that commonly drives wasting. However, reduced intake is
      not an adequate explanation for the metabolic abnormalities that are seen in HIV
      infection. In particular, protein metabolism and lipid metabolism are abnormal,
      possibly representing inappropriate utilization of substrates. The response to
      nutrition may be impaired, particularly in terms of accrual of lean tissue but
      nutritional support may prolong survival. The impact of protease inhibitors on
      wasting in HIV infection is yet to be fully ascertained but despite antiviral
      therapy it seems that wasting is likely to remain a problem at least in some
      patients.

PMID- 9915907
TI  - Wasting in cancer.
AB  - Progressive weight loss is a common feature of many types of cancer and is
      responsible not only for a poor quality of life and poor response to
      chemotherapy, but also a shorter survival time than is found in patients with
      comparable tumors without weight loss. Although anorexia is common, a decreased
      food intake alone is unable to account for the changes in body composition seen
      in cancer patients, and increasing nutrient intake is unable to reverse the
      wasting syndrome. Although energy expenditure is increased in some patients,
      cachexia can occur even with a normal energy expenditure. Various factors have
      been investigated as mediators of tissue wasting in cachexia. These include
      cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      interferon-gamma (IFN-gamma) and leukemia inhibitory factor (LIF), as well as
      tumor-derived factors such as lipid mobilizing factor (LMF) and protein
      mobilizing factor (PMF), which can directly mobilize fatty acids and amino acids
      from adipose tissue and skeletal muscle respectively. Induction of lipolysis by
      the cytokines is thought to result from an inhibition of lipoprotein lipase
      (LPL), although clinical studies provide no evidence for an inhibition of LPL in
      the adipose tissue of cancer patients. Instead there is an increased expression
      of hormone sensitive lipase, the enzyme activated by LMF. Protein degradation in
      cachexia is associated with an increased activity of the ATP-ubiquitin-proteasome
      pathway. The biological activity of both the LMF and PMF was shown to be
      attenuated by eicosapentaenoic acid (EPA). Clinical studies show that this
      polyunsaturated fatty acid is able to stabilize the rate of weight loss and
      adipose tissue and muscle mass in cachectic patients with unresectable pancreatic
      cancer. Knowledge of the mechanism of cancer cachexia should lead to the
      development of new therapeutic agents.

PMID- 9915908
TI  - Pathophysiology of protein-energy wasting in chronic renal failure.
AB  - There is a high prevalence of protein-energy malnutrition in both nondialyzed
      patients with advanced chronic renal failure and in those individuals with end
      stage renal disease who are receiving maintenance hemodialysis or chronic
      peritoneal dialysis therapy. Approximately one-third of maintenance dialysis
      patients have mild to moderate protein-energy malnutrition, and about 6 to 8
      percent of these individuals have severe malnutrition. These statistics are of
      major concern because markers of protein-energy malnutrition are strong
      predictors of morbidity and mortality. The causes of protein-energy malnutrition
      in patients with chronic renal failure include: (1) decreased energy or protein
      intake; (2) concurrent chronic illnesses, and superimposed acute illnesses and
      possibly increased inflammatory cytokines; (3) the catabolic stimulus of
      hemodialysis; (4) losses of nutrients into dialysate, particularly amino acids,
      peptides, protein (with peritoneal dialysis), glucose (when hemodialysis is
      performed with glucose-free dialysate) and water-soluble vitamins; and (5)
      diagnostic or therapeutic (e.g., prednisone therapy) procedures that reduce
      nutrient intake or engender net protein breakdown. Other theoretically possible
      causes for protein-energy malnutrition include (6) chronic blood loss; (7)
      endocrine disorders (especially resistance to insulin and insulin-like growth
      factor-I, hyperglucagonemia, hyperparathyroidism and deficiency of 1,25
      dihydroxycholecalciferol); (8) products of metabolism that accumulate in renal
      failure and may induce wasting, such as organic and inorganic acids; (9) loss of
      the metabolic actions of the kidney; and (10) the accumulation of toxic compounds
      that are taken up from the environment (e.g., aluminum).

PMID- 9915909
TI  - Wasting in chronic gastrointestinal diseases.

PMID- 9915910
TI  - The pathophysiology of wasting in the elderly.
AB  - Aging is associated with changes in body composition and energy and protein
      metabolism that are due both to the direct effects of aging and to the effect of
      age-related diseases. We have recently differentiated these changes under three
      categories: wasting, cachexia, and sarcopenia. We have defined wasting as
      unintentional loss of weight, including both fat and fat-free compartments.
      Experience in the HIV epidemic suggests that wasting is driven largely by
      inadequate dietary intake. Cachexia, on the other hand, refers to loss of fat
      free mass, and especially body cell mass, but with little or no weight loss. The
      metabolic hallmarks of cachexia are hypermetabolism and hypercatabolism, driven
      by inflammatory cytokine-mediated acute phase responses. Finally, sarcopenia
      refers to loss of muscle mass specifically, and seems to be an intrinsic age
      related condition. In the elderly, wasting as defined here is at the extreme end
      of the spectrum, but generally develops in the setting of pre-existing sarcopenia
      and cachexia. The challenges before us now are to better define these conditions,
      establish guidelines for their recognition, and develop better methods for
      intervening when appropriate.

PMID- 9915911
TI  - Special considerations in design of trials with elderly subjects: unexplained
      weight loss, body composition and energy expenditure.
AB  - Wasting and cachexia are significant problems in the elderly that increase
      mortality and morbidity. It is presently unclear as to the physiological
      mechanism underlying unexplained weight loss. We examine heart failure as a
      physiological model to demonstrate the importance of measuring several
      physiological outcome variables that have increased our understanding of wasting
      and cachexia in the elderly. These include the assessment of: energy expenditure,
      body composition, physical activity and exercise tolerance. We review recent data
      that has assessed energy expenditure in free-living heart failure patients using
      stable isotope methodology (doubly labeled water). Preliminary results show low
      levels of daily energy expenditure in heart failure patients due to extremely low
      levels of physical activity. Thus, a "hypermetabolic state" in free-living heart
      failure patients is not supported by these findings. The low level of physical
      activity is likely a consequence of their reduced exercise capacity and
      contributes to their skeletal muscle atrophy. This concept is support by the
      relationship between peak VO2 and muscle mass (r = 0.92; P < 0.01), as measured
      from dual energy x-ray absorptiometry. An understanding of the physiological
      factors influencing energy dysregulation and low exercise capacity may help guide
      future therapeutic interventions to restore energy balance and increase
      functional independence in patients with chronic heart failure.

PMID- 9915912
TI  - Special considerations in the design of trials involving children.

PMID- 9915913
TI  - Body composition: overview.
AB  - The following is a listing of body composition techniques now available, together
      with a brief description of the underlying assumptions and the advantages and
      disadvantages of each.

PMID- 9915914
TI  - Nutritional and metabolic endpoints.
AB  - None of the metabolic indicators which have been used to date provides a single
      or necessarily ideal endpoint for interventional management in wasting disorders.
      Some of these indicators may provide better endpoints for the acute rather than
      the chronic wasting conditions. In addition, it is imperative that more than one
      endpoint be selected to be assured that there is concordance in the findings.
      However, prior to the selection of any endpoint measure, the investigators
      involved must be fully cognizant of the potential pitfalls and errors that can
      occur in every one of the selected methodologies. In anticipating these potential
      problems, developing strategies for the interpretation of the data is critical at
      the outset of any interventional management strategy. The manufacturers, the
      regulators and the investigators involved in the interventional management of
      chronic and acute wasting disorders must agree on the endpoints to be used and
      these endpoints must provide the most appropriate and valid information.
      Selection of nutritional and metabolic endpoints must be in part dependent on the
      disease process involved, the potential magnitude of the interventional effect
      and must be utilized in the context of a carefully designed experimental protocol
      with a well focused question(s).

PMID- 9915915
TI  - Dimensions of "Functional Status" in trials or wasting.

PMID- 9915916
TI  - The impact of AIDS-associated wasting on quality of life: qualitative issues of
      measurement and evaluation.

PMID- 9915917
TI  - Dietary treatment in secondary wasting and cachexia.

PMID- 9915918
TI  - Perspectives on exercise and wasting.
AB  - Recommendations for endpoints in clinical trials of wasting that involve exercise
      should involve selection that clearly identifies the effects of exercise. Broad
      endpoints such as morbidity and mortality must be corrected for the effects of
      age, smoking, hypertension, etc. in order to gain adjusted information pertinent
      to exercise. Selection of variables related to physiological function although
      more specific i.e., maximal oxygen uptake, must still be viewed from the
      perspective that other variables may contribute to the values measured.
      Nevertheless, physiological information obtained from performance tests may well
      provide useful endpoints. In this regard, V02 max, heartrate and pulmonary
      ventilation at fixed work loads, muscular strength, reaction time, flexibility,
      blood gases, cardiac output, stroke volume, serum lactate, and properties of
      skeletal muscle such as mitochondria concentration and components related to
      muscle energetics, e.g., adenosine triphosphate. In addition exercise will
      definitely impact body mass and composition as well as configuration. The latter
      is assessable through utilization of somatogramography. Analysis of muscle
      depends on muscle biopsy and magnetic resonance spectroscopy. Neither of these
      methods has been employed in clinical trials to the best of our knowledge. Thus,
      one needs evidence that exercise in the clinical trial provides a discrete effect
      on performance capabilities, body status and biologically important variables.

PMID- 9915919
TI  - Approved pharmacologic interventions for wasting: an overview and lessons
      learned.

PMID- 9915920
TI  - Working group session report: cancer.

PMID- 9915921
TI  - Working group session report: wasting in geriatrics and special consideration in
      design of trials involving the elderly subjects.

PMID- 9915922
TI  - Working group session report: HIV/AIDS working group.

PMID- 9915923
TI  - Working group session report: chronic renal and gastrointestinal disease.

PMID- 9915924
TI  - Working group session report: special considerations in trials involving
      children.

PMID- 9915925
TI  - Summary remarks.

PMID- 9915926
TI  - Effects of age on activity patterns after coronary artery bypass surgery.
AB  - OBJECTIVE: To examine the effect of age on activity patterns, including circadian
      rhythms and levels, after coronary artery bypass surgery (CABS). DESIGN: Repeated
      measures, correlational. SETTING: Northeastern university-affiliated tertiary
      coronary care center. SUBJECTS: Eight middle-aged (mean age = 57 years) and 14
      older (mean age = 72 years) adults who had undergone first, isolated CABS.
      OUTCOME MEASURES: Wrist actigraph measures of levels (daytime activity) and
      circadian patterns of activity (acrophase, amplitude, percent rhythm, mesor),
      self-reported postoperative clinical activity milestones, and Sickness Impact
      Profile subscales of ambulation dysfunction and sleep-rest. INTERVENTION:
      Measurement of activity over postoperative days 2 through 5, including wrist
      actigraphy, Sickness Impact Profile ambulation and sleep-rest subscales, and
      daily clinical activity milestones. RESULTS: Repeated measures ANOVA was used in
      the data analysis. Statistically significant increases were found in percent
      rhythm (P <.001), amplitude (P <.001), activity level (P <.001), and clinical
      activity milestones (P <.001) over postoperative days 2 through 5. Significant
      effects of age were found on amplitude (P =.02) and percent rhythm (P =.008).
      Significant age-by-time effects were found for circadian amplitude (P =.03) and
      percent rhythm (P =.02). There was a nonstatistically significant (P =.07) age by
      time interaction effect on daytime activity. Trends in amplitude, percent rhythm,
      and daytime activity indicated that these activity parameters increased more
      slowly in older adults, compared with middle-aged adults, after initially similar
      levels on postoperative days 2 and 3. CONCLUSION: Both middle-aged and older
      adults increase daily activity and the strength of circadian activity pattern
      over days 2 through 5. However, these variables increase more rapidly in middle
      aged adults after essentially identical levels on postoperative days 2 and 3.

PMID- 9915927
TI  - Video-assisted thoracic surgery (VATS).

PMID- 9915928
TI  - Gender differences in fears related to coronary arteriography.
AB  - OBJECTIVE: To compare levels of fear and the intensity of specific fears in women
      and men related to coronary arteriography (CA). DESIGN: Prospective survey.
      SETTING: A 1360-bed university hospital. Data were collected before, during, and
      after CA, and again 6 months later. SUBJECTS: The sample consisted of 54 women
      and 166 men undergoing scheduled CA. METHODS: To compare fear levels at different
      points of evaluation; two analyses of covariance for repeated measures were
      performed. RESULTS: On average, women had significantly higher mean scores of
      fear across the points of evaluation on the Visual Analogue Scale than men (P
      <.001). During the hospital stay, the most intense fear for both women and men
      was the fear of coronary artery bypass grafting and the uncertainty about the
      illness, whereas at home it was the fear of myocardial infarction. On average,
      women reported significantly intense fears more frequently than men across time.
      On average, men experienced more intensive fear of problems in their sex life
      than women (P =. 032). The changes in intensity of fears over time were not
      significantly different by gender, except in fear of pain (P =.013), health care
      staff not having enough time to care for the patient (P =.039), and health care
      staff discussing the patient's condition without the patient being present (P
      =.048). Age and prior CA were found to be significantly related to most of the
      fears at different points of evaluation, and to the changes of fears over time.
      CONCLUSION: There existed differences in the tendency to report intensity of
      fears by gender; however, the intensity of fears changed in a similar way over
      time. The results suggest that the few gender differences in fears that existed
      may be explained by the treatment chosen for the patients and the patients'
      acceptance of it. Therefore, it is important to adapt information and support
      according to the treatment chosen for the patient.

PMID- 9915929
TI  - Perceived learning needs of patients with heart failure.
AB  - OBJECTIVE: To determine the perceived learning needs of patients with heart
      failure (HF) compared with identified needs by registered nurses (RNs). DESIGN:
      Descriptive, comparative. SETTING: Two midwestern hospitals: 1 community hospital
      and 1 that is part of a large, university-affiliated, integrated health care
      system. SAMPLE: A convenience sample of 84 adult patients with HF from left
      ventricular systolic dysfunction and 84 registered nurses. OUTCOME MEASURE: The
      Heart Failure Learning Needs Inventory, developed for this study, was used to
      rate 98 individual items divided into 8 subscales suggested in the Agency for
      Health Care Policy and Research (AHCPR) practice guidelines. The subscales
      include general HF information, psychologic adaptation to illness, risk factors,
      medications, diet, activity, prognosis, and signs and symptoms. RESULTS:
      Multivariate analysis of variance was completed. The patients perceived the
      subscales of general HF information, risk factors, medications, prognosis, and
      signs and symptoms as more important to learn than the RNs did (P <.05). Patients
      perceived diet information as less important to learn than the RNs did (P <. 05).
      There were no differences in the patients' and nurses' perceptions in the
      activity and psychologic subscales. The patients perceived all 8 subscales as
      more realistic to learn than the RNs did (P <.05). Although not in identical
      order, both groups ranked education related to medication and signs and symptoms
      as the 2 priority areas. Diet information was ranked eighth by the patients and
      third by the RNs. CONCLUSION: The findings are consistent with previous research
      supporting the overall trend that patients with HF perceived patient education to
      be more important and realistic to learn during hospitalization than the nurses
      did. Patients and nurses identified education related to signs and symptoms and
      medication as the 2 most important content areas. In comparison with the AHCPR
      clinical practice guidelines, the group of RNs studied would ascribe the
      additional category of signs and symptoms as essential content to be taught
      during hospitalization.

PMID- 9915930
TI  - Comparisons of American-Chinese and Taiwanese patients' perceptions of dyspnea
      and helpful nursing actions during the intensive care unit transition from
      cardiac surgery.
AB  - OBJECTIVE: To compare perceptions by American-Chinese and Taiwanese patients who
      received ventilatory assistance of acute episodes of dyspnea and the related
      helpful nursing actions in the intensive care unit (ICU) after cardiac surgery.
      DESIGN: A descriptive qualitative design. SETTING: Two medical hospitals in
      northern California and Taiwan. PATIENTS: A purposive sample consisting of 30
      adult Chinese patients who experienced acute episodes of dyspnea while receiving
      assistance from a volume-cycled ventilator following cardiac surgery in the ICU
      from one study site in the United States (n = 10) and one study site in Taiwan (n
      = 20). OUTCOME MEASURES: The perceptions, natures, helpful nursing actions, and
      conceptual definition of the acute episode of dyspnea from the patients'
      perspective. INTERVENTION: Data were gathered through semi-structured interviews
      and analyzed by qualitative content analysis. RESULTS: All American-Chinese and
      Taiwanese subjects experienced physical discomforts, including tightness and
      congestion in the chest, labored breathing, sweating, palpitations, pain, and
      loss of vitality. Seventy percent of American-Chinese subjects and 90% of
      Taiwanese subjects reported having a mortal fear of death during and after the
      acute episode of dyspnea. The nature of the patients' perceptions of dyspnea
      revealed in this study can be categorized as unpredictability, sequence,
      intercorrelation, and exhaustion. Data analysis shows that the acute dyspneic
      process includes the immediate, following, later, and final transitions. Helpful
      nursing actions were identified as comforting, companionship, allowing self
      concentration, and providing information. CONCLUSION: Both American-Chinese and
      Taiwanese patients' perceptions of acute episodes of dyspnea and helpful nursing
      actions were identified and compared. Finally, the conceptual definition of
      patients' perceptions of acute dyspnea and a conceptual framework for this
      phenomenon were further tentatively developed to depict and delineate this
      phenomenon.

PMID- 9915931
TI  - Evaluation of a nurse-delivered smoking cessation intervention for hospitalized
      patients with cardiac disease.
AB  - OBJECTIVE: To determine the effect of a nurse-delivered smoking cessation
      intervention for hospitalized smokers on smoking cessation rates and smoking
      cessation self-efficacy at 6 months after enrollment. DESIGN: A quasi
      experimental design was used; specifically, a nonequivalent control group design
      was implemented. SETTING: A 450-bed major teaching and research tertiary care
      hospital, serving patients from across the province of British Columbia, Canada.
      SUBJECTS: Smokers with a cardiac diagnosis (n = 102) who were admitted to 1 of 2
      inpatient cardiac units for medical or surgical treatment. OUTCOME MEASURES: Self
      reported smoking status and self-reported smoking cessation self-efficacy.
      INTERVENTION: Two structured, in-hospital contacts, followed by 3 months of
      telephone support. The interventions focused on problem-solving and reinforcing
      the patient's self-efficacy. RESULTS: Of the patients enrolled, 86 completed 6
      month follow-up questionnaires. When subjects who were lost to follow-up were
      assumed to be smokers, 46% of the intervention group, compared with 31% of the
      control group, were nonsmokers. When key variables were controlled, we found that
      those subjects in the control group were 3 times more likely to relapse and begin
      smoking than those who received the intervention. There were no significant
      differences in follow-up smoking cessation self-efficacy scores in the treatment
      and control groups. When background variables were controlled, self-efficacy
      related to positive/social situations and habit/addictive situations were noted
      to be significantly higher in the intervention group. CONCLUSION: The findings of
      this research are encouraging; they suggest that a nurse-delivered smoking
      cessation intervention improved the smoking cessation rate in patients with
      cardiac disease.

PMID- 9915932
TI  - Dyspnea in patients with chronic obstructive pulmonary disease: does dyspnea
      worsen longitudinally in the presence of declining lung function?
AB  - OBJECTIVE: To determine the direction and rate of change in the symptom of
      dyspnea in patients with chronic obstructive pulmonary disease (COPD) whose lung
      function has worsened over time. DESIGN: Secondary analysis of a longitudinal
      data set. SETTING: Outpatient clinic. PATIENTS: Thirty-four medically stable male
      subjects with chronic obstructive pulmonary disease studied for 5.3 +/- 3.5
      years, with a mean reduction in FEV1 over the period studied of 330.9 +/- 288.0
      mL. Subjects were 63.3 +/- 5.5 years of age at entry into the study. OUTCOME
      MEASURES: Dyspnea and functional status scores were obtained using the Pulmonary
      Functional Status and Dyspnea Questionnaire. RESULTS: There was no significant
      difference in reports of dyspnea from the beginning to the end of the study,
      despite significant reductions in lung function. Of all activities studied,
      dyspnea when raising arms overhead was the only activity showing a relationship
      to the slope of change in FEV1 %. CONCLUSION: These findings suggest that,
      although patients with chronic lung disease experience varying degrees of
      deterioration in lung function longitudinally, there is no evidence that they
      report worsening of dyspnea in tandem with these physiologic changes. In this
      study, patient ratings of dyspnea longitudinally were not directly linked to
      changes in lung impairment.

PMID- 9915933
TI  - Streptococcus pneumoniae septic arthritis and osteomyelitis in an HIV
      seropositive patient.
AB  - Streptococcus Pneumoniae infections are a common cause of bacteremia and
      community-acquired pneumonia in HIV-positive individuals. Bone and joint
      infections as a result of S. pneumoniae are extremely rare. We report the first
      case of S. pneumoniae septic arthritis and osteomyelitis in an HIV-positive adult
      patient. The patient was successfully treated with oral levofloxacin.

PMID- 9915934
TI  - Bigeminal tachycardia.

PMID- 9915935
TI  - Benefit of music therapy for our intensive care unit (ICU) patients.

PMID- 9915936
TI  - 1998 ASHG presidential address. Making genomic medicine a reality.

PMID- 9915938
TI  - When less is more: gene loss as an engine of evolutionary change.

PMID- 9915939
TI  - Concerted evolution: molecular mechanism and biological implications.

PMID- 9915941
TI  - Mice and the role of unequal recombination in gene-family evolution.

PMID- 9915940
TI  - The genomic record of Humankind's evolutionary roots.

PMID- 9915942
TI  - Multiple ATM-dependent pathways: an explanation for pleiotropy.

PMID- 9915943
TI  - Structure of the gene for congenital nephrotic syndrome of the finnish type
      (NPHS1) and characterization of mutations.
AB  - Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal
      recessive disorder that is caused by mutations in the recently discovered nephrin
      gene, NPHS1 (AF035835). The disease, which belongs to the Finnish disease
      heritage, exists predominantly in Finland, but many cases have been observed
      elsewhere in Europe and North America. The nephrin gene consists of 29 exons
      spanning 26 kb in the chromosomal region 19q13.1. In the present study, the
      genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were
      screened for the presence of mutations in the gene. A total of 32 novel
      mutations, including deletions; insertions; nonsense, missense, and splicing
      mutations; and two common polymorphisms were found. Only two Swedish and four
      Finnish patients had the typical Finnish mutations: a 2-bp deletion in exon 2
      (Finmajor) or a nonsense mutation in exon 26 (Finminor). In seven cases, no
      mutations were found in the coding region of the NPHS1 gene or in the immediate
      5'-flanking region. These patients may have mutations elsewhere in the promoter,
      in intron areas, or in a gene encoding another protein that interacts with
      nephrin.

PMID- 9915944
TI  - LINE-1 elements at the sites of molecular rearrangements in Alport syndrome
      diffuse leiomyomatosis.
AB  - Deletions encompassing the 5' termini of the paired type IV collagen genes COL4A5
      and COL4A6 on chromosome Xq22 give rise to Alport syndrome (AS) and associated
      diffuse leiomyomatosis (DL), a syndrome of disseminated smooth-muscle tumors
      involving the esophagus, large airways, and female reproductive tract. In this
      study, we report isolation and characterization of two deletion junctions. The
      first, in a patient described elsewhere, arose by a nonhomologous recombination
      event fusing a LINE-1 (L1) repetitive element in intron 1 of COL4A5 to intron 2
      of COL4A6, resulting in a 13.4-kb deletion. The second, in a previously
      undescribed family, arose by unequal homologous recombination between the same L1
      and a colinear L1 element in intron 2 of COL4A6, resulting in a>40-kb deletion.
      L1 elements have contributed to the emergence of this locus as a site of frequent
      recombinations by diverse mechanisms. These give rise to AS-DL by disruption of
      type IV collagen and perhaps other as yet unidentified genes, evidenced by
      deletions as small as 13.4 kb.

PMID- 9915945
TI  - Prader-Willi syndrome is caused by disruption of the SNRPN gene.
AB  - A Prader-Willi syndrome patient is described who has a de novo balanced
      translocation, (4;15)(q27;q11.2)pat, with breakpoints lying between SNRPN exons 2
      and 3. Parental-origin studies indicate that there is no uniparental disomy and
      no apparent deletion. This patient expresses ZNF127, SNRPN exons 1 and 2, IPW,
      and D15S227E (PAR1) but does not express either SNRPN exons 3 and 4 or D15S226E
      (PAR5), as assayed by reverse transcription-PCR, of peripheral blood cells.
      Methylation studies showed normal biparental patterns of inheritance of loci
      DN34/ZNF127, D15S63, and SNRPN exon 1. Results for this patient and that reported
      by Sun et al. support the contention that an intact genomic region and/or
      transcription of SNRPN exons 2 and 3 play a pivotal role in the manifestations of
      the major clinical phenotype in Prader-Willi syndrome.

PMID- 9915946
TI  - Spectrum of mutations in alpha-mannosidosis.
AB  - alpha-Mannosidosis is an autosomal recessive disorder caused by deficiency of
      lysosomal alpha-mannosidase (LAMAN). The resulting intracellular accumulation of
      mannose-containing oligosaccharides leads to mental retardation, hearing
      impairment, skeletal changes, and immunodeficiency. Recently, we reported the
      first alpha-mannosidosis-causing mutation affecting two Palestinian siblings. In
      the present study 21 novel mutations and four polymorphic amino acid positions
      were identified by the screening of 43 patients, from 39 families, mainly of
      European origin. Disease-causing mutations were identified in 72% of the alleles
      and included eight splicing, six missense, and three nonsense mutations, as well
      as two small insertions and two small deletions. In addition, Southern blot
      analysis indicated rearrangements in some alleles. Most mutations were private or
      occurred in two or three families, except for a missense mutation resulting in an
      R750W substitution. This mutation was found in 13 patients, from different
      European countries, and accounted for 21% of the disease alleles. Although there
      were clinical variations among the patients, no significant LAMAN activity could
      be detected in any of the fibroblast cultures. In addition, no correlation
      between the types of mutations and the clinical manifestations was evident.

PMID- 9915947
TI  - Recurrence of the T666M calcium channel CACNA1A gene mutation in familial
      hemiplegic migraine with progressive cerebellar ataxia.
AB  - Familial hemiplegic migraine (HM) is an autosomal dominant migraine with aura. In
      20% of HM families, HM is associated with a mild permanent cerebellar ataxia
      (PCA). The CACNA1A gene encoding the alpha1A subunit of P/Q-type voltage-gated
      calcium channels is involved in 50% of unselected HM families and in all families
      with HM/PCA. Four CACNA1A missense mutations have been identified in HM: two in
      pure HM and two in HM/PCA. Different CACNA1A mutations have been identified in
      other autosomal dominant conditions: mutations leading to a truncated protein in
      episodic ataxia type 2 (EA2), small expansions of a CAG trinucleotide in
      spinocerebellar ataxia type 6 and also in three families with EA2 features, and,
      finally, a missense mutation in a single family suffering from episodic ataxia
      and severe progressive PCA. We screened 16 families and 3 nonfamilial case
      patients affected by HM/PCA for specific CACNA1A mutations and found nine
      families and one nonfamilial case with the same T666M mutation, one new mutation
      (D715E) in one family, and no CAG repeat expansion. Both T666M and D715E
      substitutions were absent in 12 probands belonging to pure HM families whose
      disease appears to be linked to CACNA1A. Finally, haplotyping with neighboring
      markers suggested that T666M arose through recurrent mutational events. These
      data could indicate that the PCA observed in 20% of HM families results from
      specific pathophysiologic mechanisms.

PMID- 9915948
TI  - Peroxisomal bifunctional protein deficiency revisited: resolution of its true
      enzymatic and molecular basis.
AB  - In the past few years, many patients have been described who have a defect of
      unknown origin in the peroxisomal beta-oxidation pathway. Complementation
      analysis has been done by various groups to establish the extent of the genetic
      heterogeneity among the patients. These studies were based on the use of two
      established cell lines, one with a deficiency of acyl-CoA oxidase and one with a
      deficiency of l-bifunctional protein (l-BP), and they showed that most patients
      belong to the l-BP-deficient group. However, molecular analysis of the cDNA
      encoding l-BP in patients failed to show any mutations. The recent identification
      of a new d-specific bifunctional protein (d-BP) prompted us to reinvestigate the
      original patient with presumed l-BP deficiency. In a collaborative effort, we
      have now found that the true defect in this patient is at the level of the d-BP
      and not at the level of the l-BP. Our results suggest that most, if not all,
      patients whose condition has been diagnosed as l-BP are, in fact, d-BP deficient.
      We tested this hypothesis in nine patients whose condition was diagnosed as l-BP
      deficiency on the basis of complementation analysis and found clear-cut mutations
      in the d-BP cDNA from all patients.

PMID- 9915949
TI  - Rhmod syndrome: a family study of the translation-initiator mutation in the Rh50
      glycoprotein gene.
AB  - Rhmod syndrome is a rare genetic disorder thought to result from mutations at a
      "modifier" but not at the suppressor underlying the regulator type of Rhnull
      disease. We studied this disorder in a Jewish family with a consanguineous
      background and analyzed RH and RHAG, the two loci that control Rh-antigen
      expression and Rh-complex assembly. Despite the presence of a d (D-negative)
      haplotype, no other gross alteration was found at RH, and cDNA sequencing showed
      a normal structure for D, Ce, and ce Rh transcripts in family members. However,
      analysis of RHAG transcript, which encodes Rh50 glycoprotein, identified a single
      G-->T transversion in the initiation codon, causing a missense amino acid change
      (ATG[Met]-->ATT[Ile]). This point mutation also occurred in the genomic region
      spanning exon 1 of RHAG, and its genotypic status in the mother and two children
      was confirmed by analysis of single-strand conformation polymorphism. Although
      blood typing showed a very weak expression of Rh antigens, immunoblotting barely
      detected the Rh proteins in the Rhmod membrane. In vitro transcription-coupled
      translation assays showed that the initiator mutants of Rhmod-but not those of
      the wild type-could be translated from ATG codons downstream. Our findings point
      to incomplete penetrance of the Rhmod mutation, in the form of "leaky"
      translation, leading to some posttranslational defects affecting the structure,
      interaction, and processing of Rh50 glycoprotein.

PMID- 9915950
TI  - Williams syndrome: use of chromosomal microdeletions as a tool to dissect
      cognitive and physical phenotypes.
AB  - In Williams syndrome (WS), a deletion of approximately 1.5 Mb on one copy of
      chromosome 7 causes specific physical, cognitive, and behavioral abnormalities.
      Molecular dissection of the phenotype may be a route to identification of genes
      important in human cognition and behavior. Among the genes known to be deleted in
      WS are ELN (which encodes elastin), LIMK1 (which encodes a protein tyrosine
      kinase expressed in the developing brain), STX1A (which encodes a component of
      the synaptic apparatus), and FZD3. Study of patients with deletions or mutations
      confined to ELN showed that hemizygosity for elastin is responsible for the
      cardiological features of WS. LIMK1 and STX1A are good candidates for cognitive
      or behavioral aspects of WS. Here we describe genetic and psychometric testing of
      patients who have small deletions within the WS critical region. Our results
      suggest that neither LIMK1 hemizygosity (contrary to a previous report) nor STX1A
      hemizygosity is likely to contribute to any part of the WS phenotype, and they
      emphasize the importance of such patients for dissecting subtle but highly
      penetrant phenotypes.

PMID- 9915951
TI  - Assignment of the muscle-eye-brain disease gene to 1p32-p34 by linkage analysis
      and homozygosity mapping.
AB  - Muscle-eye-brain disease (MEB) is an autosomal recessive disease of unknown
      etiology characterized by severe mental retardation, ocular abnormalities,
      congenital muscular dystrophy, and a polymicrogyria-pachygyria-type neuronal
      migration disorder of the brain. A similar combination of muscle and brain
      involvement is also seen in Walker-Warburg syndrome (WWS) and Fukuyama congenital
      muscular dystrophy (FCMD). Whereas the gene underlying FCMD has been mapped and
      cloned, the genetic location of the WWS gene is still unknown. Here we report the
      assignment of the MEB gene to chromosome 1p32-p34 by linkage analysis and
      homozygosity mapping in eight families with 12 affected individuals. After a
      genomewide search for linkage in four affected sib pairs had pinpointed the
      assignment to 1p, the MEB locus was more precisely assigned to a 9-cM interval
      flanked by markers D1S200 proximally and D1S211 distally. Multipoint linkage
      analysis gave a maximum LOD score of 6.17 at locus D1S2677. These findings
      provide a starting point for the positional cloning of the disease gene, which
      may play an important role in muscle function and brain development. It also
      provides an opportunity to test other congenital muscular dystrophy phenotypes,
      in particular WWS, for linkage to the same locus.

PMID- 9915952
TI  - Refinement of the chromosome 5p locus for familial calcium pyrophosphate
      dihydrate deposition disease.
AB  - Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease
      of articular cartilage that is radiographically characterized by
      chondrocalcinosis due to the deposition of calcium-containing crystals in
      affected joints. We have documented the disease in an Argentinean kindred of
      northern Italian ancestry and in a French kindred from the Alsace region. Both
      families presented with a common phenotype including early age at onset and
      deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of
      affected joints. Affected family members were karyotypically normal. Linkage to
      the short arm of chromosome 5 was observed, consistent with a previous report of
      linkage of the CPPDD phenotype in a large British kindred to the 5p15 region.
      However, recombinants in the Argentinean kindred have enabled us to designate a
      region<1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.

PMID- 9915953
TI  - A quantitative-trait locus on chromosome 6p influences different aspects of
      developmental dyslexia.
AB  - Recent application of nonparametric-linkage analysis to reading disability has
      implicated a putative quantitative-trait locus (QTL) on the short arm of
      chromosome 6. In the present study, we use QTL methods to evaluate linkage to the
      6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear families that were
      selected on the basis of a dyslexic proband. We have assessed linkage directly
      for several quantitative measures that should correlate with different components
      of the phenotype, rather than using a single composite measure or employing
      categorical definitions of subtypes. Our measures include the traditional
      IQ/reading discrepancy score, as well as tests of word recognition, irregular
      word reading, and nonword reading. Pointwise analysis by means of sib-pair trait
      differences suggests the presence, in 6p21.3, of a QTL influencing multiple
      components of dyslexia, in particular the reading of irregular words (P=.0016)
      and nonwords (P=.0024). A complementary statistical approach involving estimation
      of variance components supports these findings (irregular words, P=.007;
      nonwords, P=.0004). Multipoint analyses place the QTL within the D6S422-D6S291
      interval, with a peak around markers D6S276 and D6S105 consistently identified by
      approaches based on trait differences (irregular words, P=.00035; nonwords,
      P=.0035) and variance components (irregular words, P=.007; nonwords, P=.0038).
      Our findings indicate that the QTL affects both phonological and orthographic
      skills and is not specific to phoneme awareness, as has been previously
      suggested. Further studies will be necessary to obtain a more precise
      localization of this QTL, which may lead to the isolation of one of the genes
      involved in developmental dyslexia.

PMID- 9915954
TI  - Quantitative-trait locus for specific language and reading deficits on chromosome
      6p.
AB  - Reading disability (RD), or dyslexia, is a complex cognitive disorder manifested
      by difficulties in learning to read, in otherwise normal individuals. Individuals
      with RD manifest deficits in several reading and language skills. Previous
      research has suggested the existence of a quantitative-trait locus (QTL) for RD
      on the short arm of chromosome 6. In the present study, RD subjects' performance
      in several measures of word recognition and component skills of orthographic
      coding, phonological decoding, and phoneme awareness were individually subjected
      to QTL analysis, with a new sample of 126 sib pairs, by means of a multipoint
      mapping method and eight informative DNA markers on chromosome 6 (D6S461, D6S276,
      D6S105, D6S306, D6S258, D6S439, D6S291, and D6S1019). The results indicate
      significant linkage across a distance of at least 5 cM for deficits in
      orthographic (LOD = 3.10) and phonological (LOD = 2.42) skills, confirming
      previous findings.

PMID- 9915955
TI  - Localization of a gene for familial hemophagocytic lymphohistiocytosis at
      chromosome 9q21.3-22 by homozygosity mapping.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL), also known as familial
      erythrophagocytic lymphohistiocytosis and familial histiocytic reticulosis, is a
      rare autosomal recessive disorder of early childhood characterized by excessive
      immune activation. Linkage of the disease gene to an approximately 7.8-cM region
      between markers D9S1867 and D9S1790 at 9q21.3-22 was identified by homozygosity
      mapping in four inbred FHL families of Pakistani descent with a combined maximum
      multipoint LOD score of 6.05. This is the first genetic locus to be described in
      FHL. However, homozygosity by descent across this interval could not be
      demonstrated in an additional affected kindred of Arab origin, whose maximum
      multipoint LOD score was -0.12. The combined sample revealed significant evidence
      for linkage to 9q markers (LOD score with heterogeneity, 5.00). Identification of
      the gene(s) involved in the pathogenesis of FHL will contribute to an
      understanding of the control of T-lymphocyte and macrophage activation, which is
      central to homeostasis in the immune system.

PMID- 9915956
TI  - Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence
      for heterogeneity.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive
      disorder characterized by the early onset of overwhelming activation of T
      lymphocytes and macrophages, invariably leading to death, in the absence of
      allogeneic bone marrow transplantation. Using genomewide genetic linkage
      analysis, we analyzed a group of 17 families with FHL and mapped a locus for FHL
      to the proximal region of the long arm of chromosome 10. Ten families showed no
      recombination with three tightly linked markers, D10S1650 (LOD score [Z]=6.99),
      D10S556 (Z=5.40), and D10S206 (Z=3.24), with a maximum multipoint LOD score of
      11.22 at the D10S1650 locus. Haplotype analysis of these 10 families allowed us
      to establish D10S206 and D10S1665 as the telomeric and the centromeric flanking
      markers, respectively. Heterogeneity analysis and haplotype inspection of the
      remaining families confirmed that in seven families FHL was not linked to the
      10q21-22 region, thus providing evidence for genetic heterogeneity of this
      condition.

PMID- 9915957
TI  - Hereditary isolated renal magnesium loss maps to chromosome 11q23.
AB  - Hypomagnesemia due to isolated renal magnesium loss has previously been
      demonstrated in two presumably unrelated Dutch families with autosomal dominant
      mode of inheritance. Patients with magnesium deficiency may suffer from tetany
      and convulsions, but the patients with hereditary renal magnesium wasting can
      also be clinically nonsymptomatic. In a genomewide linkage study, we first
      excluded a possible candidate region, on chromosome 9q, that encompasses the gene
      for intestinal hypomagnesemia with secondary hypocalcemia and, subsequently,
      found linkage to markers on chromosome 11q23. Detailed haplotype analyses
      identified a common haplotype segregating in both families, suggesting both their
      relationship through a common ancestor and the existence of a single,
      hypomagnesemia-causing mutation within them. The maximum two-point LOD score
      (Zmax) was found for marker D11S4127 (Zmax=6.41 at a recombination fraction of.
      00), whereas a multipoint analysis gave a Zmax of 8.24 between markers D11S4142
      and D11S4171. Key recombination events define a 5. 6-cM region between these two
      markers on chromosome 11q23. We conclude that this region encompasses a gene,
      involved in renal magnesium handling, that is mutated in our patients and is
      different from the gene involved in intestinal magnesium handling.

PMID- 9915958
TI  - Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to
      chromosome 19q13.
AB  - Calcium homeostasis by the kidneys and parathyroids is mediated by the calcium
      sensing receptor (CaSR), which is located on 3q21-q24 and belongs to family C of
      the superfamily of G-protein coupled receptors that includes those for
      metabotropic glutamate, certain pheromones, and gamma-amino butyric acid (GABA
      B). Inactivating CaSR mutations result in familial benign hypercalcemia (FBH), or
      familial hypocalciuric hypercalcemia (FHH), whereas activating mutations result
      in hypocalcemic hypercalciuria. However, not all FBH patients have CaSR
      mutations, which, together with the mapping of another FBH locus to 19p13.3,
      suggests that additional CaSRs or second messengers may be involved. These may be
      identified by positional cloning, and we therefore performed a genomewide search,
      using chromosome-specific sets of microsatellite polymorphisms, in an Oklahoma
      family with an FBH variant (FBHOk), for which linkage to 3q and 19p had been
      excluded. Linkage was established between FBHOk and eight chromosome 19q13 loci,
      with the highest LOD score, 6.67 (recombination fraction.00), obtained with
      D19S606. Recombinants further mapped FBHOk to a <12-cM interval flanked by
      D19S908 and D19S866. The calmodulin III gene is located within this interval, and
      DNA sequence analysis of the coding region, the 5' UTR, and part of the promoter
      region in an individual affected with FBHOk did not detect any abnormalities,
      thereby indicating that this gene is unlikely to be implicated in the etiology of
      FBHOk. This mapping of FBHOk to chromosome 19q13 will facilitate the
      identification of another CaSR or a mediator of calcium homeostasis.

PMID- 9915960
TI  - A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for
      a putative bipolar affective disorder locus.
AB  - Previously, we demonstrated evidence of linkage to bipolar affective disorder
      (BP) in a single large, multigenerational family with a LOD score of 3.41 at the
      PFKL locus on chromosome 21q22.3. Additional families showed little support for
      linkage to PFKL under homogeneity or heterogeneity, in that study. We have
      expanded on that analysis, with 31 microsatellite markers at an average marker
      spacing of </=2 cM, in the largest multigenerational BP pedigree series reported
      to date. A two-point heterogeneity (alpha=0.5) LOD score of 3.35 (P<.000156) was
      found at the D21S1260 locus, 5 cM proximal to PFKL. Polylocus analysis with a
      cluster of three neighboring markers was consistent with these results (PL-HetLOD
      = 3.25). In the design of this study, 373 individuals from 40 families (from a
      total set of 1,508 individuals in 57 families) were chosen, as a cost-effective
      approach to genotyping this large sample set. Linkage analyses were performed
      with an "affecteds-only" method. As such, our results are based solely on genetic
      information from affected individuals, without assumptions about the disease
      locus genotypes of the unaffecteds. Furthermore, for ease of comparison, this
      study was performed with the same approach as a 10-cM genome scan for BP loci,
      the results of which will be reported elsewhere.

PMID- 9915959
TI  - Genome scan for human obesity and linkage to markers in 20q13.
AB  - Obesity is a highly prevalent, multigenic trait that predicts increased morbidity
      and mortality. Here we report results from a genome scan based on 354 markers in
      513 members of 92 nuclear families ascertained through extreme obesity and normal
      body weight. The average marker interval was approximately 10 cM. We examined
      four correlated obesity phenotypes, including the body-mass index (BMI) (both as
      a quantitative trait and as a discrete trait with a threshold of BMI > or /=30
      kg/m2) and percentage of fat (both as a quantitative trait and as a discrete
      trait with a threshold of 40%) as assessed by bioelectrical impedance. In the
      initial stage of the genome scan, four markers in 20q gave positive evidence for
      linkage, which was consistent across most obesity phenotypes and analytic
      methods. After saturating 20q with additional markers (25 markers total) in an
      augmented sample of 713 members from 124 families, we found linkage to several
      markers in a region, 20q13, previously implicated in both human and animal
      studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P
      values (based on Monte Carlo simulations, which controlled for multiple testing)
      < or /=. 01 for single-point analysis. In addition, the parametric, affecteds
      only analysis for D20S476 yielded a LOD score of 3.06 (P=. 00009), and the
      affected-sib-pair test yielded a LOD score of 3.17 (P=.000067). Multipoint
      analyses further strengthened and localized these findings. This region includes
      several plausible candidate genes for obesity. Our results suggest that one or
      more genes affecting obesity are located in 20q13.

PMID- 9915961
TI  - Rapid clearance of fetal DNA from maternal plasma.
AB  - Fetal DNA has been detected in maternal plasma during pregnancy. We investigated
      the clearance of circulating fetal DNA after delivery, using quantitative PCR
      analysis of the sex-determining region Y gene as a marker for male fetuses. We
      analyzed plasma samples from 12 women 1-42 d after delivery of male babies and
      found that circulating fetal DNA was undetectable by day 1 after delivery. To
      obtain a higher time-resolution picture of fetal DNA clearance, we performed
      serial sampling of eight women, which indicated that most women (seven) had
      undetectable levels of circulating fetal DNA by 2 h postpartum. The mean half
      life for circulating fetal DNA was 16.3 min (range 4-30 min). Plasma nucleases
      were found to account for only part of the clearance of plasma fetal DNA. The
      rapid turnover of circulating DNA suggests that plasma DNA analysis may be less
      susceptible to false-positive results, which result from carryover from previous
      pregnancies, than is the detection of fetal cells in maternal blood; also, rapid
      turnover may be useful for the monitoring of feto-maternal events with rapid
      dynamics. These results also may have implications for the study of other types
      of nonhost DNA in plasma, such as circulating tumor-derived and graft-derived DNA
      in oncology and transplant patients, respectively.

PMID- 9915962
TI  - Inbreeding effects on fertility in humans: evidence for reproductive
      compensation.
AB  - The effects of inbreeding on prereproductive mortality have been demonstrated in
      many natural populations, including humans. However, little is known about the
      effects in inbred individuals who survive to adulthood. We have investigated the
      effects of inbreeding on fertility among inbred adult Hutterites and demonstrate
      significantly reduced fecundity among the most inbred Hutterite women, as
      evidenced by longer interbirth intervals (P=.024) and longer intervals to a
      recognized pregnancy (P=.010) but not by increased rates of fetal loss (P>.50).
      These data suggest the presence of recessive alleles that adversely affect
      fecundity among the population. In contrast, completed family sizes do not differ
      among the more and the less-inbred Hutterite women who were born after 1920,
      suggesting that reproductive compensation is occurring among the more-inbred and
      less-fecund women. This recent reproductive strategy would facilitate the
      maintenance of recessive alleles and contribute to an overall decline in
      fertility in the population.

PMID- 9915963
TI  - The emerging tree of West Eurasian mtDNAs: a synthesis of control-region
      sequences and RFLPs.
AB  - Variation in the human mitochondrial genome (mtDNA) is now routinely described
      and used to infer the histories of peoples, by means of one of two procedures,
      namely, the assaying of RFLPs throughout the genome and the sequencing of parts
      of the control region (CR). Using 95 samples from the Near East and northwest
      Caucasus, we present an analysis based on both systems, demonstrate their
      concordance, and, using additional available information, present the most
      refined phylogeny to date of west Eurasian mtDNA. We describe and apply a
      nomenclature for mtDNA clusters. Hypervariable nucleotides are identified, and
      the relative mutation rates of the two systems are evaluated. We point out where
      ambiguities remain. The identification of signature mutations for each cluster
      leads us to apply a hierarchical scheme for determining the cluster composition
      of a sample of Berber speakers, previously analyzed only for CR variation. We
      show that the main indigenous North African cluster is a sister group to the most
      ancient cluster of European mtDNAs, from which it diverged approximately 50,000
      years ago.

PMID- 9915964
TI  - Molecular genetic analysis of remains of a 2,000-year-old human population in
      China-and its relevance for the origin of the modern Japanese population.
AB  - We extracted DNA from the human remains excavated from the Yixi site (
      approximately 2,000 years before the present) in the Shandong peninsula of China
      and, through PCR amplification, determined nucleotide sequences of their
      mitochondrial D-loop regions. Nucleotide diversity of the ancient Yixi people was
      similar to those of modern populations. Modern humans in Asia and the circum
      Pacific region are divided into six radiation groups, on the basis of the
      phylogenetic network constructed by means of 414 mtDNA types from 1, 298
      individuals. We compared the ancient Yixi people with the modern Asian and the
      circum-Pacific populations, using two indices: frequency distribution of the
      radiation groups and genetic distances among populations. Both revealed that the
      closest genetic relatedness is between the ancient Yixi people and the modern
      Taiwan Han Chinese. The Yixi people show closer genetic affinity with Mongolians,
      mainland Japanese, and Koreans than with Ainu and Ryukyu Japanese and less
      genetic resemblance with Jomon people and Yayoi people, their predecessors and
      contemporaries, respectively, in ancient Japan.

PMID- 9915965
TI  - Combined linkage and association sib-pair analysis for quantitative traits.
AB  - An extension to current maximum-likelihood variance-components procedures for
      mapping quantitative-trait loci in sib pairs that allows a simultaneous test of
      allelic association is proposed. The method involves modeling of the allelic
      means for a test of association, with simultaneous modeling of the sib-pair
      covariance structure for a test of linkage. By partitioning of the mean effect of
      a locus into between- and within-sibship components, the method controls for
      spurious associations due to population stratification and admixture. The power
      and efficacy of the method are illustrated through simulation of various models
      of both real and spurious association.

PMID- 9915966
TI  - A simulation study of the effects of assignment of prior identity-by-descent
      probabilities to unselected sib pairs, in covariance-structure modeling of a
      quantitative-trait locus.
AB  - Sib pair-selection strategies, designed to identify the most informative sib
      pairs in order to detect a quantitative-trait locus (QTL), give rise to a missing
      data problem in genetic covariance-structure modeling of QTL effects. After
      selection, phenotypic data are available for all sibs, but marker data-and,
      consequently, the identity-by-descent (IBD) probabilities-are available only in
      selected sib pairs. One possible solution to this missing-data problem is to
      assign prior IBD probabilities (i.e., expected values) to the unselected sib
      pairs. The effect of this assignment in genetic covariance-structure modeling is
      investigated in the present paper. Two maximum-likelihood approaches to
      estimation are considered, the pi-hat approach and the IBD-mixture approach. In
      the simulations, sample size, selection criteria, QTL-increaser allele frequency,
      and gene action are manipulated. The results indicate that the assignment of
      prior IBD probabilities results in serious estimation bias in the pi-hat
      approach. Bias is also present in the IBD-mixture approach, although here the
      bias is generally much smaller. The null distribution of the log-likelihood ratio
      (i.e., in absence of any QTL effect) does not follow the expected null
      distribution in the pi-hat approach after selection. In the IBD-mixture approach,
      the null distribution does agree with expectation.

PMID- 9915968
TI  - The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer
      disease.

PMID- 9915967
TI  - Further evidence for the increased power of LOD scores compared with
      nonparametric methods.
AB  - In genetic analysis of diseases in which the underlying model is unknown, "model
      free" methods-such as affected sib pair (ASP) tests-are often preferred over LOD
      score methods, although LOD-score methods under the correct or even approximately
      correct model are more powerful than ASP tests. However, there might be
      circumstances in which nonparametric methods will outperform LOD-score methods.
      Recently, Dizier et al. reported that, in some complex two-locus (2L) models, LOD
      score methods with segregation analysis-derived parameters had less power to
      detect linkage than ASP tests. We investigated whether these particular models,
      in fact, represent a situation that ASP tests are more powerful than LOD scores.
      We simulated data according to the parameters specified by Dizier et al. and
      analyzed the data by using a (a) single locus (SL) LOD-score analysis performed
      twice, under a simple dominant and a recessive mode of inheritance (MOI), (b) ASP
      methods, and (c) nonparametric linkage (NPL) analysis. We show that SL analysis
      performed twice and corrected for the type I-error increase due to multiple
      testing yields almost as much linkage information as does an analysis under the
      correct 2L model and is more powerful than either the ASP method or the NPL
      method. We demonstrate that, even for complex genetic models, the most important
      condition for linkage analysis is that the assumed MOI at the disease locus being
      tested is approximately correct, not that the inheritance of the disease per se
      is correctly specified. In the analysis by Dizier et al., segregation analysis
      led to estimates of dominance parameters that were grossly misspecified for the
      locus tested in those models in which ASP tests appeared to be more powerful than
      LOD-score analyses.

PMID- 9915969
TI  - p53 variants predisposing to cancer are present in healthy centenarians.

PMID- 9915970
TI  - Maternally inherited cardiomyopathy: an atypical presentation of the mtDNA 12S
      rRNA gene A1555G mutation.

PMID- 9915971
TI  - An Alu-mediated 6-kb duplication in the BRCA1 gene: a new founder mutation?

PMID- 9915972
TI  - Cystic fibrosis mutations in heterozygous newborns with hypertrypsinemia and low
      sweat chloride.

PMID- 9915973
TI  - A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1)
      associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction.

PMID- 9915974
TI  - Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the
      digestive tract with mutation of the PTEN gene.

PMID- 9915975
TI  - Failure to detect linkage of preeclampsia to the region of the NOS3 locus on
      chromosome 7q.

PMID- 9915976
TI  - Exclusion of chromosome 7 for Kartagener syndrome but suggestion of linkage in
      families with other forms of primary ciliary dyskinesia.

PMID- 9915977
TI  - A new locus for nonsyndromic hereditary hearing impairment, DFNA17, maps to
      chromosome 22 and represents a gene for cochleosaccular degeneration.

PMID- 9915978
TI  - Two novel single-base-pair substitutions adjacent to the CAG repeat in the
      huntington disease gene (IT15): implications for diagnostic testing.

PMID- 9915979
TI  - The interpretation of the parameters in the transmission/disequilibrium test.

PMID- 9915980
TI  - Cancer genetics and insurance.

PMID- 9915982
TI  - Nuclear transfer in the rhesus monkey: practical and basic implications.
AB  - In early 1997, the birth of a lamb after transfer of the nucleus from an adult
      mammary gland cell into an enucleated oocyte, along with the production of rhesus
      monkeys by nuclear transfer of embryonic cells, marked a reemergence of the field
      of mammalian cloning. Clonally derived rhesus monkeys would be invaluable in
      biomedical research, and the commercial interests in transgenic sheep and cattle
      propagated by cloning are substantial. Nuclear transfer technology is under
      consideration in human in vitro fertilization clinics to overcome infertility
      secondary to advanced maternal age or mitochondrial-based genetic disease.
      Nuclear transfer involves preparing a cytoplast as a recipient cell, in most
      cases a mature metaphase II oocyte from which the chromosomes have been removed.
      A donor nucleus cell is then placed between the zona and the cytoplast, and
      fusion, as well as cytoplast activation, is initiated by electrical stimulation.
      Successful reprogramming of the donor cell nucleus by the cytoplast is critical-
      a step that may be influenced by cell cycle stage. Embryos produced by nuclear
      transfer are cultured in vitro for several cell divisions before cryopreservation
      or transfer to the oviduct or uterus of a host mother. The efficiency of
      producing live young by nuclear transfer in domestic species is low, with a high
      frequency of developmental abnormalities in both preterm and term animals.
      However, a number of pregnancies have now been established using fetal cells as
      the source of donor nuclei. The use of cell lines not only allows large clone
      sizes but also supports the ability to genetically manipulate cells in vitro
      before nuclear transfer. Ongoing research focused on the production of clonally
      derived rhesus monkeys using fetal fibroblasts and embryonic stem cells as the
      source of donor nuclei will be reviewed.

PMID- 9915983
TI  - Physiological perspectives on leptin as a regulator of reproduction: role in
      timing puberty.
AB  - How nutrition regulates reproductive activity remains a major unsolved question
      of reproductive biology. Reducing the level of nutrition during adulthood can
      lead to infertility, primarily through reduction of GnRH secretion. Inquiry about
      such a mechanism has its roots in the search for cues timing the onset of
      fertility, because the tempo of sexual maturation is much more closely associated
      with body growth than with chronological age. Growth depends on the quantity and
      quality of food intake. When food availability is low, small, short-lived species
      with high metabolism and reduced growth may not even attain puberty before they
      die. In longer-lived species, puberty is delayed for months or even years until
      more food becomes available. To appreciate fully how the pubertal progression is
      timed will require understanding how peripheral signals relating information
      about energy metabolism are sensed by the brain and how such information is
      routed through pathways controlling GnRH secretion. Here, we provide some
      background and physiologic perspective on the question of whether the fat-derived
      hormone leptin is the unique peripheral signal, is an important signal, is but
      one of a constellation of signals, or is not a signal timing puberty.

PMID- 9915984
TI  - Leptin's actions on the reproductive axis: perspectives and mechanisms.
AB  - Energy availability influences reproductive fitness. The activity of the
      reproductive axis is sensitive to the adequacy of nutrition and the stores of
      metabolic reserves. The adipocyte-derived hormone leptin is postulated to reflect
      the state of nutrition and energy reserves and serve as a metabolic gate to the
      reproductive system. Genetically obese ob/ob mice (lacking endogenous leptin) are
      infertile, and treatment of these animals with exogenous leptin stimulates the
      activity of the reproductive endocrine system and induces fertility in both
      sexes. Severely food-restricted animals have reduced circulating levels of
      leptin, which are associated with markedly reduced secretion of the
      gonadotropins, LH, and FSH. Treatment of food-restricted mice, rats, sheep, and
      monkeys with exogenous leptin reverses the diet-induced inhibition of
      gonadotropin secretion. Leptin has also been suggested to have a role in timing
      the onset of puberty in several species, although evidence that leptin is the
      primary metabolic signal for initiating the onset of puberty in any species is
      controversial. Notwithstanding this debate, it is undisputed for all species
      studied to date that adequate levels of leptin in the circulation are essential
      (but not sufficient) for pubertal progression and that leptin treatment can
      reverse the delay in sexual maturation caused by food restriction. Double-label
      in situ hybridization studies in the brain of the mouse, rat, and monkey have
      revealed that hypothalamic neurons expressing proopiomelanocortin and
      neuropeptide Y coexpress the leptin receptor, whereas no evidence has been
      adduced that GnRH neurons express this receptor. Together, these observations
      suggest that leptin is a metabolic signal to the neuroendocrine reproductive
      system and that under conditions of inadequate energy reserves, low leptin levels
      act as a metabolic "gate" to inhibit the activity of the neuroendocrine
      reproductive axis in both sexes.

PMID- 9915985
TI  - From the decidual cell internet: trophoblast-recognizing T cells.
AB  - The mammalian fetus has been perceived, paradoxically, as a successful allograft,
      a successful tumor, and a successful parasite. Success depends on fetal
      trophoblast cells, which form the interface with the mother. The maternal immune
      system is involved in the success of pregnancy and in its failure. The discovery
      that maternal gammadelta T cells may recognize and react to the fetal trophoblast
      and the definition of a vascular mechanism whereby their Th1 and Th2/3-type
      cytokines may abort embryos replaces confusion and debate with a new and simple
      clarity that enables further research.

PMID- 9915986
TI  - Dual function of 11beta-hydroxysteroid dehydrogenase in placenta: modulating
      placental glucocorticoid passage and local steroid action.
AB  - Target cell metabolism of glucocorticoids is now recognized as an important
      modulator of ligand access to the glucocorticoid receptor (GR). This metabolism
      occurs via two distinct 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes
      (types 1 and 2) that catalyze interconversion of active glucocorticoids (cortisol
      and corticosterone) and their inactive 11-keto products (cortisone and 11
      dehydrocorticosterone, respectively). The focus of this review is on the biology
      of the 11beta-HSD enzymes in the placenta, where they also regulate passage of
      maternal glucocorticoids to the fetus. The presence of this metabolic barrier at
      the maternal-fetal interface is potentially crucial to fetal growth and
      development, since maternal glucocorticoid levels are elevated in pregnancy and
      since excess glucocorticoid exposure in fetal life has detrimental effects on
      prenatal growth and increases susceptibility to disease in subsequent adult life.
      In primates, transplacental glucocorticoid passage also appears to play an
      important role in the induction of an autonomous fetal hypothalamic-pituitary
      adrenal axis near term. Placental 11beta-HSD is also likely to modulate
      glucocorticoid actions within the placenta, per se, by regulating their access to
      placental GR. Moreover, because some progesterone effects are exerted via the GR,
      placental 11beta-HSD may regulate progesterone-glucocorticoid competition for
      access to this receptor and thereby affect the biological actions of both
      steroids in the placenta.

PMID- 9915987
TI  - Identification and characterization of glycosylation-dependent cell adhesion
      molecule 1-like protein expression in the ovine uterus.
AB  - Glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1) is an endothelial
      glycoprotein secreted in lymph nodes that serves as a ligand for leukocyte cell
      surface selectin and mediates lymphocyte extravasation. In the present studies,
      rabbit anti-rat GlyCAM-1 IgG was used in immunochemical analyses of GlyCAM-1-like
      protein in the ovine uterus. In cyclic ewes, GlyCAM-1 expression increased in the
      endometrial luminal epithelium (LE) and shallow glandular epithelium (cGE)
      between Days 1 and 5 and then decreased between Days 11 and 15. In pregnant ewes,
      GlyCAM-1 in the LE and cGE was low on Days 11 and 13, increased on Day 15, and
      was abundant on Days 17 and 19. Immunoreactive GlyCAM-1 was also detected in the
      conceptus trophectoderm on Days 13-19. Staining for GlyCAM-1 in the smooth muscle
      of the vasculature and myometrium was constitutive, and no staining was detected
      in the stroma. An immunoreactive protein of approximately 45 kDa was identified
      in endometrial extracts and uterine flushings from cyclic and pregnant ewes. In
      pregnant ewes, the relative amount of immunoreactive GlyCAM-1 in uterine
      flushings was low on Days 11 and 13 but high on Days 15 and 17. Results suggest
      that a GlyCAM-1-like protein may be a secretory product of the endometrial
      epithelium and/or conceptus trophectoderm. Patterns of distribution observed for
      immunoreactive GlyCAM-1-like protein in the endometrial epithelium, combined with
      proposed functions for lymphoid GlyCAM-1, suggest that this mucin glycoprotein
      may be involved in conceptus-maternal interactions during the periimplantation
      period of pregnancy in sheep.

PMID- 9915988
TI  - Fertility impairment in granulocyte-macrophage colony-stimulating factor
      deficient mice.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been identified as
      a potentially important mediator of intercellular communication in the female
      reproductive tract, with principal target cells being the large populations of
      myeloid leukocytes in the cycling and pregnant uterus, the preimplantation
      embryo, and trophoblast cells of the developing placenta. To determine the
      physiological significance of this cytokine in reproduction, the fertility of
      genetically GM-CSF-deficient (GM-/-) mice was examined. Implantation rates were
      normal in GM-/- mice, and viable pups were produced. However, the mean litter
      sizes of GM-/- x GM-/- breeding pairs were 25% smaller at weaning than those of
      GM+/- x GM+/- pairs, due to fetal death late in gestation and early in postnatal
      life, with a disproportionate loss of male pups. On Day 17 of pregnancy, the mean
      number of resorbing and malformed fetuses was twice as high in pregnant GM-/-
      females (21%, vs. 11% in GM+/- females); the mean fetal weight and the mean
      fetal:placental ratio in surviving conceptuses were diminished by 7% and 6%,
      respectively; and the number of very small fetuses (< 500 mg) was 9-times as high
      (23% vs. 2.5%). Mortality during the first 3 wk of life was 4.5-times as high in
      pups born to GM-/- mothers (9%, vs. 2% in GM+/- females), and diminished size
      persisted in GM-/- pups, particularly males, into adulthood. The detrimental
      effect of maternal GM-CSF deficiency was less apparent when GM-/- females were
      mated with GM+/+ males; litter sizes at birth and at weaning were not
      significantly smaller than in GM+/- matings, and fetal weights and
      fetal:placental ratios were also comparable. When polymerase chain reaction was
      used to genotype embryonic tissue in heterozygote matings, GM-/- fetuses from GM
      /- females were found to be smaller than their GM+/- littermates and smaller than
      GM-/- fetuses gestated in GM+/- females. The size and distribution of uterine
      granulocyte and macrophage populations were normal during the estrous cycle,
      during early pregnancy, and in midgestation. Analysis of placental structure
      revealed that the ratio of labyrinthine to spongiotrophoblast areas was reduced
      by approximately 28% in GM-/- placentae, and the proportion of vacuolated
      trophoblast "glycogen cells" in the spongiotrophoblast layer was diminished.
      Compromised placental function as a result of subtle developmental aberrations
      may therefore partially account for embryonic growth retardation in GM-CSF
      deficient mice. Collectively, these studies show that fetal growth and viability
      are jeopardized in the absence of maternal GM-CSF. The detrimental effects are
      most clearly evident when the conceptus is also GM-CSF deficient, suggesting that
      GM-CSF of either maternal or fetal origin is required for optimal growth and
      survival of the fetus in mice.

PMID- 9915989
TI  - Acyl chain length-specific ceramide-induced changes in intracellular Ca2+
      concentration and progesterone production are not regulated by tumor necrosis
      factor alpha in hen granulosa cells.
AB  - Although tumor necrosis factor alpha (TNF-alpha) has long been known to be a
      potent inhibitor of gonadotropin-induced cytodifferentiation in the ovaries of a
      variety of mammalian species, its early signal transduction events are poorly
      understood. We previously demonstrated that TNF-alpha induces a small, delayed
      follicular stage-dependent increase in intracellular Ca2+ concentration ([Ca2+]i)
      in hen granulosa cells and promotes carbachol (Cch)-induced mobilization of Ca2+
      from intracellular stores in cells otherwise unresponsive to the cytokine. The
      focus of the current study was to examine the role of ceramide in TNF-alpha
      induced Ca2+ regulation. Treatment with exogenous sphingomyelinase (SMase; 50
      mU/ml) failed to influence basal [Ca2+]i but increased the magnitude of Cch
      induced Ca2+ transients. While C8-ceramide (0.03-30 microM), but not C2-ceramide
      (0.03-30 microM), mimicked this effect of SMase, challenge with sphingosine (3
      microM) resulted in a slow and delayed increase in basal [Ca2+]i. In order to
      determine whether SMase is activated by TNF-alpha action, changes in
      sphingomyelin and ceramide concentrations in F1 and F5,6 granulosa cells were
      determined. SMase activation was not observed after 1-, 5-, 15-, and 60-min
      incubations with TNF-alpha (1-50 ng/ml) in either F1 or F5,6 cells. Exogenous
      SMase and C2-ceramide both inhibited LH-induced progesterone production in F1 and
      F5,6 cells; however, incubation with C8-ceramide resulted in increases in both
      basal and LH-induced progesterone. In contrast, incubation with TNF-alpha had no
      effect on either basal or LH-induced steroidogenesis. In conclusion, our findings
      indicate that although ceramide regulates [Ca2+]i and progesterone secretion, the
      sphingolipid does not appear to play a role in the action of TNF-alpha in avian
      granulosa cells. Furthermore, ceramide-mediated responses are highly dependent on
      acyl chain length, potentially reflecting differences in the abilities of these
      ceramides to access, bind to, and/or activate ceramide-dependent signal
      transduction mechanisms. Nonetheless, since TNF-alpha did not increase the
      production of ceramide, the physiological regulator(s) of these responses remain
      unknown.

PMID- 9915990
TI  - Photoperiodic effects on gonadotropin-releasing hormone (GnRH) content and the
      GnRH-immunoreactive neuronal system of male Siberian hamsters.
AB  - Despite profound photoperiodic differences in circulating gonadotropin levels,
      consistent differences in the GnRH system have not been observed in Siberian
      hamsters (Phodopus sungorus) housed chronically in short or long days. During the
      transition from short to long days, however, male hamsters exhibit a transient
      increase in the number of cells expressing prepro-GnRH mRNA on the morning of the
      second long day. Here, we present two experiments designed to examine whether or
      not this change in mRNA level is associated with changes in GnRH protein
      synthesis. In the first experiment, we used RIA to measure GnRH content in
      preoptic area-mediobasal hypothalamic homogenates. We observed a significant
      increase in GnRH protein levels on the morning of the second long day relative to
      short- and long-day controls. The latter two groups did not differ from one
      another. In the second experiment, we used immunocytochemistry to quantify GnRH
      cell number in the various treatment groups. GnRH-immunoreactive (-ir) cell
      number did not increase significantly after long-day transfer relative to that in
      short-day controls; however, both of these groups had significantly more GnRH-ir
      neurons than long-day controls. We hypothesize that during the transition from
      short to long days, male Siberian hamsters experience a transient increase in
      GnRH production in a stable population of neurons. When GnRH secretion
      subsequently increases on long days, peptide content within neuronal cell bodies
      declines, leading to a decrease in the number of immunoreactive neurons detected.
      The rapid response of the hypothalamo-pituitary-gonadal axis in Siberian hamsters
      to a change in day length defines a narrow temporal window in which to identify
      the physiological, cellular, and molecular mechanisms mediating the photoperiodic
      regulation of reproduction.

PMID- 9915991
TI  - Noradrenaline stimulates the production of prostaglandin f2alpha in cultured
      bovine endometrial cells.
AB  - The stimulatory effect of noradrenaline (NA) as well as oxytocin (OT) on bovine
      endometrial prostaglandin (PG) F2alpha production, and the intracellular
      mechanisms of their actions, were investigated in cultured bovine endometrial
      cells (a mixture of epithelial, stromal, and glandular cells). The cells were
      cultured in Dulbecco's Modified Eagle's medium and Ham's F-12 medium (1:1 [v:v])
      with 10% calf serum. When the cells reached confluence, the culture medium was
      replaced with fresh medium with 0.1% BSA and various doses of NA (10(-8)-10(-4)
      M). NA stimulated PGF2alpha production in a dose-dependent manner (p < 0.05). To
      evaluate the intracellular mechanisms of NA and OT actions, the cells were
      treated with forskolin (an activator of adenylate cyclase), phorbol 12-myristate
      13-acetate (PMA, an activator of protein kinase [PK] C), Rp-cAMP (a competitive
      cAMP antagonist and an inhibitor of PKA), U-73122 (an inhibitor of phospholipase
      [PL] C), or anthranilic acid (ACA, an inhibitor of PLA2). Forskolin and PMA
      stimulated PGF2alpha production in a dose-dependent manner (p < 0.05). Rp-cAMP
      completely inhibited (p < 0.001) the NA-induced, but not the OT-induced,
      PGF2alpha production. Although U-73122 inhibited only OT-induced PGF2alpha
      production (p < 0.001), ACA completely stopped the actions of NA and OT. The
      overall results indicate that NA as well as OT is involved in the regulation of
      the endometrial PGF2alpha production in cattle and that the stimulatory effects
      of NA and OT on PGF2alpha production are mediated via the PKA and PKC pathways,
      respectively.

PMID- 9915992
TI  - Timing of mating, sperm dynamics, and ovulation in a wild population of agile
      Antechinus (Marsupialia: dasyuridae).
AB  - Timing of mating, sperm transport and storage, and ovulation were examined in a
      wild population of agile Antechinus (Marsupialia: Dasyuridae) in order to
      ascertain the validity of direct comparisons between captive and field-based
      mating studies in this species. Mating commenced in early August, and all females
      had ovulated by the 27th of the month. Fifty-five percent of the mated females
      caught that had not yet ovulated were captured on 19-20 August. This corresponded
      with a peak (67%) in the ovulation date determined for pregnant females.
      Approximately 25.9 x 10(3) spermatozoa per side were recovered from the
      reproductive tract of each mated female captured (range: 1.7 x 10(3)-75.5 x 10(3)
      spermatozoa per side). Spermatozoa were consistently found in greater numbers in
      the lower isthmus (19.7 x 10(3) +/- 19.9 x 10(3) spermatozoa per side) of the
      oviduct ( approximately 67% of all sperm found in the female tract; range 17-94%)
      than elsewhere in the reproductive tract. Few spermatozoa were found in the upper
      isthmus, and none were detected in the ampulla. Sperm number in the female
      reproductive tract supports the hypothesis that females will mate several times
      within the one estrus. At the conclusion of the rut, approximately 80.0 x 10(3)
      spermatozoa remained in each testis and approximately 630 x 10(3) spermatozoa in
      each epididymis. Most epididymal spermatozoa were restricted to the distal
      corpus/proximal cauda regions of the duct. This study shows that both field and
      laboratory reproductive data correlate well in the agile Antechinus and that
      successful breeding is indeed an exercise in reproductive brinkmanship.

PMID- 9915993
TI  - Progesterone maintains large rat granulosa cell viability indirectly by
      stimulating small granulosa cells to synthesize basic fibroblast growth factor.
AB  - Ovarian follicles are composed of small and large granulosa cells (GCs). Since
      progesterone (P4) inhibits large GCs from undergoing apoptosis, studies were
      designed to determine whether both sizes of GCs bind P4. These studies revealed
      that fluorescein isothiocyanate-BSA-P4 bound only to the surface membranes of
      small GCs. This binding was steroid-specific and inhibited by an antibody
      directed against the ligand-binding domain of the nuclear P4 receptor (PR). In
      addition, a cell-impermeable derivative of P4, BSA-conjugated P4, was as
      effective as P4 in preventing apoptosis. Quantitative in situ hybridization
      studies showed that P4 increased the relative amount of basic fibroblast growth
      factor (bFGF) mRNA expressed per cell as well as the percentage of small GCs that
      expressed bFGF. To determine whether the anti-apoptotic action of P4 was mediated
      by bFGF, GCs were cultured in control medium supplemented with either P4, a
      neutralizing antibody to bFGF, or both P4 and the bFGF antibody. The results from
      this study demonstrated that P4 suppressed apoptosis and that this effect was
      attenuated in presence of the bFGF antibody. Basic FGF also prevented GC
      apoptosis, and its action was not influenced by either the PR antagonist (RU
      486), an inhibitor of P4 synthesis (aminoglutethimide), or a PR antibody.
      Finally, FGF receptors were detected on both small and large GCs. Collectively,
      these data support the hypothesis that P4 acts through a putative membrane
      receptor on small GCs to stimulate the synthesis of bFGF. Basic FGF then
      activates its receptors within large GCs, and this initiates a signal
      transduction pathway that maintains large GC viability.

PMID- 9915994
TI  - Elevation of inducible nitric oxide synthase activity in human endometrium during
      menstruation.
AB  - Nitric oxide (NO) is a known agonist of programmed cell death (apoptosis). In
      order to discover its potential role during menstrual shedding, a process
      associated with extensive apoptosis, we evaluated activity and mRNA levels of the
      inducible and constitutive isoforms of NO synthase (NOS) in endometrial specimens
      of the proliferative (n = 11), late-secretory (n = 7), and menstrual (n = 17)
      phase of the cycle. These levels were compared with the proportion of apoptotic
      cells by detection of histochemically labeled DNA fragments. Inducible NOS (iNOS)
      activity during menstruation was six times that of the proliferative or late
      secretory phase (p < 0.05), whereas constitutive NOS activity remained unchanged.
      Competitive reverse transcription-polymerase chain reaction revealed 146% and 77%
      increases of iNOS mRNA expression in the late-secretory and menstrual phases,
      respectively, compared to the proliferative phase (p < 0.05), whereas
      constitutive NOS mRNA expression remained constant. Inducible NOS immunostaining
      was restricted to epithelial cells, whereas constitutive NOS immunostainig was
      confined to vascular endothelia. In addition, the proportion of apoptotic cells
      within the glands of late-secretory or menstrual endometrium was twice that of
      the proliferative phase (p < 0.05). We conclude that local production of NO is
      involved in the signal transduction mechanisms leading to endometrial breakdown
      during menstruation.

PMID- 9915995
TI  - Nucleic acid sequence of feline preprorelaxin and its localization within the
      feline placenta.
AB  - The cat placenta is known to secrete large amounts of relaxin. We employed
      uteroplacental tissue at approximately Day 35 of gestation to determine the
      nucleic acid sequence of feline preprorelaxin using reverse transcription- and
      rapid amplification of cDNA ends-polymerase chain reaction. Feline preprorelaxin
      cDNA was found to consist of 540 base pairs encoding a protein of 180 amino acids
      (aa). We identified a signal peptide of 25 aa, a B domain of 33 aa, a C domain of
      98 aa, and an A domain of 24 aa. The putative receptor binding region in the N'
      terminal part of the B domain contained one substitution from the classical
      GRELVR motif (L-->F). Feline preprorelaxin shared highest homology with porcine
      and equine preprorelaxin. Northern analysis revealed a specific 1-kilobase
      transcript present in total RNA of feline uteroplacental tissue but not of liver
      tissue. Nonradioactive in situ hybridization was used to localize relaxin mRNA,
      and immunohistochemistry was used to localize the relaxin hormone and
      cytokeratin, in tissues of the feto-maternal interface recovered from two queens
      at Day 35 of gestation. Specific hybridization signals for relaxin mRNA were
      exclusively detected in cells located in the lamellar placental labyrinth but
      were absent from other placental and nonplacental uterine parts. The cells
      expressing relaxin mRNA also displayed immunoreactivity for cytokeratin and were,
      therefore, identified as trophoblast cells. Immunoreactive relaxin colocalized in
      those placental areas expressing relaxin mRNA. Trophoblast cells located at the
      villous chorioallantoic tips invading the endometrium and extravillous
      trophoblast cells in the junctional placental zone were devoid of relaxin.

PMID- 9915997
TI  - Effect of oxytocin receptor and beta2-adrenoceptor blockade on myometrial
      oxytocin receptors in parturient rats.
AB  - It has been proposed that the rise in myometrial oxytocin receptor (OTR)
      concentrations at term triggers parturition. In the present study, we have shown
      that in vivo infusion of the beta2-adrenoceptor (beta2AR) antagonist ICI-118.551
      in late pregnant rats prevents the rise in myometrial OTR binding normally seen
      during delivery. A reduced contractile responsiveness of uterine strips isolated
      from rats in labor when challenged with oxytocin (OT) and a slight shortening of
      gestation accompanied this effect. OTR mRNA levels were, however, unaltered after
      the treatment, suggesting that the effect of beta2AR blockade on myometrial OTR
      was posttranscriptional or due to influences on extra-myometrial tissue. Infusion
      of the OTR antagonist atosiban down-regulated OTR binding sites in the parturient
      myometrium and resulted in an impaired contractile response to OT without
      affecting gestational length. OTR gene expression did not change, as seen from
      unchanged OTR mRNA values. Neither atosiban nor ICI-118.551 infusions alone
      changed fetal mortality. A significant increase in the incidence of fetal deaths
      was found, however, when rats were treated with a combination of atosiban and ICI
      118.551. This treatment also down-regulated myometrial OTR and weakened the
      contractile response to OT, but it did not change gestational length. We conclude
      that the timing and onset of a normal parturition as well as a favorable outcome
      seem to be independent of a rise in OTR. This fact cannot exclude the possibility
      that an increase in OTR is of importance in the genesis of preterm labor. We
      suggest that beta2 stimulation up-regulates OTR during delivery. This effect may
      partly be responsible for the tachyphylaxis seen after the use of beta2 agonists
      to control preterm labor. We further suggest that OTR stimulation up-regulates
      OTR during labor. The OTR down-regulation seen after atosiban treatment adds to
      the direct relaxing effect of atosiban on the myometrium. In view of this,
      atosiban may prove to be a more useful tocolytic than the traditionally used
      beta2 agonists.

PMID- 9915996
TI  - Defective induction of the transcription factor interferon-stimulated gene factor
      3 and interferon alpha insensitivity in human trophoblast cells.
AB  - During pregnancy, trophoblast cells of the placenta contact maternal immune cells
      and yet are protected from attack. One mechanism that may account for this is
      that trophoblasts show altered expression of major histocompatibility complex
      (MHC) antigens. The gene for human leukocyte antigen G (HLA-G), a nonclassical
      gene, is expressed at high levels in trophoblast. Unlike other MHC class I genes,
      the HLA-G gene lacks an interferon (IFN) response element. Moreover, we
      demonstrate here that IFN, which regulates classical MHC class I genes in other
      cell types, does not affect these genes in trophoblast, owing to inactivation of
      an IFNalpha signaling pathway. Trophoblast cells (JEG-3 and JAR) were found to be
      selectively refractory to IFN. Specifically, although IFNalpha induced the
      transcription factors STAT1, STAT2, and IFN regulatory factor-1, and a protective
      response against encephalomyocarditis virus, it failed to protect the cells from
      vesicular stomatitis virus, activate a transfected MHC class I gene promoter, and
      induce the transcription factor IFN-stimulated gene factor (ISGF)-3. The lack of
      ISGF3 DNA-binding activity apparently was due to diminished p48/ISGF3gamma
      subunit activity since ISGF3 DNA-binding activity and IFNalpha induction of MHC
      class I promoter activity were reconstituted by p48/ISGF3gamma supplementation.
      These data indicate that a specific IFN signaling pathway is inactive in JEG-3
      trophoblast cells because of altered activity of p48/ISGF3gamma, and they suggest
      IFN insensitivity as a mechanism that may help promote feto-placental survival.

PMID- 9915998
TI  - Expression of 11beta-hydroxysteroid dehydrogenase, glucocorticoid receptor, and
      mineralocorticoid receptor genes in rat ovary.
AB  - A new concept in reproductive endocrinology is that the status of the ovary as a
      glucocorticoid target organ alters with follicular development. Evidence for a
      physiological role of glucocorticoids in the regulation of ovarian
      folliculogenesis has been strengthened by the discovery that 11beta
      hydroxysteroid dehydrogenase (11betaHSD) mRNA expression in human granulosa cells
      is developmentally regulated. In this study, we quantified the pattern of
      expression and investigated the cellular location of 11betaHSD type 1
      (11betaHSD1), 11betaHSD type 2 (11betaHSD2), glucocorticoid receptor (GR), and
      mineralocorticoid receptor (MR) mRNAs during follicular maturation in rat ovary.
      Immature female rats received treatment with eCG to induce preovulatory
      follicular development or eCG followed by hCG to induce luteinization.
      11betaHSD1, 11betaHSD2, GR, and MR mRNAs were all detectable by ribonuclease
      protection assay in ovarian total RNA. Treatment with eCG alone caused an
      approximately 8-fold increase in the ovarian level of 11betaHSD1 mRNA, which rose
      to approximately 30-fold after additional treatment with hCG. Equine CG alone did
      not measurably affect the ovarian 11betaHSD2 mRNA level, but additional treatment
      with hCG reduced it to 34% of the control level. Expression of GR mRNA was
      unchanged by any gonadotropin treatment, while MR mRNA was down-regulated. A
      similar pattern of 11betaHSD1, 11betaHSD2, GR, and MR mRNA expression was
      observed in isolated granulosa cells. These results provide direct experimental
      evidence that 11betaHSD genes are gonadotropically regulated in the rat ovary,
      including granulosa cells, and are consistent with a shift in glucocorticoid
      metabolism from inactivation (due to oxidation by 11betaHSD2) to activation
      (reduction by 11betaHSD1) during hCG-induced granulosa cell luteinization.

PMID- 9915999
TI  - Developmental competence, after transfer to recipients, of porcine oocytes
      matured, fertilized, and cultured in vitro.
AB  - The objective of this study was to evaluate the developmental ability of early
      porcine embryos produced in vitro and transferred to recipient gilts. Porcine
      cumulus-oocyte complexes were matured in modified North Carolina State University
      37 solution for 44-46 h (in vitro maturation, IVM). In vitro fertilization (IVF)
      was performed with frozen-thawed epididymal spermatozoa. Inseminated oocytes were
      cultured in vitro (IVC) for 0, 24, or 48 h in modified NCSU-37 solution. Embryos
      were surgically transferred to the oviducts of recipients in which estrus had
      been synchronized with eCG and hCG. On the 29th day post-IVF, the uteri of some
      recipients were surgically examined for pregnancy; then pregnant females were
      hysterectomized in order to examine number and weight of the fetuses.
      Developmental rates to fetuses for IVM/IVF oocytes cultured for 24 and 48 h were
      significantly lower (p < 0.05, 1.7% and 2.0%, respectively) than that of IVM/IVF
      oocytes without IVC (6.7%). However, the weights of fetuses (1.0-1.2 g) did not
      differ among the experimental groups. The other recipients were examined for
      pregnancy using an ultrasound pregnancy detector, and pregnant females were
      allowed to go to term. Healthy piglets were delivered by some recipients to which
      embryos cultured for 0 or 24 h had been transferred; however, no farrow was
      obtained from embryos cultured for 48 h before the transfer. The results indicate
      that the viability of in vitro-produced porcine embryos is decreased by IVC after
      IVF; however, these embryos have competence to develop to term. An improved IVC
      system of porcine IVM/IVF oocytes is needed to generate advances in this field.

PMID- 9916000
TI  - Accumulation of cyclooxygenase-2 gene transcripts in uterine tissues of pregnant
      and parturient cows: stimulation by oxytocin.
AB  - Cyclooxygenase 1 and 2 (COX-1 and COX-2) mRNA were measured by ribonuclease
      protection assays in total RNA extracted from intercaruncular and caruncular
      endometrium, myometrium, cotyledons, and cervical mucosa of pregnant cows.
      Tissues were obtained at gestational ages of 150 days and 275 days and at term
      not in labor, at term in labor, and 6-12 h postpartum. Additionally, the effect
      of oxytocin (OT) on COX-2 expression was determined in intercaruncular
      endometrium of six third-trimester cows (between 230 and 270 days of pregnancy),
      three of which were injected with OT (200 IU) and three with saline 2 h before
      tissues were harvested. Prostaglandin F2alpha (PGF2alpha) metabolite was measured
      in plasma samples taken at 15-min intervals before and after the injections.
      Results showed that COX-2 mRNA was expressed in every type of tissue examined,
      although in different concentrations and beginning at different stages. Other
      than in seminal vesicular and prostate glands used as positive controls, low
      concentrations of COX-1 mRNA were detected only in myometrium and caruncles.
      Cotyledons had the highest concentration of COX-2 transcripts at all stages
      studied. Caruncles had about half the concentration of COX-2 transcripts that was
      seen in cotyledons, and on Day 150 even less. COX-2 mRNA expression in both
      tissues increased with advancing gestation, but there was no difference between
      samples from term-no-labor and term-in-labor cows. COX-2 mRNA concentrations in
      endometrium and myometrium were low; they varied randomly during pregnancy with
      no significant increase until postpartum, when COX-2 transcripts in endometrium
      had increased severalfold whereas those in myometrium were similar to values
      before parturition. Cervical mucosa expressed COX-2 mRNA weakly until term but
      had increased markedly at parturition. Injection of 200 IU of OT induced a
      substantial increase in endometrial COX-2 mRNA concentration within 2 h; this was
      associated with linearly increasing plasma concentrations of 13, 14-hydroxy-15
      keto-prostaglandin F2alpha, which were still rising at termination of the
      experiment. The results suggest that endogenous OT is a major factor in induction
      of COX-2 expression and PGF2alpha release at term and during parturition in cows.

PMID- 9916001
TI  - Superovulatory response of one ovary is related to the micro- and macroscopic
      population of follicles in the contralateral ovary of the Cow.
AB  - We hypothesized that the ovulatory response of one ovary to FSH would be related
      positively to the size of the primordial and growing pools of follicles in the
      other ovary. Nonlactating cows (n = 26) were unilaterally ovariectomized and 2
      days later were superovulated. The superovulatory response was classified as Low
      (< 5 corpora lutea [CL]), Medium (5-14 CL), or High (> 14 CL). Surface follicles
      on the ovary removed before superovulation were classified as small (1-3 mm),
      medium (3-7 mm), or large ( > 7 mm), and the ovary was then fixed and serially
      sectioned. Follicles </= 1 mm in diameter in 388 +/- 38 fields (2 x 2 mm) per cow
      were classified as primordial, primary, secondary, or tertiary. By
      classification, Suboptimal ovaries contained < 100 follicles </= 1 mm and Optimal
      ovaries contained > 250 follicles </= 1 mm. Number of CL was correlated
      positively with total number of primordial, tertiary, and medium surface
      follicles. Number of Empty fields (2 x 2-mm fields containing no follicles) was
      correlated negatively with superovulatory response and number of primordial
      follicles. Number of CL was related to number of tertiary follicles in a positive
      linear manner and the number of medium follicles in a positive quadratic manner
      (r 2 = 0.66). Numbers of primordial, tertiary, small surface follicles, medium
      surface follicles, and total surface follicles were lower (p </= 0.06) in the Low
      superovulatory response group than in the Medium or High group. Suboptimal
      ovaries had fewer small surface follicles and fewer CL than Optimal ovaries (p <
      0.05). We conclude that superovulatory response in cattle is related positively
      to the pools of primordial and growing follicles in the bovine ovary.

PMID- 9916002
TI  - Localization of leukemia inhibitory factor and its receptor in human placenta
      throughout pregnancy.
AB  - Mice in which the gene that encodes the receptor (R) for leukemia inhibitory
      factor (LIF) has been deleted show abnormal growth and development of the
      placenta. This indicates that LIF plays an important role in placental
      development. The expression of LIF-R and LIF was examined in human trophoblast
      and decidua using in situ hybridization and immunocytochemistry. LIF-R mRNA and
      immunoreactivity was localized in villous and extravillous trophoblast throughout
      pregnancy, and in endothelial cells of the fetal villi. Strong expression of mRNA
      encoding LIF was detected in decidual leukocytes, which are abundant at the
      implantation site. Extravillous trophoblast, which invades the maternal decidua,
      therefore expresses LIF-R as it moves past decidual leukocytes, which express LIF
      mRNA. The effect of LIF on cultured human trophoblast was examined in vitro.
      Recombinant human LIF had no effect on [3H]thymidine incorporation by purified
      extravillous trophoblast, nor on expression of integrins alpha1, alpha5, or beta1
      by isolated trophoblast. These results identify fetal endothelial cells and all
      cells of the trophoblast lineage as targets for the action of LIF in human
      placenta. Although its effects on trophoblast are not yet clear, LIF appears to
      mediate interactions between maternal decidual leukocytes and invading
      trophoblast. LIF may also play a critical role in controlling angiogenesis in the
      placental villi, since human fetal endothelial cells express LIF-R, and mice
      lacking a functional LIF receptor gene show altered vascular development in the
      placenta.

PMID- 9916003
TI  - Restricted expression of WT1 messenger ribonucleic acid in immature ovarian
      follicles: uniformity in mammalian and avian species and maintenance during
      reproductive senescence.
AB  - WT1 is a zinc finger protein with transcriptional repressor activity on several
      growth factor and growth factor receptor genes. In the ovary, a potential role
      for WT1 in the suppression of the development of immature follicles has been
      demonstrated. Here, gel retardation assays further showed that recombinant WT1
      protein interacted with consensus DNA sequences in the inhibin-alpha gene
      promoter. We investigated the pattern of WT1 expression in a wide variety of
      species and also over the reproductive life span in rats. In chicken ovaries,
      Northern blot analysis revealed the presence of WT1 transcript in small healthy
      white follicles (1-5 mm in diameter) and its absence in small yellow (6-12 mm in
      diameter) or larger follicles (F1-F5). In pig and monkey ovaries, WT1 expression
      was limited to granulosa cells of preantral follicles, as shown by in situ
      hybridization analysis. In rats, Northern blot analyses demonstrated the presence
      of WT1 transcript in the ovaries of young (3-mo-old) and middle-aged (9-mo-old)
      rats on the proestrous day, with a decrease in old (12-mo-old) rats in persistent
      estrus. In situ hybridization analysis further suggested that the decrease in WT1
      expression in aging ovaries was associated with fewer immature follicles. Thus,
      WT1 expression is restricted to immature follicles in diverse avian and mammalian
      species and over the reproductive life span in rats. These data demonstrated that
      WT1 is a marker for immature follicles and suggested a potential role of this
      transcriptional repressor in the slow growth of early follicles.

PMID- 9916004
TI  - Activation of an adenosine 3',5'-cyclic monophosphate-dependent Cl- conductance
      in response to neurohormonal stimuli in mouse endometrial epithelial cells: the
      role of cystic fibrosis transmembrane conductance regulator.
AB  - Previous studies have demonstrated that Cl- secretion by the mouse endometrial
      epithelium is under neurohormonal influence. The present study characterized the
      Cl- conductance activated by a number of agonists in the mouse endometrial
      epithelial cells using the whole-cell voltage-clamp technique. Adrenaline (1
      microM), prostaglandin (PG) E2 (5-10 microM), and PGF2alpha (100 microM)
      activated a whole-cell current that exhibited a linear I-V relationship as well
      as time- and voltage-independent characteristics. However, the current magnitude
      varied with different agonists. The agonist-activated current could be mimicked
      by an adenylate cyclase activator, forskolin (10 microM), and suppressed by an
      adenylate cyclase inhibitor, MDL12330A, suggesting the involvement of cAMP.
      Current characteristics remained the same after cation replacement, leaving Cl-
      as the major permeant ion species in the solutions. The reversal potential of the
      agonist-induced current was close to the equilibrium potential of Cl- in the
      presence of a Cl- gradient, indicating the activation of Cl- conductance. The
      agonist-induced current was inhibited by the Cl- channel blocker diphenylamine
      2,2'-dicarboxylic acid (DPC), but not by the Cl- channel blocker 4,4'
      diisothiocyanatostibene-2, 2'-disulfonic acid (DIDS). The anion selectivity
      sequence of the current was NO3->Br->Cl->I-. The observed electrophysiological
      properties of the agonist-induced Cl- conductance were consistent with those
      reported for the cystic fibrosis transmembrane conductance regulator (CFTR), a
      cAMP-activated Cl- channel expressed in many epithelia. The expression of CFTR in
      the mouse endometrial cells was also demonstrated by Western blot analysis. It
      appears that neurohormonal regulation of the uterine fluid in the mouse
      endometrium converges on the cAMP-activated Cl- channel, presumably CFTR.

PMID- 9916005
TI  - Molecular cloning of the ovine Growth/Differentiation factor-9 gene and
      expression of growth/differentiation factor-9 in ovine and bovine ovaries.
AB  - Recently a novel member of the transforming growth factor beta (TGFbeta)
      superfamily termed growth/differentiation factor-9 (GDF-9) was shown to be
      expressed in ovaries of mice and humans, and to be essential for normal
      follicular development beyond the primary (type 2) follicle stage in mice. In the
      present study, the gene for ovine GDF-9 was isolated and characterized, and
      expression of GDF-9 mRNA in ovaries of domestic ruminants was examined. The
      predicted amino acid sequence of ovine GDF-9 is 77% and 66% homologous to human
      and mouse GDF-9, respectively. Specific hybridization using homologous 35S
      antisense probes was restricted to oocytes. In contrast to similar studies in
      mice in which GDF-9 was first detected beginning at the primary (type 2) follicle
      stage, in ovine and bovine ovaries GDF-9 mRNA was expressed beginning at the
      primordial (type 1) follicle stage. The observed timing and pattern of GDF-9
      expression in oocytes of domestic ruminants is consistent with a role for GDF-9
      in the initiation and maintenance of folliculogenesis in these species, and
      supports the general concept that early stages of follicular growth and
      development are regulated by intraovarian factors.

PMID- 9916006
TI  - Lack of class I major histocompatibility antigens on trophoblast of
      periimplantation blastocysts and term placenta in the pig.
AB  - In this study, the pattern of expression of class I major histocompatibility
      (MHC) antigens and mRNA on periimplantation blastocysts and term placental tissue
      was determined for the pig. Class I MHC antigens could not be detected
      immunohistochemically either on extra-embryonic membranes or on the embryonic
      portion of Day 14, 16, 22, and 25 blastocysts. Nor could class I MHC antigens be
      detected on the outer trophoblast epithelium and inner endodermal surface of the
      chorioallantoic membrane or on the outer and inner surfaces of the amnion at
      term. However, MHC class I antigens were detected on the vascular mesoderm found
      in both the chorion and amnion at term, and in Day 25 extra-embryonic membranes.
      Uterine endometrial cells and tissues and maternal peripheral blood leukocytes
      stained strongly for class I MHC antigens. There was a large difference in the
      intensity of class I MHC mRNA signal, detected by Northern blot analysis, in
      embryo/fetus-derived tissues compared to that in maternal tissues. The embryos
      appeared to express even less class I MHC mRNA than did the extra-embryonic
      membranes. In addition, in situ hybridization of Day 16 blastocysts indicated
      class I MHC mRNA to be ubiquitously expressed at low levels in embryos and extra
      embryonic tissues compared to uterine endometrial tissue controls. Taken
      together, these results indicate that class I MHC antigens are either not
      expressed on the surface of the extra-embryonic/fetal membranes during gestation
      in the pig or are expressed at very low levels, and that specific mRNA is
      expressed at correspondingly low levels.

PMID- 9916007
TI  - Expression of messenger ribonucleic acid splice variants for vascular endothelial
      growth factor in the penis of adult rats and humans.
AB  - Erectile dysfunction is often associated with problems in vascular perfusion to
      the erectile components of the penis. In order to better understand the factors
      that control vascular formation and perfusion in the erectile tissues of the
      penis, we have begun to characterize the expression of vascular endothelial
      growth factor (VEGF) in penis tissues. VEGF is one of several polypeptides that
      have significant angiogenic activity in vitro and in vivo. Extensive
      characterization of the VEGF gene and its products has shown that several
      different mature mRNA transcripts exist, originating from alternative splicing of
      the basic VEGF transcript. These variant transcripts can encode peptides with
      different biological activities. Penile tissue was obtained from adult rats and
      from human patients undergoing penile prosthesis implantation. Analysis of the
      forms of VEGF transcripts was performed using a reverse transcription-polymerase
      chain reaction technique with primer pairs derived from the first and eighth exon
      of the VEGF gene. The expression levels of the various isoforms in the rat penis
      were then quantified using RNase protection assays. Four previously described
      splice variants of VEGF mRNA (VEGF 120, 144, 164, 188) were detected in rat and
      human penile tissues. In contrast to what is seen in the rat lung, where the most
      abundant form of VEGF mRNA is the 188 splice isoform, VEGF 164 is the most
      abundant transcript detected in the penis. Finally, sequence analysis of numerous
      VEGF cDNA clones obtained from the rat penis demonstrated the presence of a
      previously undescribed VEGF splice variant that could give rise to a protein of
      110 amino acid residues (VEGF 110, GenBank accession no. AF080594). In summary, a
      number of VEGF mRNA isoforms are expressed in the rat and human penis, with the
      splice variant encoding a 164-amino acid protein present in greatest abundance.
      This study is a prelude to attempts to genetically manipulate VEGF expression in
      the penis as a therapy for erectile dysfunction.

PMID- 9916008
TI  - Circulating concentrations of estradiol, luteinizing hormone, and follicle
      stimulating hormone during waves of ovarian follicular development in prepubertal
      cattle.
AB  - Objectives were to characterize changes in concentrations of LH, FSH, and
      estradiol-17beta (estradiol) in blood and populations of ovarian follicles of
      prepubertal cattle during waves of follicular development and to evaluate
      interactions between day after follicular aspiration and month prepuberty for
      these variables. During each month (month prepuberty), ovarian follicles of
      prepubertal cattle were aspirated to induce synchronous emergence of a wave of
      follicular development (day after follicular aspiration). Characteristics of
      ovarian follicular development and concentrations of hormones in blood were
      evaluated during the synchronous wave of follicular growth. Multiple regression
      was used to estimate hormonal variables and evaluate interactions for variables
      between day after follicular aspiration and month prepuberty. There were no
      interactions between day after follicular aspiration and month prepuberty for
      numbers of follicles </= 4 or > 5 mm or concentrations of LH, FSH, and estradiol.
      The pattern of change in these variables after follicular aspiration was,
      therefore, similar each month prepuberty. There were interactions between day
      after follicular aspiration and month prepuberty for frequency and amplitude of
      LH pulses and size of largest follicle. There were also endocrine changes that
      were related to follicular development after follicular aspiration throughout the
      peripubertal period.

PMID- 9916009
TI  - Testis-like steroidogenesis in the ovotestis of the European mole, Talpa
      europaea.
AB  - The female European mole (Talpa europaea) presents a vivid paradox in relation to
      our contemporary understanding of mammalian sexual differentiation. These animals
      are exceptional among female mammals in that they possess bilateral ovotestes.
      The ovotestis contains a morphologically normal ovarian component that develops
      during the spring breeding season and a histologically defined testicular region,
      the interstitial gland, which enlarges during autumn when the ovarian component
      decreases in size. In correlation with this unusual gonadal situation, the female
      mole displays a penile clitoris traversed by a urethral canal. Although the
      histology of the ovotestis is well documented and has recently been extended to
      an additional three species of the genus Talpa, there have been no clear
      indications of the physiological function, particularly androgen production, of
      the ovotestis in these female moles. This paper presents the first clear evidence
      of seasonal variation in plasma testosterone concentrations, which parallel the
      growth and regression of the "testicular" interstitial gland, in T. europaea.
      Plasma androstenedione did not show significant seasonal variation, but plasma
      testosterone (1.06 +/- 0.2 ng/ml) and gonadal testosterone concentration (1.57 +/
      0.65 microgram/mg protein) in females in autumn were significantly higher (p <
      0.02) than plasma (0.4 +/- 0.2 ng/ml) and gonadal (0.24 +/- 0.21 microgram/mg)
      concentrations in pregnant or immediately postpartum females in spring. Our data
      also reveal selective metabolic production of testosterone from radiolabeled
      steroid precursors (progesterone and androstenedione) by these ovarian
      interstitial tissues and male testes; estradiol is produced by ovarian tissue but
      not interstitial gland or testis.

PMID- 9916010
TI  - Expression of the steroidogenic acute regulatory protein and luteinizing hormone
      receptor and their regulation by tumor necrosis factor alpha in rat corpora
      lutea.
AB  - Expression of both mRNA and protein of the steroidogenic acute regulatory protein
      (StAR), in correlation with progesterone (P) production and LH receptor (LHR)
      mRNA expression, was studied in the corpora lutea (CL) of gonadotropin-induced
      pseudopregnant and pregnant rats at various stages of CL development. Immature
      female rats, 21-22 days old, were injected s.c. with 20 IU eCG to stimulate
      follicle growth and then with 20 IU hCG 48 h later to induce ovulation. The
      ovaries were removed at various stages of CL development; either CL were isolated
      and snap frozen for total RNA analysis, or whole ovaries were fixed in Bouin's
      fluid for paraffin sectioning. The results of in situ hybridization,
      immunohistochemistry, and Northern blotting showed that the increase in StAR mRNA
      and protein expression was well correlated with the increase in serum P
      concentration. StAR expression was restricted to the luteal cells or theca cells
      in antral follicles. Both StAR mRNA and protein in the CL of pseudopregnant rats
      increased steadily on Day 1 and Day 4, reached highest levels on Day 4, and then
      dropped sharply on Day 8 when luteolysis takes place. LHR mRNA content was high
      on Day 1 but dropped significantly on Day 2. LHR mRNA increased to high levels on
      Day 4 and 8 and then declined on Day 12. StAR mRNA and protein levels in the CL
      of pregnant rats were high during early luteal development (Day 2, 4), increased
      even further on Day 9, and decreased on Day 13 when luteolysis takes place. It is
      therefore suggested that the expression of StAR coincides well with the capacity
      of P production in the CL and that StAR expression can be used as a functional
      "marker" of CL development. To study the possible effect of cytokines on StAR
      expression, pseudopregnant rats on Day 5 were injected s.c. with 10 IU hCG plus
      20 microg prolactin (PRL), with or without 500 IU tumor necrosis factor alpha
      (TNFalpha) 30 min later. TNFalpha significantly inhibited hCG/PRL-induced StAR
      and LHR mRNA expression at 1 and 3 h post-TNFalpha. It is suggested that the
      luteolytic effect of TNFalpha may be mediated by its direct inhibition on StAR
      expression or by an indirect decrease in LHR expression.

PMID- 9916011
TI  - Expression of cell adhesion molecules in murine placentas and a placental cell
      line.
AB  - Integrins and vascular cell adhesion molecule-1 (VCAM-1) are required for normal
      placental development. In this study, integrin subunits alpha4, alphav, beta1,
      and beta3, and VCAM-1 were investigated for expression in uteroplacental units
      (gestation day [g.d.] 6 and 8) and placentas (g.d. 10, 12, 14, 16, and 18) of
      Swiss-Webster mice. All subunits and VCAM-1 mRNA (identified by reverse
      transcriptase polymerase chain reaction [RT-PCR]) and protein (detected by
      immunofluorescence) were present in all tissues throughout gestation. VCAM-1 was
      expressed strongly in the ectoplacental cone and trophoblast giant cells, alpha4
      was expressed strongly by trophoblast giant cells and moderately by
      spongiotrophoblast and labyrinthine trophoblast, and alphav was expressed more
      strongly in the spongiotrophoblast than in the labyrinthine zone. The beta1 was
      more strongly expressed in the labyrinthine than the spongiotrophoblast zone,
      while beta3 and VCAM-1 were essentially equal in the two zones. Trophoblast-like
      SM9-1 cells were positive for all of the adhesion molecules when tested by RT-PCR
      and immunocytochemistry. Adhesion molecule expression in SM9-1 cells was
      consistent with expression in the labyrinthine zone. Collectively, the results of
      this study demonstrate that murine placentas contain mRNA and protein for alpha4,
      alphav, beta1, beta3, and VCAM-1, and that expression is cell-specific. These
      results and the identification of an adhesion molecule-expressing trophoblastic
      cell line should facilitate future studies on the function of adhesion molecules
      in placental development.

PMID- 9916012
TI  - Spermicidal activity of oxovanadium(IV) complexes of 1, 10-phenanthroline, 2,2'
      bipyridyl, 5'-bromo-2'-hydroxyacetophenone and derivatives in humans.
AB  - We have recently reported that tetrahedral metallocene complexes containing
      vanadium(IV) (vanadocene) have potent spermicidal activity against human sperm.
      The spermicidal activity was dependent on vanadium(IV) as the central metal ion
      within the bis-cyclopentadienyl (Cp2)-metal complex, but the variation of diacido
      groups and/or replacement with bidentate ligands coordinated to the Cp2
      vanadium(IV) moiety also significantly modulated the spermicidal potency. To
      assess the structure-activity relationship between vanadocenes and other
      coordination complexes of vanadium(IV), a set of 11 oxovanadium(IV) complexes
      with different geometrical configurations were synthesized and evaluated for
      spermicidal activity by computer-assisted sperm analysis. These complexes
      included mono and bis ancillary ligands, 1,10-phenanthroline (phen): [VO(phen),
      VO(phen)2, VO(Me2-phen), VO(Me2-phen)2, VO(Cl-phen), and VO(Cl-phen)2]; 2,2'
      bipyridyl (bipy): [VO(bipy), VO(bipy)2, VO(Me2-bipy), and VO(Me2-bipy)2], linked
      via nitrogen atoms; and 5'-bromo-2'-hydroxyacetophenone (acph): [VO(Br,OH
      acph)2], linked via oxygen donor atoms. All 11 oxovanadium(IV) complexes elicited
      concentration-dependent spermicidal activity at micromolar concentrations (EC50
      values: 5.5-118 microM). The bis-phenanthroline complex of oxovanadium(IV), VO(Cl
      phen)2, was the most active, and the mono bipyridyl complex, VO(bipy), was the
      least active; the order of efficacy was VO(Cl-phen)2 > VO(phen)2 > VO(Br,OH
      acph)2 > VO(Me2-phen) > VO(bipy)2 > VO(phen) > VO(Cl-phen) > VO(Me2-phen)2 >
      VO(Me2-bipy)2 > VO(Me2-bipy) > VO(bipy). The neutral complex, VO(Br, OH-acph)2,
      induced rapid sperm immobilization (T1/2 = 38 sec). The sperm-immobilizing
      activity of mono- and bis-ligated oxovanadium(IV) complexes was irreversible,
      since the treated sperm underwent apoptosis, as determined by the flow cytometric
      quantitation of mitochondrial membrane potential, surface Annexin V binding
      assay, and in situ DNA nick-end labeling of sperm nuclei. The percentages of
      apoptotic sperm quantitated by the flow cytometric assay correlated well with the
      spermicidal potency of oxovanadium(IV) complexes. These results provide
      unprecedented evidence that the spermicidal and apoptosis-inducing activities of
      vanadium(IV) complexes are determined by the oxidation state of vanadium as well
      as their geometry. Because of its rapid and potent sperm-immobilizing activity,
      the bromo-hydroxyacetophenone complex, [VO(Br,OH-acph)2], may be useful as a
      contraceptive agent.

PMID- 9916013
TI  - Differential splicing and expression of the relaxin-like factor gene in
      reproductive tissues of the marmoset monkey (Callithrix jacchus).
AB  - The relaxin-like factor (RLF) is a novel member of the insulin/relaxin/insulin
      like growth factor family of growth factors and hormones that is expressed
      predominantly in the reproductive system, with highest expression in the Leydig
      cells of the testis. Using a combination of molecular and immunological
      techniques, we have characterized the structure and expression of the RLF gene
      from a primate model, the marmoset monkey, with the intention of comparing this
      with recent results on the closely related hormone relaxin in this species. As in
      other species, including the human, RLF gene products can be detected maximally
      in Leydig cells and in the follicular theca interna cells and corpora lutea of
      the ovary. Reverse transcription-polymerase chain reaction analysis confirmed
      this expression and showed that in the corpus luteum, testis, and epididymis, a
      second, alternative RLF gene transcript was present that is expressed at low
      levels and that appears to be derived by differential splicing of a novel exon.
      Analysis of genomic DNA from the marmoset showed that in this species, the single
      copy gene contains a longer intronic region separating the two exons described
      for the human. Alternative splicing introduces a novel exon 1A between exons 1
      and 2, which leads to an altered open reading frame, with a new stop codon, such
      that if translated, the novel transcript will encode a truncated polypeptide
      comprising a C-terminally extended B-domain.

PMID- 9916014
TI  - Osteopontin localization in the Holstein bull reproductive tract.
AB  - Previously we reported that the 55-kDa fertility-associated protein in Holstein
      bull seminal plasma (SP) is osteopontin (OPN). The objective of the present study
      was to localize OPN in tissues and fluids in the Holstein bull reproductive tract
      to determine its origin. Antisera generated against human recombinant OPN, as
      well as antiserum prepared against purified bovine seminal plasma OPN, reacted
      with protein in SP, accessory sex gland fluid, seminal vesicle fluid, ampullary
      fluid, and urine using one- and two-dimensional SDS-PAGE Western blot analysis.
      However, these antisera failed to detect OPN in cauda epididymal fluid or
      solubilized sperm membranes. Immunofluorescence histochemistry localized OPN in
      the lumen and epithelial cells of the seminal vesicle and ampulla, but not in
      tissues of testis, epididymis, prostate, and bulbourethral gland. OPN was not
      detected immunohistochemically in epididymal, ampullary, or ejaculated sperm
      treated with or without Triton X-100. We concluded that the primary sources of
      OPN in bull SP are the seminal vesicles and ampulla.

PMID- 9916015
TI  - Apoptosis in the rat spermatogenic epithelium following androgen withdrawal:
      changes in apoptosis-related genes.
AB  - Programmed cell death is an important regulatory event in spermatogenesis.
      However, the molecular events governing apoptosis have not been characterized.
      Using the Leydig cell-specific toxin ethane dimethanesulfonate (EDS) to withdraw
      androgen support, we have investigated the relationship between apoptosis and
      apoptosis-related genes. Adult male Sprague-Dawley rats were injected (i.p.) with
      100 mg/kg EDS and killed at times of androgen depletion 2, 5, and 8 days
      postinjection. A 24-fold increase in the apoptotic index 8 days after EDS
      administration was demonstrated in tissue sections by in situ end-labeling of
      fragmented DNA. Leydig cell death and androgen withdrawal were confirmed by the
      absence of 3beta-hydroxysteroid dehydrogenase in testes from animals treated with
      EDS for 2 days. After androgen withdrawal, there were no significant changes in
      the levels of clusterin, Bcl-xl, Bak, and Bad. However, the expression of Bcl-2
      and Bax was up-regulated at 8 days after EDS administration. The induction of Bax
      at this time suggests that it may play a role in germ cell apoptosis following
      androgen withdrawal. The concomitant elevation in Bcl-2 expression may represent
      a survival mechanism for the remaining germ cells. There was also a decline in
      the expression of Fas-L and Fas-R in the pachytene spermatocytes and spermatids.
      Fas-R was also present in Sertoli cells, although Fas-L staining was minimal. As
      the colocalization of Fas-L and Fas-R correlates with the germ cell types that
      die in response to androgen withdrawal, the potential exists for apoptosis in the
      rat spermatogenic epithelium to be regulated by the Fas pathway.

PMID- 9916016
TI  - Gelatinases A and B and tissue inhibitors of metalloproteinases 1, 2, and 3
      during in vivo and in vitro decidualization of rat endometrial stromal cells.
AB  - An important event during decidualization is the remodeling of the extracellular
      matrix, an event controlled by the balance of matrix metalloproteinases and
      tissue inhibitors of metalloproteinases (TIMPs). A putative regulator of
      decidualization is prostaglandin E2 (PGE2). The present study shows that
      endometrial mRNA levels for TIMPs 1, 2, and 3 were increased while gelatinase A
      levels remained unchanged and gelatinase B levels decreased during oil-induced
      decidualization. The production of TIMPs 1, 2, and 3 and gelatinases A and B
      during in vitro decidualization was examined, as was the role of PGE2 as a
      regulator. Ovariectomized rats were given a regimen of estrogen and progesterone,
      which sensitized their uteri for decidualization, at which time endometrial
      stromal cells were isolated and cultured in serum-free conditions for 72 h.
      Northern blot analyses indicated the presence of the mRNAs for TIMPs and
      gelatinases, while reverse zymography and zymography showed the presence of their
      proteins. PGE2 decreased mRNA levels for TIMP-1 and gelatinase A but had no
      effect on gelatinase B or TIMPs 2 and 3. Indomethacin had no effect on any of the
      transcripts. These data indicate that rat endometrial stromal cells undergoing
      decidualization in vitro secrete gelatinases and TIMPs, and suggest that PGE2 may
      play a role in regulating tissue remodeling during decidualization.

PMID- 9916017
TI  - Tumor necrosis factor alpha decreases the viability of mouse blastocysts in vitro
      and in vivo.
AB  - Mouse blastocysts were exposed for 24 h to various concentrations of recombinant
      mouse tumor necrosis factor alpha (TNFalpha) and observed for their capacity to
      implant in vitro on a fibronectin-coated substrate or to develop in vivo after
      their transfer into surrogate females. Compared with findings in control
      blastocysts, exposure to TNFalpha resulted in a significant reduction in the
      average number of cells in the inner cell mass (ICM) lineage. This effect was
      associated with a significant increase in the frequency of cells identified as
      engaged in apoptosis by means of the terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling technique. No difference was found in the
      incidence of nuclear fragmentation between control and TNFalpha-exposed
      blastocysts. When TNFalpha-pretreated blastocysts were allowed to implant in
      vitro, significantly fewer embryos were able to maintain a structured ICM cluster
      at the center of the trophectoderm outgrowth. Although no difference was found in
      the average surface area of the outgrowths, implants derived from TNFalpha
      treated blastocysts contained significantly fewer nuclei than implants from
      control embryos. After transfer into recipient mice, TNFalpha-pretreated
      blastocysts implanted at about the same rate as control embryos, but a
      significantly higher rate of resorption was found among fetuses after exposure to
      the cytokine. In addition, the weight of the surviving fetuses was significantly
      lower than for control fetuses. These data indicate that the impact of TNFalpha
      on blastocysts is specifically aimed at the ICM lineage and that TNFalpha
      decreases the ability of embryos to differentiate into fetuses after
      implantation.

PMID- 9916018
TI  - Changes in uterine expression of leukemia inhibitory factor during pregnancy in
      the Western spotted skunk.
AB  - Mutation of the leukemia inhibitory factor (LIF) gene results in reproductive
      failure in LIF -/- mice due to an inability to implant their blastocysts. This
      condition is reversed by infusion of LIF or by transferral of embryos to
      pseudopregnant, wild-type mice. This led us to hypothesize that embryonic
      diapause in the spotted skunk is due to insufficient uterine expression of LIF
      whereas resumption of development and implantation are associated with increased
      LIF expression. We also investigated the hormonal control of LIF expression.
      Uterine concentrations of LIF mRNA were determined by quantitative reverse
      transcription-polymerase chain reaction. Changes in cell-specific localization of
      LIF mRNA and protein were determined by in situ hybridization and
      immunocytochemistry. LIF mRNA was detected but was not abundant during embryonic
      diapause; it then increased when blastocysts resumed development and remained
      elevated prior to implantation. LIF mRNA and protein could not be localized in
      the uterus during embryonic diapause but were quite apparent in luminal and
      glandular epithelium during blastocyst activation. Prolactin, progesterone, and
      estradiol failed to increase uterine concentrations of LIF mRNA above those in
      ovariectomized controls. These data are consistent with the initial hypothesis
      and suggest that LIF may somehow be involved in preparing the uterus for
      implantation in the spotted skunk.

PMID- 9916019
TI  - Scimitar-horned oryx (Oryx dammah) spermatozoa are functionally competent in a
      heterologous bovine in vitro fertilization system after cryopreservation on dry
      ice, in a dry shipper, or over liquid nitrogen vapor.
AB  - A heterologous bovine in vitro fertilization (IVF) system was used to study the
      functional competence of scimitar-horned oryx spermatozoa after cryopreservation.
      Four sperm-freezing methods were compared after dilution of ejaculates from six
      oryx with an equine semen extender: 1) dry ice, 2) dry shipper one-step, 3) dry
      shipper two-step, and 4) liquid nitrogen vapor. Post-thaw sperm motility,
      longevity, and acrosomal status were assessed and zona pellucida penetration,
      fertilization, and embryo cleavage were evaluated after coincubation of thawed
      oryx spermatozoa with in vitro-matured domestic cow oocytes. Sperm motility index
      (SMI) decreased (p < 0.05) over a 6-h period, but a high percentage (>/= 65%) of
      spermatozoa contained intact acrosomes in all treatments. Despite differences in
      sperm motility among methods, oocyte penetration, fertilization, and embryo
      cleavage did not differ (p >/= 0.05). However, cleavage success was < 50% across
      all treatments. There were positive correlations (p < 0.05; r = 0.81-0.97)
      between sample SMI at 3 and 6 h and fertilization, penetration, and cleavage, but
      no correlations (p >/= 0.05) between SMI at 0 or 1 h and IVF success. This study
      demonstrates that compatible heterologous gamete interaction allows thorough
      assessment of post-thaw sperm function in an endangered antelope. Scimitar-horned
      oryx spermatozoa appear relatively tolerant of varied cryopreservation methods,
      and preserved samples exhibit adequate post-thaw function to warrant use for
      assisted reproduction.

PMID- 9916020
TI  - Relaxin secretion and gene expression in porcine granulosa and theca cells are
      stimulated during in vitro luteinization.
AB  - During formation of the corpus luteum, the primary source of relaxin switches
      from theca cells (TC) to granulosa-derived, large luteal cells. What controls
      this shift in relaxin production is poorly understood. The objective of this
      study was to observe the effect of luteinization on relaxin gene expression and
      secretion by porcine granulosa (GC) and TC using an in vitro model. TC and GC
      from medium-sized porcine follicles (4-6 mm) were treated for up to 8 days with
      LH (250 ng/ml) and/or insulin-like growth factor-I (IGF-I; 10 ng/ml). Media were
      assayed for relaxin and progesterone by RIA, changes in cell morphology were
      recorded, and total RNA was subjected to reverse transciption-polymerase chain
      reaction to monitor relaxin gene expression. In vitro luteinization, induced with
      LH + IGF-I treatment, was confirmed in both GC and TC by a change in morphology
      and a sustained, significant rise in progesterone secretion. In luteinizing GC,
      relaxin secretion was first detected after 5 treatment days, and steadily rose
      until it became significantly higher (p < 0.001) by treatment Days 7-8. In
      contrast, relaxin release from luteinizing TC was significant after only 2 days
      of treatment (p < 0.05) and increased consistently over the 8-day culture period
      (p < 0.001). In GC, relaxin mRNA was not detected until treatment Day 4 and
      became significantly higher (p < 0.001) by Day 8, the final treatment day.
      Relaxin transcript in luteinizing TC was low on treatment Days 2-4 and
      significantly higher (p < 0.01) by treatment Days 6 and 8. In summary, the
      present study demonstrates that hormones important in the control of
      luteinization are essential for regulating relaxin gene expression and secretion
      by GC and TC in the porcine follicle.

PMID- 9916021
TI  - Differential expression of immunobiological mediators by immortalized human
      cervical and vaginal epithelial cells.
AB  - We have recently generated human papillomavirus (HPV) 16/E6E7 immortalized
      epithelial cell lines from the human vagina, ectocervix, and endocervix to use in
      studies on the role of these cells in reproduction and immune defense. The cell
      lines maintain the differentiation characteristics of their tissues of origin:
      the endocervical cell line expresses characteristics of simple columnar
      epithelium, whereas the ectocervical and vaginal cell lines express
      characteristics of stratified squamous nonkeratinizing epithelia. As a first step
      in elucidating the role of these cells in immune defense, we have studied the
      expression of immunological mediators in nonstimulated and stimulated cultures.
      Without stimulation, all three lines consistently produced the cytokines
      macrophage colony-stimulating factor (M-CSF) and transforming growth factor
      beta1, the chemokine interleukin (IL)-8, prostaglandin E2, the secretory
      leukoproteinase inhibitor, and the polymeric immunoglobulin receptor. The
      endocervical cell line, but not the others, also produced the lymphopoietic
      cytokines IL-6, IL-7, and consistently detectable levels of the chemokine known
      as "regulated-upon-activation, normal T cell expressed and secreted" (RANTES).
      Stimulation with the exogenous cytokines interferon gamma and tumor necrosis
      factor alpha induced or significantly up-regulated expression of several of the
      cytokines and chemokines (i.e., IL-6, IL-8, RANTES, and M-CSF), as well as major
      histocompatibility complex (MHC) class II antigens, and membrane expression and
      shedding of the intercellular adhesion molecule-1 in all three cell lines. These
      data provide further evidence that epithelial cells in the lower human female
      genital tract participate in immunological functions, that their activity is up
      regulated by proinflammatory/immune cytokines, and that epithelial cell
      immunological functions vary at different anatomical sites in the genital tract.

PMID- 9916023
TI  - Sequential expression of zona pellucida protein genes during the oogenesis of
      domestic cats.
AB  - The aim of the present study was to determine the earliest developmental stage of
      zona pellucida (ZP) protein gene expression during oogenesis in domestic cats
      (Felis catus) by means of immunohistochemical and molecular biological methods.
      Semi-thin sections (1 microm) from domestic cat ovaries were treated with anti
      cat ZP serum raised in guinea pig, and then incubated with silver-labeled anti
      guinea pig IgG. To distinguish between the three ZP proteins, total RNA was
      extracted from freshly isolated cat primordial, primary, and secondary follicles
      as well as from cumulus-oocyte complexes (COCs) and subjected to reverse
      transcription (RT). The generated cDNAs were used for polymerase chain reaction
      (PCR) with specific feline ZPA, ZPB, and ZPC gene primers. All amplified products
      were sequenced to confirm their identity. Neither ZP mRNAs nor ZP proteins were
      detectable in primordial and early primary follicles. The immunohistological
      approach indicated the expression of ZP proteins in some of the primary follicles
      as well as in secondary follicles and COCs. Follow-up by RT-PCR revealed that
      only one ZP (ZPB) was expressed in growing primary follicles (70-80 microm),
      whereas all three ZP mRNAs were detectable in secondary follicles and COCs. We
      therefore assume a sequential synthesis of zona proteins in the cat ovary.

PMID- 9916022
TI  - Xenogeneic spermatogenesis following transplantation of hamster germ cells to
      mouse testes.
AB  - It was recently demonstrated that rat spermatogenesis can occur in the
      seminiferous tubules of an immunodeficient recipient mouse after transplantation
      of testis cells from a donor rat. In the present study, hamster donor testis
      cells were transplanted to mice to determine whether xenogeneic spermatogenesis
      would result. The hamster diverged at least 16 million years ago from the mouse
      and produces spermatozoa that are larger than, and have a shape distinctly
      different from, those of the mouse. In four separate experiments with a total of
      13 recipient mice, hamster spermatogenesis was identified in the testes of each
      mouse. Approximately 6% of the tubules examined demonstrated xenogeneic
      spermatogenesis. In addition, cryopreserved hamster testis cells generated
      spermatogenesis in recipients. However, abnormalities were noted in hamster
      spermatids and acrosomes in seminiferous tubules of recipient mice. Hamster
      spermatozoa were also found in the epididymis of recipient animals, but these
      spermatozoa generally lacked acrosomes, and heads and tails were separated. Thus,
      defects in spermiogenesis occur in hamster spermatogenesis in the mouse, which
      may reflect a limited ability of endogenous mouse Sertoli cells to support fully
      the larger and evolutionarily distant hamster germ cell. The generation of
      spermatogenesis from frozen hamster cells now adds this species to the mouse and
      rat, in which spermatogonial stem cells also can be cryopreserved. This finding
      has immediate application to valuable animals of many species, because the cells
      could be stored until suitable recipients are identified or culture techniques
      devised to expand the stem cell population.

PMID- 9916024
TI  - The inhibitory effect of intracerebroventricularly injected interleukin 1beta on
      testosterone secretion in the rat: role of steroidogenic acute regulatory
      protein.
AB  - Exposure to disease or injury often results in impaired reproductive activity
      accompanied by decreased testosterone levels. After immune activation, the
      cytokine interleukin 1-beta (IL-1beta) circulates in high concentrations, and its
      exogenous administration evokes many of the sequelae of immune activation.
      Previously, we have shown that the administration of this cytokine into the
      cerebral ventricles blunts hCG-stimulated testosterone secretion. This effect,
      though time-dependent, occurs before significant elevation of interleukin 6 in
      the peripheral bloodstream, does not depend on adrenal activation, and/or changes
      in LH concentrations, leading us to hypothesize a direct connection between the
      brain and testis. To explore this mechanism further, we isolated testicular
      tissue from rats treated intracerebroventricularly (icv) with vehicle or IL-1beta
      30 or 90 min before they were killed. We found that in vivo cytokine treatment
      blunted ex vivo testosterone secretion in response to hCG, showing that the
      mechanism is independent of circulating cytokines. Though hCG binding was
      moderately reduced by icv IL-1beta in these preparations, the extent of this
      inhibition did not explain our observations. As the first acutely and hormonally
      regulated step in the biosynthesis of testosterone is the transfer of cholesterol
      into the inner mitochondrial membrane, which is mediated by steroidogenic acute
      regulatory (StAR) protein, we hypothesized that the rapid effects of icv IL-1beta
      on testicular responsiveness to hCG might be due to reduced levels of StAR. We
      report here that StAR protein was indeed reduced in Leydig cells isolated from
      rats treated in vivo with IL-1beta. Furthermore, treatment with a water-permeable
      form of cholesterol that bypasses the requirement for StAR partially restored hCG
      stimulated testosterone secretion from testes isolated from rats treated icv with
      IL-1beta. Taken together, our data indicate that StAR plays a role in the
      suppression of testicular function evoked by central administration of IL-1beta.

PMID- 9916025
TI  - Cryopreservation of bovine pre-morula-stage in vitro matured/in vitro fertilized
      embryos after delipidation and before use in nucleus transfer.
AB  - We have determined that the tolerance of in vitro matured/in vitro fertilized
      (IVM/IVF) bovine embryos to cryopreservation at the pre-morula stage can be
      improved by removal of cytoplasmic lipid droplets by centrifugation. Nucleus
      transfer was also performed using cryopreserved, delipated (lipid droplets
      removed) 8- to 16-cell-stage blastomeres of IVM/IVF embryos as donor nuclei. In
      vitro developmental ability of the delipated embryos to the blastocyst stage (20
      of 126) was found to be equal to that of undelipated embryos (35 of 176); and of
      53 delipated embryos cryopreserved at the 8- to 16-cell stage, 12 developed into
      blastocysts in vitro after thawing. On the other hand, only 2 of 43 undelipated
      embryos and 5 of 59 sham-operated embryos survived (p < 0.05). When blastomeres
      isolated from cryopreserved, delipated 8- to 16-cell-stage embryos were used for
      nucleus transfer, 57 of 80 successfully fused with enucleated oocytes, which was
      significantly lower than the fusion rate obtained with blastomeres of unfrozen,
      undelipated embryos (93 of 104, p < 0.01). However, the developmental rate to the
      blastocyst stage for nucleus transfer embryos reconstituted with frozen,
      delipated blastomeres (9 of 57) was not different from that of the nucleus
      transfer embryos with unfrozen, undelipated embryos (23 of 93). These results
      confirm that removal of cytoplasmic lipid droplets from bovine IVM/IVF zygotes
      allows for successful cryopreservation at the 8- to 16-cell stage and that
      blastomeres from these embryos can be used as donors of karyoplasts for nucleus
      transfer.

PMID- 9916026
TI  - Preferential interactions of fluorescent probe Prodan with cholesterol.
AB  - The fluorescent probe Prodan has been widely used as a probe of model and
      biological membranes. Its fluorescent maxima in phospholipid bilayers vary as a
      function of phase state, with maxima at 485 for the liquid crystal Lalpha, 435 nm
      for the gel L'beta, and 507 nm for the interdigitated gel LbetaI phase, with
      excitation at 359 nm. These spectral changes have been used for the detection of
      phase changes among these phases. In the present study, the fluorescent
      properties and partition coefficients of Prodan in model membranes of
      phosphatidylcholines and phosphatidylethanols have been studied as a function of
      lipid phase state and cholesterol content. It is shown that the Prodan spectrum
      in the presence of cholesterol no longer reflects the known phase state of the
      lipid; in each phase state, the presence of cholesterol leads to a spectrum with
      the maximum at 435 nm, characteristic of the noninterdigitated gel phase. The
      partition coefficient of Prodan into these lipids also varies with the phase
      state, giving values of 0.35 x 10(4) in the interdigitated gel, 1.8 x 10(4) in
      the noninterdigitated gel, and 7. 6 x 10(4) in the liquid crystal phase. In the
      presence of cholesterol these partition coefficients are increased to 13 x 10(4)
      for the liquid crystal and the gel phase, and 5.1 x 10(4) in the presence of 100
      mg/ml ethanol. These results suggest that Prodan has preferential interactions
      with cholesterol, and is thus not a randomly distributed fluorescent reporter
      probe in membranes containing cholesterol. These results suggest that Prodan
      should be used only with great caution in complex lipid mixtures, particularly
      biological membranes.

PMID- 9916027
TI  - Image correlation spectroscopy. II. Optimization for ultrasensitive detection of
      preexisting platelet-derived growth factor-beta receptor oligomers on intact
      cells.
AB  - Previously we introduced image correlation spectroscopy (ICS) as an imaging
      analog of fluorescence correlation spectroscopy (FCS). Implementation of ICS with
      image collection via a standard fluorescence confocal microscope and computer
      based autocorrelation analysis was shown to facilitate measurements of absolute
      number densities and determination of changes in aggregation state for
      fluorescently labeled macromolecules. In the present work we illustrate how to
      use ICS to quantify the aggregation state of immunolabeled plasma membrane
      receptors in an intact cellular milieu, taking into account background
      fluorescence. We introduce methods that enable us to completely remove white
      noise contributions from autocorrelation measurements for individual images and
      illustrate how to perform background corrections for autofluorescence and
      nonspecific fluorescence on cell population means obtained via ICS. The
      utilization of photon counting confocal imaging with ICS analysis in combination
      with the background correction techniques outlined enabled us to achieve very low
      detection limits with standard immunolabeling methods on normal, nontransformed
      human fibroblasts (AG1523) expressing relatively low numbers of platelet-derived
      growth factor-beta (PDGF-beta) receptors. Specifically, we determined that the
      PDGF-beta receptors were preaggregated as tetramers on average with a mean
      surface density of 2.3 clusters micrometer(-2) after immunolabeling at 4
      degreesC. These measurements, which show preclustering of PDGF-beta receptors on
      the surface of normal human fibroblasts, contradict a fundamental assumption of
      the ligand-induced dimerization model for signal transduction and provide support
      for an alternative model that posits signal transduction from within preexisting
      receptor aggregates.

PMID- 9916028
TI  - Does thin filament compliance diminish the cross-bridge kinetics? A study in
      rabbit psoas fibers.
AB  - The effect of thin filament compliance on our ability to detect the cross-bridge
      kinetics was examined. Our experiment is based on the facts that in rabbit psoas
      the thin filament (1.12 micrometer) is longer than half the thick filament length
      (0.82 micrometer) and that the thick filament has a central bare zone (0.16
      micrometer). Consequently, when sarcomere length is increased from 2.1 to 2.4
      micrometer, the same number of cross-bridges is involved in force generation but
      extra series compliance is introduced in the I-band. Three apparent rate
      constants (2pia, 2pib, and 2pic) were characterized by sinusoidal analysis at pCa
      4.66. Our results demonstrate that 2pia and 2pib increased 13-16% when sarcomere
      length was increased from 2.0 to 2.5 micrometer, and 2pic decreased slightly
      (9%). This slight decrease can be explained by compression of the lattice
      spacing. These observations are at variance with the expectation based on
      increased series compliance, which predicts that the rate constants will
      decrease. We also determined compliance of the I-band during rigor. I-band
      compliance during rigor induction was 35% of sarcomere compliance at sarcomere
      length 2.4 micrometer, and 24% at sarcomere length 2.1 micrometer. We conclude
      that the presence of thin filament compliance does not seriously interfere with
      our ability to detect cross-bridge kinetics using sinusoidal analysis.

PMID- 9916029
TI  - Cooperativity between two heads of dictyostelium myosin II in in vitro motility
      and ATP hydrolysis.
AB  - To elucidate the significance of the two-headed structure of myosin II, we have
      engineered and characterized recombinant single-headed myosin II. A tail segment
      of a myosin II heavy chain fused with a His-tag was expressed in wild-type
      Dictyostelium cells. Single-headed myosin, which consists of a full length myosin
      heavy chain and a tagged tail, was isolated on the basis of the affinities for
      Nickel agarose and actin. Actin sliding velocity by the single-headed myosin was
      about half of the two-headed, whereas the minimum density of the heads to support
      continuous movement was twofold higher. Actin-activated MgATPase activity of the
      single-headed myosin in solution in the presence of 24 microM actin was less than
      half of the two headed. This decrease is primarily because of fourfold-elevated
      Kapp for actin and secondary to 40% lower Vmax. These results suggest that the
      two heads of a Dictyostelium myosin II molecule act cooperatively on an actin
      filament. We propose a mechanism by which two heads move actin efficiently based
      on the cooperativity.

PMID- 9916030
TI  - Rubber-like elasticity and volume changes in the isolated spasmoneme of giant
      Zoothamnium sp. under Ca2+-induced contraction.
AB  - Using glycerinated spasmoneme of giant Zoothamnium sp., the physical properties
      of spasmoneme before and after Ca2+-induced contraction (pCa 4.5) were
      investigated. The volume change of spasmoneme contraction was measured under zero
      tension. The length and diameter decreased by about 50% of their initial value as
      a result of contraction, which means that contraction is nearly isotropic. Thus
      the volume of spasmoneme decreased drastically by 86% of its original value. The
      swollen ratio of extended and contracted spasmoneme were 0.07 and 0.37,
      respectively. Tension-extension relationships of extended and contracted
      spasmonemes were measured. By applying the theory of rubber elasticity, the
      number of segments of a chain in originally extended spasmoneme was only 3.3,
      i.e., the chain was almost a straight one. On the other hand, the number of
      segments of a chain in contracted spasmoneme was more than 100, i.e., the chain
      was essentially a random one. Furthermore, the total number of chains in single
      spasmoneme was the same in extended and contracted spasmoneme. This means that
      the interchain cross-links of chains were not influenced by addition or removal
      of Ca2+. Moreover, the molecular weight of a chain is estimated to be at most
      about 50 kd. By considering all these results, it is concluded that the
      contractile mechanism of spasmoneme originates in the intramolecular folding and
      unfolding induced by Ca2+ binding and detaching.

PMID- 9916031
TI  - Effects of SH1 and SH2 modifications on myosin: similarities and differences.
AB  - The properties of myosin modified at the SH2 group (Cys-697) were studied and
      compared with the previously reported properties of myosin modified at the SH1
      group (Cys-707). 4-[N-[(iodoacetoxy)ethyl]-N methylamino]-7-nitrobenz-2-oxa-1, 3
      diazole (IANBD) was used for selective modification of the SH2 group on myosin.
      SH2-labeled heavy meromyosin (SH2-HMM), similar to SH1-labeled HMM (SH1-HMM), did
      not propel actin filaments in the in vitro motility assays. SH1- and SH2-HMM
      produced similar amounts of load in the mixtures with unmodified HMM; the sliding
      speed of actin filaments gradually decreased with an increase in the fraction of
      either one of the modified HMMs in the mixture. In analogy to SH1-labeled myosin
      subfragment 1 (SH1-S1), SH2-labeled S1 (SH2-S1) activated regulated actin in the
      in vitro motility assays. SH2 modification inhibited Mg-ATPase of S1 and its
      activation by actin. The weak binding of S1 to actin was unaffected whereas the
      strong binding was weakened by SH2 modification. Overall, our results demonstrate
      similar behavior of SH1- and SH2-modified myosin heads in the in vitro motility
      assays despite some differences in their enzymatic properties. The effects of
      these modifications are ascribed to the location of the SH1-SH2 helix relative to
      other functional centers of S1.

PMID- 9916032
TI  - The importance of coulombic end effects: experimental characterization of the
      effects of oligonucleotide flanking charges on the strength and salt dependence
      of oligocation (L8+) binding to single-stranded DNA oligomers.
AB  - Binding constants Kobs, expressed per site and evaluated in the limit of zero
      binding density, are quantified as functions of salt (sodium acetate)
      concentration for the interactions of the oligopeptide ligand KWK6NH2 (designated
      L8+, with ZL = 8 charges) with three single-stranded DNA oligomers (ss dT-mers,
      with |ZD| = 15, 39, and 69 charges). These results provide the first systematic
      experimental information about the effect of changing |ZD| on the strength and
      salt dependence of oligocation-oligonucleotide binding interactions. In a
      comparative study of L8+ binding to poly dT and to a short dT oligomer (|ZD| =
      10),. Proc. Natl. Acad. Sci. USA. 93:2511-2516) demonstrated the profound
      thermodynamic effects of phosphate charges that flank isolated nonspecific L8+
      binding sites on DNA. Here we find that both Kobs and the magnitude of its power
      dependence on salt activity (|SaKobs|) increase monotonically with increasing
      |ZD|. The dependences of Kobs and SaKobs on |ZD| are interpreted by introducing a
      simple two-state thermodynamic model for Coulombic end effects, which accounts
      for our finding that when L8+ binds to sufficiently long dT-mers, both DeltaGobso
      = -RT ln Kobs and SaKobs approach the values characteristic of binding to poly-dT
      as linear functions of the reciprocal of the number of potential oligocation
      binding sites on the DNA lattice. Analysis of our L8+-dT-mer binding data in
      terms of this model indicates that the axial range of the Coulombic end effect
      for ss DNA extends over approximately 10 phosphate charges. We conclude that
      Coulombic interactions cause an oligocation (with ZL < |ZD|) to bind
      preferentially to interior rather than terminal binding sites on oligoanionic or
      polyanionic DNA, and we quantify the strong increase of this preference with
      decreasing salt concentration. Coulombic end effects must be considered when
      oligonucleotides are used as models for polyanionic DNA in thermodynamic studies
      of the binding of charged ligands, including proteins.

PMID- 9916033
TI  - Conformational change of helix G in the bacteriorhodopsin photocycle:
      investigation with heavy atom labeling and x-ray diffraction.
AB  - According to the current structural model of bacteriorhodopsin, Ile222 is located
      at the cytoplasmic end of helix G. We labeled the single cysteine of the site
      directed mutant Ile222 --> Cys with p-chloromercuribenzoic acid and determined
      the position of the labeled mercury by x-ray diffraction in the unphotolyzed
      state, and in the MN photointermediate accumulated in the presence of guanidine
      hydrochloride at pH 9.5. According to the difference Fourier maps between the MN
      intermediate and the unphotolyzed state, the structural change in the MN
      intermediate was not affected by mercury labeling. The difference Fourier map
      between the labeled and the unlabeled I222C gave the position of the mercury
      label. This information was obtained for both the unphotolyzed state and the MN
      intermediate. We found that the position of the mercury at residue 222 is shifted
      by 2.1 +/- 0.8 A in the MN intermediate. This agrees with earlier results that
      suggested a structural change in the G helix. The movement of the mercury label
      is so large that it must originate from a cooperative conformational change in
      the helix G at its cytoplasmic end, rather than from displacement of residue 222.
      Because Ile222 is located at the same level on the z coordinate as Asp96, the
      structural change in the G helix could have the functional role of perturbing the
      environment and therefore the pKa of this functionally important aspartate.

PMID- 9916034
TI  - Oriented, active Escherichia coli RNA polymerase: an atomic force microscope
      study.
AB  - Combining a system for binding proteins to surfaces (Sigal, G. B., C. Bamdad, A.
      Barberis, J. Strominger, and G. M. Whitesides. 1996. Anal. Chem. 68:490-497) with
      a method for making ultraflat gold surfaces (Hegner, M., P. Wagner, and G.
      Semenza. 1993. Surface Sci. 291:39-46 1993) has enabled single, oriented, active
      Escherichia coli RNA polymerase (RNAP) molecules to be imaged under aqueous
      buffer using tapping-mode atomic force microscopy (AFM). Recombinant RNAP
      molecules containing histidine tags (hisRNAP) on the C-terminus were specifically
      immobilized on ultraflat gold via a mixed monolayer of two different omega
      functionalized alkanethiols. One alkanethiol was terminated in an ethylene-glycol
      (EG) group, which resists protein adsorption, and the other was terminated in an
      N-nitrilotriacetic acid (NTA) group, which binds the histidine tag through two
      coordination sites with a nickel ion. AFM images showed that these two
      alkanethiols phase-segregate. Specific binding of the hisRNAP molecules was
      followed in situ by injecting proteins directly into the AFM fluid cell. The
      activity of the hisRNAP bound to the NTA groups was confirmed with a 42-base
      circular single-stranded DNA template (rolling circle), which the RNAP uses to
      produce huge RNA transcripts. These transcripts were imaged in air after the
      samples were rinsed and dried, since RNA also has low affinity for the EG-thiol
      and cannot be imaged under the buffers we used.

PMID- 9916035
TI  - The temperature dependence of internal molecular motions in hydrated and dry
      alpha-amylase: the role of hydration water in the dynamical transition of
      proteins.
AB  - Internal molecular motions of proteins are strongly affected by environmental
      conditions, like temperature and hydration. As known from numerous studies, the
      dynamical behavior of hydrated proteins on the picosecond time scale is
      characterized by vibrational motions in the low-temperature regime and by an
      onset of stochastic large-amplitude fluctuations at a transition temperature of
      180-230 K. The present study reports on the temperature dependence of internal
      molecular motions as measured with incoherent neutron scattering from the
      globular water-soluble protein alpha-amylase and from a protein-lipid complex of
      rhodopsin in disk membranes. Samples of alpha-amylase have been measured in a
      hydrated and dehydrated state. In contrast to the hydrated sample, which exhibits
      a pronounced dynamical transition near 200 K, the dehydrated alpha-amylase does
      not show an appreciable proportion of stochastic large-amplitude fluctuations and
      no dynamical transition in the measured temperature range of 140-300 K. The
      obtained results, which are compared to the dynamical behavior of protein-lipid
      complexes, are discussed with respect to the influence of hydration on the
      dynamical transition and in the framework of the glass transition.

PMID- 9916036
TI  - Harmonic behavior of trehalose-coated carbon-monoxy-myoglobin at high
      temperature.
AB  - Embedding biostructures in saccharide glasses protects them against extreme
      dehydration and/or exposure to very high temperature. Among the saccharides,
      trehalose appears to be the most effective bioprotectant. In this paper we report
      on the low-frequency dynamics of carbon monoxy myoglobin in an extremely dry
      trehalose glass measured by neutron spectroscopy. Under these conditions, the
      mean square displacements and the density of state function are those of a
      harmonic solid, up to room temperature, in contrast to D2O-hydrated myoglobin, in
      which a dynamical transition to a nonharmonic regime has been observed at
      approximately 180 K (Doster et al., 1989. Nature. 337:754-756). The protective
      effect of trehalose is correlated, therefore, with a trapping of the protein in a
      harmonic potential, even at relatively high temperature.

PMID- 9916037
TI  - Ultrastructural studies on scrapie prion protein crystals obtained from reverse
      micellar solutions.
AB  - The structural transition from the cellular prion protein (PrPC) that is rich in
      alpha-helices to the pathological form (PrPSc) that has a high beta-sheet content
      seems to be the fundamental event underlying the prion diseases. Determination of
      the structure of PrPSc and the N-terminally truncated PrP 27-30 has been
      complicated by their insolubility. Here we report the solubilization of PrP 27-30
      through a system of reverse micelles that yields monomeric and dimeric PrP.
      Although solubilization of PrP 27-30 was not accompanied by any recognizable
      change in secondary structure as measured by FTIR spectroscopy, it did result in
      a loss of prion infectivity. The formation of small two- and three-dimensional
      crystals upon exposure to uranyl salts argues that soluble PrP 27-30 possesses
      considerable tertiary structure. The crystals of PrP 27-30 grown from reverse
      micellar solutions suggest a novel crystallization mechanism that might be
      applicable for other membrane proteins. A variety of different crystal lattices
      diffracted up to 1.85 nm by electron microscopy. Despite the lack of measurable
      biological activity, the structure of PrP 27-30 in these crystals may provide
      insight into the structural transition that occurs during PrPSc formation.

PMID- 9916038
TI  - Diffusing wave spectroscopy microrheology of actin filament networks.
AB  - Filamentous actin (F-actin), one of the constituents of the cytoskeleton, is
      believed to be the most important participant in the motion and mechanical
      integrity of eukaryotic cells. Traditionally, the viscoelastic moduli of F-actin
      networks have been measured by imposing a small mechanical strain and quantifying
      the resulting stress. The magnitude of the viscoelastic moduli, their
      concentration dependence and strain dependence, as well as the viscoelastic
      nature (solid-like or liquid-like) of networks of uncross-linked F-actin, have
      been the subjects of debate. Although this paper helps to resolve the debate and
      establishes the extent of the linear regime of F-actin networks' rheology, we
      report novel measurements of the high-frequency behavior of networks of F-actin,
      using a noninvasive light-scattering based technique, diffusing wave spectroscopy
      (DWS). Because no external strain is applied, our optical assay generates
      measurements of the mechanical properties of F-actin networks that avoid many
      ambiguities inherent in mechanical measurements. We observe that the elastic
      modulus has a small magnitude, no strain dependence, and a weak concentration
      dependence. Therefore, F-actin alone is not sufficient to generate the elastic
      modulus necessary to sustain the structural rigidity of most cells or support new
      cellular protrusions. Unlike previous studies, our measurements show that the
      mechanical properties of F-actin are highly dependent on the frequency content of
      the deformation. We show that the loss modulus unexpectedly dominates the elastic
      modulus at high frequencies, which are key for fast transitions. Finally, the
      measured mean square displacement of the optical probes, which is also generated
      by DWS measurements, offers new insight into the local bending fluctuations of
      the individual actin filaments and shows how they generate enhanced dissipation
      at short time scales.

PMID- 9916040
TI  - High-resolution, submicron particle size distribution analysis using
      gravitational-sweep sedimentation.
AB  - Sedimentation velocity is a powerful tool for the analysis of complex solutions
      of macromolecules. However, sample turbidity imposes an upper limit to the size
      of molecular complexes currently amenable to such analysis. Furthermore, the
      breadth of the particle size distribution, combined with possible variations in
      the density of different particles, makes it difficult to analyze extremely
      complex mixtures. These same problems are faced in the polymer industry, where
      dispersions of latices, pigments, lacquers, and emulsions must be characterized.
      There is a rich history of methods developed for the polymer industry finding use
      in the biochemical sciences. Two such methods are presented. These use analytical
      ultracentrifugation to determine the density and size distributions for submicron
      sized particles. Both methods rely on Stokes' equations to estimate particle size
      and density, whereas turbidity, corrected using Mie's theory, provides the
      concentration measurement. The first method uses the sedimentation time in
      dispersion media of different densities to evaluate the particle density and size
      distribution. This method works provided the sample is chemically homogeneous.
      The second method splices together data gathered at different sample
      concentrations, thus permitting the high-resolution determination of the size
      distribution of particle diameters ranging from 10 to 3000 nm. By increasing the
      rotor speed exponentially from 0 to 40,000 rpm over a 1-h period, size
      distributions may be measured for extremely broadly distributed dispersions.
      Presented here is a short history of particle size distribution analysis using
      the ultracentrifuge, along with a description of the newest experimental methods.
      Several applications of the methods are provided that demonstrate the breadth of
      its utility, including extensions to samples containing nonspherical and
      chromophoric particles.

PMID- 9916039
TI  - Force measurements on myelin basic protein adsorbed to mica and lipid bilayer
      surfaces done with the atomic force microscope.
AB  - The mechanical and adhesion properties of myelin basic protein (MBP) are
      important for its function, namely the compaction of the myelin sheath. To get
      more information about these properties we used atomic force microscopy to study
      tip-sample interaction of mica and mixed dioleoylphosphatidylserine (DOPS)
      (20%)/egg phosphatidylcholine (EPC) (80%) lipid bilayer surfaces in the absence
      and presence of bovine MBP. On mica or DOPS/EPC bilayers a short-range repulsive
      force (decay length 1.0-1.3 nm) was observed during the approach. The presence of
      MBP always led to an attractive force between tip and sample. When retracting the
      tip again, force curves on mica and on lipid layers were different. While
      attached to the mica surface, the MBP molecules exhibited elastic stretching
      behavior that agreed with the worm-like chain model, yielding a persistence
      length of 0.5 +/- 0.25 nm and an average contour length of 53 +/- 19 nm. MBP
      attached to a lipid bilayer did not show elastic stretching behavior. This shows
      that the protein adopts a different conformation when in contact with lipids. The
      lipid bilayer is strongly modified by MBP attachment, indicating formation of MBP
      lipid complexes and possibly disruption of the original bilayer structure.

PMID- 9916041
TI  - Picosecond multiphoton scanning near-field optical microscopy.
AB  - We have implemented simultaneous picosecond pulsed two- and three-photon
      excitation of near-UV and visible absorbing fluorophores in a scanning near-field
      optical microscope (SNOM). The 1064-nm emission from a pulsed Nd:YVO4 laser was
      used to excite the visible mitochondrial specific dye MitoTracker Orange CM
      H2TMRos or a Cy3-labeled antibody by two-photon excitation, and the UV absorbing
      DNA dyes DAPI and the bisbenzimidazole BBI-342 by three-photon excitation, in a
      shared aperture SNOM using uncoated fiber tips. Both organelles in human breast
      adenocarcinoma cells (MCF 7) and specific protein bands on polytene chromosomes
      of Drosophila melanogaster doubly labeled with a UV and visible dye were readily
      imaged without photodamage to the specimens. The fluorescence intensities showed
      the expected nonlinear dependence on the excitation power over the range of 5-40
      mW. An analysis of the dependence of fluorescence intensity on the tip-sample
      displacement normal to the sample surface revealed a higher-order function for
      the two-photon excitation compared to the one-photon mode. In addition, the
      sample photobleaching patterns corresponding to one- and two-photon modes
      revealed a greater lateral confinement of the excitation in the two-photon case.
      Thus, as in optical microscopy, two-photon excitation in SNOM is confined to a
      smaller volume.

PMID- 9916042
TI  - Electrostatically balanced subnanometer imaging of biological specimens by atomic
      force microscope.
AB  - To achieve high-resolution topographs of native biological macromolecules in
      aqueous solution with the atomic force microscope (AFM) interactions between AFM
      tip and sample need to be considered. Short-range forces produce the submolecular
      information of high-resolution topographs. In contrast, no significant high
      resolution information is provided by the long-range electrostatic double-layer
      force. However, this force can be adjusted by pH and electrolytes to distribute
      the force applied to the AFM tip over a large sample area. As demonstrated on
      fragile biological samples, adjustment of the electrolyte solution results in a
      local reduction of both vertical and lateral forces between the AFM tip and
      proteinous substructures. Under such electrostatically balanced conditions, the
      deformation of the native protein is minimized and the sample surface can be
      reproducibly contoured at a lateral resolution of 0.6 nm.

PMID- 9916043
TI  - Probabilistic modeling of shear-induced formation and breakage of doublets cross
      linked by receptor-ligand bonds.
AB  - A model was constructed to describe previously published experiments of shear
      induced formation and breakage of doublets of red cells and of latexes cross
      linked by receptor-ligand bonds (. Biophys. J. 65:1318-1334; Tees and Goldsmith.
      1996. Biophys. J. 71:1102-1114;. Biophys. J. 71:1115-1122). The model, based on
      McQuarrie's master equations (1963. J. Phys. Chem. 38:433-436), provides unifying
      treatments for three distinctive time periods in the experiments of particles in
      a Couette flow in which a doublet undergoes 1) formation upon two-body collision
      between singlets; 2) evolution of bonds at low shear rate; and 3) break-up at
      high shear rate. Neglecting the applied force at low shear rate, the probability
      of forming a doublet per collision as well as the evolution of probability
      distribution of bonds in a preformed doublet were solved analytically and found
      to be in quite good agreement with measurements. At high shear rate with
      significant force acting to accelerate bond dissociation, the predictions for
      break-up of doublets were obtained numerically and compared well with data in
      both individual and population studies. These comparisons enabled bond kinetic
      parameters for three types of particles cross-linked by two receptor-ligand
      systems to be calculated, which agreed well with those computed from Monte Carlo
      simulations. This work can be extended to analyze kinetics of receptor-ligand
      binding in cell aggregates, such as those of neutrophils and platelets in the
      circulation.

PMID- 9916044
TI  - Microamperometric measurements of photosynthetic activity in a single algal
      protoplast.
AB  - The effects of p-benzoquinone (BQ) on photosynthetic and respiratory electron
      transport in a single algal protoplast (radius, 100 microm) was investigated
      quantitatively by amperometric measurements using microelectrodes. Under light
      irradiation (25 kLx) in the presence of 1.00 mM BQ, a single protoplast consumed
      BQ by (2.9 +/- 0.2) x 10(-13) mol/s and generated p-hydroquinone (QH2) by (2.7 +/
      0.3) x 10(-13) mol/s, suggesting that BQ was quantitatively reduced to QH2 via
      the intracellular photosynthetic electron-transport chain. The generation of QH2
      increased with light intensity and with concentration of BQ added to the outside
      solution but became saturated when the light intensity was above 15 kLx or the BQ
      concentration was higher than 0.75 mM. The addition of 3-(3, 4-dichlorophenyl)
      1,1-dimethylurea, a photosynthetic electron-transport inhibitor, decreased the
      generation of QH2 upon light irradiation, suggesting that BQ accepts electrons
      from a site in the photosynthetic electron-transport chain after the photosystem
      II site. The presence of 1.00 mM BQ increased the generation of photosynthetic
      oxygen by approximately (2.6 +/- 1.0) x 10(-13) mol/s, which was approximately
      1.5-2 times larger than that expected from the consumption of BQ. The electrons
      produced by the additional generation of oxygen is used to reduce intracellular
      species as well as to reduce BQ.

PMID- 9916045
TI  - Membrane dynamics of the water transport protein aquaporin-1 in intact human red
      cells.
AB  - Aquaporin-1 (AQP1) is the prototype integral membrane protein water channel.
      Although the three-dimensional structure and water transport function of the
      molecule have been described, the physical interactions between AQP1 and other
      membrane components have not been characterized. Using fluorescein isothiocyanate
      anti-Co3 (FITC-anti-Co3), a reagent specific for an extracellular epitope on
      AQP1, the fluorescence photobleaching recovery (FPR) and fluorescence imaged
      microdeformation (FIMD) techniques were performed on intact human red cells. By
      FPR, the fractional mobility of fluorescently labeled AQP1 (F-alphaAQP1) in the
      undeformed red cell membrane is 66 +/- 10% and the average lateral diffusion
      coefficient is (3.1 +/- 0.5) x 10(-11) cm2/s. F-alphaAQP1 fractional mobility is
      not significantly affected by antibody-induced immobilization of the major
      integral proteins band 3 or glycophorin A, indicating that AQP1 does not exist as
      a complex with these proteins. FIMD uses pipette aspiration of individual red
      cells to create a constant but reversible skeletal density gradient. F-alphaAQP1
      distribution, like that of lipid-anchored proteins, is not at equilibrium after
      microdeformation. Over time, approximately 50% of the aspirated F-alphaAQP1
      molecules migrate toward the membrane portion that had been maximally dilated,
      the aspirated cap. Based on the kinetics of migration, the F-alphaAQP1 lateral
      diffusion coefficient in the membrane projection is estimated to be 6 x 10(-10)
      cm2/s. These results suggest that AQP1 lateral mobility is regulated in the
      unperturbed membrane by passive steric hindrance imposed by the spectrin-based
      membrane skeleton and/or by skeleton-linked membrane components, and that release
      of these constraints by dilatation of the skeleton allows AQP1 to diffuse much
      more rapidly in the plane of the membrane.

PMID- 9916046
TI  - A new determination of the shear modulus of the human erythrocyte membrane using
      optical tweezers.
AB  - Optical tweezers are used to apply calibrated forces to human erythrocytes, via
      small silica beads bound to their membrane. The shear modulus mu of the membrane
      is inferred from measurements of the cell deformation in the small strain linear
      regime. We find the same result mu = 2.5 +/- 0.4 microN/m for both discotic and
      nearly spherical swollen cells. This value is smaller than the one deduced from
      micropipettes experiments. However the two methods do not operate in the same
      deformation regime and are not expected to lead to the same result.

PMID- 9916047
TI  - The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria
      and bypasses bactericidal responses in human macrophages.
AB  - The mannose receptor (MR) is involved in the phagocytosis of pathogenic
      microorganisms. Here we investigated its role in the bactericidal functions of
      human monocyte-derived macrophages (MDMs), using (i) trimannoside-bovine serum
      albumin (BSA)-coated latex beads and zymosan as particulate ligands of the MR,
      and (ii) mannan and mannose-BSA as soluble ligands. We show that phagocytosis of
      mannosylated latex beads did not elicit the production of O2-. Zymosan, which is
      composed of alpha-mannan and beta-glucan, was internalized by the MR and a beta
      glucan receptor, but the production of O2- was triggered only by phagocytosis
      through the beta-glucan receptor. Activation and translocation of Hck, a Src
      family tyrosine kinase located on lysosomes, has previously been used as a marker
      of fusion between lysosomes and phagosomes in human neutrophils. In MDMs, Hck was
      activated and recruited to phagosomes containing zymosan later than LAMP-1 and
      CD63. Phagosomes containing mannosylated latex beads fused with LAMP-1 and CD63
      vesicles but not with the Hck compartment, and the kinase was not activated. We
      also demonstrate that the MR was unable to distinguish between nonpathogenic and
      pathogenic mycobacteria, as they were internalized at similar rates by this
      receptor, indicating that this route of entry cannot be considered as a
      differential determinant of the intracellular fate of mycobacteria. In
      conclusion, MR-dependent phagocytosis is coupled neither to the activation of
      NADPH oxidase nor to the maturation of phagosomes until fusion with the Hck
      compartment and therefore constitutes a safe portal of entry for microorganisms.

PMID- 9916048
TI  - Interleukin 18 contributes to host resistance and gamma interferon production in
      mice infected with virulent Salmonella typhimurium.
AB  - Spleen and peritoneal macrophages obtained from innately resistant A/J mice
      released low levels of interleukin 18 (IL-18) upon infection with Salmonella
      typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN
      gamma) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18
      antibodies showed impaired resistance to infection, with increased bacterial
      loads in the liver and spleen. Administration of rIL-18 could protect A/J mice
      from challenge with a lethal dose of virulent salmonellae, with a dramatic
      reduction in bacterial numbers in the tissues. rIL-18 administration did not
      ameliorate the disease in IFN-gamma-R-/- mice. IL-18 proved to be required for
      IFN-gamma production by mouse splenocytes from conventional, scid, and rag-1(-/-)
      mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-gamma
      levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and
      probably acts via IFN-gamma.

PMID- 9916049
TI  - Natural immunity to Ascaris lumbricoides associated with immunoglobulin E
      antibody to ABA-1 allergen and inflammation indicators in children.
AB  - Children putatively immune to the large roundworm Ascaris lumbricoides were
      identified in an area of Nigeria where infection is hyperendemic. Immunity was
      associated with higher levels of serum ferritin, C-reactive protein, and
      eosinophil cationic protein, indicating ongoing acute phase or inflammatory
      processes. In contrast, children who were susceptible to the infection had little
      serological evidence of inflammation despite their high parasite burdens.
      Immunoglobulin G (IgG) antibody activity in all subclasses was present in high
      titer in most children but appeared to have no protective function. Despite
      exceptionally high total IgE levels, there was no evidence that atopic responses
      to local common allergens was associated with natural immunity to Ascaris. Among
      those individuals who produced IgG antibody to recombinant ABA-1 allergen of
      Ascaris, the naturally immune group had significantly more IgE antibody to the
      allergen than did those susceptible to the infection. IgE antibody responses in
      conjunction with innate inflammatory processes therefore appear to associate with
      natural immunity to ascariasis.

PMID- 9916050
TI  - Enteropathogenic Escherichia coli inhibits phagocytosis.
AB  - Enteropathogenic Escherichia coli (EPEC) interacts with intestinal epithelial
      cells, activating host signaling pathways leading to cytoskeletal rearrangements
      and ultimately diarrhea. In this study, we demonstrate that EPEC interacts with
      the macrophage-like cell line J774A.1 to inhibit phagocytosis by these cells.
      Antiphagocytic activity was also observed in cultured RAW macrophage-like cells
      upon EPEC infection. The EPEC antiphagocytic phenotype was dependent on the type
      III secretion pathway of EPEC and its secreted proteins, including EspA, EspB,
      and EspD. Intimin and Tir mutants displayed intermediate antiphagocytic activity,
      suggesting that intimate attachment mediated by intimin-Tir binding may also play
      a role in antiphagocytosis. Tyrosine dephosphorylation of several host proteins
      was observed following infection with secretion-competent EPEC but not with
      secretion-deficient mutants. Dephosphorylation was detectable 120 min after
      infection with EPEC, directly correlating with the onset of the antiphagocytic
      phenotype. Inhibition of protein tyrosine phosphatases by pervanadate treatment
      increased the number of intracellular wild-type EPEC organisms to levels seen
      with secretion-deficient mutants, suggesting that dephosphorylation events are
      linked to the antiphagocytic phenotype. No tyrosine phosphatase activity was
      detected with the EPEC-secreted proteins, suggesting that EPEC induces
      antiphagocytosis via a different mechanism than Yersinia species. Taken together,
      the present findings demonstrate a novel function for EPEC-secreted proteins in
      triggering macrophage protein tyrosine dephosphorylation and inhibition of
      phagocytosis.

PMID- 9916051
TI  - Deamidation of Cdc42 and Rac by Escherichia coli cytotoxic necrotizing factor 1:
      activation of c-Jun N-terminal kinase in HeLa cells.
AB  - Recently, Escherichia coli cytotoxic necrotizing factor 1 (CNF1) was shown to
      activate the low-molecular-mass GTPase RhoA by deamidation of Gln63, thereby
      inhibiting intrinsic and GTPase-activating protein (GAP)-stimulated GTPase
      activities (G. Schmidt, P. Sehr, M. Wilm, J. Selzer, M. Mann, and K. Aktories,
      Nature 387:725-729, 1997; G. Flatau, E. Lemichez, M. Gauthier, P. Chardin, S.
      Paris, C. Fiorentini, and P. Boquet, Nature 387:729-733, 1997). Here we report
      that in addition to RhoA, Cdc42 and Rac also are targets for CNF1 in vitro and in
      intact cells. Treatment of HeLa cells with CNF1 induced a transient formation of
      microspikes and formation of membrane ruffles. CNF1 caused a transient 10- to 50
      fold increase in the activity of the c-Jun N-terminal kinase. Tryptic peptides of
      Cdc42 obtained from CNF1-treated cells by immunoprecipitation exhibited an
      increase in mass of 1 Da compared to control peptides, indicating the deamidation
      of glutamine 61 by the toxin. The same increase in mass was observed with the
      respective peptides obtained from CNF1-modified recombinant Cdc42 and Rac1.
      Modification of recombinant Cdc42 and Rac1 by CNF1 inhibited intrinsic and GAP
      stimulated GTPase activities and retarded binding of 2'(3')-O-(N
      methylanthraniloyl)GDP. The data suggest that recombinant as well as cellular
      Cdc42 and Rac are substrates for CNF1.

PMID- 9916052
TI  - Genetic and physiologic characterization of urease of Actinomyces naeslundii.
AB  - Ammonia production from urea by ureolytic oral bacteria is believed to have a
      significant impact on oral health and the ecological balance of oral microbial
      populations. In this study we cloned and characterized the urease gene cluster of
      Actinomyces naeslundii, which is one of the pioneer organisms in the oral cavity
      and a significant constituent of supragingival and subgingival dental plaque in
      children and adults. An internal fragment of the ureC gene of A. naeslundii WVU45
      was initially amplified by PCR with degenerate primers derived from conserved
      amino acid sequences of the large catalytic subunit of urease in bacteria and
      plants. The PCR product was then used as a probe to identify recombinant
      bacteriophages carrying the A. naeslundii urease gene cluster and roughly 30 kbp
      of flanking DNA. Nucleotide sequence analysis demonstrated that the gene cluster
      was comprised of seven contiguously arranged open reading frames with significant
      homologies at the protein and nucleotide sequence levels to the ureABCEFGD genes
      from other organisms. By using primer extension, a putative transcription
      initiation site was mapped at 66 bases 5' to the start codon of ureA. A urease
      deficient strain was constructed by insertion of a kanamycin resistance
      determinant within the ureC gene via allelic replacement. In contrast to the wild
      type organism, the isogenic mutant was unable to grow in a semidefined medium
      supplemented with urea as the nitrogen source and was not protected by the
      addition of urea against killing in moderately acidic environments. These data
      indicated that urea can be effectively utilized as a nitrogen source by A.
      naeslundii via a urease-dependent pathway and that ureolysis can protect A.
      naeslundii against environmental acidification at physiologically relevant pH
      values. Therefore, urease could confer to A. naeslundii critical selective
      advantages over nonureolytic organisms in dental plaque, constituting an
      important determinant of plaque ecology.

PMID- 9916053
TI  - Therapy with a combination of low doses of interleukin 12 and chloroquine
      completely cures blood-stage malaria, prevents severe anemia, and induces
      immunity to reinfection.
AB  - The immunoregulatory cytokine interleukin 12 (IL-12) induces host resistance
      against experimental malaria. In this study, we tested the feasibility of using
      IL-12 in combination with chloroquine (CQ) to rescue susceptible A/J mice from
      lethal blood-stage Plasmodium chabaudi AS infection. Combined treatment with low
      doses of CQ and IL-12 resulted in a >15-fold reduction in the parasite load and
      100% survival of A/J mice with established infections. Compared to control mice,
      which succumbed to severe anemia, CQ-plus-IL-12-treated mice had significantly
      higher early- and late-stage erythroid-cell progenitors in the bone marrow and
      spleen, resulting in significantly higher hematocrits, erythrocyte counts, and
      percentages of reticulocytes. Production of parasite-specific gamma interferon
      (IFN-gamma) by splenocytes from these mice was upregulated >20-fold relative to
      controls in parallel with enhanced IFN-gamma mRNA expression. Further, enhanced
      responsiveness to IL-12 and increased downstream IFN-gamma production in CQ-plus
      IL-12-treated mice was evident from increased mRNA expression for the beta1 and
      beta2 subunits of IL-12 receptor in the splenocytes. Moreover, this combined
      therapy induced higher levels of anti-malaria antibodies than did CQ alone as
      well as sterile immunity against reinfection. Because IL-12 can be used at low
      doses and is effective even in established infections, it may be feasible to use
      this immunochemotherapeutic approach in human malaria.

PMID- 9916054
TI  - Receptor-dependent immune responses in pigs after oral immunization with F4
      fimbriae.
AB  - F4 receptor-positive (F4R+) and F4 receptor-negative (F4R-) pigs were orally
      vaccinated with purified F4 fimbriae of enterotoxigenic Escherichia coli (ETEC).
      Serum immunoglobulin G (IgG) and IgA responses were readily detected in F4R+
      animals, whereas immune responses were not detected in F4R- animals. Even after a
      subsequent oral infection with virulent F4(+) ETEC and a booster immunization
      with F4, the F4R- animals remained F4 seronegative whereas the unvaccinated F4R+
      pigs exhibited clear IgA and IgG responses. These results clearly demonstrate
      that F4Rs are a prerequisite for an immune response following oral immunization.
      Furthermore, indications that oral F4 vaccination can induce mucosal protection
      were obtained, since the experimental ETEC infection did not induce a systemic
      booster response or fecal ETEC excretion in orally vaccinated F4R+ pigs, in
      contrast to the clear immune response and ETEC excretion of unvaccinated F4R+
      animals. F4-specific IgA antibodies could be found in the feces of the vaccinated
      F4R+ pigs. They are secreted at the intestinal mucosal surface and appear to
      prevent ETEC infection. The F4R-dependent induction of a mucosal immune response
      can be used as a model to better understand mucosal immunization and mucosal
      immune responses and can contribute to the development of oral vaccines in
      veterinary as well as in human medicine.

PMID- 9916055
TI  - Serum antitoxin antibodies mediate systemic and mucosal protection from
      Clostridium difficile disease in hamsters.
AB  - Clostridium difficile is the bacterial pathogen identified as the cause of
      pseudomembranous colitis and is principally responsible for nosocomial antibiotic
      associated diarrhea and colitis. The pathologic findings associated with this
      infection are believed to be caused by two large (approximately 300-kDa)
      exotoxins, toxins A and B. Because of the mucosal nature of this infection,
      vaccination strategies aimed at providing prophylactic or therapeutic immune
      protection have included immunization by mucosal routes. Using the hamster model
      of C. difficile infection, we examined the protective efficacy of inactivated
      toxin (toxoid) vaccine formulations prepared as either culture filtrate or
      partially purified toxoid. We compared combination parenteral and mucosal
      vaccination regimens involving intranasal, intragastric, or rectal routes of
      immunization and found that rectal immunization in conjunction with intramuscular
      (i.m.) vaccination provided full protection of hamsters from death and diarrhea
      while the other mucosal routes did not. Protection was associated with high
      levels of toxin-neutralizing antibodies in serum. The requirement for adjuvants
      for protection was assessed by using sequential i.m. and rectal or i.m.
      vaccination regimens. Unexpectedly, i.m. immunization without adjuvant conferred
      the highest protection from death and diarrhea; this regimen elicited the highest
      serum anti-toxin B titers as well as toxin B neutralizing titers. Passive
      transfer of mouse antitoxin antibodies protected hamsters in a dose-dependent
      manner, demonstrating the principal role of circulating antitoxin antibodies in
      immunity from this toxin-mediated mucosal disease. These results suggest that
      prophylactic parenteral vaccination or intravenous immunotherapy could provide
      protection from C. difficile disease in humans.

PMID- 9916056
TI  - Preliminary assessment of the safety and immunogenicity of a new CTXPhi-negative,
      hemagglutinin/protease-defective El Tor strain as a cholera vaccine candidate.
AB  - Vibrio cholerae 638 (El Tor, Ogawa), a new CTXPhi-negative hemagglutinin/protease
      defective strain that is a cholera vaccine candidate, was examined for safety and
      immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled
      study, no significant adverse reactions were observed in volunteers ingesting
      strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who
      received placebo experienced loose stools. The strain strongly colonized the
      human small bowel, as evidenced by its isolation from the stools of 37 of 42
      volunteers. V. cholerae 638, at doses ranging from 4 x 10(7) to 2 x 10(9)
      vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa
      immunoglobulin A antibody secreting cell responses.

PMID- 9916057
TI  - The link between phylogeny and virulence in Escherichia coli extraintestinal
      infection.
AB  - Previous studies suggesting a link between Escherichia coli phylogenetic groups
      and extraintestinal virulence have been hampered by the difficulty in
      establishing the intrinsic virulence of a bacterial strain. Indeed, unidentified
      virulence factors do exist, and the susceptibility of the host to infection is
      highly variable. To overcome these difficulties, we have developed a mouse model
      of extraintestinal virulence to test the virulence of the strains under
      normalized conditions. We then assessed the phylogenetic relationships compared
      to the E. coli reference (ECOR) collection, the presence of several known
      virulence determinants, and the lethality to mice of 82 human adult E. coli
      strains isolated from normal feces and during the course of extraintestinal
      infections. Commensal strains belong mainly to phylogenetic groups A and B1, are
      devoid of virulence determinants, and do not kill the mice. Strains exhibiting
      the same characteristics as the commensal strains can be isolated under
      pathogenic conditions, thus indicating the role of host-dependent factors, such
      as susceptibility linked to underlying disease, in the development of infection.
      Some strains of phylogenetic groups A, B1, and D are able to kill the mice, their
      virulence being most often correlated with the presence of virulence
      determinants. Lastly, strains of the B2 phylogenetic group represent a divergent
      lineage of highly virulent strains which kill the mice at high frequency and
      possess the highest level of virulence determinants. The observed link between
      virulence and phylogeny could correspond to the necessity of virulence
      determinants in a genetic background that is adequate for the emergence of a
      virulent clone, an expression of the interdependency of pathogenicity and
      metabolic activities in pathogenic bacteria.

PMID- 9916058
TI  - Consequences of reduction of Klebsiella pneumoniae capsule expression on
      interactions of this bacterium with epithelial cells.
AB  - Most Klebsiella pneumoniae clinical isolates are fully encapsulated and adhere in
      vitro to intestinal cell lines with an aggregative pattern. In this study, the
      influence of the capsule on interactions with epithelial cells was investigated
      by creating an isogenic mutant defective in the synthesis of the capsule.
      Determination of the uronic acid content of bacterial extracts confirmed that the
      mutant did not produce capsular polysaccharides whereas, with the wild-type
      strain, the level of encapsulation was growth phase dependent and reached a
      maximum during the lag and early log phases. Assays performed with different
      epithelial cell lines, Int-407, A-549, and HEp-2, showed that the capsule
      defective mutant demonstrated greater adhesion than did the wild-type strain and
      that the aggregative pattern was maintained, indicating that the capsule was not
      related to the adhesion phenotype. In contrast, when the mucus-producing HT-29
      MTX cells were used, the encapsulated wild-type strain adhered more strongly than
      did the capsule-defective mutant. No invasion properties were observed with any
      of the capsular phenotypes or cell lines used. The K. pneumoniae adhesin CF29K
      was detected by Western blot analysis and enzyme-linked immunosorbent assay on
      the surface of transconjugants obtained after transfer of a conjugative plasmid
      harboring the CF29K-encoding genes into both the wild-type and the capsule
      defective strains. The amounts of adhesin detected were greater in the capsule
      defective background strain than in the wild-type encapsulated strain and were
      associated with an increase in the level of adhesion to Caco-2 cells. Moreover,
      RNA slot blot experiments showed that transcription of the adhesin-encoding gene
      was markedly increased in the capsule-defective mutant compared to the wild-type
      encapsulated background. These results suggest (i) that the capsule plays an
      active role during the initial steps of the pathogenesis by interacting with
      mucus-producing cells but is subsequently not required for the adhesin-related
      interaction with the epithelial cell surface and (ii) that the expression of the
      adhesin is modulated by the presence of a capsule at a transcriptional level.

PMID- 9916059
TI  - Vaccination against anthrax with attenuated recombinant strains of Bacillus
      anthracis that produce protective antigen.
AB  - The protective efficacy of several live, recombinant anthrax vaccines given in a
      single-dose regimen was assessed with Hartley guinea pigs. These live vaccines
      were created by transforming DeltaANR and DeltaSterne, two nonencapsulated,
      nontoxinogenic strains of Bacillus anthracis, with four different recombinant
      plasmids that express the anthrax protective antigen (PA) protein to various
      degrees. This enabled us to assess the effect of the chromosomal background of
      the strain, as well as the amount of PA produced, on protective efficacy. There
      were no significant strain-related effects on PA production in vitro, plasmid
      stability in vivo, survival of the immunizing strain in the host, or protective
      efficacy of the immunizing infection. The protective efficacy of the live,
      recombinant anthrax vaccine strains correlated with the anti-PA antibody titers
      they elicited in vivo and the level of PA they produced in vitro.

PMID- 9916060
TI  - Induction of protective T cells against Listeria monocytogenes in mice by
      immunization with a listeriolysin O-negative avirulent strain of bacteria and
      liposome-encapsulated listeriolysin O.
AB  - Only listeriolysin O (LLO)-producing strains of Listeria monocytogenes generate
      protective immunity in mice. Based on the findings that endogenous gamma
      interferon (IFN-gamma) production was induced only by such strains and that
      purified LLO could induce IFN-gamma from NK cells, we have postulated that LLO
      may play a pivotal role in the induction of Th1-type protective T cells, which
      are highly dependent on IFN-gamma. In this study, mice were immunized with L.
      monocytogenes ATCC 15313, an LLO-nonproducing avirulent strain, along with LLO
      encapsulated in liposome (LLO-liposome). LLO-liposome was highly potent in the
      induction of various cytokines, including IFN-gamma. Immunization of mice with
      either LLO-liposome or the viable strain ATCC 15313 alone did not induce
      protection against challenge infection. In contrast, the combination of LLO
      nonproducing bacteria plus LLO-liposome induced a significant level of protective
      immunity mediated mainly by Th1-type cells capable of producing a large amount of
      IFN-gamma in an antigen-specific manner. The protection afforded by the
      combination was not dependent on LLO-specific cytotoxic T cells. These results
      support the idea that the inability of an LLO-nonproducing avirulent strain or
      killed bacteria to induce the generation of protective T cells is due not to the
      lack of a central T-cell epitope(s) but to the lack of ability to induce the
      production of endogenous cytokine during the early stage of immunization; the
      results also suggest that an appropriate use of LLO at least in an animal model
      may be effective in the induction of antigen-specific Th1-dependent protective
      immunity to various kinds of intracellular parasitic bacteria.

PMID- 9916061
TI  - Binding and utilization of human transferrin by Prevotella nigrescens.
AB  - To survive and multiply within their hosts, pathogens must possess efficient iron
      scavenging mechanisms. In the present study, we investigate the capacity of
      Prevotella nigrescens and Prevotella intermedia to use various sources of iron
      for growth and characterize the transferrin-binding activity of P. nigrescens.
      Iron-saturated human transferrin and lactoferrin, but not ferric chloride and the
      iron-free form of transferrin, could be used as sources of iron by P. nigrescens
      and P. intermedia. Neither siderophore activity nor ferric reductase activity
      could be detected in P. nigrescens and P. intermedia. However, both species
      showed transferrin-binding activity as well as the capacity to proteolytically
      cleave transferrin. To various extents, all strains of P. nigrescens and P.
      intermedia tested demonstrated transferrin-binding activity. The activity was
      heat and protease sensitive. The capacity of P. nigrescens to bind transferrin
      was decreased when cells were grown in the presence of hemin. Preincubation of
      bacterial cells with hemin, hemoglobin, lactoferrin, fibrinogen, immunoglobulin
      G, or laminin did not affect transferrin-binding activity. The transferrin
      binding protein could be extracted from the cell surface of P. nigrescens by
      treatment with a zwitterionic detergent. Subjecting the cell surface extract to
      affinity chromatography on an agarose-transferrin column revealed that it
      contained a protein having an estimated molecular mass of 37 kDa and possessing
      transferrin-binding activity. The transferrin-binding activity of P. nigrescens
      and P. intermedia may permit the bacteria to obtain iron for survival and growth
      in periodontal pockets.

PMID- 9916062
TI  - Pathophysiology of antigen 85 in patients with active tuberculosis: antigen 85
      circulates as complexes with fibronectin and immunoglobulin G.
AB  - Antigen 85 (Ag85) complex proteins are major secretory products of Mycobacterium
      tuberculosis and induce strong cellular and humoral immune responses in infected
      experimental animals and human beings. We have previously shown that nanogram
      doses of these 30- to 32-kDa fibronectin-binding proteins inhibit local
      expression of delayed hypersensitivity by a T-cell fibronectin-dependent
      mechanism. Circulating levels of Ag85 might be expected to be elevated in
      patients with active tuberculosis and possibly to play a role in systemic anergy
      in these patients. To test this hypothesis, Ag85 was measured in serum and urine
      by a monoclonal antibody-based dot immunobinding assay in 56 patients and
      controls with known skin test reactivity. Median serum Ag85 levels were 50- to
      150-fold higher in patients with active tuberculosis than in patients with active
      M. avium-intracellulare disease or other nontuberculous pulmonary disease or in
      healthy controls (P < 0.001). The median and range of serum Ag85 in patients with
      active tuberculosis was not significantly different between skin test-positive
      and -negative subjects. Patients with active M. avium disease could be
      distinguished from those with disease due to M. tuberculosis by monoclonal anti
      Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were
      detected in any patient, regardless of the Ag85 level in serum. Chromatographic
      analysis and immunoprecipitation studies of serum revealed that Ag85 existed in
      the serum of these patients complexed to either fibronectin or immunoglobulin G
      (IgG). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20%
      of patients with active tuberculosis. In patients with active tuberculosis, Ag85
      is therefore likely to circulate primarily as complexes with plasma fibronectin
      and IgG rather than in unbound form. The existence of Ag85 complexes with plasma
      proteins would account for its lack of urinary clearance.

PMID- 9916063
TI  - Inhibition of Staphylococcus aureus adherence to collagen under dynamic
      conditions.
AB  - Staphylococcus aureus is the most common etiological agent of bacterial arthritis
      and acute osteomyelitis and has been shown to bind to type II collagen under
      static and dynamic conditions. We have previously reported the effect of shear on
      the adhesion of S. aureus Phillips to collagen and found that this process is
      shear dependent (Z. Li, M. Hook, J. M. Patti, and J. M. Ross, Ann. Biomed. Eng.
      24[Suppl. 1]:S-55). In this study, we used recombinant collagen adhesin fragments
      as well as polyclonal antibodies generated against adhesin fragments in attempts
      to inhibit bacterial adhesion. A parallel-plate flow chamber was used in a
      dynamic adhesion assay, and quantification of adhesion was accomplished by phase
      contrast video microscopy coupled with digital image processing. We report that
      both recombinant fragments studied, M19 and M55, and both polyclonal antibodies
      studied, alpha-M17 and alpha-M55, inhibit adhesion to varying degrees and that
      these processes are shear dependent. The M55 peptide and alpha-M55 cause much
      higher levels of inhibition than M19 and alpha-M17, respectively, at all wall
      shear rates studied. Our results demonstrate the importance of using a dynamic
      system in the assessment of inhibitory strategies and suggest the possible use of
      M55 and alpha-M55 in clinical applications to prevent infections caused by S.
      aureus adhesion to collagen.

PMID- 9916064
TI  - Tumor necrosis factor alpha receptor I is important for survival from
      Streptococcus pneumoniae infections.
AB  - Tumor necrosis factor alpha (TNF-alpha) is important in resistance to various
      microorganisms and provides signals to the target cells through two different
      receptors, TNF-alpha receptor I (TNFRI) (p55 receptor) and TNFRII (p75 receptor).
      To delineate the significance of the two different signaling pathways in
      resisting infections with extracellular bacteria, we examined the resistance of
      mice to Streptococcus pneumoniae (serotype 6B). TNF-alpha needs to be present
      early in infections, since one injection of wild-type mice with anti-TNF-alpha
      leads to an increased susceptibility of these mice to S. pneumoniae. TNF-alpha
      signaling through the p55 receptor (but not the p75 receptor) is crucial in
      resisting S. pneumoniae infections, because intraperitoneal injection of 100
      CFU/mouse killed p55-deficient mice by day 2 of infection, whereas 1,000,000
      CFU/mouse was needed to kill half of the control mice. p55-deficient mice do not
      show evidence of a deficient acute-phase response. All three types of mice (p55
      deficient, p75 deficient, and normal) showed comparable rises in the levels of
      two acute-phase proteins (serum amyloid P and C3) at 24, 48, and 72 h after the
      experimental infections, and all of the mice showed comparable influxes of
      neutrophils to the site of infection. Finally, it was demonstrated that p55
      deficient mice can be protected from the lethal effects of S. pneumoniae
      infection by injection of antibodies specific for S. pneumoniae polysaccharide
      capsule.

PMID- 9916066
TI  - Orchestration of neutrophil movement by intestinal epithelial cells in response
      to Salmonella typhimurium can be uncoupled from bacterial internalization.
AB  - Intestinal epithelial cells respond to Salmonella typhimurium by internalizing
      this pathogen and secreting, in a polarized manner, an array of chemokines which
      direct polymorphonuclear leukocyte (PMN) movement. Notably, interleukin-8 (IL-8)
      is secreted basolaterally and directs PMN through the lamina propria, whereas
      pathogen-elicited epithelial chemoattractant (PEEC) is secreted apically and
      directs PMN migration across the epithelial monolayer to the intestinal lumen.
      While most studies of S. typhimurium pathogenicity have focused on the mechanism
      by which this bacterium invades its host, the enteritis characteristically
      associated with salmonellosis appears to be more directly attributable to the PMN
      movement that occurs in response to this pathogen. Therefore, we sought to better
      understand the relationship between S. typhimurium invasion and epithelial
      promotion of PMN movement. First, we investigated whether S. typhimurium becoming
      intracellular was necessary or sufficient to induce epithelial promotion of PMN
      movement. Blocking S. typhimurium invasion by preventing, with cytochalasin D,
      the epithelial cytoskeletal rearrangements which mediate internalization did not
      reduce the epithelial promotion of PMN movement. Conversely, bacterial attainment
      of an intracellular position was not sufficient to induce model epithelia to
      direct PMN transmigration, since neither basolateral invasion by S. typhimurium
      nor apical internalization of an invasion-deficient mutant (achieved by inducing
      membrane ruffling with epidermal growth factor) induced this epithelial cell
      response. These results indicate that specific interactions between the apical
      surface of epithelial cells and S. typhimurium, rather than simply bacterial
      invasion, mediate the epithelial direction of PMN transmigration. To further
      investigate the means by which S. typhimurium induces epithelia to direct PMN
      movement, we investigated whether the same signaling pathways regulate secretion
      of IL-8 and PEEC. IL-8 secretion, but not PEEC secretion, was activated by
      phorbol myristate acetate and blocked by an inhibitor (mg-132) of the proteosome
      which mediates NF-kappabeta activation. Further, secretion of IL-8, but not PEEC,
      was activated by an entry-deficient (HilDelta) S. typhimurium mutant or by
      basolateral invasion of a wild-type strain. Together, these results indicate that
      distinct signaling pathways mediate S. typhimurium invasion, induction of IL-8
      secretion, and induction of PEEC secretion in model intestinal epithelia.

PMID- 9916065
TI  - Intracellular delivery of a cytolytic T-lymphocyte epitope peptide by pertussis
      toxin to major histocompatibility complex class I without involvement of the
      cytosolic class I antigen processing pathway.
AB  - A CD8(+) cytolytic T-lymphocyte (CTL) response to antigen-presenting cells
      generally requires intracellular delivery or synthesis of antigens in order to
      access the major histocompatibility complex (MHC) class I processing and
      presentation pathway. To test the ability of pertussis toxin (PT) to deliver
      peptides to the class I pathway for CTL recognition, we constructed fusions of
      CTL epitope peptides with a genetically detoxified derivative of PT (PT9K/129G).
      Two sites on the A (S1) subunit of PT9K/129G tolerated the insertion of peptides,
      allowing efficient assembly and secretion of the holotoxin fusion by Bordetella
      pertussis. Target cells incubated with these fusion proteins were specifically
      lysed by CTLs in vitro, and this activity was shown to be MHC class I restricted.
      The activity was inhibited by brefeldin A, suggesting a dependence on
      intracellular trafficking events, but was not inhibited by the proteasome
      inhibitors lactacystin and N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL).
      Furthermore, the activity was present in mutant antigen-presenting cells lacking
      the transporter associated with antigen processing, which transports peptides
      from the cytosol to the endoplasmic reticulum for association with MHC class I
      molecules. PT may therefore bypass the proteasome-dependent cytosolic pathway for
      antigen presentation and deliver epitopes to class I molecules via an alternative
      route.

PMID- 9916067
TI  - A controlled clinical study of the effect of nasal immunization with a
      Streptococcus mutans antigen alone or incorporated into liposomes on induction of
      immune responses.
AB  - Recent attention to mucosal immunization strategies has been focused on the nasal
      route for vaccine delivery. This study was designed to determine the
      effectiveness of a liposome-protein vaccine compared to that of a protein-only
      vaccine in inducing immune responses in humans. Healthy subjects were randomly
      assigned to two groups and immunized intranasally with a crude antigen
      preparation rich in glucosyltransferase (C-GTF) from Streptococcus mutans, alone
      or in liposomes. Parotid saliva, nasal wash, and serum were collected prior to
      and at weekly intervals following immunization and were analyzed for anti-C-GTF
      activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A
      (IgA) anti-C-GTF activity in the nasal wash from both groups after immunization
      increased to a mean peak of fivefold over the baseline level on day 28. Salivary
      IgA anti-C-GTF responses were induced to a lesser extent. IgG and IgA anti-C-GTF
      responses in serum were detected on day 14. The IgA responses were predominantly
      of the IgA1 subclass. These results show that C-GTF vaccines were more effective
      in inducing a local secretory IgA antibody response than a salivary or serum
      response when they were given intranasally. The IgA1 anti-C-GTF response in nasal
      wash samples for liposomal antigen versus antigen only was the only response
      which was significantly different (P < 0.04). This suggests that the form of the
      antigen affects the magnitude of the local mucosal response but not that of a
      disseminated response. These results provide evidence for the effective use of a
      nasal protein vaccine in humans for the induction of mucosal and systemic
      responses.

PMID- 9916068
TI  - The URA5 gene is necessary for histoplasma capsulatum growth during infection of
      mouse and human cells.
AB  - The Histoplasma capsulatum URA5 gene, which has recently been cloned and
      disrupted by allelic replacement, encodes orotidine-5'-monophosphate
      pyrophosphorylase. Inactivation of URA5 by either targeted or UV mutagenesis
      results in disruption of the pyrimidine biosynthetic pathway and uracil
      auxotrophy. We examined the effect of uracil auxotrophy due to a ura5 mutation on
      H. capsulatum virulence in both cell culture and whole-animal models. Uracil
      auxotrophs of two H. capsulatum restriction fragment length polymorphism classes
      were found to be avirulent in cultured murine and human cells, as well as in
      mice. Moreover, virulence could be restored either by supplying a functional URA5
      gene in trans or by supplying exogenous uracil during infection in vitro. These
      experiments demonstrate that the pyrimidine biosynthetic pathway is essential for
      H. capsulatum growth and virulence.

PMID- 9916070
TI  - Role of adult worm antigen-specific immunoglobulin E in acquired immunity to
      Schistosoma mansoni infection in baboons.
AB  - Allergic-type immune responses, particularly immunoglobulin E (IgE), correlate
      with protective immunity in human schistosomiasis. To better understand the
      mechanisms of parasite elimination we examined the immune correlates of
      protection in baboons (Papio cynocephalus anubis), which are natural hosts for
      Schistosoma mansoni and also develop allergic-type immunity with infection. In
      one experiment, animals were exposed to a single infection (1,000 cercariae) or
      were exposed multiple times (100 cercariae per week for 10 weeks) and
      subsequently were cured with praziquantel prior to challenge with 1, 000
      cercariae. Singly and multiply infected animals mounted 59 and 80% reductions in
      worm burden, respectively (P < 0.01). In a second experiment, animals were
      inoculated with S. mansoni ova and recombinant human interleukin 12 (IL-12). This
      produced a 37 to 39% reduction in adult worm burden after challenge (P < 0.05).
      Parasite-specific IgG, IgE, IgM, and peripheral blood cytokine production were
      evaluated. The only immune correlate of protection in both experiments was levels
      of soluble adult worm antigen (SWAP)-specific IgE in serum at the time of
      challenge infection and/or 6 weeks later. Baboons repeatedly infected with
      cercariae or immunized with ova and IL-12 developed two- to sixfold-greater
      levels of SWAP-specific IgE in serum than did controls, and this correlated with
      reductions in worm burden (r2, -0.40 to -0.64; P, <0. 01). Thus, in baboons and
      unlike mice, adult worm-specific IgE is uniquely associated with acquired
      immunity to S. mansoni infection. This similar association of parasite-specific
      IgE and protection among primates infected with schistosomiasis, along with
      similar pathology, anatomy, and genetic make-up, indicates that baboons provide
      an excellent permissive experimental model for better understanding the
      mechanisms of innate and acquired immunity to schistosomiasis in humans.

PMID- 9916069
TI  - Genetic vaccination against Coccidioides immitis: comparison of vaccine efficacy
      of recombinant antigen 2 and antigen 2 cDNA.
AB  - Previous studies from our laboratory established that C-ASWS, an alkali-soluble,
      water-soluble extract from cell walls of Coccidioides immitis, protects mice
      against lethal challenge with this fungus. The C-ASWS extract contains a
      glycosylated protein, designated antigen 2 (Ag2), and a polysaccharide antigen.
      We recently cloned Ag2 cDNA and showed that the recombinant fusion protein
      elicited strong delayed-type hypersensitivity responses in immunized mice. This
      investigation was undertaken to determine if the recombinant Ag2 protein,
      expressed as an Ag2-glutathione S-transferase (GST) fusion protein, or Ag2 cDNA
      would protect mice against lethal challenge with C. immitis. The recombinant Ag2
      GST protein protected BALB/c mice against intraperitoneal challenge with 250
      arthroconidia, as assessed by a decrease in fungal CFU in tissues. The Ag2-GST
      immunized mice did not show, however, an increased survival during a 30-day
      period postinfection. By contrast, immunization of mice with Ag2 cDNA ligated
      into the pVR1012 plasmid engendered protection against intraperitoneal challenge
      with 2,500 arthroconidia and against pulmonary challenge with 50 arthroconidia.
      Vaccine efficacy paralleled the development of delayed-type hypersensitivity
      responses to C. immitis antigen. Whereas mice vaccinated with the recombinant Ag2
      GST protein did not mount footpad hypersensitivity to C-ASWS or the recombinant
      Ag2-GST protein, mice vaccinated with the pVR1012-Ag2 construct mounted a strong
      footpad hypersensitivity and their spleen cells secreted gamma interferon upon in
      vitro stimulation with the Ag2-containing C-ASWS extract. This is the first
      investigation to show that genetic immunization can protect against lethal
      challenge with C. immitis.

PMID- 9916072
TI  - An in vitro tissue culture bilayer model to examine early events in Mycobacterium
      tuberculosis infection.
AB  - A tissue culture bilayer system that mimics some aspects of early alveolar
      infection by Mycobacterium tuberculosis was developed. This model incorporates
      human lung epithelial type II pneumocyte (A549) (upper chamber) and endothelial
      cell (lower chamber) layers separated by a microporous membrane. This
      construction makes it possible to observe and quantify the passage of bacteria
      through the two layers, to observe the interaction of the bacteria with the
      various cell types, and to examine the basic mechanisms of immune cell
      recruitment to the site of infection. After 10(7) organisms were added to the
      upper chamber we microscopically observed large numbers of bacteria attached to
      and within the pneumocytes and we determined by viable-cell counting that a small
      percentage of the inoculum (0.02 to 0.43%) passed through the bilayer into the
      lower chamber. When peripheral blood mononuclear cells were added to the lower
      chamber, microscopic examination indicated a migration of the mononuclear cells
      through the bilayer to the apical surface, where they were seen associated with
      the mycobacteria on the pneumocytes. The added complexity of the bilayer system
      offers an opportunity to define more precisely the roles of the various lung cell
      types in the pathogenesis of early tuberculosis.

PMID- 9916071
TI  - Neisseria gonorrhoeae mutants altered in toxicity to human fallopian tubes and
      molecular characterization of the genetic locus involved.
AB  - In an effort to identify potential cytotoxins expressed by Neisseria gonorrhoeae,
      we have identified a locus that, when mutated in the gonococcus, results in a
      significant increase in toxicity of the strain to human fallopian tube organ
      cultures (HFTOC). This locus, gly1, contains two open reading frames (ORFs) which
      are likely cotranscribed. ORF1 encodes a polypeptide of 17.8 kDa with a signal
      sequence that is recognized and processed in Escherichia coli and N. gonorrhoeae.
      The 15.6-kDa processed polypeptide has been observed in membrane fractions and
      filtered spent media from cultures of E. coli expressing gly1 and in outer
      membrane preparations of wild-type N. gonorrhoeae. The gly1 locus is not
      essential for bacterial survival, and it does not play a detectable role in
      epithelial cell adhesion, invasion, or intracellular survival. However, a gly1
      null mutant causes much more damage to fallopian tube tissues than its isogenic
      wild-type parent. A strain complemented in trans for the gly1 mutation showed a
      level of toxicity to HFTOC similar to the level elicited by the wild-type parent.
      Taken together, these results indicate an involvement of the gly1 locus in the
      toxicity of N. gonorrhoeae to human fallopian tubes.

PMID- 9916073
TI  - Induction of CD18-mediated passage of neutrophils by Pasteurella haemolytica in
      pulmonary bronchi and bronchioles.
AB  - Pasteurella haemolytica is an important respiratory pathogen of cattle that
      incites extensive infiltrates of neutrophils into the lung. In addition to the
      parenchymal damage caused by factors released by P. haemolytica, neutrophils
      contribute to the pathologic changes in the lungs. Molecules which mediate
      neutrophil infiltration into the lungs during P. haemolytica pneumonia are poorly
      characterized. To determine whether the CD18 family (beta2-integrin) of leukocyte
      adhesion molecules mediates initial passage of neutrophils into the pulmonary
      bronchi and bronchioles of lungs infected with P. haemolytica, three Holstein
      calves homozygous for bovine leukocyte adhesion deficiency (BLAD) (CD18-deficient
      neutrophils), and three age- and breed-matched control calves (normal CD18
      expression) were inoculated with P. haemolytica A1 via a fiberoptic bronchoscope
      and euthanized at 2 h postinoculation. Sections of lung were stained for
      neutrophils, and the intensity of neutrophilic infiltration was determined by
      computerized image analysis. Significantly fewer (P < 0.05) neutrophils
      infiltrated the lumen, epithelium, and adventitia of bronchioles and bronchi in
      lungs of calves with BLAD compared to normal calves, which had dense infiltrates
      within these sites at 2 h postinoculation. The reduced infiltration in calves
      with BLAD occurred despite the presence of an extremely large number of
      neutrophils in peripheral blood that is typical for these calves. The large
      number of neutrophils in the blood of calves with BLAD is probably a physiologic
      response that can occur without microbial colonization, since one calf with BLAD
      that was raised under germ-free conditions had large numbers of neutrophils in
      the blood that were similar to those in a calf with BLAD that was raised
      conventionally. Neutrophil counts in the germ-free and conventionally reared
      calves with BLAD were much higher than those in the three normal calves raised
      under germ-free conditions. The work in this study demonstrates that during the
      initial inflammatory response, neutrophils with normal CD18 expression pass more
      readily than CD18-deficient neutrophils into the walls and lumen of bronchi and
      bronchioles. It suggests that CD18 is needed for initial passage through the
      extensive extracellular matrix of the bronchi and bronchioles. This has potential
      importance for the development of therapies to direct or inhibit neutrophil
      infiltration into conducting airways rather than alveolar spaces.

PMID- 9916074
TI  - Surface antigen exposure by bismuth dimercaprol suppression of Klebsiella
      pneumoniae capsular polysaccharide.
AB  - The bacterial capsule is an important virulence determinant in animal and plant
      disease. Bacterial capsule and slime can be inhibited by bismuth compounds,
      especially when complexed with lipophilic thiol chelators. Bismuth dimercaprol
      (BisBAL) at 1 ppm of Bi3+ repressed Klebsiella pneumoniae capsule expression in
      defined medium by nearly 90%, which exposed subsurface structures. The phagocytic
      index for BisBAL-treated bacteria increased from <10 to 360 bacteria per 100
      neutrophils in the presence of complement and anticapsular or anti-O antigen
      antiserum. BisBAL treatment also enhanced the reactivity of monoclonal antibodies
      (MAbs) specific for the O1-antigen lipopolysaccharide (LPS) or the LPS core in a
      dose-dependent manner as indicated by the results of enzyme-linked immunosorbent
      assays. When anti-O1 MAb was used, the reactivity increased significantly for
      fully encapsulated O1:K1 or O1:K2 cells but not for O1:K- cells. Deposition of
      C3b also increased significantly for BisBAL-treated O1:K1 or O1:K2 cells but not
      for O1:K- cells. Survival of a serum-sensitive strain was <0.1% when nonimmune
      human serum absorbed with O1:K1 cells was used and 107% when BisBAL-treated cells
      were used for absorption. Outer membrane proteins were also more accessible on
      the surface of K. pneumoniae after BisBAL treatment. Thus, at subinhibitory
      levels, BisBAL inhibited capsule expression, which promoted phagocytosis,
      enhanced the reactivity of specific antibodies for LPS O antigen, LPS core
      epitopes, or outer-membrane proteins, and enhanced complement interaction with
      encapsulated K. pneumoniae. By unmasking bacterial surface structures and
      enhancing the immune system reactivity to bacteria, bismuth thiols may prove
      useful as adjuncts for vaccination.

PMID- 9916075
TI  - Early resistance of interleukin-10 knockout mice to acute systemic candidiasis.
AB  - In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO)
      mice eliminated an experimental intravenous inoculation with Candida albicans
      from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10
      KO mice was evident at 24 h after intravenous challenge with the fungus.
      Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible
      to systemic candidiasis than were immunocompetent controls. The hyperresistance
      of IL-10 KO mice to acute systemic candidiasis did not seem to correlate with
      nitric oxide-mediated immunity, but rather, it appeared to be associated with
      more efficient effector function of innate cells, possibly neutrophils. In
      support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice
      were more efficient at killing C. albicans blastoconidia and hyphae than were
      neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice
      that were monoassociated with C. albicans for 4 weeks showed any histologic
      evidence of systemic candidiasis of endogenous origin. In contrast to systemic
      candidiasis, we observed no significant (P < 0.05) differences in susceptibility
      among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric
      candidiasis. Our results suggest that IL-10 exerts a negative effect on the
      early, innate response to acute systemic candidiasis; however, in comparison to
      immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency
      enhanced susceptibility to orogastric candidiasis.

PMID- 9916076
TI  - Protective immunization with a novel membrane protein of Plasmodium yoelii
      infected erythrocytes.
AB  - Immunization with a particulate fraction of blood-stage antigens was shown
      previously to protect mice against Plasmodium yoelii malaria. To identify
      antigens inducing the protective response, sera from immunized mice were used to
      screen a P. yoelii cDNA expression library. Sequence analysis of one 2.6-kb cDNA
      clone indicated that the identified gene, pypag-1, encoded a novel plasmodial
      antigen. Two nonoverlapping regions of pypag-1 were expressed in Escherichia
      coli. The first recombinant antigen, pAg-1N, contained the N-terminal 337
      residues, which included a putative transmembrane domain and a region relatively
      rich in tryptophan residues. The second recombinant antigen, pAg-1C, contained
      the remaining C-terminal 211 residues, which included 31 copies of a 5-amino-acid
      degenerative repeat. Immunoblot studies using rabbit antiserum raised against
      recombinant pAg-1N showed that the native pypAg-1 protein migrated at
      approximately 98 kDa, considerably slower than its predicted molecular mass of 66
      kDa. Immunofluorescence studies localized the expression of the native pypAg-1
      protein both to the cytoplasm and at the surface of P. yoelii-infected
      erythrocytes. Immunization with either pAg-1N or pAg-1C induced a four- to
      sevenfold reduction in P. yoelii blood-stage parasitemia. As such, pypAg-1
      appears to contain at least two distinct protective epitopes. To our knowledge,
      this is the first characterization of a protective antigen of P. yoelii that is
      associated with the erythrocyte membrane.

PMID- 9916077
TI  - Use of an isogenic mutant constructed in Moraxella catarrhalis To identify a
      protective epitope of outer membrane protein B1 defined by monoclonal antibody
      11C6.
AB  - Moraxella catarrhalis-induced otitis media continues to be a significant cause of
      infection in young children, prompting increased efforts at identifying effective
      vaccine antigens. We have previously demonstrated that M. catarrhalis expresses
      specific outer membrane proteins (OMPs) in response to iron limitation and that
      this organism can utilize transferrin and lactoferrin for in vitro growth. One of
      these proteins, which binds human transferrin, is OMP B1. As the human host
      presents a naturally iron-limited environment, proteins, like OMP B1, which are
      expressed in response to this nutritional stress are potential vaccine antigens.
      In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to
      a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This
      antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is
      the M. catarrhalis homologue to the transferrin binding protein B described for
      pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus
      pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the
      surface of Escherichia coli confers transferrin binding activity, confirming that
      this protein is likely involved in iron acquisition. In addition, ompB1 was used
      to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed
      7169b12, was used as the control in bactericidal assays designed to determine if
      OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human
      complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the
      ompB1 isogenic mutant was resistant to this bactericidal activity. Further
      analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the
      clinical isolates tested. These data suggest that OMP B1 is a potential vaccine
      antigen against M. catarrhalis infections.

PMID- 9916078
TI  - Involvement of mitogen-activated protein kinase pathways in interleukin-8
      production by human monocytes and polymorphonuclear cells stimulated with
      lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins.
AB  - Interleukin-8 (IL-8) is a chemokine that belongs to the alpha-chemokine or CXC
      subfamily and is produced by a wide variety of human cells, including monocytes
      and polymorphonuclear cells (PMN). IL-8 is secreted in response to inflammatory
      stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little
      is known about the mechanisms by which these agents mediate IL-8 induction. In
      this report, we show that Mycoplasma fermentans lipid-associated membrane
      proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human
      monocyte) cells and PMN at the same extent as LPS. It was previously demonstrated
      that stimulation of monocytic cells with either LPS or LAMPf led to a series of
      common downstream signaling events, including the activation of protein tyrosine
      kinase and of mitogen-activated protein kinase cascades. By using PD-98059 and
      SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of
      ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38
      cascades play a key role in the production of IL-8 by monocytes and PMN
      stimulated with bacterial fractions.

PMID- 9916079
TI  - Characterization of a novel methyl-accepting chemotaxis gene, dmcB, from the oral
      spirochete Treponema denticola.
AB  - Immediately downstream from the previously isolated Treponema denticola ATCC
      35405 prtB gene coding for a chymotrypsinlike protease activity, an open reading
      frame, ORF3, was identified which shared significant homology with the highly
      conserved domains (HCDs) of bacterial methyl-accepting chemotaxis proteins
      (MCPs). Nucleotide sequencing of this ORF revealed that the gene would code for a
      protein with a size of approximately 41 kDa. In addition, this sequence contained
      a domain which was virtually identical to the HCD of a recently characterized
      MCP, DmcA, of strain 35405. Therefore, this ORF was named dmcB. Northern blot
      analysis suggested that dmcB was part of an operon structure containing prtB.
      Insertional inactivation of dmcB utilizing an ermF-ermAM cassette resulted in a
      mutant with decreased chemoattraction toward nutrient supplements. In addition,
      the mutant displayed an altered pattern of methylated proteins under conditions
      of chemotaxis. Inactivation of the dmcB gene also attenuated the methylation of
      the DmcA protein. These results suggest that the dmcB gene codes for an MCP in T.
      denticola which may interact with other MCPs in these organisms.

PMID- 9916080
TI  - Characterization of candidate live oral Salmonella typhi vaccine strains
      harboring defined mutations in aroA, aroC, and htrA.
AB  - The properties of two candidate Salmonella typhi-based live oral typhoid vaccine
      strains, BRD691 (S. typhi Ty2 harboring mutations in aroA and aroC) and BRD1116
      (S. typhi Ty2 harboring mutations in aroA, aroC, and htrA), were compared in a
      number of in vitro and in vivo assays. BRD1116 exhibited an increased
      susceptibility to oxidative stress compared with BRD691, but both strains were
      equally resistant to heat shock. Both strains showed a similar ability to invade
      Caco-2 and HT-29 epithelial cells and U937 macrophage-like cells, but BRD1116 was
      less efficient at surviving in epithelial cells than BRD691. BRD1116 and BRD691
      were equally susceptible to intracellular killing within U937 cells. Similar
      findings were demonstrated in vivo, with BRD1116 being less able to survive and
      translocate to secondary sites of infection when inoculated into the lumen of
      human intestinal xenografts in SCID mice. However, translocation of BRD1116 to
      spleens and livers in SCID mice occurred as efficiently as that of BRD691 when
      inoculated intraperitonally. The ability of BRD1116 to increase the secretion of
      interleukin-8 following infection of HT-29 epithelial cells was comparable to
      that of BRD691. Therefore, loss of the HtrA protease in S. typhi does not seem to
      alter its ability to invade epithelial cells or macrophages or to induce
      proinflammatory cytokines such as IL-8 but significantly reduces intracellular
      survival in human intestinal epithelial cells in vitro and in vivo.

PMID- 9916081
TI  - YopJ of Yersinia spp. is sufficient to cause downregulation of multiple mitogen
      activated protein kinases in eukaryotic cells.
AB  - Pathogenic Yersinia spp. utilize a plasmid-encoded type III secretion system to
      deliver a set of Yop effector proteins into eukaryotic cells. Previous studies
      have shown that the effector YopJ is required for Yersinia to cause
      downregulation of the mitogen-activated protein (MAP) kinases c-Jun N-terminal
      kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1 and 2 in
      infected macrophages. Here we demonstrate that YopJ is sufficient to cause
      downregulation of multiple MAP kinases in eukaryotic cells. Cellular
      fractionation experiments confirmed that YopJ is delivered into the cytoplasmic
      fraction of macrophages by the type III system. Production of YopJ in COS-1 cells
      by transfection significantly reduced (5- to 10-fold) activation of JNK, p38, and
      ERK in response to several different stimuli, including serum and tumor necrosis
      factor alpha. JNK activation mediated by RacV12, an activated mutant of Rac1, was
      also blocked by YopJ in COS-1 cells, indicating that YopJ acts downstream of this
      small GTPase to downregulate MAP kinase signaling. Analysis of transfected COS-1
      cells by immunofluorescence microscopy revealed that YopJ is recruited from the
      cytoplasmic compartment to the cell periphery in response to stimuli (e.g.,
      serum) that induce membrane ruffling. These data indicate that YopJ functions as
      a "MAP kinase toxin" to selectively block nuclear responses that are triggered by
      Yersinia-host cell interaction.

PMID- 9916082
TI  - The R-type pyocin of Pseudomonas aeruginosa C is a bacteriophage tail-like
      particle that contains single-stranded DNA.
AB  - Pseudomonas aeruginosa R-type pyocin particles have been described as
      bacteriocins that resemble bacteriophage tail-like structures. Because of their
      unusual structure, we reexamined whether they contained nucleic acids. Our data
      indicated that pyocin particles isolated from P. aeruginosa C (pyocin C) contain
      DNA. Probes generated from this DNA by the random-primer extension method
      hybridized to distinct bands in restriction endonuclease-digested P. aeruginosa C
      genomic DNA. These probes also hybridized to genomic DNA from 6 of 18 P.
      aeruginosa strains that produced R-type pyocins. Asymmetric PCR, complementary
      oligonucleotide hybridization, and electron microscopy indicated that pyocin C
      particles contained closed circular single-stranded DNA, approximately 4.0 kb in
      length. Examination of total intracellular DNA from mitomycin C-induced cultures
      revealed the presence of two extrachromosomal DNA molecules, a double-stranded
      molecule and a single-stranded molecule, which hybridized to pyocin DNA. Sequence
      analysis of 7,480 nucleotides of P. aeruginosa C chromosomal DNA containing the
      pyocin DNA indicated the presence of pyocin open reading frames with similarities
      to open reading frames from filamentous phages and cryptic phage elements. We did
      not observe any similarities to known phage structural proteins or previously
      characterized pseudomonal prt genes expressing R-type pyocin structural proteins.
      These studies demonstrate that pyocin particles from P. aeruginosa C are
      defective phages that contain a novel closed circular single-stranded DNA and
      that this DNA was derived from the chromosome of P. aeruginosa C.

PMID- 9916083
TI  - Monocytes that have ingested Yersinia enterocolitica serotype O:3 acquire
      enhanced capacity to bind to nonstimulated vascular endothelial cells via P
      selectin.
AB  - Reactive arthritis is usually a self-limiting polyarthritis which develops after
      certain gastrointestinal or urogenital infections. Microbial antigens found in
      the inflamed joints are thought to play a key role in the development of this
      disease. It is not known how antigens of the pathogenic organisms migrate from
      the mucosal tissues into the joints. The data presented here show that
      mononuclear phagocytes which mediate the dissemination of several intracellular
      pathogens acquire an enhanced capacity to bind to nonstimulated vascular
      endothelial cells after phagocytosis of Yersinia enterocolitica O:3, one of the
      causative organisms of reactive arthritis. The increased binding to previously
      nonstimulated endothelial cells was mediated by P-selectin, whose translocation
      to the endothelial cell surface was induced by monocytes with intracellular
      Yersinia bacteria. These results suggest that mononuclear phagocytes may be
      responsible for the dissemination of bacterial antigens and the initiation of the
      joint inflammation in reactive arthritis.

PMID- 9916084
TI  - Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in
      Kenya: evidence for rare and prevalent variants.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is the name given
      to a family of parasite proteins that are inserted into the infected erythrocyte
      surface. Studies using agglutination assays have shown previously that PfEMP1
      epitopes are extremely diverse. In a study in Kenya, 21 parasite isolates,
      including nine from children with severe malaria, were tested for agglutination
      by 33 pairs of plasma, 21 of which were from the corresponding children. Each
      plasma pair consisted of a sample taken at the time of disease (acute) and one
      taken 3 weeks later (convalescent). In agreement with previous studies, infection
      was generally followed by the induction of antibodies specific to the homologous
      parasite isolate. In addition however, the results show that (i) some isolates
      were agglutinated very frequently by heterologous plasma; (ii) unexpectedly,
      these frequently agglutinated isolates tended to be from individuals with severe
      malaria; (iii) an inverse relationship existed between the agglutination
      frequency of each parasite isolate in heterologous plasma and the agglutinating
      antibody repertoire of the homologous child at the time of disease; and (iv) A 3
      month-old child apparently still carrying maternal antibodies was infected by a
      rarely agglutinated isolate. This child's plasma agglutinated all isolates at the
      time of disease, apart from the homologous isolate. These results support the
      idea that preexisting anti-PfEMP1 antibodies can select the variants that are
      expressed during a new infection and may suggest the existence of a dominant
      subset of PfEMP1 variants.

PMID- 9916085
TI  - Impact of the high-affinity proline permease gene (putP) on the virulence of
      Staphylococcus aureus in experimental endocarditis.
AB  - Staphylococcus aureus causes a wide variety of invasive human infections.
      However, delineation of the genes which are essential for the in vivo survival of
      this pathogen has not been accomplished to date. Using signature tag mutagenesis
      techniques and large mutant pool screens, previous investigators identified
      several major gene classes as candidate essential gene loci for in vivo survival;
      these include genes for amino acid transporters, oligopeptide transporters, and
      lantibiotic synthesis (W. R. Schwan, S. N. Coulter, E. Y. W. Ng, M. H. Langhorne,
      H. D. Ritchie, L. L. Brody, S. Westbrock-Wadman, A. S. Bayer, K. R. Folger, and
      C. K. Stover, Infect. Immun. 66:567-572, 1998). In this study, we directly
      compared the virulence of four such isogenic signature tag mutants with that of
      the parental strain (RN6390) by using a prototypical model of invasive S. aureus
      infection, experimental endocarditis (IE). The oligonucleotide signature tag
      (OST) mutant with insertional inactivation of the gene (putP) which encodes the
      high-affinity transporter for proline uptake exhibited significantly reduced
      virulence in the IE model across three challenge inocula (10(4) to 10(6) CFU) in
      terms of achievable intravegetation densities (P, <0.05). The negative impact of
      putP inactivation on in vivo survival in the IE model was confirmed by
      simultaneous challenge with the original putP mutant and the parental strain as
      well as by challenge with a putP mutant in which this genetic inactivation was
      transduced into a distinct parental strain (S6C). In contrast, inactivation of
      loci encoding an oligopeptide transporter, a purine repressor, and lantibiotic
      biosynthesis had no substantial impact on the capacity of OST mutants to survive
      within IE vegetations. Thus, genes encoding the uptake of essential amino acids
      may well represent novel targets for new drug development. These data also
      confirm the utility of the OST technique as an important screening methodology
      for identifying candidate genes as requisite loci for the in vivo survival of S.
      aureus.

PMID- 9916086
TI  - Increased type 1 fimbrial expression among commensal Escherichia coli isolates in
      the murine cecum following catabolic stress.
AB  - Although indigenous bacteria intimately colonize the intestinal mucosa, under
      normal conditions the intestinal epithelial cell is free of adherent bacteria.
      Nonetheless, commensal bacteria such as Escherichia coli adhere to and
      translocate across the intestinal epithelium in association with a number of
      pathologic states including hemorrhagic shock, immunosuppression, traumatic
      tissue injury, and lack of enteral feedings. The adhesins involved in the
      adherence of indigenous E. coli to the intestinal epithelium in vivo following
      catabolic stress are unknown. We have developed a mouse model to study the
      bacterial adhesins which mediate the increased intestinal adherence of E. coli
      after partial hepatectomy and short-term starvation. Our studies demonstrated
      that hepatectomy and starvation in the mouse were associated with a 7,500-fold
      increase in the numbers of E. coli bacteria adhering to the cecum. In addition,
      erythrocyte agglutination studies, as well as immunostaining of fimbrial
      preparations and electron micrographs of the bacteria, revealed that surface type
      1 fimbriae were more abundant in the commensal E. coli harvested from the ceca of
      the stressed mice. These E. coli isolates adhered to a mouse colon cell line and
      injected cecal loops in a mannose-inhibitable manner, which suggests a role for
      type 1 fimbriae in the adherence of the E. coli isolates to the cecum in vivo
      following host catabolic stress.

PMID- 9916087
TI  - Identification and characterization of PtlC, an essential component of the
      pertussis toxin secretion system.
AB  - PtlC is a member of a set of proteins necessary for the secretion of pertussis
      toxin (PT) from Bordetella pertussis. Using polyclonal antibodies specific for
      PtlC, we identified PtlC as a protein with an apparent molecular weight of 85,000
      that localizes to the membrane fraction of bacterial cell extracts. We found that
      a mutant strain of B. pertussis that contains an in-frame deletion in ptlC is
      unable to secrete PT and that PT secretion is fully restored by expressing ptlC
      in trans, indicating that PtlC is essential for transport of PT across the
      bacterial membrane(s). PT secretion was inhibited in wild-type B. pertussis after
      introduction of a plasmid expressing a mutant ptlC altered in the putative
      nucleotide-binding region, suggesting that this region of PtlC is essential for
      proper function. Moreover, the observed dominant negative phenotype suggests that
      PtlC either functions as a multimer or interacts with some other component(s)
      necessary for secretion of PT.

PMID- 9916089
TI  - Characterization of the avian pathogenic Escherichia coli hemagglutinin Tsh, a
      member of the immunoglobulin A protease-type family of autotransporters.
AB  - We reported earlier that a single gene, tsh, isolated from a strain of avian
      pathogenic Escherichia coli (APEC) was sufficient to confer on E. coli K-12 a
      hemagglutinin-positive phenotype and that the deduced sequence of the Tsh protein
      shared homology to the serine-type immunoglobulin A (IgA) proteases of Neisseria
      gonorrhoeae and Haemophilus influenzae. In this report we show that E. coli K-12
      containing the recombinant tsh gene produced two proteins, a 106-kDa
      extracellular protein and a 33-kDa outer membrane protein, and was also able to
      agglutinate chicken erythrocytes. N-terminal sequence data indicated that the 106
      kDa protein, designated Tshs, was derived from the N-terminal end of Tsh after
      the removal of a 52-amino-acid N-terminal signal peptide, while the 33-kDa
      protein, designated Tshbeta, was derived from the C-terminal end of Tsh starting
      at residue N1101. The Tshs domain contains the 7-amino-acid serine protease motif
      that includes the active-site serine (S259), found also in the secreted domains
      of the IgA proteases. However, site-directed mutagenesis of S259 did not abolish
      the hemagglutinin activity or the extracellular secretion of Tshs indicating that
      host-directed proteolysis was mediating the release of Tshs. Studies with an E.
      coli K-12 ompT mutant strain showed that the surface protease OmpT was not needed
      for the secretion of Tshs. Tsh belongs to a subclass of the IgA protease family,
      which also includes EspC of enteropathogenic E. coli, EspP of enterohemorragic E.
      coli, and SepA and VirG of Shigella flexneri, which seem to involve a host
      endopeptidase to achieve extracellular release of their N-terminal domains. In
      proteolytic studies conducted in vitro, Tshs did not cleave the substrate of the
      IgA proteases, human IgA1 or chicken IgA, and did not show proteolytic activity
      in a casein-based assay. Correlation of Tsh expression and hemagglutination
      activity appears to be a very complex phenomenon, influenced by strain and
      environmental conditions. Nevertheless, for both APEC and recombinant E. coli K
      12 strains containing the tsh gene, it was only the whole bacterial cells and not
      the cell-free supernatants that could confer hemagglutinin activity. Our results
      provide insights into the expression, secretion, and proteolytic features of the
      Tsh protein, which belongs to the growing family of gram-negative bacterial
      extracellular virulence factors, named autotransporters, which utilize a self
      mediated mechanism to achieve export across the bacterial cell envelope.

PMID- 9916088
TI  - Differential posttranslational processing confers intraspecies variation of a
      major surface lipoprotein and a macrophage-activating lipopeptide of Mycoplasma
      fermentans.
AB  - The malp gene of Mycoplasma fermentans is shown to occur in single copy but to
      encode two discrete translated forms of lipid-modified surface protein that can
      be differentially expressed on isolates within this species: MALP-2, a 14-amino
      acid (2-kDa) lipopeptide with potent macrophage-stimulatory activity (P. F.
      Muhlradt, M. Kiess, H. Meyer, R. Sussmuth, and G. Jung, J. Exp. Med. 185:1951
      1958, 1997), and MALP-404, an abundant, full-length (404-amino-acid) surface
      lipoprotein of 41 kDa, previously designated P41 (K. S. Wise, M. F. Kim, P. M.
      Theiss, and S.-C. Lo, Infect. Immun. 61:3327-3333, 1993). The sequences,
      transcripts, and translation products of malp were compared between clonal
      isolates of strains PG18 (known to express P41) and II-29/1 (known to express
      high levels of MALP-2). Despite conserved malp DNA sequences containing full
      length open reading frames and expression of full-length monocistronic
      transcripts in both isolates, Western blotting using a monoclonal antibody (MAb)
      to the N-terminal MALP-2 peptide revealed marked differences in the protein
      products expressed. Whereas PG18 expressed abundant MALP-404 with detectable MALP
      2, II-29/1 revealed no MALP-404 even in samples containing a large comparative
      excess of MALP-2. Colony immunoblots with the MAb showed uniform surface
      expression of MALP-2 in II-29/1 populations. A second MAb to an epitope of MALP
      404 outside the MALP-2 sequence predictably failed to stain II-29/1 colonies but
      uniformly stained PG18 populations. Collectively, these results provide evidence
      for novel posttranscriptional (probably posttranslational) processing pathways
      leading to differential intraspecies expression of a major lipoprotein, and a
      potent macrophage-activating lipopeptide, on the surface of M. fermentans. In the
      course of this study, a striking conserved motif (consensus, TD-G--DDKSFNQSAWE-
      ), designated SLA, was identified in MALP-404; this motif is also distributed
      among selected lipoproteins and species from diverse bacterial genera, including
      Bacillus, Borrelia, Listeria, Mycoplasma, and Treponema. In addition, malp was
      shown to flank a chromosomal polymorphism. In eight isolates of M. fermentans
      examined, malp occurred upstream of an operon encoding the phase-variable P78 ABC
      transporter; but, in three of these isolates, a newly discovered insertion
      sequence, IS1630 (of the IS30 class), was located between these genes.

PMID- 9916090
TI  - Strategy for cross-protection among Shigella flexneri serotypes.
AB  - Based upon the lipopolysaccharide (LPS) structure and antigenicity of Shigella
      group B, a strategy for broad cross-protection against 14 Shigella flexneri
      serotypes was designed. This strategy involves the use of two S. flexneri
      serotypes (2a and 3a), which together bear the all of the major antigenic group
      factors of this group. The novel attenuated strains used in these studies were S.
      flexneri 2a strain CVD 1207 (DeltaguaB-A DeltavirG Deltaset1 Deltasen) and S.
      flexneri 3a strain CVD 1211 (DeltaguaB-A DeltavirG Deltasen). Guinea pigs were
      immunized with an equal mixture of these strains and later challenged (Sereny
      test) with a wild-type S. flexneri serotype 1a, 1b, 2b, 4b, 5b, Y, or 6 strain of
      demonstrated virulence in the same model. Guinea pigs that were immunized with
      these two vaccine strains produced serum and mucosal antibodies that cross
      reacted with all the S. flexneri serotypes tested (except of S. flexneri serotype
      6) as assessed by enzyme-linked immunosorbent assay, immunoblotting, and slide
      agglutination. Furthermore, the combination vaccine conferred significant
      protection against challenge with S. flexneri serotypes 1b, 2b, 5b, and Y but not
      with serotypes 1a, 4b, or (as predicted) 6.

PMID- 9916091
TI  - Regulatory T cells in the antibody response to Haemophilus influenzae type b
      polysaccharide.
AB  - An in vitro culture system for the induction of an antipolysaccharide response
      was used to study the cellular interactions which determine the magnitude and
      nature of this B-lymphocyte response. Healthy adult volunteers were vaccinated
      with the Haemophilus influenzae type b polysaccharide (PRP)-tetanus toxoid (TT)
      conjugate vaccine. Optimal in vitro anti-PRP and anti-TT antibody responses were
      obtained when B cells were cultured with equal amounts of T cells. The in vitro
      response is antigen dependent and antigen specific. Culturing with PRP mixed with
      TT in the presence of T cells induces the highest number of anti-PRP antibody
      secreting cells (ASC) (128.4 x// 15.9 [geometric mean x// standard deviation]
      immunoglobulin M [IgM] anti-PRP ASC/10(6) cells; 9.3 x// 7.6 IgG anti-PRP
      ASC/10(6) cells). Culturing without T cells induced no anti-PRP ASC; culturing
      with only PRP, in the presence of T cells, yielded low numbers of anti-PRP ASC
      (3.7 x// 5.2 IgM anti-PRP ASC/10(6) cells and 1.2 x// 2.2 IgG anti-PRP ASC/10(6)
      cells). Transwell studies showed that the requirements for the antibody response
      against the polysaccharide are different from those of an antiprotein response.
      Cytokines formed as a consequence of contact between protein-specific B and T
      cells were on their own not sufficient to activate TT-specific B cells (8.4 x//
      1.4 anti-TT ASC/10(6) cells); direct contact between T and B cells appeared to be
      an absolute requirement. However, physical contact between B and T cells in one
      compartment of the Transwell system resulted in the release of soluble factors
      able to stimulate B cells in the other compartment to secrete antipolysaccharide
      antibodies (164 x// 1.6 anti-PRP ASC/10(6) cells).

PMID- 9916092
TI  - Cholera toxin B subunit activates arachidonic acid metabolism.
AB  - Cholera toxin (CT) increases intestinal secretion of water and electrolytes and
      modulates the mucosal immune response by stimulating cellular synthesis of
      arachidonic acid (AA) metabolites (e.g., prostaglandin E2), as well as the
      intracellular second messenger cyclic AMP (cAMP). While much is known about the
      mechanism of CT stimulation of adenylate cyclase, the toxin's activation of
      phospholipase A2, which results in increased hydrolysis of AA from membrane
      phospholipids, is not well understood. To determine whether CT activation of AA
      metabolism requires CT's known enzymatic activity (i.e., ADP-ribosylation of
      GSalpha), we used native CT and a mutant CT protein (CT-2*) lacking ADP-ribose
      transferase activity in combination with S49 wild-type (WT) and S49 cyc- murine
      Theta (Th)1.2-positive lymphoma cells deficient in GSalpha. The experimental
      results showed that native CT stimulated the release of [3H[AA from S49 cyc-
      cells at a level similar to that for S49 WT cells, indicating that GSalpha is not
      essential for this process. Further, levels of cAMP in the CT-treated cyc- cells
      remained the same as those in the untreated control cells. The ADP
      ribosyltransferase-deficient CT-2* protein, which was incapable of increasing
      synthesis of cAMP, displayed about the same capacity as CT to evoke the release
      of [3H]AA metabolites from both S49 WT and cyc- cells. We concluded that
      stimulation of arachidonate metabolism in S49 murine lymphoma cells by native CT
      does not require enzymatically functional CT, capable of catalyzing the ADP
      ribosylation reaction. These results demonstrated for the first time that
      stimulation of adenylate cyclase by CT and stimulation of AA metabolism by CT are
      not necessarily coregulated. In addition, the B subunits purified from native CT
      and CT-2* both simulated the release of [3H]AA from S49 cyc- cells and murine
      monocyte/macrophage cells (RAW 264.7), suggesting a receptor-mediated cell
      activation process of potential importance in enhancing immune responses to
      vaccine components.

PMID- 9916093
TI  - Bacterial invasion is not required for activation of NF-kappaB in enterocytes.
AB  - Pathogenic enteric microorganisms induce the NF-kappaB-dependent expression of
      proinflammatory genes in intestinal epithelial cells. The purpose of the present
      study was to clarify the contribution of microbial invasion to the degradation of
      the regulatory protein Ikappa Balpha and the subsequent activation of NF-kappaB
      in cultured intestinal epithelial cells. Caco-2BBe cells were incubated with
      Salmonella dublin, Salmonella typhimurium, or a weakly invasive strain of E.
      coli. S. dublin and S. typhimurium (10(7) organisms/ml) induced equivalent
      concentration-dependent gel mobility shifts of an NF-kappaB consensus sequence
      that was preceded by Ikappa Balpha degradation. E. coli (10(7) organisms/ml) did
      not induce Ikappa Balpha degradation or NF-kappaB translocation. Pretreatment
      with cytochalasin D blocked invasion of all three strains but had no effect on
      Ikappa Balpha degradation or NF-kappaB activation. S. dublin and S. typhimurium
      adhered to Caco-2BBe cells 3- to 10-fold more than E. coli. NF-kappaB activation
      was prevented by physical separation of S. dublin from Caco-2BBe cells by a 0. 4
      micrometers-pore-size filter. Our results imply that bacterial adhesion, rather
      than invasion or release of a secreted factor, is sufficient to induce
      IkappaBalpha degradation and NF-kappaB activation in intestinal epithelial cells.
      Our data suggest that strategies to reduce enteric inflammation should be
      directed to the reduction of bacterial enterocyte adhesion.

PMID- 9916094
TI  - Intranasal immunization confers protection against murine Pneumocystis carinii
      lung infection.
AB  - To evaluate the feasibility of mucosal immunization against Pneumocystis carinii
      (Pc) experimental infection, female BALB/c mice were intranasally immunized three
      times with soluble Pc antigens plus cholera toxin fraction B (Pc-CTB); control
      groups received either Pc antigen, CTB, or phosphate-buffered saline (PBS) alone.
      Two weeks after the last immunization, five animals from each group were
      sacrificed, and cellular and humoral immune responses were evaluated. The
      remaining five mice were CD4 depleted using a monoclonal antibody against mouse
      CD4 and inoculated with viable Pc. Significantly higher specific
      lymphoproliferative responses from tracheobronchial lymph node cells,
      immunoglobulin M (IgM) and IgG antibody levels in serum, and bronchoalveolar
      lavage (BAL)-derived IgA antibody concentrations were observed in the Pc-CTB
      group of mice relative to control groups (P < 0.01). Five weeks after challenge,
      no Pc organisms were observed in the lung smears of the Pc-CTB group, while the
      animals receiving antigen, adjuvant, or PBS had progressively higher numbers of
      Pc microorganisms. By Western blot analysis, a strongly reactive 55- to 60-kDa
      antigen was recognized by BAL IgA and by serum IgG. In summary, mucosal
      immunization elicited specific cellular and humoral immune responses and
      protected against Pc lung infection after immunosuppression.

PMID- 9916095
TI  - Functional and immunogenic characterization of two cloned regions of
      Streptococcus mutans glucosyltransferase I.
AB  - Glucosyltransferase (GTF) enzymes of mutans streptococci are considered virulence
      factors due to their ability to synthesize adhesive glucans, which facilitate
      cell-to-cell adherence and accumulation. In this study we report the cloning,
      expression, and characterization of the catalytic (CAT) and glucan-binding (GLU)
      domains of S. mutans GTF-I encoded by gtfB. The CAT and GLU polypeptides
      represent amino acid residues 253 to 628 and 1183 to 1473, respectively, of S.
      mutans GTF-I. Antibodies to recombinant CAT and GLU were generated in rabbits and
      purified by affinity chromatography. Purified anti-CAT antibodies significantly
      inhibited water-insoluble glucan synthesis by S. mutans and S. sobrinus GTFs (P <
      0.0001 and P < 0.05, respectively). The purified anti-GLU antibodies
      significantly inhibited both water-insoluble and water-soluble glucan synthesis
      by S. mutans GTFs (P < 0.0001 and P < 0.05, respectively). These results
      demonstrate that anti-CAT and anti-GLU antibodies are capable of inhibiting a
      variety of GTF activities. Since antibodies to S. mutans in saliva are implicated
      in protection against disease, we next assessed the ability of CAT and GLU
      polypeptides to induce mucosal antibody responses in mice. Intranasal (i.n.)
      immunization of mice with CAT showed significantly (P < 0.005) elevated levels of
      specific immunoglobulin G (IgG) antibody activity in serum and specific IgA
      antibody activity in serum, saliva, vaginal washes, and fecal samples. GLU
      immunized animals showed significantly (P < 0.005) elevated levels of specific
      IgA antibody activity in serum and vaginal secretions. Taken together, these
      results demonstrate that the recombinant CAT and GLU polypeptides are effective
      in inducing both mucosal and systemic immune responses. The ability of these
      polypeptides to induce a mucosal IgA immune response in mice after i.n.
      immunization supports their use as subunit vaccine candidates in the development
      of an anticaries vaccine.

PMID- 9916096
TI  - Cytotoxic action of Serratia marcescens hemolysin on human epithelial cells.
AB  - Incubation of human epithelial cells with nanomolar concentrations of
      chromatographically purified Serratia marcescens hemolysin (ShlA) caused
      irreversible vacuolation and subsequent lysis of the cells. Vacuolation differed
      from vacuole formation by Helicobacter pylori VacA. Sublytic doses of ShlA led to
      a reversible depletion of intracellular ATP. Restoration to the initial ATP level
      was presumably due to the repair of the toxin damage and was inhibited by
      cycloheximide. Pores formed in epithelial cells and fibroblasts without
      disruption of the plasma membrane, and the pores appeared to be considerably
      smaller than those observed in artificial lipid membranes and in erythrocytes and
      did not allow the influx of propidium iodide or trypan blue. All cytotoxic
      effects induced by isolated recombinant ShlA were also obtained with
      exponentially growing S. marcescens cells. The previously suggested role of the
      hemolysin in the pathogenicity of S. marcescens is supported by these data.

PMID- 9916097
TI  - Effectiveness of a vaccine composed of heat-killed Candida albicans and a novel
      mucosal adjuvant, LT(R192G), against systemic candidiasis.
AB  - The incidence of fungal infections caused by the opportunistic yeast Candida
      albicans has increased significantly in recent years. The ability to vaccinate
      selected patients against the organism would be advantageous. In this paper we
      describe a potential anti-C. albicans vaccine consisting of heat-killed C.
      albicans (HK-CA) in combination with the novel mucosal adjuvant LT(R192G), a
      genetically detoxified form of the heat-labile toxin of enterotoxigenic
      Escherichia coli. Groups of male CBA/J mice were immunized intranasally on three
      occasions at weekly intervals with 2 x 10(7) HK-CA per dose, alone or in
      conjunction with 10 micrograms of LT(R192G) per dose. Two weeks following the
      last application of antigen, some animals were challenged intravenously (i.v.)
      with 10(4), 10(5), or 10(6) viable C. albicans to assess protection as measured
      by survival and/or culture. Some groups of animals were footpad tested with C.
      albicans mannan to assess delayed-type hypersensitivity (DTH), and all the
      animals were bled for antibody assays. In two independent studies, all the
      animals immunized with HK-CA plus LT(R192G) were able to eradicate 10(4) C.
      albicans completely, as determined by kidney culture 4 weeks after challenge.
      Animals immunized with HK-CA only had reduced levels of C. albicans compared to
      the adjuvant or saline-only control. Greatly enhanced survival was observed when
      mice immunized with HK-CA plus LT(R192G) were challenged with 10(5) live C.
      albicans as well. Animals immunized with HK-CA plus LT(R192G) developed a
      significant DH response, while those given HK-CA alone developed only marginal DH
      responses. High immunoglobulin G (IgG) levels to cytoplasmic antigens developed
      in mice immunized with HK-CA plus LT(R192G), but they were found only after i.v.
      challenge. Addition of adjuvant shifted the antibody isotype production in i.v.
      challenged animals to a response dominated by IgG2a. Clearly, intranasal
      immunization with killed C. albicans in conjunction with LT(R192G) afforded
      significant levels of protection. This novel approach offers new possibilities
      for the development of an effective vaccine against candidiasis for use in
      humans.

PMID- 9916098
TI  - Roles of PilC and PilE proteins in pilus-mediated adherence of Neisseria
      gonorrhoeae and Neisseria meningitidis to human erythrocytes and endothelial and
      epithelial cells.
AB  - Unlike other type 4 pili, the neisserial pili consist of at least two distinct
      proteins, the highly variable major subunit PilE forming the pilus fiber and the
      tip-associated adhesin PilC. PilC protein purified either from gonococci or from
      Escherichia coli interacted with different human epithelial cell lines, primary
      epithelial and endothelial cells. The binding of PilC protein efficiently
      prevented the attachment of piliated Neisseria gonorrhoeae and Neisseria
      meningitidis to these cell types. Fluorescent beads coated with pili prepared
      from piliated wild-type N. gonorrhoeae also adhered to these cells, in contrast
      to beads coated with pili prepared from a piliated PilC-deficient mutant. In the
      latter case, the binding of fluorescent beads was restored after pretreatment of
      the pilus-loaded beads with purified PilC. Piliated wild-type N. gonorrhoeae, the
      piliated PilC-deficient mutant, and N. gonorrhoeae pili assembled in Pseudomonas
      aeruginosa agglutinated human erythrocytes, while nonpiliated gonococci did not.
      Consistently, purified PilC did not agglutinate or bind to human erythrocytes,
      suggesting that N. gonorrhoeae PilE is responsible for pilus-mediated
      hemagglutination.

PMID- 9916099
TI  - A role for host phosphoinositide 3-kinase and cytoskeletal remodeling during
      Cryptosporidium parvum infection.
AB  - Cryptosporidium parvum preferentially infects epithelial cells lining the
      intestinal mucosa of mammalian hosts. Parasite development and propagation occurs
      within a unique intracellular but extracytoplasmic parasitophorous vacuole at the
      apical surface of infected cells. Parasite-induced host cell signaling events and
      subsequent cytoskeletal remodeling were investigated by using cultured bovine
      fallopian tube epithelial (BFTE) cells inoculated with C. parvum sporozoites.
      Indirect-immunofluorescence microscopy detected host tyrosine phosphorylation
      within 30 s of inoculation. At >30 min postinoculation, actin aggregates were
      detected at the site of parasite attachment by fluorescein isothiocyanate
      conjugated phalloidin staining as well as by indirect immunolabeling with
      monoclonal anti-actin. The actin-binding protein villin was also detected in
      focal aggregates at the site of attachment. Host cytoskeletal rearrangement
      persisted for the duration of the parasitophorous vacuole and contributed to the
      formation of long, branched microvilli clustered around the cryptosporidial
      vacuole. The phosphoinositide 3-kinase inhibitor wortmannin significantly
      inhibited (P < 0.05) C. parvum infection when BFTE cells were pretreated for 60
      min at 37 degreesC prior to inoculation. Similarly, treatment of BFTE cells with
      the protein kinase inhibitors genistein and staurosporine and the cytoskeletally
      acting compounds 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazapine,
      cytochalasin D, and 2,3-butanedione monoxime significantly inhibited (P < 0.05)
      in vitro infection at 24 h postinoculation. These findings demonstrate a
      prominent role for phosphoinositide 3-kinase activity during the early C. parvum
      infection process and suggest that manipulation of host signaling pathways
      results in actin rearrangement at the site of sporozoite attachment.

PMID- 9916100
TI  - Expression and distribution of leptospiral outer membrane components during renal
      infection of hamsters.
AB  - The outer membrane of pathogenic Leptospira species grown in culture media
      contains lipopolysaccharide (LPS), a porin (OmpL1), and several lipoproteins,
      including LipL36 and LipL41. The purpose of this study was to characterize the
      expression and distribution of these outer membrane antigens during renal
      infection. Hamsters were challenged with host-derived Leptospira kirschneri to
      generate sera which contained antibodies to antigens expressed in vivo.
      Immunoblotting performed with sera from animals challenged with these host
      derived organisms demonstrated reactivity with OmpL1, LipL41, and several other
      proteins but not with LipL36. Although LipL36 is a prominent outer membrane
      antigen of cultivated L. kirschneri, its expression also could not be detected in
      infected hamster kidney tissue by immunohistochemistry, indicating that
      expression of this protein is down-regulated in vivo. In contrast, LPS, OmpL1,
      and LipL41 were demonstrated on organisms colonizing the lumen of proximal
      convoluted renal tubules at both 10 and 28 days postinfection. Tubular epithelial
      cells around the luminal colonies had fine granular cytoplasmic LPS. When the
      cellular inflammatory response was present in the renal interstitium at 28 days
      postinfection, LPS and OmpL1 were also detectable within interstitial phagocytes.
      These data establish that outer membrane components expressed during infection
      have roles in the induction and persistence of leptospiral interstitial
      nephritis.

PMID- 9916101
TI  - Apoptosis in macrophages and alveolar epithelial cells during early stages of
      infection by Legionella pneumophila and its role in cytopathogenicity.
AB  - The hallmark of Legionnaires' disease is intracellular replication of Legionella
      pneumophila within cells in the alveolar spaces. Cytopathogenicity of this
      bacterium to the host cell has been well demonstrated, but the mechanisms of host
      cell death due to infection by L. pneumophila are not well understood. In this
      study, induction of apoptosis in macrophages and alveolar epithelial cells by L.
      pneumophila during early stages of infection was confirmed by using multiple
      criteria, including DNA fragmentation by agarose gel electrophoresis, terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling, surface exposure of
      phosphatidylserine, and cellular morphology by transmission electron microscopy.
      Induction of nuclear apoptosis in L. pneumophila-infected macrophages is mediated
      by activation of the caspase cascade death machinery. We provide genetic and
      biochemical evidence that L. pneumophila-induced apoptosis in macrophages and
      alveolar epithelial cells does not require intracellular bacterial replication or
      new protein synthesis. In addition, extracellular L. pneumophila is capable of
      inducing apoptosis. Furthermore, induction of apoptosis by L. pneumophila
      correlates with cytopathogenicity. We conclude that L. pneumophila-induced
      apoptosis in macrophages and alveolar epithelial cells plays an important role in
      cytopathogenicity to the host cell during early stages of infection.

PMID- 9916102
TI  - Lmb, a protein with similarities to the LraI adhesin family, mediates attachment
      of Streptococcus agalactiae to human laminin.
AB  - Streptococcus agalactiae is a leading cause of neonatal sepsis and meningitis.
      Adherence to extracellular matrix proteins is considered an important factor in
      the pathogenesis of infection, but the genetic determinants of this process
      remain largely unknown. We identified and sequenced a gene which codes for a
      putative lipoprotein that exhibits significant homology to the streptococcal LraI
      protein family. Mutants of this locus were demonstrated to have substantially
      reduced adherence to immobilized human laminin. The nucleotide sequence of the
      gene was subsequently designated lmb (laminin binding) and shown to be present in
      all of the common serotypes of S. agalactiae. To determine the role of Lmb in the
      adhesion of S. agalactiae wild-type strains to laminin, a recombinant Lmb protein
      harboring six consecutive histidine residues at the C terminus was cloned,
      expressed, and purified from Escherichia coli. Preincubation of immobilized
      laminin with recombinant Lmb significantly reduced adherence of the wild-type
      strain O90R to laminin. These results indicate that Lmb mediates the attachment
      of S. agalactiae to human laminin, which may be essential for the bacterial
      colonization of damaged epithelium and translocation of bacteria into the
      bloodstream.

PMID- 9916103
TI  - Urokinase-type plasminogen activator in inflammatory cell recruitment and host
      defense against Pneumocystis carinii in mice.
AB  - Effective host defense against Pneumocystis carinii depends upon the integrated
      actions of inflammatory cells and mediators in the lungs. Using immunocompetent
      and immunosuppressed mice, our laboratory has defined inflammatory changes in the
      lungs in response to P. carinii. However, the essential molecules and mechanisms
      required for cellular recruitment and for host defense against P. carinii are
      undefined. We hypothesized that urokinase-type plasminogen activator (uPA), a
      protease intimately involved in inflammatory cell migration and activation, is
      required for clearance of P. carinii. To test this hypothesis in vivo, we
      compared the intensity of P. carinii infection and inflammation in the lungs of
      mice lacking the uPA gene (uPA knockout mice) and in the lungs of wild-type mice.
      After intratracheal inoculation with P. carinii organisms, uPA knockout mice
      developed uniformly heavy P. carinii pneumonia while wild-type mice cleared the
      P. carinii inoculum. Bronchoalveolar lavage fluid from uPA knockout mice
      contained significantly smaller numbers of cells than did lavage fluid from wild
      type mice. We conclude that deletion of the uPA gene prevents the clearance of P.
      carinii and reduces inflammatory cell recruitment. Therefore, uPA is an important
      participant in the network of inflammatory events required for the clearance of
      P. carinii, confirming an important role for this molecule in pulmonary host
      defense against opportunistic pathogens.

PMID- 9916104
TI  - Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages.
AB  - Recently, we demonstrated that human monocyte-derived macrophages (MDM) treated
      with chloroquine or ammonium chloride had markedly increased antifungal activity
      against the AIDS-related pathogen Cryptococcus neoformans. Both of these agents
      raise the lysosomal pH, which suggested that the increased antifungal activity
      was a function of alkalinizing the phagolysosome. Moreover, there was an inverse
      correlation between growth of C. neoformans in cell-free media and pH. These data
      suggested that C. neoformans was well adapted to survive within acidic
      compartments. To test this hypothesis, we performed studies to determine the pH
      of human MDM and neutrophil phagosomes containing C. neoformans. Fungi were
      labeled with the isothiocyanate derivatives of two pH-sensitive probes:
      fluorescein and 2',7'-difluorofluorescein (Oregon Green). These probes have pKas
      of 6.4 and 4.7, respectively, allowing sensitive pH detection over a broad range.
      The phagosomal pH averaged approximately 5 after ingestion of either live or heat
      killed fungi and remained relatively constant over time, which suggested that C.
      neoformans does not actively regulate the pH of its phagosome. The addition of 10
      and 100 microM chloroquine resulted in increases in the phagosomal pH from a
      baseline of 5.1 up to 6.5 and 7.3, respectively. Finally, by immunofluorescence,
      colocalization of C. neoformans and the MDM lysosomal membrane protein LAMP-1 was
      demonstrated, establishing that fusion of C. neoformans-laden phagosomes with
      lysosomal compartments takes place. Thus, unlike many other intracellular
      pathogens, C. neoformans does not avoid fusion with macrophage lysosomal
      compartments but rather resides and survives in an acidic phagolysosome.

PMID- 9916105
TI  - In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression
      induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella
      infection, and inhibits macrophage and polymorphonuclear leukocyte influx into
      the spleen.
AB  - Our laboratory has previously shown that after immunization with a strain of
      Salmonella typhimurium, SL3235, made avirulent by a blockage in the pathway of
      aromatic synthesis, murine splenocytes were profoundly suppressed in their
      capacity to mount an in vitro antibody plaque-forming cell (PFC) response to
      sheep erythrocytes. Evidence indicated that suppression was mediated by nitric
      oxide (NO), since the in vitro addition of NG-monomethyl-L-arginine blocked
      suppression. The present studies examined the effect of blocking NO production on
      Salmonella-induced immunosuppression by in vivo administration of aminoguanidine
      hemisulfate (AG). AG was administered to C3HeB/FeJ mice in their drinking water
      (2.5% solution) for 7 days prior to intraperitoneal inoculation with SL3235. AG
      treatment inhibited the increase in nitrate and nitrite levels in plasma and
      nitrite levels in the spleen seen in immunized mice. Importantly, AG treatment
      completely blocked suppression of the splenic PFC response and markedly
      attenuated the suppression of the response to concanavalin A in immunized mice,
      providing further evidence that Salmonella-induced immunosuppression is mediated
      by NO. AG treatment also alleviated the majority of the splenomegaly associated
      with SL3235 inoculation, which correlated with a blockage of influx of
      neutrophils and macrophages into spleens, as assessed by flow cytometry. AG
      treatment unexpectedly resulted in 90% mortality in mice injected with the highly
      attenuated vaccine strain of Salmonella, SL3235. Increased mortality in AG
      treated mice correlated with inability to clear organisms from the spleen by day
      15 postinoculation and with persistent bacteremia, compared with control mice.
      Collectively, these in vivo results underscore the dual biological consequences
      of NO production following Salmonella infection, with NO being necessary for host
      defense, but also having the potentially adverse effect of immunosuppression. A
      unifying hypothesis to explain how these seemingly paradoxical effects could both
      result from NO production is presented.

PMID- 9916106
TI  - Characterization of a WaaF (RfaF) homolog expressed by Haemophilus ducreyi.
AB  - Haemophilus ducreyi lipooligosaccharide (LOS) is capable of inducing an
      inflammatory response in skin (A. A. Campagnari, L. M. Wild, G. Griffiths, R. J.
      Karalus, M. A. Wirth, and S. M. Spinola, Infect. Immun. 59:2601-2608, 1991) and
      likely contributes to the virulence of this sexually transmitted pathogen (B. A.
      Bauer, M. K. Stevens, and E. J. Hansen, Infect. Immun. 68:4290-4298, 1998). An
      open reading frame in H. ducreyi 35000 was found to encode a predicted protein
      that was 59% identical to the protein product of the rfaF (waaF) gene of
      Salmonella typhimurium. The H. ducreyi waaF gene was able to complement an S.
      typhimurium rfaF (waaF) mutant, a result which confirmed the identity of this
      gene. In contrast to the rfaF (waaF) gene of enteric bacteria, the H. ducreyi
      waaF gene was not located adjacent to other genes involved in lipopolysaccharide
      expression. Inactivation of the H. ducreyi waaF gene by insertion mutagenesis
      resulted in expression of a LOS that migrated much faster than wild-type LOS in
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The LOS of this mutant
      also did not bind a monoclonal antibody directed against a cell surface-exposed
      epitope of wild-type H. ducreyi LOS. Testing of the wild-type H. ducreyi strain
      and its isogenic waaF mutant in the temperature-dependent rabbit model for dermal
      lesion production by H. ducreyi revealed that this waaF mutant was less virulent
      than the wild-type parent strain. Complementation of the H. ducreyi waaF mutant
      with the wild-type H. ducreyi waaF gene resulted in expression of both wild-type
      LOS and wild-type virulence by this mutant.

PMID- 9916107
TI  - A melanin pigment purified from an epidemic strain of Burkholderia cepacia
      attenuates monocyte respiratory burst activity by scavenging superoxide anion.
AB  - The acquisition of Burkholderia cepacia in some cystic fibrosis patients is
      associated with symptoms of acute pulmonary inflammation that may be life
      threatening. The ability of lipopolysaccharide (LPS) from B. cepacia to prime a
      monocyte cell line for enhanced superoxide anion generation was investigated and
      compared with the priming activities of LPSs from Pseudomonas aeruginosa,
      Stenotrophomonas maltophilia, and Escherichia coli. The human monocyte cell line
      MonoMac-6 (MM6) was primed overnight with different LPSs (100 ng/ml), and the
      respiratory burst was triggered by exposure to opsonized zymosan (125
      micrograms/ml). Superoxide generation was detected by enhanced chemiluminescence
      with Lucigenin. B. cepacia LPS was found to prime MM6 cells to produce more
      superoxide anion than P. aeruginosa or S. maltophilia LPS, and this priming
      response was CD14 dependent. In addition, the inhibition of respiratory burst
      responses in monocytes by a bacterial melanin-like pigment purified from an
      epidemic B. cepacia strain was investigated. The melanin-like pigment was
      isolated from tyrosine-enriched media on which B. cepacia had been grown and was
      purified by gel filtration, anion ion-exchange chromatography, and ethanol
      precipitation. The scavenging potential of the melanin-like pigment for
      superoxide anion radical (*O2-) generated during the respiratory burst was
      confirmed with superoxide produced from a cell-free system with xanthine-xanthine
      oxidase and detected by electron paramagnetic resonance spectroscopy with the
      spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-n-oxide. The addition of
      melanin during the LPS priming stage had no effect on the subsequent triggering
      of the respiratory burst, but melanin inhibited *O2- detection when added at the
      triggering stage of the respiratory burst. We conclude that melanin-producing B.
      cepacia may derive protection from the free-radical-scavenging properties of this
      pigment.

PMID- 9916108
TI  - Regulation of ExoS production and secretion by Pseudomonas aeruginosa in response
      to tissue culture conditions.
AB  - This study was initiated to characterize the regulation and secretion of ExoS by
      Pseudomonas aeruginosa during contact with eukaryotic cells. The production of
      ExoS was monitored by a sensitive ADP-ribosyltransferase activity assay, and
      specific activities were calculated for supernatant and cell-associated
      fractions. Time course analysis indicated that ExoS was produced after a lag
      period, suggesting that induction of the regulon is necessary for the expression
      of detectable amounts of enzyme activity. Under tissue culture growth conditions,
      ExoS was induced when P. aeruginosa was in contact with Chinese hamster ovary
      (CHO) cells or after growth in tissue culture medium with serum. The serum
      induction of ExoS appeared to result in generalized type III secretion, while
      induction by contact with CHO cells appeared to result in polarized type III
      secretion. Mutants in the type III secretory system that express a null phenotype
      for ExoS production in bacteriological medium produced but did not secrete the
      enzyme when P. aeruginosa was grown under inducing conditions in tissue culture
      medium. These results suggest that both induction and secretion of ExoS may
      differ when the bacteria are exposed to different growth environments. The
      putative type III translocation proteins and secretion apparatus of P. aeruginosa
      were required for translocation of bacterial factors that mediate changes in CHO
      cell morphology during infection.

PMID- 9916111
TI  - The cell wall and membrane of Cryptococcus neoformans possess a mitogen for human
      T lymphocytes.
AB  - The mechanism of human T-lymphocyte activation by the pathogenic yeast
      Cryptococcus neoformans has not been established. Previous investigations have
      suggested that C. neoformans contains a mitogen for T lymphocytes, while other
      investigators have attributed lymphocyte proliferation in vitro to a recall
      antigen. Because of the potential importance of the mechanism of T-cell
      activation for our understanding of the immune response to C. neoformans, the
      present studies were performed to determine whether C. neoformans contains a
      mitogen for T lymphocytes. C. neoformans stimulates fetal blood lymphocytes to
      proliferate and stimulates proliferation of CD45RA+ cells from adults, indicating
      that it stimulates naive T cells. The T-cell response to C. neoformans was
      dependent upon the presence of accessory cells. However, allogeneic cells were
      sufficient for accessory cell function, indicating that the response was not
      major histocompatibility complex restricted. The percentage of T cells in the
      cell cycle was higher than that with the recall antigen tetanus toxoid but lower
      than that with the mitogenic lectin phytohemagglutinin A or the superantigen
      Staphylococcus enterotoxin B. Precursor frequency analysis established that 1 in
      7,750 +/- 2, 270 T cells proliferated in response to the cryptococcal cell wall
      and membrane. Compared to the case for most mitogens or superantigens, the
      proliferative response is late and the number of T cells that enter the cell
      cycle and the precursor frequency are low, indicating that the mitogenic effect
      is modest. However, the mitogenic effect of C. neoformans should be considered
      when interpreting the immune response to C. neoformans, since even weak mitogens
      can have profound effects on host defense.

PMID- 9916109
TI  - Antigen-specific T-cell responses in humans after intranasal immunization with a
      meningococcal serogroup B outer membrane vesicle vaccine.
AB  - We have studied the ability of the Norwegian group B meningococcal outer membrane
      vesicle (OMV) vaccine, when administered intranasally without adjuvant, to induce
      T-cell responses in humans. A group of 12 vaccinees was immunized with four doses
      of OMVs (250 micrograms of protein/dose) at weekly intervals, and a single
      booster dose was given 5 months later. In vitro T-cell proliferation in response
      to the OMV vaccine, purified PorA (class 1) protein, PorB (class 3) protein, and
      one unrelated control antigen (Mycobacterium bovis BCG) was measured by
      [3H]thymidine incorporation into peripheral blood mononuclear cells obtained from
      the vaccinees before and after the immunizations. The nasal OMV immunizations
      induced antigen-specific T-cell responses in the majority of the vaccinees when
      tested against OMVs (7 of 12) and the PorA antigen (11 of 12). None of the
      vaccinees showed a vaccine-induced T-cell response to the PorB antigen after the
      initial four doses. Although some individuals responded to all the vaccine
      antigens after the booster dose, this response was not significant when the
      vaccinees were analyzed as a group. We have also demonstrated that the PorA
      antigen-specific T-cell responses correlated with anti-OMV immunoglobulin A (IgA)
      levels in nasal secretions, with anti-OMV IgG levels in serum, and with serum
      bactericidal activity. In conclusion, we have shown that it is possible to induce
      antigen-specific T-cell responses in humans by intranasal administration of a
      meningococcal OMV vaccine without adjuvant.

PMID- 9916110
TI  - Fas-FasL interaction involved in pathogenesis of ocular toxoplasmosis in mice.
AB  - Ocular toxoplasmosis is a potentially blinding intraocular inflammation. The
      intent of this study was to investigate the role of Fas-FasL interaction in a
      murine model of acquired ocular toxoplasmosis induced by intracameral inoculation
      of Toxoplasma gondii. Intraocular inflammation, Fas and FasL expression on
      lymphocytes and on ocular tissues, the occurrence of apoptosis, and the frequency
      of CD8(+) and CD4(+) T cells in the infected eyes were analyzed in C57BL/6 (B6)
      mice. Susceptibility to parasite-induced intraocular inflammation was observed in
      Fas-deficient (B6-lpr) and FasL-deficient (B6-gld) mice. Inoculation of 5,000 T.
      gondii tachyzoites induced significant intraocular inflammation associated with
      increase of Fas and FasL expression in the inoculated eyes of wild-type B6 mice.
      Flow cytometry demonstrated a significant increase of Fas and FasL expression on
      the splenocytes from naive mice incubated in vitro with the parasite and on the
      splenocytes harvested from the infected mice at day 8 after parasite inoculation.
      Apoptosis of inflammatory cells and cells in ocular tissues was seen, and a
      greater frequency of CD8(+) than CD4(+) T cells was observed in the infected
      eyes. The intensity of intraocular inflammation was greater in B6-lpr and B6-gld
      mice than in wild-type B6 mice (P < 0.05). The results suggest that Fas-FasL
      interaction associated with apoptosis is involved in the pathogenesis of acquired
      ocular toxoplasmosis in mice.

PMID- 9916112
TI  - Cloning of the gene encoding the Actinobacillus actinomycetemcomitans serotype b
      OmpA-like outer membrane protein.
AB  - The gene encoding an outer membrane protein A (OmpA)-like, heat-modifiable Omp of
      Actinobacillus actinomycetemcomitans ATCC 43718 (strain Y4, serotype b) was
      cloned by a PCR cloning procedure. DNA sequence analysis revealed that the gene
      encodes a protein of 346 amino acid residues with a molecular mass of 36.9 kDa.
      The protein expressed by the cloned gene reacted with a monoclonal antibody to
      the previously described 29-kDa Omp (Omp29) of strain Y4. This monoclonal
      antibody reacted specifically with Omp29 of A. actinomycetemcomitans (serotype
      b), but not with any Omp of Escherichia coli, including OmpA. This protein
      exhibited characteristic heat modifiability on sodium dodecyl sulfate
      polyacrylamide gels, showing an apparent molecular mass of 29 kDa when unheated
      and a mass of 34 kDa when heated. The N-terminal amino acid sequence of the
      protein expressed in E. coli perfectly matched those deduced from the purified
      Omp29 of strain Y4. The deduced amino acid sequence of the gene coding for Omp29
      from serotype b matched completely (except for valine at position 321) that of a
      recently reported omp34 gene described for A. actinomycetemcomitans serotype c
      (NCTC 9710). Because of the conserved nature of the gene within these serotypes,
      we designated the gene described herein from serotype b as omp34.

PMID- 9916114
TI  - Role of lipopolysaccharide sialylation in serum resistance of serogroup B and C
      meningococcal disease isolates.
AB  - alpha-2,3-Sialyltransferase mutants of three genetically and phenotypically
      diverse Neisseria meningitidis strains were compared with regard to resistance to
      human serum and systemic spread in the infant rat. Lipopolysaccharide sialylation
      was found to be of minor importance for the resistance of serogroup B and C
      meningococcal disease isolates to complement attack.

PMID- 9916113
TI  - Human intestinal M cells display the sialyl Lewis A antigen.
AB  - The biochemical features that distinguish human M cells from other intestinal
      epithelial cell types are important for understanding microbial pathogenesis and
      for targeting vaccines to the mucosal immune system. We applied a large panel of
      carbohydrate-specific monoclonal antibodies and lectins to Peyer's patch and
      cecum biopsy specimens from three normal individuals and a patient with
      inflammatory bowel disease. The results show that human M-cell glycosylation
      patterns are distinct from those of other species examined and that human M cells
      preferentially display the sialyl Lewis A antigen. This carbohydrate epitope is
      also present in a small subpopulation of enterocytes in the follicle-associated
      epithelium and in goblet cell mucins.

PMID- 9916115
TI  - Isolation and characterization of rugose form of Vibrio cholerae O139 strain
      MO10.
AB  - An extracellular exopolysaccharide (slime) is produced by Vibrio cholerae O139
      MO10 in response to nutrient starvation. The presence of this slime layer on the
      cell surface and its subsequent release have been shown to be associated with
      biofilm formation and the change from a normal smooth colony morphology to a
      rugose one. An immunoelectron microscopic examination demonstrated that there is
      an epitope common to the exopolysaccharide antigen of V. cholerae O1 and that of
      O139 MO10.

PMID- 9916116
TI  - Functional analysis of the carboxy-terminal domain of Bacillus anthracis
      protective antigen.
AB  - Protective antigen (PA) is the common receptor-binding component of the two
      anthrax toxins. We investigated the involvement of the PA carboxy-terminal domain
      in the interaction of the protein with cells. A deletion resulting in removal of
      the entire carboxy-terminal domain of PA (PA608) or part of an exposed loop of 19
      amino acids (703 to 722) present within this domain was introduced into the pag
      gene. PA608 did not induce the lethal-factor (LF)-mediated cytotoxic effect on
      macrophages because it did not bind to the receptor. In contrast, PA711- and
      PA705-harboring lethal toxins (9- and 16-amino-acid deletions in the loop,
      starting after positions 711 and 705, respectively) were 10 times less cytotoxic
      than wild-type PA. After cleavage by trypsin, the mutant PA proteins formed
      heptamers and bound LF. The capacity of PA711 and PA705 to interact with cells
      was 1/10 that of wild-type PA. In conclusion, truncation of the carboxy-terminal
      domain or deletions in the exposed loop resulted in PA that was less cytotoxic or
      nontoxic because the mutated proteins did not efficiently bind to the receptor.

PMID- 9916118
TI  - Pseudomonas aeruginosa keratitis in knockout mice deficient in intercellular
      adhesion molecule 1.
AB  - In this study, the role of intercellular adhesion molecule 1 (ICAM-1) in the
      pathogenesis of Pseudomonas aeruginosa keratitis was examined by using inbred
      ICAM-1-deficient knockout mice. These mice had significantly less (P </= 0.02)
      ocular disease than wild-type mice, suggesting that ICAM-1 contributes to a more
      severe disease response following P. aeruginosa infection.

PMID- 9916117
TI  - Production of enterotoxin by Yersinia bercovieri, a recently identified Yersinia
      enterocolitica-like species.
AB  - Yersinia bercovieri, a recently identified Y. enterocolitica-like species,
      produces a heat-stable enterotoxin (designated YbST) which has biologic activity
      in infant mice and increases short circuit current in Ussing chambers. Although
      YbST has some properties in common with the heat-stable enterotoxins of Y.
      enterocolitica (YST I and YST II), it appears to be a novel toxin because (i) it
      was not neutralized by anti-YST I antiserum, (ii) YbST-neutralizing antiserum did
      not neutralize YST I, and (iii) Y. bercovieri strains did not hybridize with
      genetic probes for yst I, yst II, and other known enterotoxins.

PMID- 9916119
TI  - rfb mutations in Vibrio cholerae do not affect surface production of toxin
      coregulated pili but still inhibit intestinal colonization.
AB  - The toxin-coregulated pilus (TCP) of Vibrio cholerae is essential for
      colonization. It was recently reported that rfb mutations in V. cholerae 569B
      cause the translocation arrest of the structural subunit of TCP, raising the
      possibility that the colonization defects of lipopolysaccharide mutants are due
      to effects on TCP biogenesis. However, an rfbB gene disruption in either V.
      cholerae O395 or 569B has no apparent effect on surface TCP production as
      assessed by immunoelectron microscopy and CTX phage transduction, and an
      rfbD::Tn5lac mutant of O395 also shows no defect in TCP expression. We conclude
      that the colonization defect associated with rfb mutations is unrelated to
      defects in TCP assembly.

PMID- 9916120
TI  - Comparative virulence of Streptococcus pneumoniae strains with insertion
      duplication, point, and deletion mutations in the pneumolysin gene.
AB  - Pneumolysin is a 471-amino-acid toxin produced by Streptococcus pneumoniae which
      has both cytolytic and complement activation properties. We have constructed a
      derivative of the type 2 S. pneumoniae strain D39 in which the portion of the
      pneumolysin gene encoding amino acids 55 to 437 has been deleted in-frame. The
      virulence of this strain (DeltaPly) was compared with those of wild-type D39, a
      pneumolysin insertion-duplication mutant (PLN-A), and a derivative (PdT) carrying
      a toxin gene with three point mutations known to abolish both cytolytic activity
      and complement activation. PdT was intermediate in virulence between D39 and
      either PLN-A or DeltaPly in a mouse intraperitoneal challenge model. This
      provides unequivocal evidence that pneumolysin has an additional property that is
      not abolished by point mutations which reduce cytotoxicity and complement
      activation to virtually undetectable levels.

PMID- 9916121
TI  - Vaccination with live Escherichia coli expressing Brucella abortus Cu/Zn
      superoxide dismutase protects mice against virulent B. abortus.
AB  - Vaccination of mice with Escherichia coli expressing Brucella Cu/Zn superoxide
      dismutase (SOD) [E. coli(pBSSOD)] induced a significant level of protection
      against virulent Brucella abortus challenge, although this level was not as high
      as the one reached with B. abortus vaccine strain RB51. In addition, vaccination
      with E. coli(pBSSOD) induced antibodies to Cu/Zn SOD and a strong proliferative
      response of splenocytes when stimulated in vitro with a thioredoxin-Cu/Zn SOD
      fusion protein.

PMID- 9916122
TI  - Interleukin-5 transgenic mice show enhanced resistance to primary infections with
      Nippostrongylus brasiliensis but not primary infections with Toxocara canis.
AB  - In this study, interleukin-5 (IL-5) transgenic mice with lifelong eosinophilia
      were assessed for resistance to primary infections with two tissue-invading
      nematodes, Nippostrongylus brasiliensis and Toxocara canis. Relative to
      nontransgenic littermates, three lines of IL-5 transgenic mice with varying
      degrees of eosinophilia all displayed enhanced resistance to N. brasiliensis.
      Although the timing of final worm expulsion was similar in transgenic and
      nontransgenic hosts, intestinal worms in transgenic mice were fewer in number
      throughout infection, failed to increase in size over the course of the
      infection, and were much less fecund. In contrast, T. canis larvae were recovered
      in similar numbers from tissues of transgenic mice with "low" or "high"
      eosinophilia and from nontransgenic mice. These results and other data suggest
      that eosinophils can contribute to host resistance to some parasite species.
      Parasite transit time through the host may correlate with relative sensitivity to
      eosinophils.

PMID- 9916123
TI  - Polysaccharide binding potential of the human A2 or A18 kappa light chain
      homologues.
AB  - Antibodies having light (L) chains encoded by the kappaII-A2 variable region gene
      segment predominate in the human response to the Haemophilus influenzae type b
      polysaccharide (Hib PS). To determine whether the closely related homologue of
      the A2 gene, the kappaII-A18 gene, has the potential to contribute to the
      repertoire, we examined Hib PS binding to a series of recombinant Fab fragments
      having either A2 or A18 L chains isolated from a Hib PS-vaccinated adult. The
      ability to bind Hib PS resided exclusively with those Fab fragments having A2 and
      containing an insertional arginine at the variable-joining junction. Thus,
      despite the sequence similarity between A2 and A18, only A2 contributes to the
      canonical Hib PS paratope.

PMID- 9916124
TI  - All accessible epitopes in the Salmonella lipopolysaccharide core are associated
      with branch residues.
AB  - Antisera generated against each of the nine known chemotypes of Salmonella
      lipopolysaccharide (LPS) core were characterized in order to delineate cross
      reactive epitopes and define the bases for their accessibility. Strongly cross
      reactive epitopes were associated with three chemotypes: Ra and Rb4, which
      recognized alpha-GlcNAc-1-->2-alpha-Glc, and Rd1, which recognized L-alpha-D
      heptose-1-->7-L-alpha-D-heptose. Both these disaccharides and the more weakly
      cross-reactive alpha-Gal-1-->6-alpha-Glc terminal in Rb3 LPS represent branch
      points along the core oligosaccharide. Therefore, branch points in endotoxin core
      oligosaccharides may generally be cross-reactive.

PMID- 9916125
TI  - Essential functional role of the polysaccharide intercellular adhesin of
      Staphylococcus epidermidis in hemagglutination.
AB  - Hemagglutination of erythrocytes is a common property of Staphylococcus
      epidermidis strains, which is related to adherence and biofilm formation and may
      be essential for the pathogenesis of biomaterial-associated infections caused by
      S. epidermidis. In three independent biofilm-producing, hemagglutination-positive
      S. epidermidis isolates, interruption of the icaADBC operon essential for
      polysaccharide intercellular adhesin (PIA) synthesis by Tn917 insertions led to a
      hemagglutination-negative phenotype. An immunoglobulin G fraction of antiserum to
      PIA greatly reduced hemagglutination. Purified PIA led to a 64-fold decrease of
      hemagglutination titers of these strains; however, it did not mediate
      hemagglutination by itself. These observations define PIA as the hemagglutinin of
      S. epidermidis or at least as its major functional component.

PMID- 9916126
TI  - Blood vessel maturation: vascular development comes of age.

PMID- 9916127
TI  - Selective ablation of immature blood vessels in established human tumors follows
      vascular endothelial growth factor withdrawal.
AB  - Features that distinguish tumor vasculatures from normal blood vessels are sought
      to enable the destruction of preformed tumor vessels. We show that blood vessels
      in both a xenografted tumor and primary human tumors contain a sizable fraction
      of immature blood vessels that have not yet recruited periendothelial cells.
      These immature vessels are selectively obliterated as a consequence of vascular
      endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the
      selective vulnerability of immature vessels to VEGF loss was demonstrated by
      downregulating VEGF transgene expression using a tetracycline-regulated
      expression system. In human prostate cancer, the constitutive production of VEGF
      by the glandular epithelium was suppressed as a consequence of androgen-ablation
      therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in
      vessels devoid of periendothelial cells. These results suggest that the unique
      dependence on VEGF of blood vessels lacking periendothelial cells can be
      exploited to reduce an existing tumor vasculature.

PMID- 9916128
TI  - Compartmentalization of extracellular cGMP determines absorptive or secretory
      responses in the rat jejunum.
AB  - We examined potential mechanisms by which angiotensin subtype-2 (AT2) receptor
      stimulation induces net fluid absorption and serosal guanosine cyclic 3',5'
      monophosphate (cGMP) formation in the rat jejunum. L-arginine (L-ARG) given
      intravenously or interstitially enhanced net fluid absorption and cGMP formation,
      which were completely blocked by the nitric oxide (NO) synthase inhibitor, N
      nitro-L-arginine methylester (L-NAME), but not by the specific AT2 receptor
      antagonist, PD-123319 (PD). Dietary sodium restriction also increased jejunal
      interstitial fluid cGMP and fluid absorption. Both could be blocked by PD or L
      NAME, suggesting that the effects of sodium restriction occur via ANG II at the
      AT2 receptor. L-ARG-stimulated fluid absorption was blocked by the soluble
      guanylyl cyclase inhibitor 1-H-[1,2,4]oxadiazolo[4, 2-alpha]quinoxalin-1-one
      (ODQ). Cyclic GMP-specific phosphodiesterase in the interstitial space decreased
      extracellular cGMP content and prevented the absorptive effects of L-ARG.
      Angiotensin II (ANG II) caused an increase in net Na+ and Cl- ion absorption and
      22Na+ unidirectional efflux (absorption) from the jejunal loop. In contrast,
      intraluminal heat-stable enterotoxin of Escherichia coli (STa) increased loop
      cGMP and fluid secretion that were not blocked by either L-NAME or ODQ. These
      findings suggest that ANG II acts at the serosal side via AT2 receptors to
      stimulate cGMP production via soluble guanylyl cyclase activation and absorption
      through the generation of NO, but that mucosal STa activation of particulate
      guanylyl cyclase causes secretion independently of NO, thus demonstrating the
      opposite effects of cGMP in the mucosal and serosal compartments of the jejunum.

PMID- 9916129
TI  - Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway
      hyperreactivity but cause severe airway inflammation.
AB  - Allergic asthma, which is present in as many as 10% of individuals in
      industrialized nations, is characterized by chronic airway inflammation and
      hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4
      (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been
      proposed that immune deviation toward Th1 can protect against asthma and
      allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2,
      and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells
      to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines
      were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic
      mice and transferred into lymphocyte-deficient, OVA-treated severe combined
      immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant
      airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not
      attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID
      mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe
      airway inflammation. These results indicate that antigen-specific Th1 cells may
      not protect or prevent Th2-mediated allergic disease, but rather may cause acute
      lung pathology. These findings have significant implications with regard to
      current therapeutic goals in asthma and allergy and suggest that conversion of
      Th2-dominated allergic inflammatory responses into Th1-dominated responses may
      lead to further problems.

PMID- 9916131
TI  - TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and
      bone metastases development.
AB  - Breast cancer frequently metastasizes to the skeleton, and the associated bone
      destruction is mediated by the osteoclast. Growth factors, including transforming
      growth factor-beta (TGF-beta), released from bone matrix by the action of
      osteoclasts, may foster metastatic growth. Because TGF-beta inhibits growth of
      epithelial cells, and carcinoma cells are often defective in TGF-beta responses,
      any role of TGF-beta in metastasis is likely to be mediated by effects on the
      surrounding normal tissue. However, we present evidence that TGF-beta promotes
      breast cancer metastasis by acting directly on the tumor cells. Expression of a
      dominant-negative mutant (TbetaRIIDeltacyt) of the TGF-beta type II receptor
      rendered the human breast cancer cell line MDA-MB-231 unresponsive to TGF-beta.
      In a murine model of bone metastases, expression of TbetaRIIDeltacyt by MDA-MB
      231 resulted in less bone destruction, less tumor with fewer associated
      osteoclasts, and prolonged survival compared with controls. Reversal of the
      dominant-negative signaling blockade by expression of a constitutively active TGF
      beta type I receptor in the breast cancer cells increased tumor production of
      parathyroid hormone-related protein (PTHrP), enhanced osteolytic bone metastasis,
      and decreased survival. Transfection of MDA-MB-231 cells that expressed the
      dominant-negative TbetaRIIDeltacyt with the cDNA for PTHrP resulted in
      constitutive tumor PTHrP production and accelerated bone metastases. These data
      demonstrate an important role for TGF-beta in the development of breast cancer
      metastasis to bone, via the TGF-beta receptor-mediated signaling pathway in tumor
      cells, and suggest that the bone destruction is mediated by PTHrP.

PMID- 9916130
TI  - Glucose or diabetes activates p38 mitogen-activated protein kinase via different
      pathways.
AB  - Hyperglycemia can cause vascular dysfunctions by multiple factors including
      hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We
      have characterized the effect of hyperglycemia on p38 mitogen-activated protein
      (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and
      proinflammatory cytokines, leading to apoptosis, cell growth, and gene
      regulation. Glucose at 16.5 mM increased p38 kinase activity in a time-dependent
      manner compared with 5.5 mM in rat aortic smooth muscle cells (SMC). Mannitol
      activated p38 kinase only at or greater than 22 mM. High glucose levels and a PKC
      agonist activated p38 kinase, and a PKC inhibitor, GF109203X, prevented its
      activation. However, p38 kinase activation by mannitol or tumor necrosis factor
      alpha was not inhibited by GF109203X. Changes in PKC isoform distribution after
      exposure to 16.5 mM glucose in SMC suggested that both PKC-beta2 and PKC-delta
      isoforms were increased. Activities of p38 kinase in PKC-delta- but not PKC-beta1
      overexpressed SMC were increased compared with control cells. Activation of p38
      kinase was also observed and characterized in various vascular cells in culture
      and aorta from diabetic rats. Thus, moderate hyperglycemia can activate p38
      kinase by a PKC-delta isoform-dependent pathway, but glucose at extremely
      elevated levels can also activate p38 kinase by hyperosmolarity via a PKC
      independent pathway.

PMID- 9916133
TI  - Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes
      congenital afibrogenemia.
AB  - Congenital afibrinogenemia is a rare autosomal recessive disorder characterized
      by the complete absence of detectable fibrinogen. Uncontrolled bleeding after
      birth from the umbilical cord is common, and spontaneous intracerebral bleeding
      and splenic rupture can occur throughout life. Patients respond well to
      fibrinogen replacement therapy, either prophylactically or on demand. Because the
      half-life of infused fibrinogen is essentially normal, the genetic defect is
      assumed to be at the level of synthesis, but no responsible locus has been
      identified. Preliminary studies using Southern blotting suggested that no gross
      structural changes of the fibrinogen genes were present in patients. We report
      the identification of causative mutations in a nonconsanguineous Swiss family
      with congenital afibrinogenemia. The four affected male individuals (two brothers
      and their two first cousins) have homozygous deletions of approximately 11 kb of
      the fibrinogen alpha-chain gene (FGA). Haplotype data suggest that these
      deletions occurred separately, on three distinct ancestral chromosomes, implying
      that the FGA region of the fibrinogen locus is susceptible to deletion by a
      common mechanism. Furthermore, our results demonstrate that humans, like mice,
      may be born without the capacity to synthesize functional fibrinogen.

PMID- 9916132
TI  - Hypoglycemia and impaired hepatic glucose production in mice with a deletion of
      the C/EBPbeta gene.
AB  - The transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is
      enriched in liver and adipose tissue and controls the expression of a wide
      variety of genes coding for important metabolic pathways, including
      gluconeogenesis and lipid synthesis. To investigate the role of C/EBPbeta on
      glucose homeostasis, we studied mice with a targeted deletion of the gene for
      C/EBPbeta-/- mice. Adult C/EBPbeta-/- mice have hypoglycemia after an 18-hour
      fast, accompanied by lower hepatic glucose production (40% of that of wild-type
      mice), with no change in plasma insulin and a lower concentration of plasma free
      fatty acids (FFA). Glucagon infusion during a pancreatic clamp acutely stimulated
      hepatic glucose production by 38% in wild-type animals, with no change detected
      in C/EBPbeta-/- mice. Unexpectedly, both the basal and glucagon-stimulated
      hepatic cyclic adenosine monophosphate (cAMP) levels were lower in C/EBPbeta-/-
      mice, indicating an essential role for C/EBPbeta in controlling proximal signal
      transduction. Fasting hypoglycemia was associated with normal levels of
      phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene
      expression, however net liver glycogenolysis was impaired in C/EBPbeta-/- mice.
      FFA release from isolated adipose tissue in response to epinephrine was 68% lower
      in C/EBPbeta-/- mice than in control animals; however, N6,O2'-dibutyryladenosine
      (Bt2) cAMP stimulated a twofold increase in FFA release in C/EBPbeta-/- compared
      with no further increase in wild-type mice. Because a deletion in the gene for
      C/EBPbeta reduces blood glucose and circulating FFA, it could be an important
      therapeutic target for the treatment of non-insulin-dependent diabetes and
      possibly obesity, based on designing antagonists that decrease C/EBPbeta
      activity.

PMID- 9916134
TI  - High-density lipoprotein enhancement of anticoagulant activities of plasma
      protein S and activated protein C.
AB  - Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol
      levels are associated, respectively, with either increased risk or apparent
      protective effects for atherothrombosis. The ability of purified LDL and HDL to
      downregulate thrombin formation, a contributor to atherothrombotic processes, was
      assessed. Purified HDL, but not LDL, significantly enhanced inactivation of
      coagulation factor Va by activated protein C (APC) and protein S, and HDL
      stimulated protein S-dependent proteolytic inactivation of Va by APC, apparently
      due to cleavage at Arg306 in Va. In normal plasma, added HDL enhanced APC/protein
      S anticoagulant activity in modified prothrombin-time clotting assays. When the
      anticoagulant potency of HDL was compared with phospholipid (PL) vesicles of well
      defined composition using this assay, HDL appeared qualitatively different from
      PL vesicles because HDL showed only good anticoagulant activity, whereas PL
      vesicles were rather procoagulant. When 20 normal plasmas were tested using this
      clotting assay, apoA-I levels correlated with anticoagulant response to
      APC/protein S (r = 0.47, P = 0.035), but not with activated partial
      thromboplastin time-based APC resistance ratios. Because HDL enhances the
      anticoagulant protein C pathway in vitro, we speculate that HDL may help
      downregulate thrombin generation in vivo and that this anticoagulant action is
      one of HDL's beneficial activities.

PMID- 9916135
TI  - Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing
      placental defects and reduced survival.
AB  - beta3 integrins have been implicated in a wide variety of functions, including
      platelet aggregation and thrombosis (alphaIIbbeta3) and implantation,
      placentation, angiogenesis, bone remodeling, and tumor progression (alphavbeta3).
      The human bleeding disorder Glanzmann thrombasthenia (GT) can result from defects
      in the genes for either the alphaIIb or the beta3 subunit. In order to develop a
      mouse model of this disease and to further studies of hemostasis, thrombosis, and
      other suggested roles of beta3 integrins, we have generated a strain of beta3
      null mice. The mice are viable and fertile, and show all the cardinal features of
      GT (defects in platelet aggregation and clot retraction, prolonged bleeding
      times, and cutaneous and gastrointestinal bleeding). Implantation appears to be
      unaffected, but placental defects do occur and lead to fetal mortality. Postnatal
      hemorrhage leads to anemia and reduced survival. These mice will allow analyses
      of the other suggested functions of beta3 integrins and we report that postnatal
      neovascularization of the retina appears to be beta3-integrin-independent,
      contrary to expectations from inhibition experiments.

PMID- 9916137
TI  - Effects of free fatty acids on glucose transport and IRS-1-associated
      phosphatidylinositol 3-kinase activity.
AB  - To examine the mechanism by which free fatty acids (FFA) induce insulin
      resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and
      intracellular glucose concentrations were measured using carbon-13 and
      phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects
      before and after a hyperinsulinemic-euglycemic clamp following a five-hour
      infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated
      phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle
      biopsy samples obtained from seven additional subjects before and after an
      identical protocol. Rates of insulin stimulated whole-body glucose uptake.
      Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the
      lipid infusion compared with the glycerol infusion and were associated with a
      approximately 90% decrease in the increment in intramuscular glucose-6-phosphate
      concentration, implying diminished glucose transport or phosphorylation activity.
      To distinguish between these two possibilities, intracellular glucose
      concentration was measured and found to be significantly lower in the lipid
      infusion studies, implying that glucose transport is the rate-controlling step.
      Insulin stimulation, during the glycerol infusion, resulted in a fourfold
      increase in PI 3-kinase activity over basal that was abolished during the lipid
      infusion. Taken together, these data suggest that increased concentrations of
      plasma FFA induce insulin resistance in humans through inhibition of glucose
      transport activity; this may be a consequence of decreased IRS-1-associated PI 3
      kinase activity.

PMID- 9916136
TI  - Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D
      binding protein.
AB  - A line of mice deficient in vitamin D binding protein (DBP) was generated by
      targeted mutagenesis to establish a model for analysis of DBP's biological
      functions in vitamin D metabolism and action. On vitamin D-replete diets, DBP-/-
      mice had low levels of total serum vitamin D metabolites but were otherwise
      normal. When maintained on vitamin D-deficient diets for a brief period, the DBP
      /-, but not DBP+/+, mice developed secondary hyperparathyroidism and the
      accompanying bone changes associated with vitamin D deficiency. DBP markedly
      prolonged the serum half-life of 25(OH)D and less dramatically prolonged the half
      life of vitamin D by slowing its hepatic uptake and increasing the efficiency of
      its conversion to 25(OH)D in the liver. After an overload of vitamin D, DBP-/-
      mice were unexpectedly less susceptible to hypercalcemia and its toxic effects.
      Peak steady-state mRNA levels of the vitamin D-dependent calbindin-D9K gene were
      induced by 1,25(OH)2D more rapidly in the DBP-/- mice. Thus, the role of DBP is
      to maintain stable serum stores of vitamin D metabolites and modulate the rates
      of its bioavailability, activation, and end-organ responsiveness. These
      properties may have evolved to stabilize and maintain serum levels of vitamin D
      in environments with variable vitamin D availability.

PMID- 9916138
TI  - Trypsin activates pancreatic duct epithelial cell ion channels through proteinase
      activated receptor-2.
AB  - Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is
      cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds
      and activates the receptor. We examined the secretory effects of trypsin,
      mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct
      epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2,
      corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux
      inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited
      by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and
      inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of
      PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short
      circuit current from the basolateral, but not apical, surface of PDEC monolayers.
      In monolayers permeabilized basolaterally or apically with nystatin, AP activated
      apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in
      PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2
      expression on dog pancreatic ducts and PDEC was verified by immunofluorescence.
      Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate
      ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated,
      PAR-2-mediated ductal secretion may promote clearance of toxins and debris.

PMID- 9916139
TI  - Novel insight from transgenic mice into thyroid hormone resistance and the
      regulation of thyrotropin.
AB  - Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid
      hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or
      TSH) production. The molecular basis of this disorder resides in the dominant
      inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To
      determine the relative contributions of pituitary versus hypothalamic resistance
      to the dysregulated production of thyroid hormone in these patients, we developed
      a transgenic mouse model with pituitary-specific expression of a mutant TR
      (Delta337T). The equivalent mutation in humans is associated with severe
      generalized RTH. Transgenic mice developed profound pituitary resistance to
      thyroid hormone, as demonstrated by markedly elevated baseline and non
      triodothyronine (T3)-suppressible serum TSH and pituitary TSH-beta mRNA. Serum
      thyroxine (T4) levels were only marginally elevated in transgenic mice and
      thyrotropin-releasing hormone (TRH) gene expression in the paraventricular
      hypothalamus was downregulated. After TRH administration, T4 concentrations
      increased markedly in transgenic, but not in wild-type mice. Transgenic mice
      rendered hypothyroid exhibited a TSH response that was only 30% of the response
      observed in wild-type animals. These findings indicate that pituitary expression
      of this mutant TR impairs both T3-mediated suppression and T3-independent
      activation of TSH production in vivo. The discordance between basal TSH and T4
      levels and the reversal with TRH administration demonstrates that resistance at
      the level of both the thyrotroph and the hypothalamic TRH neurons are required to
      elevate thyroid hormone levels in patients with RTH.

PMID- 9916140
TI  - Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an
      animal model of multiple sclerosis.
AB  - Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a
      Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis
      and is characterized by infiltration of the central nervous system (CNS) by Th1
      cells and macrophages. Disease relapses are mediated by T cells specific for
      endogenous myelin epitopes released during acute disease, reflecting a critical
      role for epitope spreading in the perpetuation of chronic central CNS pathology.
      We asked whether blockade of the CD40-CD154 (CD40L) costimulatory pathway could
      suppress relapses in mice with established R-EAE. Anti-CD154 antibody treatment
      at either the peak of acute disease or during remission effectively blocked
      clinical disease progression and CNS inflammation. This treatment blocked Th1
      differentiation and effector function rather than expansion of myelin-specific T
      cells. Although T-cell proliferation and production of interleukin (IL)-2, IL-4,
      IL-5, and IL-10 were normal, antibody treatment severely inhibited interferon
      gamma production, myelin peptide-specific delayed-type hypersensitivity
      responses, and induction of encephalitogenic effector cells. Anti-CD154 antibody
      treatment also impaired the expression of clinical disease in adoptive recipients
      of encephalitogenic T cells, suggesting that CD40-CD154 interactions may be
      involved in directing the CNS migration of these cells and/or in their effector
      ability to activate CNS macrophages/microglia. Thus, blockade of CD154-CD40
      interactions is a promising immunotherapeutic strategy for treatment of ongoing T
      cell-mediated autoimmune diseases.

PMID- 9916141
TI  - The pulmonary circulation of homozygous or heterozygous eNOS-null mice is
      hyperresponsive to mild hypoxia.
AB  - Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension
      (PHTN) are unique properties of the pulmonary circulation. The pulmonary
      endothelium produces vasoactive factors, including nitric oxide (NO), that modify
      these phenomena. We tested the hypothesis that NO produced by endothelial nitric
      oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using
      mice with targeted disruption of the eNOS gene (eNOS-/-). Marked PHTN was found
      in eNOS-/- mice raised in mild hypoxia when compared with either controls or eNOS
      /- mice raised in conditions simulating sea level. We found an approximate
      twofold increase in partially and fully muscularized distal pulmonary arteries in
      eNOS-/- mice compared with controls. Consistent with vasoconstriction being the
      primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in
      normalization of RV pressure in eNOS-/- mice. In addition to studies of eNOS-/-
      mice, the dose-effect of eNOS was tested using heterozygous eNOS+/- mice.
      Although the lungs of eNOS+/- mice had 50% of normal eNOS protein, the response
      to hypoxia was indistinguishable from that of eNOS-/- mice. We conclude that eNOS
      derived NO is an important modulator of the pulmonary vascular response to
      chronic hypoxia and that more than 50% of eNOS expression is required to maintain
      normal pulmonary vascular tone.

PMID- 9916142
TI  - Molecular pharmacology of organic cation transporters in kidney.

PMID- 9916143
TI  - Suppression of inward-rectifying K+ channels KAT1 and AKT2 by dominant negative
      point mutations in the KAT1 alpha-subunit.
AB  - The Arabidopsis thaliana cDNA, KAT1 encodes a hyperpolarization-activated K+
      (K+in) channel. In the present study, we identify and characterize dominant
      negative point mutations that suppress K+in channel function. Effects of two
      mutations located in the H5 region of KAT1, at positions 256 (T256R) and 262
      (G262K), were studied. The co-expression of either T256R or G262K mutants with
      KAT1 produced an inhibition of K+ currents upon membrane hyperpolarization. The
      magnitude of this inhibition was dependent upon the molar ratio of cRNA for wild
      type to mutant channel subunits injected. Inhibition of KAT1 currents by the co
      expression of T256R or G262K did not greatly affect the ion selectivity of
      residual currents for Rb+, Na+, Li+, or Cs+. When T256R or G262K were co
      expressed with a different K+ channel, AKT2, an inhibition of the channel
      currents was also observed. Voltage-dependent Cs+ block experiments with co
      expressed wild type, KAT1 and AKT2, channels further indicated that KAT1 and AKT2
      formed heteromultimers. These data show that AKT2 and KAT1 are able to co
      assemble and suggest that suppression of channel function can be pursued in vivo
      by the expression of the dominant negative K+in channel mutants described here.

PMID- 9916144
TI  - Inhibition of vacuolar ion channels by polyamines.
AB  - In this work, direct effects of cytosolic polyamines on the two principle
      vacuolar ion channels were studied by means of patch-clamp technique. Fast and
      slow activating vacuolar channels were analyzed on membrane patches isolated from
      vacuoles of the red beet taproot. The potency of the fast and of the slow
      vacuolar channel blockage by polyamines decreased with a decrease of the
      polycation charge, spermine4+ > spermidine3+ > putrescine2+. In contrast to the
      inhibition of the fast vacuolar channel, the blockage of the slow vacuolar
      channel by polyamines displayed a pronounced voltage-dependence. Hence, in the
      presence of high concentration of polyamines the slow vacuolar channel was
      converted into a strong inward rectifier as evidenced by its unitary current
      voltage characteristic. The blockage of the slow vacuolar channel by polyamines
      was relieved at a large depolarization, in line with the permeation of polyamines
      through this channel. The voltage-dependence of blockage was analyzed in terms of
      the conventional model, assuming a single binding site for polyamines within the
      channel pore. Taking advantage of a simple linear structure of naturally
      occurring polyamines, conclusions on a possible architecture of the slow vacuolar
      channel pore were drawn. The role of common polyamines in regulation of vacuolar
      ion transport was discussed.

PMID- 9916146
TI  - Electrokinetic properties of the sarcoplasmic reticulum membrane obtained from
      reconstitution studies.
AB  - Electrophoretic mobility data of SR vesicles reconstituted with uncharged and two
      mixtures of charged and uncharged lipids (Brethes, D., Dulon, D., Johannin, G.,
      Arrio, B., Gulik-Krzywicki, T., Chevallier, J. 1986. Study of the electrokinetic
      properties of reconstituted sarcoplasmic reticulum vesicles. Arch. Biochem.
      Biophys. 246:355-356) were analyzed in terms of four models of the membrane-water
      interface: (I) a smooth, negatively charged surface; (II) a negatively charged
      surface of lipid bilayer covered with an electrically neutral surface frictional
      layer; (III) an electrically neutral lipid bilayer covered with a neutral
      frictional layer containing a sheet of negative charge at some distance above the
      surface of the bilayer; (IV) an electrically neutral lipid bilayer covered with a
      homogeneously charged frictional layer. The electrophoretic mobility was
      predicted from the numerical integration of Poisson-Boltzmann and Navier-Stokes
      equations. Experimental results were consistent only with predictions based on
      Model-III with charged sheet about 4 nm above the bilayer and frictional layer
      about 10 nm thick. Assuming that the charge of the SR membrane is solely due to
      that on Ca++-ATPase pumps, the dominant SR protein, the mobility data of SR and
      reconstituted SR vesicles are consistent with 12 electron charges/ATPase. This
      value compares well to the net charge of the cytoplasmic portion of ATPase
      estimated from the amino acid sequence (-11e). The position of the charged sheet
      suggests that the charge on the ATPase is concentrated in the middle of the
      cytoplasmic portion. The frictional layer of SR can be also assigned to the
      cytoplasmic portion of Ca++-ATPase. The layer has been characterized with
      hydrodynamic shielding length of 1. 1 nm. Its thickness is comparable to the
      height of the cytoplasmic portion of Ca++-ATPase.

PMID- 9916145
TI  - Characteristics of current fluctuations originating from activities of inward
      rectifier K+ channels in guinea-pig heart cells.
AB  - Although outward current through inward-rectifier K+ channels has been observed
      in the whole-cell mode of the patch-clamp technique, no outward unitary current
      in single-channel studies has been recorded with the physiological ionic
      conditions. Hence, the relationship between single-channel activities and the
      inward rectification of the whole-cell current has been poorly understood.
      Therefore, characteristics of inward-rectifier K+ channels in guinea-pig
      ventricular myocytes were assessed by the noise analysis of the K+ current using
      the whole-cell patch clamp method. Partial blockade of the inward-rectifier K+
      current by Ba2+ was used to obtain different levels of mean current and current
      fluctuation as needed for variance-to-mean analysis. The plot of variance of
      current fluctuation against mean currents was well fitted by theoretical
      parabolic curves, and the unitary conductance, the open probability, and the
      density of functional channels were deduced. The unitary conductance of the
      inward-rectifier K+ channel exhibited an inward-rectification, although the
      channel open probability and the density of functional channels were not much
      different at various holding potentials used. The unitary conductance was not
      changed when the intrapipette concentration of Mg2+ was reduced, but tended to be
      smaller when the pipette contained high Mg2+ concentration. Spermine also tended
      to reduce the outward unitary conductances, although the reduction was not
      statistically significant. These results suggest that the inward rectification in
      the whole-cell current was due to the inward-rectifying property of the unitary
      conductance of the K+ channels. Inward rectification of the unitary conductance
      may be caused by blocking of the channels by both Mg2+ and polyamines.

PMID- 9916147
TI  - Sphingomyelins of rat liver: biliary enrichment with molecular species containing
      16:0 fatty acids as compared to canalicular-enriched plasma membranes.
AB  - We harvested canalicular-enriched plasma membranes of hepatocytes and collected
      fistula bile from male rats and isolated the sphingomyelins. Following
      sphingomyelinase hydrolysis, we identified the sphingomyelin molecular species on
      the basis of their benzoylated ceramide derivatives employing high performance
      liquid chromatography. Sphingomyelin constitutes </=3% of total biliary
      phospholipids (which are mostly sn-1 16:0 long-chain phosphatidylcholines) and
      approximately 30% of canalicular-enriched membranes. In both cases, the principal
      molecular species were composed of 16:0, 18:0, 20:0, 22:0, 23:0, 24:0, 24:1 and
      24:2 fatty acid classes. However, the 16:0 fatty acid species was enriched in
      biliary sphingomyelin to a significantly greater degree than in sphingomyelins of
      canalicular-enriched plasma membranes (46% vs. 25% of total). We argue a physical
      chemical case for laterally separated domains of very long chain sphingomyelins
      on the exoplasmic leaflet of the canalicular membrane. We bolster our hypothesis
      by the likelihood that the least hydrophobic, e.g., 16:0 sphingomyelin molecular
      species, are miscible with biliary phosphatidylcholines, and are secreted into
      bile. Laterally separated domains of very long chain sphingomyelins on the
      exoplasmic leaflet of the canalicular membrane could provide a means of
      sequestering cholesterol molecules prior to secretion into bile.

PMID- 9916148
TI  - Effects of mutations in proline 345 on insertion of diphtheria toxin into model
      membranes.
AB  - Translocation of the catalytic domain of diphtheria toxin (DT) across the
      endosomal membrane to the cytoplasm of mammalian cells requires the low-pH
      dependent insertion of a hydrophobic helical hairpin (TH8-TH9) that is buried
      within the T domain of the native protein. Mutations of Pro345, which terminates
      helix TH8, have been reported to block toxicity for Vero cells. We found that
      mutant toxins in which Pro345 had been replaced by Cys, Glu, or Gly were
      profoundly defective at low pH in forming channels in planar phospholipid
      bilayers and in permeabilizing phospholipid vesicles to entrapped fluorophores.
      Experiments with isolated T domain containing a polarity-sensitive fluorophore
      attached to Cys at position 332 suggest that the P345E mutation blocks membrane
      insertion. None of the Pro345 mutations shifted the pH-dependence of binding in
      solution of the hydrophobic fluorophore, 2-p-toluidinyl-naphthalene 7-sulfonate.
      The results indicate that proline at position 345 is required for the T domain to
      insert into phospholipid bilayers or to adopt a functional conformation within
      the bilayer.

PMID- 9916149
TI  - Cytoplasmic determinants of piperidine blocking affinity for N-type calcium
      channels.
AB  - Piperidines are a relatively novel class of calcium channel blockers which act at
      a unique receptor site associated with the calcium channel alpha1 subunit.
      Calcium channel blocking affinities ranging from subnanomolar to several hundred
      micromolar have been reported in the literature, suggesting that piperidine block
      is highly sensitive to the cellular environment experienced by the channel. Here,
      I have investigated some of the cytoplasmic determinants of haloperidol block of
      N-type calcium channels expressed in human embryonic kidney cells. In perforated
      patch clamp recordings, haloperidol blocks N-type calcium channels with an
      inhibition constant of 120 microM. Upon internal dialysis with chloride
      containing pipette solution, the blocking affinity increases by 40-fold. This
      effect could be attributed in part to the presence of internal chloride ions, as
      replacement of intracellular chloride with methanesulfonate reduced haloperidol
      blocking affinity by almost one order of magnitude. Tonic inhibition of N-type
      channels by Gbetagamma subunits further enhanced the blocking effects of
      haloperidol, suggesting the possibility of direct effects of Gbetagamma binding
      on the local environment of the piperidine receptor site. Overall, depending on
      the cytoplasmic environment experienced by the channel, the blocking affinity of
      N-type calcium channels for haloperidol may vary by more than two orders of
      magnitude. Thus, absolute blocking affinities at the piperidine receptor site
      must be interpreted cautiously and in the context of the particular experimental
      setting.

PMID- 9916150
TI  - ATP-induced inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney
      cells: lack of involvement of known purinoceptor-coupled signaling pathways.
AB  - P2U/2Y-receptors elicit multiple signaling in Madin-Darby canine kidney (MDCK)
      cells, including a transient increase of [Ca2+]i, activation of phospholipases C
      (PLC) and A2 (PLA2), protein kinase C (PKC) and mitogen-activated protein kinase
      (MAPK). This study examines the involvement of these signaling pathways in the
      inhibition of Na+,K+,Cl- cotransport in MDCK cells by ATP. The level of ATP
      induced inhibition of this carrier ( approximately 50% of control values) was
      insensitive to cholera and pertussis toxins, to the PKC inhibitor calphostin C,
      to the cyclic nucleotide-dependent protein kinase inhibitors, H-89 and H-8 as
      well as to the inhibitor of serine-threonine type 1 and 2A phosphoprotein
      phosphatases okadaic acid. ATP led to a transient increase of [Ca2+]i that was
      abolished by a chelator of Ca2+i, BAPTA. However, neither BAPTA nor the Ca2+
      ionophore A231287, or an inhibitor of endoplasmic reticulum Ca2+-pump,
      thapsigargin, modified ATP-induced inhibition of Na+,K+, Cl- cotransport. An
      inhibitor of PLC, U73122, and an inhibitor of MAPK kinase (MEK), PD98059, blocked
      ATP-induced inositol-1,4, 5-triphosphate production and MAPK phosphorylation,
      respectively. However, these compounds did not modify the effect of ATP on
      Na+,K+, Cl- cotransport activity. Inhibitors of PLA2 (AACOCF3), cycloxygenase
      (indomethacin) and lypoxygenase (NDGA) as well as exogenous arachidonic acid also
      did not affect ATP-induced inhibition of Na+,K+,Cl- cotransport. Inhibition of
      the carrier by ATP persisted in the presence of inhibitors of epithelial Na+
      channels (amiloride), Cl- channels (NPPB) and Na+/H+ exchanger (EIPA) and was
      insensitive to cell volume modulation in anisosmotic media and to depletion of
      cells with monovalent ions, thus ruling out the role of other ion transporters in
      purinoceptor-induced inhibition of Na+,K+,Cl- cotransport. Our data demonstrate
      that none of the known purinoceptor-stimulated signaling pathways mediate ATP
      induced inhibition of Na+,K+,Cl- cotransport and suggest the presence of a novel
      P2-receptor-coupled signaling mechanism.

PMID- 9916151
TI  - Human ribonucleases.
AB  - This review considers the distribution in the body, catalytic properties, and
      certain structural characteristics of human ribonucleases. It also gives a brief
      review of their biological functions and possible fields of their application.

PMID- 9916152
TI  - Hormones as life regulators in the current molecular endocrinology.
AB  - This review considers results of studies on six hormones-- leptin,
      adrenomedullin, parathyroid hormone-related protein, vascular endothelium growth
      factor, fibroblast growth factor 2, and prolactin. Genes of these hormones are
      markedly expressed in various tissues which can synthesize and release the
      corresponding hormones into the intercellular space and blood. The structure of
      hormone receptor genes and their expression in various tissues which are target
      organs of the hormones are discussed. All organs, tissues, and cells of the body
      are concluded to be endocrine and releasing their specific hormones into blood.
      Hormones regulate vital processes, provide communications between organs and
      tissues, and integrate them into a united entity. All hormones are
      multifunctional compounds of wide spectrum of biological activities. The
      regulation of gene expression via various mechanisms is a common property of all
      hormones. Many tissue-specific hormones are yet to be discovered.

PMID- 9916154
TI  - Generation of sanazole nitro radicals by xanthine oxidase.
AB  - The formation of sanazole (drug AK-2123) radicals by the xanthine--xanthine
      oxidase system was studied by spectrophotometry in hypoxygenic (pO2 = 45 +/- 5 mm
      Hg) and normoxygenic (pO2 = 150 +/- 4 mm Hg) media. At concentrations from 0.1 to
      10.5 mM, sanazole dose-dependently increased the rate of cytochrome c reduction
      in hypoxygenic medium but had no effect on the reaction rate under normoxygenic
      conditions. The activating influence of sanazole depended on xanthine
      concentration. At xanthine concentrations from 0.08 to 0.1 mM in hypoxygenic
      medium, the rate of cytochrome c reduction was increased twofold after the
      addition of sanazole. Reduction of cytochrome c in the medium without sanazole
      was completely blocked by superoxide dismutase; addition of sanazole partially
      restored the blocked reaction. Cytochrome c reduced in the presence of superoxide
      dismutase and sanazole was oxidized by cytochrome oxidase. The data indicate that
      in the presence of the xanthine--xanthine oxidase system under hypoxygenic
      conditions, sanazole can accept electrons and generate nitro radicals which
      donate electrons to cytochrome c or oxygen.

PMID- 9916153
TI  - Inhibitors of mitochondrial energy production prevent DNA internucleosomal
      fragmentation in thymocytes.
AB  - Apoptosis or programmed cell death is a gene-controlled process of cell self
      destruction. One of the earliest manifestations of apoptosis, which precedes
      morphological changes, is a decrease of mitochondrial membrane potential. Here we
      show that neither inhibitors of the mitochondrial respiratory chain (rotenone and
      antimycin) nor an uncoupler of oxidative phosphorylation (carbonyl cyanide m
      chlorophenylhydrazone), agents which decrease the mitochondrial membrane
      potential, induce DNA internucleosomal fragmentation, but all of them markedly
      prevent fragmentation induced either by glucocorticoids or the Ca2+ ionophore
      A23187. A similar effect was also observed in the presence of a mitochondrial
      ATPase inhibitor (oligomycin). The inhibition of DNA internucleosomal
      fragmentation can be explained by the ability of inhibitors to prevent the
      mitochondrial permeability transition--a key event in apoptosis induction.

PMID- 9916155
TI  - Determination of time-dependent shape changes in red blood cells.
AB  - A kinetic method for detecting changes in red blood cell shape with time
      resolution on the order of seconds is described. The definition of shape index
      (SI) and the experimental conditions under which the measurements should be
      conducted are given, and the relationship between SI and morphological index,
      which is often used to quantitatively assess red blood cell morphology, is
      established. Further, we show that the method can be used to assess shape changes
      under a variety of experimental conditions known to cause major perturbations in
      the morphology of red blood cells (such as addition of lysolecithin or
      chlorpromazine) and to detect changes in shape during chemical fixation for
      observation with microscopy. We report here that the ability of glutaraldehyde to
      fix red blood cells without additional alteration in shape strongly depends on
      the morphology that is being fixed and the initial state of the cells.

PMID- 9916156
TI  - Specificity of self-assembly of cytochrome P450.
AB  - Under certain conditions, hexamers of microsomal cytochrome P450 can self
      assemble from the subunits of different isoforms. However, the possibility for
      free choice results in recognition between identical subunits of each form of
      cytochrome P450 which provides preferential association of identical monomers
      into corresponding hexamers. The specificity of self-assembly suggests hexameric
      arrangement of cytochrome P450 in native membranes as we proposed earlier. In the
      present study, highly purified cytochrome P450 2B4 and cytochrome P450 1A2 (CYP
      2B4 and CYP 1A2), including those immobilized by covalent attachment to an
      insoluble carrier of one protomer of each hexamer, were employed.

PMID- 9916157
TI  - Role of autophosphorylation in regulation of protein kinase CK2 from rat neuronal
      chromatin.
AB  - The regulation of rat brain cortex protein kinase CK2 (casein kinase 2) by
      autophosphorylation has been investigated. Purified CK2 from rat neuronal
      chromatin is composed of two regulatory (beta) and two catalytic (alpha and/or
      alpha;) subunits. The molecular masses of the subunits--43 (alpha), 39 (alpha;),
      and 25 kD (beta)--were similar to those of typical CK2 subunits. A significant
      amount of alpha;-subunit occurred in neuronal chromatin; the molar ratios for the
      subunits were 1.1:0.9:1.9. Pharmacological probes (derivatives of 4,5-di(N
      methylcarbamoyl)-1-alkyl-imidazole) were used to study autophosphorylation of
      separate subunits. These compounds have different effects on neuronal chromatin
      CK2, transcription, and neurological memory. Changes in the autophosphorylation
      of the CK2 subunits were found with the help of these compounds. Inhibitors of
      transcription decreased the beta-subunit autophosphorylation. Stimulators of
      transcription increased the beta-subunit autophosphorylation and promoted the
      autophosphorylation of the alpha; (but not the alpha) subunit. The beta-subunit
      autophosphorylation led to reduction in phosphorylation of nonhistone HMG 14
      protein that has been shown to be a physiological substrate of CK2. The
      autophosphorylation of the alpha;-subunit raised the CK2 activity with HMG 14.
      The question of functional distinctions between the alpha;- and alpha-subunits of
      chromatin CK2 in differentiated neurons is discussed.

PMID- 9916158
TI  - Formation and distribution of modified FAD between isozymes of alcohol oxidase in
      the methylotrophic yeast pichia methanolica.
AB  - The content of modified FAD (mFAD) in isoforms of alcohol oxidase (AO) in the
      methylotrophic yeast Pichia methanolica MH4 is increased in the stationary growth
      phase of the culture or under lower dilution rates. The isoform with slower
      electrophoretic mobility has the higher mFAD content. The results of in vitro
      experiments and the occurrence of mFAD in AO-lacking mutants of Hansenula
      polymorpha DL-1 imply a biosynthetic origin of this cofactor. HPLC analysis of
      tryptic hydrolysates of the first and the ninth isoforms of AO from P.
      methanolica MH4 revealed two different types of subunits. Possible mechanism of
      mFAD formation and distribution between the AO isozymes is discussed.

PMID- 9916159
TI  - Effect of nitrite on primary photosynthetic processes in isolated chloroplasts of
      wheat grown under various conditions of nitrogen supply.
AB  - In wheat chloroplasts, NO2- (5 mM) inhibited non-cyclic phosphorylation coupled
      to the linear electron flow through both photosystems but stimulated cyclic
      phosphorylation with phenazine methosulfate (plus diuron) and electron flux from
      an artificial electron donor through PSI and methylviologen to oxygen. During
      light energization of chloroplasts, NO2- increased the F740/F695 ratio in the low
      temperature fluorescence spectra, thus suggesting that the energy of absorbed
      quanta is redistributed in favor of PSI. Nitrite also stimulated the activity of
      Mg2+-dependent H+-ATPase. Changes in the slow component of the induction curve of
      delayed fluorescence also suggest that NO2- affects energy transformation
      processes that are coupled to electron transport in the chloroplasts. Nitrite had
      no effect on these functional characteristics of thylakoids and chloroplasts
      isolated from plants grown under nitrogen deficiency in the medium.

PMID- 9916160
TI  - Purification and characterization of P33 protein of Candida utilis homologous to
      bgl2p of Saccharomyces cerevisiae; comparative analysis of the role of these
      proteins in molecular organization of the yeast cell walls.
AB  - P33 protein was isolated from the cell walls of Candida utilis. Homology between
      P33 and Bgl2p proteins from the cell walls of Saccharomyces cerevisiae was shown.
      The important role of these proteins in molecular organization of yeast cell
      walls was demonstrated using trypsin proteolysis and the "gene disruption"
      method.

PMID- 9916161
TI  - A site-specific endonuclease from thermophilic strain Bacillus species ZE is a
      ClaI isoschizomer.
AB  - Strain Bacillus species ZE with a maximal yield of the ClaI isoschizomer was
      chosen from 12 natural thermophilic strains producing ClaI isomers. The yield is
      110 times higher than that of the ClaI prototype endonuclease from Caryophanon
      latum L. The enzyme is sensitive to DNA dam-methylation and is highly stable
      under storage.

PMID- 9916162
TI  - Immunoreactivity of apolipoprotein B-100 and binding to LDL-receptor of
      phospholipase A2-treated low density lipoproteins.
AB  - Lipid--protein particles were obtained by treatment of low density lipoproteins
      (LDL) with phospholipase A2 from bee venom. Under these conditions, half of the
      phosphatidylcholine (PC) of LDL was changed to lysophosphatidylcholine (LPC). At
      the same time, the composition of other lipids and the apoprotein structure were
      unaffected. Three monoclonal antibodies (MAbs) against various apo B epitopes
      were used to test immunoreactivity of phospholipase A2-treated LDL (pl-LDL). The
      apo B epitope interacting with MAb 4C11 (amino acid residues 2377-2658) showed
      significantly decreased immunoreactivity. Increase in MAb 4C11 binding was
      demonstrated to depend on oxidation degree of LDL. Thus, changing of half of PC
      to LPC modified apo B translocation in the lipoprotein globule in an opposite
      manner as compared with changes induced by oxidative modification. A minor
      increase in immunoreactivity of pl-LDL with 1D1 MAb against a large middle part
      of apo B (residues 1297-3249) may be due to the effect of the change of surface
      lipid composition on the extent of immersion of apo B into the hydrophobic phase.
      No changes in the interaction of pl-LDL with MAb 2G8 (residues 3748-4306) were
      observed in comparison with native LDL. This fact demonstrates that 50%
      phospholipolysis of LDL does not affect the expression of apo B C-terminal
      residues in pl-LDL. Twofold increase in pl-LDL affinity to immobilized LDL
      receptor was shown in contrast to LDL. The data indicate that LPC accumulation in
      LDL results in better elimination of LDL from the blood stream than in case of
      accumulation of oxidative products.

PMID- 9916163
TI  - Possible role of reactive oxygen species in antiviral defense.
AB  - The role of reactive oxygen species (ROS) participating in antiviral host defense
      is considered. Unlike antibacterial defense, when ROS and their derivatives act
      as biological weapons killing pathogenic bacteria, the function of ROS in the
      antiviral defense is assumed to be mediated by apoptosis. It is suggested that a
      cell activates generation of superoxide and hydrogen peroxide by xanthine oxidase
      as well as by intracellular NADPH-oxidase in response to appearance of a virus in
      its cytoplasm. Increase in ROS level turns on the process of programmed cell
      death in the infected cells. Moreover, H2O2 diffuses into the adjacent cells (due
      to its high membrane permeability), also inducing apoptosis (death of bystander
      cells). So, the infected cell and its neighbors (which are the most likely to be
      infected) are eliminated, thus blocking the spreading of the viral infection.

PMID- 9916164
TI  - Is one amino acid responsible for substrate specificity of monoamine oxidase A
      and B?
AB  - Mutation of Phe-208 for Ile in monoamine oxidase (MAO) A and mutation of Ile-199
      for Phe in MAO B inverted substrate specificity and inhibitor selectivity of the
      mutants towards the opposite form of the enzyme, MAO B and MAO A, respectively
      (Y. Tsugeno and A. Ito (1997) J. Biol. Chem., 272, 14033-14036). However,
      according to data presented by Tsugeno and Ito such point mutations did alter
      kinetic characteristics of oxidative deamination of some but not all substrates.
      These point mutations did not alter the secondary structure evaluated by four
      computer methods. Analysis of the efficacy of a few series of inhibitors suggests
      spatial differences of substrate binding sites of MAO A and MAO B. All these
      discrepancies indicate that one amino acid can be responsible for binding of some
      but not all substrates and inhibitors.

PMID- 9916165
TI  - Pseudoprimers cause somatic hypermutation of Ig genes.
AB  - It is proposed that hypermutation of the Ig gene is based on the use of
      "misprimers" (MPs) capable of competing with a true primer for the DNA. The MP is
      a product of the cleavage of the nascent transcript. Each MP has an erroneous
      base on its 3; terminus. Wobbling of the unpaired 3; end of the MP forces the DNA
      polymerase to make an error.

PMID- 9916166
TI  - Carriers that concentrate native bone morphogenetic protein in vivo.
AB  - It is well known that the native bone morphogenetic protein (BMP) complex is much
      more active than each of its components: the concentration needed for
      extraskeletal bone induction is about a thousand times higher for a specific
      rhBMP than for the native BMP complex as a whole. Since the patient's own body is
      capable of producing the native BMP complex, the interesting question arises
      whether it is feasible to develop specific implants that concentrate native BMPs
      to levels that allow bone induction to take place. Such BMP-concentrating
      implants differ from carriers that are meant to passively store and deliver
      rhBMP. The fact that the native BMP complex is much more active than each of its
      constituent BMP molecules (the required concentration for the native complex is
      up to a thousand times lower) makes the question even more of interest. Based on
      the literature, the concept is developed in this article that selected implants,
      through mineralization in vivo, can concentrate the patient's own native BMP
      complex.

PMID- 9916167
TI  - New technique to extend the useful life of a biodegradable cartilage implant.
AB  - Biodegradable implants made of alpha-hydroxypolyesters, such as polylactic acid,
      polyglycolic acid, or their copolymers, undergo bulk degradation with a
      concomitant mass loss. Although biocompatibility or toxicity problems, which have
      occasionally been reported in response to these materials' in vivo behavior, have
      not been conclusively linked to rapid mass loss, we hypothesized that such
      implants should degrade and lose mass in a more uniform rate. To this end, we
      designed a new implant, intended to be used in articular cartilage repair,
      consisting of a blend of three copolymers of 50:50 poly(d,l)-lactide coglycolide
      with inherent viscosities of 0.23, 0.58, and 1.37 dL/g. The objective of the
      blend implant design was to achieve a slower rate of degradation and mass loss in
      comparison to a previous design, which used a single copolymer of inherent
      viscosity of 0.58 dL/g. The blend's in vitro degradation characteristics were
      obtained and compared to those of the control design in terms of mass, molecular
      weight, pH, mechanical properties, gross morphology, and porosity. Another
      objective of our study was to design and employ a novel test for assessing the
      permeability of porous scaffolds, using a custom apparatus under direct
      permeation conditions. Significant differences in the temporal behavior of the
      two groups were found. The blend implants maintained their overall structural
      integrity longer than control specimens (6 weeks versus 3 weeks). This was a
      surprising finding in light of the fact that losses in molecular weight were
      similar in the two groups. Extension of structural usefulness to 6 weeks,
      achieved by the method described in the study, can be expected to enhance the
      viability of this scaffold in an in vivo application such as cartilage repair.
      Thus, the blended copolymer implants may be more suitable in orthopedic
      applications, where a decreased degradation rate would be preferable.

PMID- 9916168
TI  - In vivo degradation and release kinetics of chloramphenicol-loaded poly(D,L)
      lactide sponges.
AB  - Poly(d,l)-lactide (PDLLA) homopolymer, with an average molecular weight of 20,000
      daltons, was produced by the ring-opening polymerization of d,l-lactide in the
      presence of SnCl(2).2H(2)O as the catalyst. The PDLLA sponges loaded with
      chloramphenicol were prepared by a solvent evaporation technique. The drug
      loadings achieved were 14.84 and 25.23 mg for the PDLLA sponges with 35 and 70 mg
      total weights, respectively. These sponges were implanted in Wistar rats, and in
      vivo degradation, drug release, and tissue reactions were followed. The PDLLA
      sponges carrying no drug degraded with time linearly. Almost 80% of the sponges
      were degraded in about 180 days. While the drug-loaded PDLLA sponges were
      degraded much faster in 4 weeks (about 35% of the matrix was degraded), then the
      degradation slowed down significantly. Drug release from the sponges was parallel
      to the degradation. Almost 60% of the loaded drug released in 4 weeks. There were
      no acute inflammatory reactions in the initial period, either for the plain or
      for the drug-loaded PDLLA sponges. Macrophages and multinuclear giant cells start
      to appear after 7 days of implantation. The fibroblastic activity also started
      after the same period. After that, there were decreases in the number of some
      cells (neutrophils, lymphocytes, and macrophages), while multinuclear giant cells
      and fibroblastic activities gradually increased. Granulation tissue started at
      about 1 month, and new connective tissue was gradually formed until 180 days of
      implantation. There were significant numbers of inflammatory cells after 60 days,
      which were replaced by fibroblasts after 180 days. There was almost no
      significant neovascularization after 180 days, but implant fragmentation
      gradually increased (which slows the degradation) with time. It was concluded
      that this novel drug release sponge may be safely and effectively used as an
      active soft tissue-filling material.

PMID- 9916169
TI  - Partition and diffusion of sodium and chloride ions in soft charged foam: the
      effect of external salt concentration and mechanical deformation.
AB  - The partition and diffusion characteristics of an acrylic acid/acrylamide
      hydrogel, copolymerized in the pores of a polyurethane foam with sodium and
      chloride ions, were studied by radiochemical methodologies. The hydrogel foam
      swells by 51%, 80%% and 260% relative to its raw state under bath salt
      concentrations of 2.0, 1.0, and 0.15 M, respectively. The corresponding partition
      coefficients are 1.13, 1.29, and 1.99 for sodium (Na+) and 0.89, 0. 85, and 0.65
      for chloride (Cl-). The diffusion coefficients are independent of bath
      concentration and increase linearly with hydration towards their values in water.
      Deformation affects partition and diffusion solely by dilatation, which
      determines the swelling and hydration. Comparison of the hydrogel foam with
      cartilage and intervertebral disc shows considerable similarities and suggests
      that the same mechanisms control their function.

PMID- 9916170
TI  - Small intestinal submucosa: a rapidly resorbed bioscaffold for augmentation
      cystoplasty in a dog model.
AB  - The extracellular matrix (ECM) of porcine small intestinal submucosa (SIS) has
      been shown to serve as a resorbable scaffold for tissue repair and remodeling in
      several body locations including the urinary bladder. The rate of resorption and
      extent of SIS degradation are unknown. Nine dogs were divided into three equal
      groups. Approximately 40% of the anterior dome of the urinary bladder was
      resected in each dog and replaced with porcine SIS. One group of dogs was
      sacrificed at each of 4, 8, and 12 weeks after surgery and the fate of the
      implanted SIS determined by immunohistochemical methods using a monoclonal
      antibody specific for porcine-derived SIS. By 4 weeks after surgery, only
      scattered remnants of SIS were present in the remodeled urinary bladder and these
      positively staining foci were surrounded by an extensive new host derived ECM and
      neovascularization. There was a continuous layer of transitional epithelium on
      the luminal surface by 4 weeks. No evidence for the originally implanted SIS
      could be found at either 8 or 12 weeks and bundles of organized smooth muscle
      cells were present at the operative site. In summary, SIS is rapidly and
      extensively degraded when used as a bioscaffold for augmentation cystoplasty in
      the dog model.

PMID- 9916171
TI  - Evaluation of the viscoelastic properties of pharyngeal tissue.
AB  - The viscoelastic properties of the human pharyngeal tissue in tension were
      evaluated, based on both an experimental protocol-consisting of cyclic load,
      tensile stress relaxation, and incremental step load tests-and a quasilinear
      viscoelastic theory. The physical properties of the pharyngeal tissue were
      evaluated to facilitate the biomechanical modeling of human pharynx. The
      methodology described has potentially significant clinical importance when one
      considers engineering a similar type of tissue having the same material
      properties in the future. Qualitatively, the characteristic features of
      viscoelastic properties of human pharyngeal tissue were experimentally obtained.
      Then, the reduced stress relaxation function and the elastic response of the
      pharyngeal tissue were derived from the experimental results specifically
      obtained from this tissue, by applying the quasilinear viscoelastic theory. The
      mathematical expression for analyzing nonlinear viscoelastic properties of human
      pharyngeal tissue is presented, as is the experimental protocol to evaluate the
      tissue properties. The characteristic features of the tissue need to be
      considered when attempting to engineer this tissue equivalent, and the data
      generated can be utilized to evaluate the function of tissue when it is
      engineered.

PMID- 9916172
TI  - Three-dimensional fibroblast culture implant for the treatment of diabetic foot
      ulcers: metabolic activity and therapeutic range.
AB  - Dermagraft is three-dimensional, allogeneic, human neonatal dermal fibroblast
      culture grown on a degradable scaffold and cryopreserved. Clinical trials for
      treatment of diabetic foot ulcers showed optimal healing within a therapeutic
      range of metabolic activity, determined by 3[4,5-dimethylthiazol-2-yl]2,5
      diphenyltetrazolium bromide (MTT) reduction. Actions of Dermagraft in wound
      repair include colonization by cells and provision of growth factors and
      cytokines, both activities dependent on living cells. Cells in the cryopreserved
      culture showed 60% viability by dye exclusion and, when isolated, were able to
      proliferate in monolayer culture. Protein synthesis by Dermagraft was inhibited
      70-98% by cryopreservation, but, if within the therapeutic range, recovered to 45
      85% of the prefreeze value over 48 h. Subtherapeutic Dermagraft showed variable,
      low recovery. Expression of mRNA for vascular endothelial growth factor (VEGF),
      platelet-derived growth factor A chain, and insulin-like growth factor-1 was
      reduced >83% in subtherapeutic compared with therapeutic Dermagraft. Granulocyte
      colony-stimulating factor and VEGF protein secretion, determined by enzyme-linked
      immunosorbent assay (ELISA), and angiogenic activity also depended on therapeutic
      range. VEGF secretion dropped sharply with MTT reductase in subtherapeutic
      tissue. The data demonstrate the critical dependence of the therapeutic
      properties of this living dermal implant on recovery of protein synthesis, growth
      factor expression, and angiogenesis, determined by metabolic activity.

PMID- 9916173
TI  - Chondrogenic differentiation of cultured human mesenchymal stem cells from
      marrow.
AB  - In the adult human, mesenchymal stem cells (MSCs) resident in bone marrow retain
      the capacity to proliferate and differentiate along multiple connective tissue
      lineages, including cartilage. In this study, culture-expanded human MSCs (hMSCs)
      of 60 human donors were induced to express the morphology and gene products of
      chondrocytes. Chondrogenesis was induced by culturing hMSCs in micromass pellets
      in the presence of a defined medium that included 100 nM dexamethasone and 10
      ng/ml transforming growth factor-beta(3) (TGF-beta(3)). Within 14 days, cells
      secreted an extracellular matrix incorporating type II collagen, aggrecan, and
      anionic proteoglycans. hMSCs could be further differentiated to the hypertrophic
      state by the addition of 50 nM thyroxine, the withdrawal of TGF-beta(3), and the
      reduction of dexamethasone concentration to 1 nM. Increased understanding of the
      induction of chondrogenic differentiation should lead to further progress in
      defining the mechanisms responsible for the generation of cartilaginous tissues,
      their maintenance, and their regeneration.

PMID- 9916174
TI  - Repair of large full-thickness articular cartilage defects with allograft
      articular chondrocytes embedded in a collagen gel.
AB  - Full-thickness articular cartilage defects are a major clinical problem; however,
      presently there is no treatment available to regeneratively repair these lesions.
      The current therapeutic approach is to drill the base of the defect to expose the
      subchondral bone with its cells and growth factors. This usually results in a
      repair tissue of fibrocartilage that functions poorly in the loaded joint
      environment. The use of phenotypically appropriate chondrocytes embedded in a
      collagen gel delivery vehicle may provide a method that could be used to repair
      full-thickness articular cartilage defects with functionally satisfactory hyaline
      cartilage. Allograft articular chondrocytes embedded in a type I collagen gel
      were transplanted into large (6 x 3 x 3 mm), full-thickness articular cartilage
      defects in condylar and patellar weight-bearing surfaces to develop clinically
      applicable methods to repair articular cartilage defects. Chondrocytes were
      isolated from the articular cartilage of 4-week-old New Zealand rabbits and
      embedded in type I collagen gels. This composite was transplanted into a full
      thickness defect on the medial femoral condyle and patellar groove of adolescent
      host rabbits. The repair cartilage was assessed histologically by a
      semiquantitative scoring system and biomechanically with a microindentation
      technique of specimens 4-48 weeks after chondrocyte transplantation. Defects in
      both locations were repaired with histologically apparent hyaline cartilage
      observed from as early as 4 weeks until 48 weeks after transplantation. The
      repair cartilage in the medial femoral condyle was more irregular than in the
      patellar groove, but in all other respects was similar. The grafted tissue did
      not remodel and differentiate into the morphological zones seen in normal
      articular cartilage. No tidemark or subchondral bony plate formed even 48 weeks
      after transplantation. Biomechanically, the repaired cartilage demonstrated
      indentation values similar to normal articular cartilage 12 weeks after
      transplantation and remained the same 48 weeks after transplantation. By
      contrast, the control (i.e., empty) defects healed with tissue that exhibited
      very poor metachromatic staining and exhibited very high indentation values.
      Incomplete bonding of the repair tissue to the normal cartilage was seen, and the
      surface was significantly irregular with major discontinuities. These
      observations provide the basis for considering the use of allograft articular
      chondrocytes to repair articular cartilage defects in the weight-bearing regions
      of the knee.

PMID- 9916175
TI  - "Come out, come out wherever you are": the Food and Drug Administration's
      proposed rule on establishment registration and listing for manufacturing of
      human cellular and tissue-based products.

PMID- 9916177
TI  - From Molecules to Marathons: The Wisdom of Our Past Presidents. Introduction to
      the Symposium.

PMID- 9916176
TI  - Glutamine: a potentially useful supplement for athletes.
AB  - The role of glutamine as a possible ergogenic aid has not been posited in the
      scientific literature. Although there is an abundance of clinical evidence
      supporting the need for exogenous glutamine in the maintenance of muscle protein
      mass and immune system function in critically ill patients, little work has been
      done that examines the potential utility of glutamine for athletes engaged in
      heavy exercise training. This brief review will describe a number of studies on
      the effects of glutamine supplementation on muscle protein mass, immune system
      function, and glucose regulation. Based on the available clinical evidence, we
      would speculate that glutamine has potential utility as a dietary supplement for
      athletes engaged in heavy exercise training.

PMID- 9916178
TI  - Identifying bottlenecks in endurance performance: the conductance theorem.
AB  - The various transport processes that contribute to human endurance performance,
      such as oxygen intake, elimination of carbon dioxide, lactate and heat, and the
      delivery of metabolic fuels, can all be represented by conductance analogues. The
      use of such models is helpful in identifying bottlenecks within each of these
      systems, and in comparing parallel systems such as the intake of oxygen and the
      elimination of carbon dioxide. However, in order to make the models manageable,
      many simplifications are necessary, and corresponding caution is needed in
      drawing inferences from conductance analogues.

PMID- 9916179
TI  - The gas transporting systems: limits and modifications with age and training.
AB  - The interplay of cardiovascular and cellular oxygen uptake determinants of
      aerobic performance and the system adaptations to training in different
      population samples are examined in order to describe the limitation. With VO2max,
      a central limitation following myocardial infarction and ageing is modified with
      training. Peripheral adaptations occur and stroke volume may be increased
      primarily through improved diastolic filling. In submaximal perturbations,
      control of the increase in O2 uptake at exercise onset (O2 kinetics) is most
      often under peripheral metabolic control, but in exceptions may also be limited
      by central factors. In young and old the peripheral machinery is matched to the
      growth (puberty) and loss (ageing) of muscle mass. Cardiac stroke volume capacity
      may adjust following the changes in muscle mass. Submaximal endurance is closely
      influenced by the anaerobic threshold (theta(an)) and peripheral factors of
      oxidative metabolism. Relative to VO2max, the theta(an) is low in children and
      high in older adults, perhaps reflecting a slow time course in full development
      and loss of peripheral adaptations. Remarkable increases in endurance performance
      are related to relatively small changes in the maximal capacity and the relative
      intensity of performance.

PMID- 9916180
TI  - The effects of endurance training on muscle fibre types and enzyme activities.
AB  - Practitioners and scientists have demonstrated great interest in the
      physiological and biochemical effects of endurance training on the results of the
      marathon run. It is well documented that athletes with a large proportion of slow
      twitch and fast twitch aerobic skeletal muscle fibre, high metabolic enzyme
      activities and concentrations, large mitochondria concentration and, of course,
      the ability to increase the power output generated for a given rate of oxygen
      consumption and energy expenditure, are generally highly successful distance
      runners. Aerobic and endurance training have been shown to bring about
      significant adaptations to the skeletal muscle and its inclusions as well as to
      the delivery system. In particular, enzyme activity levels are readily mutable,
      mitochondrial concentrations increase, and some evidence suggests that the fibre
      distribution is changed. This article briefly reports on changes in skeletal
      muscle brought about by endurance training and those changes that appear most
      effective in yielding success in endurance events.

PMID- 9916181
TI  - Haemoglobin, blood volume, cardiac function, and aerobic power.
AB  - Alterations in [Hb], which are mediated through changes in arterial oxygen
      content, and alterations in BV, which are mediated through changes in cardiac
      output (Q), have a significant effect on both VO2max and aerobic performance. If
      BV is held constant, a decrease in [Hb] (anaemia) causes a decrease in VO2max and
      aerobic performance, while an increase in [Hb] (blood doping) causes an increase
      in VO2max and aerobic performance. If [Hb] is held constant, an increase in BV
      can cause and increase in both VO2max and aerobic performance, while a decrease
      in BV can cause a decrease in VO2max and aerobic performance. In addition, an
      increase in BV can compensate for moderate reductions in [Hb] through increase in
      Q, allowing VO2max to remain unchanged or even increase. Also, a large portion of
      the difference in the enhanced cardiovascular function of endurance athletes is
      due to their high BV and the resultant enhancement of diastolic function. Hence,
      optimizing both [Hb] and BV is a very important consideration for endurance
      performance.

PMID- 9916182
TI  - Markers of excessive exercise.
AB  - Overtraining is of serious concern to long-distance runners and will affect 65%
      of them at some time in their competitive career. The clinical presentation is
      nonspecific but the classical symptoms include fatigue, mood disturbances,
      frequent upper respiratory infections and injury, and a decrease in performance.
      Dysfunction of the hypothalamic pituitary axis from repeated stress, of a
      physical or nonphysical nature, represents the most likely pathogenesis of this
      condition. There is no single biological marker that is diagnostic of an
      overtrained state; however, several parameters deserve further study. The time to
      volitional fatigue on a cycle ergometer at an intensity of 110% of the individual
      anaerobic threshold represents a possible laboratory test. Salivary IgA holds
      promise as a useful immunoligical marker of the overtrained state and further
      research is needed to determine the validity of plasma glutamine as a blood
      marker. The most promising tool at present is a measure of the athlete's mood
      state, and several psychological tools can be used for this purpose.

PMID- 9916183
TI  - Determination of critical power by pulmonary gas exchange.
AB  - Although the physiological underpinnings of critical power (CP) have yet to be
      fully elucidated, it has been proposed that CP demarcates the heavy and severe
      exercise intensity domains and that each domain is associated with a different
      pattern of metabolic response and mechanism of fatigue. Severe intensity has been
      defined such that, during exercise at intensities above CP, the slow component of
      the VO2 response will drive VO2 to VO2max at the point of fatigue. In this study,
      two parameters were derived for each of 8 participants: (a) CP, the asymptote of
      the relationship between power and time to exhaustion, and (b) a related
      parameter; CP', the asymptote of the relationship between power and time to
      VO2max. CP' theoretically represents the threshold intensity above which VO2max
      will be elicited during exercise of sufficient duration. Participants performed
      two exhaustive tests at CP. There were three important findings: First, there was
      a practice effect on time to exhaustion at CP, and times increase 27% in the
      second test. Second, both CP and CP' could be obtained with good precision.
      Third, and most important, CP was equal to CP', thereby providing a physiological
      description of the mathematically derived CP parameter. It was concluded that
      VO2max cannot be elicited at intensities equal to or less than CP.

PMID- 9916184
TI  - Acute and chronic hormonal responses to resistance training designed to promote
      muscle hypertrophy.
AB  - Acute and chronic hormonal responses to resistance training were evaluated in 11
      college men who completed 12 weeks (33 sessions) of high volume resistance
      training. No differences in resting concentrations of growth hormone (GH),
      insulin-like growth factor-I, testosterone, or sex hormone-binding globulin
      occurred from pre- and posttraining in the trained vs. nontrained control group.
      However, cortisol (c) decreased 17% for both groups (p < 0.05). There were no
      differences in exercise-induced responses between Sessions 10 and 20, with all
      hormone concentrations increasing (p < 0.05) from pre- at mid- and post exercise
      session. However, after correction for plasma volume decreases, only C and GH
      showed differences, with C increased from mid- to postsession (48% 10th; 49%
      20th), and GH increased from pre- at mid- and postsession for both sessions 10
      (0.16 +/- 0.42 pre; 4.77 +/- 6.24 mid; 6.26 +/- 5.19 post; microg x L-1) and 20
      (0.33 +/- 0.85 pre; 5.42 +/- 9.08 mid; 8.24 +/- 7.61 post; microg x L-1).
      Significant correlations (p&lt 0.05) existed only between absolute mean GH
      increases from presession and the degree of muscle fiber hypertrophy for type I
      (r = 0.70 mid, 0.74 post) and type II (r = 0.71 post) fibers. In conclusion,
      resistance training had no effect on resting serum hormone concentrations,
      whereas similar acute exercise responses occurred between the 10th and 20th
      training sessions.

PMID- 9916185
TI  - Fractures of the posterior wall of the acetabulum.
AB  - Only 30% of posterior-wall acetabular fractures involve a single large fragment.
      The majority are multifragmentary or have areas of impaction. Unsatisfactory
      clinical results occur in more than 80% of patients treated non-surgically.
      Operative management usually offers the best chance of preserving long-term joint
      function, but only if an anatomically reconstructed acetabulum can be achieved
      without complication. The keys to surgical success include maintaining the
      viability of the fracture fragments and the femoral head itself, using bone
      grafts and buttress plating to support elevated and comminuted fragments, and
      protecting the neurovascular structures at risk. Complications can include
      sciatic nerve injury (incidence, 3% to 18%), heterotopic ossification (7% to
      20%), and osteonecrosis of the femoral head (5% to 8%). Despite the relative
      simplicity of this acetabular fracture, unsatisfactory outcomes after surgical
      repair of the posterior wall occur in at least 18% to 32% of cases, results that
      are worse than for most of the other more complex acetabular fracture patterns.

PMID- 9916186
TI  - Use of reconstruction rings for the management of acetabular bone loss during
      revision hip surgery.
AB  - Aseptic loosening remains the leading cause of failure after total hip
      replacement. Extensive bone loss and acetabular bone stock deficiency are
      frequently encountered. Simple autografting techniques are often not possible,
      and copious amounts of allograft may be required to reconstruct the defect. The
      mechanically stable environment that is a prerequisite for successful graft
      incorporation cannot be achieved with routine acetabular fixation techniques
      alone. A reconstruction ring that is secured to the surrounding pelvis provides a
      more rigid construct. Several types of reconstruction rings are available for the
      management of acetabular bone loss during revision hip surgery. Early results
      suggest that these devices may prove to be a useful alternative for treatment of
      a difficult problem.

PMID- 9916187
TI  - Osteoporosis: current modes of prevention and treatment.
AB  - The most common metabolic bone disorder is osteoporosis, which affects 25 million
      Americans, of whom 80% are women. Bone loss in women occurs most commonly after
      menopause, when the rate of loss may be as high as 2% per year. Bone mass can be
      determined with dual-energy x-ray absorptiometry. The rate of active loss can be
      assayed by the detection of bone collagen breakdown products (e.g., N
      telopeptide, pyridinoline) in the urine. Although it has been suggested that
      white women are most commonly affected, Hispanic and Asian women are also
      affected. Strategies for the prevention and treatment of osteoporosis are
      directed at maximizing peak bone mass by optimizing physiologic intake of
      calcium, vitamin D therapy, exercise, and maintenance of normal menstrual cycles
      from youth through adulthood. Coupled with drug therapy should be a comprehensive
      approach to exercise and fall prevention. Stretching, strengthening, impact, and
      balance exercises are effective. Of the balance exercises, tai chi chuan has
      proved to be the most successful in decreasing falls. Prevention of bone loss is
      obviously preferable to any remedial measures, but new therapeutic strategies
      provide a means of restoring deficient bone.

PMID- 9916188
TI  - Partial-thickness tears of the rotator cuff: evaluation and management.
AB  - The approach to management of a partial-thickness rotator cuff tear is best made
      with the understanding that this is not a singular condition. Rather, partial
      tears represent the common outcome of a variety of insults to the rotator cuff.
      Degenerative changes due to aging, anatomic impingement, and trauma may all be
      etiologic agents. Overhead athletes may develop tears due to repetitive
      microtrauma or internal impingement. Outlet radiographs and magnetic resonance
      imaging are recommended for routine preoperative evaluation. A nonoperative
      treatment program for rotator cuff strengthening and stretching is appropriate as
      initial treatment; modification of activities and anti-inflammatory medication
      are often used as well. Operative management may be considered when nonoperative
      treatment fails. Arthroscopic evaluation is required to determine the true extent
      of the cuff lesion. Arthroscopic subacromial decompression is recommended when
      outlet impingement is present. Rotator cuff debridement or formal cuff repair is
      dependent on the size of the cuff defect and the age and activity level of the
      patient. The importance of recognizing the different causes of partial-thickness
      rotator cuff tears is emphasized in this review of pathogenesis, clinical
      diagnosis, imaging, and treatment.

PMID- 9916189
TI  - Management of neuropathic fractures in the foot and ankle.
AB  - Neuroarthropathy, a rapid, painless destructive process, has become increasingly
      prevalent among long-lived diabetic patients. It is characterized by warm,
      swollen joints with a grossly disorganized radiographic appearance, in spite of
      which the patient is often pain-free. Neglect of this condition results in
      progressive deformity or instability, often complicated by ulceration and
      infection, which can ultimately result in loss of independent mobility, loss of
      the affected limb, and even death. In most cases, a plantigrade, stable, and
      functional foot can be achieved with simple nonoperative techniques, such as the
      use of a total-contact cast or shoe modification. A few patients in whom
      uncontrolled instability or major osseous prominences cause recurrent ulceration
      will require reconstructive surgery (either exostectomy or
      osteotomy/arthrodesis). Although some patients will have an improvement in
      function, ongoing vigilance is necessary.

PMID- 9916190
TI  - Functional fracture bracing.
AB  - Functional bracing is an effective therapeutic modality in the management of
      selected fractures of the tibia, humerus, and ulna, particularly low-energy
      injuries. In the case of tibial fractures, it is applicable only to reduced
      transverse fractures and to axially unstable fractures with an acceptable degree
      of shortening. The rate of union of tibial fractures after functional bracing is
      approximately 97%. The initial shortening noted with closed tibial fractures
      rarely increases with weight bearing. Shortening has been reported to be as
      little as 12 mm in 95% of patients, with angulation of 8 degrees in 90%. Such
      minimal shortening and angulation do not affect functional results. In closed and
      type I open diaphyseal humeral fractures treated with functional braces, the
      nonunion rate is approximately 3%. Most of the reported residual angular
      deformities have been functionally and cosmetically acceptable. For isolated
      ulnar fractures, the nonunion rate is approximately 2%. Functional fracture
      bracing is predicated on the premise that motion at the fracture site encourages
      osteogenesis. The method is applicable only to selected fractures, and it is
      necessary to have a clear understanding of its rationale, indications, and
      technique.

PMID- 9916191
TI  - Pediatric flatfoot: evaluation and management.
AB  - Although the exact incidence of flatfoot in children is unknown, it is a common
      finding. All children have only a minimal arch at birth, and more than 30% of
      neonates have a calcaneovalgus deformity of both feet. This condition is not
      painful and generally resolves without treatment; very rarely is corrective
      casting necessary. Most children who present to an orthopaedist for evaluation of
      flatfoot will have a flexible flatfoot that does not require treatment.
      Nevertheless, the examining physician must rule out other conditions that do
      require treatment, such as congenital vertical talus, tarsal coalition, and skew
      foot. Untreated, congenital vertical talus may result in an awkward gait;
      manipulation and casting have been tried, but most authors now agree that
      surgical treatment is required. Although tarsal coalitions can become
      asymptomatic in adulthood, the anatomy will never be normal. Resection and inter
      position of the extensor digitorum brevis is the treatment of choice for
      calcaneonavicular coalitions; the results of treatment of talocalcaneal
      coalitions are less predictable. Skewfoot should be treated by manipulation and
      serial casting as soon as it is detected. In the older child, hindfoot
      stabilization and realignment of the midfoot may be necessary. Surgical
      management is rarely indicated for a true flexible flatfoot. A variety of tendon
      transfers and reconstructive procedures have been advocated, but none has proved
      uniformly successful. Nor has any of the various types of supports ever been
      shown to change the arch architecture. Although parents are often concerned about
      pediatric flatfoot, the child is usually found to be asymptomatic, and no
      treatment is indicated. In most instances, the best treatment is simply taking
      enough time to convince the family that no treatment is necessary.

PMID- 9916192
TI  - Total antioxidant activity measured by chemiluminescence methods.

PMID- 9916193
TI  - Ferric reducing/antioxidant power assay: direct measure of total antioxidant
      activity of biological fluids and modified version for simultaneous measurement
      of total antioxidant power and ascorbic acid concentration.

PMID- 9916194
TI  - Automated electron spin resonance free radical detector assays for antioxidant
      activity in natural extracts.

PMID- 9916195
TI  - Measurement of oxidizability of blood plasma.

PMID- 9916196
TI  - Measurement of oxygen radical absorbance capacity in biological samples.

PMID- 9916197
TI  - Analysis of ascorbic acid and dehydroascorbic acid in biological samples.

PMID- 9916198
TI  - Analysis of water-soluble antioxidants by high-performance liquid chromatography
      with electrochemical detection.

PMID- 9916199
TI  - Ascorbic acid recycling in rat hepatocytes as measurement of antioxidant
      capacity: decline with age.

PMID- 9916200
TI  - Detecting and measuring bioavailability of phenolics and flavonoids in humans:
      pharmacokinetics of urinary excretion of dietary ferulic acid.

PMID- 9916201
TI  - Antioxidant activity by headspace gas chromatography of volatile oxidation
      products of omega-6 and omega-3 polyunsaturated lipids.

PMID- 9916202
TI  - Determination of oxidized and reduced lipoic acid using high-performance liquid
      chromatography and coulometric detection.

PMID- 9916203
TI  - Flow cytometric determination of cellular thiols.
AB  - Several biochemical techniques are based on chromatography or electrophoresis for
      the determination of thiols from biological samples. These techniques are
      indispensable for the accurate and sensitive detection of specific thiols. Flow
      cytometric determination of cellular thiols is a powerful technique that is
      perhaps best suited for clinical application, particularly for cells in blood or
      other body fluids. Information can be obtained from a small sample amount with a
      relatively little and quick sample treatment. This technique offers an unique
      advantage to study the thiol status of a subset of cells because data are
      collected from individual cells. Multiparameter flow cytometry allows the study
      of different subsets of immunotyped cells. A major drawback of the flow
      cytometric method is the lack of specificity for the determination of distinct
      thiols. The reaction between MBB and thiols is not specific for any particular
      intracellular thiol, although almost all of the entire thiol-reacted bimane
      emission is specific for thiols in general. This limitation can be partly
      overcome by the treatment of cells with known thiol regulatory agents as
      described in the section on the differential assessment of cellular thiols.

PMID- 9916204
TI  - Measurement of glutathione, glutathione disulfide, and other thiols in mammalian
      cell and tissue homogenates using high-performance liquid chromatography
      separation of N-(1-pyrenyl)maleimide derivatives.

PMID- 9916205
TI  - Ratio of reduced to oxidized glutathione as indicator of oxidative stress status
      and DNA damage.

PMID- 9916206
TI  - Nonenzymatic colorimetric assay of glutathione in the presence of other
      mercaptans.

PMID- 9916207
TI  - Protozoological method for assaying lipoate in human biologic fluids and tissue.

PMID- 9916208
TI  - Antioxidant activity of amidothionophosphates.

PMID- 9916209
TI  - Quantitation of anethole dithiolthione using high performance liquid
      chromatography with electrochemical detection.

PMID- 9916210
TI  - Gas chromatography-mass spectrometry analysis of vitamin E and its oxidation
      products.

PMID- 9916211
TI  - Determination of vitamin E forms in tissues and diets by high-performance liquid
      chromatography using normal-phase diol column.

PMID- 9916212
TI  - Sensitive high-performance liquid chromatography techniques for simultaneous
      determination of tocopherols, tocotrienols, ubiquinols, and ubiquinones in
      biological samples.

PMID- 9916213
TI  - High-performance liquid chromatography-coulometric electrochemical detection of
      ubiquinol 10, ubiquinone 10, carotenoids, and tocopherols in neonatal plasma.
AB  - A micromethod for the rapid simultaneous determination of several lipophilic
      antioxidants in plasma from newborn infants is presented. Because only 5
      microliters of plasma is required, the procedure lends itself for repetitive use
      in very immature infants at risk for developing so-called "oxygen radical
      diseases of the premature." The method allows continuous monitoring of
      antioxidants in such patients and can easily be combined with monitoring other
      parameters of interest in this context. Reuse of blood samples taken routinely
      for the determination of hematocrit and bilirubin concentration is possible,
      reducing the blood volume required to be taken for the oxygen radical-related
      studies to virtually zero.

PMID- 9916214
TI  - Simultaneous determination of retinol, tocopherols, carotene, lycopene, and
      xanthophylls in plasma by means of reversed-phase high-performance liquid
      chromatography.

PMID- 9916215
TI  - Assessment of prooxidant activity of vitamin E in human low-density lipoprotein
      and plasma.

PMID- 9916216
TI  - Interactions between vitamin A and vitamin E in liposomes and in biological
      contexts.

PMID- 9916217
TI  - On-line solid-phase extraction and isocratic separation of retinoic acid isomers
      in microbore column switching system.
AB  - On-line solid-phase extraction coupled with micro-HPLC by column switching is an
      ideal technique for the analysis of retinoic acid in serum or plasma. The
      advantages are mainly contributed to an automated sample workup and low detection
      limits. On-line processing of the sample ensures minimal losses and full light
      protection during the entire procedure. Critical steps such as evaporation,
      extraction, and multiple transfers are avoided. Furthermore, the precision of
      highly automated methods is generally better than manual methods. We have
      successfully coupled a 2.1-mm I.D. analytical column with a 2.1-mm extraction
      column. This setup allows for large amounts of supernatant to be injected onto
      precolumns for concentration and cleanup. By means of column switching, this
      concentrate is transferred to the microcolumn with a highly reduced volume. The
      reduced diameter of the analytical column and the on-line solid-phase extraction
      allow for the fully automated quantification of as little as 100 fmol all-trans
      retinoic acid in human serum. The detection limits obtained with these column
      switching techniques can compete with LC-MS. This new micro-HPLC method will be
      useful for the quantitation of endogenous retinoic acid metabolites, which are
      present at very low concentrations in biological material. Furthermore, more
      sensitive methods might also lead to the discovery of hitherto unknown retinoic
      acid metabolites. The combination of on-line SPE and micro-HPLC has, to our
      knowledge, not been used previously for retinoic acid analysis. The development
      of isocratic separation methods for retinoic acid isomers made this possible.

PMID- 9916218
TI  - Purification and characterization of cellular carotenoid-binding protein from
      mammalian liver.
AB  - A cellular carotenoid-binding protein was purified to homogeneity from beta
      carotene-fed ferret liver utilizing the following steps: ammonium sulfate
      precipitation, ion exchange, gel filtration, and affinity chromatography. The
      final purification was 607-fold. beta-[14C]Carotene copurified with the binding
      protein throughout the purification procedures. SDS-PAGE of the purified protein
      showed a single band with an apparent molecular mass of 67 kDa. Scatchard
      analysis of the specific binding of the purified protein to beta-carotene showed
      two classes of binding sites; a high-affinity site with an apparent Kd of 56 x
      10(-9) M and a low-affinity site with a Kd of 32 x 10(-6) M. The Bmax for beta
      carotene binding to the high-affinity site was 1 mol/mol whereas that for the low
      affinity site was 145 mol/mol. The absorption spectrum of the complex showed a 32
      nm bathochromic shift in lambda max with minor peaks at 460 and 516 nm. Except
      for alpha-carotene and cryptoxanthin, none of the model carotenoids or retinol
      competed with beta-carotene binding to the protein. Thus, a specific carotenoid
      binding protein of 67 kDa size has been characterized in mammalian liver with a
      high degree of specificity for binding only carotenoids with at least one
      unsubstituted beta-ionone ring.

PMID- 9916219
TI  - Analysis of zeaxanthin distribution within individual human retinas.

PMID- 9916220
TI  - Optical measurements of calcium signals in mammalian presynaptic terminals.

PMID- 9916222
TI  - Tagging potassium ion channels with green fluorescent protein to study mobility
      and interactions with other proteins.

PMID- 9916221
TI  - Fluorescence techniques for measuring ion channel activity.

PMID- 9916223
TI  - Spin-label electron spin resonance and Fourier transform infrared spectroscopy
      for structural/dynamic measurements on ion channels.

PMID- 9916224
TI  - Nuclear magnetic resonance spectroscopy of peptide ion channel ligands: cloning
      and expression as aid to evaluation of structural and dynamic properties.

PMID- 9916225
TI  - Ligand binding methods for analysis of ion channel structure and function.

PMID- 9916226
TI  - Three-dimensional structure of membrane proteins determined by two-dimensional
      crystallization, electron cryomicroscopy, and image analysis.

PMID- 9916227
TI  - Drug-dependent ion channel gating by application of concentration jumps using U
      tube technique.
AB  - The rapid application system described has been used to study a variety of ionic
      channels in several different types of single cells. The system is inexpensive,
      easy to install, and can be used repeatedly. The consumption of UTS, i.e., drugs
      or agonists, is low. The time interval between switching the valve and the
      expected effect is often shorter than 150 ms for cells about 8-15 microns in
      diameter and is about 20-25 ms for patches positioned in the hole of the U-tube.
      Time and duration of substance application can be controlled by a computer
      connected to a digital-analog (D/A) output.

PMID- 9916228
TI  - Voltage-clamp biosensors for capillary electrophoresis.

PMID- 9916229
TI  - Ion channels as tools to monitor lipid bilayer-membrane protein interactions:
      gramicidin channels as molecular force transducers.

PMID- 9916230
TI  - Purification and reconstitution of epithelial chloride channel cystic fibrosis
      transmembrane conductance regulator.

PMID- 9916231
TI  - Purification, characterization, and reconstitution of cyclic nucleotide-gated
      channels.

PMID- 9916232
TI  - Purification and heterologous expression of inhibitory glycine receptors.

PMID- 9916233
TI  - Purification and functional reconstitution of high-conductance calcium-activated
      potassium channel from smooth muscle.

PMID- 9916234
TI  - Reconstitution of native and cloned channels into planar bilayers.

PMID- 9916235
TI  - Iodide channel of the thyroid: reconstitution of iodide conductance in
      proteoliposomes.

PMID- 9916236
TI  - Nystatin/ergosterol method for reconstituting ion channels into planar lipid
      bilayers.
AB  - The nystatin-ergosterol (N/E) method is described and reviewed. Using this
      procedure, an experimenter can promote and detect fusion of vesicles with planar
      lipid bilayers. N/E fusion provides a straightforward mechanism to reconstitute
      any membrane protein into planar lipid bilayers. Once reconstituted, it is easy
      to determine the ion selectivity, transport rate, voltage dependence, and
      kinetics of any conductance caused by the membrane protein. Fusigenic N/E
      vesicles are made with a mixture of phospholipids, ergosterol, and nystatin.
      Vesicle size can be adjusted either with sonication or with polycarbonate
      filters. The best vesicles contain approximately 20 mol% ergosterol, are
      approximately 200 nm in diameter, and are in a solution containing approximately
      50 micrograms/ml nystatin. Vesicle fusion requires an osmotic gradient and
      delivery of vesicles to the bilayer. Vesicle delivery is increased by (1)
      stirring of the chamber that contains vesicles, (2) larger bilayers, and (3)
      bilayers that are face-flush with the vesicle-containing solution. Because
      constant stirring is critical for delivery of vesicles to the bilayer, a system
      that allows simultaneous stirring and sensitive electrical measurements is
      desirable. The main strength of the bilayer technique has always been that the
      experimenter has control over the milieu of the membrane system. The N/E fusion
      technique adds to this strength by controlling fusion of vesicles to the bilayer,
      thus allowing the quantitative transfer of isolated proteins from vesicle to
      bilayer. The techniques and calculations necessary for successful quantitative
      reconstitution are given in detail.

PMID- 9916237
TI  - Isolation of transport vesicles that deliver ion channels to the cell surface.
AB  - The squid giant axon provides a very simple preparation for the collection of
      bulk quantities of transport vesicles, and this greatly facilitates the
      physiologic study of ion channels incorporated into planar bilayers from these
      vesicles. However, this preparation is also limited in the repertoire of
      transport vesicles that can be studied, and it is not very convenient for some
      biochemical techniques, such as pulse-chase labeling experiments. Cultured N1E
      115 cells, on the other hand, provide a preparation from which a larger
      repertoire of types of transport vesicles can be isolated, and many biochemical
      techniques can be applied in conjunction with physiologic studies. Further
      refinement of the techniques for isolating specific populations of vesicles from
      cultured cells will provide even greater insight into the role of vesicles in
      mediating ion channel trafficking.

PMID- 9916238
TI  - Protein phosphorylation of ligand-gated ion channels.

PMID- 9916239
TI  - Analysis of ion channel associated proteins.

PMID- 9916240
TI  - Signal transduction through ion channels associated with excitatory amino acid
      receptors.

PMID- 9916241
TI  - Secondary messenger regulation of ion channels/plant patch clamping.

PMID- 9916242
TI  - ATP-sensitive potassium channels.

PMID- 9916244
TI  - Simplified fast pressure-clamp technique for studying mechanically gated
      channels.

PMID- 9916243
TI  - Mechanosensitive channels of bacteria.

PMID- 9916245
TI  - Virus ion channels.

PMID- 9916246
TI  - Ion channels in microbes.

PMID- 9916247
TI  - Design and characterization of gramicidin channels.
AB  - This article summarizes methods for the chemical synthesis and biophysical
      characterization of gramicidins with varying sequences and labels. The family of
      gramicidin channels has developed into a powerful model system for understanding
      fundamental properties, interactions, and dynamics of proteins and lipids
      generally, and ion channels specifically, in biological membranes.

PMID- 9916248
TI  - Functional analyses of aquaporin water channel proteins.

PMID- 9916249
TI  - Pore-blocking toxins as probes of voltage-dependent channels.

PMID- 9916250
TI  - Conus peptides as probes for ion channels.

PMID- 9916251
TI  - Scorpion toxins as tools for studying potassium channels.
AB  - The search for peptidyl inhibitors of K+ channels is a very active area of
      investigation. In addition to scorpion venoms, other venom sources have been
      investigated; all of these sources have yielded novel peptides with interesting
      properties. For instance, spider venoms have provided peptides that block other
      families of K+ channels (e.g., Kv2 and Kv4) that act via mechanisms which modify
      the gating properties of these channels. Such inhibitors bind to a receptor on
      the channel that is different from the pore region in which the peptides
      discussed in this chapter bind. In fact, it is possible to have a channel
      occupied simultaneously by both inhibitor types. It is expected that many of the
      methodologies concerning peptidyl inhibitors from scorpion venom, which have been
      developed in the past and outlined above, will be extended to the new families of
      K+ channel blockers currently under development.

PMID- 9916252
TI  - Potassium ion channel inactivation peptides.

PMID- 9916253
TI  - Interactions of snake dendrotoxins with potassium channels.

PMID- 9916255
TI  - Antibodies to ion channels.

PMID- 9916254
TI  - Use of planar lipid bilayer membranes for rapid screening of membrane active
      compounds.

PMID- 9916256
TI  - Internet information on ion channels: issues of access and organization.

PMID- 9916257
TI  - [Effect of cytochrome P450-dependent metabolites of arachidonic acid on the
      functional state of vessels].
AB  - The present paper reviews recent studies about the role of the cytochrome P-450
      dependent arachidonic acid metabolites. There metabolites take part in the
      regulation of the vascular tone. They are the intracellular messenger and play an
      integral role in the relation of the vascular endothelium and smooth muscle
      cells. The arachidonic acid metabolites regulate the activity of the ionic
      channels. It is demonstrated that derivatives of arachidonic acid have the role
      in the pathogenesis of hypertension.

PMID- 9916258
TI  - [The use of alternative sources of electrons in mono-oxygenase reactions
      catalyzed by cytochrome P450. Physico-chemical methods as factors acting on
      enzymatic activity of proteins].
AB  - Influence of physico-chemical methods on catalytic activities of enzymes,
      (cytochrome P450 in particular), has been reviewed. Authors discussed the
      properties of semisynthetic flavohemoproteins based on cytochrome P450. With
      emphasis on recovery of alternative electron sources for redox enzymes. As
      alternative electron sources we have discussed electrochemical methods which
      allow electrons to be used as a reagent for redox system and photoreduction of
      photosensitive molecules. The effects of the chemical modification, high
      pressure, temperature, organic solvents on enzyme activity have also been
      analysed.

PMID- 9916259
TI  - [Designing drugs for transport into the brain].
AB  - This review focused on current of strategies for drug delivery to brain,
      including molecular modification, redox systems and liposomes. Particularly the
      transport through the blood-brain barrier relating to Parkinson's disease are
      being separately considered.

PMID- 9916260
TI  - [Lipid composition of high density lipoproteins in familial
      hyperlipoproteinemias].
AB  - The lipid composition of high density lipoproteins was studied in 53 patients
      with various forms of hereditary hyperlipoproteinemia. 20 healthy individuals
      formed control group. One-dimensional thin-layer chromatography on silica gel
      with two solvent systems was used to separate lipid fractions of high density
      lipoproteins. Ten fractions were identified: four phospholipids
      (phosphatidylcholine, lysophosphatidylcholine, sphingomyelin,
      phosphatidylethanolamine) mono-, di-, and triglycerides, free cholesterol,
      cholesterol esters and free fatty acids. Proportion of HDL phospholipid and
      cholesterol fraction got by Shimadzu (CS-930) chromato-scanner corresponds to
      data received with the use of traditional methods. Comparison of high density
      lipoproteins lipid classes proportions for the individuals with normo- and
      hyperlipoproteinemia demonstrates increase of lysophosphatidylcholine and
      decrease of phoshatidylethanolamine for all hereditary hyperlipoproteinemia forms
      investigated in the study.

PMID- 9916261
TI  - [Brain cerebrosides and sulfocerebrosides after treatment with hydrocortisone].
AB  - The influence of the high dose of hydrocortisone on the content of
      galactocerebrosides, sulfocerebrosides and cholesterol was studied in different
      regions of growing rat brain. The most distinct alterations in content and
      relationship of glycolipids were demonstrated in brain hemisphere and cerebellum.
      The results allow to suggest a conclusion about changes in myelin's lipid
      metabolism and disturbance of myelinogenesis after high dose hydrocortisone
      injection.

PMID- 9916262
TI  - [Modeling of a three-dimensional structure of cytochrome P-450 1A2 and search for
      its new ligands].
AB  - The substances inhibiting cytochrome P450 1A2 (CYP1A2) represent a perspective
      class of new drugs, which application in clinical practice can become the
      important part in preventive maintenance in oncology. The present work is devoted
      to computer modelling of 3-D structure of CYP1A2 and searching of new inhibitors
      by database mining. The modelling of CYP1A2 was done based on homology with 4
      bacterial cytochromes P450 with known 3-D structure. For optimization of CYP1A2
      active site structure the models of its complexes with characteristic substrates
      (caffeine and 7-ethoxyresorufin) were designed. These complexes were optimized by
      molecular dynamics simulation in water. The models of 24 complexes of CYP1A2 with
      known ligands with known Kd were designed by means of DockSearch and LeapFrog
      programs. 3D-QSAR model with good predictive force was created based on these
      complexes. On a final stage the search of knew CYP1A2 ligands in testing database
      (more than 23.000 substances from database Maybridge and 112 known CYP1A2 ligands
      from database Metabolite, MDL) was executed. 680 potential ligands of CYP1A2 with
      Kd values, comparable with known ones were obtained. This number has included 73
      compounds from 112 known ligands, introduced in tested database as the internal
      control.

PMID- 9916264
TI  - [Genotype analysis of biochemical status in people irradiated with significant
      doses of radiation].
AB  - 416 workers of the enterprise of a nuclear industry aged from 52 to 78 years
      exposed to chronic influence of external gamma-irradiation in summary dozes 1.0
      7.56 Gy and plutonium-239 incorporation, (in 32.3% of cases exceeding the
      allowable limit) were studied. A correlation between a complex of 26 biochemical
      and immunochemical parameters and the radiating factors was investigated at
      different haptoglobin genotypes (Hp). It was established, that the greatest
      number of changes of biochemical parameters related to radiating influence, was
      observed at the people with a genotype Hp 2-2 (7 parameters), to a lesser degree-
      at a genotype Hp 2-1 (5 parameters) and in some more smaller degree--at a
      genotype Hp 1-1 (4 parameters). All investigated people with a genotype 2-2 were
      characterised by increase of serum protein entropy.

PMID- 9916263
TI  - [Effect of carnosine and its N-acetyl derivative on the stability of erythrocytes
      in patients with alcoholism during abstinence].
AB  - The effects of carnosine, a natural dipeptide, and its derivative, N- acetyl
      carnosine (Ac-carnosine), on the stability and shape of red blood cells obtained
      from abstinent alcoholics was studied. In the presence of both carnosine and Ac
      carnosine, the erythrocytes of abstinent alcoholics show a statistically
      significant increase in their ability to resist acidic hemolysis. Investigations
      of microscope pictures also show that carnosine and Ac-carnosine have beneficial
      effects on the pathological state of abstinent alcoholic erythrocytes. The
      addition of carnosine and Ac-carnosine resulted in the normalization of cell
      morphology (in 12 and 17 out of 30 cases, respectively). These results may be due
      to the stabilizing and regenerating ability of these compounds on alcoholic
      erythrocytes.

PMID- 9916265
TI  - [Dynamics of lipid peroxidation and antioxidant system in patients with severe
      combined trauma].
AB  - The objective of the study was to determine the influence of blood loss volume on
      lipid peroxidation (LP) process and antioxidant system (AOS) state in the
      patients with a heavy combined trauma. The studies were proceeded in 36 patients
      with a heavy combined trauma. The mean age of the patients was 40 +/- 2. A
      craniocerebral trauma was associated with trauma of both thorax and abdominal
      cavities and locomotor system. Blood loss reached 75% of circulating blood volume
      (CBV), mean value was 28 +/- 3%. Blood samples for the studies were obtained at
      admission of the patients by emergency medical service teams, and--after 4; 24
      hours, 3 and 7 days after the trauma. CBV determination was made by dradioisotope
      method. LP and AOS state was judged from serum level of primary (conjugated
      dienes), secondary (malonic dialdehyde, MDA) LP products and extracellular
      antioxidant enzyme ceruloplasmin (CP). K coefficient, an integral indicator was
      used for LP-AOS system imbalance assessment. According to the obtained data, in
      the studied patients intensification of the LP processes manifesting in CD and
      MDA contents increase was most expressed from 1 to 3 days after trauma (2.0-2.6
      fold, p < 0.05) and rise of TP content maximally in the 3 day 2.28-fold (p <
      0.05) was observed in the there patients. At the admission of decrease (1.6-fold,
      p < 0.05) was registered which normalized to the 3 day. K coefficient time course
      study permitted to establish that as early as at the admission of the patients
      into the clinic its value was substantially higher than the normal one, and to
      the 4 hour the imbalance in the LP-AOS system increased 5.0-fold (p < 0.05). An
      expression of LP processes and AOS disturbances in the patients with heavy
      combined trauma depended on the blood loss volume. The revealed imbalance in the
      LP-AOS system is indicative of a necessity of inclusion antioxidants into the
      complex therapy.

PMID- 9916266
TI  - [Biochemical study of unusual cases of Fabry disease].
AB  - Fourteen members of family P. and four members of family N. were clinico
      biochemically examined. Among twelve adult children (19-32 years old) of family
      P. five sons manifested angiokeratotic skin lesions and other clinical signs of
      Fabry disease. Three of the probands had additional symptoms not generally found
      in Fabry disease. Biochemical studies including an enzyme assay, analysis of
      storage products and alpha-galactosidase multiple forms, allowed us to confirm
      the diagnosis of Fabry disease in four affected brothers and to establish the
      heterozygous status of their mother. The data of biochemical investigation of
      patient N. with atypical variant of Fabry disease are also presented. The patient
      N. with strong skin lesions had a high residual alpha-galactosidase activity and
      unusual composition of alpha-galactosidase multiple forms.

PMID- 9916267
TI  - [Novel approaches to the study of autoregulation of alternative complement
      pathway].
AB  - Experimental and literary data on the peculiarities of complement alternative
      pathway (APC) self-regulation and regulation are reviewed. There is a discussion
      of the methods of APC evaluation, including a new one, called complement
      hemolytical capacity. It is shown that the duration of complement-dependent
      hemolysis lag-period is limited by factor D concentration. The phenomenon of
      acceleration of APC-dependent hemolysis by membranes of lysed cells is described.
      The latter is an evidence of APC functioning in the mode of double amplification.

PMID- 9916268
TI  - [Socioeconomic framework].

PMID- 9916269
TI  - [Political distribution problems of social security].
AB  - The ongoing change of demographic and economic structures does not undermine
      employment (as many believe), but this change indeed induces problems with the
      mandatory old-age security system in Germany. This paper discusses some popular
      reform proposals and concludes with another proposal which takes into account
      economic incentives. Especially the gerontological aim of a longer life-time
      employment is addressed.

PMID- 9916270
TI  - [The future of public health].
AB  - As the results of the structural reform policy regulating the health care sector,
      the paper presents the possible path of increasing intrasectoral risk selection
      and intersectoral risk externalization (especially between the law of health care
      insurance, the law of statutory nursing insurance, and the German poverty law).
      Particularly the new developments in the hospital sector will be analyzed
      regarding the dynamics of risk selection and risk externalization. The new
      economic ways of financing the hospital sector are inducing the need of
      systematic integration of the different branches of social law, especially more
      developed networks of the health care, the nursing system, and the social care
      services.

PMID- 9916271
TI  - [Nursing care in social change. Effects of nursing care insurance on the status
      of the disabled].
AB  - The effects of "Care-insurance" on the situation of those in need of home care,
      is the object of first implementation-studies of SGB XI. They largely agree on
      the high level of satisfaction found among those who draw the benefits of the
      insurance scheme, particularly among those who claim a cash premium; further they
      largely agree on the low level of influence of the "Care-insurance" on changes in
      the form of nursing. An account of the results of the milieu-oriented "Freiburger
      Pflegestudie", which investigates the effects of "Care-insurance" differentiated
      according to the various types of care-situations, forms the centre of the
      article.

PMID- 9916272
TI  - [The local community as a life environment for the elderly--on the future role of
      the community in supporting the elderly].
AB  - This paper is based on the assumption that the community has--by constitutional
      law--an all-embracing responsibility for concerns/matters on the local level. In
      this context, special emphasis is put on the meaning of the local community as
      "social space". From this fundamental understanding, important tasks are derived
      for the community which refer to the needs assessment, planning, and co
      ordination of help and services for older people. Here, this contribution draws
      upon recommendations which were given by the "Deutscher Verein fur offentliche
      und private Fursorge" in Frankfurt/Main at the end of 1997.

PMID- 9916273
TI  - [Future organizational structures for old age homes and nursing homes].
AB  - New organizational concepts are of significant importance for homes for the
      elderly. Restructuring of the homes is necessary because of some fundamental
      weaknesses in the contemporary elderly care system as well as the shift of the
      level of aspiration which is expected by the formation of the so-called "new
      elderly". Main topics in the restructuring process are consumer orientation, core
      organizational competences, and core processes. The challenge for the management
      is not to copy "ideal" models but to develop and to implement new structures
      which fit into the special context of the homes.

PMID- 9916274
TI  - [Nursing home admission for the elderly and chances for avoiding admission.
      Results of a representative study of facilities for inpatient nursing care].
AB  - In this study the rate of institutionalization in old age for the first time is
      analyzed on a retrospective data set: the Altenheimsurvey and the Socio-Economic
      Panel-Survey. The study relies on 5,150 persons aged 60 and over. Based on these
      data, a variety of insufficiently answered questions were analyzed. Among the
      results, (1) the age increase of the institutionalization rate relies only to a
      minor extend on declining health and declining social networks, (2) the higher
      institutionalization rate of women is entirely ascribed to widowhood, and (3) non
      familiar social networks are of minor importance.

PMID- 9916275
TI  - [Workload and stress in caring for the elderly: status of research and research
      agenda].
AB  - Providing adequate care of the aged, geriatric caregivers take a key position for
      the transfer of gerontological knowledge into practice. However, little attention
      has been focussed on the work conditions and staff distress by gerontologists.
      The purpose of this paper is to review studies on occupational stress relating to
      professional geriatric caregivers. Based on relevant research concepts and
      paradigms, findings of the international literature are summarized. The review
      shows that occupational stress is affected by a number of work-related factors
      from behavior problems of the residents to time pressure and organizational
      deficits. The stress in turn can cause burnout, mental health problems, somatic
      complaints, and increased turnover. Social support and control at the workplace
      are supposed to contribute essentially to stress reduction. There are few
      empirical studies dealing with occupational stress among geriatric caregivers in
      Germany. Strengths and weaknesses of the studies will be analyzed and suggestions
      offered for future research in this area. Extending research is needed
      particularly on the work conditions in the increasing field of geriatric
      outpatient community services. Inspite of its theoretical and methodological
      shortcomings, the findings highlight the need for strategies to prevent physical
      and mental health problems, burnout, and job turnover. It is a challenge for
      gerontological research to obtain more knowledge on the work-related factors
      leading to stress as well as to establish effective intervention strategies to
      reduce its long-term consequences.

PMID- 9916276
TI  - [Patient management in geriatric psychiatry by ambulatory care services. Results
      of an empirical analysis].
AB  - This study was designed to provide information to which extend home-based nursing
      care services for the elderly take part in the care for older people with mental
      disorders. Also of interest was the involvement of clinical facilities and
      services of the geropsychiatric treatment system in the health care for the
      clients. A one day data collection in 29 nursing care services in two North Rhine
      Westphalian regions could raise informations about 1,246 clients aged 60 years
      and over 1,522 persons (41.8%) had a mental disorder, diagnosed by a nursing
      and/or medical professional. 68% of the mental disordered clients had dementia or
      a demential disorder, 6% a functional psychosis, and 31% a neurotic, psychogenic
      disorder or substance abuse (small number of clients with two and more
      diagnoses). 82% of clients with mental disorders had one or more additional
      somatic disease(s). These diseases were mostly the cause for the involvement of
      home-based nursing care service. Barely 8% of clients with mental disorders were
      placed from clinical facilities and services of the geropsychiatric treatment
      system into the nursing care services. Beside the home-based care, only a 12% of
      mental disordered received clients outpatient psychiatric treatment. Systematic
      cooperation between the nursing care services and the system of (gero-)
      psychiatric treatment was a rare exception.

PMID- 9916277
TI  - [Institutional care for frail elderly from Weimar to Bonn (1924-1961)].
AB  - The article deals with the development of institutionalized care and its overall
      discourse concerning the elderly sick people in Germany from 1924 to 1961. This
      period of time embraces an ambivalent process of modernization that falls short
      of any unilinear success story. Neither politics nor the medical sciences had the
      impact to make the nursing homes catch up with the advanced hospitals. They
      became low-grade institutions within the national welfare system. These homes
      evolved from poor-law houses with no specialized care whatsoever. The chronically
      ill and infirm old people emerged during the 19th century not as the result of
      straight forward professionalization. The Social Hygiene in the Weimar period and
      the racist paradigm of the Nazi-period turned a blind eye to the chronically ill
      elderly people well into the era of the murderous "euthanasia". At least in the
      second half of World War II chronically sick old people were increasingly
      regarded as so called "useless eaters" and, thus, doomed to be killed or starved
      to death. The mortality rate remained very high after the end of the war due to
      wide-spread hunger. The situation did not improve until 1948 and in the 50s this
      part of state welfare took advantage of the general expansion in the social and
      health care system.

PMID- 9916278
TI  - [Nutritional status of participants in the Giessen Senior Long-Term Study with
      respect to antioxidant vitamins and selenium].
AB  - Within the longitudinal study on nutrition and health status in an aging
      population of Giessen, Germany, baseline measurements with regard to antioxidant
      status were obtained in 85 free living elderly persons. The subjects were at
      least 60 years old, non-smoking, feeding themselves, and not supplementing any
      vitamins or minerals. Dietary intake of nutrients was assessed by means of a 3
      day estimated food record, which was especially developed and validated for this
      study. Antioxidant status was evaluated by fasting plasma concentrations of
      vitamin C, E, beta-carotene, and selenium. The results show that in this study
      group self-determined nutrition provides enough nutrients to yield a good
      antioxidant status in the advanced age. Although no differences could be detected
      in dietary intake of vitamin C, E, and beta-carotene between males and females,
      significantly higher plasma concentrations of all substances investigated were
      found in females when compared to males.

PMID- 9916279
TI  - [Analysis of claims for damage in the gynaecological sector during 1997 based on
      data taken from the Professional Association of Gynaecologists' third-party
      liability group insurance].
AB  - This survey deals with claims for damages in the gynaecological sector during
      1997 brought against gynaecologists covered under the professional association's
      third-party liability group insurance. These claims are typified and presented
      according to the tenor of the substantiations. The analysis shows that only in
      the case of a small percentage of the claims was incorrect treatment conclusively
      the cause of damage,thus resulting in prompt settlement. With regard to the other
      claims, the status of each dispute is listed as of June 30, 1998. In view of the
      difficulty that patients have in proving incorrect treatment and resultant damage
      (the burden of evidence lying with the patient), the focus of such disputes
      regularly shifts to allegations of inadequate prior information, since the
      physician has to prove due provision of the same, and to the assertion that
      documentation was incomplete, since deficient documentation can act in favour of
      the patient by alleviating the onus of furnishing proof, even to the extent of
      transferring such onus to the other party. Consequently, liability risk can be
      reduced by conscientious provision of prior explanatory information and precise
      documentation of this information and of the treatment.

PMID- 9916280
TI  - [Quality assurance under professional law and law relating to health services
      physicians and doctors].
AB  - Medical quality assurance is guaranteed by a partially supplementary and
      partially contradictory systemframework of professional provisions as well as the
      provisions that apply to health service physicians. As far as qualifications are
      concerned, quality assurance is primarily the responsibility of the medical
      boards. Competing provisions are to be found particularly in the area of process
      quality. With a view to co-ordinating them, the Work Group for the Promotion of
      Quality Assurance in Medicine has been set up, sponsored by the Federal Medical
      Board, the Federal Association of National Health Service Physicians, the German
      Hospital Organisation and the leading statutory health insurance associations.
      The role of the Federal Medical Board in the field of quality assurance has been
      considerably upgraded pursuant to the Second Reform Index [II. NOG]. The article
      refers to several quality assurance projects, exploring in depth, for example,
      quality assurance in the areas of blood group identification and blood
      transfusion.

PMID- 9916281
TI  - [Quality assurance based on civil and penal law].
AB  - The term "quality assurance" primarily concerns the provisions of professional
      regulations and law relating to health service physicians. It would be too
      sweeping to regard liability or criminal law as normative parameters for
      guaranteeing quality assurance in the narrower sense. Nevertheless, along with
      expert opinions sought within the context of relevant lawsuits, court rulings
      under civil law and criminal law in effect constitute an indirect form of
      "quality control". As a consequence, many court decisions act as a standard for
      the future. Civil law is concerned with determining whether the patient has
      received the quality of medical service to which he is entitled; for all intents
      and purposes, the same applies to the judgement of medical treatment under
      criminal law, whereby all cases, whether civil or criminal, concern diagnostic
      and therapeutic practice in specific treatment situations, the organisation of
      treatment and the provision of information. With regard to these areas, a
      contribution can therefore be made to quality assurance by observing pertinent
      civil and criminal judicature.

PMID- 9916282
TI  - [Quality assurance by experts].
AB  - The predominance of medical experts in hearings on so-called professional
      malpractice has frequently been bemoaned, but is indispensable since lawyers lack
      the necessary knowledge and requisite expertise. Court decisions are therefore
      essentially dependent on the quality of expert medical opinions, which in turn
      are dependent on the professional competence of the expert and on whether the
      expert is aware of the judicial demands made of him, i.e. whether the expert
      correctly understands his status and function within the scope of the civil or
      criminal proceedings. For example,the fact that court practice allows for
      differing standards (i.e. that medical standards can vary within limits) is
      important for the expert's appraisal, as is also knowing to what extent he is
      bound by the assignment and which requirements apply for proving causality (i.e.
      of an error leading up to damage) in civil and criminal proceedings. Strict
      objectivity, comprehensible language, restriction to one's own special field,
      preparation of the report within a reasonable time, intellectual integrity, no
      dealing with legal issues, ex ante assessment of the case and personal
      responsibility for the opinion are other important precepts that must be adhered
      to in order to avoid a miscarriage of justice. Quality control as exercised by
      specialised experts is therefore of vital significance.

PMID- 9916283
TI  - [Quality assurance and risk management in gynecology and obstetrics].
AB  - A glance through the relevant supreme court cases of the last five years will
      conclusively reveal that obstetrics is currently the sector with the largest
      number of liability claims, despite the fact that German obstetrics hold a
      leading world position. This high risk entails high insurance premiums, which can
      threaten the existence of those exercising the profession and which can therefore
      not be increased indefinitely. Thus the causes of these exploding liability
      claims in the medical sector have to be combated, i.e. the origins of damage have
      to be tracked down in order to identify and eliminate or at least reduce the
      risks. This future-oriented approach of damage prevention is known as risk
      management, and entails almost complete elimination not so much of maltreatment
      but most certainly of deficiencies in information, organisation and documentation
      as well as equipment. Seen from this point of view, risk management represents a
      form of quality control based on relevant judicature and statutory provisions.
      American experience shows that risk management activities are indispensable
      today, and that only proactive and preventive risk control, as opposed to limited
      reactive risk control, is capable of stemming the flood of liability claims in
      the medical sector.

PMID- 9916284
TI  - [Termination of pregnancy on embryopathic grounds--means to medical decision
      making].
AB  - Now that german legislators have dispensed with explicit formulation of an
      embryopathic indication, such cases are covered by the unlimited medical
      indication as defined under Sec. 218a para, 2 of the German Criminal Code.
      Determining such an indication "in accordance with medical findings" presents the
      physician with an extremely difficult diagnostic task. Since basic social
      consensus does not exist with regard to the content of decisions based on
      embryopathic grounds, quality assurance measures can only target the decision
      making process. The central means that the physician has of determining the
      extent of the related conflict consists of discussion with the patient of her
      assessment of the situation. Seen in this context, abolition of the patient's
      obligation to seek counselling in such cases, as arising in connection with
      relinquishment of explicit formulation of the embryopathic indication,
      constitutes an incorrect legislational decision that contradicts the entire
      concept of the law. On the physician's part, this can be countered by
      guaranteeing that the patient is provided with comprehensive medical information
      and encouraging her to partake of in social counselling.

PMID- 9916285
TI  - Investigation into the efficacy of disinfectants against MRSA and vancomycin
      resistant enterococci.
AB  - In the study reported here, several disinfectants for surfaces, instruments,
      hands and mucous membrane were tested for their effectiveness against methicillin
      resistant strains of S. aureus and vancomycin-resistant enterococci. The results
      show that after use of the recommended concentrations with the recommended
      contact times, which were determined on the basis of the criteria for
      disinfectants according to the DGHM guideline for the testing and evaluation of
      chemical disinfection procedures, an adequate effect was able to be proved.
      Increased resistance of the methicillin-resistant S. aureus and vancomycin
      resistant E. faecium strains to the tested disinfectants was not found. Only
      after use of diluted solutions differences in the bacterial count reductions were
      observed. In further studies it is to be investigated whether these differences
      are due to resistance to antibiotics or to intrinsic resistance.

PMID- 9916286
TI  - Model tests for the efficacy of disinfectants on surfaces. IV. Communication:
      dependence of test results on the amount of contamination and the kind of active
      substance.
AB  - In the assessment of efficacy of surface disinfectants, many influencing factors
      have to be taken into account. One essential item is whether the surface to be
      disinfected is clean or soiled. Among the feasible soilings, the blood is of
      particular consequences because it ads impediments to many disinfecting agents.
      This paper shows to what extent the impairment of the efficacy of typical active
      agents depends on the blood burden of the surfaces. Therefore, test surfaces
      (varnished plywood) were contaminated with 0.01 to 0.08 ml of coagulating blood
      per test area (3 cm2). The blood contained cells of Staphylococcus aureus as test
      germs. The disinfection was effected by immersing the test objects in the
      disinfecting solution for 5 seconds and mingling the adhering disinfecting
      solution (about 0.02 ml) with the coagulated blood on the test surface with a
      glass spatula for about 20 seconds. Subsequently, the test objects remained in a
      horizontal position at room conditions for 4 hours and then the numbers of
      surviving test germs were determined. The graphical representation of the results
      shows that the efficacy curves of formaldehyde and phenol lie very closely
      together, i.e. their effect is hardly impaired by the different blood burdens of
      the test areas. The efficacy curves of glutaraldehyde, peracetic acid, chloramine
      T, and quaternary ammonium compounds lie very far apart from each other. To
      achieve the same microbicidal effect (log N/N0 = -5) when the contaminating
      amount is raised from 10 microliters/3 cm2 to 80 microliters/3 cm2, the
      concentration of chloramine T has to be raised by a factor of 5.4, peracetic acid
      by a factor of 9, glutaraldehyde by a factor of 24, quaternary ammonium compound
      even by a factor of 67. Ethanol and sodium hypochlorite showed a divergent
      behaviour. For ethanol, the efficacy diminution produced by increasing the
      contamination amount by a factor of 4 can be compensated by raising the
      concentration from 50% to about 70%. But again and again, there were test objects
      on which the number of germs able to reproduce had only been lowered by a factor
      of about 10(-3). At the highest contamination of 80 microliters/3 cm2, even 95%
      ethanol proved to be completely insufficient. With sodium hypochlorite even at
      the lowest contamination of 10 microliters/3 cm2, a microbicidal effect of only
      about 10(-5) was obtained. With increasing contamination, the highest achievable
      microbicidal effect clearly decreased. It is remarkable that the microbicidal
      effect of this active agent decreased with increasing concentrations. The results
      show how important it is in testing the efficacy of disinfecting agents to
      exactly lay down the amount of contaminating substances. To find out how safely
      an agent works under harder circumstances, the dependence of the microbicidal
      effect from the amount of contaminating substances per test area has to be
      determined.

PMID- 9916287
TI  - Which conditions promote a remanent (persistent) bactericidal activity of
      chlorine covers?
AB  - The interaction of disinfectants containing active chlorine compounds
      (hypochlorite, chloramine T) with skin surfaces produces a so called chlorine
      cover which is a true chemical transformation of the protein matrix of the
      outermost horny skin layer by forming covalent N-Cl bonds. Though its intensity
      can easily be measured, the results on its remanent (persistent) bactericidal
      action until now have not been described consistently. While Gottardi and Karl
      observed a well-defined remanent action which correlated with the cover strength
      in the artificially with E. coli contaminated arm, Koller, Rotter, and Gottardi
      were not able to prove it, neither in artificially contaminated hands nor in the
      case of the resident bacterial colonization. To clarify these not consistent
      results, the bactericidal activity of chlorine covers on transient (dry
      contamination of the finger tips with Micrococcus luteus) as well as on resident
      colonization (after wearing gloves for 3 h) has been re-investigated using
      contact plates for recovering the bacteria. The results are showing that the
      remanent bactericidal action of chlorine covers strongly depends on the skin
      milieu, with moist conditions caused by sweat (surgical gloves) favoring the
      bactericidal activity. Elution experiments prove that protein constituents
      (detected by UV-spectrometry) continuously are transported to the skin-surface.
      It is obvious that the latter equilibrate with the chlorine cover by forming
      bactericidal N-Cl compounds with the effect that oxidation capacity fixed at the
      protein matrix is mobilized enabling the remanent bactericidal action.

PMID- 9916288
TI  - [Effect of steam application based on microbiological and parasitologic test
      procedures].
AB  - In the present study steam application was investigated with regard to
      microbicidal and parasiticidal effects. The cleaning apparatus used (Uninova
      Company) works at a boiler pressure of about 5 bar and consequently with a
      temperature up to 155 degrees C inside the boiler. Whereas the ambient atmosphere
      working temperature of steam is slightly below 100 degrees C. The tests are based
      on the DVG guidelines for testing chemical disinfectants (2). Different steaming
      times and distances were used in germ carrier tests with three different germ
      carriers (tile, wood, carpet) and three different test germs (Staphyloccocus
      aureus, Pseudomonas aeruginosa, Candida albicans) in order to determine the
      optimum conditions for biocidal effects of steam-application. These optimum
      conditions were additionally tested with two test viruses (ECBO- and Reo-virus)
      and a parasitological resting form (ascarid worm eggs). Swirling of germs caused
      by steam turbulence was minimized by covering the steam outlet nozzle with cloth.
      The experiments showed logarithmical reduction factors of at least 5.0 in the
      germ count at steaming times of 5 seconds and a steaming distance of 2.5 cm for
      all three test germs on all three germ carriers (mean of 10 repeated tests). The
      virological tests showed good disinfection results after a steaming time of only
      2 seconds using aseptic gauze as germ carrier and also after 5 seconds using wood
      as a carrier. Finally in testing vitality of undeveloped Ascarid worm eggs only 2
      seconds of steam treatment proved to be sufficient for a 100 percent destruction.
      According to the present results steam treatment is most likely to become a
      valuable, ecologically compatible method in controlling hygienic problems, with a
      potential of partly replacing chemical disinfectants. In particular we see
      applications in keeping pets and companion animals, provided the above mentioned
      rules are followed (steaming distance 2.5 cm; steaming time 5 seconds; cloth). In
      farm animal stables steam disinfection seems harder to achieve because of large,
      rough surfaces and economical reasons as e.g. expenditure of time and energy.

PMID- 9916289
TI  - Detection of Pseudomonas aeruginosa in bronchial and tracheal aspirates by PCR by
      amplification of the exotoxin A gene.
AB  - For the first time, a PCR test based on the amplification of the Exotoxin A was
      evaluated for its ability to rapidly detect Pseudomonas aeruginosa in tracheal
      and bronchial aspirates from mechanically ventilated patients. The reaction is
      based on the amplification of a 396 bp region within the Exotoxin A gene. The
      results show that this PCR-method is suitable for the detection of Pseudomonas
      aeruginosa even in clinical samples such as aspirates. Among the 380 clinical
      samples tested in this way, 57 were found to be positive while only 36 were
      positive using routine culture. In conclusion, these results suggest that the PCR
      method mentioned above can be used to provide a specific, rapid, simple, and
      highly sensitive detection of Pseudomonas aeruginosa in clinical samples.

PMID- 9916290
TI  - [Comparison of four methods for the detection of fecal streptococci in water].
AB  - The objective of this study was to select an effective and fast method for the
      detection of socalled fecal streptococci in water by comparing a method according
      to the German drinking water standard, a membrane filtration method according to
      the ISO-draft standard 7899/2, the Chromocult Enterococcus Broth (Merck) and the
      Enterolert-System (IDEXX). The study was based on a collective of 297 water
      samples derived from different stages of water treatment and distribution, as
      well as from individual water supplies. The sensitivity, reliability, and
      selectivity of the single methods in relation to their practicability was
      evaluated. Concerning false positive and false negative results, the tests were
      proved by metabolic characterization of the isolated strains. The advantages and
      disadvantages of the methods resulting from the investigated criteria are
      discussed. The work is part of a comparative study within the scope of the DIN ad
      hoc-committee "fecal streptococci".

PMID- 9916291
TI  - Detection of Budvicia aquatica and Pragia fontium and occurrence in surface
      waters.
AB  - We have reported a method for quantitative detection of Budvicia aquatica and
      Pragia fontium from water samples. Budvicia aquatica but not Pragia fontium was
      detected in the investigated surface water and sewage water samples.

PMID- 9916292
TI  - [Emissions from building products and investigation of their toxicity with the
      bioluminescence inhibition test].
AB  - The investigation of building products in test chambers contains so far only
      analytical and sensory measurements. In this paper, first experiments for the
      direct testing of the acute toxicity of building product emissions with the
      bioluminescence inhibition test are presented. The test specimen was a solvent
      free dispersion paste for gluing carpets. Two tests with different air change
      rates were performed in a 1 m3 stainless steel test chamber. The emissions were
      concentrated at uniform timesteps in impinger-bottles and measured with the
      bioluminescence inhibition test. At the same time the concentrations of the
      emissions in the test chamber were measured both with charcoal adsorbent tubes
      (carbon disulphide desorption) and with tenax tubes (thermal desorption). The
      results of the bioluminescence inhibition test show, that the decrease of the
      toxicity over a period of 28 days is far lower at a low air change rate than at a
      higher air change rate. We also found, that from the multitude of the emitted
      substances the toxicity for the luminescence bacteria was only caused by Ethanol
      [2-(2-butoxyethoxy)]-acetate.

PMID- 9916294
TI  - [Occupational exposure to inhalation anesthetics at the work-place of veterinary
      surgery].
AB  - In a prospective study we evaluated the work-place pollution by isoflurane and
      nitrous oxide during various anaesthetic procedures in animal surgery. The study
      was conducted during one working week at an University Animal Department. Trace
      concentrations of isoflurane and nitrous oxide were directly measured every
      minute in the breathing zone by means of a photoacoustic infrared spectrometer in
      two different operating rooms (OR) with an air turnover of 17 changes per hour.
      In one OR the 8-hour time-weighted average (mean +/- SEM) was calculated to be
      12.3 +/- 9.9 ppm nitrous oxide and 1.9 +/- 2.5 ppm isoflurane. The other OR,
      where only isoflurane was used, was contaminated with 5.3 +/- 8.1 ppm isoflurane.
      In the first OR, the trace gas concentrations were low and comparable to values
      obtained under human anaesthesia in adults and children. The higher contamination
      in the second OR resulted from performing inhalational anaesthesia with an open
      mask system in birds and small animals. Although the mean values were below the
      recommended occupational exposure standards, some high peak values (> 300 ppm
      isoflurane) violated these threshold limits. We recommend the use of a local
      scavenging device, if other alternatives such as total intravenous anaesthesia
      are not possible.

PMID- 9916293
TI  - [Emissions and immisions of bio-aerosols from a duck fattening unit].
AB  - In a field study emissions and immissions (receptor exposition) of bioaerosols
      emitted from and near a duck fattening house (25 m distance) were investigated.
      Within the livestock building mean concentrations of 3,342,289 CFU m-3 for
      airborne total mesophilic bacteria were determined. Total dust and endotoxin
      yields were 1.9 mg m-3 and 7,132.4 ng m-3, respectively. Additionally,
      enterobacteria, mesophilic and thermotolerante fungi as well as mesophilic
      actinomycetes were detectable. Measurements of immissions have shown, that
      downwind in the rear of the house a mean total germ concentration of 10,007 CFU m
      3 was measurable in contrast to the upwind side of the building, where no
      airborne mesophilic bacteria were found. Higher concentrations downwind were
      generally determined for total dust, mesophilic fungi and actinomycetes, too, but
      not so for endotoxins. A supporting application of a numeric dispersion model
      confirmed the immissions for total mesophilic bacteria near by the duck fattening
      house. From this viewpoint immission predictions can be made in future for
      varying input data, i.e. wind conditions, of different components of bioaerosols.

PMID- 9916295
TI  - Mercury concentrations in fetuses with malformations.
AB  - The total mercury concentrations in placenta, kidney and liver of 59 fetuses with
      malformations were detected and measured by cold-vapour atomic absorption
      spectrometry. Median values were 13 micrograms/kg for placenta, 20 micrograms/kg
      for kidney and 31 micrograms/kg for liver, based on the use of paraffin-embedded
      tissue (pt), which generally leads to values of concentration double those
      obtained on a wet weight basis. The tissue concentrations presented here are in
      the same range as results from other studies. Measurements in a control group of
      56 fetuses without malformations from the same geographical region were also
      carried out. These demonstrated a median value of the liver-Hg-burden of 27
      micrograms/kg (pt). The higher liver concentrations of the fetuses with
      malformations could be explained by growth retardation, leading to seemingly
      higher tissue concentrations of mercury. Regarding the results according to the
      organs affected by malformations, no abnormally high Hg-concentrations in the
      liver of any group were detected. Summing up, our investigations show no evidence
      of mercury implication in these malformations, and it was finally concluded that
      the mercury burden of the population in this region would not lead to organ
      malformations in the developing fetus.

PMID- 9916296
TI  - Aeromonas hydrophila associated with a severe outbreak of infection in farmed
      rabbits.
AB  - An outbreak of infection with a high rate of mortality has been detected in an
      industrial rabbitry in Spain. Aeromonas hydrophila was isolated in pure culture
      from liver, lung, heart and spleen of ill and moribund animals. All the isolates
      belonged to O:11 serogroup, autogglutinated after boiling, were resistant to the
      bactericidal action of the fresh rabbit serum and did not agglutinate in
      acriflavine. They were producers of hemolysins and proteases but were not
      enterotoxigenic.

PMID- 9916297
TI  - Inactivation of Salmonella during microwave cooking.
AB  - Sixty meat loaves were experimentally infected with a strain of Salmonella
      serovar mbandaka to give approximately 10(7) cells/g. Thirty contaminated loaves
      were cooked in a microwave oven for 4 min, and 30 other samples for 3 min 30 s,
      both followed by a standing time of 2 min. No viable experimental contaminants
      were recovered from both core and surface samples of the 30 loaves cooked for 4
      min. Loaves cooked for the short time were often Salmonella positive. These
      results point out that infection hazard linked to microwave cooked food can be
      avoided by following adequate procedures concerning exposure time, temperature
      and post-heating holding time. A standardization of microwave ovens for domestic
      use is desirable, making it easier to give users correct instructions based on
      careful and strict experimentations approved by Public Health Authorities.

PMID- 9916298
TI  - Educational status and resources for child care as predictors of TBE vaccination
      coverage in schoolchildren of an endemic area in Austria.
AB  - Since the introduction of the Austrian tick-borne encephalitis (TBE) vaccination
      program in 1981 vaccination coverage of children has not been investigated
      sufficiently. Numerous socioeconomic and demographic factors have been identified
      as being associated with low vaccination coverage in childhood for most
      vaccinations. This study focuses on parental educational status and on resources
      for child care as determinants of tick-borne encephalitis (TBE) vaccination
      coverage of schoolchildren in an endemic TBE area of Austria. The target
      population were children in the first, fourth and seventh year of school
      education in Styria, Austria. Therefore, the sample consisting of 2470 children
      was divided into three age groups, children aged 7, 10 and 13 years. We performed
      a representative cross-sectional study. The information concerning the
      vaccination status of each child was recorded by means of an anonymous
      questionnaire given to the parents by the classroom teachers. This procedure
      ensured a high overall response rate of 79.8%. The prevalence of at least one TBE
      vaccination was 93.9% for the 7 year old, 97.8% for the 10 and 97.9% for the 13
      year old. The lowest vaccination rates were found in families with four or more
      children (94.0%) and for those children who had unemployed parents (92.9%). The
      multivariate analysis indicates that TBE vaccination coverage is affected by a
      large number of children in the family (p = 0.0003), an urban place of residence
      (p = 0.0001) and by a low level of education of the mother (p = 0.013). The
      results suggest that, though overall high coverage in schoolchildren, vaccination
      programmes should be focused on large and socially deprived families.

PMID- 9916299
TI  - Investigation of stereoselective metabolism of amphetamine in rat liver
      microsomes by microdialysis and liquid chromatography with precolumn chiral
      derivatization.
AB  - The utility of microdialysis as a quantitative sampling technique for in vitro
      drug metabolism studies was demonstrated by investigating the stereoselective
      metabolism of D-, L- and DL-amphetamine by the cytochrome P-450 enzymes.
      Microdialysates containing the isomers of amphetamine and its metabolite were
      derivatized with the fluorescent chiral derivatizing agent, (-)-fluorenylethyl
      chloroformate. The diastereoisomers were isocratically separated by liquid
      chromatography (LC) on a reversed-phase C18, 3-micron (100 x 3.2 mm) column. The
      intra- and inter-assay relative standard deviation (R.S.D.) was below 10%.
      Michaelis-Menten parameters, K(m) and Vmax were obtained for the formation of
      both D- and L-hydroxyamphetamine from D-, L- and DL-amphetamine in the
      concentration range of 10-350 microM.

PMID- 9916300
TI  - Gradient elution electrochromatography with a flow-injection analysis interface.
AB  - A flow-injection analysis-capillary electrochromatography interface is used for
      gradient elution capillary electrochromatography giving purely electroosmotic
      flow through the analytical column. Solvent gradients were generated with a micro
      LC system connected to the interface. Injections were carried out on-line using
      an inert rotary LC valve controlled by an electric actuator. Gradient shape was
      measured from acetonitrile (5% acetone)-water (50:50, v/v) to (100:0) in open
      tubular experiments. When compared to conventional instrumentation, peak tailing
      and peak width increased slightly using the interface. A test mixture of nine
      solutes was evaluated in isocratic and gradient elution modes. Using the
      interface, a gradient of MeCN-water (60:40) to (90:10) provided baseline
      separation of all nine solutes in under 18 min with good band spacing.
      Reproducibility of retention times in eight replicate injections was found to be
      better than 2% R.S.D. for all solutes. This interface also allows use of
      autoinjectors and dramatically lessens movement of the packed column, improving
      column lifetime.

PMID- 9916301
TI  - On-line deconjugation of chloramphenicol-beta-D-glucuronide on an immobilized
      beta-glucuronidase column. Application to the direct analysis of urine samples.
AB  - An immobilized HPLC column has been developed for the on-line deconjugation of
      beta-glucuronides. The enzymatic activity of this column has been previously
      demonstrated [1]. This study reports on the application of the immobilized beta
      glucuronidase column to the analysis of glucuronide metabolites in the urine. The
      system utilized in this work was composed of an internal-surface reversed-phase
      (ISRP) column (50 x 4.6 mm) containing a hydrophobic inner phase and a
      hydrophilic outer phase, a beta-glucuronidase immobilized enzyme reactor (BG
      IMER) column (50 x 4.6 mm) and a C8 reversed-phase column (150 x 4.6 mm). The
      columns were connected with three six-port switching valves. A coupled-column
      procedure was developed for urine samples containing chloramphenicol-beta-D
      glucuronides (0.07-1.1 mM/injection). Urine samples were injected into the ISRP
      column where the glucuronides were separated from the biological matrix, with
      matrix contaminants eluting off-line to waste. Eluent from the ISRP column
      containing the glucuronides was then transferred on-line to the beta
      glucuronidase column for deconjugation and passed directly on-line to the C8
      column. In this portion of the chromatographic procedure, the mobile phase
      consisted of 0.01 M ammonium acetate at pH 6.7. The analyte concentrated on the
      top of the reversed-phase column was then eluted using a gradient mobile phase
      system of acetonitrile and 0.01 M ammonium acetate (pH 5.0) and detected at UV
      wavelength of 280 nm.

PMID- 9916302
TI  - Column switching in high-performance liquid chromatography with tandem mass
      spectrometric detection for high-throughput preclinical pharmacokinetic studies.
AB  - A high-throughput liquid chromatography-tandem mass spectrometry method is
      described for the determination of multiple compounds in dog and rat plasma.
      After acetonitrile precipitation of plasma proteins, the analytes are pre
      concentrated and back-flushed on a reversed-phase column for separation using a
      switching valve. The analytes are ionized using TurboIon Spray in a positive
      mode, and detected by multiple reaction monitoring. Automatic tuning software is
      used for fast method development. The data processing is greatly speeded up by
      using a powerful quantitation software package. Chromatography of multiple
      compounds takes only 4 min. The linear calibration curve ranges from 0.5 to 1000
      ng/ml. This method was successfully used in the analysis of multi-compounds for
      preclinical pharmacokinetic studies.

PMID- 9916303
TI  - Improved enantioselective method for the determination of the enantiomers of
      reboxetine in plasma by solid-phase extraction, chiral derivatization, and column
      switching high-performance liquid chromatography with fluorescence detection.
AB  - A rapid enantioselective method is described for the quantitation of the
      reboxetine (R,R)- and (S,S)-enantiomers in plasma utilizing solid-phase
      extraction, derivatization, normal-phase high-performance liquid chromatography,
      and fluorescence detection. Plasma samples (0.1 ml) with added internal standard
      were applied to activated solid-phase extraction discs containing a
      nonpolar/strong cation mixed-phase, washed, eluted, evaporated to dryness, and
      derivatized for 5 min with (+)-1-(9-fluorenyl)ethyl chloroformate. After
      termination of the derivatization reaction, the samples were analyzed by
      isocratic normal-phase HPLC using a silica column and ethanol-heptane (1:124,
      v/v) as mobile phase. The derivatized reboxetine peak was column-switched onto
      cyano and Chiralcel OD-H columns in series using ethanol-heptane (1:49, v/v) as
      mobile phase to resolve the diastereomeric derivatives of the enantiomers and
      separate interferences. The column effluent was monitored with fluorescence
      detection at 260/315 nm. The range of quantitation of each enantiomer was 2-2000
      ng/ml. One sample was injected every 18 min.

PMID- 9916304
TI  - Effect of temperature on retention of enantiomers of beta-methyl amino acids on a
      teicoplanin chiral stationary phase.
AB  - The isocratic retention of enantiomers of beta-methyl amino acids (beta
      methyltyrosine, beta-methylphenylalanine, beta-methyl-tryptophan and beta-methyl
      1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) was studied on a teicoplanin
      containing chiral stationary phase at different temperatures and at different
      mobile phase compositions, using the reversed-phase mode. With variation of both
      mobile phase composition and temperature, almost baseline separations could be
      achieved for all four enantiomers of sterically hindered amino acids. The
      retention factors and selectivity factors for the enantiomers of all investigated
      compounds decreased with increasing temperature. The natural logarithms of the
      retention factors (ln k) of the investigated compounds depended linearly on the
      inverse of temperature (1/T). van 't Hoff plots afforded thermodynamic
      parameters, such as the apparent change in enthalpy (delta H degree), the
      apparent change in entropy (delta S degree) and the apparent change in Gibbs free
      energy (delta G degree) for the transfer of analyte from the mobile to the
      stationary phase. The thermodynamic constants (delta H degree, delta S degree and
      delta G degree) were calculated in order to promote an understanding of the
      thermodynamic driving forces for retention in this chromatographic system.

PMID- 9916305
TI  - Determination of the absolute configuration of alpha-hydroxyglycine derivatives
      by enzymatic conversion and chiral high-performance liquid chromatography.
AB  - We describe an approach for facile determination of the absolute configuration of
      enantiomerically chromatographed racemates by combining enzymatic conversion and
      chiral chromatography. The method involves initial rapid development of chiral
      HPLC methods using polar organic eluents with polysaccharide chiral phases. We
      present here evidence for using the stereospecific peptidylamidoglycolate lyase
      (PGL, E.C. 4.3.2.5) to determine the absolute configuration of alpha
      hydroxyglycine derivatives. The racemic solute was incubated with PGL,
      lyophilized and then enantiomerically chromatographed using the CHIRALPAK AD
      column. Based on the specificity of the enzyme reaction, the unreacted enantiomer
      was assigned the absolute configuration R.

PMID- 9916306
TI  - Optimisation and routine use of generic ultra-high flow-rate liquid
      chromatography with mass spectrometric detection for the direct on-line analysis
      of pharmaceuticals in plasma.
AB  - The use of ultra-high flow-rate chromatography coupled to mass spectrometry
      offers great potential for the rapid, on-line analysis of pharmaceutical
      compounds in plasma as it permits high throughput direct analysis of plasma
      samples without any time-consuming sample preparation such as solid-phase
      extraction. The coupling of mass spectrometry with high-performance liquid
      chromatography often results in enhanced selectivity and sensitivity compared to,
      for example, ultraviolet absorbance detection. This can remove the need for
      complete resolution of the analyte from endogenous materials in the matrix. The
      use of large particle size stationary phases, and therefore, the ability to use
      large porosity column end frits, coupled with the added selectivity and
      sensitivity of the mass spectrometer allows an on-line analysis approach to be
      used for the direct analysis of pharmaceuticals in biological matrices with
      extremely high throughput. This paper presents an overview of the manner in which
      we have optimised this technique for the analysis of plasma samples, in terms of
      gradient profile, system configuration and optimal injection volume for maximum
      throughput and robustness. The nature of the mobile phase flow is also discussed.

PMID- 9916307
TI  - Column switching in capillary liquid chromatography-tandem mass spectrometry for
      the quantitation of pg/ml concentrations of the free basic drug tolterodine and
      its active 5-hydroxymethyl metabolite in microliter volumes of plasma.
AB  - A capillary column switching system was developed for the determination of low,
      unbound concentrations of the basic drug tolterodine and its active 5
      hydroxymethyl (5-HM) metabolite in human plasma. Free concentrations of
      tolterodine and 5-HM at pM and nM (pg/ml and ng/ml) levels were obtained by
      ultrafiltration of 40-400 microliters plasma at 37 degrees C. The free fraction
      (%) was independent of the plasma concentrations of the analytes. Detection of
      the analytes was performed by sheathless electrospray tandem mass spectrometry in
      the multiple-reaction monitoring mode. The selectivity of the mass spectrometric
      detection and the additional clean-up on the pre-column allowed direct injection
      of the ultrafiltrated plasma samples. Tolterodine and 5-HM were pre-concentrated
      on a reversed-phase capillary pre-column (1 cm x 200 microns) and subsequently
      backflushed onto the separation column (25 cm x 200 microns). The stability of
      the chromatographic system was good; a large number of ultrafiltrated plasma
      samples could be injected and the relative standard deviation of the retention
      times was typically < or = 1% (within-day). The accuracy was between 86 and 105%
      and the precision was between 1 and 7% without the use of an internal standard.
      Linear calibration curves were obtained between 100 pM and 100 nM.

PMID- 9916308
TI  - Determination of fluspirilene in human plasma by liquid chromatography-tandem
      mass spectrometry with electrospray ionisation.
AB  - An ultra-sensitive method for the determination of fluspirilene in plasma was
      established, using high-performance liquid chromatographic separation with tandem
      mass spectrometric detection. The samples were extracted with hexane/isoamyl
      alcohol, separated on a Phenomenex Luna C18 5 mu 150 x 2.1 mm column with a
      mobile phase consisting of methanol-water-acetic acid (600:400:1) at a flow-rate
      of 0.3 ml/min. Detection was achieved by a Finnigan Matt mass spectrometer (LCQ)
      at unit resolution in full scan mode scanning the product ion spectrum from m/z
      130-500 and monitoring the transition of the protonated molecular ion at m/z
      476.2, to the sum of the largest product ions m/z 371, 342 and 274 (MS-MS).
      Electrospray ionisation was used for ion production. The mean recovery for
      fluspirilene was 90% with a lower limit of quantification of 21.50 pg/ml using 1
      ml plasma for extraction. This is the first chromatographic method described for
      the determination of fluspirilene in plasma that is accurate and sensitive enough
      to be used in pharmacokinetic studies.

PMID- 9916309
TI  - Simultaneous determination of omeprazole and 5'-hydroxyomeprazole in human plasma
      by liquid chromatography-tandem mass spectrometry.
AB  - A method for the simultaneous determination of omeprazole and 5'
      hydroxyomeprazole in human plasma is described. Isolation of the analytes from
      plasma was achieved via solid-phase extraction using a polymeric sorbent based
      cartridge. The analytes were chromatographed under reversed-phase conditions on a
      Zorbax XDB-C8 column (50 x 4.6 mm). The HPLC mobile phase consisted of a mixture
      of acetonitrile-water (21:79, v/v) containing 10 mM ammonium hydroxide. The
      apparent pH of the mobile phase was adjusted to 8.5 with formic acid prior to
      use. A Sciex API III+ tandem mass spectrometer equipped with a heated nebulizer
      atmospheric pressure chemical ionization interface was used as a detector and was
      operated in the positive ion mode. Multiple reaction monitoring using the
      precursor-->product ion combinations of m/z 362-->214, 346-->198 and 316-->147
      was used to detect 5'-hydroxyomeprazole, omeprazole and internal standard,
      respectively. The method was validated in the concentration range of 10-500 ng/ml
      plasma with adequate assay precision and accuracy. The assay was used to
      determine the cytochrome P450 2C19 phenotype of subjects participating in
      clinical trials of compounds under development.

PMID- 9916310
TI  - Validated high-performance liquid chromatographic methods for quantitation of a
      novel nonsteroidal antiestrogen.
AB  - HPLC assays were developed and validated for the quantitation of the novel orally
      active nonsteroidal antiestrogen EM-800 ?(S)-(+)-4-[7-(2,2-dimethyl-l-oxopropoxy)
      4-methyl-2-[4-[2-(1-pipe ridinyl)- ethoxy]phenyl]-2H-l-benzopyran-3-yl]-phenyl
      2,2-dimethylpropanoate?. The assay involves reversed-phase C18 or C4 columns
      using different mobile phases with ammonium acetate buffers and UV detection at
      lambda = 240 nm. The standard curve was linear over the concentration range of 10
      1100 micrograms/ml. The precision (% relative standard deviation) values of these
      methods were in the range of 0.38-0.52 and 1.89-3.45% with C4 and C18 reversed
      phases, respectively. The limit of detection was found to be 1 microgram/ml.
      Enantiomeric separation was also obtained using a chiral method (ChiralPak AD
      column) using a mixture of hexane-reagent alcohol-diethylamine (94.9:5.0:0.1) as
      mobile phase. These methods were applied to stability studies, evaluation of
      pharmaceutical dosage forms and in the framework of toxicological studies.
      Details of some of these applications will be presented.

PMID- 9916311
TI  - Sensitive determination of a new antiarrhythmic agent, trecetilide, in plasma by
      high-performance liquid chromatography with fluorescence detection.
AB  - Two high-performance liquid chromatography (HPLC) methods were developed for the
      determination of trecetilide in plasma samples. Differing only in the addition of
      a derivatization step and different detection wavelengths, the two methods
      encompassed a wide concentration range. In both methods, plasma samples (0.1 ml)
      with added internal standard were applied to solid-phase extraction discs
      containing a non-polar/strong cation mixed-phase, washed and eluted with an
      acetone-acetonitrile triethylamine mixture. The eluate was evaporated to dryness,
      and either reconstituted and directly injected onto an HPLC column or first
      derivatized with 1-naphthyl isocyanate before HPLC analysis. In both methods, the
      separation was performed isocratically on a cyano analytical column utilizing a
      mobile phase composed of acetonitrile-pH 7.9 phosphate buffer (70:30, v/v). The
      column effluent was monitored by fluorescence detection at 290/345 nm (with
      derivatization) or 235/320 nm (without derivatization). The limits of detection
      and quantitation of the assay were 0.57 and 1.9 ng/ml, respectively, when
      derivatization was used, or 4.3 and 14 ng/ml, respectively, without
      derivatization.

PMID- 9916312
TI  - Straightforward solid-phase extraction method for the determination of verapamil
      and its metabolite in plasma in a 96-well extraction plate.
AB  - Straightforward solid-phase extraction (SPE) methods were developed for the
      determination of verapamil and its metabolite in a plasma matrix. The spiked
      plasma sample was pretreated with 2% phosphoric acid followed by two different
      SPE methods using a Waters Oasis HLB 96-well extraction plate. Recoveries greater
      than 90% were obtained using both a generic and a selective SPE methods. The
      generic method is a good starting protocol, and it is applicable to a wide range
      of compounds. This generic method consists of using 5% methanol as the wash
      solvent, and 100% methanol for the elution. The limitation of the non-specific
      method is that it does not remove all plasma constituents that interfere with the
      quantitation of the metabolite, norverapamil. A second, more specific method was
      developed using the same Oasis HLB sorbent which removes more plasma
      interferences and provides cleaner extracts for the HPLC-UV analysis. This
      selective method uses both the methanol concentration and the pH advantageously
      to preferentially isolate the analytes of interest from a complex sample matrix.
      Recoveries of greater than 90% with R.S.D.s less than 3.8% were obtained with
      this selective method.

PMID- 9916313
TI  - Isocratic, simultaneous reversed-phase high-performance liquid chromatographic
      estimation of six drugs for combined hypertension therapy.
AB  - We report an isocratic, HPLC procedure for assay of the orally administered
      hypertension drugs [atenolol, amlodipine, nifedipine, nitrendipine, nimodipine
      and felodipine given in retention order] of which atenolol, an
      aryloxypropanolamine beta-blocker is administered with anyone of the other five
      dihydropyridine calcium channel blockers in combined hypertension therapy. The
      drugs were dissolved in methanol and 20 microliters of a mix of the drugs was
      injected onto a reverse phase JASCO-metaphase ODS (250 x 4.0 mm) 5 mu column. Any
      one of the six drugs could be used as the internal standard. The drugs were
      resolved by elution with a pH 4.5 equivolume mobile phase of acetonitrile-0.01 M
      KH2PO4, with pH adjustments done with H3PO4 (flow-rate 1.5 ml min-1). The column
      effluent was monitored at 250 nm. The detector response (peak height ratio) was
      linear in the dynamic range of 25-3200 ng ml-1 of these drugs, with the detection
      limits at approximately 15 ng ml-1. Full statistical evaluation of the data
      including linear regression (least-square fit) analysis was performed. The
      suggested procedure has the advantage that all the five dihydropyridine
      derivatives can be quantified alone or in formulation with atenolol.

PMID- 9916314
TI  - Estimation of chlorzoxazone hydroxylase activity in liver microsomes and of the
      plasma pharmacokinetics of chlorzoxazone by the same high-performance liquid
      chromatographic method.
AB  - We have developed a HPLC method which allows the determination of chlorzoxazone
      and its hydroxy metabolite in rat liver microsomes and in human plasma. We found
      that dehalogenated chlorzoxazone or 2-benzoxazolinone was a convenient and stable
      internal standard. Proteins were precipitated with diluted perchloric acid and
      the supernatant was extracted with ethyl acetate. Complete resolution of the
      peaks was achieved within 20 min with a Spherisorb ODS-1 column. The inter-day
      R.S.D.s were 6.5% at 0.5 microgram/ml of hydroxychlorzoxazone and 5.8% at 1
      microgram/ml of chlorzoxazone in human plasma. The reproducibility of the method
      has been demonstrated for a large number of samples over a long period.

PMID- 9916315
TI  - Analysis of nucleotides by capillary electrophoresis.
AB  - Capillary electrophoresis is a useful tool for the analysis of nucleotides.
      Methods have been optimized for both CZE and MECC modes. A variety of CZE
      buffers, such as borate, carbonate and phosphate were used successfully. The pH
      of the buffer changes the charge on the nucleotides. Therefore, the selectivity
      of the analytes can be controlled by the acidity of the buffer solution. CE
      separations of nucleotides have been performed at all pH levels, in both CZE and
      MECC modes. SDS was the most commonly used modifier in MECC separations, but
      other additives have been added to optimize selectivity. In addition, nucleotides
      have been quantified in different matrices, including tissue and cell extracts
      and several DNA and RNA sources. This paper summarizes the methods used for the
      optimization of nucleotides by CE and includes the most recent techniques to
      improve selectivity, reproducibility and sensitivity. A summary of CE methods is
      used in analyses of nucleotides in biological matrices is included.

PMID- 9916316
TI  - Protein-protein interactions on weak-cation-exchange sorbent surfaces during
      chromatographic separations.
AB  - This paper examines the nature of chromatographic separations on a weak cation
      exchange material in which immobilized protein coats 24% or less of the sorbent
      surface. It was found that columns on which proteins were immobilized still
      behaved as a cation-exchange chromatography sorbents, but their selectivity was
      different from the parent weak cation-exchange column. This was interpreted to
      mean that in addition to the normal electrostatic interactions expected in ion-
      exchange chromatography, protein analytes interact with immobilized protein on
      the sorbent surface. Anionic proteins were not adsorbed, indicating that
      immobilized proteins were acting synergistically with ionic stationary phase
      groups to enhance retention. It is concluded that these protein-protein
      interactions occur after proteins are captured by the primary interaction
      mechanism of the column, in this case, electrostatic interaction. Protein-protein
      interaction is a secondary, lateral process. These lateral interactions were
      observed between 4% and 24% surface saturation. The significance of this
      observation is that in preparative chromatography and the case of "fouled"
      columns, strongly adsorbed proteins could alter the elution characteristics of
      sample proteins being target for analysis or purification.

PMID- 9916317
TI  - Protein variant separations by cation-exchange chromatography on tentacle-type
      polymeric stationary phases.
AB  - We developed a set of prototype cation-exchange column packings that are based on
      a hydrophilic coated, pellicular polymeric support with a grafted tentacular
      surface chemistry that is highly suited to resolving closely related protein
      variants. These column packings (1) afford minimal band spreading in conjunction
      with extremely high selectivity, (2) exhibit a very hydrophilic character and (3)
      have moderate loading capacity. Cytochrome c variants (bovine, horse, rabbit)
      were baseline-separated, as was native ribonuclease A and its two deamidation
      products, the Asp67 and isoAsp67 forms. Humanized monoclonal antibody variants
      differing in the presence of lysine at the C terminus of the heavy chains were
      baseline-resolved. Finally, the separation of hemoglobin variants found in a
      sample containing elevated levels of glycated hemoglobin was also demonstrated.

PMID- 9916318
TI  - Purification of TaqI endonuclease from Thermus aquaticus.
AB  - A purification procedure for the thermostable restriction enzyme TaqI was
      developed using high-performance ion-exchange liquid chromatography. The effects
      of various operating conditions on the separation behaviour of TaqI endonuclease
      from the cell extracts were investigated for optimisation and scaling up. The
      separation of the enzyme by HPLC was found to be strongly dependent on the sample
      volume, slope of linear gradient and order of the ion-exchange columns. The final
      yield of the enzyme is also dependent to a great extent upon the number of
      fractionation steps employed to purify the enzyme. In the present study, 4000 U
      TaqI endonuclease per mg protein was recovered from 2 g Thermus aquaticus cells
      with a two-step purification protocol in one day. The purification factor was 24.
      Compared to other classical methods of purification reported in literature with
      4000 or 32,000 U enzyme from 200 g of Thermus aquaticus cells, HPLC yielded
      190,000 U enzyme from 200 g cells using cation and anion HPLC columns
      sequentially and thus resulted in a higher efficiency.

PMID- 9916319
TI  - Determination of submicromolar concentrations of neurotransmitter amino acids by
      fluorescence detection using a modification of the 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate method for amino acid analysis.
AB  - A sensitive method for quantitatively determining submicromolar levels of
      neurotransmitter amino acids (e.g. Asp, Glu and gamma-aminobutyric acid) in
      microdialysates from brain and cerebrospinal fluids is reported. 6-Aminoquinolyl
      N-hydroxy-succinimidyl carbamate (AQC) was employed as the derivatization
      reagent, followed by HPLC separation and fluorescence detection of the
      derivatives. The derivatization was conducted simply by mixing the AQC directly
      with the microdialysis samples. The reaction was complete within seconds after
      mixing at room temperature. Separation development optimizing the gradient
      profile, eluent pH and column temperature resulted in an excellent separation of
      the required amino acids in less than 30 min. Other resolved amino acids in the
      same profile include Gly, taurine, and Pro. Recoveries for the amino acids of
      interest spiked into high salt containing perfusion buffers were greater than
      97%. The sensitivity of the method was increased by employing a 16-microliter
      flow cell in the detector and analyzing 20-microliter aliquots of the
      derivatization mixtures. With the optimized conditions, the detection limits were
      3-7 nM (fmol/microliter). Typical reproducibility (%R.S.D.) for quantitation of
      these amino acids at submicromolar levels was approximately 2%. Excellent
      linearity (r2 > 0.999) was achieved over the range 0.2-20 microM. The low
      detection limits permitted the analysis of a number of different microdialysate
      samples including those from cerebrospinal fluid, as well as substantia nigra and
      hypothalamus from brain samples, even at basal levels where gamma-aminobutyric
      acid concentration may be < 50 nM. The excellent sensitivity made it easy to
      distinguish basal from stimulated levels of neurotransmitter amino acids, even
      from sample sizes as small as 10 microliters.

PMID- 9916320
TI  - High-performance liquid chromatographic determination of total plasma
      homocysteine with or without internal standards.
AB  - Hyperhomocysteinemia is an independent risk factor for atherosclerosis and
      vascular occlusive disease. Assessment of total plasma concentration of
      homocysteine (tHcys) requires accurate and reproducible measurements. The aim of
      this study was to test a rapid isocratic HPLC method for tHcys analysis with an
      internal standard (I.S.) of alpha-mercaptopropionylglycine (MPG), 2
      mercaptoethylamine (ME), or N-acetylcysteine (NAC) or without I.S., and to verify
      whether the use of an I.S. improves the precision. The method without I.S. showed
      an excellent linearity (y = 1.59x - 0.15, r = 1), recovery (100%) and a within
      assay relative standard deviation (R.S.D.) of 1.2%. Instead, in our hands, the
      presence of I.S.s decreased the reproducibility (within-assay R.S.D. ranged from
      4.5 to 6.5%) and lengthened the chromatogram by up to four to five times. In
      conclusion, HPLC measurement of plasma tHcys without I.S. improves accuracy with
      respect to determination with I.S.; moreover, this approach allows to routinely
      process larger amounts of plasma samples.

PMID- 9916321
TI  - Determination of plasma and serum homocysteine by high-performance liquid
      chromatography with fluorescence detection.
AB  - Determination of homocysteine in plasma or serum is becoming an important
      diagnostic procedure. Accurate, rapid and low cost methods for measuring
      homocysteine are therefore required. We have improved an HPLC method and made it
      suitable for clinical application. The total homocysteine in plasma consists of
      free homocysteine (i.e., reduced plus oxidized homocysteine in the non-protein
      fraction of plasma) and protein-bound homocysteine. The method consists of the
      following steps: reduction of the sample with tri-n-butylphosphine, precipitation
      of proteins with trichloroacetic acid (10%) and derivatization with ammonium 7
      fluorobenzo-2-oxa-1,3-diazole-4-sulfonate. The derivatives are separated by
      reversed-phase high-performance liquid chromatography followed by fluorescence
      detection. The concentrations (mean +/- S.D.) of total homocysteine in plasma
      from 77 normal subjects, 44 male and 33 female adults, were 8.4 +/- 2.15 and 7.1
      +/- 1.18 mumol/l, respectively. Serum concentrations were 8.8 +/- 2.6 mumol/l in
      males and 7.6 +/- 1.5 mumol/l in females.

PMID- 9916322
TI  - Liquid chromatography of aromatic amines with photochemical derivatization and
      tris(bipyridine)ruthenium(III) chemiluminescence detection.
AB  - We have shown by flow injection that tris(bipyridyl)ruthenium(III) [Ru(bpy)3(3+)]
      chemiluminescence (CL) detection of some aromatic amines can be enhanced by on
      line photochemical derivatization. Two of the aromatic amino acids, tryptophan,
      and tyrosine as well as the peptide phenylalanine-alanine and other primary
      aromatic amines such as L-dopa, phentermine, and tryptamine upon irradiation with
      UV light are found to give an increased CL signal on the order of 4-9 times that
      for nonirradiated compounds. For benzylamine, phenethylamine, and phenylalanine,
      the improved CL detectability upon photolysis is about 15-16 times better.
      Chemiluminescence detection limits of the photolyzed compounds are generally 2-20
      pmol, significantly better than those by UV-Vis detection at 254 nm. GC-MS work
      has been done to identify the products of some of the photolysis reactions and
      explain the enhanced CL detectability. The fact that other aromatic amines
      without a one or two carbon spacer from the aromatic ring to the amine group such
      as aniline, m- and p-phenylenediamine, and N,N'-dimethylaniline did not show any
      CL signal improvement upon irradiation with UV light suggests that there is some
      selectivity in the reaction. CL detection of aromatic amino acids after on-line
      photochemical derivatization and HPLC has been shown.

PMID- 9916323
TI  - Stability and determination of aflatoxins by high-performance liquid
      chromatography with amperometric detection.
AB  - A method based on reversed-phase high-performance liquid chromatography (RP-HPLC)
      with amperometric detection with a glassy carbon electrode at a constant
      potential of 1.4 V is reported for the separation and identification of
      aflatoxins B1, B2, G1 and G2 in a model mixture. The chromatography was performed
      on a PAH-Baker column with a ternary mobile phase containing methanol,
      acetonitrile and aqueous LiClO4 electrolyte. Aflatoxin G1 showed the highest
      electroactivity in the compound series studied. Calibration curves of aflatoxins
      G1 and B2 were linear up to 0.2 and 0.3 mmol/l, respectively. Sensitivity varied
      between 7 and 10 ng for the different aflatoxins. The combination of different
      HPLC detectors in the analysis of these compounds was applied to investigate the
      stability of aflatoxins G1 and B2.

PMID- 9916324
TI  - Quantitative determination of endogenous retinoids in mouse embryos by high
      performance liquid chromatography with on-line solid-phase extraction, column
      switching and electrochemical detection.
AB  - An isocratic high-performance liquid chromatographic method for the determination
      of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid and all
      trans-retinol in mouse embryos using on-line solid-phase extraction and column
      switching in combination with electrochemical detection has been developed. The
      method was validated using retinoids in albumin solutions and 13-cis-acitretin
      was used as internal standard. About 370 microliters of albumin solution was
      injected on a 10 x 2.1-mm I.D. pre-column packed with Bondapak C18, 37-53-micron
      particles. The proteins were washed to waste within 5 min using as mobile phase,
      a 1:3 dilution of mobile phase 2, which consisted of acetonitrile-methanol-2%
      ammonium acetate-glacial acetic acid (79:2:16:3, v/v). Components retained on the
      pre-column were back-flushed to and separated on the 250 x 4.6-mm I.D. Suplex pKb
      100 analytical column using mobile phase 2. The retinoids were detected
      electrochemically at +750 mV using a coulometric electrochemical detector. The
      total analysis time was about 20 min. Recoveries were in the range of 86-103%.
      The mass limits of detection were about 10 pg and 25 pg for the retinoic acids
      and all-trans-retinol, respectively. The intra-assay precision, reported as
      relative standard deviation, was in general better than 4% (n = 6) for the four
      retinoids. Inter-assay precision was in the range 3-4% (n = 10). The method was
      applied for determination of endogenous retinoids in 9.5 day-old mouse embryos. A
      340-microliter solution containing 100 microliters of embryo homogenate (1.64
      embryos) was analyzed. The concentrations of all-trans-retinol and all-trans
      retinoic acid were found to be 279 pg per embryo and 75.8 pg per embryo,
      respectively. The amount of 13-cis-retinoic acid and 9-cis-retinoic acid was
      below the detection limit.

PMID- 9916325
TI  - Capillary electrochromatography of biomolecules with on-line electrospray
      ionization and time-of-flight mass spectrometry.
AB  - Capillary electrochromatography (CEC) is considered a hybrid of liquid
      chromatography and capillary electrophoresis. It is expected to combine the high
      peak efficiency of capillary zone electrophoresis with the versatility and
      loading capacity of HPLC to bring about another high-performance MS-compatible
      chromatographic system. This paper explores the potential of CEC coupled with the
      electrospray ionization and time-of-flight mass spectrometry in biochemical
      analysis. The packed columns used in this study were tapered at the outlet to
      retain the packing material, thereby obviating the need for an outlet frit.
      Electrosmotically driven solvent gradients were employed for the separation of
      phenylthiohydantoin (PTH)-amino acids by reversed-phase chromatography, and a
      time-of-flight (TOF) mass spectrometer was employed as the detector for the CEC
      column effluent. The effect of CEC operating parameters, such as gradient shape,
      column length, and electric field, on the analytical results from the separation
      and MS detection of a standard mixture of PTH-amino acids was investigated.
      Particular attention was paid to the effect of sheath flow-rate, sheath
      composition and mass spectra acquisition rate on the performance of the
      electrospray TOF-MS.

PMID- 9916326
TI  - Real-time detection of allele-specific polymerase chain reaction products by
      automated ultra-thin-layer agarose gel electrophoresis.
AB  - Ultra-thin-layer agarose gel electrophoresis, a novel combination of agarose slab
      gel electrophoresis and capillary gel electrophoresis was introduced in
      conjunction with laser-induced fluorescence (LIF) scanning detection for the
      analysis of polymerase chain reaction (PCR) products. Allele-specific fragments,
      amplified from genomic DNA of patients with congenital adrenal hyperplasia (most
      often caused by mutations of 21-hydroxylase gene, CYP-21), were used as a model
      system to investigate the applicability, sensitivity and resolving power of the
      method. The allele-specific products were generated by PCR and separated by ultra
      thin-layer agarose gel electrophoresis. The double-stranded DNA fragments were
      easily visualized in real-time via complexation during the separation process by
      the intercalator dye TO-PRO-3 which was part of the separation gel-buffer system.
      In this way, the migrating dsDNA-dye complexes were detected in real-time by a
      scanning LIF detection system with sub-nanogram sensitivity. The system employs a
      632-nm solid-state laser and an avalanche photodiode detector scanning to the
      separation platform by means of a fiber bundle system. Automated ultra-thin-layer
      agarose gel electrophoresis with 'on the fly' TO-PRO-3 staining of dsDNA
      fragments and LIF detection system proved to be a very fast, high-throughput
      separation method for individual or multiplexed PCR products, with excellent
      sensitivity.

PMID- 9916327
TI  - Artificial neural network classification based on capillary electrophoresis of
      urinary nucleosides for the clinical diagnosis of tumors.
AB  - Nucleosides in human urine have been studied frequently as a possible biomedical
      marker for cancers, acquired immune deficiency syndrome (AIDS) and the whole-body
      turnover of RNAs. A capillary electrophoretic method that can quantitatively
      analyze urinary normal and modified nucleosides in less than 40 min with a good
      resolution and sufficient sensitivity has been developed. Twelve kinds of normal
      and modified nucleosides were determined in urine samples from 25 healthy persons
      and 25 cancer patients of 14 kinds of cancers. Artificial neural networks have
      been used as a powerful pattern recognition tool to distinguish cancer patients
      from healthy persons. The recognition rate for the training set reached to 100%
      and above 85% of the members in the predicting set were correctly classified. In
      addition, the neural network technique was compared with methods of the principal
      component analysis and the canonical discriminant analysis. The results
      demonstrate that the predictive ability of the artificial neural network is
      stronger than the others in this study.

PMID- 9916328
TI  - Use of reversed polarity and a pressure gradient in the analysis of disaccharide
      composition of heparin by capillary electrophoresis.
AB  - A capillary electrophoresis method with reversed polarity, combining both the
      application of a voltage and a pressure gradient between the buffer vials, was
      developed for the analysis of eight heparin-derived delta-disaccharides obtained
      by enzymatic depolymerization. A 60 mM formic acid buffer at pH 3.40 was selected
      as running electrolyte, with an applied voltage of -15 kV and an over-imposed
      pressure gradient (3.45.10(-3) MPa) for 6 min from inlet to outlet starting at 20
      min. Figures of merit such as run-to-run and day-to-day precision, and limits of
      detection were established. The electrophoretic method was applied to the
      analysis of depolymerization products of different kinds of heparins. The
      composition of the depolymerization buffer was selected in order to reduce
      baseline distortions in the electrophoretic separation, thus a buffer solution
      containing 20 mM Tris, 50 mM sodium chloride, and 3 mM calcium chloride at pH
      7.10 was used. Percentages of molar disaccharide compositions for unfractionated
      heparins from porcine, bovine and ovine intestinal mucosa, and bovine lung were
      determined. In addition, low-molecular-mass heparins from bovine and porcine
      intestinal mucosa were analysed as well.

PMID- 9916329
TI  - Analysis of biopolymers by size-exclusion chromatography-mass spectrometry.

PMID- 9916330
TI  - Trends in early research careers of life scientists.

PMID- 9916331
TI  - [Initial and continuous education. Entreaty for better education of physicians in
      therapeutics].
AB  - Concrete education on therapeutical decision must constitute a major
      institutional objective during the higher academic period of the medical
      students. The current therapeutics constitutes a branch of instruction based on
      the up-to-date of the "medical science" and on the evidence evaluation. However,
      such evidence-based medicine still biased, evolutionary and thus provisory valid;
      whereas at the same time it must be appropriate and suitable for the patients
      benefit. Data issued from medical science are on the basis of the interactive and
      pragmatic apprenticeship of the therapeutical decision and prescription with a
      personalized approach of patient and at each step of its disease. The continuous
      postgraduate education programs following the initial Academic instruction
      contributes to up date the knowledges and moreover the professional experience
      and practice. This evolution is performed with respect of both the individual
      ethic-related to the patient and the collective ethics in terms of public health.

PMID- 9916332
TI  - [French system of drug surveillance].
AB  - The French drug surveillance system is characterized by: a network of thirty one
      regional drug surveillance centres, located to provide convenient proximity to
      health care professionals; a causality assessment method, compulsory for all
      persons involved in drug surveillance, to assess the causal relationship between
      an adverse effect and one or more drugs; if necessary, an additional evaluation
      of the causal relationship will be performed using pharmaco-epidemiology methods;
      a Technical committee and a National Commission of Drug Surveillance which
      centralize and assess all the data in order to provide a consensual advice to the
      relevant authorities on necessary measures, to prevent, or reduce a drug related
      adverse effect; in the case of an inquiry, the drug surveillance department of
      the pharmaceutical company and the network of regional drug surveillance centers
      will pool their data with the aim to exchange information and ideas.

PMID- 9916333
TI  - [Practitioner's freedom to prescribe in relation to the requirements of the AMM,
      the medical references and the socioeconomic constraints].
AB  - The freedom of prescription is registered in texts which have a legislative
      value: le Health Code, the social security code, the medical deontology code. The
      control of prescription conditions for certain classes of medicines meets some
      economic and Health targets. The authorization to put products on the market
      concerns the medicines produced industrially. The instructions and opposing
      medical references are tools that could allow "the medicalized control of Health
      cost evolution" mandated by the National Convention which links the liberal
      doctors and the organisms of social protection. Their non-respect can involve
      sanctions for the doctors who have signed the convention but do not constitute at
      the very outset a fault in the words of civil liability. The freedom of
      prescription, information and consent of the patient are undissociable. In the
      name of freedom the responsibility of the practitioner is involved. The faults
      are classified in two categories: breach of medical humanism, breach of rules of
      medical art. The aim of the regulation consists in the optimum prescription.
      Freedom and regulation go together with professionalism and good citizenship.

PMID- 9916334
TI  - [Information, education and assistance to the patient].
AB  - Information, Training and Assistance to patients are an ethical requirement for
      the prescriber as well as a necessary support to setting up the treatment best
      suitable to meet optimal efficacy expectations. Several phases with regard to
      providing information to patients can be considered: good knowledge of the
      patient, providing the patient with information regarding his or her disease,
      treatment, the overall medical assistance. Limits, hindrance and possible risks
      for the patient in providing medical information, are highlighted.

PMID- 9916335
TI  - [From the prescription to the patient: contribution of the pharmacist or
      pharmaceutical opinion].

PMID- 9916336
TI  - [Drug prescriptions for the elderly].
AB  - The assessment od drugs taken by elderly people remains a difficult subject since
      epidemiological data on drug intake in this population is very limited. In a
      study undertaken in the context of the PAQUID project, drug use was screened in a
      group of 3,777 elderly people living at home in the Gironde and Dordogne regions
      of south-west France. In this group, 89.1% of subjects take at least one drug per
      day, with an average daily intake of 4.1 drugs by 41% of the group. One third of
      these elderly people take a benzodiazepine drug. Excessive intake of drugs by
      elderly people is a phenomenon encountered in Scandinavia and Italy but not in
      the United Kingdom.

PMID- 9916337
TI  - [Prescription of non-steroidal anti-inflammatory drugs].
AB  - Non steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and largely
      used over the counter, especially for analgesic purposes in the most commonly
      nociceptive painful disorders. Unfortunately, NSAID use is associated with a high
      rate of side effects which account for 9% to 25% of the reports to the drug
      surveillance centres all over the world. Interestingly, severe adverse events are
      partly preventable provided some recommendations are followed. First, individual
      risk factors (old age, gastrointestinal history, possible drug interaction, ...)
      should be carefully assessed in order to take particular preventive measures
      (coprescription of misoprostol or omeprazole, treatment of a preexisting
      dehydration, ...) or ensure specific monitoring. Second, NSAIDs should be used at
      the lowest effective dosage after consideration of safer alternatives. Third,
      NSAIDs should be combined with other analgesics with the aim of reducing NSAID
      dosage. Finally, the patients should be informed about the main side effects of
      NSAIDs.

PMID- 9916338
TI  - [Prescription of psychotropic drugs; use, misuse and abuse].
AB  - The prescription of psychotropic drugs in France rises questions dealing with
      public health and medical ethics. Mental disorders are too often turned into
      target-symptoms for psychotropic drugs minimizing the importance of individual
      psychism which requires specific help. Prescribed either excessively or
      insufficiently psychotropic drugs are used mainly in general practice according
      to questionable criteria. The importance of a good initial training in
      pharmacology and therapeutics is stressed. A post graduate medical training
      totally independent is the only warranty of a prescription adapted to patients'
      needs.

PMID- 9916339
TI  - [Synthesis and conclusions. Factual therapeutics, good practices and decision
      personalized to the patient].

PMID- 9916340
TI  - [New markers of the risk of preterm delivery].
AB  - Preterm births account for 5.9% of all deliveries in France, a proportion that
      has not changed noticeably over the past 30 years. Neither risk scores nor
      systematic digital vaginal examinations at prenatal consultations have helped to
      diminish the incidence of prematurity. Because an indispensable prerequisite to
      reducing this incidence is better identification of the patients at risk, new
      approaches towards this end have been proposed in recent years. Various studies
      have shown that fetal fibronectin in cervico-vaginal secretions between 23 and 36
      weeks' gestation can be used to identify, among patients with uterine
      contractions and clinically observable modifications of the cervix, a subgroup of
      women at very high risk of preterm delivery. Systematic assays for fetal
      fibronectin among low-risk women are not, however, valuable, because of both the
      low prevalence of preterm delivery in such a population and the poor positive
      predictive value. Transvaginal ultrasound of the cervix furnishes an objective
      and noninvasive method for ascertaining cervical status. Various studies have
      shown that, among patients presenting signs of preterm labor, the risk of preterm
      birth is higher when the cervical length, measured with ultrasound, is less than
      a given cut-off point (the good predictive values of which have been
      ascertained). Transvaginal ultrasound is also useful among the general
      population. Measurement of cervical length thus ought to be incorporated into the
      routine ultrasound performed in this population. Moreover, in addition to
      cervical shortening, other abnormal ultrasound findings independently associated
      with an increased risk of preterm delivery include the following: dilatation of
      the internal os, wedging, funneling (protrusion of amniotic membranes into the
      cervix), dynamic changes in the degree of dilation of the cervical canal (opening
      of the internal os or protrusion of membranes) observed, either spontaneously
      during contractions or after pressure on the fundus. Because fibronectin assays
      and cervical ultrasound allow patients at risk of true preterm labor to be
      identified earlier and more accurately, they should improve the chances that
      tocolytic treatment will succeed. They also ought to reduce the iatrogenic
      disorders related to prevention of preterm birth (excessive tocolysis and
      extended hospitalizations) without raising the incidence of such births.

PMID- 9916341
TI  - [Procalcitonin, a marker of bacterial meningitis in children].
AB  - Procalcitonin (PCT) is a new marker connected to systemic bacterial infection.
      Blood values are parallel to the severity of the disease. In the present
      Knowledge on PCT, the usefulness is focused on acute pediatric pathology, ICU,
      and the follow up of grafts and surgery. This paper dwells on the interest in the
      differential diagnosis for meningitis (viral versus bacterial). At the opposite
      of CRP and IL6, a very clear cut off for all the cases has been found. The cut
      off in this study is about 2-3 micrograms/l. PCT, at the difference of cytokines
      is a very stable molecule in the blood sample. Also a very small quantity of
      serum (or plasma) 20 microliters is sufficient for one assay. In the future, a
      point of care assay will be available and should be very interesting in the
      emergency wards (pediatric or adult ICU). The origin of PCT seems to be--but
      perhaps not exclusively--mononuclear cells. The absence of an animal model
      (except monkeys) is actually a difficulty to progress.

PMID- 9916342
TI  - [Procoagulant nature of fibrin].
AB  - The main threat from a beginning thrombus is that it tends to grow, and hence
      become occlusive and/or embolise. Although the progressive nature of thrombi has
      been recognised since a long time, the mechanisms behind thrombus growth remain
      only partially resolved. In order to investigate in what ways thrombi can
      themselves become foci of further thrombin -and hence fibrin-formation, we
      studied the effect of fibrin clots on thrombin generation in platelet poor--and
      platelet rich plasma (PPP and PRP). The thrombin always adsorbed on a natural
      fibrin clot is not inactivated by plasmatic antithrombins and could be shown to
      retain its ability to enhance further thrombin formation by activation of
      clotting factors V and VIII as well as of blood platelets. To our surprise,
      fibrin clots without any active thrombin adsorbed, because they were obtained by
      a snake-venom enzyme or because thrombin had been inhibited, retained their
      capacity to activate blood platelets and make them procoagulant. The activation
      could be shown to be due to a rearrangement of cell-membrane phospholipids, by
      which the procoagulant species (phosphatidyl serine and phosphatidyl
      ethanolamine) became available at the outer cell surface. The platelet membrane
      receptor involved could be recognised as glycoprotein Ib, interacting with fibrin
      through the plasma protein von Willebrand factor (vWf). In fact it appeared that
      vWf is indispensable for the generation of thrombin in PRP, with or without added
      clot. This assigns a new and hitherto unknown role to vWf. Our results also show
      that fibrin is far from being the inert end-product of coagulation but is a
      potent activator of blood platelets and by this action may foster thrombin
      generation and hence further fibrin production. We surmise this mechanism to be
      instrumental in the progression of thrombotic processes.

PMID- 9916343
TI  - [Constitutional thrombopathies: from the clinical description of rare diseases
      (Glanzmann thrombasthenia and Bernard-Soulier syndrome) to the development of new
      antithrombotic agents].
AB  - The study of exceptional thrombocytopathies has led to considerable progress in
      the understanding of normal and pathologic haemostasis. Thus, precise
      structure/function relationships were able to be established. The lack or the
      abnormalities of the glycoprotein IIb/IIIa complex is responsible for the
      complete defect in platelet aggregation characterizing Glanzmann's
      Thrombasthenia, while the lack or the abnormalities of the glycoprotein Ib/IX/V
      complex is responsible for the defect in platelet adhesion to the subendothelium
      noted in the Bernard-Soulier syndrome. The bases for these abnormalities are now
      known at the molecular level. Recent data also underline the role of these
      glycoproteinic complexes as receptors for platelet activation; besides an
      involvement of the GPIIb/IIIa complex in adhesion and of the GPIb/IX/V complex in
      platelet aggregation, von Willebrand factor dependent, were newly evidenced. New
      antithrombotic agents directed against the GPIIb/IIIa complex are currently being
      tested in large clinical trials, especially in cardiovascular diseases. In the
      future, the inhibition of the GPIb-IX-V/von Willebrand factor axis should permit
      the development of a new class of antithrombotics, perhaps even more promising
      since they will act at the very early phases of primary hemostasis.

PMID- 9916344
TI  - [Evolution of monoamine receptors and the origin of motivational and emotional
      systems in vertebrates].
AB  - The evolving vertebrate nervous system was accompanied by major gene duplication
      events generating novel organs and a sympathetic system. Vertebrate neural
      pathways synthesizing catecholamine neurotransmitters (dopamine and
      noradrenaline), were subsequently recruited to process increased information
      demands by mediating psychomotor functions such as selective attention/predictive
      reward and emotional drive via the activation of multiple G-protein linked
      catecholamine receptor subtypes. Here we show that the evolution of these
      receptor-mediated events were similarly driven by forces of gene duplication, at
      the cephalochordate/vertebrate transition. In the cephalochordate Amphioxus, a
      sister group to vertebrates, a single catecholamine receptor gene was found,
      which based on molecular phylogeny and functional analysis formed a monophyletic
      group with both vertebrate dopamine D1 and beta adrenergic receptor classes. In
      addition, the presence of dopamine but not of noradrenaline was assayed in
      Amphioxus. In contrast, two distinct genes homologous to jawed vertebrate
      dopamine D1 and beta adrenergic receptor genes were extant in representatives of
      the earliest craniates, lamprey and hagfish, paralleling high dopamine and
      noradrenaline content throughout the brain. These data suggest that a D1/beta
      receptor gene duplication was required to elaborate novel catecholamine
      psychomotor adaptive responses and that a noradrenergic system specifically
      emerged at the origin of vertebrate evolution.

PMID- 9916345
TI  - [Heparin-induced thrombopenia: significance and difficulties of precise
      identification of the immunologic mechanism].
AB  - Heparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic
      adverse reaction which is a rare but potentially very severe accident. Its
      diagnosis is important for epidemiologic and drug surveillance studies and in
      order to decide the most appropriate treatment. Its importance is enhanced since
      there is no gold standard diagnostic criteria. In clinical practice the diagnosis
      is based on a group of criteria related to clinical events and laboratory tests.
      We have established a score based on anamnestic criteria which allowed us to
      evaluate and compare two different laboratory tests: a platelet aggregation test
      (PAT) and a test for the detection of heparin dependent antibodies (Heparin
      Platelet Induced Antibodies or HPIA). The functional test PAT which is commonly
      used in expert laboratories detects antibodies inducing platelet aggregation in
      the presence of heparin. The HPIA test more recently developed is an ELISA test
      which detects antibodies directed at heparin-platelet factor 4 complexes. The
      relative value of theses two methods for the diagnosis of HIT is not well
      documented. We have analysed the results of these two tests in 273 consecutive
      patients with a suspicion of HIT. The results were concordant in 70% of patients.
      In selecting the patients with the lowest and the highest probability of HIT
      according to the score, PAT was found a more sensitive and HPIA a more specific
      test than the other. At low probability PAT is more often positive than HPIA 18%
      and 9% respectively. No test is 100% reliable, the specificity being limited for
      both tests since in about 20% of cases one or both tests are negative contrasting
      with a highly probable HIT. In this last group of patients, PAT was more
      frequently positive (86%) than HPIA (72%). Both tests are negative in 6% of
      patients suggesting the existence of presently unknown antigenic targets.
      Considering a group of 19 patients with a high probability of HIT, we have found
      antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a
      HPIA positive and a PAT negative encountered in 8% of patients may be explained
      by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are
      unable to promote platelet aggregation via the CD32 platelet membrane receptor.
      This work suggests than neither test is 100% reliable and that they play a
      complementary role in the diagnosis of HIT. The potential advantage of using both
      tests should be confirmed in complementary studies

PMID- 9916346
TI  - [Reproducibility and prognostic value of histopathological classifications of
      malignant lymphomas. Prolegomena for the 1st international classification
      proposed by WHO. Group of the non-Hodgkin's Malignant Lymphoma Classification
      Project].
AB  - Different histopathologic classifications have been used in the study of
      malignant lymphomas. The clinical relevance (reproducibility, prognostic value)
      has not been precisely studied. The "non-Hodgkin's lymphoma classification
      project" has been organized to study a cohort of 1,403 cases in 9 sites around
      the world consisting of consecutive patients seen between 1988 and 1990 in order
      to have a good follow-up. The reproducibility of the up-dated Kiel and the ILSG
      (REAL) classifications between the 5 visiting expert hematopathologists was
      pretty good, at least 85% for the majority of the entities. According to survival
      curves, the lymphomas can be stratified in 4 different groups. Comparison with
      the international prognostic index demonstrate that for therapeutic strategy both
      histopathology and index should be used. The results bring a good support to the
      project of the WHO to propose the first international classification of lymphomas
      based on both forme classifications.

PMID- 9916347
TI  - Varicella-zoster virus disease and epidemiology: seeking better control
      strategies--Part 1.

PMID- 9916348
TI  - Disease surveillance--WHO's role.

PMID- 9916349
TI  - Health information policy: on preparing for the next war.
AB  - As policymakers demand more and better information about health care, the private
      health information technology industry is investing heavily to produce the
      "paperless clinical enterprise" of the future: the infrastructure that will be
      required to satisfy those demands. Developments on a number of policy fronts,
      however--from medical privacy legislation to clinical software regulation to
      "telehealth"--suggest the need for a conscious health information policy that
      will inform the debate in each niche area with a larger sense of whether public
      policy will promote or retard private innovation in this area. Given the stakes
      involved, and the immediacy of the issues, leadership in this direction is badly
      needed.

PMID- 9916350
TI  - Release 0.0: clinical information technology in the real world.
AB  - The industrialization of medical care delivery, compelled by fifteen years of
      reimbursement reform, has given rise to a commercial health information
      technology (HIT) industry. Well financed by Wall Street, the HIT industry offers
      a variety of ready-made solutions designed to transform a health care
      organization's raw data resources into useful clinical information. Many of the
      resulting clinical decision-support products are encumbered by numerous
      insurmountable intellectual and technical problems and, as a consequence, meet
      with cultural resistance from physicians. The long-awaited but costly
      implementation of electronic medical records (EMRs) will make these pioneering
      but flawed efforts obsolete, if EMR development successfully exploits recent
      technological breakthroughs and the ongoing consolidation of health care
      organizations.

PMID- 9916351
TI  - 'After the chaos': expected benefits of health information management.

PMID- 9916352
TI  - Pursuing the promise of an information-age health care system.

PMID- 9916353
TI  - Need for standards in health information.

PMID- 9916355
TI  - Looking back on health care reform: 'no easy choices'. Interview by Larry Brown.

PMID- 9916354
TI  - Protecting privacy to improve health care.
AB  - No comprehensive federal law now protects the privacy of people's medical
      records. The Health Insurance Portability and Accountability Act of 1996 mandates
      that if Congress fails to enact such legislation by August 1999, the secretary of
      health and human services must promulgate regulations. This paper argues that
      health privacy legislation is necessary both to improve patient care and to
      enhance the reliability of the health information used for research and public
      health initiatives. Within this framework I review pending federal health privacy
      legislation and make recommendations for moving forward.

PMID- 9916356
TI  - Bundled Medicare payment for acute and postacute care.
AB  - One legislative policy option for controlling postacute care costs is for
      Medicare to make a "bundled" payment to hospitals to cover episode costs: acute
      plus postacute care costs. But a bundled payment might not match the costs of
      treatment as well as payment now does under Medicare's prospective payment system
      (PPS). Simulating hospital margins with and without postacute care costs, this
      paper finds that risks to the typical hospital would not increase under postacute
      care bundling. A central characteristic of a bundled payment is that it would
      cover multiple providers. From this characteristic comes bundled payment's major
      strength: cost containment.

PMID- 9916357
TI  - Emerging trends in mental health policy and practice.
AB  - The continuing deinstitutionalization of patients in public mental hospitals and
      the growth of managed care are fundamentally altering mental health practice.
      Managed care provides opportunities for achieving parity of insurance coverage
      between mental and physical illness, but serious problems persist in integrating
      mental health, substance abuse, and general medical care and assuring an
      appropriate range of services and programs for persons with serious mental
      illness residing in community settings. Hospital and community care are poorly
      coordinated, and hospital care needs to be integrated into a more balanced system
      of services. Important new roles are emerging for purchasers, patient advocates,
      and mental health authorities.

PMID- 9916358
TI  - National health expenditures in 1997: more slow growth.

PMID- 9916359
TI  - Trends in health care R&D and technology innovation.

PMID- 9916360
TI  - Health benefits for the terminally ill: reality and perception.
AB  - This paper examines the availability and scope of hospice benefits as well as
      employers' attitudes and knowledge about care for the terminally ill. Data are
      drawn from a national random sample of 1,502 employers with 200 or more workers
      and from focus groups with employee benefits managers and their insurance
      advisers, brokers, and consultants. Major findings are that 83 percent of
      employers offer explicit hospice benefits, with most other firms covering hospice
      through high-cost case management. Most employers support the concept of hospice
      care because they believe that it reduces medical expenses.

PMID- 9916361
TI  - Bringing collaboration into the market paradigm.
AB  - The market competition paradigm assumes that health plans will compete on many
      factors, including quality of care. Unfortunately, for many reasons health plans
      have not made a substantial effort to distinguish themselves on quality. The
      antitrust laws that are designed to protect competition allow selective
      collaboration among competitors for various purposes, including quality
      improvement. Within antitrust constraints, specific opportunities exist for
      competing health plans to collaborate to improve quality. Their success will
      depend on purchasers' ability to demand such collaborative efforts as part of
      their overall purchasing strategy.

PMID- 9916362
TI  - Regaining public trust.

PMID- 9916363
TI  - The role of anecdotes in regulating managed care.

PMID- 9916364
TI  - The elusive new federalism.

PMID- 9916365
TI  - 'Assessing the new federalism' and state health policy.

PMID- 9916366
TI  - BadgerCare: a case study of the elusive new federalism.

PMID- 9916367
TI  - Disparities in access to Medicare managed care plans and their benefits.
AB  - Concern about the variation in rates paid to Medicare managed care plans across
      the United States led to the passage of major reforms of formulas for setting
      these rates as part of the Balanced Budget Act (BBA) of 1997. However, observers
      have focused much more on the variation in the rates per se than on the disparity
      in benefits offered by these plans and in the premiums they charge. This analysis
      shows that there is considerable variation in the range of risk plans available
      to Medicare beneficiaries, the premiums charged, and the benefits offered and
      that the variation is strongly related to the payment made by the Health Care
      Financing Administration (HCFA) on behalf of the beneficiary and to the
      beneficiary's area of residence.

PMID- 9916368
TI  - Can Medicare beneficiaries make informed choices?
AB  - This DataWatch assesses Medicare beneficiaries' understanding of the differences
      between their managed care and fee-for-service Medicare options. A telephone
      survey was used to evaluate knowledge levels among 1,673 beneficiaries residing
      in five Medicare markets with high managed care penetration. Half of the sample
      were enrolled in health maintenance organizations (HMOs) and half in the
      traditional Medicare program. The findings show that 30 percent of beneficiaries
      know almost nothing about HMOs; only 11 percent have adequate knowledge to make
      an informed choice; and HMO enrollees have significantly lower knowledge levels
      of the differences between the two delivery systems. These findings have
      implications for educating beneficiaries about their expanded choices.

PMID- 9916369
TI  - Quality of care for two common illnesses in teaching and nonteaching hospitals.
AB  - Teaching hospitals are recognized for treating rare diseases, but their value in
      caring for common illnesses is less clear. To assess quality of care for
      congestive heart failure and pneumonia, we reviewed the medical records of
      Medicare beneficiaries in major teaching, other teaching, and nonteaching
      hospitals in four states. Overall quality was rated better in major and other
      teaching hospitals than in nonteaching hospitals by physician reviewers and
      explicit process criteria, but the results varied for different subsets of
      explicit measures. Future studies should assess whether outcomes differ between
      teaching and nonteaching hospitals.

PMID- 9916370
TI  - Alzheimer's disease care: costs and potential savings.
AB  - A cross-sectional study of 679 Alzheimer's disease patients from thirteen sites
      in nine states provides a unique opportunity to estimate costs of Alzheimer's
      disease care by disease stage and care setting and to explore potential areas of
      cost savings. In 1996 annual costs of caring for patients with mild, moderate,
      and severe Alzheimer's disease were $18,408, $30,096, and $36,132, respectively.
      Monthly savings of $2,029 in formal services are possible if disease progression
      can be slowed. Annual institutional cost savings of $9,132 also are achievable if
      alternative residential settings are used.

PMID- 9916371
TI  - Medicaid managed care programs in rural areas: a fifty-state overview.
AB  - Interviews with state Medicaid officials reveal that although managed care
      programs have been implemented in rural areas, participation remains behind that
      of urban areas. Many states aim to create a statewide Medicaid managed care
      program and are struggling to overcome barriers that are greater in rural areas,
      including providers' resistance, lack of commercial managed care, and inadequate
      supply of providers. Many have modified contracting strategies and shown
      flexibility regarding interpretations of travel standards, twenty-four-hour
      coverage requirements, and primary care case management requirements, to
      implement programs in rural environments.

PMID- 9916372
TI  - Does a fixed-dollar premium contribution lower spending?
AB  - In a multiple-option health benefits program, the employer's premium contribution
      determines the incentives facing employees and participating health plans.
      Advocates of managed contribution argue that a fixed-dollar contribution policy
      will result in lower health spending by encouraging cost-conscious choices by
      employees and price competition among plans. The University of California (UC),
      which adopted a fixed-dollar contribution policy in 1994, provides a useful case
      study for assessing this claim. This DataWatch documents the effect of this
      policy on health maintenance organization (HMO) premiums and per employee health
      spending in the UC health benefits program.

PMID- 9916373
TI  - Accountability without health care data banks.

PMID- 9916374
TI  - Fundamentals of performance measurement.

PMID- 9916375
TI  - [Clinical epidemiology of coronary disease].

PMID- 9916376
TI  - [Reactions and interactions of drugs].

PMID- 9916377
TI  - A new class of pyrrolidin-2-ones: synthesis and pharmacological study. II.
AB  - The anticonvulsant activity of a second series of pyrrolidin-2-ones (1-2a, 1-4b,
      1-9c) was tested on pentylenetetrazole (PTZ) treated mice. The compounds were
      obtained by acylation of N-(3'-aminopropyl)-2-pyrrolidinone with the suitable
      acid chloride.

PMID- 9916378
TI  - [Suspension of vaccination for hepatitis B. No scientific justification for the
      plan].

PMID- 9916379
TI  - Thiamin and riboflavin status of medical inpatients.
AB  - Thiamin status was assessed by erythrocyte transketolase activity (ETKA) and
      thiamin pyrophosphate effect (TPPE) and riboflavin status by erythrocyte
      glutathione reductase activity (EGRA) and activity coefficient (AC) in 165
      medical inpatients in Ramathibodi Hospital. Based on TPPE > 15 per cent, 9 per
      cent of the medical inpatients had thiamin depletion. Most of them were patients
      with renal, cardiovascular, hematological and infectious diseases. Based on AC >
      or = 1.2, 17 per cent of these inpatients had riboflavin depletion. Most of them
      were patients with pulmonary, cardiovascular and hematological diseases. Only one
      patient with pulmonary disease had both thiamin and riboflavin depletion. The
      proportion of thiamin depletion (2/37) in subjects with thiamin supplementation
      (mean 32.4, median 6, mode 2 md/d) tended to be less than those without (9/98).
      But, subjects with riboflavin supplementation (mean 3.3, median 4, mode 1 md/d)
      had the proportion of riboflavin depletion (0/31) significantly (Z-test, p <
      0.005) lower than without supplementation (23/104). The data suggested that
      although the usual dose of vitamin supplementation in medical inpatients is
      beneficial thiamin depletion can still be present in catabolic patients.

PMID- 9916380
TI  - A new reference line for measuring the liver size in healthy newborns.
AB  - The liver span in 103 healthy newborns was determined by percussion and
      ultrasonic scanning along the midclavicular line (MCL) and the umbilicus-nipple
      line (UNL). The liver size (mean +/- SD) measured along the MCL was 4.1 +/- 0.7
      cm (range 2.7-5.7 cm) by percussion and 4.0 +/- 0.8 cm (range 1.9-6.2 cm) by
      ultrasonic scanning. Along the UNL, the liver size determined by percussion was
      4.0 +/- 0.7 cm (range 2.8-5.8 cm) and 3.7 +/- 0.8 cm (range 1.4-5.8 cm) by
      ultrasonic scanning. The correlation coefficient between liver measurement along
      the MCL and UNL by percussion and ultrasonic scanning was good and statistically
      significant (r = 0.95, p < 0.0001 and r = 0.83, p < 0.02, respectively). The new
      reference line for measuring the liver size, the UNL, should allow the clinician
      to determine the liver size more easily and may improve the accuracy in examining
      the liver.

PMID- 9916381
TI  - Effects of long-term treatment with depot medroxy progesterone acetate for
      contraception on estrogenic activity.
AB  - The aims of this study were to evaluate the serum estradiol level and the
      estrogenic activity in long-term DMPA users. From 1st January 1996 to 31st
      December 1996, fifty healthy women receiving DMPA for contraception for more than
      36 months were recruited to the study. From the study, it was found that the mean
      duration of DMPA use was 59.1 +/- 30.7 months, the mean serum estradiol was 52.7
      +/- 15.1 pg/ml and these women did not have problems of estrogen deficiency. This
      study revealed that long-term treatment with DMPA should not have any adverse
      effects on estrogenic activity.

PMID- 9916382
TI  - Methadone maintenance: results of treatment in heroin addict at Thanyarak
      Hospital (1990-1996).
AB  - Methadone maintenance is a treatment program designed for chronic heroin addicted
      patients. The purpose is to make them maintain their productive function and
      adaptive social behavior. The retrospective descriptive study was done from 1990
      to 1996. 195 cases joined the Methadone Maintenance Program (MMP) during this
      period. 188 cases were men and 7 cases were women. The average age was 31.9 +/-
      7.2 yr. (19-49 yr. old). 105 cases were single and 90 cases were married. 155
      cases were labourers (79.2%). 159 cases (81.5%) used more than 500 mg of heroin a
      day, it may be assumed that they spent 327 +/- 159 baht a day ($13 +/- 5). The
      duration of heroin usage before MMP was 8.7 +/- 5.4 yr. (4-25 yr.) In and out of
      the detoxification treatment program was 12.7 +/- 10.1 times (4-44 times). We
      found that 11 cases successfully decreased and then stopped the methadone. 32
      cases were in the program for more than 1 year and also joined the program until
      the end of this study. This meant that 43 cases (22%) were successful in stopping
      their heroin addicted behavior. The average dose of methadone administration was
      61.5 mg (40-80 mg mostly). The average time for the patients attending the
      program was 8.2 months (2-80 months). 38 cases who attended the program for more
      than 1 1/2 years were in the older-aged and married group. We found no difference
      in the previous heroin usage or methadone dose in these patients before they
      attended the MMP. The 32 cases which remained on MMP used mostly less than 40 mg
      of methadone a day. Two-thirds of the cases discontinued the program due to their
      positive urine test findings for heroin up to 8 times. Although the MMP was a
      good way to decrease the heroin addicted behavior, it's not a promising way to
      stop this problem.

PMID- 9916384
TI  - The patellar tilt angle: correlation of MRI evaluation with anterior knee pain.
AB  - The purpose of this study was to analyze the degree of patella tilt and its
      correlation with the symptoms of anterior knee pain. We used magnetic resonance
      imaging (MRI) to measure the angle of patella tilt. The patients (n = 128) were
      classified into two groups. Group 1 (n = 78) included patients who had never had
      symptoms of anterior knee pain but had MRI for evaluation of the menisci and the
      ligaments. Group 2 (n = 50) included patients who had MRI for evaluation of
      anterior knee pain syndrome. Patients who had gross deformities like patellar
      dislocation, tricompartmental osteoarthritis, or inflammatory arthritis were
      excluded. The average patella tilt angle was 6.3 (SD = 3.9) and 12.8 (SD = 8.4)
      degrees, respectively, for the two groups of patients. Twenty-three patients in
      group 2 underwent arthroscopy because of failure of conservative treatment, and
      the average patella tilt angle in this subgroup was 16.4 degrees. Our study
      suggests that patella tilt angle is correlated with the symptoms of anterior knee
      pain, and indicated that the cause of pain came from the tight lateral
      retinaculum. In addition, MRI was found to be an accurate and reproducible method
      of measurement of the patellar tilt angle.

PMID- 9916383
TI  - The relationship of the axillary nerve and the acromion.
AB  - The relationship of the axillary nerve in 77 cadavers was studied. The distance
      of the axillary nerve from the angle of the acromion is between 43 to 82 mm (mean
      = 63 mm). The distance from the axillary nerve to the tip of the acromion varies
      from 47 to 89 mm (mean = 67 mm). The distance in the female is less than that in
      the male. The length of the acromion and of the arm are not correlated with the
      distance between the axillary nerve and the acromion. In addition, the course of
      the axillary nerve is not constantly parallel to the lateral border of the
      acromion. Therefore, the acromion is not a good surgical landmark for locating
      the axillary nerve.

PMID- 9916385
TI  - Nonadherence in tuberculosis treatment among HIV patients attending
      Bamrasnaradura Hospital, Nonthaburi.
AB  - OBJECTIVE: To determine the clinical manifestations, outcome and nonadherence, in
      tuberculosis (TB) among HIV patients in Bamrasnaradura Hospital, Nonthaburi.
      DESIGN: A retrospective cohort study; hospital record files were reviewed over 11
      months. A total of 200 consecutive HIV patients were entered and followed for a 6
      months period of their TB treatment. Sociodemographic data, symptoms and signs
      and results of investigation tests were recorded at the time of presentation,
      while diagnosis, and clinical outcome were done at the end of the follow-up time.
      RESULTS: Extrapulmonary tuberculosis (58%) was more common than pure pulmonary
      involvement (42%). Lymphadenopathy (52%) was the commonest sign on physical
      examination. Chest X-rays were positive in 55 per cent cases, while AFB
      examination was positive in 48.5 per cent from the sputum and 46 per cent from
      lymph node aspirate specimens. After 6 months of treatment, 30 per cent patients
      were still alive, 12 per cent had died, and 50 per cent were lost to follow-up.
      Factors such as low socioeconomic status (p < 0.001), being newly diagnosed with
      TB (p < 0.001), past history of TB (p < 0.003), etc., were statistically
      significant in predicting the likely nonadherence in TB treatment among HIV
      patients. CONCLUSION: In HIV-infected individual, tuberculosis presents more
      often with extrapulmonary involvement, and the diagnosis is not difficult. While
      treatment of tuberculosis is successful, patients' compliance is the biggest
      problem in managing them.

PMID- 9916386
TI  - The period prevalence of catamenial epilepsy at Prasat Neurological Institute,
      Bangkok.
AB  - The study was performed to assess the period prevalence of catamenial epilepsy in
      Thai female epileptic patients. Such a condition is defined as seizures related
      to menstruation which occur for at least 2 consecutive months within 1 patient
      during 4 days prior to and/or 6 days after the onset of menstruation. Patients
      with regular menstruation aged between 15-50 years attending the Out-Patient
      Department of Prasat Neurological Institute in Bangkok from 1 November, 1995 to
      31 January, 1996 were recruited. Patients and/or their relatives were interviewed
      directly or by telephone using a questionnaire concerning menstrual history,
      seizures related to menstruation and they were requested to record these data for
      2 further consecutive months. In cases where the interview could not be directly
      performed, a mailed questionnaire was used instead. All information was
      considered together with information reviewed from the OPD cards. Forty-six from
      467 epileptic patients were considered to have catamenial epilepsy. The period
      prevalence thus was 98.5 in 1,000 women at risk and the mode of frequency of
      seizure occurrence was 2 days before menstruation. Generalized seizure was found
      more common in these patients than partial seizure. In particular, general tonic
      clonic seizure and complex partial seizure were the most common for each type,
      respectively. About 70 per cent of the patients used more than 1 anti-convulsant
      drugs to control their seizures. Some have received other drug supplements to
      relieve seizure exacerbation but only mild improvement was observed. No change in
      body weights measured in 2 or 1 day before menstruation, on the first menstrual
      day and in 1 day after menstruation was demonstrated in all patients. The results
      suggest that catamenial epilepsy is one of the clinically significant problems of
      seizure control in Thai female epileptic patients and multifactors may be
      involved in this condition.

PMID- 9916387
TI  - Comparative studies of quality and bioavailability of methotrexate in Thai
      patients with rheumatoid arthritis.
AB  - The bioavailability of the two generic methotrexate oral preparations (Emtrexate,
      Pharmachemie Company, Holland and Methotrexate Remedica, Remedica, Cyprus as the
      test preparations), were compared to the innovator (Methotrexate Lederle,
      Lederle, U.S.A. as the reference) in 10 patients with rheumatoid arthritis. A
      single 7.5 mg oral dose of each preparation was given to the subjects in a
      randomized, double-blind, three-period crossover design with a 1 week washout
      period. Serum methotrexate concentrations were determined by using Fluorescence
      Polarization Immunoassay (Abbott TDx). No significant differences in
      pharmacokinetic parameters (AUC, Cmax, and Tmax) were observed between the test
      and reference preparations. The mean and 90 per cent CI of the ratio
      Emtrexate/Methotrexate Lederle and Methotrexate Remedica/Methotrexate Lederle of
      the Cmax, AUC0-8, and AUC0-alpha were 0.93 (0.87-1.00), 0.9 (0.82-0.98), 0.88
      (0.79-0.99) and 0.97 (0.93-1.02), 0.95 (0.90-0.99), 0.94 (0.86-1.02),
      respectively. These values were well within the acceptable bioequivalence range
      of 0.8-1.25. The mean and 90 per cent CI of Tmax difference between Emtrexate
      Methotrexate Lederle and Methotrexate Remedica-Methotrexate Lederle also
      overlapped the stipulated bioequivalence range of the Tmax differences of +/-
      0.25 hour. Thus, Emtrexate and Methotrexate Remedica were considered
      bioequivalent to the reference Methotrexate Lederle regarding the rate of
      absorption and the extent of absorption.

PMID- 9916388
TI  - A clinical study of Thai patients with spondyloarthropathy.
AB  - Eighty-eight Thai patients (61 males and 27 females) with spondyloarthropathy
      (SpA) were studied. Their mean age and mean duration of the disease were 25.97
      and 3.34 years respectively. In 16 cases the disease first appeared before the
      age of 16 or had juvenile onset. Eleven cases were ankylosing spondylitis (AS), 9
      were juvenile AS (JAS), 20 were Reiter's syndrome (RS), 4 were juvenile RS, 14
      were psoriatic arthritis (PsA), 27 were undifferentiated SpA (uSpA), and 3 were
      juvenile uSpA. Peripheral arthritis, especially oligoarthritis of the lower
      extremity joints, was the most common form of arthritis in all groups, except for
      PsA, where polyarthritis was common. Back pain and bilateral sacroiliitis were
      commonly seen in JAS and AS. Enthesopathy was not uncommon. Extra-articular
      manifestations were more common in RS patients. Acute inflammatory eye diseases
      were seen in 45 per cent of AS and 66 per cent of RS cases. In general, the
      clinical features of Thai patients with SpA were similar to those reported in
      other countries in Asia and the west.

PMID- 9916390
TI  - Vasa previa in Ramathibodi Hospital: a 10 years review.
AB  - Vasa previa is presented when fetal vessels cross the internal os as a
      velamentous insertion of the umbilical cord. This retrospective study is to
      review the diagnosis, the management, and the outcome of this condition over the
      10 years period in Ramathibodi Hospital, Bangkok, Thailand. Five cases were
      diagnosed after the rupture of membranes with only one case diagnosed prior to
      the rupture of membranes. The fetal mortality was 50 per cent. Despite continued
      advances in diagnostic procedures, vasa previa still presents considerable risk
      to the fetus.

PMID- 9916389
TI  - Premarital counseling clinic at Chulalongkorn Hospital.
AB  - BACKGROUND: The premarital counseling clinic at Chulalongkorn Hospital was
      established in 1978. The characteristics and sexual background were reviewed.
      AIM: To study characteristics, sexual background and choices of contraceptions of
      premarital couples attending the premarital counseling clinic at Chulalongkorn
      Hospital during the past ten years, (1988-1998). DESIGN: Descriptive study.
      MATERIAL AND METHOD: Two hundred couples (men (M) and women (W)) attending the
      premarital clinic at Chulalongkorn Hospital from July 1988 to January 1998 were
      recruited in the study. The counseling program included medical counseling, sex
      education and family planning counseling. The information of couples was recorded
      by the Family Planning Unit staff and the residents. RESULTS: The mean age was
      31.5 +/- 4.3 yrs. (M), 28.9 +/- 3.8 yrs. (W). Most of the couples had a
      bachelor's degree education (61.5%--M; 72%--W). Most of them were employees
      (64.0%--M; 60.0%--W), had an income of 10,000-20,000 baht per month (39.0%--M;
      38.0%--W) were Buddhist 97.0 per cent (M), 93.0 per cent (W). There were only 4
      couples who had an abnormal physical examination. 85.5 per cent of the men had
      had sexual experience before while it was only 23.0 per cent in women. Most of
      the men had frequent masturbation 3-4 times/month (31.5%) and most of the women
      had no masturbation (86.0%) at all. Most of the couples (71.5%) chose to have
      contraception (contraceptive pill 57.5% and condom 20.0%). CONCLUSION: Premarital
      counseling should be adjusted to the background of the couples. Most couples had
      a high income and education. Sex counseling is important for couples especially
      women. The propagation of premarital clinic encourages further study and to
      outreach the general population of Thailand.

PMID- 9916391
TI  - Fetal complete heart block: an expectant management.
AB  - Fetal complete heart block is a rare cardiac arrhythmia occurring in prenatal
      life. The diagnosis usually requires a multimodality approach of imaging
      technology especially M-mode and Doppler ultrasound. The management guideline is
      not conclusive. We presented 2 cases of fetal complete heart block diagnosed
      prenatally. The fetuses were closely monitored conservatively and delivered at
      term. Permanent cardiac pacemakers were performed neonatally with satisfactory
      outcomes.

PMID- 9916392
TI  - Transcatheter laser-assisted balloon valvulotomy as primary treatment in newborn
      with pulmonary atresia and intact ventricular septum.
AB  - We report our initial experience and the first case in Thailand in successfully
      performing transcatheter laser perforation of membranous pulmonary valve and
      subsequent balloon dilations of the valve in a 14-day-old baby with pulmonary
      atresia and intact ventricular septum. After the procedure, right ventricular
      angiograms revealed anterograde flow across the pulmonary valve. There was no
      major complication. Doppler echocardiography one week later demonstrated a
      pressure gradient across the pulmonary valve of 30 mmHg and right ventricular
      systolic pressure of 60 mmHg. Her peripheral oxygen saturation improved from 70's
      immediately after the procedure to 92-97 per cent at one-month after the
      procedure.

PMID- 9916393
TI  - Recurrent acute cerebellar ataxia of childhood following nonspecific respiratory
      tract infection.
AB  - Acute cerebellar ataxia in childhood following viral infection is a self-limited
      disease. The disease with recurrent course has rarely been reported. At the
      Department of Pediatrics, Ramathibodi Hospital, three children with recurrent
      episodes of acute cerebellar ataxia following nonspecific viral infection were
      encountered. The age at onset of each patient was 2 years, 18 months and 2 years
      old. The clinical symptoms were similar and improved rapidly after gluco
      corticoid was given. All patients recovered without residual deficit. Six, 5 and
      3 recurrent attacks of similar illness were noted in each patient respectively
      after the first episode. However, no further attack occurred after the age of 5
      years and the age of last follow-up was 17, 16 and 14 years old respectively. The
      pathogenesis of the recurrent episodes is uncertain. The abnormal immunological
      response is postulated.

PMID- 9916394
TI  - Head and neck mycetoma.
AB  - Two cases of eumycotic mycetomas in the head and neck region are reported. The
      first case is the localized mycetoma which involved only the soft tissue of the
      neck. It was completely excised and the patient needed no further treatment. In
      the second case, the lesion extensively involved the structures in the
      parapharyngeal space, submandibular space and carotid sheath. The upper limit is
      the skull base. The patient was treated by combination of wide excision with
      radial forearm flap and antifungal agents, however, the prognosis is fair.

PMID- 9916395
TI  - Congenital erythropoietic porphyria: a case report.
AB  - Congenital erythropoietic porphyria is a rare autosomal recessive disorder of
      heme synthesis resulting from deficiency of uroporphyrinogen III synthase
      (UROIIIS). It is the most severe porphyria. The clinical manifestations are
      markedly variable due to the different mutation in the UROIIIS gene. We recently
      diagnosed a case of congenital erythropoietic porphyria. A 9-year-old boy
      presented with recurrent ulcers on the skin especially dorsum of the hands and
      feet since aged 3. The physical examination revealed ulcers on the dorsum of the
      feet, mutilation of the fingers, fluorescent erythrodontia, and darkening and
      hypertrichosis of the sun exposed area. Laboratory findings showed mild
      hemolysis, red urine, increased serum alkaline phosphatase level, and
      fluorescence of the red blood cell and urine. The histopathology was consistent
      with porphyria. The urine and plasma porphyrin levels confirmed the diagnosis of
      congenital erythropoietic porphyria. The administration of oral ultracarbon and
      topical zinc oxide has been tried.

PMID- 9916396
TI  - Intrapulmonary teratoma: a report of three cases.
AB  - Three cases of intrapulmonary teratoma are described. A specific symptom of
      trichoptysis occurred in two patients. The other presented with only recurrent
      hemoptysis. All were treated by lobectomy of the affected lung. Pathologic
      examination in each specimen showed that the tumor had a cystic portion which was
      connected to the bronchial system and contained sebaceous material and pieces of
      hair. The solid portion consisted of tissues representing all three germ cell
      layers. The pathologic findings correlated well with the clinical symptoms and
      radiologic findings in the patients.

PMID- 9916397
TI  - Double annulus enlargement, Rastan-Manouguian's technique: a case report.
AB  - A 35-year old female patient underwent a double valve replacement. The operative
      findings revealed a small aortic annulus (about 17 mm in diameter). In order to
      implant the adequate-size prosthetic valve, the aortic and mitral annulus were
      enlarged using the technique described by Rastan and Manouguian. The annulus were
      enlarged with a patch of gel-sealed dacron graft. After the enlargement, the
      prosthetic valve No. 23A and 31M could be implanted in the aortic and mitral
      annulus, respectively. This is an effective technique to enlarge the aortic and
      mitral annulus in a double valve replacement procedure. The annular diameter
      could be increased approximately 30 per cent.

PMID- 9916398
TI  - The decline in medical ethics and professionalism.

PMID- 9916399
TI  - [123I-metaiodobenzylguanidine (MIBG) scintigraphy for the staging of
      neuroblastoma].
AB  - Nineteen children with neuroblastoma (aged 2 w.-7 y.o.) were studied to evaluate
      the optimal scan conditions for Iodine-123-Metaiodobenzylguanidine (MIBG)
      scintigraphy for accurate staging at the time of diagnosis. Six and 24 hours
      after an injection of 123I-MIBG, whole body image and truncal spot and SPECT
      images were obtained. Compared with other studies (CT or MRI and bone
      scintigraphy), each 123I-MIBG image was evaluated visually to investigate which
      image can demonstrate the extent of neuroblastoma most exactly. MIBG images
      demonstrated primary tumors in all patients, and metastatic lymphadenopathy in 8
      of 9 patients. Twenty-four hour SPECT images gave us the most detailed
      information about the extent of abnormal accumulation. As to bone and bone marrow
      lesions, 6 hour images were superior to 24 hour images in detectability.
      Moreover, MIBG showed many more lesions and more extended accumulation than the
      bone scan. 123I-MIBG scintigraphy was very useful in detecting neuroblastomas. In
      order to get the most valuable information, both delayed SPECT and early whole
      body planar images should be obtained.

PMID- 9916400
TI  - [Stepwise analysis of cerebral blood flow SPECT imaging on standard brain atlas
      in patients with dementia of Alzheimer's type].
AB  - Statistical parametric mapping (SPM) has been developed by Friston et al. to
      analyze focal changes in regional cerebral blood flow (rCBF) induced by brain
      activation. This automated and objective approach has the potential of being
      applied to single photon emission computed tomography (SPECT) image data sets.
      This study evaluated an automated analysis of N-isopropyl-p[123I]iodoamphetamine
      SPECT (123I-IMP) imaging in patients with dementia of Alzheimer's type (DAT)
      using statistical parametric mapping '95 (SPM'95). Eighteen patients with
      clinically diagnosed mild to severe DAT who were classified into two groups and
      ten normal control subjects were studied. The SPECT device used was a triple
      headed rotation gamma camera. All images were transformed into the standard
      anatomical space of the stereotaxic brain atlas of Talairach and Tournoux, and
      then smoothed. Statistical analyses were made between severe DAT, mild DAT and
      normal control groups. SPM analysis of 123I-IMP SPECT images revealed that the
      parietotemporal association areas and posterior cingulate gyri of both cerebral
      hemispheres were significantly decreased in CBF in mild DAT group compared to
      normal controls. In comparison of DAT groups, the right hippocampal area and
      basal forebrain were significantly decreased in CBF in severe DAT group. In
      conclusion, these results obtained by SPM analysis of SPECT images suggested that
      the right hippocampal area and basal forebrain followed the parietotemporal
      association areas and posterior cingulate gyri in the reduction of the rCBF in
      patients with DAT.

PMID- 9916402
TI  - [The relationship between discrepant areas on 201TlCl/123I-BMIPP myocardial
      scintigraphy, local wall motion, and glucose metabolism in patients with
      myocardial infarction].
AB  - In order to clarify the significance of the discrepancy between myocardial blood
      flow and fatty acid metabolism on 201TlCl/123I-BMIPP SPECT after acute myocardial
      infarction, we examined 52 patients (278 segments) with their first acute
      myocardial infarction using two-dimensional echocardiography and FDG-PET.
      Patients with Tl/BMIPP discrepancy in the acute stage showed higher FDG
      accumulation than those without Tl/BMIPP discrepancy. In the chronic stage,
      however, there was no significant difference between both groups. Patients with
      Tl/BMIPP discrepancy in the chronic stage had lower wall motion scores than those
      without Tl/BMIPP discrepancy. Significant improvement of the wall motion score
      was recognized in patients who showed Tl/BMIPP discrepancy in the acute stage.
      Patients were classified into stenosis and non-stenosis groups by the presence of
      significant stenosis on coronary angiography in the chronic stage. In the
      stenosis group, the Tl/BMIPP discrepancy did not show much change from the acute
      to chronic stage, but there was a significant decrease in the non-stenosis group.
      It was concluded that 201TlCl/123I-BMIPP myocardial SPECT is useful for
      predicting future improvement of wall motion and determining the residual
      ischemia in the chronic stage based on the presence or absence of this
      discrepancy.

PMID- 9916401
TI  - [Hepatic clearance of 99mTc-GSA in cases of postoperative biliary atresia--a
      retrospective comparison with hepatic clearance of 99mTc-PMT].
AB  - There are a few reports about usefulness of 99mTc-GSA liver scintigraphy (GSA
      imaging) for the evaluation of postoperative state of biliary atresia. However,
      comparison of significance for the disease between GSA imaging and 99mTc-PMT
      hepatobiliary imaging have not been reported. Fifty-six GSA imagings for 41
      postoperative biliary atresia patients were reviewed and their scintigraphic
      findings and the functional parameters were compared with those obtained from
      99mTc-PMT hepatobiliary imaging. In quantitative analysis, although the hepatic
      clearance of both tracers calculated by graphical analysis (Patlak plot) were
      well correlated in most cases, a discrepancy was observed in several cases with
      jaundice. The authors conclude that the hepatic clearance of 99mTc-GSA is a more
      accurate index of the hepatic reserve than that of 99mTc-PMT which can be
      influenced by hyperbilirubinemia and that the combination of both examinations is
      helpful to evaluate development of liver injury in postoperative biliary atresia
      patients.

PMID- 9916403
TI  - [Usefulness of myocardial scintigraphy with 99mTc-tetrofosmin for diagnosis in 2
      cases of acute coronary syndrome].
AB  - Patients with acute coronary syndrome require accurate diagnosis and treatment.
      We found that emergency myocardial scintigraphy with 99mTc-tetrofosmin was useful
      for diagnosis in 2 patients with acute coronary syndrome. The first patient was a
      66-year-old man, who was hospitalized with chest discomfort at rest. Blood tests,
      electrocardiography, and echocardiography revealed no unusual findings.
      Myocardial scintigraphy with 99mTc-tetrofosmin disclosed moderately reduced
      uptake extending from the anterior wall to the apex. Coronary arteriography
      revealed 75% stenosis of the left main trunk. He was diagnosed as having unstable
      angina pectoris and coronary bypass surgery was performed. The second patient was
      a 61-year-old man, who was hospitalized with chest discomfort. Slight
      leukocytosis and flat T waves in leads V5 and V6 on electrocardiogram were
      detected, but echocardiographic findings were not abnormal. Myocardial
      scintigraphy with 99mTc-tetrofosmin revealed a defect in the posterolateral wall.
      Coronary arteriography showed total obstruction of #14, and a diagnosis of acute
      myocardial infarction was established. PTCA of #14 was performed to achieve
      reperfusion.

PMID- 9916404
TI  - [99mTc(V)-DMSA accumulation in gynecomastia].
AB  - The accumulation of 99mTc(V)-DMSA in bilateral breasts was recognized in a 60
      year-old male with drug-induced gynecomastia. There are some reports describing
      99mTc(V)-DMSA accumulation in normal female breast, fibrous dysplasia of the
      breast and metastatic lesions of breast carcinoma, but to my knowledge, there
      have been no reports describing 99mTc(V)-DMSA accumulation in gynecomastia.

PMID- 9916405
TI  - [Assessment of global and regional LV function obtained by quantitative gated
      SPECT using 99mTc-tetrofosmin: comparison with left ventricular cineangiography
      and echocardiography].
AB  - The quantitative gated SPECT (QGS) software that has automatic edge detection
      algorithm of the left ventricle, is able to calculate LV volumes and visualize LV
      wall motion with perfusion throughout the cardiac cycle. We evaluated the
      reliability of global and regional LV function derived from QGS using 99mTc
      tetrofosmin by comparing with left ventricular cineangiography (LVG) and
      echocardiography (ECHO). In 22 cardiac patients, end-diastolic volume (EDV), end
      systolic volume (ESV) and ejection fraction (LVEF) were calculated. Using
      cinematic display, regional LV wall motion were scored on a 3-point scale (1 =
      normal, 2 = hypokinesis, 3 = akinesis; WMS). EDV, ESV and LVEF correlated well
      with those by LVG (p < 0.001 for each). Correlation between WMS derived from QGS
      and ECHO was high (r = 0.85, p < 0.001). There was an inverse correlation between
      WMS and LVEF (r = 0.77, p < 0.001). In conclusion, QGS is useful to evaluate
      global LV function. Regional wall motion evaluated by QGS is good enough for
      clinical application.

PMID- 9916406
TI  - [Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of
      hyperfunctioning parathyroid lesions in patients with hyperparathyroidism--a
      report of multicenter phase III clinical trials].
AB  - Phase III clinical study in 78 patients with hyperparathyroidism was performed to
      determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning
      parathyroid lesions. Except slight tremor in one patient, no adverse events were
      reported. No abnormal changes in clinical laboratories or vital signs were noted.
      The clinical utility of the agent was evaluated in 70 patients. Out of 108
      hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of
      their histology, numbers, or location. Specifically, single or ectopic lesions
      were detected with high sensitivity (97% and 100%, respectively). Sensitivity in
      53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is
      extremely high compared to the 201T1-99mTc subtraction method. Specificity in a
      group of PHP patients with single adenoma who underwent surgery was 100% (63/63),
      though in case of coexistent thyroid disease obviously interfered parathyroid
      images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the
      localization of hyperfunctioning parathyroid tissues. Especially, the fact that
      99mTc-MIBI detected ectopic glands with high specificity is a great advantage
      over the ultrasound or 201Tl-99mTc subtraction method.

PMID- 9916407
TI  - [Development of a high-resolution pinhole SPECT system using dual-head gamma
      camera for small animal studies].
AB  - We developed a high-resolution pinhole SPECT system using dual-head gamma camera
      (PRISM-2000XP) for small animal, and evaluated the performance of this system.
      Two pinhole-inserts (Pb) were mounted on the same unit, and it was not attached
      to the detector but the gantry of gamma camera. We designed two kinds of pinhole
      collimators with different rotating radii, 40 mm (Type-I) and 50 mm (Type-II).
      The diameter of the pinhole is 1 mm for both types. The field of view (FOV) and
      magnification were 45.8 mm phi and 4.25 for Type-I, 57.4 mm phi and 3.40 for Type
      II, respectively. We measured full width at half maximum (FWHM) of line spread
      function using a 99mTc line source. Measured FWHM values were 1.65 mm using Type
      I and 1.91 mm using Type-II at the center of FOV in the center slice. The volume
      sensitivity of this system was 8.54 kcps/MBq/ml (Type-I) and 5.68 kcps/MBq/ml
      (Type-II). We could observed 1.2 mm phi cold spot in the resolution phantom using
      Type-I. In conclusion, this system is available for SPECT measurement of small
      animal studies.

PMID- 9916408
TI  - [Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of
      thyroid, breast and lung/mediastinum tumors--a report of multicenter phase III
      clinical trials].
AB  - Phase III clinical study in 136 patients diagnosed or strongly suspected of
      thyroid, lung/mediastinum or breast cancer was performed to determine clinical
      utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were
      evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse
      events were reported. Seven abnormal changes in vital signs and 27 in clinical
      laboratories were noted, which were all judged as having no or unlikely
      relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected
      with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3
      were detected. Fifteen sites of false positive in 11 malignant tumor patients and
      5 sites in 6 patients with non-tumor disease were observed. Our study indicates
      that 99mTc-MIBI is a safe and excellent agent for the localization of tumors.
      Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high
      sensitivity is a great advantage over the other conventional imaging modalities.

PMID- 9916409
TI  - [Evaluation of the safety and clinical feasibility of exercise 99mTc-MIBI SPECT
      using one day protocol--multicenter phase III clinical trial report].
AB  - We evaluated the safety and clinical usefulness of the same day protocol of
      exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event
      was observed except for one case of transient hypotension caused by the exercise.
      More than 95% of stress images and all of the rest images were judged as
      "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in
      detecting coronary artery disease, and no statistical difference was observed
      between the results obtained with Re-Ex and Ex-Re protocols. The examination was
      "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We
      concluded that the same day protocol is a safe and useful method for diagnosing
      myocardial ischemia, which provides high image quality and valuable information.

PMID- 9916410
TI  - [Nosocomial pneumonia experienced in a community hospital].
AB  - To clarify the characteristic features of nosocomial pneumonia in a community
      hospital, we performed a clinical analysis of 147 patients (155 episodes) with
      nosocomial pneumonia. The following results were obtained. 1, Regarding the risk
      factors for nosocomial pneumonia, factors such as the patient whose age was over
      65 years, a duration of admission of over one month, performance status 4 and
      underlying respiratory diseases associated with the appearance of nosocomial
      pneumonia. 2, The causative microorganism isolated from the sputum of the patient
      with nosocomial pneumonia was frequently a multi-drug resistant microorganism
      such as Methicillin-resistant Staphylococcus aureus (MRSA). 3, regarding
      treatment, although several antibiotics were administered for a long time,
      mechanical ventilation was used on 31% of the patients, and steroid pulse therapy
      was carried out on 24%. The clinical efficacy was poor with a 50% mortality rate.
      The reason why treatment of nosocomial pneumonia was difficult is thought to be
      been related to the general condition of these inpatients and to the appearance
      of a multi-drug resistant, polymicrobial microorganisms.

PMID- 9916411
TI  - [Clinical study on fluconazole (FLCZ) in the treatment of primary pulmonary
      cryptococcosis].
AB  - We treated two cases of primary pulmonary cryptococcosis with fluconazole (FLCZ),
      the clinical usefulness of FLCZ was evaluated. FLCZ was administered orally in
      doses of 300 mg daily for about six months. Concentrations of FLCZ were measured
      in the serum of the two cases and in the bronchoalveolar lavage (BAL) fluid in
      one case. The following results were obtained: 1. Clinical cures were obtained in
      the two cases. 2. The serum levels of FLCZ was 15.1 microliters/ml, 13.6
      micrograms/ml two hours after administration of 100 mg in case 1, that of levels
      were 11.1 micrograms/ml, 8.9 micrograms/ml one hour and 4.5 hours, respectively,
      after administration of 100 mg in case 2. BAL was performed 4.5 hours after
      administration of 100 mg in case 2, the BAL fluid level of FLCZ was 0.7
      microgram/ml. 3. The minimal inhibitory concentration of FLCZ against one strain
      obtained from the cytology brush in case 1 was 4.0 micrograms/ml. 4. The
      cryptococcal antigen titer decreased with the improvement of clinical signs and
      the resolution of chest X-ray abnormalities within about six months, and there
      was no relapse. From these results, we consider that FLCZ is a useful antifungal
      agent for primary pulmonary cryptococcosis, and we therefore recommend a six
      month treatment.

PMID- 9916412
TI  - [Immunoglobulin production by human peripheral B cells against Staphylococcus
      aureus].
AB  - Immunoglobulin (Ig) production by human B cells in thymus-independent (TI) and 
      dependent (TD) immune response against Staphylococcus aureus was investigated in
      vitro. Highly purified human peripheral B cells were cultured either in the
      presence of formalinized Cowan I strain Staphylococcus aureus (SAC) or with anti
      CD3 stimulated T cells, and Ig content in supernatants was analyzed after 10 days
      of culture by specific sandwich ELISA. When activated with SAC in the absence of
      T cells, B cells produced minimal amounts of Ig. In the presence of interleukin-2
      (IL-2) or supplemental recombinant CD40 ligand plus IL-2, Ig production by SAC
      induced B cells was dramatically enhanced. When cultured with T cells stimulated
      with low concentrations of anti-CD3 or when cultured with smaller numbers of T
      cells, B cells produced large amounts of Ig, whereas T cells stimulated with
      higher concentrations of anti-CD3 or large numbers of T cells failed to induce
      effective Ig secretion by B cells. These findings suggest that TI immune response
      against Staphylococcus aureus is strongly enhanced in the presence of activated T
      cells in an antigen non-specific manner, indicating its critical role in the
      local humoral immune defense. Moreover, it is indicated that the secretion of Ig
      induced by TD antigens participates in the immune defense against Staphyloccocus
      aureus dependent on activated T cell/B cell ratio or an impact of CD3 stimulation
      on T cells.

PMID- 9916413
TI  - [Detection of enteroaggregative Escherichia coli from sporadic diarrhea
      patients].
AB  - A study of enteroaggregative Escherichia coli (EAggEC) which was recently
      reported as a causative agent of diarrhea was attempted, by isolating these
      organisms from the fecal samples collected from sporadic diarrhea patients in
      Miyazaki Prefecture during the period from January 1993 to April 1998, and by
      investigating several characteristics of the isolates. By using the PCR method
      targetting aggR gene which was a transcriptional activator of aggregative
      adherence fimbria I expression, thirty four strains of aggR(+)-Escherichia coli
      (E. coli) were detected from 2,652 fecal samples. Twenty nine of these 34
      isolates were confirmed as EAggEC by demonstration of aggregative adherence to
      HEp-2 cells, and the other 5 isolates were not EAggEC because they showed
      negative adherence to HEp-2 cells. The above mentioned, aggR-PCR method revealed
      that there were a few non-EAggEC strains with aggR gene. It has been reported
      that aggregative adherence fimbriae are encoded by the plasmid of about 60 Md.
      All of the 29 EAggEC isolates possessed plasmids of about 50 Md or more, and
      these plasmids were suggested to relate to aggregative adherence fimbriae.
      Sixteen (55%) of the 29 isolates were classified serologically into two
      serotypes, O111:H21 and O126:H27, and the other 13 isolates were classified into
      ten groups or more which included a few strains in a group. EAggEC heat-stable
      enterotoxin 1 (EAST1) gene was demonstrated in nineteen of 29 isolates. In drug
      susceptibility test, 72%, 59% and 21% of the 29 isolates showed resistance to
      Ampicillin, Cefazolin, and Streptomycin, respectively.

PMID- 9916414
TI  - [Prevalence of intestinal parasites among Japanese residents in developing
      countries].
AB  - We examined fecal specimens of Japanese residents in developing countries in
      order to know the prevalence of intestinal parasites in the group. One fecal
      specimen was collected from each 981 (in 1995) and 1275 (in 1996) Japanese living
      in Asia, the Middle East, Europe, Africa and Latin America. The specimens were
      fixed with 10% formalin in each area, and were examined in Japan by concentration
      method (formalin-ether sedimentation) to find protozoan cysts or helminth eggs.
      The infection rate of intestinal parasites was 3.0% in 1995 and 2.4% in 1996. The
      rate was high in Africa (1995: 5.7%, 1996: 4.7%) and Asia (1995: 3.8%, 1996:
      3.0%). Regarding to the species of the parasites, Giardia lamblia (17 cases),
      Trichuris trichiura (14) and Ascaris lumbricoides (11) were detected frequently.
      Additionally, 7 cases of Heterophyes heterophyes infection were found in Asia and
      the Middle East. The infection rate was higher in adults than that in children,
      and a positive relationship between the infection rate and duration of stay was
      observed. Among the Japanese infected with intestinal parasites, abdominal
      symptoms such as diarrhea or abdominal pain were common (36.8%). It is also
      noteworthy that 28.1% of the Japanese infected had a history of gastric diseases
      such as gastric ulcer. Although the infection rate of intestinal parasites among
      Japanese residents in developing countries was low, compared to that of the
      natives in the countries, the rate is still higher than that in Japanese living
      in the home country. It is necessary to continue preventive measures such as
      health education in order to eradicate intestinal parasitic infections from this
      group.

PMID- 9916415
TI  - [Current status of acute respiratory infections in children under five years of
      age in Nairobi, Kenya].
AB  - Two hundreds and twenty-six children under five years of age with pneumonia were
      recruited from an urban poor area in Nairobi, Kenya, and examined for pathogens
      for 1 year from February 1997. One hundred and twenty-eight of the 226 patients
      were pathogen-positive cases. The patients under 1-year-old were 61.8% of the
      pathogen-positive cases. A total 192 organisms were isolated from 128 pathogen
      positive patients. Streptococcus pneumoniae had the highest prevalence rate of
      31.3%, followed by respiratory syncytial virus with 10.4%, Candida albicans with
      9.9%, Moraxella (B) catarrhalis with 7.8%. In S. pneumoniae, 66.7% of the
      organism was resistant to oxacillin. It was also shown that 51.1% and 65.1% of
      the S. pneumoniae strains were resistant to gentamicin and trimethoprim/sulfam,
      respectively. From these results, it is clear that a lot of multi-drug resistant
      S. pneumoniae strains including penicillin-resistant S. pneumoniae were
      frequently detected in an urban poor area.

PMID- 9916416
TI  - [Evaluation of pyuria by means of urinary sediment method--a comparison to the
      counting chamber method].
AB  - We compared the urinary sediment method to counting chamber method in evaluating
      pyuria, in order to elucidate an issue of urinary sediment method. The KOVA
      system was used for counting chamber method. Three hundred and ten urine
      specimens from the patients who visited Fuji City Central Hospital in March,
      1995, were employed. The numbers of leukocytes of each specimen was counted by
      means of urinary sediment method and counting chamber method, and compared. The
      urinary leukocyte count evaluating by means of these two methods were correlated
      well. However, the discrepancy of urinary leukocyte counts by means of these two
      methods were recognized in two specimens. In these two specimens, the leukocyte
      count was 1 to 4/5HPF by means of urinary sediment method, but more than
      50/microliter by means of counting chamber methods. Significant bacteria (10(4)
      cfu/ml or more), positive esterse reaction, and high pH (8.5) were recognized in
      both specimens. In addition, one of two these specimens was hypotonic (specific
      gravity was 1.008). Therefore, it was suggested that leukocytes were sometimes
      disrupted with centrifugation. These results indicate that counting chamber
      method is more useful urinary sediment method to detect pyuria.

PMID- 9916417
TI  - [Estimation of probiotics by infection model of infant rabbit with
      enterohemorrhagic Escherichia coli O157:H7].
AB  - We examined the preventative effect against enterohemorrhagic Escherichia coli
      O157:H7 (EHEC) infection in rabbits on administration of probiotics contained in
      Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus. The
      probiotics were administered to 5 days old Japanese white rabbits throughout the
      experiment. Inoculation of 10(6) colony forming units (CFUs) of EHEC per rabbit
      was tried 8 days after birth. Three days after EHEC inoculation, in the control
      group (not administered probiotics), diarrhea was observed in approximately 80%
      of the rabbits, on the other hand, in the group administered probiotics, rabbits
      showed diarrhea in 15%. In necropsy, the number of EHEC in the contents of the
      cecum and the number of attaching and effacing (AE) lesions were fewer in the
      probiotics group than in the control group. These results suggest that infant
      rabbits are useful as a colitis model for EHEC, and the probiotics are effective
      for the prevention of the growth of EHEC in the intestine and for diarrhea.

PMID- 9916418
TI  - [A case with chronic active EB virus infection accompanied with pulmonary
      candidiasis].
AB  - A 44-year-old woman with a history of intermittent fever for several years was
      admitted because of burn on her leg. On admission, she had hepatosplenomegaly and
      fever. Antibiotic therapy was started for bacterial infection of the burn. She
      lost her appetite and IVH was started. During the treatment, high fever appeared
      and chest X-ray films showed multiple nodular infiltrates throughout both lung
      fields. Candida albicans was isolated from IVH catheter culture and pulmonary
      candidiasis was suspected. Her fever and lung involvements were successfully
      treated with fluconazole. During the course, serum anti-EB-VCA-IgG antibody
      persisted at a high titer and anti-EBNA antibody remained negative. EB virus DNA
      was detected in the peripheral blood and bone marrow. Thus, she was diagnosed as
      chronic active EB virus infection.

PMID- 9916419
TI  - [Two cases of spotted fever group rickettsiosis contracted in southern parts of
      Africa].
AB  - A 40-year-old Japanese male stayed in Zimbabwe and developed a fever above 38
      degrees C during which he noted a typical eschar in the lumbar region and also
      regional inguinal lymphadenopathy. Although not conspicuous, erythematous
      eruptions accompanied by itching were observed on the face, trunk and lower
      extremities. After returning to Japan and visiting our hospital, he was suspected
      of rickettsiosis and put on minocycline which gradually led to the improvement of
      the symptoms. Immunofluorescence antibody determinations disclosed rising titers
      against Rickettsia conorii (R. conorii) for both IgM and IgG classes. The second
      patient, a 34-year-old Japanese male, developed fever, generalized erythema and a
      typical eschar while staying in South Africa. The first blood sample showed
      positive IgM and IgG antibodies against R. conorii, and the second sample a
      decline in IgM but not in IgG class antibodies. Both cases were diagnosed as
      spotted fever group rickettsiosis based on their clinical manifestations
      including typical eschar and also the results of antibody determinations. Most of
      the previous cases of spotted fever group rickettsiosis in Africa have been
      regarded as Mediterranean spotted fever which is caused by R. conorii and
      transmitted by Rhipicephalus sanguineus. However, recently, the presence of
      another type of spotted fever group rickettsiosis, African tick-bite fever,
      caused by Rickettsia africae and transmitted by Amblyomma hebraeum has been
      proposed. Although clinical features of the two rickettsiosis are reported to be
      separable, apparent cross reaction between the two organisms hampers the use of
      conventional antibody determinations for their differentiation. For the two cases
      presented here identification of the causative rickettsia species was impossible,
      because they were not isolated. With ever increasing numbers of international
      travel, physicians should be alert to the possibility of spotted fever group
      rickettsiosis when encountering febrile patients returning from endemic
      countries. This is particularly important considering that beta-lactam
      antibiotics commonly used as an empiric therapy are not effective, and the
      disease has a potential to develop into severe forms.

PMID- 9916420
TI  - [A case of imported paratyphoid fever associated with Giardia lamblia and
      Isospora belli infection].
AB  - We report a case of imported paratyphoid fever associated with Giardia lamblia
      and Isospora belli infection. The patient was a 23-year-old Japanese female with
      complaints of high grade fever and diarrhea after 10 days traveling to Nepal.
      Salmonella Paratyphi A was isolated from the blood and fecal cultures on
      admission and Ciprofloxacin of 200 mg tid was administered for 14 days. Fecal
      examination revealed cysts of G. lamblia at the same time and metronidazole of
      250 mg tid for 7 days was effective for their eradication. During the follow-up
      studies oocysts of I. belli were found and cotrimoxazole of 960 mg bid for 10
      days was effective for their eradication. Fecal examinations on parasites which
      is rare in Japan such as I. belli are recommended to the cases returning from
      tropical areas.

PMID- 9916421
TI  - Hepatic candidiasis responding to a low-dose infusion of amphotericin B in a
      patient with acute leukemia.

PMID- 9916422
TI  - [Bacillus cereus septicemia in a patient with severe aplastic anemia].
AB  - A 78-year-old female was admitted with complaints of malaise and fatigue in the
      legs. The patient was diagnosed as severe aplastic anemia and treatment was
      started with metenolone and steroid pulse therapy. Administration of antibiotics
      and granulocyte-colony stimulating factor which led to a resolution of the high
      fever. About four months after admission, the patient developed vomiting and
      abdominal pain with a spiking fever. The next day after suddenly losing
      consciousness, she died. B. cereus was isolated from blood cultures. Autopsy
      specimens of the liver, cardiac muscle and lung showed changes due to B. cereus.
      This pathogen is widely distributed in nature. We should not overlook B. cereus
      as a contamination, but rather should consider it a potential pathogen in
      immunocompromised hosts, when it is isolated from blood cultures.

PMID- 9916423
TI  - [Detection of small round structured virus from oysters by RT-PCR].

PMID- 9916424
TI  - [Should desmoid fibromas be operated?].
AB  - The 30-year experience of P.A. Herzen Moscou Cancer Research Institute in the
      treatment of soft tissue desmoid fibromas (DF) is summarized. A comparative study
      of effectiveness of surgical, combined, radiation and medicamentous methods was
      carried out. Frequency of recurrences after surgical treatment made up 94%, after
      combined treatment with preoperative radiation it decreased 3-fold (27.5%), in
      cases of postoperative radiation it made up 53%, and after radiation therapy-
      15.7%. However radiation therapy may have limitations due to necessity for
      irradiation of large tumour masses and usage of high-dose ionized irradiation
      which results in development of postradiation tissue damages. Further research
      brought about an original chemohormonal therapy (tamoxiphen, vinblastin,
      methotrexate), which provides stable recovery in 81.3% of patients. Principal
      positions for management of DF are formulated.

PMID- 9916425
TI  - [Results of esophageal cancer surgical treatment in multiple primary neoplasms].
AB  - Available are the results of surgical treatment of 11 patients with cancer of the
      esophagus revealed metachronously through 6 months--3 years after treatment of
      oro-pharyngeolaryngeal cancer (5 patients) and diagnosed synchronously with
      cancer of the stomach (3 patients), the lung (2 patients) and leiomyoma of the
      esophagus (1 patient). Radical operations on the esophagus were performed in all
      the patients, in synchronous tumors they were one-stage surgical intervention.
      Postoperative complications such as pneumonia were observed in the majority of
      patients, who previously underwent radiation or combined treatment for laryngeal
      cancer, as well as in all patients, who were operated on the esophagus and the
      lung in one stage. The necessity of active bronchial sanation in pre- and
      postoperative period of patients after treatment of laryngeal cancer and
      advisability of two-stage surgical treatment of synchronous tumors of the
      esophagus and the lung, the operation for lung cancer being performed at the
      second stage of treatment, are stressed in conclusion. In synchronous involvement
      of the esophagus and the stomach one-stage intervention on these organs is the
      most advisable.

PMID- 9916426
TI  - [Multicomponent intravenous and epidural anesthesia in aorto-coronary bypass
      surgery].
AB  - The influence of epidural anesthesia (CEA) on clinical manifestations, cortisole
      and adrenocorticotropic hormone (ACTH) level, central hemodynamic values during
      aorto-coronary bypass surgery (ACBS) in 56 patients aged 42-68 years with
      preserved functional capacity of the myocardium was studied. Catheterisation of
      the epidural space was carried out in the evening before the operation according
      to the standard method at the level of T4-T5 with the use of disposable epidural
      set. During the procedure before perfusion 2% solution of lidocaine 3.8 +/- 0.2
      mg/kg was introduced in epidural space (taking into account test-dose) as a bolus
      in 3-4 motions. The dose of local anesthetics for infusion was selected
      separately for each individual case with due regard for hemodynamic values.
      During artificial circulation additionally local anesthetic was introduced as a
      bolus, the dose being 4.7 +/- 0.8 mg/kg. At the end of the operation morphine
      (0.061 +/- 0.001 mg/kg) was introduced. It was established that combined
      application of intravenous and epidural anesthesia represents highly effective
      method of anesthesia in aorto-coronary bypass surgery. According to clinical
      course data, cortisone and ACTH blood contents and hemodynamic parameters, EA
      provides adequate anesthesia, promotes stabilization of hemodynamic values and
      creates functionally more advantageous conditions for the myocardium in patients
      with CHD during aorto-coronary bypass operation. Anesthesiologic aid with the use
      of EA promotes reduction of intravenous anesthetics expenditure, earlier waking
      up of the patients in postoperative period and decrease in duration of
      postoperative artificial lung ventilation.

PMID- 9916427
TI  - [Combined treatment of aged patients with obliterative atherosclerosis of legs
      grade IV by intraarterial infusions and CO2-laser].
AB  - Analysis of combined treatment of aged patients with obliterative atherosclerosis
      of the vessels of low limbs grade IV by intraarterial infusions and CO2-laser
      showed good short-term results. The proposed method of "sparing surgery" is not
      much traumatic and simple in performance. It creates additional curative effect
      by improvement of regional circulation in ischemic area and by antibacterial
      stimulating action on tissues with trophic damages by CO2-laser, it diminishes
      operation risk and promotes favourable healing process.

PMID- 9916428
TI  - [Therapeutic effects of prolonged normovolemic hemodilution in patients with
      Raynaud's disease].
AB  - 51 patients with Raynaud's disease has undergone prolonged normovolemic
      hemodilution (PNH) with a good effect. Disappearance of painful syndrome in
      78.43% of cases, and a significant decrease of pains in 21.37% of cases was
      demonstrated. Complete healing of ulcero-necrotic defects of end phalanges of the
      hands was observed in 7 patients of 10 and partial--in 3. A significant remission
      of the disease in follow-up period was obtained. Thus, prolonged normovolemic
      hemodilution has resulted in significant improvement of short- and long-term
      results of treatment in patients with Raynaud's disease.

PMID- 9916429
TI  - [Some immunologic aspects in postoperative peritonitis].
AB  - Examination of blood serum and cellular elements of 45 patients with
      postoperative diffuse purulent peritonitis shows that in the majority of examined
      persons before and in the first days after the operation immunodepression exists.
      The dynamics of immunologic disturbances (antibody titers, phagocytosis,
      immunoglobulines, T- and B-lymphocytes) are sufficiently informative and as a
      rule, correlate with clinical course of peritonitis. Adequate reaction of the
      organism to infection resulted in a favourable outcome. Low values of immunologic
      indices in postoperative period necessitate the use of stimulant therapy in
      combined treatment of this complication.

PMID- 9916430
TI  - [Cholecystectomy from mini-laparotomy approach].
AB  - Mini-laparotomy 3-4 cm long at projection of hepatoduodenal ligament with the
      help of surgical set of the firm "SAN" (Ekaterinburg) makes it possible to carry
      out successfully cholecystectomy and manipulations on the choledochus with
      minimal operation trauma. 104 patients were operated on for acute chronic
      cholecystitis with the help of this method. Mini-laparotomy in cholecystectomy
      enables intraoperation cholangiography and manipulations on the choledochus in
      any conditions.

PMID- 9916431
TI  - [Minimally invasive transcutaneous interventions in elimination of suppurative
      residual cavities in liver after echinococcectomy].
AB  - The results of treatment of 34 patients with suppurative residual cavities in the
      liver (SRCL) after echinococcectomy are analyzed. New method of elimination of
      SRCL consisted in transcutaneous puncture and drainage of the infected cavity
      followed by transdrainage laser irradiation of its walls by Nitrogen UV laser and
      Helium-Neon laser of visible spectrum, was applied in 31 patients. Transdrainage
      irradiation was carried out at the background of daily procedures of
      transcutaneous laser radiation of the liver (Arsenid-Gallium infrared laser).
      Minimal traumatism of transcutaneous interventions and pronounced antibacterial,
      antiinflammatory and stimulating influence of low-energy lasers made it possible
      to improve significantly the results of treatment of SRCL patients.

PMID- 9916432
TI  - [Bandages with proteolytic enzymes in the treatment of purulent wounds].
AB  - Clinical trial of well-known and available in Russia enzyme-containing dressings
      (ECD): dalcex-tripsin and its modification--tripsin-chlorhexidin and tripsin urea
      containing, profezim, sipralin, lysosorb, collavin and teralgim. The most
      effective ECD for cleansing of festered wounds, burns and trophyc ulcers are
      collavin and lysosorb (application wound draining sorbents from helevin and
      proteolytic enzymes--collagenase of crab and terrylytin, respectively). Combined
      usage of sorbents and antiseptics substantially increases their curative
      properties. The other ECD have some shortcomings (low sorption and draining)
      which makes it possible to recommend them at present time only for limited usage.
      Draining sorbents and their combinations hold promise for field surgery, pyogenic
      traumatology, combustiology, cryopathology, gynecology, otolaryngology,
      neurosurgery, dermatology.

PMID- 9916434
TI  - [Sternal osteomyelitis].
AB  - The authors present data based on the analysis of diagnosis and treatment of 11
      patients with sternal osteomyelitis which in 9 patients was of traumatic origin
      and in 2 was hematogenous. Early diagnosis is difficult. Clinical manifestations
      and roentgenography of the sternum are essential for diagnosis. In combined
      treatment of osteomyelitis preference is given to radical removal of
      osteomyelitic masses within healthy tissues with tamponade of the residual osteal
      cavity by local tissues.

PMID- 9916435
TI  - [Prophylaxis of purulent complications in operations on large joints by
      endolymphatic infusion of drugs].
AB  - 2 groups of patients operated on knee joints for traumatic injuries were
      examined. In the study group endolymphatic drug therapy was carried out in
      postoperative period, in control group of patients conventional way of
      intramuscular administration of preparations was used. During the treatment,
      plasmatic cells, macrophages and tissue basophiles in synovial liquor were
      studied as well as synthesis of nucleic acids (DNA and RNA) in plasmatic cells.
      It was shown that immune homeostasis of synovial liquor in postoperative period
      normalized faster in endolymphatic administration. The studies of tissue
      basophiles have shown that inflammatory process in the knee joint is completed
      faster when endolymphatic route of drug administration was used. Clinical results
      evidence of higher effectiveness of endolymphatic therapy in comparison with
      conventional method of treatment in postoperative period. In the former case the
      inflammatory process was completed by the 5th day, in the latter--by the 7th-9th
      day. The endolymphatic therapy in all the patients resulted in healing of
      operation wounds by primary intention. In the group of patients treated by
      standard methods, suppuration of the wound was detected in 6 from 27 patients and
      postoperative synovitis in 7-9 days was observed in 6 patients.

PMID- 9916433
TI  - [Use of serotonin for treatment of patients with diabetic angiopathies].
AB  - In 26 patients (female 11, males--15) with diabetic angiopathy (necrosis of the
      foot or toes) local measurement of pO2 by transcutaneous mode was carried out
      before and during introduction of serotonine adipinate. Simultaneously with
      evaluation of pO2 in 14 patients electromyography (EMG) was made. Serotonine
      adipinate was introduced intravenously with a speed of 5.0-10.0 mg per hour. In
      this group mean age of the patients made up 57.4 years, mean values of initial
      pO2 25.6 mm Hg, and mean indices of pO2 at the moment of serotonine treatment
      38.5 mm Hg. Average increase of pO2 during serotonine infusion was registered as
      50.4% in comparison with mean initial data. In all 14 patients, who underwent
      simultaneous measurement of pO2 and registration of EMG, reinforcement of
      electrical activity of smooth muscles (SM) of various intensity and increase in
      tissue pO2 were detected. Improvement of microcirculation (increase of
      transcutaneous pO2, reinforcement of electrical activity of SM as a result of
      serotonine introduction) evidences that functional and morphological changes of
      serotonine receptors of SM are involead in genesis of diabetic angiopathy. The
      data obtained showed that in diabetes mellitus, besides insulin deficiency,
      insufficiency of such an endogenous factor as serotonine duclops. Thus, serotonin
      should be used for prophylaxis and treatment of diabetic angiopathies.

PMID- 9916436
TI  - [Antibacterial therapy in pyo-sepsis complications of patients in intensive care
      units].
AB  - One of the most actual problems of contemporary intensive care service is
      analysed. It is antibacterial therapy of patients with generalized pyo-septical
      complications (PSC) who underwent critical conditions. 157 patients with severe
      combined trauma, massive hemorrhage and after extended and traumatic operations
      were examined and treated. Bacteriological monitoring was carried out, condition
      of opsonophagocytic system of patients immunity was assessed, and dynamics of
      clinical symptoms was evaluated. The scheme of antibacterial treatment of
      patients with PSC was developed depending on the terms of illness, location of
      the focus and pathogene of pyoseptical process which provided lowering of
      mortality rate in patients of intensive care profile.

PMID- 9916437
TI  - [Modification of method for determination of medium-molecular peptides and its
      application in pediatric surgery].
AB  - Taking into account clinical significance of determination of medium-molecular
      peptides' concentration in various surgical diseases and limitation of blood
      sampling in children, modification of the method for determination of medium
      molecular peptides in blood serum is proposed, which requires 0.1 ml of serum and
      is based on deproteinization of cooled ethanol followed by spectrophotometry of
      peptide solution at 210 nm. Comparison study of the results of examination by
      this method and routine one was carried out. Specificity and advantages of the
      suggested modification are discussed.

PMID- 9916438
TI  - [Penetrating gunshot wound of left heart ventricle].

PMID- 9916439
TI  - [Uncommon cause of acute intestinal obstruction].

PMID- 9916440
TI  - [Simultaneous laparoscopic operation].

PMID- 9916441
TI  - [One-stage resection of stomach, cecum and sigmoid colon for multiple primary
      neoplasms].

PMID- 9916442
TI  - [Lipid pancreonecrosis combined with gestosis of grave stage in birth giving
      woman].

PMID- 9916444
TI  - [Calendar of memorable dates in the history of surgery for 1999].

PMID- 9916443
TI  - [Acute venous thrombosis: new directions in prophylaxis and treatment].

PMID- 9916445
TI  - [Assessment of effects of lead on humans].
AB  - The author summarizes materials published in the issue, stresses importance of
      "Lead and Human Health" problem and necessitates further research on disclosing
      the lead influence on humans, with consideration of possible sources (air,
      waters, foods). Important matters also are improvement of hygienic regulation,
      biologic monitoring methods, environmental protection means; epidemiologic
      research covering large samples of workers, general population and children.

PMID- 9916446
TI  - [Results of the Sanitary and Epidemiologic Service studies on the effects of lead
      on health status of workers].
AB  - The article covers through studies concerning causes of environmental pollution
      and workers' health state in order to specify prophylactic measures.

PMID- 9916447
TI  - [Several aspects of occupational effects of lead compounds on the cardiovascular
      system].
AB  - The article covers some results of complex sanitary, hygienic, clinical,
      functional and laboratory examinations of individuals working in main shops of
      storage battery production where lead and its inorganic compounds are principal
      occupational hazards. Lead and its compounds harm human health, being risk
      factors for vegetoneurosis and arterial hypertension. Hemodynamic studies using
      integral rheography revealed hemodynamic type of circulation, increase of general
      and peripheral vascular tone. The main causes of hemodynamic disorders are
      influence of lead compounds on autonomous nervous system, prevalence of the
      parasympathetic section and metabolic disorders in myocardium.

PMID- 9916448
TI  - [Biologic monitoring of the health status of workers exposed to lead].
AB  - Use of biologic monitoring for workers exposed to lead is the most efficient
      means preventing lead intoxication all over the world. Considering WHO
      recommendations and personal research, the authors specified national system of
      biologic monitoring for workers exposed to lead. The system covers mandatory
      control of serum and urinary lead levels. The authors based biologic MAC for lead
      in serum-50 mg/dl (males) and 30 mg/dl (females).

PMID- 9916449
TI  - [Importance of hygienic monitoring in detection of etiological mechanisms of
      chronic lead poisoning in battery production plants].
AB  - The authors demonstrate importance of hygienic monitoring for describing the
      course of chronic lead intoxication among workers of storage battery production.
      The authors specify and describe the principles of hygienic monitoring program,
      grouped and individual parameters (hygienic, medical and biologic) that are risk
      factors for chronic lead intoxication and subjects of control. The article
      contains some examples demonstrating possibilities of hygienic monitoring for
      matching the occupational morbidity parameters of storage battery production
      workers with work conditions and other parameters influencing the disease.

PMID- 9916450
TI  - [Materials for adjusting MAC of lead in the workplace air].
AB  - The authors present materials of clinical and hygienic study checking MAC for
      lead in the air of workplace. The study covered 506 workers of printing,
      nonferrous metallurgy plants and storage battery production. The study included
      examination of cardiovascular, nervous, digestive systems and laboratory values
      and revealed high diagnostic value of serum lead level and low one of urinary
      lead level. High number of the groups examined and mathematical processing of
      incomplete selects (Caplan--Meyer assess) proved that intoxication resulted from
      higher lead concentrations (0.58-0.8 mg/m3). The lead levels of 0.2 mg/m3 in
      23.7% of cases induced changes of 2-3 laboratory values-first signs of lead
      intoxication--and in 5.2% of cases some symptoms of vegetative sensory
      polyneuropathy were seen. These lead levels are therefore determined as minimally
      acting. Calculations of probability parameters for health risk helped to set MAC
      for lead in the air of workplace at 0.05 mg/m3 (this value is accepted by Russian
      Health Ministry) with mandatory control of serum lead level.

PMID- 9916451
TI  - [Experience in the study of the effects of lead on the health status of children
      in Belovo].
AB  - Lead releases in Belovo town containing metallurgy enterprise had reached 120
      tons/year earlier, but in recent years have decreased to 9 tons/year. Reduction
      of the production induced decrease of lead levels in the ambient air from 0.7-2.3
      mg/m3 in 1994 to 0.001-0.24 mg/m3. Lead concentration in the soil ranges from 30
      to 3000 mg/kg. Lead levels were measured in serum of 91 children, in hair of 67
      ones and in teeth of 15 children. Serum lead levels in children aged 7-8 years
      varied from 0.5 to 39 mg/dl, with an average of 9.9 mg/dl (SD is 5.2 mg/dl),
      geometric mean is 8.5 mg/dl and error of geometric mean is 3.3. 46% of the
      children had serum lead levels exceeding the normal one (10 mg/dl). Average lead
      level in the hair equaled 4.5 mg/g (SD is 4.9 mg/g). The children living in towns
      with higher environmental lead levels demonstrated more frequent anxiety and
      changes in higher psychic functions. The major points influencing the serum lead
      level are proximity to highway, dietary load of goods grown near the residence,
      mother's smoking. Biokinetic model describing lead transfer into the blood helped
      to evaluate various modes of the enterprise functioning and efficiency of some
      environmental protection measures. The most efficient are measures aimed to lower
      dietary intake of lead, less efficiency is associated with measures reducing lead
      levels in air, dust and soil.

PMID- 9916452
TI  - [Evaluation of hazards caused by effects of lead on preschool children living
      near a copper-smelting plant].
AB  - The studies conducted in Krasnouralsk (Sverdlovsk region) proved that
      environmental pollution with lead in the area subjected to releases by copper
      melting enterprise creates significant risk of lead accumulation in preschoolers
      especially prone to unfavorable factors. Considering various environmental lead
      sources, biokinetic analog formation reliably forecasts serum lead levels. Soil
      polluted with lead, as the analog considers, is the most important environmental
      lead source. The authors suggest a system of prophylactic measures based on
      analysis of children's health risk caused by environmental pollution with lead.

PMID- 9916453
TI  - [Detection of lead in environmental objects and biologic materials during
      monitoring].
AB  - The authors specified methods to detect lead in biologic materials. The quality
      control covered use of Russian and foreign standard samples, the results proved
      to agree. Lead was detected by AAS technique (direct and flow-type variants with
      preliminary concentration of lead) and ELRA method. The authors determined
      measurement limits sufficient for analysis of complex biologic materials. The
      measurement range for lead varied from 0.002 mg/kg (plants) to 3,000 mg/kg
      (soil); the range of serum lead levels was < 0.5-39 mg/dl.

PMID- 9916454
TI  - [International conference on environmental lead pollution in Russia (Moscow,
      April 2, 1998)].

PMID- 9916455
TI  - [Some novelties in the prevention and treatment of certain occupational
      diseases].

PMID- 9916456
TI  - Ribosomal genes of Histoplasma capsulatum var. duboisii and var. farciminosum.
AB  - A total of 1704 basepairs of the 18S rDNA of Histoplasma capsulatum var. duboisii
      (HCD, strain CBS175.57) and H. capsulatum var. farciminosum (HCF, strain
      CBS478.64) were sequenced (EMBL accession no. Z75306 and no. Z75307). The 18S
      rDNA of HCD was 100% identical to a published sequence of H. capsulatum var.
      capsulatum (HCC). The 18S rDNA of HCF showed one transversional point mutation at
      the nucleotide position 114 (ref. Saccharomyces cerevisiae). Hybridization
      confirmed that, in the 18S rDNA of two out of five strains of HCF, guanine was
      substituted for cytosine at the nucleotide position 114. Furthermore, identical
      group 1C1 introns (403 bp) were found to be inserted after position 1165 in four
      out of five strains of HCF, including the two strains with point mutations in the
      18S rDNA, and a slightly different group 1C1 intron (408 bp) was detected in one
      strain of HCC without this point mutation. Intraspecific sequence variability in
      the highly conserved 18S rDNA because of occurrence of introns and mutations as a
      possible source of error in molecular diagnostics is discussed. In addition,
      internal transcribed spacer regions between the 18S rDNA and the 5.8S rDNA (ITS1)
      of three strains of HCF, and one strain each of HCC and HCD showed significant
      sequence variability between varieties and strains of H. capsulatum.

PMID- 9916457
TI  - African histoplasmosis: report of two patients treated with amphotericin B and
      ketoconazole.
AB  - Two patients with African histoplasmosis manifested by ulcers and cutaneous
      swellings are described. The inguinal lymph nodes were also involved in one
      patient. Treatment with amphotericin B combined with ketoconazole was successful.

PMID- 9916458
TI  - Rhinocerebral zygomycosis following bone marrow transplantation in chronic
      myelogenous leukaemia. Report of a case and review of the literature.
AB  - We report on a man suffering from chronic myelogenous leukaemia treated by
      allogeneic bone marrow transplantation who, in the late post-transplantation
      phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The
      origin of the ascending infection was the sinus sphenoidalis from which fungal
      hyphae spread to the central nervous system via the skull and the dura mater. The
      first symptoms of this severe infection were cerebral convulsions and a bilateral
      total amaurosis. The isolation of the pathogen from post mortem tissue was not
      successful. The present case is compared with previous reports of zygomycoses
      after bone marrow transplantation.

PMID- 9916459
TI  - False-positive results in premature infants with the Platelia Aspergillus
      sandwich enzyme-linked immunosorbent assay.
AB  - The sensitivity of a sandwich enzyme-linked immunosorbent assay (ELISA) for
      detecting Aspergillus galactomannan was tested using 783 serum samples obtained
      from 247 patients (1-15 sera per patient) with severe underlying diseases
      (haematological malignancies or intensive care unit stay). We selected 146 serum
      samples from 50 patients for retesting. Serum samples were frozen after routine
      testing at -18 degrees C until retesting. All patients charts were checked for
      signs of Aspergillus infection, such as pneumonia or sinusitis. Adult patients
      were divided into four groups: proven (5), probable (6), suspected (8) or
      unlikely (25) Aspergillus infection. The results of Platelia ELISA were 100% in
      proven, 33% in probable and 50% in suspected Aspergillus infection. Patients with
      unlikely infection had no positive results with Platelia ELISA. Group 5 consists
      of six paediatric patients with prolonged ICU stay and a birth weight of 400-1320
      g. In five out of six infants we found positive results with Platelia ELISA. All
      positive results in this group of patients are considered as false positive
      (83.3%).

PMID- 9916460
TI  - Cutaneous purulent aspergillosis in a young man with chronic granulomatous
      disease.
AB  - We describe a case of cutaneous purulent aspergillosis in a 19-year-old man with
      chronic granulomatous disease (CGD) treated successfully with a 6-month regimen
      of itraconazole. The therapeutic effect of the drug was seen after 1 month of
      administration. Surgical treatment of the skin lesions, although first planned,
      was not necessary.

PMID- 9916461
TI  - Airborne fungi and their secondary metabolites in working places in a compost
      facility.
AB  - The present study investigates in detail the exposure to airborne fungal spores
      in working places in compost facilities. The fungal species composition in the
      air is compared with the spectrum of microbial metabolites with regard to the
      physiological properties of different fungal species. The results indicate that
      the spectrum of microbial volatile organic compounds (MVOCs) and the production
      of mycotoxins can be specific for certain species. In addition to the pathogenic
      and allergological relevance, the fungi may have different toxicological health
      impacts.

PMID- 9916462
TI  - Phenotypic and genotypic differentiation of several human and avian isolates of
      Cryptococcus neoformans.
AB  - The Cryptococcus neoformans strains isolated from two human cases could be
      diagnosed as Cr. neoformans var. neoformans by differentiation on the basis of
      their characteristics determined by proline, canavanine and EDTA urease tests.
      The results of the serovar assignment were: for the isolate from the
      meningoencephalitis patient with lethal outcome, serovar A; for the strain
      isolated from the osteomyelitis patient with benign course, serovar D. Also, the
      PCR fingerprinting using primers (GACA)4, (CAC)5 and FM 1 resulted in a clear and
      reproducible assignment of the Cr. neoformans strains to the varieties neoformans
      and gattii, respectively, and, in addition, it confirmed the serovar assignment.
      No statistically confirmed differences in virulence between the osteomyelitis and
      the meningoencephalitis strain could be established by i.v. testing in mice, nor
      did the PCR with several primers provide any clues to a genetically determined
      higher virulence of the meningoencephalitis strain. The different classification
      as serovars A and D does not allow any conclusions concerning different
      virulence. It was not possible to retrospectively establish the sources of
      infection of the two Cr. neoformans infections, but pigeon faeces may well have
      played a role as a reservoir for one of the illnesses.

PMID- 9916463
TI  - Typing of Candida albicans and Candida parapsilosis: species-related limitations
      of electrophoretic karyotyping and restriction endonuclease analysis of genomic
      DNA.
AB  - Species-related discrimination limits of electrophoretic karyotyping (EK) and
      restriction endonuclease analysis of genomic DNA (REAG), using pulse-field gel
      electrophoresis, in typing Candida albicans (CA) and Candida parapsilosis (CP)
      were compared. Eleven CA and 12 CP isolates from individual neonates and three CA
      and three CP control isolates were used. For CA, EK and REAG with sfiI displayed
      seven and six banding-patterns, respectively. One karyotype and two SfiI banding
      patterns were observed among the control-isolates. Combining EK/REAG (SfiI)
      demonstrated nine composites and three distinct control-composites. For CP, EK
      displayed nine karyotypes, REAG (SfiI) demonstrated four banding-patterns, and
      REAG (BssHII) yielded six banding-patterns. EK and REAG/SfiI failed to
      distinguish any CP-controls whereas REAG/BssHII distinguished 2/3 CP-controls.
      Combining EK/REAG (SfiI) showed 10 composites indistinguishable from CP-controls
      whereas EK/REAG (BssHII) demonstrated 11 composites and three distinct control
      composites. These results illustrate that singly, EK and REAG have significant
      limitation in typing Candida species though EK is more precise. Combining both
      methods yields better results but the appropriate restriction endonuclease may
      vary by strains or species. These findings underscore the importance of combining
      multiple typing methods, testing several control isolates, and correlating the
      results with careful epidemiological assessment.

PMID- 9916464
TI  - Antisporulating and respiration-inhibitory effects of essential oils on
      filamentous fungi.
AB  - Sporulation of four species of filamentous fungi, namely Aspergillus fumigatus,
      Fusarium solani, Penicillium expansum and Rhizopus oryzae, was suppressed by
      gaseous contact with citron, lavender and thyme oils and, to a lesser extent, by
      that of perilla and tea tree oils. Lemongrass and cinnamon bark oils were
      scarcely active. The antisporulating effect of the essential oils was not
      observed when they were applied as a solution, indicating that their vapours were
      the active form. Moreover, exposure of fungal cultures to vapours of the active
      essential oils caused curling of the tips of aerial hyphae (R. oryzae) or
      incomplete development of conidiophores (A. fumigatus). These antisporulating
      effects of the vapourizing essential oils seemed to be correlated with their
      respiration-inhibitory activity, rather than with their growth-inhibitory
      activity.

PMID- 9916465
TI  - Study of the action of alpha-hederin on the ultrastructure of Candida albicans.
AB  - alpha-Hederin, a saponin isolated from Hedera helix (L.) (Araliaceae), was tested
      on Candida albicans ultrastructure. The concentrations used were 6.25, 12.5, and
      25 micrograms ml-1 for an exposure time of 24 h. Transmission electron microscopy
      observations indicated that compared with untreated control yeasts, alpha-hederin
      induced modifications of cellular contents and alterations of cell envelope with
      degradation and death of the yeasts. The impact of alpha-hederin on the
      biomembranes and in particular on the plasmalemma is discussed. The antifungal
      activity of alpha-hederin was confirmed, as was the minimal inhibitory
      concentration (25 micrograms ml-1).

PMID- 9916466
TI  - Disseminated candidosis in premature twins.
AB  - A unique case of disseminated candidosis in premature twins is presented where
      twin A developed disease soon after birth and died prior to the administration of
      antifungal therapy. On the other hand, twin B developed infection on the 26th day
      of birth but survived, though with sequelae (hydrocephalus), since he was
      promptly and accurately diagnosed and treated.

PMID- 9916467
TI  - Fluconazole prophylaxis in patients with head and neck tumours undergoing
      radiation and radiochemotherapy.
AB  - The aim of the present study was to investigate the incidence of Candida
      stomatitis and resulting interruptions in radiation and radiochemotherapy in 50
      patients suffering from squamous cell carcinomas of the head and neck region
      receiving fluconazole (100 mg d-1) in comparison with a historical control group
      (n = 50) without specific prophylaxis. Twenty of the control patients (40%)
      demonstrated Candida stomatitis, with seven of them (14%) requiring interruptions
      in anticancer therapy. In contrast, none of the patients with fluconazole had
      evidence of Candida stomatitis (P = 0.0000051) and subsequent interruption of
      anti-cancer therapy (P = 0.0061). Laboratory monitoring for the presence of
      Candida species was performed in 30 patients before and after therapy with
      fluconazole. Candida albicans was identified less frequently after therapy when
      compared with the pretreatment status. However, C. glabrata and C. krusei were
      isolated in some of the patients, probably because of drug resistance of these
      subspecies. The results demonstrate the clinical usefulness of prophylactic
      fluconazole applications in patients suffering from head and neck tumours with
      the aim of reducing Candida stomatitis and the resulting interruptions in
      radiation and radiochemotherapy.

PMID- 9916468
TI  - Infection of an intravenous port system with Metschnikowia pulcherrima Pitt et
      Miller.
AB  - A patient with short bowel syndrome as a consequence of multiple intestinal
      resections for Crohn's disease, had a port system implanted to improve her
      nutritional status. One year later she presented with fever, weakness and
      nighttime sweating. Metschnikowia pulcherrima Pitt et Miller was grown in blood
      cultures from the port system. After antifungal chemotherapy using fluconazole
      and removal of the implant, the patient's condition improved markedly and her
      fever and sweating disappeared. We conclude that Metschnikowia pulcherrima can
      turn into a human pathogen in patients with indwelling catheters for parenteral
      nutrition. Chemotherapy with fluconazole and, whenever possible, removal of the
      implant, appear to be adequate treatment.

PMID- 9916469
TI  - Blastoschizomyces capitatus infection after contamination of fluids for
      intravenous application.
AB  - A six-month-old child died after infusion of fluids containing Blastoschizomyces
      capitatus. This represents a fatality due to this organism in a human with no
      proven immunosuppression.

PMID- 9916470
TI  - Echinococcosis with concurrent phaeohyphomycosis.
AB  - A double infection in the same organ, echinococcosis associated with
      phaeohyphomycosis in the lungs, is reported.

PMID- 9916471
TI  - Cerebral phaeohyphomycosis: report of a case from Nigeria.
AB  - A fatal case of cerebral phaeohyphomycosis in a 45-year-old Nigerian woman is
      described. The main clinical features were loss of vision, constant severe
      headache and the presence of a tumorous mass in the brain as detected on
      operation. Histology revealed granulomatous tissue reaction with fungal elements
      suggestive of Xylohypha bantiana.

PMID- 9916473
TI  - Tinea barbae due to Trichophyton mentagrophytes related to persistent child
      infection.
AB  - The case of a 42-year-old father is presented with 6 weeks' history of a painful
      kerion-like sycosis barbae. His two children had suffered from tinea manus 3
      months previously, also caused by the zoophilic fungus Trichophyton
      mentagrophytes probably acquired from guinea-pigs. Seemingly ignoring the
      pathogenetic link, oral antibacterial treatment had been the first therapeutic
      attempt initiated by the family physician. Finally, successful treatment was
      performed by means of oral application of fluconazole 50 mg daily for a period of
      6 weeks.

PMID- 9916472
TI  - Skin and nail infections due to Fusarium oxysporum in Tuscany, Italy.
AB  - Nine cases of skin and nail infection due to Fusarium oxysporum, diagnosed in
      Tuscany in the period 1985-97, are described. Two manifested as interdigital
      intertrigo of the feet and seven as onychomycosis. All were diagnosed on the
      basis of repeated mycological examination, direct microscope observation and
      culture, as well as histological examination of biopsy specimens in two cases of
      intertrigo. Fragments of the fungal colonies were examined by scanning electron
      microscopy (SEM) for more detailed observation of fungal morphology. All patients
      had normal immune status and a history of the infection extending several years.
      Four of the patients with onychomycosis were treated with oral itraconazole, and
      clinical and mycological recovery was achieved in three cases. Two others were
      treated with cyclopyrox nail lacquer, successfully in one case. One patient with
      intertrigo was treated with oral itraconazole and one with oral terbinafine; both
      were also treated and with topical drugs, however clinical recovery was not
      confirmed by the mycological results.

PMID- 9916474
TI  - [The role of intercellular adhesion molecule-1 in respiratory disorders].
AB  - Inflammatory processes are a key event in various respiratory disorders. Adhesion
      to microvascular endothelial cells is essential for the migration of leukocytes
      into inflamed tissues. Intercellular adhesion molecule-1 (ICAM-1) is a member of
      the immunoglobulin superfamily and a ligand for lymphocyte function-associated
      antigen-1 alpha (LFA-1 alpha). It has been shown to be required for leukocyte
      migration into inflamed tissues, and to play a significant role in inflammatory
      diseases, including rhinovirus infections. Clinical and experimental
      investigations have demonstrated a close relationship between the ICAM-1/LFA-1
      alpha pathway and the pathogenesis of asthmatic responses and acute respiratory
      distress syndrome. Further progress in research on the antagonism of ICAM-1 and
      LFA-1 alpha may provide new therapeutic approaches to inflammatory lung diseases.

PMID- 9916475
TI  - [A computed tomography-based study of features developmental patterns:
      Mycobacterium avium complex without predisposing conditions].
AB  - The aim of this study was to determine the computed tomographic (CT) features and
      developmental patterns of Mycobacterium avium complex disease (MAC disease). The
      author examined chest CT films from 36 cases of MAC without predisposing
      conditions, 8 early-stage cases, and 6 long-term follow-up cases. Prominent CT
      features included centrilobular abnormalities (in the lower part of the right
      upper lobe, middle lobe, and lingula predominance), airspace consolidation, and
      bronchiectasis in the middle lobe and lingula. Patterns of development typically
      began with centrilobular abnormalities in the lower part of the right upper lobe,
      middle lobe, or lingula. These centrilobular abnormalities tended to fuse,
      leading to airspace consolidation in the middle lobe and lingula. Bronchial wall
      thickening was followed by bronchiectasis in the middle lobe and lingula. These
      CT-image features and patterns (centrilobular abnormalities, airspace
      consolidation, and bronchiectasis) were thought to be manifestations of
      sequential phases of MAC disease development.

PMID- 9916476
TI  - [Survival and pulmonary hemodynamics in patients with sequelae of pulmonary
      tuberculosis who received antituberculosis chemotherapy and home oxygen therapy].
AB  - To date, the pulmonary hemodynamics of patients with sequelae of pulmonary
      tuberculosis have usually been examined as a unified set of criteria regardless
      of the treatments that patients undergo. Attracted by this subject, we studied
      the cerrelations between survival and pulmonary hemodynamics in patients with
      sequelae of pulmonary tuberculosis who were treated with antituberculosis drugs
      and home oxygen therapy (HOT). Our study examined 21 patients with a mean ages of
      58.0 years, mean PaO2 of 59.3 +/- 11.4 mm Hg, and mean PaCO2 of 51.9 +/- 6.3 mm
      Hg. In pulmonary function tests, mean % VC was 44.1 +/- 16.3%, and mean FEV 1%,
      66.6 +/- 23.0%. Twenty of the patients were given a diagnosis of pulmonary
      hypertension. Eighteen of the patients received HOT; as a group, their 3-year
      survival rate was 62.6%, which was not statistically significant compared to
      survival observed in post Japanese studies. Among the HOT patients, blood gases
      and pulmonary hemodynamics did not vary significantly between those who died
      within 2 years after right heart catheterization (short-term survivors) and those
      who lived for more than 5 years (long-term survivors). However, VC, % VC, and FVC
      values were significantly lower in the short-term survivors than in the long-term
      survivors. In conclusion, these findings revealed no statistically significant,
      differences compared with the data from past studies. Although pulmonary
      hypertension is associated with the poor prognosis for chronic obstructive
      pulmonary tuberculosis patients, in the patients we studied, the principle
      prognostic determinant was the seriousness of the restrictive ventilatory
      impairment, not pulmonary hypertension.

PMID- 9916477
TI  - [Effects of long-term preoperative administration of low-dose erythromycin on
      warm ischemia-reperfusion pulmonary injury].
AB  - The effects of long-term preoperative administration of low-dose erythromycin
      (EM) were experimentally examined in relation to the treatment of reperfusion
      disorders following pulmonary thermal ischemia. EM was administered at a dose of
      100 mg/day for 1 month to adult mongrel dogs with an average weight of about 12
      kg (EM group). A control group that did not receive EM was also enrolled. Using a
      pulmonary autograft model, collapse-thermal ischemia of the lungs was performed
      on each animal for 60 minutes. In the early stage of reperfusion, the following
      measurements were assessed: gas-exchange potency in the left lung, hemodynamics,
      water content, adhesion of neutrophils to vascular endothelium, and concentration
      of blood eicosanoids. The results for the 2 groups were then compared. In the
      control group, the blood level of leukotriene B4 (LTB4) increased shortly after
      reperfusion, neutrophils migrated toward the vascular endothelium and adhered to
      it, and pulmonary edema developed after 1 hour. However in the EM group, the
      blood level of thromboxane B2 was significantly suppressed before and after hilar
      stripping, and the increase in the blood LTB4 level and the migration of
      neutrophils shortly after reperfusion in thermal ischemia were suppressed.
      Eventually alleviation of pulmonary edema was indicated and significantly
      improved gas exchange was maintained. In conclusion, pulmonary injury during
      detachment of the hilum of the lung, as well as warm ischemia-reperfusion
      pulmonary injury, may be alleviated by preoperative administration of low-dose EM
      on a long-term basis.

PMID- 9916478
TI  - [Screening of sleep apnea/hypopnea syndrome by home pulse oximetry].
AB  - We evaluated the diagnostic accuracy and reproducibility of results obtained by
      home oximetry for the screening of sleep apnea/hypopnea syndrome. Our subjects
      were 40 patients who underwent home oximetry (12 patients for 1 night, 28
      patients for 2 nights) followed by all-night polysomnography. Their mean age was
      50.7 +/- 11.2 years; mean body mass index (BMI), 27.6 +/- 4.4 kg/m2; and mean
      apnea/hypopnea index (AHI), 36.0 +/- 26.0 hr-1. The data obtained by home pulse
      oximetry were fed into a personal computer, and utilized to calculate the
      desaturation cycles per hour (oxygen desaturation index (ODI) of 2-4%) and the
      percentage of time that SpO2 measured less than 90% (T 90). Polysomnography was
      used to monitor the number of apnea and hypopnea episodes per hour of sleep
      (AHI). With sleep apnea/hypopnea syndrome defined as AHI > or = 15, the
      diagnostic sensitivity and specificity of home pulse oximetry were 73.5% and
      83.3%, respectively, when ODI-3 > or = 15 was used as the diagnostic standard.
      Patients who showed false negative results had a lower mean BMI (25.5 +/- 3.0)
      than those who showed true positive results (28.8 +/- 4.6). The reproducibility
      of ODI-3 data obtained at home was very high (r = 0.964, n = 28). In conclusion,
      home pulse oximetry seems to be a very useful tool for the detection of
      apnea/hypopnea syndrome, but false negative results should be considered a
      possibility, especially in patients who are not obese.

PMID- 9916479
TI  - [Utility of the bronchoalveolar lavage procedure for the diagnosis of fat emboli
      syndrome (FES)].
AB  - In this study, we divided patients who were admitted to the Life Saving Center of
      our hospital with traumatic fractures into 3 groups: group F, including patients
      who were given diagnoses of FES according to Tsuruta's criteria; group K,
      including patients whose fractures resolved without any complications; and group
      KH, consisting of patients with fractures and pulmonary contusions. Broncho
      alveolar lavage (BAL) was found to be useful for detecting FES in these groups.
      The subjects studied were 45 patients with traumatic fractures who were admitted
      to the Life Saving Center of our hospital and who underwent BAL procedures
      between April 1989 and March 1997 (group F : 14, group K : 17, group KH : 14)
      After noninvasive treatment, all patients received their first BAL by
      bronchoscopy within 48 hours of admission. Significant differences distinguished
      group F from groups K and KH in terms of features of BAL washout solution, total
      cell count, and values for lymphatic subsets, P-III-P, LTB 4, and granulocyte
      elastase. Based on these results, it was concluded that BAL is useful for
      detecting FES and differentiating patients in group S from those in groups K and
      KH.

PMID- 9916481
TI  - [Current trends and problems in disclosure to lung cancer patients].
AB  - To assess current trends in the disclosure of cancer, we studied patients with
      primary lung cancer. Ninety-nine of 101 surgical patients (98.0%) and 96 of 128
      non-surgical patients (75.0%) had been informed of their illness. Family members
      of 2 surgical patients refused to allow disclosure due to concerns about mental
      intolerance. Reasons for non-disclosure to non-surgical patients ranged from
      rejection by family members (29 patients) to a lack of ability to understand (3
      patients). No mental problems were observed after disclosure. All but 11 patients
      were informed of their cancers by their physicians. Decisions regarding
      disclosure were not related to the pathological type or clinical stage of the
      cancer. For example, small cell carcinoma did not influence methods of or
      decisions concerning disclosure. Among non-surgical patients, the frequency of
      disclosure decreased with aging. However, no clear-cut factor appeared to
      influence the disclosure of metastatic sites. Views about informed consent are
      still at a transitional stage in Japan. The doctrine that patients have the right
      to be informed of their cancers and to choose their treatment has not always been
      the best policy in practice. Nevertheless, it seems desirable that approaches to
      disclosure adequately reflect the special needs of each patient and provide as
      much information as possible to allow each patient to make an accurately informed
      decision about treatment options. Such approaches would foster better
      relationships between physicians and their patients and relieve physicians from
      pressure to tell a medical lie.

PMID- 9916480
TI  - [Diagnosis of pulmonary tuberculosis by the amplicor test for Mycobacterium
      tuberculosis in induced sputum].
AB  - The polymerase chain reaction (PCR) technique was compared with the conventional
      smear and culture method for the detection and identification of Mycobacterium
      tuberculosis in 25 induced sputa samples. Sputum induction was performed with an
      ultrasonic nebulizer using 3% hypertonic saline in 27 previously untreated
      patients suspected of active pulmonary tuberculosis clue to chest X-ray findings,
      but who were unable to spontaneously expectorate sputum. All patients received
      anti-tuberculosis drugs for at least 6 months after sputum induction. Two
      patients could not expectorate sputum after hypertonic saline inhalation.
      Microscopy failed to detect positive acid-fast bacilli in 25 induced sputa
      samples. Induced sputa were both PCR- and culture-positive for 10 patients, PCR
      positive and culture-negative for 4 patients, and PCR-negative and culture
      positive for 2 patients. These results suggest that the PCR method is useful in
      diagnosing tuberculosis in induced sputum, and that the results of PCR and
      culture Procedures can complement each other.

PMID- 9916482
TI  - [Interstitial pneumonia preceding systemic sclerosis].
AB  - We describe a 57-year-old man with interstitial pneumonia associated with
      systemic sclerosis. About 3 years prior to the appearance of distinctive signs of
      systemic sclerosis, he was admitted to our hospital with a chronic dry cough. A
      chest roentgenogram on admission revealed reticulonodular shadows in both lung
      fields. There were no abnormal laboratory findings. Open lung biopsy specimens
      revealed patterns indicative of usual interstitial pneumonia, and myxomatous
      connective tissue within the lumen of the airways. Skin biopsy specimens showed
      heightened levels of collagen in the dermis, a finding consistent with systemic
      sclerosis. The patient was given a diagnosis of lung involvement preceding
      systemic sclerosis despite the absence of concurrent skin symptoms.

PMID- 9916483
TI  - [Acetaminophen-induced pneumonitis].
AB  - We report a case of drug-induced pneumonitis caused by acetaminophen taken for
      headache. The patient was a 49-year-old woman who had been taking a common cold
      drug (Benza BlockSP) containing acetaminophen and an anti-gastritis drug for
      headache. Seven days after she began taking acetaminophen, fever, dry cough, and
      dyspnea developed. The patient was admitted to our hospital on December 6,1996.
      Chest X-ray films and computed tomography scans revealed ground-glass and
      reticulonodular opacities. All chemotherapy was discontinued under a presumptive
      diagnosis of drug-induced pneumonitis. Transbronchial lung biopsy specimens
      revealed infiltration of lymphocytes and eosinophils into the alveolar walls and
      interstitum, with granulomotous lesions and macrophages in the alveolar spaces.
      The patient's chest X-ray findings improved and her symptoms subsided after the
      medications were stopped. However, she was given oral prednisolone (30 mg/day)
      because shadows were still evident on chest X-ray films. Prednisolone was
      effective in removing those shadows. A lymphocyte stimulation test was positive
      for acetaminophen. Based on the above findings, acetaminophen-induced pneumonitis
      was diagnosed. To our knowledge, acetaminophen-induced pneumonitis is rare.
      However, when drug-induced pneumonitis is suspended, common cold drugs containing
      acetaminophen should be kept in mind.

PMID- 9916484
TI  - [Allergic granulomatous angiitis associated with cerebral infarction, myo
      pericarditis and acute respiratory failure due to eosinophilic pneumonia].
AB  - We encountered a 23-year-old woman with allergic granulomatous angiitis (AGA)
      associated with cerebral infarction, myo-pericarditis, and acute respiratory
      failure due to extended eosinophilic pneumonia. She underwent emergency treatment
      at our hospital because of right hemiparesis and impaired consciousness. AGA was
      suspected because the patient had a history of bronchial asthma accompanied by
      pulmonary infiltrations with eosinophilia, and presented with diffuse pulmonary
      infiltrates, pericardial effusion, diffuse hypokinesis of myocardium, cerebral
      infarction and marked peripheral eosinophlia. Pulmonary eosinophilia was
      confirmed by examination of broncho-alveolar lavage fluid. Myocardial tissue
      biopsy specimens revealed fibrous granulation indicative of myocarditis. The
      patient responded well to corticosteroid therapy.

PMID- 9916485
TI  - [Recurrent pneumomediastinum in the course of interstitial pneumonia associated
      with dermatomyositis].
AB  - A 59-year-old woman with dermatomyositis suffered pneumomediastinum twice during
      steroid therapy for aggravated myositis. In both instances, pneumomediastinum
      occurred when the patient's aggravated myositis was in remission. Plain chest X
      ray films showed a slit-like air lucency around the left pulmonary artery. This
      indicated that air entered the mediastinum through the left hilum. Although
      pneumomediastinum associated with dermatomyositis is considered to be fatal, in
      our patient each instance of pneumomediastinum spontaneously disappeared very
      quickly. The favorable course of our patient seemed to be associated with her
      high elevated levels of serum creatine kinase and seropositive results for anti
      Jo-1 antibody.

PMID- 9916486
TI  - [Lung abscess resulting from esophageal carcinoma successfully treated with
      intraesophageal covered self-expandable metallic stent].
AB  - An 82-year-old man was admitted to our hospital with high fever and back pain. He
      already suffered from esophageal carcinoma and expandable metallic stent had been
      inserted because of esophageal stenosis. A chest x-ray film obtained on admission
      showed infiltrative shadows in the right lower lung filled. The diagnosis of lung
      abscess was made on the basis of aspirate findings. Despite closed drainage,
      antibiotic treatment, and fasting therapy, progressive pulmonary infiltrates
      developed. Esophagography and esophagoscopy revealed that an esophageal fistula
      due to an advanced esophageal carcinoma had caused the lung abscess. An
      additional covered self-expandable metallic stent (EMS) was placed on the surface
      of the esophageal carcinoma, close to the esophageal fistula. This promptly
      resolved the lung abscess. Our conclusion was that the covered-EMS can be
      effective for the palliation of esophagorespiratory fistulas.

PMID- 9916487
TI  - [Rheumatoid nodule diagnosed by thoracoscopy using flexible fiberoptic
      bronchoscope].
AB  - A 51-year-old man had been treated at a nearby hospital since 1993 for rheumatoid
      arthritis. Right pectoralgia developed in December 1994, and the patient
      consulted a nearby hospital, which detected right pleural effusion retention was
      pointed out on chest x-ray films. The patient was referred and admitted to our
      hospital. Rheumatic pleurisy was suspected because of a high serum rheumatoid
      factor(RF)level and high RF and high rheumatoid arthritis hemagglutination levels
      in the pleural effusion. However, due to a high adenosine deaminase level in the
      pleural effusion tuberculous pleurisy could not be ruled out. After drainage
      through a trocar catheter, the thoracic cavity was examined by thoracoscopy
      through the site of catheter insertion. As a result, sporadic bluish white
      nodular lesions were observed on the pleura. Granuloma formations presenting a
      palisade arrangement of giant cells were also observed, and pathologically
      diagnosed as rheumatoid nodules, thus providing the basis for a diagnosis of
      rheumatic pleurisy. Treatment with an increased dose of prednisolone achieved a
      rapid remission of the pleural effusion. Our experience underscored the
      usefulness of thoracoscopy as a means diagnosing of rheumatic pleurisy.

PMID- 9916488
TI  - [The French health care system and its reform].
AB  - The French health care system is characterized by its social insurance scheme
      with universal coverage, freedom of prescription and of location by the doctor,
      fee-for-service payment by patients, and free choice of doctor by patients, which
      essentially tends to inflate its health expenditures. Thus, the health
      expenditures of France has been increasing over the average expenditures of other
      European countries. Under the principle of autonomy of the social insurance fund,
      the increase in medical expenditures has been absorbed by a decrease in the
      reimbursement rate and an increase in the contribution rate of the insured.
      However, it is no longer possible to cope with this financial crisis by these
      traditional measures because of the worsening of the unemployment problem.
      Nowadays, the increase in the contribution rate is regarded as one of the
      important reasons for the economic stagnation of the French society. In order to
      cope with this difficult situation, the French government has changed its health
      policy from the demand side strategy to the supply side strategy. The concrete
      plan of this policy was presented by Prime Minister Alain Juppe (the Juppe plan).
      The plan consists of; 1) unification of the medical insurance scheme, 2)
      establishment of a ceiling on medical expenditures, 3) regionalization of health
      policy, 4) disclosure of medical information, 5) introduction of medical
      references, 6) creation of a social protection scheme for the dependent elderly,
      7) introduction of an object tax for the social security fund, etc. These
      subjects have been materializing step by step after many twists and turn. The
      most important principles of the plan are the transparency of the medical
      information and the responsibility of each actor within the health system. The
      French government has conducted a lot of international comparable studies of
      health systems. According to the results of a series of active and profound
      discussions, the French government has conducted various social experiments. It
      is very meaningful for the Japanese government to analyze this process of health
      reform occurring in France in order to discuss the health system reforms in
      Japan.

PMID- 9916489
TI  - [Present and future cancer risk assessment of carcinogenic heterocyclic amines in
      humans].
AB  - Heterocyclic amines are formed during high temperature cooking of foods such as
      meat and fish. Although heterocyclic amines are known mutagens and some of them
      are shown to be carcinogenic to experimental animals, the carcinogenic potential
      of heterocyclic amines in humans has yet to be established. The most important
      criteria in determining the relationship between heterocyclic amines and human
      cancers are the strength and consistency of the association, the presence of a
      dose-response relationship, and the biological plausibility of heterocyclic
      amines being human carcinogens. To date, there are too few data to evaluate the
      strength, consistency, and dose response of this relationship in humans. To
      investigate cancer risk posed by heterocyclic amines to humans, an accurate
      estimation of exposure is needed. Validated methods for exposure assessment of
      heterocyclic amines are not available. At present, without any available long
      term biomarkers of heterocyclic amines, it is crucial to improve exposure
      assessment. Most studies concerning the cancer risk assessment of heterocyclic
      amines are based on the exposure levels calculated only by information on the
      consumption of cooked foods and the mean levels of heterocyclic amines in cooked
      foods. Inaccurate exposure assessment can lead to incorrect cancer risk. This
      review describes the present and future problems of the exposure assessment and
      cancer risk assessment of heterocyclic amines.

PMID- 9916490
TI  - [Geographication of centenarians and its related factors in Japan].
AB  - This study explores the factors associated with longevity in Japan by considering
      the geographic distribution of centenarians based on the 1990 population census.
      The proportion of centenarians was calculated based on the population of those
      aged 65 years or older. The findings were 11.0 males and 28.2 females per 100,000
      people aged 65 years or older. In this analysis, the rate ratio, RR, was used as
      an index for fluctuation of centenarians by prefecture. RR is also the proportion
      of centenarians in a prefecture to that in the nation. When the RR of both sexes
      is over 100, the region is defined as high proportion and less than this as low
      proportion. The high proportion regions were located in the western part of Japan
      i.e. from the Chugoku to the Kyusyu district, the low proportion regions were
      located in the eastern part of Japan i.e. from the Tohoku to the Kanto district
      both sexes. The relationship between the geographical distribution of
      centenarians and environmental factors was analyzed. The correlation coefficient
      of the proportion of centenarians and the temperature as index of a regional
      difference was the highest among the factors investigated. After adjusting for
      mean temperature, the mean value of factors associated with a high quality of
      welfare work and of medical service, and that of having leisure time were
      significantly higher in high proportion regions than in low proportion regions.

PMID- 9916491
TI  - [The effects of interferon-alpha on oxygen radical production by human
      neutrophils].
AB  - This study was done to determine if the production and metabolism of reactive
      oxygen species from human neutrophils were modulated by the treatment of
      interferon-alpha (IFN-alpha). Luminol-dependent Chemiluminescence (LmCL)
      responses were inhibited by a high concentration of IFN-alpha (more than 1 x
      10(4) IU/ml) when opsonized zymosan (OZ) and phorbol 12-myristate 13-acetate
      (PMA) were used as stimulants. However, these responses were increased by 1 x
      10(3) IU/ml of IFN-alpha with Ca(2+)-ionophore A23187 stimulation. Lucigenin
      dependent Chemiluminescence (LgCL) responses were inhibited by all
      concentrations. These findings suggest the possibility that IFN-alpha inhibits
      activation of protein kinase C (PKC), whereas the resulting effect might be due
      to the inhibition of myeloperoxidese (MPO) degranulation. Preincubation of human
      neutrophils with IFN-alpha for 30, 60 or 120 minutes and subsequent stimulation
      with OZ, PMA and Ca(2+)-ionophore A23187 caused an increase LgCL responses, while
      inhibiting LmCL responses. These findings suggest that preincubation of human
      neutrophils with a high concentration of IFN-alpha might enhance the NADPH
      oxidase activity, although a relative increase of LgCL was due to the inhibition
      MPO degranulation.

PMID- 9916492
TI  - [A follow-up study on renal tubular dysfunction in women living in the cadmium
      polluted Jinzu River basin in Toyama, Japan. Part 1. Changes in the level of
      exposure to cadmium after soil replacement of polluted paddy fields and the
      related effects on the prognosis of renal tubular dysfunction].
AB  - A follow-up study on renal tubular dysfunction was carried out on 193 female
      inhabitants of the cadmium (Cd)-polluted Jinzu River basin and 40 reference
      subjects living in an adjacent area in 1994-95. They were 54 to 70 years old when
      the initial examination was conducted in 1983-84. In the Cd-polluted Jinzu River
      basin, extensive reclamation of polluted rice fields has been conducted since
      1979; as a result, the average Cd concentrations in polished rice consumed by the
      subjects in the 1994-95 study (0.12 ppm in 1994, 0.14 ppm in 1995) were
      significantly lower than those in the 1983-84 study (0.26 ppm in 1983, 0.29 ppm
      in 1984). The average Cd levels in urine in the follow-up study (7.5 micrograms/g
      Cr. in 1994, 7.7 micrograms/g Cr. in 1995) were also significantly lower than
      those in the initial study (13.5 micrograms/g Cr. in 1983, 13.3 micrograms/g Cr.
      in 1984). However, the mean values for urinary excretion of beta 2-microglobulin
      (beta 2-m) (3.9 mg/g Cr. in 1994, 3.7 mg/g Cr. in 1995) and glucose (203 mg/g Cr.
      in 1994, 251 mg/g Cr. in 1995) in the follow-up study were significantly higher
      than those obtained at the initial examination (2.0 mg/g Cr. and 125 mg/g Cr. in
      1983 and 1.1 mg/g Cr. and 78 mg/g Cr. in 1984 for beta 2-m and glucose excretion,
      respectively). The magnitude of increase in urinary excretion of beta 2-m and
      glucose in inhabitants of the Cd-polluted area was significantly higher than that
      of the inhabitants of the reference area. Moreover, an increase was observed in
      the prevalence of renal tubular dysfunction determined by urinary beta 2-m
      exceeding 10 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine
      only among inhabitants of the Cd-polluted area; it is noteworthy that 31 new
      cases of renal tubular dysfunction were observed in the follow-up study. These
      results indicate that renal tubular dysfunction among inhabitants of the Cd
      polluted Jinzu River basin is irreversible and progressive, and many new cases of
      renal tubular dysfunction were also noted over a period of 11 years, despite the
      fact that Cd exposure had decreased over the past 11 years.

PMID- 9916493
TI  - [Infants born with development disorders. What about the long-term statural
      development? What are the therapeutic possibilities?].
AB  - Intrauterine growth retardation (IUGR), defined as birth weight and/or length
      less than 3rd percentile (P) or less than-2 standard deviations (SD), concerns
      about 3% of newborns. About 85% born IUGR show spontaneous postnatal catch-up to
      a height > P3 or > -2 SD during the first two years of life. After the age of 4
      year, the children without catch-up will remain short up to final height.
      Classical growth hormone (GH) deficiency usually does not seem responsible for
      the absence of catch-up in those children. A two-year GH therapy at
      supraphysiological doses increases growth velocity. The effect of this treatment
      on final height remains to be studied, as well as optimal treatment's modalities.
      Attention should be paid on the possible side-effects. Finally, the evaluation of
      the psychological impact of GH treatment will be critical.

PMID- 9916494
TI  - [Nuclear accidents and iodine prophylaxis. Part 1: Risks due to irradiation of
      the thyroid gland].
AB  - In the frame of the emergency procedures in the case of an accident in a nuclear
      plant, this paper presents a survey of the information available on the risks
      related to the irradiation of the thyroid gland. Attention is focused on thyroid
      cancer resulting from an exposure to radioactive isotopes of iodine and
      especially and iodine-131. The consequences of the medical exposures as well as
      of the Hiroshima and Nagasaki irradiations are recalled first. Then the recently
      available informations on the effects on the populations exposed after the
      Tchernobyl accident are analysed more in details. Ten years after the accident,
      the most striking and the least questionable effects is a significant increase of
      the incidence of differentiated thyroid cancer in children, in the areas most
      exposed to the initial radioactive clouds. Young children are particularly
      vulnerable to this type of cancer which is of aggressive nature and shows a short
      latency period. These observations justify an iodine prophylaxis for the
      populations living in the vicinity of nuclear plants. Special attention should be
      paid to the protection of young children.

PMID- 9916495
TI  - [Capitation contract financing of primary health care: a possible alternative to
      traditional payment for service--part 1].
AB  - Worldwide health systems are faced with additive and complex problems: a cost
      containment willingness, growing expenses for the health care budgets
      particularly in relation with the new technologies, questioning about true
      quality of provided care from results indicators. Health care financing is one of
      the major determinants of the nature and the comprehensive quality of the system:
      its aim to promote suitable processes and behaviors, to dissuade inadequate ones,
      in a context of efficiency (efficacy with minimal cost), as for politic decidors,
      as for the patients, as for the providers, as for the insurers/funders. A
      comparative and critical approach of the international scientific literature
      shows that partial fixed capitation payment is an interesting alternative for the
      total fee for service. Taking into account many experiences, a proposal for a
      cumulated financing for the practices is made: a structural part, a fixed
      capitation payment (the most important), a fee for service one, a target payment
      one, and a patient personal participation.

PMID- 9916496
TI  - [Zolmitriptan].
AB  - One of the outstanding therapeutic revolutions of this last decade has been the
      introduction of selective serotonin agonists in the acute treatment of migraine.
      After sumatriptan, introduced in Belgium in 1992, other "triptans" are emerging.
      The efficacy and the pharmacoeconomic profile of zolmitriptan, the second
      "triptan" now available in Belgium, are reviewed and the arrival of a third
      triptan, naratriptan is announced.

PMID- 9916497
TI  - [Multifocal breast neoplasm with bone involvement].

PMID- 9916498
TI  - [Treatment strategies of alcoholism].

PMID- 9916499
TI  - [Symposium: frightening chest pains. Frightening chest pains of esophageal
      origin].

PMID- 9916500
TI  - [Chest pains related to pain of spinal origin].

PMID- 9916501
TI  - [The Order of Physicians].

PMID- 9916502
TI  - [Association between antiphospholipid antibodies and arterial or venous
      thrombosis/thrombocytopenia].
AB  - The relationship between thrombotic or thrombocytopenic complications and the
      existence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) was
      studied in 146 patients with systemic lupus erythematosus (SLE). The prevalence
      of arterial thrombosis was obviously higher in patients who had both aCL and LA
      than in patients with either aCL or LA alone or in those with neither. Since a
      substantial fraction of the former group of patients with arterial thrombosis
      also had thrombocytopenia, there is a possibility that aCL and LA might enhance
      platelet activation and aggregation. To test this hypothesis, we studied the in
      vitro effects of aCL and LA on the enhancement of platelet activation by flow
      cytometric analysis using anti-CD62P and anti-CD41 monoclonal antibodies directed
      against platelet activation-dependent granule-external membrane (PADGEM) protein
      and platelet glycoprotein IIb (GPIIb). The IgG fraction purified from aCL+.LA+
      plasma apparently enhanced platelet activation induced by adenosine diphosphate
      (ADP) at a low concentration, but IgG fractions from aCL+.LA- or aCL-.LA+ plasma
      did not cause enhancement of platelet activation. These results suggest that aCL
      and LA may cooperate to promote platelet activation, and may be involved, at
      least partially, in the pathogenesis of arterial thrombosis in patients with SLE.

PMID- 9916503
TI  - [Sampling and quality assurance].
AB  - For the efficient operation of clinical laboratories, automated biochemical
      analyzers have been improved. Large rapidly analyzing and multichannel analyzers,
      and small or mid-sized multiple component analyzers are now commercially
      available and widely use. Such apparatus might require only a small amount of
      specimen and reagent to assay one analyte. Performance has been increased
      annually. In this report, we discuss whether this performance, sampling of
      specimen, sampling of reagent, and mixing effect of reaction mixture or diluted
      specimen affect the accuracy and precision of measurements.

PMID- 9916504
TI  - [Endothelial nitric oxide synthase gene polymorphism and hypertension].
AB  - Nitric oxide (NO) is produced by endothelial cells and serves as a potent
      vasodilator. Several lines of evidence have shown that NO plays an important role
      in the regulation of blood pressure and regional blood flow. Endothelial NO
      synthase (eNOS) gene polymorphisms exhibit a positive association in myocardial
      infarction and smoking-dependent risk of coronary artery disease. However, the
      relationship between eNOS gene polymorphisms and hypertension is controversial.
      To examine the possible involvement of the eNOS gene in the genetic basis for
      hypertension, we identified genotypes for 2 eNOS gene polymorphisms in 166
      hypertensive and 174 normotensive populations in Aomori prefecture, in northern
      Japan. The specific genotypes for Glu298Asp missense variant and variable numbers
      of tandem repeats in intron 4 (eNOS 4b/4a) were isolated using allele specific
      gene amplification and restriction fragment length polymorphism. The 298Asp
      variant was significantly correlated to hypertension in these groups (odds ratio,
      1.8; 95% confidence interval, 1.1-3.2). The allelic frequencies of 298Asp for
      Glu298 in hypertensive patients were significantly higher than those in
      normotensive subjects (0.136 vs 0.083, p < 0.05). However, disequilibrium of
      eNOS4b/4a was absent between these 2 groups. These results suggest that Glu298Asp
      is a genetic susceptibility factor for hypertension.

PMID- 9916505
TI  - [Autoantibodies to heparin polysaccharides bind to vascular endothelial cells].
AB  - Heparan sulfate, a glycosaminoglycan component of vascular endothelial
      proteoglycans, provides the anticoagulant functions associated with heparin on
      the endothelial cell surface. We have demonstrated the presence of spontaneous
      occurring antibodies to heparin polysaccharides (HPS) in humans. Elevation of
      serum anti-HPS antibodies were closely associated with the prevalence of
      thrombosis or fetal loss in patients with autoimmune disease. Affinity purified
      anti-HPS antibodies inhibited heparin dependent formation of thrombin
      antithrombin III complexes. In order to further analyze these autoantibodies, a
      murine IgG monoclonal anti-HPS antibody, designated H16, was generated. H16 mAb
      specifically bound to heparin, heparan sulfate and human umbilical vascular
      endothelial cells (HUVEC). The binding of H16 mAb to HUVEC was specifically
      inhibited by heparin. Further, H16 mAb inhibited the binding of antithrombin III
      to heparin in a dose dependent manner. These results indicate that this mAb could
      recognize antithrombin III-binding sites on vascular endothelial heparan sulfate,
      leading to procoagulant states through the inhibition of heparin/heparan sulfate
      dependent anticoagulant process.

PMID- 9916506
TI  - [Molecular patho-biochemistry and genetic diagnosis for plasminogen
      apolipoprotein (a) gene family related to atherosclerosis and thrombosis].
AB  - Plasminogen is a key proenzyme of plasmin in the fibrinolytic and thrombolytic
      systems, the deficiency of which leads to a mild thrombotic tendency. Plasminogen
      binds to fibrin as well as to the surface of endothelial cells and
      monocytes/macrophages, where it is activated to plasmin. Individuals with
      dysplasminogenemia were analyzed by a combination of PCR and restriction
      digestion. Among 125 unrelated families, an Ala601-Thr mutation accounted for
      about 94% of cases, while a Val355-Phe mutation was found in four unrelated
      families. A new mutation, Asp676-Asn, has been identified in two cases. To
      facilitate the rapid genetic diagnosis of dysplasminogenemia, we also developed a
      method that combines an amplification refractory mutation system and rapid
      automated capillary electrophoresis. Apolipoprotein(a) [apo(a)] is a protein
      component of lipoprotein(a), high plasma levels of which constitute a risk factor
      for atherosclerotic thromboembolic disease. Since apo(a) is very similar to
      plasminogen in terms of amino acid sequence, it inhibits plasmin generation by
      competing with plasminogen's binding to fibrin and endothelial cells. Although
      the plasma Lp(a) concentration roughly correlates with the size and number of
      Kringle 4 repeats of apo(a), a significant variation in the Lp(a) level exists
      among individuals having the same inform. We subclassified the apo(a) gene into
      four types (A-D) by polymorphisms in its 5'-flanking region. We also measured
      plasma Lp(a) concentrations in vivo and examined expression of the gene by in
      vitro assay. Homozygotes of type C had higher Lp(a) levels than those of type D,
      and the relative expression of type C was higher than that of type D in vitro.
      Thus, Lp(a) concentrations in human plasma are predetermined at the genetic level
      by extensive polymorphisms in both the 5'-alleles and the numbers of Kringle 4
      repeats.

PMID- 9916507
TI  - [Lipoproteins in clinical laboratory medicine].
AB  - The characteristics and metabolism of lipoproteins were reviewed. Apolipoproteins
      has been studied in the fields of neurological diseases as well as
      hyperlipidemia. A highly significant association between apolipoprotein E (ApoE)
      epsilone 4 allele and late-onset familial and sporadic Alzheimer's disease (AD)
      was reported. The recent studies also described the following: (1) late-onset
      familial AD linked to the proximal long arm of chromosome 19; (2) the presence in
      the CSF of several proteins, one of which was ApoE, what bound to immobilized
      amyloid beta-peptide (beta A4) with high avidity; and (3) staining by antisera to
      ApoE of senile plaques, neurofibrillary tangles, and cerebral vessel amyloid
      deposits in AD brains. Furthermore, (4) both purified ApoE isomers, ApoE3 and
      ApoE4, bound to beta A4 synthetic peptide, forming a complex that resisted
      dissociation by boiling in sodium dodecyl sulfate, but the isomers showed
      different kinetics in doing so: binding by ApoE4 was observed in minutes, while
      binding by ApoE3 required hours; and (5) ApoE4 did not bind to beta A4 peptide at
      pH less than 6.6, while ApoE3 bound to beta A4 peptide from pH7.6 to 4.6. We
      studied ApoE phenotype expression and the corresponding allele frequencies
      (epsilon 2, epsilon 3 and epsilon 4) in Japanese patients with late-onset
      sporadic AD. The frequency of the ApoE epsilon 4 allele was obviously high in AD
      patients compared with the controls, but it was not different between vascular
      dementia patients and the controls. These results suggest that ApoE isoforms may
      play a functional role in the pathophysiology of late-onset familial and sporadic
      AD and that the isoform-specific difference in beta A4 binding may be involved in
      forming the AD lesion.

PMID- 9916508
TI  - [Progress in laboratory medicine in chronic myeloid leukemia].
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder that is
      characterized by splenomegaly and marked elevation of the blood leukocyte count
      with granulocyte in maturity. Ph chromosome was identified in CML in 1960 and was
      found to clearly result from reciprocal translocation between chromosome 9 and
      chromosome 22 (t(q;22)) (q34;q11). CML arises from a single pluripotent
      hematopoietic stem cell with the Ph chromosome and demonstration of the Ph
      chromosome in blood or marrow cells establishes and unequivocal diagnosis of CML.
      The Ph chromosome is recognized as the cytogenetic result of a rearrangement of
      the ABL gene on chromosome 9 and the BCL gene on chromosome 22, which leads to
      the creation of a BCR/ABL fusion gene on chromosome 22. Abnormal ABL-related
      protein with increased tyrosine kinase activity suggested a molecular mechanism
      of CML. The BCR/ABL fusion gene can be found not only in the chromosome but in
      interphase nuclei by fluorescence in situ hybridization (FISH). We employed both
      fluorescence activated cell sorter (FACS) and FISH to study the lineage
      involvement of individual stem cells and progenitor cells in patients with CML.
      Evidence of BCR/ABL fusion was found in pluripotent stem cells (CD34+, Thy1+),
      myeloid cells, B progenitor cells (CD34+, CD19+) and T/NK progenitor cells
      (CD34+, CD7+, CD5+) but not mature T cells (CD3+) or natural killer cells (CD3-,
      CD56+). These data suggested that BCR/ABL gene fusion occurs in pluripotent stem
      cells and that Ph+ T cells and natural killer cells are eliminated during
      differentiation.

PMID- 9916510
TI  - [Relationship between apoptosis-related markers and cardiomyopathy].
AB  - Increasing interest has been focused on the role of apoptosis in pathogenesis of
      idiopathic cardiomyopathy. Interactions between soluble Fas, tumor necrosis
      factor-alpha (TNF-alpha) and Fas ligand have been reported to play a pivotal part
      in signal transduction of apoptosis. Thus, we measured serum levels of apoptosis
      related markers, namely sFas, TNF-alpha and two types of its receptor TNF-RI and
      TNF-RII in the patients with idiopathic cardiomyopathy. Serum level of TNF-alpha
      was higher in dilated cardiomyopathy (DCM) group as well as in hypertrophic
      cardiomyopathy (HCM) group than in the control group. There were significant
      correlation among TNF-alpha, TNF-RI and TNF-RII in DCM group. However, only
      slight tendencies among these parameters in HCM group, indicating different
      pathogenesis from DCM. No transcardiac production of TNF-alpha, TNF-RI and TNF
      RII was found in cardiomyopathies in the present study. These data suggested that
      apoptosis-related markers could be used for the detailed classification of
      cardiomyopathy. Furthermore, the simultaneous measurement of receptors and their
      ligands of apoptosis-related markers might underscore clinical implications.

PMID- 9916511
TI  - [Urinary excretion of dehydroepiandrosterone and its metabolites in normal young
      adult women].
AB  - Urinary DHEA and its metabolites in healthy young female were measured by
      capillary gas chromatography. The subjects achieved normal pubertal development,
      and their adrenal DHEA secretions had reached to the stable state. The diurnal
      variation, fluctuation during the menstrual cycle and seasonal variation of
      urinary DHEA excretion in each subject were relatively low compared with between
      subject variability. We analyzed the urine of the follicular phase in the morning
      because of the high correlation to the daily urinary pattern. The distribution of
      the urinary DHEA excretion in follicular phase of the subjects was in the broad
      range, 80% distributed in the low levels and 20% in the high level. The scattered
      diagram of the ratio of DHEA to deoxy17KS was separated to 2 groups. Each of them
      had a high correlation coefficient. The one group had high DHEA ratio to
      deoxy17KS, and the other group had a low ratio. These findings suggest that the
      urinary DHEA excretion pattern is highly specific in each subject and may be used
      as a measure to see the distinction from the others.

PMID- 9916512
TI  - [Flow cytometric analysis of helper T cell subsets (Th1 and Th2) in healthy
      adults].
AB  - To estimate frequency of T helper (Th) 1, Th2, and other related subsets in T
      cells among healthy Japanese, we determined the frequencies of interferon (IFN)
      gamma- and/or interleukin (IL)-4-producing cells in stimulated peripheral blood
      lymphocytes (PBL) from 51 healthy adults of various ages by three-color flow
      cytometry using FITC-labeled anti-IFN-gamma, PE-conjugated anti-IL-4, and
      peridinin chlorophyll protein (PerCP)-labeled anti-CD4 or anti-CD3 antibody. As a
      result, proportions (mean +/- SD) of IFN-gamma-single positive (conveniently
      called Th1), IL-4-single positive (Th2), and double-positive cells (Th0) in CD4+
      PBL, and homologous cell populations in CD3+ PBL (Th1 type, Th2 type, and Th0
      type cells) were 21.3 +/- 8.2%, 2.7 +/- 1.1%, 1.9 +/- 1.0%, 39.5 +/- 13.5%, 1.7
      +/- 0.8%, and 1.8 +/- 1.0%, respectively. Percentages of Th1 and Th2 were roughly
      consistent with those reported previously. Proportions of Th1, Th2, Th1 type, and
      Th2 type cells were found to increase with the age, whereas there were no
      significant difference in sex at least in 20s. Furthermore, positive correlation
      was seen between Th1 and Th1 type (r = 0.79), Th2 and Th2 type (r = 0.87), and
      Th0 and Th0 type (r = 0.86). Frequencies of these subsets in each donor were
      maintained at substantially the same levels for at least 3 months, suggesting
      existence of particular and stable Th1/Th2 balance among healthy individuals. As
      reported, 6 patients with atopic dermatitis examined in this study showed
      significantly lower frequencies of Th1 (11.0 +/- 2.5%) as compared with healthy
      donors (p < 0.01), implying usefulness of the immune test.

PMID- 9916513
TI  - [Sensitive enzyme-linked immunosorbent assay for human serum amyloid A (SAA) and
      application to clearance study].
AB  - Serum amyloid A (SAA), an apolipoprotein of high density lipoprotein (HDL), is a
      sensitive acute phase reactant. We established a sandwich type enzyme-linked
      immunosorbent assay for human SAA utilizing a monoclonal antibody and polyclonal
      antibodies. This assay was sensitive enough to detect SAA at 40 pg/ml. The use of
      nonionic detergent, Tween-20, in reaction buffer was essential to enhance
      specific binding of SAA to antibodies and reduce nonspecific binding to plastic.
      The values by this assay showed a good agreement with those by previously
      established latex agglutination immunoassay. Plasma clearance of human SAA was
      studied in mice by injection with SAA-rich human HDL and serial SAA measurement
      by the present assay. Half-life of injected SAA was 55 minutes, similar to mean
      of the reported value of murine SAA isotypes.

PMID- 9916514
TI  - [Semi-quantitative detection of Helicobacter pylori using immunohistochemical
      staining].
AB  - Several methods have been used for the detection of Helicobacter pylori (HP)
      infection. However, few reports have evaluated the accuracy of each method and
      compared the level of HP infection. HP infection was evaluated semi
      quantitatively using immunohistochemical staining and accuracy of several methods
      to detect HP infection were compared. Biopsy specimens, obtained from a total 64
      patients who underwent endoscopy for evaluation of gastroduodenal diseases, were
      studied using a rapid urease test, culture method, and immunohistochemical
      method. The infection was graded according to the number of the individual
      bacteria seen in a highly magnified visual field, and defined as follows: (0) =
      0; (1+) < 10; (2+) = 10-29; (3+) = 30-99, (4+) > 100. The rapid urease test had a
      sensitivity of 53%, specificity of 100%, and accuracy of 73%. The culture method
      had a sensitivity of 75%, specificity of 100%, and accuracy of 86%. Sensitivity
      of rapid urease test and the culture method decreased in a positive correlation
      to the decrease in total number of HP bacteria counted. Using the rapid urease
      test, sensitivity was < 30% when the grade of HP infection was (2+) or less,
      while 100% sensitivity was obtained only when the grade of HP infection was (4+).
      On the other hand, sensitivity of culture method, remained between 80 and 90%
      when HP infection was (2+) or more. The rapid urease test and culture of HP may
      result in false negative tests for mild infection although those have high
      sensitivity and specificity for moderate to severe infection. Immunohistochemical
      stain provides a reliable semi-quantitative diagnosis of HP infection. Clinicians
      should be aware of the characteristics of each method to detect HP infection, and
      select the appropriate ones for their purpose.

PMID- 9916515
TI  - [Myopathology of the intrinsic laryngeal muscles in neurodegenerative diseases,
      with reference to the mechanism of vocal cord paralysis].
AB  - To investigate the mechanism of the vocal cord abductor paralysis (VCAP) in the
      neurodegenerative diseases, the intrinsic laryngeal muscles (the crycothyroid,
      the interarytenoid, and the posterior crycoarytenoid muscles) from 41 autopsied
      cases were histologically examined: 10 cases of amyotrophic lateral sclerosis
      (ALS), 10 of Parkinson's disease (PD), 9 of multiple system atrophy (MSA), 4 of
      Machado-Joseph disease (MJD), 4 of progressive supranuclear palsy (PSP), 1 of
      familial amyloidotic polyneuropathy (FAP), and 3 of cerebrovascular diseases as a
      control. According to the distribution of the neurogenic changes among above
      described three intrinsic laryngeal muscles, three forms were raised: 1. The
      totally paralytic form showing that all the three muscles developed neurogenic
      atrophy. This form includes ALS, MJD, and FAP. 2. The posterior muscle-paralytic
      form showing that only the posterior crycoarytenoid muscle was selectively
      involved. This form includes MSA. 3. The nonparalytic form showing no
      morphological abnormalities in any of the intrinsic laryngeal muscles. This type
      includes PD and PSP. In this nonparalytic form, supranuclear mechanism such as
      pyramidal or extrapyramidal tract involvement may cause VCAP through the
      increased laryngeal muscles tone. Considering that VCAP can be seen in any of the
      above-described forms, our results indicate that the mechanism of VCAP is
      different among the neurological disorders.

PMID- 9916516
TI  - [Double filtration plasmapheresis (DFPP) in chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP)].
AB  - We studied the therapeutic characteristics of double filtration plasmapheresis
      (DFPP) in 14 patients with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP). The patients were classified into 2 subgroups of
      the responders (7 patients) and the non-responders (7 patients) to DFPP. The
      responders to DFPP were designated as those showing the improvement 2 or more
      grades in measures the activity of daily living by the modified Rankin scale
      (MRS). All these patients underwent neurological assessment, CSF study,
      electrophysiological studies at the beginning and end of treatment. Sural nerve
      biopsy study was performed in 10 cases. Neurological function was assessed
      serially using a quantitative neurological disability score (NDS). At the
      beginning of treatment, there were no significant differences in various
      measurements between the responders and the non-responders except for the
      frequency of demyelination. In responders, significant improvement was found in
      mean changes in MRS, NDS, motor nerve conduction velocity, compound muscle action
      potential, distal motor latency, while in non-responders, all measures remained
      unchanged or worsened. Muscle wasting was seen in 3/7 responders and 4/7 non
      responders, and denervation potentials in needle EMG were seen in 1/7 responders
      and 3/7 non-responders. Four patients of the responders were classified as
      chronic relapsing course, and 6 patients of the non-responders as chronic
      progressive course. We conclude that DFPP was useful for the subgroups of CIDP
      patients, but the underlying immuno-pathological background that determine the
      efficacy of plasmapheresis should be elucidated.

PMID- 9916517
TI  - [Effect of long-term administration of prednisolone on serum creatine kinase and
      muscle pathology of mdx mouse].
AB  - For palliative therapy of Duchenne muscular dystrophy (DMD), corticosteroids have
      been tried since 1970. According to recent reports, corticosteroids maintained
      muscular strength to some extent and prolonged period of ambulation. However,
      their mechanism of action is mostly unclear. In the present study, mdx mice were
      injected with 0.6 mg prednisolone 3 times a week for 30 weeks. Serum creatine
      kinase (CK) values remained 23% of controls. In muscle pathology of the
      quadriceps muscle, fibers with peripheral nuclei were increased, suggesting
      reduction of muscle necrosis. In pathological examination of liver, pyknotic
      cytoplasmic masses and formation of vacuoles were observed. Present study showed
      that prednisolone might attenuate muscle fiber necrosis at least for 30 weeks.
      Prednisolone may reduce secondary tissue reactions, which develop more serious
      muscle damage.

PMID- 9916518
TI  - [Motor association cortex activity in Parkinson's disease--a functional MRI
      study].
AB  - The purpose of this study was to examine the activation of motor association
      cortex using functional magnetic resonance imaging (fMRI) in patients with
      Parkinson's disease (PD) and control subjects during performed hand movements.
      There were 26 patients with PD (12 patients with Hoehn and Yahr stage I-II, 14
      patients with stage III) and 8 control subjects. Functional imaging was performed
      using a 1.5 tesla MRI system equipped with a single-shot, echo-planar pulse
      sequence. The significant signal changes were observed within the primary
      sensorimotor area, the supplementary motor area (SMA), and the parietal
      association area in both PD and control subjects. In PD subjects, the SMA was
      less activated than in control subjects; there were significant differences in
      the number of pixels activated in SMA between control and Yahr III group (p <
      0.01), and between Yahr I-II and Yahr III group (p < 0.01). Our results
      demonstrated that movement related cerebral activity in the SMA is reduced in PD
      subjects, consistent with previously published data using other methods. It is
      well known from anatomical studies that one of the major cortical outputs of the
      basal ganglia is the SMA. This may explain the hypoactivation of the SMA in PD.
      Studies using fMRI provide a promising method not only for localizing cortical
      activation related to voluntary movements but also for investigating
      pathophysiology of movement disorders.

PMID- 9916519
TI  - [Somatic mosaicism of p(CTG)n expansion in a case of myotonic dystrophy with
      parotid tumor].
AB  - Myotonic dystrophy (MD) is an autosomal dominant systemic disorder with an
      unstable expansion of the CTG triplet repeat in the 3'-untranslated region of the
      gene encoding myotonine protein kinase (DMPK) which maps to chromosome 19q13.3.
      Somatic mosaicism of CTG repeats in MD has been reported; and it has been
      observed that CTG repeats in tumor tissues associated with MD are more expanded
      than the other tissues. It is not rare that parotid tumors are found in patients
      with MD. We performed Southern blot analysis for tissues from the parotid tumor,
      the normal parotid gland, the skeletal muscles, and the leukocyte from a 60-year
      old patient with MD. CTG repeat was most expanded in the parotid tumor, and the
      normal parotid gland had longer expansion of CTG repeat than the skeletal
      muscles. The leukocyte had the shortest expansion of CTG repeat. The expansion of
      CTG repeat in the parotid tumor may be related to active cell division and may
      underlie the occurrence of tumors in MD.

PMID- 9916520
TI  - [Disturbance of deep sensation in medial medullary syndrome. Topographical
      localization of medial lemniscus in the medulla oblongata].
AB  - Medial medullary infarction is characterized by ipsilateral hypoglossal nerve
      palsy with contralateral hemiparesis and disturbance of deep and discriminative
      sensory perception. We examined the extent and distribution of disturbances in
      deep sensation and compared the findings with the lesion location in the medial
      lemniscus detected by MRI in 3 patients with medial medullary infarction. We
      classified the lesion location into 2 groups; type I and type II. Type I was
      ventral to the middle medial lesion of the medial lemniscus, and type II was
      ventral to the dorsal medial lesion. In our series, type I (Case 1) impairment of
      the three kinds of deep sensations was more severe in the lower extremities than
      in the up-per extremities. In type II (Cases 2, 3) the severity or impairment in
      the upper extremities was moderate or severe and nearly equal to that in the
      lower extremities. There was no difference in the severity of impairment for the
      four kinds of discriminative sensations. In the literature, type I (8 patients)
      impairment of position sense in deep sensation was found in 1 of 7 patients in
      the upper extremities and 5 of 7 patients in the lower extremities. Impairment of
      vibration sense was found in 1 of 7 patients in the upper extremities and in all
      patients in the lower extremities. In type II (14 patients) severe impairment of
      position and vibration sense in deep sensation was found in 3 patients in the
      upper extremities equal to that in the lower extremities. There was no tendency
      in the severity of impairment of four kinds of discriminative sensations.
      Including our 3 cases and 22 in the literature, impairment of deep sensation was
      more severe in the lower extremities than in the upper extremities in type I (9
      patients) and the extent was none (7), mild or moderate (2) in the upper
      extremities, mild (2), moderate (1), severe (2), obscure (4) in the lower
      extremities, while in type II (16 patients) the severity in the upper extremities
      was nearly equal to that in the lower extremities and the extent was none (1),
      mild or moderate (1), severe (5), obscure (9) in the upper extremities, none (2),
      mild or moderate (1), severe (6), obscure (7) in the lower extremities. It is
      concluded that hemiparesis appeared with lesions located in the pyramidal tract
      of the medulla, hemiparesis and disturbance of deep sensation in the upper and
      lower extremities, predominantly in the lower extremities with the lesion of the
      pyramidal tract to the middle of medial lemniscus in the medulla, hemiparesis and
      disturbance of the upper and lower extremities deep sensation with lesions of the
      pyramidal tract to the whole of the medial lemniscus in the medulla. Evaluating
      deep sensation of the upper and lower extremities is useful for speculation of
      the lesion location in the medial lemniscus in medial medullary infarction.

PMID- 9916522
TI  - [Ipsilateral central-type facial palsy and contralateral hemiparesis associated
      with unilateral medial medullary infarction: a case report].
AB  - Clinical pictures of medial medullary syndrome are variable, depending upon the
      extent of the lesion. Facial palsy has rarely been observed even in medullary
      infarction. However, central-type facial palsy is usually found contralaterally
      to the infarct area at the level of the rostral medulla. In the present report,
      we discuss the pathogenesis of the neurological manifestations in a 57-year-old
      man with hypertension. The patient presented with mild left facial palsy of
      central type, right hemiparesis, paresthesia, with deep sensory disturbance of
      the right extremities. An MRI of the brain showed an infarction localized in the
      medial region of the left upper medulla. Although the exact course of the
      supranuclear facial pathways remains controversial, the ipsilateral central
      facial palsy in this patient is considered to have two possible causes: the
      interruption of aberrant fibers of the corticobulbar tract, which branch off and
      swing back at the level of the upper-middle medulla, or the disruption of
      recurrent ascending fibers from the contralateral pyramidal tract, through
      decussation.

PMID- 9916521
TI  - [A case of Guillain-Barre syndrome associated with bilateral ballism: an overlap
      between Fisher's syndrome and Guillain-Barre syndrome].
AB  - A 29-year-old woman developed diplopia and ataxic gait. Neurological examination
      revealed total ophthalmoplegia, cerebellar ataxia, and areflexia. Muscle weakness
      in four limbs was also noted. We diagnosed the patient as having an overlap
      between Fisher's syndrome and Guillain-Barre syndrome. On day 5, she suddenly had
      flinging involuntary movements affecting the face and four extremities. Surface
      EMG recording revealed 1.5- 2 Hz rhythmic grouping discharges. The involuntary
      movements were considered as ballism. Brain CT and MRI could not detect any
      abnormal findings in subthalamic nucleus, but, electrophysiological findings
      revealed CNS lesions. Therefore, the clinical diagnosis also were Bickerstaff's
      brainstem encephalitis. She had high titer of IgG antibody to GQ 1b (1:64,000).
      Sera taken from patients with Fisher's syndrome, Guillain-Barre syndrome with
      ophthalmoparesis and Bickerstaff's brainstem encephalitis during the acute phases
      of these syndromes frequently have IgG antibody to GQ 1b ganglioside. It is
      concluded that some cases of acute ophthalmoparesis subsequent to infection or
      immunization may be categorized as autoimmune diseases. Hence, such disease which
      show external ophthalmoparesis may be designated the "anti-GQ 1 b IgG antibody
      syndrome". This is the first report on the patient with Guillain-Barre syndrome
      and the related disorders who showed ballism.

PMID- 9916524
TI  - [A case of acquired stuttering resulting from striatocapsular infarction].
AB  - Acquired stuttering resulting from a striatocapsular infarction is reported. A 54
      year-old man was admitted to our hospital because of acute onset of stuttering
      and right facial palsy. The patient spoke very slowly. Speech was characterized
      by repetitions and prolongations. We considered that there was no aphasia,
      because comprehensive faculty was normal and neither paraphasia nor word-finding
      difficulty was recognized. Brain CTs and MRI revealed a striatocapsular
      infarction extending from the putamen to the caudate nucleus in the left
      hemisphere. Previously, there were reports of stuttering derived from
      parkinsonism and lesions in the supplementary motor area and thalamus. Therefore,
      we proposed that the stuttering arose from a collapse of basal ganglia circuits
      that connect the cerebral cortex and basal ganglia, including the extrapyramidal
      tract system.

PMID- 9916523
TI  - [A case of early-onset cortical cerebellar atrophy with rhythmic skeletal
      myoclonus in the left upper limb].
AB  - A 19-year-old man developed progressive unsteady gait and speech disturbance two
      years ago. He recently noticed muscle twitches in the left limb. Neurological
      examination revealed scanning speech, saccadic ocular movement, ataxia of trunk
      and limbs predominant on the left side. Rhythmic myoclonus was present at rest
      around the left shoulder and arm, and amplified by raising the left arm. There
      was no myoclonus in the soft palate. MRI revealed only a cerebellar atrophy. This
      patient was diagnosed as having cortical cerebellar atrophy with rhythmic
      skeletal myoclonus (RSM). Tc-99m ECD SPECT showed a decrease in the blood flow of
      the right thalamus when the myoclonus was enhanced by raising the left upper
      limb, which suggests that the cerebello-thalamo-cortical system as well as
      Guillain-McIlaret triangle is involved in the development of RSM.

PMID- 9916526
TI  - [Ictal 99mTC-HMPAO-SPECT in a case of paroxysmal kinesigenic choreoathetosis].
AB  - A case of paroxysmal kinesigenic choreoathetosis (PKC) was described. The patient
      had attacks of paroxysmal choreoathetotic movements lasting 20-30 seconds. The
      attacks were regularly precipitated by sudden and unintentional movements. There
      were no metabolic abnormalities. EEG showed no epileptiform discharges. The
      attacks were subsided after administration of carbamazepine. We studied this
      patient with single photon emission computed tomography (SPECT) using 99mTc
      HMPAO. Ictal SPECT revealed decrease of cerebral blood flow in the basal ganglia
      on the contralateral side of choreothetotic movements. Although the
      pathophysiology of PKC is still uncertain, it is hypothesized that motor
      activities are influenced by the direct pathway (positive feedback) and the
      indirect pathway (negative feedback) from the basal ganglia to the motor
      cortecis. Dysfunction of negative feedback is considered to be common underlying
      mechanisms of hyperkinetic disorders. Our findings support this hypothesis.
      Dysfunction of basal ganglia is likely relevant to the genesis of
      choreoathetosis.

PMID- 9916527
TI  - [Sinus bradycardia induced by talipexole hydrochloride in a patient with
      Parkinson disease].
AB  - We report sinus bradycardia induced by talipexole hydrochloride in a 65-year-old
      man with Parkinson disease. Approximately four hours after he had taken 0.8 mg of
      talipexole hydrochloride, he acutely developed sleepiness, delusion, akinesia,
      and faintness associated with hypotension and sinus bradycardia. Another similar
      episode occurred when he had taken talipexole hydrochloride 1.2 mg/day in
      combination with a daily dose of 200 mg of levodopa and 20 mg of carbidopa. These
      symptoms persisted for 12 hours and diminished gradually without any specific
      treatments. Talipexole hydrochloride, a stimulator of both the D2 and alpha 2
      receptors probably induced bradycardia and hypotension in the present case.

PMID- 9916525
TI  - ["Painful legs and moving toes" and muscle cramps spreading to the bilateral legs
      in a patient with alcoholic polyneuropathy].
AB  - A 37-year-old man with alcoholic polyneuropathy showed involuntary movement as
      intermittent flexion-extension or abduction-adduction of his toes identical to
      "painful legs and moving toes (PLMT)" and muscle cramps. Regarding the sequential
      spreading of PLMT and cramps from unilateral to contralateral leg muscles and
      phasic discharges observed by a needle EMG in the foot muscles during PLMT, we
      suppose that a spinal or supraspinal mechanism was responsible for the production
      of those movements. This case showed novel aspects of PLMT which was induced by
      sensory stimulation of the left lower leg and subsequently initiated cramps. The
      destruction of the lumbar sympathetic ganglion remarkably ameliorated the
      spontaneous PLMT and cramps, whereas sensory stimulation of the left lower leg
      still induced those movements. Therefore, we think that sensory inputs from
      peripheral nerves played a critical role in the generation of PLMT and cramps,
      and abnormal activities of spinal sympathetic nerves exacerbated those
      involuntary movements. Sensory induced PLMT may be a subgroup of this movement
      disorder.

PMID- 9916528
TI  - [Treatment of nocturnal periodic hypoxemia with safrazine hydrochloride in a
      patient with Duchenne muscular dystrophy under nasal intermittent positive
      pressure ventilation].
AB  - Nocturnal periodic hypoxemia occurring in a 25-year-old Duchenne muscular
      dystrophy patient under NIPPV control was successfully treated with monoamine
      oxydase inhibitor (MAOI), safrazine hydrochloride. Five mg of safrazine
      hydrochloride was administered before sleep, and the periodic hypoxemia
      disappeared within 14 days. The effect lasted almost seven months without notable
      side effect. MAOI may be effective for nocturnal hypoventilation through
      suppression of REM sleep as in the case of tricyclic antidepressants. The effect
      of tricyclic antidepressants appears immediately. However, it usually fades away
      within forty days. Safrazine hydrochloride was effective obviously longer than
      tricyclic antidepressants. Consequently MAOI may be a hopeful candidate of
      medication for a treatment of nocturnal periodic hypoxemia in Duchenne muscular
      dystrophy.

PMID- 9916529
TI  - [A case of clinically diagnosed Creutzfeldt-Jakob disease with serial MRI
      diffusion weighted images].
AB  - We reported MRI findings in a 49-year-old woman with clinically diagnosed
      Creutzfeldt-Jakob disease (CJD). She was admitted to our hospital because of
      confusion, which initially appeared 5 weeks prior and was rapidly worsened. Two
      weeks later, she developed myoclonic jerks in her extremities with periodic
      synchronous discharges on EEG. Six months later, she became mutic. Brain MRI at 3
      weeks after the admission demonstrated high signal intensities in the bilateral
      caudate nuclei and putamina on T2 weighted images (T2WIs). Diffusion weighted
      images (DWIs) showed hyperintensities in the basal ganglia and in the parietal
      and occipital cortices. Five weeks later, the abnormal intensities in the basal
      ganglia were still observed on T2WIs but decreased on DWIs. Five months later,
      the increased signal intensities in the basal ganglia had disappeared both on
      T2WIs and DWIs, but new hyperintensities appeared in the insula and the temporal
      area on DWIs. We concluded that DWIs may be useful for the demonstrations of a
      lesion in the cerebral cortex and the spread of lesions.

PMID- 9916530
TI  - [The Military Medical Academy--the national property of Russia].
AB  - Article by the Chief of the Academy has been based on its history of 200 years.
      One of the oldest establishments of medical education has played a great role in
      the development of the national and world medicine. Among the Academy graduates
      of highest merit was N. I. Pirogov, a famous surgeon, who marked a new age in the
      medical science and education and introduced important innovations in the
      casualty treatment on the battlefield. He was the first to apply ether
      anaesthesia and plaster bandage and to have women taking care of the wounded on
      the theater of operations. Academy graduates S. P. Botkin, G. F. Lang and F. I.
      Komarov had founded their own schools of therapy. E. N. Pavlovskii developed a
      study on the focus nativeness of infection and parasite disease process. Every
      year the Academy scientists implement more than 150 research projects for the
      government, ministries and different agencies, defend up to 75 theses on 30
      specialties, conduct more than 20 national and international conferences,
      symposiums and meetings. For the last 35 years the Academy has been training
      medical doctors, scientists and healthcare specialists for 35 countries in
      Europe, Asia, Africa and Latin America.

PMID- 9916531
TI  - [The development of the academic process at the Military Medical Academy].

PMID- 9916532
TI  - [The problem-oriented research laboratories of the Military Medical Academy].

PMID- 9916534
TI  - [The contribution of the Military Medical Academy to the development of Russian
      traumatology and orthopedics].

PMID- 9916533
TI  - [Psychophysiological support for the professional activities of servicemen].
AB  - Optimal solution of the personnel replenishment problem, the necessity of
      training and education process improvement in the training centers and schools,
      the outcome of social, psychological and medical measures greatly depend on the
      overall physical and mental health state of the servicemen and their professional
      training quality. On the basis of their long standing experience the authors
      discuss the traits of the psychophysiological maintenance of the military
      professional activities of servicemen, in particular--the methodology and theory
      of professional psychological selection, the importance of body functional
      indications for the estimation of the fighting capabilities of military units.
      They examine some prospects for the psychophysiological expertise in the
      promotion procedures of commanding officers and make a suggestion that
      psychophysiological maintenance in the Armed Forces would increase its combat
      capabilities and help to avoid some negative effects in military groups.

PMID- 9916535
TI  - [The main stages in the formation and the prospective trends for the development
      of military field therapy].

PMID- 9916536
TI  - [The video endosurgery of emergency pathology of the abdominal cavity organs].
AB  - In this study its authors sum up their practice of emergency treatment of 569
      patients with acute surgical pathology, needing an urgent laparoscopy
      intervention. They present a programme of laparoscopy methods, including a
      complex of organisation and medical problems and in particular those of the
      material base development together with the solution of some training methodology
      and scientific questions. It is emphasized, that the laparoscopy methods have
      great possibilities in the diagnostics and treatment of acute surgical pathology
      cases and that an urgent surgical aid should be expedient. Due to the rational
      application of endovideosurgery methods, the overall lethality was reduced by 1.5
      times, negative after-effects--by 4%.

PMID- 9916537
TI  - [The development of the theory of infectious diseases at the Military Medical
      Academy].

PMID- 9916538
TI  - [The formation and development of the organization and tactics of the Naval
      Medical Service as an academic and scientific discipline].
AB  - Formation and development of the Navy medical service started back in the 30th of
      the XXth century. In 1938 they created a naval and marine sanitary disciplines'
      Chair which was successively a component of the Navy faculty of the 1st Leningrad
      Institute of Medicine, Naval Academy of Medicine and from 1956--a part of the
      Academy of Military Medicine. For 60 years of its existence, the Chair has
      implemented nearly 350 fundamental research projects, more than 50 directives,
      edited some 60 textbooks and manuals and over 60 theses were defended. Its
      students were 59 courses of doctors for ships and navy units and above 300
      administrators.

PMID- 9916539
TI  - [The first higher pharmacy school in Russia].

PMID- 9916540
TI  - The promise of a multiple roles paradigm for women's health research.

PMID- 9916541
TI  - The impact of work-family systems on women's psychological health: an
      introduction.

PMID- 9916542
TI  - Does child care involvement increase or decrease distress among dual-earner
      couples?
AB  - This study addressed how parents' relative involvement in child care is related
      to marital-role quality and psychological distress. These relationships were
      examined in a random sample of 133 mothers and fathers in dual-earner couples.
      Regression analyses employing hierarchical linear modeling techniques indicated
      that the more fathers participated in child care relative to their wives, the
      lower the father's distress. For mothers, the effect of child care involvement
      was complex: Although there were psychological benefits to spending
      proportionally more time involved in child care (lowered distress), these
      benefits were offset by a decrease in marital-role quality, which in turn
      increased distress. These findings indicate that the relation between child care
      involvement and the psychological health of both women and men in dual-earner
      couples is intertwined and complex.

PMID- 9916543
TI  - Change in job conditions and change in psychological distress within couples: a
      study of crossover effects.
AB  - In a random sample of 242 full-time employed men and women in dual-earner couples
      (N = 484), this study estimated the relations between (a) his experiences on the
      job over time and her distress over time and (b) her experiences on the job over
      time and his distress over time. In addition, we explored whether the crossover
      effects were due primarily to experiences with particular job conditions, and
      whether there were gender differences in the magnitude of these associations. The
      participants were interviewed 3 times over a 2-year period. After taking into
      account the relationship between each partner's own job conditions over time and
      her or his own psychological distress, there were significant associations
      between both the time-varying and the stable components of each partner's job
      conditions on the other partner's distress. The findings are discussed within the
      context of the need to expand the models used to study the job stress-illness
      relation to include longitudinal and within-couple crossover effects.

PMID- 9916544
TI  - The psychological effects of work experiences and disagreements about gender role
      beliefs in dual-earner couples: a longitudinal study.
AB  - Using an economically diverse random sample of 300 full-time employed men and
      women in dual-earner couples from two communities in the Northeast, we estimated
      the relation between the direction and magnitude of disagreement about gender
      role ideology (GRI) within couples and psychological distress. We conceptualized
      GRI within couples as both the couple mean or stable gender-role ideology (the
      "couple ideology") and as each partner's deviation from the other partner's
      score. Moreover, for each partner, we estimated the relation between both the
      stable (i.e., mean) component and the change (i.e., time-varying) component of
      GRI and distress. Finally, for each partner we estimated the moderating effect of
      GRI on the relation between job-role quality and distress. Findings are: (a) the
      more egalitarian the husband's average GRI is relative to his wife's, the less
      distressed he is; (b) if over time a wife's GRI becomes less egalitarian relative
      to her husband's, then her distress will be more affected by changes in her job
      role quality; (c) for husbands, as the couple's average GRI becomes more
      egalitarian over time, the effect of job-role quality on distress is lessened;
      and (d) for a man in a couple with a more egalitarian stable GRI, the effects of
      change in job-role quality on distress are less pronounced than for a man in a
      couple with a less egalitarian stable GRI. Results are discussed in terms of new
      conceptions of GRI revealing the dynamic interaction of within-couples' gender
      role ideologies.

PMID- 9916545
TI  - Negative affectivity: how serious a threat to self-report studies of
      psychological distress?
AB  - Serious questions have been raised about the common practice of relying on self
      report measures to assess the relation between subjective role experiences on the
      one hand and both mental and physical health symptoms on the other. Such self
      report measures may reflect a common underlying dimension of negative affectivity
      (NA), thereby leading to spurious results. In this article, we present findings
      from analyses in which we estimate, using a hierarchical linear model, the
      relation between subjective experiences in job and marital roles and self-reports
      of symptoms of psychological distress after controlling for NA in a sample of 300
      full-time employed men and women in married couples. Results demonstrate (a) that
      NA can account for a great deal of the variation in self-reported psychological
      distress, as much as half in the case of the men in the sample; (b) that
      estimates of the relations between a self-reported predictor of social-role
      quality (e.g., marital-role quality, job-role quality) may be biased by failure
      to include NA as a predictor of self-reported psychological distress; (c) that
      the degree of bias in these estimates is dependent on the nature of the
      predictor, and (d) that the role of NA as a confounder does not appear to be
      dependent on gender.

PMID- 9916546
TI  - Sexual functioning and intimacy in African American and white breast cancer
      survivors: a descriptive study.
AB  - This study examines ethnic differences in sexual socialization and attitudes,
      sexual history and current practices, and the effects of treatment in 147 African
      American and White breast cancer survivors. Sex-related research in younger
      healthy populations has shown that cultural values associated with ethnicity
      influence sexual functioning, but small numbers of African American participants
      in previous research in breast cancer survivors has limited what we know about
      that population. In this study, there were few differences between the 2 ethnic
      groups in a predominantly well-educated, high-income, highly functional sample.
      However, African American women were significantly less likely to be comfortable
      with and to practice oral sex, self-touching, and masturbatory behaviors. White
      women were more likely to report that breast cancer had a negative impact on
      their sex lives. These differences in sexual repertoire and functioning should be
      noted by health care practitioners treating the sexual sequelae of breast cancer
      treatment.

PMID- 9916547
TI  - Women HIV sexual risk takers: related behaviors, interpersonal issues, and
      attitudes.
AB  - HIV and AIDS is a growing health risk for heterosexual women, particularly women
      of color (Centers for Disease Control and Prevention, 1997). Our research
      identified 5 types of HIV sexual risk taking in 3 independent samples of adult
      women from a New England Community: Group A women were noted by low to moderate
      levels of the 4 risk markers (i.e., unprotected vaginal sex, perceived partner
      related risk, number of sexual partners, and unprotected anal sex); Group B women
      reported very high frequency of unprotected vaginal sex; Group C women were
      characterized by unprotected anal sex; Group D women had high perceived partner
      risk; and Group E women reported extremely high levels on all 4 HIV risk markers.
      Sexual risk groups were validated by demonstrating significant differences among
      groups on relevant behaviors, interpersonal experiences, and attitudes. Compared
      to other women, higher risk types reported greater behavioral risk practices
      (substance use, prostitution, diverse sexual experience), interpersonal risk
      experiences (sexual abuse, violence), initiation sexual assertiveness, and
      attitudinal risks (psychosocial distress). They reported less interpersonal
      assurance (surety of own and partner's HIV status), sexual assertiveness (for
      condom use and partner communication), psychosocial strengths (sexual self
      acceptance), and transtheoretical readiness for change (condom use efficacy,
      readiness to consider condoms). Results provide additional support for the
      multifaceted model of HIV risk and the transtheoretical model. Suggestions for
      specifically focused interventions are given, depending on the pattern of sexual
      risk taking.

PMID- 9916548
TI  - Salmonellosis in relation to chlamydiosis and pox and Salmonella infections in
      captive falcons in the United Arab Emirates.
AB  - During the spring of 1995, 1996 and 1997 following tests on six peregrine falcons
      (Falco peregrinus) and two gyr falcons (Falco rusticolus), Salmonella typhimurium
      was isolated from liver, spleen and small intestines. Four of the falcons (two
      peregrines and two gyrs) had also contracted Chlamydia infection, three
      peregrines a pox infection and one peregrine a Herpesvirus infection. It is
      believed that this dual infection was fatal for these birds. The disease was
      marked by anorexia, dehydration and green-coloured droppings. Necropsy of all
      falcons revealed discolouration of the liver and enlargement of liver and spleen.
      Miliary necrosis was detected in all livers. A total of 12 salmonella serovars,
      including S. typhimurium, were cultured from faeces of 48 falcons which showed no
      clinical signs.

PMID- 9916550
TI  - Strain differentiation of Clostridium perfringens by bacteriocin typing, plasmid
      profiling and ribotyping.
AB  - Bacteriocin typing, plasmid profiling and ribotyping were used to type 34 food
      and patient Clostridium perfringens isolates from 10 food poisoning cases,
      respectively, outbreaks. In nine cases/outbreaks bacteriocin patterns showed
      identical main groups. Subgroups differed within all cases/outbreaks. Plasmid
      profiles were identical for all isolates within each of three outbreaks. In eight
      food poisoning cases and outbreaks, all the ribotypes of each food and stool
      isolate were found to be identical. All three typing methods give valuable
      results for the characterization of C. perfringens beyond the species level.
      Bacteriocin typing represents a suitable addition to plasmid typing, particularly
      since the results do not show any correlation between losses of plasmids and
      changes in bacteriocin sensitivity patterns. Ribotyping was found to be a
      suitable tool to determine the genetic relationship of C. perfringens isolates in
      the context of food-borne poisoning.

PMID- 9916549
TI  - Subtyping of Streptococcus dysgalactiae and Streptococcus uberis isolated from
      bovine mammary secretions by DNA fingerprinting.
AB  - Streptococcus dysgalactiae and Streptococcus uberis isolated from mammary
      secretions of cows from Tennessee and New Zealand were subtyped using polymerase
      chain reaction-based DNA fingerprinting. Such DNA fingerprinting using primer
      8.6d (5'-GTAACGCC3') resulted in categorizing 116 S. dysgalactiae isolates into
      25 different subtypes, with 17 subtypes observed in isolates from Tennessee and
      eight in isolates from New Zealand. All S. dysgalactiae DNA fingerprint profiles,
      regardless of origin, contained 700- and 330-base pair fragments. The majority of
      S. dysgalactiae isolates (73%) from Tennessee belonged to two subtypes. The
      remaining 23 isolates belonged to 15 different DNA fingerprint subtypes.
      Streptococcus dysgalactiae isolates from New Zealand (n = 32) were grouped into
      eight different subtypes; 66% belonged to two subtypes. A characteristic feature
      of S. dysgalactiae isolates from New Zealand was the presence of a 270-base pair
      DNA fragment seen infrequently in S. dysgalactiae isolates from Tennessee. When
      primer OPE-4 (5'-GTGACATGCC-3') was used, DNA fingerprinting differentiated S.
      uberis from Tennessee (n = 28) and New Zealand (n = 30) into 20 subtypes; 14
      subtypes were observed in isolates from Tennessee, and six in isolates from New
      Zealand. All S. uberis DNA fingerprint profiles, regardless of origin, contained
      1100-, 640-, and 450-base pair fragments. A characteristic feature of S. uberis
      isolates from New Zealand was the presence of a 300-base pair DNA fragment seen
      infrequently in S. uberis isolates from Tennessee. The most common subtypes of S.
      dysgalactiae and S. uberis from Tennessee herds were isolated in milk from
      lactating cows during monthly herd surveys, in milk from cows with clinical
      mastitis, and in mammary secretions from cows during the periparturient period,
      and thus were not confined to one particular stage of lactation. These data
      suggest that S. dysgalactiae and S. uberis from New Zealand are distinct from
      those isolated from the USA, and that DNA fingerprinting can be used as an
      epidemiological tool to differentiate streptococci and identify important sources
      of these mastitis pathogens on dairy farms.

PMID- 9916551
TI  - Isotype-specific immune responses in murine experimental anisakiasis.
AB  - A murine experimental model of anisakiasis has been developed in BALB/c and
      C57BL/10 mice orally inoculated with an Anisakis simplex living third stage larva
      (L3) in order to investigate isotype-specific immune responses against excretory
      secretory (ES) products and crude extracts (CE) from L3. Specific antibody
      production showed similar patterns against both ES and CE antigens with higher
      levels against the latter. The dynamics of the production showed the earliest
      responses in BALB/c, in which antibodies were principally of the immunoglobulin
      (Ig)M isotype. Responses to the IgG1 subclass were mainly produced in the
      C57BL/10 strain. Levels of IgG2a were practically undetectable. With sera from
      C57BL/10 mice high levels of the IgG2b isotype were detected. A slight IgG3
      response was only detected against the CE antigen in the C57BL/10 strain by the
      end of the experiment and IgA responses were very low. Humoral responses against
      A. simplex antigens are different depending on individual characteristics and
      thymus-independent epitopes might be represented into A. simplex antigens and
      their stimuli could be different regarding the murine strain used.

PMID- 9916552
TI  - Experimental mixed infection with Yersinia enterocolitica and Listeria
      monocytogenes in guinea pigs.
AB  - The pathogenesis and the cell immune response (CIR) of guinea pigs after mixed
      infection with Y. enterocolitica and L. monocytogenes was investigated. The
      guinea pigs were infected per os with 1.1 x 10(9) CFU Y. enterocolitica 0:3,
      (pYV+) and four days later with 1.1 x 10(9) CFU L. monocytogenes 4B. Clinical,
      paraclinical and morphological findings attending the infectious process were
      followed in dynamics up to the 28th day post infection (p.i.) with L.
      monocytogenes. The phagocyting activity of alveolar macrophages (aMa) was
      suppressed against Y. enterocolitica, in contrast to peritoneal macrophages (pMa)
      engulfing yersiniae more actively at the end of the study. Moreover, the tendency
      of augmented entering in both phagocytes of L. monocytogenes cells was well
      demonstrated, starting at the earlier intervals of examination. Histopathological
      studies showed a purulent meningoencephalitis and a catarrhal pneumonie, non
      reactive micronecroses in the spleen and lymphadenitis catarrhalis in the
      mesenteric lymph nodes. Analysis of the T-cell immune response (T-CIR) showed
      maximal values in the spleen lymphocytes after Y. enterocolitica and L.
      monocytogenes mixed infection. The B-CIR occurred early (at the 7th day p.i.) and
      was maximal at the 28th day p.i. in blood lymphocytes. The results obtained
      demonstrated that the mixed infection of guinea pigs with Y. enterocolitica and
      L. monocytogenes runs has a non lethal, generalized illness with a dominant role
      of L. monocytogenes cells.

PMID- 9916553
TI  - Infections and reinfections with avian pneumovirus subtype A and B on Belgian
      turkey farms and relation to respiratory problems.
AB  - A longitudinal study was performed on six turkey farms in order to determine
      whether infections with avian pneumovirus (APV) occur and if they are related to
      outbreaks of respiratory problems in Belgium. Blood was taken at 1-3 week
      intervals of 20 identified animals during the fattening period. On five farms,
      the turkeys seroconverted against APV shortly after the appearance of respiratory
      problems. On two farms, where the animals had not been vaccinated against APV,
      attempts were made to isolate APV during the outbreaks. Two isolates were
      obtained: one of subtype A, the other of subtype B. These results indicate that
      the respiratory problems on five farms were related to an infection with APV. A
      second increase in APV antibody titres detected on four farms at the end of the
      fattening period, indicates that reinfections frequently occur. This is, to our
      knowledge, the first report on the isolation of an APV subtype A on the
      continent.

PMID- 9916554
TI  - Diagnosis of Trypanosoma evansi in Saudi Arabian camels (Camelus dromedarius) by
      the passive haemagglutination test and Ag-ELISA.
AB  - The passive haemagglutination test and Ag-ELISA were employed to monitor antibody
      titres and antigenaemia levels in 4 Najdi camels experimentally infected with
      Trypanosoma evansi. The two tests were also used to determine the prevalence of
      trypanosomiasis in a total of 218 Najdi camels in the Gassim region, Central
      Saudi Arabia, during the period from October 1992 to September 1993. Trypanosoma
      evansi antibodies in the experimentally infected camels rose after 14-21 days and
      reached a maximum of between 1:64 and 1:128 by the 12th week post infection.
      Circulating antigens were detected in the experimentally infected camels one week
      post infection and antigenaemia levels fluctuated but generally remained above
      preinfection OD values. The results obtained from the field survey showed that
      5.5% of the sampled camels were parasitologically positive for trypanosomes,
      while 19.7% were serologically positive by the passive haemagglutination test and
      13.8% by Ag-ELISA. No significant age difference in seropositivity was observed
      in the tested camels.

PMID- 9916555
TI  - Age-related plasma chemistry findings in the buff-crested bustard (Eupodotis
      ruficrista gindiana).
AB  - Blood samples were obtained from adult (> 1.5 years) and juvenile (2-8 weeks, 9
      16 weeks and 17-24 weeks) captive buff-crested bustards (Eupodotis ruficrista
      gindiana) to study age-related changes. A total of twelve different tests were
      conducted using a Hitachi 90011 wet chemistry analyzer. A comparison of the
      values obtained was made between adult and juvenile buff-crested bustards and
      from the literature with other bustard species. Significant differences between
      adult and juvenile buff-crested bustards were found for glucose, uric acid, total
      protein, alkaline phosphatase, asparatate amino transferase and calcium. The
      results obtained from this study provide blood chemistry values for this species
      and demonstrate age-related differences between adult and juvenile birds.

PMID- 9916556
TI  - Heart-attack care: experience counts.

PMID- 9916557
TI  - A new approach to monitoring anticoagulation therapy: testing prothrombin time at
      home.

PMID- 9916558
TI  - Alcohol injections replace surgery for patients with hypertrophic cardiomyopathy.

PMID- 9916559
TI  - Greater potassium intake may lower stroke risk.

PMID- 9916560
TI  - Outlook for women after bypass surgery and angioplasty.

PMID- 9916561
TI  - Should three-drug therapy be standard for heart failure?

PMID- 9916562
TI  - Cardiology organizations issue guidelines on Viagra use.

PMID- 9916563
TI  - A recent article in the Harvard Heart Letter mentioned that the diuretic
      hydrochlorothiazide could cause impotence. My doctor has me on this medication.
      While it hasn't caused me any problems yet, I'm wondering what are the chances
      that it will?

PMID- 9916565
TI  - I like to run for exercise and fitness but have never been a speed demon. I used
      to run my four-mile route in 35 minutes, but since I started taking a beta
      blocker for high blood pressure, my time has stretched to more than 40 minutes.
      Should I stop taking this medication?

PMID- 9916564
TI  - After I had a heart attack and two bypass operations, I was put on Lipitor to
      lower my cholesterol. My cholesterol was never high--about 170-180 mg/dL. But my
      HDL was always low and triglycerides were somewhat high. Now my total cholesterol
      is 124 and my HDL has gone up slightly. My triglycerides are way down. My LDL
      cholesterol has fallen from 110 to 68. Is there any downside to such a low
      cholesterol level, other than the need to check my liver function tests?

PMID- 9916566
TI  - My doctor told me to check my heart rate when I feel certain symptoms, but I am
      embarrassed to say that I do not know how.

PMID- 9916567
TI  - I am 40 years old and use birth-control pills, but I have gotten nervous because
      some of my friends say this could cause heart attacks. It is dangerous for me to
      take the pill?

PMID- 9916568
TI  - I was recently diagnosed as having Graves' disease. It was undetected for a long
      time, and I know it can have effects on the heart. What should I be concerned
      about?

PMID- 9916569
TI  - A couple of years ago, I had a pacemaker put in. Now I am having some problems
      with dizzy spells. My doctor thinks these may be neurological and would like to
      do an MRI scan. However, he says that he can't because of my pacemaker. Is this a
      big problem? Is there anything that can be done about it?

PMID- 9916570
TI  - Nine suggestions for '99.

PMID- 9916571
TI  - Reversing skin aging.

PMID- 9916572
TI  - Managing pain.

PMID- 9916573
TI  - Hepatitis C.

PMID- 9916575
TI  - Conditioning by Pilates.

PMID- 9916574
TI  - Gender differences in disease.

PMID- 9916576
TI  - I recently read that potassium supplements can reduce blood pressure. What is
      your opinion? I have borderline hypertension, which I'm trying to control with
      diet and exercise.

PMID- 9916577
TI  - I have recently started taking Prempro (0.625 mg conjugated estrogens/2.5 mg
      medroxyprogesterone acetate). There is so much written about the benefits of
      taking estrogen, but I am wondering about the effects of the progesterone
      component. Will it counteract the benefits of estrogen?

PMID- 9916579
TI  - Arthritis 101: the class that relieves pain.

PMID- 9916578
TI  - A vital drug for heart attack patients.

PMID- 9916580
TI  - When alcohol and aging don't mix.

PMID- 9916581
TI  - Safe sex a must at any age.

PMID- 9916582
TI  - Can taking DHEA supplements prevent heart disease?

PMID- 9916583
TI  - My doctor prescribed Sinemet for my restless legs and it was a catastrophe. Why
      did you recommend it in a recent article?

PMID- 9916584
TI  - Choleresis induced by stimulation of the gastric antrum.

PMID- 9916585
TI  - Secretion of bile in response to food with and without bile in the intestine.

PMID- 9916586
TI  - The consumption of our heritage.

PMID- 9916587
TI  - Toward a better residency.
AB  - Residency programs can be improved by careful consideration of seven elements
      germane to resident life and education. A curriculum, the course of study, should
      be established. A balance between service and education must be maintained.
      Supervision by faculty and residents' willingness to be supervised ensures
      patient safety as well as teaching. Residents, faculty, and the program itself
      require frequent evaluation. A pleasant working environment is important.
      Sensitivity to issues of culture, gender, and ethnicity should be maintained by
      the program director, the faculty, and residents. Finally, the importance of
      stress in the lives of residents should be understood.

PMID- 9916588
TI  - Endosonography/bile drainage combination for difficult-to-diagnose gallbladder
      disease.
AB  - The diagnosis of cholecystitis and cholelithiasis is often straightforward,
      particularly when transabdominal ultrasound (TUS) reveals gallstones or other
      abnormalities of the gallbladder. There remain many patients, however, with
      typical biliary pain and normal findings on TUS. This latter group of patients,
      in which women constitute a large majority, often undergo considerable suffering.
      Their medical care can also be quite costly. Cholecystokinin cholescintigraphy
      and stimulated biliary drainage (SBD) have been proposed for difficult-to
      diagnose gallbladder disease, but they both have limitations. Cholecystokinin
      cholescintigraphy may not predict postoperative outcomes with a high degree of
      reliability. The processing and interpretation of bile drainage specimens is not
      standardized, and the sensitivity of SBD is less than that of endoscopic
      ultrasound (EUS). Combined endoscopic ultrasound and stimulated biliary drainage
      (EUS/SBD) offers a high degree of sensitivity in the diagnosis of cholecystitis
      and microlithiasis. Positive EUS/SBD is also highly correlated with long-term
      symptom resolution or relief following cholecystectomy.

PMID- 9916589
TI  - A randomized prospective controlled trial of laparoscopic extraperitoneal hernia
      repair and mesh-plug hernioplasty: a study of 315 cases.
AB  - Inguinal hernias can be repaired by traditional methods, tension-free, mesh-plug
      hernioplasty, and the less conventional laparoscopic techniques that have the
      added advantage of quicker recovery. Between September 1994 and September 1997, a
      prospective randomized controlled trial was performed on 292 patients with a
      total of 315 hernias. Of these, 150 patients with 169 hernias underwent the
      extraperitoneal laparoscopic repair (TEP) and 142 patients with 146 hernias were
      treated with mesh-plug hernioplasty. Patients were examined at 1 week after
      surgery and every 4 months thereafter for 3 years. Operative results,
      postoperative recovery, complications, and recurrences were recorded. Follow-up
      was complete for 89% of the patients. The average operative time was 31.5 minutes
      for the TEP and 30.5 minutes for the mesh-plug hernioplasty. The average
      operative time for the last 75 laparoscopic cases was 20 minutes, 10 minutes
      shorter than the open-surgery group. The overall recurrence rate was (2.5%) for
      the TEP and (3%) for the mesh-plug hernioplasty. Patients undergoing the
      laparoscopic repair consumed less narcotic analgesic and returned to their normal
      activity 1 week sooner than the open-surgery group. A median of 8 days vs. 15
      days was required for patients to return to work, respectively, in the TEP and
      open-surgery group (p<0.01). Intraoperative complications occurred in two
      patients (1.3%) in the TEP repair. Both had peritoneal tear that mandated
      conversion to the TAPP repair. There were no major postoperative complications. A
      total of 20 (13%) minor postoperative complications occurred in the TEP. Thirty
      three (23%) minor complications occurred in the open-surgery group (p<0.01).
      Ninety-eight percent of the patients were discharged the same day in the open
      surgery group compared to 100% in the laparoscopy group. Patients with inguinal
      hernias who undergo extraperitoneal laparoscopic repair have the same recurrences
      and hospital stay but recover more rapidly, consume less analgesic, and have
      fewer minor complications than those who undergo the mesh-plug hernioplasty.

PMID- 9916590
TI  - The value of intraoperative laparoscopic examination of the contralateral
      inguinal ring during hernia repair in children.
AB  - Approximately 40% of children with a clinical unilateral inguinal hernia display
      a patent processus vaginalis on the contralateral side; half of these children
      subsequently develop an inguinal hernia. The management of this problem is still
      controversial. Different strategies to identify patients who profit from an open
      contralateral exploration have been applied (diagnostic pneumoperitoneum,
      herniography, ultrasound). The purpose of this study was to evaluate the
      usefulness of intraoperative laparoscopy in a no-puncture technique through the
      opened hernia sack. In 75 children (age 6 months to 7 years) with clinical
      unilateral hernia laparoscopy (5-mm Laparoscope, 30 degrees and 70 degrees ), in
      cases of wide-open contralateral internal inguinal ring (Type III) an open
      surgical exploration was performed. Twelve patients (17%) fulfilled the
      laparoscopic criteria of a Type III ring. The diagnose was confirmed during open
      contralateral exploration. Seven children (8%) showed a patent but small
      processus vaginalis with a shallow internal ring. These patients were treated
      conservatively. In the follow-up period (median 6 months) one subsequent hernia
      developed. There was no technical failure, and no associated complications were
      seen. The median time for laparoscopy was 6 minutes. Intraoperative laparoscopy
      during unilateral hernia repair allows the identification of patients who profit
      from bilateral open surgery during the same operation with little additional
      operating time, and so far with no resulting complications. Application of this
      method may avoid a second hospitalization and operation as well as unnecessary
      routine bilateral open exploration. As an additional source of information
      through excellent visualization of the abdominal cavity, this method proved
      helpful to examine the incarcerated bowel after repositioning.

PMID- 9916591
TI  - Comparison of coagulation modalities in surgery.
AB  - The increase in laparoscopic surgery has resulted in an increased need for a safe
      and reliable method of obtaining minimally invasive operative hemostasis. Because
      the traditional "open" methods of controlling bleeding (pressure, tying, and
      suture ligating) are not as easily applied in the laparoscopic arena, a heavy
      reliance on forms of tissue and vessel coagulation is necessary. To better assess
      these forms, we compare monopolar, bipolar, and ultrasound energy, in addition to
      laser energy used in a novel application. In the first part, 20 rabbit mesenteric
      arteries that measured 1 to 1.5 mm in diameter were coagulated using each of the
      technologies. We measured the time to coagulation, the efficacy of hemostasis,
      lateral tissue damage, and local tissue temperature of the vessels when exposed.
      Part 2 consisted of a survival study using 12 New Zealand white rabbits. In each
      of these two groups splenectomies were performed. A laser-heated forceps was
      compared to a monopolar electrosurgery device for the speed of the operation,
      blood loss, and adhesion grade at necrosectomy. In addition, the speed to
      cauterization of the iliac vessels and the amount of tissue damage was measured.
      These vessels were also examined for the extent of microscopic damage. Bipolar
      electrosurgery was much slower than the other modalities, while monopolar
      electrosurgery caused significantly more tissue damage and elevation in lateral
      tissue temperature. The ultrasound technology and the laser-heated forceps were
      equally safe and efficacious instruments. There was no significant difference in
      the ability of the laser-heated forceps or the monopolar cautery to perform the
      splenectomy safely. However, the forceps cauterized the iliac vessels faster and
      with less lateral thermal injury than the ultrasound device. Although each
      instrument has its place in the surgical armamentarium, the ultrasound technology
      appears to be the safest and most efficacious commercially available device for
      obtaining hemostasis. The laser, as it is applied in this setting, was also
      highly effective, but still a prototype device.

PMID- 9916592
TI  - Endoscopic placement of nasoenteric feeding tubes in critically ill patients: a
      reliable alternative.
AB  - Spontaneous transpyloric passage of nasoenteric feeding tubes is often
      unsuccessful in critically ill patients due to gastric ileus. The purpose of this
      study was to evaluate the success rate of endoscopic placement of postpyloric
      nasoenteric tubes and the time required to achieve goal enteral nutritional
      support in critically ill patients with gastric ileus. Surgical ICU patients with
      gastric ileus, documented by recorded high gastric residual volumes via a
      nasogastric tube, were identified for placement of a nasoenteric postpyloric tube
      via esophagogastroduodenoscopy (EGD). EGD was performed bedside in the ICU, using
      intravenous sedation, for placement of a 43-inch (109 cm) 8 French tungsten
      weighted nasoenteric tube with an inner stylet into the duodenum, and the tube
      was advanced as far distally as possible. Abdominal radiograph was obtained to
      confirm final tube position postprocedure. Enteral feedings were initiated
      immediately with a full-strength formula and increased to the goal enteral
      feeding rate as tolerated. Thirty-four patients underwent successful placement of
      postpyloric nasoenteric tubes by EGD. One procedure was aborted in a patient with
      adult respiratory distress syndrome (ARDS) who developed hypoxemia with gastric
      insufflation during the EGD. The mean time to achievement of goal enteral
      nutritional support was 20.8 hours. Tubes remained in place for a range of 6 to
      37 days. Endoscopic placement of postpyloric enteral feeding tubes is highly
      successful, and allows for prompt achievement of goal enteral nutritional
      requirements. It has two main advantages: it eliminates the risk of patient
      travel to radiology for fluoroscopic placement, and allows for earlier initiation
      of enteral feedings because spontaneous passage of weighted nasoenteric tubes
      into the duodenum in critically ill patients is often unsuccessful.

PMID- 9916593
TI  - Does pneumoperitoneum cause bacterial translocation?
AB  - Although extensive research has been carried out on the respiratory and renal
      effects of intra-abdominal pressure increase, there is limited research with
      regard to its effects on bacterial translocation. The objective of this study was
      to discuss whether the high intra-abdominal pressure due to carbon dioxide (CO2)
      insufflation during laparoscopy leads to bacterial translocation. Eighteen male
      dogs, 7 of which constituted the control group, were used in the study. Two study
      groups, in which the intra-abdominal pressure was raised to 15 mm Hg and kept at
      that level for 30 and 120 minutes, respectively, were set. Blood gases and blood
      pressure values were observed throughout the experiments. Samples of peritoneal
      smear, portal vein blood, mesenteric lymph node, liver, spleen, and cecum were
      examined to detect bacterial translocation. Histopathological examinations of all
      samples were also carried out. No translocation was detected in the samples of
      peritoneal smear, portal blood, mesenteric lymph node, liver, or spleen, but in
      the samples of cecum, bacterial colonization for the second group (p<0.05) and
      for the third group (p<0.05) was significantly higher compared with the control
      group. There was a considerable difference between the second and third groups
      (p<0.05). The changes in the mesenteric lymph nodes were interpreted to be a
      result of bacterial drainage. Histopathological examination disclosed active
      changes in the mesenteric lymph nodes in all groups, but there was considerable
      sinus histiocytosis only in the third group. We conclude that the intraabdominal
      pressure of 15 mm Hg created by carbon dioxide insufflation does not lead to
      bacterial translocation but causes intraluminal bacterial colonization in the
      cecum after 30 minutes and after 2 hours.

PMID- 9916594
TI  - Laparoscopic esophagomyotomy without an antireflux procedure for the treatment of
      achalasia.
AB  - Various gastroenteric surgical procedures have been attempted laparoscopically.
      Laparoscopic esophagomyotomy (LE) with or without fundoplication, performed for
      achalasia, has gained popularity. In our clinic, LE (Heller's myotomy) was
      performed on six patients with achalasia. All patients underwent barium
      esophagography, endoscopy, and esophageal manometry for diagnosis. Extramucosal
      myotomy was started 6 cm above the cardioesophageal junction on the left
      anterolateral aspect of the esophagus and continued 1 cm below this area.
      Endoscopic control of the distal esophageal mucosa and the stomach was carried
      out under direct laparoscopic visualization following the completion of myotomy
      during the operation. LE was completed without complication in five patients. In
      one patient (16%), mucosal perforation occurred after myotomy during endoscopic
      control and was repaired with endostitches. There were no postoperative
      complications. The average hospital stay was 3 days. Three of the six patients
      agreed to 24-h pH monitoring, the results of which showed no evidence of reflux.
      All patients were completely symptom free in the postoperative period. The
      average preoperative lower esophageal sphincter pressure was 44 mm Hg, whereas in
      the early postoperative period and 6 months later, it was 11 mm Hg. There was no
      dysphagia or reflux esophagitis during the follow-up period (range 12 to 24
      months). LE is associated with low morbidity and a high success rate, comparable
      with an open procedure, and can be done without an antireflux procedure.

PMID- 9916595
TI  - Fibrinolytic activity in laparoscopic cholecystectomy.
AB  - The aim of this study was to examine the fibrinolytic activity in laparoscopic
      cholecystectomy (LC) to determine whether changes occur that might indicate a
      greater risk of thrombosis. The study was carried out in 20 patients who had
      undergone laparoscopic surgery for cholelithiasis without complications. The
      average age was 59.4 years (34-77 years). Seventy-five percent were women. The
      mean operating time was 70 minutes (35-120 minutes). Pneumoperitoneum at 14 mm Hg
      was maintained in all patients, and they were in 30 degrees reverse Trendelenburg
      position. Postoperative mobilization was obtained before 24 hours, and patients
      were discharged 48 hours after surgery. The control group was composed of 12
      patients, evenly distributed by age, sex, and length of surgery, who had
      undergone Bassini herniorrhaphy without complications or relapses. The following
      hemostatic parameters were studied: plasma fibrinolytic activity (PFA),
      euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator (t-PA),
      fast-acting plasminogen activator inhibitor-1 (PAI-1), and D-dimer (D-D). Samples
      were obtained at the following times: (1) under basal conditions the day before
      surgery, (2) preoperatively, (3) at the end of surgery, (4) 24 hours after
      surgery, and (5) on the seventh day following surgery. No patient had clinical
      manifestations of thromboembolic disease immediately after surgery or during an
      average follow-up period of 16 months (range 15-18 months). Analysis of the
      results of global fibrinolysis showed that fibrinolytic activity was enhanced
      only in the postoperative period (third sample) of the LC patients. The fraction
      of euglobulins enhances fibrinolytic activity in both groups in the third sample
      with regard to the other determinations; the LC patients showed a higher degree
      of significance (p<0.005). A significant increase of postoperative t-PA in both
      groups was found, being more significant in the LC group (p<0.005). In the PAI-1
      values, no significant differences existed between either determinations or
      groups. A significant increase in D-dimer (p<0.05) occurred in the immediate
      postoperative period (third sample) and 24 hours later (fourth sample), returning
      to normal basal values on the seventh day. No significant differences were found
      between the two groups. These results seem to indicate that LC produces an
      increase in the fibrinolytic activity in plasma as a result of the liberation of
      tissue plasminogen activator from the venous endothelium, which could indicate
      hypocoagulability during the immediate postoperative period and, therefore,
      signify less thrombotic risk for patients undergoing this procedure.

PMID- 9916597
TI  - Laparoscopically assisted percutaneous transperitoneal nephrolithotomy in pelvic
      dystopic kidneys: experience in 15 successful cases.
AB  - The stone-holding pelvic dystopic kidneys of 15 patients were treated with
      laparoscopically assisted percutaneous transperitoneal nephrolithotomy. With
      patients in the Trendelenburg position under laparoscopic control, the bowels
      were dislodged with forceps until the kidney became visible. Under simultaneous
      laparoscopic and fluoroscopic control, the nephrostomy track was created on the
      antegrade route using telescopic metal dilators and a rigid nephroscope.
      Percutaneous nephrolithotomy was carried out in the usual manner. All the stones
      could be removed successfully. The only minor complication was a delayed urine
      leakage through the abdominal drain in a patient with a double J stent. Severe
      complications did not occur. The average operating time was 55 (40-85) minutes;
      the average hospital stay was 4.8 (4-11) days. On the basis of the authors'
      experience and a literature review of cases of failed shock wave lithotripsy
      which is quite frequently unsuccessful in these cases-and cases of large, dense
      stones, this method appears to be the simplest and most suitable minimally
      invasive treatment of the stone-holding pelvic dystopic kidney.

PMID- 9916596
TI  - A comparative study of the analgesia requirements following laparoscopic and open
      fundoplication in children.
AB  - To introduce a new procedure, careful evaluation of its effects must be
      undertaken to assess its impact. Laparoscopic procedures in children are a
      relatively new phenomenon. A reduction in analgesia is a frequently quoted
      benefit of a laparoscopic procedure. The introduction of laparoscopic
      fundoplication into our surgical armoury lead us to evaluate the analgesia
      requirements of a laparoscopic procedure compared to conventional surgery.
      Comparative analysis of the analgesia requirements of 40 fundoplication
      procedures (20 laparoscopic, 20 open) was undertaken. All the pain-relief data
      was prospectively documented by a pain team as part of an ongoing hospital audit.
      This pain team was unaware of the comparative study, but were assessing the
      quality of analgesia within the hospital trust. The total amount of morphine
      analgesia required was similar for both laparoscopic and open surgery (0.432+/
      0.28, 0.427+/-0.28 mg/kg). The period for which analgesia was required was
      significantly less in the laparoscopic group (1.2+/-0.46, 2.7+/-0.67 days; p =
      0.03), yet the requirement for morphine during the first 24 hours was greater in
      the laparoscopic group (0.399+/-0.19, 0.22+0.11 mg/kg, p = 0.02) despite similar
      NSAID requirements (18+/-17.28, 18+/-20.16 mg/kg, respectively). The benefit of a
      laparoscopic over an open fundoplication would appear to be in the decreased
      duration of pain, as indicated by the decreased duration of analgesia following
      surgery.

PMID- 9916598
TI  - Video-assisted thoracoscopic left ventricular thrombectomy and coronary artery
      revascularization.
AB  - Advances in video-assisted techniques in the fields of general and thoracic
      surgery have led to the application of this technology in experimental and
      clinical cardiac surgery. Visualization of intracardiac anatomy and pathology
      allows procedures to be performed without violation of ventricular muscle, thus
      preserving myocardial function. We present the case of a patient with a recent
      myocardial infarction, found to have a large left ventricular thrombus on
      echocardiogram. By applying thoracoscopic surgical technology we successfully
      removed the thrombus during emergency coronary artery revascularization and
      avoided myotomy.

PMID- 9916599
TI  - Treatment of dyspepsia.
AB  - Dyspepsia is a condition that is commonly seen by family physicians and
      gastroenterologists in clinical practice. However, there is little consensus on
      how dyspepsia should be treated. Some of the issues that require consideration
      are: Who seeks medical help? What types of physicians do patients choose to see?
      Do different types of physicians see the same types of patients? Do different
      types of physicians treat dyspepsia differently? What causes dyspepsia? In
      addition, the definition of dyspepsia and the symptoms associated with it vary
      from region to region, creating problems when discussing these issues on an
      international basis. In this review, the above issues are discussed, with
      particular attention to the impact of Helicobacter pylori infection and gastric
      dysmotility. Recommendations for treatment are made, and predictions of how
      dyspepsia will be treated in the future are given.

PMID- 9916600
TI  - Guidelines for dyspepsia treatment in Japan.
AB  - Recently published guidelines for the treatment of dyspepsia have emphasized the
      importance of age, Helicobacter pylori infection, and alarm symptoms such as
      weight loss, anemia, and dysphagia in patient assessment. However, the currently
      available guidelines were not designed specifically for regions in which the
      incidence of gastric cancer is high, as is the case in Japan, and could lead to
      cases of gastric cancer being missed at a stage when they are treatable.
      Therefore a Japanese working group was organized to consider the design of
      dyspepsia treatment guidelines in Japan, with specific attention to the problem
      of gastric cancer and the lack of health insurance coverage for H pylori testing
      and eradication in Japan. To date, the group has prepared and tested clinically
      the feasibility of two drafts of the guidelines, and has incorporated a number of
      features and risk factors not currently included in other guidelines for
      dyspepsia treatment. This article describes the development of the guidelines and
      their provision of a rational basis for the management of patients with
      dyspepsia.

PMID- 9916601
TI  - Safety and efficacy of sildenafil citrate in the treatment of male erectile
      dysfunction.
AB  - Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective
      inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase
      type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus
      cavernosum. Chemically, it is a compound of the pyrazolo-pyrimidinyl
      methylpiperazine class. Sildenafil has no direct relaxant effect on human corpus
      cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus
      cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in
      this tissue. When sexual stimulation causes local release of NO, inhibition of
      PDE5 by sildenafil increases concentrations of cGMP in the corpus cavernosum,
      causing smooth muscle relaxation and blood flow into the penis, resulting in an
      erection. Sildenafil at recommended doses has no effect in the absence of sexual
      stimulation. The drug is rapidly absorbed after oral administration, with
      absolute bioavailability of 40%. Its pharmacokinetics are dose proportional over
      the recommended dosage range. Maximum plasma concentrations are reached within 30
      to 120 minutes after oral dosing in the fasting state. Sildenafil is cleared
      predominantly by the hepatic microsomal isoenzymes CYP3A4 (major route) and
      CYP2C9 (minor route). Clinical studies assessed the effect of sildenafil on the
      ability of men with erectile dysfunction to engage in sexual activity and,
      specifically, to achieve and maintain an erection sufficient for satisfactory
      sexual intercourse. Sildenafil was evaluated at doses of 25, 50, and 100 mg in
      randomized, double-masked, placebo-controlled clinical trials of up to 6 months'
      duration. The drug was administered to hundreds of patients aged 19 to 87 years
      having erectile dysfunction of various etiologies for a mean duration of 5 years.
      Sildenafil was associated with statistically significant improvement in erectile
      function compared with placebo. Adverse effects reported at a rate of >2% were
      headache, flushing, dyspepsia, nasal congestion, urinary tract infection,
      abnormal vision, diarrhea, dizziness, and rash. No cases of priapism were
      reported. The use of sildenafil is contraindicated in men who are taking organic
      nitrates, because of the potential for a precipitous decrease in blood pressure.
      Postmarketing reports and surveillance have revealed at least 39 deaths with
      sildenafil use in men having a history of heart disease, men taking nitrate
      medications, and men in poor physical health due to lack of exercise. Many of the
      men who experienced serious adverse effects or death had a variety of concomitant
      diseases and were taking multiple medications.

PMID- 9916602
TI  - Levofloxacin: a therapeutic review.
AB  - This therapeutic review discusses the pharmacology, pharmacokinetics, in vitro
      activity, drug interactions, and adverse effects of levofloxacin, a
      fluoroquinolone antibiotic. Particular emphasis is placed on the clinical
      efficacy of levofloxacin and its place in therapy. Compared with ciprofloxacin
      and the earlier quinolone agents, levofloxacin has an improved pharmacokinetic
      profile that allows convenient once-daily dosing in either an oral or parenteral
      formulation. Levofloxacin has enhanced activity against gram-positive aerobic
      organisms, including penicillin-resistant pneumococci. In published comparative
      trials involving commonly used treatment regimens, levofloxacin had equivalent if
      not greater activity in the treatment of community-acquired pneumonia, acute
      bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute
      pyelonephritis, and complicated urinary tract infection. Levofloxacin is well
      tolerated and induces minimal adverse drug reactions. Based on the above
      attributes, it may be reasonable to include levofloxacin on the hospital
      formulary in place of older quinolones. More recently released quinolones such as
      trovafloxacin exhibit similar advantages; however, until direct comparative
      trials between levofloxacin and these newer agents are conducted, it is difficult
      to advocate one agent over another. Regardless of which quinolone is the primary
      agent on the formulary, it is imperative that this class of antimicrobial drugs
      be used with discretion to minimize the development of resistance.

PMID- 9916603
TI  - Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for
      the treatment of human immunodeficiency virus infection.
AB  - Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor widely used
      in combination with other antiretroviral agents for the treatment of human
      immunodeficiency virus disease. To establish its safety profile, we conducted a
      review of data from prospective US and international clinical trials involving a
      total of 906 adult patients and 468 pediatric patients treated with NVP. Drug
      related adverse events were similar in adults and children, with rash and nausea
      most frequently reported in adults and rash and granulocytopenia most frequently
      reported in children. A separate analysis of rash based on data from adult
      patients in controlled trials demonstrated a 16% rate of NVP-attributable rash in
      these patients. Of patients with NVP-associated rash, 65% developed rash within
      the first 6 weeks of therapy, and it has been shown that a lower lead-in dose
      (200 mg/d vs the standard 400 mg/d) for the first 2 weeks of NVP treatment
      reduces the frequency of drug-associated rash. Serious rash (Stevens-Johnson
      syndrome [SJS] or SJS/toxic epidermal necrolysis transition syndrome) occurred
      with an incidence of 0.3% and clinical hepatitis with an incidence of 1.0% among
      NVP-treated patients in clinical trials. Adverse event data from long-term
      clinical trials demonstrated a lower incidence of NVP-related adverse events than
      in short-term trials of NVP therapy. An analysis of abnormal laboratory findings
      using thresholds similar to those found in the prescribing information for other
      commonly used antiretroviral agents and data from controlled trials in adults
      showed that the most frequently observed laboratory abnormalities were elevations
      in liver function test results. Approximately 50,000 patients in the United
      States had been treated with marketed NVP at the time of writing, and
      postmarketing surveillance has supported the overall safety profile observed in
      clinical trials. NVP has been shown to be well tolerated in both adult and
      pediatric patients.

PMID- 9916604
TI  - Use of midazolam in the treatment of refractory status epilepticus.
AB  - Status epilepticus is an epileptic seizure that lasts at least 30 minutes or is
      repeated at sufficiently brief intervals to produce a continued epileptic
      condition lasting a total of 30 minutes without the patient fully regaining
      consciousness. Various combinations of anticonvulsant agents, including
      benzodiazepines, phenytoin, and phenobarbital, have been used to manage this
      condition. However, at least 9% of patients with generalized convulsive status
      epilepticus do not respond to conventional first-line agents, and additional
      intervention is required. Refractory status epilepticus refers to sustained
      seizures that do not respond to initial drug therapy and persist longer than 60
      minutes. Reports on the response to first- and second-line agents suggest that
      the incidence of refractory status epilepticus is between 2000 and 6000 cases per
      year in the United States. Refractory status epilepticus is a major medical and
      neurologic emergency that requires immediate treatment to avoid significant
      morbidity and mortality. The anticonvulsive agent midazolam has proved to be
      effective, well tolerated, and fast acting when used to treat refractory status
      epilepticus in both adults and children. Its pharmacodynamic effects can be seen
      within 1 to 5 minutes of administration, and its anticonvulsive effects are
      apparent as early as 5 to 15 minutes after administration. This article reviews
      the pharmacology of midazolam and recent clinical reports on the drug's
      tolerability and effectiveness in the treatment of patients with refractory
      status epilepticus.

PMID- 9916605
TI  - Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II
      receptor blocker.
AB  - Predictable dose-related efficacy is considered to be an important attribute of
      any antihypertensive agent. To determine the magnitude of dose-responsive
      efficacy for valsartan, a highly selective angiotensin II-receptor blocker, we
      conducted an integrated analysis of efficacy data from nine double-masked,
      randomized, placebo-controlled, parallel studies of similar design and of at
      least 4 weeks' duration. The intent-to-treat analysis included 4067 patients with
      mild-to-moderate hypertension who had received valsartan (n = 2901) 10, 20, 40,
      80, 160, or 320 mg once daily or placebo (n = 1166). Blood pressure was assessed
      at trough (24 hours after the last dose). In all nine studies, valsartan doses >
      or = 80 mg produced statistically significant reductions in supine or seated
      diastolic blood pressure (SDBP) and systolic blood pressure (SSBP) compared with
      placebo (P < 0.05). The integrated analysis demonstrated a clear increase in
      blood-pressure-lowering efficacy with increasing dose across the range 10 to 320
      mg (placebo-subtracted mean changes from baseline to end point for valsartan 10,
      20, 40, 80, 160, and 320 mg, respectively: SDBP, -0.8, -2.8, -2.6, -3.9, -5.1,
      and -6.4 mm Hg; SSBP, -1.3, -5.7, -5.3, -6.8, -8.6, and -9.0 mm Hg). The data
      demonstrate that valsartan provides dose-responsive antihypertensive efficacy
      across the therapeutic dose range, with clinically relevant blood-pressure
      lowering at doses > or = 80 mg once daily.

PMID- 9916606
TI  - Efficacy and tolerability of cefprozil versus amoxicillin/clavulanate for the
      treatment of adults with severe sinusitis.
AB  - Cefprozil is a beta-lactamase-stable oral cephalosporin with an antimicrobial
      spectrum that includes gram-positive and gram-negative pathogens commonly
      associated with acute bacterial sinusitis, one of the most common upper
      respiratory tract infections among adults. We conducted a multicenter, open-label
      study to compare the efficacy and safety of cefprozil and amoxicillin/clavulanate
      in the treatment of adults with severe acute bacterial sinusitis diagnosed by
      clinical and radiographic criteria. A total of 278 patients entered the study,
      140 (59 males, 81 females) in the cefprozil group and 138 (69 males, 69 females)
      in the amoxicillin/clavulanate group. Patients were randomized to 10 days of
      treatment with either cefprozil 500 mg BID or amoxicillin/clavulanate 500 mg/125
      mg TID. Clinical severity was assessed at study entry, and patients were
      stratified based on symptom grade. Efficacy was evaluated using a 10-point
      questionnaire administered during, at the end of, and 2 weeks after completing
      therapy. At the end of treatment, 84.5% (71/84) of patients with severe sinusitis
      treated with cefprozil had a satisfactory clinical response, which was not
      significantly different from the 89.9% (80/89) of patients in the
      amoxicillin/clavulanate group who had a satisfactory clinical response. Two weeks
      after completing treatment, 80.8% (63/78) of cefprozil-treated patients and 81.0%
      (64/79) of amoxicillin/clavulanate-treated patients with severe sinusitis had a
      satisfactory response. Relapse was more common among amoxicillin/clavulanate
      patients (6/70; 8.6%) than among cefprozil patients (2/65; 3.1%), but the
      difference was not statistically significant. Significantly more
      amoxicillin/clavulanate-treated patients experienced adverse events compared with
      cefprozil-treated patients (P < 0.001), including diarrhea (P < 0.001), nausea (P
      < 0.042), and rash (P < 0.035). Three times as many amoxicillin/clavulanate
      patients discontinued treatment because of adverse events. Cefprozil demonstrated
      comparable clinical efficacy to amoxicillin/clavulanate in the treatment of
      adults with severe sinusitis; however, cefprozil was associated with a
      significantly lower incidence of diarrhea, nausea, and rash.

PMID- 9916607
TI  - Efficacy, tolerability, and effects on quality of life of inhaled salmeterol and
      oral theophylline in patients with mild-to-moderate chronic obstructive pulmonary
      disease. SLMT02 Italian Study Group.
AB  - The aims of management in mild-to-moderate stable chronic obstructive pulmonary
      disease (COPD) are to improve symptoms and quality of life (QOL), reduce decline
      in lung function, prevent and treat complications, increase survival while
      maintaining QOL, and minimize the adverse effects of treatment. Bronchodilator
      therapy is the keystone of improving COPD symptoms and functional capacity. The
      primary objective of this open-label study was to compare the efficacy and
      tolerability of salmeterol 50 microg BID administered by metered-dose inhaler
      versus oral, titrated, sustained-release theophylline BID, both given for 3
      months to patients with a clinical history of chronic bronchitis. The secondary
      objectives of the study were to evaluate the safety profile of the two drugs for
      an additional 9-month period and to assess changes in QOL both within and between
      treatment groups, using the 36-Item Short Form (SF-36) Health Survey. One hundred
      seventy-eight outpatients (122 men, 56 women; mean age, 56 +/- 12.9 years; mean
      body weight, 76.1 +/- 11.8 kg) were randomized to the two treatment groups.
      Patients receiving salmeterol showed significant improvement in mean morning peak
      expiratory flow rate (16.56 L/min) over the 3-month period compared with patients
      receiving theophylline (P = 0.02). Salmeterol also significantly increased the
      percentage of symptom-free days and nights with no additional salbutamol
      requirement (P < 0.01). A significant difference was found between increases in
      forced expiratory volume in 1 second compared with baseline for salmeterol
      compared with theophylline throughout the initial 3-month period (0.13, 0.16, and
      0.16 L at months 1, 2, and 3, respectively) and during the additional 9 months.
      The incidence of adverse events was similar in the two groups (salmeterol, 49.5%;
      theophylline, 49.4%), with a lower percentage of pharmacologically predictable
      adverse events in patients receiving salmeterol (4%) compared with those
      receiving theophylline (14.8%). Both drugs improved QOL, as measured by effects
      on the eight aspects of life experience analyzed by the SF-36 questionnaire.
      Salmeterol therapy was effective in more aspects, and the improvements seen in
      each were numerically greater than those seen with theophylline therapy.
      Statistically different changes between the two treatment groups were reported
      for physical functioning, changes in health perception, and social functioning (P
      = 0.02, P = 0.03, and P = 0.004, respectively). These data suggest that inhaled
      salmeterol 50 microg BID was more effective and better tolerated than oral,
      titrated theophylline and allowed better long-term control of airways obstruction
      and symptoms with improved lung function in patients with COPD.

PMID- 9916608
TI  - Effect of Maalox on the oral absorption of sparfloxacin.
AB  - Sparfloxacin is a broad-spectrum oral fluoroquinolone antimicrobial agent with a
      long elimination half-life (t(1/2)). Concurrent treatment with antacids has
      demonstrated a reduction in the oral absorption of many quinolones. This study
      was undertaken to determine an optimal time for dosing antacids in relation to
      sparfloxacin administration to minimize antacid-induced reduction in sparfloxacin
      bioavailability. This open-label, single-dose, randomized, four-way crossover
      study was conducted in 20 healthy male volunteers between the ages of 18 and 38
      years. Treatments consisted of single 400-mg oral doses of sparfloxacin alone and
      with Maalox 30 mL given 2 hours before, 2 hours after, and 4 hours after oral
      administration of sparfloxacin. All 20 subjects completed the study. A 400-mg
      single oral dose of sparfloxacin was well tolerated both given alone and with
      Maalox. Maalox given 4 hours after sparfloxacin administration was the only
      regimen that did not cause a statistically significant reduction in the rate and
      extent of sparfloxacin absorption. The 90% confidence intervals comparing
      sparfloxacin alone with the preceding regimen in terms of area under the
      concentration-time curve from zero to infinity (AUC(0-infinity)) and maximum
      plasma concentration (Cmax) were within the range 80% to 125%. Administration of
      Maalox 2 hours before, 2 hours after, and 4 hours after sparfloxacin caused mean
      decreases in AUC(0-infinity) of 23%, 17%, and 5%, respectively. Corresponding
      decreases in mean Cmax values were 29% with Maalox administered 2 hours before
      sparfloxacin and 13% with Maalox administered 2 hours after sparfloxacin. The
      mean Cmax value was un affected when Maalox was administered 4 hours after
      sparfloxacin administration. The 90% confidence intervals for these comparisons
      with sparfloxacin alone were outside the 80% to 125% range and did not include
      100%. Time to Cmax and t(1/2) were similar for all four regimens. The elimination
      rate of sparfloxacin was unaffected by concomitant administration with Maalox in
      healthy male volunteers.

PMID- 9916609
TI  - Amlodipine, felodipine, and isradipine in the treatment of Chinese patients with
      mild-to-moderate hypertension.
AB  - Optimal treatment of hypertension requires the use of effective antihypertensive
      drugs. Calcium channel blockers are widely used in the treatment of hypertension
      and appear to be particularly efficacious in ethnic Chinese patients. The aim of
      this open-label study was to prospectively investigate the efficacy and
      tolerability of three dihydropyridine calcium channel blockers in sequence, using
      the same protocol for each. After 2 weeks of placebo treatment, 73 males and 45
      females (mean age, 45 +/- 10 years; mean weight, 67 +/- 10 kg) with essential
      hypertension (diastolic blood pressure, 95 to 115 mm Hg) were treated with
      amlodipine (n = 41), felodipine (n = 38), or isradipine (n = 39) for 8 weeks,
      with dose titration after 4 weeks. Mean seated systolic and diastolic blood
      pressure decreased by 23/17, 30/17, and 20/15 mm Hg after 8 weeks of treatment
      with amlodipine, felodipine, and isradipine, respectively. These reductions were
      all statistically significant. Blood pressure was controlled (defined as
      diastolic pressure < 90 mm Hg at the final visit or a decrease from baseline of >
      or = 10 mm Hg) in 85%, 74%, and 74% of patients receiving amlodipine, felodipine,
      and isradipine, respectively. There were no significant changes in heart rate,
      plasma lipid levels, or serum biochemistry markers with any of the three
      treatments. No serious adverse events occurred, but mild adverse effects,
      including headaches, flushing, tachycardia, dizziness, and edema, were reported;
      1 (2%), 6 (16%), and 5 (13%) patients receiving amlodipine, felodipine, and
      isradipine, respectively, withdrew from the study (P < 0.05). The results of this
      study indicate that all three drugs are highly effective in lowering blood
      pressure and are well tolerated in Chinese patients with mild-to-moderate
      hypertension.

PMID- 9916610
TI  - Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution
      QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle
      glaucoma or ocular hypertension.
AB  - We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5%
      QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in
      intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The
      study had a positive-controlled, double-masked, randomized, multicenter, 12-week,
      two-period (6 weeks each), crossover design. One hundred fifty-two patients with
      open-angle glaucoma or ocular hypertension were randomized to receive either
      timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed
      by a crossover to the alternate treatment. IOP and heart rate were measured at
      morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming
      solution QD was comparable to levobunolol BID in reducing IOP at peak and trough.
      Although the effects on peak heart rate were similar between the two medications,
      the effect on trough heart rate of timolol maleate gel-forming solution QD was
      significantly less than that of levobunolol BID (P = 0.001). The incidence of
      ocular burning and stinging was comparable between the two treatments. Patients
      experienced significantly more blurred vision when using timolol maleate gel
      forming solution than when using levobunolol (P = 0.013). Overall, more patients
      experienced at least one adverse event when using timolol maleate gel-forming
      solution. Timolol maleate gel-forming solution QD is as efficacious in reducing
      IOP as levobunolol BID.

PMID- 9916611
TI  - In vitro activity of grepafloxacin and 25 other antimicrobial agents against
      Streptococcus pneumoniae: correlation with penicillin resistance.
AB  - Strains of Streptococcus pneumoniae from the United States that were susceptible,
      intermediately resistant, or highly resistant to penicillin were tested for
      susceptibility to 26 antimicrobial agents that have been used or considered for
      the treatment of patients with pneumococcal infections. The drugs tested included
      penicillins, one penicillin/beta-lactamase inhibitor combination, cephalosporins,
      macrolides, a lincosamide, fluoroquinolones, and four miscellaneous drugs
      (vancomycin, rifampin, tetracycline, and trimethoprim-sulfamethoxazole). The
      activities of the penicillins and macrolide agents were similar, but the
      activities within the cephalosporin and fluoroquinolone classes were often
      dissimilar. For the fluoroquinolones, the order of in vitro activity, from most
      to least active, was grepafloxacin, sparfloxacin, levofloxacin, ciprofloxacin,
      and ofloxacin. Increased resistance to penicillin in the pneumococcal isolates
      studied correlated with increased resistance to other penicillins,
      cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim
      sulfamethoxazole but did not correlate with increased resistance to the
      fluoroquinolones, rifampin, or vancomycin. These findings may be helpful to
      health professionals selecting empiric therapy for respiratory tract infections
      involving S. pneumoniae.

PMID- 9916612
TI  - Emerging standardization in pharmacoeconomics.
AB  - In this study, we reviewed pharmacoeconomic guidelines from the United Kingdom,
      Spain, Italy, Australia, Canada, and the United States to determine areas of
      emerging standardization. We examined the published literature, publication
      guidelines of major health journals, and published and unpublished
      recommendations from various task forces and conferences on related topics. The
      review revealed several general principles for which there was consensus across
      guidelines. These common features included the importance of using and reporting
      transparent methods so that readers can easily understand what calculations are
      being performed on which data elements, minimizing bias, and providing
      justification for the methods and assumptions used. Differences were detected
      across guidelines on the following topics: type of pharmacoeconomic assessment,
      perspective, comparators and data sources, data analysis, cost analysis, future
      cost analysis, outcomes assessment, modeling, time horizon, discounting,
      disclosure, and generalizability. Evolution of economic guidelines hinges on
      whether the primary goal is to increase the consistency or increase the validity
      of economic assessments. Some balance between these two objectives is desirable.

PMID- 9916613
TI  - Drug utilization patterns and outcomes associated with in-hospital treatment with
      risperidone or olanzapine.
AB  - This study compared the drug-utilization costs and indicators of clinical
      outcomes associated with the use of risperidone and olanzapine in a hospital
      setting. We conducted a nonrandomized, retrospective chart review of consecutive
      patients identified as presenting with psychotic symptoms on inpatient wards at
      Riverview Hospital in British Columbia and given either risperidone or olanzapine
      as their first new drug after reassessment (n = 30 per treatment group). Data
      were collected for up to 120 days. No significant differences were observed
      between groups in terms of sex, age, duration of illness, or diagnosis. The mean
      dosage of risperidone for responders was 4.89 +/- 2.56 mg/d, whereas that for
      olanzapine was 17.19 +/- 3.88 mg/d. The associated daily drug-acquisition costs
      were significantly different, at CA$4.69 for risperidone and CA$11.52 for
      olanzapine. Notes in patient charts indicated that a significantly greater
      proportion of risperidone-treated patients (60.0%) than olanzapine-treated
      patients (26.7%) responded to therapy, as indicated by improvement in at least
      one target symptom (P < 0.01). Forty percent of patients initially treated with
      risperidone were discharged on their original therapy, compared with 13.3% of
      patients treated with olanzapine (P < 0.05). These results were not substantially
      affected by correction for markers of illness severity or treatment resistance.
      Overall, no significant differences in side effects were recorded in the patient
      records of the two groups. Within this cohort of patients, risperidone treatment
      was associated with lower drug-acquisition cost and better treatment outcomes
      than olanzapine.

PMID- 9916614
TI  - Economic and gastrointestinal safety comparisons of etodolac, nabumetone, and
      oxaprozin from insurance claims data from patients with arthritis.
AB  - This study was conducted to compare the effect of etodolac, nabumetone, and
      oxaprozin use on gastrointestinal (GI) safety and associated costs based on
      insurance claims information from practice settings. Data were obtained from a
      national claims database (MarketScan) for the years 1992 to 1994. The claims data
      of interest were for patients with arthritis who had used etodolac, nabumetone,
      or oxaprozin exclusively during a 9-month follow-up period (ONLY groups), or
      these drugs plus (PLUS groups) the other nonsteroidal anti-inflammatory drugs
      (NSAIDs) ibuprofen, naproxen, diclofenac, sulindac, piroxicam, ketoprofen, or
      indomethacin. For each group, we obtained information on the use of inpatient and
      outpatient services for GI-related events and the associated costs. All GI
      admissions were classified as NSAID-induced or possibly NSAID-induced events
      based on International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9 CM) codes. All outpatient upper GI ulcers or bleeding
      episodes were also identified by specific ICD-9 CM code. There were no
      significant between-group demographic differences. The proportions of patients
      with NSAID-induced and possibly NSAID-induced GI admissions were 0.1% and 0.4%
      for the etodolac-ONLY, 0.3% and 1.0% for the nabumetone-ONLY, and 0.1% and 0.5%
      for the oxaprozin-ONLY groups, respectively (P > 0.05), and a similar pattern was
      observed among the PLUS groups. In outpatient settings, 3.9%, 4.2%, and 4.9% of
      the etodolac-, nabumetone-, and oxaprozin-ONLY patients, respectively (P > 0.05),
      and 6.0%, 5.3%, and 4.7% of the etodolac-, nabumetone-, and oxaprozin-PLUS
      patients, respectively, had at least one upper GI ulcer/bleeding claim (P >
      0.05). The total health care costs for 9 months were approximately $3000 each for
      the etodolac-, nabumetone-, and oxaprozin-ONLY groups. Oxaprozin, nabumetone, and
      etodolac had similar GI-safety and associated-costs profiles based on information
      from practice settings. Also, in patients who used multiple NSAIDs, the groups
      did not differ in their GI-safety and cost profiles.

PMID- 9916615
TI  - Pharmaceuticals and medicare managed care: pharmacoeconomic considerations.

PMID- 9916616
TI  - Medicare managed care: past, present, and future.
AB  - Medicare managed care enrollment has mushroomed in the past few years, tripling
      from 1993 to 1997. The payment rates have allowed plans to offer valuable extra
      benefits to beneficiaries at little or no additional cost; employers have
      provided inducements for their retirees to enroll; and many of the new Medicare
      beneficiaries are already in managed care plans when they enter the program. The
      Balanced Budget Act of 1997 and other factors could cause enrollment trends to
      change in either direction. More kinds of plans, including physician service
      organizations and preferred provider organizations, may be more attractive; new
      educational efforts may make more beneficiaries aware of managed care plans; and
      employers may continue to move their retirees into managed care. On the other
      hand, lower than expected Medicare payment rates to the plans may reduce the
      additional benefits they offer; consumer dissatisfaction with managed care is
      growing; and employers are dropping retiree benefits altogether. The future of
      Medicare managed care is hard to predict.

PMID- 9916617
TI  - Medicare managed care: budgetary and tax implications.
AB  - The Medicare program is in precarious financial condition because of underfunding
      and structural defects in the way it pays providers of medical care. Given the
      prevailing anti-tax sentiment, the more promising route for attaining Medicare
      fiscal solvency would seem to lie on the expenditure side of the equation. This
      paper proposes a managed care model for reform that relies on an efficient and
      already-tested form of competitive bidding for the provision of medical care. It
      concludes with a discussion of short-run, intermediate-run, and long-run
      budgetary and tax implications for the Medicare program.

PMID- 9916618
TI  - Medicare managed care: consumers' perspectives.
AB  - The 1997 CareData survey of members of Medicare risk health maintenance
      organizations (HMOs) measured the degree of satisfaction of Medicare managed care
      members with emphasis on pharmacy-related issues and specific disease treatment
      perceptions. The survey was a 12-page, self-administered questionnaire assessing
      more than 150 issues; it was distributed to 23,140 known enrollees of Medicare
      risk HMOs by their former employers between May and July 1997. A total of 12,265
      Medicare beneficiaries enrolled in more than 70 major health plans in 23 US
      geographic markets completed and returned their questionnaires (response rate,
      53%). The pharmacy benefit was cited by 75% of the respondents as the reason for
      joining their plan; 81% of the respondents reported being highly satisfied with
      the pharmacy benefit overall, with regional variations from a low of 60% to a
      high of 82%. The issues driving enrollees' satisfaction after being in their plan
      for a minimum of 6 months and a mean length of slightly more than 3 years were:
      satisfaction with customer service and plan administration (11.6% explained
      variance); the plan's concern for the member's well-being (10.6%); the belief
      that the care improved the member's health and well-being (9.2%); satisfaction
      with choice of specialists (5.3%); satisfaction with the pharmacy plan (5.1%);
      and satisfaction with the primary care physician (4.8%). Significant variations
      were seen among regions, plans, and the self-reported health status of the
      respondents.

PMID- 9916619
TI  - Prescription drug formularies in managed care: concerns for the elderly
      population.
AB  - Prescription drug formularies are a key element in the rapidly growing trend of
      prescription drug benefit management. The use of formularies can increase the
      quality of prescribing and reduce the costs of prescription drug therapy. This is
      particularly important to older Americans, who represent about 13% of the
      population but consume roughly one third of the drugs prescribed in the United
      States. However, the question of whether the use of formularies affects patient
      access to pharmaceuticals has not been analyzed sufficiently. This paper
      identifies benefits and risks to older Americans from the use of prescription
      drug formularies by third-party payers, analyzes the evidence of those benefits
      and risks, and proposes areas for future research. An extensive review and
      synthesis of the literature were performed, focusing on three aspects of drug
      formulary design: (1) the extent to which health maintenance organizations and
      insurers consider consumer interests when using formularies; (2) the extent to
      which formulary design is affected by clinical and economic considerations; and
      (3) the impact of formularies on the quality of drug care received. Safeguards to
      guarantee that economic considerations of drug benefit managers do not restrict
      access to needed drugs are insufficient. Alternatively, no evidence to date shows
      that the use of formularies adversely affects patients' access to pharmaceutical
      care. More research is required to understand the process of drug formulary
      development and the extent to which different formulary recommendations impede on
      physicians' ability to provide high-quality care.

PMID- 9916620
TI  - Medicare managed care: policy concerns.
AB  - This paper briefly reviews the extent of current drug coverage for Medicare
      beneficiaries and describes the most important issues faced by aged beneficiaries
      who receive or seek drug coverage through a Medicare managed care plan. Changes
      in payment rates to these plans as a result of the Balanced Budget Act of 1997
      may result in plans reducing or eliminating drug coverage. Under current law
      beneficiaries in these plans will have severely limited options for replacing
      drug coverage; as a result, many will not be able to obtain this coverage either
      through Medigap or previous retiree coverage. In the absence of any change in
      current law, one approach to addressing these issues is to refocus Medicare
      managed care plans on managing the total cost of caring for patients over time
      and across settings. Only through such an integrated approach will Medicare
      managed care plans have the tools to function within the new payment rates and
      realize the value of the pharmaceutical benefit to the plan and the patients.

PMID- 9916621
TI  - Cytokines in GvH and GvL.

PMID- 9916622
TI  - High-dose chemotherapy for salvage treatment of germ cell tumors: Charite,
      Virchow Klinikum, Berlin.

PMID- 9916623
TI  - Treatment of mycotic infections after haemopoietic progenitor cell
      transplantation with liposomal amphotericin-B.
AB  - 115 patients undergoing allogeneic or autologous bone marrow or peripheral blood
      stem cell transplantation were treated empirically or for documented fungal
      infection with liposomal amphotericin-B in doses up to 10mg/kg bodyweight for a
      duration up to 61 days. The therapy was excellent tolerated and clinical side
      effects occurred in only eight patients. The drug had to be withdrawn in one
      episode. A significant influence of liposomal amphotericin-B on laboratory
      parameters was not observed. Creatinine increased under therapy from a median
      base point of 1,0 (0,2-3,5) mg/dl to the upper normal value of 1,4 (0,4-4,2)
      mg/dl. Heavy increases of creatinine as well as of bilirubin, OT and PT were
      mostly associated with GvHD or regimen related toxicity. Considering the high
      risk state of the patients the overall response rate was favourable with 62,9%.
      However, despite administration of liposomal amphotericin-B culture-proven
      mycoses were associated with a high morbidity (93,3%). Only one of fourteen
      patients was cured from Candida lambica septicaemia. We conclude that the
      antimycotic therapy with liposomal amphotericin-B has a low incidence of side
      effects. This should, considering the high mortality of fungal infections in BMT
      recipients, encourage investigators to perform dose escalating studies against
      the conventional formulation.

PMID- 9916624
TI  - The sixth quality control exercise of the Central European tissue typing
      laboratories.

PMID- 9916625
TI  - Results of evaluation of the quality of HLA typing in the Czech Republic.

PMID- 9916626
TI  - Our experiences with 1D-IEF in selection of bone marrow donors.

PMID- 9916628
TI  - Implication of molecular analysis of HLA-A*02 subtyping for unrelated bone-marrow
      donor selection.
AB  - The HLA-A*02 allele is the most heterogeneous allele at HLA-A locus with 22
      different subtypes so far identified. All of these subtype polymorphisms are
      located in alpha 1 and alpha 2 domains which are responsible for peptide biding
      and HLA restricted recognition by T-cell receptor. The aim of the present study
      was to determine the frequency of different HLA-A*02 alleles in 33 healthy
      unrelated Croatians. HLA-A*02 subtyping has also been retrospectively performed
      in 2 recipient-unrelated donor pairs and in 4 recipient-HLA phenotypically
      identical parent pairs. All subjects, previously typed as HLA-A2 by serology were
      tested using HLA-A*02 ARMS-PCR kit which discriminates 17 different A*02 alleles.
      Among 17 A*02 alleles we have found 4 different A*02 subtypes in healthy
      unrelated Croatians. The most frequent A*02 allele was A*0201 (84%). The
      frequency of the remaining A*02 alleles were as follows: A*0205 (3%), A*0207 (6%)
      and A*0213 (6%). Among 6 tested bone-marrow transplantation (BMT) pairs, only one
      has been found to be A*02 subtype incompatible (A*0201/A*0205). Four different
      A*02 alleles are found in Croatian population with the predominance of A*0201.
      However these results suggest that A*02 subtyping is also necessary for optimal
      matching of HLA-A*02 positive donor-recipient pairs in HLA incompatible BMT.

PMID- 9916627
TI  - Class I typing by PCR-SSP in Olomouc.
AB  - In this article, methodical experience and population data are given for
      application of PCR-SSP/ARMS method (Phototyping) to HLA class I typing in
      Olomouc. Phototyping is reliable method suitable for typing of small to medium
      number of samples. Method is fast enough for use in on-call service, resolution
      is better than the level of good serology, and price of method is comparable with
      serology. Our experience and tips are described below. Population data of healthy
      unrelated individuals for HLA-A, -B, -Cw are given in the tables.

PMID- 9916629
TI  - Molecular typing of HLA class I and class II for a transplantation programme.

PMID- 9916630
TI  - Influence of HLA-DPB1 mismatches on MLR responses: the role of high resolution
      HLA class II typing and MLC in unrelated donor selection for BMT.
AB  - Twenty eight Hungarian patients lacking a compatible related donor and their 61
      HLA-A,B,DR serologically identical potential unrelated donors (selected from
      BMDW) were investigated in this study. Out of the 61 donor-recipient pairs only 7
      (11,5%) proved to be HLA-identical at DNA level. Thirty one pairs (50,8%)
      differed in DP alleles, 1 pair (1,6%) has a DQ mismatch only and 22 (36,1%) pairs
      differed in more alleles. More than one potential donor was found for 26 patients
      and 5 of them have several donors with DP mismatches only. Among the 31 donor
      recipient pairs differing only in DP alleles, 0, 1 and 2 mismatches were observed
      in GvH direction in 7, 10 and 14 cases, respectively. In the MLC assay no
      proliferative response was observed when no DP mismatch has been found. Among the
      1 and 2 DP mismatched cases 11 (35,5%) gave negative and 13 (41,9%) gave positive
      MLR results. We have found a large scatter in RR values. On the basis of the DNA
      typing and MLR results we have found that HLA-DPB1*0101-0201 stimulator-responder
      combination always gave negative MLR in both direction. HLA-DPB1*0201-0301 and
      DPB1*0301-0401 allele combinations were reactive in all cases. In conclusion MLC
      assay might indicate the low immunogeneicity in certain DP allele combinations as
      well as the avoidable positive combinations, which may help to select the best
      fitting donor for BMT.

PMID- 9916631
TI  - Hungarian Bone Marrow Donor Registry: present status and activity.

PMID- 9916632
TI  - An overview of the Czech Bone Marrow Donor Registry.
AB  - The Czech Bone Marrow Donor registry (CBMD) was founded in 1991 in the National
      HLA centre at Prague's Institute for Clinical and Experimental Medicine. In the
      same year, the CBMD submitted its data to the Bone Marrow Donors Worldwide
      (BMDW). Another line of CBMD's international cooperation is accomplished through
      computer linkup with the European Donor Secretariat (E.D.S) network. Donors are
      being recruited constantly through blood transfusion units and other volunteers
      are enrolled through the mass media. All the methodology used is developed in
      compliance with the standards of the European Federation for Immunogenetics
      (EFI). CBMD closely cooperates with clinical centres for transplantation of bone
      marrow, stem cells (PBSC) and cord blood from unrelated donors. More than 7,000
      potential bone marrow typed in HLA-A, B locus have been registered. Besides
      potential bone marrow donors, frozen cells of cord blood are kept by CBMD. Search
      requests from registries all over word come via E.D.S. daily except for weekends.
      Since its foundation in 1991, nearly 20,000 international requests have been
      handled. During the last two years, 5 CBMD donors provided their bone marrow to
      Czech patients, one donor provided stem cells (PBSC) and one donor provided bone
      marrow + stem cells (PBSC). To date, more than 20 transplantations from unrelated
      donors have been performed in Prague's transplant centres.

PMID- 9916633
TI  - Confirmatory typing results of the National Polish Bone Marrow Donors Registry.
AB  - Preliminary analysis of HLA class I typing of 618 individuals (patients and
      healthy members of 153 families) referred to the National Polish Bone Marrow
      Donors Registry (NPBMDR) for a donor search revealed that the number of
      undetected locus A and B antigens was more frequent than it was reported in a
      large scale population study in Poland (0.28 vs 0.076, p=0.000). This was
      associated with a lack of typing of family members for 51 out of 153 patients.
      171 individuals primary typed (140 by serology and 31 by DNA typing) in 6
      different Polish institutions were retyped in our laboratory with the use of PCR
      SSO or PCR-SSP techniques. The results were discrepant in 50 cases (29%)
      including 19 patients and 31 family members. In 46% one DR specificity was
      missing, false typing of one or two specificities was evident in 46% and 14% of
      erroneous typing, respectively. The highest rate of errors was found in DRw52
      group of specificities with the most difficult DR13 (32% of all false typing and
      67% of errors within DRw52 group).

PMID- 9916634
TI  - Serological versus molecular HLA-DR typing of cadaveric donors in conditions of
      Regional Tissue Typing Laboratory.
AB  - DNA typing for HLA class H presents quality typing which improves kidney graft
      survival. Discrepancy between serological and molecular biological typing of
      major histocompatibility complex varies from ten to fifteen percent according to
      the European Tissue Typing Laboratories. In conditions of Regional Tissue Typing
      Laboratory we started with molecular HLA-DR typing in the beginning of 1997. One
      of the reasons was large activity of Regional Transplantation Centre in
      University Hospital and as we mentioned before quality of molecular HLA typing.
      Till November 1997 we took and typed 43 donors organs and we transplanted about
      57 kidneys and 3 livers. That was why to introduce molecular biological methods
      of HLA-DR typing into the practical life of laboratory especially on duties
      seemed to be very advisable. We compare serological and PCR-SSP methods in group
      of 30 cadaveric donors in this article. The age median of our group was 36.5 yrs,
      the ratio men-women was 20:10.

PMID- 9916635
TI  - Experience with allogeneic and syngeneic blood stem cell transplantation in
      patients with hematological malignancies.
AB  - Between 1995 and 1997 twenty two patients with different hematological diseases (
      CML n=10, AML n=6, ALL n=l, NHL n=3, SAA n=1,solid tumor n=1 ) and a median age
      of 37 (range, 20 to 55) years received unmanipulated peripheral blood stem cell
      (PBSC) transplants from HLA-identical sibling donors at our institution.
      Myeloablative chemotherapy consisted of cyclophosphamide (CY) and total body
      irradiation in 11, and chemotherapy alone in 11 patients. For graft-versus host
      disease (GVHD) prophylaxis all patients were given cyclosporine A and
      methotrexate according to the Seattle protocol. PBSC were mobilized by
      granulocyte colony-stimulating factor (G-CSF) given at 10 microg/kg body weight
      (b.w.)/day for four days. Harvest of PBSC was started on day 5 and continued on
      day 6 if necessary. A median of 1 leukapheresis (range, 1 to 2) was performed and
      a median of 5.7 x 10(6) CD34+cells/kg b.w. (1.34 to 21.5) were obtained. Ten
      patients received G-CSF (5 microg/kg b.w.) starting on day one after PBSCT until
      neutrophil recovery. Absolute neutrophil counts >0.5 x 10(9)/L and ANC >1.0 x
      10(9)/L were reached after a median of 13 (range 8 to 18) and 15 (range 9 to 19)
      days after PBSCT. Unsupported platelet counts >20 x 10(9)/L and 50 x 10(9)/L were
      reached after 17 (range 8 to 32) and 22 (range 13 to 40) days after PBSCT,
      respectively. Incidence of acute GVHD grade I to IV was 52%, extensive chronic
      GVHD occurred in 25% of patients. After a median observation time of 11 (range, 3
      to 34) months twelve patients (55%) are alive and well. In summary, infusion of
      allogeneic PBSC after myeloablative therapy allows rapid and sustained
      hematologic reconstitution. Incidence of acute GVHD is not increased, for
      assessment of chronic GVHD longer observation times and larger patient numbers
      are required.

PMID- 9916636
TI  - Matched unrelated donor marrow transplantation in patients with advanced acute
      leukemia.
AB  - Patients with advanced acute leukemia (AL) have a poor prognosis with death due
      to disease or complications of therapy. High-dose chemoradiotherapy followed by
      allogeneic marrow transplantation (BMT) has been used to overcome resistance of
      the leukemic clone resulting in long-term survival of up to 20%. Due to lack of
      suitable related donors BMT from an HLA-compatible unrelated donor (MUD) has been
      increasingly applied in these patients during the last years. Between January
      1991 and August 1997 twenty five patients with advanced acute myeloid (n=19) or
      lymphoid (n=6) leukemia, 11 males and 14 females, age 22 to 41 (median 32) years
      received MUD (n=22) or 1-antigen mismatched unrelated donor (n=3) grafts. In four
      patients an autologous BMT had been performed previously. For conditioning all
      patients were given total body irradiation containing regimens. Graft-versus-host
      disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate
      (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region
      compatibility was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by
      hybridization of amplified DNA with ligation based typing. In 2 patients HLA-DR
      typing was performed by two colour fluorescence cytotoxicity test and mixed
      lymphocyte cultures. As of November 1997 10/25 patients (40%) are surviving
      leukemia-free after a median observation time of 17 (range, 3 to 38) months.
      Transplant-related mortality was an overall of 36% and 28% in patients receiving
      their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 months after
      BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse
      projected at 3 years was 35%. High-dose chemoradiotherapy followed by MUD marrow
      infusion has a curative potential for patients with advanced acute leukemia and
      offers the chance of long-term leukemia-free survival. Currently, up to 80% of
      patients with acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL)
      under the age of 50 years achieve complete hematological remission (CR) with
      conventional dose chemotherapy. However, in patients who are refractory to
      induction chemotherapy or relapse prognosis is still poor. There, high-dose
      chemoradiotherapy followed by allogeneic marrow infusion has been used to
      overcome resistance of the refractory leukemic clone and has resulted in long
      term survival. For selected patients lacking a human leukocyte antigen (HLA)
      compatible family donor marrow transplantation (BMT) with a suitable unrelated
      marrow donor (MUD) has become a feasible and effective treatment. Here, we report
      our experience in patients with advanced acute leukemia given marrow grafts from
      unrelated donors.

PMID- 9916637
TI  - Hematopoietic cell transplantation: activity and results of the BMT Unit K.Dluski
      Hosp./Inst.Immun. & Exp.Therapy, Wroclaw, Poland.

PMID- 9916639
TI  - Allogeneic bone marrow transplantation in children - eight years experience of
      Paediatric BMT Unit in Poznan.

PMID- 9916638
TI  - Haemopoietic cell transplantation activity and results: a single institution
      experience.
AB  - Between February 1993 and November 1997, 62 patients with severe aplastic anaemia
      (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia
      (CML) as well as two patients with NHL underwent allogeneic marrow
      transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or
      unrelated donors. Patients received preparative regimens according to the
      baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and
      TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two
      retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients
      conditioned traditionally with Bu/Cy. For GVHD prevention, patients received
      cyclosporin-A (CsA) with short course methotheraxe according to the Seattle
      protocol. Significantly better overall survival rates were associated with the
      Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole.
      Autologous stem cell transplantation (bone marrow and/or peripheral blood) were
      performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3
      Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with
      AML and two patients with NHL were conditioned with TBI/Cy and the others with
      BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma
      free survivors. One patient relapsed having conventional chemotherapy and
      interferon maintenance therapy. One patient died in a rapid relapse five months
      post-BMT.

PMID- 9916640
TI  - Allogeneic BMT for haematological disorders: single centre experience of
      University Hospital Bratislava.
AB  - Data on 65 sibling bone marrow transplantations (BMT) for various hematological
      disorders are reported. 51 patients had leukemia, 8 severe aplastic anemia, 4
      myelodysplastic syndrome, one suffered from non-Hodgkin lymphoma and one from
      myeloid metaplasia. All but two patients have engrafted. Overall, 43 (66%) of 65
      patients were alive 0,03-7,2 years (median not reached) as of June 23, 1997.
      Median time of observation was 13 months. Outcome of standard risk patients was
      significantly better than that of high risk patients (p=0,006). Our data confirm,
      that sibling BMT is an effective treatment modality with acceptable toxicity for
      younger patients with an early stage of serious hematological disorders.

PMID- 9916641
TI  - Allogeneic BMT for acute leukemia and chronic granulocytic leukemia in University
      Medical Centre Ljubljana-Slovenia.
AB  - Allogeneic BMT is treatment of choice for acute leukaemias(AL) and chronic
      granulocytic leukaemia (CGL). In the period form 1989 till 1997 36 allogeneic BMT
      have been performed for patients with AML, ALL and CGL using HLA matched related
      donors in University Medical Centre Ljubljana. The procedure was successful in
      80% of patients with CGL and in 50% of patients with AL. The most frequent cause
      of death in CGL patients was CMV pneumonitis, relapse in patients transplanted
      for ALL, while in patients transplanted for AML beside relapse we observed four
      deaths due to complications of BMT ( acute GVHD, VOD, thrombotic thrombocytopenic
      purpura, liver failure due to hepatitis).

PMID- 9916642
TI  - Transplantation of allogeneic peripheral blood progenitor cells--a single centre
      experience.
AB  - 13 patients have been transplanted at Institute of Hematology and Blood
      Transfusion since 1995 using allogeneic PBPC either alone or with bone marrow as
      a source of progenitor cells. All donors were G-CSF mobilised HLA identical
      family members. PBPC harvests were performed on D 4,5, (6) of G-CSF
      administration. The medium content of TNC, CD34+, CD3+, CD4+and CD8+cells/kg b.w.
      of the recipients in the grafts were: 13,1x10(8)(TNC), 11,4x10(6)(CD34+),
      393x10(6)(CD3+) 243x10(6)(CD4+), 125x10(6)(CD8+) The patients received either
      BuCy2 or CyTBI preparative regimen and Cyclosporin A + short course of
      Methotrexate for GVHD prophylaxis. Engraftment of ANC >500 was achieved by D+16
      and PLT >20.000 by D+19. Three of ten evaluable patients developed acute and
      three of nine chronic GVHD. 8 patients survive with the longest follow up 776
      days.

PMID- 9916643
TI  - Allogeneic bone marrow transplantation for acute leukemia in adults.
AB  - From September 1993 to August 1997, 24 consecutive adult acute leukemia patients
      (20 AML and 4 ALL) received allogeneic bone marrow transplant (21 sibling, 1
      twin, 2 MUD). The probability of 3 year leukemia free survival is 19/24 (79%),
      the transplant related mortality is 2/24 (8%), the relapse rate is 3/24 (13%).
      The median follow up period is 34 months (range 7-51). Three AML patients with
      high probability of TRM received a special radiation-free conditioning regimen
      (mitobronitol/cytarabine/ cyclophosphamide) originally described by Kelemen et al
      in CML patients for decreasing transplant related complications. All the three
      patients are alive and disease free over 3 years.

PMID- 9916644
TI  - Bone marrow transplantation in non-malignant disorders.
AB  - From January 1992 to December 1997, 21 consecutive patients (14 SAA, 3 SCID, 1
      Fanconi anemia, 1 Diamond-Blackfan anemia, 1 mucolipidosis and 1
      mucopolysaccharidosis type I.) were transplanted (16 HLA-id. family, 2 MUD and 3
      haploidentical family donors) in a single center. The median follow up period is
      41 months (range 7-76). The probability of 3.5 year overall disease free survival
      is 14/21 (67%), the transplant related mortality is 4/21 (19%). All the SCID
      patients are alive and disease free. 3 SAA patients had signs of fungal infection
      prior to transplant. They died in spite of intensive antifungal treatment
      resulting reduced DFS for SAA to 71%. Two patients with lysosomal storage
      disorders (mucolipidosis and MPS I.) rejected the haploidentical T-cell depleted
      graft 1 and 11 months after transplant, respectively. In 2 cases non-engraftment
      occured, both patients were retransplanted successfully.

PMID- 9916645
TI  - National Polish Blood/Marrow Transplant Registry-1984-1997.

PMID- 9916646
TI  - Long term follow up after allogeneic stem cell transplantation for chronic
      myelogenous leukemia.
AB  - Between January 1983 and July 1997, 83 patients (35 female, 48 male) with a
      median age of 37 (19-57) years with chronic myelogenous leukemia (CML) were
      admitted for bone marrow transplantation (BMT) at the University hospital of
      Vienna. Fifty-six patients were in chronic phase, 17 in accelerated and 10 had
      blast crisis. Marrow donors were: HLA-identical siblings in 62 patients, 2
      antigen mismatched related donor in 2, HLA-identical unrelated donors (MUD) in 17
      and 1-antigen mismatched unrelated donor in 2 patients. The median time from
      diagnosis to BMT was 22 (2-91) months. Conditioning therapy consisted of
      cyclophosphamide (CY) and total body irradiation or CY and busulfan. For graft
      versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone, MTX and
      cyclosporine A (CSA), CSA alone or CSA and methylprednisone were given. Durable
      engraftment was documented in 75 of 77 patients (97%). As of July 31, 1997 48
      patients are alive (58%), 36 (56%) after sibling transplantation with a median
      observation time of 77 months and 12 (63%) after MUD transplantation with a
      median observation time of 13 months. Overall survival for patients in chronic
      phase (CP) at time of BMT is 64%, 53% for patients in acceleration and 30% for
      patients in blast crisis (BC). Disease-free survival (DFS) after sibling BMT and
      unrelated donor transplantation is 53% and 58%, respectively. Ten patients (12%)
      experienced relapse of CML. Transplant-related mortality was 33% after sibling
      and 32% after MUD transplantation. Thus, sibling and unrelated donor BMT offer
      high cure rates with acceptable toxicity to patients with CML.

PMID- 9916647
TI  - Immunophenotypic characterisation of cord blood B-lymphocytes.
AB  - The phenotypic analysis of human umbilical cord blood (CB) mononuclear cells is
      important to study their maturity and differentiation regarding their
      transplantable capacity. In this work we have studied differential expression of
      B cell antigens on CD5-/HLA-DR+ B cells (B1b, B2) and CD5+/HLA-DR+ cells (Bla)
      from the CB (n=6) and adult peripheral blood (PB) (N=6). CD5-PE, HLA-DR-PerCP and
      FITC labelled anti-B cell MoAb panel of the 6th International Workshop on Human
      Differentiation Antigens were used for detection of B cell subpopulations.
      FacsCalibur (B-D) flow cytometer was used for evaluation of samples. CB Bla
      (CD5/HLA-DR++) cells proved to be positive with CD9, CD19, CD20, CD21, CD22,
      CD23, CD24, CD32, CD39, CD45RA, CD76, CD79, MHC-II, IgM and anti Ig light chains
      MoAbs. CB B1b (CD5-/HLA-DR+) cells reacted with CD9, CD19, CD20, CD21, CD22,
      CD23, CD24, CD32, CD39, CD45RA, CD79, MHC-II, and IgM MoAbs. PB B cells (B2)
      expressed CD19, CD20, CD21, CD22, CD24, CD32, CD37, CD39, MHC-II and CD79 Ags.
      Unlike to the PB the CB B lymphocytes proved to be predominantly B1 cells
      representing a new-born B cell repertoire. Besides expressing many B cell
      antigens both the CB Bla and B1b cells showed CD9+, CD45RA+, IgM+ immature,
      "naive" B cell phenotype. Functionally, B1 cells are capable producing
      polyreactive IgM and natural autoantibodies but not IgG. This antibody profile
      might be insufficient regarding the recipient humoral immune defense result in
      more severe immunodeficiency after CB transplantation.

PMID- 9916648
TI  - The number of particular hematopoietic progenitors cells and the haematopoietic
      recovery following Allo PBSCT.
AB  - AlloPBSC-T is rapidly replacing bone marrow transplantation. The minimum number
      of progenitor cells required for rapid engraftment following PBSCT is unknown. 12
      patients underwent alloPBSC-T during treatment for haematological malignancy.
      PBSC's were mobilised with Filgrastim (10microg/kg/day sc). The mobilisation was
      monitored daily by the number of mononuclear cells (MNC) and CD34+ cells in
      peripheral blood. Collections were normally performed on days 4 and 5, by means
      of apheresis (Fenwall CS 3000+). No further manipulation of PBSC was performed. A
      median of 10.15x10(8)/kg MNC (range 5.87-12.24), 9.075x10(6)/kg CD34+ (range 0.78
      18.98), 53.85x10(4)/kg CFU-G (range 17.2-138.4), 28.05x10(4)/kg CFU-M (range 4.1
      102.2), 115.65x10(4)/kg BFU-E (range 9.1-255.2), 3.65x10(4)/kg CFU-GEMM (range
      0.3-10.4) were infused into recipients following BuCyl20 conditioning.
      Haematopoietic reconstitution was observed in 11 patients. The median number of
      days to achieve a neutrophil count of 0.5x10(9)/l was 16 (range 12-20), the
      platelet count of 20x10(9)/l was 12 (range 8-20) and RBC transfusion independence
      was 11 (range 8-20). 9 recipients developed acute GVHD (3 grade I0, 2 grade II0,
      1 grade III0, 3 grade IV0). We found that the number of MNC in PBSC had no
      influence on the number of progenitors. All the patients who received G
      CFU>20x10(4)/kg, BFU-E>60x10(4)/kg and CFU-GEMM>1x10(4)/kg experienced a rapid
      haematopoietic recovery. No relation was found between the number of reinfused
      progenitors and the appearance of GVHD.

PMID- 9916649
TI  - Early post-BMT liver function in children with acute leukemia conditioned for
      allo-BMT with Busulfan-containing and with FTBI-containing preparative regimens.

PMID- 9916650
TI  - Allogeneic and autologous bone marrow transplantation in single centre
      experience.
AB  - Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11
      MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in
      76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were
      calculated using the Kaplan-Meier product limit method. Variables potentially
      affecting survival and DFS were assessed in a multivariate analysis by the Cox
      proportional hazard model in a stepwise regression. The promising results were
      obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted
      after full dose induction and high dose consolidation was significantly longer if
      compared to those who received dose/time reduced or postponed treatment. For CR>
      or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage
      therapy that needs further improvement. In relapsed and refractory HD better
      results are obtained in patients relapsing > 1 year after first CR and in
      patients with entirely nodal localisation of this relapse. In NHL bone marrow and
      spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.

PMID- 9916651
TI  - Autologous stem cell transplantation for malignant lymphomas.
AB  - From December 1995 to April 1998, 20 consecutive adult patients suffering from
      chemosensitive relapse of Hodgkin's or non-Hodgkin lymphoma (11 Hodgkin, 9 non
      Hodgkin Lymphoma) received autologous stem cell transplantation. The median
      follow up period is 15 months (range 6-28). The overall survival is 18/20 (90 %),
      the event free survival is 13/20 (65%). None of the patients died of transplant
      related cause.

PMID- 9916652
TI  - High-dose chemotherapy with autologous hematopoietic progenitor cell
      transplantation in children with high-risk NHL and ALL-preliminary results.
AB  - Since May 95 to December 97 twenty children with NHL (n=14, NHL B = 11, NHL NB =
      3) or ALL (n=6, high risk n=2, standard risk n=4) underwent high-dose
      chemotherapy with subsequent autologous hematopoietic progenitor cells
      transplantation. In 19 children progenitor cells were harvested with the use of
      Fenwal CS3000 Plus cell separator from the peripheral blood after cytotoxic
      mobilization with G-CSF (Neupogen 5 microg/kg). One patient received PBPC and
      autologous bone marrow. One patient received positively selected CD34+ cells
      (CeprateSC, CellPro). One patient received autologous marrow purged with
      mafosfamide. All patients with NHL received conditioning according to BEAM
      protocol. Patients with ALL were conditioned with BU,CY,VP, BU,CY or BU. The
      median number of transplanted CD34+ cells was 3.84x10(6) (0.51x10(6)-74.7x10(6)).
      Children transplanted with unmanipulated hematopoietic progenitor cells recovered
      in granulocytes >500/microl at a median time of 12 days (range from 9 to 28
      days). Platelet recovery >50000/microl was observed at a median time of 26 days
      (range from 13 to 347days). Sixteen children (80 %) are alive and well in
      continuous complete remission from 4 to 36 months after transplantation (median
      +20). Three children (15%) relapsed and died because of the disease. One patient
      died in complete remission on day +41 because of aspergillosis. Transplant
      related mortality was 5,0%. Overall survival was 79%. Event free survival was 86%
      in NHL and 67% in ALL.

PMID- 9916653
TI  - Current activity and perspectives of Clinical and Transplantation Immunology
      Division, Medical University, Sofia, Bulgaria.
AB  - Our unit was established in 1972 as Laboratory of Clinical Immunology in the
      Department of Nephrology, Medical Academy, Sofia Since 1985 it was expanded in
      Division of Clinical and Transplantation Immunology. Transplantation activity
      includes: HLA typing (serology and DNA) of all kind of recipients and donors,
      alloantibody screening and crossmatching (basic microlymphocytotoxicity, DTT and
      flowcytometry tests). Immunologic evaluation of patients prior to and after
      transplantation is also performed for individualization of immunosuppressive
      therapy and discrimination between rejection, CMV infection and cyclosporine
      toxicity. Since 1983 till now 1662 candidates for kidney transplantation were
      immunologically tested and registered in Bulgaria. During the same period 293
      donors (109 cadaveric and 184 living related) were also typed. The number of
      transplanted patients from the waiting list is 221. 123 transplantations (76 from
      cadaveric and 52 from living related donors) were performed in our country and
      the rest abroad. Because of the imbalance in numbers between cadaveric and living
      related donors and recipients, the waiting time for transplant candidates has
      increased, and tragically, the high percentage of patients are dying or become
      unsuitable while awaiting transplantation. In the field of bone marrow
      transplantation our laboratory performs the tissue typing of patients and all
      available members of the immediate family in order to search for histocompatible
      sibling donor. As recipient numbers continue to grow, both in absolute terms and
      relative to the number of available donor organs, our histocompatibility
      laboratory attempts to provide the best possible immune testing to ensure an
      optimal transplant outcome.

PMID- 9916654
TI  - Flow cytometry cross-match before kidney transplantation in relation to early
      postransplant rejection.
AB  - The aim of this study was to compare flow cytometry cross match (FCXM) results in
      patients before first kidney transplantation with the incidence of rejection
      episodes and kidney graft survival after transplantation. Sera of 51 patients
      obtained immediately before transplantation were tested on spleen cells of
      respective kidney donors. We found no correlation between a positive FCXM result
      before transplantation and the occurrence of immunological complications after
      transplantation.

PMID- 9916655
TI  - Tissue banking 1997; standardization of procedures.

PMID- 9916656
TI  - Educational programme of Slovak Foundation: Education in Immunogenetics and its
      collaboration with the NATO. North Atlantic Treaty Organization.

PMID- 9916657
TI  - Pancreatic enzymes: secretion and luminal nutrient digestion in health and
      disease.
AB  - Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is
      one of the most important late features of chronic pancreatitis. In contrast to
      other key enzymes, pancreatic synthesis and secretion of lipase is impaired more
      rapidly, its intraluminal survival is shorter due to its higher susceptibility
      against acidic and proteolytic denaturation, and its luminal digestive action is
      hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is
      in general more severe and occurs several years before clinical malabsorption of
      protein or starch. Apart from the detrimental effects of nutrient deficiency,
      profound alterations of upper gastrointestinal secretory and motor functions may
      be an additional and hitherto underestimated consequence of increased nutrient
      delivery to distal intestinal sites. Effective reduction of nutrient
      malabsorption in pancreatic insufficiency requires delivery of sufficient
      enzymatic activity into the duodenal lumen simultaneously with meal nutrients.
      Modern enteric-coated pancreatin microsphere preparations attempt to achieve this
      by optimizing the size of individual microspheres and chemical properties of the
      coating. However, lipid digestion cannot be completely normalized in most
      patients by current standard therapy. In the future, acid and protease stable
      bacterial and fungal lipases with additional pH optima in the acidic milieu or
      animal or bioengineered human gastric lipase preparations may offer superior
      therapeutic alternatives. This review first summarizes current knowledge about
      secretion and luminal fate of pancreatic enzymes and their effects on nutrient
      digestion in health and chronic pancreatitis. Second, rationale, current
      standards, options, and future aspects of enzyme replacement therapy are
      discussed.

PMID- 9916658
TI  - Clinical pharmacology and use of laxatives and lavage solutions.
AB  - Laxatives and lavage solutions are used in the treatment of constipation and
      toxic ingestion and also for preparation of the colon before endoscopic or
      surgical procedures. Several different categories of agents are available for
      use. These include bulking agents, osmotic agents, secretagogues and agents with
      direct effects on epithelial nerve or smooth muscle cells, and lubricating
      agents. Each category has different pharmacologic effects, side effects, and
      clinical indications. This review summarizes current information about these
      agents.

PMID- 9916659
TI  - The small polyp at flexible sigmoidoscopy: an historical perspective on why
      practices still vary.
AB  - Current practices vary regarding the approach to small polyps discovered during
      screening flexible sigmoidoscopy. The most common practice is to perform
      colonoscopy whenever any adenoma is detected, a strategy that generally uses
      biopsy of polyps < or = 5 mm in size. However, data suggest that tubular adenomas
      < 1 cm in size in the distal colon have less predictive value than other distal
      adenomas for advanced adenomas in the proximal colon. Thus, some centers reserve
      colonoscopy for distal adenomas with tubulovillous or villous histology, > 1 cm
      in size, or with high-grade dysplasia. At the other end of the spectrum, another
      school of thought advocates screening colonoscopy, recognizing that most patients
      with advanced proximal adenomas do not have polyps in their distal colon.
      Advocates of this approach use any excuse to perform colonoscopy, whether it be a
      positive fecal occult blood test, minor symptoms, or small polyp at flexible
      sigmoidoscopy, even if hyperplastic. This review describes the history of the
      controversy regarding management of findings at flexible sigmoidoscopy, the data
      pertinent to the controversy, and the basis for the three approaches described
      above, all of which are currently within the standard of medical care.

PMID- 9916660
TI  - Hepatitis C virus seroconversion and genotype prevalence in patients and staff on
      chronic hemodialysis.
AB  - The prevalence of hepatitis C virus (HCV)-RNA positivity among hemodialysis
      patients varies between 10 and 70%. Few previous surveys revealed high frequency
      of seroconversion of HCV-RNA-negative patients over the years of hemodialysis.
      Only few studies reported HCV genotype variability. We evaluated all 65 patients
      on chronic hemodialysis in our dialysis unit. All sera positive to anti-HCV on
      ELISA were retested by reverse transcriptase polymerase chain reaction to HCV
      RNA. Sixteen patients were found anti-HCV positive on ELISA, and 8 of them were
      also PCR positive. Three of these eight patients seroconverted during the year
      1995. Four patients had both 1a and 1b genotypes of HCV, coexistence of genotypes
      1b and 4a in one patient and genotypes 1a, 1b and 2a in the remaining three
      patients. Mean serum aminotransferase, duration of dialysis, and number of blood
      units transfused were significantly higher in the HCV-PCR-positive patients
      compared with the HCV-PCR-negative patients. Because strict isolation methods
      were initiated at the end of 1995, not one new case of HCV among dialysis
      patients was found in 1998, although new hemodialysis patients were diagnosed as
      having HCV. In conclusion, genotypes 1a and 1b, as is true for the general
      population in Israel, were also the predominant genotypes among hemodialysis
      patients; the coexistence of more than one genotype is common among hemodialysis
      patients; seroconversion is common among these patients and strict isolation
      methods are efficient and should be recommended.

PMID- 9916661
TI  - Effect of increased fluid intake on stool output in normal healthy volunteers.
AB  - Constipation is a common condition affecting millions of people throughout the
      world. The present study aimed to determine the effect of extra fluid intake, as
      recommended by many primary care physicians and gastroenterologists, on the
      actual stool output in normal healthy volunteers. We recruited 15 healthy
      volunteers (aged 23-46 years, mean 30.1) without any significant history of
      diarrhea or constipation to participate in our study. Nine subjects underwent
      extra intake of isotonic fluids (Gatorade), whereas the remainder received extra
      free water over their baseline. During period I (3 days), baseline diet and fluid
      intake were determined by a registered dietitian. During periods II and III (2
      days each), the volunteers in each group increased their fluid intake by 1 and 2
      l of isotonic (Gatorade) and hypotonic solution (water), respectively. Period IV
      (2 days) completed the study with the volunteers returning to their baseline
      fluid intake. Urine and stool outputs were measured in these volunteers.
      Additional increase in fluid intake (isotonic or free water) did not result in a
      significant change in stool output. However, there was a significant increase in
      urine output (P < 0.05). Despite common medical advice to consume extra fluid for
      constipation, our results indicate that extra fluid intake in normal healthy
      volunteers did not produce a significant increase in stool output.

PMID- 9916662
TI  - Endoscopic balloon dilatation of peptic pyloroduodenal strictures.
AB  - A through-the-scope endoscopic balloon dilatation technique and acid-reducing
      medication was used in 46 consecutive patients (median age, 55; range, 21-88
      years) with benign gastric outlet obstruction. In five patients, dilatation was
      not technically possible. In 41 patients, 122 dilatations (median, 2; range, 1-9
      per patient) were performed without morbidity. Ninety-four procedures were
      successful (77%) at the initial attempt (able to pass a 12-mm endoscope into the
      duodenum at the end of the procedure). Median follow-up in the 41 patients was 19
      (range, 1-78) months. Thirteen patients (32%) required subsequent surgery; 8 had
      delayed operation for persistent symptoms (1-28 months after the first
      dilatation), 1 had surgery during the initial hospital admission, and 4 required
      emergency surgery for other ulcer complications (3 perforation, 1 bleeding). Of
      the 28 patients who had only balloon dilatation and medical therapy, 11 are
      asymptomatic (4 with active ulceration), 9 have mild symptoms (Visick 2), and 3
      have persistent symptoms (Visick 3). One patient was lost to follow-up and four
      patients have died (one from an ulcer-related complication). Balloon dilatation
      and sustained acid-reducing therapy with regular endoscopic surveillance should
      be first-line treatment of peptic pyloroduodenal strictures, because the
      procedure is safe and is likely to be successful in half of the patients in whom
      dilatation is technically possible.

PMID- 9916663
TI  - Correlation of ambulatory 24-hour esophageal pH monitoring results with symptom
      improvement in patients with noncardiac chest pain due to gastroesophageal reflux
      disease.
AB  - Gastroesophageal reflux disease (GERD) accounts for up to 60% of patients with
      noncardiac chest pain (NCCP). Twenty-four-hour esophageal pH monitoring has been
      considered the most sensitive test for identifying acid reflux as the probable
      cause for chest pain. It is unclear if there is a correlation between the degree
      of esophageal acid exposure as determined by 24-hour esophageal pH monitoring and
      symptom improvement during a short course of high-dose omeprazole (the omeprazole
      test) in patients with NCCP due to GERD. Twenty-three patients with GERD-related
      NCCP were studied. All patients were referred by a cardiologist and evaluated by
      upper endoscopy and 24-hour esophageal pH monitoring. Diagnosis of GERD was
      defined by one or both tests being abnormal. Subsequently, patients underwent
      baseline symptom intensity assessment during 1 week off therapy followed by 1
      week on therapy with high-dose omeprazole (40 mg A.M. and 20 mg P.M.). There was
      a statistically significant correlation between the esophageal acid exposure by
      24-hour esophageal pH monitoring and the change in symptom intensity score after
      treatment. However, there was no significant correlation between the pH values
      and symptom intensity score during baseline or during the omeprazole test. In
      patients with GERD-related NCCP undergoing the omeprazole test, 24-hour
      esophageal pH monitoring has a therapeutic predictive value in addition to its
      diagnostic merit. Patients with greater esophageal acid exposure appear to have a
      greater response to antireflux treatment.

PMID- 9916664
TI  - Sucralfate in the prevention of radiation-induced oral mucositis.
AB  - Radiotherapy-induced mucositis decreases the quality of life by impairing eating,
      swallowing, and talking and by disturbing sleep. Mucositis may also predispose to
      local and systemic infections and may cause interruption of radiotherapy course.
      We studied the efficacy of sucralfate suspension in the prevention and management
      of oral mucositis and pain during radiotherapy in a double-blind, placebo
      controlled, randomized, prospective trial. Twenty-eight patients with head and
      neck cancer were included in the study. The patients were randomized to use
      either sucralfate mouth washing (n = 18) or placebo washing (n = 10) during
      irradiation. Oral mucositis and symptoms were assessed by the same physician
      using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring
      criteria. All patients developed varying degrees of radiation-induced mucositis.
      Grade 4 mucositis was not encountered in any patient. One patient had grade 1,
      seven patients grade 2, and two patients grade 3 mucositis in placebo group. In
      sucralfate group, nine patients each had grade 1 and grade 2 with no grade 3
      mucositis. Patients in the sucralfate group experienced significantly lower
      degree of mucositis than placebo group (p < 0.05). Sucralfate mouth washing is
      beneficial in decreasing the intensity of radiation-induced mucositis and oral
      discomfort. It is cheap, easy to administer with no serious side effect, and may
      be routinely used in patients receiving head and neck radiotherapy.

PMID- 9916665
TI  - Granulomatous hepatitis due to mebendazole.

PMID- 9916666
TI  - Spontaneous bacterial peritonitis caused by Streptococcus gordonii.

PMID- 9916667
TI  - Isolated transverse mesocolon laceration during routine colonoscopy.

PMID- 9916668
TI  - Complete response to twice-a-day interferon-beta with standard interferon-alpha
      therapy in acute hepatitis C after a needle-stick.
AB  - A 25-year-old male physician with acute hepatitis C after needle-stick injury was
      treated with combination therapy including twice-a-day interferon-beta (IFN-beta)
      and standard interferon-alpha (IFN-alpha). The infecting strain was of genotype
      1b. Pretreatment hepatitis C virus (HCV) RNA levels were high. Because severe
      paresthesias occurred with initial daily administration of 5 million units (MU)
      of lymphoblastoid IFN-alpha, the dose was reduced to 3 to 6 MU of IFN-alpha2b
      three times a week. However, HCV RNA was not cleared from serum after 20 weeks of
      standard IFN-alpha2b treatment. A 4-week course with IFN-beta, at the dosage of 3
      MU twice daily i.v. drip, was then started and followed by an 18-week course with
      IFN-alpha2b, 6 MU thrice weekly. After IFN-beta treatment, HCV RNA was cleared
      from serum without severe adverse effects, including paresthesias. Total amounts
      of IFN administered were 20 MU of lymphoblastoid IFN-alpha, 648 MU of IFN
      alpha2b, and 252 MU of IFN-beta. Complete response and avoidance of chronic HCV
      infection were achieved. Thus, combination therapy with twice-a-day IFN-beta and
      standard IFN-alpha was effective in treating an acute hepatitis C patient with a
      high viral load and sensitivity to adverse effects of high-dose IFN-alpha.

PMID- 9916669
TI  - Atrium and paroxetine-related severe hepatitis.
AB  - Two cases of severe hepatitis in young women using Atrium and paroxetine are
      presented. Both patients presented jaundice, marked increase in aminotransferases
      activities, and pronounced prolongation in prothrombin time. In both cases, liver
      biopsy specimen examination revealed lesions compatible with drug-related injury.
      Other causes of hepatic injury were reasonably ruled out by complete careful
      screening. Outcome was marked by rapid complete recovery in one case and by slow
      recovery in the other. We suggest that simultaneous treatment with Atrium and
      paroxetine could increase each of these drugs' hepatotoxicity.

PMID- 9916670
TI  - Biliary tract obstruction secondary to mycosis fungoides: a case report.
AB  - Mycosis fungoides is a cutaneous T-cell lymphoma that can disseminate to multiple
      organs. We report a patient who presented with obstructive jaundice caused by
      isolated involvement of the extrahepatic biliary tree by mycosis fungoides.
      Initially, endoscopic examinations and biopsies of the biliary tree and liver
      failed to reveal a cause for the obstructive symptoms. Finally, surgical
      resection of the gallbladder and extrahepatic ducts was performed. Examination
      revealed a dense, mixed lymphocytic infiltrate with atypical cells within the
      mucosa. Gene rearrangement studies confirmed the presence of a monoclonal T-cell
      population. The pattern of the gene rearrangement in the biliary tree was
      identical to that found in a previous skin biopsy that showed mycosis fungoides.
      Although liver involvement by mycosis fungoides is not uncommon, disease isolated
      to the extrahepatic biliary tree has not previously been reported. This case
      should alert clinicians and pathologists to yet another cause of obstructive
      jaundice.

PMID- 9916671
TI  - Hepatic sarcoidosis and renal carcinoma.
AB  - Sarcoidosis is a relatively common, chronic, multisystem disease of unknown
      origin. It most commonly affects young adults and usually manifests with
      bilateral hilar lymphadenopathy or pulmonary infiltrates. Alternatively, it may
      present with protean manifestations. It has been documented in all organs of the
      body, with the exception of the adrenal gland. We describe a male patient who
      presented with hepatic sarcoidosis, with a sclerosing cholangitis-like picture,
      but without any pulmonary involvement. He was treated with prednisolone and
      cyclophosphamide, the latter as a steroid-sparing agent. A few years later, renal
      adenocarcinoma developed. We postulate that this could be related to
      cyclophosphamide treatment. We present this case history for two reasons: (1)
      sarcoidosis, selectively affecting the liver and lymph nodes but not the lung,
      with its hepatic involvement mimicking sclerosing cholangitis, has not previously
      been reported: and (2) although long-term cyclophosphamide treatment is known to
      be associated with malignancy, there is only one previous report of its
      association with a renal adenocarcinoma.

PMID- 9916673
TI  - Early carcinoma of the distal second part of the duodenum treated by wedge
      resection.
AB  - A case of early carcinoma of the distal second part of the duodenum, in a 74-year
      old man, is presented. Endoscopic retrograde cholangiopancreatography was
      performed for diagnosis of a common bile duct stone. During this procedure, small
      elevated lesions were found incidentally in the distal second part of the
      duodenum, and the histologic examination of a biopsy specimen showed
      adenocarcinoma. The lesions were removed by wedge resection, and pathologic
      examination revealed duodenal carcinoma limited to the lamina propria. Although
      carcinoma of the duodenum, other than of the ampulla of Vater region, is very
      rare, it is sometimes possible to detect asymptomatic early tumors. However, this
      requires careful observation of the entire duodenal mucosa, including that of the
      distal duodenum, at duodenoscopy.

PMID- 9916672
TI  - Long-term survival of a young woman with peripheral cholangiocarcinoma: a case
      report.
AB  - Cholangiocarcinoma is the second most common primary tumor of the liver after
      hepatocellular carcinoma and accounts for 5 to 25% of primary hepatic
      malignancies. Patients with intrahepatic or peripheral cholangiocarcinoma (ICC)
      most often present at an advanced stage leading to a poor prognosis. A review of
      the literature has produced only 10 patients who have survived over five years.
      We review the case of a young woman with a large cholangiocarcinoma, who has been
      disease free for eight years. The patient was treated with a right hepatic
      lobectomy, and received 4 cycles of 5-fluorouracil and levamisole
      postoperatively. Known factors associated with longer survival in patients with
      ICC include lack of evidence of local invasion (i.e. capsular, lymphatic, or
      vascular), negative margins, mucoblia, and well differentiation of the tumor, as
      well as the absence of lymph node metastases. Our patient had negative margins
      and lymph nodes, and showed no local invasion. However, no mucobilia was noted,
      and the tumor was only moderately differentiated. Young age has never been
      associated with increased survival. ICC remains a relatively uncommon tumor with
      an insidious onset and late presentation contributing to poor survival. Surgical
      resection remains the only therapeutic option. Since few patients are potentially
      resectable at the time of presentation, efforts at early diagnosis and options
      for adjuvant therapy are imperative.

PMID- 9916674
TI  - Acute pancreatitis in adult type IV congenital cyst of bile ducts: report of two
      cases.
AB  - Type IV congenital cyst of bile duct represents about 10% of all bile duct
      congenital cysts in adulthood. Clinical presentation is usually related to
      recurrent jaundice and abdominal pain. No cases of type IV bile duct cyst
      presenting with acute pancreatitis have been described so far. We herein report
      two cases of such association; both patients recovered from acute pancreatitis.
      The relevant world literature is reviewed.

PMID- 9916675
TI  - Pancreatitis in ulcerative colitis: a case report of improved stricture of the
      main pancreatic duct.
AB  - We present one case with pancreatitis that synchronized with manifestations of
      ulcerative colitis, in which an improvement of stricture of the main pancreatic
      duct was observed. A 27-year-old man, having a history of nonalcoholic acute
      pancreatitis, complained of anal bleeding and pain in the epigastric region. The
      treatment for pancreatitis relieved the pain and decreased the serum levels of
      pancreatic enzymes to within normal ranges. Colonoscopy and histopathologic
      examination revealed ulcerative colitis in the rectum, and treatment with steroid
      enema made proctitis quiescent. Endoscopic retrograde pancreatography
      demonstrated a remarkable and short stricture of the main pancreatic duct, which
      improved at follow-up pancreatography. In a 20-month follow-up period, active
      proctitis relapsed with a episode of recurrent pancreatitis once, and without
      pancreatitis once.

PMID- 9916676
TI  - Strongyloidiasis colitis: a case report and review of the literature.
AB  - A case is described of a nonimmunocompromised man who presented with diarrhea,
      weight loss, and microcytic anemia. Colonoscopy revealed a pancolitis
      characterized by aphthoid ulceration on endoscopy and intense tissue eosinophilic
      infiltrates on biopsy. Both colonic biopsies and stool aspirates revealed the
      larvae of Strongyloides stercoralis, thus confirming this parasite as the
      causative agent for the colitis.

PMID- 9916677
TI  - Morgagni hernia: unique presentations in elderly patients.
AB  - We present case reports of 2 patients who were admitted to our ward for
      complications of Morgagni hernias. Both patients were elderly. Morgagni hernia is
      a rare condition. Its unique and late presentation are presented and discussed.

PMID- 9916678
TI  - Duodenal stenosis and Helicobacter pylori.

PMID- 9916679
TI  - Cutting edge: protective effects of notch-1 on TCR-induced apoptosis.
AB  - The Notch receptor protein was originally identified in Drosophila and is known
      to mediate cell to cell communication and influence cell fate decisions. Members
      of this family have been isolated from invertebrates as well as vertebrates. We
      isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77, which is a
      protein that has been shown previously to be required for apoptosis in T cell
      lines. The data presented below indicate that Notch-1 expression provides
      significant protection to T cell lines from TCR-mediated apoptosis. These data
      demonstrate a new antiapoptotic role for Notch-1, providing evidence that, in
      addition to regulating cell fate decisions, Notch-1 can play a critical role in
      controlling levels of cell death in T cells.

PMID- 9916680
TI  - Cutting edge: induction of enhanced CTL-dependent protective immunity in vivo by
      N-end rule targeting of a model tumor antigen.
AB  - There is much interest in vaccines that will enhance the induction of CTL. One
      mechanism to enhance Ag-specific CTL responses involves targeting Ag to undergo
      rapid cytoplasmic degradation by the N-end rule pathway. We have analyzed the
      ability of N-end rule targeting to confer protection in an immunization-challenge
      setting. Using the HIV-1 nef protein as a model tumor Ag, we found that in mice
      immunized with a vaccinia vector expressing a form of nef that is targeted for
      rapid cytoplasmic degradation, there was enhanced induction of nef-specific CTL
      and protection from a lethal challenge with the syngeneic CT26 tumor cells that
      had been transfected with nef. Protection from tumor challenge correlated with
      the magnitude of the CTL response. Thus, the targeting of tumor or viral Ags for
      rapid cytoplasmic degradation by the N-end rule pathway may represent a strategy
      for the induction of protective Ag-specific CTL responses in vivo.

PMID- 9916681
TI  - The role of the antigen-presenting cell in Fas-mediated direct and bystander
      killing: potential in vivo function of Fas in experimental allergic
      encephalomyelitis.
AB  - Costimulatory molecules are critical in mediating Fas-dependent direct and
      bystander lysis. In direct lysis, the APC is the Fas-positive target. It presents
      Ag to the T cell, thereby activating the T cell. The activated T cell then up
      regulates FasL, allowing it to kill the APC. In bystander lysis, the APC again
      induces FasL expression on the T cell, but the target is a third Fas-positive
      cell that may lack the appropriate MHC-restricting element to activate the T
      cell. This study shows that ICAM-1 and B7-1 can serve as important adhesion
      molecules in direct killing using CD4+ T cell effectors. In bystander killing, B7
      1 appears to act as a signaling molecule as well. It has been demonstrated that
      lpr and gld mice are less susceptible to experimental allergic encephalomyelitis
      than their wild-type counterparts. In this study, we show that although microglia
      are poor targets of direct killing, they are capable of stimulating myelin basic
      protein-specific T cells to kill innocent Fas-positive targets. This presents a
      possible mechanism for the pathogenesis of experimental allergic
      encephalomyelitis.

PMID- 9916682
TI  - CTLA-4 (CD152) inhibits the specific lysis mediated by human cytolytic T
      lymphocytes in a clonally distributed fashion.
AB  - Since the functional outcome of effector T lymphocytes depends on a balance
      between activatory and inhibitory receptors, we studied the ability of CTLA-4
      (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+
      CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was
      inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones
      inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%.
      This suggests the existence of a clonal heterogeneity as well as for the ability
      of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support
      further this contention, we used an experimental model based upon Ag-specific
      CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B
      lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were
      used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor
      (i.e., CTLA-4 Ig) were included. In this system, at variance from the redirected
      killing assay, cross-linking of surface molecules by mAb does not occur. Thus,
      addition of anti-CD152 mAb or of CTLA-4 Ig and anti-CD80/CD86 mAb to the assay
      should result in a blockade of receptor/ligand interactions. As a consequence,
      inhibition of a negative signal, such as that delivered via CD152, should enhance
      lysis. A >40% increment of target cell lysis was achieved in three of eight
      clones studied. Since it is not equally shared by all CTL clones, this feature
      also appears to be clonally distributed.

PMID- 9916683
TI  - T cell activation signals up-regulate p38 mitogen-activated protein kinase
      activity and induce TNF-alpha production in a manner distinct from LPS activation
      of monocytes.
AB  - p38 mitogen-activated protein kinase (MAPK) (p38) is involved in various cellular
      responses, including LPS stimulation of monocytes, resulting in production of
      proinflammatory cytokines such as TNF-alpha. However, the function of p38 during
      antigenic stimulation of T cells is largely unknown. Stimulation of the human Th
      cell clone HA-1.70 with either the superantigen staphylococcal enterotoxin B
      (SEB) or with a specific antigenic peptide resulted in p38 activation and the
      release of TNF-alpha. MAPK-activated protein kinase-2 (MAPKAPK-2), an in vivo
      substrate for p38, was also activated by T cell signaling. SB 203580, a selective
      inhibitor of p38, blocked p38 and MAPKAPK-2 activation in the T cell clone but
      did not completely inhibit TNF-alpha release. PD 098059, a selective inhibitor of
      MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase
      (ERK) and partially blocked TNF-alpha production by the clone. In human
      peripheral T cells, p38 was not activated by SEB, but rather by CD28 cross
      linking, whereas in the human leukemic T cell line Jurkat, p38 was activated by
      CD3 and CD28 cross-linking in an additive fashion. TNF-alpha production by
      peripheral T cells in response to SEB and anti-CD28 mAb correlated more closely
      with ERK activity than with p38 activity. Therefore, various forms of T cell
      stimulation can activate the p38 pathway depending on the cells examined.
      Furthermore, unlike LPS-stimulated monocytes, TNF-alpha production by T cells is
      only partially p38-dependent.

PMID- 9916684
TI  - Hepatitis C virus envelope glycoprotein E1 originates in the endoplasmic
      reticulum and requires cytoplasmic processing for presentation by class I MHC
      molecules.
AB  - We investigated whether hepatitis C virus envelope glycoprotein E1 is transported
      from the endoplasmic reticulum (ER) to the cytoplasm of infected cells for class
      I MHC processing. Target cells expressing E1 were killed by CTL lines from a
      hepatitis C virus-infected chimpanzee, and synthetic peptides were used to define
      an epitope (amino acids 233-GNASRCWVA-241) presented by the Patr-B*1601 class I
      MHC molecule. An unusually high concentration (>100 nM) of this nonameric peptide
      was required for target cell lysis, but this could be reduced at least 1000-fold
      by replacing the asparagine at amino acid position 234 (Asn234) with aspartic
      acid (Asp), the anticipated anchor residue for NH2-terminal peptide binding to
      Patr-B*1601. Conspicuously, position 234 is part of an N-glycosylation motif (Asn
      Xaa-Ser/Thr), suggesting that the Asn234 to Asp substitution might occur
      naturally within the cell due to deglycosylation/deamidation of this amino acid
      by the cytosolic enzyme peptide N-glycanase. In support of this model, we
      demonstrate that presentation of the epitope depended on 1) cotranslational
      synthesis of E1 in the ER, 2) glycosylation of the E1 molecule, and 3) a
      functional TAP transporter to shuttle peptide from the cytosolic to ER
      compartment. These results indicate for the first time that during infection of
      the host, viral envelope glycoproteins originating in the ER are processed in the
      cytoplasm for class I MHC presentation. That a posttranslational change in amino
      acid sequence from Asn to Asp alters the repertoire of peptides presented to CD8+
      CTL has implications for the design of antiviral vaccines.

PMID- 9916686
TI  - Inhibition of Th1 polarization by soluble TNF receptor is dependent on antigen
      presenting cell-derived IL-12.
AB  - Th1-polarized CD4+ T cells are considered central to the development of a number
      of target-directed autoimmune disorders including multiple sclerosis. The APC
      derived cytokine IL-12 is a potent inducer of Th1 polarization in T cells.
      Inhibition of IL-12 in vivo blocks the development of experimental allergic
      encephalomyelitis, the animal model for multiple sclerosis. Based on previous
      work that suggests that the production of IL-12 by activated human central
      nervous system-derived microglia is regulated by autocrine TNF-alpha, we wanted
      to determine whether inhibition of TNF could induce a reduction of Th1 responses
      by its impact on systemic APCs. We found that soluble TNFR p75-IgG fusion protein
      (TNFR:Fc) inhibited production of IFN-gamma by allo-Ag-activated blood-derived
      human CD4 T cells. We documented reduced IL-12 p70 production by APCs in the MLR.
      By adding back recombinant IL-12, we could rescue IFN-gamma production,
      indicating that TNFR:Fc acts on APC-derived IL-12. Consistent with an inhibition
      of the Th1 polarization, we found a decreased expression of IL-12R-beta2 subunit
      on the T cells. Furthermore, the capacity of T cells to secrete IFN-gamma upon
      restimulation when previously treated with TNFR:Fc is impaired, whereas IL-2
      secretion was not altered. Our results define a TNF-dependent cytokine network
      that favors development of Th1 immune responses.

PMID- 9916685
TI  - Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B
      cells in vitro and signals via a novel mechanism.
AB  - A novel cytokine from a thymic stromal cell line (thymic stromal lymphopoietin
      (TSLP)) promotes the development of B220+/IgM+ immature B cells when added to
      fetal liver cultures, long term bone marrow cultures, or bone marrow cells plated
      in semisolid medium. Because the activities of TSLP overlap with those of IL-7 in
      some in vitro assays, we compared the signaling mechanisms employed by TSLP and
      IL-7. Proliferation of a factor-dependent pre-B cell line (NAG8/7) in response to
      either TSLP or IL-7 was inhibited by anti-IL-7R alpha mAbs, suggesting that the
      functional TSLP receptor complex uses IL-7R alpha. In contrast, three different
      Abs to the common cytokine receptor gamma-chain had no effect on the response of
      these cells to TSLP, indicating that the functional TSLP receptor complex does
      not use the common cytokine receptor gamma-chain. Both cytokines induced
      activation of Stat5, but only IL-7 induced activation of the Janus family kinases
      Jak1 and Jak3. In fact, TSLP failed to activate any of the four known Janus
      family kinases, suggesting that Stat5 phosphorylation is mediated by a novel
      mechanism. Taken together, these data support the idea that TSLP can make unique
      contributions to B lymphopoiesis and indicate that it does so by mechanisms
      distinct from IL-7.

PMID- 9916687
TI  - Presence of pentoxifylline during T cell priming increases clonal frequencies in
      secondary proliferative responses and inhibits apoptosis.
AB  - Naive T cells appear to be primed by specific Ag to differentiate into either
      effectors or memory cells. We have been analyzing the factors involved in this
      differential commitment in the priming of alloresponsive human T cells in vitro
      and have shown that the presence of a phosphodiesterase inhibitor, pentoxifylline
      (POX), during priming results in a decrease in the primary response and
      enhancement in the secondary proliferative response. We now show that the POX
      mediated effect can be mimicked by dibutyryl cAMP. The secondary response
      enhancement is due to the effects of POX on the T cells rather than the APCs,
      because even fixed APCs can prime T cells in the presence of POX. POX affects T
      cells directly by increasing clonal frequency rather than the burst size of the
      secondary responders. The known inhibition of IL-2 production by POX is not
      responsible for this effect, because exogenous IL-2 supplementation does not
      block it. The presence of POX during priming alters the outcome of T cell
      activation, resulting in a lower frequency of cells expressing IL-2R alpha (CD25)
      and a decrease in their subsequent apoptosis, and this antiapoptotic effect is
      consistent with the enhanced commitment of T cells to secondary responsiveness by
      POX.

PMID- 9916688
TI  - Antigen recognition influences transendothelial migration of CD4+ T cells.
AB  - The functional significance of MHC class II expression by vascular endothelial
      cells remains obscure. In this study the possibility that Ag presentation by
      endothelial cells (EC) influences T cell transmigration, facilitating the
      recruitment of Ag-specific T cells into tissues, was investigated. The
      frequencies of T cells with specificity for an HLA-DR alloantigen, or for the
      recall Ag tetanus toxoid (TT), were measured in peripheral blood CD45RO+ (memory)
      CD4+ T cells before and after transmigration through gamma-IFN-treated EC
      monolayers. Frequencies of anti-DR17, IL-2-secreting T cells were fourfold higher
      in the T cells that transmigrated through a monolayer of DR17-expressing EC.
      Similar increases were seen in TT-specific, DR7-restricted T cells that
      transmigrated through TT-pulsed, DR7-expressing EC. To examine more directly the
      effects of cognate recognition of Ag presented by EC, T cell clones were used.
      For clones that proliferated in a costimulation-independent manner to Ag
      presented by EC, cognate recognition arrested transmigration. In contrast, Ag
      presentation by EC to B7-dependent T cell clones, which do not proliferate
      following cognate recognition of EC, enhanced the rate of transendothelial
      migration. These data suggest that Ag presentation by EC may serve to augment the
      recruitment of Ag-specific T cells into tissues and that proliferation and
      transmigration are mutually exclusive T cell responses.

PMID- 9916689
TI  - T cell responses to heat-shock protein 60: differential responses by CD4+ T cell
      subsets according to their expression of CD45 isotypes.
AB  - We demonstrate that human T lymphocytes proliferate in vitro to highly purified
      human heat-shock protein 60 (Hu.hsp60). The response to this self Ag was confined
      to the CD45RA+ RO- T cell subset, with minimal responses by adult CD45RA- RO+ T
      cells. Experiments using keyhole limpet hemocyanin as a prototypic novel Ag, or
      tetanus toxoid as a recall Ag, were consistent with the notion that CD45RA+ RO-
      and CD45RA- RO+ T cell subsets can be designated as naive and memory cells,
      respectively; thus, responses to Hu.hsp60 were confined to the putative naive
      subset. In contrast, both CD45RA+ RO- and CD45RA- RO+ T cell populations
      proliferated to bacterial hsp60 from Mycobacterium leprae, Escherichia coli, or
      Chlamydia trachomatis. However, only CD45RA- RO+ (memory) T cells responded to a
      mycobacterial hsp60-derived peptide previously defined as a major bacteria
      specific epitope. Experiments with cord blood T cells, which are CD45RA+ RO- and
      can be considered truly naive, showed that the peptide could elicit responses
      from naive T cells in vitro; cord blood cells also responded to Hu.hsp60. Since
      bacterial hsp60 Ags contain both conserved and nonconserved epitopes, we
      speculate that in vivo challenge with bacterial hsp60 will activate T cells
      capable of seeing either type of epitope, but only those that see nonconserved
      epitopes maintain the CD45RA- RO+ memory phenotype. However, T cells recognizing
      conserved epitopes, while not apparently being recruited to the memory pool, may
      nevertheless play a role in immunoregulation, particularly in the context of
      inflammation, when expression of Hu.hsp60 is increased.

PMID- 9916690
TI  - Maturation of CD4+ lymphocytes in the aged microenvironment results in a memory
      enriched population.
AB  - With advancing age the CD4+ T lymphocyte compartment becomes enriched for memory
      cells in both humans and experimental animals. Although it has been assumed that
      the shift from a naive to a memory-dominant population is due to a lifetime of
      antigenic exposure and selection as well as a loss of naive cell input due to
      reduced thymopoiesis, the present data suggest that the aged microenvironment
      influences the maturation of newly produced CD4+ T cells. In two models, aged and
      young mice were compared for the ability to reconstitute their peripheral CD4+ T
      cell pools following depletion, and both age groups were found to be competent to
      renew this population. However, the phenotype and lymphokine profile of
      populations arising in aged animals were distinctly different from those in the
      young mice. In contrast to the expectation that depletion and reconstitution
      might give rise to a naive-dominant T cell pool, aged mice reconstituted a
      population nearly indistinguishable from that found in control age-matched
      individuals. The majority of the CD4+ pool were CD44(high) CD45RB(low) Mel
      14(low) and upon activation with anti-CD3 these CD4+ T cells produced mRNA for IL
      2, IL-4, IL-5, and IFN-gamma. In aged bone marrow-transplanted mice, the same
      phenotypic profile and cytokine mRNA pattern were found in CD4+ T cells of host
      and donor origin. In contrast, the majority of CD4+ T cells in young
      reconstituted mice were CD44(low) CD45RB(high) Mel-14(high). These lymphocytes,
      when activated, produced high levels of mRNA for IL-2, with little or no IL-4, IL
      5, or IFN-gamma mRNA.

PMID- 9916692
TI  - Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF
      responsive element of the murine monocyte chemoattractant-1 gene.
AB  - TNF-alpha transcriptionally regulates murine monocyte chemoattractant protein-1
      (MCP-1) expression. Three approaches were used to determine the mechanism by
      which TNF regulates MCP-1. Mutation analysis showed that two distal kappa B
      sites, a novel dimethylsulfate-hypersensitive sequence, and a promoter proximal
      SP-1 site were required for TNF induction. Although the kappa B sites and the
      hypersensitive sequence function as a NF-kappa B-mediated enhancer, regulating
      induction by TNF, stereospecific alignment of the kappa B sites was not critical.
      Trans-activation studies conducted by cotransfection of p50 and/or p65 expression
      vectors with MCP-1 constructions showed that TNF regulates MCP-1 through NF-kappa
      B. Examination of MCP-1 induction in NF-kappa B-disrupted embryonic fibroblasts
      showed that p65 was necessary for both the induction and the TNF-induced protein
      occupancy of the enhancer in vivo. The action of the antioxidant inhibitor of NF
      kappa B activation, pyrrolidine dithiocarbamate, in wild-type and NF-kappa B
      mutant cells was examined. The results suggested that TNF activates NF-kappa B
      through both pyrrolidine dithiocarbamate-sensitive and -insensitive mechanisms.
      This study illustrates the crucial role for NF-kappa B p65 in the induction of
      the MCP-1 gene by TNF and in the assembly of a NF-kappa B dependent enhancer in
      vivo.

PMID- 9916693
TI  - Quantitative analysis of the effect of CD16 ligation on human NK cell
      proliferation.
AB  - CD16 (Fc gammaRIIIA), the low affinity receptor for IgG, is expressed on the
      majority of human peripheral blood NK cells. Ligation of CD16 with mAb or immune
      complexes activates NK cell cytotoxicity and cytokine secretion, and stimulates
      death of activated NK cells by apoptosis. This study uses NK cells labeled with
      the stable intracytoplasmic fluorescent dye 5- and 6-carboxyfluorescein diacetate
      succinimidyl ester to provide quantitative data on the effect of CD16 ligation on
      NK cell division and NK cell survival. When NK cells are cultured with rIL-2 and
      CD16 is ligated, NK cell division is stimulated, but there also is a substantial
      loss of NK progenitor cells. When NK cell proliferation is stimulated by
      coculture with gamma-irradiated MM-170 malignant melanoma cells and rIL-2, CD16
      ligation enhances entry of NK cells into division. In some cases, CD16 ligation
      is essential for NK cell proliferation stimulated by MM-170 cells. In these
      cultures, there is no loss of NK progenitor cells. This study demonstrates that
      CD16 is an activation receptor for NK cell proliferation, and suggests that
      cellular costimulation alters the balance between NK cell death and NK cell
      proliferation stimulated by CD16 ligation.

PMID- 9916691
TI  - The role of LY49 NK cell subsets in the regulation of murine cytomegalovirus
      infections.
AB  - The distributions and functions of NK cell subsets, as defined by the expression
      of Ly49 NK cell receptors, were examined in murine CMV (MCMV)-infected mice. MCMV
      induced a reduction in NK1.1+ cell number in the spleen and an increase in the
      peritoneal exudate cells. Within the splenic NK1.1+ population, proportional
      increases in Ly49A+ and Ly49G2+ cells but decreases in Ly49C+ and Ly49D+ cells
      were observed 3 days post-MCMV infection, but within the peritoneal NK1.1+ cell
      populations there were proportional decreases in Ly49A+ cells and increases in
      Ly49C+, Ly49D+, and Ly49G2+ cells. Lymphocytic choriomeningitis virus did not
      elicit a comparable NK cell subset distribution. Lymphokine-activated killer
      cells were sorted into different Ly49 NK cell subsets and adoptively transferred
      into C57BL/6 suckling mice. Regulation of MCMV synthesis in these suckling mice
      was shown to be an IFN-gamma-dependent, perforin- and Cmv-1-independent process,
      and each NK cell subset mediated anti-viral activity. In adult C57BL/6 mice, the
      control of MCMV in the spleen is mediated by a perforin-dependent mechanism,
      regulated in part by the Cmv-1 gene, which maps closely to the Ly49 family. In
      vivo depletions of either one or two of the Ly49 subsets in adult mice did not
      affect the ability of the residual NK cells to regulate MCMV synthesis. These
      data provide evidence of NK cell subset distribution and function in MCMV
      infection, but no individual subset was required for the Cmv-1-like regulation of
      MCMV synthesis.

PMID- 9916694
TI  - RT1-U: identification of a novel, active, class Ib alloantigen of the rat MHC.
AB  - In common with other mammalian species, the laboratory rat (Rattus norvegicus)
      expresses MHC class I molecules that have been categorized as either classical
      (class Ia) or nonclassical (class Ib). This distinction separates the class Ia
      molecules that play a conventional role in peptide Ag presentation to CD8 T cells
      from the others, whose function is unconventional or undefined. The class Ia
      molecules are encoded by the RT1-A region of the rat MHC, while the RT1-C/E/M
      region encodes up to 60 other class I genes or gene fragments, a number of which
      are known to be expressed (or to be expressible). Here we report upon novel MHC
      class Ib genes of the rat that we have expression cloned using new monoclonal
      alloantibodies and which we term RT1-U. The products detected by these Abs were
      readily identifiable by two-dimensional analysis of immunoprecipitates and were
      shown to be distinct from the class Ia products. Cellular studies of these
      molecules indicate that they function efficiently as targets for cytotoxic
      killing by appropriately raised polyclonal alloreactive CTL populations. The
      sequences of these class Ib genes group together in phylogenetic analysis,
      suggesting a unique locus or family. The combined serological, CTL, and sequence
      data all indicate that these products are genetically polymorphic.

PMID- 9916695
TI  - A single intramuscular injection with an adenovirus-expressing IL-12 protects
      BALB/c mice against Leishmania major infection, while treatment with an IL-4
      expressing vector increases disease susceptibility in B10.D2 mice.
AB  - Experimental infection of the susceptible BALB/c (H-2d) mouse with the
      intracellular parasite Leishmania major induces a predominant Th2-type T cell
      response that eventually leads to death. In contrast, the resistant B10.D2 (H-2d)
      strain develops Th1 cells that control parasite replication and disease. In this
      study, we tested the ability of a recombinant adenovirus vector-expressing IL-12
      to skew the immune response in a Th1 direction and prevent leishmaniasis in
      susceptible mice. We report that BALB/c mice treated with the Ad5IL-12 vector on
      the same day as parasitic challenge are significantly protected against
      leishmaniasis and acquired long-lasting immunity, because upon rechallenge with
      L. major parasites they were resistant to disease. The vector-derived IL-12
      expression was transient and highly localized to the tissue after i.m. injection;
      it caused an increase in the number of Ag-specific IFN-gamma-secreting
      lymphocytes and enhanced NK cell activity in the draining popliteal node. In
      contrast, resistant B10.D2 mice given i.m. injections with a recombinant
      adenovirus-expressing IL-4 displayed greater susceptibility to disease, and
      severe lesions were produced in some of the infected animals. These results
      suggest the potential use of recombinant adenoviruses expressing cytokines as
      potent immunomodulatory agents for the generation of protective immune responses
      against intracellular pathogens.

PMID- 9916696
TI  - Acquired thymic tolerance: role of CTLA4 in the initiation and maintenance of
      tolerance in a clinically relevant autoimmune disease model.
AB  - Injection of Ag into the thymus of adult animals induces specific systemic
      tolerance. The mechanisms of acquired thymic tolerance include anergy and the
      deletion of Ag-specific T cells. Here, we report that anergy to nominal Ag
      induced via acquired thymic tolerance requires CTL-associated Ag 4 (CTLA4)
      engagement. The role of CTLA4 in the induction and maintenance of tolerance was
      then investigated in the murine experimental autoimmune encephalomyelitis model.
      CTLA4 blockade abrogated the induction but not the maintenance phase of acquired
      thymic tolerance induced by intrathymic injection of myelin Ags. In addition,
      CTLA4 blockade had a restricted window of action after priming with Ag, which is
      consistent with the expression patterns of CTLA4 in vivo. We conclude that: 1)
      the induction of acquired thymic tolerance requires signaling through CTLA4 and
      2) CTLA4 does not appear to be required for the maintenance of acquired thymic
      tolerance. This is the first report documenting the role of a CTLA4 negative
      signaling pathway in the induction of tolerance in an autoimmune disease model.

PMID- 9916697
TI  - Functional characteristics and survival requirements of memory CD4+ T lymphocytes
      in vivo.
AB  - The phenotypic and functional characteristics of Ag-specific memory CD4+
      lymphocytes are poorly defined. To examine the properties and cytokine
      responsiveness of these cells, we have developed an adoptive transfer system
      using in vitro-activated T cells expressing the DO.11 transgenic TCR specific for
      OVA(323-339)+ I-Ad. In vitro-activated DO.11 CD4+ cells exhibit comparable
      survival patterns at 1, 6, and 10 wk after adoptive transfer, indicating that a
      stable population of memory cells has been generated. In the absence of Ag,
      previously activated T cells survive longer than their naive counterparts in
      vivo, rapidly revert to a partially naive phenotype, and maintain their effector
      cytokine profile. The DO.11 CD4+ memory cells are capable of proliferating in
      response to IL-2 and IL-4, while naive DO.11 CD4+ cells exhibit no such
      proliferative responses.

PMID- 9916698
TI  - Evidence that an OX-2-positive cell can inhibit the stimulation of type 1
      cytokine production by bone marrow-derived B7-1 (and B7-2)-positive dendritic
      cells.
AB  - We reported that hepatic mononuclear, nonparenchymal cells (NPC) can inhibit the
      immune response seen when allogeneic C57BL/6 dendritic cells (DC) are incubated
      with C3H spleen responder cells. Cells derived from these cultures transfer
      increased survival of C57BL/6 renal allografts in C3H mice. We also found that
      increased expression of OX-2 on DC was associated with inhibition of cytokine
      production and renal allograft rejection. We explored whether inhibition by
      hepatic NPC was a function of OX-2 expression by these cells. Fresh C57BL/6
      spleen-derived DC were cultured with C3H spleen responder cells and other
      putative coregulatory cells. The latter were derived from fresh C3H or C57BL/6
      liver NPC, or from C3H or C57BL/6 mice treated for 10 days by i.v. infusion of
      human Flt3 ligand. Different populations of murine bone marrow-derived DC from
      cultures of bone marrow with IL-4 plus granulocyte-macrophage-CSF were also used
      as a source of putative regulator cells. Supernatants of all stimulated cultures
      were examined for functional expression of different cytokines (IL-2, IL-4, IFN
      gamma, and TGFbeta). We found that fresh C57BL/6 splenic DC induced IL-2, not IL
      4, production. Cells from the sources indicated inhibited IL-2 and IFN-gamma
      production and promoted IL-4 and TGFbeta production. Inhibition was associated
      with increased expression of OX-2 on these cells, as defined by semiquantitative
      PCR and FACS analysis. By size fractionation, cells expressing OX-2 were a
      subpopulation of NLDC145+ cells. Our data imply a role for cells expressing OX-2
      in the regulation of induction of cytokine production by conventional
      allostimulatory DC.

PMID- 9916699
TI  - Role of Bcl-2 in alpha beta T cell development in mice deficient in the common
      cytokine receptor gamma-chain: the requirement for Bcl-2 differs depending on the
      TCR/MHC affinity.
AB  - Mice lacking the common cytokine receptor gamma-chain (gamma c) exhibit severely
      compromised T cell development, with diminished Bcl-2 expression in mature (CD4+
      or CD8+) thymocytes and peripheral T cells. Enforced expression of Bcl-2 in these
      mice partially rescued alpha beta T cell development but not gamma delta T cell
      development. Transgenic expression of the OVA-specific DO11.10 (DO10) TCR also
      could modestly increase thymocyte numbers, and T cells expressing the transgenic
      TCR (KJ1-26+ T cells) were found in the periphery. Interestingly, the presence of
      KJ1-26+ T cells was dependent on the MHC background and was seen in the moderate
      affinity H-2d/d background but not in the higher affinity H-2d/b background in
      gamma c-deficient mice. In contrast, KJ1-26+ T cells exist in the periphery in
      both the H-2d/d and H-2d/b backgrounds in DO10 transgenic gamma c wild-type mice.
      These results suggest that the importance of gamma c-dependent signals for T cell
      development differs depending on the affinity of TCR for MHC. Moreover, enforced
      expression of Bcl-2 had a much greater effect on the development of gamma c
      deficient T cells expressing the DO10 TCR in the high affinity H-2d/b background
      than in the H-2d/d background, suggesting that gamma c-dependent Bcl-2 expression
      influences T cell development in a TCR/MHC-dependent manner.

PMID- 9916700
TI  - IFN-gamma down-regulates MHC expression and antigen processing in a human B cell
      line.
AB  - IFN-gamma is a crucial mediator in the induction of cell-mediated Th1-type
      responses but is predominantly a negative regulator of B cell differentiation and
      proliferation. This cytokine is therefore a key factor in determining Th1 vs Th2
      differentiation. This study investigates the action of IFN-gamma in modulation of
      HLA-DR expression and Ag presentation by EBV-transformed human B cell lines. In
      contrast to its action on the monocyte/macrophage, IFN-gamma down-regulates
      surface MHC expression on these B cells, and this regulation is
      posttranscriptional. In parallel with MHC down-regulation, there is a reduced
      capability to process and present exogenous protein and peptide Ag to T cell
      hybridomas. IFN-gamma does not change the rates of fluid phase endocytosis or
      exocytosis in this model system but correlates with an up-regulation of the
      lysosomal enzymes cathepsins B and D.

PMID- 9916702
TI  - Differential requirement of IFN consensus sequence binding protein for the
      production of IL-12 and induction of Th1-type cells in response to IFN-gamma.
AB  - IFN-gamma exerts multiple biological activities in the modulation of immune
      responses by the induction of transcription factors. One transcriptional factor
      of the IFN regulatory factor family found to be critical in regulating IL-12
      dependent IFN-gamma production in vivo following infectious challenge has been
      designated IFN consensus sequence-binding protein (ICSBP). In this study, the
      role of ICSBP in regulating type 1 responses to T cell-specific stimulation in
      vitro was assessed. Total splenocytes from ICSBP-/- mice stimulated with soluble
      anti-CD3 were markedly impaired in the production of IFN-gamma compared with
      similarly stimulated cells from ICSBP+/+ mice. Consistent with the decrease in
      IFN-gamma production, splenocytes from ICSBP-/- mice stimulated with anti-CD3 in
      the presence or absence of IFN-gamma or a soluble CD40 ligand agonist failed to
      produce IL-12 p40 and IL-12 p70 protein; however, the deficient production of IFN
      gamma from ICSBP-/- mice could be restored by the addition of anti-CD28 Ab in an
      IL-12-independent manner. In contrast to the previous data, production of IFN
      gamma from naive CD4+/LECAM-1high cells of ICSBP-/- mice that had been primed in
      vitro with anti-CD3 was similar to or greater than that of ICSBP+/+ controls. In
      addition, the presence of IFN-gamma in priming cultures enhanced both priming for
      IFN-gamma and IL-12 responsiveness from ICSBP-/- CD4+ T cells. Overall, these
      results provide evidence that ICSBP is differentially required for the ability of
      IFN-gamma to regulate type 1 cytokine responses from APCs and CD4+ T cells.

PMID- 9916701
TI  - Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but
      inhibit IL-2 production and proliferation.
AB  - Galectin-1 is an endogenous lectin expressed by thymic and lymph node stromal
      cells at sites of Ag presentation and T cell death during normal development. It
      is known to have immunomodulatory activity in vivo and can induce apoptosis in
      thymocytes and activated T cells (1-3). Here we demonstrate that galectin-1
      stimulation cooperates with TCR engagement to induce apoptosis, but antagonizes
      TCR-induced IL-2 production and proliferation in a murine T cell hybridoma and
      freshly isolated mouse thymocytes, respectively. Although CD4+ CD8+ double
      positive cells are the primary thymic subpopulation susceptible to galectin-1
      treatment alone, concomitant CD3 engagement and galectin-1 stimulation broaden
      susceptible thymocyte subpopulations to include a subset of each CD4- CD8-, CD4+
      CD8+, CD4- CD8+, and CD4+ CD8- subpopulations. Furthermore, CD3 engagement
      cooperates with suboptimal galectin-1 stimulation to enhance cell death in the
      CD4+ CD8+ subpopulation. Galectin-1 stimulation is shown to synergize with TCR
      engagement to dramatically and specifically enhance extracellular signal
      regulated kinase-2 (ERK-2) activation, though it does not uniformly enhance TCR
      induced tyrosine phosphorylation. Unlike TCR-induced IL-2 production,
      TCR/galectin-1-induced apoptosis is not modulated by the expression of kinase
      inactive or constitutively activated Lck. These data support a role for galectin
      1 as a potent modulator of TCR signals and functions and indicate that individual
      TCR-induced signals can be independently modulated to specifically affect
      distinct TCR functions.

PMID- 9916703
TI  - Persistence of autoreactive T cell drive is required to elicit anti-chromatin
      antibodies in a murine model of drug-induced lupus.
AB  - Long-term treatment with procainamide and numerous other medications is
      occasionally associated with the development of drug-induced lupus. We recently
      established a murine model for this syndrome by disrupting central T cell
      tolerance. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a
      reactive metabolite of procainamide, into (C57BL/6 x DBA/2)F1 mice resulted in
      the appearance of chromatin-reactive T cells and anti-chromatin autoantibodies.
      The current study explores in this model the role of autoreactive T cells in
      autoantibody production and examines why autoantibodies after a single
      intrathymic drug injection were much more limited in isotype and specificity.
      Injection of as few as 5000 chromatin-reactive T cells into naive, syngeneic mice
      induced a rapid IgM anti-denatured DNA response, while injection of at least 100
      fold greater number of activated T cells was required for induction of IgG anti
      chromatin Abs, suggesting that small numbers of autoreactive T cells can be
      homeostatically controlled. Mice subjected to a single intrathymic PAHA injection
      after receiving splenic B cells from an intrathymic PAHA-injected syngeneic donor
      also developed anti-chromatin Abs, but adoptive transfer of similarly primed T
      cells or of B cells without intrathymic PAHA injection of the recipient failed to
      produce an anti-chromatin response. However, anti-chromatin Abs developed after a
      single intrathymic PAHA injection in Fas-deficient C57BL/6-lpr/lpr mice,
      suggesting that activation-induced cell death limited autoimmunity in normal
      mice. Taken together, these results imply that chromatin-reactive T cells
      produced by intrathymic PAHA created a B cell population primed to somatically
      mutate and Ig class switch when subjected to a heavy load or second wave of
      autoreactive T cells.

PMID- 9916704
TI  - Deficiency of IL-5 receptor alpha-chain selectively influences the development of
      the common mucosal immune system independent IgA-producing B-1 cell in mucosa
      associated tissues.
AB  - Deletion of IL-5R alpha-chain (IL-5R alpha-/-) selectively influenced the mucosal
      IgA responses in vivo. While levels of IgA in mucosal secretions were more
      reduced in IL-5R alpha-/- mice than in wild-type mice, the levels of IgA in serum
      were not changed. The frequency of IgA-producing cells was reduced in mucosal
      effector sites (e.g., intestinal lamina propria and nasal passage), but not in
      inductive sites such as Payer's patches and nasal-associated lymphoreticular
      tissues in IL-5R alpha-/- mice. IgA-committed (surface IgA+; sIgA+) B-1 cells
      mainly resided in mucosal effector tissues, while conventional sIgA+ B (B-2)
      cells formed in mucosal inductive sites of wild-type mice. In contrast, in the
      effector tissue of IL-5R alpha-/- mice, sIgA+ B-1 cells, but not sIgA+ B-2 cells
      in the inductive site, were significantly reduced. IL-5R alpha was more expressed
      on sIgA+ B-1 cells than was IL-6R, while both IL-5R alpha and IL-6R were
      expressed on sIgA+ B-2 cells in wild-type mice. sIgA+ B-1 cells produced high
      levels of IgA with rIL-5 rather than of rIL-6 in vitro. Taken together, the
      findings suggest that the IL-5/IL-5R signaling pathway is critically important
      for the development of common mucosal immune system independent sIgA+ B-1 cell in
      mucosal effector tissues in vivo.

PMID- 9916705
TI  - Critical requirement for aspartic acid at position 82 of myelin basic protein 73
      86 for recruitment of V beta 8.2+ T cells and encephalitogenicity in the Lewis
      rat.
AB  - We synthesized single amino acid-substituted peptide analogues of guinea pig
      myelin basic protein (MBP) 73-86 to study the importance of aspartic acid at
      residue 82 (QKSQRSQDENPV), which previous reports have suggested is a critical
      TCR contact residue. Whereas the wild-type 73-86 peptide elicited severe
      experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, none of the
      peptide analogues with substitutions at position 82 were capable of inducing EAE.
      The inability to cause EAE was not due to a failure to bind MHC or to elicit T
      cell proliferation and cytokine secretion. T cells specific for MBP73-86 did not
      cross-react with any of the analogues tested, further indicating the importance
      of this residue in T cell responses to 73-86. Analysis by flow cytometry showed
      that only the wild-type 73-86 peptide was capable of recruiting V beta 8.2+ T
      cells, which have been shown previously to be important for disease induction.
      Reduced expression of the V beta 8.2 TCR was also seen in Lewis rats protected
      from EAE by coimmunization of MBP73-86 with 73-86(82D-->A), despite an increase
      in cytokine production when both peptides were present during in vitro culture.
      The data indicate that aspartic acid 82 is a critical TCR contact residue and is
      required for the recruitment of V beta 8.2+ T cells and the encephalitogenic
      activity of MBP73-86.

PMID- 9916706
TI  - Multiple signal transduction pathways regulate TNF-induced actin reorganization
      in macrophages: inhibition of Cdc42-mediated filopodium formation by TNF.
AB  - TNF is known to regulate macrophage (Mphi) migration, but the signaling pathways
      mediating this response have not been established. Here we report that
      stimulation of the 55-kDa TNF receptor (TNFR-1) induced an overall decrease in
      filamentous actin (F-actin), inhibited CSF-1- and Cdc42-dependent filopodium
      formation, and stimulated macropinocytosis. Using a panel of TNFR-1 mutants, the
      regions of the receptor required for each of these responses were mapped. The
      decrease in F-actin required both the death domain and the membrane proximal part
      of the receptor, whereas inhibition of filopodium formation and increased
      pinocytosis were only dependent upon a functional death domain. When the TNF
      induced decrease in F-actin was inhibited using either receptor mutants or the
      compound D609, TNF-stimulated actin reorganization at the cell cortex became
      apparent. This activity was dependent upon the FAN-binding region of TNFR-1. We
      conclude that different domains of TNFR-1 mediate distinct changes in the Mphi
      cytoskeleton, and that the ability of TNF to inhibit Mphi chemotaxis may be due
      to decreased filopodium formation downstream of Cdc42.

PMID- 9916707
TI  - Orientation of the Ig domains of CD8 alpha beta relative to MHC class I.
AB  - The cell surface glycoprotein CD8 functions as a coreceptor with the TCR for
      interaction with MHC class I. The cocrystal structure of the CD8 alpha alpha-MHC
      complex showed that one CD8 Ig domain provided the majority of the contact with
      MHC class I and that residue R4 of that domain contacted the alpha2 domain of MHC
      class I. We previously showed by mutational analysis that this residue was
      critical for binding to MHC class I. To determine which of the Ig domains for the
      CD8 alpha beta heterodimer would make the most contact with class I MHC, we
      expressed single-chain or dimeric forms of CD8 on COS-7 cells and measured the
      adhesion of MHC class I positive cells. We found that when one of the R4 residues
      was mutated in a CD8 alpha alpha homodimer binding comparable to that of wild
      type was observed, whereas a double R4 mutant severely impaired binding. However,
      when mutant CD8 alpha (R4K) was coexpressed with wild-type CD8 beta, binding was
      not observed. These results support the model in which it is CD8 alpha, not CD8
      beta, that is making the most of the contact with MHC class I, including the
      alpha 2 domain. In addition, they demonstrate that a single-chain form of CD8
      alpha alpha can bind to MHC class I.

PMID- 9916708
TI  - Novel splicing of the human MHC-encoded peptide transporter confers unique
      properties.
AB  - Presentation of intracellularly derived antigenic peptides to T cells requires
      their assembly together with MHC class I molecules in the endoplasmic reticulum
      (ER). Such peptides are delivered to the ER by an MHC-encoded transporter
      composed of TAP1 and TAP2 protein delivery. Here, the first alternative splicing
      of Tap2 is described. The human splice variant, termed Tap2iso, lacks exon 11 and
      original 3' untranslated region and contains a newly identified exon 12 and 3'
      untranslated region. The full-length Tap2iso cDNA (2496 bp) predicts a protein of
      653 amino acids. Tap2iso mRNA was normally coexpressed with Tap2 mRNA in all
      human lymphocyte cell lines examined. Function of TAP2iso was evaluated at
      multilevel in TAP1/2iso and TAP1/2 cotransfected T2 cells, a mutant cell line
      deplete of endogenous Tap gene products. The TAP1-TAP2iso transporter facilitated
      the maturation of MHC class I molecules in the ER and restored surface expression
      of class I. Importantly, TAP1-TAP2iso transporters expressed in T2 cells
      exhibited distinct and opposing influences on peptide selectivities, at times
      exceeding 30-fold differences in competition experiments and attributable to
      diversity in the 3'-COOH tail. The common coexpression of an alternative splice
      product of the Tap2 gene may contribute to broaden immune diversity, a mechanism
      previously described to occur predominantly at the level of the TCR and MHC class
      I gene products.

PMID- 9916709
TI  - T cell priming enhances IL-4 gene expression by increasing nuclear factor of
      activated T cells.
AB  - The repetitive activation of T cells (priming) enhances the expression of many
      cytokines, such as IL-4, but not others, such as IL-2. Molecular mechanisms
      underlying selective expression of cytokines by T cells remain poorly understood.
      Here we show that priming of CD4 T cells selectively enhances IL-4 expression
      relative to IL-2 expression by a transcriptional mechanism involving nuclear
      factor of activated T cells (NFAT) proteins. As detected by in vivo footprinting,
      priming markedly increases the activation-dependent engagement of the P0 and P1
      NFAT-binding elements of the IL-4 promoter. Moreover, each proximal P element is
      essential for optimal IL-4 promoter activity. Activated primed CD4 T cells
      contain more NFAT1 and support greater NFAT-directed transcription than unprimed
      CD4 T cells, while activator protein 1 binding and activator protein 1-mediated
      transcription by both cell types is similar. Increased expression of wild-type
      NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells,
      suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type.
      Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4
      promoter activity in primed CD4 T cells and confirming the importance of
      endogenous NFAT to increased IL-4 gene expression by effector T cells. NFAT1
      appears to be the major NFAT family member responsible for the initial increased
      expression of IL-4 by primed CD4 T cells.

PMID- 9916710
TI  - Alternative splicing and hypermutation of a nonproductively rearranged TCR alpha
      chain in a T cell hybridoma.
AB  - Like Ig genes, TCR genes are formed by somatic rearrangements of noncontiguous
      genomic V, J, and C regions. Unlike Ig genes, somatic hypermutation of TCR V
      regions is an infrequent event. We describe the occurrence of spontaneous
      hypermutation in a nonproductively rearranged TCR alpha-chain gene in a clonal T
      cell hybridoma that had lost its productively rearranged alpha-chain. The
      mutating hybridoma was eventually supplanted in culture by a nonmutating variant
      that had restored an open reading frame in the nonproductively rearranged TCR
      alpha-chain through the use of cryptic splice sites in the V alpha region.
      Evidence is presented for the presence of cDNA reverse transcripts of the TCR
      alpha-chain within the hybridoma, suggesting a role for reverse transcriptase in
      the generation of mutations.

PMID- 9916711
TI  - The extracellular domain of the zeta-chain is essential for TCR function.
AB  - The zeta-chain homodimer is a key component in the TCR complex and exerts its
      function through its cytoplasmic immunoreceptor-tyrosine activation motif (1).
      The zeta-chain extracellular (EC) domain is highly conserved; however, its
      functional and structural contributions to the TCR signaling have not been
      elucidated. We show that the EC domain of the zeta homodimer is essential for TCR
      surface expression. To gain a more detailed structural and functional information
      about the zeta-chain EC domain, we applied a cysteine scanning mutagenesis to
      conserved amino acids of the short domain. The results showed that the interchain
      disulfide bridge can be displaced by seven or eight amino acids along the EC
      domain. The TCR signaling efficacy was dramatically reduced during peptide/MHC
      engagement in the zeta mutants containing the displaced disulfide bond. These
      signaling defective zeta mutants produced an unconventional early tyrosine
      phosphorylation pattern. While the tyrosine phosphorylated forms of zeta (p21 and
      p23) could be observed during Ag stimulation, downstream signaling events such as
      the generation of phospho-p36, higher m.w. forms of phospho-zeta, and phospho
      zeta/ZAP-70 complexes were impaired. Together these results suggest an important
      function of the phylogenetically conserved zeta-EC domain.

PMID- 9916712
TI  - IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing
      transcription of the class II transactivator gene.
AB  - Class II MHC Ags are critical for the initiation of immune responses by
      presenting Ag to T lymphocytes, leading to their activation and differentiation.
      The transcriptional activation of class II MHC genes requires the induction of
      the class II transactivator (CIITA) protein, a master regulator that is essential
      for both constitutive and IFN-gamma-inducible class II MHC expression. The
      cytokine IL-1beta has been shown to inhibit IFN-gamma-induced class II MHC
      expression in various cell types. We investigated the underlying mechanism of
      this inhibitory effect of IL-1beta using human astroglioma cell lines. Our
      findings demonstrate that IL-1beta prevents the expression of class II MHC mRNA
      and protein upon treatment with IFN-gamma. Furthermore, we demonstrate that IFN
      gamma induction of CIITA mRNA expression is inhibited by treatment of cells with
      IL-1beta. IL-1beta suppressed IFN-gamma activation of the type IV CIITA promoter
      in astroglioma cells, indicating that the inhibitory influence of IL-1beta is
      mediated by inhibition of CIITA transcription. IL-1beta did not interfere with
      IFN-gamma receptor signal transduction, since tyrosine phosphorylation, nuclear
      translocation, and DNA binding of STAT-1alpha to an IFN-gamma activation sequence
      of the type IV CIITA promoter were not affected by IL-1beta. As well, IL-1beta
      treatment did not affect the ability of IFN-gamma-induced interferon-regulatory
      factor-1 (IRF-1) to bind the IRF-1 element within the type IV CIITA promoter.
      This study suggests that IL-1beta may play a role in regulating immunoreactivity
      by inhibiting transcription of the CIITA gene, thereby reducing subsequent class
      II MHC expression.

PMID- 9916713
TI  - Conserved residues amino-terminal of cytoplasmic tyrosines contribute to the SHP
      1-mediated inhibitory function of killer cell Ig-like receptors.
AB  - The sequence I/VxYxxL, often referred to as an immunoreceptor tyrosine-based
      inhibition motif (ITIM), binds to the C-terminal Src homology 2 domain of the
      tyrosine phosphatase SHP-1. Conserved residues N-terminal of the tyrosine are not
      ordinarily found in other Src homology 2 domain binding motifs. The inhibitory
      forms of killer cell Ig-like receptors (KIR) contain two ITIMs. The role of each
      ITIM, and of the conserved residues upstream of the tyrosine, in the inhibition
      of NK cells was tested by vaccinia virus-mediated expression of mutant KIRs.
      Substitution of the tyrosine in the membrane-proximal ITIM abrogated the ability
      of KIR to block Ab-dependent cellular cytotoxicity, whereas mutation of the
      membrane-distal ITIM tyrosine had little effect. Substitution of the conserved
      hydrophobic amino acid that was located two residues N-terminal to the tyrosine
      weakened, but did not eliminate, the function of the receptor. In contrast, these
      substitutions drastically reduced the amount of SHP-1 immunoprecipitated with
      KIR, suggesting that weak interactions with SHP-1 may be sufficient for
      inhibition.

PMID- 9916714
TI  - The mechanism of chromosome 7 inversion in human lymphocytes expressing chimeric
      gamma beta TCR.
AB  - Functional chimeric TCR chains, encoded by V gamma J gamma C beta or V gamma J
      beta C beta hybrid gene TCR, are expressed at the surface of a small fraction of
      alpha beta T lymphocytes in healthy individuals. Their frequency is dramatically
      increased in patients with ataxia-telangiectasia, a syndrome associated with
      inherited genomic instability. As the TCR gamma and beta loci are in an inverted
      orientation on chromosome 7, the generation of such hybrid genes requires at
      least an inversion event. Until now, neither the sequences involved in this
      genetic mechanism nor the number of recombinations leading to the formation of
      functional transcriptional units have been characterized. In this manuscript, we
      demonstrate that at least two rearrangements, involving classical recombination
      signal sequence and the V(D)J recombinase complex, lead to the formation of
      productive hybrid genes. A primary inversion 7 event between D beta and J gamma
      genic segments generates C gamma V beta and C beta V gamma hybrid loci. Within
      the C gamma V beta locus, secondary rearrangements between V gamma and J gamma or
      V gamma and J beta elements generate functional genes. Besides, our results
      suggest that secondary rearrangements were blocked in the C beta V gamma locus of
      normal but not ataxia-telangiectasia T lymphocytes. We also provide formal
      evidence that the same D beta-3' recombination signal sequence can be used in
      successive rearrangements with J gamma and J beta genic segments, thus showing
      that a signal joint has been involved in a secondary recombination event.

PMID- 9916715
TI  - A role for RAD51 in the generation of immunoglobulin gene diversity in rabbits.
AB  - Ig VDJ genes in rabbit somatically diversify by both hyperpointmutation and gene
      conversion. To elucidate the mechanism of gene conversion of IgH genes, we cloned
      a rabbit homologue of RAD51, a gene involved in gene conversion in Saccharomyces
      cerevisiae (yeast), and tested whether it could complement a yeast rad51 mutant
      deficient in recombination repair. We found that rabbit RAD51 partially
      complemented the defect in switching mating types by gene conversion as well as
      in DNA double-strand break repair after gamma-irradiation. Further, by Western
      blot analysis, we found that levels of Rad51 were higher in appendix-derived B
      lymphocytes of 6-wk-old rabbits, a time at which IgH genes diversify by somatic
      gene conversion. We suggest that Rad51 is involved in somatic gene conversion of
      rabbit Ig genes.

PMID- 9916716
TI  - IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma
      formation and IgE responses induced by Schistosoma mansoni eggs.
AB  - Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated
      inflammatory response associated with dominant Th2-type cytokine expression,
      tissue eosinophilia, and high levels of serum IgE. In the present study, we show
      that in vivo blockade of the Th2 cytokine IL-13, using soluble IL-13R alpha2-Fc
      fusion protein, significantly reduced the size of pulmonary granulomas in
      unsensitized as well as egg-sensitized mice. Blocking IL-13 also significantly
      reduced total serum IgE levels. Interestingly, however, IL-13 blockade did not
      affect the evolving egg-induced Th2-type cytokine response. IL-4, IL-5, as well
      as IL-13 responses were indistinguishable in control-Fc- and soluble IL-13R
      alpha2-Fc fusion protein-treated animals. The smaller granulomas were also
      phenotypically like the control Fc-treated mice, displaying a similar eosinophil
      content. Additional studies in IL-4-deficient mice demonstrated that IL-13 was
      produced, but at much lower levels than in wild-type mice, while IL-4 expression
      was completely independent of IL-13. Moreover, while granuloma formation was
      partially reduced in IL-4-deficient mice, blocking IL-13 in these animals almost
      completely abrogated granuloma development and the pulmonary eosinophilia, while
      it simultaneously increased IFN-gamma production. Together, these data
      demonstrate that IL-13 serves as an important mediator of Th2-mediated
      inflammation and plays a role in eliciting IgE responses triggered by schistosome
      eggs.

PMID- 9916717
TI  - Suppression of host immune response by the core protein of hepatitis C virus:
      possible implications for hepatitis C virus persistence.
AB  - Hepatitis C virus (HCV) is a major human pathogen causing mild to severe liver
      disease worldwide. This positive strand RNA virus is remarkably efficient at
      establishing chronic infections. Although a high rate of genetic variability may
      facilitate viral escape and persistence in the face of Ag-specific immune
      responses, HCV may also encode proteins that facilitate evasion of immunological
      surveillance. To address the latter possibility, we examined the influence of
      specific HCV gene products on the host immune response to vaccinia virus in a
      murine model. Various vaccinia/HCV recombinants expressing different regions of
      the HCV polyprotein were used for i.p. inoculation of BALB/c mice. Surprisingly,
      a recombinant expressing the N-terminal half of the polyprotein (including the
      structural proteins, p7, NS2, and a portion of NS3; vHCV-S) led to a dose
      dependent increase in mortality. Increased mortality was not observed for a
      recombinant expressing the majority of the nonstructural region or for a negative
      control virus expressing the beta-galactosidase protein. Examination of T cell
      responses in these mice revealed a marked suppression of vaccinia-specific CTL
      responses and a depressed production of IFN-gamma and IL-2. By using a series of
      vaccinia/HCV recombinants, we found that the HCV core protein was sufficient for
      immunosuppression, prolonged viremia, and increased mortality. These results
      suggest that the HCV core protein plays an important role in the establishment
      and maintenance of HCV infection by suppressing host immune responses, in
      particular the generation of virus-specific CTLs.

PMID- 9916718
TI  - Regulation and functional involvement of macrophage scavenger receptor MARCO in
      clearance of bacteria in vivo.
AB  - The scavenger receptors expressed by macrophages are thought to play an important
      role in the immune response against bacteria by mediating binding and
      phagocytosis. A novel member of the class A scavenger receptor family, macrophage
      receptor with collagenous structure (MARCO), has recently been identified. In
      this study we have generated a panel of mAbs with specificities for different
      domains of this receptor. Two of those reacting with the C-terminal cysteine-rich
      domain block ligand binding of MARCO. The in vivo expression of this murine
      receptor is normally restricted to distinct populations of macrophages in the
      spleen and lymph nodes. During bacillus Calmette-Guerin (BCG) infection, during
      bacterial sepsis, or after the injection of purified LPS, however, the expression
      of MARCO is rapidly induced on macrophages in other tissues, including Kupffer
      cells in the liver. Using the mouse macrophage cell line J774.2, it was shown
      that LPS stimulation up-regulates surface expression of MARCO in a dose- and time
      dependent fashion. The proinflammatory cytokines IL-1, IL-6, TNF-alpha, and IFN
      gamma had little or no effect. Using inhibitory mAbs, the relevance of MARCO for
      the clearance of circulating bacteria in vivo was determined. Although the
      overall elimination of live Escherichia coli and Staphylococcus aureus from the
      blood did not appear to be affected by treatment with these Abs, the capturing of
      heat-killed bacteria by macrophages in the marginal zone areas of the spleen was
      clearly inhibited. This study suggests a role for MARCO in the host antibacterial
      defense.

PMID- 9916719
TI  - Identification of quantitative trait loci governing arthritis severity and
      humoral responses in the murine model of Lyme disease.
AB  - A spectrum of disease severity has been observed in patients with Lyme disease,
      with approximately 60% of untreated individuals developing arthritis. The murine
      model of Lyme disease has provided strong evidence that the genetic composition
      of the host influences the severity of arthritis following infection with
      Borrelia burgdorferi: infected C3H mice develop severe arthritis while infected
      C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling
      arthritis severity and humoral responses during B. burgdorferi infection were
      identified in the F2 intercross generation of C3H/HeNCr and C57BL/6NCr mice. Rear
      ankle swelling measurements identified quantitative trait loci (QTL) on
      chromosomes 4 and 5, while histopathological scoring identified QTL on a unique
      region of chromosome 5 and on chromosome 11. The identification of QTL unique for
      ankle swelling or histopathological severity suggests that processes under
      distinct genetic control are responsible for these two manifestations of Lyme
      arthritis. Additional QTL that control the levels of circulating Igs induced by
      B. burgdorferi infection were identified on chromosomes 6, 9, 11, 12, and 17.
      Interestingly, the magnitude of the humoral response was not correlated with the
      severity of arthritis in infected F2 mice. This work defines several genetic loci
      that regulate either the severity of arthritis or the magnitude of humoral
      responses to B. burgdorferi infection in mice, with implications toward
      understanding the host-pathogen interactions involved in disease development.

PMID- 9916720
TI  - Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide
      synthase in the replication of human cytomegalovirus in retinal pigment
      epithelial cells.
AB  - An in vitro model of human CMV infection of primary retinal pigment epithelial
      (RPE) cells was used to study the effects of cytokines on CMV replication in
      these cells, which are targets of CMV infection in vivo. IFN-gamma and IFN-beta
      were potent inhibitors of CMV replication in RPE cells, while TNF-alpha, IL
      1beta, or TGF-beta2 did not affect viral replication. Inhibition by IFN-gamma,
      and to a lesser extent IFN-beta, was almost completely reversed by addition of L
      tryptophan to the culture medium, strongly implicating the indoleamine 2,3
      dioxygenase (IDO) pathway. Polyadenylated IDO mRNA accumulation was detected as
      early as 2 h after IFN stimulation. Furthermore, CMV blocked the production of
      nitric oxide by the inducible form of nitric oxide synthase. This inhibition
      depended on a functional viral genome. However, exogenous nitric oxide
      significantly inhibited viral protein expression in RPE cells. Thus, CMV
      infection blocks the inducible nitric oxide synthase pathway activated by IFN
      gamma and IL-1beta, but cannot counteract the IFN-induced IDO pathway, which
      ultimately controls its replication in primary human RPE cells.

PMID- 9916721
TI  - IL-12 is not required for induction of type 1 cytokine responses in viral
      infections.
AB  - To investigate the physiological role of IL-12 in viral infections in terms of T
      cell cytokine responses involved in virus-specific Ig isotype induction and in
      antiviral protection, immune responses elicited upon infection of IL-12-deficient
      mice with lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus
      (VSV) were studied. Infection of IL-12-deficient mice with LCMV induced a virus
      specific type 1 cytokine response as determined by in vitro cytokine secretion
      patterns as well as by in vivo intracellular cytokine staining of LCMV-specific
      CD4+ TCR transgenic T cells that had clonally expanded in LCMV-infected IL-12
      deficient recipient mice. In addition, LCMV- and VSV-specific IgG responses
      exhibited normal serum IgG2a/IgG1 ratios, demonstrating again virus-specific CD4+
      T cell induction of type 1 phenotype in IL-12-deficient mice upon viral
      infection. LCMV and VSV immune mice were found to be protected against challenge
      immunization with recombinant vaccinia viruses expressing either the LCMV- or the
      VSV-derived glycoprotein, respectively. This protection is known to be mediated
      by T cell-secreted type 1 cytokines IFN-gamma and TNF-alpha. In contrast, IL-12
      deficient mice showed impaired abilities to control infection with the
      facultative intracellular bacterium Listeria monocytogenes at early time points
      after infection. However, at later time points of infection, IL-12-deficient mice
      were able to clear infection. These findings may indicate that viruses are able
      to induce type 1 T cell responses in the absence of IL-12 as opposed to some
      bacterial or parasitical infections that are crucially dependent on the presence
      of IL-12 for the induction of type 1 immune responses.

PMID- 9916722
TI  - Anti-TGF-beta treatment promotes rapid healing of Leishmania major infection in
      mice by enhancing in vivo nitric oxide production.
AB  - CB6F1 mice display intermediate susceptibility to Leishmania major infection
      compared with the highly susceptible BALB/c and resistant C57BL/6 parental
      strains. During early weeks of infection, these mice develop dominant Th2 type
      responses to L. major, although they eventually exhibit a Th2 to Th1 switch and
      spontaneously resolve their infections. In this study, we have examined the
      effects of either IL-12 or anti-TGF-beta therapy on the immune response and
      course of disease in chronically infected CB6F1 mice. Local treatment with IL-12
      inoculated into the parasitized lesion at 4 wk of infection induced a marked
      increase in IFN-gamma production but did not result in a significant reduction in
      numbers of parasite or promote more rapid healing. However, local treatment with
      an Ab to TGF-beta led to both a decrease in parasite numbers and more rapid
      healing, despite the fact that such treatment did not significantly alter the
      pattern of IL-4 and IFN-gamma production. Immunohistochemical studies showed that
      anti-TGF-beta treatment resulted in increased nitric oxide production within
      parasitized lesions. Our results suggest that TGF-beta may play an important
      regulatory role during chronic stages of a L. major infection by suppressing
      macrophage production of nitric oxide and that, in the absence of TGF-beta, even
      the relatively low levels of IFN-gamma observed in mice with dominant Th2-type
      responses are sufficient to activate macrophages to destroy amastigotes within
      parasitized lesions.

PMID- 9916723
TI  - Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity
      against Listeria monocytogenes.
AB  - CD8+ T cells require perforin to mediate immunity against some, but not all,
      intracellular pathogens. Previous studies with H-2b MHC perforin gene knockout
      (PO) mice revealed both perforin-dependent and perforin-independent pathways of
      CD8+ T cell-mediated immunity to Listeria monocytogenes (LM). In this study, we
      address two previously unresolved issues regarding the requirement for perforin
      in antilisterial immunity: 1) Is CD8+ T cell-mediated, perforin-independent
      immunity specific for a single Ag or generalizable to multiple Ags? 2) Is there a
      deficiency in the priming of the CD8+ T cell compartment of PO mice following an
      immunizing challenge with LM? We used H-2d MHC PO mice to generate CD8+ T cell
      lines individually specific for three known Ags expressed by a recombinant strain
      of virulent LM. Adoptive transfer experiments into BALB/c host mice revealed that
      immunity can be mediated by PO CD8+ T cells specific for all Ags examined,
      indicating that perforin-independent immunity is not limited to CD8+ T cells that
      recognize listeriolysin O. Analysis of epitope-specific CD8+ T cell expansion by
      MHC class I tetramer staining and ELISPOT revealed no deficiency in either the
      primary or secondary response to LM infection in PO mice. These results
      demonstrate that the perforin-independent pathway of antilisterial resistance
      mediated by CD8+ T cells is generalizable to multiple epitopes. Furthermore, the
      results show that reduced antilisterial resistance observed with polyclonal PO
      CD8+ T cells is a consequence of a deficiency in effector function and not a
      result of suboptimal CD8+ T cell priming.

PMID- 9916724
TI  - High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo
      antitumor efficacy.
AB  - A majority of the human tumor-associated Ags characterized to date are derived
      from nonmutated "self"-proteins. Little is currently understood about the nature
      of the self-reactive lymphocytes that recognize these Ags. We recently
      characterized two nonmutated tumor-associated Ags for the B16 murine melanoma:
      tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope
      protein, p15E. We previously reported that both TRP-2 and p15E reactive CTL could
      be detected in the spleens of naive animals after a single in vitro stimulation
      using 10(-5)-10(-6) M of the appropriate Kb-binding 9-amino acid epitope. In this
      report we show that the CTL found in naive animals are low avidity lymphocytes,
      that respond only to high concentrations of peptide in vitro. We demonstrate that
      titration of in vitro-stimulating peptide to limiting concentrations
      distinguishes qualitative differences in the lymphocyte reactivity to these two
      Ags between vaccinated and unvaccinated animals. We further demonstrate that in
      vitro expansion of CTL in either high or low concentrations of stimulating
      peptide generated CTL cultures with different avidities for the relevant
      epitopes. CTL expanded in low concentrations demonstrated higher avidity for
      peptide-pulsed targets and better tumor recognition, when compared to CTL
      generated in the presence of high concentrations of Ag. More importantly, high
      avidity CTL demonstrated superior in vivo antitumor activity. These results
      demonstrate that qualitative differences in the CTL that recognize these two self
      Ags are critically important to their in vitro and in vivo anti-tumor efficacy.

PMID- 9916725
TI  - Development of an animal model for neurocysticercosis: immune response in the
      central nervous system is characterized by a predominance of gamma delta T cells.
AB  - Neurocysticercosis is the most common parasitic disease of the central nervous
      system worldwide. It is caused by the metacestode form of the helminth Taenia
      solium. Study of the immune response in the human brain has been limited by the
      chronic progression of the disease, the influence of corticosteroid treatment,
      and the scarcity of patients who undergo surgical intervention. To better
      understand the immune response and associated pathology in neurocysticercosis, a
      mouse model was developed by intracranial infection of BALB/c mice with
      Mesocestoides corti, a cestode organism related to T. solium. The immune response
      reveals the presence of abundant inflammatory infiltrates appearing as early as 2
      days postinfection in extraparenchymal regions. In contrast, infiltration of
      immune cells into parenchymal tissue is significantly delayed. There is a natural
      progression of innate (neutrophils and macrophages), early induced (NK cells and
      gamma delta T cells), and adaptive immune responses (alpha beta T cells and B
      cells) in infected mice. Gamma delta T cells are the predominant T cell
      population. A cell-mediated Th1 pathway of cytokine expression is evident in
      contrast to the previously described Th2 phenotype induced in the periphery.

PMID- 9916726
TI  - Activated eosinophils are the major source of Th2-associated cytokines in the
      schistosome granuloma.
AB  - Eosinophils are a numerically dominant cell population within the schistosome
      granuloma. These granuloma eosinophils can produce a variety of cytokines,
      including IL-2, IL-4, IL-5, and IFN-gamma. Therefore, eosinophils may play a key
      role in the determination of the unique cytokine microenvironment within the
      granuloma milieu. These studies investigated the potential role of eosinophils in
      the regulation of granuloma immunopathology. We have characterized spleen- and
      granuloma-derived eosinophils based on cellular activation and cytokine
      production during the development of murine schistosomiasis. Based on the
      criteria of hypodensity and CD69 expression, granuloma eosinophils were highly
      activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils
      were also activated at 7 wk postinfection, but were much more heterogeneous than
      their granuloma counterparts. By 11 wk postinfection, few hypodense splenic
      eosinophils were observed. Eosinophils represented the majority of cytokine
      producing cells in the granuloma and were a dominant source of IL-4. Eosinophils
      also produced IL-2, IL-5, and IFN-gamma, using the criteria of mRNA in situ
      hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil
      activation and cytokine production were greatest at the time of maximum granuloma
      formation, i.e., 10-12 wk after initial cercarial exposure. Therefore, locally
      activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines
      in the granuloma milieu and may be important determinators of immunopathology in
      schistosomiasis.

PMID- 9916727
TI  - IL-10 gene knockout mice show enhanced Th1-like protective immunity and absent
      granuloma formation following Chlamydia trachomatis lung infection.
AB  - We previously reported that higher IL-10 production is correlated with lower IFN
      gamma production, weaker delayed hypersensitivity (DTH), and slower organism
      clearance following chlamydial infection in mice. To assess more directly the
      role of IL-10, we examined protective immunity and pathological reaction in
      C57BL/6 IL-10 gene knockout (KO) and wild-type mice. The results showed that in
      the absence of endogenous IL-10, mice had significantly accelerated chlamydial
      clearance and developed significantly stronger DTH responses, which could be
      inhibited by local delivery of rIL-10. Consistent with the enhancement of DTH
      responses, IL-10 KO mice showed stronger and more persistent CD4 T cell-dependent
      IFN-gamma production and significant elevation of IL-12 and TNF-alpha production.
      Additionally, wild-type, but not IL-10 KO, mice showed granuloma formation that
      was correlated with higher levels of Th2 cytokine (IL-5) production at the later
      stages of infection. Moreover, chlamydial infection, unlike parasitic protozoan
      infection, did not induce significant acute toxicity in IL-10 KO mice, which may
      be due to the low (undetectable) levels of systemic release of proinflammatory
      cytokines. These results suggest that IL-10 inhibits the priming and expansion of
      Th1-like T cell responses and that IL-10 plays a role in the fibrotic reaction
      seen with chlamydial infection.

PMID- 9916728
TI  - Mice lacking mature T and B lymphocytes develop arthritic lesions after
      immunization with type II collagen.
AB  - Collagen-induced arthritis in DBA/1 mice is a widely used experimental model of
      rheumatoid arthritis. The induction phase of the disease is thought to be
      dependent upon MHC-restricted T and B cell-mediated immune responses to type II
      collagen, but an influence of additional non-MHC-restricted mechanisms has also
      been proposed. In this study, we report that type II collagen immunization of
      DBA/1 mice lacking mature T and B lymphocytes resulted in the development of
      arthritic lesions, which were characterized by synovial hyperplasia with
      occasional inflammation as well as cartilage and bone destruction. The
      specificity of disease induction to type II collagen was confirmed, because
      arthritis could not be induced when control preparations of OVA or adjuvant alone
      were administered. A delay in clinical disease onset and a reduction in severity
      between lymphocyte-positive and -negative DBA/1 mice confirmed that lymphocytes
      play an important role in disease; however, similar pathologic features and
      normal incidence suggest that lymphocyte-independent mechanisms of disease
      induction also operate in the standard collagen-induced arthritis model. We
      conclude that adaptive immune responses are not the only arthritogenic mechanism
      and hypothesize that the nonantigenic properties of type II collagen can also
      lead to arthritis.

PMID- 9916729
TI  - Osteopontin is associated with T cells in sarcoid granulomas and has T cell
      adhesive and cytokine-like properties in vitro.
AB  - Sarcoidosis is a systemic disease characterized by the accumulation of activated
      T cells and widespread granuloma formation. In addition, individual genetic
      predisposition appears to be important in this disease. Osteopontin, a
      noncollagenous matrix protein produced by macrophages and T lymphocytes, is
      expressed in the granulomas of tuberculosis, and is associated with genetic
      susceptibility to intracellular infection. The function of osteopontin in these T
      cell-mediated responses is unknown. We sought to elucidate the role of
      osteopontin in granulomatous inflammation by characterizing its expression in
      different stages of sarcoidosis and its effector function on T cells in vitro.
      Lymphocyte-associated expression of osteopontin in sarcoidosis was demonstrated
      by immunohistochemistry, and its expression correlated with granuloma maturity.
      In addition, osteopontin induced T cell chemotaxis, supported T cell adhesion (an
      effect enhanced by thrombin cleavage of osteopontin), and costimulated T cell
      proliferation. These results suggest a novel mechanism by which osteopontin and
      thrombin modulate T cell recruitment and activation in granulomatous
      inflammation.

PMID- 9916730
TI  - The mast cell as site of tissue-type plasminogen activator expression and
      fibrinolysis.
AB  - Recent data suggest that mast cells (MC) and their products (heparin, proteases)
      are involved in the regulation of coagulation and fibrino(geno)lysis. The key
      enzyme of fibrinolysis, plasmin, derives from its inactive progenitor,
      plasminogen, through catalytic action of plasminogen activators (PAs). In most
      cell systems, however, PAs are neutralized by plasminogen activator inhibitors
      (PAIs). We report that human tissue MC as well as the MC line HMC-1
      constitutively produce, express, and release tissue-type plasminogen activator
      (tPA) without producing inhibitory PAIs. As assessed by Northern blotting, highly
      enriched lung MC (>98% pure) as well as HMC-1 expressed tPA mRNA, but did not
      express mRNA for PAI-1, PAI-2, or PAI-3. The tPA protein was detectable in MC
      conditioned medium by Western blotting and immunoassay, and the MC agonist stem
      cell factor (c-Kit ligand) was found to promote the release of tPA from MC. In
      addition, MC-conditioned medium induced fibrin-independent plasmin generation as
      well as clot lysis in vitro. These observations raise the possibility that MC
      play an important role in endogenous fibrinolysis.

PMID- 9916731
TI  - TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the
      principal subcellular location of TNF-R1.
AB  - The subcellular localization of TNF-R1 to the Golgi apparatus, initially observed
      in endothelial cells, has been confirmed using transfection of bovine aortic
      endothelial cells with a human TNF-R1 expression plasmid. The subcellular
      interactions of TNF-R1 and the TRADD (TNFR-associated death domain protein)
      adaptor protein have been analyzed in the human monocyte cell line U937 and the
      human endothelial cell line ECV304 by confocal immunofluorescence microscopy and
      by Western blot analysis of fractionated cell extracts. In untreated cells, in
      which TNF-R1 is found on the cell surface but principally localizes to the trans
      Golgi network, TRADD is concentrated in the cis- or medial-Golgi region, but
      separates from the Golgi during cell fractionation. Coimmunoprecipitation studies
      have shown that TRADD binds to TNF-R1 within 1 min of TNF treatment in a cell
      fraction-containing plasma membrane. This association is followed by a gradual
      dissociation, which is prevented if receptor-mediated endocytosis is inhibited by
      hypertonic medium. In contrast, no association is detected between TRADD and TNF
      R1 in the Golgi in response to exogenous TNF at any time examined. These results
      suggest that although TNF-R1 is predominantly a Golgi-associated protein and
      TRADD also localizes to the Golgi region, exogenous TNF causes TRADD to bind to
      TNF-R1 only at the plasma membrane.

PMID- 9916732
TI  - Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium
      acnes-primed IFN-gamma-deficient mice by a concomitant reduction of TNF-alpha, IL
      12, and IL-18 production.
AB  - The present study was designed to investigate the role of IFN-gamma in LPS
      induced liver injury following priming with Propionibacterium acnes. At 1 week
      after priming BALB/c mice with P. acnes, a large number of macrophages (Mphi) and
      lymphocytes predominantly infiltrated the portal area, resulting in the
      intrahepatic formation of granulomas consisting of epithelioid and lymphoid
      cells. In comparison, in IFN-gamma gene-disrupted BALB/c mice (IFN-gamma knockout
      mice), the number of infiltrated Mphi was decreased, with a significant reduction
      in the number and size of granulomas. Subsequent elicitation with a low dose of
      LPS induced massive hepatic necrosis in wild-type BALB/c mice, with a marked
      increase in the serum levels of TNF-alpha, IL-12, and IL-18 and subsequently of
      alanine transferase. In contrast, IFN-gamma knockout mice developed scattered
      focal necrosis of the liver with significantly lower levels of serum alanine
      transferase as well as drastic decreases in TNF-alpha, IL-12, and IL-18
      production. The administration of an anti-IFN-gamma neutralizing mAb at the
      eliciting phase significantly alleviated liver injury and reduced serum IL-12 and
      IL-18 levels. Thus, endogenously produced IFN-gamma is involved in the
      pathogenesis of this liver injury model by regulating Mphi infiltration and
      granuloma formation in the priming phase as well as cytokine production in the
      eliciting phase.

PMID- 9916733
TI  - IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3
      in NC/Nga mice, a model for human atopic dermatitis.
AB  - IgE hyperproduction frequently observed in patients with atopic dermatitis (AD)
      may greatly contribute to the pathogenesis of AD, but its mechanisms are still
      unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered
      from AD-like skin lesions with elevation of plasma IgE levels. We investigated
      mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF
      NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of
      BALB/c mice. Although there was no difference in the expression of CD40 on B
      cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more
      IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or
      IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells,
      which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells
      isolated from PBMC of AD patients with high serum IgE levels, JAK3 was
      constitutively phosphorylated at the tyrosine residue, and its phosphorylation
      was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B
      cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested
      that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive
      to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and
      patients with AD.

PMID- 9916735
TI  - Regulation of acute lung inflammatory injury by endogenous IL-13.
AB  - Using IgG immune complex deposition to trigger acute lung inflammation in rats,
      we have previously shown that exogenously administered IL-13 suppresses the acute
      inflammatory response. In the same model, expression of both mRNA and protein for
      IL-13 has now been detected. Treatment of rats with Ab to IL-13 accentuated the
      inflammatory response, with significant increases in lung vascular permeability
      and in the number of neutrophils in bronchoalveolar lavage fluids. In the
      presence of anti-IL-13, activation of the transcription factor, NF-kappaB, was
      significantly increased in lung. In addition, anti-IL-13 caused significant
      increases in bronchoalveolar lavage levels of TNF-alpha, macrophage inflammatory
      protein-2, and cytokine-inducible neutrophil chemoattractant but no changes in
      lung vascular ICAM-1. These data suggest that during lung inflammation endogenous
      IL-13 regulates NF-kappaB activation and related cytokine/chemokine generation,
      all of which determines the intensity of the lung inflammatory response.

PMID- 9916734
TI  - IL-12 is a heparin-binding cytokine.
AB  - Using an ELISA approach, we demonstrate that recombinant human IL-12 (rhIL-12)
      binds strongly to an immobilized heparin-BSA complex. This binding is completely
      displaceable with soluble heparin, IC50 approximately 0.1 microg/ml,
      corresponding to approximately 10 nM. By interpolation with our previous
      findings, this indicates an affinity for heparin greater than that of
      antithrombin III and comparable with that of FGF-2, two high-affinity heparin
      binding proteins. Recombinant murine IL-12 also binds strongly to heparin. The
      binding of rhIL-12 to heparin shows specificity because chondroitin sulfates A
      and C fail to compete, whereas chondroitin B inhibits weakly. A highly sulfated
      heparan sulfate is a strong competitor, whereas other heparan sulfates show weak
      or no activity. Small heparin fragments inhibit binding, although activity
      decreases with size. An octasaccharide pool derived by cleavage of heparin with
      nitrous acid is a significantly stronger inhibitor than its heparinase I-derived
      counterpart, further indicating structural specificity in the interaction between
      rhIL-12 and heparin. The binding of recombinant p40 to heparin appears
      indistinguishable from that of the IL-12 heterodimer, implying that the heparin
      binding site is largely if not solely located in this subunit. These results show
      for the first time that IL-12 is a heparin-binding cytokine, a property common to
      the other Th1-response-inducing cytokines, IFN-gamma and IL-2. Our findings
      strongly suggest that IL-12 will tend to be retained close to its sites of
      secretion in the tissues by binding to heparin-like glycosaminoglycans, thus
      favoring a paracrine role for IL-12.

PMID- 9916736
TI  - Chemotactic migration triggers IL-8 generation in neutrophilic leukocytes.
AB  - Neutrophils recovered from inflammatory exudates possess increased levels of IL
      8, but exposure of neutrophils to chemoattractants results in only a modest
      stimulation of IL-8 generation. This study was undertaken to explore the
      hypothesis that IL-8 generation in these cells is dependent upon the process of
      migration. Neutrophils synthesized up to 30 times as much IL-8 during migration
      in response to a gradient of diverse chemoattractants than they did when
      stimulated directly by the attractants in the absence of a gradient. This IL-8
      response was dependent on migration since it was not observed in cells exposed to
      concentration gradients of chemoattractants under conditions that prevented cell
      movement. While actinomycin-D (1 microg/ml) had little influence on the
      generation of IL-8 during chemotaxis, the protein synthesis inhibitor
      cycloheximide (10 microg/ml) markedly blunted the accumulation of cell-associated
      IL-8, suggesting that new protein synthesis from preexisting mRNA was responsible
      for the effect. Consistent with this interpretation, migrating cells incorporated
      over 10 times as much [3H]leucine into IL-8 as did nonmotile neutrophils exposed
      to chemoattractants. A substantial portion of the IL-8 generated during
      chemotaxis was released upon subsequent metabolic stimulation. Thus, the IL-8
      synthesized during chemotaxis is uniquely positioned to exert a regulatory
      influence on inflammatory processes governed by neutrophilic leukocytes
      responding to inflammatory and infectious stimuli.

PMID- 9916737
TI  - High affinity very late antigen-4 subsets expressed on T cells are mandatory for
      spontaneous adhesion strengthening but not for rolling on VCAM-1 in shear flow.
AB  - The very late Ag-4 (VLA-4) integrin supports both rolling and firm adhesion of
      leukocytes on VCAM-1 under shear flow. The molecular basis for the unique ability
      of a single adhesion molecule to mediate these versatile adhesive processes was
      investigated. VLA-4 occurs in multiple activation states, with different
      affinities to ligand. In this study we tested how these states regulate VLA-4
      adhesiveness under shear flow in Jurkat T cells and PBL. VLA-4 on nonstimulated
      Jurkat cells supported rolling and spontaneous arrest on VCAM-1, whereas a Jurkat
      activation mutant with reduced VLA-4 affinity failed to spontaneously arrest
      after tethering to or during rolling on VCAM-1. The contribution of VLA-4
      affinity for ligand to rolling and spontaneous arrests on immobilized VCAM-1 was
      dissected using soluble VLA-4 ligands, which selectively block high affinity
      states. VLA-4 saturation with ligand completely blocked spontaneous adhesion
      strengthening post-tethering to VCAM-1, but did not impair rolling on the
      endothelial ligand. High affinity VLA-4 was found to comprise a small subset of
      VLA-4 on resting Jurkat cells and PBL. This subset is essential for firm adhesion
      but not for tethering or rolling adhesions on VCAM-1. Interestingly, low and high
      affinity VLA-4 states were found to mediate similar initial tethering to ligand.
      High affinity VLA-4, constitutively expressed on circulating T cells, may control
      their early adhesion strengthening on VCAM-1-expressing endothelium before
      exposure to vascular chemokines and activation of additional integrins.

PMID- 9916738
TI  - IL-18 is produced by articular chondrocytes and induces proinflammatory and
      catabolic responses.
AB  - IL-18, a cytokine originally identified as IFN-gamma-inducing factor, is a member
      of the IL-1 family of proteins. Because IL-1alpha and IL-1beta are important
      mediators in the pathogenesis of arthritis, the present study addresses the
      expression of IL-18 and its role in regulating in articular chondrocytes. IL-18
      mRNA was induced by IL-1beta in chondrocytes. Chondrocytes produced the IL-18
      precursor and in response to IL-1 stimulation secreted the mature form of IL-18.
      Studies on IL-18 effects on chondrocytes showed that it inhibits TGF-beta-induced
      proliferation and enhances nitric oxide production. IL-18 stimulated the
      expression of several genes in normal human articular chondrocytes including
      inducible nitric oxide synthase, inducible cyclooxygenase, IL-6, and stromelysin.
      Gene expression was associated with the synthesis of the corresponding proteins.
      Treatment of normal human articular cartilage with IL-18 increased the release of
      glycosaminoglycans. These finding identify IL-18 as a cytokine that regulates
      chondrocyte responses and contributes to cartilage degradation.

PMID- 9916739
TI  - TGF-beta increases leukotriene C4 synthase expression in the monocyte-like cell
      line, THP-1.
AB  - The goal of this study was to determine whether cytokines modulate leukotriene C4
      (LTC4) synthase expression in mononuclear phagocytes. A panel of cytokines was
      surveyed for changes in LTC4 synthase mRNA in THP-1 cells. TGF-beta1, -2, and -3
      had significant stimulatory effects. The addition of TGF-beta resulted in a time
      dependent increase in LTC4 synthase mRNA at 6 h, which persisted through 48 h.
      Furthermore, this conditioning resulted in an increase in immunoreactive protein
      for LTC4 synthase through 7 days. TGF-beta conditioning of cells resulted in a
      time- and dose-dependent increase in stimulated LTC4 synthase activity. Following
      transient transfection of THP-1 cells with a promoter-reporter construct
      containing 1.2 kb of the LTC4 synthase promoter, TGF-beta treatment resulted in a
      2-fold increase in reporter activity. Conditioning with TGF-beta did not prolong
      the half-life of LTC4 synthase mRNA, as assessed by RNase protection assays in
      actinomycin D-treated cells. Cycloheximide exposure experiments revealed that new
      protein synthesis was not required for the observed stimulatory effect of TGF
      beta on LTC4 synthase mRNA. We conclude that LTC4 synthase expression is
      increased at a transcriptional level by TGF-beta in mononuclear phagocytes.

PMID- 9916740
TI  - One active C1r subunit is sufficient for the activity of the complement C1
      complex: stabilization of C1r in the zymogen form by point mutations.
AB  - The binding of C1 (the first component of complement) to immune complexes leads
      to the autoactivation of C1r through the cleavage of the Arg463-Ile464 bond in
      the catalytic domain. Spontaneous activation of C1r (and C1) also occurs in the
      fluid phase, preventing the characterization of the zymogen form of C1r. To
      overcome this difficulty, the zymogen form of human C1r was stabilized by
      mutating the Arg in the Arg463-Ile464 bond to Gln. This mutant was designated as
      mutant QI. Recombinant C1r (wild type (wt) or mutant) was expressed in insect
      cells using serum-free medium in functionally pure form; therefore, the cell
      culture supernatant was suitable to reconstruct C1 for the hemolytic assay.
      Mutant QI was a stable, nonactivable zymogen and showed no hemolytic activity in
      reconstituted C1. However, this stable zymogen C1r mutant could form an active
      mixed dimer with the wt C1r, indicating that one active C1r subunit in the C1
      complex is sufficient for the full activity of the entire complex. Our
      experiments also showed that the exchange of C1r monomers between the C1r dimers
      is completed in less than 16 h even at pH 7 and 4 degrees C. Two other mutants
      were also constructed by changing Arg463 to Lys, or Ile464 to Phe, and were
      designated as mutants KI and RF, respectively. Although these substitutions did
      increase the stability of the proenzyme in the cell culture supernatant, the
      mutant proteins retained their ability to autoactivate, and both had a wt-like
      hemolytic activity.

PMID- 9916741
TI  - Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding
      putative phosphate transport receptors.
AB  - Using culture filtrate Ag-specific mAbs generated from mycobacteria-infected H-2b
      haplotype mice, we have previously identified three genes in the Mycobacterium
      tuberculosis genome, encoding proteins homologous to the periplasmic ATP-binding
      cassette phosphate-binding receptor PstS of the phosphate-specific transport
      system of E. coli. To define the potential vaccinal properties of these phosphate
      binding proteins, female C57BL/6 mice were injected i.m. with plasmid DNA
      encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and
      immunogenicity and protective efficacy against i.v. challenge with M.
      tuberculosis H37Rv was analyzed. Significant levels of highly Ag-specific Abs and
      Th1-type cytokines IL-2 and IFN-gamma could be detected following vaccination
      with each of the three genes. However, only mice vaccinated with PstS-3 DNA
      demonstrated significant and sustained reduction in bacterial CFU numbers in
      spleen and lungs for 3 mo after M. tuberculosis challenge, as compared with CFU
      counts in mice vaccinated with control DNA. Vaccination with PstS-2 DNA induced a
      modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1
      DNA was completely ineffective in reducing bacterial multiplication. In
      conclusion, our results indicate that DNA vaccination is a powerful and easy
      method for comparative screening of potentially protective Ags from M.
      tuberculosis and that the PstS-3 protein is a promising new subunit vaccine
      candidate.

PMID- 9916742
TI  - Adhesion-dependent degranulation of neutrophils requires the Src family kinases
      Fgr and Hck.
AB  - Polymorphonuclear neutrophils (PMN) adherent to integrin ligands respond to
      inflammatory mediators by reorganizing their cytoskeleton and releasing reactive
      oxygen intermediates. As Src family tyrosine kinases are implicated in these
      responses, we investigated their possible role in regulating degranulation. Human
      PMN incubated on fibrinogen released lactoferrin in response to TNF-alpha and
      this response was inhibited by PP1, a Src family tyrosine kinase inhibitor. This
      drug had no effect on lactoferrin secretion induced by PMA, an adhesion
      independent agonist of PMN degranulation. However, PP1 blocked secretion in PMN
      plated on plain tissue culture plastic, a surface inducing PMN spreading in the
      absence of any stimulus. Double knockout hck-/- fgr-/- PMN adherent to collagen
      or fibrinogen failed to release lactoferrin in response to TNF-alpha but
      responded to PMA as wild-type PMN. Degranulation induced by spreading over tissue
      culture plastic was also defective in hck-/- fgr-/- PMN. Defective adhesion
      dependent degranulation required the absence of both kinases, because single
      knockout fgr-/- or hck-/- PMN responded as wild-type cells. Analysis of
      lactoferrin secretion in hck-/- fgr-/- or PP1-treated, suspended PMN showed that
      Src kinases are not implicated in degranulation dependent on activation of
      protein kinase C or increase in intracellular free Ca2+ but may play a role in
      the response to FMLP of cytochalasin B-treated PMN. These findings identify a
      role for Src family kinases in a signaling pathway leading to granule-plasma
      membrane fusion and suggest that Fgr and Hck would be targets for pharmacological
      control of adhesion-dependent degranulation in the inflammatory site.

PMID- 9916743
TI  - A comparison of C3a and C5a-mediated stable adhesion of rolling eosinophils in
      postcapillary venules and transendothelial migration in vitro and in vivo.
AB  - The comparative ability of the complement anaphylatoxins C3a and C5a to mediate
      leukocyte adhesion and transendothelial migration in vivo and in vitro was
      investigated. Superfusion of IL-1beta-stimulated rabbit mesentery with C3a
      resulted in a rapid and stable adhesion of rolling eosinophils, but not
      neutrophils, to postcapillary venules. However, C3a failed to evoke subsequent
      transmigration of the adherent eosinophils. In contrast, C5a induced both the
      rapid activation-dependent firm adhesion and transmigration of eosinophils and
      neutrophils through venular endothelium. C3a induced selective shedding of L
      selectin and an increase in alphaMbeta2 integrin expression on eosinophils but
      not neutrophils, while C5a induced shedding of L-selectin and up-regulation of
      alphaMbeta2 integrin on both eosinophils and neutrophils. Both C3a- and C5a
      dependent adhesion to venular endothelium was blocked by ex vivo treatment of
      eosinophils with anti-alpha4 and anti-beta2 integrin mAbs. In vitro, both C3a
      (but not C3a(desArg)) and C5a (including C5a(desArg))-dependent transmigration of
      eosinophils across IL-1beta-stimulated endothelial monolayer was mediated by
      alpha4beta1 and alphaMbeta2 integrins. Overall these studies suggest that C3a is
      eosinophil-specific chemotactic mediator that influences selectively eosinophil
      adhesion but not transmigration in vivo. C5a in contrast is a complete activator
      of integrin-dependent adhesion as well as transmigration of eosinophils and
      neutrophils.

PMID- 9916744
TI  - Varying roles of E-selectin and P-selectin in different microvascular beds in
      response to antigen.
AB  - Expression of E-selectin and P-selectin is critical in the effector phase of
      leukocyte recruitment in response to Ag. Whether their relative roles differ
      between tissues in response to the same Ag is unknown. In this study, a type I
      hypersensitivity response was elicited in C57BL/6 mice by systemic sensitization
      with OVA. Following local Ag challenge, endothelial selectin expression was
      examined in the skin and cremaster muscle microvasculature using a dual
      radiolabeled mAb technique. Next, the dermal and muscle microcirculations were
      visualized using intravital microscopy to establish roles for P-selectin and/or E
      selectin. In untreated mice, leukocyte recruitment in both skin and skeletal
      muscle was mediated entirely by P-selectin. Following Ag challenge, leukocyte
      rolling flux and adhesion were dramatically increased and leukocyte rolling
      velocity was unchanged in muscle. Only P-selectin expression increased in muscle,
      and leukocyte recruitment was entirely dependent upon this selectin. In contrast,
      in Ag-challenged skin, leukocyte rolling flux did not increase, but rolling
      velocity dropped profoundly. In skin, only E-selectin expression increased, and
      blockade of either E-selectin or P-selectin had minimal effect on either rolling
      flux or rolling velocity. Blockade of both selectins reduced rolling flux by 80%
      and increased rolling velocity sevenfold. These data highlight striking
      differences in expression of the endothelial selectins in separate microvascular
      beds in response to the same stimulus and demonstrate that these differences
      underlie very different patterns of leukocyte recruitment. The data underscore
      the importance of studying individual microvascular beds to understand tissue
      specific leukocyte recruitment in vivo.

PMID- 9916745
TI  - Inhibition of experimental autoimmune encephalomyelitis by a tyrosine kinase
      inhibitor.
AB  - Migration of lymphocytes from the blood into the brain is a critical event in the
      pathogenesis of experimental autoimmune encephalomyelitis. Lymphocyte adhesion to
      brain endothelium is the first step in lymphocyte entry into the central nervous
      system, leading subsequently to myelin damage and paralysis. In this paper we
      show that the tyrosine kinase inhibitor, tyrphostin AG490, prevents binding of
      freshly isolated mouse lymph node cells and of in vivo activated lymphocytes to
      endothelium of inflamed brain in Stamper-Woodruff adhesion assays. Moreover,
      AG490 inhibits adhesion of encephalitogenic T cell lines to purified ICAM-1 and
      VCAM-1, molecules implicated in T cell recruitment into the central nervous
      system. In contrast, 2-h treatment of T cell lines with high doses of tyrphostin
      AG490 have no effect on the viability, intracellular calcium elevation induced by
      Con A or TCR cross-linking, proliferation, or TNF production by Ag-stimulated T
      cell lines. Systemic administration of AG490 prevents the accumulation of
      leukocytes in the brain and the development of experimental autoimmune
      encephalomyelitis induced by proteolipid protein, peptide 139-151-specific T cell
      lines in SJL/J mice. Blood leukocytes isolated from mice treated with tyrphostin
      AG490 are less adhesive on purified very late Ag-4 ligands compared with adhesion
      of leukocytes from control animals. Our results suggest that inhibition of
      signaling pathways involved in lymphocyte adhesion may represent a novel
      therapeutic approach for demyelinating diseases.

PMID- 9916746
TI  - Involvement of MIIC-like late endosomes in B cell receptor-mediated antigen
      processing in murine B cells.
AB  - Currently, the involvement of classical vs novel endocytic compartments in the
      phenomenon of B cell receptor (BCR)-mediated Ag processing is a matter of
      considerable debate. In murine B cells, class II vesicles (CIIV) represent a
      novel endocytic compartment involved in BCR-mediated Ag processing and class II
      peptide loading. Alternatively, in human B cells, the MHC class II-enriched
      compartment (MIIC) represents a lysosome (L)-like endocytic compartment that
      appears to be involved in this process. Presently, the relationship between CIIV,
      MIIC, and classical endosomes and L remains to be determined. Using density
      gradient centrifugation, a subcellular compartment morphologically and
      immunologically similar to human MIIC has been identified, isolated, and
      characterized in murine B cells. These MIIC-like vesicles represent a population
      of class II-positive late endosomes (LE) and are distinct from CIIV. MIIC-like LE
      are uniquely marked by the thiol protease cathepsin B, and along with mature L,
      appear to be the major repository of DM molecules in these cells. Importantly,
      both MIIC-like LE and CIIV isolated from Ag-pulsed B cells contain BCR
      internalized Ag as well as antigenic peptide-class II complexes.

PMID- 9916747
TI  - Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in
      patients with acute and chronic hepatitis C.
AB  - The inverse relationship between peripheral blood CTL responsiveness to multiple
      hepatitis C virus (HCV) epitopes and viral titer in patients with persistent HCV
      infection suggests that enhancement of the CTL response might result in viral
      clearance. Since several HLA-A2-restricted HCV CTL epitopes are already known, we
      aimed to identify CTL epitopes restricted by other HLA types in an effort to
      expand the epitope repertoire available for T cell-mediated therapeutic vaccine
      development. Scanning of 14 different HCV genome sequences for the presence of
      conserved peptides containing the HLA-A3 and -B7 motifs revealed 9- to 10-mer
      peptides that were synthesized and assayed for binding to HLA-A3, -B7 supertype
      molecules. Peptides with good HLA-binding affinities and cross-reactivities with
      at least three of five most common molecules of each supertype were tested for
      the ability to stimulate a memory CTL response in the peripheral blood from
      selected HCV-infected patients and normal seronegative donors in vitro. We
      identified eight HLA-A3 supertype-restricted CTL epitopes and one HLA-B7
      supertype-restricted CTL epitope that were recognized by infected patients but
      not by healthy seronegative donors. HLA class I serotyping of 158 chronically
      infected patients revealed that 80% expressed one or more of HLA molecules belong
      to either the A2, A3, or B7 supertypes. In conclusion, the epitopes, herein
      identified combined with previously defined HLA-A2-restricted CTL epitopes,
      should be useful for the design of an ethnically unbiased, therapeutic CTL
      vaccine for the treatment of patients with chronic HCV infection.

PMID- 9916749
TI  - Antigen-dependent and -independent IFN-gamma modulation by penicillins.
AB  - The activation of CD4+ T lymphocytes upon Ag stimulation plays a critical role in
      adverse immune responses including drug-specific hypersensitivity reactions. We
      examined the modulation of T cell phenotype induced by hapten-specific
      stimulation using the model of beta-lactam antibiotics such as penicillin G (Pen
      G), Pen V, and ampicillin (Amp). When PBMC of donors suffering from
      hypersensitivity reactions against beta-lactams were stimulated in vitro with
      different doses of Pen G, a preferential expansion of IL-4-producing TCR
      alphabeta+ cells was detected. A panel of T cell clones was then prepared from
      Pen G-specific lines after two cycles of restimulation with the hapten. For the
      majority of these clones, we found that high doses of Pen G induced optimal IL-4
      secretion, whereas the amount of IFN-gamma secreted was inversely correlated with
      the dose of Pen G, thus leading to a hapten-inducible shift of the functional
      phenotypes for some of the clones. Finally, Pen V and Amp were used to modulate
      different Ag-induced immune responses. We found that Amp had no influence on the
      cytokine pattern induced by specific Ag or mitogens. In contrast, Pen V inhibited
      the secretion of IFN-gamma, but not IL-4, most likely by Ag-independent
      mechanisms. This last finding may open new applications for immune intervention
      in those diseases in which polarized Th1 responses are involved in the
      development of the pathology.

PMID- 9916748
TI  - IFN-gamma induces endothelial cells to proliferate and to invade the
      extracellular matrix in response to the HIV-1 Tat protein: implications for AIDS
      Kaposi's sarcoma pathogenesis.
AB  - Previous studies indicated that the Tat protein of HIV functions as a progression
      factor in Kaposi's sarcoma (KS), an angioproliferative disease common and
      aggressive in HIV-1-infected individuals (AIDS-KS). In particular, Tat that is
      released by infected cells stimulates the growth and invasion of spindle cells of
      endothelial origin derived from KS lesions (KS cells). Other work suggested that
      inflammatory cytokines may act as initiating factors in KS since they induce
      normal endothelial cells to acquire the same phenotype and functional features of
      KS cells, including the responsiveness to Tat. In this study, we show that among
      the inflammatory cytokines increased in AIDS-KS lesions, IFN-gamma alone is
      sufficient to induce endothelial cells to proliferate and to invade the
      extracellular matrix in response to Tat. This is because IFN-gamma up-regulates
      the expression and activity of the receptors for Tat identified as the integrins
      alpha5beta1 and alpha(v)beta3. These results suggest that, by triggering Tat
      effects, IFN-gamma plays a major role in AIDS-KS pathogenesis.

PMID- 9916750
TI  - Increased activation of protein kinase A type I contributes to the T cell
      deficiency in common variable immunodeficiency.
AB  - The molecular mechanisms underlying the T cell dysfunction often present in
      common variable immunodeficiency (CVI) are not established. cAMP-dependent
      protein kinase A type I (PKAI) is an important inhibitor of T cell proliferation
      after Ag stimulation. We therefore investigated the possibility that activation
      of PKAI may be involved in the development of T cell dysfunction in CVI. An
      exogenously added PKAI-selective antagonist (Rp-8-Br-cAMPS) induced a significant
      increase in anti-CD3-stimulated PBMC proliferation in 20 CVI patients compared
      with no effect in 15 controls. Purified T cells from 7 CVI patients with strictly
      defined T cell deficiency had elevated endogenous cAMP levels compared with
      controls. Treatment of T cells from these CVI patients with Rp-8-bromo-cAMP
      phosphorothioate markedly improved anti-CD3-stimulated proliferation (up to 3.7
      fold), particularly in CD4+ lymphocytes, reaching proliferation levels comparable
      to control values. No effect of cAMP antagonist on T cell proliferation was seen
      in controls. In these CVI patients, cAMP antagonist also increased IL-2
      production in anti-CD3-stimulated T cells. However, exogenously added IL-2 at
      concentrations comparable to the achieved increase in IL-2 levels after addition
      of cAMP antagonist had no effect on T cell proliferation. Furthermore, the
      stimulatory effects of exogenously added IL-2 at higher concentrations and cAMP
      antagonist on T cell proliferation were additive. Our findings indicate that
      increased PKAI activation may be an important molecular basis for the T cell
      defect in CVI and suggest that the cAMP/PKAI system may be a potential molecular
      target for immunomodulating therapy in these patients.

PMID- 9916751
TI  - Specific V beta T cell subsets are associated with cat and birch pollen allergy
      in humans.
AB  - Cognate interaction between TCRs and MHC class II molecules plays an important
      role in initiating the allergen-specific immune response. Therefore, we analyzed
      the TCR distribution of human PBLs of 56 atopic and nonatopic (NA) individuals,
      including 4 monozygotic twin pairs, from two extended and four nuclear families.
      The expression of 23 V beta and 3 V alpha elements was analyzed. The blood
      samples of symptomatic birch pollen-sensitized individuals that were taken < or =
      6 wk after the birch pollen season (n = 8) showed a significantly higher
      frequency of V beta 16.1+ and V beta 20.1+ T cells compared with the blood
      samples of birch pollen-sensitized individuals that were obtained out of allergen
      season (n = 10) or from NA individuals (p < 0.0005 and p < 0.0001, respectively).
      Allergen-specific lymphocyte proliferation was detected in the allergic
      individuals, and the distribution of V beta 16.1+ and V beta 20.1+ T cells
      returned to normal levels after the pollen season. The frequency of these V beta
      expressing T cells correlated with the levels of allergen-specific IgE Abs. In
      addition, cat-sensitized individuals (n = 8) showed a significantly higher
      frequency of V beta 17.1-expressing T cells than did NA individuals (p < 0.005).
      Our results indicate restricted TCR-V beta gene usage in cat and birch pollen
      allergies; we suggest that both genetic and environmental factors contribute to
      TCR-V beta gene expression and to the development of a specific T cell response.

PMID- 9916752
TI  - A role for perforin in activation-induced T cell death in vivo: increased
      expansion of allogeneic perforin-deficient T cells in SCID mice.
AB  - Despite defective granule exocytosis, T cells from mice whose perforin gene was
      ablated by homologous recombination (pko mice) caused a similar degree of graft
      vs-host disease as normal T cells after injection into sublethally irradiated C.B
      17 SCID mice. Moreover host spleens contained significantly greater numbers of T
      cells from pko mice than from wild-type mice following their i.v. injection. This
      increase could not be explained by persistence of host APCs that were not cleared
      by defective donor cytotoxic effector cells. The absence of functional perforin
      dependent suppressor cells or an altered cytokine profile of donor T cells could
      also not account for the behavior of pko cells. Spontaneous and Fas-mediated
      apoptosis of in vivo activated donor T cells were independent of donor origin.
      However, pko T blasts exhibited less growth inhibition and cell death after
      reactivation in vitro. The results are compatible with a model of a defective
      activation-induced cell death (AICD) pathway, controlled by perforin, accounting
      for the increased expansion of alloreactive pko T cells.

PMID- 9916753
TI  - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation
      polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition
      of TNF-alpha and IL-6.
AB  - The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate
      cyclase-activating polypeptide (PACAP) down-regulate cytokine production. Because
      human septic shock involves excessive cytokine production, the effect of
      VIP/PACAP was investigated in a high endotoxemia murine model. Both peptides
      protect against endotoxin-induced lethality and prevent septic shock-associated
      histopathological alterations. VIP/PACAP reduce serum and peritoneal TNF-alpha
      and IL-6, suggesting that the protective effect is exerted by inhibiting the
      production of endogenous TNF-alpha/IL-6. Consistent with this mechanism, VIP does
      not protect against septic shock induced by exogenous TNF-alpha. The
      immunomodulatory role of VIP in vivo is supported by the appearance of high
      levels of VIP in serum and peritoneal fluid following LPS administration. Thus,
      the neuropeptides VIP/PACAP protect from the lethal effect of high endotoxemia,
      presumably by down-regulating TNF-alpha and IL-6 production, and may offer an
      alternative in the treatment of human septic shock syndrome.

PMID- 9916754
TI  - Rejection of cardiac xenografts by CD4+ or CD8+ T cells.
AB  - We recently showed that brief complement inhibition induces accommodation of
      hamster cardiac transplants in nude rats. We have reconstituted nude rats
      carrying an accommodated xenograft with syngeneic CD4+ or CD8+ T cells to
      investigate the cellular mechanism of xenograft rejection. We show that CD4+ T
      cells can initiate xenograft rejection (10 +/- 1.7 days) by promoting production
      of IgG xenoreactive Abs (XAb). These XAb are able to activate complement as well
      as to mediate Ab-dependent cell-mediated cytotoxicity. Adoptive transfer of these
      XAb into naive nude rats provoked hyperacute xenograft rejection (38 +/- 13 min).
      The rejection was significantly (p < 0.001) delayed by cobra venom factor (CVF;
      11 +/- 8 h in four of five cases) but was still more rapid than in control nude
      rats (3.3 +/- 0.5 days). CVF plus NK cell depletion further prolonged survival
      (>7 days in four of five cases; p < 0.01 vs CVF only). CD8+ T cell-reconstituted
      nude rats rejected their grafts later (19.4 +/- 5.8 days) and required a larger
      number of cells for transfer as compared with CD4+ T cell-reconstituted nude
      rats. However, second xenografts were rejected more rapidly than first xenografts
      in CD8+ T cell-reconstituted nude rats (9 +/- 2 days), indicating that the CD8+ T
      cells had been activated. This study demonstrates that CD4+ and CD8+ T cells can
      both reject xenografts. The CD4+ cells do so at least in part by generation of
      helper-dependent XAb that act by both complement-dependent and Ab-dependent cell
      mediated cytotoxicity mechanisms; the CD8+ cells do so as helper-independent
      cytotoxic T cells.

PMID- 9916755
TI  - A frequency domain approach to nonlinear and structure identification for long
      memory systems: application to lung mechanics.
AB  - From the input-output point of view, many nonlinear biological systems display
      long memory characteristics which can become a critical issue using nonparametric
      time-domain kernel identification due to inevitable truncation of memory length.
      To avoid these limitations, we present an alternative approach in the frequency
      domain with application to lung mechanics. Generally, if the system is excited
      with a periodic wave form, the response will approach a steady state which
      dominates the long memory transients. Thus, we hypothesized that the kernels at
      discrete frequencies will not be significantly affected by memory truncation. To
      test this, we extended the frequency kernel analysis of Victor and Shapley
      (Biophys. J. 29:459-484, 1980) to a nonwhite input spectrum and developed a new
      structure test in the frequency domain to differentiate between Wiener and
      Hammerstein models. These techniques were applied to measured pressure-flow data
      of isolated lung lobes. The results showed that (1) the important nonlinearities
      in the pressure-flow relation are of second order, (2) the frequency kernels of
      the lobes were similar for flat and ventilatory-like input spectra, and (3) the
      structure test strongly suggested that the pressure-flow relationship during
      tidal-like excursions is consistent with a Wiener structure.

PMID- 9916756
TI  - How heterogeneous bronchoconstriction affects ventilation distribution in human
      lungs: a morphometric model.
AB  - Convective dependent flow heterogeneities associated with airways proximal to the
      acini are the dominant cause of abnormal ventilation distribution during induced
      bronchoconstriction (Verbanck, S., D. Schuermans, A. Van Muylem, M. Paira, M.
      Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J.
      Appl. Physiol. 83:1907-1916, 1997). We applied a morphometric model of the human
      lung to predict flow distributions among the acini during heterogeneous
      bronchoconstriction and relate these distributions to impairments in the
      mechanical properties of the lung. The model has an asymmetrical branching airway
      system. Heterogeneous constriction was invoked by defining an airway constriction
      distribution with a mean (mu) and coefficient of variation (CV) and either a
      Gaussian or log normal distribution. The lung resistance (RL) and elastance (EL)
      were most sensitive to severely heterogeneous constriction that produced a few
      highly constricted or closed airways dispersed randomly throughout the periphery.
      Ventilation distribution in the healthy lung was effectively homogeneous over the
      frequency range of 0.1-5.0 Hz. With homogeneous or mildly heterogeneous
      constriction (CV< or =20%) ventilation remained fairly homogeneous at low
      frequencies (< or =0.1 Hz) but rapidly became heterogeneous as frequency
      increased. Conversely, a low mean but severely heterogeneous constriction that
      produced random airway closure produced abnormal ventilation distribution in most
      acini at all frequencies, and some acini received up to 25 times the normal
      ventilation. This suggests that certain forms of heterogeneity can lead to shear
      induced lung injury even at common mechanical ventilation rates.

PMID- 9916757
TI  - Nonlinear analysis of renal autoregulation in rats using principal dynamic modes.
AB  - This article presents results of the use of a novel methodology employing
      principal dynamic modes (PDM) for modeling the nonlinear dynamics of renal
      autoregulation in rats. The analyzed experimental data are broadband (0-0.5 Hz)
      blood pressure-flow data generated by pseudorandom forcing and collected in
      normotensive and hypertensive rats for two levels of pressure forcing (as
      measured by the standard deviation of the pressure fluctuation). The PDMs are
      computed from first-order and second-order kernel estimates obtained from the
      data via the Laguerre expansion technique. The results demonstrate that two PDMs
      suffice for obtaining a satisfactory nonlinear dynamic model of renal
      autoregulation under these conditions, for both normotensive and hypertensive
      rats. Furthermore, the two PDMs appear to correspond to the two main
      autoregulatory mechanisms: the first to the myogenic and the second to the
      tubuloglomerular feedback (TGF) mechanism. This allows the study of the separate
      contributions of the two mechanisms to the autoregulatory response dynamics, as
      well as the effects of the level of pressure forcing and hypertension on the two
      distinct autoregulatory mechanisms. It is shown that the myogenic mechanism has a
      larger contribution and is affected only slightly, while the TGF mechanism is
      affected considerably by increasing pressure forcing or hypertension (the
      emergence of a second resonant peak and the decreased relative contribution to
      the response flow signal).

PMID- 9916758
TI  - Accuracy of computational hemodynamics in complex arterial geometries
      reconstructed from magnetic resonance imaging.
AB  - PURPOSE: Combining computational blood flow modeling with three-dimensional
      medical imaging provides a new approach for studying links between hemodynamic
      factors and arterial disease. Although this provides patient-specific hemodynamic
      information, it is subject to several potential errors. This study quantifies
      some of these errors and identifies optimal reconstruction methodologies.
      METHODS: A carotid artery bifurcation phantom of known geometry was imaged using
      a commercial magnetic resonance (MR) imager. Three-dimensional models were
      reconstructed from the images using several reconstruction techniques, and steady
      and unsteady blood flow simulations were performed. The carotid bifurcation from
      a healthy, human volunteer was then imaged in vivo, and geometric models were
      reconstructed. RESULTS: Reconstructed models of the phantom showed good agreement
      with the gold standard geometry, with a mean error of approximately 15% between
      the computed wall shear stress fields. Reconstructed models of the in vivo
      carotid bifurcation were unacceptably noisy, unless lumenal profile smoothing and
      approximating surface splines were used. CONCLUSIONS: All reconstruction methods
      gave acceptable results for the phantom model, but in vivo models appear to
      require smoothing. If proper attention is paid to smoothing and geometric
      fidelity issues, models reconstructed from MR images appear to be suitable for
      use in computational studies of in vivo hemodynamics.

PMID- 9916759
TI  - A "geographic information systems" based technique for the study of microvascular
      networks.
AB  - An automated system (ANET) has been developed to construct interactive maps of
      microvascular networks, calculate blood flow parameters, and simulate
      microvascular network blood flow using the geographic information systems (GIS)
      technology. ANET enables us to automatically collect and display topological,
      structural, and functional parameters and simulate blood flow in microvascular
      networks. The user-definable programming interface was used for the manipulation
      of drawings and data. Visual enhancement techniques such as color can be used to
      display useful information within a network. In ANET the network map becomes a
      graphical interface through which network information is stored and retrieved and
      simulations of microvascular network blood flow are carried out. We have used
      ANET to study the effects of ionizing radiation on normal tissue microvascular
      networks. Our results indicate that while vessel diameters significantly
      increased with age in control animals they decreased in irradiated animals. The
      tortuosity of irradiated vessels (16.3+/-1.1 mean+/-standard error of the mean)
      was significantly different from control vessels (10.0+/-1.3) only at 7 days
      postirradiation. Average red blood cell transit time was significantly different
      between control (1.6+/-0.6s) and irradiated (10.7+/-5.7s) microvascular networks
      at 30 days postirradiation. ANET provides an effective tool for handling the
      large volume of complex data that is usually obtained in microvascular network
      studies and for simulating blood flow in microvascular networks.

PMID- 9916760
TI  - Selective stimulation of latissimus dorsi muscle for cardiac assist.
AB  - The contractile power of the latissimus dorsi muscle (LDM) is used in skeletal
      muscle cardiac assist (SMCA) to augment the blood pumping ability of a failing
      heart. The LDM has three anatomically distinct, independently innervate segments
      the transverse, oblique, and lateral. There are potential advantages to
      selectively stimulating these LDM regions. We hypothesized that (1) the three
      nerve branches could be stimulated selectively to activate individual muscle
      regions with little or no functional overlap, (2) the three muscle regions would
      generate similar force, and (3) nerves stimulated in combinations would generate
      forces corresponding to the sum of forces generated by the individual regions. In
      acute studies of canine LDM (n=5), regional electromyogram (EMG) and isometric
      force were recorded while branches of the thoracodorsal nerve were stimulated
      (via nerve-cuff electrodes) individually and in combinations. Analysis of
      regional EMG and force confirmed selective activation. Stimulation of lateral,
      oblique, and transverse branches of thoracodorsal nerve activated 53+/-5%, 20+/
      9%, and 36+/-9% of the muscle, respectively; with corresponding developed forces
      of 48+/-6%, 21+/-8%, and 31+/-8% of total muscle force (R=0.98, p<0.05).
      Selective activation of LDM is possible with little or no functional overlap;
      however, the muscle regions were nonuniform. Selective stimulation may ultimately
      facilitate the use of performance enhancing stimulus protocols for SMCA.

PMID- 9916761
TI  - Microvascular thermal equilibration in rat spinotrapezius muscle.
AB  - The current study investigates heat exchange in the thermally significant
      countercurrent paired vessels of the rat spinotrapezius muscle. Detailed tissue
      surface temperatures under normal (after the microvascular surgery) and
      pharmacologically vasodilated states were measured using high-resolution infrared
      thermography. During vasodilation, a measurable thermal disturbance was observed
      above the first-order feeding vessel pair. The measured tissue temperatures were
      compared with those predicted by modifying the theoretical model for two
      dimensional muscle preparations given by Zhu et al. (Zhu, L., D. E. Lemons, and
      S. Weinbaum. Ann. Biomed. Eng. 24:109-123, 1996). They were found in good
      agreement. The Weinbaum-Jiji k(eff) theory (Weinbaum, S., and L. M. Jiji. J.
      Biomech. Eng. 107:131-139, 1985) for heat exchange between the paired vessels and
      their surrounding tissue was also examined in this muscle. A close agreement was
      obtained between the theoretically predicted k(eff) and the measured value
      calculated using a fin approximation for the tissue layer. This experimental
      study revealed for the first time the nonequilibration between blood vessels and
      the surrounding tissue, where the enhancement in k(eff) due to the incomplete
      countercurrent heat exchange is comparable to the tissue axial conduction.

PMID- 9916762
TI  - Cyclic traction machine for long-term culture of fibroblast-populated collagen
      gels.
AB  - Our research group has been investigating the effect of cyclic deformations on
      the evolution of fibroblast populated collagen gels (FPCG). Since existing
      traction machines are not designed for such an application, we had to design a
      cyclic traction machine adapted to tissue culture inside an incubator over an
      extended period of time. Biocompatible materials were used for fabrication to
      allow for easy sterilization and to prevent any adverse reaction from the tissue.
      The traction machine is based on a computer-controlled stepping motor system for
      easy adjustment of the deformation amplitude and frequency. The maximum
      stretching speed achieved is around 1 mm/s. The traction machine can measure FPCG
      mechanical properties and perform rupture tests to determine its ultimate
      strength. Several FPCGs have been successfully cultured with the machine for up
      to four weeks without any adverse reaction.

PMID- 9916763
TI  - Wideband inhibition of dorsal cochlear nucleus type IV units in cat: a
      computational model.
AB  - A computational model of a portion of dorsal cochlear nucleus neural circuitry
      was used to investigate relationships between connectivity and response
      properties of type IV units. The model in this study consists of four neural
      populations. The pattern of convergence from one population to another and the
      strengths of those connections are the most important model parameters. Lumped
      parameter electrical circuit models represent individual cells. Interconnections
      are achieved by activating variable conductances in post-synaptic cells according
      to spike activity in pre-synaptic cells. Auditory nerve fibers are incorporated
      as a bank of logarithmically spaced gammatone filters that drive compartmental
      models of inner hair cell function. While it might be possible to configure the
      model without wideband inhibition to simulate type IV unit notch noise responses,
      the resulting parameters would likely be physiologically implausible. The model
      with wideband inhibition, however, shows the appropriate notch noise behavior. A
      wide variety of simulated rate versus cutoff-frequency plots are achieved varying
      three model parameters. The model was fit to physiological data by finding values
      of these three parameters that minimize the sum of squared errors. The results
      show that wideband inhibition can quantitatively account for the responses of
      type IV units to notch noise.

PMID- 9916764
TI  - Filter banks and neural network-based feature extraction and automatic
      classification of electrogastrogram.
AB  - Dysrhythmia in gastric myoelectrical activity has been frequently observed in
      patients with gastric motor disorders and gastrointestinal symptoms. The
      assessment of the regularity of gastric myoelectrical activity is of great
      clinical significance. The aim of this study was to develop an automated
      assessment method for the regularity of gastric myoelectrical activity from the
      surface electrogastrogram (EGG). The method proposed in this paper was based on
      the filter bank and neural network. First, the EGG signal was divided into
      frequency subbands using filter bank analysis. Second, a parameter called the
      subband energy ratio (SER) was computed for each subband signal. A multilayer
      perceptron neural network was then used to automatically classify the EGG signal
      into four categories: bradygastria, normal, tachygastria, and arrhythmia, using
      the SER as the input. The EGG recording was made using the standard method of
      electrogastrography by placing electrodes on the abdominal surface. The study was
      performed in 40 patients with various gastric motor disorders, ten healthy
      adults, and ten healthy children. The neural network was trained and tested using
      the EGG data obtained from the patients. The regularity of gastric myoelectrical
      activity was assessed based on the classification of the minute-by-minute EGG
      segments. Using the running spectral analysis method as a gold standard, the
      proposed automated method had an accuracy of 100% for the training set and 97%
      for the test set. It was concluded that the proposed method provides an accurate
      and automatic assessment of the regularity of gastric myoelectrical activity from
      the EGG.

PMID- 9916765
TI  - Effective epicardial resistance of rabbit ventricles.
AB  - This study evaluated effective resistances on the ventricular surfaces of
      arterially-perfused rabbit hearts. Effective resistances were determined with a
      four-electrode array that was parallel or perpendicular to epicardial fibers.
      Resistance along or across epicardial fibers was determined by applying current
      to the epicardium with two parallel line electrodes and measuring potentials in
      the region between the electrodes. Computer simulations were performed to gain
      insight into the distribution of current in the ventricular wall. The effective
      resistances were not different along versus across fibers. Simulations showed
      that transmural rotation of fibers causes current to be distributed differently
      when the electrode is oriented perpendicular versus parallel to epicardial
      fibers. When the array is oriented so that epicardial current is across fibers,
      the fraction of current that flows transmurally and along the deeper fibers
      increases while the fraction of current that flows epicardially decreases. This
      introduces isotropy of the effective resistance. Thus, in contrast to isolated
      cardiac fibers, the ventricular epicardium exhibits isotropic effective
      resistance due to transmural rotation of fibers. The rotation and isotropic
      resistance may be important for cardiac electrical behavior and effects of
      electrical current in the ventricles.

PMID- 9916766
TI  - Assessment of the directional elastic moduli of ewe vertebral cancellous bone by
      vibrational testing.
AB  - The ovariectomized ewe is being used as an animal model for postmenopausal
      osteoporosis. Data on the mechanical properties of ewe vertebral cancellous bone
      is needed to assess its effectiveness as a model for vertebral osteoporosis. This
      study utilized traditional compression testing and a novel nondestructive
      vibrational testing method to assess the directional mechanical properties of ewe
      vertebral cancellous bone. Composition and density properties were also assessed.
      It was hypothesized that vibrational testing would have utility in that it would
      allow for the anisotropic stiffness of cancellous bone to be assessed
      nondestructively. The present study has found that ewe vertebral cancellous bone
      has similar physical and mechanical properties to humans. The vibrational testing
      method described was able to nondestructively provide a valid measure of
      stiffness that was correlated with stiffness estimates from traditional
      compression testing. Furthermore, the stiffness measure from the vibration test
      was found to be sensitive to the architecture of cancellous bone. These results
      suggest the promise of this testing method for the nondestructive mechanical
      assessment of skeletal tissue.

PMID- 9916767
TI  - Zirconia as a ceramic biomaterial.
AB  - Zirconia ceramics have several advantages over other ceramic materials, due to
      the transformation toughening mechanisms operating in their microstructure that
      can give to components made out of them, very interesting mechanical properties.
      The research on the use of zirconia ceramics as biomaterials started about twenty
      years ago, and now zirconia (Y-YZP) is in clinical use in THR, but developments
      are in progress for application in other medical devices. Recent developments
      have concentrated on the chemistry of precursors, in forming and sintering
      processes, and on surface finish of components. Today's main applications of
      zirconia ceramics is in THR ball heads. This review takes into account the main
      results achieved up to now, and is focused on the role that microstructural
      characteristics play on the TZP ceramics behaviour in ball heads, namely
      mechanical properties and their stability, wear of the UHMWPE paired to TZP, and
      their influence on biocompatibility.

PMID- 9916768
TI  - Biocompatibility studies of anionic collagen membranes with different degree of
      glutaraldehyde cross-linking.
AB  - The work describes the biocompatibility and biodegradation studies of anionic
      collagen membranes casted form collagen gels collagen, that were selective
      hydrolyzed at the carboxyamide groups, as a function of the degree of cross-links
      induced by glutaraldehyde. Independently from the degree of cross-links, all
      membranes studied were characterized by a similar inflammatory response,
      inversely dependent on glutaraldehyde reaction time, that decreased from the time
      of the implant. Cell alterations, mineralization or contact necrosis were not
      observed in any of the membranes studied. Rates for membrane tissue
      biodegradation were directly related to glutaraldehyde reaction time, and ranged
      from 30 to periods longer than 60 days, associated with good biocompatibility.
      Although other properties must be considered, their use in the treatment of
      periodontal diseases, the biological behavior observed with the 8 h GA cross
      linked membrane suggests that, anionic collagen membrane described in this work
      may be of potential use, not only in association with guided tissue regeneration
      technique for periodontal tissue reconstruction, but also in other collagen
      biomaterial applications where controlled biodegradability is required.

PMID- 9916769
TI  - Further investigations on the hydrolytic degradation of poly (DL-lactide).
AB  - The hydrolytic degradation of poly(DL-lactide) (PLA50) material was investigated
      in order to elucidate the effects of temperature and acidity of the external
      medium on the degradation characteristics. It was observed that at 60 degrees C
      and at pH = 7.4, degradation was extremely rapid as compared with degradation at
      37 degrees C. After only 2 days, heterogeneous degradation was observed due to
      larger internal autocatalysis. On the other hand, in the case of degradation at
      37 degrees C in an acidic medium with pH = 3.7, the heterogeneous degradation was
      preceded by a much longer lag time. Water absorption was found to be pH
      dependent. At pH = 7.4, water absorption was increased due to the osmotic
      pressure driving the buffer solution into the polymer matrix to neutralize acidic
      endgroups, which was not the case for degradation at pH = 3.7. In both cases, the
      oligomeric stereocomplex was obtained as degradation residue at the end of the
      degradation period.

PMID- 9916771
TI  - Soft acrylic resin materials containing a polymerisable plasticiser II: water
      absorption characteristics.
AB  - The main disadvantage of soft acrylic resin denture lining materials is the loss
      of plasticiser leading to gradual hardening. One possible solution to this
      problem is the use of a polymerisable plasticiser. A material based on such a
      plasticiser failed in clinical trials due to a combination of prolonged water
      uptake and low strength. Similar materials with improved strength have been
      developed and it is the aim of this study to investigate their water uptake
      characteristics. Water uptake from distilled water, an artificial saliva and 0.9
      M saline has been determined for three experimental materials and 'Supersoft', a
      commercial plasticised acrylic resin denture lining material. Solubilities were
      determined after 6 months and diffusion coefficients calculated where
      appropriate. All the experimental materials had a lower uptake and solubility
      than 'Supersoft' in all solutions. For each material uptake was lower from
      solution than from distilled water. All diffusion coefficients were in the range
      expected for this type of material. The water uptake of the experimental
      materials was influenced by the relative hydrophilicity of the monomer used.

PMID- 9916770
TI  - Alginate hydrogels as synthetic extracellular matrix materials.
AB  - Alginate hydrogels are used extensively in cell encapsulation, cell
      transplantation, and tissue engineering applications. Alginates possess many
      favorable properties required in biomaterials, but are unable to specifically
      interact with mammalian cells. We have therefore covalently modified alginate
      polysaccharides with RGD-containing cell adhesion ligands utilizing aqueous
      carbodiimide chemistry. The chemistry has been optimized and quantified with
      reaction efficiencies reaching 80% or greater. The concentration of peptide
      available for reaction was then varied to create hydrogels with a range of ligand
      densities. Mouse skeletal myoblasts were cultured on alginate hydrogel surfaces
      coupled with GRGDY peptides to illustrate achievement of cellular interaction
      with the otherwise non-adhesive hydrogel substrate. Myoblasts adhere to GRGDY
      modified alginate surfaces, proliferate, fuse into multinucleated myofibrils, and
      express heavy-chain myosin which is a differentiation marker for skeletal muscle.
      Myoblast adhesion and spreading on these GRGDY-modified hydrogels was inhibited
      with soluble ligand added to the seeding medium, illustrating the specificity of
      adhesion to these materials. Alginate may prove to be an ideal material with
      which to confer specific cellular interactive properties, potentially allowing
      for the control of long-term gene expression of cells within these matrices.

PMID- 9916772
TI  - Development of fungal mycelia as skin substitutes: effects on wound healing and
      fibroblast.
AB  - In this study, Sacchachitin membrane, prepared from the residue of the fruiting
      body of Ganoderma tsugae, was estimated for its effects on wound healing and the
      proliferation and migration of fibroblast cells. Two mirror-image wounds were
      made on the back of female guinea pigs by dissecting a 1.5 x 1.5 cm2 skin surface
      of full thickness. Sacchachitin membrane was placed randomly on one of the wounds
      and gauze or Beschitin on the other. Changes in the wound area were measured and
      photographed after a predetermined amount of time postoperatively. Histological
      examination of the wound and surrounding tissue was also performed to reveal any
      interaction of tissue with the dressing. The results showed that the wound area
      covered with Sacchachitin membrane was statistically smaller than that covering
      with gauze on day 10, whereas there was no significant difference in the wound
      size compared to that with Beschitin. Fibroblast cells from the dermis layer of
      guinea pigs were used. The number of fibroblast cells were counted on the
      predetermined days in the culture suspended with or without 0.01% w/v dressing
      materials. By layering on DMEM plates, the number of fibroblast cells migrating
      across the center line or outside of the central hole were counted after five
      days. All the results indicated that both 0.01% w/v of Sacchachitin and chitin
      significantly enhanced the proliferation and migration of fibroblast cells.

PMID- 9916773
TI  - Apparent fracture toughness of acrylic bone cement: effect of test specimen
      configuration and sterilization method.
AB  - The plane strain fracture toughness of Palacos R bone cement was determined using
      linear elastic fracture mechanics (LEFM) principles and three different test
      specimen configurations: single edge notched three-point (SENB), rectangular
      compact tension (RCT), and chevron notched short rod (CNSR). Another aspect of
      the study was an investigation of the effect of three methods used to sterilize
      the powder constituents of the cement-none, gamma irradiation and ethylene oxide-
      on the fracture toughness of the fully polymerized material. A detailed
      justification is provided for using LEFM. The fracture toughness results obtained
      using the CNSR specimens were, on average, 14 and 16% higher than those obtained
      using the SENB and RCT types, respectively. These differences are accounted for
      in terms of differences in four aspects of these specimen configuration (namely,
      residual stress effects, loading rate, material inhomogeneity, and the nature of
      the test). For a given specimen configuration, gamma irradiation produced a
      statistically significant decrease in fracture toughness which, it is suggested,
      is due to the concomitant depreciation in molecular weight. For a given cement
      type, there is no statistically significant difference in fracture toughness
      results obtained using SENB and RCT specimens. It is thus suggested that either
      of these configurations can be used to determine the fracture toughness of
      acrylic bone cement.

PMID- 9916774
TI  - Sol-gel modification of silicone to induce apatite-forming ability.
AB  - Silicones formed with silanol groups on their surfaces were prepared by partial
      hydrolysis and polycondensation of tetraethoxysilane (TEOS) dispersed in
      silicones in molecular scale. Although the silanol-modified silicones thus
      prepared formed no apatite in a simulated body fluid (SBF) with ion
      concentrations nearly equal to those of human blood plasma within 21 d, they
      formed a bone-like apatite layer in situ on their surfaces in a solution (1.5
      SBF) with ion concentrations 1.5 times the SBF within 7 d. This indicates that
      the silanol groups formed on the silicones by the present method can induce the
      apatite nucleation in 1.5 SBF and hence, apatite-coated silicones can be
      fabricated by a biomimetic process. Apatite-silicone composites thus prepared
      could exhibit mechanical properties analogous to the natural bone as well as
      bioactivity.

PMID- 9916775
TI  - Morsellized bone grafting compensates for femoral bone loss in revision total
      knee arthroplasty. An experimental study.
AB  - This study was undertaken to examine the contribution of uncontained morsellized
      bone graft to the structural properties of a femoral reconstruction in total knee
      arthroplasty and to serve as a basis for an in vivo animal study. Ten human
      distal femora with a standard unicondylar uncontained medial bone defect were
      prepared to fit a femoral component of a cruciate sacrificing TKA. A cyclic axial
      load of 750 N was applied to the medial part of the femoral component in the
      presence of impacted morsellized bone graft. After removal of the bone graft, the
      cyclic loading was repeated for the unsupported situation. None of the grafts
      collapsed and all cement mantles stayed intact during the experiments. Elastic
      deformation during cyclic loading was significantly less when graft was added
      while time-dependent deformation was not affected. We conclude that impacted
      morsellized bone graft, used for reconstruction of uncontained femoral bone loss
      in revision knee arthroplasty, may improve the structural resistance against
      loading. Further animal experimentation for in vivo application is warranted.

PMID- 9916776
TI  - Polyphosphazene membranes and microspheres in periodontal diseases and implant
      surgery.
AB  - Membranes or microcapsules made from polyphosphazenes bearing amino acid side
      groups are proposed for the treatment of periodontal diseases. Polyphosphazene
      membranes, prepared with alanine ethyl ester and imidazole in the molar ratio of
      80:20 as phosphorus substituents, gave a degradation rate that corresponded to
      the healing of the bone defect. These membranes were much more successful in
      promoting healing of rabbit tibia defects than polytetrafluoroethylene membranes.
      Antibacterial or anti-inflammatory drugs, useful in periodontal tissue
      regeneration, could be entrapped in the polyphosphazene membranes and released
      both in vitro and in vivo at a rate that ensured therapeutic concentrations in
      the surrounding tissue. Polyphosphazene microspheres, prepared with phenylalanine
      ethyl ester as a phosphorus substituent and loaded with succinylsulphathiazole or
      naproxen, were also obtained. The kinetics of release from these matrices were
      very convenient in yielding local concentrations of the two drugs that are useful
      per se or when mixed with hydroxyapatite for better bone formation.

PMID- 9916778
TI  - Immunofluorescent localization of estrogen receptor-alpha in growth plates of
      rabbits, but not in rats, at sexual maturity.
AB  - Estrogens are considered essential to the mechanism for closure of epiphyses in
      both males and females. The mechanism for this, however, is still unclear. It is
      likely that estrogen acts directly on growth plate chondrocytes, but the
      localization of the cells expressing the estrogen receptor (ER) has yet to be
      ascertained. Moreover, in rodents, growth plates remain open well into adult
      life. Whether the distribution of estrogen target cells in rodent epiphyses
      differs from that in other species, is also unclear. We therefore compared
      localization of estrogen target cells (denoted by ER-alpha protein expression) in
      species in which growth plates fuse, with that in rodents. Thus, we have
      investigated ER-alpha protein expression in femoral growth plates from male and
      female rabbits, just at sexual maturity (6 months), when growth plate fusion was
      just commencing, and in rats of equivalent developmental stage (9 weeks). ER
      alpha was detected in undecalcified cryosections by immunofluorescence with 1D5
      monoclonal antibody, raised to human ER-alpha; uterine sections were positive
      controls. ER-alpha-positive cells were localized to the proliferative/early
      hypertrophic zone of male and female rabbits. By contrast, cells in the similar
      region of the mature rat growth plate were ER-alpha-negative in both genders,
      although receptor could be readily detected in uteri of mature female rats. In
      growth plates of immature male and female rats (6 weeks), however, ER-alpha was
      clearly expressed by cells of the proliferative/early hypertrophic zone, but was
      barely detectable in uteri from immature females. Our findings support the view
      that estrogen may act directly on the growth plate and, in species in which there
      is epiphyseal fusion, may thus have a role in this process. If ER-alpha
      expression is lost at sexual maturity, as in rodents, growth plates may remain
      open into adulthood. Our results also show the changes in ER-alpha expression in
      growth plates of maturing rats may be opposite to that in the uterus and raise
      the possibility that receptor expression may be controlled differently in
      reproductive and skeletal tissues.

PMID- 9916777
TI  - In vivo expression of transcripts encoding the Glvr-1 phosphate
      transporter/retrovirus receptor during bone development.
AB  - In vitro observations suggest that inorganic phosphate (Pi) transport plays an
      important functional role in osteogenic cells and in their matrix vesicles for
      the initiation of matrix calcification. Recent studies have shown that the type
      III sodium-dependent Pi transporters, Glvr-1 and Glvr-2, are expressed in human
      osteoblast-like cells and have suggested a potential role for type III
      transporters in regulated Pi handling in osteogenic cells. To address the
      relevance of these findings in the context of bone formation in vivo and, in
      particular, in relation to matrix calcification, we investigated expression of
      the Glvr-1 transporter by in situ hybridization in developing embryonic murine
      metatarsals, using human Glvr-1 cDNA as a probe. In this model of endochondral
      ossification, expression of transcripts encoding Glvr-1 could be detected from
      day 17 of embryonic development. A hybridization signal for Glvr-1 was
      specifically observed in a subset of hypertrophic chondrocytes and could not be
      detected in osteoblasts. The expression of Glvr-1 mRNA was compared with that of
      transcripts encoding extracellular matrix proteins. Glvr-1 mRNA expression was
      confined to a population of early hypertrophic chondrocytes expressing type X
      collagen and to slightly more mature cells that express transcripts encoding
      osteopontin but lack type X collagen mRNA. No Glvr-1 transcripts were detected in
      fully differentiated hypertrophic chondrocytes. This pattern of Glvr-1 mRNA
      expression was maintained throughout embryonic development until after birth. In
      conclusion, the Glvr-1 phosphate transporter is selectively expressed in a subset
      of hypertrophic chondrocytes during endochondral bone formation, in a region
      where matrix mineralization proceeds. This observation represents the first in
      vivo evidence consistent with a potential role for this phosphate transporter in
      matrix calcification.

PMID- 9916779
TI  - Skeletal effects of aging in male rhesus monkeys.
AB  - Age-related bone loss in men is receiving increased attention. In light of this,
      animal models for male bone loss are desirable. This study examined the effects
      of age and osteoarthritis (OA) on bone mineral content (BMC), bone mineral
      density (BMD), and markers of bone turnover and skeletal relevance in 56 male
      rhesus monkeys 4-34 years of age. BMC and BMD increased at all sites from 4 to 10
      years of age. Male rhesus monkeys reach peak bone mass at approximately 10 years
      of age after which bone mass is lower at the lateral spine and distal radius.
      Markers of bone turnover (osteocalcin and carboxyterminal telopeptide of type I
      collagen [ICTP]) decreased with age. There was no relationship between PTH, 25
      hydroxyvitamin D, FSH, or testosterone and age. With advancing age, the
      prevalence of lumbar spine OA increases dramatically, masking decreases in
      posteroanterior spine bone mass that are clear in the lateral projection. These
      data suggest that male rhesus monkeys sustain age-related bone loss in the
      absence of nutritional or gonadal steroid deficiencies. These animals may prove
      useful in studying the mechanisms of age-related bone loss.

PMID- 9916780
TI  - Histomorphometry and bone biomarkers in cynomolgus females: a study in young,
      mature, and old monkeys.
AB  - Although ovariectomized cynomolgus monkeys are used extensively for studies
      examining perimenopausal changes in the skeleton, very little is known about the
      changes that occur naturally during growth and aging in these animals. To
      evaluate the changes in bone during growth and aging in female cynomolgus
      monkeys, 29 monkeys ranging from 3 years to >22 years of age were given a bone
      fluorochrome label and iliac biopsies were collected. Serum and urine were
      collected at the time of biopsy to determine alkaline phosphatase (ALP),
      osteocalcin, tartrate-resistant acid phosphatase (TRAP), serum and urinary
      calcium, estradiol, urinary creatinine, and urinary CrossLaps levels. The
      biopsies from 8 young (3-4 years of age), 13 mature (11-16 years of age) and 8
      old (>22 years of age) were analyzed histomorphometrically. ALP, TRAP, and
      urinary CrossLaps levels were lower in the mature and old monkeys when compared
      with the young group. Urinary calcium/urinary creatinine levels increased with
      age. Bone volume (BV/TV), trabecular number (Tb.N), bone formation rate (BFR),
      and activation frequency (Ac.f) were greatest in the young monkeys and declined
      in the older groups. The biomarker and histomorphometric indices in the young
      animals reflect the growth that was occurring in this group. The older monkeys do
      not appear to differ significantly between 10 and 22 years of age.

PMID- 9916781
TI  - Central region-of-interest analysis of lumbar spine densitometry demonstrates
      lower bone mass in older rhesus monkeys.
AB  - Osteoarthritis (OA) spuriously elevates spine bone mineral density (BMD) as
      measured by dual-energy X-ray absorptiometry (DXA). This study documents spinal
      OA prevalence in adult female rhesus monkeys, and evaluates a custom central
      region-of-interest (CROI) analysis technique designed to minimize OA effects on
      BMD measurement. Lumbar spine radiographs were obtained on 71 animals, age 10-37
      years. OA degree was blindly scored as none, minimal, or moderate/severe.
      Moderate/severe OA was not observed before age 19, but was present in 66% of
      older animals. Subsequently, lumbar spine (L2-4) BMD was determined by standard
      DXA analysis and manual placement of 0.92 cm2 CROIs in two groups of female
      rhesus monkeys. One group (eight control, eight postovariectomy, ages 10-19
      years) was assessed longitudinally, the second (n = 90, ages 10-37) cross
      sectionally. Measured bone loss following ovariectomy (8.1% standard analysis,
      11.5 % CROI) was comparable with both techniques. By contrast, CROI demonstrated
      lower bone mass with age (p < 0.0001), whereas only a trend (p = 0.06) was
      observed with standard analysis. When World Health Organization criteria were
      applied, 42% of animals > or = age 19 years were classified as
      osteopenic/osteoporotic by standard analysis compared with 67% by CROI. All
      "normal" animals reclassified as osteopenic/osteoporotic by CROI had OA. In
      conclusion, female rhesus monkeys often develop spinal OA with advancing age.
      CROI analysis demonstrated lower bone density in older monkeys and was as
      sensitive to estrogen-depletion bone loss as standard methodology. This suggests
      that alternative analysis techniques, such as CROI, may be more appropriate to
      evaluate bone density in nonhuman primates, and potentially in people.

PMID- 9916782
TI  - Calibration of trabecular bone structure measurements of in vivo three
      dimensional peripheral quantitative computed tomography with 28-microm-resolution
      microcomputed tomography.
AB  - It has recently been shown that high-resolution computed tomography and magnetic
      resonance imaging have the potential to assess information about the
      microarchitecture of bone in a noninvasive way. However, due to the limited
      spatial resolution of the in vivo measurements, the individual trabeculae are not
      depicted with their true thickness. Nevertheless, the spacing of the structural
      elements allows the assessment of trabecular number. In a previous publication,
      the ridge number density (RND) was introduced as a measure for this structural
      index. It can be extracted from high-resolution three-dimensional (3D) images of
      patients and shows a reproducibility of 1.6%. In this work the Ridge extraction
      procedure is compared to and calibrated with microcomputed tomography (microCT)
      measurements. Three-dimensional measurements of 15 bone biopsies are made with a
      28-microm-resolution microCT scanner as well as with a 165-microm-resolution
      peripheral quantitative computed tomography (pQCT) scanner. For the latter, the
      same settings are used as for patient examinations. The 15 pairs of measurements
      are analyzed and the resulting structural indices are compared. The results show
      that structural indices such as trabecular number, mean thickness, and mean
      separation can be determined from the 3D pQCT data with an r2 of between 0.81 and
      0.96 if the microCT data are taken as the gold standard. The calibration equation
      found for the bone volume fraction has an intercept of 0.04 and a slope of 0.86
      (r2 = 0.98), and trabecular number as the main additional structural index shows
      a nonsignificant intercept and a calibration slope of 0.91 with the microCT. The
      calibration procedure can be used directly for patient examinations. Applied to
      time-series measurements it may be of value for monitoring and quantifying
      microarchitectural changes due to therapy or aging.

PMID- 9916783
TI  - Droloxifene does not blunt bone anabolic effects of prostaglandin E2, but
      maintains prostaglandin E2-restored bone in aged, ovariectomized rats.
AB  - Droloxifene (DRO) is a selective estrogen receptor modulator that prevents bone
      loss by inhibition of bone turnover associated with estrogen deficiency in both
      growing and aged female rats. The purposes of this study were to test: (a)
      whether DRO can maintain prostaglandin E2 (PGE2)-restored bone after
      discontinuation of PGE2 in aged, ovariectomized (ovx) rats; (b) if an inhibition
      of bone turnover by DRO reduces bone anabolic effects of PGE2; and (c) whether
      bone mass restored by PGE2 plus DRO can be maintained after discontinuation of
      both agents. Female rats at 12 months of age were sham-operated (sham) or ovx.
      Three months postsurgery, ovx rats were treated with either PGE2 (3 mg/kg per
      day, subcutaneously [s.c.]) alone, or PGE2 plus DRO (10 mg/kg per day, per os
      [p.o.]) for 2 months. Thereafter, the PGE2 or PGE2 plus DRO treatment was
      withdrawn and the rats were then treated with either vehicle or DRO for another
      1.5 months. Using dual-energy X-ray absorptiometry (DXA), total lumbar vertebral
      bone mineral density (LV-BMD) was determined in vivo at months 0, 3, 5, and 6.5.
      At the end of the study, the rats were autopsied, and BMD of total femur, femoral
      shaft, distal femoral metaphysis, and proximal femur was determined ex vivo by
      DXA. Standard static and dynamic bone histomorphometric parameters were
      determined on the fourth lumbar vertebral body (L-4). At 3, 5, or 6.5 months
      postsurgery, LV-BMD decreased significantly (-15%, -19%, and -19%, respectively)
      in the vehicle-treated ovx rats compared with sham. Beginning at 3 months post
      ovx, PGE2 alone or in combination with DRO for 2 months completely restored LV
      BMD back to the sham level. There was no difference in LV-BMD in PGE2 alone or
      PGE2 plus DRO. Upon cessation of PGE2 treatment, a significant decrease in LV-BMD
      was observed in the PGE2-alone group (-12%). On the other hand, when DRO
      treatment was given after discontinuation of PGE2, the PGE2-restored LV-BMD was
      completely maintained. In the PGE2 plus DRO group, no loss in LV-BMD was observed
      after cessation of either PGE2 alone or both PGE2 and DRO. However, treatment
      with DRO following 2 months of PGE2 plus DRO further increased LV-BMD (+10%). At
      the end of the study, ex vivo femoral BMD data confirmed the observation in
      lumbar vertebrae. Histomorphometric results of L-4 indicated that loss in bone
      mass after cessation of PGE2 in PGE2 alone group was associated with increased
      bone turnover. Treatment with DRO in the maintenance phase inhibited bone
      turnover and prevented bone loss induced by withdrawal of PGE2. Trabecular bone
      mass was maintained in the PGE2 plus DRO followed by vehicle group and further
      increased in the PGE2 plus DRO followed by DRO groups. We found that: (a) DRO is
      efficacious in maintaining PGE2-restored bone after discontinuation of PGE2; (b)
      DRO did not blunt the anabolic effects of PGE2; (c) bone loss occurred after
      cessation of treatment in the PGE2-alone group, whereas it was maintained after
      cessation of treatment in PGE2 plus DRO group; and (d) an additional anabolic
      effect was found in ovx rats treated with PGE2 plus DRO followed by DRO.

PMID- 9916784
TI  - Secondary osteoporosis and the risk of vertebral deformities in women.
AB  - Among an age-stratified sample of 942 Rochester, MN women, the overall prevalence
      of any vertebral deformity, as assessed by radiographic morphometry, was 21.3 per
      100. The prevalence increased with age and, after adjusting for age, vertebral
      deformities were independently associated with height, weight, a history of
      distal forearm or hip fractures, and anticoagulant use. Altogether, 73% of the
      women with a vertebral deformity and 66% of controls had one or more of the
      conditions that have been linked with secondary osteoporosis, which in aggregate
      were associated with an age-adjusted 1.2-fold (95% CI 0.8-1.7) increase in risk
      that was not statistically significant. The prevalence of severe vertebral
      deformities was 11.7 per 100 women and the prevalence of very severe deformities
      was 5.7 per 100. There was a stronger relationship of age and most other risk
      factors with severe vertebral deformities than with isolated mild deformities,
      suggesting that a subset of mild deformities may not represent actual vertebral
      fractures. The metabolic disorders linked with secondary osteoporosis were
      associated with little increase in the risk of severe vertebral deformities,
      taken together, or of mild deformities. However, in aggregate these conditions
      were associated with a 2.3-fold increase (95% 1.1-4.8) in very severe vertebral
      deformities, which points to a role for rapid cancellous bone loss among women
      with the worst spinal osteoporosis.

PMID- 9916785
TI  - Regional differences in cortical porosity in the fractured femoral neck.
AB  - Although bone mass is a contributory risk factor for intracapsular hip fracture,
      its distribution and porosity within the femoral neck is also important for bone
      strength. In femoral neck biopsies from 13 women with intracapsular hip fracture
      (mean +/- SEM: 75.4+/-2.1 years, OP) and 19 cadaveric samples (9 men and 10 women
      [control], aged 79.4+/-1.7 years), a segmental analysis was used to quantify
      circumferential variations in the characteristics of cortical bone haversian
      systems. In female control femoral necks, there was an increasing porosity
      gradient between the inferior (I) (7.7+/-0.6%) and superior regions (S) (16.05+/
      1.8%,p < 0.005). In walking, these regions undergo compression and tension,
      respectively. In men, a similar trend was observed, but the differences were not
      significant (I: 11.1+/-1.2%; S: 14.1+/-1.7%; p = 0.133). This porosity gradient
      was not maintained in the fracture group (I: 10+/-1%; S: 12.65+/-1.2%). In
      contrast, porosity in the fracture group was greatest in the anterior cortex,
      being 41% higher in that quadrant than in controls (p = 0.06). The areal density
      of haversian canals ranged from 16.7 to 21.3 canals/mm2 with no significant
      differences between fractures and controls. In the control women, mean canal
      diameter was highest in the superior region (60+/-2.8 microm), and these canals
      were significantly larger than those in the inferior region (49.4+/-1.4 microm, p
      < 0.05). This difference was less marked in the fracture cases (I: 53.21+/-2.5
      microm; S: 59.1+/-2.8 microm; p = 0.0878). Although the mean canal diameter in
      the anterior quadrant of the fracture cases was higher than in the control women
      this did not reach significance (OP/F: 59.5+/-3 microm; control/F: 52.7+/-2.6
      microm; p = 0.106). However, the proportion of "giant" canals with diameters >385
      microm (defined as the top 0.5% in the controls) was doubled in the anterior
      region of the fracture cases (OP/F: 1.28%; control/F: 0.69%; p < 0.005). Porosity
      is related to the square of the canal radius; therefore, such canals make a
      substantial contribution to cortical porosity. Previous work has shown that the
      elastic modulus of bone decreases approximately as the square root of porosity.
      Therefore, the increased porosity and the higher prevalence of "giant" canals
      have a markedly negative influence on the ability of the cortical shell to
      withstand stresses associated with a fall. The mechanisms responsible for the
      localized generation of "giant" haversian canals, and ultimately the
      "trabecularization" of the cortex, require further investigation.

PMID- 9916787
TI  - The chip challenge.

PMID- 9916788
TI  - Hershey heaven and Caenorhabditis elegans.

PMID- 9916786
TI  - Alendronate increases spine and hip bone mineral density in women with
      postmenopausal osteoporosis who failed to respond to intermittent cyclical
      etidronate.
AB  - In a U.S. multicenter study of intermittent cyclical etidronate treatment for
      postmenopausal osteoporosis, approximately 20% of patients were nonresponders,
      defined as failure to increase spine bone mineral density. In contrast,
      essentially all patients who received 10 mg of alendronate daily in U.S. phase
      III trials showed some increase in spine bone mineral density. The current study
      was undertaken to determine the response to alendronate therapy in women with
      postmenopausal osteoporosis who were nonresponders to intermittent cyclical
      etidronate therapy. Twenty-five women with postmenopausal osteoporosis (mean +/-
      SD: 65.1+/-1.9 years of age), previously treated with intermittent cyclical
      etidronate with no increase of spine bone mineral density, and who agreed to be
      changed to alendronate, were recruited from a university out-patient clinic
      specializing in the treatment of osteoporosis for a prospective observational
      study. Measurements included bone mineral density of the lumbar spine and
      proximal femur (by dual-energy X-ray absorptiometry) and biochemical markers of
      bone remodeling (serum bone-specific alkaline phosphatase by immunoassay and
      urine deoxypyridinoline by high-pressure liquid chromatography). Patients had
      received intermittent cyclical etidronate for 3.3+/-0.4 years, during which time
      their bone density declined at spine and hip sites. They were then changed to
      alendronate 10 mg/day, which they received for 1.3+/-0.1 years; after treatment
      with alendronate, bone mineral density increased significantly at the lumbar
      spine (4.4+/-0.7% annualized,p < 0.0001) and at all hip sites. Bone markers also
      changed significantly after alendronate treatment: urine deoxypyridinoline fell
      from 6.8+/-0.8 to 5.5+/-0.6 micromol/mol creatinine (p < 0.0001) and serum bone
      specific alkaline phosphatase rose from 4.6+/-0.5 to 11.9+/-1.0 ng/mL (p <
      0.0001). Upper gastrointestinal side effects forced 4 of 25 patients (16%) to
      discontinue alendronate. Alendronate increases bone density at the spine and hip
      in patients who have not responded to intermittent cyclical etidronate therapy.
      Changes in bone markers suggest that alendronate causes more complete suppression
      of bone resorption and less inhibition (or stimulation) of bone formation.

PMID- 9916789
TI  - A molecular blueprint for targeting cancer?

PMID- 9916790
TI  - Making family trees from gene families.

PMID- 9916791
TI  - Kidney kinetics and chloride ion pumps.

PMID- 9916792
TI  - Generalized lacZ expression with the ROSA26 Cre reporter strain.

PMID- 9916793
TI  - Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer
      disease.

PMID- 9916794
TI  - An action plan for mouse genomics.
AB  - The mouse has become the leading animal model for studying biological processes
      in mammals. Creation of additional genomic and genetic resources will make the
      mouse an even more useful model for the research community. On the basis of
      recommendations from the scientific community, the National Institutes of Health
      (NIH) plans to support grants to generate a 'working draft' sequence of the mouse
      genome by 2003, systematic mutagenesis and phenotyping centres, repositories for
      mouse strain maintenance, distribution and cryopreservation and training
      fellowships in mouse pathobiology.

PMID- 9916795
TI  - Identification of Cd36 (Fat) as an insulin-resistance gene causing defective
      fatty acid and glucose metabolism in hypertensive rats.
AB  - The human insulin-resistance syndromes, type 2 diabetes, obesity, combined
      hyperlipidaemia and essential hypertension, are complex disorders whose genetic
      basis is unknown. The spontaneously hypertensive rat (SHR) is insulin resistant
      and a model of these human syndromes. Quantitative trait loci (QTLs) for SHR
      defects in glucose and fatty acid metabolism, hypertriglyceridaemia and
      hypertension map to a single locus on rat chromosome 4. Here we combine use of
      cDNA microarrays, congenic mapping and radiation hybrid (RH) mapping to identify
      a defective SHR gene, Cd36 (also known as Fat, as it encodes fatty acid
      translocase), at the peak of linkage to these QTLs. SHR Cd36 cDNA contains
      multiple sequence variants, caused by unequal genomic recombination of a
      duplicated ancestral gene. The encoded protein product is undetectable in SHR
      adipocyte plasma membrane. Transgenic mice overexpressing Cd36 have reduced blood
      lipids. We conclude that Cd36 deficiency underlies insulin resistance, defective
      fatty acid metabolism and hypertriglyceridaemia in SHR and may be important in
      the pathogenesis of human insulin-resistance syndromes.

PMID- 9916796
TI  - Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular
      acidosis with sensorineural deafness.
AB  - H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an
      electrochemical gradient, whereas F-ATPases reverse the process, synthesizing
      ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the
      apical proton pump mediating distal nephron acid secretion, cause distal renal
      tubular acidosis, a condition characterized by impaired renal acid secretion
      resulting in metabolic acidosis. Patients with ATP6B1 mutations also have
      sensorineural hearing loss; consistent with this finding, we demonstrate
      expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with
      the known requirement for active proton secretion to maintain proper endolymph
      pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function.
      ATP6B1 is the first member of the H+-ATPase gene family in which mutations are
      shown to cause human disease.

PMID- 9916797
TI  - Primary systemic carnitine deficiency is caused by mutations in a gene encoding
      sodium ion-dependent carnitine transporter.
AB  - Primary systemic carnitine deficiency (SCD; OMIM 212140) is an autosomal
      recessive disorder characterized by progressive cardiomyopathy, skeletal
      myopathy, hypoglycaemia and hyperammonaemia. SCD has also been linked to sudden
      infant death syndrome. Membrane-physiological studies have suggested a defect of
      the carnitine transport system in the plasma membrane in SCD patients and in the
      mouse model, juvenile visceral steatosis. Although the responsible loci have been
      mapped in both human and mouse, the underlying gene has not yet been identified.
      Recently, we cloned and analysed the function of a novel transporter protein
      termed OCTN2. Our observation that OCTN2 has the ability to transport carnitine
      in a sodium-dependent manner prompted us to search for mutations in the gene
      encoding OCTN2, SLC22A5. Initially, we analysed the mouse gene and found a
      missense mutation in Slc22a5 in jvs mice. Biochemical analysis revealed that this
      mutation abrogates carnitine transport. Subsequent analysis of the human gene
      identified four mutations in three SCD pedigrees. Affected individuals in one
      family were homozygous for the deletion of a 113-bp region containing the start
      codon. In the second pedigree, the affected individual was shown to be a compound
      heterozygote for two mutations that cause a frameshift and a premature stop
      codon, respectively. In an affected individual belonging to a third family, we
      found a homozygous splice-site mutation also resulting in a premature stop codon.
      These mutations provide the first evidence that loss of OCTN2 function causes
      SCD.

PMID- 9916798
TI  - Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel.
AB  - CLC-K1 is a kidney-specific chloride channel that mediates transepithelial
      chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner
      medulla. Transport of NaCl in the tAL is thought to be a component of urinary
      concentration in a passive model of the countercurrent multiplication system, but
      there has been no direct evidence that CLC-K1 is involved in urine concentration.
      To analyse the physiological function of CLC-K1 in vivo, we generated mice
      lacking CLC-K1 by targeted gene disruption. Clcnk1-/- mice were physically normal
      appearance, but produced approximately five times more urine than Clcnk1+/- and
      Clcnk1+/+ mice. After 24 hours of water deprivation, Clcnk1-/- mice were severely
      dehydrated and lethargic, with a decrease of approximately 27% in body weight.
      Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin
      (dDAVP) induced a threefold increase in urine osmolarity in Clcnk1+/- and
      Clcnk1+/+ mice, whereas only a minimal increase was seen in Clcnk1-/- mice,
      indicating nephrogenic diabetes insipidus. After in vitro perfusion of the tAL,
      the lumen-to-bath chloride gradient did not produce a diffusion potential in
      Clcnk1-/- mice in contrast to Clcnk1+/+ and Clcnk1+/- mice. These results
      establish that CLC-K1 has a role in urine concentration, and that the
      countercurrent system in the inner medulla is involved in the generation and
      maintenance of hypertonic medullary interstitium.

PMID- 9916799
TI  - PIK3CA is implicated as an oncogene in ovarian cancer.
AB  - Ovarian cancer is the leading cause of death from gynecological malignancy and
      the fourth leading cause of cancer death among American women, yet little is
      known about its molecular aetiology. Studies using comparative genomic
      hybridization (CGH) have revealed several regions of recurrent, abnormal, DNA
      sequence copy number that may encode genes involved in the genesis or progression
      of the disease. One region at 3q26 found to be increased in copy number in
      approximately 40% of ovarian and others cancers contains PIK3CA, which encodes
      the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3-kinase).
      The association between PIK3CA copy number and PI3-kinase activity makes PIK3CA a
      candidate oncogene because a broad range of cancer-related functions have been
      associated with PI3-kinase mediated signalling. These include proliferation,
      glucose transport and catabolism, cell adhesion, apoptosis, RAS signalling and
      oncogenic transformation. In addition, downstream effectors of PI3-kinase, AKT1
      and AKT2, have been found to be amplified or activated in human tumours,
      including ovarian cancer. We show here that PIK3CA is frequently increased in
      copy number in ovarian cancers, that the increased copy number is associated with
      increased PIK3CA transcription, p110alpha protein expression and PI3-kinase
      activity and that treatment with the PI3-kinase inhibitor LY294002 decreases
      proliferation and increases apoptosis. Our observations suggest PIK3CA is an
      oncogene that has an important role in ovarian cancer.

PMID- 9916800
TI  - Synergy of demethylation and histone deacetylase inhibition in the re-expression
      of genes silenced in cancer.
AB  - Densely methylated DNA associates with transcriptionally repressive chromatin
      characterized by the presence of underacetylated histones. Recently, these two
      epigenetic processes have been dynamically linked. The methyl-CpG-binding protein
      MeCP2 appears to reside in a complex with histone deacetylase activity. MeCP2 can
      mediate formation of transcriptionally repressive chromatin on methylated
      promoter templates in vitro, and this process can be reversed by trichostatin A
      (TSA), a specific inhibitor of histone deacetylase. Little is known, however,
      about the relative roles of methylation and histone deacetylase activity in the
      stable inhibition of transcription on densely methylated endogenous promoters,
      such as those for silenced alleles of imprinted genes, genes on the female
      inactive X chromosome and tumour-suppressor genes inactivated in cancer cells. We
      show here that the hypermethylated genes MLH1, TIMP3 (TIMP3), CDKN2B (INK4B, p15)
      and CDKN2A (INK4, p16) cannot be transcriptionally reactivated with TSA alone in
      tumour cells in which we have shown that TSA alone can upregulate the expression
      of non-methylated genes. Following minimal demethylation and slight gene
      reactivation in the presence of low dose 5-aza-2'deoxycytidine (5Aza-dC),
      however, TSA treatment results in robust re-expression of each gene. TSA does not
      contribute to demethylation of the genes, and none of the treatments alter the
      chromatin structure associated with the hypermethylated promoters. Thus, although
      DNA methylation and histone deacetylation appear to act as synergistic layers for
      the silencing of genes in cancer, dense CpG island methylation is dominant for
      the stable maintenance of a silent state at these loci.

PMID- 9916801
TI  - Genome phylogeny based on gene content.
AB  - Species phylogenies derived from comparisons of single genes are rarely
      consistent with each other, due to horizontal gene transfer, unrecognized
      paralogy and highly variable rates of evolution. The advent of completely
      sequenced genomes allows the construction of a phylogeny that is less sensitive
      to such inconsistencies and more representative of whole-genomes than are single
      gene trees. Here, we present a distance-based phylogeny constructed on the basis
      of gene content, rather than on sequence identity, of 13 completely sequenced
      genomes of unicellular species. The similarity between two species is defined as
      the number of genes that they have in common divided by their total number of
      genes. In this type of phylogenetic analysis, evolutionary distance can be
      interpreted in terms of evolutionary events such as the acquisition and loss of
      genes, whereas the underlying properties (the gene content) can be interpreted in
      terms of function. As such, it takes a position intermediate to phylogenies based
      on single genes and phylogenies based on phenotypic characteristics. Although our
      comprehensive genome phylogeny is independent of phylogenies based on the level
      of sequence identity of individual genes, it correlates with the standard
      reference of prokarytic phylogeny based on sequence similarity of 16s rRNA. Thus,
      shared gene content between genomes is quantitatively determined by phylogeny,
      rather than by phenotype, and horizontal gene transfer has only a limited role in
      determining the gene content of genomes.

PMID- 9916802
TI  - Telomerase expression in human somatic cells does not induce changes associated
      with a transformed phenotype.
AB  - Expression of the human telomerase catalytic component, hTERT, in normal human
      somatic cells can reconstitute telomerase activity and extend their replicative
      lifespan. We report here that at twice the normal number of population doublings,
      telomerase-expressing human skin fibroblasts (BJ-hTERT) and retinal pigment
      epithelial cells (RPE-hTERT) retain normal growth control in response to serum
      deprivation, high cell density, G1 or G2 phase blockers and spindle inhibitors.
      In addition, we observed no cell growth in soft agar and detected no tumour
      formation in vivo. Thus, we find that telomerase expression in normal cells does
      not appear to induce changes associated with a malignant phenotype.

PMID- 9916803
TI  - Absence of cancer-associated changes in human fibroblasts immortalized with
      telomerase.
AB  - The ectopic expression of telomerase in normal human cells results in an extended
      lifespan, indicating that telomere shortening regulates the timing of cellular
      senescence. As telomerase expression is a hallmark of cancer, we investigated the
      long-term effects of forced expression of human telomerase catalytic component
      (hTERT) in normal human fibroblasts. In vitro growth requirements, cell-cycle
      checkpoints and karyotypic stability in telomerase-expressing cells are similar
      to those of untransfected controls. In addition, co-expression of telomerase, the
      viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS
      does not result in growth in soft agar. Thus, although ectopic expression of
      telomerase in human fibroblasts is sufficient for immortalization, it does not
      result in changes typically associated with malignant transformation.

PMID- 9916804
TI  - Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic
      peptides.
AB  - Mutations reducing the functional activity of leptin, the leptin receptor, alpha
      melanocyte stimulating hormones (alpha-MSH) and the melanocortin-4 receptor
      (Mc4r) all lead to obesity in mammals. Moreover, mutant mice that ectopically
      express either agouti (Ay/a mice) or agouti-related protein (Agrp), antagonists
      of melanocortin signalling, become obese. These data suggest that alpha-MSH
      signalling transduced by Mc4r tonically inhibits feeding; however, it is not
      known to what extent this pathway mediates leptin signalling. We show here that
      Mc4r-deficient (Mc4r-/-) mice do not respond to the anorectic actions of MTII, an
      MSH-like agonist, suggesting that alpha-MSH inhibits feeding primarily by
      activating Mc4r. Obese Mc4r-/-mice do not respond significantly to the inhibitory
      effects of leptin on feeding, whereas non-obese Mc4r-/- mice do. These data
      demonstrate that melanocortin signalling transduced by Mc4r is not an exclusive
      target of leptin action and that factors resulting from obesity contribute to
      leptin resistance. Leptin resistance of obese Mc4r-/- mice does not prevent their
      response to the anorectic actions of ciliary neurotrophic factor (CNTF),
      corticotropin releasing factor (CRF), or urocortin; or the orexigenic actions of
      neuropeptide Y (NPY) or peptide YY (PYY), indicating that these neuromodulators
      act independently or downstream of Mc4r signalling.

PMID- 9916806
TI  - Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and
      predisposes to melanoma.
AB  - Approximately 8-12% of melanoma is inherited in an autosomal dominant fashion
      with variable penetrance. A chromosome 9p21 locus has been linked to this disease
      in 50-80% of affected families. CDKN2A (also known as P16, INK4, p16INK4A and
      MTS1) is allelic to this locus and encodes a cdk4/cdk6 kinase inhibitor that
      constrains cells from progressing through the G1 restriction point. Although
      germline CDKN2A coding mutations cosegregate with melanoma in 25-60% of families
      predisposed to the disease, there remains a number of mutation-negative families
      that demonstrate linkage of inherited melanoma to 9p21 markers. We show here that
      a subset of these kindreds possess a G-->T transversion at base -34 of CDKN2A,
      designated G-34T. This mutation gives rise to a novel AUG translation initiation
      codon that decreases translation from the wild-type AUG. The G-34T mutation is
      not seen in controls, segregates with melanoma in families and, on the basis of
      haplotyping studies, probably arose from a common founder in the United Kingdom.
      Characterization of this and other CDKN2A non-coding mutations should have an
      impact on current efforts to identify susceptible melanoma-prone families and
      individuals.

PMID- 9916805
TI  - Mammalian MutS homologue 5 is required for chromosome pairing in meiosis.
AB  - MSH5 (MutS homologue 5) is a member of a family of proteins known to be involved
      in DNA mismatch repair. Germline mutations in MSH2, MLH1 and GTBP (also known as
      MSH6) cause hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome.
      Inactivation of Msh2, Mlh1, Gtmbp (also known as Msh6) or Pms2 in mice leads to
      hereditary predisposition to intestinal and other cancers. Early studies in yeast
      revealed a role for some of these proteins, including Msh5, in meiosis. Gene
      targeting studies in mice confirmed roles for Mlh1 and Pms2 in mammalian meiosis.
      To assess the role of Msh5 in mammals, we generated and characterized mice with a
      null mutation in Msh5. Msh5-/- mice are viable but sterile. Meiosis in these mice
      is affected due to the disruption of chromosome pairing in prophase I. We found
      that this meiotic failure leads to a diminution in testicular size and a complete
      loss of ovarian structures. Our results show that normal Msh5 function is
      essential for meiotic progression and, in females, gonadal maintenance.

PMID- 9916807
TI  - Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart
      specific inactivation of mitochondrial DNA gene expression.
AB  - Mutations of mitochondrial DNA (mtDNA) cause several well-recognized human
      genetic syndromes with deficient oxidative phosphorylation and may also have a
      role in ageing and acquired diseases of old age. We report here that hallmarks of
      mtDNA mutation disorders can be reproduced in the mouse using a conditional
      mutation strategy to manipulate the expression of the gene encoding mitochondrial
      transcription factor A (Tfam, previously named mtTFA), which regulates
      transcription and replication of mtDNA. Using a loxP-flanked Tfam allele
      (TfamloxP) in combination with a cre-recombinase transgene under control of the
      muscle creatinine kinase promoter, we have disrupted Tfam in heart and muscle.
      Mutant animals develop a mosaic cardiac-specific progressive respiratory chain
      deficiency, dilated cardiomyopathy, atrioventricular heart conduction blocks and
      die at 2-4 weeks of age. This animal model reproduces biochemical, morphological
      and physiological features of the dilated cardiomyopathy of Kearns-Sayre
      syndrome. Furthermore, our findings provide genetic evidence that the respiratory
      chain is critical for normal heart function.

PMID- 9916809
TI  - Mutations in the gene encoding the human matrix Gla protein cause Keutel
      syndrome.
AB  - Keutel syndrome (KS, MIM 245150) is an autosomal recessive disorder characterized
      by abnormal cartilage calcification, peripheral pulmonary stenosis and midfacial
      hypoplasia. A genome search using homozygosity mapping provided evidence of
      linkage to chromosome 12p12.3-13.1 (maximum multipoint lod score, 4.06). MGP was
      a candidate on the basis of its localization to this chromosomal region and the
      known function of its protein. MGP maps to chromosome 12p near D12S363. Human MGP
      is a 10-kD skeletal extracellular matrix (ECM) protein that consists of an 84-aa
      mature protein and a 19-aa transmembrane signal peptide. It is a member of the
      Gla protein family, which includes osteocalcin, another skeletal ECM protein, and
      a number of coagulation factors (factors II, VII, IX, X and proteins S and C).
      All members of this family have glutamic acid residues modified to gamma
      carboxyglutamic acids (Gla) by a specific gamma-carboxylase using vitamin K as a
      cofactor. The modified glutamic acid residues of Gla proteins confer a high
      affinity for mineral ions such as calcium, phosphate and hydroxyapatite crystals,
      the mineral components of the skeletal ECM. The pattern and tissue distribution
      of Mgp expression in mice suggest a role for Mgp in regulating ECM calcification.
      Mglap-deficient mice (Mglap-/-) have been reported to have inappropriate
      calcification of cartilage. Mutational analysis of MGP in three unrelated
      probands identified three different mutations: c.69delG, IVS1-2A-->G and c.113T-
      >A. All three mutations predict a non-functional MGP. Our data indicate that
      mutations in MGP are responsible for KS and confirm its role in the regulation of
      extracellular matrix calcification.

PMID- 9916808
TI  - Fgf10 is essential for limb and lung formation.
AB  - The interactions between fibroblast growth factors (FGF) and their receptors have
      important roles in mediating mesenchymal-epithelial cell interactions during
      embryogenesis. In particular, Fgf10 is predicted to function as a regulator of
      brain, lung and limb development on the basis of its spatiotemporal expression
      pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10
      deficient mice. Fgf10-/- mice died at birth due to the lack of lung development.
      Trachea was formed, but subsequent pulmonary branching morphogenesis was
      disrupted. In addition, mutant mice had complete truncation of the fore- and
      hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of
      the limb buds did not occur; however, formation of the clavicles was not
      affected. Analysis of the expression of marker genes in the mutant limb buds
      indicated that the apical ectodermal ridge (AER) and the zone of polarizing
      activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential
      regulator of lung and limb formation.

PMID- 9916810
TI  - New work times are here--are we ready?

PMID- 9916811
TI  - International regulations on the organization of shift work.
AB  - Changes since the early 1990s in international regulations on night and shift
      work were reviewed, including changes in complex shift systems, greater
      flexibility, increased female participation in night work and attention to health
      effects. Recent international regulations have focused on (i) a broadened scope
      of regulatory measures treating both genders equally, (ii) multifaceted
      protection, and (iii) consultation weighing many aspects of job design. The
      application of these international regulations depends on national laws and
      practice, with possible derogations. It calls for local support measures,
      including (i) guidelines for enterprise-level consultations on shift schedules,
      (ii) promotion of health and safety measures, and (iii) participatory strategies
      for locally adjusted shiftwork arrangements and social support.

PMID- 9916812
TI  - Innovative worktime arrangements.
AB  - New worktime models can be introduced from an employer's point of view for many
      reasons. They can extend operational time for better utilization of expensive
      equipment, provide customer-oriented service hours, adjust operational time to
      the varying needs of personnel, adhere to a given operational time despite a
      reduction in workhours, avoid dismissals, or improve job attractiveness for
      qualified personnel. On the other hand, there are also many reasons for changing
      traditional worktime models from an employee's point of view. For example, new
      models can help fit private needs to occupational demands, change worktime
      according to life's phases, provide more autonomy for the organization of
      worktime or the choice of worktime model, and allow for reduced capacity due to
      illness or age. The paper primarily presents examples of innovative worktime
      models (eg, annual worktime, time-autonomous group, variable worktime, choice
      between different worktime models) but also discusses the possible negative
      effects of new worktime arrangements.

PMID- 9916813
TI  - Is there an optimal sleep-wake pattern in shift work?
AB  - This paper finds that shift work clearly affects sleep and wakefulness but that
      there is very little known empirically about optimal sleep-wake patterns--except
      for the ones commonly used but not evaluated, for example, extension of morning
      sleep after night work, split sleep (main sleep + nap), nap positioning and
      duration, delay of main sleep, full commitment to night work (including bright
      light), phase advance and napping in relation to morning work, and modification
      of sleep strategies depending on the speed and direction of rotation. Thus
      computer simulations of the efficacy of alternative strategies must sometimes be
      used. The paper tries several such approaches and finds some possible ways of
      optimizing sleep. Still, the need for empirical data is emphasized.

PMID- 9916814
TI  - Shift work and reproductive health.
AB  - Nonstandard workhours may disturb normal body functions, but their relation to
      reproductive outcome is poorly understood. Two newly published studies suggest an
      association between rotating shift work and prolonged waiting time to pregnancy.
      Seven of nine studies on spontaneous abortion suggest that some forms of shift
      work may be associated with increased risk. Four studies indicate that shift work
      including night schedules may be related to preterm birth. Moreover, some results
      have related rotating schedules to intrauterine growth retardation. In the
      published studies, the type of work schedule examined has varied, and the applied
      definition of shift work has not necessarily been clear. The main interest areas,
      however, have been work involving evening and night shifts, rotating or changing
      schedules, and the irregularity of work patterns. Although the evidence is not
      ample and remains ambiguous, it is prudent to consider shift work as a potential
      risk to reproduction.

PMID- 9916815
TI  - Individual and social determinants of shiftwork tolerance.
AB  - This paper reviews evidence published on individual and social determinants of
      shiftwork tolerance since 1993. In agreement with earlier reviews, individual
      differences show only some low and inconsistent concurrent covariation with
      shiftwork tolerance, and no predictive power for these measures has been found.
      It is thus not possible to predict future shiftwork tolerance from individual
      differences. Social conditions are also related to shiftwork tolerance, although
      again predictive power has not been demonstrated. An examination of the reasons
      for this state of the art suggested means of improving the relevance and
      usability of future research in this area.

PMID- 9916816
TI  - Accident risk as a function of hour at work and time of day as determined from
      accident data and exposure models for the German working population.
AB  - OBJECTIVES: Recent studies indicate that accident risk may be a function of hour
      at work and time of day. Further evidence was sought for these assumptions, along
      with the answer to the question of whether the risk of accident can be conceived
      as an interaction between hours at work and time of day. METHODS: Data on more
      than 1.2 million accidents for the year 1994 were provided, all listed according
      to the time of day and hour at work. Since information about how long each day
      and at what time of day people work is not available in Germany, different
      exposure models had to be estimated. For estimating the risk of having an
      accident relative accident risks were calculated from the ratio of accident
      frequencies to the exposure data. RESULTS: An exponentially increasing accident
      risk was observed beyond the 9th hour at work. The relative accident risks
      differed considerably according to the respective exposure model with regard to
      time of day. A highly significant interaction effect was found for hour at work
      by time of day, the percentage of accidents at different hours at work varying
      according to the particular time of day when work is started. For the 3
      "traditional" shiftwork starting times, it was shown that, with later starting
      times, the relative accident risk increased dramatically beyond the 8th hour at
      work. CONCLUSIONS: Since the results clearly indicate that there are time-related
      effects on occupational accident risk, more detailed analyses are called for.
      More elaborated exposure models should be used to assess the efficiency of work
      schedules with extended workhours, especially under shiftwork conditions. The
      results also indicate the necessity of recording and providing adequate data
      bases for such analyses.

PMID- 9916817
TI  - Shift length as a determinant of retrospective on-shift alertness.
AB  - OBJECTIVES: This study examined the combined effects of shift length (8 versus 12
      hours) and night-to-morning-shift changeover time (0600 versus 0700) on
      retrospective on-shift alertness ratings. METHODS: An abridged version of the
      Standard Shiftwork Index, which included retrospective alertness ratings, was
      completed by 4 groups of industrial shift workers. Two groups worked 8-hour shift
      systems and started their morning shifts at either 0600 or 0700; the other 2
      groups worked 12-hour systems, starting their day shifts at either 0600 or 0700.
      RESULTS: The 8-hour workers reported considerably higher levels of alertness in
      the afternoon, while the 12-hour workers were more alert than the 8-hour workers
      in the morning and at 2200. Workers who started their shift around 0600 were less
      alert during the morning than those who started around 0700. The data suggested
      that the combined effects of working 8-hour shifts and starting the morning shift
      at around 0600 have particularly deleterious effects upon alertness. CONCLUSIONS:
      Effects on alertness can be explained in terms of differences in elapsed time on
      duty, sleep duration, sleep disruption, and chronic fatigue. The findings of this
      study appear to contradict previous research demonstrating that the major
      deleterious effects of extended shifts and delayed changeovers upon alertness
      occur at night. However, it is acknowledged that the absence of a difference in
      alertness at night may have been due to floor effects. Nevertheless, the
      implications of the alertness ratings for performance and safety, particularly
      during the afternoon, should not be ignored.

PMID- 9916818
TI  - Change from slowly rotating 8-hour shifts to rapidly rotating 8-hour and 12-hour
      shifts using participative shift roster design.
AB  - OBJECTIVES: The study examined the impact of change, from slowly rotating
      continuous 8-hour shifts to more rapidly rotating continuous 8-hour and 12-hour
      shifts, on the health and quality of life of shift workers. METHODS: Self-report
      survey data were collected from 72 shift workers at 3 sewage treatment plants
      before and several months after roster change. After the change 1 plant first
      worked a rapidly rotating, 8-hour shift roster and then worked a 12-hour shift
      roster, and the other 2 plants worked continuous 12-hour shift rosters. RESULTS:
      After the change the shift workers at each plant reported increased satisfaction
      with roster design, a decrease in physical and psychological circadian malaise
      associated with shift work, improved day sleep quality, less tiredness, and
      improvements in the quality of home, social and work life. A between-plant
      comparison of the rapidly rotating 8-hour and 12-hour shift rosters showed
      greater improvements had been obtained with the 12-hour shift roster, and no
      significant differences in tiredness or sleep quality between the redesigned 8-
      and 12-hour shift rosters. However, a within-plant matched-pairs comparison at
      the 1st plant of the rapidly rotating 8-hour shift roster and the 12-hour shift
      roster showed no significant differences. CONCLUSIONS: The results show that the
      prior level of support for change may best explain the impact of roster redesign
      on individual well-being. They lend further support to shift worker participation
      in roster design.

PMID- 9916819
TI  - Effects of alternating 8- and 12-hour shifts on sleep, sleepiness, physical
      effort and performance.
AB  - OBJECTIVES: The aim of the present study was to compare 12-hour shifts during
      weekends with 8-hour shifts during weekdays with respect to sleep, sleepiness,
      physical effort, and performance. METHODS: Thirty-one subjects at a power plant
      participated. Sleep, sleepiness, and physical effort were measured with a diary.
      About half of the subjects carried out a reaction-time test during both 8- and 12
      hour morning and night shifts. The remaining subjects carried out a vigilance
      task. RESULTS: Sleepiness was higher and physical effort lower on the 12-hour
      night shift than on the 8-hour night shift. However, the subjects who had the
      same level of physical effort on 8- and 12-hour night shifts did not differ with
      respect to sleepiness. During the 12-hour morning shift, sleepiness was lower and
      the sleep length was longer than on the 8-h morning shift. The subjects who had
      the same amount of sleep for 8- and 12-hour morning shifts showed no difference
      in sleepiness. Sleep did not differ between 8- and 12-hour night shifts. There
      was no difference between 8- and 12-hour shifts with respect to performance.
      CONCLUSIONS: It was suggested that the difference in sleepiness between 8- and 12
      hour shifts is related to differences in sleep length for the morning shift, and
      to differences in physical effort for the night shift, rather than to shift
      duration. Thus the most likely conclusion is that 12-hour shifts do not cause
      increased sleepiness or impaired performance or disturbed sleep.

PMID- 9916820
TI  - Change from an 8-hour shift to a 12-hour shift, attitudes, sleep, sleepiness and
      performance.
AB  - OBJECTIVES: The present study sought to evaluate the effect of a change from a
      rotating 3-shift (8-hour) to a 2-shift shift (12 hour) schedule on sleep,
      sleepiness, performance, perceived health, and well-being. METHODS: Thirty-two
      shift workers at a chemical plant (control room operators) responded to a
      questionnaire a few months before a change was made in their shift schedule and
      10 months after the change. Fourteen workers also filled out a diary, carried
      activity loggers, and carried out reaction-time tests (beginning and end of
      shift). Fourteen day workers served as a reference group for the questionnaires
      and 9 were intensively studied during a week with workdays and a free weekend.
      RESULTS: The questionnaire data showed that the shift change increased
      satisfaction with workhours, sleep, and time for social activities. Health,
      perceived accident risk, and reaction-time performance were not negatively
      affected. Alertness improved and subjective recovery time after night work
      decreased. The quick changes in the 8-hour schedule greatly increased sleep
      problems and fatigue. Sleepiness integrated across the entire shift cycle showed
      that the shift workers were less alert than the day workers, across workdays and
      days off (although alertness increased with the 12-hour shift). CONCLUSIONS: The
      change from 8-hour to 12-hour shifts was positive in most respects, possibly due
      to the shorter sequences of the workdays, the longer sequences of consecutive
      days off, the fewer types of shifts (easier planning), and the elimination of
      quick changes. The results may differ in groups with a higher work load.

PMID- 9916822
TI  - Management of health and safety in the organization of worktime at the local
      level.
AB  - OBJECTIVES: This study examined the consideration of health and safety issues in
      the local process of organizing worktime within the framework of regulations.
      METHODS: The study encompassed all 7 hospitals in one region of Denmark. Twenty
      three semi-structured interviews were carried out with 2 representatives from the
      different parties involved (management, cooperation committees, health and safety
      committees from each hospital, and 2 local unions). Furthermore, a questionnaire
      was sent to all 114 wards with day and night duty. The response rate was 84%.
      Data were collected on alterations in worktime schedules, responsibilities,
      reasons for the present design of schedules, and use of inspection reports.
      RESULTS: The organization of worktime takes place in single wards without
      external interference and without guidelines other than the minimum standards set
      in regulations. At the ward level, management and employees were united in a
      mutual desire for flexibility, despite the fact that regulations were not always
      followed. No interaction was found in the management of health and safety factors
      between the parties concerned at different levels. CONCLUSIONS: The demands for
      flexibility in combination with the absence of guidelines and the missing
      dynamics between the parties involved imply that the handling of health and
      safety issues in the organization of worktime may be accidental and unsystematic.
      In order to consider the health and safety of night and shift workers within the
      framework of regulations, a clarification of responsibilities, operational
      levels, and cooperation is required between the parties concerned.

PMID- 9916821
TI  - Subjective alertness and sleep quality in connection with permanent 12-hour day
      and night shifts.
AB  - OBJECTIVES: The aim of this study was to compare permanent 12-hour day and night
      shifts (shift change over times at 0500 and 1700) in a shift system with 3 work
      periods followed by 4 free days. METHODS: Sleep diaries were collected after main
      periods of sleep, and sleepiness ratings [Karolinska sleepiness scale (KSS)] were
      obtained 4 times during the last free day and also during the following 3
      workshifts. Eighteen to twenty night workers and 8-10 day workers (depending on
      the instrument) participated. RESULTS: The day workers were significantly
      sleepier during their workdays. Times for going to bed and for rising differed
      between the groups. The amount of sleep per week did not differ between groups,
      but the pattern across days did in that the day workers had a short sleep (5
      hours) before the first day and 6 hours of sleep after the other two. Night
      workers slept long (9 hours) before the first shift and had 6.5-hour sleep
      periods after the other shifts. During free time the day workers slept around 9
      hours and the night workers around 8 hours. Sleep quality and ease of awakening
      showed no group differences in overall levels, but the day workers had
      difficulties awakening before their shifts. The night workers had little
      variation in sleep quality or difficulties awakening. CONCLUSIONS: The suggested
      explanation for the greater sleepiness and difficulties awakening among the day
      workers was the early start of the shift and the difficulties the workers had
      with phase advancing their sleep-wake rhythm.

PMID- 9916823
TI  - Knowledge-based support for the participatory design and implementation of shift
      systems.
AB  - OBJECTIVES: This study developed a knowledge-based software system to support the
      participatory design and implementation of shift systems as a joint planning
      process including shift workers, the workers' committee, and management. METHODS:
      The system was developed using a model-based approach. During the 1st phase,
      group discussions were repeatedly conducted with 2 experts. Thereafter a
      structure model of the process was generated and subsequently refined by the
      experts in additional semistructured interviews. Next, a factual knowledge base
      of 1713 relevant studies was collected on the effects of shift work. Finally, a
      prototype of the knowledge-based system was tested on 12 case studies. RESULTS:
      During the first 2 phases of the system, important basic information about the
      tasks to be carried out is provided for the user. During the 3rd phase this
      approach uses the problem-solving method of case-based reasoning to determine a
      shift rota which has already proved successful in other applications. It can then
      be modified in the 4th phase according to the shift workers' preferences. The
      last 2 phases support the final testing and evaluation of the system. The
      application of this system has shown that it is possible to obtain shift rotas
      suitable to actual problems and representative of good ergonomic solutions.
      CONCLUSIONS: A knowledge-based approach seems to provide valuable support for the
      complex task of designing and implementing a new shift system. The separation of
      the task into several phases, the provision of information at all stages, and the
      integration of all parties concerned seem to be essential factors for the success
      of the application.

PMID- 9916824
TI  - The significance of rota representation in the design of rotas.
AB  - Shift scheduling is based on some representation of shift schedules. The number
      of different representations currently used is high, and one might expect small
      practical differences between these representations. However, an analysis of
      several prominent representations revealed strong differences regarding possible
      outcomes of the scheduling process and the effort needed for their assessment.
      Limitations of some representations do not only concern specific rota design
      issues, such as different staffing levels or different workhours, but also rather
      simple and straightforward rotas. Furthermore, there is no single representation
      that is strictly and unequivocally better than the others. Most representations
      simplify the development of some rotas, while they make it very difficult or even
      impossible to develop others. Therefore, both designers and the computer systems
      used for design should use and support several representations and therefore
      allow smooth transitions between them. In addition knowledge about rota
      construction techniques should be maintained, as it may ease assessment
      dramatically.

PMID- 9916825
TI  - A technique to take leave into account in shift-rota design.
AB  - Sick leave, vacations, and the like lead to substantial leave factors. Rota
      design techniques for covering leave are not always feasible. A small company was
      helped to develop a new rota. The main requirements were an ergonomically better
      rota, less overtime caused by leave, and a rota that lets employees take their
      vacation during the summer. The internal evaluation was unanimously positive
      after 1 year. A prospective leave coverage was used, with different workhours
      during summer and spring and with a mixture of shift work and flexible day work.
      Later the rota was further refined, and broader qualifications of the workers
      made a much simpler rota possible. The experiences of this study indicate that
      problems with leave can be reduced if expected variations in leave are considered
      in the rota design by including variations in workhours. A further promising
      strategy is to mix shift work with other types of work when time is not a
      critical factor.

PMID- 9916826
TI  - Diurnal trends in mood and performance do not all parallel alertness.
AB  - OBJECTIVES: This study examined the hypothesis that alertness can be used to
      predict time-of-day effects on performance. METHODS: For 6 or 7 days the
      volunteers (24, highly practiced young women) were required to retire to bed at
      0000 and were awakened at 0800. A battery of mood and performance tests was
      completed every 2 hours while the women were awake; the result was 9 equally
      spaced measures per day. Measures of mood, serial reaction time, and memory
      scanning were recorded. Rectal temperature was recorded continuously. RESULTS:
      After omitting the data from the first day to avoid any carry-over from the
      "first-night" effect on sleep, average time-of-day functions were calculated for
      each subject, for each variable, and were then z-transformed. Cross-correlations
      between the pooled time-of-day trends indicated that, while alertness was a
      reasonably good "predictor" of the simple perceptual-motor speed measures, it
      fared less well for some of the other measures. Two-way analyses of variance
      indicated that the time-of-day trend for all measures differed from that for
      alertness, although the magnitude of this difference varied substantially and,
      for some measures, was very largely due to the last reading of the day (0000).
      CONCLUSION: It is clear from these results that, while alertness may successfully
      "predict" variations in some measures of performance capability, and especially
      those of simple perceptual motor speed, care should be exercised in extrapolating
      to other performance measures.

PMID- 9916827
TI  - Effect of bright light at night on core temperature, subjective alertness and
      performance as a function of exposure time.
AB  - OBJECTIVES: This simulated night shift study measured the effects of moderate
      bright light (a 4-hour pulse starting at 2000 or 0400) during the exposure night
      and subsequent night (dim light). METHODS: Eight young males remained confined
      with little physical activity to a laboratory in groups of 4. After a night of
      reference, they were active for 24 hours; then after a morning recovery sleep,
      they were active again for 16 hours. RESULTS: Continuously measured rectal
      temperature proved to be immediately sensitive to 4 hours of bright light,
      particularly when given at the end of the night. Self-assessed alertness and also
      performance on a task with a high requirement for short-term memory were improved
      by the exposure to bright light. During the subsequent night the subjects were
      exposed only to dim light. Core temperature, subjective alertness and performance
      continued to show a time course depending on the preceding bright light exposure.
      CONCLUSIONS: Probably because evening exposure to bright light and morning sleep
      both had a phase-delaying effect, the effects on the circadian pacemaker were
      more pronounced. Thus, for practical applications in long night shifts, bright
      light can be considered to improve mood and alertness immediately but the
      possibility of modifying the circadian "clock" during subsequent nights should be
      taken into consideration, in particular after exposure to bright light in the
      evening.

PMID- 9916828
TI  - Three-process model of supervisory activity over 24 hours.
AB  - OBJECTIVES: This study used endogenous and exogenous factors to develop a model
      for sampling supervisory activity that implied consulting numerous data on
      computer systems. METHODS: The study was carried out in an automated workshop of
      a chemical plant. Five crews worked on a 3x8 hour shift system, with changes at
      0400, 1200 and 2000. Each team included 2 experienced controllers who supervised
      the process from computer systems in a control room. Starting and ending duty at
      the same time as the operators, the researchers used real time to code of all the
      screen pages selected on the computers by 8 controllers (from 4 teams) over 18
      shifts. RESULTS: The time-of-day fluctuations of the call frequency confirmed the
      existence of endogenous factors (biological rhythms or fatigue), but they cannot
      explain all the variations observed. The modeling of the data yielded the
      following 3 explanatory factors: (i) the cognitive demands of the tasks, as an
      external factor, mainly concern the impact of shift changeover characterized by a
      strong peak of information gathering at the beginning of the shift, even at 0400;
      (ii) the shift duration appears as a "fatigue" factor and reflects a rapid
      reduction of information gathering over the shift; (iii) circadian rhythms are
      characterized by a minimum of activity at night and a maximum in the afternoon.
      CONCLUSION: In other similar work situations, in addition to an essential work
      analysis, our model could help the design of shift duration or schedules for
      shift changeover.

PMID- 9916829
TI  - Shift work and sick leave.
AB  - OBJECTIVE: Shift workers working nights are known to have higher morbidity from
      certain illnesses than day workers. This study examined episodes of certified
      sick leaves of day workers and shift workers in a large industrial plant to
      examine whether slowly rotating shift work leads to increased risk of sick leave.
      METHODS: In a case-base design more than 11000 episodes of sick leave, lasting
      more than 3 days, were obtained from the sick-leave files of a chemical plant in
      Norway. The diagnoses were grouped into 5 categories according to information on
      their work schedules. The workers included in the study were divided into 3
      groups. They worked slowly rotating 3 shifts, 2 shifts without night work, and
      daytime schedules. RESULTS: For all the diagnoses the shift workers and day
      workers were evenly distributed among the cases and the referents, the odds
      ratios ranging from 0.8 to 1.2. The risk of sick leave did not change with the
      number of years in shift work. There was a higher risk of sick leave with
      musculoskeletal diagnoses among the 2-shift workers. CONCLUSIONS: In this study
      shift workers did not have a higher risk of sick leave for diseases that, in
      previous studies, have been shown to be related to shift and night work. Although
      bias may be present in the study, the results are in line with those of previous
      studies, and they suggest that even certified sick leaves are not a valid proxy
      for morbidity.

PMID- 9916830
TI  - Combined effects of shift systems and work requirements on customs officers.
AB  - OBJECTIVES: The aim of this study was to examine the combined impact of different
      shift schedules and job demands on the physical health of customs officers.
      METHODS: The following schedules were used: 4x6 hours, 3x8 hours, 2x12 hours, and
      day work. Data were collected via a questionnaire specially designed for the
      evaluation of specific job demands on the basis of ergonomic analyses in 10
      units. A correspondence analysis led to the identification of 3 variables
      representing different categories of work-related constraints, namely, physically
      demanding job, boring, monotonous job, and conflicting relations with travelers.
      These variables were included in a series of logistic regression analyses on the
      health aspects of the customs officers. RESULTS: The analyses highlighted the
      dominating effect of the 3x8 hour and 4x6 hour schedules on the occurrence of
      health problems but also showed strong effects for confrontation with travelers.
      The conflictual relations with travelers had the largest and most marked
      influence, it played a role in the area of sleep and cardiovascular and digestive
      problems. All of the 3 central job demands had an effect on sleep. CONCLUSIONS:
      The results point to a need for a multifaceted approach to research and
      intervention regarding the difficulties encountered by shift workers, from both
      the occupational medicine and the work design point of view. This conclusion
      seems particularly relevant for several professional sectors in which workers are
      confronted with both shift work and customer-focused jobs (police, prison guards,
      nurses, and the like).

PMID- 9916831
TI  - Effects of coping strategies, social support and work-nonwork conflict on shift
      worker's health.
AB  - OBJECTIVES: This study examines the direct and mediated effects of shift workers'
      coping strategies and social support on structural work-nonwork conflict and
      subjective health. METHODS: The participants were 172 registered female nurses,
      aged 21 to 40 years. They all worked full-time, on rapidly rotating, 8-hour
      shifts in metropolitan general hospitals. All the respondents completed a self
      administered questionnaire requesting demographic information and data on sources
      of social support, work-nonwork conflict, and coping strategies. RESULTS: A path
      model with good fit (chi2=28.88, df=23, P>.23, CFI=0.97) demonstrated complex
      effects of social support and coping on structural work-nonwork conflict and
      health. CONCLUSIONS: Structural work-nonwork conflict mediated the effects of
      social support from supervisors and emotionally expressive coping on
      psychological symptoms. Control of shifts mediated the effect of social support
      from supervisors on structural work-nonwork conflict. Disengagement coping had
      direct and mediated effects on psychological and physical health. However, it
      also had mediated effects, with the effect on psychological health being mediated
      by support from co-workers and the effect on physical symptoms being mediated by
      family support. Co-worker support mediated the effect of social support from
      supervisors on psychological symptoms. Overall, these findings support previous
      research and clarify the process by which coping strategies and social support
      affect structural work-nonwork conflict and health in shift work.

PMID- 9916832
TI  - The emotional impact of shift work on the children of shift workers.
AB  - OBJECTIVES: This study compared the emotional state of children of shift and day
      working fathers. METHODS: One hundred and ninety children (8 to 11 years of age)
      took part in the study. Ninety-one came from "shift working" homes, and 99 came
      from "day working" homes. Each child completed 2 questionnaires, The Harter Self
      Perception Questionnaire and the Children's Depression Inventory. RESULTS: The
      daughters of shift working fathers reported a significantly poorer perception of
      their ability in school-related activities and significantly greater
      discrepancies between their perceived overall level of competence and their ideal
      level of competence. In addition, more depressive symptomatology and a lower
      level of self-esteem were also found for the daughters of shift working fathers
      in comparison with the daughters of day working fathers. No such effects were
      found for the sons of shift working fathers. CONCLUSIONS: Parental shift working
      may be experienced as stressful within the family, and this stress may affect the
      emotional state of the child. However, the nature of expression of these
      emotional difficulties may vary according to the gender of the child. Further
      research is needed.

PMID- 9916833
TI  - Guidelines for the medical surveillance of shift workers.
AB  - Occupational health physicians should evaluate workers' fitness for shift and
      night work before their assignment, at regular intervals, and in cases of health
      problems connected with night work. The evaluation should be accompanied by a
      careful job analysis to ensure that shift schedules are arranged according to
      ergonomic criteria. This arrangement can reduce health problems and make coping
      with irregular workhours possible, even for people suffering from
      contraindicative illnesses. Both health disorders representing absolute or
      relative contraindication and actual work conditions should be taken into
      account. Health checks should be aimed at detecting early signs of intolerance,
      such as sleeping and digestive trouble, drug consumption, accidents, and
      reproductive function. Their periodicity should be set in relation to specific
      work conditions, individual characteristics, and social factors known to
      influence tolerance to shift work. Shift workers should receive clear information
      on the possible negative effect of shift work, and also counseling for coping
      with shift and night work.

PMID- 9916834
TI  - Expansile bone lesions in a three-generation family.
AB  - We report on a three-generation family with "expansile" bone lesions of the
      distal radius and ulna, cortical thickening of the proximal long bones, and
      pathologic fractures. The differential diagnosis of expansile bone lesions
      includes isolated bone cysts and tumors, such as enchondromas and fibrous
      dysplasia; familial expansile osteolysis; and the genochondromatoses. Our
      patients have findings most similar to the genochondromatoses; however, the
      distribution of the lesions and the accompanying manifestations may be evidence
      for a unique genetic condition in this family.

PMID- 9916835
TI  - Studies of the cranial base in 23 patients with cri-du-chat syndrome suggest a
      cranial developmental field involved in the condition.
AB  - The purpose of the present study was to investigate the cranial base on profile
      radiographs of patients with cri-du-chat syndrome and to relate the findings to
      current knowledge of brain malformation in an attempt to localize the
      developmental field affected in cri-du-chat syndrome. The material of profile
      radiographs of 23 patients was collected in Denmark in the 1970s. Twenty-two
      patients had terminal deletions of chromosome 5 (5p13.3, 5p14.1, 5p14.2, and
      5p14.3), and one patient had an interstitial deletion. The cranial base angle (n
      s-ba) was in most cases reduced and in no cases increased compared to age-related
      standards for normal individuals. Malformations in the bony contours of the sella
      turcica and the clivus occurred in cri-du-chat patients with terminal deletions.
      This specific cranial base region develops around the notochord at the location
      from where the rhombencephalic-derived brainstem, pons, and cerebellum have
      developed dorsally, and from where the neurons to the larynx have migrated
      ventrally. As the cranial base, the cerebellum and the larynx are involved in cri
      du-chat syndrome, and attention is drawn to a new developmental field which
      comprises the dorsum sellae, clivus, cerebellum, and larynx. This field seemingly
      originates from the same notochordal location. The study has demonstrated a
      cranial base malformation in cri-du-chat patients, which ought to be elucidated
      in future research and combined with neurological and chromosomal investigations.

PMID- 9916836
TI  - Mosaicism with a normal cell line and an unbalanced structural rearrangement.
AB  - Mosaicism with a normal cell line (N) and an unbalanced autosomal structural
      rearrangement (UASR) is rare. This report describes a case of a newborn female
      with a karyotype of 46,XX,der(4)t(4;15)(q35;q22)/46,XX. Molecular cytogenetic
      analysis confirmed the origin of the derivative chromosome 4. Here we discuss
      this case as well as other cases of mosaic karyotypes involving N/UASR.

PMID- 9916837
TI  - Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma.
AB  - We report on a 7-year-old boy with mosaic variegated aneuploidy (MVA) who
      developed embryonal rhabdomyosarcoma of the soft palate. This patient is the 11th
      case report of MVA and represents further documentation of the true existence of
      this rare mitotic mutant. Clinical findings share similarities to those
      previously described patients including microcephaly and growth retardation as
      the two most common abnormalities. Notably, mental retardation is not universally
      present. Results of serial cytogenetic analyses performed on somatic and
      neoplastic tissues are reviewed and compared with those of other previously
      reported patients. We postulate that mosaic variegated aneuploidy is causally
      related to the development of rhabdomyosarcoma in our patient. This is the first
      report of a patient with MVA who developed cancer and suggests that these
      patients may be at risk for malignancy and require long-term follow-up and cancer
      surveillance.

PMID- 9916838
TI  - FMR1 gene expression in olfactory neuroblasts from two males with fragile X
      syndrome.
AB  - The fragile X mental retardation 1 gene (FMR1) mutation is strongly correlated
      with specific and marked neurobehavioral and neuroanatomical abnormalities. The
      protein product, FMRP, is highly expressed in neurons of the normal mammalian
      brain, and absent or in low levels in leukocytes from individuals with fragile X
      (FraX)-associated mental impairment. Inferences which arise from these findings
      are that FMRP has a critical role in the development and functioning of the
      brain, and that leukocyte-derived molecular assessments provide a good indicator
      of FMR1 expression in that organ. This latter conclusion appears true in most
      cases even though the typical FMR1 mutation is an unstable triplet repeat
      expansion which demonstrates somatic heterogeneity within and across tissues.
      Blood to brain correspondence in FraX patients has only rarely been confirmed by
      the direct study of human brain specimens and, to our knowledge, it has never
      been studied in living individuals with the FMR1 mutation. In this report, we
      describe the FMR1 patterns in olfactory neuroblasts (ON) from two living brothers
      with expansion mutations in their leukocytes who are mentally retarded and
      autistic. ON were chosen for study because they are accessible neurons closely
      linked to the brain. In both subjects, the ON genotype was highly, but not
      perfectly, consistent with that observed in leukocytes. Protein phenotypes across
      tissues were completely consistent showing the absence of FMRP-immunoreactivity (
      ir). These results augment the limited amount of direct evidence which indicates
      that FMR1 mutation patterns in leukocytes are a good, albeit potentially
      fallible, reflection of such patterns in the brain. This report further
      demonstrates the feasibility of using ON samples to evaluate the FMR1 mutation in
      humans in vivo.

PMID- 9916839
TI  - Neurological involvement in a child with the wrinkly skin syndrome.
AB  - In 1973, a syndrome was reported comprising of wrinkled skin over the dorsum of
      hands, feet, and abdomen, reduced skin elasticity, skeletal involvement,
      craniofacial anomalies, mental and developmental delay, and failure to thrive.
      Only nine cases have been reported. Three additional cases with deletion 2q32
      show some manifestations of this syndrome. We present another child with this
      syndrome with prominent neurological involvement manifested by mental
      retardation, microcephaly, and an episode of status epilepticus.

PMID- 9916840
TI  - Deletion of the pseudoautosomal region in a male with a unique Y;13 translocation
      and short stature.
AB  - Short stature is a common finding in patients with Ullrich-Turner syndrome.
      Structural abnormalities involving the terminal short arms of the X and Y
      chromosomes have been shown to lead to short stature. A putative locus affecting
      height called PHOG/SHOX has been localized to a 170-kb critical region within the
      pseudoautosomal region (PAR). It contains a homeodomain and functions as a
      transcription factor. We have studied a 10-year-old boy with idiopathic short
      stature who was found to have a unique Y;13 translocation. Southern blot analysis
      using cDNA probes indicated that most of the PAR, including PHOG/SHOX, was lost
      as a result of this translocation. We conclude that haploinsufficiency for this
      gene is responsible for the growth failure in our patient. Treatment with
      recombinant growth hormone has resulted in greatly improved growth velocity.

PMID- 9916841
TI  - VACTERL manifestations in two generations of a family.
AB  - Most cases of the VACTERL "association" [Martinez-Frias et al., Am. J. Med.
      Genet. 76: 291-296, 1998] are sporadic, with an empiric recurrence risk of 1% or
      less. Rare families with recurrence of VACTERL-H association are described with
      patterns consistent with single gene inheritance. Also described are occasional
      single anomalies of the VACTERL association in sibs or parents of affected
      individuals. We describe a mother and son with typical VACTERL anomalies. The
      patient was born by cesarean section to a 27-year-old G1 mother following an
      uncomplicated pregnancy. He was found to have an asymmetric crying face, preaxial
      polydactyly on the right, a small midmuscular ventricular septal defect with an
      incomplete right bundle branch block on echocardiogram, a small cleft in T3, and
      incomplete development of the left half of the sacrum. The kidneys were normal
      ultrasonographically. The patient's mother was born with an H-type tracheo
      esophageal fistula, imperforate anus, rectovaginal fistula, a triphalangeal
      thumb, hypoplastic left kidney, and vertebral anomalies. There were no other
      individuals with VACTERL anomalies in the family. No families with VACTERL
      association in the offspring of an affected individual have been reported
      previously.

PMID- 9916842
TI  - Metaphyseal anadysplasia: evidence of genetic heterogeneity.
AB  - We report on two unrelated children, a girl and a boy, with regressive
      metaphyseal dysplasia. Both children had bow legs and a transient growth decline
      in early childhood. Metaphyseal modifications of the long bones in the children
      were most conspicuous at an early age and then subsided by age 2 to 3 years. The
      father of the boy may have had the same disorder, because he was shorter than his
      sibs and showed mild modifications of the vertebral end plates with mild
      narrowing of the interpediculate distance of the lumbar spine. The evolution of
      the metaphyseal dysplasia in the children closely resembled that of metaphyseal
      anadysplasia (MAD), which is X-linked recessive in inheritance. By contrast, the
      occurrence of an isolated, affected girl and possible father-to-son transmission
      reported here were consistent with autosomal dominant transmission, suggesting
      heterogeneity of MAD. Molecular studies of the type X collagen gene in the boy
      did not demonstrate any disease-causing mutation.

PMID- 9916843
TI  - Vascular abnormalities in Adams-Oliver syndrome: cause or effect?
AB  - We describe a young girl diagnosed with the Adams-Oliver syndrome (AOS)
      associated with double outlet right ventricle, portal hypertension, and pulmonary
      hypertension. We hypothesize that a congenital vascular abnormality is the
      underlying pathogenesis and that the cutaneous defects characteristically seen in
      AOS represent the most common manifestation of this. We suggest that AOS should
      not merely be considered a syndrome consisting of aplasia cutis congenita and
      terminal transverse limb defects but rather a constellation of clinical findings
      resulting from an early embryonic vascular abnormality.

PMID- 9916844
TI  - Perceived personal control (PPC): a new concept in measuring outcome of genetic
      counseling.
AB  - Many researchers have tried to establish criteria for the evaluation of genetic
      counseling and the assessment of its success. Most studies focused on counseling
      outcomes mainly educational and reproductive variables. In the present study we
      introduced the concept of "perceived personal control" (PPC), which captures a
      wider and more meaningful range of effects of genetic counseling. It was found to
      be central to coping with health threats and to adapting to a broad spectrum of
      health problems. This study investigated 154 counseling cases. Counselees were
      requested to complete pre- and post-counseling questionnaires consisting of a
      knowledge test, measures of PPC, expectations/evaluations of counseling, and
      satisfaction with the procedure. Comparisons of mean PPC scores before and after
      counseling showed significant increases. Higher post-counseling PPC was found
      among counselees who had been given a definite diagnosis, a specific recurrence
      risk, and been offered prenatal diagnosis. Post-counseling PPC also correlated
      with knowledge, satisfaction, counseling evaluations, and expectation
      fulfillment. The findings suggest that PPC is a valid measure for the evaluation
      of genetic counseling outcomes. The psychometrically reliable scales developed in
      this study can become helpful tools for assessing genetic counseling both in
      research and in clinical practice, helping the counselor evaluate the counseling
      session and focus on the counselees' needs.

PMID- 9916845
TI  - Diagnostic yield of the comprehensive assessment of developmental delay/mental
      retardation in an institute of child neuropsychiatry.
AB  - The Consensus Conference of the American College of Medical Genetics has
      established guidelines regarding the evaluation of patients with mental
      retardation (MR) [Curry et al., Am. J. Med. Genet. 72:468-477, 1997]. They
      emphasized the high diagnostic utility of cytogenetic studies and of neuroimaging
      in certain clinical settings. However, data on the diagnostic yield of these
      studies in well-characterized populations of individuals with MR are scant.
      Majnemer and Shevell [J. Pediatr. 127:193-199, 1995] attained a diagnostic yield
      of 63%. However, this study included only 60 patients and the classification
      included pathogenetic and causal groups. The Stella Maris Institute has evaluated
      systematically patients with developmental delay (DD)/MR and performed various
      laboratory studies and neuroimaging in almost all patients. We report a
      retrospective analysis of the diagnostic yield of 120 consecutive patients
      observed at our Institute during the first 6 months of 1996. There were 77 males
      and 43 females; 47 were mildly delayed (IQ 70-50), 31 were moderately delayed (IQ
      50-35), and 42 were severely delayed (IQ 35-20). Diagnostic studies (history,
      physical examination, standard cytogenetics, fragile X testing, molecular
      studies, electroencephalography, electromyography, nerve conduction studies,
      neuroimaging, and metabolic screening tests) yielded a causal diagnosis in 50
      (41.6%) and a pathogenetic diagnosis in 47 (39.2%) of the 120 patients. Causal
      categories included chromosomal abnormalities (14), Fra(X) syndromes (4), known
      MCA/MR syndromes (19), fetal environmental syndromes (1), neurometabolic (3)
      disorders, neurocutaneous (3) disorders, hypoxic-ischemic encephalopathy (3),
      other encephalopathies (1), and congenital bilateral perisylvian syndrome (2).
      Pathogenetic categories included idiopathic MCA/MR syndromes (35), epileptic
      syndromes (10), and isolated lissencephaly sequence (2). Diagnostic yield did not
      differ across categories and degree of DD. Our results, while confirming the
      diagnostic utility of cytogenetic/molecular genetic, and neuroimaging studies,
      suggest the usefulness of accurate electroencephalogram recordings, and stress
      the importance of a thorough physical examination. Referral to a university child
      neurology and psychiatry service, where a comprehensive assessment with a
      selected battery of investigations is possible, yields etiologic findings in a
      high percentage of DD/MR patients, with important implications for management,
      prognosis and recurrence risk estimate.

PMID- 9916846
TI  - Trizygotic pregnancy consisting of two fetuses and a complete hydatidiform mole
      with dispermic androgenesis.
AB  - A triplet pregnancy in a 23-year-old woman was terminated at 15 weeks of
      gestation because of her severe hypertension, lung edema, and secondary
      hyperthyroidism. The pregnancy consisted of a hydatidiform mole with a 46,XY
      karyotype and two fetuses each with 46,XX and a 46,XY karyotype. To determine the
      zygosity and genetic origin of the mole and fetuses, PCR- and computer-assisted
      genotyping were performed at 27 CA-repeat marker loci that were distributed
      evenly over the genome. As a result, genotypes of the three pregnancy products
      were distinct from each other, indicating that the triplets were trizygotic. The
      mole lacked any maternal alleles but inherited both of the paternal alleles
      and/or one paternal allele in duplicate. This, along with the XY sex chromosome
      constitution, indicated that the mole resulted from dispermic androgenesis. The
      mother developed a persistent trophoblastic tumor thereafter.

PMID- 9916847
TI  - Left-right axis malformations associated with mutations in ACVR2B, the gene for
      human activin receptor type IIB.
AB  - Targeted disruption of the mouse activin receptor type IIB gene (Acvr2b) results
      in abnormal left-right (LR) axis development among Acvr2b-/- homozygotes [Oh and
      Li, 1997: Genes Dev 11:1812-1826]. The resulting malformations include atrial and
      ventricular septal defects, right-sided morphology of the left atrium and left
      lung, and spleen hypoplasia. Based on these results, we hypothesized that
      mutations in the type IIB activin receptor gene are associated with some cases of
      LR axis malformations in humans. We report here characterization of the ACVR2B
      genomic structure, analysis of ACVR2B splice variants, and screening for ACVR2B
      mutations among 112 sporadic and 14 familial cases of LR axis malformations. Two
      missense substitutions have been identified, one of which appears in two
      unrelated individuals. Neither of these nucleotide changes has been found in 200
      control chromosomes. We conclude that ACVR2B mutations are present only rarely
      among human LR axis malformation cases.

PMID- 9916848
TI  - Genetic mapping of a novel familial form of infantile hemangioma.
AB  - Infantile hemangiomas are the most common tumor of infancy, occurring with an
      incidence of up to 10% of all births. They are benign but highly proliferative
      lesions involving aberrant localized growth of capillary endothelium. Although
      most hemangiomas occur sporadically and as single lesions, or in conjunction with
      pleiotropic genetic syndromes, we have previously identified six kindreds where
      hemangiomas appear to segregate as an autosomal dominant trait with high
      penetrance. Four such families contain affected individuals in three or more
      generations. In the current study, blood samples from five of these families were
      collected and used in a whole genome linkage search at 10-cM resolution. We
      established evidence for linkage to 5q in three families, and evidence for locus
      heterogeneity. The three 5q-linked families were further genotyped to generate
      haplotype information and narrow the candidate interval. Based on recombination
      breakpoint analysis, the interval exists between markers D5S2490 and D5S408,
      spanning 55 cM, and corresponding to 5q31-33. Using information from affected and
      unaffected individuals, the interval spans 38 cM between markers D5S1469 and
      D5S211. Three candidate genes involved with blood vessel growth map to this
      region: fibroblast growth factor receptor-4 (FGFR4), platelet-derived growth
      factor receptor-beta (PDG-FRB), and fms-related tyrosine kinase-4 (FLT4). The
      genes and gene products associated with familial hemangiomas may be involved
      somatically in the more common sporadic cases.

PMID- 9916849
TI  - Autosomal recessive syndrome of growth and mental retardation, seizures, retinal
      abnormalities, and osteodysplasia with similarity to the Gurrieri syndrome.
AB  - We report on two sibs, brother and sister, with a multiple congenital
      anomaly/mental retardation syndrome consisting of severe growth and mental
      retardation, seizures, retinal abnormalities, osteodysplasia, brachydactyly,
      prognathism, and dental malocclusion. These clinical findings were present in
      both patients and seem to be consistent with the phenotype of the Gurrieri
      syndrome. The new features described in these sibs could expand the clinical
      spectrum of the Gurrieri syndrome and confirm the existence of this rare
      autosomal recessive condition.

PMID- 9916850
TI  - Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes.

PMID- 9916851
TI  - Inverted duplication/deletion of chromosome 8p: mild clinical phenotype.

PMID- 9916852
TI  - Can we rely on family history?

PMID- 9916853
TI  - Heterogeneity in omphalocoele with absent radial ray complex.

PMID- 9916854
TI  - Lethal multiple pterygium syndrome in four male fetuses in a family: evidence for
      an X-linked recessive subtype?

PMID- 9916855
TI  - Case of apparent Gurrieri syndrome showing molecular findings of Angelman
      syndrome.

PMID- 9916856
TI  - Thyroid defects due to Pax8 gene mutations.

PMID- 9916857
TI  - The role of high- and low-dose corticotropin tests in the diagnosis of secondary
      adrenal insufficiency.

PMID- 9916858
TI  - Transcriptional regulation by cyclic AMP is essential for development,
      reproduction and survival: lessons from the transgenic mice.

PMID- 9916859
TI  - The one microgram adrenocorticotropin test in the assessment of hypothalamic
      pituitary-adrenal function.
AB  - The possibility of assessing hypothalamic-pituitary-adrenal (HPA) function by the
      standard ACTH test (250 microg) has been widely discussed in the past years and
      compared with the role of the insulin tolerance test (ITT). Recently, it was
      shown that low doses of ACTH, such as 1 microg i.v., induce a maximal adrenal
      response and, by reducing the discrepancies compared with the ITT also allow one
      to detect mild forms of secondary hypoadrenalism. In the present study the 1
      microg ACTH test was performed in patients with hypothalamic-pituitary disease in
      order to assess adrenal function, and the results have been compared with those
      obtained after the insulin test. Fifty-seven patients (31 men and 26 women, aged
      19-73 years) with hypothalamic-pituitary diseases were studied: 51 patients were
      affected with pituitary tumor and 6 patients had hypothalamic disorders. All
      these patients and 18 healthy volunteers (7 men and 11 women, aged 19-46 years)
      received 1 microg i.v. ACTH injection. In addition, the ITT (0.1-0.15 U/kg body
      weight) was performed in all patients. In normal subjects mean cortisol levels
      significantly (P<0.001) increased from a baseline of 393+/-43 nmol/l to a peak of
      770+/-41 nmol/l after 1 microg ACTH. In 44 patients with hypothalamic-pituitary
      disease 1 microg ACTH caused a cortisol rise similar to that of normal subjects
      (from 332+/-17 to 769+/-24 nmol/l; P<0.001), while an impaired response (from
      124+/-23 to 312+/-46 nmol/l) was observed in 13 cases (23%), 7 of them with low
      morning cortisol levels (10-127 nmol/l) and 6 with basal values at the lower
      limit of normality. The cortisol response to ITT was compared with that obtained
      after the 1 microg ACTH test: 10 patients failed both challenges, 4 patients who
      passed the ACTH test failed the ITT, while 3 patients who failed the ACTH test
      passed the ITT. The 23 out of 57 patients (40%) who showed a cortisol peak
      greater than 750 nmol/l after 1 microg ACTH had a normal response to ITT. A
      positive correlation between cortisol peaks after ACTH and after insulin was also
      found (r = 0.68, P<0.001). Assuming a 100% accuracy of ITT, the low dose ACTH
      test yielded a 71% sensitivity and a 93% specificity. In conclusion, the low-dose
      ACTH test is a useful, safe and inexpensive tool for the initial assessment of
      HPA function in patients with hypothalamic-pituitary disease. In fact, the ITT is
      unnecessary when cortisol peaks are greater than 750 nmol/l after 1 microg ACTH
      and also when very low cortisol basal levels indicate an overt hypoadrenalism.
      Within these limits the ITT is mandatory and its important role in the
      recognition of secondary adrenal failure is further confirmed.

PMID- 9916860
TI  - How reliable is the short synacthen test for the investigation of the
      hypothalamic-pituitary-adrenal axis?
AB  - The best test for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis
      remains a matter of controversy. We compared the performance of the short
      synacthen test (SST, 250 microg) with the insulin stress test (IST) to assess the
      reliability of the former as a first line test. Patients with pituitary disease
      underwent both the SST and the IST. The results in patients who had both tests
      within 4 weeks of each other, and where these were not separated by a therapeutic
      intervention, were compared. Basal, 30 and 60 min cortisol levels were obtained
      from the SST. Basal and maximal cortisol level after adequate hypoglycaemia
      (glucose<2.2 mmol/l) were recorded for the IST. Sixty-nine paired test results
      were available for analysis. With a 30 min 'pass' plasma cortisol value of 500
      nmol/l on the SST, 7/69 (10%) patients who passed the SST failed the IST set at a
      'pass' maximum value of 500 nmol/l. At a 'pass' cortisol value of 600 nmol/l on
      the SST, 3/69 (4%) who passed the SST failed the IST. Assuming the IST as the
      gold standard, the sensitivity of an SST 'pass' of 600 nmol/l is 85% with a
      specificity of 96%. During the conventional dose SST (250 microg) a 30 min plasma
      cortisol value of 600 nmol/l is more reliable than a value of 500 nmol/l, and
      using the former criterion the SST can safely be used as a first line test for
      the evaluation of the HPA axis in patients with pituitary disease. However, if
      the result is borderline or there is clinical suspicion of mild
      hypocorticotrophism an IST or other test of the HPA axis may be warranted.

PMID- 9916861
TI  - Guidelines for TSH-receptor antibody measurements in pregnancy: results of an
      evidence-based symposium organized by the European Thyroid Association.

PMID- 9916862
TI  - Relationship between serum TSH and the responsiveness of toxic solitary
      autonomous thyroid nodules to radioiodine therapy.
AB  - OBJECTIVE: To investigate if serum TSH at the time of 131I therapy influences the
      outcome. DESIGN: A retrospective analysis of data on 39 consecutive patients with
      toxic solitary autonomous thyroid nodules treated with 131I during a 4 year
      period. METHODS: Serum TSH was determined by an ultrasensitive RIA with a
      functional sensitivity of 0.03 mU/l. The 131I dose was calculated blind to the
      actual serum TSH according to a model compensating for thyroid size estimated by
      palpation as well as 24 h 131I uptake. RESULTS: After a mean follow-up period of
      30 months, 34 patients (87% of all patients) were euthyroid, three (8%) had
      responded insufficiently and required further antithyroid therapy, and two (5%)
      had developed hypothyroidism. No significant difference in the response pattern
      between patients with suppressed or detectable serum TSH could be demonstrated.
      The two patients who developed hypothyroidism both had detectable serum TSH at
      the time of 131I treatment. No other clinical parameter seemed to influence the
      outcome. CONCLUSION: There is no clinically significant effect of circulating TSH
      on the response of toxic solitary autonomous thyroid nodules to 131I therapy.
      However, keeping the patients subclinically hyperthyroid when receiving 131I
      treatment may possibly result in a reduced frequency of hypothyroidism.

PMID- 9916863
TI  - Circulating leptin level and growth hormone response to stimulation tests in
      obese and normal children.
AB  - OBJECTIVE: Growth hormone secretion is decreased in obese subjects, and their GH
      response to stimulation tests is blunted. The mechanisms relating excess adipose
      mass and GH secretion are unknown. We hypothesized that leptin might be a signal
      linking adipose mass to GH secretion. DESIGN: We measured serum leptin levels and
      the GH response to stimulation tests in 42 obese and 40 lean short normal
      prepubertal children. RESULTS: The mean serum leptin concentrations were 23.8+/
      1.7 ng/ml and 3.6+/-0.4 ng/ml in obese and lean children respectively, and were
      found to be inversely related to GH peak in both groups. After adjusting for body
      fat data, leptin was still an independent predictor of GH peak. Multiple stepwise
      regression analysis identified both leptin (regression coefficient = -0.78, P =
      0.001), and insulin (regression coefficient = -0.03. P = 0.009) as negative
      determinants of GH response to the GHRH test in obese children (multiple R =
      0.64), and only leptin in lean children (r = -0.51, P = 0.001). No correlation
      was observed between leptin and IGF-I or IGF binding protein-3. CONCLUSION: These
      results are consistent with the hypothesis that leptin could contribute to the
      regulation of GH secretion.

PMID- 9916864
TI  - Insulin resistant phenotype is associated with high serum leptin levels in
      offspring of patients with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To investigate whether there are differences in serum leptin levels
      between the offspring of non-insulin-dependent diabetes mellitus (NIDDM) patients
      representing different phenotypes of NIDDM, and furthermore to investigate the
      role of different fat tissue (subcutaneous fat area (SCFAT) and intra-abdominal
      fat area (IAFAT)) and insulin sensitivity on serum leptin levels. DESIGN: Twenty
      non-diabetic offspring of NIDDM patients with insulin secretion deficient
      phenotype (IS-group), 18 non-diabetic offspring of NIDDM patients with insulin
      resistant phenotype (IR-group) and 14 healthy control subjects without a family
      history of diabetes were studied. METHODS: Serum leptin levels were measured by
      RIA. SCFAT and IAFAT were measured by computed tomography. the total fat mass
      (TFM) by bioelectrical impedance and the whole body glucose uptake (WBGU) by the
      euglycemic hyperinsulinemic clamp technique. RESULTS: Subjects of the control
      group (P = 0.003) and the IS-group (P<0.001) had lower serum leptin levels than
      subjects of the IR-group even after adjustment for gender (P<0.001). TFM (P =
      0.009), fasting plasma insulin (P = 0.003) and for IAFAT (P<0.001). The
      differences weakened after adjustments for SCFAT (P = 0.028) or WBGU (P = 0.040)
      and disappeared after adjustment for both SCFAT and WBGU (P = 0.058). In the
      stepwise multiple regression analyses SCFAT. WBGU and gender explained 58% of the
      variation of serum leptin levels whereas IAFAT failed to be a significant
      determinant of serum leptin levels. CONCLUSIONS: The higher serum leptin levels
      in the IR-group was markedly, but not solely, explained by lower rates of WBGU
      and higher SCFAT. SCFAT was shown to be a more important determinant of serum
      leptin levels than IAFAT among these study groups.

PMID- 9916865
TI  - GH stimulation tests: evaluation of GH responses to heat test versus insulin
      tolerance test.
AB  - OBJECTIVE: Heat exposure has been shown to stimulate GH release, but the
      specificity and the reproducibility have not been determined, and the test has
      not been compared with validated GH stimulation tests in adulthood. We therefore
      tested the specificity and the reproducibility of the heat exposure test in
      healthy subjects and compared the results with those obtained with the insulin
      tolerance test (ITT). DESIGN: Ten healthy non-obese men, aged 31.3+/-4.80 years,
      underwent four GH stimulation tests in random order: two ITTs and two heat
      exposure tests. In the heat test, subjects were placed in a hot bath with water
      temperature at 40.3+/-0.11 degrees C for 45 min, resulting in an identical (P =
      0.477) significant increase in tympanic temperature of 1.26+/-0.05 and 1.41+/
      0.07 degrees C in the two tests. RESULTS: Peak GH response to the heat exposure
      test was less than the peak GH response to ITT (5.25+/-1.72 vs 15.5+/-3.17
      microg/l, P = 0.006). Furthermore the specificity (arbitrary cut-off level = 3
      microg/l) of the heat test was lower than of the ITT (8/17 vs 18/20, P = 0.006).
      The coefficient of variation did not differ between the two tests (heat test
      0.31, ITT 0.36, P = 0.77). Peak GH values in the individual tests were highly
      correlated (heat, r = 0.908, P = 0.002; ITT, r = 0.815, P = 0.004). Reproducible
      increments in the circulating levels of stress hormones were observed during ITT.
      but these hormones remained largely unchanged during heat exposure. CONCLUSIONS:
      The heat exposure test is not a reliable GH stimulation test compared with the
      ITT in adults. This study documents that the ITT has a high specificity and
      reproducibility in the diagnosis of GH deficiency in adulthood. We propose that
      the heat exposure test is not used in the diagnosis of this condition in
      adulthood.

PMID- 9916866
TI  - Dissociation of adrenomedullin concentrations in plasma and cerebrospinal fluid
      in pregnant and non-pregnant women.
AB  - Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within
      the central nervous system to modulate fluid and electrolyte balance. AM
      immunoreactive cells have been found in the anterior pituitary gland and the
      choroid plexus of humans. In addition, AM activity has been implicated in the
      regulation of maternal circulation during pregnancy. To determine the
      relationship between AM concentration in the cerebrospinal fluid (CSF) and
      plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and
      non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or
      obstetric surgery. In both groups, the concentration of AM in the plasma exceeded
      that in the CSF. Plasma AM concentration was significantly higher in pregnant
      than non-pregnant women (17.3+/-5.8 vs 5.1+/-1.4 pmol/l, mean +/- S.D.; P<0.01),
      whereas CSF AM concentration did not differ between the two groups (1.3+/-0.9 and
      0.9+/-0.4 pmol/l in groups P and NP respectively). No significant correlation was
      found between AM concentrations in the CSF and plasma. The present findings
      suggest that AM is present in the CSF and that its concentration in the CSF is
      regulated independently from that in the plasma.

PMID- 9916867
TI  - Variations in glucocorticoid levels within the physiological range affect plasma
      leptin levels.
AB  - OBJECTIVE: Leptin, the obese gene product, is thought to regulate body fat
      through its action on hypothalamic receptors that influence satiety. The hormonal
      regulation of leptin is important, since it might affect adiposity. Leptin
      regulation in man is poorly understood. We studied the relation between
      endogenous cortisol and leptin levels as well as the acute and chronic effects of
      a low dose of dexamethasone (DEX) on plasma leptin levels in healthy male
      volunteers. SUBJECTS AND EXPERIMENTAL PROTOCOL: The correlation between basal
      plasma levels of leptin and cortisol and the chronic effect of DEX treatment were
      studied in 12 subjects. Plasma leptin and cortisol levels were determined every
      other hour for 24 h, before and after 2 weeks of oral administration of 0.1 mg
      DEX twice daily. The acute effect was studied in 20 subjects, who received 1 mg
      DEX at 2300 h. Fasting blood samples were taken at 0800 h on the same day (i.e.
      before DEX) and on the day after. RESULTS: Under basal conditions, we found a
      correlation between mean plasma levels of leptin and cortisol (r = 0.7, P<0.02).
      Mean plasma leptin levels had increased by 50% after 2 weeks of DEX treatment
      (P<0.05). The circadian rhythm of leptin was preserved, but the night peak
      occurred 2.5 h earlier (P<0.05). Fasting plasma leptin levels were 20% higher 9 h
      after 1 mg DEX orally than at the same time on the day before (P<0.002).
      CONCLUSION: Physiological variations in cortisol are involved in the regulation
      of leptin.

PMID- 9916868
TI  - Augmented frequency and mass of LH discharged per burst are accompanied by marked
      disorderliness of LH secretion in adolescents with polycystic ovary syndrome.
AB  - The aim of this study was to quantify pulsatile LH secretion, burst frequency and
      mass, LH half-life, and the approximate entropy (ApEn) or (dis-) orderliness of
      LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high
      precision immunofluorimetric LH assay with deconvolution techniques. We sampled
      LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean +/-
      S.E.M. age 16.4+/-0.57 years, body mass index (BMI) 24.4+/-1.6 kg/m2) and 11
      eumenorrheic early-follicular-phase controls (mean +/- S.E.M. age 16.5+/-0.47
      years, BMI 22.2+/-1.0 kg/m2). Fasting serum levels of androstenedione,
      testosterone, 17-hydroxyprogesterone (17-OHP), estrone, estradiol, FSH and sex
      hormone-binding globulin (SHBG) were determined. Compared with euandrogenic
      girls, PCOS adolescents had significantly (P<0.005) elevated serum LH/FSH ratios,
      17-OHP, androstenedione, esterone and testosterone levels, decreased SHBG, and
      similar estradiol. PCOS subjects exhibited a 3-fold higher mean serum LH
      concentration with almost no overlap with controls (8.8+/-1.2 and 2.8+/-0.3 IU/l
      respectively, P<0.001). We initially used a conventional serum hormone
      concentration peak analysis method (Cluster) to evaluate the characteristics of
      pulsatile LH release. Cluster analysis disclosed a significant increase in serum
      LH concentration maximal peak height, a higher LH peak frequency and a higher
      mean serum LH concentration in interpulse nadirs in the PCOS group. Deconvolution
      analysis of mechanisms underlying the foregoing showed higher frequency in the
      PCOS group than the controls (7.9+/-0.4 and 5.7+/-0.6 pulses/12 h respectively,
      P<0.05). The mass of LH released per secretory event was also significantly
      higher in PCOS subjects than controls (5.4+/-0.57 and 3.4+/-0.56 IU/l
      respectively, P<0.05). Since the pulsatile production rate is the product of the
      mean mass of hormone secreted per pulse and the number of pulses per day, we
      estimated a significantly higher mean pulsatile production rate of (endogenous)
      LH in the PCOS group (41+/-4.2 IU/l per day in the PCOS group vs 18+/-2.3 IU/l
      per day in the controls, P<0.01). The mean estimated half-life of endogenous LH
      disappearance was also significantly higher in patients with PCOS than in
      controls (110+/-8.5 and 77+/-3.7 min respectively, P<0.01). To quantify the
      orderliness of LH release, we used ApEn. PCOS patients had remarkably increased
      disorderliness (higher ApEn) of LH release (1.09+/-0.04 vs 0.77+/-0.08 in
      controls, P = 0.002). Mean serum LH concentration, mass of LH secreted per burst,
      and LH production rate in PCOS, but not in normal adolescents, correlated
      positively with androstenedione (P<0.02, 0.02 and 0.05 respectively). The same
      parameters also correlated positively with 17-OHP (P<0.05, 0.02 and 0.05
      respectively). Stepwise regression analysis unmasked a negative influence of BMI
      in PCOS on both mass of LH secreted per burst (r = -0.77, P<0.005) and LH
      production rate (r = -0.70, P<+/0.01). We conclude that PCOS adolescents secrete
      LH molecules with amplified frequency and burst mass and with markedly disrupted
      orderliness. A rise in basal (non-pulsatile) LH release, more basic LH isoforms,
      and/or a prolongation or asymmetry of the LH secretory burst could account for
      the apparently prolonged LH half-life. Determining whether disorderliness of the
      amplified pituitary LH release process is an intrinsic abnormality in PCOS. or
      reflects androgen excess, may help to clarify the pathophysiology of this oligo
      ovulatory syndrome in young women.

PMID- 9916869
TI  - Autosomal dominant familial hypoparathyroidism and sensorineural deafness without
      renal dysplasia.
AB  - OBJECTIVE: A family is described which has a unique combination of autosomal
      dominant hypoparathyroidism and sensorineural deafness without renal dysplasia.
      CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures
      for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040
      g. His initial calcium, phosphorus and percentage of tubular reabsorption of
      phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range
      5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values
      for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities
      were found by renal imaging and a routine renal function study. He showed a brisk
      plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal
      karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ
      hybridization method. Five family members were affected with hypoparathyroidism
      with sensorineural deafness with autosomal dominant transmission. The study of
      calcium-sensing receptor and preproPTH gene showed a normal DNA sequence.
      CONCLUSION: The combination of familial hypoparathyroidism with sensorineural
      deafness without renal dysplasia is novel and the cause may be distinct from
      previously reported familial hypoparathyroidism with sensorineural deafness and
      renal dysplasia.

PMID- 9916870
TI  - Evolution of childhood central diabetes insipidus into panhypopituitarism with a
      large hypothalamic mass: is 'lymphocytic infundibuloneurohypophysitis' in
      children a different entity?
AB  - We report on a 15-year-old girl who had presented with acute onset central
      diabetes insipidus at the age of 8 years; this was followed by growth failure due
      to acquired growth hormone deficiency. Initial magnetic resonance imaging showed
      a uniformly enlarged pituitary stalk and absence of posterior pituitary
      hyperintensity. Frequent patient examination and magnetic resonance imaging gave
      unchanged results until after 5 years a large hypothalamic mass and
      panhypopituitarism were found. Dynamic magnetic resonance imaging documented
      hypothalamic-pituitary vasculopathy. Histopathological examination revealed
      perivascular inflammatory lymphoplasmic infiltrates with no granulomatosis or
      necrosis and negative staining for S-100 protein, suggesting autoimmune
      inflammatory disease (lymphocytic infundibuloneurohypophysitis?). The response to
      glucocorticoid pulses (30 mg/kg per day for 3 days i.v.) was favorable. the
      hypothalamic mass being halved and partial anterior pituitary function recovery
      maintained for 2 years after the start of treatment. We suggest that long-term
      surveillance is needed for isolated and chronic thickening of the pituitary stalk
      and that dynamic magnetic resonance imaging can contribute to the demonstration
      of hypothalamic-pituitary vascular impairment associated with local vasculitis.

PMID- 9916871
TI  - Antiphospholipid syndrome, adrenal failure, dilated cardiomyopathy and chronic
      hepatitis: an unusual manifestation of multiorgan autoimmune injury?
AB  - The antiphospholipid syndrome is characterized by clinical evidence of arterial
      or venous thrombosis, thrombocytopaenia, recurrent fetal loss and repeated
      positivity of antiphospholipid autoantibodies. The association of
      antiphospholipid syndrome with the development of adrenal failure has been
      reported in more than 40 patients in the last 20 years, mostly due to bilateral
      cortical haemorrhage or thrombosis of adrenal vessels. The presence of antibodies
      against adrenal cortex was never documented in these patients. Here we report a
      case of recurrent thrombophlebitis, acute adrenal failure, and chronic hepatitis
      occurring in a young man found to have antiphospholipid antibodies and lupus
      anticoagulant. Autoantibodies against adrenal cortex were detected and abdominal
      ultrasonography showed morphologically normal adrenals. Mild thrombocytopaenia,
      Coomb's positive anaemia, increase in alanine- and aspartate-aminotransferases
      and increase in urinary protein excretion were found. Autoantibodies against
      liver/kidney microsomes were positive and liver biopsy was compatible with
      autoimmune hepatitis. The patient was treated with cortisone acetate,
      fludrocortisone and warfarin. Dilated cardiomyopathy was revealed one year later
      and coronarography did not document any occlusive coronary disease. Three years
      later, titres of autoantibodies, including those directed towards the adrenal
      cortex, were increased and others, previously absent, were detected.
      Nevertheless, the patient's clinical conditions seemed unchanged. At this time,
      an abdominal CT scan showed adrenal dysmorphisms with bilateral annular
      calcifications and central hypodensities suggesting previous bilateral adrenal
      haematomas. The hypercoagulable state that occurs in antiphospholipid syndrome
      can induce a localized inflammatory response generated by tissue injury, with a
      consequent release of intracellular antigens and antibodies production.
      Consequently, tissue-specific autoantibodies positivity may persist until the
      cells involved in antigen production are completely destroyed.

PMID- 9916872
TI  - Novel translational repressor (NAT-1) expression is modified by thyroid state and
      age in brain and liver.
AB  - The technique of reverse transcriptase-polymerase chain reaction differential
      display was used to identify thyroid hormone (TH) responsive mRNAs in the adult
      rat cerebral tissue. A partial cDNA (0.76 kb) was cloned and sequenced.
      Comparison of the sequence to the GenBank data base showed almost 100% homology
      to mouse translational repressor (NAT-1) mRNA 3'-end. In a northern blot analysis
      this cDNA hybridized with a mRNA whose expression in hyperthyroid rat cerebral
      tissue was approximately 6-fold higher than in euthyroid rats. The time course
      studies showed a rapid induction of this mRNA within 3 h following thyroxine
      administration. This mRNA is widely expressed in various tissues, and in hepatic
      tissue it is also TH responsive. To determine if TH responsiveness of this mRNA
      persists during aging, 25-month-old aged rats were studied and the results were
      compared with those of 4-month-old rats. Unlike young mature rats, the TH
      responsiveness of NAT-1 mRNA in both the cerebral and hepatic tissue of aged rats
      was blunted. It is concluded that cerebral tissue in aging rats beyond the
      developmental stages, like the hepatic tissue, is associated with altered TH
      responsiveness.

PMID- 9916873
TI  - Genetic analysis of non-insulin-dependent diabetes mellitus in KK and KK-Ay mice.
AB  - The KK mouse is considered suitable as a polygenic model for human non-insulin
      dependent diabetes mellitus. To identify the quantitative trait loci (QTLs)
      responsible for hyperglycemia and impaired glucose tolerance in KK mice, linkage
      analysis using 97 microsatellite markers was carried out in a 192 F2 progeny,
      comprising 93 mice with the a/a genotype at the agouti locus (chromosome 2) and
      99 mice with the Ay/a genotype, produced by a cross between a C57BL/6J female and
      a KK-Ay (Ay congenic) male. In F2 a/a progenies, we identified a QTL for fasting
      glucose levels on chromosome 6 (LOD score 6.0) and three loci with suggestive
      linkage on chromosomes 3, 5 and 14, but could not identify loci accounting for
      glucose tolerance and plasma insulin levels. In F2 Ay/a progenies, there were no
      loci with statistically significant linkage, but three suggestive loci were
      identified: a locus for fasting glucose on chromosome 9, and two loci for glucose
      tolerance on chromosomes 1 and 8. It would thus appear that. although the fasting
      glucose level is controlled by QTLs in KK mice, these QTLs may be masked by the
      strong hyperglycemic influence of the Ay allele. Suggestive loci accounting for
      glucose tolerance may interact with the Ay allele, since these loci were
      identified only in F2 Ay/a progeny. This is consistent with the finding that the
      impaired glucose tolerance in KK mice is moderate and becomes overt when
      associated with the Ay allele.

PMID- 9916874
TI  - Abstracts of the International Myasthenia Gravis Workshop. November 8-10 (1998),
      Mysore, India.

PMID- 9916875
TI  - L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration
      of noradrenergic nerve fibers in the spleens of old F344 rats.
AB  - Previously, we have hypothesized a causal relationship between some measures of
      immunosenescence and the age-related decline in sympathetic noradrenergic (NA)
      nerve fibers in spleen and lymph nodes of F344 rats. In the present study, we
      investigated this interrelationship further by measuring NK cell activity, Con A
      induced IL-2 production, norepinephrine (NE) concentration, and morphological
      localization of NA and neuropeptide-Y (NPY) nerve fibers in the spleens of old
      (21 months old) male F344 rats after 10 weeks of daily treatment with low doses
      of L-deprenyl, an irreversible monoamine oxidase-B inhibitor, followed by a 9-day
      wash-out period. NK cell activity and Con A-induced IL-2 production were
      increased in deprenyl-treated old rats in comparison to untreated and saline
      treated old rats. Deprenyl treatment did not alter the percentage of CD5+ T
      cells, but moderately increased the percentage of sIgM+ B-cells in the spleens of
      old rats. In addition to changes in immune responses, NE content and the volume
      density of NA and NPY nerve fibers were partially augmented in the spleens of
      deprenyl-treated old rats. In a separate study, various concentrations of
      deprenyl were added in vitro to spleen cells from young and old F344 rats to
      examine the direct effects of the drug on Con A-induced IL-2 production. In
      contrast to in vivo treatment, in vitro addition of deprenyl did not alter the
      Con A-induced IL-2 production by splenocytes from old rats. Together, these
      results suggest that the ability of deprenyl to enhance certain immune responses
      are interlinked to the restoration of sympathetic NA and NPY nerve fibers in the
      spleens of old rats.

PMID- 9916876
TI  - Magnetic resonance imaging of PLP-induced experimental allergic encephalomyelitis
      in Lewis rats.
AB  - An in vivo magnetic resonance (MR) imaging study was performed on experimental
      allergic encephalomyelitis (EAE) induced in Lewis rats through proteolipid
      protein (PLP). PLP was solubilized in water or in an aqueous solution of 1% 10
      tridecyl ether (TDE), a non-ionic detergent used in membrane protein research.
      All 16 rats immunized with 500 microg of TDE-solubilized PLP developed clinical
      signs and MR abnormalities fully comparable to those observed in MBP-induced EAE.
      Total paraplegia was observed in 12.5% of rats, mild or moderate paraparesis in
      68.8% of rats and tail paralysis in the remaining 18.7% of rats. Whereas only
      37.5% of the eight rats immunized with 500 microg of water-solubilized PLP
      developed minor clinical signs (tail weakness or paralysis). Our observations
      confirm that the difficulties encountered when trying to induce EAE by means of
      PLP arise from the highly hydrophobic nature of this protein. Accordingly, if a
      reproducible model is to be developed, it seems more judicious to use non-ionic
      detergents in both the extraction and solubilization phases of PLP preparation,
      this would allow maximal solubilization of the protein while avoiding aggregates,
      which may otherwise form during either of the PLP preparation.

PMID- 9916877
TI  - Advanced laboratory techniques for diagnosing Toxoplasma gondii encephalitis in
      AIDS patients: significance of intrathecal production and comparison with PCR and
      ECL-western blotting.
AB  - The polymerase chain reaction (PCR) for detection of cerebral spinal fluid (CSF)
      Toxoplasma gondii DNA was combined with the study of intrathecal antibody
      synthesis by antibody specific index calculation (ASI) and the detection of
      specific oligoclonal IgG bands (OCB) by affinity mediated immunoblotting (AMI) in
      11 AIDS patients with T. gondii encephalitis (TE) and in 20 control patients with
      or without neurological disorders. Enhanced chemiluminescence (ECL) western-blot
      technique was employed to evaluate the antigenic specificity of CSF-IgG towards
      individual T. gondii antigens. PCR was positive in all TE patients which
      displayed brain-derived or blood-derived specific OCB, even when comparative ASI
      failed. Four TE patients had a unique anti-T. gondii OCB restricted to the CSF
      and a strong antibody response toward the 29 kDa band by ECL western blot. This
      response could be an important marker to discriminate TE from other opportunistic
      central nervous system (CNS) infections in the course of AIDS.

PMID- 9916878
TI  - Microglial/macrophage accumulation during cuprizone-induced demyelination in
      C57BL/6 mice.
AB  - To study microglial/macrophage infiltration, a cuprizone-induced model for
      demyelination in C57BL/6 mice was established. Cuprizone is known to cause
      demyelination in Swiss mice, however, cuprizone-induced demyelination in C57BL/6
      mice has not been previously described. Induction of demyelination in C57BL/6
      mice enables examination of the function of microglia/macrophage through
      comparative analyses of syngeneic mice with various targeted genetic mutations.
      In this report, cuprizone-induced demyelination is easily inducible, localized,
      and predictable. Concurrent with the initiation of demyelination, we noted
      microglial/macrophage accumulation and changes in astrocyte morphology.
      Astrogliosis promptly followed microglia/macrophage recruitment. These
      observations suggested that microglia/macrophage actively contribute to the
      demyelination process.

PMID- 9916879
TI  - IL-10 gene transfer to intracranial 9L glioma: tumor inhibition and cooperation
      with IL-2.
AB  - This study examines the effects of interleukin-10 (IL-10) and combination IL-10 +
      IL-2 gene transfer on experimental brain tumor growth in vivo. 9L gliosarcoma
      cells were engineered to stably express murine IL-10 (9L-IL-10 cells) and
      implanted subcutaneously or to the caudate/putamen of syngeneic rats. The growth
      of tumors expressing IL-10 was substantially reduced compared to that of control
      tumors (p < 0.05). Intracranial tumors expressing IL-10 and IL-2 were established
      by co-implanting 9L-IL-10 cells with endothelial cells engineered to express IL
      2. At 14 days post-implantation, tumors expressing IL-10 + IL-2 were 99% smaller
      than control-transfected tumors (p < 0.0001). This extent of anti-tumor effect
      could not be achieved by expression of IL-10 or IL-2 alone within tumors. Neither
      IL-10 nor a combination of IL-10 + IL-2 gene delivery inhibited tumor growth in
      severe combined immunodeficient (SCID-Beige) mice (p > 0.05). Immunohistochemical
      analysis revealed that IL-10 + IL-2 gene delivery markedly increased T-cell
      infiltration within the striatum ipsilateral to tumor cell implantation. These
      findings establish that IL-10 expression, particularly in combination with IL-2
      expression, can have significant immune-dependent anti-tumor actions within
      intracranial gliomas.

PMID- 9916880
TI  - Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol:
      functional and biochemical parameters.
AB  - We studied the effect of acute (1 h) or chronic exposure (7 and 14 days) to
      delta9-tetrahydrocannabinol (delta9-THC) on immune parameters in male Swiss mice.
      One hour after a dose of 10 mg/kg s.c., the splenocyte proliferative response to
      ConA and NK activity were not inhibited, but there was a significant decrease in
      the production of IL-2. After 7 days of treatment, when mice were tolerant to
      delta9-THC-induced analgesia, these functional parameters were strongly inhibited
      and there was a persistent reduction in IL-2 and IFNgamma. With 14 days exposure
      to the drug, splenocyte proliferation was significantly reduced only with 5
      microg/ml ConA, and NK activity was still significantly depressed (about 37%). IL
      2 had returned to the control value, whereas IFNgamma was still 40% down. Flow
      cytometry analysis of spleen cell composition indicated no changes after the
      acute and 7 day treatments, but at 14 days there was a 20% decrease in the number
      of T lymphocytes, mirrored by a 26% increase of B lymphocytes. In conclusion, in
      vivo exposure to psychoactive doses of delta9-THC has profound effects on immune
      function. This implies some important questions in relation to the liberalization
      of marijuana and its therapeutic uses.

PMID- 9916881
TI  - Reactive oxygen species are required for the phagocytosis of myelin by
      macrophages.
AB  - Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of
      multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). In
      this study we showed that the phagocytosis of myelin by macrophages triggers the
      production of ROS. We also demonstrated that ROS play a crucial role in the
      myelin phagocytosis. Blocking the ROS production with NADPH oxidase inhibitors
      (100 microM DPI or 10 mM Apocynin) essentially prevented the phagocytosis of
      myelin. Furthermore, scavenging of ROS with catalase (H2O2) or mannitol (OH-)
      decreased the phagocytosis of myelin by macrophages, whereas superoxide dismutase
      (O2-) did not show this effect. In addition, Lipoic acid (LA), a non-specific
      scavenger of ROS, also decreased the phagocytosis of myelin by macrophages. In
      our results, we demonstrate for the first time that ROS appear to play a
      regulatory role in the phagocytosis of myelin.

PMID- 9916882
TI  - Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and
      IL-6 production by human blood mononuclear cells.
AB  - Many functional studies show that melatonin plays a fundamental role in
      neuroimmunomodulation. In this paper, we have extended our studies on the
      influence of melatonin on IL-2 and IL-6 production by human peripheral blood
      mononuclear cells (PBMCs) by comparing the effects of the specific membrane
      receptor agonist S 20098, the RZR/ROR(alpha) receptor agonist CGP 52608, and
      structurally related thiazolidinediones. Melatonin bound to membranes as well as
      to nuclei of human PBMCs with about the same affinity (IC50 values around 5 nM).
      S 20098 bound to PBMC membranes but not to PBMC nuclei, although the affinity was
      at least 100 times lower than that of melatonin; this compound did not stimulate
      cytokine production. In contrast, all four CGP compounds did not bind to PBMC
      membranes, while binding to nuclei exhibited IC50 values comparable to those of
      melatonin. The thiazolidinediones activating the RZR/ROR(alpha) receptor (CGP
      52608, CGP 53079) also increased IL-2 and IL-6 production. CGP 55644 had no
      effect on cytokine production and antagonized the effects of CGP 52608 on IL-2
      and IL-6 production; moreover, CGP 55644 decreased the enhanced IL-2 production
      caused by melatonin. Results obtained in monocyte cultures resembled closely
      those shown in PBMCs. The results reported in this paper confirm the involvement
      of a nuclear mechanism in the melatonin effects on cytokine production in human
      PBMCs. We have also shown a synergistic effect of S 20098 and CGP 52608,
      suggesting a possible link between nuclear and membrane melatonin receptors in
      PBMCs.

PMID- 9916883
TI  - The expression of cytokines and their receptors in normal and mildly reactive
      human brain.
AB  - There are many inflammatory diseases of the brain such as AIDS, other viral
      encephalitides and multiple sclerosis all of which are probably influenced by
      both systemic and focal CNS cytokine release. We have studied the expression of a
      wide range of pro- and anti-inflammatory cytokines and their receptors, beta2
      microglobulin, and MHC Class II, using immunocytochemistry on cryostat sections
      of normal and mildly reactive human brain. The aim was to try to determine the
      cytokine 'baseline' expression in normal human brain and the results obtained
      indicated very low expression of various cytokines and their receptors, mainly by
      microglia and macrophages with some endothelial expression.

PMID- 9916884
TI  - Acute and relapsing experimental autoimmune encephalomyelitis are regulated by
      differential expression of the CC chemokines macrophage inflammatory protein
      1alpha and monocyte chemotactic protein-1.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated
      disease of the central nervous system (CNS), characterized by mononuclear cell
      infiltration and demyelination resulting in paralysis. We examined CC chemokine
      expression in the CNS throughout the entire course of the disease and found that
      the production of macrophage inflammatory protein (MIP)-1alpha correlated with
      increasing acute disease severity and remained elevated throughout chronic,
      relapsing disease. In contrast, a substantial level of monocyte chemotactic
      protein (MCP)-1 expression was not observed until late in acute disease and
      continued to be evident in the relapsing phase of the disease. MCP-1 expression
      correlated with increasing severity of clinical relapses. Lower levels of RANTES
      in the CNS were noted throughout the disease course, but showed little
      correlation with either acute or relapsing disease. Although RANTES expression
      was observed during the entire course of disease, anti-RANTES treatment had no
      effect on clinical disease progression. Anti-MCP-1, but not anti-MIP-1alpha,
      treatment during relapsing EAE decreased clinical severity of relapsing disease.
      Furthermore, anti-MCP-1 treatment reduced CNS macrophage accumulation during
      relapsing EAE. These results suggest that MIP-1alpha controls mononuclear cell
      accumulation during acute EAE, while MCP-1 controls mononuclear cell infiltration
      during relapsing EAE.

PMID- 9916885
TI  - HLA-DRB1 and tumor necrosis factor gene polymorphisms in Japanese patients with
      multiple sclerosis.
AB  - We studied genetic polymorphisms in the tumor necrosis factor (TNF) region as
      well as HLA-DRB1 of 42 patients with Western-type multiple sclerosis (MS) and 38
      with Asian-type MS in Japan. The sex ratio (Female:Male) was significantly higher
      in Asian than in Western type MS (3.8 vs. 1.3, P = 0.038). The frequency of HLA
      DRB1 * 1501 allele in the Western-type MS group increased significantly compared
      with the control group, while Asian-type MS and control groups showed similar
      distribution in the frequencies of HLA-DRB1 alleles. No significant differences
      existed in the TNF region, however, including TNF-a microsatellite alleles. The
      results suggest that MS in Asians may present two different clinical and
      immunogenetic manifestations.

PMID- 9916886
TI  - Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating
      mechanisms of Th1 to Th2/Th3 immune-deviation.
AB  - The synthetic polypeptide copolymer-1 (Cop-1; Copaxone; Glatiramer Acetate) has
      been recently approved as an effective treatment in relapsing multiple sclerosis
      (MS). A large body of evidence demonstrates that Cop-1 induces active suppression
      of CNS-inflammatory disease in animal models. However, Cop-1-mediated suppressor
      mechanisms have not yet been elucidated in humans. A 12-month open study
      following clinical and immunological parameters of ten relapsing MS patients
      treated with Cop-1 is presented. Relapse rates and disability scores (EDSS) were
      evaluated prior to and after 12 months of treatment. The immunological parameters
      assessed prior to and at 3 months' interval during treatment included serum
      levels of soluble IL-2 receptor (sIL-2R) and IL-10 as well as leukocyte cytokine
      mRNA expression of TNF alpha, IL-4 and TGF-beta. Copaxone treatment was found to
      lead to a significant reduction in the mean annual relapse rate (from 1.4 prior
      to treatment to 0.6 during treatment) and stabilization of disability in 90% of
      the patients. The treatment was accompanied by an elevation of serum IL-10
      levels, suppression of the pro-inflammatory cytokine TNF alpha mRNA, and an
      elevation of the anti-inflammatory cytokines TGF-beta and IL-4 mRNAs in PBLs.
      These results suggest that the beneficial clinical effects of Copaxone in MS
      patients may be attributed to changes in activation of T cell subsets and a shift
      from Th1 to Th2/Th3 cytokine profile, probably leading to Cop-1-driven mechanisms
      of bystander suppression.

PMID- 9916887
TI  - CXC chemokines interleukin-8 (IL-8) and growth-related gene product alpha
      (GROalpha) modulate Purkinje neuron activity in mouse cerebellum.
AB  - We give here evidence that Purkinje neurons (PNs) of mouse cerebellar slices
      studied with patch clamp technique combined with laser confocal microscopy,
      respond to human IL-8 and GROalpha by (i) a cytosolic Ca2+ transient compatible
      with inositol (1,4,5) trisphosphate (InsP3) formation; (ii) an enhancement of the
      neurotransmitter release; and (iii) an impairment of the long-term depression of
      synaptic strength (LTD). It was also found the expression of IL-8 receptor type 2
      in PN and granule cells by immunofluorescence, immunoblotting and RT-PCR
      analysis. Considered together these findings suggest that IL-8 and GROalpha may
      play a neuromodulatory role on mouse cerebellum.

PMID- 9916888
TI  - An inhibitor of inducible nitric oxide synthase ameliorates experimental
      autoimmune myocarditis in Lewis rats.
AB  - We studied the effect of nitric oxide (NO) on experimental autoimmune myocarditis
      (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an
      enzyme that produces NO, on hearts affected with EAC, by testing the effects of
      aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western
      blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized
      cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions
      were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day)
      significantly reduced the incidence of EAC (p < 0.05) and ameliorated the
      histological score for the cardiac inflammation (p < 0.01) compared with the low
      dose AG (100 mg/kg/day) and vehicle treated groups. The immunoblot analysis
      showed that a high dose of AG effectively suppressed iNOS in hearts affected with
      EAC. An iNOS band was barely detected in the high dose AG (200 mg/kg) treated
      group, while it was distinctively visualized in the vehicle and low dose AG (100
      mg/kg) treated groups. These results suggest that iNOS is upregulated in EAC
      lesions and increased NO production plays an important role in the development of
      EAC. In addition, selective iNOS inhibitors may have a therapeutic role in
      treating certain autoimmune diseases including EAC.

PMID- 9916889
TI  - Restraint stress-induced immunosuppression by inhibiting leukocyte migration and
      Th1 cytokine expression during the intraperitoneal infection of Listeria
      monocytogenes.
AB  - In this study, a murine model of Listeria monocytogenes infection was used to
      investigate effects of restraint stress (RST) on host defense. We observed that
      the L. monocytogenes infection as well as RST induced an elevation of endogenous
      corticosterone (CORT) levels and RST synergistically enhanced endogenous CORT
      levels during the listerial infection. RST suppressed the migration of leukocytes
      including macrophages, neutrophils, NK cells and lymphocytes into the peritoneal
      cavities after the intraperitoneal inoculation of L. monocytogenes. RST also
      suppressed the increase of the surface MHC class II antigen expression in both
      peritoneal macrophages and B cells during the listerial infection. Interestingly,
      gene expression of iNOS, MCP-1 (JE) and Th1-type cytokines including IFN-gamma
      and IL-12 was down-regulated but Th2-type cytokine (IL-4 and IL-6) gene
      expression in the PEC was rather up-regulated on day 7 after infection,
      indicating that Th2-type immune response is more resistant to the elevated
      endogenous CORT levels than Th1-type response. Treatment of mice with RU486, a
      glucocorticoid receptor antagonist, restored the immune responses suppressed by
      RST to their normal levels in the infected mice, suggesting that the RST-induced
      elevation of endogenous corticosterone levels is mainly responsible for the
      induction of the immunosuppressive events during L. monocytogenes infection.

PMID- 9916890
TI  - HuR, a novel target of anti-Hu antibodies, is expressed in non-neural tissues.
AB  - Paraneoplastic encephalomyelitis (PEM) is characterized by a diverse set of
      clinical signs that are limited to the nervous system. The serologic hallmark of
      PEM is the presence of circulating autoantibodies, collectively referred to as
      'anti-Hu,' which immunoreact specifically with members of the Elav protein
      family. Until recently, the ELAV antigens were only detected in neurons, thus
      strongly supporting a role for anti-Hu antibodies in the selective neural tissue
      injury in PEM. The identification of HuR, however, a new member with a broad, non
      neural pattern of RNA expression, raises several fundamental questions regarding
      PEM. First, why are non-neural tissues spared in PEM? Second, why is PEM
      predominantly associated with neuroendocrine tumors? To begin addressing these
      questions, we sought to determine whether the antibody response to HuR differs
      from the neural-specific counterparts in patients with PEM, and to characterize
      the protein expression pattern of this novel antigen in peripheral tissues and
      tumors. Using sera from 11 patients with Hu-positive PEM, we found that the
      majority of samples (73%) were weakly or non-reactive for recombinant HuR on
      Western blot, in contrast to consistently strong immunoreactivity with the neural
      specific members HuD and Hel-N1. We also demonstrate that HuR is expressed at the
      protein level in both non-neural tissues and non-neuroendocrine tumors. These
      findings suggest that immunoreactive differences among Elav family members may
      contribute to the neural-restrictive pattern of tissue injury in patients with
      PEM.

PMID- 9916891
TI  - IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic
      mice carrying a null mutation for IL-6.
AB  - The role of interleukin-6 (IL-6) on emotional behavior was studied in two
      experiments using transgenic mice carrying a null mutation for IL-6 (IL-6(-/-)).
      In the first experiment, IL-6(-/-) mice were compared with the two wild-type
      strains contributing to the genetic background of the transgenic mice, namely
      C57BL/6J and 129/SvJ, as well as with the F2 offspring of C57BL/6J x 129/SvJ
      mice. The two parental strains differed substantially in terms of emotional
      reactivity, suggesting that the F2 offspring were more appropriated for analyzing
      the effect of the null mutation. IL-6(-/-) mice showed lower levels of ambulation
      in the holeboard, and lower levels of exploration of the open arms of the plus
      maze, than the wild-type F2 C57BL/6J x 129/SvJ mice. In the second experiment, IL
      6(-/-) mice were backcrossed for 10 generations to C57BL/6J mice to decrease the
      uncertainty of the effect of the genetic background, and when compared with wild
      type C57BL/6J mice in the holeboard and the plus-maze, the same results were
      obtained. Therefore, IL-6(-/-) mice seem to be more emotional than their
      appropriate controls, suggesting that the major cytokine IL-6 is involved in the
      control of emotionality.

PMID- 9916893
TI  - A novel rat CC chemokine, identified by targeted differential display, is
      upregulated in brain inflammation.
AB  - A novel rat chemokine, termed ST38, was identified through its upregulation in
      ischemic brain tissue using a biased differential display technique targeting
      mRNAs with regulatory AUUUA-motifs typically found in transcripts of cytokine and
      immediate early genes. ST38 transcripts were transiently induced in ischemic
      cortex between 4 and 24 h after middle cerebral artery occlusion. ST38 is a
      member of the CC chemokine family, closely related to human Exodus-1. The gene of
      the mouse ST38 homologue was mapped to the central region of chromosome 1. In
      experimental autoimmune panencephalomyelitis ST38 expression correlated with the
      onset of inflammation and was significantly reduced by TNF-neutralization in
      vivo. Inflammatory stimuli induce ST38 transcription in astrocyte, microglia and
      macrophage cultures. These findings suggest a role of ST38 in the control of
      neuroinflammatory tissue responses.

PMID- 9916892
TI  - Protein kinase C-mediated regulation of inducible nitric oxide synthase
      expression in cultured microglial cells.
AB  - Nitric oxide (NO) has been implicated in a number of important brain functions,
      such as long-term potentiation (LTP) and long-term depression (LTD), and in
      events associated with neurodegeneration and neuroprotection. In response to
      brain injury or disease NO production is increased by an inducible enzyme (iNOS),
      which is only expressed under these conditions. Activated microglia are a major
      cellular source of iNOS in brain. Due to the important role of iNOS in brain
      injury and disease, a detailed understanding of intracellular events triggering
      the expression of iNOS in microglia would facilitate pharmacotherapeutic
      approaches. It is shown here, that iNOS mRNA, protein and NO product are induced
      in cultured microglia by lipopolysaccharide (LPS). This induction is reduced by a
      number of substances elevating intracellular cyclic AMP levels. It is unabated,
      however, in the presence of substances inhibiting cyclooxygenase-1 and/or
      cyclooxygenase-2 (e.g., acetyl salicylic acid, SC 58125, L 745337), but is
      decreased by approx. 50% with PDTC, a scavenger of reactive oxygen intermediates
      (ROI) that inhibits nuclear factor kappaB (NF-kappaB) activation. Furthermore,
      inhibitors of protein kinase C (PKC) strongly inhibit iNOS mRNA and protein
      induction. PKC, therefore, constitutes a major second messenger component
      (besides NF-kappaB) in the signaling pathway regulating iNOS expression in
      microglia.

PMID- 9916894
TI  - Labeling of dopamine D3 and D4 receptor subtypes in human peripheral blood
      lymphocytes with [3H]7-OH-DPAT: a combined radioligand binding assay and
      immunochemical study.
AB  - Molecular biology studies have demonstrated that human peripheral blood
      lymphocytes express dopamine D2-like receptors belonging to the D3 and D4
      receptor subtypes, whereas the characterization of these receptors using
      radioligand binding assay techniques provided conflicting results. The
      preferential dopamine D3 receptor agonist [3H]7-hydroxy-N, N-di-n-propyl-2
      aminotetralin ([3H]7-OH-DPAT) was used recently for labeling lymphocyte dopamine
      D3 receptor. However, the selectivity of this compound for the D3 receptor was
      questioned. In this study we have investigated human peripheral blood lymphocyte
      dopamine receptor subtypes labeled by [3H]7-OH-DPAT using a conventional
      radioligand binding assay technique and antibodies against dopamine D2-like
      receptor subtypes. [3H]7-OH-DPAT was specifically bound to intact human
      peripheral blood lymphocytes with a dissociation constant (Kd) value of 0.32 +
      0.03 nM and a maximum density of binding sites (Bmax) of 18.2 + 0.8 fmol/2 x
      10(6) cells. [3H]7-OH-DPAT binding was unaffected by antibodies against dopamine
      D2 and D2S receptors. Anti-dopamine D3 and D4 receptor antibodies reduced [3H]7
      OH-DPAT binding by about 53% and 32% respectively. Combination of anti D3 and D4
      receptor antibodies reduced remarkably [3H]7-OH-DPAT binding. The above results
      suggest that the dopamine receptor agonist [3H]7-OH-DPAT labels dopamine D3 and
      D4 receptor subtypes in human peripheral blood lymphocytes. The use of antibodies
      raised against dopamine receptor subtypes in combination with radioligand binding
      assay may contribute to define receptor subtypes expressed by human peripheral
      blood lymphocytes in health and disease.

PMID- 9916895
TI  - Transcriptional regulation of intercellular adhesion molecule-1 in astrocytes
      involves NF-kappaB and C/EBP isoforms.
AB  - ICAM-1 is an inducible cell surface protein that is involved in cell
      extravasation into inflamed tissues as well as immune responses. ICAM-1
      expression is upregulated by proinflammatory cytokines such as TNF-alpha and IL
      1beta in numerous cell types including the astrocyte, which functions as an
      immune effector cell in the central nervous system (CNS). We investigated the
      mechanism by which the ICAM-1 gene is transcriptionally regulated in astrocytes
      in response to TNF-alpha and IL-1beta. Human ICAM-1 promoter constructs linked to
      the reporter gene luciferase were transiently transfected into astrocytes,
      stimulated with TNF-alpha and IL-1beta, and ICAM-1 promoter activity examined. We
      determined that binding sites for both NF-kappaB (-186 bp region) and C/EBP (-198
      bp region) are involved in TNF-alpha and IL-1beta-mediated ICAM-1 upregulation.
      Electrophoretic mobility shift assays using antibodies against NF-kappaB and
      C/EBP isoforms showed that p65 homodimers and p65/p50 heterodimers bind to the NF
      kappaB site, and C/EBPdelta homodimers and C/EBPbeta/delta heterodimers bind to
      the C/EBP site. Transient transfection assays demonstrated that overexpression of
      p65 could transactivate the promoter activity of ICAM-1 reporter constructs. p50
      overexpression had no effect on the basal levels of ICAM-1 transcription, but
      inhibited, in a dose dependent manner, p65 mediated transcription. Overexpression
      of C/EBPbeta slightly inhibited basal levels of ICAM-1 promoter activity,
      however, when C/EBPbeta and p65 were cotransfected, C/EBPbeta completely
      abolished the transactivating effects of p65. These results demonstrate that
      cytokine-induced ICAM-1 expression in astrocytes is regulated by interactions
      between NF-kappaB and C/EBP transcription factors.

PMID- 9916896
TI  - No evidence for interleukin-4 gene conferring susceptibility to myasthenia
      gravis.
AB  - A variable number of tandem repeat (VNTR) and a dinucleotide repeat polymorphism
      in IL-4 gene were examined in Swedish myasthenia gravis (MG) patients and
      ethnically matched healthy individuals. There were no associations between these
      polymorphisms and MG patients as a whole group or stratified by clinical and
      pathological parameters and genetic markers in MHC gene (TNF-alpha NcoI allele 2)
      and IL-1 gene (IL-1beta TaqI allele 2). This lack of association between the IL-4
      gene and disease contrasts to our previous results showing that MG is associated
      with higher secretor phenotypes of two prototype proinflammatory cytokine (TNF
      alpha and IL-1) genes.

PMID- 9916897
TI  - Classification of fluoroquinolones.

PMID- 9916898
TI  - WHO alliance for the global elimination of blinding trachoma and the potential
      use of azithromycin.

PMID- 9916899
TI  - Imipenem versus targeted therapy in cancer patients.
AB  - In many instances, broad-spectrum antibiotics are initiated empirically in
      febrile cancer patients and continued for the whole duration of therapy. An
      alternative is to narrow the spectrum whenever the offending pathogen is
      identified. This study is aimed at comparing these two options. Non-neutropenic
      cancer patients with severe infections received empiric imipenem. After 72 h,
      those with microbiologically documented infection were randomized either to
      continue imipenem or to receive a targeted therapy. After 72 h of imipenem 76.1%
      were improved. After randomization, a higher efficacy was observed with imipenem
      (88.5 vs. 72.1%: P = 0.025). Bacterial and fungal superinfections were
      comparable. Costs were lower for targeted therapy in gram-positive infection and
      higher in gram-negative infection.

PMID- 9916900
TI  - Clinical relevance of a European collaborative study on comparative
      susceptibility of gram-positive clinical isolates to teicoplanin and vancomycin.
AB  - Seventy laboratories in nine European countries (Belgium, France, Germany, Italy,
      The Netherlands, Portugal, Spain, Switzerland and the UK) each collected 100
      consecutive gram-positive bacterial pathogens during 1995. MICs were determined
      by a co-ordinating laboratory in each country using an agar incorporation method
      with Mueller Hinton medium (NCCLS). Quality control was ensured by distribution
      of five test strains to the co-ordinating laboratories. A total of 7078 isolates
      was collected: 2885 Staphylococcus aureus, 1706 enterococci, 1480 coagulase
      negative staphylococci (CNS), 932 Streptococcus spp. (including 289 strains of S.
      pneumoniae) and 75 miscellaneous species. Of these, the country coordinators
      successfully re-tested 6824 isolates. Using NCCLS interpretive criteria, overall
      39 isolates (including 28 strains of enterococci) were teicoplanin-resistant
      (0.57%) and 38 (mostly CNS; 0.56%) were intermediate, whilst 32 isolates
      (including 30 strains of enterococci) were resistant to vancomycin (0.47%) and 7
      (all enterococci; 0.10%) were intermediate. The overall resistance rate was < or
      = 0.5%. The two glycopeptides were essentially active against the major pathogens
      encountered in the survey. The only real difference with clinical implications
      from previously reported susceptibility data is the emergence and spread of
      resistance in enterococci, particularly in E. faecium. Resistance was highest in
      SSTI, UTI, bloodstream and GI infections; no resistance was encountered in RTI,
      gynaecological infections or central nervous system infections. This resistance
      was also geographically diverse: Resistance to vancomycin in E. faecalis was
      present only in France, Germany, Italy, Portugal and Spain (Italy and Spain only
      for teicoplanin), whilst resistance to teicoplanin and vancomycin in E. faecium
      was present in all countries except Spain. Eight isolates (0.5% of all
      enterococci) were vancomycin-resistant but teicoplanin-susceptible, exhibiting
      the vanB phenotype. These were four strains of E. faecalis and four strains of E.
      faecium. Whilst isolates of S. haemolyticus had higher MIC of teicoplanin than
      other CNS, and were more susceptible to vancomycin, overall resistance to
      teicoplanin was low (3.3% in S. haemolyticus; 0.6% in CNS). S. haemolyticus was a
      relatively rare pathogen, accounting for 6.3% of all CNS isolates, and 1.4% of
      all gram-positives collected. The results of this survey show that, despite
      occasional nosocomial problems (e.g. with enterococci and S. haemolyticus),
      teicoplanin or vancomycin remain adequate therapy for infections caused by gram
      positive pathogens in the 1990s.

PMID- 9916901
TI  - Comparison of bactericidal activity after multidose administration of
      clarithromycin, azithromycin, and ceruroxime axetil against Streptococcus
      pneumoniae.
AB  - The objective of this study was to compare the duration of serum bactericidal
      activity (SBA) for clarithromycin, azithromycin, and cefuroxime axetil in 12
      young healthy volunteers after 5 days of therapy (dosed to steady-state) against
      two strains each of penicillin (PCN)-susceptible, -intermediate, and -resistant
      Streptococcus pneumoniae. This was a randomized, 3-way crossover study. All
      isolates were susceptible to clarithromycin (MICs 0.125 mg/l) and azithromycin
      (MICs 0.25-0.5 mg/l), while cefuroxime axetil susceptibilities correlated with
      PCN. Results showed that SBA was maintained for 100% of the dosing interval for
      clarithromycin and 50-100% for azithromycin regardless of PCN susceptibility when
      standard doses were employed. Cefuroxime axetil was active only against the PCN
      susceptible isolate for 50% of the dosing interval, indicating that it should
      only be used for PCN-susceptible S. pneumoniae.

PMID- 9916902
TI  - Bactericidal activity of lansoprazole and three macrolides against Helicobacter
      pylori strains tested by the time-kill kinetic method.
AB  - The bactericidal activities of macrolides (clarithromycin, roxithromycin and
      azithromicyn) and lansoprazole, alone and in combination, against Helicobacter
      pylori strains were evaluated. It was found that the association of lansoprazole
      and clarithromycin resulted in a marked synergism, while the combination of
      roxithromycin or azithromycin with lansoprazole had synergistic and additive
      effects.

PMID- 9916903
TI  - Antifungal susceptibility of Candida isolates at the American University of
      Beirut Medical Center.
AB  - For the first time from Lebanon, the antifungal susceptibility patterns of 70
      consecutive clinical candida isolates (each from one patient) representing 48 C.
      albicans, 12 C. tropicalis, 6 C. parapsilosis, 2 C. kruseii, and 2 C.
      (Torulopsis) glabrata were studied against amphotericin B (AP), 5-fluorocytosine
      (FC), ketoconazole (KE), fluconazole (FL), and itraconazole (IT) using the
      Epsilometer test (E-test; AB Biodisk, Solna, Sweden). The MIC90 (and MIC range,
      mg/l) determined, at 24 h incubation, for each antifungal agent against C.
      albicans were: AP 0.032 (< or = 0.002-0.064), FC 0.75 (0.023-2), KE 0.064 (0.002-
      > 32), FL 2 (0.064- > 256), and IT 0.19 (0.012-2), against C. tropicalis were: AP
      0.016 (< 0.002-0.047), FC 0.125 (0.023-0.19), KE 0.094 (0.012-0.19), FL 2 (0.5
      2), and IT 0.5 (0.047-1) and against C. parapsilosis were: AP < 0.002 (< 0.002
      0.002), FC 0.047 (0.003-0.5), KE 0.004 (0.002-0.004), FL 0.125 (0.032-0.19), and
      IT 0.004 (< 0.002-0.004). Based on the NCCLS established MICs breakpoints,
      resistance was found among C. albicans to FL (MIC > or = 6 mg/l) and IT (MIC > or
      = 1 mg/l) in 6 and 4%, respectively, and among C. tropicalis to IT in 17% of the
      isolates. The susceptibility dependent upon dose (S-DD) was noted only to IT (MIC
      0.25-0.5 mg/l) among C. albicans (8%) and C. tropicalis (58%). MICs determination
      at 48 h incubation were higher, showed more resistance rates and more endpoint
      trailing particularly with the azoles drugs. The small numbers of C. kruseii and
      C. glabrata preclude providing meaningful results. Thus, this study indicates
      that the antifungal susceptibility by E-test can be conveniently incorporated and
      performed in a hospital-based clinical laboratory. Despite the uniform
      susceptibility to AP and FC, resistance to azoles drugs is encountered in a range
      of 4-17% among candida isolates in this country.

PMID- 9916904
TI  - Canadian Pseudomonas aeruginosa susceptibility study from 48 medical centers:
      focus on ciprofloxacin.
AB  - We tested 1503 clinical isolates of Pseudomonas aeruginosa, from 48 Canadian
      medical centers, against ciprofloxacin and 11 other antimicrobial agents to
      determine in vitro activity. The frequency of susceptibility was highest for
      carbenicillin and ticarcillin (91% each) followed by imipenem and ceftazadime
      (90% each). Overall susceptibility (< or = 1.0 mg/l) to ciprofloxacin was 84%
      while resistance (> or = 4.0 mg/l) was 12%. Ciprofloxacin resistant isolates were
      more common from urinary tract specimens than from specimens collected from the
      respiratory and/or skin and soft tissue. Isolates from cystic fibrosis patients
      were more resistant to all agents tested than isolates from non-cystic fibrosis
      patients.

PMID- 9916905
TI  - Susceptibility patterns of Enterococcus spp. isolated in Poland during 1996.
AB  - Susceptibility of Enterococcus spp. isolated from various clinical specimens to
      different antimicrobial agents was evaluated. Of the 346 enterococcal isolates
      obtained from four regional Polish hospitals during 6 months of 1996, 261 (75.4%)
      were identified as Enterococcus faecalis, 75 (21.7%) as Enterococcus faecium and
      ten (2.9%) as other enterococcal species. High-level resistance to gentamicin was
      expressed by 33.4% of E. faecalis and 86.5% of E. faecium strains and
      corresponding streptomycin resistance by 43.9 and 82.4%, respectively. Over 80%
      of E. faecium isolates were resistant to ampicillin. None of the isolates was
      resistant to teicoplanin, however 7.9% of E. fecalis and 1.4% of E. faecium
      strains were moderately susceptible to vancomycin.

PMID- 9916906
TI  - Typing of consecutive methicillin-resistant Staphylococcus aureus isolates from
      intensive care unit patients and staff with pulsed-field gel electrophoresis.
AB  - Six consecutive methicillin-resistant Staphylococcus aureus (MRSA) isolates
      obtained in a 2-month period from tracheal aspirates of six intensive care unit
      (ICU) patients with nosocomial pneumonia and two MRSA isolates from nasal
      carriers among staff were typed to determine whether one or more strains were
      involved and whether nasal carriage was the source of the outbreak. Pulsed-field
      gel electrophoresis (PFGE) of chromosomal DNA was used to type MRSA isolates. The
      typing showed that the outbreak was caused by a single epidemic MRSA clone. The
      MRSA strain isolated from the staff was unrelated to the outbreak strain and was
      therefore not the source of the outbreak in this study. The source was apparently
      the index patient followed by transfer of MRSA to other patients on medical
      equipment or on the hands of staff who did not adhere strictly to infection
      control measures.

PMID- 9916908
TI  - Antibacterial activity of human pleural fluid: alone and in combination with
      antibiotics.
AB  - This study investigated the antibacterial activity of human pleural fluid (HPF)
      and its interaction with gentamicin (GM), meropenem (MRPM), ciprofloxacin (CPFX)
      and clarithromycin (CLTM) against Escherichia coli K-12, Proteus rettgeri
      (Sanelli) and Staphylococcus aureus. Minimal inhibitory concentrations or
      volumes, expressed as MIC or volume percentage (MIV, V/V%), were measured using a
      micro-dilution technique in microtiter plates. The antimicrobial activity of HPF
      combinations with antimicrobial drugs was evaluated by the chequerboard method
      calculating the fractional inhibitory concentration index (FIC) values. HPF MIVs
      (%) were: 37.54; 19.85; 1.74 for E. coli, P. rettgeri and S. aureus,
      respectively. FIC values indicated a synergistic effect with GM, MRPM and CPFX
      against E. coli and P. rettgeri and an additive effect for the combination HPF
      plus CLTM or indifference with HPF plus GM and CPFX against S. aureus. The
      presence of antibodies, complement factors, lysozyme, alpha-defensins and enzymes
      could explain the antimicrobial activity of HPF and its synergistic effect with
      certain antibiotics.

PMID- 9916907
TI  - Aetiology, cost of antimicrobial therapy and outcome in neutropenic patients who
      developed bacteraemia during antimicrobial prophylaxis: a case-control study.
AB  - Sixty four episodes of bacteraemia that appeared during antimicrobial prophylaxis
      with an oral quinolone plus an azole in neutropenic cancer patients were compared
      with 128 cases of bacteraemia in a cohort of controls matched for age, sex,
      underlying disease, neutropenia and vascular catheter in situ to assess
      differences in aetiology, cost of therapy and outcome. Patients who received
      prophylaxis had breakthrough bacteraemias of a different aetiology compared with
      the control group: they had significantly fewer multiply-resistant strains (21.9
      vs. 51.5, P < 0.04) and a longer afebrile neutropenic period (9.55 days vs. 4.1,
      P < 0.001). Patients who received prophylaxis also had bacteraemias that were
      significantly more frequently caused by viridans streptococci (9.4%, vs. 1.7%, P
      < 0.01), enterococci (15.6% vs. 7.2%, P < 0.05) and Stenotrophomonas maltophilia
      (17.2% vs. 3.4%, P < 0.01). The cost of antimicrobial therapy per case (37401 SKK
      (1091 USD) vs. 31808 SKK (899 USD), P < 0.05) was also significantly higher in
      cases than controls; however, the number of administered antibiotics (4.18 vs.
      3.21 per case, P = NS) was similar in both groups. There were no differences in
      outcome between both groups. However patients who received prophylaxis had
      significantly longer periods of afebrile neutropenia (9.55 days vs. 4.1, P <
      0.001) and bacteraemia developed later than in controls. Also, the incidence of
      polymicrobial bacteraemia caused by multiresistant strains was lower among cases
      (21.9 vs. 51.5, P < 0.04).

PMID- 9916909
TI  - Comparative anti-anaerobic activity of Men 10700, a penem antibiotic.
AB  - The in vitro activity of Men 10700, a new penem, has been compared with that of
      metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third
      generation cephalosporins against 120 strains of anaerobes. The organisms tested
      comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis
      and speciated members of the genera Fusobacterium, Veillonella and
      Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and
      was more potent than metronidazole against all species except C. difficile and P.
      anaerobius. The spectrum of activity of Men 10700 suggests this agent may be
      useful for treating infections caused by anaerobes.

PMID- 9916911
TI  - Advances in molecular hematopathology: T-cell receptor gamma and bcl-2 genes.

PMID- 9916910
TI  - The tauopathies: toward an experimental animal model.

PMID- 9916912
TI  - A novel amyloidogenic variant of apolipoprotein AI: implications for a
      conformational change leading to cardiomyopathy.

PMID- 9916913
TI  - Combined morphological and interphase fluorescence in situ hybridization study in
      multiple myeloma of Chinese patients.
AB  - To gain insight into the real incidence of the numeric chromosomal aberrations
      and the cell lineage involvement of the neoplastic process in multiple myeloma
      (MM), we examined 18 Chinese MM patients by May-Grunwald-Giemsa (MGG) staining
      and fluorescence in situ hybridization using three DNA centromeric probes
      specific for chromosomes 3, 7, and 9. In this investigation, cytogenetic
      abnormalities were detected in plasma cells (PCs), myeloid cells (MCs), and
      lymphoid cells (LCs) in all of the MM patients studied. This is the first
      demonstration of the cytogenetic aberration involved in the myeloid series.
      Furthermore, the MCs and PCs of 16 MM patients had the same aneuploidies in one
      or more of the chromosomes analyzed. These data suggest that the neoplastic
      transformation of MM may occur early in the hematopoietic development.
      Chromosomal aberrations involving mainly subclones and considerable cellular
      heterogeneity with gain of a variety of copy numbers of the same chromosome were
      demonstrated within PCs, which may possibly be the result of an underlying defect
      of PCs in the control of their number of chromosomes. Whereas PCs showed evidence
      suggestive of increased polyploidization, MCs and LCs, which exhibited similar
      chromosomal patterns as the former, rarely did. Thus, the clonal evolution from
      LC to PC, if that happens in MM, is characterized by chromosomal instability
      favoring growth of tumor cells with polysomies and polyploidies.

PMID- 9916914
TI  - Embryonic form of smooth muscle myosin heavy chain (SMemb/MHC-B) in
      gastrointestinal stromal tumor and interstitial cells of Cajal.
AB  - Myosin heavy chain (MHC) isoform expression was evaluated by immunohistochemistry
      and reverse transcription polymerase chain reaction (RT-PCR) to clarify a
      possible link between gastrointestinal stromal tumor (GIST) and interstitial
      cells of Cajal (ICCs) in the gastrointestinal (GI) tract. Using monoclonal
      antibodies against MHC isoforms, 18 of 27 GISTs (67%) showed immunoreactivity for
      non-smooth-muscle myosin or the embryonic form of MHC (SMemb), but only one tumor
      showed immunoreactivity for smooth muscle cell (SMC)-specific isoforms (SM1 and
      SM2). Co-expression of KIT or CD34, which is also expressed in GIST and ICCs, was
      demonstrated in 18 (100%) and 16 SMemb-positive tumors (89%), respectively.
      Otherwise, the expression of SMemb in GIST was not correlated with the patient's
      age or sex, tumor size, histological grade of GIST, or expression of mesenchymal
      cell markers, such as alpha-smooth muscle actin (alpha-SMA) or S100 protein. By
      double-fluorescence immunostaining of the tunica muscularis of the GI tract wall,
      co-expression of KIT, CD34, and SMemb was demonstrated in ICCs, which were
      negative for SM1 and SM2. RT-PCR analysis confirmed that GIST expressed SMemb
      mRNA, which lacked neuronal cell-specific inserts of 30 bp. These facts further
      strengthen the current hypothesis that GIST is a tumor of ICCs.

PMID- 9916915
TI  - Restricted high level expression of Tcf-4 protein in intestinal and mammary gland
      epithelium.
AB  - Tcf-4 is a member of the Tcf/Lef family of transcription factors that interact
      functionally with beta-catenin to mediate Wnt signaling in vertebrates. We have
      previously demonstrated that the tumor suppressor function of APC in the small
      intestine is mediated via regulation of Tcf-4/beta-catenin transcriptional
      activity. To gain further insight into the role of Tcf-4 in development and
      carcinogenesis we have generated several mouse monoclonal antibodies, one of
      which is specific for Tcf-4 and another of which recognizes both Tcf-3 and Tcf-4.
      Immunohistochemistry performed with the Tcf 4- specific monoclonal antibody
      revealed high levels of expression in normal intestinal and mammary epithelium
      and carcinomas derived therefrom. Additional sites of Tcf-3 expression, as
      revealed by staining with the Tcf-3/-4 antibody, occurred only within the stomach
      epithelium, hair follicles, and keratinocytes of the skin. A temporal Tcf-4
      expression gradient was observed along the crypt-villus axis of human small
      intestinal epithelium: strong Tcf-4 expression was present within the crypts of
      early (week 16) human fetal small intestine, with the villi showing barely
      detectable Tcf-4 protein levels. Tcf-4 expression levels increased dramatically
      on the villi of more highly developed (week 22) fetal small intestine. We
      conclude that Tcf-4 exhibits a highly restricted expression pattern related to
      the developmental stage of the intestinal epithelium. The high levels of Tcf-4
      expression in mammary epithelium and mammary carcinomas may also indicate a role
      in the development of this tissue and breast carcinoma.

PMID- 9916916
TI  - Assessment of genetic changes in hepatocellular carcinoma by comparative genomic
      hybridization analysis: relationship to disease stage, tumor size, and cirrhosis.
AB  - Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is
      prevalent in Southeast Asia. Although the etiological factors associated are now
      well recognized, the interactions between individual factors and the molecular
      mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on
      HCC has been limited because of poor hepatocyte growth in vitro. The recently
      developed technique of comparative genomic hybridization (CGH), however, permits
      screening of the entire genome without the need of cell culture. CGH was applied
      to the study of genomic aberrations in 67 surgically resected samples of HCC, 3
      of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver
      surrounding the tumors. All samples were from patients of a racially and
      etiologically homogeneous population in Southern China, where chronic hepatitis B
      virus infection is the main etiological factor. CGH analysis of the HCC samples
      revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases,
      48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q
      (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67
      cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this
      aberration was associated with the development of HCC. Genomic abnormalities were
      detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues
      surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases
      as T2, and 11 cases as T3. No significant difference in the pattern of genomic
      imbalances was detected between stages T2 and T3. A significant copy number loss
      of 4q11-q23 was, however, identified in those tumors larger than 3 cm in
      diameter. Of particular interest was the identification of 8q copy number gain in
      all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55
      cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation
      is likely associated with a growth advantage and proliferative stimulation that
      have encouraged malignant changes in the noncirrhotic human liver.

PMID- 9916917
TI  - Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis
      lesions.
AB  - The pathology of multiple sclerosis (MS) is characterized by breakdown of the
      blood-brain barrier (BBB), accompanied by infiltration of macrophages and T
      lymphocytes into the central nervous system (CNS). The migration of these cells
      into the CNS parenchyma may be partly regulated by chemokines. The aim of this
      study was therefore to investigate the cellular localization of the potent
      monocyte- and T-cell-attracting chemokine monocyte chemoattractant protein (MCP)
      1 by immunohistochemistry on postmortem brain tissue from MS and normal control
      cases. Brain tissue samples of six MS patients and four patients without a
      history of brain disease were neuropathologically classified according to
      characteristic (immuno)histochemical staining patterns. Frozen tissue sections of
      active demyelinating MS lesions, chronic active demyelinating MS lesions, and
      normal control brain were immunohistochemically stained with a monoclonal
      antibody directed against MCP-1. In active demyelinating MS lesions as well as in
      chronic active MS lesions, reactive hypertrophic astrocytes were strongly
      immunoreactive for MCP-1, whereas perivascular and parenchymal foamy macrophages
      did not express MCP-1 protein. These results suggest a significant role for the
      beta-chemokine MCP-1, synthesized in vivo by reactive hypertrophic astrocytes, in
      the recruitment and activation of myelin-degrading macrophages and thereby
      contributing to the evolution of MS lesions.

PMID- 9916918
TI  - Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign
      gastrointestinal stromal tumors and do not occur in leiomyomas or
      leiomyosarcomas.
AB  - Gastrointestinal stromal tumors (GISTs) comprise the largest subset of
      mesenchymal tumors of the gastrointestinal tract. These neoplasms differ
      histologically and immunohistochemically from typical leiomyomas and
      leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not
      desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been
      shown in five solitary GISTs and in tumors and leukocytes from a family with
      multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was
      detected in these cases. Stable transfection of the mutant c-kit complementary
      DNA was also shown to induce malignant transformation of murine lymphoid cells,
      suggesting that the c-kit mutations contribute to tumor development. In this
      study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the
      exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one
      benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3
      leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an
      in-frame deletion of 3-21 bp in all 13 GISTs with mutant bands. Wild-type bands
      from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant
      bands were cloned and sequenced. Additional mutations were found in 3 malignant
      and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4
      leiomyosarcomas. The mutation status of exon 11 did not correlate with
      immunohistochemically detectable expression of the CD117, as virtually all GISTs
      with or without such mutations showed CD117 immunoreactivity. The c-kit mutations
      occur preferentially in malignant GISTs and might be a clinically useful adjunct
      marker in the evaluation of GISTs. The conservation of the c-kit mutation
      pattern, observed in consecutive lesions from the same patients, suggests that
      these mutations might be useful tumor markers in monitoring recurrence or minimal
      residual disease.

PMID- 9916919
TI  - Immuno-LCM: laser capture microdissection of immunostained frozen sections for
      mRNA analysis.
AB  - Microdissection of routinely stained or unstained frozen sections has been used
      successfully to obtain purified cell populations for the analysis of cell
      specific gene expression patterns in primary tissues with a complex mixture of
      cell types. However, the precision and usefulness of microdissection is
      frequently limited by the difficulty to identify different cell types and
      structures by morphology alone. We therefore developed a rapid immunostaining
      procedure for frozen sections followed by laser capture microdissection (LCM) and
      RNA extraction, which allows targeted mRNA analysis of immunophenotypically
      defined cell populations. After fixation, frozen sections are immunostained under
      RNAse-free conditions using a rapid three-step streptavidin-biotin technique,
      dehydrated and immediately subjected to LCM. RNA is extracted from captured
      tissue, DNAse I treated, and reverse transcribed. Acetone-, methanol-, or
      ethanol/acetone-fixed sections give excellent immunostaining after 12 to 25
      minutes total processing time. Specificity, precision, and speed of
      microdissection is markedly increased due to improved identification of desired
      (or undesired) cell types. The mRNA recovered from immunostained tissue is of
      high quality. Single-step PCR is able to amplify fragments of more than 600 bp
      from both housekeeping genes such as beta-actin as well as cell-specific messages
      such as CD4 or CD19, using cDNA derived from less than 500 immunostained,
      microdissected cells. Immuno-LCM allows specific mRNA analysis of cell
      populations isolated according to their immunophenotype or expression of function
      related antigens and significantly expands our ability to investigate gene
      expression in heterogeneous tissues.

PMID- 9916920
TI  - Detection of clonal T-cell receptor gamma gene rearrangements in paraffin
      embedded tissue by polymerase chain reaction and nonradioactive single-strand
      conformational polymorphism analysis.
AB  - The diagnosis of T-cell lymphoproliferative disorders, which frequently involve
      the skin and other extranodal sites, is often problematic because of the
      difficulty in establishing clonality in paraffin-embedded tissue. To this end, we
      developed a simple, nonradioactive method to detect T-cell receptor gamma (TCR
      gamma) gene rearrangements by polymerase chain reaction single-strand
      conformational polymorphism (PCR-SSCP) in paraffin-embedded tissue. Jurkat and
      HSB-2 cell lines and peripheral blood samples from normal individuals were used
      as monoclonal and polyclonal controls, respectively. DNA was extracted from 24
      biopsies of T-cell lymphomas, 12 biopsies of reactive lymphoid infiltrates, and 2
      biopsies of primary cutaneous large B-cell lymphomas. Vgamma1-8, Vgamma9,
      Vgamma10, Vgamma11, and Jgamma1/Jgamma2 consensus primers were used for TCR-gamma
      gene rearrangement amplification and PCR products were analyzed by nonradioactive
      SSCP. Monoclonal controls yielded a well-defined banded pattern, whereas all
      polyclonal T-cell controls showed a reproducible pattern of smears. We detected
      monoclonality in 20/21 (95%) T-cell lymphoma cases, whereas no dominant T-cell
      clones were found in any of the reactive lymphoid infiltrates or B-cell
      lymphomas. Sensitivity of 1-5% was demonstrated by serially diluting Jurkat cells
      in mononuclear blood cells from normal individuals. We conclude that
      nonradioactive PCR-SSCP for TCR-gamma gene rearrangement analysis is a useful
      adjunct to routine histological and immunophenotypic methods in the diagnosis of
      T-cell lymphoproliferative disorders in paraffin-embedded tissue.

PMID- 9916921
TI  - NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded
      tissue.
AB  - CD10 (CALLA) antigen is expressed in a wide variety of epithelial and
      nonepithelial tissues, but its most significant application is in the diagnosis
      and classification of certain types of malignant lymphoma and leukemia. CD10 is
      expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL),
      follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although
      the antigen is not lineage specific, CD10 expression is widely used to define
      subgroups within B-ALL and is a useful tool for detecting the presence of
      leukemic blasts in the bloodstream. Currently available monoclonal antibodies to
      CD10 have been found to be effective only in fresh-frozen tissue and for
      techniques such as flow cytometry. We have used a recombinant protein
      corresponding to the whole of CD10 to generate a monoclonal antibody that is
      effective in paraffin-embedded tissue sections. We have used this antibody to
      assay for the presence of CD10 on a range of normal and pathological tissues.
      Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli,
      syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle
      center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We
      believe that this antibody will be of value in the characterization of malignant
      lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and
      subtyping of lymphoblastic leukemia, as well as the investigation of the
      significance of expression of CD10 in other normal and pathological tissues.

PMID- 9916922
TI  - Multiple mutation analyses in single tumor cells with improved whole genome
      amplification.
AB  - Combining whole genome amplification (WGA) methods with novel laser-based
      microdissection techniques has made it possible to exploit recent progress in
      molecular knowledge of cancer development and progression. However, WGA of one or
      a few cells has not yet been optimized and systematically evaluated for samples
      routinely processed in tumor pathology. We therefore studied the value of
      established WGA protocols in comparison to an improved PEP (I-PEP) PCR method in
      defined numbers of flow-sorted and microdissected tumor cells obtained both from
      frozen as well as formalin-fixed and paraffin-embedded tissue sections. In
      addition, the feasibility of I-PEP-PCR for mutation analysis was tested using
      clusters of 50-100 unfixed tumor cells obtained by touch preparation of ten
      breast carcinomas by conventional sequencing of exon 7 and 8 of the p53 gene.
      Finally, immunocytochemically stained microdissected single disseminated tumor
      cells from bone marrow aspirates were investigated with respect to mutations in
      codon 12 of Ki-ras by restriction fragment length polymorphism (RFLP)-PCR after I
      PEP-PCR. The modified I-PEP-PCR protocol was superior to the original PEP-PCR and
      DOP-PCR protocols concerning amplification of DNA from one cell (efficiency rate
      I-PEP-PCR 40% versus PEP-PCR 15% and DOP-PCR 30%) and five cells (efficiency rate
      I-PEP-PCR 100% versus PEP-PCR 33% and DOP-PCR 20%). Preamplification by I-PEP
      allowed 100% sequence accuracy in > 4000 sequenced base pairs and Ki-ras mutation
      detection in isolated single disseminated tumor cells. For reliable
      microsatellite analysis of I-PEP-preamplified DNA, at least 10 unfixed cells from
      fluorescence-activated cell sorting, 10 cells from frozen tissue, or at least 30
      cells from formalin-fixed and paraffin-embedded tissue sections were required.
      Thus, I-PEP-PCR allowed multiple reliable microsatellite analyses suited for
      microsatellite instability and losses of heterozygosity and mutation analysis
      even at the single cell level, rendering this technique a powerful new tool for
      molecular analyses in diagnostic and experimental tumor pathology.

PMID- 9916923
TI  - Rapid simultaneous amplification and detection of the MBR/JH chromosomal
      translocation by fluorescence melting curve analysis.
AB  - Polymerase chain reaction (PCR) amplification and product analysis for the
      detection of chromosomal translocations, such as the t(14;18), has traditionally
      been a two-step process. PCR product detection has generally entailed gel
      electrophoresis and/or hybridization or sequencing for confirmation of assay
      specificity. Using a microvolume fluorimeter integrated with a thermal cycler and
      a PCR-compatible double-stranded DNA (dsDNA) binding fluorescent dye (SYBR Green
      I), we investigated the feasibility of simultaneous thermal amplification and
      detection of MBR/JH translocation products by fluorescence melting curve
      analysis. We analyzed DNA from 30 cases of lymphoproliferative disorders
      comprising 19 cases of previously documented MBR/JH-positive follicle center
      lymphoma and 11 reactive lymphadenopathies. The samples were coded and analyzed
      blindly for the presence of MBR/JH translocations by fluorescence melting curve
      analysis. We also performed dilutional assays using the MBR/JH-positive cell line
      SUDHL-6. Multiplex PCR for MBR/JH and beta-globin was used to simultaneously
      assess sample adequacy. All (100%) of the 19 cases previously determined to be
      MBR/JH positive by conventional PCR analysis showed a characteristic sharp
      decrease in fluorescence at approximately 90 degrees C by melting curve analysis
      after amplification. Fluorescence melting peaks obtained by plotting the negative
      derivative of fluorescence over temperature (-dF/dT) versus temperature (T)
      showed melting temperatures (Tm) at 88.85+/-1.15 degrees C. In addition,
      multiplex assays using both MBR/JH and beta-globin primers yielded easily
      distinguishable fluorescence melting peaks at approximately 90 degrees C and 81.2
      degrees C, respectively. Dilutional assays revealed that fluorescence melting
      curve analysis was more sensitive than conventional PCR and agarose gel
      electrophoresis with ultraviolet transillumination by as much as 100-fold.
      Simultaneous amplification and fluorescence melting curve analysis is a simple,
      reliable, and sensitive method for the detection of MBR/JH translocations. The
      feasibility of specific PCR product detection without electrophoresis or
      utilization of expensive fluorescently labeled probes makes this method
      attractive for routine molecular diagnostics.

PMID- 9916924
TI  - Active transforming growth factor-beta in wound repair: determination using a new
      assay.
AB  - Transforming growth factor (TGF)-beta regulates wound repair and scarring in an
      isoform-specific fashion. TGF-beta is produced in a latent form, and its
      activation is a critical regulatory step controlling the bioactivity of this
      growth factor. To date, it has been impossible to determine latent TGF-beta
      activation in vivo due to a lack of quantitative assays. We describe here a
      semiquantitative modification of the plasminogen activator inhibitor-1/luciferase
      bioassay (PAI/L assay) for TGF-beta, which we used to determine active and latent
      TGF-beta isoforms in frozen sections of rat wound tissue. We found that
      significant amounts of latent TGF-beta were rapidly activated upon wounding (38%
      of the total TGF-beta at 1 hour after wounding). A second peak of active TGF-beta
      (17% of total) occurred at 5 days after wounding. The predominant isoforms were
      TGF-beta1 and -2 with only minor amounts of TGF-beta3 present. This is the first
      TGF-beta bioassay allowing semiquantitative determination of active and latent
      isoforms present in vivo, and our results document the significance and temporal
      regulation of latent TGF-beta isoform activation in wound repair.

PMID- 9916925
TI  - Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is
      associated with high tumor cell proliferation.
AB  - Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14,
      has been found as an alternative genetic alteration to CDKN2A inactivation in
      various human tumors including malignant gliomas and sarcomas. In the present
      study, we have evaluated the frequency of the CDK4 gene amplification in sporadic
      breast cancer by applying a nonradioactive quantitative differential polymerase
      chain reaction based on fluorescent DNA technology. Fluorescent-labeled
      polymerase chain reaction products were analyzed with an automated DNA sequencer.
      Amplification of CDK4 gene was detected in 15 (15.8%) of 95 breast cancers. All
      tumors with CDK4 gene amplification showed high CDK4 protein expression
      determined by immunohistochemistry. Furthermore, the mean Ki-67 labeling index in
      tumors with CDK4 gene amplification was significantly higher than in those
      without CDK4 gene amplification. No significant associations were observed
      between CDK4 gene amplification and any specific histopathological parameter. The
      findings of this study provide the first evidence of CDK4 gene amplification in
      breast cancer and suggest that CDK4 gene amplification appears to be of
      importance in the pathogenesis of a subset of sporadic breast cancer.

PMID- 9916926
TI  - Expression of the cell cycle inhibitor p27KIP1 is a new prognostic marker
      associated with survival in epithelial ovarian tumors.
AB  - This case-control study was designed to identify factors associated with long
      term survival. We examined two groups of patients with epithelial ovarian cancer,
      one group of long-term survivors (> 5 years) and one group of short-term
      survivors (< 2 years), for levels of expression of p53 and p27KIP1 proteins (as
      both proteins have been shown to be independent prognostic markers in tumors
      other than ovary) and the relationship with patient survival. Our findings show
      that p27KIP1 expression, in contrast to p53 expression, is positively associated
      with long-term survival in univariate analysis (P = 0.001), in analyses
      stratified by residual disease (P = 0.02) or performance status (P = 0.02), the
      two strongest prognostic factors for ovarian cancer, as well as multivariate
      analysis (P = 0.002) adjusting simultaneously for age, tumor stage, residual
      disease, performance status, and grade of differentiation. Therefore,
      immunostaining for levels of p27KIP1 expression may have potential as a new
      prognostic factor in the management of ovarian cancer.

PMID- 9916927
TI  - Familial adenomatous polyposis-associated thyroid cancer: a clinical,
      pathological, and molecular genetics study.
AB  - We report two familial adenomatous polyposis (FAP) kindreds with thyroid cancer,
      harboring two apparently novel germlineAPC mutations. The clinical phenotype in
      the first kindred was typical of classical adenomatous polyposis, whereas the
      second kindred exhibited an attenuated adenomatous polyposis phenotype. There was
      a female predominance with a mean age of 34 years (range, 23-49) at cancer
      diagnosis. Multiple sections of four thyroid tumors from three FAP patients were
      analyzed in detail. Histological examination of thyroid tumors showed a range of
      morphological features. Some tumors exhibited typical papillary architecture and
      were associated with multifocal carcinoma; in others, there were unusual areas of
      cribriform morphology, and spindle-cell components with whorled architecture.
      Immunoreactivity for thyroglobulin and high molecular weight keratins was strong.
      Somatic APC mutation analysis revealed an insertion of a novel long interspersed
      nuclear element-1-like sequence in one tumor sample, suggesting disruption of
      APC. In three FAP patients, ret/PTC-1 and ret/PTC-3 were expressed in thyroid
      cancers. No positivity was observed for ret/ PTC-2. p53 immunohistochemistry was
      positive in only one section of a recurrent thyroid tumor sample. Our data
      suggest that genetic alterations in FAP-associated thyroid cancer involve loss of
      function of APC along with the gain of function of ret/PTC, while alterations of
      p53 do not appear to be an early event in thyroid tumorigenesis.

PMID- 9916928
TI  - Protein kinase C isoenzyme patterns characteristically modulated in early
      prostate cancer.
AB  - Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -epsilon, 
      gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common receptor for
      activated C-kinase (RACK)-1, was determined immunohistochemically using specific
      antibodies in formalin-fixed and paraffin-embedded specimens of early prostatic
      adenocarcinomas (n = 23) obtained at radical prostatectomy. Expression of each
      isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues
      removed at radical cystectomy (n = 10). The most significant findings were
      decreased PKC-beta expression in early neoplasia when compared to benign
      epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC
      epsilon (P < 0.0001). Detectable levels of PKC-alpha and PKC-zeta were also
      significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but
      did not correlate with either PKC-beta or PKC-epsilon for individual cases.
      Alterations in the levels of the four PKC isoenzymes occurred specifically and
      consistently during the genesis and progression of human prostate cancer. PKC
      delta, -gamma, and -theta were not expressed in the epithelium of either the
      benign prostates or the cancers. Levels of expression for PKC-A, -iota, -mu, and
      RACK-1 were not significantly different between the benign and malignant groups.
      Although changes in PKC isoenzyme expression may assist in explaining an altered
      balance between proliferation and apoptosis, it is likely that changes in
      activity or concentrations of these isoenzymes exert important modulating
      influences on particular pathways regulating cellular homeostasis. The findings
      of this study raise an exciting possibility of novel therapeutic intervention to
      regulate homeostatic mechanisms controlling proliferation and/or apoptosis,
      including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+
      concentrations, and enhanced cellular mobility resulting in the metastatic
      dissemination of human prostate cancer cells. Attenuation of PKC-beta expression
      is currently being assessed as a reliable objective adjunct to morphological
      appearance for the diagnosis of early progressive neoplasia in human prostatic
      tissues.

PMID- 9916929
TI  - Expression of inducible nitric oxide synthase in human granulomas and histiocytic
      reactions.
AB  - Inducible nitric oxide synthase (iNOS) is required in immune response against
      infections and is involved in granuloma formation in animals; in murine
      macrophages, iNOS is induced by lipopolysaccharide and interferon-gamma. In
      contrast, the role of iNOS in human immune response against infections is still
      questioned, and its expression in granulomas is poorly investigated. Using
      Western blotting and immunohistochemistry, we investigated iNOS expression in
      human lymph nodes with nonspecific reactions and in tissues containing granulomas
      caused by mycobacteria, Toxoplasma, Cryptococcus neoformans, Leishmania,
      Bartonella, noninfectious granulomas (sarcoidosis, foreign body), and other
      hystiocitic reactions (Kikuchi's disease, Omenn syndrome). iNOS was undetectable
      in nonspecific reactive lymphadenitis, foreign-body granulomas, and Omenn
      syndrome, whereas it was strongly expressed in infectious granulomas,
      sarcoidosis, and Kikuchi's diseases. Immunohistochemistry demonstrated that iNOS
      was selectively expressed by the epithelioid and multinucleated giant cells
      within the granulomas. Use of an anti-nitrotyrosine antibody, recognizing
      nitrosilated amino acid residues derived from nitric oxide production, revealed a
      consistent positivity within the cells expressing iNOS, thus suggesting that iNOS
      is functionally active. Detection of cytokines by reverse transcriptase
      polymerase chain reaction demonstrated that tissues that were positive for iNOS,
      also expressed the Thl-type cytokine interferon-gamma mRNA, but not the Th2-type
      cytokine interleukin-4. Taken together, these results indicate that iNOS is
      involved in different human immune reactions characterized by
      histiocytic/granulomatous inflammation and associated with Th1-type cytokine
      secretion.

PMID- 9916931
TI  - Novel approach to specific growth factor inhibition in vivo: antagonism of
      platelet-derived growth factor in glomerulonephritis by aptamers.
AB  - Mesangial cell proliferation and matrix accumulation, driven by platelet-derived
      growth factor (PDGF), contribute to many progressive renal diseases. In a novel
      approach to antagonize PDGF, we investigated the effects of a nuclease-resistant
      high-affinity oligonucleotide aptamer in vitro and in vivo. In cultured mesangial
      cells, the aptamer markedly suppressed PDGF-BB but not epidermal- or fibroblast
      growth-factor-2-induced proliferation. In vivo effects of the aptamer were
      evaluated in a rat mesangioproliferative glomerulonephritis model. Twice-daily
      intravenous (i.v.) injections from days 3 to 8 after disease induction of 2.2
      mg/kg PDGF-B aptamer, coupled to 40-kd polyethylene glycol (PEG), led to 1) a
      reduction of glomerular mitoses by 64% on day 6 and by 78% on day 9, 2) a
      reduction of proliferating mesangial cells by 95% on day 9, 3) markedly reduced
      glomerular expression of endogenous PDGF B-chain, 4) reduced glomerular
      monocyte/macrophage influx on day 6 after disease induction, and 5) a marked
      reduction of glomerular extracellular matrix overproduction (as assessed by
      analysis of fibronectin and type IV collagen) both on the protein and mRNA level.
      The administration of equivalent amounts of a PEG-coupled aptamer with a
      scrambled sequence or PEG alone had no beneficial effect on the natural course of
      the disease. These data show that specific inhibition of growth factors using
      custom-designed, high-affinity aptamers is feasible and effective.

PMID- 9916930
TI  - Expression and regulation of cell adhesion molecules by hepatic stellate cells
      (HSC) of rat liver: involvement of HSC in recruitment of inflammatory cells
      during hepatic tissue repair.
AB  - Hepatic stellate cells (HSC), a pericyte-like nonparenchymal liver cell
      population, are regarded as the principal matrix-synthesizing cells of fibrotic
      liver. They might also play a role during liver inflammation. The present study
      analyzed (i) expression of cell adhesion molecules (CAMs) mediating cell
      infiltration, like intercellular adhesion molecule-1 (I-CAM-1) and vascular cell
      adhesion molecule-1 (V-CAM-1), by HSC, (ii) CAM regulation in HSC by growth
      factors and inflammatory cytokines, and (iii) CAM expression in situ during liver
      inflammation, using immunochemistry and Northern blot analysis. I-CAM-1 and V-CAM
      1 expression was present in HSC in vitro and in cells located in the
      sinusoidal/perisinusoidal area of normal liver. Growth factors, eg, transforming
      growth factor-beta1, down-regulated I-CAM-1- and V-CAM-1-coding mRNAs and
      stimulated N-CAM expression of HSC. In contrast, inflammatory cytokines like
      tumor necrosis factor-alpha reduced N-CAM-coding mRNAs, whereas induction of I
      CAM-1- and V-CAM-1-specific transcripts increased several fold. In situ,
      messengers specific for I-CAM-1 and V-CAM-1 were induced 3 hours after CCl4
      treatment (thereby preceding mononuclear cell infiltration starting at 12 hours),
      were expressed at maximal levels 9-12 hours after CCl4 application, and decreased
      afterwards. I-CAM-1 and V-CAM-1 immunoreactivity increased in a linear fashion
      starting 3 hours after CCl4-induced liver injury, was detected in highest amounts
      at 24-48 hours characterized by maximal cell infiltration, and returned to
      baseline values at 96 hours. Interestingly, the induction/repression of CAM
      specific messengers paralleled the time kinetics of tumor necrosis factor-alpha
      transforming growth factor-beta1 expression in injured liver. HSC might be
      important during the onset of hepatic tissue injury as proinflammatory elements
      and might interact with I-CAM-1 and V-CAM-1 ligand-bearing cells, namely
      lymphocyte function-associated antigen-1- or Mac-1/very late activation antigen-4
      positive inflammatory cells, thereby modulating the recruitment and migration of
      mononuclear cells within the perisinusoidal space of diseased livers.

PMID- 9916932
TI  - WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse
      mesangial sclerosis.
AB  - Denys-Drash syndrome is a rare disorder of urogenital development characterized
      by the association of early onset glomerulopathy caused by diffuse mesangial
      sclerosis, gonadal dysgenesis leading to pseudohermaphroditism in males, and a
      high risk of developing Wilms' tumor. The syndrome is caused by dominant negative
      point mutations in the WT1 gene that encodes a tumor suppressor transcription
      factor normally expressed in podocytes. Mutations usually affect the zinc fingers
      of the WT1 protein. The basic defect is unknown in most cases of isolated diffuse
      mesangial sclerosis, a disease characterized by the same glomerular changes as in
      Denys-Drash syndrome but possibly transmitted as an autosomal recessive trait.
      Here we show that the distribution of WT1 is abnormal in most patients with Denys
      Drash syndrome : WT1 nuclear staining of podocytes is decreased or absent. This
      finding is consistent with the decreased DNA binding capacity of the mutated
      protein. One target gene of WT1 is PAX2, the expression of which is down
      regulated in podocytes during early stages of nephrogenesis. We demonstrate that
      WT1 mislocalization is associated with abnormal podocyte expression of PAX2
      protein and RNA. We suggest that persistent expression of PAX2 is likely to
      result from the loss of WT1 dependent transcriptional repression and may
      participate in the pathological mechanisms leading to glomerular dysfunction.
      Abnormal distribution of WT1 and PAX2 was also observed in isolated diffuse
      mesangial sclerosis suggesting that a defect in WT1 could also be operative in
      isolated diffuse mesangial sclerosis. Primary involvement of PAX2 is an
      alternative hypothesis because persistent expression of PAX2 in transgenic mice
      is associated with the occurrence of early and severe glomerulopathy.

PMID- 9916933
TI  - CD95 ligand (CD95L) in normal human lymphoid tissues: a subset of plasma cells
      are prominent producers of CD95L.
AB  - CD95(Fas/APO-1)-ligand (CD95L) mediates apoptosis by trimerization of the CD95
      receptor on the surface of sensitive cells. In vitro studies have shown CD95L
      expression mainly by activated T cells and suggested a role for CD95L in the
      regulation of immune responses. Little is known, however, about the cellular
      distribution of CD95L in situ in the normal human immune system. We investigated
      CD95L expression in tissue sections of the thymus, lymph node, spleen, tonsil,
      and gastrointestinal tract using in situ hybridization and two monoclonal
      antibodies. In all these organs, cells expressing CD95L message and protein were
      scarce and comprised scattered lymphocytes, rare nonlymphoid cells, and a subset
      of epithelioid endothelial cells. Surprisingly, a subset of plasma cells turned
      out to be the most prominent producers of CD95L, matching the reports on CD95L in
      myeloma cells. CD95L+ plasma cells were most numerous in the mucosa-associated
      lymphoid tissue. This also applied to acquired mucosa-associated lymphoid tissue
      in chronic gastritis in which CD95L+ plasma cells were found scattered in the
      lamina propria. Our data suggest that plasma cells as yet may be neglected
      modulators of immune responses.

PMID- 9916934
TI  - Tumor necrosis factor-alpha mediates orthopedic implant osteolysis.
AB  - Osteolysis complicating arthroplasty reflects progressive generation of implant
      derived wear particles, which prompt an inflammatory reaction attended by
      recruitment of osteoclasts to the prosthesis-bone interface. To identify a
      soluble mediator of periprosthetic osteolysis we first showed that implant
      particles induce c-src in murine bone marrow macrophages (BMMs), a protein
      specifically expressed when these cells commit to the osteoclast phenotype. The
      fact that tumor necrosis factor-alpha (TNF) is a potent osteoclastogenic agent
      while at the same time is the only soluble moiety known to be c-src inductive
      suggests that this cytokine may mediate implant particle-induced
      osteoclastogenesis. Consistent with this hypothesis, prosthesis-derived wear
      particles, recovered at revision arthroplasty, dose-dependently prompt TNF
      secretion by BMMs. Similarly, particulate polymemthylmethacrylate, the major
      component of orthopedic implant cement, induces BMM expression of TNF mRNA and
      protein in a time- and dose-dependent manner. Furthermore, failure of BMMs
      derived from mice deleted of both the p55 and p75 TNF receptors to express c-src
      in response to polymemthyl-methacrylate indicates TNF is an essential mediator of
      particle induction of this osteoclast specific protein. To test the hypothesis
      that TNF mediates implant osteolysis, we established an in vivo murine model of
      this condition that histologically mirrors that of man. Verifying that TNF is
      essential to development of particle osteolysis, mice failing to express both the
      p55 and p75 TNF receptors are protected from the profound bone resorption
      attending polymemthyl-methacrylate particle implantation on calvariae of wild
      type animals. Finally, the protective effect of deletion of both TNF receptors is
      recapitulated in mice lacking only the p55 receptor. Thus, targeting TNF and/or
      its p55 receptor may arrest wear particle osteolysis.

PMID- 9916935
TI  - In situ detection of tissue factor within the coronary intima in rat cardiac
      allograft vasculopathy.
AB  - Cardiac allograft vasculopathy is a major cause of morbidity and mortality of
      cardiac transplant recipients. The underlying cause of this disease remains
      unclear. Histological studies have implicated accelerated hemostasis and
      intravascular fibrin deposition in its pathogenesis. In the present study a
      defined model of this disease in the rat was used to elucidate the implication of
      tissue factor in the production of the hypercoagulable state observed in cardiac
      allograft vessels. Tissue factor protein and mRNA expression were studied in rat
      heart allografts developing allograft vasculopathy resembling human disease.
      Immunohistochemistry demonstrated tissue-factor-positive cells present in the
      allograft coronary intima and adventitia. Significant staining for tissue factor
      was detected in the endothelium lining coronary lesions in cardiac allografts and
      in interstitial mononuclear cells, respectively. Both transplant coronary
      endothelial cells and mononuclear cells contained tissue factor mRNA as indicated
      by oligo-cell reverse transcription polymerase chain reaction after laser
      assisted cell picking. In contrast, tissue factor mRNA and protein were not or
      negligibly detectable within the coronary intima of nontransplanted control
      hearts. Thus, the present study clearly demonstrates that aberrant tissue factor
      expression occurs within the coronary intima after cardiac transplantation.
      Tissue factor, activating downstream coagulation mechanisms, may account for the
      intravascular clotting abnormalities observed in cardiac allografts and may
      represent a key factor in transplant atherogenesis.

PMID- 9916936
TI  - Hereditary amyloid cardiomyopathy caused by a variant apolipoprotein A1.
AB  - Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac
      presentation and death from heart failure by the sixth or seventh decade was
      found to be associated with a previously unreported point mutation (thymine to
      cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene. The predicted
      substitution of proline for leucine at amino acid position 90 was confirmed by
      structural analysis of amyloid protein isolated from cardiac deposits of amyloid.
      The subunit protein is composed exclusively of NH2-terminal fragments of the
      variant apoA1 with the longest ending at residue 94 in the wild-type sequence.
      Amyloid fibrils derived from four previously described apoA1 variants are
      composed of similar fragments with carboxyl-terminal heterogeneity, but contrary
      to those variants, which all carry one extra positive charge, the substitution
      Leu90Pro does not result in any charge modification. It is unlikely, therefore,
      that amyloid fibril formation is related to change of charge for a specific
      residue of the precursor protein. This is in agreement with studies on
      transthyretin amyloidosis in which no unifying factor such as change of charge
      for amino acid residues has been noted.

PMID- 9916937
TI  - T lymphocytes induce endothelial cell matrix metalloproteinase expression by a
      CD40L-dependent mechanism: implications for tubule formation.
AB  - Neovascularization frequently accompanies chronic immune responses characterized
      by T cell infiltration and activation. Angiogenesis requires endothelial cells
      (ECs) to penetrate extracellular matrix, a process that involves matrix
      metalloproteinases (MMPs). We report here that activated human T cells mediate
      contact-dependent expression of MMPs in ECs through CD40/CD40 ligand signaling.
      Ligation of CD40 on ECs induced de novo expression of gelatinase B (MMP-9),
      increased interstitial collagenase (MMP-1) and stromelysin (MMP-3), and activated
      gelatinase A (MMP-2). Recombinant human CD40L induced expression of MMPs by human
      vascular ECs to a greater extent than did maximally effective concentrations of
      interleukin-1beta or tumor necrosis factor-alpha. Moreover, activation of human
      vascular ECs through CD40 induced tube formation in a three-dimensional fibrin
      matrix gel assay, an effect antagonized by a MMP inhibitor. These results
      demonstrated that activation of ECs by interaction with T cells induced synthesis
      and release of MMPs and promoted an angiogenic function of ECs via CD40L-CD40
      signaling. As vascular cells at the sites of chronic inflammation, such as
      atherosclerotic plaques, express CD40 and its ligand, our findings suggest that
      ligation of CD40 on ECs can mediate aspects of vascular remodeling and neovessel
      formation during atherogenesis and other chronic immune reactions.

PMID- 9916938
TI  - Inhibition of NF-kappaB activation and augmentation of IkappaBbeta by secretory
      leukocyte protease inhibitor during lung inflammation.
AB  - In earlier experiments, exogenous administration of secretory leukocyte protease
      inhibitor (SLPI) suppressed acute lung injury induced by deposition of IgG immune
      complexes. In the current studies we examined the mechanism of the protective
      effects of SLPI in this model. The presence of SLPI in the IgG immune complex
      model of lung injury reduced the increase in extravascular leakage of 125I
      albumin, the intensity of up-regulation of lung vascular intercellular adhesion
      molecule-1, and the numbers of neutrophils accumulating in the lung. The presence
      of SLPI caused greatly reduced activation (ie, nuclear translocation) of the
      transcription nuclear factor-kappaB (NF-kappaB) in lung cells but did not
      suppress activation of lung mitogen-activated protein kinase. SLPI did not alter
      NF-kappaB activation in alveolar macrophages harvested 30 minutes after
      initiation of lung inflammation. In the presence of SLPI, content of tumor
      necrosis factor-alpha, CXC chemokines, and C5a in bronchoalveolar fluids was
      unaffected. In the inflamed lungs, inhibition of NF-kappaB activation by SLPI was
      associated with elevated levels of lung IkappaBbeta (but not IkappaBalpha)
      protein in the absence of elevated mRNA for IkappaBbeta. When instilled into
      normal lung, SLPI also caused similar changes (increases) in lung IkappaBbeta.
      Finally, in the lung inflammatory model used, the presence of anti-SLPI caused
      accentuated activation of NF-kappaB. These data confirm the anti-inflammatory
      effect of SLPI in lung and point to a mechanism of anti-inflammatory effects of
      SLPI. SLPI appears to function as an endogenous regulator of lung inflammation.

PMID- 9916939
TI  - Monoclonality of atypical adenomatous hyperplasia of the lung.
AB  - Atypical adenomatous hyperplasia (AAH) of the lung has been postulated as a
      possible precursor lesion of bronchioloalveolar carcinoma (BAC). The clonality of
      AAHs from seven female patients was analyzed to determine whether AAH is a
      monoclonal expansion. All AAHs were identified in lungs surgically resected for
      BAC. The clonality of the BAC and bronchiolar metaplasia in each case was also
      analyzed. Approximately 500 cells in each lesion were precisely microdissected
      from methanol-fixed sections. Adjacent normal lung tissue was collected as a
      normal control. DNA was extracted for clonal analysis based on an X-chromosome
      linked polymorphic marker, the human androgen receptor gene (HUMARA). HUMARA was
      found to be amplified with or without previous digestion by the methylation
      sensitive restriction endonuclease Hpa II. Five cases were informative. All 10
      AAHs and 7 BACs obtained from the informative cases showed monoclonality, whereas
      the control cells showed polyclonality. Three different AAH lesions in a single
      case showed both possible patterns of monoclonality. BAC and contiguous AAH
      showed identical monoclonality in two cases. Two lesions of bronchiolar
      metaplasia, which was considered reactive, were polyclonal. Our results
      demonstrated the monoclonal nature of AAH, and this finding suggests that AAH is
      a precursor of BAC or a preneoplastic condition.

PMID- 9916942
TI  - Regulation of the spatial organization of mesenchymal connective tissue: effects
      of cell-associated versus released isoforms of platelet-derived growth factor.
AB  - Platelet-derived growth factor (PDGF), a mitogen and chemoattractant for
      mesenchymal cells, occurs as cell-associated or released isoforms. To investigate
      their in vivo role, human keratinocytes, which normally synthesize both types of
      PDGF, were genetically modified to overexpress either wild-type PDGF-B (cell
      associated) or the truncation mutant PDGF-B211 (released). Cells expressing the
      mutant isoform released 20 times more PDGF (145 ng/hour/10(7) cells) than cells
      expressing the wild-type isoform (6 ng/ hour/10(7) cells). When grafted as
      epithelial sheets onto athymic mice, modified cells formed a stratified
      epithelium and induced a connective tissue response that differed depending on
      the PDGF isoform expressed. Expression of PDGF-B211 induced a thick connective
      tissue with increased numbers of fibroblasts, mononuclear cells, and blood
      vessels evenly distributed throughout the connective tissue layer, whereas
      expression of PDGF-B induced a zone of fibroblasts and mononuclear cells
      localized to the interface of the epidermis and connective tissue, which often
      disrupted the continuity of the basement membrane. Immunostaining revealed that
      wild-type PDGF protein was deposited in the basement membrane region. These data
      suggest that the different binding properties of PDGF isoforms control the
      spatial organization of cellular events in regenerating mesenchymal tissue in
      vivo.

PMID- 9916941
TI  - Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in
      the cortex during aging.
AB  - We previously noted that some aged human cortical specimens containing very low
      or negligible levels of amyloid beta-protein (As) by enzyme immunoassay (EIA)
      provided prominent signals at 6 approximately 8 kd on the Western blot, probably
      representing sodium dodecyl sulfate (SDS)-stable Abeta dimer. Re-examination of
      the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most
      commonly used for the quantitation of Abeta, capture SDS-dissociable Abeta but
      not SDS-stable Abeta dimer. Thus, all cortical specimens in which the levels of
      Abeta were below the detection limits of EIA were subjected to Western blot
      analysis. A fraction of such specimens contained SDS-stable dimer at 6
      approximately 8 kd, but not SDS-dissociable A(beta) monomer at approximately 4
      kd, as judged from the blot. This A(beta) dimer is unlikely to be generated after
      death, because (i) specimens with very short postmortem delay contained the
      A(beta) dimer, and (ii) until 12 hours postmortem, such SDS-stable A(beta) dimer
      is detected only faintly in PDAPP transgenic mice. The presence of A(beta) dimer
      in the cortex may characterize the accumulation of A(beta) in the human brain,
      which takes much longer than that in PDAPP transgenic mice.

PMID- 9916940
TI  - Transgenic expression of the shortest human tau affects its compartmentalization
      and its phosphorylation as in the pretangle stage of Alzheimer's disease.
AB  - We have generated transgenic mice expressing the shortest human tau protein, the
      microtubule-associated protein that composes paired helical filaments in
      Alzheimer's disease. Transgenic tau transcripts and proteins were strongly
      expressed in neurons in the developing and adult brain. In contrast to the
      endogenous tau that progressively disappeared from neuronal cell bodies during
      development, the human transgenic tau remained abundant in cell bodies and
      dendrites of a subset of neurons in the adult. This somatodendritic transgenic
      tau was immunoreactive with antibodies to tau phosphorylated on Thr181 and Thr231
      and with the conformation-dependent Alz50 antibody. A few astrocytes expressing
      the transgenic tau were strongly immunoreactive with antibodies to additional tau
      phosphorylation sites, ie, at Ser262/ 356 and Ser396/404. All of these
      phosphorylation sites have been identified in paired helical filaments-tau
      proteins. In electron microscopy, the transgenic tau was detected into
      microtubules in axons and in dendrites but not in cell bodies. Neurofibrillary
      tangles were not detected in transgenic animals examined up to the age of 19
      months. These results indicate that transgenic manipulation of tau expression and
      intracellular targeting is sufficient per se to affect tau compartmentalization,
      phosphorylation, and conformation partly as it is observed at the pretangle stage
      in Alzheimer's disease.

PMID- 9916943
TI  - Structural variability of CD44v molecules and reliability of immunodetection of
      CD44 isoforms using mAbs specific for CD44 variant exon products.
AB  - CD44 can be considered structurally and functionally one of the most variable
      surface molecules. Alternative splicing of variant exons as well as
      posttranslational modifications of the molecule (differences in glycosylation)
      generate a rich repertoire of CD44 isoforms (CD44v), some of which seem to play a
      key role in tumor growth and progression. Immunodetection of CD44 isoforms in
      vivo, using mAbs specific for CD44 variant exon products, is largely used to
      identify those CD44 molecules involved in tumor growth and progression and to
      interfere with CD44-mediated processes. In the present work we demonstrate that
      the immunoreactivity of some mAbs directed to CD44 exon-specific epitopes can be
      impaired by the structural variability of the molecule. Our findings demonstrate
      that (1) specific exon assortment and/or posttranslational modifications of CD44v
      molecules can mask CD44 exon-specific epitopes; (2) glycosaminoglycan side
      chains, carried by some CD44v isoforms of high molecular weight, may play a
      critical role in determining the exact conformation of the molecule, which is
      necessary for the detection of CD44 variant epitopes by specific mAbs; and (3) in
      a panel of stable transfectants expressing CD44 N-glycosylation site-specific
      mutants, generated in the constant region of CD44 extracellular domain,
      asparagine-isoleucine substitution is sufficient per se to impair the
      immunoreactivity of several mAbs to pan-CD44. Thus, conformational changes due to
      the alternative splicing of CD44 variant exons and/or posttranslational
      modifications of the molecule (different degree of glycosylation), which are cell
      type-specific, are likely to generate CD44 variants that elude immunodetection.
      These findings strongly suggest that immunohistochemical analysis of CD44
      expression in vitro and in vivo, using mAbs specific for CD44 variant exon
      epitopes, can potentially be impaired by a large number of false negative
      results.

PMID- 9916945
TI  - Obstetrics and gynecology: a unique surgical specialty.

PMID- 9916944
TI  - Transforming growth factor-beta1 fails to stimulate wound healing and impairs its
      signal transduction in an aged ischemic ulcer model: importance of oxygen and
      age.
AB  - Clinical trials of exogenous growth factors in treating chronic wounds have been
      less successful than expected. One possible explanation is that most studies used
      animal models of acute wounds in young animals, whereas most chronic wounds occur
      in elderly patients with tissue ischemia. We described an animal model of age-
      and ischemia-impaired wound healing and analyzed the wound-healing response as
      well as the transforming growth factor (TGF)-beta1 effect in this model. Rabbits
      of increasing ages were made ischemic in the ear where dermal ulcers were
      created. Histological analysis showed that epithelium ingrowth and granulation
      tissue deposition were significantly impaired with increased age under ischemia.
      TGF-beta1 stimulated wound repair under both ischemic and non-ischemic conditions
      in young animals, although it showed no statistical difference in aged animals.
      Procollagen mRNA expression decreased under ischemic conditions and with aging.
      Neither TGF-beta1 nor procollagen alpha1(I) mRNA expression increased in response
      to TGF-beta1 treatment under ischemia in aged animals. Therefore, the wound
      healing process is impaired additively by aging and ischemia. The lack of a wound
      healing response to TGF-beta1 in aged ischemic wounds may play a role in the
      chronic wounds.

PMID- 9916946
TI  - Efficacy of treatment for syphilis in pregnancy.
AB  - OBJECTIVE: To evaluate prospectively the Centers for Disease Control and
      Prevention (CDC) recommended regimens for the treatment of antepartum syphilis
      and prevention of congenital syphilis. METHODS: This was a prospective evaluation
      of recommended syphilis treatment regimens from September 1, 1987, to August 31,
      1989, at Parkland Memorial Hospital, Dallas, Texas. Women with syphilis were
      staged and treated according to CDC recommendations. Treatment included 2.4
      million units of intramuscular (IM) benzathine penicillin G for primary,
      secondary, or early latent (less than 1 year) syphilis. Women with late latent
      (uncertain or longer than 1 year) syphilis were treated with 7.2 million units of
      benzathine penicillin G IM over 3 weeks. RESULTS: During the study period, 448 of
      28,552 women (1.6%) delivered were diagnosed with syphilis. One hundred eight
      were diagnosed at delivery and treated postpartum. The remaining 340 (75.9%)
      gravidas with untreated syphilis attending prenatal clinic comprised the study
      group. The success of therapy in preventing congenital syphilis was as follows:
      primary syphilis, 27 of 27; secondary syphilis, 71 of 75; early latent syphilis,
      100 of 102; and late latent syphilis, 136 of 136. The success rate for all stages
      of syphilis was 334 of 340 (98.2%). The success rate of therapy in secondary
      syphilis was significantly different from that of the other groups (P = .03). Two
      of the six fetal treatment failures produced preterm stillborns. Only one
      maternal treatment failure occurred, in a human immunodeficiency virus-infected
      woman. CONCLUSION: The CDC-recommended regimens for the prevention of congenital
      syphilis and treatment of maternal infection are effective, but the highest risk
      of fetal treatment failure exists with maternal secondary syphilis.

PMID- 9916947
TI  - Childbearing beyond age 40: pregnancy outcome in 24,032 cases.
AB  - OBJECTIVE: To examine pregnancy outcomes in women age 40 or older. METHODS: We
      used data from the California Health Information for Policy Project, which
      consists of linked records from the birth certificate and the hospital discharge
      record of both mother and newborn of all births that occurred in acute care
      civilian hospitals in California between January 1, 1992, and December 31, 1993.
      The study population consisted of all women who delivered at age 40 or over. The
      control population was women who delivered between age 20 and 29 years during
      this 2-year period. We reviewed gestational age at delivery, birth weight, mode
      and type of delivery, discharge summary and birth certificate demographics, birth
      outcome, pregnancy, and delivery data. RESULTS: Approximately 1,160,000 women
      delivered during the study period, and 24,032 (2%) of these women were age 40 or
      older. Of this latter group, 4777 (20%) were nulliparous. The cesarean delivery
      rate for nulliparous women in the study population was 47.0%, and the rate for
      multiparous patients in this group was 29.6%. The cesarean delivery rate was
      22.5% for nulliparous and 17.8% for multiparous women in the control group. In
      the older group, the operative vaginal delivery rate (forceps and vacuum) was
      14.2% for nulliparous women and 6.3% for multiparous women. Rates of birth
      asphyxia, fetal growth restriction, malpresentation, and gestational diabetes
      were significantly higher among older nulliparas (6, 2.5, 11, and 7%,
      respectively) compared with rates among control nulliparas (4, 1.4, 6, and 1.7%,
      respectively), and there were similar significant increases among older
      multiparas (3.4, 1.4, 6.9, and 7.8%, respectively), compared with younger
      multiparous controls (2.4, 1, 3.7, and 1.6%, respectively). Mean (+/- standard
      error) birth weight of infants delivered by older nulliparous women was 3201+/-10
      g, significantly lower than that among nulliparous controls (3317+/-1 g), whereas
      mean birth weight in the group of older multiparas (3381+/-5 g) was no different
      than that among younger multiparous controls (3387+/-1 g). Gestational age at
      delivery was significantly lower among older nulliparas (273.4+/-0.4 days),
      compared with nulliparous controls (278.5+/-0.05 days), and similarly lower among
      older multiparous women (274.0+/-0.2 days), compared with multiparous controls
      (278.3+/-0.05 days). More white women age 40 or over than younger white women
      were having a first child (64 and 39%, respectively). CONCLUSION: Nulliparous
      women age 40 or over have a higher risk of operative delivery (cesarean, forceps,
      and vacuum deliveries: 61%) than do younger nulliparous women (35%). This
      increase occurs in spite of lower birth weight and gestational age and may be
      explained largely by the increase in other complications of pregnancy. The
      increased frequency at which white women are having their first child at age 40
      or over may reflect career choices that involve delaying childbirth until the
      fifth decade of life. These data will allow us better to counsel patients about
      their pregnancy expectations and possible outcomes.

PMID- 9916948
TI  - Thyroid function in mothers of hypothyroid newborns.
AB  - OBJECTIVE: To assess etiologic significance of maternal autoimmune thyroid
      disease on incidence of transient congenital hypothyroidism in newborns. METHODS:
      Thyroid function was assessed in 259 mothers of hypothyroid newborns from the
      Quebec newborn screening program between 1984 and 1996. Maternal blood samples
      were taken routinely at the time of follow-up serum sampling of the infants, for
      measurements of free thyroxine, TSH, and antimicrosomal autoantibodies. Thyroid
      scans were conducted to characterize the type of thyroid dysfunction in affected
      infants. Results were compared with similar data from a control population of
      1773 pregnant women recruited from Quebec City between 1991 and 1992. These
      samples were collected at routine second-trimester prenatal screenings. RESULTS:
      The mothers of congenitally hypothyroid infants had higher prevalence of
      suppressed serum TSH concentrations compared with the control population (6.1%
      versus 2.9%, P = .01), higher prevalence of increased serum TSH levels (7.0%
      versus 0.9%, P < .001), and similar prevalence of positive antimicrosomal
      antibodies (11.6% versus 12.1%, P = .90). The prevalence of transient congenital
      hypothyroidism in the study population of hypothyroid infants was 27%, which is
      significantly greater than the 15% observed in our overall population of 523
      congenitally hypothyroid infants studied between 1974 and 1996 (P = .04).
      Antimicrosomal antibodies were demonstrable in ten (77%) of 13 mothers of infants
      with transient congenital hypothyroidism, and antimicrosomal antibodies or
      abnormal serum TSH levels in 13 of 13 (100%). CONCLUSION: These results indicate
      that most, if not all, cases of transient congenital hypothyroidism were
      attributable to maternal autoimmune thyroid disease, and presumably to maternal
      TSH receptor-blocking antibody. They suggest that maternal autoimmune thyroid
      disease is associated with much higher prevalence of transient congenital
      hypothyroidism than suspected. Because of the 20% prevalence of autoimmune
      thyroid disease and thyroid dysfunction in the mothers of congenitally
      hypothyroid infants, we recommend thyroid assessment of such women, if this
      information is not available.

PMID- 9916949
TI  - Ten-year follow-up of ovarian cancer patients after second-look laparotomy with
      negative findings.
AB  - OBJECTIVE: To determine long-term survival and predictors of recurrence in
      patients with platinum-treated ovarian cancer who were followed for 10 years
      after second-look laparotomy with negative findings. METHODS: Records were
      reviewed of 91 consecutive patients with negative findings on second-look
      laparotomy after platinum-based chemotherapy between January 1978 and January
      1987. Statistical analysis used Kaplan-Meier survival curves, Cox proportional
      hazards, and multiple logistic regression. RESULTS: Mean age of patients was 57
      (range 30-79) years. Distribution by stage and grade was as follows: stage I,
      ten; II, 18; III, 57; IV, six; grade 1, 18; 2, 28; 3, 45. Forty-seven of 91 women
      had optimal initial cytoreduction. Recurrence-free survival rates for all
      subjects were 75% at 2 years, 55% at 5 years, and 52% at 10 years. For women with
      stage I disease, the recurrence-free survival rate was 90% at 2, 5, and 10 years.
      For women with stage II disease, recurrence-free survival rates were 78, 72, and
      66% at 2, 5, and 10 years, respectively. Patients with stage III or IV disease
      had recurrence-free survival rates of 72, 44, and 40% at 2, 5, and 10 years,
      respectively. Risk of recurrent disease was related to tumor stage (relative risk
      [RR] 2.02; 95% confidence interval [CI] 1.2, 3.3; P = .005), grade (RR 2.00; 95%
      CI 1.3, 3.2; P = .004), and presence of a residual tumor of more than 2 cm at the
      end of initial surgery (RR 3.19; 95% CI 1.2, 8.5; P = .02). CONCLUSION: Ovarian
      cancer patients face an appreciable risk of recurrence in the first 5 years after
      second-look laparotomy with negative findings after platinum-based chemotherapy,
      but those who remain disease free at 5 years have excellent long-term survival
      rates. Tumor stage, grade, and presence of a residual tumor of more than 2 cm
      after initial surgery are significant predictors of recurrence.

PMID- 9916950
TI  - Maternal tobacco exposure and cotinine levels in fetal fluids in the first half
      of pregnancy.
AB  - OBJECTIVE: To evaluate the distribution of cotinine in fetal fluids and serum
      during the first half of pregnancy, and compare the fetal and maternal cotinine
      levels in passive and active smokers. METHODS: Maternal smoking status was
      determined by questionnaire in 85 pregnant women requesting abortion for
      psychosocial reasons between 7 and 17 weeks' gestation. Coelomic and amniotic
      fluid samples were collected between 7 and 11 weeks and fetal blood and amniotic
      fluid between 11 and 17 weeks. Cotinine levels were measured by radioimmunoassay.
      RESULTS: Women classified themselves as nonsmokers in 40 cases, passive smokers
      in 19 cases, and voluntary smokers in 26 cases. Five nonsmokers, 16 passive
      smokers, and all smokers had cotinine levels above the detection limit of the
      assay. Cotinine was invariably found in coelomic, amniotic, and fetal serum when
      maternal serum and urine cotinine levels exceeded 25 and 250 ng/mL, respectively.
      Higher cotinine levels were found in fetal fluids and serum than in maternal
      serum. Positive linear correlations were found between maternal urine and
      amniotic fluid cotinine concentrations (r = .75), between maternal urine cotinine
      concentration and number of cigarettes smoked per day (r = .66), and between
      maternal and fetal serum cotinine concentrations (r = .97). CONCLUSION: Cotinine
      accumulates in the fetal compartments as early as 7 weeks' gestation in both
      active and passive smokers. Women should be advised to give up smoking from
      conception and avoid environmental tobacco smoke exposure.

PMID- 9916951
TI  - Trends in United States ovarian cancer mortality, 1979-1995.
AB  - OBJECTIVE: To describe the epidemiology of ovarian cancer mortality in the United
      States from 1979 to 1995. METHODS: The mortality data of the Centers for Disease
      Control and Prevention were accessed using the Wide-ranging Online Data for
      Epidemiologic Research (WONDER). We selected all deaths among women with
      International Classification of Diseases, Ninth Revision (ICD-9) code 183.0
      (ovarian malignant neoplasm). Mortality data for the years 1979-1995 were age
      adjusted to the United States 1990 female population, and mortality rates for
      each year were calculated for females of all ages by age category, by race, and
      by geographic location. Trends were obtained for the periods 1979-1983 to 1991
      1995, and the impact on the number of ovarian cancer deaths was calculated.
      RESULTS: Age-adjusted ovarian cancer mortality rates have changed little in the
      United States from 1979 to 1995, but rates are increasing in older women (65
      years and older) and decreasing in younger women. Age-adjusted mortality rates
      are higher among whites than in blacks. Ovarian cancer mortality rates are higher
      in northern compared with southern states. CONCLUSION: The trends in ovarian
      cancer mortality among younger and older women parallel published changes in
      incidence and may be due to changes in risk factors, such as the use of oral
      contraceptives. The reasons for the higher ovarian cancer death rates in northern
      states are unknown. Better understanding of how modifiable risk factors and
      treatment methods affect ovarian cancer mortality trends is needed.

PMID- 9916953
TI  - A view from the family: years after a loved one has died of ovarian cancer.
AB  - OBJECTIVE: When cancer strikes a patient, it has a major impact on the family.
      Whereas many health care providers deal with the family while the patient is
      living, few have any long-term interactions after she has died. The purpose of
      this study is to interface with family members and reflect upon the impact
      ovarian cancer had on them. METHODS: A retrospective chart review was conducted
      of 222 patients who had been diagnosed and treated for ovarian carcinoma between
      the years 1990 and 1994 at Maine Medical Center, a tertiary care medical center.
      Of these, 34 patients who had been deceased for longer than 1 year were selected
      on the basis of specific criteria. The families of these individuals were each
      mailed a questionnaire comprising seven questions tailored to evaluate one family
      member's impressions and experiences of coping with a loved one who had died from
      ovarian cancer. Candid responses of any length were invited. RESULTS: Written
      responses were received from 32 of the 34 families that were mailed
      questionnaires. Of those responding, 65% were spouses, 22% were children, and 13%
      were siblings of the deceased. Each questionnaire was answered by only one
      relative, and the majority of questions posed received multiple detailed answers.
      According to the vast majority of respondents, the worst part of treatment was
      continuing chemotherapy. The most common emotion expressed by family members at
      the time of diagnosis was one of something having gone wrong. Both travel and
      living longer appeared to be the most treasured aspects of the patient's life
      once the diagnosis had been made. Watching their loved one suffer and the
      overwhelming sense of helplessness were the worst aspects of the disease process.
      The loved one was most often thought of on her birthday, and 90.6% of the
      respondents thought another female in their family was likely to get ovarian
      cancer. CONCLUSION: This study attempted to define those concerns and thoughts
      that remain important to family members whose loved ones had died from ovarian
      cancer. Common emotions expressed by family members years after the death of
      their loved one include their sense of surprise at the diagnosis, their sense of
      helplessness during the progression of the disease, and their pain in watching
      their loved one suffer. For them, the worst part of their loved one's treatment
      was continued chemotherapy, and a common unfounded fear was that another female
      family member would likely die from ovarian cancer. The responses encourage us as
      health care providers to remain in touch with these families even after the death
      of their loved one and to address the misconceptions, fears, and anxieties that
      our patients and their families may have.

PMID- 9916952
TI  - A population-based study of BRCA1 and BRCA2 mutations in Jewish women with
      epithelial ovarian cancer.
AB  - OBJECTIVE: To determine the frequency of BRCA1 mutations 185delAG and 5382insC
      and BRCA2 mutation 6174delT in Jewish women with ovarian cancer and in matched
      controls in a population-based study. METHODS: Forty-eight Jewish women with
      epithelial ovarian cancer (32 invasive and 16 borderline) and 33 Jewish control
      subjects were obtained from a population-based, case-control study of ovarian
      cancer in eastern Massachusetts and New Hampshire. Mutational analysis on exons 2
      and 20 of BRCA1 and exon 11 of BRCA2 was conducted on blood samples from patients
      and controls. RESULTS: Fourteen (44%) of 32 Jewish patients with invasive
      epithelial ovarian cancer carried either a 185delAG mutation of BRCA1 (n = 8) or
      a 6174delT mutation on BRCA2 (n = 6). Neither of these mutations was identified
      in 16 women with borderline ovarian tumors or in 33 controls. No 5382insC
      mutation of BRCA1 was identified in any of the patients or control subjects in
      the series. Family history did not predict mutation status. CONCLUSION: BRCA1
      185delAG and BRCA2 6174delT mutations are frequent in Jewish women with invasive
      epithelial ovarian cancer, irrespective of family history. Genetic counseling
      might be warranted in women with invasive epithelial ovarian cancer based on
      Jewish ethnicity alone.

PMID- 9916954
TI  - Early feeding compared with nasogastric decompression after major oncologic
      gynecologic surgery: a randomized study.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and tolerance of early feeding in
      patients undergoing surgery for gynecologic malignancies. METHODS: Patients were
      stratified according to operative time and type of tumor and were randomized into
      two arms: A) early oral feeding and B) nasogastric decompression followed by
      feeding at the first passage of flatus. Variables assessed included nausea,
      vomiting, time to first passage of flatus and stool, time elapsed before adequate
      tolerance of a regular diet, postoperative stay, and complications. RESULTS:
      Sixty-one patients were randomized into each arm. The types of tumor, the
      surgical procedures performed, and the operative times were similar in both
      groups. Early oral feeding in patients in arm A was associated with a
      significantly faster resolution of postoperative ileus (P < .01), with a more
      rapid return to a regular diet (P < .01), with an earlier first passage of stool
      (P < .01), and with a shorter postoperative stay (P < .05) than patients in arm
      B. Rates of nausea and vomiting were similar in both arms. Hindered deglutition
      and nasal soreness caused by the nasogastric tube were observed in 88% of
      patients in arm B. Insertion of a nasogastric tube was necessary in six patients
      in arm A (10%), and three of these had postoperative complications. Thus, early
      feeding was feasible in 95% of patients and did not seem to be related to
      preoperative chemotherapy, tumor type, or lymphadenectomy. CONCLUSION: Early
      feeding is feasible and well tolerated and is associated with reduced
      postoperative discomfort and a more rapid recovery in patients undergoing major
      surgery for gynecologic malignancies.

PMID- 9916955
TI  - Relationship between human papillomavirus type 16 in the cervix and
      intraepithelial neoplasia.
AB  - OBJECTIVE: To evaluate a temporal relationship between the presence of cervical
      human papilloma virus (HPV) type 16 and the risk of developing cervical
      intraepithelial neoplasia (CIN). METHODS: Fifty-four women with HPV 16 polymerase
      chain reaction (PCR)-positive tests were selected from the gynecologic outpatient
      clinic of the Reinier de Graaf Hospital, Delft, The Netherlands. At least three
      successive PCR tests were performed in each woman at intervals of 6 months. The
      PCR HPV 16 assay was performed in conjunction with cervical smear, and colposcopy
      and biopsy, if indicated. Women with at least three consecutive positive PCR
      tests were defined as having persistent HPV 16 infections. Women with one
      positive test followed by two negative tests were defined as having transient
      infections. Subdivided into two groups, 25 women had persistent infections and 29
      had transient infections. RESULTS: In significantly more women in the persistent
      group compared with the transient group, CIN developed (11 of 25 versus six of
      29, P = .036). Lesions in women with persistent HPV 16 infection were more severe
      (six of 11 were CIN III versus one of six P = .041). CONCLUSION: Persistent
      infection with HPV 16 is associated with a higher risk of developing CIN, which
      is often high-grade.

PMID- 9916956
TI  - Randomized controlled trial of depot leuprolide in patients with chronic pelvic
      pain and clinically suspected endometriosis. Pelvic Pain Study Group.
AB  - OBJECTIVE: To evaluate and compare the safety and efficacy of leuprolide versus
      placebo in managing chronic pelvic pain in women with clinically suspected
      endometriosis. METHODS: Women 18-45 years of age with moderate to severe pelvic
      pain of at least 6 months' duration underwent extensive, noninvasive diagnostic
      testing and laboratory evaluation, including pelvic ultrasound, complete blood
      count, determination of erythrocyte sedimentation rate, and endocervical
      cultures. Those with clinically suspected endometriosis were randomized to double
      blind treatment for 3 months with depot leuprolide (3.75 mg/mo) or placebo. The
      accuracy of the clinical diagnosis of endometriosis was evaluated by
      posttreatment laparoscopy. RESULTS: Of 100 women randomized, 95 completed the
      study: 49 in the leuprolide group and 46 in the placebo group. Women in the
      leuprolide group had clinically and statistically significant (P < or = .001)
      mean improvements from baseline after 12 weeks of therapy in all pain measures.
      These mean improvements were significantly greater (P < or = .001) than those in
      the placebo group. At 12 weeks, mean decreases in physician-rated scores for
      dysmenorrhea, pelvic pain, and pelvic tenderness were 1.7, 1.0, and 0.8 points
      greater, respectively, in the leuprolide group than in the placebo group (on a
      four-point scale). Thirty-eight (78%) of 49 and 40 (87%) of 46 patients in the
      leuprolide and placebo groups, respectively, had laparoscopically confirmed
      endometriosis after 12 weeks of treatment. No women withdrew from the study
      because of adverse events. CONCLUSION: Depot leuprolide was effective and safe
      for treating patients with chronic pelvic pain and clinically suspected
      endometriosis, confirming the potential of its empiric use in these patients.

PMID- 9916957
TI  - Cigarette smoking and effects on menstrual function.
AB  - OBJECTIVE: To examine the relationship between smoking and menstrual function,
      using biologic measures rather than self-report of menstrual cycle
      characteristics. METHODS: In a prospective study, 408 women collected urine daily
      for one to seven menstrual segments (cycles), maintained daily diaries, and
      completed detailed interviews. Smoking data from the diaries were averaged over
      each segment and verified by cotinine assay. Urine samples were analyzed for
      metabolites of steroid hormones to define the day of ovulation and various
      menstrual characteristics, including: 1) segment, follicular, luteal phase, and
      menses length, 2) variability, and 3) anovulation. RESULTS: Heavy smoking (at
      least 20 cigarettes per day) was associated with nearly four times the risk of
      short segment (less than 25 days) as was nonsmoking (adjusted odds ratio 3.8, 95%
      confidence limits 1.1, 12.7). Mean segment length was on average 2.6 days shorter
      with heavy versus no smoking (95% confidence limits 0.14, 5.0), due almost
      entirely to shortening of the follicular phase. Women who smoked an average of
      ten or more cigarettes per day had significantly more variable segment and menses
      lengths than nonsmokers. Based on small numbers, the data suggested that with
      greater smoking, there was a possible increased risk of anovulation and short
      luteal phase. Segments of exsmokers with ten or more pack-years of exposure were
      more likely to be short and have shorter luteal phases than those of never
      smokers. CONCLUSION: The effects found in this study of smoking on the menstrual
      cycle might explain in part associations of smoking with other reproductive
      endpoints, such as subfecundity and early menopause.

PMID- 9916958
TI  - Expression of adrenomedullin in the endometrium of the human uterus.
AB  - OBJECTIVE: Our purpose was to determine whether adrenomedullin is present in the
      human uterus. METHODS: We obtained specimens from five patients with leiomyoma
      and four patients with endometrial adenocarcinoma who were undergoing abdominal
      hysterectomy. Tissue sections were stained with antibody against adrenomedullin
      using an avidin-biotin-peroxidase complex technique. Total RNA from normal and
      cancerous endometrium, myometrium, and leiomyoma was prepared and analyzed by
      northern blot methodology. RESULTS: Sections stained with an antibody to
      adrenomedullin showed prominent expression of adrenomedullin in the normal and
      cancerous endometrial epithelial cells. Northern blot analysis showed that normal
      and cancerous endometrium expressed the messenger RNA (mRNA) for adrenomedullin
      and that the size of the mRNA transcript was 1.6 kilobases (kb). No significant
      difference was observed between the abundance of mRNA in normal and cancerous
      endometrium. CONCLUSION: The findings in this study demonstrated that both
      adrenomedullin protein and mRNA are present in normal and carcinomatous
      endometrium of the human uterus.

PMID- 9916959
TI  - Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid.
AB  - OBJECTIVE: To evaluate the therapeutic effect of photodynamic therapy on vulvar
      lichen sclerosus. METHODS: Twelve women with lichen sclerosus were enrolled in a
      prospective, single-arm pilot study. Four to 5 hours before photodynamic therapy,
      10 mL of a 20% solution of 5-aminolevulinic acid was applied topically to the
      vulva. Photodynamic therapy was administered with an irradiation of 80 J/cm2 at
      an irradiance of 40-70 mW/cm2. Light with a wavelength of 635 nm was delivered by
      an argon ion-pumped dye laser. The degree of pruritus was evaluated using a
      horizontal visual analog scale before and after 6-8 weeks, and patients were
      followed tri-monthly after photodynamic therapy. RESULTS: Two women underwent two
      cycles of photodynamic therapy, one underwent three cycles, and the remaining
      nine women underwent one cycle each. Treatment was tolerated moderately well,
      with eight patients not requiring any analgesia; three treated with opioids
      intravenously during the procedure, due to burning sensations; and one undergoing
      separation of adhesions under general anesthesia. Minimal local toxicity included
      vulvar erythema but no necrosis, sloughing, or scarring. No generalized cutaneous
      photosensitivity was present. Six to 8 weeks after photodynamic therapy, pruritus
      significantly improved in ten of the 12 women. A prolonged effect of photodynamic
      therapy was reported, with a mean of 6.1 months. CONCLUSION: Photodynamic therapy
      after topical application of 5-aminolevulinic acid produced statistically
      significant relief of symptoms of vulvar lichen sclerosus for an average of 6.1
      months with minimal side effects.

PMID- 9916960
TI  - A randomized trial of burch retropubic urethropexy and anterior colporrhaphy for
      stress urinary incontinence.
AB  - OBJECTIVE: In a randomized trial, we compared the success of Burch retropubic
      urethropexy to the modified anterior colporrhaphy for the treatment of genuine
      stress urinary incontinence. METHODS: Thirty-five patients with stress
      incontinence were randomly assigned to undergo Burch retropubic urethropexy or
      modified anterior colporrhaphy. Subjects had preoperative and 1-year
      postoperative physical examinations, multichannel urodynamic testing, 20-minute
      pad test, and subjective grading of incontinence severity with questionnaires.
      Data were evaluated using Fisher exact test, Wilcoxon two-sample test, logistic
      regression analysis, and analysis of variance. RESULTS: Objective cure 1 year
      postoperatively was significantly greater for the women treated by Burch
      retropubic urethropexy than by modified anterior colporrhaphy (16 of 18 [89%]
      versus five of 16 [31%], relative risk .15, 95% confidence interval .04, .59).
      Patients' subjective ratings of incontinence severity 1 year after surgical
      treatment were significantly lower in women who had Burch retropubic urethropexy.
      CONCLUSION: Burch retropubic urethropexy yields a significantly superior
      objective cure for genuine stress urinary incontinence than the modified anterior
      colporrhaphy in a randomized trial.

PMID- 9916961
TI  - Randomized comparison of intravenous nitroglycerin and magnesium sulfate for
      treatment of preterm labor.
AB  - OBJECTIVE: To compare the safety and efficacy of high-dose intravenous (IV)
      nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm
      labor. METHODS: Thirty-one women with preterm labor before 35 weeks' gestation
      were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis.
      Preterm labor was defined as the occurrence of at least two contractions in 10
      minutes, with cervical change or ruptured membranes. Acute tocolysis was defined
      as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g
      bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg
      bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was
      achievement of at least 12 hours of successful tocolysis. RESULTS: Thirty
      patients were available for analysis. There were no significant differences in
      gestational age, cervical dilation, or incidence of ruptured membranes between
      groups at the initiation of tocolysis. Successful tocolysis was achieved in six
      of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving
      magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures
      (nitroglycerin versus magnesium sulfate) were due to persistent contractions with
      cervical change or rupture of previously intact membranes (five of 16 versus two
      of 14), persistent hypotension (four of 16 versus none of 14), and other severe
      side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were
      more pronounced in patients who received nitroglycerin, and 25% of patients
      assigned to nitroglycerin treatment had hypotension requiring discontinuation of
      therapy. CONCLUSION: Tocolytic failures were more common with nitroglycerin than
      with magnesium sulfate. The hemodynamic alterations noted in patients receiving
      nitroglycerin, including a 25% incidence of persistent hypotension, might limit
      the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

PMID- 9916962
TI  - Modulation of the prostaglandin E receptor: a possible mechanism for infection
      induced preterm labor.
AB  - OBJECTIVE: To evaluate the modulatory effects of interleukin (IL)-1beta and
      prostaglandin (PG)E2 on the PGE2 receptor subtype EP1 in amnion cell cultures.
      METHODS: Amnion cell cultures were incubated in increasing concentrations of (IL)
      1beta or PGE2. Cultures were also incubated in high concentrations of IL-1beta
      and PGE2 in combination. Changes in EP1 receptor levels were evaluated by western
      and northern blot analysis. Culture fluid PGE2 levels were measured by enzyme
      linked immunosorbent assay. RESULTS: EP1 receptor protein levels decreased with
      increasing levels of PGE2 (r = -0.82, P < .05). EP1 receptor protein (r = 0.95, P
      < .05), EP1 mRNA (r = 0.95, P < .01), and culture fluid PGE2 levels (P < .01)
      were all increased after IL-1beta administration. EP1 receptor levels also
      increased approximately fourfold in response to IL-1beta incubation even in the
      presence of high agonist (PGE2) concentrations (P < .01). CONCLUSION: The results
      of this study show that IL-1beta might be involved in infection-induced preterm
      labor by interfering with the normal regulation of EP1 receptor levels and with
      the promotion of increased PGE2 production in amnion tissue.

PMID- 9916964
TI  - Three-dimensional structure of the smooth muscle in the term-pregnant human
      uterus.
AB  - OBJECTIVE: To identify the structural elements and describe the three-dimensional
      microanatomy of the term-pregnant human uterus. METHODS: Biopsy specimens were
      taken from the funduses and the lower uterine segments of two term-pregnant
      uteri. Tissue was sectioned serially and stained with Masson trichrome.
      Microscope images were captured with a digital camera, aligned, and computer
      processed. Computer-assisted three-dimensional reconstruction of structures was
      performed. RESULTS: Five structures were identified: 1) fasciculus-the
      macroscopic organization of myocytes and connective tissue, 2) cylindric bundle
      300+/-100-microm diameter cylinder of densely packed myocytes, 3) sheet-like
      bundle-densely packed sheet of myocytes, 4) fiber bundle-a loosely packed bundle
      of small numbers of myocytes, and 5) communicating bridge-a large cylindric
      bundle that bridges adjacent fasciculi. The cylindric bundles merged,
      dichotomized, and intertwined with each other and with sheet-like bundles.
      Essentially all myocytes except those in fiber bundles were contiguous.
      CONCLUSION: The microanatomy of the term-pregnant human uterus contains clearly
      defined structural elements. These structures merge with each other and
      potentially form an interlacing network, connecting the vast majority of the
      myocytes of the uterus in a contiguous pathway.

PMID- 9916963
TI  - Prostaglandin receptors in lower segment myometrium during gestation and labor.
AB  - OBJECTIVE: To determine if expression of relaxatory prostaglandin (PG) E2
      receptors (EP2 isoform) and contractile PG F receptors (FP isoform) changes
      during gestation and with labor in pregnant human myometrium. METHODS: Lower
      segment myometrium was removed at cesarean from four groups of parturients
      (preterm [28-36 weeks] or term [37-41 weeks], either in or not in labor, ten per
      group). Myometrial RNA was isolated and used for reverse transcription-polymerase
      chain reaction (PCR) analysis with specific primer sets for human smooth muscle
      protein calponin and PGEP2 or FP receptor isoform mRNA. Polymerase chain reaction
      products were electrophoresed on gels and visualized, band intensity was
      measured, and EP2 and FP receptor expression was normalized to calponin. RESULTS:
      Reverse transcription-PCR yielded products of expected sizes, and restriction
      enzyme cleavage confirmed identities. Prostaglandin EP2 receptor isoform mRNA
      expression (relative to calponin mRNA) was significantly greater in the preterm,
      no labor group (1.28+/-0.22, mean +/-standard error of the mean [SE]) compared
      with the term, no labor group (0.71+/-0.09) (P < .05 Student-Neuman-Kuels) and
      declined significantly with gestational age in patients not in labor (R = -.446,
      P = .001). Prostaglandin FP receptor isoform mRNA expression was significantly
      less in the term, no labor group (0.61+/-0.06) compared with all others (P < .02
      Student-Neuman-Kuels). Prostaglandin FP receptor expression declined
      significantly with gestational age in patients not in labor (R = -.646, P = .012)
      and increased significantly with labor at term. CONCLUSION: Changes in
      prostaglandin EP2 receptor isoform expression are consistent with influence on
      maintenance of quiescence. Labor at term is associated with a significant
      increase in FP receptor expression, consistent with influence on contraction. The
      balance between the two receptor isoforms might mediate myometrial contractility.

PMID- 9916965
TI  - Protection against preterm delivery in mice by urinary trypsin inhibitor.
AB  - OBJECTIVE: To investigate the precise mechanism by which urinary trypsin
      inhibitor suppresses cytokine production in the prevention of preterm delivery.
      METHODS: In vivo and in vitro studies were performed using ascites and peritoneal
      macrophages obtained on day 15 of pregnancy from female C3H/HeN mice that had
      been impregnated by B6D2F1 male mice. Lipopolysaccharide receptor, the
      intracellular signal transduction system, and nuclear factor-kappaB level were
      examined. RESULTS: In the in vivo study, we found that urinary trypsin inhibitor
      ameliorated the deterioration of intraperitoneal conditions induced by
      lipopolysaccharide (ie, increases in ascitic volume, peritoneal cell count, and
      tumor necrosis factor-alpha level) and caused a decrease in the binding of
      lipopolysaccharide to mouse macrophages. In the in vitro studies, urinary trypsin
      inhibitor decreased the binding capacity of lipopolysaccharide for its receptor,
      blocked the intracellular signal transduction induced by lipopolysaccharide, and
      decreased the nuclear factor-kappaB level. Increases were induced in the binding
      capacity of the macrophages for urinary trypsin inhibitor and its incorporation
      into them in the presence of lipopolysaccharide. CONCLUSION: We postulate that
      urinary trypsin inhibitor may suppress the production of inflammatory cytokines
      induced by lipopolysaccharide in mouse peritoneal macrophages through suppression
      of the lipopolysaccharide receptor, inhibition of the intracellular signal
      transduction system, and decrease in the nuclear factor-kappaB level.

PMID- 9916966
TI  - Interpregnancy interval and disparity in term small for gestational age births
      between black and white women.
AB  - OBJECTIVE: To examine the influence of interpregnancy interval on the elevated
      risk of term small for gestational age (SGA) births to black women. METHODS: This
      study is a secondary analysis of data from the Delivery Interview Program, a
      hospital-based cohort study of 12,718 women conducted at the Boston Hospital for
      Women from 1977 to 1980. The current analysis was limited to black and white
      parous women who gave birth to term infants during the study and whose last
      previous pregnancies had also resulted in term, live births. There were 578 black
      and 3400 white women who met these criteria. The rates of term SGA births for
      black and white women were calculated according to six interpregnancy intervals
      (6 or less, 6-12, 12-24, 24-36, 36-60, or longer than 60 months). Multiple
      logistic regression was used to control for confounding. RESULTS: The overall
      rate of term SGA births was 6.4% for black women compared with 3.9% for white
      women (relative risk [RR] 1.7, 95% confidence interval [CI] 1.2, 2.4). Black
      women were also more likely than white women to have interpregnancy intervals of
      6 months or less (9.2% black, 4.8% white; RR 1.9, 95% CI 1.4, 2.6). At every
      interpregnancy interval, black women had a higher rate of term SGA births than
      white women. After controlling for interpregnancy interval in a logistic
      regression analysis, the increased risk of SGA delivery among black women
      remained unchanged (odds ratio 1.7, 95% CI 1.1, 2.5). CONCLUSION: Although black
      women were more likely than white women to have SGA births and short
      interpregnancy intervals, differences in interpregnancy intervals between the
      races did not explain the disparity in term SGA births.

PMID- 9916967
TI  - The relation between inter-twin birth weight discordance and total twin birth
      weight.
AB  - OBJECTIVE: We tested the hypothesis that the frequency of growth discordance
      among twins is not related to the uterine capacity for carrying twins. METHOD: We
      counted and compared the frequencies of birth weight discordance of more than 25%
      in an unlike-sexed twin cohort (n = 1244) and in a population-based twin cohort
      (n = 7570) across the deciles of the total twin birth weight (twin A + twin B)
      distribution. The birth order of the heavier twin was noted. RESULTS: Similar
      frequencies of discordant pairs were found in both cohorts (11% and 12%,
      respectively; Mantel-Haenszel chi2 test: P = .131, odds ratio (OR) 0.9, 99%
      confidence interval (CI) 0.67, 1.11; Woolf test for heterogeneity: two-tailed P =
      .472). In the discordant pairs, twin A was considerably more often the heavier
      twin in all birth weight deciles (unlike-sexed cohort: P < 10(-8), OR 5.9, 99% CI
      3.0, 11.7; population-based cohort: P < 10(-8), OR 3.1, 99% CI 2.3, 4.0), and in
      both cohorts (inter-cohort difference: P = .109, OR 1.4, 99% CI 0.83, 2.32). Both
      cohorts showed a similar nonlinear trend: given that X = decile order,
      discordance decreased as a function of 22.0 - 6.54 ln[X] for the unlike-sexed
      twins cohort and 23.0 - 8.18 ln[X] for the population-based cohort, with r values
      of 0.967. CONCLUSION: The more favorable the uterine milieu for carrying twins,
      the smaller the likelihood of discordant twin growth. Birth order of the heavier
      twin appears to be an integral part of the discordance phenomenon. The similarity
      of the cohorts suggests that these conclusions are valid for both like and unlike
      sexed twins.

PMID- 9916969
TI  - Telomerase and proliferative activity in placenta from women with and without
      fetal growth restriction.
AB  - OBJECTIVE: To analyze telomerase and proliferative activity in placenta from
      women with and without fetal growth restriction (FGR). METHODS: Telomerase
      activity was analyzed in 30 first-trimester chorionic villi specimens (group A)
      and in 28 second- and third-trimester placenta specimens (group B) from women
      without FGR. Telomerase activity also was analyzed in 11 placenta specimens from
      women with asymmetric FGR (group C). The proliferative activity of these 69
      specimens was assessed by immunohistochemical staining, using the MIB-1
      monoclonal antibody. RESULTS: Telomerase activity was detected in 28 (93.3%) of
      30 chorionic villi specimens and in 18 (64.3%) of 28 placenta specimens without
      FGR. In contrast, no telomerase activity was exhibited in the placenta specimens
      from any of the 11 women with asymmetric FGR by telomeric repeat amplification
      protocol assay. Telomerase activity also was detected by in situ telomeric repeat
      amplification protocol assay in trophoblastic cells from women without FGR but
      not in trophoblastic cells from women with asymmetric FGR. Thus, telomerase
      activity was detected significantly more often in groups A and B than in group C
      (P < .01). The rate of proliferative activity, evident as positive MIB-1 staining
      in trophoblastic cells, in groups A and B (28.1+/-1.7% and 7.0 +/-2.9%,
      respectively) was significantly higher than that in group C (1.9+/-0.6%; P <
      .01). CONCLUSION: Telomerase and proliferative activity were minimal in placenta
      from women with asymmetrical FGR, suggesting placental senescence with
      asymmetrical FGR.

PMID- 9916968
TI  - Association between bacterial vaginosis and fetal fibronectin at 24-29 weeks'
      gestation.
AB  - OBJECTIVE: To investigate the relationship between fetal fibronectin and
      bacterial vaginosis, which are associated with an increased risk for preterm
      delivery. METHODS: Researchers for the Pregnancy, Infection and Nutrition Study,
      a cohort study of pregnant women at three central North Carolina sites, collected
      genital tract specimens from all enrolled women between 24 and 29 weeks'
      gestation. Among women with last menstrual periods between March 10, 1995, and
      August 15, 1996, 868 pregnancies were eligible for this analysis. Fetal
      fibronectin was assessed by a dipstick immunoassay kit. Bacterial vaginosis was
      evaluated by Nugent-scored, Gram-stained vaginal smears (scores of 7-10
      considered positive). RESULTS: Overall, 6.3% of women had positive fetal
      fibronectin test results, and 18.8% had bacterial vaginosis. The unadjusted
      relative risk (RR) of fetal fibronectin-positivity comparing women with bacterial
      vaginosis to those without bacterial vaginosis was 1.6 (95% confidence interval
      [CI] 1.1, 2.5). Using multiple logistic regression to adjust for race, maternal
      age, parity, and location of care, women who had bacterial vaginosis and smoked
      at the time of recruitment were at substantially increased risk of fetal
      fibronectin-positivity (RR 7.8, 95% CI 2.2, 27.8) compared with smokers without
      bacterial vaginosis. Among nonsmokers, bacterial vaginosis was not associated
      with fetal fibronectin-positivity (RR 1.0, 95% CI 0.4, 2.4). These results were
      essentially unchanged after adding the requirement of vaginal pH exceeding 4.5 to
      the bacterial vaginosis definition. CONCLUSION: Fetal fibronectin was associated
      positively with bacterial vaginosis, but only among women who smoked. These
      results might provide clues as to the biologic relationship between smoking,
      infection, and preterm delivery.

PMID- 9916970
TI  - Monoamniotic twins: case series and proposal for antenatal management.
AB  - OBJECTIVE: To present a case series of antenatally suspected monoamniotic twin
      gestations managed by a similar set of guidelines. METHODS: Eight women with
      antenatally suspected monoamniotic twins were identified between 1994 and 1996 in
      a single perinatal referral area. All were diagnosed sonographically. Management
      included serial ultrasound studies, frequent nonstress testing, and weekly
      steroid therapy. Elective cesarean delivery was recommended at 32 weeks unless
      obstetrically indicated at an earlier age. RESULTS: Monochorionic monoamniotic
      twins were confirmed at delivery in six women, and one had a pseudomonoamniotic
      twin. One woman was found to have a monochorionic diamniotic pregnancy at
      delivery. Of the eight women, three were delivered by elective cesarean at 32
      weeks, including the falsely diagnosed case. Three were delivered before 32 weeks
      because of nonreassuring fetal testing. One was delivered at 25 weeks secondary
      to hemolysis, elevated liver enzymes, low platelets, and disseminated
      intravascular coagulation. One was delivered at 33 weeks, after declining
      elective delivery at 32 weeks, because of death of one twin and nonreassuring
      testing of the other twin. Morbidity among the live-born infants included severe
      bronchopulmonary dysplasia (25-week twins), large-bowel perforation (30-week
      infant), and respiratory distress syndrome and mild bronchopulmonary dysplasia
      (one 32-week pair). CONCLUSION: Monoamniotic twin pregnancies can be diagnosed
      reliably by ultrasound alone in most cases. Frequent antenatal testing may show
      signs of cord compression that may prompt delivery but will not prevent sudden
      fetal death. Fetal death can occur at greater than 32 weeks' gestation despite
      intensive fetal surveillance. Elective preterm delivery could be considered to
      eliminate the uncertain risk of fetal death.

PMID- 9916972
TI  - Current concepts of fetal growth restriction: part II. Diagnosis and management.
AB  - OBJECTIVE: To update diagnostic concepts and management strategies of fetal
      growth restriction (FGR). DATA SOURCE: An English literature search was conducted
      for pertinent articles related to FGR from 1976 to 1997 including original
      research articles, review articles, and book chapters. METHODS OF STUDY
      SELECTION: In part II, clinical studies involving both diagnostic and therapeutic
      approaches to the management of FGR were included. Throughout the study period,
      the evolution of concepts is demonstrated. TABULATION, INTEGRATION, AND RESULTS:
      Diagnostic methods including two- and three-dimensional ultrasound for diagnosis
      of fetal structural abnormalities, organ volumetry, and estimating fetal weight
      are presented. Clinical tools to assess fetal well-being such as nonstress tests,
      contraction stress tests, biophysical profile scores, and Doppler blood flow
      velocimetry of fetal circulation and funicentesis are discussed. Correlations
      between these indirect fetal evaluations and fetal blood biochemical parameters
      obtained by funicentesis are also reviewed. Finally, various therapeutic
      approaches, especially timing of delivery of growth-restricted fetuses, are
      formulated. CONCLUSION: We suggest that both diagnostic and therapeutic
      approaches to FGR should be modified. With the current development of technology,
      newly available three-dimensional ultrasound might offer more precise diagnostic
      data than conventional two-dimensional ultrasonography in the near future. From
      current concepts of pathophysiology of FGR, morphometric measurement abnormality
      alone should not be a basis for intervention. Combined use of morphometric
      measurements and functional evaluation tests and good clinical judgment using
      flexibility and individualization are the key elements in successful management
      of FGR.

PMID- 9916971
TI  - High-resolution imaging of gynecologic neoplasms using optical coherence
      tomography.
AB  - BACKGROUND: A modality capable of imaging the female reproductive tract, at or
      near the cellular level, could lead to the detection of diseases at earlier
      stages than currently possible. Optical coherence tomography achieves high
      resolutions in the cellular range (4-20 microm) and could accomplish that level
      of detection. METHOD: Optical coherence tomography imaging of gynecologic tissue
      was studied in vitro on normal and neoplastic human cervical and uterine tissue.
      EXPERIENCE: The structures of the normal ectocervix and endocervix, including
      epithelium, basal membrane, and glands, were identified clearly. These findings
      were compared with changes associated with carcinoma in situ and invasive
      carcinoma. The optical coherence tomography images of the uterus also showed
      changes between microstructural features of normal tissue and endometrial
      adenocarcinoma. CONCLUSION: Optical coherence tomography of tissue
      microstructures showed potential for powerful, minimally invasive assessment of
      the female reproductive tract at a resolution greater than any current clinical
      imaging method.

PMID- 9916973
TI  - Oocyte donors as gynecologic teaching associates.
AB  - OBJECTIVE: To fulfill the need for gynecologic teaching associates for an
      expanded pelvic examination module for third-year medical students, we sought
      women who were able to provide feedback to medical students. Oocyte donors were
      hypothesized as a useful potential pool of gynecologic teaching associates.
      METHODS: Gynecologic teaching associates were recruited from a pool of women who
      were involved in our oocyte donor program. Students were evaluated on a scale of
      1 (best) to 5 (worst) on their performance on the pelvic examination by
      themselves (n = 91), by the gynecologic teaching associate (n = 10), and by the
      supervising faculty (n = 6). Students were shown their evaluations, and these
      were reviewed at the end of the session to provide students with immediate
      feedback. RESULTS: Students consistently ranked their skills lower than either
      the gynecologic teaching associate or supervising faculty member for all four
      categories evaluated (communication skills, technical skills, professional
      demeanor, and overall performance) (P < .001). Students gave their communications
      skills the highest mean rankings, whereas gynecologic teaching associates gave
      them the lowest. The highest correlation and agreement between pairs of
      evaluators were between the gynecologic teaching associate and the supervising
      faculty member. Gynecologic teaching associates and faculty members also were
      more likely to praise the students' performance in written comments (chi2 58.2, P
      < .001), whereas no student found anything praiseworthy in his or her
      performance. CONCLUSION: Oocyte donors represent a useful pool of potential
      gynecologic teaching associates. They provide important feedback to students.
      Their evaluation of the proficiency of the student correlates well with that of
      the supervising faculty member.

PMID- 9916974
TI  - Understanding and managing the emotional reactions to a miscarriage.
AB  - The experience of loss following a miscarriage tends not to be recognized or
      validated by many key people in a woman's life, including her physician. Surveys
      of patient satisfaction following miscarriage indicate a high percentage of anger
      and dissatisfaction with the medical care received. The main complaints center on
      physician insensitivity and lack of opportunity to discuss the personal
      significance of the loss. Satisfaction was highest when there was a follow-up
      appointment soon after the loss, at which time answers to the almost universally
      asked questions of why the miscarriage occurred and whether it would happen again
      were addressed, and sufficient time was allowed to focus on the patient's
      feelings. The most likely emotions to be present relate to a relatively brief
      period of loss characterized by grief, dysphoria, and anxiety. The risk of a more
      intense or longer lasting distress is likely to occur if the woman strongly
      desired the pregnancy, waited a long time to conceive, has no living children,
      had elective abortions or other losses in the past, had few warning signs that a
      loss might occur, experienced the loss relatively late in the pregnancy, has
      little social support, or has a history of coping poorly. When there is an
      elevated level of distress, it tends to take the form of depressive and anxiety
      disorders, often accompanied by feelings of guilt and worries about future
      reproductive competence. In addition to validating the significance and nature of
      the patient's feelings, a physician can help the patient develop rituals to
      facilitate grieving and plan for anticipated, stressful occasions.

PMID- 9916975
TI  - High third-trimester ferritin concentration: associations with very preterm
      delivery, infection, and maternal nutritional status.

PMID- 9916976
TI  - Rectally administered misoprostol for the treatment of postpartum hemorrhage
      unresponsive to oxytocin and ergometrine: a descriptive study.

PMID- 9916977
TI  - The isolated choroid plexus cyst.

PMID- 9916978
TI  - If tocolytic magnesium sulfate is associated with excess total pediatric
      mortality, what is its impact?

PMID- 9916979
TI  - A multicenter randomized comparison of laparoscopically assisted vaginal
      hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates.

PMID- 9916980
TI  - A multicenter randomized comparison of laparoscopically assisted vaginal
      hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates.

PMID- 9916981
TI  - Incidence and predictors of cervical dysplasia in patients with minimally
      abnormal Papanicolaou smears.

PMID- 9916982
TI  - Hemolytic disease of the fetus: a comparison of the Queenan and extended Liley
      methods.

PMID- 9916983
TI  - Signal transduction pathways that regulate cell survival and cell death.
AB  - Apoptosis or programmed cell death (PCD) is a physiological process critical for
      organ development, tissue homeostasis and elimination of defective or potentially
      dangerous cells in complex organisms. Apoptosis permits cell death without a
      concomitant inflammatory response in the surrounding tissues. The process of
      apoptosis depends on the reception of multiple extracellular and intracellular
      signals, integration and amplification of these signals by second messengers and
      finally, activation of the death effector proteases. Defects in control of
      apoptotic pathways may contribute to a variety of diseases including cancer,
      autoimmune and neurodegenerative conditions and AIDS. While many components of
      the regulatory network controlling apoptosis have been defined, the mechanisms of
      action and patterns of interaction of these factors remain controversial. This
      article summarizes some of the known aspects of signaling pathways involved in
      apoptosis.

PMID- 9916984
TI  - Mechanisms and control of programmed cell death in invertebrates.
AB  - Apoptosis is a morphologically distinct form of programmed cell death that plays
      important roles in development, tissue homeostasis and a wide variety of
      diseases, including cancer, AIDS, stroke, myopathies and various
      neurodegenerative disorders (see Thompson (1995) for review). It is now clear
      that apoptosis occurs by activating an intrinsic cell suicide program which is
      constitutively expressed in most animal cells, and that key components of this
      program have been conserved in evolution from worms to insects to man. Genetic
      studies of programmed cell death in experimentally highly accessible invertebrate
      model systems have provided important clues about the molecular nature of the
      death program, and the intracellular mechanisms that control its activation. This
      review summarizes some of the key findings in this area, but also touches on some
      of the many unresolved questions and challenges that remain.

PMID- 9916985
TI  - Bcl-2 family proteins.
AB  - Bcl-2 family proteins serve as critical regulators of pathways involved in
      apoptosis, acting to either inhibit or promote cell death. Altered expression of
      these proteins occurs commonly in human cancers, contributing to neoplastic cell
      expansion by suppressing programmed cell death and extending tumor cell life
      span. Moreover, because chemotherapeutic drugs typically exert their cytotoxic
      actions by inducing apoptosis, the ultimate efficacy of most anticancer drugs can
      be heavily influenced by the relative levels and state of activation of members
      of the Bcl-2 family. The question of how Bcl-2 family proteins function remains
      debatable, but new findings are shaping our impressions of these multi-functional
      proteins and revealing the details of how these proteins participate in the
      regulation of cell life and death.

PMID- 9916986
TI  - Caspases: the proteases of the apoptotic pathway.
AB  - Apoptosis, a morphologically defined form of physiological cell death, is
      implemented by a death machinery whose executionary arm is a family of cysteine
      proteases called caspases. These death proteases are part of a proteolytic
      caspase cascade that is activated by diverse apoptotic stimuli from outside and
      inside of the cell. The cell death machinery is evolutionarily conserved and
      composed of caspases and their regulatory components that include activators and
      repressors. These key components of the death machinery are linked to signaling
      pathways that are activated by either ligation of death receptors expressed at
      the cell surface or intracellular death signals. Caspases are normally present in
      the cell as proenzymes that require limited proteolysis for activation of
      enzymatic activity. Recent studies suggest that the basic mechanism of caspase
      activation is conserved in evolution. Binding of initiator caspase precursors to
      activator molecules appears to promote procaspase oligomerization and
      autoactivation. Enzymatic activation of initiator caspases leads to proteolytic
      activation of downstream (effector) caspases and cleavage of a number of vital
      proteins, resulting in the orderly demise and removal of the cell.

PMID- 9916987
TI  - The inhibitors of apoptosis (IAPs) and their emerging role in cancer.
AB  - The inhibitor of apoptosis protein family has been characterized over the past 5
      years, initially in baculovirus and more recently in metazoans. The IAPs are a
      widely expressed gene family of apoptotic inhibitors from both phylogenic and
      physiologic points of view. The diversity of triggers against which the IAPs
      suppress apoptosis is greater than that observed for any other family of
      apoptotic inhibitors including the bcl-2 family. The central mechanisms of IAP
      apoptotic suppression appear to be through direct caspase and pro-caspase
      inhibition (primarily caspase 3 and 7) and modulation of and by the transcription
      factor NF-kappaB. Although evidence for a direct oncogenic role for the IAPs has
      yet to be delineated, a number of lines of evidence point towards this class of
      protein playing a role in oncogenesis. The strongest evidence for IAP involvement
      in cancer is seen in the IAP called survivin. Although not observed in adult
      differentiated tissue, survivin is present in most transformed cell lines and
      cancers tested to date. Survivin has been shown to inhibit caspase directly and
      apoptosis in general, moreover survivin protein levels correlate inversely with 5
      year survival rates in colorectal cancer. Recent data has also implicated
      survivin in cell cycle control. The second line of evidence for IAP involvement
      in cancer comes from their emerging role as mediators and regulators of the anti
      apoptotic activity of v-Rel and NF-kappaB transcription factor families. The IAPs
      have been shown to be induced by NF-kappaB or v-Rel in multiple cell lines and
      conversely, HIAP1 and HIAP2 have been shown to activate NF-kappaB possibly
      forming a positive feed-back loop. Overall a picture consistent with an IAP role
      in tumour progression rather than tumour initiation is emerging making the IAPs
      an attractive therapeutic target.

PMID- 9916988
TI  - Modulation of life and death by the TNF receptor superfamily.
AB  - The tumor necrosis factor receptor (TNFR) superfamily represents a growing
      family, with over 20 members having been identified thus far in mammalian cells.
      These proteins share significant homologies in their extracellular ligand binding
      domains and intracellular effector (death) domains. These receptors appear to
      transmit their signals via protein-protein interactions, which convey either a
      death or survival signal. Isolation and characterization of death domain
      containing proteins (TRADD, FADD/MORT-1, RIP), TRAF domain containing proteins
      (TRAF1-6) as well as new members and adaptor proteins such as DAXX have provided
      new insights to our understanding of signaling mechanisms associated with this
      family of receptors. While the death signals seem to be associated with the
      activation of both the caspase and JUN kinase pathways, the survival signals are
      mediated via the activation of the NF-kappaB pathway.

PMID- 9916989
TI  - CD95 mediated T cell apoptosis and its relevance to immune deviation.
AB  - The CD95/CD95L pair plays a manifold role in regulating life and death in the
      function of the immune system. Examples include CD95/CD95L acting as cytotoxic
      CD8+ T cell effector molecules, or functioning on CD4+ T helper cells to maintain
      peripheral tolerance or reestablishing homeostasis. Current understanding of the
      CD95 signaling pathway reveals several potential regulatory targets, acting both
      receptor proximally and distally, that can terminate or amplify the receptor's
      signal. The important and possibly non-redundant role of CD95 is highlighted both
      in how deficiencies in functional CD95 or its ligand manifest themselves in
      autoimmune syndromes, and how uncontrolled cell death results in insufficient, or
      inappropriate immune responses against immune challenge. This review examines
      CD95-mediated signal transduction, and the effect preferential apoptosis of T
      helper cell subsets has on immune system biasing.

PMID- 9916990
TI  - Stress signals for apoptosis: ceramide and c-Jun kinase.
AB  - Mammalian systems respond to environmental stress by either adapting or
      undergoing programmed cell death. While there is general agreement that the
      caspase family of proteases serve as the effectors of the apoptotic death
      response, the signaling apparatus involved in the decision to activate the
      caspase system is less clear. In the past few years, the sphingomyelin and c-Jun
      Kinase (JNK)/Stress-activated Protein Kinase (SAPK) pathways have been linked to
      the death response in many cellular systems. These signaling systems are found
      throughout the animal kingdom, and ceramide signaling is conserved through yeast.
      Since yeast do not undergo apoptosis, the sphingomyelin pathway appears
      evolutionarily older than the caspase-mediated death programs. While recent
      reviews by several groups have broadly surveyed ceramide signaling in apoptosis,
      this paper examines the role of sphingomyelinases and the JNK/SAPK pathway in
      coordinate signaling of apoptosis.

PMID- 9916991
TI  - Roles for p53 in growth arrest and apoptosis: putting on the brakes after
      genotoxic stress.
AB  - The tumor suppressor gene p53 plays a major role in regulation of the mammalian
      cellular stress response, in part through the transcriptional activation of genes
      involved in cell cycle control, DNA repair, and apoptosis. Many factors
      contribute to control of the activation of p53, and the downstream response to
      its activation may also vary depending on the cellular environment or other
      modifying factors in the cell. The complexity of the p53 response makes this an
      ideal system for application of newly emerging rapid throughput analysis
      techniques and informatics analysis.

PMID- 9916992
TI  - The role of ATM in DNA damage responses and cancer.
AB  - Ataxia-telangiectasia (AT) is a complex, autosomal recessive disorder
      characterized by cerebellar ataxia, believed to result from progressive
      neurodegeneration, and telangiectasia, dilation of blood vessels within the eyes
      and parts of the facial region. AT patients suffer from recurrent infections
      caused by both cellular and humoral immune deficiencies and as a population, are
      significantly predisposed to cancer, particularly lymphomas and leukemias. Early
      attempts at treating these malignancies with radiotherapy revealed another
      hallmark of AT, a profound hypersensitivity to the cytotoxic effects of ionizing
      radiation (IR) which is recapitulated at the cellular level in culture.
      Predisposition to cancer and radiosensitivity observed in AT has been linked to
      chromosomal instability, abnormalities in genetic recombination, and defective
      signaling to programmed cell death and several cell cycle checkpoints activated
      by DNA damage. These earlier observations predicted that the gene defective in AT
      may encode a protein which plays a crucial role in sensing DNA damage and
      transducing signals that promote cell survival. Through the combined efforts of
      linkage analysis and positional cloning, a single gene was identified on
      chromosome 11q22-33 by Shiloh and colleagues and was found to be mutated in all
      four complementation groups previously characterized in cell lines derived from
      AT patients (Savitsky et al., 1995a,b). The predicted ATM gene product shows
      considerable homology to an emerging family of high molecular weight,
      phosphatidylinositol-3 kinase (PI-3 K)-related proteins involved in eukaryotic
      cell cycle control, DNA repair, and DNA recombination (Zakian, 1995). This
      landmark discovery has triggered a resurgence of biochemical and genetic studies
      focusing on ATM function which has brought forth insights regarding ATM activity
      and its role in DNA damage signaling.

PMID- 9916993
TI  - Determination of cell fate by c-Abl activation in the response to DNA damage.
AB  - The cellular response to DNA damage includes growth arrest and activation of DNA
      repair. Certain insights into how DNA damage is converted into intracellular
      signals that control the genotoxic stress response have been derived from the
      finding that the c-Abl protein tyrosine kinase is activated by ionizing radiation
      and other DNA-damaging agents. c-Abl associates with the DNA-dependent protein
      kinase (DNA-PK) and is activated by DNA-PK-dependent phosphorylation. The ataxia
      telangiectasia mutated (ATM) gene product also contributes to c-Abl activation.
      The demonstration that c-Abl binds to p53, induces the transactivation function
      of p53 and activates p21 expression has supported involvement of c-Abl in
      regulation of the p53-dependent G1 arrest response. Interaction between c-Abl and
      the Rad51 protein has also provided support for involvement of c-Abl in
      recombinational repair of DNA strand breaks. Defects in G1 arrest and repair
      predispose to replication of damaged templates and, in the event of irreparable
      DNA lesions, induction of apoptosis. The available evidence indicates that c-Abl
      effects a proapoptotic function by a mechanism largely independent of p53. c-Abl
      also functions as an upstream effector of the proapoptotic JNK/SAPK and p38 MAPK
      pathways. In addition, c-Abl-dependent inhibition of PI 3-kinase contributes to
      the induction of apoptosis. The findings thus suggest that, in response to
      genotoxic stress, c-Abl functions in determining cell fate, that is growth arrest
      and repair or induction of apoptosis. The physiologic function of c-Abl may
      reside in control of the cellular response to DNA strand breaks that occur during
      DNA replication, genetic recombination and gene rearrangements.

PMID- 9916994
TI  - MyD genes in negative growth control.
AB  - Two interrelated cellular processes are invoked simultaneously upon induction of
      differentiation, the regulated progression of cells through successive stages of
      cell differentiation and growth inhibition which ultimately leads to growth
      arrest. In tissues with rapid cell turnover terminally differentiated cells
      undergo programmed cell death. Terminal differentiation, thus, represents one
      form of negative growth control. It was surmised that the molecular engine which
      drives the differentiation process forward requires induction of positive
      regulators of terminal cell differentiation, to be found among differentiation
      primary response genes, as well as suppression of negative regulators, which
      correspond to genes which control cellular growth. This line of thought has
      prompted the isolation of myeloid differentiation primary response (MyD) genes
      activated in the absence of de novo protein synthesis, upon IL-6 induced terminal
      differentiation of murine M1 myeloblastic leukemia cells, where the cells growth
      arrest and ultimately undergo programmed cell death. As delineated in this review
      many of the genes identified as MyD genes, including both known genes [IRF-1, (AP
      1)Fos/Jun.EGR-1] and novel ones (MyD88, MyD116, MyD118), turned out to play a
      role in negative growth control, including growth suppression and apoptosis, in
      many cell types, of both hematopoietic and non hematopoietic origins.

PMID- 9916995
TI  - Death associated proteins (DAPs): from gene identification to the analysis of
      their apoptotic and tumor suppressive functions.
AB  - The process of apoptosis (programmed cell death) has become the subject of
      intensive and extensive research over the past few years. Various approaches are
      being used to identify and study genes which function as positive mediators of
      apoptosis. Here, we address a novel approach of gene cloning aimed at isolating
      intracellular death promoting genes by utilizing a functional screen. This
      method, called TKO, was based on transfection of cells with an anti-sense cDNA
      library, followed by the selection of transfectants which survived in the
      continuous presence of a killing cytokine-interferon-gamma. It led to the
      identification of five novel apoptotic genes and to the finding that a known
      protease-cathepsin D, is actively recruited to the death process. The five novel
      apoptotic genes (named DAP genes for: Death Associated Proteins) code for
      proteins which display a diverse spectrum of biochemical activities. The list
      comprises a novel type of calcium/calmodulin-regulated kinase which carries
      ankyrin repeats and a death domain (DAP-kinase), a nucleotide-binding protein
      (DAP-3), a small proline-rich cytoplasmic protein (DAP-1), and a novel homolog of
      the eIF4G translation initiation factor (DAP-5). Extensive studies proved that
      these genes are critical for mediating cell death initiated by interferon-gamma,
      and in some of the tested cases also cell death induced by Fas/APO-1, TNF-alpha,
      and a detachment from extracellular matrix. Moreover, one of these genes, DAP
      kinase, was recently found to display strong tumor suppressive activities,
      coupling the control of apoptosis to metastasis. The advantage of functional
      approaches of gene cloning is that they select the relevant rate limiting genes
      along the death pathways in a complete unbiased manner. As a consequence, novel
      targets and unpredicted mechanisms emerged. A few examples illustrating this
      important point will be discussed. One relates to the calcium/calmodulin
      dependent DAP-kinase, which is localized to the actin microfilaments. It was
      found that the correct localization of DAP-kinase to the microfilament network
      was critical for the execution of the apoptotic process, and more specifically
      for the disruption of the stress fibers--a typical hallmark of apoptosis. Another
      important breakthrough step in our understanding of apoptotic processes relates
      to the identification and analysis of the DAP-5 gene. The structure/ function
      features of this novel translation regulator resemble the proteolytically cleaved
      eIF4G which appears in cells upon infection with some RNA viruses and which
      directs cap-independent translation. Thus, the rescue of DAP-5 highlighted the
      importance of regulation of protein translation in certain apoptotic systems.
      Finally, the isolation of cathespin D by our method suggests that lysosomal
      proteases are recruited during apoptosis, in addition to the well known caspase
      family of proteases, and that a unique pattern of regulation affecting the
      processing of this protease takes place. The major challenge now is to analyse
      how these diverse DAP gene activities constitute biochemical pathway(s) leading
      to programmed cell death, and what is their functional position with respect to
      other known positive mediators and suppressors of apoptosis such as the Bcl2 and
      caspase family members.

PMID- 9916996
TI  - Mechanisms of cell death in hypoxia/reoxygenation injury.
AB  - Investigation of death pathways during cell injury in vivo caused by ischemia and
      reperfusion is of clinical importance, but technically difficult. Heterogeneity
      of cell types, differences between organ systems, diversity of death paradigms
      and exacerbation of tissue damage caused by inflammation are only some of the
      variables that need to be taken into account. With respect to the identification
      of necrosis and apoptosis in affected organs, technical issues related to
      preparation artifacts, occurrence of internucleosomal DNA cleavage in necrotic as
      well as apoptotic cells and other overlaps in death pathways bear consideration.
      In that caspase independent as well as caspase dependent processes cause cell
      death and that caspase inhibitors can act as anti-inflammatory agents, evaluation
      of ischemic death mechanisms in parenchymal cells needs to be performed with
      caution. When the effects of inflammation are removed by appropriate in vitro
      studies using purified or cultured cells, several mitochondrial factors that lead
      to cell death can be studied. Substantial evidence exists for the participation
      of electron transport defects, mitochondrial permeability transitions (MPT) and
      release of cytochrome c from mitochondria, effected by pro-apoptotic proteins
      such as Bax. The anti-apoptotic protein Bcl-2 exerts an overriding protective
      role in this type of injury by preserving mitochondrial structure and function.
      In contrast, caspase inhibitors cannot offer long-term protection to ischemically
      injured parenchymal cells regardless of how effectively they can inhibit
      apoptotic events, if the cells have suffered permanent mitochondrial damage
      impairing respiration.

PMID- 9916997
TI  - The proto-oncogene c-myc and apoptosis.
AB  - Deregulated expression of c-Myc not only promotes proliferation, but also can
      either induce or sensitize cells to apoptosis. Inappropriate expression of c-Myc
      under conditions which inhibit growth and down-regulate endogenous c-Myc
      expression, including serum deprivation and exposure to cytotoxic agents
      including the anticancer agents vinblastine, etoposide, Ara-C, and nocodazole,
      usually results in programmed cell death in many different cell types. Also,
      inappropriate Myc expression is associated with an apoptotic response elicited by
      induction of differentiation. The proapoptotic property of c-Myc requires an
      intact N-terminal transactivation domain and bHLHZip domain, as well as
      interaction with Max, thereby implicating c-Myc target genes in this apoptotic
      process. Although some target genes, namely cdc25A and ODC, have been shown to
      participate in Myc-mediated apoptosis, no target gene has yet been identified
      which is essential for this apoptotic response. It is possible that the response
      of cells inappropriately expressing c-Myc is due not only to the growth arrest
      signals per se, but also to signals elicited by specific growth inhibitors in the
      context of a particular biological setting. Also regulating the response of the
      cells is expression of other oncogenes and tumor suppressor genes, as well as
      paracrine and autocrine survival factors. Apoptosis associated with inappropriate
      Myc expression limits the tumorigenic effect of the c-myc proto-oncogene.
      Mechanisms which inhibit apoptosis should enhance or promote tumorigenesis.

PMID- 9916998
TI  - Radiosensitization and apoptosis.
AB  - The toxicity of radiation to living tissues was discovered soon after the
      discovery of radioactivity itself and this toxicity is the basis for cancer
      therapy with radiation. Although this mode of therapy is often effective, its
      success is far from assured. One major difficulty in the implementation of
      radiotherapy is that normal tissues are also sensitive to killing by radiation so
      that treatment is often limited by the tolerance of normal tissues for radiation.
      Thus methods that sensitize tumor cells while sparing normal tissues could
      potentially lead to greater success with radiation as a therapy. Oncogenes are
      frequently altered in tumors, but are not in normal tissue making them potential
      targets for altering radiosensitivity and apoptosis in tumors.

PMID- 9916999
TI  - Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative
      control of cell growth.
AB  - The retinoblastoma family of proteins, also known as pocket proteins, includes
      the product of the retinoblastoma susceptibility gene and the functionally and
      structurally related proteins p107 and p130. Pocket proteins control growth
      processes in many cell types, and this has been linked to the ability of pocket
      proteins to interact with a multitude of cellular proteins that regulate gene
      expression at various levels. By regulating gene expression, pocket proteins
      control cell cycle progression, cell cycle entry and exit, cell differentiation
      and apoptosis. This review will focus on the mechanisms of regulation of pocket
      proteins and how modulation of pocket protein levels and phosphorylation status
      regulate association with their cellular targets. The coordinated regulation of
      pocket proteins provides the cells with a competence mechanism for passage
      through certain cell growth and differentiation transitions.

PMID- 9917000
TI  - Mouse models in tumor suppression.
AB  - Genetic lesions found in tumors are often targeted to the negative growth
      regulatory tumor suppressor genes. Much of our understanding of tumor suppressor
      gene function is derived from experimental manipulations in cultured cells.
      Recently, however, the generation of mice with germ line tumor suppressor gene
      mutations through gene targeting in embryonic stem cells has provided another
      dimension by allowing experimental studies of tumor suppressor function in an
      organismal context. Novel insights into the role of tumor suppressors in
      development, differentiation, cell cycle control, and tumor suppression have been
      obtained from the studies on these 'knockout' mice. In addition, such mice may
      serve as disease models for humans with inherited cancer predisposition
      syndromes. Perhaps the greatest advantage of many of the mouse tumor suppressor
      models is that they facilitate study of the roles of tumor suppressor gene loss
      in tumor initiation and progression in vivo. Moreover, derivation of primary
      cells from tumor suppressor-deficient mice has provided an important resource for
      in vitro studies on the role of targeted genes in cell cycle regulation, DNA
      damage response, regulation of apoptotic pathways, and preservation of genomic
      stability. In this review, we discuss some of the mechanistic insights provided
      by tumor suppressor-deficient mice and their utility as models for human cancer
      syndromes.

PMID- 9917001
TI  - S19159, a modulator of neurite outgrowth produced by the ascomycete Preussia
      aemulans. I. Producing strain, fermentation, isolation and biological activity.
AB  - A modulator of neurite outgrowth, designated S19159, was isolated from the
      fermentation broth of fungal strain 19159. This fungus was identified as the
      loculoascomycete, Preussia aemulans (Rehm) von Arx. In the presence of S19159,
      the number of neurites extending from the cell bodies of cerebral cortical
      neurons was markedly reduced. The effect of S19159 was observed specifically in
      neurons from the central nervous system. The compound exhibited similar
      activities on cultured cortical, hippocampal and cerebeller neurons but was
      without detectable effect on dorsal root ganglion neurons and PC12 cells.

PMID- 9917002
TI  - YUA001, a novel aldose reductase inhibitor isolated from alkalophilic
      Corynebacterium sp. YUA25. I. Taxonomy, fermentation, isolation and
      characterization.
AB  - YUA001 is a novel aldose reductase inhibitor produced from alkalophilic
      Corynebacterium sp. YUA25 isolated from soil. YUA001 was purified from the
      supernatant of culture broth by successive silica gel column chromatography,
      Sephadex LH20-100 gel column chromatography, and HPLC. From instrumental
      analysis, molecular formula of YUA001 is C13H19NO2 and its molecular weight is
      221. It exhibits potent aldose reductase inhibition activity and has no
      antimicrobial activity against some gram-positive or gram-negative bacteria,
      fungi and yeast.

PMID- 9917003
TI  - A new antitumor antibiotic, BE-19412A, produced by a streptomycete.
AB  - A new antitumor substance, designated BE-19412A, was isolated from the culture
      broth of Streptomyces sp. A19412. The active principle was extracted from the
      mycelium by methanol and purified by Silica gel and Sephadex LH-20 column
      chromatographies. BE-19412B was prepared by methylation of BE-19412A. BE-19412A
      and B exhibited cytotoxic activity against murine and human tumor cell lines. BE
      19412A prolonged the survival of CDF1 mice bearing i.p. implanted Ehrlich
      carcinoma cells.

PMID- 9917004
TI  - Glucosylquestiomycin, a novel antibiotic from Microbispora sp. TP-A0184:
      fermentation, isolation, structure determination, synthesis and biological
      activities.
AB  - Glucosylquestiomycin, a novel N-glucopyranoside of questiomycin A, was isolated
      from the culture broth of Microbispora sp. TP-A0184. The absolute configuration
      of the sugar was determined as D-configuration by chemical synthesis. The new
      antibiotic showed antibacterial activity against gram-positive and -negative
      bacteria and yeasts and cytotoxic activity against U937 cells.

PMID- 9917005
TI  - 3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces
      sp. HAG 003874.
AB  - New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the
      fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were
      obtained as yellow powders after sequential purification by chromatography on MCI
      Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography. On the basis
      of the results of spectroscopic analysis, it was found that 3874 H1, C58H86N2O18,
      MW 1098, belongs to the p-aminoacetophenone containing family of heptaene
      antibiotics, while 3874 H3, C57H87NO18, MW 1073, is a non-aromatic heptaene. In
      addition to these, a minor component, 3874 H2, C59H88N2O18, MW 1112, a N-methyl
      derivative of 3874 H1 has been detected. The structures were elucidated through
      mass spectral analyses and 1-D and 2-D homonuclear and heteronuclear NMR data.
      The outstanding physico-chemical feature of 3874 H3 is its improved solubility.
      The new heptaenes are potent antifungal compounds with broad activity spectra,
      encompassing dermatophytes, yeasts and filamentous fungi.

PMID- 9917006
TI  - A new anti-MRSA antibiotic complex, WAP-8294A. I. Taxonomy, isolation and
      biological activities.
AB  - WAP-8294A, produced by Lysobacter sp., is a complex consisting of water soluble
      depsipeptide antibiotics. It was further purified by column chromatographies and
      HPLC, and 19 components were obtained. WAP-8294A2, a major component, and minor
      components A1, A4, Ax8, Ax9 and Ax13 were active against gram-positive bacteria,
      in particular, methicillin-resistant Staphylococcus aureus (MRSA) in vitro. WAP
      8294A2 was highly active in vivo in mice against the systemic infection of MRSA.

PMID- 9917008
TI  - Enzymatic deacylation of teicoplanin followed by reductive alkylation: synthesis
      and antibacterial activity of new glycopeptides.
AB  - Novel glycopeptides derived from teicoplanin were prepared and evaluated for
      activity against antibiotic-resistant gram-positive pathogens. Removal of the
      fatty acid sidechains of teicoplanin was accomplished by enzymatic deacylation.
      The resulting deacylated teicoplanin was subjected to reductive alkylation
      resulting in mono- and di-alkylated compounds at the 2 possible primary amines.
      Deacylated teicoplanin was less active than teicoplanin against enterococci and
      staphylococci (MIC > or =32 microg/ml). All mono- and di-alkylated products
      regained some activity, and some had potent activity against both staphylococci
      and glycopeptide-resistant enterococci. MICs of the most potent di-alkylated
      compounds ranged from 0.25 approximately 2 microg/ml against glycopeptide
      resistant enterococci.

PMID- 9917007
TI  - Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction with
      the yeast two-hybrid screening system.
AB  - Activation of cytoplasmic serine/threonine kinase Raf-1, an important effector of
      Ras, requires direct binding to Ras. The yeast two-hybrid screening system used
      for identification of inhibitors of Ras/Raf-1 interaction showed radicicol to be
      an inhibitor. Radicicol has been shown to induce morphological reversion of
      transformed cells. Immunoprecipitation with an anti-Ras antibody revealed that
      the in vivo Ras/Raf-1 binding in v-Ha-ras-transformed cells was also blocked by
      low concentrations of radicicol (0.1 approximately 1 microg/ml), while
      degradation of Raf-1 was induced at concentrations higher than 2 microg/ml.
      However, in vitro binding of glutathion S-transferase-fused Ras to a maltose
      binding protein-fused RIP3 containing the Ras-binding domain (RBD) of Raf-1 was
      not inhibited by radicicol. Similar two-hybrid assays with several truncated
      forms of Raf-1 showed that both the conserved serine/threonine-rich domain (CR2)
      and the C-terminal protein kinase domain (CR3) were required for the full
      inhibition by radicicol. These results suggest that radicicol interacts directly
      or indirectly with the region except with RBD of Raf-1, thereby inhibiting a
      conformational change of Raf-1 prerequisite for binding to Ras.

PMID- 9917009
TI  - GTRI-02, a new lipid peroxidation inhibitor from Micromonospora sp. SA246.

PMID- 9917010
TI  - Sequence analysis of the ribosomal L11 protein gene (rplK=relC) in Streptomyces
      lavendulae using a deletion allele.

PMID- 9917011
TI  - 3-Amino-5-hydroxybenzoic acid in antibiotic biosynthesis. XII. Origin of the
      oxygen functionality of the ansamycin antibiotic actamycin.

PMID- 9917012
TI  - Factumycin and its new derivative RK-1009 enhance threonine-phosphorylation of a
      60-kDa protein in Streptomyces griseus.

PMID- 9917013
TI  - Acremolactone A, a novel herbicidal epoxydihydropyranyl gamma-lactone from
      Acremonium roseum I4267.

PMID- 9917014
TI  - Cost-effectiveness of regulations against using a cellular telephone while
      driving.
AB  - PURPOSE: To evaluate the cost-effectiveness of regulations that prohibit using a
      cellular telephone while driving a motor vehicle. DESIGN: Decision analysis of
      risks and benefits related to cellular telephones and driving. SETTING: United
      States population in 1997. MEASURES: Health benefits measured as the quality
      adjusted life years potentially saved. Financial benefits measured as health care
      and other services potentially averted. Costs of regulation measured as the lost
      productivity derived from willingness to pay for cellular telephone calls.
      RESULTS: Under base-case conditions, cellular telephone calls in the United
      States each day accounted for about 984 reported collisions, 1,729 total
      collisions, 2 deaths, 317 persons with injuries, 99 lost years of life
      expectancy, 161 lost quality-adjusted life years, $1 million in health care
      costs, and $4 million in property damage and other costs. This reflected a total
      of about 35 million telephone calls while driving, 70 million calling minutes,
      and $33 million in total value to society. The estimated cost-effectiveness ratio
      for a regulation restricting cellular telephone usage while driving was $300,000
      per quality-adjusted life year saved, but ranged from $50,000 to $700,000 under
      alternative assumptions and interpretations of data. Regulations applied to
      teenage males could be cost-saving to society if the value of a call fell below
      37 cents per minute. CONCLUSIONS: Regulations restricting cellular telephone
      usage while driving are less cost-effective for society than other safety
      measures. Nevertheless, regulations may be justifiable because the benefits and
      harms do not always involve the individual who has the cellular telephone.
      Increasing the price of a call (or adding a supplementary tax) might decrease the
      number of discretionary calls, be cost-saving for society, and be life-saving for
      individuals.

PMID- 9917015
TI  - Problems with interval estimates of the incremental cost-effectiveness ratio.
AB  - The defining feature of a confidence interval is that it has a fixed minimum
      probability of covering the true value of the parameter being estimated, whatever
      the value of the parameter. The authors demonstrate by simulation that some
      recently proposed methods for interval estimation of the incremental cost
      effectiveness ratio (ICER) either do not satisfy this definition or have other
      problems that limit their usefulness in applications. The problems are most
      prominent when the ICER is large and the true effectiveness difference is small
      relative to its standard error. A modification of the percentile bootstrap
      confidence interval that involves a reordering of the sample space provides a
      partial solution of the problem.

PMID- 9917016
TI  - The stability of preferences for life-sustaining care among persons with AIDS in
      the Boston Health Study.
AB  - BACKGROUND: Clinicians recognize the importance of eliciting patient preferences
      for life-sustaining care, yet little is known about the stability of those
      preferences for patients with serious disease. OBJECTIVES: To examine the
      stability of preferences for life-sustaining care among persons with AIDS and to
      assess factors associated with changes in preferences. DESIGN: Two patient
      surveys and medical record reviews, administered four months apart in 1990-1991.
      SETTING: Three health care settings in Boston. PATIENTS: 252 of 505 eligible
      persons with AIDS who participated in both baseline and follow-up surveys. MAIN
      OUTCOME MEASURES: A single question assessing desire for cardiac resuscitation
      and a scale of preferences for life-extending treatment conditional on
      hypothetical health states. RESULTS: Approximately one-fourth of the respondents
      changed their minds about life-sustaining care during a four-month period. Of
      patients who initially desired cardiac resuscitation, 23% decided to forego it
      four months later, and of those who initially said they would decline care, 34%
      later said they would accept it. Of those who initially desired any of the life
      extending treatments, 25% decided to forego them four months later, and of those
      who initially said they would decline life-extending care, 24% later said they
      would accept some treatment. Patients reporting changes in physical function,
      pain, or suicide ideation were more likely to modify their desires to be
      resuscitated (all p< or =0.05). Patients lacking an advance directive, not
      completing high school, or becoming more severely ill were more likely to change
      their preferences on the Life Extension scale (p< or =0.05). Patients who
      discussed their preferences with at least one physician were just as likely as
      others to change desires for cardiac resuscitation. Age, gender, race, emotional
      health, clinical severity, social support, and site of care were not significant
      correlates of change for either measure. CONCLUSIONS: Health care providers
      should periodically reassess preferences for life-sustaining care, particularly
      for patients with progressive disease, given the instability in patient
      preferences. However, predictors of instability may vary with how preferences are
      measured. In particular, changes in health status may be related to instability
      of preferences for certain types of treatments.

PMID- 9917017
TI  - Measuring patient preferences by willingness to pay to avoid: the case of acute
      otitis media.
AB  - The aim of this study was to evaluate willingness to pay (WTP) to avoid as a
      method of eliciting relative values for use in expected-value (EV) decision
      making. Parents' preferences for the events and outcomes associated with acute
      otitis media (AOM) and its treatment were quantified by means of a questionnaire
      asking how much they would be willing to pay to avoid them. Their responses were
      then used to calculate the EVs of treating or not treating presumed AOM with
      antibiotics. The advantages of the WTP method were its simplicity, its analogy
      with everyday financial transactions, its explicit recognition of illness and its
      management as involving decreases in value, and its face validity. The
      disadvantages included the need to use another method (the standard gamble) to
      derive a value for death and the wide ranges and the poor test-retest reliability
      of individual parents' responses. Nonetheless, median WTP values and their ranges
      may prove useful in defining for physicians and policymakers the parameters of
      their practical management decisions. In the case of AOM, the EV of treating with
      antibiotics was, for the aggregate sample and for most individual parents,
      robustly superior because of parents' desire to avoid any increased risk of their
      children's death.

PMID- 9917018
TI  - A method for evaluating health care providers' decision making: the Provider
      Decision Process Assessment Instrument.
AB  - Valid and reliable assessment of the clinical decision-making process is
      essential for the evaluation of decision aiding methods and effective quality
      assurance programs. The Provider Decision Process Assessment Instrument is a 12
      item questionnaire that measures a health care provider's degree of comfort with
      a medical decision. Its measurement properties were studied in two general
      internal medicine practices. Reliability, measured using Cronbach's alpha, was
      0.90 (95% Cl = 0.87 to 0.92). Construct validity was also high, with expected
      negative correlations ranging from -0.53 to -0.67. The instrument also satisfied
      standard criteria for item homogeneity and was readily completed by clinicians.
      These results suggest that the Provider Decision Process Assessment Instrument
      will prove to be a valuable tool for assessing medical decision making in busy
      clinical settings.

PMID- 9917019
TI  - A practice pathway for the initial diagnostic evaluation of isolated sixth
      cranial nerve palsies.
AB  - PURPOSE: To define a practice pathway for the evaluation of sixth-nerve palsies
      (SNPs) and to determine its cost-effectiveness and validity in a retrospective
      chart review. METHODS: A Medline search of the English-language literature from
      1966 to 1995 was performed to define the available clinical evidence and develop
      the practice pathway. The authors retrospectively reviewed 407 charts with the
      diagnosis of SNP seen at three centers. Information obtained included: etiologic
      diagnosis if known; development of new neurologic or ophthalmologic findings; and
      results and costs of neuroimaging studies, if performed. RESULTS: Of the 407
      patients, 98 underwent computed tomography scans and 212 underwent magnetic
      resonance imaging of the head. Eighty cases were non-isolated, 317 were isolated
      SNP, and ten could not be classified from chart information. Of the 317 cases of
      isolated SNP, 49 were classified as traumatic; 5, congenital; 158, vasculopathic;
      63, nonvasculopathic; and 42, progressive or unresolved. Following the
      recommendations of the practice pathway, the 158 patients classified as having
      vasculopathic SNP would not have undergone neuroimaging studies, realizing a
      savings of $100,000 in this study population of 407 patients. CONCLUSION: The
      recommendations of the practice pathway are supported by review of the literature
      and the retrospective review of these cases. However, a prospective study with a
      matched control group is needed to demonstrate regional and specialty-specific
      variations in care and to strengthen the clinical certainty of the pathway
      recommendations.

PMID- 9917020
TI  - Analysis of three decision-making methods: a breast cancer patient as a model.
AB  - PURPOSE: To compare three decision making techniques using a common clinical
      problem. METHODS: Two recently developed methods, the analytic hierarchy process
      (AHP) and the analytic network process (ANP), were compared with a Markov process
      in the evaluation of the optimal post-lumpectomy treatment strategy for an
      elderly woman with a mammographically detected, nonpalpable early-stage breast
      cancer. The following treatment alternatives were considered: observation,
      radiation, tamoxifen, combination radiation and tamoxifen, and simple mastectomy.
      All three decision methods incorporated patient preferences. RESULTS: The models
      agreed on the ranking of the preferred treatment, radiation and tamoxifen, but
      there were variations in the rankings of the other treatment choices. Individual
      differences between the three models were uncovered. The Markov process provided
      estimates of quality-adjusted life expectancy and distribution of health events.
      Both AHP and ANP required less development time than the Markov process.
      CONCLUSION: All three methods may be useful tools to the clinician in analyzing
      complex medical problems. The Markov is the most labor-intensive method but
      provides detailed results, whereas the AHP and the ANP give only rank orders of
      the alternatives. The most important considerations in choosing between these
      methods are time to project completion and the detail of information sought.

PMID- 9917021
TI  - Multiattribute utility scores for predicting family physicians' decisions
      regarding sinusitis.
AB  - To examine whether multiattribute utility (MAU) scores can be used to predict
      family physicians' decisions regarding patients suspected to have sinusitis and
      rhinitis, 100 randomly selected family physicians from the Leiden area (The
      Netherlands) were asked to rank a set of six attributes regarding their
      importance, yielding attribute weights. Next, the physicians were asked to rate
      the degrees to which five decision alternatives optimized each attribute,
      yielding utilities, regarding three case vignettes about a patient suspected to
      have acute maxillary sinusitis and rhinitis, with a brief clinical history. By
      combining attribute weights and utilities, a MAU score was calculated for each
      decision alternative regarding each case vignette. Finally, for each case
      vignette the physicians' treatment preferences were assessed by means of an open
      ended question. For the clear-cut sinusitis case, management strategies and
      highest MAU scores were concordant for 80% of the physicians. Regarding the
      dubious sinusitis and rhinitis case, concordance was 50%. The latter was
      associated with small differences in values between the highest MAU scores.
      Because agreement among the physicians regarding the management strategies and
      weight ranks was high and there was little variation in the highest MAU scores,
      the kappas between the reported management strategies and weight ranks were poor
      (0.24 and lower). It is concluded that MAU scores may be used to predict family
      physicians' decisions regarding the management of patients suspected of having
      sinusitis where there are significant differences in values between the highest
      MAU scores.

PMID- 9917022
TI  - Patient or physician preferences for decision analysis: the prenatal genetic
      testing decision.
AB  - The choice between amniocentesis and chorionic villus sampling for prenatal
      genetic testing involves tradeoffs of the benefits and risks of the tests.
      Decision analysis is a method of explicitly weighing such tradeoffs. The authors
      examined the relationship between prenatal test choices made by patients and the
      choices prescribed by decision-analytic models based on their preferences, and
      separate models based on the preferences of their physicians. Preferences were
      assessed using written scenarios describing prenatal testing outcomes, and were
      recorded on linear rating scales. After adjustment for sociodemographic and
      obstetric confounders, test choice was significantly associated with the choice
      of decision models based on patient preferences (odds ratio 4.44; Cl, 2.53 to
      7.78), but not with the choice of models based on the preferences of the
      physicians (odds ratio 1.60; Cl, 0.79 to 3.26). Agreement between decision
      analyses based on patient preferences and on physician preferences was little
      better than chance (kappa = 0.085+/-0.063). These results were robust both to
      changes in the decision-analytic probabilities and to changes in the model
      structure itself to simulate non-expected utility decision rules. The authors
      conclude that patient but not physician preferences, incorporated in decision
      models, correspond to the choice of amniocentesis or chorionic villus sampling
      made by the patient. Nevertheless, because patient preferences were assessed
      after referral for genetic testing, prospective preference-assessment studies
      will be necessary to confirm this association.

PMID- 9917023
TI  - Three-way ROCs.
AB  - Receiver operating characteristic (ROC) analysis traditionally has dealt with
      dichotomous diagnostic tasks (e.g., determining whether a disorder is present or
      absent). Often, however, medical problems involve distinguishing among more than
      two diagnostic alternatives. This article extends ROC concepts to diagnostic
      enterprises with three possible outcomes. For a trichotomous decision task, one
      can plot a ROC surface on three-dimensional coordinates; the volume under the ROC
      surface (VUS) equals the probability that test values will allow a decision maker
      to correctly sort a trio of items containing a randomly-selected member from each
      of three populations. Thus, the VUS summarizes global diagnostic accuracy for
      trichotomous tests, just as the area under a ROC curve does for a two-alternative
      diagnostic task. Information gain at points on the surface can be calculated just
      as is done for two-dimensional ROC curves, and investigators can thus compare
      three-way ROCs by comparing maximum information gain on each ROC surface.

PMID- 9917024
TI  - Computing population-based estimates of health-adjusted life expectancy.
AB  - Observed health-adjusted life expectancy (HALE) is an indicator of population
      health. There are a number of ways to compute HALE for a community. The authors
      surveyed several methods and demonstrate resulting variation in the estimates of
      HALE. Quality of well-being (QWB) measures from 1,430 participants in the Beaver
      Dam Health Outcomes Study are taken as weights. Actuarial life-table methods
      using community mortality data, State of Wisconsin census data from two time
      frames, and U.S. census data are used with the QWB to estimate HALE. Measurement
      of community population health using HALE computations can be completed with
      national, regional, or local data. Community-level estimates may not be well
      approximated using large-scale mortality experience. A Bayesian method is
      developed combining the local data with regional data. The Bayesian method
      creates a smooth set of rates, retains the local flavor of the community, and
      gives a measure of variability of the estimated HALE.

PMID- 9917025
TI  - What is the government's perspective?

PMID- 9917026
TI  - Government and society: yet another perspective.

PMID- 9917027
TI  - Calling while driving: laws, economics, and commandments.

PMID- 9917028
TI  - Is it really so bad to be unambiguously inefficient? The role of dominance in
      stochastic cost-effectiveness analysis.

PMID- 9917029
TI  - Law and ethics. Law and sociology of knowledge (court-compelled disclosure of
      research data).

PMID- 9917030
TI  - "Babe" Ruth's illness and its impact on medical history.

PMID- 9917031
TI  - Management of the N0 neck during salvage laryngectomy.
AB  - BACKGROUND: Radiotherapy is effective treatment for laryngeal carcinoma. Early
      stage laryngeal carcinoma has a low incidence of cervical metastasis. Patients
      initially clinically N0 usually remain N0 when they fail at the primary site. The
      incidence of subclinical metastasis in these patients is not well described.
      Watchful waiting or elective neck dissections are advocated. OBJECTIVE: Examine
      the incidence of subclinical metastatic disease in patients undergoing elective
      neck dissections with salvage laryngectomy. STUDY DESIGN: Prospective study (1991
      1996) of patients who failed radiotherapy and underwent salvage laryngectomy with
      elective neck dissection. METHODS: Thirty-four patients underwent salvage
      laryngectomy with neck dissection (30 bilateral, 4 unilateral). All were
      clinically N0 at initial presentation and remained N0 at recurrence. Pathologic
      study of the neck dissection specimens was undertaken. Patients were followed for
      a minimum of 2 years (mean, 4 y). RESULTS: The male-to-female ratio was 4.5:1,
      with a mean age of 62 years (range, 38 to 75 y). Metastatic disease was present
      in 6 patients (17%); 4 of 14 (28%) supraglottic, and 2 of 20 (10%) glottic.
      Presence of disease in the neck according to stage at recurrence was as follows:
      T2, 2 of 12; T3, 3 of 14; and T4, 2 of 8. Neck disease was ipsilateral in 4 and
      contralateral in 2 patients (both supraglottic primaries). CONCLUSIONS:
      Subclinical cervical metastasis may be present in N0 laryngeal carcinoma patients
      who have recurrence following radiotherapy. Morbidity of a lateral neck
      dissection is minimal, with excellent control of the neck being possible.
      Supraglottic and advanced glottic (T3-T4) patients may benefit the most.

PMID- 9917032
TI  - Effect of internal maxillary arterial occlusion on nasal blood flow in swine.
AB  - OBJECTIVES: The precise effects of therapeutic occlusion of the internal
      maxillary artery (IMA) on distal nasal mucosal perfusion are unknown. A better
      understanding of these effects has important implications regarding the rationale
      and expected efficacy of certain therapeutic interventions for epistaxis
      management. The authors developed an animal model to assess these issues. STUDY
      DESIGN: The effects of "proximal" and progressively more "distal" occlusions of
      the IMA on nasal mucosal blood flow (NBF) were assessed in anesthetized swine
      using continuous laser Doppler flowmetry. The levels of arterial occlusion were
      selected to simulate clinical therapeutic occlusions used for the management of
      epistaxis. METHODS: Nineteen swine were entered into one of four experimental
      groupings: proximal IMA occlusion using platinum micro-coils (n = 6), mid-grade
      distal IMA occlusion with polyvinyl alcohol particulate (PVA) suspensions (300 to
      500 microns, n = 5), high-grade distal IMA occlusion with polyvinyl alcohol
      particulate suspensions (50 to 150 microns, n = 5), and sham control (n = 2).
      RESULTS: All embolizations resulted in acute decreases in average NBF from 120
      mL/min per 100 g to 40 mL/min per 100 g (P < .05 for all groups). NBF returned to
      baseline in all three treated groups within 2 to 8 days after therapeutic
      embolization, depending on the level of occlusion (coils, 2 d; mid-grade PVA, 2-3
      d; high-grade PVA, 8 d). Follow-up angiography showed recanalization and
      collateralization as possible methods of reestablishing NBF. CONCLUSIONS: This
      study supports the rationale for performing distal IMA occlusion with
      transarterial particulate embolization, in order to provide a longer period of
      time of diminished NBF. This theoretically should promote hemostasis within an
      injured portion of the nasal mucosa by decreasing perfusion pressure within the
      capillary bed. However, the benefits of distal IMA embolization must be balanced
      against potential ischemic complications, as may be more commonly seen with high
      grade particulate embolization.

PMID- 9917033
TI  - Argon plasma coagulation for the treatment of hereditary hemorrhagic
      telangiectasia.
AB  - OBJECTIVES: Patients with (HHT) often suffer from recurrent epistaxis, which
      poses considerable therapeutic problems. Theoretical considerations render argon
      plasma coagulation (APC) a promising new therapeutic approach. STUDY DESIGN: In a
      prospective study 12 patients (aged 8-68 y) who presented with a long history of
      treatment for epistaxis were treated with telangiectasia in the nasal mucosa.
      After 2 weeks and again after 4 months the treatment results were evaluated by
      questionnaire. METHODS: APC is based on high-frequency electric energy
      transmitted through ionized argon gas to the tissue in a noncontact mode.
      Coagulation and desiccation of tissue are limited to 1 to 2 mm of penetration and
      therefore risk of tissue damage is low. Coagulative effects are best in tissue
      with high electrical conductivity, especially blood vessels. RESULTS: All
      patients were satisfied with the postoperative results. Frequency and intensity
      of bleeding were significantly reduced. All patients reported better
      postoperative results than with any other treatment they had received previously.
      CONCLUSION: First clinical experience shows that APC is a useful alternative for
      the treatment of telangiectasia in the nasal mucosa and should be a therapeutic
      option for this disease.

PMID- 9917034
TI  - Relationship of human papillomavirus to Schneiderian papillomas.
AB  - OBJECTIVES/HYPOTHESIS: To classify a large group of Schneiderian papillomas (SPs)
      into their histologic subtypes and to determine the incidence of human
      papillomavirus (HPV) in each subtype. STUDY DESIGN: Pathologic review and
      polymerase chain reaction-based (PCR-based) examination of archived tissue.
      METHODS: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or
      cylindric cell papillomas, or any associated carcinomas, were examined by a head
      and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were
      used to determine the presence of HPV in the tumors. This was also performed on
      normal turbinate control specimens. RESULTS: Eighty-two (78%) were the inverting
      subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine
      tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty
      eight percent of the tumors had DNA of sufficient quality to be amplified using
      PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2
      cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was
      positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11
      accounted for all cases of fungiform papillomas. Of the five HPV-positive
      inverting papillomas, three had HPV type 11 and two had HPV type 16. The single
      carcinoma containing HPV contained HPV type 18. CONCLUSIONS: The histologic
      subtype of SPs is important, as their etiologies appear to be different. HPV 6b
      and 11 appear to be involved in all cases of fungiform papillomas but are only
      rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may
      rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be
      involved in a subset of cases of carcinomas originating in an inverting
      papilloma.

PMID- 9917035
TI  - Surgical causes of failure in endoscopic sinus surgery.
AB  - OBJECTIVES: Evaluate causes of surgical failure at time of revision endoscopic
      sinus surgery. STUDY DESIGN: Prospective review of 682 cases that had endoscopic
      sinus surgery performed between 1991 and 1995. METHODS: In all cases, variables
      of age, sex, asthma, allergy, computed tomography stage, associated procedures,
      complications, and operative findings were collected. Those cases that had a
      failure after a previous endoscopic sinus procedure and not an intranasal
      procedure or an external procedure were evaluated. RESULTS: Fifty-two patients
      (7.6%) were identified. The age range was 24 to 70 years. The most common cause
      of failure was residual air cells and adhesions in the ethmoid area (30.7%),
      followed by maxillary sinus ostium stenosis in 27%, frontal sinus ostium stenosis
      in 25%, and a separate maxillary sinus ostium stenosis in 15% of the cases.
      CONCLUSION: Review of surgical causes of failure in endoscopic sinus surgery
      patients revealed that residual air cells and stenotic maxillary or frontal sinus
      ostium were the most common causes of failures.

PMID- 9917036
TI  - Malignant glomus tumors.
AB  - OBJECTIVES/HYPOTHESIS: To ascertain the incidence of malignancy in a large glomus
      and skull base series and to compare the clinical course of such patients with
      those who do not have malignant skull base lesions. STUDY DESIGN: Retrospective
      review of all skull base surgery cases treated at the Otology Group between 1970
      and 1995. RESULTS: In a series of 175 jugulotympanic glomus tumors, 9 cases
      (5.1%) were identified. The surgery required for their extirpation is more
      extensive than nonmalignant glomus tumors. Attendant deficits and mortality from
      these procedures are accordingly greater. Five-year survival in this limited
      population was 72%. Prolonged periods of survival are possible with distant
      metastases. CONCLUSIONS: This rate of malignancy should advocate against a
      watchful, waiting approach. Radiation therapy is not advocated as a primary
      modality for this type of tumor, as it may lead to recurrence/persistence with
      either subsequent malignant degeneration and metastases or local recurrence.

PMID- 9917037
TI  - Prognosis in bilateral vestibular hypofunction.
AB  - OBJECTIVES/HYPOTHESES: The outcomes of patients with bilateral vestibular
      hypofunction vary widely. Some resume relatively normal activity within months,
      whereas others have a more debilitated course. This study sought to identify
      factors that may affect outcome. STUDY DESIGN: A retrospective review of patients
      treated for bilateral vestibular hypofunction over a 2-year period at a
      neurotology clinic. METHODS: Patients' medical charts, electronystagmography
      data, rotatory chair testing, and posturography results were reviewed. Subjective
      and objective measures were used to evaluate outcome. RESULTS: Bilateral
      vestibular hypofunction was diagnosed in 35 patients. Improvement after
      vestibular rehabilitation therapy was noted in 18 patients (51%), whereas 12
      (34%) showed little or no change and 5 (15%) were not available for follow-up.
      The patients without improvement were more likely to have a chronic disorder as a
      cause of the vestibulopathy and had more medical comorbidities, on average, when
      compared with those who improved. Lower gains and time constants on rotatory
      chair testing were also seen in the group that did not improve. CONCLUSIONS: Poor
      rehabilitation results may be attributable to increased severity of vestibular
      insult, progressive peripheral or central vestibular dysfunction, and multiple
      medical problems.

PMID- 9917038
TI  - Quality of life assessment in patients undergoing head and neck surgery as
      evaluated by lay caregivers.
AB  - OBJECTIVES/HYPOTHESIS: Rehabilitation following head and neck cancer surgery has
      steadily moved into the outpatient realm and become dependent on caregivers with
      no formal medical background (lay caregivers.) Satisfactory rehabilitation and
      quality of life (QOL) depend on successful relationships between patients and the
      lay caregivers. This study evaluates the QOL assessments of patients by
      themselves and their primary lay caregivers before head and neck surgery. STUDY
      DESIGN: Institutional Review Board-approved study using validated QOL assessment
      instrument. MATERIALS AND METHODS: The preoperative QOL status in 50 patients
      undergoing extensive head and neck surgery was evaluated using the self
      administered Medical Outcomes Survey Short Form 36 (SF-36). The patient's primary
      lay caregiver (spouse, child, or friend) completed a similar questionnaire
      evaluating the patient's status. RESULTS: Thirty-three (66%) questionnaires were
      returned. Twenty-five (50%) questionnaire sets were successfully completed by
      both parties and employable for comparison. Sixty percent of the caregivers were
      within the 90% confidence interval of the patient's assessment for six or more of
      the eight parameters evaluated by the SF-36. Likewise, caregiver assessments for
      specific parameters were consistently congruent with patient evaluation, except
      for the parameters of bodily pain and general health, for which caregivers
      demonstrated a trend for overrating pain and underestimating general health.
      Caregivers of the same generation as the patient demonstrated significantly
      higher congruence (P = .007). Similarly, a trend for higher congruence was noted
      in patients with recurrent disease. CONCLUSIONS: The importance of the lay
      caregiver has increased in the era of greater outpatient rehabilitation. This
      pilot study indicates that QOL assessment by lay caregivers may be examined with
      existing instruments and highlights QOL parameters critical to both the head and
      neck surgery patient and his or her primary lay caregiver.

PMID- 9917039
TI  - Myringoplasty in children: predictive factors of outcome.
AB  - OBJECTIVES: To assess the results of myringoplasty in children and to determine
      which factors independently influence the postoperative results. STUDY DESIGN:
      Retrospective study of the anatomic and functional results of 231 consecutive
      myringoplasties performed in 188 children between 1988 and 1992. Multivariate
      analysis of poor prognostic factors by cross-sectional comparison 1 year after
      surgery. METHODS: Myringoplasties were performed via an endaural approach with a
      fascia temporalis underlay graft. RESULTS: In 216 of 231 ears (93.5%) the
      tympanic membrane was closed. A good anatomic outcome was considered to have been
      achieved in 188 ears (81.6%), although in 18 ears (7.8%) seromucous otitis media
      occurred, in 8 ears (3.5%) a progressive retraction pocket was encountered, and
      in 2 ears significant lateralization was present. One hundred thirty-nine (67.5%)
      of the 206 ears tested in the postoperative period had a postoperative air-bone
      gap of 10 dB or less. On average, mean bone conduction remained unaltered. The
      age of the patient and the size and the location of the perforation did not
      affect the outcome. Three prognostic factors for an abnormal postoperative
      tympanic membrane were found, with 95% confidence intervals: inflammatory changes
      in the middle ear mucosa (P < .05), contralateral tympanic perforation (P < .05),
      and contralateral cholesteatoma (P < .01). CONCLUSIONS: Myringoplasty with
      underlay grafting of the fascia temporalis in children gives good anatomic and
      functional results. Inflammatory changes within the middle ear mucosa,
      contralateral tympanic perforation, and contralateral cholesteatoma independently
      influence the risk of an abnormal postoperative tympanic membrane. The presence
      of one of these factors preoperatively should lead to the consideration of
      alternative, more durable graft material, such as autologous cartilage.

PMID- 9917040
TI  - Stapes surgery in a residency training program.
AB  - OBJECTIVES: Determine parameters for successful stapedectomy and whether this
      procedure can be performed safely by residents in a teaching hospital. STUDY
      DESIGN: Retrospective analysis of techniques and results for 71 stapedectomy
      procedures. MATERIALS AND METHODS: Charts were reviewed for technique,
      audiological test results, complications, operative time, and anesthetic used.
      RESULTS: Overall, closure of the air-bone gap at 10 dB was achieved in 87% of
      patients. Use of general anesthesia and a laser-assisted, small-fenestra
      technique allowed residents to complete more operations. No severe sensorineural
      hearing loss was noted. CONCLUSIONS: Residents can safely and successfully
      perform stapes surgery using a laser-assisted, small-fenestra technique.

PMID- 9917041
TI  - Transverse/sigmoid sinus dural arteriovenous fistulas presenting as pulsatile
      tinnitus.
AB  - OBJECTIVE/HYPOTHESIS: Transverse/sigmoid sinus dural arteriovenous fistula
      (TSDAVF) is a diagnostically elusive entity that is critical for the otologist to
      account for, when confronted by pulsatile tinnitus in the face of normal
      otoscopy. Left untreated, TSDAVF may result in catastrophic outcome. We have
      previously proposed a grading system specifically for TSDAVF based on venous
      restrictive disease. Our objective was to assess the validity of this grading
      system for clinical severity and therapeutic outcome. METHODS: Through a
      retrospective review of 41 patients with TSDAVF, we evaluated clinical
      presentation, diagnostic evaluation, therapy, and outcome. Patients were
      classified into four grades based on the severity of venous restrictive disease
      as determined by superselective angiography. Our treatment algorithm combined
      compression therapy, transarterial embolization, and for more severe grades,
      surgery. RESULTS: Pulsatile tinnitus was the chief complaint of all the patients
      in this series, and of 90% of all cases of TSDAVF treated at our institution.
      While angiography remains the gold standard, magnetic resonance imaging/magnetic
      resonance arteriography is far superior to computed tomography scanning in
      detecting dural arteriovenous fistulas. As normal venous outflow gives way to
      aberrant cortical venous drainage in higher grades, there is a dramatically
      increased risk for adverse consequences with therapeutic intervention. Using our
      treatment algorithm, 82% of patients achieved clinical resolution of symptoms.
      Half of these patients had complete angiographic obliteration of their TSDAVF.
      CONCLUSIONS: The TSDAVF-specific grading system for the severity of venous
      restrictive disease is reflective of clinical presentation, fundamental in
      planning treatment, and predictive of therapeutic outcome.

PMID- 9917042
TI  - Electrocochleographic and audiometric evaluation of hypobaric effect in Meniere's
      disease.
AB  - OBJECTIVES: To elucidate the effects of hypobaric pressure on cochlear
      hydrodynamics in patents with well-defined Meniere's disease. DESIGN: Sixteen
      patients were consecutively selected. Elevated hearing threshold levels and
      pathological transtympanal electrocochleography (tt-ECOG) were confirmed at the
      day of trial. The patients were exposed to repeated episodes of hypobaric
      pressure in a pressure chamber. The rate (20 daPa/s) and magnitude (-285 daPa) of
      chamber pressure change were low. The induced tympanic overpressure (+185 daPa)
      was continuously monitored and any tympanic equilibration was avoided. METHODS:
      The results of Bekesy and speech audiometry as well as tt-ECOG performed
      immediately before and after exposure were compared. The importance of chamber
      pressure change, number of hypobaric episodes, duration of exposure, and the
      induced relative tympanic overpressure was tested. RESULTS: It is shown that the
      relative tympanic overpressure is the most important factor to affect the
      cochlear hydrodynamics. Higher relative overpressure was associated with
      improvement of hearing threshold levels, while the ECOG results tended to improve
      with lower induced tympanic overpressure. CONCLUSION: The importance of tympanic
      overpressure shown in this study is in agreement with previous findings from
      hypobaric animal experiments. The inverse relation of psychoacoustic and ECOG
      tests suggests that the two methods evaluate different parameters, perhaps
      contributing differently to the physiology of hearing.

PMID- 9917043
TI  - Radiologic and mechanical properties of inactivated ossicle homografts.
AB  - OBJECTIVE: This study examined the effects of old and new inactivation
      (sterilization) techniques on the radiologic and mechanical properties of ossicle
      homografts. MATERIALS AND METHODS: Ninety normal incuses and malleuses received
      either treatment with 1) 5% formaldehyde/cialit, 2) 1N NaOH, 3) 0.9% LpH, or 4)
      autoclaving at 134'C, or no treatment. All ossicles were assessed radiologically
      by high-resolution computed tomography. After imaging, all ossicles underwent
      mechanical testing by destructive axial compression in a mechanical testing
      machine measuring force and displacement. RESULTS: Ossicles treated with cialit,
      NaOH, or autoclaving showed a significant decrease of ultimate force and
      stiffness compared with controls. LpH treatment caused no such changes in these
      structural properties. Material properties of yield strength, ultimate strength,
      and elastic modulus were also altered by cialit, NaOH, and autoclaving, but were
      much more difficult to assess because of uncertainty in parameter estimates.
      There was a significant increase in radiologic density in autoclaved ossicles, a
      reduction in cialit- and LpH-treated ossicles, and no change in NaOH-treated
      ossicles. CONCLUSIONS: All tested inactivation procedures changed the
      biomechanical and/or radiologic properties of ossicle homografts. However, the
      new procedures used to inactivate infectious agents produced changes similar to
      the older treatments with formaldehyde/cialit. Human allografts are able to
      withstand harsh but safe sterilization procedures. The NaOH treatment seems to be
      the most suitable method for the future. The biologic (osteogenic) potentials of
      ossicle homografts treated with these new preservation/inactivation methods are
      still unknown. Further investigations are necessary to re-evaluate the clinical
      use of ossicle homografts in middle ear reconstructive surgery.

PMID- 9917044
TI  - A model to explain the rapid pressure decrease after air-inflation of diseased
      middle ears.
AB  - OBJECTIVES: Air-inflation in humans and monkeys with significant negative middle
      ear pressure or with middle ear inflammation was shown to cause greater than
      ambient middle ear pressure initially, followed by a rapid rate of pressure
      decrease to approach the preinflation value. STUDY DESIGN: A mathematical model
      of middle ear pressure regulation is presented and used to simulate air-inflation
      of the normal and diseased middle ear. MATERIALS AND METHODS: The model
      represents the total volume of the middle ear as consisting of three
      subcompartments representing the airspace, effusion, and mucosa/blood. Gas
      exchange among those compartments was assumed to be diffusion limited, and the
      gas exchange between the mucosa/blood compartment and systemic blood was assumed
      to be perfusion limited. Disease was modeled as an increase in mucosal blood flow
      or, alternatively, as an increase in the volumes of the effusion and mucosa/blood
      compartments. RESULTS: The predictions of the model agree better with the
      experimental data when the increased rate of pressure change after middle ear
      inflation in diseased ears is driven by an increased volume of the effusion
      compartment as opposed to an increased perfusion rate. The responsible mechanism
      is a rapid redistribution among subcompartments of the gas volume introduced into
      the air compartment. CONCLUSIONS: These results suggest that middle ear inflation
      with inert gas can be used to diagnose the presence and relative amount of middle
      ear effusion, and that current protocols for treating otitis media with effusion
      using inflation need to be modified to optimize their intended effect.

PMID- 9917045
TI  - Laser-assisted uvulopalatoplasty for the treatment of mild, moderate, and severe
      obstructive sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: Until recently, laser-assisted uvulopalatoplasty (LAUP)
      has been used to treat only snoring and mild cases of obstructive sleep apnea
      (OSA). The purpose of this study was to evaluate the efficacy and safety of LAUP
      in patients with mild, moderate, and severe OSA. STUDY DESIGN: A prospective
      study of 38 patients who completed LAUP for the treatment of OSA who were
      evaluated based on the severity level of their preoperative apnea. MATERIALS AND
      METHODS: Between July 1993 and December 1995, 96 patients with a diagnosis of OSA
      based on polysomnography underwent staged outpatient LAUP treatment. Thirty-eight
      patients completed treatment and obtained postoperative polysomnography.
      Postoperative complications and polysomnographic findings were reviewed. RESULTS:
      Fifteen patients had a diagnosis of mild apnea, 12 had moderate apnea, and 11 had
      severe apnea based on preoperative polysomnography. The surgical response rates,
      defined as greater than or equal to 50% reduction in the postoperative
      respiratory disturbance index (RDI) and a postoperative RDI of less than 20, were
      46.7% in the mild apneics, 41.7% in the moderate apneics, and 45.5% in the severe
      apneics. Postoperative complications in this series included minor bleeding, oral
      candidiasis, and temporary velopharyngeal insufficiency. There were no serious
      complications. CONCLUSIONS: In the carefully selected and prepared patient with
      mild, moderate, or severe OSA, LAUP should be considered a surgical option for
      the treatment of this disorder. LAUP remains a cost-effective and safe
      alternative to uvulopalatopharyngoplasty.

PMID- 9917046
TI  - Persisting dysphagia after uvulopalatoplasty performed with steel scalpel.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the present study was to determine the
      incidence of postoperative persisting dysphagia after uvulopalatoplasty performed
      with conventional steel scalpel (UPP) and to videoradiographically evaluate the
      oral and pharyngeal phases of swallowing in patients reporting persisting
      dysphagia. The hypothesis to be tested was that patients treated with UPP would
      demonstrate a lower incidence of persisting dysphagia than previously found after
      uvulopalatoplasty performed with laser technique (LUPP). STUDY DESIGN:
      Retrospective. METHODS: Sixty-eight of 76 consecutive patients treated with UPP
      answered a questionnaire concerning outcome and late complications after the
      operation. The patients who reported postoperative dysphagia were additionally
      interviewed at a minimum of 1 year postoperatively, and the oral and pharyngeal
      phases of swallowing were videoradiographically examined in those with persisting
      dysphagia. RESULTS: The incidence of persisting dysphagia after UPP was 29%.
      Videoradiographically 71% of the dysphagic patients showed a deviant pharyngeal
      swallowing pattern. CONCLUSION: The incidence of persisting dysphagia after UPP
      did not differ from that reported after laser uvulopalatoplasty. Dysphagia after
      UPP was mostly associated with videoradiographic signs of deviant pharyngeal
      swallowing function. Patients should be informed that there is a risk of
      developing dysphagia after uvulopalatoplasty.

PMID- 9917047
TI  - Effect of steroids on nasal inflammatory cells and cytokine profile.
AB  - OBJECTIVES: To assess the cellular and humoral effects of unilateral topical
      steroid application on the nasal mucosa of chronic sinusitis patients. STUDY
      DESIGN: Cohort study with randomized grouping. METHODS: Chronic sinusitis
      patients awaiting endonasal sinus surgery were randomly divided into a study
      group and a control group. All patients underwent allergy studies and categorized
      as allergic or nonallergic. Patients in the study group were exposed unilaterally
      to fluticasone propionate nasal spray, 100 microg/day for 4 to 6 weeks before the
      planned surgery. The control group was not exposed to steroids. At the time of
      surgery, anterior ethmoid mucosa specimens were obtained. The samples were
      immunostained for CD3, MBP, CD68, elastase, and tryptase. In situ hybridization
      was used for the detection of interleukin (IL)-4, IL-5, and interferon gamma (IFN
      gamma) mRNA. The results were compared between the treated and untreated sides of
      exposed patients, as well as with nontreated controls. RESULTS: Twenty-one
      patients consented to participate in the study. The number of CD3-, MBP-, and
      tryptase-positive cells was significantly less in the treated and untreated sides
      of exposed patients, compared with unexposed controls. IL-4 and IL-5 mRNA were
      significantly downregulated in the treated side of allergic patients, as compared
      with nontreated patients. This effect could not be shown for IL-4 in nonallergic
      patients. CONCLUSIONS: Topical steroid therapy had an anti-inflammatory effect on
      both allergic and nonallergic chronic sinusitis patients. The unilateral
      application of the steroid spray affected the contralateral side as well.

PMID- 9917048
TI  - A preliminary study of cocaine absorption from the nasal mucosa.
AB  - OBJECTIVE/HYPOTHESIS: To determine factors affecting the safe use of topical
      cocaine for anesthesia and vasoconstriction during rhinologic surgery. STUDY
      DESIGN: Prospective, randomized study of the kinetics of cocaine absorption
      through human nasal mucosa in 12 consecutive patients without nasal mucosal
      disease who were having septoplasty or septorhinoplasty. METHODS: With patients
      under general anesthesia, cocaine was applied topically to each nasal cavity by
      using cottonoid pledgets. Group I received 4 mL of a 4% solution (160 mg) of
      cocaine for 10 min, Group II received 4 mL of a 4% solution (160 mg) of cocaine
      for 20 min, and Group III received 4 mL of a 10% solution (400 mg) of cocaine for
      20 min. Absorption rate was determined by measuring serum cocaine concentration
      at intervals of 5, 10, 15, and 20 min. Residual cocaine was extracted from the
      pledgets and was analyzed quantitatively by using gas chromatography and mass
      spectroscopy. RESULTS: Of total cocaine applied, 35% was absorbed systemically:
      17% was absorbed within 5 min, 25% within 10 min, and 32% within 15 min. Of the
      cocaine absorbed, 47% was absorbed within the first 5 min, 70% within 10 min, and
      90% within 15 min. Two patients (16.6%), both in Group III, had intraoperative
      hypertension; one of these patients also had transient ventricular tachycardia.
      CONCLUSIONS: Although a 4% solution of cocaine applied to the nasal mucosa on
      cottonoid pledgets for 20 min is safe, we observed an idiosyncratic absorption
      rate four times greater than expected; therefore, we advise against topical use
      of a 10% cocaine solution for anesthesia and vasoconstriction during rhinologic
      surgery.

PMID- 9917050
TI  - Effects of atropine and scopolamine on bradycardia and emetic symptoms in
      otoplasty.
AB  - OBJECTIVE: To assess the effects of unilateral or bilateral otoplasty on
      bradycardia and postoperative nausea and vomiting (PONV) and the efficiency of
      transdermal scopolamine in the prophylaxis of PONV. STUDY DESIGN: Post hoc
      assessment of the data from a double-blind, randomized study. METHODS: Fifty
      otoplasty patients were studied; half of them received randomly and in double
      blind fashion a transdermal therapeutic system (patch) of scopolamine (TTS
      scopolamine) as prophylaxis against PONV before general anesthesia. The placebo
      group received atropine 10 microg x kg(-1) intravenously during induction.
      RESULTS: The scopolamine-treated patients suffered more from moderate
      peroperative bradycardia (8/25; P < .05) than the atropine-treated patients
      (1/25). Two patients wearing a half of the TTS-scopolamine patch needed
      intravenous atropine. After unilateral otoplasty, none of the TTS-scopolamine
      treated patients and 50% of the atropine-treated patients suffered from PONV.
      After bilateral operation, the respective incidences were 39% and 81% (P < .01).
      After unilateral otoplasty no patient needed droperidol, but after bilateral
      otoplasty, 12 of 19 of the atropine-treated and 4 of 18 (P < .05) of the
      scopolamine-treated patients needed droperidol. The mean numbers of doses of
      droperidol were 0.8+/-0.9 and 0.3+/-0.6 (P < .05), respectively. Two additional
      patients, wearing half of the TTS-scopolamine patch, suffered from mild central
      anticholinergic syndrome. CONCLUSION: TTS-scopolamine offers effective
      prophylaxis against PONV (auriculoemetic reflex), but does not protect from
      bradycardia (auriculocardiac reflex) in otoplasty. Cutting of the TTS-scopolamine
      patch may lead to undesirable side effects.

PMID- 9917049
TI  - Ciliary activity in differentiating and reactivated human respiratory epithelial
      cells.
AB  - OBJECTIVE: Experimental studies of mucociliary clearance, especially those
      involving drug effects, suffer from the difficulty of determining whether drugs
      act directly on ciliary motility or whether their effects are indirect, acting
      via changes in cell metabolism, viscous load, or alternative mechanisms. The
      present study provides a solution to this problem by comparing the motile
      characteristics of ciliated cells that have differentiated in primary cell
      culture with those of demembranated cilia reactivated with MgATP. METHODS: Human
      respiratory epithelial cells (REC) were dissociated from trachea, bronchus, nasal
      polyps, or turbinates and then placed in a dissociated cell culture system.
      Thirty-three percent of the dissociated cells contain beating cilia. Following 1
      week in culture, the REC dedifferentiated, but then redifferentiated within 96
      hours after they were brought to an air interface. RESULTS: The cilia on such
      cells beat with planar waves consisting of power and recovery strokes. Beat
      frequencies at 20 degrees C were 15+/-2.3 Hz. Ciliary beating often was
      coordinated both within and between cells with a defined antilaeoplectic pattern
      of coordination. Either fresh or cultured cells could be demembranated with
      Triton X-100 and reactivated with MgATP. The activity of these reactivated models
      was equivalent to those observed in living cells. CONCLUSION: The authors have
      demonstrated that ciliary beat frequency of demembranated human respiratory
      epithelial cells can be modulated by MgATP and can be adjusted to the same level
      of activity as measured in living cells. This allows them to selectively test
      whether a drug's effects on mucociliary transport are the result of direct
      interactions with the ciliary apparatus or are produced through other indirect
      mechanisms.

PMID- 9917051
TI  - Biomechanics of A-to-T flap design.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to determine the vertical
      height, horizontal incision width, and extent of undermining that correlated with
      the lowest closure tension. STUDY DESIGN: Prospective, cadaver study. METHODS:
      Forty "A-to-T" flaps were made on the torso and lower extremities of fresh
      cadavers. Ten flaps each were designed at heights of three, four, and five defect
      radii. Closing tensions were measured for each of these flaps initially, followed
      by serial base extensions. Based on the information from these first flaps, 10
      additional flaps were made at the optimal height and base extensions. These flaps
      were then serially undermined and tension measurements taken. RESULTS: Our
      results suggest that making the vertical height of the "A" twice the height of
      the defect yields a significant decrease in tension of closure when compared with
      a vertical height one and a half times the defect (P < .01), while increasing the
      height to two and a half times the defect height provides only a minimal further
      reduction in closure tension. Extending the base (horizontal) incision one defect
      diameter in each direction offers the greatest reduction in closing tension.
      Undermining up to three times the diameter of the defect offers progressive
      improvement in the tension of closure, while further undermining confers little
      additional benefit. CONCLUSIONS: Our findings indicate that the ideal A-to-T flap
      is designed to be twice the height of the original defect, with base extensions
      one defect diameter in each direction, and undermined to three times the diameter
      of the defect.

PMID- 9917052
TI  - Thyroid cartilage fracture repair in rabbits: comparing healing with wire and
      miniplate fixation.
AB  - OBJECTIVES: Evaluate cartilaginous healing in rabbits in response to surgically
      created thyroid cartilage fractures. Compare healing between laryngeal fracture
      repair techniques. STUDY DESIGN: Animal model. MATERIALS AND METHODS:
      Laryngectomy specimens were analyzed at 10 weeks, following paired wire fixation
      (n = 7) and miniplate fixation (n = 7) of thyroid cartilage fractures. RESULTS:
      Cartilaginous unions were present in all seven of the miniplated repairs, while
      fibrous unions were present in six of the wired repairs. The measure of
      distraction at the fracture site was significantly greater in the wired repairs
      compared with the plated repairs (P = .005). Furthermore, in five of seven
      miniplated repairs no distraction at the healed fracture site was present.
      CONCLUSIONS: The results demonstrate the ease, tolerability, and superiority of
      the miniplate fixation technique for the thyroid cartilage fractures, based on a
      rabbit model.

PMID- 9917053
TI  - Gustatory disturbance due to cerebrovascular disorder.
AB  - OBJECTIVES: Review three cases of unilateral gustatory disturbance due to central
      lesions caused by cerebrovascular disorders, describe clinical findings and the
      results of taste examinations, and discuss the central gustatory pathways in
      humans. STUDY DESIGN: Retrospective review of three gustatory disturbance cases
      due to cerebrovascular disorders. Additional review of 12 cases with central
      gustatory disturbance that have been reported. METHODS: Central lesions of three
      cases were examined by magnetic resonance imaging or computed tomography scan.
      Electrogustometry and a filter paper disk assay using taste solutions were
      performed in these cases for each of the bilateral gustatory nerves. RESULTS: In
      one case of pontine infarct, gustatory disturbance ipsilateral to the lesion was
      found, and in one case of thalamic infarct and one case of internal capsular
      infarct, gustatory disturbance contralateral to the lesion was observed.
      CONCLUSIONS: Fifteen cases of unilateral gustatory disturbance due to central
      lesions, including the present cases, have been reported to our knowledge.
      Examination of these cases strongly suggested that the central gustatory pathways
      in humans ascend ipsilaterally from the solitary nucleus of medulla oblongata to
      the pons, and from the pons, cross to a higher position in midbrain and reach the
      thalamus contralaterally.

PMID- 9917054
TI  - Pervasive developmental delay in children presenting as possible hearing loss.
AB  - OBJECTIVE/HYPOTHESIS: Children who fail to develop adequate language skills
      and/or appropriate social skills by age 2 years often are referred to the
      department of otolaryngology for otolaryngologic examination and evaluation of
      possible hearing deficits. Discovering a gross disparity between hearing function
      and language ability often uncovers an underlying developmental disorder
      satisfying criteria for diagnosis on the spectrum of autism and pervasive
      developmental delay (PDD). The otolaryngologist has a unique opportunity to
      identify these autistic children and initiate their evaluation and management.
      STUDY DESIGN: Retrospective review. METHODS: Review of charts of children
      referred over the past 4 years to the Department of Otolaryngology for possible
      hearing loss identified 15 children who were later diagnosed with PDD. RESULTS:
      Fifteen children initially referred for hearing evaluation were subsequently
      identified with a diagnosis of PDD. Males outnumbered females 4 to 1, with the
      average age of referral being 2 years. One third of the patients displayed middle
      ear disease that improved with PE tube placement. One third of the patients
      showed brainstem conduction dysfunction on auditory brainstem evoked response
      testing. CONCLUSIONS: Children with developmental delays, especially higher
      functioning ones, may present with a myriad of language and communication
      deficits that are often mistakenly attributed to hearing loss. Otolaryngologists
      and audiologists can assist in their early identification and appropriate
      referral for therapy.

PMID- 9917055
TI  - Laryngeal motion during exercise.
AB  - OBJECTIVE: To compare laryngoscopically observed changes in the larynx during
      exercise in persons with exercise-induced laryngomalacia (EIL) with changes in
      asymptomatic control subjects. STUDY DESIGN: Clinical study using a standardized
      exercise protocol. METHODS: Subjects exercised on an incremental ergometer:
      videotaped recordings of the larynx were obtained through the entire exercise;
      pulmonary function tests were completed before and/or immediately after the
      exercise. RESULTS: Laryngeal lumen size decreases during exercise in subjects
      with EIL. CONCLUSION: Subjects with EIL had a significant decrease in laryngeal
      lumen size during exercise compared with asymptomatic control subjects.

PMID- 9917056
TI  - Long-term follow-up of juvenile nasopharyngeal angiofibromas: analysis of
      recurrences.
AB  - OBJECTIVES: Juvenile nasopharyngeal angiofibroma often recurs if the tumor is
      large. This report is a long-term follow-up of these cases. It establishes the
      prognostic values of tumor extensions, analyzes the anatomic factors involved in
      recurrences, describes the spontaneous evolution of remnants based on a
      radiographic follow-up, and evaluates the pertinence of complex combined surgical
      approaches for invasive tumors and the value of complementary endoscopy. STUDY
      DESIGN: Retrospective review of 44 cases treated between 1985 and 1996. METHODS:
      Statistical analysis of the correlation between recurrence and tumor extension as
      evaluated by systematic analysis of 18 putative tumor extensions on preoperative
      computed tomography scans. RESULTS: Invasion of the skull base affected two
      thirds of the patients, and the rate of recurrence was 27.5%. Extensions to the
      infratemporal fossa, sphenoid sinus, base of pterygoids and clivus, the cavernous
      sinus (medial), foramen lacerum, and anterior fossa were correlated with more
      frequent recurrence. Long-term radiographic follow-up revealed putative residual
      disease in nine asymptomatic patients: these remnants gradually involuted.
      CONCLUSIONS: The data in the current study emphasize the prognostic value of
      skull base invasion and the difficulty of complete resection of extended lesions.
      Tumor remnants detected in symptom-free patients should be kept under
      surveillance by repeated computed tomography scan, since involution may occur.
      Recurrent symptoms may be treated by radiotherapy (30 Gy) rather than by extended
      combined procedures. Endoscopic surgery should be combined with surgery for
      better control of skull base extensions.

PMID- 9917057
TI  - Nitric oxide synthase activity in human squamous cell carcinoma of the head and
      neck.
AB  - OBJECTIVES: To test whether nitric oxide synthase (NOS) is expressed in primary
      otolaryngologic tumors and whether this expression is associated with the degree
      of malignancy. STUDY DESIGN: Twenty-six samples from the primary localization of
      human pharyngolaryngeal squamous cell carcinoma. MATERIALS AND METHODS: the
      activity of calcium-dependent and calcium-independent NOS was analyzed by the
      conversion of L-[14C]-arginine into L-[14C]-citrulline. RESULTS: NOS activity is
      below detectable levels in pharyngolaryngeal mucosa from noncancer patients. In
      the primary localization of the tumor, calcium-independent NOS activity is
      maximal at early stages of tumor growth, whereas calcium-dependent activity
      increases from early to advanced stages. CONCLUSIONS: These data suggest that
      tumor growth and malignancy is associated with a change in the enzymatic source
      of NO from calcium-independent NOS to calcium-dependent NOS isoform in primary
      localization. These data suggest that the inhibition of calcium-independent NOS
      activity in early stages and/or inhibition of calcium-dependent NOS activity in
      later stages could delay growth of solid tumors.

PMID- 9917058
TI  - Early outcome and complications of the extended subcranial approach to the
      anterior skull base.
AB  - OBJECTIVES: To present the technique of the extended subcranial approach to the
      anterior skull base and to review the results in 55 patients who underwent the
      procedure. STUDY DESIGN: Retrospective review of the records of 55 patients who
      underwent the extended subcranial approach to the anterior skull base between
      1994 and 1998 for the treatment of various neoplasms originating in the nasal
      cavity, nasopharynx, paranasal sinuses, orbit, or meninges, as well as for the
      repair of complex craniofacial trauma and/or cerebrospinal fluid (CSF) leak.
      Preoperative patient evaluation and the surgical technique are also reviewed.
      METHODS: Patient records were retrospectively reviewed and tabulated for age,
      sex, and indications for procedure, with special focus on early outcome and
      complications. RESULTS: Twenty-six patients underwent oncologic resections, 22
      patients had reduction of complex fronto-naso-orbital and skull base fractures,
      and seven patients had repair of CSF leak. Significant complications in the
      oncologic group consisted of one hematoma requiring needle aspiration and two
      cases of temporary nontension pneumocephalus. In the fracture group, one patient
      died because of extensive intracerebral damage and multiorgan failure, and one
      patient had nontension pneumocephalus coupled with CSF leakage and one patient
      had temporary nontension pneumocephalus. The most common late complication in all
      three groups was anosmia. CONCLUSIONS: Based on their review, the authors
      conclude that the extended subcranial approach to the anterior skull base is a
      safe, versatile, and effective procedure for the surgical treatment of various
      pathological conditions involving the anterior skull base.

PMID- 9917059
TI  - Gastrostomy tube insertion during rectus free flap harvest: indications,
      technique, and outcome.

PMID- 9917060
TI  - Botulinum toxin as an adjunct for the treatment of acute anteromedial arytenoid
      dislocation.

PMID- 9917061
TI  - Use of bone wax in the prevention of cerebrospinal fluid fistula in acoustic
      neuroma surgery.

PMID- 9917062
TI  - Sequence specificity of in vivo reverse splicing of the Tetrahymena group I
      intron.
AB  - Reverse splicing of group I introns is proposed to be a mechanism by which intron
      sequences are transferred to new genes. Integration of the Tetrahymena intron
      into the Escherichia coli 23S rRNA via reverse splicing depends on base pairing
      between the guide sequence of the intron and the target site. To investigate the
      substrate specificity of reverse splicing, the wild-type and 18 mutant introns
      with different guide sequences were expressed in E. coli. Amplification of intron
      rRNA junctions by RT-PCR revealed partial reverse splicing at 69 sites and
      complete integration at one novel site in the 23S rRNA. Reverse splicing was not
      observed at some potential target sites, whereas other regions of the 23S rRNA
      were more reactive than expected. The results indicate that the frequency of
      reverse splicing is modulated by the structure of the rRNA. The intron is spliced
      10-fold less efficiently in E. coli from a novel integration site (U2074) in
      domain V of the 23S rRNA than from a site homologous to the natural splice
      junction of the Tetrahymena 26S rRNA, suggesting that the forward reaction is
      less favored at this site.

PMID- 9917063
TI  - The clam 3' UTR masking element-binding protein p82 is a member of the CPEB
      family.
AB  - During early development gene expression is controlled principally at the
      translational level. Oocytes of the surf clam Spisula solidissima contain large
      stockpiles of maternal mRNAs that are translationally dormant or masked until
      meiotic maturation. Activation of the oocyte by fertilization leads to
      translational activation of the abundant cyclin and ribonucleotide reductase
      mRNAs at a time when they undergo cytoplasmic polyadenylation. In vitro unmasking
      assays have defined U-rich regions located approximately centrally in the 3' UTRs
      of these mRNAs as translational masking elements. A clam oocyte protein of 82
      kDa, p82, which selectively binds the masking elements, has been proposed to act
      as a translational repressor. Importantly, mRNA-specific unmasking in vitro
      occurs in the absence of poly(A) extension. Here we show that clam p82 is related
      to Xenopus CPEB, an RNA-binding protein that interacts with the U-rich
      cytoplasmic polyadenylation elements (CPEs) of maternal mRNAs and promotes their
      polyadenylation. Cloned clam p82/CPEB shows extensive homology to Xenopus CPEB
      and related polypeptides from mouse, goldfish, Drosophila and Caenorhabditis
      elegans, particularly in their RNA-binding C-terminal halves. Two short N
      terminal islands of sequence, of unknown function, are common to vertebrate CPEBs
      and clam p82. p82 undergoes rapid phosphorylation either directly or indirectly
      by cdc2 kinase after fertilization in meiotically maturing clam oocytes, prior to
      its degradation during the first cell cleavage. Phosphorylation precedes and,
      according to inhibitor studies, may be required for translational activation of
      maternal mRNA. These data suggest that clam p82 may be a functional homolog of
      Xenopus CPEB.

PMID- 9917064
TI  - Dual roles of p82, the clam CPEB homolog, in cytoplasmic polyadenylation and
      translational masking.
AB  - In the transcriptionally inert maturing oocyte and early embryo, control of gene
      expression is largely mediated by regulated changes in translational activity of
      maternal mRNAs. Some mRNAs are activated in response to poly(A) tail lengthening;
      in other cases activation results from de-repression of the inactive or masked
      mRNA. The 3' UTR cis-acting elements that direct these changes are defined,
      principally in Xenopus and mouse, and the study of their trans-acting binding
      factors is just beginning to shed light on the mechanism and regulation of
      cytoplasmic polyadenylation and translational masking. In the marine
      invertebrate, Spisula solidissima, the timing of activation of three abundant
      mRNAs (encoding cyclin A and B and the small subunit of ribonucleotide reductase,
      RR) in fertilized oocytes correlates with their cytoplasmic polyadenylation.
      However, in vitro, mRNA-specific unmasking occurs in the absence of
      polyadenylation. In Walker et al. (in this issue) we showed that p82, a protein
      defined as selectively binding the 3' UTR masking elements, is a homolog of
      Xenopus CPEB (cytoplasmic polyadenylation element binding protein). In functional
      studies reported here, the elements that support polyadenylation in clam egg
      lysates include multiple U-rich CPE-like motifs as well as the nuclear
      polyadenylation signal AAUAAA. This represents the first detailed analysis of
      invertebrate cis-acting cytoplasmic polyadenylation signals. Polyadenylation
      activity correlates with p82 binding in wild-type and CPE-mutant RR 3' UTR RNAs.
      Moreover, since anti-p82 antibodies specifically neutralize polyadenylation in
      egg lysates, we conclude that clam p82 is a functional homolog of Xenopus CPEB,
      and plays a positive role in polyadenylation. Anti-p82 antibodies also result in
      specific translational activation of masked mRNAs in oocyte lysates, lending
      support to our original model of clam p82 as a translational repressor. We
      propose therefore that clam p82/CPEB has dual functions in masking and
      cytoplasmic polyadenylation.

PMID- 9917065
TI  - A minor fraction of basic fibroblast growth factor mRNA is deaminated in Xenopus
      stage VI and matured oocytes.
AB  - Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine in
      double-stranded regions of RNA. ADAR activity is in the nucleus in Xenopus laevis
      stage VI oocytes, and released into the cytoplasm at oocyte maturation. We
      previously demonstrated that a cytoplasmic double-stranded RNA (dsRNA) binding
      factor(s), cyto-dsRBP, protects microinjected dsRNA from the ADAR released at
      maturation. Here we describe experiments to determine whether an endogenous
      dsRNA, the duplex formed between sense and antisense transcripts of basic
      fibroblast growth factor (bFGF), is protected in a similar manner. Consistent
      with the presence of cyto-dsRBP, we observed that the majority of bFGF RNA was
      not deaminated, before or after maturation. However, a minor fraction of the bFGF
      RNA was deaminated whether the RNA was isolated from stage VI oocytes or matured
      oocytes. Since ADAR activity is in the nucleus in stage VI oocytes, our results
      suggest that a fraction of the bFGF RNAs are hybridized in the nucleus and are
      ADAR substrates. Adenosine deaminations result in A-to-G changes in cDNAs, so we
      quantified the fraction of modified molecules using restriction-enzyme assays of
      RT-PCR products. Caveats due to recombination during RT-PCR are discussed.

PMID- 9917066
TI  - Molecular genetic analysis of U2AF59 in Schizosaccharomyces pombe: differential
      sensitivity of introns to mutational inactivation.
AB  - The large subunit of the mammalian U2AF heterodimer (U2AF65) is essential for
      splicing in vitro. To expand our understanding of how this protein functions in
      vivo, we have created a null allele of the gene encoding the Schizosaccharomyces
      pombe ortholog, U2AF59, and employed it in a variety of genetic complementation
      assays. First, analysis of an extensive series of double amino acid substitutions
      indicates that this splicing factor is surprisingly refractory to mutations.
      Second, despite extensive structural conservation, we find that metazoan large
      subunit orthologs cannot substitute in vivo for fission yeast U2AF59. Third,
      because the activity of U2AF65 in vitro involves binding to the 3' polypyrimidine
      tract, we examined the splicing of introns containing or lacking this feature in
      a U2AF59 mutant described here as well as a previously isolated temperature
      sensitive mutant (Potashkin et al., 1993, Science 262:573-575). Our data indicate
      that all four introns tested, including two that lack extensive runs of
      pyrimidines between the branchpoint and 3' splice site, show splicing defects
      upon shifting to the nonpermissive condition. In all cases, splicing is blocked
      prior to the first transesterification reaction in the mutants, consistent with
      the role inferred for human U2AF65 based on in vitro experiments.

PMID- 9917067
TI  - The yeast Saccharomyces cerevisiae YDL112w ORF encodes the putative 2'-O-ribose
      methyltransferase catalyzing the formation of Gm18 in tRNAs.
AB  - The protein sequences of three known RNA 2'-O-ribose methylases were used as
      probes for detecting putative homologs through iterative searches of genomic
      databases. We have identified 45 new positive Open Reading Frames (ORFs), mostly
      in prokaryotic genomes. Five complete eukaryotic ORFs were also detected, among
      which was a single ORF (YDL112w) in the yeast Saccharomyces cerevisiae genome.
      After genetic depletion of YDL112w, we observed a specific defect in tRNA ribose
      methylation, with the complete disappearance of Gm18 in all tRNAs that naturally
      contain this modification, whereas other tRNA ribose methylations and the complex
      pattern of rRNA ribose methylations were not affected. The tRNA G18 methylation
      defect was suppressed by transformation of the disrupted strain with a plasmid
      allowing expression of YDL112wp. The formation of Gm18 on an in vitro transcript
      of a yeast tRNASer naturally containing this methylation, which was efficiently
      catalyzed by cell-free extracts from the wild-type yeast strain, did not occur
      with extracts from the disrupted strain. The protein encoded by the YDL112w ORF,
      termed Trm3 (tRNA methylation), is therefore likely to be the tRNA (Gm18) ribose
      methylase. In in vitro assays, its activity is strongly dependent on tRNA
      architecture. Trm3p, the first putative tRNA ribose methylase identified in an
      eukaryotic organism, is considerably larger than its Escherichia coli functional
      homolog spoU (1,436 amino acids vs. 229 amino acids), or any known or putative
      prokaryotic RNA ribose methyltransferase. Homologs found in human (TRP-185
      protein), Caenorhabditis elegans and Arabidopsis thaliana also exhibit a very
      long N-terminal extension not related to any protein sequence in databases.

PMID- 9917068
TI  - Identification of the ribosome binding sites of translation initiation factor IF3
      by multidimensional heteronuclear NMR spectroscopy.
AB  - Titrations of Escherichia coli translation initiation factor IF3, isotopically
      labeled with 15N, with 30S ribosomal subunits were followed by NMR by recording
      two-dimensional (15N,1H)-HSQC spectra. In the titrations, intensity changes are
      observed for cross peaks belonging to amides of individual amino acids. At low
      concentrations of ribosomal subunits, only resonances belonging to amino acids of
      the C-domain of IF3 are affected, whereas all those attributed to the N-domain
      are still visible. Upon addition of a larger amount of 30S subunits cross peaks
      belonging to residues of the N-terminal domain of the protein are also
      selectively affected. Our results demonstrate that the two domains of IF3 are
      functionally independent, each interacting with a different affinity with the
      ribosomal subunits, thus allowing the identification of the individual residues
      of the two domains involved in this interaction. Overall, the C-domain interacts
      with the 30S subunits primarily through some of its loops and alpha-helices and
      the residues involved in ribosome binding are distributed rather symmetrically
      over a fairly large surface of the domain, while the N-domain interacts mainly
      via a small number of residues distributed asymmetrically in this domain. The
      spatial organization of the active sites of IF3, emerging through the comparison
      of the present data with the previous chemical modification and mutagenesis data,
      is discussed in light of the ribosomal localization of IF3 and of the mechanism
      of action of this factor.

PMID- 9917069
TI  - Core sequence in the RNA motif recognized by the ErmE methyltransferase revealed
      by relaxing the fidelity of the enzyme for its target.
AB  - Under physiological conditions, the ErmE methyltransferase specifically modifies
      a single adenosine within ribosomal RNA (rRNA), and thereby confers resistance to
      multiple antibiotics. The adenosine (A2058 in Escherichia coli 23S rRNA) lies
      within a highly conserved structure, and is methylated efficiently, and with
      equally high fidelity, in rRNAs from phylogenetically diverse bacteria. However,
      the fidelity of ErmE is reduced when magnesium is removed, and over twenty new
      sites of ErmE methylation appear in E. coli 16S and 23S rRNAs. These sites show
      widely different degrees of reactivity to ErmE. The canonical A2058 site is
      largely unaffected by magnesium depletion and remains the most reactive site in
      the rRNA. This suggests that methylation at the new sites results from changes in
      the RNA substrate rather than the methyltransferase. Chemical probing confirms
      that the rRNA structure opens upon magnesium depletion, exposing potential new
      interaction sites to the enzyme. The new ErmE sites show homology with the
      canonical A2058 site, and have the consensus sequence aNNNcgGAHAg (ErmE
      methylation occurs exclusively at adenosines (underlined); these are preceded by
      a guanosine, equivalent to G2057; there is a high preference for the adenosine
      equivalent to A2060; H is any nucleotide except G; N is any nucleotide; and there
      are slight preferences for the nucleotides shown in lower case). This consensus
      is believed to represent the core of the motif that Erm methyltransferases
      recognize at their canonical A2058 site. The data also reveal constraints on the
      higher order structure of the motif that affect methyltransferase recognition.

PMID- 9917072
TI  - Crystallographic studies of RNA hairpins in complexes with recombinant MS2
      capsids: implications for binding requirements.
AB  - The coat protein of bacteriophage MS2 is known to bind specifically to an RNA
      hairpin formed within the MS2 genome. Structurally this hairpin is built up by an
      RNA double helix interrupted by one unpaired nucleotide and closed by a four
      nucleotide loop. We have performed crystallographic studies of complexes between
      MS2 coat protein capsids and four RNA hairpin variants in order to evaluate the
      minimal requirements for tight binding to the coat protein and to obtain more
      information about the three-dimensional structure of these hairpins. An RNA
      fragment including the four loop nucleotides and a two-base-pair stem but without
      the unpaired nucleotide is sufficient for binding to the coat protein shell under
      the conditions used in this study. In contrast, an RNA fragment containing a stem
      with the unpaired nucleotide but missing the loop nucleotides does not bind to
      the protein shell.

PMID- 9917070
TI  - Guanosine 2-NH2 groups of Escherichia coli RNase P RNA involved in intramolecular
      tertiary contacts and direct interactions with tRNA.
AB  - We have identified by nucleotide analog interference mapping (NAIM) exocyclic NH2
      groups of guanosines in RNase P RNA from Escherichia coli that are important for
      tRNA binding. The majority of affected guanosines represent phylogenetically
      conserved nucleotides. Several sites of interference could be assigned to direct
      contacts with the tRNA moiety, whereas others were interpreted as reflecting
      indirect effects on tRNA binding due to the disruption of tertiary contacts
      within the catalytic RNA. Our results support the involvement of the 2-NH2 groups
      of G292/G293 in pairing with C74 and C75 of tRNA CCA-termini, as well as
      formation of two consecutive base triples involving C75 and A76 of CCA-ends
      interacting with G292/A258 and G291/G259, respectively. Moreover, we present
      first biochemical evidence for two tertiary contacts (L18/P8 and L8/P4) within
      the catalytic RNA, whose formation has been postulated previously on the basis of
      phylogenetic comparative analyses. The tRNA binding interference data obtained in
      this and our previous studies are consistent with the formation of a consecutive
      nucleotide triple and quadruple between the tetraloop L18 and helix P8. Formation
      of the nucleotide triple (G316 and A94:U104 in wild-type E. coli RNase P RNA) is
      also supported by mutational analysis. For the mutant RNase P RNA carrying a
      G94:C104 double mutation, an additional G316-to-A mutation resulted in a
      restoration of binding affinity for mature and precursor tRNA.

PMID- 9917071
TI  - Coordinate repression of a trio of neuron-specific splicing events by the
      splicing regulator PTB.
AB  - In this study, we demonstrate the ability of the polypyrimidine tract binding
      protein PTB to function as a coordinator of splicing regulation for a trio of
      neuron-specific exons that are subject to developmental splicing changes in the
      rat cerebellum. Three neuron-specific exons that show positive regulation are
      derived from the GABA(A) receptor gamma2 subunit 24 nucleotide exon, clathrin
      light chain B exon EN, and N-methyl-D-aspartate receptor NR1 subunit exon 5 pre
      mRNAs. The functional activity of splicing repressor signals located in the 3'
      splice site regions adjacent to the neural exons is shown using an alternative
      splicing switch assay, in which these short RNA sequences function in trans to
      switch splicing to the neural pathway in HeLa splicing reactions. Parallel UV
      crosslinking/competition assays demonstrate selective binding of PTB in
      comparison to substantially lower binding at adjacent, nonneural 3' splice sites.
      Substantially lower PTB binding and splicing switch activity is also observed for
      the 3' splice site of NMDA exon 21, which is subject to negative regulation in
      cerebellum tissue in the same time frame. In splicing active neural extracts, the
      balance of control shifts to positive regulation, and this shift correlates with
      a PTB status that is predominantly the neural form. In this context, the addition
      of recombinant PTB is sufficient to switch splicing to the nonneural pathway. The
      neural extracts also reveal specific binding of the CUG triplet repeat binding
      protein to a subset of regulatory 3' splice site regions. These interactions may
      interfere with PTB function or modulate splicing levels in a substrate-specific
      manner within neural tissue. Together these results strengthen the evidence that
      PTB is a splicing regulator with multiple targets and demonstrate its ability to
      discriminate among neural and nonneural substrates. Thus, a variety of mechanisms
      that counterbalance the splicing repressor function of PTB in neural tissue are
      capable of mediating developmental splicing control. Altered expression of PTB
      isoforms during cerebellar development, as documented by Western blot analysis,
      is proposed to be a contributing mechanism.

PMID- 9917074
TI  - Problems with monitoring heparin anticoagulation.

PMID- 9917073
TI  - Maturation of 23S ribosomal RNA requires the exoribonuclease RNase T.
AB  - Ribosomal RNAs are generally synthesized as long, primary transcripts that must
      be extensively processed to generate the mature, functional species. In
      Escherichia coli, it is known that the initial 30S precursor is cleaved during
      its synthesis by the endonuclease RNase III to generate precursors to the 16S,
      23S, and 5S rRNAs. However, despite extensive study, the processes by which these
      intermediate products are converted to their mature forms are poorly understood.
      In this article, we describe the maturation of 23S rRNA. Based on Northern
      analysis of RNA isolated from a variety of mutant strains lacking one or multiple
      ribonucleases, we show that maturation of the 3' terminus requires the action of
      RNase T, an enzyme previously implicated in the end turnover of tRNA and in the
      maturation of small, stable RNAs. Although other exoribonucleases can participate
      in shortening the 3' end of the initial RNase III cleavage product, RNase T is
      required for removal of the last few residues. In the absence of RNase T, 23S
      rRNA products with extra 3' residues accumulate and are incorporated into
      ribosomes, with only small effects on cell growth. Purified RNase T accurately
      and efficiently converts these immature ribosomes to their mature forms in vitro,
      whereas free RNA is processed relatively poorly. In vivo, the processing defect
      at the 3' end has no effect on 5' maturation, indicating that the latter process
      proceeds independently. We also find that a portion of the 23S rRNA that
      accumulates in many RNase T- cells becomes polyadenylated because of the action
      of poly(A) polymerase I. The requirement for RNase T in 23S rRNA maturation is
      discussed in relation to a model in which only this enzyme, among the eight
      exoribonucleases present in E. coli, is able to efficiently remove nucleotides
      close to the double-stranded stem generated by the pairing of the 5' and 3'
      termini of most stable RNAs.

PMID- 9917075
TI  - Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of
      Parkinson's disease.
AB  - Tolcapone is a selective peripheral and central catechol-O-methyltransferase
      (COMT) inhibitor recently approved as adjunctive therapy in patients with
      idiopathic Parkinson's disease who are already being treated with a levodopa
      peripheral dopa decarboxylase inhibitor (DDI) combination. Tolcapone potentiates
      and prolongs the effect of levodopa in the central nervous system (CNS) by
      enhancing levodopa's delivery to the CNS and slowing dopamine's central
      metabolism. A short terminal disposition half-life of 2 hours mandates dosing 3
      times/day. Dosage adjustment is generally unnecessary in the presence of mild to
      moderate renal and hepatic impairment. Coadministration of tolcapone with
      levodopa-DDI results in significant amelioration of the wearing-off and on-off
      phenomena and frequently allows significant levodopa dosage reduction. In
      patients with stable disease, tolcapone improves "on" time. As might be expected
      from its potentiation of levodopa effects, dopaminergic side effects are
      prominent with this agent. Although the main objective of drug treatment in
      Parkinson's disease remains clinical improvement with an optimum dose and
      frequency of levodopa administration, tolcapone may prove a useful adjunct to
      such therapy, especially in the presence of the wearing-off and on-off phenomena.
      The relative merits of this agent vis-a-vis dopamine receptor agonists are
      somewhat unclear at present. However, recent guidelines from the American Academy
      of Neurology suggest that a COMT inhibitor be added to levodopa-dopamine agonist
      therapy in patients with advanced disease.

PMID- 9917076
TI  - Trovafloxacin: an overview.
AB  - Trovafloxacin, a new synthetic naphthyridine fluoroquinolone antibiotic, is a
      broad-spectrum agent available orally and intravenously. It was recently approved
      by the Food and Drug Administration for the treatment of selected pulmonary,
      surgical, intraabdominal, gynecologic, pelvic, skin, and urinary tract
      infections. Its spectrum of activity includes aerobic gram-positive and gram
      negative organisms as well as anaerobic pathogens. It is rapidly absorbed after
      oral administration, achieves good tissue and cerebrospinal fluid penetration,
      and has a half-life that allows once-daily dosing. It is hepatically metabolized,
      and dosage adjustments are necessary for patients with severe hepatic dysfunction
      but not for those with mild or moderate dysfunction or renal dysfunction. The
      drug has a favorable safety profile, and a high tendency for transient first-dose
      dizziness and/or lightheadedness in young women. Similar to other quinolones,
      trovafloxacin should not be taken with antacids that contain aluminum or
      magnesium, sucralfate, or ferrous sulfate. Trovafloxacin may prove beneficial as
      it allows for oral or intravenous monotherapy against indicated infections that
      normally require multidrug, broad-spectrum antibiotic coverage.

PMID- 9917077
TI  - Human immunodeficiency virus protease inhibitors.
AB  - Human immunodeficiency virus (HIV) protease inhibitors have revolutionized the
      treatment of individuals infected with this pathogen. The protease is an enzyme
      that is essential for viral replication because it cleaves both structural and
      functional proteins from precursor viral polyprotein strands. Inhibition of this
      process suppresses viral replication, which produces immature noninfectious
      virions. When combined with reverse transcriptase inhibitors, these agents are
      very potent in suppressing viral replication. Pharmacologic properties, toxic
      profile, drug interactions, and resistance patterns differ among protease
      inhibitors, and all must be considered when selecting the drugs for therapeutic
      use in humans. The best combination, sequence of use, durability of response, and
      magnitude of immune reconstitution and function are issues that have yet to be
      fully elucidated.

PMID- 9917078
TI  - Nitric oxide for ARDS--what is the evidence?
AB  - We critically reviewed English-language articles indexed on MEDLINE from 1966
      1998 and those cited in indexed articles describing or investigating
      administration of nitric oxide (NO) in adult respiratory distress syndrome
      (ARDS). Studies evaluating NO exclusively in the pediatric population and in
      conditions other than ARDS (chronic obstructive pulmonary disease, asthma,
      cardiac surgery, pulmonary hypertension) were excluded, as were those published
      exclusively as abstracts. Of the 22 papers selected, 5 studies were dose-response
      trials, eight were comparative, and the rest were noncomparative. Dose-dependent
      decreases in pulmonary artery pressures and increases in arterial oxygenation
      were observed; however, the minimal effective dose varied. Several short-term
      noncomparative and small noncomparative prospective trials concluded that NO
      improves oxygenation and decreases pulmonary vasoconstriction without effects on
      systemic hemodynamics. However, evidence that NO improves outcomes in patients
      with ARDS is insufficient because mortality remained high, and the number of
      subjects in each study was low. Since improvements in oxygenation are not seen in
      all patients and outcomes or mortality might not be altered, NO should be
      reserved for selected patients in whom conventional therapy is not sufficient to
      maintain acceptable oxygenation levels.

PMID- 9917079
TI  - Cyclospora: review of an emerging parasite.
AB  - Cyclospora is a parasite traditionally associated with diarrhea in travelers to
      endemic countries. Recently, several cases of cyclosporiasis were reported in
      nontravelers in the United States and Canada, implicating various fruits and
      vegetables as vehicles of infection. The life cycle of cyclospora is not fully
      known, but is believed to involve both asexual and sexual stages of
      proliferation. Food- and water-borne transmission of infection have been
      implicated. Patients infected with Cyclospora cayetanensis have protracted watery
      diarrhea. Various generalized symptoms are also present, making cyclosporiasis
      indistinguishable from infectious diarrhea caused by other microorganisms.
      Diagnosis depends on identifying the organism by microbiologic examination of
      stool samples. Treatment consists of supportive care, maintenance of fluid and
      electrolyte status, symptomatic relief, and antibiotic therapy. Trimethoprim
      sulfamethoxazole is the only antibiotic available that is effective in
      eradicating the organism.

PMID- 9917080
TI  - Options for the management of mucosal candidiasis in patients with AIDS and HIV
      infection.
AB  - Oropharyngeal candidiasis may be the first manifestation of human
      immunodeficiency viral (HIV) infection, and more than 90% of patients with the
      acquired immunodeficiency syndrome (AIDS) develop the disease. Although numerous
      antifungal agents are available, azoles, both topical (clotrimazole) and systemic
      (fluconazole, itraconazole), have largely replaced older topical antifungals
      (gentian violet, nystatin) in the management of the disease in these patients. A
      concern in these patients is clinical relapse, which appears to be dependent on
      degree of immunosuppression and is more common with clotrimazole and ketoconazole
      than with fluconazole or itraconazole. Candida esophagitis is also of concern,
      since it occurs in more than 10% of patients with AIDS. Fluconazole is an
      integral part of management. A cyclodextrin oral solution formulation of
      itraconazole has similar clinical response rates as fluconazole and is an
      effective alternative. In patients with fluconazole-resistant mucocutaneous
      candidiasis, treatment options include itraconazole and amphotericin B oral
      suspension and parenteral preparation.

PMID- 9917081
TI  - Slowing the initial titration rate of tramadol improves tolerability.
AB  - STUDY OBJECTIVES: To examine the effect of three titration schedules on the
      tolerability of tramadol, and to determine whether slow titration would reduce
      the frequency of drug discontinuation due to adverse events. DESIGN: Multicenter,
      outpatient, double-blind, parallel study. SETTING: Twenty-eight outpatient study
      centers. SUBJECTS: Four hundred sixty-five patients with chronic joint pain
      Interventions. Patients were randomized into one of four treatment groups for 14
      days: placebo, or tramadol dosage titrated at 1, 4, or 10 days to achieve the
      study target dosage of 200 mg/day. They continued taking their dosage of
      nonsteroidal antiinflammatory drug during the study. Each group was examined to
      determine if slower titration resulted in a statistically significant trend
      toward fewer discontinuations due to nausea and/or vomiting and dizziness and/or
      vertigo. Discontinuation due to any adverse event was similarly analyzed. If the
      trend was statistically significant, pairwise comparisons were performed to
      determine the statistical significance among titration rates. MEASUREMENTS AND
      MAIN RESULTS: A statistically significant trend was seen toward fewer
      discontinuations as a result of nausea/vomiting, dizziness/vertigo, and any
      adverse event as the titration rate decreased. Patients with 10-day titration
      rate required the fewest discontinuations, and this rate was statistically
      significantly different from both the 1- and 4-day rates for discontinuations.
      CONCLUSION: A slower rate of initiating tramadol therapy (50-mg increments every
      3 days) improved tolerability with significantly fewer discontinuations due to
      dizziness or vertigo.

PMID- 9917082
TI  - Comparison of 24-hour ambulatory blood pressure data in hypertensive patients
      switched from nifedipine-GITS to nifedipine-CC.
AB  - STUDY OBJECTIVE: To evaluate 24-hour blood pressure control and frequency of
      adverse effects in patients with mild to moderate hypertension switched from
      nifedipine gastrointestinal therapeutic system (Nif-GITS) to nifedipine coat core
      (Nif-CC). DESIGN: Open-label, prospective, switch study SETTING: University
      affiliated outpatient cardiology clinic. SUBJECTS: Twenty patients with mild to
      moderate essential hypertension, who were taking Nif-GITS 30, 60, or 90 mg/day
      for 8 weeks or longer. INTERVENTIONS: Patients stabilized with Nif-GITS 30, 60,
      or 90 mg were monitored over 24 hours with an ambulatory blood pressure monitor
      and were then switched to an equivalent dosage of Nif-CC. After 8 weeks+/-1 week
      taking Nif-CC, they were again monitored with a 24-hour blood pressure monitor.
      The 24-hour blood pressure load (percentage of values > 135/85 mm Hg for 24 hrs),
      daytime blood pressure load (percentage of values > 140/90 mm Hg from 7:00 A.M.
      10:00 P.M.), nighttime blood pressure load (percentage of values > 120/80 mm Hg
      from 10:00 P.M.-7:00 A.M.), diurnal blood pressure variation, average 24-hour
      blood pressure, daytime blood pressure, nighttime blood pressure, mean blood
      pressure for the first 4 hours, and last 8 hours of the dosing interval were
      measured. Adverse effects such as headache, dizziness, and edema were also
      reported. MEASUREMENTS AND MAIN RESULTS: No differences in average 24 hour-blood
      pressure readings were observed but significant differences in blood pressure
      control during the first 4 and last 8 hours of the dosing interval were seen.
      Systolic and diastolic blood pressures were higher after approximately 16 hours
      in patients switched from Nif-GITS to Nif-CC. Although Nif-CC caused a greater
      initial response, it was less effective than Nif-GITS after 16 hours. This could
      explain the lack of differences in average 24-hour blood pressure values between
      formulations. Of the 20 patients, 20% experienced increased headaches, 20% showed
      signs of increased peripheral edema, and 10% reported occasional dizziness after
      switching agents. Three patients discontinued Nif-CC, two as ordered by their
      primary care physician and one on his own due to headache. CONCLUSION: This study
      suggests that patients switched from Nif-GITS to Nif-CC could experience
      increased blood pressure during the night or toward the end of the dosing
      interval. They could also experience adverse effects such as headache, edema, and
      dizziness, which could result in more physician visits and put patients with
      other disease states such as coronary heart disease at increased risk.

PMID- 9917083
TI  - Pharmacodynamic profile of prolonged etoposide administration in patients with
      small cell lung cancer and non-Hodgkin's lymphoma.
AB  - STUDY OBJECTIVE: To determine whether therapeutic drug monitoring can enhance
      administration of etoposide in patients with drug-responsive neoplasms. DESIGN:
      Prospective, open-label study. SETTING: University-affiliated hospital and cancer
      center. PATIENTS: Sixteen patients with small cell lung cancer or low-grade non
      Hodgkin's lymphoma. INTERVENTIONS: Patients were treated with etoposide, 25
      mg/m2/day over 24 hours by continuous infusion for 35 days. Peripheral blood
      samples were collected twice a week to measure etoposide levels. Plasma was
      separated, frozen and stored at -20 degrees C until assayed. MEASUREMENTS AND
      MAIN RESULTS: Steady-state plasma etoposide concentrations (ECpss) were
      determined and used to calculate total systemic clearance (Clsys). Despite
      differences in dosage and administration schedules, etoposide Clsys was similar
      to previous reports. In addition, a biexponential relationship between ECpss and
      absolute neutrophil count was demonstrated by nonlinear least squares estimation.
      Values generated from this equation indicated that ECpss above 1.5 microg/ml was
      strongly associated with grade III-IV leukocyte toxicity. Although less precise,
      there may also be a correlation between ECpss and antitumor activity. CONCLUSION:
      Based on these findings, we propose a pharmacodynamic construct that uses
      measurements of both pharmacokinetic (ECpss, Clsys) and pharmacodynamic
      (hematologic toxicity, tumor response) parameters for patients with etoposide
      sensitive tumors. Therapeutic drug monitoring may be able to mitigate hematologic
      toxicity.

PMID- 9917084
TI  - Potential risk factors associated with thrombocytopenia in a surgical intensive
      care unit.
AB  - We conducted a retrospective chart review of 193 patients admitted during a 3
      month period to determine the frequency of and potential risk factors associated
      with thrombocytopenia, and the association of acquired thrombocytopenia with
      length of stay in a surgical-trauma intensive care unit (SICU) and mortality. All
      records were reviewed beginning 24 hours after admission. Patients were followed
      for the duration of SICU stay or until death. Data collected and analyzed as
      potential risk factors for thrombocytopenia were age, gender, admitting
      diagnosis, classification (trauma, surgical, medical), APACHE II score, medical
      history, all scheduled drugs with start and stop dates, select laboratory values,
      arterial or central line placement, and complications. Thrombocytopenia occurred
      in 25 (13%) patients. These patients were more likely (p<0.05) than those without
      thrombocytopenia to have the following potential risk factors: presence of a
      central or arterial line (76% vs 46%, p<0.025), nonsurgical diagnosis (60% vs
      37%, p<0.05), diagnosis of sepsis (p<0.001), and administration of phenytoin
      (p<0.01), piperacillin (p<0.005), imipenem-cilastatin (p<0.001), and vancomycin
      (p<0.005). A longer SICU stay (mean 21 vs 4.5 days, p<0.05) and increased
      mortality (16% vs 4%, p<0.05) were significantly associated with
      thrombocytopenia. Cefazolin administration was significantly associated with
      nonthrombocytopenia (p<0.05). Factors not associated with thrombocytopenia were
      age, gender, and administration of histamine2-receptor antagonists, heparin,
      enoxaparin, penicillins, ceftazidime, ceftriaxone, chloramphenicol, and
      amphotericin B. A central or arterial line was the only factor associated with
      the development of thrombocytopenia in a multiple linear regression analysis
      (p=0.0003, multiple r=0.2580). Thrombocytopenia is not a common occurrence in the
      SICU, but is associated with a longer SICU stay and increased mortality.

PMID- 9917085
TI  - A review of protease inhibitor-induced hyperglycemia.
AB  - Hyperglycemia is an adverse effect that occurs with all protease inhibitors,
      although few cases have been reported in the literature. Most patients with human
      immunodeficiency virus infection receiving antiretroviral therapy are also taking
      at least one protease inhibitor. Patients with a family history of diabetes
      mellitus may be at a greater risk of developing this adverse effect. It is
      therefore prudent to monitor all patients starting protease inhibitor therapy for
      the onset of diabetes or hyperglycemia, particularly those with a family history
      of diabetes. Baseline fasting plasma glucose or serum glucose level should be
      measured with follow-up measurements every 3 months for approximately 6-12
      months.

PMID- 9917086
TI  - Combination antifungal therapy for invasive aspergillosis infection in liver
      transplant recipients: report of two patients.
AB  - Invasive aspergillosis in solid organ transplant recipients is associated with
      mortality of approximately 100%. The search for optimal therapy has led
      clinicians to administer antifungal combinations. Two orthotopic liver transplant
      recipients developed invasive aspergillosis (pulmonary and perivertebral) after
      transplantation and were treated with combination antifungal therapy consisting
      of liposomal amphotericin B and itraconazole. Although both patients were
      initially stabilized, they died after 94 and 138 days of antifungal therapy,
      respectively. Presumably, aspergillosis was the principal cause of death.
      Antifungal serum concentrations and fungicidal titers in both patients indicated
      that the drugs may have been antagonistic and thus detrimental.

PMID- 9917087
TI  - Inhibition of peritoneal dissemination of murine colon carcinoma cells by
      administrating retrovirus harboring IL-2 gene.
AB  - We have examined the antitumor effect of the retrovirally expressed interleukin-2
      (IL-2) gene in murine colon carcinoma cells (Colon 26) on a disseminated model
      within the peritoneal cavity. Intraperitoneal injection of IL-2-producing Colon
      26, but not wild-type cells, into syngeneic mice did not cause animal death and
      conferred T-cell-dependent, tumor-specific protective immunity on the inoculated
      mice. Direct administration of the retrovirus harboring IL-2 gene into the
      peritoneal cavity of the mice that had intraperitoneal tumor of wild-type cells
      significantly prolonged the survival of the mice compared with that of the mice
      that received control retrovirus. In the surviving mice treated with the
      retrovirus we also observed the induction of protective immunity with tumor
      specificity. Integrated retrovirus DNA was not detected in any organs examined.
      Thus, in vivo IL-2 gene transfer by retrovirus enabled tumor-bearing mice to
      generate antitumor immunity without unnecessary retroviral insertion into host
      genome.

PMID- 9917088
TI  - Tumor necrosis factor-alpha-based gene therapy enhances radiation cytotoxicity in
      human prostate cancer.
AB  - The purpose of the present study was to determine the therapeutic potential of
      combining radiotherapy with tumor necrosis factor (TNF)-alpha-based gene therapy
      in the human prostate cancer PC-3 xenograft. PC-3 cells are highly resistant to
      TNF-alpha-induced cytotoxicity in vitro. A modest enhancement of radiation
      killing was observed with the addition of TNF-alpha in clonogenic survival
      assays. Combined treatment with Ad.Egr-TNF, a replication-deficient adenovirus
      modified to express TNF-alpha following the exposure of infected cells to
      ionizing radiation (40 Gy administered at 5 Gy per fraction) in vivo, resulted in
      increased tumor control, as defined by a reduction of tumor volume, when compared
      with treatment with Ad.Egr-TNF alone or with radiation alone (P < .03). The
      improvement in tumor control was achieved without increasing acute normal tissue
      damage when compared with tissue injury from radiation alone. The results of
      these studies support further development and clinical application of genetic
      radiotherapy for human prostate cancer.

PMID- 9917089
TI  - Gene transfer into human dendritic antigen-presenting cells by vaccinia virus and
      adenovirus vectors.
AB  - In a search for means to deliver exogenous gene(s) into human dendritic cells
      (DCs) from the perspective of tumor-specific vaccination, we have evaluated two
      recombinant viruses, both of which carry a reporter gene which is namely a
      modified vaccinia virus Ankara (MVA) and an adenovirus, as possible expression
      vectors. The recombinant MVA-P11 LZ vector carries the Escherichia coli lacZ gene
      coding for the enzyme beta-galactosidase, and the recombinant Ad-MFG-AP vector
      carries a modified membrane-exposed alkaline phosphatase (AP) gene. DCs were
      generated ex vivo in the presence of tumor necrosis factor-alpha, granulocyte
      macrophage colony-stimulating factor, stem cell factor, and flk-2/flt-3 ligand
      taken from CD34+ hematopoietic progenitors that were mobilized into the
      peripheral blood of cancer patients treated with high-dose cyclophosphamide and
      filgrastim. The target cells used for gene delivery were either CD34+ cells that
      had been subsequently induced to differentiate into mature DCs or DCs transduced
      after ex vivo generation from CD34+ cells. The results showed that: (a) infection
      of CD34+ cell derived-DCs (mature DCs) with either viral vector resulted in the
      efficient synthesis of recombinant protein, and (b) CD34+ cells were permissive
      for the expression of the recombinant reporter gene after infection with Ad-MFG
      AP but not after infection with MVA-P11 LZ. In conclusion, these results suggest
      that vaccinia and adenovirus vectors are candidate to act as vehicles in
      genetically engineering human DCs.

PMID- 9917090
TI  - Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth
      factor receptor antibodies: improved immunogene approach.
AB  - We previously developed the "immunogene" approach toward cancer gene therapy
      using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we
      describe an improved immunogene system, in which the antigen-binding (Fab)
      fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were
      conjugated with poly-L-lysine to form a gene delivery vehicle (designated Fab
      "immunoporter"). Within 12 hours, the beta-galactosidase beta-gal) gene was
      transferred via the Fab immunoporter to virtually all of the nuclei of human
      squamous carcinoma A431 cells that overproduce the EGFR, and the beta-gal enzyme
      activity was detected within 24 hours and retained for more than 3 days. The beta
      gal gene was not transferred into human and mouse cells that were deficient in
      EGFRs, but it was delivered if those mouse cells were transformed with human EGFR
      genes. Beta-gal gene transfer via the Fab immunoporter was inhibited by
      pretreatment with excess amounts of the Fab fragment. The transfer efficiency of
      the beta-gal gene to A431 cells via the Fab immunoporter was approximately 2%,
      which is as high as the lipofection method and 20- to 100-fold higher than the
      whole Ab immunoporter. The transfer of the herpes simplex virus thymidine kinase
      gene into A431 tumor cells as a form of the thymidine kinase/Fab immunogene was
      successful, and subsequent treatment with ganciclovir induced remarkable suicide
      effects which conferred 1000-fold higher drug sensitivity. Thus, the Fab
      immunogene was substantially improved with regard to the whole Ab immunogene and
      could be used as a potent gene transfer vehicle for the in vivo targeting of EGFR
      hyperproducing tumor cells.

PMID- 9917091
TI  - Distribution, persistency, toxicity, and lack of replication of an E1A-deficient
      adenoviral vector after intracardiac delivery in the cotton rat.
AB  - Adenoviral vectors were inoculated via intracardiac injection into 5- to 1O-week
      old cotton rats (Sigmodon hispidus) to evaluate the effects of systemic delivery.
      Cotton rats were chosen as a model because they are semipermissive to the
      replication of human adenoviruses. The vector used was AdV.RSV-tk, a replication
      deficient adenovirus with a herpes simplex virus thymidine kinase gene inserted
      in the E1 region. Vector doses were 3 x 10(8), 3 x 10(9), and 3 x 10(10) viral
      particles per animal with and without ganciclovir at 10 mg/kg twice a day.
      Animals were sacrificed and necropsied at 24 hours, 7 days, and 14 days
      postinoculation. Gross and microscopic pathologic observations in dosed groups
      were compared with an unmanipulated control group. From each animal, 10 different
      organ systems were analyzed for histopathology and vector distribution. The only
      significant microscopic lesions observed were epicardial inflammation and splenic
      hemosiderosis. Vector sequences persisted throughout the 14-day assay with
      preponderance in the heart, lung, and lymphoid organs. Infectious virions were
      detected for 24 hours, and these virions were only detected at the site of
      injection of two animals in the highest dose group. No viral replication was
      detected. Therefore, systemic delivery of up to 3 x 10(11) viral particles/kg was
      well tolerated in this semipermissive host model and did not result in any
      significant pathology.

PMID- 9917092
TI  - Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor
      necrosis factor (TNF)-alpha induces significant tumor regression.
AB  - Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo
      gene delivery. VKCK is a murine myeloma cell line expressing the light chain of
      the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro
      transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene
      beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of
      1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units)
      resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV
      pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the
      heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro
      transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000,
      transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36
      ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture.
      The secretion peaks at day 3 and is diminished at day 6 following the viral
      infection. These transfected VKCK cells also became more immunogenic with
      enhanced expression of major histocompatibility complex class I antigen.
      Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha
      virus with a repeated booster resulted in significant VKCK tumor regression in
      immune-competent mice, but not in athymic nude mice with a mean tumor weight of
      0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with
      AdV5LacZ and phosphate-buffered saline, respectively (P < .01). The tumor
      regression also results in protective immunity against a second challenge with
      parental tumor cells, which is mainly mediated by VKCK tumor-specific CD8+ T
      cells. These results indicate that AdV-mediated cytokine gene therapy may be a
      useful approach in the clinical management of solid human tumors.

PMID- 9917093
TI  - Dendritic cells augment granulocyte-macrophage colony-stimulating factor (GM
      CSF)/herpes simplex virus thymidine kinase-mediated gene therapy of lung cancer.
AB  - Lung cancer, the leading cause of cancer death in the United States, is resistant
      to most currently available therapies. To evaluate a multicomponent gene therapy
      approach that replaces tumor-bearing host immune deficits, we genetically
      modified Line 1 (L1C2), a weakly immunogenic alveolar cell carcinoma cell line.
      L1C2 was transduced ex vivo with a retroviral construct that contained two
      components: a cytokine gene (granulocyte-macrophage colony-stimulating factor)
      and a drug sensitivity gene (herpes simplex virus thymidine kinase). The third
      component of this therapy, in vitro-activated syngeneic bone marrow-derived
      dendritic cells, was included to augment antigen presentation. The addition of
      ganciclovir (GCV) caused the lysis of transduced tumor cells, resulting in the
      release of potential tumor antigens. Ex vivo-transduced tumor cells regressed in
      vivo following GCV therapy but were not effective in the treatment of established
      parental tumors. To treat established tumors, dendritic cells were administered
      in combination with transduced tumor cells and GCV. A total of 50% of these mice
      rejected the 5-day-old established tumors and were immune to rechallenge with
      parental L1C2 cells. Thus, this multicomponent gene therapy system leads to both
      the regression of established tumors and enhanced immunogenicity in this weakly
      immunogenic murine lung cancer model.

PMID- 9917094
TI  - Retroviral vector-mediated transfer of the interferon-alpha gene in chronic
      myeloid leukemia cells.
AB  - The transfer and expression of cytokine genes into tumor cells is reportedly a
      valuable approach to improve the antitumor activity of cytokines in various
      models. Interferon (IFN)-alpha may induce hematological remission in chronic
      myeloid leukemia (CML) patients, but only a small proportion of patients achieve
      a sustained, complete cytogenetic remission. We have investigated the possibility
      of transducing CML cells with the retroviral vector LIalpha2SN, which encodes the
      IFN-alpha2 gene. We first optimized the transduction efficiency using the CML
      derived K562 cell line. A transduction efficiency of 50% and 85% after three and
      six infections, respectively, was obtained in K562 cells. We then expressed IFN
      alpha2 in CML cells by transducing the latter with LIalpha2SN viral particles.
      The IFN-alpha secretion after three and six infections was 5,400 and 18,000 U/24
      hours/10(6) cells for unselected K562 cells and 7,000 and 290 U/24 hours/10(6)
      cells for CML CD34+ cells at days 4 and 5. Moreover, the major histocompatibility
      complex class I antigens were overexpressed after infection with LIalpha2SN in
      both K562 and CML CD34+ cells. The proliferation (in liquid culture) and the
      cloning efficiency of these CML cells were significantly decreased after
      LIalpha2SN treatment. By contrast, the proliferation of cord blood CD34+ cells
      was not affected by transduction with LIalpha2SN. These results demonstrate the
      transduction efficiency of CML cells and suggest the possibility of CML cell
      immunotherapy with retroviral gene transfer of different cytokines such as IFN
      alpha.

PMID- 9917095
TI  - Transfer of chimeric receptor gene made of variable regions of tumor-specific
      antibody confers anticarbohydrate specificity on T cells.
AB  - The antitumor specificity of T cells can be induced by gene transfer using a
      recently developed therapeutic approach (T body). In this work, we genetically
      conferred anticarbohydrate specificity onto T cells using the variable regions of
      monoclonal antibody MLuC1, which binds the Lewis(Y) (LeY) tumor-associated
      antigen that is overexpressed on several human carcinomas. The variable regions
      of MLuC1, which are in a single-chain Fv (ScFv) configuration, were cloned and
      spliced in a eukaryotic expression vector with both the gene encoding the signal
      transducing gamma-chain of the human Fcgamma receptor and a flexible hinge
      domain. The chimeric ScFv-gamma gene was expressed in a murine cytotoxic T-cell
      hybridoma. Transfectants receiving vector only served as a negative control
      (mock). Screening for functional transfectants was carried out using a tumor
      growth inhibition assay. The soluble form of MLuC1 ScFv was recovered from
      bacteria periplasm and tested for binding to LeY-expressing cells by the
      fluorescence-activated cell sorter analysis. Despite the low binding ability of
      the soluble MLuC1 ScFv, 7 of 13 genetically engineered cytotoxic T lymphocyte
      clones inhibited the growth of LeY-positive cells and did not affect growth of
      LeY-negative cells. None of the mock clones tested specifically inhibited tumor
      growth. These data indicate that, by chimeric MLuC1 ScFv-gamma gene transfer, it
      is possible to confer anticarbohydrate specificity onto T cells and extend the
      applicability of the T-body approach to tumor-associated antigens that are
      naturally not recognized by T cells.

PMID- 9917096
TI  - Gene therapy using antisense oligodeoxynucleotides labeled with Auger-emitting
      radionuclides.
AB  - Antisense oligomers may be used as a vehicle for carrying a radiation source into
      a specific location inside a tumor cell. The effects of radioactive-labeled
      oligodeoxynucleotides (ODNs) may have both direct antisense inhibition and
      radiation. Thus far, the use of radioactive ODNs has been limited mostly to
      clinical biokinetic studies. Therapeutic possibilities remain unknown if the
      basic question of the optimal source of radiation is unanswered. We have shown
      previously that oligonucleotide therapy can be effective theoretically with the
      internally labeled ODN phosphorothioates 32P, 33P, and 35S. Here, we expand the
      selection of radionuclides; we calculated in vivo subcellular tissue distribution
      for ODN phosphorothioates using the decay characteristics of several beta- and
      Auger-emitting radionuclides: 32P, 35S, 51Cr, 67Ga, 111In, (1114m)In, 123I, 125I,
      131I, and 201Tl. The absorbed nuclear doses of these radiolabeled
      oligonucleotides were estimated in different cellular dimensions using the
      subcellular biodistribution data for two oligonucleotides (ISIS 2105 and ISIS
      2922). Our results indicate that Auger-emitter isotopes do not give higher
      absorbed cell nuclear doses than the isotopes suitable for internal labeling of
      ODN phosphorothioates. However, the biological difference is difficult to
      estimate. The best isotope for subcellular targeting was 35S, which gives the
      smallest variation of nuclear dose in the different cell dimensions we studied
      (nuclear diameter, 6-16 microm; cellular diameter, 12-20 microm). Therefore, we
      conclude that in oligonucleotide radiotherapy, nuclear targets should be treated
      with short-range beta-emitters (35S or 33P) that are suitable for the internal
      labeling of oligonucleotides unless the relative biological effectiveness of
      Auger-emitters could be remarkably improved. Dual labeling with 32P and 35S may
      provide therapeutic benefits when treating smaller and larger targets
      simultaneously. Further in vivo development, especially with 33P and 35S labels
      for ODNs, is strongly indicated.

PMID- 9917097
TI  - A piece of my mind. Too sad.

PMID- 9917098
TI  - Advances in the treatment of hypertension.

PMID- 9917099
TI  - Chlamydial infections and the risk of ectopic pregnancy.

PMID- 9917100
TI  - New method to repair faulty genes stirs interest in chimeraplasty technique.

PMID- 9917101
TI  - Switch to human insulin worries some diabetics.

PMID- 9917102
TI  - A thought for your pennies.

PMID- 9917103
TI  - From the Centers for Disease Control and Prevention. Hypothermia-related deaths-
      Georgia, January 1996-December 1997, and United States, 1979-1995.

PMID- 9917104
TI  - From the Centers for Disease Control and Prevention. Outbreak of primary and
      secondary syphilis--Guilford County, North Carolina, 1996-1997.

PMID- 9917105
TI  - From the Centers for Disease Control and Prevention. Update: respiratory
      syncytial virus activity--United States, 1997-98 season.

PMID- 9917106
TI  - From the Centers for Disease Control and Prevention. Impact of closure of a
      sexually transmitted disease clinic on public health surveillance of sexually
      transmitted diseases--Washington, D.C., 1995.

PMID- 9917107
TI  - Nevirapine, didanosine, and zidovudine for patients with HIV: the INCAS trial.
      Italy, Netherlands, Canada, and Australia.

PMID- 9917108
TI  - Nevirapine, didanosine, and zidovudine for patients with HIV: the INCAS trial.
      Italy, Netherlands, Canada, and Australia.

PMID- 9917109
TI  - Nevirapine, didanosine, and zidovudine for patients with HIV: the INCAS trial.
      Italy, Netherlands, Canada, and Australia.

PMID- 9917110
TI  - Beta-blockers as first-line agents for hypertension in the elderly.

PMID- 9917111
TI  - Talking with patients about screening for prostate cancer.

PMID- 9917112
TI  - Reducing sleepiness on the roads and on the wards.

PMID- 9917113
TI  - Reducing sleepiness on the roads and on the wards.

PMID- 9917114
TI  - Public performance reports for cardiac surgery.

PMID- 9917115
TI  - Academic and legal aspects of authorship disputes.

PMID- 9917116
TI  - Efficacy and safety of lovastatin in adolescent males with heterozygous familial
      hypercholesterolemia: a randomized controlled trial.
AB  - CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder
      associated with early coronary artery disease, especially in men. The age at
      which drug therapy should be started is still controversial, as is the use of 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To
      assess the lipid-lowering efficacy, biochemical safety, and effect on growth and
      sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year,
      double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In
      the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the
      dosage remained stable during the second period (24 weeks). The study was
      conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics
      in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH.
      Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention,
      59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second
      periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a
      forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo.
      MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density
      lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual
      development. RESULTS: Compared with placebo, LDL-C levels of patients receiving
      lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving
      dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than
      baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and
      testicular volume were not significantly different between the lovastatin and
      placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum
      hormone levels or biochemical parameters of nutrition. However, the study was
      underpowered to detect significant differences in safety parameters. Serum
      vitamin E levels were reduced with lovastatin treatment consistent with
      reductions in LDL-C, the major carrier of vitamin E in the circulation.
      CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing
      effectiveness of lovastatin. Comprehensive clinical and biochemical data on
      growth, hormonal, and nutritional status indicated no significant differences
      between lovastatin and placebo over 48 weeks, although further study is required.

PMID- 9917117
TI  - A structured teaching and self-management program for patients receiving oral
      anticoagulation: a randomized controlled trial. Working Group for the Study of
      Patient Self-Management of Oral Anticoagulation.
AB  - CONTEXT: Control of oral anticoagulation therapy has been reported to often be
      inadequate. Previous retrospective investigations suggest that patients' self
      adjustment of oral anticoagulants may lead to improved control. OBJECTIVE: To
      investigate the effects of patients' self-management of oral anticoagulation
      therapy on accuracy of control and measures of treatment-related quality of life.
      DESIGN: Randomized, single-blind, multicenter trial. SETTING AND PARTICIPANTS: A
      total of 179 patients receiving long-term oral anticoagulation treatment were
      enrolled at 5 referral centers in Germany. INTERVENTION: Patients were randomized
      to an oral anticoagulation self-management group based on a structured treatment
      and teaching program and international normalized ratio (INR) self-monitoring.
      The control group received conventional care as provided by family physicians,
      including referral to specialists if necessary. MAIN OUTCOME MEASURES: Deviation
      of INR values from the individual INR target range (squared) and the 5 categories
      of treatment-related quality of life. RESULTS: Deviation of INR value from the
      mean of the INR target range was significantly lower in the intervention group at
      3-month (squared INR deviation, 0.59 vs 0.95; P<.001) and 6-month follow-up (0.65
      vs 0.83; P=.03) compared with the control group. Also, the intervention group had
      INR values within the target range more often (repeated measurement analysis for
      categorical data, P=.006). The results were mainly due to less frequent
      suboptimal INR values in the intervention group (32.8% vs 50.0% [P=.03] at 3
      month, and 33.7% vs 48.2% [P=.08] at 6-month follow-up). Treatment-related
      quality-of-life measures, especially treatment satisfaction scores, were
      significantly higher in the intervention group compared with controls.
      CONCLUSIONS: An anticoagulation education program that includes self-management
      of anticoagulation therapy results in improved accuracy of anticoagulation
      control and in treatment-related quality-of-life measures. Further studies are
      needed to describe whether the program will reduce risk of bleeding or
      thromboembolism.

PMID- 9917118
TI  - Lack of long-term effects of in utero exposure to zidovudine among uninfected
      children born to HIV-infected women. Pediatric AIDS Clinical Trials Group
      Protocol 219/076 Teams.
AB  - CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of
      perinatal transmission of the human immunodeficiency virus (HIV), an increasing
      number of HIV-exposed but uninfected children will have in utero exposure to
      zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term
      effects of in utero exposure to zidovudine vs placebo among a randomized cohort
      of uninfected children. DESIGN: Prospective cohort study based on data collected
      during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine
      HIV prevention trial, and Protocol 219, a long-term observational protocol.
      SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred
      thirty-four uninfected children born to 230 HIV-infected women enrolled in
      Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in
      the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES:
      Physical growth measurements, immunologic parameters, cognitive/developmental
      function, occurrence of neoplasms, and mortality data assessed every 6 months for
      children younger than 24 months and yearly thereafter or as clinically indicated.
      Baseline echocardiogram and funduscopic evaluations were collected before 36
      months of age. RESULTS: Median age of children at time of last follow-up visit
      was 4.2 years (range, 3.2-5.6 years). There were no significant differences
      between children exposed to zidovudine and those who received placebo in terms of
      sequential data on lymphocyte subsets; weight, height, and head circumference z
      scores; and cognitive/developmental function. No deaths or malignancies occurred.
      Two children (both exposed to zidovudine) are being followed up for abnormal,
      unexplained ophthalmic findings. One child exposed to zidovudine had a mild
      cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically
      asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected
      children with in utero and neonatal exposure to zidovudine followed up for as
      long as 5.6 years. Continued prospective evaluations of children born to HIV
      infected women who are exposed to antiretroviral or immunotherapeutic agents are
      critical to assess the long-term safety of interventions that prevent perinatal
      HIV transmission.

PMID- 9917119
TI  - Multinational outbreak of Salmonella enterica serotype Newport infections due to
      contaminated alfalfa sprouts.
AB  - CONTEXT: In December 1995, reported Salmonella enterica serotype Newport (SN)
      infections increased sharply in Oregon and British Columbia but not elsewhere in
      North America. Similar unexplained increases had been noted in 6 other states in
      the fall of 1995. OBJECTIVE: To determine the source of the outbreak(s). DESIGN:
      Case-control studies, environmental investigations, bacterial subtyping, and
      surveillance information review. SETTINGS: Oregon and British Columbia
      communities (winter 1995-1996) and Georgia, Oklahoma, Pennsylvania, Vermont,
      Virginia, and West Virginia (fall 1995). PARTICIPANTS: Oregon and British
      Columbia residents with culture-confirmed SN infections and onset from December
      1, 1995, through February 29, 1996, and healthy community controls. MAIN OUTCOME
      MEASURES: Odds ratio (OR) of illness associated with exposures; distribution
      patterns and culture of alfalfa seeds and sprouts; subtyping of SN isolates.
      RESULTS: We identified 133 cases in Oregon and British Columbia; 124 (93%)
      occurred in patients older than 18 years; 87 (65%) were female. Case patients
      were more likely than community control subjects to report having eaten alfalfa
      sprouts in the 5 days preceding illness (41% [17/41] vs 4% [3/75]; OR, 17.0; 95%
      confidence interval, 4.3-96.0). Case isolates shared a distinctive pulsed-field
      gel electrophoresis (PFGE) pattern. The SN was grown from seeds and alfalfa
      sprouts. The distribution of 1 seed lot to multiple growers corresponded to the
      distribution of cases. Distribution of a second seed lot from the same European
      wholesaler corresponded to the location of the fall outbreak, which was
      characterized by a similar demographic profile. The PFGE pattern of fall outbreak
      isolates and confiscated sprouts and seeds was indistinguishable from the Oregon
      and British Columbia outbreak and differed from background isolates. CONCLUSIONS:
      The SN-contaminated alfalfa seeds were distributed to multiple growers across
      North America in 1995 and resulted in a protracted international outbreak
      scattered over many months. Current sprouting methods are inadequate to protect
      consumers from such events. Alfalfa sprouts may be an elusive but important
      vehicle for salmonellosis and other enteric infections.

PMID- 9917120
TI  - Quality end-of-life care: patients' perspectives.
AB  - CONTEXT: Quality end-of-life care is increasingly recognized as an ethical
      obligation of health care providers, both clinicians and organizations. However,
      this concept has not been examined from the perspective of patients. OBJECTIVE:
      To identify and describe elements of quality end-of-life care from the patient's
      perspective. DESIGN: Qualitative study using in-depth, open-ended, face-to-face
      interviews and content analysis. SETTING: Toronto, Ontario. PARTICIPANTS: A total
      of 126 participants from 3 patient groups: dialysis patients (n = 48), people
      with human immunodeficiency virus infection (n = 40), and residents of a long
      term care facility (n = 38). OUTCOME MEASURES: Participants' views on end-of-life
      issues. RESULTS: Participants identified 5 domains of quality end-of-life care:
      receiving adequate pain and symptom management, avoiding inappropriate
      prolongation of dying, achieving a sense of control, relieving burden, and
      strengthening relationships with loved ones. CONCLUSION: These domains, which
      characterize patients' perspectives on end-of-life care, can serve as focal
      points for improving the quality of end-of-life care.

PMID- 9917121
TI  - Comparable specificity of 2 commercial tuberculin reagents in persons at low risk
      for tuberculous infection.
AB  - CONTEXT: One or both commercial tuberculin skin test reagents (Aplisol and
      Tubersol) may have a high rate of false-positive reactions. OBJECTIVE: To compare
      the reaction size and specificity of skin testing with Aplisol, Tubersol, and the
      standard purified protein derivative (PPD-S1). DESIGN: Double-blind trial,
      conducted between May 14, 1997, and October28, 1997, in which each individual
      received 4 tuberculin skin reagents at sites assigned at random. SETTING: Health
      departments and universities in 6 US cities. PARTICIPANTS: A total of 1555
      persons at low risk of latent tuberculosis infection. INTERVENTION: Simultaneous
      skin tests with Aplisol, Tubersol, PPD-S1, and either a second PPD-S1 or PPD-S2
      (a proposed new standard). MAIN OUTCOME MEASURE: Reaction size at each injection
      site measured by 2 investigators blinded to type of reagent. RESULTS: Aplisol
      produced slightly larger reactions than Tubersol, but this difference did not
      significantly change skin test interpretation. The mean +/- SD reaction sizes
      were 3.4+/-4.2 mm with Aplisol, 2.1+/-3.2 mm with Tubersol, and 2.5+/-3.6 mm with
      PPD-S1. Assuming that all participants were uninfected and using a 10-mm cutoff,
      the specificities of the tests were high: Aplisol, 98.2%; Tubersol, 99.2%; and
      PPD-S1, 98.9%. Significant variability was not detected in interobserver, host,
      and lot-to-lot reagent comparisons. CONCLUSION: Using a cutoff of at least 10 mm,
      testing with 3 different PPD reagents resulted in similar numbers of uninfected
      persons being correctly classified.

PMID- 9917123
TI  - When should patients with heterozygous familial hypercholesterolemia be treated?

PMID- 9917122
TI  - Management of ventricular arrhythmias: detection, drugs, and devices.
AB  - OBJECTIVE: To review evaluation and treatment of patients with ventricular
      arrhythmias, based on recent studies, with an emphasis on randomized controlled
      trials. DATA SOURCES: MEDLINE search of English-language publications of
      ventricular arrhythmias and their references from 1966 through April 27, 1998.
      References to articles were also scanned to broaden the search. STUDY SELECTION:
      Randomized controlled trials and all large nonrandomized trials of arrhythmias
      and arrhythmia therapy were reviewed. In addition, studies that led to changes in
      approach to patients with arrhythmias were reviewed. DATA EXTRACTION: We reviewed
      articles jointly for pertinent studies and information. DATA SYNTHESIS: The goals
      of treatment of the patient with ventricular arrhythmias are to suppress symptoms
      and prevent a fatal event. The steps in providing such therapy include defining
      the cardiac anatomy, assessing arrhythmia risk through noninvasive or invasive
      testing, and prescribing treatment based on these results. Patients may be
      separated into high- and low-risk groups to help identify appropriate treatment.
      While low-risk groups may benefit from reassurance or medications such as beta
      blockers or verapamil, high-risk groups have been more difficult to treat. Recent
      randomized trials of implantable cardioverter defibrillators for ventricular
      arrhythmias suggest that they may provide better protection for high-risk
      patients than do antiarrhythmic medications. CONCLUSIONS: Treatment and
      understanding of risk from ventricular arrhythmias have advanced substantially in
      recent years. Classifying patients as being at high or low risk for fatal
      arrhythmias allows the physician to identify appropriate treatments for the high
      risk patient without exposing the low-risk patient to unnecessary treatment
      related risks.

PMID- 9917124
TI  - Empowering patients to monitor and manage oral anticoagulation therapy.

PMID- 9917126
TI  - JAMA patient page: cholesterol.

PMID- 9917125
TI  - Childhood malnutrition and postwar reconstruction in rural El Salvador: a
      community-based survey.
AB  - CONTEXT: The 1992 peace settlement that ended the civil war in El Salvador
      included land redistribution and other provisions designed to improve the
      socioeconomic status of ex-combatants and vulnerable civilians. OBJECTIVE: To
      describe associations between postwar social and economic assistance programs,
      especially land reform, and current child health status as reflected by nutrition
      in a population of resettled rural refugees. DESIGN: A population-based cross
      sectional survey of child nutritional status and principal elements of the
      reconstruction process. SETTING: A single rural municipality in northern El
      Salvador. PARTICIPANTS: A representative sample of 761 children younger than 5
      years, living in 27 villages. MAIN OUTCOME MEASURE: Prevalence of stunting (low
      height for age) in children younger than 5 years. RESULTS: Prevalence of stunting
      was 32.4%. Stunting was significantly more prevalent among children whose
      families cultivated less land (odds ratio [OR] for stunting per additional
      hectare of redistributed land cultivated, 0.64; 95% confidence interval [CI],
      0.44-0.93). Less than half of newly transferred land was being cultivated by its
      owners. Most of the children (84.7%) lived in families cultivating 2 hectares or
      less of redistributed land. Stunting was also more prevalent among children whose
      households lacked piped water (adjusted OR, 2.72; 95% CI, 1.87-3.96) vs those who
      had had piped water since before the cease-fire. CONCLUSIONS: Malnutrition,
      particularly stunting, persisted at high levels and was strongly associated with
      delay in full cultivation of redistributed land and in provision of water.

PMID- 9917127
TI  - Molecular pathology and managed care: challenges and opportunities.
AB  - The inherent costs of sophisticated molecular-based diagnostic tests are of
      significant importance to managed care organizations. Providers of molecular
      diagnostic services have emphasized that these tests can provide a reduced length
      of stay for hospitalized patients resulting from earlier definitive diagnosis, a
      reduction in the use of less expensive nondefinitive tests, a reduction in
      expensive ancillary diagnostic services such as radiologic imaging and
      endoscopies, an enhanced ability to predict disease outcome and responses to
      various expensive therapies, and new programs in detecting disease risk and
      maintaining patient wellness. In order for these newer molecular-based tests to
      be included in the list of covered services by the health maintenance
      organizations (HMOs), the clinical value and potential cost-benefit ratios must
      be articulated to the medical directors, administrative officials, and
      subscribers of the HMOs by the molecular diagnostic test providers.

PMID- 9917128
TI  - U.S. Senate Bill 422: the Genetic Confidentiality and Nondiscrimination Act of
      1997.
AB  - On March 11, 1997, Senator Pete Domenici introduced U.S. Senate Bill 422, the
      Genetic Confidentiality and Non-Discrimination Act of 1997. The bill specifies
      that "existing legal protections for genetic information are inadequate to ensure
      genetic privacy and to prevent genetic discrimination." The first stated purpose
      of the bill is "to define the circumstances under which DNA samples may be
      collected, stored, and analyzed and genetic information may be collected, stored,
      analyzed, and disclosed." The bill reinforces statutes already passed in 19
      states that guarantee patients certain rights of control over their own personal
      genetic information (Congressional Record, S2141). This bill fundamentally
      changes the mechanism whereby molecular biologists acquire tissue, and defines
      new obligations between researchers and human subjects. Even if this bill is not
      passed in its present form, it appears inevitable that legislation with a similar
      intent will soon emerge. Any such legislation will carry the full weight and
      penalties of law. Because many current research practices may violate these
      proposed new regulations, researchers should understand the provisions of S. 422.
      Furthermore, it is crucial that researchers understand the bill now, before it
      becomes law, because this may be their last opportunity to lobby for any
      modifications of the bill.

PMID- 9917129
TI  - Genotypic analysis of flow-sorted and microdissected head and neck squamous
      lesions by whole-genome amplification.
AB  - To investigate the utility of primer extension preamplification (PEP) in the
      genetic analysis of head and neck squamous tumorigenesis, microsatellite analysis
      was performed on matched deoxyribonucleic acid (DNA) samples extracted from 32
      flow-sorted and microdissected specimens before and after PEP. Eighteen fresh and
      nine archival specimens were taken from invasive carcinomas, and five specimens
      were obtained from microdissected archival premalignant squamous epithelial
      lesions. Identical microsatellite patterns were observed in 276 (87%) of the 319
      paired PEP and non-PEP genotypes with sufficient DNA. Overall, 13 (4%) of the PEP
      and 28 (8.8%) of the non-PEP fresh tissue samples failed specific microsatellite
      amplification. All 14 PEP-archival specimens were successfully amplified. Sorted
      cells showed a higher incidence (42.8%) of loss of heterozygosity (LOH) in both
      PEP and non-PEP samples compared with their unsorted counterparts. The results of
      this study indicate that (a) PEP is a simple and reliable technique for enhancing
      the DNA yield from small specimens; (b) flow sorting, in certain cases, improves
      the interpretation of genetic results; and (c) PEP may be used to compensate for
      PCR failure of unamplified DNA specimens in these lesions.

PMID- 9917130
TI  - RNA from decades-old archival tissue blocks for retrospective studies.
AB  - The validity of molecular studies using DNA and RNA extracted from decades-old
      formalin-fixed and paraffin-embedded tissue blocks has been demonstrated. The
      quality and usability of DNA and RNA from archival tissues are modified by
      various factors, such as the fixative, the fixation time, and the postmortem
      time. However, in contrast to DNA, there are no comprehensive studies
      quantitatively addressing the feasibility of RNA from old (more than 10 years)
      archival samples. This study examined the integrity of RNA extracted from 738
      autopsy liver and 63 autopsy thyroid cancer tissue blocks procured during a span
      of nearly four decades, beginning in 1952 and ending in 1989, from the atomic
      bomb survivors. The integrity of RNA was assessed by amplification of c-BCR
      messenger RNA (mRNA) between two sequential exons with an intervening intron by
      reverse-transcription polymerase chain reaction (RT-PCR). The integrity of RNA
      was influenced by the age of the samples and the postmortem time, but not by the
      formalin-fixation period. It was possible to amplify more than 60% of the
      samples. Using these RNAs, the HCV genome in liver cancers and the H4-RET gene in
      thyroid cancers were detectable. This study illustrates the possibility of
      molecular studies using RNA from routinely prepared paraffin blocks stored for
      long periods and provides the statistics and critical factors to consider in
      assessing the feasibility of such contemplated studies.

PMID- 9917131
TI  - Molecular methods for detecting t(11;14) translocations in mantle-cell lymphomas.
AB  - The t(11;14)(q13;q32) and its molecular counterpart, bcl1/JH, are characteristic
      of mantle-cell lymphomas (MCL). Molecular detection of the translocation is
      useful in diagnosis and classification, and also shows promise in detecting
      minimal residual disease. The purpose of this study was to determine the
      frequency of detecting bcl1/JH by polymerase chain reaction (PCR) compared with
      Southern blot analysis in cases proven by cytogenetic analysis to harbor
      t(11;14). Southern blot analysis using two probes targeting the major
      translocation cluster (MTC) and a third probe targeting the p94 region was
      performed, along with PCR using two different bcl1 MTC primers, on 18 cases of
      MCL known to have t(11;14). Southern blot analysis revealed bcl1 rearrangement in
      13 of 18 cases (72%), 12 with MTC breakpoints and 1 with a p94 breakpoint. The
      2.1-kb MTC probe "b" was superior to the smaller 700-bp probe "a" in detecting
      these rearrangements. The MTC translocation was identified by PCR in 10 of 12
      cases, and both primer sets that were tested performed equally well. This study
      illustrates the frequency with which molecular methods detect known t(11;14)
      translocations in MCLs. These results may help clinical laboratory scientists
      optimize their procedure for detecting bcl1 translocations by molecular methods
      at initial diagnosis and for purposes of detecting minimal residual disease.

PMID- 9917132
TI  - Association of p53 accumulation with TP53 mutations, loss of heterozygosity at
      17p13, and DNA ploidy status in 273 colorectal carcinomas.
AB  - The aim of this study was to establish an experimentally based cutoff level for
      assessing p53 immunoreactivity in colorectal tumors. The accumulation of p53
      protein in 273 colorectal tumors was correlated with previously obtained data on
      TP53 mutation and loss of heterozygosity at two 17p13 loci in the same tumors.
      The monoclonal antibody PAb 1801 was used for p53 staining, and the results
      obtained by immunohistochemistry and immunoblotting were similar. Mutation
      analyses of exons 5-8 were performed using constant denaturant gel
      electrophoresis followed by sequencing. There were no statistically significant
      differences for any measured TP53 gene alteration between the group of tumors
      without p53-positive nuclei (n = 83) and the group with <5% positive nuclei (n =
      58). The majority of mutations within these groups were deletions/insertions and
      nonsense mutations without p53 accumulation. Therefore, we assume that 5% p53
      positive nuclei is the relevant cutoff level to assess TP53 damage in colorectal
      tumors. A prerequisite for this recommendation is optimal conditions for p53
      protein detection. The parameters for p53 dysfunction were correlated to DNA
      aneuploidy measured by flow cytometry. TP53 mutations were significantly
      associated with DNA aneuploidy (P < 0.00001), and a nonrandom distribution of
      TP53 gene alterations among diploid (DI = 1), hyperdiploid (1.0 < DI < 1.3), and
      highly aneuploid (DI > 1.3) tumors indicates that DNA hyperdiploid tumors
      constitute a separate developmental entity different from tumors with gross
      aneuploidy.

PMID- 9917133
TI  - Deletion of the p16 gene and microsatellite instability in carcinoma arising in
      pleomorphic adenoma of the parotid gland.
AB  - Carcinoma arising in pleomorphic adenoma of the salivary gland is a rare tumor,
      and its molecular aspects are unknown. Recent studies have revealed that
      malignant transformation of various human cancers may involve two different
      genetic alterations: inactivation of the p16 gene, which is a putative tumor
      suppressor gene, and genetic instability represented by microsatellite
      instability (MSI). However, so far, molecular investigations including p16 gene
      alteration and MSI have not been performed on carcinoma arising in pleomorphic
      adenoma. Both inactivation of the p16 gene and MSI were studied using DNA
      extracted from paraffin-embedded sections of carcinoma arising in pleomorphic
      adenoma. Samples also were analyzed for cyclin D1 gene amplification, which is
      thought to have oncogenic effects similar to those with inactivation of the p16
      gene. One case showed the homozygous deletion of the p16 gene in the carcinoma,
      although hypermethylation of the p16 gene and amplification of the cyclin D1 gene
      were not observed in any cases. In two of four cases, MSI was observed. One case
      in two showed MSI in both the pleomorphic adenoma and the carcinoma. Results of
      this study suggest that two different genetic alterations, the inactivation of
      the p16 gene and genetic instability, play roles in the malignant transformation
      of carcinoma in pleomorphic adenoma. The MSI observed in the adenoma suggests
      that genetic alterations occur in pleomorphic adenoma.

PMID- 9917135
TI  - Biosensors '98. Proceedings of the 5th World Congress on Biosensors. Berlin,
      Germany, 3-5 June 1998.

PMID- 9917134
TI  - Morpho-immunophenotypic-genotypic infidelity in synovial sarcoma.

PMID- 9917137
TI  - Myocardial response to disease, hormones and training. Proceedings of the XII
      Paavo Nurmi Symposium. Porvoo, Finland, June 1997.

PMID- 9917136
TI  - Mechanistic action of pediocin and nisin: recent progress and unresolved
      questions.
AB  - Nisin and pediocin PA-1 are examples of bacteriocins from lactic acid bacteria
      (LAB) that have found practical applications as food preservatives. Like other
      natural antimicrobial peptides, LAB bacteriocins act primarily at the cytoplasmic
      membranes of susceptible microorganisms. Studies with in vivo as well as in vitro
      membrane systems are directed toward understanding how bacteriocins interact with
      membranes so as to provide a mechanistic basis for their rational applications.
      The dissipation of proton motive force was identified early on as the common
      mechanism for the lethal activity of LAB bacteriocin. Models for nisin/membrane
      interactions propose that the peptide forms poration complexes in the membrane
      through a multistep process of binding, insertion, and pore formation. This
      review focuses on the current knowledge of: (1) the mechanistic action of nisin
      and pediocin-like bacteriocins, (2) the requirement for a cell factor such as a
      membrane protein, (3) the influence of membrane potential, pH, and lipid
      composition on the specificity and efficacy of bacteriocins, and (4) the roles of
      specific amino acids and structural domains of the bacteriocins in their action.

PMID- 9917138
TI  - Computer hardware resources on the internet.

PMID- 9917139
TI  - Tamoxifen and the uterus.

PMID- 9917140
TI  - The formation of the functional chorion structure of Drosophila virilis involves
      inercalation of the "middle" and "late" major chorion proteins: a general model
      for chorion assembly in Drosophilidae.
AB  - We have shown by in vitro development of staged follicles in the presence of
      tritiated proline, as well as by immunoblot analysis, that the Dvs19 and DVS15
      chorion proteins of Drosophila virilis are synthesized by the follicular
      epithelium and are incorporated in the chorion at the terminal stages of
      choriogenesis. Light microscopy immunolocalization has revealed that these two
      proteins represent structural components of the endochorion in all the
      specialized regions of the eggshell, while, contrary to their temporal pattern of
      secretion, electron microscopic immunolocalization has shown that these two
      proteins participate in endochorionic structures formed before the onset of their
      synthesis, thus suggesting an intercalation process during chorion formation.
      Furthermore, double immunolocalizations demonstrated that cosecreted proteins do
      not coexist in all secretory vesicles of the follicle cells, indicating that
      probably the final association of these chorionic components occurs
      extracellularly. On the basis of these data and those presented in the
      accompanying paper [Trougakos, I.P., and Margaritis, L.H. (1998)
      Immunolocalization of the temporally "early" secreted major structural chorion
      proteins, Dvs38 and Dvs36, in the eggshell layers and regions of Drosophila
      virilis, J. Struct. Biol. 123, 000-000.], a model for chorion assembly in
      Drosophilidae is proposed.

PMID- 9917141
TI  - Proceedings of the 2nd Symposium on Salivary Glands. Cagliari, Italy, May 23-25,
      1997. Dedicated to Niels Steensen (Niccolo Stenone).

PMID- 9917142
TI  - Dual publication.

PMID- 9917143
TI  - Assignment of 1H, 13C and 15N signals of the inhibitor protein Im9 bound to the
      DNase domain of colicin E9.

PMID- 9917144
TI  - Pros and cons of horizontal programs.

PMID- 9917145
TI  - Self-learning review. Hepatitis E.

PMID- 9917146
TI  - Hospital at home. For people with severe mental illness, results are encouraging.

PMID- 9917147
TI  - Hospital at home. Costings were inadequate.

PMID- 9917148
TI  - Acceptability of early discharge, hospital at home schemes. Care in community
      hospitals is another alternative.

PMID- 9917149
TI  - Deaths from low dose paracetamol poisoning. Guidelines are under review.

PMID- 9917150
TI  - Deaths from low dose paracetamol poisoning. Nomogram does not show absolute
      concentration for treatment.

PMID- 9917151
TI  - Deaths from low dose paracetamol poisoning. Several issues were not considered in
      the article.

PMID- 9917152
TI  - Deaths from low dose paracetamol poisoning. If in doubt use the antidote.

PMID- 9917153
TI  - Deaths from low dose paracetamol poisoning. Lower threshold has probably not
      overburdened hospital services in Gloucester.

PMID- 9917154
TI  - Deaths from low dose paracetamol poisoning. More evidence needed to change
      recommendations.

PMID- 9917155
TI  - Deaths from low dose paracetamol poisoning. Use of oral methionine for overdose
      below threshold for acetylcysteine.

PMID- 9917156
TI  - Limitation of over the counter sales of paracetamol. Restriction of 16g will not
      prevent overdose and is unhelpful for patients with chronic disease.

PMID- 9917157
TI  - Postnatal depression. Biology mustn't be excluded.

PMID- 9917158
TI  - Inequalities in health. Studies in inequality in health need careful
      interpretation.

PMID- 9917160
TI  - Underwater and Hyperbaric medicine, abstracts from the literature.

PMID- 9917159
TI  - The Bristol affair. GMC clarifies readers' misunderstandings.

PMID- 9917161
TI  - [Effect of geomagnetic field screening during orbital flight on expression of
      recombinant differentiation factor in escherichia coli cells].

PMID- 9917162
TI  - [Lipid peroxidation and indicators of antioxidant defence system in plasma and
      blood serum of rats during 14-day spaceflight on-board orbital laboratory
      "Spacelab-2"].

PMID- 9917163
TI  - [Donald Davis Flickenger-pioneer of bioastronautics].

PMID- 9917164
TI  - [History of aviation medicine in Poland].

PMID- 9917165
TI  - Hydrolysis and amino acid composition of proteins.
AB  - Amino acid composition analysis is a classical protein analysis method, which
      finds a wide application in medical and food science research and is
      indispensable for protein quantification. It is a complex technique, comprising
      two steps, hydrolysis of the substrate and chromatographic separation and
      detection of the residues. A properly performed hydrolysis is a prerequisite of a
      successful analysis. The most significant developments of the technology in the
      last decade consist in the (i) reduction of the hydrolysis time by the use of
      microwave radiation energy; (ii) improvement in the sensitivity of the residue
      detection, the quantification of the sensitive residues and separation of the
      enantiomeric forms of the amino acids; (iii) application of amino acid analysis
      in the large-scale protein identification by database search; and (iv) gradual
      replacement of the original ion exchange residue separation by reversed-phase
      high-performance liquid chromatography. Amino acid analysis is currently facing
      an enormous competition in the determination of the identity of proteins and
      amino acid homologs by the essentially faster mass spectrometry techniques. The
      amino acid analysis technology needs further simplification and automation of the
      hydrolysis, chromatography and detection steps to withstand the pressure exerted
      by the other technologies.

PMID- 9917166
TI  - Glossary ... managed care.

PMID- 9917167
TI  - People and their family doctors--partners in care, 15th WONCA Conference, Dublin,
      Ireland, June 1998.

PMID- 9917168
TI  - Degenerative disorders of the central nervous system. Proceedings of the annual
      conference of the Polish Association of Neuropathologists. Warszawa, May 24,
      1997.

PMID- 9917169
TI  - North American Society for Pediatric and Adolescent Gynecology 12th annual
      meeting. Palm Beach, Florida, USA. May 28-31, 1998. Abstracts.

PMID- 9917170
TI  - [Proceedings of a symposium on occupational medicine and occupational health.
      Desio, Italy, 7 November 1997].

PMID- 9917171
TI  - [The 100th anniversary of the Department of Normal Physiology of the academician
      I.P. Pavlov St. Petersburg State Medical University].

PMID- 9917172
TI  - A 17-year old Italian boy with a linear lupus erythematosus profundus.

PMID- 9917173
TI  - Guess What! Localised bacillary angiomatosis of the tongue.

PMID- 9917174
TI  - Guess What! Cutaneous Merkel cell carcinoma of the left lower leg.

PMID- 9917175
TI  - Guess What! Myiasis caused by Wohlfahrtia vigil.

PMID- 9917176
TI  - Guess What! Follicular mucinosis.

PMID- 9917177
TI  - Guess What! Lymphangiosarcoma of Stewart-Treves.

PMID- 9917179
TI  - Health hazards and the elderly traveler.

PMID- 9917178
TI  - Analytical techniques mechanisms.

PMID- 9917180
TI  - Travel medicine and Sherlock Holmes.

PMID- 9917181
TI  - Evidence of Dengue virus infection in a German couple returning from Hawaii.

PMID- 9917182
TI  - Ulcerative colitis and colon carcinoma: epidemiology, surveillance, diagnosis,
      and treatment. The Society for Surgery of the Alimentary Tract, American
      Gastroenterological Association American Society for Liver Diseases, American
      Society for Gastrointestinal Endoscopy, American Hepato-Pancreato-Biliary
      Association.

PMID- 9917184
TI  - Risk of cancer in ulcerative colitis.

PMID- 9917183
TI  - Biology of colorectal cancer in ulcerative colitis.

PMID- 9917185
TI  - How reliable/valid is dysplasia in identifying at-risk patients with ulcerative
      colitis?

PMID- 9917187
TI  - Management of dysplasia in ulcerative colitis: is prophylactic colectomy the
      preferred strategy?

PMID- 9917186
TI  - How do we assess the value of surveillance techniques in ulcerative colitis?

PMID- 9917188
TI  - Organ and tissue transplantation in Latvia.
AB  - From 1973 to May, 1996 585 kidney transplantations were performed in the
      Department of Transplantation. From 1983 to 1988 investigations on
      transplantation of pancreas islet cell culture were carried out. Because of
      financial difficulties these investigations had to be stopped. In 1992 a law was
      adopted which regulates organ removal for transplantation by the "option out"
      system. In 1996, a transplantation association of the Baltic countries,
      Balttransplant, which includes the Latvian Department, began to function. Work of
      this association in the field of transplantation coordination has lead to an
      increase of donor kidneys and improvement of graft quality. The center performs
      14-16 transplantations of kidneys per 1 million of population every year. The
      patient one year survival rate is 87%, survival of transplants--72-75%. Further
      progress of transplantation in Latvia will be possible only if the economic
      conditions and progress in medicine in general improve.

PMID- 9917189
TI  - Primary Care Diabetes Conference, 1997: delivering sensitive diabetes care.

PMID- 9917190
TI  - Is there a future for clinical fluorine-18 radiopharmaceuticals (excluding FDG)?
AB  - Merely, asking this question, which as posed by the Editor-in-Chief, implies that
      it cannon easily be answered with a simple yes or no. in fact, it is closely
      related to the question, Is there a future for clinical PET? When looking at the
      world-wide PET radiopharmaceutical production on the basis of a recent IAEA
      directory [1], it is disappointing to see that besides FDG, and to a certain
      extent FDOPA, fluorine-18 radiopharmaceuticals are not widely used. Other 18F
      products, such as fluoride, spiperone derivatives, FMISO, fluoroaltanserin,
      fluorofatty acids and fluoroamino acids, are used by only a few centres. The
      emphasis of this editorial is on clinical radiopharmaceuticals, and in this
      respect the impact of 18F thus far is extremely small, if on excludes FDG. The
      reasons are discussed in this editorial.

PMID- 9917191
TI  - [7th Seminar on hepato-gastroenterology. Paris, France, 21-22 November 1997.
      Proceedings].

PMID- 9917192
TI  - [Effect of botulinum toxin in the treatment of chronic anal fissure].

PMID- 9917193
TI  - Cost effectiveness of treatment for gastro-oesophageal reflux disease in clinical
      practice.

PMID- 9917194
TI  - Cost effectiveness of treatment for gastro-oesophageal reflux.

PMID- 9917195
TI  - Cost effectiveness of treatment for gastro-oesophageal reflux disease.

PMID- 9917196
TI  - Diagnostic value of T cell reactivity in drug induced hepatitis.

PMID- 9917197
TI  - Guidance for trials in Helicobacter pylori infection.

PMID- 9917198
TI  - Clinical trials in Helicobacter pylori infection.

PMID- 9917199
TI  - Dermatitis herpetiformis and cigarette smoking.

PMID- 9917200
TI  - Tomorrow's challenge in liver transplantation: diminishing the imbalance between
      donor organ availability and need.

PMID- 9917201
TI  - Hypotensive action of bromocriptine in the DOCA-salt hypertensive rat:
      contribution of spinal dopamine receptors.
AB  - To assess the role of spinal dopamine receptors in mediation of hypotension
      induced by systemic administration of the dopamine D2 receptor agonist,
      bromocriptine, conscious deoxycorticosterone acetate (DOCA)-salt hypertensive
      rats were pretreated with either intravenous (i.v.; 500 micrograms/kg) or
      intrathecal (i.t.; 40 micrograms/rat at T9-T10) domperidone, a selective dopamine
      D2 receptor antagonist that does not cross the blood-brain barrier. In DOCA-salt
      hypertensive rats, i.v. administration of a sub-maximal dose of bromocriptine
      (150 micrograms/kg) induced a significant decrease in mean aortic pressure (MAP)
      which was greater and longer lasting than that in uninephrectomized control rats.
      Intravenous or i.t. pretreatment with domperidone reduced partially, but
      significantly, the hypotensive effect of bromocriptine (reduction of about 57%
      and 45% of the maximal effect, respectively). The remaining responses observed
      during the 60 min postinjection period were still statistically significant as
      compared with vehicle injection. In contrast, the bromocriptine-induced
      hypotension was fully abolished by i.v. pretreatment with metoclopramide (300
      micrograms/kg), a dopamine D2 receptor antagonist that crosses the blood-brain
      barrier, or by combined pretreatment with i.v. and i.t. domperidone. These
      results suggest that, in DOCA-salt hypertensive rats, the hypotension induced by
      i.v. bromocriptine is mediated partly through a peripheral D2 dopaminergic
      mechanism and partly through stimulation of spinal dopamine D2 receptors, has
      been demonstrated in conscious normotensive rats.

PMID- 9917202
TI  - Global Challenges to Occupational and Environmental Health in the Chemical
      Industry. Proceedings of the XXV Silver Jubilee Medichem Congress. Varna,
      Bulgaria, 30 September-3 October 1997.

PMID- 9917203
TI  - Artificial nutrition in the critically ill.

PMID- 9917204
TI  - Use of CT scan and transesophageal echocardiography in blunt thoracic trauma.

PMID- 9917205
TI  - Raymond L Nimmo and the evolution of trigger point therapy, 1929-1986.

PMID- 9917206
TI  - President's page. HR4250, the Republican House Task Force Managed Care
      legislation.

PMID- 9917207
TI  - Sufi healing practices.

PMID- 9917208
TI  - Subarachnoid hemorrhage: new approaches to the management of cerebral aneurysms.
      Milan, Italy, November 30-December 1, 1995. Proceedings.

PMID- 9917209
TI  - Regarding "Percutaneous ultrasound guided thrombin injection: a new method for
      treating postcatheterization femoral pseudoaneurysms".

PMID- 9917210
TI  - Regarding "The clinical course of asymptomatic mesenteric arterial stenosis".

PMID- 9917211
TI  - The emerging epidemic of atherosclerosis. Call for papers.

PMID- 9917212
TI  - An unprecedented major rearrangement in an arthropod mitochondrial genome.

PMID- 9917213
TI  - Neutrality tests based on the distribution of haplotypes under an infinite-site
      model.

PMID- 9917214
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-1999. A 53-year-old man with fever and rapid neurologic
      deterioration.

PMID- 9917215
TI  - Retraction: suicide after natural disasters.

PMID- 9917216
TI  - Cullen's sign associated with metastatic thyroid cancer.

PMID- 9917217
TI  - Noninvasive positive-pressure ventilation.

PMID- 9917218
TI  - Improvement of hepatic myelopathy after liver transplantation.

PMID- 9917219
TI  - Acute vestibular syndrome.

PMID- 9917220
TI  - Detection of residual disease in childhood acute lymphoblastic leukemia.

PMID- 9917221
TI  - Detection of residual disease in childhood acute lymphoblastic leukemia.

PMID- 9917222
TI  - Myocardial infarction during nifedipine therapy for preterm labor.

PMID- 9917223
TI  - Treatment of hypokalemia.

PMID- 9917224
TI  - Treatment of hypokalemia.

PMID- 9917225
TI  - The stethoscope as a diagnostic aid in tenosynovitis.

PMID- 9917227
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 2-1999. A 15-year-old girl with abdominal pain and bloody stools.

PMID- 9917226
TI  - Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor
      antagonist. L-754,030 Antiemetic Trials Group.
AB  - BACKGROUND: The localization of substance P in brain-stem regions associated with
      vomiting, and the results of studies in ferrets, led us to postulate that a
      neurokinin-1-receptor antagonist would be an antiemetic in patients receiving
      anticancer chemotherapy. METHODS: In a multicenter, double-blind, placebo
      controlled trial involving 159 patients who had not previously received
      cisplatin, we evaluated the prevention of acute emesis (occurring within 24
      hours) and delayed emesis (on days 2 to 5) after a single dose of cisplatin
      therapy (70 mg or more per square meter of body-surface area). Before receiving
      cisplatin, all the patients received granisetron (10 microg per kilogram of body
      weight intravenously) and dexamethasone (20 mg orally). The patients were
      randomly assigned to one of three treatments in addition to granisetron and
      dexamethasone: 400 mg of an oral trisubstituted morpholine acetal (also known as
      L-754,030) before cisplatin and 300 mg on days 2 to 5 (group 1), 400 mg of L
      754,030 before cisplatin and placebo on days 2 to 5 (group 2), or placebo before
      cisplatin and placebo on days 2 to 5 (group 3). Additional medication was
      available at any time to treat occurrences of vomiting or nausea. RESULTS: In the
      acute-emesis phase, 93 percent of the patients in groups 1 and 2 combined and 67
      percent of those in group 3 had no vomiting (P<0.001). In the delayed-emesis
      phase, 82 percent of the patients in group 1, 78 percent of those in group 2, and
      33 percent of those in group 3 had no vomiting (P<0.001 for the comparison
      between group 1 or 2 and group 3). The median nausea score in the delayed-emesis
      phase was significantly lower in group 1 than in group 3 (P=0.003). No serious
      adverse events were attributed to L-754,030. CONCLUSIONS: The neurokinin-1
      receptor antagonist L-754,030 prevents delayed emesis after treatment with
      cisplatin. Moreover, combining L-754,030 with granisetron plus dexamethasone
      improves the prevention of acute emesis.

PMID- 9917228
TI  - Support for new policies to regulate firearms.

PMID- 9917229
TI  - Support for new policies to regulate firearms.

PMID- 9917230
TI  - Support for new policies to regulate firearms.

PMID- 9917231
TI  - Support for new policies to regulate firearms.

PMID- 9917232
TI  - Declining CD4 T-cell counts in a person infected with nef-deleted HIV-1.

PMID- 9917233
TI  - Chlamydia infections in female military recruits.

PMID- 9917234
TI  - Chlamydia infections in female military recruits.

PMID- 9917235
TI  - Mutations of the cystic fibrosis gene and pancreatitis.

PMID- 9917236
TI  - Treatment of fistulas with granulocyte colony-stimulating factor in a patient
      with Crohn's disease.

PMID- 9917237
TI  - Where does the buck stop?

PMID- 9917239
TI  - Transmissible spongiform encephalopathies: neuropathology and phenotypic
      variation. Proceeding of a meeting. Vienna, Austria, May 15-17, 1998.

PMID- 9917238
TI  - Esophageal laceration caused by a bagel.

PMID- 9917240
TI  - European Study Group of Developmental Neuropathology. Oxford, United Kingdom, 3-4
      April 1998.

PMID- 9917241
TI  - 24th Annual meeting of the German-Speaking Society for Neuropediatrics. Hamburg,
      Germany, October 15-17, 1998. Abstracts.

PMID- 9917242
TI  - [Position of the Scientific Medical Council on the antitumor studies conducted in
      Hungary on the Newcastle disease virus].

PMID- 9917243
TI  - [Arnold Winternitz--episodes from the life of a professor of surgery].

PMID- 9917244
TI  - [A nobleman from Szabolcs County in the field of medicine: Lajos Polyak (1864
      1925)].

PMID- 9917245
TI  - [Multiple therapeutic advances].

PMID- 9917246
TI  - The conscious brain: normal and abnormal. Proceedings of a meeting. New York
      City, New York, USA. 5-6 December 1997.

PMID- 9917247
TI  - [Learning with computers].

PMID- 9917248
TI  - [Dentifrices--an educational program on the Internet. HCBE. HyperCorridor-based
      education].

PMID- 9917249
TI  - [The federal ordinance on medical devices (ODim)].

PMID- 9917250
TI  - ["Heartfelt thanks to all who helped us!" The open-door day at the Basel Center
      for Dentistry on 28 August 1998].

PMID- 9917251
TI  - [You have the career maze behind you. Speech on the state examination ceremony in
      dentistry at the University of Zurich of 23 October 1998].

PMID- 9917252
TI  - RNA molecules may carry long-distance signals in plants.

PMID- 9917253
TI  - Iceland OKs private health databank.

PMID- 9917254
TI  - Filling in the blanks of the GABAB receptor.

PMID- 9917255
TI  - Human cloning. Korean report sparks anger and inquiry.

PMID- 9917256
TI  - DNA chips give new view of classic test.

PMID- 9917257
TI  - EPA ponders pesticide tests in humans.

PMID- 9917258
TI  - Borrowing from biology to power the petite.

PMID- 9917259
TI  - Miracle heifer?

PMID- 9917260
TI  - From mice to maize.

PMID- 9917261
TI  - Hominid brain volume.

PMID- 9917262
TI  - Effects of medical research on health care and economy.

PMID- 9917263
TI  - Out of the minds of babes.

PMID- 9917264
TI  - Omnicompetent graduates.

PMID- 9917265
TI  - [Issue dedicated to the 90th birthday of Artashes Ivanovich Karamian (1908
      1989)].

PMID- 9917267
TI  - "Death with dignity".

PMID- 9917268
TI  - Magnet program designates exceptional nursing services.

PMID- 9917269
TI  - Missing in action: nurses in the media.

PMID- 9917270
TI  - The small inhaler.

PMID- 9917271
TI  - The Berman airway.

PMID- 9917273
TI  - Changes for volume 62 

PMID- 9917272
TI  - Proceedings of a workshop on molecular andrology. Giessen, Germany, May 5-6,
      1997.

PMID- 9917274
TI  - Chemical defense in the zebra swallowtail butterfly, Eurytides marcellus,
      involving annonaceous acetogenins.
AB  - Few herbivores feed on the foliage of the North American paw paw tree, Asimina
      triloba; notable exceptions are the larvae of the zebra swallowtail butterfly,
      Eurytides marcellus. Toxic annonaceous acetogenins, produced by A. triloba, are
      responsible for the relative unpalatability of the leaves. Acetogenins found in
      A. triloba extracts are potent pesticidal and antineoplastic agents and have
      emetic activity in vertebrates. In this study, partitioned aqueous MeOH fractions
      of the bioactive CH2Cl2 extracts, of freeze-dried and pulverized larvae, and of
      mature butterflies revealed acetogenin content through the use of HPLC coupled to
      tandem MS (LC-MS/MS). This sensitive technique provides an uncomplicated method
      for the detection of trace compounds and, in this instance, has confirmed tissue
      presence of acetogenins that serve a probable role as chemical defense agents
      against bird predation in zebra swallowtail larvae and adults.

PMID- 9917275
TI  - Occurrence and significance of decahydroquinolines from dendrobatid poison frogs
      and a myrmicine ant: use of 1H and 13C NMR in their conformational analysis 
AB  - Structures for 2,5-disubstituted decahydroquinolines (DHQs) are reported for the
      two diastereomeric pairs cis-275B (14) and cis-275B' (15) and 5-epi-trans-269AB
      (18) and trans-269AB (19), all isolated from skin extracts of dendrobatid frogs,
      and for 5-epi-cis-275B' (16) and 5-epi-trans-275B (17) found in the extracts of
      virgin queens of a myrmicine ant [Solenopsis (Diplorhoptrum) azteca]. Detection
      of such DHQs in an ant, their first reported occurrence, strengthens a dietary
      hypothesis for the origin of the approximately 30 DHQs that have been detected in
      extracts of frog skin. NMR data on the two conformers of cis-decahydroquinoline
      permit assignment of ring conformations and stereochemistry to cis-DHQs of the "N
      endo" type or the "N-exo" type. These conformations are also assigned on whether
      H-8a is equatorial or axial as determined with E-COSY or 1D-HOHAHA spectra.

PMID- 9917276
TI  - Guaianolides as immunomodulators. Synthesis and biological activities of
      dehydrocostus lactone, mokko lactone, eremanthin, and their derivatives.
AB  - The naturally occurring guaianolides, namely mokko lactone (1), dehydrocostus
      lactone (2), eremanthin (3), and related guaianolides, 16, 17, 21, 22, 28-31, 33,
      36, 37, and 39, have been synthesized starting from l-alpha-santonin in an effort
      to examine their structure-activity relationship as inhibitors of the killing
      function of cytotoxic T lymphocytes (CTL) and the induction of intercellular
      adhesion molecule-1 (ICAM-1). It was observed during the present study that the
      guaianolides possessing an alpha-methylene gamma-lactone moiety, i.e., 2, 3, 30,
      33, 37, and 39, exhibited significant inhibitory activity toward the killing
      function of CTL and the induction of ICAM-1.

PMID- 9917278
TI  - Isolation, identification, and enantioselective synthesis of octane-1,3,7-triol:
      determination of its absolute configuration 
AB  - Extracts obtained by solid-phase extraction from apples were separated by
      multilayer countercurrent chromatography. In the most polar fractions, the novel
      octane-1,3,7-triol was identified by 1H and 13C NMR as well as LC-MS and by
      comparison with the synthesized racemic reference compound. Resolution of the
      enantiomers was achieved after acetylation of the triol followed by GC
      separation. The enantioselective synthesis of the stereoisomers of octane-1,3, 7
      triol was performed using the building blocks (R)- and (R, S)-butane-1,3-diol and
      (S)- and (R,S)-butane-1,2,4-triol. Comparison with the isolated products
      indicated that the natural compound consisted of a mixture of (3R,7S)- and
      (3R,7R)-octane-1,3,7-triol in a ratio of 2:3. Since the C3 chiral center is
      enantiomerically pure, the triol might be biogenetically related to the known
      antimicrobial (R)-(+)-octane-1,3-diol, the major volatile compound of some apple
      cultivars.

PMID- 9917277
TI  - Goniotriocin and (2,4-cis- and -trans)-xylomaticinones, bioactive annonaceous
      acetogenins from Goniothalamus giganteus.
AB  - Goniotricin (1) and a mixture of (2,4-cis and -trans)-xylomaticinones (2), new
      bioactive annonaceous acetogenins, were isolated from the bark of Goniothalamus
      giganteus (Annonaceae) by activity-directed fractionation using the brine shrimp
      lethality test. Compound 1 is the first nonadjacent ring-hydroxylated bis
      tetrahydrofuran (THF) acetogenin to be reported. Compound 2 is the cis- and trans
      ketolactone mixture of xylomaticin, a known compound whose absolute
      stereochemistry has not been previously determined. The absolute stereochemistry
      of 2 was determined by the advanced Mosher's ester method. Both 1 and 2 showed
      significant and selective cytotoxicities among the six tumor cell lines in our
      seven-day MTT human solid tumor panel. In the yellow fever mosquito larvae
      microtiter assay, 1 was quite active, with an ED50 value of 3. 5 microg/mL.

PMID- 9917279
TI  - Biotransformation of caryophyllene oxide by botrytis cinerea 
AB  - Biotransformation of caryophyllene oxide (1) with B. cinerea afforded 15 products
      (2-16). Ten of these (3-5, 7, 9-11, and 14-16) are reported here for the first
      time. The main reaction paths involved stereoselective epoxidation at C-8/C-13
      and hydroxylation at C-7. A rearranged compound was found, which was a
      cyclization product 16 possessing the caryolane skeleton.

PMID- 9917280
TI  - Novel labdane diterpenes from the insecticidal plant hyptis spicigera1 
AB  - Seven new labdane diterpenes with insecticidal properties were isolated from the
      aerial parts of Hyptis spicigera. Their structures were established on the basis
      of spectral (MS, 1H NMR, and 13C NMR) and chemical evidences as: 19-acetoxy
      2alpha,7alpha, 15-trihydroxylabda-8(17),(13Z)-diene (1); 15,19-diacetoxy-2alpha,
      7alpha-dihydroxylabda-8(17),(13Z)-diene (2); 7alpha,15, 19-triacetoxy-2alpha
      hydroxylabda-8(17),(13Z)-diene (3); 19-acetoxy-2alpha,7alpha-dihydroxylabda
      8(17),(13Z)-dien-15-al (4); 19-acetoxy-7alpha,15-dihydroxylabda-8(17),(13Z)-dien
      2-one (5); 19-acetoxy-2alpha,7alpha-dihydroxylabda-14, 15-dinorlabd-8(17)-en-13
      one (6); and 2alpha,7alpha,15, 19-tetrahydroxy-ent-labda-8(17),(13Z)-diene (7).
      Absolute configurations were established by application of Mosher's method.
      Compound 2 significantly inhibited larval growth of the European corn borer.

PMID- 9917281
TI  - Tsugicoline E, a new polyoxygenated protoilludane sesquiterpene from the fungus
      laurilia tsugicola1 
AB  - Tsugicoline E (3) has been isolated from cultures of the Basidiomycetous fungus
      Laurilia tsugicola and its structure deduced from 1H and 13C NMR and single
      crystal X-ray diffraction studies. The suggested absolute configuration is
      consistent with biogenetic considerations.

PMID- 9917282
TI  - New products from the reactions of artemisinin with ammonia and amines 
AB  - Reaction of artemisinin (1) with ammonia, methylamine, dimethylamine, and
      allylamine afforded five unexpected products 2-6, in addition to the previously
      reported compounds 7-12. The identities of the new compounds were established
      from their spectral data, by chemical derivatization and by comparison with
      published reports. The stereochemistries of compounds 5 and 6 were confirmed by
      single-crystal X-ray analysis.

PMID- 9917283
TI  - Antiplasmodial and cytotoxic activity of natural bisbenzylisoquinoline alkaloids.
AB  - As part of an ongoing collaborative effort to discover new antimalarial agents
      from natural sources, we have tested 53 bisbenzylisoquinoline alkaloids for
      cytotoxicity against cultured mammalian cells and for antiplasmodial activity
      against chloroquine-sensitive and chloroquine-resistant clones of Plasmodium
      falciparum. The isolates from Cyclea barbata, Stephania pierrei, Stephania
      erecta, Pachygone dasycarpa, Cyclea atjehensis, Hernandia peltata, Curare
      candicans, Albertisia papuana, and Berberis valdiviana exhibited a wide range of
      biological potencies in antiplasmodial assays, and the majority exhibited some
      degree of cytotoxicity against human KB cells. More than half of the compounds
      tested, however, showed selective antiplasmodial activity, with >100-fold greater
      toxicity toward one or both of the P. falciparum clones, relative to cultured
      mammalian cells. The most selective alkaloids were (-)-cycleanine (40), (+)
      cycleatjehine (50), (+)-cycleatjehenine (49), (+)-malekulatine (3), (-)-repandine
      (13), and (+)-temuconine (2). As a result of these studies, relationships between
      the structures, the stereochemistry, and the substitution patterns of these
      alkaloids and their in vitro antiplasmodial and cytotoxic activities are
      beginning to emerge.

PMID- 9917284
TI  - Vismiaphenones D-G, new prenylated benzophenones from Vismia cayennensis.
AB  - Following anti-HIV bioassay-guided fractionation, four new prenylated
      benzophenones, vismiaphenones D-G (7-10), were isolated from extracts of leaves
      of Vismia cayennensis. The structures were elucidated by spectral analyses. Only
      vismiaphenone D (7) exhibited HIV-inhibitory activity in the NCI primary screen.

PMID- 9917285
TI  - Acylated flavonol glycosides from leaves of Stenochlaena palustris.
AB  - From the leaves of Stenochlaena palustris five new O-acylated flavonol
      glycosides, stenopalustrosides A-E (1-5), have been isolated along with five
      known compounds, kaempferol 3-O-(3' '-O-E-p-coumaroyl)-(6' '-O-E-feruloyl)-beta-D
      glucopyranoside (6), kaempferol 3-O-(3' ',6' '-di-O-E-p-coumaroyl)-beta-D
      glucopyranoside (7), kaempferol 3-O-(3' '-O-E-p-coumaroyl)-beta-D-glucopyranoside
      (8), kaempferol 3-O-(6' '-O-E-p-coumaroyl)-beta-D-glucopyranoside (9); and
      kaempferol 3-O-beta-D-glucopyranoside (10). The structures of the isolates were
      elucidated by spectroscopic methods, mainly 1D and 2D NMR. Compounds 1-4 showed
      significant antibacterial activities against Gram-positive strains. The
      structural difference between the isolated antibacterial and nonantibacterial
      compounds is discussed.

PMID- 9917286
TI  - An expeditious procedure for the isolation of ingenol from the seeds of euphorbia
      lathyris 
AB  - A short and practical process for the isolation of ingenol (1a) from an
      agricultural commodity (the seeds of Euphorbia lathyris) is described.
      Macrocyclic diterpene esters are obtained as byproducts, and the esterification
      pattern of the Euphorbia factors L2 (3), L3 (4a), and L8 (4b) was established by
      2D NMR measurements. Full spectroscopic data for these compounds are reported.

PMID- 9917287
TI  - Loloatins A-D, cyclic decapeptide antibiotics produced in culture by a tropical
      marine bacterium.
AB  - Loloatins A (1) to D (4), a family of new cyclic decapeptide antibiotics, have
      been isolated from laboratory cultures of a tropical marine bacterium recovered
      from the Great Barrier Reef in Papua New Guinea. The structures of loloatins A-D
      were elucidated via a combination of spectroscopic analyses and chemical
      degradation. Loloatins A-D exhibit in vitro antimicrobial activity against
      methicillin-resistant Staphyloccoccus aureus, vancomycin-resistant enterococci,
      and drug-resistant Streptococcus pneumoniae.

PMID- 9917289
TI  - Iridal-type triterpenoids with ichthyotoxic activity from belamcanda chinensis 
AB  - Ichthyotoxic activity-guided fractionation of the hexane and ether extracts of
      Belamcanda chinensis (Iridaceae) has resulted in the isolation of eleven iridal
      type triterpenoids including six new compounds, 3-O-tetradecanoyl-16-O
      acetylisoiridogermanal (4), 3-O-decanoyl-16-O-acetylisoiridogermanal (5),
      belachinal (7), anhydrobelachinal (9), epianhydrobelachinal (10), and
      isoanhydrobelachinal (11). Structures of the new iridals were determined by
      spectral and chemical methods. The absolute configuration of isoiridogermanal (1)
      at C-16 was determined to be R by the modified Mosher's method. Of these
      compounds, 16-O-acetylisoiridogermanal (3), 7, and spiroiridal (12) exhibited
      potent ichthyotoxic activity against killie-fish (Oryzias latipes).

PMID- 9917288
TI  - Novel antioxidant compounds from tart cherries (Prunus cerasus).
AB  - As indicated by an Fe(II)-induced liposome peroxidation bioassay, the EtOAc
      extract of tart cherries (Prunus cerasus) was found to have strong antioxidant
      activity. Purification of this extract afforded chlorogenic acid methyl ester (1)
      and three novel compounds, 2-hydroxy-3-(o-hydroxyphenyl) propanoic acid (2); 1
      (3', 4'-dihydroxycinnamoyl)-cyclopenta-2,5-diol (3), and 1-(3', 4'
      dihydroxycinnamoyl)-cyclopenta-2,3-diol (4), as determined by their spectral
      data. At a 20-microM concentration, the antioxidant activities of compounds 3 and
      4 were comparable to the antioxidant activities of caffeic acid, whereas compound
      1 showed activity similar to chlorogenic acid. Also, these compounds showed
      antioxidant activities similar to the commercial antioxidants tert
      butylhydroquinone and butylated hydroxytoluene. However, compound 2 was not
      active when tested at a 100-microM concentration.

PMID- 9917291
TI  - Alvaradoins A-D. Anthracenone C arabinosides from alvaradoa jamaicensis 
AB  - The aerial parts of Alvaradoa jamaicensis have yielded four new compounds. These
      are both C-10 epimers of 10-C-[4'-O-acetyl-3'-O-(3-methylbut-2-enoyl)]-beta-D
      arabinopyranosyl -1,8-dihydroxy-6-methoxy-3-methyl-anthracen-9(10H)-one (3 and 4)
      and of 10-C-[4'-O-acetyl-3'-O-(3-methylbut-2-enoyl)]-beta-D-arabinopyranosyl 
      1,8,10-trihydroxy-6-methoxy-3-methyl-anthracen-9-one (5 and 6). The
      anthraquinones chrysophanol (1) and physcion (2) were also isolated.

PMID- 9917290
TI  - Novel anti-HIV lancilactone C and related triterpenes from Kadsura lancilimba.
AB  - Three new triterpene lactones, lancilactones A (1), B (2), and C (3), together
      with the known kadsulactone A (4), were isolated from the stems and roots of
      Kadsura lancilimba. Their structures and stereochemistries were determined
      primarily from mass and NMR spectral data. Compound 3 inhibited HIV replication
      with an EC50 value of 1.4 microg/mL and a therapeutic index of greater than 71.4.

PMID- 9917292
TI  - Structure-antimutagenic activity relationship study of plicatin B.
AB  - A systematic structure-activity relationship study of plicatin B (1), an
      antimutagenic constituent of Psoralea juncea, was undertaken with a view toward
      elucidating its chemical mode of action and possibly optimizing its antimutagenic
      activity during the process. Compound 1 and its related analogues were examined
      for their antimutagenic activity against mutations induced by ethyl
      methanesulfonate, a direct acting mutagen and alkylating agent, in Salmonella
      typhimurium strain TA100, utilizing the modified Ames test protocol. The dihydro
      analogue 3 resulting from saturation of the conjugated alkene double bond of 1
      was found to exhibit reduced cytotoxicity and enhanced efficacy relative to the
      parent compound. This result serves preliminarily to exclude a Michael acceptor
      role of the alpha,beta-unsaturated carbonyl moiety in connection with its
      antimutagenic activity.

PMID- 9917293
TI  - Isolation and structure revision of pepluane diterpenoids from euphorbia peplus 
AB  - A new pepluane diterpene polyester (2) was isolated from a CH2Cl2 extract of the
      whole, undried plant of Euphorbia peplus, together with the known compound 1. The
      structures were established by high-field spectroscopic methods, including 2D NMR
      techniques, and by X-ray crystallography, and the stereostructure of the first
      member of the pepluane diterpenoids (1) was revised.

PMID- 9917294
TI  - Isoterracinolides A and B, novel bishomoditerpene lactones from euphorbia
      terracina 
AB  - An extract of Euphorbia terracina L. has yielded six acylated polyhydroxy
      terpenoid lactones (1-6), which all display the C22 17-ethyljatrophane carbon
      framework. Four of these (1-4) are delta lactones belonging to the previously
      described terracinolide type, and two of them (2, 3) are new. Two further new
      compounds have been named isoterracinolides A (5) and B (6) and exhibit an eight
      membered lactone ring. Another isolated new compound is the jolkinolide-type, ent
      abietane gamma lactone (7).

PMID- 9917295
TI  - Three new metabolites from marine-derived fungi of the genera coniothyrium and
      microsphaeropsis 
AB  - The marine sponges Ectyplasia perox and Myxilla incrustans were investigated for
      associated fungal strains. Among others, a Coniothyrium sp., from E. perox, and a
      Microsphaeropsis sp., from M. incrustans, were isolated, cultured, and
      investigated for their biologically active secondary metabolite contents. The new
      compound microsphaeropsisin (1) together with the known compounds (R)-mellein
      (4), (3R,4S)-hydroxymellein (5), (3R,4R)-hydroxymellein (6), and 4, 8-dihydroxy
      3,4-dihydro-2H-naphthalen-1-one (7) were isolated from the Microsphaeropsis sp.
      From culture extracts of the Coniothyrium sp., the new compounds (3S)-(3',5'
      dihydroxyphenyl)butan-2-one (2) and 2-(1'(E)-propenyl)-octa-4(E),6(Z)-diene-1,2
      diol (3), together with the six known metabolites (3R)-6-methoxymellein (8), (3R)
      6-methoxy-7-chloromellein (9), cryptosporiopsinol (10), phenylethanol, (p
      hydroxyphenyl)ethanol, and 2-(hydroxymethyl)furan, were obtained. All structures
      were determined using spectroscopic methods. With the exception of 3, all
      compounds were tested for their antimicrobial properties, and all but 10
      demonstrated significant antimicrobial activity in agar diffusion assays.

PMID- 9917296
TI  - The structure of mithramycin reinvestigated.
AB  - A reinvestigation of the structure of mithramycin, the principal product of
      Streptomyces argillaceus ATCC 12956, is reported. The structure elucidation was
      carried out with mithramycin decaacetate (4) using 2D NMR methods, including
      TOCSY, HMBC, and HSQC experiments. The work resulted in structure 3being
      confirmed for mithramycin.

PMID- 9917297
TI  - New acetylenic enol ethers of glycerol from the sponge Petrosia sp.
AB  - Ten acetylenic enol ethers of glycerols, including six new compounds (1-6) and a
      linear acetylenic alcohol (7), have been isolated from a sponge of the genus
      Petrosia. The structures of the novel compounds were elucidated by spectroscopic
      methods. The absolute stereochemistry of 1-7 was determined by chemical
      transformations and the Mosher method. Some of these compounds exhibited weak
      cytotoxicity against a human leukemia cell-line (K-562).

PMID- 9917298
TI  - Phenylpropanoid glycosides from Penstemon serrulatus.
AB  - Two new phenylpropanoid glycosides named cis-martynoside (1) and cis
      leucosceptoside A (3) were recognized in cell suspension cultures of Penstemon
      serrulatus Menz. The structures of these compounds were determined on the basis
      of 1H NMR spectral data.

PMID- 9917299
TI  - Guttiferone F, the first prenylated benzophenone from Allanblackia stuhlmannii.
AB  - The HIV-inhibitory activity in extracts of Allanblackia stuhlmannii was tracked,
      via bioassay-guided fractionation, to a new member of the camboginol/guttiferone
      class of prenylated benzophenones, guttiferone F (1). The structure was solved by
      extensive NMR analyses and by acid-catalyzed conversion to 30-epi-cambogin (4).
      This is the first report of this compound type in the genus Allanblackia.

PMID- 9917300
TI  - A new biologically active acylated triterpene saponin from Silene fortunei.
AB  - A new acylated triterpene-saponin (1), together with a mixture of the known
      jenisseensosides C and D, has been isolated from the roots of Silene fortunei.
      The structure of the new compound was established by chemical means and
      spectroscopic methods as 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl]-28 -O- [[alpha-L-arabinopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl- (1-->3)-b eta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl
      (1-->2)]-[beta-D- glucopyranosyl-(1-->3)]-4-O-acetyl-beta-D
      fucopyranosyl]quillaic acid. This saponin showed a significant enhancement of
      granulocyte phagocytosis in vitro.

PMID- 9917301
TI  - Koninginin G, a new metabolite from trichoderma aureoviride 
AB  - A new metabolite, koninginin G (1), was isolated from a strain of Trichoderma
      aureoviride and its structure established by the interpretation of spectroscopic
      data. The metabolite significantly inhibited the growth of etiolated wheat
      coleoptiles by 56% at 10(-3) M.

PMID- 9917302
TI  - A new taxoid, 19-acetoxytaxagifine, from Taxus chinensis.
AB  - A new taxane diterpene, 19-acetoxytaxagifine (1), was isolated from an ethanol
      extract of the aerial parts of Taxus chinensis. Its structure was determined on
      the basis of spectral evidence.

PMID- 9917304
TI  - Thalprzewalskiinone, a new oxobenzylisoquinoline alkaloid from thalictrum
      przewalskii 
AB  - A novel oxobenzylisoquinoline alkaloid, thalprzewalskiinone (1), was isolated
      from the roots of Thalictrum przewalskii, and its structure was established via
      spectroscopic analysis. Five other alkaloids were isolated: the protoberberines
      pseudocoptisine and berberine, the aporphines (+)-N-methylnantenine and (+)
      magnoflorine, and the simple isoquinolone N-methyl-6,7-dimethoxyisoquinolone.
      Isovanillin was also isolated from this extract.

PMID- 9917305
TI  - New taxoids from the seeds of taxus chinensis 
AB  - Two new taxoids, 2alpha-acetoxy-2',7-dideacetoxyaustrospicatine (1) and
      decinnamoyltaxinine E (2), have been isolated from the extracts of the seeds of
      the Chinese yew Taxus chinensis (Pilg.) Rehd. in addition to taxuspine Z (3),
      taxin B (4), taxezopidine G (5), 7, 2'-bisdeacetoxyaustropicatine (6), 5alpha
      cinnamoyl-9alpha,10beta, 13alpha-triacetoxytaxa-4(20),11-diene (7), taxachitriene
      A, 20-deacetyltaxachitriene A, 13-O-acetylbrevifoliol, taxinines A and J, and
      taxacin. The structures of these compounds were elucidated on the basis of
      spectral analysis and chemical derivatizations.

PMID- 9917303
TI  - 13C labeling indicates that the epoxide-containing amino acid of HC-toxin is
      biosynthesized by head-to-tail condensation of acetate.
AB  - HC-toxin, cyclo(D-Pro-L-Ala-D-Ala-L-Aeo), where Aeo stands for 2-amino-9,10-epoxi
      8-oxodecanoic acid, is a potent inhibitor of histone deacetylase. Previous
      molecular genetic studies indicated that HC-toxin biosynthesis requires a
      dedicated fatty acid synthase. The incorporation of [13C]acetate into HC-toxin
      was studied using NMR. The pattern of incorporation of 13C was consistent with
      the carbons of Aeo being derived from head-to-tail condensation of acetate.

PMID- 9917306
TI  - A new epidioxy sterol as an antifouling substance from a palauan marine sponge,
      lendenfeldia chondrodes 
AB  - Bioassay-guided fractionation of an extract of a marine sponge, Lendenfeldia
      chondrodes, has led to the isolation and identification of new epidioxy sterols
      1a and 1b as an inseparable mixture. Two known epidioxy sterols 2 and 3 and three
      known sesterterpenes 4-6 were also isolated from the same extract. These
      compounds showed repellent activity against the blue mussel Mytilus edulis
      galloprovincialis.

PMID- 9917308
TI  - Longithorones J and K, two new cyclofarnesylated quinone derived metabolites from
      the australian ascidian aplidium longithorax 
AB  - Chemical investigation of a Great Barrier Reef ascidian, Aplidium longithorax,
      has resulted in the isolation of two new cyclofarnesylated quinone-derived
      compounds, longithorones J (1) and K (2). Longithorone J (1) is the first example
      of a gamma-hydroxy-cyclohexenone in this structure class. Longithorone K (2) is a
      dihydro analogue of longithorone B.

PMID- 9917307
TI  - Geniculol, a new biologically active diterpene from the endophytic fungus
      geniculosporium sp.1 
AB  - An endophytic fungus of the genus Geniculosporium was isolated from Teucrium
      scorodonia. The EtOAc extract of this isolate exhibited antialgal activities, as
      well as demonstrating an interesting profile during chemical screening. After
      mass cultivation of this fungus, in an optimized agar medium, two of the
      compounds responsible for the observed biological activity were isolated, the new
      diterpene geniculol (1), and the known fungal metabolite cytochalasin F (2).
      Geniculol is an unprecedented and irregular diterpenoid. For 1 and 2 complete 1H
      and 13C NMR data are reported. Both metabolites exhibit algacidal properties.
      Additionally, cytochalasin F was shown to be an inhibitor of photosynthesis,
      suggesting an ecological function in the plant-symbiont relationship for this
      secondary metabolite.

PMID- 9917309
TI  - Laevisines A and B: two new sesquiterpene-pyridine alkaloids from maytenus laevis
AB  - Two new sesquiterpene-pyridine alkaloids, laevisines A (1) and B (2), have been
      isolated from the bark of Maytenus laevis, along with seven known alkaloids (3
      9). Their structures were elucidated by FABMS analysis and 1D and 2D NMR
      spectroscopy including DQF-COSY, HSQC, and HMBC.

PMID- 9917310
TI  - Cytotoxic isoprenylated flavans of Broussonetia kazinoki.
AB  - Two new prenylflavans [kazinols Q (1) and R (2)] and five known compounds
      [kazinols D (3), K (4), and H, 7,4'-dihydroxyflavan (5), and oleanolic acid] were
      isolated from the root bark of Broussonetia kazinoki. The cytotoxic activity of 1
      5 was evaluated against several different cell lines.

PMID- 9917311
TI  - Aplidioxins A and B, two new dibenzo-p-dioxins from the ascidian aplidiopsis
      ocellata 
AB  - Two new substituted dibenzo-p-dioxins, aplidioxins A (1) and B (2), were isolated
      from the ascidian Aplidiopsis ocellata. The structures of these compounds were
      elucidated by a combination of 1D and 2D NMR spectroscopy and an X-ray analysis
      of aplidioxin A.

PMID- 9917312
TI  - Aurantoside C, a new tetramic acid glycoside from the sponge Homophymia conferta.
AB  - A new tetramic acid glycoside, aurantoside C (3), was isolated from the sponge
      Homophymia conferta and the structure was determined by detailed 1D and 2D NMR
      analysis of the natural product and a hexaacetate derivative.

PMID- 9917314
TI  - A novel lathyrane diterpenoid from the roots of euphorbia lathyris 
AB  - A new lathyrane diterpene (1) has been isolated and characterized from a CH2Cl2
      extract of the roots of Euphorbia lathyris. Detailed spectral analysis revealed
      that the structure of 1, including relative stereochemistry, is that of a diester
      of a hitherto unknown, polyfunctional diterpene parent alcohol.

PMID- 9917313
TI  - Discorhabdin P, a new enzyme inhibitor from a deep-water Caribbean sponge of the
      genus Batzella.
AB  - Discorhabdin P (1), a new discorhabdin analogue, has been isolated from a deep
      water marine sponge of the genus Batzella. Discorhabdin P (1) inhibited the
      phosphatase activity of calcineurin and the peptidase activity of CPP32. It also
      showed in vitro cytotoxicity against P-388 and A-549 cell lines. The isolation
      and structure elucidation of discorhabdin P (1) are described.

PMID- 9917316
TI  - Solakhasoside, a novel steroidal saponin from Solanum khasianum.
AB  - Solakhasoside (1), a novel steroidal saponin, was isolated from the fruit of
      Solanum khasianum. Its structure was determined as (23S, 25S)-spirot-5-en
      3beta,17alpha, 23-triol-3-O-[alpha-L-rhamnopyranosyl-(1-->2)[beta-D-xylopyranosyl
      (1 -->3)]-beta-D-galactopyranoside] (1) by spectroscopic analysis.

PMID- 9917315
TI  - A new sinapoyl derivative of isovitexin 6'' -O-beta-D-glucopyranoside from
      Alliaria petiolata.
AB  - The new compound 6'''-O-sinapoylisovitexin 6'' -O-beta-D-glucopyranoside (1) was
      isolated from the foliage of Alliaria petiolata, and identified by spectral
      studies.

PMID- 9917317
TI  - New alkaloids from the indopacific sponge Stylissa carteri.
AB  - Two samples of the marine sponge Stylissa carteri collected in Indonesia yielded
      two new bromopyrrole alkaloids: debromostevensine (1) and debromohymenin (2), as
      well as nine other known congeners (3-11). The structures of the new compounds
      were unambiguously established on the basis of their NMR and mass spectra.

PMID- 9917318
TI  - New 12a-hydroxyrotenoids from gliricidia sepium bark 
AB  - The investigation of a methanolic extract of Gliricidia sepium bark afforded, in
      addition to vestitol and 2'-O-methylvestitol, three new 12a-hydroxyrotenoids,
      gliricidol (1), 2-methoxygliricidol (2), and gliricidin (3). The structures of 1
      3 were elucidated by analysis of their spectroscopic data. Compounds 1-3
      exhibited activity against Artemia salina larvae.

PMID- 9917319
TI  - Alkylfurans: effects of alkyl side-chain length on insecticidal activity.
AB  - The insecticidal activity of five alkylfurans against the generalist insect
      herbivore beet armyworm, Spodoptera exigua, was examined. Two naturally occurring
      compounds, the avocadofurans 2-(pentadecyl)furan (1) and 2-(heptadecyl)furan (2),
      previously isolated from specialized avocado idioblast oil cells, and three
      homologues, 2-(tetradecyl)furan (3), 2-(hexadecyl)furan (4), and 2
      (octadecyl)furan (5), were synthesized. Bioassays of alkylfurans 1-5 using a 9
      day diet-incorporation initiated with neonates showed that all alkylfurans tested
      significantly increased S. exigua larval mortality and reduced larval weights,
      with maximal biological activity detected among the naturally occurring
      alkylfurans 1 and 2.

PMID- 9917320
TI  - Steroidal glycosides from the bulbs of Allium jesdianum.
AB  - Phytochemical analysis of the fresh bulbs of Allium jesdianum yielded four
      steroidal glycosides, (22S)-cholest-5-ene-1beta,3beta, 16beta,22-tetrol 1,16-di-O
      beta-D-glucopyranoside (1), (22S)-cholest-5-ene-1beta,3beta,16beta,22-tetrol 1-O
      alpha-L-rhamnopyranosyl 16-O-beta-D-glucopyranoside (2), (25R)-5alpha-spirostane
      2alpha,3beta-diol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1
      ->3)] -O-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside] (F-gitonin) (3),
      and (25R)-5alpha-spirostane-2alpha,3beta, 6alpha-triol 3-O-[O-beta-D
      glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1-->3)] -O-beta-D-glucopyranosyl
      (1-->4)-beta-D-galactopyranoside] (4). Compound 2 is a new natural product, and 4
      is a new spirostanol saponin. Compound 3 was found to exhibit cytostatic and
      cytotoxic activities against several malignant tumor cells.

PMID- 9917321
TI  - Two novel lanostane-type triterpenes from the stem bark of abies mariesii 
AB  - Two novel lanostane-type triterpene lactones, 3alpha, 11alpha-dihydroxy-7
      oxolanosta-8,24-dien-26,23(R)-olide (1) and 1alpha,3alpha,11alpha-trihydroxy-7
      oxolanosta-8,24-dien-26, 23(R)-olide (2), were isolated from the stem bark of
      Abies mariesii, together with a known triterpene, 3-oxo-9betaH-lanosta-7,24-dien
      26, 23(R)-olide. The structures of 1 and 2 were determined on the basis of 2D NMR
      techniques.

PMID- 9917322
TI  - An enzyme-based formaldehyde assay and its utility in a sponge sterol
      biosynthetic pathway 
AB  - An enzyme-based assay has been developed and utilized to confirm the production
      of formaldehyde in the dealkylation of sterol side chains in a marine sponge. The
      enzyme used in the assay, formaldehyde dehydrogenase, is NAD+ dependent, and the
      assay measures the production of NADH by determining the increase in fluorescence
      at 460 nm.

PMID- 9917323
TI  - Chemical modification and site-directed mutagenesis of methionine residues in
      recombinant human granulocyte colony-stimulating factor: effect on stability and
      biological activity.
AB  - Chemical modification and mutagenesis of methionines in recombinant human
      granulocyte colony-stimulating factor (G-CSF) were investigated. Selective
      oxidation of G-CSF by H2O2 and t-butyl hydroperoxide leads to generation of
      different oxidized forms. Four modified forms were isolated and shown to contain
      1 to 4 oxidized methionyl residues. All methionines in G-CSF are reactive, with
      reaction kinetics following the order of Met1>Met138>Met127>>>Met122. H2O2
      oxidation of Met122 is relatively slow and is biphasic with a faster second
      reaction phase being affected by the oxidation of Met127. All oxidized forms
      retain gross G-CSF conformation similar to that of the native molecule and are
      able to bind the soluble G-CSF receptor. However, G-CSF form oxidized at both
      Met127 and Met122 is unstable and exhibits decreased ability to dimerize the
      receptor after exposure to acid or elevated temperature. All modified forms,
      except Met1-oxidized G-CSF, also show significantly lower biological activity.
      Our data suggest that Met138 is solvent accessible and its surrounding
      microenvironment may be critical for G-CSF function, whereas Met127 is less
      accessible to solvent and Met122 is near the hydrophobic core. Oxidation at both
      Met127 and Met122 results in alterations of G-CSF structure that affect the
      apparent molecular size, polarity, and stability and lead to the loss of G-CSF
      biological function. G-CSF variants with Leu replacement at Met127 or at Met138
      are not completely resistant to oxidation-induced inactivation, while the variant
      with Leu replacement at both sites is more stable and can retain in vitro
      biological activity following oxidation.

PMID- 9917324
TI  - Geranoyl-CoA carboxylase: a novel biotin-containing enzyme in plants.
AB  - Geranoyl-CoA carboxylase (EC 6.4.1.4) is a biotin-containing enzyme previously
      described in two genera of bacteria. Here we report the presence of geranoyl-CoA
      carboxylase in kingdom Plantae. Geranoyl-CoA carboxylase was purified 180-fold
      from maize leaves. The enzyme has a biotin-containing subunit of 122 kDa. The pH
      optimum for activity is 8.3. The apparent Km values for the substrates geranoyl
      CoA, bicarbonate, and ATP are 64 +/- 5 microM, 0. 58 +/- 0.04 mM, and 8.4 +/- 0.4
      microM, respectively. Subcellular fractionations indicate that geranoyl-CoA
      carboxylase is located in plastids. Geranoyl-CoA carboxylase activity is
      ubiquitous in organs of monocots and dicots and varies with development. We
      postulate that geranoyl-CoA carboxylase plays an important role in isoprenoid
      catabolism in plants, in a pathway analogous to that shown in Psuedomonas sp. In
      plants, this catabolic pathway would require the interaction of at least three
      subcellular compartments (plastids, microbodies, and mitochondria) and two biotin
      containing enzymes, geranoyl-CoA carboxylase and 3-methylcrotonyl-CoA
      carboxylase.

PMID- 9917325
TI  - Characterization of a human digestive tract-specific calpain, nCL-4, expressed in
      the baculovirus system.
AB  - Human nCL-4, a digestive tract-specific calpain, was stably produced with 30K, a
      regulatory subunit for ubiquitous calpain as a fully active form using the
      baculovirus-expression system. nCL-4 showed an activity only when it was
      coexpressed with 30K. Expressed heterodimeric recombinant nCL-4 was purified to
      near homogeneity by sequential column chromatographies. Purified nCL-4 showed a
      calcium-dependent activity (calcium concentration at 50% maximum activity (Ka):
      0.125 mM) with a sp act of 21 U/mg, which is distinct from those of ubiquitous
      calpains. nCL-4 exhibited calcium-dependent autolysis, but the cleavage pattern
      of nCL-4 was clearly different from ubiquitous calpains. Although it was
      inhibited by leupeptin, E-64, and calpastatin, and exhibited an optimal pH at 7.3
      like other ubiquitous calpains, its optimal temperature was much lower. When
      overexpressed in COS-7 cells, clear asymmetric juxtanuclear, and/or nuclear
      staining rather than typical cytoplasmic staining was observed. Moreover, a
      translation product of nCL-4 was detected in rat stomach tissue by
      immunofluorescence analysis. In conclusion, human nCL-4 resembles ubiquitous
      calpain in some enzymatic properties and interacts with 30K for its activity.
      This is the first report on biochemical and enzymatic properties of a fully
      active tissue-specific calpain species expressed in the baculovirus system.

PMID- 9917326
TI  - Hepatocyte nuclear factor 4-mediated activation of rat CYP3A1 gene and its modes
      of modulation by apolipoprotein AI regulatory protein I and v-ErbA-related
      protein 3.
AB  - CYP3A1 gene (P450/6betaB) encodes testosterone 6beta-hydroxylase (EC 1.14.14.1)
      in rats. The promoter region of CYP3A1 gene contains three binding sites for
      nuclear factors: 6betaB-A (-105 to -86), 6betaB-B (-139 to -118), and 6betaB-C (
      164 to -145). The 6betaB-A site shows a high degree of similarity to a consensus
      sequence of the binding site of hepatocyte nuclear factor 4 (HNF-4) and also to
      the 6betaA-A site on the rat CYP3A2 gene promoter region. Our previous study
      suggested an involvement of the 6betaA-A site in the basal transactivation of
      CYP3A2 gene using HepG2 cells. In the present study, transactivation through the
      6betaB-A and 6betaA-A sites of CYP3A1 and CYP3A2 genes has directly been shown by
      coexpression of HNF-4 and CYP3A1 or CYP3A2 promoter-reporter fused genes. Similar
      experiments further showed that nuclear factor binding at the 6betaB-B site
      hampered HNF-4-mediated transactivation of CYP3A1 gene. Recombinant
      apolipoprotein AI regulatory protein I (ARP-1) and v-ErbA-related protein 3 (EAR
      3) are shown to suppress HNF-4-mediated activation at the 6betaB-B site without
      competition of HNF-4.

PMID- 9917327
TI  - Elevated O-linked N-acetylglucosamine metabolism in pancreatic beta-cells.
AB  - High intracellular glucose concentrations increase flux though the hexosamine
      biosynthetic pathway, resulting in elevated UDP-N-acetylglucosamine (GlcNAc)
      concentrations. The nucleocytoplasmic enzyme O-linked N
      acetylglucosaminyltransferase (OGT) uses UDP-GlcNAc as a donor to modify numerous
      critical substrates, including nuclear pore proteins and transcription factors.
      Here, we document (a) the overwhelming enrichment of pancreatic OGT transcripts
      in the beta-cells of the islets of Langerhans, (b) the physiologically
      significant increase in the level of O-GlcNAc residues present in beta-cells, and
      (c) the action of streptozotocin, a close analogue of GlcNAc, to selectively
      inhibit O-GlcNAcase, an enzyme involved in the removal of O-GlcNAc residues.
      Taken together, these findings suggest that pancreatic beta cells maintain a
      highly elevated O-GlcNAc metabolism and that the diabetes inducing drug
      streptozotocin inhibits O-GlcNAcase.

PMID- 9917328
TI  - Ectonucleotidases of avian gizzard smooth muscle and liver plasma membranes: a
      comparative study.
AB  - Extracellular nucleotides, e.g., ATP, ADP, and UTP, are important signaling
      molecules which elicit various physiological responses in different tissues.
      Their degradation is catalyzed by ectonucleotidases which are located on cell
      surfaces. Most tissues have a mixed population of ectonucleotidases. In this
      report, the ATP and ADP hydrolyzing ectonucleotidases of chicken gizzard smooth
      muscle and liver plasma membranes were studied. The two membranes exhibited
      marked differences in the ratio of ATPase/ADPase activities, activation by
      divalent cations, thermal stability, responses to detergents and cross-linking
      agents, and sensitivity to several enzyme inhibitors. The ATPase activity of
      chicken gizzard membranes is (i) labile to heat and detergents; (ii) activated by
      concanavalin A and disuccinimidyl suberate, both cross-linking agents; (iii)
      inhibited by mercurials; and (iv) insensitive to high concentrations of azide, a
      known inhibitor of ecto-ATP diphosphohydrolases (ecto-ATP/Dase). In contrast, the
      liver membrane ATPase and ADPase activities are more stable to treatment by heat
      and detergents and insensitive to cross-linking agents and mercurials, but are
      inhibited by azide. A low ADP hydrolase activity in the gizzard membranes could
      be distinguished from both the gizzard ATPase and the liver ATPase/ADPase. This
      ADP hydrolase, which is markedly stimulated by NBD-Cl, accounts for most of the
      ADP hydrolysis activity in gizzard membranes. It is concluded that the major
      ectonucleotidase in the gizzard membranes is an ecto-ATPase whereas that in the
      liver membranes is an ecto-ATP/Dase. That both membranes contain a mixed
      population of the ecto-ATPase and ecto-ATP/Dase, but in different proportions, is
      further demonstrated by immunochemical characterization. The different
      composition of ectonucleotidases in the two membranes is expected to have an
      important effect on the regulation of hydrolysis of extracellular ATP as well as
      the concentration of extracellular adenine nucleotides in the gizzard and liver
      tissues.

PMID- 9917330
TI  - S-nitrosylation and S-glutathiolation of protein sulfhydryls by S-nitroso
      glutathione.
AB  - The modification of reactive protein sulfhydryls by S-nitrosoglutathione and
      other NO donors has been studied by gel isoelectric focusing. S-nitrosylated,
      unmodified, and S-glutathiolated protein forms are differentiated by this method.
      With specific antibodies for the protein of interest, both S-nitrosylation and S
      glutathiolation of the protein were analyzed in mixtures obtained as soluble
      tissue or cell extracts. The effect of S-nitrosoglutathione (GSNO) on purified
      phosphorylase b, on carbonic anhydrase III in an extract from rat liver, and on H
      ras expressed in Escherichia coli was examined. When fresh GSNO reacted with pure
      phosphorylase b, only S-nitrosylated forms of the protein were observed. Likewise
      the NO donors, amyl nitrite, spermine NONOate, and diethylamine NONOate, all
      generated S-nitrosylated phosphorylase b. When crude mixtures of proteins from
      rat liver (containing carbonic anhydrase III) or from E. coli (containing an
      overexpressed form of H-ras) were exposed to fresh GSNO, both the S-nitrosylated
      and the S-glutathiolated forms of the proteins were observed. It is suggested
      that reactive intermediates from the breakdown of GSNO are responsible for the
      observed S-glutathiolation. These experiments show that both S-nitrosylated and S
      glutathiolated forms of proteins may be generated by the addition of GSNO to
      mixtures containing proteins with reactive sulfhydryls. These protein
      modifications may exhibit metabolic consequences independent of the release of
      nitric oxide.

PMID- 9917329
TI  - Manganese superoxide dismutase protects mitochondrial complex I against
      adriamycin-induced cardiomyopathy in transgenic mice.
AB  - Adriamycin (ADR) is a potent anticancer drug that causes severe cardiomyopathy.
      We have previously demonstrated that ADR-induced ultrastructural mitochondrial
      injury in the heart was attenuated in manganese superoxide dismutase (MnSOD)
      transgenic mice. To further investigate the biochemical mechanisms by which MnSOD
      protected mitochondria against ADR-induced damage, cardiac mitochondrial function
      and activities were evaluated. The results showed that ADR caused significant
      decrease in state 3 respiration and respiratory control ratio using both complex
      I and II substrates in nontransgenic mice. In transgenic mice, state 3
      respiration for complex I substrates remained unaffected by ADR, but was reduced
      for complex II substrate. Complex I activity was significantly decreased in
      nontransgenic, but not in transgenic mice after ADR treatment, suggesting that
      mitochondrial complex I is sensitive to inactivation by superoxide radicals. The
      activities of complex II and mitochondrial creatine kinase were decreased by ADR
      in both nontransgenic and transgenic mice. These results support our previous
      observations on the protective role of MnSOD on the ultrastructural damage of the
      heart after ADR treatment and extend the understanding of its mechanisms in
      mitochondria.

PMID- 9917331
TI  - Mechanistic studies of catechins as antioxidants against radical oxidation.
AB  - The antioxidative mechanisms of catechins were studied by investigating products
      generated at the first stages by 2, 2'-azobis(2-aminopropane)hydrochloride (AAPH)
      induced radical oxidation, without any isolation, using LC/MS, spectrophotometry,
      and PM3 semiempirical molecular orbital (MO) calculations. Catechins were quite
      effective in scavenging peroxyl radicals in a liposomal system and in an aqueous
      system except for (-)-epigallocatechin (EGC). EGC was the least effective among
      four catechins tested. From the results of LC/MS and spectroscopic studies, (-)
      epicatechin (EC) would be gently converted to an anthocyanin-like compound.
      According to the mechanisms, the compound produced from EC by radical oxidation
      can also function as an antioxidant. As a result, EC has a longer inhibition
      period (tinh = 9360 s). On the other hand, EGC decreased shortly after oxidation
      (tinh = 3420 s) and was transformed to a quinone-like compound. The addition of
      superoxide dismutase (SOD) reduced the chemiluminescence from EGC during
      oxidation. Active oxygen including superoxide anion radicals (O-2) may be
      produced in the case of EGC, but not in the case of EC. However, EGC has a more
      rapid scavenging effect on peroxyl radicals (kinh/kp = 232) than EC (kinh/kp =
      41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the
      C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic
      sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be
      abstracted by free radicals. The authors propose the tentative antioxidative
      mechanisms of catechins depending on the experimental results and theoretical
      calculations.

PMID- 9917332
TI  - The optical biosensor studies on the role of hydrophobic tails of NADPH
      cytochrome P450 reductase and cytochromes P450 2B4 and b5 upon productive complex
      formation within a monomeric reconstituted system.
AB  - The optical biosensor study of interaction between microsomal proteins-NADPH
      cytochrome P450 reductase, cytochrome P450 2B4, and cytochrome b5-was carried out
      in the monomeric reconstituted system in the absence of phospholipids. The
      formation of individual complexes was kinetically characterized and their
      association and dissociation rate constants were determined. The association rate
      constants for the complexes formed were found to be close to the diffusiion limit
      (0.5-4) x 10(6) M-1 s-1-while their dissociation rate constants did not exceed
      0.5 s-1. It was shown that the interprotein electron transfer can occur both
      through complex formation and due to random collision. The dominant role of
      hydrophobic membraneous protein fragments in formation of productive electron
      transfer complexes was demonstrated.

PMID- 9917333
TI  - Myoglobin-induced oxidative damage: evidence for radical transfer from oxidized
      myoglobin to other proteins and antioxidants.
AB  - Reaction of equine Fe(III) myoglobin with H2O2 gives rise to an Fe(IV)-oxo
      species at the heme center and protein (globin)-derived radicals. Studies have
      shown that there are two (or more) sites for the protein-derived radical: at
      tyrosine (Tyr-103) or tryptophan (Trp-14). The latter radical reacts rapidly with
      oxygen to give a Trp-derived peroxyl radical. The formation of both the tyrosine
      phenoxyl radical and the tryptophan-derived peroxyl species have been confirmed
      in the present study; the latter appears to be the major initial radical, with
      the phenoxyl radical appearing at longer reaction times, possibly via secondary
      reactions. We have investigated, by EPR spectroscopy, the reactivity of the Trp
      14 peroxyl radical with amino acids, peptides, proteins, and antioxidants, with
      the aim of determining whether this species can damage other targets, i.e.,
      whether intermolecular protein-to-protein radical transfer and hence chain
      oxidation occurs, and the factors that control these reactions. Three amino acids
      show significant reactivity: Tyr, Trp, and Cys, with Cys the least efficient.
      Evidence has also been obtained for (inefficient) hydrogen abstraction at peptide
      alpha-carbon sites; this may result in backbone cleavage in the presence of
      oxygen. The myoglobin Trp-14 peroxyl radical has been shown to react rapidly with
      a wide range of proteins to give long-lived secondary radicals on the target
      protein. These reactions appear to mainly involve Tyr residues on the target
      protein, although evidence for reaction at Trp has also been obtained.
      Antioxidants (GSH, ascorbate, Trolox C, vitamin E, and urate) react with the
      myoglobin-derived peroxyl radical; in some cases antioxidant-derived radicals are
      detected. These reactions are only efficient at high antioxidant concentrations,
      suggesting that protein-to-protein damage transfer and protein chain-oxidation
      may occur readily in biological systems.

PMID- 9917334
TI  - Formation of long-lived radicals on proteins by radical transfer from heme
      enzymes--a common process?
AB  - Incubation of Fe(III)myoglobin (Fe(III)Mb) with H2O2 in the presence of bovine
      serum albumin (BSA) has been shown previously to give albumin-derived radicals as
      a result of radical transfer from myoglobin to BSA. In this study the occurrence
      of similar processes with peroxidases has been investigated using horseradish
      peroxidase (HRP)/H2O2, in the presence and absence of added tyrosine. Incubation
      of HRP with H2O2 and bovine or human serum albumins, in the presence and absence
      of tyrosine, gave long-lived albumin-derived radicals as detected by EPR
      spectroscopy. Evidence has been obtained for these albumin radicals being located
      on buried tyrosine residues on the basis of blocking experiments. The effect of
      protein conformation on radical transfer has been investigated using partial
      proteolytic digestion prior to protein oxidation. With HRP/H2O2/BSA and
      Fe(III)Mb/H2O2/BSA increased radical concentrations were observed after limited
      digestion, although this effect was less marked with the HRP/H2O2/BSA system than
      with Fe(III)Mb/H2O2/BSA, consistent with different modes of radical transfer.
      More extensive digestion of BSA decreased the radical concentration to levels
      below those detected with native albumin, indicating that the tertiary structure
      of the target protein plays an important role in determining the rate of radical
      transfer and/or the stability of the resultant species. These results are
      consistent with a mechanism for the HRP/H2O2/no free tyrosine system involving
      radical transfer to the albumin via the heme edge of the peroxidase. In contrast,
      albumin radical formation by the HRP/H2O2/free tyrosine system was only
      marginally affected by proteolysis, consistent with free tyrosine phenoxyl
      radicals being the mediators of radical transfer, without significant protein
      protein interaction. These protein-to-protein radical transfer reactions may have
      important consequences for understanding protein oxidation in biological systems.

PMID- 9917335
TI  - Mechanism of stimulation of glucose transport by H2O2: role of phospholipase C.
AB  - Exposure of Clone 9 cells, a rat liver cell line, to hydrogen peroxide (H2O2)
      resulted in a striking and rapid stimulation of glucose transport (8- to 10-fold
      in 1 h). A comparable response was found in 3T3-L1 preadipocytes, C2C12
      myoblasts, and NIH 3T3 fibroblasts, which, similar to Clone 9 cells, express only
      the Glut 1 glucose transporter isoform. The enhancement of glucose transport in
      Clone 9 cells in response to H2O2 was significantly attenuated by genistein and
      the phospholipase C (PLC) inhibitor, U73122. Exposure to H2O2 resulted in a rise
      in cell sn-1,2-diacylglycerol content, and the rise was significantly inhibited
      by U73122. Moreover, the H2O2-induced stimulation of glucose transport was
      significantly blocked by thapsigargin. Neither staurosporine nor a 24-h
      preincubation in the presence of phorbol-12-myristate-13-acetate (TPA) affected
      the stimulatory effect of hydrogen peroxide on glucose transport. The activity of
      big mitogen-activated kinase (BMK1) and of stress-activated protein kinase
      (SAPK), both members of mitogen-activated protein kinases, were enhanced in
      response to exposure to H2O2; however, neither protein kinase appeared to be
      linked to the enhancement of glucose transport by H2O2. It is concluded that the
      stimulation of glucose transport in response to H2O2 is independent of changes in
      PKC, BMK1, and SAPK activity, and is mediated, at least in part, through H2O2
      induced stimulation of protein tyrosine kinase and PLC pathways.

PMID- 9917336
TI  - Rhodobacter capsulatus DNA topoisomerase I purification and characterization.
AB  - A 30-kDa DNA topoisomerase has been purified to near homogeneity from the purple
      nonsulfur photosynthetic bacterium Rhodobacter capsulatus. The enzyme is
      recognized by an antibody against a 16-mer peptide sequence from human DNA
      topoisomerase I. The purified enzyme is a type I topoisomerase. Consistent with
      the properties of other prokaryotic type I DNA topoisomerases, the isolated
      enzyme is unable to relax positively supercoiled DNA and absolutely requires
      divalent cations for its relaxation activity. However, regardless of the Mg+2
      concentrations, ATP concentrations above 5 mM completely inhibit the relaxing
      activity. The enzyme is sensitive to high salt concentrations and the optimal
      activity occurs at salt concentrations between 3 and 30 mM for monovalent
      cations. Single-stranded M13 DNA is a strong inhibitor of this relaxing activity.
      The enzyme is inhibited by ethidium bromide, confirming that this DNA
      topoisomerase is incapable of relaxing positive supercoils. Topoisomerase I
      specific inhibitors like Hoechst 32258 and actinomycin D inhibit the enzymatic
      activity while the enzyme is resistant to type II topoisomerase inhibitors such
      as norfloxacin, nalidixic acid, and novobiocin. From these enzymatic
      characteristics, we conclude that the R. capsulatus DNA topoisomerase is a
      prokaryotic type I DNA topoisomerase.

PMID- 9917337
TI  - Analysis of purified maize starch synthases IIa and IIb: SS isoforms can be
      distinguished based on their kinetic properties.
AB  - Since starch synthases IIa (SSIIa) and SSIIb have not been purified from plant
      tissue, their structure-function relationships have not been well characterized.
      Therefore, we have expressed these SS genes in Escherichia coli, purified them to
      apparent homogeneity, and studied their kinetic properties. In addition, the N
      terminally truncated forms of these enzymes were studied in an attempt to
      understand the function of the diverse N-terminal sequences in SS. Our results
      show that, like SSI, the N-terminal extensions of SSIIa and SSIIb are not
      essential for catalytic activity and no extensive changes in their kinetic
      properties are observed upon their N-terminal truncation. Each isoform of SS can
      be distinguished based on its kinetic properties. Maize SSI and maize SSIIb
      exhibit higher Vmax with glycogen as a primer, while the converse is true for
      SSIIa. However, the specific activity of SSIIb is at least two- to threefold
      higher than that for either SSI or SSIIa. Although SSIIb exhibits the highest
      maximal velocity of the isoforms compared, its apparent affinity for primer is
      twofold lower than the affinity of SSI and SSIIa for primer. Perhaps these
      differences in primer affinity, primer preference, and maximal velocities all
      contribute in some way to the different structure(s) of starch during its
      synthesis. Expression and purification of maize SS has now provided us a useful
      tool to address the role(s) of SS in starch synthesis and starch structure.

PMID- 9917338
TI  - Copper oxidation of in vitro dioleolylphosphatidylcholine-enriched high-density
      lipoproteins: physicochemical features and cholesterol effluxing capacity.
AB  - Susceptibility of lipoproteins to oxidation is partly determined by their content
      in endogenous antioxidants, but also by the polyunsaturated fatty acids
      (PUFA)/monounsaturated fatty acids (MUFA) ratio. The aim of our study was to
      enrich human high-density lipoproteins (HDLs) with dioleoylphosphatidylcholine
      (DOPC) in order to modify the PUFA/MUFA ratio while maintainig the alpha
      tocopherol/PUFA ratio constant and to appreciate the consequences of this
      enrichment before and after copper-induced oxidation. The enrichment of HDLs with
      DOPC was obtained by incubation of these lipoproteins with DOPC liposomes and
      further reisolation of HDLs. The consequent 40% HDL enrichment in MUFA was
      concomitant with a 35% loss in PUFA (MUFA/PUFA ratio = 1.43). The enrichment of
      HDLs with DOPC led to a 40% decrease in alpha-tocopherol content, which kept a
      constant alpha-tocopherol/PUFA ratio. The DOPC-HDLs exhibited a lower
      oxidizability by copper than the nonenriched HDLs (NE-HDLs), as shown by their
      twofold longer lag phase and the threefold lower propagation rate. Moreover, DOPC
      HDLs led to a six- to sevenfold lower production of hydroperoxide molecular
      species from phosphatidylcholine and cholesteryl esters than NE-HDLs after 24 h
      copper oxidation. With regard to the cholesterol effluxing capacity, copper
      oxidation of HDLs led to a decrease of this property. However, our results
      clearly showed that DOPC enrichment of HDLs allowed us to keep a better effluxing
      capacity than in NE-HDLs after 24 h oxidation (22.3% vs 17.4%, respectively).
      Since apo A-I was degraded as well in DOPC-HDLs as in NE-HDLs, the better
      effluxing capacity of DOPC-HDLs could not come from a preserved integrity of apo
      A-I. It could be partly related to the improved fluidity of oxidized DOPC-HDLs
      compared to oxidized NE-HDLs, as shown by electron spin resonance data
      (correlation-relaxation time at 24 degreesC = 2.20 ns vs 3.00 ns after 24 h
      oxidation, in DOPC-HDLs and in NE-HDLs, respectively). Besides, it could also be
      hypothesized that the sevenfold lower content of phosphatidylcholine
      hydroperoxides in DOPC-HDLs than in NE-HDLs after 24 h copper oxidation could be
      involved in the better ability of oxidized DOPC-HDLs to mobilize cellular
      cholesterol.

PMID- 9917339
TI  - Metmyoglobin/azide: the effect of heme-linked ionizations on the rate of complex
      formation.
AB  - The kinetics of formation and dissociation of the horse metmyoglobin/azide
      complex has been investigated between pH 3.5 and 11.5. The ionic strength
      dependence of the reaction has been determined at integral pH values between 5
      and 10. Hydrazoic acid, HN3, binds to metmyoglobin with a rate constant of (3.8
      +/- 1.0) x 10(5) M-1 s-1. Protonation of a group with an apparent pKa of 4.0 +/-
      0.3 increases the rate of HN3 binding 6.5-fold to (2.5 +/- 0.8) x 10(6) M-1 s-1.
      The ionizable group is attributed to the distal histidine, His-64. The azide
      anion, N-3, binds to metmyoglobin with a rate constant of (4.7 +/- 0.3) x 10(3) M
      1 s-1, about two orders of magnitude slower than HN3. Conversion of
      aquometmyoglobin to hydroxymetmyoglobin slows azide binding significantly.
      Binding of HN3 to hydroxymetmyoglobin cannot be detected, while N-3 binds to
      hydroxymetmyoglobin with a rate of 5.7 +/- 3.2 M-1 s-1, almost three orders of
      magnitude slower than N-3 binding to aquometmyoglobin. Protonation of the distal
      histidine facilitates HN3 dissociation from the complex. HN3 dissociates from the
      metmyoglobin/azide complex with a rate constant of 18 +/- 6 s-1, while the azide
      anion dissociates with a rate constant of 0.16 +/- 0.02 s-1, about 100 times
      slower. The apparent pKa for His-64 is essentially the same in metmyoglobin and
      the metmyoglobin/azide complex, 4.0 +/- 0.3 and 4.4 +/- 0.2, respectively. The
      ionic strength dependence of the observed association rate constant is influenced
      by both primary and secondary kinetic salt effects. The primary kinetic salt
      effect is anomalous, with the rate of N-3 binding decreasing with increasing
      ionic strength above the isoelectric point of metmyoglobin where the protein has
      a net negative charge. The ionic strength dependence of the dissociation rate
      constant can be described solely in terms of the ionic strength dependence of the
      acid dissociation constant for His-64 in the metmyoglobin/azide complex, a
      secondary kinetic salt effect.

PMID- 9917340
TI  - Transcriptional regulation of cellular retinol-binding protein, type II gene
      expression in small intestine by dietary fat.
AB  - We have previously demonstrated that dietary fat, especially unsaturated fatty
      acids, induces cellular retinol-binding protein, type II (CRBPII) gene expression
      in rat jejunum. In the present study, we showed that feeding a high-fat diet
      caused parallel increases in jejunal CRBPII mRNA and CRBPII pre-mRNA levels.
      Nuclear run-on assay also revealed that this increase of CRBPII mRNA level by
      high-fat diet was, at least in part, triggered at a transcription level.
      Moreover, peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA level
      was also increased in the jejunum by high-fat diet. Gel shift assay showed that
      the binding activity of rat jejunal nuclear protein to the nuclear receptor
      response elements located in the rat CRBPII gene (RXRE and RE3) was greater in
      rats fed high-fat diet than in those fed fat-free diet and were enhanced by
      addition of bacterially expressed PPARalpha protein. Also PPARalpha-retinoid X
      receptor alpha (RXRalpha) heterodimer was capable of binding to the CRBPII-RXRE
      and RE3 elements and these binding activities were enhanced by addition of some
      PPARalpha ligands in the gel shift assay. Taken together, these studies suggest
      that dietary fatty acids may lead to induction of CRBPII gene transcription
      through increases of PPARalpha as well as its ligand levels.

PMID- 9917341
TI  - Role of active-site residues 107 and 108 of glutathione S-transferase mGSTA4-4 in
      determining the catalytic properties of the enzyme for 4-hydroxynonenal.
AB  - The murine alpha-class glutathione S-transferase mGSTA4-4 displays a high
      catalytic activity with 4-hydroxynonenal (4-HNE), a cytotoxic product of lipid
      peroxidation. The X-ray crystal structure of mGSTA4-4 was used to design
      mutations targeting the 4-HNE binding site, with the goal of defining the
      structural elements of the mGSTA4-4 protein necessary for the high conjugative
      activity with 4-HNE. Two candidate positions, 107 and 108, were investigated. Of
      these, residue 108 appears to be significant in codetermining the catalytic
      properties of mGSTA4-4 toward 4-HNE. Systematic mutagenesis of amino acid 108
      indicated that high activity toward 4-HNE is contingent on the presence of an
      aliphatic, hydrophobic side chain in this position. In particular, replacement of
      the wild-type V108 with leucine led to a more than fivefold increase in both
      absolute activity of the enzyme for 4-HNE and its selectivity for 4-HNE over the
      model substrate 1-chloro-2,4-dinitrobenzene, due to a selective increase of the
      turnover number for 4-HNE with no change in the affinity of the protein for this
      substrate and no changes in the kinetic parameters for 1-chloro-2,4
      dinitrobenzene. In contrast, the A107L mutation decreased activity of the enzyme
      for both 4-HNE and CDNB and partially reversed the positive effect of the V108L
      mutation in a double mutant.

PMID- 9917342
TI  - Isolation and characterization of a Delta 5-fatty acid desaturase from
      Caenorhabditis elegans.
AB  - Arachidonic acid and eicosapentaenoic acid are important precursors for the
      production of prostaglandins and other hormone-like eicosanoid molecules. These
      fatty acids are synthesized by animals by elongating and desaturating precursor
      fatty acids such as linoleic acid (18:2Delta9,12) and alpha-linolenic acid
      (18:3Delta9, 12,15). We have identified a Delta5 fatty acid desaturase gene (fat
      4) from the nematode Caenorhabditis elegans. We have expressed this gene product
      in Saccharomyces cerevisiae and demonstrate that it readily converts di-homo
      gamma-linolenic acid (20:3Delta8,11,14) to arachidonic acid (20:4Delta5,8,11,14).
      The FAT-4 Delta5-desaturase also acts on a number of other substrates, including
      fatty acids that do not contain a double bond at the Delta8 position.

PMID- 9917343
TI  - Bombesin promotes synergistic stimulation of DNA synthesis by ethanol and insulin
      in fibroblasts.
AB  - In NIH 3T3 fibroblasts and several other cellular systems, ethanol (50-80 mM) was
      previously shown to greatly enhance the mitogenic effects of insulin particularly
      in the presence of zinc. Here we report that in NIH 3T3 fibroblasts the combined
      stimulatory effects of ethanol and insulin on DNA synthesis can be further
      increased by bombesin both in the absence and presence of zinc. Bombesin also
      enhanced insulin-plus-ethanol-induced DNA synthesis in mouse Swiss 3T3 and Balb/c
      3T3 fibroblasts, but in these cells bombesin was effective only in the presence
      of zinc. In NIH 3T3 fibroblasts, the potentiating effects of ethanol on insulin
      induced DNA synthesis by the zinc-dependent and bombesin-dependent mechanisms
      were additive. Wortmannin, an inhibitor of phosphatidylinositol 3'-kinase (PI3K),
      prevented the comitogenic effect of ethanol in the presence of bombesin but not
      in the presence of zinc. Furthermore, bombesin, but not ethanol, was found to
      enhance the stimulatory effect of insulin on PI3K activity. Rapamycin, an
      indirect inhibitor of p70 S6 kinase actions, inhibited the comitogenic effects of
      ethanol in the presence of both zinc and bombesin. However, only ethanol, but not
      bombesin, enhanced the stimulatory effect of insulin on p70 S6 kinase activity;
      this effect of ethanol was zinc-dependent. Neither ethanol nor bombesin enhanced
      the stimulatory effects of insulin on the phosphorylation (activation) of
      p38/p42/p44 mitogen-activated protein kinases. The results suggest that in mouse
      fibroblasts maximal stimulation of DNA synthesis by physiologically relevant
      concentrations of ethanol occurs if both PI3K and p70 S6 kinase are activated.
      These data suggest a mechanism by which ethanol may affect growth in affected
      human tissues during its tumor promoting actions.

PMID- 9917344
TI  - Membrane permeability modeling: Kedem-Katchalsky vs a two-parameter formalism.
AB  - The analysis of experiments for the purpose of determining cell membrane
      permeability parameters is often done using the Kedem-Katchalsky (KK) formalism
      (1958). In this formalism, three parameters, the hydraulic conductivity (Lp), the
      solute permeability (Ps), and a reflection coefficient (final sigma), are used to
      characterize the membrane. Sigma was introduced to characterize flux interactions
      when water and solute (cryoprotectant) cross the membrane through a common
      channel. However, the recent discovery and characterization of water channels
      (aquaporins) in biological membranes reveals that aquaporins are highly selective
      for water and do not typically cotransport cryoprotectants. In this circumstance,
      sigma is a superfluous parameter, as pointed out by Kedem and Katchalsky. When
      sigma is unneeded, a two-parameter model (2P) utilizing only Lp and Ps is
      sufficient, simpler to implement, and less prone to spurious results. In this
      paper we demonstrate that the 2P and KK formalism yield essentially the same
      result (Lp and Ps) when cotransporting channels are absent. This demonstration is
      accomplished using simulation techniques to compare the transport response of a
      model cell using a KK or 2P formalism. Sigma is often misunderstood, even when
      its use is appropriate. It is discussed extensively here and several simulations
      are used to illustrate and clarify its meaning. We also discuss the
      phenomenological nature of transport parameters in many experiments, especially
      when both bilayer and channel transport are present.

PMID- 9917345
TI  - Hydraulic conductivity (Lp) and its activation energy (Ea), cryoprotectant agent
      permeability (Ps) and its Ea, and reflection coefficients (sigma) for golden
      hamster individual pancreatic islet cell membranes.
AB  - Long-term cryopreservation of islets of Langerhans would be advantageous to a
      clinical islet transplantation program. Fundamental cryobiology utilizes
      knowledge of basic biophysical characteristics to increase the understanding of
      the preservation process and possibly increase survival rate. In this study
      several of these previously unreported characteristics have been determined for
      individual islet cells isolated from Golden hamster islets. Using an electronic
      particle counting device and a temperature control apparatus, dynamic volumetric
      response of individual islet cells to anisosmotic challenges of 1.5 M dimethyl
      sulfoxide (DMSO) and 1.5 M ethylene glycol (EG) were recorded at four
      temperatures (8, 22, 28, and 37 degreesC). The resulting curves were fitted using
      Kedem and Katchalsky equations which describe water flux and cryoprotectant agent
      (CPA) flux based on hydraulic conductivity (Lp), CPA permeability (Ps), and
      reflection coefficient (final sigma) for the membrane. For Golden hamster islet
      cells, Lp, Ps, and final sigma for DMSO at 22 degreesC were found to be 0.23 +/-
      0.06 microm/min/atm, 0.79 +/- 0.32 x 10(-3) cm/min, and 0.55 +/- 0.37 (n = 11)
      (mean +/- SD), respectively. For EG at 22 degreesC, Lp equaled 0.23 +/- 0.06
      microm/min/atm, Ps equaled 0.63 +/- 0.20 x 10(-3) cm/min, and final sigma was
      0.75 +/- 0.17 (n = 9). Arrhenius plots (ln Lp or ln Ps versus 1/temperature (K))
      were created by adding the data from the other three temperatures and the
      resulting linear regression yielded correlation coefficients (r) of 0.99 for all
      four plots (Lp and Ps for both CPAs). Activation energies (Ea) of Lp and Ps were
      calculated from the slopes of the regressions. The values for DMSO were found to
      be 12.43 and 18.34 kcal/mol for Lp and Ps (four temperatures, total n = 52),
      respectively. For EG, Ea of Lp was 11.69 kcal/mol and Ea of Ps was 20.35 kcal/mol
      (four temperatures, total n = 58).

PMID- 9917346
TI  - Stabilization of rat liver mitochondrial alanine aminotransferase with ethanol
      and trehalose.
AB  - Rat liver mitochondrial alanine aminotransferase (mALT) is known to be a very
      unstable enzyme, a property that has hindered efforts to purify it. In this
      report we examine the possibility of stabilizing mALT with ethanol, trehalose,
      and protease inhibitors. The presence of ethanol was shown to slow down the
      inactivation of mALT, increasing its half-life from 1 to 4 h. Trehalose was found
      to greatly enhance the stability of mALT in a concentration-dependent manner. In
      the presence of 36.5% trehalose, the half-life of mALT was 85 h. Of the protease
      inhibitors tested only antipain and chymostatin slowed down the inactivation of
      mALT but only within the first 24 h following preparation of the crude enzyme. It
      is concluded that the inclusion of ethanol and trehalose in purification
      protocols could aid the purification of the enzyme. It is also concluded that the
      inclusion of protease inhibitors in purification protocols of mALT may not be
      necessary as its inactivation does not seem to be due to protease activity.

PMID- 9917347
TI  - The influence of temperature on metabolic and cellular protection of the heart
      during long-term ischemia: a study using P-31 magnetic resonance spectroscopy and
      biochemical analyses.
AB  - We have compared the influence of two different cold temperatures (below 10
      degreesC) for cardiac ischemia by measuring a large variety of hemodynamic and
      metabolic parameters during ischemia and reflow. Isolated isovolumic rat hearts
      were arrested with a preservation solution which was developed in our laboratory
      and then submitted to 5 h of cold storage (4 degreesC, group I; and 7.5 degreesC,
      group II) in the same solution. After an additional period of 50 min of ischemia
      at 15 degreesC with intermittent cardioplegic infusion, hearts were reperfused
      for 60 min at 37 degreesC. Function was assessed during the control period and
      reflow. High-energy phosphates and intracellular pH were followed by 31P magnetic
      resonance spectroscopy. Analyses of metabolites and enzymes were performed by
      biochemical assays and HPLC in coronary effluents and in freeze-clamped hearts to
      assess cellular integrity. The energetic pool was better preserved at 4 degreesC
      during ischemia (ATP at the end of 4 degreesC ischemia, 59 +/- 7% in group I vs
      31 +/- 5% in group II, P < 0.01) and reflow (P < 0.05) but membrane protection
      was higher when increasing the temperature to 7.5 degreesC (reduction of creatine
      kinase leakage, 89 +/- 16 IU/min in group I vs 51 +/- 5 IU/min in group II, P <
      0.05). As a result, functional recovery, represented by the rate pressure
      product, was higher in hearts preserved at 7.5 degreesC (52 +/- 6% recovery in
      group I vs 77 +/- 7% in group II at the end of reflow, P < 0.05). Altogether,
      cold storage at 7.5 degreesC provides a better protection than storage at 4
      degreesC.

PMID- 9917348
TI  - Effect of different concentrations of cryoprotectant and extender on the hatching
      of indian major carp embryos (Labeo rohita, catla catla, and cirrhinus mrigala)
      stored at low temperature 
AB  - Rohu (Labeo rohita), catla (Catla catla) and mrigal (Cirrhinus mrigala) embryos
      were examined for hatching success after short-term (8-13 h) storage at low
      temperature (4 degreesC) using three concentrations of three cryoprotectants,
      methanol (1, 2, and 3 M), dimethyl sulfoxide (1.282, 1.923, and 2.564 M, equal to
      10, 15, and 20%), and glycerol (1.087, 1.63, and 2.174 M, equal to 10, 15, and
      20%), separately as well as together with a single concentration of sucrose (0.5
      M). The aim was to determine the toxicity of cryoprotectants for fish embryos at
      4 degreesC. Of the cryoprotectants used, methanol was found to be most suitable
      for low-temperature storage in the refrigerator. The hatching rate of embryos was
      significantly higher when sucrose was added to methanol when compared with
      methanol alone. Of the three concentrations of methanol tested, survival was
      maximal at 2 M in the presence of 0.5 M sucrose (rohu, 57.5 +/- 5.24; catla, 47.5
      +/- 5.24; and mrigal, 32. 5 +/- 5.24). Both rohu and catla embryos survived with
      either 1 or 2 M methanol, with or without the addition of sucrose, but the
      addition of sucrose was essential for survival of mrigal at 1 and 2 M methanol.
      Copyright 1998 Academic Press.

PMID- 9917349
TI  - Mouse spermatozoa in high concentrations of glycerol: chemical toxicity vs
      osmotic shock at normal and reduced oxygen concentrations.
AB  - The cryobiological preservation of mouse spermatozoa has presented difficulties
      in the form of poor motilities or irreproducibility. We have identified several
      likely underlying problems. One is that published studies have used
      concentrations of the cryoprotectant glycerol that are substantially lower (0.3
      M) than the approximately 1 M concentrations that are optimal for most cells.
      Another may arise from the known high susceptibility of mouse sperm to free
      radical damage. We have identified two contributors to damage from higher
      concentrations of glycerol, namely, chemical toxicity proportional to
      concentration and exposure time and osmotic damage arising from too rapid an
      addition and removal of the glycerol. When toxicity is minimized by restricting
      the exposure time to 1 or 5 min and osmotic shock is minimized by adding and
      removing the glycerol stepwise, relatively high percentages of the sperm survive
      contact with 0.8 M glycerol. Free-radical damage in mouse sperm is known to be
      proportional to the oxygen concentration. We have determined the consequences of
      reducing the oxygen to <3% of atmospheric by the use of a bacterial membrane
      preparation, Oxyrase. Oxyrase reduced damage from centrifugation and
      substantially reduced damage from osmotic shock; however, it did not
      significantly reduce glycerol toxicity.

PMID- 9917350
TI  - Successful recovery of motility and fertility of cryopreserved cane toad (Bufo
      marinus) sperm 
AB  - The recent decline and extinction of amphibian species is a worldwide phenomenon
      without an identified cause or solution. Assisted reproductive technologies,
      including sperm cryopreservation, are required to manage endangered amphibian
      species and preserve their genetic diversity. This study on the Anuran amphibian
      (Bufo marinus) was undertaken to determine the feasibility of cryopreservation of
      amphibian sperm. Sperm suspensions for cryopreservation were prepared by
      macerating testes in cryoprotective additives of 10% (w/v) sucrose or 10% (w/v)
      sucrose containing either 10, 15, or 20% (v/v) glycerol or 10, 15, or 20% (v/v)
      dimethyl sulfoxide (Me2SO). Suspensions were then cooled to -85 degreesC using a
      controlled rate cooler, stored in LN2, and thawed in air. The motility and
      fertilization rate of cryopreserved suspensions and unfrozen control suspensions
      in Simplified Amphibian Ringer were compared. Sucrose alone had no cryoprotective
      effect. All other treatments showed varying degrees of recovery of motility and
      fertilizing capacity. High rates of recovery of motility and fertilizing capacity
      were observed with 15% Me2SO (68.9 +/- 3.8 and 60.5 +/- 4.7%) and 20% glycerol
      (58.0 +/- 5.9 and 81.4 +/- 4.3%), respectively. Motility and fertilization rates
      were similar with Me2SO but diverged with glycerol as cryoprotectant. The data
      demonstrate the feasibility of using sperm cryopreservation with amphibian
      species. Copyright 1998 Academic Press.

PMID- 9917351
TI  - Cryopreservation of unfertilized mouse oocytes: the effect of replacing sodium
      with choline in the freezing medium.
AB  - Although embryo cryopreservation has become commonplace in many species,
      effective methods are not available for routine freezing of unfertilized eggs.
      Cryopreservation-induced damage may be caused by the high concentration of sodium
      ions in conventional freezing media. This study investigates the effect of a
      newly developed low-sodium choline-based medium (CJ2) on the ability of
      unfertilized, metaphase II mouse eggs to survive cryopreservation and develop to
      the blastocyst stage in vitro. Specifically, the effects of cooling to subzero
      temperatures, thawing rate, LN2 plunge temperature, and equilibration with a low
      sodium medium prior to freezing are examined. In contrast to cooling to 23, 0, or
      -7.0 degreesC in a sodium-based freezing medium (ETFM), cooling in CJ2 had no
      significant negative effect on oocyte survival or development. Oocytes frozen in
      CJ2 survived plunging into LN2 from -10, -20, or -33 degreesC at significantly
      higher rates than oocytes frozen in ETFM. With the protocol used (1.5 M PrOH, 0.1
      M sucrose, -0.3 C/min, plunging at -33 degreesC) rapid thawing by direct
      submersion in 30 degreesC water was more detrimental to oocyte survival than
      holding in air for 30 or 120 s prior to transfer to water. Equilibration of
      unfertilized oocytes with a low-sodium medium prior to cryopreservation in CJ2
      significantly increased survival and blastocyst development. These results
      demonstrate that the high concentration of sodium in conventional freezing media
      is detrimental to oocyte cryopreservation and show that choline is a promising
      replacement. Reducing the sodium content of the freezing medium to a very low
      level or eliminating sodium altogether may allow oocytes and other cells to be
      frozen more effectively.

PMID- 9917352
TI  - Observation of two inorganic phosphate NMR resonances in the perfused hypothermic
      rat heart.
AB  - The effect of hypothermia on isolated perfused rat hearts was studied with 31P
      NMR. Hearts were continuously perfused with phosphate-free Krebs-Henseleit buffer
      while the perfusate temperature was adjusted. Perfusate pH was kept at 7.40 +/-
      0.02 throughout the experiments. Using the chemical shift difference between PCr
      and Pi the intracellular pH was estimated. At 36, 20, and 10 degreesC a cytosolic
      alkalinization at a pH of 7.05 +/- 0.04, 7.21 +/- 0.05, and 7.40 +/- 0.03 was
      observed, respectively. At 10 degreesC two Pi resonances were observed with a
      separation of 0.25 ppm. This resonance corresponded to a Pi resonance of a
      cellular compartment with a local pH of 7.78 +/- 0.06, likely mitochondrial. This
      additional resonance disappeared upon warming of the hearts back to 36 degreesC.

PMID- 9917353
TI  - Generation of dendritic cells from fresh and frozen cord blood CD34+ cells.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that are required
      for the initiation of the immune response. DCs have been shown to be generated
      from CD34(+) pluripotent hematopoietic progenitor cells in the bone marrow and
      cord blood (CB), but relatively little is known about the effect of
      cryopreservation on functional maturation of DCs from hematopoietic stem cells.
      In this work we report the generation of DCs from cryopreserved CB CD34(+) cells.
      CB CD34(+) cells were cryopreserved at -80 degreesC for 2 days. Cryopreserved CB
      CD34(+) cells as well as freshly isolated CB CD34(+) cells cultured with
      granulocyte-macrophage colony-stimulating factor (GM-CSF)/stem cell factor
      (SCF)/tumor necrosis factor-alpha (TNF-alpha) for 14 days gave rise to
      CD1a+/CD4(+)/CD11c+/CD14(-)/CD40(+)/CD80(+ )/CD83(+)/CD86(+)/HLA-DR+ cells with
      dendritic morphology. DCs derived from cryopreserved CB CD34(+) cells showed a
      similar endocytic capacity for fluorescein isothiocyanate-labeled dextran and
      lucifer yellow when compared with DCs derived from freshly isolated CB CD34(+)
      cells. Flow cytometric analysis revealed that two CC chemokine receptors (CCRs),
      CCR-1 and CCR-3, were expressed on the cell surface of DCs derived from both
      cryopreserved and freshly isolated CB CD34(+) cells, and these DCs exhibited
      similar chemotactic migratory capacities in response to regulated on activation
      normal T-cell expressed and secreted. DCs derived from cryopreserved as well as
      freshly isolated CB CD34(+) cells were more efficient than peripheral blood
      mononuclear cells in the primary allogeneic T-cell response. These results
      indicate that frozen CB CD34(+) cells cultured with GM-CSF/TNF-alpha/SCF gave
      rise to dendritic cells which were morphologically, phenotypically and
      functionally similar to DCs derived from fresh CB CD34(+) cells.

PMID- 9917354
TI  - The effect of superoxide dismutase on the recovery of human bone marrow
      hemopoietic stem cells stored at 4 degreesC.
AB  - The effect of superoxide dismutase (SOD) on the recovery of human hemopoietic
      stem cells stored at 4 degreesC has been studied. Human bone marrow cells from
      cancer patients without hemopoietic diseases were stored at 4 degreesC for 1-7
      days in RPMI 1640 medium containing 10% human AB serum with or without 6 U/ml of
      SOD. The recovery of colony-forming units of the following types were counted:
      granulocyte and macrophage type; megakaryocyte type; mixed granulocyte,
      erythrocyte, megakaryocyte, and macrophage type; and burst-forming units of
      erythrocytic type. The SOD groups recovered, respectively, 5.6, 5.3, 4.6, and 4.4
      times as many colonies as the control group. This study demonstrates that the
      addition of SOD to hypothermic storage media may increase the recovery of
      hemopoietic stem cells.

PMID- 9917355
TI  - Abstracts of papers presented at the thirty-fifth annual meeting of the society
      for cryobiology 

PMID- 9917356
TI  - Cumulative subject index for volumes 36-37 

PMID- 9917357
TI  - Induction of germinal vesicle breakdown in a cell-free preparation from starfish
      oocytes.
AB  - Incubation of isolated germinal vesicles in the homogenate from maturing starfish
      oocytes resulted in synchronous germinal vesicle breakdown (GVBD), and chromosome
      condensation and gathering within 30 min. GVBD in this cell-free system required
      aerobic conditions. The endogenous ATP-generation system was preserved in the
      homogenate and effective under aerobic conditions, and thus exogenous ATP was not
      added to the homogenate. Injection of the homogenate into immature starfish
      oocytes induced meiotic maturation without 1-methyladenine, indicating high
      activity of maturation-promoting factor (MPF) in the homogenate. MPF activity in
      the homogenate was stable for 2 h at room temperature, while it disappeared
      within 1 h in the supernatant prepared by centrifugation of the homogenate. This
      disappearance of MPF activity is regulated by cyclin B destruction, similar to
      that seen in vivo.

PMID- 9917358
TI  - The neurotransmitter noradrenaline drives noggin-expressing ectoderm cells to
      activate N-tubulin and become neurons.
AB  - Neurotransmitters regulate neuronal function in the nervous system and modulation
      of their synthesis, release, and binding by immature neurons and their targets is
      a major part of nervous system development. We propose that the neurotransmitter
      noradrenaline regulates neuronal fate during neurulation, before neurons have
      differentiated. The ability of noradrenaline to induce a neural fate was tested
      in naive ectoderm caps cut from late blastula stage Xenopus embryos.
      Noradrenaline (10(-6) M) did not switch on otx-2 or NCAM and did not induce the
      formation of cement glands. We conclude that noradrenaline cannot induce a neural
      fate. By contrast, 10(-8) M noradrenaline activated N-tubulin in ectoderm caps
      expressing the neural inducing molecule noggin by the time intact siblings had
      become mid-neurulae. Methoxamine, a specific alpha-adrenergic receptor agonist,
      also activated N-tubulin in noggin-expressing caps. The alpha-adrenergic receptor
      blocker prazosin inhibited both noradrenaline- and methoxamine-induced activation
      of N-tubulin. The neurotransmitters dopamine and 5-HT did not activate expression
      of N-tubulin. XA-1, Otx-2, X-Delta, and Xotch transcripts were not sensitive to
      noradrenaline. HoxB9, which indicates posteriorization, was not activated by
      noradrenaline. When intact siblings were at stage 27, many cells in noggin
      expressing, noradrenaline-treated caps were stained by the neuron-specific
      mcAb3A10. We propose that noradrenaline is an important endogenous modulator of
      neuronal fate, driving noggin-expressing cells to become neurons by binding to
      alpha-adrenergic receptors and activating a cascade that culminates in the
      expression of the neuronal markers N-tubulin and 3A10.

PMID- 9917359
TI  - Evolutionary alteration in anterior patterning: otx2 expression in the direct
      developing frog Eleutherodactylus coqui.
AB  - The homeobox gene otx2 is a key regulator for specifying the rostral part of the
      vertebrate head. In Xenopus, otx2 directly controls the differentiation of the
      cement gland, the anterior-most organ formed in the tadpole. Since embryos of a
      direct developing frog, Eleutherodactylus coqui, lack a cement gland, we are
      interested in whether altered expression of the otx2 gene is involved in this
      evolutionary change. We have cloned the E. coqui homologue of otx2, Ecotx2. The
      homeodomain of the Ecotx2 protein is identical to the mouse and zebrafish Otx2
      proteins and differs by a single amino acid from the Xenopus Otx2 protein. Study
      of the spatiotemporal expression pattern shows that Ecotx2 RNA is progressively
      restricted to the anterior region of the embryo during gastrulation and becomes
      further restricted to the future forebrain and midbrain during neural
      development. In Xenopus, in addition to the conserved expression in the anterior
      neuroectoderm, the expression in ectoderm expands more anteriorly to the cement
      gland primordium. This anterior expansion of otx2 expression is not found in E.
      coqui, correlating with the loss of a cement gland. When misexpressed in Xenopus
      laevis ectoderm, Ecotx2 can activate expression of the cement-gland-specific
      genes XCG and XAG1, indicating that the function of activating the pathway of
      cement gland formation is retained by the Ecotx2 protein. Our results indicate
      that there are modifications in the pathway of cement gland formation, upstream
      of otx2 expression, in the development of E. coqui.

PMID- 9917360
TI  - A Caenorhabditis elegans homologue of hunchback is required for late stages of
      development but not early embryonic patterning.
AB  - We have cloned a Caenorhabditis elegans homologue of the Drosophila gap gene
      hunchback (hb) and have designated it hbl-1 (hunchback-like). hbl-1 encodes a
      predicted 982-amino-acid protein, containing two putative zinc-finger domains
      similar to those of Drosophila Hunchback. The gene is transcribed embryonically,
      but unlike the maternally expressed Drosophila hb, its mRNA is not detected in C.
      elegans oocytes. A hbl-1::gfp reporter is expressed primarily in ectodermal cells
      during embryonic and larval development. Double-stranded RNA-interference (RNAi)
      was used to indicate hbl-1 loss-of-function phenotypes. Progeny of hbl-1(RNAi)
      hermaphrodites exhibit a range of defects; the most severely affected progeny
      arrest as partially elongated embryos or as hatching, misshapen L1 larvae.
      Animals that survive to adulthood exhibit variably dumpy (Dpy), uncoordinated
      (Unc), and egg-laying defective (Egl) phenotypes, as well as defects in vulval
      morphology (Pvl). Abnormal organization of hypodermal cells and expression of a
      hypodermal marker in hbl-1(RNAi) animals suggests that most of the phenotypes
      observed could be due to improper specification of hypodermal cells. The pattern
      of hbl-1 expression is similar to that reported for the leech hunchback homologue
      Lzf-2, suggesting that these proteins may have similar biological functions in
      diverse species with cellular embryos.

PMID- 9917361
TI  - The role of star in the production of an activated ligand for the EGF receptor
      signaling pathway.
AB  - The Star gene is a member of the EGFR signaling pathway which has diverse
      functions throughout Drosophila development. In order to investigate the protein
      distribution for Star, we have generated a polyclonal antibody. Here, we show
      that the Star protein is expressed perinuclearly in the early female germline and
      later is found in the oocyte cytoplasm. Star is expressed at low levels in other
      tissues. The subcellular localization of the protein has been determined when
      Star is overexpressed in the eye disc. Star is located in the nuclear and
      contiguous endoplasmic reticulum membranes. A functional assay in the wing disc
      demonstrates that Star expression can activate a nonprocessed membrane-bound form
      of the EGFR ligand Spitz and overexpression of Star in the eye disc promotes the
      formation of smaller Spitz proteins. Based on these results, we propose that the
      Star protein is likely to be involved in Spitz ligand processing.

PMID- 9917362
TI  - Msx2 gene dosage influences the number of proliferative osteogenic cells in
      growth centers of the developing murine skull: a possible mechanism for MSX2
      mediated craniosynostosis in humans.
AB  - Throughout its complex morphogenesis, the vertebrate skull must at once protect
      the brain and expand to accommodate its growth. A key structural adaptation that
      allows this dual role is the separation of the bony plates of the skull with
      sutures, fibrous joints that serve as growth centers and allow the calvarial
      bones to expand as the brain enlarges. Craniosynostosis, the premature fusion of
      one or more calvarial bones with consequent abnormalities in skull shape, is a
      common developmental anomaly that disrupts this process. We found previously that
      a single amino acid substitution in the homeodomain of the human MSX2 gene is
      associated with the autosomal dominant disorder craniosynostosis, Boston type.
      This mutation enhances the affinity of Msx2 for its target sequence, suggesting
      that the mutation acts by a dominant positive mechanism. Consistent with this
      prediction, we showed that general overexpression of Msx2 under the control of
      the broadly expressed CMV promoter causes the calvarial bones to invade the
      sagittal suture. Here we use tissue-specific overexpression of Msx2 within the
      calvarial sutures to address the developmental mechanisms of craniosynostosis and
      skull morphogenesis. We demonstrate that a segment of the Msx2 promoter directs
      reporter gene expression to subsets of cells within the sutures. In late
      embryonic and neonatal stages, this promoter is expressed in undifferentiated
      mesenchymal cells medial to the growing bone. By P4, promoter activity is reduced
      in the suture, exhibiting a punctate pattern in undifferentiated osteoblastic
      cells in the outer margin of the osteogenic front. Overexpression of Msx2 under
      the control of this promoter is sufficient to enhance parietal bone growth into
      the sagittal suture by P6. This phenotype is preceded by an increase in both the
      number and the BrdU labeling of osteoblastic cells in the osteogenic fronts of
      the calvarial bones. These findings suggest that an important early event in MSX2
      mediated craniosynostosis in humans is a transient retardation of osteogenic cell
      differentiation in the suture and a consequent increase in the pool of osteogenic
      cells.

PMID- 9917363
TI  - XMAP230 is required for the organization of cortical microtubules and patterning
      of the dorsoventral axis in fertilized Xenopus eggs.
AB  - The dorsoventral axis of Xenopus embryos is specified by a rotation of the egg
      cortex relative to the underlying yolky cytoplasm. This cortical rotation, which
      occurs during the first cell cycle after fertilization, is dependent upon an
      array of parallel microtubules in the subcortical cytoplasm. We have used
      confocal immunofluorescent microscopy and microinjection of affinity-purified
      anti-XMAP230 antibody to address the role of XMAP230, one of three high-molecular
      weight microtubule-associated proteins (MAPs) in Xenopus eggs, in the assembly
      and organization of the cortical microtubule array and specification of the
      dorsoventral axis. Confocal immunofluorescence microscopy revealed that XMAP230
      was associated with cortical microtubules shortly after their appearance in the
      subcortical cytoplasm. XMAP230 staining became more prominent as microtubules
      were aligned and bundled during the cortical rotation. Loss of XMAP230 appeared
      to precede disassembly of cortical microtubules at the end of the first cell
      cycle. Deeper within the cytoplasm, XMAP230 was associated with microtubules
      early in the assembly of the sperm aster. However, later in the first cell cycle,
      XMAP230 was associated with microtubules (MTs) of the first mitotic spindle,
      spindle asters, and the cortical MTs, but not with microtubule remnants of the
      sperm aster. Microinjection of anti-XMAP230 antibody locally disrupted the
      assembly and organization of microtubules in the cortex of activated or
      fertilized eggs and resulted in defects in the dorsoventral patterning of
      embryos. These results indicate that the assembly and/or organization of cortical
      microtubules in fertilized Xenopus eggs and subsequent specification of the
      dorsoventral axis are dependent upon XMAP230.

PMID- 9917364
TI  - Mastermind acts downstream of notch to specify neuronal cell fates in the
      Drosophila central nervous system.
AB  - In the Drosophila central nervous system, cellular diversity is generated through
      the asymmetric partitioning of cell fate determinants at cell division. Neural
      precursors (or neuroblasts) divide in a stem cell lineage to generate a series of
      ganglion mother cells, each of which divides once to produce a pair of
      postmitotic neurons or glial cells. An exception to this rule is the MP2
      neuroblast, which divides only once to generate two neurons. We screened for
      genes expressed in the MP2 neuroblast and its progeny as a means of identifying
      the factors that specify cell fate in the MP2 lineage. We identified a P-element
      insertion line that expresses the reporter gene, tau-beta-galactosidase, in the
      MP2 precursor and its progeny, the vMP2 and dMP2 neurons. The transposon disrupts
      the neurogenic gene, mastermind, but does not lead to neural hyperplasia.
      However, the vMP2 neuron is transformed into its sibling cell, dMP2. By contrast,
      expression of a dominant activated form of the Notch receptor in the MP2 lineage
      transforms dMP2 to vMP2. Notch signalling requires Mastermind, suggesting that
      Mastermind acts downstream of Notch to determine the vMP2 cell fate. We show that
      Mastermind plays a similar role in the neurons derived from ganglion mother cells
      1-1a and 4-2a, where it specifies the pCC and RP2sib fates, respectively. This
      suggests that Notch signalling through Mastermind plays a wider role in
      specifying neuronal identity in the Drosophila central nervous system.

PMID- 9917365
TI  - FGF is required for posterior neural patterning but not for neural induction.
AB  - Fibroblast growth factor (FGF) has been implicated in a variety of developmental
      processes including posterior mesoderm and neural patterning. Previous work has
      led to contradictory roles for FGF in neural induction and anteroposterior neural
      patterning. Launay et al. (Development 122, 869-880, 1996) suggested a
      requirement for FGF in anterior neural induction. In contrast, Kroll and Amaya
      (Development 122, 3173-3183, 1996) and Bang et al. (Development 124, 2075-2085,
      1997) proposed that FGF is not required for early neural patterning. Here we use
      a loss-of-function assay to examine whether FGF is required for neural patterning
      in three experimental situations: (i) in Xenopus early embryos, (ii) in embryonic
      explants consisting of presumptive dorsal mesoderm and neurectoderm (Keller
      explants), and (iii) in explants of dorsal ectoderm and posterior mesoderm in
      which FGF signaling is specifically blocked in the ectoderm. When cultured until
      tailbud stages, Keller explants develop neural tissue with normal anteroposterior
      pattern. Overexpression of the dominant-negative FGF receptor (XFD) in Keller
      explants inhibited the posterior neural markers En-2, Krox-20, and HoxB9, but not
      the panneural marker nrp-1 and the anterior neurectodermal markers XAG-1 and Xotx
      2. Similar results were seen in whole embryos, but only when XFD RNA was targeted
      to both the dorsal and lateral regions. In contrast, addition of FGF to Keller
      explants resulted in a shift of the midbrain-hindbrain boundary marker En-2 to a
      more anterior position normally fated to become cement gland. We also determined
      whether FGF is required specifically by the neurectoderm for anteroposterior
      neural patterning. Recombinants of dorsal ectoderm and posterior mesoderm were
      made in which FGF was specifically blocked in the ectoderm. Spinal cord and
      hindbrain markers were inhibited in these recombinants, whereas anterior markers
      and cement gland development were enhanced. Our results demonstrate that FGF is
      important for posterior development in both mesoderm and neurectoderm and that
      neural induction and posteriorization represent separable developmental events.

PMID- 9917368
TI  - Volume 180, number 1 (1996), in article no. 0344, "biparous: A novel bHLH gene
      expressed in neuronal and glial precursors in Drosophila," by andrew bush,
      yasushi hiromi, and michael cole, pages 759-772 

PMID- 9917367
TI  - A role for Rho-like GTPases in the polarisation of mouse eight-cell blastomeres.
AB  - Polarisation of cells during mouse preimplantation development first occurs
      within blastomeres at the eight-cell stage, as part of a process called
      compaction. Cell-cell contact mediated by the cell adhesion molecule uvomorulin
      (E-cadherin) and the activity of the microfilament cytoskeleton are important in
      the development of compaction, which is crucial for establishment of trophoblast
      and pluriblast (inner cell mass) lineages and for subsequent development. Members
      of the Rho family of p21 GTPases have been shown to regulate the organisation of
      the actin cytoskeleton and adhesion in other cell types. The potential role of
      these proteins in compaction was investigated. Inhibition of Rho with Clostridium
      botulinum C3-transferase disturbed intercellular flattening at compaction and
      prevented cytocortical microfilament polarisation of eight-cell blastomeres, in
      contrast to cytochalasin D which inhibited only adhesion. Microinjection of a
      constitutively activated recombinant Rho protein into four-cell blastomeres
      induced cortical microfilament disruption and apical displacement of nuclei
      associated with polarised clustering of microtubules. Interblastomere adhesion
      was reduced and E-cadherin was aberrently clustered at remaining cell-cell
      contacts. Similarly, activated Cdc42 protein induced nuclear displacement with
      additional cytoplasmic actin bundle formation between nucleus and cell-cell
      contacts. The effects produced by both of the activated GTPase proteins are
      indicative of prematurely induced but aberrently organised polarity. These
      results suggest that Rho family GTPases are involved in the polarisation of early
      mouse blastomeres.

PMID- 9917366
TI  - Heterogeneity of neural progenitor cells revealed by enhancers in the nestin
      gene.
AB  - Using transgenic embryos, we have identified two distinct CNS progenitor cell
      specific enhancers, each requiring the cooperation of at least two independent
      regulatory sites, within the second intron of the rat nestin gene. One enhancer
      is active throughout the developing CNS, while the other is specifically active
      in the ventral midbrain. These experiments demonstrate that neural progenitor
      cells in the midbrain constitute a unique subpopulation based upon their ability
      to activate the midbrain regulatory element. Our finding of differential enhancer
      activity from a gene encoding a structural protein reveals a previously
      unrecognized diversity in neural progenitor cell populations.

PMID- 9917369
TI  - Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis.
AB  - Heterotrimeric G proteins act as signal transducers that couple cell-surface
      receptors to cytoplasmic effector proteins. In fungi, G proteins play essential
      roles during sexual and pathogenic development. They are part of the pheromone
      signaling cascade in both ascomycetes and basidiomycetes, which is crucial for
      the recognition and fusion of cells of opposite mating type. In addition, G
      proteins affect a number of developmental and morphogenetic processes which
      determine the virulence of plant and human fungal pathogens. Cloning and targeted
      disruption of genes encoding alpha subunits of G proteins allowed the attribution
      of specific functions to these signal transducing molecules. Several lines of
      evidence indicate that many of the known fungal G proteins influence the
      intracellular level of cAMP by either stimulating or inhibiting adenylyl cyclase.

PMID- 9917370
TI  - Gibberellin biosynthetic pathway in Gibberella fujikuroi: evidence for a gene
      cluster.
AB  - Differential screening of a Gibberella fujikuroi cDNA library was used to
      successfully clone and identify genes involved in the pathway of gibberellin
      biosynthesis. Several cDNA clones that hybridized preferentially to a cDNA probe
      prepared from mycelium induced for gibberellin production were isolated and
      characterized. The deduced amino acid sequences of two (identical) clones
      contained the conserved heme-binding motif of cytochrome P450 monooxygenases
      (FXXGXXXCXG). One of these cDNA fragments was used as a homologous probe for the
      screening of a genomic library. A hybridizing 6.7-kb genomic SalI fragment was
      cloned into pUC19. The sequencing of this clone revealed that a second cytochrome
      P450 monooxygenase gene was closely linked to the first one. Since at least four
      cytochrome P450 monooxygenase-catalyzed steps are involved in the synthesis of
      gibberellins, chromosome walking was performed to find a further gene of this
      family or other genes involved in gibberellin pathway. Next to the two P450
      monooxygenase genes, a putative geranylgeranyl diphosphate synthase gene, the
      copalyl diphosphate synthase gene, which is the first specific gene of the
      gibberellin pathway, and a third P450 monooxygenase gene were identified. These
      results suggest that at least some of the genes involved in the biosynthesis of
      gibberellins are closely linked in a gene cluster in G. fujikuroi, as has been
      recently found for other "dispensable" pathways in fungi.

PMID- 9917371
TI  - Intra- and interspecies virus transfer in Aspergilli via protoplast fusion.
AB  - Intra- and interspecies transfer of dsRNA viruses between black Aspergilli and
      Aspergillus nidulans strains has been investigated using protoplast fusion. We
      found interspecies transfer of virus in all combinations of black Aspergillus and
      A. nidulans strains and vice versa. Using the same conditions, intraspecies virus
      transfer among heterokaryon incompatible strains was also tested. Whereas such
      transfer was always found among A. nidulans strains, transfer among black
      Aspergilli was frequently unsuccessful. The lack of virus transfer between black
      Aspergillus isolates was further investigated by using a mitochondrial oligomycin
      resistance marker as a positive control for cytoplasmic exchange. These
      experiments showed independent transfer of the oligomycin resistance and dsRNA
      viruses during protoplast fusion of heterokaryon incompatible black Aspergilli.
      The inefficient transfer of dsRNA viruses between black Aspergilli is not caused
      by absolute resistance to viruses but may be related to heterokaryon
      incompatibility reactions that operate intraspecifically. Consequences for the
      dynamics of mycoviruses in populations of black Aspergilli are discussed.

PMID- 9917373
TI  - Mutants of phycomyces with decreased gallic acid content.
AB  - Most plants and some fungi accumulate phenols. Two hydroxybenzoic acids, gallic
      and protocatechuic acids, are abundant in the giant sporangiophores of the
      zygomycete Phycomyces blakesleeanus, much more so than in the basal mycelium or
      the culture medium. The actual concentrations vary with illumination, age of the
      culture, and composition of the medium. We devised a simple screening procedure
      to isolate hba mutants whose sporangiophores contained less gallic acid than the
      wild type. The most useful mutant had very low concentrations of hydroxybenzoic
      acids in the sporangiophores, but about the same as the wild type in the basal
      mycelium and the medium. The mutant was only slightly different from the wild
      type in growth and morphology. Mutant and wild-type sporangiophores grew away
      from ultraviolet C sources (260 nm) equally well. Contrary to previous
      conjectures, ultraviolet tropism does not depend on the ultraviolet absorption of
      gallic acid or other free hydroxybenzoic acids in the sporangiophore. Against
      expectations, phenols did not impair DNA extraction: sporangiophores produced
      better DNA preparations than basal mycelia and the hba mutant only slightly
      better than the wild type.

PMID- 9917375
TI  - Cumulative subject index volumes 23-25 

PMID- 9917372
TI  - Genome size determination in peronosporales (Oomycota) by Feulgen image analysis.
AB  - Genome size was determined, by nuclear Feulgen staining and image analysis, in 46
      accessions of 31 species of Peronosporales (Oomycota), including important plant
      pathogens such as Bremia lactucae, Plasmopara viticola, Pseudoperonospora
      cubensis, and Pseudoperonospora humuli. The 1C DNA contents ranged from 0.046
      (45. 6 Mb) to 0.163 pg (159.9 Mb). This is 0.041- to 0.144-fold that of Glycine
      max (soybean, 1C = 1.134 pg), which was used as an internal standard for genome
      size determination. The linearity of Feulgen absorbance photometry method over
      this range was demonstrated by calibration of Aspergillus species (1C = 31-38 Mb)
      against Glycine, which revealed differences of less than 6% compared to the
      published CHEF data. The low coefficients of variation (usually between 5 and
      10%), repeatability of the results, and compatibility with CHEF data prove the
      resolution power of Feulgen image analysis. The applicability and limitations of
      Feulgen photometry are discussed in relation to other methods of genome size
      determination (CHEF gel electrophoresis, reassociation kinetics, genomic
      reconstruction) that have been previously applied to Oomycota.

PMID- 9917376
TI  - Cumulative organism index volumes 23-25 

PMID- 9917374
TI  - Functional characteristics of pyruvate transport in Phycomyces blakesleeanus.
AB  - A saturable and accumulative transport system for pyruvate has been detected in
      Phycomyces blakesleeanus NRRL 1555(-) mycelium. It was strongly inhibited by
      alpha-cyano-4-hydroxycinnamate. l-Lactate and acetate were competitive inhibitors
      of pyruvate transport. The initial pyruvate uptake velocity and accumulation
      ratio was dependent on the external pH. The Vmax of transport greatly decreased
      with increasing pH, whereas the affinity of the carrier for pyruvate was not
      affected. The pyruvate transport system mediated its homologous exchange, which
      was essentially pH independent, and efflux, which increased with increasing
      external pH. The uptake of pyruvate was energy dependent and was strongly
      inhibited by inhibitors of oxidative phosphorylation and of the formation of
      proton gradients. Glucose counteracted the inhibitory effect of the pyruvate
      transport produced by inhibitors of mitochondrial ATP synthesis. Our results are
      consistent with a pyruvate/proton cotransport in P. blakesleeanus probably driven
      by an electrochemical gradient of H+ generated by a plasma membrane H+-ATPase.

PMID- 9917377
TI  - Cross-linking localization of a HIV-1 reverse transcriptase peptide involved in
      the binding of primer tRNALys3.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) initiates
      the synthesis of DNA from the 3' end of its specific primer, tRNALys3. The
      regions of tRNALys3 in close contact with RT are well known, while a precise
      knowledge of the RT regions interacting with tRNALys3 is not yet available. To
      address this question we cross-linked the heterodimeric p66/p51 RT to tRNALys3
      using cis-aquahydroxydiammino-platinum. Ribonucleoprotein complexes of molecular
      masses higher than the p66 subunit were obtained. After RNase A digestion of the
      RT-tRNA complex, a labeled oligoribonucleotide (ORN) was mainly found associated
      to the p66 subunit. This labeled p66-ORN complex was then proteolyzed with
      Staphylococcus aureus V8 protease. A highly purified radioactive peptide was
      obtained after two chromatographic purification steps. Its N-terminal sequence
      corresponded with amino acid residues 241VQPI244. Using the crystallographic
      structure of HIV-1 RT, this peptide was localized at the beta14-sheet end, near
      to the hairpin formed by beta12 and beta13-sheets ("primer grip") and the alphaH
      helix. The so called "VQPI peptide" is in the border of the thumb and the palm
      subdomains of the p66 subunit. This study palliates the absence of a three-
      dimensional structure of the RT-tRNA complex and led to a peptide in interaction
      with tRNALys3 present in all HIV-1 RT isolates.

PMID- 9917378
TI  - Voltage and pH-induced channel closure of porin OmpF visualized by atomic force
      microscopy.
AB  - Gram-negative bacteria are protected by an outer membrane in which trimeric
      channels, the porins, facilitate the passage of small solutes. The pores are
      formed by membrane-spanning antiparallel beta-strands, which are connected by
      short turns on the periplasmic side and long loops on the extracellular side.
      Voltage and pH-dependent conformational changes of these extracellular loops have
      now been visualized by atomic force microscopy of two-dimensional crystals of
      Escherichia coli porin OmpF. The observed conformational changes accompany the
      closure of the channel entrance, and suggest that this is a mechanism that the
      cells have evolved to protect themselves from drastic changes of the environment.

PMID- 9917379
TI  - Fold prediction and evolutionary analysis of the POZ domain: structural and
      evolutionary relationship with the potassium channel tetramerization domain.
AB  - Using iterative database searches, a statistically significant sequence
      similarity was detected between the POZ (poxvirus and zinc finger) domains found
      in a variety of proteins involved in animal transcription regulation,
      cytoskeleton organization, and development, and the tetramerization domain of
      animal potassium channels. Using the crystal structure of the Aplysia Shaker
      channel tetramerization domain as a template, the common structure of the POZ
      domain class was predicted. Examination of the structure resulted in the
      identification of several structural features and specific amino acid residues
      that may be involved in conserved protein-protein interactions mediated by the
      POZ domains as well as those that may contribute to the specificity of these
      interactions. Phylogenetic analysis of the POZ domains suggests that the common
      ancestor of the crown group eukaryotes already possessed this domain; POZ domains
      have undergone independent expansion in plants and in different animal lineages.

PMID- 9917380
TI  - Folding of amphipathic alpha-helices on membranes: energetics of helix formation
      by melittin.
AB  - Membranes have a potent ability to promote secondary structure formation in a
      wide range of membrane-active peptides, believed to be due to a reduction through
      hydrogen bonding of the energetic cost of partitioning peptide bonds. This
      process is of fundamental importance for understanding the mechanism of action of
      toxins and antimicrobial peptides and the stability of membrane proteins. A
      classic example of membrane-induced folding is the bee-venom peptide melittin
      that is largely unstructured when free in solution, but strongly adopts an
      amphipathic alpha-helical conformation when partitioned into membranes. We have
      determined the energetics of melittin helix formation through measurements of the
      partitioning free energies and the helicities of native melittin and of a
      diastereomeric analog with four d-amino acids (d4,l-melittin). Because D4,l
      melittin has little secondary structure in either the free or bound forms, it
      serves as a model for the experimentally inaccessible unfolded bound form of
      native melittin. The partitioning of native melittin into large unilamellar
      phosphocholine vesicles is 5.0(+/-0.7) kcal mol-1 more favorable than the
      partitioning of d4,l-melittin (1 cal=4.186 J). Differences in the circular
      dichroism spectra of the two forms of melittin indicate that bound native
      melittin is more helical than bound d4, l-melittin by about 12 residues. These
      findings disclose that the free energy reduction per residue accompanying the
      folding of melittin in membrane interfaces is about 0.4 kcal mol-1, consistent
      with the hypothesis that hydrogen bonding reduces the high cost of partitioning
      peptide bonds. A value of 0.6 kcal mol-1 per residue has been observed for beta
      sheet formation by a hexapeptide model system. These two values provide a useful
      rule of thumb for estimating the energetic consequences of membrane-induced
      secondary structure formation.

PMID- 9917381
TI  - Native proteins are surface-molten solids: application of the Lindemann criterion
      for the solid versus liquid state.
AB  - Since the internal motions of proteins play an essential role in their biological
      function, it is important to characterize them in a fundamental way. The
      Lindemann criterion for the solid state is applied to molecular dynamics
      simulations and temperature-dependent X-ray diffraction data of proteins. It is
      found that the interior of native proteins is solid-like, while their surface is
      liquid-like. When the entire protein becomes solid-like at low temperature (
      approximately 220 K), the protein is inactive. Thus, the surface-molten solid
      nature of proteins in their native state permits the dynamics required for
      function, while preserving their stability. Comparison with rare gas clusters and
      polymer models indicates that their thermodynamic phase diagrams have many
      elements in common with those of proteins.

PMID- 9917382
TI  - Protein surface roughness and small molecular binding sites.
AB  - Pharmaceutical design is usually directed at developing small molecules that can
      specifically bind and alter the activity of a target protein. Here, we show that
      high-affinity binding of small molecules requires a rough patch on a protein
      surface. Drug design strategies should therefore be targeted to rough areas on a
      protein. Our results indicate that the roughness of small functional sites may
      reflect the complex local shapes needed to fit specific interactions into small
      areas.

PMID- 9917383
TI  - Functional analysis of hemoglobin molecules locked in doubly liganded
      conformations.
AB  - A controversy still exists over whether the molecular basis of hemoglobin
      cooperativity can be more appropriately explained by one of two classic
      allosteric models, the concerted and sequential models. To distinguish these two
      models from the viewpoint of their fundamental processes, namely, the presence or
      absence of conformational equilibria, we have trapped the conformations of
      nickel(II)-iron(II) hybrid hemoglobin molecules with two CO-bound, alpha2(Fe
      CO)beta2(Ni) and alpha2(Ni)beta2(Fe-CO), by encapsulation in the water-filled
      pores of sol-gel-derived transparent silica-gels. In our experimental system,
      nickel(II) protoporphyrin binds neither O2 nor CO and mimics a fixed deoxyheme,
      and the gel matrix provides a means of inhibiting large-scale protein structural
      changes, thus enabling O2 equilibrium study of the hybrids still in their doubly
      liganded conformations. Results showed that two conformations of widely different
      O2 affinity exist together in each doubly liganded hemoglobin, providing a direct
      proof of the concerted mechanism versus the sequential mechanism.

PMID- 9917384
TI  - The TATA-binding protein from Saccharomyces cerevisiae oligomerizes in solution
      at micromolar concentrations to form tetramers and octamers.
AB  - Equilibrium analytical ultracentrifugation has been used to determine the
      stoichiometry and energetics of the self-assembly of the TATA-binding protein of
      Saccharomyces cerevisiae at 30 degreesC, in buffers ranging in salt concentration
      from 60 mM KCl to 1 M KCl. The data are consistent with a sequential association
      model in which monomers are in equilibrium with tetramers and octamers at protein
      concentrations above 2.6 microM. Association is highly cooperative, with octamer
      formation favored by approximately 7 kcal/mol over tetramers. At high [KCl], the
      concentration of tetramers becomes negligible and the data are best described by
      a monomer-octamer reaction mechanism. The equilibrium association constants for
      both monomer <--> tetramer and tetramer <--> octamer reactions change with [KCl]
      in a biphasic manner, decreasing with increasing [KCl] from 60 mM to 300 mM, and
      increasing with increasing [KCl] from 300 mM to 1 M. At low [KCl], approximately
      3 mole equivalents of ions are released at each association step, while at high
      [KCl], approximately 3 mole equivalents of ions are taken up at each association
      step. These results suggest that there is a salt concentration-dependent change
      in the assembly mechanism, and that the mechanistic switch takes place near 300
      mM KCl. The possibility that this self-association reaction may play a role in
      the activity of the TATA-binding protein in vivo is discussed.

PMID- 9917385
TI  - Toxin-antitoxin systems homologous with relBE of Escherichia coli plasmid P307
      are ubiquitous in prokaryotes.
AB  - Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes specify two
      proteins, a cytotoxin and an antitoxin. The antitoxins neutralize the cognate
      toxins by forming tight complexes with them. The antitoxins are unstable due to
      degradation by cellular proteases (Lon or Clp), whereas the toxins are stable.
      Here we show that orf7 (denoted relBP307) and orf6 (denoted relEP307) of
      Escherichia coli plasmid P307 are homologous to the relBE genes of E. coli and
      constitute a two-component toxin-antitoxin system: (i) relEP307 encodes a
      cytotoxin lethal or inhibitory to host cells; (ii) relBP307 encodes an antitoxin
      that prevents the lethal action of the relE-encoded toxin; (iii) RelBP307
      antitoxin is degraded by Lon protease; (iv) RelBP307 antitoxin autoregulates the
      relBE operon of P307 at the level of transcription; (v) RelEP307 toxin acts as a
      co-repressor of transcription; and (vi) the relBE system stabilizes a mini-P307
      replicon by the killing of plasmid-free cells. Using database searching, we found
      relBE homologues on the chromosomes of many Gram-negative and Gram-positive
      bacteria. Even more surprising, numerous relBE-homologous gene systems are
      present on the chromosomes of Archae. Thus, toxin-antitoxin systems homologous
      with relBE of E. coli are ubiquitous in prokaryotic organisms.

PMID- 9917386
TI  - A polyadenylylation-specific RNA-contact site on the surface of the bifunctional
      vaccinia virus RNA modifying protein VP39 that is distinct from the mRNA 5' end
      binding "cleft".
AB  - VP39 is a bifunctional mRNA-modifying protein that acts as both an mRNA cap
      specific 2'-O-methyltransferase and a processivity factor for VP55, the vaccinia
      poly(A) polymerase catalytic subunit. Although regions of the protein surface
      required for methyltransferase function are well defined, it has been unclear
      whether the protein polyadenylylation function requires direct RNA contact and,
      if so, where the contact site(s) might be located on the protein surface. Here,
      we show that the VP55-VP39 heterodimer forms a stable complex with a 50mer
      oligonucleotide bearing a U2-N25-U motif, as opposed to the U2-N15-U motif that
      is optimal for stable complex formation with VP55 alone. An oligonucleotide
      bearing a U2-N25-U motif in which the downstream U residue is replaced with
      4thioU can be efficiently photocrosslinked to VP39, but only in the context of
      the VP55-VP39 heterodimer. By partial proteolysis of end-labeled VP39, the site
      of oligonucleotide photocrosslinking was localized to the region of VP39 between
      residues Lys90 and Arg122. Peptide microsequencing and confirmatory mutagenesis
      identified the side-chain of Arg107 as the photocrosslinking site. Substitution
      of this residue with lysine abolished photocrosslinking entirely, consistent with
      the established RNA binding role of arginine in other RNA-binding proteins. This
      study provides clear evidence for a polyadenylylation-specific RNA-contact site
      on the surface of VP39, which is distinct from the RNA-binding methyltransferase
      "cleft" characterized in recent crystallographic and biochemical studies.

PMID- 9917387
TI  - The RNA polymerase III-recruiting factor TFIIIB induces a DNA bend between the
      TATA box and the transcriptional start site.
AB  - TFIIIB, the RNA polymerase III-recruiting factor of Saccharomyces cerevisiae, may
      be assembled upstream of the transcriptional start site, either through the
      interaction of its constituent TATA-binding protein (TBP) with a strong TATA-box,
      or by means of the multisubunit assembly factor, TFIIIC. Missing nucleoside
      interference analysis of TFIIIC-dependent TFIIIB-DNA complex formation revealed
      enhanced complex formation at 0 degreesC when the DNA is missing nucleosides in
      two broad 7-10 bp regions centered around base-pairs -17 and -3 relative to the
      transcriptional start site; no effect of missing nucleosides was evident at 20
      degreesC. The implication of these results for required DNA flexure in TFIIIC
      mediated TFIIIB-DNA complex formation was pursued in a TFIIIC-independent
      context, using DNA with a suboptimal 6 bp TATA box (TATAAA). A unique missing
      nucleoside at the downstream end of the TATA box, corresponding to the position
      of one of two TBP-mediated DNA kinks, significantly enhances TBP-DNA complex
      formation. In contrast, TFIIIB displays a broad preference for missing
      nucleosides within an approximately 15 bp region immediately downstream of the
      TATA box. Consecutive mismatches (4-nt loops), either at the sites of TBP
      mediated DNA kinking at both ends of the TATA box or within the identified region
      where missing nucleosides promote TFIIIB-DNA complex formation, also result in
      enhanced and specific TFIIIB assembly; 4-nt loops further downstream do not lead
      to preferential placement of TFIIIB. We conclude that TFIIIB induces an
      additional DNA deformation between the TATA box and the start site of
      transcription that is likely to be more extended than the sharp kinks generated
      by TBP.

PMID- 9917388
TI  - NF-Y binding to twin CCAAT boxes: role of Q-rich domains and histone fold
      helices.
AB  - NF-Y (CBF) is a CCAAT-binding trimer that activates 25 % of eukaryotic promoters.
      It contains putative histone fold motifs (HFMs) and distorts DNA. By using
      electrophoretic mobility shift assays with the twin CCAAT boxes of the human
      gamma-globin promoter and several combinations of subunit mutants, we dissected
      some of the structural features of CCAAT-box binding. NF-YA and NF-YC Q-rich
      domains significantly influence bending angles quantitatively, but not
      qualitatively, since they do not modify DNA orientation. They are both required
      for co-operative interactions among NF-Y molecules: for this, a precise
      alignement of two CCAAT boxes, 32 bp, three turns of the helix, is essential.
      Unlike the wild-type (wt) protein, steric hindrance does not impede simultaneous
      binding of the mutant composed of the short homology domains to CCAAT boxes
      closer than 22 bp: the addition of 11 amino acid residues to NF-YB and 13 to NF
      YC flanking the HFM, restores wt behaviour. These stretches are predicted to form
      H2B-like alphaC and H2A-like alphaN fourth helices. A further support to this
      hypothesis comes from off-rates analysis of mutant combinations: the half-life of
      NF-Y, which is dependent on the type of NF-YB used, is extremely shortened, when
      the putative alphaC is present, nearly as much as in the wt NF-YB. These data (i)
      provide further evidence that NF-YB-NF-YC belong to the H2B-H2A subclasses, (ii)
      uncover new features of Q-rich domains, and (iii) define rules for NF-Y synergy
      that are potentially important for the regulation of many eukaryotic promoters.

PMID- 9917389
TI  - Degradation of FinP antisense RNA from F-like plasmids: the RNA-binding protein,
      FinO, protects FinP from ribonuclease E.
AB  - Transfer of F-like plasmids is regulated by the FinOP system, which controls the
      expression of traJ, a positive regulator of the transfer operon. F FinP is a 79
      base antisense RNA, composed of two stem-loops, complementary to the 5'
      untranslated leader of traJ mRNA. Binding of FinP to the traJ leader sequesters
      the traJ ribosome binding site, preventing its translation and repressing plasmid
      transfer. The FinO protein binds stem-loop II of FinP and traJ mRNA and promotes
      duplex formation in vitro. FinO stabilizes FinP, increasing its effective
      concentration in vivo. To determine how FinO protects FinP from decay, the
      degradation of FinP was examined in a series of ribonuclease-deficient strains.
      Using Northern blot analysis, full-length FinP was found to be stabilized
      sevenfold in an RNase E-deficient strain. The major site of RNase E cleavage was
      mapped on synthetic FinP, to the single-stranded region between stem-loops I and
      II. A secondary site near the 5' end ( approximately 10 bases) was also observed.
      A GST-FinO fusion protein protected FinP from RNase E cleavage at both sites in
      vitro. Two duplexes between FinP and traJ mRNA were detected in an RNase III
      deficient strain. The larger duplex resulted from extension of the FinP
      transcript at its 3' end, suggesting readthrough at the terminator that
      corresponds to FinP stem-loop II. A point mutant of finP (finP305; C30U) that is
      unable to repress traJ in the presence of FinO was also characterized. The
      pattern of RNase E digestion of finP305 RNA differed from FinP, and GST-FinO did
      not protect finP305 RNA from cleavage in vitro. The half-life of finP305 RNA
      decreased more than tenfold in vivo, such that the steady-state levels of finP305
      RNA, in the presence of FinO, were insufficient to significantly reduce the level
      of traJ mRNA available for translation, allowing derepressed levels of transfer.

PMID- 9917390
TI  - Mutations in the conserved P loop perturb the conformation of two structural
      elements in the peptidyl transferase center of 23 S ribosomal RNA.
AB  - Evidence is presented for the participation of the P loop (nucleotides G2250
      C2254) of 23 S rRNA in establishing the tertiary structure of the peptidyl
      transferase center. Single base substitutions were introduced into the P loop,
      which participates in peptide bond formation through direct interaction with the
      CCA end of P site-bound tRNA. These mutations altered the pattern of reactivity
      of RNA to chemical probes in a structural subdomain encompassing the P loop and
      extending roughly from G2238 to A2433. Most of the effects on chemical
      modification in the P loop subdomain occurred near sites of tertiary interactions
      inferred from comparative sequence analysis, indicating that these mutations
      perturb the tertiary structure of this region of RNA. Changes in chemical
      modification were also seen in a subdomain composed of the 2530 loop (nucleotides
      G2529-A2534) and the A loop (nucleotides U2552-C2556), the latter a site of
      interaction with the CCA end of A site-bound tRNA. Mutations in the P loop
      induced effects on chemical modification that were commensurate with the severity
      of their characterized functional defects in peptide bond formation, tRNA binding
      and translational fidelity. These results indicate that, in addition to its
      direct role in peptide bond formation, the P loop contributes to the tertiary
      structure of the peptidyl transferase center and influences the conformation of
      both the acceptor and peptidyl tRNA binding sites.

PMID- 9917391
TI  - Inversion/dimerization of plasmids mediated by inverted repeats.
AB  - In contrast with earlier studies on the lambda and Escherichia coli genomes,
      recombination between inverted repeats on plasmids is highly efficient and shown
      to be recA-independent. In addition, the recombination product is exclusively a
      head-to-head inverted dimer. Here, we show that this recombination/rearrangement
      event can occur on different plasmid replicons and is not specific to the
      particular sequence within the inverted repeats. Transcription readthrough into
      the inverted repeats has little effect on this event. Genetic analysis has also
      indicated that most known recombination enzymes are not involved in this process.
      Specifically, single or double mutants defective in Holliday junction resolution
      systems (RuvABC and/or RecG/RusA) do not abolish this recombination/rearrangement
      event. This result does not support the previous models (i.e. the reciprocal
      strand-switching and the cruciform-dumbbell models) in which intermediates
      containing Holliday junctions are proposed. Further analysis has demonstrated
      that the recombination/rearrangement frequency is dramatically (over 1000-fold)
      reduced if mismatches (2.8 %) are present within the inverted repeats. Mutations
      in dam, mutH and mutL genes partially or completely restored the
      recombination/rearrangement frequency to the level exhibited by the perfect
      inverted repeats, suggesting the formation of heteroduplexes during
      recombination/rearrangement. Sequencing analysis of the
      recombination/rearrangement products have indicated that the majority of the
      products do not involve crossing-over. We discuss a possible mechanism in which
      blockage of the lagging strand polymerase by a hairpin triggers
      recombination/rearrangement mediated by inverted repeats.

PMID- 9917393
TI  - Genetic analysis of the base-specific contacts of BamHI restriction endonuclease.
AB  - Here, we investigate the highly specific interaction of the BamHI endonuclease
      with its cognate recognition sequence GGATCC by determining which amino acid
      residues can be substituted at the DNA interface while maintaining specificity.
      Mutational studies, together with the structural determination of the restriction
      endonuclease BamHI have revealed the amino acid residues which are involved in
      DNA catalysis and those which play a role in the specific binding of the enzyme
      to its cognate DNA recognition sequence. Amino acid residues N116, S118, R122,
      D154 and R155 are involved in DNA sequence recognition and are located in the
      major groove in close proximity to the nucleotide bases comprising the
      recognition sequence. Cassette mutagenesis of these amino acids, together with in
      vivo transcriptional interference selection, was used to identify an array of
      substitutions which maintain site-specific binding to the cognate GGATCC
      sequence. This approach has demonstrated the extent of acceptable variation among
      amino acid residues which are directly involved in site-specific binding. One
      variant, double mutant N116H, S118G was found to cleave DNA only when the adenine
      base in the recognition site is methylated.

PMID- 9917392
TI  - Membrane topology of the Rickettsia prowazekii ATP/ADP translocase revealed by
      novel dual pho-lac reporters.
AB  - Here, we report the construction and characterization of dual reporters,
      consisting of both an Escherichia coli alkaline phosphatase (AP) gene and an
      alpha-fragment of the beta-galactosidase (BG) gene, for studying membrane protein
      topology by the gene fusion approach. Each of the reporters, when fused to
      periplasmic domains of polytopic proteins, produces fusions with high AP activity
      and, when fused to cytoplasmic domains, produces fusions with high BG activity in
      E. coli strains capable of alpha-complementation. The dual nature of these
      reporters simplifies interpretation of data obtained with poorly expressed
      fusions and allows one to evaluate the reliability of topological data.
      Deleterious effects resulting from the cell's attempt to export the full-length
      BG are eliminated in this approach. We describe dual indicator plates that allow
      for discrimination between colonies bearing cytoplasmic fusions, periplasmic
      fusions, and no fusions. We have generated a set of fusions to the topologically
      well-studied lactose permease of E. coli and demonstrated that topological
      information generated by these new reporters is in good agreement with the
      existing model. We used this new methodology for the determination of membrane
      topology of the Rickettsia prowazekii ATP/ADP translocase (Tlc). Our results were
      in agreement with the proposed in silico topological model in which Tlc traverses
      the cytoplasmic membrane of E. coli 12 times with its N and C termini facing the
      cytoplasm.

PMID- 9917394
TI  - A mutant of BamHI restriction endonuclease which requires N6-methyladenine for
      cleavage.
AB  - Amino acid residues Asn116 and Ser118 of the restriction endonuclease BamHI make
      several sequence-specific and water-bridged contacts to the DNA bases. An in vivo
      selection was used to isolate BamHI variants at position 116, 118 and 122 which
      maintained sequence specificity to GGATCC sites. Here, the variants N116H,
      N116H/S118G and S118G were purified and characterized. The variants N116H and
      N116H/S118G were found to have lost their ability to cleave unmethylated GGATCC
      sequences by more than two orders of magnitude, while maintaining nearly wild
      type levels of activity on the N6-methyladenine-containing sequence, GGmATCC. In
      contrast, wild-type BamHI and variant S118G have only a three- to fourfold lower
      activity on unmethylated GGATCC sequences compared with GGmATCC sequences. The
      N116 to H116 mutation has effectively altered the specificity of BamHI from an
      endonuclease which recognizes and cleaves GGATCC and GGmATC, to an endonuclease
      which only cleaves GGmATCC. The N116H change of specificity is due to the lowered
      binding affinity for the unmethylated sequence because of the loss of two
      asparagine-DNA hydrogen bonds and the introduction of a favorable van der Waals
      contact between the imidazole group of histidine and the N6-methyl group of
      adenine.

PMID- 9917396
TI  - Association of kettin with actin in the Z-disc of insect flight muscle.
AB  - The Z-discs of insect muscle contain kettin, a modular protein of 500-700 kDa.
      The Drosophila protein is made up of a chain of immunoglobulin (Ig) domains
      separated by linker sequences. Kettin differs from other modular muscle proteins
      of the Ig superfamily in binding to thin filaments rather than thick filaments.
      Kettin isolated from Lethocerus (waterbug) muscle is an elongated molecule 180 nm
      long, which binds to F-actin with high affinity (Kd=1.2 nM) and a stoichiometry
      of one Ig domain per actin protomer. Competition between kettin and tropomyosin
      for binding to actin excludes tropomyosin from the Z-disc. In contrast, kettin
      and alpha-actinin bind simultaneously to actin, which would reinforce the Z-disc
      lattice. In vitro, kettin promotes the antiparallel association of actin
      filaments, and a similar process may occur in the developing sarcomere: actin
      filaments interdigitate in an antiparallel fashion in the Z-disc with the N
      terminus of kettin within the Z-disc, and the C terminus some way outside. We
      propose a model for the association of kettin with actin in which the molecule
      follows the genetic helix of actin and Ig domains, separated by linker sequences,
      bind to each actin protomer.

PMID- 9917395
TI  - Na+-driven flagellar motor resistant to phenamil, an amiloride analog, caused by
      mutations in putative channel components.
AB  - The rotation of the Na+-driven flagellar motor is specifically and strongly
      inhibited by phenamil, an amiloride analog. Here, we provide the first evidence
      that phenamil interacts directly with the Na+-channel components (PomA and PomB)
      of the motor. The alterations in Mpar (motility resistant to phenamil) strains
      were mapped to the pomA and/or pomB genes. We cloned and sequenced pomA and pomB
      from two Mpar strains, NMB205 and NMB201, and found a substitution in pomA
      (Asp148 to Tyr; NMB205) and in pomB (Pro16 to Ser; NMB201). Both residues are
      predicted to be near the cytoplasmic ends of the putative transmembrane segments.
      Mutational analyses at PomA-Asp148 and PomB-Pro16 suggest that a certain
      structural change around these residues affects the sensitivity of the motor to
      phenamil. Co-expression of the PomA D148Y and PomB P16S proteins resulted in an
      Mpar phenotype which seemed to be less sensitive to phenamil than either of the
      single mutants, although motility was more severely impaired in the absence of
      inhibitors. These results support the idea that PomA and PomB interact with each
      other and suggest that multiple residues, including Asp148 of PomA and Pro16 of
      PomB, constitute a high-affinity phenamil-binding site at the inner face of the
      PomA/PomB channel complex.

PMID- 9917397
TI  - Resolving the discrepancies among nucleic acid conformational analyses.
AB  - Growing interest in understanding the relationship between the global folding of
      nucleic acids and the sequence-dependent structure of individual base-pair steps
      has stimulated the development of new mathematical methods to define the geometry
      of the constituent base-pairs. Several approaches, designed to meet guidelines
      set by the nucleic acid community, permit rigorous comparative analyses of
      different three-dimensional structures, as well as allow for reconstruction of
      chain molecules at the base-pair level. The different computer programs, however,
      yield inconsistent descriptions of chain conformation. Here we report our own
      implementation of seven algorithms used to determine base-pair and dimer step
      parameters. Aside from reproducing the results of individual programs, we uncover
      the reasons why the different algorithms come to conflicting structural
      interpretations. The choice of mathematics has only a limited effect on the
      computed parameters, even in highly deformed duplexes. The results are much more
      sensitive to the choice of reference frame. The disparate schemes yield very
      similar conformational descriptions if the calculations are based on a common
      reference frame. The current positioning of reference frames at the inner and
      outer edges of complementary bases exaggerates the rise at distorted dimer steps,
      and points to the need for a carefully defined conformational standard.

PMID- 9917398
TI  - The 1.8 A crystal structure of a statically disordered 17 base-pair RNA duplex:
      principles of RNA crystal packing and its effect on nucleic acid structure.
AB  - The crystal structure of a 17 base RNA oligomer, r(CACCGGAUG GUUCGGUG), has been
      solved to a resolution of 1.8 A through a combination of molecular replacement,
      multiple isomorphous replacement phasing, and analysis of observed intensity
      distributions. The oligomer, which forms a stem-loop in solution, crystallized as
      a pseudo-infinite duplex in spacegroup P321. The asymmetric unit of the crystal
      contains four superimposed orientations of the duplex that are out of register,
      such that backbones superimpose, but base identity differs. This static disorder
      was initially discovered by brominating a single residue per strand in the
      sequence, and observing four peaks per strand in difference maps phased with a
      native molecular replacement solution. The presence of four superimposed duplex
      "motifs" related by non-crystallographic hypersymmetry was detected by computing
      <I2>/<I>2 and Wilson ratios for the observed intensities. The observed ratios
      matched those produced from calculated intensities of a 4-fold statically
      disordered model. Multi-conformer simulated annealing refinement against a
      maximum-likelihood target incorporating experimental phase information was used
      to refine the 4-fold disordered model to an Rfree and R of 29.35% and 25.5%,
      respectively. The resulting structure reveals four distinct conformations of the
      duplex, with an average pairwise backbone rmsd of 2.35 A. The structural
      differences between the four conformations, which can be attributed to
      differences in packing environment, highlight the possible influence of crystal
      packing forces on nucleic acid X-ray structures. Analysis of inter-helical
      packing between symmetry-related molecules reveals an RNA "zipper" that mediates
      direct phosphate oxygen-2' hydroxyl interactions between close-packed phosphate
      sugar backbones. This may be a general mode for RNA tertiary interaction that
      does not depend on metal ions or primary sequence.

PMID- 9917399
TI  - Evolutionary trace analysis of the Kunitz/BPTI family of proteins: functional
      divergence may have been based on conformational adjustment.
AB  - The structural and functional evolution of the Kunitz/bovine pancreatic trypsin
      inhibitor (BPTI) family of proteins, which includes serine proteinase inhibitors
      and potassium channel blockers, was analysed with the evolutionary trace method.
      This method highlights sites in aligned primary sequences whose side-chain
      variation can be strongly linked with the past development of different
      functional classes or subgroups within the family. A total of 16 such "class
      specific" positions distributed throughout the molecular fold were identified. On
      average, the side-chain chemistry at these positions had been more conserved and
      made greater contribution to molecular stability than the side-chain chemistry at
      remaining sites of variation. It was possible to use these 16 positions to
      describe the division of the Kunitz/BPTI family into general functional classes.
      According to known complexes of inhibitor variants with serine proteinases, only
      two of the 16 class-specific positions appear to be directly involved in
      intermolecular recognition via the "antiproteinase site". Instead, from various
      critical locations in the fold, the remainder seem to have been associated with
      various degrees of intramolecular conformational adjustment to the underlying
      framework of the antiproteinase site. It is, therefore, implied that functional
      diversification in this family has been founded upon both sustained evolutionary
      selection and conformational adjustment. The findings are important for protein
      engineers wishing to alter the binding selectivity of these molecules, because it
      appears that the issue of target recognition is dependent on the conformation of
      the chain segment to which the interactive side-chains are attached. To retarget
      members of this family towards potentially novel peptide binding sites,
      substitutions at certain structurally significant class-specific positions could
      be a good starting point.

PMID- 9917400
TI  - Structural effect of complete [Rp]-phosphorothioate and phosphorodithioate
      substitutions in the DNA strand of a model antisense inhibitor-target RNA
      complex.
AB  - Chemically modified DNA oligonucleotides have been crucial to the success of
      antisense therapeutics. Although such modifications are ubiquitous in the clinic,
      high-resolution structural studies of pharmaceutically relevant derivatives have
      been limited to only a few molecules. We have completed a high-resolution NMR
      structural study of three DNA.RNA hybrids with the sequence d(CCTATAATCC).
      r(GGAUUAUAGG). All hybrids contain an unmodified RNA strand, whereas the DNA
      strand of each hybrid contains one of three different sugar-phosphate backbone
      linkages at each nucleotide: (1) phosphate, (2) [Rp]-phosphorothioate, or (3)
      phosphorodithioate. The UV and NMR melting profiles revealed that the normal
      hybrid is more stable than the [Rp]-phosphorothioate, which in turn is more
      stable than the phosphorodithioate. Homonuclear two-dimensional nuclear
      Overhauser effect spectroscopy and double quantum-filtered correlation
      spectroscopy afforded nearly complete non-labile proton assignments. The three
      molecules show nearly equivalent chemical shifts, with the exception of H3'
      protons, which are shifted downfield in a manner that appears correlated with the
      degree of sulfur substitution at phosphate. All three hybrids exhibit unusually
      broad linewidths for deoxyribose protons H2' and H2".Distance restraints were
      calculated from NOE cross-peak intensities via a complete relaxation matrix
      approach using the program RANDMARDI. Detailed comparison of interproton
      distances from each hybrid indicates that the three molecules share a common
      structure, with neither strand in canonical A or B form. Correlation of R
      factors, calculated using the program CORMA with DNA H2'-base and H3'-base
      distances, revealed a relative increase in the population of B-type sugar
      conformations for deoxyriboses in the A+T-rich center of the hybrid sequence. It
      is widely known that the activity of enzymes which act upon DNA.RNA hybrid
      substrates (e.g. ribonuclease H) is impacted when the hybrids contain
      phosphorothioate or phosphorodithioate substitutions. The structural similarity
      of the three hybrids examined here suggests that factors other than global
      structure may mediate the activity of these enzymes.

PMID- 9917401
TI  - Molecular dynamics studies of axis bending in d(G5-(GA4T4C)2-C5) and d(G5
      (GT4A4C)2-C5): effects of sequence polarity on DNA curvature.
AB  - Gel retardation studies and other experiments indicate that DNA sequences
      containing the d(GA4T4C)n motif are curved, whereas those of identical
      composition but with a reverse sequence polarity, the d(GT4A4C)n motif, are
      straight. Hydroxyl radical cleavage experiments show that d(GA4T4C)n shows a
      unique signature, whereas d(GT4A4C)n behaves normally. To explain these results
      at a molecular level, molecular dynamics (MD) simulations were performed on the
      DNA duplexes d(G5-(GA4T4C)2-C5) and d(G5-(GT4A4C)2-C5) to 3.0 and 2.5 ns,
      respectively. The MD simulations are based on the Cornell force field implemented
      in the AMBER 4.1 modeling package and performed in a neutral solution of anionic
      DNA with K+, Cl- and Mg2+ at concentrations roughly comparable to a ligase
      buffer. Long range interactions were treated by the particle mesh Ewald method.
      Analysis of the results shows that the calculated dynamical structure of d(G5
      (GA4T4C)2-C5) exhibits strong gross curvature, consistent with the observed
      behavior. The most significant locus of curvature in the MD structure is found at
      the central C15-G16 step, with an average roll angle of 12.8(+/-6.40)deg. The
      d(G5-(GT4A4C)2-C5) MD structure exhibited significantly less gross curvature.
      Analysis of results indicates that the reduction in gross curvature in the d(G5
      (GT4A4C)2-C5) trajectory originates from the effect of the T10-A11 and T20-A21
      steps, which showed average roll angles of 12.5(+/-5)deg. These three steps, T10
      A11, C15-G16 and T20-A21, are half-helix turns away from one another, and their
      contributions to concerted bending cancel out. The A-tracts in the MD structure
      are essentially straight. The dynamical structure of d(G5-(GA4T4C)2-C5) exhibited
      minor groove deformation comprised of expansion at the 5' end of A-tracts and
      progressive narrowing towards the 3' end, consistent with and elaborating the
      interpretation of hydroxyl radical chemical probing results.

PMID- 9917402
TI  - A detailed structural description of Escherichia coli succinyl-CoA synthetase.
AB  - Succinyl-CoA synthetase (SCS) carries out the substrate-level phosphorylation of
      GDP or ADP in the citric acid cycle. A molecular model of the enzyme from
      Escherichia coli, crystallized in the presence of CoA, has been refined against
      data collected to 2.3 A resolution. The crystals are of space group P4322, having
      unit cell dimensions a=b=98.68 A, c=403.76 A and the data set includes the data
      measured from 23 crystals. E. coli SCS is an (alphabeta)2-tetramer; there are two
      copies of each subunit in the asymmetric unit of the crystals. The crystal
      packing leaves two choices for which pair of alphabeta-dimers form the
      physiologically relevant tetramer. The copies of the alphabeta-dimer are similar,
      each having one active site where the phosphorylated histidine residue and the
      thiol group of CoA are found. CoA is bound in an extended conformation to the
      nucleotide-binding motif in the N-terminal domain of the alpha-subunit. The
      phosphoryl group of the phosphorylated histidine residue is positioned at the
      amino termini of two alpha-helices, one from the C-terminal domain of the alpha
      subunit and the other from the C-terminal domain of the beta-subunit. These two
      domains have similar topologies, despite only 14 % sequence identity. By analogy
      to other nucleotide-binding proteins, the binding site for the nucleotide may
      reside in the N-terminal domain of the beta-subunit. If this is so, the catalytic
      histidine residue would have to move about 35 A to react with the nucleotide.

PMID- 9917403
TI  - A dimeric form of Escherichia coli succinyl-CoA synthetase produced by site
      directed mutagenesis.
AB  - Succinyl-CoA synthetase (SCS) catalyzes the substrate-level phosphorylation step
      of the citric acid cycle. The enzyme from Escherichia coli is an (alphabeta)2
      heterotetramer with two active sites, one in each alphabeta-dimer. To determine
      whether the two active sites could function independently, mutations were made to
      split the tetramer into alphabeta-dimers. Because two choices for the tetramer (I
      and II) were possible from the X-ray crystallographic analyses, mutations were
      made at two different interfaces. All mutations based on tetramer I resulted in
      an intact tetramer. Of the two mutants based on tetramer II, one was insoluble
      and the other, where M156beta, Y158beta, R161beta and E162beta were changed to D,
      D, E and R, respectively, was a dimer. This quaternary structure was confirmed by
      fast protein liquid chromatography, blue native PAGE and ultracentrifugation. The
      DDER mutant has kinetic parameters similar to the tetrameric E. coli enzyme. Like
      the tetrameric enzyme, it shows ATP-facilitated dethiophosphorylation, proving
      that this property is a single-site effect. The ATP-facilitated
      dethiophosphorylation is inhibited by phosphate. It is concluded that
      dimerization of alphabeta-dimers is not a prerequisite for catalytic competency
      nor for alternating sites cooperativity in the tetramer. The rationale behind the
      dimer-of-dimers in E. coli SCS is still not known, but increased solubility,
      increased stability and in vivo interactions of the tetramer with other proteins
      are still possibilities.

PMID- 9917404
TI  - Crystal structure of CcdB, a topoisomerase poison from E. coli.
AB  - The crystal structure of CcdB, a protein that poisons Escherichia coli gyrase,
      was determined in three crystal forms. The protein consists of a five-stranded
      antiparallel beta-pleated sheet followed by a C-terminal alpha-helix. In one of
      the loops of the sheet, a second small three-stranded antiparallel beta-sheet is
      inserted that sticks out of the molecule as a wing. This wing contains the LysC
      proteolytic cleavage site that is protected by CcdA and, therefore, forms a
      likely CcdA recognition site. A dimer is formed by sheet extension and by
      extensive hydrophobic contacts involving three of the five methionine residues
      and the C terminus of the alpha-helix. The surface of the dimer on the side of
      the alpha-helix is overall negatively charged, while the opposite side as well as
      the wing sheet is dominated by positive charges. We propose that the CcdB dimer
      binds into the central hole of the 59 kDa N-terminal fragment of GyrA, after
      disruption of the head dimer interface of GyrA.

PMID- 9917405
TI  - Structure of the d(CGCCCGCGGGCG) dodecamer: a kinked A-DNA molecule showing some
      B-DNA features.
AB  - We have determined the structure of the dodecamer duplex d(CGCCCGCGGGCG)2. A
      careful use of the molecular replacement programme AMoRe has been essential in
      order to solve the structure. This dodecamer shows a unique conformation, quite
      different from all the previously studied oligonucleotide duplexes: the central
      octamer has an A conformation, but with a sharp 65 degrees kink in the centre;
      the terminal base-steps have a B-like conformation; the major groove is
      completely closed in the centre, a hollow molecule is thus found. The results
      obtained confirm the high degree of variability of DNA structure. A new type of
      kink and an intermediate A/B double-helical conformation have been found. Such
      intermediate conformation differs from those described in DNA polymerase
      complexes.

PMID- 9917406
TI  - A branch and bound algorithm for protein structure refinement from sparse NMR
      data sets.
AB  - We describe new methods for predicting protein tertiary structures to low
      resolution given the specification of secondary structure and a limited set of
      long-range NMR distance constraints. The NMR data sets are derived from a
      realistic protocol involving completely deuterated 15N and 13C-labeled samples. A
      global optimization method, based upon a modification of the alphaBB (branch and
      bound) algorithm of Floudas and co-workers, is employed to minimize an objective
      function combining the NMR distance restraints with a residue-based protein
      folding potential containing hydrophobicity, excluded volume, and van der Waals
      interactions. To assess the efficacy of the new methodology, results are compared
      with benchmark calculations performed via the X-PLOR program of Brunger and co
      workers using standard distance geometry/molecular dynamics (DGMD) calculations.
      Seven mixed alpha/beta proteins are examined, up to a size of 183 residues, which
      our methods are able to treat with a relatively modest computational effort,
      considering the size of the conformational space. In all cases, our new approach
      provides substantial improvement in root-mean-square deviation from the native
      structure over the DGMD results; in many cases, the DGMD results are
      qualitatively in error, whereas the new method uniformly produces high quality
      low-resolution structures. The DGMD structures, for example, are systematically
      non-compact, which probably results from the lack of a hydrophobic term in the X
      PLOR energy function. These results are highly encouraging as to the possibility
      of developing computational/NMR protocols for accelerating structure
      determination in larger proteins, where data sets are often underconstrained.

PMID- 9917407
TI  - Visualizing and quantifying molecular goodness-of-fit: small-probe contact dots
      with explicit hydrogen atoms.
AB  - The technique of small-probe contact dot surfaces is described as a method for
      calculating and displaying the detailed atomic contacts inside or between
      molecules. It allows one both to measure and to visualize directly the goodness
      of-fit of packing interactions. It requires both highly accurate structures and
      also the explicit inclusion of all hydrogen atoms and their van der Waals
      interactions. A reference dataset of 100 protein structures was chosen on the
      basis of resolution (1.7 A or better), crystallographic R-value, non-homology,
      and the absence of any unusual problems. Hydrogen atoms were added in standard
      geometry and, where needed, with rotational optimization of OH, SH, and NH+3
      positions. Side-chain amide orientations were corrected where required by NH van
      der Waals clashes, as described in the accompanying paper. It was determined
      that, in general, methyl groups pack well in the default staggered conformation,
      except for the terminal methyl groups of methionine residues, which required
      rotational optimization. The distribution of serious clashes (i.e. non-H-bond
      overlap of >/=0.4 A) was studied as a function of resolution, alternate
      conformations, and temperature factor (B), leading to the decision that packing
      and other structural features would not be analyzed for residues in 'b' alternate
      conformations or with B-factors of 40 or above. At the level of the fine details
      analyzed here, structural accuracy improves quite significantly over the range
      from 1.7 to 1.0 A resolution. These high-resolution structures show impressively
      well-fitted packing interactions, with some regions thoroughly interdigitated and
      other regions somewhat sparser. Lower-resolution structures or model structures
      could undoubtedly be improved in accuracy by the incorporation of this additional
      information: for example, nucleic acid structures in non-canonical conformations
      are often very accurate for the bases and much less reliable for the backbone,
      whose conformation could be specified better by including explicit H atom
      geometry and contacts. The contact dots are an extremely sensitive method of
      finding problem areas, and often they can suggest how to make improvements. They
      can also provide explanations for structural features that have been described
      only as empirical regularities, which is illustrated by showing that the
      commonest rotamer of methionine (a left-handed spiral, with all chi values near 
      60 degrees) is preferred because it provides up to five good H atom van der Waals
      contacts. This methodology is thus applicable in two different ways: (1) for
      finding and correcting errors in structure models (either experimental or
      theoretical); and (2) for analyzing interaction patterns in the molecules
      themselves.

PMID- 9917408
TI  - Asparagine and glutamine: using hydrogen atom contacts in the choice of side
      chain amide orientation.
AB  - Small-probe contact dot surface analysis, with all explicit hydrogen atoms added
      and their van der Waals contacts included, was used to choose between the two
      possible orientations for each of 1554 asparagine (Asn) and glutamine (Gln) side
      chain amide groups in a dataset of 100 unrelated, high-quality protein crystal
      structures at 0.9 to 1.7 A resolution. For the movable-H groups, each connected,
      closed set of local H-bonds was optimized for both H-bonds and van der Waals
      overlaps. In addition to the Asn/Gln "flips", this process included rotation of
      OH, SH, NH3+, and methionine methyl H atoms, flip and protonation state of
      histidine rings, interaction with bound ligands, and a simple model of water
      interactions. However, except for switching N and O identity for amide flips (or
      N and C identity for His flips), no non-H atoms were shifted. Even in these very
      high-quality structures, about 20 % of the Asn/Gln side-chains required a 180
      degrees flip to optimize H-bonding and/or to avoid NH2 clashes with neighboring
      atoms (incorporating a conservative score penalty which, for marginal cases,
      favors the assignment in the original coordinate file). The programs Reduce,
      Probe, and Mage provide not only a suggested amide orientation, but also a
      numerical score comparison, a categorization of the marginal cases, and a direct
      visualization of all relevant interactions in both orientations. Visual
      examination allowed confirmation of the raw score assignment for about 40 % of
      those Asn/Gln flips placed within the "marginal" penalty range by the automated
      algorithm, while uncovering only a small number of cases whose automated
      assignment was incorrect because of special circumstances not yet handled by the
      algorithm. It seems that the H-bond and the atomic-clash criteria independently
      look at the same structural realities: when both criteria gave a clear answer
      they agreed every time. But consideration of van der Waals clashes settled many
      additional cases for which H-bonding was either absent or approximately
      equivalent for the two main alternatives. With this extra information, 86 % of
      all side-chain amide groups could be oriented quite unambiguously. In the absence
      of further experimental data, it would probably be inappropriate to assign many
      more than this. Some of the remaining 14 % are ambiguous because of coordinate
      error or inadequacy of the theoretical model, but the great majority of ambiguous
      cases probably occur as a dynamic mix of both flip states in the actual protein
      molecule. The software and the 100 coordinate files with all H atoms added and
      optimized and with amide flips corrected are publicly available.

PMID- 9917409
TI  - NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus
      quinquestriatus hebraeus.
AB  - NMR structures of a new toxin from the scorpion Leiurus quinquestriatus hebraeus
      (Lqh III) have been investigated in conjunction with its pharmacological
      properties. This toxin is proposed to belong to a new group of scorpion toxins,
      the alpha-like toxins that target voltage-gated sodium channels with specific
      properties compared with the classical alpha-scorpion toxins.
      Electrophysiological analysis showed that Lqh III inhibits a sodium current
      inactivation in the cockroach axon, but induces in addition a resting
      depolarization due to a slowly decaying tail current atypical to other alpha
      toxin action. Binding studies indicated that radiolabeled Lqh III binds with a
      high degree of affinity (Ki=2.2 nM) on cockroach sodium channels and that the
      alpha-toxin from L quinquestriatus hebraeus highly active on insects (LqhalphaIT)
      and alpha-like toxins compete at low concentration for its receptor binding site,
      suggesting that the alpha-like toxin receptor site is partially overlapping with
      the receptor site 3. Conversely, in rat brain, Lqh III competes for binding of
      the most potent anti-mammal alpha-toxin from Androctonus australis Hector venom
      (AaH II) only at very high concentration. The NMR structures were used for the
      scrutiny of the similarities and differences with representative scorpion alpha
      toxins targeting the voltage-gated sodium channels of either mammals or insects.
      Three turn regions involved in the functional binding site of the anti-insect
      LqhalphaIT toxin reveal significant differences in the Lqh III structure. The
      electrostatic charge distribution in the Lqh III toxin is also surprisingly
      different when compared with the anti-mammal alpha-toxin AaH II. Similarities in
      the electrostatic charge distribution are, however, recognized between alpha
      toxins highly active on insects and the alpha-like toxin Lqh III. This affords
      additional important elements to the definition of the new alpha-like group of
      scorpion toxins and the mammal versus insect scorpion toxin selectivities.

PMID- 9917410
TI  - Native Escherichia coli and murine dihydrofolate reductases contain late-folding
      non-native structures.
AB  - We have examined the equilibrium and kinetic folding properties of two
      structurally homologous dihydrofolate reductases, Escherichia coli DHFR (EcDHFR)
      and murine DHFR (MuDHFR), as a function of temperature and ligand concentration.
      Conformational heterogeneity in native DHFR is well documented, and the results
      demonstrate that the non-native form(s) represents late intermediate(s) in the
      folding process. We have measured the concentrations of native and non-native
      forms and the rate constants for their interconversion over a temperature range
      of 3 degreesC to 49 degreesC, allowing characterization of the thermodynamic as
      well as the kinetic properties of the final folding step(s) relative to the
      overall folding reaction. Differences in ligand binding suggest that the
      intermediate structures for these two proteins may be different during refolding.

PMID- 9917411
TI  - The chaperonin GroEL binds to late-folding non-native conformations present in
      native Escherichia coli and murine dihydrofolate reductases.
AB  - Dihydrofolate reductases from mouse (MuDHFR) or Escherichia coli (EcDHFR) are
      shown to refold via several intermediate forms, each of which can bind to the
      chaperonin GroEL. When stable complexes with GroEL are formed, they consist of
      late-folding intermediates. In addition, we find that late-folding intermediates
      that are present in the native enzyme bind to GroEL. For the E. coli and murine
      proteins, the extent of protein bound increases as the temperature is increased
      from 8 degreesC to 42 degreesC, at which temperature either protein is completely
      bound as the last (EcDHFR) or the last two (MuDHFR) folding intermediate(s). Thus
      for EcDHFR, the binding is transient at low temperature (<30 degreesC) and stable
      at high temperature (>35 degreesC). For MuDHFR, complex formation appears less
      temperature dependent. In general, the data demonstrate that the overall binding
      free energy for the interaction of GroEL with native DHFR is the sum of the free
      energy for the first step in DHFR unfolding, which is unfavorable, and the free
      energy of binding the non-native conformation, which is favorable. For EcDHFR,
      this results in an overall binding free energy that is unfavorable below 30
      degreesC. Over the temperature range of 8 degreesC to 42 degreesC, GroEL binds
      MuDHFR more tightly than EcDHFR, due partially to a small free energy difference
      between two pre-existing non-native conformations of MuDHFR, resulting in binding
      to more than one folding intermediate.

PMID- 9917412
TI  - The bacterial SecY/E translocation complex forms channel-like structures similar
      to those of the eukaryotic Sec61p complex.
AB  - The SecYEG complex is a major component of the protein translocation apparatus in
      the cytoplasmic membrane of bacteria. We have purified a translocationally active
      complex of the two subunits, SecY and SecE, from Bacillus subtilis. As
      demonstrated by electron microscopy, SecY/E forms ring structures in detergent
      solution and in intact lipid bilayers, often with a quasi-pentagonal appearance
      in projection. The particles represent oligomeric assemblies of the SecY/E
      complex and are similar to those formed by the eukaryotic Sec61p complex. We
      propose that these SecY/E rings represent protein-conducting channels and that
      the two essential membrane components SecY and SecE are sufficient for their
      formation.

PMID- 9917413
TI  - Membrane assembly of the Escherichia coli outer membrane protein OmpA: exploring
      sequence constraints on transmembrane beta-strands.
AB  - The eight-stranded antiparallel beta-barrel domain of the OmpA protein from
      Escherichia coli serves as a paradigm for the study of membrane assembly of
      integral beta-structured membrane proteins. Previous studies have shown that
      neither the periplasmic turns nor the surface-exposed loops contain topogenic
      information. Consequently, the question of whether any structural constraint is
      imposed onto individual transmembrane beta-strands is now addressed. To this end,
      amino acid sequences of beta-strands 4, 6 and 8 were randomized. In vivo membrane
      assembly of mutant proteins was assayed and 288 variants were sequenced. Three
      parameters were found to be important for efficient membrane assembly. (i) At
      least four of five randomized residues with side-chains pointing towards the
      lipid bilayer must be hydrophobic and none of the three central residues must be
      charged. (ii) Side-chains pointing into the beta-barrel interior must not be
      enlarged too much, possibly because of packing constraints. (iii) Proline
      residues are, in general, hardly tolerated in the transmembrane beta-strands.

PMID- 9917414
TI  - Molecular dynamics simulations of the hyperthermophilic protein sac7d from
      Sulfolobus acidocaldarius: contribution of salt bridges to thermostability.
AB  - Hyperthermophilic proteins often possess an increased number of surface salt
      bridges compared with their mesophilic homologues. However, salt bridges are
      generally thought to be of minor importance in protein stability at room
      temperature. In an effort to understand why this may no longer be true at
      elevated temperatures, we performed molecular dynamics simulations of the
      hyperthermophilic protein Sac7d at 300 K, 360 K, and 550 K. The three
      trajectories are stable on the nanosecond timescale, as evidenced by the analysis
      of several time-resolved properties. The simulations at 300 K and (to a lesser
      extent) 360 K are also compatible with nuclear Overhauser effect-derived
      distances. Raising the temperature from 300 K to 360 K results in a less
      favourable protein-solvent interaction energy, and a more favourable intraprotein
      interaction energy. Both effects are almost exclusively electrostatic in nature
      and dominated by contributions due to charged side-chains. The reduced solvation
      is due to a loss of spatial and orientational structure of water around charged
      side-chains, which is a consequence of the increased thermal motion in the
      solvent. The favourable change in the intraprotein Coulombic interaction energy
      is essentially due to the tightening of salt bridges. Assuming that charged side
      chains are on average more distant from one another in the unfolded state than in
      the folded state, it follows that salt bridges may contribute to protein
      stability at elevated temperatures because (i) the solvation free energy of
      charged side-chains is more adversely affected in the unfolded state than in the
      folded state by an increase in temperature, and (ii) due to the tightening of
      salt bridges, unfolding implies a larger unfavourable increase in the
      intraprotein Coulombic energy at higher temperature. Possible causes for the
      unexpected stability of the protein at 550 K are also discussed.

PMID- 9917415
TI  - Folding, heterodimeric association and specific peptide recognition of a murine
      alphabeta T-cell receptor expressed in Escherichia coli.
AB  - In a systematic study of the murine T-cell receptor UZ3-4, expressed and refolded
      from inclusion bodies in Escherichia coli, it was found that functional molecules
      can be obtained only under a very narrow set of conditions. The refolded T-cell
      receptor UZ3-4 specifically recognizes its cognate peptide (from mycobacterial
      Hsp60) in the context of H-2Db, but not another peptide bound to H-2Db, and the
      dissociation constant was determined by BIAcore as 10(-4) M. Using T-cell
      receptor constructs comprising all extracellular domains (ValphaCalpha and
      VbetaCbeta), found to be necessary for stability of the final product,
      significant amounts of native molecules were obtained only if the intermolecular
      Calpha-Cbeta disulfide bridge bond was deleted, even though the interaction
      between the complete alpha and beta-chain was determined to be very weak and
      fully reversible (KD approximately 10(-7) to 10(-6) M). Fusion of Jun and Fos to
      the constant domains also decreased the folding yield, because of premature
      association of intermediates leading to aggregation. Furthermore, only in a very
      narrow set of concentrations of oxidized and reduced glutathione, native
      disulfide bonds dominated. This shows that T-cell receptor domains are very prone
      to aggregation and misassociation during folding, compounded by incorrect
      disulfide bond formation. Once folded, however, the heterodimeric molecule is
      very stable and could be concentrated to millimolar concentration.

PMID- 9917416
TI  - Structure of the insect troponin complex.
AB  - Isolated troponin-tropomyosin complex from Lethocerus indicus asynchronous flight
      muscle forms paracrystals on a positively charged lipid monolayer. Single
      particle analysis was carried out on individual complexes selected from electron
      micrographs of negatively stained paracrystals. By a combination of correlation
      and classification techniques, different average projections of the object were
      obtained. An initial three-dimensional model was calculated by determining the
      Euler angles for the different views using a common line approach. This starting
      model was then used as a reference for the further three-dimensional refinement
      of the model using the original data set. The refined model of the troponin
      complex has a diameter of approximately 90 A and a volume corresponding with a
      molecular mass of about 120 kDa for the globular domain. The resolution of the
      reconstruction was determined to be 32 A using the differential phase residual
      method and 26 A using the Fourier shell correlation criterion.

PMID- 9917417
TI  - Engineered assembly of intertwined oligomers of an immunoglobulin chain.
AB  - Domain 1 of CD2 (CD2.D1) forms a conventional Ig fold stabilised by non-covalent
      antiparallel contacts between beta-strands. Removing two residues from the middle
      of the protein sequence, where the polypeptide chain normally folds back upon
      itself, stabilises an open conformation. In this modified molecule, the optimum
      evolved contacts between side-chains can only be satisfied through the
      antiparallel association of two chains to create a symmetrical pair of pseudo
      domains. Here, we describe the dynamics of the switch between monomeric and
      dimeric states and demonstrate the extension of this novel underlying principle
      to trimer and tetramer formation. The ability of a protein molecule to form
      higher-order antiparallel structures is reminiscent of the behaviour of hairpins,
      duplexes, three-way and Holliday junctions in DNA.

PMID- 9917418
TI  - Stability and folding of the tumour suppressor protein p16.
AB  - The tumour suppressor p16 is a member of the INK4 family of inhibi tors of the
      cyclin D-dependent kinases, CDK4 and CDK6, that are involved in the key growth
      control pathway of the eukaryotic cell cycle. The 156 amino acid residue protein
      is composed of four ankyrin repeats (a helix-turn-helix motif) that stack
      linearly as two four-helix bundles resulting in a non-globular, elongated
      molecule. The thermodynamic and kinetic properties of the folding of p16 are
      unusual. The protein has a very low free energy of unfolding, Delta GH-2O/D-N, of
      3.1 kcal mol-1 at 25 degreesC. The rate-determining transition state of
      folding/unfolding is very compact (89% as compact as the native state). The other
      unusual feature is the very rapid rate of unfolding in the absence of denaturant
      of 0.8 s-1 at 25 degreesC. Thus, p16 has both thermodynamic and kinetic
      instability. These features may be essential for the regulatory function of the
      INK4 proteins and of other ankyrin-repeat-containing proteins that mediate a wide
      range of protein-protein interactions. The mechanisms of inactivation of p16 by
      eight cancer-associated mutations were dissected using a systematic method
      designed to probe the integrity of the secondary structure and the global fold.
      The structure and folding of p16 appear to be highly vulnerable to single point
      mutations, probably as a result of the protein's low stability. This
      vulnerability provides one explanation for the striking frequency of p16
      mutations in tumours and in immortalised cell lines.

PMID- 9917419
TI  - Recognition of spatial motifs in protein structures.
AB  - As the structural database continues to expand, new methods are required to
      analyse and compare protein structures. Whereas the recognition, comparison, and
      classification of folds is now more or less a solved problem, tools for the study
      of constellations of small numbers of residues are few and far between. In this
      paper, two programs are described for the analysis of spatial motifs in protein
      structures. The first, SPASM, can be used to find the occurrence of a motif
      consisting of arbitrary main-chain and/or side-chains in a database of protein
      structures. The program also has a unique capability to carry out "fuzzy pattern
      matching" with relaxed requirements on the types of some or all of the matching
      residues. The second program, RIGOR, scans a single protein structure for the
      occurrence of any of a set of pre-defined motifs from a database. In one
      application, spatial motif recognition combined with profile analysis enabled the
      assignment of the structural and functional class of an uncharacterised
      hypothetical protein in the sequence database. In another application, the
      occurrence of short left-handed helical segments in protein structures was
      investigated, and such segments were found to be fairly common. Potential
      applications of the techniques presented here lie in the analysis of (newly
      determined) structures, in comparative structural analysis, in the design and
      engineering of novel functional sites, and in the prediction of structure and
      function of uncharacterised proteins.

PMID- 9917421
TI  - Effects of an amphipathic drug on the rheological properties of the cell
      membrane.
AB  - Sodium thiopental, as other amphiphilic molecules, interacts with the membrane by
      inserting into the lipid bilayer and causing alterations of the membrane
      properties such as curvature and hypotonic lysis resistance. But can it modify
      the mechanical properties of the membrane? In the present work it was observed
      that sodium thiopental affected the membrane rheological properties by improving
      erythrocyte deformability; this effect resulted from a reduction of both the
      elastic modulus and surface viscosity. In erythrocytes devoid of sialic acid
      after treatment with neuraminidase, sodium thiopental membrane concentration was
      significantly higher than in normal cells, suggesting that drug access to the
      lipid bilayer be facilitated by the absence of the steric and electrostatic
      barrier of the glycocalyx negative charges. From a rheological point of view,
      desialated and normal cells showed the same response to the anesthetic as regards
      elastic modulus but in opposite direction if surface viscosity was considered.
      This finding supports the hypothesis that sodium thiopental molecules enter the
      bilayer of desialated cells in a higher proportion, as compared to the normal
      erythrocyte, promoting a disorganization that results in a greater inner
      friction. The changes in the rheological parameters, triggered by sodium
      thiopental, could be attributed to the bilayer contribution to the membrane
      mechanical properties, either directly or through interaction between the bilayer
      and the cytoskeleton.

PMID- 9917422
TI  - The Hexagon Condition and Additive Representation for Two Dimensions: An
      Algebraic Approach.
AB  - Within the algebraic approach the Thomsen condition may be replaced with the
      hexagon condition to imply the existence of additive representation for two
      dimensions. In some models the Thomsen condition does not have a natural
      interpretation whereas the hexagon condition does, which makes it better suited
      for axiomatic theories. Copyright 1998 Academic Press.

PMID- 9917423
TI  - A General Formulation for Unidimensional Unfolding and Pairwise Preference
      Models: Making Explicit the Latitude of Acceptance.
AB  - Probabilistic unfolding models for direct responses of persons to statements are
      characterised by single peaked response functions. The range in which a positive
      response is most likely is termed the latitude of acceptance, a well known but
      little researched concept in the modelling of attitude measurement. This paper
      derives a general form for probabilistic unfolding models in which a natural
      parameter characterises the latitude of acceptance. It is shown that a number of
      already known models for unfolding can be reexpressed in this general form with
      different operational functions and that, in doing so, the implied latitude of
      acceptance for these models is identified. It is also shown that other unfolding
      models can be generated readily by specifying the operational function of the
      general form. A general form for pairwise preference models is also presented. A
      discussion on the latitude of acceptance parameter as a scale parameter is also
      provided. Copyright 1998 Academic Press.

PMID- 9917424
TI  - A Qualitative Characterization of the Exponential Distribution.
AB  - An axiomization of a random variable representation is developed. The existence
      of the probability measure with respect to which the representations are
      measurable is derived from qualitative conditions in the sense of measurement
      theory. The structure is based on a combination of a difference with an extensive
      measurement structure. Furthermore, a special condition, qualitative as the
      others, is shown to yield the result that the real valued representations of the
      structure are random variables with an exponential distribution. The key property
      is a condition relating the difference order and the concatenation in such a way
      that shifting two intervals by concatenating their endpoints with the same
      element does not affect their order relation. Copyright 1998 Academic Press.

PMID- 9917425
TI  - A New Method for Estimating Model Parameters for Multinomial Data.
AB  - A new procedure for estimating the parameters of a scientific model is described,
      and the method is applied and illustrated for the class of experiments with
      multinominal data structure. The procedure is referred to as the method of
      population-parameter mapping, and it has a number of novel and advantageous
      features. The method is a variation of a standard Bayesian analysis. However,
      instead of directly developing a posterior distribution for the model parameters,
      this procedure first characterizes the population proportions for the multinomial
      cells. Random samples are then drawn from the posterior distribution for these
      proportions, and these samples are mapped to the parameters of the scientific
      model. This method leads naturally to a definition of model identifiability, and
      leads to a direct probability estimate of the coherence of the scientific model.
      Moreover, the new procedure can circumvent the problem of dealing with
      computationally difficult integrals that frequently occur with Bayesian analyses
      of complex multinomial models. The method is illustrated by means of several
      memory measurement models as well as a signal-detection model. Copyright 1998
      Academic Press.

PMID- 9917426
TI  - 30th Annual Meeting of the Society for Mathematical Psychology.

PMID- 9917427
TI  - 29th EMPG Meeting.

PMID- 9917429
TI  - TELEGRAPHIC REVIEWS.

PMID- 9917430
TI  - RECENTLY ACCEPTED MANUSCRIPTS.

PMID- 9917431
TI  - Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of
      bilirubin production Sn-mesoporphyrin.
AB  - OBJECTIVE: To assess the efficacy of Sn-mesoporphyrin (SnMP), a potent inhibitor
      of bilirubin production, in: a) moderating the need for phototherapy (PT) in full
      term breastfed infants with plasma bilirubin concentrations (PBC) of >/=256.5
      micromol/L and </=307.8 micromol/L (>/=15 mg/dL and </=18 mg/dL, respectively)
      that were reached between >/=48 and </=96 hours of age; b) diminishing the time
      required for the PBC to decline to </=222.3 micromol/L (</=13 mg/dL) (closure of
      the case); c) decreasing the number of bilirubin determinations required for
      monitoring hyperbilirubinemia. STUDY PARTICIPANTS: Healthy full-term breastfed
      infants with a PBC between >/=256.5 micromol/L and </=307.8 micromol/L (>/=15
      mg/dL and </=18 mg/dL, respectively) reached between 48 to 96 hours of age.
      DESIGN/METHODS: After obtaining informed consent from the parents, infants were
      randomized to either the SnMP (6.0 micromol/kg birth weight, single dose,
      intramuscular) group or the control group. The infants' PBCs were followed by
      daily measurements either in the hospital or at discharge as outpatients until
      the hyperbilirubinemia had subsided (PBC </=222.3 micromol/L [13mg/dL]). The
      total number of newborns enrolled in the study was 84; the SnMP group comprised
      40 infants; the control group comprised 44 infants. The groups were similar in
      sex ratio, birth weight, gestational age, PBC, and age at enrollment. All infants
      were breastfed. Phototherapy was initiated at a PBC of 333.5 micromol/dL (19.5
      mg/dL). RESULTS: SnMP entirely eliminated the need for supplemental PT to control
      hyperbilirubinemia; in contrast, of the 44 control infants, 12 required treatment
      with PT (27%) when their PBC reached or exceeded the level (333.5 micromol/dL;
      19.5 mg/dL) at which time the use of PT was dictated by hospital guidelines. None
      of the 40 SnMP-treated infants reached a PBC of 19.5 mg/dL. SnMP also markedly
      diminished the median hours to case closure (SnMP: median, 86.5 hours;
      minimum/maximum, 24/216 hours; controls: median, 120 hours; minimum/maximum,
      72/336 hours); and significantly reduced the number of bilirubin determinations
      required for clinical monitoring of the infants (SnMP: median, 3;
      minimum/maximum, 1/9; controls: median, 5; minimum/maximum, 3/11). No adverse
      effects of SnMP use were observed. CONCLUSION: A single dose of SnMP proved
      effective in controlling severe hyperbilirubinemia in full-term breastfed
      newborns with high bilirubin levels between 48 and 96 hours. In addition, SnMP
      eliminated the need for PT and reduced the use of medical resources in the
      clinical treatment of this problem as well as the related, important and painful,
      emotional costs for both mothers and infants.

PMID- 9917432
TI  - Predictive ability of a predischarge hour-specific serum bilirubin for subsequent
      significant hyperbilirubinemia in healthy term and near-term newborns.
AB  - OBJECTIVE: To assess the predictive ability of a universal predischarge serum
      bilirubin measurement to screen for risk of subsequent significant
      hyperbilirubinemia in the direct Coombs negative healthy term and near-term
      newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB)
      levels were obtained at the time of the routine metabolic screen in all term and
      near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n =
      13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A
      percentile-based bilirubin nomogram for the first week was constructed from hour
      specific predischarge and postdischarge TSB values of newborns (n = 2840; median
      BW = 3230 g and median gestational age = 39 weeks) who met classification
      criteria for healthy newborns (excluding those with a positive direct Coombs test
      or those requiring phototherapy before age 60 hours) and who were enrolled in a
      hospital supervised home or outpatient follow-up program. The accuracy of the
      predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was
      determined. RESULTS: The study patients in the nomogram were racially diverse.
      Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840)
      had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of
      these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08,
      sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1%
      of the population (912/2840) had TSB values in the intermediate-risk zone. In a
      clinically significant minority of these newborns (58/912 or 6.4%), the
      postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the
      upper-intermediate zone and.48 from the lower-intermediate risk zone). The
      predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone
      (<40th percentile) and there was no measurable risk for significant
      hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability
      = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict
      which newborn is at high, intermediate or low risk for developing clinically
      significant hyperbilirubinemia (specifically defined as TSB levels >/=95th
      percentile for age in hours). Risk designation and subsequent increases or
      decreases of in TSB can be easily monitored on an hour-specific percentile based
      predictive bilirubin nomogram. A predischarge TSB measured as a universal policy
      would facilitate targeted intervention and follow-up in a safe, cost-effective
      manner. In conjunction with bilirubin practice parameter of the American Academy
      of Pediatrics, it could reduce the potential risk for bilirubin-induced
      neurologic dysfunction.

PMID- 9917433
TI  - A longitudinal study of otitis media with effusion among 2- to 5-year-old African
      American children in child care.
AB  - OBJECTIVE: To prospectively document the prevalence of otitis media with effusion
      (OME) in 86 African-American children between ages 2 and 5 years. STUDY DESIGN:
      Eighty-six children in center-based child care whose ear status had been followed
      from infancy continued to be observed. Middle ear status was assessed by
      pneumatic otoscopy and tympanometry biweekly. RESULTS: The prevalence of OME
      decreased as children became older. The mean proportion of examinations
      demonstrating bilateral OME (BOME) ranged from 12% between 24 to 30 months to 4%
      between 54 to 60 months of age. The mean proportion of exams revealing bilateral
      normal ears increased from 77% at 24 to 30 months to 88% at 54 to 60 months of
      age. Although 60 children had experienced BOME that lasted 4 months or longer in
      the 6- to 24-month age period, only 8 of these children experienced at least 4
      months of continuous BOME between 24 to 60 months. CONCLUSIONS: The proportion of
      time with BOME decreased progressively with increasing age in this population.
      Only 8 of 60 children who had experienced more than 4 consecutive months of BOME
      before 2 years of age continued to manifest persistent effusion or experience
      recurrences of prolonged BOME after 2 years of age.

PMID- 9917434
TI  - Effect of a pediatric trauma response team on emergency department treatment time
      and mortality of pediatric trauma victims.
AB  - OBJECTIVE: Delay in the provision of definitive care for critically injured
      children may adversely effect outcome. We sought to speed care in the emergency
      department (ED) for trauma victims by organizing a formal trauma response system.
      DESIGN: A case-control study of severely injured children, comparing those who
      received treatment before and after the creation of a formal trauma response
      team. SETTING: A tertiary pediatric referral hospital that is a locally
      designated pediatric trauma center, and also receives trauma victims from a
      geographically large area of the Western United States. SUBJECTS: Pediatric
      trauma victims identified as critically injured (designated as "trauma one") and
      treated by a hospital trauma response team during the first year of its
      existence. Control patients were matched with subjects by probability of survival
      scores, and were chosen from pediatric trauma victims treated at the same
      hospital during the year preceding the creation of the trauma team.
      INTERVENTIONS: A trauma response team was organized to respond to pediatric
      trauma victims seen in the ED. The decision to activate the trauma team
      (designation of patient as "trauma one") is made by the pediatric emergency
      medicine (PEM) physician before patient arrival in the ED, based on data received
      from prehospital care providers. Activation results in the notification and
      immediate travel to the ED of a pediatric surgeon, neurosurgeon, emergency
      physician, intensivist, pharmacist, radiology technician, phlebotomist, and
      intensive care unit nurse, and mobilization of an operating room team. Most
      trauma one patients arrived by helicopter directly from accident scenes. OUTCOME
      MEASURES: Data recorded included identifying information, diagnosis, time to head
      computerized tomography, time required for ED treatment, admission Revised Trauma
      Score, discharge Injury Severity Score, surgical procedures performed, and
      mortality outcome. Trauma Injury Severity Score methodology was used to calculate
      the probability of survival and mortality compared with the reference patients of
      the Major Trauma Outcome Study, by calculation of z score. RESULTS: Patients
      treated in the ED after trauma team initiation had statistically shorter times
      from arrival to computerized tomography scanning (27 +/- 2 vs 21 +/- 4 minutes),
      operating room (63 +/- 16 vs 623 +/- 27 minutes) and total time in the ED (85 +/-
      8 vs 821 +/- 9 minutes). Calculation of z score showed that survival for the
      control group was not different from the reference population (z = -0.8068),
      although survival for trauma-one patients was significantly better than the
      reference population (z = 2.102). CONCLUSION: Before creation of the trauma team,
      relevant specialists were individually called to the ED for patient evaluation.
      When a formal trauma response team was organized, time required for ED treatment
      of severe trauma was decreased, and survival was better than predicted compared
      with the reference Major Trauma Outcome Study population.

PMID- 9917435
TI  - An evaluation of the safety and immunogenicity of a five-component acellular
      pertussis, diphtheria, and tetanus toxoid vaccine (DTaP) when combined with a
      Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (PRP-T) in
      Taiwanese infants.
AB  - OBJECTIVE: Immunologic interference particular to the Haemophilus influenzae type
      b (Hib) response has been observed with previous acellular pertussis-Hib
      combination vaccines. To test this hypothesis a clinical trial to assess the
      safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous
      hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis
      vaccine combined with diphtheria and tetanus toxoids (DTaP) when given
      simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in
      infants at 2, 4, 6, and 18 months of age was conducted. The study compared two
      methods of administration: both vaccines combined in a single syringe and
      administered as a single injection, or both vaccines administered concurrently
      but at separate sites of injection. METHODS: Healthy 2-month-old infants were
      enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral
      poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction
      information was collected by telephone 2 days after each vaccination. Serum was
      collected at 2, 6, 7, 18, and 19 months of age. RESULTS: One hundred thirty-five
      healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18
      month booster: 68 received the combined vaccine and 67 the separate vaccines. All
      vaccines were well tolerated. No differences in rates of local and systemic
      reactions were seen between the two methods of administration. No serious adverse
      events were reported. Serologic responses were comparable between the groups.
      Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7
      months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN
      (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for
      combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197),
      and FIM (892 vs 732). Only the 7-month PT response in the combined group was
      significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third
      dose (age 6 months), all subjects achieved serologic serum antibody levels
      indicative of protection against Hib, diphtheria, tetanus, and poliovirus types
      1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of
      protection (>/=0.15 microgram/mL) against Hib after only two doses. At 7 months,
      anti-PRP geometric mean titer values were 11.8 micrograms/mL in the combined
      group compared with 13.0 micrograms/mL in the separate group. The anti-PRP
      geometric mean titers after the 18-month booster were 58.5 micrograms/mL in the
      combined group versus 55.3 micrograms/mL in the separate group. CONCLUSION: The
      five-component DTaP vaccine may be combined with PRP-T vaccine without clinically
      significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month
      schedule.

PMID- 9917436
TI  - A randomized study of tracking with outreach and provider prompting to improve
      immunization coverage and primary care.
AB  - OBJECTIVE: To compare and measure the effects and cost-effectiveness of two
      interventions designed to raise immunization rates. SETTINGS: Nine primary care
      sites serving impoverished and middle-class children. SUBJECTS: Complete birth
      cohorts (ages 0 to 12 months; n = 3015) from these sites. INTERVENTIONS: Two 18
      month duration interventions: 1) tracking with outreach [tracking/outreach] to
      bring underimmunized children to their primary care provider office, and 2) a
      primary care provider office policy change to identify and reduce missed
      immunization opportunities (prompting). DESIGN: Randomized, controlled trial,
      randomizing within sites using a two-by-two factorial design. Subjects were
      allocated to one of four study groups: control, prompting only, tracking/outreach
      only, and combined prompting with tracking/outreach. Outcomes were obtained by
      blinded chart abstraction. MEASURES: Immunization status for age; number of days
      of delay in immunization; primary care utilization; and rates of screening for
      occult disease. RESULTS: Out of 3015 subjects, 274 subjects (9%) transferred out
      of the participating sites or had incomplete charts and were excluded. The 2741
      (91%) remaining subjects were assessed. At baseline, study groups did not differ
      in age, gender, insurance type, or immunization status. Of the remaining
      subjects, 63% received Medicaid. Final series-complete immunization coverage
      levels were: control, 74%; prompting-only, 76%; tracking/outreach-only 95%; and
      combined tracking/outreach with prompting, 95%. Analysis of variance showed that:
      1) tracking/outreach increased immunization rates 20 percentage points; 2)
      tracking/outreach decreased mean immunization delay 63 days; 3) tracking/outreach
      increased mean health supervision visits 0.44 visits per child; 4)
      tracking/outreach increased mean anemia screening 0.17 screenings per child and
      mean lead screenings 0.12 screenings per child; 5) impact of tracking/outreach
      was greatest for uninsured and impoverished patients; and 6) the prompting
      intervention had no impact on the studied outcomes, and its failure was caused by
      inconsistent use of prompts and failure to vaccinate ill children when prompted.
      Using tracking/outreach, the cost per additional child fully immunized was $474.
      Each $1000 spent on the tracking/outreach intervention resulted in: 2.1
      additional fully vaccinated children and 668 fewer child-days of delayed
      immunization; 4.6 additional health supervision visits and 5.9 additional other
      visits to the primary care provider; and 1.8 additional anemia screenings and 1.3
      additional lead screenings. CONCLUSIONS: Outreach directed toward children not up
      to-date on immunizations improves not only immunization status, but also health
      supervision visit attendance and screening rates. The cost per additional child
      immunized was high, but should be interpreted in view of the spillover benefits
      that accompanied improved immunization. Effective means to improve coverage by
      reducing missed immunization opportunities still need to be identified.

PMID- 9917437
TI  - Early prognostic indicators of outcome in infants with neonatal cerebral
      infarction: a clinical, electroencephalogram, and magnetic resonance imaging
      study.
AB  - OBJECTIVE: The aim of this study was to identify prognostic factors in newborns
      with cerebral infarction. DESIGN: Antenatal and perinatal factors and early
      clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI)
      findings were compared with neurodevelopmental outcome in 24 children with
      evidence of cerebral infarction on neonatal MRI. RESULTS: Out of 24 infants, 19
      had an infarction in the territory of a major cerebral vessel and 5 in the
      borderzone between cerebral arteries. Neuromotor outcome was normal in 17 and
      abnormal in 7 infants. Of these 7 infants, 5 infants showed a definite
      hemiplegia, whereas the other 2 showed some asymmetry of tone or function but no
      definite hemiplegia. None of the adverse antenatal or perinatal factors was
      significantly associated with abnormal outcome. Neonatal clinical examination was
      also not always predictive of the outcome. The extent of the lesion on MRI was a
      better predictor. In particular, it was the concomitant involvement of
      hemisphere, internal capsule and basal ganglia that was always associated with an
      abnormal outcome whereas the involvement of only one or two of the three tended
      to be associated with a normal outcome. EEG was also very helpful. Abnormal
      background activity either unilateral or bilateral was found in 6 infants and 5
      out of 6 developed hemiplegia. In contrast, the presence of seizure activity in
      presence of a normal background was not related to abnormal outcome. CONCLUSIONS:
      Early MRI and EEG can help to identify the infants with cerebral infarction who
      are likely to develop hemiplegia.

PMID- 9917438
TI  - Once-daily therapy for streptococcal pharyngitis with amoxicillin.
AB  - OBJECTIVE: An orally administered antimicrobial regimen for the treatment of
      group A beta-hemolytic streptococcal (GABHS) pharyngitis given once rather than
      multiple times each day would be more convenient and might result in improved
      patient compliance. The purpose of this study was to evaluate the effectiveness
      of once-daily amoxicillin in the treatment of GABHS pharyngitis. PATIENTS:
      Children presenting to a private pediatric office with GABHS pharyngitis. DESIGN:
      Patients were randomly assigned to receive orally either amoxicillin (750 mg once
      daily) or penicillin V (250 mg three times a day) for 10 days. Compliance was
      monitored by urine antimicrobial activity. OUTCOMES: Outcomes were measured by
      impact on the clinical course, eradication of GABHS within 18 to 24 hours, and
      bacteriologic treatment failure rate as determined by follow-up throat cultures 4
      to 6 and 14 to 21 days after completing therapy. GABHS isolates were serotyped to
      distinguish bacteriologic treatment failures (same serotype as initial throat
      culture) from new acquisitions (different serotypes). RESULTS: During the 16
      months of this study, 152 children between 4 and 18 years of age (mean, 9.9
      years) were enrolled; 79 children were randomly assigned to receive once-daily
      amoxicillin and 73 were assigned to receive penicillin V three times a day. The
      children in the two treatment groups were comparable with respect to age,
      duration of illness before initiation of therapy, compliance, and signs and
      symptoms at presentation. There was no significant difference in the clinical or
      bacteriologic responses of the patients in the two treatment groups at the 18- to
      24-hour follow-up visit. Bacteriologic treatment failures occurred in 4 (5%) of
      the 79 patients in the amoxicillin group and in 8 (11%) of the 73 patients in the
      penicillin V group. CONCLUSIONS: These data demonstrate that once-daily
      amoxicillin therapy is as effective as penicillin V therapy given three times a
      day for the treatment of GABHS pharyngitis, and if confirmed by additional
      investigations, once-daily amoxicillin therapy could become an alternative
      regimen for the treatment of this disease.

PMID- 9917440
TI  - Fruit juice intake is not related to children's growth.
AB  - BACKGROUND: Excessive fruit juice intake (>12 ounces/day) has been reported to be
      associated with short stature and obesity in preschool children. OBJECTIVE: To
      confirm whether excess fruit juice intake was associated with short stature and
      obesity in preschool children, we assessed growth parameters and fruit juice
      intake in 105 white children, ages 24 to 36 months. METHODOLOGY: Mothers were
      interviewed twice by a registered dietitian when children were age 24, 28, or 32
      months (interview 1) and when children were age 28, 32, or 36 months (interview
      2); interviews were assigned randomly. At each interview mothers provided 3 days
      of dietary data (one 24-hour recall and a 2-day food record) and the registered
      dietitian weighed the child and measured his/her height. Dietary data were
      analyzed using Nutritionist IV software. Each child's body mass index (wt/ht2)
      and ponderal index (wt/ht3) were calculated for each interview. Growth parameters
      of children consuming <12 ounces/day 100% fruit juice were compared with those
      consuming >/=12 ounces/day using the Student's t test, chi2, Fisher's exact test,
      and mixed model repeated measures analyses (PROC MIXED). RESULTS: Results
      consistently indicated no statistically significant differences in children's
      height, body mass index, or ponderal index related to fruit juice intake. Intakes
      of soda pop were negatively related to intakes of milk and fruit juice although
      intakes of milk and fruit juice were not related. CONCLUSIONS: The consistent
      lack of relationship between children's fruit juice intake and growth parameters
      in our study does not support previous recommendations to limit the intake of
      100% fruit juice to <12 ounces/day.

PMID- 9917439
TI  - Clinical and genetic risk factors for cystic fibrosis-related liver disease.
AB  - OBJECTIVE: The aim of this study was to define the role of possible risk factors
      for the development of cystic fibrosis (CF)-related liver disease and to analyze
      the association between liver disease and the different genotypes present in the
      Israeli CF patient population. PATIENTS AND METHODS: All patients followed at the
      seven CF centers in Israel were included in this study. Liver disease was
      determined by persistently elevated serum liver enzymes and/or bilirubin, and/or
      significant ultrasonographic changes suggestive of chronic liver disease. The
      following clinical parameters were evaluated: ethnic origin, age at assessment of
      liver function, sex, history of meconium ileus, pancreatic function, history of
      distal intestinal obstruction syndrome, pulmonary function, and cystic fibrosis
      transmembrane conductance regulator mutation analysis. RESULTS: Of the 288
      patients screened, 80 (28%) had liver disease. Of the 256 patients with
      pancreatic insufficiency, 80 (31%) had liver disease compared with none of the 32
      patients with pancreatic sufficiency. Genotype-phenotype correlation was
      performed on 207 patients carrying identified mutations that were previously
      classified according to phenotype severity. Liver disease was found in 56 (32%)
      of 173 patients carrying mutations associated with a severe phenotype and in 6
      (38%) of 16 patients carrying at least one mutation associated with a variable
      genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb
      C->T mutation had liver disease. Prevalence of liver disease increased with age.
      No correlation was found between liver disease and severity of lung disease,
      nutritional status, history of meconium ileus, or distal intestinal obstruction
      syndrome. CONCLUSION: CF patients who have pancreatic insufficiency and carry
      mutations associated with a severe or a variable genotype are at increased risk
      to develop liver disease.

PMID- 9917441
TI  - Osmoregulation and desmopressin pharmacokinetics in enuretic children.
AB  - OBJECTIVE: The aim was to compare responders and nonresponders to antienuretic
      treatment with desmopressin with respect to pharmacokinetics and renal effects of
      the drug. METHODS: Twelve children, aged 7.6 to 16.2 years, with nocturnal
      enuresis were examined. Six patients were nonresponders and 6 were responders to
      desmopressin treatment. The children were given 2 mg of desmopressin
      intravenously and plasma concentrations of the drug were monitored overnight.
      Urine parameters were followed for 24 hours after desmopressin administration.
      Ten patients also underwent a thirst provocation test. RESULTS: Desmopressin
      pharmacokinetics did not differ between the groups. Neither nocturnal urine
      production nor morning urine osmolality after desmopressin injection differed
      between responders and nonresponders, whereas the responders produced
      significantly larger amounts of significantly less concentrated urine during the
      day after the injection compared with the nonresponders (urine production, 2.02
      +/- 0.84 and 0.77 +/- 0.20 mL/kg/h; urine osmolality, 558 +/- 271 and 883 +/- 134
      mOsm/kg). Nonresponders voided with smaller bladder volumes (2.43 +/- 0.68 mL/kg
      body weight) than responders (4.70 +/- 1.21 mL/kg). The responders produced
      significantly less concentrated urine than the nonresponders during the thirst
      provocation test (607 +/- 185 and 922 +/- 217 mOsm/kg, respectively). CONCLUSION:
      Intravenous desmopressin pharmacokinetics and desmopressin renal effects did not
      differ between responders and nonresponders to desmopressin treatment.
      Nonresponders had a smaller spontaneous bladder capacity and responders produced
      less concentrated urine.

PMID- 9917442
TI  - Social, emotional, and behavioral functioning of children with cancer.
AB  - OBJECTIVE: It was hypothesized that children with cancer would have more social
      problems and difficulties with emotional well-being than case control, same
      race/gender, similarly aged classmates. STUDY DESIGN: Using a case controlled
      design, children with any type of cancer requiring chemotherapy except brain
      tumors (n = 76), currently receiving chemotherapy, ages 8 to 15, were compared
      with case control classroom peers (n = 76). Peer relationships, emotional well
      being, and behavior were evaluated based on peer, teacher, parent, and self
      report, and were compared using analysis of variance and structural equation
      modeling. RESULTS: Relative to case controls, children with cancer were perceived
      by teachers as being more sociable; by teachers and peers as being less
      aggressive; and by peers as having greater social acceptance. Measures of
      depression, anxiety, loneliness, and self-concept showed no significant
      differences, except children with cancer reported significantly lower
      satisfaction with current athletic competence. There were also no significant
      differences in mother or father perceptions of behavioral problems, emotional
      well-being, or social functioning. Scores on all standardized measures were in
      the normal range for both groups. Comparisons of the correlation matrices of
      children with cancer and to the correlation matrix of the comparison children
      using structural equation modeling suggested they were not significantly
      different. CONCLUSIONS: Children with cancer currently receiving chemotherapy
      were remarkably similar to case controls on measures of emotional well-being and
      better on several dimensions of social functioning. These findings are not
      supportive of disability/stress models of childhood chronic illness and suggest
      considerable psychologic hardiness.

PMID- 9917443
TI  - Dose-response effect of fetal cocaine exposure on newborn neurologic function.
AB  - BACKGROUND: Studies of fetal cocaine exposure and newborn neurologic function
      have obtained conflicting results. Although some studies identify abnormalities,
      others find no differences between cocaine-exposed and cocaine-unexposed infants.
      To determine the effects of prenatal cocaine exposure on intrauterine growth and
      neurologic function in infants, we prospectively evaluated 253 infants shortly
      after birth. METHODS: Women who delivered a live singleton >36 weeks by dates
      were eligible for enrollment. Maternal exclusionary criteria were known
      parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant
      exclusionary criteria were Apgar scores </=4 at 5 minutes, obvious congenital
      malformations, seizures, or strokes. A total of 98% of infants were evaluated
      between 1 to 7 days of age. Newborns were assessed with the Neurological
      Examination for Children (NEC) by a pediatric neurologist (C.A.C.) who was
      blinded to exposure status. Gestational age was determined by Ballard's
      examination. Cocaine exposure was determined for the last trimester by
      radioimmunoassay of maternal hair (RIAH). Exposure values ranged from 2 to 4457
      ng/10 mg hair. Infants were excluded if a maternal hair sample was missing (N =
      13). The sample comprises 240 woman and infant pairs-104 cocaine-exposed and 136
      cocaine-unexposed. RESULTS: Compared with unexposed controls, cocaine-exposed
      infants exhibited higher rates of intrauterine growth retardation (24% vs 8%),
      small head circumference ([HC] <10th% percentile) (20% vs 5%) and neurologic
      abnormalities: global hypertonia (32% vs 11%), coarse tremor (40% vs 15%), and
      extensor leg posture (20% vs 4%). We found increasing odds (odds ratio) of growth
      and neurologic impairment with increasing level of cocaine exposure in stratified
      analyses. The odds ratio associated with three levels of cocaine exposure (no
      exposure, low exposure = RIAH 2-66 ng/mg; and high exposure = RIAH 81-4457 ng/mg)
      respectively are: 1.0, 3.3, and 6.1 for small head size (chi2 for trend); 1.0, 3.
      3, and 4.3 for global hypertonia (chi2 for trend); 1.0, 3.4, and 7.4 for extensor
      leg posturing (chi2 for trend); and 1.0, 3.8, and 3.8 for coarse tremor (chi2 for
      trend). Significant associations between cocaine exposure and neurologic signs
      were found in logistic regression equations that controlled for 20 or more
      variables. CONCLUSION: We conclude that adverse neonatal effects associated with
      fetal cocaine exposure follow a dose-response relationship: newborns with higher
      levels of prenatal cocaine exposure show higher rates of impairments in fetal
      head growth and abnormalities of muscle tone, movements, and posture. Significant
      relationships between cocaine exposure and these outcomes remain in controlled
      analyses.

PMID- 9917444
TI  - Motor development of cocaine-exposed children at age two years.
AB  - OBJECTIVE: This article was designed to investigate effects of prenatal cocaine
      exposure on motor development of young children from a predominately
      underprivileged, urban population. METHODOLOGY: A total of 260 infants and young
      children were initially recruited from either the newborn nursery or the at-risk
      pediatric clinic of an urban teaching hospital. Prenatal history and birth
      outcomes were collected from medical records. Demographic characteristics and
      additional drug histories were obtained from the mothers. The 199 subjects (98
      cocaine-exposed and 101 unexposed) who returned at age 2 years were assessed by
      examiners blinded to drug exposure status using the Peabody Developmental Motor
      Scales. RESULTS: Compared with control subjects, the cocaine-exposed group
      performed significantly less well on both the fine and the gross motor
      development indices. Mean scores for both groups were within the average range on
      the gross motor index, but greater than 1 standard deviation below average on the
      fine motor index. Differences were significant on the balance and the receipt and
      propulsion subscales of the gross motor scale, and on the hand use and the eye
      hand coordination subscales of the fine motor scale. Cocaine status independently
      predicted poorer hand use and eye-hand coordination scores. There also was an
      effect of alcohol exposure on the receipt and propulsion subscale. CONCLUSIONS:
      Findings indicate that deficiencies in motor development remain detectable at 2
      years of age in children exposed to drugs prenatally. Although other
      environmental variables may influence motor development, children exposed to
      cocaine and to alcohol in utero may encounter developmental challenges that
      impede later achievement.

PMID- 9917445
TI  - Developmental dysplasia of the hip: a new approach to incidence.
AB  - OBJECTIVE: The controversy over the incidence of developmental dysplasia of the
      hip (DDH) stems mainly from an ambiguity of criteria for defining a genuinely
      pathologic neonatal hip. In this study, we evaluate an algorithm we devised for
      the treatment of DDH, for its ability to identify those neonatal hips which, if
      left untreated, would develop any kind of dysplasia and, therefore, are to be
      included in the determination of DDH incidence. METHODS: Clinical and
      ultrasonographic examinations for DDH were performed on 18 060 consecutive
      neonatal hips at 1 to 3 days of life. Newborns with skeletal deformities,
      neurologic/muscular disorders, and neural tube defects were excluded. Hips that
      featured any type of sonographic pathology were reexamined at 2 or 6 weeks,
      depending on the severity of the findings. Only hips in which the initial
      pathology was not improved or had deteriorated were treated; all others were
      examined periodically until the age of 12 months. RESULTS: Sonographic screening
      of 18 060 hips detected 1001 instances of deviation from normal, indicating a
      sonographic DDH incidence of 55.1 per 1000. However, only 90 hips remained
      abnormal and required treatment, indicating a true DDH incidence of 5 per 1000
      hips. All the others evolved into normal hips, and no additional instances of DDH
      were found on follow-up throughout the 12 months. CONCLUSIONS: The implementation
      of our protocol enables us to distinguish two categories of neonatal hip
      pathology: one that eventually develops into a normal hip (essentially
      sonographic DDH); and another that will deteriorate into a hip with some kind of
      dysplasia, including full dislocation (true DDH). This approach seems to allow
      for a better-founded definition of DDH, for an appropriate determination of its
      incidence, for decision-making regarding treatment, and for assessment of the
      cost-effectiveness of screening programs for the early detection of DDH.

PMID- 9917446
TI  - Evaluation of risk assessment questions used to target blood lead screening in
      Illinois.
AB  - OBJECTIVE: Beginning in 1995, Illinois law permitted targeted-as opposed to
      universal-blood lead screening in low-risk areas, which were defined by ZIP code
      characteristics. State guidelines recommended specific lead risk assessment
      questions to use when targeting screening. This study was designed to evaluate
      the sensitivity and specificity of Illinois lead risk assessment questions.
      DESIGN: Parents bringing their 9- or 10- or 12-month and 24-month-old children
      for health supervision visits at 13 pediatric practices and parents of children
      (aged 6 through 25 months and who needed a blood lead test) receiving care at 5
      local health departments completed a lead risk assessment questionnaire
      concerning their child. Children had venous or capillary blood lead testing.
      Venous confirmation results of children with a capillary level >/=10
      micrograms/dL were used in analyses. CHILDREN: There were 460 children with both
      blood and questionnaire data recruited at the pediatric practices (58% of
      eligible) and 285 children (51% of eligible) recruited at local health
      departments. Of the 745 children studied, 738 provided a ZIP code that allowed
      their residence to be categorized as in a low-risk (n = 456) or high-risk (n =
      282) area. RESULTS: Sixteen children (3.5%) living in low-risk areas versus 34
      children (12.1%) living in high-risk areas had a venous blood lead level (BLL)
      >/=10 micrograms/dL; 1.8% and 5.3%, respectively, had a venous BLL >/=15
      micrograms/dL. For children living in low-risk areas, Illinois mandated risk
      assessment questions (concerning ever resided in home built before 1960, exposure
      to renovation, and exposure to adult with a job or hobby involving lead) had a
      combined sensitivity of.75 for levels >/=10 micrograms/dL and.88 for levels >/=15
      micrograms/dL; specificity was.39 and.39, respectively. The sensitivity of these
      questions was similar among children from high-risk areas; specificity decreased
      to.27 and.28, for BLLs >/=10 micrograms/dL and >/=15 micrograms/dL, respectively.
      The combination of items requiring respondents to list house age (built before
      1950 considered high risk) and indicate exposure to renovation had a sensitivity
      among children from low-risk areas of.62 for BLLs >/=10 micrograms/dL with
      specificity of.57; sensitivity and specificity among high-risk area children
      were.82 and.36, respectively. For this strategy, similar sensitivities and
      specificities for low and high-risk areas were found for BLLs >/=15
      micrograms/dL. CONCLUSIONS: The Illinois lead risk assessment questions
      identified most children with an elevated BLL. Using these questions, the
      majority of Illinois children in low-risk areas will continue to need a blood
      lead test. This first example of a statewide screening strategy using ZIP code
      risk designation and risk assessment questions will need further refinement to
      limit numbers of children tested. In the interim, this strategy is a logical next
      step after universal screening.

PMID- 9917447
TI  - A STD/HIV prevention trial among adolescents in managed care.
AB  - OBJECTIVE: To determine if sexually transmitted diseases (STDs), including human
      immunodeficiency virus (HIV) infection, risk assessment, and education tools
      provided as part of office-based primary care reduce adolescent risky sexual
      behaviors. DESIGN: A randomized intervention trial with 3- and 9-month follow-up.
      SETTING: Five staff-model managed care sites in Washington, DC (n = 19
      pediatricians). PATIENTS: Consecutive 12- to 15-year-olds receiving a general
      health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month
      follow-up rate = 197/215 (92%). INTERVENTION: Audiotaped STD risk assessment and
      education about staying safe (safer = condoms, safest = abstinence). MAIN OUTCOME
      MEASURES: Adolescent-reported sexual intercourse and condom use. RESULTS: More
      intervention adolescents reported pediatrician discussion on 11/13 sexual topics.
      Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence
      interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months,
      this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32).
      More sexually active adolescents reported condom use in the intervention group at
      3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group
      differences in sexual behaviors; however, more signs of STD were reported by the
      control (7/103) than the intervention group (0/94). CONCLUSIONS: STD risk
      assessment and education tools administered in a single office visit facilitated
      STD/HIV prevention education. Any impact on sexual activity and condom use was
      short-lived. Further research is needed to develop brief, office-based sexual
      risk reduction for young adolescents.

PMID- 9917448
TI  - Orthostatic intolerance in adolescent chronic fatigue syndrome.
AB  - OBJECTIVES: To demonstrate the association between orthostatic intolerance and
      the chronic fatigue syndrome (CFS) in adolescents and to delineate the form that
      orthostatic intolerance takes in these children. STUDY DESIGN: We investigated
      the heart rate and blood pressure (BP) responses to head-up tilt (HUT) in 26
      adolescents aged 11 to 19 years with CFS compared with responses in adolescents
      referred for the evaluation of simple faint and to responses in 13 normal healthy
      control children of similar age. RESULTS: A total of 4/13 of the controls and
      18/26 simple faint patients experienced typical faints with an abrupt decrease in
      BP and heart rate associated with loss of consciousness. One CFS patient had a
      normal HUT. A total of 25/26 CFS patients experienced severe orthostatic symptoms
      associated with syncope in 7/25, orthostatic tachycardia with hypotension in
      15/25, and orthostatic tachycardia without significant hypotension in 3/25.
      Acrocyanosis, cool extremities, and edema indicated venous pooling in 18/25. None
      of the control or simple faint patients experienced comparable acral or
      tachycardic findings. CONCLUSIONS: We conclude that chronic fatigue syndrome is
      highly related to orthostatic intolerance in adolescents. The orthostatic
      intolerance of CFS often has heart rate and BP responses similar to responses in
      the syndrome of orthostatic tachycardia suggesting that a partial autonomic
      defect may contribute to symptomatology in these patients.

PMID- 9917449
TI  - Home-based management can achieve intensification cost-effectively in type I
      diabetes.
AB  - BACKGROUND: Newly diagnosed insulin-dependent diabetic children are most often
      admitted to hospital for education and insulin management and subsequently
      followed in outpatient clinics or office settings. However, most could be managed
      at home, given adequate family and health care team support and subsequent follow
      up facilitated by home-based nursing intervention. We conducted a randomized
      trial of clinical, psychosocial, and cost effects of home-based management in a 2
      year follow-up study of newly diagnosed diabetic children. METHODS: Sixty three
      patients were randomly assigned to traditional hospitalization and outpatient
      follow-up (hospital-based group) or home management (home-based group). Treatment
      differences between the two groups consisted of duration of initial hospital
      stay, site and timing of initial teaching, and nature and extent of subsequent
      nursing follow-up. Metabolic control was assessed by means of quarterly
      glycosylated hemoglobin measurements for 24 months and then at 36 months.
      Diabetes-related adverse events, knowledge of diabetes, adherence to the diabetes
      regimen, psychosocial impact, and social (total) costs incurred were assessed for
      24 months. FINDINGS: Glycosylated hemoglobin concentrations were significantly
      lower in the home-based group at 12 to 24 months and at 36 months. Both groups
      had comparable numbers of diabetes-related adverse events. There were no
      significant group differences in psychosocial impact. Parents in the home-based
      group spent significantly fewer hours on diabetes care and incurred significantly
      lower out-of-pocket expenses during the 1st month. Health care sector costs were
      significantly higher. Hospital costs were $889 higher, and government costs $890
      higher per child. Social (total) costs were only $48 higher per case (NS) with
      home care when parents' time was valued at $11.88 per hour. INTERPRETATION: Home
      based management for newly diagnosed diabetic children can result in better
      metabolic control and similar psychosocial outcomes compared with traditional
      hospital- and clinic-based care without notable effects on social (total) costs.

PMID- 9917450
TI  - Children, adolescents, and the media: issues and solutions.

PMID- 9917451
TI  - Developmental dysplasia of the hip: a spectrum of abnormality.

PMID- 9917452
TI  - "Doctor, if this were your child, what would you do"?

PMID- 9917453
TI  - See one, do one, teach one.

PMID- 9917454
TI  - The Jonesboro school shootings: lessons for us all.

PMID- 9917455
TI  - Advocating for children: the pediatrician's role in violence prevention.

PMID- 9917456
TI  - Central anticholinergic syndrome on therapeutic doses of cyproheptadine.

PMID- 9917457
TI  - Saphenous nerve entrapment in adolescence.

PMID- 9917458
TI  - Disclosure of illness status to children and adolescents with HIV infection.
      American Academy of Pediatrics Committee on Pediatrics AIDS.
AB  - Many children with human immunodeficiency virus (HIV) infection and acquired
      immunodeficiency syndrome are surviving to middle childhood and adolescence.
      Studies suggest that children who know their HIV status have higher self-esteem
      than children who are unaware of their status. Parents who have disclosed the
      status to their children experience less depression than those who do not. This
      statement addresses our current knowledge and recommendations for disclosure of
      HIV infection status to children and adolescents.

PMID- 9917459
TI  - Culturally effective pediatric care: education and training issues. American
      Academy of Pediatrics Committee on Pediatric Workforce.
AB  - This policy statement defines culturally effective health care and describes its
      importance for pediatrics. The statement also defines cultural effectiveness,
      cultural sensitivity, and cultural competence and describes the importance of
      these concepts for training in medical school, residency, and continuing medical
      education. The statement is based on the premise that culturally effective health
      care is important and that the knowledge and skills necessary for providing
      culturally effective health care can be taught and acquired through 1)
      educational courses and other formats developed with the expressed purpose of
      addressing cultural competence and/or cultural sensitivity, and 2) educational
      components on cultural competence and/or cultural sensitivity that are
      incorporated into medical school, residency, and continuing medical education
      curricula.

PMID- 9917460
TI  - Poliomyelitis prevention: revised recommendations for use of inactivated and live
      oral poliovirus vaccines. American Academy of Pediatrics Committee on Infectious
      Diseases.
AB  - Since 1997 when the American Academy of Pediatrics (AAP) issued revised
      guidelines for the prevention of poliomyelitis, substantial progress in global
      eradication of poliomyelitis has occurred and the use of inactivated poliovirus
      vaccine (IPV) has increased considerably in the United States with a
      corresponding decrease in the use of oral poliovirus vaccine (OPV). Surveys
      indicate that the majority of physicians now routinely immunize children with the
      sequential IPV-OPV or IPV-only regimens. Nevertheless, vaccine-associated
      paralytic poliomyelitis (VAPP) continues to occur, albeit infrequently, in
      children who have received the OPV-only regimen and their contacts. To reduce
      further the risk of VAPP, the AAP now recommends that children in the United
      States receive IPV for the first 2 doses of the polio vaccine series in most
      circumstances. Exceptions include a parent's refusal to permit the number of
      injections necessary to administer the other routinely recommended vaccines at
      the 2- and 4-month visits. Either IPV or OPV can be administered for the third
      and fourth doses. Assuming continuing progress toward global eradication, a
      recommendation of IPV-only immunization for children in the United States is
      anticipated by 2001.

PMID- 9917461
TI  - The role of the pediatrician in youth violence prevention in clinical practice
      and at the community level. American Academy of Pediatrics Task Force on
      Violence.
AB  - Violence and violent injuries are a serious threat to the health of children and
      youth in the United States. It is crucial that pediatricians define their role
      and develop the appropriate skills to address this threat effectively. From a
      clinical perspective, pediatricians should incorporate into their practices
      preventive education, screening for risk, and linkages to necessary intervention
      and follow-up services. As advocates, pediatricians should become involved at the
      local and national levels to address key risk factors and assure adequacy of
      preventive and treatment programs. There are also educational and research needs
      central to the development of effective clinical strategies. This policy
      statement defines the emerging role of pediatricians in youth violence prevention
      and management. It reflects the importance of this issue in the strategic agenda
      of the American Academy of Pediatrics for promoting optimal child health and
      development.

PMID- 9917462
TI  - Recommended childhood immunization schedule-United States, January-December 1999.
      American Academy of Pediatrics Committee on Infectious Diseases.

PMID- 9917463
TI  - Guidelines for the evaluation of sexual abuse of children: subject review.
      American Academy of Pediatrics Committee on Child Abuse and Neglect.
AB  - This statement serves to update guidelines for the evaluation of child sexual
      abuse first published in 1991. The role of the physician is outlined with respect
      to obtaining a history, physical examination, and appropriate laboratory data and
      in determining the need to report sexual abuse.

PMID- 9917464
TI  - Quality improvement methods in clinical medicine.
AB  - This article surveys the methods and tools of quality improvement used today in
      health care. Specifically, we describe how clinicians can use these methods to
      impact the clinical practice of medicine. Improvement teams from a variety of
      health care organizations have reported the successful use of basic methods such
      as group work, flowcharting, data collection, and graphical data analysis. In
      addition to these incremental, problem-solving methods borrowed from the
      industrial practice of improvement, we have also seen the use of specific process
      design methods in health care applications such as care path development. The
      pace of change in health care has also led to the practical development of newer
      methods for rapid cycle improvement. We will review the basic approach behind
      these methods and illustrate key elements such as the ideas of change concepts
      and small-scale tests of change. Unfortunately, whereas these methods have been
      very successful and highly appealing to improvement practitioners, they may also
      have inadvertently widened a gulf between these practitioners and traditional
      health-services and clinical researchers. We offer an assessment of this issue
      and suggest ways to narrow the communication gap. Measurement has also
      traditionally been a part of the thinking about quality assurance and improvement
      in health care. We review the new philosophy of measurement that has emerged from
      recent improvement thinking and describe the use of control charts in clinical
      improvement. Benchmarking and multiorganizational collaboratives are more recent
      innovations in the ways we approach improvement in health care. These efforts go
      beyond simple measurement and explore the why and how associated with the
      widespread variation in performance in health care. We explore a variety of
      health care examples to illustrate these methods and the lessons learned in their
      use. We conclude the article with an overview of four habits that we believe are
      essential for health care organizations and individual clinicians to adopt to
      bring about real improvement in the clinical practice of medicine. These are the
      habits for: 1) viewing clinical practice as a process; 2) evidence-based
      practice; 3) collaborative learning; and 4) change.

PMID- 9917465
TI  - The principles and practice of evidence-based neonatology.
AB  - Significant strides toward improving the outcome of newborn infants have been
      observed during the modern era of neonatal-perinatal medicine. One of the
      challenges that neonatologists and pediatricians face is deciding when to change
      current practices. New literature is abundant, but it must be critically reviewed
      and evaluated before changes in practice are made. The evidence-based medicine
      process can be used to help in changing practices or adopting new practices. It
      is based on five steps: 1) forming answerable questions; 2) searching for the
      best evidence; 3) critically appraising the evidence; 4) applying the evidence in
      practice; and 5) evaluating one's performance. This article reviews the five
      steps of the evidence-based medicine process. The various levels of evidence,
      including randomized, controlled trials and systematic reviews, are defined and
      discussed. An example of a critically appraised topic, a practical tool that can
      be used as an aid in addressing the first three questions of the evidence-based
      medicine process, is included. Once the evidence has been evaluated, the decision
      of whether or not to implement a change in individual practice or in
      institutional guidelines must be made. These decisions are difficult and require
      a variety of individual and societal factors to be taken into account. Examples
      of evidence-based medicine in neonatal and perinatal medicine include the use of
      antenatal corticosteroids for promotion of lung maturity, the use of surfactant
      replacement therapy for the treatment and prevention of respiratory distress
      syndrome, and prophylactic indomethacin for the prevention of intraventricular
      hemorrhage. Review of these examples provides insight into the strengths and
      weaknesses of evidence-based medicine.

PMID- 9917466
TI  - Evidence-based guidelines and critical pathways for quality improvement.
AB  - Clinical practice guidelines have a long and distinguished tradition in
      pediatrics. Currently, the American Academy of Pediatrics has developed more than
      15 practice guidelines and more than 250 clinical policy statements. In the past,
      practice guidelines have been used to improve care through the dissemination of
      evidence-based, clinically effective practices to pediatric practitioners. In the
      current environment this purpose has been broadened to include cost reduction,
      standardization of practice, and reduction of medical liability. This has led to
      both confusion and distrust on the part of the pediatrician. Practice guidelines
      are best understood as a tool to insure that children receive evidence-based
      care. They are best used in association with a set of outcome and performance
      measures that provide feedback to clinicians and allow for modification of the
      guidelines to meet the needs of the local patient population. The quality of
      practice guidelines is directly dependent on the quality of the medical evidence
      supporting the recommendation. Unfortunately only a small percentage of the
      evidence supporting practice guidelines comes from randomized clinical trials
      with the majority of the evidence coming from expert clinical panels. The success
      of practice guidelines in improving care for children has yet to be convincingly
      demonstrated. Currently, there is a dearth of well designed studies that document
      the effectiveness of practice guidelines. Their ultimate effectiveness will
      depend on both an improved evidence base and effective strategies for rapid
      dissemination of the recommendations. The development of evidence-based practice
      guidelines does not insure that it will have a major impact on physician
      practice. In the past, effective dissemination of new knowledge has been a long
      process, often taking years. This cycle time can be dramatically shortened
      through the development of networks of practice sites that share knowledge and
      experience in the implementation of practice guidelines and the use of strategies
      that take advantage of key groups in the dissemination process. When used
      appropriately, practice guidelines can provide an important adjunct to clinical
      research by facilitating the dissemination of new clinical findings and can
      provide an important platform for encouraging innovations in patient care.

PMID- 9917467
TI  - State health agencies and quality improvement in perinatal care.
AB  - The origin of the federal-state partnership in Maternal and Child Health (MCH)
      can be traced from the Children's Bureau grants of 1912, through the Sheppard
      Towner Act, to the creation of Title V and other programs of today that mandate
      planning, accountability, and systems development. In the past decade with the
      transformation of the health care system and the emergence of managed care, there
      has been a resurgence of interest in public, professional, and governmental
      interest in quality measurement and accountability. Regional perinatal systems
      have been implemented in all states with varying levels of involvement by state
      health agencies and the public sector. This historical framework discusses two
      primary themes: the decades of evolution in the federal-state partnership, and
      the emergence in the last three decades of perinatal regional system policy, and
      suggests that the structure of the federal-state partnership has encouraged state
      variation. A survey of state MCH programs was undertaken to clarify their
      operational and perceived role in promoting quality improvement in perinatal
      care. Data and information from the survey, along with five illustrative state
      case studies, demonstrate great variation in how individual state agencies
      function. State efforts in quality improvement, a process to make things better,
      have four arenas of activity: policy development and implementation, definition
      and measurement of quality, data collection and analysis, and communication to
      affect change. Few state health agencies (through their MCH programs and
      perinatal staff) are taking action in all four arenas. This analysis concludes
      that there are improvements MCH programs could implement without significant
      expansion in their authority or resources and points out that there is an
      opportunity for states to be more proactive as they have the legal authority and
      responsibility for assuring MCH outcomes.

PMID- 9917468
TI  - Using employer purchasing power to improve the quality of perinatal care.
AB  - Large employers have become increasingly involved in helping to set the agenda
      for quality measurement and improvement. Moreover, they are beginning to hold
      health care organizations accountable for their performance through marketplace
      incentives, including the public reporting of comparative quality data and the
      linkage of reimbursement to performance on quality measures. The Pacific Business
      Group on Health (PBGH) is an employer coalition that has been prominent in
      establishing models for collaborative quality measurement and improvement in the
      California marketplace. PBGH's involvement in quality stems from an environment
      in which purchasers were faced with high health care costs, yet virtually no
      information with which to assess the value their employees received from that
      care. Research indicating widespread variation in performance across health care
      organizations and seemingly limited oversight for quality of care within the
      industry has further motivated purchasers' efforts to better understand the
      quality of care being delivered to their em-ployees. Using the purchasing power
      of employers representing 2.5-million covered lives, PBGH endeavors to encourage
      the transition of the health care marketplace from one that competes solely on
      price to one that competes on price and quality. This entails collaborating with
      the health care industry to develop and publicly report valid performance data
      for use by both large employers and consumers of health care services. It also
      includes communicating to the marketplace purchasers' commitment to making
      purchasing decisions based on quality as well as cost. PBGH efforts to measure,
      report, and improve quality have been demonstrated by several undertakings in the
      perinatal care arena, including research to assess cesarean section rates and
      newborn readmission rates across California hospitals.employer coalition,
      purchaser, quality measurement, quality improvement, report cards, perinatal
      quality of care.

PMID- 9917469
TI  - Risk adjustment for quality improvement.
AB  - We can learn what is achievable with current technologies by comparing our
      neonatal intensive care unit outcomes with others. Because neonatal intensive
      care units may vary with respect to their case-mix, risk adjustment is essential
      to making fair comparisons in any research that does not equalize risks through
      randomization. Risk adjustment first requires strict definition of each specific
      outcome. Then each risk factor is measured and weighted accordingly. Severity of
      illness scores are a special form of risk adjustment. The leading newborn illness
      severity scores rely on physiology-based items from bedside vital signs and
      laboratory tests. The mechanics of score development are discussed including item
      selection, definition, collection, and potential biases. The process of weighting
      risk factors usually involves building multivariate models. Issues of derivation,
      validation, discrimination, calibration, and reliability affect the utility of
      all scores. Once a comparison is appropriately risk-adjusted, there are important
      cautions about interpretation, including the source of the reference (benchmark)
      population, sample size, and biases from incomplete risk adjustment. Nonetheless,
      these findings can spur quality improvement efforts that can lead to dramatic,
      system-wide improvements in outcomes.

PMID- 9917470
TI  - Perinatal information systems for quality improvement: visions for today.
AB  - Today clinical information is used for a multitude of purposes beyond patient
      care documentation including quality review and improvement processes, allocation
      of resources, budgetary and long-term planning, productivity measurement, and
      justification to payers for services provided. Providers in perinatal medicine
      are faced with the challenge of finding methods to meet these information needs.
      Case examples of the different approaches to collecting and using obstetric and
      neonatal information are described. The role of computer-based patient records is
      outlined and solutions available to perinatal medicine are reviewed.

PMID- 9917471
TI  - Vital records for quality improvement.
AB  - The birth certificate and death certificate are important sources of population
      based data for assessing the extent of risk and the quality of perinatal outcome.
      The birth certificate contains the hospital of birth and many items, such as
      birth weight and race, that can serve as important risk adjusters for neonatal
      mortality. To assess mortality a second vital record, the death certificate, must
      be linked to the birth certificate. If the analysis is to be stratified by level
      of neonatal care or other hospital characteristics, a third file providing these
      details must also be utilized. The exact vital record formats, recording
      protocols, and quality control efforts are determined by and differ across each
      state. Even with these differences, the quality and completeness of vital records
      and their linkage are reasonable for population-based analyses. Although the most
      important vital outcome from a neonatologist's perspective is neonatal mortality,
      vital records can also be used to assess fetal, perinatal, postneonatal, and
      infant mortality. The analytic paradigm that is used in quality analysis
      performed on data derived from the vital record states that observed outcome is a
      function of risk, chance, and care. Risk is a characteristic or condition such as
      low birth weight or low 1-minute Apgar score that elevates the probability of an
      adverse outcome but is beyond the control of the agent responsible for the
      outcome. Using risk matrices or regression analysis one determines the expected
      mortality for a specific institution's case-mix. This expectation is usually
      based on the statewide analysis of infants with a similar risk profile. A
      standardized mortality ratio is calculated by dividing observed by expected
      mortality. A hospital with a high observed mortality (12 deaths per 1000) and an
      even higher expected mortality based on the risk characteristics of its neonates
      (24 per 1000) would have a standardized mortality ratio of 0.5. Once the effects
      of chance have been accounted for by statistical testing this finding could
      indicate that mortality in this hospital is 50% lower then expected. Although
      initially intended for legal and broad-based public health purposes, vital
      records represent an important source of data to inform perinatal quality
      improvement activities. The optimal usefulness of information derived from vital
      records requires that clinicians take an active role in assuring that data entry
      is complete and accurately reflects risk status, clinical factors, and outcomes.
      However, even a superb database will be of limited usefulness unless it is linked
      to an initiative that actively involves clinicians committed to quality
      improvement.

PMID- 9917472
TI  - Administrative data for quality improvement.
AB  - This article discusses the use of administrative data for quality improvement in
      perinatal and neonatal medicine. We review the nature of administrative data and
      focus on hospital discharge abstract data as the primary source of hospital- and
      community-based assessments. Although discharge abstract data lack the richness
      of primary data, these data are the most accessible comparative data source for
      examining all patients admitted to a hospital. When aggregated to the state level
      as occurs in more than 30 states, hospital discharge data reflects hospital
      utilization and outcomes for an entire geographic population at the state and
      community level. This article reviews some of the weaknesses of administrative
      data and then focuses how these data can be used for hospital- and community
      based assessment of perinatal care citing as examples the measures of perinatal
      process and outcome used by the National Perinatal Information Center in its
      Quality/Efficiency Reports for member hospitals and a study of perinatal high
      risk care in the State of Florida. The use of discharge abstract data for
      performance measurement at either the hospital or the system level requires a
      thorough understanding of how to select a patient group, its characteristics, the
      intervention, and the outcomes relevant to that patient group. In the perinatal
      arena, the National Perinatal Information Center has selected and presents those
      measures that rely on data items shown to be the most reliable based on validity
      studies and clinician opinion, delineation of the intervention, and the
      measurement of what occurred. As hospitals respond to the recent pressures of the
      Joint Commission on Accreditation of Healthcare Organizations and other quality
      assurance entities, the accuracy of the discharge data will improve. With
      accepted caution, these data sets are invaluable to researchers studying
      comparative populations over time or across large geographic areas.

PMID- 9917473
TI  - Structure and performance of different DRG classification systems for neonatal
      medicine.
AB  - There are a number of Diagnosis-Related Group (DRG) classification systems that
      have evolved over the past 2 decades, each with their own strengths and
      weaknesses. DRG systems are used for case-mix trending, utilization management
      and quality improvement, comparative reporting, prospective payment, and price
      negotiations. For any of these applications it is essential to know the accuracy
      with which the DRG system classifies patients, specifically for predicting
      resource use and also mortality. The objective of this study was to assess the
      adequacy of the three most commonly used DRG systems for neonatal patients
      Medicare DRGs, All Patient Diagnosis-Related Groups (AP-DRGs), and All Patient
      Refined Diagnosis-Related Groups (APR-DRGs). A 2-part methodology is used to
      assess adequacy. The first part is a descriptive analysis that examines the
      structural characteristics of each system. This provides a framework for
      understanding the inherent strengths and weaknesses of each system and for
      interpreting their statistical performance. The second part examines the
      statistical performance of each system on a large nationally representative
      hospital database. The analysis identifies major differences in the structure and
      statistical performance of the three DRG systems for neonates. The Medicare DRGs
      are structurally the least developed and yield the poorest overall statistical
      performance (cost R2 = 0.292; mortality R2 = 0.083). The APR-DRGs are
      structurally the most developed and yield the best statistical performance (cost
      R2 = 0.627; mortality R2 = 0.416). The AP-DRGs are intermediate to Medicare DRGs
      and APR-DRGs, although closer to APR-DRGs (cost R2 = 0.507; mortality R2 =
      0.304). An analysis of payment impacts and systematic effects identifies there
      are major systematic biases with the Medicare DRGs. At the patient level, there
      is substantial underpayment for surgical neonates, transferred-in neonates,
      neonates discharged to home health services, and neonates who die. In contrast,
      there is substantial overpayment for normal newborns. At the facility level,
      there is substantial underpayment for freestanding acute children's hospitals and
      major teaching general hospitals. There is overpayment for other urban general
      hospitals but this pattern varies by hospital size. There is very substantial
      overpayment for other rural hospitals. The AP-DRGs remove the majority of the
      systematic effects but significant biases remain. The APR-DRGs remove most of the
      systematic effects but some biases remain.

PMID- 9917474
TI  - Consideration of the use of health status, functional outcome, and quality-of
      life to monitor neonatal intensive care practice.
AB  - Measures of health status, functional abilities, and quality-of-life are being
      used increasingly to evaluate health care practice, and to measure outcomes from
      the patient's perspective. There is thus a need to reassess the use of growth and
      neurodevelopmental status that have traditionally been used as measures of
      outcome after neonatal intensive care. The quality of neonatal intensive care
      constitutes only one factor among many that determine the functional health and
      quality-of-life of survivors of neonatal intensive care. These include genetic
      disposition, intrauterine events, the effects of sociodemographic factors on the
      health and development of the child, and on the parents' assessment of their
      child's functioning. To obtain health status, functional and quality-of-life
      measures, parents need to act as proxy for the child during infancy and
      childhood. The parents' cultural, social, and educational background and the
      specific experience of the parent with children may influence their responses.
      Furthermore, their perspective may differ from that of the child. Measures that
      have been used or have the potential to measure health status, functioning, and
      quality-of-life include the National Health Interview Survey, the National Health
      Insurance Study, the Functional Status II, the Multi-Attribute Health System, the
      Functional Independence Measure for Children, the Vineland Adaptive Behavior
      Scales, the Adolescent Child Health and Illness Profile, and the Child Health
      Questionnaire for children, infants, and toddlers. Knowledge of the validity of
      the use of these measures among survivors of neonatal intensive care is, however,
      sparse. Studies have shown that the collection of a standard core of data from
      various national sources with specific criteria for defining severe disability at
      2 years of age is feasible in Great Britain. However, questionnaires or available
      national databases provide global and epidemiologic information on outcomes
      rather than identifying the specific pathogenesis or rates of impairments. To
      determine the possible deleterious effects of new therapies, specific diseases or
      impairments will need to be identified rather than the global effect on
      functioning or health related quality-of-life. Examination of the proximal
      neonatal impairments that predispose to later disability, such as rates of
      periventricular hemorrhage or retinopathy of prematurity, are probably better
      measures for evaluating quality of neonatal care rather than distal impairments
      such as cerebral palsy, growth impairments, or reactive airway disease. The
      ultimate goal of neonatal intensive care is to provide survival without
      impairment. Objective measures of specific impairments and their residual
      disability are thus better measures of the quality of neonatal intensive care
      than subjective assessments of children and their families.

PMID- 9917475
TI  - Measuring the cost of neonatal and perinatal care.
AB  - This article provides an overview of neonatal intensive care unit (NICU)
      treatment costs. It discusses data sources as well as the methods for measuring
      costs, contrasting the strengths and weaknesses of alternate approaches. In
      addition, detailed information on NICU treatment costs is presented from a
      nationally representative sample of 25 hospitals with NICUs. The sample consists
      of 3288 very low birth weight infants (</=1500 g at birth) with admission dates
      between January 1, 1993, and September 30, 1994. Information on median treatment
      cost per infant, ancillary costs, accommodation costs, length of stay, and cost
      per day are presented. In addition, ancillary costs are disaggregated further
      into those for respiratory therapy, laboratory, radiology, pharmacy, and all
      other ancillary services.

PMID- 9917476
TI  - Neonatal intensive care: satisfaction measured from a parent's perspective.
AB  - Health care systems today are complex, technically proficient, competitive, and
      market-driven. One outcome of this environment is the recent phenomenon in the
      health care field of "consumerism." Strong emphasis is placed on customer
      service, with organized efforts to understand, measure, and meet the needs of
      customers served. The purpose of this article is to describe the current
      understanding and measurement of parent needs and expectations with neonatal
      intensive care services from the time the expectant parents enter the health care
      system for the birth through the discharge process and follow-up care. Through
      literature review, 11 dimensions of care were identified as important to parents
      whose infants received neonatal intensive care: assurance, caring, communication,
      consistent information, education, environment, follow-up care, pain management,
      participation, proximity, and support. Five parent satisfaction questionnaires
      the Parent Feedback Questionnaire, Neonatal Index of Parent Satisfaction,
      Inpatient Parent Satisfaction-Children's Hospital Minneapolis, Picker Institute
      Inpatient Neonatal Intensive Care Unit Survey, and the Neonatal Intensive Care
      Unit-Parent Satisfaction Form-are critically reviewed for their ability to
      measure parent satisfaction within the framework of the neonatal care delivery
      process. An immense gap was found in our understanding about what matters most
      and when to parents going through the neonatal intensive care experience.
      Additional research is required to develop comprehensive parent satisfaction
      surveys that measure parent perceptions of neonatal care within the framework of
      the care delivery process.

PMID- 9917477
TI  - The Vermont Oxford Network: evidence-based quality improvement for neonatology.
AB  - The Vermont Oxford Network is a voluntary collaborative group of health
      professionals committed to improving the effectiveness and efficiency of medical
      care for newborn infants and their families through a coordinated program of
      research, education, and quality-improvement projects. In support of these
      activities, the Network maintains a clinical database of information about very
      low birth weight infants that now has more than 300 participating neonatal
      intensive care units (NICUs). We anticipate that these NICUs will submit data for
      25 000 infants with birth weights of 401 to 1500 g born in 1998. The research
      program of the Network includes outcomes research and randomized clinical trials.
      The goal of Network outcomes research is to identify and explain the variations
      in clinical practice and patient outcomes that are apparent among NICUs. Network
      trials are designed to answer practical questions of importance to practitioners
      and families using pragmatic designs that can be integrated into the daily
      practice of neonatology. Quality improvement is a major focus of the Network.
      Members receive confidential quarterly and annual reports based on the Network
      database that document their performance and compare practices and outcomes at
      their unit with those at other units within the Network. These reports are
      intended to assist the members in identifying opportunities for improvement and
      to help them monitor the success of their improvement efforts. Although
      information is necessary for improvement to occur, it is not sufficient to foster
      lasting improvement by itself. Information must be translated into action. The
      Network is sponsoring an ongoing program of quality initiatives designed to
      provide members with the knowledge, skills, tools, and resources needed to foster
      action for improvement. The Network's first formal quality-improvement project,
      the NIC/Q Project, brought together 10 NICUs to apply the methods of
      collaborative improvement and benchmarking to neonatal intensive care. Building
      on the lessons learned in that initial project, the Network now is conducting the
      Vermont Oxford Network Evidence-Based Quality Improvement Collaborative for
      Neonatology, known as NIC/Q 2000. This 2-year collaborative will assist
      multidisciplinary teams from the 34 participating NICUs to develop four key
      habits for improvement: the habit for change, the habit for practice as a
      process, the habit for collaborative learning, and the habit for evidence-based
      practice. During the collaborative, participants will contribute to a knowledge
      bank of clinical, organizational, and operational change ideas for improving
      neonatal care. The coordinated program of research, education, and quality
      improvement described in this article is only possible because of the voluntary
      efforts of the members. The Network will continue to support these efforts by
      developing and providing improved tools and resources for the practice of
      evidence-based neonatology.neonatology, very low birth weight, database, network,
      quality improvement, evidence-based medicine, randomization, trials, outcomes,
      mortality, length of stay.

PMID- 9917478
TI  - The neonatal "sepsis work-up": personal reflections on the development of an
      evidence-based approach toward newborn infections in a managed care organization.
AB  - "Rule out sepsis" may be the most common discharge diagnosis among infants
      admitted to the neonatal intensive care unit. Although the frequency of sepsis,
      meningitis, and other confirmed bacterial infections has remained constant
      (between 1 and 5/1000 live births) for many years, the number of infants
      evaluated and treated is much higher. Each year in the United States, as many as
      600 000 infants experience at least one evaluation for suspected bacterial
      infection during the birth hospitalization. The number treated is estimated at
      130 000 to 400 000 per year. Despite massive overtreatment, delayed diagnosis
      still occurs. The Kaiser Permanente Medical Care Program (KPMCP) considers
      developing and implementing an evidence-based approach to "rule out sepsis," a
      research and operational priority. To achieve these goals, it is essential to
      consider two key aspects of the problem. First, it is important to adopt a
      phenomenologic approach that takes clinicians' personal experience into account.
      This must include reflection on those aspects of experience often considered
      "irrational" or "subjective." Second, incorporation of a phenomenologic approach
      needs to be tempered with sound epidemiologic methods. If one considers these two
      aspects-physician experience and sound epidemiology-it is clear that much of the
      existing literature on "rule out sepsis" is of limited utility. Consequently, the
      KPMCP has conducted its own studies. These are aimed at characterizing the
      "sepsis work-up," developing electronic datasets that would permit clinicians to
      simulate various strategies, and developing techniques for ongoing electronic
      monitoring. This article summarizes the approach taken by the KPMCP Division of
      Research. It describes the results of a pilot study as well as the development
      and use of a dedicated neonatology outcomes database, the Kaiser Permanente
      Neonatal Minimum Data Set (NMDS). The NMDS database includes the Score for
      Neonatal Acute Physiology and permits ongoing monitoring of sepsis "work-ups" as
      well as confirmed cases of neonatal infection. The article also describes how the
      experience from the pilot as well as the NMDS was incorporated in the design of a
      much larger study on "rule out sepsis." Finally, the article describes some
      important theoretic issues affecting decision rule development and the use of
      computer simulations in neonatology. These issues are 1) how one handles possible
      overanalysis of a dataset; 2) how one handles data points that are unstable (eg,
      the absolute neutrophil count, which can vary considerably depending on age and
      sampling conditions); and 3) the limitations of decision rules based on computer
      simulations.

PMID- 9917479
TI  - Reducing cesarean birth rates with data-driven quality improvement activities.
AB  - Reduction of cesarean section rates has been a difficult process that has not
      been easily accomplished by the institution of guidelines. It is more a process
      of changing physician behavior rather than of medical education. This article
      analyzed the role of intensive feedback of outcomes to bring about such changes.
      Two large private obstetric services in San Francisco, CA, were studied.
      Intensive outcomes feedback using a computerized information system, The
      Perinatal Data Center, regarding cesarean birth rates and a variety of obstetric
      outcomes was provided to the medical and nursing staff at one hospital. The other
      center served as a control. After the first observation period, the outcomes
      system was introduced to the second hospital. Finally, "open label" feedback,
      intradepartmental release of everyone's key statistics with names attached, was
      performed. Active management of labor was not practiced at either hospital.
      Results. Cesarean birth rates were stable in the baseline period from 1980
      through 1988 at 24% to 25%. Introduction of the Perinatal Data Center outcomes
      system was associated with a reduction to 21% at the first hospital with no
      change in the control hospital. Subsequent introduction of the system 3 years
      later in the control hospital resulted in a decline from 25% to 20.5%. After
      merger of the two obstetric units and the institution of "open label" feedback,
      an additional decline to 18.5% was observed. Conclusion. Physician practice
      patterns and cesarean birth rates can be altered with the intensive use of
      comparative outcome data and strong physician leadership. Nonblinded,
      intradepartmental distribution of outcomes is an even more effective tool.

PMID- 9917480
TI  - Improving care through collaboration.
AB  - The opportunity to improve health care using existing scientific knowledge is
      immense. Much is known that is not being used in routine care, leading to a large
      gap between knowledge and practice. Collaborative improvement models bring health
      care professionals together to focus on this gap and to accelerate the pace of
      improvement in their organizations. This article describes one such model, the
      Institute for Healthcare Improvement's Breakthrough Series Collaborative model.
      Lessons are drawn to help inform future collaborative efforts that focus on the
      improvement of care.

PMID- 9917481
TI  - The home environment and salmonellosis in children.
AB  - OBJECTIVE: To explore the role of foods and the home environment in the
      development of Salmonella infections in infants and children. METHODS: Home
      investigations were conducted of patients younger than 4 years of age infected
      with Salmonella. Cultures were obtained from foods, persons residing in the home,
      animals/pets/insects, and environmental sources. Like serotypes encountered in
      the index patients and isolates from the home underwent typing with pulsed-field
      gel electrophoresis. RESULTS: Home inspections were conducted in approximately
      66% of eligible homes on the average of 3.4 days after the confirmation of the
      Salmonella isolate. A total of 526 cultures from 50 homes were obtained from
      foods (120), household members (73), refrigerators (52), water (47), countertops
      (46), soil (42), can-openers (36), vacuum cleaners (34), animals/pets/insects
      (26), and others (50). Isolates with a serotype identical to those in the index
      patient were found in 16 homes, 3 of which included an isolate of a second
      serotype, and an isolate of a different serotype was recovered in 3 homes. The
      pulsed-field gel electrophoresis patterns of the isolates of identical serotypes
      from the subjects and from their environment were indistinguishable in all but 2
      patients. Among isolates of the same serotype encountered in different homes, all
      patterns were different. The identical serotype was found in multiple locations
      (4), dirt surrounding front doors (4), household members (3), vacuum cleaner (1),
      animals/pets/insects (1), and a refrigerator shelf (1). CONCLUSIONS: These data
      illustrate the importance of the child's environment in the development of
      salmonellosis. Clinicians should concentrate on educating the parents about the
      environmental spread of Salmonella. Contaminated foods in the home play a less
      significant role in the infection of infants and children.

PMID- 9917482
TI  - Epidemic of gastrointestinal tract infection including hemorrhagic colitis
      attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high
      school in Japan.
AB  - BACKGROUND: An epidemic of gastrointestinal disturbances related to food
      ingestion occurred at a junior high school in Komatsu, Japan, and was caused by
      specifically Shiga toxin (Stx) 1-producing Escherichia coli O118:H2, which has
      not been reported previously in humans. No outbreak of E coli-producing Stx 1
      alone had occurred. METHODS: A total of 526 students and 35 adult staff members
      who ate the same food at lunch in the school were investigated. Questionnaires
      about food consumption at lunch were given to all 561 subjects as well as to
      clinics and hospitals that had treated 79 patients. Stool specimens from 525
      subjects, and food, water, and environmental specimens, including cooking
      utensils, were collected in an attempt to identify the pathogen. RESULTS: A total
      of 126 subjects (22.5%) developed a diarrheal illness. The pathogen was isolated
      from the stool in 131 subjects, 49 of which were asymptomatic, and from a dipper.
      Salads served over several days were identified as high-risk from food analysis.
      Gastrointestinal symptoms resembled those associated with previous infections of
      Stx-producing E coli, but were mild. No cases of the hemolytic-uremic syndrome
      developed. Headache was present in 87 patients. Three patients underwent surgery
      for acute appendicitis during this epidemic. Four of five carriers had received
      an antibiotic effective against the pathogen. CONCLUSIONS: This outbreak of E
      coli O118:H2 demonstrated the clinical and epidemiologic features of infection by
      E coli that produces Stx 1 alone. Infections with such organisms are being
      recognized increasingly, and the pattern of disease observed may differ from the
      pattern observed with E coli O157:H7.

PMID- 9917483
TI  - Perinatal risk factors for infant hospitalization with viral gastroenteritis.
AB  - CONTEXT: A tetravalent vaccine against rotavirus, the most commonly identified
      etiologic agent of viral gastroenteritis (GE), has recently been licensed for use
      in the United States. OBJECTIVE: To evaluate whether specific groups of infants
      might be at sufficiently high risk to warrant a focused rotavirus vaccine policy,
      we investigated perinatal risk factors for hospitalization with viral GE and
      rotavirus in the first year of life. DESIGN: Population-based, case-control
      study. SETTING: Washington State linked birth certificate and hospital discharge
      abstracts from 1987 through 1995. PATIENTS: Infants, 1 through 11 months of age,
      hospitalized for viral GE (N = 1606) were patients in this study. Control
      subjects were 8084 nonhospitalized infants, frequency-matched to patients on year
      of birth. PRIMARY OUTCOME MEASURE: Maternal and infant characteristics associated
      with infant hospitalization for viral GE. RESULTS: We found a significant
      association between birth weight and the risk for hospitalization. Very low birth
      weight infants (<1500 g) were at the highest risk (odds ratio [OR] 2.6; 95%
      confidence interval [CI]: 1.6,4.1);, low birth weight infants (1500-2499 g), at
      intermediate risk (OR 1.6; 95% CI: 1.3,2.1); and large infants (>4000 g), at
      reduced risk (OR 0.8; 95% CI: 0.6,0.9). Other characteristics associated with GE
      hospitalization were male gender (OR 1.4; 95% CI: 1.3,1.6); maternal smoking (OR
      1.2; 95% CI: 1.1,1. 4); unmarried mother (OR 1.2; 95% CI: 1.1,1.4); Medicaid
      insurance (OR 1.4; 95% CI: 1.3,1.7); and maternal age <20 years (OR 1.2; 95% CI:
      1.0,1.5). Infants born October through December were at decreased risk for
      hospitalization (OR 0.8; 95% CI: 0.7,0.9), as were infants born to Asian mothers
      (OR 0.5; 95% CI: 0.3,0.7), and infants born to mothers >34 years of age (OR 0.7;
      95% CI: 0.6,0.9). Using these factors, the area under a receiver operating
      characteristic curve was 0.63. Therefore, to achieve a sensitivity of 90% in
      identifying high-risk infants, specificity would fall to 10%. Subanalyses of
      children admitted for viral GE during the peak of the Northwest rotavirus season
      (January to March) and children with confirmed rotavirus infection demonstrated
      similar risk factors and receiver operating characteristic curves. CONCLUSION: We
      conclude that a focused rotavirus vaccination policy using readily identifiable
      potential high-risk groups would be unlikely to prevent most infant
      hospitalizations associated with rotavirus infection. However, the safety of
      rotavirus vaccine in low birth weight and premature infants must be established,
      because these children appear to be at greater risk for hospitalization with
      viral GE and rotavirus.

PMID- 9917484
TI  - Preschoolers with syphilis.
AB  - Syphilis in preschoolers is rarely described in current medical literature,
      despite the rise in syphilis in both the adult and the pediatric populations
      during the past decade. Since that time, 3 children between 3 and 4 years of age
      have been diagnosed with syphilis at the Children's Hospital of Philadelphia. The
      presentations and clinical manifestations of syphilis in these 3 children are
      described, and the difficulty in identifying the source of infection is
      discussed. The presentations of these children included nephrosis and secondary
      syphilis, the corymbiform and palmar rash of syphilis, and subtle signs of late
      congenital infection in an otherwise asymptomatic child. One child had documented
      congenital infection, 1 had probable congenital infection that went untreated,
      and 1 did not have appropriate neonatal testing documented. None of the children
      gave a verbal history of sexual abuse, although it is likely that all three cases
      resulted from sexual abuse. The evaluation of preschool children with syphilis is
      confounded by the interpretation of acquired infection in consideration of a
      history of possible or documented congenital disease. The assessment is
      complicated further by problems with recognition of clinical disease, the
      inability of young children to provide a history, prenatal and neonatal testing
      methods used, changes in treatment recommendations made during the past decade,
      and inadequate follow-up to document cure of congenitally infected infants. With
      the increase in syphilis seen in recent years, physicians are more likely to
      encounter preschoolers with syphilis. Our ability to document acquired infection,
      however, is hampered by the difficulties encountered in following recommended
      guidelines for evaluation and follow-up and by limitations in interviewing young
      victims of sexual abuse, which may impair our ability to protect children from
      additional harm. Understanding the pathophysiology and progression of this
      disease remains challenging even in this modern era.

PMID- 9917485
TI  - Low birth weight: race and maternal nativity--impact of community income.
AB  - BACKGROUND: The purpose of this article is to determine the effect of community
      income as a co-factor in the association of low birth weight, race, and maternal
      nativity in New York City. METHODS: New York City birth records, 1988 through
      1994, provided data on maternal and infant characteristics. There were 274 121
      white and 279 826 black mothers included in this study. Black mothers were
      classified as US-born (South and Northeast) and foreign-born (the Caribbean,
      South America, and Africa). Based on the 1990 US census income data, census
      tracts of the city were aggregated by tertile of per capita income as low-,
      middle-, and high-income communities. Incidence of low birth weight was estimated
      by race, maternal nativity in the city as a whole, and each income community.
      RESULTS: Overall, black women had a substantially higher risk of low birth weight
      infants (<2500 g) than did whites (13.1% vs 4.8%). Foreign-born black mothers had
      a birth weight advantage over US-born black mothers (10.0% vs 16.7%). After
      controlling for socioeconomic and medical characteristics, the risks of low birth
      weight for blacks compared with whites were 0.95 (95% confidence interval: 0. 87
      1.03) and 0.86 (0.69-1.02) for Caribbean- and African-born black mothers,
      respectively. Moreover, in low-income communities, compared with white mothers,
      the risks for Caribbean- and African-born black mothers were 0.88 (0.79-0.97) and
      0.77 (0.61-0.96), respectively. By contrast, US and South American-born black
      mothers had a consistently higher risk of low birth weight infants, regardless of
      community income level. CONCLUSION: Low birth weight was significantly less
      frequent among whites than among blacks. However, this overall finding masked
      substantial variation among blacks, determined by maternal nativity and the
      income level of the community in which they lived. In fact, Caribbean- and
      African-born black mothers had birth outcomes generally similar to and, in poor
      communities, even more favorable than those for whites.

PMID- 9917486
TI  - Prevalence, patterns, and correlates of voluntary flunitrazepam Use.
AB  - OBJECTIVE: To determine prevalence, patterns, and correlates of voluntary
      flunitrazepam use in a sample of sexually active adolescent and young adult women
      14 to 26 years of age. DESIGN: Cross-sectional survey. SETTING: University-based
      ambulatory reproductive health clinics. PATIENTS OR OTHER PARTICIPANTS: There
      were 904 women self-identified as white, African-American, or Mexican-American.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Lifetime, frequency, patterns, and
      physical effects of flunitrazepam use. RESULTS: Lifetime use was reported by 5.9%
      (n = 53) of subjects, with frequency of use ranging from 1 to 40 times.
      Flunitrazepam was taken most often with alcohol (74%), and 49% took this
      substance with other illicit drugs. Logistic regression analyses controlling for
      age and race/ethnicity found that users were significantly more likely than were
      nonusers to report lifetime use of marijuana (odds ratio [OR] = 3.6) or LSD (OR =
      5.2), having a peer or partner who used flunitrazepam (OR = 21.7), pressure to
      use flunitrazepam when out with friends (OR = 2.7), and a mother who had at least
      a high school education (OR = 2.6). Finally, 10% of voluntary users reported
      experiencing subsequent physical or sexual victimization. CONCLUSIONS: Voluntary
      use of flunitrazepam is becoming a health concern to sexually active young women
      who reside in the southwestern United States. Young women who have used LSD or
      marijuana in the past or who have a peer or partner who used this drug appear to
      be at the greatest risk.

PMID- 9917487
TI  - Formula tolerance in postbreastfed and exclusively formula-fed infants.
AB  - OBJECTIVE: Perceived intolerance to infant formula is a frequently reported
      reason for formula switching. Formula intolerance may be related to perceived
      symptoms of constipation, fussiness, abdominal cramps, and excessive spit-up or
      vomit. Commercially available formulas differ from each other in processing and
      in sources and levels of protein, lipids, and micronutrients. These differences
      may affect tolerance. The objective of this article was to compare the tolerance
      of two commercially available powder infant formulas that differ in composition.
      Measures of tolerance in exclusively breastfed infants weaned to an infant
      formula and exclusively formula-fed infants were evaluated. METHODS: Two clinical
      studies were conducted. In study 1, 82 healthy, full-term infants who were
      exclusively breastfed at the time of enrollment were randomized at weaning to
      formula A (commercially available Similac With Iron Powder) or formula B
      (previously available Enfamil With Iron Powder). Parents completed daily records
      of tolerance during exclusive breast milk feeding, during the weaning period, and
      for a 2-week exclusive formula-feeding period. In study 2, 87 healthy, full-term
      infants who were exclusively formula-fed at the time of study enrollment (by 2
      weeks of age) were fed a standard cow milk-based formula (previously commercially
      available Similac With Iron Powder) and then randomized to receive formula A or B
      for a 2-week period. Parents completed daily records of tolerance throughout the
      study. Formula A was a cow milk-based formula with a whey:casein ratio of 48:52
      and a fat blend of 42% high-oleic safflower, 30% coconut, and 28% soy oils.
      Formula B was a cow milk-based formula with a whey:casein ratio of 60:40 and a
      fat blend of 45% palm olein, 20% soy, 20% coconut, and 15% high-oleic sunflower
      oils. Both formulas had lactose as the source of carbohydrate and contained 12 mg
      of iron per liter. Only formula A contained nucleotides at the time of the study.
      Measures of tolerance included volume of each formula feeding, occurrences of
      spit-up and/or vomit, and the color (yellow, green, brown, or black) and
      consistency (water, loose/mushy, soft, formed, or hard) of each stool. RESULTS:
      In both studies, volume of formula intake, weight gain, and incidence of spit-up
      or vomit did not differ between feeding groups. In study 1, stool frequency
      decreased significantly from the exclusive breast milk period to weaning. Stools
      also became firmer as infants moved from breast milk to weaning and to exclusive
      formula feeding. When formula was introduced into the diet, stools became less
      yellow and more green. Infants weaned to formula B had less frequent stools,
      fewer brown stools, and more yellow stools than did infants fed formula A. In
      both studies, infants fed formula B experienced significantly firmer stools than
      did those fed formula A. CONCLUSIONS: The present clinical studies indicate that
      the composition and/or processing of milk-based powder iron-fortified infant
      formulas affect stool characteristics experienced by infants. The inclusion of
      palm olein oil in formula B may be the reason for the observed differences in
      stool characteristics. Palm olein is used in infant formulas to provide palmitic
      acid at a level similar to that found in breast milk. However, palmitic acid from
      palm olein is arranged differently from that in breast milk triglyceride and is
      poorly absorbed. Unabsorbed palmitic acid tends to react with calcium to form
      insoluble soaps, and the level of these soaps is correlated with stool hardness.
      The pattern of softer stools and greater frequency of stooling associated with
      formula A is similar to the stool pattern in the exclusively breastfed infant.
      Thus, the use of formula A may ease the transition from breast milk to formula
      feeding and ameliorate parents' perception that constipation is associated with
      iron-fortified formula.

PMID- 9917488
TI  - Teaching pediatric procedures: the Vancouver model for instructing Seldinger's
      technique of central venous access via the femoral vein.
AB  - The way in which physicians are trained to do invasive practical procedures is an
      ongoing challenge for educators. Percutaneous insertion of a central line via the
      femoral vein using the Seldinger technique is an important practical pediatric
      procedure, and the need for physicians to be educated in the necessary skills is
      recognized in current training initiatives such as Pediatric Advanced Life
      Support (PALS) and Advanced Pediatric Life Support. Unfortunately, the majority
      of instruction in central venous access techniques is theoretic. This approach
      does not provide the hands-on training needed to give practitioners the necessary
      practical experience, or confidence in their skills. Practice using simulated
      tissue can enable physicians to perform practical skills with greater confidence.
      However, although commercially available models exist for peripheral venous
      access, a recent cross-Canada survey of the 13 PALS program coordinators and a
      similar inquiry to the American Heart Association indicated that none of them had
      a pediatric practice model for central venous access. We describe 1) how to
      construct from materials readily available a pediatric model for the insertion of
      central venous catheters into the femoral vein using the Seldinger technique, and
      2) an evaluation of the change in confidence learning with the model engendered.
      In our experience, this model is inexpensive (less than $50) and can be
      replicated readily by others for use as a teaching aid. It provides inexperienced
      physicians the opportunity to learn the practical elements of the technique and
      acquire confidence in the Seldinger method. Our hypothesis was that the
      confidence and skill of physicians would be increased by practical experience of
      central line insertion using a realistic model. The model enables trainees to be
      taught the technique described in the PALS manual to locate the femoral artery.
      They then can learn to introduce a thin-walled needle or over-the-needle
      catheter, one finger's breadth below the inguinal ligament and just medial to the
      location of the femoral artery. The needle or over-the-needle catheter then can
      be advanced at the correct angle if the needle is directed toward the model's
      umbilicus. As occurs in vivo, the model allows for a free flow of fluid to be
      obtained as the "vessel" is entered. If the Foley catheter simulating the vessel
      is transfixed, negative pressure applied as the needle is withdrawn will result
      in fluid being obtained as the needle tip reenters the "vessel." The syringe then
      can be removed from the needle, and the key elements of the procedure-correct
      insertion of the Seldinger guide wire and passage of the venous catheter over the
      guide wire into the vessel-can be practiced. If desired, instruction also can be
      given on the use of a dilator and techniques of taping the catheter in place and
      all the appropriate techniques to avoid potential air embolism. However, the
      model does not lend itself to instruction in suturing. The model has been used to
      teach the practical elements of this technique to 428 physicians (emergency
      physicians, 49%; pediatricians, 24%; other physicians, 20%; pediatric residents,
      7%). Their success rate for cannula insertion in three or fewer attempts was 87%.
      The last 218 physicians were evaluated to assess the influence of learning with
      the model on their confidence to perform the technique successfully in an
      emergency. Before training they were asked, "Have you done a pediatric
      resuscitation course that taught this technique in theory?" and "Rate your
      confidence level for performing central vascular access in a patient from 0 to 5
      (none, very little, some, moderate, good, complete)." This rating was repeated
      after the training session using the model. For 154 (71%) answering "yes" to a
      previous resuscitation course, mean scores were 1.52 (standard error [SE] +/-
      0.91) after theoretic instruction and 4.06 (SE +/- 0.47) after practical
      education using our model. The 64 (29%) physicians

PMID- 9917489
TI  - Congenital hypothyroidism and nonimmune hydrops fetalis: associated?
AB  - Hydrops fetalis (HF) consists of an abnormal accumulation of fluid in two or more
      fetal compartments, including ascites, pleural effusion, pericardial effusion,
      and skin edema. Almost all observed cases of HF are of the nonimmune type, the
      causes of which remain undetermined in 15% of patients. We report a newborn
      infant with nonimmune hydrops fetalis (NIHF) and congenital hypothyroidism. The
      infant's mother was healthy and there were no malformations of the placenta or
      umbilical cord. The infant did not show any structural abnormalities of his
      central nervous, cardiovascular, gastrointestinal, or urinary tract systems, and
      there was no evidence of anemia, infectious disease, or inborn error of
      metabolism. An immune-based process was unlikely, because the blood group of the
      mother and infant was A-positive and results of an indirect Coombs test in the
      mother and a direct Coombs test in the infant were negative. The patient's
      condition gradually improved with mechanical ventilation, repeated
      thoracocentesis, and total parenteral nutrition. By day 5 of age the skin edema,
      pericardial effusion, and ascites disappeared, but accumulation of significant
      amounts of chylous pleural fluid persisted. Because of lethargy, FT4 and thyroid
      stimulating hormone levels were obtained and showed hypothyroidism. Thyroid
      hormone supplementation was then started, and within 4 days the infant became
      more vigorous and was weaned from mechanical ventilation. After 7 days, the
      chylothorax resolved completely as the serum thyroxine level normalized. No
      reaccumulation of pleural effusion was noticed. The infant started to gain weight
      and was discharged from the hospital at 35 days of age. A possible
      pathophysiologic association between congenital hypothyroidism and NIHF is
      discussed. NIHF may be caused by lymphatic congestion attributable to an
      impairment of lymphatic flow and a delayed return of lymph to the vascular
      compartment. There could be a possibility that because of thyroid hormone
      deficiency in this patient, there was reduced adrenergic stimulation of the
      lymphatic system. This could result in a sluggish flow of the lymph with
      engorgement of the lymphatic system, leakage of lymph into the pleura and the
      interstitial spaces, and the production of chylothorax with NIHF. Animal studies
      demonstrate a direct relationship between lymph flow rate or lung liquid
      clearance and adrenergic receptor activity in the lymphatic system. These
      observations support our hypothesis that deficient adrenergic activity in
      congenital hypothyroidism might lead to chylothorax with NIHF in the fetus. We
      speculate that thyroid hormone may play a role in the regulation of adrenergic
      receptors in the lymphatic system and lungs, thus modulating both the lymphatic
      flow rate and lung liquid clearance, and facilitating the resolution of
      chylothorax. Examination of thyroid functions should be included in the
      investigation of fetuses and neonates with NIHF of an obscure origin.

PMID- 9917490
TI  - Intractable diarrhea from cytomegalovirus enterocolitis in an immunocompetent
      infant.
AB  - Infection with cytomegalovirus (CMV) in infants can be congenital or perinatal.
      Infected infants may be asymptomatic or present with pneumonia, rash,
      hepatosplenomegaly, or encephalitis.1 In the presence of an immunodeficiency,
      severe and sometimes fatal disease may occur. To our knowledge, CMV has not been
      identified previously as a cause of intractable diarrhea of infancy. We report
      the case of a 5-week-old immunocompetent infant with intractable diarrhea
      attributable to CMV-induced enterocolitis. Recognition of this infection and
      initiation of ganciclovir therapy was associated with a rapid improvement and
      resolution of the diarrhea.

PMID- 9917491
TI  - Trends in diarrhea-associated hospitalizations among American Indian and Alaska
      native children, 1980-1995.
AB  - OBJECTIVE: To describe trends in diarrhea- associated hospitalizations among
      American Indian and Alaska Native (AI/AN) children and to estimate the morbidity
      from rotavirus. DESIGN: Retrospective analysis of Indian Health Service hospital
      discharge records. PATIENTS: AI/AN children 1 month through 4 years of age with a
      diarrhea-associated diagnosis listed on the hospital discharge record. SETTING:
      Hospitals on or near US Indian reservations from 1980 through 1995. RESULTS:
      During 1980 through 1995, 21 669 diarrhea-associated hospitalizations were
      reported among AI/AN children. The annual incidence of diarrhea-associated
      hospitalizations declined by 76% from 276 per 10 000 in 1980 to 65 per 10 000 in
      1995. The median length of hospital stay decreased from 4 days during 1980-1982
      to 2 days during 1993-1995. Diarrhea-associated hospitalizations peaked during
      the winter months (October through March), especially among children 4-35 months
      of age, with the peaks appearing first in the Southwest during October and moving
      to the East in March. In the early years of the study (1980-1982), the rate of
      diarrhea-associated hospitalizations among AI/AN children (236 per 10 000) was
      greater than the national rate (136 per 10 000). By the end of the study period
      (1993-1995), the rate for AI/AN children (71 per 10 000) was similar to the
      national rate (89 per 10 000), although the rate for AI/AN infants remained
      higher than the national rate for infants. CONCLUSIONS: Diarrhea-associated
      hospitalization rates for AI/AN children have declined to a level similar to that
      of the national population. Rotavirus may be an important contributor to
      diarrheal morbidity among AI/AN children, underscoring the need for vaccines
      against this pathogen.

PMID- 9917492
TI  - Transalar sphenoidal encephalocele and respiratory distress in a neonate: a case
      report.
AB  - We present a full-term newborn infant who suffered from immediate postpartum
      severe respiratory distress. The infant had an inspiratory stridor as a result of
      a swelling of the soft palate, extending from the roof of the nasopharynx.
      Transoral endotracheal intubation resulted in normal saturation levels.
      Histologic examination after an open biopsy showed mature neuroglial tissue.
      Radiology demonstrated the presence of a right parapharyngeal process obstructing
      the nasopharynx and oropharynx and extending to the right middle and posterior
      fossa, via the foramen ovale. After transoral debulking, the infant was extubated
      successfully. After an uneventful period of 5 months, the patient was readmitted
      at our hospital for treatment of meningitis. Subsequently, the inspiratory
      stridor recurred, and staged surgery was performed. First, a transcranial
      approach was used to remove a large intradural part of the process and close the
      defect at Meckel's cave. Two weeks later the retro- and parapharyngeal part of
      the process were removed transorally. Given the site of the defect of the skull
      base and the intradural location of the process, the diagnosis is a transalar
      sphenoidal encephalocele. This is a rare type of basal encephalocele, and has
      never been reported in an infant nor known to present with respiratory distress.
      The pathogenesis, clinical presentation, pathology, and therapeutic implications
      of basal encephaloceles are discussed.

PMID- 9917493
TI  - Long-term remission for disseminated Mycobacterium avium-intracellulare complex
      associated with antibody deficiency.
AB  - Mycobacterium avium-intracellulare (MAI) is a ubiquitous organism with limited
      virulence in the immunocompetent host. Disseminated disease is associated with a
      high mortality rate. Except for localized cervical adenitis, MAI disease is rare
      in immunocompetent children. We report a child with antibody deficiency
      (dysgammaglobulinemia) and disseminated MAI infection, in whom complete, long
      term remission was attained with multiple antimycobacterial therapy. The patient
      presented with progressive cervical lymphadenopathy and hepatomegaly at 7 years
      of age. A lymph node biopsy showed acid-fast bacilli and granulomas. Despite a
      transient response to conventional antituberculous therapy, including isoniazid
      and rifampin, his symptoms progressed. Cultures from blood, bone marrow, spleen,
      and cervical lymph node tissues revealed an MAI organism. Subsequent treatment
      using a combination of clarithromycin, amikacin, and ethambutol for 16 months
      resolved clinical symptoms, and subsequent blood culture results became negative.
      By the time of this report, the patient has been disease-free for 4 years.
      Multiple-drug therapy is promising for the treatment of MAI in children with
      antibody deficiency; however, the selection of antiinfective drugs should include
      a member of the newer macrolide family. acquired immunodeficiency syndrome,
      clarithromycin, dysgammaglobulinemia, Mycobacterium avium-intracellulare,
      treatment.

PMID- 9917494
TI  - Tumor stimulator cell modification by infection with Newcastle Disease Virus:
      analysis of effects and mechanism in MLTC-CML cultures.
AB  - Effects of tumor stimulator cell modification by infection with Newcastle Disease
      Virus (NDV) are described as analysed in vitro in mixed lymphocyte tumor cell
      cultures (MLTC). Direct antitumor effects were seen with human melanoma or colon
      carcinoma cells in a dose- and time-dependent manner when using live but not UV
      inactivated virus. When T cell stimulation was measured by [3H]-thymidine uptake,
      NDV infected tumor stimulator cells did not show an augmentation but rather an
      inhibitory effect in comparison to non-infected stimulator cells. Virus infected
      tumor stimulator cells were, however, capable of augmenting the induction of
      tumor specific cytotoxic T cells in MLTC-CML assays when using murine ESb
      lymphoma immune cells and syngeneic NDV modified ESb cells as stimulators. A CML
      stimulatory effect was also shown for NDV modified third party cells and thereof
      derived conditioned medium. These effects are most likely explained by interferon
      which is induced in tumor cells by NDV infection and by interferon-a which is
      induced in responder cells when stimulated with NDV infected stimulator cells.

PMID- 9917495
TI  - Differential expression of endogenous galectin-1 and galectin-3 in human prostate
      cancer cell lines and effects of overexpressing galectin-1 on cell phenotype.
AB  - We have analyzed the expression of galectin-1 and galectin-3 in four human
      prostate carcinoma cell lines. Northern analysis and immunoblotting experiments
      showed that three cell lines express both galectins. However, only galectin-1 was
      detected on the surface of these cells. The LNCaP line expressed neither
      galectin. LNCaP was transfected with galectin-1 and four clones were isolated,
      all of which expressed galectin-1 on the cell surface. Kinetics of binding to
      extracellular matrix proteins appeared to be accelerated in the transfected
      lines, but overall binding was not enhanced. When the same experiments were
      performed in the presence of EDTA to eliminate the effects of integrins, binding
      of a galectin-1 clone to laminin and fibronectin was increased relative to the
      control cell line. We propose that galectins may contribute to the adhesive
      properties of some prostate cancer cells.

PMID- 9917497
TI  - Effects of development of host immunity on the biodistribution of xenogeneic MHC
      non-restricted cytotoxic T cells: implications for adoptive cell therapy of
      cancer.
AB  - The human MHC non-restricted cytotoxic T cell line TALL-104 has potent anti-tumor
      effects in dogs with spontaneous tumors. This study was designed to examine the
      effects of the development of host immune responses on the baseline organ
      distribution of TALL-104 cells in healthy dogs. 111In-oxine labeled TALL-104
      cells (107 cells/kg) were infused systemically in three dogs, either on day 1, 3,
      or 5 of a 5-day injection cycle; two dogs received two more injections of the
      labeled cells at monthly intervals, whereas the third dog received free 111In
      oxine, 3 months after the first 5-day infusion. Analysis of blood and plasma cell
      clearances and imaging studies indicated a progressively faster clearance of the
      cells from the blood and organs after multiple daily injections as well as at the
      time of each monthly boost when host immune responses against the xenogeneic
      cells had developed. These findings have important therapeutic implications for
      the design of effective TALL-104 cell administration schedules in clinical
      trials.

PMID- 9917496
TI  - Induction of differentiation and apoptosis in the prostate cancer cell line LNCaP
      by sodium butyrate and galectin-1.
AB  - Galectin-1 has been implicated in the process of vertebrate developmental
      regulation. Sodium butyrate is an established differentiation-inducing agent and
      has been shown to increase galectin-1 expression in colon carcinoma cells. We
      studied the roles of butyrate and galectin-1 in the induction of differentiation
      and apoptosis in the prostate cancer cell line LNCaP. Treatment of LNCaP cells
      with butyrate resulted in induction of galectin-1 expression in a time- and dose
      dependent manner. Treatment with butyrate also resulted in inhibition of
      proliferation, morphologic changes consistent with a differentiated phenotype,
      and induction of apoptosis. Prostate specific antigen expression was transiently
      reduced. To determine which of these effects might be secondary to the induction
      of galectin-1, LNCaP cells were transfected with a galectin-1 expression vector.
      The transfected cells displayed growth inhibition and an increased rate of
      apoptosis. PSA expression was not affected. We conclude that galectin-1 may be
      responsible for many of the phenotypic changes resulting from butyrate treatment
      and may function downstream in the pathway of butyrate-induced differentiation.
      We also found PSA to be somewhat inconsistent as an indicator of differentiation
      of LNCaP cells, likely due to other factors influencing its expression.

PMID- 9917498
TI  - Biodistribution of human MHC non-restricted TALL-104 killer cells in healthy and
      tumor bearing mice.
AB  - The human cytotoxic T cell line TALL-104 displays potent anti-tumor effects in
      animals with spontaneous and induced malignancies. We investigated the
      biodistribution of TALL-104 cells in tumor bearing and healthy mice. 111In
      labeled TALL-104 cells, injected intravenously, localized primarily in the lungs
      for the first 2 h, and redistributed to liver, spleen, and kidneys in the
      following 24 h both in immunodeficient and immunocompetent mice. TALL-104 cells
      consistently accumulated in the tumor and at sites of metastases. In animals
      injected with free 111In-oxine, most of the radioactivity remained in the blood
      pool with no significant organ accumulation. These data support the tumor homing
      properties of TALL-104 cells, information which is crucial to their therapeutic
      efficacy in forthcoming clinical trials.

PMID- 9917499
TI  - Killing effects of 5-fluorouracil on human biliary tract cancer cell lines.
AB  - Data concerning the cellular sensitivity of human biliary tract cancer cell lines
      to 5-FU are scarce. The purpose of the present study was to evaluate the cellular
      sensitivity of Mz-ChA-2 (derived from gall bladder cancer) and SK-ChA-1 (derived
      from bile duct cancer) to 5-FU. The clonogenic capacity of these lines after
      pulse (1 h) or continuous (168 h) administration of various 5-FU concentrations
      (0.1-100 microg/ml) was evaluated in exponentially growing cells as well as in
      those that had reached the plateau phase. In both cell lines, exponentially
      growing cells were 1.8-times more susceptible to 5-FU than those in plateau
      phase. However, when cells in the same growth phase were compared, Mz-ChA-2 cells
      were 10 times more sensitive to the drug than SK-ChA-1 cells. Regardless of the
      growth phase or cell line, increasing the duration of exposure to 5-FU decreased
      the proportion of surviving cells. Even at a non-cytocidal dosage, exposing the
      cells for three doubling times markedly decreased the number of viable cells
      remaining after treatment.

PMID- 9917500
TI  - A novel aromatase inhibitor, vorozole, shows antitumor activity and a decrease of
      tissue insulin-like growth factor-I level in 7, 12-dimethylbenz[a]anthracene
      induced rat mammary tumors.
AB  - Effects of vorozole, a potent and specific non-steroidal aromatase inhibitor,
      were evaluated on female Sprague-Dawley (SD) rats with 7, 12
      dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Vorozole at a dose of
      0.25, 1.0 and 4.0 mg/kg was orally administered once a day for 28 consecutive
      days. A significant regression in tumor size was observed in each treated group
      at 1, 2, 3 and 4 weeks after the start of treatment compared with control group.
      Tissue insulin-like growth factor I (IGF-I) in the DMBA-induced tumors in each
      treated group significantly decreased in a dose-dependent fashion compared with
      control group. These results show the mechanism of vorozole in DMBA-induced rat
      mammary tumors.

PMID- 9917501
TI  - Evaluation of curability and prediction of prognosis after surgical treatment for
      hepatocellular carcinoma by lens culinaris agglutinin-reactive alpha-fetoprotein.
AB  - The clinical significance of serum lens culinaris agglutinin-reactive alpha
      fetoprotein (AFP-L3), which can distinguish between hepatocellular carcinoma and
      hepatitis by detecting a sugar chain micro heterogeneity, was evaluated for its
      possible ability to recognize previously undetectable residual tumors, and for
      increasing the accuracy of prognosis after surgical treatment for hepatocellular
      carcinoma. Serum lens culinaris agglutinin-reactive alpha-fetoprotein was
      measured pre- and post-operatively in 130 patients who underwent curative
      surgical treatment for hepatocellular carcinoma. The preoperative AFP-L3 positive
      rate was 35.4%. AFP-L3 remained positive postoperatively in 28 of the 46
      preoperative AFP-L3 positive patients, and converted to positive in 4 of the 84
      preoperative AFP-L3 negative patients. Regardless to preoperative AFP-L3, the
      postoperative AFP-L3 positive patients had a poorer recurrence-free rate
      (p<0.0001). The postoperative L3 positive patients had a high incidence of
      recurrence due to metastasis, but did not have recurrence due to multicentric
      origin. Multivariate analysis revealed that AFP-L3 (p<0.0001) was the most
      independently significant factor for predicting survival after surgery among
      several conventional prognostic factors. Thus, AFP-L3 is a valuable marker for
      evaluation of curability of surgical treatment and for improving the accuracy of
      prognosis.

PMID- 9917502
TI  - A multidrug-resistant breast cancer cell line induced by weekly exposure to
      doxorubicin.
AB  - Attempts to study drug resistance in vitro have focused on continuous exposure of
      cell lines to cytotoxic agents that results in marked resistance. In an effort to
      examine drug resistance in an environment that is more typical of a clinical
      setting, monolayered human breast cancer cells (MCF-7) were exposed weekly for
      one hour to doxorubicin at a concentration that is achieved in vivo (0.1
      microg/ml). After 20 weeks, the treated cell line (C20) was found to be resistant
      to doxorubicin by a factor of 2.0-2.5 at the 10 and 1% cell survival level
      compared to parent MCF-7 cells. Additionally, cross resistance to other
      chemotherapeutic agents including etoposide, vincristine, cisplatin, and
      mitomycin C was observed. Similar to other models of in vitro drug resistance, no
      modification of radiosensitivity was observed in C20 cells. The p170 glycoprotein
      was not overexpressed on C20 cells as assessed by the anti-p170 glycoprotein
      monoclonal antibody C219 staining nor was mRNA for the mdr-1 or MRP gene
      overexpressed. In addition, the mdr-blocking agent verapamil had no effect on the
      level of resistance encountered in tissue culture. C20 cells did not differ from
      the parent cell line with respect to cell cycle distribution, doubling time, GSH,
      GSH peroxidase, GSH reductase or GSH transferase levels. After a one-hour
      exposure to doxorubicin, lower intracellular doxorubicin levels were found in C20
      cells compared to the parent line which provides at least a partial explanation
      for resistance, although the mechanism for this is unclear. Although the
      magnitude of resistance observed in the C20 cell line is low compared to other in
      vitro models of drug resistance, the modest level of drug resistance is probably
      sufficient to explain drug resistance seen clinically. The model of non-mdr
      mediated drug resistance presented may be a more relevant model for the
      evaluation of drug resistance in vitro.

PMID- 9917503
TI  - Clinicopathologic significance of protein induced vitamin K absence or antagonist
      II and alpha-fetoprotein in hepatocellular carcinoma.
AB  - Protein induced vitamin K absence or antagonist II (PIVKA-II) and alpha
      fetoprotein (AFP) have been considered useful serum markers of hepatocellular
      carcinoma (HCC). In this study, we examined the clinicopathologic significance of
      these tumour markers in patients with HCCs by measuring their serum levels and
      performing immunohistochemistry. We studied 349 Japanese patients with HCCs.
      Their serum PIVKA-II and AFP levels were determined by enzyme immunoassay before
      treatment. We examined the correlations between serum PIVKA-II and AFP levels and
      tumour size, presence of satellite nodules, histologic HCC grade, and concomitant
      liver diseases and subjected tumour tissues to immunohistochemical staining to
      detect PIVKA-II and AFP expression. The serum PIVKA-II levels of patients with
      poorly differentiated HCCs were significantly higher than those of patients with
      well and moderately differentiated HCCs (p<0.05) and they were higher in HCC
      patients with than without satellite nodules. The serum AFP levels were
      influenced significantly by concomitant liver diseases, but not by the other
      factors. Immunohistochemical staining revealed the PIVKA-II expression levels of
      poorly differentiated HCCs were higher than those of well and moderately
      differentiated HCCs (p<0.05). Some HCC cells were PIVKA-II-positive, others were
      AFP-positive, and some expressed both. The serum PIVKA-II concentration was a
      better indicator of HCC than AFP, as it was not influenced by concomitant liver
      diseases. The presence of PIVKA-II in serum correlated with the presence of
      satellite nodules and the histologic HCC grade, a result concordant with the
      immunohistochemical findings.

PMID- 9917504
TI  - Big but weak: how many pathogenic genes does human herpesvirus-8 need to cause
      Kaposi's sarcoma? (Review).
AB  - Human herpesvirus-8 (HHV-8) is implicated in the pathogenesis of Kaposi's sarcoma
      (KS). In the last two years several HHV-8 gene products were heralded to 'cause
      KS' without any evidence that the respective gene is expressed in the tumor cells
      of KS lesions. In this framework it is of interest that almost 10% of the genes
      encoded by HHV-8 have been suggested to promote KS development due to either
      mitogenic, anti-apoptotic, chemoattractive, angiogenic or transforming
      activities. The rapidly growing number of HHV-8-encoded genes with 'KS causing'
      activities raises the question of why HHV-8 may need so many genes to trigger
      growth of KS that appears to be more closely related to a hyperplasia than to a
      real sarcoma. In this review an overview of the current knowledge of HHV-8 gene
      expressions in KS lesions in vivo is presented.

PMID- 9917505
TI  - Transcriptional regulation of MMP-9 expression in stromal cells of human giant
      cell tumor of bone by tumor necrosis factor-alpha.
AB  - We determined whether certain factor(s) secreted by multinucleated giant cells,
      which is of monocyte/macrophage lineage in giant cell tumor of bone (GCT),
      regulate the induction of matrix metalloproteinase (MMP)-9 expression in
      mononucleated stromal cells. Our data derived using enzyme linked immunosorbant
      assays (ELISAs) suggest that the GCT cells in primary culture produce both MMP-9
      and tumor necrosis factor-alpha (TNF-alpha). Further, the MMP-9 expression in GCT
      primary cultures was partially abrogated by neutralizing antibody to TNF-alpha,
      suggesting that TNF-alpha secretion by the multinucleated giant cells may be one
      of the factors responsible for the production of MMP-9 by the stromal cells in
      vivo. In order to confirm this we examined the role of TNF-alpha on the induction
      of MMP-9 expression in bone GCT stromal cells. These cells express MMP-2, but not
      MMP-9. However, treatment of these cells with TNF-alpha induced the expression of
      MMP-9 in a concentration-dependent manner. Kinetic experiments revealed that the
      secretion of MMP-9 peaked 12 h post TNF-alpha stimulation. Immunofluorescence
      studies confirmed the expression of MMP-9 after stimulation of GCT stromal cells
      with TNF-alpha. Further, TNF-alpha-induced MMP-9 expression was completely
      blocked with neutralizing antibody to TNF-alpha, thereby demonstrating the
      specificity. In addition, the induction of MMP-9 expression by TNF-alpha was
      completely abrogated in the presence of cycloheximide, a protein synthesis
      inhibitor, suggesting that de novo protein synthesis may be required. Nuclear run
      on analysis demonstrated that treatment of GCT stromal cells significantly
      enhanced the MMP-9 gene transcription. Together, our data suggest that TNF-alpha
      secreted by the multinucleated giant cells up-regulates MMP-9 expression in GCT
      stromal cells by the induction of certain transcription factors, which in turn
      enhanced the rate of transcription of MMP-9 gene. These studies also suggest the
      existence of an essential cell-cell interaction in the regulation of MMP-9
      expression in GCT.

PMID- 9917507
TI  - Interphase cytogenetic diagnosis of bladder cancer on cells from urine and
      bladder washing.
AB  - In order to determine the value of fluorescence in situ hybridization (FISH) in
      the diagnosis and follow-up of bladder cancer interphase cytogenetics was
      performed on cells from urine and bladder washings. 50 ml of urine or bladder
      washings were collected. FISH was carried out using centromere probes for
      chromosomes 7, 8, 9 and 12 according to standard protocols. In each case 100 cell
      nuclei were analysed. Fifty-four samples from urine and 67 samples from bladder
      washing were analysed by FISH in comparison with results obtained by conventional
      cytology. Sensitivity of detection of tumor cells by FISH was 68.5% in urine and
      63% in bladder washings regardless of tumor stage and grade. Sensitivity obtained
      by conventional cytology was 50% in urine and 77.3% in bladder washings. FISH on
      cells from urine samples is an effective complement to the standard urine
      cytology. Using centromere probes this approach is characterized by high
      specificity and sensitivity in tumors with T-category higher than pTa and grade
      higher than G1.

PMID- 9917506
TI  - Relationship between P-glycoprotein expression and p53 status in high-grade
      osteosarcoma.
AB  - The transcription of MDR1 gene may be increased by mutation or loss of function
      of p53 gene. In this study, we investigated whether in osteosarcoma, the p53
      status is correlated with overexpression of the MDR1 gene product P-glycoprotein.
      The relationship between P-glycoprotein expression and p53 status was analyzed by
      immunohistochemistry in 64 primary and 11 metastatic high-grade osteosarcomas. In
      the same series, we also assessed the nuclear accumulation of MDM2 protein, whose
      binding to p53 protein provides an alternative mechanism of p53 inactivation. No
      association was found between mutant-p53 and MDM2 nuclear accumulation either
      with P-glycoprotein expression or with clinical course. Only increased expression
      of P-glycoprotein in tumor cells was significantly associated with a poor
      outcome, further supporting the adverse prognostic value of this marker in
      osteosarcoma.

PMID- 9917508
TI  - Characterization of purified cathepsin D from malignant human breast tissue.
AB  - The aspartyl protease cathepsin D (EC 3.4.23.5) appears to be found in increased
      amounts and/or abnormally secreted in breast cancer cells, and may contribute to
      the metastatic spread of malignancy. In the present study, cathepsin D was
      purified 4800-fold in 20% yield from malignant human breast tissue using affinity
      chromatography on pepstatin-agarose and DEAE-Sephadex chromatography. Slab gel
      SDS-PAGE of the purified cathepsin D indicated the presence of three major
      protein bands (31, 13, 12, kDa) and two minor protein bands (47, 29 kDa). Western
      blotting indicated that the 31 kDa band was the major immunoreactive species.
      Isoelectric focusing indicated that the purified cathepsin D consisted of three
      major isoforms at approximate pIs of 7.4, 7.0 and 6.6, and a possible isoform of
      lower activity centered around pI 3.2. The pH curve of purified cathepsin D
      indicated a broad optimum centered around pH 3.4. Lectin blotting suggested the
      presence of mannose residues but no evidence was found for lectin-available
      sialic acid, fucose, N-acetylglucosamine and galactose residues. The investigated
      properties of purified cathepsin D from malignant breast tissue are very similar,
      if not identical, to the properties of cathepsin D previously purified from
      normal human breast tissue. Our findings suggest that the elevated activity and
      antigenic levels of cathepsin D in malignant breast tissue are due to increased
      amounts of apparently normal enzyme.

PMID- 9917509
TI  - Antitumor effect of electrochemotherapy on colorectal carcinoma in an orthotopic
      mouse model.
AB  - Electropermeabilization was shown to markedly increase the sensitivity of murine
      colorectal carcinoma (CRC) cells to bleomycin (BLM), resulting in more than 2,500
      fold higher susceptibility to BLM. Subsequent in vivo electrochemotherapy with
      BLM revealed profound antitumor effects on subcutaneous CRC tumors. Furthermore,
      when electrochemotherapy with BLM was employed for the treatment of orthotopic
      CRC tumors in mice, significantly prolonged survival priods were observed. These
      results indicate the feasibility of electrochemotherapy with BLM for the
      treatment of CRC and demonstrate that electrochemotherapy can be translated from
      the treatment of cutaneous and subcutaneous tumors to the treatment of internal
      cancers including CRC.

PMID- 9917510
TI  - A high throughput system for the evaluation of protein kinase C inhibitors based
      on Elk1 transcriptional activation in human astrocytoma cells.
AB  - Protein kinase C (PKC) designates a family of kinases that regulate many
      essential functions including cell growth and differentiation. The tight
      regulation of PKC activity is crucial for maintaining normal cellular
      proliferation and excessive activity leads to abnormal or uncontrolled cell
      growth. Recent reports indicate that malignant glioma cell lines express 100 to
      1000-fold higher PKC activity when compared to non-neoplastic astrocytes. This
      high activity correlates well with the proliferation of tumor cells in vitro. We
      recently reported on the anti-proliferative properties of selective PKC
      inhibitors on the growth of U-373MG human astrocytoma cell line, and their
      ability to block mitogen-activated protein (MAP) kinase pathway activated by
      substance P (SP) neuropeptide receptor signaling via a PKC-dependent mechanism.
      Therefore, inhibiting PKC activity by selective PKC inhibitors may present a
      promising approach for improving astroglial brain tumor therapy. For this
      purpose, we constructed a high throughput model cell system to evaluate the
      efficacy of PKC inhibitors. This system is based on the measurement of light
      production in U-373MG cells stably transfected with the luciferase reporter gene
      whose expression depends on the transcriptional activation of GAL4-Elk1 fusion
      protein by enzyme components of the MAP kinase pathway and the upstream
      activation of PKC (PKC activation-->MAP kinases-->GAL4-Elk1 phosphorylation-
      >luciferase expression-->luciferase activity). In brief, we have demonstrated
      that the PKC activator 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced
      luciferase activity in this cell system is mediated via the MAP kinase pathway
      and can be blocked in the presence of MEK1 selective inhibitors (PD 098059 or
      U0126). We also demonstrated that TPA-induced luciferase activity in U-373MG
      stable clones can be blocked by PKC inhibitors (CGP 41251, Go 6976, and GF
      109203X) in a concentration dependent manner. In contrast, epidermal growth
      factor (EGF)-induced luciferase activity, which is independent of PKC activation
      (Ras-->Raf-1-->MEK1-->MAP kinases-->GAL4-Elk1 phosphorylation-->luciferase
      expression-->luciferase activity) can only be blocked using a selective EGF
      receptor inhibitor (AG 1478). In conclusion, we have constructed a model cell
      system for the high throughput screening and identification of PKC inhibitors
      potentially active against astrocytoma cells in culture.

PMID- 9917511
TI  - Suppression of tumorigenicity of rat liver epithelial tumor cell lines by a
      putative human 11p11.2-p12 liver tumor suppressor locus.
AB  - We have previously identified and mapped a locus within human chromosome 11p11.2
      p12 that suppresses the tumorigenic potential of a rat liver tumor cell line
      (termed GN6TF) which contains well defined chromosomal aberrations involving rat
      chromosomes 1, 4, 7, and 10. In the present study, we investigated the potential
      of this human 11p11.2-p12 liver tumor suppressor locus to suppress the
      tumorigenic potential of two other rat liver tumor cell lines (GN3TG and GP10TA)
      following microcell-mediated introduction of human chromosome 11. These tumor
      cell lines are aneuploid and contain chromosomal abnormalities that are similar
      to the GN6TF tumor line. The tumorigenic potential and other phenotypic
      characteristics of GN3TG-11neo and GP10TA-11neo microcell hybrid (MCH) cell lines
      were variable, and dependent upon the status of the introduced human chromosome
      11. MCH cell lines that retained the region of 11p11. 2-p12 delineated by
      microsatellite markers D11S1385 and D11S903 exhibited suppression of
      tumorigenicity in vivo (decrease in tumorigenicity and/or elongation of latency),
      whereas, the tumorigenic potential of one MCH line that lacked markers in this
      region of human 11p11.2-p12, but retained flanking markers, was not changed from
      that of the parental tumor cell line. The chromosomal interval between
      microsatellite markers D11S1385 and D11S903 encompasses the previously localized
      minimal liver tumor suppressor region, suggesting that a common locus is
      responsible for tumor suppression among the rat liver tumor cell lines examined.
      The results of the present study have verified the presence of a liver tumor
      suppressor locus within human 11p11.2-p12, and have identified a substantial
      number of microsatellite markers that are closely linked to this tumor suppressor
      region. These chromosomal markers will facilitate positional cloning of candidate
      genes from this region, and may prove useful for determining the involvement of
      this locus in the pathogenesis of human liver cancer.

PMID- 9917512
TI  - Adjuvant chemotherapy and radiation therapy for elimination of residual
      microscopic non-small cell lung cancer.
AB  - This study determined if patients with residual microscopic non-small cell lung
      cancer (NSCLC) following lung resection treated with combination chemotherapy and
      radiation realize prolonged survival. Ten men with microscopic NSCLC following
      resection were given chemotherapy and radiation therapy. Four (40%) of the ten
      patients were disease-free at 45 months and fully functional. Only two (20%) of
      the patients died of recurrent lung cancer. Of patients who died of lung cancer,
      recurrence occurred within five months of treatment and death occurred within one
      year. The findings suggest combination chemotherapy and radiation therapy delay
      or prevent recurrence from residual microscopic NSCLC following lung resection.

PMID- 9917514
TI  - Irreversible cancer cell-induced functional anergy and apoptosis in resting and
      activated NK cells.
AB  - The interaction of natural killer (NK) cells with target cells, such as K562,
      results in NK functional inactivation and apoptosis. The role of NK-activating
      cytokines, IL-2, IL-12, and IL-15, in the regulation of NK inactivation and
      programmed cell death by target cells was examined. Purified natural killer cells
      were obtained from human peripheral blood and either co-incubated with K562
      target cells and cytokines or the NK cells were pretreated with cytokines for 18
      h prior to co-culture with K562 cells. Sorted NK cells were examined for
      cytotoxic activity and NK co-cultured with K562 were examined for cytokine
      secretion, phenotyping and DNA fragmentation. The cytotoxic activity was
      inhibited and was not alleviated by cytokine treatment. Whereas the cytokine
      treatment maintained NK cell viability for several days, NK cell viability was
      decreased significantly in the presence of K562 target cells. Downregulation of
      CD16 and upregulation of CD69 on NK cells were induced by K562 target cells and
      no modulation of these antigens was observed with cytokine treatment. A
      subpopulation of target-treated NK cells succumbed to cell death by apoptosis and
      cell death was not rescued by the activating cytokines. These findings
      demonstrate that target-induced functional inactivation and apoptosis of NK cells
      were not rescued by the activating cytokines IL-2, IL-12, and IL-15 regardless of
      whether the NK cells were pretreated with cytokines prior to exposure to K562 or
      the cytokines were added to the NK-K562 mixtures. These results also suggest that
      signals triggered by the target cells and resulting in NK cell anergy and
      apoptosis override cytokine-mediated signals for activation, cell proliferation,
      and survival.

PMID- 9917513
TI  - Vascular endothelial growth factor/vascular permeability factor mRNA expression
      in patients with chronic hepatitis C and hepatocellular carcinoma.
AB  - Angiogenic factors such as vascular endothelial growth factor (VEGF) may be
      involved in neovascularization of malignant tumors. Our aim was to determine
      whether there is an increased VEGF mRNA expression in liver from patients with
      HCC and premalignant hepatitis C virus (HCV) with differing severity of
      inflammation. VEGF mRNA (VEGF165, VEGF189) was detected by reverse transcription
      and semi-quantitative polymerase chain reaction (RT-PCR) amplification in all
      liver samples. There was no difference in VEGF mRNA expression ratios (corrected
      for glyceraldehyde-3-phosphate dehydrogenase) among three groups:
      steatohepatitis, as a non-malignant non-viral control, 1. 05+/-0.35, n=8; chronic
      hepatitis C, 0.86+/-0.27, n=18; hepatocellular carcinoma, 1.06+/-0.43, n=10. VEGF
      mRNA expression was independent of the severity of HCV inflammation estimated by
      the histological activity index: low HAI (</=4, n=8) vs. high HAI (>/=10, n=10),
      0.93+/-0.31 vs. 0.81+/-0.24, p=ns. There was no significant difference in mean
      VEGF expression between HCC tumor (1.06+/- 0.43) and adjacent tissue (0. 85+/
      0.42) although the tumors tended to have higher expression than adjacent non
      malignant tissues. In conclusion, all liver samples of steatohepatitis, chronic
      HCV infection and HCC expressed VEGF mRNA, VEGF mRNA may be uniformly expressed
      in liver tissue, the level of expression is probably not related to virus
      infection or the severity of inflammation. Other angiogenic or angiostatic
      factors might be more involved in angiogenesis in HCC.

PMID- 9917515
TI  - Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma
      and their association with metastasis.
AB  - Prostate carcinoma (PC) is the second leading cause of cancer death in men in the
      western world. Although the role of oncogenes and growth factors in prostate
      carcinoma is still unclear, overexpression of the epidermal growth factor
      receptor (erbB-1) and the proto-oncogene erbB-2 have been reported in prostate
      tumors, and erbB-2 related to poor prognosis and distant metastasis. Recent
      allelotyping studies in prostate cancer have shown chromosomal gains in 7p and
      17q, regions where erbB-1 and erbB-2 are localized respectively, although no
      direct evidence of an increased gene copy number of either erbB-1 or erbB-2 has
      been reported. To address this question, we analyzed 20 benign prostatic
      hyperplasia (BPH) samples and 36 samples of metastatic and non-metastatic PC by
      means of semiquantitative PCR. Thus, 64% (11/17) and 52% (10/19) of metastatic
      and non-metastatic tumors respectively showed gains of the relative genomic
      content of erbB-1 and an association of erbB-1 with prostate cancer but not with
      metastasis. Additionally, 41% (7/17) of metastatic samples showed gains of erbB-2
      genomic content, suggesting an association of erbB-2 with metastasis and poor
      prognosis (p<0.005). No gains of erbB-1 or erbB-2 genomic content were detected
      in the BPH samples.

PMID- 9917516
TI  - Human neuroblastoma cell growth in tissue culture is regulated by opioid growth
      factor.
AB  - Human neuroblastoma is one of the most common solid tumors in infants and
      children and represents about 10% of all childhood cancers. Nearly 70% of the
      patients present with disseminated disease and the long-term prognosis remains
      poor for this group despite advances in diagnosis and therapy. In this study, we
      discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the
      growth of human neuroblastoma SK-N-SH in vitro; in view of this pentapeptide's
      action it has been termed opioid growth factor (OGF). OGF was found to be
      constitutively expressed and tonically capable of suppressing cell replication,
      and its effects were opioid receptor mediated. Growth inhibition was dose
      related, reversible, not cytotoxic, and independent of serum. Immunocytochemical
      studies detected both OGF and its related receptor, zeta, in the cytoplasm of log
      phase cells. Pharmacological binding assays revealed specific and saturable
      binding with a one-site model of kinetics; this high-affinity opioid receptor was
      identified as zeta. These data suggest that a native opioid peptide, OGF,
      interacts with a novel opioid receptor, zeta, to arrest the growth of human
      neuroblastoma.

PMID- 9917517
TI  - Small cell carcinoma of the uterine cervix: a clinicopathological review.
AB  - Small cell carcinoma of the cervix is rare, with an aggressive natural history.
      We report on a series of 11 patients treated at the Christie Hospital, Manchester
      and examine their treatment and survival. Eleven patients with small cell
      carcinoma of the cervix were identified retrospectively from patient case notes.
      Treatment was individualised and included a variety of combinations of surgery
      radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108
      months (crude disease-free survival 36%). They presented with earlier disease and
      were older than the average for the group. They were all initially treated with
      radical radiotherapy. 7 patients died between 7 and 25 months. Despite
      combination chemotherapy, survival with advanced disease was poor. Published
      studies are small and fail to provide definitive answers on the best management
      of small cell carcinoma of the cervix. Drawing on the experience of small cell
      carcinoma of the lung however, combination therapy with radiotherapy,
      chemotherapy and possibly surgery requires careful assessment by an oncologist.

PMID- 9917518
TI  - Heterotrimeric G proteins as fluoride targets in bone (review).
AB  - Fluoride is an acknowledged bone anabolic agent. Nevertheless, a narrow
      therapeutic window and the adverse effects at higher therapeutic doses prevent
      broad clinical application of fluoride for treatment of diseases of bone loss,
      such as osteoporosis. The cellular and molecular mechanisms of fluoride action
      are poorly understood. recent advances in the elucidation of signal transduction
      pathways induced by fluoride in osteoblastic cells are reviewed. Fluoride and
      traces of aluminum form a complex, fluoroaluminate, which stimulates cellular
      heterotrimeric G proteins. Such complex can form in food, drinking water and in
      the organism after administration of sodium fluoride. Fluoroaluminate crosses the
      cell membrane and directly binds to the membrane-associated inactive G alpha
      protein subunits. Within the G alpha subunit, fluoroaluminate occupies the
      position next to GDP. The resulting G alpha-GDP-AlF4- complex assumes an active
      state conformation, which resembles that of G alpha-GTP complex. Under
      physiological conditions, G alpha-GTP complex is formed upon activation of seven
      transmembrane receptors that couple to heterotrimeric G proteins. Both
      fluoroaluminate-activated and receptor-activated G alpha subunits are capable of
      transmitting intracellular signals that lead to cellular responses. In bone
      forming cells osteoblasts, fluoroaluminate stimulates pertussis toxin-sensitive G
      alpha i proteins. G alpha i activation leads to the reduction in cAMP (cyclic
      adenosine monophosphate) levels and to the activation of mitogen activated
      protein kinases, Erks (extracellular signal-regulated kinases) and p70 S6 kinase.
      These kinases are involved in the regulation of gene transcription and protein
      syntheses. Fluoroaluminate also stimulates pertussis toxin-insensitive proteins.
      Pertussis toxin-insensitive G proteins, most likely from G alpha 12 class, cause
      the activation of several cytoplasmic protein tyrosine kinases [Src, Pyk2
      (proline-rich tyrosine kinase 2), and Fak (focal adhesion kinase)]. Activation of
      Erks can lead to osteoblast proliferation and differentiation, while activation
      of Src, Pyk2 and Fak can modulate the adhesion properties of osteoblasts.
      Osteoblast adhesion may, in turn, influence differentiation, migration, and
      apoptosis of these cells. The susceptibility of osteoblasts to fluoroaluminate
      can be achieved by their specific cellular context and by the rigidity of the
      surrounding bone tissue. In particular, higher levels of G alpha i proteins and
      of certain focal adhesion proteins are expressed by osteoblastic rather than by
      fibroblastic cells. The rigidity of adhesion substratum of osteoblasts may signal
      on its own and potentiate the signaling by fluoroaluminate. The information on
      mechanisms of intracellular signaling by fluoroaluminate can be utilized to
      identify a fluoroaluminate mimic, a drug that exhibits anabolic action on bone
      with a broader therapeutic range and less adverse effects than fluoride.

PMID- 9917519
TI  - The involvement of proteasome in myogenic differentiation of murine myocytes and
      human rhabdomyosarcoma cells.
AB  - The murine C2C12 myocytes terminally differentiate to myotubes in the mitogen
      depletion, and a portion of the cells undergo apoptosis. In this study, a
      specific proteasome inhibitor lactacystin induced cell cycle withdrawal and
      precocious expression of myosin in C2C12 cells in mitogen-enriched medium, but
      these cells did not fuse to form myotubes. Mitogen-starved myocytes could not
      differentiate to myotubes under the proteasome inhibition. The genes for p21,
      MyoD, Myogenin and RB were activated, and p27 gene was repressed under the
      proteasome inhibition, suggesting the transcriptional regulation of these genes
      linked to the proteasome activity. The induction of p21 prior to MyoD may
      contribute to the incomplete myogenesis in the presence of lactacystin. In
      addition, lactacystin-treated C2C12 cells did not undergo apoptosis, while
      proteasome accumulated in the nuclei of apoptotic cells but not in those of
      myotubes during mitogen-depleted differentiation. Further, lactacystin induced
      similarly incomplete differentiation in human RD embryonal rhabdomyosarcoma
      cells. Our findings demonstrated that proteasome has an essential role in
      myogenesis, especially in transcriptional control of myogenic and cell cycle
      regulators, cell fusion forming myotubes, and apoptosis.

PMID- 9917520
TI  - Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable
      alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring.
AB  - Clinical trials have started to implement tumor-associated antigens in the form
      of antigenic peptides in order to augment CD8(+) T-cell responses directed
      against autologous cancer cells. One of the surrogate markers for successful
      immunization is the characterization of T-lymphocytes reacting to the immunizing
      peptide as determined by CDR3-length and DNA-sequence analysis. Most of the
      recent studies examining ex vivo T-cell responses in patients with cancer have
      focussed on expression and prevalence of the TCR Beta variable region,
      predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell
      receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appear
      to be predominantly present in the CD8(+) T-cell population and that these clonal
      TCRs are preferentially TCR-VA chains. This has been found to be true for PBL
      obtained from normal healthy subjects or from patients suffering from cancer, as
      well is in tumor specimens obtained from patients with cervical cancer. We
      suggest that a detailed analysis of the TCR-repertoire in patients undergoing
      immunotherapy, should include: i) examination of both TCR VA and VB families. ii)
      The absence of TCR VA or VB families should be noted and iii) these studies
      should be performed on CD4(+) or CD8(+) sorted T-cells or, if tissue specimens
      are analyzed, should be accompanied by a CD4 and CD8 staining.

PMID- 9917521
TI  - X-irradiation enhances the expression of Bcl-2 in HL-60 cells: the resulting
      effects on apoptosis and radiosensitivity.
AB  - Although p53 has been shown to directly activate transcriptional bax gene and to
      inhibit expression of bcl-2 gene during radiation-induced apoptosis, it is poorly
      understood how the Bcl-2 family changes in p53-deficient cells during radiation
      induced apoptosis. The present work describes the effect of X-irradiation on the
      apoptosis of p53-deficient HL-60 cells as assessed by means of several methods.
      Apoptosis of HL-60 cells was induced by X-irradiation in a dose- and time
      dependent manner. 18 h after 5 Gy irradiation, G2 cells underwent apoptosis,
      while 15 Gy X-irradiation induced the death of G1/S cells by 6 h. After X
      irradiation, expression of Bcl-2 was elevated, while Bax expression was
      unchanged. We have isolated a clonal HL-60 variant following twice 5 Gy
      irradiation of HL-XR3 cells. These cells highly expressed Bcl-2 (about 2-fold),
      showed a reduced activation of caspase-3, and were not only more resistant to X
      irradiation-induced apoptosis but also more radioresistant. These results suggest
      that HL-60 cells may resist apoptosis and radiation by increasing Bcl-2
      expression, and that this elevated Bcl-2 expression might be one of the causes of
      the phenomenon, often seen clinically, that tumor cells gradually acquire
      radioresistance during fractionated radiation therapy.

PMID- 9917522
TI  - Increased number of cardiomyocytes in cross-sections from tachycardia-induced
      cardiomyopathic hearts.
AB  - Based on positive identification of DNA replication and mitotic division in
      cardiomyocytes isolated from failing hearts, it has been proposed that adult
      ventricular cardiomyocytes can gain the capacity to proliferate with progression
      of heart failure. However, due to the lack of a reliable method to distinctly
      image individual cardiac cells within the myocardial syntitium, such a concept
      still remains largely controversial. In the present study, we used laser confocal
      microscopy, to image cross-sections of intact myocardium stained with fluorescein
      conjugated wheat germ agglutinin and propidium iodide. This approach allowed to
      clearly separate the profile of individual myocytes within cardiac tissue
      sections. We found that in the left ventricles of dogs, subjected to tachycardia
      induced cardiomyopathy, the number of cells was significantly increased in both
      longitudinal and transversal sections. Treatment with the angiotensin-converting
      enzyme inhibitor, enalapril, reversed these changes to values similar to those
      found in controls. Therefore, this study provides evidence, at the in situ level,
      for cellular hyperplasia in heart failure. This supports the more general notion
      that adult cardiomyocytes may not be terminally differentiated, and that an
      increase in cell number could contribute to the increase in left ventricular mass
      observed with progression of disease.

PMID- 9917523
TI  - Prognostic significance of the MIB-1 labeling index for patient with
      craniopharyngioma.
AB  - Proliferative activity of 17 craniopharyngiomas were determined using an
      immunohistochemical method with monoclonal antibody MIB-1. A considerable
      variation of the MIB-1 labeling indices was found between the different tumors
      with a minimum of 0.4% and a maximum of 32.5% (median, 10.84%). The mean MIB-1
      labeling index (LI) for 4 craniopharyngiomas that showed no evidence of
      recurrence (n=4) was 3.4 +/- 2.3%. This was significantly lower than that for
      craniopharyngiomas that showed recurrence and regrowth (13.2 +/- 7.7%) (n=13),
      based on the initial resected tumors. Statistical analysis reveal that
      craniopharyngiomas with an MIB-1 LI of 7% or more have a significantly high
      tendency for recurrence and regrowth during clinical course. Our data suggest
      that a MIB-1 LI greater than 7% may be a useful predictor of regrowth/recurrence
      of craniopharyngiomas and may be useful for planning of adjuvant therapy.

PMID- 9917524
TI  - Carcinogenic aspect of xenobiotic molecules belonging to the peroxisome
      proliferator family.
AB  - It is known that a short-term exposure of rat, mice or incubation of hepatic
      cells with fibrate molecules leads to increase in peroxisome number and cell
      hyperplasia. Further, long-term incubation of cells (at least a year) show
      transformed characteristics with foci and nodules. To explain the
      hepatocarcinogenic effect of peroxisome proliferators in rodents we studied the
      effect of peroxisome proliferators on rat liver oncogenes expression. Earlier, we
      reported an increase in liver and kidney mRNA level of c-myc and N-myc. Since
      several metabolic genes are activated by PPAR (peroxisome proliferators activated
      receptor) through a PPRE (peroxisome proliferator response element), we suggest
      the involvment of PPAR in oncogene activation, because of the presence of PPRE in
      the N-myc 5'-upstream region. We showed by flow cytometric analysis that
      ciprofibrate increased the size of rat Fao derived cell line and the activity of
      palmitoyl CoA oxidase, a peroxisome proliferation enzyme marker for studying
      peroxisome proliferation was increased. The above effects which can contribute to
      hepatocarcinogenesis seem to be restricted to rat and mice, which show strong
      response to peroxisome proliferators. Indeed, no changes are observed in weak
      responsive species such as humans (using hepatic derived cell lines) and guinea
      pig. These data provide arguments for the non-carcinogenic effect of this
      xenobiotic class in human especially when sensitive, or normal individuals are
      exposed either to hypolipidaemic agents of the fibrate family.

PMID- 9917525
TI  - DNA damage induced by Salmonella test-negative carcinogens through the formation
      of oxygen and nitrogen-derived reactive species (review).
AB  - High levels of active oxygen species generated by carcinogenic chemicals can
      cause DNA damage, which may lead to carcinogenesis. We have investigated the
      characteristics and mechanisms of DNA damage induced by some carcinogens. Here we
      show our experimental results and propose the possible mechanisms of DNA damage
      through a) NADH-dependent and b) manganese-dependent formation of reactive oxygen
      species. We also discuss the mechanism of c) DNA damage induced by nitric oxide
      and peroxynitrite.

PMID- 9917526
TI  - Increased growth of Bifidobacterium and Eubacterium by germinated barley
      foodstuff, accompanied by enhanced butyrate production in healthy volunteers.
AB  - Germinated barley foodstuff (GBF) derived from the aleurone and scutellum
      fractions of germinated barley mainly consists of low-lignified hemicellulose and
      glutamine-rich protein. GBF improves the proliferation of intestinal epithelial
      cells and defecation, through the bacterial production of short chain fatty acids
      (SCFA), especially butyrate. In this study we investigated the mechanism of
      production of butyrate by microflora in humans and in vitro. Daily administration
      of 9 g GBF for 14 successive days significantly increased fecal butyrate content.
      Fecal Bifidobacterium and Eubacterium were also significantly increased by GBF
      administration in healthy volunteers. Ten anaerobic micro-organisms selected from
      intestinal microflora were cultured in vitro in the medium containing GBF as a
      sole carbon source (GBF medium). After a 3-day incubation, 7 strains
      (Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus,
      Lactobacillus casei subsp. casei, Bacteroides ovatus, Clostridium butyricum, and
      Eubacterium limosum) lowered the medium pH producing SCFA. Eubacterium grown
      together with Bifidobacterium in GBF medium efficiently produced butyrate. On the
      other hand, GBF changed the intestinal microflora and increased probiotics such
      as Bifidobacterium in the intestinal tract. As a result, butyrate was produced by
      the mutual action of Eubacterium and Bifidobacterium. This butyrate is considered
      to enhance the proliferation of colonic epithelial cells.

PMID- 9917527
TI  - Effects of alpha-D- and beta-L-glucose pentaacetate on effluent radioactivity
      from pancreatic islets labelled with [(32)P]phosphate and myo-[2-(3)H]inositol.
AB  - The anomers of both D-glucose pentaacetate and L-glucose pentaacetate were
      recently found to display insulinotropic potential. In order to progress in
      understanding the mode of action of these esters in islet cells, we have now
      investigated whether they mimic the effect of nutrient secretagogues to cause a
      phosphate flush and activation of phospholipase C in isolated islets. For this
      purpose, rat pancreatic islets were prelabelled with either [(32)P]orthophosphate
      or myo-[2-(3)H]inositol and placed in a perifusion chamber. In the absence of any
      other exogenous nutrient, the administration of alpha-D-glucose pentaacetate (1.7
      mM) from 46 to 70 min of perifusion increased, after an initial transient fall,
      both 32P and 3H fractional outflow rates and stimulated insulin release from the
      perifused islets. No secondary rise in either (32)P or (3)H outflow and no
      sizeable stimulation of insulin release was observed, however, in response to
      Beta-L-glucose pentaacetate (also 1.7 mM). These findings are consistent with the
      view that the insulinotropic action of alpha-D-glucose pentaacetate entails a
      nutrient-like component leading to the occurrence of both a phosphate flush and
      hydrolysis of phosphoinositides. This is not the case, however, for Beta-L
      glucose pentaacetate. The latter ester might act directly on a yet unidentified
      receptor, the early secretory response to alpha-D-glucose pentaacetate also
      apparently involving such a direct effect of the ester itself.

PMID- 9917528
TI  - Renal bradykinin receptors: localisation, transduction pathways and molecular
      basis for a possible pathological role (review).
AB  - Kinins are biologically active peptides that exert their effects by activating
      two seven transmembrane G-protein coupled receptors termed B1 and B2 which have
      only about 36% of homology. The major kinin peptide under physiological
      conditions, bradykinin (BK), modulates renal haemodynamics and function. Under
      physiological conditions most BK effects involve bradykinin B2-receptors. Studies
      on the intra-cellular transduction pathways, the regulation of the expression and
      the localisation of these receptors along the nephron, as well as the first
      studies on transgenic mice models, have allowed to better define the role of
      these receptors under physiological and pathological conditions. The role of the
      renal B1-receptor, induced in a variety of pathologies related to inflammation,
      is poorly understood. Recent investigations on the molecular mechanism of B1
      receptor induction and its detailed renal localisation have shown that under
      inflammatory conditions this kinin receptor might be of importance. B2-receptors
      are suggested to be involved in part of the renoprotective effects of angiotensin
      converting enzyme (ACE)-inhibitors in insulin-dependent diabetes. However, ACE
      inhibitor treatment, resulting also in an increased B1-agonist concentration
      might result in homologous induction and activation of the B1-receptor.

PMID- 9917529
TI  - Exchangeability of accessory Vif and Vpu proteins between various HIV/SIVs
      (review).
AB  - Representative human and simian immunodeficiency viruses (HIV/SIVs) have been
      monitored for their Vif and Vpu activities in a wide variety of cells. In
      contrast to the prototype HIV-1, viruses of the other groups do not necessarily
      have these activities. Only HIV-2 and SIVmnd were clearly demonstrated to show
      the Vif and Vpu activities, respectively. The exchangeability of these accessory
      activities between viruses was then assessed to determine the relatedness of the
      viruses. Quite different from the results for Tat and Rev trans-activators, the
      activities are almost fully compatible between viruses. These results may
      facilitate the functional grouping of various HIV/SIVs.

PMID- 9917530
TI  - Molecular cloning and characterization of the pig secretor type alpha
      1,2fucosyltransferase (FUT2).
AB  - The existence of at least two distinct alpha 1,2fucosyltransferases has been
      postulated for many years, and recently confirmed in humans with the cloning of
      the human and rabbit secretor type alpha 1,2fucosyltransferase. We now describe
      the cloning and analysis of PFUT2, the pig secretor type alpha
      1,2fucosyltransferase, which shows a high level of amino acid identity with
      previously cloned alpha 1,2fucosyltransferases, but more so with human and rabbit
      FUT2. Expression of PFUT2 in COS cells showed cell surface staining for H
      substance with UEAI lectin and anti-H monoclonal antibody, but not for A blood
      group substance. Kinetic studies were consistent with PFUT2 having a preference
      for type 1 and type 3 acceptors, as do the human and rabbit homologues, in
      contrast to PFUT1 which shows a preference for type 2 substrates. Like HuFUT1 and
      PFUT1, PFUT2 was able to dominate over the pig alpha 1,3galactosyltransferase in
      co-expression studies in COS cells and give preferential expression of H
      substance and reduced expression of Gal alpha (1,3)Gal. Cotransfection studies
      demonstrate that a combination of FUT1 and FUT2 cDNAs has an additive effect in
      suppressing expression of Gal alpha (1,3)Gal.

PMID- 9917531
TI  - Increased production of interleukin-6 by adherent and non-adherent mononuclear
      cells during 'natural fatigue' but not following 'experimental fatigue' in
      patients with chronic fatigue syndrome.
AB  - In an investigator-blinded study, adherent (monocytes) and non-adherent cells
      (lymphocytes) from patients with chronic fatigue syndrome (CFS) were examined on
      two separate occasions (when feeling 'fatigued' and when feeling 'rested') for in
      vitro spontaneous, phytohemagglutinin- (PHA, for lymphocytes), and
      lipopolysaccharide- (LPS, for monocytes) induced production of IL-6 by ELISA
      assay. A group of CFS patients and controls were also subjected to exercise
      induced fatigue ('experimental fatigue') and IL-6 production was compared, in a
      double-blinded manner, prior to and following induction of fatigue. A significant
      increase in spontaneous, PHA- and LPS-induced IL-6 secretion by both lymphocytes
      and monocytes was observed in CFS patients during 'natural fatigue' as compared
      to during state. However, no such changes in IL-6 production were observed during
      'experimental fatigue'. These data suggest a role of IL-6 in natural
      symptomatology and perhaps in the pathogenesis of CFS. In addition, the data
      demonstrate that laboratory-induced fatigue (experimental fatigue) may not be a
      good model to study immunological changes in CFS; immunological parameters should
      be studied in a longitudinal manner during the natural course of the disease.

PMID- 9917532
TI  - Heterogeneous expression of P450 2C12 mRNA in female rat liver.
AB  - The heterogeneous expression of P450 2C12 mRNA was studied in the rat liver.
      Liver was sampled from female rat, approximately 40 mg portions being removed
      from 18 different locations. Total RNA was isolated and subjected to northern
      blot analysis. The membrane was hybridized with a (32)P-labeled rat P450 2C12
      gene-specific oligonucleotide probe. After the hybridized P450 2C12 gene-specific
      probe had been washed out, the membrane was hybridized again with a rat
      oligonucleotide probe for the detection of actin mRNA expression. In comparison
      with actin mRNA expression, P450 2C12 mRNA was not evenly expressed throughout
      the 18 different locations in the liver. The present results show the
      heterogeneous expression of P450 2C12 mRNA in the rat liver.

PMID- 9917533
TI  - Trace elements in hemodialysis and continuous ambulatory peritoneal dialysis
      patients.
AB  - Alterations in blood and tissue concentrations of trace elements in patients with
      chronic renal failure have been extensively investigated. Selenium, zinc and
      copper are elements which play an important role in biological systems as
      components of proteins, enzymes and antioxidants. The concentrations of selenium,
      zinc and copper were determined in the plasma, erythrocytes and whole blood of
      patients on regular hemodialysis (HD) and continuous ambulatory peritoneal
      dialysis (CAPD) treatment using the method of inductively coupled plasma mass
      spectrometry (ICP-MS). Analysis of isotopes 77Se, 66Zn and 65Cu was performed.
      Methodology presents the major limitation to valid studies on trace element
      levels in biological materials. One of the widely used contemporary techniques is
      ICP-MS. It is the most sensitive one and has a high dynamic range. The selenium
      concentration in the studied compartments (plasma 46.1 +/- 3.0 vs. 78.0 +/- 3.4
      microgram/l, p < 0.001; erythrocytes 90.4 +/- 6.5 vs. 134.2 +/- 7.6 microgram/l,
      p < 0.01; whole blood 67.3 +/- 3.1 vs. 106.4 +/- 3.4 microgram/l, p < 0.001) was
      significantly lower in HD patients compared to healthy controls. The same result
      was observed in plasma (63.2 +/- 5.8 vs. 78.0 +/- 3.4 microgram/l, p < 0.05) and
      whole blood (82.7 +/- 7.4 vs. 106.4 +/- 3.4 microgram/l, p < 0.01) from CAPD
      patients, but the selenium level of erythrocytes in CAPD patients was the same as
      in the control group (126.0 +/- 8.8 vs. 134. 2 +/- 7.6 microgram/l). The cooper
      content of erythrocytes was lower in HD patients than in controls (0.55 +/- 0.02
      vs. 0.66 +/- 0.01 mg/l, p < 0.01) and CAPD groups (0.55 +/- 0.02 vs. 0.68 +/-
      0.02 mg/l, p < 0.001). There were no differences in copper content in plasma (HD
      1. 02 +/- 0.06; CAPD 1.11 +/- 0.09; controls 1.02 +/- 0.05 mg/l) and whole blood
      (HD 0.87 +/- 0.04; CAPD 0.90 +/- 0.05; controls 0.85 +/- 0.02 mg/l) in HD and
      CAPD patients and healthy controls. The zinc concentration was increased in the
      whole blood of CAPD patients (6. 68 +/- 0.36 vs. 5.52 +/- 0.11 mg/l, p < 0.001)
      and erythrocytes of HD (12.30 +/- 0.23 vs. 10.11 +/- 0.42 mg/l, p < 0.001), and
      CAPD groups (13.71 +/- 0.56 vs. 10.11 +/- 0.42 mg/l, p < 0.001) compared to
      controls. However, the plasma zinc concentration was lower in HD patients
      compared to blood donors (0.69 +/- 0.03 vs. 0.92 +/- 0.03 mg/l, p < 0.001) and
      CAPD patients (0.69 +/- 0.03 vs. 0.95 +/- 0.04 mg/l, p < 0.001). We did not find
      a significant increase in trace elements in whole blood after HD. These results
      suggest differences between plasma, erythrocytes and whole blood concentrations
      of the studied trace elements. The levels of trace elements are altered by HD and
      CAPD. A modern precise method with high accuracy, ICP-MS, which was used in our
      study, eliminated analytical errors and possible interferences.

PMID- 9917534
TI  - Cytokine filtration and adsorption during pre- and postdilution hemofiltration in
      four different membranes.
AB  - In the present in vitro study we investigated filtration and adsorption of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8)
      during predilution and postdilution hemofiltration with polysulfone,
      polyacrylonitrile, polyamide and cellulose triacetate membranes. The median
      sieving coefficient (SC) for all membranes was 0.0 for TNF-alpha, below 0.15 for
      IL-6 and below 0.15 for IL-8 during postdilution hemofiltration. Differences in
      SC between filtration modes were less than 0.05. Maximal differences in SC
      between membranes were 0.11 for IL-6, 0.0 for TNF-alpha, and 0.11 for IL-8. The
      progressive decrease in cytokine concentrations was identical between the two
      filtration modes and most pronounced with the polyacrylonitrile membrane
      (reduction 77% for IL-6, 39% for TNF-alpha and 95% for IL-8 after 4 h of
      hemofiltration). The relative contribution of adsorption to the reduction in
      cytokines was 100% for TNF-alpha for all membranes, between 53 (cellulose
      triacetate) and 83% (polyacrylonitrile) for IL-6, and for IL-8 between 0
      (polysulfone) and 100% (polyacrylonitrile). In conclusion, the reduction in TNF
      alpha, IL-6 and IL-8 was most impressive with the polyacrylonitrile membrane
      after 4 h of hemofiltration and was largely due to adsorption. Adsorption of TNF
      alpha, IL-6 and IL-8 was also seen with the other membranes. None of the
      membranes filtered TNF-alpha. Sieving of IL-6 and IL-8 was low for all membranes
      with only marginal differences between membranes or between filtration modes.

PMID- 9917536
TI  - Compliance in hemodialysis patients: unanticipated monitoring of biochemical
      indices.
AB  - Compliance with the prescribed medical regimen is a critical factor for the
      continued well-being of hemodialysis patients. As compliance is a multifactorial
      problem, numerous approaches have been utilized to quantify the compliance of
      hemodialysis patients. In the present study, we have attempted to examine whether
      unanticipated control of biochemical indices might predict the compliance status
      of hemodialysis patients. We compared unanticipated mid-month values of blood
      urea nitrogen (BUN), serum potassium (K) and phosphate (PO4) values of 54
      maintenance hemodialysis patients with the scheduled, regular first-week
      measurements during a 6-month study period. The interdialytic weight gain (IWG)
      levels of the corresponding weeks were also compared. Mid-month analysis revealed
      a significant deviation in the compliance status of the study population as BUN,
      serum K and IWGs were concerned (p < 0.05). The mid-month serum PO4 levels were
      also higher but the difference was not significant (p < 0.05). In conclusion, the
      differences observed in biochemical indices upon change of test request timing
      were distinctive. It suggests that unanticipated control of biochemical indices
      might contribute to the actual assessment of compliance in hemodialysis patients.

PMID- 9917535
TI  - Effects of hemodialysis on circulating adrenomedullin concentrations in patients
      with end-stage renal disease.
AB  - To characterize the determinants of circulating levels of adrenomedullin (AM),
      the plasma levels of this peptide were measured in 58 patients with end-stage
      renal disease on hemodialysis. Predialysis plasma levels of AM were more than
      twice as high in patients on hemodialysis as compared to controls. In
      hemodialysis patients with heart failure (NYHA classes II-IV) or hypertensive HD
      patients plasma levels of AM were significantly higher than in patients with end
      stage renal disease only. Plasma levels of AM were not altered immediately by
      hemodialysis but decreased significantly 14-20 h after hemodialysis. AM plasma
      levels before hemodialysis and 14-20 h after hemodialysis were correlated with
      the corresponding mean arterial pressure.

PMID- 9917537
TI  - Systemic vascular resistance in intradialytic hypotension determined by means of
      impedance cardiography.
AB  - BACKGROUND: Recurrent intradialytic hypotension still is a major source of
      discomfort in hemodialysis patients today, its origin being subject to extensive
      research. Different hypotheses have been raised to unravel this problem, without
      forming one coherent point of view. The aim of this study was to gain more
      insight into the mechanisms causing intradialytic hypotension by determining
      cardiovascular performance noninvasively during hemodialysis in a large group of
      patients. METHODS: In the present study the variations in blood volume, stroke
      volume, cardiac output and systemic vascular resistance were investigated in 68
      patients on chronic intermittent hemodialysis utilizing bioelectrical impedance
      cardiography. In addition, blood volume was monitored continuously with an on
      line optical device. RESULTS: Twenty-four patients experienced symptomatic
      hypotension during dialysis treatment. Compared to the hemodynamically stable
      patients, the hypotensive patients manifested a slightly greater decline in blood
      volume (mean +/- SEM; -9.4 +/- 1.2 vs. -6.5 +/- 0.8%, p = 0.04) and cardiac
      output (-11.8 +/- 4.2 vs. -7.3 +/-2.7%, p = NS). The main difference, however,
      was a highly significant decrease in systemic vascular resistance (-17.9 +/-
      4.4%) in the hypotensive group compared to a rise in the stable group (+6.2 +/-
      3.5%, p < 0.001). CONCLUSION: Intradialytic hypotension seems the consequence of
      an inadequate compensatory response to ultrafiltration-induced blood volume
      reduction, resulting in a fall in systemic vascular resistance. The degree of
      hypovolemia itself appears to be less important in the origin of acute,
      intradialytic hypotensive episodes. Noninvasive monitoring during hemodialysis
      provides an opportunity to gain more insight into the pathophysiology of
      intradialytic hypotension and offers the possibility for controlled intervention
      and possible prevention of this complication.

PMID- 9917538
TI  - Increase in resting levels of superoxide anion in the whole blood of uremic
      patients on chronic hemodialysis.
AB  - Recently, we developed a new method to measure the resting level of superoxide
      anion in whole blood using an ultrasensitive chemiluminescence analyzer and
      lucigenin amplification. The advantage of this method is that the assay system
      can be performed in the absence of leukocyte isolation and stimulant
      administration. In this study, we applied this method to measure the blood
      resting levels of superoxide anion in 104 uremic patients on chronic hemodialysis
      (CHD) and 98 sex- and age-matched healthy controls to clarify the influence of HD
      on blood levels of superoxide anion. Simultaneously, the plasma levels of copper,
      zinc superoxide dismutase (Cu,Zn-SOD), glutathion peroxidase (GPX),
      myeloperoxidase (MPO) and lactoferrin (Lacto-F) were measured. The results showed
      that the basal blood levels of superoxide anion, Cu,Zn-SOD, and MPO in CHD
      patients were significantly greater than those of healthy controls. However,
      there was no difference in the basal plasma levels of Lacto-F and GPX between CHD
      patients and healthy controls. One session of HD further increased the blood
      levels of superoxide anion, MPO, Lacto-F and Cu,Zn-SOD but not GPX. These results
      suggest that the blood levels of superoxide anion are higher in CHD patients and
      further increase after one session of HD. This mechanism should be studied
      further.

PMID- 9917539
TI  - American Society of Pediatric Neurosurgeons--change at the millennium.

PMID- 9917541
TI  - Frontal and occipital horn ratio: A linear estimate of ventricular size for
      multiple imaging modalities in pediatric hydrocephalus.
AB  - OBJECTIVE: Measurement of ventricular size is important in pediatric patients
      with hydrocephalus, especially those who are being followed with cerebrospinal
      fluid (CSF) shunts. While volumetric techniques are a more accurate estimate of
      true ventricular volume, they are often impracticable when multiple modalities
      including ultrasound are used. Volumetric area and linear measurements were
      compared to find the most reasonable measurement method. METHODS: Sixty-four
      computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US)
      scans from 25 children aged 0-17 years with hydrocephalus, before and after
      treatment, were measured. Measurements included ventricular volume, a
      ventricular/brain ratio, and four standard linear measures (Evans' ratio,
      Huckman's measurement, minimal lateral ventricular width, and lateral ventricular
      span at the body). We also included a new ratio, which accounts for often
      disproportionate occipital horn expansion in pediatric patients, called the
      frontal and occipital horn ratio. Volume and linear measurements were compared
      using the Spearman's correlation coefficients and correlations were further
      differentiated using a Z test statistic. The frontal and occipital horn ratio was
      also measured on CT, MRI, and US scans from 44 normal children aged 0-17 years to
      identify normal values. The effect of age was determined by linear regression.
      RESULTS: The best linear correlation with ventricular size was the frontal +
      occipital horn ratio (r = 0.852) and was equivalent to the ventricular/brain
      ratio (r = 0.891), previously shown to have the highest correlation with
      ventricular volume. Evans' ratio correlates less well (r = 0.423). The normal
      frontal and occipital horn ratio is 0.37 and is independent of age. CONCLUSIONS:
      The frontal and occipital horn ratio is a simple method of evaluating ventricular
      size in pediatric hydrocephalus patients with CSF shunts.

PMID- 9917540
TI  - Application of signal transduction inhibition as a therapeutic strategy for
      central nervous system tumors.
AB  - During the last decade, rapid progress has been made in understanding the
      molecular pathways underlying the proliferation of both normal and neoplastic
      cells. The processes by which messages to initiate protein synthesis, cell cycle
      progression, and even cell death are transmitted from the cell surface or the
      cytoplasm to the nucleus are broadly referred to as 'signal transduction'. These
      multistep pathways involve a host of proteins that interact with other proteins
      in overlapping cascades that flow downstream in a stepwise fashion from the cell
      membrane to the nucleus. Inappropriate overactivation or underactivation of
      various components of such signaling pathways can contribute to pathological
      processes, such as neoplasia. Conversely, molecular and pharmacological
      interventions that target and attempt to reverse the aberrant state of activation
      can potentially be of therapeutic benefit. The present article provides a
      background for understanding the contribution of signal transduction pathways to
      the proliferation of normal and neoplastic cells and describes ways in which
      targetted inhibition of selected signaling pathway components has been exploited
      to inhibit tumor growth in vitro and in vivo. Because most studies to date
      involving central nervous system (CNS) tumors have focused on gliomas, in view of
      their frequency in both the pediatric and adult age groups, the discussion of
      therapeutic applications for CNS neoplasia will deal primarily with these
      lesions. However, the basic concepts presented are generalizable to most tumor
      types and have been successfully applied in vitro in medulloblastomas as well.
      Ultimately, the translation of such strategies to the treatment of patients with
      malignant brain tumors may provide novel approaches for improving the poor
      outlook associated with these neoplasms.

PMID- 9917542
TI  - Primary Ki-1-positive T-cell lymphoma of the brain in a child.
AB  - A unique case of a female child with primary Ki-1-positive T-cell lymphoma of the
      brain is reported. Her clinical course is discussed and the previous literature
      is reviewed.

PMID- 9917543
TI  - High-field strength interventional magnetic resonance imaging for pediatric
      neurosurgery.
AB  - BACKGROUND: Interventional magnetic resonance (MR) imaging allows neurosurgeons
      to interactively perform surgery using MR guidance. High-field (1.5-Tesla)
      strength imaging provides exceptional visualization of intracranial and spinal
      pathology. The full capabilities of this technology for pediatric neurosurgery
      have not been defined or determined. MATERIALS AND METHODS: From January 1997
      through June 1998, 10 of 85 cases performed in the interventional MR unit were in
      the pediatric population (mean age 8.3, median 8, range 2-15 years). Procedures
      included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for
      syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The
      biopsies and reservoir placement were performed using MR-compatible equipment.
      Craniotomies and spinal surgery were performed with conventional instrumentation
      outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging
      was performed to assess the goals of surgery. RESULTS: Both brain biopsies were
      diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was
      optimally placed within the tumor cyst. Of the 5 tumor resections, all were
      considered radiographically complete. One biopsy patient and 1 tumor resection
      patient experienced transient neurological deficits after surgery. The patient
      with the thoracic syrinx required reoperation when the syringosubarachnoid shunt
      migrated into the syrinx 3 months after initial placement. No patient sustained a
      postoperative hemorrhage. Tumor histologies found at craniotomy were
      craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor
      progression has been seen in any of these patients at a mean follow-up of 5.3
      (range 4-8) months. The goals of the procedure were achieved in all 10 cases.
      There were no untoward events experienced related to MR-compatible
      instrumentation or intraoperative patient monitoring, despite the present
      inability to monitor core body temperature. CONCLUSIONS: 1.5-Tesla interventional
      MR is a safe and effective technology for assisting neurosurgeons to achieve the
      goals of pediatric neurosurgery. Preliminary results suggest that surgical
      resection of histologically benign tumors is enhanced in the interventional MR
      unit. The incidence of surgically related morbidity is low.

PMID- 9917544
TI  - Pathogenesis of arachnoid cyst: congenital or traumatic?
AB  - For clarifying the pathophysiology of arachnoid cysts and reestablishing
      therapeutic criteria for such cases, we reviewed a series of 90 cases with
      arachnoid cysts focusing on the traumatic origin. Arachnoid cysts of congenital
      origin have been well known. But we suspected that 14 out of 90 patients (15.6%)
      with arachnoid cyst were closely related to head trauma. Seven of them suffered
      from head traumas in infancy. The episodes of head trauma included falling down
      in 4 patients, slipping down in 2 patients, and a motor vehicle accident in 1
      patient. Traumatic arachnoid cysts had a latent period from head trauma to
      initial clinical manifestation. The mean latent period was 2.2 years, ranging
      from 10 months to 6.2 years. Six of 7 arachnoid cysts were located in the
      suprasellar area and 1 at the posterior fossa. An other 7 patients had a history
      of perinatal trauma. We postulate that head trauma in infancy may contribute to
      the pathogenesis of arachnoid cyst in some cases.

PMID- 9917545
TI  - Abdominal cerebrospinal fluid pseudocyst: A complication of ventriculoperitoneal
      shunt in children.
AB  - The present paper is a retrospective analysis of 27 consecutive patients, treated
      for abdominal cerebrospinal fluid (CSF) pseudocyst at the Children's Memorial
      Hospital in the years 1991-1996. This series is compared to the previous
      experience from our institution. Treatment consisted of the removal of the
      ventriculoperitoneal (VP) shunt and placement of an external ventricular drain.
      Antibiotics were administered intravenously for 10 days. The cysts were aspirated
      intraoperatively in 9 patients and postoperatively with ultrasound guidance in 3
      patients, while they resolved spontaneously in 15 others. In 21 of 27 cases
      (78%), the shunt could be reinserted into the abdomen in a new location. Four
      patients had a ventriculopleural shunt, and in 2 patients, a ventriculoatrial
      shunt was inserted. Forty-four percent of the patients had a positive culture on
      presentation. The positive culture rate was 77% for those 4 years old and younger
      and only 28% for those aged 5 and above (p = 0.03). We conclude that abdominal
      CSF pseudocysts are resolved by externalizing the shunt. A VP shunt can be safely
      reinserted in the majority of the patients. Infection, while an important factor,
      is not likely to account for all cases of pseudocyst.

PMID- 9917547
TI  - Images in pediatric neurosurgery. Chiari I.

PMID- 9917546
TI  - Reduced hindbrain herniation after intrauterine myelomeningocele repair: A report
      of four cases.
AB  - BACKGROUND: It has been theorized that fetal myelomeningocele repair may reduce
      ongoing intrauterine injury and perhaps allow healing and regeneration of
      dysplastic neural tissue. We report on the postnatal imaging studies of the first
      4 patients to have undergone intrauterine myelomeningocele repair at our
      institution. METHODS: Each of the 4 patients underwent postnatal sonographic and
      MRI. In addition, the postnatal ultrasounds of these 4 were compared to a group
      of retrospective controls. RESULTS: MRI scans of the 4 experimental subjects
      revealed no evidence of hindbrain herniation while other stigmata of the Chiari
      II malformation persisted. In comparison to the retrospective controls this
      absence of herniation was distinctly unusual. CONCLUSION: Intrauterine
      myelomeningocele repair may reduce the degree of hindbrain herniation normally
      seen in patients with myelomeningocele. This raises the possibility that
      intrauterine repair may decrease the morbidity associated with the Chiari type-II
      malformation including brainstem dysfunction, hydrocephalus and syringomyelia.

PMID- 9917548
TI  - Technical note: meningomyelocele dressings.

PMID- 9917549
TI  - [Epithelial ovarian cancers (advanced stage)].
AB  - Ovarian carcinomas are known to have a poor prognosis, not only because their
      diagnosis is often made in late time, but the risk of recurrence after initial
      treatment is high. This overview was made to explain the different approaches
      while dealing with a patient with an ovarian carcinoma. A particular interest
      went to the familial history of ovarian cancer, concerning a very short
      population, as shown in the recent data. Prognostic factors, the way of
      diagnosis, and the histologic classification were also explained in detail.
      Ovarian cancer is more often found out at an advanced stage of the disease,
      that's the reason why the treatment of epithelial ovarian cancer was extensively
      studied, with the recent approaches of the new drugs; for instance, the use of
      combinations with taxoides in the first part of treatment, or a numerous of other
      agents, particularly at the time of the recurrence, like the camptothecines, the
      gemcitabine, or the new derivatives of platinum. The management of the patient
      after initial treatment (follow up, maintenance therapy) were also included in
      this overview. As for the "borderline" tumors, a peculiar chapter was devoted to
      them.

PMID- 9917550
TI  - [Infiltrating carcinoma of the uterine cervix: epidemiology, prognostic factors,
      therapeutic strategies].
AB  - In industrialized countries cervical cancer has decreased over the past decades.
      This, thanks to wide spread screening campaigns of precancerous lesions and
      microinvasive diseases through regular pap smears starting from the beginning of
      sexual activity. The diagnostic is realized earlier, thus increasing the rate of
      curability. Unfortunately, the absence of such programs in underdeveloped
      countries has made cervical cancer the second cause of death by cancer among the
      world female population. This general review treats in a non exhaustive manner
      epidemiology and prognostic factors and secondly exposes the therapeutic methods
      that has become available in recent years.

PMID- 9917551
TI  - [Carcinoma of the endometrium: review of the literature].
AB  - In endometrial adenocarcinoma, many risk factors have been demonstrated. Among
      them, tamoxifene is a factor of low risk. Any endometrial bleeding requires a
      gynecological exam in order to make an early diagnosis. The positive histologic
      diagnosis is more often after surgery which is necessary for histo-prognostic
      stage. Non conservative hysterectomy with pelvic lymphadenectomy (obturator
      chain) is recommended for the most frequent stages I and II. Radiation therapy
      alone is recommended for stage III. Palliative therapy (hormonotherapy or
      chemotherapy) could be proposed for the few stage IV.

PMID- 9917552
TI  - [Methods for evaluating biological response modifiers].
AB  - Biological response modifiers (BRM) are a new approach of cancer treatment. The
      guidelines for their evaluation are comparable to those used for evaluating
      conventional anticancer treatments. However, it is more difficult to assess their
      efficacy and toxicity because of their own properties and of the characteristics
      of underlying diseases. The objectives of studying BRM efficacy are the following
      : 1- to confirm the pharmacodynamic effect observed in experimental models; 2- to
      assess the benefit for the patient. Phase II studies can occasionally be
      performed in healthy volunteers. Efficacy criteria are objective response rate,
      progression free survival, overall survival or, for hematopoietic growth factors,
      more specific criteria. In randomized phase III studies patients in the control
      arm can be observed without treatment, or receive a placebo or a standard
      treatment. As regards toxicity, side effects specifically related to the use of
      BRM are the synthesis of cytokines, the stimulation of immune system, the
      stimulation of tumor growth, the synthesis of anti-mouse of anti-BRM antibodies.

PMID- 9917553
TI  - [Hormonal replacement therapy and breast cancer].
AB  - Hormonal replacement therapy is prescribed more and more frequently to increase
      quality of life and decrease the symptomatic and organic consequences of the
      menopausal status. The different studies which analyzed the risk of breast cancer
      for women under hormonal replacement therapy show opposed conclusion. We reviewed
      articles published between 1980 and 1997 to try to conclude about the
      consequences of the action of this treatment in the risk of breast cancer from
      the characteristic of the hormonal replacement therapy and from known risk of
      breast cancer. Hormonal replacement therapy increases the incidence of breast
      cancer. Risk increase with the treatment duration and a low estrogen dose would
      be sufficient to palliate to the hormonal lack (< 0.625 mg/j). The risk of breast
      cancer becomes the same that this of women without hormonal replacement treatment
      when treatment interrupted. The association of estrogen and progestin should not
      be protective of breast cancer. But the hormonal treatment seems to be
      synergistic for the risk of breast cancer with late menopause, late age at the
      birth of first child. Hormonal treatment could increase the estrogenic period and
      should increased the risk of breast cancer in women with late age at menarche,
      late age at menopause and late age at first child. It should not increase the
      risk of breast cancer in women with benign breast disease, with family history of
      breast cancer and in nulliparous women. For women who undergone a bilateral
      oophorectomy before hormonal replacement treatment the risk would be the same
      than for women with natural menopause and without hormonal replacement treatment.
      However breast cancer should be diagnosed earlier in women with hormonal
      treatment because mammographies were made more frequently. Overall survival
      should not different between the women who were under hormonal therapy and theses
      were not.

PMID- 9917555
TI  - [Analysis of hematopoietic growth factor prescriptions in 19 french cancer
      centers].
AB  - Medical prescription of hematopoietic growth factors (HGF) was analysed in 19
      anticancer french centers during 2 months. About 4% of anticancer
      chemotherapeutic cycles prescribed during this period were supported by HGF
      prescription. The mean duration of treatment was 8 days. Among the 755 collected
      prescriptions, two tumor localizations represented about 50% of the
      prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main
      localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular
      cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis
      for febrile neutropenia remains the main use of HGF (44%). The respect of the
      guidelines established by the F|d|ration nationale des centres de lutte contre le
      cancer was analyzed. Overall, 66% of the prescriptions were in adequation with
      these guidelines. Whereas the consommation of HGF decreased in the 19 considered
      institutions, it did not reach a plateau and could decrease in institutions which
      are awaked to the international and national recommendations.

PMID- 9917554
TI  - [Standards, options and recommendations (SOR) for clinical care of
      rhabdomyosarcoma (RMS) and other soft tissue sarcoma in children. Federation of
      the French Cancer Centers. French Society of Pediatric Oncology].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. For pediatric issues, this
      project is a collaboration between the FNCLCC and the French Society of Pediatric
      Oncology (SFOP). The main objective is the development of clinical practice
      guidelines to improve the quality of health care and outcomes for cancer
      patients. The methodology is based on literature review and critical appraisal by
      a multidisciplinary group of experts, with feedback from specialists in cancer
      care delivery. OBJECTIVES: To develop a clinical practice guideline according to
      the definitions of Standards, Options and Recommendations for the clinical care
      of rhabdomyosarcoma and other soft tissue sarcoma in children and adolescents.
      METHODS: Data have been identified by literature search using Medline (1985-may
      1997) and experts group personal references lists. The main criteria considered
      were incidence, risk factors, prognostic factors and efficacy of cancer
      treatment. Once the guideline was defined, the document was submitted for review
      to 14 national and international independent reviewers, and to the medical
      committees of the 20 French Cancer Centres and, in particular the 4 which have
      expertise in pediatric cancer management, for agreement. RESULTS: The main
      recommendations for rhabdomyosarcoma management are: 1/ diagnosis is based on
      appropriate clinical and radiological findings; 2/ pathological and
      immunohistochemical studies are essential to confirm the diagnosis; 3/ surgery
      must be performed by an experienced surgeon. Surgery and radiotherapy must be as
      conservative as possible; 4/ therapeutic strategies for rhabdomyosarcoma depend
      on location and extends and are based on chemotherapy, surgery and radiotherapy.
      Inclusion of patients in SFOP, SIOP and IRS clinical trials is recommended; 5/
      treatment of metastatic rhabdomyosarcoma is based on intensive chemotherapy, and
      surgery with or without radiotherapy; 6/ the management of non-rhabdomyosarcoma
      is based on the likelihood of sensitivity to chemotherapy; 7/ at the present
      time, there are no clear data on which to base guidelines for timing and duration
      of follow-up studies in these conditions.

PMID- 9917557
TI  - [Informative value of Hemoccult test according to the number of positive slides
      in mass screening of colorectal cancer].
AB  - Our aim was to study the relationship between the level of positivity of the
      Hemoccult colorectal cancer screening test and the positive predictive value on
      one hand, and the characteristics of the screened neoplasms on the other. This
      study focuses on four successive colorectal cancer screening campaigns in a
      population of 45,642 subjects born between 1914 and 1943. There were 1 or 2
      positive slides in 50.1% of cases, 3 or 4 in 30.7% of cases and 5 or 6 in 19.2%
      of cases. The positive predictive value was 11.1% for cancer, 17.4% for adenoma >
      or = at 1 cm and 10.1% for adenoma < 1 cm. For a cancer or adenoma > or = at 1
      cm, the positive predictive value varied between 18.6% when there were 1 or 2
      positive slides, and 52.5% when there were 5 or 6 positive slides. Dukes A
      cancers are less likely to have 5 or 6 positive slides than more advanced
      cancers. On the contrary, neither cancer localisation nor characteristics of
      adenomas > or = at 1 cm (localisation, size, degree of dysplasia) influenced the
      number of positive slides. Owing to intermittent colorectal cancer bleeding, it
      seems necessary to take several successive samples. Two samples per stool over
      three successive stools seem like a good compromise. The informative value of the
      test increases with the number of positive slides.

PMID- 9917556
TI  - [Prostate cancer in Isere and Tarn (France) between 1985 and 1995: evolution of
      therapeutic indications].
AB  - The objective is to describe the evolution of therapeutic practices of prostate
      carcinoma in the departements of Tarn and Isere in France for the 1985-1995
      period. This retrospective study is based on patient folders for whom a prostate
      carcinoma has been diagnosed between 1985 and 1995. A sample of 871 patients have
      been included after randomisation stratified on the year and the department of
      the diagnostic in the files of the cancer registries of Tarn and Isere.
      Therapeutic practices of the prostate cancer have significantly evolved between
      1985 and 1989. The rate of radical prostatectomies increased from 1986 whereas
      the rate of radiotherapy remained stable. This evolution has been made to the
      detriment of non curative treatments with the decrease of the rate of
      hormonotherapies. This is due to the important development of diagnostic technics
      which led to an earlier diagnostic of these cancers; but, the evolution of
      therapeutic technics and particularly of the radical prostatectomy allowed the
      evolution of indications for the treatment of this cancer, with the increase of
      the rate of radical prostatectomies and the decrease of the rate of
      radiotherapies at the same stage of disease evolution. For 1990 to 1995, there
      was no major evolution. Some indications are discussed in this disease touching
      old man, with a slow evolution.

PMID- 9917558
TI  - [Sixth congress of the European Genetic Therapy Group].

PMID- 9917559
TI  - [Carboxypeptidase-G2 rescue of methotrexate intoxication].

PMID- 9917560
TI  - [Searching for p </=5 %].

PMID- 9917561
TI  - Transmission in utero of the hepatitis B virus in ivory coast the case for mass
      vaccination 
AB  - Background. Hepatitis B is a major public health problem in the developing
      countries of Africa and Asia because the prevalence of HBs antigen carriers is
      high. In Ivory Coast, the prevalence of HBs antigen carriers is more than 8% (6
      to 29%). In these countries, in which hepatitis B is highly endemic, most
      infections with hepatitis B virus (HBV) occur during early childhood. The chronic
      carriage of HBV was found to be common in children, who played a key role in
      maintaining the high level of endemicity in these areas. Vaccines against HBV are
      effective and their introduction as part of the Expanded Program of Immunization
      (EPI), as recommended by the WHO, is feasible. Objective. The aim of this study
      was to evaluate the prevalence of HBs antigen in pregnant women and to determine
      the rate of maternal transmission of HBV to the fetus, to demonstrate the
      importance of HBs antigen screening during pregnancy and the immunization of
      babies in the Ivory Coast. Patients and methods. Between August 1995 and February
      1996, 395 women in the last three months of pregnancy (age 25 6.9 years) were
      screened for HBs antigen. Those testing positive were also screened for HBe
      antigen. Transmission of HBV in utero was studied with 322 mothers and their
      offspring. HBs antigen was assayed in the cord blood of the offspring of HBs
      antigen-positive mothers. If the test for HBs antigen was positive, HBe antigen
      was also assayed. Second-generation ELISA tests (MONOLISA HBs Ag and MONOLISA HBe
      Ag from Sanofi Pasteur) were used. Babies from HBs antigen-positive mothers were
      vaccinated at birth with three doses of GenHevac B.

PMID- 9917562
TI  - The cost to families of the hospitalization of their child in niame 
AB  - In Niger, 54.4% of the population live below the poverty level (less than 750 FF
      per year per person). The government is currently implementing a policy to reduce
      medical costs, including those of hospitals. We carried out a study during the
      rainy and dry seasons of 1994-1995, of 80 children, randomly selected, who had
      been admitted to the pediatric ward of Niamey National Hospital. The total
      expenditure of their families, due to their hospitalization, was recorded and
      analyzed. The total expenses of the family were 151. 8 ( 100.0) to 185.5 ( 118.9)
      FF depending on where the drugs were purchased (wholesale or private). Medical
      expenses accounted for 98. 0 ( 48.3) to 119.8 ( 57.2) FF, that is 60.0 to 64.5%
      of total expenses. Non-medical expenses (transport, food, presents) accounted for
      61.7 to 65.7 FF, 35.4 to 39.9%. Total daily expenses were 23 to 41.7 FF for the
      five main diseases. In 66 cases, the costs were paid by the father (82.5%), with
      the mother or another person paying in 7 cases (8.8%). Only 24 families (30%)
      paid the hospital fee (10.5 FF). Twenty-seven families were exempted and 22
      avoided payment. The cost of medical analysis was 32.6 ( 31.3) FF and this was
      paid by the hospital. The total cost (total family expenditure + hospital
      expenditure) of a stay in a pediatric unit was 316.5 to 350.4 FF, which is
      equivalent to 8 to 10 times the mean annual individual expenditure on health in
      urban areas of Niger. Measures have already been introduced to encourage the
      prescription of generic drugs and a number of measures are currently under
      discussion for lowering the cost to families of hospital and health center care
      and for improving the cost effectiveness of treatment.

PMID- 9917563
TI  - Epidemics and colonial medicine in west africa 
AB  - We studied colonial medical practices and health policies in West Africa, which
      has faced endemics and epidemics that have affected entire societies. We found
      that attempts to centralize the organization of colonial medicine, which began in
      the late 19th Century, were limited until the end of World War I. Research and
      control programs expanded after 1920, concentrating on epidemics, but largely
      ignoring many major health problems, such as measles, whooping cough and
      malnutrition, the importance of which were not recognized until after World War
      II. This appraisal of colonial medicine highlights the difficulties of
      introducing modern medicine and its ideas into African societies. There have been
      various social reactions, resulting in the current duality in which traditional
      and modern medicine coexist.

PMID- 9917564
TI  - Space, health and territory in intertropical area 

PMID- 9917565
TI  - The senegalese cholera epidemic of 1995 to 1996, an example of the geographic
      approach to health studies 
AB  - There have been many cholera outbreaks in Senegal since 1971. The last outbreak
      began in the Dakar region in August 1995. It spread to the Diourbel, Fatick,
      Saint-Louis and Thies regions. In January 1996, the outbreak hit the Niakhar
      study area in the Fatick region. A team from ORSTOM (the French Institute of
      Scientific Research for Development in Cooperation) has been recording
      demographic events in this area for almost 15 years. The geographic approach is
      based on the automated mapping of cholera in hamlets and villages. Such studies
      investigate the factors determining the spread of diseases, within the context of
      land use. Three sets of data were used: demographic data that had been routinely
      collected and were available from a database, digitized maps and epidemiological
      data from a surveillance system set up to monitor the outbreak. A series of
      incidence maps, over time and on various scales, were generated using specialized
      software. The maps were analyzed and the outbreak was found to be heterogeneous
      over time. There were two waves of the outbreak and differences according to age
      and gender. The degree of heterogeneity depended on the place of residence.
      Heterogeneity was probably determined by village size, roads and the
      concentration of inhabitants within hamlets, which is roughly equivalent to the
      number of people per bore hole. These preliminary results suggest that further
      research is necessary, looking at different geographical scales (e.g. households,
      districts and regions). Qualitative studies of water use and the organization of
      the water supply are also required.

PMID- 9917566
TI  - Geographical determinants of onchocerciasis transmission in a forest/savannah
      transition zone : two villages of the mbam focus 
AB  - Mbam, a focus of onchocerciasis outbreaks, is located in the forest/savannah
      transition zone of Cameroon. Transmission of the disease in this area is similar
      to that sometimes observed in West Africa. Geographical factors affecting
      transmission must be identified to determine the areas for priority action. The
      locations of breeding sites for black flies (the vector of the disease) and
      factors favorable to their dispersion, the social behavior of these population
      and the way that she occupy space, must be investigated to identify areas in
      which the flies and man are in close contact. This geographical study shows that
      the closest contact between men and black flies occurs in cocoa plantations, due
      to the proximity of the breeding sites. The areas of closest contact for women
      and children are unknown, but their identification is important because women and
      children may be bitten by the flies during their daily activities.

PMID- 9917567
TI  - Acquired immune deficiency syndrome in brazil and the state of cear 
AB  - Since February 1998, a total of 129,000 cases of acquired immune deficiency
      syndrome have been reported in Brazil. The cumulative frequency of the disease is
      82 per 100,000, which makes Brazil one of the countries moderatly affected. There
      are considerable differences between regions in the frequency of cases, from 25
      per 100,000 in the north and north east to 152 per 100,000 in the south east.
      Sexual intercourse is still the predominant means of transmission. Transmission
      in the early years of the epidemic was mostly between homosexuals and bisexuals,
      but transmission via heterosexual intercourse is increasing. The contribution
      made by intravenous drug use differs between the regions, and is particularly
      large in the mid-south region. A pilot project in the city of Fortaleza has shown
      that it is possible to successfully integrate the diagnosis of STD and AIDS in
      health care units at an intermediate level. This appears to be an appropriate
      strategy for the integration of STD treatment into primary health care in Ceara
      State. The non-uniform pattern of development of this epidemic must be taken into
      account in epidemiological analyses of AIDS in Brazil.

PMID- 9917568
TI  - HIV-2 infection throughout the world. A geographical perspective 
AB  - The geographical distribution of HIV-2 is not fully understood. However, there is
      enough evidence to speculate about the origins and differentiation of this
      geographical pattern. Foci of infection probably developed in some African
      countries, such as Guinea-Bissau, Angola and Mozambique, in the 1970s. The
      decolonization of these countries led to the movement of people, and the virus,
      to historically associated countries such as Portugal, India and Brazil. In Ivory
      Coast, a focus was probably created due to the dismantling of the plantation
      economy, with all its demographic, cultural and social consequences. The virus
      was dispersed to countries close to the Guinea and Ivory Coast foci by the
      migration of workers and prostitutes. Thus, the diseases has spread from the
      Atlantic coast of Africa, where it was endemic-sporadic, to other more distant
      African countries and out of Africa into Europe and North America. The political
      emancipation of African countries is further increasing and diversifying human
      movements between countries. The infection has not created an epidemic, either
      within or outside Africa. This is due to the limited infectivity of the virus and
      the particular characteristics of the social and epidemiological system. The high
      risk groups do not sustain an epidemic relay of the infection and subjects
      introducing the virus into new areas outside the African foci rarely set up a new
      autonomous circulation of the virus.

PMID- 9917569
TI  - Geographic approach to urinary schistosomiasis in an average african town, daloa 
AB  - Agricultural activity occurs within many medium size towns in developing
      countries. Rural influences and urbanization, which may be well or poorly
      managed, combine to create new health problems. A geographical approach is useful
      for evaluating the ability of the health care system to deal efficiently with
      these problems. Such an approach should take into account the urban environment
      and human population, health care and spatial differentiation factors. Relevant
      health indicators were selected to analyze the geographical patterns of health
      risk and of the health care system. These factors were analyzed according to
      area, at various levels. Field studies were carried out and aerial photographs
      and the various available maps were also studied. Results were compared to
      determine whether the health care system was appropriate for the health needs of
      the town. Urinary schistosomiasis is a useful example for assessing the value of
      the suggested methodology. The risk of transmission of this disease is high so
      its early detection is vital. The ability of the health care system to detect
      infection was assessed.

PMID- 9917570
TI  - The contribution of a geographic approach to studies of the modern health care
      system of the republic of congo 
AB  - We carried out a geographic analysis of the modern health care system in the
      rural areas of Kouilou and Niari (Republic of Congo). Spatial differences in
      physical (e.g. vegetation, relief) and human (social and demographic profiles)
      factors must be characterized because they have an effect on the organization and
      spatial distribution of the health care system. The location of health care
      structures depended on the structure of the local environment. The health care
      system seemed primarily to be a component of the economic development determining
      population distribution in the forest area. In the savannah, it was part of the
      local administrative framework, the key factor determining the structure of the
      local space. Health care services were most used in areas with average to large
      population densities, in which there were the largest number of health care
      structures. Areas with "marginal" population densities and health care center
      distributions had the lowest rates of health care use. Health care zones can be
      defined by considering geographical characteristics and the characteristics of
      the health care system. This makes health planning (e.g. opening of health
      centers, improvement of health centers) much easier to undertake.

PMID- 9917571
TI  - Mapping epidemiological results. The principles behind methods to make continuous
      data discrete and their importance in cartographic representation 
AB  - The cartographic representation of continuous quantitative data is often required
      in studies of the spatial distribution of health indicators. It imposes a
      succession of choices which directly affect the result obtained. The conversion
      of continuous data to discrete data is one of the most important steps in the
      development of epidemiological maps. This article presents the methods currently
      used to make data discrete, discusses the advantages and disadvantages of each
      method and assesses their appropriateness for various situations. As an example,
      and for comparison purposes, we mapped the same series of statistics (relative
      rates of avoidable male deaths, "associated with the health care system", for
      "employment zones" in France from 1988 to 1992), using each of the methods
      discussed.

PMID- 9917572
TI  - ACE inhibitor therapy: benefits and underuse.

PMID- 9917573
TI  - Pros and cons of genetic screening for breast cancer.

PMID- 9917574
TI  - Sertraline in the treatment of obsessive-compulsive disorder.

PMID- 9917575
TI  - Maternal self-collection of specimens for GBS culture.

PMID- 9917576
TI  - Hepatitis C: Part I. Routine serologic testing and diagnosis.
AB  - Hepatitis C, which is caused by the hepatitis C virus (HCV), is a major public
      health problem in the United States. HCV is most efficiently transmitted through
      large or repeated percutaneous exposures to blood. Most patients with acute HCV
      infection develop persistent infection, and 70 percent of patients develop
      chronic hepatitis. HCV-associated chronic liver disease results in 8,000 to
      10,000 deaths per year, and the annual costs of acute and chronic hepatitis C
      exceed $600 million. An estimated 3.9 million Americans are currently infected
      with HCV, but most of these persons are asymptomatic and do not know they are
      infected. To identify them, primary health care professionals should obtain a
      history of high-risk practices associated with the transmission of HCV and other
      bloodborne pathogens from all patients. Routine testing is currently recommended
      only in patients who are most likely to be infected with HCV.

PMID- 9917577
TI  - Screening for genetic risk of breast cancer.
AB  - Approximately 10 to 15 percent of all breast cancers are thought to be familial
      and about one third of these cases are due to an inherited mutation in a BRCA1 or
      BRCA2 breast cancer-susceptibility gene. The lifetime incidence of breast cancer
      in mutation carriers is above 50 percent, and carriers of BRCA1 mutation also
      have a substantially increased risk of ovarian cancer. BRCA1 and 2 mutations are
      associated with early-onset breast cancer, and some experts call for aggressive
      screening of affected persons. Monthly self-examination of the breasts beginning
      at age 18 and annual clinical examinations and mammography after age 25 have been
      recommended but are of unproven benefit. Prophylactic mastectomy and oophorectomy
      have been advocated by some authorities, but these interventions are disfiguring
      and for some carriers of the gene, they are unnecessary. The patient's decision
      to undergo genetic screening is complicated by the technical difficulty of the
      test, the substantial cost and the still incomplete understanding of the
      penetrance of disease in known mutation carriers.

PMID- 9917578
TI  - Poliovirus vaccine options.
AB  - As a result of the success of immunization, indigenous wild poliomyelitis has
      disappeared from the United States. Of 142 confirmed cases of paralytic
      poliomyelitis reported in the United States from 1980 to 1996, 134 were
      classified as vaccine-associated paralytic poliomyelitis (VAPP). Persons with
      VAPP have a disabling illness, and this has caught the attention of the lay
      media. The risk of VAPP is one case per 750,000 doses distributed for the first
      dose of oral poliovirus vaccine (OPV) and one case per 2.4 million doses of OPV
      distributed overall. Because of this risk, most parents prefer a vaccine schedule
      that starts with inactivated poliovirus vaccine (IPV), even though extra
      injections are required. IPV does not cause VAPP. New studies show that high
      immunization rates can be achieved in disadvantaged populations with a schedule
      starting with IPV. The American Academy of Family Physicians now recommends that
      the first two doses of poliovirus vaccine should be IPV; that is, either an all
      IPV schedule or a sequential schedule of two doses of IPV followed by two doses
      of OPV. OPV is no longer recommended for the first two doses and is acceptable
      only under special circumstances, such as when parents do not accept the
      recommended number of injections.

PMID- 9917579
TI  - Snowboarding injuries.
AB  - Snowboarding is a popular winter sport that involves riding a single board down a
      ski slope or on a half-pipe snow ramp. Compared with injuries resulting from
      traditional alpine skiing, snowboarding injuries occur more frequently in the
      upper extremities and ankles and less frequently in the knees. Different types of
      snowboard equipment, rider stance and snowboarding activity tend to result in
      different types of injury. Snowboarder's ankle, a fracture of the lateral talus,
      must be considered in a snowboarder with a "severe ankle sprain" that has not
      responded to treatment. Risk of injury may be lowered by using protective
      equipment, such as a helmet and wrist guards.

PMID- 9917580
TI  - Surgical options in the management of groin hernias.
AB  - Inguinal and femoral hernias are the most common conditions for which primary
      care physicians refer patients for surgical management. Hernias usually present
      as swelling accompanied by pain or a dragging sensation in the groin. Most
      hernias can be diagnosed based on the history and clinical examination, but
      ultrasonography may be useful in differentiating a hernia from other causes of
      groin swelling. Surgical repair is usually advised because of the danger of
      incarceration and strangulation, particularly with femoral hernias. Three major
      types of open repair are currently used, and laparoscopic techniques are also
      employed. The choice of technique depends on several factors, including the type
      of hernia, anesthetic considerations, cost, period of postoperative disability
      and the surgeon's expertise. Following initial herniorrhaphy, complication and
      recurrence rates are generally low. Laparoscopic techniques make it possible for
      patients to return to normal activities more quickly, but they are more costly
      than open procedures. In addition, they require general anesthesia, and the long
      term hernia recurrence rate with these procedures is unknown.

PMID- 9917581
TI  - Mirtazapine: a newer antidepressant.
AB  - Mirtazapine is a newer antidepressant that exhibits both noradrenergic and
      serotonergic activity. It is at least as effective as the older antidepressants
      for treating mild to severe depression. Sedation is the most common side effect.
      Although agranulocytosis is the most serious side effect, it is rare
      (approximately one in 1,000) and usually reversible when the medication is
      stopped. Mirtazapine is relatively safe in overdose. Many clinicians consider
      mirtazapine a second-line or even third-line antidepressant to be used when older
      antidepressants are not tolerated or are ineffective. Physicians who are
      concerned about the risks of elevated lipid levels and agranulocytosis may choose
      to reserve mirtazapine as a third-line choice. It is particularly useful in
      patients who experience sexual side effects from other antidepressants.
      Mirtazapine is also a good choice in depressed patients with significant anxiety
      or insomnia. Although mirtazapine has been used successfully in Europe for a
      number of years, its place in the care of patients with depression in the United
      States has not yet been established.

PMID- 9917582
TI  - Photo Quiz. A spot in the eye.

PMID- 9917583
TI  - Epilepsy, driving and the law.

PMID- 9917584
TI  - The 1999 harmonized immunization schedule.

PMID- 9917585
TI  - 'Don't scream, Miss Annie. Don't scream.'.

PMID- 9917586
TI  - Trendelenburg's test: 1895.

PMID- 9917587
TI  - The Otto Aufranc Award. Image guided navigation system to measure
      intraoperatively acetabular implant alignment.
AB  - There has been little clinical research to examine the effects of patient
      positioning and pelvic motion on the alignment of the acetabular implant during
      total hip replacement surgery. Until now, no tools were capable of accurately
      measuring these variables during the actual procedure. As part of a broader
      program in medical robotics and computer assisted surgery, a clinical system has
      been developed that includes several enabling technologies. The hip navigation
      system (HipNav) continuously and precisely measures pelvic location and tracks
      relative implant alignment intraoperatively. HipNav technology is used to gauge
      current clinical practice and provide intraoperative feedback to surgeons with
      the goal of improving the precision and accuracy of acetabular alignment during
      total hip replacement. This system provides surgeons with a new class of image
      guided measurement tools and assist devices. These tools successfully were
      introduced into the clinical practice of surgery with results showing the
      following: (1) There exist unpredictable and large variations in the initial
      position of patients' pelves on the operating room table and significant pelvic
      movement during surgery and during intraoperative range of motion testing; (2)
      current mechanical acetabular alignment guides do not account for these
      variations, and result in variable and in the majority of cases unacceptable
      acetabular alignment; and (3) press fitting oversized acetabular components
      influences the final cup orientation.

PMID- 9917588
TI  - The John Charnley Award. Prophylaxis of fat and bone marrow embolism in cemented
      total hip arthroplasty.
AB  - The efficiency of a new cementing technique developed to prevent the risk of
      intraoperative pulmonary embolism was assessed. Seventy patients with
      coxarthrosis entered into a prospective, randomized clinical trial. In the
      control group of 35 cases the total hip replacement was cemented conventionally.
      In the second group a proximal drainage placed along the Linea aspera, and a
      distal drainage placed in the diaphysis, created a vacuum in the medullary cavity
      of the femur during the insertion of the stem. The operation was performed with
      the patient under blood gas analysis and hemodynamic and transesophageal
      echocardiography monitoring. Severe transatrial embolic events were observed
      during the insertion of the femoral component in 94% of the cases of the control
      group and in 14% of the cases of the vacuum group; the difference is
      statistically significant. A significant decrease of arterial partial pressure of
      O2 (-40.8 mm Hg) and increase of the pulmonary shunt values (+28.3%) occurred 5
      minutes after the observation of embolic events in the cases operated on
      conventionally, but these parameters showed minimal changes in the vacuum group.
      The rise of intramedullary pressure in the femur is the most decisive pathogenic
      factor of pulmonary embolism during total hip arthroplasty. The logical
      prophylactic measure to prevent intravasation of fat and bone marrow is to create
      sufficient drainage. The cohorted investigation showed the value of the vacuum
      cementing technique for a substantial reduction of intraoperative embolism and
      pulmonary impairment.

PMID- 9917589
TI  - The Frank Stinchfield Award. Inhibition of heterotopic ossification with
      radiation therapy in an animal model.
AB  - An animal model for the study of heterotopic ossification was developed and the
      effects of perioperative radiation were analyzed. In Phase I, New Zealand White
      rabbits (n = 18) underwent surgery either with or without muscle injury on each
      hip to establish the most reliable model in which to study heterotopic
      ossification. In Phase II, rabbits (n = 36) underwent either 400, 800, or 1200
      cGy radiation to one hip 24 hours after bilateral hip surgery to establish a dose
      response relationship for postoperative radiation therapy. In Phase III, rabbits
      (n = 24) underwent preoperative radiation therapy (800 cGy) at 4, 16, or 24 hours
      preoperatively to investigate the mechanism of action and efficacy of
      preoperative radiation therapy. Monthly radiographs were graded by blinded
      observers for severity of heterotopic ossification. Mean grade, intraobserver and
      interobserver variability, and statistical significance were evaluated. In Phase
      II, 17 of 18 rabbits generated heterotopic ossification in both hips, and the
      mean grade of heterotopic ossification was always greater on the operative side
      with intentional muscle injury. Variability in the grading was considered
      excellent. Phase II revealed that 800 cGy was the minimal effective dose.
      Contrary to hypothesis, Phase III revealed an increasing grade of heterotopic
      ossification coinciding with a decreasing preoperative time interval, with the
      difference in heterotopic ossification grade with 24-hour versus 4-hour
      preoperative radiation being significant. The rabbit model is reliable and
      reproducible and closely resembles the human clinical situation after hip
      surgery. Preoperative and postoperative radiation effectively prevented
      heterotopic ossification formation. The results support the use of preoperative
      radiation and establish a need for additional investigation regarding the
      mechanism of action and timing of preoperative radiation therapy.

PMID- 9917590
TI  - Effects of design changes on cemented tapered femoral stem fixation.
AB  - The effects of matte finish and modularity on loosening of tapered stems using
      the same cementing technique were studied prospectively. In 80 patients, 82
      cemented Exeter primary stems were implanted at total hip revision by one surgeon
      using the same surgical and cementing technique throughout the series. The
      polished stems behaved differently than the matte surfaced stems behaved.
      Polished stems subsided in the cement mantle an average of 1 mm at 2 years after
      implantation, but without subsequent loosening of stems at as long as 12 years
      after implantation. Matte surfaced stems with metal centralizers had a higher
      loosening rate, and loss of fixation at the prosthesis to cement interface was
      identified as an early sign of loosening of these stems. At a mean 6-year
      followup, there were no revisions nor was there radiographic evidence of
      loosening of the polished modular stems. It is concluded that matte finish
      results in increased loosening of tapered stems but the introduction of
      modularity did not.

PMID- 9917591
TI  - Cemented femoral stem performance. Effects of proximal bonding, geometry, and
      neck length.
AB  - The effects of proximal bonding, distal stem geometry, and femoral neck length on
      cement and interface stresses were determined to understand better their role in
      clinical performance. The effects of stem design were compared with the effects
      of environmental variables, patient weight, and patient activity. Finite element
      models were used to determine peak cement and interface stresses, and an
      experimental layout was used to separate design and environmental effects.
      Bonding reduced cement mantle stresses by 35% to 60%, to levels below the cement
      fatigue strength. A flat sided implant provided more torsional resistance,
      reducing shear stresses at the proximal cement-prosthesis interface by 22% to 73%
      with respect to a distal round implant. Neck length had minimal effects on
      stresses compared with bonding or implant geometry. Cement-bone interface
      stresses were more sensitive to patient activity than to the design variables.
      Therefore, claims that a strong cement and prosthesis bond may be harmful to the
      bone-cement interface are unjustified based on these results. The best
      combination of design variables was a proximally bonded, flat sided implant with
      neck length left to the surgeon's discretion. This combination was most effective
      at protecting the cement mantle and prosthesis interface and perhaps the cement
      bone interface by minimizing stresses associated with cement debris generation.

PMID- 9917592
TI  - Importance of a thin cement mantle. Autopsy studies of eight hips.
AB  - The question whether thin cement mantles around cemented femoral components led
      to an increased frequency of cracks in the cement was asked. Microscopically,
      multiple cross sections of eight femurs retrieved at autopsy from clinically
      successful total hip replacements after prolonged in vivo service containing well
      fixed Harris Design 2 cemented femoral components were studied. None of the
      components were loose by radiographic criteria. All were fixed solidly when
      loaded in vitro in simulated stair climbing and gait, as assessed by high
      resolution micromotion sensors. The specimens were sectioned transversely at 5-mm
      increments. The cross sections were examined under a dissecting microscope at x
      100. A thin mantle arbitrarily was defined as a mantle of less than 1 mm in
      thickness. The analysis of the contact radiographs showed that the routine
      anteroposterior and lateral radiographs underestimated the prevalence of thin
      cement mantles and mantle defects. Although overall on all the cross sections 9%
      of the aggregated cement mantles was classified as having thin cement, 92 of the
      101 cement cracks occurred in areas of the mantles that were less than 1 mm
      thick.

PMID- 9917593
TI  - Pressurization and centralization enhance the quality and reproducibility of
      cement mantles.
AB  - Cementing technique has a profound influence on the incidence of aseptic
      loosening of total hip replacements. Two specific measures that seem to have the
      greatest impact on the longevity of cemented femoral stems are pressurization of
      cement and control of mantle thickness, typically through the use of modular
      centralizing devices attached to the tip of the prosthesis. Two laboratory
      studies are presented that examine the success of these measures in clinical
      practice. In the first study, the performance of five designs of intramedullary
      plugs in resisting migration during pressurization of cement was evaluated in
      human anatomic specimen femurs. Profound differences were observed between the
      performance of the different plug designs. In canals larger than 12 to 14 mm,
      most commercial devices failed to resist pressures greater than 30 to 40 pounds
      per square inch. Overall, it was estimated that between 6% to 76% of these
      devices would fail to resist cement pressures of 50 pounds per square inch in
      clinical practice. The second study examined the role of distal centralizers in
      the accumulation of air bubbles around the distal tip of the prosthesis during
      insertion of the stem into the femur. Acrylic replicas of a femoral stem were
      implanted in cavities simulating the femoral canal. Colored dyes, present within
      the cement, revealed the complex patterns of cement flow. It was shown that
      cement, dragged from the top of the femur, forms a thin layer that covers the
      entire surface of the prosthesis and the distal centralizer. Significant voids
      were present behind the trailing edges of the distal centralizer in 42% of the
      cases examined. These studies show that improvements in intramedullary plugs and
      stem centralizers are needed to increase the reproducibility of cement technique
      in total hip replacement.

PMID- 9917594
TI  - Cemented femoral component surface finish mechanics.
AB  - A cemented femoral component's surface finish may influence implant function
      through variations in cement adhesion and abrasion properties. Morphologic
      characterization of historic and current femoral hip prosthesis surface finishes
      show greater than x 20 range in implant roughness. Early implants typically had
      relatively smooth surfaces, whereas many of the more recent implants have rougher
      surface finishes. Smoother implant surfaces have lower cement-metal interface
      fixation strength, whereas rougher surfaces have greater fixation strength. With
      interface motion, the smoother surfaces are less abrasive of bone cement, whereas
      rougher implant surfaces are more abrasive. Because of enhanced bone cement
      attachment, rougher implant surfaces may have a lower probability of interface
      motion, while at the same time, a higher debris generation consequence if motion
      occurs. In contrast, smoother implant surfaces may have a higher probability of
      interface motion with a lower debris generating consequence of that motion. The
      prolonged use of cemented total hip replacement may be approached by either
      extending the duration of implant function after cement-metal interface loosening
      with smooth surfaced implants or, in contrast, by extending the duration of
      cement-metal interface adhesion with rougher surfaced implants.

PMID- 9917595
TI  - Migration, stem shape, and surface finish in cemented total hip arthroplasty.
AB  - In many recent publications it was suggested that the amount of early subsidence
      of a femoral stem in total hip arthroplasty is indicative for later revision. In
      this article it is argued that stems can be designed according to alternative
      objectives, resulting in different shapes and surface roughness, each producing
      its own characteristic postoperative subsidence pattern. It was investigated
      whether these inherent subsidence patterns can be estimated in preclinical
      testing. For that purpose two stems, both without a collar, relying on cement
      fixation only, were compared regarding their stress transfer, migration, and
      induced micromotion behavior. Finite element analysis, cyclic bench testing of
      substitute bone reconstructions, and clinical radiostereophotogrammetric analysis
      were applied. The stems investigated were the Exeter, which is assumed to be a
      force closed fixation design, relying on subsidence under load as a method of
      maintaining stability, and the SHP, as a shape closed fixation design, meant to
      be contained by the cement mantle. Both designs were true to their design
      concepts in the analyses, in the sense that migrations and micromotions of the
      Exeter stems far exceeded those of the SHP stems. It was found that preclinical
      studies such as finite element analysis or bench tests give reasonable
      indications of in vivo postoperative behavior. It is concluded that early
      clinical migration values should be considered relative to stem shape and surface
      finish, when prediction of later revision probability is the issue.

PMID- 9917596
TI  - Loosening rates and bone lysis with rough finished and polished stems.
AB  - In the senior author's 27-year experience in cementing femoral components, stems
      with smooth and rough surfaces were implanted. Prospective data have been kept on
      all patients allowing extensive long term followup. The polished Charnley stem
      was implanted in 168 hips from 1971 to 1975. To date, only four (2.4%) stems have
      required revision for aseptic loosening and four others for fracture. None showed
      significant bone lysis. The experience with the T-28 and TR-28 allows comparison
      of stems of similar geometry, but with different surface finishes. From 1972 to
      1977, 209 polished T-28 stems were inserted and to date 18 (14 for fracture and
      four for loosening, 1.9%) have required revision. None had associated bone lysis.
      From 1977 to 1982, 227 second generation TR-28 matte surface finish stems (Ra 30)
      were implanted. Five required revision, three (2.2%) with major bone lysis.
      Radiographic review revealed minimal lysis in four (1.9%) polished T-28 stems and
      in 11 (4.9%) TR-28 stems, three of which showed major bone destruction. From 1980
      to 1993, 1061 Iowa stems were implanted. In 1986 proximal precoat was added,
      which required additional roughening of the surface. In 1995 a 1.5% early
      loosening rate was reported with significant bone lysis, complicating revision.
      By 1998 34 (3.2%) stems have required revision, all associated with significant
      bone loss. Revision of one of 12 original Iowa (Ra 30) and 12 of 22 (Ra 80) grit
      blasted stems was needed before 5 years postoperatively. These early failures
      prompted the author to return to a polished stem with a geometry almost identical
      to the Charnley stem.

PMID- 9917597
TI  - Failure of total hip arthroplasty with a precoated prosthesis. 4- to 11-year
      results.
AB  - A series of early femoral component failures prompted a detailed retrospective
      clinical and radiographic review of 176 hybrid cemented total hip arthroplasties
      using a polymethyl-methacrylate coated femoral prosthesis. All surgeries were
      performed using third generation cement techniques. Average length of followup
      was 6.3 years (range, 3-12 years). Twenty-one patients died, and one underwent
      revision surgery because of sepsis. Of the remaining 154 total hip
      arthroplasties, 23 (15%) of the femoral components failed (21 revised, two
      definitely loose). The average time to revision was 3.9 years. None of the
      acetabular components failed. Comparison between the failure and nonfailure
      groups revealed that poor cement mantles (Grades C or D) with distal cement
      mantle deficiencies were statistically significant predictors of femoral failure.
      The most common mechanism of failure was progressive, circumferential cement-bone
      interface osteolysis with relative preservation of the cement-metal interface.
      Debonding of the cement column from the prosthesis was a late finding and
      occurred in only 45% of failed cases. Incorporating the techniques of
      centralization and centrifugation significantly improved clinical results.
      Strengthening of the cement-prosthesis interface may magnify the deleterious
      effects of a poor cement mantle and predisposes the cement-bone interface to
      failure.

PMID- 9917599
TI  - Causes of and treatment protocol for instability of total hip replacement.
AB  - Dislocation of the total hip replacement is a devastating complication,
      physically and mentally. It was determined whether there are radiographic or
      operative findings predictive of repeat dislocation and whether there are causes
      of dislocation that require immediate reoperation. A previously published
      classification of dislocations was used which evaluates (1) positional (no
      radiographic abnormality); (2) component malposition (femur or acetabulum), which
      is inadequate version or position of the acetabular or femoral component; (3)
      soft tissue imbalance (change in the length or displacement of the hip), which is
      a change in the muscle functional length of the hip; and (4) component
      malposition and soft tissue imbalance. Categories of treatment of dislocations
      were established that could be correlated to the cause of the dislocation: (1)
      Category I is a successful closed reduction; (2) Category II is a successful
      reoperation; (3) Category III is a reoperation with subsequent repeat
      dislocations successfully treated with closed reduction; and (4) Category IV is
      comprised of hips that require multiple reoperations for treatment of
      dislocations. The results are that any dislocation of any origin may be treated
      successfully with closed reduction so that this should be the first choice of
      treatment. To avoid multiple treatments, immediate reoperation should be
      performed if the hip is unstable when the patient is examined under anesthesia
      after the closed reduction. Hips with soft tissue imbalance and weakness of the
      abductor musculature, with or without component malposition, are most at risk for
      multiple operations. These hips may be considered for mechanical stability
      (constraint in the acetabular replacement) at reoperation.

PMID- 9917598
TI  - Long-term results of cemented femoral stems with roughened precoated surfaces.
AB  - Several recent articles have raised the question that rough surfaces with or
      without precoating may contribute to the loosening of cemented femoral stems. In
      this article the author collates selected reports of several different cemented
      femoral stem designs that have rough surfaces which have shown excellent long
      term results. Femoral stem loosening is generally multifactorial. It often is
      difficult to separate the effect of stem design or other changes from the effect
      of surface finish. Many rough surfaced cemented femoral stems have served well
      for decades. It is important to analyze all the pertinent factors in cases of
      early loosening.

PMID- 9917600
TI  - A finite element analysis of factors influencing total hip dislocation.
AB  - A previously validated three-dimensional finite element model was used to study
      how several total hip component design and surgical placement variables
      contribute to resisting the propensity for posterior dislocation in the case of
      leg crossing in an erectly seated position. The computational formulation
      incorporated treatments of polyethylene material nonlinearity and large
      displacement sliding contact. The primary outcome measures were the peak
      intrinsic moment developed to resist dislocation, and the ranges of motion before
      neck on lip impingement and before frank dislocation. Modifications of the
      acetabular linear design (chamfer bevel angle, lip breadth, head center inset)
      involved trading off improved peak resisting moment for compromised range of
      motion and vice versa. Increases of head size led to substantial improvements in
      peak resisting moment, but if the head to neck diameter ratio was held constant,
      had almost no influence on the component range of motion. For the leg crossing
      event studied, increased component anteversion, and even more so increased tilt
      (less net abduction), achieved improvements in range of motion and in peak
      resisting moment, but these changes imply diminished resistance to anterior
      dislocation from extension and adduction motion inputs.

PMID- 9917601
TI  - Relationship of femoral head and acetabular size to the prevalence of
      dislocation.
AB  - Two clinical studies, one prospective randomized and one retrospective, were
      performed to evaluate the relationship of femoral head size and acetabular
      component outer diameter to the prevalence of dislocation of the modular total
      hip replacement. Between October 1995 and April 1996, 31 primary total hip
      arthroplasties in 30 patients were randomized to a femoral head diameter of 22 mm
      or 28 mm, for two groups of acetabular components of outer diameters of 56 mm or
      larger and 54 mm or smaller. Head size (22 mm) and acetabular component outer
      diameter (> or = 56 mm) were found to increase the risk of dislocation. From
      December 1984 to January 1994, 308 primary total hip arthroplasties were
      performed through a posterior approach by one surgeon using a modular 28 mm
      femoral head and one type of uncemented acetabular component. The rate of
      dislocation for acetabular components with an outer diameter of 62 mm or larger
      was increased significantly (five of 36 hips, 14%) compared with those with an
      outer diameter of 60 mm or smaller (11 of 272 hips, 4%).

PMID- 9917602
TI  - Salvage of total hip instability with a constrained acetabular component.
AB  - Between April 1988 and February 1993, 101 constraining acetabular components were
      implanted into 98 patients. One patient was lost to followup at 8 months.
      Otherwise, all patients were observed until death or for at least 2 years minimum
      followup. The average clinical followup for the living patients was 61 months
      (range, 24-97 months). Indications for the use of the constrained acetabular
      components were recurrent dislocation (an average of six dislocations, range 2
      20) in 56 cases, intraoperative instability in 38 cases, and neurologic
      impairment in seven cases. For the entire group there were four cases of
      recurrent dislocation or failure of the component (4%). For the cases where this
      component was used for recurrent dislocation, 96% (54 of 56 cases) had no
      additional dislocations. Radiographically, at this short term followup, there was
      no evidence of an increased incidence of femoral or acetabular component
      loosening. The authors recommend judicious use of this component as a salvage
      measure for desperate cases of hip instability during or after total hip
      arthroplasty.

PMID- 9917603
TI  - Total hip arthroplasty. Concerns with extensively porous coated femoral
      components.
AB  - A series of 507 consecutive, unselected cementless hip arthroplasties performed
      by one surgeon was reviewed to address specifically potential concerns with the
      use of extensively coated femoral components, including the frequency and nature
      of reoperation, thigh pain, component stability, osteolysis, and stress
      shielding. Excluding hips in patients who had died or were lost to followup,
      there were 426 hips with minimum 5-year followup. The overall femoral reoperation
      rate of 2.6% (13 cases) included seven for failure of fixation and six for
      osteolysis. Of the unrevised cases, 96% of the femoral components showed
      radiographic bone ingrowth, and 3.7% showed a stable fibrous pattern. Fixation
      did not deteriorate with time. A 2.9% incidence of activity limiting thigh pain
      did affect clinical outcome (limp, ambulation tolerance, support), but there were
      no clinical or radiographic predisposing variables. There was no detectable
      femoral osteolysis in 88.3% of cases. The remainder had lesions confined to Gruen
      Zones 1 and 7, suggesting that circumferential extensive coating was protective
      against distal osteolysis. Although osteolysis did not affect component
      stability, in six cases it did result in pathologic trochanteric fracture,
      contributing to the frequency of reoperation. Stress shielding was common (25%)
      and was related to older patients and the use of larger diameter stems (> 15 mm),
      but did not predispose to thigh pain, loosening, osteolysis, or an inferior
      clinical result. These results documented the clinical and radiographic success
      in the use of extensively coated cementless femoral components. Debris generation
      from wear and resulting osteolysis remain significant concerns in a hip
      arthroplasty with this design as with many others. However, concerns about the
      high incidence of reoperation, thigh pain, component instability, or stress
      shielding are not supported by this study.

PMID- 9917604
TI  - Cementless femoral design concerns. Rationale for extensive porous coating.
AB  - In the early 1980s increased interest in proximally porous coated stems was
      sparked by first generation cemented stem failures in young patients and concerns
      with extensively porous coated cementless stems regarding thigh pain and stress
      shielding. As a result, various proximally porous coated stems were produced,
      each with differing clinical results. Using 5-year minimal followup as a cut off,
      the evolution of proximally porous coated stems during the years is presented and
      compared with the long term results obtained with extensively porous coated
      stems. Problems with some of the early proximally coated designs have been
      reported in the literature. Despite subsequent design modifications, the modern
      proximally coated stem has not eliminated thigh pain or stress shielding.
      Although some of the proximally porous coated stems have had good results, the
      question whether the push for proximally coated femoral stems resulted in
      significant clinical improvement versus the long term results of extensively
      porous coated stems remains.

PMID- 9917605
TI  - Hydroxyapatite in total hip arthroplasty. Clinical results and critical issues.
AB  - Surgeons who perform arthroplasties have posed some critical questions about
      hydroxyapatite. Does hydroxyapatite coating enhance bone ingrowth or ongrowth?
      Will hydroxyapatite lead to increased polyethylene wear or an increased incidence
      of osteolysis? Will the hydroxyapatite coating disappear, and if so, what will be
      left to maintain implant fixation? A multicenter study of 316 hips (282 patients)
      with a proximally hydroxyapatite coated stem and either a hydroxyapatite or
      porous coated cup were followed up 8.1 years (range, 5.6-9.9 years). The average
      patient age was 50 years (range, 16-81 years), and 61% of the patients were male.
      One (0.3%) stem, three (2.7%) porous coated cups, and 25 (11.9%) hydroxyapatite
      coated cups were revised for aseptic loosening. Disappointing results on the
      acetabular side indicate that substrate design is critical. There were no cases
      of intramedullary femoral osteolysis, and the incidence of acetabular and
      proximal femoral osteolysis- and polyethylene wear was no greater than that seen
      with other cementless or cemented components. Based on these clinical results and
      a critical review of the literature, it is concluded that hydroxyapatite coated
      hip components do enhance ingrowth or ongrowth with no increased incidence of
      osteolysis for as many as 10 years. Concern about the disappearance of the
      hydroxyapatite coating with time seems moot in light of the above clinical
      findings.

PMID- 9917606
TI  - A critical look at cementless stems. Taper designs and when to use alternatives.
AB  - The clinical and radiographic efficacy of cementless taper design femoral
      components in total hip arthroplasty was determined. Cementless, taper design,
      femoral components have been shown to offer comparable clinical results to
      cemented femoral implants in a double blind, randomized, clinical trial. No
      differences were observed in terms of disease specific, patient specific, global
      health, functional capacity, or cost to utility outcome measures. The prevalence
      of pain in the thigh was the same in each group. Fixation of cementless, taper
      design, femoral stems depended on three-point fixation as shown on lateral
      radiographs. A clinical algorithm for femoral stem selection, based on more than
      10 years experience with more than 1000 cementless, taper design femoral stems
      has been developed. Cementless, taper design, femoral implants currently are used
      in 75% of the authors' patients, provided they are younger than 75 years of age
      and have funnel shaped proximal femoral medullary canals. Cemented femoral stems
      are used in older patients, those who have cylindric medullary canals, and those
      who have inflammatory or unusual bone diseases (Paget's disease, previously
      irradiated bone).

PMID- 9917607
TI  - Posterior approach to total hip replacement using enhanced posterior soft tissue
      repair.
AB  - The two senior authors (PMP, RP) independently began using an identical enhanced
      posterior soft tissue repair after total hip replacement through a posterior
      approach. In the first author's experience, a dislocation rate of 4% in 395
      patients before using the enhanced closure was reduced to 0% in 395 patients in
      whom the enhanced closure was performed. In the second author's experience, 160
      total hip replacements had a dislocation rate of 6.2% before the enhanced closure
      whereas 124 total hip replacements had a dislocation rate of 0.8% after the
      enhanced closure. These results are highly statistically significant.

PMID- 9917608
TI  - Radiographic and histologic analysis of cemented double tapered femoral stems.
AB  - The macroscopic, radiographic, and histologic features of the prosthesis-cement
      and cementbone interfaces and adjacent bone were studied in 21 cemented
      hemiarthroplasties in sheep that had lived until sacrifice at 9 months. The
      features were compared with those immediately after implantation of the stem in
      the contralateral femur. The femoral stem was a double taper that was either
      polished collarless, matte collarless, or matte collared. There was no prosthesis
      to cement debonding or cement to bone radiolucent line immediately after
      implantation, and there was excellent interdigitation at the cement-bone
      interface. After 9 months there was no evidence of prosthesis to cement debonding
      and no stem with definite loosening. At 9 months after implantation there was
      evidence of bone remodeling with new bone filling what were presumed to be gaps
      at the cement-bone interface from immediately after implantation. Radiolucent
      lines at the cement-bone interface were found to represent trabeculation of the
      cortical bone rather than the presence of a complete fibrous interface, which was
      not seen. There was no difference between stem types. Sheep have been shown to be
      useful in a model of cemented hip arthroplasty and, although no differences were
      seen between stem types at 9 months after implantation, long term differences
      cannot be excluded.

PMID- 9917609
TI  - Effect of increasing temperature on the properties of four bone cements.
AB  - This investigation uses a laboratory model to evaluate the effects of a heated
      femoral stem on the biomechanical properties of four common acrylic bone cements.
      American Society for Testing Materials dog bone shaped acrylic cement specimens
      made at four test temperatures, 0 degree C, 23 degrees C, 37 degrees C and 50
      degrees C, were tested for modulus, ultimate tensile strength, fracture
      toughness, and percent porosity. Fatigue strength was tested in Simplex P at 23
      degrees C and 37 degrees C. The data allow direct comparison among four cement
      brands at each of the four temperature conditions. No adverse changes of the
      mechanical properties were found for any cement at any temperature. Modulus,
      fracture toughness, and fatigue strength were unaffected by increased
      temperature. Ultimate tensile strength increased in Simplex P and Zimmer
      Osteobond but was unaffected for Zimmer Regular and Palacos R cements. Percent
      porosity was related to temperature changes inversely in all brands studied,
      except for Palacos R which consistently had low porosity, unaffected by
      temperature variation. Fatigue strength of Simplex P was unaffected by heating to
      37 degrees C. Based on this laboratory model, heating of the femoral stem could
      save time without sacrificing mechanical properties of acrylic bone cement.

PMID- 9917610
TI  - Porosity reduction in acrylic cement is clinically irrelevant.
AB  - Evidence from studies on migration raises serious doubts regarding the part
      played by fatigue failure of acrylic bone cement in the genesis of aseptic
      loosening of the components of total hip arthroplasties. Moreover, the
      viscoelastic properties of cement raise serious doubts concerning the relevance
      of conventional laboratory fatigue studies to the in vivo behavior of acrylic
      cement. It is not surprising that there is considerable clinical evidence that
      reduction of porosity in acrylic cement is of no relevance to the long term
      outcomes of total hip arthroplasty. These matters remain controversial, and
      randomized prospective trials would be necessary to settle the issues. For
      various reasons, such trials are unlikely to be performed.

PMID- 9917611
TI  - Osteonecrosis of the humeral head treated by core decompression.
AB  - Core decompression is one treatment used for symptomatic osteonecrosis of the
      humeral head. The purpose of this report was to examine the long term outcome of
      this procedure. Sixty-three shoulders in 43 patients who underwent a core
      decompression for humeral head osteonecrosis were followed up from 2 to 20 years
      (mean, 10 years). None of these patients had responded to nonoperative treatment
      before core decompression. Results of core decompression according to
      preoperative Ficat and Arlet stage revealed Stage I disease had 15 of 16 (94%)
      successful outcomes and Stage II had 15 of 17 (88%) successful outcomes. Stage
      III had 16 of 23 (70%) successful results and Stage IV had one of seven (14%)
      successful result. Core decompression of the shoulder is a safe procedure with
      few recognized complications and can be performed on an outpatient basis. The
      procedure has been successful for Stages I, II, and III osteonecrosis in terms of
      early relief of pain and increased function.

PMID- 9917612
TI  - Idiopathic hip instability. An unrecognized cause of coxa saltans in the adult.
AB  - The painful, snapping hip often presents a diagnostic dilemma having many
      potential etiologies. An understanding of the precise cause increases the
      potential for successful treatment. Five patients with no prior history of
      significant trauma were evaluated, all of whom had longstanding painful snapping
      in the groin and consistent symptoms of gait disturbance and increased pain in
      the provocative position of hip flexion, adduction, and internal rotation.
      Multiple prior tests and procedures had been nondiagnostic. Simple manual
      longitudinal traction under fluoroscopy showed subluxation with appearance of a
      vacuum sign in the symptomatic hip, whereas no such finding was observed on the
      asymptomatic side. This strongly suggests atraumatic hip instability as a
      previously unrecognized cause of the painful, snapping hip. The easily obtainable
      diagnostic traction radiograph is described.

PMID- 9917613
TI  - Metastatic carcinoma to skeletal muscle. A report of 15 patients.
AB  - The records of 15 patients with metastatic carcinoma to skeletal muscle treated
      between 1979 and the present were reviewed. Fourteen patients were referred with
      a diagnosis of soft tissue sarcoma and one with suspected infection. There was a
      previous diagnosis of carcinoma in eight patients but seven patients had no prior
      diagnosis of a known malignancy. Primary tumors were lung (eight), melanoma
      (two), gastrointestinal (one), kidney (one), and bladder (one). No primary tumor
      could be identified in two patients. Local control of metastatic lesions was
      achieved by radiotherapy in 11 patients as an initial measure. Two patients
      underwent wide excision and one declined treatment for local tumor control. Eight
      patients died within 12 months of presentation and survival analysis indicated a
      25% overall survival at 60 months. Two patients remained free of disease at 132
      months and 72 months. From this study and a review of 52 cases reported in the
      literature, the authors are unable to find any clinical or radiographic
      characteristics that distinguish metastatic carcinoma to muscle from soft tissue
      sarcomas. Surgical resection can be reserved for cases in which radiation does
      not provide local control.

PMID- 9917614
TI  - Gaining independence in tetraplegia. Cleveland technique.
AB  - Considerable independence can be achieved by four simple operations that can be
      done for patients with tetraplegia. Transfers for wrist extension were done 17
      times. Posterior deltoid transfers were done 59 times. Opponens transfers were
      done 112 times. Transfers for finger flexion were done 88 times. Opponens and
      finger flexion transfers should be done at the same time. There were 22 other
      operations done. The patients with C6, C7, and C8 complete neurologic motor
      levels were almost as independent after their tendon transfers as paraplegics.
      They could transfer from a chair, insert a catheter, write, type, hold a book,
      take care of their toilet needs, bathe themselves, eat food and drink, dress
      themselves, and perform other activities of daily living. The few patients with a
      C5 neurologic level that was surgically treated for wrist extension acquired
      automatic grasp or used a wrist driven splint. A posterior deltoid transfer was
      not done on any of the patients with a C5 neurologic level but it is recommended
      now.

PMID- 9917615
TI  - Osteoclasts and effects of interleukin 4 in development of chronic osteomyelitis.
AB  - The cellular response to trauma and infection was studied in a murine model of
      posttraumatic osteomyelitis. Osteoclast response differed markedly depending on
      whether infection with Staphylococcus aureus accompanied the bone trauma. In
      animals recovering from sterile trauma, osteoclastic activity that was limited to
      the damaged or dead bone fragments caused rapid elimination of all recognizable
      dead bone within 1 week. New bone was laid down in an orderly fashion. Animals
      with superimposed infection had an intense polymorphonuclear leukocyte response
      develop. Additionally, osteoclasts behaved as acute inflammatory responders with
      substantial activity at the margins of the infected site and at previously
      uninjured tibial cortex adjacent to the infection. Despite the exuberant
      osteoclast response, bony fragments were not resorbed (for at least 4 weeks after
      the trauma), that is, sequestra developed, and new bone was laid down over
      morphologically dead bone and on the cortex (involucrum). When the inhibitory
      cytokine, interleukin 4 was given in a single dose with the bacterial inoculum,
      the osteoclast response was moderated with almost complete elimination of
      osteoclast activity at normal tibial cortex adjacent to the infected site. The
      limitation of osteoclastic activity did not impair the host's containment of
      bacterial growth.

PMID- 9917616
TI  - Fixation of osteotomies using bioabsorbable screws in the canine femur.
AB  - The purpose of this study was to compare the healing properties of femoral
      osteotomies fixed by bioabsorbable screws (20:80 polyglycolic copolylactic acid
      copolymer) to standard stainless steel screws of a similar design in a dog
      femoral model. Two osteotomies were used, the trephine osteotomy (10 mm diameter)
      in the metaphyseal lateral femoral condyle and in the femoral diaphysis, and a
      unilateral osteotomy in the lateral femoral condyle. Two months after the
      trephine osteotomies, the femurs that contained the polymer screws were not
      significantly different in mechanical strength from the femurs treated with the
      stainless steel screws, either in the diaphyseal or metaphyseal model. There was
      no histological difference in bone healing between the metallic and polymer
      screws for all periods (2, 9, and 17 months). There was no adverse inflammatory
      response to the polymeric or metallic screws. By month 17, the polymer screws
      were resorbed completely. All the diaphyseal screw tracks had healed with bone
      and areas of remodeling were evident in two specimens. For the femoral condyle
      osteotomy model at 2 months, the polymer screws were present and intact, and all
      osteotomies healed with no evidence of inflammation. By 9 months, only one
      specimen had polymeric material left in the screw track. At 15 months, the screw
      tracks still were present but no evidence of any polymer remained. The tracks
      were filled with fibrous and adipose connective tissue. All osteotomies
      stabilized with either bioabsorbable polymer screws or stainless steel screws did
      heal satisfactorily without any complications, inflammation, or osteolysis. The
      polyglycolic polylactic acid copolymer may have a clinical role as a
      bioabsorbable material without the concerns for the osteolysis, foreign body
      reaction, and sterile abscess formation that have occurred with bioabsorbable
      fixation methods in the past.

PMID- 9917617
TI  - Polylactide pin with transforming growth factor beta 1 in delayed osteotomy
      fixation.
AB  - The effect of an absorbable pin containing transforming growth factor beta 1 on
      fracture healing was studied in a rat model of delayed osteotomy fixation.
      Transforming growth factor beta 1 was mixed into a blend of L-lactide oligomer
      and a copolymer of epsilon-caprolactone and DL-lactide that was placed in the
      grooves of a self reinforced fracture fixation pin made of poly-LD-lactic acid
      copolymer. A distal femoral osteotomy was made in 54 rats and left untreated. A
      week later surgery was performed to fix the osteotomy with a fracture fixation
      pin in 48 rats. In the remaining six rats no fixation was performed. The pin that
      was used in the study group contained either 5 micrograms (15 rats) or 50
      micrograms (15 rats) of the growth factor, while in the control group of 18 rats,
      an identical pin without growth factor was used. The femurs were examined
      radiographically, histologically, histomorphometrically, and
      microradiographically. Tetracycline labeling studies were used after a followup
      of 1, 3, and 6 weeks. Faster callus formation in the transforming growth factor
      beta 1 treated animals but no acceleration in the healing of the osteotomy is
      reported. The addition of bone growth factors to bioabsorbable fracture fixation
      materials may enhance bone healing.

PMID- 9917618
TI  - Shoulder mass in a 38-year-old woman.

PMID- 9917620
TI  - Significant advances have been made in the way surgeons treat fractures.

PMID- 9917619
TI  - Sclerosis and swelling of the clavicle in a 44-year old woman.

PMID- 9917621
TI  - A case of fracture of the Os Humeri, in which the broken ends of the bone not
      uniting in the usual manner, a cure was effected by means of a seton. 1803.

PMID- 9917622
TI  - The cell and molecular biology of fracture healing.
AB  - Fracture healing is a complex physiologic process that involves the coordinated
      participation of several cell types. By using a reproducible model of
      experimental fracture healing in the rat, it is possible to elucidate the
      integrated cellular responses that signal the pathways and the role of the
      extracellular matrix components in orchestrating the events of fracture healing.
      Histologic characterization of fracture healing shows that intramembranous
      ossification occurs under the periosteum within a few days after an injury.
      Events of endochondral ossification occur adjacent to the fracture site and span
      a period of up to 28 days. Remodeling of the woven bone formed by intramembranous
      and endochondral ossification proceeds for several weeks. Spatial and temporal
      expression of genes for major collagens (Types I and II), minor fibrillar
      collagens (Types IV and XI), and several extracellular matrix components
      (osteocalcin, osteonectin, osteopontin, fibronectin and CD44) are detected by in
      situ hybridization. Immunohistochemical studies show that expression of
      proliferating cell nuclear antigen is both time and space dependent and
      differentially expressed in the callus tissues formed by the intramembranous and
      endochondral processes. Chondrocytes involved in endochondral ossification
      undergo apoptosis (programmed cell death), and early events in fracture healing
      may be initiated by the expression of early response genes such as c-fos.
      Additional characterization and elucidation of fracture healing will lay the
      foundation for subsequent studies aimed at identifying mechanisms for enhancing
      skeletal repair.

PMID- 9917623
TI  - Concepts of fracture union, delayed union, and nonunion.
AB  - Laboratory and clinical scientists and practicing clinicians need definitions of
      union, delayed union, and nonunion. Fracture union is a gradual process, so
      quantitative measures are the most meaningful. However, end point definitions
      also are useful, but they need empirical validation. The measure that has
      received the best validation in human fractures is bending stiffness.
      Quantitative radiologic assessment of healing is difficult because varying
      patterns of bone bridging can occur, including periosteal, endosteal, and
      intercortical patterns. Natural fracture healing was studied in 43 cases of
      isolated, closed, conservatively treated tibial shaft fracture with serial
      measurements of bending stiffness and standard radiographs. Three healing groups
      were defined on the basis of stiffness recovery patterns. Four cases showed
      delayed union, defined as failure to reach a stiffness of 7 N-m per degree by 20
      weeks from fracture. The remaining cases had normal union, but at differing
      rates. Callus index was used as a measure of periosteal new bone formation.
      Stiffness measurements correlated more strongly than callus index with injury
      severity and functional outcome at 6 months. However, the callus index predicted
      behavior in those fractures that showed no tendency to heal at the 10-week stage.
      That is, absence of periosteal new bone in these cases presaged delayed union.
      These delayed union cases all eventually healed, still without producing
      periosteal callus, but other fractures in the series healed very rapidly, also
      without periosteal callus. The implication is that endosteal healing is capable
      of very rapid fracture bridging if conditions are right, but it also can occur
      late, after the periosteal healing response has ceased. These observations
      suggest a more rational approach to the definition of union, delayed union, and
      nonunion than that provided by the selection of arbitrary times. For
      conservatively treated fractures at least, delayed union can be defined as the
      cessation of the periosteal response before the fracture successfully has been
      bridged. Nonunion is the cessation of both the periosteal and endosteal healing
      responses without bridging.

PMID- 9917624
TI  - Pathophysiology of delayed healing.
AB  - Delayed union represents an ongoing failure of initial fracture management. It
      still occurs partly because the precise reason why a patient's fracture does not
      heal frequently is unknown. This article aims to outline the limited material
      available on the pathophysiology of delayed healing. The systemic status of the
      patient, local limb status before injury, the nature of the traumatic injury,
      local host response to the injury, potential negative impact of orthopaedic
      fracture care, and pharmacologic variables are considered.

PMID- 9917625
TI  - Mechanobiology of skeletal regeneration.
AB  - Skeletal regeneration is accomplished by a cascade of biologic processes that may
      include differentiation of pluripotential tissue, endochondral ossification, and
      bone remodeling. It has been shown that all these processes are influenced
      strongly by the local tissue mechanical loading history. This article reviews
      some of the mechanobiologic principles that are thought to guide the
      differentiation of mesenchymal tissue into bone, cartilage, or fibrous tissue
      during the initial phase of regeneration. Cyclic motion and the associated shear
      stresses cause cell proliferation and the production of a large callus in the
      early phases of fracture healing. For intermittently imposed loading in the
      regenerating tissue: (1) direct intramembranous bone formation is permitted in
      areas of low stress and strain; (2) low to moderate magnitudes of tensile strain
      and hydrostatic tensile stress may stimulate intramembranous ossification; (3)
      poor vascularity can promote chondrogenesis in an otherwise osteogenic
      environment; (4) hydrostatic compressive stress is a stimulus for chondrogenesis;
      (5) high tensile strain is a stimulus for the net production of fibrous tissue;
      and (6) tensile strain with a superimposed hydrostatic compressive stress will
      stimulate the development of fibrocartilage. Finite element models are used to
      show that the patterns of tissue differentiation observed in fracture healing and
      distraction osteogenesis can be predicted from these fundamental mechanobiologic
      concepts. In areas of cartilage formation, subsequent endochondral ossification
      normally will proceed, but it can be inhibited by intermittent hydrostatic
      compressive stress and accelerated by octahedral shear stress (or strain). Later,
      bone remodeling at these sites can be expected to follow the same mechanobiologic
      adaptation rules as normal bone.

PMID- 9917626
TI  - Experimental models of fracture repair.
AB  - Many mammalian and avian species have been used as models to study fracture
      healing. The individual animals, based on their size and other characteristics,
      are used to show the effects of different interventions on healing bone. The
      models may have fractures created by closed or open means or osteotomies.
      Fracture healing can be evaluated through histologic, mechanical, chemical, or
      biological studies. Internal fixation, external skeletal fixation, or no fixation
      may be used in the experiments. Results of fracture healing studies among animal
      species may conflict even when the same model is used in each species. These
      differences may be explained by anatomic, biochemical, and gene expression
      differences. Evaluation of the animal model is an important consideration when
      applying the results of any particular study to humans. Consensus regarding
      fracture healing develops from agreement between results of animal models and
      human clinical studies.

PMID- 9917628
TI  - The role of osteochondral progenitor cells in fracture repair.
AB  - The repair of a fracture necessarily entails synthesis of osseous tissue
      requiring the transformation of undifferentiated osteochondral progenitor cells
      to mature osteoblasts and chondrocytes. Owen and Friedenstein proposed that there
      are stem cells for all mesenchymal tissues, resident in bone marrow throughout
      life, that have a lineage comparable to that described for hematopoiesis.
      Subsequent with this initial study, marrow derived and periosteal derived
      progenitor cells have been shown to produce bone and cartilage in numerous in
      vivo and in vitro studies. The differentiation process appears to depend heavily
      on the influences of numerous cytokines, especially the transforming growth
      factor beta superfamily. Initial cartilage formation from progenitor cells is
      important in any secondary fracture repair. In the in vitro study of
      chondrogenesis, the marrow derived progenitor cells were shown to differentiate
      into their terminal phenotype, the hypertrophic chondrocyte, as indicated by the
      detection of Type X collagen messenger ribonucleic acid and protein. A
      concomitant elevation in the alkaline phosphatase level suggests that these cells
      are ready to mineralize. Despite the importance of these cells in fracture
      repair, the characterization of these cells and the mechanism of their
      differentiation have only begun to be explored.

PMID- 9917627
TI  - Initiation of fracture repair by bone morphogenetic proteins.
AB  - The potential for regeneration and repair of bone is well known. This article
      conveys the current progress in the realm of bone morphogenetic proteins and
      their potential for initiating fracture repair cascade. Demineralized bone matrix
      induces bone formation and has served as a model for the bone repair cascade. A
      family of bone morphogenetic proteins has been identified, isolated, and cloned
      from the demineralized bone matrix. Bone morphogenetic proteins are pleiotropic
      regulators of chemotaxis, mitosis, and differentiation. The bone morphogenetic
      protein receptors, Types I and II, bind bone morphogenetic proteins and act in
      collaboration to transduce the phosphorylation of Smad 1 and Smad 5, which enter
      the nucleus in partnership with Smad 4 to initiate bone morphogenetic protein
      responses including fracture healing. The accumulated information on bone
      morphogenetic proteins may aid in accelerating fracture repair and the potential
      use of bone morphogenetic protein antibodies to inhibit heterotopic bone
      formation and fibrodysplasia ossificans progressiva.

PMID- 9917629
TI  - Angiogenesis in fracture repair.
AB  - Fracture of bone disrupts its circulation and leads to necrosis and hypoxia of
      adjacent bone. Under normal circumstances, fractured bone undergoes the orderly
      regeneration of its component tissues with complete restoration of mechanical
      properties. Reestablishment of the circulation is an early event in fracture
      healing. Several experimental models of protracted, impaired, or compromised
      healing have been developed to evaluate the effects of angiogenic factors in
      accelerating or enhancing repair.

PMID- 9917630
TI  - Effects of electromagnetic fields in experimental fracture repair.
AB  - The clinical benefits of electromagnetic fields have been claimed for 20
      centuries, yet it still is not clear how they work or in what circumstances they
      should be used. There is a large body of evidence that steady direct current and
      time varying electric fields are generated in living bone by metabolic activity
      and mechanical deformation, respectively. Externally supplied direct currents
      have been used to treat nonunions, appearing to trigger mitosis and recruitment
      of osteogenic cells, possibly via electrochemical reactions at the electrode
      tissue interface. Time varying electromagnetic fields also have been used to heal
      nonunions and to stabilize hip implants, fuse spines, and treat osteonecrosis and
      osteoarthritis. Recent research into the mechanism(s) of action of these time
      varying fields has concentrated on small, extremely low frequency sinusoidal
      electric fields. The osteogenic capacity of these fields does not appear to
      involve changes in the transmembrane electric potential, but instead requires
      coupling to the cell interior via transmembrane receptors or by mechanical
      coupling to the membrane itself.

PMID- 9917631
TI  - Strain rate and timing of stimulation in mechanical modulation of fracture
      healing.
AB  - Fracture of the long bones results in a repair process that has the potential to
      restore the anatomic morphology and mechanical integrity of the bone without scar
      tissue. The repair process can occur in two patterns. In the first, under
      conditions of rigid stabilization, direct osteonal remodeling of the fracture
      line can occur with little or no external callus, a process known as direct bone
      repair. The second pattern of repair involves bridging of the fragments with
      external callus and formation of bone in the fracture site by endochondral
      healing. This type of repair is known as indirect bone healing and occurs under
      less rigid interfragmentary stabilization. The rate of healing and the extent of
      callus in this type of repair can be modulated by the mechanical conditions at
      the fracture site. Applying cyclic interfragmentary micromotion for short periods
      has been shown to influence the repair process significantly, and characteristics
      of this stimulus influence the healing response observed. In the current study, a
      short term interfragmentary cyclic micromovement applied at a high strain rate
      induced a greater amount of periosteal callus than the same stimulus applied at a
      low strain rate. This high strain rate stimulus applied later in the healing
      period significantly inhibited the progress of healing. The beneficial effect of
      this particular biophysic stimulus early in the healing period may be related to
      the viscoelastic nature of the differentiating connective tissues in the early
      endochondral callus. In the early endochondral callus, high rates of movement
      induce a greater deformation of the fracture fragments because of the stiffening
      of the callus. Alternatively, the transduction pathway may involve streaming
      potentials as a result of the high movement rate.

PMID- 9917632
TI  - Expression of bone morphogenetic proteins in fracture healing.
AB  - Fracture healing involves a complex interaction of many local and systemic
      regulatory factors. Recently, the presence of several bone morphogenetic proteins
      and their receptors in the fracture healing process has been described. During
      the early stages of fracture healing, only a minimum number of primitive cells
      are expressing bone morphogenetic proteins in the fracture callus. As the process
      of endochondral ossification proceeds, the presence of bone morphogenetic
      proteins and their receptors increases dramatically, especially in the primitive
      mesenchymal and chondrocytic cells. While the cartilaginous component of the
      callus matures with a concomitant decrease in the number of primitive cells,
      there is a concomitant decrease in presence of bone morphogenetic protein
      expressing cells. As osteoblasts start to lay down woven bone on the chondroid
      matrix, these osteoblastic cells express bone morphogenetic proteins and their
      receptors. The presence of bone morphogenetic proteins decreases, however, as
      lamellar bone replaces the primitive woven bone. A similar observation is seen in
      the areas of the callus undergoing intramembranous ossification. Initially,
      within several days after the fracture, periosteal cells and osteoblasts show
      intense expression of bone morphogenetic proteins and their receptors. As the
      woven bone is replaced with mature lamellar bone, the expression of bone
      morphogenetic protein decreases. These data and the knowledge of bone
      morphogenetic proteins' strong osteoinductive capacities suggest that individual
      bone morphogenetic proteins play important yet different roles during fracture
      repair.

PMID- 9917633
TI  - Transforming growth factor beta in fracture repair.
AB  - Transforming growth factor betas are a group of polypeptide growth factors that
      have a wide range of activities in the musculoskeletal and immunological systems.
      They are thought to play an important role in the development, induction, and
      repair of bone. This family of closely related genes includes the five known
      transforming growth factor betas and also the bone morphogenetic proteins. With
      the development of new techniques to analyze gene expression, the broad range of
      cellular activities regulated by transforming growth factor beta is beginning to
      be understood. The critical role that transforming growth factor beta plays in
      the regulation and stimulation of mesenchymal precursor cells for chondrocytes,
      osteoblasts, and osteoclasts is now emerging based on a series of in vitro
      studies. Although transforming growth factor betas appear to stimulate
      proliferation of precursor cells, it appears that transforming growth factor
      betas have an inhibitory effect on mature cell lines. In vivo studies indicate
      the presence of transforming growth factor beta protein and transforming growth
      factor beta gene expression in normal fracture healing, whereas exogenous
      transforming growth factor beta administration stimulates the recruitment and
      proliferation of osteoblasts in fracture healing. Although the cascade of events
      that leads to bone formation and repair is not completely understood,
      transforming growth factor beta's central role in the regulation of fracture
      healing is not disputed.

PMID- 9917634
TI  - Effects of mechanical factors on the fracture healing process.
AB  - An interdisciplinary study based on animal experiments, cell culture studies, and
      finite element models is presented. In a sheep model, the influence of the
      osteotomy gap size and interfragmentary motion on the healing success was
      investigated. Increasing gap sizes delayed the healing process. Increasing
      movement stimulated callus formation but not tissue quality. Typical
      distributions of intramembranous bone, endochondral ossification, and connective
      tissue in the fracture gap are quantified. The comparison of the mechanical data
      determined by a finite element model with the histologic images allowed the
      attribution of certain mechanical conditions to the type of tissue
      differentiation. Intramembranous bone formation was found for strains smaller
      than approximately 5% and small hydrostatic pressure (< 0.15 MPa). Strains less
      than 15% and hydrostatic pressure more than 0.15 MPa stimulated endochondral
      ossification. Larger strains led to connective tissue. Cell culture studies on
      the influence of strain on osteoblasts supported these findings. Proliferation
      and transforming growth factor beta production was increased for strains up to 5%
      but decreased for larger strains. Osteoblasts under larger strains (> 4%) turned
      away from the principal strain axis and avoided larger deformations. It is
      hypothesized that gap size and the amount of strain and hydrostatic pressure
      along the calcified surface in the fracture gap are the fundamental mechanical
      factors involved in bone healing.

PMID- 9917635
TI  - Potential role for gene therapy in the enhancement of fracture healing.
AB  - Various proteins have the potential to initiate and accelerate fracture healing.
      Although osteogenic growth factors are the most prominent of these, there also
      may be important roles for other agents including growth factor receptors,
      angiogenic factors, and cytokine antagonists. Gene based delivery systems offer
      the potential to achieve therapeutic levels of these proteins locally within the
      fracture site for sustained times. Moreover, these delivery systems may deliver
      their products in a more biologically active form than that achieved by the
      exogenous application of recombinant proteins. Genes may be transferred to
      fractures by direct in vivo delivery or by indirect ex vivo delivery, using viral
      or nonviral vectors. Two examples are described in this article. With an ex vivo
      procedure, it was possible to transfer lac Z and neo(r) marker genes to the bones
      of mice, using retroviral transduction of bone marrow stromal cells. Gene
      expression in vivo persisted for several weeks. This procedure has the advantage
      of providing not only gene products but also osteoprogenitor cells to sites of
      bone healing. In vivo, local transfer of the lucerifase and lac Z marker genes
      was accomplished in a segmental defect model in the rabbit using adenoviral
      vectors. Under these conditions, gene expression in most tissues in and around
      the defect lasted between 2 and 6 weeks. These data encourage additional
      development of gene therapy for fracture healing. Such developments should go
      hand in hand with studies in the basic biology of fracture healing.

PMID- 9917636
TI  - Potential role for direct gene transfer in the enhancement of fracture healing.
AB  - This paper describes the use of localized transient gene therapy for the
      augmentation of fracture healing. It introduces a method involving the delivery
      of plasmid deoxyribonucleic acid via a three dimensional matrix into a wound,
      with in vivo transfection of wound repair cells resulting, their subsequent
      expression of factors that condition the wound site and the promotion of healing.
      Based on experience with critical and noncritical defect models in small and
      large animals, the potential advantages of this approach are discussed and
      experimental evidence of promoting bone formation is provided. The studies show
      the potential of this technology not only to promote bone healing but also to
      repair or to regenerate other connective tissues.

PMID- 9917637
TI  - Enhancement of fracture healing by mechanical and surgical intervention.
AB  - Mechanical modulation of bone fracture repair and restoration to its structural
      strength must rely on the fundamental physical concept of remodeling according to
      the type of stress applied to immature or undifferentiated tissue. This article
      proposes the possible mechanisms of interaction between physical factors and
      cellular responses in healing long bone fractures and speculates on the
      advantages and limitations of different experimental models in evaluating these
      interactions. A revised classification system of fracture union types based on
      histomorphologic characteristics is introduced here as a reference standard in
      the studies of possible accelerating factors. Bone fracture union can follow more
      than one or two pathways, with various combinations of bone formation mechanisms,
      whereas there may be only one bone remodeling principle. There are definite
      mechanical and operative interventions that can provide effective enhancement to
      fracture healing. However, different intervention may limit its association to a
      specific healing mechanism. The key element in establishing these interactions is
      defining the precise cellular and molecular mechanisms in a quantitative manner.
      This can be achieved best by interdisciplinary research collaborations working on
      a higher level of expertise in each related field using standardized experimental
      models. Not only a basic understanding of the associated cellular reactions is
      necessary, but also the specific forms of mechanical stimulation, the dose
      effect, and its application timing must be determined and validated. Without this
      basic research effort, it would be difficult to transform such an augmentational
      modality into effective and reliable therapeutic regimens for clinical
      application. Furthermore, successful fracture repair enhancement must have proper
      new bone formation maintenance and remodeling through physiologic loading, or the
      initial stimulation process may be short lived and unable to reestablish the
      required biomechanical strength of the long bone. Finally, there is no substitute
      for a well organized and carefully controlled prospective clinical trial in
      establishing the validity of any bone fracture healing enhancement modality,
      regardless of its nature and form of application.

PMID- 9917638
TI  - Mechanical influences on tibial fracture healing.
AB  - Selected studies are summarized that measure interfragmentary fracture
      displacements in 6 degrees of freedom at intervals throughout healing in groups
      of patients with tibial diaphyseal fractures treated by external skeletal
      fixation. The results are compared with those obtained from experimental studies
      in which the ideal mechanical conditions for fracture healing were predicted. A
      finite element analysis model of the healing tibial fracture also was developed.
      Measured data were used for the analysis, and stress and strain patterns were
      defined for different stages of healing. Interfragmentary movement measured in
      the first 6 weeks after injury usually is a magnitude smaller in patients treated
      by external fixation than in patients treated with cast immobilization. This
      movement can be much smaller than that predicted to be optimal by experimental
      studies. A greater amplitude can be achieved, even in stable fractures, by
      ensuring patient activity. The interfragmentary movement is elastic during
      loading activity and is generally sinusoidal during steady walking. At the time
      of dynamization (the unlocking of the frame), a permanent set occurs at the
      fracture site in all planes. The cyclical movement range in each plane often
      decreases immediately after unlocking. The model analysis study of fracture
      healing predicts that tissue damage may occur in the later (hard callus) phase of
      healing, even while the fixation device is in place, because of abnormally high
      stresses and strains. This study indicates that fracture mechanics should be
      controlled more rigorously to provide amplitudes of movement in the first 4 to 6
      weeks after fracture. The rigidity of fixation should be increased in the
      subsequent weeks until the fracture has healed and the frame is removed.

PMID- 9917639
TI  - Bone regeneration and fracture healing. Experience with distraction osteogenesis
      model.
AB  - The relation between physical forces and the processes of bone regeneration and
      healing remains incompletely understood. Gaps in understanding of these processes
      stem in part from models that produce inadequate amounts of new bone for study.
      Bone created through the use of distraction osteogenesis provides an attractive
      substrate for the study of mechanical forces and their effects on bone formation
      because this technique produces large volumes of new bone in a controlled
      fashion. The optimal mechanical environment in which bone formation occurs
      clinically has not been fully determined. In laboratory studies, however, the
      mechanical environment can be manipulated, and resultant changes in bone
      formation can be measured. To investigate how changes in strain environment
      influence patterns of bone formation, a bilateral New Zealand White rabbit model
      of bilateral distraction osteogensis was implemented. When a stiffener was
      applied to the external distractor, computation analyses predicted a sevenfold to
      eightfold decrease in all strain measures. These reductions in gap strains
      appeared to induce significant decreases in bone volume fraction and mean
      trabecular thickness. When osteotomies were created at a 30 degrees angle to the
      bony axis to generate more shear within the gap tissue, changes in the
      distribution of gap strains and resultant new bone architecture were observed.
      Specific correlations between changes in tissue level strains and the pattern of
      bone regeneration were seen in both experiments. These results provide direct in
      vivo evidence that pluripotential gap tissues are sensitive to their physical
      surroundings. Mechanisms responsible for this sensitivity might include
      vascularity, stem cell supply, and scaffolding architecture. The process of bone
      formation in distraction osteogenesis appears to be related to bone formation
      processes associated with more common conditions. The distraction osteogenesis
      model described suggests a mechanism for bone formation that seems applicable to
      other more common processes associated with bone formation, including fracture
      healing and impaired fracture healing.

PMID- 9917640
TI  - Clinical effects of electromagnetic and electric fields on fracture healing.
AB  - The clinical use of electric and electromagnetic fields for fracture healing
      applications began in the early 1970s. Since then, several technologies have been
      developed and shown to promote healing in difficult to heal fractures. The
      development of these devices has been aided in recent years by basic research and
      several well controlled clinical trials. This review provides a brief description
      of the different techniques and their respective clinical utility. Finally,
      future directions in basic and clinical research are outlined to exploit fully
      the usefulness of these noninvasive bone growth stimulation technologies.

PMID- 9917641
TI  - Enhancement of fracture healing by low intensity ultrasound.
AB  - Fracture healing is a highly complex regenerative process that is essentially a
      replay of developmental events. These events include the action of many different
      cell types, a myriad of proteins, and active gene expression that in the majority
      of cases ultimately will restore the bone's natural integrity. Several biologic
      and biophysical approaches have been introduced to minimize delayed healing and
      nonunions, some with promising results. One example of such an approach is low
      intensity pulsed ultrasound, a noninvasive form of mechanical energy transmitted
      transcutaneously as high frequency acoustical pressure waves in biologic
      organisms. Numerous in vivo animal studies and perspective double blind placebo
      controlled clinical trials have shown that low intensity ultrasound is capable of
      accelerating and augmenting the healing of fresh fractures. Preliminary evidence
      suggests efficacy in the treatment of delayed healing and nonunions as well. This
      article reviews the animal and clinical studies that consider the effects of
      ultrasound on fracture healing, and the in vivo and in vitro work that strives to
      identify the biologic mechanism(s) responsible for the ultrasound induced
      enhancement of osteogenesis and fracture healing.

PMID- 9917642
TI  - The effect of reamed and nonreamed intramedullary nailing on fracture healing.
AB  - Intramedullary nailing has revolutionized the treatment of fractures. It is
      important to be aware of the biological and mechanical effects of reaming and
      nailing on bone. Most nails are substantially stiffer than bone, but because of
      their location in the medullary canal do not have nearly as adverse an effect on
      callus strength as plates. Reaming and nailing embolizes marrow contents into the
      systemic circulation and reduces blood flow to the total bone and cortex by 30%
      to 80%. This results in a hyperemic reaction that revascularizes the cortex
      depending on the type of nail used. Preservation of the soft tissue envelope
      around the fracture enhances this response resulting in fracture healing ratio of
      98% when closed nailing techniques are used. The primary advantage of nonreamed
      nailing is better preservation of the blood supply to the cortex whereas the
      major advantage of reamed nailing is a more rigid construction, stronger
      implants, and earlier fracture union.

PMID- 9917643
TI  - Enhancement of fracture healing with autogenous and allogeneic bone grafts.
AB  - The factors contributing to a delayed union or nonunion are many. In general they
      may be divided into three major categories: deficiencies in vascularity and
      angiogenesis, deficiencies in the robustness of the chondroosseous response, and
      deficiencies in stability, strain, or physical continuity. Frequently,
      deficiencies in more than one category are present, thus complicating the
      approach to therapy. For a bone grafts to enhance fracture healing, it must
      provide or stimulate that which is deficient. Autogenous fresh cancellous and
      cortical bone most frequently are used, but other common grafts include
      allogeneic frozen, freeze dried, or processed allogeneic cortical,
      corticocancellous and cancellous grafts, and demineralized bone matrix. These
      grafts have varying capacities to provide active bone formation, to induce bone
      formation by cells of the surrounding soft tissue, and to serve as a substrate
      for bone formation. However, the graft cannot exert its biologic activity in
      isolation, dependent as it is on the surrounding environment for cells to respond
      to its signals and, in some cases, for blood supply. The mechanical environment
      of the graft site is also important. Successful graft incorporation requires that
      an appropriate match must be made between the biologic activity of a bone graft,
      the condition of the perigraft environment, and the mechanical environment. The
      task of the clinician who performs a bone grafting procedure for the enhancement
      of fracture healing is to choose the right graft or combination of grafts for the
      biologic and mechanical environment into which the graft will be placed.

PMID- 9917644
TI  - Mesenchymal stem cells in osteobiology and applied bone regeneration.
AB  - Bone marrow contains a population of rare progenitor cells capable of
      differentiating into bone, cartilage, muscle, tendon, and other connective
      tissues. These cells, referred to as MSCs, can be purified and culture expanded
      from animals and humans. This review summarizes recent experimentation focused on
      characterizing the cellular aspects of osteogenic differentiation, and
      exploration of the potential for using autologous stem cell therapy to augment
      bone repair and regeneration. The authors have completed an array of preclinical
      studies showing the feasibility and efficacy of MSC based implants to heal large
      osseous defects. After confirming that syngeneic rat MSCs could heal a critical
      size segmental defect in the femur, it was established that human MSCs form bone
      of considerable mechanical integrity when implanted in an osseous defect in an
      immunocompromised animal. Furthermore, bone repair studies in dogs verify that
      the technology is transferable to large animals, and that the application of this
      technology to patients at geographically remote sites is feasible. These studies
      suggest that by combining MSCs with an appropriate delivery vehicle, it may be
      possible to offer patients new therapeutic options.

PMID- 9917645
TI  - Clinical use of marrow osteoprogenitor cells to stimulate osteogenesis.
AB  - This review of 15 years research into various methods and techniques of using
      marrow osteoprogenitor cells shows that marrow grafts can be useful for numerous
      skeletal healing problems, but not all. The method offers considerable
      improvement over standard open iliac crest grafting and provides an attractive
      and advantageous method of stimulating osteogenesis in the management and
      prevention of nonunion.

PMID- 9917646
TI  - Current understanding of osteoconduction in bone regeneration.
AB  - Bone tissue is osteoconductive. In particular, cancellous bone with its porous
      and highly interconnected trabecular architecture allows easy ingrowth of
      surrounding tissues. When placed in an osseous environment, living tissue for the
      host bed migrates into the cancellous structure, which results in new bone
      formation and incorporation of that structure. This is the process of
      osteoconduction. The mineral and collagenous components of bone are
      osteoconductive. Osteoconduction also is observed in fabricated materials that
      have porosity similar to that of bone structure. Corallin ceramics,
      hydroxyapatite beads, and combinations of hydroxyapatite and collagen all have
      osteoconductive properties, and porous metals and biodegradable polymers.
      Osteoconduction appears to be optimized in devices that mimic not only bone
      structure, but also bone chemistry. The incorporation of calcium salts and
      collagen by osteoconductive matrices leads to more complete ingrowth with new
      bone formation.

PMID- 9917647
TI  - Potential role of bone morphogenetic proteins in fracture healing.
AB  - Since their discovery, bone morphogenetic proteins have held the promise for use
      in various orthopaedic diseases. One of the largest areas of likely application
      is the area of fracture repair. Although millions of fractures occur annually and
      the majority heal satisfactorily, 5% to 10% go on to delayed union or nonunion.
      Bone morphogenetic proteins may be able to improve bony healing in these
      conditions and perhaps enhance the healing of fractures that otherwise heal
      satisfactorily. This study examines the preclinical data to support the concept
      of enhancing bony healing and discusses the preliminary data from clinical trials
      using bone morphogenetic proteins to augment bony healing. Although the potential
      clinical uses of bone morphogenetic proteins in fracture healing remain
      significant, this potential has yet to be realized.

PMID- 9917648
TI  - Potential role of fibroblast growth factor in enhancement of fracture healing.
AB  - Fibroblast growth factors are present in significant amounts in bone and several
      studies have suggested that they may be involved in normal fracture healing. It
      is well established that fibroblast growth factors have mitogenic and angiogenic
      activity on mesoderm and neuroectoderm derived cells. Of particular interest as a
      member of the fibroblast growth factor family, basic fibroblast growth factor
      stimulates mitogenesis, chemotaxis, differentiation, and angiogenesis. It also
      plays an important role in the development of vascular, nervous, and skeletal
      systems, promotes the maintenance and survival of certain tissues, and stimulates
      wound healing and tissue repair. Animal studies have shown that the direct
      injection of fibroblast growth factor into fresh fractures stimulates callus
      formation, which provides mechanical stability to the fracture, accelerates
      healing, and restores competence. The matrix used to present the fibroblast
      growth factor at the fracture site plays a critical role in the effectiveness of
      the treatment. The evaluation of injectable basic fibroblast growth factor in a
      sodium hyaluronate gel for its effectiveness in stimulating fracture healing is
      described. When applied directly into a freshly created fracture in the rabbit
      fibula, a single injection of the basic fibroblast growth factor and hyaluronan
      results in the stimulation of callus formation, increased bone formation, and
      earlier restoration of mechanical strength at the fracture site. The hyaluronan
      gel serves as a reservoir that sequesters the basic fibroblast growth factor at
      the injection site for the length of time necessary to create an environment
      conducive to fracture healing. It is concluded that basic fibroblast growth
      factor and sodium hyaluronate act synergistically to accelerate fracture healing
      and that the combination is suitable for clinical evaluation as a therapy in
      fracture treatment.

PMID- 9917649
TI  - The potential role of transforming growth factor beta in fracture healing.
AB  - As shown in previous studies, the transforming growth factor beta superfamily of
      growth factors is involved in many aspects of skeletal development and
      regulation, including fracture repair and bone regeneration. Several studies have
      shown transforming growth factor beta messenger ribonucleicacid and protein
      expression in cells comprising fracture callus. In healing fractures in a chick
      model, differential isoform expression of the transforming growth factor betas
      was observed by in situ hybridization, with more prominent expression of the
      transforming growth factor beta 2 and transforming growth factor beta 3 isoforms.
      Small amounts of transforming growth factor beta 1 were present in early callus
      and increased in expression later during chondrogenesis and endochondral
      ossification. These findings resemble those reported in rat and human fracture
      callus. Transforming growth factor beta 4 expression was not significant in the
      chick fracture model. Transforming growth factor beta can function as a morphogen
      when injected subperiosteally, inducing cartilage and bone formation that
      morphologically resembles many of the events occurring in fracture callus.
      Exogenous transforming growth factor beta has been used in several critical size
      defect models of bone regeneration and fracture healing, with most of the studies
      showing increased bone or callus formation and increased mechanical stability.
      Numerous variables, including markedly different dose ranges and differing
      isoforms, dosing regimens, delivery methods, animal models, and various times and
      endpoint measures for analysis, make it difficult to comparatively assess the
      effects of transforming growth factor beta on bone healing. Additional study is
      necessary to satisfactorily determine the role of transforming growth factor beta
      in normal fracture healing and its potential for use in augmenting this process.

PMID- 9917650
TI  - Potential role of insulinlike growth factors in fracture healing.
AB  - Several lines of evidence suggest that the insulinlike growth factors play a role
      in fracture healing. They promote cell proliferation and matrix synthesis by
      chondrocytes and osteoblasts, the two cell types largely responsible for the
      formation of fracture callus. Circulating levels of insulinlike growth factor I
      and bone mineral density decrease with increasing age, and administration of
      insulinlike growth factor I increases bone turnover in patients with low bone
      mineral density. Insulinlike growth factor I may accelerate the normal healing of
      intramembranous bone defects, inducing the healing of defects that otherwise
      would not heal. An important role of insulinlike growth factor I is to mediate
      many of the actions of growth hormone on the skeleton. Considerable effort has
      been devoted to testing the effect of growth hormone and, thereby, indirectly
      that of insulinlike growth factor I on fracture healing. These studies have
      yielded such disparate results that no general conclusions regarding the effect
      of growth hormone (or of growth hormone dependent insulinlike growth factor I) on
      fracture healing currently can be drawn. Additional studies are needed to clarify
      the role of the insulinlike growth factors in the fracture healing process and to
      determine how their anabolic actions can be enlisted in the clinical enhancement
      of fracture healing.

PMID- 9917651
TI  - Osteonecrosis of the femoral head. Potential treatment with growth and
      differentiation factors.
AB  - Basic and clinical research have shown the efficacy of various cellular mediators
      (bone morphogenetic proteins, interleukins, angiogenic growth factors) in healing
      bone defects. The potential application of these growth and differentiation
      factors to other musculoskeletal conditions, including osteonecrosis of the
      femoral head, only recently has been explored. Osteonecrosis is a disease of
      unknown pathogenesis that usually progresses to hip joint destruction
      necessitating total hip arthroplasty. The pathology involves ischemic events
      followed by death of bone and marrow elements. A process of repair then is
      initiated, but unless the lesion is small (less than 15% of the femoral head
      involved), this repair process is usually ineffective. The net result is
      weakening of subchondral bone with subsequent collapse of the articular surface.
      Because the results of hip arthroplasty in patients with osteonecrosis are
      relatively poor, much focus has been on modalities aimed at femoral head
      preservation. The surgical alternatives may include core decompression,
      osteotomy, nonvascularized, and vascularized bone grafting, which might be
      enhanced with the use of growth and differentiation factors. At least three of
      these factors are potential candidates as therapeutic modalities: cytokines (such
      as interleukins, tumor necrosis factors, and signaling molecules such as
      fibroblast growth factors, platelet derived growth factors, insulinlike growth
      factors, and transforming growth factor betas), bone morphogenetic proteins, and
      angiogenic factors. Despite considerable effort, evaluation of these growth and
      differentiation factors has been hampered by the lack of an animal model that
      adequately simulates the pathology of osteonecrosis in humans. Therefore,
      investigators have attempted to model certain aspects of the disease process.
      Recently, several investigators have attempted to mimic osteonecrosis in the
      femoral head of large mammals by combinations of devascularization, freezing,
      osteotomy of the femoral neck, or creation of a head defect. Results from some of
      these studies have confirmed the potential for growth and differentiation factors
      to effect more rapid healing and filling of defects with biomechanically
      competent and viable bone. The application of this therapy shows promise, and
      clinical studies on efficacy and safety are ongoing.

PMID- 9917652
TI  - Bone repair and enhancement clinical trial design. Spine applications.
AB  - Spine fusion represents over half of all current bone grafting procedures. It is
      an important clinical area for bone augmentation because use even of the most
      successful graft material, autogenous iliac crest bone, is fraught with an
      unacceptably high failure rate. Various new options that biologically will
      control bone induction currently are under development. To prevent unnecessary
      clinical failures, it is important that surgeons understand the principles of
      clinical trial design, whether they actively are using the reported results or
      simply reviewing them in an effort to decide if they will use the new technology
      in their own practice. This review highlights the important issues relevant to
      designing a clinical trial for studying the efficacy of a bone augmentation
      product in a spine application. Some of the design challenges are generic, but
      others are unique to the spine because of difficulty in defining a clear
      diagnostic group, difficulty in noninvasively assessing the technical success of
      surgery, and frequent dissociation of the clinical and radiographic results.

PMID- 9917653
TI  - Proper design of clinical trials for the assessment of bone graft substitutes.
AB  - To assess the effectiveness and safety of engineered bone graft substitutes
      proper, clinical trials will need to be performed. Although the randomized
      placebo controlled prospective clinical trial is the gold standard, clinical
      trials of this design are difficult to perform in the surgical setting. At this
      writing, several clinical trials evaluating bone graft materials have been
      performed, and much was learned toward improving the design of future studies.
      This article reviews alternatives to the placebo controlled randomized clinical
      trials in the surgical setting. The importance of long term surveillance is
      emphasized.

PMID- 9917654
TI  - Breakout session. 1: Definitions of fracture repair.

PMID- 9917655
TI  - Breakout session. 2: Fracture repair process.

PMID- 9917656
TI  - Breakout session. 3: Mechanical enhancement of callus healing.

PMID- 9917657
TI  - Breakout session. 4: Biophysical enhancement.

PMID- 9917658
TI  - Breakout session. 5: Biologic enhancement of fracture repair.

PMID- 9917659
TI  - Breakout session. 6: Regional gene therapy.

PMID- 9917660
TI  - The knee-joint anchylosed at a right angle--restored nearly to a straight
      position after the excision of a wedge-shaped portion of bone, consisting of the
      patella, condyles and articular surface of the tibia. 1845.

PMID- 9917661
TI  - The Coventry Award. Modular tibial insert micromotion. A concern with
      contemporary knee implants.
AB  - This study investigates micromotion between modular tibial components, one of the
      causes of wear on the undersurface of polyethylene inserts. The authors measured
      motion at the interface of nine contemporary total knee implant designs by
      mechanically testing the implants in a servohydraulic testing machine.
      Anteroposterior and mediolateral motion between the tibial insert and baseplate
      were measured with an extensometer placed across the interface. These tests
      revealed that in all implants analyzed, sufficient motion occurred to create
      fretting at the modular interface. Although the testing configuration in this
      study was not a stimulation of in situ loading patterns, the authors observed
      hundreds of microns of motion even under a 100 N load and variability between
      implants of the same design, showing that there is room for improvement among
      locking mechanisms in modular total knee implants.

PMID- 9917662
TI  - The Ranawat Award. Comparison of surgical approaches in total knee arthroplasty.
AB  - A series of 123 revision total knee replacements performed at three centers and
      followed up for 2 to 4 years was evaluated. In cases in which exposure could be
      obtained with undue tension on the patellar tendon, the surgical approach was
      modified using either quadriceps turndown (14 cases) or tibial tubercle osteotomy
      (15 cases). The remaining 94 patients underwent a standard operative approach
      that consisted of a medial parapatellar capsular incision which in 31 cases was
      combined with a quadriceps snip. The results were compared using the Knee Society
      clinical score, a patient satisfaction survey, and a patellofemoral
      questionnaire. Postoperatively, the group of patients who had a quadriceps snip
      was equivalent to the group of patients who underwent a standard approach in
      every parameter measured, and the groups therefore were combined for comparison
      purposes. The patients who had quadriceps turndown and the tibial tubercle
      osteotomy had equivalent scores postoperatively both of which were significantly
      lower than the standard group. The group of patients who had quadriceps turndown
      had a significantly greater increase in arc of motion than the tibial tubercle
      osteotomy group. The tibial tubercle osteotomy group had a lower degree of
      extension lag but a higher percentage of patients who had difficulty with
      kneeling and stooping and a higher percentage of patients who had difficulty with
      kneeling and stooping and a higher percentage of patients who thought the surgery
      was unsuccessful in relieving pain and unsuccessful in returning them to normal
      daily activities.

PMID- 9917663
TI  - Total knee arthroplasty in patients 55 years old or younger. 10- to 17-year
      results.
AB  - Seventy-four consecutive total knee arthroplasties in 54 patients who were 55
      years of age or younger (average age 43 years) were reviewed. All patients had a
      minimum followup of 10 years with an average followup of 13 years (range, 10-17
      years). No patients died or were lost to followup. The preoperative diagnosis was
      rheumatoid arthritis in 47, gonarthrosis in 12, posttraumatic arthritis in six,
      osteonecrosis in three, hemophilia in two, and one patient each with pigmented
      villonodular synovitis, tuberculosis, systemic lupus erythematosus, and
      achondroplasia. The knee score improved from an average of 36 points (range, 10
      80 points) preoperatively to 84 points (range, 37-100 points) at latest followup.
      The functional score improved from 45 points (range, 0-100 points) to 60 points
      (range, 0-100 points) at latest followup. Two patients had their implants
      revised: one at 3 years because of ligamentous laxity and one at 13 years because
      of aseptic loosening of the tibial component. There were no deep infections.
      There were no radiographically loose implants at latest followup. The implant
      survival to revision at 10 years was estimated at 99% (confidence limit, 96%
      100%). The implant survival to revision at 15 years was estimated at 95%
      confidence limit, 88%-100%). Cemented total knee arthroplasty in the young
      patient is a reliable procedure and has excellent results at 13-year followup
      with an estimated survivorship of 99% at 10 years.

PMID- 9917664
TI  - Total knee arthroplasty in patients who were obese with 10 years followup.
AB  - The 10-year results of primary total knee arthroplasty in patients who were obese
      were evaluated. In a 2-year period, 120 patients had 165 primary, posterior
      stabilized, cemented total knee replacements with metal backed tibial components.
      After exclusions, 56 patients (73 knees) were available for study. Twenty-two
      patients (32 knees) were classified as obese, and 34 patients (41 knees) were
      classified as nonobese. At 10 years followup, patients who were obese had lower
      Knee Society function scores than had the patients who were nonobese (mostly
      attributable to more difficulty with stair climbing). Patients who were obese had
      poorer patellar scores at 10 years. Bilaterality was more common in patients who
      were obese and preoperative knee scores were lower. Minor nonprogressive
      radiolucent lines were seen more commonly in the patients who were obese.
      Overall, however, 10-year Hospital for Special Surgery scores and Knee Society
      scores for patients who were obese were comparable with scores for patients who
      were nonobese and given lower preoperative Hospital for Special Surgery scores,
      improvement in knee score was greater. Revision rates in patients who were obese
      were not higher than in patients who were nonobese at 10 years followup. More
      study is needed of the subgroup of patients who were morbidly obese.

PMID- 9917665
TI  - Revision of failed cementless total knee implants with cement.
AB  - Between 1986 and 1996, 268 revision total knee replacements were performed.
      Revisions for aseptic loosening were reviewed prospectively. Sixty-three patients
      had implants revised for aseptic loosening. Thirty-six of the patients had
      revisions of cemented constructs, whereas 27 of the patients had revisions of
      cementless constructs. The average time before revision for the cemented group
      was 86 months. The average time to revision for the cementless group was only 43
      months. Fifty-two percent of the patients in the cementless group had revision of
      their implants within 2 years of their index arthroplasty. The average pain free
      interval for the cementless group was only 11 months with 63% of the patients
      having no pain relief after their index arthroplasty. The average postoperative
      score for the cementless group was 88, whereas the average postoperative score
      for the cemented group was 82. Revision of failed cementless total knee implants
      with cement is a reliable procedure. Results are similar to those of cemented
      knees revised with cement.

PMID- 9917666
TI  - Flexion instability after primary posterior cruciate retaining total knee
      arthroplasty.
AB  - Between 1990 and 1995, 25 painful primary posterior cruciate ligament retaining
      total knee arthroplasties were revised for flexion instability. These patients
      shared typical clinical presentations that included a sense of instability
      without frank giving way, recurrent knee joint effusion, soft tissue tenderness
      involving the pes anserine tendons and the retinacular tissue, posterior
      instability of 2+ or 3+ with a posterior drawer or a posterior sag sign at 90
      degrees flexion, and above average motion of their total knee arthroplasty. The
      primary total knee arthroplasty was performed for osteoarthritis in 23 patients
      and rheumatoid arthritis in two patients. There were 13 male and 12 female
      patients and their mean age was 65 years (range, 35-77 years). Before the
      revision operation, Knee Society knee scores averaged 45 points (range, 17-68
      points) and function scores averaged 42 points (range, 0-60 points). Twenty-two
      of the knee replacements were revised to posterior stabilized implants and three
      underwent tibial polyethylene liner exchange only. Nineteen of the 22 knee
      replacements revised to a posterior stabilized implant were improved markedly
      after the revision surgery. Only one of three knee replacements that underwent
      tibial polyethylene exchange was improved. After the revision for flexion
      instability, Knee Society knee scores averaged 90 points (range, 82-99 points)
      and function scores averaged 75 points (range, 45-100 points) for the 20 knees
      with a successful outcome. This study suggests that flexion instability can be a
      cause of persistent pain and functional impairment after posterior cruciate
      ligament retaining total knee arthroplasty. A revision operation that focuses on
      balancing the flexion and extension spaces, in conjunction with a posterior
      stabilized knee implant, seems to be a reliable treatment for symptomatic flexion
      instability after posterior cruciate retaining total knee arthroplasty.

PMID- 9917667
TI  - In vivo anteroposterior femorotibial translation of total knee arthroplasty: a
      multicenter analysis.
AB  - A study was conducted to determine in vivo femorotibial contact patterns for
      subjects having a posterior cruciate retaining or posterior cruciate substituting
      total knee arthroplasty. Femorotibial contact of 72 subjects implanted with a
      total knee replacement, performed by five surgeons, was analyzed using video
      fluoroscopy. Thirty-one subjects were implanted with a posterior cruciate
      retaining total knee replacement with a flat polyethylene posterior lipped
      insert, 12 with a posterior cruciate retaining total knee replacement with a
      curved insert, and 29 with a posterior cruciate substituting total knee
      replacement. Each subject performed successive deep knee bends to maximum
      flexion. Video images at 0 degree, 30 degrees, 60 degrees, and 90 degrees flexion
      were downloaded onto a workstation computer. Femorotibial contact paths were
      determined for the medial and lateral condyles using an interactive model fitting
      technique. Femorotibial contact anterior to the tibial midline in the sagittal
      plane was denoted as positive and contact posterior was denoted as negative.
      Analysis of average femorotibial contact pathways of both posterior cruciate
      retaining designs revealed posterior femorotibial contact in full extension with
      anterior translation of femorotibial contact commonly observed in midflexion and
      terminal flexion. In posterior cruciate substituting designs, anterior femoral
      translation was seen medially at 30 degrees to 60 degrees flexion but rarely was
      observed laterally. Posterior femoral rollback laterally from full extension to
      90 degrees flexion was seen in 100% of subjects implanted with a posterior
      cruciate substituting total knee replacement, versus 51.6% (posterior lipped
      polyethylene insert) and 58.3% (curved insert) of those with a posterior cruciate
      retaining total knee replacement. Data from this multicenter study are remarkably
      similar to previous fluoroscopy data from a single surgeon series, showing a lack
      of customary posterior femoral rollback in both posterior cruciate retaining
      designs, and conversely showing an average anterior femoral translation with knee
      flexion. Posterior femoral rollback, less than in normal knees, routinely was
      observed in posterior cruciate substituting total knee arthroplasty, attributed
      to engagement of the femoral component cam with the tibial post. The abnormal
      anterior femoral translation observed in posterior cruciate retaining total knee
      arthroplasty may be a factor in premature polyethylene wear observed in retrieval
      studies.

PMID- 9917668
TI  - Femoral component failure in hybrid total knee arthroplasty.
AB  - From 1986 to 1991, 74 consecutive hybrid total knee arthroplasties (in 65
      patients) of a single design were performed at the authors' institution. Seven
      patients (eight knees) died with well functioning replacements during the
      surveillance period. One patient refused to participate in any followup efforts
      because of billing disputes. This left 65 total knee arthroplasties (57 patients)
      for review. There were 35 men and 22 women with an average age of 60 years
      (range, 27-83 years) at the time of arthroplasty. The underlying diagnosis was
      osteoarthritis in 46 knees, rheumatoid arthritis in six knees, and other in four
      knees. The average length of followup was 7.4 years (range, 5-10 years), and no
      patients were lost to followup. The Knee Society scores improved from an average
      of 37 preoperatively to 84 at latest followup. The functional score improved from
      49 to 69 at latest followup. Ten (13.8%) knees required revision surgery. Eight
      of the nine knees that were revised had femoral component problems, including a
      loose component in six and a fractured component in two. One knee was revised for
      polyethylene wear with secondary osteolysis and one was revised elsewhere in
      which the operative details are unknown. The implant survival to revision at 5
      years was 89% and 85% at final followup. Femoral component fixation in hybrid
      total knee arthroplasty in unreliable with this component design. In light of the
      excellent 10- to 15-year results of cemented condylar knee designs it is thought
      that hybrid fixation should be abandoned.

PMID- 9917669
TI  - Cement versus cementless fixation in total knee arthroplasty.
AB  - A prospectively studied group of 55 uncemented Press Fit Condylar total knee
      arthroplasties was compared retrospectively with a matched group of 51 cemented
      Press Fit Condylar total knee arthroplasties at a mean of 10 years after
      operation. For the cemented group, the pain and function scores improved from 32
      and 45 preoperatively to 95 and 77, respectively. For the uncemented group the
      scores improved from 33 and 50 preoperatively to 93 and 60, respectively. There
      were 10 revisions in the uncemented group for femoral or tibial aseptic loosening
      or osteolysis compared with two revisions in the cemented group. Exclusive of
      problems related to patellar metal backing, survival to revision for aseptic
      failure or radiographic loosening was 72% in the uncemented group and 94% in the
      cemented group at 10 years. A significantly higher revision rate was found in the
      uncemented compared with cemented total knee arthroplasty of the Press Fit
      Condylar design.

PMID- 9917670
TI  - Is it necessary to cement the tibial stem in cemented total knee arthroplasty?
AB  - An in vitro study was performed using a singular unibody design CoCr tibial
      baseplate with fins to test the hypothesis that the addition of cement
      surrounding the tibial stem decreases micromotion of the tibial tray in cemented
      total knee arthroplasty. Five configurations were tested. Significant micromotion
      occurred with a cementless stem and a 1 mm cement mantle under the tibial tray.
      However, if the cement mantle beneath the tibial baseplate was increased to 3 mm,
      excellent stability of the implant was seen regardless of whether the tibial stem
      was left uncemented. In this particular component design, implant stability was
      enhanced with the addition of cement surrounding the tibial stem unless the
      cement mantle beneath the tibial tray was increased to 3 mm.

PMID- 9917671
TI  - Is the routine examination of surgical specimens worthwhile in primary total knee
      arthroplasty?
AB  - Two thousand two hundred eighty-nine consecutive primary total knee
      arthroplasties performed between 1993 and 1996 were reviewed retrospectively to
      assess the utility and cost effectiveness of the routine examination of surgical
      specimens. In those cases where a discrepancy was seen between the clinical and
      pathologic diagnoses, the records were reviewed carefully and those patients were
      contacted to determine whether their subsequent treatment was altered as a result
      of the pathologic findings. In 10 cases there was a potentially important
      discrepancy between the clinical and pathologic diagnoses. In none of those 10
      cases was the subsequent treatment of the patient altered as a result of the
      pathologic findings. This study suggests a reexamination of regulations that
      mandate the routine pathologic review of surgical specimens from primary total
      knee arthroplasties.

PMID- 9917672
TI  - Patient comorbidity: relationship to outcomes of total knee arthroplasty.
AB  - One hundred six patients treated consecutively with total knee arthroplasty were
      evaluated to determine whether preoperative comorbidity (as measured by patient
      class, knee score, short form, anesthesia severity assessment, and number of
      medical comorbidities) correlated with perioperative and postoperative outcomes,
      including length of stay, total (and specific) hospital charges, and validated
      outcome scores. The length of stay for total knee arthroplasty was longer in
      patients who had lower preoperative knee scores and for patients with greater
      medical and musculoskeletal morbidity. Greater total hospital costs were
      associated with Class C patients and patients with poor anesthesia morbidity
      ratings. Patients who were debilitated medically and had four or more risk
      factors had decreased postoperative outcome scores. Preoperative medical and
      musculoskeletal morbidity influence the results of total knee arthroplasty. These
      findings may be useful to surgeons for optimizing resource utilization and
      outcomes in patients undergoing total knee arthroplasty. These data must be
      accounted for when contrasting total knee arthroplasty results between different
      surgeons and institutions.

PMID- 9917673
TI  - Patient outcomes after knee replacement.
AB  - A prospective, observational cohort investigation was performed to help
      understand the impact of knee replacement on patients with knee osteoarthritis in
      community practice. Of those, 291 patients (330 knees) were eligible and willing
      to participate. Forty-eight orthopaedic surgeons referred 563 patients from 25
      institutions within the state of Indiana. Demographics, patient completed health
      status, satisfaction, independent radiographic measures, surgeon reported
      intraoperative factors, hospital discharge factors, and independent physical
      examinations were recorded. A minimum 2-year followup was obtained in 92% of the
      patients. At followup, 88% were satisfied, 3% were neutral, and 9% were
      dissatisfied with the results of their knee surgery. The physical composite score
      improved from 27.4 +/- 0.4 (range, 13.3-50.3) to 37.7 +/- 0.7 (range, 12.9-61.3)
      at two years. Maximal improvement in physical composite score was seen in
      patients who had their surgery performed in institutions that performed greater
      than 50 knee replacements per year in patients with Medicare insurance; who had a
      better mental health status at baseline; who had surgery performed on Monday,
      Friday, or Saturday; who were older; who were treated with a posterior cruciate
      sparing device; and who had worse preoperative function. A lower likelihood of
      complications were found with surgeons who performed greater than 20 knee
      replacements per year; midweek surgeries; in patients with more severe
      preoperative knee dysfunction; patients with fewer comorbidities; patients with
      less preoperative stiffness; patients being treated by younger surgeons; and in
      patients undergoing unilateral knee replacement. Among voluntarily participating
      physicians, knee replacement can be a highly effective medical technology with
      high levels of patient satisfaction and low rates of complications.

PMID- 9917674
TI  - The transepicondylar axis approximates the optimal flexion axis of the knee.
AB  - The traditional understanding of knee kinematics holds that no single fixed axis
      of rotation exists in the knee. In contrast, a recent hypothesis suggests that
      knee kinematics are better described simply as two simultaneous rotations
      occurring about fixed axes. Knee flexion and extension occurs about an optimal
      flexion axis fixed in the femur, whereas tibial internal and external rotations
      occur about a longitudinal rotation axis fixed in the tibia. No other
      translations or rotations exist. This hypothesis has been tested. Tibiofemoral
      kinematics were measured for 15 cadaveric knees undergoing a realistic
      loadbearing activity (simulated squatting). An optimization technique was used to
      identify the locations of the optimal flexion and longitudinal rotation axes such
      that simultaneous rotations about them could best represent the measured
      kinematics. The optimal flexion axis was compared with the transepicondylar axis
      defined by bony landmarks. The longitudinal rotation axis was found to pass
      through the medial joint compartment. The optimal flexion axis passed through the
      centers of the posterior femoral condyles. No significant difference was found
      between the optimal flexion and transepicondylar axes. To an average accuracy of
      better than 3.4 mm in translation, and 2.9 degrees in orientation, knee
      kinematics were represented successfully by simple rotations about the optimal
      flexion and longitudinal rotation axes. The optimal flexion axis is fixed in the
      femur and can be considered the true flexion axis of the knee. The
      transepicondylar axis axis, which is identified easily by palpation, closely
      approximates the optimal flexion axis.

PMID- 9917675
TI  - Salvage procedures for complex soft tissue defects of the knee.
AB  - The management options for complex soft tissue defects about the knee are varied.
      Limb threatening conditions such as exposure of joint prosthesis or bone requires
      stable coverage to avoid amputation. A study was conducted to review the authors'
      management protocol and experience with complex defects about the knee. A
      retrospective analysis from 1986 to 1996 of 35 patients with complex defects
      about the knee was performed. Treatment options were based on the nature, size,
      location, and depth of the wound. A specific management protocol was applied for
      each patient. Treatments included local wound care, debridement and skin graft,
      fasciocutaneous flap, pedicled muscle flap, and free muscle transfer.
      Postoperatively, patients were evaluated using Knee Society objective and
      functional scores and other instruments to measure outcome. Successful salvage of
      the lower extremity was obtained in 34 (97%) patients. Salvage of the total knee
      prosthesis was obtained in 24 of 29 (83%) patients. Secondary plastic surgery
      procedures were necessary in eight (23%) patients. Secondary orthopaedic
      procedures were necessary in five (15%) patients. No patient required an
      amputation.

PMID- 9917676
TI  - Ultrasound screening for deep venous thrombosis after total knee arthroplasty. 2
      year reassessment.
AB  - The efficacy of ultrasound compared with ascending venography for the detection
      of deep venous thrombosis immediately after total knee arthroplasty was assessed
      after a 2-year interval. One hundred thirty-seven patients were eligible for the
      study; however, 31 patients received only one of the screening methods and a
      color Doppler examination was inconclusive in six patients. Therefore, 100
      patients had a Doppler examination and a venogram. Overall, the sensitivity of
      ultrasound was 85%, the specificity 97%, the positive predictive value 85%, the
      negative predictive value 97%, and the accuracy 95%. The sensitivity in the calf
      was 83%, in the popliteal vein 86%, and in the femoral vein 100%. Two years ago,
      the initial assessment of ultrasound for the detection of deep venous thrombosis
      after surgery in patients who had total joint arthroplasty revealed a 75%
      sensitivity, 99% specificity, 91% positive predictive value, 97% negative
      predictive value, and 97% accuracy. The sensitivity in the calf was 83%; the
      sensitivity in the popliteal vein was 40%; and the sensitivity in the femoral
      vein was 50%. After 2 years of using this screening test with one technician and
      one radiologist, an improvement with this noninvasive technique was shown.
      However, it was found that Doppler imaging is not as sensitive as venography for
      detecting calf thrombi. Any imaging technique should be validated by each
      institution to determine the validity of the instrument and the learning curve of
      the technician administering the examination.

PMID- 9917677
TI  - Patellar component resection in revision and reimplantation total knee
      arthroplasty.
AB  - Between 1979 and 1995, 34 knees in 31 patients had a revision or reimplantation
      total knee arthroplasty in which the patellar component could not be reinserted.
      The patellar bone stock in each of those cases was compromised markedly and
      precluded adequate prosthetic fixation. The mean followup after the revision
      operation was 3.5 years (range, 2-14 years). The Knee Society knee score improved
      from a mean of 59 points preoperatively to a mean of 75 points postoperatively.
      The function score improved from a mean of 46 points preoperatively to a mean of
      69 points postoperatively. Complications occurred in five patients: one patient
      sustained a patellar fracture that required no additional treatment; one
      experienced intermittent episodes of patellar subluxation; one had a recurvatum
      deformity develop and was treated with a brace; one had persistent knee stiffness
      and had four manipulations; and one patient had an extensor lag of 30 degrees
      develop. Twenty-six patients were satisfied with the results of their revision
      operations and five were dissatisfied. Ten patients had persistent knee symptoms
      referable to the patellofemoral articulation: mild pain in three; moderate pain
      in six; and severe pain in one. This study suggests that resection of the
      patellar component during revision or reimplantation total knee arthroplasty may
      be a reasonable approach for patients with markedly compromised patellar bone
      stock; however, mild or moderate anterior knee pain can be expected to persist in
      as much as 1/3 of these patients.

PMID- 9917678
TI  - Revision knee arthroplasty with patella replacement versus bony shell.
AB  - A study was undertaken to assess the clinical results of revision total knee
      arthroplasty in which an unresurfaced bony shell was left after removing a
      patellar component versus those in which a patellar component was implanted.
      Followup was obtained in 123 of 130 consecutive revision total knee replacements
      (94%) from three centers. In 21 knees a shell of patellar bone was left and 92
      knees had a patellar component in place. Ten patients had a patellectomy and were
      excluded from consideration. The group with the bony shell had a lower
      postoperative knee score but the preoperative Knee Society clinical score was
      significantly lower as well in this group of patients. Compared with the group of
      patients with the patellar component in place, the group of patients with knees
      left with a bony shell had a significantly higher percentage of patients who had
      difficulty using stairs, a higher percentage of patients who were not satisfied
      with their surgery, and a higher percentage of patients who rated their surgery
      as unsuccessful in returning them to normal daily activities. When a patellar
      component was not able to be implanted in revision total knee arthroplasty, a
      lower quality result was observed.

PMID- 9917679
TI  - Malrotation causing patellofemoral complications after total knee arthroplasty.
AB  - Thirty patients with isolated patellofemoral complications after total knee
      arthroplasty were compared with 20 patients with well functioning total knee
      replacements without patellofemoral complications. The epicondylar axis and
      tibial tubercle were used as references on computed tomography scans to measure
      quantitatively rotational alignment of the femoral and tibial components. The
      group with patellofemoral complications had excessive combined (tibial plus
      femoral) internal component rotation. This excessive combined internal rotation
      was directly proportional to the severity of the patellofemoral complication.
      Small amounts of combined internal rotation (1 degree-4 degrees) correlated with
      lateral tracking and patellar tilting. Moderate combined internal rotation (3
      degrees-8 degrees) correlated with patellar subluxation. Large amounts of
      combined internal rotational (7 degrees-17 degrees) correlated with early
      patellar dislocation or late patellar prosthesis failure. The control group was
      in combined external rotation (10 degrees-0 degree). The direct correlation of
      combined (femoral and tibial) internal component rotation to the severity of the
      patellofemoral complication suggests that internal component rotation may be the
      predominant cause of patellofemoral complications in patients with normal axial
      alignment. The epicondylar axis and tibial tubercle are reproducible landmarks
      which are visible on computed tomography scans and can be used intraoperatively.
      Using this computed tomography study can determine wether rotational malalignment
      is present and thus, whether revision of one or both components may be indicated.

PMID- 9917680
TI  - Intramedullary pressure and pulmonary function during total knee arthroplasty.
AB  - Twenty-eight patients who underwent unilateral total knee arthroplasty and 20
      patients who underwent simultaneous bilateral total knee arthroplasties
      participated in this study and were randomized to have either a fluted or round
      10-mm diameter femoral intramedullary alignment rod used during surgery. The
      intramedullary rods were cannulated and connected with pressure tubing to a
      monitor which provided measurements of pressure at the tip of each rod. Arterial
      blood gas measurements on room air were obtained before and on the morning after
      surgery. An arterial line was placed and an arterial blood gas measurement was
      obtained at the time of skin incision and again after tourniquet release.
      Pulmonary shunt was calculated from the arterial blood gas measurements.
      Intramedullary pressure during rod insertion was significantly higher for the
      groups of patients having the round compared with the fluted rod. The change in
      pulmonary shunt during surgery was lowest for the patients in the unilateral
      group having the fluted rod and highest for the patients in the bilateral group
      having the round rod. A fluted rather than a round intramedullary alignment rod
      should be used to minimize intramedullary pressure and pulmonary shunting during
      unilateral and bilateral total knee arthroplasties.

PMID- 9917681
TI  - Medial reconstruction during total knee arthroplasty for severe valgus deformity.
AB  - A painful arthritic knee with severe valgus deformity may be treated successfully
      with total knee arthroplasty using several techniques: constrained implant with
      lateral release, nonconstrained implant with lateral release and a thick tibial
      insert, or nonconstrained implant with lateral release and medial reconstruction.
      Eight patients with Type II valgus deformity were treated with nonconstrained
      total knee arthroplasty implants, lateral ITB release at the level of the tibial
      osteotomy, and proximal medial collateral ligament advancement with bone plug
      recession. The reconstruction led to predictably successful outcomes in all
      patients at 4- to 9-years followup. All patients were satisfied with the
      operation. All knees were stable with a functional range of motion at the time of
      last followup.

PMID- 9917682
TI  - The impact of sterilization method on wear in knee arthroplasty.
AB  - Sterilization by gamma irradiation in air has been shown to have the potential to
      accelerate the oxidation of polyethylene components resulting in reduced
      mechanical properties. In the hip, it has been reported that the occurrence of
      delamination and cracking in retrieved bearings is significantly different when
      comparing components sterilized with gamma irradiation in air with components
      sterilized with ethylene oxide. Using a collection of 1635 retrieved polyethylene
      knee bearings, this study pursues a similar comparison of sterilization method
      with clinical wear in the knee. It confirms that retrieved polyethylene knee
      components that were gamma irradiated in air have a high incidence of
      delamination and cracking, leading at times to complete wear through of the
      bearing. Knee components sterilized with ethylene oxide showed no evidence of
      fatigue damage even after in vivo durations in excess of 15 years.

PMID- 9917683
TI  - Long-term effectiveness of translational manipulation for adhesive capsulitis.
AB  - Long term effects of glenohumeral joint translational (gliding) manipulation on
      range of motion, pain, and function in patients with adhesive capsulitis were
      studied. Thirty-one patients underwent brachial plexus block followed by
      translational manipulation of the glenohumeral joint. Changes in range of motion
      and pain were assessed before manipulation with the patient under anesthesia,
      immediately after manipulation with the patient still under anesthesia, at early
      followup (5.3 +/- 3.2 weeks), and at long term followup (14.4 +/- 7.3 months).
      Passive range of motion increased significantly for flexion, abduction, external
      rotation, and internal rotation. Significant decreases in visual analog pain
      scores between initial evaluation and the followup assessments also occurred.
      Furthermore, Wolfgang's criteria score increased significantly between initial
      evaluation and followup assessments. Translational manipulation provides a safe,
      effective treatment option for adhesive capsulitis.

PMID- 9917684
TI  - Proximal femur fractures after free vascularized fibular grafting to the hip.
AB  - The management of symptomatic femoral head osteonecrosis in young, active
      patients is troublesome and controversial. At the authors' institution, 707
      consecutive free vascularized fibular grafts were performed for femoral head
      osteonecrosis between October 1979 and October 1995. Patients who underwent this
      procedure were at increased risk for proximal femur fractures because of the 16
      to 21 mm core drilled through the lateral femoral cortex for removal of the
      avascular bone and placement of the fibular graft. An ongoing prospective
      database of patients who underwent this procedure was accessed to determine the
      incidence of and factors associated with postoperative subtrochanteric femur
      fractures. Eighteen subtrochanteric fractures occurred for an overall incidence
      of 2.5%. All fractures occurred through the core decompression site in the
      lateral femoral cortex. The treatment was nonoperative in seven patients and
      operative in 11. Fourteen of 18 fractures (77%) healed with an average of 4.1
      months until radiographically documented union. Four fractures had nonunions
      develop, three of which later healed with bone grafting and internal fixation,
      whereas the fourth eventually required conversion to total hip arthroplasty.
      Twelve fractures in 251 patients occurred when the weightbearing regimen was
      touchdown weightbearing for the first 6 weeks and five fractures in 456 patients
      occurred when the weightbearing regimen was changed to nonweightbearing. The
      results indicate that nonweightbearing in the immediate postoperative period is
      associated with the lowest fracture rate.

PMID- 9917685
TI  - Intraarticular anatomic variants associated with discoid meniscus in Koreans.
AB  - From July 1990 through June 1994, 106 knees (102 patients) were treated for
      discoid meniscus. Fifteen knees (15 patients) were associated with other
      intraarticular anatomic variants. There were eight knees (8 patients) with
      anomalous insertion of the anterior horn of the medial meniscus into the anterior
      cruciate ligament, and seven knees (7 patients) with anterior expansion of the
      anterior portion of the anterior cruciate ligament below the anterior tibial
      margin. Among the latter, one patient also had anterior transposition of the
      anterior insertion of the medial meniscus, while obliteration of the popliteal
      hiatus was seen in another patient. The discoid menisci were reshaped in 13 knees
      (13 patients), totally resected in one knee, and in one patient the discoid
      meniscus was treated with repair of a peripheral tear and reshaping. Followup
      ranged from 24 to 54 months (average, 37 months) after surgery. The results were
      excellent in eight knees, good in five knees, and fair in two knees as graded
      using the Ikeuchi scale. These anatomic variants, other than the discoid
      meniscus, did not seem to be related to the patient's symptoms.

PMID- 9917686
TI  - Anterior cruciate ligament injury and reconstruction among university students.
AB  - The consequences of athletic injuries extend beyond the musculoskeletal system.
      Depression, anger, and tension have been observed in athletes with athletic
      injuries. It was hypothesized that among student athletes, the psychologic impact
      of injury may be seen as a drop in academic performance. Thirty-eight students
      who had an anterior cruciate ligament injury and subsequent reconstruction were
      evaluated retrospectively by academic transcript and questionnaire to measure
      their academic performance before their injury, in the semester of their injury,
      and in the semester after their surgery. The patients were compared with randomly
      selected undergraduate control subjects. To evaluate any effect of the timing of
      the surgery on academic performance, the patients were separated into two groups,
      according to the timing of their reconstruction: those who had surgery during the
      academic semester, and those who elected to wait for a school break. There was a
      significant drop in grade point average of 0.3 grade points during the semester
      of injury among all injured students. Compared with those who had surgery during
      a break, the students who had surgery during the semester received more
      frequently the grade of failure (6% versus 0%) or incomplete (33% versus 9%).
      These students also missed more school days (10.5 days versus 1.5 days) and
      examinations (2.2 examinations versus 0.1 examinations). Only 47% of students who
      had surgery during the semester were satisfied with their decision for surgical
      timing, compared with 96% satisfied with the timing during an academic break.
      Acute anterior cruciate ligament rupture, and surgical reconstruction during an
      academic semester, have a significant academic effect in university students.

PMID- 9917687
TI  - Biodegradable rods in adult osteochondritis dissecans of the knee.
AB  - Symptomatic osteochondritis dissecans of the knee in skeletally mature patients
      does not follow a predictable natural history and there has been a trend toward
      internal fixation of the unstable fragment(s) where possible. Biodegradable
      implants are enticing for intraarticular use: implant removal is unnecessary and
      its degradation potentially allows a gradual shift of loading stress to the
      fracture site. Nine patients with a mean age of 18.6 years (range, 14-23 years)
      deemed skeletally mature by plain film radiography underwent internal fixation of
      fragments by 2-mm self reinforced polylactic rods. Six procedures were completed
      arthroscopically and three required arthrotomy. All fragments were of the medial
      femoral condyle. The procedure was tolerated well although three patients had
      early postoperative serosanguinous effusions develop that did not recur after one
      aspiration. At a mean followup of 33 months (range, 24-54 months), eight
      fragments radiographically were united whereas one remained ununited at 26
      months, accounting for the one poor result in this series. Seven patients had
      good to excellent results according to Hughston's criteria and were satisfied
      with the procedure. One of these seven patients had a spontaneous effusion
      develop at 5 months that did not recur after aspiration and intraarticular
      steroid injection. Severe, unremitting synovitis did not occur in any patient.
      Internal fixation of osteochondritis dissecans of the knee with biodegradable
      polylactic rods provided satisfactory control of symptoms in the short term and
      resulted in radiographically stable lesions in eight of nine patients. These rods
      may be suited best for fragmented lesions with intact articular cartilage as an
      adjunct to drilling.

PMID- 9917688
TI  - Salvage of failed femoral megaprostheses with allograft prosthesis composites.
AB  - The records of 11 consecutive adult patients who underwent revision of a failed
      femoral megaprosthesis (aseptic loosening, nine; periprosthetic fracture, one;
      and prosthesis fracture, one) to an allograft prosthesis composite were reviewed
      retrospectively. Complications included radiographic component subsidence in two
      patients (18%), hip instability in three patients (27%), deep infection in two
      patients (18%), and allograft fractures in two patients (18%). Five patients
      (45%) required subsequent reoperations; four patients underwent removal of the
      allograft prosthesis composite at a mean of 16 months (range, 5-41 months) and
      one patient (9%) with hip instability underwent revision of the failed
      megaprosthesis to a constrained acetabulum. Reconstruction of a failed femoral
      megaprosthesis is a complex problem caused by extensive bone loss and violation
      of soft tissue attachments. Despite a high complication rate, six patients (55%)
      remained ambulatory and had mild or no pain at a mean followup exceeding 5.5
      years.

PMID- 9917689
TI  - Small wire external fixation of high energy tibial plateau fractures.
AB  - Open plate osteosynthesis for high energy tibial plateau fractures with
      dissociation between the metaphysis and diaphysis has been plagued with frequent
      soft tissue complications. The Harbor-University of California at Los Angeles
      Medical Center's experience with small wire external fixation supplemented by
      limited internal fixation is examined. This alternative method of adequate stable
      fixation offers the advantage of minimal soft tissue compromise. Twenty-four
      patients with Schatzker Type VI tibial fractures were treated with small wire
      external fixation. Supplementary limited internal fixation was used with
      percutaneous screws in 10 patients and with open reduction in one patient.
      Sixteen patients had isolated fractures, and eight others suffered multiple
      injuries. Minimum followup was 12 months. All fractures healed. Complications
      included one septic knee, two infections at screw sites, and one 10 degrees knee
      flexion contracture. One knee had Grade 3 radiographic arthrosis, five had Grade
      2, 10 had Grade 1, and eight showed no arthrosis. The outcomes (Knee Society
      clinical rating system) of this study compare favorably with outcomes described
      in reports published previously for this type of fracture, despite inclusion of
      eight multiply injured patients. This technique preserves the goals of early
      range of motion and stable fixation for these devastating injuries, while
      decreasing the observed major wound complications and nonunion rates. However,
      longer followup may reveal higher arthrosis rates, specifically in those
      fractures that were not anatomically reduced.

PMID- 9917690
TI  - In vitro effects of holmium. YAG laser on caprine stifle retinacular restraints.
AB  - This study was designed to evaluate the efficacy of the Holmium:YAG laser for
      performing lateral release and medial joint capsular tightening intracapsularly
      and to compare the efficacy of the laser versus a scalpel blade for performing a
      lateral release by performing arthroscopic surgery on 29 caprine patellofemoral
      joints. Specimens were divided into six treatment groups and treatments consisted
      of lateral release alone, medial capsular tightening alone, or both treatments,
      and the effect of each treatment on patellar tracking was evaluated using video
      analysis of optical markers. Each treatment caused significantly different
      magnitudes of medial patellar displacement throughout a 75 degrees range of
      motion: medial tightening followed by lateral release (1.5 +/- 0.10 mm, mean +/-
      standard error of the mean); lateral release followed by medial tightening (1.1
      +/- 0.11 mm); medial tightening alone (0.73 +/- 0.10 mm); lateral release alone
      (0.36 +/- 0.09 mm); and sham (-0.15 +/- 0.05 mm). There were no significant
      differences between performing the lateral release using the laser (1.5 +/- 0.10
      mm) versus a scalpel (1.4 +/- 0.11 mm). This study shows that lateral release can
      be performed as effectively with the laser as with a scalpel and that the laser
      is an effective tool for performing lateral release and medial joint capsular
      tightening procedures intracapsularly in this caprine model.

PMID- 9917691
TI  - Compartment syndrome. An unusual etiology.

PMID- 9917693
TI  - Use of allogeneic transfusions.

PMID- 9917692
TI  - Ensuring the success of women in academic orthopaedics.
AB  - In spring of 1995, the Academic Orthopaedic Society convened a panel of 21 female
      academic orthopaedists and 24 senior members of the society to discuss the
      challenges facing female orthopaedic residents and women in academic
      orthopaedics. Participants began by reviewing results of a 200 item mail survey
      of fulltime and parttime female academic orthopaedic surgeons. The survey had
      been conducted in early 1995. Using the Delphi technique, the panelists
      identified challenges facing women and ranked them in priority order. Although
      the challenges identified by survey respondents and panelists were similar, the
      priority assigned to them varied. Panel and survey findings pointed to a need for
      action in six areas: increasing mentoring; overcoming gender bias; reducing
      women's social and professional isolation; increasing attention to promotion and
      salary equity; providing greater accommodation for family responsibilities; and
      expanding recruitment efforts. This paper suggests actions that department
      chairpersons and the Academic Orthopaedic Society may take to attract more women
      to academic orthopaedics. Because many of the issues emerging from the survey and
      panel were not gender specific, implementation of the recommendations may benefit
      male and female orthopaedic residents and academic surgeons in general.

PMID- 9917694
TI  - Autotransfusion.

PMID- 9917695
TI  - Safety of the blood supply.
AB  - Three of four recipients of transfusion in the United States are patients
      undergoing surgery, and despite promising advances in the development of
      alternatives to allogeneic blood transfusion, it is likely that for years to come
      this patient population will remain dependent on blood donated by volunteers. The
      safety of the blood supply has been questioned seriously since it became known
      that the human immunodeficiency virus could be transmitted by transfusion. In
      response to this threat, enforcement of strict donor eligibility criteria,
      removal of high risk donors from the donor pool, and testing of each donation
      with a panel of viral markers were instituted which have reduced the infectious
      risks of allogeneic blood transfusion dramatically during the last decade. The
      current safety of the blood supply is reviewed and the ongoing efforts to improve
      the safety of transfusions in the future are summarized briefly.

PMID- 9917696
TI  - Anemia in the patient undergoing surgery and the transfusion decision. A review.
AB  - The heightened awareness of the problems of transfusion reactions, disease
      transmission, and potential immunosuppression has led surgeons to reevaluate
      their reasons for transfusion. Current practice policies recommend that elective
      transfusion of allogeneic blood be avoided whenever possible in patients having
      surgery. If patients are to have appropriate transfusion, the basic
      pathophysiology and clinical response of the patient to anemia must be
      understood. This article reviews the physiologic response to anemia in the
      patient having surgery and explores the components of the decision to use
      transfusion.

PMID- 9917697
TI  - In search of the transfusion trigger.
AB  - Red blood cell transfusions are used commonly in orthopaedic surgery and cost
      billions of dollars annually. The goals of transfusion are to reduce mortality
      and morbidity and improve functional status that result from anemia and
      inadequate O2 delivery. Risks of infections from transfusion are low and continue
      to decline, but evidence is growing that red cell transfusions are
      immunosuppressive and predispose patients to postoperative infections. However,
      there actually are very little data on when transfusion is indicated.
      Observational data suggest that transfusion does not reduce mortality in patients
      with preoperative or postoperative hemoglobin levels 8 g/dL or greater, although
      no conclusions could be drawn about the effect of transfusion in patients with
      hemoglobin 8 g/dL or less. Large, well performed randomized clinical trials are
      needed to establish the efficacy of transfusion. Until better data are available,
      orthopaedic surgeons will have to rely on clinical judgement in decisions
      regarding transfusions. Using a higher transfusion threshold in patients with
      cardiovascular disease is recommended.

PMID- 9917698
TI  - An algorithm to optimize perioperative blood management in surgery.
AB  - Innovation in surgical blood management has been fueled by patients' perceptions
      of the risks associated with allogeneic blood transfusions and by surgeons'
      attitudes toward the use of allogeneic blood. The challenge is to determine the
      best blood management strategy to implement in the individual patient,
      particularly in patients with anemia who are at high risk of allogeneic blood
      transfusion. An algorithm to estimate safe blood loss based on individual patient
      parameters has been developed. The algorithm uses patient weight, gender, and
      preoperative hematocrit level to derive the volume of blood loss that can be
      tolerated while maintaining a target postoperative hematocrit level. Because the
      margin of safe blood loss can be anticipated, the most appropriate blood
      conservation option(s) can be implemented and perioperative blood management can
      be optimized.

PMID- 9917699
TI  - Global blood management in orthopaedic surgery.
AB  - Blood loss tends to be significant in many orthopaedic procedures because of the
      nature of the tissues and the inability to cauterize or coagulate bleeding bony
      surfaces. Regional hypotensive anesthesia has been useful in reducing blood loss
      particularly for joint replacement. A spectrum of measures is available to
      retrieve autologous blood and reinfuse it. The loop consists of predeposit
      autologous blood, preoperative hemodilution, intraoperative and postoperative red
      cell retrieval, and reinfusion. The safety of autologous blood has been accepted
      universally, but the measures to preserve it must be used judiciously to avoid
      excessive cost and, most importantly, ensure patient safety.

PMID- 9917700
TI  - Predictors of transfusion risk in elective knee surgery.
AB  - Two hundred seventy-nine patients undergoing primary unilateral total knee
      replacement and 280 patients undergoing primary bilateral total knee replacements
      were reviewed retrospectively. Patients' height, weight, hemoglobin level before
      donation, hemoglobin level before surgery, autologous donation, number and type
      of transfusions whether autologous or allogeneic, and hemoglobin at discharge
      were collected from hospital and clinic records. The average drop in hemoglobin
      was 3.85 g/dL in the group of patients undergoing unilateral total knee
      replacement and 5.42 g/dL in the group of patients undergoing bilateral total
      knee replacements. The preoperative hemoglobin and blood volume seemed to be very
      strong, statistically significant predictors of transfusion risk in single and
      bilateral knee replacements. In unilateral total knee replacement, patients with
      a hemoglobin of greater than 13 g/dL had only an 8% chance of transfusion and if
      they donated autologous blood, 66% of the blood was wasted. Preoperative anemia
      was a strong predictor of transfusion risk in patients undergoing unilateral and
      bilateral total knee replacements and carried a very high allogeneic transfusion
      exposure risk, even in patients who had donated blood preoperatively. A nomogram
      was developed using blood volume and predonation hemoglobin to predict
      transfusion risk and need to predeposit autologous blood in patients undergoing
      unilateral and bilateral total knee replacements.

PMID- 9917701
TI  - Epoetin alfa. A bloodless approach for the treatment of perioperative anemia.
AB  - Under normal physiologic conditions the level of circulating red blood cells is
      regulated precisely by the glycoprotein erythropoietin. In major elective
      surgery, patients who are participating in preoperative autologous blood donation
      or who are anemic may not have the capacity to manufacture sufficient red blood
      cells in response to increases in endogenous erythropoietin that is sufficient to
      avoid perioperative allogeneic blood transfusion. In these patients pharmacologic
      doses of recombinant human erythropoietin (Epoetin alfa) have been shown to
      accelerate erythropoiesis, thereby increasing preoperative red blood cell
      production, hematocrit level, and hemoglobin concentration and reducing exposure
      to allogeneic blood transfusion. In four large multicenter studies, 869 patients
      undergoing major elective surgery were treated with a daily regimen (300 or 100
      IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous
      Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although
      all Epoetin alfa regimens were effective at accelerating erythropoiesis and
      increasing red blood cell production, the weekly regimen was the most patient
      friendly, cost effective regimen for treating preoperative anemia and minimizing
      patient risk of allogeneic blood transfusion.

PMID- 9917702
TI  - Blood conservation in hip trauma.
AB  - Patients with hip or pelvic fractures experience significant blood loss as a
      result of the fracture and from the surgery that subsequently is performed. The
      emergent and unplanned nature of fracture surgery precludes the use of
      preoperative blood donation and the optimization of chronic medical problems.
      Blood transfusion frequently is required to maintain adequate tissue O2 delivery
      in these injured patients. However, the administration of allogeneic blood causes
      other problems, including a well documented increase in the risk of infectious
      complications. Perioperative measures to minimize blood loss such as hypotensive
      anesthesia and red blood cell salvage are important, but often are inadequate to
      prevent the need for blood transfusion. Recently, erythropoietin therapy has been
      shown to stimulate hematopoiesis in patients with hip fractures. The authors
      discuss their experience with blood loss management in these patients with hip
      injuries, including aggressive Fe replacement therapy and the use of recombinant
      human erythropoietin.

PMID- 9917703
TI  - Acute normovolemic hemodilution.
AB  - Acute normovolemic hemodilution was described to be useful as a blood
      conservation strategy more than 25 years ago, yet seldom is practiced today. The
      benefit of acute normovolemic hemodilution is perceived to be modest and the
      technique is not taught in anesthesia or surgery training programs. Acute
      normovolemic hemodilution is an autologous blood procurement strategy that is
      superior to the predeposit of autologous blood for several reasons: Acute
      normovolemic hemodilution is less costly, with an average cost of $25 per unit
      compared with $175 per unit predonated; and acute normovolemic hemodilution units
      are reinfused to patients before the patient leaves the operating room, so that
      the units need not be tested and there is no possibility of administrative error.
      Emerging clinical studies now show that acute normovolemic hemodilution is
      equivalent to predonated autologous blood in reducing allogeneic blood exposure
      in patients undergoing elective surgery.

PMID- 9917704
TI  - Erythropoietin therapy in the perioperative setting.
AB  - Recombinant human erythropoietin has been approved for use in patients undergoing
      autologous donation in Japan, Europe, and Canada since 1993, 1994, and 1996,
      respectively, and for perisurgical adjuvant therapy without autologous donation
      in Canada and the United States since 1996. Early clinical trials of
      erythropoietin therapy in the setting of autologous donation have provided
      important information regarding clinical safety, erythropoietin dose, and
      erythropoietic response. Later trials of perisurgical erythropoietin therapy
      without autologous donation provided data on efficacy (reduced allogeneic blood
      exposure) that led to approval of erythropoietin in patients undergoing surgery.
      However, the erythropoietin doses (300 U/kg subcutaneous x14 days) used in these
      trials, and their subsequent inclusion in labeling for the use of this product,
      are costly and tedious to administer. A recent study reported that a weekly
      regimen of erythropoietin (600 U/kg) for 4 weeks is less costly but just as
      effective at reducing allogeneic blood exposure in elective orthopaedic surgery.
      The most cost effective regimen that has been shown to minimize allogeneic
      exposure is preoperative erythropoietin therapy (600 U/kg subcutaneous weekly x2
      and 300 U/kg subcutaneous on day of surgery) coupled with acute normovolemic
      hemodilution in patients undergoing radical retropubic prostatectomy. A similar
      regimen of erythropoietin therapy in patients undergoing coronary artery bypass
      grafting (2500 U/kg subcutaneous in divided doses for 2 weeks preoperatively)
      coupled with hemodilution also was effective. Low dose erythropoietin therapy
      coupled with acute normovolemic hemodilution ultimately may be shown to be cost
      equivalent to the predonation of three autologous blood units before elective
      surgery.

PMID- 9917705
TI  - Oxygen carriers as blood substitutes. Past, present, and future.
AB  - Prospects for safe and effective blood substitutes are promising, based on
      clinical trial results of soluble hemoglobin solutions and emulsion of
      perfluorocarbins. Advantages of blood substitutes include sterilization of viral
      and bacterial contaminants, room temperature storage, a long shelf life, and
      absence of ABO and other red cell antigens. Projected arenas for their use
      include not only military applications but also trauma medicine and elective
      surgical settings, coupled with acute normovolemic hemodilution. Applications of
      perfluorocarbons are limited by the need for 100% FIO2. A significant challenge
      facing development of hemoglobin solutions is their effect on vascular tone
      through smooth muscle constriction. Development of second or third generation
      hemoglobin solutions may be necessary so that hemoglobin solutions more closely
      mimic cellular hemoglobin's nitric oxide binding properties. Optimizing O2
      delivery to ischemic tissues and organs may lead to regulatory approval of these
      agents in this setting before their approval as blood substitutes.

PMID- 9917706
TI  - Prospectus. Future trends in transfusion.
AB  - There are several emerging trends in perioperative transfusion that are promising
      in terms of clinical practice. These include modifications in transfusion
      practice, changes in blood bank procedures and philosophy, the use of autologous
      transfusion methods, and the development of new artificial blood substitutes.
      Refinement of current techniques will continue, and will be driven by several
      factors. The most significant recent changes in surgical practice relating to
      blood transfusion include a decreased reliance on the use of arbitrary
      transfusion triggers, and the increased use of various forms of autologous
      transfusion. Other clinical changes have been less obvious, such as changes in
      blood bank management practice. Similar factors drive the development of blood
      conservation strategies and artificial blood substitutes or O2 carriers. Both
      will play a role in reducing perioperative blood loss. The most likely scenarios
      involve use of blood substitutes in conjunction with various methods of blood
      conservation. Recent advances in blood banking have made the donor blood supply
      safer than ever before. Progress in the clinical setting and in the laboratory
      have widened the possibilities for treatment of perioperative blood loss, with
      attention to minimizing risk and cost, and maintaining safety for the patient.

PMID- 9917707
TI  - Reconstruction of the shoulder joint using an acetabular allograft. A report of
      two cases.
AB  - Wide resection of tumors involving the glenoid region of the scapula compromises
      a center of motion in the shoulder joint and can cause significant loss of
      function. Two patients with aggressive tumor of the scapula were treated with
      wide resection and reconstruction using an osteoarticular acetabular allograft.
      The ball and socket geometry of the newly reconstructed joint and secure
      reattachment of soft tissues in the allograft provided a stable shoulder joint.
      The functional results of the two patients were 87% and 93%, respectively
      according to the Musculoskeletal Tumor Society system. In a select group of
      patients with locally aggressive lesions of the scapula, a surgical
      reconstruction with an osteoarticular allograft would yield satisfactory
      functional and cosmetic results.

PMID- 9917708
TI  - Diabetic Charcot's arthropathy of the wrist. Case report and literature review.
AB  - Charcot's arthropathy of the right wrist in a 55-year-old patient with diabetes
      is reported. Neurogenic arthropathy rarely affects non-weightbearing joints such
      as those of the hand and wrist; the foot, ankle, and knee most commonly are
      affected. When crutches are used by patients with diabetes who have Charcot's
      arthropathy, orthotics and platform crutches can help to relieve pressure induced
      by weight transfer to the wrist during ambulation.

PMID- 9917709
TI  - Femoral head osteonecrosis after bone marrow transplantation.
AB  - Thirty-five patients with bilateral osteonecrosis of the femoral head after bone
      marrow transplantation were reviewed retrospectively. The median age at the time
      of transplantation was 26 years. The first symptoms occurred within 2 years of
      transplantation. At presentation, 18 of the patients reported pain in both hips,
      17 had symmetric radiographic lesions, and 39 of the hips had collapsed. Medical
      treatment was indicated initially. At the final examination before surgery
      (median, 3.5 years), 31 patients had bilateral hip pain, 22 patients had
      symmetric radiographic lesions, and 56 of the hips had collapsed. Fifty-seven of
      the hips required surgery, including one open drainage, four core decompressions,
      six cup arthroplasties, and 46 primary total hip replacements. Six hips (four
      core decompressions; two cups) later underwent total hip replacement revision,
      and a deep infection developed in one. By considering the requirement of a total
      hip replacement as a failure of conservative treatment, the rate of survival of
      the femoral head was 30% 5 years after the transplant. There was no significant
      difference between the Ficat grades, except for Grade 0, which showed a higher
      survival rate. The study of the specific features of the osteonecrosis may lead
      to the recommendation of primary total hip arthroplasty after failure of the
      medical treatment.

PMID- 9917710
TI  - Reconstruction of chronic rupture of the extensor mechanism after patellectomy.
AB  - Chronic extensor mechanism ruptures are uncommon but challenging clinical
      problems. Previously published procedures for treating chronic extensor mechanism
      ruptures assume an intact patella is available to anchor the repair. A case is
      presented of a patient who had a previous patellectomy, followed by rupture of
      the extensor mechanism. After two failed attempts at repair, an Achilles tendon
      allograft was used successfully to restore function of the extensor mechanism.
      The described technique offers an alternative for reconstruction of the extensor
      mechanism after patellectomy.

PMID- 9917712
TI  - Radiologic and histologic analysis of morselized allograft in revision total knee
      replacement.
AB  - Morselized cancellous allograft was used to fill large femoral and/or tibial
      defects in 63 patients (63 knees) who had revision surgery for failed
      arthroplasty between September 1988 and January 1993. Firm seating of the
      components on a rim of viable bone and rigid fixation with a medullary stem were
      achieved in all cases. One patient was lost to followup, leaving 62 patients with
      standard radiographic evaluation at 1 month, 3 months, and yearly intervals
      postoperatively. Fourteen patients required reoperation between 3 weeks and 37
      months after revision surgery for loosening (two patients), wound avulsion (one
      patient), wound hematoma (two patients), painful wires (four patients), patellar
      tendon avulsion from the tibial tubercle (two patients), patellar subluxation
      (one patient), or late onset instability (two patients). A biopsy specimen was
      taken from the central portion of the allograft in each case. Evidence of
      healing, bone maturation, and formation of trabeculae was seen in all allografted
      areas visible on radiograph at 1 year after surgery. No sign of significant bone
      graft loss had occurred in any case. Likewise, all biopsy specimens, including
      the 3-week specimen, showed evidence of active new bone formation in the
      allografted area. Active bone formation was found in and around the allograft
      pieces, and new osteoid formed directly on dead allograft trabeculae. Vascular
      stroma was present between the bone fragments deep in the allograft mass. Older
      biopsy specimens evidenced progressive maturation, and evidence of active
      osteoclastic activity was absent by 18 months after surgery. All patients but one
      had significant improvement in their pain score as compared with their
      preoperative status. Although the complication rate was high (22%), all but one
      patient achieved lasting fixation to bone, adequate ligament balancing, good
      range of motion, and minimal to mild pain. Two patients required revision
      surgery. Both had greatly improved bone stock so that new implants could be
      applied with minor additional grafting. This method of bone stock reconstitution
      appears to be reliable when used in conjunction with firm rim seating and rigid
      intramedullary stem fixation.

PMID- 9917711
TI  - The effect of immediate weightbearing after anterior cruciate ligament
      reconstruction.
AB  - Immediate weightbearing has been advocated after anterior cruciate ligament
      reconstruction and is thought to enhance the return of quadriceps muscle activity
      and knee extension range of motion without jeopardizing graft integrity. This
      study examined the effect of immediate weightbearing after anterior cruciate
      ligament reconstruction on the return of vastus medialis oblique electromyography
      activity, knee extension range of motion, knee stability, physical examination,
      Lysholm score, and anterior knee pain. Forty-nine patients (24 men and 25 women)
      undergoing endoscopic central third patella tendon autograft reconstruction were
      randomized prospectively into two groups. Group 1 patients underwent immediate
      weightbearing as tolerated. Group 2 patients were kept nonweightbearing for 2
      weeks. All measurements were taken before surgery, 2 weeks after surgery, and
      between 6 and 14 months (average, 7.3 months) followup. There was no effect of
      weightbearing on knee extension range of motion or vastus medialis oblique
      function at followup. In addition, knee stability was not compromised after
      surgery. Seven of 20 (35%) nonweightbearing patients and only two of 25 (8%)
      immediate weightbearing patients reported anterior knee pain at followup.
      Overall, immediate weightbearing did not compromise knee joint stability and
      resulted in a better outcome with a decreased incidence of anterior knee pain.

PMID- 9917713
TI  - Use of extendable total femoral replacements in children with malignant bone
      tumors.
AB  - Although rarely required, extendable reconstruction devices for replacing the
      entire femur offer children with malignant bone tumors the opportunity of a
      nearly normal development by overcoming an expected leg length discrepancy.
      Femoral integrity can be restored, allowing most patients to walk without the use
      of aids. There are no data available to provide evidence regarding long term
      results and morbidity in such patients. Six patients (range 2-12 years of age),
      three with osteogenic osteosarcoma and three with Ewing's sarcoma, were treated
      between 1988 and 1996 with custom made Stanmore extendable prosthetic total
      femoral replacements. One patient died 12 months after surgery because of
      complications relating to pulmonary metastasis. The remaining five patients were
      observed between 2.7 and 8.9 years (average, 5 years). No tumor recurrence has
      been recorded and no amputation has been performed. All surviving patients
      underwent an average of 9.4 operative procedures (range, 4-16 procedures)
      including 6.4 extension procedures (range, 3-10 procedures), and one prosthetic
      revision (range, 0-3 procedures). Five revisions in two patients were necessary
      because of infection, loosening of the prosthesis, mismatch between femoral head
      and acetabulum, or full extension of the extending mechanism. The functional
      results were measured in accordance with the Musculoskeletal Tumor Society rating
      score, with an average result of 77.3%. Total femoral replacement in a growing
      individual achieves good functional results yet has various risks for an
      uncertain outcome. Careful selection of the patient and realistic appraisal of
      the long term prospects are essential for successful treatment.

PMID- 9917714
TI  - Multiple neurilemomas. A case report.
AB  - Multiple neurilemomas in diverse locations of the body developed in a 53-year-old
      woman. The patient had multiple neurilemomas which occurred in the thoracic
      spine, lumbar spine, retroperitoneal sympathetic chain, sacral nerve root,
      femoral nerve, both sciatic nerves, radial nerve, and ulnar nerve without
      evidence of Von Recklinghausen's disease. This is the first well documented
      report on multiple neurilemomas with whole body distribution.

PMID- 9917715
TI  - Ewing's sarcoma masquerading as osteomyelitis.
AB  - Ewing's sarcoma in the infant and young child is rare, highly malignant, and can
      be difficult to identify. An erroneous diagnosis of osteomyelitis may be
      considered first because the presentation may be similar to that of Ewing's
      sarcoma, and routine laboratory evaluation may not distinguish between these
      entities. Two such cases are presented, one involving the tibia in a 16-month-old
      child and another a finger phalanx in a 7-month-old child. In both cases the
      correct diagnosis of Ewing's sarcoma was delayed because of initial misdiagnosis
      of osteomyelitis. This diagnostic dilemma is summarized, and the literature
      reviewed. Special attention is given to recent advances in histochemistry and
      cytogenetics that assist in tumor identification. The conclusion highlights areas
      of remaining controversies for which additional study may facilitate distinction
      between osteomyelitis and Ewing's sarcoma.

PMID- 9917716
TI  - Overgrowth and outcome after femoral shaft fracture in children younger than 2
      years.
AB  - Twenty-one children younger than 2 years with a fractured femur were evaluated
      retrospectively to determine limb overgrowth, efficacy, and outcome after
      treatment with immediate spica casting. All children had spica casts placed
      without general anesthesia within 24 hours of admission. Followup averaged 51
      months (range, 24-110 months). Average shortening in the spica cast at initial
      application was 0.5 cm (range, 0-1.8 cm). The average length of hospitalization
      was 2.2 days. Three patients went home the same day, and seven were discharged
      after a single overnight stay in the hospital. No patients underwent closed
      manipulation or a cast change for malalignment of the fracture. Child abuse was
      identified as the mechanism of injury in eight of 12 (67%) children younger than
      1 year of age and in only one of nine (11%) children between 1 and 2 years of
      age. Leg lengths were determined by measurement with tape and graduated blocks.
      At followup, the average limb length inequality was 0 cm, with an average net
      growth of 0.5 cm (range, -0.5-1.8 cm). Only one child had a limb length
      inequality of more than 1 cm as measured with tape (20 months of age), and no
      child had a limb length inequality of more than 1 cm as measured with blocks. No
      child or parent reported any residual pain, limp, or limitation of activity. The
      results of this study suggest that overgrowth does occur in children younger than
      2 years. Additionally, immediate spica casting with early discharge to home is
      associated with few complications, no functional limitations, and minimal limb
      length inequality.

PMID- 9917717
TI  - Biodegradable interlocking nails for fracture fixation.
AB  - Serious problems such as stress shielding, allergic reactions, and corrosion are
      associated with the use of metallic fracture fixation devices in fractured long
      bones. Metal implants often are removed during a second retrieval operation after
      fracture healing has completed. A biocompatible implant that degrades slowly
      during implantation would obviate the need for a second operation and save the
      patient from considerable physical, psychologic, and financial discomfort. The
      biodegradable implant must provide the fractured limb sufficient support for a
      certain time, allowing early loading. A gradual transfer of load from the
      biodegradable implant to the bone would result in a better product of bone
      healing and avoid stress shielding. In an animal model using adult sheep, two
      types of biodegradable polymer interlocking nails were tested in comparison with
      a stainless steel interlocking nail. Fracture healing, mechanical properties of
      the bones, degradation behavior in vivo and in vitro, and tissue response were
      monitored during a 2 1/2-year followup study. To detect shifts in acid base
      relations caused by the release of acid compounds, pH measurements were
      performed. Fracture healing was unimpaired, and the mechanical test results of
      all three groups were excellent. Histologic analysis showed a mild inflammatory
      response, but no pH shifts were observed. The results of this study justify
      additional research on these promising materials.

PMID- 9917718
TI  - Quantitative analysis of collagen fibrils of human cruciate and meniscofemoral
      ligaments.
AB  - The ultrastructural anatomy of collagen fibril diameters in the cruciate and
      meniscofemoral ligaments, from four young human cadaver knees (mean age, 20
      years, range, 17-22 years) was studied using transmission electron microscopy.
      Samples were harvested from the proximal, middle, and distal regions of the
      anterior and posterior cruciate ligaments, and the meniscofemoral ligament.
      Photomicrographs were taken and assessed quantitatively using image analysis
      software to determine the collagen fibril diameters and eccentricities, and the
      percentage of total cross sectional area occupied by collagen. The collagen
      fibril diameter for the anterior cruciate ligament was found to be largest in the
      distal region but it decreased as it moved proximally. The posterior cruciate
      ligament had an opposite trend because it decreased from the proximal to the
      distal region. For the meniscofemoral ligament, the fibrils of the middle region
      were larger than those of the proximal and distal regions. The percentage of
      total cross sectional area occupied by collagen, however, did not vary
      significantly between regions. Fibril eccentricity also varied little between
      ligament or location. The variability observed in fibril diameters may account
      for the different mechanical properties of the ligaments.

PMID- 9917719
TI  - A comparative evaluation of halo pin designs in an immature skull model.
AB  - To design an improved halo pin for use in pediatric patients, three commonly used
      halo pins were evaluated with a mechanical testing apparatus and segments of
      prepared fetal calf skull. The pins were driven through the bone segments while
      the load at the bone-pin interface was measured. New pins were designed with
      respect to pin tip and flange width and similarly compared. Mean maximum loads to
      penetration, normalized for bone segment thickness, were 55.6 N/mm for the PMT
      Corporation pin, 61.5 N/mm for the Bremer pin, and 73.6 N/mm for the Ace pin.
      Four new, short tipped pins were designed and compared with the Ace pin, and
      there was no significant difference. Finally, four new pins were designed with
      varying flange widths. Mean maximum loads, normalized for bone segment thickness,
      were 68.9 N/mm for the 4.2 mm flange, 72.2 N/mm for the 4.7 mm flange, 92.9 N/mm
      for the 5.2 mm flange, and 96.4 N/mm for the 5.7 mm flange. The findings of this
      investigation are clinically important because they may help to explain the
      variability in the complication rates seen with the use of different halo systems
      in children. The three halo pins currently on the market have different pin
      designs, including tip lengths and flange distances, which contribute to the
      difference in load to penetration for each pin. The new, wide flanged, short
      tipped halo pin design might decrease the complication rate of halo use in
      children by providing an improved capacity to resist penetration despite
      increased loads of application.

PMID- 9917720
TI  - Osteoinduction of human demineralized bone: characterization in a rat model.
AB  - The increasing clinical use of human demineralized bone matrix has brought about
      the desire to understand better the osteoinductivity of these graft materials.
      The rat heterotopic model has been used successfully to show the sequence of
      events involved in the endochondral ossification process resulting in
      osteoinduction. In this study, the osteoinductive potential of human
      demineralized bone powder was assessed, using immune compromised rats (athymic
      rnu/rnu) to avoid problems associated with cross species incompatibilities.
      Implants were placed in subcutaneous or intermuscular sites. This model is
      characterized to provide a basis for routinely determining the performance of
      human demineralized bone powder. Demineralized bone powder was prepared from rat
      and human cortical bone according to a strict protocol. The lack of response to
      guanidine HCl extracted (noninductive) demineralized bone showed the selectivity
      of the assay. The same lots of human and rat demineralized bone were tested in
      sequential experiments during a 1-year period. These results showed reproducible
      induction of the demineralized bone powder between experiments. Combining
      demineralized bone with the guanidine HCl extracted demineralized bone in varying
      ratios tested the sensitivity of the assay. These results showed an increase in
      bone formation with increasing quantities of active demineralized bone and
      established the ability of the bioassay to differentiate between the various
      levels of active (osteoinductive) demineralized bone powder. With this model,
      consistent performance of demineralized bone powder processed by well controlled
      methods was seen.

PMID- 9917721
TI  - Etiology of idiopathic scoliosis. Computational study.
AB  - A review of the literature on the mechanical aspects of the etiology for
      idiopathic scoliosis reveals that the buckling hypothesis has been presented as a
      purely mechanical phenomenon. In an attempt to confirm the buckling hypothesis, a
      numerical simulation of growth and the resulting buckling phenomena was done by
      means of finite element analysis. It previously was observed that growth was
      induced in the T4 to T10 vertebrae. Only the sacrum was assumed to be stationary.
      From the growth analysis, a deformation process that mitigated thoracic kyphosis
      was obtained as observed in healthy children during early adolescence. From the
      buckling analysis, the first to the fourth buckling modes that correspond to the
      first side bending, first forward bending, first rotation, and second side
      bending modes were obtained. The shape of the fourth buckling mode (second side
      bending mode) was in good agreement with the clinical shape. Considering the
      potential for controlling these modes by posture change, it is concluded that the
      second bending mode in the coronal plane is one of the most likely etiologic
      candidates in the mechanics of thoracic idiopathic scoliosis.

PMID- 9917722
TI  - Biomechanical and densitometric bone properties after callus distraction in
      sheep.
AB  - Assessment of biomechanical stability of diaphyseal bone lengthened by callus
      distraction is an unsolved problem. A middiaphyseal corticotomy was performed in
      the left tibia of 24 sheep. After 7 days, callus distraction was begun at a rate
      of 0.5 mm every 12 hours for 30 days using a standard unilateral fixator system.
      Animals were euthanized 4, 8, or 12 weeks after the end of distraction. The
      lengthened tibia and the contralateral control tibia from each animal were
      evaluated by radiographic, densitometric (dual energy xray absorptiometry,
      quantitative computed tomography), and biomechanical (axial compression testing,
      torsion testing to failure) methods. The bone mineral density and maximum torque
      for the lengthened tibia were significantly greater in the 8-week group than in
      the 4-week group. However, the values in the 12-week group were significantly
      smaller than in the 8-week group. In the lengthened tibias, there was a
      correlation between the maximum torque and the bone mineral density, and between
      the maximum torque and the bone density. Bone density measurements are useful
      prognosticators for the safe removal of external fixators after leg lengthening
      procedures. By using these methods, clinical fractures after leg lengthening
      could be avoided in the future.

PMID- 9917723
TI  - A discrete soft tissue mass in the distal thigh of a 29-year-old man.

PMID- 9917725
TI  - ADA joins national coding and provider classification projects.

PMID- 9917724
TI  - Well-defined outcomes documentation needed.

PMID- 9917726
TI  - What they don't know could hurt them: increasing public awareness of folic acid
      and neural tube defects.

PMID- 9917727
TI  - Conflict of interest.

PMID- 9917728
TI  - Conflict of interest: an important issue in nutrition research and
      communications.

PMID- 9917729
TI  - Folate knowledge, intake from fortified grain products, and periconceptional
      supplementation patterns of a sample of low-income pregnant women according to
      the Health Belief Model.
AB  - OBJECTIVE: This study assessed folate-related knowledge and behaviors and folate
      intake from grain products, assuming 1998 fortification requirements, of
      socioeconomically disadvantaged pregnant women. DESIGN: Interviews (based on the
      Health Belief Model) concerning folate and neural tube defects were conducted in
      a prenatal care clinic. SUBJECTS/SETTING: The convenience sample of 251 low
      income, predominantly minority, pregnant women received services in an Atlanta,
      Georgia, public hospital. All subjects were eligible for or enrolled in the
      Special Supplemental Nutrition Program for Women, Infants, and Children.
      STATISTICAL ANALYSES: Frequency counts, means, and standard multiple linear
      regression. RESULTS: More than 80% of subjects did not take supplements
      preconceptionally. Many subjects (57%) had heard of folate, but fewer could
      correctly define folate (26%) or list any food sources of folate (30%). Most
      subjects (77%) will be able to achieve the goal of 400 micrograms folate per day
      exclusively through intake of fortified grain products. Approximately 20% of
      subjects will consume in excess of 1,000 micrograms folate per day solely through
      intake of fortified grains. Preconceptional use of supplements and several
      indicators of subjects' knowledge about folate were correlated with Health Belief
      Model constructs in manners consistent with the model framework.
      APPLICATIONS/CONCLUSIONS: This population of low-income women is likely to
      benefit substantially from folate fortification of grain products. However,
      health education remains essential for those women who are still unable to meet
      their folate requirements. The Health Belief Model may serve as an effective
      framework for tailoring folate educational interventions to high-risk
      populations. Research must be conducted into the risks of long-term high intakes
      of folate.

PMID- 9917730
TI  - Theory of Reasoned Action predicts milk consumption in women.
AB  - OBJECTIVE: To determine the factors influencing the consumption or avoidance of
      milk in women. SUBJECTS/SETTING: One hundred women completed food frequency
      questionnaires and a milk attitudes questionnaire framed within the Theory of
      Reasoned Action and performed sensory evaluations of different milk samples.
      STATISTICAL ANALYSES: Differences among milk types were assessed using 2-way
      analysis of variance and least-significant-difference mean comparison procedures.
      Correlation and multiple regression analyses, and standardized partial regression
      coefficients, were used to determine the contribution of each component of the
      model in predicting behavior. RESULTS: Mean age of the 100 subjects was 39 years
      (range = 20-70 years). Milk consumption among subjects was low; 23 subjects
      indicated that they seldom or never drank milk. Data from the dairy frequency
      questionnaire showed that the primary milk for 42%, 36%, 27%, and 18% of the milk
      drinkers was skim, 2%, 1%, and whole, respectively (subjects could indicate more
      than 1 type of milk consumed). The Theory of Reasoned Action indicated that
      health and familiarity belief items were most associated with attitudes toward
      milk consumption. Skim milk had significantly lower scores for taste and texture
      belief items than 1%, 2%, and whole milk (P < .05), yet more subjects reported
      that they drank skim milk (42%) than the other milk types. Sensory evaluation
      demonstrated that subjects linked whole milk significantly more than skim milk (P
      < .05). CONCLUSIONS/APPLICATIONS: Some people continue to consume skim milk for
      reasons other than beliefs about taste and texture or actual sensory preference.
      This study identifies important factors contributing to milk consumption such as
      beliefs, attitudes, and sensory evaluation, which can be used to develop a
      specific framework in which to examine other components of milk consumption
      behavior.

PMID- 9917731
TI  - Use of food nutrition labels is associated with lower fat intake.
AB  - OBJECTIVE: The Nutrition Labeling and Education Act of 1990 mandated that
      standardized nutrition information appear on almost all packaged foods
      manufactured after May 1994. This study describes the demographic and diet
      related psychosocial correlates of nutrition label use, and examines the
      relationship between label use and diet. DESIGN/SUBJECTS: Data are from a random
      digit-dial telephone survey of 1,450 adult residents of Washington State. The
      questionnaire assessed nutrition label use, fat-related diet habits, fruit and
      vegetable consumption, diet-related psychosocial factors, health behavior, and
      demographic characteristics. STATISTICAL ANALYSES: Analyses examined associations
      of demographic characteristics with nutrition label use; diet-related
      psychosocial factors and health behavior with nutrition label use, controlled for
      demographic characteristics; and nutrition label use with fat and fruit and
      vegetable intake, controlled for demographic characteristics and psychosocial
      factors. RESULTS: Nutrition label use was significantly higher among women,
      residents younger than 35 years, and residents with more than a high school
      education. When controlled for demographic characteristics, the strongest
      predictors of label use were believing in the importance of eating a low-fat
      diet, believing in an association between diet and cancer, and being in the
      maintenance stage of change for adopting a low-fat diet. Label use was
      significantly associated with lower fat intake and, after controlling for all
      demographic, psychosocial, and behavioral variables, explained 6% of the variance
      in fat intake (P < .001). Label use was not associated with fruit and vegetable
      consumption. APPLICATIONS/CONCLUSION: Persons successfully limiting their fat
      intake use nutrition labels, suggesting that the new nutrition labels are
      helpful. Dietetics professionals can use the results of this study to emphasize
      to their clients the importance of reading nutrition labels in maintaining a low
      fat diet.

PMID- 9917732
TI  - Asian students change their eating patterns after living in the United States.
AB  - OBJECTIVE: To collect information on changes in dietary patterns among Asian
      students before and after immigration to the United States. DESIGN: A
      questionnaire designed to collect information about background, changes in food
      habits, and frequency of food consumption from a 72-item food list was mailed to
      subjects. SUBJECTS/SETTING: Potential participants were students of local
      universities and junior colleges who were born in China, Taiwan, Hong Kong,
      Japan, or Korea and were aged 18 years or older. All subjects were required to
      have been residing in the United States for at least 3 months before the start of
      the study. Questionnaires were mailed to 120 potential participants. STATISTICAL
      ANALYSIS: Paired t tests were used to determine differences in eating patterns
      and frequency of food consumption of subjects before and after immigrating to the
      United States. RESULTS: Seventy-one questionnaires were returned. Because of
      missing information on 8 of these questionnaires, only 63 were used in the
      analysis, which gave a response rate of 53%. The number of students consuming
      only 2 meals per day increased significantly; 29 (46%) respondents skipped
      breakfast because of their school schedules. Despite no significant change in the
      frequency of snack consumption, a majority (n = 46; 73%) of the respondents were
      consuming more salty and sweet snack items. Subjects were eating out less often,
      but they were selecting more American-style fast foods when they did eat out.
      Significant increases were noted in consumption of fats/sweets, diary products,
      and fruits, and significant decreases were noted in the consumption of meat/meat
      alternatives and vegetables after immigration to the United States.
      APPLICATIONS/CONCLUSIONS: Results of this study could be useful to dietetics
      practitioners as they observe changes in dietary patterns of Asian immigrants.
      These health professionals can use this information to plan nutrition education
      programs for Asian groups so that they can make informed decisions in adapting to
      new eating patterns and make wise food choices in their new environment. It is
      important to help Asian immigrants retain healthful food habits from their
      original country and to encourage them to choose eating patterns of the new
      culture that are nutritionally sound.

PMID- 9917733
TI  - Body composition, dietary intake, and energy expenditure in nonobese, prepubertal
      children of obese and nonobese biological mothers.
AB  - OBJECTIVE: To determine differences in dietary intake, resting energy
      expenditure, activity level, fat-free mass, and percentage body and abdominal fat
      in nonobese children of obese mothers compared with nonobese children of nonobese
      mothers. DESIGN: Cross-sectional comparison study. Children's food diaries were
      analyzed to determine average energy and nutrient content. Resting energy
      expenditure of children was measured by means of indirect calorimetry. Children's
      activity levels were estimated through questionnaires administered during
      interviews. Dual-energy x-ray absorptiometry was used to estimate body
      composition of children. SUBJECTS: Mothers of subjects responded to
      advertisements and were recruited as nonobese (body mass index = 20 to 25) or
      obese (body mass index > or = 30). Offspring included in the study were
      prepubertal and nonobese (10th to 90th percentile of weight for height by
      gender). Twelve pairs of children could be matched for weight, gender, and age.
      STATISTICAL ANALYSIS PERFORMED: Wilcoxon signed rank tests were used to determine
      differences between the 2 groups of children. RESULTS: Percentage abdominal fat
      was greater (median difference = 3.15, P = .001) and fat-free mass was lower
      (median difference = 1.19, P = .04) in children of obese mothers compared with
      children of nonobese mothers. No statistically significant differences between
      the 2 groups of children were found for dietary intake, resting energy
      expenditure, activity level, or percentage body fat. APPLICATIONS/CONCLUSIONS:
      The significantly higher percentage of abdominal fat and lower fat-free mass in
      children of obese mothers may contribute to obesity onset. Use of dual-energy x
      ray absorptiometry as a screening tool for nonobese, prepubertal children with an
      obese parent will help to identify those at risk. Education and lifestyle changes
      can then be implemented to help prevent the onset of obesity.

PMID- 9917734
TI  - Participants' evaluation of a weight-loss program.
AB  - OBJECTIVE: The purpose of this study was to evaluate participants' perceptions of
      the weight-loss intervention used in a hypertension prevention clinical trial.
      DESIGN: A total of 308 overweight and moderately obese subjects participated in
      the weight-management intervention. After the 18-month program, 281 participants
      completed a questionnaire designed to evaluate their perceptions of the program's
      effectiveness. SUBJECTS/SETTING: Adult participants (224 men and 84 women) in the
      weight-loss modality of the Trials of Hypertension Prevention Phase I, surveyed
      in 1991. STATISTICAL ANALYSES PERFORMED: chi 2 Analyses were used to test for
      statistical significance of group differences. RESULTS: Intervention components
      that were most useful are presented. Older participants (older than 50 years)
      were most likely to attend sessions and women were most likely to identify stress
      and frustration because of disappointing results. Successful participants were
      more likely to incorporate exercise into their daily activities, exercise
      regularly, and use self-monitoring strategies. Few participants found group
      exercise to be useful. CONCLUSION: These findings suggest that interventionists
      in weight-loss programs need to find flexible and creative ways to maintain
      contact with participants, continue to develop better methods of self-monitoring,
      obtain the skills needed to recognize frustration and provide timely support,
      continue to couple the message of diet and exercise, and emphasize helping
      participants develop their problem-solving skills. This may require training
      outside the traditional field of dietetics.

PMID- 9917735
TI  - How to make nutrition education more meaningful through facilitated group
      discussions.
AB  - Facilitated group discussions provide an alternative method to lecture and one-on
      one approaches for conducting educational interventions at clinic sites. They are
      an interactive form of education wherein learners generate the specific topics to
      be addressed and share their knowledge and experience with other group members
      through discussion. In brief, the educator becomes a facilitator who, rather than
      lecturing, encourages clients to discuss freely among themselves their own
      approach to the nutrition problems posed during the session. As a facilitator,
      the nutritionist strives to create a comfortable atmosphere for discussion,
      encourages participation, and interjects only to correct misinformation and
      manage group dynamics. Facilitated group discussions allow nutrition
      practitioners to deliver meaningful nutrition education in a manner that helps
      empower their clients to improve their dietary habits; at the same time such
      discussions meet the increased public administrative demands for efficiency.
      Possible benefits to clients include more confidence, better communication
      skills, improved thinking skills, and increased motivation and commitment to
      improving nutrition behavior. We recommend that nutrition educators try
      facilitated group discussions in their clinics.

PMID- 9917736
TI  - Authorship: can you claim a byline?
AB  - Decisions about bylines, although seemingly straightforward, can "breed ill
      will," "wreck friendships," and "even damage careers" if decisions are not in
      accord with professional guidelines and common sense. Editors have attempted to
      promote responsible authorship by creating Uniform Requirements. According to the
      International Committee of Medical Journal Editors, each author must have made a
      substantial contribution to all 3 of the following conditions to qualify for
      authorship: conceiving and designing the work represented by the article or
      analyzing and interpreting data; drafting the article or revising it critically
      for important intellectual content; and giving final approval of the version to
      be published. Despite these guidelines, bylines continue to include grafters and
      guests. Researchers believe guidelines for authorship are necessary but suggest
      the existing Uniform Requirements may be overly restrictive and easily
      misinterpreted. Editors will need to work with researchers to reach consensus on
      realistic and appropriate guidelines for authorship.

PMID- 9917737
TI  - Knowledge of folic acid and neural tube defects among inner-city residents: have
      they heard about it?

PMID- 9917738
TI  - Attendance at breast-feeding support meetings: relationship to demographic
      characteristics and duration of lactation in women planning postpartum
      employment.

PMID- 9917739
TI  - Attitudes toward breast-feeding among WIC employees in San Diego County.

PMID- 9917740
TI  - Cultural influences on infant feeding beliefs of mothers.

PMID- 9917741
TI  - Knowing brand name affects patient preferences for enteral supplements.

PMID- 9917742
TI  - Position of the American Dietetic Association: dietary guidance for healthy
      children aged 2 to 11 years.

PMID- 9917743
TI  - Report on the 1997 Membership Database of the American Dietetic Association.

PMID- 9917744
TI  - Code of Ethics for the profession of dietetics. The American Dietetic
      Association.

PMID- 9917745
TI  - Total body irradiation, cyclophosphamide, and etoposide with stem cell transplant
      as treatment for infants with acute lymphocytic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) in infants has a very poor outcome
      with modern chemotherapy. We reviewed our experience with the infants diagnosed
      with ALL at Children's Memorial Hospital from 1992 to 1997. PROCEDURE: During
      this time period, 10 infants were diagnosed with ALL. Seven of them were
      transplanted, four with marrow from HLA-matched siblings and three with umbilical
      cord blood. Four of the transplanted patients had the MLL gene rearrangement and
      the other three transplanted patients had one or more other high-risk features
      including CD10-blasts, age less than 6 months at diagnosis, or prior relapse. The
      patients were conditioned with a regimen of total body irradiation (TBI),
      etoposide, and cyclophosphamide (CY). Peritransplant toxicity was tolerable. The
      graft infused contained a median total nucleated cell dose/kg of 3 x 10(8) (.3 x
      10(8)-6 x 10(8)). The median CD34+ cell dose/kg was 5 x 10(6) (.25 x 10(6)-31 x
      10(6)). RESULTS: All of the patients engrafted with a median of 18 days (11-29)
      to reach an absolute neutrophil count (ANC) of 500/microliter. The median time to
      reach an unsupported platelet count greater than 20,000/microliter was 24 days
      (18-64). Four of seven of the transplanted patients are leukemia-free survivors
      at a median follow-up of 775 days. Of the three patients who were not
      transplanted, one is surviving 2+ years off therapy. CONCLUSIONS: Allogeneic stem
      cell transplant is an alternative to chemotherapy alone as a treatment for infant
      ALL when a suitable donor is available.

PMID- 9917746
TI  - Large-volume leukapheresis procedure for peripheral blood progenitor cell
      collection in children weighing 15 kg or less: efficacy and safety evaluation.
AB  - BACKGROUND: We update our experience on large-volume leukapheresis (LVL) in very
      small patients with malignancies. LVLs were performed with the aim of reducing
      the psychological impact of leukaphereses by reducing the number of procedures
      while collecting large numbers of cells. PROCEDURE: Seventeen LVLs were performed
      using a Cobe Spectra separator in 14 patients weighing < or = 15 kg. A median of
      3.8 patient's blood volumes corresponding to 296 mL/kg (range, 202-565) of blood
      was processed per session of 190 minutes (120-279) duration. A femoral catheter
      was installed specially for collection for 88% LVL (vs. 35% for standard
      leukaphereses). A median volume of 16.9 mL/kg was collected with 5.4 x 10(8)
      MNC/kg (range, 0.6-16.3) and 8.2 x 10(6) CD34+ cells/kg (range, 1.3-31.7).
      RESULTS: No signs of complications due to citrate toxicity were encountered. No
      hypotensive or hypothermic episodes were observed. Platelet counts were
      significantly diminished after each procedure (median: -59%). When the
      extracorporal line was not primed with red blood cells (RBC), the difference
      between pre-LVL and post-LVL hemoglobin levels was significant with a median 32
      g/L decrease. CONCLUSIONS: The LVL approach for peripheral blood progenitor cells
      (PBPC) collection in very small children may expose them to the risk of anemia
      and thrombocytopenia and an excess of special central line installation. The
      application of this technique in these patients should be reserved for special
      cases when a very large number of cells must be collected and should be performed
      by an experienced team.

PMID- 9917747
TI  - Osteonecrosis during the treatment of childhood acute lymphoblastic leukemia: a
      prospective MRI study.
AB  - BACKGROUND: Since the survival rates of childhood leukemia have improved,
      attention is increasingly focused on the long-term effects of the treatment.
      Osteonecrosis may complicate the treatment of acute lymphoblastic leukemia (ALL).
      To have more information about the natural history and clinical course of the
      development of osteonecrosis, a prospective MRI study was designed. PROCEDURE:
      The development of osteonecrosis was studied prospectively in 24 consecutive
      children with ALL who underwent T1-weighted magnetic resonance imaging (MRI)
      scanning of the lower extremities at the beginning of, during, and at the
      cessation of the chemotherapy. The general bone marrow signal intensity was
      assessed together with focal lesions. Circumscribed lesions with a rim of low
      signal intensity were considered typical of osteonecrosis. RESULTS: Nine of the
      24 patients (rate 38%) developed osteonecrosis during the treatment. Six of them
      were asymptomatic. MRI lesions regressed in size in six patients, and in three
      patients the MRI finding returned to normal. No operative treatment was needed.
      The osteonecroses appeared immediately or within a few months after the delayed
      intensification phase with intensive dexamethasone medication. CONCLUSIONS:
      Corticosteroids have been considered to be the main pathogenetic factor in the
      development of osteonecrosis in children with malignancies, which was also
      suggested by our findings. However, there is a lack of systematic prospective
      studies concerning the natural history and long-term follow-up observations of
      the prognosis of osteonecrosis, especially in pediatric patients. Based on our
      results, the lesions are often asymptomatic and cause no disability, and
      spontaneous improvement or even resolution may occur.

PMID- 9917748
TI  - Hodgkin disease in children: clinicoepidemiologic and viral (Epstein-Barr virus)
      analyses.

PMID- 9917749
TI  - Successful extracorporeal membrane oxygenation in four children with malignant
      disease and severe Pneumocystis carinii pneumonia.
AB  - BACKGROUND: Toxic deaths due to intensified treatment are of increasing concern
      in view of the generally improved prognosis for children with malignancies.
      Pneumocystis carinii pneumonia (PCP) during immunosuppressive treatment in
      children with malignancies is a severe complication with a poor prognosis if
      mechanical ventilation is required. Extracorporeal membrane oxygenation (ECMO) is
      a recognized technique that provides temporary respiratory support for patients
      with intractable respiratory failure. PROCEDURE: We here report successful ECMO
      support in four children with PCP, secondary to chemotherapy-induced
      immunosuppression, in whom the respiratory situation deteriorated despite
      pharmacological treatment and mechanical ventilation. The duration of ECMO was 7
      43 days. RESULTS: Three children with acute lymphoblastic leukemia recovered from
      their PCP to continue chemotherapy and are now in complete continuous remission.
      Their pulmonary function normalized completely during 6-12 months after ECMO
      therapy. One child with a primitive neuroectodermal tumor survived the PCP and
      was off ECMO for 11 days before succumbing to unrelated complications.
      CONCLUSIONS: We conclude that ECMO offers an important means of respiratory
      support in children with severe PCP that can also be adopted during treatment for
      malignant disease.

PMID- 9917750
TI  - Synovial sarcoma: report of a series of 25 consecutive children from a single
      institution.
AB  - BACKGROUND: The role of postoperative radiotherapy and adjuvant chemotherapy in
      the treatment of synovial sarcoma remains to be determined. PROCEDURE: Twenty
      five children were treated during a 23-year period with a multimodality approach.
      All of them had resection of the primary tumor (three amputations), followed by
      surgical retreatment in eight. Postoperative radiotherapy was delivered to 16
      patients and adjuvant chemotherapy was given to 22. RESULTS: At the time of the
      report, 19 patients were alive and without evidence of disease. Six developed
      distant metastases (one associated with local recurrence); five of them died of
      their disease and one was alive in complete remission at 4 years from relapse.
      With a median follow-up of 9 years (range 2-23), the survival and the event-free
      survival at 5 years were 80% (SE 8.2) and 74% (SE 9.2), respectively. All
      relapsing patients had been classified as T2B. CONCLUSIONS: Multimodality
      treatment yielded satisfying survival results using limb-preserving surgery in
      most cases. Tumor size > 5 cm and invasiveness, which defined stage T2B, were the
      most important predictors of poor outcome. Evaluation of the role of adjuvant
      chemotherapy and radiotherapy awaits prospective studies, even if T2B patients,
      as well as children having nonradical surgery, seem worth managing by adjuvant
      treatments.

PMID- 9917751
TI  - Hemihypertrophy and a poorly differentiated embryonal rhabdomyosarcoma of the
      pelvis.
AB  - BACKGROUND: Asymmetry of the limbs (conventionally known as hemihypertrophy) is
      one of the overgrowth syndromes occurring sporadically in the general population
      at a frequency of approximately 1:86,000. Hemihypertrophy is also reported as
      part of the Beckwith-Wiedemann syndrome which has as its cardinal features
      omphalocele, macroglossia and gigantism with hypoglycemia, organomegaly, renal
      anomalies, hemihypertrophy, and embryonal tumors occurring less frequently.
      Various neoplasms are also associated with isolated hemihypertrophy. Wilms tumor,
      adrenocortical carcinoma, and hepatoblastoma are the most frequent.
      Rhabdomyosarcoma, neuroblastoma, phaeochromocytoma, and undifferentiated sarcoma
      of the lung are encountered only rarely. Loss of heterozygosity (LOH) of
      chromosome 11p15.5 is strongly associated with childhood embryonal tumors,
      particularly Wilms tumor, hepatoblastoma, and rhabdomyosarcoma. PROCEDURE AND
      RESULTS: In this article, we describe an adolescent male with congenital
      asymmetry of the lower limbs who presented with a large poorly differentiated
      pelvic sarcoma. Conventional histologic, immunohistochemical, and ultrastructural
      studies of this tumor were insufficient for accurate subclassfication. However,
      positive staining for MyoD1 (a recently identified embryonically expressed marker
      of muscle differentiation) and LOH at the tyrosine hydroxylase locus of
      chromosome 11p15.5 by molecular analysis favored the diagnosis of embryonal
      rhabdomyosarcoma over an undifferentiated sarcoma. CONCLUSIONS: This case
      stresses the importance of pursuing clinical findings when they occur in
      conditions with an increased risk of developing cancer, which in this case was
      asymmetry of a limb. Also illustrated by this patient is the need for early
      consideration of molecular diagnostic tests where available, to refine an
      uncertain pathologic diagnosis that may ultimately have an impact on treatment
      and prognosis.

PMID- 9917752
TI  - Guidelines for assistance to terminally ill children with cancer: a report of the
      SIOP Working Committee on psychosocial issues in pediatric oncology.
AB  - This, the sixth official document of the SIOP Working Committee on psychosocial
      issues in pediatric oncology, develops another important and especially difficult
      topic: assistance for terminally ill children with cancer. This is provided for
      the pediatric oncology community as a useful set of guidelines. It should be
      always possible for a declining child to die without unnecessary physical pain,
      fear, or anxiety. It is essential that he or she receive adequate medical,
      spiritual, and psychological support, and that the child at no point feels
      abandoned. Palliative care, in the terminal phase of cancer, should be tailored
      to the different needs and desires of the child and the family, with the goal of
      providing the best possible quality of life for the days that remain.

PMID- 9917753
TI  - Childhood cancer etiology: recent reports.

PMID- 9917754
TI  - Pleuropulmonary blastoma.

PMID- 9917755
TI  - Vertebra plana due to a Ewing tumor.

PMID- 9917756
TI  - Screening asymptomatic, middle-aged men for carcinoma of the prostate: can we all
      stop shouting out our answer for a minute and think about the question?

PMID- 9917757
TI  - Screening for carcinoma of the prostate.

PMID- 9917758
TI  - Epidemiologic studies of childhood leukemia: where do we go from here?
AB  - Much of our knowledge of the mechanisms of carcinogenesis has resulted from the
      study of rare cancers, including retinoblastoma, angiosarcoma, and vaginal clear
      cell carcinoma. Due to the heterogeneity of childhood leukemia, epidemiologic
      studies that focus on children with unique clinical and genetic manifestations of
      the disease could potentially lead to further understanding of leukemogenesis.

PMID- 9917759
TI  - Systemizing childhood cancer care in Hungary: twenty-five years of progress.
AB  - Steady and significant progress has been made in the organization of Hungarian
      pediatric oncology. This has been done through the mobilization of social,
      scientific, medical, and economic resources of Hungary, a small nation. The
      lessons learned, and the measures adopted, may prove useful to other countries
      facing similar limitations and problems.

PMID- 9917760
TI  - Applicability of the Hungarian experience to PODC.

PMID- 9917761
TI  - Leukemic infiltrations of the peritoneum at diagnosis and the breast at relapse
      in a child with acute B-cell lymphoblastic leukemia.

PMID- 9917762
TI  - Prader-Willi syndrome and intratubular germ cell neoplasia.

PMID- 9917763
TI  - Multiple chest wall masses presenting in nasopharyngeal carcinoma.

PMID- 9917764
TI  - Contamination of poliovirus vaccine with SV40 and the incidence of
      medulloblastoma.

PMID- 9917765
TI  - Cat-scratch disease.

PMID- 9917766
TI  - Management of B. henselae neuroretinitis in cat-scratch disease.

PMID- 9917767
TI  - Retinal breaks.

PMID- 9917768
TI  - Cyclosporine and neovascularization.

PMID- 9917769
TI  - Pupil dilation using phenylephrine alone or in combination with tropicamide.

PMID- 9917770
TI  - LASIK in different degrees of myopia.

PMID- 9917771
TI  - Estimation of cataract blindness in India.

PMID- 9917772
TI  - Ocular dominance in baseball players.

PMID- 9917773
TI  - Color coding medications.

PMID- 9917774
TI  - Acknowledging the importance of study design in the organization and quality of
      manuscripts.

PMID- 9917775
TI  - Complications of laser in situ keratomileusis for the correction of myopia.
AB  - OBJECTIVE: To determine the incidence and severity of complications from laser in
      situ keratomileusis (LASIK) for the correction of myopia by experienced and
      inexperienced surgeons. DESIGN: Prospective, observational clinical study.
      PARTICIPANTS: Fourteen surgeons and 1062 eyes of 574 myopic patients who desired
      surgical correction of myopia ranging from -2.00 to -22.50 diopters (D; mean, 
      7.57 D) and astigmatism no greater than 4.00 D participated in this study.
      INTERVENTION: Myopia was corrected with LASIK. Astigmatism was corrected with
      arcuate keratotomy at the same time as the initial procedure or subsequently.
      MAIN OUTCOME MEASURES: Primary outcome measures were change in best spectacle
      corrected visual acuity (BSCVA) and the incidence of complications. RESULTS: Eyes
      were followed for a mean of 9.5 months after their last surgical procedure
      (range, 2 weeks-21 months). Three hundred eighty-one eyes (36%) underwent 468
      enhancement procedures 3 months or more after the initial treatment. There were
      27 (2.1%) intraoperative and 40 (3.1%) postoperative complications. Laser
      ablation was not performed during the initial treatment of 17 (1.6%) eyes because
      of intraoperative complications. Seventy-four eyes gained 2 or more lines of
      BSCVA, while 50 eyes lost 2 or more lines of BSCVA. Only three eyes lost two or
      more lines of BSCVA to a level worse than 20/40. One eye with a flap buttonhole
      (BSCVA 20/50) also had an epiretinal membrane. The second eye (BSCVA 20/60) had a
      flap buttonhole that may have been related to a previous corneal transplant. The
      third eye (-22.50 D before surgery) had a rhegmatogenous retinal detachment
      develop, reducing BSCVA from 20/60 to 20/200. The incidence of intraoperative
      complications decreased from 3.1% during the first 3 months to 0.7% during the
      last 9 months of the study (P = 0.02). CONCLUSIONS: LASIK is acceptably safe for
      the correction of myopia. Although complications occur in approximately 5% of
      cases, these rarely lead to visual loss of more than two Snellen lines and
      postoperative acuity below 20/40. Flap buttonholes were more likely to cause loss
      of BSCVA than free or incomplete flaps (P = 0.02); flap buttonholes may be more
      likely in eyes that have undergone previous surgery. Complication rates can be
      reduced as the surgical team gains experience.

PMID- 9917776
TI  - Retreatment after laser in situ keratomileusis.
AB  - OBJECTIVE: To evaluate the effectiveness, predictability, and safety of laser in
      situ keratomileusis (LASIK) retreatment for correcting residual myopia. DESIGN:
      Retrospective noncomparative case series. PARTICIPANTS AND INTERVENTION: Fifty
      nine consecutive eyes (43 patients) underwent LASIK retreatment at 3 or 6 months
      after the primary LASIK procedure. Lifting the corneal flap and reablating the
      stromal bed with a VISX 20/20 excimer laser was the procedure used for LASIK
      enhancement. MAIN OUTCOME MEASURES: The following parameters were studied before
      and after retreatment: visual acuity, refraction, videokeratography, applanation
      tonometry, and corneal thickness. Complications after LASIK enhancement also were
      evaluated. Follow-up was 12 months. RESULTS: Before retreatment, only 3.38% of
      eyes (2 of 59) had an uncorrected visual acuity of 0.5 (20/40) or better, and
      after retreatment, this percentage increased to 60% (30 of 50) at 6 months and
      61.8% (34 of 55) at 12 months. After reoperation, mean best-corrected visual
      acuity improved by half a line over the values before retreatment. The
      preretreatment refraction of -2.92 +/- 1.22 diopters (D) (mean +/- standard
      deviation) decreased significantly to -0.44 +/- 0.80 D at 6 months and to -0.61
      +/- 0.82 D at 12 months (P < 0.001). In 82% of eyes (41 of 50) at 6 months and
      81.8% (45 of 55) at 12 months, the spherical equivalent was within 1.00 D of
      emmetropia. There was a significant regression of effect (0.38 D) between 3 and
      12 months (P < 0.01). Postretreatment refraction was related to the original
      refraction before the primary LASIK, the preretreatment refraction, and the
      ablation diameter used. Although no vision-threatening complications were found,
      epithelial ingrowth and flap melting were more common after than before LASIK
      retreatment, with 31% of eyes at 12 months with epithelial ingrowth and 10.9%
      with flap melting. However, LASIK enhancement improved decentration and night
      vision problems. CONCLUSIONS: LASIK retreatment was an effective and predictable
      procedure for correcting residual myopia. Epithelial ingrowth and flap melting
      were more frequent after than before LASIK retreatment, whereas decentration and
      night-vision symptoms improved.

PMID- 9917777
TI  - Epithelial removal with the excimer laser (laser-scrape) in photorefractive
      keratectomy retreatment.
AB  - OBJECTIVES: To retrospectively evaluate refractive and topographic outcomes after
      excimer laser photorefractive keratectomy (PRK) retreatment using the laser
      scrape technique for epithelial removal. DESIGN: Retrospective clinical study.
      PARTICIPANTS: Thirty eyes of patients who had PRK retreatment for undercorrection
      after primary PRK were examined. INTERVENTION: The PRK retreatment was performed
      using a laser-scrape technique in which the excimer laser was used to remove the
      majority of the epithelium overlying the anterior stromal surface before
      additional PRK ablation. MAIN OUTCOME MEASURES: Uncorrected visual acuity, best
      corrected visual acuity (BCVA), surface regularity index (SRI), and surface
      asymmetry index were measured. RESULTS: Primary PRK was performed for myopia of 
      5.1 +/- 1.7 diopters (range, -1.1 to -7.5 diopters). Mean spherical equivalent
      (SE) was -1.3 +/- 0.4 diopters (range, -0.6 to -2.0 diopters) before retreatment.
      Mean SE 6 months after retreatment decreased to +0.1 +/- 0.4 diopter (range,
      +1.25 to -0.75 diopters; P < 0.0001). Four eyes (15%) were more than +0.5 diopter
      overcorrected at 6 months. Ninety-six percent of eyes achieved mean SE within +/-
      1 diopter and 77% within +/- 0.5 diopter of emmetropia after retreatment. Visual
      acuity improved significantly 6 months after reablation (P < 0.0001) with 100%
      20/40 or better and 73% 20/25 or better without correction. Final BCVA also
      improved compared with before retreatment (P = 0.02). Twelve eyes gained 1 line
      of BCVA and no eye lost more than 1 line of BCVA. The SRI before retreatment was
      0.6 +/- 0.3 (range, 0.0-0.9) and remained the same 0.6 +/- 0.2 (range, 0.1-1.0; P
      = 0.8), 6 months after retreatment. CONCLUSION: Excimer laser PRK retreatment
      using the laser-scrape technique for epithelial removal is an accurate and safe
      procedure for treating undercorrection of eyes after PRK for low-to-moderate
      myopia.

PMID- 9917778
TI  - Diabetes, hypertension, and central obesity as cataract risk factors in a black
      population. The Barbados Eye Study.
AB  - OBJECTIVE: The increased cataract prevalence of black populations, especially of
      cortical cataract, remains unexplained. The authors evaluate the relationships of
      diabetes, hypertension, and obesity patterns to lens opacities, by age, among
      4314 black participants in the Barbados Eye Study. DESIGN AND PARTICIPANTS:
      Prevalence study of a random sample of the Barbados population, ages 40 to 84
      years (84% participation). MAIN OUTCOME MEASURES: Associations with age-related
      lens changes (grade > or = 2 in the Lens Opacities Classification System II at
      the slit lamp) were evaluated in logistic regression analyses by age (persons <
      60 years and > or = 60 years). Results are presented as odds ratios (OR) with 95%
      confidence intervals. RESULTS: Of the 1800 participants with lens changes, most
      had cortical opacities. Diabetes history (18% prevalence) was related to all lens
      changes, especially at younger ages (age < 60 years: OR = 2.23 [1.63, 3.04]; age
      > or = 60 years: OR = 1.63 [1.22, 2.17]). Diabetes also increased the risk of
      cortical opacities (age < 60 years: OR = 2.30 [1.63, 3.24]; age > or = 60 years:
      OR = 1.42 [1.03, 1.96]); additional risk factors were high diastolic blood
      pressure (age < 60 years: OR = 1.49 [1.00, 2.23]) and higher waist/hip ratio (all
      ages: OR = 1.36 [1.00, 1.84]). Diabetes was also related to posterior subcapsular
      opacities. Glycated hemoglobin levels were positively associated with cortical
      and posterior subcapsular opacities. Overall, 14% of the prevalence of lens
      changes could be attributed to diabetes. CONCLUSIONS: The high prevalence of
      cortical opacities was related to diabetes, hypertension, and abdominal obesity,
      which also are common in this and other black populations. Interventions to
      modify these risk factors, especially in populations in which they are highly
      prevalent, may have implications to control visual loss from cataract, which is
      the first cause of blindness worldwide.

PMID- 9917779
TI  - Intraoperative clinical practice and risk of early complications after cataract
      extraction in the United States, Canada, Denmark, and Spain.
AB  - OBJECTIVE: To examine variation in intraoperative clinical practice and rates of
      adverse events after cataract surgery across four different healthcare systems.
      DESIGN: Multicenter cohort study. PARTICIPANTS: Patients were recruited from
      ophthalmic clinics in the United States (n = 75); in the Province of Manitoba,
      Canada (n = 12); in Denmark (n = 17); and the City of Barcelona, Spain (n = 10).
      In all, 1420 patients undergoing first eye cataract surgery were enrolled, with
      preoperative, perioperative, and postoperative clinical data collected on 1344
      patients (95%). MAIN OUTCOME MEASURES: Occurrence of 23 specified intraoperative
      and early postoperative adverse events was measured. Four-month postoperative
      visual acuity outcome also was measured. RESULTS: Phacoemulsification was
      performed in two thirds of the extractions in the United States and Manitoba, in
      one third in Denmark, and in 3% in Barcelona (P < 0.001). More than 96% of
      extractions in North America and Denmark were performed with the patient under
      local anesthesia, whereas general anesthesia was used for 38% of extractions in
      Barcelona (P < 0.001). Rates of intraoperative adverse events were 11% to 12.8%
      in Manitoba, Denmark, and Barcelona and significantly lower in the United States
      (6%), mainly because of a lower rate of capsular rupture (P < 0.01).
      Significantly higher rates of early postoperative events were seen in the United
      States (18.8%) and Manitoba (20.4%) compared to Denmark (7.9%) and Barcelona (5%)
      (P < 0.001). The differences among sites in rates of events could not be
      explained by differences in recorded patient characteristics or surgical
      techniques. The occurrence of perioperative events was significantly associated
      with a worse 4-month visual outcome. CONCLUSION: The observed variation in
      clinical practice might represent a general trend of a slower diffusion of new
      medical technology in Europe compared with that of North America. Rates of
      intraoperative and early postoperative events varied significantly across sites.

PMID- 9917780
TI  - The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular
      lenses on posterior capsular opacification 3 years after cataract surgery.
AB  - OBJECTIVE: To compare the visual outcome, neodymium:YAG (Nd:YAG) capsulotomy
      rates, and percentage of posterior capsular opacification (PCO) seen with
      polymethylmethacrylate (PMMA), silicone, and polyacrylic intraocular lens
      implants 3 years after surgery. DESIGN: Randomized, prospective trial.
      PARTICIPANTS: Ninety eyes of 81 patients were examined at a British teaching
      hospital. INTERVENTION: Ninety eyes were prospectively randomized to receive a
      PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort Worth, TX) implant. All
      lenses had 6-mm disc optics with PMMA haptics. A standardized surgical protocol
      was performed by a single surgeon using an extracapsular technique with
      capsulorhexis; any surgical complications were excluded and all patients had
      standardized postoperative medication and follow-up. MAIN OUTCOME MEASURES:
      Patients were seen at 6 months and 1, 2, and 3 years after surgery. At 3 years,
      logarithm of the minimum angle of resolution (LogMAR) visual acuity and Pelli
      Robson contrast sensitivity were measured and YAG capsulotomy rates determined.
      Posterior capsular opacification was assessed objectively by digital
      retroillumination imaging using dedicated software and calculated as the
      percentage area of opacified capsule. RESULTS: At 3 years, the overall follow-up
      rate was 71%: 19 patients were available for examination with polyacrylic lens
      implants, 22 with silicone, and 23 with PMMA. There was a significant difference
      in percentage PCO at 3 years among the lens types (P = 0.0001). Polyacrylic
      lenses were associated with less PCO (10%) than silicone (40%) and PMMA lenses
      (56%). The YAG capsulotomy rate was 0% for polyacrylic, 14% for silicone, and 26%
      for PMMA (P = 0.05). The visual acuity and contrast sensitivity were not
      significantly different among the three groups if patients with age-related
      macular degeneration and those requiring YAG capsulotomies are excluded.
      CONCLUSIONS: Intraocular lenses made from polyacrylic are associated with a
      significantly reduced degree of PCO and lower YAG rates.

PMID- 9917781
TI  - Piggybacking intraocular implants to correct pseudophakic refractive error.
AB  - OBJECTIVE: To determine the safety and efficacy of implanting a second
      intraocular lens (IOL) to correct pseudophakic refractive error. DESIGN:
      Noncomparative, prospective, consecutive case series. PARTICIPANTS: Eight eyes of
      eight normal pseudophakes and seven eyes of seven postpenetrating keratoplasty
      (PK) pseudophakes were included in the study. INTERVENTION: A second intraocular
      lens (IOL) was implanted anterior to the first in each eye in the study. MAIN
      OUTCOME MEASURES: Efficacy was determined based on the achieved refractive
      correction and Snellen uncorrected visual acuity measurements. Safety was
      determined based on loss of best-corrected visual acuity and operative and
      postoperative complications. RESULTS: Before surgery, spherical equivalents
      ranged from -5.12 diopters (D) to 7.5 D, with a mean absolute deviation from
      emmetropia of 3.38 D (1.62). After surgery, spherical equivalents ranged from 
      2.75 D to 0.5 D, with a mean absolute deviation from emmetropia of 1.21 D (0.90).
      Before surgery, only 7% of patients had 20/40 or better uncorrected vision,
      whereas after surgery, 50% had that level of vision. CONCLUSIONS: Implanting a
      second IOL is a viable option for correcting pseudophakic refractive error.

PMID- 9917782
TI  - A comparison of patient comfort during cataract surgery with topical anesthesia
      versus topical anesthesia and intracameral lidocaine.
AB  - OBJECTIVE: To determine whether intraocular lidocaine increases patient comfort
      during cataract surgery while under topical anesthesia. DESIGN: Prospective,
      randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: Both
      men and women between 45 and 85 years of age who were scheduled for elective
      cataract surgery while under topical anesthesia participated. Sixty-eight
      patients were randomized to each group. INTERVENTION: Patients were randomized to
      receive either topical anesthesia plus intracameral 1% preservative-free
      lidocaine or intracameral balanced salt solution. MAIN OUTCOME MEASURES: Patient
      assessment of pain during delivery of the anesthesia, surgery, and after surgery
      using a visual analog pain scale was measured. Patients also recorded the degree
      to which they were bothered by tissue manipulation and the microscope light.
      Surgeon assessments of operative conditions, patient cooperation, and
      intraoperative complications were recorded. The attending anesthesiologist
      recorded any required supplemental intravenous sedation and any increase in pulse
      or increase in blood pressure. RESULTS: There was no significant difference in
      patient-reported pain scores for delivery of anesthesia (P = 0.902), surgery (P =
      0.170), or after surgery (P = 0.680). Patients in the lidocaine group reported
      being less bothered by tissue manipulation (P = 0.021). The surgeon assessment
      showed more patient cooperation in the lidocaine group (P = 0.043). CONCLUSIONS:
      Both topical anesthesia alone and topical anesthesia plus intracameral lidocaine
      provide good operative conditions for the surgeon and comfortable surgical
      circumstances for the patient. Injection of intraocular lidocaine increases
      patient cooperation and decreases the degree to which patients are bothered by
      tissue manipulation, two outcomes that justify its use.

PMID- 9917783
TI  - Conjunctival rotation autograft for pterygium. An alternative to conjunctival
      autografting.
AB  - OBJECTIVE: To determine the safety and efficacy of conjunctival rotation
      autografting (CRA) as an alternative to conventional conjunctival autograft after
      pterygium excision. DESIGN: Prospective noncomparative case series. PARTICIPANTS:
      Consecutive patients seen at the Pterygium Clinic of the Singapore National Eye
      Centre who were thought to be unsuitable for conventional conjunctival
      autografting underwent a modified surgical procedure, which the authors describe
      as CRA. There were 51 rotation autografts performed on 45 eyes of 43 patients.
      INTERVENTION: In this procedure, the underlying fibrovascular pterygium tissue
      was removed and the original epithelium (with minimal subepithelial tissue
      included) replaced over the bare sclera with a 180 degrees rotation. Surgeries
      were performed by one surgeon (DT) from April 1995 to May 1996. MAIN OUTCOME
      MEASURE: Pterygium recurrence and complications of CRA were measured. RESULTS:
      The mean follow-up time was 12 months (range, 2-22 months). There were 46 primary
      and 5 recurrent pterygia. The indications for CRA were combined cataract and
      pterygium surgery (39.2%), double pterygia (31.4%), the need to preserve the
      superior conjunctiva (21.6%), and superior conjunctival scarring (7.8%). There
      were two recurrences (4% recurrence rate), one occurring at 4 months and the
      other occurring at 7 months after surgery. No significant complications were
      encountered. However, 50% of the grafts remained mildly injected for more than 3
      months, and some remained injected for up to 13 months after surgery (average of
      4 months). Pigmentary changes were also noted in six grafts (12%). CONCLUSION:
      Conjunctival rotation autografting is a useful technique of conjunctival grafting
      in cases in which it is not possible or desirable to use the superior conjunctiva
      as a donor source.

PMID- 9917784
TI  - Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid.
AB  - PURPOSE: The authors performed a prospective evaluation of the efficacy of
      treating ocular cicatricial pemphigoid (OCP) with subconjunctival mitomycin C.
      DESIGN: Unmasked, prospective, internally controlled case series. METHODS:
      Patients were eligible for treatment with subconjunctival mitomycin C under three
      criteria: (1) significant complications of systemic immunosuppressant therapy;
      (2) markedly asymmetric conjunctival disease; and (3) end-stage OCP. All patients
      received monocular subconjunctival injections of 0.25 ml of 0.2 mg/ml mitomycin C
      to both the superior and inferior bulbar conjunctivae in the eye with the more
      severe disease. RESULTS: Nine eyes of nine patients (mean age, 74 years) were
      treated with subconjunctival mitomycin C to the more-involved eye and were
      followed for a mean of 23.5 months (range, 12-40 months). Eight of nine patients
      showed quiescence of their OCP in the treated eye based on serial evaluation of
      conjunctival cicatrization and grading of conjunctival erythema. Five of the nine
      untreated eyes showed progression of the conjunctival disease. One patient
      required concomitant systemic immunosuppressive therapy after subconjunctival
      mitomycin C. Two patients underwent successful visual rehabilitative surgery in
      the mitomycin C-treated eye. CONCLUSION: The use of subconjunctival mitomycin C
      may be effective in preventing progression of conjunctival cicatrization and
      erythema in patients with OCP. No complications of mitomycin C treatment were
      noted. Long-term follow-up and further investigation into the efficacy of
      subconjunctival mitomycin C in the management of OCP is warranted.

PMID- 9917785
TI  - In vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin.
      Emerging resistance.
AB  - OBJECTIVE: To examine in vitro susceptibility of bacterial keratitis pathogens to
      ciprofloxacin. DESIGN: Retrospective review. PARTICIPANTS: The authors examined
      in vitro susceptibility of 1558 corneal isolates from 1303 patients with culture
      proven bacterial keratitis seen at the LV Prasad Eye Institute in Hyderabad,
      India, during the 6-year period between March 1, 1991, and June 30, 1997.
      RESULTS: Of 1558 corneal isolates, 478 (30.7%) were not sensitive to
      ciprofloxacin. Among the isolates, 355 (32.5%) of the 1091 gram-positive cocci
      were not sensitive to ciprofloxacin, and 2 (10%) of the 20 gram-positive bacilli,
      22 (13.3%) of the 165 gram-negative organisms, and 99 (35.1%) of the 282
      Actinomycetes and related organisms were not sensitive to ciprofloxacin. Results
      from chi-square for trends analysis showed a trend of significantly increasing
      ciprofloxacin insensitivity in bacteria between 1992 and 1997 (P = 0.011).
      CONCLUSION: This is the first report of significantly increasing ciprofloxacin
      insensitivity among corneal pathogens. Although the lowered cost and convenience
      of dispensing a single, commercially available antibiotic such as ciprofloxacin
      in the initial treatment of bacterial keratitis is desirable, the emergence of
      ciprofloxacin resistance is a significant finding in this series, and the
      clinician should proceed with caution in the initial empiric treatment of
      bacterial keratitis with ciprofloxacin.

PMID- 9917786
TI  - Periocular atypical mycobacterial infections.
AB  - OBJECTIVE: To examine the clinical characteristics and management of periocular
      infections caused by atypical mycobacteria. DESIGN: Retrospective, noncomparative
      case series. PARTICIPANTS: Six patients were identified with periocular atypical
      mycobacterial infections: four with Mycobacterium chelonae and two with
      Mycobacterium fortuitum. INTERVENTION: The treatment of these infections included
      removal of the foreign bodies with debridement of the lesions. Specimens were
      sent for histopathologic examination, routine cultures, and fresh tissue for
      culture after homogenization. MAIN OUTCOME MEASURES: A retrospective review of
      culture-proven atypical mycobacterial infections involving the periocular tissues
      was performed. Charts were reviewed for age, gender, infectious organism, medical
      history, surgical history, presenting symptoms, clinical features, and treatment.
      RESULTS: Four associations with infection were identified in these patients:
      immunosuppression, nasolacrimal duct obstruction, the presence of a foreign body,
      and a history of recent surgery. All six of the patients had at least one of
      these associations and five of the patients had at least two. Clinical
      characteristics that may distinguish atypical mycobacterial infections from acute
      bacterial infections include subacute presentation, firm nodular lesions, mild
      erythema, mild tenderness, and minimal purulent discharge. All patients had
      resolution of their infections after debridement and several weeks of systemic
      antibiotic therapy guided by susceptibility testing. CONCLUSIONS: Periocular
      atypical mycobacterial infections are uncommon. The clinical history and
      examination can raise the suspicion of this infection by revealing the clinical
      characteristics of these infections. Treatment includes removal of foreign
      bodies, debridement, and long-term systemic antibiotic therapy.

PMID- 9917787
TI  - Perilesional and topical interferon alfa-2b for conjunctival and corneal
      neoplasia.
AB  - OBJECTIVE: To evaluate the role of combined subconjunctival and topical
      interferon alfa-2b (IFN alpha 2b) in the treatment of conjunctival and corneal
      intraepithelial neoplasia (CIN). DESIGN: Noncomparative case series.
      PARTICIPANTS: Six patients with histologically proven CIN or recurrences of
      histologically proven CIN were studied prospectively. INTERVENTION: Patients were
      given a single subconjunctival/perilesional injection of recombinant IFN alpha 2b
      (Schering Plough, Kenilworth, NJ) 3 million international units (IU) in 0.5 ml
      and then started receiving topical interferon drops (1 million U/ml) four times a
      day. Patients were followed weekly until complete resolution of the tumor. After
      1 week, patients with minimal response while receiving topical therapy were
      retreated with perilesional injections three times a week until resolution.
      Patients received topical interferon drops for a month after clinical resolution
      of the lesion. MAIN OUTCOME MEASURES: Patients were followed clinically and
      photographically for evidence of tumor resolution. RESULTS: The authors present a
      series of six patients who were treated successfully with a combination of
      subconjunctival/perilesional and topical IFN alpha 2b. All six patients had
      complete clinical resolution of the CIN lesion within 6 weeks of initiation of
      treatment. In the time of follow-up (average, 7.2 months; range, 2-11 months),
      there have been no treatment failures or recurrences. CONCLUSION: IFN alpha 2b
      may be a viable medical alternative to surgical excision for primary or recurrent
      CIN.

PMID- 9917788
TI  - Primitive neuroectodermal tumor of the orbit in an adult. A case report and
      literature review.
AB  - OBJECTIVE: The authors describe the salient clinical, radiologic, and
      histopathologic features of an orbital primitive neuroectodermal tumor in a 28
      year-old man. This is an extremely rare tumor of the orbit, previously reported
      exclusively in children. DESIGN: Case report. INTERVENTION: Excisional biopsy of
      the tumor en bloc was performed. MAIN OUTCOME MEASURES: Histopathologic
      examination was performed by standard techniques and immunohistochemical stains
      on formaldehyde-fixed, paraffin-embedded tumor tissues. RESULTS: Histologic
      examination of the sections of the tumor showed small, blue, round cells with
      occasional Homer-Wright rosette formations. The tumor cells stained positively
      with neuron-specific enolase and vimentin. CONCLUSIONS: This newly recognized,
      highly unusual peripheral primitive neuroectodermal tumor should be considered in
      the differential diagnosis of hypercellular, small, round cell tumor of the orbit
      in adults.

PMID- 9917789
TI  - Pleomorphic adenocarcinomas of the ciliary epithelium. Immunohistochemical and
      ultrastructural features of 12 cases.
AB  - OBJECTIVE: To examine the immunohistochemical and ultrastructural features of the
      rare pleomorphic adenocarcinomas of the ciliary epithelium (CE). DESIGN:
      Retrospective case series. PARTICIPANTS: The study materials included 12 cases of
      adenocarcinoma of the ciliary epithelium: 9 cases of CE hyperplasia and 3 cases
      of CE adenomas. INTERVENTION: Histologic sections were stained with hematoxylin
      eosin, alcian blue, periodic acid-Schiff, and occasionally with Masson trichrome.
      Additionally, the following immunohistochemical markers were used: Kermix
      (ae1/ae3 + ck1), cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane
      antigen, CAM 5.2, S-100 protein, neuron-specific enolase, glial fibrillary acid
      protein, smooth muscle actin, and vimentin. Five lesions were studied
      ultrastructurally. Clinical data were available in all cases, and follow-up was
      obtained in 9 of the 12 patients. RESULTS: Nine tumors occurred in phthisical
      eyes in adults. The tumor cells were arranged in tubular and solid patterns and
      surrounded by thick basement membrane (BM) material and fibrous stroma.
      Immunohistochemistry (IM) of adenocarcinomas showed positivity with kermix (8 of
      12 lesions), CAM 5.2 (7 of 12), and CK7 (5 of 12). Ultrastructurally, the tumor
      cells were surrounded by a thick, homogeneous, and/or multilaminar BM and
      attached to each other by junctional complexes. CONCLUSIONS: Clinically, this
      intraocular neoplasm should be considered in adults with a longstanding blind eye
      with an epibulbar mass and/or proptosis of recent duration. Fatal cases only
      occurred in tumors with extraocular extension. Adenocarcinomas of CE should be
      differentiated from amelanotic melanoma and metastatic lesions by the presence of
      a thick BM material around the tumor cells and intraocular fibrosis.
      Immunohistochemistry is helpful in differentiating from melanomas but not helpful
      in cases of metastatic carcinomas.

PMID- 9917790
TI  - Methotrexate treatment for sarcoid-associated panuveitis.
AB  - OBJECTIVE: To determine the safety and efficacy of low-dose methotrexate (MTX)
      for sarcoid-associated panuveitis. DESIGN: Retrospective noncomparative case
      series. PARTICIPANTS: Twenty eyes from 11 patients were analyzed. Eight patients
      had sarcoidosis. Three patients were clinically suspected of sarcoidosis despite
      negative laboratory testing. All charts of patients with sarcoidosis and
      idiopathic uveitis seen by the Duke Uveitis Service from 1989 to 1997 were
      retrospectively reviewed. Those with sarcoid-associated or sarcoid-suspected
      panuveitis treated with MTX with a minimum of 6 months of follow-up were studied.
      INTERVENTION: Low-dose MTX was administered to patients weekly and patients were
      followed with serial ophthalmologic and medical examinations. MAIN OUTCOME
      MEASURES: Visual acuity, oral and topical corticosteroid requirements, anterior
      chamber inflammation, and ability to undergo successful cataract extraction were
      used to measure the efficacy of MTX therapy. RESULTS: After MTX treatment was
      initiated, 90% of eyes had preserved or improved visual acuity. Mean initial
      Snellen visual acuity was 20/62 and mean final acuity was 20/40 (P = 0.044). Of
      those patients initially requiring oral corticosteroids, the dosage was decreased
      in 100%, and they were completely discontinued in 86%. The mean initial oral
      corticosteroid dose was 26.6 mg and the mean final dose was 1.5 mg (P = 0.012).
      Topical corticosteroids were decreased in 63% of eyes. The mean initial use was
      once every 1.6 hours, and the mean final use was once every 3.9 hours (P =
      0.001). Ninety-five percent of eyes had stabilized or decreased inflammation. The
      mean initial inflammation score was 1.2, and the mean final score was 0.5 (P =
      0.007). Five of six eyes previously unable to have cataract extraction because of
      uncontrolled inflammation became quiet on MTX and underwent surgery. One hundred
      percent of these eyes had improved vision after surgery. Side effects were mild
      and transient or reversible. CONCLUSION: Low-dose MTX is an effective and safe
      adjunct to treat chronic sarcoid-associated panuveitis.

PMID- 9917791
TI  - Molecular confirmation of carriers for Lowe syndrome.
AB  - OBJECTIVE: To determine the sensitivity and specificity of ocular examination for
      the carrier state of Lowe syndrome in females known to be either carriers or
      noncarriers by direct DNA diagnosis. DESIGN: Nonrandomized cohort study.
      PARTICIPANTS: Thirty-one females at risk for carrying Lowe syndrome in 3
      families. METHODS: Slit-lamp biomicroscopy after pupillary dilation was performed
      by a single observer (RAL) who was masked as to carrier status as determined by
      allele-specific detection of mutations in genomic DNA. RESULTS: Carrier
      assessment predetermined by slit-lamp biomicroscopic examination yielded only one
      false-negative in a young girl 5 years of age and no false-positives among 31
      female members examined. CONCLUSIONS: Slit-lamp examination is a highly accurate
      and sensitive test for carrier detection in Lowe syndrome, particularly in women
      of reproductive age.

PMID- 9917792
TI  - Dominant optic atrophy. Refining the clinical diagnostic criteria in light of
      genetic linkage studies.
AB  - OBJECTIVE: To describe the clinical findings and refine the clinical diagnostic
      criteria for dominant optic atrophy based on eight British families in which the
      diagnosis was confirmed by linkage analysis. DESIGN AND PARTICIPANTS: Case
      series; 92 subjects in 8 pedigrees had both eyes examined. INTERVENTION: Family
      members received a domiciliary examination based on best-corrected visual acuity,
      color vision using Ishihara and Hardy Richter Rand (HRR) plates, confrontation
      field testing using a red target, and optic disc evaluation using a direct
      ophthalmoscope. Genomic DNA was extracted from leukocytes or buccal mucosal cells
      and genotyped using 12 fluorescently labeled microsatellite markers from the
      region 3q27-q29. MAIN OUTCOME MEASURES: Subjects were classified clinically as
      definitely or possibly affected on the basis of the domiciliary examination
      before genetic analysis, and these results were compared with the haplotype
      analysis. RESULTS: Clinically, 43 subjects were identified as definitely
      affected, 4 as possibly affected, and 45 as unaffected. Visual acuity in affected
      subjects ranged from 6/6 to count fingers and declined with age. On genetic
      analysis, a haplotype was identified in each family, which was found in all
      definitely affected members but not in those regarded as unaffected. The four
      possibly affected individuals also bore the haplotype that segregated with the
      disease. CONCLUSIONS: Simple clinical tests are highly efficacious in diagnosing
      dominant optic atrophy. Contrary to accepted criteria, symptoms begin before the
      age of 10 years in only 58% of affected individuals. Visual acuity in affected
      subjects is highly variable. A mild degree of temporal or diffuse pallor of the
      optic disc and minimal color vision defects, in the context of a family with
      dominant optic atrophy, are highly suggestive of an individual being affected,
      even if the visual acuity is normal. This widens the generally accepted
      diagnostic criteria for this disease.

PMID- 9917793
TI  - Identification of BK virus in a patient with acquired immune deficiency syndrome
      and bilateral atypical retinitis.
AB  - OBJECTIVE: To report the clinical and histopathologic characteristics of BK virus
      (BKV) retinitis. DESIGN: Case report. TESTING: The clinical features of bilateral
      retinitis in a 29-year-old homosexual white male with the acquired immune
      deficiency syndrome (AIDS) included focal, mottled fundus pigmentation, and
      haloes, as documented by fundus photography. After death of the patient, the left
      eye was studied by light microscopic and immunohistochemical examination. The
      nested polymerase chain reaction (PCR) was used to detect viral deoxyribonucleic
      acid (DNA) in the right eye and other nonocular tissues. The specificity was then
      confirmed by restriction enzyme analysis. RESULTS: The retina of the left eye
      showed focal necrosis and contained cells with intranuclear staining for the BKV
      VP1 protein. In the right eye, BKV DNA was detected in the retina and other
      tissues by nested PCR. Autopsy showed that BKV infection was also present in the
      brain, kidneys, and peripheral blood mononuclear cells. CONCLUSIONS: A number of
      pathogens may cause retinitis in patients with AIDS. The authors have shown that
      BKV should be included among those pathogens and that some clinical features may
      suggest the presence of BKV retinitis.

PMID- 9917794
TI  - Quantitative cytomegalovirus DNA level in the blood and its relationship to
      cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.
AB  - OBJECTIVE: A pilot study was performed to determine whether relationships exist
      between changes in a quantitative solution hybridization assay for
      cytomegalovirus (CMV) DNA in the blood and development of CMV retinitis,
      development of nonocular CMV disease, or reactivation of pre-existing CMV
      retinitis lesions. DESIGN: Observational case series. PARTICIPANTS: Two groups of
      human immunodeficiency virus-infected patients: 10 CMV antibody-positive patients
      with CD4+ T-lymphocyte counts of less than 50 ml and no CMV disease at baseline
      and 11 patients with CMV retinitis but no extraocular CMV disease at baseline.
      INTERVENTION: Quantitative changes in leukocyte-associated CMV DNA levels were
      observed over time. Anti-CMV therapies were based on clinical findings only. MAIN
      OUTCOME MEASURES: Development of CMV end-organ disease or change in activity of
      pre-existing CMV retinitis lesions was measured. RESULTS: Among patients with no
      CMV disease at baseline, four had CMV disease develop during follow-up (three
      cases of CMV retinitis, one case of presumed CMV esophagitis); all had CMV DNA
      levels greater than 5000 genomes/ml before the onset of CMV disease. The
      remaining six patients had levels less than 5000 genomes/ml throughout follow-up
      (P = 0.05). Among patients with CMV retinitis at baseline, all whose CMV DNA
      blood levels rose more than tenfold had extraocular CMV disease or reactivation
      of CMV retinitis develop. Raised CMV DNA blood levels were not seen in every
      patient with clinical reactivation of CMV retinitis. CONCLUSION: Elevated or
      rising CMV DNA blood levels appear to be associated with the development of CMV
      disease in individuals with low CD4+ T-lymphocyte counts. In patients with CMV
      retinitis, rising levels appear to be associated with the development of
      extraocular CMV disease or reactivation of CMV retinitis. Conversely,
      reactivation of CMV retinitis also may occur in the absence of changes in CMV DNA
      blood levels. Further studies are warranted to determine whether changes in CMV
      blood levels can be used as a guide for preemptive therapy to prevent
      reactivation of CMV retinitis lesions or to help choose between local and
      systemic therapy for management of reactivations.

PMID- 9917795
TI  - Methicillin-resistant Staphylococcus aureus infections after scleral buckling
      procedures for retinal detachments associated with atopic dermatitis.
AB  - OBJECTIVE: To determine the incidence and the clinical course of methicillin
      resistant Staphylococcus aureus as a cause of acute-onset infections in patients
      with atopic dermatitis after a scleral buckling procedures. DESIGN: A
      retrospective chart review. PARTICIPANTS: Two hundred eighty-seven patients (293
      eyes) who underwent scleral buckling procedures to treat rhegmatogenous retinal
      detachments at either Osaka Rosai Hospital or Osaka University Medical School
      between July 1, 1995, and June 30, 1997, participated. Of these, 32 eyes (10.9%)
      were associated with atopic dermatitis. INTERVENTION: Demographic and clinical
      data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: The
      incidence, clinical features, and management of postoperative infections
      associated with methicillin-resistant S. aureus were studied. RESULTS:
      Methicillin-resistant S. aureus infection after scleral buckling procedures was
      identified in 6 (18.8%) of 32 eyes of patients with atopic dermatitis but in only
      1 (0.4%) of the other 261 cases without atopic dermatitis (P < 0.001). The
      average interval from the scleral buckling procedures to the initial onset of
      infection was 8.3 +/- 9.1 days (range, 2-28 days). Bacterial infection and
      inflammation were controlled in four eyes by prompt removal of the infected
      buckle in combination with vancomycin administration. In the other three eyes,
      however, repeat intravitreous injections of vancomycin or emergent vitrectomies
      were required because of the development of endophthalmitis. CONCLUSIONS:
      Methicillin-resistant S. aureus is an important causative pathogen of scleral
      buckling infections, particularly in patients with retinal detachment associated
      with atopic dermatitis. Preoperative evaluation and intraoperative attention to
      contamination are recommended to prevent methicillin-resistant S. aureus
      infections in these patients.

PMID- 9917796
TI  - Atovaquone for the treatment of toxoplasma retinochoroiditis in immunocompetent
      patients.
AB  - OBJECTIVE: To report the results of a phase I trial to evaluate the safety and
      efficacy of atovaquone for the treatment of ocular toxoplasmosis in
      immunocompetent patients. DESIGN: Open label, nonrandomized, prospective,
      clinical trial. PARTICIPANTS: Seventeen immunocompetent patients between the ages
      of 18 and 75 years with clinical and serologic evidence of ocular toxoplasmosis
      participated. INTERVENTION: Treatment of ocular toxoplasmosis with atovaquone
      tablets (750 mg four times a day) for 3 months. Prednisone (40 mg) tablets were
      added on day 3 of treatment and tapered as inflammation resolved. MAIN OUTCOME
      MEASURES: Clinical response and patient tolerance to atovaquone therapy for
      ocular toxoplasmosis. RESULTS: Average follow-up was 10 months. Most patients
      experienced no adverse treatment effects. When present, side effects were usually
      mild and included rash, pruritus, headache, and nausea. With the exception of one
      patient, who discontinued treatment at 6 weeks secondary to persistent epigastric
      discomfort, all patients completed the 12 weeks of therapy. All patients had a
      favorable response to treatment that began within 1 to 3 weeks. Visual acuity was
      stabilized or improved in all patients. Median initial visual acuity was 20/200
      and median final visual acuity was 20/25. In general, atovaquone was well
      tolerated. CONCLUSIONS: Atovaquone is better tolerated than conventional
      antitoxoplasmosis therapy and appears to be at least as effective. Atovaquone is
      a promising alternative for the treatment of ocular toxoplasmosis in
      immunocompetent patients.

PMID- 9917798
TI  - Ocular complications of pediatric bone marrow transplantation.
AB  - OBJECTIVE: To investigate the ocular complications in pediatric bone marrow
      transplantation (BMT) patients. DESIGN: Cross-sectional study. PARTICIPANTS: A
      total of 29 pediatric BMT patients were studied. TESTING: Comprehensive
      ophthalmic check-up, including best-corrected visual acuity, intraocular pressure
      (IOP), Schirmer's test, tear breakup time, and slit-lamp and fundus examinations,
      was performed. MAIN OUTCOME MEASURES: Tear film instability and its related
      complications, IOP, cataract, and fundus lesions were measured. RESULTS: The mean
      age of patients was 9.1 years (range, 1.5-15 years). The mean post-BMT duration
      was 20.2 months (range, 3-54 months). Fifteen patients (51.7%) had tear
      abnormalities. Subconjunctival fibrosis was detected in two patients (6.9%). Dry
      and scaly skin of the eyelids was seen in one patient (3.4%). Lens opacities were
      found in 2 (33.3%) of 6 irradiated patients and 2 (8.7%) of 23 nonirradiated
      patients. Two patients (6.9%) had fundus changes, one with unilateral epiretinal
      membrane and the other with bilateral multiple discrete chorioretinal
      hypopigmented lesions in the middle to peripheral part of the retina. The overall
      complication rates for the anterior and posterior segments were 75.8% and 6.9%,
      respectively. CONCLUSION: Ocular manifestations of BMT in children are not
      uncommon. The most common anterior segment problem is tear dysfunction. Posterior
      segment complications are less common but do exist. High rate of cataract
      formation is reported, and this probably is the most important long-term
      "amblyogenic" problem in these immature eyes. Awareness and management of these
      problems with routine eye examination and early intervention are recommended.

PMID- 9917797
TI  - Retinal detachment in Olmsted County, Minnesota, 1976 through 1995.
AB  - OBJECTIVE: To estimate the incidence of rhegmatogenous retinal detachment (RD) in
      a geographically defined population and to compare the probability of RD in
      residents after cataract extraction with the probability of RD in residents who
      did not have cataract extraction. DESIGN: Rochester Epidemiology Project
      databases were used to perform a retrospective population-based incidence study
      of RD diagnosed between 1976 and 1995 with cohort analyses of the influence of
      risk factors on the occurrence of RD. PARTICIPANTS: The population of Olmsted
      County, Minnesota, participated. MAIN OUTCOME MEASURE: Incidence rates of RD
      adjusted to the age and gender distribution of the 1990 U.S. white population
      were measured. RESULTS: Three hundred eleven incident cases of rhegmatogenous RD
      were identified. The mean annual age- and gender-adjusted incidence rate of
      rhegmatogenous RD was 17.9 per 100,000 persons (95% confidence interval [CI],
      15.9-19.9). For idiopathic rhegmatogenous RD alone, the mean annual age- and
      gender-adjusted incidence rate was 12.6 (95% CI, 10.9-14.3) per 100,000 persons.
      Ten years after phacoemulsification and extracapsular cataract extraction, the
      estimated cumulative probability of RD was 5.5 (95% CI, 3.4-7.6) times as high as
      would have been expected in a similar group of county residents not undergoing
      cataract surgery. CONCLUSIONS: Cataract surgery is associated with a
      significantly elevated long-term cumulative probability of retinal detachment.

PMID- 9917799
TI  - Decisions, decisions.

PMID- 9917800
TI  - Glaucoma after pars plana vitrectomy and silicone oil injection for complicated
      retinal detachments.
AB  - OBJECTIVE: To determine the incidence and associations of glaucoma after pars
      plana vitrectomy (PPV) and silicone oil injection (SOI) for complicated retinal
      detachments and the response to treatment. DESIGN: Retrospective noncomparative
      case series. PARTICIPANTS: A total of 150 eyes of 150 patients who had completed
      a minimum of 6 months of follow-up were included in this study. Analysis included
      clinical records of all consecutive cases of complicated retinal detachment that
      underwent PPV with SOI between July 1991 and February 1996. INTERVENTION:
      Surgical intervention for vitreoretinal pathology included standard three-port
      PPV and additional procedures as appropriate for the retinal pathology, and SOI.
      Procedures for the control of glaucoma were silicone oil removal (SOR),
      trabeculectomy with mitomycin C, cyclocryotherapy, semiconductor diode laser
      contact transscleral cyclophotocoagulation (TSCPC) and anterior chamber tube
      shunt to encircling band (ACTSEB). MAIN OUTCOME MEASURES: Presence of glaucoma
      (predefined as intraocular pressure [IOP] > or = 24 mmHg, which also was > or =
      10 mmHg over the preoperative level, sustained for > or = 6 weeks) and the result
      of medical and surgical management were the main outcome measures. Demographic,
      preoperative, intraoperative, and postoperative parameters including the age of
      the patient, etiology of retinal detachment, refractive status, pre-existing
      glaucoma, aphakia, diabetes mellitus, presence of silicone oil (SO) in the
      anterior chamber, emulsification of SO, rubeosis iridis, and anatomic success
      were evaluated by univariate and multivariate logistic regression analyses to
      assess their predictive value in the causation of glaucoma and to determine
      factors prognosticating response to treatment. RESULTS: The main indications for
      PPV+SOI were proliferative vitreoretinopathy (57%; 85 of 150), proliferative
      diabetic retinopathy (15%; 23 of 150), and trauma (14%, 21 of 150). Glaucoma
      occurred in 60 eyes (40%) at 14 days median (range, 1 day-18 months). Elevation
      of IOP could be attributed directly to SO in 42 (70%) eyes. Glaucoma was
      controlled in 43 (72%) of 60 eyes on treatment (with medicines alone in 30%; SOR
      and medicines in 25%; trabeculectomy with mitomycin C/ACTSEB/cyclocryotherapy or
      TSCPC in 17%); 28% (17 of 60) remained refractory. Independent predictive factors
      for glaucoma on multivariate analysis were rubeosis iridis (odds ratio, 10.76),
      aphakia (odds ratio, 9.83), diabetes (odds ratio, 6.03), SO in anterior chamber
      (odds ratio, 4.74), and anatomic failure (negative risk factor; odds ratio,
      0.11). Poor prognostic factors for the control of glaucoma were SO emulsification
      (odds ratio, 15.34) and diabetes (odds ratio, 6.03). CONCLUSION: Glaucoma is a
      frequent and often a refractory complication of PPV with SOI and has a
      multifactorial etiology. Aggressive medical and surgical management with SOR,
      trabeculectomy with mitomycin C, glaucoma shunts, and cyclodestructive procedures
      shows modest success in controlling IOP.

PMID- 9917801
TI  - Continuous visual field test supervision may not always be necessary.
AB  - OBJECTIVE: To assess the effect of supervision on computerized visual field (VF)
      performance and to determine what patient characteristics predict poor
      unsupervised performance. DESIGN: Randomized, crossover, cross-sectional,
      clinical trial. PARTICIPANTS: Two hundred unselected patients with definite or
      suspect glaucoma or neuro-ophthalmic VF indication participated. INTERVENTION:
      All patients completed two 30-2 tests of one eye on a Humphrey perimeter, one
      with continuous active technician supervision and one without supervision after
      the initial 2 minutes of the test. MAIN OUTCOME MEASURES: Visual field
      reliability and global VF indices were measured. RESULTS: Supervision had a
      positive effect on overall reliability (P = 0.04) but not on individual
      reliability parameters or any of the global VF indices. There was no difference
      between Humphrey Field Analyzers I and II in the need for supervision. Predictors
      of need for supervision were low educational level and a prior test result with
      false-positive responses. Predictors of an unreliable test were advanced age and
      a prior test with a high proportion of fixation losses. CONCLUSION: Supervision
      is necessary for those with risk factors for unsatisfactory perimetry such as
      advanced age, low level of formal education, and prior test results with false
      positive responses or high fixation losses; in the remainder, omission of
      supervision can be considered.

PMID- 9917802
TI  - The future of biothermal engineering.
AB  - This is a report on a three-day workshop held at the Allerton House of the
      University of Illinois. The first day consisted of invited tutorials on topics
      related to biothermal engineering: biological structures, analysis of
      microvascular heat transfer, temperature measurement, cryobiology and
      cryosurgery, burns, and industrial and consumer applications. The rest of the
      workshop consisted of discussions in small groups and in plenary sessions dealing
      with relevant topics. Although the discussions endeavored to be as comprehensive
      as possible, the specific topics were selected by the participants based on their
      expertise and interests. The main areas examined were: Instrumentation, Priority
      applications, Mathematical modeling, Thermal injury. The reliable measurement of
      the temperature distribution inside the living tissue is still the premier
      problem of instrumentation although the measurement of other parameters, such as
      properties, blood perfusion or heat flux, is also of great importance. The most
      important applications are medical, industrial, consumer, agricultural, space,
      and military. The degree of sophistication needed in the analysis of specific
      problems varies a great deal from relatively simple heat conduction models to
      complicated ones including blood perfusion, anisotropy, and the influence of
      large blood vessels. For many applications new experimental data are still
      needed. There have been significant advances in the modeling of living tissue
      with increasing understanding of its thermal behavior. The consensus was,
      however, that the models will always have to be tissue or organ specific and some
      new models are still to be developed.

PMID- 9917803
TI  - Blood perfusion measurements in the canine prostate during transurethral
      hyperthermia.
AB  - Using a thermal pulse decay technique, blood perfusion rates were measured within
      different regions in the canine prostate under normal and hyperthermic conditions
      induced either by the microwave or the radio frequency heating. Results indicate
      that, under the normal condition, the periurethral region is most highly perfused
      with an average rate of 0.60 +/- 0.25 ml/min/gm (n = 4) while the perfusion rate
      is 0.34 +/- 0.22 ml/min/gm (n = 10) in parenchyma. An approximately 3.5 fold
      increase in perfusion from the respective baselines was observed in both regions
      when the local tissue temperature was raised to 41.5 degrees C by the microwave
      heating. Another 0.5 fold increase was found in parenchyma after the tissue was
      further heated to 43.1 degrees C at which oscillatory behaviors in tissue
      temperature have been observed. To further study the cause of these oscillatory
      behaviors, the instantaneous blood perfusion response to changes in local tissue
      temperature was investigated using the radio frequency heating. It has been
      revealed that blood flow acts as a feedback of local tissue temperature in a
      closed control system. The thermally stimulated blood perfusion increase appeared
      to be a function of tissue temperature and its temporal gradient. Results from
      this study have shown experimental evidences of local thermoregulation in the
      prostate during hyperthermia.

PMID- 9917804
TI  - Mathematical simulation of heat transfer process in skin cover at burn injury.
AB  - The results of an investigation regarding the correlation between contact thermal
      burns and temperature profile in skin cover of bioobject are given in this work.
      Simple temperature criterion of burns appearance is determined on the basis of
      modeling of heat transfer process. The physical model of skin and critical
      temperature criterion are suggested for estimation of heat protecting properties
      of material for clothes.

PMID- 9917805
TI  - Optimization of temperature distributions for regional hyperthermia based on a
      nonlinear heat transfer model.
AB  - We describe an optimization process specially designed for regional hyperthermia
      of deep seated tumors in order to achieve desired steady-state temperature
      distributions. A nonlinear three-dimensional heat-transfer model based on
      temperature-dependent blood perfusion is applied to predict the temperature.
      Optimal heating is obtained by minimizing an integral object function which
      measures the distance between desired and model predicted temperatures.
      Sequential minima are calculated from successively improved constant-rate
      perfusion models employing a damped Newton method in an inner iteration.
      Numerical results for a Sigma 60 applicator are presented.

PMID- 9917806
TI  - 3-D temperature distribution in ultrasound hyperthermia with interstitial
      waveguide applicator.
AB  - Knowledge of temperature distribution in thermal treatment of cancerous tissue is
      of primary importance for the therapy success. We discuss here finite element
      analysis approach to obtain 3-D temperature distribution in heating with a four
      applicator array. A comparison of phantom and simulation temperatures indicated
      that inclusion of shear component in heating with ultrasound interstitial
      applicators improves significantly the simulation quality factor. We included
      this component in simulations of 3-D temperature pattern when heating brain
      tissue with the array. The simulations for the tissue show that the perfusion
      remains a primary factor in defining the pattern.

PMID- 9917807
TI  - Computer simulation of heat and mass transfer in tissue during high-intensity
      long-range laser irradiation.
AB  - Three-dimensional transient finite difference numerical model of the biological
      tissue irradiated by powerful laser beam is developed. It is used to simulate the
      thermal behavior of tissue assuming that radiation wavelength is chosen to give
      rise for volumetric heat sources. A three-dimensional seven-flow model is used to
      calculate radiation propagation. Evaporation and burn-out of tissue resulting in
      a through hole along the axis of the beam are taken into account. Besides the
      water boiling and corresponding changes of thermal and optical tissue properties
      the model takes into account one of the heat steam transfer mechanisms. Estimates
      are carried out for the effects of diffusion transfer and vaporization of water
      from the tissue surface. Kinetics of protein denaturation process are calculated
      by Arrenius equation. The problem is solved numerically using discrete grid
      technique and adaptive time-step control algorithm.

PMID- 9917808
TI  - Laser ultrasonic transport of drugs in living tissues.
AB  - This paper deals with non-invasive erbium: yttrium aluminium garnet (Er:YAG)
      laser drug delivery methods, i.e. laser optoacoustic (OA) impregnation, enhanced
      laser OA impregnation, laser injection, and laser OA injection. Preliminary in
      vitro experiments on stratum corneum laser ablation, enhanced diffusion,
      brilliant green laser injection into both gelatinous gel and an autopsy piglet
      skin, and research on laser OA injection have been conducted. The vacuum suction
      mechanism of laser drug injection is discussed.

PMID- 9917809
TI  - On the thermal efficiency of cold-stressed fingers.
AB  - Thermal efficiency of cold-stressed finger-tips during cold induced
      vasodilatation (CIVD) is considered. The actual heat loss from the finger-tip is
      compared to either the minimal or the maximal heat losses. The actual heat loss
      is estimated by integrating the area under the time-temperature curve of the
      finger-tip. The minimal heat loss is estimated by extrapolating an exponential
      approximation of finger-tip temperature until it reaches a certain minimal value.
      The value used in this study is 5 degrees C, which is the pain threshold. The
      maximal heat loss is calculated by assuming finger-tip temperature to be
      maintained at its initial value throughout the cold exposure. These quantities
      were calculated for a series of exposures involving two environmental conditions
      of gloved subjects: Tdry bulb = -17.2 degrees C, Tdew point = -25.1 degrees C
      (cold-dry) and Tdry bulb = 0 degree C, Tdew point = -8.4 degrees C (cold-wet).
      Thermal efficiency was in the range of 0.40-0.85 for the minimal heat loss value
      (eta min) and 0.22-0.72 for the maximal heat loss value (eta max). Weak linear
      relationships between the two definitions of the thermal efficiencies and the
      total duration of the CIVD phase was indicated. The thermal efficiency based on
      minimal heat loss indicated an inverse relation with the total duration of the
      CIVD phase. This contradiction could be reconciled by the application of the
      common concept of "coefficient of performance". Considerable inter- and intra
      subjects variability was found.

PMID- 9917810
TI  - Measurement of thermal diffusivity of bovine aorta subject to finite deformation.
AB  - The flash thermal diffusivity measurement technique is applied to tissue for the
      first time. Making use of its minimal contact with the specimen, the flash
      technique is extended to allow for well-defined, biaxial, finite strain. As an
      example application, the radial component of thermal diffusivity of bovine
      descending aorta is measured in vitro as a function of equibiaxial stretch, at
      room temperature. Data analysis is accomplished using a Marquardt algorithm
      coupled with a finite difference solution of the thermal diffusion equation.
      Extension of this method to measure simultaneously three orthogonal components of
      diffusivity, at different levels of temperature, is discussed.

PMID- 9917811
TI  - The effect of turbulent fluctuation of air on thermal sensation.
AB  - The palm of right hand was alternately exposed to turbulent and laminar flows of
      air with the same velocity, to investigate the effect of turbulent velocity
      fluctuation on thermal sensation. It could be quantitatively shown for the first
      time, by measuring subjective sensations, that the turbulent velocity fluctuation
      had the effect of causing the air temperature to be felt lower than that of the
      laminar flow. The results of heat transfer experiments using an aluminum disk as
      a model of the palm suggested that the difference in thermal sensation for the
      two air flows was generally ascribable to the difference in heat transfer
      coefficient from the skin of the palm caused by the turbulent velocity
      fluctuation. The hypothesis that the temperatures of the turbulent and laminar
      flows of air with the same velocity would be felt the same when heat losses from
      the skin to the two air flows were equal, was supported by the results of these
      experiments.

PMID- 9917812
TI  - Fluid filtration across the arterial wall under flow conditions: is wall shear
      rate another factor affecting filtration rate?
AB  - The effect of flow on fluid filtration across an arterial wall was investigated
      in the canine common carotid artery. The arteries were cannulated in situ to
      maintain their in vivo length and endothelium intact. The excised vessels were
      pressurized at 120 mmHg through an overflow head-tank system that provided a
      constant flow rate to the perfused vessels. Filtration rates across the walls of
      the carotid arteries tested were measured under 4 different experimental
      conditions: 1) albumin-free Krebs solution under absent flow condition; 2)
      albumin-free Krebs solution with flow (148 +/- 8 ml/min); 3) Krebs solution
      containing 1.0 g/dl bovine serum albumin under absent flow condition; 4) Krebs
      solution containing 1.0 g/dl bovine serum albumin with flow (148 +/- 8 ml/min).
      Under absent flow conditions, the addition of albumin to the Krebs solution (1.0
      g/dl) led to an approximate 25% drop in filtration rate (p < 0.001). It was found
      that fluid flow affected the filtration rate of the albumin solution, yet failed
      to affect the filtration rate of albumin-free solution across the arterial wall.
      The present study suggests that the change in filtration rate of the albumin
      solution under flow condition may indicate the change in the luminal surface
      concentration of albumin due to flow.

PMID- 9917813
TI  - Mathematical model for controlled diffusional release of dispersed solute drugs
      from monolithic implants.
AB  - New mathematical models are formulated and analytical solutions are presented for
      the diffusional release of a solute from both non-erodible and biodegradable
      multi-layered slab matrices in which the initial drug loading c0 is greater than
      the solubility limit cs. A Stefan problem with moving boundaries results from
      this formulation. An inward moving diffusional front separates the reservoir
      (unextracted region) containing the undissolved drug from the partially extracted
      region. The cumulative mass released is determined as a function of time. The
      ultimate goal of such an investigation is to provide a reliable design tool for
      the fabrication of specialized implantable capsule/drug combinations to deliver
      prespecified and reproducible dosages over a wide spectrum of conditions and
      required durations of therapeutic treatment. Such a mathematical/computational
      tool may also prove effective in the prediction of suitable dosages for other
      drugs of differing chemical or molecular properties without additional elaborate
      animal testing.

PMID- 9917814
TI  - Structure and growth of tumors: the effect of Cartesian, cylindrical, and
      spherical geometries.
AB  - We present results of numerical simulations of a mathematical model simulating
      mass transfer in the development of a tumor, resulting in its encapsulation and
      lobulation. A modified generation term that reflects the population pressure on
      growth leads to nodular tumor growth. Simulations have been carried out in one
      dimensional Cartesian, cylindrical, and spherical geometries. Important
      differences between the three cases have been found. Simulation results in
      spherical geometry suggest the lobes near the center of the tumor to be larger
      than those near the capsule wall.

PMID- 9917815
TI  - Concentration polarization of low density lipoproteins (LDL) in the arterial
      system.
AB  - The atherogenic lipid concentration at the luminal surface of a blood vessel may
      vary according to its location in the arterial tree because of regional
      differences in wall shear rate, blood pressure, and vascular permeability. We
      therefore hypothesized that these local variations in the luminal surface lipid
      concentration may contribute to the localization of atherosclerosis. To verify
      this hypothesis, the transport of low-density lipoproteins from flowing blood to
      the arterial wall was studied numerically under both steady-state and pulsatile
      flow conditions. Numerical analysis predicted that "concentration polarization"
      of LDL may occur in the arterial system under these conditions. In contrast to
      steady-state flow conditions, the luminal surface LDL concentration varied with
      time in a cardiac cycle. However, its time-average value was slightly higher than
      the corresponding value under steady-state flow conditions. The time-average
      value of the luminal surface LDL concentration was 5 to 14% greater than the bulk
      concentration in a straight segment of an artery. The luminal surface LDL
      concentration at the arterial wall was flow-dependent, varying linearly with the
      filtration rate through the vessel wall and inversely with wall shear rate. This
      may therefore have some significant implications for the pathogenesis and
      localization of vascular disorders.

PMID- 9917817
TI  - Method of designing pre-freezing protocol in cryopreservation of biological
      materials.
AB  - Procedures of determining the pre-freezing protocol in cryopreservation of
      biological materials are discussed. In order to cryopreserve biological
      materials, especially tissues with large sizes, the concentration of
      cryoprotective agents (CPAs) should be high enough after pre-freezing process,
      because a high concentration CPA solution can be vitrified a rather low cooling
      rate. In the pre-freezing process, the concentration of CPA is raised gradually
      to avoid osmotic stress. In this paper, a conventional method of designing the
      pre-freezing protocol is proposed. The rate of increase of the concentration of
      CPA can be calculated on the basis of Kedem-Katchalsky equations using the
      membrane permeabilities, Lp, w and s. Optimal protocol can be determined by
      calculating a process in which the normalized volume of the cell is kept constant
      whole through the process.

PMID- 9917816
TI  - Response of a liver tissue slab to a hyperosmotic sucrose boundary condition:
      microscale cellular and vascular level effects.
AB  - Transport of a non-permeating CPA in liver tissue was studied by experimental and
      theoretical techniques. The system consisted of a 20 mm x 15 mm x 500 microns
      (thick) slab of liver tissue which was exposed to culture media and hyperosmotic
      sucrose (0.3 or 0.6 M) at the boundary. The volumetric changes of cell and
      vascular spaces within the tissue slab at 125 microns from one of the symmetric
      boundaries was studied by slam freezing followed by freeze substitution
      microscopy. The experimental data was then theoretically investigated using two
      models; one based on an effective diffusion coefficient for sucrose, and another
      which incorporated the convective flux of water out of the cells (and the tissue)
      while sucrose diffuses in. We estimate the effective diffusion of sucrose as 16
      33% of the actual diffusivity of sucrose in bulk water. The role of convection of
      water out of the tissue is against the flow of sucrose and appears to be
      important in reducing the effective diffusivity of the sucrose. The role of
      vascular compliance, porosity and tortuosity are also discussed with respect to
      our results.

PMID- 9917818
TI  - A model of low-temperature water transport for hepatocyte spheroids.
AB  - Spheroids are multicellular aggregates that exhibit a more tissue-like morphology
      and function when compared to monolayer cultures of the same cells. Hepatocyte
      spheroids are presently under investigation for use of an artificial liver. The
      ability to cryopreserve hepatocyte spheroids is essential for their clinical and
      commercial application. A multicompartment model was formulated to predict water
      content as a function of temperature during freezing. The theoretical predictions
      of water transport indicate that there will be spatial differences in water
      content of the spheroid during freezing and that due to the rapid decrease in
      water transport with decreasing temperature, the undercooling of the
      intracellular solution during freezing will increase steadily. These results
      indicate that conventional freezing of hepatocyte spheroids will be difficult to
      accomplish due to transport limitations in the spheroids.

PMID- 9917819
TI  - Network thermodynamic model of coupled transport in a multicellular tissue--the
      islet of Langerhans.
AB  - Network thermodynamic modeling via bond graphs was used to describe the water and
      cryoprotectant additive (CPA) transport in a multicellular tissue. The model is
      presented as a tool to understand the osmotic behavior of the islets of
      Langerhans when exposed to ternary aqueous solutions containing an electrolyte
      and a CPA. It accounts for the effects of the location of cells within the tissue
      and an interstitial matrix, plus differential permeabilities to water and CPA.
      The interstitial matrix was assumed to be a porous medium able to store the
      chemical species being transported. Controlled osmotic stress experiments were
      conducted on isolated rat pancreas islets to measure the transient volumetric
      response to step-wise changes in dimethyl sulfoxide, Me2SO, concentration. The
      model provides a tool for predicting the transient volumetric response of
      peripheral and interior cells and of interstitial tissue, as well as the build up
      of solute concentration, during addition and removal of CPAs and freezing and
      thawing protocols. Inverse solution methods were applied to determine values for
      standard cell membrane permeability parameters Lp, omega and sigma as well as for
      the interstitial flow conductivities Kw and Kp'.

PMID- 9917820
TI  - Non-linear microscale alterations in membrane transport by
      electropermeabilization.
AB  - The purpose of this study was to quantify the changes in cell membrane
      conductance in response to electropermeabilization, which may elucidate the
      mechanisms of tissue injury resulting from high-voltage electrical shock. A high
      speed, space-clamp and voltage-clamp experimental configuration was used. The
      pulse parameters of an imposed transmembrane potential that are instrumental in
      membrane properties alteration were precisely controlled. The dynamics of the non
      linear electroporation response was characterized.

PMID- 9917821
TI  - Things we do not know about cryopreservation of biological organs.
AB  - This article is intended to summarize the state-of-the-art of cryopreservation of
      biological organs by raising eight questions to be answered. Brief answers and
      comments are given to each of the questions. Although they never are sufficient
      for complete understanding of the phenomena occurring in cryopreservation, they
      might be useful for letting us know better what we should do next.

PMID- 9917822
TI  - Three-dimensional behavior of ice crystals and biological cells during freezing
      of cell suspensions.
AB  - Behavior of ice crystals and human red blood cells during extracellular-freezing
      was investigated in three-dimensions using a confocal laser scanning
      microscope(CLSM), which noninvasively produces tomograms of biological materials.
      Physiological saline and physiological saline with 2.4 M glycerol were used for
      suspension. Various cooling rates for directional solidification were used for
      distinctive morphology of the ice crystals. Addition of acridine orange as a
      fluorescent dye into the cell suspension enabled ice crystal, cells and unfrozen
      solution to be distinguished by different colors. The results indicate that the
      microscopic structure is three-dimensional for flat, cellular, and dendritic
      solid-liquid interfaces and that a CLSM is very effective in studying three
      dimensional structure during the freezing of cell suspensions.

PMID- 9917823
TI  - Prevention of hemolysis in rapidly frozen erythrocytes by using a laser pulse.
AB  - This paper reports on the successful recovery of rapidly frozen unprotected
      erythrocytes by vitrification of the intracellular solution with a laser pulse
      prior to thawing. Erythrocytes that were frozen at 10,000 degrees C/min exhibited
      100% hemolysis when thawed unless they were first irradiated by a 7 ns. laser
      pulse that selectively targeted the intracellular ice so that it was melted and
      resolidified into a glass phase. Up to 80% of the cells treated in this way
      remained intact after thawing. Wright's staining confirmed a healthy cell
      morphology and the retention of hemoglobin in the laser treated cells. While it
      is well known that small amounts of intracellular ice can be tolerated by cells,
      the findings of this study are the first to indicate that intracellular ice may
      be innocuous even when formed in substantial quantities provided that crystal
      growth and coalescence can somehow be avoided during warming.

PMID- 9917824
TI  - Cryopreservation and transplantation of dog trachea.
AB  - In order to meet the need of trachea transplantation for clinical application, it
      is important to research the methods of cryopreservation and transplantation of
      trachea. By the thermal analyses and thermal control techniques, combined with
      electron microscopy, the effects of cooling and warming rates with different
      concentrations of cryoprotective agents were studied. Also the transplantation
      technique was studied, eighty five percent (17/20) of the dogs were survival
      after the transplantation with cryopreserved tracheas.

PMID- 9917825
TI  - Biophysics of freezing in liver of the freeze-tolerant wood frog, R. sylvatica.
AB  - This study investigates the water transport characteristics during freezing in
      the liver tissue of the freeze-tolerant wood frog Rana sylvatica. Experiments
      were performed using both low temperature microscopy and a differential scanning
      calorimeter (DSC). Tissue samples were cooled at 2 and 5 degree C/min by a "two
      step" freezing technique to end temperatures of -4, -6, -8, -10, and -20 degrees
      C, followed by a slam cooling (> 1000 degrees C/min) step. Stereological analysis
      of the low temperature microscopy results leads to the conclusions that 74% of
      the control tissue is cellular (26% vascular), Vb (osmotically inactive cell
      volume) is 0.4 Vo and the Krogh cylinder dimensions are: distance between
      adjacent sinusoid centers, delta X = 64 microns, original sinusoid (vascular)
      radius, rvo = 18.4 microns and length of the Krogh cylinder, L = 0.71 microns
      (assuming a single isolated hepatocyte cell diameter of 16 microns). A parallel
      study was also done using the DSC at 2 and 5 degrees C/min, and the measured heat
      releases from the tissue were used to calculate water transport data. Both
      techniques confirmed that tissue cooled at 5 degrees C/min does not dehydrate
      completely, but does so when cooled at 2 degrees C/min. By curve fitting a model
      to 5 degrees C/min water transport data from both techniques the biophysical
      parameters of water transport were obtained: Lpg = 1.76 microns/min-atm and ELp =
      75.5 Kcal/mol. A modified Krogh model was used to account for the fact that
      approximately 24% of the hepatocytes were found not to be in direct contact with
      the vasculature. This model was then used to explain the experimentally measured
      water retention in some cells on the basis of different volumetric responses to
      dehydration of cells directly adjacent to vascular spaces and cells at least one
      cell removed from the vascular spaces.

PMID- 9917826
TI  - Sensitivity of kidney perfusion protocol design to physical and physiological
      parameters.
AB  - The introduction and removal of cryoprotective agents (CPA) to a kidney via
      vascular perfusion may induce changes in cell volume that are destructive to the
      tubular epithelial or capillary endothelial cells as well as causing significant
      increases in vascular resistance that compromise the perfusion process. A network
      thermodynamic model of the coupled osmotic, hydrodynamic and elastic properties
      of the kidney was applied to evaluate the sensitivity of these critical outputs
      to a set of physiological and perfusion variables. Simulation results suggest
      that in the design of perfusion protocols for CPAs such as glycerol, it may be
      advantageous to: (a) select a CPA with as high a cell membrane permeability as
      possible; (b) increase the concentration of mannitol in the perfusate to about
      200 mos/kg, beyond which there is no discernible benefit; (c) when glycerol is
      the CPA, limit the rate of reduction in the perfusate during removal to 30 mM/min
      or less; (d) limit the perfusion pressure to 20-30 mm Hg, within the practical
      constraints of the perfusion system; (e) increase the concentration of impermeant
      in the perfusate to as high as 400 mos/kg, although it is recognized that this
      departure from plasma-like composition might impose other problems that are not
      considered in this model. Further, it was observed that the vascular membrane
      permeability plays a relatively minor role in controlling cellular osmotic injury
      and vascular perfusion resistance and is therefore not a critical parameter in
      the perfusion design process.

PMID- 9917827
TI  - Convective heat transfer around an infant head.
AB  - Knowledge of heat and mass transfer between an infant and his environment is
      necessary to control hospital care conditions, or understand a pathology as
      Sudden Infant Death Syndrome (SIDS). This paper precises the particular
      importance of the heat transfer over the head and quantifies the influence of
      various parameters on natural convection heat transfer.

PMID- 9917828
TI  - Morphogenesis of the retinal pigment epithelium: toward understanding retinal
      degenerative diseases.
AB  - The phenotype of an epithelial cell is defined by a unique combination of
      morphology, gene and protein expression, and protein localization. Results
      indicate that the terminal differentiation of the RPE cell can be described in
      part by changes in the polarity of its surface proteins alpha v beta 5 integrin,
      Na,K-ATPase, N-CAM, and EMMPRIN. Changes in protein/gene expression and protein
      localization in late stages of RPE development identify alpha v beta 5 integrin
      as a key player in RPE phagocytosis, and N-CAM and EMMPRIN as potentially
      important molecules in other RPE functions necessary for photoreceptor survival.
      By studying the trafficking of the later two proteins it is shown that entry into
      an apical or basolateral pathway in RPE cells cannot be predicted by the
      distribution of a given protein in other epithelial cells, and that this
      distribution may change through the course of RPE development. The mechanisms
      used by RPE and other epithelia to establish and maintain their specific polarity
      properties are fundamental to the formation and maintenance of their specific
      epithelial phenotype. The ability to therapeutically direct molecules
      incorporated into RPE by gene therapy into apical or basal surfaces requires an
      understanding of protein localization and expression. Furthermore, evidence is
      provided that assays capitalizing on changes in gene/protein expression and
      protein localization during the late stages of RPE development can prove a
      productive way of identifying proteins used by RPE for photoreceptor support.
      This approach can continue to be exploited to identify other proteins essential
      for the mission of the RPE cell, that may thus be likely candidates for
      participation in retinal degenerative disease.

PMID- 9917829
TI  - Formation of the placenta and extraembryonic membranes.
AB  - In eutherian mammals, the first cell types that are specified during
      embryogenesis are committed to form extraembryonic (placenta and fetal membranes)
      rather than embryonic structures. The trophoblast cell lineage, for example,
      forms at the morula-to-blastocyst transition: cells at the periphery of the
      morula become trophoblast, whereas cells on the inside remain undifferentiated
      embryonic ectoderm, which later gives rise to the fetus as well as the endodermal
      and mesodermal components of the placenta and extraembryonic membranes. Genetic
      studies in mice are beginning to identify growth factors and cell adhesion
      molecules that mediate interactions between cell types that are essential for
      morphogenesis of the placenta and fetal membranes, as well as transcription
      factors that control the differentiation of extraembryonic cell types.

PMID- 9917830
TI  - Common molecular pathways in skeletal morphogenesis and repair.
AB  - The formation of bone is a continual process in vertebrate development, initiated
      during fetal development and persisting in adulthood in the form of remodeling
      and repair. The remarkable capacity of skeletal tissues to regenerate has led to
      the hypothesis that the molecular signaling pathways regulating skeletogenesis
      are shared during fetal development and adult wound healing. A number of key
      regulatory pathways that are required for endochondral ossification during fetal
      development are described, and their reintroduction in fracture repair
      demonstrated. Secreted proteins such as Sonic and Indian hedgehog exert their
      effect on pattern formation and chondrogenesis in the appendicular skeleton,
      partly through regulation of molecules such as bone morphogenic proteins (Bmps)
      and parathyroid hormone-related peptide (PTHrP). Once chondrocytes have matured
      and hypertrophied, they undergo apoptosis and are replaced by bone; the
      transcription factor Cbfal plays a critical role in this process of chondrocyte
      differentiation and ossification. Analyses of the expression patterns of these
      genes during fracture healing strongly suggest that they play equivalent roles in
      adult wound repair. Knowledge acquired through the study of fetal skeletogenesis
      will undoubtedly contribute to an understanding of fracture repair, and
      subsequently guide the development of biologically based therapeutic
      interventions.

PMID- 9917831
TI  - Wnt signaling stabilizes the dual-function protein beta-catenin in diverse cell
      types.
AB  - The Wnt proteins constitute a large family of secreted signaling factors that
      performed a wide variety of inductive and regulatory functions in embryonic and
      postnatal development. In mammals, these include crucial roles in morphogenesis
      of the central nervous system, kidneys, limbs, and mammary glands. In recent
      years, much progress has been made in identifying components of the intracellular
      Wnt-1 signal transduction pathway through studies in Drosophila, C. elegans,
      Xenopus, and mammalian systems. Several features of this pathway are remarkably
      well conserved in evolution. A key component of the Wnt pathway is the
      cytoplasmic protein beta-catenin, whose stability is increased as a result of Wnt
      signaling. Although morphological effects of Wnt-1 in cell culture are seen in
      only a limited number of cell lines, we show here that responsiveness to Wnt-1 at
      the biochemical level is a common property of both epithelial and mesenchymal
      cells. The increased abundance of beta-catenin may have at least two functional
      consequences, depending on the subcellular localization of the protein. In some
      cell lines that respond to Wnt-1, there is a significant increase in the beta
      catenin fraction associated with the plasma membrane, where the protein acts as a
      component of cell-cell adhesive junctions. In other cell types, the major effect
      of Wnt signaling is an increase in the cytosolic pool of beta-catenin. Increased
      abundance of this pool has recently been correlated with entry of beta-catenin
      into the nucleus, where the protein forms complexes with Tcf transcription
      factors and is thought to modulate the expression of specific genes. The dual
      consequences of Wnt signaling on cell adhesion and/or gene expression provide at
      least two potential mechanisms by which this key pathway can function in the
      regulation of morphogenesis.

PMID- 9917832
TI  - Molecular cloning and developmental expression of the Xenopus homolog of integrin
      alpha 4.
AB  - Integrin receptors containing an alpha 4 subunit mediate cell-cell adhesion by
      binding to VCAM and MadCAM-1 in addition to supporting cell-extracellular matrix
      (ECM) adhesion by binding to the alternatively spliced V-region of fibronectin
      (FN). Studies in chick and mouse embryos have implicated these integrins in
      neural crest migration, myotube formation, heart development, and placentation.
      Because integrin-FN adhesive interactions have been shown to play essential roles
      in mammalian development, studies were initiated of integrin alpha 4 in amphibian
      embryos, which are better suited to experimental analyses of the earliest stages
      of embryogenesis. Here, the cDNA cloning and pattern of expression of the Xenopus
      laevis homolog of integrin alpha 4 is reported. Xenopus alpha 4 is 55% identical
      at the amino-acid level to both its human and mouse counterparts, including
      conservation of an alpha 4-specific protease cleavage site, 11 potential N-linked
      glycosylation sites, and 24 cysteine residues. In situ hybridization analysis
      reveals that transcripts encoding alpha 4 are expressed in epidermis and the
      branchial arches. Although alpha 4 transcripts can be detected as early as
      gastrulation, the protein is observed only after tailbud stages of development
      and is spatially restricted to the epidermis and gills of tadpole stage embryos.
      From these data it is concluded that Xenopus integrin alpha 4 has structural
      features in common with other vertebrate alpha 4 homologs, but is detected in a
      more restricted tissue distribution during development than alpha 4 in other
      species.

PMID- 9917833
TI  - Endochondral ossification is dependent on the mechanical properties of cartilage
      tissue and on intracellular signals in chondrocytes.
AB  - Skeletal elements are formed either by replacing a performed cartilagenous matrix
      template in a process called endochondral ossification or directly from
      mesenchyme by a process known as membranous ossification. Longitudinal growth of
      bones is achieved by growth plates where calcified cartilage is converted into
      bone. To investigate the role of extracellular matrix as well as intracellular
      signaling pathways in the formation and growth of bone, the genes coding for type
      II collagen and cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein
      kinase (cGK) II, were disrupted. It is demonstrated that loss of Col2a1 or cGKII
      led to abnormal endochondral ossification and skeletal development. In cGKII -/-
      mice, bones derived by membranous ossification developed normally while bones
      derived by endochondral ossification were shortened. This growth defect was not
      associated with a general metabolic disturbance. In Col2a1 knockout mice,
      endochondral ossification was completely absent, whereas membraneous ossification
      was not affected. Despite the defects in bone formation, invasion of blood
      vessels into bone cavities and formation of bone marrow occurred in Col2a1-null
      mice. Taken together, the phenotypes of these two knockout mice show that
      chondrocytes need a well-functioning extracellular matrix scaffold and a normal
      cGMP-signaling system for endochondral ossification to form a normal skeleton.

PMID- 9917834
TI  - Beta-catenin directly induces expression of the Siamois gene, and can initiate
      signaling indirectly via a membrane-tethered form.
AB  - Beta-catenin is shown to directly induce the expression of siamois (a homeobox
      containing gene involved in axial patterning) in a cell-autonomous, protein
      synthesis independent manner. Siamois can thus be considered a direct target of
      beta-catenin signaling in Xenopus. Expression of a portion of the armadillo
      repeat region of beta-catenin via a membrane-tethered fusion protein is shown to
      give similar levels of siamois induction and axis duplication as a free,
      untethered form. Reduction of endogenous free beta-catenin levels by
      overexpression of C-cadherin leads to complete inhibition of signaling by the
      membrane-tethered repeat region. Since the membrane-tethered repeat region is
      unlikely to be bound up by C-cadherin, these results show that the membrane
      tethered beta-catenin relies on endogenous beta-catenin for signaling. We propose
      that the membrane-tethered construct acts by titrating a cytoplasmic inhibitor of
      beta-catenin signaling.

PMID- 9917835
TI  - The PS integrins are required for a regulatory event during Drosophila wing
      morphogenesis.
AB  - The PS1 and PS2 integrins are required for morphogenesis of the adult Drosophila
      wing. Clonal analysis experiments have shown that both integrins are necessary to
      maintain adhesion between the dorsal and ventral wing epithelia. We have found
      that early in wing morphogenesis, the integrins are also required for a
      regulatory event, and this may explain why PS1 and PS2 must be expressed on
      opposite surfaces of the wing at the onset of pupariation. Overexpression of
      integrin subunits during this early phase can lead to separation of dorsal and
      ventral surfaces, and we present evidence here that this dominant phenotype (the
      Blistermaker phenotype) results from a gain of integrin function, as opposed to
      negative interference from free integrin subunits. A possible model for an
      integrin signaling requirement in the wing is discussed.

PMID- 9917836
TI  - Extracellular matrix remodeling during morphogenesis.
AB  - The role of proteinases in extracellular matrix remodeling during the
      developmental program of bone, cartilage, muscle, and epithelial differentiation
      in the mandibular arch during embryogenesis was investigated. ECM changes
      accompany morphogenesis during development. The most dramatic changes occur
      during development of bone and cartilage. The expression of matrix
      metalloproteinases (MMPs) was altered by regulating expression of MMPs by growth
      factors, by inhibiting MMP activity, and by genetic ablation of MMPs. The data
      point to critical roles for MMPs in cartilage development and endochondral bone
      formation. MMPs appear to regulate not only ECM degradation but also programmed
      cell death, cell migration, and invasion during these morphogenic processes. The
      data suggest that matrix metalloproteinases play a pivotal role in the
      morphogenesis of structures derived from epithelium (oral sulcus), somitic
      mesoderm (tongue), and cranial neural crest (Meckel's cartilage).

PMID- 9917837
TI  - Fibronectin and integrins in cell adhesion, signaling, and morphogenesis.
AB  - Fibronectin and integrins play crucial roles in a variety of morphogenetic
      processes, in which they mediate cell adhesion, migration, and signal
      transduction. They induce hierarchical transmembrane organization of cytoskeletal
      and signaling molecules into multimolecular complexes of more than 30 proteins.
      Organization of these complexes is a synergistic process dependent on integrin
      aggregation and occupancy, as well as tyrosine phosphorylation. Integrins also
      cooperate with growth-factor receptors to enhance signaling. Fibronectin and
      integrins induce a variety of downstream effects, including enhanced
      transcription factor activity, induction of over 30 genes (> half novel), and
      altered expression of over 100 proteins. Fibronectin and integrins therefore
      trigger a hierarchy of signaling responses involved in regulating processes
      crucial for normal morphogenesis, including cell adhesion, migration, and
      specific gene expression.

PMID- 9917838
TI  - Structural and genetic analysis of laminin-nidogen interaction.
AB  - High-affinity binding of nidogen to laminins involves a single binding site on
      the laminin gamma 1 chain and is thus a property shared by almost all laminin
      isoforms. This binding mediates the connection of laminins to the collagen IV
      network, perlecan and other proteins and is considered to be an essential step in
      the stabilization of basement membranes. Nidogen binding has been located to a
      single LE module (gamma 1III4) by recombinant analysis. Site-directed mutagenesis
      and X-ray crystallography demonstrated that three amino acids (Asp, Asn, Val) in
      loop a of gamma 1III4 are crucial for binding and are supported by some other
      residues. A restricted complementary binding region seems to exist on nidogen
      domain G3. A mutant laminin gamma 1 chain gene that lacks the region encoding
      gamma 1III4 was prepared in mouse embryonic stem (ES) cells by homologous
      recombination. ES cells homozygous for this defect were shown to assemble laminin
      1 into a cruciform structure and to secrete it properly. Yet the mutant laminin
      failed to associate with nidogen. The mutant ES cells were still able to form
      embryoid bodies with a similar differentiated histology as the wild type.
      Immunofluorescence, however, indicated an impaired deposition of nidogen into
      basement membrane-like structures.

PMID- 9917839
TI  - Modulation of cell-extracellular matrix interactions.
AB  - Changes in extracellular matrix (ECM) structure and composition, such as occur
      during morphogenesis, can have important regulatory effects on cell behavior. Two
      fibronectin (FN)-based systems have been developed to dissect how cells respond
      to different types of ECM. One system mimics the provisional matrix of the wound
      and is composed of FN cross-linked into a fibrin clot matrix. Unlike cells on FN
      alone, cells on an FN-fibrin matrix are smaller with cortical distribution of
      actin filaments and membrane ruffles. Addition of the ECM protein tenascin to the
      FN-fibrin matrix induces a different cell morphology. Thus, matrix composition
      can have profound effects on cell phenotype. Cells also interact with FN while
      assembling it into a fibrillar matrix. Using recombinant FNs, a domain that is
      required for normal progression of FN fibril formation has been identified.
      During assembly of this recombinant matrix, formation of actin stress fibers and
      focal adhesions is delayed, demonstrating that changes in FN matrix structure can
      affect intracellular organization and activation of signaling pathways.

PMID- 9917840
TI  - Morphogenesis of the first blood vessels.
AB  - The initial phase of vessel formation is the establishment of nascent endothelial
      tubes from mesodermal precursor cells. Development of the vascular epithelium is
      examined using the transcription factor TAL1 as a marker of endothelial precursor
      cells (angioblasts), and a functional assay based on intact, whole-mounted quail
      embryos. Experimental studies examining the role(s) of integrins and vascular
      endothelial growth factor (VEGF) establish that integrin-mediated cell adhesion
      is necessary for normal endothelial tube formation and that stimulation of
      embryonic endothelial cells with exogenous VEGF results in a massive "fusion" of
      vessels and the obliteration of normally avascular zones. The second phase of
      vessel morphogenesis is assembly of the vessel wall. To understand the process by
      which mesenchyme gives rise to vascular smooth muscle, a novel monoclonal
      antibody, 1E12, that recognizes smooth muscle precursor cells was used.
      Additionally, development of the vessel wall was examined using the expression fo
      extracellular matrix proteins as markers. Comparison of labeling patterns of 1E12
      and the extracellular matrix molecules fibulin-1 and fibrillin-2 indicate vessel
      wall heterogeneity at the earliest stages of development; thus smooth muscle cell
      diversity is manifested during the differentiation and assembly of the vessel
      wall. From these studies it is postulated that the extracellular matrix
      composition of the vessel wall may prove to be the best marker of smooth muscle
      diversity. The data are discussed in the context of recent work by others,
      especially provocative new studies suggesting an endothelial origin for vascular
      smooth muscle cells. Also discussed is recent work that provides clues to the
      mechanism of vascular smooth muscle induction and recruitment. Based on these
      findings, vascular smooth muscle cells can be thought of as existing along a
      continuum of phenotypes. This spectrum varies from mainly matrix-producing cells
      to primarily contractile cells; thus no one cell type typifies vascular smooth
      muscle. This view of the smooth muscle cell is considered in terms of a
      contrasting opinion that views smooth muscle cell as existing in either a
      synthetic or proliferative state.

PMID- 9917841
TI  - The significance of matrix metalloproteinases during early stages of tumor
      progression.
AB  - Matrix metalloproteinases (MMPs) orchestrate tissue remodeling and play diverse
      roles during organ development. They are produced excessively during the course
      of various pathological conditions, including solid tumors. An important function
      of MMPs during tumor progression is to provide the proteolytic activity that is
      necessary both for tumor cells to invade extracellular matrix (ECM) and for
      neovascularization of tumor tissue by endothelial cells. Recently, independent
      studies in transgenic animals suggest that MMPs may, in addition, promote very
      early stages of tumor progression. To investigate this possibility further, we
      have analyzed the consequences of MMP overexpression in functionally normal and
      nontumorigenic mouse mammary epithelial cells in culture. Our observations
      demonstrate that the MMP stromelysin-1 (SL-1) triggers an epigenetic molecular
      program in mammary epithelial cells that results in a number of phenotypic
      alterations that eventually culminate in the generation of a malignant tumor-cell
      phenotype.

PMID- 9917842
TI  - Laminin isoforms and epithelial development.
AB  - Several different approaches suggest that basement-membrane assembly is important
      for epithelial development. Basement membranes contain isoforms of collagen IV,
      proteoglycans, and noncollagenous glycoproteins such as the laminins and
      nidogens. The expression and role of laminins for epithelial morphogenesis is
      reviewed. Laminins are large heterotrimeric proteins composed of alpha, beta, and
      gamma chains. Many major epithelial laminins and their receptors have been
      identified recently, and the extracellular protein-protein interactions that
      drive basement-membrane assembly are beginning to be understood. Three laminin
      alpha-chains are typically made by epithelial, alpha 1, alpha 3, and alpha 5.
      Three major epithelial heterotrimers can at present be distinguished--laminin-1
      (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), and laminin-10
      (alpha 5 beta 1 gamma 1)--but other heterotrimers may exist in epithelia.
      Laminins containing either alpha 1 or alpha 3 chains are largely limited to
      epithelia, whereas the alpha 5 is also found in endothelial and muscle basement
      membranes, particularly in the adult. Some epithelial cell types express several
      laminin alpha-chains, so it is relevant to test how the different laminins affect
      epithelial cells. Laminins interact with integrin type of receptors on the cell
      surface, but binding to other proteins has also recently been demonstrated. Two
      important recent discoveries are the identification of dystroglycan as a major
      laminin receptor in muscle and epithelia, and nidogen as a high-affinity laminin
      binding protein important for basement-membrane assembly. Antibody perturbation
      experiments suggest that these protein-protein interactions are important for
      epithelial morphogenesis.

PMID- 9917843
TI  - There is binding of collagen IV to beta 1 integrin during early skin basement
      membrane assembly.
AB  - This study is concerned with the mechanism of basement membrane assembly in an in
      vitro 3-dimensional skin-culture system. Dermal fibroblasts alone can synthesize
      collagen IV, perlecan, and nidogen, but cannot assemble them into a basement
      membrane. When keratinocytes are added to the culture, however, linear assembly
      of collagen IV, perlecan, and nidogen is noted at the epidermo-dermal interface.
      Northern blots and in situ hybridization showed that perlecan and nidogen mRNAs
      derive exclusively from fibroblasts, while the alpha 2 (IV) collagen chain is
      expressed by both keratinocytes and fibroblasts, although the major source is in
      the mesenchyma (80%). Prior to the development of the lamina densa, collagen IV
      colocalizes with beta 1 integrins, most likely alpha 1 beta 1 and alpha 2 beta 1,
      which are known receptors for this collagen. Blocking experiments with the AIIB2
      mAb (anti-beta 1 integrin subunit) and by peptide inhibition with the CB3(IV)
      collagen fragment disrupted the assembly of collagen IV. This study suggests that
      the initiation of basement-membrane formation involves binding of collagen IV
      molecules to keratinocyte cell-matrix integrins. These complexes act as
      nucleation sites for further polymerization of collagen IV molecules mostly
      derived from fibroblasts, by a process of self-assembly.

PMID- 9917844
TI  - A single disulfide bridge (Cys182-Cys264) is crucial for alpha-dystroglycan N
      terminal domain stability.

PMID- 9917846
TI  - Retinoic acid modulates the expression of integrins in rat sternal chondrocytes
      in vitro.

PMID- 9917845
TI  - Collagen-PVP accelerates new bone formation of experimentally induced bone
      defects in rat skull and promotes the expression of osteopontin and SPARC during
      bone repair of rat femora fractures.

PMID- 9917847
TI  - The spatial pattern of integrins during development of mouse articular cartilage.

PMID- 9917848
TI  - Drosophila oogenesis: a model system to understand TGF-beta/Dpp directed cell
      morphogenesis.

PMID- 9917849
TI  - Patterning of morphogenetic cell behaviors in neural ectoderm of Xenopus laevis.

PMID- 9917850
TI  - Regulation of chondrogenesis in the developing inner ear: a role for sonic
      hedgehog.

PMID- 9917851
TI  - Analysis of the role of dystroglycan in early postimplantation mouse development.

PMID- 9917852
TI  - LCCS: a lethal motoneuron disease of the fetus maps to chromosome 9q34.

PMID- 9917853
TI  - Organogenesis by desired metaplasia of autogenous stem cells.

PMID- 9917854
TI  - Apoptosis fenestrates chick cloacal membrane and occluded rectal cord and may
      have a minor role in removal of pharyngeal membranes.

PMID- 9917855
TI  - An autocrine function for transforming growth factor beta 3 in the
      atrioventricular endocardial cushion tissue formation during chick heart
      development.

PMID- 9917856
TI  - Bone morphogenetic protein 2 acts synergistically with transforming growth factor
      beta 3 in endothelial-mesenchymal cell transformation during chick heart
      development.

PMID- 9917857
TI  - Laminin alpha chains in developing tooth.

PMID- 9917858
TI  - The targeted deletion of the LAMC1 gene.
AB  - Laminin is required for the production of a basement membrane in both the early
      embryo and in the embryoid body. The absence of the gamma 1 chain leads to
      different processing of the other subunits in the trimer and prevents the
      production of a polymerizing laminin molecule. Collagen IV and perlecan are not
      able to compensate for the loss of the laminin molecule, and nidogen, which would
      normally bind to the gamma 1 chain, is almost completely lost from the embryoid
      body. In the embryo the failure of the basement membrane results in embryonic
      lethality at embryonic day 5.5, a time when the primitive endoderm is
      differentiating to visceral and parietal endoderm, and the latter is migrating
      out of the inner cell mass over the trophectoderm. It is likely that failure in
      one or both of these events leads to the death of the embryo. The absence of the
      trophectodermal basement membrane normally present in the blastocyst appears not
      to be necessary for the formation of the blastocystic cavity, which depends on
      the formation of a polarized epithelium. Hence the first epithelium produced in
      the developing embryo does so independently of a basement membrane.

PMID- 9917859
TI  - Interleukin-1 beta, interleukin-18, and the interleukin-1 beta converting enzyme.
AB  - When injected intravenously into humans and animals, interleukin-1 beta (IL-1
      beta) is perhaps the most potent of the endogenous pyrogens. However, IL-1 beta
      is initially synthesized as a relatively inactive precursor molecule (proIL-1
      beta) which lacks a signal peptide and hence remains inside the cell. To be
      active as a fever-producing molecule, proIL-1 beta must first be processed to an
      active mature molecule and secreted. Although several enzymes associated with
      inflammatory tissues are capable of processing proIL-1 beta into an active
      molecule in the extracellular compartment, the IL-1 beta converting enzyme (ICE,
      also called caspase-1) cuts intracellular proIL-1 beta after the aspartic acid
      residue in position 116, resulting in a highly active mature IL-1 beta that is
      secreted into the extracellular space. IL-18 is also initially synthesized as an
      inactive precursor molecule (proIL-18) lacking a signal peptide. IL-18 is a
      member of the IL-1 family, and like IL-1 beta, proIL-18 is cleaved by ICE to
      yield an active molecule. However, unlike IL-1 beta, IL-18 is not an endogenous
      pyrogen following intraperitoneal injection into mice. Nevertheless, IL-18 may
      contribute to inflammation and fever because IL-18 is a potent inducer of tumor
      necrosis factor, chemokines, and interferon-gamma production.

PMID- 9917861
TI  - Immunomodulatory properties of interferon-gamma. An update.
AB  - During the early aspecific phase of host defense, production of interferon (IFN)
      gamma by natural killer cells plays an important role in bringing about acute
      inflammation, mainly because of the activating effects of IFN-gamma on adhesive
      properties of endothelial cells and on mediator production by mononuclear
      phagocytes (MPCs). In the subsequent antigen-specific phase of the immune
      response, IFN-gamma acts as a regulator of antigen presentation and of
      proliferation and differentiation of lymphocyte populations. Immunosuppressive as
      well as immunostimulatory effects may result from these actions. High-level
      production of IFN-gamma during this phase of host defense is now classically seen
      as a hallmark of a T-helper 1 (TH1)-type reaction, characterized by activation of
      antimicrobial activity of macrophages and by inflammatory reactions with a DTH
      character. Development of TH1-type lymphocyte populations producing IFN-gamma is
      regulated by other cytokines including interleukin (IL)-12. In many systems IL-12
      and IFN-gamma act in a similar fashion, and a current subject of debate is the
      question of whether all activities of IL-12 are mediated by IFN-gamma. Another
      question is whether IFN-gamma, by its ability to potentiate MPCs' ability to
      produce IL-12, plays a role in bringing about or stabilizing TH1 type responses.
      In two model systems of autoimmune disease, experimental autoimmune
      encephalomyelitis and collagen-induced arthritis, IL-12 and IFN-gamma were found
      to act independently.

PMID- 9917860
TI  - Interleukin-11. A gp130 cytokine.
AB  - Interleukin (IL)-11 is a member of the gp130 family of cytokines. Comparison of
      IL-11 with another gp130 family member, IL-6, indicates that these two cytokines
      share many overlapping signal transduction mechanisms. However, unlike IL-6,
      treatment of patients with a recombinant human form of IL-11 (rhIL-11) does not
      increase body temperature, suggesting significant differences in the in vivo
      function of these two molecules. Recent studies demonstrate that IL-11 has potent
      anti-inflammatory activity in a variety of preclinical animal models of disease.
      rhIL-11 reduces production of proinflammatory mediators such as tumor necrosis
      factor-alpha and IL-12 from activated macrophages. This effect on proinflammatory
      cytokine production is mediated at the transcriptional level by inhibition of the
      transcription factor, NF- kappa B. To further understand the anti-inflammatory
      mechanisms of action of rhIL-11 and to elucidate differences between IL-11 and IL
      6 signal transduction pathways, the effects of these two cytokines on in vitro
      macrophage function were compared.

PMID- 9917862
TI  - IL-6 and IL-1 beta in fever. Studies using cytokine-deficient (knockout) mice.
AB  - Previous data support the hypothesis that during inflammation, interleukin (IL)-1
      beta and IL-6 are involved in fever, in activation of the hypothalamic-pituitary
      adrenal (HPA) axis, and in the induction of eicosanoids. Most of the
      pathophysiologic effects of IL-1 beta and Il-6 are mediated by prostaglandins
      (PGs), modulated by other cytokines, and antagonized by glucocorticoids (GC), a
      final product of the HPA axis. To further test these relationships, we measured
      changes in body temperature using biotelemetry in mice deficient in genes for IL
      1 beta and/or IL-6 (IL-1 beta knockout [KO] and IL-6 KO) following injection with
      lipopolysaccharide (LPS) to induce systemic inflammation or turpentine to induce
      local abscess. Circulating IL-6, tumor necrosis factor alpha (TNF-alpha), GC, and
      PGE2 were measured in these mice after treatment. IL-1 beta KO mice responded
      with reduced fever and IL-6 KO mice with normal fever to a high dose of LPS. In
      contrast, neither type of KO mice produced fever to turpentine. PGE2 levels
      (measured in the circulation) were suppressed in both types of KO mice injected
      with turpentine. IL-1 beta KO mice showed deficiency in IL-6 following
      turpentine, but not LPS, injection. LPS-induced increases in TNF-alpha did not
      differ between IL-1 beta KO mice and their wild-type counterparts, whereas IL-6
      KO mice showed exacerbated LPS-induced circulating TNF-alpha. No differences were
      noted in plasma elevations of GC between KO and wild-type mice following
      injection of LPS or turpentine, indicating that IL-1 beta and IL-6 are not
      required for activation of the HPA axis during inflammation. Our data demonstrate
      that in the mouse, IL-1 beta and IL-6 are critical for the induction of fever
      during local inflammation, whereas in systemic inflammation they appear only to
      contribute to fever.

PMID- 9917863
TI  - Delineation of the proinflammatory cytokine cascade in fever induction.
AB  - Bacterial lipopolypolysaccharide (LPS)-induced fever involves induction of the
      proinflammatory cytokines interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis
      factor-alpha (TNF-alpha), and IL-6, both in the periphery and in the brain. These
      molecules can induce expression of each other and also regulate expression of
      their own receptors in a complex manner. The functional hierarchy of these highly
      inducible proteins is therefore difficult to determine. Using mice strains
      carrying the null mutations of IL-1 beta, IL-1RI, IL-1RAcP, or IL-6,
      respectively, we show that LPS-induced fever involves IL-1 beta, which acts at a
      complex consisting of the type I IL-1 receptor and the IL-1RAcP. This action
      occurs prior to central IL-6 release, which has been shown to be a necessary
      component of fever responses induced by LPS, IL-1 beta, and also TNF-alpha. In
      the absence of IL-1 beta, as in IL-1 beta-deficient mice, LPS, IL-1 alpha, and IL
      1 beta cause hyperresponsive fevers when exogenously applied. Murine TNF-alpha is
      a poor pyrogen in mice even when mice are kept at thermoneutral temperature (30
      degrees C). TNF-alpha-mediated fever depends on central IL-6 expression.

PMID- 9917864
TI  - Vasopressin-induced antipyresis. Sex- and experience-dependent febrile responses.
AB  - There is now good evidence that vasopressin (AVP) acts, in the male rat, as a
      neurotransmitter in the ventral septal area to reduce fever. In light of the well
      known sexual dimorphism in the AVP innervation of the brain, we asked if female
      rats would (a) display fevers different from those seen in male rats, (b) respond
      to AVP with antipyresis, (c) display evidence of endogenous AVP-induced
      antipyresis during fever, and (d) display altered fevers and AVP involvement as a
      function of hormonal status. Our experiments indicate that female rats display
      larger fevers to intracranial prostaglandin E2 (PGE2) but not to systemic
      lipopolysaccharide or interleukin-1 beta than do male rats. The larger fevers may
      be due, in part, to a lack of AVP-induced antipyresis, as an AVP antagonist
      elevates PGE2 fever in male but not in female rats and dialysates of the ventral
      septal area show increased AVP levels only in male rats during defervescence.
      Nonetheless, females respond to exogenous AVP with antipyresis. Throughout late
      pregnancy, parturition, and lactation, PGE2 fevers are reduced, but this appears
      to be due to a general suppression of autonomic output not involving enhanced AVP
      antipyresis. Fevers due to lipopolysaccharide and interleukin-1 beta are also
      suppressed at this time, and in some animals, fevers are dramatically suppressed
      at about the time of parturition. Our results indicate that female rats may
      utilize different strategies for antipyresis than do male rats and that hormonal
      status may influence both peripherally generated and centrally activated fevers.

PMID- 9917865
TI  - Peptide modulation of fever and inflammation within the brain.
AB  - The importance of melanocortin peptides to host responses was recognized with the
      observation of the antipyretic effect of centrally administered alpha-melanocyte
      stimulating hormone (alpha-MSH). It is now clear that this neuropeptide also
      exerts remarkable antiinflammatory activity via direct actions on peripheral host
      cells, descending neurogenic antiinflammatory pathways stemming from CNS
      melanocortin receptors, and local actions on receptors that control inflammation
      within the brain. Recent studies of the latter influence indicate that alpha-MSH
      inhibits brain tumor necrosis factor-alpha (TNF-alpha), previously linked to
      human neurodegenerative diseases, induced by local injection of
      lipopolysaccharide. Ischemia/reperfusion of the brain, a model of stroke, induces
      inflammation marked by disturbance of CNS function. alpha-MSH given systemically
      modulates disturbances of auditory evoked potentials induced by
      ischemia/reperfusion in the posterior circulation. Such influences of the peptide
      may occur through inhibition of inflammatory agents produced by glia: alpha-MSH 1
      13 and 11-13 modulate TNF-alpha and nitric oxide produced by activated murine
      microglia, and TNF-alpha produced by human astrocytes. Because glia can secrete
      alpha-MSH and express melanocortin receptors, they may, like peripheral
      macrophages, contain autocrine regulatory circuits based on the peptide. alpha
      MSH thus modulates both fever and inflammation in the brain by acting on local
      melanocortin receptors.

PMID- 9917866
TI  - Role of IL-10 in inflammation. Studies using cytokine knockout mice.
AB  - Interleukin-10 (IL-10) inhibits the synthesis of proinflammatory cytokines known
      to be involved in fever, including IL-1, IL-6, and tumor necrosis factor-alpha.
      We hypothesized that IL-10 modulates lipopolysaccharide (LPS)-induced fever in
      mice. Body temperature was measured by biotelemetry. Swiss Webster mice injected
      with recombinant murine IL-10 (rmuIL-10) were resistant to fever induced by a low
      dose of LPS (100 micrograms/kg, i.p.) and to the hypothermic and febrile effects
      of a high (septic-like) dose of LPS (2.5 mg/kg, i.p.). Injection of rmuIL-10
      alone had no effect on afebrile body temperature of Swiss Webster mice. IL-10
      knockout mice showed an exacerbated and prolonged fever in response to a low dose
      of LPS (50 micrograms/kg, i.p.) compared to their wild-type counterparts. These
      data support the hypothesis that IL-10 acts as an endogenous cryogen during LPS
      induced fever in mice.

PMID- 9917867
TI  - Prostaglandin E2 in the pathogenesis of fever. An update.
AB  - Prostaglandin E2 (PGE2) is recognized as a key intermediate in the sequence of
      events leading to fever. Normally undetectable or barely detectable in brain, it
      rises selectively on exposure to an infectious noxa and the attendant generation
      of pyrogenic cytokines outside and, in the case of interleukin (IL)-6, inside the
      brain. The mechanism by which pyrogens in the circulation promote the appearance
      of PGE2 within the confines of brain is not clear, and it is not known how PGE2
      activation is selective with IL-6 being induced in brain. We have found that the
      cerebral microvasculature is not suitable as a source of PGE2 in response to
      blood-borne pyrogens. In addition, we show that IL-6 differs from other pyrogens
      in being able to stimulate specifically PGE2 synthesis. Nevertheless, brain
      derived IL-6 does not appear to be necessary for PGE2 activation and the
      attendant fever. We conclude that signal-transducing mechanisms operating across
      the blood-brain barrier are most critical for the development of the febrile
      response to a systemic noxa.

PMID- 9917868
TI  - Cytokines and fever. Mechanisms and sites of action.
AB  - The cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha
      induce increases in body temperature via direct and indirect actions on the brain
      and are believed to act as endogenous pyrogens. We studied the mechanisms of
      action of these cytokines on fever in rats. Local administration of
      lipopolysaccharide (LPS) into a subcutaneous air pouch elicits marked fever,
      accompanied by increases in the levels of TNF-alpha, IL-1, and IL-6 in the pouch,
      but only IL-6 in the plasma. Thus, TNF-alpha and IL-1 probably act locally to
      stimulate the release of a secondary circulating mediator(s) (e.g., IL-6) that
      can interact with the brain. Neural afferents have also been implicated in
      relaying messages to the brain. Pyrogenic responses are reportedly attenuated by
      subdi-aphragmatic vagotomy; however, we failed to observe inhibition of fever in
      vagotomized rats injected with either LPS or a pyrogenic dose of IL-1, although
      behavioral responses are abolished.

PMID- 9917869
TI  - Neurobiological basis of fever.
AB  - Fever is a coordinated endocrine, autonomic, and behavioral response organized by
      the brain in response to inflammatory stimuli. We examined the mechanism of the
      febrile response to intravenous lipopolysaccharide (LPS) in the rat. LPS caused
      activation of microglia and tissue macrophages in the meninges and along
      penetrating blood vessels. The microglia produce cytokines, such as tumor
      necrosis factor-alpha, and cyclooxygenase type 2. The latter produces
      prostaglandins, which may cross the blood-brain barrier. We found that inhibition
      of COX at the preoptic area prevented fever, whereas injection of PGE2 at this
      site produced fever. Either i.v. LPS or PGE2 into the preoptic area activated a
      specific set of pathways, including the ventromedial preoptic area, which we
      believe to be a key regulatory site, and the paraventricular nucleus, which we
      believe produces autonomic and endocrine responses that cause elevation of body
      temperature. We hypothesize that the pathway connecting these two sites involves
      a double inhibitory relay through temperature-sensitive GABAergic neurons in the
      hypothalamus. This pathway would essentially "turn up the thermostat" during a
      fever, causing an increase in body temperature via normal thermoregulatory
      pathways.

PMID- 9917871
TI  - Hypothalamic neurons. Mechanisms of sensitivity to temperature.
AB  - Rostral hypothalamic neurons are influenced by endogenous factors that affect
      thermoregulation and fever. Intracellular recordings reveal the synaptic and
      intrinsic mechanisms responsible for neuronal thermosensitivity. Many temperature
      sensitive and temperature-insensitive neurons display a depolarizing prepotential
      that precedes action potentials. Temperature has little effect on the
      prepotential of insensitive neurons; however, in warm-sensitive neurons, the
      prepotential's depolarization is elevated by warming, and this increases the
      firing rate. Intracellular cAMP can increase neuronal thermosensitivity by
      enhancing the thermal response of the prepotential, most likely by
      thermosensitive ionic conductances. Warm-sensitive neurons also receive
      inhibitory synaptic input (IPSPs) from temperature-insensitive neurons, enhancing
      the thermosensitivity of some neurons, because cooling increases IPSP amplitude
      and duration. Therefore, even though IPSP frequencies do not change, cooling can
      decrease firing rates by increasing IPSP amplitudes. Because endogenous factors
      change neuronal firing rate and thermosensitivity, these changes likely occur
      both post- and presynaptically as well as by ionic conductances that determine
      the time interval between action potentials.

PMID- 9917870
TI  - Afferent pathways of pyrogen signaling.
AB  - We and others recently showed that fever induced by intravenously or
      intraperitoneally injected lipopolysaccharide (LPS) may involve brain signaling
      via hepatic vagal afferents. This suggests that LPS fever may be initiated by
      mediators released mainly by cells in the liver, presumably macrophages (Kupffer
      cells, Kc). To verify this possibility, we disabled the Kc of conscious guinea
      pigs with gadolinium chloride and monitored their core temperature and associated
      preoptic prostaglandin E2 (PGE2) responses to i.v. LPS. Gadolinium chloride
      pretreatment significantly attenuated both the febrile and PGE2 rises, thus
      supporting the hypothesis. Additionally, fluorescein-labeled LPS was detected in
      Kc 15 minutes after its i.v. administration. Paradoxically, however, the label
      was also present in gadolinium chloride-pretreated guinea pigs. Thus, either Kc
      are not the primary source of pyrogenic mediators or LPS does not provide the
      stimulus for their production. Because the i.v. injection of LPS elicits
      virtually immediately the production of complement fragments, and Kc express
      their receptors and produce various mediators on their activation, we
      hypocomplemented guinea pigs with cobra venom factor. The core temperature rises
      produced by i.v. LPS were reduced by complement depletions > 60%. LPS i.v. per se
      decreased complement, that is, complement was consumed by 12% within 10 minutes.
      Thus, the onset of LPS fever may involve complement system and Kc activation, but
      their precise roles await clarification.

PMID- 9917872
TI  - Tolerance to pyrogens.
AB  - In humans or experimental animals, the repeated confrontation with
      lipopolysaccharides (LPS) from gram-negative bacteria, but not with muramyl
      dipeptide (MDP) from gram-positive bacteria, leads to attenuation of almost all
      pathophysiologic effects mediated by proinflammatory cytokines. Our experiments
      in guinea pigs and rats demonstrate that attenuation of the febrile response
      during the development of LPS tolerance is associated with a reduced production
      of cytokines rather than a decrease in responsiveness to cytokines. Cross
      tolerance experiments demonstrate that different stimuli influencing LPS-induced
      tumor necrosis factor (TNF) release and nitric oxide (NO) synthesis can modify
      the development of tolerance. On the other hand, the lack of cross-tolerance
      between LPS and MDP indicates that MDP can activate the cytokine cascade and
      induce the febrile response in animals tolerant to LPS. This may indicate
      distinct receptors and signal pathways for LPS and MDP, leading to activation of
      the cytokine cascade. LPS tolerance has also been demonstrated in ex vivo and in
      vitro studies. In cultures of monocytes, diminished synthesis of TNF and NO
      reported after LPS restimulation could be prevented and reversed by interferon
      and granulocyte-macrophage colony-stimulating factor. These findings add an
      additional hypothesis in tolerance development.

PMID- 9917873
TI  - Molecular basis of sickness behavior.
AB  - Peripheral and central injections of lipopolysaccharide (LPS), a cytokine
      inducer, and recombinant proinflammatory cytokines such as interleukin-1 beta (IL
      1 beta) induce sickness behavior in the form of reduced food intake and decreased
      social activities. Mechanisms of the behavioral effects of cytokines have been
      the subject of much investigation during the last 3 years. At the behavioral
      level, the profound depressing effects of cytokines on behavior are the
      expression of a highly organized motivational state. At the molecular level,
      sickness behavior is mediated by an inducible brain cytokine compartment that is
      activated by peripheral cytokines via neural afferent pathways. Centrally
      produced cytokines act on brain cytokine receptors that are similar to those
      characterized on peripheral immune and nonimmune cells, as demonstrated by
      pharmacologic experiments using cytokine receptor antagonists, neutralizing
      antibodies to specific subtypes of cytokine receptors, and gene targeting
      techniques. Evidence exists that different components of sickness behavior are
      mediated by different cytokines and that the relative importance of these
      cytokines is not the same in the peripheral and central cytokine compartments.

PMID- 9917874
TI  - Individual variation in hypothalamus-pituitary-adrenal responsiveness of rats to
      endotoxin and interleukin-1 beta.
AB  - Intraperitoneal (i.p.) administration of lipopolysaccharide (LPS) or interleukin
      (IL)-1 beta induces activation of the hypothalamus-pituitary-adrenal (HPA) axis.
      In some experiments, a marked individual variation has been observed in HPA
      responses to these stimuli. We reasoned that only parameters that correlate with
      this variability may reflect signals involved in HPA activation. Although IL-1
      beta is found in the peritoneal cavity and has been implicated in the HPA
      response to i.p. LPS, IL-1 beta levels in peritoneal lavage fluid did not
      correlate with the variation in HPA responsiveness and neither did IL-1 beta
      concentrations in plasma. In contrast, IL-6 concentrations in plasma, but not in
      peritoneal lavage fluid, correlated with this variation to i.p. LPS or IL-1 beta.
      We conclude that IL-6 in the plasma represents a major determinant of the
      individual variation in HPA responses to i.p. LPS or IL-1 beta. Because of its
      positive correlation with Fos expression in various brain-stem nuclei, we suggest
      that circulating IL-6 may facilitate the generation of signals in vagal afferents
      or potentiate vagal information transfer to lower brain-stem nuclei.

PMID- 9917875
TI  - Sleep. A physiologic role for IL-1 beta and TNF-alpha.
AB  - Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are
      involved in physiologic sleep regulation. Administration of exogenous IL-1 beta
      or TNF-alpha induces increased non-rapid eye movement sleep (NREMS). Inhibition
      of IL-1 or TNF reduces spontaneous sleep. There is a diurnal rhythm of TNF-alpha
      mRNA and IL-1 beta mRNA in brain with highest levels occurring during peak sleep
      periods. Mice lacking either the TNF 55-kD receptor or the IL-1 type I receptor
      sleep less than do strain controls. IL-1 beta and TNF-alpha are part of a larger
      biochemical cascade involved in sleep regulation; other somnogenic substances in
      this cascade include growth hormone-releasing hormone and nitric oxide. Several
      additional substances are involved in inhibitory feedback mechanisms, some of
      which inhibit IL-1 and TNF. A major challenge to sleep research is to define how
      and where these molecular steps produce sleep.

PMID- 9917877
TI  - Brown adipose tissue. More than an effector of thermogenesis?
AB  - Brown adipose tissue (BAT) produces heat by oxidation of fatty acids. This takes
      place when the tissue is stimulated by norepinephrine; the molecular background
      for the ability of BAT to produce heat is the tissue-specific mitochondrial
      protein UCP1. In the classic view of BAT with respect to fever, BAT is an
      effector organ, producing heat especially during the onset phase of the fever.
      There is good evidence that BAT thermogenesis is stimulated via a
      lipopolysaccharide (LPS), interleukin (IL)-1 beta, IL-6, prostaglandin E cascade.
      Under physiologic conditions of constantly stimulated activity, BAT is expected
      to be recruited, but in fevers this is only evident in thyroxine fever. However,
      BAT may be more than merely an effector. There are indications of a correlation
      between the amount of BAT and the intensity of fevers, and brown adipocytes can
      indeed produce IL-1 alpha and IL-6. Furthermore, brown adipocytes are directly
      sensitive to LPS; this LPS sensitivity is augmented in brown adipocytes from IL-1
      beta-deficient mice. Thus, BAT may also have a controlling role in
      thermoregulation. The existence of transgenic mice with ablations of proteins
      central in fever and in BAT thermogenesis opens up possibilities for
      identification and elucidation of this putative new role for brown adipose tissue
      as an endocrine organ involved in the control of fever.

PMID- 9917876
TI  - Cytokine-induced anorexia. Behavioral, cellular, and molecular mechanisms.
AB  - Cytokines induce anorexia. Recent issues concerning mechanistic aspects are: (1)
      Cytokines induce anorexia through different modes of behavioral action, that is,
      by affecting meal size, meal duration, and meal frequency differentially.
      Profiles also depend on the concentration or dosage. (2) The interface between
      the periphery and brain. Specific cytokines may be transported from the periphery
      to the brain. Cytokines generate mediators that can act on peripheral and/or
      brain target sites. Cerebrovasculature endothelium can also generate signals to
      modulate neural activities. Evidence indicates that the proposed vagal afferent
      signaling requires reassessment. Because of paracrine and autocrine actions,
      local cytokine production within the brain can induce anorexia. (3) Cytokines act
      directly on hypothalamic neurons proposed to participate in feeding. (4)
      Cytokine<-->cytokine and cytokine<-->peptide/neurotransmitter interactions are
      critical; for example, cytokines interact to induce anorexia synergistically,
      neuropeptide Y<-->cytokine interactions are antagonist, and cytokine<-
      >neurotransmitter and cytokine<-->leptin<-->neuropeptide Y<-->CRH-glucocorticoid
      and other endocrine interactions are important. A leptin receptor is related to
      gp 130, a signal transducer among interleukin (IL)-6 subfamily receptors; gp 130
      and related molecules may be an interface for feeding control in health and
      disease. Various cytokines upregulate leptin and gp 130. An integrative approach
      combining computerized meal pattern analyses with cellular and molecular
      approaches is being used to characterize mechanisms (ligands, receptors,
      transducing molecules, and intracellular mediators) involved in cytokine-induced
      anorexia.

PMID- 9917878
TI  - Heat tolerance. A role for fever?

PMID- 9917879
TI  - Heat shock proteins and the inflammatory response.
AB  - The heat shock proteins (HSPs) are important in the cellular response to stress
      and in cellular homeostatic functions such as protein synthesis and protein
      transport across membranes. An emerging body of data supports a role for HSPs in
      the inflammatory response, suggesting that HSPs participate in cytokine signal
      transduction and in the control of cytokine gene expression, that HSPs enhance
      antigen presentation to T lymphocytes, and that HSPs displayed on the surface of
      cells are important in targeting cytotoxic cells. Because changes in HSP
      accumulation occur in the whole organism under physiologic conditions,
      understanding the role of HSPs in the immune/inflammatory response may aid in
      understanding the organism's response to danger.

PMID- 9917880
TI  - Benefits and risks of antipyretic therapy.
AB  - Physicians have used various forms of antipyretic therapy since antiquity to
      lower the temperature of febrile patients. Nevertheless, it has yet to be
      determined whether the benefits of antipyretic therapy outweigh its risks. It is
      not known, for example, if core temperatures encountered during the febrile state
      ever reach levels that are intrinsically noxious (and therefore merit antipyretic
      intervention) or when, if ever, fever's metabolic costs exceed its physiologic
      benefits, or if the benefits of symptomatic relief afforded by antipyretic drugs
      consistently exceed their toxicologic cost. Whereas preliminary experimental and
      clinical observations suggest that antipyretic therapy has the potential to
      increase the duration and/or severity of certain infections, such data are as yet
      too fragmentary to draw firm conclusions regarding their validity. Finally,
      although clinicians have long suspected that bacteremia and other severe
      infections might induce fevers that are less responsive to antipyretic therapy
      than are those associated with self-limited infections, this concept has not held
      up under scientific scrutiny. Thus, despite over 2.5 millennia of clinical
      experience, important questions regarding the risks and benefits of antipyretic
      therapy remain to be answered.

PMID- 9917881
TI  - Role of fever in disease.
AB  - Infection, trauma, and injury result in a stereotypical response that includes
      loss of food appetite, increased sleepiness, muscle aches, and fever. For
      thousands of years fever was considered a protective response, and fevers were
      induced by physicians to combat certain infections. But with the advent of
      antipyretic drugs, physicians started to reduce fevers, and fever therapy was
      virtually abandoned. As a result of (1) studies on the evolution of fever, (2)
      further understanding of just how tightly the process of fever is regulated, and
      (3) detailed studies on how fever affects host morbidity and mortality, the view
      of fever as a host defense response has reemerged. However, data indicate that
      not all fevers are protective and that high fevers are maladaptive. These issues
      are discussed in the context of the evolution of host defense responses versus
      modern medical technology. In short, we speculate that patients who would not
      have survived severe sepsis in the past are now being kept alive and that the
      occasionally high fevers seen in these patients may be maladaptive.

PMID- 9917882
TI  - Adaptive interactions between cytokines and the hypothalamic-pituitary-gonadal
      axis.
AB  - Circulating and tissue concentrations of pyrogenic cytokines, especially
      interleukin (IL)-1 beta, vary temporally through the menstrual cycle and
      pregnancy. The secretion of these cytokines in vitro by isolated human
      mononuclear cells is significantly influenced by exogenous gonadal steroids and
      gonadotropins. Reciprocally, cytokines influence gonadotropin secretion by the
      pituitary and steroidogenesis by the ovaries and testes. Several hypotheses have
      been advanced regarding the adaptive value of these interrelationships. Cytokine
      induced synthesis of proteolytic enzymes and extracellular matrix proteins may be
      important for the tissue remodeling necessary for ovulation, implantation, and
      delivery. Tolerance of the fetal allograft may require downregulation of
      cytotoxic effector cells and reciprocal upregulation of humoral and nonspecific
      host defenses. The inhibitory influence of IL-1 beta on the luteinizing hormone
      surge may prevent inopportune conception, and the abortive influences of tumor
      necrosis factor-alpha and gamma interferon may terminate pregnancy during periods
      of infection.

PMID- 9917883
TI  - Proinflammatory cytokines and treatment of disease.
AB  - Bacterial infections in the immunocompromised host cause considerable mortality,
      and even recently developed antimicrobial strategies often fail to cure these
      infections, especially in granulocytopenic patients. Cytokines and hematopoietic
      growth factors have been shown to stimulate host defense mechanisms in vitro and
      in vivo. The possible role of the proinflammatory cytokines interleukin (IL)-1,
      tumor necrosis factor-alpha, IL-6, and IL-8 as modulators of host resistance to
      bacterial infections is discussed. Interleukin-1 has been effective in various
      animal models of potentially lethal bacterial infection, even during severe
      granulocytopenia. The protective mechanism of IL-1 may be mediated by
      downregulation of cytokine receptors and cytokine production and induction of
      acute phase proteins. Moreover, in subacute and chronic infections IL-1
      interferes with microbial outgrowth via mechanisms that have only been partly
      elucidated.

PMID- 9917884
TI  - Relationship between interleukin-1 and interleukin-1 receptor antagonist during
      the development of fever in the rat.

PMID- 9917885
TI  - Effect of galactosamine, an inhibitor of hepatic protein synthesis, on endotoxin
      induced fever and pyrogenic tolerance.

PMID- 9917886
TI  - Cytokine interaction with the menstrual cycle during cold stress and exercise.

PMID- 9917887
TI  - Anterior hypothalamic interleukin-1 receptors are involved in mediation of fever
      during bacterial sepsis in rats.

PMID- 9917888
TI  - Effect of mu-selective opioid antagonists on MIP-1 beta and IL-1 beta-induced
      fever.

PMID- 9917889
TI  - Proinflammatory cytokines in the adverse systemic and neurologic effects
      associated with parenteral injection of a whole cell pertussis vaccine.

PMID- 9917890
TI  - Electron microscopic evidence for induction of cyclooxygenase-2 in brain
      endothelial cells.

PMID- 9917891
TI  - Morphine suppresses development of fever to lipopolysaccharide in rats.

PMID- 9917892
TI  - Desflurane anesthesia inhibits fever in humans.

PMID- 9917893
TI  - Febrile response induced by platelet-derived growth factor (PDGF) in rats.

PMID- 9917894
TI  - Bilateral lesion of hypothalamic paraventricular nucleus abolishes fever induced
      by endotoxin and bradykinin in rats.

PMID- 9917895
TI  - Vagus nerve in fever. Recent developments.

PMID- 9917896
TI  - Interleukin-6 and tumor necrosis factor-alpha during fever induced by bacterial
      infection.

PMID- 9917897
TI  - Explosive increase in Na+ entry to acidified cells at elevated temperature.
      Evidence for the energy depletion model of heat stroke?

PMID- 9917898
TI  - Minimally invasive coronary artery bypass surgery: state of the art.

PMID- 9917899
TI  - Repair of ventricular aneurysm.

PMID- 9917900
TI  - Repair of truncus arteriosus.

PMID- 9917901
TI  - Neurologic injury during coronary revascularization: etiology and management.

PMID- 9917902
TI  - Retrograde cardioplegia.

PMID- 9917903
TI  - Transmyocardial laser revascularization.

PMID- 9917904
TI  - Advances in immunosuppression for heart transplantation.

PMID- 9917905
TI  - Management of small aortic roots.

PMID- 9917906
TI  - Coronary endarterectomy: surgical techniques for patients with extensive distal
      atherosclerotic coronary disease.

PMID- 9917907
TI  - Genetically engineered organs.

PMID- 9917908
TI  - Hypertrophic obstructive cardiomyopathy.

PMID- 9917909
TI  - Traumatic rupture of the thoracic aorta.

PMID- 9917910
TI  - Alpha beta/gamma delta lineage commitment in the thymus of normal and genetically
      manipulated mice.

PMID- 9917911
TI  - Immunoregulatory functions of gamma delta T cells.

PMID- 9917912
TI  - STATs as mediators of cytokine-induced responses.

PMID- 9917913
TI  - CD95(APO-1/Fas)-mediated apoptosis: live and let die.

PMID- 9917914
TI  - A CXC chemokine SDF-1/PBSF: a ligand for a HIV coreceptor, CXCR4.

PMID- 9917915
TI  - T lymphocyte tolerance: from thymic deletion to peripheral control mechanisms.

PMID- 9917916
TI  - Confrontation between intracellular bacteria and the immune system.

PMID- 9917917
TI  - General classes and functions of four-helix bundle cytokines.

PMID- 9917918
TI  - Structural basis for cytokine hormone-receptor recognition and receptor
      activation.

PMID- 9917919
TI  - General mechanisms of cytokine receptor signaling.

PMID- 9917920
TI  - Cytokines in hematopoiesis: specificity and redundancy in receptor function.

PMID- 9917921
TI  - Cytokines in endocrine function.

PMID- 9917922
TI  - Cytokines in brain development and function.

PMID- 9917923
TI  - Thoracoscopic lung biopsy or open lung biopsy for interstitial lung disease.
AB  - Both traditional open lung biopsy through a limited thoracotomy and VATS lung
      biopsy are effective methods for obtaining parenchymal samples in patients who
      have respiratory insufficiency and radiographic pulmonary infiltrates. For
      patients with slowly progressive disease processes, who require an elective
      biopsy, VATS biopsy is the procedure of choice because of the ability to
      visualize and sample multiple areas of the lung, and because of the decreased
      postoperative pain. On the other hand, when patients are critically ill and
      already on high-level ventilatory support, the VATS method offers no advantages
      over the standard minimal thoracotomy.

PMID- 9917924
TI  - Video-assisted thoracic surgery for diagnosis of the solitary lung nodule.
AB  - The finding of a solitary pulmonary nodule is a frequent clinical problem. This
      article outlines the current recommendation for diagnostic management. Video
      assisted thoracic surgery (VATS) has emerged as an excellent diagnostic tool that
      can reduce the incidence of thoracotomy for benign nodules while allowing
      expeditious treatment of early malignancies. The surgical techniques of VATS are
      discussed.

PMID- 9917925
TI  - The current status of video-assisted thoracic surgery lobectomy.
AB  - Video-assisted thoracic surgery (VATS) lobectomy appears to be a safe procedure
      that may have advantages over lobectomy by thoracotomy for selected patients. The
      published series of VATS lobectomies for lung cancer suggest that lobectomy by
      VATS offers survival comparable to that of lobectomy by thoracotomy. VATS
      lobectomy is associated with a low morbidity and mortality and, perhaps, a
      shorter length of stay than thoracotomy. VATS lobectomy is a reasonable treatment
      option for selected patients with Stage I lung cancer when it is performed by
      surgeons with the skills to perform a complete cancer operation via VATS.

PMID- 9917926
TI  - Video-assisted thoracic surgery for lung volume reduction surgery.
AB  - Lung volume reduction surgery by video thoracoscopy can result in significant
      improvement in quality of life and pulmonary function for selected patients
      suffering from severe emphysema. Clinical trials comparing the use of lasers
      versus staples, unilateral versus bilateral procedures, and video surgery versus
      mediansternotomy are summarized. Patient selection and patient care issues are
      addressed. Information gathered from the selection, evaluation, and study of
      almost 500 patients treated surgically for emphysema at a single institution is
      summarized.

PMID- 9917927
TI  - Video-assisted thoracic surgery thymectomy for myasthenia gravis.
AB  - Video-assisted thoracic surgery thymectomy was employed in the management of
      myasthenia gravis in a series of 20 patients. As the technique evolved, the
      authors preferred a right-sided approach, and the technical details of the
      process are discussed. At a mean follow-up of 30 months, clinical results are
      comparable to published series of other approaches. It is hoped that the superior
      cosmesis associated with this less-invasive approach leads to earlier thymectomy
      in management of this disease.

PMID- 9917928
TI  - Video-assisted thoracic surgery pericardial resection for effusive disease.
AB  - In patients who can tolerate single-lung ventilation and who have a long life
      expectancy, VATS offers definitive and durable treatment without the morbidity of
      an open thoracotomy. The patients who may benefit most from this technique
      include those with benign effusive disease, patients with malignant pericardial
      effusions with a good prognosis, and patients with concurrent pulmonary
      pathology.

PMID- 9917929
TI  - The role of video-assisted thoracic surgery in esophageal disease.
AB  - Numerous applications of video-assisted thoracic surgery (VATS) in the management
      of diseases of the esophagus for structural, functional, benign, and malignant
      conditions have been reported. Indications and techniques for the use of VATS in
      the assessment and treatment of esophageal disease are discussed in this article.
      The need for careful evaluation of the safety, efficacy, and cost-effectiveness
      of these techniques is emphasized.

PMID- 9917930
TI  - Minimally invasive cardiac surgery.
AB  - In a short period of time, tremendous progress has been made in the field of
      minimally invasive cardiac surgery. The goal of true "minimally invasive" cardiac
      surgery should be a totally thoracoscopic or transvascular procedure that allows
      a very short hospital stay and prompt patient recovery at acceptable costs. To
      accomplish this goal, efforts to miniaturize and refine
      instrumentation/cannulae/visualization and the development of innovative new
      techniques must be pursued. The concept of performing intracardiac repair of a
      variety of pathologies on the beating heart is under investigation and will
      require a new generation of technology, which will include through-blood imaging,
      such as blood displacement videoscopes, and task-specific instruments. Robotics
      may offer additional assistance in the performance of complex and fine maneuvers.

PMID- 9917932
TI  - Complications after video-assisted thoracic surgery.
AB  - Video-assisted thoracic surgery (VATS) procedures have been adopted widely and
      rapidly for the treatment of a wide range of benign and malignant thoracic
      disorders. To date, there is only incomplete information available about the
      complications associated with these techniques. In this article, the available
      literature addressing the types and incidence of postoperative complications
      associated with VATS procedures is reviewed, as are the problems of incisional
      pain, alterations in respiratory function, and dissemination of malignancy
      following manipulation of tumors by VATS techniques.

PMID- 9917931
TI  - Effect of minimally invasive thoracic surgical approaches on acute and chronic
      postoperative pain.
AB  - Acute postthoracotomy pain and chronic postthoracotomy pain are significant
      problems leading to increased length of hospital stay and medical costs,
      reduction in patient quality of life and patient productivity, and potential
      immunologic derangement that may compromise oncologic surgical results. Minimally
      invasive surgical approaches can potentially benefit the patient by reducing
      postoperative pain-related morbidity. Objective data supporting our inclination
      that these VATS approaches are superior to open thoracic surgical techniques is
      accumulating. Further study of the relative costs, risks, and benefits of
      standard postoperative analgesic management (e.g., epidural analgesia) combined
      with limited thoracotomy compared to VATS techniques is warranted as we try to
      define the most effective perioperative management of the patient requiring
      pulmonary resection.

PMID- 9917933
TI  - Video-assisted thoracoscopy for pleural disease.
AB  - Thoracoscopy has been a valuable modality for the diagnosis and treatment of
      pleural-based disease for almost 100 years. With the development of video
      technology and improved instrumentation, video-assisted thoracoscopy is the
      procedure of choice for effusions of unknown origin, pleural mass biopsy, and
      free-flowing empyema drainage when conventional techniques fail. Reported success
      rates have been very good for diagnosis and treatment of both benign and
      malignant disease, and the morbidity is low.

PMID- 9917934
TI  - Technology acquisition and credentialing controversies.
AB  - In the age of the health care financial squeeze, staying on the cutting edge of
      medical technology is problematic at best. Surgeons must be proactive to design,
      specify, and acquire highly sophisticated, functional thoracoscopic technology.
      Credentialing is a legal process designed to improve patient care quality and
      must be fair and applied to all. An area of contention is credentialing for newly
      designed procedures. Valid reasons for decredentialing, always a difficult issue,
      include personal temporary or permanent medical conditions, patient care quality
      issues, insufficient caseload to maintain proficiency, and personal or
      interpersonal relationship problems.

PMID- 9917935
TI  - The etiology of premature rupture of the membranes.
AB  - The etiology of PROM is multifactorial. It is clear that maternal enzymes,
      maturational and mechanical forces, chorionicamniotic membrane phospholipid
      content, collagen disruption, amniotic cell cytokines induced by fetal signals,
      and bacterial phospholipases and collagenases all play major and interrelated
      roles. It is also clear that the production of oxytocic prostaglandins is a
      major, if not exclusive, common pathway leading to PROM and preterm delivery. The
      increasing awareness of the fetal role, i.e., fetal interleukins, fetal
      polymorphonuclear leukocytes and type V collagenase, make this area of research
      ripe for further investigation. The complex host defense mechanisms and biologic
      variability make any universal treatment impossible. Even with a specific
      etiology determined, the reduced availability of pharmacologic interventions for
      the fetal compartment portend suboptimal success. Therefore, it appears that
      continued research and aggressive measures to optimize the quality and
      availability of prenatal care are the best foci of our efforts.

PMID- 9917937
TI  - Neonatal consequences of preterm PROM.
AB  - Preterm premature rupture of the fetal membranes is associated with 30-40% of
      premature births and is an important cause of perinatal morbidity and mortality.
      Although the major causes of neonatal death associated with PPROM include
      prematurity complications, infection, and pulmonary hypoplasia, rupture in a
      preterm gestation also is associated with an increase in morbidity, including
      cerebral palsy, other developmental delays, as well as chronic lung disease. When
      PPROM occurs, antibiotic prophylaxis has been shown to reduce the potential for
      complications and should be considered. Neonates treated intrapartum with
      antibiotics should have fewer complications, a longer latency period, and an
      improved long-term outlook compared with those without antepartum or intrapartum
      prophylaxis.

PMID- 9917936
TI  - Complications of prolonged PROM and oligohydramnios.

PMID- 9917938
TI  - Antenatal corticosteroids in preterm premature rupture of membranes.
AB  - It is clear that there is no unequivocal indication for the use of antenatal
      corticosteroids in the preterm gestation with PROM. Extrapolating the effects
      seen in gestations with intact membranes, however, there are potential benefits
      in reduction of neonatal respiratory disease and intracranial hemorrhage at the
      expense of increased risks of maternal postpartum infection. Because the lifetime
      harm from the neonatal grave and the sequelae of infection in the mother are
      usually mild, we recommend that antenatal corticosteroids be administered to
      patients with PPROM between the gestational ages of 24-33 weeks in the absence of
      frank maternal or fetal infection or fetal compromise. With the increasing
      acceptance of antenatal corticosteroid therapy, it is unlikely that any further
      prospective randomized trials will be possible because withholding
      corticosteroids may expose patients to unacceptable potential harm. Therefore,
      clinical judgments may have to made based solely on the limited data presently
      available. Hopefully, future clinical investigations will provide useful
      information about the relation between antenatal corticosteroids and perinatal
      infections of the mother and infant in the setting of prophylactic antibiotic
      exposure. Additionally, there is also a need for information establishing a
      clinical profile for the patient with PPROM that accurately predicts when she is
      likely to enter spontaneous labor, thus allowing clinicians to increase the
      likelihood of appropriately administering corticosteroids within 1 week of
      delivery to maximize potential neonatal benefit.

PMID- 9917939
TI  - Tocolytic therapy in preterm PROM.
AB  - Preterm premature rupture of the membranes nearly always leads to preterm labor
      and delivery. Preterm delivery accounts for most of the morbidity attributable to
      PPROM. Antibiotic and corticosteroid treatment may modify the outcome of
      pregnancy after PPROM. The extent of morbidities attributable to PPROM also
      justifies consideration of the use of tocolysis, at least for a limited period of
      time (48 hours) after preterm amniorrhexis. When begun after the onset of
      contractions following PPROM, tocolysis generally does not prolong the latency
      period, although some prolongation may occur before 28 weeks gestational age.
      Prophylactic tocolysis begun before the onset of labor increases the likelihood
      of delaying the onset of labor for 1-2 days, but not beyond. Aggressive long-term
      tocolysis may increase the maternal risk of chorioamnionitis and endometritis.
      None of the reviewed randomized studies demonstrated a significant neonatal risk.
      None of these studies showed an improvement in neonatal outcome, although they
      have not tested the combination of tocolysis and corticosteroid use with
      appropriate controls. The hypothesis that PROM remote from term should be managed
      with 1-2 days of prophylactic tocolysis and corticosteroids to enhance fetal
      pulmonary maturity is attractive, yet it remains inadequately evaluated.

PMID- 9917940
TI  - The diagnosis of intrauterine infection in women with preterm premature rupture
      of the membranes (PPROM).

PMID- 9917941
TI  - Antibiotic therapy in preterm premature rupture of membranes.
AB  - Good quality evidence supports the use of antibiotic therapy in women with
      preterm PROM for whom expectant management is planned. The best evidence supports
      the choice of an extended-spectrum agent or combination administered
      intravenously for 2 days followed by an extended spectrum or combination of oral
      agents for several more days. Despite the effectiveness of antimicrobial therapy
      in this setting, the potential risks of systemic antibiotic administration, such
      as allergic reactions, overgrowth of commensal organisms, and emergence of
      resistant pathogens, much always be kept in mind. Nevertheless, in the majority
      of cases, assuming the patient is a good candidate for expectant management, the
      benefits of antibiotic therapy outweigh the risks.

PMID- 9917942
TI  - Management of preterm premature rupture of the membranes.
AB  - In many cases, the management of preterm PROM will be dictated by the presence of
      advanced labor, intrauterine infection, placental abruption, or nonreassuring
      fetal testing. These patients should be delivered expeditiously, with group B
      streptococcus prophylaxis given where possible, and cesarean delivery reserved
      for routine obstetric indications. The stable patient with PPROM and documented
      fetal pulmonary maturity is best treated by early induction. Alternatively, the
      patient with PPROM remote from term can benefit from conservative treatment.
      Adjunctive antibiotic treatment and serial evaluation of maternal and fetal well
      being offer significant potential for the reduction of perinatal morbidity.
      Although corticosteroid and tocolytic administration remain controversial, there
      is a theoretical benefit to their administration, particularly if concurrent
      antibiotic treatment is given to treat subclinical intrauterine infection.

PMID- 9917943
TI  - Premature rupture of the membranes in term patients: induction of labor versus
      expectant management.

PMID- 9917944
TI  - The perimenopause.

PMID- 9917945
TI  - Oocyte loss and the perimenopause.

PMID- 9917946
TI  - Endocrine changes of the perimenopause.
AB  - Reproductive aging in women is closely tied to the loss of ovarian follicles
      through atresia. The sentinel endocrinologic finding is the monotropic FSH rise,
      associated with a decline in ovarian inhibin B secretion. Fertility becomes
      significantly compromised long before overt clinical signs occur, such as cycle
      irregularity. Compromised fertility is primarily related to oocyte dysfunction.
      As women with regular cycles near the end of the reproductive years, the
      following changes are usually manifested: 1) the selection and development of a
      dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a
      short follicular phase and total cycle length; and 4) ovarian steroid secretion
      is normal. The relationships, if any, between the monotropic FSH rise,
      accelerated follicular atresia, shortened follicular phase, and oocyte quality
      remain to be determined. The next phase of reproductive aging is the
      perimenopause. Lack of predictability is the rule with regard to the nature and
      duration of the perimenopause. Long cycles are interspersed with short ones, and
      intermittent ovulatory cycles are intermingled with periods that are hormonally
      indistinct from the postmenopausal state. Even after the last menstrual period,
      evidence of intermittent ovarian estradiol production may still be detected.
      Although fertility is severely compromised during the perimenopause, ovulation
      may occur without warning and contraception must be practiced if pregnancy is not
      desired. Further studies are needed to elucidate the factors contributing to
      oocyte abnormalities in women of advanced reproductive age, as well as the
      factors that determine the rate of follicle atresia and the length of the
      reproductive life span.

PMID- 9917947
TI  - The symptoms of perimenopause.

PMID- 9917948
TI  - Bleeding problems and treatment.

PMID- 9917949
TI  - Infertility in the older woman.

PMID- 9917951
TI  - Fertility in perimenopausal women.

PMID- 9917950
TI  - Contraception at age 35 years and older.

PMID- 9917952
TI  - Risk factors: assessment and preventive measures.

PMID- 9917953
TI  - Is estrogen replacement indicated in perimenopausal women?

PMID- 9917954
TI  - Radiologic manifestations of the systemic autoimmune diseases.
AB  - Advances in thoracic imaging during the past two decades, such as CT scans and MR
      imaging, have enhanced our understanding of the pleuropulmonary abnormalities
      that develop in the systemic autoimmune diseases. In this article, the thoracic
      radiologic manifestations of several connective tissue diseases (systemic lupus
      erythematosus, rheumatoid arthritis, Sjogren's syndrome,
      polymyositis/dermatomyositis, progressive systemic sclerosis, and anklyosing
      spondylitis), two granulomatous vasculitides, (Wegener's Granulomatosis and Churg
      Strauss syndrome), and antiglomerular basement membrane disease are reviewed.

PMID- 9917955
TI  - Pulmonary pathology in patients with systemic autoimmune diseases.
AB  - The well-recognized pathology of the collagen vascular diseases is reviewed along
      with pathologic findings in systemic vasculitides that commonly involve the lung.
      The pathology of alveolar hemorrhage syndromes is also reviewed.

PMID- 9917956
TI  - Antinuclear antibody testing in systemic autoimmune disease.
AB  - This article discusses the use and interpretation of antinuclear antibody (ANA)
      testing in connective tissue diseases. Methods of ANA detection are discussed and
      analyzed in detail as is the role of ANAs in systemic lupus, scleroderma, and
      polymyositis, connective tissue diseases with prominent pulmonary involvement.

PMID- 9917957
TI  - Antineutrophil cytoplasmic antibodies as markers for systemic autoimmune disease.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) have been associated with systemic
      vasculitis for almost 15 years. Significant advances in our understanding of the
      ANCA phenomenon have occurred with recognition of broadening the spectrum of
      diseases associated with ANCA, identification of specific antigens recognized by
      ANCA, and development of antigen specific assays for clinical use. Nevertheless
      problems continue for the chest physician in interpretation of this test.
      Although antigen specific testing improves overall performance of the test,
      accurate assessment of pretest probability of disease is still important for
      effective use of ANCA testing.

PMID- 9917958
TI  - Pulmonary manifestations of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily
      affects young women. The respiratory system is more commonly involved in SLE than
      in any other collagen vascular disease. SLE may affect virtually all components
      of the respiratory system, including the upper airway, lung parenchyma, pulmonary
      vasculature, pleura, and respiratory muscles. Respiratory system involvement
      ranges from symptomatic to fulminant and life threatening. This article reviews
      the pulmonary manifestations of SLE, including drug-induced SLE.

PMID- 9917959
TI  - Pulmonary manifestations of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common of the classic connective tissue
      diseases. Its manifestations in the chest are varied as the pleura, lung
      parenchyma, airways, and pulmonary vasculature can all be involved. The approach
      to a patient with RA and respiratory complaints, radiographic findings, or
      physiologic abnormalities requires a broad understanding of these manifestations.
      Moreover, the potential for therapy-related toxicity adds further complexity to
      the pulmonary evaluation of these patients.

PMID- 9917960
TI  - Pulmonary manifestations of Sjogren's syndrome.
AB  - Sjogren's syndrome is one of the most common systemic rheumatic diseases.
      Pulmonary disease is prevalent in Sjogren's syndrome; respiratory manifestations
      include chronic cough, obstructive airways disease, pulmonary lymphoma, and
      interstitial lung disease that may progress to severe pulmonary fibrosis.

PMID- 9917961
TI  - The lung in polymyositis.
AB  - Polymyositis is associated with a variety of pulmonary manifestations that may
      complicate an established case, occur simultaneously with the muscle
      manifestations, or precede the muscle disease. Included are respiratory muscle
      involvement, aspiration syndromes, and a variety of interstitial lung reactions.

PMID- 9917962
TI  - Manifestations of scleroderma pulmonary disease.
AB  - Scleroderma is a multisystem disease of unknown cause characterized by synthesis
      and deposition of excessive extracellular matrix and vascular anti-GBM
      antibodies, leading to pulmonary hemorrhage and glomerulonephritis with rapidly
      progressive renal insufficiency. Recent advances in the understanding of disease
      pathogenesis and diagnosis and treatment have significantly improved our ability
      to recognize the syndrome, distinguish it from other similar disorders, and offer
      successful treatment. This article focuses on the pathogenetic features, clinical
      manifestations, diagnostic strategies, and therapeutic principles of anti-GBM
      disease.

PMID- 9917964
TI  - Pulmonary manifestations of ankylosing spondylitis and relapsing polychondritis.
AB  - Ankylosing spondylitis is a chronic inflammatory disease that affects chiefly the
      joints of the axial skeleton. It is a multisystem disease. Several extra
      auricular manifestations of ankylosing spondylitis have been described including
      ocular, cardiovascular, renal, and neurologic complications. Pulmonary
      involvement consists principally of upper lobe fibrocystic changes and chest wall
      restriction. Relapsing polychondritis, on the other hand, is a rare disorder
      characterized by progressive inflammation and degeneration of the cartilaginous
      structures and other connective tissues throughout the body. Involvement of the
      respiratory tract is identified in more than one-half of patients with relapsing
      polychondritis.

PMID- 9917963
TI  - Respiratory complications in mixed connective tissue disease.
AB  - The term mixed connective tissue disease is used to identify the patients with
      combined clinical features of systemic lupus erythematosus, scleroderma or
      progressive systemic sclerosis, and polymyositis-dermatomyositis. A prerequisite
      for the diagnosis of mixed connective tissue disease is the presence, in the
      serum, of high titers of antibodies against uridine-rich RNA-small nuclear
      ribonucleoprotein (snRNP). Respiratory and nonrespiratory features of the disease
      follow those seen in systemic lupus erythematosus, scleroderma, or progressive
      systemic sclerosis, and polymyositis-dermatomyositis. Respiratory involvement is
      observed in 20% to 80% of patients. Major respiratory manifestations and their
      incidences described include interstitial pneumonitis and fibrosis (20% to 65%),
      pleural effusion (50%), pleurisy (20%), and pulmonary hypertension (10% to 45%).
      Other pulmonary features consist of pulmonary vasculitis, pulmonary
      thromboembolism, aspiration pneumonia, pulmonary hemorrhage, pulmonary nodules,
      pulmonary cysts, obstructive airways disease, mediastinal lymphadenopathy,
      pulmonary infections, hypoventilatory respiratory failure, and diaphragmatic
      dysfunction. Pulmonary hypertension is a serious complication; rapid
      deterioration and death have occurred in spite of corticosteroid and cytotoxic
      chemotherapy.

PMID- 9917965
TI  - Pulmonary vasculitis.
AB  - Pulmonary vascular inflammation may be seen in a variety of primary lung diseases
      and in the setting of numerous systemic illnesses. This article reviews those
      entities in which pulmonary vasculitis represents a central feature of the
      pathologic process (Wegener's granulomatosis, Churg-Strauss syndrome, and
      pulmonary capillaritis). In addition, features of pulmonary involvement in other
      systemic vasculitides (Giant Cell Arteritis, Takayasu's Arteritis, and Behcet's
      disease) are described. Finally, general principles for the treatment of
      vasculitis are reviewed.

PMID- 9917966
TI  - Pulmonary toxicity of drugs used to treat systemic autoimmune diseases.
AB  - A number of drugs used to treat systemic autoimmune diseases can cause
      respiratory complications. These include bronchospasm, noncardiac pulmonary
      edema, interstitial pneumonitis and fibrosis, hypersensitivity, and numerous
      other disorders. Additionally, some of these drugs increase the risk of
      infections, particularly with opportunistic organisms. This article reviews the
      clinical presentation and mechanism of toxicity of drug related pulmonary
      complications.

PMID- 9917967
TI  - Cardiovascular manifestations of systemic autoimmune diseases.
AB  - The systemic autoimmune diseases are a protean group of illnesses that primarily
      affect the joints, muscles, and connective tissue. All aspects of the
      cardiovascular system can be involved with clinical consequences ranging from
      asymptomatic abnormalities to serious life-threatening conditions. This article
      discusses the cardiovascular manifestations of the systemic autoimmune diseases
      with particular focus on clinical pathophysiology and management.

PMID- 9917968
TI  - Pulmonary manifestations of Goodpasture's syndrome. Antiglomerular basement
      membrane disease and related disorders.
AB  - Goodpasture's syndrome, or antiglomerular basement membrane disease, is a
      disorder in which lungs and kidneys are affected by the binding of anti-GBM
      antibodies, leading to pulmonary hemorrhage and glomerulonephritis with rapidly
      progressive renal insufficiency. Recent advances in the understanding of disease
      pathogenesis and diagnosis and treatment have significantly improved our ability
      to recognize the syndrome, distinguish it from other similar disorders, and offer
      successful treatment. This article focuses on the pathogenetic features, clinical
      manifestations, diagnostic strategies, and therapeutic principles of anti-GBM
      disease.

PMID- 9917969
TI  - The team approach in the management of congenital and acquired deformities.
AB  - This article provides a summary of practices and guidelines for the design and
      methods used to form interdisciplinary medical teams. Education and
      organizational resources are discussed with regard to children with congenital
      anomalies, specifically craniofacial and cleft lip and palate deformities. The
      team format is recommended to maximize efficiencies and assure a continuum of
      care in the evolving managed care environment.

PMID- 9917970
TI  - Algorithms for the treatment of cleft lip and palate.
AB  - Developing standardized outcomes and algorithms of treatment is a constantly
      evolving task. This article examines four variables in this process: cleft type,
      operative technique, surgical experience, and timing. Input from international
      cleft lip and palate programs regarding techniques and treatment modalities
      provide a dynamic tool for assessment and the development of guidelines in the
      treatment of the cleft lip and palate patient.

PMID- 9917971
TI  - The diagnosis and treatment of common birthmarks.
AB  - In the management and evaluation of several of these birthmarks, it is
      advantageous, if not imperative, to apply a multidisciplinary approach. The
      patients benefit most from a cooperative team of physicians, often including the
      pediatrician, dermatologist, plastic surgeon, radiologist, and pathologist.
      Because of the often extensive presentation of many of these lesions, such an
      approach is extremely useful in planning their evaluation and management.

PMID- 9917972
TI  - Brachial plexus birth injuries and current management.
AB  - OBPP is a condition that, for the majority of patients, resolves spontaneously
      with appropriate nonoperative treatment. However, those patients who do not
      improve spontaneously now have a better chance for recovery owing to recent
      advances in microsurgery and nerve-transfer techniques. The most important aspect
      of therapy is timely recognition and referral.

PMID- 9917973
TI  - Congenital hand problems. Terminology, etiology, and management.
AB  - Although simple "cookbook" treatment plans for most congenital hand problems are
      not possible, certain guiding principles should be followed. It is an important
      to identify when to operate as it is to know when not to operate. The timing of
      surgical interventions as well as the sequence of multistaged interventions play
      an important role in ultimate function of the hand. It may not always be possible
      to achieve both satisfactory power grasp and precision handling. Redistributing
      functional patterns that we have generally employed in our approach to traumatic
      injuries can be used in planning therapy for congenital malformations of the hand
      to try to achieve the best possible function with the available functioning
      anatomic parts.

PMID- 9917974
TI  - Applications of distraction osteogenesis. Part I.
AB  - Distraction osteogenesis (DO) of facial bones is a recent development in the
      treatment of pediatric patients. The use of DO in current clinical practice of
      pediatric reconstructive surgery is primarily limited to severe deformities of
      the lower jaw, most of which are congenital in nature. Clinical experience with
      DO for early facial deformities remains limited, and no authoritative works are
      currently available to guide clinicians in the techniques or indications for DO
      of the facial skeleton.

PMID- 9917975
TI  - Applications of distraction osteogenesis. Part II.
AB  - Distraction osteogenesis is helpful for digit lengthening for congenital and post
      traumatic deficits. Distraction lengthening is also helpful for soft tissue
      stretching such as for radial dysplasia. This article reviews some of these uses
      for distraction osteogenesis.

PMID- 9917976
TI  - The Ilizarov method. Orthopedic and soft tissue applications.
AB  - The Ilizarov method has broad applications for the generation of bone and soft
      tissue via an external fixator composed of small pins, tensional wires, rings,
      hinges and distractors. The success of the technique depends on adherence to
      Ilizarov's principles of tension-stress phenomenon: preservation of the tissues'
      blood supply, frequent distraction in small increments, and full function of the
      extremity.

PMID- 9917977
TI  - Surgery of the eyelids.
AB  - This article reviews the most common pediatric oculoplastic conditions and
      addresses clinical evaluation as well as medical and surgical management. The
      complex issues of amblyopia and special considerations for eyelid surgery in
      children are discussed. A step-by-step approach is used in the treatment of many
      common pediatric oculoplastic conditions, including congenital blepharoptosis and
      lid margin defects. Surgical options are explored and clinical examples are
      provided.

PMID- 9917978
TI  - Neuropsychologic impact of facial deformities in children. Neurodevelopmental
      role of the face in communication and bonding.
AB  - The face is the primary tool of human communication. In early childhood, the face
      plays a crucial role in bonding and attachment. Severe craniofacial problems may
      alter bonding and attachment, thereby resulting in future risk for emotional,
      behavioral, and social problems. Clinical and research findings, while
      incomplete, suggest that this is the case. This conceptual understanding of the
      key role of face-to-face communication in early childhood provides a compelling
      rationale for early repair of craniofacial deformations.

PMID- 9917979
TI  - Plastic surgical problems in the neonatal intensive care unit.
AB  - As technology advances, complications related to these technologies present
      plastic surgeons with an array of new and difficult problems to treat. By
      expanding on the general principles of wound healing and applying similar
      advances in wound care and microsurgery, many of these problems can be managed
      effectively, and successful outcomes achieved. Only by remaining actively
      involved in the coordinated, interdisciplinary treatment of these critically ill
      and premature infants will the long-term complications of such injuries be
      minimized.

PMID- 9917980
TI  - Common problems seen by the plastic surgery emergency room service.
AB  - This article covers many issues of particular interest to the care of the child
      who presents to the emergency department with a traumatic wound. General concepts
      regarding the staffing of an emergency department, staff qualifications, and
      their consultation patterns are reviewed. Issues pertaining to the management of
      children in the emergency setting, including an update on outpatient sedation and
      analgesia and some infectious disease considerations are also discussed.

PMID- 9917982
TI  - Essentials of a complete physical examination.
AB  - The goal of the physical examination is to obtain valid information concerning
      the health of the patient. The examiner must be able to identify, analyze, and
      synthesize the accumulated information into a comprehensive assessment. This
      article outlines the details of the examinations of the individual organ systems
      that should be evaluated during a podiatric screening physical examination. Some
      parts of the physical examination have been omitted intentionally. Attention is
      paid to the recognition of pedal manifestations of systemic disease.

PMID- 9917983
TI  - Anxiety, depression, and diseases of the lower extremities.
AB  - There are many physical disorders that have little or no organic basis. Many of
      these conditions are caused by mental pathology. Certain emotional disorders can
      magnify the person's ability to perceive pain. Anxiety and depression are often
      the culprits. It behooves the podiatrist to be aware that anxiety and depression
      can be a cause of foot and ankle pain or that they can exacerbate true physical
      symptoms. The podiatrist should be able to perform a rudimentary psychological
      evaluation in the outpatient clinical setting, and should be prepared to make a
      timely and proper referral to a mental health professional for additional testing
      and treatment.

PMID- 9917984
TI  - Lower extremity manifestations of vascular disease.
AB  - All podiatrists are required to know the anatomy and pathophysiology of vascular
      pathology because it is the leading cause of morbidity and mortality in the
      western world and a frequent complaint of podiatry patients. Podiatrists have a
      unique opportunity to reduce the risk of lower extremity vascular pathology,
      specifically PVD, by encouraging proper diet and exercise in the podiatric
      patient. Because the next century will bring a population explosion of older
      people, particular attention must be paid to the multiple and complex disorders
      that impair functional independence and compromise quality of life--one of the
      most important disorders being vascular disease. Successful treatment depends on
      recognition of lower extremity pathology (whether it be arterial, venous, or
      lymphatic) and the possible suprastructural causes and timely referrals to a
      vascular specialist when indicated.

PMID- 9917985
TI  - Bone and joint manifestations of systemic infectious diseases.
AB  - Bone and joint infections can occur as the consequence of a wide variety of
      systemic diseases. Disseminated fungal and mycobacterial infections, hepatitis,
      syphilis, gonorrhea, Lyme disease, and AIDS can all have osteoarticular
      manifestations. A thorough knowledge of the wide range of potential pathogens is
      key to establishing a correct diagnosis and instituting appropriate treatment.

PMID- 9917986
TI  - Nonsteroidal anti-inflammatories (NSAIDS), oral hypoglycemics, and topical
      steroids. An overview.
AB  - This article reviews the pharmacology, pharmacokinetics, adverse effects, drug
      interactions, and pedal and systemic indications of NSAIDs, oral hypoglycemics,
      and topical steroids. The integral involvement of these drugs in podiatric
      practice is also reviewed.

PMID- 9917987
TI  - Lower extremity manifestations of neuromuscular diseases.
AB  - Neuromuscular disorders must be considered when a patient presents with a pes
      cavus deformity; lower extremity weakness; difficulty in walking; or cramps,
      stiffness, fatigue, pain, or paresthesia in the extremities. In those instances
      in which a neurologic disease is considered, distinctions between central and
      peripheral nervous system origin, focal versus generalized pathology, and static
      versus progressive course are critical in the diagnosis and treatment of the
      disorder. The complexities of the nervous system often result in missed or
      delayed diagnosis of these syndromes. Patients affected with neurologic diseases
      often require diagnostic and therapeutic interventions from various specialists.
      This article presents a systematic approach to the patient with a neurologic
      disorder, with special emphasis on neuromuscular manifestations in the lower
      extremities. Key observations to aid in the recognition of neuromuscular
      dysfunction are presented, along with an approach to diagnostic evaluation and
      management for these patients.

PMID- 9917988
TI  - The foot and systemic disease. Differential diagnoses.
AB  - The discipline of medicine is truly a combination of both science and art, and
      nowhere is this more true than in the practice of differential diagnosis. From
      the initial clinic visit, when the patient presents with a nonspecific symptom,
      until the final treatment is rendered, the clinician must constantly and
      critically evaluate his or her diagnosis. This process can be expedited by using
      a consistent and comprehensive methodology that reminds the clinician to
      entertain the full spectrum of causes. Two such methodologies have been presented
      in this article. It is important, however, to note that the systems presented
      here are by no means the sole, or even best, methods. The clinician should
      experiment and discover what works best for him or her. Any system is ideal if it
      allows the clinician to consistently derive the correct diagnosis in a short
      amount of time. After all, the most important part of any treatment is the proper
      diagnosis.

PMID- 9917989
TI  - Cultures of psychiatry and mental health care in postwar Britain and The
      Netherlands.

PMID- 9917990
TI  - Restructuring mental health services in twentieth century Britain.

PMID- 9917991
TI  - Dutch psychiatry after World War II: an overview.

PMID- 9917992
TI  - Before anti-psychiatry: 'mental health' in wartime Britain.

PMID- 9917993
TI  - Psychiatry and society: the Dutch Mental Hygiene Movement 1924-1960.

PMID- 9917994
TI  - 'They used to call it psychiatry': aspects of the development and impact of
      psychopharmacology.

PMID- 9917995
TI  - LSD and the dualism between medical and social theories of mental illness.

PMID- 9917996
TI  - R. D. Laing in Scotland: facts and fictions of the 'Rumpus Room' and
      interpersonal psychiatry.

PMID- 9917997
TI  - "Messiah of the schizophrenics" Jan Foudraine and anti-psychiatry in Holland.

PMID- 9917998
TI  - The Dennendal experiment, 1969-1974: the legacy of a tolerant educative culture.

PMID- 9917999
TI  - Enemies within: postwar Bethlem and the Maudsley Hospital.

PMID- 9918000
TI  - The changing professional identity of the Dutch psychiatrist 1960-1997.

PMID- 9918001
TI  - From the asylum to the community: the mental patient in postwar Britain.

PMID- 9918002
TI  - The battle against peace-keeping frustrations: psychiatrists and psychologists in
      the Dutch army.

PMID- 9918003
TI  - Anti-psychiatry and the family: taking the long view.

PMID- 9918004
TI  - Raising the anti: Jan Foudraine, Ronald Laing and anti-psychiatry.

PMID- 9918005
TI  - The view from the North Sea.

PMID- 9918006
TI  - Phospholipase A2 and phosphatidylinositol-specific phospholipase C assays by HPLC
      and TLC with fluorescent substrate.

PMID- 9918007
TI  - Fluorometric phospholipase assays based on polymerized liposome substrates.

PMID- 9918008
TI  - Triglyceride lipase assays based on a novel fluorogenic alkyldiacyl glycerol
      substrate.

PMID- 9918009
TI  - Purification and assay of mammalian group I and group IIa secretory phospholipase
      A2.

PMID- 9918010
TI  - Determination of plasmalogen-selective phospholipase A2 activity by radiochemical
      and fluorometric assay procedures.

PMID- 9918011
TI  - Human plasma platelet-activating factor acetylhydrolase.

PMID- 9918012
TI  - Assays for pancreatic triglyceride lipase and colipase.

PMID- 9918013
TI  - Bile salt-activated lipase.

PMID- 9918014
TI  - Determining lipoprotein lipase and hepatic lipase activity using radiolabeled
      substrates.

PMID- 9918015
TI  - Lysosomal acid lipase. Assay and purification.

PMID- 9918016
TI  - Hormone-sensitive lipase and neutral cholesteryl ester lipase.

PMID- 9918017
TI  - Lecithin-cholesterol acyltransferase. Assay of cholesterol esterification and
      phospholipase A2 activities.

PMID- 9918018
TI  - Purification of lipases and phospholipases by heparin-sepharose chromatography.

PMID- 9918019
TI  - Large-scale lipoprotein lipase purification from adipose tissue.

PMID- 9918021
TI  - High-level expression and purification of human hepatic lipase from mammalian
      cells.

PMID- 9918020
TI  - Purification of rat hepatic lipase essentially free of apolipoprotein E and
      apolipoprotein B.

PMID- 9918022
TI  - High-level baculoviral expression of hormone-sensitive lipase.

PMID- 9918023
TI  - High-level baculoviral expression of lysosomal acid lipase.

PMID- 9918024
TI  - One-step purification and biochemical characterization of recombinant pancreatic
      lipases expressed in insect cells.

PMID- 9918025
TI  - Modulation of the expression level of human acidic lipases by various signal
      peptides.

PMID- 9918026
TI  - Immunodetection of lipoprotein lipase: antibody production, immunoprecipitation,
      and western blotting techniques.

PMID- 9918028
TI  - Determining lipase subunit structure by sucrose gradient centrifugation.

PMID- 9918027
TI  - Immunological characterization of digestive lipases.

PMID- 9918029
TI  - Detecting ligands interacting with lipoprotein lipase.

PMID- 9918030
TI  - Monolayer techniques for studying lipase kinetics.

PMID- 9918031
TI  - Efficient immobilization of phospholipase A2.

PMID- 9918032
TI  - An introduction to Internet resources for the molecular and genetic analysis of
      the lipases.

PMID- 9918033
TI  - Techniques for the measurement of lipoprotein lipase messenger RNA.

PMID- 9918034
TI  - In vitro transcription and translation of lipoprotein lipase.

PMID- 9918035
TI  - Induced lipase mutations in the mouse.

PMID- 9918037
TI  - Separation of small-size DNA fragments using agarose gel electrophoresis.

PMID- 9918036
TI  - PCR methodology applied to genetic studies of lipoprotein metabolism and
      atherosclerosis.

PMID- 9918038
TI  - Quantification of mRNA by polymerase chain reaction (PCR) using an internal
      standard and a nonradioactive detection method.

PMID- 9918039
TI  - Generation of transgenic mice.

PMID- 9918041
TI  - Fast ultracentrifugation methods for the separation of plasma lipoproteins.

PMID- 9918042
TI  - Preparative isolation of plasma lipoproteins using fast protein liquid
      chromatography (FPLC).

PMID- 9918040
TI  - Preparation of knockout mice.

PMID- 9918043
TI  - Separation of apolipoproteins by polyacrylamide gel electrophoresis.

PMID- 9918044
TI  - Isolation and purification of serum lipoprotein (a) using lectin affinity.

PMID- 9918045
TI  - Electrophoretic separation of LDL and HDL subclasses.

PMID- 9918046
TI  - Measurement of lipoprotein particles.

PMID- 9918047
TI  - Methodological approaches for assessing lipid and protein oxidation and
      modification in plasma and isolated lipoproteins.

PMID- 9918048
TI  - Separation and quantitation of phospholipid classes by HPLC.

PMID- 9918050
TI  - Determination of the mass concentration and the activity of the plasma
      cholesteryl ester transfer protein (CETP).

PMID- 9918049
TI  - Assays of lecithin cholesterol acyltransferase (LCAT).

PMID- 9918051
TI  - In vitro measurement of lipoprotein and hepatic lipases.

PMID- 9918052
TI  - Cellular assays for lipoprotein receptors.

PMID- 9918053
TI  - Measurements of proteoglycan-lipoprotein interaction by gel mobility shift assay.

PMID- 9918054
TI  - Nutritional status and assessment of patients on home parenteral nutrition:
      anthropometry, bioelectrical impedance, or clinical judgment?
AB  - The optimal method of assessing protein energy nutritional status in patients
      receiving home parenteral nutrition (HPN) is unknown. We evaluated protein energy
      nutritional status in 47 outpatients (23 male; 24 female) on HPN by measuring
      anthropometry, plasma proteins, and lymphocyte counts and compared these with the
      results of subjective clinical assessment and bioelectrical impedance
      measurements. Sixteen of the 47 patients (34%) were underweight (body mass index
      < 5th percentile of the reference) and 21 (45%) were below the 5th percentile of
      the reference for both triceps skinfold thickness and midarm muscle
      circumference. Plasma proteins were subnormal in 1-5 patients (2-11%). Lymphocyte
      counts were subnormal in 19 patients (40%). Clinical assessment classified 23
      patients (49%) as well nourished and 24 (51%) as moderately malnourished.
      Moderately malnourished patients had a significantly lower body mass index than
      well-nourished patients (P = 0.02). Clinical assessment did not correlate with
      bioelectrical impedance analysis. Fat-free mass determined by bioelectrical
      impedance analysis resulted in values up to 9.4 kg lower and 8 kg higher than fat
      free mass obtained by anthropometry. Weighing combined with a subjective clinical
      assessment is sufficient for evaluation of protein calorie nutritional status in
      patients on HPN.

PMID- 9918055
TI  - Benefits of a dietary intervention on weight loss, body composition, and lipid
      profile after renal transplantation.
AB  - The nutritional status of a group of 23 renal transplanted patients with a body
      mass index > 27, hyperlipidemia, and stable renal function were studied before
      and after 6 mo of dietary intervention with the American Heart Association (AHA)
      Step One pattern. The dietary records showed that the intake of total fat
      decreased from 42.2 +/- 5.5 to 33.0 +/- 4.2% (P < 0.001) and the intake of
      saturated fat decreased from 12.8 +/- 1.8 to 9.2 +/- 3.1% (P < 0.01) of total
      calories. The cholesterol intake fell from 352 +/- 10 to 221 +/- 12 mg/d. The
      mean weight loss was 3.2 +/- 2.9 kg (P < 0.001), followed by a significant
      decrease in mean body fat mass (%) measured by triceps skinfold (34.2 +/- 3.3
      versus 32.9 +/- 3.7; P < 0.05), bioelectrical impedance (30.8 +/- 5.7 versus 26.5
      +/- 5.9; P < 0.001), and infrared interactance (37.5 +/- 6.3 versus 34.7 +/- 5.5;
      P < 0.01). After the dietary intervention, lipid profile improved in all
      patients, with a decrease in the mean total cholesterol (237 +/- 32 versus 224 +/
      36 mg/dL; P < 0.05), which was higher in males. Also, low-density lipoprotein
      cholesterol was reduced in male patients (156 +/- 19 versus 136 +/- 11 mg/dL, P <
      0.05), whereas in females low-density lipoprotein cholesterol levels remained
      unaltered. The high-density lipoprotein cholesterol and triacylglycerol values
      were not affected in both males and females by the dietary treatment. The
      reduction in serum cholesterol was inversely correlated with the initial values
      of triceps skinfold (r = 0.52, P < 0.01) and was lower in patients with a body
      mass index > 30 (5.7 versus 2.8%, NS). It is concluded that the obesity and
      hyperlipidemia following renal transplantation may be improved by dietary
      intervention and subsequent weight loss.

PMID- 9918056
TI  - Phenotypic changes in the lipopolysaccharide of Pseudomonas aeruginosa and
      Escherichia coli grown in milk-based enteral nutrition solutions.
AB  - Previous studies have shown enteral nutritional solutions (ENS) contaminated with
      large numbers of microorganisms from the environment or gastrointestinal (GI)
      tract of patients have caused respiratory infections, acute and chronic
      enteritis, and septicemia. The introduction of "closed" enteral feeding systems
      has been used to prevent contaminating organisms from entering enteral feeding
      systems in large numbers. However, there is some discussion as to whether this
      has been an effective measure in reducing ENS-related infections because there is
      anecdotal evidence to suggest that disease processes resulting from enteral
      feeding are still commonplace in the hospital and home. This is because there is
      very little information about the growth of microorganisms in ENS and whether
      growth in ENS may affect the virulence and pathogenicity of microorganisms. This
      study shows that Escherichia coli and Pseudomonas aeruginosa may grow at 25
      degrees C from either high or low initial numbers to up to 9.2 log colony-forming
      units per mL in a range of milk-based ENS. However, these organisms did not grow
      in the fruit-based ENS. The effect on the lipopolysaccharide (LPS) of culturing
      E. coli and P. aeruginosa in milk-based ENS as opposed to standard laboratory
      media was examined using polyacrylamide gel electrophoresis. We found that there
      were significant qualitative changes in the phenotype of O-polysaccharide side
      chains of the LPS from these organisms. O-polysaccharide is known to mediate in
      the complement, antibiotic and bile resistance, and affect adherence. Therefore,
      changes in the virulence and pathogenicity of these microorganisms when cultured
      in ENS may be indicated. Thus, the study provides further evidence for
      reevaluating the microbiologic and immunologic effects of enteral feeding,
      especially on the microbial flora of the GI tract.

PMID- 9918057
TI  - Effect of parenteral and enteral nutrition on hepatic albumin synthesis in rats.
AB  - The route of nutrient delivery may alter the production of albumin and induce
      changes at the molecular level. Donryu rats (n = 75) were divided into the
      following three groups. The oral feeding (OR) group received a non-purified solid
      diet ad libitum, the parenteral nutrition (PN) group received a total parenteral
      nutrition (TPN) solution intravenously, and the enteral nutrition (EN) group
      received intragastric infusions of the TPN solution for 7 d. Serum albumin and
      glucocorticoid levels were measured and messenger RNA (mRNA) levels of albumin
      and hepatic specific transcription factors in the liver were analyzed. Serum
      albumin and albumin mRNA levels in the PN group became significantly decreased
      compared to those in the OR group, whereas the EN group did not show a
      significant difference compared to the OR group. mRNA levels of DBP, D-site
      binding transcription factor for the albumin gene, showed a circadian rhythm in
      the OR and EN groups, but not in the PN group, as indicated by a DBP mRNA level
      at 2200 h in the PN group that was significantly lower than that in the OR group.
      mRNA levels of C/EBP alpha, CCAAT-enhancer binding protein alpha, were highest in
      the OR group and lowest in the PN group. In contrast, mRNA levels of C/EBP beta
      were highest in the PN group and lowest in the OR group. Serum glucocorticoid
      level showed a circadian rhythm in the OR group, highest at 2200 h and lowest at
      1000 h, whereas such a rhythm was not found in either the PN or the EN group.
      Albumin synthesis was down-regulated in PN in association with changes in
      transcription factors. A loss of circadian rhythm reflected in changes of DBP
      mRNA and serum glucocorticoid level may play a role. Down-regulation of albumin
      was improved by enteral feeding, indicating that EN is more advantageous for
      albumin synthesis than PN.

PMID- 9918058
TI  - Effects of glutamine administration on liver regeneration following hepatectomy.
AB  - The intestine is now known to be an important site of protein production in the
      body, and glutamine (GLN) stimulates both secreted and non-secreted protein
      synthesis in the small bowel. The purpose of the present study was to evaluate
      the effect of GLN-supplemented parenteral nutrition on liver regeneration after
      hepatectomy. Animals were divided into two groups: a sham-operated control group
      (Group A) and a 70%-hepatectomy group (Group B). Postoperatively, one-third of
      the animals in each group were maintained on intravenous 10% glucose solution, on
      10% glucose with 2% standard amino acid solution, or 10% glucose supplemented
      with 2% glutamine for 24 h. GLN administration after hepatectomy significantly
      promoted liver regeneration. In addition, assessment of amino acid metabolism
      showed that GLN administration activated GLN metabolism in the intestine and
      promoted alanine uptake by the remnant liver. This metabolic response also
      enhanced both secreted and non-secreted protein synthesis in intestinal
      epithelial cells, especially in cells isolated from the crypts. The proteins
      produced are important as a portal production factor for liver regeneration and
      intestinal cell proliferation. Bacterial and endotoxin translocation, on the
      other hand, was significantly reduced. Thus, the results of this study suggest
      that intravenous administration of GLN after hepatectomy significantly promoted
      liver regeneration.

PMID- 9918059
TI  - Enteral administration of glutamine in purulent peritonitis.
AB  - The intestinal hypomotility associated with purulent peritonitis is generally
      regarded as a contraindication to enteral nutrition. However, enteral nutrition
      may be feasible in suppurative peritonitis if administered with great caution,
      i.e., assuring the appropriate amount, delivery speed, and osmolality of the
      enteral formulation. Glutamine (Gln) increases muscle protein synthesis and
      decreases muscle protein degradation in sepsis, regardless of the route of
      administration. Therefore, administering small amounts of supplemental Gln via
      the enteral route to peritonitis patients may be beneficial. Two purulent
      peritonitis patients received L-Gln through a jejunostomy tube. The average
      amount of supplemental Gln was 16 g/d. Systemic inflammatory responses, i.e.,
      high temperature and a high serum C-reactive protein level, persisted throughout
      the treatment period. Femoral arterial and venous blood samples were drawn
      simultaneously for determination of amino acid levels before and after 7 d of Gln
      supplementation. Enterally administered Gln was well-tolerated by both patients.
      There was an increase in plasma Gln levels after Gln supplementation. Moreover,
      the release of Gln, alanine, and phenylalanine from the lower extremities was
      lower after as compared to before Gln supplementation. Enteral administration of
      Gln may be feasible even in purulent peritonitis.

PMID- 9918060
TI  - Some new developments in the understanding of oropharyngeal and postingestional
      controls of meal size.
AB  - This review focuses on new developments in the understanding of how oropharyngeal
      and postingestional stimulation control the ingestive behavior of the rat
      ingesting liquids. With the development of the computer-controlled lickometer it
      is now possible to measure and analyze in fine detail the impact these two
      variables have on the rat's licking behavior. Because variations in this behavior
      are responsible for variations in intake this methodology is beginning to provide
      a clearer picture of how oropharyngeal and postingestional stimulation control
      ingestive behavior and interact to control meal size. These developments should
      in turn ultimately provide the basis for better understanding of how the motor
      systems of the brain control the behavior that supplies the body with its
      nutrients.

PMID- 9918061
TI  - State of artificial nutrition in Hungary: standpoint and methodologic
      recommendations.

PMID- 9918062
TI  - Structure and metabolic fate of triacylglycerol- and phospholipid-rich particles
      of commercial parenteral fat emulsions.
AB  - The lipid emulsions used in parenteral nutrition are constituted of particles
      rich in triacylglycerols (TAG) called artificial chylomicrons (200-500 nm in
      diameter; monolayer of phospholipids [PL] enveloping a TAG core) and PL-rich
      particles called liposomes (diameter inferior to 80 nm; bilayer of PL around an
      aqueous phase), which represent the excess emulsifier. Introduced into the
      circulation, the two populations of particles come into contact with circulating
      lipoproteins and cell membranes and experience the same overall fate: exchanges
      and transfers of lipids and apolipoproteins, enzymatic hydrolysis of TAG and PL,
      and internalization by different tissues. The relative importance of these
      different metabolic processes varies depending on the type of particle. The
      artificial chylomicrons undergo a hydrolysis of their TAG by lipoprotein lipase,
      with a release of fatty acids and formation of smaller particles of remnants,
      which are rapidly removed by the liver. In delivering fatty acids to the tissue,
      artificial chylomicrons fulfill an energy transport function similar to the
      natural chylomicrons. The liposomes hold little energy interest, and they also
      have deleterious effects when infused in excess. They inhibit the lipolysis of
      artificial chylomicrons and, by actively capturing endogenous cholesterol, they
      stimulate tissue cholesterogenesis and accumulate in the blood as lipoprotein-X,
      a long-lived abnormal lipoprotein. To limit as much as possible the metabolic
      perturbations due to the intravenous administration of exogenous PL, the emulsion
      has to be infused at a low rate, and should contain the minimal amount of excess
      PL.

PMID- 9918063
TI  - Serum prealbumin in institutionalized populations.

PMID- 9918065
TI  - Assessment of nutritional status in patients on home parenteral nutrition.

PMID- 9918066
TI  - Enteral tube feeds as a source of infection: can we reduce the risk?

PMID- 9918067
TI  - Immunonutrition--concluding remarks.

PMID- 9918068
TI  - Comment on development of nutritional support in evolving markets.

PMID- 9918069
TI  - Perioperative nutrition in oncologic patients.

PMID- 9918071
TI  - Endoluminal brushing in catheter-related sepsis: a "sweeping" statement.

PMID- 9918070
TI  - Role of lipids in insulin resistance and type 2 diabetes mellitus development.

PMID- 9918072
TI  - Home parenteral nutrition in acquired immunodeficiency syndrome patients.

PMID- 9918073
TI  - Oxalogenesis in parenteral nutrition mixtures.

PMID- 9918074
TI  - Is glutamine a pretender to the throne?

PMID- 9918075
TI  - Ceruloplasmin and iron: vindication after 30 years.

PMID- 9918076
TI  - Re: Glutamine homologues and derivatives: a limiting factor in current artificial
      nutrition by F.H.R. Pesty, PharmD and F. Sultan, PhD.

PMID- 9918077
TI  - Electrical maturation trajectory of human tissues identified by bioelectrical
      impedance vector analysis.

PMID- 9918078
TI  - Privacy versus progress: the international debate over medical records research.

PMID- 9918079
TI  - Mexico: a challenge for nutrition professionals.

PMID- 9918080
TI  - Anything else to add?

PMID- 9918082
TI  - The degree of masculine differentiation of obesities: a factor determining
      predisposition to diabetes, atherosclerosis, gout, and uric calculous disease.
      1956.

PMID- 9918081
TI  - Workshop on Folate, B12, and Choline. Sponsored by the Panel on Folate and other
      B vitamins of the Standing Committee on the Scientific Evaluation of Dietary
      Reference Intakes, Food and Nutrition Board, Institute of Medicine, Washington,
      D.C., March 3-4, 1997.

PMID- 9918083
TI  - Internet: personal use by obstetric and gynecological sonologists.

PMID- 9918084
TI  - The mid-pregnancy ultrasound assessment--quo vadis?

PMID- 9918085
TI  - Screening for chromosomal abnormalities at 10-14 weeks: the role of ductus
      venosus blood flow.
AB  - OBJECTIVE: To assess the possible role of Doppler ultrasound assessment of ductus
      venosus blood flow in screening for chromosomal abnormalities at 10-14 weeks of
      gestation. METHODS: Ductus venosus flow velocity waveforms were obtained
      immediately before fetal karyotyping in 486 consecutive singleton pregnancies at
      10-14 weeks of gestation. All cases were screened for chromosomal defects by a
      combination of maternal age and fetal nuchal translucency thickness. The peak
      systolic and diastolic velocities, the velocity during atrial contraction and the
      pulsatility index were measured. RESULTS: There were 63 chromosomal defects (38
      cases of trisomy 21, 12 cases of trisomy 18, seven cases of trisomy 13, three
      cases of Turner's syndrome and three cases of triploidy). In 57 (90.5%) cases
      there was reverse or absent flow during atrial contraction. Abnormal ductus
      venosus flow was also observed in 13 (3.1%) of the 423 chromosomally normal
      fetuses. In the chromosomally abnormal group, compared to the normal group, the
      median heights of the S and D waves were significantly lower and the pulsatility
      index was significantly higher. However, multivariate regression analysis
      demonstrated that only the height of the A wave provided a significant
      independent contribution in distinguishing between the chromosomally normal and
      abnormal groups. CONCLUSION: These preliminary results suggest that assessment of
      ductus venous blood flow in pregnancies considered to be at high risk for
      chromosomal defects may result in a major reduction in the need for invasive
      testing, with only a small decrease in sensitivity.

PMID- 9918086
TI  - The significance of choroid plexus cysts, echogenic heart foci and renal
      pyelectasis in the first trimester.
AB  - OBJECTIVE: To determine the significance of certain soft ultrasonographic markers
      for chromosomal abnormalities in the first trimester. DESIGN: This was a
      prospective cross-sectional study. SETTING: University Department of Obstetrics
      and Gynaecology, London, UK. METHODS: A total of 5385 women from an unselected
      population underwent a detailed assessment of fetal anatomy at 11-14 weeks of
      gestation (confirmed by crown-rump length) by transabdominal sonography (5.0 MHz)
      and transvaginal sonography (6.0 MHz) when necessary. RESULTS: In normal fetuses,
      the prevalences of choroid plexus cysts, pyelectasis and echogenic heart foci
      were 2.2, 0.9 and 0.6%, respectively in the first trimester and 2.0, 0.8 and
      0.8%, respectively in the second trimester. Pyelectasis (likelihood ratio = 8.0,
      p = 0.03) and echogenic heart foci (likelihood ratio = 10.3, p = 0.02) were found
      to be associated significantly with fetal aneuploidy, while choroid plexus cysts
      were not. CONCLUSIONS: Although the majority of aneuploidies were detected by
      increased nuchal translucency and/or the presence of structural abnormalities
      (78%; 25/32), the use of soft ultrasonographic markers in the first trimester
      would have increased the overall detection by a further 3%. These data are
      preliminary and many thousands of pregnancies will need to be examined to
      determine the significance of the individual markers in different chromosomal
      abnormalities.

PMID- 9918087
TI  - The significance of choroid plexus cysts in an unselected population: results of
      a multicenter study.
AB  - OBJECTIVES: Choroid plexus cysts are commonly found at the time of a routine
      second-trimester scan, but there is much debate as to their clinical
      significance. The aims of this study were to define the incidence of choroid
      plexus cysts in an unselected population and describe their association with
      aneuploidy. DESIGN: This was a prospective, observational multicenter study.
      SUBJECTS: Subjects were all fetuses found to have choroid plexus cysts with a
      maximum diameter of 3 mm or greater and who were between 14 and 24 weeks'
      gestation when scanned in the routine ultrasound department at any of the 13
      participating hospitals. RESULTS: There were 658 fetuses with choroid plexus
      cysts in a total of 101,600 births. The overall incidence of aneuploidy was 2.1%,
      but in fetuses with isolated choroid plexus cysts the incidence of proven
      aneuploidy was 0.5% (95% confidence interval (CI), 0.1-1.4%). If age is taken
      into consideration, then the incidence of aneuploidy in fetuses with isolated
      choroid plexus cysts where the mother is under the age of 36 years was 0.36% (95%
      CI, 0.04-1.3%), and 2.4% (95% CI, 0.06-12.6%) in older women. CONCLUSIONS: We
      conclude that the presence of choroid plexus cysts increases the risk for
      aneuploidy, mainly trisomy 18. In the majority of cases, the final risk will
      remain small, but will increase as maternal age increases.

PMID- 9918088
TI  - Nuchal translucency audit: a novel image-scoring method.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and
      reproducibility of a novel image-scoring method of first-trimester nuchal
      translucency measurement as an objective tool of ongoing audit and training.
      DESIGN: This was an independent evaluation of nuchal translucency images by three
      separate reviewers unaware of the examiner. SUBJECTS: There were 105 consecutive
      singleton pregnancies undergoing first-trimester screening. METHODS: Each image
      was scored according to the following criteria: section (oblique, 0; mid
      sagittal, 2), caliper placing (misplaced, 0; proper, 2), skin line (nuchal only,
      0; nuchal and back, 2), image size (unsatisfactory, 0; satisfactory, 1), amnion
      (not visualized, 0; visualized, 1) and head position (flexion/hyperextension, 0;
      straight, 1). The final score was categorized into one of four quality groups:
      excellent (8-9), reasonable (4-7), intermediate (2-3), unacceptable (0-1).
      RESULTS: The distributions of the four quality groups were similar between the
      three reviewers: 11.4% were classified as excellent, 57.1% as reasonable, 25.7%
      as intermediate and 5.7% as unacceptable. Inter-reviewer agreement showed
      identical classification, by each pair of reviewers, from 65.7% to 74.3%, and
      partial agreement to neighboring quality groups from 25.7% to 34.3% of the cases.
      In none of the cases did the reviewers differ in categorizing cases to remarkably
      different quality groups. Application of the auditing method to the examiners
      showed similar distribution to the various quality groups and similar mean final
      score of 4.69 (0.39, SE), 4.54 (0.15, SE) and 4.65 (0.15, SE). CONCLUSIONS: The
      described image-scoring method represents a new approach towards the evaluation
      of ultrasound performance as a whole and nuchal translucency measurement in
      particular. It may be employed by every center in an independent manner with
      minimal resources and regardless of the method of risk assessment. More studies
      will be needed to determine the standards required from the examiners and to
      elucidate the contribution of the proposed auditing method to the examination's
      quality and the process of training.

PMID- 9918089
TI  - Fetal cardiac measurements derived by transvaginal and transabdominal cross
      sectional echocardiography from 14 weeks of gestation to term.
AB  - OBJECTIVE: Most of the routine ultrasound screening in our institution consists
      of early transvaginal examinations at 14-17 weeks. Complete fetal
      echocardiography is performed in every case. However, normal values for most
      fetal cardiac structures at this stage of gestation are not available. Our aim
      was to construct normal ranges for fetal cardiac structures, derived from cross
      sectional echocardiography, at 14-40 weeks of gestation. DESIGN: A prospective
      study was performed. The study group consisted of 637 pregnant women referred for
      a routine sonographic examination. Women with abnormal prenatal or postnatal
      outcome were not included in the study. Transvaginal examinations were used for
      14-17 weeks of gestation. More advanced pregnancies were examined
      transabdominally. RESULTS: We constructed normal ranges for the left and right
      end-diastolic transverse ventricular diameters (n = 637), left/right ventricular
      ratio (n = 637), aortic root diameter (n = 637), pulmonary artery diameter (n =
      637), aortic/pulmonary ratio (n = 490), left and right transverse atrial
      diameters (n = 201) and left/right atrial ratio (n = 201). CONCLUSIONS: The
      results provide the examiner with normal ranges for fetal cardiac structures for
      the early transvaginal examination. The continuity of all curves from 14 to 40
      weeks of gestation allows follow-up of any specific fetus to term.

PMID- 9918090
TI  - Ultrasound measurement of the fetal cavum septi pellucidi.
AB  - OBJECTIVES: To establish normative data for the width of the fetal cavum septi
      pellucidi at various gestational ages. SUBJECTS AND METHODS: A total of 608
      consecutive fetuses between 19 and 42 gestational weeks were included in this
      prospective study. The largest width of the cavum septi pellucidi was measured by
      two-dimensional ultrasound. Piecewise regression analysis was used to study the
      relationships between the width of the fetal cavum septi pellucidi, gestational
      age and biparietal diameter. RESULTS: The fetal cavum septi pellucidi width
      increased gradually between 19 and 27 weeks of gestation and then plateaued
      between 28 weeks and term. Regression analysis revealed significant associations
      between cavum septi pellucidi width and gestational age, and cavum septi
      pellucidi width and biparietal diameter. CONCLUSIONS: The present study provides
      normative data for fetal cavum septi pellucidi width and useful information about
      the development of the midline brain structure in the fetus.

PMID- 9918091
TI  - Transvaginal ultrasonography at 18-23 weeks in predicting placenta previa at
      delivery.
AB  - OBJECTIVE: To evaluate whether transvaginal ultrasonography at 18-23 weeks'
      gestation is useful in predicting placenta previa at delivery. DESIGN: We
      performed transvaginal ultrasonography in addition to routine transabdominal
      ultrasonography in 3696 consecutive non-selected pregnant women with singleton
      fetuses and measured the distance from the placental edge to the internal
      cervical os. RESULTS: In 57 of 3696 patients (1.5%), the placental edge extended
      to or over the internal cervical os. In 27 patients (0.7%), the placenta extended
      > or = 15 mm over the internal cervical os; in these cases the positive
      predictive value of placenta previa at delivery was 19% (95% CI, 6-38%) with 100%
      (95% CI, 48-100%) sensitivity. With > or = 25 mm used as the cut-off point, ten
      cases (0.3%) were screen-positive and the positive predictive value for previa at
      delivery was 40% (95% CI, 12-74%) and sensitivity was 80% (95% CI, 28-100%). The
      frequency of placenta previa at delivery in this population was five of 3696
      (0.14%, 95% CI, 0.04-0.31%). CONCLUSIONS: We recommend confirmatory transvaginal
      ultrasonography if placenta previa is suspected at transabdominal ultrasonography
      in mid-pregnancy, and reexamination at 26-30 weeks if the placental edge covers
      the internal cervical os by 15 mm or more.

PMID- 9918092
TI  - Antenatal diagnosis of velamentous umbilical cord insertion and vasa previa with
      color Doppler imaging.
AB  - OBJECTIVE: To determine whether cord insertion can be consistently visualized and
      whether velamentous cord insertion and vasa previa can be consistently identified
      with color Doppler imaging during routine sonography in the mid-trimester.
      DESIGN: A prospective study. SUBJECTS: A total of 587 fetuses at 18-20 weeks'
      gestation. METHODS: During routine ultrasound examinations, the sonographer was
      instructed to take additional time and to image the placental cord insertion with
      color Doppler imaging and classify this as normal, velamentous or 'not seen'.
      When the insertion was velamentous, the sonographer was instructed to indicate
      whether or not it was vasa previa. The sonogram obtained at 18-20 weeks'
      gestation was used for comparison with outcome data. RESULTS: Cord insertion was
      visualized by color Doppler imaging in 99.8% (586/587) of the fetuses in our
      study. The mean time required for examination was 20 s and, in 95% of the cases,
      cord insertion was visualized within 1 min. The sonographic identification of
      velamentous cord insertion had a sensitivity of 100% (5/5), a specificity of
      99.8% (580/581), a positive predictive value of 83% (5/6) and a negative
      predictive value of 100% (580/580). In our study, vasa previa was diagnosed at 18
      gestational weeks in two cases and, in one of the cases, vasa previa was
      confirmed at delivery. CONCLUSIONS: We could consistently identify cord insertion
      and velamentous cord insertion with color Doppler imaging during routine
      sonography in the mid-trimester. Transvaginal color Doppler imaging and serial
      scans were needed to identify vasa previa.

PMID- 9918093
TI  - Poor perinatal outcome associated with vasa previa: is it preventable? A report
      of three cases and review of the literature.
AB  - We describe three cases of vasa previa and review the English-language literature
      for all cases reported since 1980. Antenatal diagnosis was significantly
      associated with decreased fetal mortality (p = 0.033). A low-lying placenta is a
      risk factor for vasa previa, as it occurred in 81% of patients.

PMID- 9918094
TI  - A strategy for reducing the mortality rate from vasa previa using transvaginal
      sonography with color Doppler.
AB  - Vasa previa is a cause of sudden unanticipated fetal death, with a fetal
      mortality of 33-100%. Transvaginal sonography (TVS) and color Doppler may aid in
      making the diagnosis antenatally, allowing elective Cesarean delivery, thereby
      avoiding fetal death from exsanguination which would occur if the membranes were
      allowed to rupture in labor. Whilst it is not feasible to screen all pregnant
      women for vasa previa, antenatal examination with TVS and color Doppler of women
      at risk, specifically those with low-lying placentas, bi-lobed, multi-lobed and
      succenturiate-lobed placentas, multiple pregnancies and pregnancies resulting
      from in vitro fertilization may lead to antenatal diagnosis of the condition. We
      present the last three cases of vasa previa to have occurred in our institution,
      two of which were diagnosed antenatally using TVS and color Doppler. In all three
      cases, routine 20-week obstetric sonography revealed low-lying placentas; in only
      one of these did the placenta remain low at term. A low-lying placenta at 20
      weeks may be a risk factor for vasa previa; we suggest that further studies be
      carried out to ascertain this. Judicious use of TVS and color Doppler in women
      considered at risk of vasa previa may help to reduce the mortality from this
      condition.

PMID- 9918095
TI  - Fetal gallstones: sonographic and clinical observations.
AB  - Fetal gallstones were visualized sonographically in two cases at 30 and 37 weeks'
      gestation; follow-up scans at 2 and 3 months, respectively, disclosed their
      spontaneous resolution. The hypotheses advanced to explain the formation of
      echogenic material in the fetal gallbladder are reviewed, and the clinical
      utility of postnatal long-term sonographic follow-up is stressed.

PMID- 9918096
TI  - Prenatal diagnosis of atypical cystic lesions of the fetal scalp.
AB  - Two cases of cystic lesions of the fetal scalp are described. They were initially
      thought to be meningoceles, but the brain was normal on ultrasound examination
      and there were no associated abnormalities. In the first case, by 26 weeks'
      gestation, the original cystic lesion had regressed to a dense tissue mass; in
      the second case, the cyst remained as a small anechoic mass. Postnatal assessment
      in the first case revealed a plexiform skin lesion measuring 40 x 15 mm on the
      left parietal bone. This was mobile and not attached to the underlying
      structures. The skull showed no obvious defect and a cranial scan was normal. In
      the second case, an epidermal cyst was diagnosed.

PMID- 9918097
TI  - Significance of echogenic foci in the fetal heart.

PMID- 9918098
TI  - Differences in epithelial morphology correlate to Na(+)-transport: a study of the
      proximal, mid, and distal regions of the coprodeum from hens on high and low NaCl
      diet.
AB  - A study was performed to correlate regional morphology and amiloride inhibitable
      Na(+)-transport in the coprodeal epithelium in hens, Gallus domesticus, on low
      NaCl diet and in controls. Proximal (close to colon), mid and distal (close to
      urodeum) regions were examined using light microscopy, transmission- and scanning
      electron microscopy. Na(+)-transport was measured electrophysiologically in
      Ussing-chambers in the proximal and distal regions. The epithelium, simple and
      columnar, is composed of absorptive intestinal epithelial cells, goblet cells,
      brush cells, migrating lymphoid cells, and enteroendocrine cells. Brush cells,
      identified in avians for the first time, occur in highest number in the proximal
      part of the coprodeum in low-NaCl hens. Na(+)-transport is high in the low-NaCl
      hens, ranging from 347 microA/cm2 (proximal) to 187 microA/cm2 (distal). In
      control hens, which correspond to hens on high-NaCl diet, it is low in all
      regions (0-4 microA/cm2). Absorptive intestinal epithelial cells as well as brush
      cells adapt to variations in transepithelial Na(+)-transport by regulating height
      and packing density of their microvilli, number, size, and localization of apical
      vesicles, and the width of the intercellular space. Regional differences in the
      epithelial cell composition and ultrastructure are closely correlated to
      transepithelial Na(+)-transport but only in low-NaCl hens, as controls do not
      show these variations.

PMID- 9918099
TI  - Palmar and plantar pads and flexion creases of genetic polydactyly mice (Pdn).
AB  - Attempts to gain a better understanding of the relationship between the epidermal
      ridge patterns (dermatoglyphics) and flexion creases on the volar aspects of
      human hands and feet and specific medical disorders led to a search for a
      suitable animal model, allowing studies of the fetal development of the pertinent
      structures. A common experimental animal, the rat (Rattus norvegicus), was found
      to be an excellent candidate, owing to the strong resemblance of the volar pads
      and flexion creases on its palmar and plantar surfaces to those of human
      subjects. A hereditary preaxial polydactyly mouse (Pdn) provides an opportunity
      to study the effects of this malformation on the surrounding morphological
      structures and, specifically, on the volar pads, i.e., the sites over which the
      dermatoglyphic patterns develop. The hands and feet of the wild-type (+/+) mice
      show no anomalies, and their major pad and flexion crease configurations
      correspond to those of normal rats. The heterozygous (Pdn/+) mice, in spite of
      having a thumb/big toe with a duplicated distal phalanx on their hands/feet, did
      not display any alterations in palmar/plantar pads. The homozygous (Pdn/Pdn) mice
      have a protrusion in the thenar area and one to three supernumerary digits on the
      preaxial portion of both the hands and feet. The effect of these anomalies was
      found to be limited to the pad and flexion crease configurations in the preaxial
      areas; the postaxial sites were not affected. The original number of pads on the
      thenar/first interdigital areas of Pdn/Pdn mice was apparently identical to that
      of the +/+ and Pdn/+mice. The preaxial protrusion, however, affected the number,
      size, and location of the pads observed in the newborn mice, resulting in varying
      pad configurations, such as fused and scattered pads or a pad cluster formed by
      gathering the neighboring pads. These pad modifications were induced by the
      preaxial plantar/palmar protrusion only and were not affected by the presence of
      supernumerary preaxial digits. In view of the similarities in the morphology and
      fetal development of human and mouse distal limbs, the present study is relevant
      to human subjects, particularly to the understanding of the significance of
      dermatoglyphic variations in individuals with specific medical disorders. Future
      studies of naturally occurring or experimentally induced limb malformations in
      mice or rats should provide valuable insights into the development of human hands
      and feet and into factors contributing to their congenital anomalies.

PMID- 9918100
TI  - Dentist-prescribed home bleaching: current status.
AB  - White teeth have been an indicator of physical attractiveness throughout history.
      Only recently have we been able to whiten teeth with few side effects, making
      tooth bleaching a popular and effective dental treatment. The American Dental
      Association (ADA) has established guidelines on safety and effectiveness for
      tooth bleaching. External stains from aging or inherent dark color are more
      responsive to bleaching than internal stains. Dentist-prescribed home bleaching-
      including a careful dental exam, custom-fabricated trays, tacky high-viscosity
      gels, adequate instructions, and recall exams--has been shown to be an effective
      method for bleaching teeth. Trays can be worn overnight or during the day with
      similar effectiveness. The bleaching effect can last up to 3 years with more than
      50% success.

PMID- 9918101
TI  - Efficacy, longevity, side effects, and patient perceptions of nightguard vital
      bleaching.
AB  - Since its introduction into dentistry in 1989, nightguard vital bleaching has
      been proven to be a simple and safe procedure to whiten discolored teeth.
      Efficacy of the technique is 95% for nontetracycline-stained teeth, and with
      extended treatment time, tetracycline-stained teeth can be expected to lighten in
      90% of cases. Satisfactory retention of the shade change can be expected in 63%
      of patients 3 years posttreatment and at least 35% at 7 years. Side effects are
      usually mild and transient, disappearing within days of treatment completion.
      Patients report that they are glad they went through the procedure, and 97%
      recommend the procedure to a friend.

PMID- 9918102
TI  - Tooth bleaching using peroxide-containing agents: current status of safety
      issues.
AB  - During the last 10 years, at-home tooth bleaching using peroxide-containing
      agents has quickly become well accepted. It is one of the most popular cosmetic
      dental procedures for whitening teeth. Although there are few disputes regarding
      their efficacy, concerns and debates have continued regarding the safety of
      peroxide-containing tooth bleaching agents. Potential carcinogenicity and
      genotoxicity of the peroxides used in bleaching agents are the two most
      persistent and controversial issues. This article reviews and discusses available
      information on carcinogenicity and genotoxicity of hydrogen peroxide and the
      potential risks associated with the use of peroxide-containing bleaching agents.
      Clinical studies reported after the 1996 international symposium on responses of
      oral tissues to peroxide-containing bleaching agents are also reviewed. Overall
      evidence supports the conclusion that the proper use of peroxide-containing at
      home tooth bleaching agents is safe. However, potential adverse effects may occur
      in inappropriate applications, abuses, or the use of inappropriate products. At
      home tooth bleaching should be monitored by dental professionals to maximize the
      benefits while minimizing potential risks.

PMID- 9918103
TI  - The applications and integration of at-home bleaching into private dental
      practice.
AB  - Since the introduction of home bleaching, the "whitening" of teeth has become
      much more common. This article describes at-home bleaching and the integration of
      this new treatment modality into the private dental practice. Case reports of the
      use of bleaching with and without restorative dentistry are presented, as well as
      tips on patient education and the timing of therapy.

PMID- 9918104
TI  - Nightguard bleaching to lighten a restored, nonvital discolored tooth.
AB  - Traditional techniques to lighten discolored endodontically treated teeth have
      used bleaching materials that had to be applied and directly monitored by
      dentists. These bleaching techniques have been associated with cervical
      resorption in nonvital teeth, and the treatment outcome is often difficult to
      predict. This article describes the use of nightguard bleaching to obtain an
      esthetic result for a restored nonvital tooth that had been treated with limited
      success with traditional office-based bleaching procedures.

PMID- 9918106
TI  - At-home use of 35% carbamide peroxide bleaching gel: a case report.
AB  - When 10% carbamide peroxide is inefficient for stubborn stains and the patient
      experiences no sensitivity, higher concentrations (up to 35%) may resolve the
      discoloration.

PMID- 9918105
TI  - Effects of bleaching on teeth and restorations.
AB  - This article describes how at-home bleaching procedures affect teeth and
      restorative materials. Specifically, it discusses the effects of tooth-whitening
      systems on enamel surfaces, enamel and dentin bond strengths, marginal integrity,
      color, and other properties of restorative materials.

PMID- 9918107
TI  - Making a clinical decision for vital tooth bleaching: at-home or in-office?
AB  - The dramatic increase in public demand for esthetic dentistry and tooth bleaching
      has encouraged development and resulted in new products and eltasdeltaues. Vital
      tooth bleaching, including in-office bleaching and at-home bleaching, has been
      adopted as an effective and safe method for whitening natural dentition. Although
      most dentists prefer at-home bleaching, nearly one third use in-office bleaching.
      Continuous improvements in bleaching products and delivery systems have made in
      office bleaching more practical and predictable. This article discusses the
      practical applications of vital tooth bleaching, as well as the advantages and
      disadvantages of each method.

PMID- 9918108
TI  - Phosphorothioate hammerhead ribozymes targeting a conserved sequence in the V3
      loop region inhibit HIV-1 entry.
AB  - Seven different phosphorothioate DNA-RNA chimeric hammerhead ribozymes (RzV3-nT,
      n = 1-7) targeted against the V3 loop region of HIV-1 were synthesized. Two of
      these, RzV3-1T and RzV3-3T, efficiently cleaved transcribed envelope RNA of HXB2
      in vitro. The target sequence of RzV3-1T belongs to a conserved region and is
      completely identical in the HIV-1 HXB2, NL432, and ADA strains. Furthermore, RzV3
      1T cleaved the envelope RNA of HIV-1 SF162 with a single base substitution in the
      distal site. U87 cells expressing CD4 and coreceptors were used as target cells
      for infections with the SF162 and NL432 strains. Replication of both the NL432
      and SF162 strains in RzV3-1T-treated cells was significantly lower than that in
      control cultures. Envelope gene product formation was measured quantitatively
      with a single-cycle infection assay using pseudovirus generated from
      cotransfection with one vector containing a luciferase reporter gene and one
      vector containing the envelope gene of HXB2, SF162, or ADA. Production of
      pseudovirus in RzV3-1T-treated cells led to a marked (93% or 87%) inhibition of
      envelope-mediated entry of resultant HXB2-derived or ADA-derived pseudotype
      virions, respectively, and a moderate (44%) inhibition was seen for SF162-derived
      pseudotype virions. Thus, an efficient, stable ribozyme against a functionally
      important region of HIV-1 was identified by evaluating its activities in vitro
      and in vivo. This ribozyme may be useful for control of HIV-1 infection.

PMID- 9918109
TI  - Cellular distribution of phosphorothioate oligonucleotide following intravenous
      administration in mice.
AB  - Oligonucleotides are promising therapeutic agents for the prevention or treatment
      of a variety of diseases. The therapeutic potential of oligonucleotide therapy
      depends greatly on the bioavailability of oligonucleotides to their target cells
      and organs. We previously reported the pharmacokinetics and distribution of
      phosphorothioate oligonucleotide in mice using [35S]-labeled oligonucleotide
      ([35S]-oligo). To extend this study, we administered 30 mg/kg of fluorescent
      labeled oligonucleotide (FITC-oligo) to mice and examined oligonucleotide
      distribution by measuring the fluorescence intensity in various cells and tissues
      using flow cytometry. Following FITC-oligo administration, fluorescence was
      detected in all the tissues examined. In terms of the fluorescent intensity,
      accumulation was greatest in liver and kidney, intermediate in spleen and bone
      marrow, and very low in peripheral blood mononuclear cells (PBMC). At 4 hours
      after administration, the level of oligonucleotide uptake in PBMC, spleen
      lymphocytes, and bone marrow cells revealed the following pattern:
      monocytes/macrophages > B cells > T cells. Confocal microscopy detected
      intracellular fluorescence in PBMC prepared under the same conditions as those
      for flow cytometry. These studies provide a rationale for designing cell targets
      for antisense therapeutics.

PMID- 9918110
TI  - Treatment of duck hepatitis B virus by antisense poly-2'-O-(2,4-dinitrophenyl)
      oligoribonucleotides.
AB  - The poly-2'-O-(2,4-dinitrophenyl)-oligoribonucleotide (poly-DNP-RNA) with
      antisense sequence 5'ggguguauggaaaagccguc-3' was designed to target the sequence
      2468-2487 in the polymerase gene of duck hepatitis B virus (DHBV). The
      stereochemically pure RNA was synthesized by using T7 RNA polymerase with
      synthetic DNA template and subsequently derivatized with 2,4-dinitrofluorobenzene
      in mild basic conditions to make the poly-DNP-RNA with an average DNP/base ratio
      of 0.7. In vitro studies showed that this antisense poly-DNP-RNA can hybridize
      with sense DNA and has high resistance to RNase A digestion. These poly-DNP-RNA
      were also found to be potent sequence-independent inhibitors of the reverse
      transcriptase activity of DHBV DNA-polymerase. For in vivo studies, DHBV-infected
      ducks were treated with antisense, sense, and random noncomplementary sequence
      poly-DNP-RNA, respectively. The data showed that the antisense poly-DNP-RNA
      completely inhibited the duck viremia in all nine ducks that had been treated
      with a dose of 1 mg/kg (i.v.) per day for 25 days. The viremia did not come back
      after 10 months recession. In the sense group, three of the four ducks showed no
      inhibition, and in the random group, both ducks maintained their viremia. After
      45 days of treatment with the antisense poly-DNP-RNA, followed by 2 weeks of
      recession, PCR as well as QC-PCR assay and microscopic examination showed that
      viral DNA had disappeared in liver and that the histology of the damaged liver
      (filled with fat granules) had returned to normal.

PMID- 9918111
TI  - A fluorescent base analog for probing triple helix formation.
AB  - Benzo[g]quinazoline-2,4-(1H,3H)-dione (BgQ), a fluorescent thymine analog, was
      incorporated into an oligopyrimidine (III) able to give rise to a triple-stranded
      structure by clamping a purine 11-mer (I). The formation of the I-III complex
      resulted in both a shift of the fluorescence emission maximum and a decreased
      fluorescence intensity. No such variations were observed on the formation of a
      Watson-Crick duplex between I and the complementary strand in which a T residue
      was substituted for BgQ. Therefore, the fluorescence emission of BgQ can be used
      to selectively monitor the formation of triple helices.

PMID- 9918112
TI  - Formation of stable DNA triple helices within the human bcr promoter at a
      critical oligopurine target interrupted in the middle by two adjacent
      pyrimidines.
AB  - Antigene strategies based on the use of triplex-forming oligonucleotides (TFO) as
      artificial repressors are constrained by the need for genomic targets with a
      polypurine-polypyrimidine [poly (R.Y)] DNA motif. In this study, we demonstrate
      that both A/G and G/T motif oligonucleotides recognize and bind strongly to a
      critical polypurine sequence interrupted in the middle by two adjacent cytosines
      and located in the promoter of the human bcr gene at the transcription
      initiation. The interaction between the designed TFO and this irregular poly
      (R.Y) target has been studied using a number of techniques, including
      electrophoretic mobility shift assay (EMSA), circular dichroism (CD), DNase I,
      and dimethyl sulfate (DMS) footprinting. Although CD shows that the 24-mer TFO
      self-aggregate in solution, they bind to the bcr target at 37 degrees C, forming
      stable triplexes that do not dissociate during electrophoretic runs performed up
      to 50 degrees C in 50 mM Tris-acetate, pH 7.4, 10 mM MgCl2, 50 mM NaCl (buffer
      A). We used EMSA to determine the equilibrium dissociation constants (Kd) for the
      reaction T <==> D + TFO at 37 degrees C, either in buffer A or in 50 mM Tris
      acetate, pH 7.4, 10 mM MgCl2, 5 mM NaCl (buffer B). The triplexes were found to
      be more stable in buffer B, a behavior that can be rationalized in terms of
      monovalent and divalent cation competition for binding to DNA. Footprinting
      experiments showed that the TFO interact with the irregular poly (R.Y) target in
      a highly sequence-specific way and that the A/G motif oligonucleotide,
      juxtaposing T to the double CG inversions of the target, formed the most stable
      triplex (e.g., 1 microM TFO promoted strong footprints at 37 degrees C). These
      triplexes, except the one containing two A.C.G mismatched triads, are not
      destabilized under near physiologic conditions, that is, in 50 mM Tris-acetate,
      pH 7.4, 80 mM KCl, 20 mM NaCl, 2 mM spermidine. Moreover, we found that guanine
      N7 in T.C.G and guanine N7 in A.C.G are both accessible to DMS and that the first
      is less reactive than the second. In conclusion, the results of this study
      indicate that a critical sequence in the human ber promoter may be used as a
      potential binding site for TFO designed to repress artificially the transcription
      of the fused bcr/abl gene expressed in leukemia cells.

PMID- 9918113
TI  - Enhanced downregulation of the p75 nerve growth factor receptor by cholesteryl
      and bis-cholesteryl antisense oligonucleotides.
AB  - The effects of conjugating cholesterol to either or both ends of a
      phosphorothioate (PS) oligonucleotide were analyzed in terms of cellular uptake
      and antisense efficacy. The oligo sequence was directed against the p75 nerve
      growth factor receptor (p75), and was tested in differentiated PC12 cells, which
      express high levels of this protein. The addition of a single cholesteryl group
      to the 5'-end significantly increased cellular uptake and improved p75 mRNA
      downregulation compared with the unmodified PS oligo. However, only a minor
      degree of downregulation of p75 protein was obtained with 5' cholesteryl oligos.
      Three different linkers was used to attach the 5' cholesteryl group but were
      found not to have any impact on efficacy. Addition of a single cholesteryl group
      to the 3'-end led to greater p75 mRNA downregulation (31%) and p75 protein
      downregulation (28%) than occurred with the 5' cholesteryl oligos. The biggest
      improvement in antisense efficacy, both at the mRNA and protein levels, was
      obtained from the conjugation of cholesterol to both ends of the oligo. One of
      the bischolesteryl oligos was nearly as effective as cycloheximide at decreasing
      synthesis of p75. The bis-cholesteryl oligos also displayed significant efficacy
      at 1 microM, whereas the other oligos required 5 microM to be effective. The
      enhanced efficacy of bis-cholesteryl oligos is likely to be due to a combination
      of enhanced cellular uptake and resistance to both 5' and 3' exonucleases.

PMID- 9918114
TI  - Unusual interactions between cleavage products of a cis-cleaving hammerhead
      ribozyme.
AB  - We have synthesized and tested a cis-cleaving ribozyme designed to have
      thermodynamically stable stem-loop structures. This cis-ribozyme cleaves very
      efficiently in vitro, with a cleavage rate of about 0.5/min. Surprisingly, during
      the course of in vitro transcription and cleavage of our ribozyme, a product of
      unusual mobility accumulates and coincides with a sharp decline in the rate of
      formation of cleavage products. Analyses of this electrophoretic variant
      demonstrated that it is formed by interactions of the cleavage products. Despite
      the fact that the products and ribozyme transcript are of identical sequence, the
      cleavage products interact only with one another and not with the uncleaved
      precursor. This suggests a significant structural difference between the cleaved
      and uncleaved ribozyme transcripts. Testing of this cis-ribozyme in both yeast
      and mammalian cells shows no significant cleavage activity in vivo. We conclude
      that the structure of the ribozyme flanking sequences is important for optimizing
      the rate of ribozyme cleavage, but this enhanced rate does not necessarily
      correlate with enhanced in vivo function.

PMID- 9918115
TI  - Secondary structure dimorphism and interconversion between hairpin and duplex
      form of oligoribonucleotides.
AB  - RNA hairpins can alternatively form a dimer with a bulged loop flanked by
      regularly base paired regions. [1H]NMR spectroscopy and native gel
      electrophoresis were used to study how the sequence of nucleotides in the loop of
      the hairpin affect the hairpin-duplex interconversion. As a model system, a
      hairpin containing 7 nucleotides in the loop and 5 base pairs in the stem was
      used. The loop size was gradually reduced from 7 to 4 nucleotides, yielding
      finally the stable UNCG tetraloop. Single nucleotide mutations were performed to
      investigate the influence of the self-complementarity of the loop sequence on the
      dimerization. The results demonstrate that (1) the initial fraction of hairpin is
      determined by concentration of the oligonucleotide, the annealing procedure, and
      the relative stability of the loop, (2) the degree of self-complementarity of the
      loop sequence of the hairpin governs the dimerization kinetics, and (3)
      oligonucleotides complementary to the loop sequence decrease the dimerization
      rate. We propose a secondary structure-based model for the dimerization reaction
      of RNA hairpins in which the formation of intermolecular base pairs between self
      complementary nucleotides of the loops represents the nucleation step.

PMID- 9918116
TI  - Oligonucleotide-mediated inhibition of genomic RNA dimerization of HIV-1 strains
      MAL and LAI: a comparative analysis.
AB  - An essential step in the replication cycle of retroviruses is the dimerization of
      two copies of the genomic RNA. In vitro and in vivo studies have demonstrated
      that dimerization is mediated at least partially by RNA-RNA interactions. In HIV
      1, the cis-element most important for dimerization is the dimerization initiation
      site (DIS), a stem-loop structure with an autocomplementary loop located between
      the primer binding site and the splice donor site in the 5' leader region of
      genomic RNA. We have studied the inhibition of dimerization of RNA corresponding
      to the first 615 nt of HIV-1 strains MAL and LAI in vitro using RNA and DNA
      oligonucleotides. The oligonucleotides were identical to or complementary to the
      DIS of the MAL and LAI strains, which are representative of the two most common
      DIS motifs found in natural isolates. The loop sequence of the DIS of the MAL
      isolate is AGGUGCACA, and that of the LAI sequence is AAGCGCGCA (the
      autocomplementary sequences are GUGCAC and GCGCGC, respectively). Several of the
      oligonucleotides were very efficient inhibitors of dimerization. However,
      homologous oligonucleotides displayed vastly different inhibition efficiencies
      between the two strains despite relatively modest sequence differences. Some of
      the oligonucleotides bound the viral RNA via a loop-loop interaction alone,
      whereas others recruited stem nucleotides to form an extended duplex even in the
      absence of loop complementarity. Furthermore, oligonucleotide inhibition was
      ineffective at low temperature, suggesting that a conformational change in the
      DIS is necessary for disruption of the dimeric structure of the DIS or binding of
      oligonucleotide or both.

PMID- 9918117
TI  - Failure to achieve gene conversion with chimeric circular oligonucleotides:
      potentially misleading PCR artifacts observed.
AB  - Recently, a novel strategy for nucleotide exchange of target DNA using chimeric
      RNA/DNA oligonucleotides (CO) was reported. The CO can easily be transfected into
      cells, remain stable within the cells, and migrate to the nucleus. We have in
      this study used 42 similar constructs for targeting six different human and
      canine loci. A variety of cationic lipids, electroporation, and microinjection
      were used for transfection of the CO into lymphoblastoids, Huh7, HT 1080, and
      Jurkat cell lines, and canine primary fibroblasts and hepatocytes. However, no
      nucleotide exchange was detected in any of the targeted loci. Using PCR followed
      by restriction enzyme analysis, nucleotide exchange in approximately 2%-10% of
      the PCR products was observed during the first 3 days after transfection with CO
      vWF-28S2 designed for repairing a mutation in the von Willebrand gene.
      Surprisingly, the observed exchange reverted after culturing the cells for a
      longer period of time (14 days). Furthermore, a positive indication of gene
      conversion (5%) was also obtained using an allele-specific PCR method for
      analysis of the PAI-1 gene. However, cloning of the PCR products revealed no
      nucleotide exchange. In our view, the most likely explanation is that the initial
      false positive result originates from a PCR artifact created by the CO itself.
      Our results imply that an independent method, that is, Southern blotting, must be
      used to verify an observed nucleotide exchange.

PMID- 9918118
TI  - Semantics, inflammation, cytokines and common sense.
AB  - Semantic evaluation of some of the terms we regularly employ--inflammation, anti
      inflammatory, pro-inflammatory, anti-inflammatory drugs, cytokines, homeostasis
      and stress--raises concerns about their precise meanings and about their
      mechanistic implications. Semantic imprecision may have undesirable conceptual
      consequences.

PMID- 9918119
TI  - The CIS family: negative regulators of JAK-STAT signaling.
AB  - A family of cytokine-inducible SH2 proteins (CISs) has recently been identified
      and the members are growing in number. In this family, the central SH2 domain and
      approximately 40 amino acids at the C-terminus (CIS homology domain; CH domain)
      are well conserved, while the N-terminal region shares little similarity and
      varies in length. Most CISs appear to be induced by several cytokines and at
      least three of them (CIS1, CIS3 and JAB) negatively regulate cytokine signal
      transduction. Forced expression of CIS1 inhibits STAT5 activation by binding of
      CIS1 to cytokine receptors, and CIS3 and JAB directly bind to the kinase domain
      of JAKs, thereby inhibiting kinase activity. Therefore, these CIS family members
      seem to be present in a classical negative feedback loop of cytokine signaling.
      They may also play a role in the mutual suppression of cytokine actions
      frequently found in immune and inflammatory responses. Precise molecular
      mechanisms of the signal inhibition and their physiological functions will be
      addressed in the near future. The CH domain is also found in several interesting
      genes containing WD-40 repeats, SPRY domains, ankyrin repeats, and GTPases.
      However, the function of the CH domain remains to be determined.

PMID- 9918120
TI  - Nuclear import and export of proteins: the molecular basis for intracellular
      signaling.
AB  - A family of latent cytoplasmic transcription factors termed Stats are activated
      by a variety of cytokines, and are then translocated into the nucleus where they
      activate transcription. Recent advances in nuclear protein import have shown that
      the extracellular signal-dependent nuclear import of Stat1 is mediated via
      complex formation with NPI-1 (a member of the alpha subunit family) and the beta
      subunit of the nuclear pore-targeting complex, and a small GTPase, Ran. The
      unique transport pathway of Stat1, which is different from that of the SV40T
      antigen, indicates that a complex divergence exists in the function of transport
      factors and transport pathways.

PMID- 9918121
TI  - Peyer's patch organogenesis as a programmed inflammation: a hypothetical model.
AB  - Gene-knock-out studies implicate roles of lymphotoxin (LT) alphabeta and LT betaR
      in the initial phase of Peyer's patch (PP) organogenesis. We recently identified
      the requirement of IL-7R alpha/gamma c/Jak3 signal in LT alphabeta production of
      IL-7R alpha+ cells. These observations lead us to a hypothetical model for PP
      organogenesis with three cellular components. The first is the producer of the
      ligand for IL-7R alpha, which then stimulate the IL-7R alpha+ cells to produce LT
      alphabeta activating the LT betaR+ cells to form an organizing center for PP
      organogenesis. This model is similar to that of inflammation, suggesting that PP
      organogenesis is a programmed version of inflammation.

PMID- 9918122
TI  - The interleukin 1 receptor: ligand interactions and signal transduction.
AB  - The interleukin 1 (IL-1) receptor is a critical component in mediating the
      inflammatory responses of IL-1, which affect nearly every cell type. Recently,
      major inroads have been made toward understanding the mechanism by which IL-1
      interacts with its receptor and activates signal transduction. The receptor
      ligand association has been visualized by X-ray crystal structure analysis,
      revealing intimate details that distinguish IL-1beta from the naturally-occuring
      receptor antagonist. Signaling studies have focused primarily on the ability of
      IL-1 to transduce the activation of the transcription factor, NF-kappaB, which is
      of central importance to inflammatory and immune responses. Virtually all of the
      effort has targeted the activation of a kinase which results in the
      phosphorylation of the inhibitory IkappaB molecule at two serines that precedes
      the proteolytic degradation of this inhibitor and the release of active NF
      kappaB. The recent characterization of an IL-1 receptor associated kinase (IRAK)
      and a continuous molecular path between this kinase and that which directly
      phosphorylates IkappaB would seem to all but close the basic understanding of IL
      1 receptor signal transduction. However, at least half of the IL-1-dependent NF
      kappaB activation is independent of IRAK and uses a novel pathway involving the
      recruitment of phosphatidylinositol 3-kinase (PI3K) to a distinct site within the
      cytoplasmic domain of the IL-1 receptor. This novel pathway for NF-kappaB
      activation and the fact that other important transcription factors are also
      activated by an IL-1 receptor-dependent signal event, clearly defines additional
      mechanisms that influence inflammation.

PMID- 9918123
TI  - Pharmacological modulation of cytokine action and production through signaling
      pathways.
AB  - The action or production of cytokines is mediated through a number of signal
      transduction pathways which have been elucidated recently. These include pathways
      integrating the activation of extracellular receptors and subsequent
      intracellular events leading to alterations of gene expression, cytoskeletal
      organization, DNA synthesis and cell survival, and the direct activation of
      intracellular transcription factors via cell permeable hormones. Discovery and
      characterization of many of these pathways has been aided by the use of compounds
      which inhibit them. In turn the inhibitors, many of which are already in the
      clinic, have provided significant insight into the pharmacological importance of
      each pathway and its potential for providing more potent, selective and safer
      alternatives. This review summarizes the current state of knowledge about several
      of these pathways, how they regulate cytokine action or production, and their
      potential for pharmacological intervention.

PMID- 9918125
TI  - IL-12 and viral infections.
AB  - Interleukin-12 activates natural killer cells and promotes the differentiation of
      Th1 CD4+ cells; it is a critical factor in viral immunity. IL-12 is secreted by
      antigen presenting cells including dendritic cells, macrophages and astrocytes,
      both in tissues and in secondary lymphoid organs. Experimental studies have shown
      that administration of the cytokine rapidly activates both innate and specific
      immune responses; this results in enhanced host cellular responses and generally,
      promotes clearance of virus and host recovery from infection. The observations of
      many laboratories, studying viral immunity to both RNA and DNA based pathogens,
      are summarized.

PMID- 9918124
TI  - Cytokine actions in the central nervous system.
AB  - Cytokines and chemokines have been implicated in contributing to the initiation,
      propagation and regulation of immune and inflammatory responses. Also, these
      soluble mediators have important roles in contributing to a wide array of
      neurological diseases such as multiple sclerosis, AIDS Dementia Complex, stroke
      and Alzheimer's disease. Cytokines and chemokines are synthesized within the
      central nervous system by glial cells and neurons, and have modulatory functions
      on these same cells via interactions with specific cell-surface receptors. In
      this article, I will discuss the ability of glial cells and neurons to both
      respond to, and synthesize, a variety of cytokines. The emphasize will be on
      three select cytokines; interferon-gamma (IFN-gamma), a cytokine with
      predominantly proinflammatory effects; interleukin-6 (IL-6), a cytokine with both
      pro- and anti-inflammatory properties; and transforming growth factor-beta (TGF
      beta), a cytokine with predominantly immunosuppressive actions. The significance
      of these cytokines to neurological diseases with an immunological component will
      be discussed.

PMID- 9918126
TI  - Cytokines in implantation.
AB  - Implantation is a complex process which involves the 'invasion' of the maternal
      endometrium by the trophoblast surrounding the developing blastocyst. In response
      to this interaction there is a cellular reaction within the endometrium which has
      some features analogous to invasion by a tumour and some which are more
      characteristic of an inflammatory response. In addition, and also in common with
      cancer and inflammation, there is a release of biologically active molecules,
      including cytokines, at and around the implantation site. The information on
      cytokines is complex and often contradictory but it is recognised that they play
      an important role in the successful establishment of pregnancy. The evidence for
      this role is examined in this review.

PMID- 9918127
TI  - Tumor necrosis factors in 1998.

PMID- 9918128
TI  - Nomenclature for human DPYD alleles.
AB  - To standardize DPYD allele nomenclature and to conform with international human
      gene nomenclature guidelines, an alternative to the current arbitrary system is
      described. Based on recommendations for human genome nomenclature, we propose
      that each distinct allele be designed by DPYD followed by an asterisk and an
      Arabic numeral. The number specifies the key mutation and, where appropriate, a
      letter following the number indicates an additional mutation on the mutant
      allele. Criteria for classification as a distinct allele are also presented.

PMID- 9918129
TI  - Individual sensitivity to cytogenetic effects of 1,2:3,4-diepoxybutane in
      cultured human lymphocytes: influence of glutathione S-transferase M1, P1 and T1
      genotypes.
AB  - Although some blood parameters have been suggested to modulate in-vitro induction
      of sister chromatid exchanges by 1,2:3,4-diepoxybutane (DEB), a metabolite of 1,3
      butadiene, the increased sensitivity has largely been assigned to a homozygous
      deletion of glutathione S-transferase T1 gene (GSTT1 null genotype). However,
      some DEB-sensitive individuals have been shown to be GSTT1 positive (having at
      least one undeleted GSTT1 allele). To examine potential causes for this overlap,
      we evaluated the effect of GSTM1, GSTP1, and GSTT1 genotypes, together with
      various life-style and blood parameters, on the DEB induction of sister chromatid
      exchanges and cells with chromosomal aberrations (aberrant cells) in lymphocyte
      cultures of 115 and 62 human donors, respectively. Our results supported the
      important role of the GSTT1 genotype in DEB sensitivity; 76% of cultures from
      GSTT1 null donors but only 4% of those from GSTT1 positive donors were DEB
      sensitive, as defined by sister chromatid exchange measurements. The GSTT1
      genotype also clearly affected DEB-induced aberrant cells, 92% of GSTT1 null and
      8% of GSTT1 positive donors being sensitive to DEB. All individuals showing a
      high response to DEB in both sister chromatid exchange and aberrant cell analyses
      were GSTT1 null. Baseline aberrant cell measurements but not sister chromatid
      exchange measurements were marginally higher among GSTT1 null donors compared
      with GSTT1 positive donors. GSTM1 and GSTP1 genotypes had no influence on these
      cytogenetic end-points. Blood transaminases, gamma-glutamyl transferase, urea,
      creatinine and white blood cell count showed a clear negative association with
      DEB-induced aberrant cells, whereas wine drinkers had more aberrant cells than
      non-drinkers. A higher sister chromatid exchange-response to DEB was observed in
      lymphocytes from women and smokers than from men and non-smokers, respectively.
      Erythrocyte count correlated negatively with DEB-induced sister chromatid
      exchanges. Thus, a variety of parameters seemed to modulate the individual DEB
      sensitivity together with the GSTT1 genotype. Although the known contributing
      factors accounted for a considerable part of individual variability in sister
      chromatid exchanges (59.4%) and aberrant cells (46.7%) in DEB treatment, they did
      not, however, fully explain the overlap in cytogenetic response between GSTT1
      positive and null individuals.

PMID- 9918130
TI  - The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of
      Parkinson's disease: a meta-analysis.
AB  - The association between the sparteine/debrisoquine (CYP2D6) oxidation
      polymorphism and the risk of Parkinson's disease was examined in a meta-analysis
      of case-control studies. The odds ratio was calculated for the risk of
      Parkinson's disease among poor metabolisers compared with extensive metabolisers.
      Twenty-one studies were identified of which six were excluded because they were
      not reported as full papers (n = 3), used incomplete genotype analysis (n = 2) or
      used Parkinson patients as both control individuals and cases (n = 1). The
      overall odds ratio was 1.48 (95% confidence interval 1.10-1.99). The odds ratio
      was 1.05 (95% confidence interval 0.63-1.77) in studies discriminating extensive
      and poor metabolisers by phenotyping (n = 8) and 1.67 (95% confidence interval
      1.11-2.50) in studies using genotyping (n = 7). This difference was caused by a
      single large study using genotyping. We conclude that there is no convincing
      evidence of an association between the debrisoquine/sparteine polymorphism and
      Parkinson's disease. However, it could prove worthwhile to perform another large
      study using genotyping.

PMID- 9918131
TI  - Lack of association between a polymorphism in the promoter region of the dopamine
      2 receptor gene and clozapine response.
AB  - Dopamine receptors are strong candidates for involvement in schizophrenia and are
      targeted by a wide variety of antipsychotics. We hypothesized that genetic
      variation in these neurotransmitter receptors may influence clinical response to
      clozapine, an antipsychotic which displays high affinity for dopamine D2
      receptors in the limbic system. To test this hypothesis, we studied a functional
      polymorphism in the promoter region of the D2 receptor gene (-141C Ins/Del) in a
      sample of 151 clozapine treated patients of British origin. In addition, the
      influence of this polymorphism on antipsychotic response in general was
      investigated on a sample of 146 Han Chinese schizophrenic patients treated with a
      variety of antipsychotics. No association was found between this polymorphism and
      clinical response in either of the two samples suggesting that genetic variation
      in D2 receptors does not play a major role in determining clinical response to
      antipsychotic treatment.

PMID- 9918132
TI  - Chromosomal linkage analysis of porphyria in mice induced by hexachlorobenzene
      iron synergism: a model of sporadic porphyria cutanea tarda.
AB  - Genetic susceptibility to toxic chemicals is of major importance but most studies
      concentrate on candidate genes and searches for unknown susceptibility genes are
      uncommon. Human sporadic porphyria cutanea tarda is usually precipitated by
      alcohol, oestrogens, hepatitis viruses, HIV or haemodialysis. The mechanism is
      not known but there is a role for iron metabolism and an underlying genetic
      predisposition is suspected. A similar porphyria in humans has also been caused
      by hexachlorobenzene. These human porphyrias can be modelled in iron-loaded mice
      exposed to hexachlorobenzene, in which C57BL/10ScSn is a prototype susceptible
      strain whereas DBA/2 mice are extremely resistant. A search for susceptibility
      genes was undertaken using complex trait analysis with DNA microsatellite markers
      of 'high' and 'low' responders from an F2 intercross. Correlation of markers with
      susceptibility, defined as accumulation of uroporphyrin in the liver, was
      assessed by chi-squared test for the proportion of C57BL/10ScSn and DBA/2 alleles
      present. Susceptibility loci on chromosomes 12, 14 and 17 were identified.
      Further analysis of markers on chromosomes 14 and 17 by MAPMAKER/EXP and
      MAPMAKER/QTL gave LOD scores of 7.3 and 3.6, respectively. Typing of chromosome
      12 for the Ahr gene, using a restriction fragment length polymorphism
      distinguishing between the b-1 and d alleles, gave significant but not perfect
      linkage. However, no strong association between alleles or expression of Cyp1a1/2
      genes, regulated by Ahr, and susceptibility for porphyria was detected. The
      results demonstrate that the porphyria induced by hexachlorobenzene in
      C57BL/10ScSn mice is a complex trait determined by at least three genes, which
      may be of relevance to susceptibility in the development of sporadic porphyria
      cutanea tarda and unknown aspects of liver damage.

PMID- 9918133
TI  - Role of glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes in
      modulating susceptibility to smoking-related lung cancer.
AB  - Glutathione S-transferases GSTM1, GSTM3, GSTP1 and GSTT1 are involved in the
      detoxification of active metabolites of several carcinogens in tobacco smoke. We
      studied the potential role of GSTM3 and GSTP1 gene polymorphisms either
      separately, or in combination with GSTM1 and GSTT1 gene polymorphisms, in
      susceptibility to lung cancer using peripheral blood DNA from 150 lung cancer
      patients and 172 control individuals, all regular smokers. The frequencies of
      GSTM3, AA, AB and BB genotypes were 70.7%, 24.0% and 5.3% in cases and 72.7%,
      24.4% and 2.9% in control individuals respectively. The frequencies of GSTP1, AA,
      AG and GG genotypes were 44.7%, 44.0% and 11.3% in cases and 50.0%, 37.2% and
      12.8% in control individuals respectively. When studied separately, neither GSTM3
      nor GSTP1 genotypes contributed significantly to the risk of lung cancer.
      Although failing to reach statistical significance, the combined GSTM3 AA and
      GSTP1 (AG or GG) genotype conferred a nearly threefold risk when the GSTM1 gene
      was concurrently lacking (odds ratio 2.9, 95% confidence interval 0.7-12.1).
      Significant interactions were observed between pack-years of smoking and the
      combined GSTM3 AA and GSTP1 (AG or GG) genotype, or the combined GSTM3 AA, GSTP1
      (AG or GG) and GSTM1 null genotype. The combination of these three a priori at
      risk genotypes conferred an increased risk of lung cancer among smokers with a
      history of at least 35 pack-years (odds ratio 2.7, 95% confidence interval 1.2
      6.0), but not in lighter smokers, probable because of the lower average number of
      pack-years of smoking found among control individuals with this genotype
      combination.

PMID- 9918134
TI  - p53 mutation spectrum in relation to GSTM1, CYP1A1 and CYP2E1 in surgically
      treated patients with non-small cell lung cancer.
AB  - p53 mutation status was analysed in relation to DNA polymorphisms of GSTM1,
      CYP1A1 and CYP2E1 from 105 surgically resected non-small cell lung cancer cases.
      Demographic factors, smoking, occupation, family history, tumour histology, grade
      and stage were taken into account. p53 mutations, detected either directly by DNA
      sequencing (P = 0.04, adjusted for smoking) or indirectly by immunostaining (P =
      0.06), were overrepresented among CYP1A1 variants. Mutations in exon 8 and
      transitions at CpG sites in the p53 gene were favoured in this subset. There was
      no relation between the individual gene polymorphisms or p53 mutations and
      disease-free survival by Kaplan-Meier analysis. The finding of excess CYP1A1
      heterozygotes in individuals with p53 mutations after adjustment for smoking
      suggests that CYP1A1 activation contributes to lung cancer via p53 inactivation.

PMID- 9918135
TI  - Relationship between polymorphism of N-acetyltransferase gene and susceptibility
      to colorectal carcinoma in a Chinese population.
AB  - Human hepatic N-acetyltransferase (NAT2) is subject to a genetic polymorphism.
      Because NAT2 is an important enzyme for the detoxification and/or bioactivation
      of several carcinogenic arylamines, it has been postulated that the polymorphism
      of NAT2 gene is associated with the occurrence of colorectal and bladder
      carcinomas. Several mutations have been described in the human NAT2 gene that
      have been associated with reduced NAT2 activity. However, the majority are single
      base substitutions at positions 481 (NAT2*5A), 590 (NAT2*6A) and 857 (NAT2*7A) of
      the NAT2 gene. This study was performed to evaluate the relative distribution of
      NAT2 alleles and genotypes in 216 colorectal carcinoma patients and 187 normal
      individuals. The frequencies of NAT2 alleles and genotypes in the sampled Chinese
      population were characterized by allele-specific polymerase chain reaction. No
      differences were observed in the distribution of the genotypes coding rapid
      acetylation (homozygous wild-type and heterozygous wild-type with any of the
      mutations) when comparing colorectal carcinoma patients with control individuals
      (P > 0.05). However, the rapid acetylation genotype was associated with cancer
      occurring on the right site of the colon. The frequencies of the NAT2*4, NAT2*5A,
      NAT2*6A and NAT2*7A alleles of the NAT2 gene (0.51, 0.07, 0.32 and 0.10,
      respectively) in control individuals were significantly different from those in
      patients (0.49, 0.06, 0.26 and 0.19, respectively, P < 0.01). There was a
      significant increase in the frequency of patients who were compound heterozygotes
      of NAT2*7A and a variant non-NAT2*7A allele. The NAT2*7A allele was also seen
      more frequently in distal cancer.

PMID- 9918136
TI  - Determination of the enzymes responsible for activation of the heterocyclic amine
      2-amino-3-methylimidazo[4,5-f]quinoline in the human breast.
AB  - The heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent
      mutagen and is a mammary carcinogen in rodents. In man, hepatic activation is
      carried out by cytochrome P450 (CYP) 1A2 and the ultimate DNA-reactive species is
      thought to be a nitrenium ion formed via an acetoxy ester of an exocyclic amino
      group. Because most human breast tumours are ductal in origin, we investigated
      the ability of cell types present in the mammary gland (breast epithelial cells
      and neutrophils present in milk) to activate IQ to DNA-binding species using 32P
      postlabelling. Phorbol myristate acetate-stimulated neutrophils produced a
      similar pattern of IQ-DNA adducts to that produced by human mammary epithelial
      cells. Adduct formation in stimulated neutrophils was inhibited 80% by the
      myeloperoxidase inhibitor sodium azide (1 mM) but was not affected by proadifen
      (100 microM), indomethacin (100 microM), or eicosatetraynoic acid (100 microM),
      inhibitors of cytochrome P450, prostaglandin synthetase, and lipoxygenase,
      respectively. Similar experiments in human mammary epithelial cells showed no
      azide inhibition of IQ-DNA adduct formation. Analysis of gene expression by
      reverse transcription-polymerase chain reaction showed that CYP1A1 and CYP1B1,
      but not CYP1A2, were expressed at detectable levels in untreated mammary
      epithelial cells, whereas in neutrophils cytochrome P450 expression was confined
      to low levels of CYP1A1. In cultured epithelial cells, IQ-DNA adduct formation
      and CYP1A1, but not CYP1B1 expression were induced threefold by benz[a]anthracene
      treatment; IQ-DNA adduct formation was inhibited by alpha-naphthoflavone. Our
      results indicate possible mechanisms for the metabolic activation of dietary
      carcinogens in the human breast.

PMID- 9918138
TI  - Detection and characterization of novel polymorphisms in the CYP2E1 gene.
AB  - To investigate whether interindividual variation in CYP2E1 levels can be
      explained by genetic polymorphism, we analysed DNA samples from 40 healthy
      individuals by single-strand conformational polymorphism analysis for
      polymorphisms in the CYP2E1 coding sequence and promoter region. DNA sequencing
      of samples showing mobility shifts on single-strand conformational polymorphism
      detected polymorphisms at positions -316 (A to G), -297 (T to A), -35 (G to T),
      1107 (G to C; intron 1), 4804 (G to A Val179Ile; exon 4) and 10157 (C to T; exon
      8). All individuals positive for either A(-316)G, G(-35)T, G(4804)A or the
      previously described RsaI polymorphism at -1019 were also positive for T(-297)A,
      which had the highest allele frequency of the observed polymorphisms (0.20). A(
      316)G, G(-35)T and G(4804)A were detected at allele frequencies of 0.022, 0.052
      and 0.013, respectively. The functional significance of the upstream
      polymorphisms was examined by preparing constructs of positions -549 to +3 of
      CYP2E1 containing the observed combinations of the polymorphisms fused to
      luciferase reporter genes and transfecting HepG2 cells. For the G(-35)T/T(-297)A
      construct, a 1.8-fold increase in luciferase activity compared with the wild-type
      sequence (P = 0.06) and 2.5-fold compared with T(-297)A only (P = 0.025) was
      observed. No significant difference in activity was observed between the other
      constructs. The significance of the predicted Val179Ile base change from G(4804)A
      was determined by expression of the wild-type and mutated full length cDNAs in
      lymphoblastoid cells. No significant difference in kinetic constants for
      chlorzoxazone hydroxylation between mutant and wild-type was observed. In
      summary, this study demonstrated six novel CYP2E1 polymorphisms, including three
      upstream of the promoter, but with the possible exception of G(-35)T, none
      appeared to be of functional significance.

PMID- 9918137
TI  - CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in
      Los Angeles.
AB  - CYP2D6 genotyping (CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*13, CYP2D6*16 alleles and
      gene duplications) was previously performed on 1053 Caucasian and African
      American lung cancer cases and control individuals and no significant difference
      in allele frequencies between cases and control individuals detected. We have
      carried out additional genotyping (CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9,
      CYP2D6*10, CYP2D6*17 alleles) and debrisoquine phenotyping on subgroups from this
      study to assess phenotype-genotype relationships. African-Americans showed
      significant differences from Caucasians with respect to frequency of defective
      CYP2D6 alleles, particularly CYP2D6*4 and CYP2D6*5. The CYP2D6*17 allele occurred
      at a frequency of 0.26 among 87 African-Americans and appeared to explain higher
      average metabolic ratios among African-Americans compared with Caucasians.
      CYP2D6*6, CYP2D6*8, CYP2D6*9 and CYP2D6*10 were rare in both ethnic groups but
      explained approximately 40% of higher than expected metabolic ratios among
      extensive metabolizers. Among individuals phenotyped with debrisoquine, 32 out of
      359 were in the poor metabolizer range with 24 of these (75%) also showing two
      defective CYP2D6 alleles. Additional single strand conformational polymorphism
      analysis screening of samples showing large phenotype-genotype discrepancies
      resulted in the detection of three novel polymorphisms. If subjects taking
      potentially interfering drugs were excluded, this additional screening enabled
      the positive identification of 88% of phenotypic poor metabolizers by genotyping.
      This sensitivity was comparable with that of phenotyping, which identified 90% of
      those with two defective alleles as poor metabolizers.

PMID- 9918139
TI  - Acetaminophen is an inhibitor of hepatic N-acetyltransferase 2 in vitro and in
      vivo.
AB  - Slow acetylators of the polymorphic N-acetyltransferase 2 (NAT2, EC 2.3.1.5)
      suffer more often from side-effects of NAT-substrates than fast acetylators.
      Since concomitant administration of drugs may inhibit NAT2, we studied the
      influence of acetaminophen on NAT2 in human hepatic cytosol in vitro and in
      healthy individuals. In-vitro acetylation was assessed in liver homogenate of one
      fast and one slow acetylator using sulfamethazine as a test substrate.
      Acetaminophen competitively inhibited sulfamethazine acetylation in fast and slow
      acetylator liver samples with Ki values of acetaminophen of 2144 micromol/l and
      712 micromol/l, respectively. In additional experiments, exposure of human liver
      cytosol to p-aminophenol, a putative precursor of acetaminophen in this reaction,
      revealed production of substantial amounts of acetaminophen, which indirectly
      suggests that acetaminophen may bind to the active site of NAT2. In-vivo
      acetylation was quantified with a urinary caffeine assay in 20 healthy volunteers
      at baseline and after repetitive oral administration of 1000 mg acetaminophen
      every 6 h for 1 day. The ratio of the acetylated caffeine metabolite acetyl-amino
      6-formylamino-3-methyluracil to 1-methylxanthine was reduced by 30.9% (range 11.0
      50.1%) in fast acetylators (n = 10) and by 19.3% (range 0.2-36.5%) in slow
      acetylators (n = 10). Acetaminophen, a widely used over-the-counter drug, which
      shares structural similarities with acetylated products, inhibits NAT2 both in
      vitro and in vivo. These findings suggest that even compounds which are not
      metabolized by NAT2 may inhibit the enzyme and reduce its metabolic capacity.

PMID- 9918140
TI  - N-acetyltransferase genotypes in the Portuguese population.
AB  - Fast and slow acetylator phenotypes differ in their respective frequencies among
      different populations. A polymerase chain reaction-restriction fragment length
      polymorphism based genotyping assay was used to determine the frequency of the
      most important NAT2 polymorphisms in a group of 128 Portuguese individuals. The
      results showed that slow acetylators represented 64.1% of the group, and the
      frequencies of NAT2*4, *5A, *5B, *5C, *6 and *7 alleles were 0.211, 0.031, 0.379,
      0.023, 0.328 and 0.027, respectively. These values are similar to those presented
      in other studies in Caucasians. The data obtained may be useful in
      epidemiological studies of the influence of acetylator polymorphisms on
      carcinogenesis or other environmental caused diseases.

PMID- 9918141
TI  - Relevance of deficient CYP2D6 in opiate dependence.

PMID- 9918142
TI  - Instability-induced osteoarthritis in the metacarpophalangeal joint of horses.
AB  - OBJECTIVE: To establish an instability model of osteoarthritis (OA) that mimics
      the early changes of naturally acquired OA. ANIMALS: 6 mature radiographically
      normal horses. Procedure-The collateral and lateral collateral sesamoidean
      ligaments were transected in a metacarpophalangeal (MCP) joint in each horse.
      Lameness examinations were performed every 7 days after surgery for 8 weeks.
      Radiographs were taken immediately before and after desmotomy and 8 weeks after
      surgery. Eight weeks after surgery, bilateral MCP joints were grossly evaluated,
      specimens of articular cartilage were harvested for histologic examination and
      tissue culture, and synovial membrane was harvested for histologic examination.
      RESULTS: Lameness scores significantly increased over time (mean score of 1.6 for
      the 8-week study period). Joint circumference was significantly greater and range
      of motion significantly less in OA joints, compared with contralateral joints.
      Number and size of osteophytes were significantly greater in OA joints. Amount of
      newly synthesized proteoglycan (PG) was significantly greater at 18 and 72 hours
      of cartilage explant culture for OA joints, compared with contralateral joints.
      Total PG content and PG degradation did not differ between OA and contralateral
      joints. IMPLICATIONS FOR HUMAN MEDICINE: This instability model in horses may be
      useful in the study of OA in humans. CONCLUSION: Desmotomy of the lateral
      collateral and lateral collateral sesamoidean ligaments induced instability
      similar to that of naturally acquired OA in horses, as documented by lameness,
      clinical signs of OA, osteophyte formation, and erosions of articular cartilage
      surfaces and score lines in OA joints.

PMID- 9918143
TI  - Hemodynamic effects of thyroidectomy in sedentary horses.
AB  - OBJECTIVE: To investigate hemodynamic effects of thyroidectomy in horses at rest.
      ANIMALS: 6 healthy aged Quarter Horse mares. PROCEDURE: Horses were monitored for
      5 months before and 4 weeks after thyroidectomy and for an additional 4 weeks
      after administration of thyroid hormone supplement (2.5 microg of thyroxine/kg of
      body weight, PO, q 12 h, and 0.6 microg of triiodothyronine/kg, PO, q 12 h).
      Responses to thyroid-stimulating hormone (TSH) were measured before and 4 weeks
      after thyroidectomy. Other variables monitored daily were resting rectal
      temperature (T), heart rate (HR), respiratory rate (RR), and body weight (BW).
      Monthly cardiac output (Q), blood volume (BV), plasma volume (PV), standard
      electrocardiographic measures, systolic and right ventricular blood pressure, and
      HR responses were determined after IV administration of isoproterenol and
      phenylephrine. Variables were analyzed by use of repeated-measures ANOVA.
      RESULTS: Complete thyroidectomy was confirmed by minimal response to TSH 4 weeks
      after surgery. Resting HR, RR, T, Q, and beta-adrenergic responsiveness to
      isoproterenol decreased significantly after thyroidectomy. Resting T, Q, and beta
      adrenergic responsiveness increased after administration of supplement and was
      not significantly different from euthyroid values. Blood volume and PV increased
      significantly after thyroidectomy but did not return to euthyroid values despite
      administration of supplement. Response to phenylephrine was minimally different
      between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Thyroidectomy in horses
      caused decreased resting HR, RR, T, Q, and isoproterenol responsiveness and
      increased BV, PV, PQ interval, and QT interval corrected for HR. Some of these
      surgically induced changes appeared to be partially reversed by administration of
      thyroid hormone supplement.

PMID- 9918144
TI  - Effect of timing and route of administration of furosemide on pulmonary
      hemorrhage and pulmonary arterial pressure in exercising thoroughbred racehorses.
AB  - OBJECTIVES: To examine effect of pre-exercise administration of furosemide (FUR)
      on mean pulmonary arterial pressure (PAP) during work and RBC concentration in
      bronchoalveolar lavage fluid (BALF) collected 40 minutes after exercise. ANIMALS:
      10 adult Thoroughbreds. PROCEDURE: A modified 10 X 10 crossover design comprising
      10 horses during 10 weeks was used. Each horse received each of 5 treatments
      twice. Treatment structure included a control plus a 2 X 2 factorial and
      consisted of the following: A, control; B, FUR, 250 mg, IV, 30 minutes before
      exercise; C, FUR, 250 mg, IV, 240 minutes before exercise; D, FUR, 250 mg,
      nebulized, 30 minutes before exercise; and E, FUR, 250 mg, nebulized, 240 minutes
      before exercise. Mean PAP data were collected, and each horse, after a 500-m warm
      up, was galloped at maximal speed for 1,600 m. BALF RBC concentration was
      determined by hemocytometer. RESULTS: Interaction between treatment method and
      time of administration was significant (P = 0.04). Treatment B resulted in
      significantly (P = 0.01) lower BALF RBC concentration than did treatment C. Only
      BALF RBC count after treatment B was significantly lower than the control value.
      Horses that received FUR IV had significantly lower peak mean PAP than did those
      that received the drug by nebulization, regardless of administration time. Only
      treatment B resulted in peak mean PAP that was significantly lower than that of
      control. Exercise time was not influenced by treatment. CONCLUSIONS: FUR,
      administered IV 30 minutes before exercise, significantly reduced peak mean PAP
      and BALF RBC concentration.

PMID- 9918145
TI  - Urolithiasis in dogs V: regional comparisons of breed, age, sex, anatomic
      location, and mineral type of calculus.
AB  - OBJECTIVE: To determine extent and nature of regional differences in distribution
      of canine urinary calculi. SAMPLE POPULATION: 13,552 calculus specimens: 7,056
      (52.1%) from females, 6,492 (47.9%) from males, and 4 from dogs of unrecorded
      sex. Procedure Records were used to compile information from all specimens
      submitted between July 1981 and December 1995. Results from mixed-breed and
      various breeds of stone-forming dogs were analyzed. Interrelations of breed, sex,
      and age of dogs, and anatomic location and mineral composition of specimens were
      analyzed and compared for 6 US geographic regions. RESULTS: Struvite-, apatite-,
      and urate-containing calculi were reported significantly most often from female
      dogs of the Mountain/Pacific region. Oxalate-, silica-, and brushite-containing
      calculi were reported significantly most often from male dogs in the New
      England/mid-Atlantic (NEMA) region. Cystine-containing calculi were reported most
      frequently from the NEMA and South Central (SC) regions. Dogs from the NEMA
      region were oldest in average age at diagnosis. Significant regional differences
      in distribution were found for several breeds. Sex distribution of renal calculi
      in 11 breeds of dogs (Lhasa Apso, Yorkshire Terrier, Shih Tzu, Basset Hound, Pug,
      Mastiff, Bichon Frise, Doberman Pinscher, Dalmatian, English Bulldog, and
      Pekingese) reported to be at high risk of renal lithiasis differed among the 6
      geographic regions. Renal and ureteral calculi were reported significantly most
      often from dogs in the South Atlantic region, and bladder and urethral calculi
      were reported most often from dogs in the SC region. CONCLUSIONS: Wide regional
      differences exist in distribution of stone-forming dogs by sex, average age at
      diagnosis, breed, and minerals contained within and anatomic location of calculi.

PMID- 9918146
TI  - Potential for contact and mechanical vector transmission of vesicular stomatitis
      virus New Jersey in pigs.
AB  - OBJECTIVE: To determine whether swine could be infected with vesicular stomatitis
      virus New Jersey (VSV-NJ) by routes simulating mechanical vector and contact
      transmission, and to document clinical response and measure source, duration, and
      extent of associated viral shedding. ANIMALS: 48 approximately 10-kg male pigs.
      PROCEDURE: 7 inoculation routes were tested at 3 virus concentrations (10(6),
      10(4), and 10(2) median tissue culture-infective doses [TCID50]). Inoculation
      routes included intradermal (snout), topical application of virus to a scarified
      area (ear or mucous membrane of the lip), mucosal (oral or conjunctiva)
      application, and nasal instillation (drop or aerosol). Swine were monitored daily
      for clinical disease, seroconversion, and virus isolation. RESULTS: Virus was
      isolated from swab specimens of nasal planum, nasal cavity, saliva, tonsil, and
      feces from 15 pigs infected by intradermal snout inoculation (10(6) and 10(4)
      TCID50), scarification of the lip (10(6) and 10(4) TCID50), and oral route (10(6)
      TCID50). Virus was not isolated from plasma. Vesicular lesions were restricted to
      pigs inoculated via intradermal snout and lip scarification routes.
      Seroconversion was detected in 23 pigs inoculated by all routes except intranasal
      aerosol and conjunctival. Frequency of virus isolation from these pigs was
      dependent on serologic status and presence of vesicular lesions. CONCLUSIONS:
      Viral titers obtained from swab specimens and infective doses indicated that
      sufficient virus is shed from infected swine for contact or mechanical
      transmission to occur. Amount of virus is highest when lesions are present and
      before seroconversion. Pigs may represent an effective large-animal model for
      studying pathogenesis and transmission of VSV-NJ.

PMID- 9918147
TI  - Morphologic comparisons among equine endometrium categories I, II, and III, using
      light and transmission electron microscopy.
AB  - OBJECTIVE: To evaluate whether the pathologic changes observed by light
      microscopy in endometrium of categories II and III were reflected by cellular
      changes and to describe differences in the endometrial cell ultrastructure during
      estrus and diestrus. ANIMALS: 18 healthy mares. PROCEDURE: Endometrial tissues
      biopsied during the physiologic breeding season were categorized, using light
      microscopy, and were studied, using transmission electron microscopy (TEM).
      RESULTS: Using TEM, glycogen granules were associated with giant mitochondria for
      all endometrial types during diestrus. Development of rough endoplasmic reticulum
      (RER) and Golgi apparatus suggested protein synthesis in the endometrial glands
      during diestrus. TEM did not reveal major ultrastructural differences, between
      endometrium of categories I and II. This was unlike differences identified by
      light microscopy. The most extensive pathologic changes were seen in category-III
      tissue (TEM and light microscopy). Category-III endometria had a large number of
      light cells with more degenerative structures and fewer organelles, and lacked
      cilia in the lumen of the glands. This tissue had extensive fibrotic tissue in
      the lamina propria and many inflammatory cells in most tissue layers.
      CONCLUSIONS: The severe ultrastructural changes may be one of the many factors
      decreasing the fertility of mares with category-III, compared with category-1 and
      -2, endometrium.

PMID- 9918148
TI  - Permanent implantation of a reinforced polytetrafluoroethylene vascular graft for
      treatment of artificial defects of the teat cistern mucosa in cows.
AB  - OBJECTIVE: To evaluate use of a reinforced polytetrafluoroethylene vascular graft
      for treatment of an artificial defect of mucosa of the teat cistern in lactating
      cows. DESIGN: Prospective study. ANIMALS: 9 clinically normal lactating dairy
      cows. PROCEDURE: A 20-mm wide circumferential area of mucosa was sharply excised
      from the cistern of 1 teat on each cow 10 days after spontaneous calving, and the
      lesion was covered by a graft. After 14 days of passive milk drainage, routine
      milking was resumed. Follow-up examinations were performed during the next 2
      lactation periods and included evaluation of wound healing, location and
      sonographic appearance of the implant, milk flow and yield, and somatic cell
      counts. Cows were slaughtered, and teats and mammary glands were examined
      microscopically. RESULTS: Implants had partially to totally collapsed within 30
      to 90 days. Milk flow was significantly increased by day 15 of the first
      lactation, but decreased significantly by day 300 of lactation 1. At the end of
      lactation 1, milk flow had ceased in 3 out of 7 quarters. Only 3 of 9 quarters
      drained through grafted teats were milkable at the end of the study. Somatic cell
      counts of these quarters were significantly increased in the first lactation
      period. At necropsy, 2 grafts were in the teat cistern, but only 1 was
      incorporated into the mucosa by connective tissue. The mucosa was thickened in
      all teats with grafts, and there was epithelial metaplasia and granulation tissue
      proliferation. CLINICAL RELEVANCE: Use of a polytetrafluoroethylene graft can
      preserve patency in the first lactation period. However, the graft may not be
      sufficiently incorporated into the mucosa if routine machine milking is resumed 2
      weeks after implantation. )

PMID- 9918149
TI  - Effect of various short-term storage methods on viability of cancellous bone
      fragments.
AB  - OBJECTIVE: To determine effects of various storage methods on ex vivo viability
      of cancellous bone fragments. SAMPLE POPULATION: Cancellous bone fragments
      obtained from 4 New Zealand White rabbits. PROCEDURE: Cancellous bone fragments
      were stored for 3 hours on ice in 1 of 5 preservation solutions or in 0.9% NaCl.
      Fragments were then reperfused (37 C) in oxygenated physiologic buffer solution
      for 1 hour. Cellular viability in fragments was assessed by ethidium monoazide
      labeling and fluorescence microscopy. RESULTS: Viability in fresh cancellous bone
      ranged from 85 to 100% (mean+/-SEM, 88+/-7%). Storage of fragments significantly
      reduced viability. Viability in bone fragments stored at 22 C in blood-soaked
      sponges or 0.9% NaCl solution was 63.8+/-3 and 65.2+/-7%, respectively. Use of
      cold 0.9% NaCI solution reduced viability to 53.6+/-3%. Viability was
      significantly better for fragments stored in cold phosphate-buffered sucrose
      (70.4+/-2%) and EuroCollins (71.4+/-3%) solutions. After warm reperfusion,
      viability was best for fragments stored in cold phosphate-buffered sucrose
      (70.2+/-4%), EuroCollins (72.6+/-3%), or UW lactobionate solutions (69.6+/-3%),
      compared with those stored in cold 0.9% NaCl (47.6+/-3%) or hypertonic citrate
      (53.0+/-3%) solutions or blood-soaked sponges (57.2+/-3%). CONCLUSIONS:
      Hypothermic storage in solutions designed to prevent temperature-dependent cell
      injury were best for maintaining cancellous bone fragment viability. CLINICAL
      RELEVANCE: Hypothermia may be advantageous for use in storing cancellous bone
      fragments during procedures that dictate a prolonged period between harvest and
      placement of graft fragments.

PMID- 9918150
TI  - Effect of a conjugate of polymyxin B-dextran 70 in horses with experimentally
      induced endotoxemia.
AB  - OBJECTIVE: To determine the efficacy of polymyxin B-dextran 70 (PBD) for
      treatment of endotoxemic horses. ANIMALS: 15 horses during study 1 and 6 horses
      during study 2. PROCEDURES: 3 groups were used in study 1. Horses in groups 1 and
      2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60
      minutes. Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15
      minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and
      3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were
      obtained for hemograms and determination of cytokine, lactate, and prostanoid
      concentrations. In study 2, horses were given ketoprofen (2.2 mg/kg) or saline
      solution 15 minutes before infusion of PBD. Fourteen days later, treatments were
      reversed, using a crossover design. Blood samples were obtained for measurement
      of thromboxane B2 (TXB2) concentration. RESULTS: For study 1, prior treatment
      with PBD completely blocked endotoxin-induced changes for heart and respiratory
      rates, rectal temperature, WBC count, and plasma tumor necrosis factor,
      interleukin 6, TXB2, and prostaglandin F1 concentrations. There was transient
      tachypnea, sweating, and increased plasma TXB2 concentration in horses given PBD
      (with or without LPS). Prior treatment with ketoprofen eliminated all PBD-induced
      signs and prevented the increase in plasma TXB2 concentration. CONCLUSIONS: Signs
      of endotoxemia were prevented in horses by treatment with PBD, although its use
      was associated with mild adverse effects. CLINICAL RELEVANCE: When used in
      combination with a cyclooxygenase-inhibiting drug, PBD has potential for
      treatment of horses with endotoxemia.

PMID- 9918151
TI  - Effect of coat on rate of temperature increase in muscle during ultrasound
      treatment of dogs.
AB  - OBJECTIVE: To determine effect of coat during ultrasound treatment and to
      establish a protocol to achieve adequate thermal effects. ANIMALS: 9 healthy
      adult dogs. PROCEDURE: A standardized area was treated on the semitendinosus
      muscle of sedated dogs. Needle thermistors were inserted in the biceps femoris
      muscle to depths of 5 and 10 cm and in the ultrasound gel in the treatment area.
      Each dog was given 4 randomized 10-minute treatments (intensities of 0.5, 1.0,
      1.5, and 2.0 W/cm2). Temperatures were measured at 30-second intervals during
      treatment and at 1- to 2-minute intervals after treatment. RESULTS: Baseline
      temperatures (mean+/-SD) were 30.6+/-1.8 C for coat, 38.2+/-1.2 C at a depth of 5
      cm, and 39.0+/-0.7 C at a depth of 10 cm. At the 5-cm depth, an increase of > 1.6
      C was obtained only with the maximum intensity when coat was clipped. Treatment
      with maximum intensity through short and long coats yielded mean increases at a
      depth of 5 cm of 0.7 and 0.4 C, respectively. Temperature at the 10-cm depth
      increased < 0.6 C for all treatments. Temperatures within the coat increased
      approximately 8.3 C and 22.2 C for short and long coats, respectively, with
      intensities of 1.5 and 2.0 W/cm2. CONCLUSIONS: Ultrasound treatment applied
      through an intact coat considerably warmed the coat with loss of thermal effects
      in underlying tissues. Inappropriate heating was apparently affected by selection
      of intensity, duration, and size of treatment area. CLINICAL RELEVANCE: Coat can
      impede successful use of ultrasound treatment of dogs.

PMID- 9918152
TI  - Protective role of maternal antibodies against Haemophilus parasuis infection.
AB  - OBJECTIVE: To evaluate the impact of maternal antibodies after challenge exposure
      of baby pigs with a homologous serovar of Haemophilus parasuis. ANIMALS: 7 gilts
      and their litters from a high health status farm. PROCEDURE: Gilts were
      vaccinated twice with a commercial bacterin that contained H parasuis serovar 4
      and 5 or, as a control, adjuvant only. A group of pigs was also vaccinated
      similarly before challenge exposure. After early and late challenge exposure at 3
      and 4 weeks, respectively, all pigs from vaccinated gilts were evaluated for
      clinical signs of infection, lesions, and antibody titer. RESULTS: All pigs
      coming from control gilts had severe signs of H parasuis infection. Macroscopic
      lesions included polyserositis and pneumonia, and bacteriologic examination
      confirmed H parasuis as the etiologic agent. Vaccinated pigs born to vaccinated
      gilts did not have clinical signs of disease. However, some vaccinated pigs born
      to control gilts had signs of nervous system dysfunction and lameness. There was
      no difference in lesion scores between early or late challenge exposure, but
      lesions scores for pigs from vaccinated and control gilts were different (P <
      0.01). CONCLUSIONS: Under these experimental conditions, immune-naive and
      vaccinated pigs from vaccinated gilts were protected against systemic lesions
      when challenge exposed with a virulent strain of H parasuis. CLINICAL RELEVANCE:
      Vaccination of the gilt and pigs protects the latter from polyserositis, but
      results are not different from those for nonvaccinated pigs from vaccinated
      gilts. Maternal antibodies did not seem to interfere with vaccination of pigs at
      1 and 3 weeks of age.

PMID- 9918154
TI  - Influence of sex and age on serum total immunoglobulin E concentration in
      Beagles.
AB  - OBJECTIVE: To establish an ELISA for detection of serum total IgE concentration
      in dogs and to analyze IgE values in a dog colony. ANIMALS: 147 healthy Beagles
      (31 males and 116 females). PROCEDURE: 2 canine IgE-specific polyclonal
      antibodies elicited by 2 recombinant fragments of the epsilon chain in hens were
      used to develop a capture ELISA specific for serum total IgE concentration. The
      IgE values were calculated by comparing serum dose-response curves (1:50 to
      1:6,400) with a reference serum pool assigned 100 relative ELISA units (REU).
      Results-Mean IgE concentration in female Beagles was 51.2 REU (range, 0 to 337.8
      REU; median, 31.4 REU), whereas mean IgE concentration in male dogs was only 7.5
      REU (range, 0 to 32.6 REU; mean, 3.6 REU). Distribution of IgE values was skewed;
      approximately 80% of dogs had IgE values < 50 REU. Analysis of natural
      logarithmically transformed IgE values indicated that sex and age significantly
      (P < 0.05) influenced IgE values; mean serum IgE values increased until the age
      of 4 years. Heritability estimates of IgE concentration indicated a trend toward
      a genetic influence. CONCLUSION: A reliable capture ELISA specific for canine IgE
      was developed. Serum total IgE values vary with age and sex in the sample
      population. CLINICAL RELEVANCE: Serum total IgE concentration can now be
      evaluated in various dog breeds and, subsequently, in dogs with IgE-mediated
      diseases provided that these significant influences are accounted for. Serum
      total IgE values may then prove to be of diagnostic value, similar to their use
      in human beings.

PMID- 9918153
TI  - Changes in rectal temperature and hematologic, biochemical, blood gas, and acid
      base values in healthy Labrador Retrievers before and after strenuous exercise.
AB  - OBJECTIVE: To measure changes in rectal temperature and hematologic, biochemical,
      blood gas, and acid-base values before and after exercise. ANIMALS: 14 healthy
      adult Labrador Retrievers. PROCEDURE: Dogs exercised continuously for 10 minutes
      by repeatedly retrieving a dummy thrown approximately 40 to 50 yards on land. The
      ambient temperature during each exercise period was recorded. Rectal temperature,
      pulse, and respiratory rate were measured; CBC and serum biochemical profile were
      determined; and arterial blood gas tensions, acid-base status, and plasma lactate
      and pyruvate concentrations were measured at rest and immediately after exercise.
      Rectal temperature, pulse, respiratory rate, and lactate and pyruvate
      concentrations were evaluated at intervals up to 120 minutes after exercise.
      RESULTS: Immediately after exercise, rectal temperature increased markedly;
      ambient temperature did not affect rectal temperature. Arterial blood pH and PaO2
      were significantly increased after exercise, and PaCO2 and bicarbonate
      concentration were significantly decreased after exercise. Also, statistically,
      but not clinically, significant increases were observed in RBC, WBC, and
      segmented neutrophil counts; hemoglobin, total protein, and serum sodium and
      potassium concentrations; PCV; anion gap; and creatine kinase activity. Plasma
      lactate and pyruvate concentrations increased significantly after exercise, but
      there was no change in the lactate-to-pyruvate ratio. CONCLUSION AND CLINICAL
      RELEVANCE: Reference values for healthy Laborador Retrievers during a
      standardized exercise protocol were established to compare data obtained from
      Laborador Retrievers with exercise intolerance and collapse. Important
      characteristics of lactate and pyruvate metabolism were documented that will
      enable more precise evaluation of exercise intolerance in this breed.

PMID- 9918155
TI  - Effects of R and S enantiomers and a racemic mixture of carprofen on the
      production and release of proteoglycan and prostaglandin E2 from equine
      chondrocytes and cartilage explants.
AB  - OBJECTIVE: To examine effects of carprofen (enantiomers and a racemic mixture) on
      the metabolism of equine chondrocytes. SAMPLE POPULATION: Cartilage from
      clinically normal horses. PROCEDURE: Effects of carprofen on proteoglycan
      neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2
      production by unstimulated chondrocyte monolayers and cartilage explants were
      examined, as were similar variables in monolayers and explants exposed to
      carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers
      and racemic mixture) was used alone or along with IL-1 on monolayers and explant
      cultures. Medium was collected 48 to 96 hours later, and cartilage was digested.
      Proteoglycan synthesis was assessed as the amount of 35S-labeled proteoglycan in
      medium and digested cartilage. Total GAG content of the medium and digested
      cartilage was measured, and proteoglycan degradation was calculated.
      Radioimmunoassay was used to measure PGE2 production. RESULTS: Carprofen
      significantly decreased PGE2 production by unstimulated chondrocytes and
      antagonized an IL-1-induced increase in PGE2 production. Carprofen significantly
      increased proteoglycan synthesis in unstimulated monolayers and explants.
      Concurrently, there was a decrease in GAG release by explants. Use of IL-1
      significantly decreased proteoglycan synthesis, but the highest concentrations of
      carprofen partially reversed this effect in chondrocyte monolayers. CONCLUSIONS:
      Carprofen had a potentially beneficial effect on proteoglycan metabolism of
      equine chondrocytes. This effect was sufficiently strong at the highest
      concentrations to overcome inhibitory effects of IL-1 on proteoglycan synthesis.
      Carprofen also inhibited PGE2 production by unstimulated and IL-1-stimulated
      chondrocytes. Carprofen induced these enantiomer-specific effects. CLINICAL
      RELEVANCE: Use of carprofen in osteoarthritic horses may induce beneficial
      changes in articular cartilage matrix.

PMID- 9918156
TI  - Anatomic and surgical approach to the ethmoidal nerve and parasympathetic
      innervation of the nasal and cerebral circulation in sheep.
AB  - OBJECTIVE: To describe an anatomic and surgical approach to the efferent
      parasympathetic branches of the pterygopalatine ganglia in sheep, with particular
      reference to the ethmoidal nerve and innervation of nasal and cerebral blood
      vessels. ANIMALS: 12 adult sheep used for monolateral (n = 7) or bilateral (n =
      5) ethmoidal neurectomy; 2 sheep used for angiography (1 live sheep for digital
      subtraction angiography, 1 embalmed cadaver for injection studies); and 5
      embalmed cadavers, 4 frozen specimens, and 2 dry skulls used for dissection, x
      rays, and computed tomographic (CT) or magnetic resonance (MR) scans. PROCEDURE:
      Transverse (coronal) MR scans, transverse, sagittal, and dorsal CT scans,
      radiography, angiography, photographic images, and dissections of embalmed
      material were used to study the topographic anatomy of the temporal and
      pterygopalatine fossae of the head. RESULTS: Images were stored, then compared
      with photographs of frozen sections from the same or a similar specimen to plan a
      surgical approach to the ethmoidal nerve. Mono- and bilateral experimental
      ethmoidal neurectomies were performed, allowing characterization of a safe and
      reliable method. The series of pterygopalatine ganglia typical of this species
      was localized, dissected, and analyzed for topographic relations. CONCLUSIONS:
      From the results, a new approach to the efferent branches of the pterygopalatine
      ganglia (ethmoidal nerve) for experimental parasympathectomy of the cerebral and
      nasal circle is proposed. This experimental approach could be used for studies
      involving thermoregulation of the face, and in experimental control of blood flow
      in the nasal cavity and rostral part of the brain.

PMID- 9918157
TI  - Plasma amino acid profiles in cats with naturally acquired chronic renal failure.
AB  - OBJECTIVE: To characterize potential changes in preprandial plasma amino acid
      concentrations in cats with naturally acquired chronic renal failure (CRF),
      compared with healthy cats, and to assess potential effects of the severity of
      renal failure on plasma amino acid concentrations in these cats. ANIMALS: 62
      adult cats. PROCEDURE: Preprandial plasma amino acid concentrations were
      evaluated in 38 cats with mild, moderate, or severe CRF and in 24 apparently
      healthy cats. Effects of severity of renal failure, amount of dietary protein,
      degree of weight loss, appetite, and body condition on plasma amino acid profiles
      were evaluated. RESULTS: Cats with various stages of CRF had significantly (P<
      0.05) decreased plasma concentrations of o-hydroxyproline, glutamate, proline,
      glycine, alanine, tyrosine, tryptophan, and arginine, and significantly increased
      plasma concentrations of asparagine, citrulline, ornithine, 1-methylhistidine,
      and 3-methylhistidine. Significant (P < 0.05) alterations in amino acid
      concentrations also were identified when cats with CRF were grouped by appetite
      or severity of renal disease. Amount of dietary protein, body condition, or
      degree of weight loss had no significant effect on plasma amino acid
      concentrations. CONCLUSIONS: Compared with those in healthy cats, preprandial
      plasma amino acid profiles in cats with mild, moderate, or severe CRF are
      abnormal. CLINICAL RELEVANCE: Despite frequency of altered plasma amino acid
      concentrations in cats with CRF, the magnitude of these changes is mild and of
      little clinical relevance. Short-term use of a commercial protein-restricted diet
      has no deleterious effects on plasma amino acid concentrations.

PMID- 9918158
TI  - Purification of two equine pepsinogens by use of high-performance liquid
      chromatography.
AB  - OBJECTIVES: To purify and characterize pepsinogens in equine gastric mucosa.
      SAMPLE POPULATION: Stomachs collected from 2 healthy horses at necropsy.
      PROCEDURE: After collection, stomachs were placed immediately in ice before
      storage at -48 C. After slow thawing, the mucosa was scraped off while the tissue
      was immersed in 0.1M potassium phosphate (pH 7.4) at 4 C, then was homogenized.
      The filtered extract was subjected to anion-exchange chromatography. Fractions
      that were found to contain pepsin or pepsinogen were further chromatographed.
      Individual fractions were tested for pepsinogen or pepsin content by monitoring
      proteolytic activity at pH 2 and 3, respectively. Fractions from all columns were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to confirm
      molecular weight of pepsinogens and pepsin. RESULTS: Two pepsinogens and at least
      1 pepsin were purified from equine gastric mucosa. CONCLUSIONS: On the basis of
      molecular mass, equine gastric mucosa contains 2 pepsinogens. CLINICAL RELEVANCE:
      Results of this study will enable future development of an ELISA or
      radioimmunoassay for use in the diagnosis of equine gastric ulceration.

PMID- 9918159
TI  - Diagnostic implications of concurrent inoculation with attenuated and virulent
      strains of porcine reproductive and respiratory syndrome virus.
AB  - OBJECTIVE: To determine the predominant strain of progeny virus in samples
      obtained from cell cultures and pigs exposed simultaneously to attenuated and
      virulent strains of porcine reproductive and respiratory syndrome virus (PRRSV).
      SAMPLE POPULATION: Cell cultures and twenty 4-week-old pigs. PROCEDURE: Cell
      cultures and pigs were simultaneously exposed to various relative concentrations
      of an attenuated, cell-culture-adapted vaccine strain and a virulent field strain
      of PRRSV. Progeny virus obtained at selected intervals thereafter was tested to
      determine strain identity by use of restriction fragment length polymorphism
      (RFLP) analysis. RESULTS: Progeny virus from infected cell cultures comprised the
      attenuated strain, alone or in combination with the virulent strain, except when
      cultures had been exposed to a large excess (> 100,000-fold) of the virulent
      strain. Progeny virus from infected pigs comprised only the virulent strain
      regardless of the relative concentrations of the 2 strains to which the pigs had
      been exposed. CONCLUSIONS: During concurrent replication in cell cultures, the
      attenuated strain quickly predominated. Conversely, during concurrent replication
      in pigs, the virulent strain quickly predominated. CLINICAL RELEVANCE: It is
      unlikely that only an attenuated strain of PRRSV would be identified by RFLP
      testing of samples obtained from pigs concurrently infected with a virulent
      strain of PRRSV. Nevertheless, the ability of a cell-culture-adapted attenuated
      strain of PRRSV to predominate during cell culture passage (the first step in the
      current RFLP testing procedure) indicated that, if possible, samples should be
      obtained from pigs that do not have a history of direct or indirect exposure to
      attenuated-virus vaccine.

PMID- 9918161
TI  - Culture and characterization of equine terminal arch endothelial cells and hoof
      keratinocytes.
AB  - OBJECTIVES: To develop methods to isolate, culture, and characterize equine hoof
      endothelial cells (EC) and keratinocytes. SAMPLE POPULATION: Cells harvested from
      the forelimbs of 8 horses. PROCEDURE: EC were obtained via catheters placed in
      the palmar digital arteries of the disarticulated lower portion of the forelimbs
      from 4 horses that had been heparinized prior to euthanasia. Phosphate-buffered
      saline solution was used to remove and discard RBC from blood vessels, and
      collagenase was used to loosen and flush EC from the vasculature. Hoof
      keratinocytes were obtained from 4 recently euthanatized horses by use of
      dispase/trypsin dissociation of the coronary band epidermis. Use of an
      extracellular matrix gel as a culture flask attachment factor was important to
      the success of hoof keratinocyte cultures. RESULTS: EC from the palmar digital
      arteries were successfully cultured and characterized by in vitro morphology,
      uptake of a fluorescence-labeled acetylated-low density lipoprotein, and lack of
      expression of von Willebrand factor and smooth muscle actin. Hoof keratinocytes
      were characterized by morphology in culture and expression of keratin proteins,
      as determined by immunochemical reaction. Keratinocyte cultures were also
      positive for vimentin expression. CONCLUSIONS: Culture techniques to isolate and
      characterize hoof cells should aid investigators in their study of equine hoof
      pathobiologic features, especially as it relates to laminitis.

PMID- 9918160
TI  - Relation between pathologic findings and cellular immune responses in sheep with
      naturally acquired paratuberculosis.
AB  - OBJECTIVE: To investigate the relation between lesions and cellular immune
      response-based tests in sheep with naturally acquired paratuberculosis and to
      evaluate efficacy of an interferon-gamma (IFN-gamma) assay and the intradermal
      skin test. ANIMALS: 110 and 88 adult sheep were used to evaluate the IFN-gamma
      assay and skin test, respectively. PROCEDURE: Before euthanasia, heparinized
      blood was collected and incubated with avian purified protein derivative (PPD).
      Interferon-y production was assessed, using a commercial enzyme immunoassay. Skin
      testing in the caudal fold also was performed, using avian PPD. Sensitivity and
      specificity of these techniques were evaluated, using histopathologic findings as
      reference. RESULTS: Of the sheep examined, 61 (55.4%) had lesions that were
      classified in 5 categories, according to location, extension, cellular types, and
      presence of acid-fast bacilli. Regarding cellular immunity test results, 55.4% of
      sheep with and 6.1 % without pathologic changes had positive results of the IFN
      gamma assay. Skin test sensitivity (55.6%) and specificity (100%) were slightly
      greater. CONCLUSION: Close association between pathologic findings and cellular
      immune response was apparent. Most sheep with focal (tuberculoid) and some with
      diffuse lesions (borderline tuberculoid), all with scant or no acid-fast bacilli
      in the intestine, had positive results of the IFN-gamma assay and skin test. Most
      sheep with diffuse lesions and high numbers of bacilli (borderline lepromatous)
      were test negative. CLINICAL RELEVANCE: Cellular immune response-based and
      serologic tests are useful tools for seeking evidence of paratuberculosis. Each
      technique detects different types of immune-reacting sheep, and their
      simultaneous use may detect most infected animals.

PMID- 9918162
TI  - Progress in congenital hearing loss.

PMID- 9918163
TI  - Cochlear implants in the Third Millennium.

PMID- 9918164
TI  - Complications of otitis media: the importance of early recognition.
AB  - OBJECTIVE: The purpose of this study was to determine the factors that are
      important for the early diagnosis of intracranial and intratemporal complications
      of otitis media. STUDY DESIGN: The study design was a retrospective follow-up
      study. SETTING: The study took place at a tertiary referral center. PATIENTS: The
      medical history of 23 patients with intracranial and intratemporal complications
      of otitis media was analyzed. INTERVENTIONS: Diagnostic and therapeutic
      procedures were performed. MAIN OUTCOME MEASURES: Age, initial diagnosis, final
      diagnosis, early presenting symptoms, otoscopic findings, time interval between
      the first manifestation of symptoms and the start of therapy, and follow-up
      status were measured. RESULTS: In almost all patients, early symptoms included
      persisting fever and headache. High morbidity and mortality were correlated to a
      prolonged time interval between the early symptomatology and start of treatment.
      Doctor's delay was regarded as the most significant delaying factor. CONCLUSION:
      Early diagnosis of otogenic complications of otitis media based on the early
      symptoms persisting fever and headache can reduce morbidity and mortality
      associated with these complications.

PMID- 9918165
TI  - Morphologic and biologic changes of experimentally induced cholesteatoma in
      Mongolian gerbils with anticytokeratin and lectin study.
AB  - HYPOTHESIS: Aural cholesteatoma has different morphologic and biologic
      characteristics from the normal epithelial cells. BACKGROUND: The exact
      pathophysiology of aural cholesteatoma has not been proved. There are certain
      factors that can be involved in the development of the aural cholesteatoma, which
      makes it necessary to find the morphologic and biologic changes in aural
      cholesteatoma. METHODS: The animal model of aural cholesteatoma was induced in
      gerbils with the external auditory canal (EAC) ligation method. Using
      immunohistochemical method, the distribution of cytokeratin and the binding
      patterns of lectin were observed to show the biologic and morphologic changes
      that take place in aural cholesteatomas. RESULTS: The successful induction rate
      was 86.7%. The cytokeratin distribution of aural cholesteatoma was similar to
      that of EAC but different from that of the middle ear mucosa. The cytokeratin
      distribution in the cholesteatoma did not change with the different duration of
      EAC ligation. The results of the lectin-binding study indicate that the mucin
      type cells are mainly distributed in the suprabasal cells of aural cholesteatoma
      and that the basal cells of cholesteatoma lack a D-galactosyl sugar residue.
      CONCLUSION: This study suggests that the origin of aural cholesteatoma may be the
      external auditory canal epidermal cells, and the characteristics of these cells
      do not change once the cholesteatoma develops. This study also suggests that
      cholesteatoma has different biologic nature from that of the normal epithelial
      cell, especially in the basal cells.

PMID- 9918166
TI  - Malleus-handle fracture: historical review and three new cases.
AB  - OBJECTIVE: Isolated malleus-handle fracture is a clinical entity seldom reported
      in the medical literature but well known in the last century. The purpose of this
      paper was to review the literature over the last 150 years and describe three new
      cases. STUDY DESIGN: Extensive review of the literature and chart review of three
      patients with isolated malleus-handle fracture. SETTING: The study was performed
      partly at a private practice and partly in an academic tertiary referral center.
      PATIENTS: At least 43 malleus-handle fractures have been reported in the
      literature. Three new occurrences were studied. RESULTS: The review of the
      literature showed that head trauma with skull base fracture was the most frequent
      cause of malleus-handle fracture, followed by blows on the tympanic membrane and
      barotrauma, penetration of pen-holders or hair pins, penetration of twigs, and
      attempts to remove a foreign body pushed inside the ear. In the first patient
      reported here, the malleus-handle fracture was caused by a whirlpool bath, in the
      second, the cause was unknown, and, in the third, it was caused by a brisk
      decompression inside the ear canal. CONCLUSIONS: This lesion is not rare, and the
      diagnosis frequently is missed because the tympanic membrane appears intact. A
      careful otoscopic examination with pneumomassage, an abnormally high compliance
      at tympanometry, and a carefully recorded medical history may lead to the
      diagnosis of isolated malleus-handle fracture in a patient with a mild conductive
      hearing loss.

PMID- 9918167
TI  - Delayed facial palsy after tympanomastoid surgery.
AB  - OBJECTIVES: The purpose of this report is to provide data on the incidence of
      delayed facial palsy (DFP) after tympanomastoid surgery, compare incidence among
      various otologic and neurotologic procedures, and discuss the possible etiology.
      STUDY DESIGN: The study design was a retrospective case review. SETTING: The
      study was conducted at a tertiary referral center. PATIENTS: The records of 486
      patients with normal facial function before tympanomastoid surgery were reviewed.
      INTERVENTION: Patients underwent tympanomastoid surgery. OUTCOME MEASURES:
      Delayed facial palsy was defined as facial palsy occurring more than 72 hours
      after surgery. RESULTS: Seven of 486 (1.4%) patients had DFP after tympanomastoid
      surgery. In two patients, the DFP was caused by a postoperative wound infection.
      Facial palsy in the other five patients likely was caused by viral reactivation.
      CONCLUSIONS: Published data for otologic surgery suggest a rising incidence of
      DFP with increased manipulation of the sensory branches of the facial nerve.
      Viral reactivation is postulated to be an important contributing mechanism in the
      development of DFP. A number of viruses could potentially cause this phenomenon,
      but observations in this study implicate the varicella zoster virus. Patients
      with a history of viral reactivation may be at greater risk for development of
      this complication.

PMID- 9918168
TI  - Soft-wall reconstruction of posterior canal wall for surgery of noninflamed ears:
      a preliminary report.
AB  - OBJECTIVE: To test whether the posterior external auditory canal (EAC) wall
      reconstructed only by soft tissues retracts after surgery in the noninflamed ear.
      STUDY DESIGN: The condition of the posterior EAC wall was observed for more than
      1 year after surgery in 20 noninflamed ears in which only the posterior EAC wall
      skin was preserved or in which the wall was reconstructed only by soft tissue
      during surgery. PATIENTS: Eighteen patients (20 ears) underwent ear surgery for
      conditions other than otitis media, including ossiculoplasty in 12 ears, cochlear
      implant in 3, resection of congenital cholesteatoma in 4, and resection of glomus
      tympanicum tumor in 1. RESULTS: Retraction of the soft posterior EAC wall was
      observed in only 1 of the 20 ears. In this ear, the posterior EAC wall showed
      only a slight retraction without any serious problems. Computed tomography
      revealed that mastoid aeration recovered in all 20 ears. CONCLUSIONS: In
      noninflamed ears, surgeons can remove the bony posterior EAC wall if necessary,
      and may not need to reinforce or reconstruct the wall with hard tissue. This
      enables surgeons to spare time and energy and obtain the same advantages as in
      the intact-canal-wall technique or canal wall reconstruction by a hard material.

PMID- 9918169
TI  - The effect of stapes surgery on high frequency hearing in patients with
      otosclerosis.
AB  - OBJECTIVE: To assess the effect of stapedectomy on high frequency hearing. STUDY
      DESIGN: A retrospective, one-group, pretest-posttest case review was performed of
      the audiometric data of patients who underwent stapedectomy at a tertiary
      referral center. PATIENTS: Thirty-eight patients (40 ears) with primary
      uncomplicated surgery were selected. Twenty-two of the patients were older than
      40 years. Preoperative and postoperative audiograms were analyzed. RESULTS:
      Preoperative and postoperative audiograms exhibited a down-sloping configuration
      toward the high frequencies. Surgery resulted in a significant improvement (p <
      0.05) from 500 to 4000 Hz in air conduction and 500 to 2000 Hz in bone
      conduction. Analysis of variance showed that age had no bearing on preoperative
      audiometric results (p < 0.05) for air conduction, bone conduction, and the air
      bone gap. Postoperatively, younger patients' 4000 to 8000 Hz (air conduction) and
      4000 Hz (bone conduction) were better than those of the older patients (p <
      0.05), but the high frequency range was still poorer than age-matched controls in
      the younger patients. CONCLUSION: Stapedectomy resulted in significant closure of
      the air bone gap between 500 to 4000 Hz, but failed to influence hearing above
      4000 Hz. Age appears to be an important variable; poorer results in the high
      frequency range were seen in the older patients who underwent stapes surgery.
      These findings, together with the residual postoperative hearing loss in the high
      frequency range in young patients, may reflect disease-specific injury resulting
      from cochlear otosclerosis.

PMID- 9918170
TI  - Differential effect of the loop diuretic furosemide on short latency auditory and
      vestibular-evoked potentials.
AB  - OBJECTIVE: This study aimed to investigate the differential effect of the loop
      diuretic furosemide on the auditory and vestibular (otolith) end organs in the
      same animals simultaneously. DESIGN AND METHODS: Auditory nerve-brain stem-evoked
      responses (ABR-generated in the cochlea) and short latency vestibular-evoked
      responses to linear acceleration impulses (L-VsEP-generated in the otolith
      organs) were recorded from albino Sabra rats both before and at minute intervals
      after intravenous injections of the loop diuretic furosemide. In some animals, an
      equal volume of saline was injected to control for the effect of the injection
      itself. In most animals, more than one injection of saline or furosemide was
      possible (furosemide, N = 17 injections in 10 rats; saline, N = 18 injections in
      9 rats). Peak-to-peak amplitude and peak latency changes in the first wave in
      each recording (representing end-organ activity) as a function of postinjection
      time were compared between the two evoked potentials using analysis of variance
      and repeated t-tests. RESULTS: Saline injections caused only minor changes in the
      amplitude of the ABR and the L-VsEP. After administration of furosemide, the
      amplitude of the L-VsEP hardly changed. However, there was a noticeable decrease
      in the amplitude of the ABR. CONCLUSIONS: Although furosemide has a major
      depressant effect on cochlear function, vestibular end-organ activity is hardly
      altered.

PMID- 9918171
TI  - Management of cochlear implant infections.
AB  - OBJECTIVE: The aim of this study was to illustrate and discuss management of
      cochlear implant infections. STUDY DESIGN: The study design was a retrospective
      case review. SETTING: This study was performed at a tertiary referral center with
      an associated Veterans Administration Hospital. PATIENTS: Postlingually deafened
      adults who had revision surgery for delayed cochlear implant infections were
      included in this study. INTERVENTION: Medical and surgical management of device
      infection without explantation. MAIN OUTCOME MEASURES: Eradication of infection
      without loss of speech reception. RESULTS: All four patients were successfully
      managed without explantation. CONCLUSIONS: Explantation of an infected but
      functioning multichannel implant is not mandatory in the absence of systemic
      sepsis.

PMID- 9918172
TI  - The influence of ionizing radiation on the CLARION 1.2 cochlear implant during
      radiation therapy.
AB  - OBJECTIVE: This study aimed to determine the maximum dose of radiation the
      CLARION 1.2 cochlear implant can withstand safely. INTRODUCTION: Cochlear
      implants restore functional hearing to patients with sensorineural deafness.
      Because some patients may need radiation therapy, it is important to investigate
      the influence of ionizing radiation on cochlear implant function. METHODS: This
      study tested the function of four CLARION 1.2 implants (Advanced Bionics, Sylmar,
      CA, U.S.A.) after varying radiation treatments with gamma rays. The first implant
      received a cumulative dosage of 69 Gy over nine treatments (single doses between
      0.1-30 Gy). The second was irradiated with a total of 90 Gy, receiving three
      treatments of 30 Gy each. The third and fourth received doses more typical of
      patient therapy (i.e., 2 Gy) approximately 30 times, for a cumulative dosage of
      approximately 60 Gy. Implant function was tested after every treatment; the
      CLARION implant incorporates a back-telemetry system, allowing impedance and
      current output testing. RESULTS: Despite the type of treatment, the results were
      quite consistent: difficulties in function occurred when the cumulative dosage
      inside the implant was approximately 60 Gy. The first implant recovered
      completely and the second recovered partially. DISCUSSION: The CLARION 1.2
      cochlear implant seems to safely withstand approximately 60 Gy of radiation
      before experiencing functional difficulties. In a clinical situation, the implant
      would not likely be in the target volume irradiated, and thus the patient's
      therapeutic cumulative dosage might be higher.

PMID- 9918173
TI  - Hearing results with deep insertion of cochlear implant electrodes.
AB  - OBJECTIVE: This study aimed to investigate the relationship of electrode
      insertion length and speech recognition in patients using Nucleus-22 cochlear
      implants. STUDY DESIGN: The study design was a retrospective review of a
      consecutive clinical series. SETTING: The study was conducted at an academic
      medical center. PATIENTS: Thirty-one postlingually deafened adults with at least
      6 months' experience with a Nucleus-22 cochlear implant using Spectra-22
      processor and SPEAK strategy participated. MAIN OUTCOME MEASURES: Open-set speech
      recognition scores for words and sentences were measured. RESULTS: Insertion
      length ranged from 22 rings (estimated 17 mm) to 32 rings (estimated 25 mm). Mean
      word recognition score was 35%. Mean sentence score was 69.6%. Statistical
      analysis showed no correlation between insertion depth and word or sentence
      scores. CONCLUSION: Insertion of the Nucleus-22 array beyond 22 rings does not
      improve performance in speech recognition. This finding cannot be generalized to
      other electrodes or processing strategies.

PMID- 9918174
TI  - Cochlear implant performance after reimplantation: a multicenter study.
AB  - OBJECTIVE: This study compares auditory performance between original and
      replacement cochlear implants. STUDY DESIGN AND SETTING: Data from 18 U.S.
      cochlear implant programs were obtained by retrospective chart review. Patients
      received and returned subjective questionnaires. PATIENTS: Twenty-eight adults
      with once-functioning Nucleus 22 cochlear implants that failed received
      replacement Nucleus 22 cochlear implants in the same ears. MAIN OUTCOME MEASURES:
      Objective measures included sentence (CID Everyday Sentences or Iowa Sentences)
      and monosyllabic word (NU-6 Words or CNC Words) speech discrimination scores.
      Patients also rated and compared performance using subjective scales. RESULTS:
      Thirty-seven percent of patients had significantly higher sentence or word scores
      with their replacement cochlear implants than with their original implants, 26%
      had no significant change, and 37% had significantly poorer scores. Subjectively,
      57% of patients reported that the performance of their replacement device was
      better or the same and 43% reported that it was poorer. There was no correlation
      between performance with the replacement cochlear implant and cause of the
      original device failure, duration of original device use before failure, surgical
      complications with either implantation, changes in electrode insertion depths, or
      preoperative variables, such as age, etiology, or duration of deafness.
      CONCLUSIONS: Speech recognition ability with a replacement cochlear implant may
      significantly increase or decrease from that with the original implant.
      Experienced cochlear implant patients facing reimplantation must be counseled
      regarding the possibility of differences in sound quality and speech recognition
      performance with their replacement device.

PMID- 9918175
TI  - Transforming growth factor-beta1 expression in human acoustic neuroma.
AB  - HYPOTHESIS: The differing clinical behavior of acoustic neuroma (AN) may be
      explained by the presence of specific biological features involved in
      tumorigenesis and growth. BACKGROUND: Transforming growth factor (TGF) beta1 is
      known to participate in the regulation of peripheral nerve tumors, modulating
      cell proliferation and differentiation with mechanisms different from those of
      glial growth factors (GGF) and fibroblastic growth factors (FGF), which are
      responsible for Schwann cells' mitogen activity. METHODS: Surgically removed
      human AN specimens were fixed in formalin and embedded in paraffin for
      immunohistochemistry studies. Expression and localization of TGF-beta1 in
      different tumor regions were assessed after incubation of paraffin sections with
      a mouse monoclonal anti-TGF beta1 antibody (DBA, Milan, Italy). Clinically, the
      time elapsed between the beginning of symptomatology and AN size as shown by
      preoperative computed tomography, magnetic resonance imaging, or both was
      calculated as rough value of growth rate, which enabled slow-growing and fast
      growing ANs to be distinguished. RESULTS: Eighty-four percent of AN specimens
      expressed TGF-beta1 positivity at the level of the cytoplasm of the Schwann
      cells. TGF-beta1 reactivity was also shown in the blood vessel walls (96.15%) and
      the tumor capsule (80.86%). TGF-beta1 reaction appeared higher in Antoni A
      regions than in Antoni B regions. No significant relationship was found between
      TGF-beta1 positivity and AN growth rate in the two groups. CONCLUSIONS: TGF-beta1
      could participate in the biological behavior of AN, particularly as an important
      factor of tumor growth prediction by allowing rapidly progressive or potentially
      recurrent tumors to be differentiated from slow-growing tumors that are unlikely
      to recur. The clinical course of patients with AN is currently still of little
      help in predicting the rate of AN growth.

PMID- 9918176
TI  - Magnetic resonance imaging of the eustachian tube in nasopharyngeal carcinoma:
      correlation of patterns of spread with middle ear effusion.
AB  - OBJECTIVE: The purpose of this study was to use multiplanar high-resolution
      magnetic resonance imaging (MRI) to detail the patterns of tumor spread in
      nasopharyngeal carcinoma (NPC) and to correlate the findings with the presence of
      an effusion in the middle ear and mastoid. MATERIALS AND METHODS: Magnetic
      resonance imaging was performed in 51 patients with newly diagnosed NPC,
      providing 102 individual sides for analysis. RESULTS: Fifty-nine lateral walls of
      the nasopharynx were involved by NPC. Tumor involved the lateral recess (55),
      eustachian tube orifice (41), levator palatini (LP) (32), torus tubarius (TT)
      (21), pharyngobasilar fascia (38), tensor palatini (TP) (17), parapharyngeal fat
      space (PFS) (19), main body of the cartilaginous eustachian tube (CET) ( 13),
      bony eustachian tube (0). middle ear (0), and inner ear (0). Effusions were
      present in 32 (54%) of the 59 involved sides. Effusions were found to be
      associated with the following patterns of spread: tumor causing major
      displacement of the CET without invasion (3 of 4), tumor invading TT or LP with
      minor displacement of the TT (4 of 7) or major displacement of the CET (7 of 7)
      and advanced invasion involving the TP, PFS, or CET with major displacement of
      CET (18 of 19). Effusions were not seen in tumors without invasion that were
      restricted to the lateral recess or eustachian tube orifice either with no
      displacement (O of I I) or with minor displacement (O of 1 1) of the TT.
      Effusions were present in 28 of 30 cases with major displacement of the main body
      of the CET, 4 of 18 with minor displacement of the TT, and 0 of 11 with no
      displacement. Displacement of the eustachian tube was a significant factor in the
      production of an effusion (p < 0.00001) and remained significant even after
      exclusion of all cases of advanced invasion (p < 0.0001). CONCLUSION: The cause
      of an effusion in NPC is multifactorial. Magnetic resonance imaging has shown
      invasion of the tensor palatini muscle in patients with an effusion, suggesting a
      functional cause. However, displacement of the eustachian tube is a significant
      factor in patients with middle ear and mastoid effusions.

PMID- 9918177
TI  - Magnetic resonance imaging and audiologic assessment of middle ear effusions in
      patients with nasopharyngeal carcinoma before radiation therapy.
AB  - OBJECTIVE: The aim of this study was to assess the performance of clinical
      methods, viz. otoscopy, pure-tone audiometry, and tympanometry in diagnosing
      middle ear effusions (MEEs) using magnetic resonance imaging as a reference
      standard. STUDY DESIGN: A retrospective study of 46 patients with newly diagnosed
      nasopharyngeal carcinoma was performed comparing clinical evaluation and
      audiometry results with magnetic resonance imaging findings obtained before
      radiation therapy. RESULTS: Twenty-two (25%) of the temporal bones imaged had
      both MEE and mastoid effusions, 24 (27%) had only middle ear fluid, and 29 (33%)
      had mastoid fluid alone. The sensitivity for tympanometry, audiometry, and
      otoscopy in detecting fluid in the middle ear was 96%, 92%, and 80%,
      respectively. Although tympanometry was most sensitive in diagnosing MEE, there
      was no statistically significant difference when comparing the overall accuracy
      of pure-tone audiometry air-bone gap and tympanometry (p = 0.7, chi-square test).
      Flat curve tympanograms (type B) only achieved a sensitivity of 45% but were of
      high specificity (92%). Forty-nine percent with negative pressure tympanograms
      (mean air pressures > -100 daPa) had no MEE. CONCLUSIONS: Using magnetic
      resonance imaging as a reference standard, tympanometry is the most sensitive
      audiologic test in detecting the presence of MEE. The overall accuracy of
      tympanometry, pure-tone audiometry air-bone gap, and otologic examination was,
      however, not significantly different.

PMID- 9918178
TI  - Topical papaverine and facial nerve dysfunction in cerebellopontine angle
      surgery.
AB  - HYPOTHESIS: Topical application of 3% papaverine hydrochloride in the
      cerebellopontine angle (CPA) produces reversible conduction block of the facial
      nerve. BACKGROUND: A case of loss of spontaneous and evoked facial muscle
      activity, and transient postoperative facial paralysis, after topical application
      of papaverine in the CPA during surgery for an acoustic neuroma using
      intraoperative cranial nerve monitoring is reported. Other cases of transient
      neurologic dysfunction after use of this drug have been reported. METHODS: A
      rabbit model of CPA surgery via suboccipital craniectomy, with intraoperative
      monitoring of the facial nerve, was used in this experiment. RESULTS: No
      significant difference in facial muscle stimulation thresholds was identified
      after application of varying concentrations of papaverine to the facial nerve in
      the CPA. CONCLUSION: Although the intraoperative event described in the report is
      suggestive of an effect of papaverine on facial nerve function, this effect could
      not be reproduced in an established animal model of CPA surgery.

PMID- 9918179
TI  - A human temporal bone study of stapes footplate movement.
AB  - OBJECTIVE: This study was designed to determine whether stapes movement is
      pistonlike or complex. BACKGROUND: The literature provides conflicting
      information on whether stapes footplate motion is only pistonlike or has other
      types of movement, such as hingelike or rocking. METHODS: Using 10 freshly
      harvested human cadaver temporal bones, 3 targets were placed on the stapes
      footplate through an extended facial recess approach. The targets were 0.5-mm
      pieces of reflective adhesive material positioned on the long axis of the
      footplate at the anterior crus, central footplate, and posterior crus.
      Displacement and phase of the three targets were measured from 0.2 to 10 kHz at a
      90dB sound pressure level input at the tympanic membrane. The measuring system
      was a sophisticated laser Doppler vibrometer (LDV). A computer program (Tymptest)
      calculated footplate displacement and relative phase at the three sites and the
      ratio of anterior-posterior rocking movement of the footplate long axis to
      displacement at the center. RESULTS: Below 2.0 kHz, stapes vibration is
      predominately pistonlike. Above 2.0 kHz, anterior-posterior rocking motion
      increases logarithmically with frequency, and, near 4.0 kHz, rocking and
      pistonlike motion are approximately equal. CONCLUSIONS: Stapes footplate
      vibration is primarily pistonlike up to 2.0 kHz but becomes more complex at
      higher frequencies because of an increase in anterior-posterior rocking motion.
      Hingelike movements were not observed. This information may be helpful in the
      design of ossicular replacement prostheses that mimic or improve upon normal
      stapes vibration.

PMID- 9918180
TI  - The effect of cochleostomy and intracochlear infusion on auditory brain stem
      response threshold in the guinea pig.
AB  - HYPOTHESIS: Cochleostomy followed by intracochlear infusion, as a model system
      for continuous drug delivery, may be well tolerated by the auditory system with
      preservation of hearing. BACKGROUND: The infusion of therapeutic agents, such as
      neurotrophins, growth factors, anti-inflammatory drugs, and viral gene therapy
      vectors, into the cochlea over a prolonged period of time may be desirable to
      reduce cochlear damage after auditory insult. However, the effects of continuous
      cochlear infusion have not been studied adequately. METHODS: Eight Hartley guinea
      pigs underwent left cochleostomy with infusion of artificial perilymph (n = 7) or
      0.85% saline (n = 1). The artificial perilymph or 0.85% saline was administered
      by an osmotic minipump (Alza, Palo Alto, CA, U.S.A., model 2002; infusion rate
      0.5 microL/hr, mean pumping duration of 2.5 weeks) connected to the cochlea by a
      fine plastic cannula (Inner Diameter = 0.28 mm, Outer Diameter = 0.61 mm) that
      enters the scala tympani via a cochleostomy. Hearing was assessed by determining
      auditory brain stem response (ABR) thresholds before surgery and on postoperative
      days 3 and 7 for artificial perilymph infused animals and before surgery and on
      postoperative days 3, 7, 14, 21, and 28 for the single saline-infused animal. The
      ABR thresholds were determined with a click and at the following frequencies: 1
      kHz, 2 kHz, 4 kHz, 8 kHz, 16 kHz, 20 kHz, and 30 kHz. RESULTS: There was a
      preservation of preoperative ABR thresholds in the lower frequencies (1, 2 kHz),
      mild elevation (< or =10 dB) in the midfrequencies (4, 8 kHz), and marked rise >
      or =>30 dB) in the ABR thresholds at higher frequencies (>16 kHz). Surprisingly,
      the single long-term animal showed recovery of hearing in midfrequencies and high
      frequencies with the passage of time. CONCLUSIONS: Cochleostomy and intracochlear
      infusion result in auditory insult limited largely to the region of surgical
      trauma. Demonstration of hearing preservation after surgical breach of the
      cochlea should encourage further development of potential diagnostic and
      therapeutic intervention into the inner ear.

PMID- 9918181
TI  - Imaging case of the month: bilateral empty internal auditory canal.

PMID- 9918182
TI  - Pathology case of the month: otosclerosis of the cochlear capsule: correlation of
      computerized tomography and histopathology.

PMID- 9918183
TI  - Management of facial nerve injury due to temporal bone trauma.
AB  - OBJECTIVE: This article provides an overview of relevant data regarding the
      management of facial nerve injury due to temporal bone trauma. DATA SOURCES:
      Sources used were relevant English language clinical and basic science
      publications. STUDY SELECTION: A Medline search dating back to 1966 for articles
      concerning temporal bone trauma and facial nerve injury including both human and
      animal data was performed. Articles were included if they contained relevant data
      or were significant reviews on the subject. A retrograde bibliography search was
      then conducted to acquire any articles that may have been missed by the
      computerized search, including those papers published prior to 1966. DATA
      EXTRACTION: The data from each paper were reviewed individually. DATA SYNTHESIS:
      The data were not amenable to formal meta-analysis or valid data summarization.
      CONCLUSIONS: Patients who should not require surgical intervention include those
      who have: documented normal facial nerve function after injury regardless of
      progression, presentation with incomplete facial nerve paralysis with no
      progression to complete paralysis, and degeneration <95% on ENoG. The remaining
      patients presumably have a poorer prognosis for return of facial nerve function
      although it remains unclear exactly how poor the return of function will be.
      Decompression surgery likely has a beneficial effect if performed within 14 days
      of injury, so those patients with expected poor natural outcomes may be offered
      this intervention. Late decompression surgery is not recommended. Late
      exploratory surgery is recommended only in those patients who do not experience
      adequate recovery of facial nerve function and likely require nerve repair.
      Despite the availability of a relatively large volume of published data, there
      remain many unanswered questions.

PMID- 9918184
TI  - Cracking the auditory genetic code: nonsyndromic hereditary hearing impairment.
AB  - OBJECTIVE: The application of molecular genetic techniques to the study of
      hereditary hearing impairment has contributed significantly to our understanding
      of the genetics of deafness. This article reviews the current state of our
      knowledge regarding the mapping and identification of genes associated with
      nonsyndromic hereditary hearing impairment. DATA SOURCES: Data were obtained from
      the medline database, the Molecular Biology of Deafness Meeting, and the
      Internet. STUDY SELECTION: Articles reporting information about the genetics of
      deafness were selected. DATA EXTRACTION: Data pertaining to auditory phenotype,
      location of genes, identification of genes, and implication for hearing were
      extracted. CONCLUSIONS: Significant progress has been made in understanding the
      molecular pathogenesis of deafness.

PMID- 9918185
TI  - Clarifications requested re: cochlear modiolar defects.

PMID- 9918186
TI  - Hereditary recessive progressive SNHL--what is the incidence?

PMID- 9918187
TI  - Avicenna of Persia.

PMID- 9918188
TI  - "Ethics" of stapedectomy.

PMID- 9918189
TI  - Is stapedectomy ever ethical? Never say "ever".

PMID- 9918190
TI  - Is stapedectomy ever ethical?--Faulty premise, faulty conclusion.

PMID- 9918191
TI  - Is stapedectomy ever ethical? An audiologist replies.

PMID- 9918192
TI  - Diabetes complications and their potential prevention: aldose reductase
      inhibition and other approaches.
AB  - Despite recent advances both in the chemistry and molecular pharmacology of
      antidiabetic drugs, diabetes still remains a life-threatening disease, which
      tends to spread all over the world. The clinical profile of diabetic subjects is
      often worsened by the presence of several long-term complications, namely
      neuropathy, nephropathy, retinopathy, and cataract. Several attempts have been
      made to prevent or at least to delay them. The most relevant are reported in this
      review, including the development of compounds acting as aldose reductase
      inhibitors, anti-advanced glycation end-product drugs, free radical scavengers,
      vasoactive agents, essential fatty acid supplementation, and neurotropic growth
      factors.

PMID- 9918193
TI  - Nitrogen-containing heteroalicycles with serotonin receptor binding affinity:
      development of gastroprokinetic and antiemetic agents.
AB  - To obtain gastroprokinetic agents with more potent and selective activity than
      metoclopramide and cisapride, a series of N-(4-benzyl-2
      morpholinylmethyl)benzamides were designed and prepared. Their synthesis and
      structure-activity relationships were described. As a result, mosapride was
      selected as a promising candidate for potent gastroprokinetic activity with
      selective 5-HT4 receptor agonistic activity. As an extension to this project, the
      novel benzamide and the carboxamide derivatives having 1-benzyl-4-methylhexahydro
      1,4-diazepine ring in the amine moiety were prepared and evaluated for 5-HT3
      receptor antagonistic activity. DAT-582 was identified as an antiemetic agent in
      cancer chemotherapy. The asymmetric synthesis of DAT-582 and the SAR studies were
      briefly reviewed. In further modifications of the N-(1-benzyl-4-methylhexahydro
      1,4-diazepin-6-yl)benzamides, the novel nicotinamides with 1-ethyl-4
      methylhexahydro-1,4-diazepin ring were found to have potent 5-HT3 and dopamine D2
      and D3 receptor antagonistic activities and to show weak central nervous system
      depression and extrapyramidal syndrome. After extensive SARs, AS-8112 was
      selected as a broad antiemetic agent.

PMID- 9918194
TI  - Role of natriuretic peptides in ion transport mechanisms.
AB  - Natriuretic peptides (NP) act as ligands on the guanylyl cyclase family of
      receptors. The NP binding site on these receptors is extracellular and the
      guanylyl cyclase and protein kinase domains are intracellular. The guanylyl
      cyclase receptor catalyzes the synthesis of the second messenger molecule, cGMP,
      which activates protein kinase. This in turn is involved in the phosphorylation
      of various ion transport proteins. Ion transport proteins, which are modulated by
      NP and are thought to underlie the natriuretic and diuretic actions of NP,
      include: (a) calcium-activated K+ channels; (b) ATP-sensitive K+ channels; (c)
      inwardly-rectifying K+ channels; (d) outwardly-rectifying K+ channels; (e) L-type
      Ca2+ channels; (f) Cl- channels including cystic fibrosis transmembrane
      conductance regulator Cl- channels; (g) Na+- K+ 2Cl- co-transporter; (h) Na+- K+
      ATPase; (i) Na+ channels; (j) stretch-activated channels; and (k) water channels.
      It appears that NP modulate the kinetics, rather than the conductance, of ion
      channels. Some of these channels, like the Ca2+, ATP-sensitive K+ and stretch
      activated channels, are also involved in NP secretion. In addition, the
      structural properties of the NP, e.g., ovCNP-22 and ovCNP-39, appear to confer on
      them the ability to form ion channels. These CNP-formed ion channels can modify
      the trans-membrane signal transduction and second messenger systems underlying NP
      induced pathological effects.

PMID- 9918195
TI  - Topotecan: what dose, what schedule, what route?

PMID- 9918196
TI  - Doxorubicin-polymer conjugates: further demonstration of the concept of enhanced
      permeability and retention.

PMID- 9918197
TI  - Immunological effects of interleukin 12 administered by bolus intravenous
      injection to patients with cancer.
AB  - The immunological effects of recombinant human interleukin 12 (rhIL-12)
      administration were examined during the conduct of a Phase I clinical trial.
      Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in
      doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN
      gamma levels were seen during rhIL-12 therapy. Significant lymphopenia was
      observed 24 h after single i.v. injections of rhIL-12 at each dose level. The
      degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL
      12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at
      approximately 10 h after rhIL-12 injection and returned to baseline within 14
      days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy,
      was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced
      lymphopenia involved all major lymphocyte subsets, although natural killer (NK)
      cell numbers were the most profoundly affected, and CD4 T-cell numbers were the
      least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface
      of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells
      obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell
      cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear
      cells obtained after lymphocyte recovery following the administration of a single
      500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four
      of four patients tested and enhanced T-cell proliferation in three of four
      patients tested. These studies confirm that doses of rhIL-12 resulting in
      significant immunological activity can be administered with acceptable toxicity
      to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell
      and T-cell function that are associated with advanced cancer in humans.

PMID- 9918198
TI  - Deletions of chromosome 4 at multiple sites are frequent in malignant
      mesothelioma and small cell lung carcinoma.
AB  - Recent allelotyping studies suggest that allelic losses at one or both arms of
      chromosome 4 are frequent in several tumor types. Cytogenetic studies of
      malignant mesothelioma (MM) and comparative genomic hybridization analyses of
      small cell lung carcinoma (SCLC) suggest that chromosome 4 deletions may also
      play a role in these tumor types, although these results have not been confirmed
      by allelotyping. In an effort to more precisely identify and map the locations of
      putative tumor suppressor gene(s) on chromosome 4 involved in the pathogenesis of
      these tumors, we performed loss of heterozygosity studies using 16 polymorphic
      microsatellite markers. After precise microdissection of archival surgical cases,
      we studied DNA obtained from 20 MMs, 21 SCLCs, and 20 non-SCLCs (NSCLCs). In
      addition, DNA from 14 SCLC and 17 NSCLC cell lines and corresponding B
      lymphoblastoid lines were studied. In MM and SCLC, we observed frequent losses at
      three nonoverlapping regions: (a) 4q33-34 (region R1; >80%); (b) 4q25-26 (region
      R2; >60%); and (c) 4p15.1-15.3 (region R3; >50%). Losses at these sites occurred
      at lower frequencies in NSCLC (>20-30%). Data from tumors and cell lines were
      similar. In MM and SCLC, the most frequently observed pattern was loss at all
      three regions. However, in NSCLC, the most frequent pattern was loss at R3 alone.
      Our study has delineated three nonoverlapping regions of frequent deletions on
      chromosome 4 in MM and SCLC, suggesting that there may be three putative
      suppressor genes on chromosome 4, the inactivation of which may be important in
      the pathogenesis of these tumor types.

PMID- 9918199
TI  - Relative expression of E-cadherin and type IV collagenase genes predicts disease
      outcome in patients with resectable pancreatic carcinoma.
AB  - We examined the expression level of several genes that regulate distinct steps of
      metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary
      human pancreatic carcinomas from patients undergoing curative surgery. The
      expression of epidermal growth factor receptor, E-cadherin, type IV collagenase
      [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor,
      vascular endothelial growth factor/vascular permeability factor, and interleukin
      8 was examined by a colorimetric in situ mRNA hybridization technique. Down
      regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP
      2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349,
      respectively) had significant prognostic value. The ratio of type IV collagenase
      expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression
      (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in
      patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease
      free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly
      associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis
      (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of
      eight patients alive 28-64 months after surgery. Multivariate analysis of overall
      survival showed that the MMP:E-cadherin ratio was a significant independent
      prognostic factor, whereas stage, nodal metastasis, and histological type were
      not. These data show that multiparametric analysis for several metastasis-related
      genes may allow physicians to assess the metastatic potential and hence predict
      the clinical outcome of individual patients with resectable pancreatic carcinoma.

PMID- 9918200
TI  - Treatment with farnesyl-protein transferase inhibitor induces regression of
      mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu
      transgenic mice by inhibition of mitogenic activity and induction of apoptosis.
AB  - Mouse mammary tumor virus-transforming growth factor alpha (MMTV-TGF alpha) and
      MMTV-TGF alpha/neu transgenic mice develop mammary tumors after a long latency
      and therefore provide useful model systems for breast cancer with its recognized
      activation of receptor tyrosine kinase signaling. We used these mice to study the
      antitumor effect of L-744,832 (FTI), a potent and selective inhibitor of farnesyl
      protein transferase, and hence of Ras function. A total of 55 mice were assigned
      randomly to treatment with FTI or vehicle, and one-half of the mice were crossed
      over after initial treatment to the opposite group. L-744,832 induced reversible
      regression of mammary tumors that was paralleled by a decrease in serum levels of
      TGF alpha secreted by the tumor cells. There was no difference in response to
      treatment with FTI between MMTV-TGF alpha mice, in which tumorigenesis was
      accelerated by multiparity or the chemical carcinogen 7,12
      dimethylbenzanthracene, and MMTV-TGF alpha/neu mice. The tumor histological type
      had no impact on FTI sensitivity. For mechanistic analyses, tumor excision
      biopsies were obtained from 12 mice before and after treatment with L-744,832. In
      these samples, tumor regression was paralleled biochemically by inhibition of
      mitogen-activated protein kinase activity and biologically by an increase in G1
      phase and decrease in S-phase fractions, as well as induction of apoptosis. These
      results suggest that the potential clinical use of FTI could be expanded to
      include cancers harboring activated receptor tyrosine kinases as well as those
      containing activated Ras.

PMID- 9918202
TI  - Pretreatment with a monoclonal antibody/interleukin-2 fusion protein directed
      against DNA enhances the delivery of therapeutic molecules to solid tumors.
AB  - The efficacy of molecular therapies for human malignancies is limited by
      inadequate accumulation within solid tumors. Our laboratory has developed a novel
      approach that uses monoclonal antibodies (MAbs) to direct vasoactive proteins to
      tumor sites to increase local vascular permeability and, in turn, improve the
      delivery of therapeutic reagents. Previously, we demonstrated that pretreatment
      with immunoconjugates containing interleukin-2 (IL-2) enhances specific tumor
      uptake of radiolabeled MAbs without affecting normal tissues. In the present
      study, we describe a fusion protein consisting of a chimeric antinuclear antibody
      and IL-2 (chTNT-3/IL-2) and illustrate its potential for improving the delivery
      of both MAbs and drugs. The ability of pretreatment with chTNT-3/IL-2 to increase
      specific tumor uptake of the MAb B72.3 was demonstrated in LS174T colon tumor
      bearing mice. Tumor accretion of B72.3 increased nearly 3-fold, with no changes
      in normal tissues. Abrogation of this effect with N(G)-methyl-1-arginine, a
      chemical inhibitor of nitric oxide synthase, suggests that rapid generation of
      nitric oxide in the tumor is responsible for the enhanced uptake. To demonstrate
      that pretreatment with chTNT-3/IL-2 can improve the uptake of other clinically
      relevant MAbs in different tumor models, additional studies were performed in
      both lung and prostate xenograft models. Pretreatment with the fusion protein
      increased specific tumor uptake of the MAb NR-LU-10 in A427 lung tumor-bearing
      mice and enhanced tumor uptake of the MAb CYT-351 in LNCaP prostate tumor-bearing
      mice, 2.1-fold and 1.7-fold, respectively. Finally, tumor uptake of the
      radiolabeled thymidine analogue 125IUdR also increased approximately 3-fold after
      pretreatment, indicating that this approach can be extended to small molecules
      such as chemotherapeutic drugs. Because TNT-3 recognizes a universal nuclear
      antigen accessible in degenerating and necrotic cells within all solid tumors,
      this strategy may be applicable to the majority of human cancers.

PMID- 9918201
TI  - Interleukin-6 modulated conditionally replicative adenovirus as an
      antitumor/cytotoxic agent for cancer therapy.
AB  - In this study, we report that an interleukin-6 (IL-6)-inducible E1A-substituting
      activity can be exploited for the production of infectious adenoviral particles
      during infection with the E1A-deleted adenovirus (Ad) Ad5dl312. The basal level
      of complementation can be increased by 1.5 log by induction of the HepG2 cells
      with recombinant human IL-6. Additionally, the IL-6-inducible E1A-substituting
      activity can complement E1A deletion in other cancer cell lines to render them Ad
      producer cells on induction with recombinant human IL-6, although the efficiency
      of complementation varies between cell lines. Ad5dl312 can replicate in, produce
      cytotoxic effect, and kill human tumor cells without addition of exogenous IL-6
      in the context of tumor cells possessing an IL-6 autocrine arc, such as ovarian
      tumor cells. In contrast, normal human mesothelial cells isolated from normal
      human peritoneum lining do not support replication of Ad5dl312, even in the
      presence of exogenous IL-6. These results suggest that Ad5dl312 could be used as
      a cytotoxic agent to selectively kill tumor cells responsive to or possessing an
      IL-6 autocrine arc.

PMID- 9918203
TI  - Cyclic-AMP induction of gap junctional intercellular communication increases
      bystander effect in suicide gene therapy.
AB  - The phenomenon of the "bystander effect" (BE) observed in suicide gene therapy
      studies leads to the intriguing possibility that cytotoxicity can be achieved
      even in tumor cells that have not themselves been targeted with novel genetic
      material. There is considerable data suggesting the role of gap junction-mediated
      intercellular communication (GJIC) in the BE. Transfer of connexin (Cx)-encoding
      genes, the building blocks of GJIC, has been shown both in vitro and in vivo to
      increase the BE. Since the loss of GJIC is a common feature of cancer cells, we
      examined the consequence of GJIC up-regulation on the BE in suicide gene therapy.
      We used 8-bromo-cyclic-AMP to induce Cx43 and GJIC. In mixing assays, using
      various proportions of cells containing viral thymidine kinase delivered by an
      adenoviral delivery system or stably transduced by a retrovirus vector, 8-bromo
      cyclic-AMP enhanced the BE of cell killing using ganciclovir. The induction in
      cell killing was more significant when a low percentage of the cell population
      was infected, which is the relevant clinical situation. We have demonstrated that
      this is not due to an effect on infectivity or suicide gene expression. Since
      decreased GJIC is part of the transformed phenotype, induction of Cxs provides an
      element of selectivity to suicide gene therapy. Our study adds strength to the
      rationale to develop clinically tolerable GJ inducers to potentiate the effect of
      suicide gene therapy via the BE.

PMID- 9918204
TI  - A comparison of clinical pharmacodynamics of different administration schedules
      of oral topotecan (Hycamtin)
AB  - Prolonged exposure to topotecan in in vitro and in vivo experiments has yielded
      the highest antitumor efficacy. An oral formulation of topotecan with a
      bioavailability of 32-44% in humans enables convenient prolonged administration.
      Pharmacokinetic/pharmacodynamic relationships from four Phase I studies with
      different schedules of administration of oral topotecan in 99 adult patients with
      malignant solid tumors refractory to standard forms of chemotherapy were
      compared. Topotecan was administered as follows: (a) once daily (o.d.) for 5 days
      every 21 days (29 patients); (b) o.d. for 10 days every 21 days (19 patients);
      (c) twice daily (b.i.d.) for 10 days every 21 days (20 patients); and (d) b.i.d.
      for 21 days every 28 days (31 patients). Pharmacokinetic analysis was performed
      in 55 patients using a validated high-performance liquid chromatographic assay
      and noncompartmental pharmacokinetic methods. Totals of 109, 48, 64, and 59
      courses were given, respectively. Dose-limiting toxicity consisted of
      granulocytopenia for the o.d. x 5-day dosage, a combination of myelosuppression
      and diarrhea in both of the 10-day schedules, and only diarrhea in the 21-day
      schedule. Pharmacokinetics revealed a substantial variation of the area under
      curve (AUC) of topotecan lactone in all of the dose schedules with a mean
      intrapatient variation of 25.4 +/- 31.0% (o.d. x 5), 34.5 +/- 25.0% (o.d. x 10),
      96.5 +/- 70.1% (b.i.d. x 10), and 59.5 +/- 51.0% (b.i.d. x 21). Significant
      correlations were observed between myelotoxicity parameters and AUC(t) day 1 and
      AUC(t) per course of topotecan lactone. In all of the studies, similar sigmoidal
      relationships could be established between AUC(t) per course and the percentage
      decrease of WBCs. At maximum-tolerated dose level, no significant difference in
      AUC(t) per course was found [AUC(t) per course was 107.4 +/- 33.7 ng x h/ml (o.d.
      x 5), 145.3 +/- 23.8 ng x h/ml (o.d. x 10), 100.0 +/- 41.5 ng x h/ml (b.i.d. x
      10), and 164.9 +/- 92.2 ng x h/ml (b.i.d. x 21), respectively.] For oral
      topotecan, the schedule rather than the AUC(t)-per-course seemed to be related to
      the type of toxicity. Prolonged oral administration resulted in intestinal side
      effects as a dose-limiting toxicity, and short-term administration resulted in
      granulocytopenia. On the basis of this pharmacokinetic study, no schedule
      preference could be expressed, but based on patient convenience, administration
      once daily for 5 days could be favored.

PMID- 9918205
TI  - Immunization of melanoma patients with BEC2-keyhole limpet hemocyanin plus BCG
      intradermally followed by intravenous booster immunizations with BEC2 to induce
      anti-GD3 ganglioside antibodies.
AB  - BEC2 is an anti-idiotypic mouse monoclonal antibody that mimics GD3 ganglioside.
      Previous clinical trials demonstrated that intradermal immunization using 2.5 mg
      of BEC2 with BCG or i.v. immunization with 10 mg of BEC2 can induce anti-GD3
      antibodies in a subset of patients. We hypothesized that combining these two
      immunization strategies might be more effective in inducing anti-GD3 antibodies
      and that conjugation of BEC2 to keyhole limpet hemocyanin (KLH) would further
      enhance the immunogenicity of BEC2. In this clinical trial, 18 melanoma patients
      who were free of disease after complete surgical resection within 1-6 months
      received intradermal immunizations on weeks 0, 2, 4, 6, and 10 with 2.5 mg of
      BEC2 conjugated to KLH and mixed with BCG (BEC2-KLH/BCG). Booster immunizations
      of 10 mg of unconjugated BEC2 were administered i.v. on weeks 24, 37, and 50.
      Four of 18 patients (22%) developed IgM anti-GD3 antibodies. No IgG anti-GD3
      antibodies were detected. All four responding patients developed anti-GD3 IgM
      during immunization with BEC2-KLH/BCG; only one patient demonstrated a reboost of
      the IgM anti-GD3 titer during the i.v. immunizations. Thirteen of the patients
      are free of melanoma (3 after undergoing re-resection for local relapse); 14
      patients (78%) remain alive with a median follow-up of 28 months. These results
      confirm our previous trial, showing that BEC2 with BCG can induce anti-GD3
      antibodies in patients. The data do not provide evidence that conjugation to KLH
      increases the immunogenicity of BEC2 when it is administered with BCG.

PMID- 9918206
TI  - Phase I clinical and pharmacokinetic study of PK1 [N-(2
      hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class
      of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign
      Phase I/II Committee.
AB  - PK1 comprises doxorubicin covalently bound to N-(2-hydroxypropyl)methacrylamide
      copolymer by a peptidyl linker. Following cellular uptake via pinocytosis, the
      linker is cleaved by lysosomal enzymes, allowing intratumoral drug release.
      Radically altered plasma and tumor pharmacokinetics, compared to free
      doxorubicin, and significant activity in animal tumors have been demonstrated
      preclinically. We aimed to determine the maximum tolerated dose, toxicity
      profile, and pharmacokinetics of PK1 as an i.v. infusion every 3 weeks to
      patients with refractory or resistant cancers. Altogether, 100 cycles were
      administered (range, 20-320 mg/m2 doxorubicin-equivalent) to 36 patients (20
      males and 16 females) with a mean age of 58.3 years (age range, 34-72 years). The
      maximum tolerated dose was 320 mg/m2, and the dose-limiting toxicities were
      febrile neutropenia and mucositis. No congestive cardiac failure was seen despite
      individual cumulative doses up to 1680 mg/m2. Other anthracycline-like toxicities
      were attenuated. Pharmacokinetically, PK1 has a distribution t(1/2) of 1.8 h and
      an elimination t(1/2) averaging 93 h. 131I-labeled PK1 imaging suggests PK1 is
      taken up by some tumors. Responses (two partial and two minor responses) were
      seen in four patients with NSCLC, colorectal cancer, and anthracycline-resistant
      breast cancer. PK1 demonstrated antitumor activity in refractory cancers, no
      polymer-related toxicity, and proof of principle that polymer-drug conjugation
      decreases doxorubicin dose-limiting toxicities. The recommended Phase II dose is
      280 mg/m2 every 3 weeks. Studies are planned in colorectal, NSCLC, and breast
      cancer patients.

PMID- 9918207
TI  - Hepatic transcatheter arterial chemoembolization alternating with systemic
      protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies
      metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium
      (PSOC 1104).
AB  - We assessed a regimen of alternating regional and systemic therapy in patients
      with gastrointestinal malignancies with liver-dominant metastases for
      feasibility, toxicity, response rate, response duration, patterns of progression,
      and progression-free and overall survival. Regional therapy comprised selective
      hepatic transcatheter arterial chemoembolization (TACE) using a suspension of
      cisplatin and particulate polyvinyl alcohol. This procedure was delivered between
      cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic
      chemotherapy. Patient eligibility criteria included: (a) having histologically
      documented adenocarcinoma arising from a gastrointestinal primary site with
      unresectable liver metastases bidimensionally measurable on computerized
      tomography scan; (b) age greater than 18 years; and (c) performance status 0-2
      (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by
      the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with
      the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3,
      which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between
      each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given
      for 28 days of each 35-day cycle until toxicity or progression. Between December
      23, 1991, and January 19, 1995, 32 patients were registered in this trial, of
      whom 27 were eligible; 20 completed one or more treatment cycles and were
      evaluable for radiographic response. Patients with colorectal liver metastases
      predominated (74%). Twelve (44%) of 27 patients had failed one or more prior
      treatment regimens. There were no treatment-related deaths, and hematological and
      hepatic toxicities were generally manageable and reversible. Two patients,
      however, developed hepatic abscesses requiring drainage, and one patient
      developed an infarcted gallbladder, which necessitated cholecystectomy. There
      were no patients with complete responses; there were 8 (40%) with partial
      responses, 4 (20%) with minor responses, 2 (10%) with stable disease, and 6 (30%)
      who progressed on the treatment. The median duration of response for partial
      responders was 4.2 months (127 days; range, 56-245 days). The median reduction in
      carcinoembryonic antigen for responders was 87.5%. Two patients underwent
      subsequent resection of residual metastases; one of them is still alive at 58.4
      months follow-up. The predominant site of disease progression was the liver; 25%
      of the patients progressed in extrahepatic sites. The median overall survival for
      the whole group is 14.3 months (95% confidence interval, 7.2-16.2). Actuarial
      overall survival for the whole group at 1 year and 2 years is 57 and 19%,
      respectively. Alternating systemic PCI-5FU and regional TACE (cisplatin/polyvinyl
      alcohol) is an active and feasible regimen with manageable toxicities in patients
      with metastatic gastrointestinal malignancies with liver-dominant disease and
      merits further investigation. The complications seen were in line with those
      reported at other specialized centers.

PMID- 9918208
TI  - Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride
      (AG337, THYMITAQ) administered orally for 5 days.
AB  - Phase I studies of p.o. administered nolatrexed dihydrochloride (AG337,
      THYMITAQ), a nonclassical thymidylate synthase inhibitor, were performed to
      establish the maximum tolerated dose and a recommended dose for Phase II studies.
      The bioavailability and pharmacokinetic and pharmacodynamic properties of oral
      nolatrexed were also studied. Forty-five patients were treated with oral
      nolatrexed every 6 h for 5 days at doses of 288-1000 mg/m2/day. The
      bioavailability of the oral preparation was determined, and the effect of a
      standard meal on nolatrexed absorption was investigated at a dose of 800
      mg/m2/day. Nolatrexed plasma concentrations were analyzed by high-performance
      liquid chromatography. Nolatrexed was rapidly absorbed with a median
      bioavailability of 89% (range 33-116%), with 88% of patients above 70%. The dose
      limiting toxicities were gastrointestinal, and the recommended Phase II oral dose
      was 800 mg/m2/day. After a standard meal, the peak plasma nolatrexed
      concentration achieved was lower (median, 8.3 microg/ml versus 15.0 microg/ml; P
      = 0.001), and the time taken to reach the peak was longer (median, 180 min versus
      45 min; P = 0.00003), but the trough concentration was higher (median, 3.6
      microg/ml versus 2.1 microg/ml; P = 0.004) when compared with the fasted state.
      The area under the nolatrexed plasma concentration versus time curve was not
      affected by food. Average trough nolatrexed concentration, but not dose, was
      significantly related to the % decrease in both thrombocytes (r2 = 0.58; C50 =
      6.0 microg/ml, where C50 is the plasma concentration associated with a 50%
      decrease in thrombocytes) and neutrophils (r2 = 0.63; C50 = 0.6 microg/ml).
      Nolatrexed can be safely administered as an oral preparation at a dose of 800
      mg/m2/day for 5 days. Bioavailability was close to 100% and, because inhibition
      of thymidylate synthase by nolatrexed is rapidly reversible, the slower
      absorption after a standard meal may result in a shorter duration of
      noninhibitory concentrations between doses.

PMID- 9918209
TI  - The nuclear factor-kappa B RelA transcription factor is constitutively activated
      in human pancreatic adenocarcinoma cells.
AB  - Pancreatic adenocarcinoma is a leading cause of adult cancer mortality in the
      United States. Recent studies have revealed that point mutation of the K-ras
      oncogene is a common event in pancreatic cancer, and oncogenesis mediated by Ras
      may also involve activation of Rel/nuclear factor (NF)-kappa B transcription
      factors. Furthermore, the c-rel member of Rel/NF-kappa B transcription factor
      family was first identified as a cellular homologue of the v-rel oncogene,
      suggesting that other members of the Rel/NF-kappa B family are potentially
      oncogenes. We therefore investigated the possibility that Rel/NF-kappa B
      transcription factors are activated in pancreatic cancer. Immunohistochemical
      analysis, Western blot and Northern blot analysis, electrophoretic mobility shift
      assays, and chloramphenicol acetyltransferase assays were performed to determine
      RelA activity in human pancreatic adenocarcinomas and normal tissues and
      nontumorigenic or tumorigenic cell lines. RelA, the p65 subunit of NF-kappa B,
      was constitutively activated in approximately 67% (16 of 24) of pancreatic
      adenocarcinomas but not in normal pancreatic tissues. Constitutive RelA activity
      was also detected in 9 of 11 human pancreatic tumor cell lines but not in
      nontumorigenic Syrian golden hamster cell lines. I kappa B alpha, a previously
      identified NF-kappa B-inducible gene, was overexpressed in human pancreatic tumor
      tissues and cell lines, and RelA activation could be inhibited by curcumin and
      dominant-negative mutants of I kappa B alpha, raf, and MEKK1. This is the first
      report demonstrating constitutive activation of RelA in nonlymphoid human cancer.
      These data are consistent with the possibility that RelA is constitutively
      activated by the upstream signaling pathway involving Ras and mitogen-activated
      protein kinases in pancreatic tumor cells. Constitutive RelA activity may play a
      key role in pancreatic tumorigenesis through activation of its downstream target
      genes.

PMID- 9918210
TI  - p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with
      lung cancer susceptibility and prognosis.
AB  - An association between the BstUI (Pro/Pro) genotype of the p53 codon 72
      polymorphism and lung cancer has been reported previously (X. Jin et al.,
      Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution
      of p53 codon 72 polymorphism as well as the association of this polymorphism with
      lung cancer risk and prognosis remain undefined in the Taiwanese population.
      Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism
      in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies
      in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis
      indicated significant differences in genotype distribution of p53 from other
      reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United
      States (P = 0.002), and African-Americans (P = 0.027). In addition, our data
      suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk
      of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro
      showed a significantly increased odds ratio (3.14; confidence interval, 1.48
      6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls
      with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of
      2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other
      genotypes to be diagnosed with lung cancer at the early ages. We further
      investigated the association of p53 codon 72 polymorphism with prognosis in 133
      lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer
      prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test).
      Our data suggested that p53 codon 72 polymorphism may play a role in cancer
      susceptibility and prognosis in specific classes of lung cancer patients in
      Taiwan.

PMID- 9918211
TI  - Changes of angiogenesis and tumor cell apoptosis during colorectal
      carcinogenesis.
AB  - Activation of the angiogenic process occurs during tumorigenesis, as does
      disturbance of cell proliferation and apoptosis. Seeking a potential correlation,
      we investigated tumor cell apoptosis, proliferation, and angiogenesis in the
      adenoma-carcinoma sequence of colorectal carcinogenesis using an in situ
      apoptosis detection kit and MIB-1 and anti-CD34 antibodies in 27 adenomas with
      low dysplasia, 17 adenomas with high dysplasia, and 26 carcinomas in adenoma, as
      well as assessed p53 and bcl-2 expressions. The results showed that the potential
      for apoptosis was augmented, paralleling the increment of proliferation, in
      adenomas with low dysplasia but diminished when adenomas progressed from low
      dysplasia to high dysplasia and cancer. A gradual increment of microvessel
      density was observed during the progression with an increase during transition
      from low dysplasia to high dysplasia and cancer. Correlation coefficient test
      showed an inverse correlation between apoptotic index and microvessel density
      when all of the lesions were taken into account. No apparent impact of aberrant
      p53 on angiogenesis or bcl-2 on apoptosis was observed in this study. These
      results suggest that the angiogenesis initiates during transition from low
      dysplasia to high dysplasia and cancer, which may, in turn, contribute to the
      reduction of tumor cell apoptosis during colorectal carcinogenesis.

PMID- 9918212
TI  - Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid
      in humans.
AB  - Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United
      States, is the second leading cause of cancer-related deaths of males in this
      country. Because of the poor success rate in the treatment of PCA, an
      intervention at an early stage may reduce the progression of small carcinoma to
      large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts
      are needed to establish mechanism-based approaches to develop: (a) the markers
      for early detection of the disease as well as toward monitoring the efficacy of
      treatment(s); and (b) novel chemopreventive strategies against PCA. Using unique
      samples of pair-matched benign and cancer tissue obtained from the same PCA
      patient, we showed that ornithine decarboxylase (ODC) activity is significantly
      (P < 0.001) elevated in PCA (1142 +/- 100; mean +/- SE) than in paired benign
      tissue (427 +/- 51; mean +/- SE). The immunoblot analysis also showed a
      significant elevation in the protein expression of ODC in the PCA tissues as
      compared with the paired benign tissue. Furthermore, our data showed that the ODC
      activity in the prostatic fluid obtained by a digital rectal massage from the
      patients with PCA (3847 +/- 162; mean +/- SE) was significantly higher than in
      the patients with benign prostatic hyperplasia (2742 +/- 167; mean +/- SE) or
      normal individuals (1244 +/- 67; mean +/- SE). This observation might be of
      significance because the prostatic fluid could be obtained noninvasively by
      digital rectal massage. We suggest that ODC could serve as a target for early
      detection of human PCA as well as for monitoring the efficacy of treatment(s).
      The development of ODC as a target for novel chemopreventive strategies against
      PCA is an intriguing possibility.

PMID- 9918213
TI  - Elevated levels of circulating plasma matrix metalloproteinase 9 in non-small
      cell lung cancer patients.
AB  - Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have
      been implicated as playing important roles in tumor invasion and metastasis in
      various tissues. We investigated the relationship between circulating plasma MMP
      9, its expression in tumor samples, and other clinical features in patients with
      non-small cell lung cancer (NSCLC). A series of 73 patients (45 men and 28 women)
      who underwent surgery for NSCLC was used in this study. Preoperative plasma
      concentrations of MMP-9 were examined using a one-step sandwich enzyme
      immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by
      immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0
      +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers
      (P < 0.0001). MMP-9 concentrations were elevated in 33 of 73 cases (45.2%),
      compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There
      were statistically significant differences in MMP-9 concentration in
      adenocarcinoma versus squamous cell carcinoma (P = 0.014) and adenocarcinoma
      versus large cell carcinoma (P = 0.014). Five of 24 patients (20.8%) had positive
      immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had
      positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations
      were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to
      correlate with MMP-9 production by cancer and stromal cells. We concluded that
      the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of
      NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

PMID- 9918214
TI  - Thrombospondins I and II messenger RNA expression in lung carcinoma: relationship
      with p53 alterations, angiogenic growth factors, and vascular density.
AB  - Thrombospondin (TSP) is a Mr 450,000 multifunctional matrix glycoprotein that
      interferes with tumor growth, angiogenesis, and metastasis. It has recently been
      shown that TSP expression is enhanced by the product of the p53 gene and that a
      down-regulation of TSP may be observed when alterations of the p53 protein occur.
      Moreover, a number of studies have demonstrated a regulatory activity of p53 on
      human vascular endothelial growth factor (VEGF), although additional
      investigations will be necessary to understand their relationship. In non-small
      cell lung carcinoma (NSCLC), neoangiogenesis, p53 alterations, and VEGF
      expression seem to have meaningful implications in the development and
      progression of this type of cancer. The aim of this study is to identify and
      quantitate TSP I and TSP II mRNA in NSCLCs with respect to p53 alterations,
      angiogenic growth factor expression, and microvascular density. A series of 24
      cases of NSCLC were analyzed. Eleven of 24 of the cases were positive for TSP II
      mRNA, whereas 8 of 24 showed TSP I mRNA expression. A significant inverse
      association was found between TSP I mRNA and fibroblast growth factor (FGF)
      protein expression (P = 0.00001). Tumors with low FGF protein expression (< or =
      40% of positive cells) presented a number of TSP I cDNA molecules, significantly
      higher than tumors expressing high levels of FGF protein. No association was
      found between TSP mRNA expression and other angiogenic growth factors (i.e.,
      VEGF) or tumoral neovascularization. On the contrary, tumors with high levels of
      FGF showed a higher number of microvessels (P = 0.05). By PCR-single-strand
      conformational polymorphism analysis, we observed aberrations of the p53 gene in
      19 of the 24 tumor samples. No association was found between p53 alterations and
      TSP mRNA expression. Instead, an interestingly significant association was found
      between the presence of p53 mutations and high VEGF protein expression (P = 0.01)
      and neovascularization (P = 0.03). Highly vascularized tumors showed higher VEGF
      protein expression (r = 0.45; P = 0.02). These data support the concept that in
      NSCLC, p53 exerts an important role in the control of neoangiogenesis. This
      influence is probably mediated by VEGF. The inverse association we found between
      TSP I and basic FGF suggests a different role of TSP I and TSP II in the
      angiogenic "switch," supporting the hypothesis that especially TSP I may have a
      significant function in tumor angiogenesis.

PMID- 9918215
TI  - Simultaneous protection of G156A methylguanine DNA methyltransferase gene
      transduced hematopoietic progenitors and sensitization of tumor cells using O6
      benzylguanine and temozolomide.
AB  - O6-Benzylguanine (BG) potentiates temozolomide (TMZ) cytotoxicity in tumors by
      inactivating O6-alkylguanine DNA alkyltransferase but also increases toxicity in
      hematopoietic cells. To improve the hematopoietic cell tolerance to alkylating
      agents, we retrovirally transduced the BG-resistant mutant G156A methylguanine
      DNA methyltransferase gene (deltaMGMT) into hematopoietic progenitors and
      evaluated whether deltaMGMT expression in hematopoietic colony-forming units
      would result in greater drug resistance to TMZ. DeltaMGMT expression in human and
      mouse colony-forming units followed by BG treatment resulted in a >7.7-fold
      increase in the TMZ 90% inhibitory concentration (IC90) and a 5.6-fold increase
      in the 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) IC90 relative to untransduced
      cells. This degree of protection enabled deltaMGMT-transduced CD34 cells to
      become much more resistant to BG and TMZ than SW480 cells, which express high O6
      alkylguanine DNA alkyltransferase and are normally resistant to TMZ or BCNU
      alone. DeltaMGMT-transduced long-term culture initiating cells were also
      resistant to the BG and TMZ combination, as were untransduced long-term culture
      initiating cells, suggesting that noncycling early progenitors may be partially
      protected from TMZ. These data indicate that retroviral transduction of deltaMGMT
      into hematopoietic progenitors followed by BG and TMZ treatment may selectively
      protect hematopoietic cells more efficiently than BCNU, allowing dose-intensive
      and repetitive therapy without the risk of cumulative myelosuppression.

PMID- 9918216
TI  - Without prior stimulation, tumor-associated lymphocytes from malignant effusions
      lyse autologous tumor cells in the presence of bispecific antibody HEA125xOKT3.
AB  - Women suffering from advanced stage ovarian or mammary carcinoma frequently
      develop malignant ascites or pleural effusions consisting of tumor cells and
      tumor-associated lymphocytes (TALs). Locoregional immunotherapy with bispecific
      antibodies (bsAbs), which retarget T cells to tumor cells and induce their lysis,
      has been applied as an adjuvant treatment in the late stage of the disease. Until
      now, most of these therapies use peripheral blood mononuclear cells (PBMCs) as
      effector cells that have been stimulated and expanded ex vivo and loaded with
      bsAb before reinjection. Here we investigated whether TALs derived from malignant
      ascites or pleural effusions can be used as bsAb-guided effector cells without
      prior in vitro stimulation. For this we established a bsAb, HEA125xOKT3, which
      recognizes the epithelial antigen Egp34 on carcinoma cells and the CD3 molecule
      on T cells. BsAb HEA125xOKT3 induced lysis of various Egp34-expressing carcinoma
      lines by stimulated PBMCs. Optimal cytotoxicity was achieved at a bsAb
      concentration of 1 microg/ml. In three ovarian and two mammary carcinoma
      patients, we demonstrated efficient lytic activity of lymphocytes, isolated from
      malignant ascites or pleural effusion. Without prior stimulation, they lysed
      autologous tumor cells in the presence of bsAb HEA125xOKT3, indicating that they
      are already activated. Along this line, a subset of CD4+ and CD8+ unstimulated
      TALs expressed the early activation marker CD69. They are, however, negative for
      CD95, and only a small subpopulation of CD4+ TALs expresses CD25.
      OKT3/interleukin 2 stimulation of TALs increased the expression of activation
      markers on the CD4+ and CD8+ T-cell compartment. The activation markers CD69,
      CD25, CD95, and DR molecules are up-regulated on both T-cell types. However,
      lysis of autologous tumor cells by stimulated TALs is not significantly enhanced
      compared with unstimulated TALs. Our results may offer a novel and promising
      concept of adjuvant immunotherapy for ovarian and mammary carcinoma patients.
      Preactivation and expansion of PBMCs can be circumvented by exploring the
      cytotoxic capacity of unstimulated TALs in the presence of bsAbs in a
      locoregional therapeutic approach.

PMID- 9918217
TI  - Antiangiogenic effects of camptothecin analogues 9-amino-20(S)-camptothecin,
      topotecan, and CPT-11 studied in the mouse cornea model.
AB  - Angiogenesis has been correlated with increased invasion and metastases in a
      variety of human neoplasms. Inadequate inhibition of the growth of tumor
      microvessels by anticancer agents may result in treatment failure, rated
      clinically as progressive or stable disease. We have investigated the
      antiangiogenic properties of three camptothecin analogues, 9-amino-20(S)
      camptothecin, topotecan, and camptosar (CPT-11), currently under investigation in
      clinical settings. Angiogenesis was induced by basic fibroblast growth factor in
      the cornea of inbred Swiss-Webster mice, with the aim of exploring the
      suppression of neovascularization by the analogues injected into the mice daily
      over a period of 6 days. The dose range chosen is known to inhibit, in the mouse
      model, the growth of various human tumor xenografts or murine tumors. The
      statistical analysis evaluated the association between the area of
      neoangiogenesis and the dose of the drugs tested and correlated the effects with
      observed drug toxicity. It was established that, as the drug doses increased, the
      area of neovascularization decreased, appearing to approximate a negative
      exponential curve. 9-Amino-20(S)-camptothecin at 6.89 and 8.26 micromol/kg (2.5
      and 3.0 mg/kg) and topotecan at 8.31 micromol/kg (3.5 mg/kg), both drugs being
      delivered over a 6-day period, had statistically significant reduction (47.2
      72.5%) of neoangiogenesis and acceptable toxicity. At higher doses of the two
      analogues, toxic body-weight losses and deaths were observed. CPT-11 showed
      statistically significant reduction of neoangiogenesis at a dose of 359
      micromol/kg (210 mg/kg) delivered over a 6-day course. Unlike camptothecin
      analogues, the nontoxic dose of vincristine did not induce a statistically
      significant inhibition of angiogenesis, and there was no dose-dependent
      escalation of antiangiogenic effects. The results indicate that camptothecins are
      most likely cytotoxic against two tumor compartments: in addition to tumor cells
      of epithelial origin, the drugs act against endothelial cells and prevent the
      growth of the tumor microvessels. We have hypothesized that treatment failure in
      some patients is due to incomplete or inadequate inhibition of the microvessel
      growth by camptothecins. Presumably, an intensive inhibition of the remaining
      tumor microvasculature in such patients could be achieved by combining a
      camptothecin with another antiangiogenic anticancer agent or with a highly
      selective angiogenic inhibitor exerting minimal dose-limiting toxicity. Such
      treatment by a camptothecin plus a less toxic inhibitor of angiogenesis can
      improve antitumor efficacy. To validate this concept, preclinical studies
      followed by clinical trials are planned.

PMID- 9918218
TI  - Interleukin 10 (IL-10) inhibition of primary human prostate cell-induced
      angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and
      inhibition of matrix metalloproteinase (MMP)-2/MMP-9 secretion.
AB  - In in vitro angiogenesis assays, aggregates of human papilloma virus (HPV)-18
      immortalized primary human prostate cancer cells (HPCA-5aHPV-18 or HPCA-10aHPV-18
      cells) induced human bone marrow endothelial cells (HBMCE-1 cells) to form
      microvessels in three-dimensional collagen I gels after 1-2 days incubation at 37
      degrees C. The microvessels aligned perpendicular to the tumor aggregates and
      abutted on the edges of the aggregates. The number and length of the microvessels
      increased significantly from day 1 to 2 (i.e., by approximately 30%). ELISAs
      showed that the HPCA-5aHPV-18 cells normally secreted low levels of tissue
      inhibitor of metalloproteinase (TIMP)-2, matrix metalloproteinase (MMP)-2, and
      MMP-9 but relatively high levels of TIMP-1. In contrast, HPCA-10aHPV-18 cells
      secreted high levels of MMP-2 and MMP-9 (>40 pg/microg protein) but low levels of
      TIMP-1 and TIMP-2 (<5 pg/microg protein). Interleukin 10 (IL-10) (15 ng/ml)
      induced TIMP-1 production (>15 pg/microg protein) but reduced MMP-2 and MMP-9
      secretion (<5 pg/microg protein) by the HPCA-5aHPV-18 and HPCA-10aHPV-18 cells.
      IL-10 (15 ng/ml) and MMP-9/MMP-2 antibodies all blocked induction of microvessel
      formation in the coculture experiments. In contrast, IL-10 receptor antibodies
      and TIMP-1 antibodies countered IL-10's effects and promoted angiogenesis. The
      data demonstrated that IL-10 stimulation of TIMP-1 and inhibition of MMP-2 and
      MMP-9 secretion by prostate tumor cells can control induction of angiogenesis in
      vitro.

PMID- 9918219
TI  - Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector
      sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3
      bis(2-chloroethyl)-1-nitrosourea and cisplatin.
AB  - Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is
      often overexpressed in human gliomas and that WAF1/Cip1 overexpression renders
      glioma cells resistant to chemotherapy agents. In this study, we investigated
      whether down-regulation of WAF1/Cip1 would sensitize gliomas to chemotherapy. An
      adenoviral vector expressing antisense WAF1/Cip1 was constructed and used to
      infect D54 glioma cells, which express a high level of endogenous WAF1/Cip1.
      After D54 cells were infected with antisense WAF1/Cip1 adenovirus, Western
      blotting revealed a significant decrease in the WAF1/Cip1 protein level. Down
      regulation of WAF1/Cip1 alone resulted in the cells rounding up and detaching
      from plates. Electron microscopy revealed some nuclear fragmentation in antisense
      WAF1/Cip1-infected cells, indicating the initiation of apoptosis. The antisense
      WAF1/Cip1-infected cells were then treated with the chemotherapeutic agents 1,3
      bis(2-chloroethyl)-1-nitrosourea and cisplatin. Other cells were infected with
      sense WAF1/Cip1 adenovirus or control virus and served as controls. Trypan blue
      exclusion assay revealed significant cell death in antisense WAF1/Cip1-infected
      cells. In situ end-labeling assay by flow cytometry revealed that many cells died
      of apoptosis. Our results show that the attenuation of WAF1/Cip1 expression
      initiated glioma cell death and sensitized glioma cells to apoptosis induced by
      1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Thus, blocking WAF1/Cip1
      production may serve as a useful chemosensitization regimen for treating glioma.

PMID- 9918221
TI  - Lack of evidence for a polymorphism at codon 160 of human O6-alkylguanine-DNA
      alkyltransferase gene in normal tissue and cancer.
AB  - O6-benzylguanine (BG) is a potent, specific inactivator of the DNA repair protein
      O6-alkylguanine-DNA alkyltransferase (AGT), which enhances sensitivity to
      nitrosoureas in cells and tumor-bearing animals. BG is presently undergoing
      clinical trials for development as an agent to enhance the therapeutic index of
      alkylating agent chemotherapy. It has been reported that a polymorphism exists in
      the human agt gene, with about 15% of the Japanese population having arginine at
      codon 160 instead of glycine on the polypeptide (Y. Imai et al., Carcinogenesis,
      16: 2441-2445, 1995). The resultant mutant AGT protein is equally effective
      against both methylated DNA as compared with wild type protein. However, this
      mutant AGT protein was less sensitive to inactivation by BG with a 20-fold
      increase in the ED50 value. This observation raised the possibility that a
      subpopulation of patients may be resistant to BG due to a single base change. We
      have demonstrated that this alteration also reduces the sensitivity to O6-benzyl
      8-oxoguanine, an equally potent, yet much longer-lived human metabolite of BG. To
      test the possibility that this germ-line mutation of the agt gene might explain
      resistance to BG and O6-benzyl-8-oxoguanine of patients on our Phase I clinical
      trials, we evaluated the DNA from lymphocytes of 18 patients. The G160R mutation
      was not found in any of the 18 patients. To determine the frequency of this
      mutation in the United States population, DNA from 181 healthy individuals were
      investigated and, again, the mutation was not observed in this cohort. Therefore,
      if the mutation exists, it is in statistically <1.6% of the United States
      noncancerous population. To investigate the possibility that this mutation might
      be somatic, we evaluated genomic DNA samples from 94 human primary cancers of
      four different histological subtypes (brain, colon, esophageal, and head and
      neck). Again, none were found to have the G160R mutation.

PMID- 9918220
TI  - Selective modulation of collagenase 1 gene expression by the chemotherapeutic
      agent doxorubicin.
AB  - Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and
      metastasis due to their ability to digest basement membrane and extracellular
      matrix components, thereby facilitating cell movement through connective tissues.
      At noncytotoxic concentrations, i.e., concentrations lower than those normally
      used in cancer chemotherapy, the anthracycline doxorubicin specifically inhibited
      collagenase 1 (MMP-1) gene expression in the highly invasive and metastatic human
      melanoma cell line A2058. This inhibition was specific for collagenase 1 because
      it did not affect the expression of two other MMPs, gelatinase A (MMP-2) and
      gelatinase B (MMP-9). The reduction in collagenase 1 expression correlated with a
      decrease in the invasive ability of tumor cells through a collagen type I matrix
      and was independent of the cytotoxic and antiproliferative effects usually
      associated with this anticancer drug. The selective modulation of collagenase 1
      expression by nontoxic doses of doxorubicin suggests a novel application for this
      chemotherapeutic agent, perhaps in combination therapy, because it decreases the
      invasive/metastatic potential of melanoma cells that are otherwise unaffected by
      this drug.

PMID- 9918222
TI  - Synergistic interaction between paclitaxel and 8-chloro-adenosine 3',5'
      monophosphate in human ovarian carcinoma cell lines.
AB  - Taxol is a unique anticancer agent that is used in treatment of advanced ovarian
      cancer. Taxol exposure results in the polymerization and stabilization of the
      microtubule skeleton of eukaryotic cells, hence blocking replication and
      intracellular motility. 8-Chloro-adenosine 3',5'-monophosphate (8-Cl-cAMP) is a
      cAMP analogue, currently in Phase II clinical trials, that displays growth
      inhibition at micromolar concentrations. The aim of this study was to assess the
      nature of the interaction between 8-Cl-cAMP and paclitaxel using the combination
      index (CI) method of Chou and Talalay, which uses the median-effect analysis. Two
      ovarian cancer cell lines, A2780 and OAW42, which differ in sensitivity to both
      drugs, were tested using the fixed-ratio design using various scheduling
      regimens. Concurrent exposure of both drugs resulted in highly synergistic
      interactions in both cell lines. CIs (mean +/- SE) with this schedule were 0.182
      +/- 0.016, 0.315 +/- 0.32, and 0.618 +/- 0.637 at 20, 50, and 80% cell kill,
      respectively, in A2780 cells and 0.001 +/- 0.0009, 0.016 +/- 0.0075, and 0.184 +/
      0.168 at 20, 50, and 80% cell kill, respectively, in OAW42 cells. In both cell
      lines, synergy was effective over a 4-fold log range of concentration for either
      drug. Sequencing with paclitaxel for 24 h prior to 8-Cl-cAMP was the most
      effective regimen; it resulted in consistently low CIs of up to the 90% cell kill
      level for both cell lines. Exposure to 8-Cl-cAMP prior to paclitaxel was the
      least effective regimen. In conclusion, the combination of paclitaxel and 8-Cl
      cAMP is highly synergistic in ovarian carcinoma cell lines, suggesting that 8-Cl
      cAMP may stimulate the antitumor effect of the taxanes.

PMID- 9918223
TI  - Thyroid hormones and estrogen affect oxytocin gene expression in hypothalamic
      neurons.
AB  - The oxytocin (OT) gene promoter has a composite hormone response element, such
      that several members of the steroid/thyroid hormone superfamily of nuclear
      receptors can interact at this response element in vitro. To investigate this in
      brain tissue, parallel to foregoing behavioural experiments, we used in situ
      hybridization histochemistry to seek interactions between estrogen and thyroid
      hormones on OT mRNA in the hypothalamus. In ovariectomized (OVX) rats, high doses
      of triiodothyronine (T3) elevated OT mRNA levels in the paraventricular (PVN)
      nucleus, while treatment with estradiol benzoate (EB) alone had no significant
      effect. In contrast, animals that were thyroidectomized (TX) in addition to OVX
      had dramatically elevated levels of OT gene expression in the PVN following EB
      treatment. That is, endogenous thyroid hormones interfered with EB-induction of
      gene expression. Moreover, in both OVX and TX/OVX animals, OT gene expression was
      reduced to values equivalent to controls when T3 was given together with EB.
      Particular subdivisions of the PVN responded differentially to T3 and EB
      treatment, demonstrating marked heterogeneity of OT-containing neurons in this
      nucleus. Thus, parallel to and perhaps related to the manner in which thyroid
      hormones reduced estrogen-stimulated behaviour, endogenous or exogenous thyroid
      hormones interfered with estrogen stimulation of OT mRNA. These data demonstrate
      competition between nuclear proteins, transcription factors, in hypothalamic
      neurons.

PMID- 9918224
TI  - Differential regulation of hippocampal glucocorticoid receptors mRNA and fast
      feedback: relevance to post-traumatic stress disorder.
AB  - Hippocampal glucocorticoid receptors (GR and MR) play an important role in
      glucocorticoid negative feedback. Abnormalities in negative feedback are found in
      depression and in post-traumatic stress disorder (PTSD), suggesting that GR and
      MR might be involved in the pathophysiology of these disorders. Enhanced negative
      feedback, the PTSD-specific neuroendocrine abnormality, can be induced in animals
      using a single prolonged stress (SPS) paradigm (a number of different stressors
      in one prolonged session, 'no stress' interval and a testing session one week
      later). In the current study, we examined hippocampal GR and MR mRNA distribution
      in the same animals that exhibited altered negative feedback following the SPS.
      Seven groups of adult Sprague-Dawley male rats (seven animals each) were used in
      two studies, comparing unstressed controls to acutely stressed animals (SPS: 24 h
      group), SPS animals (seven and 14 days), and SPS + chronic stress animals. GR and
      MR mRNA distribution across hippocampal subfields was studied using in-situ
      hybridization with 35S-labelled cRNA probes. Acute stress produced down
      regulation of GR and MR mRNA across all hippocampal subfields. Seven days later
      (SPS-7 group), there was a differential recovery, with GR mRNA reaching higher
      than the prestress levels, and MR mRNA remaining down-regulated. The same
      differential regulation was present in the 14-day group. Chronically stressed
      animals that exhibited normal fast feedback also had normalization in their GR
      and MR mRNA levels. The MR/GR ratio was decreased only in animals that had
      enhanced fast feedback. These findings suggest that the increase in GR, in
      hippocampus is involved in the fast feedback hypersensitivity observed in the SPS
      animals, and might also underlie enhanced dexamethasone sensitivity found in
      PTSD. Since differential activation of GR and MR can modulate memory, behavioural
      responsivity, anxiety and fear, change in MR/GR ratio might also explain other
      PTSD-related phenomena.

PMID- 9918225
TI  - Effect of intraseptal vasotocin and vasoactive intestinal polypeptide infusions
      on courtship song and aggression in the male zebra finch (Taeniopygia guttata).
AB  - The present experiments were conducted to test the hypothesis that septal
      arginine vasotocin (AVT) and vasoactive intestinal polypeptide (VIP) modulate
      directed song (a courtship behaviour) and aggression in male zebra finches
      (Taeniopygia guttata). Subjects were surgically fitted with a guide cannula
      directed at the septum. Following recovery they were tested for aggression and
      directed song following infusions of AVT, its antagonist (anti-vasopressin, AVP),
      and saline volume control. Infusion of the AVT antagonist significantly reduced
      all three aggressive behaviours measured (pecks, beak fences and chases); and AVT
      infusion significantly facilitated beak fencing. Vasoactive intestinal
      polypeptide treatment significantly reduced pecking. No treatment produced a
      change in directed song. Comparison with findings in mammals suggests that
      modulation of aggression by septal AVT (or AVP) is evolutionarily conserved in
      vertebrates, but modulation of aggression by VIP has not previously been reported
      for any vertebrate.

PMID- 9918226
TI  - Correlation of hypothalamic somatostatin mRNA expression and peptide content with
      secretion: sexual dimorphism and differential regulation by gonadal factors.
AB  - Sex differences in growth hormone (GH) secretion in the rat are thought to be
      determined, to a large extent, by gonadal steroid-dependent sex differences in
      somatostatin (SRIH) secretion from neurones in the periventricular nucleus (PeN)
      which project to the median eminence (ME). The present study aimed to obtain
      direct evidence for sex differences and gonadal regulation of SRIH release within
      this pathway and to determine the relationships between SRIH mRNA expression,
      SRIH peptide content and SRIH secretion in the adult rat. Somatostatin mRNA
      expression in the PeN and peptide content in both PeN and ME were higher in males
      than females (P<0.05). However, both basal and 56 mM K+-stimulated SRIH release
      in vitro from hypothalamic explants incorporating the PeN-ME pathway were higher
      (P<0.01) in females. The gonadectomy of female rats resulted in significantly
      reduced basal levels of SRIH release equivalent to that of males but had no
      effect on SRIH mRNA/peptide content or K+-stimulated release. In contrast,
      gonadectomy of male rats reduced SRIH mRNA and peptide contents and elevated K+
      stimulated secretion (P<0.01) to levels similar to that seen in intact females,
      without affecting basal release. In summary, these results demonstrate that in
      the PeN-ME of the adult rat: (1) SRIH mRNA and peptide content is well correlated
      and sexually dimorphic but dependent on gonadal factors in the male only; (2)
      SRIH secretion is sexually dimorphic and dependent on gonadal factors; but (3)
      differences in mRNA/peptide content do not reflect secretory capacity; and (4)
      gonadal factors differentially modulate SRIH secretory dynamics in males and
      females.

PMID- 9918227
TI  - Ontogeny and sexual differentiation of somatostatin biosynthesis and secretion in
      the hypothalamic periventricular-median eminence pathway.
AB  - The biosynthesis of somatostatin (SRIH) in the hypothalamic periventricular
      nucleus (PeN) is sexually differentiated in neonatal and adult rats by virtue of
      the organizational and activational actions, respectively, of sex steroid
      hormones. Little information exists, however, on the normal pattern of maturation
      of these neurones or on how the sexually differentiated biosynthesis may relate
      to ontogenetic changes in somatostatin secretion during the neonatal and pubertal
      periods of development. Hence in the present study we determined the postnatal
      developmental profile of SRIH mRNA and peptide levels in the PeN-median eminence
      (ME) pathway as well as SRIH secretion, using an acute explant preparation, from
      the day of birth, through puberty and into adulthood in male and female rats. The
      results demonstrate that: (1) developmental sex differences in SRIH biosynthesis
      in PeN neurones occurred in an orderly cascade with differences observed for mRNA
      expression at postnatal day 5, for peptide content in the perikarya at postnatal
      day 10 and for peptide content in the nerve terminal (ME) by postnatal day 25;
      (2) sex differences in SRIH release were not evident prior to postnatal day 40;
      and (3) the developmental profile of SRIH biosynthesis in PeN neurones is unique
      compared with other hypothalamic (ventromedial nucleus) and extrahypothalamic
      (parietal cortex) populations. Specific developmental changes in the biosynthetic
      and secretory activity of the hypothalamic SRIH PeN-ME pathway may have a
      functional importance in the maturation of hypothalamic SRIH pathways involved in
      the regulation of GH secretion.

PMID- 9918228
TI  - Glutamatergic induction of CREB phosphorylation and Fos expression in primary
      cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate
      activity of NMDA and non-NMDA receptors.
AB  - Exposure of Syrian hamsters to light 1 h after lights-off rapidly (10 min)
      induced nuclear immunoreactivity (-ir) to the phospho-Ser133 form of the
      Ca2+/cAMP response element (CRE) binding protein (pCREB) in the retinorecipient
      zone of the suprachiasmatic nuclei (SCN). Light also induced nuclear Fos-ir in
      the same region of the SCN after 1 h. The glutamatergic N-methyl-D-aspartate
      (NMDA) receptor blocker MK801 attenuated the photic induction of both factors. To
      investigate glutamatergic regulation of pCREB and Fos further, tissue blocks and
      primary cultures of neonatal hamster SCN were examined by Western blotting and
      immunocytochemistry in vitro. On Western blots of SCN tissue, the pCREB-ir signal
      at 45 kDa was enhanced by glutamate or a mixture of glutamatergic agonists (NMDA,
      amino-methyl proprionic acid (AMPA), and Kainate (KA)), whereas total CREB did
      not change. Glutamate or the mixture of agonists also induced a 56 kDa band
      identified as Fos protein in SCN tissue. In dissociated cultures of SCN,
      glutamate caused a rapid (15 min) induction of nuclear pCREB-ir and Fos-ir (after
      60 min) exclusively in neurones, both GABA-ir and others. Treatment with NMDA
      alone had no effect on pCREB-ir. AMPA alone caused a slight increase in pCREB-ir.
      However, kainate alone or in combination with NMDA and AMPA induced nuclear pCREB
      ir equal to that induced by glutamate. The effects of glutamate on pCREB-ir and
      Fos-ir were blocked by antagonists of both NMDA (MK801) and AMPA/KA (NBQX)
      receptors. In the absence of extracellular Mg2+, MK801 blocked glutamatergic
      induction of Fos-ir. However, the AMPA/KA receptor antagonist was no longer
      effective at blocking glutamatergic induction of either Fos-ir or pCREB-ir,
      consistent with the model that glutamate regulates gene expression in the SCN by
      a co-ordinate action through both NMDA and AMPA/KA receptors. Glutamatergic
      induction of nuclear pCREB-ir in GABA-ir neurones was blocked by KN-62 an
      inhibitor of Ca2+/Calmodulin (CaM)-dependent kinases, implicating Ca2+-dependent
      signalling pathways in the glutamatergic regulation of gene expression in the
      SCN.

PMID- 9918229
TI  - Changes in NADPH-d staining in the paraventricular and supraoptic nuclei during
      pregnancy and lactation in rats: role of ovarian steroids and oxytocin.
AB  - Staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a
      histochemical marker for nitric oxide synthase (NOS), is increased in the
      supraoptic (SON) and paraventricular (PVN) nuclei in late pregnant rats. To
      determine whether increases in staining were evident at other times during
      pregnancy and lactation the number of cells that stained for NADPH-d in the SON
      and PVN in rats on days 4, 12, 16, and 22 of pregnancy and on days 4, 12, and 20
      of lactation was compared to that in virgin females. In a second experiment the
      influence of ovarian hormones on NADPH-d staining was assessed by comparing
      staining in the SON and PVN among ovariectomized animals exposed to either a
      steroid hormone replacement schedule that mimics late pregnancy (oestrogen and
      progesterone with progesterone removal), oestrogen alone, oestrogen and
      progesterone, or cholesterol alone. In the last experiment of this series
      staining was compared among ovariectomized animals given either oestrogen or
      cholesterol priming accompanied by oxytocin (OT) or vehicle infusion into the
      third ventricle for 7 days. The number of cells showing dense staining for NADPH
      d in both the SON and PVN increased on days 12 and 22 of pregnancy and 4 and 12
      of lactation compared to that observed in virgins. NADPH-d staining in these
      areas was also increased by both the steroid treatment that mimicked late
      pregnancy and chronic central OT infusion in oestrogen-primed animals. These data
      suggest that NADPH-d staining in the SON and PVN is increased at times when
      oxytocinergic cells are known to be active and that the hormonal state associated
      with late pregnancy is sufficient to increase NADPH-d staining.

PMID- 9918230
TI  - Serotonergic 5-HT2A receptors important for the oestradiol-induced surge of
      luteinising hormone-releasing hormone in the rat.
AB  - Serotonin (5-HT) plays a role in mediating the oestradiol-induced surge of
      luteinising hormone (LH), but so far the 5-HT receptor subtype involved has not
      been identified. Our previous in-situ hybridization and pharmacological studies
      suggest that the action of 5-HT involves the 5-HT2A receptor. The aim of the
      present study was to investigate this possibility by the direct approach of
      determining whether 5-HT2A receptor antagonists block the oestradiol-induced
      surge of luteinising hormone releasing hormone (LHRH). Adult female Wistar rats,
      which had shown at least two consecutive 4-day oestrous cycles, were
      ovariectomised under halothane anaesthesia in the morning of dioestrus and
      injected with vehicle (arachis oil) alone or oestradiol benzoate (OB). At 12.00 h
      of the next day, presumptive pro-oestrus, the animals were injected
      intraperitoneally with one of three 5-HT2A antagonists, a selective 5-HT reuptake
      inhibitor (fluoxetine), or the appropriate vehicles; hypophysial portal blood was
      then collected under alphaxalone anaesthesia between 15.00 and 19.00 h. The
      amount of LHRH released into hypophysial portal blood during consecutive 30-min
      periods was determined by radioimmunoassay. As expected, oestradiol, but not oil,
      triggered a surge of LHRH in hypophysial portal blood with a peak at about 16.00
      h of presumptive pro-oestrus. This oestradiol-induced surge of LHRH was blocked
      by ketanserin, ritanserin and the highly selective 5-HT2A receptor antagonist,
      RP62203, but not by fluoxetine. These results provide the first direct evidence
      that the 5-HT2A receptor plays an important role in the oestradiol-induced surge
      of LHRH.

PMID- 9918231
TI  - Corticotropin-releasing factor but not urocortin is involved in adrenalectomy
      induced adrenocorticotropin release.
AB  - Urocortin, a new corticotropin-releasing factor (CRF)-related peptide, has been
      reported to have the ability to bind to CRF receptors and to stimulate
      adrenocorticotropin (ACTH) secretion from the rat anterior pituitary in vivo and
      in vitro. In this study, we examined the effect of intravenous administration of
      urocortin-antiserum to investigate the role of endogenous urocortin on ACTH
      secretion from rat anterior pituitary after adrenalectomy. Male Sprague-Dawley
      rats, which were maintained in a conscious and undisturbed condition, were
      administered non-immunized rabbit serum (NRS), CRF-antiserum or urocortin
      antiserum at a volume of 1 ml/kg b.w. 15 min before the injection of
      secretagogues. Synthetic rat urocortin (2 microg/kg B.W.) increased plasma ACTH
      concentrations by about sixfold the basal concentration. The pretreatment with
      urocortin-antiserum but not CRF-antiserum abolished the urocortin-induced
      increase in plasma ACTH concentrations. In adrenalectomized rats, plasma ACTH
      concentrations were markedly increased at basal conditions, and rapidly reduced
      after the administration of CRF-antiserum. By contrast, administration of
      urocortin-antiserum did not alter ACTH secretion induced by adrenalectomy. Our
      results suggest that endogenous urocortin is unlikely to be involved in ACTH
      release in adrenalectomized rats.

PMID- 9918232
TI  - Does smoking cause rheumatoid arthritis?

PMID- 9918233
TI  - Evaluation of functional capacity in ankylosing spondylitis.

PMID- 9918234
TI  - Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult
      rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate in various groups of patients with chronic joint disease
      the sensitivity and specificity of anti-Sa antibody, recently described in sera
      from adults with rheumatoid arthritis (RA); and to determine the prognostic
      significance of anti-Sa in initial sera from patients with long standing RA with
      or without severe joint destruction. METHODS: Serum samples from 489 patients
      were included. Of these, 154 were collected from patients with RA attending 2
      rheumatology units. Controls were 335 patients with a variety of inflammatory
      joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting
      method with purified Sa antigen from human placenta extracts. All patients were
      tested for the following antibodies: rheumatoid factor (RF), anti-keratin
      antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB
      alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera
      overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from
      the recent onset RA group (p<0.01). In patients with long standing RA,
      statistically significant associations were found between the presence of anti-Sa
      and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and
      HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33.
      Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients
      with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was
      92.1% in adults with well characterized rheumatic diseases and 85.9% in adults
      and children together. Among patients with long standing RA, those with
      destructive disease were more likely to test positive for anti-Sa (66.6%) than
      those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other
      serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was
      also the test with the highest specificity (79%), positive predictive value
      (75%), and negative predictive value (71%) for discriminating between patients
      who do and those that do not develop late severe radiographic damage. CONCLUSION:
      Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients
      with severe radiographic damage.

PMID- 9918235
TI  - Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells.
AB  - OBJECTIVE: To investigate the immunosuppressive mechanism of Tripterygium
      wilfordii Hook-F (TWHf) in human T cells. TWHf, a traditional Chinese medicinal
      herb for rheumatoid arthritis, has been shown to inhibit the function of immune
      effector cells such as neutrophils, macrophages, and B lymphocytes. METHODS: T
      cell survival was evaluated with trypan blue exclusion assay, morphologic changes
      with Wright's stain, the induction of endonuclease activity with DNA
      fragmentation assay, and the subdiploid DNA content with flow cytometry. T cell
      activation was measured with interleukin 2 (IL-2) ELISA and the expression of
      several surface molecules with flow cytometry. RESULTS: At high dosages, TWHf
      caused inhibition of T cell proliferation and this mechanism was mediated through
      the induction of apoptosis. TWHf, in noncytotoxic dosages, was as potent as
      cyclosporin A and more potent than prednisolone and cyclophosphamide in
      inhibiting IL-2 production from activated T cells. TWHf also inhibited both
      phorbol 12-myristate 13-acetate induced IL-2Ralpha expression and ionomycin
      induced CD40 ligand expression. TWHf did not reverse downregulated expression of
      CD3 and CD4 by phorbol ester stimulation. CONCLUSION: This is the first evidence
      that the immunosuppressive mechanism of TWHf in T cells was mediated through both
      downregulation of T cell receptor signaling pathway and induction of cellular
      apoptosis, which is defective in autoimmune diseases.

PMID- 9918236
TI  - Effects of actarit on synovial cell functions in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Actarit (4-acetylaminophenylacetic acid), developed in Japan, has been
      shown to be effective for suppressing disease activity of rheumatoid arthritis
      (RA). We analyzed effects of actarit on synovial cell functions in patients with
      RA for insight into the clinical application of this medication. METHODS: RA
      primary synovial cells were co-cultured with actarit at 10(-4)-10(-7) M. Their
      subsequent proliferative responses and proinflammatory cytokine and matrix
      metalloproteinase (MMP) production at the mRNA and protein levels were measured.
      Effects of actarit on adhesion molecule expression were analyzed by
      immunofluorescence flow cytometry and cell-cell binding assay. RESULTS:
      Spontaneous tumor necrosis factor-alpha and interleukin 1beta secretion by
      primary synovial cells of patients with RA was reduced by actarit at therapeutic
      concentrations (10(-5)-10(-6) M). In contrast, actarit also suppressed MMP-1
      production by the primary synovial cells. In addition, actarit down-regulates
      CD44 and intercellular adhesion molecule 1 expression on fibroblast-like synovial
      cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial
      cells resulted in the inhibition of lymphocyte adhesion to RA synovial cells.
      CONCLUSION: The results suggest that actarit acts on RA synovial cells to reduce
      cell-cell interactions with autologous synovium infiltrating lymphocytes and to
      inhibit proinflammatory cytokine and MMP production, leading to amelioration of
      symptoms of RA.

PMID- 9918237
TI  - Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and
      glycosaminoglycans in synovial fluid from patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the correlation between synovial fluid (SF)
      concentrations of metalloproteinase (MMP) -2, -3, and -9, tissue inhibitors of
      metalloproteinases (TIMP)-1 and -2, chondroitin 4-, 6-sulfate (deltadi-C4S,
      deltadi-C6S), hyaluronic acid (deltadi-HA), antigenic keratan sulfate (KS), and
      radiologic grade in patients with rheumatoid arthritis (RA) and to assess the
      clinical value of these factors as disease markers. METHODS: Enzyme linked
      immunoassays and high performance liquid chromatography were used. SF samples
      were collected from 52 patients with RA. Radiographic (Larsen grade) and clinical
      evaluations were also done. RESULTS: There was no significant correlation between
      the concentrations of MMP, TIMP, and deltadi-C4S, deltadi-C6S, deltadi-HA, and
      antigenic KS. No significant correlations were found between the radiologic grade
      and the concentrations of MMP or TIMP in SF. There was a significant increase in
      the concentration of antigenic KS and deltadi-C6S/deltadi-C4S ratio in SF from
      patients with Larsen grade 2 compared to grade 5. A significant correlation
      between deltadi-C6S and antigenic KS concentrations in SF was observed.
      CONCLUSION: Although there were large variances between the samples in this
      study, proteoglycan metabolism in the cartilage matrix of the patients with RA
      might have been increased in the early phases of tissue destruction and decreased
      in advanced stages because of scanty cartilage tissue. The concentrations of MMP
      2, -3, -9 and TIMP-1, -2 in SF did not seem to be influenced by the amount of
      residual cartilage.

PMID- 9918238
TI  - Evaluation of surgeries for rheumatoid shoulder based on the destruction pattern.
AB  - OBJECTIVE: To identify the optimal treatment of rheumatoid shoulder, we analyzed
      the clinical results of shoulder surgeries according to each type of shoulder
      destruction pattern. METHODS: Forty-seven shoulder surgeries for rheumatoid
      arthritis (18 arthroscopic synovectomies, 10 total shoulder replacements, 19
      humeral head replacements) were assessed clinically and compared in regard to 5
      different destruction patterns of rheumatoid shoulder (nonprogressive, arthrosis
      like, erosive, collapse, and mutilating patterns). RESULTS: For nonprogressive
      type shoulders, we were able to obtain both pain relief and range of motion (ROM)
      improvement with arthroscopic synovectomy. For erosive-type shoulders, we could
      obtain pain relief but no ROM improvement with synovectomy; and we obtained both
      pain relief and ROM improvement with prosthetic replacement. For the collapse
      type shoulders, we could not obtain pain relief or ROM improvement with
      arthroscopic synovectomy, but did obtain pain relief with prosthetic replacement.
      For mutilating-type shoulders, we could obtain only pain relief with prosthetic
      replacement. The results of the various surgeries for rheumatoid shoulder were
      distinctly different depending on the shoulder destruction patterns. CONCLUSION:
      These findings could be of value for the selection of treatment, including a
      surgical procedure, for rheumatoid shoulders. For the nonprogressive-type and for
      erosive-type shoulders before bone destruction progresses, arthroscopic
      synovectomy should be selected. For erosive-type shoulders after bone
      destruction, for the collapse-type, and for mutilating-type shoulders, prosthetic
      replacement should be selected. In regard to the prosthetic replacement, the
      humeral component should be cemented because the incidence of migration in
      noncemented humeral component procedures was high.

PMID- 9918239
TI  - Current tobacco smoking, formal education, and the risk of rheumatoid arthritis.
AB  - OBJECTIVE: To identify if tobacco smoking or sociodemographic characteristics are
      risk factors of rheumatoid arthritis (RA). METHODS: From a county RA register 361
      patients in the age range 20-79 years were recruited from incidence cohorts with
      recent disease onset (mean 3.4 years) and compared with 5851 randomly selected
      individuals from the same population area. Data on selected risk factors were
      collected by questionnaires (response rate 75 and 59%, respectively) and
      associations with smoking and risk factors were expressed as odds ratios (OR)
      with 95% confidence intervals (CI) in a multiple regression analysis. RESULTS:
      Age and female sex were, as expected, identified as risk factors of RA. In
      addition, current smoking was an overall risk factor (OR 1.46, 95% CI 1.10-1.94),
      in men (OR 2.38, 95% CI 1.45-3.92), especially in men with seropositive RA (OR
      4.77, 95% CI 2.09-10.90). Separate analyses revealed no statistically significant
      risk in women (OR 1.14, 95% CI 0.80-1.62). Low level of formal education, body
      mass index, marital or employment status were not significantly associated with
      risk of RA. CONCLUSION: Current smoking in men was identified as an independent
      risk factor for RA, whereas surrogate markers of socioeconomic status were
      unrelated to the onset of RA.

PMID- 9918240
TI  - Association between prolactin and disease activity in systemic lupus
      erythematosus. Influence of statistical power.
AB  - OBJECTIVE: To analyze the statistical power of studies in the medical literature
      on the relationship between prolactin (PRL) and systemic lupus erythematosus
      (SLE) activity. METHODS: Published studies that were identified through MEDLINE
      search, as well as references from these articles, were reviewed. RESULTS: We
      identified 5 articles that sought to establish a relationship between PRL and SLE
      activity. In 4 of them, the frequency of hyperprolactinemia in SLE (>20 ng/ml)
      was 2.2-47.2%, and in one article, there was a relationship between PRL and SLE
      activity. A power analysis of individual studies could be carried out in only 2
      of the 5; there were no significant effects; the 2 articles cited differences in
      the frequency of hyperprolactinemia in patients with and without lupus activity
      (1.6 and 12.3%, respectively), but because of a low power of the studies (> or
      =30.8%), it could not be determined whether the differences in the frequency of
      hyperprolactinemia were significant. On the other hand, joint analysis of 3
      articles showed a significant association between hyperprolactinemia and lupus
      activity. CONCLUSION: Published clinical results concerning the relationship
      between PRL and Jupus activity are contradictory, due in part to the statistical
      power of the studies. Our analysis of these studies showed that PRL is related to
      lupus activity, without establishing a formal causal relationship.

PMID- 9918241
TI  - Patients with systemic lupus erythematosus with high plasma levels of sFas risk
      relapse.
AB  - OBJECTIVE: We related soluble Fas (sFas) levels to the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) in a longitudinal series of plasma
      samples of patients with SLE to evaluate the relation between excessive
      production of sFas and disease activity. METHODS: We generated 21 monoclonal
      antibodies against Fas. Two of these were used to develop and validate a
      sensitive sandwich ELISA for the longitudinal analysis of sFas levels in plasma
      of 30 patients and 25 controls. RESULTS: At the start of followup, a significant
      elevation (p<0.0001) was found in sFas levels in SLE (1167+/-347 pg/ml sFas)
      compared to controls (618+/-98 pg/ml sFas). Also, at the start of the followup a
      significant difference (p = 0.0028) existed between patients who were going to
      have a relapse (1236+/-402 pg/ml sFas) during followup and patients who were not
      (809+/-276 pg/ml sFas). While sFas did not fluctuate with disease activity in
      individual patients, we found a strong correlation (r = 0.75, p<0.0001) between
      sFas and SLEDAI, but only at the time of relapse, when we analyzed the patients
      as a group. CONCLUSION: In individual patients with SLE, sFas does not fluctuate
      with disease activity. However, patients with high plasma levels of sFas are at
      risk of relapse.

PMID- 9918242
TI  - Lupus panniculitis: clinical perspectives from a case series.
AB  - OBJECTIVE: To review clinical and laboratory features of lupus panniculitis from
      a large group of patients. METHODS: Retrospective chart review of patients
      diagnosed with lupus panniculitis at a tertiary medical center from 1976 to 1993.
      RESULTS: Lupus panniculitis occurred most frequently in adult women. Skin lesions
      involved proximal extremities, trunk, face, and scalp. Only 4 of 40 patients
      fulfilled criteria for systemic lupus erythematosus (SLE), and, other than
      positive antinuclear antibodies, a paucity of other autoantibodies was seen.
      Average disease duration was 6 years (range 0-38). Treatment with antimalarial
      agents was undertaken in most cases. Disease related morbidity (disfigurement and
      disability) was relatively common, but death was rare. CONCLUSION: Lupus
      panniculitis is a chronic inflammatory disease of subcutaneous adipose tissue
      that can develop during the course of SLE, although most patients do not develop
      systemic lupus.

PMID- 9918243
TI  - A comparison of autoantibody production in asymptomatic and symptomatic women
      with silicone breast implants.
AB  - OBJECTIVE: We previously reported an increased preponderance of a broad range of
      autoantibodies in symptomatic women with silicone breast implants. The objective
      of this study was to investigate the frequency of autoantibody production in
      asymptomatic compared to symptomatic women with silicone implants. One hundred
      twenty-two asymptomatic women were recruited to our center for autoantibody
      detection through an advocate dealing with breast implant liabilities. METHODS:
      Autoantibody detection in 86 asymptomatic women was done blindly on a panel of 15
      different antibodies (dsDNA, ssDNA, histones, SSA/Ro, SSB/La, RNP, cardiolipin,
      phosphatidylserine, pyruvate dehydrogenase, Scl-70, NC-1, silicone, collagen I,
      II, and IV). Clinical variables, specific questioning about related silicone
      implant symptoms, and a rheumatological examination were performed blindly by a
      certified rheumatologist. The findings were recorded and at a later stage
      compared with positive autoantibody detection. The normal control group consisted
      of age and sex matched Israeli women without known autoimmune disease. In the
      positive control group were symptomatic women previously tested for antibody
      production. The autoantibodies were assessed by ELISA. Values from individual
      patients were considered positive only when greater than 3 standard deviations
      above the control mean. RESULTS: The mean ages of 86 asymptomatic and 116
      symptomatic women were 46.2+/-11.2 and 45.7+/-8.3 years, respectively. Breast
      implants were in place for a mean period of 8.2+/-5.0 years in the asymptomatic
      group and 15.0+/-5.6 years in the symptomatic group. The incidence of increased
      titers of autoantibodies ranged from 2 to 13% for 13 different autoantibodies
      among asymptomatic women. Among symptomatic women, 20% harbored 4 autoantibodies
      and 8% had 6 autoantibodies. The most common antibodies in the asymptomatic group
      were: dsDNA 8%; ssDNA 9%; SSB/La 13%; silicone 9%; collagen II 9%. No
      autoantibodies were found for NC-1, Scl-70, or RNP. Among the symptomatic group,
      the most common autoantibodies were histone ribosomal phosphate, SSA, SSB, Scl
      70, cardiolipin, phosphatidylserine, GM2-ganglioside, and NC-1. Comparison of
      autoantibody incidence in asymptomatic and symptomatic women with silicone breast
      implants revealed an increased incidence of anti-SSB/La and anticollagen II in
      both groups. Polyclonality was more prominent in the group of symptomatic women
      with silicone breast implants, but also evident in 3 asymptomatic women.
      CONCLUSION: The mean duration of implant in the asymptomatic group was
      significantly less compared with the symptomatic group (p<0.01). The development
      of autoantibodies may be related to implant duration.

PMID- 9918244
TI  - Increased serum stromelysin-1 levels in systemic lupus erythematosus: lack of
      correlation with disease activity.
AB  - OBJECTIVE: In view of evidence that stromelysin-1 and collagenase-1 are involved
      in tissue injury in inflammatory joint diseases, we sought to determine whether
      matrix metalloproteinases (MMP) are implicated in the pathophysiology of systemic
      lupus erythematosus (SLE). METHODS: Seventy-three patients with SLE and 39
      healthy subjects were evaluated. Serum levels of MMP and tissue inhibitor of
      metalloproteinases were measured. RESULTS: Serum stromelysin-1 levels were
      significantly increased in patients with SLE (416+/-252 ng/ml) compared to
      healthy subjects (125+/-93 ng/ml). No correlation between serial measurements of
      stromelysin-1 and disease activity in SLE patients was noted. Serum collagenase
      1, gelatinase A, and TIMP-1 levels were not increased in SLE. CONCLUSION: Serum
      concentrations of stromelysin-1 are increased in SLE, but the levels do not
      correlate with disease activity.

PMID- 9918245
TI  - Relationship between neurometabolite derangement and neurocognitive dysfunction
      in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the relationship between neurochemical markers of brain
      injury and brain dysfunction associated with systemic lupus erythematosus (SLE).
      METHODS: Patients with SLE (n = 12) were studied using magnetic resonance
      spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a
      neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate
      (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white
      (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and
      Cho/Cre. Neurocognitive testing results were expressed as a composite z score.
      Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and
      disease injury by Systemic Lupus International Collaborating Clinics
      (SLICC)/American College of Rheumatology Damage Index. RESULTS: Neurochemical
      measures of brain injury were correlated with neurocognitive testing z scores:
      NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also
      correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and
      SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71,
      p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between
      neurometabolite ratios and SLEDAI did not reach significance. CONCLUSION: Brain
      function is closely correlated with brain injury assessed noninvasively by proton
      magnetic resonance spectroscopy. This important finding further supports the use
      of magnetic resonance spectroscopy to evaluate brain injury in SLE.

PMID- 9918246
TI  - Distribution of lupus anticoagulant and anticardiolipin antibody isotypes in a
      population with antiphospholipid syndrome.
AB  - OBJECTIVE: To analyze the distribution of lupus anticoagulant (LAC) and
      anticardiolipin antibody (aCL) isotypes in a population with antiphospholipid
      syndrome and to explore whether there is an association with the site of
      thrombotic episodes and the number of recurrent spontaneous abortions. METHODS:
      Ninety-two patients (73 female, 19 male) with positive LAC and/or aCL were
      included as 2 groups: (1) 20 patients with secondary antiphospholipid syndrome
      (APS) (16 had thrombotic episodes and 4 thrombocytopenia); (2) 72 patients with
      primary APS (31 presented thrombotic episodes and 41 had recurrent spontaneous
      abortion). RESULTS: In Group 1 seven of 20 (35%) patients with secondary APS had
      IgG aCL, 9 (45%) had both IgG/IgM aCL, and 2 (10%) had IgM aCL; the remaining
      patients had combinations of aCL isotypes. In Group 2 patients with primary APS,
      IgG aCL was positive in 41%, IgG/IgM mixture in 21%, and 15% of patients had
      combinations of the 3 isotypes. Sixteen of 20 (80%) patients with secondary
      disease and 37 of 72 (51%) with primary disease tested positive for LAC.
      CONCLUSION: The presence of one or any mixture of isotype of aCL with or without
      LAC is not associated with the site of thrombosis (venous or arterial). On the
      contrary, in the patients with primary APS, the presence of the 3 aCL isotypes
      plus LAC was associated with a higher number of recurrent spontaneous abortions
      compared to other possible combinations of aCL isotypes.

PMID- 9918247
TI  - Longitudinal determination of antiphospholipid antibodies in lupus patients
      without previous manifestations of antiphospholipid syndrome. A prospective
      study.
AB  - OBJECTIVE: To investigate whether serial anticardiolipin determination
      contributes to the clinical management of patients with systemic lupus
      erythematosus (SLE) with no previous sign of the antiphospholipid syndrome (APS).
      METHODS: In 90 patients with SLE with no previous clinical manifestations of the
      APS, repeated clinical evaluations were performed, and serial blood samples
      (obtained over a 30 month period, range 13-53 mo) were screened for
      antiphospholipid antibodies (aPL). Anticardiolipin antibodies (aCL) were detected
      using an ELISA and considered positive if the result was >25 GPL on 2 separate
      occasions. Patients were not required to be on a specific treatment regimen
      during the study. RESULTS: Thirty-four patients (37%) had at least one positive
      ELISA and 11 (11/90, 12%) 2 positive ELISA for IgG aCL during the study. Lupus
      anticoagulant (LAC) was found in 16 patients, and a false positive VDRL in 5. At
      study completion, the total number of clinical or laboratory events associated
      with APS was 30. In univariate analysis, aCL was significantly associated only
      with LAC (p<0.012). Presence of aCL also correlated with hemoglobin level, anti
      DNA antibody, leukocyte count, and the SLE Disease Activity Index (SLEDAI). LAC
      and aCL were significantly associated with each other (OR 5.17; 95% CI 1.5-17.7),
      but LAC had a better positive predictive value than aCL for arterial thrombosis
      and neurological events. CONCLUSION: Among our patients with SLE without previous
      clinical manifestations of APS, positive aCL did not predict the occurrence of
      APS within the next 3 years, but was statistically related to the clinical
      disease activity (SLEDAI).

PMID- 9918248
TI  - Validation of the MOS SF-36 for quality of life assessment of patients with
      systemic lupus erythematosus in Singapore.
AB  - OBJECTIVE: To assess the reliability and construct validity of the Medical
      Outcomes Study Short Form 36 Health Survey (SF-36) in a multiracial cohort of
      Asian patients with lupus in Singapore. METHODS: A cross sectional study was
      performed on 118 English speaking patients with lupus attending a specialist
      rheumatology unit between March and August 1996. Patients completed a
      questionnaire containing the UK standard version of the SF-36 twice within a 14
      day period. All patients were assessed for disease activity using the British
      Isles Lupus Assessment Group score (BILAG), and for disease related damage using
      the Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (SLICC/ACR) damage index (DI). Relationships between SF-36, BILAG,
      and DI scores were studied using Spearman's rank correlation. Internal
      consistency of the SF-36 was assessed using Cronbach's alpha, and stability using
      the repeatability coefficient of Bland and Altman. RESULTS: SF-36 subscales
      showed high internal consistency, with Cronbach's alpha coefficient ranging from
      0.84 to 0.94. Test-retest reliability was acceptable, with Spearman's rank
      correlation >0.70 for all subscales except role-physical, and mean differences in
      test scores of <2 points for 5 of 8 subscales. SF-36 subscale scores were weakly
      correlated with BILAG scores (Spearman's p -0.37 to 0.15) and SLICC/ACR DI scores
      (Spearman's p -0.25 to 0.23), suggesting divergent construct validity of the SF
      36. CONCLUSION: These data suggest the SF-36 is a reliable and valid measure of
      the quality of life of patients with lupus in Singapore.

PMID- 9918249
TI  - Lymphocyte activation markers and von Willebrand factor antigen in Wegener's
      granulomatosis: potential markers for disease activity.
AB  - OBJECTIVE: To examine 3 soluble circulating T cell antigens: interleukin 2
      receptors (sIL-2r), CD4 (sCD4), and CD8 (sCD8) with von Willebrand factor antigen
      levels (vWF:Ag) and antiendothelial cell antibodies (AECA) as indices of
      endothelial involvement in patients with Wegener's granulomatosis (WG). METHODS:
      We studied 23 patients with WG, of whom 11 had active disease with renal
      involvement, and 20 healthy controls. sIL-2r, sCD4, sCD8, vWF:Ag, and AECA were
      measured by ELISA. RESULTS: Median sIL-2r levels in patients were higher than
      controls (789.5 vs. 551 U/ml, p<0.01). sCD4 levels were higher in patients: 17.0
      vs. 15.2 U/ml (p<0.005) and correlated with sIL-2r levels. sIL-2r and sCD4 levels
      correlated with disease activity scores, antineutrophil cytoplasmic antibodies
      (ANCA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and
      neutrophil counts. sCD8 levels were also higher: 260.5 vs. 127 U/ml (p<0.001) and
      correlated with CRP levels but not with disease activity. vWF:Ag levels were
      elevated in patients (median 296% vs. controls 109%; p<0.001) and correlated with
      disease activity, ESR, CRP, ANCA titers, and serum creatinine levels. AECA levels
      did not differ from controls (5% vs. 7%). CONCLUSION: Circulating levels of sIL
      2r, sCD4, sCD8, and vWF:Ag are elevated in active WG, indicating T cell and
      endothelial activation. sIL-2r, sCD4, and vWF:Ag are potentially useful disease
      activity markers.

PMID- 9918250
TI  - Oral microbial flora in Sjogren's syndrome.
AB  - OBJECTIVE: To study presence of microorganisms associated with caries,
      gingivitis, oral opportunistic infections, and extent of hyposalivation in
      dentate patients with primary and secondary Sjogren's syndrome (SS). METHODS: An
      oral clinical examination was performed. The salivary flow was measured and a
      rinsing sample analyzed for presence of specific microorganisms. The results were
      compared to those of healthy controls matched for sex, age, and number of teeth.
      RESULTS: In patients with undetectable salivary flow at rest, mean number and
      proportion of mutans streptococci and lactobacilli showed a tendency to be
      increased, as well as the frequency of Candida. They also displayed an increased
      proportion of filled surfaces. In contrast, gingivitis and the numbers of
      microorganisms associated with gingivitis were comparable to those found in the
      healthy controls. CONCLUSION: Patients with SS and severe hyposalivation harbor
      oral flora associated with the development of caries and frequent presence of
      retention sites, indicating a need for efficient preventive dental care.

PMID- 9918252
TI  - Validity and sensitivity to change of spondylitis-specific measures of functional
      disability.
AB  - OBJECTIVE: To compare the construct validity and sensitivity to change of 2
      spondylitis-specific measures of functional disability, the Health Assessment
      Questionnaire Disability Index modified for the spondyloarthropathies (HAQ-S) and
      the Dougados Functional Index, with 2 more generic instruments, the Health
      Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales-2
      (AIMS2), in patients with ankylosing spondylitis (AS). METHODS: Construct
      validity was assessed in 2 ways: (1) by comparisons of the cross sectional
      correlations between each functional disability instrument and 6 measures of
      physical impairment in 216 patients, and (2) by relating changes over time in the
      HAQ-S and the Functional Index with changes in patient reported pain and
      stiffness in 153 patients followed for at least 2 years. Sensitivity to change
      was measured from the responses of 155 patients who reported a qualitative change
      in the activity of their AS during followup. RESULTS: Most patients had mild
      functional disability, with median scores of 0.5 on the HAQ-S (possible range 0
      3), 0.375 on the HAQ (possible range 0-3), 11 on the Functional Index (possible
      range 0-40), and 5 on the AIMS2 (possible range 0-60). Scores on the HAQ-S (R2 =
      0.24) and the unmodified HAQ (R2 = 0.18) were more highly correlated with
      measures of physical impairment than were scores on the AIMS2 (R2 = 0.10) or the
      Functional Index (R2 = 0.09). Changes over time in the HAQ-S and HAQ were more
      closely related to changes in pain and stiffness than were changes in the
      Functional Index. The HAQ-S and HAQ were also more sensitive to change than the
      Functional Index. CONCLUSION: The HAQ-S showed greater construct validity and
      sensitivity to change than the Functional Index, but performed similarly to the
      unmodified HAQ.

PMID- 9918251
TI  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): a form
      of paraneoplastic polyarthritis?
AB  - OBJECTIVE: To describe the clinical and laboratory features and outcome of 6
      patients presenting with remitting seronegative symmetrical synovitis with
      pitting edema (RS3PE) revealing a solid tumor. METHODS: Patients with RS3PE who
      presented with a solid tumor and who had been seen between January 1, 1994, and
      December 31, 1996, were included in a retrospective multicenter analysis. These
      patients fulfilled McCarty's description of RS3PE and the following criteria: (1)
      bilateral pitting edema of both hands, (2) sudden onset of polyarthritis, (3) age
      >50 years, and (4) absence of rheumatoid factor (RF). RESULTS: Six male patients
      with RS3PE are described, of mean age 74 years (range 72-78), presenting
      prostatic (n = 4), gastric (n = 1), and colic (n = 1) adenocarcinomas. The clini
      cal picture was characterized by the classical form of RS3PE syndrome and by a
      deterioration in general condition, sometimes with fever. All patients were
      negative for RF and antinuclear antibodies. In 2 cases of prostatic
      adenocarcinoma serum levels of interleukin 6 (IL-6) were high, but decreased with
      treatment. In these 6 patients, the articular manifestations regressed totally or
      partially in response to corticosteroids, sometimes at low doses, associated in
      most cases with specific antitumoral therapy. None displayed erosion or distal
      bone destruction. The mean survival following discovery of RS3PE was 11 months
      (range 6-18), 5 patients dying of metastatic dissemination of their cancer and
      the 6th of myocardial infarction. CONCLUSION: RS3PE is a heterogeneous syndrome
      that can reveal a solid tumor, notably an adenocarcinoma. There exist no specific
      criteria to define its forms, but this syndrome should be kept in mind in the
      face of a deterioration in general health. Although the pathogenic mechanism is
      unknown, this could involve a type of paraneoplastic polyarthritis linked to the
      synthesis of a factor such as IL-6.

PMID- 9918253
TI  - Bowel permeability and CD45RO expression on circulating CD20+ B cells in patients
      with ankylosing spondylitis and their relatives.
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is reportedly associated with subclinical
      endoscopic gut inflammation in up to 57% of patients. Studies of bowel
      permeability, however, have not consistently revealed abnormalities in these
      patients. CD20+CD45RO+ expression is associated with increased antigen exposure,
      and previous work has shown increased expression in this B cell isoform in
      patients with Crohn's disease and their relatives, correlating with intestinal
      permeability abnormalities. We sought to re-examine intestinal permeability in
      patients with AS and their relatives, and relate any observed alterations in
      permeability with evidence of increased antigen presentation as assessed by the
      number of circulating B cells that were CD45RO positive. METHODS: We studied
      small intestinal and gastric permeability by measurement of excretion of
      lactulose, mannitol, and sucrose in 60 patients with AS and 24 of their first
      degree relatives. We also studied expression of CD20+CD45RO+ by flow cytometry in
      these patients. RESULTS: Both patients and first-degree relatives had
      significantly increased small intestinal, but not gastric, permeability compared
      to controls. Among patients, current users of nonsteroidal anti-inflammatory
      drugs (NSAID) had significantly increased small intestinal permeability compared
      to nonusers, but relatives not using NSAID also had increased permeability.
      CD20+CD45RO+ expression was increased in one-third of patients but did not
      correlate with permeability abnormalities. CONCLUSION: Patients with AS have
      altered small intestinal, but not gastric, permeability. NSAID use cannot explain
      all the abnormality. Bowel permeability abnormalities, possibly genetically
      determined, may antedate development of bowel or joint symptoms. Increased
      CD20+CD45RO+ expression suggests increased antigen exposure, which may be related
      to previous or current intestinal permeability abnormalities.

PMID- 9918254
TI  - Intradermal tophi in gout: a case-control study.
AB  - OBJECTIVE: To describe the characteristics of intradermal tophi in patients with
      gout and search for factors associated with their development. METHODS: This is a
      case-control study of patients with gout: cases (Group A, n = 21) had intradermal
      (not subcutaneous) plaques of monosodium urate (MSU) crystals located in sites
      distant to articular or paraarticular structures, and controls (Group B, n = 42)
      had gout but no intradermal tophi. Both Group A and Group B were paired by sex,
      age (+/-5 years), and duration of the disease (+/-3 years). Analysis included
      serum and urinary uric acid levels at first visit, radiographic stage of gout,
      the presence of associated diseases, and previous therapy, specifically, chronic
      glucocorticoid and diuretic usage. RESULTS: Intradermal tophi were located in the
      legs, forearms, buttocks, thighs, arms, and abdominal wall. Patients in Group A
      had a greater number of nonintradermal tophi in common sites (11.9+/-12.5 vs.
      4.2+/-7.9, mean +/- SD; p = 0.018), decreased glomerular filtration rate (46.74+/
      25.11 vs. 70.87+/-30.18 ml/min; p = 0.042), advanced radiographic changes (57.2
      vs. 7.1%; p = 0.0001), and longterm glucocorticoid self-medication (76 vs. 36%; p
      = 0.006). We found no differences in other associated diseases between groups.
      CONCLUSION: Intradermal tophi were commonly found in the legs and forearms, and
      less frequently in the buttocks, thighs, and abdominal wall of gouty patients,
      and were associated with longterm self-prescribed glucocorticoids and chronic
      renal failure. The occurrence of intradermal tophi in these patients appeared to
      correlate with advanced disease.

PMID- 9918255
TI  - Osteoarticular complications of brucellosis in an Atlantic area of Spain.
AB  - OBJECTIVE: To assess the frequency and clinical manifestations of osteoarticular
      brucellosis in an Atlantic area of Spain. METHODS: The case histories of all
      patients older than 14 years of age with active brucellosis diagnosed at the
      Hospital Xeral-Calde, Lugo, Spain, between October 1979 and October 1997 were
      reviewed. Diagnosis of brucellosis was by one of the following criteria:
      isolation of brucella species in blood or other fluids or tissue samples; or a
      clinical picture compatible with brucellosis in the presence of raised titers of
      specific antibodies by seroagglutination or Rose-Bengal plate agglutination
      tests. RESULTS: Forty-four patients (34 men, 10 women) of the 158 patients
      diagnosed with brucellosis (27.8%) had osteoarticular complications. Spondylitis
      (20/44; 45.5%) and sacroiliitis (15/44; 34.1%) were the most common
      complications. Patients with spondylitis were older and had a more chronic
      disease course than those with sacroiliitis or peripheral arthritis. Brucella
      abortus was the pathogenic strain responsible for human brucellosis in this
      region of Spain. CONCLUSION: In the Lugo region of Northwestern Spain
      osteoarticular brucellosis principally affects males and mainly involves spine
      and sacroiliac joints.

PMID- 9918256
TI  - Invasive Aspergillus spp infections in rheumatology patients.
AB  - OBJECTIVE: The number of immunocompromised patients in hospitals has increased,
      resulting in a concomitant increase in the number of Aspergillus spp infections,
      with an exceedingly high death rate. From January 1995 through June 1996, 7
      patients acquired invasive aspergillosis at a Maryland hospital (Hospital A). No
      cases had been detected in 1994. METHODS: To determine risk factors for
      infection, we conducted a case-control study and an environmental evaluation. A
      case was defined as histopathologic evidence of invasive Aspergillus spp
      infection in any Hospital A patient admitted from January 1994 through July 1996.
      RESULTS: Of 7 case patients identified, 5 were rheumatology patients hospitalized
      on 2 wards. Rheumatology case patients were more likely than randomly selected
      rheumatology patients without invasive Aspergillus spp infection (controls) to
      die (p = 0.004), to have longer hospitalization both in current (p = 0.008) and
      prior (p = 0.001) admissions, to receive high doses of intravenous
      immunosuppressive agents (p = 0.03), or to receive immunosuppressive agents for a
      longer period of time (p = 0.001). The environmental evaluation showed that
      construction areas were neither sealed off from patient care areas nor under
      negative pressure relative to patient-care areas. The air flow from patients'
      rooms was not positive in relation to the hallway and had only 1.6 air changes
      per hour. CONCLUSION: This investigation suggests that rheumatology patients,
      particularly those receiving high dose intravenous immunosuppressive agents, are
      at increased risk of invasive Aspergillus spp infection. A high index of
      suspicion for the diagnosis of nosocomial aspergillosis should be maintained in
      these patients and, when hospitalized, they should be assigned to rooms removed
      from or physically separated from construction activity.

PMID- 9918257
TI  - Fourteen cases of sarcomatous degeneration in Paget's disease.
AB  - OBJECTIVE: To describe characteristics of cases of sarcomatous degeneration in
      Paget's disease (SDP) recorded over 10 years in 2 French university hospitals,
      with particular emphasis on the pattern of this entity on magnetic resonance
      imaging (MRI). METHODS: Fourteen cases are described. Epidemiological, clinical,
      radiological, histological, and MRI features (in 3 cases) are compared to others
      in the literature. RESULTS: Nine men and 5 women (mean age 75.2+/-7.7 yrs) were
      studied. Paget's disease was monostotic in 5 cases and polyostotic in 9.
      Neurological complications were present in 10 cases. The mean interval between
      the first clinical signs and diagnosis was 4.4+/-4.7 months. The locations were:
      limbs 2, skull 2, pelvis 7, sacrum 3. The radiological pattern was lytic in 9
      cases, sclerotic in 3, and mixed in 2. MRI revealed a similar pattern in all 3
      cases studied (heterogeneous low signal intensity of the tumor on T1 weighted
      images increased after intravenous gadolinium administration and high signal
      intensity on T2 weighted images), whereas the radiological pattern was lytic in 2
      cases and sclerotic in one case. The diagnosis was proved by histological
      investigation in 11/14 patients (osteogenic sarcoma of different appearance in 7
      patients, fibroblastic sarcoma in one, fibrous histiocytoma-like sarcoma in one,
      and undifferentiated sarcoma in 2). Four patients had pulmonary metastases and 4
      patients are still alive with followup ranging from 5 months to 5 years.
      CONCLUSION: Paget sarcomas remain the most threatening sarcomas of bone, their
      prognosis being far more negative than primary sarcomas. Improvement in therapy
      strategies including surgery, radiation therapy, and chemotherapy might together
      provide better prognosis for SDP.

PMID- 9918259
TI  - Membrane-type-1 matrix metalloproteinase is abundantly expressed in fibroblasts
      and osteoclasts at the bone-implant interface of aseptically loosened joint
      arthroplasties in situ.
AB  - OBJECTIVE: To investigate the distribution pattern of membrane-type-1 matrix
      metalloproteinase (MT1-MMP) within the synovial-like interface membranes of
      failed prosthetic joints. METHODS: Interface tissue around loose arthroplasties
      containing both fibrous membrane and attached bone was obtained from 6 patients
      at revision surgery. In situ hybridization with digoxigenin labeled RNA probes
      was applied to investigate MT1-MMP expression in paraffin sections of the
      samples. In addition, double labeling using immunohistochemistry was performed to
      characterize MT1-MMP producing cells. RESULTS: Apart from being present in
      fibroblasts, MT1-MMP was also found expressed in osteoclasts at sites of bone
      resorption. Our results revealed no expression of MT1-MMP at parts of the
      membrane that originally had been located next to the prosthesis. In contrast,
      abundant staining for MT1-MMP was observed at sites attached to bone. MT1-MMP
      mRNA expression was more intense at those sites of bone resorption covered by a
      thicker interface membrane. CONCLUSION: These results indicate a role for MT1-MMP
      not only in matrix degradation by fibroblasts but also in osteoclast mediated
      bone resorption. Given the ability of MT1-MMP to activate MMP2 and MMP13, they
      suggest also that osteoclasts might contribute to matrix degradation by
      activating these MMP. This could be of potential interest not only for other
      conditions in which bone resorption by fibroproliferative tissue plays a role,
      but also to design novel strategies to prevent loosening of prosthetic joints.

PMID- 9918258
TI  - Influence of retinyl acetate on osteochondral junction chondrocytes in C3H and
      balb mice.
AB  - OBJECTIVE: To establish the pathophysiology of retinoid induced hyperostosis.
      METHODS: Radiographical, histological, ultrastructural, and immunohistochemical
      features of retinoid induced hyperostosis were evaluated using C3H-Heston mice
      and Balb mice. RESULTS: Dose dependent and progressive ossification was noted at
      extraosseous sites of both mouse strains. New bone formation was seen not only in
      the extraosseous tissues, but subchondral bone showed prominent proliferation.
      Major histopathological abnormalities appeared to take place in the chondrocytes
      near the osteochondral junctions, and some of the metaplastic chondrocytes near
      the osteochondral junction expressed osteocalcin and type I collagen,
      extracellular molecules normally present in bone. Species dependent
      responsiveness was also noted. CONCLUSION: Longterm administration of retinoids
      may induce an aberrant differentiation of the articular and entheseal
      chondrocytes near the osteochondral junctions, and the affected cells appeared to
      produce extracellular components including osteocalcin and type I collagen.

PMID- 9918260
TI  - Report of the National Institutes of Health Workshop on Kawasaki Disease.
AB  - The National Institute of Allergy and Infectious Disease, National Institutes of
      Health convened a workshop on Kawasaki disease, May 1997, co-chaired by Drs.
      Karyl Barron and Stanford Shulman. The goal of the workshop was to review the
      latest scientific advances relating to the epidemiology, etiology, pathogenesis,
      treatment, and complications of Kawasaki disease, along with future therapeutic
      options and proposed future research directions.

PMID- 9918261
TI  - Suspected hepatitis B vaccination related vasculitis.
AB  - Recombinant hepatitis B vaccination is widely used and severe side effects are
      rare. We describe 3 cases of vasculitis occurring after such immunization that
      are thought to have been vaccine induced. Vasculitides are now recognized as
      possible severe adverse side effects of immunization.

PMID- 9918262
TI  - Hypoglycemia induced by hydroxychloroquine in a type II diabetic treated for
      polyarthritis.
AB  - A 77-year-old man with type II diabetes taking a stable dose of subcutaneous,
      twice daily human insulin developed symmetrical, inflammatory, rheumatoid factor
      positive polyarthritis. Within 2 weeks of starting therapy with prednisone 5 mg
      daily and hydroxychloroquine 400 mg daily he had 2 episodes of severe
      hypoglycemic coma requiring emergency care. His blood glucose became controlled
      again when his insulin was decreased by 37%. There are no reported cases of
      hypoglycemia in diabetic or nondiabetic patients treated with hydroxychloroquine.
      Hydroxychloroquine has been reported to reduce insulin requirements in refractory
      type II diabetes by an average of 30%. When hydroxychloroquine is initiated for
      the treatment of polyarthritis in a type II diabetic requiring insulin or
      sulfonylurea treatment, blood glucose levels should be monitored closely and the
      insulin dose may need to be reduced.

PMID- 9918263
TI  - Severe rheumatoid arthritis.

PMID- 9918264
TI  - Report of the OMERACT task force on economic evaluation. Outcome Measures in
      Rheumatology.

PMID- 9918265
TI  - Patient based methods for assessing adverse events in clinical trials in
      rheumatology. Progress report for the OMERACT Drug Toxicity Working Party.
      Outcome Measures in Rheumatology.
AB  - There has been increasing recognition in recent years that the measurement of
      drug related toxicities in rheumatology clinical trials has been sub-optimal. The
      OMERACT Drug Toxicity Working Party was established to address this issue. The
      first task of the working party was to identify a minimum set of attributes of
      drug related toxicity that would be important to patients, clinicians,
      investigators, and policymakers. The working party then developed consensus on a
      standard set of properties for instruments to measure these attributes. Existing
      instruments in the field of rheumatology were ascertained by literature review
      and by contact with experts in the field. Four instruments were ascertained and
      evaluated using the guidelines developed by the working party. This report
      outlines the progress and preliminary results of these activities.

PMID- 9918266
TI  - The responsiveness of generic quality of life instruments in rheumatic diseases.
      A systematic review of randomized controlled trials.
AB  - To review the available evidence that has used generic instruments alone or in
      comparison with disease specific instruments. A systematic review was carried out
      using the methods recommended by the Cochrane Collaboration. We used MEDLINE and
      EMBASE searches and we performed a hand search of the abstracts listed under
      "quality of life" at American College of Rheumatology (ACR) meetings. Selection
      was limited to randomized controlled trials (RCT) using generic instruments in
      populations older than 18 years with any of the following diseases: rheumatoid
      arthritis, fibromyalgia, osteoporosis, osteoarthritis, systemic lupus
      erythematosus, and ankylosing spondylitis. Language was restricted to English
      papers. Studies using only disease-specific instruments were excluded. From 488
      articles retrieved, 13 reports of 10 randomized controlled trials were selected.
      There were 101 abstracts on quality of life in ACR abstract books; 78 abstracts
      contained data on generic instruments, and of these, 9 described their use in
      RCT. Despite a substantial increase in the number of papers and abstracts
      addressing different aspects of generic questionnaires, the majority of the
      papers were descriptive. The evidence is not yet available to document that any
      of the generic instruments pass the requirements of the OMERACT Filter.

PMID- 9918267
TI  - Sensitivity to change of generic quality of life instruments in patients with
      rheumatoid arthritis: preliminary findings in the generic health OMERACT study.
      OMERACT/ILAR Task Force on Generic Quality of Life. Life Outcome Measures in
      Rheumatology. International League of Associations for Rheumatology.
AB  - This is the initial report of the generic health OMERACT study concerned with the
      sensitivity to change of generic quality of life (QOL) measures. Our objective
      was to determine which QOL instrument is best able to show a statistically
      significant improvement in patients with rheumatoid arthritis (RA) demonstrating
      relevant improvement in a core set of disease activity and disease-specific
      disability measures. A multicenter controlled trial of a single group with
      repeated measurements at 0 (baseline), 3, and 6 months was conducted. All
      participating centers recruited 10 patients with RA who were about to start
      methotrexate therapy for the first time because of active disease. Assessments
      included disease activity measures, disease-specific disability measures, and
      generic QOL measures. To date, 40 patients have been recruited from 4 centers for
      the study. After 6 months of treatment many of the generic QOL measures showed a
      20% improvement from baseline and medium standardized response means around 0.5.
      In particular, the Nottingham Health Profile (NHP) and the Rheumatoid Arthritis
      Quality of Life (RAQOL) measures had the largest percentage improvement (22 and
      29%, respectively) and standardized response means (both with 0.54). Early
      results on the sensitivity of generic health QOL measures are promising, in
      particular for the NHP and RAQOL measures.

PMID- 9918268
TI  - Responsiveness of endpoints in osteoporosis clinical trials--an update.
AB  - As an update of our earlier paper, published as part of the Outcome Measures in
      Rheumatology Clinical Trials (OMERACT 3) proceedings in 1996, we surveyed the
      types of outcomes incorporated in recent clinical trials. A literature search was
      conducted on MEDLINE and Current Contents, from January 1996 to March 1998, using
      the search strategy recommended by the Cochrane Collaboration for the
      identification of randomized controlled trials (RCT). Two independent reviewers
      selected trials according to inclusion criteria. The same reviewers extracted
      data on clinical and radiographic fractures, pain, quality of life, and bone
      mineral density (BMD). Seventy-four RCT conducted on bone loss in postmenopausal
      women were identified. Most trials incorporated biochemical markers and BMD as
      outcome measures. Fewer trials included vertebral fractures, pain, height, and
      quality of life. The responsiveness is presented in terms of the sample size
      needed per group to show a statistically significant difference. The most
      responsive outcomes were pain, BMD, and biochemical markers. The number needed to
      treat to prevent one vertebral fracture ranged from 13 to 54, depending on the
      intervention and population. Investigators should examine the characteristics of
      the patient population and the nature of the intervention in determining the
      sample size required to demonstrate a significant effect. The selection of
      endpoints should be based on their responsiveness, feasibility, and the
      importance of using standardized outcomes. Standardized outcomes greatly
      facilitate the synthesis of available information into systematic reviews by
      groups such as the Cochrane Collaboration.

PMID- 9918269
TI  - Natural rubella infection with CD8+ T cell expansion and failure to detect viral
      genome in synovial fluid.

PMID- 9918270
TI  - Is labial salivary gland biopsy useful?

PMID- 9918271
TI  - Pulmonary capillary hemangiomatosis as cause of pulmonary hypertension in a young
      woman with systemic lupus erythematosus.

PMID- 9918272
TI  - First case of erythermalgia related to hepatitis B vaccination.

PMID- 9918273
TI  - Two cases of acute tubulointerstitial nephritis associated with panuveitis (TINU
      syndrome)

PMID- 9918274
TI  - Remission of psoriatic arthritis after porto-caval anastomosis in a patient with
      primary biliary cirrhosis.

PMID- 9918275
TI  - Spondylodiscitis due to Candida species.

PMID- 9918276
TI  - Effectiveness of topical calcitriol for localized scleroderma.

PMID- 9918277
TI  - Stroke--a medical emergency.
AB  - Stroke is the third leading cause of death and number one cause of disability in
      industrialised countries. A number of new therapeutic approaches are currently in
      development for use in the acute phase of ischaemic stroke and all trials have,
      to date, demonstrated the importance of early diagnosis and subsequent initiation
      of treatment. It is well known that, for most patients, there is a long delay
      between the onset of symptoms and the start of treatment. A number of factors are
      responsible for this time delay: signs and symptoms often go unrecognised by
      patients, relatives, and bystanders and, unlike trauma or myocardial infarction,
      stroke is not given a high priority by medical staff. Studies into the
      pathophysiology of acute ischaemic stroke have indicated that treatment options
      are likely to be optimised when early signs of stroke are recognised and
      treatment is initiated within six hours of symptom onset. Although a small number
      of stroke patients are treated as emergencies and attended to by the emergency
      medical services within this time window, this number could easily be increased
      by intensified public and emergency personnel education. In the future, it is
      hoped that treatments which must be administered within the first few hours of
      acute stroke will be able to be initiated by the emergency medical services. In
      the same way that hospitals are notified and prepared in advance to receive
      trauma victims, early notification by the emergency medical services about stroke
      patients would enable stroke teams to be present at admission, thus improving the
      likelihood of a better outcome for patients.

PMID- 9918278
TI  - Recent advances in the acute management of ischaemic stroke.

PMID- 9918279
TI  - Analysis of intensive care populations to select possible candidates for high
      dependency care.
AB  - OBJECTIVES: To identify the proportion, and range across intensive care units, of
      intensive care patients who might potentially be managed on a high dependency
      unit (HDU) using three different classification systems. METHODS: 8095 adult
      patients admitted to 15 intensive care units in the south of England between 1
      April 1993 and 31 December 1994 were studied. Patients were identified as
      potential HDU admissions if their APACHE III derived risk of hospital mortality
      was < or =10%, if they were categorised as a low risk monitor (LRM) patient using
      the Wagner risk stratification method, or if they did not require advanced
      respiratory support (ARS). RESULTS: 4146 patients (51.2%) had an APACHE III
      derived risk of hospital death of < or =10%, 1687 (20.8%) were classified as LRM,
      and 3860 (47.7%) did not receive ARS. The values for each intensive care unit
      ranged from 32.8-63.3% (APACHE III group), 7.2-29.9% (LRM group), and 14.4-68.2%
      (ARS group). No matter which of the three methods was used, there were
      significant differences between the 15 units (p<0.0001) with regard to the number
      of potential HDU patients identified within the scored population. CONCLUSIONS:
      The percentage of intensive care patients who might be more appropriately managed
      in a HDU varies considerably between hospitals, and depends upon both local
      circumstances and the method used to define a high dependency patient. However,
      whichever method is used, it appears that significant numbers of patients of low
      dependency status currently fill intensive care beds in the units studied. If
      these analyses are correct, the perceived national shortage in intensive care
      beds might be improved by the development of HDUs.

PMID- 9918280
TI  - Searching for the evidence in pre-hospital care: a review of randomised
      controlled trials. On behalf of the Ambulance Response Time Sub-Group of the
      National Ambulance Advisory Committee.
AB  - OBJECTIVES: To identify randomised controlled trials (RCTs) which evaluate
      aspects of pre-hospital care; to perform categorisation by theme; to compare the
      sensitivity and precision of the search databases. DATA SOURCES: August 1997
      updates of MEDLINE and EMBASE databases, using the Datastar online system. Papers
      published in 1987 or later were included, with no language restrictions. STUDY
      SELECTION: A trial was eligible for inclusion if it was judged, by two
      independent and blinded assessors, that participants followed up in the trial
      were definitely or possibly assigned prospectively to one of two or more
      alternative forms of healthcare with random allocation or a quasi-random method
      of allocation. RESULTS: The literature search retrieved 849 papers, of which 569
      (67%) were in MEDLINE and 486 (57%) in EMBASE. Forty one (5%) were confirmed as
      reports of RCTs or quasi-RCTs, and the total number of individual trials was 38.
      Ten of these trials dealt with thrombolytic drugs; 14 were concerned with other
      drugs, 12 with equipment, and two with other interventions. Four trials were
      based on a sample size of more than 1000, and seven reported a statistically
      significant effect on mortality. All 41 papers were in EMBASE, and all but one
      were also in MEDLINE. CONCLUSIONS: Evidence based policy making with respect to
      the organisation of pre-hospital services cannot depend on RCTs. In the current
      relative absence of such evidence, practitioners and decision makers must use
      alternative information sources. A future review could examine a broader range of
      literature and be based on a wider search of published and unpublished material.

PMID- 9918281
TI  - Prospective single blinded randomised controlled trial of two orally administered
      activated charcoal preparations.
AB  - OBJECTIVES: To compare two activated charcoal preparations (Carbomix and Actidose
      Aqua) in terms of amount ingested and incidence of vomiting after ingestion.
      METHODS: Single blinded prospective randomised controlled trial. RESULTS: The
      mean amount of charcoal ingested was Carbomix 26.5 g, Actidose-Aqua 19.5 g. The
      mean difference was 7 g (95% confidence interval (CI) 1.5 to 12.4 g). The
      incidence of vomiting was for the Carbomix 6% and the Actidose-Aqua 8%. The mean
      difference in vomiting was 2% (95% CI -0.8 to 4.8) CONCLUSIONS: Carbomix
      administration results in an increased amount of activated charcoal ingested
      after oral administration. Rates of vomiting after activated charcoal
      administration were low when compared with previously reported rates.

PMID- 9918282
TI  - The PEP transducer: a new way of measuring respiratory rate in the non-intubated
      patient.
AB  - OBJECTIVES: To explore the use of a pyroelectric polymer (PEP) film as a
      transducer for a simple respiratory rate monitor and to evaluate the transducer
      in a laboratory situation. METHODS: Laboratory evaluation of a new pyroelectric
      transducer for measurement of respiratory rate. RESULTS: The amplified output
      from the pyroelectric film produced an excellent respiratory trace when used on a
      normal spontaneously breathing subject. The transducer is cheap, robust, and
      reliable. CONCLUSIONS: PEP films have the potential to be used as cheap and
      effective transducers in respiratory rate monitors for non-intubated patients. In
      the laboratory, they have many desirable characteristics which should now be
      evaluated in a clinical setting.

PMID- 9918283
TI  - Excessive morphine requirements after pre-hospital nalbuphine analgesia.
AB  - Nalbuphine hydrochloride is an opioid agonist-antagonist that has gained
      acceptance as a pre-hospital analgesic agent. Nalbuphine has equal analgesic
      properties to morphine, has a low addiction potential, and can be stored and
      administered without restrictions, unlike morphine. To date no clinical evidence
      has been published to support the theoretical difficulty that the action of
      opioids administered after nalbuphine could be altered or negated. The following
      case reports highlight 10 patients who received nalbuphine pre-hospital and
      subsequently required higher doses of opioid analgesia than expected. The
      discussion summarises the properties of nalbuphine and identifies potential
      reasons why excessive amounts of opioid analgesia were required.

PMID- 9918284
TI  - Microbiological evaluation of infected wounds of the extremities in 214 adults.
AB  - OBJECTIVE: The aim of this multicentre prospective study was to analyse microbial
      pathogens cultured from an infected wound. METHODS: The study was performed in
      the emergency rooms of 10 public hospitals. All adult patients with a clinical
      diagnosis of cellulitis after a wound in the upper or lower extremities were
      included. Cultures were obtained with swabs from infected lesions. Micro
      organisms cultured were identified by the usual methods and susceptibility
      testing was performed. RESULTS: The study population consisted of 214 patients,
      153 men and 61 women, with a mean (SD) age of 40 (10) years. Wound cultures
      remained sterile in 28 cases and infected with micro-organisms in 186 cases. Of
      the 186 positive cultures, three were not identified. Of the 183 remaining
      cultures, one micro-organism was present in 132 patients (62%) and several micro
      organisms in 51 patients (24%). A total of 248 micro-organisms were isolated in
      183 patients. Staphylococcus and streptococcus were the most frequently isolated
      micro-organisms (56% and 21% respectively) followed by Gram negative bacilli
      (18%). Determination of the susceptibility to the antibiotics commonly used to
      treat wound infections showed resistance in some cases. CONCLUSION: These results
      support the need always to take culture specimens from infected wounds for
      microbiological evaluation and antibiotic susceptibility determination, so that
      adapted chemotherapy can be prescribed.

PMID- 9918285
TI  - UK accident and emergency departments and emergency contraception: what do they
      think and do?
AB  - OBJECTIVES: A postal questionnaire survey was conducted to assess what staff in
      UK accident and emergency (A&E) departments thought of providing an emergency
      contraception service, the degree of enthusiasm in and level of provision of the
      service, and staff attitudes to the introduction or continuation of provision of
      the service. METHODS: A questionnaire was sent to all 560 departments providing
      A&E services in the UK. RESULTS: Of the 560 units sent questionnaires, 355
      (63.4%) replied. Half the units were located in small county towns, and a quarter
      in large towns. Requests for emergency contraception were received by 96% of
      responding units, but only 57% provided treatment. Requests for emergency
      contraception in 84 of these units ranged between one and 50 per month. The A&E
      senior house officer (SHO) and the gynaecology SHO and registrar prescribed most
      of the pills. Nurses were more involved in nurse led or general practitioner (GP)
      led units. Initial treatment only was given by 77% of providing units while the
      remainder also discussed subsequent contraception. Follow up was arranged with
      GPs by 92 units, and with family planning clinics by 66 units. Information packs
      were available in only 37 providing units. A total of 155 of providing units felt
      it was worthwhile and 56% of respondents thought emergency contraception should
      be provided by A&E departments. However, 91 units could identify one or more
      groups within the hospital who were antagonistic to provision by A&E departments,
      of which non-A&E medical staff formed the largest group. Over the counter
      availability of emergency contraception was not supported by 62% of respondents.
      CONCLUSION: The results show that while the female population appears to see a
      need for emergency contraception services to be provided in A&E departments,
      there is some reluctance by UK A&E departments to provide the service. Given the
      current interest in approaches to reducing unplanned pregnancies, especially in
      teenagers, provision of emergency contraception by A&E departments requires a
      pragmatic approach to ensure their cooperation in providing the service when
      alternative sources of provision are not available.

PMID- 9918286
TI  - Attitudes towards general practice and primary care: a survey of senior house
      officers in accident and emergency.
AB  - OBJECTIVES: The attitudes and knowledge of hospital based staff about the
      capabilities of general practice may be important obstacles to continuity of care
      and the quality of communication at the primary-secondary care interface.
      However, little research has sought to investigate such factors or how they
      change over time. The study aims to assess how senior house officers (SHOs) in
      accident and emergency (A&E) departments perceive general practice, and to test
      how attitudes change during their six months' tenure. METHODS: Questionnaires
      were sent to all A&E SHOs working in the 27 A&E departments in South Thames
      region. At the end of the first month and at the end of the sixth months SHOs
      were asked to respond using 100 mm visual analogue scales to statements about the
      quality of general practitioner (GP) services in their area and their attitudes
      towards treating primary care patients in A&E. RESULTS: After sending reminders,
      135 (79%) SHOs responded to the questionnaire at the end of the first month, and
      115 (67%) responded to the questionnaire at the end of the sixth month; 104 (61%)
      responded to both. Statements relating to GP accessibility within and outside
      normal working hours, perceptions of patients' satisfaction with GP services,
      GPs' effectiveness in educating patients about use of services, and the
      frustrations and lack of reward of treating primary care patients scored most
      negatively. The overall trend was for attitudes to become more negative during
      SHOs' period of employment in A&E, particularly for those intent on hospital
      specialist careers or those working within London hospitals. CONCLUSIONS: The
      findings indicate the extent to which attitudes become more entrenched over time.
      This may lead to care that is more hospital focused. These issues need to be
      addressed if quality improvement is to occur across the A&E-primary care
      interface.

PMID- 9918287
TI  - Criminal injury compensation: from B to A.
AB  - Since its inception some 34 years ago the CICB has dealt with over 1000000
      applications and paid out over 1.6 bn pounds sterling to victims of violence. The
      recent changes to the scheme and the formation of the CICA have streamlined the
      process and resulted in a slight reduction in average payments, but with more
      consistency in the amounts paid. There is no indication that the steady increase
      of around 5% per annum in the numbers of applications will fall and the service
      will continue to be in great demand.

PMID- 9918288
TI  - Accident and emergency medicine--the next 25 years.

PMID- 9918289
TI  - Investigation and management of patients with pleuritic chest pain presenting to
      the accident and emergency department.
AB  - The assessment of a patient with pleuritic chest pain calls for a high degree of
      clinical acumen and a high degree of suspicion that the diagnosis might be
      pulmonary embolism. This area is one of the most difficult in A&E medicine (and
      indeed chest medicine). One error is to "think the best" when considering the
      diagnosis in such patients but experience soon teaches to "think PE" and diagnose
      less serious conditions only when pulmonary embolism has been excluded. A key
      consideration is the presence of risk factors. Because the diagnosis is
      difficult, there should be no hesitation in requesting a senior opinion or
      referring to the inpatient medical team. We have produced an algorithm (fig 1)
      for the investigation and management of pleuritic chest pain as discussed in this
      article. Three questions relating to this article are: (1) Can pulmonary embolism
      be the diagnosis in a patient with pleuritic chest pain but a normal chest
      radiograph, ECG, and arterial blood gases? (2) What is the chest radiograph
      abnormality which is most likely to alert you to the possibility of pulmonary
      embolism? (3) What percentage of patients with a low clinical suspicion of
      pulmonary embolism but a high probability V/Q scan will have pulmonary embolism
      demonstrated on pulmonary angiography? The three key references are The PIOPED
      Investigators, Dalen, and Fennerty.

PMID- 9918291
TI  - Comparison of primary coronary angioplasty and intravenous thrombolytic therapy
      for acute myocardial infarction.

PMID- 9918292
TI  - Does this patient have community-acquired pneumonia?

PMID- 9918293
TI  - Organising training for undergraduates and SHOs. Senior house officers.

PMID- 9918294
TI  - Mitral regurgitation presenting as localised right middle lobe pulmonary oedema.

PMID- 9918295
TI  - Traumatic pseudoaneurysm of the superficial temporal artery.

PMID- 9918296
TI  - Accident and emergency medicine or emergency medicine?

PMID- 9918297
TI  - Planning cannot rely on emergencies arriving by ambulance.

PMID- 9918298
TI  - Inappropriate ambulance usage is a retrospective diagnosis.

PMID- 9918299
TI  - On site computed tomography in the district general hospital for severe head
      injury.

PMID- 9918300
TI  - "Empirical" thrombolysis in catastrophic pulmonary embolism.

PMID- 9918301
TI  - Spontaneous carotid artery dissection.

PMID- 9918302
TI  - Minor injuries units.

PMID- 9918303
TI  - Risk of fire outweighed by need for oxygen and defibrillation.

PMID- 9918304
TI  - Child protection register--time for change.

PMID- 9918305
TI  - Relatives in the resuscitation room.

PMID- 9918306
TI  - Transfusion-transmitted diseases: risks, prevention and perspectives.
AB  - During the past decades major improvements in blood safety have been achieved,
      both in developed and developing countries. The introduction of donor counseling
      and screening for different pathogens has made blood a very safe product,
      especially in developed countries. However, even in these countries, there is
      still a residual risk for the transmission of several pathogens. For viruses such
      as the human immunodeficiency virus (HIV), and the hepatitis viruses B and C,
      this is due mainly to window-period donations. Furthermore, the threat of newly
      emerging pathogens which can affect blood safety is always present. For example,
      the implications of the agent causing new variant Creutzfeld-Jakob disease for
      transfusion practice are not yet clear. Finally, there are several pathogens,
      e.g. CMV and parvo B19, which are common in the general donor population, and
      might pose a serious threat in selected groups of immunosuppressed patients. In
      the future, further improvements in blood safety are expected from the
      introduction of polymerase chain reaction for testing and from the implementation
      of photochemical decontamination for cellular blood products. The situation in
      transfusion medicine in the developing world is much less favorable, due mainly
      to a higher incidence and prevalence of infectious diseases.

PMID- 9918307
TI  - Extensive apoptosis of bone marrow cells as evaluated by the in situ end
      labelling (ISEL) technique may be the basis for ineffective haematopoiesis in
      patients with myelodysplastic syndromes.
AB  - Apoptosis is a gene-directed cellular self-destruction which begins with
      internucleosomal cleavage of DNA and ends eventually with fragmentation of the
      nucleus. We have shown that the technique of ISEL of fragmented DNA appears to be
      an accurate and reliable measurement of the early stages of apoptosis. The
      present study was undertaken in order to define the incidence of programmed cell
      death in bone marrow (BM) haematopoietic and stromal cells of myelodysplastic
      syndromes (MDS). The ISEL technique was employed in 21 BM biopsies of MDS
      patients. The analysis showed that in 11/21 patients, >70% cells (high score)
      were undergoing programmed cell death while 5 patients showed up to 1/3 of the
      biopsy containing apoptotic cells and 2 patients had only few occasional ISEL
      positive cells. Stromal cells including fat cells, endothelial cells and
      fibroblasts were frequently in apoptosis in large clusters. Our results indicate
      that extensive apoptosis of haematopoietic cells documented in BM biopsies of MDS
      patients may be the explanation for the ineffective haematopoiesis which is the
      hallmark of these disorders.

PMID- 9918308
TI  - The effect of interferon alpha on myeloproliferation and vascular complications
      in polycythemia vera.
AB  - The effect of interferon alpha (IFN) on myeloproliferation and vascular
      complications was studied in 32 patients (17 female, 15 male; median age 60.5 yr)
      with polycythemia vera (PV). IFN therapy was initiated at a median time of 19
      months after diagnosis. Ten patients were pretreated with chemotherapy in
      addition to phlebotomy. IFN dose was 12 megaU/wk during the first year, 9
      megaU/wk during the second year and 12 megaU/wk thereafter. During IFN alpha
      treatment hematocrit level was 45.7% and remained at this level after the second
      year of treatment, compared to 46.5% before IFN. The frequency of phlebotomy
      before IFN was 0.49/month and dropped to 0.19/month (p <0.0005) during the first
      year of IFN treatment. IFN normalized high platelet and leukocyte counts in a
      majority of patients. The incidence of deep venous thromboses was 3.6%/yr before
      IFN alpha and 1.8%/yr during the first year of treatment. IFN-induced side
      effects were mainly flu-like symptoms, fever, fatigue and arthralgia. In
      conclusion, IFN allowed the reduction of the dose of chemotherapy and decreased
      the need of phlebotomy. Despite improvement of hematological parameters, it is
      still uncertain whether IFN alpha can improve clinical symptoms in PV.

PMID- 9918309
TI  - Quality assurance of CFU-GM assays: inter-laboratory variation despite standard
      reagents.
AB  - To investigate the hypothesis that commercial kits for CFU-GM (colony forming
      unit granulocyte-macrophage) assay will reduce the interlaboratory variation
      noted by many workers, we carried out a quality assurance exercise in 2 parts.
      There were 8 participants in the first study and each performed CFU-GM assays
      using their in-house method and a commercial kit (Stem Cell CFU Kit, Gibco) in
      parallel. In the second exercise there were 10 participants and each performed
      CFU-GM with in-house methods and with a different commercial medium (Methocult GF
      H4534, Stem Cell Technologies). Twelve samples of cryopreserved peripheral blood
      progenitor cells (PBPC) were analysed by each participant in each part of the
      study. A very wide range of results was found for the different in-house methods,
      but standardizing the clonogenic assay with the commercial kits did not reduce
      the variation seen. To improve the reproducibility of CFU-GM assays between
      laboratories, scrupulous attention should be paid to all the steps involved in
      the assays, as little progress will be made by using commercial medium in
      isolation from efforts to reduce other sources of variation.

PMID- 9918310
TI  - Haematopoietic response and bcl-2 expression in patients with acute myeloid
      leukaemia.
AB  - Bcl-2 expression, the number of apoptotic cells and the growth and
      differentiation of early bone marrow progenitor cells were studied in patients
      with confirmed diagnosis of acute myeloid leukaemia (AML). Bone marrow cells from
      normal individuals were used as controls. We observed an increased percentage of
      bcl-2-mononuclear bone marrow cells expression in AML patients in relation to
      controls (p =0.002). Accordingly, the number of apoptotic cells was reduced (p =
      0.001) and there was a negative correlation between bcl-2 expression and the
      number of apoptotic cells (r=-0.664, p<0.001). In addition, bcl-2 expression was
      significantly increased in the chemotherapy resistant group in relation to the
      responsive group (p = 0.03). Lower rate of survival was observed in the group of
      AML patients with autonomous proliferation (p=0.01). These results suggest that a
      high bcl-2 expression and the presence of autonomous proliferation are related to
      a poor prognosis in AML.

PMID- 9918311
TI  - The red cell mass, plasma erythropoietin and spleen size in apparent
      polycythaemia.
AB  - It has been shown previously that measurement of the spleen size and plasma
      erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work
      up of patients with polycythaemia vera. The aim of the present work was to
      evaluate their value in the assessment of apparent polycythaemia (AP). Therefore,
      over a 24-month period we routinely performed bone marrow biopsies, measurement
      of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma
      camera scintigraphy and determination of the plasma EPO concentration in
      consecutive patients referred to us because of elevated values for packed cell
      volume (>0.48 in females and >0.51 in males). After having excluded patients with
      clonal and secondary polycythaemias we were left with 38 patients (27 males and
      11 females) with AP. In all of them the measured RCM was within normal range,
      i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were
      characterized by moderate increase in RCM and a concomitant moderate decrease in
      PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in
      males and by 12% in females; conversely, as compared to the predicted values the
      average measured value for PV was reduced by 17% in males and by 8% in females.
      The average RCM for males was 29+/-3 ml/kg; the corresponding figure for females
      was 23+/-4 ml/kg. It was shown that 86% of the subjects had plasma EPO
      concentrations within the control range; the remaining had values slightly above
      or below the control range. The mean posterior spleen scan area was 57+/-16 cm2
      and mean left lateral area 57+/-17 cm2; the reference value for spleen scan area
      (for both projections) is 57+/-12 cm2. Of the patients 35/38 (92%) had a spleen
      scan area within the mean+2SD for controls and 38 subjects (100%) had values
      within the mean+3SD. It is concluded that measurement of plasma EPO and a careful
      assessment of the spleen size should always be considered in the evaluation of
      patients with elevated values for venous packed cell volume.

PMID- 9918312
TI  - 2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and
      hairy cell leukemia variant: 7-year experience in Poland.
AB  - Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell
      leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2
      chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily
      dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients
      treated with this type of regimen. Median follow-up amounted to 36 months. Fifty
      six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed
      after previous treatment. Splenectomy as a first-line therapy was performed in 23
      patients and 18 remaining patients received prednisone, chlorambucil or
      interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%)
      patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate
      of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72)
      did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in
      treatment of newly diagnosed patients and patients who relapsed after previous
      therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who
      achieved CR after 2-CdA and was usually manifested by very discrete changes in
      peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean
      progression-free survival (PFS) time in this group was 37.4 (range 10-66) months.
      Ten of 20 relapsed patients were retreated with 2-CdA given an identical course
      to the first one. Seven patients entered second CR lasting 19+ (range 8-47)
      months and 3 experienced PR. This confirms the previous observations that 2-CdA
      gives no resistance to leukemic clone. Ten remaining patients have not required
      retreatment so far and remain in a good clinical and hematological state. The
      results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and
      4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2
      with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were
      noted in 5 patients. 2-CdA-related side effects resulted mainly from
      myelosuppression and infectious complications. In conclusion we confirm the
      effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug
      is unable to completely eradicate the leukemic clone which results in the relapse
      of the disease. The real incidence of the relapse rate may be underestimated
      unless bone marrow biopsy is performed. The results of our study indicate that a
      2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion
      but more convenient to the patients, and may be given on an outpatient basis.

PMID- 9918313
TI  - Antibodies reactive with neutrophils following allogeneic haematopoietic stem
      cell transplantation.
AB  - Allogeneic haematopoietic stem cell transplants might induce immunological
      alterations leading to autoimmune-like syndromes. In particular neutrophil
      associated antigens could represent the target for autoantibodies against
      neutrophils in patients receiving an allogeneic peripheral stem cell or bone
      marrow transplantation, giving rise to granulocytopenia. With this aim we studied
      prospectively 43 allotransplanted patients for the presence of antibodies
      reacting with neutrophils (ARN), looking for a correlation with a post
      engraftment neutropenia. Our data showed that the direct test for ARN was
      positive in 30 patients. Interestingly, 7/7 patients who received a T-cell
      depleted marrow transplant developed ARN. Antibodies with a specific neutrophil
      antigen reactivity were detected in 4 patients, 1 with an anti-CD16/FcbetaRIIIb
      receptor reactivity and 3 with anti-NA 1 reacting patterns, respectively. From a
      clinical point of view, it was not possible to demonstrate a close and
      significant relationship between neutropenia and ARN, although patients showing
      ARN had slightly lower absolute levels of peripheral neutrophils until 6 months
      after BMT. In conclusion, ARN may be detected in the majority of patients
      following allogeneic stem cell transplantation; in addition, since ex vivo or in
      vivo T-cell-depletion leads to a higher percentage of patients positive for ARN,
      it could be hypothesized that "autoimmune-like" disorders in transplanted
      patients might be related to a T-cell derangement due to different numbers and
      subsets of T lymphocytes.

PMID- 9918314
TI  - A staging system for multiple myeloma based on the morphology of myeloma cells.
AB  - The morphology of myeloma cells is reported to be one of the prognostic factors
      in multiple myeloma (MM) patients. We analyzed the prognostic factors, including
      morphological classification, in 292 patients with MM in order to select poor
      risk patients who should be considered candidates for early intensive
      chemotherapy, including stem cell transplantation. Multivariate analysis was
      applied to 90 patients diagnosed between 1989 and 1996, because serum beta-2
      microglobulin (beta2M) has been measured regularly since 1989, and showed that
      serum albumin, serum beta2M, and the morphology of myeloma cells predicted
      survival. According to these factors, patients were divided into 3 risk groups; a
      high-risk group (14%), a intermediate-risk group (46%) and a low-risk group
      (40%). There were significant differences between survival times in these 3
      groups (median survival: high-risk, 16; intermediate-risk, 22; and low-risk, 44
      months).

PMID- 9918315
TI  - GVL and GVHD following the infusion of a limited number of donor CD3 cells in the
      therapy of leukaemia relapse after bone marrow transplantation.

PMID- 9918316
TI  - Detection of herpes simplex virus DNA in semen of men with genital HSV-2
      infection.
AB  - BACKGROUND AND OBJECTIVES: Previous studies, using viral culture, have suggested
      that herpes simplex virus (HSV) isolation from semen is rare. This study attempts
      to investigate further the role of semen in sexual transmission of HSV. GOALS OF
      THIS STUDY: To evaluate semen samples for HSV DNA with a sensitive polymerase
      chain reaction (PCR) test. STUDY DESIGN: Laboratory examination of 255 stored
      semen samples collected from 15 healthy men with genital HSV-2 infection during a
      prospective clinical trial. RESULTS: Herpes simplex virus DNA was detected in 8
      (3.1%) semen samples, 6 of which were collected during a herpes recurrence.
      Herpes simplex virus DNA was not detected in any of the 18 samples collected
      during acyclovir therapy. CONCLUSION: Herpes simplex DNA can be detected in
      semen, although it appears closely associated with clinical HSV reactivation.
      More detailed studies will be needed to assess the role HSV-2 in semen plays in
      transmission of infection.

PMID- 9918317
TI  - Determinants of reinfection with Chlamydia trachomatis.
AB  - BACKGROUND AND OBJECTIVES: Epidemiologic studies of chlamydial infections may
      often miss factors associated with the acquisition of infection. GOAL: To
      evaluate factors associated with risk for initial and recurrent Chlamydia
      trachomatis infections. STUDY DESIGN: A retrospective study of patients attending
      a sexually transmitted disease clinic and, within this retrospective cohort, a
      nested case-control study. RESULTS: Among initial-negative subjects the crude
      incidence rate was 11.5 per 1,000 months of follow-up. Among initial-positive
      subjects, the crude incidence rate was 28 per 1,000 months of follow-up (RR =
      1.8, 95% CI: 1.4-2.2). The increase in risk of infection associated with prior
      infection was independent of age. In the case-control study, a reduced risk of
      recurrent infection was associated with tubal ligation, hormonal contraception,
      and barrier contraception. CONCLUSIONS: As well as targeting sexually active
      adolescents, prevention programs should recommend repeat testing for all women
      with prior chlamydial infection, irrespective of age. Furthermore, issues related
      to personal control of health may modify risk for infection.

PMID- 9918318
TI  - Bayes' theorem-based assessment of VDRL syphilis screening miss rates.
AB  - BACKGROUND AND OBJECTIVES: Interlaboratory differences (and conflicting
      practices) in syphilis screening strategies (serial versus parallel test
      combinations) prompted us to determine an estimate of the diagnostic miss rate in
      the detection of (1) infected persons and (2) infected but untreated persons
      potentially affected by late active syphilis. GOAL: We set out to establish the
      most efficient syphilis screening strategy for two routine tests (VDRL and
      Treponema pallidum hemagglutination assay [TPHA]) with regard to our tested
      public health population (average VDRL+ TPHA+ and VDRL- TPHA+ reactor ages being
      59.9 years and 50.5 years, respectively. STUDY DESIGN: Retrospective analysis
      covered the results of a routine parallel VDRL and TPHA testing on 24,863 persons
      done in four public health laboratories. Nosologic sensitivity of the VDRL test
      (18.32%) was determined using the TPHA test as reference. The percentage of VDRL
      nonreactors among infected persons (TPHA reactors) was considered as the VDRL
      false negative rate (81.68%). We estimated the proportion of persons infected but
      untreated with potential late active syphilis using our own Bayes theorem-based
      procedure. RESULTS: The Bayes theorem-based estimate showed a significantly
      higher value for persons at risk of active late syphilis than the number of
      suspected cases obtained using the classical approach (25.1% versus 18.32%, or 83
      persons versus 61 of the 330 infected). CONCLUSION: In screening an older
      population, the VDRL test alone (or as the first of a series with TPHA as a
      confirmation test) may produce a diagnostic miss rate higher than the syphilis
      detection rate. Another miss in such a population is detected by the Bayes
      theorem-based method.

PMID- 9918319
TI  - Sexual experiences and condom use of heterosexual, low-income African American
      and Hispanic youth practicing relative monogamy, serial monogamy, and
      nonmonogamy.
AB  - BACKGROUND AND OBJECTIVES: To describe (a) demographic characteristics, (b)
      sexual history, (c) perceived HIV susceptibility, and (d) current sexual
      behavior, condom use, and alcohol and marijuana use of heterosexual, low-income
      African American and Hispanic youth categorized as relatively monogamous (n =
      577), serial monogamous (n = 171), or nonmonogamous (n = 278). STUDY DESIGN: Data
      were drawn from personal interviews with a probability sample of low-income
      youth, age 15 to 24 years, conducted in Detroit in 1991. RESULTS: Many group
      differences were found. For example, relatively monogamous youth were most likely
      to be female and Hispanic and to have engaged in unprotected intercourse. Serial
      monogamous youth were younger and most likely to have used condoms at last
      intercourse. Nonmonogamous youth initiated intercourse earlier and were most
      likely to have experienced oral and anal intercourse and to have used alcohol and
      marijuana. CONCLUSION: Risk reduction programs may need to be tailored
      differently to accommodate the needs of these three distinct subgroups of youth.

PMID- 9918320
TI  - Subsequent sexually transmitted infections among adolescent women with genital
      infection due to Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas
      vaginalis.
AB  - OBJECTIVE: To identify factors associated with subsequent sexually transmitted
      infection (STI) (within 1 year of initial infection) due to Chlamydia
      trachomatis, Neisseria gonorrhoeae or Trichomonas vaginalis. DESIGN: Prospective
      cohort study. SETTING: A sexually transmitted diseases clinic and four community
      based primary care clinics for adolescents. PARTICIPANTS: Female patients (ages
      15 to 19 years) with initial diagnosis of chlamydia, gonorrhea, or trichomonas.
      MAIN OUTCOME MEASURES: Subsequent infection by chlamydia, gonorrhea, or
      trichomonas. RESULTS: More than 40% of subjects were subsequently infected by at
      least one STI. Reinfection was common, but infections with sexually transmitted
      organisms other than the initial infecting organism were also common. Predictors
      of subsequent infection were black race, gonorrhea as the initial infection, two
      or more sex partners in the previous 3 months, and inconsistent condom use.
      CONCLUSIONS: Subsequent STI frequently follow an initial STI, but there is
      substantial variation in the causal organism. These data suggest the importance
      of comprehensive STI prevention programs for adolescents rather than organism
      specific interventions.

PMID- 9918321
TI  - Reliability of self-reported sexual histories: test-retest and interpartner
      comparison in a sexually transmitted diseases clinic.
AB  - BACKGROUND AND OBJECTIVES: The objective was to assess reliability of self
      reported sexual histories among sexually transmitted disease clinic attendees who
      enrolled in a study in 1994. GOAL OF THIS STUDY: Knowledge about the reliability
      of sexual data is important to decide whether these measures of sexual behavior
      can be used in epidemiologic studies of sexually transmitted diseases. STUDY
      DESIGN: In 288 attendees, degree of agreement was assessed in responses to an
      identical set of sexual questions asked independently by a medical doctor and a
      public health nurse and in responses made by members of the same couple (n = 50)
      to a public health nurse. RESULTS: In the test-retest comparison, high agreement
      was found for most questions: kappa-values and exact agreement ranged from 0.73
      to 0.96 and 54% to 99%, respectively. Participants interviewed by the medical
      doctor reported significantly lower numbers of partners and a higher age at first
      intercourse. Stratified analyses showed variability in agreement across
      subgroups. Most consistent, women provided more reliable reports than men. In the
      comparison of couples, substantial agreement was found for the municipality where
      they met (88% agreement; kappa = 0.72) and contraceptive method (87% agreement;
      kappa = 0.60), but only moderate agreement was found for frequency of sexual
      intercourse (26% agreement; kappa = 0.50). CONCLUSION: The authors conclude that
      data on sexual behavior can be collected reliably among sexually transmitted
      disease clinic attendees, although reporting bias does occur. The frequency of
      sexual intercourse was not sufficiently reliable and should be interpreted as an
      estimate only.

PMID- 9918322
TI  - Epidemiologic aspects of male gonococcal infection in Greece.
AB  - OBJECTIVE: To report male gonorrhea incidence trends between the years 1974 and
      1996 and compare the epidemiologic characteristics of the affected population
      during periods of high and low incidence of the disease. STUDY DESIGN:
      Retrospective study of all available data for male gonorrhea cases recorded
      annually in a major STD hospital in Greece since 1974. RESULTS: An abrupt drop in
      gonorrhea relative incidence occurred in 1986, followed by low rates thereafter.
      In the context of the overall decline in the incidence of the disease, a shift to
      older ages, longer time elapsed before seeking medical assistance, and higher
      proportion of disease repeaters was noticed among the patients. Infections caused
      by penicillinase-producing gonococci were strongly associated with contacts
      outside the country or with foreigners and their incidence presented erratic time
      fluctuations, indicating that they have not been established as endemic in the
      Greek population. CONCLUSION: The core group hypothesis in terms of nighttime
      sociosexual activity can be used to interpret most of the findings.

PMID- 9918323
TI  - Establishing efficient partner notification periods for patients with chlamydia.
AB  - OBJECTIVES: To delineate chlamydia partner notification periods with high
      proportions of infected, untreated sexual partners, and to evaluate relevant
      Centers for Disease Control (CDC) recommendations. METHODS: Disease Intervention
      Specialists (DIS) offered contact tracing services to all chlamydia patients (N =
      1,309) reported in Colorado Springs between July 1996 and June 1997. Patients
      were asked to identify sexual partners during the 180 days preceding treatment.
      Partners were actively sought by DIS and offered DNA amplification testing.
      RESULTS: Of 1,309 patients, 1,109 were interviewed, resulting in 2,293 named
      partners. Two fifths of eligible partners were located; inability to examine
      partners was related to time of last exposure and to frequency of sexual
      exposure. Of located partners, 95% were tested with DNA amplification technology.
      Adherence to CDC criteria identified 88% of infected, untreated partners; the
      other 12% consisted mainly of epidemiologically important asymptomatic men whose
      infection is seldom identified by current public health interventions.
      CONCLUSIONS: The chlamydia partner notification recommendations of the CDC are
      adequate, but miss men with long-standing infection. These men contribute to
      entrenched chlamydia endemicity; targeted programs to screen high-risk men merit
      serious consideration.

PMID- 9918324
TI  - The etiology of genital ulcer disease by multiplex polymerase chain reaction and
      relationship to HIV infection among patients attending sexually transmitted
      disease clinics in Pune, India.
AB  - OBJECTIVES: To determine the etiology of genital ulcer disease (GUD) among
      patients attending sexually transmitted disease (STD) clinics in Pune, India, and
      to examine the relationship to HIV infection and compare the clinical diagnosis
      of GUD with the results of a multiplex polymerase chain reaction (M-PCR) assay
      for Treponema pallidum, herpes simplex virus (HSV), and Hemophilus ducreyi
      infection. METHODS: Between June 20, 1994, and September 26, 1994, 302 patients
      with a genital ulcer were evaluated. Clinical etiology of GUD was based on
      physical appearance and microbiologic evaluations which included darkfield
      microscopy and serology for syphilis. Swabs of each genital ulcer were tested for
      HSV antigen by enzyme immunoassay (Herpchek; Dupont, Wilmington, DE) and
      processed in a multiplex PCR assay (M-PCR; Roche, Branchburg, NJ) for
      simultaneous detection of HSV, Treponema pallidum, and Hemophilus ducreyi.
      RESULTS: Two hundred seventy-seven men and 25 women with a median age of 25 were
      evaluated. The seroprevalence of HIV was 22.2%. The etiology of GUD as determined
      by M-PCR was HSV (26%), H. ducreyi (23%), T. pallidum (10%), and multiple
      infections (7%); no etiology was identified in 34%. HIV seroprevalence was higher
      among those patients positive for HSV compared with other etiologies (OR = 2.1,
      CI: 1.2-3.7; p = 0.01). When compared with M-PCR, the Herpchek test was 68.5%
      sensitive and 99.5% specific. Darkfield detection for T. pallidum was 39%
      sensitive and 82% specific, in contrast to rapid plasma reagin and fluorescent
      treponemal antibody absorption test, which was 66% sensitive and 90% specific.
      Clinical diagnosis alone or in combination with basic laboratory tests showed
      poor agreement with M-PCR.

PMID- 9918325
TI  - Etiology of genital ulcer disease and its relationship to HIV infection.

PMID- 9918326
TI  - Isolation and short term culture of canine adrenal microvascular endothelial
      cells.
AB  - A rapid method for the isolation of endothelial cells from canine adrenal glands
      is described. The technique is based on collagenase digestion of adrenal glands
      following mechanical tissue disruption. The endothelial cells attach and spread
      onto plastic petri dishes coated with a commercial attachment factor
      approximately one hour after seeding. Duration to first passage was approximately
      one week. Doubling times were 2-3 days. Cells were positively identified with
      immunoperoxidase staining for von Willebrand factor antigen.

PMID- 9918327
TI  - Mast cells of the bovine trachea: staining characteristics, dispersion techniques
      and response to secretagogues.
AB  - Sections of the lower trachea of cattle, fixed in either Carnoy's or formalin,
      were stained with toluidine blue, alcian blue, or alcian blue and safranin O to
      study the mast cell population. After toluidine blue staining, about twice as
      many cells in tissue fixed in Carnoy's contained dark blue granules compared with
      tissue fixed in formalin. In addition, for the first time in cattle, a population
      of cells containing red granules was identified after staining with alcian blue
      and safranin O. Most of these red granules were formalin sensitive. An enzymatic
      dispersal technique for mast cells is described that yielded 9.4+/-0.4% mast
      cells (percentage of nucleated cells) with a viability of 92.3+/-0.6%.
      Spontaneous histamine release was 3.3+/-0.8%. Dispersed mast cells were
      challenged with various immunological and nonimmunological secretagogues. The
      calcium ionophores, A23187, ionomyocin, and BrX537A, were effective in releasing
      up to 94% of histamine in mast cells in a dose-response relationship. Pasteurella
      haemolytica culture supernate caused about 10% histamine release at a dose of 0.5
      mg/mL after correction for spontaneous release. The average histamine content of
      the mast cells was 6.6+/-1.0 pg/cell. Cytospins of dispersed cells fixed in
      Carnoy's and stained with alcian blue and safranin O contained mast cells with
      blue and red granules, and a few cells with a mixture of both granule types.
      Based on the effects of type of fixation, staining characteristics and histamine
      content, a mix of subtypes of mast cells is present in the bovine trachea.
      However, functionally they respond to secretagogues differently than rodent mast
      cells. Without an immunological secretagogue, studies to determine compounds that
      will be effective in blocking mast cell degranulation will be limited.

PMID- 9918328
TI  - Dependence of superoxide anion production on extracellular and intracellular
      calcium ions and protein kinase C in PMA-stimulated bovine neutrophils.
AB  - The involvement of both intracellular and extracellular calcium, as well as the
      activation of protein kinase C (PKC), in phorbol myristate acetate (PMA)
      stimulated respiratory burst in bovine neutrophils has been studied. PMA
      significantly stimulated the superoxide anion production by these cells. The
      increased production of superoxide anion was inhibited by BAPTA/AM, an
      intracellular calcium ([Ca2+]i) chelator, but not affected by EGTA, an
      extracellular calcium ([Ca2+]0) chelator. PMA also induced PKC activation, and a
      PKC inhibitor, calphostin C, blocked the stimulatory effect of PMA on superoxide
      anion production by the neutrophils. Therefore, we conclude that PMA-induced
      respiratory burst in bovine neutrophils is [Ca2+]i- but not [Ca2+]0-dependent,
      and also requires PKC activation.

PMID- 9918329
TI  - The effects of prednisone and azathioprine on circulating immunoglobulin levels
      and lymphocyte subpopulations in normal dogs.
AB  - This study investigates serum immunoglobulin (SIg) levels and lymphocyte
      subpopulations in normal dogs in response to putative immunosuppressive doses of
      prednisone and/or azathioprine. The objectives were to quantify SIg levels and
      lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal
      dogs both before and after the administration of prednisone and/or azathioprine
      at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each.
      Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete
      blood count (CBC)and flow cytometry were collected prior to the administration of
      any drugs and again after 14 d of azathioprine, prednisone or azathioprine and
      prednisone. Peripheral blood mononuclear cells were isolated using density
      centrifugation and were incubated with monoclonal antibodies reacting with CD4+,
      CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified
      using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg
      levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P <
      0.05) decreases in all SIg levels, all lymphocyte subpopulations and erythrocyte
      numbers, and had an increase in neutrophil counts. Prednisone and azathioprine
      treated dogs had significant (P < 0.05) decreases in serum IgG levels and Thy-1+
      and CD8+ lymphocyte subpopulations, with an increase in the CD4:CD8. These dogs
      also had a significant decrease in erythrocyte number and a significant increase
      in the monocyte count. These findings suggest that azathioprine and prednisone in
      combination or prednisone alone may be useful for the treatment of T cell
      mediated diseases since decreased circulating T cell levels were demonstrated
      following treatment. The combination of drugs or azathioprine alone may not be
      appropriate for treatment of acute or autoantibody-mediated immune disease,
      because SIg levels were minimally affected by treatment.

PMID- 9918330
TI  - Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and
      intramuscular administration to sheep.
AB  - The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6
      sheep, after intravenous and intramuscular injection at a single dose rate of 20
      mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium
      sulbactam). The drugs were distributed according to an open 2-compartment model
      after intravenous administration and a one-compartment model with first order
      absorption after intramuscular administration. The apparent volumes of
      distribution calculated by the area method of ampicillin and sulbactam were
      0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances
      were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half
      lives of ampicillin after intravenous and intramuscular administration were
      0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half
      lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability
      after intramuscular injection was high and similar in both drugs (72.76+/-9.65%
      for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma
      concentrations of ampicillin and sulbactam were reached at similar times (0.25+/
      0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar
      but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L
      of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar
      pharmacokinetic behavior after intramuscular administration in sheep. Since the
      plasma concentrations of sulbactam where consistently higher during the
      elimination phase of their disposition, consideration could be given to
      formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio.

PMID- 9918331
TI  - Romifidine, medetomidine or xylazine before propofol-halothane-N2O anesthesia in
      dogs.
AB  - The objective of this paper was to evaluate romifidine as a premedicant in dogs
      prior to propofol-halothane-N2O anesthesia, and to compare it with the other
      alpha2-agonists (medetomidine and xylazine). For this, ten healthy dogs were
      anesthetized. Each dog received 3 preanesthetic protocols: atropine (10 microg/kg
      BW, IM), and as a sedative, romifidine (ROM; 40 microg/kg BW, IM), xylazine (XYL;
      1 microg/kg, IM), or medetomidine (MED; 20 microg/kg BW, IM). Induction of
      anesthesia was delivered with propofol 15 min later and maintained with halothane
      and N2O for one hour in all cases. The following variables were registered before
      preanesthesia, 10 min after the administration of preanesthesia, and at 5-minute
      intervals during maintenance: PR, RR, rectal temperature (RT), MAP, SAP, and DAP.
      During maintenance, arterial oxygen saturation (SpO2), end-tidal CO2 (EtCO2) and
      percentage of halothane necessary for maintaining anesthesia (%HAL) were also
      recorded. Induction dose of propofol (DOSE), time to extubation (TE), time to
      sternal recumbency (TSR) and time to standing (TS) were also registered. The
      statistical analysis was carried out during the anesthetic period. ANOVA for
      repeat measures revealed no differences between the 3 groups for PR and RR;
      however, MAP, SAP and DAP were higher in the MED group; SpO2 was lower in MED and
      EtCO2 was lower in ROM; %HAL was higher in XYL. No statistical differences were
      observed in DOSE, TE, TSR or TS. Percentage of halothane was lower in romifidine
      and medetomidine than in xylazine premedicated dogs also anesthetized with
      propofol. All the cardiorespiratory variables measured were within normal limits.
      The studied combination of romifidine, atropine, propofol, halothane and N2O
      appears to be a safe and effective drug combination for inducing and maintaining
      general anesthesia in healthy dogs.

PMID- 9918332
TI  - Metoclopramide ameliorates the effects of endotoxin on gastric emptying of
      acetaminophen in horses.
AB  - The effect of metoclopramide on gastric emptying of a liquid marker in horses was
      evaluated by measuring serum concentrations of acetaminophen. Gastric emptying
      was determined in normal, fasted horses (n = 7), horses given endotoxin
      intravenously (n = 7), and horses given intravenous metoclopramide plus endotoxin
      (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax),
      the maximum serum concentration (Cmax), and the area under the serum
      acetaminophen concentration vs time curve (AUC) were compared among treatment
      groups. Endotoxin caused a profound delay in gastric emptying, and pretreatment
      with metoclopramide significantly (P < 0.05) ameliorated this effect.

PMID- 9918333
TI  - Synergistic effects of bovine respiratory syncytial virus and non-cytopathic
      bovine viral diarrhea virus infection on selected bovine alveolar macrophage
      functions.
AB  - The effect of bovine respiratory syncytial virus (BRSV) and non-cytopathic bovine
      viral diarrhea virus (ncpBVDV) infection on selected bovine alveolar macrophage
      (AM) functions was investigated. Alveolar macrophages were harvested from 2- to 6
      month-old calves seronegative for BRSV and BVDV and inoculated with approximately
      1 median cell culture infective dose of virus per AM. Control, BRSV infected,
      ncpBVDV-infected and BRSV-ncpBVDV coinfected AM cultures were evaluated for Fc
      receptor expression, phagosome-lysosome fusion, superoxide anion (O2-)
      production, and chemotactic activity on Days 1, 3, 5, and 7 post-infection. Both
      single and combined viral infections significantly depressed AM Fc receptor
      expression, phagosome-lysosome fusion, and secretion of chemotactic factors with
      a more significant synergistic depression seen in BRSV-ncpBVDV coinfection.
      Production of O2- by AM was not decreased by either BRSV or ncpBVDV infection,
      but was significantly decreased by coinfection with BRSV-ncpBVDV. The present
      study confirms previous reports of BRSV effects on AM functions and indicate that
      ncpBVDV affects AM functions in vitro. Coinfection with BRSV-ncpBVDV produced a
      synergistic depression on AM functions.

PMID- 9918334
TI  - Formation of virus-like particles when the polyprotein gene (segment A) of
      infectious bursal disease virus is expressed in insect cells.
AB  - The baculovirus expression vector system was used to examine the expression of
      the full-length infectious bursal disease virus (IBDV) segment A cDNA, which
      encodes the structural proteins in a polyprotein precursor that is
      autocatalytically cleaved to VPX, VP3, and VP4. No VP2 was observed in lysates of
      recombinant baculovirus infected cells indicating the lack of processing of VPX
      to VP2 in this system. Virus-like particles (VLP) were purified from the infected
      insect cells, and on negative staining electron microscopy, looked very similar
      to authentic IBDV particles in shape and size, suggesting that processing of VPX
      to VP2 is not necessary for capsid assembly.

PMID- 9918335
TI  - Intracellular fate of Mycobacterium avium subspecies paratuberculosis in
      monocytes from normal and infected, interferon-responsive cows as determined by a
      radiometric method.
AB  - The ability of Mycobacterium avium subsp. paratuberculosis to survive in bovine
      monocytes was studied using radiometric (BACTEC) culture, standard plate counting
      and microscopic counting of acid-fast stained monocyte monolayers. Results of
      microscopic counts sharply contrasted with results of viable counts determined
      both by plate counting and radiometric counting. We observed an early phase (the
      first 6 d after in vitro infection) of intracellular bacillary growth, followed
      by a later phase of mycobacteriostasis or killing (up to 12 d after in vitro
      infection) in monocytes from non-infected cows. The data suggest that
      multiplication and death of M. avium subsp. paratuberculosis occur simultaneously
      in bovine monocytes infected in vitro. Using the BACTEC method, we compared the
      ability of bovine monocytes from normal cows and cows infected with M. avium
      subsp. paratuberculosis and showing evidence of a strong Thl-like cellular immune
      response to ingest and inhibit the intracellular growth of M. avium subsp.
      paratuberculosis. There was a trend toward greater phagocytosis and faster
      killing of Mycobacterium avium subsp. paratuberculosis by monocytes from the
      infected, immune responder cows. However, the observed numbers of viable M. avium
      subsp. paratuberculosis at each time after monocyte infection were not
      significantly different between normal and infected cows.

PMID- 9918336
TI  - Production and characterization of monoclonal antibodies specific for Leptospira
      borgpetersenii serovar hardjo type hardjobovis and Leptospira interrogans serovar
      hardjo type hardjoprajitno.
AB  - Murine monoclonal antibodies were produced by immunizing BALB/c mice with a
      killed whole-cell antigen prepared from Leptospira borgpetersenii serovar hardjo
      type hardjobovis. Six of these antibodies recognized epitopes on the homologous
      antigen and on whole-cell antigen prepared from Leptospira interrogans serovar
      hardjo type hardjoprajitno. These antibodies did not cross-react with whole-cell
      antigens prepared from L. borgpetersenii serovar sejroe, 10 other pathogenic
      Leptospira serovars, or the saprophytic Leptospira biflexa serovar patoc. Three
      other monoclonal antibodies reacted with antigens prepared from the 2 hardjo
      serovars and serovar sejroe but not with antigens from the 10 other pathogenic
      serovars, or serovar patoc. The epitopes recognized by all of the hardjo-specific
      antibodies and 2 of the 3 hardjo/sejroe-specific antibodies were susceptible to
      sodium meta-periodate oxidation. All of the antibodies were characterized by
      Western blots with the hardjobovis whole-cell antigen. Each of the 9 monoclonal
      antibodies was inhibited from binding to the hardjobovis antigen by bovine sera
      which were obtained from cattle experimentally infected with hardjobovis and from
      field cattle, with anti-serovar hardjo microscopic agglutination test antibody
      titres ranging from 100 to 12800. Some of these antibodies may be suitable for
      incorporation into competitive enzyme immunoassays for the specific detection of
      antibodies to either of the hardjo serovars.

PMID- 9918338
TI  - Alpha-synuclein and Parkinson's disease.

PMID- 9918337
TI  - Pathogenesis of porcine Actinobacillus pleuropneumonia, part II: roles of
      proinflammatory cytokines.
AB  - The in vitro production of proinflammatory cytokines after stimulation with
      Actinobacillus pleuropneumoniae and the relation of these cytokines in vivo with
      the disease caused by A. pleuropneumoniae were investigated. Within 24 h, in
      vitro stimulation by A. pleuropneumoniae (serotype 1) preparations, including
      killed bacteria, bacterial culture supernatant, lipopolysaccharide, and bacterial
      extracts, porcine pulmonary alveolar macrophages (PAM) produced significant (P <
      0.05) amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1)
      as measured by bioassays. The supernatants containing interleukin-8 from PAM
      after stimulation by bacterial preparations showed significant neutrophil
      chemotaxis, while bacterial preparations alone did not. After in vivo infection
      with A. pleuropneumoniae, the mean levels of TNF-alpha and IL-1 in serum, as
      measured by bioassays, were elevated 37- to 27836-fold for TNF-alpha and 11- to
      5941-fold higher for IL-1 within 4 d post-infection, depending on the treatments,
      and remained elevated up to Day 7. Both cytokines were also detected in porcine
      lungs by bioassays and immunocytochemistry. The results indicated that both
      secreted and surface components of A. pleuropneumoniae can stimulate PAM to
      produce proinflammatory mediators. Neutrophil chemoattractants rather than
      bacterial components are the major factor causing acute lung inflammation. The
      elevation of TNF-alpha and IL-1 in pigs occurred coincident with the onset of
      acute clinical disease.

PMID- 9918339
TI  - A data-driven approach to the study of heterogeneity in idiopathic Parkinson's
      disease: identification of three distinct subtypes.
AB  - Idiopathic Parkinson's disease (IPD) has been subclassified on the basis of
      predominant motor symptomatology, age at disease onset, depressive affect, and
      cognitive performance. However, subgroups are usually arbitrarily defined and not
      reliably based on qualitatively distinct neuropathology. We explored
      heterogeneity in IPD in a data-driven manner using comprehensive demographic,
      motor, mood, and cognitive information collected from 176 patients with IPD.
      Cluster analysis revealed three subgroups of patients at a disease duration of
      5.6 years and two subgroups at 13.4 years. The subgroups may represent the
      clinical progression of three distinct subtypes of IPD. The "motor only" subtype
      was characterized by motor symptom progression in the absence of intellectual
      impairment. Equivalent motor symptom progression was shown by the "motor and
      cognitive" subtype which was accompanied by executive function deficits
      progressing to global cognitive impairment. The "rapid progression" subtype was
      characterized by an older age at disease onset and rapidly progressive motor and
      cognitive disability. There was no relationship between the motor and cognitive
      symptoms in any subtype of IPD. We conclude that the clinical heterogeneity of
      IPD is governed by distinct neuropathologic processes with independent etiologic
      influences.

PMID- 9918341
TI  - Nutritional and occupational factors influencing the risk of Parkinson's disease:
      a case-control study in southeastern Sweden.
AB  - PURPOSE AND METHODS: To investigate the possible impact of nutritional and
      environmental risk factors for idiopathic Parkinson's disease (IP), a case
      control study was performed in the county of Ostergotland in southeastern Sweden.
      The study involved 113 cases of IP and 263 control subjects. Dietary, drinking,
      and smoking habits, as well as previous occupation, were requested in a
      structured questionnaire. RESULTS: No increased risk was found for any of the
      nutritional items in which information was requested. A reduced risk was found
      for coffee, wine, and liquor at various consumption levels but also for fried or
      broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes.
      All these food and drink items contain niacin. As in many studies, the frequency
      of preceding and present smoking was reduced in IP patients. Various occupational
      groups and exposures were analyzed and increased risks of IP in men were found
      for agricultural work along with pesticide exposure; this was also the case for
      male carpenters and female cleaners. CONCLUSIONS: The findings indicate that
      nutritional factors and occupational exposures, especially to pesticides, could
      be of etiologic importance in IP.

PMID- 9918340
TI  - Dietary factors in Parkinson's disease: the role of food groups and specific
      foods.
AB  - PURPOSE: The association between self-reported past food intake and Parkinson's
      disease (PD) was investigated in a case-control study of men and women aged 40-89
      years. METHODS: Newly diagnosed idiopathic PD cases were ascertained from
      neurologists, and from outpatient and pharmacy computerized databases, at the
      Group Health Cooperative (GHC) clinics in the Puget Sound region of Washington
      state. Control subjects were chosen from the GHC patient roster and had no
      reported history of diagnosed neurodegenerative disease. Dietary data were
      obtained from structured questionnaires. RESULTS: An increase in PD risk with
      increasing intake was noted for foods that contain animal fat and foods
      containing vitamin D. Intake of fruits, vegetables, meats, bread and cereals, or
      foods containing vitamins A, C, E, or iron was not significantly related to PD
      risk. Vitamin use, in general, was also not found to be related to PD risk,
      although a significant trend of increasing risk of PD was noted for intake of
      vitamin A supplements. CONCLUSIONS: Although these data support previous findings
      of no association of past intake with most food groups and PD risk, they confirm
      an increased risk of PD associated with foods containing animal fat.

PMID- 9918342
TI  - Efficacy and tolerability of tolcapone compared with bromocriptine in levodopa
      treated parkinsonian patients. Tolcapone Study Group.
AB  - The catechol-O-methyltransferase inhibitor tolcapone was compared with the
      dopamine agonist bromocriptine in an open-label, randomized trial involving 146
      levodopa-treated parkinsonian patients with end-of-dose deterioration of
      efficacy. Tolcapone was given at a dosage of 200 mg three times daily;
      bromocriptine was titrated from 1.25 mg once daily at baseline to, at most, 10 mg
      three times daily by day 24 (mean final dose 22.4 mg/day). After 8 weeks, the
      tolcapone group had a significant reduction in daily levodopa dose compared with
      the bromocriptine group (p<0.05). No significant differences in the "on/off" time
      and motor disability were seen between the tolcapone and bromocriptine treatment
      groups. Bromocriptine induced more hallucinations, orthostatic hypotension, and
      nausea, whereas tolcapone therapy was associated with more muscle cramps and
      dystonia. These results suggest that when added to levodopa therapy, the two
      drugs have a different side effect profile, with the advantages for tolcapone
      being absence of titration and quicker efficacy.

PMID- 9918343
TI  - Apomorphine induces changes in GPi spontaneous outflow in patients with
      Parkinson's disease.
AB  - OBJECTIVE: To determine the effect of a single dose of apomorphine on internal
      globus pallidus (GPi) neuronal discharge in patients with Parkinson's disease
      (PD). PATIENTS AND METHODS: Nine PD patients who underwent microelectrode-guided
      posteroventral pallidotomy (PVP) were studied. After identification of a single
      GPi unit discharge with sufficient spike S/N ratio to allow reliable
      thresholding, basal recording was followed by a single 3-mg subcutaneous
      injection. One-minute samples were recorded 10', 30', and 60' after apomorphine.
      RESULTS: In four patients, recording was lost after 5-10 minutes. In two, changes
      were observed at peak-of-dose but recording was then lost, whereas three
      completed recording and returned to baseline, all five showing significant
      reduction in GPi firing rate (mean +/- standard deviation for basal and post
      apomorphine were 143+/-55.6 and 52+/-19.2, respectively; p <0.002). CONCLUSION:
      In patients with PD, apomorphine induces changes in GPi spontaneous discharge and
      modifies firing rates resembling recordings in normal primates. These findings
      show that clinical improvement as well as induction of dyskinesias following DA
      administration could be mediated by reduction of GPi outflow.

PMID- 9918344
TI  - Unilateral radiofrequency lesion versus electrostimulation of posteroventral
      pallidum: a prospective randomized comparison.
AB  - Microelectrode-guided posteroventral pallidotomy (PVP) has shown to be an
      effective method in the treatment of a group of patients with advanced
      Parkinson's disease. A nonlesioning approach by means of deep brain electrodes
      connected to a programmable neuropacemaker has also been used to inhibit the
      internal segment of globus pallidus (posteroventral stimulation [PVS]) reporting
      comparable clinical efficacy to the one obtained with the ablative method.
      Nevertheless, no controlled studies have been performed to compare the efficacy
      of both procedures. A prospective series of 13 patients with a clinical
      indication for globus pallidus surgery was randomized either to a pallidotomy or
      stimulator implantation, and comparisons on motor and neuropsychologic
      measurements were made on a 3-month follow-up basis. Primary measurements of
      efficacy showed a comparable effect on Unified Parkinson's Disease Rating Scale
      and activities of daily living score after both procedures. Secondary
      measurements of efficacy showed that although both techniques improve hand
      tapping score and dyskinesia score, the bilateral improvement in the former was
      greater after PVS whereas the latter improved more significantly after PVP. No
      significant changes in neuropsychologic parameters were observed after either PVP
      or PVS. Side effects and surgery complications occurred in six of 13 patients
      (three after PVP and three after PVS): they were mild, transient, and unrelated
      to optic tract injury. In conclusion, the short-time effect and safety of both
      procedures is comparable.

PMID- 9918345
TI  - Movement and reaction times and fine coordination tasks following pallidotomy.
AB  - The effect of a unilateral, microelectrode-guided lesion in the globus pallidum
      internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced
      Parkinson's disease (PD). The mean age was 60.3+/-9.0 years (range, 40-74) and
      the mean symptom duration was 14.7+/-5.3 years (range, 4-25). In addition to
      clinical ratings, movement time (MT) and reaction time (RT) tests were performed
      at baseline and 3 months after surgery during the "practically defined off" state
      (more than 12 hours after the last dose of levodopa). Improvement occurred
      bilaterally with more robust and statistically significant improvement on the
      contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5%
      (p<0.001) and the choice reaction time (CRT) by 12.2% (p<0.001) when the arm
      contralateral to the pallidotomy side was tested. There was a trend toward
      improvement in the ipsilateral arm. The MT, determined by repetitive movement
      between two adjacent targets, improved by 24% contralaterally (p<0.0001) and by
      12% ipsilaterally (p<0.005). In addition, the Purdue Pegboard (PP) test scores,
      used to evaluate hand dexterity, improved on the contralateral side by 35.5%
      (p<0.0002) but there was no statistically significant ipsilateral improvement. To
      the extent that MT and RT are quantitative measures of bradykinesia, our study
      provides evidence that this parkinsonian feature improves after pallidotomy.

PMID- 9918346
TI  - Movement-related potentials in Parkinson's disease: external cues and attentional
      strategies.
AB  - Hypokinetic movement can be greatly improved in Parkinson's disease patients by
      the provision of external cues to guide movement. It has recently been reported,
      however, that movement performance in parkinsonian patients can be similarly
      improved in the absence of external cues by using attentional strategies, whereby
      patients are instructed to consciously attend to particular aspects of the
      movement which would normally be controlled automatically. To study the
      neurophysiological basis of such improvements in performance associated with the
      use of attentional strategies, movement-related cortical potentials were examined
      in Parkinson's disease and control subjects using a reaction time paradigm. One
      group of subjects were explicitly instructed to concentrate on internally timed
      responses to anticipate the presentation of a predictably timed go signal. Other
      subjects were given no such instruction regarding attentional strategies. Early
      stage premovement activity of movement-related potentials was significantly
      increased in amplitude and reaction times were significantly faster for
      Parkinson's disease subjects when instructed to direct their attention toward
      internally generating responses rather than relying on external cues. It is
      therefore suggested that the use of attentional strategies may allow movement to
      be mediated by less automatic and more conscious attentional motor control
      processes which may be less impaired by basal ganglia dysfunction, and thereby
      improve movement performance in Parkinson's disease.

PMID- 9918347
TI  - Planning and executing an action in Parkinson's disease.
AB  - We evaluated the possible impairment in planning and executing an action in
      patients with Parkinson's disease (PD). The action considered in the present
      study was formed by two successive motor acts: reaching-grasping an object (first
      target) and placing it on a second target of the same shape and size. We examined
      the effects of extrinsic properties of the second target (that is, distance) on
      the various kinematic phases of reaching-grasping movements. Distance, position,
      and size of both stimuli were randomly varied across the experimental session.
      Movements were executed with and without visual control of both targets and arm.
      The performance of six patients with PD was compared with an age-matched control
      group. The kinematics of the initial phase of reaching was influenced by position
      and size of the first target and by distance of the second target in both
      patients and control subjects. In particular, peak acceleration was higher for
      farther position of the second target. However, in the subsequent phase patients,
      differently from control subjects, removed the effects of the second target
      distance by modifying their reaching kinematics. This was obtained by varying the
      duration of the acceleration phase. In summary, the patients reprogrammed the
      reaching component by taking into account only the properties of the first
      target. The decreasing influence of second-target distance on reaching kinematics
      of patients was more evident during movements executed under visual control.
      Moreover, their movements executed without visual control were slowed down from
      the beginning. The second target affected the grasping kinematics only of the
      control subjects. Globally, these results indicate that PD patients are able to
      compute the general program of an action that takes into account extrinsic
      properties of the final target. However, the finding that PD patients
      reprogrammed the movement during its execution suggests a decay of the program
      during its time course, that is, basal ganglia can be involved in storing the
      plan of an action and in controlling its correct execution.

PMID- 9918348
TI  - Remembered saccades with variable delay in Parkinson's disease.
AB  - The effect of increasing delay on the metrics of remembered saccades was studied
      in 10 subjects with mild Parkinson's disease, none of whom was receiving
      treatment with L-dopa, and nine age-matched control subjects. Delays of 1 msec,
      250 msec, 1000 msec, 2500 msec, and 5000 msec were used, and reflexive saccades
      used as a control condition. Results were analyzed for the gain of the primary
      saccade and the accuracy of the final eye position (FEP gain). Reflexive saccades
      were normal in subjects with Parkinson's disease, but remembered saccades showed
      marked hypometria of primary saccade gain at all delays. FEP gain was unimpaired
      in Parkinson's disease, and primary saccade gain and FEP gain did not vary as a
      function of delay. Hypometria of primary saccades is compatible with dysfunction
      in striato-collicular inhibitory pathways in Parkinson's disease, arising as a
      functional consequence of dopamine deficiency in the basal ganglia. Maintenance
      of an accurate FEP gain suggests no deficit in oculomotor spatial working memory
      in Parkinson's disease, at least at delays of up to 5 sec.

PMID- 9918349
TI  - Static and dynamic balance function in spasmodic torticollis.
AB  - The consequences of abnormal head posture on static and dynamic balance skill
      were studied in a group of 10 patients with idiopathic spasmodic torticollis
      (ST). In static conditions, body sway was assessed using a conventional force
      platform with eyes open and with eyes closed. Standardized dynamic balance
      conditions were produced using a rocking platform; lateral and anteroposterior
      dynamic balance skills were assessed by measuring linear displacement both of the
      body base and of the head. Dynamic tests were repeated 6 weeks after botulinum
      toxin treatment in all patients. Patients' results were compared with those
      obtained from 10 control subjects. In static conditions, ST patients did not
      differ from control subjects, but in dynamic conditions, balance parameters were
      greater in the patient group than in the control group. This was true for the
      lateral direction and for dynamic balance parameters recorded both before and
      after botulinum toxin treatment. Eye closure significantly increased dynamic
      balance parameters in both groups. However, the effect of eye closure was greater
      in the patient group than the control group, especially for lateral sway,
      suggesting that patients used vision to compensate for the dynamic balance
      disturbance induced by the spasmodic torticollis. Despite a significant
      improvement of head posture in all patients after botulinum toxin treatment, no
      significant changes in dynamic balance parameters were observed between the first
      and second test. The possible origins of the dynamic balance disturbance observed
      in ST patients are discussed.

PMID- 9918350
TI  - Dystonia in Huntington's disease: prevalence and clinical characteristics.
AB  - BACKGROUND: The prevalence and clinical characteristics of dystonia in
      Huntington's disease (HD) have not been formally assessed. OBJECTIVES: To study
      (1) the prevalence of dystonia in HD in a clinic population, (2) the clinical
      features of dystonia, and (3) clinical correlates of dystonia (for example, age,
      disease duration). METHODS: Patients with HD attending the HD Center at the New
      York State Psychiatric Center were administered the Unified HD Rating Scale and
      underwent a standardized 5.5-minute videotaped examination. Two neurologists
      reviewed the videotaped examination and rated the severity and constancy of
      dystonia, calculating a total dystonia score for each patient. RESULTS:
      Prevalence of dystonia of any severity was 95.2%. Twenty-four of 42 (57.1%) had
      dystonia in at least one body region that was moderate and present more than half
      of the time, and seven of 42 (16.7%) had dystonia that was severe and constant.
      The most prevalent types of dystonia were internal shoulder rotation (64.3%),
      sustained fist clenching (47.1%), excessive knee flexion (42.9%), and foot
      inversion (42.9%). In 37 of 42 (88.1%) patients, there were more than two types
      of dystonia, and in the average patient, three to four types of dystonia. The
      mean severity was between 1 (mild) and 2 (moderate), and the mean constancy was
      between 2 (present less than half of the time) and 3 (present more than half of
      the time). Multivariate linear regression revealed that disease duration (p =
      0.0005) and taking an antidopaminergic agent (p = 0.03) were positively
      associated with the total dystonia score. CONCLUSIONS: The majority of patients
      in this HD clinic exhibited some dystonia. The dystonia was present in several
      body regions and manifested by a variety of movements and postures not typical of
      idiopathic torsion dystonia. The dystonia was not bothersome to most patients,
      and its severity was a function of disease duration and use of an
      antidopaminergic agent.

PMID- 9918351
TI  - Circadian rhythm of periodic limb movements and sensory symptoms of restless legs
      syndrome.
AB  - The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or
      lying and also worsen at night. The current study was designed to determine if
      the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by
      an independent circadian factor. We recorded sleeping and waking PLMs and waking
      sensory symptoms in eight volunteers with RLS for 3 successive nights and days,
      starting with a polysomnographic recording of 2 nights, followed by a third night
      of sleep deprivation and the day after sleep deprivation. This study showed that
      both the PLMs and sensory symptoms were worst at night with a maximum for both
      between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and
      drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of
      sleep deprivation. Circadian temperature curves were normal in all four patients
      with adequate data collection. The highest PLM counts occurred on the falling
      phase of the circadian temperature curve whereas the lowest PLM counts occurred
      on the rising phase of the curve. We conclude that the PLM and sensory symptoms
      in RLS are influenced by a circadian rhythm, and that the "worsening at night"
      criterion of the RLS Definition Criteria is, at least in part, distinct from the
      "worsening while lying or sitting" criterion.

PMID- 9918352
TI  - Studies of penetrance and anticipation in five autosomal-dominant restless legs
      syndrome pedigrees.
AB  - Restless legs syndrome (RLS) can occur with an autosomal-dominant mode of
      inheritance. To determine if there are distinguishing features of RLS pedigrees
      which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81
      affected members were analyzed for age of onset, sex ratio, and transmission
      pattern. One-factor analysis of variance of ages of onset between generations was
      carried out, and segregation ratios were calculated for each generation. These
      kindreds showed an autosomal-dominant mode of inheritance and a male:female ratio
      of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of
      reduced penetrance. In two of the five analyzed pedigrees, there is statistical
      support for anticipation (p<0.05). These variations in penetrance and
      anticipation suggest possible genetic heterogeneity.

PMID- 9918353
TI  - Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson's
      disease.
AB  - In a series of consecutively randomized outpatients who had Parkinson's disease
      (PD), we examined the association of three behaviors: sleep fragmentation,
      altered dream phenomena, and hallucinations/illusions. Using a log-linear model
      methodology, we tested the independence of each behavior. Sixty-two percent of
      the subjects had sleep fragmentation, 48% had altered dream phenomena, and 26%
      had hallucinations/illusions. Eighty-two percent of the patients with
      hallucinations/illusions experienced some form of sleep disorder. The three
      phenomena were not independent. The interaction between sleep fragmentation and
      altered dream phenomena was strongly statistically significant. Likewise, a
      significant interaction existed between altered dream phenomena and
      hallucinations/illusions. No interaction occurred between sleep fragmentation and
      hallucinations/illusions. Sleep fragmentation, altered dream phenomena, and
      hallucinations/illusions in PD should be considered distinct but often
      overlapping behaviors. The close association between altered dream phenomena and
      hallucinations suggests that therapeutic interventions aimed at diminishing dream
      related activities may have a specific positive impact on hallucinatory behavior.

PMID- 9918354
TI  - Parkinsonism after a wasp sting.
AB  - A 49-year-old man had mild parkinsonism after being stung by a wasp, a member of
      the Hymenoptera order. His clinical course was stable for 6 months after which
      his condition rapidly progressed to a severe akinetic-rigid syndrome with
      evidence, on a magnetic resonance imaging brain scan, of marked destruction of
      the basal ganglia. The symptoms did not respond to standard antiparkinsonian
      medications. Repeated courses of plasmapheresis followed by monthly intravenous
      infusions of immunoglobulin and long-term administration of azathioprine halted
      and appeared to partially reverse his deterioration. The literature on the
      neurologic, particularly the extrapyramidal, manifestations of stings by insects
      of the Hymenoptera order is reviewed and the possible pathophysiological
      mechanisms of injury are discussed. Hymenoptera stings should be included in the
      differential diagnosis of acute and chronic extrapyramidal syndromes.

PMID- 9918355
TI  - Pilot study with clozapine in patients with HIV-associated psychosis and drug
      induced parkinsonism.
AB  - Clozapine (CZP) is an atypical antipsychotic drug that does not appear to block
      striatal dopamine receptors. In six patients who met the criteria of HIV
      associated psychosis and who had previously developed moderate parkinsonism as a
      result of the use of typical neuroleptic agents, CZP was added in an open, rising
      dose study. Subjects were evaluated at baseline after at least 7 days without
      neuroleptic drugs and then monthly for 3 months of the experimental treatment
      using three rating scales: Brief Psychiatric Rating Scale (BPRS), Clinical Global
      Impression (CGI), and motor examination of the Unified Parkinson's Disease Rating
      Scale (UPDRS). A significant reduction in psychopathology as represented in the
      BPRS total score (54.2 at baseline versus 23.9 at month 3) and CGI (2 and 8,
      respectively) was obtained with a mean CZP dose of 27.08 mg/day. Parkinsonism
      also improved by an average of 76.5% at the end of the study. One patient did not
      complete the study as a result of a progressive decrease in leukocyte count while
      on CZP. These preliminary results suggest that the pharmacologic properties of
      CZP may be of value in the management of HIV-psychotic patients.

PMID- 9918356
TI  - PET imaging of the pre-synaptic dopamine uptake sites in rapid-onset dystonia
      parkinsonism (RDP).
AB  - BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement
      disorder characterized by abrupt onset over hours to days of bradykinesia,
      postural instability, dysphagia, dysarthria, and severe dystonic spasms with
      decreased levels of the dopamine metabolite, homovanillic acid (HVA), in
      cerebrospinal fluid (CSF). METHODS: We imaged the dopamine re-uptake system with
      [O-methyl-11C]beta-CFT ([11C]beta-CFT) in three severely affected individuals
      with RDP and four patients with idiopathic Parkinson's disease (IPD). Results
      were compared with those of age-matched normal volunteers. RESULTS: Positron
      emission tomography images from those patients with IPD demonstrated a dramatic
      reduction in the volume of distribution of [11C]beta-CFT whereas patients with
      RDP showed slightly elevated values. CONCLUSIONS: The data suggest that patients
      with RDP do not have a decrease in the number of dopamine re-uptake sites. Our
      findings suggest that, unlike the situation in IPD, low CSF HVA concentrations
      seen in RDP patients are not the result of degeneration of striatal dopamine
      terminals or loss of dopamine re-uptake sites.

PMID- 9918357
TI  - Ropinirole for restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a common and underdiagnosed condition that
      results in a desire to move the extremities often associated with
      paresthesia/dysesthesia, motor restlessness, worsening of symptoms at rest with
      at least temporary relief by activity, and worsening of symptoms in the evening
      or night. We tested the new dopamine agonist ropinirole in 16 patients with RLS
      in an open-label trial. The mean daily dose was 2.8+/-2.3 mg (range, 0.5-12.0).
      The 13 patients who completed the study reported a 58.7% improvement (p = 1.08 x
      10(-8)) as judged by the abbreviated International Restless Legs Study Group
      questionnaire. Three patients discontinued the medication secondary to adverse
      events (rash and nervousness) and other extenuating circumstances. These
      encouraging preliminary results justify larger and more controlled trials of
      ropinirole in patients with RLS.

PMID- 9918358
TI  - Positron emission tomographic studies in restless legs syndrome.
AB  - We studied six restless legs syndrome (RLS) patients with [F18]fluorodeoxyglucose
      (FDG) positron emission tomography (PET). We also studied four of these same
      patients with [F18]fluorodopa (FDOPA) PET. The patients' FDG and FDOPA PET scans
      were compared with those from age-matched healthy control subjects. No
      significant differences between the two groups were found for any regional blood
      flow values derived from the FDG scans or for any binding constants derived from
      the FDOPA scans. These results suggest that any abnormal resting brain metabolic
      activity or putative presynaptic dopaminergic defect in RLS is likely either to
      be so subtle that it is below the threshold for ready detection by PET or that it
      is located in an area of neural tissue inaccessible to the current scanner. No
      substantial defect is likely to involve the dopaminergic nigrostriatal axis.

PMID- 9918359
TI  - A child with recurrent episodes of involuntary movements.

PMID- 9918360
TI  - Do serotonin reuptake inhibitor antidepressants worsen Parkinson's disease? A
      retrospective case series.

PMID- 9918361
TI  - Safety of transcranial magnetic stimulation in patients with implanted deep brain
      stimulators.

PMID- 9918362
TI  - Levodopa therapy can ameliorate tetrabenazine-induced parkinsonism.

PMID- 9918363
TI  - Parkinsonism as a result of a giant aneurysm.

PMID- 9918364
TI  - Catatonia responsive to lorazepam: a case report.

PMID- 9918365
TI  - Ideomotor apraxia in progressive supranuclear palsy: a case study.

PMID- 9918366
TI  - Progressive, asymmetric cortical visual disturbances and movement disorders in
      two patients.

PMID- 9918367
TI  - The eye of the tiger sign in cortical-basal ganglionic degeneration.

PMID- 9918368
TI  - French horn embouchure dystonia.

PMID- 9918369
TI  - Mexiletine in the treatment of blepharospasm: experience with the first three
      patients.

PMID- 9918370
TI  - Meige's syndrome in a patient treated with ranitidine.

PMID- 9918371
TI  - Paroxysmal dystonia in Behcet's disease.

PMID- 9918372
TI  - Essential palatal tremor: evidence of heterogeneity based on clinical features
      and response to Sumatriptan.

PMID- 9918373
TI  - Hereditary chin tremor/myoclonus: a report from Latin America.

PMID- 9918374
TI  - Stimulus-sensitive spinal segmental myoclonus improved with injections of
      botulinum toxin type A.

PMID- 9918375
TI  - Pathologic laughter resulting from a large midbrain arteriovenous malformation.

PMID- 9918376
TI  - Delayed onset of hand tremor related to cerebellar hemorrhage.

PMID- 9918377
TI  - Rubral tremor associated with cavernous angioma of the midbrain.

PMID- 9918378
TI  - Pregnancy in Parkinson's disease: a review of the literature and a case report.

PMID- 9918379
TI  - Cervical stenosis and dystonic cerebral palsy.

PMID- 9918380
TI  - Proliferation of pancreatic islet-cells in cyclic and pregnant rats after
      treatment with progesterone.
AB  - The effect of progesterone (P) on pancreatic islet-cell proliferation and
      function of cyclic and pregnant rats was investigated in vivo. Silastic tubes
      containing P were inserted s.c. in cyclic rats for 7 or 14 days and in pregnant
      rats from day 7 to 14, from day 14 to 21 or from day 7 to 21 of pregnancy. 5
      Bromo-2-deoxyuridine (BrdU) was infused during the last 24h of the treatment; the
      proportion of dividing islet-cells was determined in pancreatic sections, which
      were immunostained for BrdU. Islet-cell function was determined by measuring
      glucose and insulin response to a standard intravenous glucose challenge. P
      treatment increased P and 20alpha-dihydroprogesterone (20alpha-OHP) levels in
      cyclic rats; in pregnant rats, only the plasma levels of 20alpha-OHP were
      elevated. Both 7 and 14 days of P treatment stimulated islet-cell proliferation
      in cyclic rats. In pregnant rats, P treatment increased islet-cell proliferation
      on day 14, but not on day 21 after either 7 or 14 days of P treatment. P did not
      affect plasma lactogenic activity in pregnant rats; plasma concentrations of
      prolactin were decreased after 14 days of P treatment in cyclic rats, but were
      not affected in pregnant rats. P treatment had no effect on glucose tolerance and
      glucose-stimulated insulin secretion in any of the groups. It was concluded that:
      1. in vivo P stimulates islet-cell proliferation, but does not affect islet-cell
      function, 2. the stimulatory effects of P are indirect and possibly mediated by
      the P metabolite 20alpha-OHP and 3. at the end of gestation, stimulation of islet
      cell proliferation is inhibited by some factor, which is not identical to P.

PMID- 9918381
TI  - Cloning of Rab GTPases expressed in human skeletal muscle: studies in insulin
      resistant subjects.
AB  - To explore the potential role of Rab GTPases in human insulin resistance, we
      first employed a PCR-cloning approach to identify Rab isoforms that are expressed
      in human skeletal muscle. Multiple Rab isoforms including Rab1A, Rab4A, Rab5B,
      Rab7, Rab8, Rab10, Rab12A, Rab13, Rab18, Rab21, and Rab22 mRNA were found to be
      expressed in human skeletal muscle. The second goal was to examine whether mRNA
      expression for Rabs targeted to endocytotic/exocytotic compartments was altered
      as a function of insulin resistance. Quantitative PCR analysis demonstrated that
      Rab4A, Rab5B and Rab18 mRNA levels in skeletal muscle from insulin-resistant
      patients without (IR) and with non-insulin-dependent diabetes mellitus (NIDDM)
      were not significantly different from those in insulin-sensitive controls (IS).
      At the protein level, total Rab5B amount was not significantly different among
      IS, IR and NIDDM subgroups. However, in basal muscle, Rab5B in the total membrane
      fraction was 2.1-3.6 fold higher in IR and NIDDM than in IS subjects. Insulin
      increased membrane-associated Rab5B by 3-fold in IS subjects, whereas this effect
      was not significant in both IR and NIDDM subgroups. Thus, for the first time, we
      have comprehensively studied the mRNA expression of Rab isoforms in human muscle.
      The phlethora of Rab GTPases are indicative of high volume of vesicular traffic
      and regulated metabolism. The potential role of specific Rab isoforms in insulin
      resistance does not rely on a change in steady state mRNA levels, but is
      demonstrable as an alteration in protein subcellular distribution and
      trafficking.

PMID- 9918382
TI  - Mechanism of the diabetogenic action of cyclosporin A.
AB  - To investigate the mechanism of diabetogenic action of cyclosporin A (CsA), 7
      male Wistar albino rats received 10 mg/kg/day of the drug for 4 weeks (CsA). The
      results were compared with controls (C); blood CsA levels measured weekly
      remained stable throughout the experiment (mean +/- SEM) (X = 2657.9+/-155.1
      ng/ml). Intravenous glucose load (0.75 g/kg) performed after 2 weeks of CsA
      therapy showed glucose intolerance in treated animals as evaluated by the glucose
      area under the curve (CsA = 409.2+/-17.8 vs. C = 313.3+/-12.6 umol x ml(-1) x
      min(-1)) (p < 0.05) with insulin levels being similar in the two groups (CsA =
      8603.9+/-1645.5 vs. C = 9571.9+/-828.5 pmol x ml(-1) x min(-1)). After 4 weeks of
      CsA administration, glucose intolerance was maintained (CsA = 398.6+/-35.6 vs. C
      = 301.7+/-23.0 umol x ml(-1) x min(-1)) (p < 0.05) associated with a significant
      decrease in insulin secretion (CsA = 4404.9+/-2392.0 vs. C = 10075.9+/-2861.0
      pmol x ml(-1) x min(-1) (p < 0.05). These results suggest that CsA induced a
      state of insulin resistance preceding the failure of insulin secretion. After 4
      weeks, the pancreatic insulin content was also decreased (CsA = 0.7+/-0.1 vs. C =
      1.4+/-0.5 mU/mg) (p < 0.05). Maximal insulin binding to isolated adipocytes was
      not affected by CsA (CsA = 7.4+/-2.6 vs. C = 6.4+/-2.0%), although glucose
      transport and oxidation decreased after CsA treatment (p < 0.05). In conclusion,
      glucose intolerance induced by CsA in Wistar albino rats is due to decreased
      insulin production and impaired insulin action by a post-binding mechanism.

PMID- 9918383
TI  - Age-related responses of vasoactive factors during acute exercise.
AB  - To evaluate the age-related response of vasoactive factors during acute exercise,
      young (n = 8, aged 23.6+/-2 years) and old (n = 13, aged 77+/-6 years) healthy
      volunteers performed a stress test using a treadmill, and blood samples were
      taken before and after exercise. There were neither basal (old people 77+/-53 vs.
      young people 67.6+/-40 pg/ml) nor peak exercise-related (old people 77+/-43 vs.
      young people 66.8+/-34 pg/ml) differences in plasma adrenomedullin (AM) between
      both groups. AM did not increase with exercise in either group. Regarding plasma
      cAMP, there were neither basal nor exercise related differences, but this
      nucleotide increased with exercise in both groups (old people p < 0.0001, young
      people p < 0.05). Plasma Atrial Natriuretic Peptide (ANP) was higher in basal
      (116.3+/-64 vs. 46.8+/-21 pg/ml, p < 0.003) and after exercise samples (150.2+/
      76.5 vs. 68.7+/-29.5 pg/ml, p < 0.004) in old people as compared with young
      people. Old people showed an increase in ANP with exercise (p < 0.05), but in
      young people, though there was a trend to increase, it did not reach statistical
      significance. There were neither basal nor exercise related differences in plasma
      cGMP, but this nucleotide increased with exercise in both groups. Angiotensin II
      (AT-II) levels were lower in basal and after exercise samples in old people as
      compared with young people. AT-II levels did not increase with exercise in either
      group. These data suggest that, with increasing age, the vascular tree develops
      resistance to ANP and higher sensitivity to AT-II, while AM levels do not change.
      Exercise makes ANP changes more evident, while AM and AT-II are not modified.

PMID- 9918384
TI  - Beneficial effect of long-term combined treatment with voglibose and pioglitazone
      on pancreatic islet function of genetically diabetic GK rats.
AB  - Effects of voglibose (an alpha-glucosidase inhibitor) and pioglitazone (an
      insulin sensitizer) on glycemic control and on the function of pancreatic islets
      were evaluated using Goto-Kakizaki (GK) rats with non-insulin-dependent diabetes
      mellitus (NIDDM). Five week administration (8-13 weeks of age in GK rats) of
      voglibose alone (added to the chow at a concentration of 10 ppm), pioglitazone
      alone (10 mg/kg daily p.o.), or both of the agents together significantly
      improved fasting plasma glucose levels and those at 120 min in oral glucose
      tolerance tests. Insulin secretory capacity in response to glucose of the
      isolated islets, assessed by batch incubation, was significantly improved in the
      voglibose and in the voglibose plus pioglitazone groups. Eight-week
      administration (5-13 weeks of age) of voglibose and voglibose plus pioglitazone
      successfully lowered the fasting levels of plasma glucose and triglyceride. The
      glucose-responsiveness in insulin release from the islets was also significantly
      recovered by the therapy. The treatment increased the insulin content of the
      islets to almost twice that in untreated controls. Thus, treatment by these drugs
      can not only effectively ameliorate the metabolic derangement of NIDDM in GK
      rats, but it can also restore the deteriorated islet function, possibly through
      protection from glucose toxicity.

PMID- 9918385
TI  - Potentiation of glucose-induced insulin secretion by fagomine, a pseudo-sugar
      isolated from mulberry leaves.
AB  - The mechanisms of potentiation by fagomine, an N-containing pseudo-sugar derived
      from mulberry leaves, of insulin secretion from isolated rat pancreatic islets in
      response to glucose was studied. Fagomine at more than 1 mmol/L significantly
      potentiated insulin secretion induced by 10 mmol/L glucose. The pseudo-sugar,
      however, did not affect the basal insulin secretion assessed at a glucose
      concentration of 3.5 mmol/L. The effects of fagomine on 10 mmol/L and 20 mmol/L
      glucose-induced insulin secretion were not significantly different. Fagomine (4
      mmol/L) also potentiated glyceraldehyde-induced insulin secretion, but not the
      leucine-induced type. Glycolysis assessed by lactate production from glucose was
      significantly enhanced. The amounts of all intermediates (from glucose 6
      phosphate to glyceraldehyde 3-phosphate) of the upper part of the glycolytic
      pathway in islets incubated with 20 mmol/L glucose were not affected by 4 mmol/L
      fagomine. The rise in the ATP/ADP ratio through both the glycolytic pathway and
      the citric acid cycle is believed to be pivotal in glucose- and glyceraldehyde
      induced insulin secretion; whereas the ATP/ADP ratio rise through the citric acid
      cycle via the formation of acetyl-CoA is involved in leucine-induced insulin
      secretion. Our findings, together with these considerations, suggest that
      fagomine potentiates glucose-induced insulin secretion through acceleration of
      some step(s) after the formation of glyceraldehyde 3-phosphate in the glycolytic
      pathway.

PMID- 9918386
TI  - Importance of phosphodiesterase 3 for the lipolytic response in adipose tissue
      during insulin-induced hypoglycemia in normal man.
AB  - The present investigation aimed to clarify the role of phosphodiesterase (PDE)
      type 3 for in vivo lipolysis in human adipose tissue during simultaneous insulin
      and catecholamine stimulation. Therefore, ten healthy subjects were investigated
      during insulin-induced hypoglycemia. Microdialysis probes were implanted in the
      subcutaneous adipose tissue and perfused by solvents with or without addition of
      the specific PDE 3 antagonist amrinone. Furthermore, changes in the local blood
      flow surrounding the dialysis probes were assessed by the ethanol escape
      technique. During the 60 min period before the start of the insulin infusion,
      adipose tissue glycerol levels (lipolysis index) increased significantly when
      amrinone was added to the perfusate (p = 0.0006, one-factor ANOVA). The
      antilipolytic response to the early phase of insulin infusion decreased (delta
      glycerol 9.0+/-3.5 vs. 29.9+/-6.0 micromol/l, p = 0.04) and the lipolytic
      response after hypoglycemia increased (AUC 122.4+/-18.0 vs. 13.4+/-16.3 micromol
      x l(-1) x h, p = 0.0001) comparing the experiments with or without amrinone,
      respectively. When amrinone was excluded from the perfusate, there was an
      increase in the nutritive blood flow during hypoglycemia, whereas there were no
      significant changes in the local blood flow surrounding the probe when amrinone
      was added to the perfusate. In conclusion, during insulin-induced hypoglycemia,
      PDE 3 activation clearly counteracts the lipolytic effect of catecholamines. When
      PDE 3 is specifically blocked, lipolysis increases greatly. Thus, PDE 3 is
      important for the in vivo regulation of the antilipolytic and lipolytic responses
      to hormones in human adipose tissue.

PMID- 9918387
TI  - Maternal thyroid function in multiple pregnancy: the variable thyrotropic
      activity of human chorionic gonadotropin.
AB  - The present study was undertaken to evaluate thyroid function and thyrotropic
      action of hCG in multiple pregnancy. We examined serum samples from 9 multiple
      pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as
      control subjects. Serum hCG levels in multiple pregnancy were higher than those
      in singleton pregnancy in the second and third trimesters (P < 0.01). The mean
      free T3 and T4 concentrations in multiple pregnancy did not differ from those in
      singleton pregnancy in each trimester. Serum hCG levels showed a statistically
      significant positive correlation with free T3 and T4 levels in singleton
      pregnancy (P < 0.001). However, these correlations were not observed in multiple
      pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in
      FRTL-5 cells in multiple pregnancy sera was significantly higher than that in
      singleton pregnancy in the first trimester (P < 0.05), but did not differ in the
      second and third trimesters. Moreover, TSA did not show any correlation with
      serum hCG levels in multiple pregnancy in contrast with the results in normal
      pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was
      lower than in singleton pregnancy in the second and third trimesters. The
      discrepancy between immunoreactivity and thyrotropic activity of hCG may be
      caused by the variable thyrotropic potency of heterogeneous hCG molecules in
      multiple pregnancy.

PMID- 9918389
TI  - Bioprobes for investigating mammalian cell cycle control.
AB  - Bioprobes are low molecular weight compounds which are useful for investigating
      mammalian cell functions. The use of bioprobes has substantially assisted the
      investigation of complex biochemical processes of the mammalian cell cycle. In
      this review, cell cycle inhibitors mainly isolated from the microorganism are
      described and their possibility as an antitumor agents is considered. Most cancer
      cells have some abnormality in the control mechanism of cell cycle progression.
      Cyclin-dependent kinases (Cdk), which are activated by the binding with the
      cyclin and simultaneously by the phosphorylation/dephosphorylation of itself,
      play important roles as engines in the cell cycle. Tubulins are considered to be
      one of the most important proteins of the cell division machinery. Therefore, Cdk
      inhibitors and tubulin binders are possible anticancer drugs. Since the function
      of proteins controlling the cell cycle is also regulated by phosphorylation and
      dephosphorylation, inhibitors of protein kinases and phosphatases are considered
      as possible an antitumor agents. We expect that some bioprobes will be developed
      for clinical use.

PMID- 9918388
TI  - Electrocardiographic changes during insulin-induced hypoglycemia in healthy
      subjects.
AB  - Hypoglycemia is associated with alterations of the ECG, a phenomenon which might
      be used for the development of a hypoglycemia detection device. We investigated
      the reproducibility and magnitude of ECG alterations during insulin-induced
      hypoglycemia in nine healthy volunteers. The subjects were studied twice with an
      identical study protocol on two different study days. During hypoglycemia
      frequent ECG recordings were done with a conventional 12 lead ECG. S.c. injection
      of 0.15 U/kg of regular insulin induced a fourfold increase in insulinemia on
      both study days as well as a mean decline in blood glucose by 1.6 mmol/l to a
      minimum of 2.8 mmol/l within 60 min after injection. Blood potassium levels
      declined by a mean of 0.25 mmol/l to minimal values of 3.69 mmol/l. On both study
      days, a progressive flattening of the T-waves was observed during the
      experiments. R-waves remained constant leading to an increase in RT ratios by at
      least 50% in comparison to baseline values. These changes were most pronounced in
      leads I, V3, V5 and V6. The magnitude and reproducibility of the observed ECG
      changes during hypoglycemia may allow the development of a hypoglycemia detection
      device.

PMID- 9918390
TI  - Erinacine E as a kappa opioid receptor agonist and its new analogs from a
      basidiomycete, Hericium ramosum.
AB  - A kappa opioid receptor binding inhibitor was isolated from the fermentation
      broth of a basidiomycete, Hericium ramosum CL24240 and identified as erinacine E
      (1). Three analogs of 1 were produced by fermentation in other media and by
      microbial biotransformation. Of these compounds, 1 was shown to be the most
      potent binding inhibitor. Preliminary SAR studies of these compounds indicated
      that all functional groups and side chains were required for the activity.
      Compound 1 was a highly-selective binding inhibitor for the kappa opioid
      receptor: 0.8 microM (IC50) for kappa, >200 microM for mu, and >200 microM for
      delta opioid receptor. Compound 1 suppressed electrically-stimulated twitch
      responses of rabbit vas deferens with an ED50 of 14 microM. The suppression was
      recovered by adding a selective kappa opioid receptor antagonist nor
      binaltorphimine, indicating that 1 is a kappa opioid receptor agonist.

PMID- 9918392
TI  - Topostatin, a novel inhibitor of Topoisomerases I and II produced by
      Thermomonospora alba strain No. 1520. II. Physico-chemical properties and
      structure elucidation.
AB  - Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of
      Thermononospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and
      II, and it has neither ability to stabilize the cleavable complex nor ability to
      intercalate into DNA strands. The molecular formula of topostatin was determined
      as C36H58N4O11S based on the FAB-MS analyses, and the structure was elucidated to
      be a novel 14-membered ring containing peptide and terpenoid by various NMR
      spectroscopies.

PMID- 9918391
TI  - Topostatin, a novel inhibitor of topoisomerases I and II produced by
      Thermomonospora alba strain No. 1520. I. Taxonomy, fermentation, isolation and
      biological activities.
AB  - A novel inhibitor of topoisomerases designated as topostatin was isolated from
      the culture filtrate of Thermomonospora alba strain No. 1520. Topostatin
      inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase
      I, and also inhibited the relaxation of supercoiled pBR322 DNA and decatenation
      of kinetoplast DNA by human placenta topoisomerase II. Topostatin had neither
      ability to stabilize the cleavable complex nor ability to intercalate into DNA
      strands. The inhibitor exhibited growth inhibitory activity against the tumor
      cells (SNB-75 and SNB-78) of central nervous system, but did not exhibit any
      antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts
      and fungi.

PMID- 9918393
TI  - New brominated and halogen-less derivatives and structure-activity relationship
      of azaphilones inhibiting gp120-CD4 binding.
AB  - Novel brominated and halogen-less azaphilone (oxoisochromane) derivatives, 5
      bromoochrephilone and dechloroisochromophilone IV, and known derivatives,
      dechloroisochromophilone III and isorotiorin, were isolated from the culture
      broth of a producing organism of isochromophilones I and II (azaphilones
      inhibiting gp120-CD4 binding), Penicillium multicolor FO-2338, fermented in a
      medium containing potassium bromide. Nineteen azaphilone-related compounds
      isolated from the above strain and from other fungi were tested for the
      inhibition of gp120-CD4 binding and the structure-activity relationship is
      discussed. Consequently, 5-bromoochrephilone is the strongest inhibitor (IC50,
      2.5 microM). A halogen atom at C-5, a proton at C-8 and a diene structure in C-3
      side chain of 6-oxoisochromane ring are necessary for gp120-CD4 binding.

PMID- 9918394
TI  - Novel inhibitors of fungal protein synthesis produced by a strain of Graphium
      putredinis. Isolation, characterisation and biological properties.
AB  - The isolation and structure determination of 6 analogues of the fungal protein
      synthesis inhibitor GR135402, from Graphium putredinis, is described. The
      relative potencies of the compounds as protein synthesis inhibitors and as in
      vitro antifungal agents provide interesting insights into the structure-activity
      relationships in this series.

PMID- 9918395
TI  - Structures and biosynthesis of aflastatins: novel inhibitors of aflatoxin
      production by Aspergillus parasiticus.
AB  - Two novel inhibitors of aflatoxin production by Aspergillus parasiticus were
      isolated from the mycelial extracts of Streptomyces sp. MRI142 and termed
      aflastatin A and B. The structures of aflastatin A (1) and B (5) were elucidated
      by NMR and chemical degradation experiments. These compounds have a novel
      skeleton of a tetramic acid derivative with a highly oxygenated long alkyl chain.
      The incorporation experiments using 13C-labeled acetates, propionate, glucose and
      glycolate suggested that most of the C2 and C3 units involved in the alkyl chain
      moiety of aflastatin A were biosynthesized from acetic and propionic acids, but
      five C2 units in the alkyl chain originated from glycolic acid.

PMID- 9918396
TI  - Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL
      2338 pIG1. I. Fermentation, isolation and biological activity.
AB  - In a previous report, a plasmid, pIG1, which contained the loading domain from
      the Streptomyces avermitilis polyketide synthase (PKS), promoters from
      Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora
      erythraea, was integrated into the S. erythraea chromosome, effectively replacing
      the natural erythromycin loading domain with the avermectin loading domain. In
      this paper, we report the feeding of short-chained fatty acids to this
      recombinant strain, and its parent, NRRL 2338. Both strains incorporated
      exogenously supplied fatty acids to produce novel, biologically active, C-13
      substituted erythromycins.

PMID- 9918397
TI  - Fattiviracin A1, a novel antiviral agent produced by Streptomyces microflavus
      strain No. 2445. II. Biological properties.
AB  - Fattiviracin A1, showed potent antiviral activities against herpes simplex virus
      type 1 (HSV-1), varicella-zoster virus (VZV), influenza A virus and human
      immunodeficiency virus type 1 (HIV-1). It showed no cytotoxicity against Vero
      cells. Fattiviracin A1 exhibited no significant antibacterial or antifungal
      activities. Treatment of HSV-1 with fattiviracin A1 decreased its infectivity to
      Vero cells. The mechanism of its antiviral activity may be due to inactivation of
      the viral particles and inhibition of viral entry into host cells.

PMID- 9918398
TI  - Discovery of new homologous pamamycins by mass spectrometry and post mortem
      inhibitory action on autolysis of chicken embryo chorioallantoic membrane blood
      vessels.

PMID- 9918399
TI  - S19159, a modulator of neurite outgrowth produced by the ascomycete Preussia
      aemulans. II. Structure elucidation.

PMID- 9918400
TI  - The structures of pyridovericin and pyridomacrolidin, new metabolites from the
      entomopathogenic fungus, Beauveria bassiana.

PMID- 9918401
TI  - Isolation and structure of peptaibolin, a new peptaibol from Sepedonium strains.

PMID- 9918402
TI  - Improved protection against Venezuelan equine encephalitis by genetic engineering
      of a recombinant vaccinia virus.
AB  - An improved vaccine is needed against Venezuelan equine encephalitis (VEE) virus
      because the existing live attenuated vaccine, TC-83, causes a high incidence of
      adverse effects, and the Formalin-inactivated vaccine, C-84, does not protect
      against airborne infection. A recombinant vaccine had previously been constructed
      in which the VEE structural proteins were expressed by vaccinia virus. Although
      protection against subcutaneous challenge with VEE was achieved, the vaccine had
      limited efficacy against aerosolized virus. We made a similar construct (WR100)
      and compared its performance with that of a recombinant vaccinia virus which had
      been altered in two ways (WR103) in order to improve its performance as a
      vaccine: a synthetic promoter was inserted upstream of the VEE coding sequence to
      increase the amount of VEE proteins produced, and a single nucleotide in the E2
      glycoprotein gene was altered to enhance immunogenicity. The WR103 virus
      expressed greater amounts of VEE proteins on the surface of infected cells than
      did WR100, and this difference was found to correspond to a 3.5-fold increase in
      VEE protein production. Sera from mice immunized with WR103 contained elevated
      levels of antibody to VEE, and enhanced protection against subcutaneous challenge
      with the pathogenic Trinidad donkey strain was achieved. This altered construct
      could form the basis for a better vaccine against VEE.

PMID- 9918403
TI  - Presence of HLA-C-restricted cytotoxic T-lymphocyte responses in long-term
      nonprogressors infected with human immunodeficiency virus.
AB  - Approximately 5% of people with human immunodeficiency virus type 1 (HIV-1)
      infection remain free of disease for 10 or more years. These long-term
      nonprogressors (LTNPs) exhibit lower viral loads and stable CD4+ lymphocyte
      counts. The immunologic basis for this disease-free condition is not known.
      Because cytotoxic T lymphocytes (CTLs) constitute a major immune defense
      mechanism for sustained recovery from viral infections, we analyzed HIV-specific
      CTL responses in three asymptomatic LTNPs. We observed the presence of HIV-1
      envelope-specific CTL responses mediated by HLA class I C-restricted CD8+ cells
      in these individuals. Using autologous target cells and a panel of HLA-matching
      and -mismatching B-cell lines as targets, we determined that HLA-Cw7 is the
      restricting element for the observed CTL activity. Additionally, we identified
      three peptides, one previously not reported, from conserved regions in the
      envelope protein as CTL epitopes. We previously reported these peptides to be
      efficient in inducing HIV-specific cellular immune responses in murine and
      nonhuman primate models. Our results support the role of the HLA-C locus in
      generating CTL responses and constitute the first report of an HLA-Cw7-restricted
      HIV-1 envelope-specific CTL response in HIV+ LTNPs, which may be important in the
      control of HIV replication in vivo.

PMID- 9918404
TI  - Immunization with the N-terminal region of the nonstructural protein NS1 promotes
      survival after challenge with lethal influenza A virus dose.
AB  - We previously reported that the epitope recognized by an influenza A virus H1,
      H2, and H3-crossreactive, H-2 Ld-restricted CD8+ cytotoxic T lymphocyte (CTL) is
      located between amino acids 1 and 40 on the nonstructural protein NS1. In the
      present experiments, we examined whether immunization with recombinant vaccinia
      virus which contained genes coding for amino acids 1-40 of NS1 (Vac-10) protected
      mice from lethal challenge with influenza A virus. Mice immunized with this
      recombinant virus developed influenza A virus-specific cytotoxic activity but not
      neutralizing antibodies. Challenge with a lethal dose of influenza A virus
      demonstrated that the first deaths were delayed by 2 days, and the mortality rate
      was significantly reduced (p < 0.05) in Vac-10-immunized mice compared with mice
      immunized with control vaccinia virus. These results suggest that immunization
      with a single subtype-crossreactive CTL epitope on NS1 can induce protective
      immunity against lethal influenza A virus infection.

PMID- 9918405
TI  - Costimulatory activity of inactivated influenza virus in response of human
      peripheral blood mononuclear cells to phytohemagglutinin A and anti-CD3 antibody.
AB  - We tested the effect of inactivated influenza A virus on the response of human T
      lymphocytes to several stimuli. Our results demonstrate that the response to both
      phytohemagglutinin A (PHA) and anti-CD3 was substantially enhanced by pre
      exposure of peripheral blood mononuclear cells (PBMC) to heat-inactivated viral
      particles, whereas no effect was noted on the proliferative response of PBMC to
      IL-2. In addition to cell proliferation, exposure of PBMC to viral particles
      increased the secretion of interferon (IFN)-gamma during stimulation with anti
      CD3 antibody and PHA. The costimulatory effect of influenza A virus was reduced
      by 40% in the presence of 0.1 mM sialic acid. The possible mechanisms involved in
      the costimulatory effects of influenza A virus are discussed.

PMID- 9918406
TI  - A synthetic peptide from the first conserved region in the envelope protein gp160
      is a strong T-cell epitope in HIV-infected chimpanzees and humans.
AB  - We reported earlier that synthetic peptides corresponding to highly conserved
      regions in the envelope protein gp160 of the human immunodeficiency virus type 1
      (HIV-1), in particular an 11-amino acid sequence (peptide 104) from the first
      conserved region at the amino-terminus, were capable of inducing strong HIV
      specific T-cell proliferative responses in several inbred mouse strains as well
      as in outbred Rhesus monkeys. We have now obtained evidence of the presence of
      significant levels of proliferative response to peptide 104 in 7 of 9 chimpanzees
      chronically infected with HIV-1 (p < or = 0.05) and 8 of 17 HIV+ individuals (p <
      or = 0.001). Further, four other conserved HIV envelope-derived peptides,
      identified previously in our murine and Rhesus monkey model systems, were widely
      recognized as T-cell epitopes in both chimpanzees and humans infected with HIV-1.
      In none of the infected subjects did peripheral blood mononuclear cells show
      proliferative responses to unrelated control peptides. Also, neither the control
      normal chimpanzees nor HIV-seronegative individuals showed proliferative
      responses to the conserved peptides. With respect to the humoral responses, serum
      samples from none of the chimpanzees showed reactivity with any of the conserved
      peptides, and only low levels of antibody responses against peptide 104 were
      observed in 3 of the 17 patients (p > 0.05). Importantly, three of the conserved
      envelope-derived peptides, including peptide 104, overlap with sequences that
      were reported in the literature to be epitopes for virus-induced cytotoxic T
      lymphocytes in asymptomatic HIV+ individuals. These observations, together with
      our results in multiple animal models and humans, establish that these conserved
      HIV envelope-derived peptides, particularly peptide 104, are significant T-cell
      epitopes with potential usefulness for induction of HIV-specific cell-mediated
      immune responses in humans.

PMID- 9918407
TI  - Infection of rabbits with R29 strain of bovine immunodeficiency virus: virulence,
      immunosuppression, and progressive mesenteric lymphadenopathy.
AB  - To assess the value of bovine immunodeficiency virus (BIV) infection as a model
      for human immunodeficiency virus (HIV) infection in man, we studied the
      impairment of certain immunologic functions in New Zealand white rabbits
      experimentally infected with an uncloned virulent isolate of the virus, BIV R29.
      Serum samples were tested by Western blot for the presence and persistence of
      antibody production. The T- and B-lymphocyte function was studied by evaluation
      of the blastogenic responsiveness to concanavalin A (Con A) and to dextran
      sulfate (DxS). All infected rabbits seroconverted to BIV antigens within 2 to 4
      weeks postinfection (p.i.) The BIV was isolated from the peripheral blood
      lymphocytes (PBLs) of 13 of 17 rabbits (77%) early in the infection and also from
      5 of 17 hyperplastic mesenteric lymph nodes (29%) and 10 of 17 spleens (59%)
      during the chronic stage of infection. Seven of 17 BIV-infected rabbits (41%)
      developed marked immunodepression 2 to 5 months p.i., and later, 5 exhibited a
      rapidly progressive disease with anorexia, weight loss, neurologic impairment,
      splenomegaly, and mesenteric lymphadenopathy. These data underline the value of
      the BIV model for studying HIV pathogenesis in vivo and the development of
      interventional strategies for AIDS.

PMID- 9918408
TI  - Inhibition of Ku autoantigen binding activity to the E2F motif after ultraviolet
      B irradiation of melanocytic cells.
AB  - In human melanocytes and a human melanoma cell line (MM96L), the level of Ku
      sequence-specific binding to a 37-mer oligonucleotide containing a single E2F-1
      binding site of the c-myc promoter (E2cM) significantly decreased 12 24h after
      cytostatic exposure to 300 J/m2 ultraviolet B radiation (UVB). No UVB-induced
      loss was found in fibroblasts, while HeLa cells showed an earlier (4 h) but less
      significant decrease than melanocytic cells. Equitoxic doses of gamma radiation,
      cisplatin or UVC had little effect on E2cM-specific binding. The loss of Ku
      binding in MM96L cells was not the result of translocation of Ku or a decrease in
      Ku protein or DNA-dependent protein kinase activity. The level of E2cM-specific
      binding in MM96L cells was increased by tunicamycin (2 microg/ml), an inhibitor
      of N-linked glycosylation, and decreased by the glucosidase inhibitor
      castanospermine (50 microg/ml). These results, which parallel the reported loss
      in melanocytes of the cell cycle regulator pRB after UVB, suggest that the DNA
      binding activity of Ku is affected by post-translational modification and may
      play a role in regulating the cell cycle response to UVB.

PMID- 9918409
TI  - Heterogeneous patterns of constitutive and heat shock induced expression of HLA
      linked HSP70-1 and HSP70-2 heat shock genes in human melanoma cell lines.
AB  - The heat shock response, which is characterized by the induction of heat shock
      proteins, is known to affect the ability of tumour cells to cope with potentially
      adverse conditions such as hypoxia, glucose starvation and cytotoxic immune
      reactions. To assess the heat shock response of melanoma cells, spontaneous and
      heat shock induced expression of heat shock proteins was analysed in a panel of
      17 human melanoma cell lines. Constitutive expression of HSP27, HSP70, HSC70,
      HSP90alphabeta and GRP94 proteins was found in all the melanoma cell lines, and
      HSP70 and HSC70 were also induced by heat shock. The major heat inducible HLA
      linked HSP70-1 and HSP70-2 genes were analysed at the mRNA level. Basal
      expression and inducibility varied between the different melanoma cell lines. In
      addition, in situ hybridization demonstrated heterogeneous expression of these
      genes among single cells of a given cell line. In general, each melanoma cell
      line appears to exhibit an individual type of HSP70 expression that might reflect
      selection during tumour progression and therapy.

PMID- 9918410
TI  - Tyrosinase transfection produces melanin synthesis and growth retardation in
      glioma cells.
AB  - Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We
      transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned
      in a high expression vector. Stable transfectants were selected by their
      resistance to the antibiotic G418. More than a dozen G418-resistant clones were
      isolated and were screened for tyrosinase expression using dopa-oxidase activity.
      The clone with the highest tyrosinase activity was selected and expanded for
      further studies. Northern blot analyses of total RNA from cells showed that the
      transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human
      melanotic melanoma cells. The melanin content of the transfected cells was
      dependent on the concentration of L-tyrosine in the culture medium. In addition,
      the growth of transfected cells was inhibited when grown in a medium containing
      high concentrations of L-tyrosine. These results suggest that tyrosinase activity
      is cytotoxic in a substrate-dependent manner. This may have far reaching
      therapeutic use for glioma tumours.

PMID- 9918412
TI  - Loss of expression or mutations in the p73 tumour suppressor gene are not
      involved in the pathogenesis of malignant melanomas.
AB  - Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and
      mapped to chromosome 1p36. Like p53, important functions of p73 in controlling
      the cell cycle and programmed cell death have been described. Loss of p73 has
      been demonstrated in neuroblastomas and its involvement in tumorigenesis has been
      suggested to occur in other neuroectodermal cancers. Since genetic alterations at
      the tumour suppressor locus 1p36 have been also identified in malignant
      melanomas, we investigated the expression of p73 in a panel of nine different
      human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas
      and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and
      Southern blotting. We observed significant p73 mRNA expression in all the cell
      lines and tissue specimens except one benign melanocytic naevus and one melanoma
      metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from
      primary tumours and five metastases over the entire p73 DNA binding domain
      revealed wild-type sequences in all cases. In summary, we conclude that loss of
      p73 mRNA expression or mutations in the p73 DNA binding domain do not represent
      common genetic events involved in the pathogenesis of malignant melanomas.

PMID- 9918411
TI  - Human acquired naevi are clonal.
AB  - Naevi are nearly universal in humans, yet their cellular origin remains obscure.
      Understanding the cellular and molecular mechanisms involved in naevus
      development may be important in understanding the pathogenesis of malignant
      melanoma. This study aimed to discover whether human acquired naevi are
      premalignant by examining whether they are clonal. To determine clonality naevi
      were removed and separated into epithelial and naevus cell fractions and the DNA
      prepared and digested by a methylase-sensitive restriction enzyme. The highly
      polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by
      a polymerase chain reaction and examined by gel electrophoresis and
      autoradiography. In polyclonal cell populations both alleles are usually seen as
      two distinct bands, whilst clonal populations yield a single band. Using these
      techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from
      40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal,
      while all of the epithelial cell controls were polyclonal. These data are novel
      and have great importance for understanding the development of human acquired
      naevi and cutaneous malignant melanoma. Because monoclonality is a marker of
      neoplasia, or preneoplasia, our data support the hypothesis that common acquired
      naevi should be considered to be premalignant lesions, similar to colonic polyps.
      Such lesions may have undergone the first molecular step(s) in the development of
      cutaneous malignant melanoma. Understanding the events involved may lead to new
      methods of prevention and treatment.

PMID- 9918413
TI  - Effect of radiation and tirapazamine (SR-4233) on three melanoma cell lines.
AB  - In this study the response of three melanoma cell lines to single doses of
      radiation, to the bioreductive drug tirapazamine (SR-4233) and to the combination
      of radiation and tirapazamine was determined. Tirapazamine is a bioreductive drug
      with specific cytotoxicity in hypoxic conditions. Three melanoma cell lines
      (MM576, MM96L and murine B16-F10) were exposed to increasing concentrations of
      tirapazamine to assess cytotoxicity under aerobic and hypoxic conditions. Also,
      clonogenic survival after single doses of 4 MV X-rays was determined under
      aerobic and hypoxic conditions, with and without 20 microM tirapazamine.
      Tirapazamine was an effective hypoxic cytotoxin in the three cell lines. The
      concentrations of tirapazamine causing equal cell kill were 1000 mM for aerobic
      cells and 50 mM for hypoxic cells. The oxygen enhancement ratios for single X-ray
      doses were between 2 and 3 for all the cell lines. Addition of 20 microM
      tirapazamine to hypoxic cells 1 h before irradiation produced the same
      radiosensitivity as aerobic cells. Tirapazamine had a minimal effect on the
      radiosensitivity of aerobic cells. Since melanomas are known to contain hypoxic
      cells which may reduce their radiosensitivity, these in vitro results have
      demonstrated the potential of tirapazamine to overcome the radioresistance of
      hypoxia and give encouragement for further studies.

PMID- 9918414
TI  - G2 accumulation and melanin overproduction in malignant melanocytes treated with
      a new nitrosourea.
AB  - Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a
      new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II
      clinical trial of disseminated melanoma. The antitumour effect of this drug is
      mainly due to DNA damage in malignant melanocytes. Recently, we have shown that
      this damage can induce apoptosis in some melanoma cell lines. In others,
      apoptosis is not clearly observed, although there is a strong cytostatic effect.
      In this paper, we have characterized the cytological effect of cystemustine on
      murine malignant melanocytes (B16 cell line) which are resistant to apoptosis
      induced by this CENU. The results show that 3 days after cystemustine treatment,
      these melanocytes had accumulated in phase G2 of the cell cycle. There was then a
      strong morphological modification during a long cytostatic phase up to 30 days
      after treatment. During this cytostatic phase, there was uncontrolled DNA
      synthesis and marked swelling. Also, tyrosinase activity, melanin content and the
      number of mature melanosomes were greatly increased. These results suggest that
      when malignant melanocytes are not able to undergo apoptosis after treatment with
      CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.

PMID- 9918415
TI  - Epiluminescence microscopy as a useful approach in the early diagnosis of
      cutaneous malignant melanoma.
AB  - The aim of this study was to evaluate the role of epiluminescence microscopy
      (ELM) in the differential diagnosis of cutaneous pigmented lesions in order to
      improve the detection of cutaneous malignant melanoma (CMM) at earlier stages of
      the disease. In total, 3865 pigmented lesions from 2121 selected patients were
      evaluated using ELM with a hand-held video microscope imaging system (MS 500B
      Micro-Scopeman, Moritex). Comparison with histology was performed on the 476
      surgically excised lesions. ELM sensitivity, specificity, positive and negative
      predictive values as well as agreement for the different risk levels of the
      lesions were determined. Of the 476 cutaneous pigmented lesions removed and
      histologically examined, 101 (21.2%) were non-melanocytic lesions and 375 (78.8%)
      were melanocytic lesions. Overall agreement was 83.4% (93.1% and 80.8% for non
      melanocytic and melanocytic lesions, respectively). Sensitivity and specificity
      of ELM in the analysis of melanocytic lesions with a pigment network were both
      very high (92.3% and 91.2%, respectively). Sixty new cases of CMM were
      identified. A high proportion of melanoma at stage AJCC IA (23 out of 32; 71.8%)
      was diagnosed exclusively by ELM (four of these were in situ CCM lesions). ELM is
      therefore a powerful tool to discriminate between melanocytic and non-melanocytic
      lesions in order to avoid inopportune surgical treatments for low risk lesions.
      Unfortunately, ELM did not show 100% sensitivity in diagnosing CMM and therefore
      ELM features should be integrated with data from both the history and clinical
      evaluation. However, ELM is much more accurate than clinical examination in
      detecting thin CMM.

PMID- 9918416
TI  - Effect of topical tretinoin under occlusion on atypical naevi.
AB  - Atypical naevi are potential precursors of melanoma and markers of increased
      melanoma risk. To examine the possibility of chemoprevention of melanoma by
      retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic
      acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi.
      Thirty patients with atypical naevi were enrolled in a prospective randomized
      double blind study. For each patient three comparable naevi were selected and
      randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1%
      (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months.
      Baseline views of the naevi, taken with a videomicroscope (magnification 20 x),
      were assessed for morphological changes compared with views taken 2 months after
      the beginning of treatment, 1 week after completion of treatment and 6 months
      later. After completion of the study all naevi in the T and C groups and six
      naevi in the P group were removed and evaluated histologically for the presence
      of atypia. The number of naevi that had changed in colour or size was
      significantly higher in the T and C groups compared with the placebo group. A
      size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour
      changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle,
      did not differ significantly between groups T and C, but naevi treated with C
      became significantly less irritated. Histologically, 75.0% of the naevi treated
      with T and 69.6% of the naevi treated with C were atypical. Therefore, no major
      change was seen in the clinical aspect of atypical naevi after treatment with
      tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi
      still met the histological criteria for atypia after the treatment period. The
      current management of follow-up of atypical naevi and excision when change to
      melanoma is suspected is therefore still recommended. Nevertheless, some response
      was seen, which may justify a further exploration of tretinoin and hydrocortisone
      1% therapy for a longer treatment period in combination with research to clarify
      its mechanism.

PMID- 9918417
TI  - Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients
      with local-regional metastases.
AB  - Our results with concurrent biochemotherapy in patients with stage IV melanoma
      have been encouraging. Based on these data, we conducted a phase II study to
      determine the clinical and histological response rate to neoadjuvant concurrent
      biochemotherapy in patients with local-regional metastases of cutaneous melanoma
      (stage III). A total of 65 patients with biopsy-proven, measurable and
      potentially resectable local-regional disease (nodal, satellite/in-transit
      metastases and/or local recurrence) were treated with cisplatin 20 mg/m2
      intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4,
      dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by
      96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2
      subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery
      after two to four courses of biochemotherapy. Those with tumour regression after
      two preoperative courses received two additional postoperative courses. Of the 64
      patients assessable for clinical response, 28 (44%) had a partial response. Of
      the 62 patients whose response was assessed histologically, four (6.5%) had no
      evidence of viable tumour in the surgical specimen (pathological complete
      remission, pCR) and 27 (43.5%) had a partial response, giving an overall response
      rate of 50%. Tumour burden did not correlate with response, although patients who
      achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II
      study indicates that neoadjuvant biochemotherapy is an active treatment for
      melanoma patients with local-regional metastases. However, it is unclear if
      biochemotherapy is more active than chemotherapy alone; phase III randomized
      trials are ongoing to answer this question in patients with stage IV disease.

PMID- 9918418
TI  - Long-term outcome of treatment with dacarbazine, cisplatin, interferon-alpha and
      intravenous high dose interleukin-2 in poor risk melanoma patients.
AB  - Melanoma patients with very advanced disease are usually excluded from
      chemoimmunotherapy trials; however, the efficacy of intensive treatment regimens
      needs to be established for this patient population. This study aimed to evaluate
      the response rate and survival achieved with chemoimmunotherapy in very advanced
      melanoma patients. Forty-two patients received dacarbazine (250 mg/m2, days 1-3),
      cisplatin (30mg/m2, days 1-3), interferon-alpha (10 Mio IU/m2 subcutaneously,
      days 1-5) and intravenous interleukin-2 (18 Mio IU/m2 over 6 h, 12 h then 24 h,
      followed by 13.5 MioIU/m2 in 72 h). In cases of brain metastases (n = 12)
      radiation therapy was added. Ten patients (24%) achieved a partial response, 11
      (26%) had stable disease and 21 (50%) had disease progression in an intention-to
      treat analysis. The median overall survival of patients with a partial response
      or stable disease was 9 months in contrast to 3.5 months in patients with disease
      progression. Normal serum lactate dehydrogenase before the start of treatment was
      a strong favourable prognostic marker for survival (P< 0.002). We conclude that
      the described treatment schedule offers safe palliation in patients with very
      advanced metastatic melanoma.

PMID- 9918419
TI  - Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients
      with metastatic malignant melanoma.
AB  - Inspired by the high response rates achieved with the DBCT regimen (dacarbazine
      [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the
      nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients
      with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were
      administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the
      second course onwards. Pharmacokinetic blood sampling was performed in 14
      patients during the initial two cycles to compare the pharmacokinetic behaviour
      of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed,
      and patients with brain metastases or concomitant other malignancies were
      included. Four complete and 11 partial responders were observed among 66
      evaluable patients, yielding a response rate of 22.7% (95% confidence interval
      12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The
      main toxicities were thrombocytopenia, protracted nausea/vomiting and
      ototoxicity. Renal toxicity was generally mild, but possibly contributed to two
      deaths. Seven patients experienced deep venous thrombosis during the study. TAM
      had no influence on the pharmacokinetics of fotemustine. The activity of the FCT
      regimen was clearly inferior to that initially reported with DBCT treatment.
      However, a recent publication concludes that the latter achieves a considerably
      lower response rate when administered to a larger patient group. We believe our
      results reflect the true activity of FCT and similar regimens when administered
      routinely to unselected patients. Considering the number of potentially serious
      side effects, we cannot recommend the moderately active FCT regimen as a
      palliative treatment option for melanoma patients.

PMID- 9918420
TI  - Parallel risk assessment of melanoma and basal cell carcinoma: skin
      characteristics and sun exposure.
AB  - In this study we compared the strength of the association of constitutional
      factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell
      carcinoma (BCC). We analysed 260 incident cases of CMM, 425 incident cases of BCC
      and two sets of population controls from previous case-control studies conducted
      in Turin, Italy. Simultaneous comparison was accomplished by comparing separate
      simple logistic and polytomous logistic regressions. Tendency to sunburn was
      shown to be the most important risk indicator for both types of tumours, being
      associated with a two- to three-fold increase in risk for CMM and a two-fold
      increase in risk for BCC. Intermittent and intense sun exposure, as during beach
      holidays, increased the risk of both CMM and BCC, while prolonged exposure to
      sun, as during outdoor occupations, was not associated with CMM or BCC. The
      increase in risk during beach holidays occurred mainly during childhood for CMM
      cases, while for BCC cases it also continued during adulthood. Analysis of the
      independent effect of risk factors confirmed the role of skin phenotype (eye
      colour odds ratio [OR] = 1.6, tendency to sunburn OR = 2.1) and intermittent sun
      exposure (sunburns in childhood OR = 3.8, sun exposure during beach holidays OR =
      1.2) in CMM. Risk of CMM showed a significant increase when sun exposure exceeded
      the threshold of about 3500 h during beach holidays cumulated in a lifetime. In
      contrast, the role of skin phenotype in BCC is less strong, but cumulated hours
      of sun exposure during beach holidays in a lifetime showed a constant risk rise
      with an early plateau at a low exposure level.

PMID- 9918421
TI  - Cytokines as predictors of severity in acute pancreatitis.

PMID- 9918422
TI  - Endoscopic management of choledocholithiasis: to cut, stretch or relax?
AB  - Since it was first described in 1974, endoscopic sphincterotomy has been the
      procedure of choice for management of choledocholithiasis, especially for
      retained common bile duct stones. However, it has the dubious distinction of
      being the most hazardous of all endoscopic retrograde cholangiopancreatographic
      procedures and carries an immediate complication rate of 8-10%. Concern has also
      been voiced about the long-term complications of sphincterotomy, as the sphincter
      of Oddi is cut during the procedure. To prevent, or at least lessen, the short-
      and long-term complications of endoscopic sphincterotomy, an alternative in the
      form of balloon dilatation of the papilla, has been advocated. However, the
      procedure of balloon dilatation is cumbersome, time consuming and, more
      importantly, a recent multi-centre study from the US comparing endoscopic
      sphincterotomy with balloon dilatation observed higher complications with balloon
      dilatation. The use of nitrites to relax the papilla is another novel method used
      for removal of common bile duct calculi. So how should a therapeutic endoscopist
      decide which method is to be used? The advantage of endoscopic sphincterotomy is
      that it has been around for more than two decades and most endoscopists are
      familiar with the technique as well as its complications. It can be accomplished
      quickly and with the advent of wire-guided and balloon-mounted sphincterotomes,
      the time taken for the procedure to be completed has been reduced further. The
      complications of the procedure are less when it is employed for removal of common
      bile duct stones and when used by experts. It, therefore, still appears to be the
      procedure of choice for endoscopic management of choledocholithiasis. The other
      two methods may, however, be useful in patients with coagulopathy.

PMID- 9918423
TI  - Modulation of intestinal immune system by dietary fat intake: relevance to
      Crohn's disease.
AB  - Gut-associated lymphoid tissue is the major inductive site of the mucosal immune
      system, which is functionally independent of the systemic immune system. Both the
      amount and type of dietary fat modulate intestinal immune function. Absorption of
      long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in
      intestinal lymphatics. Long-chain fatty acid absorption also significantly
      enhances migration of T lymphocytes to Peyer's patches, possibly due to up
      regulation of adhesion molecules, such as alpha4-integrin and L-selectin.
      Lipoproteins are involved in stimulation of lymphocyte function by both receptor
      dependent and independent mechanisms. However, unsaturated fatty acids at higher
      concentrations have a suppressive effect on cell-mediated immunity via eicosanoid
      release, receptor affinity changes or interactions with intracellular signal
      transduction. Fat absorption also influences various other cells in the
      intestinal mucosa: increased cytokine release from intestinal epithelial cells
      follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and
      total parenteral nutrition often induce remission, possibly by reducing antigenic
      load on activated immune cells in the intestine and, thus, down-regulating
      hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological
      reversal effect in the intestinal immune system of animals fed an elemental diet.
      An excess of long-chain fatty acids in an elemental diet, therefore, may negate
      its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In
      contrast, supplemental dietary fish oil apparently tends to prevent relapse of
      Crohn's disease. Because dietary fat intake is closely associated with
      immunological function of the intestinal mucosa, careful manipulation of dietary
      fat can be important in management of this disease.

PMID- 9918424
TI  - Helicobacter pylori-induced lymphonodular hyperplasia: a new cause of gastric
      outlet obstruction.
AB  - A 30-year-old female was seen with symptoms and radiological evidence of gastric
      outlet obstruction. Endoscopic examination revealed findings suggestive of
      gastric outlet obstruction with nodularity of the antral mucosa leading to
      deformity of the pylorus. Endoscopic biopsies from the nodular antral mucosa
      showed presence of Helicobacter pylori-induced lymphonodular hyperplasia without
      evidence of mucosa-associated lymphoid tissue lymphoma. Anti-H. pylori therapy
      resulted in eradication of the H. pylori infection and the signs and symptoms of
      gastric outlet obstruction. The case demonstrates that H. pylori-induced
      lymphonodular hyperplasia can also cause gastric outlet obstruction. We believe
      this is the first such case to be reported.

PMID- 9918425
TI  - Sulindac inhibits colorectal tumour growth, but not prostaglandin synthesis in
      the rat.
AB  - We have determined the dose-response relationship between sulindac administration
      and inhibition of tumour growth in the rat. The effect of tumour-inhibiting doses
      of sulindac on the production of prostaglandin E in tumours and macroscopically
      normal colon was then examined. Growth of pre-existing tumours was significantly
      reduced following administration of sulindac at 0.1 (P=0.004), 1 (P=0.01), 3
      (P<0.001) and 10 mg/kg b.d. (P=0.002) for 4 weeks. There was no significant
      difference in prostaglandin E synthesis between tumours from control rats and
      those treated with sulindac at either 3 or 10 mg/kg b.d. (P=0.09 and 0.4,
      respectively). Prostaglandin E synthesis was reduced by 33 and 32% in
      macroscopically normal tissue from these treatment groups. These data show that
      sulindac inhibits tumour growth at low doses and do not support a role for the
      inhibition of prostaglandin synthesis, by sulindac, in the inhibition of tumour
      growth.

PMID- 9918426
TI  - Long-term effect of alpha-glucosidase inhibitor on late dumping syndrome.
AB  - Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is
      one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an
      excessive insulin secretion after a sharp rise in plasma glucose. Several
      treatments, including operation, dietary fibre and somatostatin, have been
      attempted to relieve dumping symptoms. These treatments take effect through
      modulation of plasma insulin and glucose levels, but their efficacy is still
      under consideration. Alpha-glucosidase inhibitor attenuates the postprandial
      increase of plasma glucose levels and is widely used for treatment of non-insulin
      dependent diabetes mellitus (NIDDM). The acute effect of alpha-glucosidase
      inhibitor on late dumping syndrome has been reported by some studies with test
      meals. The purpose of this study was to evaluate a long-term effect of alpha
      glucosidase inhibitor treatment with ordinary meals in late dumping patients with
      NIDDM because administration of alpha-glucosidase inhibitor is only ethically
      allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were
      orally administered alpha-glucosidase inhibitor, acarbose (50 or 100 mg), three
      times a day before each meal for 1 month. Diurnal changes of plasma glucose,
      insulin and pancreatic glucagon levels were compared before and after the alpha
      glucosidase inhibitor treatment. All patients had late dumping-related symptoms,
      such as weakness, palpitation and dizziness before the induction of alpha
      glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma
      glucose levels from hyperglycaemia at the same time as dumping symptoms. These
      late dumping-related symptoms disappeared and a rapid change of plasma glucose
      and insulin levels were attenuated after the alpha-glucosidase inhibitor
      treatment. These data suggest a long-term therapeutic efficacy of alpha
      glucosidase inhibitor for late dumping patients.

PMID- 9918427
TI  - Immunoproliferative small intestinal disease in South India: a clinical and
      immunomorphological study.
AB  - Immunoproliferative small intestinal disease (IPSID), a proliferative disorder
      affecting the intestinal immune system, has only been reported sporadically in
      India. Fifteen patients with malabsorption syndrome who were diagnosed to have
      IPSID were included in this study. Mucosal biopsies from all patients, full
      thickness surgical biopsies from 10 and autopsy material from four patients were
      examined by light microscopy and immunohistochemistry. The patients were
      predominantly young (aged 16-36 years) and male (13 of 15). Diarrhoea, weight
      loss, vomiting and abdominal pain were the major symptoms. The upper small bowel
      was involved in all cases. Involvement of large bowel was detected antemortem in
      three patients, but was found in all autopsied patients. Involvement of the
      stomach was noted in one patient at autopsy. Mesenteric lymph nodes were involved
      in all patients who underwent laparotomy. The plasmacytic infiltrate was
      uniformly positive for alpha-heavy chain, and either negative for light chain
      production or showed monotypic light chain production. Some of the blasts were
      also positive for alpha-heavy chain. Three patients died before therapy could be
      commenced. One patient with stage A disease is alive and clinically free of
      disease at 7 years. Of the remainder, there have been four long-term survivors
      with chemotherapy. Immunoproliferative small intestinal disease occurs in
      southern India and has characteristics similar to that in other parts of the
      world. Early diagnosis may improve outcome in this disease.

PMID- 9918428
TI  - Bile acids inhibit tumour necrosis factor alpha-induced interleukin-8 production
      in human colon epithelial cells.
AB  - To clarify the regulatory mechanism of the production of various inflammatory
      mediators by intestinal epithelial cells, the effect of bile acids
      (tauroursodeoxycholate, TUDC; taurochenodeoxycholate, TCDC; and taurocholate, TC)
      on the cytokine-induced production of interleukin (IL)-8 in a human colon
      epithelial cell line (HT-29) was examined. HT-29 cells were incubated for 24 h in
      a culture medium containing tumour necrosis factor alpha (TNF alpha; 1 ng/mL)
      and/or interleukin (IL)-1beta (1 ng/mL) in the presence or absence of bile acids.
      The IL-8 concentration in the medium was measured by an enzyme-linked
      immunosorbent assay. The binding assay of TNF alpha was performed using [125I]
      TNF alpha (100 pmol/L). Interleukin-8 production during incubation with TNF alpha
      was markedly reduced in the presence of 0.5 and 1 mmol/LTUDC, 0.5 and 1
      mmol/LTCDC and 0.5 and 1 mmol/LTC, by 56, 85, 86, 91, 37 and 70%, respectively.
      The IL-8 production during incubation with IL-1beta was not significantly reduced
      in the presence of these bile acids. The specific binding of TNF alpha to cells
      was inhibited 33, 47, and 14% by 1 mmol/LTUDC, TCDC and TC, respectively. These
      findings suggest that bile acids inhibit TNF alpha-induced IL-8 production by the
      colonic cells. The suppression may be partly due to inhibition of TNF alpha
      binding to the cells by bile acids.

PMID- 9918429
TI  - Effects of eating on plasma hyaluronan in patients with cirrhosis: its mechanism
      and influence on clinical interpretation.
AB  - Circulating levels of hyaluronan (HA) may be a clinically useful non-invasive
      test in liver disease to evaluate, for example, the degree of fibrosis or
      cirrhosis. Healthy subjects exhibit a two-fold or greater postprandial elevation
      of plasma HA. We undertook this work to determine the effect of eating on plasma
      HA in patients with cirrhosis, to define mechanisms underlying the changes
      observed and to examine whether using fasting samples improves the discriminating
      value of plasma HA as a clinical test. Plasma HA was measured using a protein
      binding assay in serial samples obtained over 2.5 h, during which a 2100 kJ meal
      and/or intravenous infusion of octreotide (25 microg stat, 25 microg/h) were
      given, or in paired random and fasting samples from patients with cirrhosis. In
      six patients with Pugh's A cirrhosis, plasma HA increased more than two-fold
      after food ingestion, peaking after 75-90 min. In four patients (one Pugh's A),
      no response was observed. Octreotide transiently increased plasma HA by a mean of
      20%, but, in combination with eating, reduced the peak plasma HA by 80% in
      responding patients. In 30 patients with cirrhosis, random plasma HA was abnormal
      in only 70% compared with 93% of autologous fasting samples, using the respective
      normal ranges (P=0.01). Ingestion of food markedly increased plasma HA in
      patients with compensated but not decompensated cirrhosis, most likely due to a
      postprandial increase in splanchnic blood flow. Fasting patients prior to taking
      blood improves the clinical discriminating value of plasma HA.

PMID- 9918430
TI  - Coexistence of proguanylin (1-15) and somatostatin in the gastrointestinal tract.
AB  - In order to identify proguanylin-secreting cells, we have raised an antiserum
      against the synthetic fragment of human proguanylin (1-15) and have examined the
      proguanylin-positive cells in the human and rat gastrointestinal tract by
      immunohistochemical methods. Numerous proguanylin (1-15)-immunoreactive cells
      were found in the gastrointestinal tract. They were either pyramidal or spindle
      shaped in the stomach. Spindle-shaped cells, frequently possessing long slender
      processes, were located at the base of the pyloric epithelium and did not extend
      to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in
      shape and often had a slender process towards the lumen. The immunostaining was
      completely blocked by the human proguanylin (1-15) fragment. Paneth and goblet
      cells were negative against this antiserum. The number of serotonin-positive
      cells was much larger than that of proguanylin-positive cells in all the segments
      tested. The number of proguanylin-positive cells decreased from the jejunum to
      the ileum and very few cells were observed in the colon. In contrast to serotonin
      positive cells, most somatostatin-positive cells were also positive for
      proguanylin. Thus, proguanylin (1-15) or its related protein appears to coexist
      with somatostatin in intestinal endocrine D cells which may be a source of
      circulating proguanylin. Proguanylin, like somatostatin, may also regulate
      intestinal function as a local regulator.

PMID- 9918431
TI  - Idiopathic localized dilatation of the ileum. A rare cause of gastrointestinal
      haemorrhage in an adult.
AB  - A case of idiopathic localized dilatation of the ileum presenting in adulthood
      and associated with small bowel malrotation, ulceration and bleeding is
      described. To our knowledge, this is the first such report of this combination of
      features. The diagnosis was made using a small bowel barium study and intra
      operative enteroscopy. Idiopathic localized dilatation of the ileum with
      ulceration should be considered as a rare small intestinal cause of occult or
      frank gastrointestinal blood loss in children or young adults.

PMID- 9918432
TI  - Significance of the minor i and t determinants of hepatitis B virus in
      hepatocellular carcinoma.
AB  - Stored sera from asymptomatic hepatitis B virus (HBV) carriers and hepatitis B
      virus surface antigen-positive hepatocellular carcinoma (HCC) patients were
      tested for HBV subtypes, such as subtype determinants d, y, w, r and also
      antigenic determinants isoleucine (i) and threonine (t) by direct S gene
      nucleotide sequencing. Significant changes in minor i and t determinants in
      hepatocellular carcinoma patients with adr hepatitis B carriers were seen. The
      adr subtype with t determinant was present in 14/25 (56%) of HCC patients
      compared with only two of 28 (7%) in asymptomatic hepatitis B carriers (P<0.001).
      However, the adr subtype with i determinant was present in nine of 25 (36%) of
      the HCC patients and also present in 24/28 (86%) of asymptomatic carriers
      (P<0.001). No significant changes were seen with the adw subtypes. These results
      show that i and t minor determinant changes are more common with adr subtypes
      associated with HCC than with the adw subtype. Whether these subtle changes are
      pathologically relevant or only a polymorphism of hepatitis B genotypes will
      depend on subsequent follow-up studies.

PMID- 9918433
TI  - GB virus C/hepatitis G virus infection among patients with hepatocellular
      carcinoma in the inshore area of the Yangtze River, China.
AB  - To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV)
      infection and the development of hepatocellular carcinoma (HCC) in H city, in the
      inshore area of the Yangtze River, where high prevalence of HCC has been
      reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV)
      markers, GBV-C/HGV-RNA and GBV-C/HGV E2 antibody (anti-HG E2) among 114 HCC
      patients and the same number of age- and sex-matched controls. There were no
      significant differences in the clinical and demographic characteristics between
      them, except for serum alanine aminotransferase level and history of liver
      diseases. There was a significant difference of hepatitis B virus surface antigen
      (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%;
      P<0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients,
      compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E2 were
      detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0
      and 1.7% of the controls, respectively. Nucleotide sequences and molecular
      evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into
      genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR)
      for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was
      14.9, with a 95% CI of 4.9-45.4. HBsAg infection alone was 13.83 (95% CI 7.4
      25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1-13.1), respectively. These
      data indicate that HBV infection is considered to be one of the major risk
      factors in patients with HCC and although GBV-C/HGV infection was observed in
      both the HCC and the control groups, it might not play an important role in the
      development of HCC in this area.

PMID- 9918434
TI  - Efficacy of ribavirin plus interferon alpha on viraemia of GB virus-C/hepatitis G
      virus: comparison with interferon alpha alone.
AB  - We investigated the efficacy of ribavirin plus interferon (IFN) alpha on GB virus
      C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of
      interferon alpha alone in patients coinfected with hepatitis C virus (HCV) and
      GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV
      and GBV-C/HGV coinfection, five received IFN alpha and three received oral
      ribavirin plus IFN alpha. Mean serum GBV-C/HGV titre at the end of therapy was
      significantly lower than the titre just before therapy and patients with lower
      pretreatment titre had a better sustained response rate. Sustained virological
      response of GBV-C/HGV to IFN alpha alone and ribavirin plus IFN alpha at the end
      of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients
      with HCV and GBV-C/HGV coinfection does respond to IFN alpha and ribavirin plus
      IFN alpha may not induce a higher sustained response.

PMID- 9918435
TI  - In vitro and in vivo vascular responses to the L-type calcium channel activator,
      Bay K 8644, in rats with cirrhosis.
AB  - A substance which increases the entry of extracellular calcium into arterial
      smooth muscle may decrease cirrhosis-induced vasodilation. The aim of the present
      study was to measure the effects of the L-type Ca2+ channel activator, Bay K
      8644, on the haemodynamics of rats with cirrhosis. Vascular reactivity to this
      substance was also investigated. Splanchnic and systemic haemodynamic responses
      to Bay K 8644 (50 microg/kg) were measured in cirrhotic and normal rats.
      Contraction induced by 0.1 micromol/L Bay K 8644 was measured in arterial rings
      (aorta and superior mesenteric artery) from cirrhotic and normal rats. In
      cirrhotic rats, Bay K 8644 significantly decreased portal pressure (15%) and
      portal tributary blood flow (24%), significantly increased portal territory
      vascular resistance (54%) and did not significantly change hepatocollateral
      vascular resistance. Bay K 8644 significantly increased arterial pressure (7%)
      and systemic vascular resistance (24%) and did not change the cardiac index. In
      normal rats, Bay K 8644 significantly increased vascular resistance (150%) in
      portal, hepatocollateral and systemic territories and significantly decreased the
      cardiac index (44%). Changes in portal territory, hepatocollateral and systemic
      vascular resistances were significantly less marked in cirrhotic than in normal
      rats. In rings from the aorta and superior mesenteric artery, Bay K 8644-induced
      contraction was significantly lower in cirrhotic than in normal rats. In
      conclusion, in rats with cirrhosis, Bay K 8644 administration reduced
      vasodilation in splanchnic and systemic arteries and did not affect
      hepatocollateral vascular resistance. The Bay K 8644-induced reduction in
      splanchnic vasodilation caused a decrease in portal hypertension. This study also
      shows that Bay K 8644-induced vascular contraction was less marked in cirrhotic
      than in normal rats, in systemic and splanchnic vascular beds.

PMID- 9918436
TI  - Treatment of cirrhotic rats with epidermal growth factor and insulin accelerates
      liver DNA synthesis after partial hepatectomy.
AB  - Prevention of postoperative hepatic failure is important after hepatic resection.
      In patients with cirrhosis, impaired liver function and regenerative capacity
      after major hepatic resection are associated with increased morbidity and
      mortality. In this study, a combination of epidermal growth factor (EGF) and
      insulin were used as hepatotrophic factors in an attempt to stimulate DNA
      synthesis after 70% hepatectomy (HTX). Regenerative capacity was evaluated in
      normal and cirrhotic rat liver by measuring DNA synthesis in vivo. Micronodular
      liver cirrhosis was established by the simultaneous oral administration of CCl4
      and phenobarbital. Epidermal growth factor plus insulin was injected
      subcutaneously immediately after and 12 h after HTX or sham operation was
      performed. Rats were killed 24 h after the operation and liver regeneration was
      estimated by [3H]-thymidine incorporation into DNA as well as an autoradiographic
      nuclear labelling index. Hepatectomy increased [3H]-thymidine incorporation
      significantly in both normal and cirrhotic rats. In cirrhotic rats, [3H]
      thymidine incorporation after HTX was significantly lower than in normal rats and
      administration of a combination of EGF and insulin after HTX enhanced [3H]
      thymidine incorporation. In conclusion, DNA synthesis 24 h after HTX is decreased
      in cirrhotic rats compared with normal rats and EGF supplementation with insulin
      accelerates DNA synthesis in hepatectomized cirrhotic rats. The data suggest that
      administration of combinations of exogenous hepatotrophic factors may play a
      useful role in the treatment of cirrhotic patients undergoing major hepatic
      resection.

PMID- 9918437
TI  - Relationship of angiographic finding with neovascular structure detected by
      immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular
      carcinoma.
AB  - To elucidate the relationship between angiographic features and histological
      findings, an immunohistological study of alpha-smooth muscle actin was performed
      in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal
      blood paucity were found in 73 patients (68.9%) on digital subtraction
      angiography, 88 (83.0%) on computerized tomographic arterial portography and 87
      (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with
      hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich and
      slender-shaped vessels (type II), eight (11.0%) had thin-walled, nuclei-poor and
      oval-shaped vessels (type I) and the remaining eight had a mixed type of II and
      I. Conversely, among 33 patients without hypervascularity, five (15.2%) had a
      type II, 21 (63.6%) had a type I, five had a mixed type and two had no positive
      vessel. Tumour size, histological classification and amount of non-triadal
      vessels were also associated with the angiographic appearance of the tumours.
      Among varied aspects of the cancer including tumour size, tumour multiplicity,
      microscopic portal invasion, histological classification, amount of alpha-smooth
      muscle actin-positive vessels and shape of alpha-smooth muscle actin-positive
      vessels, multivariate logistic regression analysis demonstrated that the shape of
      alpha-smooth muscle actin-positive vessels was solely associated with
      angiographic hypervascularity independently (P<0.0001). Although the existence of
      non-triadal vessels characterized hepatocellular carcinoma, angiographic
      hypervascularity was closely associated with the type II vessel. A morphological
      change of non-triadal vessel from type I to type II was considered to occur in an
      early stage of hepatocellular carcinoma.

PMID- 9918440
TI  - Hepatobiliary and pancreatic: patient: magnetic resonance imaging in gall-bladder
      pathology.

PMID- 9918438
TI  - Blood concentrations of polymorphonuclear leucocyte elastase and interleukin-6
      are indicators for the occurrence of multiple organ failures at the early stage
      of acute pancreatitis.
AB  - We studied potential indicators of severe acute pancreatitis by measuring the
      blood concentrations of various cytokines, polymorphonuclear leucocyte elastase
      (PMN-E), acute phase reactants, pancreatic amylase (P-AMY), pancreatic elastase-1
      (E-1) and white blood cell (WBC) counts in patients with acute pancreatitis. In
      addition, the presence of multiple organ damage was assessed. Subjects consisted
      of 22 patients with acute pancreatitis including severe (n = 11), moderate (n =
      4) and mild (n = 7) cases. A significant positive correlation was observed
      between the number of organs damaged and the peak concentrations of interleukin
      (IL)-6, PMN-E, C-reactive protein (CRP) and pancreatic secretory trypsin
      inhibitor (PSTI). Among these markers, blood concentrations of PMN-E and IL-6
      rapidly increased and peaked at the early phase of acute pancreatitis whereas CRP
      and PSTI did not. The elevation of PMN-E and IL-6 was greater the more severe the
      symptoms. However, no significant correlation was observed between the number of
      organs damaged and the maximum serum concentrations of P-AMY and E-1, or the WBC
      count, which have been considered to be markers of pancreatitis. These results
      suggest that PMN-E and IL-6 concentrations are useful indicators of severity and
      prognosis and their determination facilitates the selection of appropriate
      treatment in the early stages of disease to prevent the aggressive progression of
      acute pancreatitis.

PMID- 9918439
TI  - Gastrointestinal: herpes simplex oesophagitis.

PMID- 9918441
TI  - Do not resuscitate orders and stopping resuscitation.

PMID- 9918442
TI  - Decisions to terminate resuscitation. Resuscitation Committee.
AB  - To gain more insight into decision making around the termination of resuscitation
      (CPR), we studied factors which influenced the time before discontinuing
      resuscitation, and the criteria on which those decisions were based. These
      criteria were compared with those of the European Resuscitation Council (ERC) and
      the American Heart Association (AHA). For this study, we reviewed the audiotapes
      of resuscitation attempts in a hospital. A total of 36 attempts were studied,
      involving 27 men and nine women, mean (S.D.) age 64 (18) years. A total of 19
      patients received resuscitation on general wards, and 17 in the emergency room
      after an out-of-hospital circulatory arrest. The median interval time (range)
      from start to termination was 33 min (8-81 min). Results from multiple linear
      regression showed that a delay greater than 5 min in first advanced life support
      measures, drawing a sample for biochemical analysis, and the patient's response
      shown by return of spontaneous circulation were independently associated with the
      time of terminating resuscitation. The team used a number of criteria which can
      be found in the guidelines of the ERC and the AHA, but also used additional
      criteria. The ERC and the AHA criteria were not sufficient to cover all
      termination decisions. We conclude that the point in time to terminate
      resuscitation is not always rationally chosen. Updating of the current guidelines
      for terminating resuscitation and training resuscitation teams to use these
      guidelines is recommended.

PMID- 9918443
TI  - Impact of survival probability, life expectancy, quality of life and patient
      preferences on do-not-attempt-resuscitation orders in a hospital. Resuscitation
      Committee.
AB  - Consensus exists that a do-not-attempt-resuscitation order (DNAR) is appropriate
      if a resuscitation attempt is futile. Less agreement exists when this point is
      reached. We investigated the influence of three major considerations for in
      hospital DNAR orders: expected survival probability after resuscitation,
      prospects of the patients' current condition without a cardiac arrest and the
      patients' autonomous decision not to want resuscitation. We calculated an
      expected survival probability according to two multi-morbidity prediction scores
      for each patient, assuming the event of cardiac arrest. The prospects of the
      current condition without a cardiac arrest was estimated by the patients'
      physician, in terms of life expectancy and quality of life (level of dependency
      after discharge and pain). The patients' preference was documented from the
      medical records. A total of 470 patients were included in the study. Fifty-eight
      patients (12%) had a DNAR-order, 11 of these patients (19%) wanted no
      resuscitation. The patients' prospects (life expectancy, dependency after
      discharge), and age proved to be independently associated with the presence of a
      DNAR order. The odds ratio (OR) for the presence of a DNAR order was 37 (CL 14
      107) for an estimated life expectancy less than 3 months, 13 (CL 4-41) for a life
      in a nursing home and four (CL 2-12) for an age of 80 years and older. Expected
      survival probability after resuscitation and pain were not independently
      associated with a DNAR order. We conclude that resuscitation is considered futile
      on the basis of the patients' age and prospects without cardiac arrest and that
      the impact of expected survival probability on these decisions is small.

PMID- 9918445
TI  - Intravenous amiodarone for ventricular arrhythmias: overview and clinical use.
AB  - Numerous pharmacological agents with varying cellular electrophysiological
      effects are available to treat cardiac arrhythmias. Amiodarone is predominantly a
      Vaughan Williams Class III agent, but also possesses electrophysiological
      characteristics of the other three Vaughan Williams classes (Class I and IV and
      minor Class II effects). Amiodarone's primary mechanism is to prolong the cardiac
      action potential and repolarization time leading to an increased refractory
      period and reduced membrane excitability. The efficacy and tolerability of
      intravenous (IV) amiodarone for acute treatment of recurrent and refractory
      ventricular tachycardia and ventricular fibrillation has been demonstrated in
      clinical trials. The ARREST trial, a randomized trial comparing IV amiodarone to
      placebo, found a significant improvement in the proportion of patients surviving
      to the emergency department following out-of-hospital cardiac arrest in
      amiodarone-treated patients. Intravenous amiodarone is an effective anti
      arrhythmic agent for the acute treatment of life-threatening ventricular
      arrhythmias and represents an important treatment option for emergency anti
      arrhythmic therapy for patients suffering from cardiac arrest.

PMID- 9918444
TI  - Characteristics and outcome among patients with a suspected in-hospital cardiac
      arrest.
AB  - AIM: To describe the characteristics and outcome among patients with a suspected
      in-hospital cardiac arrest. METHODS: All the patients who suffered from a
      suspected in-hospital cardiac arrest during a 14-months period, where the
      cardiopulmonary resuscitation (CPR) team was called, were recorded and described
      prospectively in terms of characteristics and outcome. RESULTS: There were 278
      calls for the CPR team. Of these, 216 suffered a true cardiac arrest, 16 a
      respiratory arrest and 46 neither. The percentage of patients who were discharged
      alive from hospital was 42% for cardiac arrest patients, 62% for respiratory
      arrest and 87% for the remaining patients. Among patients with a cardiac arrest,
      those found in ventricular fibrillation/ventricular tachycardia had a survival
      rate of 64%, those found in asystole 24% and those found in pulseless electrical
      activity 10%. Among patients who were being monitored at the time of arrest, the
      survival rate was 52%, as compared with 27% for non-monitored patients (P=
      0.001). Among survivors of cardiac arrest, a cerebral performance category (CPC)
      of 1 (no major deficit) was observed in 81% at discharge and in 82% on admission
      to hospital prior to the arrest. CONCLUSION: We conclude that, during a 14-month
      period at Sahlgrenska University Hospital in Goteborg, almost half the patients
      with a cardiac arrest in which the CPR team was called were discharged from
      hospital. Among survivors, 81% had a CPC score of 1 at hospital discharge.
      Survival seems to be closely related to the relative effectiveness of the
      resuscitation organisation in different parts of the hospital.

PMID- 9918446
TI  - A comparison of transthoracic impedance using standard defibrillation paddles and
      self-adhesive defibrillation pads.
AB  - The success of defibrillation is related to transmyocardial current. This current
      is inversely proportional to transthoracic impedance (TTI). A similar TTI between
      different pads and paddles is important to deliver a consistent therapeutic dose
      to all subjects. Failure to do so may result in either insufficient or excessive
      transmyocardial current leading to a risk of failed defibrillation or tissue
      damage respectively. Several different types of defibrillation paddles and self
      adhesive defibrillation pads are currently available for clinical use but the TTI
      achieved with each type has not been established. We measured TTI using two types
      of commonly used paddles and self-adhesive pads to establish whether any
      significant differences exist between the products. TTI in 40 adult males was
      measured using defibrillation paddles and self-adhesive defibrillation pads
      placed in the antero-apical position. Measurements were made using a 30 kHz low
      amplitude AC current and taken at end-expiration. Mean TTI (omega)+/-S.D. was
      68.2+/-16.1 (Hewlett Packard paddles; A), 62.8+/-13.2 (Hewlett Packard pads; B),
      64.6+/-14.3 (PhysioControl paddles; C) and 95.6+/-22.3 (PhysioControl pads; D).
      Significant differences existed between all groups (P < 0.05) except between B
      and C. Differences in TTI between A, B and C were small and probably of no
      clinical significance. TTI in group D is significantly larger. Although
      transmyocardial current is related to TTI, the relationship is complex and
      differences in TTI alone cannot predict the outcome from defibrillation.

PMID- 9918448
TI  - Measurement of myocardial contractility following successful resuscitation:
      quantitated left ventricular systolic function utilising non-invasive wall stress
      analysis.
AB  - After successful resuscitation from cardiac arrest, prolonged contractile failure
      has been demonstrated in animal experiments. No systematic evaluation of
      myocardial contractility following successful resuscitation after human cardiac
      arrest exists. The aim of this study was to assess left ventricular contractility
      following human cardiac arrest with successful resuscitation. In 20 adult
      patients after cardiac arrest and in four control patients, the relation between
      meridional wall stress (MWS) and rate-corrected mean velocity of circumferential
      fibre shortening (Vcf(c)), a load independent and rate corrected index of left
      ventricular contractility was measured within 4 h after return of spontaneous
      circulation and after 24 h by means of transoesophageal echocardiography. As the
      normal values of Vcf(c) depend on MWS, a normal deviate (z) was calculated. A
      normal z-score is defined as 0+/-2, < -2 indicates reduced contractility, > + 2
      increased contractility. Data are presented as median and the interquartile range
      (IQR). For the comparison of related samples the Wilcoxon sign test was used. In
      most patients after cardiac arrest contractility was severely impaired within 4 h
      after successful resuscitation [z - 7.0 (IQR - 8.9 - (-2.5))]. Contractility did
      not significantly improve within the observational period [z after 24 h - 3.7
      (IQR - 7.9 - (-1.8))] (P = 0.3). The four control patients had normal left
      ventricular contractility on arrival (z 0.0, range - 0.9-0.8) and after 24 h (z
      0.7, range - 1.5-2.7). In conclusion non-invasive wall stress analysis can be
      applied to quantitate systolic left ventricular function, which was severely
      compromised in most patients within the first 24 h after successful
      resuscitation. Whether depression of left ventricular function is caused by
      cardiac arrest itself or by the underlying disease remains speculative.

PMID- 9918447
TI  - Successful automatic external defibrillator operation by people trained only in
      basic life support in a simulated cardiac arrest situation.
AB  - OBJECTIVE: To show whether in an in-hospital cardiac arrest, early defibrillation
      can also be performed by hospital staff trained only in basic life support.
      BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) endorses
      the concept that in many settings non-medical individuals should be allowed and
      encouraged to use defibrillators. METHODS: Five different groups of hospital
      staff were evaluated whether they were able to correctly operate an automatic
      external defibrillator in a simulated sudden cardiac arrest situation without any
      prior instruction. The participants were assigned either to the 'basic life
      support-trained' group (BLS, n = 40, or to the 'advanced life support-trained'
      group (ALS, n = 40). RESULTS: All persons of the 'only BLS-trained' group
      delivered the three sequential ('stacked') shocks with the automatic external
      defibrillator when persistent ventricular fibrillation was simulated. The 'ALS
      trained' persons successfully delivered the three shocks with the automatic
      external defibrillator in 98% of the cases. When this group used a conventional
      defibrillator, only 88% were able to deliver the three shocks, however they were
      able to do it significantly more quickly. CONCLUSION: Using an automatic
      defibrillator without any prior instruction, even persons trained only in BLS
      were able to deliver three sequential shocks in a simulated persistent
      ventricular fibrillation cardiac arrest.

PMID- 9918449
TI  - Preliminary clinical outcome study of mild resuscitative hypothermia after out-of
      hospital cardiopulmonary arrest.
AB  - The effects of mild hypothermia (MH) were investigated. From 1995 to 1996, 28
      adult patients with out-of-hospital cardiopulmonary arrest (CPA) had return of
      spontaneous circulation and survived for more than two days. Thirteen patients
      were in the MH group. In the MH group, core temperature was maintained between 33
      and 34 degrees C for 48 h, and then re-warmed to a temperature of 37 degrees C,
      at a rate of no greater than 1 degrees C per day. Fifteen patients, admitted
      before the MH protocol was instituted, were in the control group. Despite the
      fact that the number of witnessed arrests in the control group were greater than
      in the MH group, there were both more survivors (7/13 vs. 5/15) and more fully
      recovered patients (3/13 vs. 1/15) in the MH vs Control groups. Eleven of 13 MH
      patients, as compared to 6/15 controls developed pneumonia. Our study, although
      preliminary, suggests that MH might confer improved outcome, as has been shown in
      animal models, after CPA. This treatment is associated with an increase in
      pneumonic complications.

PMID- 9918450
TI  - Carbon dioxide levels during pre-hospital active compression--decompression
      versus standard cardiopulmonary resuscitation.
AB  - In a prospective randomised study we investigated end-tidal carbon dioxide levels
      during standard versus active compression-decompression (ACD) cardiopulmonary
      resuscitation (CPR) assuming that the end-tital carbon dioxide reflects cardiac
      output during resuscitation. In each group 60 patients with out-of-hospital
      cardiac arrest were treated either with the standard or the ACD method. End-tidal
      CO2 (p(et)CO2, mmHg) was assessed with a side-stream capnometer following
      intubation and then every 2 min up to 10 min or restoration of spontaneous
      circulation (ROSC). There was no difference in p(et)CO2 between both patient
      groups. However, CO2 was significantly higher in patients who were admitted to
      hospital as compared to patients declared dead at the scene. All of the admitted
      patients had a p(et)CO2 of at least 15 mmHg no later than 2 min following
      intubation, none of the dead patients ever exceeded 15.5 mmHg. From these data we
      conclude that capnometry adds valuable information to the estimation of a
      patient's prognosis in the field (threshold, 15 mmHg), but we could not detect
      any difference in p(et)CO2 between ACD and standard CPR.

PMID- 9918451
TI  - Modification of the closed circuit underwater breathing apparatus LAR V makes it
      suitable for cardiopulmonary resuscitation (CPR).
AB  - This pilot study was carried out in order to determine whether or not a modified
      closed circuit underwater oxygen rebreathing device could serve as an adjunct for
      ventilation during CPR in remote locations. As a control a common self-inflating
      bag valve ventilation device was used. METHODS: A total of 20 combat divers were
      enrolled, of whom 18 met the criteria to be included in two-rescuer CPR manikin
      training. A modified LAR V (Drager, Germany), a closed circuit underwater
      breathing apparatus, that uses pure oxygen, and a conventional Ambu Mark III bag
      were used for artificial mask-ventilation in a randomised crossover design. A
      total of ten cycles of CPR were analysed. RESULTS: Of the divers, 17 were able to
      ventilate with the modified LAR V. The median tidal volumes were lower with LAR V
      versus Ambu (725 vs 800 ml; P = 0.04) and median total time required was
      significantly longer with LAR V versus Ambu (90 vs 68.5 s; P = 0.004). Gastric
      inflation was associated only with the Ambu. CONCLUSIONS: This modification of
      the LAR V makes it suitable for CPR performed by military divers when
      conventional ventilatory devices are not available. It would be necessary,
      however, to teach the proper use of the modified ventilation mode and to provide
      repeated training.

PMID- 9918453
TI  - Identification of rib cage's lower margin in cardiopulmonary resuscitation.
AB  - The Guidelines of the American Heart Association (J Am Med Assoc
      1992;268(16):2184-2198) and the European Resuscitation Council (Resuscitation
      1992;24:103-110; Resuscitation 1998;37:67-80) for adult basic cardiopulmonary
      resuscitation (CPR), suggest that the hands of the rescuer should be positioned
      on the sternum of the victim after identification of the lower margin of the rib
      cage, but how this identification is made is not described. Lay persons have
      problems with the identification of anatomical structures that they cannot
      actually see (Bahr et al., Resuscitation 1997;35:23-6). Although this does not
      present a problem for those familiar with human anatomy, we have noticed that lay
      persons have problems with the identification of the lower margin of the rib
      cage. In this report, we suggest a method for correct and rapid recognition of
      the costal margin.

PMID- 9918452
TI  - ResusSim 98--a PC advanced life support trainer.
AB  - Advanced life support (ALS) requires several different skills and the recall of
      complex information. The personal computer is an ideal tool for the teaching of
      factual information. We have developed a computer programme that simulates a
      variety of cardiac arrest scenarios. Its aim is to communicate specialist
      knowledge to junior staff in a challenging and entertaining way. Each scenario
      has a real time ECG, clinical signs of the simulated patient, blood pressure,
      oxygen saturation and temperature. Arterial blood samples can be analysed and the
      medical record can be reviewed. Interventions available include defibrillation,
      intubation, fluid and drug therapy. Built-in variation means that repeating a
      scenario may lead to different patient behaviour. An important part of the
      programme is the intelligent debriefing of the user after each patient. Each
      action elicits a comment that is based upon the current European Resuscitation
      Council guidelines. This is then hyperlinked to an extensive help file that
      includes the text of the guidelines, diagrams, pictures and algorithms that aid
      the user in the learning of ALS skills in association with existing teaching
      programmes. ResusSim 98 runs under Windows 3.1, Windows 95/98 and Windows NT 4.0.

PMID- 9918454
TI  - Resuscitation training for medical students.
AB  - This paper describes the systematic training of undergraduate medical students in
      resuscitation skills, aimed at overcoming the well known deficiencies in the
      resuscitation skills of junior doctors. This training can be integrated with the
      medical curriculum, but takes a considerable commitment in teaching time. To give
      each of our 240 medical students 36 h of resuscitation training, including an
      advanced life support (ALS) course for all students, 2442 h of teacher's time is
      required each year. It is important that teaching is continued on the wards as
      part of the training of pre-registration house officers. The amount of teaching
      time required justifies the appointment of Medical School Resuscitation Officers,
      dedicated to teaching medical students, dental students and pre-registration
      house officers.

PMID- 9918455
TI  - Failure of glutathione peroxidase to reduce transient ischemic injury in the rat
      hippocampal CA1 subfield.
AB  - It has been postulated that oxygen radical species are produced by ischemia
      reperfusion in the brain and play a critical role in neuronal damage. Glutathione
      peroxidase (GSHPx), one of the antioxidative enzymes, detoxifies hydrogen
      peroxide, which is the source of a hydroxyl radical that reacts with
      polyunsaturated fatty acids of the cell membrane, resulting in cell death. The
      present study was undertaken to investigate the postischemic effect of exogenous
      GSHPx upon rats subjected to global forebrain ischemia and reperfusion. GSHPx or
      artificial cerebrospinal fluid (aCSF) as a vehicle for GSHPx was administered
      into the left cerebral ventricle 15 min after a 5-min 4-vessel occlusion.
      Neuronal damage and apoptosis were assessed 4 days after ischemic insult using
      cresyl violet stain and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) method, respectively. Most pyramidal neurons in the
      hippocampal CA1 subfield were degenerated and their nuclei were stained by the
      TUNEL in both GSHPx- (80 and 200 units/kg) and aCSF-treated animals. Neurons in
      other subfields of the hippocampus and dentate gyrus survived. Our further
      attempt to improve the outcome with a higher dose of GSHPx was unsuccessful
      because all rats receiving 400 units/kg died soon after the
      intracerebroventricular injection due to respiratory insufficiency. We conclude
      that the postischemic treatment with GSHPx does not ameliorate the apoptotic
      neuronal death of hippocampal CA1 in this transient ischemia model under the
      conditions used here.

PMID- 9918456
TI  - An ultrastructural study into the effect of global transient cerebral ischaemia
      on the synaptic population of the cerebellar cortex in rats.
AB  - The density of synapses, the shape and size of presynaptic dense projections
      (PDP), and the curvature of synaptic appositions in the molecular layer of the
      cerebellum cortex of rat at 10 min ischaemia and after 90 min, 1, 3, 7, 30 days
      of re-circulation were examined using quantitative ultra-structural techniques.
      The numerical density of mature junctions decreased significantly (44.0%) after 1
      and 3 days of re-circulation, and was increased to 149.8% of the value in the
      control animals after 7 days of re-circulation. The restoration of the population
      of mature synaptic junctions was accompanied by a considerable increase of the
      number of immature junctions. We found a close association between the synaptic
      curvature and the size of PDP. The curvature of the larger junctions was
      consistently associated with a reduced height of PDP and a rounder shape.
      Synaptic curvature increased from 0.0885 (control) to 0.2041 (3 days of re
      circulation) and to 0.2128 (7 days re-circulation). The maximum reduction in
      synaptic numerical density and larger junction curvature was found in zones of
      irreversibly damaged Purkinje cells. Our results revealed that the synaptic
      curvature and the height of the pre-synaptic dense projections undergo reciprocal
      changes after global transient cerebral ischemia. It is tempting to hypothesize
      that the positive synaptic curvature occurs as a result of changes in
      morphological conditions for the PDP filaments and in the shape and size of PDP
      and depends on the level of Ca2+ in synaptic appositions.

PMID- 9918457
TI  - Changes in oxidative stress in the rat brain during post-cardiac arrest
      reperfusion, and the effect of treatment with the free radical scavenger
      idebenone.
AB  - The study was designed to determine the effect of idebenone, an electron-trapping
      agent and free radical scavenger capable of crossing the blood-brain barrier, on
      cardiac arrest-induced oxidative brain stress. Stress indices used were the brain
      contents of thiobarbituric acid-reactive material (TBAR), conjugated dienes and
      protein and non-protein thiols. Twenty-four hours after receiving one oral dose
      of placebo or 100 mg kg(-1) idebenone, the rats were anaesthetized with diethyl
      ether and either decapitated immediately, or subjected to 7.5 min cardiac arrest
      induced by compression of the heart vessel bundle. The next groups of rats were
      sacrificed at the end of the cardiac arrest session, or resuscitated by external
      chest compression and artificial ventilation with air and sacrificed 15 min, 60
      min, 24 h, and 72 h later while re-anesthetized with diethyl ether. Subsequent
      placebo or idebenone (100 mg kg(-1)) doses were given to the appropriate
      surviving rats once daily, beginning 8-10 min after the end of cardiac arrest
      session. Compared to pre-arrest values, TBAR and conjugated dienes' contents
      increased, respectively, by 339 and 286%, and protein and non-protein thiol
      contents decreased, respectively, by 69 and 85% within 60 min after the
      resuscitation in placebo-treated rats. Normalization of all oxidative stress
      indices in these rats was slow and incomplete even at 72 h. Idebenone treated
      rats showed no increase in TBAR contents, and a marked attenuation of changes in
      the other indices. These results show that oral idebenone greatly reduces
      oxidative brain stress following transient circulatory arrest in the rat. This
      effect could not be explained by simple stoichiometric scavenging of free
      radicals. Possible mechanisms of idebenone action are discussed.

PMID- 9918458
TI  - Experimental model of cardiovascular post-resuscitation syndrome--no effect of
      platelet activating factor antagonism.
AB  - The cardiovascular instability seen in the reperfusion phase after resuscitation
      from cardiac arrest may contribute to secondary brain injury. The aim of the
      present study was to characterise post-resuscitation cardiovascular instability
      in an experimental model of cardiac arrest and to test if cardiovascular
      stability could be improved by pre-treatment with the platelet activating factor
      (PAF) antagonist BN52021. Ten anaesthetised pigs received pre-treatment with
      BN52021 before induction of ventricular fibrillation (arrest/BN52021 group),
      while ten animals received only the vehicle (arrest/vehicle group). After a non
      intervention interval of 9 min, resuscitation was attempted. Resuscitated animals
      were observed for 5 h and compared to a sham arrest group of seven animals. The
      haemodynamic situation after resuscitation was characterised by a low cardiac
      output that was inadequate in relation to the oxygen demand, as reflected by a
      low mixed venous oxygen saturation. The arterial blood pressure was to some
      extent reduced and the filling pressures in both the right and left heart were
      increased, but urinary output was not reduced. The severe haemodynamic compromise
      was not adequately reflected by standard monitoring variables such as arterial
      blood pressure and urinary output. Pre-treatment with BN52021 was unable to
      improve any aspect of short-term survival or haemodynamic stability.

PMID- 9918459
TI  - Unexpected return of spontaneous circulation after cessation of resuscitation
      (Lazarus phenomenon)
AB  - Since 1982, more than 20 patients with return of spontaneous circulation after
      cessation of cardiopulmonary resuscitation (Lazarus phenomenon) have been
      published. We report on another case here. Such cases are probably underreported
      due to medicolegal concerns. After cessation of resuscitation, each patient
      should be further monitored for at least 10 min to detect a possible Lazarus
      phenomenon.

PMID- 9918460
TI  - An interesting complication of the Heimlich manoeuvre.
AB  - The removal of inhaled foreign bodies using the Heimlich manoeuvre is recommended
      as part of the immediate management of the choking child. We report on a case of
      witnessed laryngeal obstruction by a foreign body in which repeated Heimlich
      manoeuvres failed to expel the foreign body, but temporarily relieved the
      obstruction. The repeated Heimlich manoeuvres dislodged the foreign body into the
      trachea and may have contributed to the rapid development of extensive surgical
      emphysema, pneumomediastinum and pneumopericardium. The purpose of this report is
      to demonstrate that the Heimlich manoeuvre was effective in relieving the airway
      obstruction, but was associated with potentially severe complications.

PMID- 9918461
TI  - A piece of my mind. Underlying cause.

PMID- 9918462
TI  - "New Look" reflects changing style of patient safety enhancement.

PMID- 9918463
TI  - Learning lessons from true-life school trauma.

PMID- 9918464
TI  - From the Surgeon General. Polio eradication by the year 2000.

PMID- 9918465
TI  - From the Centers for Disease Control and Prevention. Impact of the sequential
      IPV/OPV schedule on vaccination coverage levels--United States, 1997.

PMID- 9918467
TI  - From the Centers for Disease Control and Prevention. FDA approval of a fourth
      acellular pertussis vaccine for use among infants and young children.

PMID- 9918469
TI  - Responding to patient requests for physician-assisted suicide.

PMID- 9918466
TI  - From the Centers for Disease Control and Prevention. Osteoporosis among estrogen
      deficient women--United States, 1988-1994.

PMID- 9918468
TI  - Responding to patient requests for physician-assisted suicide.

PMID- 9918470
TI  - Responding to patient requests for physician-assisted suicide.

PMID- 9918471
TI  - Responding to patient requests for physician-assisted suicide.

PMID- 9918472
TI  - Sunlight exposure and cataract.

PMID- 9918473
TI  - Sunlight exposure and cataract.

PMID- 9918474
TI  - Mental health of women in Afghanistan.

PMID- 9918475
TI  - Time to clinical stability for patients with community-acquired pneumonia.

PMID- 9918476
TI  - Hospitalizations for dog bite injuries.

PMID- 9918477
TI  - Treatment of smokeless tobacco addiction with bupropion and behavior
      modification.

PMID- 9918478
TI  - Weight control and risk factor reduction in obese subjects treated for 2 years
      with orlistat: a randomized controlled trial.
AB  - CONTEXT: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat
      absorption by approximately 30%, may promote weight loss and reduce
      cardiovascular risk factors. OBJECTIVE: To test the hypothesis that orlistat
      combined with dietary intervention is more effective than placebo plus diet for
      weight loss and maintenance over 2 years. DESIGN: Randomized, double-blind,
      placebo-controlled study conducted from October 1992 to October 1995. SETTING AND
      PARTICIPANTS: Obese adults (body mass index [weight in kilograms divided by the
      square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers.
      INTERVENTION: Subjects received placebo plus a controlled-energy diet during a 4
      week lead-in. On study day 1, the diet was continued and subjects were randomized
      to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks.
      After 52 weeks, subjects began a weight-maintenance diet, and the placebo group
      (n = 133) continued to receive placebo and orlistat-treated subjects were
      rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n =
      152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks. MAIN OUTCOME
      MEASURES: Body weight change and changes in blood pressure and serum lipid,
      glucose, and insulin levels. RESULTS: A total of 1187 subjects entered the
      protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For
      intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated
      subjects were evaluated. During the first year orlistat-treated subjects lost
      more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/
      0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during
      year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2%
      regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain),
      or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with
      orlistat, 120 mg 3 times a day, was associated with improvements in fasting low
      density lipoprotein cholesterol and insulin levels. CONCLUSIONS: Two-year
      treatment with orlistat plus diet significantly promotes weight loss, lessens
      weight regain, and improves some obesity-related disease risk factors.

PMID- 9918479
TI  - Safety of revaccination with pneumococcal polysaccharide vaccine.
AB  - CONTEXT: Revaccination of healthy adults with pneumococcal polysaccharide vaccine
      (PPV) within several years of first vaccination has been associated with a higher
      than expected frequency and severity of local injection site reactions. The risk
      of adverse events associated with revaccination of elderly and chronically ill
      persons 5 or more years after first vaccination, as is currently recommended, has
      not been well defined. OBJECTIVE: To determine whether revaccination with PPV at
      least 5 years after first vaccination is associated with more frequent or more
      serious adverse events than those following first vaccination. DESIGN:
      Comparative intervention study conducted between April 1996 and August 1997.
      PARTICIPANTS: Persons aged 50 to 74 years either who had never been vaccinated
      with PPV (n = 901) or who had been vaccinated once at least 5 years prior to
      enrollment (n = 513). INTERVENTION: PPV vaccination. MAIN OUTCOME MEASURES:
      Postvaccination local injection site reactions and prevaccination concentrations
      of type-specific antibodies. RESULTS: Those who were revaccinated were more
      likely than those who received their first vaccinations to report a local
      injection site reaction of at least 10.2 cm (4 in) in diameter within 2 days of
      vaccination: 11% (55/513) vs 3% (29/901) (relative risk [RR], 3.3; 95% confidence
      interval [CI], 2.1-5.1). These reactions resolved by a median of 3 days following
      vaccination. The highest rate was among revaccinated patients who were
      immunocompetent and did not have chronic illness: 15% (33/228) compared with 3%
      (10/337) among comparable patients receiving their first vaccinations (RR, 4.9;
      95% CI, 2.4-9.7). The risk of these local reactions was significantly correlated
      with prevaccination geometric mean antibody concentrations. CONCLUSIONS:
      Physicians and patients should be aware that self-limited local injection site
      reactions occur more frequently following revaccination compared with first
      vaccination; however, this risk does not represent a contraindication to
      revaccination with PPV for recommended groups.

PMID- 9918480
TI  - Prevalence of lysosomal storage disorders.
AB  - CONTEXT: Lysosomal storage disorders represent a group of at least 41 genetically
      distinct, biochemically related, inherited diseases. Individually, these
      disorders are considered rare, although high prevalence values have been reported
      in some populations. These disorders are devastating for individuals and their
      families and result in considerable use of resources from health care systems;
      however, the magnitude of the problem is not well defined. To date, no
      comprehensive study has been performed on the prevalence of these disorders as a
      group. OBJECTIVE: To determine the prevalence of lysosomal storage disorders
      individually and as a group in the Australian population. DESIGN: Retrospective
      case studies. SETTING: Australia, from January 1, 1980, through December 31,
      1996. MAIN OUTCOME MEASURE: Enzymatic diagnosis of a lysosomal storage disorder.
      RESULTS: Twenty-seven different lysosomal storage disorders were diagnosed in 545
      individuals. The prevalence ranged from 1 per 57000 live births for Gaucher
      disease to 1 per 4.2 million live births for sialidosis. Eighteen of 27 disorders
      had more than 10 diagnosed cases. As a group of disorders, the combined
      prevalence was 1 per 7700 live births. There was no significant increase in the
      rate of either clinical diagnoses or prenatal diagnoses of lysosomal storage
      disorders during the study period. CONCLUSIONS: Individually, lysosomal storage
      disorders are rare genetic diseases. However, as a group, they are relatively
      common and represent an important health problem in Australia.

PMID- 9918481
TI  - A program to increase the number of family physicians in rural and underserved
      areas: impact after 22 years.
AB  - CONTEXT: The shortage of physicians in rural areas is a longstanding and serious
      problem, and national and state policymakers and educators continue to face the
      challenge of finding effective ways to increase the supply of rural physicians.
      OBJECTIVE: To determine the direct and long-term impact of the Physician Shortage
      Area Program (PSAP) of Jefferson Medical College (JMC) on the rural physician
      workforce. DESIGN: Retrospective cohort study. PARTICIPANTS AND SETTING: A total
      of 206 PSAP graduates from the classes of 1978 to 1991. MAIN OUTCOME MEASURES:
      The PSAP graduates currently practicing family medicine in rural and underserved
      areas of Pennsylvania, compared with all allopathic medical school graduates in
      the state, and with all US and international allopathic graduates. All PSAP
      graduates were also compared with their non-PSAP peers at JMC regarding their US
      practice location, medical specialty, and retention for the past 5 to 10 years.
      RESULTS: The PSAP graduates account for 21% (32/150) of family physicians
      practicing in rural Pennsylvania who graduated from one of the state's 7 medical
      schools, even though they represent only 1% (206/14710) of graduates from those
      schools (relative risk [RR], 19.1). Among all US and international medical school
      graduates, PSAP graduates represent 12% of all family physicians in rural
      Pennsylvania. Results were similar for PSAP graduates practicing in underserved
      areas. Overall, PSAP graduates were much more likely than their non-PSAP
      classmates at JMC to practice in a rural area of the United States (34% vs 11%;
      RR, 3.0), to practice in an underserved area (30% vs 9%; RR, 3.2), to practice
      family medicine (52% vs 13%; RR, 4.0), and to have combined a career in family
      practice with practice in a rural area (21% vs 2%; RR, 8.5). Of PSAP graduates,
      84% were practicing in either a rural or small metropolitan area, or one of the
      primary care specialties. Program retention has remained high, with the number of
      PSAP graduates currently practicing rural family medicine equal to 87% of those
      practicing between 5 and 10 years ago, and the number practicing in underserved
      areas, 94%. CONCLUSIONS: The PSAP, after more than 22 years, has had a
      disproportionately large impact on the rural physician workforce, and this effect
      has persisted over time. Based on these program results, policymakers and medical
      schools can have a substantial impact on the shortage of physicians in rural
      areas.

PMID- 9918482
TI  - Efficacy of antiseptic-impregnated central venous catheters in preventing
      catheter-related bloodstream infection: a meta-analysis.
AB  - CONTEXT: Central venous catheters impregnated with chlorhexidine and silver
      sulfadiazine have recently been introduced for the prevention of catheter-related
      infections. However, there remains some uncertainty regarding the efficacy of
      these catheters because of conflicting reports in the literature. OBJECTIVE: To
      evaluate the efficacy of chlorhexidine-silver sulfadiazine-impregnated central
      venous catheters in the prevention of catheter-related bloodstream infection.
      DATA SOURCES: Studies identified from a computerized search of the MEDLINE
      database from January 1966 to January 1998, reference lists of identified
      articles, and queries of principal investigators and the catheter manufacturer.
      STUDY SELECTION: Randomized trials comparing chlorhexidine-silver sulfadiazine
      impregnated central venous catheters with nonimpregnated catheters were included.
      The outcomes assessed were catheter colonization and catheter-related bloodstream
      infection confirmed by catheter culture. DATA EXTRACTION: Twelve studies met the
      inclusion criteria for catheter colonization and included a total of 2611
      catheters. Eleven studies with a total of 2603 catheters met the inclusion
      criteria for catheter-related bloodstream infection. Most patients in these
      studies were from groups considered to be at high risk for catheter-related
      infections. Summary statistics were calculated using Mantel-Haenszel methods
      under a fixed-effects model. DATA SYNTHESIS: The summary odds ratio for catheter
      colonization was 0.44 (95% confidence interval [CI], 0.36-0.54; P<.001),
      indicating a significant decrease in catheter colonization associated with
      impregnated catheters. The studies examining the outcome of primary interest,
      catheter-related bloodstream infection, had a summary odds ratio of 0.56 (95% CI,
      0.37-0.84; P = .005). CONCLUSIONS: Central venous catheters impregnated with a
      combination of chlorhexidine and silver sulfadiazine appear to be effective in
      reducing the incidence of both catheter colonization and catheter-related
      bloodstream infection in patients at high risk for catheter-related infections.

PMID- 9918483
TI  - Clinical loyalties and the social purposes of medicine.
AB  - Physicians increasingly face conflicts between the ethic of undivided loyalty to
      patients and pressure to use clinical methods and judgment for social purposes
      and on behalf of third parties. The principal legal and ethical paradigms by
      which these conflicts are managed are inadequate, because they either deny or
      unsuccessfully finesse the reality of contradiction between fidelity to patients
      and society's other expectations of medicine. This reality needs to be more
      squarely acknowledged. The challenge for ethics and law is not to resolve this
      tension--an impossible task--but to mediate it in myriad clinical circumstances
      in a way that preserves the primacy of keeping faith with patients while
      conceding the legitimacy of society's other expectations of medicine.

PMID- 9918484
TI  - Would you say you "had sex" if...?
AB  - CONTEXT: The current public debate regarding whether oral sex constitutes having
      "had sex" or sexual relations has reflected a lack of empirical data on how
      Americans as a population define these terms. OBJECTIVE: To determine which
      interactions individuals would consider as having "had sex." METHODS: A question
      was included in a survey conducted in 1991 that explored sexual behaviors and
      attitudes among a random stratified sample of 599 students representative of the
      undergraduate population of a state university in the Midwest. PARTICIPANTS: The
      participants originated from 29 states, including all 4 US Census Bureau
      geographic regions. Approximately 79% classified themselves as politically
      moderate to conservative. MAIN OUTCOME MEASURE: Percentage of respondents who
      believed the interaction described constituted having "had sex." RESULTS:
      Individual attitudes varied regarding behaviors defined as having "had sex": 59%
      (95% confidence interval, 54%-63%) of respondents indicated that oral-genital
      contact did not constitute having "had sex" with a partner. Nineteen percent
      responded similarly regarding penile-anal intercourse. CONCLUSIONS: The findings
      support the view that Americans hold widely divergent opinions about what
      behaviors do and do not constitute having "had sex."

PMID- 9918485
TI  - Pharmacotherapy for obesity.

PMID- 9918486
TI  - Revaccination of high-risk adults with pneumococcal polysaccharide vaccine.

PMID- 9918487
TI  - Soliciting the patient's agenda: have we improved?
AB  - CONTEXT: Previous research indicates physicians frequently choose a patient
      problem to explore before determining the patient's full spectrum of concerns.
      OBJECTIVE: To examine the extent to which experienced family physicians in
      various practice settings elicit the agenda of concerns patients bring to the
      office. DESIGN: A cross-sectional survey using linguistic analysis of a
      convenience sample of 264 patient-physician interviews. SETTING AND PARTICIPANTS:
      Primary care offices of 29 board-certified family physicians practicing in rural
      Washington (n = 1; 3%), semirural Colorado (n = 20; 69%), and urban settings in
      the United States and Canada (n = 8; 27%). Nine participants had fellowship
      training in communication skills and family counseling. MAIN OUTCOME MEASURES:
      Patient-physician verbal interactions, including physician solicitations of
      patient concerns, rate of completion of patient responses, length of time for
      patient responses, and frequency of late-arising patient concerns. RESULTS:
      Physicians solicited patient concerns in 199 interviews (75.4%). Patients'
      initial statements of concerns were completed in 74 interviews (28.0%).
      Physicians redirected the patient's opening statement after a mean of 23.1
      seconds. Patients allowed to complete their statement of concerns used only 6
      seconds more on average than those who were redirected before completion of
      concerns. Late-arising concerns were more common when physicians did not solicit
      patient concerns during the interview (34.9% vs 14.9%). Fellowship-trained
      physicians were more likely to solicit patient concerns and allow patients to
      complete their initial statement of concerns (44% vs 22%). CONCLUSIONS:
      Physicians often redirect patients' initial descriptions of their concerns. Once
      redirected, the descriptions are rarely completed. Consequences of incomplete
      initial descriptions include late-arising concerns and missed opportunities to
      gather potentially important patient data. Soliciting the patient's agenda takes
      little time and can improve interview efficiency and yield increased data.

PMID- 9918488
TI  - JAMA patient page: weight management.

PMID- 9918489
TI  - Sequencing and functional analysis of the yeast genome.
AB  - The genome of the yeast Saccharomyces cerevisiae was sequenced by an
      international consortium of laboratories from Europe, Canada, the U.S.A. and
      Japan. This project is now finished and the complete sequence of the first
      eukaryotic genome was released to the public data bases in April 1996. An
      overview and preliminary analysis of the entire genome sequence was presented in
      a special issue of Nature in May 1997, entitled "The yeast genome directory". At
      its origin the Yeast Genome Sequencing Project provoked much debate and
      controversy; however, the final results obtained and the insights this has given
      us into the organisation and content of a eukaryotic genome have more than
      justified the expectations of the supporters of the project. The importance of
      genomic sequencing and analysis, especially of model organisms, is now widely
      accepted and this has resulted in the birth of the new science of genomics
      (Botstein & Cherry, 1997, Proc. Natl. Acad. Sci. U.S.A. 94, 5506). The
      information from gene and protein sequences ultimately lead to functional
      description of all genes. The main strategies describing possible ways to analyse
      the function of new genes that have been identified by systematic sequencing of
      Saccharomyces cerevisiae genome are described.

PMID- 9918490
TI  - Overexpression of the yeast HAM1 gene prevents 6-N-hydroxylaminopurine
      mutagenesis in Escherichia coli.
AB  - The base analogue 6-N-hydroxylaminopurine (HAP) is a potent mutagen in a variety
      of prokaryotic and eukaryotic organisms. Mutations in the yeast ham1 gene render
      the cells hypersensitive to the mutagenic effect of HAP. We have found that this
      gene has homologues in a variety of organisms from bacteria to man. We have
      overexpressed yeast Ham1p in E. coli. We demonstrate that under conditions when
      this protein constitutes approximately 30% of cellular protein, the host strain
      is protected both from toxic and mutagenic effects of HAP. This result indicates
      that sole Ham1p activity might be sufficient for destruction of HAP or its
      metabolites in bacterial cells.

PMID- 9918491
TI  - Recombinant His-tagged DNA polymerase. I. Cloning, purification and partial
      characterization of Thermus thermophilus recombinant DNA polymerase.
AB  - The Tth DNA polymerase gene from the thermophilic Thermus thermophilus (strain
      HB8) was amplified, cloned and expressed in Escherichia coli. The recombinant DNA
      polymerase containing a polyhistidine tag at the N-terminus was isolated in a
      single step by Ni2+ affinity chromatography. The purified recombinant enzyme,
      showing high polymerase activity contained 43 additional amino-acid residues
      (including a cluster of six histidine residues inserted for purification of the
      recombinant protein by metal-affinity chromatography) at N-terminus. The applied
      overexpression system was very efficient giving 700,000 u of DNA polymerase
      activity from 1 liter of induced culture. The enzyme was characterized and
      displayed high DNA polymerase and reverse transcriptase activities and high
      thermostability as compared to the native Tth DNA polymerase.

PMID- 9918492
TI  - Recombinant His-tagged DNA polymerase. II. Cloning and purification of Thermus
      aquaticus recombinant DNA polymerase (Stoffel fragment).
AB  - The Stoffel DNA fragment, shortened by 12 bp from 5' end, coding for Stoffel DNA
      polymerase (missing 4 amino acids at N-terminus of Stoffel amino-acids sequence)
      from the thermophilic Thermus aquaticus (strain YT-1) was amplified, cloned and
      expressed in Escherichia coli. The recombinant Stoffel fragment contained a
      polyhistidine tag at the N-terminus (21 additional amino acids) that allowed its
      single-step isolation by Ni2+ affinity chromatography. The enzyme was
      characterized and displayed high DNA polymerase activity and thermostability
      evidently higher than the native Taq DNA polymerase.

PMID- 9918493
TI  - Cloning and sequencing of cDNA encoding the rice methionyl-tRNA synthetase.
AB  - Three overlapping clones of cDNA, Mos43, Mos28 and Mos60, coding for methionyl
      tRNA synthetase were obtained by screening the Oryza sativa lambda gt11 library.
      Their nucleotide sequence of 2850 bp was determined. The deduced amino-acid
      sequence of the isolated clones contains a HLGN and KFSKS motifs, which are
      conserved for this family of enzymes and have been proposed to be the signature
      sequences for class I aminoacyl-tRNA synthetases. A comparison of the rice MetRS
      primary structure with those deposited in EMBL/GenBank points to its high
      homology to yeast, human and Caenorhabditis elegans MetRSs. Interestingly, a
      great similarity of its C terminus to endothelial-monocyte-activating polypeptide
      II (EMAPII) and yeast protein G4p1 was observed.

PMID- 9918494
TI  - Hydrogen peroxide effects in Escherichia coli cells.
AB  - We analyzed DNA lesions produced by H2O2 under low iron conditions, the cross
      adaptive response and the synergistic lethal effect produced by iron chelator-o
      phenanthroline, using different Escherichia coli mutants deficient in DNA repair
      mechanisms. At normal iron levels the lesions produced by H2O2 are repaired
      mainly by the exonuclease III protein. Under low iron conditions we observed that
      the Fpg and UvrA proteins as well as SOS and OxyR systems participate in the
      repair of these lesions. The lethal effect of H2O2 is strengthened by o
      phenanthroline if both compounds are added simultaneously to the culture medium.
      This phenomenon was observed in the wild type cells and in the xthA mutant
      (hypersensitive to H2O2). E. coli cells treated with low concentrations of H2O2
      (micromolar) acquire resistance to different DNA damaging agents. Our results
      indicate also that pretreatment with high (millimolar) H2O2 concentrations
      protects cells against killing, by UV and this phenomenon is independent of the
      SOS system, but dependent on RecA and UvrA proteins. H2O2 induces protection
      against lethal and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG). H2O2 also protects the cells against killing by cumene hydroperoxide,
      possibly with the participation of Ahp protein.

PMID- 9918495
TI  - Thermal profile with alternately raised and lowered annealing temperature
      improves the PCR amplification using highly degenerate primers.
AB  - The proposed here PCR thermal profile improves the specificity and efficiency of
      PCR using highly degenerate primers, especially in the case of larger PCR
      products (around 2000 bp and more). The improvement is achieved by the use of a
      specific annealing temperature in the beginning cycles and the alternate lowering
      and raising of the annealing temperature in the subsequent cycles.

PMID- 9918496
TI  - Conservation of the structure and organization of lupin mitochondrial nad3 and
      rps12 genes.
AB  - A high level of the nucleotide sequence conservation of mitochondrial nad3 and
      rps12 genes was found in four lupin species. The only differences concern three
      nucleotides in the Lupinus albus rps12 gene and three nucleotides insertion in
      the L. mutabilis spacer. Northern blot analysis as well as RT-PCR confirmed
      cotranscription of the L. luteus genes because the transcripts detected were long
      enough.

PMID- 9918497
TI  - Induction of DNA breakage in X-irradiated nucleoids selectively stripped of
      nuclear proteins in two mouse lymphoma cell lines differing in radiosensitivity.
AB  - The role of nuclear proteins in protection of DNA against ionizing radiation and
      their contribution to the radiation sensitivity was examined by an alkaline
      version of comet assay in two L5178Y (LY) mouse lymphoma cell lines differing in
      sensitivity to ionizing radiation. LY-S cells are twice more sensitive to
      ionizing radiation than LY-R cells (D0 values of survival curves are 0.5 Gy and 1
      Gy, respectively). Sequential removal of nuclear proteins by extraction with NaCl
      of different concentrations increased the X-ray induced DNA damage in LY-R
      nucleoids. In contrast, in the radiation sensitive LY-S cell line, depletion of
      nuclear proteins practically did not affect DNA damage. Although there is no
      doubt that the main cause of LYS cells' sensitivity to ionizing radiation is a
      defect in the repair of double-strand breaks, our data support the concept that
      nuclear matrix organisation may contribute to the cellular susceptibility to DNA
      damaging agents.

PMID- 9918498
TI  - Phage display of proteins.
AB  - In recent years the phage display approach has become an increasingly popular
      method in protein research. This method enables the presentation of large peptide
      and protein libraries on the surface of phage particles from which molecules of
      desired functional property(ies) can be rapidly selected. The great advantage of
      this method is a direct linkage between an observed phenotype and encapsulated
      genotype, which allows fast determination of selected sequences. The phage
      display approach is a powerful tool in generating highly potent biomolecules,
      including: search for specific antibodies, determining enzyme specificity,
      exploring protein-protein and protein-DNA interactions, minimizing proteins,
      introducing new functions into different protein scaffolds, and searching
      sequence space of protein folding. In this article many examples are given to
      illustrate that this technique can be used in different fields of protein
      science. The phage display has a potential of the natural evolution and its
      possibilities are far beyond rational prediction. Assuming that we can design the
      selection agents and conditions we should be able to engineer any desired protein
      function or feature.

PMID- 9918499
TI  - Annexins and ATP in membrane traffic: a comparison with membrane fusion
      machinery.
AB  - Annexins, calcium- and membrane-binding multifunctional proteins, have been
      implicated in N-ethylmaleimide (NEM)-independent fusion of vesicular structures
      involved in membrane traffic. This view is based on intracellular localization of
      annexins, which are frequently associated with endosomes, chromaffin granules,
      caveolae, clathrin-coated pits, and other membrane compartments, engaged in endo-
      and exocytosis. Moreover, annexins were found to modulate budding and aggregation
      of vesicle membranes, to interact with cytoskeletal proteins, and, upon binding
      to membranes, to change the structure of lipid bilayer, leading to membrane
      fusion. In addition, some annexins are substrates for various protein kinases
      and, in membrane-bound form, reveal calcium channel activity. Recently, annexins
      were observed to interact in vitro and in vivo with nucleotides, ATP, GTP or
      cAMP, which are potent mediators of membrane traffic processes. In addition,
      annexin VII showed hydrolytic activity towards GTP, and similarities in the
      mechanism of action to that of small GTP-binding proteins were found. The aim of
      the present review is to summarize the observations implying annexins as possible
      effectors in endo- and exocytosis and to compare them with well known complexes
      of cytosolic and membrane proteins forming the true membrane fusion machinery
      within a cell, conserved from yeast to the neurons of humans.

PMID- 9918500
TI  - Adenosine 5'-triphosphate--a new regulator of annexin function. A hypothesis.
AB  - The paradigm of annexins as phospholipid-binding proteins interacting with
      membranes in a calcium-dependent manner has been recently questioned in light of
      observations that some annexin isoforms may behave like membrane integral
      proteins or remain associated with their target membranes at low, resting,
      concentrations of Ca2+ in the cytoplasm. In addition, an evidence has been
      presented that some annexins (annexins I, VI and VII) bind in vitro ATP and GTP,
      and upon binding the nucleotide the in vitro activity of these proteins is
      modified. However, annexins do not contain Walker A and B consensus sequences for
      ATP/GTP binding. This review presents the hypothesis that a new ATP-binding motif
      exists within the annexin molecules and that ATP may play a role of functional
      ligand for annexins also in vivo.

PMID- 9918501
TI  - A cell-free yellow lupin extract containing activities of pseudouridine 35 and 55
      synthases.
AB  - Plant cytoplasmic tyrosine tRNA was pseudouridylated at three different
      positions: 35, 39 and 55. These pseudouridines were introduced by three different
      enzymes--pseudouridine synthases. Variants of the Arabidopsis thaliana pre
      tRNA(Tyr) were constructed that allow to monitor specifically pseudouridylation
      at different nucleotide positions. Using such RNAs to assay pseudouridine
      synthesis we have prepared an extract from Lupinus luteus cv. Ventus seeds
      containing activities of at least psi35 and psi55 synthases. This is the first
      report describing the preparation of the lupin seed extract that specifically
      modifies plant pre-tRNA(Tyr) transcribed by T7 RNA polymerase. U35 is converted
      to psi35 only in an intron-dependent manner, while pseudouridylation of U55 is
      insensitive to the presence or absence of an intron.

PMID- 9918502
TI  - 7-Deazapurine 2'-deoxyribofuranosides are noncleavable competitive inhibitors of
      Escherichia coli purine nucleoside phosphorylase (PNP).
AB  - A series of 7-deazapurine 2'-deoxyribofuranosides were synthesized according to
      already known procedures and their substrate and inhibitor properties with
      purified E. coli purine nucleoside phosphorylase were examined. In agreement with
      previous findings, substrate activity was not detected for any of the compounds
      tested. Most of the nucleosides showed weak inhibition in the preliminary
      screening, i.e. at a concentration of about 100 microM. However some combinations
      of 6-chloro, 6-amino or 6-methoxy substituents with bulky hydrophobic groups at
      position 7 of the base and/or chloro, amino, methoxy or methylthio group at
      position 2 markedly enhanced affinity of such modified nucleosides for the E.
      coli enzyme. The most potent inhibition was observed for two nucleosides: 6
      chloro- and 2-amino-6-chloro-7-deazapurine 2'-deoxyribofuranosides that show
      inhibition constants Ki = 2.4 and 2.3 microM, respectively. Several other
      compounds were also found to be good inhibitors, with inhibition constants in the
      range 5-50 microM. In all instances the inhibition was competitive vs. the
      nucleoside substrate 7-methylguanosine. Inhibition constants for 7-deazapurine
      nucleosides are in general several-fold lower than those observed for their
      purine counterparts. Therefore 7-deaza modification together with substitutions
      at positions 2, 6 and 7 of the base is a very promising approach to obtain
      competitive noncleavable inhibitors of E. coli PNP that may bind to the enzyme
      with inhibition constants in the microM range.

PMID- 9918503
TI  - Effect of protein kinase ck2 on topoisomerase I from plasmodia of the slime mold
      Physarum polycephalum.
AB  - Relaxing activity of Physarum topoisomerase I was increased by calf thymus
      protein kinase ck2, similarly as was the activity of mammalian topoisomerase I,
      despite a pronounced difference between amino-acid sequences of non-conserved
      domains of Physarum and mammalian enzymes. This feature of Physarum topoisomerase
      I was cancelled in nuclear extracts isolated from dibutyryl-cAMP treated
      plasmodia in which the activity of protein kinase ck2 was elevated.

PMID- 9918504
TI  - Amino-acid composition of pyruvate kinase M2 isoenzyme variants from rat liver
      and Morris hepatoma 7777.
AB  - Cytosolic fractions B (salted out between 51-70% ammonium sulphate saturation)
      from rat liver and Morris hepatoma 7777, containing pyruvate kinase (EC 2.7.1.40)
      M2 isoenzymes, were purified by affinity chromatography on Blue Sepharose CL-6B.
      When compared by polyacrylamide gel electrophoresis at pH 8.3, all three M2
      pyruvate kinase variants from Morris hepatoma 7777 had lower mobilities (alpha2,
      beta2, gamma3) than the three corresponding variants (alpha1, beta1, gamma2) from
      normal rat liver. Using an automatic amino-acid analyser, significant differences
      in selected amino-acid content have been found in corresponding highly purified
      gamma3 and gamma2 variants from Morris hepatoma and normal rat liver,
      respectively. The gamma3-variant of the Morris hepatoma M2 isoenzyme had twice
      the amount of L-tyrosine and L-cysteine, and a content of L-serine higher by 20%
      than the corresponding gamma2 variant of the normal rat liver M2 isoenzyme. It
      contained, however, significantly less dicarboxylic amino acids which explains
      its lower electrophoretic mobility. It showed also a decrease (by about 10%) in
      several other amino-acid content, corresponding to a 10% decrease in the tumour
      enzyme molecular mass.

PMID- 9918505
TI  - Immunofluorescent detection of CD15-fucosylated glycoconjugates in primary
      cerebellar cultures and their function in glial-neuronal adhesion in the central
      nervous system.
AB  - Expression of CD15 antigen (also referred to as stage specific embryonic antigen,
      SSEA-1, or Lewis(x)) was analyzed in cerebellar cultures prepared from seven day
      old rats by double immunostaining with anti-CD15 mAb7A and cell-specific
      antibodies to glial fibrillary acidic protein (GFAP) and Vimentin. The
      immunocytochemical data suggest that the expression of CD15 antigen is restricted
      to some GFAP-positive cells with fibroblast-like morphology characteristic of
      Type-1 astrocytes. In order to explore the involvement of CD15 antigen in glial
      neuronal interactions, the ability of mAb7A antibody to interfere with granule
      cell adhesion to a monolayer of astrocytes was tested in comparison with anti
      GFAP. The adhesion of cerebellar granule cells to astrocytes, as determined by
      the number of bound cells, was decreased by 39% following preincubation with
      mAb7A. Anti-GFAP did not alter cell adhesion, indicating the specificity of the
      anti-CD15 antibody effect. These results are consistent with the hypothesis that
      CD15 antigen participates in glial-neuronal interactions in the developing
      cerebellum. Furthermore, it may be speculated that the modulation of cell-surface
      CD15 expression contributes to the altered strength of glial-neuronal
      interaction, facilitating cell migration and differentiation.

PMID- 9918506
TI  - Age-related profile of beta-N-acetylhexosaminidase glycosylation in rat liver.
AB  - Beta-N-acetylhexosaminidase was prepared from a liver lysosomal fraction obtained
      from rats between 18 days of gestation (group I) and 72 weeks of age (groups II
      VI). A glycan chain analysis was performed after an electrophoresis and blotting,
      followed by a very sensitive detection system with highly specific digoxigenin
      labelled lectins. The presence of high-mannose/hybrid type glycans, as well as
      their fucosylated forms was shown in all the experimental groups. Complex-type
      glycans with terminal sialic acid or galactose were present in all the groups
      except for 1-week-old rats in which only a positive reaction with lectins from
      Galanthus nivalis and Aleuria aurantia was observed. Thus it may be assumed that
      age-related changes in the glycosylation pattern occur on the first days after
      birth.

PMID- 9918507
TI  - The V3 region of gp120 is responsible for anti-HIV-1 activity of heparin
      sulphate.
AB  - The effect of heparin sulphate on the infection of CD4+ lymphocytes by
      recombinant HIV-1 clones pIIIB and by pIIIB/V3-BaL was investigated. It was
      demonstrated that heparin sulphate decreased the infectivity of CD4+ lymphocytes
      by the pIIIB virus stronger than by the pIIIB/V3-BaL clone, and that the effect
      of heparin was concentration-dependent. This was accompanied by an inhibition of
      binding of the monoclonal antibodies 447-52-D to the V3 region and G45-60 to the
      C4 region of oligomeric glycoprotein 120 (gp120). It has been concluded that the
      inhibitory effect of heparin sulphate on the infection of CD4+ lymphocytes by
      recombinant HIV-1 clones is mediated mainly by the V3 region of gp120. However,
      the C4 region contributes to the inhibitory effect of heparin sulphate.

PMID- 9918508
TI  - Electrophoretic and chromatographic patterns of glycosaminoglycans of the
      umbilical cord vessels and their alteration in EPH-gestosis.
AB  - It was found that hyaluronic acid is the most abundant glycosaminoglycan (GAG)
      both in the umbilical cord arteries and in the umbilical cord veins.
      Chromatographic and as well as electrophoretic studies demonstrated that EPH
      gestosis (Edema-Proteinuria-Hypertension), the most common pathological syndrome
      occurring in pregnancy, is accompanied by premature replacement of hyaluronic
      acid by sulphated GAGs in the investigated arteries but not in the veins. Such a
      replacement is a characteristic feature of the ageing process. One may conclude
      that EPH-gestosis is associated with a "premature ageing" of the umbilical cord
      arterial walls. The mechanism and possible role of this phenomenon in pathology
      are discussed.

PMID- 9918509
TI  - The diversity of polyprenol pattern in leaves of fruit trees belonging to
      Rosaceae and Cornaceae.
AB  - The polyprenol pattern in leaves of fruit trees belonging to the Rosaceae
      (genera: Prunus, Malus) and Cornaceae (genus: Cornus) families is presented. The
      content of polyprenyl acetates varied within plant species between 10-50 mg per
      gram of dry weight. In genus Prunus, Cornus and in representatives of species
      Malus domestica, a mixture of polyprenols composed of 18, 19, 20, 21 isoprene
      units was found. In six species of genus Prunus (sour-cherry): P. serrulata
      spontanea, P. yedoensis, P. fruticosa. P. kurilensis, P. subhirtella and P.
      incisa the presence of a second polyprenol family, i.e. the group of prenologues
      consisting of prenol -35, -36, -37, etc. up to -42 was detected.

PMID- 9918510
TI  - The effect of inorganic pyrophosphate on the transport of oleanolic acid
      monoglycosides into vacuoles isolated from Calendula officinalis leaves.
AB  - The influence of exogenous inorganic pyrophosphate on the transport of oleanolic
      acid monoglucoside and monoglucuronide to vacuoles isolated from Calendula
      officinalis leaf protoplasts was studied. The results indicate that the transport
      of both monoglycosides is carrier-mediated; however, the transport of the
      monoglucuronide is passive, and that of the monoglucoside active. The active
      transport of the monoglucoside is dependent on tonoplast energization created as
      a result of cooperation of two vacuolar proton pumps: H+-ATPase and H+-PPase.

PMID- 9918511
TI  - Importance of glutamate dehydrogenase stimulation for glucose and glutamine
      synthesis in rabbit renal tubules incubated with various amino acids.
AB  - The effect of 2-aminobicyclo[2.2.1]heptan-2-carboxylic acid (BCH), an L-leucine
      nonmetabolizable analogue and an allosteric activator of glutamate dehydrogenase,
      on glucose and glutamine synthesis was studied in rabbit renal tubules incubated
      with alanine, aspartate or proline in the presence of glycerol and octanoate,
      i.e. under conditions of efficient glucose formation. With
      alanine+glycerol+octanoate the addition of BCH resulted in a stimulation of
      alanine and glycerol consumption, accompanied by an increased glucose, lactate
      and glutamine synthesis. In contrast, when alanine was substituted by either
      aspartate or proline, BCH altered neither glucose formation nor glutamine and
      glutamate synthesis, while an accelerated glycerol utilization was accompanied by
      a small increase in lactate production. In view of the BCH-induced changes in
      intracellular metabolite levels the acceleration of gluconeogenesis by BCH in the
      presence of alanine+glycerol+octanoate is probably due to (i) increased uptake of
      alanine via alanine aminotransferase, (ii) stimulation of phosphoenolpyruvate
      carboxykinase, a key-enzyme of gluconeogenesis, (iii) rise of glucose-6
      phosphatase activity, as well as (iv) activation of the malate-aspartate shuttle
      resulting in an augmented glycerol utilization for lactate and glucose synthesis.

PMID- 9918512
TI  - The incorporation of various porphyrins into blood cells measured via flow
      cytometry, absorption and emission spectroscopy.
AB  - The incorporation of the five following porphyrins: meso-tetra(4-phenyl)porphyrin
      (TPP); meso-tetra(4-sulfonato-phenyl)porphyrin (TPPS4); meso-tetra(4
      naphthyl)porphyrin (TNP); tri-sulfo-tetra-phenyl porphyrin (TPPS3) and tetra
      sulfonato-naphthyl porphyrin (TNPS4) into human blood cells was investigated
      using flow cytometry, and absorption and emission spectroscopy. The percentage of
      stained cells, measured in a fluorescence cytometer, provided information on the
      efficiency of incorporation of fluorescent dye molecules into different types of
      cells. The yield of the incorporation of a dye was dependent on the type of dye
      and the solvent used for cell incubation. The degree of dye aggregation and
      ionization varied with the incubation medium, but dye molecules incorporated into
      cells seemed to be restricted to those in the monomeric state, exhibiting similar
      fluorescence yield. Of the three sulfonated porphyrins investigated only TPPS4
      was efficiently incorporated into leukocytes. In the incubation solvent, this dye
      was in monomeric and neutral form. TPPS3 which was also in monomeric form,
      practically was not incorporated into cells. TPP and TNP dissolved in 5% aqueous
      dimethyl sulfoxide were present mostly in aggregated forms but they penetrated
      the cells with a high efficiency.

PMID- 9918513
TI  - Nucleolin: a multifunctional major nucleolar phosphoprotein.
AB  - Nucleolin is a major protein of exponentially growing eukaryotic cells where it
      is present in abundance at the heart of the nucleolus. It is highly conserved
      during evolution. Nucleolin contains a specific bipartite nuclear localization
      signal sequence and possesses a number of unusual structural features. It has
      unique tripartite structure and each domain performs a specific function by
      interacting with DNA or RNA or proteins. Nucleolin exhibits intrinsic self
      cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities.
      Nucleolin also acts as a sequence-specific RNA binding protein, an autoantigen,
      and as the component of a B cell specific transcription factor. Its
      phosphorylation by cdc2, CK2, and PKC-zeta modulate some of its activities. This
      multifunctional protein has been implicated to be involved directly or indirectly
      in many metabolic processes such as ribosome biogenesis (which includes rDNA
      transcription, pre-rRNA synthesis, rRNA processing, ribosomal assembly and
      maturation), cytokinesis, nucleogenesis, cell proliferation and growth,
      cytoplasmic-nucleolar transport of ribosomal components, transcriptional
      repression, replication, signal transduction, inducing chromatin decondensation
      and many more (see text). In plants it is developmentally, cell-cycle, and light
      regulated. The regulation of all these functions of a single protein seems to be
      a challenging puzzle.

PMID- 9918514
TI  - Reappraisal of the role of heat shock proteins as regulators of steroid receptor
      activity.
AB  - Almost 30 years have passed since the original demonstration that steroid
      receptors, comprising a subfamily of the nuclear receptor (NR) superfamily, exist
      as large (6-8S) non-DNA-binding complexes in hypotonic extracts (cytosol) of
      target cells; later such complexes were shown to correspond to a heterooligomer
      composed of receptor, heat shock (Hsp), and other proteins. Subsequently, an
      impressive number of studies have dealt with the composition of the "nonactive"
      complex, its dissociation and/or reassembly in vitro, possible functions of the
      non-receptor components, and their subcellular compartmentalization. While there
      is little dispute about the chaperoning role of some Hsps in such a complex,
      there is still no final proof of an association in vivo of NRs and Hsps in the
      nuclei of target cells, which is requisite for a direct regulatory involvement of
      Hsps in NR function. Here we critically review the various models that have been
      put forward to attribute a biological function to the NR-Hsp90 interaction,
      evaluate the corresponding experimental data, and integrate recent concepts
      originating from the structural and functional analyses of NRs.

PMID- 9918515
TI  - Field of needs: the genetics of stroke.

PMID- 9918516
TI  - Beta-protein kinase C and hypertrophic signaling in human heart failure.

PMID- 9918517
TI  - Timing of surgery for patients with nonischemic severe mitral regurgitation.

PMID- 9918518
TI  - Prospective evaluation of the angiotensin-converting enzyme insertion/deletion
      polymorphism and the risk of stroke.
AB  - BACKGROUND: The D/I polymorphism of the ACE gene has been studied in relation to
      a variety of cardiovascular disorders, including stroke. A number of small
      studies have been conducted, with inconsistent results. We investigated the
      association between ACE genotype and the incidence of stroke in a large,
      prospective, matched case-control sample from the Physicians' Health Study.
      METHODS AND RESULTS: In the Physicians' Health Study, 348 subjects who had been
      apparently healthy at enrollment suffered a stroke during 12 years of follow-up,
      as determined from medical records and autopsy. A total of 348 cases were matched
      by age, time of randomization, and smoking habit to an equal number of controls
      (who had remained free of stroke). The D/I polymorphism was determined by
      polymerase chain reaction. Data were analyzed for the entire nested case-control
      sample, and also among a subgroup without a history of hypertension or diabetes
      mellitus, considered to be at low conventional risk (207 cases and 280 controls).
      All observed genotype frequencies were in Hardy-Weinberg equilibrium. The
      relative risk associated with the D allele was 1.11 (95% CI, 0.90 to 1.37;
      P=0.35), assuming an additive model in the matched analysis. Additional analyses
      assuming dominant or recessive effects of the D allele, as well as the analysis
      after stratification for low-risk status, showed no material as a statistically
      significant association. CONCLUSIONS: The results of this large, prospective
      study indicate that the ACE D/I gene polymorphism is not associated with
      subsequent risk of stroke.

PMID- 9918519
TI  - Changes in left ventricular diastolic function 6 months after nonsurgical septal
      reduction therapy for hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Nonsurgical septal reduction therapy (NSRT) decreases left
      ventricular outflow tract (LVOT) gradient and improves symptoms in patients with
      hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left
      ventricular diastolic function are currently unknown. METHODS AND RESULTS: HOCM
      patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT
      to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral
      annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant
      reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was
      accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178
      seconds; P=0.04) and New York Health Association class (from III to I; P<0.001).
      Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms;
      P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end
      diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS: NSRT
      improves LV relaxation and compliance, which contributes to the symptomatic
      relief seen at 6 months.

PMID- 9918520
TI  - Shed membrane microparticles with procoagulant potential in human atherosclerotic
      plaques: a role for apoptosis in plaque thrombogenicity.
AB  - BACKGROUND: The specific role of apoptosis in human atherosclerosis remains
      unknown. During apoptotic cell death, phosphatidylserine exposure on the cell
      surface confers a high tissue-factor (TF)-dependent procoagulant activity.
      METHODS AND RESULTS: In this study, we examined the role of apoptotic cell death
      in the promotion of plaque thrombogenicity. TF expression and its relation to
      apoptosis was analyzed in 16 human atherosclerotic plaques by the use of
      immunohistochemical techniques. The presence of shed membrane apoptotic
      microparticles was analyzed in extracts from 6 human atherosclerotic plaques and
      3 underlying arterial walls. The microparticles were captured by annexin V and
      their amounts estimated with respect to their phospholipid content by use of a
      prothrombinase assay. The prothrombogenic potential of the microparticles was
      further assessed by the measurement of total and microparticle-dependent TF
      activity in the extracts. The cell origin of the microparticles was determined
      after capture by specific antibodies. We were able to detect marked TF expression
      in the plaques in close proximity to apoptotic cells and debris, suggesting a
      potential interaction between TF and the apoptotic cell surfaces. High levels of
      shed membrane apoptotic microparticles were detected in extracts from
      atherosclerotic plaques but not in the underlying arterial walls (29.5+/-3.7
      nmol/L phosphatidylserine equivalent versus 1.3+/-0.4 nmol/L, respectively,
      P<0.02). The microparticles were mainly of monocytic and lymphocytic origin and
      retained 97+/-2% of total TF activity, indicating a direct causal relationship
      between shed membrane microparticles and procoagulant activity of plaque
      extracts. CONCLUSIONS: These results indicate that shed membrane microparticles
      with procoagulant potential are produced in human atherosclerotic plaques.
      Apoptosis could be a critical determinant of plaque thrombogenicity after plaque
      rupture.

PMID- 9918521
TI  - Vascular effects of estrogen and cholesterol-lowering therapies in
      hypercholesterolemic postmenopausal women.
AB  - BACKGROUND: Lipoproteins affect endothelium-dependent vasomotor responsiveness.
      Because lipoprotein effects of estrogen and cholesterol-lowering therapies
      differ, we studied the vascular responses to these therapies in
      hypercholesterolemic postmenopausal women. METHODS AND RESULTS: We randomly
      assigned 28 women to conjugated equine estrogen (CE) 0.625 mg, simvastatin 10 mg,
      and their combination daily for 6 weeks. Compared with respective baseline
      values, simvastatin alone and combined with CE reduced LDL cholesterol to a
      greater extent than CE alone (both P<0.05). CE alone and combined with
      simvastatin raised HDL cholesterol and lowered lipoprotein(a) to a greater extent
      than simvastatin alone (all P<0.05). Flow-mediated dilation of the brachial
      artery (by ultrasonography) improved (all P<0.001 versus baseline values) on CE
      (4.0+/-2.6% to 10.2+/-3.9%), simvastatin (4.3+/-2.4% to 10.0+/-3.9%), and CE
      combined with simvastatin (4.6+/-2.0% to 9.8+/-2.6%), but similarly among
      therapies (P=0.507 by ANOVA). None of the therapies improved the dilator response
      to nitroglycerin (all P>/=0.184). Only therapies including CE lowered levels of
      plasminogen activator inhibitor type 1 and the cell adhesion molecule E-selectin
      (all P<0. 05 versus simvastatin). CONCLUSIONS: Although estrogen and statin
      therapies have differing effects on lipoprotein levels, specific improvement in
      endothelium-dependent vasodilator responsiveness is similar. However, only
      therapies including estrogen improved markers of fibrinolysis and vascular
      inflammation. Thus, estrogen therapy appears to have unique properties that may
      benefit the vasculature of hypercholesterolemic postmenopausal women, even if
      they are already on cholesterol-lowering therapy.

PMID- 9918522
TI  - Association between myocardial infarction and the mast cells in the adventitia of
      the infarct-related coronary artery.
AB  - BACKGROUND: Histamine, a product of mast cells, is an effective vasoconstrictor
      of atherosclerotic coronary arteries. Because it has been suggested that coronary
      spasm plays a role in acute coronary syndromes such as myocardial infarction
      (MI), we quantified and characterized the mast cells in the adventitia of infarct
      related coronary arteries. METHODS AND RESULTS: In a series of 17 autopsied MI
      patients, we identified the segment of the left coronary artery with ruptured
      plaque responsible for the infarction. More distal segments from the infarct
      related coronary artery, either with nonruptured plaques or with normal intima,
      were also studied. Corresponding segments taken from left coronary arteries
      obtained from 17 patients who had died of noncardiac causes served as controls.
      Adventitial mast cells in the infarct-related and the control coronary arteries
      were identified immunohistochemically by staining for tryptase. In the infarct
      related coronary arteries, we also stained for chymase and histamine. Moreover, T
      lymphocytes and macrophages were identified immunohistochemically and counted. In
      the infarct-related coronary arteries, significantly larger numbers of mast cells
      were present in the adventitia backing ruptured plaques (98+/-40 mast cells/mm2,
      mean+/-SD) than in the adventitia backing nonruptured plaques (41+/-12 mast
      cells/mm2; P<0.001) or backing normal intima (19+/-8 mast cells/mm2; P<0.001). No
      such difference was found among the 3 different segments in the control coronary
      arteries. The majority of mast cells contained not only tryptase but also
      chymase. Mast cells were the only cells in the coronary adventitia that contained
      histamine. The proportion of adventitial mast cells that were degranulated was
      highest in the segments with ruptured plaques. The numbers of adventitial
      macrophages and T lymphocytes were also increased in the segments with plaque
      rupture. CONCLUSIONS: In infarct-related coronary arteries, the number of
      degranulated mast cells in the adventitia backing ruptured plaques is increased.
      Histamine released from the degranulated mast cells may reach the media, where it
      may locally provoke coronary spasm and thus contribute to the onset of MI.

PMID- 9918523
TI  - Effects of stroke on medical resource use and costs in acute myocardial
      infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries Study.
AB  - BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in
      approximately 30 000 US patients each year. This number is expected to rise with
      the increasing use of thrombolytic therapy for MI. However, no data exist for the
      economic effect of stroke in the setting of acute MI (AMI). The purpose of this
      prospective study was to assess the effect of stroke on medical resource use and
      costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource
      use and cost data were prospectively collected for 2566 randomly selected US
      GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who
      developed non-bypass surgery-related stroke during the baseline hospitalization.
      Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the
      baseline hospitalization, stroke was associated with a reduction in cardiac
      procedure rates and an increase in length of stay, despite a hospital mortality
      rate of 37%. Together with stroke-related procedural costs of $2220 per patient,
      the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001).
      Follow-up medical costs were substantially higher for stroke survivors ($22 400
      versus $5282, P<0.0001), dominated by the cost of institutional care. The main
      determinant for institutional care was discharge disability status. The
      cumulative 1-year medical costs for stroke patients were $15 092 higher than for
      no-stroke patients. Hemorrhagic stroke patients had a much higher hospital
      mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001),
      which was associated with approximately $7200 lower mean baseline hospitalization
      cost. At discharge, hemorrhagic stroke patients were more likely to be disabled
      (68% versus 46%, P=0.002). CONCLUSIONS: In this first large prospective economic
      study of stroke in AMI patients, we found that strokes were associated with a 60%
      ($15 092) increase in cumulative 1-year medical costs. Baseline hospitalization
      costs were 44% higher because of longer mean lengths of stay. Stroke type was a
      key determinant of baseline cost. Follow-up costs were more than quadrupled for
      stroke survivors because of the need for institutional care. Disability level was
      the main determinant of institutional care and thus of follow-up costs.

PMID- 9918524
TI  - Reporting risks and benefits of therapy by use of the concepts of unqualified
      success and unmitigated failure: applications to highly cited trials in
      cardiovascular medicine.
AB  - BACKGROUND: The NNT (number needed to treat) and NNH (number needed to harm) are
      useful in conveying the results of clinical trials because they emphasize the
      effort that must be expended to accomplish a single, tangible outcome. But NNT
      conveys the effort required to achieve a positive outcome without distinguishing
      between the presence or absence of treatment-related adverse events. Similarly,
      NNH conveys harm without accounting for the achievement or lack of achievement of
      the benefit of therapy. Consequently, a mathematical model was developed to
      extend the NNT and NNH to represent the effort required to achieve "unqualified
      success" (NNTUS, treatment success without treatment-induced side effects) and
      "unmitigated failure" (NNHUF, lack of treatment success with treatment-induced
      side effects). METHODS AND RESULTS: NNTUS was calculated by adjusting the
      absolute risk reduction to allow for the probability of not incurring a treatment
      related adverse event. NNHUF was similarly calculated by adjusting the absolute
      risk of incurring a treatment-related adverse event by the probability of not
      incurring any treatment-related benefit. The impact of conveying clinical trial
      data by the use of NNT, NNTUS, NNH, and NNHUF is illustrated by means of 11
      highly cited trials identified systematically from the cardiovascular literature.
      The treatment effort measured by the NNTUS and the NNHUF was consistently higher
      than that given by the traditional NNT and NNH. These increments ranged from 1%
      to several hundred percent. CONCLUSIONS: The NNTUS and the NNHUF represent the
      treatment effort required on average to achieve 1 unqualified success and 1
      unmitigated failure. NNTUS and NNHUF balance benefit and harm in an objective way
      and are relevant for making service delivery decisions.

PMID- 9918525
TI  - Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in
      the failing human heart.
AB  - BACKGROUND: Increased expression of Ca2+-sensitive protein kinase C (PKC)
      isoforms may be important markers of heart failure. Our aim was to determine the
      relative expression of PKC-beta1, -beta2, and -alpha in failed and nonfailed
      myocardium. METHODS AND RESULTS: Explanted hearts of patients in whom dilated
      cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC
      isoform content by Western blot, immunohistochemistry, enzymatic activity, and in
      situ hybridization and compared with nonfailed left ventricle. Quantitative
      immunoblotting revealed significant increases of >40% in PKC-beta1 (P<0.05) and 
      beta2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC
      alpha expression was significantly elevated by 70% in membrane fractions
      (P<0.03). PKC-epsilon expression was not significantly changed. In failed left
      ventricle, PKC-beta1 and -beta2 immunostaining was intense throughout myocytes,
      compared with slight, scattered staining in nonfailed myocytes. PKC-alpha
      immunostaining was also more evident in cardiomyocytes from failed hearts with
      staining primarily localized to intercalated disks. In situ hybridization
      revealed increased PKC-beta1 and -beta2 mRNA expression in cardiomyocytes of
      failed heart tissue. PKC activity was significantly increased in membrane
      fractions from failed hearts compared with nonfailed (1021+/-189 versus 261+/-89
      pmol. mg-1. min-1, P<0.01). LY333531, a selective PKC-beta inhibitor,
      significantly decreased PKC activity in membrane fractions from failed hearts by
      209 pmol. min-1. mg-1 (versus 42.5 pmol. min-1. mg-1 in nonfailed, P<0.04),
      indicating a greater contribution of PKC-beta to total PKC activity in failed
      hearts. CONCLUSIONS: In failed human heart, PKC-beta1 and -beta2 expression and
      contribution to total PKC activity are significantly increased. This may signal a
      role for Ca2+-sensitive PKC isoforms in cardiac mechanisms involved in heart
      failure.

PMID- 9918526
TI  - Role of extracellular signal-regulated kinases in angiotensin II-stimulated
      contraction of smooth muscle cells from human resistance arteries.
AB  - BACKGROUND: We assessed the role of extracellular signal-regulated kinases (ERKs)
      in Ang II-stimulated contraction and associated signaling pathways in vascular
      smooth muscle cells (VSMCs) from human small arteries. METHODS AND RESULTS: VSMCs
      derived from resistance arteries (<300 microm in diameter) from subcutaneous
      gluteal biopsies of healthy subjects (n=8) were used to assess Ang II-stimulated
      [Ca2+]i, pHi, and contractile responses. [Ca2+]i and pHi were measured with fura
      2-AM and BCECF-AM, respectively, and contraction was measured
      photomicroscopically in cells grown on Matrigel matrix. To determine whether
      tyrosine kinases and ERKs influence Ang II-stimulated responses, cells were
      pretreated with 10(-5) mol/L tyrphostin A-23 (tyrosine kinase inhibitor) and
      PD98059 (MEK inhibitor). Ang II-stimulated MEK activity was determined by
      tyrosine phosphorylation of ERKs. The angiotensin receptor subtypes (AT1 and AT2)
      were assessed with [Sar1,Ile8]Ang II (a nonselective subtype antagonist),
      losartan (a selective AT1 antagonist), and PD123319 (a selective AT2 antagonist).
      Ang II dose-dependently increased [Ca2+]i (pD2=8.4+/-0.36, Emax=541+/-55 nmol/L),
      pHi (pD2=9. 4+/-0.29, Emax=7.19+/-0.01), and contraction (pD2=9.2+/-0.21,
      Emax=36+/-2.2%). Ang II induced rapid tyrosine phosphorylation of ERKs, which was
      inhibited by PD98059. Tyrphostin A-23 and PD98059 attenuated (P<0.05) Ang II
      stimulated second messengers, and PD98059 reduced Ang II-induced contraction by
      >50%. [Sar1,Ile8]Ang II and losartan, but not PD123319, blocked Ang II-stimulated
      responses. CONCLUSIONS: These data demonstrate that in VSMCs from human
      peripheral resistance arteries, functional Ang II receptors of the AT1 subtype
      are coupled to signaling cascades involving Ca2+ and pHi pathways that are
      partially dependent on tyrosine kinases and ERKs. ERKs, the signaling cascades
      characteristically associated with cell growth, may play an important role in Ang
      II-stimulated contraction of human VSMCs.

PMID- 9918527
TI  - Impact of preoperative symptoms on survival after surgical correction of organic
      mitral regurgitation: rationale for optimizing surgical indications.
AB  - BACKGROUND: Surgical correction of mitral regurgitation in patients with no or
      mild symptoms remains controversial, particularly because the impact of
      preoperative symptoms on postoperative outcome is unknown. METHODS AND RESULTS:
      The long-term outcome of 478 patients with organic mitral regurgitation (199 in
      NYHA functional class I/II and 279 in class III/IV before surgery) operated on
      between 1984 and 1991 was analyzed. In patients in NYHA class I/II before surgery
      compared with those in class III/IV, postoperative long-term survival was higher
      (at 10 years, 76+/-5% versus 48+/-4%, P<0.0001), with lower operative mortality
      (0.5% versus 5.4%, P=0.003) and better late survival (P<0.0001). Comparison of
      observed and expected survival showed identical curves in patients in class I/II
      before surgery (P=0.18), whereas excess mortality was observed in patients in
      class III/IV before surgery (P<0.0001). Excess mortality associated with severe
      symptoms was also confirmed in all subgroups (all P<0.003) and in multivariate
      analysis (P=0.0036; adjusted hazard ratio [95% CI], 1.81 [1.21 to 2.70]).
      CONCLUSIONS: In patients with organic mitral regurgitation, preoperative
      functional class III/IV symptoms are associated with excess short- and long-term
      postoperative mortality independently of all baseline characteristics. These data
      should lead to consideration of surgical correction of severe organic mitral
      regurgitation when no or minimal symptoms are present in patients at low
      operative risk, especially if repair is feasible.

PMID- 9918528
TI  - Use of an extended monitoring strategy in patients with problematic syncope.
      Reveal Investigators.
AB  - BACKGROUND: The conventional investigation of patients who present with syncope
      involves short-term ECG monitoring or provocative testing with head-up tilt and
      electrophysiological testing. A symptom-rhythm correlation is often difficult to
      obtain during spontaneous syncope because of its sporadic, infrequent, and
      unpredictable nature. METHODS AND RESULTS: We used a prolonged monitoring
      strategy to determine the cause of syncope in 85 patients (age, 59+/-18 years; 44
      men) with recurrent undiagnosed syncope with an implantable loop recorder capable
      of cardiac monitoring for up to 18 months. During a mean of 10.5+/-4.0 months of
      follow-up, symptoms recurred in 58 patients (68%) 71+/-79 days (2.3+/-2.6 months)
      after implantable loop recorder insertion. An arrhythmia was detected in 42% of
      patients who recorded a rhythm during recurrent symptoms, with bradycardia
      present in 18 and tachycardia in 3. Five of the 18 bradycardic patients and 2
      additional sinus rhythm patients received a clinical diagnosis of neurally
      mediated syncope. Patients who experienced presyncope were much less likely to
      record an arrhythmia during symptoms compared with recurrence of syncope (24%
      versus 70%, P=0.0005). There were no adverse events associated with recurrent
      symptoms, and there were no sudden deaths. Inability to freeze after an event
      occurred in 8 patients, and pocket infection occurred in 3. CONCLUSIONS: The
      strategy of prolonged monitoring is effective and safe in patients with
      problematic syncope.

PMID- 9918529
TI  - Monoamine- and histamine-synthesizing enzymes and neurotransmitters within
      neurons of adult human cardiac ganglia.
AB  - BACKGROUND: Cardiac ganglia were originally thought to contain only cholinergic
      neurons relaying parasympathetic information from preganglionic brain stem
      neurons to the heart. Accumulating evidence, however, suggests that cardiac
      ganglia contain a heterogeneous population of neurons that synthesize or respond
      to several different neurotransmitters and neuropeptides. Reports regarding
      monoamine and histamine synthesis and neurotransmission within cardiac ganglia,
      however, present conflicting information or are limited in number. Furthermore,
      very few studies have examined the neurochemistry of adult human cardiac ganglia.
      The purpose of this study was, therefore, to determine whether monoamine- and
      histamine-synthesizing enzymes and neurotransmitters exist within neurons of
      adult human cardiac ganglia. METHODS AND RESULTS: Human heart tissue containing
      cardiac ganglia was obtained during autopsies of patients without cardiovascular
      pathology. Avidin-biotin complex immunohistochemistry was used to demonstrate
      tyrosine hydroxylase, L-dopa decarboxylase, dopamine beta-hydroxylase,
      phenylethanolamine-N-methyltransferase, tryptophan hydroxylase, and histidine
      decarboxylase immunoreactivity within neurons of cardiac ganglia. Dopamine,
      norepinephrine, serotonin, and histamine immunoreactivity was also found in
      ganglionic neurons. Omission or preadsorption of primary antibodies from the
      antisera and subsequent incubation with cardiac ganglia abolished specific
      staining in all cases examined. CONCLUSIONS: Our results suggest that neurons
      within cardiac ganglia contain enzymes involved in the synthesis of monoamines
      and histamine and that they contain dopamine, norepinephrine, serotonin, and
      histamine immunoreactivity. Our findings suggest a putative role for monoamine
      and histamine neurotransmission within adult human cardiac ganglia. Additional,
      functional evidence will be necessary to evaluate what the physiological role of
      monoamines and histamine may be in neural control of the adult human heart.

PMID- 9918531
TI  - Regulation of CCAAT/Enhancer binding protein, interleukin-6, interleukin-6
      receptor, and gp130 expression during myocardial ischemia/reperfusion.
AB  - BACKGROUND: Interleukin (IL)-6 is elevated in myocardium after ischemia and
      reperfusion. The IL-6 promoter/enhancer region contains response elements for
      nuclear factor-kappaB, AP-1, and CCAAT/enhancer binding protein (C/EBP).
      Expression and regulation of C/EBP in rat myocardium after ischemia and
      reperfusion has not been defined, nor has the behavior of the specific IL-6
      receptor (IL-6R) or the signal transducer gp130. METHODS AND RESULTS: C/EBP DNA
      binding activity was not detected in shams or in previously ischemic tissue at 15
      minutes of reperfusion; it was detected at 30 minutes of reperfusion, increased
      at 1 hour of reperfusion, and declined by 6 hours of reperfusion. A supershift
      was observed with anti-C/EBP-beta but not with anti-alpha or anti-delta
      antibodies. mRNA and protein levels of IL-6 and gp130 were detected at low levels
      in controls, increased at 1 hour of reperfusion, and remained high until 6 hours
      of reperfusion. IL-6R mRNA and protein were not detected in controls, but its
      mRNA was induced at 1 hour of reperfusion and its protein at 2 hours of
      reperfusion. Although effects of reperfusion were rapid, in ischemic tissue not
      reperfused, low levels of C/EBP were detected at 4 hours, and at 24 hours the
      levels were slightly elevated. Significant upregulation in IL-6, IL-6R, and gp130
      occurred only at 24 hours of sustained ischemia. CONCLUSIONS: Reperfusion after a
      brief period of ischemia caused induction of myocardial C/EBP (beta-subunit). The
      rapid and sustained production of IL-6 with concomitant expression of IL-6
      receptor and gp130 suggest that these factors may participate in a local
      inflammatory cascade after myocardial ischemia and reperfusion.

PMID- 9918530
TI  - Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1
      expression in cholesterol-loaded human macrophages: relevance to stability of
      atherosclerotic plaque.
AB  - BACKGROUND: The accumulation of macrophage-derived foam cells in atherosclerotic
      lesions correlates with increased local release of matrix-degrading
      metalloproteinases (MMPs) and a thin fibrous cap. The activity of these enzymes
      is controlled by specific tissue inhibitors of metalloproteinases (TIMPs).
      METHODS AND RESULTS: Because oxidized low-density lipoprotein (OxLDL) modulates
      gene expression, we investigated the effect of these particles on the levels of
      MMP-1, MMP-3, MMP-9, TIMP-1, and TIMP-2 in the culture media of human monocyte
      derived macrophages. OxLDL but not native LDL or high-density lipoprotein reduced
      the level of TIMP-1 in a dose-dependent manner with maximal effect (60% of
      control) at approximately 100 microg protein/mL. In addition, Northern blotting
      revealed marked reduction in the abundance of TIMP-1 mRNA in OxLDL-treated cells.
      Evaluation of the effect of oxysterol components of OxLDL on TIMP-1 production
      revealed that 25-hydroxycholesterol (1 microg/mL) was the most potent inhibitor (
      approximately 30% of control). Such inhibition was partially mediated by
      interleukin (IL)-8. Indeed, IL-8 (2.5 ng/mL) induced maximal inhibition of TIMP-1
      accumulation (30% of control) in 4 of 6 cell preparations. In addition, the
      inhibitory effect of OxLDL-treated cells in the presence of an anti-IL-8
      neutralizing antibody was partially reversed. CONCLUSIONS: Immunohistochemical
      analyses of human atherosclerotic plaques revealed the expression of TIMP-1 in
      some but not all macrophage-rich and IL-8-rich areas. Therefore, IL-8 may play a
      potential atherogenic role by inhibiting local TIMP-1 expression, thereby leading
      to an imbalance between MMPs and TIMPs at focal sites in the atherosclerotic
      plaque.

PMID- 9918532
TI  - Amelioration by quinapril of myocardial infarction induced by coronary
      occlusion/reperfusion in a rabbit model of atherosclerosis: possible mechanisms.
AB  - BACKGROUND: The increased severity of the myocardial injury produced by coronary
      occlusion-reperfusion in models of atherosclerosis is associated with an increase
      in leukocyte accumulation in the ischemic myocardium. Expression of P-selectin,
      an adhesion molecule involved in the interaction between leukocytes and
      endothelium, is increased in atherosclerotic vessels. Long-term angiotensin
      converting enzyme (ACE) inhibition has been shown to reduce atherosclerotic
      vascular change in experimental models. METHODS AND RESULTS: We examined changes
      in the size of the infarct resulting from coronary occlusion/reperfusion in
      normally fed and cholesterol-fed rabbits that were chronically treated with
      quinapril. Infarct size was significantly larger in the cholesterol-fed versus
      normally fed rabbits. ACE activity in the ischemic and nonischemic myocardium was
      significantly reduced by quinapril. Chronic quinapril administration
      significantly ameliorated the increased myocardial injury in cholesterol-fed
      rabbits. Quinapril administration markedly increased the myocardial cGMP content
      and reduced the myeloperoxidase activity in the border region of the ischemic
      myocardium in cholesterol-fed rabbits. The enhanced expression of P-selectin in
      myocardial tissue of cholesterol-fed rabbits was also effectively reduced by
      quinapril treatment. The above effects of quinapril were eliminated by blockade
      of bradykinin B2 receptors or inhibition of nitric oxide synthesis. CONCLUSIONS:
      Chronic quinapril treatment ameliorated the severity of myocardial injury
      produced by coronary occlusion/reperfusion in cholesterol-fed rabbits, possibly
      because of reversal of the enhanced interaction between leukocytes and
      endothelium in the ischemic myocardium via a bradykinin-related pathway.

PMID- 9918533
TI  - RGS4 inhibits G-protein signaling in cardiomyocytes.
AB  - BACKGROUND: RGS family members are GTPase-activating proteins for heterotrimeric
      Gq and Gi proteins. RGS genes are expressed in heart tissue and in cultured
      cardiomyocytes. There is evidence that altered RGS gene expression may contribute
      to the pathogenesis of cardiac hypertrophy and failure. METHODS AND RESULTS: We
      investigated the ability of RGS proteins to block G-protein signaling in vivo by
      using a cultured cardiomyocyte transfection system. Endothelin-1, angiotensin II,
      and phenylephrine signal through Gq or Gi family members and promote the
      hypertrophy of cardiomyocytes. We found that phenylephrine-mediated and
      endothelin-1-mediated induction of the atrial natriuretic factor and myosin light
      chain-2 genes was inhibited in cells that were transfected with RGS4.
      Phenylephrine-mediated gene induction was not inhibited in cells that were
      transfected with N128A-RGS4, a point mutant form that lacks GTPase-activating
      protein activity. Phenylephrine-mediated myofilament organization and cell growth
      were also blocked in cells by RGS4. CONCLUSIONS: These results demonstrate that
      RGS protein can inhibit G-protein-mediated signaling in vivo and suggest that
      increased expression of RGS protein may be a counterregulatory mechanism to
      inhibit G protein signaling.

PMID- 9918534
TI  - Magnetic resonance imaging and invasive evaluation of development of heart
      failure in transgenic mice with myocardial expression of tumor necrosis factor
      alpha.
AB  - BACKGROUND: Transgenic mice expressing tumor necrosis factor-alpha (TNF-alpha) in
      cardiac myocytes develop dilated cardiomyopathy, but the temporal progression to
      cardiac dysfunction is not well characterized. We asked (1) Does magnetic
      resonance imaging (MRI) provide a reproducible assessment of cardiac output in
      mice that correlates with invasive measurements obtained with thermodilution? (2)
      What is the time course of left ventricular (LV) remodeling in transgenic mice
      with myocardial expression of TNF-alpha? METHODS AND RESULTS: Transgenic mice
      from 2 different lineages with differing amounts of myocardial TNF-alpha
      expression [lineage 1 (L1) and lineage 2 (L2)] and littermate controls (LC) were
      studied. In protocol 1, cardiac output (CO) and stroke volume (SV) were measured
      by MRI and thermodilution (TD) in 15 mice (3 L1, 4 L2, 8 LC). In protocol 2, 23
      mice (7 L1, 8 L2, 8 LC) were scanned at 1 month of life and every 4 weeks
      thereafter. In both protocols, cine-MRI was performed with the use of a 1.5-T
      clinical system (1.5-mm slices, 195x195 microm in-plane resolution). MRI CO and
      SV correlated well with TD [COTD (mL/min)=0.94*COMRI+0.72, r=0.84; SVTD(
      microL)=1. 01*SVMRI-1.07, r=0.94]. Serial MRI studies showed significant increase
      in LV mass and volumes over time and a significant decrease in ejection fraction
      in transgenic mice when compared with littermate controls. Compared with lineage
      2, lineage 1 showed significantly larger LV mass and volumes and significantly
      lower ejection fraction. CONCLUSIONS: MRI assessment of cardiac function in mice
      correlates well with invasive measurements. Serial MRI studies in the TNF-alpha
      mouse model demonstrate that the rate of progression and severity of LV
      dysfunction are dependent on the degree of TNF-alpha overexpression.

PMID- 9918535
TI  - Images in cardiovascular medicine. Isolated congenital absence of the pulmonary
      valve.

PMID- 9918536
TI  - Factor V Leiden, prothrombin 20210 gene variant, and risk of myocardial
      infarction.

PMID- 9918537
TI  - Progression from homologous to heterologous desensitization of contraction in
      gastric smooth muscle cells.
AB  - Acute desensitization of contraction and its relative mechanisms have been
      studied in smooth muscle cells isolated from guinea pig stomach. Desensitization
      was induced by pre-exposure of the cells to one of the excitatory neuropeptides
      linked to the phospholipase C intracellular cascade, i.e., cholecystokinin (CCK),
      gastrin-releasing peptide, and Substance P. Desensitization was homologous after
      a 30-s pre-exposure and heterologous if pre-exposure lasted for 5 min or longer.
      Homologous desensitization was studied in a more detailed way after pre-exposure
      to CCK. Preincubation with increasing concentrations of CCK (10 pM-1 microM)
      induced a progressive rightward shift of the dose-response curves associated with
      both a decrease in potency (ED50 4.5 pM-2.2 nM) and a maximum response that were
      not related to a modification of response kinetics. After brief pre-exposure to 1
      nM CCK (Dmax), an inhibition of contraction was observed in response to an
      identical dose of CCK (45.1 +/- 8.6%), the decreased response being associated
      with an inhibition of inositol phosphates and [Ca++]i mobilization. Both inositol
      trisphosphate (InsP3)-induced contraction and [Ca++]i mobilization were inhibited
      to a lesser extent than CCK-induced responses. Any longer pre-exposure of cells
      to one of the above-mentioned neuropeptides caused heterologous desensitization,
      with an observed inhibition of contraction in response to all tested agonists
      (CCK, 60.3 +/- 5.9%; gastrin-releasing peptide: 56.7 +/- 3. 5%; Substance P, 60.6
      +/- 6.5%). A similar decrease was observed in InsP3-induced contractions
      resulting in a desensitization of the InsP3 response as well. Full recovery of
      contractile responses appeared within 30 min from the end of preincubation, thus
      indicating that degradation of membrane receptors did not occur. Although pre
      exposure of the cells to protein kinase C inhibitor GF109203X did not modify CCK
      induced homologous desensitization, it blocked CCK-induced heterologous
      desensitization. This study demonstrates that excitatory phospholipase C-coupled
      enteric neuropeptides induce a time-dependent homologous as well as heterologous
      desensitization of smooth muscle contraction occurring at receptor and
      postreceptor levels.

PMID- 9918538
TI  - Characterization of pardaxin-induced dopamine release from pheochromocytoma
      cells: role of calcium and eicosanoids.
AB  - Pardaxin, an excitatory neurotoxin, induced dopamine release from
      pheochromocytoma (PC12) cells both in the presence and absence of extracellular
      calcium ([Ca]o). In the presence of extracellular calcium, nifedipine, an L-type
      calcium channel blocker, did not affect dopamine release, whereas 1,2-bis (2
      aminophenoxy) ethane N,N, N'N'-tetra-acetic acid (BAPTA), a chelator of cytosolic
      calcium, and dantrolene, a blocker of calcium release from intracellular stores,
      inhibited only partially (30-40%) pardaxin-induced dopamine release. In the
      absence of [Ca]o, BAPTA and dantrolene were ineffective. Pardaxin stimulated the
      arachidonic acid (AA) cascade in PC12 cells independently of [Ca]o. The
      phospholipase inhibitors mepacrine and bromophenacyl bromide inhibited both
      pardaxin-induced AA release and pardaxin-induced dopamine release. Dopamine
      release induced by pardaxin also was blocked by the lipoxygenase inhibitors
      nordihydroguaiaretic acid, esculetin, and 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6
      trimethyl-1,4-benzoquinone. Under these conditions, a parallel reduction in 5
      hydroxyeicosatetranoic acid release also was observed. Suppression of pardaxin
      induced dopamine release by inhibitors of phospholipase A2 and lipoxygenase was
      more pronounced in calcium-free medium. These results indicate the involvement of
      the lipoxygenase pathway in pardaxin-induced dopamine release and suggest the use
      of this toxin as a novel pharmacological tool for investigating the mechanism of
      calcium-independent neurotransmitter release.

PMID- 9918539
TI  - Endothelium-dependent and -independent mechanisms of vasorelaxation by
      corticotropin-releasing factor in pregnant rat uterine artery.
AB  - Corticotropin-releasing factor (CRF), a potent vasorelaxant, is increased
      tremendously during human pregnancy. Placenta is the main source for this
      increase. CRF is thought to be important in modulating vascular resistance and
      uteroplacental blood flow during pregnancy. Here we investigated pathways
      mediating a vasorelaxant effect of CRF in the uterine artery. Two-millimeter
      segments of uterine artery (o.d. 300-400 microm) from day 18 pregnant rats were
      mounted in a small vessel myograph and precontracted with norepinephrine, and
      relaxation responses to CRF were studied. CRF relaxed the uterine artery in a
      concentration-dependent manner. Relaxation of uterine artery by CRF was abolished
      completely by alpha-helical CRF 9-41 (CRF antagonist, 1 micromol) and partially
      by removal of endothelium, Nomega-nitro-L-arginine methyl ester (nitric oxide
      synthase inhibitor, 0.1 mmol), 6-anilino-5,8-quinolinedione (guanylate cyclase
      inhibitor, 10 micromol), or thiopental/miconazole (cytochrome P-450 inhibitors,
      0.3 mmol/30 micromol), but remained unaffected by indomethacin (cyclo-oxygenase
      inhibitor, 10 micromol). Relaxation was also inhibited when depolarizing solution
      (K+, 120 mmol) was used for precontraction. In deendothelized preparations,
      relaxation was not inhibited by 9-tetrahydro-2-furanyl-9H-purin-6-amine
      (adenylate cyclase inhibitor, 0.2 mmol), glibenclamide (adenosine triphosphate
      dependent K+ channel blocker, 10 micromol), tetrabutyl ammonium (nonspecific K+
      channel blocker, 1 mmol), nitrendipine (voltage-gated Ca++ channel blocker, 1
      micromol), or when vessels were precontracted with depolarizing solution. CRF
      causes vasorelaxation by receptor-operated, endothelium-dependent and 
      independent pathways. The endothelium-dependent relaxation is mediated by nitric
      oxide-cyclic guanosine monophosphate pathway and endothelium-derived
      hyperpolarizing factor but not prostacyclin. However, cyclic adenosine
      monophosphate, K+ channels, or Ca++ channels are not involved in endothelium
      independent vasorelaxation by CRF.

PMID- 9918540
TI  - Hepatic disposition of the acyl glucuronide1-O-gemfibrozil-beta-D-glucuronide:
      effects of dibromosulfophthalein on membrane transport and aglycone formation.
AB  - The liver plays an important role in the disposition of acyl glucuronides by
      determining their extent of formation, biliary excretion, and efflux into blood.
      Thus, both intrahepatic and extrahepatic exposure to these reactive polar
      conjugates depends on the efficiency of hepatic transport mechanisms, which may
      be shared with other nonbile acid organic anions. Using the isolated perfused rat
      liver preparation, the hepatic disposition of the acyl glucuronide, 1-O
      gemfibrozil-beta-D-glucuronide, was examined in the presence of the organic anion
      dibromosulfophthalein (DBSP). Using a recirculating system, livers were perfused
      for 90 min with an erythrocyte-free perfusion medium containing 1% (w/v) albumin
      and 1-O-gemfibrozil-beta-D-glucuronide (3 microM) alone (n = 6) or with DBSP (200
      microM, n = 7). The glucuronide was avidly taken up by the liver, excreted into
      bile, and hydrolyzed within the liver to its aglycone, gemfibrozil. DBSP
      significantly (P <.05) lowered the conjugate's mean hepatic clearance (8.98-5.17
      ml/min), intrinsic clearance (44.0-17.7 ml/min), and fraction eliminated in bile
      (72. 8-48.7% of the dose), while increasing perfusate gemfibrozil concentrations
      (0.52-0.92 microM at 90 min). Furthermore, DBSP significantly (P <.05) lowered
      the ratio of intrahepatic to unbound perfusate concentrations of 1-O-gemfibrozil
      beta-D-glucuronide (139. 0-35.0) and showed a trend to lower the ratio of bile to
      intrahepatic concentrations (111.3-76.2, P =.05). Thus, the study demonstrated
      that DBSP inhibited both the sinusoidal uptake and canalicular transport of 1-O
      gemfibrozil-beta-D-glucuronide, suggesting that the hepatic membrane transport of
      acyl glucuronides is carrier mediated and shared with other organic anions.

PMID- 9918541
TI  - CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates
      the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal
      dopaminergic neurons In vivo.
AB  - We have identified a bis-ethylthiomethyl analog of K-252a, CEP-1347/KT-7515, that
      promotes neuronal survival in culture and in vivo. The neuronal survival
      properties of CEP-1347/KT-7515 may be related to its ability to inhibit the
      activation of c-jun N-terminal kinase, a key kinase in some forms of stress
      induced neuronal death and perhaps apoptosis. There is evidence that the
      selective nigrostriatal dopaminergic neurotoxin, MPTP, produces neuronal
      apoptosis in culture and in adult mice. Thus, our studies were designed to
      determine if CEP-1347/KT-7515 could protect dopaminergic neurons from MPTP
      mediated neurotoxicity. CEP-1347/KT-7515 was assessed for neuroprotective
      activity in a low dose MPTP model (20 mg/kg) where there was a 50% loss of
      striatal dopaminergic terminals in the absence of substantia nigra neuronal loss,
      and a high dose (40 mg/kg) MPTP model where there was a complete loss of
      dopaminergic terminals and 80% loss of dopaminergic cell bodies. In the low dose
      MPTP model, CEP-1347/KT-7515 (0.3 mg/kg/day) attenuated the MPTP-mediated loss of
      striatal dopaminergic terminals by 50%. In the high dose model, CEP-1347/KT-7515
      ameliorated the loss of dopaminergic cell bodies by 50% and partially preserved
      striatal dopaminergic terminals. CEP-1347/KT-7515 did not inhibit monoamine
      oxidase B or the dopamine transporter, suggesting that the neuroprotective
      effects of CEP-1347/KT-7515 occur downstream of the metabolic conversion of MPTP
      to MPP+ and accumulation of MPP+ into dopaminergic neurons. These data implicate
      a c-jun N-terminal kinase signaling system in MPTP-mediated dopaminergic
      degeneration and suggest that CEP-1347/KT-7515 may have potential as a treatment
      for Parkinson's disease.

PMID- 9918542
TI  - Pharmacological inhibition of protein kinases in intact cells: antagonism of beta
      adrenergic receptor ligand binding by H-89 reveals limitations of usefulness.
AB  - The use of pharmacological inhibitors of protein kinases represents a potentially
      powerful tool in dissecting the regulatory features of intracellular signaling
      pathways. However, although the in vitro potency, selectivity, and efficacy of
      numerous kinase inhibitors have been characterized, little is known regarding the
      usefulness of these compounds as inhibitors in intact cells. In attempting to
      characterize the role of protein kinase A (PKA) in regulating the beta-2
      adrenergic receptor (AR) in human airway cells, we observed a seemingly profound
      capacity of the isoquinoline H-89, a potent and widely used PKA inhibitor, to
      attenuate agonist-mediated desensitization of the beta-2 AR. Although additional
      experiments identified H-89 as an effective inhibitor of intracellular PKA,
      extended analysis of the compound determined the principal effect of H-89 was via
      its action as a beta-2 AR antagonist. Pretreatment with or the acute addition of
      H-89 significantly attenuated isoproterenol-stimulated cAMP accumulation. In
      cells pretreated with H-89 and then washed extensively, the subsequent dose
      dependent response to isoproterenol suggested beta-2 AR antagonism by retained H
      89. Competition binding of [125I]iodopindolol established Ki values of
      approximately 180 nM and 350 nM for H-89 antagonism of beta-2 AR and beta-1 AR,
      respectively. Additional receptor binding studies suggest selectivity of H-89 for
      the beta-2 AR and beta-1 AR, although a weak antagonism (Ki values of
      approximately 10 microM or greater) of other G protein-coupled receptors was
      observed. Results from additional pharmacological and biochemical analyses of
      various protein kinase inhibitors further established the need for careful
      characterization of pharmacological inhibitors when used in intact cell models.

PMID- 9918543
TI  - Opioid receptor selectivity of heroin given intracerebroventricularly differs in
      six strains of inbred mice.
AB  - Heroin administered i.c.v. acts on supraspinal mu opioid receptors in ICR mice
      but on delta receptors in Swiss Webster mice. The purpose of this study was to
      determine the degree to which genotype plays a role in the opioid receptor
      selectivity of heroin across a range of fully inbred strains of mice. Six inbred
      strains were given heroin i.c.v. 10 min before the tail-flick test. Differences
      in the descending neurotransmitter systems involved in supraspinal opioid-induced
      analgesia were evaluated as the first step. Antagonism by bicuculline given
      intrathecally indicated the involvement of supraspinal delta receptors in
      activating spinal gamma-aminobutyric acid (GABA) receptors; antagonism by
      intrathecal methysergide indicated either mu or kappa receptor involvement.
      Antagonism by intrathecal yohimbine implicated mu and eliminated kappa receptor
      involvement. Intracerbroventricular opioid antagonists (beta-funaltrexamine, 7
      benzylidenenaltrexone, naltriben, or nor-binaltorphimine) provided further
      differentiation. Based on these initial results, receptor selectivity was
      determined by more extensive ED50 experiments with i.c.v. administration of
      heroin with opioid antagonists, beta-funaltrexamine (for mu), naltrindole (for
      delta), and nor-binaltorphimine (for kappa). The combined results indicated that
      heroin analgesia was predominantly mediated in C57BL/6J by delta, in DBA/2J and
      CBA/J by mu, and in BALB/cByJ and AKR/J by kappa receptors. The response in
      C3H/HeJ appeared to involve mu receptors. The results indicate that the opioid
      receptor selectivity of heroin is genotype-dependent. Because these genotypes are
      fully inbred, the genetically determined molecular and neurochemical substrate
      mediating the different opioid receptor selectivities of heroin can be studied
      further.

PMID- 9918544
TI  - Adenosine A1 receptor-dependent and -independent effects of the allosteric
      enhancer PD 81,723.
AB  - The 2-amino-3-benzoylthiophene PD 81,723 has been shown to exhibit allosteric
      enhancement of adenosine A1 receptor binding and function. The aim of this study
      was to clarify the mechanism of this effect using membranes purified from rat
      brain and Chinese hamster ovary (CHO)-A1 cells that stably express the rat
      adenosine A1 receptor as well as intact CHO-A1 and nontransfected CHO cells. In
      membranes containing 100 microM magnesium, (2-amino-4, 5-dimethyl-3-thienyl)-[3
      (trifluoromethyl)phenyl]methanone (PD 81, 723) significantly increased the
      affinity of the adenosine A1 receptor agonist, cyclopentyladenosine, for the low
      affinity receptor without affecting high-affinity binding or Bmax. In intact
      cells, PD 81,723 inhibited basal adenylyl cyclase (AC) activity as well as
      forskolin-, cholera toxin-, and pertussis toxin-stimulated AC activity in CHO-A1
      and CHO cells. Basal AC activity was inhibited 49% in CHO and 82% in CHO-A1 cells
      by 30 microM PD 81,723. In CHO-A1 cells, half-maximal inhibition of forskolin
      stimulated AC occurred at 5 microM PD 81,723 compared to 10 microM in CHO cells.
      Cholera toxin-stimulated AC was reduced 90% in both CHO and CHO-A1 cells by 30
      microM PD 81,723. At the same concentration of PD 81,723, pertussis toxin
      stimulated AC activity was reduced 86% (CHO-A1) and 77% (CHO). [3H]forskolin was
      displaced from purified rat liver AC by PD 81,723 with an IC50 of 96 microM.
      These results demonstrate that two mechanisms appear to contribute to the
      observed effects of PD 81, 723. One mechanism is allosteric enhancement of
      adenosine A1 receptor function. Results from transfected and nontransfected cells
      suggest that PD 81,723 also inhibits AC directly by binding to the catalytic unit
      at or near the forskolin-binding site.

PMID- 9918545
TI  - Ethanol counteraction of I1-imidazoline but not alpha-2 adrenergic receptor
      mediated reduction in vascular resistance in conscious spontaneously hypertensive
      rats.
AB  - Our recent findings have shown that ethanol selectively counteracts decreases in
      blood pressure (BP) evoked via activation of central I1-imidazoline receptors but
      not alpha-2 adrenoceptors in conscious spontaneously hypertensive rats (SHRs).
      This study investigated the role of sympathetic activity, cardiac output and
      total peripheral resistance (TPR) in the differential effect of ethanol on
      centrally mediated hypotension. Changes in plasma norepinephrine (NE), as index
      of sympathetic activity, BP, heart rate, cardiac index, stroke volume, and TPR
      elicited by rilmenidine or alpha-methylnorepinephrine (selective I1 and alpha-2
      receptor agonists, respectively) and subsequent ethanol (0.5 or 1 g/kg) or
      saline, were evaluated in conscious SHRs. Intracisternal rilmenidine (25 microg)
      or alpha-methylnorepinephrine (alpha-MNE; 4 microg) elicited similar decreases in
      BP, TPR, and plasma NE, but cardiac index was not changed. Ethanol (0.5 g/kg
      i.v.) had no effect on hemodynamic responses to rilmenidine or alpha-MNE. The
      higher dose (1 g/kg i.v.) of ethanol counteracted the hypotensive response to
      rilmenidine and significantly (P <.05) elevated TPR and plasma NE. In contrast,
      ethanol (1 g/kg) had no effect on the hypotensive responses to alpha-MNE but
      significantly (P <.05) elevated plasma NE. However, this increase in NE was
      approximately one third of the increase evoked by ethanol when given after
      rilmenidine. These findings suggest that the selective counteraction by ethanol
      of the hypotension evoked via activation of central I1 but not alpha-2 receptors
      may relate, at least in part, to its greater ability to reverse the
      sympathoinhibition and the associated decrease in vascular resistance mediated by
      I1 receptors.

PMID- 9918546
TI  - Biotransformation of coumarin by rodent and human cytochromes P-450: metabolic
      basis of tissue-selective toxicity in olfactory mucosa of rats and mice.
AB  - Coumarin was previously found to cause tissue-selective toxicity in the olfactory
      mucosa (OM) of rats and mice, with rats being the more sensitive species. The aim
      of this study was to explore the role of target tissue biotransformation in OM
      selective toxicity and the metabolic basis of the species differences in coumarin
      toxicity. At least six coumarin metabolites were detected in OM microsomal
      reactions, with o-hydroxyphenylacetaldehyde (o-HPA) being the most abundant.
      Formation of o-HPA was inhibited by reduced glutathione, confirming its origin
      from a reactive intermediate. There were significant differences in the rates and
      metabolite profiles of coumarin metabolism in the livers of Wistar rats and
      C57BL/6 mice. The rates of metabolic activation of coumarin, as indicated by the
      formation of o-HPA, were comparable in OM microsomes of the two species but about
      25- and 3-fold higher in OM than in liver microsomes of rats and mice,
      respectively. Thus, target tissue activation seems to play an important role in
      the tissue-selective toxicity, whereas differences in the rates of hepatic
      metabolism may be responsible for the species difference in olfactory toxicity.
      Purified, heterologously expressed mouse CYP2A5 and CYP2G1 produced 7
      hydroxycoumarin and o-HPA as the predominant products, respectively. Kinetic
      analysis and immunoinhibition studies indicated that the OM-specific CYP2G1 plays
      the major role in metabolic activation of coumarin. Furthermore, of 13 human
      cytochrome P-450s (P-450s) examined, five (CYP1A1, CYP1A2, CYP2B6, CYP2E1, and
      CYP3A4) were active in the metabolic activation of coumarin, suggesting a
      potential risk of coumarin toxicity in humans.

PMID- 9918547
TI  - Effects of polytherapy compared with monotherapy in antiepileptic drugs: an
      animal study.
AB  - Although monotherapy in epilepsy treatment is frequently advocated, this is not
      based on studies with equal drug loads. This study was performed to investigate
      the experimental background of polytherapy with standardized drug loads. Dose
      dependent effects on grip strength, accelerod performance, and spontaneous
      behavior of rats was used to study the effect of combining valproate and
      ethosuximide. The potency of the drugs (combination) was obtained by fitting the
      sigmoid Emax equation to the data. Drug interaction was assessed using the
      isobologram method and quantified by comparing equivalent drug loads with their
      95% confidence intervals. We found that the effects of valproate and ethosuximide
      combine in a simple additive way in the grip strength experiment as well as in
      the accelerod experiment. In the behavioral studies, however, a higher drug load
      of the combination was needed to obtain the same amount of sedation, signifying
      infra-additivity. Infra-additivity of sedative effects is an important finding
      because this is by far the most frequent side effect mentioned in human studies.
      However, assessment of the therapeutic effect of the combination will have to be
      completed before a preference for mono- or polytherapy, based on the balance of
      adverse effects and efficacy, can be expressed.

PMID- 9918548
TI  - Large receptor reserve for cannabinoid actions in the central nervous system.
AB  - The receptor occupancy required to produce cannabinoid effects in the central
      nervous system was determined in both a neurochemical and a behavioral assay for
      cannabinoid actions. In the neurochemical experiments, performed on superfused
      rat hippocampal slices, electrically evoked [3H]acetylcholine release was
      inhibited by the cannabinoid agonist, WIN 55212 to 2 with an EC50 of 0.005 microM
      and maximum effect of 79%. In parallel experiments examining binding of the
      radiolabeled CB1 antagonist [131I]AM 281 (N-(morpholin-4-yl)-5-(4
      [131I]iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) to
      living hippocampal slices, WIN 55212 to 2 inhibited [131I]AM 281 binding with an
      EC50 of 1.3 microM. From these two sets of data it was determined that 50% of
      maximal inhibition of [3H]acetylcholine release in hippocampal slices occurs at a
      receptor occupancy of only 0.13% and 95% of maximal inhibition at a receptor
      occupancy of 7.5%, suggesting the presence of a receptor reserve that is large
      compared with other G protein-coupled receptor systems in the central nervous
      system. In behavioral experiments, WIN 55212 to 2 inhibited spontaneous locomotor
      activity in mice with an ED50 of 0.3 mg/kg, i. v. In in vivo binding experiments
      using [131I]AM 281, WIN 55212 to 2 failed to produce significant inhibition of
      radiotracer binding in the mouse brains, except at very high doses (10 mg/kg or
      greater, i. v.). By contrast, the CB1 antagonist SR 141716A (10 mg/kg, i.p.),
      completely abolished specific [131I]AM 281 binding. These experiments suggest
      that behavioral effects of cannabinoids, like neurochemical effects, are produced
      at very low receptor occupancy.

PMID- 9918550
TI  - Probing the "active site" of diamine oxidase: structure-activity relations for
      histamine potentiation by O-alkylhydroxylamines on colonic epithelium.
AB  - The responses of the canine colonic epithelium to histamine are potentiated by O
      alkylhydroxylamines. A study of a series of such compounds suggested that active
      compounds had the structure R-O-NH2, substitution of a nitrogen led to total loss
      of activity. The locus of the potentiation effect was traced to the inhibition of
      diamine oxidase. A new series of aliphatic and aromatic O-alkylhydroxylamines
      were synthesized to explore further the structure-activity relations of this
      effect. The potentiating effects of these compounds were determined by examining
      the changes in short circuit current (Isc) produced by histamine and from the
      activity of a soluble preparation of diamine oxidase. We found that 1) branched
      compounds are less active than their straight chain counterparts, 2) greater
      steric bulk of the aliphatic substituent decreased activity, 3) the presence of a
      double bond had no significant effect though a triple bond reduced activity, 4)
      longer straight chain compounds were less active than the shorter chain
      derivatives and 5) all benzylic compounds were less active than the straight
      chain aliphatics. O-1-benzyl was inactive however the meta or para oxygen
      substituted compounds as well as the O-(1-E-Cinnamyl) derivative were active. A
      current model for the action of diamine oxidase proposes a crucial role for a
      trihydroxyphenylalanine quinone cofactor as part of the active site together with
      a copper atom. Using molecular modeling based on our inhibition data we are able
      to define the region of space that is just beyond the reactive carbonyl of the
      trihydroxyphenylalanine residue at the active site of diamine oxidase. We suggest
      that a negatively charged species, such as an aspartate or a glutamate, resides
      in a trough about 7 to 8 A from the trihydroxyphenylalanine carbonyl carbon and
      this species aids in the strong selective binding of substrates such as
      putrescine and histamine.

PMID- 9918549
TI  - Tetrazepinones are equally cytotoxic to Mer+ and Mer- human tumor cell lines.
AB  - Human brain and colon tumor cell lines SF-188 (Mer+) and WiDR (Mer+), which
      express the DNA repair protein O6-methylguanine-DNA methyl transferase (MGMT),
      were 3- to 30-fold less sensitive to temozolomide, mitozolomide, and N, N'-bis(2
      chloroethyl)-N-nitrosourea (BCNU) than the MGMT-deficient tumor cells SF-126 (Mer
      ) and BE (Mer-). This differential sensitivity was not observed when these cells
      were exposed to the novel tetrazepinones PYRZ, NIME, QUINCL, and PYRCL, which
      contain, like temozolomide and mitozolomide, a ureido-triazene moiety. Flow
      cytometric studies revealed that temozolomide induced G2-M arrest in the Mer-
      cells, but exerted a minor effect on the cycle of the Mer+ cells. Similarly,
      mitozolomide (25-100 microM) induced a stronger S-phase arrest in the SF-126
      cells than in the SF-188 cells. In the same dose range (25-100) BCNU induced a
      significant cell cycle accumulation in G22-M in the SF-126 cells but little in
      the SF-188 cell line. In contrast, the cell cycle effects of the tetrazepinones
      were independent of the cell phenotypes. When O6-benzylguanine (O6-BG) was used
      to deplete MGMT activity in the SF brain tumor cell lines, significant
      potentiation of temozolomide (67-fold), mitozolomide (7-fold), and BCNU (3-fold)
      was observed in the SF-188 cell line. By contrast, O6-BG did not potentiate PYRZ,
      PYRCL, QUINCL, and NIME. Moreover, an MGMT inhibitory assay showed that all the
      tetrazepinones were capable of inactivating MGMT in the SF-188 cell line, the
      strongest inhibitor being PYRCL. The results suggest that, unlike temozolomide,
      mitozolomide, and BCNU, the cytotoxicity of the tetrazepinones does not correlate
      with the alkylation of the O6 position of guanine and that the mechanism of MGMT
      inactivation by tetrazepinones may differ from that of hitherto known inhibitors.

PMID- 9918551
TI  - Endogenous opioids regulate the expression of inducible nitric oxide synthase by
      splenocytes.
AB  - In the present study, we tested the hypothesis that lipopolysaccharide (LPS)
      induced expression of nitric oxide synthase (iNOS) by splenocytes is modulated
      through the activation of endogenous opioids in the central nervous system. The
      initial studies determined the parameters of LPS-induced expression of iNOS by
      splenocytes. Rats were injected with LPS at doses of 0, 1, 10, 100, and 1000
      microg/kg, and measures of both iNOS mRNA and protein showed a dose-dependent
      increase in expression. In a time course study, rats received 100 microg/kg LPS
      and were killed at 0, 2, 4, 8, and 16 h postinjection. Both iNOS mRNA and protein
      expression was detectable at the 2-h time point, with peak expression occurring
      at 8 h. To evaluate the involvement of endogenous opioids, the opioid receptor
      antagonist naltrexone was administered at 0, 0.1, 1, or 10 mg/kg s.c. in
      combination with LPS (100 microg/kg), with a second injection of naltrexone at
      the same dose 4 h after the injection of LPS. Naltrexone induced a pronounced
      dose-dependent reduction in iNOS mRNA and protein expression by splenocytes. The
      modulation of iNOS expression occurs via central opioid receptors as
      intracerebroventricular administration but not peripheral administration of N
      methylnaltrexone, the quaternary form of naltrexone that does not readily cross
      the blood-brain barrier, reduced the expression of iNOS. For all of the
      manipulations, nitrite/nitrate levels in the plasma showed effects similar to
      those for iNOS mRNA and protein. Collectively, these findings indicate that
      central opioid receptors are involved in the in vivo regulation of splenic nitric
      oxide production.

PMID- 9918552
TI  - Effects of ethanol treatment on epididymal secretory products and sperm
      maturation in albino rats.
AB  - Alcoholics are often associated with fertility disturbances with low sperm count
      and impaired sperm motility. Spermatozoa attains forward motility and fertilizing
      capacity during their transit through the epididymis. Epididymal secretory
      products form a suitable microenvironment, which favors sperm maturation. To
      study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body
      weight as 25%, v/v) was given by gastric intubation twice daily for 30 days, and
      in another group, rats given treatment for 30 days were withdrawn of treatment
      for a further period of 30 days to assess the reversibility of ethanol-induced
      changes. Serum and epididymidal testosterone and dihydrotestosterone (DHT),
      epididymidal tissue and sperm carnitine, acetyl carnitine, glycerylphosphoryl
      choline (GPC), and sialic acid were studied along with epididymidal sperm count
      and cauda epididymidal sperm motility. Ethanol treatment significantly reduced
      the epididymal tissue/sperm carnitine, acetyl carnitine, GPC, and sialic acid,
      suggesting its adverse effect on these secretory products. Impaired cauda
      epididymidal sperm motility and fertility (in vivo) of ethanol-treated rats imply
      the defective sperm maturation. All these changes were reverted back to normalcy
      after withdrawal of ethanol treatment, indicating the transient effects of
      ethanol. In conclusion, it is evident that ethanol has an adverse effect on sperm
      maturation, which may be affected due to the decrease in serum/epididymal
      testosterone and DHT level and epididymal secretory products.

PMID- 9918553
TI  - Anticoagulant and antithrombotic activity of maltodapoh, a novel sulfated
      tetrasaccharide.
AB  - Orally bioavailable anticoagulants are needed that exhibit rapid and predictable
      onset and offset kinetics. This study was designed to determine whether
      maltodapoh, a novel sulfated bis-maltobionic acid amide, exhibits anticoagulant
      and antithrombotic activity in vivo after oral administration. Maltodapoh
      exhibited a dose-dependent increase in activated partial thromboplastin time
      (aPTT) in both rabbit and human plasma in vitro. Maltodapoh also induced a dose
      dependent increase in aPTT when administered either i.v. or p.o. in rabbits.
      After a single oral bolus (3 mg/kg), aPTT increased 2- to 3-fold between 4 and 8
      h and remained elevated for at least 24 h. This dose doubled the time to the
      onset of thrombotic occlusion after electrical injury to the carotid artery (from
      52 +/- 12 min in vehicle-treated, control rabbits, n = 7, to 98 +/- 12 min in
      maltodapoh-treated animals, n = 7, P <.001) and reduced by 84% the weight of
      thrombus in the superior vena cava induced over 2 h after insertion of a
      thrombogenic copper wire and thread device (from 37 +/- 10 mg in controls to 6 +/
      3 mg in maltodapoh-treated animals, P <.001). Thus, based on the in vivo
      activity after oral administration, favorable kinetic profile and efficacy for
      inhibition of both arterial and venous thrombosis, further testing of this class
      of compounds appears warranted.

PMID- 9918554
TI  - Inhibitory effects of proadrenomedullin N-terminal 20 peptide on antidiuresis and
      norepinephrine overflow induced by stimulation of renal nerves in anesthetized
      dogs.
AB  - The effects of proadrenomedullin N-terminal 20 peptide (PAMP) on changes in renal
      function and norepinephrine (NE) overflow induced by renal nerve stimulation
      (RNS) were examined in anesthetized dogs. The intrarenal arterial infusion of
      PAMP (10, 50, 100 ng/kg/min) did not influence basal levels of systemic and renal
      hemodynamics, or urine formation. RNS at a low frequency (0.5-2.0 Hz) caused
      significant decreases in urine flow and urinary excretion of sodium, and
      increases in NE secretion rate (NESR), without affecting renal hemodynamics. RNS
      at a high frequency (2.5-5.0 Hz), which diminishes renal hemodynamics, elicited
      more potent decreases in urine formation and increases in NESR. The low frequency
      RNS-induced reductions in urine formation and increases in NESR were almost
      completely abolished by the intrarenal arterial infusion of PAMP at 50 ng/kg/min,
      a dose that produced no alterations on basal renal hemodynamics and excretory
      responses. In contrast, high frequency RNS-induced renal vasoconstriction and
      reductions in urine formation, and increases in NESR were not affected by
      infusion of the peptide. We next examined the effect of PAMP on exogenously
      applied NE-induced renal actions, to determine if PAMP functions suppressively at
      postjunctional sites. The intrarenal arterial infusion of NE (100-150 ng/kg/min)
      produced a significant renal vasoconstriction and a reduction in urine formation,
      responses not affected by the administration of PAMP (50 ng/kg/min). From these
      findings, we suggest that PAMP functions as an inhibitory modulator of renal
      noradrenergic neurotransmission, via prejunctional mechanisms, and plays an
      important role in regulating renal functions.

PMID- 9918555
TI  - Novel terpenoid-type quinones isolated from Pycnanthus angolensis of potential
      utility in the treatment of type 2 diabetes.
AB  - Using an ethnomedical-based drug discovery program, two previously unknown
      compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that
      lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP
      18905 are terpenoid-type quinones that significantly lowered plasma glucose
      concentration (p <.05) when given orally to either ob/ob or db/db mice, both of
      which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP
      18904 and SP-18905 were associated with significant decreases in plasma insulin
      concentrations (p <.05), suggesting that both compounds lowered glucose by
      enhancing insulin-mediated glucose uptake. This was supported by the insulin
      suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice
      and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion.
      As such, these two terpenoid-type quinones represent a new class of compounds of
      potential use in the treatment of type 2 diabetes.

PMID- 9918556
TI  - Pharmacokinetic-pharmacodynamic modeling of the psychomotor stimulant effect of
      cocaine after intravenous administration: timing performance deficits.
AB  - We investigated dose-response cocaine pharmacokinetic and metabolite profiles in
      a within-subject design after intravenous bolus cocaine administration (1-4
      mg/kg) in rats under a food-limited regimen. Cocaine was rapidly distributed
      (T1/2beta = 1.09 min) and eliminated (T1/2alpha = 14.93 min). Norcocaine was not
      detected. The free fraction of cocaine was 31.3-33.1% for serum cocaine
      concentrations of 0.5 to 1 microg/ml. Parallel pharmacodynamics was studied using
      performance on a contingency-controlled timing behavior, a differential
      reinforcement of low rate schedule (45 s) in 3-h sessions. Cocaine increased the
      shorter-response rate and decreased the density of reinforcement in a dose- and
      time-related fashion. The increased shorter-response rate is the stimulatory
      effect herein reported. The changes in shorter-response rate and the density of
      reinforcement were directly interpretable as functions of cocaine concentrations
      in the respective hypothetical effect compartments by using sigmoidal Emax and
      inhibitory Emax models, respectively. Because the concentration at half of Emax
      for the shorter-response rate (EC50 = 0.467 microg/ml) was greater than that for
      density of reinforcement (IC50 = 0.070 microg/ml), the former began to return
      toward baseline sooner than the latter. Only as cocaine concentration decreased
      to values smaller than the EC50 did the density of reinforcement begin to return
      toward baseline. Thus, the density of reinforcement is an index for evaluating
      the deficit in timing performance. The concentration-effect plot confirmed that
      the intensity of the effects of cocaine depends solely on concentration
      regardless of the dose. These results demonstrated that the pharmacokinetic
      pharmacodynamic analysis allows the identification of the stimulant action of
      cocaine, which in turn delineates its consequence on timing performance.

PMID- 9918557
TI  - Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate
      receptor channels in rat hippocampal neurons.
AB  - We investigated in rat hippocampus neurons whether 4-(aminobutyl)guanidine
      (agmatine), formed by decarboxylation of L-arginine by arginine decarboxylase and
      metabolized to urea and putrescine, can modulate the function of N-methyl-D
      aspartate (NMDA) receptor channels. In cultured hippocampal neurons studied by
      whole-cell patch clamp, extracellular-applied agmatine produced a voltage- and
      concentration-dependent block of NMDA but not alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid nor kainate currents. Analysis of the voltage dependence
      of the block suggests that agmatine binds at a site located within the NMDA
      channel pore with a dissociation constant of 952 microM at 0 mV and an electric
      distance of 0.62. We also tested effects of several agmatine analogs. Arcaine
      (1,4-butyldiguanidine) also produced a similar voltage-dependent block of the
      NMDA current, whereas putrescine (1, 4-butyldiamine) had little effect,
      suggesting that the guanidine group of agmatine is the active moiety when
      blocking the NMDA channel. Moreover, spermine (an endogenous polyamine)
      potentiated the NMDA current even in the presence of blocker agmatine or arcaine,
      suggesting that the guanidine-containing compounds agmatine and arcaine interact
      with the NMDA channel at a binding site different from that of spermine. Our
      results indicate that in hippocampal neurons agmatine selectively modulates the
      NMDA subclass of glutamate receptor channels mediated by the interaction between
      the guanidine group and the channel pore. The results support other data that
      agmatine may function as an endogenous neurotransmitter/neuromodulator in brain.

PMID- 9918558
TI  - Effects of phentermine on responding maintained under multiple fixed-ratio
      schedules of food and cocaine presentation in the rhesus monkey.
AB  - Drugs that decrease drug-maintained responding at doses that do not decrease
      other behaviors in animals may be suitable candidates for development as
      medications to treat drug abuse in humans. The present study examined whether
      this effect could be obtained with phentermine, a drug that has been reported to
      decrease cocaine intake in humans. Rhesus monkeys were trained under multiple
      fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine
      was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3
      10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease,
      or decreased less, food-maintained responding for each of three unit doses of
      cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or
      5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food
      maintained responding. After subacute treatment was terminated, rates of cocaine
      maintained responding generally recovered to levels comparable to those seen
      during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally
      increase responding associated with a very low (1 microg/kg/injection) unit dose
      of cocaine, suggesting that the decrease in cocaine-maintained responding at
      higher unit doses was not the result of a leftward shift in the cocaine unit dose
      effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1
      [2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909)
      (30 microg/kg/injection) at doses similar to those that decreased food-maintained
      responding. These results show that phentermine is effective in decreasing
      cocaine self-administration and suggest that it may be an effective medication
      for cocaine abuse.

PMID- 9918560
TI  - Hepatobiliary transport governs overall elimination of peptidic endothelin
      antagonists in rats.
AB  - The overall disposition and hepatobiliary transport of BQ-123, an anionic
      cyclopentapeptide, and three analogs were examined in rats in vivo. Total body
      clearance (CLtotal) and biliary excretion clearance (CLbile, p) exhibited 4- to 8
      fold differences between the compounds, with those for BQ-485 and compound A
      having the highest and lowest values, respectively. The CLbile, p values of BQ
      485, BQ-123, and BQ-518 were almost equal to the CLtotal, suggesting that
      hepatobiliary transport is the major elimination pathway for these compounds.
      Hepatic uptake clearance (CLuptake, vivo) and biliary excretion clearance
      (CLbile, h/fT), which was defined for the hepatic unbound concentration, were
      separately determined to examine the hepatic uptake and excretion processes,
      respectively. Both the CLuptake, vivo and CLbile, h/fT of BQ-485 were higher than
      those of BQ-123, whereas the corresponding values for BQ-518 were similar to
      those for BQ-123. The CLuptake, vivo and CLbile, h/fT of compound A were,
      respectively, approximately two thirds and one half those of BQ-123, suggesting
      that the lower CLbile, p value is due to the low efficiency of both the uptake
      and excretion processes. The CLuptake, vivo of these four peptides in vivo was
      similar to the extrapolated values based on the carrier-mediated transport
      activity previously assessed in vitro in isolated rat hepatocytes. The primary
      active transport previously assessed in an in vitro study in canalicular membrane
      vesicles was also highest for BQ-485 and lowest for compound A, similar to
      CLbile, h/fT in vivo. Thus, the transporters on both the sinusoidal and
      canalicular membranes determine the efficiency of the peptide overall elimination
      from the circulation.

PMID- 9918559
TI  - Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after
      discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2
      (Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins.
AB  - Long-term exposure to fluoxetine produces a desensitization of hypothalamic
      postsynaptic 5-hydroxytryptamine (5-HT)1A receptors, indicated by a substantial
      inhibition of the 5-HT1A receptor-mediated stimulation of oxytocin and
      adrenocorticotropic hormone (ACTH) secretion. The present study investigated the
      time course and mechanism of this desensitization after discontinuation of
      fluoxetine administration. Male rats were injected with saline or fluoxetine (10
      mg/kg/day, i.p.) for 14 days and were challenged with a 5-HT1A agonist, [8
      hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) 50 microg/kg, s.c.] 2, 4, 7, 14,
      28, or 60 days post-treatment. In control animals, 8-OH-DPAT significantly
      increased (approximately 15-fold) plasma levels of oxytocin and ACTH. At 2 days
      post-treatment, oxytocin and ACTH responses to 8-OH-DPAT were reduced by 74% and
      68%, respectively. During further withdrawal from fluoxetine, there was a gradual
      increase in the oxytocin response toward control levels. However, even 60 days
      after discontinuation of fluoxetine, the oxytocin response was still
      significantly reduced by 26% compared with controls. In contrast, the suppressed
      ACTH response to 8-OH-DPAT (a less-sensitive indicator of desensitization)
      gradually returned to control levels by day 14 of withdrawal from fluoxetine.
      Interestingly, the sustained reductions in the hormone responses occurred in the
      absence of reductions in Gz or Gi protein levels in the hypothalamus.
      Furthermore, this desensitization was sustained in the absence of detectable
      levels of fluoxetine and norfluoxetine in plasma and brain tissue. These findings
      suggest that the sustained desensitization of hypothalamic 5-HT1A receptor
      systems, observed during fluoxetine withdrawal, may be due to altered
      interactions among the protein components of the 5-HT1A receptor system, rather
      than their absolute levels.

PMID- 9918562
TI  - SR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as
      an inverse agonist.
AB  - In the present report, we investigated in detail the effects of SR 144528, a
      selective antagonist of the peripheral cannabinoid receptor (CB2), on two well
      characterized functions mediated by CB2: the induction of the early response gene
      krox24 and the inhibition of adenylyl cyclase. We generated Chinese hamster ovary
      cells doubly transfected with human CB2 and a luciferase reporter gene linked to
      either the murine krox24 regulatory sequence or multiple cAMP responsive
      elements. Our results show that (1) SR 144528 antagonizes the effect of receptor
      agonists-it inhibits the krox24 reporter activity and prevents the inhibition of
      forskolin-induced cAMP reporter activity mediated by CP 55,940; (2) CB2 is
      autoactivated-CB2 mediates signaling in the absence of ligand, and this basal
      activity is reduced by pretreating the cells with pertussis toxin; (3) SR 144528
      is an inverse agonist-it reproduces the effects of pertussis toxin; and (4)
      inhibition of precoupled CB2 by a long-term pretreatment of cells with SR 144528
      potentiates krox24 response to cannabinoid receptor agonists and restores
      activation of adenylyl cyclase. Taken together, these data provide evidences for
      the inverse agonist property of SR 144528 and the constitutive activation of CB2
      in Chinese hamster ovary-expressing cells.

PMID- 9918561
TI  - Primary active transport of peptidic endothelin antagonists by rat hepatic
      canalicular membrane.
AB  - The biliary excretion mechanism of three derivatives of BQ-123, an anionic
      cyclopentapeptide, was examined using isolated canalicular membrane vesicles
      (CMVs) from Sprague-Dawley rats. The uptake by CMV of BQ-485, a linear peptide,
      BQ-518, a cyclic peptide, and compound A, a cyclic peptide with a cationic
      moiety, was stimulated by ATP. An "overshoot" phenomenon and saturation were
      observed for the ATP-dependent uptake of these three peptides. The Michaelis
      Menten constants (Km) for the uptake of BQ-485 and BQ-518 were comparable to the
      inhibition constants (Ki) for their inhibitory effects on ATP-dependent [3H]BQ
      123 uptake. The uptake of BQ-485 showed the highest value and was inhibited by BQ
      123 with a Ki that was comparable to the Km for BQ-123 uptake. The ATP-dependent
      uptake of BQ-123, BQ-485, and BQ-518 was much lower in CMVs from Eisai
      hyperbilirubinemic rats, a strain having a hereditary defect of the canalicular
      multispecific organic anion transporter (cMOAT). These results suggest that both
      BQ-485 and BQ-518 principally share the cMOAT transporter with BQ-123. Compound A
      almost completely inhibited BQ-123 uptake, although its ATP-dependent uptake was
      much lower than that of the other three peptides. The ATP-dependent uptake of
      compound A was not very different in Sprague-Dawley rats and Eisai
      hyperbilirubinemic rats and was not inhibited by S-(2, 4-dinitrophenyl)
      glutathione, a typical substrate for cMOAT. Thus, although compound A inhibits
      cMOAT-mediated transport, its own transport by cMOAT is minimal and mediated by
      another transporter. This low degree of primary active transport by cMOAT may be
      the principal reason for its relatively longer residence in the circulation.

PMID- 9918563
TI  - Atypical neuroleptics enhance histamine turnover in brain via 5
      Hydroxytryptamine2A receptor blockade.
AB  - Clozapine and olanzapine behave as weak H3-receptor antagonists in vitro with Ki
      values around 1 and 50 microM, respectively. Despite these modest apparent
      affinities, both compounds given orally to mice, nearly doubled steady-state tele
      methylhistamine levels in brain, with ED50 values as low as 1 and 3 mg/kg,
      respectively, an effect comparable to those of potent H3-receptor antagonists.
      This effect corresponded to an enhancement of histamine turnover rate from 45 to
      73 ng/g/h as measured in the case of olanzapine using the pargyline test. Other
      antipsychotics displaying, such as clozapine and olanzapine, high 5
      hydroxytryptamine (5-HT)2A receptor antagonist potency, i.e., risperidone,
      thioridazine, seroquel, and iloperidone, also enhanced markedly tele
      methylhistamine levels. This effect was 1) additive with that of a pure H3
      receptor antagonist, ciproxifan, 2) mimicked by a 5-HT2A receptor antagonist,
      ketanserin, 3) reversed by a 5-HT2A receptor agonist, DOI, 4) not shared by
      antipsychotics with low affinity for the 5-HT2A receptor, i.e., haloperidol,
      sulpiride, raclopride, or remoxipride that, on the contrary, tended to reduce
      tele-methylhistamine levels. We conclude that in contrast to "typical"
      antipsychotics, "atypical" antipsychotics stimulate histamine neuron activity via
      blockade of the 5-HT2A receptor in vivo. This effect does not appear to account
      for their reduced extrapyramidal side-effects but may underlie their pro
      cognitive properties.

PMID- 9918564
TI  - Differences in excretion of hippurate, as a metabolite of benzoate and as an
      administered species, in the single-pass isolated perfused rat kidney explained.
AB  - The extents of excretion of [14C]hippurate and [3H]hippurate were compared in the
      single-pass, constant flow (8 ml/min) isolated rat kidney which was perfused
      simultaneously with tracer concentrations of [14C]benzoate and [3H]hippurate. The
      steady-state renal extraction ratio of [14C]benzoate was 0.26 +/- 0.04 and was
      associated with a renal clearance of 1.13 +/- 0.17 ml/min/g. The urinary
      clearance of [14C]benzoic acid was low (0.011 +/- 0.01 ml/min/g), yielding a low
      fractional excretion [unbound urinary clearance/glomerular filtration rate (GFR)]
      value of 0.27 +/- 0.19 and suggesting that glycination of [14C]benzoate to
      [14C]hippurate accounted almost completely for the total renal clearance.
      Fractional excretion for preformed [3H]hippurate was eight times that of GFR, but
      the steady-state renal extraction ratio of preformed [3H]hippurate, E(pmi) (0.24
      +/- 0.05) was much lower than the apparent extraction ratio of the renally formed
      [14C]hippuric acid [E(mi) = 0.39 +/- 0.09] (p <.05). The theoretical basis for
      the discrepancy was explored with mathematical formulations developed from a
      physiologically based model of the kidney. It was found that parent drug kinetic
      parameters (transport and metabolic intrinsic clearance of benzoate) were
      unimportant for E(mi) or E(pmi). Rather, the value of EK(mi) exceeded EK(pmi)
      because of the ratio of efflux clearances at the basolateral and luminal
      membranes for hippurate [corrected] was less than 26.089, a value determined by
      the GFR, plasma renal flow, and the unbound fraction of hippurate of the system
      that would render E(mi) to equal E(pmi) in the system. The influx clearance for
      hippurate to enter from plasma to cell at the basolateral membrane and the
      reabsorption clearance of hippurate to enter from tubular urine to cell at the
      luminal membrane failed to alter the ratio of EK(pmi)/EK(mi).

PMID- 9918565
TI  - Contribution of cytochrome P-4502D6 phenotype to the neuromodulatory effects of
      dextromethorphan.
AB  - Dextromethorphan (DEM)-mediated N-methyl-D-aspartate receptor blockade may result
      from an action of unchanged DEM or its active metabolite, dextrorphan (DOR). In
      humans, DEM is metabolized into DOR by the polymorphic enzyme CYP2D6. We
      therefore investigated the impact of quinidine (Qd), a selective inhibitor of
      CYP2D6, on DEM disposition and the contribution of CYP2D6 phenotype on DEM
      antinociceptive and neuromodulatory effects. Using a randomized, double-blind,
      crossover, placebo-controlled design, healthy volunteers (n = 7) received Qd (50
      mg Qd sulfate orally) or a placebo and, 12 h later, either DEM (50 mg DEM
      hydrobromide orally) or a placebo. DEM and DOR pharmacodynamics were assessed for
      their antinociceptive and neuromodulatory effects. Antinociceptive effects were
      assessed over 4 h by subjective pain threshold and RIII nociceptive reflex (RIII)
      monitoring. Neuromodulatory effects were studied using the primary and secondary
      hyperalgesia induced by the topical application of capsaicin. Two of seven
      subjects were genotypic CYP2D6 PM. Pretreatment of EM by Qd suppressed DOR
      formation and increased the plasma level of DEM to the levels of poor
      metabolizers. In poor metabolizers, DEM induced a significant increase in
      objective (+45%) and subjective (+35%) pain thresholds. In extensive
      metabolizers, only a slight and short-lasting increase in the subjective
      threshold was observed, whereas no effect was seen on the objective threshold.
      DEM modulates secondary hyperalgesia compared with DOR. The CYP2D6 phenotype
      affects the disposition of DEM and the production of the active metabolite DOR.
      The impact of the CYP2D6 phenotype is of major importance for the spinal
      antinociceptive and neuromodulatory effects of DEM.

PMID- 9918566
TI  - Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells
      and inhibits topoisomerase I.
AB  - Antiproliferative action of different pentacyclic triterpenes has repeatedly been
      reported, and some lipoxygenase inhibitors have been shown to induce cell death
      in various cell systems. Acetyl-11-keto-beta-boswellic acid (AKBA) is a
      pentacyclic triterpene that inhibits 5-lipoxygenase in a selective,
      enzymedirected, nonredox, and noncompetitive manner. To investigate a possible
      effect of AKBA on leukemic cell growth, proliferation of HL-60 and CCRF-CEM cells
      was assayed in the presence of AKBA and a structural analog without effect on 5
      lipoxygenase, amyrin. Cell counts and [3H]thymidine incorporation were
      significantly reduced in a dose-dependent manner in the presence of AKBA (IC50 =
      30 microM) but not amyrin. An additive effect of AKBA with the crosslinking of
      the CD95 receptor was also observed. Flow cytometric analysis of propidium iodide
      stained cells indicated that the cells underwent apoptosis. This was confirmed by
      flow cytometric detection of sub-G1 peaks in AKBA-treated cells and by DNA
      laddering. However, because HL-60 and CCRF-CEM do not express 5-lipoxygenase mRNA
      constitutively, a mechanism distinct from inhibition of 5-lipoxygenase must
      account for the effect of AKBA. In a DNA relaxation assay with phiX174RF DNA,
      AKBA inhibited topoisomerase I from calf thymus at concentrations of >/=10
      microM. A semiquantitative cDNA polymerase chain reaction approach was used to
      estimate the relative level of expression of topoisomerases in both cell lines.
      The data suggest that induction of apoptosis in HL-60 and CCRF-CEM by AKBA may be
      due to inhibition of topoisomerase I in these cells.

PMID- 9918567
TI  - Epidermal growth factor protects rat epithelial cells against acid-induced damage
      through the activation of Na+/H+ exchangers.
AB  - We examined the effect of epidermal growth factor (EGF) on acid-induced cell
      damage in rat gastric epithelial cells (RGM1) and investigated the mechanisms of
      this effect. Cells were incubated with EGF for 5, 15, 30, and 60 min, and then
      immersed in an acidified medium (pH 4.0) for 30 min to induce cell damage. EGF
      prevented cell damage in a concentration- and time-dependent manner. EGF reduced
      the effects of the acidified medium on the cells, preventing the reduction of
      intracellular pH. Replacement of Na+ with K+ in the acidified medium canceled the
      effect of EGF. Indomethacin and W-7 (a Ca-calmodulin inhibitor) did not alter the
      protective effect of EGF. In contrast, genistein (a tyrosine kinase inhibitor),
      amiloride (a Na+/H+ exchangers I and II inhibitor), and wortmannin (a
      phosphatidylinositol 3-kinase inhibitor) significantly decreased the effect of
      EGF. Expression of Na+/H+ exchangers type I and type II was confirmed by reverse
      transcription-polymerase chain reaction. Our results demonstrate that EGF
      prevents acid-induced cell damage, most likely through the activation of a Na+/H+
      exchanger II via phosphatidylinositol 3-kinase.

PMID- 9918568
TI  - Contribution of organic anion transporting polypeptide to uptake of its possible
      substrates into rat hepatocytes.
AB  - Organic anion transporting polypeptide (oatp1) has been cloned from rat liver as
      one of the transporters responsible for the hepatic uptake of ligands, and its
      substrate specificity has been determined. However, the contribution of oatp1 to
      the Na+-independent uptake of ligands into rat hepatocytes remains to be
      investigated. In the present study, we determined the contribution of oatp1 and
      examined the uptake of ligands into primary cultured hepatocytes (cultured for 4
      h) and into COS-7 cells transiently expressing oatp1 and normalized using
      estradiol-17beta-D-glucuronide as a reference compound. Western blot analysis
      indicated that oatp1 was less extensively glycosylated in transfected COS-7
      cells, and the expression level in transfectant was one-seventh that in rat
      liver. The Km values for the uptake of estradiol-17beta-D-glucuronide were
      similar for cultured hepatocytes and oatp1-transfected COS-7 cells (Km = 12.3
      versus 20.4 microM), although the Vmax value for oatp1-transfected COS-7 cells
      was one-seventh that for cultured hepatocytes (Vmax = 1.30 versus 0.175
      nmol/min/mg protein). The contribution of oatp1 to the Na+-independent uptake of
      taurocholic acid and cholic acid into rat hepatocytes was more than 50 to 60%,
      whereas the corresponding values for the sulfate-conjugates of estrone and 6
      hydroxy-5, 7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole were 20 to
      30%. In addition, the analysis indicated that the contribution of oatp1 to the
      Na+-independent uptake of several ligands [glucuronide-conjugate of 6-hydroxy-5,
      7-dimethyl2-methylamino-4-(3-pyridylmethyl)benzothiazole, ibuprofen, pravastatin,
      ouabain, and 2,4-dinitrophenyl-S-glutathione] was minimal. Collectively, the
      transfected COS-7 cells may be used to quantitatively predict oatp1 activity in
      hepatocytes after correction of its expressed amount. It is also suggested that
      multiple transport mechanisms are responsible for the Na+-independent uptake of
      organic anions into hepatocytes.

PMID- 9918569
TI  - The effects of morphine, nicotine and epibatidine on lymphocyte activity and
      hypothalamic-pituitary-adrenal axis responses.
AB  - Acute administration of morphine alters various neuroendocrine and immune
      parameters via opioid receptors located within the central nervous system.
      Similar effects have been reported after systemic nicotine treatment. To examine
      the possible relationship between opioid and nicotinic receptor activation on the
      immune system, we compared the effects of morphine with both nicotine and the
      highly selective nicotinic agonist, epibatidine. Male Sprague-Dawley rats were
      treated with either morphine (10 mg/kg, s.c.), nicotine (2.85 mg/kg, s.c. = 1
      mg/kg freebase), or epibatidine (5 microg/kg, s.c.) and sacrificed 2 hours later.
      Each drug increased plasma corticosterone levels and decreased the magnitude of
      the peripheral blood lymphocyte proliferation response to the T cell mitogen
      concanavalin A. None of the treatments had a significant effect on splenic or
      thymic lymphocyte responses. The effects of nicotine treatment were dose
      dependent. Pretreatment with the quaternary ganglionic antagonist chlorisondamine
      (0.5 mg/kg, i.p.), completely blocked the effect of epibatidine on blood
      lymphocytes without altering the elevation of corticosterone levels. Although
      naltrexone (10 mg/kg, s.c.) blocked all effects of morphine, the effects of
      epibatidine were not blocked by the opioid receptor antagonist. Furthermore, in
      contrast to morphine (), central injection of neither nicotine (30 or 240 nmol)
      nor epibatidine (5, 50, or 500 ng) altered blood lymphocyte responses. These
      results suggest that, like morphine, nicotinic agonists decrease blood lymphocyte
      proliferation responses, apparently independent of elevated corticosterone.
      However, unlike morphine, nicotinic agonists appear to act predominantly at
      peripheral receptors, suggesting that nicotinic receptors are downstream of
      opioid receptors in a centrally mediated opioid-induced immunomodulatory pathway.

PMID- 9918570
TI  - Disruption of prepulse inhibition and increases in locomotor activity by
      competitive N-methyl-D-aspartate receptor antagonists in rats.
AB  - Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as
      phencyclidine are psychotomimetics and disrupt prepulse inhibition (PPI), a
      measure of sensorimotor gating that is deficient in schizophrenia. Systemically
      administered competitive NMDA receptor antagonists do not disrupt PPI in rats,
      leading to speculation that these compounds might have use as neuroprotective
      agents without the risk of psychotomimetic side effects. The effects on
      sensorimotor gating and locomotor activity of competitive NMDA receptor
      antagonists that either penetrate (SDZ 220-581 and SDZ EAB-515) or poorly
      penetrate [SDZ EAA-494 (D-CPPene)] the blood-brain barrier were compared. Rats
      were treated with either SDZ 220-581 (0, 2.5, or 5.0 mg/kg) or SDZ EAB-515 (0,
      3.0, 10.0, or 30.0 mg/kg) and tested for PPI and locomotor activity. Different
      rats were tested for PPI after either systemic (0, 0.5, 1.0, or 5.0 mg/kg) or
      intra-amygdala (0 or 1.0 microg/microl) administration of D-CPPene. Finally, rats
      were pretreated with clozapine (0 or 5.0 mg/kg) or haloperidol (0 or 0.1 mg/kg),
      together with SDZ 220-581 (0 or 2.5 mg/kg), and tested. SDZ 220-581 and SDZ EAB
      515 decreased PPI without affecting startle magnitude. Reduced PPI was noted
      after central but not systemic administration of D-CPPene. The gating deficits
      produced by SDZ 220-581 were blocked by clozapine or haloperidol. Movement
      pattern analysis indicated that locomotor activity was increased by SDZ 220-581
      and SDZ EAB-515 in a phencyclidine-like manner. These results indicate that
      competitive NMDA receptor antagonists, if they gain sufficient access to the
      brain, produce a behavioral profile that resembles that of the psychotomimetic
      noncompetitive antagonists.

PMID- 9918571
TI  - Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal
      cerebral ischemic/reperfusion injury.
AB  - The neuroprotective properties of drugs binding to FKBP12, with and without
      subsequent inhibition of calcineurin, were investigated in rat models of ischemic
      embolic stroke. Drug effects on brain infarct volumes evoked by transient middle
      cerebral artery occlusion (MCAO) and by permanent MCAO were determined in vivo by
      T2-weighted magnetic resonance imaging and post mortem by triphenyltetrazolium
      chloride staining and histology. Drugs binding to FKBP12 and inhibiting
      calcineurin, such as FK506 and SDZ ASM 981, dose dependently reduced the infarct
      volumes, determined 48 h after MCAO by both magnetic resonance imaging and
      triphenyltetrazolium chloride staining but only in the transient MCAO model. In
      vivo potencies to reduce brain infarcts paralleled the in vitro potencies to
      inhibit calcineurin. Histological staining after 6 days of survival showed that
      the neuroprotective effects were permanent. Rapamycin, known to bind with similar
      affinity to FKBP12 but not to inhibit calcineurin, was not neuroprotective but
      abolished the neuroprotective effects of FK506 when coadministered. In the
      permanent MCAO models, FK506 showed no effect when injected before and little
      effect when injected after MCAO. Measurements of core temperatures after MCAO in
      controls and drug-treated rats do not support hypothermia being the mechanism
      responsible for neuroprotection. We conclude that drugs inhibiting calcineurin
      activity are neuroprotective in focal cerebral ischemia/reperfusion but not in
      permanent ischemia models, possibly by preventing reperfusion injury.

PMID- 9918572
TI  - Ropivacaine inhibits serum-induced proliferation of colon adenocarcinoma cells in
      vitro.
AB  - Ropivacaine, a new long-acting local anesthetic, is currently being investigated
      for the treatment of ulcerative colitis. In view of the increased incidence of
      dysplasia and neoplasia associated with ulcerative colitis, it is important that
      the medical treatment of these patients does not stimulate cell proliferation
      further. This study was performed to evaluate the effect of ropivacaine on the
      proliferation of human colon adenocarcinoma cells (HT-29 and Caco-2) in vitro. A
      serum-induced proliferation assay of human colon adenocarcinoma cells was used.
      Ropivacaine inhibited the growth of HT-29 and Caco-2 cells in a dose-dependent
      manner. Fifty percent inhibition of growth was found at a ropivacaine
      concentration of 250 microM when the HT-29 cells were cultured in 1% fetal calf
      serum and of 550 microM when the HT-29 cells were cultured in 10% serum. The
      effective concentrations are within the range of the therapeutic concentrations
      obtained in the colon of patients treated rectally with ropivacaine. Lidocaine,
      hydrocortisone, and 5-aminosalicylic acid were found to be less potent than
      ropivacaine in inhibiting proliferation. Ropivacaine caused a dose-dependent
      membrane depolarization that appeared to correlate with the inhibited cell
      proliferation, whereas the effect was not related to inhibition of leukotriene B4
      or prostaglandin E2. In conclusion, the antiproliferative activity of
      ropivacaine, combined with previously reported anti-inflammatory activities,
      makes this drug an interesting new alternative for the local treatment of
      ulcerative colitis.

PMID- 9918573
TI  - Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating
      red cell substitute.
AB  - A major obstacle in the development of red cell substitutes has been overcoming
      their short circulation persistence. In this study, distearoyl
      phosphoethanolamine polyethylene glycol 5000 (PEG-PE) (10 mol%) was added to the
      formulation of liposome-encapsulated hemoglobin (LEH) to decrease
      reticuloendothelial system uptake and prolong LEH circulation persistence. PEG
      LEH was radiolabeled with technetium-99m, infused into rabbits (25% of blood pool
      at 1 ml/min) (n = 5), and monitored by scintigraphic imaging at various times out
      to 48 h. At 48 h, animals were sacrificed, and tissue samples were collected for
      counting in a scintillation well counter. Tissue distribution data at 48 h
      revealed that 51.3 +/- 3.4% of the technetium-99m-PEG-LEH remained in
      circulation, a greater than 3-fold increase in the circulation half-life compared
      with circulation half-lives previously reported for non-PEG-containing LEH
      formulations. The liver had the greatest accumulation at 48 h (12.7 +/- 0.7%),
      followed by bone marrow (6.2 +/- 0.1%), whereas the spleen had only 1.4 +/- 0.2%.
      The addition of PEG-PE to the LEH formulation greatly prolongs the circulation
      persistence of LEH and represents a significant step in the development of red
      cell substitutes with prolonged oxygen delivery.

PMID- 9918574
TI  - Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and
      thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1.
AB  - We developed mice deficient in protease-activated receptor-2 (PAR-2) or PAR-1 to
      explore the pathophysiological functions of these receptors. In this report, we
      evaluated mean arterial pressure and heart rate (HR) changes in response to PAR-1
      or PAR-2 activation in anesthetized wild-type (WT), PAR-1-deficient (PAR-1(-/-)),
      and PAR-2-deficient (PAR-2(-/-)) mice. In WT mice, TFLLRNPNDK, a PAR-1 selective
      activating peptide, caused hypotension and HR decreases at 1 micromol/kg.
      TFLLRNPNDK also caused secondary hypertension following L-NAME pretreatment.
      These responses were absent in PAR-1(-/-) mice. In WT mice, SLIGRL, a PAR-2
      selective activating peptide, caused hypotension without changing HR at 0.3
      micromol/kg. SLIGRL did not induce hypertension following Nomega-nitrol-arginine
      methyl ester-HCl (L-NAME). The response to SLIGRL was absent in PAR-2(-/-) mice.
      SFLLRN, a nonselective receptor activating peptide caused hypotension and HR
      decreases in WT mice at 0.3 micromol/kg, as well as secondary hypertension
      following L-NAME. SFLLRN still induced hypotension in PAR-1(-/-) mice, but HR
      decrease and secondary hypertension following L-NAME were absent. The hypotensive
      and bradycardic responses to SFLLRN and TFLLRNPNDK in PAR-2(-/-) mice were
      accentuated compared with WT mice. By using mouse strains deficient in either PAR
      1 or PAR-2, we confirmed the in vivo specificity of TFLLRNPNDK and SLIGRL as
      respective activating peptides for PAR-1 and PAR-2, and the distinct hemodynamic
      responses mediated by activation of PAR-1 or PAR-2. Moreover, the accentuated
      response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory
      response and potential receptor cross-talk.

PMID- 9918575
TI  - Finasteride, a 5alpha-reductase inhibitor, blocks the anticonvulsant activity of
      progesterone in mice.
AB  - Progesterone is an effective anticonvulsant against pentylenetetrazol (PTZ)
      seizures. This action is hypothesized to require the metabolic conversion of
      progesterone to the gamma-aminobutyric acidA receptor potentiating neuroactive
      steroid allopregnanolone by 5alpha-reductase isoenzymes followed by 3alpha
      hydroxy oxidoreduction. We evaluated this possibility using the competitive
      5alpha-reductase inhibitor finasteride. Progesterone (50-200 mg/kg, i.p.)
      protected mice against PTZ-induced seizures in a dose-dependent manner (ED50, 94
      mg/kg). Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose
      dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2
      x ED50 dose = 188 mg/kg). In contrast, finasteride (up to 300 mg/kg) failed to
      affect the anticonvulsant activity of allopregnanolone (10-30 mg/kg, i.p.; ED50,
      12 mg/kg). Finasteride (up to 300 mg/kg) did not block the protective effect of
      high doses of progesterone (250-350 mg/kg) on tonic hindlimb extension in the
      maximal electroshock seizure test (progesterone ED50, 235 mg/kg). The
      anticonvulsant activity of progesterone against PTZ-induced seizures can be
      blocked by 5alpha-reductase inhibition, providing strong evidence that the
      anticonvulsant effect of the steroid in this model is mediated by its active
      metabolite allopregnanolone.

PMID- 9918576
TI  - Two genetically selected strains of rats exhibit hypersensitivity or resistance
      to cocaine-induced fatal arrhythmias.
AB  - We identified for the first time two genetically selected strains of rats that
      differ markedly in sensitivity to cocaine-induced life-threatening cardiac
      arrhythmias and arrest. The two strains of rats, designated as Fast and Slow,
      were bred for sensitivity (Fast) or resistance (Slow) to electrically kindled
      seizures. Studies were performed on halothane-anesthetized, mechanically
      ventilated rats. Animals were given cocaine (3 or 4 mg/kg/min i.v.) until they
      died. Arrhythmias (atrioventricular conduction block) developed at much lower
      cumulative cocaine doses in Slow-kindling rats than in Fast-kindling rats (15 +/-
      1 versus 42 +/- 3 mg/kg, p <.01). The lethal cocaine dose (the dose that caused
      cardiac arrest) was also markedly lower in Slow than in Fast strains (32 +/- 2
      versus 62 +/- 6 mg/kg, p <.01). These differences between the two strains were
      not significantly altered by pretreatment of animals with either ganglionic
      blockers, hexamethonium (20 mg/kg i.v.) or chlorisondamine (5 mg/kg i.v.), or a
      nonselective beta adrenergic receptor blocker, propranolol (1 mg/kg i.v.). A
      nonselective alpha adrenergic receptor blocker, phentolamine (10 mg/kg i.v.),
      however, abolished the differences between the Fast and Slow strains in the doses
      of cocaine required to produced atrioventricular conduction block and cardiac
      arrest. The results provide the first evidence of genetically determined
      susceptibility or resistance to cocaine-induced cardiotoxicity. There appears to
      be a genetically determined difference in the alpha adrenergic receptor system
      between the two strains that is responsible for the differential sensitivity to
      cocaine-induced arrhythmias and cardiac arrest.

PMID- 9918577
TI  - Pressor and renal vasoconstrictor responses to acute systemic nitric oxide
      synthesis inhibition are independent of the sympathetic nervous system and
      angiotensin II.
AB  - Acute systemic, nonselective nitric oxide synthesis inhibition (NOSI) causes a
      marked pressor and renal vasoconstrictor response in the normal conscious
      chronically catheterized rat. The present studies directly address the question
      of how these vasoconstrictor responses are related to the combined
      vasoconstrictor activities of the sympathetic nervous system and angiotensin II.
      When the alpha adrenoceptors are blocked (with prazosin) the pressor and renal
      hemodynamic responses to NOSI are unaffected. Combined alpha adrenoceptor and
      angiotensin II receptor blockade at the same time as NOSI results in no net
      change in blood pressure while leaving the renal vasoconstrictor response intact.
      However, when the NOSI is delayed, a substantial and unblunted pressor response
      is seen. In contrast to the vasoconstrictor responses, the natriuretic and
      diuretic responses to acute NOSI are prevented by simultaneous alpha adrenoceptor
      blockade alone and combined with angiotensin II receptor blockade. These findings
      suggest that the hemodynamic actions of acute NOSI in the unstressed rat are
      independent of the sympathetic nervous system and angiotensin II. In contrast,
      the natriuretic/diuretic response to acute NOSI is apparently partly the result
      of some interaction with the sympathetic nervous system, not, as we had
      previously suggested, exclusively the result of a pressure natriuresis.

PMID- 9918578
TI  - Sensitization of amphetamine-induced stereotyped behaviors during the acute
      response.
AB  - The quantitative and qualitative features of the behavioral response to
      amphetamine-like stimulants in rats can be dissociated from the dopamine
      response. This dissociation is particularly evident in the temporal profiles of
      the extracellular dopamine and stereotypy responses to higher doses of
      amphetamine. One possible mechanism contributing to this temporal dissociation is
      that during the acute response to amphetamine, dopamine receptor mechanisms are
      enhanced such that stereotyped behaviors can be supported by synaptic
      concentrations of dopamine which are not sufficient to initiate these behaviors.
      To further explore the dynamics of stimulant sensitivity during the acute
      response, we examined the behavioral and extracellular dopamine responses to a
      low, nonstereotypy-producing dose of amphetamine (0.5 mg/kg) at various times
      after an acute, priming injection of 4.0 mg/kg when stereotypies had subsided and
      extracellular dopamine was approaching predrug baseline levels. The low-dose
      challenge produced intense stereotypies although the regional dopamine responses
      were not significantly different from control animals. Blockade of the expression
      of stereotypies during the priming response by the D2 antagonist haloperidol or
      the D1 antagonist SCH 23390 prevented the expression of an enhanced stereotypy
      response to the challenge injection. Our results suggest that an exposure to
      amphetamine results in a rapid sensitization of the stereotypy response which
      does not involve changes in the extracellular dopamine response but requires
      activation of dopamine receptors. Such a mechanism may be significantly
      implicated during binge patterns of stimulant abuse and may also play a role in
      the sensitization associated with repeated amphetamine administration.

PMID- 9918579
TI  - Novel antipsychotic-like effects on prepulse inhibition of startle produced by a
      neurotensin agonist.
AB  - Agonists of the neuropeptide neurotensin have been proposed as potential novel
      antipsychotics based on their ability to modulate neurotransmission in brain
      regions associated with schizophrenia. To test this hypothesis, we examined the
      effects of a neurotensin mimetic with improved metabolic stability in an animal
      model with strong predictive validity for antipsychotic activity. Subcutaneous
      injections of PD149163, a reduced amide neurotensin(8-13) mimetic, significantly
      antagonized the reduction of prepulse inhibition (PPI) of the rat startle reflex
      produced by amphetamine and by the phencyclidine analog dizocilpine. PD149163 had
      no significant effect on baseline PPI or on baseline startle amplitude and did
      not antagonize the reduction of PPI produced by the direct dopamine agonist
      apomorphine. These findings suggest that PD149163 has novel antipsychotic-like
      properties that are distinct from known members of both the "typical" and
      "atypical" families of antipsychotics.

PMID- 9918580
TI  - Lead stimulates lymphocyte proliferation through enhanced T cell-B cell
      interaction.
AB  - We have studied the in vitro effects of lead (Pb) as Pb-acetate (0. 1-1000 ppm)
      on the activation of rat spleen (SP) cells. At a concentration of 0.5 to 200 ppm,
      Pb augmented the uptake of [3H]thymidine, progression of SP cells through the
      cell cycle, and allogeneic and syngeneic mixed lymphocyte reactions. However, at
      concentrations above 200 ppm, Pb inhibited the proliferation of these cells. To
      understand the cellular and molecular basis of these responses, we examined the
      effects of Pb on the proliferation of isolated T and/or B cell populations. Pb
      failed to stimulate the proliferation of isolated T and B cells; however, the
      addition of gamma-irradiated B cells to T cell cultures or irradiated T cells to
      B cell cultures resulted in Pb-induced incorporation of [3H]thymidine. On the
      other hand, macrophages were unable to reconstitute this response. Pb also
      induced a significant rise in the intracellular concentration of inositol 1,4,5
      trisphosphate in SP cells; however, unlike the activation of lymphocytes through
      the antigen receptors, Pb did not significantly stimulate protein tyrosine kinase
      activity. These observations suggest that Pb facilitates the T cell-B cell
      interaction-dependent proliferation of lymphocytes through a signaling pathway(s)
      independent of the antigen receptor.

PMID- 9918581
TI  - Pharmacokinetic/Pharmacodynamic models for corticosteroid receptor down
      regulation and glutamine synthetase induction in rat skeletal muscle by a
      Receptor/Gene-mediated mechanism.
AB  - Muscle wasting and excessive fat deposition are side effects attendant to chronic
      corticosteroid treatment. Corticosteroid immunosuppression is necessary in
      circumstances such as transplantation. Pharmacokinetic/pharmacodynamic (PK/PD)
      modeling was used to help elucidate the relationships between the events in the
      molecular cascade that result in muscle wasting and fat deposition by
      corticosteroids. Specifically, the relationships for receptor/gene-mediated
      effects that result in increased glutamine synthetase (GS) activity in skeletal
      muscle were quantitatively analyzed after an i.v. bolus dose of 50 mg/kg
      methylprednisolone in male adrenalectomized Wistar rats. Profiles of
      methylprednisolone pharmacokinetics, glucocorticoid receptor density, and its
      mRNA, GS mRNA, and GS activity in gastrocnemius muscles were determined. The
      results were used to develop PK/PD models using differential equations in the
      ADAPT II program. Two indirect response models were tested for the dynamics of
      glucocorticoid receptor mRNA regulation by activated steroid/receptor complex.
      Both reduction in message synthesis and message destabilization may be involved
      but with some tissue specificity. The recovery of active receptor after down
      regulation is biphasic. The initial recovery may involve receptor recycling from
      the nucleus, whereas the later phase may involve de novo synthesis of new
      receptor protein. The nuclear events and GS mRNA/GS induction in rat skeletal
      muscle show sequential relationships for each component for corticosteroid
      actions. The PK/PD models provide mechanism-based methods of quantifying complex
      processes in receptor/gene-mediated enzyme induction featuring the
      characteristics of time delay and possible nonlinearity in intact tissues.

PMID- 9918582
TI  - Comparison of an agonist, urocortin, and an antagonist, astressin, as
      radioligands for characterization of corticotropin-releasing factor receptors.
AB  - The characteristics of a high-affinity antagonist radioligand are compared with
      those a high-affinity agonist in binding to the cloned corticotropin-releasing
      factor receptor type 1 (CRF-R1) and type 2 (CRF-R2) and to the native receptors
      that exist in rat cerebellum and brain stem. The relative potencies of CRF
      antagonists and agonists to the two types of cloned CRF receptors overexpressed
      stably in Chinese hamster ovary cells are determined using the antagonist
      radioligand 125I- [DTyr1]astressin (Ast*), and the agonist radioligand, 125I 
      [Tyr0]rat urocortin (Ucn*). The inhibitory binding constants (Ki) of astressin
      and urocortin are 1 to 2 nM for all receptors and are independent of which
      radioligand is employed. Astressin binds with high affinity to the native
      cerebellar/brain stem receptor and relative potencies of selected CRF analogs
      determined with Ast* on the native receptor are similar to those obtained for the
      cloned CRF-R1. The specific binding of Ast* to endogenous brain receptors is
      greater than that of Ucn*, resulting in more sites being detected by the
      antagonist than by the agonist. In contrast to another CRF agonist, the binding
      of Ucn* to the cloned receptors is relatively insensitive to guanyl nucleotides
      at both 20 degreesC and 37 degreesC; however, its binding to the native receptor
      is displaced by guanyl nucleotides at 37 degreesC and, to a lesser degree, at 20
      degreesC. As expected, the binding of the antagonist Ast* is not affected by
      guanyl nucleotides. Because it is a high-affinity, specific CRF antagonist,
      astressin is eminently suitable as a ligand for detection and characterization of
      both endogenous and cloned CRF receptors.

PMID- 9918583
TI  - Active efflux of CPT-11 and its metabolites in human KB-derived cell lines.
AB  - To investigate the possible involvement of P-glycoprotein (P-gp), multidrug
      resistance-associated protein (MRP), and/or other glutathione S-conjugate export
      pump (GS-X pump) family members on the active efflux of irinotecan [(7-ethyl-10
      [4-(1-piperidino)-1-pipertidino)-1-piperidino]carb onylox y camptothecin (CPT
      11)] and its metabolites, as well as their contribution to the acquisition of
      resistance, we studied the uptake of CPT-11, its active metabolite SN-38, and
      glucuronide conjugate (SN38-Glu) using membrane vesicles from human epidermoid KB
      3-1-derived cell lines. These lines included KB-C2, C-A500, and KCP-4, which
      overexpress P-gp, MRP, and the unidentified GS-X pump, respectively. The
      carboxylate form of SN-38 exhibited significant ATP-dependent transport, with a
      Michaelis constant of 17 microM, into membrane vesicles from C-A500 but not from
      other cell lines. Among these KB-derived cells, significant ATP-dependent uptake
      of the carboxylate form of CPT-11 was only observed in KB-C2 vesicles. In
      addition, the uptake of the lactone and carboxylate forms of SN38-Glu into
      membrane vesicles from C-A500 and KB-C2, but not KCP-4, was ATP dependent,
      although the transport activity in C-A500 was much higher than that in KB-C2. The
      3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay
      revealed that the resistance of KB-C2 to CPT-11 and SN-38, compared with that of
      KB-3-1, was 6.3- and 6.8-fold, respectively; the corresponding figures for C-A500
      were 12- and 27-fold, respectively, whereas those for KCP-4 were 2.3- and 20
      fold, respectively. These results suggest that MRP and P-gp are involved in the
      active efflux of SN-38 and CPT-11, respectively, from human KB-derived cells. In
      addition, a difference in substrate specificity among GS-X pump members was
      demonstrated.

PMID- 9918584
TI  - Kinin-mediated coronary nitric oxide production contributes to the therapeutic
      action of angiotensin-converting enzyme and neutral endopeptidase inhibitors and
      amlodipine in the treatment in heart failure.
AB  - Increasing evidence suggests that angiotensin-converting enzyme (ACE) inhibitors
      can increase vascular nitric oxide (NO) production. Recent studies have found
      that combined inhibition of ACE and neutral endopeptidase (NEP) may have a
      greater beneficial effect in the treatment of heart failure than inhibition of
      ACE alone. Amlodipine, a calcium channel antagonist, has also been reported to
      have a favorable effect in the treatment of patients with cardiac dysfunction.
      The purpose of this study was to determine whether and the extent to which all of
      these agents used in the treatment of heart failure stimulate vascular NO
      production. Heart failure was induced by rapid ventricular pacing in conscious
      dogs. Coronary microvessels were isolated from normal and failing dog hearts.
      Nitrite, the stable metabolite of NO, was measured by the Griess reaction. ACE
      and NEP inhibitors and amlodipine significantly increased nitrite production from
      coronary microvessels in both normal and failing dog hearts. However, nitrite
      release was reduced after heart failure. For instance, the highest concentration
      of enalaprilat, thiorphan, and amlodipine increased nitrite release from 85 +/- 4
      to 156 +/- 9, 82 +/- 7 to 139 +/- 8, and 74 +/- 4 to 134 +/-10 pmol/mg (all *p
      <.01 versus control), respectively, in normal dog hearts. Nitrite release in
      response to the highest concentration of these two inhibitors and amlodipine was
      reduced by 41% and 31% and 32% (all #p <.01 versus normal), respectively, in
      microvessels after heart failure. The increase in nitrite induced by either ACE
      or NEP inhibitors or amlodipine was entirely abolished by Nw-nitro-L-arginine
      methyl ester, HOE 140 (a B2-kinin receptor antagonist), and dichloroisocoumarin
      (a serine protease inhibitor) in both groups. Our results indicate that: 1) there
      is an impaired endothelial NO production after pacing-induced heart failure; 2)
      both ACE and NEP are largely responsible for the metabolism of kinins and
      modulate canine coronary NO production in normal and failing heart; and 3)
      amlodipine releases NO even after heart failure and this may be partly
      responsible for the favorable effect of amlodipine in the treatment of heart
      failure. Thus, the restoration of reduced coronary vascular NO production may
      contribute to the beneficial effects of these agents in the treatment of heart
      failure.

PMID- 9918585
TI  - l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo
      deprenyl-derived l-methamphetamine.
AB  - This study evaluated whether the caudate-putamen dopamine response that has been
      observed after deprenyl administration could be attributed exclusively to
      metabolically generated l-methamphetamine (l-MeAmp). Brain and plasma levels of
      deprenyl and l-MeAmp were measured after deprenyl (10 mg/kg s.c.) from 10 to 60
      min in conscious rats. Peak caudate-putamen levels were observed for deprenyl (15
      nmol/g) at 10 min and for l-MeAmp (3 nmol/g) at 30 min. In a parallel study, l
      MeAmp metabolism was evaluated. After l-MeAmp (20 mg/kg s.c.), metabolite levels
      remained low relative to those of the parent compound: l-amphetamine,
      approximately 5 to 12%; and para-hydroxy-l-methamphetamine (OH-MeAmp),
      approximately 0.25%. Accordingly, l-MeAmp was considered to be the primary
      pharmacologically active deprenyl metabolite. A pharmacokinetic-pharmacodynamic
      analysis was then used to relate these pharmacokinetic data to the results of
      previous microdialysis studies in which increases in extracellular dopamine were
      measured in the caudate-putamen after l-MeAmp (3-18 mg/kg) and after deprenyl (10
      mg/kg). Dopamine response-area under curve versus dose plots were generated and
      used to show that an administered dose of 4 mg/kg l-MeAmp would be necessary to
      effect a dopamine response-area under curve comparable to that observed after the
      deprenyl dose. However, the present pharmacokinetic results indicated that l
      MeAmp brain levels after deprenyl corresponded to those that would be obtained
      from 0.4 mg/kg l-MeAmp (i.e., one tenth of the required dose). Collectively,
      these results suggest that the acute increases in extracellular dopamine observed
      after deprenyl are not due uniquely to metabolically generated l-MeAmp but also
      to other actions of deprenyl at the dopamine terminal.

PMID- 9918586
TI  - Chelation of zinc in the extracellular area of the spinal cord, using
      ethylenediaminetetraacetic acid disodium-calcium salt or dipicolinic acid,
      inhibits the antinociceptive effect of capsaicin in adult mice.
AB  - Capsaicin depolarizes primary afferent C-fibers releasing substance P (SP) whose
      N-terminal metabolites appear to play a role in the development of
      antinociception. Because some effects of SP(1-7) are similar to those of zinc, we
      tested the hypothesis that zinc in the extracellular area plays a role in
      capsaicin-induced antinociception, as measured using the abdominal stretch
      (writhing) assay. Decreases in zinc were achieved by intrathecal (i.t.) injection
      of membrane-impermeable compounds: ethylenediaminetetraacetic acid disodium
      calcium salt (Ca++ EDTA), a calcium-saturated chelator of divalent cations, or
      dipicolinic acid, a zinc chelator. Ten nanomoles of Ca++ EDTA had no effect on
      writhing at either 90 min or 24 h after injection, yet pretreatment with Ca++
      EDTA prevented the development of antinociception 24 h after i.t. injection of
      either 2. 8 nmol of capsaicin or 10 nmol of SP(1-7). One nanomole of dipicolinic
      acid injected i.t. also blocked capsaicin- and SP(1-7)-induced antinociception.
      When injected 24 h after SP(1-7), Ca++ EDTA failed to reverse antinociception.
      Acute antinociception produced 30 min after injection of SP(1-7) was also blocked
      when Ca++ EDTA was injected 24 h, but not 60 min, before SP(1-7). Thus, the
      optimal time of Ca++ EDTA-induced hyperalgesia (90 min), described previously,
      did not correspond to that of its inhibitory effect on antinociception (24 h). In
      contrast, we found that the previously described antinociception after an i.t.
      injection of zinc (90 min) is greatly attenuated by 24 h. Thus, zinc appears to
      be necessary, but may not be sufficient, for the long-term antinociceptive effect
      of capsaicin, acting downstream from the action of substance P N-terminal
      metabolites.

PMID- 9918587
TI  - Trauma decreases leucine enkephalin hydrolysis in human plasma.
AB  - Plasma hydrolysis of leucine enkephalin was evaluated, together with several
      cellular immune parameters, in a homogeneous group of human subjects who had
      undergone severe trauma (proximal femur fracture); data obtained were compared
      with those obtained in an age-matched control group. In the experimental group,
      immediately after hospitalization, substrate hydrolysis was reduced with respect
      both to the control subjects and the same patients 4 weeks after the trauma.
      Chromatographic separation of the enzymes active on leu-enkephalin showed that
      the reduction of substrate hydrolysis is mainly attributable to the decrease in
      the activity of enkephalin-degrading enzymes, principally of aminopeptidases, per
      se, whereas the role of the low-molecular-weight plasma inhibitors is only minor.
      In the same subjects, several of the immunological parameters measured underwent
      modifications that may be considered stress related. However, the absence of a
      quantitative relationship between reduction in hydrolysis and modifications of
      immune parameters does not support the hypothesis of a direct relationship
      between these two sets of data.

PMID- 9918588
TI  - Effects of antipsychotic drugs on extracellular dopamine levels in rat medial
      prefrontal cortex and nucleus accumbens.
AB  - The present study was designed to compare the effects of typical and atypical
      antipsychotic drugs on extracellular dopamine (DA) levels in the medial
      prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo
      microdialysis with dual probe implantation in awake, freely moving rats.
      Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10
      mg/kg), all of which are atypical antipsychotics, produced greater increases in
      extracellular DA levels in the mPFC than in the NAC. Olanzapine (1 mg/kg),
      risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, and S-(-)
      sulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in
      extracellular DA levels in the mPFC and the NAC. S-(-)-sulpiride (10 mg/kg) and
      haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, significantly
      increased extracellular DA levels in the NAC but not in the mPFC. The effects of
      the six antipsychotic drugs to increase extracellular DA levels in the mPFC
      relative to those in the NAC was positively correlated with the difference
      between their pKi values for serotonin (5-hydroxytryptamine, 5-HT2A) and DA-D2
      receptors and was inversely correlated to their pKi values for D2 or D3
      receptors, but was not for 5-HT2A receptors alone. These results are consistent
      with the hypothesis that the ability of antipsychotic drugs to produce a greater
      increase in prefrontal compared with NAC extracellular DA levels may be related,
      in part, to weak D2 and D3 receptor affinity relative to 5-HT2A receptor
      antagonism.

PMID- 9918589
TI  - Chronic ethanol differentially alters susceptibility to chemically induced
      convulsions in withdrawal seizure-prone and -resistant mice.
AB  - Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were
      selectively bred to have severe (WSP) or mild (WSR) handling-induced convulsions
      after chronic ethanol inhalation. The purpose of the present experiments was to
      determine whether seizure susceptibility differences between WSP and WSR mice
      during ethanol withdrawal were specific to agents acting at gamma-aminobutyric
      acidA or excitatory amino acid (EAA) receptors. Male WSP and WSR mice were
      exposed to ethanol vapor or air for 24 or 72 h. During peak withdrawal (i.e.,
      between 6.5 and 8 h after removal from the inhalation chambers), separate groups
      of animals were administered pentylenetetrazol, (+)bicuculline, N-methyl-D
      aspartate, kainic acid, or strychnine via timed tail vein infusion. Withdrawal
      from ethanol significantly increased sensitivity to pentylenetetrazol and
      (+)bicuculline versus air-exposed WSP and WSR mice. In contrast, sensitivity to N
      methyl-D-aspartate-induced convulsions was significantly decreased in the ethanol
      exposed WSR and unchanged in the ethanol-exposed WSP mice. Sensitivity to kainic
      acid was significantly increased in both ethanol-exposed WSR and WSP mice,
      although the magnitude of change in sensitivity was greater in the ethanol
      withdrawing WSP line. Interestingly, sensitivity to strychnine was decreased
      similarly in the ethanol-exposed WSP and WSR mice, compared with their respective
      air-exposed animals. These results suggest that chronic ethanol increased
      sensitivity to convulsants active at gamma-aminobutyric acidA receptors similarly
      in WSP and WSR mice, but differentially changed sensitivity to convulsants active
      at EAA receptors in the lines. This supports a role for EAA systems in
      determining genetic susceptibility to alcohol withdrawal.

PMID- 9918590
TI  - Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486).
AB  - Mifepristone (RU486), an 11beta-substituted nor-steroid containing a 17alpha-1
      propynyl group used clinically as an antiprogestin agent for medical abortions,
      was demonstrated to be a selective mechanism-based inactivator of human
      cytochrome P-450-3A4 (CYP-3A4). The loss of testosterone 6beta-hydroxylation
      activity was time- and concentration-dependent as well as requiring metabolism of
      mifepristone in a purified CYP-3A4 reconstituted system. The inactivation
      exhibited pseudofirst-order kinetics. The values for KI and kinactivation were
      4.7 microM and 0.089 min-1, respectively. The reduced-CO spectrum of CYP-3A4 was
      decreased by 76%, whereas approximately 81% of the activity was lost following
      incubation with mifepristone in the reconstituted system in the presence of
      NADPH. However, the Soret peak of the inactivated CYP-3A4 was slightly increased.
      High-performance liquid chromatography analysis of the incubation mixture showed
      that the peak containing the heme dissociated from the inactivated CYP3A4 was
      almost identical with that seen for the -NADPH control. Covalent binding of
      [3H]mifepristone to apoCYP3A4 was demonstrated by SDS-PAGE and high-pressure
      liquid chromatography analyses of the reconstituted system containing CYP-3A4,
      NADPH-CYP reductase, cytochrome b5 and lipids in the presence of NADPH. The
      stoichiometry was determined to be approximately 1 mol of mifepristone bound per
      1 mol of CYP-3A4 inactivated. Therefore, the mechanism of inactivation of CYP-3A4
      by mifepristone involves irreversible modification of the apoprotein at the
      enzyme active site instead of being the result of heme adduct formation or heme
      fragmentation. Mifepristone exhibits selectivity for CYP-3A4 as evidenced by the
      fact that it did not show mechanism-based inactivation of CYPs 1A, 2B, 2D6, and
      2E1, although a competitive inhibition of CYP 2B1 and 2D6 was observed.

PMID- 9918591
TI  - Effects of alpha-2 adrenoceptor agonists and antagonists on circling behavior in
      rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway.
AB  - The present study examined the influence of alpha-2 adrenoceptor ligands on
      circling behavior in rats with unilateral 6-hydroxydopamine lesions of the
      nigrostriatal pathway. The alpha-2 adrenoceptor agonists, clonidine and UK 14304,
      inhibited both the ipsilateral rotation induced by the indirect dopaminergic
      agonist, methylphenidate, and the contralateral circling induced by the direct
      dopaminergic agonist, apomorphine. In contrast, the alpha-2 adrenoceptor
      antagonists, idazoxan and (+/-)-efaroxan, enhanced the circling induced by either
      methylphenidate or apomorphine. The facilitating activity of efaroxan was
      stereoselective because the (+)-enantiomer mimicked the effect of (+/-)-efaroxan,
      whereas the (-)-enantiomer was essentially inactive, thus indicating a mediation
      by alpha-2 adrenoceptors. Upon administration alone, the above-mentioned
      compounds did not modify spontaneous circling behavior, except for UK 14304,
      which decreased, and (+)-efaroxan, which slightly increased, the ipsilateral
      rotation. We conclude that activation and antagonism of alpha-2 adrenoceptors
      inhibit and enhance, respectively, the circling behavior evoked by both direct
      and indirect dopaminergic agonists. Although a modulation of dopamine release may
      be involved in some of these drug effects, the effects on apomorphine-induced
      circling indicate an influence of alpha-2 adrenoceptor compounds on nigrostriatal
      neurotransmission at sites downstream from the dopaminergic neurons themselves.
      These findings support the notion of a potential benefit of alpha-2 adrenoceptor
      antagonists in the treatment of Parkinson's disease.

PMID- 9918592
TI  - Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal
      cardiac preparations.
AB  - Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse
      physiological effects in animal systems. However, the effects of AP4A on inotropy
      in ventricular cardiac preparations have not yet been studied. The effects of
      AP4A on force of contraction (FOC) were studied in isolated electrically driven
      guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L
      type calcium current and [Ca]i were studied in isolated guinea pig ventricular
      myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally
      by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was
      ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%.
      The negative inotropic effects of AP4A in atria and papillary muscles were
      abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl
      cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM)
      attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human
      atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to
      158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic
      effects were abolished by the P2-purinoceptor antagonist suramin. On the other
      hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated
      human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl
      cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts
      negative inotropic effects in animal and human ventricular preparations via
      stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive
      inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2
      purinoceptor stimulation might be a new positive inotropic principle in the human
      myocardium.

PMID- 9918593
TI  - Improving effects of huperzine A on spatial working memory in aged monkeys and
      young adult monkeys with experimental cognitive impairment.
AB  - Our previous studies demonstrated that huperzine A, a reversible and selective
      acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in
      various rodent models of amnesia. To extend the antiamnesic action of huperzine A
      to nonhuman primates, huperzine A was evaluated for its ability to reverse the
      deficits in spatial memory produced by scopolamine in young adult monkeys or
      those that are naturally occurring in aged monkeys using a delayed-response task.
      Scopolamine, a muscarinic receptor antagonist, dose dependently impaired
      performance with the highest dose (0.03 mg/kg, i.m.) producing a significant
      reduction in choice accuracy in young adult monkeys. The delayed performance
      changed from an average of 26.8/30 trials correct on saline control to an average
      of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.
      1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young
      adult monkeys on a delayed-response task; performance after an optimal dose (0.1
      mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01
      mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline
      control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01
      mg/kg for the other two monkeys). The beneficial effects of huperzine A on
      delayed-response performance were long lasting; monkeys remained improved for
      about 24 h after a single injection of huperzine A. This study extended the
      findings that huperzine A improves the mnemonic performance requiring working
      memory in monkeys, and suggests that huperzine A may be a promising agent for
      clinical therapy of cognitive impairments in patients with Alzheimer's disease.

PMID- 9918594
TI  - Electrophysiological comparison of 5-Hydroxytryptamine1A receptor antagonists on
      dorsal raphe cell firing.
AB  - Single-unit recording studies were undertaken in chloral hydrate-anesthetized
      rats to compare the effects on dorsal raphe cell firing of several putative 5
      hydroxytryptamine (HT)1A receptor antagonists, including WAY 100635 (N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide), p
      MPPI (4-(2-methoxyphenyl)1-[2'-[N-(2"-pyridinyl)-p-iodobenzamido]ethyl] pip
      erazine), and two newly described 5-HT1A receptor antagonists, NDL-249 [(R)-3-(N
      propylamino)-8-fluoro-3, 4-dihydro-2H-1-benzopyran-5-carboxamide] and NAD-299
      [(R)-3-N, N-dicyclobutylamino-8-fluoro-3, 4-dihydro-2H-1-benzopyran-5
      carboxamide]. Consistent with a 5-HT1A receptor antagonist profile, pretreatment
      with an approximately equimolar (0.02-0.03 micromol/kg) i.v. dose of each
      compound caused a significant rightward shift in the dose-response curve for 8-OH
      DPAT [8-hydroxy-2-(di-n-propylamino)tetralin]. Antagonist potency was clearly
      highest for NAD-299 and WAY 100635, which caused shifts roughly 3 times greater
      than those for either p-MPPI or NDL-249 (ED50 for 8-OH-DPAT, 1.3 +/- 0.3
      microg/kg; after NAD-299, 18.2 +/- 1.0 microg/kg; after WAY 100635, 16.9 +/- 2.9
      microg/kg; after NDL-249, 6.0 +/- 1.2 microg/kg; after p-MPPI, 4.7 +/- 1.1
      microg/kg). In separate studies, each of the antagonists was administered alone
      in increasing cumulative doses to evaluate whether they possessed intrinsic
      agonist activity in this system. At doses below 0.01 micromol/kg, none of the
      drugs altered firing by more than +/-20% basal rates. At higher doses (>0.1
      micromol/kg), WAY 100635, NDL-249, and NAD-299 caused a dose-dependent
      suppression of dorsal raphe cell firing (ED50 = 0.6 +/- 0.2, 0.7 +/- 0.3, and 0.
      9 +/- 0.4 micromol/kg, respectively). However, the ED50 values for inhibition by
      these drugs were roughly 30 times higher than the doses that antagonized effects
      of 8-OH-DPAT. Moreover, the inhibition by all three antagonists (but not 8-OH
      DPAT) was readily reversed by d-amphetamine (3.2 mg/kg i.v.), a releaser of
      norepinephrine, suggesting that these effects were likely due to alpha adrenergic
      receptor blockade rather than to 5-HT1A receptor agonism. Thus, it was concluded
      that WAY 100635, NAD-299, NDL-249, and p-MPPI all fulfill criteria as 5-HT1A
      receptor antagonists lacking intrinsic efficacy in the dorsal raphe system. The
      newly described compound NAD-299 exhibits antagonist potency comparable to that
      of WAY 100635 in this electrophysiological assay.

PMID- 9918595
TI  - Opioid efficacy in a C6 glioma cell line stably expressing the human kappa opioid
      receptor.
AB  - A C6 glioma cell line stably transfected with the human kappa opioid receptor
      (kappaOR) was used to characterize receptor binding and G protein activation via
      the kappaOR by a comprehensive series of opioid ligands. The ligand-binding
      affinity for [3H]5alpha,7alpha, 8beta(-)-N-methyl-N-(7-Cl-pyrrolidinyl)-1
      oxaspiro(4, 5)dec-8-yl)benzene acetamide (U69593) was similar to that observed in
      monkey brain membranes and was 10-fold lower in the presence of sodium and GDP.
      Both peptide and nonpeptide agonists maximally stimulated [35S]GTPgammaS binding.
      The stimulation of [35S]GTPgammaS binding was blocked by pretreatment of cells
      with pertussis toxin. Partial stimulation of [35S]GTPgammaS binding via the
      kappaOR was observed for several ligands that are antagonists at the mu opioid
      receptor, suggesting an additional mechanism of drug action. The ability of
      isomers of tifluadom and levallorphan to stimulate [35S]GTPgammaS binding
      indicates that the chiral carbon of levallorphan, a benzomorphan derivative,
      imparts a greater degree of stereoselectivity than does the chiral carbon in the
      benzodiazepine derivative tifluadom. In addition, (-)tifluadom, the less potent
      isomer of tifluadom, which is also a gamma-aminobutyric acidA receptor agonist,
      stimulated [35S]GTPgammaS binding. In contrast, d-pentazocine, (+)SKF10047,
      (+)cyclazocine, and d-ethylketocyclazocine displayed no agonist activity. kappaOR
      selective antagonist norbinaltorphimine competitively inhibited the stimulation
      of [35S]GTPgammaS binding by the active isomers of ethylketocyclazocine,
      cyclazocine, and nalorphine to the same degree, indicating that all three ligands
      are eliciting an effect via the kappaOR. The results suggest that these cells
      express a homogeneous population of kappaOR, and that their [35S]GTPgammaS
      binding properties make them an excellent means to assess kappaOR efficacy.

PMID- 9918596
TI  - Identification of a novel, inhibitory action of amiodarone on vesicular monoamine
      transport.
AB  - The benzofuran antiarrhythmic drug, amiodarone, exhibits a wide range of
      pharmacological properties. Recent in vivo biochemical studies suggest that
      amiodarone may exert an antiadrenergic action in the heart, which resembles the
      effects of reserpine. To investigate the cellular basis for this apparent
      presynaptic, sympatholytic action we used Chinese hamster ovary (CHO) cells
      expressing the type 2 vesicular monoamine transporter (VMAT2) as a synaptic
      vesicular model. Amiodarone inhibited the uptake of [3H]norepinephrine in VMAT2
      transfected CHO cells in a concentration-dependent manner, with a -log EC50 of
      6.44 +/- 0.32. To further identify the site at which amiodarone suppressed
      vesicular monoamine transport, we examined the ability of amiodarone to displace
      [3H]reserpine from its binding site in membrane fractions prepared from CHO cells
      expressing VMAT2. [3H]Reserpine binding was inhibited in a concentration
      dependent manner by amiodarone, with an -log EC50 of 6.76 +/- 0.03, reaching 84
      +/- 5% inhibition of reserpine binding at 10 microM. A pH-dependent mechanism for
      this action of amiodarone was excluded in studies using the pH-sensitive
      fluorescent indicator 2',7'-bis (carboxyethyl)-5,6-carboxyfluorescein (BCECF).
      These data indicate that amiodarone inhibits the uptake of monoamine into the
      axoplasmic storage vesicle by inhibiting VMAT. Furthermore, amiodarone competes
      specifically with reserpine for binding to VMAT. These findings suggest a novel
      presynaptic site of action for amiodarone.

PMID- 9918597
TI  - Timolol effects on aqueous humor dynamics in eyes of anesthetized rats.
AB  - Anterior chambers of the eyes of male rats were cannulated under pentobarbital
      anesthesia for intracameral infusions of balanced salt solution (BSS) and
      intraocular pressure (IOP) recording. Blood pressure was recorded from a femoral
      artery. IOP was recorded during a 2-h intracameral infusion composed of a
      constant component (0.05 microl/min) and a periodic component (0.25 microl/min),
      cycling at 4 min on and then 4 min off. After a 20-min baseline period, 1 drop of
      timolol (0.5%) or BSS was applied to the cornea and repeated 1 h later.
      Intracameral infusions of BSS and 0.05% timolol were also compared. Topical
      timolol slightly delayed the BSS-induced IOP rise (p <.05). Complex demodulation
      and the estimated gain parameter of a second-order transfer function fit to the
      periodic responses revealed that topical timolol also reduced (p <.05) passive
      outflow resistance. Intracameral timolol markedly delayed the BSS-induced rise in
      IOP. Initially, timolol decreased both outflow impedance and nonresistive
      components (p <.05) of IOP, but these effects dissipated by 2 h when IOPs were
      similar. In all experiments, within-group blood pressure was unchanged. Topical
      and intracameral timolol have different effects on IOP. The data support the
      opinion that, in vivo, timolol acts at beta-receptors that control both outflow
      impedance and nonresistive mechanisms, probably vascular, to lower IOP.

PMID- 9918598
TI  - Anxiolytic 5-hydroxytryptamine1A agonists suppress firing activity of dorsal
      hippocampus CA1 pyramidal neurons through a postsynaptic mechanism: single-unit
      study in unanesthetized, unrestrained rats.
AB  - Recent behavioral studies indicate that conditioned fear response to contextual
      stimuli is reduced effectively by anxiolytic 5-hydroxytryptame (5-HT)1A agonists.
      Since the hippocampus seems to play an essential role in associative fear
      memories evoked by context, it is important to assess the effect of 5-HT1A
      agonists on pyramidal cell activity in the hippocampus. We examined the effects
      of 5-HT1A agonists on the spontaneous firing rate of hippocampal CA1 pyramidal
      neurons in unanesthetized, unrestrained rats. Systemic administration of
      selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone,
      ipsapirone, and flesinoxan produced a dose-dependent inhibition of neuronal
      activity. Putative 5-HT1A antagonists NAN-190 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]piperazine and (-)-pindolol did not change neuronal activity of
      CA1 pyramidal neurons. The suppression of neuronal activity by buspirone was
      antagonized by NAN-190 but not by (-)-pindolol. Lack of antagonistic activity of
      (-)-pindolol for the suppression of pyramidal neurons via a postsynaptic
      mechanism is consistent with the results of recent electrophysiological
      experiments in anesthetized rats. Pretreatment with parachlorphenylalanine did
      not change the spontaneous firing rates of hippocampal CA1 pyramidal neurons or
      abolish the suppressant effects of buspirone on these neurons. Taken together,
      the present results strongly suggest that suppression of the hippocampal CA1
      pyramidal neuronal activity by anxiolytic 5-HT1A agonists in awake rats is
      mediated by postsynaptic 5-HT1A receptors located on pyramidal neurons.

PMID- 9918599
TI  - Oral administration of leflunomide (HWA486) results in prominent suppression of
      immunoglobulin E formation in a rat type 1 allergy model.
AB  - Leflunomide, a drug being developed for use in the treatment of rheumatoid
      arthritis, was evaluated in an ovalbumin (OVA)-induced rat type 1 allergy model.
      In a dose of 1 mg/kg/day, it strongly suppressed the formation of OVA-specific
      IgE, thus preventing the elevation of the plasma histamine level and induction of
      anaphylactic shock observed after i.v. challenge with OVA. Studies on
      leflunomide's effects on the secondary antibody response showed that
      administration during the primary immune response remarkably diminished the
      secondary antibody responses, except IgM, even without further drug
      administration. Furthermore, when administered during the secondary response
      after rechallenge, both the total IgE and OVA-specific IgE serum levels declined
      rapidly to nearly baseline levels. Although OVA-specific IgG1, IgG2a, and IgM did
      not decrease from their primary response levels, these classes' secondary
      responses were strongly suppressed. In an in vitro study, the proliferation and
      antibody production of OVA-stimulated spleen cells, derived from Brown Norway
      rats, were strongly inhibited by A77 1726, leflunomide's active metabolite. When
      uridine was added to the cell culture, this molecule's effect on cell
      proliferation was completely restored, whereas the antibody production was
      partially restored. These findings are consistent with data indicating that
      leflunomide is a dihydroorotate dehydrogenase inhibitor. Taken together, the
      above findings suggest the therapeutic potential of leflunomide against type 1
      allergic diseases.

PMID- 9918600
TI  - Block of potassium currents in guinea pig ventricular myocytes and lengthening of
      cardiac repolarization in man by the histamine H1 receptor antagonist
      diphenhydramine.
AB  - Treatment with second generation histamine H1 receptor antagonists has been
      associated with lengthening of the Q-T interval and proarrhythmia. Similarly,
      lengthening of the Q-T interval has been reported in patients after overdosing
      with diphenhydramine (DPH), a first generation agent. Therefore, our study was
      designed 1) to assess effects of DPH on cardiac repolarization and 2) to
      characterize effects of the drug on major voltage-dependent cardiac K+ currents.
      First, we noticed that oral administration of DPH at usual dosages to healthy
      volunteers or to patients (prior to angioplasty) was associated with prolongation
      of the Q-Tc interval. Although this effect was modest in most individuals, Q-Tc
      was increased more than 20 ms in 7 of 20 patients. Second, we noticed that
      exposure of isolated guinea pig hearts to DPH 10(-5) M caused a lengthening of
      monophasic action potential duration. This effect was potentiated by the combined
      perfusion of other K+ channel blockers such as indapamide. Finally, experiments
      performed with the patch-clamp technique demonstrated unequivocal block of the
      rapid component of the delayed rectifier (IKr) by DPH; however, IC50 determined
      for block of IKr (3 x 10(-5) M) is approximately 40-fold greater than plasma
      concentrations of the drug measured at usual dosages (7 x 10(-7) M).
      Consequently, in agreement with the long-term clinical use of the drug,
      prolongation of cardiac repolarization should be minimal in most patients at
      usual dosages but may be observed with overdosing. Nevertheless, caution remains
      since excessive lengthening of cardiac repolarization may occur after
      administration of DPH with other drugs due to 1) concomitant block of other ionic
      currents or 2) pharmacokinetic interactions leading to toxic concentrations of
      DPH.

PMID- 9918601
TI  - Potential role of the gene transcription factor cyclic AMP-responsive element
      binding protein in ethanol withdrawal-related anxiety.
AB  - This investigation examined the effects of acute and chronic ethanol exposure and
      its withdrawal on the cAMP-responsive element binding protein (CREB) and the
      activator protein-1 (AP-1) gene transcription factors in the rat brain. The
      anxiogenic effects of ethanol withdrawal after acute or protracted ethanol
      treatment of rats were measured by the elevated plus-maze (EPM) test. It was
      observed that ethanol withdrawal after acute ethanol treatment has no effect on
      open-arm activity (percent of open-arm entries and the mean percent of time spent
      on the open arms) of rats on the EPM test. On the other hand, the time course
      studies of the development of anxiety during ethanol withdrawal (0, 12, 24, and
      72 h) after 15 days of ethanol treatment indicate that peak anxiety (significant
      decrease in open-arm activity) occurred at 24 h of ethanol withdrawal in rats. It
      was observed that acute ethanol treatment and its withdrawal (24 h) had no effect
      on CRE- or AP-1 DNA-binding activities in the rat cortex as determined by the
      electrophoretic gel-mobility shift assay. It was also found that chronic ethanol
      treatment and its withdrawal (24 h) had no effect on AP-1 DNA-binding activity in
      the rat cortex. Investigation of the time course studies of changes in CRE-DNA
      binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after 15 days of
      ethanol treatment indicated that the peak reduction of CRE-DNA-binding activity
      occurred at 24 h of ethanol withdrawal. The changes in the immunolabeling of the
      CREB-related target, that is, brain-derived neurotrophic factor (BDNF), in the
      rat cortex during chronic ethanol treatment and its withdrawal (24 h) were
      examined using western blotting. It was found that 24 h but not 0 h of ethanol
      withdrawal after 15 days of ethanol treatment caused a significant decrease in
      the immunolabeling of BDNF in the rat cortex. Fluoxetine (alone) treatment of
      rats for 1 or 15 days had no effect on open-arm activity and cortical CRE-DNA
      binding activity. However, when fluoxetine was administered concurrently with
      ethanol treatment for 15 days, it caused a reversal of the anxiogenic effects of
      ethanol withdrawal and antagonized the down-regulation of CRE-DNA-binding
      activity and of the decrease in immunolabeling of BDNF in the cortices of ethanol
      withdrawn rats. On the other hand, acute fluoxetine treatment produced
      normalization of the reduction of cortical CRE-DNA binding in ethanol-withdrawn
      rats (24 h) but did not reach the level of significance compared with normal
      control rats. Acute fluoxetine treatment had no effect on anxiety in ethanol
      withdrawn rats. Taken together, these results suggest the possibility that
      decreased CRE-DNA-binding activity in the rat cortex may be associated with the
      molecular mechanisms of ethanol dependence (i.e., ethanol withdrawal-related
      anxiety).

PMID- 9918602
TI  - Age-related changes in the capacity, rate, and modulation of dopamine uptake
      within the striatum and nucleus accumbens of Fischer 344 rats: an in vivo
      electrochemical study.
AB  - Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake
      within the striatum and the nucleus accumbens core of Fischer 344 rats were
      investigated using in vivo electrochemical recordings coupled with local drug
      application techniques. Equimolar amounts of DA were pressure ejected into the
      striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA
      ejections produced larger DA signal amplitudes in the older rats, suggesting age
      related differences in the capacity to clear extracellular DA. Within the
      striatum, the capacity and rate of DA uptake were reduced by 50% in the aged
      groups (18 and 24 months) compared with the younger rats (6 and 12 months). In
      the nucleus accumbens, significant reductions in DA uptake capacity and rate were
      observed in the 24-month group. In both brain regions and in all age groups
      studied, the rate of DA uptake was found to be concentration-dependent until a
      maximal rate was reached. The maximum rate of DA transport was significantly
      reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24
      months versus 6 and 12 months). The ability of nomifensine, an inhibitor of the
      DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus
      accumbens was also decreased with age (24 months versus 6 months). Taken
      together, these findings demonstrate substantial age-related deficits in DA
      uptake processes within the striatum and the nucleus accumbens, consistent with
      the hypothesis that DA uptake may be slowed in aged animals to compensate for
      reductions in DA release.

PMID- 9918603
TI  - Specific renal delivery of sugar-modified low-molecular-weight peptides.
AB  - To develop a novel delivery system for peptides involving sugar modification, Arg
      vasopressin (AVP) was modified by linking it to a variety of sugars via an
      octamethylene group and the subsequent tissue uptake by rats was then monitored
      after administration by i.v. injection. The glucosyl, mannosyl, and 2
      deoxyglucosyl derivatives of AVP exhibited selective renal uptake. These
      derivatives were found to be distributed in the proximal tubules of the renal
      cortex. In addition, they exhibited specific binding to the kidney microsomal
      fraction in vitro (Kd = approximately 60 nM), suggesting that they are taken up
      by a specific recognition mechanism located in the kidneys. From the results of
      the uptake study of glucosyl derivatives, the following points are clear: 1)
      renal uptake in vivo becomes saturated with increasing dose, and the Km from the
      uptake study is almost the same as the Kd obtained in the binding assay in vitro
      and 2) because the renal first-pass uptake extraction is about 70% at a low dose
      (10 nmol/kg), there is an effective mechanism for uptake from blood. Furthermore,
      glucosyl and mannosyl derivatives of oxytocin, a neutral peptide, unlike AVP that
      is basic, also have high renal uptake clearances. Thus, the renal uptake may not
      be dependent on derivatives having a cationic nature. We conclude that there is a
      novel transport mechanism in the kidneys that can be used for the specific renal
      delivery of glycosylated peptides.

PMID- 9918604
TI  - Angiotensin II type 1 receptor blockade prevents up-regulation of angiotensin II
      type 1A receptors in rat injured artery.
AB  - We investigated the effects of the angiotensin II (Ang II) type 1 receptor (AT1)
      antagonist KRH-594 on levels of the mRNAs for AT1A, AT1B, platelet-derived growth
      factor-receptor beta (PDGF-Rbeta), and extracellular matrix (ECM)-related genes
      using the competitive reverse transcription-polymerase chain reaction (RT-PCR)
      method and on neointimal formation in the balloon-injured rat carotid artery. The
      mRNA levels for AT1A and PDGF-Rbeta, but not for AT1B, increased from day 3 after
      injury to day 14. KRH-594 administered orally at 3 and 10 mg/kg/day significantly
      suppressed these increases. KRH-594 (10 mg/kg/day) also suppressed the injury
      induced gene expressions for transforming growth factor-beta1 and fibronectin and
      reduced collagen alpha1(I) and alpha1(III) mRNA levels for the first 7 days after
      injury. KRH-594 (10 and 30 mg/kg/day) significantly and dose-dependently reduced
      the neointimal area in cross sections of the artery 14 days after injury. Another
      AT1 antagonist, TCV-116 (candesartan cilexetil; 1 and 3 mg/kg/day p.o.), had
      similar effects on the morphological change and AT1A mRNA level, whereas a smooth
      muscle relaxant, hydralazine (10 mg/kg/day p.o.), did not. These results indicate
      that up-regulation of AT1A, PDGF-Rbeta, and ECM-related genes in the balloon
      injured carotid artery is in part an AT1-mediated phenomenon and that prevention
      of receptor up-regulation may contribute to the attenuating effects of AT1
      antagonists on neointimal formation after injury.

PMID- 9918605
TI  - Hypothermia: a potential risk of CO2 insufflation?

PMID- 9918606
TI  - Humidified gas prevents hypothermia induced by laparoscopic insufflation: a
      randomized controlled study in a pig model.
AB  - BACKGROUND: This experimental study evaluated whether humidification of warmed
      insufflated CO2 during laparoscopic procedures would resolve the problem of
      laparoscopy-induced hypothermia. METHODS: Changes in core temperature were
      quantified over a 3-h period of high-flow CO2 insufflation in a randomized,
      controlled trial of five pigs. Each animal was anesthetized and studied on three
      occasions under standardized conditions, acting as its own control by
      insufflation with no gas compared with insufflation by cool dry gas and heated
      humidified gas. RESULTS: Core temperatures after insufflation with heated
      humidified gas were no different from that of controls. After insufflation with
      cool dry gas, core temperature dropped by 1.8 degreesC, which was significantly
      more than the 0.6 degreesC drop experienced by control animals and those
      insufflated with heated humidified gas (p < 0.01). Calculations of the heat
      expended in evaporation of water were also performed. The temperature drop due to
      water evaporation alone in pigs insufflated with cool dry gas was calculated to
      be 1.5 degreesC. This compares favorably with the measured 1.2 degreesC
      temperature difference between these animals and the control group. CONCLUSIONS:
      The majority of heat lost during laparoscopic insufflation is due to water
      evaporation, and laparoscopic hypothermia may be prevented by using heated and
      humidified gas insufflation.

PMID- 9918607
TI  - A randomized controlled trial assessing the benefit of humidified insufflation
      gas during laparoscopic surgery.
AB  - BACKGROUND: We conducted a randomized controlled trial during laparoscopic
      cholecystectomy to determine the extent of heat preservation and postoperative
      pain reduction using humidified carbon dioxide (CO2) gas insufflation instead of
      standard dry insufflation gas. METHODS: Forty consecutive patients were
      randomized. Twenty patients received humidified CO2, and 20 control patients
      received standard CO2 insufflation. A sample of 16 patients from each group was
      evaluated for postoperative pain levels. RESULTS: No adverse effects from the
      humidification of insufflated gas were observed. There was no significant
      difference in core body temperature between the two groups for this brief
      operation. Pain, as assessed by the Analogue Pain Score (APS) was significantly
      less for the group with humidified gas insufflation than for the control group at
      6 h postoperatively as well as on the 1st, 2nd, and 3rd postoperative day and at
      follow-up 10 days after the operation. In the humidified group, the mean time to
      return to normal activities was significantly less-5.9 days, as compared to 10.9
      days in the control group. CONCLUSIONS: The use of humidified insufflation gas
      reduces postoperative pain following laparoscopic cholecystectomy, but except for
      these relatively brief procedures, the heat-preserving effect of humidified gas
      insufflation is not significant.

PMID- 9918608
TI  - Laparoscopic exploration of the common bile duct: beyond the learning curve.
AB  - BACKGROUND: Bile duct clearance at open cholecystectomy had become normal
      surgical practice before the introduction of laparoscopic cholecystectomy.
      However, perceived technical difficulties have deterred many surgeons from
      treating common bile duct stones at the time of laparoscopic cholecystectomy.
      This has led to a reliance on preoperative clearance of ducts known to have
      stones and postoperative clearance of ducts found to have stones at operation or
      those that subsequently develop complications of retained stones. METHODS: The
      authors describe a series of 120 consecutive bile duct explorations carried out
      between April 1991 and February 1997 in a series of 1,237 laparoscopic
      cholecystectomies. RESULTS: Laparoscopic exploration and clearance of the bile
      ducts was achieved in 89% of cases in the whole series, and 97% success was
      attained in the last 60 cases, which also were associated with a decrease in
      operating time. CONCLUSIONS: We believe that for surgeons familiar with open
      common bile duct exploration and laparoscopic cholecystectomy, the next logical
      step is laparoscopic exploration of the common bile duct at the time of
      cholecystectomy, which is safe and readily mastered.

PMID- 9918609
TI  - Comparison of laparoscopic ultrasonography and fluorocholangiography in 300
      patients undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: This study compares laparoscopic ultrasonography to
      fluorocholangiography in detecting common bile duct (CBD) stones and delineating
      biliary anatomy. METHODS: A prospective nonrandomized study of 300 consecutive
      patients undergoing laparoscopic cholecystectomy in a university hospital was
      performed. After port placement but before dissection, laparoscopic
      ultrasonography of the extrahepatic CBD was performed in both transverse and
      longitudinal planes. Cystic duct fluorocholangiography was attempted in all
      patients. RESULTS: Of 300 patients, CBD stones were detected in 26 (9%) with 25
      of these (96%) detected on laparoscopic ultrasonography. Sonography identified
      the location and size of the CBD as well as anomalous anatomy prior to
      dissection. No CBD injuries were encountered. End-fire transducers were easier to
      use than rigid or flexible side-fire transducers; all gave excellent image
      quality. CONCLUSIONS: In this large study, laparoscopic ultrasonography and
      fluorocholangiography were equally sensitive in detecting CBD stones. Sonography
      delineates the biliary anatomy noninvasively and does not require dissection or
      opening of the biliary system. Laparoscopic ultrasonography may improve the
      safety of laparoscopic cholecystectomy, especially in cases of acute inflammation
      or distorted anatomy.

PMID- 9918610
TI  - Effectiveness of a hands-on training course for laparoscopic spine surgery in a
      porcine model.
AB  - BACKGROUND: Although it is widely proposed that surgeons, before introducing a
      novel laparoscopic technique in man, should practice in an appropriate animal
      model for acquisition of the necessary technical skills, the effectiveness of
      those hands-on training courses are rarely documented. METHODS: In 1995 we have
      organized eight hands-on training courses for laparoscopic anterior interbody
      spine fusion in an in vivo porcine model. A total of 72 colleagues from 50
      different centers of 12 countries participated, including orthopedic, trauma,
      visceral, neuro-, and vascular surgeons. Quality and effectiveness of the course
      were evaluated by a questionnaire after a 1.5- to 2.5-year period. RESULTS:
      During this time, 42.2% of the participating centers had applied the new
      technique successfully in man. Centers which participated in the course with a
      team that included a skilled laparoscopic surgeon and an orthopedic or trauma
      surgeon introduced the technique more frequently to clinical practice (57.9%)
      than those represented by only one participant (30. 8%). Moreover, there was a
      tendency toward a more frequent introduction of the technique to clinical
      practice in centers associated with university hospitals (57.1% vs. 29.2%),
      indicating the requirement of a particular infrastructure for this complex
      interdisciplinary procedure. Almost all participants (98.3%) agreed that for
      novel surgical techniques requiring advanced technical skills, there should first
      be training in a large animal model before the technique is applied in man.
      CONCLUSIONS: Complex laparoscopic procedures (i.e., laparoscopic spine surgery)
      can be successfully learned by in vivo hands-on training courses. We propose that
      for refinements and modifications of the technique (e.g. , the lumboscopic
      approach), there should also first be training in a large animal model before
      these are applied in man.

PMID- 9918611
TI  - Video-assisted thoracoscopic surgery to the upper thoracic spine.
AB  - BACKGROUND: The standard open technique for exposure of the upper thoracic spine,
      T1-T4, usually requires a difficult thoracotomy. From November 1, 1995 to June
      30, 1997, eight patients underwent video-assisted thoracoscopic spinal surgery in
      our institute to treat their upper thoracic spinal lesions endoscopically.
      METHODS: A new approach, the so-called "extended manipulating channel method,"
      was used in this series that allows the combined use of video-assisted
      thoracoscopy and conventional spinal instruments to enter the chest cavity freely
      for the procedures. Patients' ages ranged from 44 to 89 years (average, 60
      years). Definitive diagnoses included two pyogenic spondylitis and six spinal
      metastases. Five patients presented initially with myelopathy. RESULTS: There
      were no deaths or neurologic injuries associated with this technique. The mean
      surgical time was 3.1 h. The mean duration of chest tube retention was 3.3 days.
      The mean total blood loss was 1,038 ml, and two patients had a blood loss of more
      than 2,000 ml owing to bleeding from epidural veins or raw osseous surfaces.
      Complications included one superficial wound infection and one subcutaneous
      emphysema that resolved spontaneously. In this series, there was no need of
      conversion to open thoracotomy for the patients. CONCLUSIONS: The thoracoscopy
      assisted spinal technique using the extended manipulating channels, usually 2.5
      3.5 cm, allows variable instrument angulations for manipulation. The mean
      surgical time (3.1 h) was considered no longer than for an open technique for the
      equivalent anterior procedure. Such an approach can achieve less procedure
      related trauma and has proved to be a good alternative to other treatment
      modalities.

PMID- 9918612
TI  - Perceptual-motor coordination in an endoscopic surgery simulation.
AB  - BACKGROUND: This study examined perceptual-motor coordination with an apparatus
      that simulated a situation representative of endoscopic surgery. METHODS:
      Participants were trained with one arrangement of the apparatus, then tested with
      an alternative arrangement in which either the positions of the camera, the
      surgeon, or the objects in the surgical field were altered. RESULTS: Results
      showed that changes of either the camera's position or the surgeon's position
      disrupted performance. However, when the camera and surgeon positions were
      changed together, skilled performance was maintained. CONCLUSIONS: This suggests
      that skill depends on a consistent mapping between the virtual hands and eyes,
      but not on the particular visual or motor orientations. The results suggest that
      movements of the camera during surgery can disrupt coordinated action. Also, in
      the design of training simulators, the mapping between camera and instruments may
      be more important than the static appearance of the displays or the topology of
      the movements.

PMID- 9918613
TI  - Diagnostic laparoscopy through the right lower abdominal incision following open
      appendectomy.
AB  - BACKGROUND: Diagnostic laparoscopy through the right lower abdominal incision
      following open appendectomy for suspected acute appendicitis may help in making
      the correct diagnosis in the absence of pathology of the appendix. METHODS:
      Fourteen patients with a clinical diagnosis of acute appendicitis underwent
      diagnostic laparoscopy through the right lower quadrant incision after open
      appendectomy to exclude further pathology in the case of a noninflamed appendix.
      RESULTS: In 10 of the 14 patients, laparoscopy helped to correct the diagnosis.
      In two patients, the etiology of the acute right lower abdominal pain remained
      unclear. In two others, histological examination showed acute appendicitis
      despite a normal macroscopic appearance. CONCLUSIONS: Diagnostic laparoscopy
      through the right lower quadrant incision may help to correct the diagnosis in
      patients who are operated on for clinically acute appendicitis but in whom no
      acute appendicitis or other pathological findings are seen.

PMID- 9918614
TI  - Intraperitoneal thermal variations during laparoscopic surgery.
AB  - BACKGROUND: The aim of this study was to measure thermal variations during
      laparoscopy in the vicinity of heat sources such as monopolar (MC) and bipolar
      coagulation (BC) and to evaluate their possible negative consequences for the
      patient. METHODS: This study included 43 patients who underwent laparoscopic
      cholecystectomy. The temperature measurements were taken with a sterile thermal
      probe (Mallinkrot Medical) introduced through a 5-mm trocar coupled with a
      recording monitor reading variations between 20 and 80 degreesC. The variation in
      temperature was measured as a function of the power applied to the electrodes (20
      or 30 W) and in relation to the distance (1, 2, 3, 4, and 5 cm) from the
      electrodes. RESULTS: The temperature varied by 3 degrees for BC and 29 degrees
      for MC when the distance increased from 1 to 5 cm. With respect to the power
      delivered, 20 or 30 W, the variations were 1 degrees for BC and 17 degrees for
      MC. CONCLUSIONS: The minimal temperature variations associated with the use of BC
      makes it the option of choice for operating near structures such as the common
      bile duct or the gastrointestinal tract.

PMID- 9918615
TI  - Laparoscopic rectopexy according to Wells.
AB  - BACKGROUND: The laparoscopic approach usually reduces the morbidity of procedures
      performed by laparotomy. The aim of this study was to demonstrate the usefulness
      of laparoscopic rectopexy. METHODS: A total of 37 patients were included in this
      prospective study. The indication was true rectal prolapse in all patients.
      Incontinence was seen in 33% of the patients. A slightly modified Wells procedure
      was performed laparoscopically. Postoperatively, the patients were evaluated for
      resolution of the prolapse and incontinence. They were also questioned about
      their satisfaction with the procedure. RESULTS: Laparoscopy was successful in all
      but one case. Follow-up is available in 32 of 37 patients. Prolapse was cured in
      all patients, and the incontinence resolved in 11 of 12. In addition, 38% of the
      patients experienced significant constipation preoperatively versus 5%
      postoperatively.

PMID- 9918616
TI  - The "floppy" Nissen fundoplication is a completely competent antireflux valve.
AB  - BACKGROUND: The antireflux capacity of various gastric fundoplications combines
      the creation of a valve (flapper or nipple) with recreation of a sharp
      cardioesophageal angle. Experimental comparison of valve competency and
      appropriate valve geometry is incomplete despite wide application of these
      techniques. Our primary aim was to compare the competency of several antireflux
      valves in explanted cadaver stomachs. Our secondary aim was to understand better
      the geometry of the gastric fundus in empty and full stomachs. METHODS: Stomachs
      with 6-8 cm of distal esophagus were harvested from 18 fresh cadavers. With the
      stomach empty, the greater and lesser curvature length and the transverse
      dimensions of the anterior and posterior surface of the stomach in the fundus,
      body, and antrum were measured. The pylorus was tied off over a catheter; the
      stomachs were inflated with water; and reflux occurred. Intragastric pressure was
      measured during inflation with a needle inserted in the side of the stomach. A
      clamp was then placed on the esophagus, and the stomach was inflated to a
      pressure of 10 mmHg. Gastric measurements were recalculated in the distended
      stomach. The stomachs were deflated, the clamp removed, and a 2-cm Nissen
      fundoplication as well as 270 degrees and 180 degrees posterior fundoplications
      were performed over a 60 Fr dilator. The stomachs were reinflated while the
      pressure was transduced. The inflation was stopped when reflux occurred or when
      the fundoplication disrupted. RESULTS: The stomachs expanded symmetrically when
      filled with water except for the fundus in which the anterior gastric wall
      lengthened by more than 100% and the posterior gastric wall lengthened by about
      50%. In the untreated stomachs, reflux occurred at a pressure of 3.0 +/- 1.0
      mmHg. After fundoplication, reflux never occurred, but the sutures pulled out of
      the stomach or esophagus at 28.6 +/- 16.8 mmHg. Posterior fundoplications
      refluxed water in several stomachs. CONCLUSIONS: When filled, the anterior fundus
      expands to a greater degree than the posterior fundus, offering more tissue for
      creation of floppy fundoplication. The "floppy" Nissen fundoplication is
      completely competent, suffering a degradation before allowing reflux. The
      posterior partial fundoplication is unpredictable in its competency.

PMID- 9918617
TI  - Cost effectiveness of routine type and screen testing before laparoscopic
      cholecystectomy.
AB  - BACKGROUND: The aim of this study was to assess the cost effectiveness of routine
      preoperative blood type and screen testing before laparoscopic cholecystectomy.
      METHODS: All 2,589 laparoscopic cholecystectomies and 603 open cholecystectomies
      performed at our institution between January 1990 and December 1996 were
      retrospectively reviewed to identify the incidence and causes of blood
      transfusions. With the use of ICD-9-CM coding, a computerized retrospective
      research was done to match the corresponding codes for the aforementioned
      operations and blood transfusion. Individual charts were reviewed to identify the
      indications for blood transfusion. RESULTS: Of the 2,589 laparoscopic
      cholecystectomies performed, 12 patients required blood transfusion, and of the
      603 open cholecystectomies, 33 patients required blood transfusion. The incidence
      of blood transfusions was 0.46% for laparoscopic cholecystectomy and 5.47% for
      open cholecystectomy. Two of the blood transfusions given intraoperatively were
      due to major vascular injury in the laparoscopic cholecystectomy group. The
      remaining blood transfusions were found to be the result of preexisting medical
      conditions including sickle-cell anemia, end-stage renal disease, and chronic
      iron deficiency anemia. CONCLUSIONS: Laparoscopic cholecystectomy has become a
      widely used therapeutic modality in general surgery. The procedure is safe,
      effective, and well tolerated by the patient. In the era of managed healthcare,
      the cost effectiveness of commonly ordered tests is frequently questioned. In the
      absence of preoperative indications, routine preoperative blood type and screen
      testing should be eliminated for laparoscopic cholecystectomy. The elimination of
      routine preoperative blood type and screen testing could have saved our
      institution $79,800 during a 6-year period.

PMID- 9918618
TI  - Abdominal, laparoscopic, and vaginal hysterectomy with bilateral salpingo
      oophorectomy: a feasibility study for further evaluation in randomized trials.
AB  - BACKGROUND: The abdominal route is the traditional method of performing
      hysterectomy with bilateral salpingo-oophorectomy. In a feasibility study, we
      compared a nonconventional (vaginal) route for bilateral salpingo-oophorectomy at
      the time of vaginal hysterectomy (VH + BSO) to similar forms of hysterectomy
      performed abdominally or with operative laparoscopy. METHODS: Fifty-nine patients
      were subject to either total abdominal hysterectomy and bilateral salpingo
      oophorectomy (TAH + BSO; n = 19), or laparoscopic-assisted vaginal hysterectomy
      and bilateral salpingo-oophorectomy (LAVH + BSO; n = 19) or VH + BSO (n = 21).
      RESULTS: VH + BSO resulted in a shorter operating time compared to LAVH + BSO (p
      < 0.001), shorter hospital stay compared with TAH + BSO (p = 0.001), and quicker
      long-term recovery compared to the other two operations. CONCLUSION: This
      preliminary but significant study shows that the vaginal route for salpingo
      oophorectomy at the time of vaginal hysterectomy is superior to other methods of
      hysterectomy. A randomized trial is needed to confirm these initial findings.

PMID- 9918619
TI  - The role of conversion in laparoscopic colorectal surgery: Do predictive factors
      exist?
AB  - BACKGROUND: This study was performed to analyze the reasons for conversion of
      laparoscopic colorectal procedures to open surgery and to identify risk factors.
      METHODS: All patients who underwent laparoscopic colorectal surgery at our
      institution were enrolled in a prospective trial. The causes of conversion were
      analyzed. Statistical analysis, including a logistic regression model, was
      performed to identify factors that would predict an increased risk of conversion.
      RESULTS: A total of 300 laparoscopic or laparoscopic-assisted procedures for both
      benign and malignant diseases were performed within 5 years. Mean patient age was
      61.4 years (range, 17-93). There were 218 women and 82 men. Major complications
      occurred in 8.6%, and 30-day-mortality rate was 1.1%. Postoperative
      hospitalization was 13.9 days (range, 6-47). Conversion occurred in 22 cases
      (7.3%). The mean age of the converted group was 64.7 years (range, 31-93).
      Postoperative hospital stay was 15.0 days (range, 10-25). The main reasons for
      conversion to open surgery were inflammation, obesity, anesthetic problems,
      technical difficulties, intraoperative complications, and intraoperative
      decisions concerning oncological resection. The conversion rate was 14.6% in
      patients who underwent sigmoid resection for diverticular disease. By univariate
      analysis, statistically significant factors defining a higher risk of conversion
      were male gender (p = 0.0029), age from 55 to 64 years (p = 0.0015), extreme body
      status (p = 0.0001), and diagnosis of diverticular disease (p = 0.0011).
      According to the logistic regression model, all four factors combined would give
      a probability of conversion of 70.3%. CONCLUSIONS: The risk factors contributing
      to the possibility of conversion included male gender, age between 55 and 64
      years, extreme body status, and diverticular disease. Using these data, patients
      with an increased likelihood of conversion can be identified. However, if
      conversion is necessary, laparoscopic colorectal surgery can be safely applied to
      the patients with no additional morbidity.

PMID- 9918620
TI  - Hand-assisted laparoscopic digestive surgery provides safety and tactile
      sensation for malignancy or obesity.
AB  - BACKGROUND: Some of the persistent problems associated with laparoscopic surgery
      stem from the inability of the surgeon to palpate the abdominal contents during
      the operation. This lack of tactile sensation can lead to poor abdominal
      exploration, difficulty in extracting the organs, and a relatively long operation
      time compared to conventional procedures. The Dexterity Pneumo Sleeve is a new
      device that allows the surgeon to insert his or her hand into the abdominal
      cavity through a small incision while preserving the pneumoperitoneum. METHODS:
      Recently, 13 of our patients underwent hand-assisted advanced laparoscopic
      surgery using this device. In this series, we had two cases of gastrectomy, two
      cases of gastric bypass for morbid obesity, two Whipple cases for periampullary
      tumor, and seven cases of bowel resection. On the basis of this series, we were
      able to assess the utility of this device. RESULTS: Satisfactory pneumoperitoneum
      was maintained in 12 of 13 cases. The length of the skin incision was 7.8 cm on
      average, which was almost the same size as surgeon's glove. The device proved to
      be very useful for tissue retraction and abdominal exploration in all cases and
      for intracorporeal knot tying in some cases. CONCLUSIONS: We found that the
      device permitted an easier dissection, resection, and anastomosis. It also helped
      to decrease the operation time.

PMID- 9918621
TI  - Laparoscopic transabdominal lumboperitoneal shunt.
AB  - Communicating hydrocephalus can be handled either by the ventriculoperitoneal or,
      occasionally, the ventriculoatrial shunt. The lumboperitoneal shunt is another
      option. It does not require a transcranial approach; therefore, it is safer for
      the patient. We describe a technique that can be performed easily by a skilled
      laparoscopic surgeon through an anterior approach transabdominally. The
      lumboperitoneal (LP) shunt is placed laparoscopically under direct videoscopic
      vision, with the catheter inserted transabdominally through the L3 disc space
      into the thecal sac. In our patient, the lumboperitoneal shunt was placed at the
      L3 disc space for communicating hydrocephalus. There were no intraoperative or
      postoperative complications. The LP shunt can be easily placed by a skilled
      laparoscopic surgeon. The incidence of infection and complications is lower, and
      the patency rate is higher. This should be the initial choice for communicating
      hydrocephalus.

PMID- 9918622
TI  - Abdominal laparoscopic approach for thoracic epiphrenic diverticulum.
AB  - The true incidence of epiphrenic esophageal diverticulum is unknown.
      Traditionally, diverticulectomy via a left thoracic approach has represented the
      gold standard. Trans-hiatal esophageal dissection under laparoscopy is feasible,
      but has not, to our knowledge, been applied before in the treatment of epiphrenic
      esophageal diverticulum.

PMID- 9918623
TI  - Video-assisted thoracoscopic repair of an intercostal pulmonary hernia.
AB  - Pulmonary hernias are extremely rare. They are usually treated with open surgical
      procedures. We describe a case in which a large, spontaneously acquired
      intercostal pulmonary hernia was successfully repaired by video-assisted
      thoracoscopic surgery (VATS).

PMID- 9918624
TI  - Bile leakage resulting from clip displacement of the cystic duct stump: a
      potential pitfall of laparoscopic cholecystectomy.
AB  - We present the case of a patient who underwent successful endoscopic nasobiliary
      drainage (ENBD) for bile leakage resulting from clip displacement of the cystic
      duct stump sustained during a laparoscopic cholecystectomy (LC). This 69-year-old
      man was admitted with symptomatic cholecystolithiasis. After LC was performed,
      intraoperative cholangiography (IOC) revealed no abnormal findings. However,
      postoperatively, bilious material began to appear from the intraabdominal drain.
      Subsequent endoscopic retrograde cholangiopancreatography (ERCP) showed bile
      leakage from the end of the cystic duct stump. ENBD was performed.
      Cholangiography using the ENBD tube 14 days later failed to show a bile leak. The
      ENBD was subsequently removed. The patient improved rapidly with no complaints.
      Bile leakage due to clip displacement from the cystic duct stump is a potential
      pitfall of LC, especially if IOC is normal. We recommend careful cystic duct
      ligation, combined with the use of superior quality ligation clips, to prevent
      this complication. ENBD is a useful technique to prevent bile leakage after this
      complication.

PMID- 9918625
TI  - Laparoscopic resection of a pancreatic mucinous cystadenoma using laparosonic
      coagulating shears.
AB  - A 71-year-old woman with a solitary mucinous cystic neoplasm of the pancreatic
      tail complained of back pain. A laproscopic distal pancreatectomy was performed.
      Laparosonic coagulating shears (LCS) were employed for dissection of the
      surrounding tissue and transection of the pancreas. The main pancreatic duct was
      clipped. There was no evidence of bleeding or pancreatic leakage from the
      transection surface. Pathologic examination showed the tumor to be a mucinous
      cystadenoma. The postoperative course was uneventful. The LCS was effective in
      this application.

PMID- 9918626
TI  - Instruments for minimally invasive surgery: principles of ergonomic handles.
AB  - Although the advantages of minimally invasive surgery (MIS) have been clearly
      established for the patient, the surgeon must cope with disadvantages caused by
      unergonomic instrument handles. Pressure areas and persisting nerve lesions have
      been described in the literature. The shape of the instrument handles has been
      identified as the reason for these disorders. To prevent these, it is necessary
      to use ergonomically designed handles for MIS instruments. Anatomic, physiologic,
      and ergonomic facts as well as the results of the authors' own experiences and
      tests are presented. On this basis, an ideal ergonomic working posture for the
      laparoscopic surgeon and an optimal grasp for manipulating the instruments'
      functional elements are recommended. To enable the surgeon to evaluate ergonomic
      handles for MIS instruments according to his own needs, 14 criteria for genuine
      "ergonomic handles" are established. On the basis of these criteria, deficiencies
      of handles currently available (ring and shank handles at an angle or with axial
      extension to the instrument shaft, and pistol handles) are discussed.
      Furthermore, new handles, developed by the authors according to the criteria for
      genuine ergonomic handles, are presented.

PMID- 9918627
TI  - Laparoscopic intracorporeal ultrasound cystic duct length measurement: a new
      technique to prevent common bile duct injuries.
AB  - The incidence of common bile duct injury remains high. Intracorporeal ultrasound
      mapping of cystic duct anatomy, prior to laparoscopic cholecystectomy (LC), may
      assist surgeons in avoiding common bile duct injuries. A technique for
      intraoperative intracorporeal predissection ultrasound imaging (IIPUI) of the
      cystic duct length was tested. During LC, gallbladder adhesions were lysed, and
      with the gallbladder retracted by grasping forceps, the ultrasound examination
      was performed. Using a 7.5-MHz articulating ultrasound probe, visualization of
      the extrahepatic biliary tree was obtained in five separate planes. Success in
      visualizing each plane, time for ultrasound examination, and predissection
      accuracy of cystic duct length measurement were recorded. Intraoperative
      cholangiography or direct measurement of the dissected cystic duct was used to
      determine accuracy of the ultrasound cystic duct length estimates. Forty-three
      patients underwent IIPUI during LC. The time required to perform the examination
      varied, with a range of 5 to 17 min (mean 9.5 min). Success of visualization in
      planes 1 through 5 was 44%, 95%, 98%, 98%, and 70%, respectively. The accuracy
      rate for cystic duct length ultrasound measurement was 87.1%. No complications
      related to the examination were observed. In this preliminary study, cystic duct
      length was determined by predissection intracorporeal ultrasound with a high
      level of accuracy. Predissection imaging may assist in preventing common bile
      duct injury during LC.

PMID- 9918629
TI  - Semiautomatic suturing device (Maniceps) for laparoscopic surgery.
AB  - The only automatic device now available to laparoscopic surgeons is Endo-Stitch,
      which is costly for single use and has the disadvantage of leaving a large needle
      hole in the tissue. A semiautomatic suturing device (Maniceps) for laparoscopic
      use was developed from a forceps-type of needle holder for open pelvic surgery.
      The first generation of the instrument was designed for use with the abdominal
      wall-lift method of laparoscopic surgery, whereas the second generation can be
      applied for gas insufflation as well. Exchange of the needle is done by an
      automatic grasping action of a resilient slit in one jaw and by manual pull-down
      of the needle via the thread onto the other jaw. The new instrument was employed
      in 10 cases of laparoscopic surgery for various procedures including suture of
      the perforated gallbladder wall and running suture of the peritoneum after mesh
      placement in transabdominal repair of inguinal hernia. Maniceps provides an
      economic advantage and has the merit of a smaller needle hole.

PMID- 9918628
TI  - Videolaparoscopic implantation of long-term peritoneal dialysis catheters.
AB  - Implantation of peritoneal dialysis catheters by traditional laparotomy or
      trocar/guidewire techniques leaves the operator blind to the actual location and
      configuration of the peritoneal catheter tubing; it is associated with drainage
      dysfunction from catheter obstruction in 10-22% of catheter placements. This
      report presents a laparoscopic technique that allows accurate tube placement with
      complete visualization of the implant procedure. The peritoneal dialysis catheter
      was implanted through a port inserted in a paramedian location. Videoscopic
      monitoring was performed through a second port inserted in a pararectus location
      on the opposite side of the abdomen. Nitrous oxide gas was utilized for
      peritoneal insufflation thus permitting the procedure to be accomplished under
      local anesthesia. Follow-up of </=12.7 months (median, 4.4) for the first 28
      patients revealed a high rate of successful catheter function with an outflow
      obstruction rate of 3.6%. The procedure was well tolerated by patients under
      local anesthesia on an outpatient basis. Videolaparoscopy is ideally suited for
      peritoneal dialysis catheter implantation. Visual conformation of proper catheter
      location and configuration during the implant process are associated with lower
      incidences of outflow failure.

PMID- 9918630
TI  - Needle and trocar injury during laparoscopic surgery in Japan.

PMID- 9918631
TI  - The author replies 

PMID- 9918632
TI  - Inadequate detection of accessory spleens and splenosis with laparoscopic
      splenectomy: a shortcoming of the laparoscopic approach inhematological diseases.

PMID- 9918634
TI  - Global statement on deep venous thrombosis prophylaxis during laparoscopic
      surgery.SAGES position statement. Society of American Gastrointestinal Endoscopic
      Surgeons.

PMID- 9918633
TI  - The author replies 

PMID- 9918635
TI  - Global statement on new procedures.SAGES position statement. Society of American
      Gastrointestinal Endoscopic Surgeons.

PMID- 9918637
TI  - News and notices 

PMID- 9918636
TI  - Guidelines for diagnostic laparoscopy.SAGES guidelines. Society of American
      Gastrointestinal Endoscopic Surgeons.

PMID- 9918638
TI  - MRI for the diagnosis and follow-up of myocarditis.

PMID- 9918639
TI  - Homocysteine, B vitamins, and atherosclerosis.

PMID- 9918640
TI  - A morphometric analysis of the posed smile.
AB  - A fundamental goal of orthodontics is to improve the smile, but no objective
      criteria exist to assess the lip-teeth relationship, establish objectives of
      treatment or measure treatment outcome. Here we propose a method to digitally
      measure the smile characteristics of orthodontic patients. Specifically, the
      'posed smile' is measured. By definition the posed smile is voluntary and not
      elicited by an emotion. It can be a learned greeting or a signal of appeasement
      and can be sustained. The posed smile is reliably repeatable. The multimedia
      computer program for smile measurement we developed was based on studies of the
      utility of the smile photograph and the assessment of the lip-teeth
      characteristics of the posed smile in treated and untreated patients. On the
      computer screen a grid, or smile mesh, employs horizontal and vertical lines to
      measure eleven attributes of a smile. Not all orthodontically 'well-treated'
      patients with exemplary plaster casts exhibit desirable anterior tooth display
      while smiling. We suggest that the photographic analysis of an unstrained posed
      smile might be a standard orthodontic record.

PMID- 9918641
TI  - Efficiency of multi-strand steel, superelastic Ni-Ti and ion-implanted Ni-Ti
      archwires for initial alignment.
AB  - In a clinical trial involving 155 dental arches with irregularity > 5 mm, the
      rate of alignment was used to compare the alignment efficiency of 16 mil
      superelastic Ni-Ti versus 17.5 mil triple-stranded steel archwires, and to
      determine whether ion implantation of the Ni-Ti wire improved its performance.
      Subjects were randomly assigned to archwire types; both 18 and 22 slot edgewise
      appliances were employed. Pre-treatment equivalence of the experimental groups
      was verified. Anterior irregularity was determined monthly (using Little's
      irregularity index) until it decreased below 2 mm, and the elastomeric ligatures
      were replaced at each appointment. Effective tooth movement occurred with each of
      the archwire types. There were no significant differences among wires, but the
      rate of alignment was significantly faster in the lower arch for subjects with
      the 22 slot appliance.

PMID- 9918642
TI  - Attitudes and compliance of pre-adolescent children during early treatment of
      Class II malocclusion.
AB  - A survey was administered to 168 parents and their children at the end of mixed
      dentition treatment for Class II correction utilizing bionators and headgears to
      investigate attitudes of parents and patients toward bionators and headgears and
      to elicit factors associated with compliance. Directional differences between
      parent and child responses occurred frequently with agreement ranging from 41 to
      100%, averaging 69% overall. The results indicate that the orthodontic patient
      population has medical and dental health as a priority. While parental and child
      reasons for seeking treatment may be different, it appears that both groups seek
      care for perceived benefits of health, decreased present and future oral
      problems, peer influences, and dental self image improvement. Additionally,
      children who are undergoing treatment perceive that others do not understand what
      they are going through, they may be embarrassed, and some may break their
      appliances to annoy the parent or orthodontist. Pain, decreased ability to speak,
      and difficulty chewing were reported to decrease appliance wear. Patient
      understanding of the treatment goals was reported to increase compliance. The
      bionator caused more instances of speech problems and associated non-compliance
      than the headgear. The headgear caused more instances of pain, but did not cause
      significantly less associated compliance than the bionator. The results suggest
      that bolstering the patient-orthodontist relationship, informing the patient
      about the treatment goals, methods, and their individual role, and offering
      immediate short term rewards can potentially increase patient compliance.

PMID- 9918644
TI  - Prediction of mandibular third molar impaction in the orthodontic patient from a
      panoramic radiograph.
AB  - In this study we explored the predictability of mandibular third molar
      impactions. Serial panoramic radiographs from 50 non-extraction and 15 extraction
      patients were traced for various angular and linear measurements. A linear
      discriminant function analysis was performed for each stage of third molar
      development. The results indicate that the earliest stages of development have
      very little predictive value. Accordingly, a justification for the oft-practiced
      enucleation procedure cannot be made. Although the more the tooth is developed,
      the higher is the accuracy of prediction, two earlier stages where the crown is
      fully formed or the roots 1/3 formed possess high predictive values. Based on our
      data, impaction of third molars in the mandible is a predictable event both in
      extraction and non-extraction patients.

PMID- 9918643
TI  - Clinical comparison between a resin-reinforced self-cured glass ionomer cement
      and a composite resin for direct bonding of orthodontic brackets Part 1: Wetting
      with water.
AB  - The purpose of this study was to compare the clinical performance of a resin
      reinforced self-cured glass ionomer cement to a standard composite resin in a
      split mouth design, by using both systems for direct bonding of orthodontic
      stainless steel brackets in every patient. Forty eight patients (34 females and
      14 males, of which 29 were adults > 18 years of age) with fixed appliances were
      followed for a mean period of 10 months (range 4-16 months). The performance of
      864 stainless steel brackets was evaluated: 404 brackets were bonded with GC Fuji
      Ortho glass ionomer cement (GC Industrial, Tokyo, Japan) onto teeth soaked with
      water, and 460 were bonded with System 1+ composite resin (Ormco, Glendora, CA).
      System 1+ recorded an overall failure rate (18.2%) significantly higher (p <
      0.05) than GC Fuji Ortho (7.9%). There were no statistically significant
      differences (p > 0.05) between the failure rates in the upper and lower arches
      with either material. Both in the upper and lower arches, System 1+ exhibited a
      failure rate significantly higher (p < 0.05) than GC Fuji Ortho. When the bonding
      performance of the six anterior teeth was compared with first and second
      premolars, no statistically significant differences were found (p > 0.05) between
      bonding agents in either arch. System 1+ exhibited a failure rate significantly
      higher (p < 0.05) than GC Fuji Ortho, both in the anterior and posterior
      segments. Both bonding agents failed mainly at the enamel-adhesive interface,
      without causing any damage to the enamel.

PMID- 9918645
TI  - Mandibular stability after sagittal split ramus osteotomy without post-operative
      maxillomandibular fixation in the treatment of prognathic patients with symmetric
      mandibles.
AB  - This study was designed to examine post-operative stability in prognathic
      patients with symmetric lower jaws who underwent sagittal split ramus osteotomy
      (SSRO) of the mandible without post-operative maxillomandibular fixation (MMF).
      Twenty prognathic patients with symmetric mandibles were investigated. An
      appliance for repositioning the proximal segment and titanium screw fixation was
      applied in all patients. Ten patients underwent post-operative MMF with stainless
      steel wire (mean duration, 9.6 days) and intermaxillary rubber traction after
      removal of the MMF (Group I), and the remaining ten underwent intermaxillary
      rubber traction only (Group II) post-operatively. Cephalograms were obtained 2-3
      days post-operatively, and 3, 6, and 12 months after surgery. Changes in the
      positions of upper incisors (U-1), lower incisors (L-1), B-point, and pogonion
      were examined on lateral cephalograms. In the early stages of follow-up,
      decreases in the overbite tended to be more marked in Group I than in Group II,
      and the forward movement of each standard point was significantly larger in Group
      I than in Group II. No significant differences, however, were revealed between
      the two groups at 12 months after surgery. Forward movement of anterior
      cephalometric landmarks, post-operatively, in Group II were significant, however,
      this pattern differed from Group I, in which big changes occurred in the early
      stages after surgery. Although the patterns of post-operative changes in the two
      groups are different, there are no significant differences in their post
      operative stability in long-term follow-up. Therefore, post-operative MMF may be
      avoided when prognathic patients with symmetric mandibles undergo SSRO with an
      appliance for repositioning the proximal segment and titanium screw fixation.

PMID- 9918646
TI  - The rationale, evolution and clinical application of the self-ligating bracket.
AB  - There is ample evidence in the literature that conventional orthodontic mechanics
      while intended to move teeth efficiently rarely achieve atraumatic remodeling of
      periodontal tissues. The vascular supply is often interrupted, which in turn
      affects the oxidative metabolism. Moreover, teeth splinted in groups do not
      appear to move as efficiently as single teeth. The novel bracket design and
      treatment regimen described in this report allow teeth to move individually, yet
      stay within a group. The self-ligating bracket design allows for rapid leveling
      because teeth drift along the path of least resistance with little or no friction
      between the bracket and slot of the wire. The hinge mechanism eliminates much of
      the friction created by the conventional wire or latex ties used to secure the
      archwire in the bracket slot. Thus, sliding mechanics is achieved in the true
      sense of the word. This system is capable of increasing the appointment
      intervals, and possibly reducing the overall treatment time.

PMID- 9918647
TI  - Loose joint bodies of the temporomandibular joint: a case report.
AB  - Osteochondral loose bodies are an uncommon finding in the temporomandibular joint
      (TMJ), but occur relatively frequently in large joints such as the knee, elbow,
      hip, wrist, and ankle. Loose joint bodies can be divided in three groups: 1)
      synovial chondromatosis; 2) osteochondral fracture fragments and; 3) cases of
      degenerative arthritis or avascular necrosis. The most common clinical features
      of loose joint bodies are pain, swelling, joint noise and impaired joint
      movements. A case of loose joint bodies of the temporomandibular joint is
      presented. The pantomograph and lateral cephalograph revealed several irregularly
      shaped, variably sized radiopaque structures in the region of the right
      temporomandibular joint. CT and MR scans confirmed the initial diagnosis. The
      dimensions of the loose joint bodies varied from 1-2 to 5-6 mm. In this patient,
      the loose joint bodies may have been secondary to osteoarthritis, may have
      preceded and caused the degenerative changes, or may be only a coincidental
      finding.

PMID- 9918648
TI  - Composite hooks enhance rotational control.
AB  - We find hooks placed in positions of convenience useful in correcting rotations,
      especially with lingual appliances. The steps involved in building them are
      straightforward. Following acid etching of the spot where the hook is to be
      placed, a small amount of bonding material is carried onto the enamel surface and
      a base established by a series of circular motions with the tip of an explorer.
      The bonding material is then extruded with the tip of the explorer. As soon as
      the material is extruded to the desired length and curvature, the UV light is
      applied. Of course, if needed, bigger hooks can be constructed and then trimmed
      to shape with a bur. A short-beak band remover works best (in a scraping motion)
      for the removal of these hooks. The following figures illustrate the point (Figs.
      1-7).

PMID- 9918649
TI  - Measuring protein synthesis by mass isotopomer distribution analysis (MIDA).
AB  - The measurement of protein kinetics by isotopic techniques has been hindered by
      the long-standing difficulty of accurately measuring the isotope content of the
      biosynthetic precursor pool (aminoacyl-tRNA in tissues). Mass isotopomer
      distribution analysis (MIDA) is a stable isotope-mass spectrometric (MS)
      technique for measuring biosynthetic precursor enrichments from measurements on a
      polymeric product, based on combinatorial probabilities of labeled and unlabeled
      monomeric subunits. Proteins contain complex isotopomer patterns as a result of
      their relatively high molecular mass, however, so that resolution of the
      individual mass isotopomers in the polymeric product (an analytic requirement for
      MIDA) is technically difficult. An approach for measuring protein synthesis by
      MIDA is described and tested here: First, in vitro, using a synthetic peptide
      present in human serum albumin; and then, in vivo, for albumin synthetic rate in
      rats. A peptide contained in human serum albumin (SVVLLLR) and theoretically
      recoverable from trypsin/chymotrypsin proteolysis was synthesized by solid-phase
      peptide synthesis using known mixtures of natural abundance and [5,5, 5
      2H3]leucine. Additionally, enriched and natural abundance peptides were mixed in
      vitro to simulate in vivo biosynthesis and to address problems of instrument
      accuracy, precision, and data management. The mass isotopomer patterns of the
      synthetic peptides were analyzed using electrospray ionization (ESI) with both
      magnetic sector and quadrupole mass analyzers. The resolution of the magnetic
      sector was superior to that of the quadrupole instrument, but accuracy and
      precision in the measurement of mass isotopomer abundances and kinetic parameters
      were comparable and both gave values close to those predicted. Next, rats were
      infused with [5,5,5-2H3]leucine intravenously, and a leucine-rich peptide was
      isolated and purified from trypsin-digested rat serum albumin (RHPDYSVSLLLR, 1456
      Da) and then analyzed by ESI-MS using a magnetic sector instrument. Precursor
      pool enrichments and fractional synthetic rates (0.45 +/- 0.03 day-1, t1/2 = 1.53
      +/- 0.09 days) were calculated. Biosynthetic rates of rat serum albumin were
      congruent with previously published values. In summary, measurement of protein
      synthesis and precursor pool enrichments by MIDA is technically feasible and
      practical in vivo using proteolytically derived peptides and ESI-MS analysis.

PMID- 9918650
TI  - General numerical treatment of competitive binding kinetics: application to
      thrombin-dehydrothrombin-hirudin.
AB  - This paper describes a general numerical method for the determination of rate
      constants that characterize the binding of a ligand L simultaneously and
      competitively to two different receptor molecules, R1 and R2. The experimental
      data consist of changes in the concentration of one receptor (e.g., R1) monitored
      over time. An example problem is represented by hirudin (L) binding to thrombin
      (R1) and to a chemical mutant of thrombin (R2). The published experimental data
      [Wedemeyer et al. (1997) Anal. Biochem. 248, 130-140], previously analyzed by
      using an appropriate algebraic method, were reanalyzed here by numerical
      integration [Kuzmic (1996) Anal. Biochem. 237, 260-273]. This general numerical
      method offers the following advantages. (1) It provides an estimate for the lower
      limit on feasible values of association rate constants. (2) It is many orders of
      magnitude more accurate. (3) It is easily extensible to more complicated reaction
      mechanisms. (4) It uses a simpler formalism and it is thus more accessible to
      nonmathematicians. (5) A suitable computer program for the analysis of
      competitive binding kinetics can be obtained via the Internet
      (http://www.biokin.com).

PMID- 9918651
TI  - Quantification of ribonucleotide reductase expression in wild-type and
      hydroxyurea-resistant cell lines employing in situ reverse transcriptase
      polymerase chain reaction and a computerized image analysis system.
AB  - Ribonucleotide reductase (RR) is the enzyme responsible for converting nucleoside
      diphosphates to deoxynucleoside diphosphates, ensuring a balanced supply of
      deoxyribonucleotides for DNA synthesis. Expression of RR is tightly regulated,
      but it is affected by exogenous agents, such as hydroxyurea (HU), which
      inactivates the tyrosyl free radical on the small subunit of RR, R2. We have
      previously employed in situ reverse transcriptase (RT)-PCR to estimate expression
      of R2 in wild-type and HU-resistant human colon carcinoma cell lines and to
      correlate altered expression of R2 with changes in cell size and morphology. The
      current studies were undertaken to render this methodology more quantitative.
      Both wild-type and resistant cells were grown on partitioned glass slides and
      analyzed with in situ RT-PCR. Because both wild-type and resistant cells were
      analyzed under a single cover slip, protease digestion, reverse transcription,
      PCR, and color development were all performed under identical conditions. Images
      were analyzed with NIH Image 1.59 software. There was a highly significant
      correlation between expression of R2 and cell size for both sensitive and
      resistant cells (P = 0.0001, for both). When cell size was compared either with
      expression of R2 or cell shape, however, these correlated only in wild-type cells
      (P = 0.001 and 0.0001, respectively). These data demonstrate that normal cell
      growth in the unperturbed wild-type cell line was closely linked to expression of
      R2, whereas in the resistant variants which overexpress R2, these correlations
      were absent, suggesting that HU resistance is related to loss of linkage between
      R2 expression and cell growth and confirming previous data relating
      overexpression of R2 with multiple other changes in the cell growth repertoire.
      Thus, we have demonstrated for the first time a quantitative application of in
      situ RT-PCR.

PMID- 9918653
TI  - A microplate-based fluorometric assay for monitoring human cancer cell attachment
      to cortical bone.
AB  - A microplate-based fluorometric assay was developed for quantitation of cancer
      cell attachment to bone matrix. To evaluate this model system we used a panel of
      human cancer cell lines, including the human breast cancer cell line MDA-MB-231.
      For the assay, bovine cortical bone from the shaft of the femur was cut, turned,
      and sliced to 6-mm-diameter round 200-microm-thin disks and placed into the wells
      of a 96-well microplate. A fluorescent dye 2', 7'-bis(2-carboxyethyl-5(6)
      carboxyfluorescein (BCECF-AM) and a microplate fluorometer equipped with a
      standard filter set for fluorescein isothiocyanate were used to detect the cells
      attached to the bone disks. The fluorescence was enhanced during the measurement
      step by using a K+ solution (pH 8.0) containing the H+/K+ ionophore nigericin,
      which equilibrates internal and external pH. By taking advantage of the pH
      sensitivity of BCECF, the fluorescence intensity in the assay was increased 2.5
      times compared to cells loaded with calcein. The specificity of the assay was
      demonstrated with a specific immuneserum raised against the MDA-MB-231 cell line.
      The assay can be completed in 1 h and permits the use of a large number of
      samples and is therefore useful for screening potential drug candidates that
      could block cancer cell attachment to bone material. Moreover, the assay
      described can easily be used to characterize molecular structures involved in
      cell attachment to bone.

PMID- 9918652
TI  - Detection of cell and tissue surface antigens using up-converting phosphors: a
      new reporter technology.
AB  - A novel luminescent reporter for the sensitive detection of antigens in tissue
      sections or on cell membranes is described. It consists of submicron-size
      phosphor crystals (0.2-0.4 microm), which are surface labeled with avidin or
      antibodies and capable of binding specifically to antigens on intact cells or in
      tissue sections. These phosphor reporters exhibit two-photon, anti-Stokes
      luminescence by up-converting infrared to visible light and are named Up
      converting Phosphor Technology (UPT). They typically consist of
      yttriumoxysulfides doped with two different lanthanides exhibiting photostable,
      strong emission in the visible (blue, green, and red) upon excitation in the
      infrared. This report describes the conjugation of phosphor particles to
      NeutrAvidin with the subsequent use of this conjugate in a model system
      consisting of prostate-specific antigen in tissue sections and the CD4 membrane
      antigen on human lymphocytes. An epi-illumination fluorescence microscope was
      adapted to provide near-IR excitation using a xenon lamp for visualization of the
      visible emission. Advantages of UPT are (i) permanent, strong, anti-Stokes
      emission of discrete wavelengths; (ii) unmatched contrast in biological specimens
      due to the absence of autofluorescence upon excitation with IR light; (iii)
      simultaneous detection of multiple target analytes; and (iv) low-cost microscope
      modifications. The new methodology has not only high potential value in
      diagnostic pathology as described here, but may offer advantages for the
      detection of proteins or nucleic acids when applied to molecular biology, genomic
      research, virology, and microbiology.

PMID- 9918654
TI  - Lipid analysis by matrix-assisted laser desorption and ionization mass
      spectrometry: A methodological approach.
AB  - Whereas matrix-assisted laser desorption and ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) has gained high importance in the field of protein
      analysis, surprisingly few studies were published about the use of MALDI for
      lipid analysis. Lipids, however, are well-suited for MALDI since all experiments
      can be performed in a sole organic phase and, thus, extremely homogeneous
      matrix/analyte mixtures are formed. We report here for the first time the
      application of MALDI-TOF-MS for the analysis of diacylglycerols,
      phosphatidylcholines, and (poly)phosphoinositides. It is shown that in a matrix
      of 2,5-dihydroxybenzoic acid the molecular ions (M + 1) of phosphatidylcholines
      as well as the corresponding adducts of different phosphoinositides are easily
      detected even in complex mixtures, and thus, detailed data on the fatty acid
      composition are provided. In contrast, diacylglycerols are mainly detected as the
      corresponding sodium or potassium adducts, but not as the protonated forms.
      Fragmentation reactions of fatty acids on the double bonds and on the polar lipid
      head group are observed to a minor extent in the spectra of all investigated
      lipids. Generally, choline derivatives are most sensitive toward further
      fragmentation reactions. Due to its very high sensitivity (up to picomolar
      concentrations) MALDI-TOF-MS can be used for the direct investigation of
      biologically relevant lipid mixtures occurring, e.g. , in cell membranes. The
      analysis of the lipid composition of neutrophilic granulocytes is given as a
      representative example for future applications.

PMID- 9918655
TI  - Carbamylation of cysteine: a potential artifact in peptide mapping of hemoglobins
      in the presence of urea.
AB  - Peptide mapping is a useful technique for identifying posttranslational
      modifications. However, sometimes artifacts can be introduced during the mapping
      procedure which can be misleading in identifying the origin and nature of the
      modifications. During peptide mapping of unalkylated hemoglobins with
      Staphylococcus aureus V8 proteinase, we found a significant level of carbamylated
      cysteines. Carbamylation was not detected if recombinant human hemoglobin
      (rHb1.1) was alkylated prior to digestion. Our experiments indicated that this
      modification was an artifact of the digestion procedure in which the slightly
      acidic conditions promoted the reaction of cysteine sulfhydryls with residual
      cyanate derived from urea. Carbamylmercaptans were found to be stable under
      acidic conditions but were unstable in base. The extent of cysteine carbamylation
      can be moderated by the use of scavengers.

PMID- 9918656
TI  - Analyses of secondary structures in DNA by pyrosequencing.
AB  - A common problem in conventional DNA sequencing is the occurrence of DNA sequence
      compressions during gel electrophoresis, leading to misreading of the sequence.
      These compressions are usually due to secondary structures in the DNA fragment.
      In this study, we present a non-gel-based DNA sequencing technique that
      facilitates analysis of such DNA regions. A part of the polymorphic pertussis
      toxin promoter region in five different Bordetella species was successfully
      resolved by the new technique. The obtained sequence data revealed four related
      palindromic sequences. The ability of different DNA polymerases to read through
      such secondary structures is also described.

PMID- 9918657
TI  - Novel matrix descriptor for secondary structure segments in proteins:
      demonstration of predictability from circular dichroism spectra.
AB  - An extension to standard protein secondary structure predictions using optical
      spectra that encompasses the number and average lengths of segments of uniform
      secondary structure in the sequence is demonstrated. The connectivity and numbers
      of segments can be described by a matrix descriptor [sij] (i, j representing
      segment types such as helix and beta-sheet strands). Independent knowledge of the
      fractional concentration of each secondary structure type and of the total number
      of residues in the protein then with [sij] yields the average segment length of
      each type. The physical background for prediction of this extended structural
      descriptor from spectral data is summarized, rules for its generation from
      reference X-ray structures are defined, and formal variants of its form are
      discussed. Using a novel neural network approach to analyze a training set of
      electronic circular dichroism (ECD) and vibrational circular dichroism (VCD)
      spectra for 23 proteins, matrix descriptors encompassing helix, sheet, and other
      forms are predicted. The results show that the matrix descriptor can be predicted
      to an accuracy comparable to that of conventionally predicted average fractional
      secondary structures. In this respect the ECD predictions of [sij] were
      significantly more accurate than the VCD ones, which may result from the longer
      range length dependence of the ECD bandshape and intensity. Summary results for a
      parallel analysis using Fourier transform infrared spectra indicate somewhat
      lower reliability than those for VCD.

PMID- 9918658
TI  - Separation of selenium-containing proteins in human and mouse plasma using tandem
      high-performance liquid chromatography columns coupled with inductively coupled
      plasma-mass spectrometry.
AB  - An analytical method that uses two different high-performance liquid
      chromatography (HPLC) columns in tandem has been developed that separates three
      major selenium-containing proteins (albumin, glutathione peroxidase, and
      selenoprotein P) found in human blood plasma. The first column was a heparin
      affinity column and the second was a gel filtration column whose outlet was
      directly connected to an inductively coupled plasma-mass spectrometer. The method
      successfully separated plasma selenium into the three selenium-containing
      proteins and revealed the preferential retention of selenium in the form of
      selenoprotein P in a selenium-deficient human and in selenium-deficient mice. Our
      results also confirm the results of previous studies that showed a preference for
      supplemented selenium to be taken up as selenoprotein P in rats. Advantages of
      the tandem column method are that it allows rapid and convenient analyses of the
      distribution of plasma selenium, and that it is suitable for stable isotope
      tracer studies and metal interaction studies.

PMID- 9918659
TI  - High-performance liquid-phase separation of glycosides. III. Determination of
      total glucosinolates in cabbage and rapeseed by capillary electrophoresis via the
      enzymatically released glucose.
AB  - A selective and sensitive method for the determination of total glucosinolates
      (GSs) in plant extracts by capillary electrophoresis-laser-induced fluorescence
      (LIF) detection was developed. It was based on the enzymatically released glucose
      from glucosinolates in the presence of the hydrolyzing enzyme myrosinase. The
      released glucose was converted to gluconic acid (GA) by the action of glucose
      oxidase. The resulting GA was then labeled selectively with the fluorescent tag 7
      aminonaphthalene-1, 3-disulfonic acid (ANDSA). The peak area resulting from the
      GA-ANDSA derived from free and bound glucose was subtracted from the peak area of
      the GA-ANDSA resulting from the free glucose in the sample. This gave the total
      glucosinolates in the sample. The peak areas were normalized to the internal
      standard, N-acetylneuraminic acid derivatized with ANDSA. The method was
      validated using four different plant extracts, white cabbage leaves, rapeseed
      leaves, rapeseed roots, and rapeseed seeds. Furthermore, a capillary
      electrophoresis-UV detection method for profiling GS in plant extracts was
      developed. In addition to providing a fingerprint of the glucosinolates in plant
      extracts, the method allowed the experimenter to rapidly check the various steps
      involved in the extraction and sample cleanup.

PMID- 9918660
TI  - A spun-column assay for determination of leptin binding in serum.
AB  - Serum collected from 27 patients was assayed simultaneously using a spun-column
      assay (SPC) and a traditional exclusion gel-filtration assay (GFC) to determine
      specific leptin binding. The levels of serum leptin binding determined by either
      assay correlated inversely with serum leptin levels (SPC, r = 0.63, P < 0.001;
      GFC, r = 0.79, P < 0.0001). Although specific leptin binding as determined by the
      traditional exclusion gel-filtration assay was generally higher than that
      obtained by the spun-column assay (mean = 18.3% vs 14.0%, P < 0. 02,
      respectively); the values obtained between the two assay methods were highly
      correlative (r = 0.89, P < 0.0001). By varying either the amount of 125I-leptin
      or the amount of competitor, analysis was carried out using the spun-column assay
      to determine the intrinsic properties of serum leptin binding. Results yielded a
      Kd = 0.3 nM, where each variable amount of leptin or competitor was carried out
      in duplicate. The complete analysis was carried out in the time that it typically
      takes for a single sample determination by the traditional exclusion gel
      filtration assay. We conclude that the "spun-column" assay is a useful method for
      rapid and accurate quantification of leptin binding in serum.

PMID- 9918661
TI  - Quantitative determination of globotriaosylceramide by immunodetection of
      glycolipid-bound recombinant verotoxin B subunit.
AB  - An assay for the neutral glycosphingolipid, globotriaosylceramide (Galalpha1
      4Galbeta1-4Glcbeta1-1Cer; GL-3), was developed based on the B subunit of
      Escherichia coli verotoxin (VTB). The VTB gene was isolated, overexpressed in E.
      coli, and purified by a single immunoaffinity chromatographic step using a
      monoclonal anti-VTB IgG-agarose column. Purified recombinant VTB was used to
      develop an enzyme-linked immunosorbent assay (ELISA) to determine the GL-3
      concentrations in plasma and tissue extracts from normal individuals and patients
      and mice with alpha-galactosidase A deficiency (human Fabry disease). The mean
      (+/-1 SD) plasma GL-3 concentrations in affected male and female heterozygotes
      with Fabry disease were 12.6 +/- 3.7 and 1.1 +/- 0.7 microg/ml, respectively,
      whereas normal individuals had 0.9 +/- 0.4 microg/ml. In 5- to 6-month-old mice
      with alpha-galactosidase A deficiency, the average GL-3 concentrations in spleen,
      kidney, liver, heart, and plasma were 2790 +/- 400, 1100 +/- 93, 378 +/- 67, and
      196 +/- 28 ng/mg wet wt and 5. 1 +/- 2.0 microg/ml, respectively, whereas tissues
      from wild-type mice contained very low or undetectable GL-3 levels. This ELISA
      assay should prove useful for determining the GL-3 levels, as well as for
      monitoring the effectiveness of therapeutic endeavors in patients with Fabry
      disease.

PMID- 9918662
TI  - Glucose sensor for low-cost lifetime-based sensing using a genetically engineered
      protein.
AB  - We describe a glucose sensor based on a mutant glucose/galactose binding protein
      (GGBP) and phase-modulation fluorometry. The GGBP from Escherichia coli was
      mutated to contain a single cysteine residue at position 26. When labeled with a
      sulfhydryl-reactive probe 2-(4'-iodoacetamidoanilino)naphthalene-6-sulfonic acid,
      the labeled protein displayed a twofold decrease in intensity in response to
      glucose, with a dissociation constant near 1 microM glucose. The ANS-labeled
      protein displayed only a modest change in lifetime, precluding lifetime-based
      sensing of glucose. A modulation sensor was created by combining ANS26-GGBP with
      a long-lifetime ruthenium (Ru) metal-ligand complex on the surface of the
      cuvette. Binding of glucose changed the relative intensity of ANS26-GGBP and the
      Ru complex, resulting in a dramatic change in modulation at a low frequency of
      2.1 MHz. Modulation measurements at 2.1 MHz were shown to accurately determine
      the glucose concentration. These results suggest an approach to glucose sensing
      with simple devices.

PMID- 9918663
TI  - Continuous beds for microchromatography: chromatofocusing and anion exchange
      chromatography.
AB  - A method was developed for the preparation of continuous beds derivatized with
      polyethyleneimine (PEI) for chromatofocusing and anion exchange chromatography in
      the capillary mode. First, a continuous bed activated by epoxy groups was
      synthesized inside a fused silica capillary and became at the same time
      covalently attached to the inner wall of the capillary. A PEI solution was then
      pumped through the continuous bed to allow the imine groups in PEI to react with
      the epoxy groups in the bed. Efficient immobilization of PEI was indicated by the
      high-resolution separation of standard proteins (hemoglobins C, S, F, and A) in
      both chromatofocusing and anion exchange chromatography on a capillary column
      prepared by this method.

PMID- 9918664
TI  - Peptide mapping and disulfide bond analysis of myeloid progenitor inhibitory
      chemokine and keratinocyte growth factor by matrix-assisted laser desorption
      ionization mass spectrometry.
AB  - Peptide mapping and matrix-assisted laser desorption ionization mass spectrometry
      (MALDI-MS) were conducted to characterize the human genome-based recombinant
      proteins. Accurate mass values for the deleted forms of the myeloid progenitor
      inhibitory factor chemokine (MPIF-1d23), and the keratinocyte growth factor (KGF
      2d33) were measured as 8848.55 +/- 0.25 and 16,175.87 +/- 0.89 Da, respectively.
      The mass accuracy of delayed ion extraction MALDI-MS measurements was within 20
      ppm of the cDNA predicted value. Reduction and alkylation of the chemokine showed
      the presence of six cysteine residues and three disulfide bonds. Additional
      confirmation of disulfide bonding among the cysteine residues of the chemokine
      was demonstrated by identifying the RP-HPLC separated tryptic and endoprotease
      Glu-C peptides. Three methionine residues of the chemokine were identified by
      MALDI-MS of its cyanogen bromide (CNBr) cleavage products. The KGF-2d33 growth
      factor, however, lacked the disulfide bonding between the two-cysteine residues
      and contained two free sulfhydryl groups. Direct analysis of the growth factor
      CNBr digest showed 7542.99, 4993.4, and 3107.7 Da peptides, which identified the
      methionine residues. Peptide mapping mass spectrometry indicated that host
      specific posttranslational modifications had not influenced the gene expression
      work.

PMID- 9918665
TI  - Time-resolved photolabeling of membrane proteins: application to the nicotinic
      acetylcholine receptor.
AB  - An apparatus has been developed that allows photoaffinity ligands to be crossed
      linked to milligram quantities of membrane proteins with maximum attainable yield
      following contact times of approximately 1 ms. The apparatus consisted of three
      parts: a conventional rapid mixing unit, a novel freeze-quench unit, and a
      photolabeling unit. The freeze-quench unit consisted of a rapidly rotating metal
      disk which was precooled in liquid nitrogen. Correct alignment of the exit jet
      from the sample mixer allowed up to 2 ml of sample to be frozen in a thin film on
      the disk. Experiments with colorimetric reactions showed the combined dead time
      of mixing and freeze-quenching to be submillisecond. Photoincorporation was
      maximized by prolonged irradiation of the freeze-quenched sample. Using this
      apparatus we determine the binding kinetics of the resting state channel
      inhibitor 3-[125I](trifluoromethyl)-3-(m-iodophenyl) diazirine (TID) to nicotinic
      acetylcholine receptor-rich membranes from Torpedo. The binding kinetics for the
      125I-labeled alpha and delta subunits were biphasic; about half the binding was
      complete by 2.4 ms, and the remainder could be resolved and occurred with a
      pseudo-first-order rate constant determined at 4 microM [125I]TID of 12.0 +/- 2.3
      and 13.6 +/- 4.0 s-1, respectively. This compares well to the same constant
      determined for the inhibition of agonist-induced cation flux in Torpedo
      membranes.

PMID- 9918666
TI  - Ferrocene-conjugated m-phenylenediamine conducting polymer-incorporated
      peroxidase biosensors.
AB  - The development and characteristics of a reagentless amperometric biosensor
      employing horseradish peroxidase incorporated in an electrochemically deposited
      ferrocene-modified phenylenediamine film on a glassy carbon electrode is
      reported. The horseradish peroxidase/poly(m-aminoanilinomethylferrocene)-
      modified glassy carbon electrode reagentless biosensor measured hydrogen peroxide
      and other organic peroxides in both aqueous and organic medium by reduction at a
      low applied potential of -0.05 V (vs Ag/AgCl) without interference from molecular
      oxygen. When modified with glucose oxidase, the new bienzyme electrode measured
      glucose sensitively and selectively, demonstrating the suitability of the above
      peroxide biosensor for other oxidoreductase enzyme-based biosensors.

PMID- 9918667
TI  - Protein identification using 20-minute Edman cycles and sequence mixture
      analysis.
AB  - We have developed a 20-min Edman cycle and a multiple sample horizontal flow
      reactor for the sequence analysis of PVDF-electroblotted proteins. The 20-min
      cycle uses a 12-min C18 phenylthiohydantoin separation. This cycle and separation
      is compatible with most Applied Biosystems sequencers. Using this rapid cycle, 10
      residues on six different proteins can be completed within a 24-h period. We also
      demonstrate the use of an algorithm that can sort mixture sequences derived from
      PVDF bands that contain coeluting proteins.

PMID- 9918668
TI  - Quantification of bacterial lipopolysaccharides by the purpald assay: measuring
      formaldehyde generated from 2-keto-3-deoxyoctonate and heptose at the inner core
      by periodate oxidation.
AB  - We have adapted the purpald assay (M. S. Quesenberry and Y. C. Lee, Anal.
      Biochem. 234, 50-55, 1996) to quantify lipopolysaccharide (LPS) content in
      solution in 96-well microtiter plates at room temperature. This method employs
      the oxidation of unsubstituted terminal vicinal glycol groups in 2-keto-3
      deoxyoctonate (Kdo) and l-(or d-)glycero-d-manno-heptose of LPS molecules by
      periodate to release formaldehyde. The formaldehyde is quantified at 550 nm (or
      530-570 nm) by reacting with purpald reagent followed by oxidation with NaIO4.
      The sensitivity of the purpald assay is comparable to that of the Kdo assay for
      LPS determination. However, the purpald assay is superior to the Kdo assay
      because: (i) No acid hydrolysis of the samples and no boiling in the assay
      process are required; thus, it can be directly carried out with microtiter plates
      for a large number of samples at room temperature. (ii) The purpald assay can
      detect many types of LPS from various bacteria since LPS contains Kdo and heptose
      which possess unsubstituted terminal vicinal glycol in its structure, while the
      Kdo assay cannot detect LPS from certain bacteria (e.g., Haemophilus influenzae,
      Bordetella pertussis, and Vibrio cholerae) due to substitution at the C-4 and C-5
      positions of Kdo.

PMID- 9918670
TI  - Selectivity and sensitivity of fluorescence lifetime-based metal ion biosensing
      using a carbonic anhydrase transducer.
AB  - A key performance criterion for metal ion determinations in complex media like
      serum, cytoplasm of the cell, and sea water is selectivity: the ability to
      determine the analyte(s) of interest, in the presence of relatively high
      concentrations of interferents. Cu(II), Zn(II), Cd(II), Co(II), and Ni(II) may be
      determined by changes they induce in the fluorescence lifetime and intensity of
      site-specifically labeled fluorescent variants of apocarbonic anhydrase II. Free
      metal ion concentrations in the picomolar range (for Cu(II) and Zn(II)) and the
      nanomolar range (for Cd(II), Co(II), and Ni(II)) were determined, based on the
      affinity of the apoenzyme for these ions. Mg(II) at 50 mM and Ca(II) at 10 mM
      produced no effect. By the use of different fluorescent labels, transducers were
      made which responded well to Cu(II), Co(II), and Ni(II), but not to Zn(II) and
      Cd(II), and vice versa.

PMID- 9918669
TI  - Spontaneous alpha-N-6-phosphogluconoylation of a "His tag" in Escherichia coli:
      the cause of extra mass of 258 or 178 Da in fusion proteins.
AB  - Several proteins expressed in Escherichia coli with the N-terminus Gly-Ser-Ser
      [His]6- consisted partly (up to 20%) of material with 178 Da of excess mass,
      sometimes accompanied by a smaller fraction with an excess 258 Da. The
      preponderance of unmodified material excluded mutation, and the extra masses were
      attributed to posttranslational modifications. As both types of modified protein
      were N-terminally blocked, the alpha-amino group was modified in each case.
      Phosphatase treatment converted +258-Da protein into +178-Da protein. The
      modified His tags were isolated, and the mass of the +178-Da modification
      estimated as 178.06 +/- 0.02 Da by tandem mass spectrometry. As the main
      modification remained at +178 Da in 15N-substituted protein, it was deemed
      nitrogen-free and possibly carbohydrate-like. Limited periodate oxidations
      suggested that the +258-Da modification was acylation with a 6-phosphohexonic
      acid, and that the +178-Da modification resulted from its dephosphorylation. NMR
      spectra of cell-derived +178-Da His tag and synthetic alpha-N-d-gluconoyl-His tag
      were identical. Together, these results suggested that the +258-Da modification
      was addition of a 6-phosphogluconoyl group. A plausible mechanism was acylation
      by 6-phosphoglucono-1,5-lactone, produced from glucose 6-phosphate by glucose-6
      phosphate dehydrogenase (EC 1.1.1.49). Supporting this, treating a His-tagged
      protein with excess d-glucono-1,5-lactone gave only N-terminal gluconoylation.

PMID- 9918671
TI  - A method for determining the cytoprotective effect of catalase in transiently
      transfected cell lines and in corneal tissue.
AB  - Both when developing gene constructs for therapeutic purposes and when testing
      the biological function of proteins, it would be convenient to use cells or
      tissues that have been transiently transfected with the gene of interest.
      However, determining the protective effects of transient gene expression is
      complicated by a low transfection efficiency, resulting in only a minority of the
      cells expressing the introduced gene and consequently a reduced sensitivity of
      assays measuring the death of transfected cells. In this study we have developed
      a convenient technique for determining cell death in transiently transfected
      vascular endothelial cell monolayers and in corneal tissue. Vascular endothelial
      cells were cotransfected with human catalase cDNA and the lacZ gene encoding beta
      galactosidase, under conditions in which cells expressing beta-galactosidase also
      expressed catalase. By assaying release of beta-galactosidase upon cell death, it
      was possible to show that catalase transfection led to significant protection
      against the cytotoxic effect of increasing concentrations of hydrogen peroxide.
      The assay was adapted to demonstrate the protective effects of catalase
      transfection on hydrogen peroxide-mediated injury of intact corneal endothelium
      under ex vivo culture conditions. This assay should also be useful for
      characterizing the cytoprotective effects of other genes in transient
      transfection systems.

PMID- 9918673
TI  - Quantitative determination of cardiolipin in mitochondrial electron transferring
      complexes by silicic acid high-performance liquid chromatography.
AB  - Quantitative determination of cardiolipin from two mitochondrial electron
      transferring complexes was achieved using a rapid and sensitive silicic acid HPLC
      method combined with digital analysis of the elution profile. Phospholipid
      samples containing as little as 0. 01 nmol of cardiolipin were accurately
      analyzed. Phospholipids from detergent-solubilized cytochrome bc1 (EC 1.10.2.2)
      and cytochrome c oxidase (EC 1.9.3.1) were extracted by an organic two-phase
      system and analyzed by isocratic normal-phase HPLC after dissolving the dried
      sample in the mobile phase (cyclohexane:2-propanol:5 mM phosphoric acid,
      50:50:2.9, v/v/v). Analysis was performed by the method of standard addition in
      which increasing amounts of cardiolipin (0 to 5 nmol) are added to a constant
      amount of phospholipid extract containing an unknown amount of cardiolipin. By
      determining the slope and intercept of a plot of the HPLC elution peak area as a
      function of the amount of standard cardiolipin added, the amount of cardiolipin
      in the unknown is determined. By this analysis, purified, detergent-solubilized
      bovine heart cytochrome bc1 and cytochrome c oxidase contained 9.2 +/- 0.7 and
      3.05 +/- 0.05 mol cardiolipin per mole of enzyme, respectively. The method was
      also used to prove that cardiolipin could be completely removed from each complex
      by digestion with Crotalus atrox phospholipase A2, i.e., each delipidated complex
      contained less than 0.05 mol cardiolipin per mole of complex. The rapidity and
      high sensitivity of this method make it very useful for analysis of cardiolipin
      in other biological samples.

PMID- 9918672
TI  - Quantitation of alpha2u-globulin in rat kidney cytosol by capillary
      electrophoresis.
AB  - The renal accumulation of alpha2u-globulin has been implicated in the
      tumorigenicity of many nongenotoxic chemicals to the kidney of the male rat.
      Several chemicals inducing renal tumors in the male rat were shown to bind to
      alpha2u-globulin. This binding impairs the renal degradation of alpha2u-globulin,
      resulting in lysosomal overload, cell death, increased cell proliferation, and,
      presumably, renal tumor formation. To support the role of alpha2u-globulin
      accumulation in the renal toxicity of a chemical, a demonstration of the
      accumulation of this protein in the kidney of the male rat is one prerequisite.
      Monoclonal antibodies to alpha2u-globulin are available for quantifying alpha2u
      globulin content; however, the procedure is time-consuming and complicated. We
      developed a method for the quantitation of alpha2u-globulin in renal cytosol
      using capillary electrophoresis. Renal cytosol fractions were analyzed by
      capillary electrophoresis as protein-SDS complexes. Using alpha2u-globulin
      purified from urine of male rats, the limit of detection was 10 microg/ml sample
      in routine analyses. Excellent run to run reproducibility in migration time (CV
      </= 4%) and peak areas corresponding to alpha2u-globulin (CV </= 3%) after
      normalization to the internal standard was observed. Significant increases in
      renal alpha2u-globulin content (up to 85% of total protein content) compared to
      controls (approx 15%) were observed in kidney cytosol of rats treated with
      alpha2u-globulin nephropathy-inducing agents such as trimethylpentane or the
      alkylphosphonates dimethyl methylphosphonate and diethyl ethylphosphonate, but
      not in kidney cytosol of male rats treated with tris-(2-chloroethyl)phosphate or
      the nephrotoxic agent hexachlorobutadiene. A good correlation of the alpha2u
      globulin contents determined by capillary electrophoresis and immunoblotting with
      an alpha2u-globulin-specific antibody (r2 = 0.997) was obtained. Capillary
      electrophoresis provides a simple, rapid, and highly reproducible quantitation of
      alpha2u-globulin accumulation for renal tumorigens and may assist in the risk
      assessment process for these chemicals.

PMID- 9918675
TI  - Quantification of hyaluronan and chondroitin/dermatan sulfates in the tissue
      sections on glass slides.
AB  - The method for the determination of hyaluronan and chondroitin/dermatan sulfates
      in the tissue sections on a glass slide, which were prepared by histological
      technique, was established by applying to porcine skin. The degradation of these
      glycosaminoglycans to the unsaturated disaccharides in porcine skin sections on a
      glass slide was achieved by chondroitinase ABC and ACII in the presence of highly
      purified bacterial collagenase. Subsequently, the resulting unsaturated
      disaccharides were determined by HPLC with fluorometric postcolumn derivatization
      using 2-cyanoacetamide as a reagent. So far, the determination of the
      glycosaminoglycans in the tissues has taken up more than 5 days, whereas the
      determination of the glycosaminoglycans in the frozen sections by the present
      method was completed within a day. In addition, applications of the present
      method to the serial polyester wax sections processed with a small surgical knife
      made it possible to determine the glycosaminoglycans in a local part in the
      tissue section. The present method should open a way for the clinical analysis of
      glycosaminoglycans in the pathological tissue samples.

PMID- 9918674
TI  - A one-step method for protein estimation in biological samples: nitration of
      tyrosine in nitric acid.
AB  - A number of methods are commonly employed for the determination of protein in
      biological samples. Unfortunately, several compounds that are constituents of
      biological buffers interfere with these methods, limiting their application.
      Previous studies have demonstrated that tyrosine rapidly undergoes nitration in
      nitric acid to yield 3-nitrotyrosine, which has a lambdamax of 358 nm. Utilizing
      this reaction, we have developed a one-step method for the assessment of protein
      content in biological samples. Common interfering substances, including SDS,
      urea, glycerol, ammonium sulfate, and beta-mercaptoethanol, do not interfere with
      this method. Because of its simplicity, this reaction might be useful for
      estimating protein content in a variety of biological samples.

PMID- 9918676
TI  - A high-yield, enzymatic synthesis of GDP-D-[3H]arabinose and GDP-L-[3H]fucose.
AB  - For assays involving glycosyltransferases or transporters, several GDP-sugars are
      either commercially unavailable or expensive. We describe an enzymatic synthesis
      of GDP-d-[3H]arabinosep and GDP-l-[3H]fucose that yields 66-95% nucleotide-sugar
      from the appropriate radiolabeled sugar in less than 30 min. The coupled reaction
      requires Mg2+, ATP, and GTP along with the appropriate radioactive
      monosaccharide, sugar-1-kinase, and pyrophosphorylase. The latter two activities
      are present in a cytosolic fraction of Crithidia fasciculata, which is easily
      grown at room temperature in simple culture medium without serum or added CO2.
      Addition of commercial yeast inorganic pyrophosphatase shifts the equilibrium of
      the pyrophosphorylase reaction toward nucleotide-sugar formation. To verify that
      these nucleotide-sugars are biologically active, we tested their ability to serve
      as substrates for glycosyltransferases. GDP-l-[3H]fucose functions as the donor
      substrate for recombinant human fucosyltransferase V, and GDP-d-[3H]arabinosep
      serves as the donor substrate for the arabinosyltransferase activities present in
      Leishmania major microsomes.

PMID- 9918677
TI  - Phage recovery by electroporation of naked DNA into host cells avoids the use of
      packaging extracts.
AB  - In this paper, we describe the application of electroporation to deliver phage
      DNA into bacterial cells in order to recover it as phage particles. The
      methodology represents a quicker and cheaper alternative to the use of packaging
      extracts to rescue phage clones stored as naked DNAs. Furthermore, our data
      demonstrate that there were not rearrangements or recombinations between phage
      DNAs when a mixture of different DNAs was electroporated, suggesting the use of
      electroporation as a reliable method for construction of gene libraries.

PMID- 9918678
TI  - Adaptation of the protein kinase filter paper assay to a 96-well microtiter
      format.

PMID- 9918679
TI  - Detection by the lectins from Maackia amurensis and Sambucus nigra of 3- and 6
      linked sialic acid in gangliosides with neolacto chains separated on thin-layer
      chromatograms and blotted to PVDF membranes.

PMID- 9918680
TI  - Generation of microgram quantities of trinucleotide repeat tracts of defined
      length, interspersion pattern, and orientation.

PMID- 9918681
TI  - Carbohydrate-bearing cell surface receptors involved in innate immunity:
      interleukin-12 induction by mitogenic and nonmitogenic lectins.
AB  - Based on the observation that pathogen-derived lectins play an important role in
      cell adhesion and invasion, we examined the possible role of host carbohydrate
      bearing molecules in inducing the secretion of IL-12, a crucial proinflammatory
      cytokine. The ability of 12 plant lectins to recognize and stimulate naive murine
      mononuclear cells in vitro has been characterized in this study. Mitogenic
      lectins (comprising Con A, PHA, PSA, and LCA) were found to induce the secretion
      of multiple cytokines in vitro, including IL-2, interferon (IFN)-gamma, and IL
      12. Of interest, WGA, a nonmitogenic lectin unable to promote IL-2 secretion, was
      found to induce IL-12 and IFN-gamma production in a T and B cell-independent
      fashion. The functional properties of WGA were inhibited by N-acetylneuraminic
      acid and N,N'-diacetylchitobiose. WGA therefore represents a potentially useful
      tool for the study of membrane glycoproteins involved in the early
      proinflammatory response characteristic of innate immunity.

PMID- 9918682
TI  - Modulation of TH1 and TH2 cytokine production with the immune response modifiers,
      R-848 and imiquimod.
AB  - Cytokines produced by antigen-presenting cells are known to affect the
      development and cytokine profile of T cells. The immune response modifiers
      imiquimod and R-848 were previously shown to stimulate human and mouse cultures
      to secrete interferon-alpha. Results from the present study demonstrate that R
      848 and imiquimod are capable of inducing interleukin-12 and interferon-gamma in
      mouse and human cell cultures. Both CD4(+) and CD8(+) T lymphocytes were
      responsible for producing IFN-gamma following stimulation with R-848. Macrophages
      were required for induction of interferon-gamma by R-848 and the cytokines IFN
      alpha and IL-12 mediated this response. R-848 and imiquimod were also found to
      inhibit IL-4 and IL-5 production in mouse and human culture systems. The
      inhibition of IL-5 in response to R-848 is seen in cultures containing CD4(+)
      lymphocytes and macrophages and is mediated in part by IFN-alpha. These data
      suggest that imiquimod and R-848 may have clinical utility in diseases where cell
      mediated immune responses are important and in diseases associated with
      overexpression of IL-4 or IL-5 such as atopic disease.

PMID- 9918683
TI  - Tetanus toxin impairs accessory and secretory functions in interferon-gamma
      treated murine macrophages.
AB  - Tetanus neurotoxin (TT), a product of microbial origin, acts as a zinc
      endopeptidase on vesicle-associated membrane proteins (VAMP). We have
      demonstrated that TT displays inhibitory effects on secretory and accessory
      functions in the murine macrophage (Mphi) cell line GG2EE. Nitric oxide (NO)
      secretion was decreased when interferon (IFN)-gamma-pretreated GG2EE Mphis were
      coincubated with a fungal costimulus (SMP200) and TT. When heat-inactivated TT
      was used this effect was not evident. The TT-mediated phenomenon was dose
      dependent and specific since, under the same experimental conditions, it did not
      affect interleukin-6 or tumor necrosis factor-alpha secretion. Furthermore, IFN
      gamma-induced major histocompatibility complex class II molecule expression and
      GG2EE accessory function, assessed by SMP200-stimulated lymphoproliferation, were
      also inhibited by TT. Such inhibition was incomplete, in line with our previous
      results showing that TT partially cleaves VAMP proteins in murine M&phi;.

PMID- 9918684
TI  - Placental protein 14 functions as a direct T-cell inhibitor.
AB  - Human placental protein 14 (PP14, also referred to as glycodelin and progesterone
      associated endometrial protein) inhibits phytohemagglutinin (PHA)-stimulated T
      cell proliferation and monokine secretion within PBMC populations. However, the
      mechanisms underlying these and other PP14 immunoinhibitory activities remain
      unclear. In the present study, we asked whether PP14's T-cell inhibitory effect
      is a direct one or, alternatively, an indirect consequence of accessory cell (AC)
      perturbation. Using either immunopurified PP14 or first-trimester amniotic fluid
      (AF) as a rich source of PP14, we documented inhibition of the proliferation of
      highly purified peripheral blood T-cells when stimulated with anti-CD3 mAbs or
      PHA in the presence of paraformaldehyde-fixed AC. Significantly, PP14 inhibited T
      cell proliferation and IL-2 secretion induced by immobilized anti-CD3 and anti
      CD28 mAbs in the absence of AC. PP14 depletion (via immunoprecipitation)
      abrogated AF's T-cell inhibitory activity, indicating that the PP14 within the
      amniotic fluid is required for this immunoregulatory effect. These findings
      establish that PP14 can inhibit T-cell proliferation in the absence of AC and
      thus add PP14 to the relatively restricted set of immunoinhibitory proteins that
      are known to target T-cells directly. Additional data demonstrate that PP14's
      inhibitory effect can be overridden by stimuli which circumvent early events
      during T-cell receptor (TCR) activation, namely, protein kinase C activators in
      combination with Ca2+ ionophores. These latter results suggest that PP14 inhibits
      early events in the TCR signaling pathway.

PMID- 9918685
TI  - Enkephalin receptors and receptor-mediated signal transduction in cultured human
      lymphocytes.
AB  - Enkephalins are opioid peptides that bridge the neuroendocrine and immune
      systems. Using flow cytometry and a fluorescein conjugate of the endogenous
      pentapeptide methionine-enkephalin (ME), we have identified enkephalin receptors
      on cultured human lymphocytes. Cell surface recognition sites that bound ME with
      high affinity and specificity were detected for NALM 6 (pre-B acute lymphoblastic
      leukemia) and Jurkat (T lymphoma) cells. Brain-like enkephalin receptors were
      measured for these lymphocytes using conventional radioligand-receptor assays and
      the highly delta opioid receptor-selective enkephalin analog [3H]DPDPE. Upon
      activation, the lymphocyte enkephalin receptors transmitted signals that enhanced
      the accumulation of intracellular cAMP. These studies provide evidence that
      cultured human lymphocytes of the B (NALM 6 cells) and T (Jurkat cells) lineages
      express functional enkephalin receptors and suggest that such receptors may be
      instrumental in the lymphocyte response to opioid peptides and alkaloids.

PMID- 9918686
TI  - An inhibitor of CD28-CD80 interactions impairs CD28-mediated costimulation of
      human CD4 T cells.
AB  - We have identified and characterized a microbial extract-derived inhibitor of T
      cell CD28-dependent costimulation, NP1835-2, utilizing an in vitro system in
      which anti-human CD3 antibody and a human CD80-Ig fusion protein are immobilized
      on protein A-coated microspheres. This system is CD28-CD80-dependent, as judged
      by the specific ability of anti-CD80 antibody or cytotoxic T lymphocyte antigen-4
      Ig to block human CD4 T cell responses. Activation of CD4 T cells in this system
      in presence of NP1835-2 resulted in a concentration-dependent inhibition of T
      cell proliferation (IC50 of 1-4 microg/ml), surface activation marker expression,
      and the production of many T cell cytokines, with the exception of TGFbeta.
      Impairment of T cell activation correlated with a blockade of cell cycle
      progression at G0/G1 and was only partly restored by addition of 100 U/ml IL-2.
      No inhibition by NP1835-2 of T cell proliferation stimulated by plate-bound anti
      CD3 antibody, phorbol 12-myristate 13-acetate + A23187, or P815 cells expressing
      the costimulatory molecule CD58 was observed. NP1835-2 was unable to modulate
      anti-IgM-stimulated B cell proliferation or LPS-induced monocyte activation.
      Suboptimal concentrations of NP1835-2 and cyclosporin together were able to
      impair T cell activation in an additive fashion. NP1835-2 was also able to
      inhibit the primary human MLR. These data indicate that NP1835-2 may belong to a
      class of molecules capable of selectively impairing CD28-mediated T cell
      costimulation and suggest its potential usefulness in the treatment of a variety
      of T cell-dependent diseases. Moreover, NP1835-2 may serve as a useful probe for
      investigating the mechanisms involved in T cell nonresponsiveness.

PMID- 9918687
TI  - Characterization of B lymphocytes rescued from apoptosis by platelet-activating
      factor.
AB  - B lymphocyte development is characterized by deletion via apoptosis of immature
      cells that are insufficiently stimulated. We have previously demonstrated that
      crosslinking of the B cell receptor (BCR) using anti-IgM antibodies (alphaIgM) (2
      microg/ml) in Ramos B lymphoblastoid cells causes deletion of 30-40% of cells by
      apoptosis in 24 h. Addition of the potent lipid mediator platelet-activating
      factor (10(-7) M) to alphaIgM stimulated Ramos cells significantly decreases the
      number of apoptotic cells as measured by annexin V labeling. We have
      characterized the phenotype of Ramos cells that have not become apoptotic
      following BCR stimulation. In these cells, there is a significant decrease in the
      surface expression of the VLA-4 adhesion molecule (31% of control expression) and
      surface IgM expression (sIgM) (53% of control expression). Significantly fewer
      cells co-incubated with platelet-activating factor (PAF) underwent apoptosis, and
      the remaining cells maintained control levels of VLA-4 (104% of control
      expression) and sIgM expression (104% of control). All of these protective
      effects were inhibited by the specific PAF receptor antagonist, WEB 2170. The
      action of PAF on alphaIgM induced apoptosis was not inhibited by either
      cycloheximide or cytochalasin B, suggesting that de novo protein synthesis and F
      actin polymerization were not implicated in the rescue of Ramos cells by PAF. In
      contrast, the ability of PAF to maintain sIgM and VLA-4 expression at control
      levels was inhibited by cycloheximide (7. 5 microg/ml). Cytochalasin B (5
      microg/ml) had no effect on sIgM expression but blocked the decrease in VLA-4
      expression mediated by alphaIgM. These data indicate that PAF's effect on
      rescuing and maintaining alphaIgM stimulated Ramos B cells is mediated via at
      least two pathways. Abrogation of apoptosis does not require de novo protein
      synthesis, while maintenance of sIgM and VLA-4 expression requires protein
      synthesis.

PMID- 9918688
TI  - Rheumatoid factor B cell tolerance via autonomous Fas/FasL-independent apoptosis.
AB  - Normal individuals do not express the high-affinity autoantibodies specific for
      self-IgG (rheumatoid factors, RF) that are commonly seen in rheumatoid arthritis
      patients. Studies of transgenic mice expressing a human IgM rheumatoid factor
      have shown that one mechanism by which higher affinity RF B cells are tolerized
      to IgG is through abortive RF B cell activation followed by deletion in the
      absence of T cell help. We show that RF B cell deletion occurs through an
      intrinsic apoptotic mechanism that is independent of the Fas/FasL pathway and
      does not involve active killing by T cells, as it occurs in RAG-1-deficient RF
      transgenic mice to the same extent as in the parental RF transgenic line.

PMID- 9918689
TI  - Antibody-independent protective mucosal immunity to gastric helicobacter
      infection in mice.
AB  - Helicobacter pylori infection of the gastric mucosa can result in gastritis and
      peptic ulcer disease. Although vaccination can induce protective immunity in
      animal models of Helicobacter infection, the mechanism(s) of protective immunity
      has not been fully elucidated. This study was designed to determine whether
      humoral immune responses are required for protective Helicobacter immunity. IgA
      deficient or immunoglobulin-deficient mice were orally immunized against
      Helicobacter felis and then challenged with live H. felis. Both groups were
      protected at levels comparable to that of wild-type mice. Additionally,
      inflammation was equivalent in extent and character between wild-type and
      antibody-deficient mice. Therefore antibody-independent mechanisms of immunity
      can protect mice against gastric Helicobacter infection.

PMID- 9918691
TI  - Translational recruitment of Xenopus maternal mRNAs in response to poly(A)
      elongation requires initiation factor eIF4G-1.
AB  - Xenopus oocytes accumulate maternal mRNAs which are then recruited to ribosomes
      during meiotic cell cycle progression in response to progesterone and coincident
      with poly(A) elongation. Prior to stimulation, most protein synthesis (
      approximately 70%) does not require intact translation factor eIF4G (B. D. Keiper
      and R. E. Rhoads, 1997, Nucleic Acids Res. 25, 395-402). In the present study we
      have addressed the requirement of eIF4G in the recruitment of mRNAs during
      meiosis. Cleavage of eIF4G by coxsackievirus protease 2A inhibited progesterone
      induced meiotic progression in 88% of the oocytes; prevented the recruitment of
      maternal mRNAs encoding cyclin B1, c-Mos, D7, and B9; and disrupted the
      association of eIF4G with poly(A)-binding protein. Poly(A) elongation, however,
      was not inhibited by eIF4G cleavage. Injection of MPF restored meiotic cell cycle
      progression to >60% of the oocytes but not the recruitment of cyclin B1 or B9
      mRNA. Previously recruited maternal mRNAs were removed from polyribosomes
      following subsequent cleavage of eIF4G, indicating that eIF4G is required both to
      recruit and also to maintain maternal mRNAs on polyribosomes. The expression of a
      cleavage-resistant variant of human eIF4G-1 (G486E) significantly restored the
      ability to synthesize c-Mos in response to progesterone and to translate
      exogenous beta-globin mRNA, indicating that the inhibition by protease 2A is due
      to cleavage of eIF4G alone. These results indicate that intact eIF4G is required
      for the poly(A)-dependent recruitment of several maternal mRNAs (cyclin B1, c
      Mos, D7, and B9) during meiotic cell cycle progression but not for the synthesis
      of most proteins.

PMID- 9918692
TI  - RNA-Mediated interference of a cdc25 homolog in Caenorhabditis elegans results in
      defects in the embryonic cortical membrane, meiosis, and mitosis.
AB  - The CDC25 dual-specificity phosphatase family has been shown to play a key role
      in cell cycle regulation. The phosphatase activity of CDC25 drives the cell cycle
      by removing inhibitory phosphates from cyclin-dependent kinase/cyclin complexes.
      Although the regulation of CDC25 phosphatase activity has been elucidated both
      biochemically and genetically in other systems, the role of this enzyme during
      development is not well understood. To examine the expression pattern and
      function of CDC25 in Caenorhabditis elegans, we characterized a cdc25 homolog,
      cdc-25.1, during early embryonic development. The CDC-25.1 protein localizes to
      oocytes, embryonic nuclei, and embryonic cortical membranes. When the expression
      of CDC-25.1 was disrupted by RNA-mediated interference, the anterior cortical
      membrane of fertilized eggs became very fluid during meiosis and subsequent
      mitotic cell cycles. Mispositioning of the meiotic spindle, defects in polar body
      extrusion and chromosome segregation, and abnormal cleavage furrows were also
      observed. We conclude that CDC-25.1 is required for a very early developmental
      process-the proper completion of meiosis prior to embryogenesis.

PMID- 9918693
TI  - Expression and function of Gdf-5 during digit skeletogenesis in the embryonic
      chick leg bud.
AB  - Bone morphogenetic proteins (BMPs) constitute a large family of secreted signals
      involved in the formation of the skeleton but the specific function of each
      member of this family remains elusive. GDF-5 is a member of the BMP family which
      has been implicated in several skeletogenic events including the induction and
      growth of the appendicular cartilages, the determination of joint forming
      regions, and the establishment of tendons. Here, we have studied the function of
      GDF-5 in digit skeletogenesis by analyzing the effects of its local
      administration in the developing autopod of embryonic chick and the regulation of
      its pattern of gene expression by other signals involved in digit morphogenesis.
      As reported in the mouse, the gdf-5 gene exhibits a precise distribution in the
      joint-forming regions of the developing chicken digital rays. GDF-5 beads
      implanted at the tip of the digits promote intense cartilage growth and fail to
      induce morphological or molecular signs of joint formation. Furthermore, GDF-5
      beads implanted in the interdigits inhibit the formation of joints in the
      adjacent digits. These data suggest that the role of GDF-5 in joint formation is
      the control of growth and differentiation of the cartilage of the epiphyseal
      regions of the phalanges rather than accounting for the differentiation of the
      sinovial joint tissues. The interdigital mesoderm in spite of its potential to
      form ectopic digits with their tendinous apparatus failed to form either ectopic
      cartilages or ectopic tendons after the implantation of GDF-5 beads in the stages
      preceding cell death. At difference with other BMPs, GDF-5 exhibited only a weak
      cell death promoting effect. The BMP antagonist Noggin binds to GDF-5 and is able
      to inhibit all the observed effects of this growth factor in vivo. Potential
      interactions of GDF-5 with other signals involved in digits morphogenesis were
      also explored. BMP-7 regulates negatively the expression of gdf-5 gene in the
      joint forming regions and local treatment with Noggin induces the ectopic
      expression of gdf-5 in the interdigital mesoderm. Retroviral-induced
      misexpression of Indian or Sonic Hedgehog genes in the developing digits leads to
      the formation of digits without joints in which gdf-5 expression occurs
      throughout the entire perichondrial surface. In conclusion, this study indicates
      that GDF-5 is a signal regulated by other BMPs which controls the growth and
      differentiation of the epiphyses of the digital cartilages acting in close
      relationship with Hedgehog signaling.

PMID- 9918694
TI  - AP-2alpha transcription factor is required for early morphogenesis of the lens
      vesicle.
AB  - AP-2 transcription factors are a family of retinoic acid-responsive genes, which
      are involved in complex morphogenetic processes. In the current study, we
      determine the requirement for AP-2alpha in early morphogenesis of the eye by
      examining the nature of the ocular defects in AP-2alpha null and chimeric mice.
      AP-2alpha null embryos exhibited ocular phenotypes ranging from a complete lack
      of eyes (anophthalmia) to defects in the developing lens involving a persistent
      adhesion of the lens to the overlying surface ectoderm. Two genes involved in
      lens development and differentiation, Pax6 and MIP26 were also misexpressed. AP
      2alpha mutants also exhibited defects in the optic cup consisting of
      transdifferentiation of the dorsal retinal pigmented epithelium into neural
      retina and the absence of a defined ganglion cell layer. Newly generated chimeric
      embryos consisting of a population of AP-2alpha-/- and AP-2alpha+/+ cells exhibit
      ocular defects similar to those seen in the knockout embryos. Immunolocalization
      of AP-2 proteins (alpha, beta, and gamma) to the normal developing eye revealed
      both unique and overlapping expression patterns, with AP-2alpha expressed in a
      number of the ocular tissues that exhibited defects in the mutants, including the
      developing lens where AP-2alpha is uniquely expressed. Together these findings
      demonstrate a requirement for AP-2alpha in early morphogenesis of the eye.

PMID- 9918695
TI  - Regulation of BMP signaling by the BMP1/TLD-related metalloprotease, SpAN.
AB  - We have used the Xenopus embryo as a test system for analyzing the activity of
      SpAN, a sea urchin metalloprotease in the astacin family containing BMP1 and
      tolloid. Embryos expressing SpAN initiated gastrulation on a time scale
      indistinguishable from controls, but invagination of the vegetal pole was
      subsequently delayed by several hours. At tailbud stages the most severely
      affected embryos were completely ventralized, lacking all dorsal structures.
      Molecular analysis of injected embryos, using probes for both dorsal (xgsc and
      xnot) and ventral (xhox3 and xwnt8) mesoderm, indicates that SpAN ventralizes
      dorsal mesoderm during gastrula stages. These results mirror those previously
      obtained with BMP4, suggesting that SpAN may enhance the activity of this
      ventralizing factor. Consistent with this suggestion, we have shown that SpAN
      blocks the dorsalizing activity of noggin and chordin, two inhibitory binding
      proteins for BMP4, but not that of a dominant-negative receptor for BMP4. In
      contrast, a dominant-negative SpAN, in which the metalloprotease domain has been
      deleted, dorsalizes ventral mesoderm, a phenotype that can be rescued by
      coexpressing either SpAN or XBMP1. This suggests that SpAN is mimicking a Xenopus
      metalloprotease responsible for regulating the activity of Xenopus BMPs during
      gastrulation. Moreover, our results raise the possibility that SpAN may function
      to facilitate BMP signaling in early sea urchin embryos.

PMID- 9918696
TI  - Expression of vasa(vas)-related genes in germline cells and totipotent somatic
      stem cells of planarians.
AB  - Planarians are known for their strong regenerative ability. This ability has been
      considered to reside in the totipotent somatic stem cell called the "neoblast."
      Neoblasts contain a unique cytoplasmic structure called the "chromatoid body,"
      which has similar characteristics to the germline granules of germline cells of
      other animals. The chromatoid bodies decrease in number and size during
      cytodifferentiation and disappear in completely differentiated cells during
      regeneration. However, germ cells maintain the chromatoid body during their
      differentiation from neoblasts. These observations suggest that the chromatoid
      body is concerned with the totipotency of cells. To understand the molecular
      nature of the chromatoid body in the neoblast, we focused on vasa (vas)-related
      genes, since VAS and VAS-related proteins are known to be components of the
      germline granules in Drosophila and Caenorhabditis elegans. By PCR, two vas
      related genes (Dugesia japonica vasa-like gene, DjvlgA and DjvlgB) were isolated,
      and they were shown to be expressed in germ cells. Interestingly, DjvlgA was also
      expressed in a number of somatic cells in the mesenchymal space. In regenerating
      planarians, accumulation of DjvlgA-expressing cells was observed in both the
      blastema and the blastema-proximal region. In X-ray-irradiated planarians, which
      had lost regenerative capacity, the number of DjvlgA-expressing cells decreased
      drastically. These results suggest that the product of DjvlgA may be a component
      of the chromatoid body and may be involved in the totipotency of the neoblast.

PMID- 9918697
TI  - Human mammary luminal epithelial cells contain progenitors to myoepithelial
      cells.
AB  - The origin of the epithelial and myoepithelial cells in the human breast has not
      been delineated. In this study we have addressed whether luminal epithelial cells
      and myoepithelial cells are vertically connected, i.e., whether one is the
      precursor for the other. We used a primary culture assay allowing preservation of
      basic phenotypic traits of luminal epithelial and myoepithelial cells in culture.
      The two cell types were then separated immunomagnetically using antibodies
      directed against lineage-specific cell surface antigens into at best 100% purity.
      The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D
      gel electrophoresis. Luminal epithelial cells were identified by strong
      expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by
      expression of vimentin and alpha-smooth muscle actin. We used a previously
      devised culture medium (CDM4) that allows vigorous expansion of proliferative
      myoepithelial cells and also devised a medium (CDM6) that allowed sufficient
      expansion of differentiated luminal epithelial cells based on addition of
      hepatocyte growth factor/scatter factor. The two different culture media
      supported each lineage for at least five passages without signs of
      interconversion. We used parallel cultures where we switched culture media, thus
      testing the ability of each lineage to convert to the other. Whereas the
      myoepithelial lineage showed no signs of interconversion, a subset of luminal
      epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We
      propose that in the mature human breast, it is the luminal epithelial cell
      compartment that gives rise to myoepithelial cells rather than the other way
      around.

PMID- 9918698
TI  - Genetic analysis of tissue interactions required for otic placode induction in
      the zebrafish.
AB  - Development of the vertebrate inner ear begins during gastrulation with induction
      of the otic placode. Several embryonic tissues, including cephalic mesendoderm,
      notochord, and hindbrain, have been implicated as potential sources of otic
      inducing signals. However, the relative contributions of these tissues have not
      been determined, nor have any genes affecting placode induction been identified.
      To address these issues, we analyzed otic placode induction in zebrafish mutants
      that are deficient in prospective otic-inducing tissues. Otic development was
      monitored by examining mutant embryos for morphological changes and, in some
      cases, by visualizing expression patterns of dlx-3 or pax-2.1 in preotic cells
      several hours before otic placode formation. In cyclops (cyc-) mutants, which
      develop with a partial deficiency of prechordal mesendoderm, otic induction is
      delayed by up to 1 h. In one-eyed pinhead (oep-) mutants, which are more
      completely deficient in prechordal mesendoderm, otic induction is delayed by 1.5
      h, and morphology of the otic vesicles is abnormal. Expression of marker genes in
      other regions of the neural plate is normal, suggesting that ablation of
      prechordal mesendoderm selectively inhibits otic induction. In contrast, the
      timing and morphology of otic development is not affected by mutations in no tail
      (ntl) or floating head (flh), which prevent notochord differentiation. Similarly,
      a mutation in valentino (val), which blocks early differentiation of rhombomeres
      5 and 6 in the hindbrain, does not delay otic induction, although subsequent
      patterning of the otic vesicle is impaired. To test whether inductive signals
      from one tissue can compensate for loss of another, we generated double or triple
      mutants with various combinations of the above mutations. In none of the multiple
      mutants do the flh or val mutations exacerbate delays in placode induction,
      although val does contribute additively to defects in subsequent patterning of
      the otic vesicle. In contrast, mutants homozygous for both oep and ntl, which
      interact synergistically to disrupt differentiation of cephalic and axial
      mesendoderm, show a delay in otic development of about 3 h. These data suggest
      that cephalic mesendoderm, including prechordal mesendoderm and anterior paraxial
      mesendoderm, provides the first otic-inducing signals during gastrulation,
      whereas chordamesoderm plays no discernible role in this process. Because val-
      mutants are deficient for only a portion of the hindbrain, we cannot rule out a
      role for that tissue in otic placode induction. However, if the hindbrain does
      provide otic-inducing signals, they apparently differ quantitatively or
      qualitatively from the signals required for vesicle patterning, as val disrupts
      only the latter.

PMID- 9918699
TI  - The lipid peroxidation product 4-hydroxynonenal impairs glutamate and glucose
      transport and choline acetyltransferase activity in NSC-19 motor neuron cells.
AB  - Both oxidative stress and excitotoxicity are implicated in the pathogenesis of a
      number of neurodegenerative disorders, such as amyotrophic lateral sclerosis. We
      previously reported increased modification of proteins by 4-hydroxynonenal (HNE),
      a product of membrane lipid peroxidation, in the spinal cords of patients with
      amyotrophic lateral sclerosis relative to controls. In the current study, we
      examined the functional consequences of protein modification by HNE in a cell
      line with a motor neuron phenotype, NSC-19. Treatment of NSC-19 cells with FeSO4,
      which catalyzes lipid peroxidation, or HNE induced concentration-dependent
      decreases in glucose and glutamate transport. Vitamin E and propyl gallate
      blocked the impairment of glucose and glutamate transport caused by FeSO4 in
      these cells, but not that caused by HNE, whereas glutathione blocked the effects
      of FeSO4 as well as HNE. Both FeSO4 and HNE caused an increase in the number of
      apoptotic nuclei in NSC-19 cultures, but this occurred subsequent to the
      impairment of glucose and glutamate transport. Reductions in choline
      acetyltransferase activity were also observed in FeSO4- or HNE-treated NSC-19
      cells before induction of apoptosis. Our results suggest that, prior to cell
      death, oxidative stress and HNE down-regulate cholinergic markers and impair
      glucose and glutamate transport in motor neurons, the latter of which may lead to
      excitotoxic degeneration of the cells.

PMID- 9918700
TI  - The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates tau
      mRNA expression and excitotoxicity.
AB  - As in Alzheimer's disease, brains of Guam Chamorros with amyotrophic lateral
      sclerosis (ALS) and Parkinsonism-dementia complex (PDC) contain intraneuronal
      paired helical filaments composed of accumulated phosphorylated tau protein. Tau
      mRNA expression in rat neuronal cultures-normally modulated by glutamate
      increases after treatment with the aglycone of cycasin, a cycad-derived toxin
      whose concentration in Chamorro food varies with disease incidence. Elevated Tau
      gene expression in vitro is coincident with increased cycasin-related DNA adducts
      and reduced DNA repair. Cycasin and endogenous glutamate may together promote the
      accumulation of tau protein and neuronal degeneration in Western Pacific ALS/PDC.

PMID- 9918701
TI  - Successful myoblast transplantation in primates depends on appropriate cell
      delivery and induction of regeneration in the host muscle.
AB  - Myoblast transplantation (MT) may be a potential treatment for severe recessive
      hereditary myopathies. The limited results of MT in clinical trials led us to
      improve this technique in monkeys, an animal model phylogenetically similar to
      humans. Three Macaca mulata monkeys were used as donors and six as receivers for
      MT. Myoblasts were grown in culture from muscle biopsies of adult monkeys and
      infected with a retroviral vector encoding the LacZ gene. Different numbers of
      cells (i.e., 4 x 10(6), 8 x 10(6), and 24 x 10(6) cells) were transplanted into
      different muscles and 8 x 10(6) cells (resuspended in a notexin solution) were
      injected in one muscle of four monkeys. For these transplantations, the cell
      suspension (in a volume of about 100 microl) was injected at 35 sites less than 1
      mm apart. Two other monkeys received 100 x 10(6) myoblasts resuspended in 1 ml of
      HBSS or 1 ml of notexin. For these two monkeys, the myoblasts were injected at
      200-250 sites within a small portion of the muscle. All monkeys were
      immunosuppressed with daily injections of FK506. Four weeks after MT, the
      transplanted muscle portions were biopsied and the presence of beta-galactosidase
      positive (beta-Gal+) muscle fibers was investigated. The number of beta-Gal+
      fibers was 822 +/- 150 (site grafted with 4 x 10(6) cells), 1253 +/- 515 (8 x
      10(6) cells), 1084 +/- 278 (24 x 10(6)), and 2852 +/- 1211 (notexin). In the
      monkeys grafted with 100 x 10(6) myoblasts, the number of beta-Gal+ fibers was
      4850 (site without notexin) and 9600 (site with notexin). We demonstrated that a
      precise mechanical distribution of myoblasts into the tissue improves
      substantially MT in primates. The presence of notexin with the transplanted cells
      further increased the success of their transplantation. These are the best
      results obtained either with MT or gene therapy in primates and they encourage
      the possibility to human MT trials.

PMID- 9918702
TI  - Myeloperoxidase polymorphism is associated with gender specific risk for
      Alzheimer's disease.
AB  - Myeloperoxidase (MPO) is a myeloid-specific enzyme that generates hypochlorous
      acid and other reactive oxygen species. MPO is present at high levels in
      circulating neutrophils and monocytes but is not detectable in microglia, brain
      specific macrophages, in normal brain tissue. However, an earlier study indicated
      that MPO is present in macrophage-microglia at multiple sclerosis lesions,
      suggesting that reactivation of MPO gene expression may play a role in
      neurodegenerative diseases involving macrophage-microglia. In the present study,
      MPO is shown to colocalize with amyloid beta (Abeta) in senile plaques in
      cerebral cortex sections from Alzheimer's disease (AD) brain tissue. Microglia
      costaining for MPO and CD68 are closely associated with plaques, suggesting that
      plaque components induce MPO expression in microglia. In support of this
      interpretation, treatment of rodent microglia with aggregated Abeta(1-42) was
      shown to induce MPO mRNA expression. Also, the ApoE4 allele, the major AD risk
      factor associated with increased Abeta deposition, was shown to correlate with
      increased MPO deposition in plaques (P = 0.01, ANOVA). Finally, a genetic
      polymorphism links MPO expression to Alzheimer's risk, in that a higher
      expressing SpSp MPO genotype was associated with increased incidence of AD in
      females, and decreased incidence in males (P = 0.006). These findings suggest
      that the MPO polymorphism is a gender-specific risk factor for Alzheimer's
      disease.

PMID- 9918703
TI  - Antiparkinsonian actions of blockade of NR2B-containing NMDA receptors in the
      reserpine-treated rat.
AB  - Current symptomatic treatment for Parkinson's disease is based largely on
      dopamine-replacing agents. The fact that long-term treatment with these drugs is
      characterized by many side effects has lead to widespread interest in
      nondopaminergic therapies. To date, however, it has proved difficult to devise a
      nondopaminergic therapy with significant antiparkinsonian efficacy when
      administered as monotherapy. Overactivity of the striatolateral pallidal pathway,
      the "indirect" striatal output pathway, is thought be responsible for the
      generation of parkinsonian symptoms. Indeed, it has been suggested that selective
      reduction in the activity of the "indirect" pathway may be achieved by blockade
      of NR2B-containing NMDA receptors. In the present study, we demonstrate that
      selective blockade of NR2B-containing NMDA receptors with the polyamine
      antagonists ifenprodil and eliprodil causes a significant increase in locomotor
      activity in the reserpine-treated rat model of Parkinson's disease (30 mg/kg
      ifenprodil, 221.2 +/- 54 mobile counts compared to vehicle, 19.6 +/- 6.87, P <
      0.001). Additionally, we show that, subsequent to dopamine depletion, the ability
      of ifenprodil to bind to the polyamine site and inhibit binding of the NMDA
      channel blocker [3H] MK-801 is increased fourfold (IC50 3.7 +/- 0.4 microM
      compared to vehicle, IC50 14.3 +/- 2.34 microM, P < 0.01). We suggest that
      ifenprodil selectively targets the polyamine site on overactive NR2B-containing
      NMDA receptors. Thus, we propose that NR2B-selective NMDA receptor antagonists
      may prove useful in the treatment of Parkinson's disease.

PMID- 9918704
TI  - Onset and progression of motor deficits in motor neuron degeneration (mnd) mice
      are unaltered by the glycine/NMDA receptor antagonist L-701,324 or the MAO-B
      inhibitor R(-)-deprenyl.
AB  - NMDA-mediated neurotoxicity and oxidative stress have been implicated in the
      etiology of a number of degenerative diseases including motor neuron disease. The
      present study examined the effect of chronic administration of the glycine/NMDA
      receptor antagonist L-701,324 and the monoamine oxidase B inhibitor (r)-deprenyl
      on the onset and rate of progression of neurological impairment in the motor
      neuron degeneration (mnd) mouse, a murine model of neurodegeneration.
      Neurological assessment of mnd mice revealed an onset of motor deficits at 6
      months of age as observed by the loss of hindlimb reflex extension. By 7 months,
      balance was also markedly impaired as measured by deficits in rotarod performance
      and ability to remain on balancing beams. At 8 months of age mnd mice exhibited
      gross abnormalities in walking pattern; animals were unable to flex their
      hindlimbs and tended to walk in small labored movements. Daily administration of
      L-701,324 (10 mg/kg p.o.) or r(-)-deprenyl (1 mg/kg p.o.) to mnd mice from 4 to 8
      months of age failed to delay the onset of symptoms or slow the rate of
      deterioration of motor performance. These findings suggest that excessive
      activation of NMDA receptors may not be involved in the pathological process
      leading to motor neuron dysfunction in mnd mice and do not suggest a protective
      effect of deprenyl on motor neurons in these mice.

PMID- 9918705
TI  - Nerve growth factor expressed in the medial septum following in vivo gene
      delivery using a recombinant adeno-associated viral vector protects cholinergic
      neurons from fimbria-fornix lesion-induced degeneration.
AB  - Nerve growth factor (NGF) has been shown to support the survival of axotomized
      medial septal cholinergic neurons after aspirative lesions of the fimbria-fornix
      (FF). This survival effect has been achieved utilizing intraventricular and
      intraparenchymal delivery of the NGF protein. While the use of NGF for the
      treatment of the cholinergic deficits present in Alzheimer's disease shows
      promise based on its efficacy in animal models, concerns about side-effects of
      intraventricular NGF delivery in humans have been raised. In the present study,
      NGF was delivered directly to the medial septum via a recombinant adeno
      associated viral vector (rAAV) encoding the cDNA for human NGF prior to a FF
      lesion in rats. This rAAV-mediated NGF delivery was shown to significantly
      attenuate the medial septal cholinergic cell loss observed in animals receiving
      an equivalent injection of a control rAAV vector.

PMID- 9918706
TI  - Fetal spinal cord transplants and exogenous neurotrophic support enhance c-Jun
      expression in mature axotomized neurons after spinal cord injury.
AB  - The responses of the central (CNS) and peripheral (PNS) nervous system to axotomy
      differ in a number of ways; these differences can be observed in both the cell
      body responses to injury and in the extent of regeneration that occurs in each
      system. The cell body responses to injury in the PNS involves the upregulation of
      genes that are not upregulated following comparable injuries to CNS neurons. The
      expression of particular genes following injury may be essential for regeneration
      to occur. In the present study, we have evaluated the hypothesis that expression
      of the inducible transcription factor c-Jun is associated with regrowth of
      axotomized CNS neurons. In these experiments, we compared c-Jun expression in
      axotomized brainstem neurons after thoracic spinal cord hemisection alone (a
      condition in which no regrowth occurs) and in groups of animals where
      hemisections were combined with treatments such as transplants of fetal spinal
      cord tissue and/or application of neurotrophic factors to the lesion site. The
      latter conditions enhance the capacity of the CNS for regrowth. We have
      demonstrated that hemisections alone do not upregulate expression of c-Jun,
      indicating that this particular cell body response is not a direct result of
      axotomy. However, c-Jun expression is upregulated in animals that received
      application of transplants and neurotrophins. Because these interventions also
      promote sprouting and regrowth of CNS axons after spinal cord lesions, we suggest
      that transplants and exogenous neurotrophic factor application activate a cell
      body response consistent with a role for c-Jun in axonal growth.

PMID- 9918708
TI  - Sympathectomy decreases formalin-induced nociceptive responses independent of
      changes in peripheral blood flow.
AB  - The present experiments studied the effect of surgical sympathectomy on
      mechanical paw withdrawal thresholds and formalin-induced pain behaviors (FIPB)
      and tested if the effect of sympathectomy on FIPB is dependent on changes in
      peripheral blood flow. Compared to sham-operated animals, surgical sympathectomy
      decreased second phase FIPB but did not affect paw withdrawal thresholds to
      mechanical stimuli. In sympathectomized and sham-operated animals, subcutaneous
      intraplantar injection of the nonadrenergic vasoconstrictor angiotensin II (20
      microl, 1 mM) or the nonadrenergic vasodilator hydralazine (20 microl, 1 mM)
      prior to formalin injection decreased and increased peripheral blood flow,
      respectively. In sympathectomized animals, pretreatment with angiotensin II
      inhibited the increase of peripheral blood flow following formalin injection when
      compared to animals pretreated with saline or hydralazine. In sham-operated
      animals, pretreatment with hydralazine or angiotensin II did not alter
      vasodilation after formalin injection when compared to pretreatment with saline.
      Pretreatment with vasoactive drugs had no effect on the sympathectomy-induced
      decrease in FIPB. It is concluded that sympathectomy decreases FIPB by mechanisms
      that are independent of sympathectomy-induced changes in peripheral blood flow.
      The formalin test is an easy, reliable model that can be used to study the
      mechanisms by which the sympathetic nervous system modulates pain processing.

PMID- 9918707
TI  - Metabotropic glutamate receptors prevent programmed cell death through the
      modulation of neuronal endonuclease activity and intracellular pH.
AB  - Metabotropic glutamate receptor (mGluR) activation prevents neurodegeneration
      against nitric oxide (NO)-induced programmed cell death (PCD). We therefore
      investigated whether specific neuronal endogenous deoxyribonucleases, enzymes
      recently identified to be responsible for the maintenance of DNA integrity,
      mediated mGluR protection against NO. In rat primary hippocampal neurons, injury
      was assessed by using a 0.4% trypan blue dye exclusion method and TUNEL assay 24
      h following treatment with the NO generators sodium nitroprusside (300 microM) or
      SIN-1 (300 microM). DNA digestion studies using neuronal cell extracts were
      employed to assess specific endonuclease activity. Individual application of
      aurintricarboxylic acid (ATA) (10 microM), an endonuclease inhibitor, or the
      mGluR agonists 1S,3R-ACPD (750 microM), DHPG (750 microM), L-CCG-I (750 microM),
      or L-AP4 (750 microM) prior to NO exposure significantly increased neuronal
      survival. Yet, combination therapy with ATA (10 microM) and the mGluR agonists
      did not synergistically improve neuronal survival, suggesting a common pathway of
      protection for ATA and the mGluRs that is dependent upon the modulation of
      neuronal endonuclease activity. In further support of this premise, protection by
      the mGluR agonists 1S,3R-ACPD, DHPG, L-CCG-I, and L-AP4 was significantly
      decreased during enhancement of endonuclease activity with the zinc chelator,
      N,N,N',N',-tetrakis (2-pyridylmethyl) ethylenediamine. Antagonism of the mGluR
      system was ineffective against endonuclease induced DNA destruction. Further
      assessment with DNA digestion assays identified two distinct mechanisms to
      maintain DNA integrity, a Ca2+/Mg2+-dependent endonuclease inhibited by L-AP4 and
      a magnesium dependent endonuclease inhibited by 1S,3R-ACPD. These neuroprotective
      mechanisms during activation of the mGluR system were also intricately linked to
      the active reversal of the biphasic intracellular pH changes induced by NO.
      Further investigation into the molecular pathways modulated by mGluRs may
      identify specific mechanisms that can maintain DNA integrity during adverse
      cellular environments.

PMID- 9918709
TI  - Inhibition of iron-dependent and ischemia-induced brain damage by the alpha
      tocopherol analogue MDL 74,722.
AB  - Free radical-induced lipid peroxidation is an important factor in the
      pathogenesis of ischemic brain damage. We studied the effects of the alpha
      tocopherol analogue MDL 74,722 on iron-dependent lipid peroxidation and infarct
      volume after transient focal cerebral ischemia. The effects of MDL 74,722 on iron
      induced lipid peroxidation were tested in cerebellar granule cell cultures by
      means of a thiobarbituric acid reactive substances (TBARS) assay. The absorbance
      resulting from mitochondrial reduction of 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) was taken as a measure of cell viability.
      Besides, in male Wistar rats the left middle cerebral artery (MCA) was occluded
      for 3 h by means of an intraluminal filament. Rats were treated with vehicle (n =
      19) or MDL 74,722 (n = 17), administered intravenously for 3 h in a dose of 2
      mg/(kg.h), starting 105 min after MCA occlusion. Infarct volume was measured in
      coronal brain sections stained with hematoxylin and eosin. In cerebellar granule
      cell cultures, MDL 74,722 resulted in a dose-dependent inhibition of TBARS
      formation and prevention of cell toxicity. The compound reduced infarct volume
      after transient occlusion of the MCA in rats by 49%. It is concluded that MDL
      74,722 is a potent inhibitor of lipid peroxidation and reduces infarct volume by
      about one half, even when treatment is delayed. This contributes to its potential
      clinical usefulness.

PMID- 9918710
TI  - Evidence that oxidative stress is associated with the pathophysiology of
      inherited hydrocephalus in the H-Tx rat model.
AB  - Oxidative stress can contribute to many neurological disease processes. Because
      many events known to involve oxidative stress (infection, hemorrhage, brain
      trauma) are accompanied by hydrocephalus, the present study sought to evaluate
      the relationship between oxidative stress and the progression of hydrocephalus.
      Assays for reactive oxygen species (ROS), using dichlorofluorescein (DCF)
      fluorescence, and lipid peroxidation, using malondialdehyde (MDA), were performed
      on brain tissue from the cerebral cortex, cerebellum, basal ganglia, and
      hippocampus of 4-, 10-, and 25-day-old normal and hydrocephalic H-Tx rats. These
      rats inherit hydrocephalus at a rate of 30-50% and represent a unique model for
      studying the progression of hydrocephalus. When hydrocephalic and normal H-Tx
      rats were compared, ROS levels were significantly higher in the cerebral cortex
      of 4-day-old and in the cerebellum and hippocampus of 4- and 10-day-old
      hydrocephalic rats. ROS levels also were significantly higher in the basal
      ganglia of 25-day-old hydrocephalic rats. MDA levels were significantly higher in
      the hippocampus and basal ganglia of 25-day-old hydrocephalic rats. There were no
      significant differences in MDA levels at younger ages. These results indicate
      that, in H-Tx rats, oxidative stress is associated with the progression and
      molecular pathophysiology of hydrocephalus. This association suggests that
      oxidative brain damage may represent an important factor resulting from or
      contributing to the pathogenesis of hydrocephalus.

PMID- 9918711
TI  - Differential sensitivity of cultured tanycytes and astrocytes to hydrogen
      peroxide toxicity.
AB  - Tanycytes present in the mediobasal hypothalamus are able to support axonal
      regeneration and neuron survival. Pilot experiments of transplantation of these
      cells into various lesioned areas of the central nervous system (CNS) were thus
      performed to determine whether these cells could support the regeneration of the
      lesioned axons. These pilot experiments, however, demonstrated that the grafted
      tanycytes failed to survive in the lesioned sites. The present study was designed
      to determine which of the compounds released at the lesion would be toxic for
      tanycytes. Tanycyte cultures obtained from the median eminence of 10-day-old rats
      and astrocyte cultures obtained from the cortex of 10-day-old rats or E-14
      embryos were incubated with two types of toxic molecules, including excitatory
      amino acids (EAA) and hydrogen peroxide (H2O2). The effect of these substances on
      cell death was estimated by measuring the lactate deshydrogenase (LDH) released
      and the surface occupied by immunostained glial structures after each treatment.
      The results indicated that the viability of both the tanycytes and the astrocytes
      was not affected by incubation for 24 h with 1 mM glutamate or 1 mM kainate. In
      contrast, increasing concentrations of H2O2 induced concentration-dependent cell
      death of tanycytes and immature astrocytes, without affecting the mature
      astrocytes. The use of antioxidant molecules such as catalase, tempol, or vitamin
      C effectively protected cultured tanycytes from H2O2 toxicity. These data
      indicate that (1) both mature astrocytes and tanycytes are resistant to EAA and
      (2) contrary to mature astrocytes, immature astrocytes and tanycytes are
      sensitive to the free radicals generated by H2O2. This suggest that oxidative
      stress is at least partly responsible for the death of tanycytes grafted into the
      lesioned CNS.

PMID- 9918712
TI  - Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult
      mouse optic fibers in vitro.
AB  - This study asks if there might be irreversible maturational changes in adult
      neurons that limit their capacity to regenerate. Retina from adult and embryonic
      mouse were placed in culture on laminin substrates so that regenerating adult
      optic fibers could be compared to growing embryonic fibers. Several cell adhesion
      molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes
      were assayed by immunocytochemistry: L1, N-cadherin, and NCAM. Thy 1.2, a
      potential CAM with inhibitory activity, was also examined. As in vivo, embryonic
      fibers were found to express both L1 and N-cadherin. In contrast, regenerating
      adult fibers had no detectable amounts of either of these CAMs. N-Cadherin is
      normally down regulated during development so its absence in adult fibers
      suggests it can not be reexpressed during regeneration. L1 is normally found in
      the proximal regions of adult optic fibers so its absence indicates it is not
      expressed or transported in regenerating fibers. Adult regenerating fibers
      expressed high levels of Thy 1.2, which was undetectable in embryonic optic
      fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic
      feature is preserved during regeneration. Both adult and embryonic fibers showed
      strong reactivity for NCAM, which in vivo is normally found in embryonic and at
      lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult
      fibers expressed high levels of polysialic acid, which is normally absent in
      adult fibers. NCAM may be one of few CAMs available to adult optic fibers for
      regeneration on astrocytes.

PMID- 9918713
TI  - MPTP-Induced pallidal lesions in rhesus monkeys.
AB  - Dopamine neurons in the substantia nigra of the midbrain are the primary neuronal
      population affected by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)
      toxicity, which produces the pathological and behavioral features of Parkinson's
      disease in nonhuman primates and man. We have identified another injury site in
      magnetic resonance imaging (MRI) brain scans in 13 of 37 rhesus monkeys taken 10
      12 months after administration of this neurotoxin via the right carotid artery.
      Focal lesions, ranging in volume from 6.75 to 60 mm3 in the rostral globus
      pallidus region, were seen on the right side of the brain in these 13 animals in
      addition to the midbrain effects. While no significant differences were seen
      between globus pallidus lesioned and nonlesioned animals in the severity of MPTP
      induced parkinsonian symptoms, the response to levodopa was muted in pallidal
      lesioned animals. To confirm the role of neurotoxicity in producing the lesions,
      brain scans from an additional 12 monkeys were evaluated during the acute period
      following exposure to either MPTP (n = 6) or saline (n = 6). Focal lesions in the
      rostral globus pallidus were seen as early as 2-4 h following a carotid artery
      infusion in two of six MPTP recipients, but no evidence of injury was seen in
      saline recipients. The globus pallidus includes important components of the
      neural circuitry regulating motor functions. The present results indicate that in
      addition to midbrain dopamine neurons, a focal region of the rostral globus
      pallidus is selectively vulnerable to MPTP toxicity.

PMID- 9918714
TI  - Hippocampal neurochemical and electrophysiological measures from freely moving
      rats.
AB  - This paper describes surgical and recording procedures that have been developed
      which permit the simultaneous monitoring of levels of select neurochemicals (via
      microdialysis) and measures of dentate-evoked field potentials within the
      hippocampal formation of freely moving adult rats. To test and evaluate these
      procedures, they were employed to examine changes in hippocampal neurochemistry
      and neuronal excitability associated with the establishment and maintenance of
      hippocampal long-term potentiation (LTP). Measures of hippocampal norepinephrine
      (NE) and glutamate levels along with measures of the dentate granule cell
      population spike amplitude (PSA) were obtained before, during, and after
      tetanization of the medial perforant path using two separate tetanization
      paradigms. Results obtained using these new procedures in several animals
      indicated that changes in NE and glutamate levels were strongly correlated with
      increases in the dentate granule cell PSA measure obtained following
      tetanization. The results indicate that this newly developed procedure can be
      effectively used to directly examine the relationship between neurochemical and
      neurophysiological changes associated with hippocampal neuroplasticity.

PMID- 9918716
TI  - The kinetics of sigma subunit directed promoter recognition by E. coli RNA
      polymerase.
AB  - Time-resolved laser UV irradiation and controlled proteolysis have been used to
      study the sequential recognition of the lac UV5 promoter by Escherichia coli RNA
      polymerase. Local rearrangements in the DNA, the appearance of intimate protein
      DNA contacts, and structural changes within the sigma subunit together provide
      specific signatures that define major species populated during this process. At
      22 degreesC, a first closed complex is characterised by a transient
      conformational change in the sigma subunit and by a distortion in the -35 region.
      Subsequently, direct contacts at -34 and at positions -8, -5 and -3 on the non
      template strand appear prior to DNA strand separation. The contact in the -35
      consensus region involves only the sigma subunit. This intermediate possesses
      different structural parameters from that formed by quenching open complexes from
      37 degreesC to 14 degreesC. Sigma thus appears as the principal partner acting
      during promoter recognition, a strongly coupled process involving two major
      intermediates only.

PMID- 9918715
TI  - The bacteriophage T4 transcriptional activator MotA accepts various base-pair
      changes within its binding sequence.
AB  - During infection, bacteriophage T4 regulates three sets of genes: early, middle,
      and late. The host RNA polymerase is capable of transcribing early genes, but
      middle transcription requires the T4-encoded transcriptional activator, MotA
      protein, and the T4 co-activator, AsiA protein, both of which bind to the sigma
      70 (sigma70) subunit of RNA polymerase. MotA also binds a DNA sequence (a MotA
      box), centered at position -30. The identification of more than 20 middle
      promoters suggested that a strong match to the MotA box consensus sequence
      (t/a)(t/a)TGCTT(t/c)A was critical for MotA activation. We have investigated how
      specific base changes within the MotA box sequence affect MotA binding and
      activation in vitro, and we have identified seven new middle promoters in vivo.
      We find that an excellent match to the sigma70 -10 consensus sequence, rather
      than an excellent match to the MotA box consensus sequence, is an invariant
      feature of MotA-dependent promoters. Many single base changes in the MotA box are
      tolerated in binding and activation assays, indicating that there is more
      flexibility in the sequence requirements for MotA than was previously
      appreciated. We also find that using the natural T4 DNA, which contains
      glucosylated, 5-hydoxymethylated cytosine residues, affects the ability of
      particular MotA box sequences to activate transcription. We suggest that MotA and
      AsiA may function like certain eukaryotic TAFs (TATA binding protein (TBP)
      associated factors) whose binding to TBP results in transcription from new core
      promoter sequences.

PMID- 9918717
TI  - The phenotype of mutations of G2655 in the sarcin/ricin domain of 23 S ribosomal
      RNA.
AB  - The sarcin/ricin domain (SRD) in Escherichia coli 23 S rRNA forms a part of the
      site for the association of the elongation factors with the ribosome and hence is
      critical for the binding of aminoacyl-tRNA and for translocation. The domain is
      also the site of action of the eponymous toxins which catalyze covalent
      modification of single nucleotides that inactivate the ribosome. The conformation
      of the conserved guanosine at position 2655 is an especially prominent feature of
      the structure of the SRD: the nucleotide is bulged out of a helix and forms a
      base-triple with A2665 and U2656. G2655 in 23 S rRNA is protected from chemical
      modification when the elongation factors, EF-Tu and EF-G, are bound to ribosomes
      and the analog of G2655 in oligoribonucleotides is critical for recognition by
      the toxin sarcin and by EF-G. The contribution of G2655 to the function of the
      ribosome has been evaluated by constructing mutations in the nucleotide and
      determining the phenotype. Constitutive expression of a plasmid-encoded rrnB
      operon with a deletion of, or transversions in, G2655 is lethal to E. coli cells,
      whereas a defect in the growth of cells with a G2655A transition is observed only
      in competition with wild-type cells. The sedimentation profiles of ribosomes with
      mutations in G2655 are altered; most markedly by deletion or transversion of the
      nucleotide, less severely by transition to adenosine. Mutations of G2655 confer
      resistance to sarcin on ribosomes. Ribosomes with G2655Delta, G2655C, or G2655U
      mutations in 23 S rRNA are not active in protein synthesis, whereas those with
      the G2655A transition mutation suffer decreased activity.

PMID- 9918718
TI  - Nucleosome dynamics. II. High flexibility of nucleosome entering and exiting DNAs
      to positive crossing. An ethidium bromide fluorescence study of mononucleosomes
      on DNA minicircles.
AB  - H2A-H2B exchange with the intranuclear histone pool upon chromatin transcription
      in vivo is generally viewed as being triggered by the DNA positive supercoiling
      wave pushed by the elongating polymerase. This notion was tested here by
      investigating a potential release of H2A-H2B by ethidium bromide-induced positive
      supercoiling in the loop of mononucleosomes reconstituted on DNA minicircles. The
      results of gel electrophoresis, fluorescence titration and electron microscopy
      showed that such a positive supercoiling was not able to release H2A-H2B, nor to
      unfold the nucleosome to any detectable extent. The reason appeared to be the
      ease with which the loop could undergo a positive crossing, a surprising
      observation in view of the DNA left-handed wrapping around the octamer. Moreover,
      the influence of histone acetylation suggested that such loop flexibility to
      positive crossing is mediated by histone N-terminal tails which, by interacting
      with entering and exiting DNAs, reduce their electrostatic repulsion. These
      conclusions are confirmed and extended in the accompanying article through
      relaxation with topoisomerase I.

PMID- 9918719
TI  - Nucleosome dynamics. III. Histone tail-dependent fluctuation of nucleosomes
      between open and closed DNA conformations. Implications for chromatin dynamics
      and the linking number paradox. A relaxation study of mononucleosomes on DNA
      minicircles.
AB  - The mean linking number (<Lk>) of the topoisomer equilibrium distribution
      obtained upon relaxation of DNA minicircles with topoisomerase I did not increase
      linearly, but rather in a step wise fashion, with DNA size between 351 and 366
      bp. As a consequence, the corresponding linking number difference (<DeltaLk>) did
      not remain equal to 0, but rather oscillated between +/-0.3 with the periodicity
      of the double helix. This oscillation, not observed with plasmid-size DNA, is an
      expected consequence of the stiffness of short DNA. When minicircles were
      reconstituted with a nucleosome, the associated <DeltaLkn> oscillated between
      approximately -1.4 +/-0. 2. This oscillation appears to result from the combined
      effects of DNA stiffness, and nucleosome ability to thermally fluctuate between
      three distinct DNA conformational states. Two of these states, a closed
      approximately 1.75-turn DNA conformation with negatively crossed entering and
      exiting DNAs, and an open approximately 1.4-turn conformation with uncrossed
      DNAs, are well known, whereas the third state, with a closed DNA conformation and
      DNAs tending to cross positively rather than negatively, is less familiar. Access
      to both closed "negative" and "positive" states appears to be mediated by histone
      N-terminal tails, as shown by specific alterations to the <DeltaLkn> oscillation
      caused by histone acetylation and phosphate ions, a potent tail destabilizator.
      These results extend previous observations of ethidium bromide fluorescence
      titration in the accompanying article, which have pointed to an histone tail
      dependent flexibility of entering and exiting DNAs to positive crossing. They
      also show that DNA wrapping around the histones occurred without twist alteration
      compared to the DNA free in solution, and reveal an intriguing new facet of the
      "linking-number-paradox" problem: the possibility for linkers in chromatin to
      adopt different crossing status within an overall dynamic equilibrium which may
      be regulated by histone acetylation.

PMID- 9918720
TI  - Mutational analysis of target base flipping by the EcoRV adenine-N6 DNA
      methyltransferase.
AB  - DNA methyltransferases flip their target base out of the DNA helix. Here, we have
      investigated base flipping by wild-type EcoRV DNA methyltransferase (M.EcoRV) and
      five M.EcoRV variants (D193A, Y196A, S229A, W231R and Y258A). These variants bind
      to DNA and S-adenosylmethionine but have a severely reduced catalytic efficiency
      or are catalytically inactive. To measure base flipping three different assays
      were used, viz. analysis of the yields of photocrosslinking reactions between the
      enzymes and a substrate in which the target base is replaced by 5-iodouracil,
      analysis of the binding constants to substrates containing a mismatch base-pair
      at the target position and analysis of the salt dependence of specific complex
      formation. Our data show that the Y196A, W231R and Y258A variants are not able to
      stabilize a flipped target base, suggesting that the aromatic amino acid residues
      (Tyr196, Trp231 and Tyr258) are involved in hydrophobic interactions with the
      flipped base. The D193A variant behaves like wild-type M.EcoRV with respect to
      base flipping. The fact that this variant is catalytically inactive indicates
      that Asp193 has a function in chemical catalysis. The S229A variant can better
      flip modified bases but does not tightly lock the flipped base into the adenine
      binding pocket, suggesting that Ser229 could form a contact to the flipped
      adenine.

PMID- 9918721
TI  - Association of holliday-structure resolving endonuclease VII with gp20 from the
      packaging machine of phage T4.
AB  - Endonuclease VII (endo VII) is the product of gene 49 (gp49) of bacteriophage T4.
      It is a Holliday-structure resolvase (X-solvase) responsible for clearing
      branched replicative DNA prior to packaging. Consequently, mutations in gene 49
      are unable to fill heads to completion because unresolved branches stop
      translocation of DNA. A likely association of gp49 with heads or proheads,
      however, could not be shown in the past. We have investigated whether gp49 could
      be part of the transiently assembled packaging machine (the "packasome") located
      at the base of proheads. Using purified proteins gpl6, gpl7 and gp20, which are
      constituents of the packasome, we found that gp49 binds tightly to gp20 and does
      not bind to gpl6 or gpl7. Quantification revealed that one dimer of gp49 binds
      one monomer of gp20. Notably, dimerisation of gp49 was an essential prerequisite
      for complex formation with gp20, and the dimerisation-deficient point mutation
      His-EVII-W87R showed only residual affinity to gp20. Furthermore, truncated
      peptides of gp49 deficient in dimer formation to various degrees were found to be
      impaired in binding to gp20. In contrast, the cleavage-deficient mutation EVII
      N62D bound normally to gp20. The cruciform DNA (cf-DNA) resolving activity
      typical of endo VII is maintained in gp20-gp49 complexes. Furthermore, the
      complexes bind cf-DNA in the absence of Mg2+ as demonstrated by electromobility
      shift assays. The binding of the complexes to cf-DNA occurs via gp49, since gp20
      alone does not bind cf-DNA. In conclusion, these findings are consistent with a
      model in which gp49 is an integral part of the packaging machine of phage T4.

PMID- 9918722
TI  - Refined crystal structures of native human angiogenin and two active site
      variants: implications for the unique functional properties of an enzyme involved
      in neovascularisation during tumour growth.
AB  - Human angiogenin (Ang), an unusual member of the pancreatic RNase superfamily, is
      a potent inducer of angiogenesis in vivo. Its ribonucleolytic activity is weak
      (10(4) to 10(6)-fold lower than that of bovine RNase A), but nonetheless seems to
      be essential for biological function. Ang has been implicated in the
      establishment of a wide range of human tumours and has therefore emerged as an
      important target for the design of new anti-cancer compounds. We report high
      resolution crystal structures for native Ang in two different forms (Pyr1 at 1.8
      A and Met-1 at 2.0 A resolution) and for two active-site variants, K40Q and H13A,
      at 2.0 A resolution. The native structures, together with earlier mutational and
      biochemical data, provide a basis for understanding the unique functional
      properties of this molecule. The major structural features that underlie the
      weakness of angiogenin's RNase activity include: (i) the obstruction of the
      pyrimidine-binding site by Gln117; (ii) the existence of a hydrogen bond between
      Thr44 and Thr80 that further suppresses the effectiveness of the pyrimidine site;
      (iii) the absence of a counterpart for the His119-Asp121 hydrogen bond that
      potentiates catalysis in RNase A (the corresponding aspartate in Ang, Asp116, has
      been recruited to stabilise the blockage of the pyrimidine site); and (iv) the
      absence of any precise structural counterparts for two important purine-binding
      residues of RNase A. Analysis of the native structures has revealed details of
      the cell-binding region and nuclear localisation signal of Ang that are critical
      for angiogenicity. The cell-binding site differs dramatically from the
      corresponding regions of RNase A and two other homologues, eosinophil-derived
      neurotoxin and onconase, all of which lack angiogenic activity. Determination of
      the structures of the catalytically inactive variants K40Q and H13A has now
      allowed a rigorous assessment of the relationship between the ribonucleolytic and
      biological activities of Ang. No significant change outside the enzymatic active
      site was observed in K40Q, establishing that the loss of angiogenic activity for
      this derivative is directly attributable to disruption of the catalytic
      apparatus. The H13A structure shows some changes beyond the ribonucleolytic site,
      but sites involved in cell-binding and nuclear translocation are essentially
      unaffected by the amino acid replacement.

PMID- 9918723
TI  - The crystal structure of the sevenfold mutant of barley beta-amylase with
      increased thermostability at 2.5 A resolution.
AB  - The three-dimensional structure of the sevenfold mutant of barley beta-amylase
      (BBA-7s) with increased thermostability was determined by X-ray crystallography.
      The enzyme was purified as a single component and crystallized by a hanging drop
      method in the presence of 14 % PEG 6000. The crystals belong to space group
      P43212 with cell dimensions a=b=72.11 A, c=250.51 A. The diffraction data up to
      2.5 A were collected after soaking the crystal in 100 mM maltose with Rsym of 8.6
      %. The structure was determined by a molecular replacement method using soybean
      beta-amylase (SBA) as a search model and refined to an R-factor of 18.7 %. The
      final model included 500 amino acid residues, 141 water molecules and three
      glucose residues, which were located at subsites 1-2 and 4 in the active site.
      The r.m.s. distance of 485 Calpha atoms between BBA-7s and SBA was 0.62 A. Out of
      the seven mutated amino acids, four (Ser295Ala, Ile297Val, Ser351Pro and
      Ala376Ser) were substitutions from the common residues with SBA to the
      thermostable forms. A comparison of the structures of BBA-7s and SBA indicated
      that the side-chain of Ser376 makes new hydrogen bonds to the main-chain of an
      adjacent beta-strand, and that the side-chains of Val297 reduce an unfavorable
      interaction between the side-chains of Ala314. The mutation of Ser295Ala breaks
      the hydrogen bond between Ser295 OG and Tyr195 OH, which seems to be the reason
      for the unoccupied glucose residue at subsite 3. The tandem mutations at 350-352
      including substitutions to two Pro residues suggested the reduction of main-chain
      entropy in the unfolded structure of this solvent-exposed protruded loop.

PMID- 9918724
TI  - Crystal structure of intact elongation factor EF-Tu from Escherichia coli in GDP
      conformation at 2.05 A resolution.
AB  - The crystal structure of intact elongation factor Tu (EF-Tu) from Escherichia
      coli in GDP-bound conformation has been determined using a combination of
      multiple isomorphous replacement (MIR) and multiwavelength anomalous diffraction
      (MAD) methods. The current atomic model has been refined to a crystallographic R
      factor of 20.3 % and free R-factor of 26.8 % in the resolution range of 10-2.05
      A. The protein consists of three domains: domain 1 has an alpha/beta structure;
      while domain 2 and domain 3 are beta-barrel structures. Although the global fold
      of the current model is similar to those of published structures, the secondary
      structural assignment has been improved due to the high quality of the current
      model. The switch I region (residues 40-62) is well ordered in this structure.
      Comparison with the structure of EF-Tu in GDP-bound form from Thermus aquaticus
      shows that although the individual domain structures are similar in these two
      structures, the orientation of domains changes significantly. Interactions
      between domains 1 and 3 in our E. coli EF-Tu-GDP complex are quite different from
      those of EF-Tu with bound GTP from T. aquaticus, due to the domain rearrangement
      upon GTP binding. The binding sites of the Mg2+ and guanine nucleotide are
      revealed in detail. Two water molecules that co-ordinate the Mg2+ have been
      identified to be well conserved in the GDP and GTP-bound forms of EF-Tu
      structures, as well as in the structure of Ras p21 with bound GDP. Comparisons of
      the Mg2+ binding site with other guanine nucleotide binding proteins in GDP-bound
      forms show that the Mg2+ co-ordination patterns are well preserved among these
      structures.

PMID- 9918725
TI  - MRI-Based topographic parcellation of human cerebral white matter.
AB  - We describe a virtually automatic comprehensive parcellation of the human
      cerebral central white matter, which is based upon T1-weighted MRI scans. The
      system, which is "rule-based," is developed from prior anatomic studies of the
      human brain and experimental studies of connectivity in animals as elaborated in
      the companion manuscript. Boundaries which delineate anatomic subregions of the
      white matter are computed from the geometric features of anatomic landmarks
      visible in the imaging data. The fiber systems of the central white matter are
      ordered topographically into three compartments, reflecting the inferred
      arrangements of principal neural systems pathways. These include an outer radiate
      (fibers principally radially aligned), an intermediate sagittal (fibers
      principally sagittally aligned), and deep bridging (fibers bridging hemispheres
      or cortex and deep structures) compartments. Each of these compartments is
      secondarily parcellated into smaller units to increase the anatomic specificity
      and spatial resolution of the system. The principal intended uses for this system
      of anatomic subdivision are for the volumetric characterization of forebrain
      white matter in normal and abnormal brains and for precision and specificity of
      localization in focal lesion-deficit correlation studies.

PMID- 9918726
TI  - MRI-Based topographic parcellation of human cerebral white matter and nuclei II.
      Rationale and applications with systematics of cerebral connectivity.
AB  - We describe a system for parcellation of the human cerebral white matter and
      nuclei, based upon magnetic resonance images. An algorithm for subdivision of the
      cerebral central white matter according to topographic criteria is developed in
      the companion manuscript. In the present paper we provide a rationale for this
      system of parcellation of the central white matter and we extend the system of
      cerebral parcellation to include principal subcortical gray structures such as
      the thalamus and the basal ganglia. The volumetric measures of the subcortical
      gray and white matter parcellation units in 20 young adult brains are computed
      and reported here as well. In addition, with the comprehensive system for
      cerebral gray and white matter structure parcellation as reference, we formulate
      a systematics of forebrain connectivity. The degree to which functionally
      specific brain areas correspond to topographically specific areas is an open
      empirical issue. The resolution of this issue requires the development of
      topographically specific anatomic analyses, such as presented in the current
      system, and the application of such systems to a comprehensive set of functional
      anatomic correlation studies in order to establish the degree of structural
      functional correspondence. This system is expected to be applied in both
      cognitive and clinical neuroscience as an MRI-based topographic systematics of
      human forebrain anatomy with normative volumetric reference and also as a system
      of reference for the anatomic organization of specific neural systems as
      disrupted by focal lesions in lesion-deficit correlations.

PMID- 9918727
TI  - Neuronal mechanisms of perceptual learning: changes in human brain activity with
      training in orientation discrimination.
AB  - Using 15O-water 3D positron emission tomography, regional cerebral blood flow was
      measured twice in six human subjects: before and after extensive training in
      orientation discrimination. In each session subjects performed two orientation
      discrimination tasks, during which they discriminated the orientation of a
      grating at either the trained or untrained reference orientation, and a control
      task, during which they detected a randomly textured pattern. By comparing the
      discrimination to the detection tasks, we observed a main effect of task
      bilaterally in the posterior occipital cortex, extending into the left posterior
      fusiform gyrus and the right inferior occipital gyrus, bilaterally in the
      intraparietal sulcus, as well as in the cerebellum, thalamus, and brainstem. When
      we compared the activation pattern before and after the training period, all the
      changes observed were activity decreases. The nonspecific changes, which were not
      related to the orientation used during the training, were situated in the
      cerebellum and bilaterally in the extrastriate visual cortex. The orientation
      specific changes, on the other hand, were restricted to the striate and
      extrastriate visual cortex, more precisely the right calcarine sulcus, the left
      lingual gyrus, the left middle occipital, and the right inferior occipital gyrus.
      These findings confirm our hypothesis concerning the existence of learning
      related changes at early levels of visual processing in human adults and suggest
      that mechanisms resulting in neuronal activity decreases might be involved in the
      present kind of learning.

PMID- 9918728
TI  - Rapid assessment of regional cerebral metabolic abnormalities in single subjects
      with quantitative and nonquantitative [18F]FDG PET: A clinical validation of
      statistical parametric mapping.
AB  - The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has
      not the wide clinical application that one might expect, partly because of its
      high cost and the complexity of the quantification procedure, but also because of
      reporting techniques based on region of interest (ROI) analysis, which are time
      consuming and not fully objective. In this paper we report a clinical validation
      of statistical parametric mapping (SPM) using rCMRglc (quantitative) and
      radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10
      min noninteractive voxel-based SPM analysis on a standard workstation enables
      objective assessment, including localization in stereotactic space, of regional
      glucose consumption abnormalities, whose reliability can be assessed on
      statistical and clinical grounds. Clinical validity was established using a small
      series of patients with degenerative or developmental disorders, including
      probable Alzheimer's disease, progressive aphasia, multiple sclerosis,
      developmental specific language impairment, and epilepsy. Analysis of
      quantitative and nonquantitative data showed the same pattern of results,
      suggesting that, for clinical purposes, quantitation and invasive arterial
      cannulation can be avoided. This should facilitate a wider application of the
      technique and the extension of SPM clinical analysis to H215O PET or high
      resolution SPECT perfusion studies.

PMID- 9918729
TI  - Motor dysfunction and sensorimotor cortex activation changes in schizophrenia: A
      study with functional magnetic resonance imaging.
AB  - Recent studies demonstrate a diminished activation of the sensorimotor cortex and
      supplementary motor area (SMA) in schizophrenia which may be involved in the
      pathogenesis of neurological soft signs (NSS). Yet, the question whether a
      retarded motor performance may account for these changes remained to be
      clarified. Twelve DSM-III-R schizophrenics and 12 healthy controls were included.
      All subjects were right-handed. Nine patients received clozapine, two
      conventional neuroleptics, and one was drug-free. Functional magnetic resonance
      imaging (fMRI) was obtained in a resting condition and during
      pronation/supination at three speed levels (low, medium, and high) with motor
      performance recorded simultaneously using a pronation/supination device. While
      measures of motor retardation (i.e., repetition rate and amplitude of the
      movements) did not differ between patients and controls, the variability of
      performance was significantly (P < 0.05) increased in the patients' group. In
      addition, patients with schizophrenia showed a significantly (P < 0.05) decreased
      activation of the sensorimotor cortices. Similar, although nonsignificant (P =
      0.09) activation changes were observed in the SMA. Activation differences were
      more pronounced at a slow speed and in the drug-free patient. These results
      confirm a diminished sensorimotor cortex and SMA activation and indicate that
      variability of performance rather than retarded performance per se may correspond
      to these changes.

PMID- 9918730
TI  - Functional neuroanatomy of semantic memory: recognition of semantic associations.
AB  - In an effort to examine the functional neuroanatomy of semantic memory, we
      studied the relative cerebral blood flow of eight healthy young subjects using
      15O-water positron emission tomography (PET). Relative to a visual baseline
      control condition, each of four visual matching-to-sample tasks activated
      components of the ventral visual processing stream, including the inferior
      occipital and temporal cortices. Contrasting the task with the highest semantic
      component, a variation on the Pyramids and Palm Trees paradigm, with a size
      discrimination task resulted in focal activation in the anterior inferior
      temporal lobe, focused in the parahippocampal gyrus. There was additional
      activation in BA47 of the inferior frontal cortex. These data replicate and
      extend previously reported results using similar paradigms, and are consistent
      with cognitive neuropsychological models that stress the executive role of BA47
      in semantic processing tasks.

PMID- 9918731
TI  - Activation of human extrageniculostriate pathways after damage to area V1.
AB  - We have used positron emission tomography (PET) to specify the cortical and
      subcortical structures activated following visual stimulation of the scotomatous
      field in a patient with an asymmetric bilateral developmental anomaly of the
      visual cortex. Computerized perimetry indicated a left visual field defect only
      although MRI and 18FDG-PET scans showed abnormalities in both occipital lobes.
      The visual stimuli were semicircular gratings moving in opposite directions on a
      dynamic random-dot background. They were specifically constructed to eliminate
      intra- and extraocular light scatter and to optimize the activation of extra
      striate cortical areas and their projecting subcortical relays. For anatomical
      localization PET images were coregistered to the subject's MRI in Talairach
      coordinates. After subtraction of the baseline conditions from the stimulation
      conditions, a t-statistic map was created on a voxel-by-voxel basis. Stimulation
      of the scotomatous hemifield yielded significant activations of Brodmann cortical
      areas 18-19 and 47 as well as the pulvinar thalami of the left hemisphere, in
      addition to a less prominent activation in the right hemisphere. Stimulation of
      the intact hemifield produced significant activation of Brodmann cortical areas
      30 and 47 of the left hemisphere. These results suggest that in the absence of
      area V1, residual vision observed in the blind hemifield could be mediated by a
      retinofugal pathway to extrastriate cortex via the pulvinar.

PMID- 9918732
TI  - Visualization of the dopamine transporter in the human brain postmortem with the
      new selective ligand [125I]PE2I.
AB  - Using a new, 125I-labeled, selective high affinity dopamine transporter ligand, N
      (3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methy lph enyl)nort ropane
      (PE2I), the distribution of the dopamine transporter was characterized in the
      normal postmortem human brain using whole hemisphere autoradiography. PE2I was
      radioiodinated to high specific radioactivity (2200 Ci/mmol, 81 GBq/micromol).
      PE2I binds to the dopamine transporter with high potency and, in contrast to beta
      CIT, it has very low affinities for the serotonin and noradrenaline transporters.
      The autoradiograms showed very intense binding in basal ganglia (putamen, nucleus
      caudatus, nucleus accumbens) and lower binding in substantia nigra. Very low or
      no binding was found in other brain structures, including the neocortex or
      cerebellum. The labeling of human dopamine transporters with [125I]PE2I was
      inhibited by the dopamine transporter inhibitors GBR 12909 and beta-CIT, but not
      by citalopram (serotonin transporter inhibitor) or maprotiline (noradrenaline
      transporter inhibitor). Possibly due to the relatively high lipophilicity of the
      compound (theoretical log p = 4.68), it accumulated slightly in white matter.
      Thus, in vitro autoradiography using [125I]PE2I provided detailed qualitative and
      quantitative evidence that the dopamine transporter is almost exclusively
      localized in the basal ganglia of the human brain. Moreover, the autoradiograms
      indicate that [11C]PE2I and [123I]PE2I should be suitable for the in vivo
      visualization of the human dopamine transporter with PET or SPECT, respectively.

PMID- 9918733
TI  - Subregions within the supplementary motor area activated at different stages of
      movement preparation and execution.
AB  - Previous studies have provided evidence that the primary motor area (M1) is
      involved in actual execution of a motor program, while the premotor area (PreMA)
      and the supplementary motor area (SMA) play a role in its preparation. We have
      used the high temporospatial resolution of functional magnetic resonance imaging
      (fMRI) to study the relationship between stages of a motor program and activation
      of these motor-related cortical areas. Seven normal volunteers performed a
      delayed-motor task in which the preparation of finger movements was dissociated
      in time from movement execution, while event-related fMRI was obtained. The M1
      and PreMA showed expected activation associated with execution and preparation
      stages, respectively. Within SMA, subregions with different temporal profiles of
      activation were identified: The anterior part became activated early in the
      preparation period, whereas the posterior part only with movement execution. This
      supports the notion that the classic SMA consists of the pre-SMA and SMA proper
      each with different functions.

PMID- 9918734
TI  - Neuroimage of voluntary movement: topography of the Bereitschaftspotential, a 64
      channel DC current source density study.
AB  - The Bereitschaftspotential (BP) was recorded at 56 scalp positions when 17
      healthy subjects performed brisk extensions of the right index finger. Aim of the
      study was to contribute to our understanding of the physiology underlying the BP
      and, in particular, to specify the situation at BP onset. For this purpose, the
      spatial pattern of the BP was analyzed in short time intervals (35 and/or 70 ms)
      starting 2.51 s before movement onset. For each time segment a spherical model of
      the BP was calculated by using spline interpolation. Then the spatial
      distribution of the electric potential at the scalp surface was transformed into
      a spatial distribution of current source densities (CSD map). Onset times of the
      BP and onset times of initial CSD-activity ranged between 2.23 and 1.81 s before
      movement onset. We selected a time window between 1.6 and 1.5 s before movement
      onset in order to analyze the spatial CSD pattern in each subject. In 10 subjects
      there was a significant current sink in the scalp area located over medial-wall
      motor areas (pre-SMA, SMA proper and anterior cingulate cortex: electrode
      positions C1, C2, FCz, Cz) in the absence of a significant current sink over the
      primary motor cortex (MI: electrode positions C3, CP3, and CP5). In three
      subjects significant current sinks were present at both sites and in another
      three subjects a current sink only over the lateral motor cortex was observed. In
      one subject no significant current sinks were measured. It is concluded that
      there is a large group of subjects (13/17) in whom BP at onset is associated with
      a current sink over medial-wall motor areas. At a later time interval (0.6 to 0.5
      s before movement onset), significant current sinks were found in 13 subjects in
      medial and in 10 subjects in lateral recordings. These data were considered to be
      consistent with the hypothesis that, at least in a majority of subjects, medial
      wall motor areas are activated earlier than lateral motor areas when organizing
      the initiation of a simple self-paced movement. Surface-recordings of the EEG do
      not allow further specification of cortical areas, which contribute to the
      current sinks. But in context with the current literature of the
      electrophysiology of nonhuman primates and of brain imaging in humans it is
      suggested that SMA and anterior cingulate cortex contribute to the current sink,
      the fronto-central midline, and that the primary motor cortex (MI) contributes to
      the current sink in the scalp area, which is located above MI and closely
      posterior to it.

PMID- 9918735
TI  - Differential fMRI responses in the left posterior superior temporal gyrus and
      left supramarginal gyrus to habituation and change detection in syllables and
      tones.
AB  - Using a habituation-recovery paradigm adapted to functional magnetic resonance
      imaging, we investigated the brain responses to syllables and tones in six right
      handed male subjects. We opposed a standard condition (STD) in which the subjects
      were listening to homogeneous sequences of four identical stimuli, to a deviant
      condition (DEV) in which the fourth stimulus of the sequence differed in pitch or
      spectral content for tones and in the initial stop consonant for syllables. The
      corresponding runs alternated four rest periods with two STD and two DEV
      conditions. In addition to a marked rightward asymmetry in the primary and
      secondary auditory cortex for tones and a right inferior frontal activation for
      the tone condition where the deviant had increased spectral content, the
      experiment revealed differential activations in the left posterior superior
      temporal gyrus and in the left supramarginal gyrus. Activations within the left
      posterior superior temporal gyrus were observed for the DEV condition with tones
      and for the STD and DEV conditions with syllables. Activation within the inferior
      part of the left supramarginal gyrus was only observed for the DEV condition with
      syllables. The analysis of the decreases and increases in the BOLD signal across
      the STD, DEV, and rest conditions suggests that the left posterior superior
      temporal gyrus is implicated in the preattentive change detection of acoustic
      changes in speech as well as nonspeech stimuli, whereas the left supramarginal
      gyrus is more specifically engaged in the detection of changes in phonological
      units.

PMID- 9918737
TI  - Verb generation in Japanese--A multicenter PET activation study.
AB  - Cerebral blood flow (CBF) during silent verb generation was measured at four
      Japanese PET centers. To minimize the variance of the measurement, speakers of a
      single language (Japanese) served as subjects and experimental conditions at the
      four PET centers were controlled as much as possible. Two types of activation
      patterns were observed: activations in the left dorsolateral prefrontal cortices
      and the medial frontal cortex (at the two centers with a 2D PET scanner) and
      additional activation in the left posterior temporal cortex (at the two centers
      with a 3D scanner). This suggests either a difference in the sensitivity of the
      two types of PET scanners (viz., a 3D scanner is generally more sensitive than a
      2D scanner) and/or subject bias due to the small number of subjects at the
      individual centers. The pooled activation pattern was fundamentally similar to
      activation patterns obtained in the previous studies for verb generation in
      English and other European languages, suggesting that regions for verb generation
      are independent of particular languages. Regions relevant to verb generation are
      discussed.

PMID- 9918738
TI  - Observer-independent method for microstructural parcellation of cerebral cortex:
      A quantitative approach to cytoarchitectonics.
AB  - We describe a new, observer-independent procedure for identifying boundaries
      between cortical areas. The method is useful for images obtained from sections
      which provide microstructural information on the cortical laminar pattern, e.g.,
      Nissl-, myelin-, or immunohistochemically stained sections or receptor
      autoradiographs. The laminar pattern is represented by profile curves extending
      from the cortical surface to the white matter boundary. These profiles are
      constructed from digitized images. Digitization is based on the grey level index
      (Nissl) or densitometry (myelin, immunohistochemistry, receptor autoradiography).
      The shapes of neighboring profiles are compared by calculating their distances
      according to feature vectors extracted from the profiles. Profiles derived from a
      homogeneous area can be expected to be similar in shape and hence show low
      distance values between each other. Maximum distances can be found between
      profiles which lie on opposite sides of a structural boundary. The Mahalanobis
      distance was found to be more sensitive and to yield greater spatial resolution
      than other distance measures such as the Euclidean distance. Cell-stained
      sections of the human neocortex were analyzed. The method not only verified
      boundaries which had been defined by visual inspection, it also revealed new ones
      which had not been detected visually. The procedure offers an important
      supplement to the traditional methods based on visual inspection which, for the
      first time, is based on quantitative data and therefore offers a new level of
      reproducibility and observer independence. Anatomical atlases based on this
      procedure thus provide a new tool for the interpretation of structural data
      obtained from functional imaging techniques.

PMID- 9918739
TI  - Preface 

PMID- 9918736
TI  - A study of injected dose for brain mapping on the ECAT HR+: activation maps for a
      parametric verbal working memory task.
AB  - The success of the 15O-water PET technique to localize statistically significant
      changes in regional cerebral blood flow is dependent on factors such as the
      activity level injected and the magnitude of the flow change. Undetectable
      changes may occur if insufficient activity is injected leading to high levels of
      statistical noise or the task performed results in only small changes in blood
      flow. To explore the relationship between injected activity and statistical
      significance, we performed a series of studies with the ECAT EXACT HR+, a high
      resolution PET tomograph. A parametric verbal working memory task (the N-back
      task) was selected to examine the relationship between regional cerebral blood
      flow and working memory load across a range of injected doses of 15O-water. At
      each activity level the volunteers were required to perform four different levels
      of the N-back task, a task in which a letter displayed on a monitor is matched
      with the letter displayed N letters previously. With increasing N, this task
      places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O
      water were injected into nine normal volunteers. The complete sequence of four
      tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a
      total of 24 injections of 15O-water. We show that the peak count rate performance
      for the HR+ is approached at injected activity levels of 15O-water around 15 mCi.
      For this particular choice of N-back task, robust activation maps can
      nevertheless be obtained with as little as 5 mCi injected dose.

PMID- 9918740
TI  - Biosynthesis, distribution and metabolism of endothelins in the pulmonary system.

PMID- 9918741
TI  - Endothelin receptor subtypes: distribution and function in the lung.

PMID- 9918742
TI  - Blocking of the endothelin system: the development of receptor antagonists.

PMID- 9918743
TI  - Endothelin and the airway mucosa.

PMID- 9918744
TI  - Endothelin-1: a mediator of pulmonary hypertension?

PMID- 9918745
TI  - Respiratory viral infections and the endothelin system.

PMID- 9918746
TI  - Endothelin-1: an interesting peptide or an important mediator in pulmonary
      diseases?

PMID- 9918747
TI  - Effect of novel mixed ETA/ETB antagonists on responses to ET-1 in human small
      muscular pulmonary arteries.
AB  - Selective ETA and ETB receptor antagonists do not fully inhibit responses to ET-1
      in human small pulmonary arteries. Here, we have compared the influence of the
      novel mixed ETA/ETB antagonists SB/217242, SB/234551 and SB/209670 on ET-1
      mediated vasoconstriction in these vessels. ET-1 was a potent vasoconstrictor
      (pEC50: 8.14+/-0.05, n=5) and the concentration-response curve to ET-1 was
      biphasic in nature. All three mixed antagonists (1 microM) inhibited the
      responses to ET-1, abolishing the biphasic form of the concentration response
      curve. The order of potency was SB 209670>SB 234551>/=SB 217242 with estimated
      pKb values of 8.0+/-0.20, 6.8+/-0.17 and 6. 6+/-0.11 respectively (n=3-5).

PMID- 9918748
TI  - Regulation of endothelin-1 at rest and during a short steady-state exercise in 21
      COPD patients.
AB  - Endothelin-1 (ET-1) is a vasoconstrictive peptide which may play a relevant role
      in the pathogenesis of pulmonary hypertension (PH) in COPD patients. We assessed
      the correlations of plasmatic ET-1 levels with pulmonary function data, arterial
      blood gases and pulmonary haemodynamics in 21 COPD patients with moderate to
      severe airway obstruction (FEV1: 1.19+/-0.49 l, mean+/-SD). There were 11
      hypoxemic patients (PaO2 <65 mmHg). Six patients had resting PH (mean pulmonary
      artery pressure >/=20 mmHg). Eight patients had exercising PH (PAP >/=30 mmHg)
      during a short (6 min) 30 W steady state exercise. At rest, arterial ET-1 levels
      were significantly higher in COPD patients with hypoxemia when compared to those
      without hypoxemia (16.6+/-2.7 vs. 12.5+/-3.9 pM/l, P=0.02) and in COPD patients
      with PH when compared to those without PH (16.5+/-3.4 vs. 13+/-3.9 pM/l, P=0.04).
      Resting arterial ET-1 levels were negatively correlated with PaO2 (r=-0.45,
      P=0.05). At rest, the differences between mixed venous and arterial ET-1 levels
      were positively correlated with FEV1 (r=0.54, P=0.024). At exercise, the mean
      arterial ET-1 level was not significantly different from the mean resting ET-1
      level (13.8+/-3.4 vs. 13.3+/-4 p M/l, NS). There were eight COPD patients who had
      decreasing arterial ET-1 levels between rest and the end of a 6 min exercise, and
      six COPD patients who had increasing arterial ET-1 levels. These variations of
      arterial systemic ET-1 levels from rest to exercise were negatively correlated
      with FEV1 (r=-0.66, P=0.01). We conclude that in COPD patients (1) at rest,
      arterial ET-1 levels are increased in hypoxemia or pulmonary hypertension and (2)
      at rest or during exercise, the turn-over of ET-1 may be dependent of the degree
      of the bronchial obstruction.

PMID- 9918749
TI  - Chronic hypoxia increases staurosporine sensitivity of pulmonary artery smooth
      muscle to endothelin-1.
AB  - Endothelins (ET) have been implicated in the pathogenesis of hypoxia-induced
      pulmonary hypertension. We evaluated the contribution of protein kinase C (PKC)
      to the ET-1 response of isolated endothelium-denuded extralobar pulmonary artery
      (PA) from rats exposed to chronic hypoxia (10% O2-90% N2, 1 ATM, 14 days or 28
      days) or air. Hypoxia increased hematocrit (Hct [% above air control]: at 14
      days, by 28+/-2%; after 28 days to 33+/-2%) and the mass ratio of right ventricle
      over left ventricle plus septum (RV/LV+S [% above air control]: at 14 days, by
      54+/-1%; after 28 days to 114+/-13%), an index of right ventricle hypertrophy.
      Hypoxic exposure for 14 days and 28 days decreased PA sensitivity to ET-1 (change
      in EC50: 14 days, four-fold; 28 days, two-fold vs. air controls) and transiently
      decreased the magnitude of maximum ET-1-induced contraction (Emax [% decrease
      from control]: 14 days, 53+/-6%; 28 days, 23+/-6%). Staurosporine, a PKC
      inhibitor, decreased ET-1 sensitivity of PA from 0, 14, and 28 days air-exposed
      rats by four- to nine-fold without affecting Emax. However, staurosporine
      markedly decreased hypoxic PA sensitivity to ET-1 (change in EC50: 14 days, 1700
      fold; 28 days, 55-fold vs. hypoxic controls) and decreased Emax (% decrease from
      hypoxic control: 14 days, 38+/-6%; 28 days, 59+/-7%). In conclusion, hypoxic
      exposure time-dependently varies the responsiveness of PA smooth muscle to ET-1
      and may modulate the contribution of PKC activation.

PMID- 9918750
TI  - Roles of endothelins and their receptors in immune complex
      induced/polymorphonuclear-mediated lung injury (reversed passive arthus reaction)
      in CD-1 mice.
AB  - A number of pro-inflammatory mediators (leukotrienes, platelet activating factor,
      cytokines) participate in the process of neutrophil-dependent lung injury induced
      by immune complexes. Here, we studied the role of endothelins (ET) in the
      reversed passive Arthus reaction (AR) as a model of pneumonitis in CD-1 mice. We
      examined the broncholaveolar lavage fluid (BALF) for signs of inflammation such
      as the accumulation of cells, myeloperoxidase (MPO) activity and hemoglobin (Hb)
      levels, as a measure of hemorrhagic lesions, 24 h after injection. We used a
      selective ETA (BQ-123) or a non-selective ETA/ETB-R (SB 209670) receptor
      antagonist at various concentrations (2.5, 5 or 10 mg/kg ip at -8, 0, 8 and 16 h)
      to assess the involvement of ET. Challenged mice revealed signs of acute
      inflammation and hemorrhagic lesions. Levels of Hb and MPO, total and neutrophil
      cell counts increased by 9-, 9-, 3.2- and 63-fold, respectively. The lower dose
      of SB 209670 reduced Hb levels by 21% (P<0.05), without affecting cell
      accumulation or MPO. The mid-dose had no effect; the highest dose caused 60, 57
      and 70% increases in Hb levels, total cell and neutrophil counts, respectively.
      Conversely, the highest dose of BQ-123 decreased Hb, total cell and neutrophil
      counts and MPO levels by 36, 35, 42 and 70%, respectively. These results support
      a role for ET in AR lung injuries. They also suggests that blocking ETA-R may be
      beneficial, while blockade of ETB-R (using a high dose of SB 209670) may be
      detrimental. A beneficial ETB-mediated response may exist that naturally
      interferes with events triggered by the formation of immune complexes such as
      cell accumulation and their subsequent activation leading to acute lung injury.

PMID- 9918751
TI  - The effect of the ETA receptor antagonist (CI-1020) in rats with established
      hypoxic pulmonary hypertension.
AB  - ETA receptor antagonists have previously been shown to prevent the development of
      pulmonary hypertension induced by chronic hypoxia in the rat. Clinically,
      however, patients present with already established pulmonary hypertension. We
      have investigated the effects of the ETA receptor antagonist CI-1020 in rats
      previously adapted to chronic hypoxia. Two protocols were followed. Rats (n=32)
      were divided into two batches of four groups: normoxic controls in air for 10
      days (NC10), chronic hypoxic controls in hypoxia for 10 days (CHC10), chronic
      hypoxic vehicle treated in hypoxia for 20 days (CHV20) and chronic hypoxic drug
      treated in hypoxia for 20 days (CHT20). Ten days after the onset of hypoxia, oral
      treatment with drug (40 mg/kg per day) or vehicle was started. Animal weight,
      ratio of right ventricular weight to left ventricular weight including septum
      (RV/LV+S) and percentage of double elastic lamina (DEL) were determined. In the
      second study, 12 rats were divided into three groups; normoxic controls in air
      for 20 days (NC20), (CHV20) and (CHT20). After 10 days hypoxia, oral treatment
      with drug (40 mg/kg per day) or vehicle was started. Isolated perfused lung
      preparations were then used to determine pulmonary artery pressure and pulmonary
      vascular resistance. Treatment with CI-1020 reduced the increase in RV/LV+S and
      the percentage DEL induced by chronic hypoxia and significantly lowered the
      increase in pulmonary resistance in isolated perfused lungs from chronically
      hypoxic animals. These results suggest that CI-1020 could have an important role
      in the treatment and reversal of established pulmonary vascular remodelling.

PMID- 9918752
TI  - The ETA antagonist CI-1020 inhibits hypoxic pulmonary vasoconstriction in small
      isolated rat pulmonary arteries.
AB  - Hypoxic pulmonary vasoconstriction (HPV) of rat pulmonary arteries in vitro
      occurs in four phases. Initial vasodilation (phase 1), is followed by transient
      contraction (phase 2), further vasodilation (phase 3) and finally a second
      sustained contraction (phase 4). We have investigated the role of ET-1 in HPV
      using the ETA receptor antagonist CI-1020. Small rat pulmonary arteries (SPA,
      n=32, diameter=454+/-22 microM) were mounted in a wire myograph. Two contractions
      to 80 microM KCl ensured response reproducibility and relaxation to 10 microM
      acetyl choline following constriction with 100 microM prostaglandin F2alpha
      (PGF2alpha) to indicate endothelial integrity. A control hypoxic response was
      produced following priming with 5 microM PGF2alpha. Vessels (n=8) were then
      exposed to either vehicle or CI-1020 (1, 10 or 100 microM) for 30 min in the dark
      before re-exposure to PGF2alpha and hypoxia. Responses were standardized as a
      percentage of contraction to 80 mM KCl. Vehicle caused an increase in phase 2 of
      HPV of +2.51+/-4.20% (expressed as difference between pre- and post-drug values).
      CI-1020 (1, 10 and 100 microM) caused a significant reduction in phase 2 of HPV
      of -9. 76+/-1.40%, -9.23+/-2.30% and -7.96+/-1.70%, respectively (P<0.05). These
      results suggest that phase 2 of HPV in rat SPA is attributed, in part, to the
      action of ET-1 at the ETA receptor.

PMID- 9918753
TI  - Fenfluramine potentiates canine pulmonary vasoreactivity to endothelin-1.
AB  - The appetite suppressant fenfluramine, a serotonin uptake inhibitor, has been
      implicated in the development of primary pulmonary hypertension (PPH). The effect
      of fenfluramine on the pressor response to endothelin-1 (ET-1) in the canine
      pulmonary circulation was determined using the isolated perfused dog lung.
      Pulmonary vascular resistance was measured using vascular occlusion techniques.
      Group 1 (n=4) consisted of isolated lung lobes treated with 10(-8)M ET-1 alone.
      For group 2 (n=4) and group 3 (n=4), dogs were given 15 mg fenfluramine daily for
      14 days prior to sacrifice for isolated lung perfusion. In group 2, lobes were
      treated with 10(-7)M fenfluramine after lung isolation. In group 3, the isolated
      lobes were treated with 10(-8)M ET-1 similar to group 1. Acute treatment of the
      isolated lobes in group 2 with 10(-7)M fenfluramine increased pulmonary arterial
      pressure. In group 3, administration of 10(-8)M ET-1 potentiated the effect of ET
      1 on post-capillary resistance relative to group 1, and elicited an increase in
      precapillary resistance, an effect not present in group 1. These results indicate
      that chronic fenfluramine exposure potentiates the pulmonary vasoconstrictor
      response to ET-1, and suggests that elevated levels of serotonin may <<prime>>
      the pulmonary circulation to become hyperreactive to other vasoactive substances
      possibly leading to the development of disease states such as primary pulmonary
      hypertension.

PMID- 9918754
TI  - Increased reactivity to endothelin of pulmonary arteries in long-term post
      obstructive pulmonary vasculopathy in rats.
AB  - Post-obstructive pulmonary vasculopathy (POPV) describes the constellation of
      findings following chronic ligation of one pulmonary artery, including bronchial
      angiogenesis, pulmonary vasculopathy and increased vasoreactivity to
      pharmacologic agents. Previously, we found in rats with POPV of 28 days duration
      that maximal responses to endothelin-1 (ET-1) and ET-3 of pulmonary arteries but
      not veins were increased, and that relaxation of arteries to ET-1 was reduced,
      attributable to an elevated proportion of ETA over ETB receptors. To determine
      the reactivity of pulmonary vessels and airways to ET in protracted POPV, we
      ligated the left main pulmonary artery of nine rats. Eleven months later, using a
      lung explant technique, we compared contractile responses of pulmonary vessels
      and airways to ET-1 and ET-3 in POPV lungs with controls. Morphometric
      measurements were made on the vessels, and immunoreactivity to ET-1 and
      endothelin converting enzyme (ECE-1) studied. We found contractile responses to
      ET-1 and ET-3 significantly increased in arteries, but not veins or airways.
      Morphometry showed arteries and veins had reduced diameters with muscle
      thickening only in veins. Expression of ET-1 and ET-3 in vascular endothelial
      cells and airway epithelial cells were not altered significantly. Our data
      suggest that protracted POPV selectively enhanced the contractility of pulmonary
      arteries to ET, and is not attributable to medial muscle thickening.

PMID- 9918755
TI  - Enhancement of aortic contractility by endothelin following prolonged hypoxia in
      vivo.
AB  - The purpose of this study was to determine if endothelin-1 (ET-1) mediates
      endothelium-dependent enhancement of rat aortic contractility following exposure
      to hypoxia. Rats breathed room air or 10% oxygen for 12 or 48 h. Thoracic aortas
      and plasma were analysed for ET-1 content by radioimmunassay. Aortic rings were
      mounted in organ bath myographs for measurement of isometric tension during
      activation by phenylephrine (10(-9)-10(-4) M), in the presence and absence of BQ
      123. In some rings, the endothelium was removed. Plasma ET-1 levels were 0.79+/
      0.09 pg/ml, 2.00+/-0.36 and 1.88+/-0.21 pg/ml, in normoxic rats and rats exposed
      to hypoxia for 12 or 48 h respectively (P<0.001, 12 or 48 h vs. control). Aortic
      ET-1 concentrations were 202.3+/-20.8 fg/mg in normoxic rats, compared to 274.9+/
      40.6 fg/mg and 292.4+/-24.4 fg/mg in rats exposed to hypoxia for 12 and 48 h,
      respectively (P<0.01, 12 or 48 h vs. control) and 155.0+/-43.1 fg/mg in de
      endothelialized aortas from rats exposed to hypoxia for 48 h (P>0.05 vs. normoxic
      controls). Maximum tension during phenylephrine-induced contraction was 0.46+/
      0.04 mg/g and 0.33+/-0.03 mg/g in endothelialized rings from rats exposed to
      hypoxia for 48 h in the presence and absence of BQ-123, respectively (P<0.05 for
      difference), and 0.28+/-0.07 mg/g in rings in which the endothelium had been
      removed. Local endothelin release is an important mechanism by which the
      responsiveness of the systemic vasculature to agonists may be preserved during
      hypoxia.

PMID- 9918756
TI  - cGMP inhibition of endothelin-stimulated inositol phosphate production in the
      fetal lamb pulmonary artery.
AB  - Endothelin-1 (ET-1) stimulates inositol phosphate production in vascular smooth
      muscle. In the present study, interactions between cyclic GMP (cGMP), cyclic AMP
      (cAMP) and ET-1 in fetal lamb pulmonary arteries were investigated using
      phosphoinositide hydrolysis studies and tissue bath techniques. ET-1 was found to
      be a potent vasoconstrictor of these vessels, with an EC50 of 15.8 nM. ET-1
      stimulated total inositol phosphate (IP) production; basal IP production was 68
      cpm/mg vs. 247 cm/mg with 1 microM ET-1. 8-bromo-cGMP (2 mM) significantly
      increased the threshold of ET-1 concentration for pulmonary artery contraction,
      but had no effect on IP production. Zaprinast (a selective type V
      phosphodiesterase inhibitor, 60 microM) did not affect ET-1-induced contractility
      or IP production. IBMX (0.5 mM), a non-specific phosphodiesterase inhibitor,
      inhibited the potent and maximal effects of ET-1 in arterial contraction and
      decreased ET-1-stimulated IP production by 49%, while forskolin had a lesser
      effect in the tissue bath and no effect on IP production. Thus, 8-bromo-cGMP and
      IBMX alter the contractile effects of ET-1 in the fetal pulmonary artery and IBMX
      also inhibits inositol phosphate production. The cross-talk mechanisms of these
      agents require further investigation.

PMID- 9918757
TI  - Endothelin-1 activates MAP kinases and c-Jun in pulmonary artery smooth muscle.
AB  - We tested the coupling of endothelin receptors to mitogen-activated protein
      kinases (MAPK) and nuclear factor c-Jun in intact canine pulmonary artery smooth
      muscle. Muscle rings denuded of endothelium were stimulated with 10(-7)M ET-1 and
      frozen during contraction. An <<in-gel>> kinase assay with myelin basic protein
      as substrate revealed protein kinase activities at 98, 75, 55, 50, 44 and 40 kDa.
      Erk1 and Erk2 MAPK were activated by ET-1 to 5.4+/-0.97 and 4.03+/-1. 54 times
      basal activity at 10 min. Using phospho-specific antibodies, we found increased
      threonine/tyrosine phosphorylation of p38 and JNK1 MAPK to 2.04+/-0.47 and 2.56+/
      0.72 times basal. ET-1 increased the phosphorylation level of nuclear factor c
      Jun with a time-course closely matching the activation of JNK1 and p38 MAPK.
      Therefore, endothelin receptors initiate intracellular signals leading to
      activation of Erk, p38 and JNK1 MAPK pathways and ultimately to nuclear targets.
      The activation of JNK1 MAPK seems closely related to the phosphorylation of
      nuclear transcription factor c-Jun.

PMID- 9918758
TI  - Characterization of the enzyme involved in the processing of big endothelin-1 in
      human lung epithelial cells.
AB  - Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the
      inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The
      aim of this study was to characterize in airway and alveolar epithelial cells the
      enzymes responsible for this activation. BEAS-2B and A549 cells, which both
      produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells,
      respectively. Both cell lines were able to convert exogenously added Big ET-1
      (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing.
      The conversion was inhibited by phosphoramidon in both cell lines with an IC50
      approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral
      endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B
      and A549 cells was not inhibited by thiorphan, and phosphoramidon showed
      inhibition only at high concentration (>100 microM). Western blotting following
      electrophoresis in reducing conditions demonstrated a protein of MR 110
      corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in
      whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b
      and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B
      and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE
      1 and that isoforms 1b and 1c could be involved in this processing with no
      significant role of NEP.

PMID- 9918759
TI  - Endothelin-1 expression during early response after antigen challenge in brown
      norway rats.
AB  - The objective of this study is to investigate if endothelin-1 (ET-1) gene
      expression changes during the early response phase following antigen challenge.
      We used sensitized Brown-Norway rats known to develop an early airway response
      after antigen challenge. After ovalbumin challenge, sensitized rats presented an
      early response, characterized by an increase in pulmonary pressure (209+/
      14.53%,P<0. 01) and diminished functional parameters (inspiratory capacity,
      forced vital capacity (FVC) and expiratory flow at 75% of FVC), compared to their
      respective basal values. ET-1 mRNA expression was assessed by reverse
      transcription and polymerase chain reaction using specific primers for prepro-ET
      1. A group of unsensitized rats was used as control. ET-1 expression was
      significantly enhanced in sensitized rats during the early response (290+/
      62%,P<0.01) compared to the control group. In conclusion, antigen challenge
      induces an activation of ET-1 gene expression during the early response in Brown
      Norway rats, suggesting a contribution of this protein to the development of
      bronchoconstriction.

PMID- 9918760
TI  - Effect of endothelin receptor antagonists (BQ-485, Ro 47-0203) on collagen
      deposition during the development of bleomycin-induced pulmonary fibrosis in
      rats.
AB  - Previous evidence suggests a role for endothelin-1 (ET-1) in the pathogenesis of
      pulmonary fibrosis. To determine if ET-1 regulates collagen deposition in
      pulmonary fibrosis, we examined the effect of the non-selective ETA and ETB
      receptor antagonist bosentan (Ro 47-0203), and a selective ETA receptor
      antagonist, BQ-485, on collagen deposition during the development of bleomycin
      induced pulmonary fibrosis in rats. Lung collagen content, derived from
      measurements of hydroxyproline and expressed as mg collagen/lung, was increased
      in the bleomycin-treated animals by day 7 (bleomycin, 22.88+/-1.46; control
      18.50+/-0.98; P<0.05), continued to increase up to day 14 (bleomycin, 38.80+/
      2.17; control 22.57+/-0.77; P<0.001) and then remained constant to 21 days. Daily
      treatment by gavage with bosentan (100 mg/kg) did not prevent the increase in
      collagen deposition induced by instillation of bleomycin at any of the times
      measured. Continuous administration of BQ-485, by subcutaneously implanted
      minipump (7.5 mg/day), also failed to prevent the bleomycin-induced collagen
      deposition at 14 days. These findings suggest that ET-1 does not modulate
      collagen deposition during the development of bleomycin-induced pulmonary
      fibrosis. Further studies are required to assess whether endothelin receptor
      antagonists modulate other components of the fibrotic response or play a role in
      man.

PMID- 9918761
TI  - Effect of isoflurane on endothelin-1 mediated airway smooth muscle contraction.
AB  - Endothelin-1 (ET-1) is an endogenously produced 21 amino acid peptide that can
      cause significant airway smooth muscle (ASM) constriction. Volatile anesthetics
      e.g. isoflurane, can attenuate ASM constriction. This investigation was
      undertaken to study the direct effects of isoflurane, at a clinically relevant
      dose, on endothelin-induced constriction in rat trachea. Five Sprague-Dawley
      female rats (weight 325-350 g) were euthanized. Four 2-3 mm rings were excised
      from the mid portion of the trachea, attached to a force transducer for isometric
      measurement, and were then suspended in jacketed baths containing 37 degreesC KH
      solution, bubbled with 95% O2 and 5% CO2. Carbachol dose-response curves (10(-8)
      10(-4)M) were obtained to establish the maximal contractility (Cmax) for each
      tracheal ring. Carbachol was then washed out of the bath solution until the
      tissue tension returned to the baseline. Subsequently, ET-1 dose response curves
      (3-200 nM) were generated in the absence (ET-1, control) and in the presence of
      2% isoflurane. Our data suggests that isoflurane at 2% concentration, attenuated
      ET-1 induced tracheal contraction at 100 and 200 nM concentrations by 20%. This
      is the first demonstration indicating that, at a clinically relevant dose,
      isoflurane depresses ET-1 induced ASM constriction.

PMID- 9918762
TI  - Variations in systemic and pulmonary endothelin-1 in horses with recurrent airway
      obstruction (heaves).
AB  - Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that
      represents a major cause of morbidity and loss of performance. The exact
      pathogenesis of asthma in man is unclear but the role of endothelin (ET) is
      currently under investigation, thus sparking interest in the bronchoconstrictive
      and vasoconstrictive properties of endothelin in the equine-specific disease
      entity. In this study, we investigated the levels of ET-1 in systemic blood, as
      well as in bronchoalveolar lavage (BAL) from horses with RAO. We also studied how
      these values might correlate with those of lung function tests and pulmonary
      artery pressure. Five horses with RAO were evaluated both in remission and in
      crisis and compared to five control horses. RAO horses had significantly (P<0.05)
      higher systemic ET-1 levels than control horses. They also had a negative
      arteriovenous ET-1 difference that may correspond to a net uptake of ET-1 in the
      lung. RAO horses in crisis had increased amounts of immunoreactive ET in BAL
      fluid compared to normal control subjects. Additionally, the reduction in lung
      function seen in RAO horses in crisis was significantly correlated with lower
      epithelial lining fluid ET-1 levels. Our results demonstrate that endothelin may
      contribute to the pathogenesis of asthma.

PMID- 9918763
TI  - Adenosine-induced inhibition of basal endothelin-1 production from guinea-pig
      tracheal epithelial cells: a mechanism involving the release of cAMP.
AB  - Guinea-pig tracheal epithelial cells, like other pulmonary cells in various
      species, have been reported to synthesize and release endothelins (ET). Their
      production is inducible by many agents and inhibited by ET-converting enzyme
      inhibitors, corticosteroids and beta agonists. Here, we studied the effect of
      adenosine on (1) the formation of adenosine 3', 5'-cyclic monophosphate (cAMP)
      and (2) concomitant effect on the basal release of ET from primary cultured
      tracheal epithelial cells isolated from guinea-pigs (GPTEpC). Adenosine (10(-7)
      10(-3) M), the endogenous non-selective purinergic receptor agonist, induced the
      production of cAMP in a concentration-dependent manner (pD2=4.99+/-0.09).
      Concomitantly, adenosine decreased by a maximum of 39% ET-1-production over the
      same concentration range (with a 96% correlation). The inhibitory effect over ET
      1-production was abolished by CGS15943 (10(-4) M), a non-selective A1/A2A
      receptor antagonist, and a xanthine amine congener (10(-4) M), a selective A1
      receptor antagonist. Thus, these results suggest that adenosine attenuates the
      production of ET-1 from GPTEpC by stimulating the release of cAMP via the direct
      activation of adenosine receptors.

PMID- 9918765
TI  - Calcium and organelles: a two-sided story.

PMID- 9918766
TI  - Dithionite reduced carbon monoxide complex of cytochrome P450cam is a monomer.
AB  - Sedimentation experiments on cytochrome P450cam (CYP101) has been performed to
      compare the molecular mass of the protein in the oxidized state and as carbon
      monoxide complex. The oxidized protein in the absence of beta-mercaptoethanol is
      a dimer with a molecular mass of 92 kDa. Addition of mercaptoethanol avoids
      completely the dimerization. Dithionite reduced P450cam in the presence of carbon
      monoxide has been found to be a monomeric protein.

PMID- 9918768
TI  - Expression of transposon LINE-1 is relatively human-specific and function of the
      transcripts may be proliferation-essential.
AB  - A new 1.7-kb LINE (L1) transcript has been discovered from the cDNA library of
      human small-cell lung cancer. The nucleotide sequence of 1.7-kb L1 transcript is
      98.4% similar to that of open reading frame 2 (ORF2) found in consensus complete
      6.5-kb L1. Although L1 DNA segments could be detected from both genomic DNAs of
      human and rodent cells by PCR, these L1 transcripts were not detectable from
      cellular RNA of rodent cells by RT-PCR and northern hybridization, implying that
      the expression of L1 was relatively human-specific. The functions of L1
      transcripts in cells are not yet clear. This paper shows that L1 transcripts are
      essential for cell proliferation when determined by antisense oligonucleotides.
      Alternately, L1 transcripts exhibit in all human cells we have examined so far,
      and they map to all the human chromosomes. A sequence-similarity search in the
      GenBank database indicates that the major sequence of 1.7-kb L1 is integrated in
      human retinoblastoma (Rb), IL-2, and factor VIII genes. Since Rb and factor VIII
      genes have displayed high frequency of chromosomal deletions in various cancers
      and haemophilia A, the universal integration of long and homologous L1 segments
      in the genes and all chromosomes may be liable to promote abnormal DNA
      rearrangement.

PMID- 9918767
TI  - C-terminal threonine phosphorylation activates ERM proteins to link the cell's
      cortical lipid bilayer to the cytoskeleton.
AB  - The plasma membrane consists of a lipid bilayer with integral membrane proteins
      stabilized by regulated linkages to the cortical actin cytoskeleton. The
      regulation is necessary for cells to change shape ormigrate. The ERM (ezrin
      radixin-moesin) proteins are believed to provide such links, with the N-terminal
      halves associating with integral membrane proteins, either directly or indirectly
      through adapter molecules like EBP50 (ERM binding phosphoprotein, 50 kDa), and
      their C-terminal halves associating with F-actin. However, isolated ERM proteins
      largely exist in a dormant state by virtue of an intramolecular interaction
      between amino- and carboxyl-terminal domains, thereby masking membrane and
      cytoskeletal association sites. C-terminal threonine phosphorylation of a
      fragment of radixin has been found to destroy its ability to bind the amino
      terminal domain without affecting the C-terminal F-actin binding site. Here we
      show that C-terminal phosphorylation of full-length, dormant ezrin and moesin by
      protein kinase C-theta simultaneously unmasks both the F-actin and EBP50 binding
      sites. Increased phosphorylation of moesin in cells correlated with increased
      association of moesin with the cortical actin cytoskeleton. These results show
      that activation of ERM proteins can be accomplished by phosphorylation of a
      single C-terminal threonine residue.

PMID- 9918769
TI  - Non-enzymatic production of nitric oxide (NO) from NO synthase inhibitors.
AB  - The gaseous signal molecule, nitric oxide (NO*), is generated enzymatically by NO
      synthase (NOS) from L-arginine. Overproduction of NO contributes to cell and
      tissue damage as sequelae of infection and stroke. Strategies to suppress NO
      synthesis rely heavily on guanidino-substituted L-arginine analogs (L-NAME, L-NA,
      L-NMMA, L-NIO) as competitive inhibitors of NOS, which are often used in high
      doses to compete with millimolar concentrations of intracellular arginine. We
      show that these analogs are also a source for non-enzymatically produced NO.
      Enzyme-independent NO release occurs in the presence of NADPH, glutathione, L
      cysteine, dithiothreitol and ascorbate. This non-enzymatic synthesis of NO can
      produce potentially toxic, micromolar concentrations of NO and can oppose the
      effects of NOS inhibition. NO production driven by NOS inhibitors was
      demonstrated ex vivo in the central nervous and peripheral tissues of gastropod
      molluscs Aplysia and Pleurobranchaea using electron paramagnetic resonance and
      spin-trapping techniques. These results have important implications for
      therapeutic regulation of NO homeostasis.

PMID- 9918770
TI  - Association of Shc, Cbl, Grb2, and Sos following treatment with 2,3,7,8
      tetrachlorodibenzo-p-dioxin in primary rat hepatocytes.
AB  - c-Src kinases and p21 Ras are known to be implicated in 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-mediated signal transduction. However, the
      effects of TCDD on the molecular interaction of adaptor complex in the protein
      tyrosine kinase signaling cascade have not been reported. The present study is
      designed to clarify whether TCDD modulates the molecular interactions of Shc,
      Cbl, Grb2, and Sos in primary rat hepatocytes. TCDD causes an electrophoretic
      mobility shift of Sos and increases Sos/Grb2 association. Tyrosine phosphorylated
      Shc, mainly p52, unloads to the Grb2/Sos complex upon TCDD stimulation.
      Interestingly, TCDD decreases the tyrosine phosphorylation level of Cbl, although
      Cbl recruits more Grb2 and Shc proteins by TCDD. These results indicate that TCDD
      modulates the molecular interaction of adaptor complex proteins including Shc,
      Grb2, Sos, and Cbl. Furthermore, tyrosine phosphorylation of Cbl may not be
      critical for interaction of the protein with Grb2 and Shc in the TCDD signaling
      pathway in primary rat hepatocytes.

PMID- 9918771
TI  - Analysis of active site residues of the antiviral protein from summer leaves from
      Phytolacca americana by site-directed mutagenesis.
AB  - The summer leaf isoform of the pokeweed (Phytolacca americana) antiviral protein,
      PAP II, was produced in high yields from inclusion bodies in recombinant E. coli.
      On the basis of its sequence similarity with the spring leaf isoform (PAP I) and
      with the A chain of ricin, a three-dimensional model of the protein was
      constructed as an aid in the design of active site mutants. PAP II variants
      mutated in residues Asp 88 (D88N), Tyr 117 (Y117S), Glu 172 (E172Q), Arg 175
      (R175H) and a combination of Asp 88 and Arg 175 (D88N/R175H) were produced in E.
      coli and assayed for their ability to inhibit protein synthesis in a rabbit
      reticulocyte lysate. All of these mutations had effects deleterious to the
      enzymatic activity of PAP II. The results were interpreted in the light of three
      reaction mechanisms proposed for ribosome-inactivating proteins (RIPs). We
      conclude that none of the proposed mechanisms is entirely consistent with the
      data presented here.

PMID- 9918772
TI  - A novel mutant loxP containing part of long terminal repeat of HIV-1 in spacer
      region: presentation of possible target site for antiviral strategy using site
      specific recombinase.
AB  - A site-specific recombinase Cre is responsible for the recombination at a 34 bp
      loxP site. This system has been investigated for the antiviral strategy to excise
      proviral DNA from retrovirus-infected cells. It was reported that loxP sites
      could be inserted into long terminal repeat (LTR) of retrovirus to delete
      proviral DNA. To apply this system to human immunodeficiency virus type 1 (HIV-1)
      without inserting any DNA, one 34 bp sequence was selected from LTR of
      recombinant HIV-1 clone, loxLTR-1, based on sequence similarity between LTR and
      loxP, and sequence arrangement of 8 bp middle part in 34 bp LTR segment. When the
      8 bp spacer region of loxP was changed into the corresponding middle part of
      loxLTR-1, this variant loxP would allow Cre to specifically recombine between
      themselves but not with wild-type loxP in vitro. This study suggests that site
      specific excision of proviral DNA of HIV-1 could be catalyzed by the least
      modified Cre recognizing the loxLTR-1 sites.

PMID- 9918773
TI  - An ELISA for RNA helicase activity: application as an assay of the NS3 helicase
      of hepatitis C virus.
AB  - A convenient enzyme-linked immunosorbent assay (ELISA) for RNA helicase activity
      was developed with principles similar to the standard assay. The helicase ELISA
      utilizes a non-radioactive double-stranded substrate with a biotin-labeled
      template (long) strand hybridized to a digoxigenin (DIG)-labeled release (short)
      strand. The template strand binds to the wells of streptavidin-coated microtiter
      plates (SA-MTP) where the helicase catalyzes the unwinding reaction. Substrate
      not unwound retains the DIG-labeled release strand and is detected using anti-DIG
      coupled to horseradish peroxidase. Chromogenic detection follows. Absorbance
      measurement allows determination of unwinding efficiency of reactions. To
      demonstrate effectiveness, the ELISA-based assay was used to study the unwinding
      activity of the hepatitis C virus (HCV) NS3 helicase. Using a known inhibitor of
      NS3 helicase activity and two mutant HCV helicases, the ability of the assay to
      screen potential anti-helicase drugs and putative helicases is illustrated. The
      helicase ELISA is more convenient than the standard helicase assay and is
      especially suited for the testing of large numbers of samples.

PMID- 9918774
TI  - Antimicrobial peptides of the brevinin-2 family isolated from gastric tissue of
      the frog, Rana esculenta.
AB  - Four structurally related peptides with potent growth-inhibitory activity towards
      Escherichia coli were isolated from an extract of the stomach of the European
      green frog Rana esculenta, and were identified as members of the brevinin-2
      family. Two peptides, termed brevinin-2Eg (GIMDTLKNLA10 KTAGKGALQS20 LLNHASCK
      LS30GQC) and brevinin-2Eh (GIMDTLKNLA10 KTAGKGALQS20 LLNHASCKL S30 KQC) have not
      been described previously. One peptide is identical to brevinin-2Ec, previously
      isolated from R. esculenta skin secretions, and one peptide is identical to
      brevinin-2Ef whose structure has been deduced from a cloned cDNA prepared from a
      R. esculenta skin cDNA library. The data demonstrate that certain peptides of the
      brevinin-2 family, like the magainins in the toad, Xenopus laevis, may play an
      important role in protecting the gastrointestinal tract of Ranid frogs against
      microbial invasion.

PMID- 9918775
TI  - Isolation of HIV-1 protease-inhibiting peptides from thermolysin hydrolysate of
      oyster proteins.
AB  - The peptides inhibiting HIV-1 protease were isolated from the hydrolysate of
      oyster (Crassostrea gigas) proteins prepared with thermolysin. The amino acid
      sequences of the peptides were determined as Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu
      Glu-Tyr-Ser-Leu. These sequences exist in some proteins of variola major virus or
      human cytomegalovirus. Chemically synthesized Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu
      Glu-Tyr-Ser-Leu showed IC50 values of 20 and 15 nM, respectively, and behaved as
      competitive inhibitors for HIV-1 protease with Ki values of 13 and 10 nM,
      respectively. These peptides were more potent as an HIV-1 protease inhibitor than
      pepstatin A.

PMID- 9918776
TI  - CDK4, a possible critical regulator of apoptosis in rat pheochromocytoma PC12
      cells.
AB  - The function of cell cycle regulator molecules during apoptosis induced by serum
      withdrawal was examined in rat pheochromocytoma PC12 cells. When human cDNAs
      encoding cyclins, cyclin-dependent kinase 2 (CDK2), CDK4, and cell-division cycle
      2 (CDC2), were introduced, only CDK4-overexpressing cells were more prone to
      apoptosis compared with parental cells. In the parental cells, serum withdrawal
      resulted in the upregulation of CDK4 protein expression 6.6-fold for the first 12
      h after serum withdrawal. In contrast, CDK4 protein levels in CDK4-overexpressing
      cells remained constant for the first 12 h followed by a gradual decline.
      Expression of cyclin D1 was upregulated in both cell lines. The change in CDK4
      kinase activity almost paralleled that of CDK4 protein expression. These results
      suggest that CDK4 kinase activity is one of the critical regulators in the
      apoptotic cascade in PC12 cells.

PMID- 9918777
TI  - A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo
      hydroxyl radical generation.
AB  - In the current study, we characterized a urinary melatonin metabolite which could
      provide a safe and effective method to monitor generation of HO* in humans. Using
      mass spectrometry (MS), proton nuclear magnetic resonance (1H NMR), COSY 1H NMR
      analysis, and calculations on the relative thermodynamic stability, a novel
      melatonin metabolite was identified as cyclic 3-hydroxymelatonin (3-OHM). 3-OHM
      is the product of the reaction of melatonin with HO* which was generated in two
      different cell-free in vitro systems. Interestingly, this same metabolite, 3-OHM,
      was also identified in the urine of both rats and humans. A proposed reaction
      pathway suggests that 3-OHM is the footprint product that results when a
      melatonin molecule scavenges two HO*. When rats were challenged with ionizing
      radiation which results in HO* generation, urinary 3-OHM increased dramatically
      compared to that of controls. These results strongly indicate that the quantity
      of 3-OHM produced is associated with in vivo HO* generation. Since melatonin
      exists in virtually all animal species and has a wide intracellular distribution
      and 3-OHM is readily detected noninvasively in urine, we suggest that 3-OHM is a
      valuable biomarker that can be used to monitor in vivo HO* levels in humans and
      other species. The measurement of urinary 3-OHM as a biomarker of HO* generation
      could provide clinical benefits in the diagnosis and treatment of diseases.

PMID- 9918778
TI  - A peptide corresponding to residues Asp177 to Asn208 of human cyclin A forms an
      alpha-helix.
AB  - Cyclins are essential activators of eukaryotic cell cycle-regulating enzymes
      called cyclin-dependent kinases (CDKs). The binding of cyclins to CDKs is
      mediated by a structural motif comprising a five-helix bundle called the cyclin
      fold and an additional helix (the N-terminal alpha-helix) located N-terminal to
      the cyclin fold. In this work, we examine, using CD and NMR spectroscopy, the
      structure of a 32-residue synthetic peptide derived from the segment (Asp177 to
      Asn208) corresponding to the N-terminal alpha-helix of human cyclin A. CD
      spectroscopic analysis of the peptide revealed that trifluoroethanol (TFE) can
      induce the peptide to assume a stable alpha-helix conformation. Two-dimensional
      1H NMR spectroscopy showed that the alpha-helix is formed by the Asp181 to Cys193
      segment of the peptide. The alpha-helical structure of the peptide in the TFE/H2O
      cosolvent was found to be identical to that in the crystal structure of intact
      cyclin A. Taken together, these results suggest that the N-terminal alpha-helix
      of cyclins may exist as an independent structural unit that plays essential
      functional roles in activating CDKs.

PMID- 9918779
TI  - Characterization of the gene encoding the catalytic subunit of the DNA polymerase
      alpha from Toxoplasma gondii.
AB  - The gene encoding the catalytic subunit of the Toxoplasma gondii DNA polymerase
      alpha enzyme has been isolated. The coding region is 6487 bp in length,
      containing three introns, and specifies a protein of 1690 aa. The seven conserved
      regions which characterize the polalpha polypeptide, as well as four of the five
      polalpha-specific aa domains, were found in the T. gondii gene. The absence of
      one of these domains, as well as the presence of a unique cysteine cluster
      between domains IV and B in the T. gondii polalpha, may result in a slight
      difference in the secondary or even tertiary structure compared with the human
      homologue and thus may be suitable for designing anti-Toxoplasma drugs. A number
      of amino acid differences within the seven conserved regions between the human
      and T. gondii polalpha, as well as variations in the spacings of these regions,
      were also observed.

PMID- 9918780
TI  - Unrestricted agonist activity on murine and human cells of a lipopeptide derived
      from IFN-gamma.
AB  - We describe the isolation of a synthetic agonist of IFN-gamma (L-mIFN-gamma-CT)
      active on mouse and human cells. Its biological activity is the result of the
      ability of the C-terminal extremity of murine IFN-gamma to interact with the
      intracellular part of IFNgamma-R and the observation that the modification of
      peptides by a palmitic acid enables their cytoplasmic delivery. L-mIFN-gamma-CT
      stimulated murine cells exhibited an increase in MHC class II molecules and
      FcgammaRII/III expression and conferred protection against viral lysis.
      Unresponsiveness to L-mIFN-gamma-CT of cells recovered from IFNgamma-R alpha
      chain knockout mice indicated the involvement of IFNgamma-R in the biological
      activities observed. Induction of VCAM-1, ICAM-1, and HLA-DR expression on human
      cells stimulated with L-mIFN-gamma-CT demonstrated an abrogation of species
      specificity. These results describe the development of a new synthetic agonist of
      IFN-gamma, which substitutes for the native cytokine in any IFN-gamma responsive
      cells, by acting intracellularly on IFN-gammaR.

PMID- 9918781
TI  - Interaction between mitochondrial precursor proteins and cytosolic soluble
      domains of mitochondrial import receptors, Tom20 and Tom70, measured by surface
      plasmon resonance.
AB  - We studied the interaction between mitochondrial precursor proteins and
      postulated mitochondrial surface receptor proteins, Tom20 and Tom70, by using a
      methodology of surface plasmon resonance. For these studies, import-competent
      mitochondrial precursor proteins, pCOXIV-DHFR and pSu9-DHFR, and cytosolic
      domains of the two receptor proteins were separately expressed in and purified
      from E. coli cells as a soluble form. By measuring surface plasmon resonance,
      both of the purified precursor proteins were found to specifically bind to either
      of the cytosolic domains of import receptors immobilized on a sensor chip. On the
      other hand, import-incompetent SynB2-DHFR and DHFR itself were shown to possess
      little or no binding abilities to the sensor chip, respectively. Using this
      system, we could demonstrate that the proposed carboxy-terminal acidic bristle
      domain of Tom20 is not essential for the precursor binding. Chemical modification
      of the acidic amino acid residues of either cytosolic domain on the sensor chip
      partially inhibited the binding of pSu9-DHFR, whereas the binding of pCOXIV-DHFR
      was almost unaffected. These results suggest that distinct set of amino acid
      residues of the receptor proteins might be responsible for the binding of
      different precursor proteins.

PMID- 9918782
TI  - Involvement of K+ATP channels in nitric oxide-induced inhibition of spontaneous
      contractile activity of the nonpregnant human myometrium.
AB  - Nitric oxide (NO), an important endogenous substance, is known to be a strong
      relaxant of smooth muscle, including myometrium. It has been postulated that the
      relaxing effect of NO on smooth muscle is achieved by the stimulation of soluble
      guanylyl cyclase, which leads to an increase in the cyclic guanosine 3',5'
      monophosphate (cGMP) levels and hyperpolarization of the cellular membrane. The
      aim of our study was to investigate the involvement of K+ATP channels in the
      mechanism of cGMP-independent nitric oxide-induced inhibition of contractile
      activity of the nonpregnant human myometrium, obtained at hysterectomy. Nitric
      oxide's influence on contractile activity was recorded in the presence of
      methylene blue and glybenclamide, blockers of soluble guanylyl cyclase and K+ATP
      channels, respectively. Nitric oxide, generated by the NO donor DEA/NO, caused a
      dose-dependent inhibition of the spontaneous contractile activity of human
      nonpregnant myometrium. Preincubation with methylene blue (5 microM) did not
      prevent NO-induced relaxation of uterine strips, while 1.5 microM glybenclamide
      blocked this effect. Our results indicate that nitric oxide relaxes human non
      pregnant uterus through K+ATP channels, independent of the cGMP pathway.

PMID- 9918783
TI  - Pentaerithrityl tetranitrate and its phase I metabolites are potent activators of
      cellular cyclic GMP accumulation.
AB  - Using pig kidney epithelial cells (LLC-PK1), the present study assesses the
      cyclic GMP stimulatory effect of pentaerithrityl tetranitrate and its metabolites
      in comparison to other therapeutically used nitric oxide donors. Pentaerithrityl
      tetranitrate was found to be the most potent activator of cyclic GMP synthesis
      compared to other clinically relevant organic nitrates (glyceryl trinitrate,
      isosorbide dinitrate, isosorbide-5-mononitrate). The phase I metabolite
      pentaerithrityl trinitrate was equipotent with its parent compound in stimulating
      cyclic GMP. The concentration-response curves of pentaerithrityl dinitrate and
      isosorbide dinitrate for cyclic GMP accumulation were virtually identical. In
      contrast, pentaerithrityl mononitrate and the phase II metabolite pentaerithrityl
      trinitrate glucuronide did not alter basal cyclic GMP levels. It is concluded
      that the long-term vasodilatory and antiischemic effects of pentaerithrityl
      tetranitrate are caused to a substantial extent by cyclic GMP-mediated actions of
      its pharmacologically active phase I metabolites.

PMID- 9918784
TI  - Nitrilase catalyzes amide hydrolysis as well as nitrile hydrolysis.
AB  - While amides were reported to be completely inert as substrates for all
      nitrilases reported to date, the nitrilase from Rhodococcus rhodochrous J1, which
      catalyzes the hydrolytic cleavage of the C-N triple bond in nitrile to form acid
      and ammonium, was surprisingly found to catalyze hydrolysis of amide to acid and
      ammonium stoichiometrically. This nitrilase exhibited a Km of 2.94 mM for
      benzamide, similar to that for benzonitrile as the original substrate (2.10 mM),
      but the Vmax for benzamide was six orders of magnitude lower than that for
      benzonitrile. Benzamide inhibited the nitrilase reaction in a reversible,
      apparently competitive manner. A mutant nitrilase containing alanine or serine
      instead of Cys165, which is essential for nitrilase catalytic activity, showed no
      amidase activity. This observation demonstrated that Cys165 plays a crucial role
      in the hydrolysis of amides as well as nitriles. Together with some reports that
      certain nitrilases were previously noted to produce low amounts of amide as a by
      product from nitrile, the above unexpected findings suggested the existence of a
      common tetrahedral intermediate in the nitrilase reaction involving nitrile or
      amide as a substrate.

PMID- 9918785
TI  - DNA topoisomerase inhibitors induce reversible senescence in normal human
      fibroblasts.
AB  - Inhibitors of DNA topoisomerases I and II induced arrest in cell division in
      normal human fibroblasts depending on cell divisions. Arrested cells showed
      morphology similar to those of normally senesced cells and strongly induced
      senescence-associated beta-galactosidase. In these cells, p16ink4a was
      upregulated, whereas p21waf1 or p53 was not altered. Upon removal of the
      inhibitors, the cells resumed growth but their cumulative population doublings
      were reduced dose dependently. Accelerated telomere shortening was not observed
      in the arrested cells. These results suggest that DNA topoisomerase inhibitors
      are efficient and reversible inducers of premature senescence in normal human
      cells.

PMID- 9918786
TI  - Recombinant adenovirus expressing Von Hippel-Lindau-mediated cell cycle arrest is
      associated with the induction of cyclin-dependent kinase inhibitor p27Kip1.
AB  - A recombinant adenovirus containing the Von Hippel-Lindau (VHL) cDNA was
      constructed (AdVHL) and used to investigate the function of this tumor suppressor
      gene. Exposure of renal and breast cancer cell lines to AdVHL resulted in high
      levels of VHL mRNA and protein. AdVHL infection resulted in G1 cell cycle arrest
      and growth inhibition of renal and breast cancer cell lines. AdVHL-mediated cell
      cycle arrest was associated with induction of the cyclin-dependent kinase
      inhibitor (CDKI) p27Kip1 and inhibition of CDK2 and cyclinB1-dependent cdc2
      activities. Nuclear run-on analyses and actinomycin D inhibition studies indicate
      that the induction of p27Kip1 RNA by VHL is mediated at least in part through an
      increase in p27Kip1 mRNA synthesis. Furthermore, [35S]methionine pulse-chase
      studies indicate that the increase in p27Kip expression is also regulated through
      posttranscriptional control mechanisms. These studies support a novel concept
      that the tumor suppressor gene VHL controls cell cycle progression by regulation
      of p27Kip1 at both the mRNA and protein levels.

PMID- 9918787
TI  - Mutational analysis of two unstructured domains of the 5' untranslated region of
      HCV RNA.
AB  - Translation initiation of hepatitis C virus (HCV) RNA genome is mediated by an
      internal ribosome entry site (IRES). To further comprehend the mechanism of
      translation initiation of HCV RNA, we investigated the importance of two
      unstructured, highly conserved, single-stranded pyrimidine-rich sequences located
      immediately upstream of domain II (nt38-43) and between domains II and III (nt120
      125) in HCV translation. A series of defined mutations was engineered and
      introduced into a dicistronic vector in order to assess their impact on in vitro
      translation. Our data indicated that nucleotide sequence 38-43 is not essential
      for HCV translation. In contrast, mutational analysis of the second sequence
      motif (nt120-125) suggested that this region was important for maintaining the
      proper structure within the IRES element although the primary sequence itself was
      not critical for IRES function. More importantly, it appeared that mutations
      which allowed juxtaposition of neighboring bases (nt112-119) to the pseudoknot
      structure, were detrimental to translation initiation.

PMID- 9918788
TI  - Binding properties of the artificial zinc fingers coding gene Sint1.
AB  - On the basis of the recognition "code" that suggests specific rules between zinc
      finger's primary structure and the finger's potential DNA binding sites, we have
      constructed a new three-zinc finger coding gene to target the nine base pair DNA
      sequence: 5'-TGG-ATG-GAC-3'. This artificial gene named "Sint1" belongs to the
      Cys2-His2 zinc finger type. The amino acid positions, crucial for DNA binding,
      have been specifically chosen on the basis of the amino acid/base contacts more
      frequently represented in the available list of the proposed recognition "code".
      Here we demonstrate that Sint1 protein binds specifically the double strand
      "code" DNA target, with a dissociation constant (Kd) comparable to the Kd of the
      well known Zif268 protein. Sint1 "code" deduced and the "experimental" selected
      DNA binding sites share five nucleotide positions. Interestingly, Sint1 shows
      both high affinity and specificity toward the single strand "code" DNA binding
      site, with a Kd comparable to the corresponding double strand DNA target.
      Moreover, we prove that Sint1 is able to bind RNA similarly to several natural
      zinc finger proteins.

PMID- 9918789
TI  - Cellular prion proteins of mammalian species display an intrinsic partial
      proteinase K resistance.
AB  - Prion diseases are characterized by the intraneuronal accumulation of a
      pathological isoform (PrP(Sc)) of host-encoded prion protein (PrP(C)). While
      PrP(Sc) displays a partial resistance, PrP(C) is easily degraded by this enzyme.
      As it turned out in our experiments, PrP(C) of six species is initially degraded
      to an intermediate fragment of 25-28 kDa prior to complete proteolysis which was
      solely detected by antibodies binding to epitopes carboxy-terminally of amino
      acid 144 of PrP(C). The intermediate fragment thus lacked the aminoterminus of
      PrP(C). These findings are well in line with the putative structure of PrP(C):
      the amino-terminus consists of a highly flexible and thus more proteinase K
      sensitive tail while the carboxy-terminus is folded into possibly more resistant
      alpha-helices and beta-sheets. We observed significant differences in the PK
      sensitivities of PrP(C) from six different species and from three ovine PrP
      alleles, while no remarkable variation was seen in PrP(C) from six regions of an
      ovine brain. This indicates that variations in the sequence of PrP may alter its
      three-dimensional structure and consequently change its sensitivity towards
      proteolytic enzymes.

PMID- 9918790
TI  - Oxylipin formation in fungi: biotransformation of arachidonic acid to 3-hydroxy
      5,8-tetradecadienoic acid by Mucor genevensis.
AB  - The soil fungus Mucor genevensis was shown to convert exogenous arachidonic acid
      to the oxylipin 3-hydroxy-5Z,8Z-tetradecadienoic acid (3-HTDE) as determined by
      gas chromatography/mass spectrometry. This metabolite was only found in the
      aqueous supernatant together with free linoleic acid, but not in the final fungal
      biomass. In contrast, the corresponding primary arachidonic acid metabolite (3R)
      hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoic acid (3-HETE), which has been earlier
      shown to be produced by the yeast Dipodascopsis uninucleata, could not be
      detected. These observations may be plausibly explained by a retroconversion by
      M. genevensis of arachidonic acid to linoleic acid before the latter is
      metabolised to 3-HTDE.

PMID- 9918791
TI  - Molecular cloning and characterization of the mouse ceramide glucosyltransferase
      gene.
AB  - Ceramide glucosyltransferase (glucosylceramide synthase, GlcT-1, EC 2.4.1.80)
      catalyzes the first step in glycosphingolipid synthesis, the transfer of glucose
      from UDP-glucose to ceramide. The product, glucosylceramide, serves as a core
      structure for over 300 species of glycosphingolipids. The enzyme is a key
      regulatory factor controlling intracellular levels of ceramide and
      glycosphingolipids. We have cloned the gene for mouse ceramide
      glucosyltransferase, Ugcg. The gene spans approximately 32 kb and is composed of
      9 exons and 8 introns. The promoter region was found to lack TATA and CAAT boxes
      but contains Spl binding sites, which are indicators of typical housekeeping
      genes. In addition to these general transcription factor binding sites, the
      motifs for AhR, NF-kappaB, AP-2 and GATA-1 binding sites were found.

PMID- 9918792
TI  - Transcriptional repressors are increased in pancreatic islets of type 2 diabetic
      rats.
AB  - To further clarify the mechanism of impaired insulin gene transcription in the
      diabetic state, we investigated the expression and function of the
      transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM
      gene generates both transcriptional activators and repressors by alternative
      splicing and an intronic promoter. We isolated a novel alternatively spliced CREM
      isoform, CREM-17X, which efficiently represses insulin gene transcription, in
      addition to the three previously reported repressors. We also compared mRNA
      levels of insulin and the CREM repressors in pancreatic islets of Wistar and GK
      (Goto-Kakizaki) rats, the well-characterized spontaneous animal model of type 2
      diabetes. The CREM repressor levels are increased, and the expression of insulin
      mRNA is decreased in GK rats, suggesting that increased CREM repressor expression
      in pancreatic islets could contribute to the decreased insulin gene transcription
      that results in impaired insulin secretion in type 2 diabetes.

PMID- 9918793
TI  - Alteration of HERG current profile during the cardiac ventricular action
      potential, following a pore mutation.
AB  - HERG is believed to encode the major sub-unit of the cardiac 'rapid' delayed
      rectifier K channel (I(Kr)). Both I(Kr) and HERG exhibit marked inward
      rectification at positive membrane potentials due to rapid inactivation and this
      is thought to influence significantly the contribution of the current to cardiac
      action potential (AP) repolarisation. We investigated directly the role played by
      rapid inactivation, by measuring current activated by a ventricular AP waveform,
      from Chinese Hamster Ovary cells transfected with HERG cDNA with a point-mutation
      (S631A) in the pore region. Square command pulses elicited HERG-S631A current
      which increased progressively in magnitude with test potential up to +30/+40 mV
      (n=6). During test pulses to +40mV, HERG-S631A exhibited little inactivation
      compared to wildtype HERG. During an action potential command, WT-HERG current
      developed progressively during the AP plateau and slow repolarisation phase,
      showing maximal current between -30mV and -40 mV (n=10). In contrast, HERG-S631A
      current increased earlier during the AP plateau, with a maximal amplitude near
      +30mV (n=7). Current then declined as the AP proceeded, giving rise to a 'bow'-
      or 'inverted-U-' shaped current profile. A mathematical model with inactivation
      removed from the HERG current reproduced the I-V profile of HERG-S631A. These
      data provide a direct demonstration that rapid inactivation normally plays a
      critical role in determining both time-course and voltage dependence of
      HERG/I(Kr) -current during the cardiac ventricular AP.

PMID- 9918794
TI  - Kaposi's sarcoma-associated herpesvirus (KSHV) chemokine vMIP-II and human SDF
      1alpha inhibit signaling by KSHV G protein-coupled receptor.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two proteins that are
      similar to human CC chemokines and a G protein-coupled receptor (KSHV-GPCR) that
      is constitutively active. KSHV-GPCR binds a number of human CXC and CC
      chemokines. We showed that interferon gamma-inducible protein-10 (IP-10), a human
      CXC chemokine, inhibits KSHV-GPCR signaling (Geras-Raaka et al., J. Exp. Med.
      188, 405-408, 1998). Here we show that viral monocyte inflammatory protein-II
      (vMIP-II), one of the KSHV-encoded CC chemokines, and stromal cell-derived factor
      1alpha (SDF-1alpha), a human CXC chemokine that blocks infection by human
      immunodeficiency virus-type 1, inhibit KSHV-GPCR signaling also. If KSHV-GPCR
      signaling is involved in viral pathogenesis, then these chemokines may affect the
      course of Kaposi's sarcoma and primary effusion lymphoma.

PMID- 9918795
TI  - Gene cloning, RNA distribution, and functional expression of mCX3CR1, a mouse
      chemotactic receptor for the CX3C chemokine fractalkine.
AB  - Human fractalkine and its apparent murine counterpart neurotactin are the only
      members identified so far of the CX3C subfamily of chemokines. Recently, a human
      fractalkine receptor was identified and named CX3CR1. Here we have identified a
      mouse counterpart of this receptor. The receptor was identified by analysis of a
      mouse genomic clone named PC2 isolated by homology hybridization using CX3CR1 as
      probe. Clone PC2 has a 354-codon open reading frame that has 83% amino acid
      identity to CX3CR1. PC2 RNA was abundant in brain and lung and comparatively less
      abundant in lung, liver, kidney, testis, and peripheral blood leukocytes, a
      pattern similar to that found for CX3CR1. The recombinant fractalkine, but no
      other chemokines tested, induced chemotaxis and transient increases in [Ca2+]i in
      HEK 293 cells transfected with PC2, whereas untransfected cells did not respond.
      Furthermore, fractalkine bound specifically to the transfected cells (Kd=4 nM).
      Thus, fractalkine is a functional ligand for this receptor and we propose to name
      it mCX3CR1 for murine CX3C chemokine receptor 1.

PMID- 9918796
TI  - Gene transfer in vitro and in vivo with Epstein-Barr virus-based episomal vector
      results in markedly high transient expression in rodent cells.
AB  - The EBV-based plasmid vectors, which carry oriP and EBNA1 gene from EBV genome,
      can be retained in the nucleus and replicate in human cells. Rodent cells are not
      permissive for the EBV plasmids, in terms of the plasmid replication. However,
      the EBV vector facilitates not only the long term maintenance of the plasmid but
      also high level gene expression at a transient phase after transfection. It has
      not been elucidated if rodent cells show this high level transient expression. We
      demonstrate that rodent cells transfected with an EBV vector expressed a marker
      gene more intensively than those with a conventional plasmid vector did. The high
      marker gene expression was also seen in rat myocardium injected in vivo with the
      EBV plasmid. The present data indicate that the EBNA1-oriP system functions in
      "non-permissive" rodent cells at transient phase, and may require different
      cellular factor(s) for the transient expression and plasmid replication.

PMID- 9918797
TI  - Characterization and chromosomal mapping of the human gene for SFT, a stimulator
      of Fe transport.
AB  - Hemochromatosis is the most common genetic disorder known in man and results in
      progressive tissue deposition of iron leading to cirrhosis of the liver, hepatic
      carcinoma, congestive heart failure, endocrinopathies, and premature death. SFT
      (stimulator of Fe transport) is a newly discovered transport protein that
      facilitates uptake of iron. Recent studies have demonstrated that although SFT
      expression is reciprocally regulated in response to cellular iron levels, it is
      aberrantly upregulated in the liver of hemochromatosis patients, indicating that
      enhanced SFT expression contributes to the etiology of this disease. Here we
      report the molecular cloning and characterization of the human gene for SFT. FISH
      analysis maps the SFT gene to human chromosome 10q21. PCR analysis indicates 1000
      nucleotides of intervening intron sequence near the 3' end of the coding region
      for SFT. Based on DNA sequence analysis of the additional 5' untranslated region
      obtained from the genomic clone, SFT lacks known metal-regulated transcriptional
      or translational control elements. These studies provide the basis for future
      elucidation of the mechanisms that control SFT expression in order to discover
      how this regulation is lost in hemochromatosis.

PMID- 9918799
TI  - Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung
      fibroblasts.
AB  - Kinin B1 receptors are induced by various inflammatory mediators. The aim of the
      present study was to investigate the effect of the CXC chemokine IL-8 on kinin B1
      receptor expression in IMR-90 cells, by performing binding studies and Northern
      blot analysis of B1 receptor mRNA levels. We demonstrated here that the density
      of the kinin B1 receptors could be increased by the chemokine IL-8 in a
      concentration- and time-dependent manner. IL-8 also increased the kinin B1
      receptor mRNA level in IMR-90 cells. IL-8-induced B1 receptor expression could be
      totally abolished by pretreatment with the metabolic inhibitors. Furthermore,
      expression was markedly reduced by antibodies to human IL-1alpha. In conclusion,
      IL-8 increased the expression of kinin B1 receptors in IMR-90 cells and this
      effect is likely to be secondary to the production of IL-1beta.

PMID- 9918798
TI  - Cloning and characterization of a novel transforming growth factor-beta1-induced
      TIAF1 protein that inhibits tumor necrosis factor cytotoxicity.
AB  - To determine how TGF-beta1 protects L929 fibroblasts against TNF-alpha
      cytotoxicity, we report the isolation and characterization of a novel cDNA
      encoding a 12-kDa TGF-beta1-induced antiapoptotic factor, designated TIAF1. GFP
      tagged TIAF1 protein is present mostly in perinuclear and nuclear locations.
      TIAF1 inhibits the cytotoxic effects of TNF-alpha and overexpressed TNF receptor
      adaptors TRADD, FADD, and RIP. L929 stable transfectants expressing TIAF1 do not
      have significant changes in the expression of TNF receptors and effector or
      regulatory proteins in apoptosis, which may account for the acquired TNF
      resistance in these cells. Notably, these cells have a significantly suppressed
      IkappaB-alpha protein expression, and IkappaB-alpha degradation is blocked when
      exposing these cells to TNF-alpha. Similarly, stimulation of untransfected L929
      cells with TGF-beta1 results in suppression of IkappaB-alpha expression and
      retarded IkappaB-alpha degradation in response to TNF-alpha. Despite the fact
      that the mechanism for blocking TNF cytotoxicity is unknown, TIAF1 is apparently
      involved in TGF-beta1 inhibition of IkappaB-alpha expression and suppression of
      TNF-mediated IkappaB-alpha degradation.

PMID- 9918800
TI  - Expression of rat interleukin-5 and generation of neutralizing antiserum: a
      comparative study of rat IL-5 produced in Escherichia coli and insect cells.
AB  - A cDNA coding for rat IL-5 was obtained by RT-PCR from total spleen RNA. With the
      exception of a single a.a. replacement at position 85 (L-P), it is identical to
      the published sequence obtained by retroviral gene transfer. This cDNA was used
      to express biologically active recombinant IL-5 in E. coli and in insect cells
      using a baculovirus system. Rat IL-5 is more active on B13, an IL-5 dependent
      cell line, when produced in insect cells (specific activity 1.47 x 10(11)UI/mg
      compared to 4.28 x 10(6)UI/mg). This increased activity seems to be associated
      with the presence of IL-5 homodimers in recombinant protein preparations. A
      rabbit antiserum raised against recombinant bacterial IL-5 specifically inhibited
      B13 proliferation induced by bacterial and baculoviral IL-5. The availability of
      such reagents should facilitate studying the role of IL-5 in different infectious
      diseases, experimental allergic encephalomyelitis and in transplantation biology
      where the rat represents a more suitable model than mice.

PMID- 9918801
TI  - Molecular interactions within the melanogenic complex: formation of heterodimers
      of tyrosinase and TRP1 from B16 mouse melanoma.
AB  - Melanin synthesis in mammals is catalyzed by three structurally related, membrane
      bound proteins, tyrosinase, and the tyrosinase-related proteins 1 and 2 (TRP1 and
      TRP2). Current evidence suggests that in vivo these proteins may form a
      multienzyme complex. However, neither the precise composition of the complex, nor
      the specific interactions between its components have been characterized. This
      study used purified preparations of tyrosinase and TRP1 to analyze their
      interactions in non ionic detergent solution. Purified tyrosinase and TRP1
      behaved as homodimers as judged by gel filtration chromatography and
      electrophoresis. Upon mixing of the purified proteins, the preferential formation
      of heterodimers was detected by: i) coelution in gel filtration chromatography
      with a shift to a common partition coefficient for both proteins, and ii) the
      occurrence of fluorescent energy transfer between fluorescein-labeled tyrosinase
      and rhodamine-labeled TRP1. However, the formation of heterodimers did not cause
      changes in the tyrosine hydroxylase activity of the enzymes, at least under
      standard assay conditions. Thus, tyrosinase and TRP1 interact strongly and
      specifically in detergent solution to form an heterodimer that might contribute
      to the formation of the melanogenic complex.

PMID- 9918802
TI  - Cerebellar granule cell GABA(A) receptors studied at the single-channel level:
      modulation by protein kinase G.
AB  - Rat cerebellar granule cells GABA(A) receptors were studied at the single-channel
      level in outside-out patches. Three conductance levels were detected as activated
      by 0.1 microM GABA: 11, 20 and 30 pS. Single-channel I-V relationships were
      linear. The probability of opening did not vary over time within single patches.
      Kinetic analysis brought to a mean open time constant of 3.2, 2.9 and 2.8 ms
      respectively for each conductance level and a closed time histogram fitted by the
      sum of two exponential functions (tau c1 = 2.1 ms, 43%; tau c2 = 18.2 ms, 57%).
      Protein kinase G (PKG) activation did not affect single-channel conductances, but
      resulted in a reduction over time of single-channel open probability for all the
      conductance levels. Kinetically, protein kinase G modified the mean open time
      constants and the relative areas of the two components of the closed state
      distribution whereas the mean closed time constants remained unaffected. These
      results confirm and add details about cerebellar granule GABA(A) receptors down
      regulation by PKG.

PMID- 9918803
TI  - Growth hormone-dependent tyrosine phosphorylation of a GH receptor-associated
      high molecular WEIGHT protein immunologically related to JAK2.
AB  - A critical step in growth hormone (GH) signalling is the GH-induced activation of
      the GH receptor (GHR)-associated tyrosine kinase, JAK2. JAK2 is a 120 kD member
      of the Janus family of tyrosine kinases, whose other mammalian members include
      JAK1, JAK3, and TYK2. Using 3T3-F442A murine preadipocytes, we now report
      detection of a Mr approximately 170 kD protein, referred to as HMW ("high
      molecular weight") JAK2, that is specifically reactive in immunoprecipitation and
      immunoblotting experiments with three independently-derived anti-JAK2 antibodies-
      two directed at carboxyl-terminal regions of the molecule and one directed at the
      amino-terminus. Like JAK2, HMW JAK2 is tyrosine phosphorylated in response to GH
      treatment of cells and is coimmunoprecipitated with anti-GHR serum. Thus, HMW
      JAK2 is a protein not heretofore described that is immunologically related to
      JAK2 and is physically and functionally associated with the GHR.

PMID- 9918804
TI  - Smad3 is involved in the intracellular signaling pathways that mediate the
      inhibitory effects of transforming growth factor-beta on StAR expression.
AB  - Transforming growth factor betas (TGFbetas) constitute a family of dimeric
      proteins that regulate growth and differentiation of many cell types. TGFbeta1 is
      also a potent autocrine regulator of adrenocortical steroidogenesis. We have
      recently shown that in primary cultures of bovine fasciculo-reticularis cells,
      the main target of TGFbeta is the steroidogenic acute relay protein (StAR), a key
      protein necessary for intramitochondrial cholesterol transport. Here, we show
      that StAR expression is also inhibited by TGFbeta1 in the human adrenocortical
      carcinoma cell line NCI-H295R. This inhibitory effect is mediated by Smad
      proteins. Indeed, we found that overexpression of wild-type Smad3 inhibited
      endogenous StAR mRNA expression while overexpression of a dominant negative Smad3
      protein reversed the inhibitory effect of TGFbeta1 on StAR mRNA expression. Taken
      together, these results demonstrate that the Smad3 protein is involved in TGFbeta
      dependent regulation of steroidogenesis.

PMID- 9918805
TI  - Identification of two uridine binding domain peptides of the UDP-glucose-binding
      site of rabbit muscle glycogenin.
AB  - Glycogenin, the autoglucosyltransferase that initiates the de novo biosynthesis
      of glycogen, photoaffinity labeled with [beta32P]5-azido-UDP-glucose. The
      photoinsertion of the azidouridine derivative showed activating ultraviolet light
      dependency, saturation effects, and inhibition by UDP-glucose, thus demonstrating
      the specificity of the interaction. In the absence of Mn2+, the requirement for
      the catalytic activity of glycogenin, the photolabeling decreased by 70%.
      Competitive binding experiments indicated that the pyrophosphate or a phosphate
      was the moiety of UDP-glucose implicated in the strongest interaction at the
      binding site. Proteolytic digestion of photolabeled glycogenin resulted in the
      identification of two labeled fragments, 89-143 and 168-233, that carried the
      uridine binding sites. This is the first report of the region of glycogenin that
      harbors the UDP-glucose-binding domain.

PMID- 9918806
TI  - Potential role of the JNK/SAPK signal transduction pathway in the induction of
      iNOS by TNF-alpha.
AB  - Nitric oxide production by macrophages is principally regulated by the calcium
      independent enzyme, inducible nitric oxide synthase (iNOS). Both
      lipopolysaccharide and TNF-alpha synergize with IFN-gamma in the expression of
      iNOS with subsequent production of nitric oxide. Previous work has shown that IL
      4 downregulates iNOS and nitric oxide expression by macrophages stimulated with
      LPS and IFN-gamma. In this study, we found that IL-4 also downregulated iNOS and
      nitric oxide expression induced by IFN-gamma and TNF-alpha and in mouse
      macrophages. Because various members of the mitogen-activated protein kinases and
      their upstream kinases have been shown to directly or indirectly activate a
      number of transcription factors including AP-1 and NFkappaB, we examined the
      effects of IL-4 on TNF-alpha activation of the MAPKs. Our results show that IL-4
      modestly inhibited JNK/SAPK and ERK activation by TNF-alpha. Previously, we
      showed that selective pharmacologic inhibition of the ERK and/or p38mapk pathway
      did not affect NO2- expression. Treatment of cells with the chloride channel
      blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) showed a dose
      response inhibition of NO2- expression. NPPB was also found to inhibit ERK and
      JNK/SAPK activation but not p38mapk with TNF-alpha stimulation. The discordance
      between the marked degree of inhibition of iNOS transcript by IL-4 and the modest
      inhibition of JNK/SAPK and ERK suggests that the mechanism by which IL-4 inhibits
      iNOS transcription appears more complex than a mere inhibition of these MAPKs.

PMID- 9918807
TI  - Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine
      phosphorylase.
AB  - The angiogenic factor platelet-derived endothelial cell growth factor/thymidine
      phosphorylase (PD-ECGF/TP) is expressed at higher levels in a wide variety of
      solid tumors compared to adjacent normal tissues. Patients with PD-ECGF/TP
      positive colon and esophageal tumors have a poorer prognosis than those with
      negative tumors. The expression of PD-ECGF/TP is a prognostic factor independent
      of microvessel density suggesting that TP has effects on tumor progression
      independent of its angiogenic activity. Evidence that hypoxia and apoptosis
      affect tumor growth prompted us to determine whether increased expression of PD
      ECGF/TP prevents apoptosis induced by hypoxia. KB/TP cells transfected with a PD
      ECGF/TP cDNA were resistant to hypoxia-induced apoptosis. Among the degradation
      products of thymidine produced by PD-ECGF/TP, 2-deoxy-D-ribose and thymine
      partially prevented hypoxia-induced apoptosis. The ability of 1 microM 2-deoxy-D
      ribose in combination with the same concentration of thymine to prevent hypoxia
      induced apoptosis was similar to that of the overexpressed TP in KB cells. A
      concentration of 1 microM 2-deoxy-L-ribose abrogated the effects of these
      degradation products of thymidine. These findings suggested that TP can confer
      resistance to apoptosis induced by hypoxia and the degradation products of
      thymidine are involved in this resistance. Expression of PD-ECGF/TP may play an
      important role in the progression of solid tumors, and inhibitors of TP and
      analogs of the degradation products of thymidine may suppress the growth of
      tumors by promoting apoptosis.

PMID- 9918808
TI  - The simian virus 40 core C enhancer-like element is a positive regulator in the
      rat alpha1B adrenergic receptor gene proximal promoter.
AB  - Transcription of the rat alpha1B adrenergic receptor (alpha1B AR) gene is
      controlled by three promoters (P1, P2, and P3), which generate 2.3-, 2.7-, and
      3.3-kb transcripts, respectively. The expression of the 2.3-kb mRNA species is
      tissue-specific. To explore the underlying mechanism, the P1 promoter was
      analyzed. DNase I footprinting of the P1 promoter yielded three protected
      regions: Plfl(-49 to -62); P1f2 (-73 to -90), and P1f3 (-95 to -115). Sequence
      analysis of P1f3 revealed the presence of an SV40 core C enhancer-like element.
      In gel mobility shift assays, P1f3 was found to bind a sequence specific protein,
      which was competed away by a SV40 core C enhancer consensus oligonucleotide.
      Mutations of this enhancer-like core sequence within P1f3 significantly reduced
      specific protein binding to P1f3 and inhibited P1 promoter activity. The
      distribution of the protein which binds to P1f3 is restricted. These findings
      suggest that the P1 promoter is controlled by a cell-type-specific transcription
      factor, which may account for the tissue-specific expression of 2.3-kb rat
      alpha1B AR mRNA species.

PMID- 9918809
TI  - Polymorphism and disorder of poly(dA).poly(dT) in fibers.
AB  - The absence of proportionality between fiber length and interbase axial distance
      reveals a high degree of disorder in fibers of poly(dA).poly(dT) when the
      relative humidity (r.h.) varies. According to X-ray patterns, the increase of
      fiber length does not correspond to any conformational change. The B' structure
      is present alone and in a better-organized form at higher r.h. We noted a
      dependence of length values on the direction of variation of the r.h. An unusual
      minimum of fiber length is observed around 65% r.h. and explained as been due to
      an amorphous part of the fiber, essentially composed of single strands of
      poly(dA) and poly(dT). At a temperature higher than 30 degrees C, the transition
      B'(alpha)-B* takes place but is associated with an important decrease of fiber
      length in spite of constancy of the helical rise per base pair. It is shown that
      this behavior is also due to the amorphous part of the fiber and not to a
      conformational transition.

PMID- 9918810
TI  - Expression of peroxisome proliferator activated receptor mRNA in normal and
      tumorigenic rodent mammary glands.
AB  - The peroxisome proliferator activated receptors (PPARs) alpha, beta/delta, and
      gamma are novel nuclear hormone receptors activated by long chain fatty acids and
      synthetic ligands and which regulate lipid metabolism. Recent studies have
      detected PPARgamma mRNA in human mammary tumor cell lines. The current study
      examined the expression profile of PPAR mRNAs in normal and malignant rodent
      mammary tissues. Virgin murine mammary glands contained PPAR alpha, beta/delta,
      and gamma mRNAs based on northern blot analysis. The PPARgamma isoform was
      predominantly gamma2 based on quantitative PCR analysis. During pregnancy and
      lactation, the PPARalpha and gamma mRNAs decreased while the PPAR beta/delta mRNA
      remained relatively unchanged. NMuMG cells, an epithelial line derived from
      normal murine mammary gland, expressed PPAR alpha, beta/delta, and gamma mRNAs,
      independent of the presence or absence of compounds modifying PPAR activity. In
      rats, the physiologic expression pattern of PPARgamma mRNA paralleled the murine
      model; levels were detected in virgin but not lactating mammary glands. In
      addition, the PPARgamma mRNA was not detected in several histologically distinct
      7,12-dimethylbenz(a)anthracene induced mammary tumors. These findings suggest
      that PPARs may regulate mammary epithelial and stromal cell function in response
      to physiologic or pathologic stimuli that profoundly alter lipid metabolism.

PMID- 9918811
TI  - Inducibility of BDNF gene promoter I detected by calcium-phosphate-mediated DNA
      transfection is confined to neuronal but not to glial cells.
AB  - Although DNA transfection with calcium-phosphate/DNA precipitates for promoter
      analysis of genes has been previously applied to primary cultures of neuronal
      cells, it remains uncertain whether the expression of the introduced genes in
      glial cells, which are also in primary culture, affects the transcriptional
      signals obtained. Using plasmid DNA containing the brain-derived neurotrophic
      factor (BDNF) gene promoter I or c-fos promoter, we investigated the optimum
      conditions for calcium-phosphate-mediated DNA transfection in primary culture of
      rat cortical neuronal cells. Normalizing the firefly luciferase activity of the
      experimental reporter gene to the Renilla luciferase activity of the internal
      control increased experimental reliability. Maximum expression of firefly
      luciferase activity in the cells stimulated by membrane depolarization required 6
      12 hrs of incubation after stimulation. Differences in the ratio of the
      experimental reporter gene to the internal control did not affect experimental
      gene expression. Under our optimal conditions, the activation of the BDNF gene
      promoter I was detected in neuronal but not in glial cells. Calcium-phosphate
      mediated DNA transfection should be widely applicable for promoter analysis of
      inducible genes in neurons.

PMID- 9918812
TI  - Na+,K+-ATPase was found to be the membrane component responsible for the
      hydrophobic behavior of the brain membrane tubulin.
AB  - We have previously described that the tubulin isolated from brain membranes as a
      hydrophobic compound by partitioning into Triton X-114 is a peripheral membrane
      protein [corrected]. The hydrophobic behavior of this tubulin is due to its
      interaction with membrane protein(s) and the interaction occurs principally with
      the acetylated tubulin isotype. In the present work we identified the membrane
      protein that interacts with tubulin as the Na+,K+-ATPase alpha subunit by amino
      acid sequencing. Using purified brain Na+,K+-ATPase we were able to isolate part
      of the total hydrophilic tubulin as a hydrophobic compound which contains a high
      proportion of the acetylated tubulin isotype.

PMID- 9918813
TI  - Identification of genes differentially expressed in vascular smooth muscle cells
      following benzo[a]pyrene challenge: implications for chemical atherogenesis.
AB  - We have previously shown that serial passage of vascular smooth muscle cells
      (vSMCs) treated with a single low dose of benzo[a]pyrene (BaP) induces
      acquisition of highly proliferative (i.e. atherogenic) phenotypes. To define the
      molecular basis of this response, differential display polymerase chain reaction
      was used to identify early target genes in murine vSMCs challenged with 3 microM
      BaP for 8 hr. Of 170 differentially expressed cDNAs, 111 were re-amplified, and
      64 examined for homology to known genes. Aac11 apoptosis inhibitor, aldose
      reductase, GalNAc transferase, TCP-1 chaperonin gene, and mouse mitochondrial
      gene, were downregulated in vSMCs treated with BaP. In contrast, enhanced
      expression of unique retrotransposon cDNAs were found in BaP-treated cells. This
      is the first report showing that BaP modulates the expression of these genes in
      mammalian cells. Of particular interest is the modulation of retrotransposon
      mRNAs which coupled to other genetic events, may play a significant role in the
      atherogenic response to this carcinogen.

PMID- 9918814
TI  - Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in
      rat Kupffer cells.
AB  - BACKGROUND AND AIMS: Treatment with acetaldehyde dehydrogenase inhibitors leads
      to increased liver acetaldehyde levels and prevents hepatic inflammation and
      necrosis in ethanol-fed rats. This is accompanied by IkappaBa preservation and
      decreased activation of nuclear factor (NF)-kappaB. The present in vitro study
      was aimed to clarify whether acetaldehyde has an effect on degradation of
      IkappaBalpha and activation of NF-kappaB in LPS-stimulated rat Kupffer cells.
      METHODS: Kupffer cells were isolated from male Sprague-Dawley rats and
      preincubated with various concentrations of acetaldehyde (25-100 microM).
      Thereafter the cells were stimulated with LPS, and cytosolic and nuclear
      fractions were prepared. IkappaBalpha and p65 proteins and activation of NF
      kappaB were evaluated. RESULTS: In LPS-stimulated rat Kupffer cells, acetaldehyde
      diminished proteolytic degradation of IkappaBalpha, inhibited nuclear
      translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF
      kappaB activation. CONCLUSIONS: Acetaldehyde is clearly involved in the
      stabilization of IkappaBalpha protein and suppression of NF-kappaB activation in
      rat Kupffer cells. Acetaldehyde may form an adduct with IkappaBalpha, thus making
      the protein less susceptible to degradation.

PMID- 9918815
TI  - Enzymatically active papain preferentially induces an allergic response in mice.
AB  - Human exposure to papain, a cysteine proteinase, is associated with
      hypersensitivity reactions. We demonstrate in mice that enzymatically active
      papain preferentially induces an IgG1 response and results in mast cell
      degranulation, both features typical of an allergic reaction. Inactive papain,
      blocked with E-64, appears to desensitize mice to subsequent challenge by active
      enzyme. These results suggest that the enzymatic activity of papain is critical
      in inducing an allergic response and that the use of inactive allergens may be a
      possible strategy for desensitizing allergic individuals.

PMID- 9918816
TI  - Serum leptin levels do not rise during pregnancy in age-matched rats.
AB  - The serum leptin profile and its production in adipose tissue during pregnancy
      and lactation were investigated along with changes in appetite and factors
      reflecting nutritional status in 11-week-old rats. Serum leptin levels in
      pregnant rats were stable except on day 20 of pregnancy and significantly reduced
      during lactation compared to nonpregnant rats (P < 0.001). Circulating leptin
      levels corresponded with changes in appetite during pregnancy and
      postparturition. Leptin mRNA in parametrial adipose tissue reflected the
      circulating levels, also being significantly reduced during late pregnancy and
      during lactation (P < 0.05). Leptin mRNA expression was observed in placenta, but
      the amount suggested little influence on circulating leptin levels. These results
      indicate that reduction in leptin mRNA in parametrial adipose tissue and
      circulating leptin levels may increase appetite during late pregnancy and
      lactation and may play a role in regulating metabolic homeostasis around
      parturition in rats.

PMID- 9918817
TI  - Autoxidation rates of neuronal nitric oxide synthase: effects of the substrates,
      inhibitors, and modulators.
AB  - Autoxidation rates of the full-length neuronal nitric oxide synthase (nNOS) were
      analyzed and found to be composed of three phases, 60 s(-1) (28%), 5.5 s(-1)
      (11%) and 0.048 s(-1) (61%). Addition of L-Arg, N(G)-hydroxy-L-Arg (NHA), and
      N(G)-monomethyl-L-Arg markedly decreased the rate constants for the first and
      second phases down to 12-20 s(-1) and 0.32-2.6 s(-1), respectively. Addition of
      (6R)-5,6,7,8-tetrahydro-L-biopterin (H4B) increased the amplitude of the second
      phase up to 29% of the total. Addition of NHA decreased the rate of the first
      phase by 4.4-fold in the presence of H4B, whereas addition of L-Arg and other
      modulators did not significantly affect the rates under the same conditions.
      Thus, we deduce that (1) L-Arg stabilizes the O2-bound ferrous complex for
      efficient O-O bond cleavage to occur; (2) H4B influences the O2-bound ferrous
      complex in a fashion different from L-Arg; and (3) NHA induces a characteristic
      distal-site structure in the presence of H4B, reflecting a difference in the
      mechanism of activation of O2 in the first step (monooxygenation of L-Arg) and
      the second step (monooxygenation of NHA).

PMID- 9918818
TI  - Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine
      D1 receptor binding in the suprachiasmatic nuclei.
AB  - The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1
      receptor systems in the central nervous system, mainly in the suprachiasmatic
      nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy.
      125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day
      21) was transferred in considerable amount into the fetal circulation. In vitro
      autoradiography data demonstrated an increase in the melatonin binding activity
      in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused
      by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN
      was then normalized after the melatonin system of the neonate started to work.
      The pregnant rats themselves did not show such a change in their melatonin
      receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was
      affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as
      well as in that of mothers. These results clearly indicate that the fetal
      circadian clock in the SCN is controlled and prepared before birth to some extent
      by maternal melatonin rhythm.

PMID- 9918819
TI  - Disruption of c-Fos leads to increased expression of NAD(P)H:quinone
      oxidoreductase1 and glutathione S-transferase.
AB  - Regulation of the basal and induced expression of detoxifying enzymes such as
      NAD(P)H:quinone oxidoreductasel (NQO1) and glutathione S-transferase (GST) by the
      antioxidant response element (ARE) is important for cellular protection against
      oxidative stress. The ARE contains AP1 and AP1-like elements and is known to bind
      to several leucine zipper proteins including c-Fos. Previous studies (Venugopal,
      R., and Jaiswal, A.K. (1996) Proc. NatL Acad. Sci. USA 93, 14960-14965) have
      shown that overexpression of c-Fos in transfected cells leads to repression of
      ARE-mediated gene expression. In the present report, we used c-Fos-/- mice and
      investigated the physiological (in vivo) role of c-Fos in repression of the NQO1
      and GST genes expression. The analysis of enzyme activity levels showed
      significant increases in NQO1 and GST activities in several tissues of c-Fos-/-
      mice, as compared with wild type (c-Fos+/+) mice. The increases in enzyme
      activities were supported by Wetern analysis of respective proteins. Western
      analyses showed significant increases in the expression of NQO1 in kidney, liver
      and skin tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+)
      controls. Western analyses also demonstrated an increased expression of the GST
      Ya gene in kidney and liver tissues of the c-Fos-/-mice. These results confirm a
      negative (repressive) role for c-Fos in the expression of NQO1, GST Ya, and other
      detoxifying enzyme genes.

PMID- 9918820
TI  - Resveratrol stimulates the proliferation and differentiation of osteoblastic
      MC3T3-E1 cells.
AB  - Nutritional and pharmacological factors are needed to prevent bone loss that
      occurs with increasing age. The chemical compounds that act on bone metabolism as
      nutrients in food, however, are poorly understood. The effect of resveratrol, a
      natural phytoestrogen, on the proliferation and differentiation of osteoblastic
      MC3T3-E1 cells was studied. Resveratrol dose-dependently increased DNA synthesis
      (10(-9)-10(-7) M) of MC3T3-E1 cells. In addition, resveratrol increased alkaline
      phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (10(
      6)-10(-5) M). Moreover, the antiestrogen tamoxifen eliminated the stimulation of
      MC3T3-E1 cells on the proliferation and ALP activity by resveratrol. On the other
      hand, resveratrol inhibited prostaglandin E2 production in MC3T3-E1 cells (10(-8)
      10(-6) M). Our present study is the first to demonstrate that resveratrol
      directly stimulates cell proliferation and differentiation of osteoblasts.

PMID- 9918821
TI  - Prolongation of the p53 response to DNA strand breaks in cells depleted of PARP
      by antisense RNA expression.
AB  - The observation that 3-aminobenzamide, which inhibits a variety of ADP-ribose
      transferases, prolongs the gamma-irradiation-induced increase in intracellular
      p53 concentration suggested that one or more of such enzymes may determine the
      duration of the p53 response during G1 arrest. The role of poly(ADP-ribose)
      polymerase (PARP), an abundant nuclear enzyme activated by DNA strand breaks, in
      the p53 response to y-irradiation was investigated in Burkitt's lymphoma AG876
      cells stably transfected with an inducible PARP antisense construct. Immunoblot
      analysis revealed that the cellular content of PARP was reduced to virtually
      undetectable levels after incubation of transfected cells for 72 h with the
      inducer dexamethasone. In noninduced antisense cells, the p53 concentration
      reached a maximum 2 h after exposure to 6.3 Gy of gamma-radiation and returned to
      control values by 4 h. In contrast, the p53 response in PARP-depleted antisense
      cells peaked at 4 h, with the levels of p53 remaining elevated for up to 12 h
      after y-irradiation. The maximal increase in p53 concentration was similar in
      both induced and noninduced cells. These results thus indicate that PARP
      activity, in part, determines the duration, but not the magnitude, of the p53
      response to DNA damage.

PMID- 9918822
TI  - Dynamic recycling of ERGIC53 between the endoplasmic reticulum and the Golgi
      complex is disrupted by nordihydroguaiaretic acid.
AB  - Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, has recently been
      demonstrated to block protein transport from the endoplasmic reticulum (ER) to
      the Golgi complex. The ER to Golgi transport is primarily operated by the ER
      Golgi intermediate compartment (ERGIC). We examined the effect of NDGA on the
      ERGIC, focusing on the distribution of its marker ERGIC53. In control cells
      ERGIC53 was distributed to vesicular tubular structures corresponding to the
      ERGIC as well as to the ER and the cis-Golgi, reflecting its cycling between
      these compartments. Upon treatment of cells with NDGA, ERGIC53 was rapidly
      accumulated in the Golgi and undetectable in the ER and the ERGIC. Prolonged
      incubation of cells with the drug, however, caused redistribution of ERGIC53 and
      resident Golgi proteins to the ER. Thus, it is likely that NDGA has dual effects
      on ERGIC53 cycling; the initial accumulation in the Golgi may be caused by
      blocking its retrieval from the cis-Golgi to the ER/ERGIC, while the delayed
      redistribution to the ER may occur through a pathway induced by the drug that is
      different from the COPI-dependent pathway.

PMID- 9918823
TI  - A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong
      anti-HIV peptide T140.
AB  - T22 ([Tyr5,12, Lys7]-polyphemusin II) is an 18-residue peptide amide, which has
      strong anti-HIV activity. T22 inhibits the T cell line-tropic (T-tropic) HIV-1
      infection through its specific binding to a chemokine receptor CXCR4, which
      serves as a coreceptor for the entry of T-tropic HIV-1 strains. Herein, we report
      our finding of novel 14-residue CXCR4 inhibitors, T134 and T140, on the basis of
      the T22 structure. In the assays we examined, T140 showed the highest inhibitory
      activity against HIV-1 entry and the strongest inhibitory effect on the binding
      of an anti-CXCR4 monoclonal antibody (12G5) to CXCR4 among all the CXCR4
      inhibitors that have been reported up to now.

PMID- 9918824
TI  - Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid
      differentiation.
AB  - Butyric acid (BA) is known to induce overexpression of fetal hemoglobin and then
      erythroid differentiation. Therefore, BA is currently under clinical
      investigation as a potential therapy for the treatment of sickle cell disease and
      cancer. Nevertheless, the molecular mechanisms involved in BA-induced
      differentiation remain largely unknown. Previous reports have shown that BA
      induced overexpression of erythroid genes occurred at the transcriptional level,
      suggesting the involvement of erythroid transcription factors. Here, we intend to
      demonstrate the requirement of GATA-1 and NF-E2 transcription factors in the BA
      induced erythroid differentiation of human leukemic K562 cells. Time-course
      experiments showed that nuclear levels of GATA-1 and p45 NF-E2 proteins increased
      during BA treatment. Moreover, antisense oligodeoxynucleotides targeting either
      GATA-1 or p45 NF-E2 proteins inhibited both protein expression and BA-induced
      differentiation. In contrast, BA-induced cell growth inhibition was not affected.
      These results provide the first direct evidence for the requirement of GATA-1 and
      NF-E2 in BA-induced differentiation process.

PMID- 9918825
TI  - Insulin resistance in cancer patients is associated with enhanced tumor necrosis
      factor-alpha expression in skeletal muscle.
AB  - The roles of tumor necrosis factor (TNF)-alpha and the facilitative glucose
      transporter (GLUT) 4 on the induction of insulin resistance in peripheral tissues
      of cancer patients was examined by quantitative competitive PCR on biopsies of
      abdominal rectal muscle from patients with gastrointestinal cancer. The degree of
      insulin resistance in these patients was measured by the euglycemic
      hyperinsulinemic glucose clamp using a high physiologic insulin concentration
      (100 microU/ml). Quantitative competitive PCR was carried out using DNA
      competitors constructed by deleting 20-30 bp between the two primer annealing
      sites. Decreased glucose uptake (M value) in peripheral tissues was accompanied
      by a significantly increased TNF-alpha mRNA in skeletal muscle (r=0.867,
      p=0.0025). GLUT4 mRNA, however, was positively correlated with M values (r=0.739,
      p=0.015). The amounts of mRNAs for TNF-alpha and GLUT4 in skeletal muscle were
      not correlated. Serum TNF-alpha concentrations remained below the limit of
      detection. These findings suggest that the insulin resistance in peripheral
      tissues of cancer patients is in part due to the induction TNF-alpha mRNA and the
      down regulation of GLUT4 mRNA in peripheral tissues.

PMID- 9918826
TI  - Glutathione and catalase provide overlapping defenses for protection against
      hydrogen peroxide in the yeast Saccharomyces cerevisiae.
AB  - Glutathione (GSH) is an abundant and ubiquitous low-molecular-weight thiol which
      has proposed roles in many cellular processes including protection against the
      deleterious effects of reactive oxygen species. Our experiments have addressed
      the role of GSH in protection against hydrogen peroxide in the yeast
      Saccharomyces cerevisiae, and have shown that GSH and catalase provide
      overlapping defense systems. GSH appears to be the primary antioxidant for
      protection against hydrogen peroxide since mutants lacking GSH (gsh1) or
      glutathione reductase (glr1) are sensitive, whereas, strains lacking catalase A
      (cta1) or catalase T (ctt1) are unaffected in resistance to this oxidant.
      Furthermore, following treatment with hydrogen peroxide, the levels of oxidized,
      protein-bound and extracellular GSH were all increased at the expense of
      intracellular GSH. However, there are two lines of evidence that indicate
      catalases are required in the absence of GSH; firstly, strains that lack both
      catalase A and T accumulate increased levels of oxidized glutathione following
      treatment with hydrogen peroxide; and secondly, deletion of catalase genes
      exacerbates the hydrogen peroxide sensitivity of glr1 and gsh1 mutants.

PMID- 9918827
TI  - Umbilical arterial S-nitrosothiols in stressed newborns: role in perinatal
      circulatory transition.
AB  - S-Nitrosothiols are potent endogenous vasodilators recently found to be in
      greater concentrations in fetal umbilical venous than arterial blood. We
      hypothesized that neonatal increases in SNOs may be involved in the normal human
      perinatal circulatory transition. Paired human umbilical artery and vein plasma
      samples were collected after birth. S-Nitrosothiol concentrations were measured
      as NO after photolysis--and NO3- after reduction in vanadium chloride--by
      chemiluminescence. Normal umbilical arterial serum SNO levels were nearly twice
      those of matched venous samples but were low in infants who did not transition
      normally to neonatal circulation. There was no difference in the concentration of
      NO3- between the normal and depressed infants. The parallel failure of some
      fetuses to switch both to a normal arteriovenous SNO relationship and a normal
      clinical post-partum state suggests that SNOs may be involved in the perinatal
      circulatory transition.

PMID- 9918829
TI  - Synthetic peptides corresponding to the beta-hairpin loop of rabbit defensin NP-2
      show antimicrobial activity.
AB  - Mammalian defensins, a class of antibacterial peptides, are composed of 29-35
      amino acids with six cysteines which form three disulfide bonds. Structural
      studies indicate a triple stranded beta-sheet structure with a well defined beta
      hairpin loop at the C-terminal region. It is demonstrated in this report that 18
      and 26 residue synthetic peptides corresponding to the beta-hairpin region,
      constrained by a single disulfide bond, have potent antimicrobial activity
      without hemolytic activity. Circular dichroism spectroscopy indicates that the
      single S-S bridge appears to constrain the peptides to a beta-structure. Peptides
      corresponding to the beta-hairpin region of defensins could thus be attractive
      candidates as therapeutic agents as well as good model compounds for
      investigation of the various physiological actions of defensins.

PMID- 9918830
TI  - Real-time visualization of PH domain-dependent translocation of phospholipase C
      delta1 in renal epithelial cells (MDCK): response to hypo-osmotic stress.
AB  - Green fluorescent protein (GFP)-tagged phospholipase C (PLC)-delta1 and its
      mutants were expressed in Madin-Darby canine kidney (MDCK) cells. GFP-PLC-delta1
      or the GFP-tagged pleckstrin homology (PH) domain of PLC-delta1 itself was found
      to be predominantly localized at the plasma membrane. The DeltaPH mutant or a
      site-directed mutant containing a PH domain which does not bind inositol 1,4, 5
      trisphosphate and cannot hydrolyze phosphatidylinositol 4, 5-bisphosphate in
      vitro was seen only in the cytosol. In living MDCK cells hypo-osmotic stress
      caused a rapid dissociation of GFP-PLC-delta1 from the plasma membrane, which
      coincided with phosphoinositide breakdown. A PLC inhibitor, U73122, blocked this
      translocation, but depletion of extracellular Ca2+ had no effect. The
      translocation was reversed by replacement with an iso-osmotic buffer. Our results
      demonstrate that the PH domain plays a critical role in the membrane targeting of
      PLC-delta1 and that the intracellular distribution of the enzyme is regulated by
      osmotic stress-driven phosphoinositide turnover.

PMID- 9918831
TI  - Glucocorticoid-mediated suppression of the promoter activity of the
      cyclooxygenase-2 gene is modulated by expression of its receptor in vascular
      endothelial cells.
AB  - Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is expressed
      selectively in response to various inflammatory stimuli such as
      lipopolysaccharide (LPS) and its expression is suppressed by the glucocorticoid
      dexamethasone (DEX) in numerous types of cells. However, LPS-enhanced production
      of prostacyclin in bovine arterial endothelial cells (BAEC) was not significantly
      decreased by treatment with DEX but was suppressed by selective COX-2 inhibitors.
      This is consistent with the finding that DEX was not effective at preventing the
      expression of LPS-induced COX-2 mRNA. Transient transfection analysis showed that
      DEX did not suppress the LPS-induced promoter activity of the 5'-flanking region
      of the human COX-2 gene (nucleotides -327 to +59). Since RNA blot analysis
      indicated low-level expression of glucocorticoid receptor (GR) mRNA in BAEC, a GR
      expression vector was transfected to evaluate the role of the GR in the COX-2
      promoter activity. It was found that DEX mediated the suppression of the LPS
      induced COX-2 promoter activity in a dose-dependent manner. These results suggest
      that the DEX-mediated suppression of LPS-induced promoter activity of the COX-2
      gene is modulated by expression of the GR, which will be possible to account for
      a unique expression pattern of the COX-2 gene in BAEC.

PMID- 9918832
TI  - Identification of inducible genes at the early stage of adipocyte differentiation
      of 3T3-L1 cells.
AB  - Adipocyte differentiation takes place via a complex series of steps. While
      PPARgamma2 and C/EBPalpha are known to be master regulators, the events at the
      earliest stage of adipocyte differentiation are not yet known. In this study, we
      cloned the genes which are induced at the beginning of differentiation of 3T3-L1
      preadipocyte cells. Of 58 clones obtained, only a few were already reported as
      the genes that are expressed differentially during adipocyte development. More
      than 30 clones are known but have been newly identified here as differentially
      expressed genes. Nineteen clones seemed to be unknown genes. The expression of
      RGS2, HSP105, Rho (TC10), VDR, and HIF-1alpha genes isolated here rapidly
      increased after the addition of inducers, and after 3-12 h the levels of
      expression decreased. The expression patterns of these mRNAs were different among
      growth-arrested and proliferating 3T3-L1 cells and NIH-3T3 cells, strongly
      indicating that some of the proteins identified here have crucial roles in the
      program of adipocyte differentiation.

PMID- 9918833
TI  - A dehydroalanyl residue can capture the 5'-deoxyadenosyl radical generated from S
      adenosylmethionine by pyruvate formate-lyase-activating enzyme.
AB  - The glycyl radical (Gly-734) contained in the active form of pyruvate formate
      lyase (PFL) of Escherichia coli is produced post-translationally by pyruvate
      formate-lyase-activating enzyme (PFL activase), employing adenosylmethionine
      (AdoMet) and dihydroflavodoxin as co-substrates. Previous 2H-labelings found
      incorporation of the pro-S hydrogen of Gly-734 into the 5'-deoxyadenosine co
      product, indicating that a deoxyadenosyl radical intermediate, generated by
      reductive cleavage of AdoMet, serves as the actual H atom abstracting species in
      this system. We have now examined an octapeptide (Suc-Arg-Val-Pro-DeltaAla-Tyr
      Ala-Val-Arg-NH2) that is analogous to the Gly-734 site of the PFL polypeptide but
      contains a dehydroalanyl residue (DeltaAla) in the glycyl position. Applied to
      the PFL activase reaction, this peptide becomes C-adenosylated at the olefinic
      beta carbon of DeltaAla. The modified peptide was isolated in micromol-quantities
      and characterized, after chymotryptic truncation, by MS and 2D NMR. PFL activase
      functions catalytically (kcat >/= 1 min-1) in the peptide modification reaction,
      which occurs with stoichiometric consumption of AdoMet. The mechanism appears to
      involve addition of the nucleophilic deoxyadenosyl radical to the electrophilic
      CC double bond of DeltaAla, followed by quenching of the peptide backbone
      centered adduct radical by the buffer medium. The trapping-property of the
      DeltaAla residue should be exploitable in investigating of how the Fe4S4 protein
      PFL activase generates the highly reactive deoxyadenosyl radical.

PMID- 9918834
TI  - Binding characteristics of dialkyl phthalates for the estrogen receptor.
AB  - Dialkyl phthalates have been suggested to function as xenoestrogen. To explore
      the structural essentials, a series of ring and alkyl-chain isomers of dialkyl
      phthalates C6H4(COOCnHm)2 were examined for their ability to displace [3H]17beta
      estradiol in the recombinant human estrogen receptor expressed on Sf9
      vaculovirus. Compounds with an alkyl chain of more than C3 (n = 3) exhibited a
      distinct full receptor binding in a dose-dependent manner. When the ring isomers
      of C3-diallyl (-CH2-CH=CH2) derivatives, namely diallyl phthalate, diallyl
      isophthalate, and diallyl terephthalate, were examined, the ortho isomer of
      diallyl phthalate was most potent to bind to the estrogen receptor. The
      interaction with the estrogen receptor was optimized with dibutyl phthalates of
      C4. The conformational studies by 1H-NMR measurements and ab initio molecular
      orbital calculations have suggested that the structure mimics the interface of
      steroid A and B/C rings of 17beta-estradiol. Dicyclohexyl phthalate bound to the
      estrogen receptor with a biphasic binding curve, suggesting the compound
      discriminates two different receptor conformations.

PMID- 9918835
TI  - Identification of the physiological promoter for spinocerebellar ataxia 2 gene
      reveals a CpG island for promoter activity situated into the exon 1 of this gene
      and provides data about the origin of the nonmethylated state of these types of
      islands.
AB  - In order to further use the spinocerebellar ataxia 2 (SCA2) promoter for
      transgenic mice models of "CAG repeat" neurodegeneration, different fragments of
      this 5' end were ligated into pGL3-Luc plasmid to obtain the better promoter
      activity of the physiological promoter for SCA2. Base-par composition of the SCA2
      5' region, and promoter prediction algorithms such as TSSW and TSSG, together
      with the high firefly luciferase expression after 48 hours of transient
      transfection in mammalian cells lines, showed a typical CpG island for promoter
      activity. The promoter activity was specifically localized into the exon 1 of the
      SCA2 gene. The higher expression of firefly luciferase in the embryonal F9 cells
      by the use of SCA2 promoter, rather than by the use of CMV promoter may be
      related with the origin of the nonmethylated CpG island during the early
      embryogenesis. Analysis of the 5' region from HD gene revealed to a CpG island,
      which could be containing the physiological promoter for this gene.

PMID- 9918837
TI  - Hamster diphtheria toxin receptor: a naturally occurring chimera of monkey and
      mouse HB-EGF precursors.
AB  - The sensitivity of mammalian cell lines to diphtheria toxin (DT) varies between
      species. Monkey (Mk) Vero cells are highly sensitive to DT, whereas rat and mouse
      (Ms) cells are resistant; hamster (Hm) cells display moderate DT sensitivity. The
      precursor of the Mk heparin-binding epidermal growth factor-like growth factor
      (proHB-EGF) functions as a DT receptor but the Ms proHB-EGF does not. In this
      study we have cloned, expressed, and characterized the Hm proHB-EGF/DT receptor.
      The expression of Hm proHB-EGF confers moderate DT sensitivity to normally DT
      resistant mouse cells. The amino acid sequence of Hm preproHB-EGF shows that,
      overall, it more closely resembles the Ms preproHB-EGF sequence, except in the DT
      binding region where it more closely resembles the Mk sequence. In the DT-binding
      region the Hm proHB-EGF sequence differs from the Mk proHB-EGF in only four amino
      acid residues (124, 126, 133, and 147); one of these residues, Ile133 in Mk proHB
      EGF, has been previously reported to be important for DT binding and sensitivity.
      Analysis of Mk proHB-EGF mutants with residues substituted for Ile133 suggests
      that Asn133 in Hm proHB-EGF may be responsible for the moderate DT sensitivity of
      Hm proHB-EGF-expressing cells.

PMID- 9918836
TI  - Validation of lucigenin as a chemiluminescent probe to monitor vascular
      superoxide as well as basal vascular nitric oxide production.
AB  - Lucigenin has been widely used as a chemiluminescent substrate to monitor
      vascular superoxide (O*-2) formation. The validity of lucigenin for detection of
      O*-2 has been questioned because O*-2 is generated by lucigenin itself. It has
      been shown that the concentration of lucigenin is a critical parameter affecting
      the validity of this assay. In the present studies we evaluated a reduced
      concentration of lucigenin (5 microM) as a tool to quantify O*-2 production in
      vascular tissue. Lucigenin-induced effects on endothelial function were assessed
      by isometric tension recording of isolated aortic rings suspended in organ baths.
      The effects of lucigenin on O*-2 production were studied using spin trapping and
      electron spin resonance spectroscopy. Lucigenin at 250 microM but not at 5 microM
      caused a significant attenuation of endothelium-dependent relaxations to
      acetylcholine, which was prevented by pretreatment with superoxide dismutase.
      Spin-trapping studies revealed that lucigenin at 250 microM increased vascular O*
      2 production several fold while 5 microM lucigenin did not stimulate O*-2
      production. Inhibition of NO synthase by NG-momomethyl-l-arginine as well as the
      removal of the endothelium almost doubled lucigenin-derived chemiluminescence
      (LDCL), indicating that basal production of endothelium-derived NO depresses the
      baseline chemiluminescence signal. Thus, lucigenin at a concentration of 5 microM
      seems to be a sensitive and valid probe for assessing O*-2 in vascular tissue. It
      can also be used as an indirect probe to estimate basal vascular NO release.

PMID- 9918838
TI  - How do skinned skeletal muscle fibers relax?
AB  - When free calcium is rapidly removed from skinned fibres using the photolabile
      Ca2+ chelator diazo-2, they relax without an appreciable change in sarcomere
      length (</=1.7%). This relaxation is faster than the turnover rate of cross
      bridges in steadily contracting muscle. Therefore a fall in the free calcium does
      not just prevent the recruitment of new cross-bridges but must also increase the
      rate of decay of cross-bridges which are already generating force. Increased
      levels of free phosphate (Pi) and free magnesium adenosine di-phosphate (MgADP)
      slow relaxation, indicating that during relaxation cross-bridges must undergo
      both a Pi and an ADP release step. In addition, we have observed that muscle
      relaxes in two phases. Phase 1, a linear phase, is greatly truncated in diazo-2
      relaxation compared to intact fibres, supporting the theory that this phase is
      governed by calcium removal from the thin filament regulatory system whilst Phase
      2 is a rapid exponential decline. Increased MgADP slows phase 1 consistent with a
      co-operative model of cross-bridge attachment where strongly-bound cross-bridges
      can maintain thin filament activation. The transition between phase 1 and 2 is
      not marked by any significant changes in sarcomere length (</=0.17%).

PMID- 9918839
TI  - Interaction of novel thiocolchicine analogs with the tubulin isoforms from bovine
      brain.
AB  - The antimitotic alkaloid colchicine binds to tubulin and inhibits microtubule
      assembly. Recently a new series of colchicine derivatives has been synthesized in
      which the seven-membered B-ring was shortened to a six-membered ring. In an
      effort to study the role of the B-ring substituents in this new series, we have
      studied the interaction of two compounds of this series, THC 5 and THC 18, with
      tubulin isoforms from bovine brain. We find that THC 18, which has a side chain
      with a pi-bonded SP2 conformation, binds differently to the tubulin isoforms,
      while THC 5 with a slightly different side chain does not. The results indicate
      that the conformation of the B-ring domain plays a major role in the differential
      interaction of a colchicine derivative with different tubulin isoforms. The
      results will be very important in designing potent antitumor derivatives of
      colchicine.

PMID- 9918840
TI  - The 26S proteasome assembly is regulated by a maturation-inducing hormone in
      starfish oocytes.
AB  - Changes in proteasome activities were observed during starfish oocyte maturation
      induced by a maturation-inducing hormone, 1-methyladenine. Succinyl-Leu-Leu-Val
      Tyr-MCA-hydrolyzing proteasome activity in immature oocytes showed a main peak of
      a 1500-kDa fraction and a shoulder centered at a 650-kDa fraction on Superose 6
      gel-filtration chromatography in the presence of ATP and glycerole. The 1500-kDa
      activity transiently decreased and then increased at about a half the time
      required for germinal vesicle breakdown (GVBD). In contrast, the 650-kDa activity
      showed only a slight change during the maturation process. The activity of the
      1500-kDa complex, unlike that of the 650-kDa complex, was immunoprecipitated with
      an antibody raised against regulatory subunits of mammalian 26S proteasomes,
      whereas both 1500- and 650-kDa activities were immunoprecipitated with anti-20S
      proteasome antibody. In addition, the 1500-kDa complex showed an ATP/ubiquitin
      dependent proteolytic activity. These results indicate that the 1500- and 650-kDa
      complexes correspond to the mammalian 26S and 20S proteasomes, respectively.
      Immunoblot analysis revealed that the change in the 26S proteasomal activity is
      due to the change in the amount of the 20S proteasome subcomplex. Taken together,
      the proteasome undergoes changes in molecular assembly and activities during
      hormone-induced oocyte maturation.

PMID- 9918841
TI  - Med8, a subunit of the mediator CTD complex of RNA polymerase II, directly binds
      to regulatory elements of SUC2 and HXK2 genes.
AB  - In a search to identify new factors required for expression of SUC2 gene in
      Saccharomyces cerevisiae, we have partially purified a 27 kDa protein (p27) that
      bound both the DRSs of the HXK2 gene and the UASs of SUC2 gene. The amino
      terminal sequence of p27 identified the MED8 gene (open reading frame YBR193C),
      located in chromosome II of S. cerevisiae, as the gene coding for the protein.
      Disruption of this gene has demonstrated that is an essential gene for yeast
      growth. To determine whether the p27 protein represents the Med8 product, we
      expressed MED8 gene in E. coli and demonstrated that the heterologous synthesized
      protein specifically binds to both UASSUC2 and DRS2HXK2. This observation
      suggests that Med8 may be important for the coupling of the glucose repression
      pathway of SUC2 gene to the HXK2 gene expression. Med8 has been described as a
      mediator protein interacting with the CTD of the RNA polymerase II. Thus, the
      role of Med8 could be to act as coupling factor by linking activating and
      repressing transcription complexes to the RNA polymerase II holoenzyme
      transcriptional machinery.

PMID- 9918842
TI  - Heterogeneous nuclear ribonucleoprotein I (hnRNP-I/PTB) selectively binds the
      conserved 3' terminus of hepatitis C viral RNA.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus whose genome is replicated
      by a direct RNA-to-RNA mechanism. Initiation of negative-strand RNA synthesis is
      believed to proceed from the 3' end of the genomic RNA. The high conservation of
      the 3' terminus suggests that this region directs the assembly of proteins
      required for the initiation of RNA replication. We sought to determine whether
      host proteins bind specifically to this RNA structure. We observed specific
      binding of cellular proteins to labeled 3'-terminal RNA by mobility shift
      analysis. UV crosslinking revealed that the predominant 3'-terminal RNA-binding
      protein migrates as a single, 60-kDa species that can be precipitated by
      monoclonal antibodies directed against heterogeneous nuclear ribonucleoprotein I,
      also called polypyrimidine tract-binding protein (hnRNP-I/PTB), a protein
      previously shown to bind to the 5' internal ribosome entry site (IRES) of the HCV
      genome. Purified hnRNP-I/PTB also bound selectively to the 3' end of the HCV
      genome. hnRNP-I/PTB binding requires the upstream two stem-loop structures (SL2
      and SL3) but not the most 3'-terminal stem-loop (SL1). Minor alteration of either
      the stem or loop sequences in SL2 or SL3 severely compromised hnRNP-I/PTB
      binding, suggesting extremely tight RNA structural requirements for interaction
      with this protein. hnRNP-I/PTB does not bind to either end of the antigenomic RNA
      strand and binds to the 5' IRES element of the genome at least 10-fold less
      avidly than to the 3' terminus. The strong, selective, and preferential binding
      of hnRNP-I/PTB to the 3' end of the HCV genome suggests that it may be recruited
      to participate in viral replication, helping to direct initiation of negative
      strand RNA synthesis, stabilize the viral genome, and/or regulate encapsidation
      of genomic RNA.

PMID- 9918843
TI  - A mutant of deleted variant of hepatocyte growth factor (dHGF) with alanine
      substitution in the N-terminal basic region has higher activity in vivo.
AB  - In a previous study, we generated a mutant of dHGF (deleted variant of hepatocyte
      growth factor), termed #2, with higher specific activity than dHGF in assays of
      mitogenic activity on rat hepatocytes and America opossum kidney epithelial cells
      (OK). In the present study, we examine in vivo hepatotropic and renotropic
      activities of #2 and its distribution to target tissues, liver and kidney.
      Administration of #2 to normal rats significantly increased serum levels of total
      protein, albumin, free-cholesterol, and HDL-cholesterol and liver weight in a
      dose-dependent manner. Analysis of these parameters suggests that #2 is more
      potent than dHGF as a hepatotropic factor in vivo. In addition, #2 reduced
      mortality of mercuric chloride-administered mice and the effect was stronger than
      that of dHGF. When injected to mice, a larger amount of #2 than dHGF was rapidly
      distributed to the liver. Sixty minutes after injection, the concentrations of #2
      in plasma, liver, and kidney were higher than those of dHGF. These distribution
      properties and the higher mitogenic activity in vitro may explain why #2 exerts
      more potent in vivo biological activity than dHGF.

PMID- 9918844
TI  - Activation of Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6
      cells by flavonoids: genistein, daidzein, and apigenin.
AB  - The present study investigates regulation of Cl- channels and Na+/K+/2Cl-
      cotransporter in a renal epithelial cell line, A6, by flavones: genistein [an
      inhibitor of protein tyrosine kinases (PTK)], daidzein (an inactive compound of
      genistein), and apigenin [an inhibitor of mitogen-activated protein (MAP)
      kinase]. Genistein and daidzein activated Cl- channels. Genistein and apigenin
      had a stimulatory effect on the bumetanide-sensitive Na+/K+/2Cl- cotransporter.
      Other PTK inhibitors, tyrphostin A23, lavendustin A, and herbimycin A, which do
      not contain a structure flavone, had no stimulatory action on Cl- channels or the
      Na+/K+/2Cl- cotransporter. These observations conclude that (i) genistein
      activates a Cl- channel and the Na+/K+/2Cl- cotransporter; and (ii) the
      stimulatory action is not mediated through its inhibitory action on protein
      tyrosine kinase, but rather the structure of flavone itself plays a crucial role
      in stimulatory regulation of Cl- channels and Na+/K+/2Cl- cotransporter.

PMID- 9918845
TI  - Phosphorylation and dephosphorylation of the B subunit of DNA polymerase alpha
      primase complex in the early embryogenesis of Drosophila.
AB  - In the early embryos of Drosophila, the B subunit of the DNA polymerase alpha
      primase complex was found to migrate more slowly during the first 13 mitotic
      cycles than that from cycle 14 using SDS-polyacrylamide gel electrophoresis.
      Lambda phosphatase treatment showed that the reduced migration was caused by
      phosphorylation of the B subunit. Detailed analysis using the partially purified
      B subunit indicated that most of the B subunit until cycle 13 was a
      phosphorylated form while the B subunit of cycle 14 was a dephosphorylated form.

PMID- 9918846
TI  - Fish androgen receptor: cDNA cloning, steroid activation of transcription in
      transfected mammalian cells, and tissue mRNA levels.
AB  - We have previously identified 11-ketotestosterone (11KT, a portent androgen in
      teleosts) as the spermatogenesis-inducing hormone of the Japanese eel. In this
      study, a cDNA encoding the eel androgen receptor (AR) was isolated from the
      Japanese eel testis. This cDNA contains a complete open reading frame encoding
      848 amino residues. The amino acid sequence of the eel AR shows high homology
      with other ARs. In transient transfection assays of mammalian cells, the eel AR
      showed androgen-dependent activation of transcription from the androgen
      responsive MMTV promoter. Of the endogenous androgens found in the Japanese eel,
      11KT was the most effective activator of transcription. These results indicate
      that the cloned cDNA encodes a functional eel AR, and its major native ligand is
      11KT. This is the first isolation of an AR molecule from fish, and is the first
      evidence that 11KT acts via a nuclear receptor.

PMID- 9918847
TI  - Microphthalmia-associated transcription factor interacts with PU.1 and c-Fos:
      determination of their subcellular localization.
AB  - Marked osteopetrosis is observed only in mi/mi mutant mice although normal
      osteoclastgenesis is observed in other mutant mice including null mutants at the
      mi locus. Mutant microphthalmia-associated transcription factor (mi-MITF) has
      defective nuclear localization potential. We found normal MITF (+-MITF)-c-Fos and
      mi-MITF-c-Fos complexes in the cytoplasm by immunoblotting, and showed that PU.1
      bound with both +-MITF and mi-MITF using an electrophoretic mobility shift assay.
      Furthermore, the nuclear localization of PU.1 and c-Fos was inhibited by over
      expressed mi-MITF in WEHI-3 cells. These results indicate that mi-MITF expressing
      in osteoclasts specifically binds to c-Fos and PU.1 which are essential
      transcription factors of osteoclastgenesis and that mi-MITF blocks the nuclear
      localization of these other transcription factors, which may result in
      osteopetrosis in mi/mi mutant mice.

PMID- 9918848
TI  - Cleavage of RXRalpha by a lysosomal enzyme, cathepsin L-type protease.
AB  - In this study, we characterized a protease responsible for the cleavage of
      RXRalpha in two human derived cell lines, HepG2 and JEG-3 cells. Electrophoretic
      mobility shift assay (EMSA) combined with antibody supershift analysis suggested
      that contamination of cytoplasmic components during nuclear extract preparation
      could result in complete cleavage of RXRalpha at its N-terminus in JEG-3 cells,
      while such proteolytic activity was much less evident in HepG2. When the nuclei
      were purified in the presence of leupeptin, only full-length RXRalpha was found
      in the extracts prepared from both JEG-3 and HepG2 cells, suggesting a member of
      cysteine protease family is responsible for the cleavage. The presence of the
      protease in the cytoplasm, but not in the nucleus, was confirmed by incubating
      full-length 35S-labeled RXRalpha with each fraction. The cytoplasmic fraction
      from JEG-3 and HepG2 cells cleaved RXRalpha into smaller sizes with molecular
      mass of 45, 43, and 31 kD. Immunoprecipitation with antibodies recognizing
      distinct epitopes indicated that the cleaved RXRalpha with the size of 45 and 43
      kD were truncated at N-terminus in which most of the A/B domain was absent. Using
      a series of protease inhibitors, the enzyme cleaving RXRalpha was characterized
      as cathepsin L-type protease. The enzyme activity in JEG-3 cells was much higher
      than that in HepG2 cells. This is the first demonstration that RXRalpha is
      cleaved by a lysosomal enzyme, cathepsin L-type protease.

PMID- 9918849
TI  - Evidence against the current hypothesis of "gene dosage effects" of trisomy 21:
      ets-2, encoded on chromosome 21" is not overexpressed in hearts of patients with
      Down Syndrome.
AB  - BACKGROUND: The major current concept for the pathogenesis of the Down Syndrome
      (DS) phenotype including congenital heart disease (CHD) is the so-called "gene
      dosage effect." According to this hypothesis, genes encoded by chromosome 21 at
      the "critical region" (which is thought to be crucial for the development of the
      DS phenotype) are overexpressed in the trisomic state, thus leading to an
      imbalance of genes as, e.g., the protooncogene ets-2, superoxide dismutase, etc.
      METHODS: We studied heart biopsies obtained at surgery from 6 patients with DS
      and 7 patients with congenital heart disease. ets-2-mRNA steady state levels were
      determined by a competitive reverse transcription-polymerase chain reaction (RT
      PCR) technique which allowed the determination of this gene at the attomol level.
      RESULTS: ets-2 mRNA in total ventricular tissue of DS patients showed
      concentrations of 0.60 +/- 0.42 fg/10 ng total RNA (mean, +/- SD). When
      normalized versus the housekeeping gene beta-actin to rule out general
      transcriptional changes in that disorder, the ratio of 0.56 +/- 0.28 (mean, +/-
      SD) was calculated. ets-2 mRNA in total ventricular tissue of patients with non
      DS CHD showed concentrations of 0.45 +/- 0.22 fg/10 ng total RNA (mean, +/-SD)
      and ratios of 0.48 +/- 0.35 (mean, +/-SD). No differences could be found at the
      p<0.05 level. CONCLUSION: No absolute quantification of a gene incriminated in
      the "gene dosage effect-hypothesis" was performed so far and the only approach to
      (semi-) quantitative determination of the ets-2 gene using northern blotting was
      published on one individual DS sample only. This is the first report to clearly
      show that no overexpression of ets-2 can be found in heart of patients with DS,
      thus providing evidence against the current gene dosage effect-hypothesis.

PMID- 9918850
TI  - Cholecystokinin-induced redistribution of paxillin in rat pancreatic acinar
      cells.
AB  - Cholecystokinin (CCK) dose-dependently stimulates enzyme secretion or loss of
      cell integrity in the exocrine pancreas. Signaling mechanims include tyrosine
      phosphorylation of p125(FAK) and paxillin. Here, we examine their potential
      function. Maximum phosphorylation of both proteins was observed after stimulation
      of freshly isolated rat pancreatic acini with 10 nM CCK, a concentration known to
      initiate breakdown of the terminal actin web and cell damage. Under these
      conditions, CCK initiated transient redistribution of paxillin from the apical
      cytosol to the apical and lateral plasma membrane within 2 min, where it
      colocalized with the terminal actin web. Relocation of paxillin was confirmed in
      subcellular fractions by western blotting and coincided with maximum
      phosphorylation of membrane-bound p125(FAK) and paxillin. Subsequently, paxillin
      was redistributed to the basolateral cytosol and was degraded. p125(FAK) remained
      membrane-bound. We conclude that phosphorylation and redistribution of paxillin
      and phosphorylation of p125(FAK) may participate in the CCK-induced disassembly
      of acinar cell actin.

PMID- 9918851
TI  - Solution structure of a beta-neurotoxin from the New World scorpion Centruroides
      sculpturatus Ewing.
AB  - We report the detailed solution structure of the 7.2 kDa protein CsE-I, a beta
      neurotoxin from the New World scorpion Centruroides sculpturatus Ewing. This
      toxin binds to sodium channels, but unlike the alpha-neurotoxins, shifts the
      voltage of activation toward more negative potentials causing the membrane to
      fire spontaneously. Sequence-specific proton NMR assignments were made using 600
      MHz 2D-NMR data. Distance geometry and dynamical simulated annealing refinements
      were performed using experimental distance and torsion angle constraints from
      NOESY and pH-COSY data. A family of 40 structures without constraint violations
      was generated, and an energy-minimized average structure was computed. The
      backbone conformation of the CsE-I toxin shows similar secondary structural
      features as the prototypical alpha-neurotoxin, CsE-v3, and is characterized by a
      short 2(1/2)-turn alpha-helix and a 3-strand antiparallel beta-sheet, both held
      together by disulfide bridges. The RMSD for the backbone atoms between CsE-I and
      CsE-v3 is 1.48 A. Despite this similarity in the overall backbone folding, the
      these two proteins show some important differences in the primary structure
      (sequence) and electrostatic potential surfaces. Our studies provide a basis for
      unravelling the role of these differences in relation to the known differences in
      the receptor sites on the voltage sensitive sodium channel for the alpha- and
      beta-neurotoxins.

PMID- 9918852
TI  - Genomic structure, 5' flanking sequences, and precise localization in 1P31.1 of
      the human prostaglandin F receptor gene.
AB  - This paper describes the genomic structure of the human Prostaglandin F receptor
      gene (FP) with its exon-intron borders and 5' flanking sequences. Furthermore,
      the location of the gene has been localized to a very small region on 1p31.1
      using FISH and radiation hybrids analysis. The PGF receptor (FP) is highly
      expressed in mouse tissues especially in the corpora lutea in ovaries and in the
      kidney. Recently, it has been shown that homozygous knockout-mice lacking the
      gene for this receptor are unable to deliver normal fetuses at term. It might be
      speculated that the lack of the FP gene has the same effect in human as in mouse.
      Mutation analysis in families with difficulties in parturition would therefore be
      of high interest. The results presented here provides data necessary for further
      investigations of the FP gene.

PMID- 9918853
TI  - Identification and characterization of nuclear pore subcomplexes in mitotic
      extract of human somatic cells.
AB  - In higher eukaryotic cells, it is generally thought that nuclear pore complex
      disassembles at the beginning of mitosis and reassembles at the end. Using a
      monoclonal antibody that recognizes nuclear pore antigens, we found that, at
      mitosis of mammalian somatic Hela cells, the nuclear pore complex disassembles
      into at least three subcomplexes, termed subcomplexes A, B and C (molecular mass;
      2 MDa<, approximately 660 kDa, and approximately 440 kDa, respectively). The
      direct partial amino acid sequencing of the components of these subcomplexes
      indicates that the A subcomplex contains CAN/Nup214/p250 and p62 and the B
      subcomplex also contains p62, indicating that p62 is contained in two different
      subcomplexes. Subcomplex C was shown to consist of Nup98 and human RAE1, a human
      homolog of yeast Rae1p/Gle2p. Since Nup98 and Rae1p/Gle2p have been reported to
      be involved in mRNA export, this suggests that some of the mitotic subcomplex may
      be formed by functionally related proteins.

PMID- 9918854
TI  - Regulation of ground squirrel Na+K+-ATPase activity by reversible phosphorylation
      during hibernation.
AB  - Maintenance of skeletal muscle energy status during hibernation in ground
      squirrels, Spermophilus lateralis, was accompanied by a decrease in Na+K+-ATPase
      pump activity. Energy charge was maintained (0.89) during hibernation at the
      expense of total adenylates (decreased by 41%). Muscle Na+K+-ATPase activity was
      9.1 U/mg protein in euthermic controls but decreased by 60% during hibernation.
      Enzyme activity was similarly suppressed in vitro when extracts of control muscle
      were incubated with ATP plus second messengers of protein kinases A, G or C
      whereas stimulation of protein phosphatases in muscle extracts from hibernators
      increased Na+K+-ATPase activity. Additional studies confirmed that suppression
      and reactivation of the enzyme in euthermic muscle extracts can be achieved with
      protein kinase A and alkaline phosphatase treatments, respectively, and indicated
      that phosphorylation changes the ATP dependency of the enzyme. Thus, hibernation
      induced suppression of Na+K+-ATPase activity in muscle and other organs of ground
      squirrels, which is a key part of the overall suppression of metabolic rate that
      constitutes torpor, appears to be regulated via reversible protein
      phosphorylation.

PMID- 9918855
TI  - Pyruvate kinase as a microtubule destabilizing factor in vitro.
AB  - Endogenous control of microtubule dynamism is essential in many cell types.
      Numerous microtubule-adhering proteins stabilize the polymer status, while very
      few protein factors are described with opposite effects. The brain- and muscle
      specific M1 isoform of the enzyme pyruvate kinase is investigated here in this
      respect. Three pieces of evidence indicate antimicrotubular effects of this
      protein. (1) Pyruvate kinase inhibits taxol-induced tubulin polymerization into
      microtubules as revealed by turbidimetry. (2) Pelleting experiments show that
      pyruvate kinase partially disassembles taxol-stabilized microtubules into less
      sedimentable oligomers leading to the appearance of tubulin in the supernatant
      fractions. (3) Electron microscopy reveals the kinase-induced formation of great
      amounts of thread-like tubulin oligomers which tend to accumulate in a light/less
      sedimentable fraction. Immunoelectron micrographs using labeled antibody against
      pyruvate kinase provide evidence for the binding of pyruvate kinase to the thread
      like oligomeric forms. The present data allow the assumption that pyruvate kinase
      may display multiple regulatory functions as a glycolytic control enzyme and as a
      modulator of microtubule dynamism.

PMID- 9918856
TI  - Synchronization of glucose-induced Ca2+ transients in pancreatic beta-cells by a
      diffusible factor.
AB  - Glucose is known to induce transients of cytoplasmic Ca2+ by mobilizing
      intracellular stores when pancreatic beta-cells are exposed to glucagon. Dual
      wavelength microfluorometry with fura-2 was used to study such transients in
      individual beta-cells isolated from ob/ob-mice. The Ca2+ transients were often
      synchronized in beta-cells situated up to 80 microm apart. The messenger might be
      nitric oxide, as indicated from a decreased number of synchronized transients in
      the presence of 500 micromol/l oxyhemoglobin or 10 mmol/l Nomega-nitro-L-arginine
      methyl ester. The discovery that Ca2+ transients are synchronized in the absence
      of cell contact indicates the involvement of a diffusible factor in coordinating
      the activity of the insulin-releasing beta-cells.

PMID- 9918857
TI  - p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates
      with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand
      stimulated hematopoietic cells.
AB  - Flt3/Flk2 belongs to class III receptor tyrosine kinases. Like other members of
      type III receptor tyrosine kinases, murine Flt3 induces tyrosine phosphorylation
      of p85 and subsequently activation of PI3 kinase upon FL binding. While p85 binds
      murine Flt3 at Y958 in the carboxyl terminus of the receptor, human Flt3 does not
      have a potential p85-binding site in the carboxyl terminus. In this study, we
      examined whether p85 binds to human Flt3 in Baf3/Flt3 and THP-1 cells. In
      contrast to murine Flt3, p85 is not tyrosine phosphorylated after FL stimulation,
      nor does it bind Flt3 in both cell lines. Instead p85 associates inducibly with
      tyrosine phosphorylated SHP-2 and constitutively with SHIP and two tyrosine
      phosphorylated proteins with molecular weights about 100-kDa (p100) and 120-kDa
      (p120) in Baf3/Flt3 cells. The p100 associates with both p85 and SHP-2. In THP-1
      cells, p85 associates inducibly with tyrosine phosphorylated SHIP, p100 and p120.
      These results indicate that p85 does not bind human Flt3, but forms a complex
      with SHP-2, SHIP, p100 and p120 in hematopoietic cells.

PMID- 9918858
TI  - Arachidonic acid as a messenger for the expression of long-term potentiation.
AB  - Arachidonic acid is suggested to play a role in the expression of long-term
      potentiation (LTP), a synaptic analog of memory and learning. However, it is
      unknown whether this free fatty acid is actually released during LTP or not. To
      address this question, we assayed arachidonic acid with an HPLC system using 9
      anthryldiazomethane (ADAM) as a fluorescent probe. High frequency stimulation
      (tetanic stimulation) to a hippocampal slice from the guinea pig brain caused a
      huge increase in the release of glutamate from presynaptic terminals and in turn,
      a gradual increase in the release of arachidonic acid. A similar increase in the
      release of arachidonic acid was induced by application of glutamate and the
      increase was inhibited by either the selective AMPA/kainate receptor antagonist,
      DNQX, or to a lesser extent by the selective NMDA receptor antagonist, APV. These
      findings suggest that arachidonic acid is produced by activation of ionotropic
      glutamate receptors involving expression of LTP. Arachidonic acid exerted a long
      lasting facilitatory action on synaptic transmission in the CA1 region of rat
      hippocampal slices and the facilitation occluded the tetanic LTP. Arachidonic
      acid, thus, appears to be a significant factor for the expression of LTP.

PMID- 9918860
TI  - Sp1 phosphorylation by Erk 2 stimulates DNA binding.
AB  - EGF stimulates gene expression through a variety of signal transduction pathways
      that include the ras-Erk pathway. We have shown previously that EGF receptor
      activation stimulates gastrin gene expression through a GC-rich element called
      gERE. This element binds Sp1 family members and raises the possibility that the
      ras-Erk signal transduction cascade may target this novel EGF responsive element.
      Moreover, it is known that Erk 2 is capable of phosphorylating other mitogen
      inducible transcription factors, e.g., Elk, Sap suggesting that Erk may also
      inducibly phosphorylate Sp1. To test this hypothesis directly using
      cotransfection experiments, we show that ras and Erk 2 activation indeed target
      the gERE element. The Mek 1 kinase inhibitor, PD98059, blocks 50% of EGF
      inducible gastrin promoter activity. Pretreatment of the extracts with
      recombinant Erk2 stimulated Sp1 binding; whereas dephosphorylation reduced but
      did not eliminate Sp1 binding. Together, these studies demonstrate the novel
      finding that inducible binding of Sp1 is regulated by its state of
      phosphorylation. Further, gastrin promoter activation is mediated in part by the
      ras-Erk signaling cascade that targets Sp1.

PMID- 9918859
TI  - Pro12Ala missense mutation of the peroxisome proliferator activated receptor
      gamma and diabetes mellitus.
AB  - Peroxisome proliferator activated receptor-gamma (PPARgamma) is a nuclear
      receptor that regulates adipocyte differentiation and possibly lipid metabolism
      and insulin sensitivity. Therefore, PPARgamma is a promising candidate gene for
      several disorders including diabetes, obesity, and dyslipoproteinemia. Screening
      for mutations in the entire coding region of the PPARgamma gene yielded a
      missense C --> G mutation at codon 12, resulting in the substitution of proline
      with alanine (Pro12Ala). The objective of our study was to examine the
      relationship between this genetic variant and diabetes and associated diseases in
      a large group of patients with type 1 (n = 522) and type 2 (n = 503) diabetes.
      Allelic frequencies of the PPARgamma2 12Ala allele were similar between patients
      with either type of diabetes and comparable to that in healthy controls (n =
      310). There was also no significant relationship between dyslipoproteinemia or
      obesity and the PPARgamma2 Pro12Ala genotype. Thus, our data, in this large and
      ethnically homogenous group of patients, do not support the hypothesis that this
      genetic variant is strongly associated with diabetes, obesity, or dyslipidemia in
      patients with type 1 or type 2 diabetes mellitus. This genetic marker is
      therefore unlikely to serve as a clinically useful predictor of these disorders
      in Caucasian patients with diabetes mellitus.

PMID- 9918861
TI  - Pulsatile stretch stimulates vascular endothelial growth factor (VEGF) secretion
      by cultured rat cardiac myocytes.
AB  - Evidence has accumulated that vascular endothelial growth factor (VEGF) is
      expressed in the heart, and its expression is markedly increased in response to
      hypoxia. Recently, it was shown that pulsatile myocardial stretch in vivo
      markedly enhanced VEGF mRNA level in the heart. To investigate whether pulsatile
      mechanical stretch really stimulates VEGF expression by cardiac myocytes, using
      an in vitro preparation, we examined the secretion of VEGF into the culture media
      from cardiac myocytes subjected to pulsatile stretch. We found that pulsatile
      mechanical stretch induced rapid secretion of VEGF by cultured rat cardiac
      myocytes and mRNA expression of VEGF and VEGF receptors in the cardiac myocytes.
      We also found that the stretch-induced secretion of VEGF was at least in part
      mediated by TGF-beta. These data provide the direct evidence that mechanical
      overload itself can induce VEGF secretion by cardiac myocytes, which may play a
      role in ameliorating the relative myocardial hypoxia.

PMID- 9918862
TI  - Optical mapping of DNA polymerase I action and products.
AB  - Single molecule approaches to the characterization of biochemical systems offer
      an intrinsically simple and direct approach to address difficult, previously
      unyielding problems. Optically based approaches have recently been used to
      construct high resolution, ordered restriction maps from a variety of clone
      types. Advancements in surface technologies have enabled the reliable elongation
      and fixation of large DNA molecules onto specially derivatized substrates with
      retention of biochemical accessibility. In this study, the addition of
      fluorescently labeled nucleotides to surface-mounted DNA molecules by the action
      of DNA polymerase I is investigated using fluorescence microscopy to image
      individual template molecules. Molecules undergoing nick translation and
      containing only a few fluorochromes are readily imaged. These novel results
      suggest that surface-bound molecules may serve as a substrate for a broad range
      of enzymatic actions, and may offer new routes to analysis when coupled to
      advanced imaging techniques.

PMID- 9918863
TI  - Cloning and characterization of DYRK1B, a novel member of the DYRK family of
      protein kinases.
AB  - The DYRK1A gene on human chromosome 21 encodes a protein kinase presumed to be
      involved in the pathogenesis of mental retardation in Down's syndrome. Here we
      describe a highly similar homolog, DYRK1B, which is, in contrast to DYRK1A,
      predominately expressed in muscle and testis. The human DYRK1B gene was mapped to
      chromosome 19 (19q12-13.11) by radiation hybrid analysis. The amino acid
      sequences of DYRK1A and DYRK1B are 84% identical in the N-terminus and the
      catalytic domain but show no extended sequence similarity in the C-terminal
      region. DYRK1B contains all motifs characteristic for the DYRK family of protein
      kinases. In addition, the sequence comprises a bipartite nuclear localization
      motif. A green fluorescent protein (GFP) fusion protein of DYRK1B was found
      mainly in the nucleus of transfected COS-7 cells. These data suggest that DYRK1B
      is a muscle- and testis-specific isoform of DYRK1A and is involved in the
      regulation of nuclear functions.

PMID- 9918864
TI  - Oncogenic ras fails to restore an in vivo tumorigenic phenotype in embryonic stem
      cells lacking vascular endothelial growth factor (VEGF).
AB  - Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis.
      Previous studies have shown that the ability of murine embryonic stem (ES) cells
      to form teratocarcinomas in nude mice is substantially reduced following targeted
      inactivation of the VEGF gene. We sought to determine whether VEGF-/- ES cells'
      tumorigenic phenotype can be rescued by transfection with a mutant H-ras. VEGF-/-
      ES cells were transfected with expression vector which directs the constitutive
      synthesis of oncogenic Val-12 ras. Expression of ras protein was documented by
      Western blot analysis. We injected several clones with different levels of Val-12
      ras expression in nude mice. In agreement with our earlier report, VEGF-/- ES
      cells formed much smaller tumors than control ES cells. However, none of the ras
      expressing clones tested formed tumors larger than those derived from parental
      VEGF-/- cells. Thus, pluripotent cells such as ES cells are unable to compensate
      for the loss of VEGF even in the presence of a potent oncogenic stimulus such as
      mutant ras. These findings strengthen the hypothesis that VEGF-mediated
      angiogenesis is crucial for effective in vivo tumor growth.

PMID- 9918865
TI  - Role of Trp-187 in the annexin V-membrane interaction: a molecular mechanics
      analysis.
AB  - The minimized energy mapping of annexin V Trp-187 chi1 x chi2 isomerization
      supports the existence of two preferential rotameric orientations of the Trp side
      chain upon annexin V binding to membranes, in agreement with the time-resolved
      fluorescence results. They correspond to the perpendicular trans (-173 degrees,
      73 degrees) and g- (-71 degrees, 83 degrees) rotamers and represent 59 and 28% of
      the population, respectively. The analysis of their local environment makes it
      possible to assign the trans rotamer to the long component and the g- rotamer to
      the short component of the biexponential fluorescence decay. The orientation of
      these rotamers relative to the protein core suggests a dual role for Trp-187,
      which might be involved both in the interaction with the phospholipid bilayer and
      in the formation of the annexin V 2-D array at the surface of the membrane.

PMID- 9918866
TI  - Expression, subcellular localization, and cloning of the 130-kDa regulatory
      subunit of myosin phosphatase in porcine aortic endothelial cells.
AB  - In endothelial cells in situ and in primary culture, immunoblot analysis revealed
      an expression of the 130-kDa subunit of myosin phosphatase, similar to the myosin
      phosphatase targeting subunit (MYPT) of smooth muscle. Screening of an
      endothelial cell cDNA library yielded a clone encoding an NH2-terminal fragment
      of 89.6 kDa, closely related to smooth muscle MYPT1. Two isoforms differing by a
      central insert of 56 residues were detected. In growing cells, MYPT1 was
      localized on stress fiber, but at confluence the localization pattern changed and
      MYPT1 was distributed close to the cell membrane and at cell-cell contacts. The
      membrane localization of MYPT1 suggested a target other than myosin and raised
      the possibility that MYPT1 may be involved in dephosphorylation of alternative
      substrate(s). These distinct mechanisms would also be dependent on the growth
      state of the endothelial cells, i.e., regulation of actin-myosin interactions in
      growing cells and an unknown function in cells at confluence.

PMID- 9918867
TI  - Identification of thyroid hormone transporters.
AB  - Thyroid hormone action and metabolism are intracellular events that require
      transport of the hormone across the plasma membrane. We tested the possible
      involvement of the Na+/taurocholate cotransporting polypeptide (Ntcp) and organic
      anion transporting polypeptide (oatp1) in the hepatic uptake of the prohormone
      T4, the active hormone T3, and the metabolites rT3 and 3,3'-T2. Xenopus laevis
      oocytes were injected with 2.3 ng Ntcp or oatp1 cRNA and, after 2-3 days,
      incubated for 1 h at 25 degrees C with usually 0.1 microM 125I-labeled ligand.
      Uninjected oocytes showed marked uptake of iodothyronines and this was further
      increased by Ntcp and oatp1 cRNA, i.e., 1.9- and 2.8-fold for T4, 1.7- and 1.7
      fold for T3, 1.8- and 6.0-fold for rT3, and 1.3- and 1.4-fold for 3,3'-T2,
      respectively. Mostly due to much lower uptake by uninjected oocytes, Ntcp and
      oatp1 cRNA induced larger, 12- to 76-fold increases in uptake of iodothyronine
      sulfates. The Ntcp cRNA-induced iodothyronine uptake was completely inhibited in
      Na+-deplete medium, whereas the oatp1 cRNA-induced uptake was not affected. These
      results suggest that hepatic uptake of thyroid hormones and their metabolites is
      mediated at least in part by Ntcp and oatp1.

PMID- 9918868
TI  - Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle
      cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of
      triacylglycerol (TG) were dose dependently incorporated into phospholipid
      fraction of vascular smooth muscle cells (VSMC) and suppressed the proliferation
      of VSMC. Flow cytometric analysis demonstrated both EPA and DHA inhibited G1/S
      progression. EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2
      kinase activity without altering the amount of cyclin E and p27(kip1) proteins
      and cyclin dependent kinase activating kinase activity by growth stimulation.
      This mechanisms remained to be clarified but this is the first report of a novel
      mechanisms of inhibition of DNA synthesis by EPA and DHA.

PMID- 9918869
TI  - Long-extension PCR to detect deleted mitochondrial DNA molecules is compromized
      by technical artefacts.
AB  - Long-extension PCR (LX-PCR), followed by Southern hybridization to probes for two
      different regions of the mitochondrial genome, was used to evaluate the presence
      of deleted mtDNA molecules in heart muscle samples from alcoholic cardiomyopathy
      patients compared with age-matched controls. Two different primer pairs capable
      of amplifying the entire genome, as well as a variety of other primer pairs
      predicted to amplify the genome in large, overlapping fragments, were tested.
      Products indicating the presence of a variety of subgenomic, deleted molecules
      were detected in variable amounts from patient and control myocardial samples
      alike. Most of these hybridized with a probe for the 16S/ND1 region, but not with
      a probe for the ND4/ND5 region that is commonly deleted. Dilution of a given
      template DNA in which deleted products were prominent resulted in the
      disappearance of the subgenomic bands in favour of the full-length, undeleted
      product. Therefore, the appearance and amount of such products is subject to
      template concentration or quality. The results indicate that the application of
      LX-PCR to the detection and quantitation of deleted mtDNAs is inherently
      unreliable, and findings using this technique should be treated with caution
      unless supported by an independent method.

PMID- 9918872
TI  - Barley yellow dwarf virus RNA requires a cap-independent translation sequence
      because it lacks a 5' cap.
AB  - A 3' translation enhancer (3'TE) sequence that facilitates cap-independent
      translation is located near the 3' end of barley yellow dwarf luteovirus RNA.
      Here, we show that the 3'TE is required for translation of the viral genome and
      thus for viral replication. Antisense inhibition showed that the 3'TE has
      significant secondary structure and is required for translation of virion RNA
      from infected plants and uncapped genomic transcripts but not for translation of
      capped transcripts. Direct end-labeling of RNAs verified the absence of a 5'
      modification on virion RNA. Thus barley yellow dwarf virus differs from related
      viruses by having neither a genome-linked protein nor a 5' cap.

PMID- 9918871
TI  - Structural conservation of Notch receptors and ligands.
AB  - The Notch signalling pathway is an evolutionarily conserved cell-to-cell
      communication system utilized multiple times and in many tissues during
      development. The outcome of an interaction between Notch and its ligands is
      highly influenced by factors both extrinsic and intrinsic to Notch expressing
      cells, suggesting that Notch functions either directly or in parallel with other
      signalling systems to regulate cellular differentiation events. Protein domains
      common to all ligands and receptors of this system suggest conserved functional
      properties that likely relate to regulatory mechanisms for Notch signalling.
      Within this review, the known functional properties of these domains are analyzed
      with respect to their contributions to ligand/receptor interactions and Notch
      signalling.

PMID- 9918873
TI  - In vivo disturbance of hematopoiesis in mice persistently infected with murine
      cytomegalovirus: impairment of stromal cell function.
AB  - Although the pathogenic effects of a primary cytomegalovirus (CMV) infection on
      hematopoiesis has been largely investigated so far, the effects of a persistent
      or latent infection have yet to be elucidated. The effects of persistent CMV
      infection on hematopoiesis thus were examined using BALB/c mice at 4 weeks
      postinfection with 0. 2 LD50 of murine CMV (MCMV) infection as a persistent
      infection model. The parameters of constitutive hematopoiesis of MCMV
      persistently infected mice were completely identical to those of the control.
      However, the inductive hematopoiesis, examined by the autologous marrow
      reconstitution after 5-fluorouracil administration, was significantly impaired in
      the MCMV persistently infected mice (P < 0.05). In a colony-forming unit-spleen
      assay and a long-term bone marrow culture system, a decreased capacity of bone
      marrow stromal cells to support hematopoiesis was observed in the MCMV-infected
      mice in comparison with the controls. The existence of MCMV DNA in the adherent
      cells of long-term bone marrow culture from the MCMV-infected mice were confirmed
      by a polymerase chain reaction but not in the nonadherent cells. Furthermore, the
      increased expression level of tumor necrosis factor-alpha by stromal cells was
      also observed by semiquantitative reverse transcriptase-polymerase chain
      reaction. These results therefore strongly suggest that MCMV remains to infect
      the stromal cells while also inhibiting inductive hematopoiesis through the
      impairment of the stromal cell functions in the MCMV persistently infected mice.

PMID- 9918874
TI  - Trans-activator Tax of human T-cell leukemia virus type 1 enhances mutation
      frequency of the cellular genome.
AB  - Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a potent trans
      activator of specific sets of target genes, and on the other hand, it is a trans
      repressor of other sets of genes. It is also an inhibitor of the tumor suppressor
      protein p16(INK4a) and thus has been thought to contribute to induction of adult
      T-cell leukemia (ATL). We examined the mutagenic effects of Tax on a cellular
      gene, hypoxanthine guanine phosphoribosyltransferase (hprt), and LacI gene in
      lambda shuttle vector exogenously integrated in Big Blue Rat-2 (BBRat-2) cells.
      Expression of Tax in BBRat-2 cells enhanced the frequency of HPRT(-) phenotype
      severalfold. Tax-expressing cell clones, BBTax-1 and -2 established from BBRat-2
      cells, gave rise to an average mutation frequency of 5.9 x 10(-5) in LacI gene,
      but Tax-negative cell clones, BBRat-C1 and -C2, showed 2. 1 x 10(-5). The 2.8
      fold increase in mutation frequency in the presence of Tax indicates that Tax
      expression enhanced mutation frequency in chromosomal DNA. However, neither the
      mutation spectrum of base transitions, transversions, and deletions/insertions
      nor the loci of the mutations were significantly affected by Tax expression.
      These findings indicate that Tax has the capability to induce random mutations
      and suggest that Tax would be able to modulate cellular phenotypes through
      mutation of the cellular genome.

PMID- 9918875
TI  - Identification of a sequence element involved in AC2-mediated transactivation of
      the pepper huasteco virus coat protein gene.
AB  - The geminivirus AC2 gene product transactivates the expression of the coat and
      movement protein (CP and BV1) genes, and this effect seems to be mediated by
      specific although hitherto unknown cis-acting elements. In this work we examined
      regions from the CP and BV1 gene promoters of pepper huasteco virus (PHV) to
      define the sequence elements involved in regulation by AC2. Results from
      transient gene expression and transgenic plant assays suggest that a truncated
      115-nt CP promoter is still responsive to the viral transactivator. This promoter
      contains three elements similar to a sequence motif termed conserved late element
      (CLE), which is found in the regulatory regions of many geminiviruses and that
      was previously suggested, on a theoretical basis, to be a potential functional
      target for AC2 (Arguello-Astorga et al. (1994), Virology 203, 90-100). To confirm
      these results, an oligonucleotide containing two CLE motifs was synthesized and
      characterized in gain-of-function experiments. Transient expression assays showed
      that this 29-nt sequence is able to confer AC2 responsiveness to heterologous
      promoters. A smaller oligonucleotide (16 nt) containing a single CLE also
      conferred this activity. In addition, when the CLE motifs were mutated in their
      original context (truncated 115-nt promoter), this modified promoter lost its
      ability to be transactivated by AC2. All these results support the involvement,
      at least in the case of PHV, of CLE sequences in the process of transactivation.

PMID- 9918876
TI  - Phenotype of HIV-1 lacking a functional nuclear localization signal in matrix
      protein of gag and Vpr is comparable to wild-type HIV-1 in primary macrophages.
AB  - Human immunodeficiency virus type 1 (HIV-1) is considered to infect nondividing
      cells because nuclear localization signals (NLS) in matrix (MA, p17(Gag)) and Vpr
      allow active nuclear transport of the preintegration complex. Previous studies
      demonstrated that HIV-1 reverse transcription is successful only in cells with
      proliferative potential, thus restricting HIV-1 replication to cycling cells. To
      sort out this apparent discrepancy we compared the phenotype of a chimeric HIV-1
      variant lacking a functional Vpr and MA-NLS (R7. deltaVpr.deltaNLS), and
      previously described to lack replicative capacity in macrophages and growth
      arrested cells, with a chimera lacking a functional Vpr (R7.deltaVpr). Both
      variants replicated efficiently in primary macrophages, with only minimal
      differences in the kinetics of reverse transcription, integration, or p24
      production. In agreement with our previous observation, elongation of reverse
      transcription was restricted to the proliferating subpopulation of macrophages.
      Replication of R7.deltaVpr and R7.deltaVpr.deltaNLS could also be demonstrated in
      aphidicolin-treated macrophages, indicating efficient nuclear transport in G1/S
      phase-arrested cells. In conclusion, our results confirm the dependency of the
      process of HIV-1 reverse transcriptase on cell proliferation in primary
      macrophages and exclude an important role of MA-NLS and Vpr in macrophage
      infection.

PMID- 9918877
TI  - The complete genomic sequence of an HTLV-II isolate from a Guahibo Indian from
      Venezuela.
AB  - A polyclonal CD3(+), CD8(+) T-cell line, G2, was derived from the peripheral
      blood of a seropositive, PCR-positive, HTLV-IIB infected Guahibo Indian from
      Venezuela. The cell line is productively infected with HTLV-IIB. The entire HTLV
      II G2 proviral DNA was sequenced via PCR using overlapping HTLV-II primer pairs.
      Phylogenetic analyses indicate that HTLV-II G2 is the most divergent HTLV-IIB
      strain identified to date. Characterization of its deduced proteins and its
      relationship to other members of the PTLV/BLV genus of retroviruses are
      discussed.

PMID- 9918878
TI  - Conditional cell transformation by doxycycline-controlled expression of the MC29
      v-myc allele.
AB  - To investigate the molecular basis of oncogenesis induced by the v-myc oncogene
      of avian myelocytomatosis virus MC29, we developed a conditional cell
      transformation system in which expression of the MC29 v-myc allele is dependent
      on a doxycycline-sensitive transactivator (tTA). Clonal lines of quail embryo
      fibroblasts transformed by doxycycline-controlled v-myc revert to the normal
      phenotype and lose their ability to grow in soft agar after the addition of
      doxycycline. Repression of v-myc causes the cells to withdraw from the cell
      cycle, and long-term survival in culture requires reexpression of v-myc. Although
      complete repression of v-myc mRNA and v-Myc protein in these cells occurs within
      14 h after the addition of doxycycline, the first morphological alterations are
      observed after 24 h, and after 3 days, the morphology changed entirely from small
      rounded cells showing a typical myc-transformed phenotype to large flat cells
      resembling normal fibroblasts. Cells exposed to doxycycline for 3 days
      reexpressed v-myc within 24 h after withdrawal of the drug from the culture
      medium, partial retransformation occurred after 2 days, and complete
      morphological transformation was reestablished after 6 days. Analogous results
      were obtained with a cell line in which expression of the v-myc allele is
      dependent on a reverse transactivator (rtTA) that is activated by doxycycline.
      The striking differential expression of known transformation-sensitive genes and
      of new candidate v-myc target genes revealed the tightness of the doxycycline
      controlled v-myc expression system. The data also indicate that expression of v
      myc in these cells is indispensable for enhanced proliferation, transformation,
      and immortalization.

PMID- 9918879
TI  - The ORF, regulated synthesis, and persistence-specific variation of influenza C
      viral NS1 protein.
AB  - The open reading frame (ORF) and the regulated synthesis of the influenza C viral
      NS1 protein were analyzed in view of viruses possessing different biological
      activities. We provide evidence for a 246-amino-acid NS1-ORF, encoded by five
      viral strains and variants. Prokaryotic expression of the prototype NS1-ORF
      resulted in a product of 27 kDa, confirming the predicted molecular weight. Using
      an antiserum raised against recombinant NS1 protein, nonstructural proteins of
      wild-type virus were detected in infected cells for a limited course of time,
      whereas a persistent virus variant was characterized by a long-term nonstructural
      gene expression. As examined by infection experiments, the intracellular
      distribution of nonstructural protein was nuclear and cytoplasmic, whereas in NS1
      gene-transfected cells, the cytoplasmic localization occurred in a fine-grained
      structure, suggesting an analogy to influenza A viral NS1 protein. Concerning
      persistent infection, NS1 protein species differing in sizes and
      posttranslational modifications were observed for a persistent virus variant, as
      particularly illustrated by a high degree of NS1 phosphorylation. Virus
      reassortant analyses proved the importance of the NS-coding genomic segment: the
      minimal viral properties required for the establishment of persistence were
      transferred with this segment to a monoreassortant virus. Thus the influenza C
      viral NS1 protein is a 246-amino-acid nuclear-cytoplasmic phosphoprotein that can
      be subject to specific variations being functionally linked to a persistent virus
      phenotype.

PMID- 9918880
TI  - A distal element in the HPV-11 upstream regulatory region contributes to promoter
      repression in basal keratinocytes in squamous epithelium.
AB  - In benign squamous lesions and in organotypic epithelial cultures, the human
      papillomavirus (HPV) E6 and E7 genes are transcriptionally up-regulated in
      differentiated, spinous keratinocytes. We previously identified sequence elements
      in the enhancer-promoter regions of HPV types 18 and 11 important for this
      promoter regulation by using the bacterial LacZ reporter gene in stratified raft
      cultures of primary human keratinocytes (PHKs) or in submerged, proliferating
      cultures acutely transduced with recombinant retroviruses. Notably, mutations in
      the promoter-proximal Sp1, Oct1, and AP1 sites each significantly reduce reporter
      activity in differentiated cells, indicating that the bound factors are
      transcription transactivators. In the present study, we performed further
      mutagenesis on distal motifs in the HPV-11 regulatory region in PHKs in submerged
      and raft cultures. Mutations in an AP2-like site, three individual NF-1 sites, or
      five NF-1 sites collectively reduced promoter activity slightly in differentiated
      cells. A mutation in a putative glucocorticoid response element had no
      discernable effect in the presence or the absence of dexamethasone. However,
      mutations in a C/EBP binding site, especially the distal site, strikingly up
      regulated reporter gene expression, particularly in basal and lower spinous
      cells, implicating bound protein as a transcription repressor. Collectively,
      these results demonstrate that the overall differentiation-dependent
      papillomaviral gene expression observed in vivo and in vitro involves promoter
      repression in the lower strata and activation in the upper, differentiated
      strata.

PMID- 9918881
TI  - Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and
      TAP-1 genes.
AB  - JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and
      JB/MS), express a common melanoma-associated antigen (MAA) encoded by an
      ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express
      the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When
      JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1
      gene, it resulted in the appearance of H-2Kb molecules and an increase in their
      immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized
      by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable
      elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1
      cells. Northern blot analysis showed no differences in ecotropic retroviral
      messages in MelARV-producing and -nonproducing melanoma cells, suggesting that
      loss of MelARV production was not due to down-regulation of MelARV transcription.
      Southern blot analysis revealed several rearrangements in the proviral DNA of H
      2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral
      DNA from these cells showed numerous nucleotide substitutions, some of which
      resulted in the appearance of a novel intraviral PstI restriction site and the
      loss of a HindIII restriction site in the pol region. PCR amplification of the
      proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive
      cells is novel and does not preexist in the parental H-2Kb-negative melanoma
      cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not
      amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of
      retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably
      due to the induction of recombination between a productive ecotropic MelARV and a
      defective nonecotropic provirus leading to the generation of a defective
      ecotropic provirus and the loss of MelARV production and expression of the
      retrovirus-encoded MAA.

PMID- 9918882
TI  - Interferon-beta-induced human immunodeficiency virus resistance in CD34(+) human
      hematopoietic progenitor cells: correlation with a down-regulation of CCR-5
      expression.
AB  - To explore the possibility of conferring a long-term resistance against human
      immunodeficiency virus (HIV) by a low continuous production of interferon-beta
      (IFN-beta) in hematopoietic progenitor cells, we transduced the human CD34(+) TF
      1 cells with a retroviral vector ensuring IFN-beta production. The IFN-beta
      transduction of TF-1 cells resulted in resistance to infection with HIV-LAI, as
      shown by the selective survival of IFN-beta-transduced CD4(+) cells and the
      protection against HIV-induced apoptosis. A similar response against HIV-LAI
      infection was obtained after pretreatment with 100 U/ml of recombinant IFN
      alpha2b or IFN-beta. In contrast, after the addition of macrophage cell tropic (M
      cell-tropic) HIV strain, a treatment with exogenous IFN-alpha2b resulted in a
      >==10-fold lower protection compared with exogenous IFN-beta or IFN-beta
      transduction. This specific effect of IFN-beta on M cell-tropic HIV strains was
      correlated with a down-regulation of the CCR-5 chemokine receptor expression,
      corresponding to a novel antiviral effect of IFN-beta.

PMID- 9918883
TI  - A novel parvovirus isolated from Manchurian chipmunks.
AB  - A novel parvovirus was identified in Manchurian chipmunks inhabiting Korea.
      Hepatitis B surface antigen (HBsAg) was detected in sera from 4 animals among 62
      apparently healthy chipmunks. Electron microscopic examination of the HBsAg
      positive sera revealed virus-like spherical particles 20-22 nm in diameter.
      Extraction of nucleic acid under annealing conditions from the serum samples
      containing virus-like particles yielded a single species of DNA molecule with the
      electrophoretic mobility of 5.6-kb double-stranded DNA. Four overlapping clones
      that encompassed almost the full-length viral genome, except both ends, were
      obtained. By sequencing these clones, we determined the sequence of 5097
      nucleotides of the viral DNA. Two open reading frames were identified, with the
      left side open reading frame encoding a putative nonstructural protein and the
      right side open reading frame encoding a putative capsid protein. The nucleotide
      and amino acid sequences showed significant homology to parvovirus B19 and simian
      parvovirus, but showed little homology to other mammalian autonomous parvoviruses
      or adeno-associated viruses. These observations indicate that the virus isolated
      from Manchurian chipmunks is a novel parvovirus and may be a potentially useful
      animal model of human B19 infection as a new member of the Erythrovirus genus of
      the Parvoviridae.

PMID- 9918884
TI  - Nucleocapsid protein zinc-finger mutants of simian immunodeficiency virus strain
      mne produce virions that are replication defective in vitro and in vivo.
AB  - All retroviruses (except the spumaretroviruses) contain a nucleocapsid (NC)
      protein that encodes one or two copies of the Zn2+-finger sequence -Cys-X2-Cys-X4
      His-X4-Cys-. This region has been shown to be essential for recognition and
      packaging of the genomic RNA during virion particle assembly. Additionally, this
      region has been shown to be involved in early infection events in a wide spectrum
      of retroviruses, including mammalian type C [e.g., murine leukemia virus (MuLV)],
      human immunodeficiency virus type 1 (HIV-1), Rous sarcoma virus, and other
      retroviruses. Mutations in the two Zn2+-fingers of the NC protein of simian
      immunodeficiency virus strain Mne [SIV(Mne)] have been generated. The resulting
      virions contained the normal complement of processed viral proteins with
      densities indistinguishable from wild-type SIV(Mne). All of the mutants had
      electron micrograph morphologies similar to those of immature particles observed
      in wild-type preparations. RNA packaging was less affected by mutations in the NC
      protein of SIV(Mne) than has been observed for similar mutants in the MuLV and
      HIV-1 systems. Nevertheless, in vitro replication of SIV(Mne) NC mutants was
      impaired to levels comparable to those observed for MuLV and HIV-1 NC mutants;
      replication defective NC mutants are typically 10(5)- to 10(6)-fold less
      infectious than similar levels of wild-type virus. One mutant, DeltaCys33-Cys36,
      was also found to be noninfectious in vivo when mutant virus was administered
      intravenously to a pig-tailed macaque. NC mutations can therefore be used to
      generate replication defective virions for candidate vaccines in the SIV macaque
      model for primate lentiviral diseases.

PMID- 9918886
TI  - Movement of hordeivirus hybrids with exchanges in the triple gene block.
AB  - The barley stripe mosaic virus (BSMV) triple gene block (TGB) coding for movement
      proteins (MPs) was replaced with the respective TGB genes from two other
      hordeiviruses, poa semilatent virus (PSLV) or lychnis ringspot virus (LRSV). The
      BSMV/LRSV recombinant did not exhibit infectivity on the plants tested, whereas
      the infection rate and host range of the BSMV/PSLV hybrid were similar to those
      of BSMV. In particular, the BSMV/PSLV hybrid infected Nicotiana benthamiana, a
      nonhost plant for PSLV, indicating a contribution of non-MP elements of BSMV
      genome to host specificity of virus transport. Assuming that the PSLV TGB was
      functional in the BSMV genome context, a further series of recombinants was
      constructed, in which smaller portions of the BSMV TGB were replaced by the
      corresponding PSLV sequences. Examination of the infectivity of the hybrid
      viruses suggested that the TGB-coded proteins could interact in a host-dependent
      manner to mediate cell-to-cell movement. Analysis of recombinants with hybrid
      sequences of the first gene in the TGB (beta b gene) indicated that (i) sequence
      independent binding of beta b to viral RNAs could occur during formation of beta
      b-RNA complexes in vivo, and that (ii) the beta b MP is involved in virus long
      distance movement, for which homologous N- and C-terminal beta b domains are
      required.

PMID- 9918885
TI  - Interaction of the globular domains of pIII protein of filamentous bacteriophage
      fd with the F-pilus of Escherichia coli.
AB  - Gene 3 protein (pIII), a minor coat protein at one end of the filamentous
      bacteriophage fd, is involved in initiating the infection by the virus of
      Escherichia coli cells that display an F-pilus. Infection is thought to start
      with the adsorption of the D2 domain of pIII to the tip of the pilus, retraction
      of the pilus, and penetration of the E. coli cell membrane mediated by an
      interaction between the D1 domain of pIII and the Tol protein complex in the
      membrane. A subgene encoding the pIII-D1D2 di-domain was created, and the subgene
      was successfully overexpressed in E. coli cells. Domains D1 and D2 were separated
      after limited proteolysis of a modified pIII-D1D2 (designated pIII-D1D2.trp) into
      which two tryptic cleavage sites were introduced at appropriate points. The
      purified pIII-D1D2 di-domain and pIII-D2 domain were able to bind to the F-pilus,
      competing with the wild-type pIII and delaying infection by the intact
      filamentous phage. The pIII-D1 domain was unable to bind to the F-pilus by this
      criterion. This provides conclusive evidence that the pIII-D2 domain is
      responsible for the adsorption to the tip of the F-pilus and can achieve this in
      the absence of domain D1, opening the way to identifying the molecular basis of
      the interaction of pIII-D2 with the pilus.

PMID- 9918887
TI  - Stable ubiquitination of the ICP0R protein of herpes simplex virus type 1 during
      productive infection.
AB  - ICP0R is the polypeptide product of an alternatively spliced transcript of the
      gene encoding the transactivator protein ICP0 of herpes simplex virus type 1 (HSV
      1). Although it has been shown to act as a transrepressor of gene expression in
      transfection assays, overexpression of the ICP0R protein in the recombinant virus
      HSV-KST was previously found to have no detectable effect on virus replication,
      so that the role it plays in HSV-1 infection remains unclear. Analysis of HSV-KST
      infected cell lysates by Western blotting revealed the presence of not only the
      41-kDa ICP0R polypeptide but also a 64-kDa processed form of the protein. This
      processing event was the result of ubiquination of the ICP0R protein, as
      demonstrated by the reactivity of the 64-kDa species with antibody specific for
      the influenza virus hemagglutinin (HA) protein epitope in experiments where the
      gene encoding ICP0R was coexpressed with a gene encoding HA-tagged ubiquitin.
      Surprisingly, the 64-kDa form of ICP0R was found to be remarkably stable and
      persisted in infected cells for many hours after processing, despite the fact
      that ubiquitination normally functions as a means of tagging proteins for rapid
      degradation. Analyses of mutant polypeptides containing arginine substitutions at
      each of the lysine residues of ICP0R, which represent potential ubiquitin
      conjugation sites, revealed that a single lysine residue at codon 248 was both
      necessary and sufficient for the appearance of the 64-kDa processed form.
      However, a number of ICP0R mutants that retained the ubiquitination site at
      lysine 248 but contained disruptions of sequences at distant sites also lacked
      detectable 64-kDa protein, indicating that the integrity of the overall structure
      of ICP0R was an additional determinant for ubiquitination.

PMID- 9918889
TI  - Temperature sensitivity of two different steps in the viral life cycle of feline
      immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) multiplication is totally blocked by
      incubation of infected cells at 41 degrees. This inhibition does not take place
      with a thermoresistant strain of FIV, designated m41, indicating the role played
      by the viral genome in temperature sensitivity. We have investigated the steps in
      the life cycle of wild-type FIV that are thermosensitive and found that they
      depend on the host cells infected. In CrFK cells, FIV replication was inhibited
      after the penetration step at 41 degrees. Synthesis of viral RNA and DNA was
      barely detectable and no viral antigen appeared in the extracellular medium.
      Nevertheless, viral multiplication resumed on incubation at 37 degrees,
      suggesting a state of latency at the elevated temperature. In peripheral blood
      mononuclear cells (PBMCs), the FIV cycle was inhibited at 41 degrees after the
      synthesis of viral DNA. Several viral mRNAs failed to appear as fully spliced
      products and no viral antigen was found in the extracellular medium. As in CrFK
      cells, viral multiplication occurred in PBMCs after a shift to the permissive
      temperature. These results suggest that at least two steps in the viral life
      cycle are sensitive to 41 degrees and that two different viral functions of the
      thermoresistant mutant m41 are modified to overcome temperature sensitivity.

PMID- 9918888
TI  - Characterization of early region 1 and pIX of bovine adenovirus-3.
AB  - The mRNAs from early region 1 (E1) and pIX of bovine adenovirus type 3 (BAV-3)
      have been studied by Northern blot, S1 nuclease, and cDNA analysis and
      transcriptional maps for the regions were constructed. The transcriptional map
      for the E1 region of BAV-3 is different from those of mouse and human
      adenoviruses for which transcriptional maps for the regions have been
      constructed. The E1A region of BAV-3 is located between 0.8 and 10.5 map units
      and several different transcripts are produced from the region using alternative
      splice donor sites. The transcripts from the E1A region overlap with those of E1B
      and pIX. In BAV-3, the E1B region maps between 4.2 and 10.5 map units and encodes
      two major mRNA species. The mRNAs of E1B region differ from each other in that
      the smaller mRNA coding for the 157R protein has a large intron removed from a
      region corresponding to the coding region of E1B 420R protein. As in HAVs, the
      E1B 420R protein of BAV-3 could be translated only by internal initiation from
      the larger bicistronic mRNA as there are no transcripts produced exclusively for
      the production of 420R protein. The transcriptional unit of pIX is transcribed
      from an independent promoter and encodes a structural component of the adenovirus
      capsid. To identify and characterize the proteins produced from the region,
      antibodies were raised in rabbits that recognized specific proteins in Western
      blot and immunoprecipitation assays.

PMID- 9918890
TI  - Rice tungro bacilliform virus open reading frame 3 encodes a single 37-kDa coat
      protein.
AB  - Rice tungro bacilliform virus (RTBV) is a plant pararetrovirus and a member of
      the Caulimoviridae family and closely related to viruses in the Badnavirus genus.
      The coat protein of RTBV is part of the large polyprotein encoded by open reading
      frame 3 (ORF3). ORF3 of an RTBV isolate from Malaysia was sequenced (accession
      no. AF076470) and compared with published sequences for the region that encodes
      the coat protein or proteins. Molecular mass of virion proteins was determined by
      mass spectrometry (matrix-assisted laser desorption/ionization-TOF) performed on
      purified virus particles from three RTBV isolates from Malaysia. The N- and C
      terminal amino acid sequences of the coat protein were deduced from the mass
      spectral analysis, leading to the conclusion that purified virions contain a
      single coat protein of 37 kDa. The location of the coat protein domain in ORF3
      was reinforced as a result of immunodetection reactions using antibodies raised
      against six different segments of ORF3 using Western immunoblots after SDS-PAGE
      and isoelectrofocusing of proteins purified from RTBV particles. These studies
      demonstrate that RTBV coat protein is released from the polyprotein as a single
      coat protein of 37 kDa.

PMID- 9918891
TI  - Minimal sequence and structural requirements of a subgenomic RNA promoter for
      turnip crinkle virus.
AB  - Infection of plants or protoplasts with turnip crinkle virus (TCV) results in the
      synthesis of the genomic RNA and two subgenomic (sg) RNAs of 1.7 kb and 1.45 kb,
      respectively. Both of the sgRNA promoters were characterized previously and their
      secondary structures predicted by computer analysis [J. Wang and A. E. Simon
      (1997). Virology 232, 174-186]. Secondary structure-sensitive chemical and
      enzymatic probes have now been used to determine the structure of the promoter
      directing synthesis of the 1.45-kb sgRNA, namely the 1.45-kb sgRNA promoter, in
      solution. The newly obtained structure conforms with the previously predicted
      hairpin structure except for the hairpin base: four CG base pairs and a CA bulge
      are present instead of an A bulge. Studies of deletions within the 96-nucleotide
      (nt) 1.45-kb sgRNA promoter defined a minimal 30-nt core sequence as essential
      for promoter activity: a 21-nt hairpin and a 9-nt flanking single-stranded
      sequence. Mutational analysis in the stem section of the core promoter supported
      a role for the primary sequence and secondary structure in promoter activity.
      Sequence alterations in the flanking single-stranded region further suggest that
      the sequence CCCAUUA, encompassing the transcription start site, is required for
      efficient transcription of the 1.45-kb sgRNA by the TCV RNA-dependent RNA
      polymerase in vivo.

PMID- 9918892
TI  - Sustained elevation of plasma brain natriuretic peptide levels associated with
      progressive ventricular remodelling after acute myocardial infarction.
AB  - Previous studies have shown that levels of plasma brain natriuretic peptide (BNP)
      increase in an early phase of acute myocardial infarction. However, the relations
      between plasma BNP levels and left ventricular remodelling, which occurs long
      after acute myocardial infarction, are not fully understood. Venous plasma BNP
      levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute
      myocardial infarction in 21 patients. Left ventricular end-diastolic volume index
      (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by
      electron-beam computed tomography using Simpson's method. The remodelling group
      (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline
      value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in
      the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained
      elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90
      (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the
      remodelling group. In contrast, plasma BNP levels significantly decreased from
      day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level
      thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated
      positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic
      phase. More importantly, the sustained elevation of plasma BNP (percentage
      decrease smaller than 25%) from day 30 to day 90 identified patients in the
      remodelling group with a sensitivity of 100% and a specificity of 83%. In
      conclusion, not only the high levels of plasma BNP in an acute phase, but also
      the sustained elevation of plasma BNP in a chronic phase, may be associated with
      progressive ventricular remodelling occurring long after acute myocardial
      infarction.

PMID- 9918894
TI  - Heart rate variability in 1-day-old infants born at 4330 m altitude.
AB  - In fetuses and newborn infants heart rate variability changes in conditions of
      acute and chronic hypoxia; we therefore asked whether heart rate variability of
      infants born at high altitude differed from that of low-altitude infants. Short
      term recordings (4-5 min) of inter-beat intervals were obtained in 19 infants in
      Lima (50 m altitude) and in 15 infants in Cerro de Pasco (4330 m, barometric
      pressure approximately 450 mmHg, inspired oxygen pressure approximately 94 mmHg)
      during quiet rest in warm conditions (ambient temperature, Ta, approximately 35
      degrees C). In 12 infants from each group recordings were also obtained during
      cooling (Ta approximately 26 degrees C). Heart rate variability was evaluated
      from 512 consecutive inter-beat intervals, with analysis based on time-domain and
      frequency-domain methods. At warm Ta, heart rate variability did not differ
      between the two groups. During cooling, heart rate increased only in the low
      altitude group. As in the warm, during cooling most parameters of heart rate
      variability did not differ between the two groups. The only exception was the
      inter-beat interval power of the high-frequency range of the spectrum (0.15-0.4
      Hz), which, at least in adults, is believed to be a reflection of vagal activity,
      and was greater in the high-altitude group. It is concluded that gestation at
      high altitude, despite its blunting effects on fetal growth, does not have a
      major impact on heart rate variability of the newborn. Nevertheless, the
      possibility that differences in response to cooling may reflect some limitation
      in heart rate control needs to be examined further.

PMID- 9918893
TI  - Effect of beta-blockade on baroreceptor and autonomic function in heart failure.
AB  - Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart
      failure there is little information on their effects on autonomic and
      baroreceptor function which may have important prognostic implications. We sought
      to determine first whether beta-adrenoreceptor blockade will improve baroreceptor
      function and vagal tone in chronic heart failure, and second whether there were
      any differences between standard therapy with metoprolol and the second
      generation vasodilating beta-blocker celiprolol. In this double-blind randomized
      placebo-controlled study 50 patients with stable chronic heart failure received
      either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12
      weeks after a 4-week dose titration period. Thirty-five healthy normal subjects
      were also studied. Baroreceptor gain was assessed non-invasively by cross
      spectral analysis of R-R and systolic blood pressure low- and high-frequency
      components (the alpha angle) during controlled respiration. High-frequency power
      was used as a measure of vagal modulation. Satisfactory recordings for analysis
      were obtained in 31 patients with heart failure. The results showed that at
      baseline baroreceptor gain (alphaHF) was significantly depressed in patients with
      heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/
      1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor
      gain improved significantly whether measured while supine (P=0.03) or standing
      (P=0.009), and this was associated with a significant increase in R-R HF power
      (P=0. 008). There were no significant changes after treatment with celiprolol or
      placebo. We conclude that metoprolol but not celiprolol therapy restores
      baroreceptor gain towards normal and increases vagal tone in chronic heart
      failure. The ancillary properties of celiprolol do not appear to provide any
      advantages over metoprolol for the restoration of autonomic and baroreceptor
      function in heart failure.

PMID- 9918895
TI  - Altered small artery morphology and reactivity in critical limb ischaemia.
AB  - Although the pathophysiology of critical limb ischaemia is poorly understood,
      there is evidence that the condition of the small arteries may determine the
      outcome of revascularization procedures. This study was designed to investigate
      the effects of critical limb ischaemia on the structure and function of the small
      arteries in the leg. Small arteries (<500 microm) from proximal (non-ischaemic)
      and distal (ischaemic) sites were obtained from patients undergoing bypass
      surgery for critical limb ischaemia and mounted in a myograph. Reactivity and
      morphological measurements were carried out and compared with controls. Control
      vessels from the thigh and calf showed no difference in media to lumen ratio.
      However, a comparison of ischaemic and non-ischaemic vessels from the patients
      with critical limb ischaemia showed significant thinning of the ischaemic vessel
      wall. Contraction studies using noradrenaline and angiotensin II revealed a
      significant decrease in the response of ischaemic vessels compared with the non
      ischaemic vessels from the same patient. Moreover, these differences in
      reactivity were still apparent after the responses were corrected for wall
      thickness. Endothelial function assessed using the endothelium-dependent agonists
      acetylcholine and bradykinin showed a significantly impaired relaxation response
      to acetylcholine but not to bradykinin in the ischaemic vessels, and
      acetylcholine-induced relaxation was not improved after incubation with
      indomethacin. There was no change in the response to the endothelium-independent
      cAMP-mediated vasodilator iloprost but a significant impairment to sodium
      nitroprusside which acts via cGMP. These results suggest that small arteries in
      critical limb ischaemia are altered in both structure and function, with vessel
      wall thinning and impaired responses to acetylcholine and sodium nitroprusside.

PMID- 9918897
TI  - Survival of human carrier erythrocytes in vivo.
AB  - Erythrocytes offer the exciting opportunity of being used as carriers of
      therapeutic agents. Encapsulation within erythrocytes will give the therapeutic
      agent a clearance equivalent to the normal life of the erythrocyte therefore
      maintaining therapeutic blood levels over prolonged periods and also giving a
      sustained delivery to the monocyte-macrophage system (reticulo-endothelial
      system). Both the dose and frequency of therapeutic interventions could thus be
      reduced. Ensuring a near-physiological survival time of carrier erythrocytes is
      essential to their successful use as a sustained drug delivery system, and this
      has not been demonstrated in man. In this study we assessed the survival in vivo
      of autologous unloaded energy-replete carrier erythrocytes in nine volunteers,
      using a standard 51Cr erythrocyte-labelling technique. Within 144 h after
      infusion there was a 3 to 49% fall in circulating labelled cells, followed
      thereafter by an almost complete return to initial circulating levels; surface
      counting demonstrated an initial sequestration of erythrocytes by the spleen and
      subsequent release. Mean cell life and cell half-life of the carrier erythrocytes
      were within the normal range of 89 to 131 days and 19 to 29 days respectively.
      These results demonstrate the viability of carrier erythrocytes as a sustained
      drug delivery system.

PMID- 9918896
TI  - Nitric oxide stimulates cyclic guanosine monophosphate production and
      electrogenic secretion in Caco-2 colonocytes.
AB  - Nitric oxide stimulates intestinal ion transport via the activation of enteric
      nerves, but it is not known whether it regulates intestinal transport function by
      acting on the epithelium directly. The aim of this study was to determine the
      influence of nitric oxide on epithelial electrogenic ion secretion, measured as
      the short-circuit current (Isc), using the human colonic carcinoma cell line Caco
      2. The cellular mechanisms were examined by measuring epithelial cGMP production,
      and nitrite release was monitored as an index of nitric oxide synthesized. The
      nitric oxide substrate L-arginine methyl ester increased nitrite release,
      electrogenic secretion and cell cGMP production. Pretreatment with L-NAME (Nomega
      nitro-L-arginine methyl ester, 1 mM), but not the D-isomer, significantly reduced
      the electrogenic secretion and cGMP production evoked by L-arginine methyl ester,
      implicating nitric oxide synthase involvement. Pretreatment with cystamine, but
      not Methylene Blue, significantly reduced the maximum Isc and the cGMP release
      induced by L-arginine methyl ester and the nitric oxide donor sodium
      nitroprusside, implicating the involvement of particulate guanylate cyclase. In
      conclusion, nitric oxide stimulates electrogenic ion secretion and cGMP
      production in intestinal epithelial cells by activating particulate guanylate
      cyclase. The direct action of nitric oxide on the intestinal epithelium may be
      important in the regulation of intestinal transport function in health and in
      inflammatory bowel disease.

PMID- 9918898
TI  - Increased splanchnic blood flow after hypoglycaemia in diabetic and normal man:
      evidence against glucagon as a mediator.
AB  - Superior mesenteric artery blood flow increases significantly after hypoglycaemia
      in healthy humans. Glucagon has vasoactive properties but its role in
      hypoglycaemic hyperaemia is unclear. To assess this role, we studied the superior
      mesenteric artery blood flow response to hypoglycaemia of patients with
      uncomplicated Type 1 (insulin-dependent) diabetes mellitus of at least 10 years
      duration; a group known to have defective glucagon response to hypoglycaemia.
      Hypoglycaemia was induced using an intravenous infusion of soluble human insulin
      (2.5 m-units.min-1.kg-1) discontinued at a plasma glucose of 2.5 mmol/l. Superior
      mesenteric artery blood flow was measured using transcutaneous duplex Doppler
      ultrasound. Plasma samples were assayed for glucose, insulin, glucagon,
      catecholamines, growth hormone and cortisol. Plasma glucose concentration fell to
      a nadir of 1.8 (0.3) mmol/l in patients and 1.4 (0.1) mmol/l in controls. Plasma
      glucagon concentration was unchanged in patients from a baseline level of 111.7
      (13.1) ng/l but rose in controls from 105 (8.5) to a peak of 239 (3.1) ng/l
      (P<0.001). Superior mesenteric artery blood flow increased in both groups: from
      385 (29) to 921 (100) ml/min (140% increase; P<0.05) in patients and from 517
      (50) to 790 (67) (53% increase; P<0.001) in controls. This study shows that
      patients with Type 1 diabetes have a normal splanchnic vascular hyperaemic
      response to hypoglycaemia despite defective glucagon counter-regulation. These
      results support our previous work suggesting that glucagon is not a major
      mediator of this response; it seems likely that circulating adrenaline is the
      major regulatory mechanism.

PMID- 9918899
TI  - Change in tissue concentrations of lipid hydroperoxides, vitamin C and vitamin E
      in rats with streptozotocin-induced diabetes.
AB  - The tissue concentration of lipid hydroperoxides, which was determined by a
      specific method involving chemical derivatization and HPLC, increased
      significantly in the heart, liver, kidney and muscle of diabetic rats 8 weeks
      after the intraperitoneal injection of streptozotocin compared with that of the
      control group. These results demonstrate that an enhanced oxidative stress is
      caused in these tissues by diabetes. Vitamin C concentrations of the brain,
      heart, lung, liver, kidney and plasma of the diabetic rats decreased
      significantly after 8 weeks compared with those of the control group. Vitamin E
      concentrations of the brain, heart, liver, kidney, muscle and plasma of the
      diabetic rats increased significantly after 4 weeks compared with the control
      group. After 8 weeks, an elevation in vitamin E concentration was observed in the
      heart, liver, muscle and plasma of the diabetic rats.

PMID- 9918900
TI  - Human obesity is associated with a chronic elevation in brain 5-hydroxytryptamine
      turnover.
AB  - The afferent signals that evoke changes in energy intake with regard to body
      weight regulation are presumed to arise partly from body stores, with the most
      likely candidate being adipose tissue depots. However, clinical investigation of
      the neuronal circuitry involved in the central nervous system's processing of
      such satiety signals remains largely unexplored. Using percutaneously placed
      catheters in either the right or left internal jugular veins, we were able to
      quantify the release of central nervous system monoamine and indoleamine
      neurotransmitters in 64 weight-stable male subjects with varying degrees of
      adiposity. Veno-arterial plasma concentration differences and internal jugular
      blood or plasma flow were used, according to the Fick Principle, to quantify the
      amount of neurotransmitter stemming from the brain. By combining this technique
      with a noradrenaline and adrenaline isotope dilution method for examining
      neuronal transmitter release, we were able to examine the association between
      central nervous system neurotransmitters and efferent sympathetic nervous outflow
      and adrenomedullary function in human obesity. We found that brain 5
      hydroxytryptamine (serotonin) turnover is chronically elevated in proportion to
      adiposity and is increased postprandially to a similar degree in lean and obese
      individuals. There was no difference in the degree of sympathetic nervous
      activity or rate of adrenaline secretion in the subjects examined. It therefore
      seems that in human obesity, in the face of a chronic elevation in peripheral
      satiety signals, brain serotonergic processes are switched on accordingly, but
      the subsequent physiological response involving a reduction in food intake,
      increased thermogenesis and sympathetic activity is in some way impeded.

PMID- 9918901
TI  - Pharmacokinetics of L-arginine during chronic administration to patients with
      hypercholesterolaemia.
AB  - Acute administration of L-arginine, the precursor of endothelial nitric oxide,
      has been shown to improve endothelial function in hypercholesterolaemic rabbits
      and humans. Animal studies suggest that this beneficial effect, which is thought
      to be related to the increased availability of nitric oxide, may not be sustained
      during chronic oral administration. Pharmacokinetic alterations may contribute to
      this observation. The present study was designed to examine the disposition of L
      arginine in hypercholesterolaemic subjects during long-term administration.
      Plasma L-arginine concentrations were determined by HPLC in 10 patients (eight
      women and two men; mean age 46+/-16 years) after an intravenous dose of 10 or 30
      g and an oral dose of 5 or 7 g. Pharmacokinetic studies were performed at regular
      intervals (4 weeks) during a 12-week period of oral L-arginine administration (14
      21 g/day). The average plasma L-arginine concentrations before (baseline) and
      during administration were 16.1+/-1.2 and 22.5+/-1.3 microg/ml respectively
      (P<0.05). Plasma concentrations of L-arginine remained above baseline throughout
      weeks 2-12. The L-arginine exposure, expressed as a normalized area-under-the
      curve for 8 h (AUC0-8) after oral or intravenous doses during the first visit,
      was 894.4+/-118.7 and 1837. 8+/-157.0 units respectively. There were no
      significant changes in peak plasma L-arginine concentrations or in the AUC0-8
      after oral and intravenous doses during subsequent visits (P>0.05). The mean non
      renal clearance of L-arginine during the four visits remained constant. Knowledge
      of the pharmacokinetics of L-arginine may be useful in the design of clinical
      trials involving this agent, as well as in the interpretation of the
      pharmacodynamics of this important precursor of nitric oxide.

PMID- 9918902
TI  - Isoaspartyl bond formation within N-terminal sequences of collagen type I:
      implications for their use as markers of collagen degradation.
AB  - An ELISA was developed for the measurement of N-telopeptides of the alpha2(I)
      collagen chain containing an isomerized Asp-Gly bond (beta-peptide) using
      polyclonal antibodies raised against the synthetic peptide. The presence of this
      isomerized form in bone was confirmed by positive immunostaining of sections from
      human femoral head. The ELISA was used to measure isomerized peptide in both
      human bone digests and urine samples, showing that an isoaspartyl rearrangement
      occurs in the Asp-Gly sequence at the N-terminus of the alpha2(I) chain in an
      analogous fashion to that found in the C-terminal telopeptide of the alpha1(I)
      chain of collagen. Using this assay in conjunction with a monoclonal antibody
      ELISA to the non-isomerized alpha2(I) N-telopeptide (alpha-peptide), ratios of
      isomerized to normal peptides were estimated in the bone and urine samples.
      Urinary alpha2(I) N-telopeptides showed a higher degree of isomerization than the
      peptides derived from a human bone digest. This is possibly due to relative
      enrichment of the isoaspartyl-bonded peptide during metabolic processing due to
      the proximity of the isoaspartyl bond to a cross-link site. Urinary
      concentrations of isomerized and normal peptides were determined in normal
      adults, children, post-menopausal control subjects and subjects with
      osteoporosis. A lower ratio of beta-peptide to alpha-peptide was observed in
      children's urine, indicative of a higher rate of bone metabolism allowing less
      time for the isomerization to occur. No significant differences were found
      between the post-menopausal control and osteoporotic populations although the
      trends observed supported the hypothesis that a lower degree of isomerization may
      be associated with faster bone turnover.

PMID- 9918903
TI  - Acute hypertension impairs endothelium-dependent vasodilatation.

PMID- 9918904
TI  - Acute carbon tetrachloride feeding selectively damages large, but not small,
      cholangiocytes from normal rat liver.
AB  - The aim of this study was to develop a model of selective duct damage restricted
      to hormone-responsive segments corresponding to the ducts damaged in primary
      biliary cirrhosis (PBC). Carbon tetrachloride (CCl4) was fed by gavage to rats,
      and 2, 7, 14, and 28 days later, small and large cholangiocytes were isolated.
      Apoptosis was determined in situ by morphology and in purified cholangiocytes by
      assessment of nuclear fragmentation by 4, 6-diamidino-2-phenylindole (DAPI)
      staining. Cholangiocyte proliferation was evaluated in situ by morphometry of
      liver sections stained for cytokeratin-19 (CK-19) and by proliferating cellular
      nuclear antigen (PCNA) staining in liver sections and in purified cholangiocytes
      by PCNA gene expression. Ductal secretion was assessed by measurement of secretin
      receptor (SR) gene expression and secretin-induced cyclic adenosine 3',5'
      monophosphate (cAMP) synthesis and secretin-induced choleresis. Two days after
      CCl4 administration, there was an increased number of small ducts, but a
      reduction of large ducts. Apoptosis, observed only in large ducts, was associated
      with decreased DNA synthesis and ductal secretion. Conversely, small
      cholangiocytes expressed de novo the SR gene and secretin-stimulated cAMP
      synthesis 2 days after CCl4 treatment. Proliferation of large cholangiocytes was
      delayed until 7 days, which was associated with a transient increase in ductal
      secretion in vivo. CCl4 effects on cholangiocytes were reversed by day 28. CCl4
      treatment causes a decrease in large duct mass as a result of a higher rate of
      apoptosis and absence of initial proliferation in large cholangiocytes. These
      processes were concomitant with a decrease of ductal secretion in large
      cholangiocytes. Small cholangiocytes appear resistant to CCl4-induced apoptosis,
      and proliferate and transiently compensate for loss of proliferative and
      secretory activity of large cholangiocytes.

PMID- 9918905
TI  - Differences in the metabolism and disposition of ursodeoxycholic acid and of its
      taurine-conjugated species in patients with primary biliary cirrhosis.
AB  - The clinical effectiveness of ursodeoxycholate in the treatment of liver disease
      may be limited by its poor absorption and extensive biotransformation. Because in
      vitro and in vivo studies suggest that the more hydrophilic bile acid
      tauroursodeoxycholate has greater beneficial effects than ursodeoxycholate, we
      have compared for the first time the absorption, metabolism, and clinical
      responses to these bile acids in patients with primary biliary cirrhosis (PBC).
      Twelve female patients with PBC were sequentially administered
      tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months) in a
      randomized, cross-over study. Bile acids were measured in serum, duodenal bile,
      urine, and feces by gas chromatography-mass spectrometry (GC-MS). Biliary
      ursodeoxycholate enrichment was higher during tauroursodeoxycholate
      administration (32.6% vs. 29.2% during ursodeoxycholate; P <.05). Lithocholic
      acid concentration was consistently higher in all biological fluids during
      ursodeoxycholate administration. Fecal bile acid excretion was the major route of
      elimination of both bile acids; ursodeoxycholate accounted for 8% and 23% of the
      total fecal bile acids during tauroursodeoxycholate and ursodeoxycholate
      administration, respectively (P <.05). Tauroursodeoxycholate was better absorbed
      than ursodeoxycholate, and, although it was partially deconjugated and
      reconjugated with glycine, it underwent reduced biotransformation to more
      hydrophobic metabolites. This comparative study suggests that
      tauroursodeoxycholate has significant advantages over ursodeoxycholate that may
      be of benefit for long-term therapy in PBC.

PMID- 9918907
TI  - Effect of losartan, an angiotensin II receptor antagonist, on portal pressure in
      cirrhosis.
AB  - Administration of angiotensin II causes an increase in portal pressure, and
      plasma concentration of angiotensin II is elevated in patients with cirrhosis,
      suggesting that angiotensin II may be involved in the pathogenesis of portal
      hypertension in cirrhosis. We evaluated the effect of the orally active
      angiotensin II receptor antagonist, losartan, on portal pressure in patients with
      cirrhosis and portal hypertension. Thirty patients with severe (hepatic venous
      pressure gradient [HVPG] >/= 20 mm Hg) and 15 patients with moderate (HVPG < 20
      mm Hg) portal hypertension at baseline measurement were treated with an oral dose
      of 25 mg losartan once daily for 1 week and compared with 15 (HVPG >/= 20 mm Hg)
      and 10 (HVPG < 20 mm Hg), respectively, cirrhotic controls. On the seventh day,
      HVPG was determined again, and blood pressure, heart rate, body weight, and
      parameters of liver and kidney function were recorded. Losartan induced a
      significant (P <.001) decrease of HVPG in the patients with severe (-46.8% +/-
      15.5%) and moderate (-44.1% +/- 14.7%) portal hypertension, while no significant
      change was seen in the controls. Losartan caused a slight but significant (P
      <.01) fall in mean arterial blood pressure (-3.1 +/- 5.0 and -3.5 +/- 4.3 mm Hg,
      respectively). One patient treated with losartan had a short symptomatic
      hypotensive reaction after the first dose of losartan that did not recur despite
      continued treatment. No deterioration of liver or kidney function was observed.
      The present study indicates that angiotensin II blockade with orally administered
      losartan is safe and highly effective in the treatment of portal hypertension.

PMID- 9918906
TI  - Association of diabetes mellitus and chronic hepatitis C virus infection.
AB  - While patients with liver disease are known to have a higher prevalence of
      glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV)
      infection may be an additional risk factor for the development of diabetes
      mellitus. To further study the correlation of HCV infection and diabetes, we
      performed a retrospective analysis of 1,117 patients with chronic viral hepatitis
      and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV
      infection, and cirrhosis were independently associated with diabetes. In
      addition, a case-control study was conducted to determine the seroprevalence of
      HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for
      thyroid disease. In the former study after the exclusion of patients with
      conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV
      infected patients compared with 12% of HBV-infected subjects (P =.0004).
      Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were
      independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were
      found to be infected with HCV compared with 1.6% of control patients (P =.02).
      HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus
      3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a
      relatively strong association between HCV infection and diabetes, because
      diabetics have an increased frequency of HCV infection, particularly with
      genotype 2a. Furthermore, it is possible that HCV infection may serve as an
      additional risk factor for the development of diabetes, beyond that attributable
      to chronic liver disease alone.

PMID- 9918908
TI  - Brain histamine levels and neocortical slow-wave activity in rats with portacaval
      anastomosis.
AB  - To determine whether the increased histamine levels in the brain of rats with
      portacaval anastomosis (PCA) are associated with the development of sleep
      disturbances during the light phase, the neocortical slow-wave activity of PCA
      operated rats was examined with electroencephalography (EEG) 1 month and 6 months
      after the surgery. The tissue levels of histamine, tele-methylhistamine, 5
      hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-acetic acid (5-HIAA)
      in frontal cortex were assayed by high-performance liquid chromatography 6 months
      after the surgery. PCA surgery led to changes in the synchronized, low-frequency,
      high-amplitude frontal cortex EEG activity recorded during the light phase. Delta
      wave amplitude but not delta time was significantly decreased, whereas both
      spindle amplitude and spindling time were significantly decreased. There were
      also significant age-related changes, presented as increases in the duration of
      spindles and the amplitude of both delta waves and spindles. PCA-operated rats
      showed a change in the pattern of EEG activity with increasing age similar to
      sham-operated rats. This suggests that once established, the resetting of the
      systems regulating the sleep-waking behavior is being maintained with time. The
      tissue levels of both histamine and metabolite in the frontal cortex were
      increased, whereas the serotonin system showed only an increase in the level of
      the metabolite. There was a significant negative correlation between the
      spindling time and the tissue histamine levels. We suggest that histamine, which
      participates in the control of vigilance, sleep, and wakefulness, as well as in
      the modulation of circadian rhythmicity, may play a role in the development of
      sleep disturbances in rats with PCA.

PMID- 9918909
TI  - Hepatic blood flow and splanchnic oxygen consumption in patients with liver
      failure. Effect of high-volume plasmapheresis.
AB  - Liver failure represents a major therapeutic challenge, and yet basic
      pathophysiological questions about hepatic perfusion and oxygenation in this
      condition have been poorly investigated. In this study, hepatic blood flow (HBF)
      and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were
      assessed in patients with liver failure defined as hepatic encephalopathy grade
      II or more. Measurements were repeated after high-volume plasmapheresis (HVP)
      with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant
      infusion of D-sorbitol and calculated according to Fick's principle from
      peripheral artery and hepatic vein concentrations. In 14 patients with acute
      liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min)
      were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P
      <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic
      liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3
      mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36
      L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased
      from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32
      to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with
      ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2
      L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic
      vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm
      5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD,
      neither systemic nor splanchnic vascular resistance was affected by HVP, but as
      cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more
      blood was directed to the splanchnic region. In all liver failure patients
      treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was
      unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP.
      Changes of ET-1 were positively correlated with changes in HBF (P <.005) and
      VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and
      oxygenation. ET-3 was negatively correlated with systemic vascular resistance
      index before HVP (P <.05) but changes during HVP did not correlate. Our data
      suggest that liver failure is associated with increased HBF and VO2, sp. HVP
      further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that
      splanchnic hypoxia was not present.

PMID- 9918910
TI  - Quality of life before and after liver transplantation for cholestatic liver
      disease.
AB  - Liver transplantation (LT) is an established therapy for patients with end-stage
      primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this
      report, we describe the health status and quality of life (QOL) in patients with
      these cholestatic liver diseases before and after LT. A QOL questionnaire was
      completed by 157 adult patients with PBC or PSC before and 1 year after liver
      transplantation at the Mayo Clinic or Baylor University Medical Center. This
      questionnaire measured four aspects of QOL, including symptoms; physical, social,
      and emotional functioning; health perceptions; and overall QOL. Changes in these
      QOL parameters before and after LT were described, and regression analysis was
      used to assess the relationships between clinical and QOL factors. There were no
      differences in QOL parameters between patients with PBC and PSC. QOL following
      transplantation was substantially better than before transplantation. This was
      observed in all four aspects of QOL. The degree of improvement as measured by
      effect size (difference in mean scores divided by the pretransplantation standard
      deviation) was 0.53 for symptoms (P <.01), 1.16 for function (P <.01), 2.37 for
      health satisfaction (P <.01), and 1.16 for overall QOL (P <.01). Patients'
      overall QOL before transplantation was significantly related to subjective and
      objective health status indicators and clinical factors such as ascites and renal
      dysfunction. QOL at 1-year follow-up, however, could not be adequately predicted
      by the pretransplantation subjective health status and clinical factors. Patients
      with end-stage cholestatic disease undergoing LT experience substantial
      improvement in all aspects of QOL addressed in this study. The patients' QOL 1
      year after LT could not be predicted by pretransplantation variables used in this
      study.

PMID- 9918911
TI  - A model to predict survival following liver retransplantation.
AB  - In the current era of critical-organ shortage, one of the most controversial
      questions facing transplantation teams is whether hepatic retransplantation,
      which has historically been associated with increased resource utilization and
      diminished survival, should be offered to a patient whose first allograft is
      failing. Retransplantation effectively denies access to orthotopic liver
      transplantation (OLT) to another candidate and further depletes an already
      limited organ supply. The study group was comprised of 1,356 adults undergoing
      hepatic retransplantation in the United States between 1990 and 1996 as reported
      to the United Network for Organ Sharing (UNOS). We analyzed numerous donor and
      recipient variables and created Cox proportional-hazards models on 900 randomly
      chosen patients, validating the results on the remaining cohort. Five variables
      consistently provided significant predictive power and made up the final model:
      age, bilirubin, creatinine, UNOS status, and cause of graft failure. Although
      both hepatitis C seropositivity and donor age were significant by univariate and
      multivariate analyses, neither contributed independently to the estimation of
      prognosis when added to the final model. The final model was highly predictive of
      survival (whole model chi2 = 139.63). The risk scores for individual patients
      were calculated, and patients were assigned into low-, medium-, and high-risk
      groups (P <.00001). The low degree of uncertainty in the probability estimates as
      reflected by confidence intervals, even in our high-risk patients, underscores
      the applicability of our model as an adjunct to clinical judgment. We have
      developed and validated a model that uses five readily accessible "bedside"
      variables to accurately predict survival in patients undergoing liver
      retransplantation.

PMID- 9918912
TI  - Altered Gq/G11 guanine nucleotide regulatory protein expression in a rat model of
      hepatocellular carcinoma: role in mitogenesis.
AB  - Guanine nucleotide regulatory proteins (G-proteins) represent an important
      transmembrane pathway whereby extra-cellular signals are transduced to
      intracellular signaling pathways. The mitogen-activated protein kinase (MAPK)
      cascade has been identified as a key factor in transducing numerous mitogenic
      stimuli. MAPK activity is regulated via numerous receptor types, including those
      linked to Gq/G11-proteins, which regulate phospholipase-C activity. We
      hypothesized that alterations in a Gq/G11-PLC pathway may contribute to the
      enhanced cellular mitogenesis characteristic of hepatocellular carcinoma (HCC),
      possibly via a MAPK-dependent pathway. By using an in vivo model of HCC we
      investigated changes in Gq/G11-protein expression in tumorigenic tissue versus
      adjacent, non-neoplastic liver. In addition we addressed the role of Gq/G11
      proteins in the regulation of MAPK-linked mitogenesis by using rat hepatic
      tumorigenic cells (H4IIE) and isolated hepatocytes in culture. Western blot
      analysis showed significant increases in Gqalpha and G11alpha expression in
      tumorigenic liver versus normal liver specimens, an effect that was augmented in
      cultured H4IIE cells versus isolated cultured hepatocytes. Furthermore,
      phosphoinositol specific phospholipase-C (PLC) activity was significantly
      increased in HCC versus normal liver. A specific PLC inhibitor (Et-18-OCH3)
      caused a dose-dependent decrease in serum stimulated DNA synthesis in both
      cultured H4IIE cells and isolated rat hepatocytes, the H4IIE cell line showing
      greater sensitivity to Et-18-OCH3. In addition, serum-stimulated MAPK activity
      was significantly enhanced in H4IIE versus cultured hepatocytes. Moreover,
      treatment with Et-18-OCH3 significantly attenuated serum stimulated MAPK activity
      in both cultured hepatocytes and H4IIE cells. Furthermore, U73122 (Gqalpha-PLC
      specific uncoupler) and GP2A (Gqalpha specific inhibitor) mirrored the effects of
      those observed for Et-18-OCH3 whereas PD98059 (specific MEK inhibitor) completely
      abolished serum-stimulated DNA synthesis in tumorigenic H4IIE cells. We conclude
      that HCC is associated with enhanced Gq/G11-PLC expression/activity as compared
      with normal liver. Furthermore, a PLC-linked MAPK cascade plays a significant
      role in the progression of the enhanced mitogenesis characteristic of HCC.

PMID- 9918913
TI  - Reduced C-terminal Src kinase (Csk) activities in hepatocellular carcinoma.
AB  - The proto-oncogene product pp60(c-src) is the cellular homologue of the Rous
      sarcoma transforming gene, and it is a non-receptor-linked and membrane
      associated tyrosine kinase. There is a close correlation between elevated pp60(c
      src) activity and cell transformation. We have recently reported that pp60(c-src)
      was activated in hepatocellular carcinoma (HCC) of human and Long-Evans cinnamon
      (LEC) rats. However, the mechanisms involved in this process remain unknown. C
      terminal Src kinase (Csk) is a novel cytoplasmic protein tyrosine kinase that
      inactivates the members of the Src family protein tyrosine kinase in vitro. We
      investigated the role of Csk in hepatocarcinogenesis by analyzing the location,
      amount of Csk, and its kinase activity levels in nontumorous cirrhotic and
      tumorous sections of HCC of patients and an animal model of LEC rats. Csk
      tyrosine kinase activity was significantly reduced in tumorous tissues compared
      with nontumorous sections of patients as well as LEC rats. A single
      immunoreactive band at 50 kd was detected with Csk antibody in normal liver (NL),
      chronic hepatitis (CH), and nontumorous cirrhotic (NTC) segments of HCC of
      patients and LEC rats. In human tumorous tissues, Western blot revealed a 53-kd
      immunoreactive band, which was slightly larger than the usual 50-kd band of Csk.
      These results suggest that the reduced activity of tyrosine kinase of Csk may
      play an important role in the malignant transformation of hepatocytes in human
      and LEC rat, and the appearance of 53-kd Csk-related protein may be closely
      involved in the progression of cirrhosis to HCC in humans, and that 50-kd Csk may
      act as an antioncogene through the negative regulation of pp60(c-src) in the
      development of human HCC.

PMID- 9918914
TI  - Activation of cdk4 and cdk2 during rat liver regeneration is associated with
      intranuclear rearrangements of cyclin-cdk complexes.
AB  - Partial hepatectomy (PH) triggers the entry of rat liver cells into the cell
      cycle. The signals leading to cell-cycle activation converge into a family of
      kinases named cyclin-dependent kinases (cdks). Specific cyclin-cdk complexes are
      sequentially activated during the cell cycle. Cyclin D-cdk4 and cyclin E-cdk2 are
      activated during the G1 phase, cyclin A-cdk2 is activated during the S phase, and
      cyclin B-cdk1 during mitosis. In the present study, we have examined the timing
      of the activation of cdk4 and cdk2, the intracellular location of G1/S cyclins
      and cdks, and the relationship between location and cdk4 and cdk2 activities
      during rat liver regeneration after a PH. Results showed that the activity of
      both kinases started at 13 hours and showed maximal levels at 24 hours after
      hepatectomy. In quiescent cells, cyclin D3 and cdk4 were cytoplasmatic, whereas
      cyclin D1 was nuclear. At 5 hours after hepatectomy, cyclin D3 and cdk4 began to
      move into the nucleus, and at 13 hours, they were mostly nuclear. During the
      first 13 hours after hepatectomy, significant amounts of cyclin D1-cdk4 and
      cyclin D3-cdk4 complexes were formed, but they were mostly inactive. At 24 hours,
      these complexes were maximally activated. This activation was associated with the
      accumulation of cyclin D1, cyclin D3, and cdk4 in a nuclear subfraction
      extractable with nucleases. At 28 hours, the activity of cdk4 in this nuclear
      subfraction decreased when cyclin D1 moved from this fraction to the nuclear
      matrix (NM) and the levels of cyclin D3 diminished. The maximal activation of
      cdk2 at 24 hours was also associated with the accumulation of cyclin E, cyclin A,
      and cdk2 in this nuclease-sensitive fraction. The inactivation of cdk2 at 28
      hours was associated with a strong decrease in cdk2 in this nuclear subfraction.
      Thus, results reported here indicate that the activation of cdk4 and cdk2
      observed in rat liver cells after a PH is associated with a specific intranuclear
      location of these cdks and their associated cyclins.

PMID- 9918915
TI  - Expression of vascular endothelial growth factor promotes colonization,
      vascularization, and growth of transplanted hepatic tissues in the mouse.
AB  - A complex vascular network forms an important component of the liver
      architecture. This network is essential for the supply of oxygen and nutrients to
      cells and delivery of molecules for metabolic exchange. In this study, we
      attempted to construct a vascular network in transplanted hepatic tissues and
      examined the effect of such network on tissue formation. Primary hepatocytes of
      adult mice were transfected with vascular endothelial growth factor (VEGF) gene
      in vitro then transplanted with collagen beads intraperitoneally in mice. VEGF
      transfected hepatocytes secreted sufficient protein of the transgene in vitro to
      induce proliferation of endothelial cells. In vivo, VEGF-transfected hepatocytes
      formed a large number of colonies and developed a significant vascular network in
      established tissues compared with control tissues. In addition, hepatocytes of
      VEGF-transfected, established tissues proliferated and formed a substantial
      parenchymal region. These hepatocytes were also functional as confirmed by the
      production of albumin. Our results suggested that VEGF expression conferred not
      only the formation of a vascular network but also promoted tissue formation. Our
      study showed that ex vivo gene transfection into hepatocytes is a useful method
      for the induction of liver reconstitution in vivo.

PMID- 9918916
TI  - Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial
      hepatectomy.
AB  - Recently, it was shown that hepatocyte DNA synthesis after partial hepatectomy
      (PH) is impaired in interleukin-6-deficient (IL-6(-/-)) mice, which results in
      significantly delayed, but eventual, recovery of normal liver weight, compared
      with the IL-6(+/+) controls. Four possible compensatory mechanisms might explain
      this phenomenon: 1) hepatocyte hypertrophy; 2) activation of the oval cell
      compartment and subsequent maturation to hepatocytes; 3) non-oval biliary
      epithelial cell (BEC) proliferation; and/or 4) differential rates of apoptotic
      cell death in the regenerating liver. These hypotheses were tested by subjecting
      IL-6(-/-) and IL-6(+/+) mice to PH and determining sequential liver weight,
      histology, hepatocyte and BEC 5'-bromo-2'-deoxyuridine (BrdU) labeling, liver DNA
      content, alpha-fetoprotein (AFP) mRNA production, and apoptosis at several time
      points after PH. Consistent with previous studies, we show that the absence of IL
      6 significantly impairs hepatocyte DNA synthesis and delays liver weight recovery
      after PH, but the defect observed in this study is less severe than that
      previously reported, and no excess mortality, massive necrosis on histology, nor
      differences in liver injury test are seen. Interestingly, the IL-6(-/-) mice show
      more hepatocyte BrdU pulse labeling than the IL-6(+/+) controls at 24 hours, but
      less at 36, 48, and 60 hours. Continuous BrdU infusion up to 60 hours after PH
      showed a cumulative hepatocyte labeling index of 79.5% in IL-6(+/+) mice and
      70.8% in IL-6(-/-) mice, respectively (P <.03). However, despite a lower labeling
      index and significantly delayed weight recovery, hepatic mass was equally
      restored in the two groups by 96 hours. There was no evidence of oval cell
      proliferation in the IL-6(-/-) mice, as determined by routine histology and AFP
      mRNA analysis, and non-oval BEC proliferation was also slightly impaired in the
      IL-6(-/-) mice compared with the IL-6(+/+) mice. In addition, liver DNA content
      per gram of liver showed an increase compared with normal at 60 hours in both
      groups, but by 96 hours, there was no difference between the two groups. Thus,
      neither oval cell nor BEC proliferation, nor hepatocyte hypertrophy, could
      account for the eventual equivalent weight recovery. There was, however, a
      difference between the two groups in the rate of apoptosis. In normal livers of
      both IL-6(-/-) and IL-6(+/+) mice, apoptotic cells were uncommon, and even fewer
      such cells were detected at 24, 36, and 48 hours after PH. Between 60 and 96
      hours after PH, a wave of apoptosis spread through the livers of both groups. The
      number of apoptotic cells was directly proportional to the magnitude of
      hepatocyte BrdU labeling and liver DNA content after PH, and the difference
      between the nadir of apoptosis at 24 hours and the peak at 96 hours was greater
      for the IL-6(+/+) mice. In addition, a direct comparison between the two groups
      at 96 hours showed that hepatocyte apoptosis was significantly lower in the IL-6(
      /-) versus the IL-6(+/+) mice (P <. 02). Treatment of the IL-6(-/-) mice with rIL
      6 completely reversed the hepatocyte proliferation defect and increased the
      subsequent level of total apoptotic bodies. The fine control of liver weight
      recovery during regeneration after PH is a complex process that involves both
      mitosis and apoptosis. IL-6 affects this process by recruiting, and possibly
      synchronizing, the entry of hepatocytes into cell cycling, which quickly restores
      liver mass. However, this robust response generates superfluous hepatocytes,
      which are eliminated via apoptosis, similar to many other processes involving
      organ growth.

PMID- 9918917
TI  - Enhanced Gi-protein-mediated mitogenesis following chronic ethanol exposure in a
      rat model of experimental hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is associated with increased expression and
      function of inhibitory guanine nucleotide regulatory proteins (Gi-proteins). This
      study addresses the effects of chronic ethanol exposure on the expression and
      function of adenylyl cyclase (AC)-linked G-proteins (Gs and Gi) and growth in
      experimental HCC. G-protein expression and function was determined by immunoblot
      in the hepatic tumorigenic H4IIE cell line and isolated cultured hepatocytes in
      the absence or presence of ethanol (5-100 mmol/L). Chronic exposure (24 hours) to
      ethanol dose-dependently increased Gialpha1/2 expression in the H4IIE cell line,
      but not in cultured hepatocytes. Gsalpha-protein expression remained unchanged in
      both H4IIE cells and cultured hepatocytes following ethanol treatment. In
      addition, ethanol directly activated a Gi-protein, because pertussis toxin (PTx)
      catalyzed, adenosine diphosphate (ADP)-dependent ribosylation of Gialpha
      substrates decreased following ethanol treatment. The increased functional
      activity of Gialpha1/2-protein expression was confirmed by demonstrating that
      ethanol dose-dependently inhibited basal and stimulated AC activity in H4IIE
      cells, while not significantly altering basal AC activity in isolated cultured
      hepatocytes. Furthermore, while ethanol had no significant effect on basal
      mitogenesis in H4IIE cells or hepatocytes, increased mitogenesis caused by direct
      Gialpha-protein stimulation (mastoparan M7; 10-5,000 nmol/L) was further enhanced
      in the presence of ethanol, an effect that was completely blocked following Gi
      protein inhibition (PTx; 100 ng/mL). In contrast, activation of Gi-proteins using
      M7 failed to alter cellular mitogenesis in isolated cultured hepatocytes, whether
      in the absence or presence of ethanol. Finally, analysis of mitogen-activated
      protein kinase (MAPK) activity demonstrated that chronic ethanol treatment
      further enhanced Gi-protein-stimulated MAPK activity in hepatic tumorigenic
      cells. In conclusion, these data demonstrate that ethanol enhances cellular
      mitogenesis in experimental HCC as a result of, at least in part, a Gi-MAPK
      dependent pathway. Furthermore, this effect may be caused by ethanol's direct up
      regulation of the expression and activity of Gi-proteins in HCC.

PMID- 9918918
TI  - Expression of inducible nitric oxide synthase in endotoxemic rat hepatocytes is
      dependent on the cellular glutathione status.
AB  - The inducible nitric oxide synthase (iNOS) promoter contains nuclear factor
      kappaB (NF-kappaB) binding sites. NF-kappaB activation is determined, in part, by
      the intracellular redox status. The aim of this study was to determine the
      importance of the cellular glutathione status in relation to NF-kappaB activation
      and iNOS expression in hepatocytes in vivo and in vitro. For in vivo experiments,
      rats were injected with endotoxin and sacrificed 6 hours later. Glutathione was
      depleted by diethylmaleate. For in vitro experiments, cultured hepatocytes from
      untreated rats were exposed to a cytokine mixture. Glutathione levels were
      depleted by diethylmaleate and restored by N-acetylcysteine. iNOS expression was
      assessed by Western blot, reverse transcription polymerase chain reaction, nitric
      oxide (NO) metabolites, and immunohistochemistry. NF-kappaB binding was assessed
      by electrophoretic mobility shift assay. Endotoxin-induced iNOS expression in rat
      liver was prominent in hepatocytes, Kupffer cells, and inflammatory cells, in
      particular neutrophils. Glutathione depletion prevented iNOS induction in
      hepatocytes, but not in inflammatory cells. iNOS protein levels were in
      accordance with iNOS messenger RNA and NO metabolites in plasma. Glutathione
      depletion did not affect neutrophil infiltration. Cytokines strongly induced iNOS
      in cultured hepatocytes. Induction was prevented by glutathione depletion and
      could be restored by addition of N-acetylcysteine. NF-kappaB binding correlated
      with iNOS induction. In conclusion, in this study we show that iNOS induction in
      hepatocytes in vivo and in vitro is dependent on the intracellular glutathione
      status and correlates with NF-kappaB binding. Glutathione-depletion has no effect
      on the expression of iNOS in inflammatory cells, nor on neutrophil infiltration.

PMID- 9918919
TI  - Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a
      case-controlled, hemodynamic study of 17 consecutive cases.
AB  - Out of a prospective series of 142 consecutive episodes of hypoxic (ischemic)
      hepatitis (HH), we identified 17 episodes associated with an acute exacerbation
      of chronic respiratory failure (CRF) without left cardiac failure. In the aim to
      evaluate the role of arterial hypoxemia in the pathogenesis of HH associated with
      respiratory failure, these 17 episodes of HH (study group) were hemodynamically
      compared with a control group of 17 episodes of HH associated with congestive
      heart failure (CHF) (control group 1) and a group of 16 episodes of acute
      respiratory failure (ARF) not complicated by HH (control group 2). Arterial
      hypoxemia was significantly more severe in the study group (arterial blood
      tension in O2 [PaO2], 34 mm Hg) than in control group 1 (PaO2, 70 mm Hg; P
      <.0001) and control group 2 (PaO2, 45.5 mm Hg; P =.002). The role of arterial
      hypoxemia, however, appeared weakened by comparable degrees of systemic
      hypotension and liver passive congestion in episodes of HH associated with CRF
      and episodes of HH associated with CHF. Finally, the causative role of arterial
      hypoxemia emerged from hemodynamic measurements of cardiac index (CI), systemic
      vascular resistances (SVR), and oxygen transport: systemic hypotension in HH
      associated with CHF (control group 1) was the result of a fall in CI (median, 2.
      33 L/min. m2; range, 1.21-3.14 L/min. m2) associated with high SVR (median, 2,492
      dyn. s/cm5. m2; range, 1,382-4,053 dyn. s/cm5. m2), whereas in HH associated with
      respiratory failure (study group), systemic hypotension was the result of a fall
      in SVR (median, 1,053 dyn. s/cm5. m2; range, 646-3,148 dyn. s/cm5. m2), resulting
      in high CI (median, 4.23 L/min. m2; range, 1.9-5.32 L/min. m2) (P =.0087 and.
      0038 for cardiac index and SVR, respectively). Moreover, measurements of oxygen
      transport in patients with HH associated with respiratory failure showed low
      values of O2 delivery (DO2) (median, 376 mL/min. m2; range, 253-427 mL/min. m2)
      as a result of extreme arterial hypoxemia despite high CI. In conclusion, these
      hemodynamic results and additional measurements of hepatic blood flow (HBF) by
      the method of galactose clearance at a low concentration suggest that in the
      setting of HH associated with respiratory failure, the liver is not "ischemic,"
      despite hypotension, but rather "hypoxic" as a result of the combination of
      severe arterial hypoxemia and elevated central venous pressure (CVP).

PMID- 9918920
TI  - Effects of fibrillar C-terminal fragment of cleaved alpha1-antitrypsin on
      cholesterol homeostasis in HepG2 cells.
AB  - Amyloid fibrils of diverse origin are known to disturb vital cellular functions
      and induce cell death. In this study, the effects of amyloid fibrils from the C
      terminal fragment (C-36) of cleaved alpha1-antitrypsin (AAT) on low-density
      lipoprotein (LDL) metabolism were investigated in HepG2 cells. Treatment of the
      cells with C-36 fibrils (10 micromol/L) enhanced 125I-LDL binding and uptake 10
      to 15 times, and highly up-regulated levels of LDL receptor mRNA, as compared
      with control cells. Competition experiments using excess of unlabeled LDL and
      blockage experiments with a monoclonal LDL receptor antibody diminished or
      completely abolished the stimulatory effects of fibrils on LDL binding and LDL
      receptor mRNA levels, suggesting that fibrils act via the LDL receptor pathway.
      However, C-36 fibrils had no significant effect on [2-14C]acetate incorporation
      into cholesterol biosynthesis and cholesterol ester formation, but inhibited 125I
      LDL degradation by 20% and reduced bile acid biosynthesis up to 48% in a dose
      dependent manner. Preincubation of the cells with fibrils before the addition of
      LDL totally abolished the LDL inhibitory effect on unesterified cholesterol
      synthesis, further confirming the LDL receptors to be the target for C-36
      fibrils. Moreover, the expression of sterol regulatory element binding protein-1
      (SREBP-1) was found to increase twofold and more after 24 hours of incubation of
      the cells with several concentrations of C-36 fibrils. Our study suggests that
      the cytotoxicity of C-36 fibrils on HepG2 cells is associated with perturbed
      intracellular cholesterol homeostasis, induced through fibril-stimulated
      expression of the LDL receptors via the sterol-responsive element.

PMID- 9918921
TI  - Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated
      hepatic parenchymal cell injury during endotoxemia: importance of an
      intracellular oxidant stress.
AB  - Neutrophils contribute to hepatocellular injury in a number of acute inflammatory
      reactions. However, the molecular mechanism of parenchymal cell injury remains
      controversial. To address the issue of whether or not reactive oxygen species
      (ROS) are important in the injury process, we used the galactosamine/endotoxin
      (Gal/ET) model of acute liver failure, which involves a neutrophil-mediated
      parenchymal cell injury. In C3Heb/FeJ mice, Gal/ET induced a significant increase
      of hepatic and plasma levels of glutathione disulfide (GSSG), an indicator of
      oxidant stress, selectively during the neutrophil-mediated injury phase. In
      glutathione peroxidase-deficient mice (Gpx1(-/-)), Gal/ET or Gal/tumor necrosis
      factor alpha (TNF-alpha) caused more severe neutrophil-mediated liver injury
      compared with wild-type animals. However, there was no significant difference in
      other critical parameters, e.g., activation of the transcription factor, nuclear
      factor-kappaB (NF-kappaB), and soluble intercellular adhesion molecule-1 (sICAM
      1), parenchymal cell apoptosis, and neutrophil sequestration in the liver. Our
      results suggest that neutrophil-derived ROS are responsible for an intracellular
      oxidant stress in hepatocytes after Gal/ET treatment. Because of the higher
      susceptibility of Gpx1(-/-) mice to a neutrophil-mediated injury, we conclude
      that peroxides generated by neutrophils diffused into hepatocytes and contributed
      to parenchymal cell death in vivo. Thus, strengthening defense mechanisms against
      ROS in target cells can attenuate excessive inflammatory injury without affecting
      host defense reactions.

PMID- 9918922
TI  - Repeat exposure to incremental doses of acetaminophen provides protection against
      acetaminophen-induced lethality in mice: an explanation for high acetaminophen
      dosage in humans without hepatic injury.
AB  - In studies designed to simulate a clinical observation in which an individual
      became tolerant to normally lethal doses of acetaminophen (APAP), mice were
      pretreated with increasing doses of APAP for 8 days and challenged on day 9 with
      normally supralethal doses of APAP. These animals developed minimal
      hepatotoxicity after a challenge dose with a fourfold increase in LD50 to 1,350
      mg/kg. The pretreatment regimen resulted in hepatic changes including:
      centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective
      down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic
      metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione
      (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular
      proliferation. The protection against the lethal APAP doses afforded by
      pretreatment is secondary to these changes and to the associated regional shift
      in the bioactivation of the APAP challenge dose from centrilobular to periportal
      regions where CYP2E1 is not found, protective GSH is more abundant, and where
      cell-proliferative responses are better able to sustain repair. This shift in
      APAP bioactivation results in less-intense covalent binding that is more diffuse
      and spread uniformly throughout the hepatic lobe, most likely contributing to
      protection by delaying the early onset of liver injury that has been generally
      associated with centrilobular localization of the adducts. Intervention of APAP
      pretreatment-induced cell division in mice with colchicine left them resistant to
      a 500-mg/kg (normally lethal) dose of APAP, but unable to survive a 1,000-mg/kg
      APAP challenge dose. The data demonstrate multiple mechanistic components to the
      protection afforded by APAP pretreatment. Whereas metabolic and physiological
      changes not dependent on cell proliferation are adequate to protect against 500
      mg/kg APAP, these changes plus a potentiated cell-proliferative response are
      necessary for protection against the supralethal 1,000-mg/kg APAP dose.
      Furthermore, the data document an uncoupling of the traditional association
      between covalent binding and toxicity, and suggest that the assessment of
      toxicity following repeated or chronic APAP exposure must consider altered drug
      interactions and parameters besides those historically used to assess acute APAP
      overdose.

PMID- 9918923
TI  - Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells.
AB  - Nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium
      nitroprusside (SNP) modulate iron regulatory protein (IRP) activity and may,
      therefore, affect iron uptake through transferrin receptor expression. However,
      iron also enters the cell as nontransferrin-bound iron (NTBI), and the aim of
      this study was to evaluate the effects of NO donors on NTBI transport in HepG2
      cells, a model of liver physiology. Incubation with SNP and SNAP led to a time-
      and concentration-dependent reduction in Fe3+ and Fe2+ uptake, thus indicating an
      effect on the transporter rather than on the reductase. In terms of Fe2+ uptake,
      no variations in the Michaelis-Menten constant (Km) and a reduction in maximum
      uptake (Vmax) (50, 33, and 16.6 fmol/microgram protein/min in control, SNP-, and
      SNAP-treated cells, respectively) were detected, which suggested a decrease in
      the number of putative NTBI transport protein(s). Gel shift assays showed that
      IRP activity was reduced by SNP and slightly increased by SNAP. Northern blot
      analysis of transferrin receptor messenger RNA (mRNA) levels showed variations
      similar to those observed for IRPs, but both NO donors increased L-ferritin mRNA
      levels and had no effect on the stimulator of Fe transport (SFT) mRNA. In
      conclusion, NO donors significantly reduce NTBI transport in HepG2 cells, an
      effect that seems to be IRP and SFT independent. Moreover, the reduction in NTBI
      uptake after NO treatment suggests that this form of iron may play a minor role
      in the increased hepatic iron stores observed in inflammation or that other liver
      cells are more involved in this pathological condition.

PMID- 9918924
TI  - Tauroursodeoxycholate and S-adenosyl-L-methionine exert an additive ameliorating
      effect on taurolithocholate-induced cholestasis: a study in isolated rat
      hepatocyte couplets.
AB  - The monohydroxy bile acid, taurolithocholate (TLC), causes cholestasis in vivo
      and in isolated perfused livers. It is also cholestatic in vitro and, in this
      study using isolated rat hepatocyte couplets, causes a reduction of the
      accumulation of (fluorescent) bile acid in the canalicular vacuoles (cVA) of this
      polarized cell preparation. The hepatoprotective bile acid, tauroursodeoxycholate
      (TUDCA), partially protects against the action of TLC when added at the same
      time. It also partially reverses the cholestatic effect if added after the cells
      have been exposed to TLC. A second hepatoprotective compound, S-adenosyl-L
      methionine (SAMe) also not only partially protects against the action of TLC when
      added at the same time, but it too is able to partially reverse the cholestatic
      effect. Neither hepatoprotective agent is fully effective alone, but their
      effects are additive. In combination, a full restoration of cVA is observed in
      moderate cholestasis, but not in severe cholestasis. We discuss briefly some
      possible mechanisms involved in the additive mode of action of both
      hepatoprotective compounds. In summary, we show for the first time that SAMe and
      TUDCA can exert an additive effect in the amelioration of TLC-induced cholestasis
      in isolated rat hepatocyte couplets. This finding may be of possible clinical
      relevance.

PMID- 9918925
TI  - Modulation of protein kinase C by taurolithocholic acid in isolated rat
      hepatocytes.
AB  - The protein kinase C (PKC) family of isoenzymes plays a key role in the
      regulation of hepatocellular secretion. The hydrophobic and cholestatic bile
      acid, taurolithocholic acid (TLCA), acts as a potent Ca++ agonist in isolated
      hepatocytes. However, its effect on PKC isoforms has not been elucidated. Here we
      investigate the effects of TLCA at low micromolar concentrations on the
      distribution of PKC isoforms and on membrane-associated PKC activity. The
      distribution of PKC isoforms was determined in isolated rat hepatocytes in short
      term culture using Western blotting and immunofluorescence techniques. PKC
      activity was measured radiochemically. TLCA (10 micromol/L) induced selective
      translocation of epsilon-PKC by 47.9% +/- 20.5% (P <.02 vs. controls; n = 7), but
      not of alpha-, delta-, and zeta-PKC to the hepatocellular membranes, whereas the
      phorbol ester, phorbol 12-myristate 13-acetate (PMA) (1 micromol/L) caused
      translocation of all mobile isoforms, alpha-, delta-, and epsilon-PKC, as shown
      by immunoblotting. Immunofluorescence studies demonstrated selective
      translocation of epsilon-PKC to the canalicular membranes of isolated rat
      hepatocyte couplets by TLCA (10 micromol/L), but predominant translocation to
      intracellular and basolateral membranes by PMA (1 micromol/L). Both TLCA (10
      micromol/L) and PMA (1 micromol/L) stimulated membrane-bound PKC activity by
      60.5% +/- 45. 8% (P <.05 vs. controls; n = 5) and 72.4% +/- 37.2% (P <.05; n =
      5), respectively. TLCA at lower concentrations (5 micromol/L) was less effective.
      Because activation of epsilon-PKC has been associated with impairment of vesicle
      mediated targeting and insertion of membrane proteins in secretory cells, it is
      attractive to speculate that TLCA reduces bile secretory capacity of the liver
      cell by activation of epsilon-PKC at the canalicular membrane.

PMID- 9918926
TI  - Hepatic sequestration and modulation of the canalicular transport of the organic
      cation, daunorubicin, in the Rat.
AB  - In contrast to organic anions, substrates for the canalicular mdr1a and b are
      usually organic cations and are often sequestered in high concentrations in
      intracellular acidic compartments. Because many of these compounds are
      therapeutic agents, we investigated if their sequestration could be regulated. We
      used isolated perfused rat liver (IPRL), isolated rat hepatocyte couplets (IRHC),
      and WIF-B cells to study the cellular localization and biliary excretion of the
      fluorescent cation, daunorubicin (DNR). Despite rapid (within 15 minutes) and
      efficient (>90%) cellular uptake in the IPRL, only approximately 10% of the dose
      administered (0.2-20 micromol) was excreted in bile after 85 minutes. Confocal
      microscopy revealed fluorescence predominantly in vesicles in the pericanalicular
      region in IPRL, IRHC, and WIF-B cells. Treatment of these cells with chloroquine
      and bafilomycin A, agents that disrupt the pH gradient across the vesicular
      membrane, resulted in a loss of vesicular fluorescence, reversible in the case of
      bafilomycin A. Taurocholate (TC) and dibutyryl cAMP (DBcAMP), stimulators of
      transcytotic vesicular transport, increased the biliary recovery of DNR
      significantly above controls, by 70% and 35%, respectively. The microtubule
      destabilizer, nocodazole, decreased biliary excretion of DNR. No effect on
      secretion was noted in TR- mutant rats deficient in mrp2. Coadministration of
      verapamil, an inhibitor of mdr1, also decreased DNR excretion. While TC and
      DBcAMP did not affect the fluorescent intensity or pattern of distribution in
      IRHC, nocodazole resulted in redistribution of DNR to peripheral punctuate
      structures. These findings suggest that the organic cation, DNR, is largely
      sequestered in cells such as hepatocytes, yet its excretion can still be
      modulated.

PMID- 9918927
TI  - Three-dimensional reconstruction of parenchymal units in the liver of the rat.
AB  - To investigate the parenchymal units in the liver of the rat three-dimensionally,
      15 micrometer cryosections were used for the demonstration of glucose-6
      phosphatase (G6Pase) activity to visualize the borders of the individual units.
      Together with the supplying and draining vessels, they were traced through a
      sequence of 146 sections and reconstructed. A cone-shaped secondary unit with a
      height of 2.1 mm and a volume of 3.3 mm3 was reconstructed. It was "covered" by a
      continuous vascular surface, consisting of portal tracts and vascular septa,
      connecting the portal venular branches. The secondary unit was subdivided by
      portal tracts and vascular septa, and by branches of a draining central venular
      tree into 14 primary units. Most of them were tri- to heptahedral in shape. The
      height varied between 330 and 840 micrometer, and the volume varied between 0.094
      and 0.621 mm3. The branches of the portal venular tree, with diameters from 28 +/
      5 micrometer to 61 +/- 14 micrometer, were oriented preferentially along the
      vertical axis of the units. Most of the primary units were drained by single
      branches of the central venular tree, located in the center and oriented along
      the vertical axis of the units. Vessel diameters ranged from 62 +/- 14 micrometer
      to 216 +/- 9 micrometer. The average length of the sinusoids was 355 +/- 3
      micrometer. From the results of this reconstruction study, it was concluded that
      the concept of the liver acinus cannot be applied to the liver of the rat.

PMID- 9918928
TI  - Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic
      heterogeneity but genetic homogeneity.
AB  - Recurrent familial intrahepatic cholestasis is an autosomal recessive disorder
      characterized by episodes of severe pruritus and jaundice lasting for weeks to
      months without extrahepatic bile duct obstruction. Symptom-free intervals may
      last for months to years, and chronic liver damage does not develop. We recently
      studied four of the five patients from the Faeroe Islands described by us 30
      years ago (one had recently died) and an additional five patients that were
      identified after the initial report. The episodes of cholestasis were more
      frequent and severe in patients with early onset, but tended to reduce in
      frequency with age. The youngest patient, aged 25 years, who had had 16 episodes
      each lasting about 6 months, had a liver transplant after which no further
      episodes were recorded (1 year after surgery). Signs of chronic liver disease
      were absent in all patients. The FIC1 gene was investigated for mutations in the
      surviving patients. A single mutation (I661T) was found on both chromosomes in
      all nine patients, indicating that they are genetically identical for the disease
      causing defect. Nevertheless, considerable differences among patients were
      observed clinically.

PMID- 9918929
TI  - Entry and integration of transplanted hepatocytes in rat liver plates occur by
      disruption of hepatic sinusoidal endothelium.
AB  - To establish the process by which transplanted cells integrate into the liver
      parenchyma, we used dipeptidyl peptidase IV-deficient F344 rats as hosts. On
      intrasplenic injection, transplanted hepatocytes immediately entered liver
      sinusoids, along with attenuation of portal vein radicles on angiography.
      However, a large fraction of transplanted cells (>70%) was rapidly cleared from
      portal spaces by phagocyte/macrophage responses. On the other hand, transplanted
      hepatocytes entering the hepatic sinusoids showed superior survival. These cells
      translocated from sinusoids into liver plates between 16 and 20 hours after
      transplantation, during which electron microscopy showed disruption of the
      sinusoidal endothelium. Interestingly, production of vascular endothelial growth
      factor was observed in hepatocytes before endothelial disruptions. Portal
      hypertension and angiographic changes resulting from cell transplantation
      resolved promptly. Integration of transplanted hepatocytes in the liver
      parenchyma required cell membrane regenesis, with hybrid gap junctions and bile
      canaliculi forming over 3 to 7 days after cell transplantation. We propose that
      strategies to deposit cells into distal hepatic sinusoids, to disrupt sinusoidal
      endothelium for facilitating cell entry into liver plates, and to accelerate cell
      integrations into liver parenchyma will advance applications of hepatocyte
      transplantation.

PMID- 9918931
TI  - Comparative evaluation of hepatitis C virus RNA quantitation by branched DNA,
      NASBA, and monitor assays.
AB  - Several studies have shown a relationship between pretreatment hepatitis C virus
      (HCV) viral load and the response to interferon (IFN) therapy, creating a need
      for quantitative HCV-RNA assays. Here, we compared three commercial methods:
      nucleic acid sequence-based amplification NASBA (Organon), branched DNA 2.0
      (bDNA) (Chiron), and Monitor (Roche), with reverse-transcription polymerase chain
      reaction (RT-PCR) as the reference. We assessed sensitivity and reproducibility
      on a well-characterized panel of sera (EUROHEP), a Chimp Rodney plasma pool, and
      samples from IFN-treated and -untreated patients with chronic hepatitis C caused
      by different HCV genotypes. The reproducibility of the NASBA and bDNA methods was
      slightly better than that of Monitor, especially for genotypes 2 and 4. NASBA had
      the highest sensitivity (99% vs. 94% and 88% with Monitor and bDNA,
      respectively), especially for the follow-up of patients on IFN. NASBA gave the
      highest HCV-RNA concentrations, which were approximately 10-fold more than with
      the bDNA assay and 100-fold more than with the Monitor kit. The linearity, tested
      on the chimp Rodney plasma pool, was better with bDNA for high viral load than
      with NASBA and Monitor, although for low concentration of HCV RNA, bDNA was
      negative. Pretreatment viral load was lower in patients who had a sustained
      virological response to IFN, although the bDNA method was not sensitive enough to
      quantify all pretreatment samples. This study indicates that gene amplification
      methods (NASBA or Monitor) have better sensitivity than bDNA assays for
      quantification of HCV RNA in patients with chronic HCV infection, although the
      bDNA and NASBA methods are more likely to quantify all genotypes. Prospective
      studies are needed to demonstrate the usefulness of quantitative assays for the
      follow-up of patients with chronic hepatitis C.

PMID- 9918930
TI  - Class VI intermediate filament protein nestin is induced during activation of rat
      hepatic stellate cells.
AB  - Hepatic stellate cells are considered to be liver-specific pericytes that play a
      key role in liver fibrosis. Because these cells express desmin and smooth muscle
      alpha-actin, they were assumed to be of myogenic origin. This hypothesis became
      doubtful when it was reported that stellate cells also express glial fibrillary
      acidic protein and neural cell adhesion molecule. In the present study, we show
      that activated stellate cells express nestin, a class VI intermediate filament
      protein originally identified as a marker for neural stem cells. Expression of
      nestin was first studied during spontaneous activation of stellate cells in
      culture. Immunohistochemistry showed that nestin-positive stellate cells already
      appeared at day 3, and nearly all the cells became positive for nestin at day 6
      and 15. The immunoreaction was present in filaments except in dividing cells. The
      presence of messenger RNA transcript for nestin was shown by reverse
      transcription polymerase chain reaction and sequencing of amplified complementary
      DNA. We then compared the presence of nestin with that of other intermediate
      filament proteins and smooth muscle alpha-actin. Immunoblotting showed that the
      relative concentrations of nestin, desmin, and vimentin increased between day 2
      and 6 in primary culture. After the initial increase vimentin leveled off, while
      nestin and desmin showed a tendency to decrease. This pattern was quite different
      from that of glial fibrillary acidic protein, which kept declining, and smooth
      muscle alpha-actin, which increased continuously up to day 13 in culture. We then
      studied the presence of nestin in normal and CCl4-injured rat liver. In normal
      liver, minimal immunoreaction for nestin was observed within the liver
      parenchyma. During induction of fibrosis by carbon tetrachloride, nestin-positive
      stellate cells appeared at 6 weeks, which was late in comparison with the
      induction of desmin and smooth muscle alpha-actin. We conclude that nestin is
      induced in stellate cells during transition from the quiescent to the activated
      phenotype; culture activation is a stronger stimulus than in vivo activation by
      injection of CCl4. Taken together with reports on expression of glial fibrillary
      acidic protein and neural cell adhesion molecule by stellate cells, new
      experimental studies on the embryonic origin of these cells are required.

PMID- 9918932
TI  - Detection of genomic- and minus-strand of hepatitis C virus RNA in the liver of
      chronic hepatitis C patients by strand-specific semiquantitative reverse
      transcriptase polymerase chain reaction.
AB  - Studies aimed at correlating the intrahepatic hepatitis C virus (HCV)-RNA level
      and anatomo-clinical features have been difficult because of sensitivity and
      specificity shortcomings of available techniques. We titered the genomic- and
      minus-strand HCV RNAs by a strand-specific, semiquantitative, genotype
      independent reverse-transcriptase polymerase chain reaction (RT-PCR) in the liver
      tissue of 61 patients with chronic hepatitis C. Findings were correlated with the
      levels of HCV RNA in the serum, the HCV genotype, the expression of intrahepatic
      HCV antigens, the histological activity (using separate scores for the lobular
      and the portal/periportal necroinflammatory activity and for the fibrosis), and
      the response to interferon alfa (IFN-alpha) treatment. Genomic- and minus-strand
      HCV RNA were detected in 59 and 57 liver specimens, respectively. The HCV-RNA
      level in the serum correlated with the genomic-strand, but not with the minus
      strand, HCV-RNA titer in the liver. No correlations were found between either
      strand of the intrahepatic HCV RNA and the level of expression of HCV antigens in
      the liver, or with the grading/staging of the underlying liver disease. The
      response to IFN-alpha treatment could be predicted by the serum HCV-RNA level and
      genotype, but not by the intrahepatic level of genomic- or minus-strand HCV RNA.
      These results suggest that, although the detection of the minus-strand HCV RNA
      reliably identifies the presence of replicating HCV in its target organ, the
      quantitative measurement of viremia remains the clinically meaningful "golden
      standard" for assessing the level of HCV replication.

PMID- 9918933
TI  - Detection of occult low-grade b-cell non-Hodgkin's lymphoma in patients with
      chronic hepatitis C infection and mixed cryoglobulinemia.
AB  - Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and has been shown
      to be associated with the benign lymphoproliferative disorder, mixed
      cryoglobulinemia (MC). Preliminary studies suggest that there may be an
      association between chronic hepatitis C, MC, and non-Hodgkin's lymphoma (NHL).
      The aim of this study was to determine whether patients with chronic HCV and MC
      have occult bone marrow NHL. Sixteen patients with chronic HCV and clinically
      active MC underwent bone marrow biopsy and aspiration. Flow cytometry was
      performed looking for abnormal B-cell lineage. Molecular genetic studies were
      performed to identify B-cell monoclonality. Nine of 16 patients (56%) had
      abnormal marrow morphology, 7 (44%) were interpreted as suspicious for lymphoma,
      and 2 (13%) as consistent with lymphoma. Flow cytometry on 13 patients identified
      5 (39%) with increased B-cell populations. Molecular analysis on 13 patients
      identified 3 (23%) with monoclonal proliferation of the B-cell lineage. All 13
      patients tested for Epstein-Barr virus were negative by polymerase chain reaction
      (PCR). Four of 16 patients (25%) had marrow morphology and evidence of a
      monoclonal B-cell population by flow cytometry and/or molecular studies,
      consistent with B-cell NHL. These findings confirm the presence of
      lymphoproliferative disorders in patients with chronic HCV and MC. Some of these
      disorders meet the morphological and molecular criteria for the diagnosis of
      malignant lymphoma.

PMID- 9918934
TI  - An economic analysis of different strategies of immunization against hepatitis A
      virus in developed countries.
AB  - Acute hepatitis A is a major public health problem in developed countries, and
      because a large proportion of patients with acute hepatitis A do not have any
      identifiable risk factors, current practice of targeting the high-risk groups for
      vaccination against hepatitis A virus (HAV) is unlikely to have a significant
      impact on the overall incidence of acute hepatitis A. No economic analysis of
      strategies of mass immunization against HAV is available. Three different
      strategies of immunization against HAV using commercially available inactivated
      vaccine were compared in a Markov model analysis of a cohort of 2-year-old
      healthy children in a developed country. In strategy I, universal vaccination was
      pursued. In strategy II, children were initially screened for antibody and, if
      susceptible, they were vaccinated. In strategy III, no vaccination was offered.
      Cost per person and quality adjusted life-years (QALY) gained in each strategy
      were the outcome measures compared. The baseline analysis showed that strategy II
      is more cost-effective than strategy I, with marginal cost-effectiveness ratios
      of $7,267. 67 and $12,833.34, respectively, compared with a strategy of no
      intervention. Sensitivity analysis showed that if the cost of the two-dose
      vaccine could be reduced to less than $57, the strategy of universal vaccination
      would be the preferred immunization strategy. Different strategies of mass
      immunization against HAV in the developed countries are cost-effective by current
      standards of health care interventions and should be considered for incorporation
      into current childhood immunization programs.

PMID- 9918935
TI  - The hepatitis B virus-trimera mouse: a model for human HBV infection and
      evaluation of anti-HBV therapeutic agents.
AB  - Previous studies have demonstrated the feasibility of implantation of human blood
      cells or tissues in lethally irradiated mice or rats, radioprotected with SCID
      mouse bone marrow cells: The Trimera system. In the present study, we describe
      the development of a mouse Trimera model for human hepatitis B virus (HBV)
      infection. In this model, viremia is induced by transplantation of ex vivo HBV
      infected human liver fragments. Engraftment of the human liver fragments,
      evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression,
      was observed in 85% of the transplanted animals 1 month postimplantation. Viremia
      levels were determined in these mice by measuring serum HBV DNA using polymerase
      chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first
      detected 8 days after liver transplantation. Viremia attains a peak between days
      18 and 25 when HBV infection is observed in 85% of the transplanted animals. The
      HBV-Trimera model was used to evaluate the therapeutic effects of human
      polyclonal anti-HBs antibodies (Hepatect) and of two reverse-transcriptase
      inhibitors, lamivudine (3TC) and beta-L-5-fluoro-2',3'-dideoxycytidine (beta-L
      5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both
      the percentage of infected animals and the viral load in their sera. Treatment
      cessation resulted in rebound of viral load, indicating HBV replication upon drug
      withdrawal. These results show that the HBV-Trimera model represents a novel
      experimental tool for simulating human HBV infection and evaluating potential
      anti-HBV therapeutic agents.

PMID- 9918936
TI  - Acute liver injury following infection with a cytopathic strain of duck hepatitis
      B virus.
AB  - A variant avian hepadnavirus that has been shown to destroy hepatocytes in vitro
      was found to be cytopathic in vivo. A single amino acid change of glycine to
      glutamic acid at position 133 (G133E) in the preS protein of duck hepatitis B
      virus (DHBV) caused an increase in the intranuclear pool of viral covalently
      closed circular DNA (cccDNA), resulting in a transient elevation of viral
      replication and eventual hepatocyte destruction. In vivo viral infection with the
      G133E virus was compared with infection with wild-type virus over a 72-day
      period. Birds were inoculated with virus at day 2 post-hatch to ensure a high
      percentage of infected hepatocytes and potential persistence of virus. Birds
      infected with the G133E virus had increased periportal cellular proliferation and
      numerous lysed apoptotic hepatocytes following 100% infection of hepatocytes. The
      liver damage within G133E virus-infected birds subsided over time, resulting in
      mild chronic hepatitis that was similar to that observed within wild-type virus
      infected birds. The subsidence of liver damage in G133E virus-infected birds
      coincided with a reduction of viral cccDNA to wild-type virus levels in the
      liver. Our study indicates that maintenance of wild-type levels of viral cccDNA
      promotes persistence of virus infection by establishing a noncytopathic
      infection.

PMID- 9918937
TI  - Clinical and histological outcome after hepatitis B e antigen to antibody
      seroconversion in children with chronic hepatitis B.
AB  - Data regarding the outcome of children with chronic hepatitis B after
      seroconversion are scarce. We describe the long-term evolution of these patients.
      One hundred and three children with antibody against hepatitis B e antigen and
      normal alanine aminotransferase (ALT) levels were followed for 0.6 to 12.5 years
      (mean, 6.3 years). Paired liver biopsies (before and after seroconversion) were
      available in 83 cases. Final biopsies were obtained 0.5 to 12.5 years (mean, 4.5
      years) after seroconversion. ALT levels remained normal in most of the children
      (79%) throughout the follow-up. All children, except five who lost hepatitis B
      surface antigen, had serum viral DNA detected by polymerase chain reaction. When
      comparing baseline and final liver biopsies, a significant improvement (P <.001)
      was found in the histological activity index and in the necrosis, cytolysis,
      inflammation, and fibrosis scores. The histological diagnosis improvement in the
      final biopsy was significantly related (P <.001) to the time from seroconversion
      to the biopsy performance. All children had viral DNA on their final liver
      biopsy. In summary, seroconversion and ALT normalization are quite stable
      findings in children, and no differences in the long-term outcome between treated
      and untreated children were found. In light of the histological outcome, it seems
      unnecessary to perform a follow-up liver biopsy in these cases.

PMID- 9918939
TI  - Hepatitis C virus RNA profiles in chronically infected individuals: do they
      relate to disease activity?
AB  - Fluctuations of hepatitis C virus (HCV)-RNA serum levels were monitored in a
      multicenter study in 76 chronic HCV carriers who had been followed longitudinally
      without receiving antiviral therapy to assess their relation with the course of
      liver disease activity. Forty-four patients had normal transaminases over more
      than 2 years, while 32 additional patients had fluctuating levels. Viral load was
      measured in serial serum samples prospectively collected for 10 to 12 months in
      54 patients and in sera stored yearly up to 8 years in an additional 22 patients.
      In patients tested monthly, a lesser extent of fluctuations was detected in cases
      with constantly normal transaminases as compared with those with fluctuating
      transaminases. In the former group, the mean difference between maximum and
      minimum values observed in each individual patient was 0.7 Log, while in the
      latter group, it was 1.3 Log (P =.0004). Most of these patients experienced, on
      average, three peaks of viremia over 1 year. The range of variation observed upon
      yearly testing was between 0.2 and 2.2 Log and did not reach statistical
      significance between the two groups. In conclusion, a careful viral replication
      profile can be achieved only by monthly testing, because longer time intervals
      could miss viremia fluctuations. HCV-RNA levels are more stable in asymptomatic
      HCV carriers than in patients with biochemical activity of liver disease.

PMID- 9918938
TI  - Transfection of a rat hepatoma cell line with a construct expressing human liver
      annexin V confers susceptibility to hepatitis B virus infection.
AB  - Previously, we have found that human liver annexin V (hA-V; in earlier reports
      referred as Endonexin II) is a specific hepatitis B surface antigen (HBsAg)
      binding protein. In this study, we demonstrate that transfection of rat hepatoma
      FTO 2B cells, a cell line that is not infectable by hepatitis B virus (HBV) and
      does not express hA-V, with a construct containing the hA-V gene, resulted in hA
      V expressing cells susceptible to HBV infection. After in vitro infection,
      transfected FTO cells (assigned as FTO 9.1 cells) expressing hA-V in cultures
      were shown to contain HBV-precore/core, X mRNAs, and covalently closed circular
      (ccc) DNA as detected by polymerase chain reaction (PCR). The presence of HBV ccc
      and replicative intermediate DNA was also demonstrated by Southern blot
      hybridization assay. HBV DNA secreted in the culture medium was also evident as
      determined by quantitative branched DNA (bDNA) assay. HBsAg and hepatitis B core
      antigen (HBcAg) could also be detected by an immunocytochemical method in 10% to
      15% of the cells at day 3 and day 5 after infection. Infectivity of in vitro
      propagated HBV was demonstrated by infection of the naive FTO 9.1 cells with the
      culture supernatant from HBV-carrier cultures. In contrast to primary cultures of
      human hepatocytes and FTO 9.1 cells, primary rat and mouse hepatocytes, as well
      as rat hepatoma cell lines that do not express hA-V, are not susceptible to HBV
      infection. These findings suggest that hA-V plays a key role in the initial step
      of HBV infection and that the species-specific susceptibility to HBV infection
      and replication in hepatocytes is associated with the expression of hA-V.

PMID- 9918940
TI  - A prospective, community-based evaluation of liver enzymes in individuals with
      hepatitis C after drug use.
AB  - Serum alanine transaminase (ALT) levels are used to select hepatitis C virus
      (HCV)-infected patients for treatment and liver biopsy. However, the natural
      history of these measurements is poorly understood. To examine the hypothesis
      that ALT levels vary over time in HCV-infected patients, serial serum ALT levels
      were prospectively measured in a cohort of 1,235 persons with a history of prior
      illicit drug use. Over 25 months of follow-up, there was a median of four
      evaluations per patient. ALT values were higher in 1,164 (94%) HCV-infected
      individuals than in 71 (6%) HCV-uninfected individuals. The remainder of the
      analysis focused on these HCV-infected individuals, 647 (62%) of whom had normal
      ALT values at their initial visit. However, 323 (49%) of these had at least one
      elevated ALT over the next 25 months. Of the 395 patients whose ALT was initially
      abnormal, 332 (84%) had at least one normal value over the next 25 months.
      Overall, among individuals with four or more visits, ALT values were persistently
      normal in 42%, persistently elevated in 15%, and intermittently elevated in 43%.
      Because serum ALT levels have high visit-to-visit variability, single assessments
      should not be used to manage HCV-infected individuals. Further investigation is
      needed to ascertain the correlation of serial ALT trends with important disease
      outcomes.

PMID- 9918941
TI  - CCAAT/enhancer binding protein alpha (C/EBPalpha) is an important mediator of
      mouse C/EBPbeta protein isoform production.
AB  - Both CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta are
      intronless, yet can create various N-terminally truncated protein products with
      distinct DNA binding and transactivation potentials. These proteins can be
      generated via two distinct mechanisms, one translational and the other post
      translational. In the translational mechanism, there is alternative translational
      start site selection of the different AUG codons present in the single messenger
      RNA (mRNA) species via a process of leaky ribosome scanning. Additionally, a post
      translational method of isoform formation, through specific proteolytic cleavage
      of the full length protein has also been described. In this manuscript, we
      present evidence that the production of C/EBPbeta protein isoforms in the
      neonatal mouse liver is regulated by C/EBPalpha. In C/EBPalpha knockout mice, the
      predominant C/EBPbeta proteins are the larger 38- and 35-kd isoforms, whereas
      wild-type animals primarily possess the smaller 21- and 14-kd isoforms. These
      C/EBPalpha-dependent differences are liver specific, not present in lung or
      adipose tissues, and present at day 18 of development. Additionally, we show that
      induction of C/EBPalpha expression leads to an increase in the production of the
      21-kd C/EBPbeta isoform in cell culture studies. As the various C/EBPbeta protein
      isoforms have different transcriptional capabilities, it is important to
      understand the regulation of the production of these isoforms. Our observations
      suggest a novel role for the C/EBPalpha transcription factor in this process.

PMID- 9918942
TI  - Nestin in the liver--lessons from the brain.

PMID- 9918943
TI  - Diabetes mellitus and chronic hepatitis C virus infection.

PMID- 9918944
TI  - Three for the price of one knockout--a mouse model of a congenital peroxisomal
      disorder, steatohepatitis, and hepatocarcinogenesis.

PMID- 9918946
TI  - Molecules to maps: tools for visualization and interaction in support of
      computational biology.
AB  - The volume of data produced by genome projects, X-ray crystallography, NMR
      spectroscopy, and electron and confocal microscopy present the bioinformatics
      community with new challenges for analyzing, understanding, and exchanging this
      data. At the 1998 Pacific Symposium on Biocomputing, a track entitled 'Molecules
      to Maps: Tools for Visualization and Interaction in Computational Biology'
      provided tool developers and users with the opportunity to discuss advances in
      tools and techniques to assist scientists in evaluating, absorbing, navigating,
      and correlating this sea of information, through visualization and user
      interaction. In this paper we present these advances and discuss some of the
      challenges that remain to be solved.

PMID- 9918945
TI  - Profile hidden Markov models.
AB  - The recent literature on profile hidden Markov model (profile HMM) methods and
      software is reviewed. Profile HMMs turn a multiple sequence alignment into a
      position-specific scoring system suitable for searching databases for remotely
      homologous sequences. Profile HMM analyses complement standard pairwise
      comparison methods for large-scale sequence analysis. Several software
      implementations and two large libraries of profile HMMs of common protein domains
      are available. HMM methods performed comparably to threading methods in the CASP2
      structure prediction exercise.

PMID- 9918947
TI  - Weighting hidden Markov models for maximum discrimination.
AB  - MOTIVATION: Hidden Markov models can efficiently and automatically build
      statistical representations of related sequences. Unfortunately, training sets
      are frequently biased toward one subgroup of sequences, leading to an
      insufficiently general model. This work evaluates sequence weighting methods
      based on the maximum-discrimination idea. RESULTS: One good method scales
      sequence weights by an exponential that ranges between 0.1 for the best scoring
      sequence and 1.0 for the worst. Experiments with a curated data set show that
      while training with one or two sequences performed worse than single-sequence
      Probabilistic Smith-Waterman, training with five or ten sequences reduced errors
      by 20% and 51%, respectively. This new version of the SAM HMM suite outperforms
      HMMer (17% reduction over PSW for 10 training sequences), Meta-MEME (28%
      reduction), and unweighted SAM (31% reduction). AVAILABILITY: A WWW server, as
      well as information on obtaining the Sequence Alignment and Modeling (SAM)
      software suite and additional data from this work, can be found at
      http://www.cse.ucse. edu/research/compbio/sam.html

PMID- 9918948
TI  - Domain identification by clustering sequence alignments.
AB  - MOTIVATION: As sequence databases grow rapidly, results from sequence comparison
      searches using fast search methods such as BLAST and FASTA tend to be long and
      difficult to digest. RESULTS: In this paper, we present a new method to extract
      domain information from sequence comparison searches by clustering the resulting
      alignments according to their similarity to the query sequence. Efficient tree
      structures and algorithms are used to organize the alignment data such that
      structurally conserved elements can be easily identified. The hierarchical nature
      of the data structures used and the flexible X-Window-based interface provide an
      efficient and intuitive means to explore the alignment data at different levels
      so that the common domains, as well as distantly related features, can be
      explored. AVAILABILITY: The clustering program is available by anonymous ftp at:
      ftp.embl-ebi.ac.uk under directory /pub/software/unix, file: clustering.tar.Z.

PMID- 9918949
TI  - A method for comparing circular genomes from gene locations: application to
      mitochondrial genomes.
AB  - MOTIVATION: Data on the entire structures of organelle and bacterial genomes,
      most of which are known to be circular, have accumulated at a rapid pace. This
      information enables us to utilize the locations of homologous gene pairs for
      measuring the dissimilarity between complete genomic structures. RESULTS: A
      macroscopic distance is presented for comparing circular genomes from their
      overall structures, on the basis of the locations of two pairs of homologous
      genes on the compared genomes. The novel aspect of our method is that the
      comparison between the genomes automatically reveals a relationship based on the
      information on all gene locations, by incorporating the mobility of each gene,
      which includes not only the gene order, but also the relative location between
      gene pairs. The plausibility of the newly defined distances is evaluated by means
      of 44 mitochondrial genomes. The genome distance shows high performance for
      quantitatively describing the differences between the gene organizations of the
      genomes. AVAILABILITY: Since the programs implementing these calculations require
      well-arranged gene organization data, they have not been released yet. However,
      one of the authors will analyze circular genomes upon request. Data on the gene
      organizations may be submitted electronically to the address below.

PMID- 9918950
TI  - Representing metabolic pathway information: an object-oriented approach.
AB  - MOTIVATION: The University of Minnesota Biocatalysis/Biodegradation Database (UM
      BBD) is a website providing information and dynamic links for microbial metabolic
      pathways, enzyme reactions, and their substrates and products. The Compound,
      Organism, Reaction and Enzyme (CORE) object-oriented database management system
      was developed to contain and serve this information. RESULTS: CORE was developed
      using Java, an object-oriented programming language, and PSE persistent object
      classes from Object Design, Inc. CORE dynamically generates descriptive web pages
      for reactions, compounds and enzymes, and reconstructs ad hoc pathway maps
      starting from any UM-BBD reaction. AVAILABILITY: CORE code is available from the
      authors upon request. CORE is accessible through the UM-BBD at: http://www.
      labmed.umn.edu/umbbd/index.html.

PMID- 9918951
TI  - Zomit: biological data visualization and browsing.
AB  - MOTIVATION: The problems caused by the difficulty in visualizing and browsing
      biological databases have become crucial. Scientists can no longer interact
      directly with the huge amount of available data. However, future breakthroughs in
      biology depend on this interaction. We propose a new metaphor for biological data
      visualization and browsing that allows navigation in very large databases in an
      intuitive way. The concepts underlying our approach are based on navigation and
      visualization with zooming, semantic zooming and portals; and on data
      transformation via magic lenses. We think that these new visualization and
      navigation techniques should be applied globally to a federation of biological
      databases. RESULTS: We have implemented a generic tool, called Zomit, that
      provides an application programming interface for developing servers for such
      navigation and visualization, and a generic architecture-independent client
      (Javatrade mark applet) that queries such servers. As an illustration of the
      capabilities of our approach, we have developed ZoomMap, a prototype browser for
      the HuGeMap human genome map database. AVAILABILITY: Zomit and ZoomMap are
      available at the URL http://www.infobiogen.fr/services/zomit.

PMID- 9918952
TI  - VIRTLAB: a virtual molecular biology laboratory.
AB  - SUMMARY: VIRTLAB is a self-training program based on PBL (Problem-Based-Learning
      Pathway) built to simulate a molecular biology laboratory. It has been designed
      to stimulate students in the biological sciences to analyse and solve molecular
      biology problems using standard laboratory techniques (e.g. restriction enzyme
      digestions, analytical and preparative agarose gels, DNA cloning and sequencing,
      etc.) and can thus be viewed as a teaching aid. AVAILABILITY: The VIRTLAB package
      is distributed free of charge to non-profit organisations by the authors
      (virtlab@biol.dgbm. unina.it). On-line help and tutorials, available now in
      English, French, Italian, and shortly in German, are provided with the software
      or at http://biol.dgbm.unina.it:8080/virtlab.html++ +

PMID- 9918953
TI  - MODELTEST: testing the model of DNA substitution.
AB  - SUMMARY: The program MODELTEST uses log likelihood scores to establish the model
      of DNA evolution that best fits the data. AVAILABILITY: The MODELTEST package,
      including the source code and some documentation is available at
      http://bioag.byu. edu/zoology/crandall_lab/modeltest.html.

PMID- 9918954
TI  - GeneTree: comparing gene and species phylogenies using reconciled trees.
AB  - SUMMARY: GeneTree is a program for comparing gene and species trees using
      reconciled trees. The program can compute the cost of embedding a gene tree
      within a species tree, visually display the location and number of gene
      duplications and losses, and search for optimal species trees. AVAILABILITY: The
      program is free and is available at ((http://taxonomy.zoology.gla.ac.
      uk/rod/genetree/genetree.html)).

PMID- 9918955
TI  - JavaShade: multiple sequence alignment box-and-shading on the World Wide Web.
AB  - RESULTS: JavaShade is a multiple sequence alignment box-and-shade tool for
      generating high quality printed output that uses a variety of methods for boxing
      and shading, allowing the most appropriate functions to be chosen for displaying
      the most meaningful positions in an alignment. AVAILABILITY: JavaShade is
      available from the WWW at http://industry.ebi.ac.uk/JavaShade

PMID- 9918956
TI  - SPEM: a parser for EMBL style flat file database entries.
AB  - SUMMARY: We present a set of Perl modules for the flexible and robust parsing and
      editing of EMBL/SWISS-PROT databases. AVAILABILITY: The Web page at
      http://www.sanger.ac. uk/Software/PerlModule/ provides information about
      downloading the SPEM and PrEMBL modules, and provides links to documentation and
      example code.

PMID- 9918957
TI  - WEBMAP: radiation hybrid mapping on the WWW.
AB  - SUMMARY: A Java interface to radiation hybrid (RH) mapping software is described
      which enables users to build and interactively refine RH maps over the web.
      AVAILABILITY: The Java applets described here are available on the internet at
      http://www.oxmol.com/biolib/webmap/.

PMID- 9918958
TI  - An Internet linkage and mutation database for the complex phenotype asthma.
AB  - SUMMARY: The paper presents details of database construction, website
      installation and server architecture of the asthma and allergy gene database.
      AVAILABILITY: Database and server templates are available on request from the
      first author. SUPPLEMENTARY INFORMATION: The URL of the asthma and allergy gene
      database is http://cooke.gsf.de

PMID- 9918959
TI  - And justice for whom?

PMID- 9918960
TI  - Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel
      node technique.
AB  - BACKGROUND: The purpose of the study was to determine the accuracy and role of
      the sentinel node technique in patients with non-small cell lung cancer. METHODS:
      This study was carried out on 36 consecutive patients undergoing lung resection.
      Peritumoral tissue was infiltrated with isosulfan blue dye and the first lymph
      node to stain was identified as a sentinel node. Sensitivity and specificity of
      the sentinel node in predicting the status of other lymph node stations were
      determined. RESULTS: Seventeen patients had sentinel lymph nodes. In 9 of these
      17 cases neither the sentinel node nor any other lymph node contained metastatic
      carcinoma. In 5 cases the sentinel node was in the mediastinum and documented
      unexpected N2 disease. In 19 patients no sentinel node was found. Final lymph
      node statuses were N0 in 13 patients, N1 in 5, and N2 in 1. CONCLUSIONS: The use
      of isosulfan blue for intraoperative lymphatic mapping is feasible. The
      specificity in our experience was good; 9 of 9 patients with negative sentinel
      nodes were found to be N0 on the final pathology report. Unexpected N2 disease
      was found in 5 patients. The accumulation of further experience will determine
      the role of the sentinel node technique in patients with non-small cell lung
      cancer.

PMID- 9918961
TI  - Induction chemotherapy for T4 centrally located non-small cell lung cancer.
AB  - OBJECTIVE: We used induction chemotherapy in a prospective, single-institution
      clinical trial intended to achieve resectability in patients with centrally
      located, unresectable T4 non-small cell lung cancer. Other types of IIIB disease
      were excluded. METHODS: Between January 1990 and April 1996, we enrolled 57
      patients with histologically confirmed non-small cell lung cancer. Eligibility
      criteria for T4 were clinical (superior vena cava syndrome, 9 patients), vocal
      cord paralysis (6 patients), dysphagia from esophageal involvement (1 patient),
      radiologic (computed tomography and magnetic resonance evidence of infiltration,
      10 patients), bronchoscopic (tracheal infiltration, 11 patients), and
      thoracoscopic (histologically proven mediastinal infiltration, 20 patients).
      After 3 cycles of cisplatin (120 mg/m2), vinblastine (4 mg/m2), and mitomycin (2
      mg/m2), patients were reevaluated. RESULTS: Forty-two patients (73%; 36 men, 6
      women; age range, 42-75 years; mean, 58 years) responded to therapy and underwent
      thoracotomy; 11 patients did not respond, and 4 patients had major toxicity.
      Thirty-six patients (63% of the entire group) had complete resection. We
      performed 4 exploratory thoracotomies, 6 pneumonectomies, 32 lobectomies (20
      procedures were associated with reconstruction of hilar-mediastinal structures).
      Overall, 4 patients had no histologic evidence of disease. We had 2
      bronchopleural fistulas with 1 death and 5 other major complications. Overall
      survival at 1 and 4 years is 61.4% and 19.5%, respectively. Forty-two patients
      (73%) underwent exploratory operation, with a 4-year survival of 25.9%; 36
      patients (63%) had complete resection, with a 4-year survival of 30.5%.
      CONCLUSIONS: Induction chemotherapy is effective for downstaging and surgical
      reconversion of centrally located T4 non-small cell lung cancer. Survival is
      promising, especially in patients whose disease becomes resectable.

PMID- 9918962
TI  - Video-assisted thoracoscopy in the treatment of pleural empyema: stage-based
      management and outcome.
AB  - OBJECTIVE: Despite modern diagnostic methods and appropriate treatment, pleural
      empyema remains a serious problem. Our purpose was to assess the feasibility and
      efficacy of the video-assisted thoracoscopic surgery in the management of
      nontuberculous fibrinopurulent pleural empyema after chest tube drainage
      treatment had failed to achieve the proper results. METHODS: We present a
      prospective selected single institution series including 45 patients with pleural
      empyema who underwent an operation between March 1993 and December 1996. Mean
      preoperative length of conservative management was 37 days (range, 8-82 days).
      All patients were assessed by chest computed tomography and ultrasonography and
      underwent video-assisted thoracoscopic debridement of the empyema and
      postoperative irrigation of the pleural cavity. RESULTS: In 37 patients (82%),
      video-assisted thoracoscopic debridement was successful. In 8 cases,
      decortication by standard thoracotomy was necessary. There were no complications
      during video-assisted thoracic operations. The mean duration of chest tube
      drainage was 7. 1 days (range, 4-140 days). At follow-up (n = 35) with pulmonary
      function tests, 86% of the patients treated by video-assisted thoracic operation
      showed normal values; 14% had a moderate obstruction and restriction without
      impairment of exercise capacity, and no relapse of empyema was observed.
      CONCLUSIONS: Video-assisted thoracoscopic debridement represents a suitable
      treatment for fibrinopurulent empyema when chest tube drainage and fibrinolytics
      have failed to achieve the proper results. In an early organizing phase,
      indication for video-assisted thoracic operation should be considered in due time
      to ensure a definitive therapy with a minimally invasive intervention. For
      pleural empyema in a later organizing phase, full thoracotomy with decortication
      remains the treatment of choice.

PMID- 9918963
TI  - Indications for three-field dissection followed by esophagectomy for advanced
      carcinoma of the thoracic esophagus.
AB  - OBJECTIVE: The aim of this study was to evaluate the indication for 3-field
      lymphadenectomy (3-field dissection) followed by esophagectomy for locally
      advanced carcinoma of the thoracic esophagus in the presence of lymph node
      metastasis. METHODS: From January 1983 to December 1995, 86 patients with
      thoracic esophageal carcinoma invading muscularis propria or adventitia underwent
      radical subtotal esophagectomy after preoperative chemotherapy. Forty-six of the
      86 patients underwent a 2-field dissection (mediastinal and abdominal nodes,
      group A), and 40 patients underwent a 3-field dissection (bilateral cervical,
      mediastinal, and abdominal nodes, group B). Survival curves were compared between
      the 2 groups after stratification according to the degree of lymph node
      involvement (number of positive nodes and involvement of intrathoracic or
      intrathoracic recurrent nerve chain nodes). Potential prognostic factors of these
      86 patients were evaluated by means of Cox regression analysis. RESULTS: There
      were no significant differences in age, sex ratio, depth of tumor invasion, pTNM
      classification, or number of positive nodes between the 2 groups. Among patients
      with positive intrathoracic nodes, the 5-year survival of group B (42%) was
      significantly longer than that of group A (13%, generalized Wilcoxon test P
      =.02). Among patients with 1 to 4 positive nodes, the 5-year survival of group B
      (54%) was significantly higher than that of group A (22%, P =.01). Multivariate
      analysis revealed the number of positive nodes, age, and pT4 stage to be
      significant predictors of survival in patients with thoracic esophageal
      carcinoma. CONCLUSIONS: Three-field dissection for advanced carcinoma of the
      thoracic esophagus is effective in patients with 1 to 4 positive nodes.

PMID- 9918964
TI  - Systematic nodal dissection in the intrathoracic staging of patients with non
      small cell lung cancer.
AB  - OBJECTIVE: Although systematic nodal dissection is accepted as an important
      component of the intrathoracic staging of disease in patients undergoing
      thoracotomy for lung cancer, many surgeons still do not routinely perform it. We
      reviewed our practice to assess the information provided by its routine
      application even when lymph node metastases are considered unlikely. METHODS: The
      records of 240 patients undergoing thoracotomy for clinically staged cT1-3 N0-1
      non-small cell lung cancer were reviewed. In 5 cases (2%) mediastinal dissection
      was not performed because of specific contraindications and in 8 cases (3%)
      exploratory thoracotomy was performed. The pathologic findings in the 227
      patients who underwent pulmonary resection with systematic nodal dissection were
      analyzed. RESULTS: The median number of nodal stations, including N1 and N2,
      examined and submitted separately for histologic assessment was 7 per patient
      (range 3-13). N2 disease was disclosed in 46 patients overall (20%), including 41
      of the 227 patients undergoing pulmonary resection (18%) and 5 of those
      undergoing exploratory thoracotomy (62.5%). No subgroup had a 0% incidence of N2
      metastases. Multivariate analysis showed that younger age, increasing tumor size,
      left lower lobe origin, and bronchial origin were significant independent
      variables for prediction of lymph node metastases at the N1 level, the N2 level,
      or both. CONCLUSIONS: Because no clinical or pathologic subset of patients with a
      negligible incidence of N2 disease could be discriminated, systematic nodal
      dissection must be routinely employed for accurate intrathoracic staging of non
      small cell lung cancer.

PMID- 9918965
TI  - Dissection of the ascending aorta after previous cardiac surgery: differences in
      presentation and management.
AB  - OBJECTIVE: This study was undertaken to determine the impact of previous cardiac
      surgery on the presentation, management, and outcome of late dissection of the
      ascending aorta. PATIENTS AND METHODS: From 1976 to 1998, type A dissection
      developed in 56 patients with a history of previous cardiac surgery. Interval
      from first operation to type A dissection was 49 +/- 47 months (0.3-180 months).
      Previous operations were coronary artery bypass grafting (n = 40), aortic valve
      replacement (n = 8), and other (n = 8). RESULTS: Type A dissection was acute in
      34 patients and chronic in 22. In acute dissection, aortic insufficiency occurred
      in 50%, malperfusion in 12%, and rupture in 18%; 2 patients (6%) were in
      hemodynamically unstable condition because of rupture. Of patients with previous
      coronary bypass grafting, 98% had preoperative coronary angiography. Type A
      dissection was treated by supracoronary tube graft (84%), Bentall procedure
      (14%), or local repair (2%). Strategies for managing previous coronary bypass
      grafting included reimplantation of proximal anastomoses with a button of native
      aorta (29 patients), interposition graft to pre-existing saphenous vein grafts (9
      patients), and new saphenous vein grafts (20 patients). Eight hospital deaths
      occurred (14%). CONCLUSIONS: We conclude that (1) patients having type A
      dissection late after cardiac surgery infrequently have cardiac tamponade and
      hemodynamic collapse; (2) patients with previous coronary bypass grafting require
      coronary angiography, because operative management must account for pre-existing
      coronary artery disease; and (3) operative mortality is low, and this may be
      attributable to preoperative hemodynamic stability, delineation of coronary
      anatomy in those with previous coronary bypass grafting, and operative treatment
      of coronary artery disease.

PMID- 9918966
TI  - Noninvasive evaluation of hand circulation before radial artery harvest for
      coronary artery bypass grafting.
AB  - OBJECTIVE: Radial artery harvesting for coronary artery bypass may lead to digit
      ischemia if collateral hand circulation is inadequate. The modified Allen's test
      is the most common preoperative screening test used. Unfortunately, this test has
      high false-positive and false-negative rates. The purpose of this study was to
      compare the results of a modified Allen's test with digit pressure change during
      radial artery compression for assessing collateral circulation before radial
      artery harvest. METHODS: One hundred twenty-nine consecutive patients were
      studied before coronary artery bypass operations. A modified Allen's test was
      performed with Doppler ultrasound to assess blood flow in the superficial palmar
      arch before and during radial artery compression. A decreased audible Doppler
      signal after radial artery compression was considered a positive modified Allen's
      test. First and second digit pressures were measured before and during radial
      artery compression. A decrease in digit pressure of 40 mm Hg or more (digit
      DeltaP) with radial artery compression was considered positive. RESULTS: Seven of
      14 dominant extremities (50%) and 8 of the 16 nondominant extremities (50%) with
      a positive modified Allen's test had a digit DeltaP of less than 40 mm Hg (false
      positive). Sixteen of 115 dominant extremities (14%) and 5 of 112 nondominant
      extremities (4%) with a negative Allen's test had a digit DeltaP of 40 mm Hg or
      more with radial artery compression (false negative). CONCLUSION: Use of the
      modified Allen's test for screening before radial artery harvest may
      unnecessarily exclude some patients from use of this conduit and may also place a
      number of patients at risk for digit ischemia from such harvest. Direct digit
      pressure measurement is a simple, objective method that may more precisely select
      patients for radial artery harvest. Additional studies are needed to define
      objective digital pressure criteria that will accurately predict patients at risk
      for hand ischemia after radial harvest.

PMID- 9918967
TI  - Multicenter study of stentless valve replacement in the small aortic root.
AB  - OBJECTIVE: A clinical study was conducted to evaluate the results of stentless
      porcine valves in patients with a small aortic root (19- and 21-mm aortic
      anulus). METHODS: Of 567 patients, from 4 surgical institutions, 171 patients
      (30.1%) had a small aortic root, comprising 163 cases with calcified aortic
      stenosis and 8 cases with predominant valvular insufficiency. Sixty patients had
      associated mitral or coronary lesions. Mean age was 72 +/- 4.2 years. Forty-seven
      patients with a small aortic root had a 19-mm anulus, and 124 patients had a 21
      mm anulus. The body surface area was, respectively, 1.55 +/- 0.2 m2 and 1.78 +/-
      0.45 m2. Hemodynamic evaluation of the stentless valve comprised serial measures
      of mean gradients, effective orifice area, and left ventricular mass reduction.
      Complication rates for secondary events were evaluated over a 6-year period.
      RESULTS: The hospital mortality rate was 3.5%. The mean gradients after the first
      year were 9 +/- 2 mm Hg and 6 +/- 1.7 mm Hg in patients with a 19-mm and a 21-mm
      anulus, respectively. Effective orifice area was 1.45 +/- 0.3 cm2 and 1.72 +/-
      0.4 cm2. Gradients and surfaces remained stable throughout the study period.
      Aortic regurgitation was zero to trace. Left ventricular mass at discharge and at
      1 year were, respectively, 296 +/- 127 g and 215 +/- 102 g for patients with a 19
      mm anulus and 281 +/- 75 g and 236 +/- 15 g for patients with a 21-mm anulus.
      CONCLUSIONS: Stentless valves are a suitable device for elderly patients with
      small aortic roots, which leave only mild residual obstruction.

PMID- 9918968
TI  - The impact of age, coronary artery disease, and cardiac comorbidity on late
      survival after bioprosthetic aortic valve replacement.
AB  - OBJECTIVES: This study was designed to determine the effects of age, coronary
      artery disease and other cardiac comorbidities on late outcome following
      bioprosthetic aortic valve replacement. METHODS: Data were prospectively
      collected on 670 patients undergoing aortic valve replacement with the Hancock II
      bioprosthesis (Medtronic, Inc, Minneapolis, Minn) between 1982 and 1994. Mean
      patient age was 65 +/- 12 years (median, 68 years; range, 18-86 years). Follow-up
      was 99.7% complete at 69 +/- 40 months (median, 66 months; range, 0. 1-168
      months). Survival and freedom from reoperation were evaluated univariately by
      Kaplan-Meier analysis and multivariably by Cox regression. RESULTS: After
      adjustment for gender, Cox regression analysis revealed that age of 65 years or
      older, left ventricular dysfunction, the presence of coronary artery disease, and
      advanced New York Heart Association functional classification were associated
      with a higher risk of late death. At 12 years, survival was significantly
      different by Kaplan-Meier analysis for both age younger than 65 years (71% +/-
      4%) versus age 65 years or older (36% +/- 7%; P <.0001), left ventricular
      function grades 3 and 4 (26% +/- 13%) versus grades 1 and 2 (59% +/- 4%; P
      <.0001), no coronary artery disease (65% +/- 4%) versus coronary artery disease
      (35% +/- 8%; P <.0001), and functional class IV (33% +/- 9%) versus classes I to
      III (62% +/- 4%; P <.0001). Only 9 patients experienced primary tissue failure,
      all of whom were younger than 65 years of age. At 12 years, the freedom from
      primary tissue failure was 84% +/- 4% for those patients younger than 65 years of
      age, and 100% for those 65 years of age or older (P =.006). CONCLUSIONS: Long
      term survival after aortic valve replacement is highly dependent on age, coronary
      artery disease, functional class, and left ventricular function, although
      bioprosthetic durability is dependent almost solely on age. Due to increased
      valve durability in patients who are 65 years of age or older, the Hancock II
      bioprosthesis may be an ideal aortic valve substitute in this age group. In
      patients who are younger than 65 years of age with advanced functional class,
      impaired left ventricular function, and coronary artery disease, this valve may
      also be used with a low probability of primary tissue failure. Patients without
      additional cardiac comorbidity may outlive their bioprosthetic valve, leading to
      reoperation.

PMID- 9918969
TI  - Memantine for prevention of spinal cord injury in a rabbit model.
AB  - BACKGROUND: This study was conducted to investigate the effect of memantine, a
      noncompetitive N-methyl-d-aspartate receptor antagonist, on the neurologic
      outcome of spinal cord ischemia after aortic occlusion. MATERIALS AND METHODS:
      New Zealand White rabbits were anesthetized and spinal cord ischemia was induced
      for 40 minutes by infrarenal aortic occlusion. Animals were randomly allocated to
      3 groups. Group 1 (n = 8, control) received no pharmacologic intervention, group
      2 (n = 8) received intra-aortic memantine infusion (20 mg/kg) after aortic
      crossclamping, and group 3 (n = 8) was treated with systemic memantine infusion
      (20 mg/kg) 45 minutes before aortic occlusion. Neurologic status was scored by
      the Tarlov system (in which 4 is normal and 0 is paraplegia) at 12, 24, 36, and
      48 hours after the operation. Lumbar spinal root stimulation potentials and motor
      evoked potentials from lower limb muscles were monitored before, during, and
      after the operation. After the animals were killed, the spinal cords were studied
      histopathologically. RESULTS: All potentials disappeared shortly after aortic
      crossclamping. They returned earlier in both memantine-treated groups than in the
      placebo group. Histologic examination of spinal cords revealed a few abnormal
      motor neurons in memantine-treated rabbits but found extensive injury in the
      control group. At 12 hours the median Tarlov scores were 0 in the control group
      (group 1), 2 in the intra-aortic memantine group (group 2, P =.001 versus
      control), and 3 in the systemic group (group 3, P =.0002 versus control). At 24
      hours median Tarlov scores were 0, 2.5 (P =.0002), and 4 (P =. 0002),
      respectively. Finally, at both 36 and 48 hours median Tarlov scores were 0, 3 (P
      =.0006), and 4 (P =.0002), respectively. CONCLUSION: Memantine significantly
      reduced neurologic injury related to spinal cord ischemia and reperfusion after
      aortic occlusion.

PMID- 9918970
TI  - Quantitative angiographic assessment of coronary anastomoses performed without
      cardiopulmonary bypass.
AB  - BACKGROUND: The quality of the anastomosis performed during coronary artery
      bypass grafting without cardiopulmonary bypass is a current concern, and
      myocardial wall restraining devices have been designed to optimize results. A
      quantitative angiographic analysis was performed to assess coronary anastomoses
      performed on beating hearts. METHODS: We studied 34 patients who underwent
      coronary artery bypass grafting without cardiopulmonary bypass between February
      1996 and April 1997. The left internal thoracic artery was anastomosed to the
      left anterior descending coronary artery in all patients. Coronary angiograms
      were performed 4 +/- 2 days after the operation. The diameter of the anastomoses
      was quantified by computer-assisted analysis of grafts and native coronary
      arteries at the toe and heel of the anastomosis. RESULTS: Five of the patients
      who underwent coronary artery bypass without a stabilizer (n = 20) had stenoses
      of the internal thoracic artery grafted to the left anterior descending coronary
      artery of more than 50% at the level of the anastomosis proper, 3 had stenoses at
      the heel of the coronary anastomosis, and 5 had stenoses at the toe. One of the
      patients in whom a stabilizer was used (n = 14) had a stenosis of more than 50%
      at the anastomosis, and 1 had stenosis at the heel. Eight patients in whom the
      anastomoses were performed without stabilization (8/20, 40%) had stenoses of more
      than 50%, whereas there was only 1 stenosis of more than 50% of coronary luminal
      diameter among the patients in whom the operation was performed with a stabilizer
      (P =.02). CONCLUSION: The quantitative angiographic evaluation suggests that left
      internal thoracic artery graft to left anterior descending coronary artery
      anastomoses have a lesser degree of intraluminal stenosis when performed with the
      use of a myocardial wall stabilizer.

PMID- 9918971
TI  - Atrial fibrillation after minimally invasive coronary artery bypass grafting: A
      retrospective, matched study.
AB  - BACKGROUND: Atrial fibrillation after cardiac operations is a source of morbidity
      and resource consumption. Various factors common to cardiac operations have been
      cited as causal. Comparison of the incidences of atrial fibrillation after
      conventional cardiac operations and minimally invasive cardiac operations may
      provide some insight into the mechanisms of this complication. METHODS: All
      patients undergoing minimally invasive direct coronary artery bypass grafting
      from January 26, 1996, through September 17, 1997, were evaluated for the
      occurrence of in-hospital postoperative atrial fibrillation. Data from these 55
      patients were compared with data from a control cohort of patients undergoing
      conventional, solitary coronary artery bypass grafting. Each patient undergoing
      minimally invasive direct coronary artery bypass grafting was matched by age (+/-
      3 years) and date of operation (+/- 7 days) with a patient undergoing
      conventional coronary artery bypass grafting. RESULTS: During the period since
      the advent of minimally invasive direct coronary artery bypass grafting at our
      institution, the incidence of postoperative atrial fibrillation has been slightly
      lower among the patients undergoing this form of coronary artery bypass grafting
      (26%) than among the total population of patients undergoing conventional
      coronary artery bypass grafting (34%). Comparison of the age-matched groups,
      however, showed the incidence to be slightly but not significantly greater in the
      minimally invasive direct coronary artery bypass grafting cohort (13/55, 24%)
      than in the conventional coronary artery bypass grafting cohort (11/55, 20%; P =.
      6). The minimally invasive direct coronary artery bypass grafting group was less
      likely to be discharged with antiarrhythmic therapy than was the conventional
      coronary artery bypass grafting group (6 versus 10; P =.006). CONCLUSIONS:
      According to these data, mechanisms traditionally implicated in atrial
      fibrillation after coronary artery bypass grafting, such as the use of
      cardiopulmonary bypass, mechanical manipulation of the atrium, and atrial
      ischemia, are not causal but may be related to the duration of the arrhythmic
      complication. Strategies directed toward management and reduction of the
      incidence of postoperative atrial fibrillation should be focused accordingly.

PMID- 9918972
TI  - Mitral annular size and shape in sheep with annuloplasty rings.
AB  - BACKGROUND: Mitral annuloplasty is an important element of most mitral repairs,
      yet the effects of various types of annuloplasty rings on mitral annular dynamics
      are still debated. Recent studies suggest that flexible rings preserve
      physiologic mitral annular area change during the cardiac cycle, while rigid
      rings do not. METHODS: To clarify the effects of mitral ring annuloplasty on
      mitral annular dynamic geometry, we sutured 8 radiopaque markers equidistantly
      around the mitral anulus in 3 groups of sheep (n = 7 each: no ring, Carpentier
      Edwards semi-rigid Physio-Ring [Baxter Healthcare Corp, Edwards Division, Santa
      Ana, Calif], and Duran flexible ring [Medtronic, Inc, Minneapolis, Minn]). Ring
      sizes were selected according to anterior leaflet area and inter-trigonal
      distance (Physio-Ring 28 mm, n = 7; Duran ring 31 mm, n = 5, and 29 mm, n = 2).
      After 8 +/- 1 days of recovery, the sheep were sedated and studied by means of
      biplane videofluoroscopy. Mitral annular area was calculated from 3-dimensional
      marker coordinates without assuming circular or planar geometry. RESULTS: In the
      no ring group, mitral annular area varied during the cardiac cycle by 11% +/- 2%
      (mean +/- SEM; maximum = 7.6 +/- 0.2, minimum = 6.8 +/- 0.2 cm2; P </=.001).
      Mitral annular area was fixed in the Physio-Ring group (4. 6 +/- 0.1 cm2) and,
      surprisingly, also static in the Duran ring group (4.8 +/- 0.1 cm2; P =.26 vs
      Physio-Ring). Furthermore, mitral annular 3-dimensional shape changed in the no
      ring group during the cardiac cycle, but not in the Physio-Ring or Duran groups.
      CONCLUSIONS: Mitral annular area and shape did not change during the cardiac
      cycle after ring annuloplasty, regardless of ring type. Thus mitral annular area
      reduction, independent of intrinsic ring flexibility, is the chief mechanism
      responsible for the salutary effects of mitral ring annuloplasty.

PMID- 9918973
TI  - Robotic computer-assisted telemanipulation enhances coronary artery bypass.
AB  - OBJECTIVES: Totally endoscopic coronary artery bypass grafting depends greatly on
      perfecting the anastomosis. We tested a new computer-assisted telemanipulation
      robot (Intuitive Surgical Inc, Mountain View, Calif) in performing endoscopic
      coronary bypass. METHODS: On-bench anastomoses of the porcine arterial graft to
      the left anterior descending coronary artery were performed with both direct
      visualization and conventional surgical instruments (group I), endoscopic 3
      dimensional visualization and current endoscopic surgical instruments (group II),
      direct visualization and endoscopic instruments (group III), 3-dimensional
      endoscopic visualization and conventional surgical instruments (group IV), and
      telemanipulation robotic with 3-dimensional endoscopic visualization (group V).
      Anastomoses (n = 6 in each group) were assessed for time (minutes), quality (good
      = 3, fair = 2, poor = 1), technical difficulty (easy-difficult: 1-4), and patency
      (100% = 1, >50% = 2, <50% = 3). RESULTS: Anastomotic time was significantly
      longer in groups II and III than in groups IV and V (P </=.02). Patency was
      comparable in all groups. CONCLUSION: Telemanipulation technology may enhance the
      performance of totally endoscopic coronary artery anastomosis. The facility and
      time of an Intuitive telemanipulation anastomosis is comparable with that of a
      conventional anastomosis created under direct vision.

PMID- 9918974
TI  - Endothelin receptor blockade prevents the rise in pulmonary vascular resistance
      after cardiopulmonary bypass in lambs with increased pulmonary blood flow.
AB  - BACKGROUND: Children with increased pulmonary blood flow may experience morbidity
      as the result of increased pulmonary vascular resistance after operations in
      which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent
      vasoactive substance implicated in pulmonary hypertension, are increased after
      cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood
      flow after in utero placement of an aortopulmonary shunt, we characterized the
      changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary
      bypass and investigated the role of endothelin-1 and endothelin-A receptor
      activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old
      lambs, the shunt was closed, and vascular pressures and blood flows were
      monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707;
      1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before
      cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic
      variables were monitored, and plasma endothelin-1 concentrations were determined
      before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90
      minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure
      and pulmonary vascular resistance increased significantly in saline-treated lambs
      during the 6-hour study period (P <.05). In lambs pretreated with PD 156707,
      pulmonary arterial pressure and pulmonary vascular resistance decreased (P <.
      05). After bypass, plasma endothelin-1 concentrations increased in all lambs;
      there was a positive correlation between postbypass pulmonary vascular resistance
      and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests
      that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part,
      the rise in pulmonary vascular resistance after cardiopulmonary bypass.
      Endothelin-A receptor antagonists may decrease morbidity in children at risk for
      postbypass pulmonary hypertension. This potential therapy warrants further
      investigation.

PMID- 9918975
TI  - Excellent long-term functional outcome after an operation for anomalous left
      coronary artery from the pulmonary artery.
AB  - OBJECTIVE: The aim of this study was to review the results of operations for
      anomalous left coronary artery from the pulmonary artery and the late outcome for
      exercise capacity, left ventricular function, and mitral regurgitation. METHODS:
      Twenty-one patients underwent operations over an 18-year period (median age, 9
      months; range, 6 weeks-26 years) with a median follow-up of 6.5 years (range, 2
      months-18 years). In addition to clinical and echocardiographic follow-up,
      patients at our institution were also investigated with radionuclide scans (n =
      10) and treadmill exercise testing (n = 8). RESULTS: There were no operative or
      late deaths (0%; 95% confidence interval [CI], 0% and 16%). Five patients
      required support with a left ventricular assist device. Eighteen patients are
      currently in New York Heart Association class I, and 3 patients are mildly
      symptomatic. On nuclear gated scan at a mean of 6 years after the operation, the
      left ventricular ejection fraction was 64% (SD, 3%) at rest and increased to 74%
      (SD = 3%) on exercise (95% CI for the difference, 6%, 14%; P =.001). Treadmill
      endurance was normal for age (9.8-14.5 minutes) in those old enough to exercise.
      On echocardiography (n = 18), the current fractional shortening was 34% (SD, 4%)
      in the 15 patients with normal or only mildly abnormal ventricular septal motion.
      Three patients have undergone mitral valve operations. The left ventricular end
      diastolic dimension fell from 48 mm (SD, 5.8 mm) before surgery to 35.1 mm (SD,
      5.2 mm) at 1 year after the operation, and the fractional shortening increased
      over the first year from 19.6% (SD, 9.3%) to 32.8% (SD, 5.9%; both P <.001).
      CONCLUSIONS: Long-term clinical outcome and left ventricular function are good,
      despite severe left ventricular dysfunction at presentation.

PMID- 9918976
TI  - Role of the endothelium in placental dysfunction after fetal cardiac bypass.
AB  - BACKGROUND: Fetal cardiac bypass causes placental dysfunction, characterized by
      increased placental vascular resistance, decreased placental blood flow, hypoxia,
      and acidosis. Vasoactive factors produced by the vascular endothelium, such as
      nitric oxide and endothelin 1, are important regulators of placental vascular
      tone and may contribute to this placental dysfunction. METHODS: To investigate
      the role of the vascular endothelium in placental dysfunction related to fetal
      cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we
      determined placental hemodynamic responses before and after bypass to an
      endothelium-dependent vasodilator (acetylcholine), an endothelium-independent
      vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a
      nonspecific endothelin receptor blocker (PD 145065) was administered and
      placental hemodynamic values were measured before and after bypass. In the third
      group (n = 5) endothelin 1 levels were measured before and after bypass. RESULTS:
      Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow
      by 9% and increased placental resistance by 9%. After bypass endothelin 1
      decreased placental flow by 47% and increased resistance by 106%. There was also
      a significant attenuation of the placental vascular relaxation response to
      acetylcholine after bypass, whereas the response to nitroprusside was not
      significantly altered. In fetuses that received the PD 145065, placental vascular
      resistance increased significantly less than in control fetuses (28% versus 62%).
      Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1
      to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD
      145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased
      significantly in fetuses exposed to fetal bypass but did not change in control
      fetuses. CONCLUSIONS: The basal endothelial regulatory mechanisms of placental
      vascular tone were deranged after fetal cardiac bypass. Endothelin receptor
      blockade, which substantially reduced postbypass placental dysfunction, and other
      interventions aimed at preserving endothelial function may be effective means of
      optimizing fetal outcome after cardiac bypass.

PMID- 9918977
TI  - Surgical angioplasty of the main coronary arteries in children.
AB  - OBJECTIVE: To determine the safety and efficacy of surgical angioplasty of the
      coronary arteries in children. METHODS: We performed 9 surgical reconstructions
      of the left main coronary artery and 1 of the right coronary artery ostium in 10
      children (mean age 5.7 years; range 2 months-15 years). The basic diseases
      included the following: congenital atresia of the left coronary artery (n = 2)
      and atresia of the right coronary artery in a patient with an aortoventricular
      tunnel (n = 1); stenosis of the left main coronary artery (1) in a patient with
      Williams syndrome (n = 1), (2) in a patient with familial hypercholesterolemia (n
      = 1), (3) after the arterial switch operation for transposition of the great
      arteries (n = 3), (4) after reimplantation of an anomalous left main coronary
      artery from the pulmonary artery (n = 1), and (5) by compression after a
      reparation a l'etage ventriculaire procedure (n = 1). Myocardial viability was
      assessed by single photon emission computed tomography (thallium 201; 7/10). The
      coronary artery stem was enlarged with a saphenous (n = 5), a pericardial (n =
      4), or a polytetrafluoroethylene patch (n = 1). RESULTS: There was 1 hospital
      death and 9 patients are alive (mean follow-up 46 +/- 30 months; range 12 months
      to 10.5 years). Eight of 9 survivors had a selective coronary artery angiogram
      and had normal coronary artery ostia. Two patients had stenosis of the left
      anterior descending coronary artery, 1 of whom underwent successful internal
      thoracic artery grafting. CONCLUSIONS: Surgical angioplasty of the coronary stems
      restores physiologic coronary perfusion and conserves bypass material. It can be
      performed safely in children and provides encouraging midterm results.

PMID- 9918978
TI  - Bilateral sequential lung transplantation without sternal division eliminates
      posttransplantation sternal complications.
AB  - OBJECTIVE: The objective of this study was to assess the efficacy and safety of
      an alternative surgical incision for bilateral sequential lung transplantation.
      The vast majority of these operations worldwide have been performed through an
      anterolateral thoracosternotomy known as the "clamshell" incision. Recently, we
      have undertaken most of these operations through bilateral anterolateral
      thoracotomies without sternal division. METHODS: Our medical center performed 262
      bilateral sequential single lung transplantations from 1989 to April 1998.
      Between July 1996 and April 1998 we performed 69 bilateral sequential single lung
      transplantations on 68 recipients with 52 transplantations being conducted
      without initial sternal division. We retrospectively reviewed the results of
      these operations to assess the safety of the altered exposure and the efficacy in
      avoiding sternal wound complications such as malunion, dehiscence, osteomyelitis,
      and migrating hardware. Comparison was made to a historical control group
      composed of the last 50 patients in whom the full clamshell incision was used.
      RESULTS: Of the 68 patients who underwent transplantations, 52 patients underwent
      the initial exploratory procedure without sternal division. Two patients required
      emergency sternal division for institution of cardiopulmonary bypass to control
      life-threatening bleeding. Eleven of 68 patients were placed on bypass electively
      to permit transplantation, and the lack of a sternotomy in 8 patients did not
      present an obstacle to ascending aortic and right atrial cannulation. There were
      no wound healing complications in the 50 patients for whom the sternum was left
      intact. In a historical control group of 50 patients who underwent
      transplantation with sternal division, 34% experienced morbidity or mild
      disability as a direct result of poor sternal healing. CONCLUSIONS: We conclude
      that bilateral anterolateral thoracotomy without sternal division is a safe
      approach that allows adequate exposure without the risk of commonly observed
      problems with sternal healing.

PMID- 9918979
TI  - Acute brain death alters left ventricular myocardial gene expression.
AB  - OBJECTIVES: The depressed myocardial function observed in brain dead organ donors
      has been attributed to massive sympathetic discharge and catecholamine
      cardiotoxicity. Because elevated catecholamines are associated with altered
      myocardial gene expression, we investigated whether acute brain death from
      increased intracranial pressure alters the expression of myocardial gene products
      important in contractility. METHODS: A balloon expansion model was used to
      increase intracranial pressure in rabbits (n = 22). At timed intervals after
      brain death, mean arterial pressure, heart rate, electrocardiograms, histologic
      myocardial injury, and systemic catecholamines were assessed. Messenger RNA
      levels encoding myofilaments, adrenergic receptors, sarcoplasmic reticulum
      proteins, transcription factors, and stress-induced programs were measured with
      blot hybridization of total left ventricular RNA. RESULTS: Increased intracranial
      pressure induced an immediate pressor response that temporally coincided with
      diffuse electrocardiographic ST segment changes. Systemic epinephrine and
      norepinephrine levels concurrently increased (5- to 8-fold within 1 minute), then
      fell below baseline within 2 hours, and remained depressed at 4 hours. By 1 hour,
      histologic injury was evident. Four hours after the induction of increased
      intracranial pressure, levels of messenger RNA-encoding skeletal and cardiac
      alpha-actins, egr-1, and heat shock protein 70 were significantly increased. Sham
      operated animals did not exhibit these changes. CONCLUSIONS: Select changes in
      myocardial gene expression occur in response to increased intracranial pressure
      and implicate ventricular remodeling in the myocardial dysfunction associated
      with acute brain death.

PMID- 9918980
TI  - Vesnarinone and amrinone reduce the systemic inflammatory response syndrome.
AB  - OBJECTIVE: The systemic inflammatory response is an important cause of organ
      dysfunction. The present study tested the hypothesis that 2 clinically used
      agents, amrinone and vesnarinone, would decrease inflammation and cardiac
      dysfunction in a relevant model of systemic inflammatory response activation.
      METHODS: Rabbits received intravenous endotoxin, alone or in conjunction with
      amrinone or vesnarinone. Systemic effects were assessed by death, fever,
      behavior, and acidosis. Measures of inflammatory signaling were (1) plasma tumor
      necrosis factor-alpha and interleukin-1 beta production, (2) lung tissue
      myeloperoxidase activity, and (3) myocardial inducible nitric oxide synthase
      activity. Indices of systolic and diastolic myocardial function were measured in
      Langendorff-perfused hearts. RESULTS: Vesnarinone, in particular, reduced
      mortality rates (19% vs 61% for lipopolysaccharide alone, P =.01) and acidosis in
      lipopolysaccharide-treated rabbits. Both agents markedly reduced systemic tumor
      necrosis factor and interleukin-1 concentrations, lipopolysaccharide-mediated
      effects on myocardial systolic and diastolic function and on myocardial inducible
      nitric oxide synthase activity. Vesnarinone, but not amrinone, (1) decreased
      fever and lethargy, consistent with decreased central nervous system effects of
      endotoxin, and (2) decreased lung leukocyte infiltration. CONCLUSIONS:
      Vesnarinone and amrinone, which are used clinically for their inotropic and
      vasodilating properties, may be useful to limit inflammatory activation and
      consequent organ dysfunction. Structure-activity and/or pharmacokinetic between
      the compounds may be important, particularly in preventing inflammatory signaling
      within certain tissues.

PMID- 9918981
TI  - Ischemic preconditioning attenuates postischemic coronary artery endothelial
      dysfunction in a model of minimally invasive direct coronary artery bypass
      grafting.
AB  - OBJECTIVE: Unmodified reperfusion without cardioplegia in minimally invasive
      direct coronary artery bypass grafting procedures causes endothelial dysfunction
      that may predispose to polymorphonuclear neutrophil-mediated myocardial injury.
      This study tested the hypothesis that ischemic preconditioning in a minimally
      invasive direct coronary artery bypass grafting model attenuates postischemic
      endothelial dysfunction in coronary vessels. METHODS: In anesthetized dogs, the
      left anterior descending coronary artery was occluded for 30 minutes and
      reperfused for 3 hours without ischemic preconditioning (no-ischemic
      preconditioning; n = 7); in 7 dogs, the left anterior descending occlusion was
      preceded by 5 minutes occlusion followed by 5 minutes of reperfusion. Relaxation
      responses to stimulators of nitric oxide synthase were used to evaluate
      endothelial function in arteries from the ischemic-reperfused (left anterior
      descending) and nonischemic (left circumflex coronary artery) zones. RESULTS:
      Stimulated endothelial-dependent relaxation of epicardial left anterior
      descending artery to incremental concentrations of acetylcholine in the no
      ischemic preconditioning animals was shifted to the right, and maximal relaxation
      was attenuated compared with the nonischemic left circumflex coronary artery
      (117% +/- 4% vs 138% +/- 5%). In contrast, acetylcholine-induced maximal
      relaxation was comparable in the left anterior descending artery versus left
      circumflex coronary artery in the ischemic preconditioning group (130% +/- 6% vs
      135% +/- 5%). In 150- to 200- microm left anterior descending microvessels, 50%
      relaxation occurred with a lower concentration (log[M]) of acetylcholine in
      ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0
      +/- 0.1) with no group differences in smooth muscle relaxation to sodium
      nitroprusside, suggesting endothelial-specific damage. Adherence of fluorescent
      labeled polymorphonuclear neutrophils to epicardial coronary artery endothelium,
      used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil
      function, was significantly attenuated by ischemic preconditioning versus no
      ischemic preconditioning (293 +/- 25 polymorphonuclear neutrophils/mm2 vs 528 +/-
      29 polymorphonuclear neutrophils/mm2). CONCLUSION: In this minimally invasive
      direct coronary artery bypass grafting model, both agonist-stimulated and basal
      postischemic endothelial dysfunction were attenuated by ischemic preconditioning.

PMID- 9918982
TI  - Orthotopic cardiac transplantation after minimally invasive direct coronary
      artery bypass.

PMID- 9918983
TI  - Short-term effect of cyclosporine on circulating adrenomedullin after heart
      transplantation.

PMID- 9918984
TI  - Isolated atrioventricular discordance with solitus viscera, inverted atria, D
      loop ventricles, and solitus normally related great arteries: report of a rare
      case with successful surgical management.

PMID- 9918985
TI  - Reimplantation of anomalous left coronary artery on a beating heart.

PMID- 9918986
TI  - Videothoracoscopic treatment of postpneumonectomy empyema.

PMID- 9918987
TI  - Conservative treatment of tracheal rupture.

PMID- 9918988
TI  - [Clinical microbiology: a specialty in crisis?].

PMID- 9918989
TI  - [Bacterial meningitis in the health sector of Virgen del Rocio, Spain].
AB  - BACKGROUND: The aim of this study was review the epidemiology of the bacterial
      meningitis in our area. MATERIAL AND METHODS: A retrospective study was carried
      out of all the cases of bacterial meningitis in children with ages between two
      months and fourteen years, admitted in our hospital between 1986 and 1997. The
      following variables we analyzed: Sex, age of the patient, yearly and monthly
      incidence, previous antibiotic therapy, length of hospital stay, and analytical
      data of blood and cerebrospinal fluid. RESULTS: In the 755 cases analyzed, the
      50% correspond to bacterial meningitis, the 47.6% to viral or aseptic and 2.3% to
      tuberculous. In of the bacterial meningitis Neisseria meningitidis was isolated
      in 55.7% of cases, Haemophilus influenzae in 20.4%, Streptococcus pneumoniae in
      5.5%, other bacterias in 3.4%, and in 14.5% was not isolated any bacteria. We are
      assisting to an increase of Neisseria meningitidis serotype C during the last
      years. Haemophilus influenzae represents a more percentage of bacterial
      meningitis that in prior years. In meningitis by Streptococcus pneumoniae we
      observe a clear association with risk factors in children older than 2 years.
      CONCLUSION: Neisseria meningitidis is the main etiologic agent in children. The
      vaccination against Haemophilus influenzae serotype b and Neisseria meningitidis
      A and C can change the epidemiology in next years.

PMID- 9918990
TI  - [Study of the viral etiology of lower respiratory tract infections in a neonatal
      unit].
AB  - OBJECTIVE: To study the possible viral etiology in 139 infants with lower
      respiratory tract infection who required hospitalization in the Infant Unit of
      our hospital, from October 1994 to June 1995. PATIENTS AND METHODS: 139 patients
      were admitted, aged from 13 days to 14 months, during this period. The
      etiological agent was detected by direct immunofluorescence from nasopharyngeal
      secretions. Monoclonal antibodies were used against Respiratory Syncitial Virus,
      Influenza A Virus, Influenza B Virus, Adenovirus and Parainfluenza 3 Virus.
      Antibody detection against these viruses by Complement Fixation Test was done on
      29 of these patients, with paired sera (acute and convalescent phase). RESULTS:
      In 82 patients (59%) we found at least one viral agents from the nasopharyngeal
      specimens, but in 64 of these only one was detected, in the remaining 18, there
      were more than one. Significant levels of antibodies were detected in only six of
      the 29 patients tested. Serology was negative in the remaining 23 patients.
      CONCLUSIONS: Syncitial Respiratory Virus is the first virus responsible for the
      lower respiratory tract infection in this age group (49%). There was no
      correlation between serological diagnosis and antigen detection.

PMID- 9918991
TI  - [Prevalence of hepatitis C virus genotypes: epidemiology and histologic
      characteristics].
AB  - OBJECTIVE: To analyse the prevalence of HCV genotypes among patients from Gran
      Canaria and the relation with the routes of viral transmission, date of
      primoinfection and severity of hepatic lesion. PATIENTS AND METHODS: 179 patients
      were studied. In 61 patients the date of exposure was determinate. Liver biopsies
      were obtained in 139 patients. Genotypes were determinate by reverse
      hybridisation using InnoLiPA genotyping kit (Innogenetics). RESULTS: The
      distribution of genotypes was: 1b, 114 (63.7%), 1a, 30 (16.7%); 1, 17 (9.5%); 3a,
      7 (3.9%); 4c/4d, 6 (3.3%); 2, 1 (0.5%); 2a/2c, 2 (1.1%), 3, 1 (0.5%) and 4f, 1
      (0.5%). We did not find any case of coinfection with a second genotype. In
      univariable analysis, we found statistically differences in sex (78.9% of women
      infected with genotype 1b compared with 55.1% of men, p < 0.01 and 31.6% of men
      infected with 1a, 3a and 4c/4d compared with 15.7% of women, p < 0.01) and age
      (median age in genotype 1b 45 +/- 12 years vs 36 +/- 9 years in the other
      genotypes, p < 0.01). HCV subtypes 1a and 3a were predominant in patients IVDA
      (47.6% and 23.85% respectively) and 1b in blood transfusion receptors (71.2%) (p
      < 0.01). In 40.2% of the patients, the sources of infection were unknown. In the
      multivariable logistical regression analysis we found the only factor influencing
      the genotypes distribution was the transmission mechanism (p < 0.001) and sex and
      age are relationated with the transmission mode. The media infection duration in
      patients infected with 1b was 22 +/- 11 years vs 9 +/- 6 years in the other
      genotypes. We found differences in the liver histologic findings and the age of
      the patient, but not in the different genotypes. CONCLUSIONS: Our study reflects
      the higher frequency of HCV subtype 1b in our area and a different prevalence of
      genotypes in relation to mode of transmission. Our results suggest that in our
      media the liver damage seems to be directly influenced by the age of the patient,
      but not influenced by HCV genotype.

PMID- 9918992
TI  - [Ribotypes of strains of Pseudomonas aeruginosa in a patient with cystic
      fibrosis].
AB  - BACKGROUND: Pseudomonas aeruginosa is the major causative agent of respiratory
      infection in cystic fibrosis (CF) patients, and its presence in sputum is related
      with important deterioration of lung function in affected patients, thus a
      methodical monitorization and control of such a microorganism is decisive in the
      clinical status of the patient. Due to the limited effectiveness of phenotypic
      subtyping techniques, it is necessary to use molecular characterization methods.
      MATERIAL AND METHODS: We have studied the respiratory secretions periodically
      obtained over a period of time of 19 months, screening for total bacterial
      counts, P. aeruginosa load and genomic analysis of isolates using a ribotyping
      protocol. RESULTS: This study has showed the chronical and transitory carriage of
      different strains and the relation of increased bacterial counts with clinical
      deterioration periods. CONCLUSIONS: We consider that the use of molecular markers
      can be of great interest in the epidemiological surveillance of P. aeruginosa in
      CF patients.

PMID- 9918993
TI  - [Domiciliary intravenous antibiotic therapy].
AB  - BACKGROUND: To assess the efficiency and safety of intravenous antibiotic therapy
      (IAT) when performed through the traditional simple infusion system by gravity in
      the home setting. PATIENTS AND METHODS: The clinical records of patients
      undergoing intravenous antibiotic therapy through the traditional gravitational
      infusion system in the home care unit over a five year period were reviewed
      retrospectively. RESULTS: 120 patients were treated (44 F/76 M), with a mean age
      of 48 years (44-52). 67% of the total had chronic diseases. Infections were most
      commonly found in bones and joints (38%), followed by the skin and soft tissues.
      A wide variety of antibiotics was used, 61% as monotherapy. 76% of them were
      given intermittently. 161 intravenous catheters were used, 53% of which were
      central catheters with peripheral insertion, 27% inserted centrally and 20%
      peripheral catheters. The overall incidence of phlebitis was 18% without
      associated bacteremia. 91% of our patients evolved well, 6% had to become in
      patients, none of them due to problems with the infusion system or by their own
      petition. The intravenous treatment lasted a mean of 17 days at home and 25 days
      at both home and hospital, which represents a decrease of 2,040 hospital stays.
      CONCLUSIONS: The traditional gravitational system of infusion is an effective and
      safe method for intravenous antibiotic administration at home. For these
      therapies to be successful, suitable patients must be selected and continuous
      attention is required. This treatment at home satisfies the patient and permits
      hospital stays to be reduced, thus improving the use of hospital resources.

PMID- 9918995
TI  - [Microbiologic, pharmacokinetic and clinical aspects of the new 14 and 15 atom
      macrolides].

PMID- 9918994
TI  - [Eradication of Helicobacter pylori by triple therapy in ulcerous patients: the
      role of endoscopy and antibiotic sensitivity].
AB  - BACKGROUND: A protocol was conducted to evaluate the compliance and results of
      Helicobacter pylori infection treatment in patients with ulcer disease. To know
      the metronidazole, clarithromycin and amoxicillin activities of Helicobacter
      pylori strains from such patients. PATIENTS AND METHODS: 35 patients with ulcer
      disease (27 duodenal ulcer and 8 gastric ulcer) were studied. Diagnosis of
      Helicobacter pylori infection was performed by urease test and culture of mucosal
      gastric samples from patients undergoing endoscopy. The patients received the
      following treatment during 7 days: omeprazole (20 mg bid), clarithromycin (500 mg
      bid) and amoxicillin (1 g bid), OCA x 7. Susceptibility was determined by E-test
      system on Wilkins-Chalgren blood agar and read after 5 days. RESULTS: 22/24
      patients who had completed the protocol design eradicated Helicobacter pylori
      (91.7%), 11 patients (31.4%) refused second endoscopy to verify control of
      eradication. After treatment 10 patients presented with pyrosis "de novo" (28%).
      The overall metronidazol, claritromycin and amoxicillin resistance rate was 50%,
      1.5% and 0% respectively. CONCLUSIONS: OCA x 7 treatment obtains a eradication
      rate higher than 90% in our patients with ulcer disease, despite smoking habit,
      but with a significative number of patients presenting pyrosis after treatment.
      We recommend a non-endoscopy method to verify eradication rate, because of its
      poor acceptance. 3. Metronidazol resistance rate is high in our series but
      clarithromycin susceptibility is maintained.

PMID- 9918996
TI  - [Fungemia in an immunodepressed pediatric patient].

PMID- 9918997
TI  - [Sinusitis produced by fly larva].

PMID- 9918998
TI  - [Decontamination of gastroscopies with glutaraldehyde].

PMID- 9918999
TI  - [Isolation of Scedosporium prolificans in patients with cystic fibrosis].

PMID- 9919000
TI  - [Pleural empyema by Streptococcus mitis].

PMID- 9919001
TI  - [Therapeutic failure wtih chloroquine and primaquine in malaria by Plasmodium
      vivax].

PMID- 9919002
TI  - [Meningitis by Aeromonas sobria following cranio-encephalic traumatism].

PMID- 9919003
TI  - [Primary psoas abscess by Staphylococcus aureus and Mycobacterium tuberculosis].

PMID- 9919004
TI  - [The usefulness of the shell-vial culture in the diagnosis of cytomegalovirus
      infection in renal transplantation patients].

PMID- 9919005
TI  - [Pneumonia by Neisseria meningitidis: apropos of a case].

PMID- 9919006
TI  - [Hyperinfection by S. stercoralis: membranous glomerulonephritis, double
      bacteremia and petechiae exanthema].

PMID- 9919008
TI  - Efficacy of a Bacillus sphaericus formulation as influenced by the quality of
      Culex quinquefasciatus breeding waters.
AB  - To understand the physico-chemical factors that influence the efficacy of B.
      sphaericus formulation in the breeding sites of Culex quinquefasciatus, a study
      was carried out in Mayiladuturai area of Tamil Nadu (India). The factors studied
      were hydrogen ion concentration (pH), acidity, alkalinity, chlorides, phosphates,
      total hardness, sulphates, total solids, dissolved solids, suspended solids,
      nitrate nitrogen, ammoniacal nitrogen, dissolved oxygen, biological oxygen demand
      (BOD) and chemical oxygen demand (COD). Efficacy of the formulation was assessed
      in terms of reduction in larval population in the treated habitats. pH of water
      in the treated sites was around neutral range (mean +/- SD 7.65 +/- 0.23).
      Phosphate content was low (2.27 +/- 1.34 ppm) whereas chlorides (326.1 +/- 55.8
      ppm) and sulphates (38.9 +/- 23.8 ppm) were high. Total hardness ranged from 206
      to 462.5 ppm with a mean of 312.1 +/- 80.5 ppm. The chlorides and sulphates,
      though present in considerable quantity, did not have any influence on the
      efficacy of B. sphaericus formulation. However, the proportion of insoluble
      chlorides and sulphates which contribute to total hardness seemed to influence
      the formulation adversely.

PMID- 9919007
TI  - Association of hepatitis C virus & hepatitis B virus in chronic liver disease.
AB  - Hepatitis C virus (HCV) as a cause of chronic liver disease (CLD) was assessed by
      testing anti-HCV antibodies in the serum samples of 55 patients of chronic
      hepatitis (17), cirrhosis (32) and hepatocellular carcinoma (6). All the samples
      were also tested for the presence of HCV RNA by reverse transcription polymerase
      chain reaction (RT-PCR) using primers from the 5' non-coding region (NCR) and the
      relationship between the serological parameters and presence of HCV RNA was
      studied. The association of hepatitis B virus (HBV) with HCV in this group was
      evaluated by testing for the anti HBc antibodies (IgG and IgM separately) and
      HBsAg. The biochemical parameters and involvement of other risk factors were also
      studied. Twenty two (40%) patients were found to be HCV positive and 17 (77.3%)
      of these had evidence of infection or past exposure to HBV. On comparing the
      sensitivities of ELISA with that of PCR for the detection of HCV, we observed no
      significant difference between the two methods (P > 0.05, McNemar's test).
      Eighteen patients had no evidence of HBV or HCV infection. Our results indicate
      that HCV is next only to HBV in the causation of CLD. It is suggested that RT-PCR
      be used with antibody detection by ELISA for reliable detection of HCV infection.

PMID- 9919009
TI  - Diet induced thermogenesis with oral & intravenous feeding in chronically
      undernourished human subjects.
AB  - The parasympathetic nervous system (PNS) has been shown to be important in the
      mediation of diet induced thermogenesis (DIT). Chronically energy deficient (CED)
      subjects have a high resting parasympathetic tone, which could lead to a greater
      than expected DIT. DIT was studied in chronically energy deficient adult men and
      healthy age-matched volunteers (6 controls, 7 CED subjects) with an isocaloric
      (600 kcal) meal given by the oral and intravenous (i.v.) routes on two
      consecutive days, on a crossover basis. The resting metabolic rate (RMR) and the
      DIT were measured over 6 h, along with cardiovascular, biochemical and
      anthropometric parameters. Anthropometrically (height, weight, fat free mass,
      body mass index, mid upper arm circumference and sum of skinfolds), the CED group
      differed significantly from the well-nourished control group. There were no
      significant differences between the two groups in the basal state for metabolic
      (RMR, oxygen consumption, respiratory quotient), cardiovascular [blood pressure
      (BP), heart rate, cardiac output], and biochemical (plasma glucose, insulin and
      norepinephrine) parameters. The CED group had a significantly higher DIT response
      for both meal types when compared to the controls, when expressed as an absolute
      value and as a percentage response. However, the response was not significant
      when corrected for the meal size and body weight. There were also no significant
      differences between the two meal types in each group for the metabolic,
      cardiovascular and biochemical parameters during the DIT period, although, in
      general, the oral meal gave a larger DIT response compared to the i.v. meal. Both
      groups predominantly oxidised fat during the fasted stage and switched to
      carbohydrate oxidation when fed. It appears that, the previously demonstrated
      higher tone in the PNS, does not make a significant contribution to the thermic
      response of a meal in these subjects.

PMID- 9919010
TI  - Histologic chorioamnionitis & its association with prematurity in a hospital
      based study.
AB  - This prospective study was undertaken to study the occurrence of histologic
      chorioamnionitis and determine its association with prematurity; and to assess
      whether colonization of the genital tract of pregnant women by genital
      mycoplasmas or Chlamydia trachomatis is a risk factor for histologic
      chorioamnionitis. A total of 268 women with singleton pregnancies of over 26
      weeks gestation were subjected to high vaginal cultures of genital mycoplasmas
      and endocervical specimens for chlamydia antigen. Placental histopathology was
      performed on multiple sections. Histologic chorioamnionitis was documented in
      22.4 per cent (60/208) placentae. Genital tract colonization with Ureaplasma
      urealyticum or C. trachomatis was not a risk factor for histologic
      chorioamnionitis. Neonates born in association with histologic chorioamnionitis
      had a mean birth weight 111 g lower than those born without this lesion (2626.9
      +/- 702 g vs 2737.8 +/- 500 g, NS). The relative risk (95% confidence interval)
      of prematurity in the presence of histologic chorioamnionitis was 1.49 (0.87
      2.53). Analysis of linear trend in proportions for prevalence of histologic
      chorioamnionitis with decreasing gestation showed a significant association (P =
      0.047, 1-tail). These results taken together suggest that histologic
      chorioamnionitis may be a risk factor of prematurity, but of only a modest
      magnitude.

PMID- 9919011
TI  - Relationship of rectal & hippocampal temperature profiles to seizure activity in
      rats prone & resistant to hot water induced epilepsy.
AB  - The present study evaluates the relationship of seizure proneness, to core body
      and brain temperature following hot water stimulation with water of 55 degrees C
      in freely ambulant rats. The rectal and hippocampal temperatures were recorded in
      40 rats with bathing that included the head, while 10 other rats had similar
      thermal stimulation, but of the body alone. Bipolar stainless steel electrodes
      were stereotactically implanted into the dorsal hippocampal regions which served
      the dual purpose of recording the seizure discharges as well as regional brain
      temperature. It was observed that in the seizure prone (SP) rats, the mean rate
      of rise in rectal temperature was 1.5 degrees C/min, whereas in the seizure
      resistant (SR) animals it was 0.78 degree C/ min. However, there was no
      noticeable difference in the rate of rise in brain temperatures between the SP
      and SR groups, the rate of rise being 0.3 degree C/min. In the rats subjected to
      hot water bath over the body (excluding the head), there was no seizure activity.
      Further, there was no change in the brain temperature recorded in these rats,
      despite the rate of rise in rectal temperature being similar to that in the SP
      rats. These observations indicate that two thermoregulatory factors operate in
      seizure proneness-viz., a rapid rise in core body temperature; and a rise in
      local brain temperature. Both should coexist in order to elicit a hyperthermic
      seizure in rats.

PMID- 9919012
TI  - Trimodal distribution of HbS levels in sickle heterozygotes--an useful predictor
      of the alpha-genotype for population screening.
AB  - The trimodal distribution of HbS levels in sickle heterozygotes has been used as
      an indirect approach to determine the prevalence of alpha-thalassaemia in
      different population groups. We used this approach to predict the alpha-genotypes
      of 124 sickle cell heterozygotes where the HbS concentration varied from 20 to 46
      per cent with antimodes at 28.0 and 33.0. The alpha-genotypes in these
      individuals were also determined by Southern blot hybridization. We predicted
      homozygous (-alpha/-alpha) or heterozygous (-alpha/alpha alpha) alpha
      thalassaemia-2 in 78 subjects by the trimodal distribution of HbS. However,
      actual genotyping showed that 75 patients had alpha-thalassaemia. Forty six of
      the 47 subjects with a normal alpha-globin genotype (alpha alpha/alpha alpha)
      could be predicted indirectly. The overall sensitivity was 100 per cent and
      specificity was 94.2 per cent with a positive predictive value of 96.2 per cent
      and negative predictive value of 100 per cent. As alpha-genotyping is very
      expensive and not feasible in most laboratories in India, we conclude that the
      trimodal distribution of HbS levels is a suitable method for screening for alpha
      thalassaemia in population studies.

PMID- 9919013
TI  - Comparison of respiratory sensations induced by J receptor stimulation with
      lobeline in left handers & right handers.
AB  - We examined the hypothesis that right handers and left handers may differ in
      sensory perceptions and respiratory responses to J receptor stimulation with
      intravenous injections of lobeline HCl in incremental doses. The comparison was
      made between 6 right handers and 9 left handers (all males) for (i) the dose of
      lobeline required to produce sensory threshold (viz., first appearance of
      respiratory sensations) and cough threshold (first appearance of cough); and (ii)
      latency and duration of sensations for sensory and cough threshold. All these
      comparisons were not found to be significant statistically. The sensation of
      breathlessness, and feelings of drowsiness, giddiness and headache were perceived
      in 3 of the 9 left handers, and in none of the right handers, but the difference
      was not significant. Reflex bradycardia was recorded only in left handers (5 of
      9). The time (sec) for cough threshold was negatively correlated to threshold
      dose of lobeline (r = -0.5, and P < 0.05). The left handers perceived cough at
      the threshold as more distressing as compared with right handers (VAS P < 0.05).
      In conclusion, handedness did not influence J receptor responses to i.v.
      lobeline.

PMID- 9919015
TI  - Serogroups and antimicrobial susceptibility of clinical isolates of Salmonella
      species from a teaching hospital in Kuwait.
AB  - Salmonella strains isolated in a teaching-cum-general hospital in Kuwait during
      1990-1993 and 1996 were analysed to determine the trend in the prevalence of the
      serogroups and their changing pattern of susceptibility. The records were
      reviewed for all the 661 isolates encountered during these periods. The most
      prevalent serogroup in both children and adults was serogroup B, followed by
      serogroup C and D. A sizeable proportion of the strains were resistant to first
      line drugs. About 39% of the isolates were resistant to ampicillin, 17% to co
      trimoxazole, 13% to chloramphenicol, and 15% to cephalothin. The majority were,
      however, susceptible to the other drugs with low to very low resistance rates: 7%
      to amoxicillin/clavulanic acid, and 0.3% to cefotaxime. All the strains were
      susceptible to ciprofloxacin. In all, resistant strains were more prevalent among
      children than adults.

PMID- 9919014
TI  - The effect of two child-care practices of market women on diarrhoea prevalence,
      feeding patterns and nutritional status of children aged 0-24 months.
AB  - A cross-sectional comparative study was conducted in seven markets in Enugu and
      Nsukka, Nigeria, to evaluate the child-care practices, occurrence of diarrhoea,
      feeding patterns and nutritional status among 506 and 157 children aged 0-24
      months taken to the market (CTTM) by their mothers and those left at home (CLAH)
      respectively. A lack of a caretaker at home was the most common reason for taking
      children to the market. The majority (92%) of the caretakers at home were young
      (< 20 years). There was no difference in the occurrence of diarrhoea in the last
      month between the CTTM (39%) and the CLAH (41%) groups (p > 0.05). However, there
      were differences in reported diarrhoea episodes between children aged 0-6 months
      and higher age classes (chi 2 = 20.0; p = 0.003). Very few children (0.8%) were
      exclusively breastfed. More CTTM (58%) were still being breastfed than the 42% of
      CLAH (OR = 1.87; 95% C.I. = 1.27-2.37; p < 0.001). Children cared for at home had
      a slightly better but nonsignificant (p > 0.05) anthropometric status as
      characterised by weight-for-age and height-for-age. There was no relationship
      between feeding patterns and diarrhoea.

PMID- 9919016
TI  - Difficulties in conducting participatory action research to prevent diarrhoea in
      a slum area of Bangkok.
AB  - Childhood diarrhoea is a major cause of childhood morbidity and mortality in
      Thailand. During April 1988-April 1990, a study was conducted to evaluate
      participatory action research as a method of intervening on unhygienic practices
      in two communities in the Klong Toey slum of Bangkok (intervention group) and
      compared these practices in two other communities of the same slum where there
      was no intervention (control group). The following variables were compared in two
      groups: hygiene behaviour and factors associated with participation of community
      leaders and mothers with children aged less than five years. Two hundred and
      twenty-one mothers of the original 606 (36%) were still available at the end of
      the study. It was found that the mothers in the intervention groups were more
      likely to wash their hands before feeding and use cupboards and covered
      containers for keeping food. Several factors negatively affected community
      participation: matters concerning the slum culture and organization, community
      leadership, family problems, occupational problems, and physical environment of
      the community. The conclusions of the study are limited because of the
      considerable proportion of the subjects that was lost to follow-up. The study
      points at some of the methodological issues when conducting research in
      challenging and difficult to reach communities that have important health
      problems.

PMID- 9919017
TI  - Diarrhoea in children of Nigerian market women: prevalence, knowledge of causes,
      and management.
AB  - A cross-sectional survey was carried out among mothers of children aged less than
      five years in two markets in Ibadan, one with poor environmental sanitation and
      the other clean and well maintained. The study took place between September 1996
      and March 1997. The questionnaire used for this survey sought information about
      the occurrence of diarrhoea among children aged less than five years, their
      mothers' knowledge about the management of diarrhoea and their practices,
      including care-seeking practices, and the use of oral rehydration solutions. Two
      hundred and sixty-six mothers were interviewed in the first market (Bodija) and
      260 in the other (Gbagi). Thirty-seven percent of the children in the cleaner
      market (Gbagi) were said to have had diarrhoea within the last 3 months compared
      to 33% of the children in the unhygienic Bodija market (p > 0.05). These results
      suggest that environmental sanitation may not be a major determinant of diarrhoea
      among children of the two groups of market women. When their children had
      diarrhoea, 44% (Bodija) and 40% (Gbagi) of the mothers attended health centres,
      33% (Bodija) and 32% (Gbagi) gave ORT at home, and 12% (Bodija) and 19% (Gbagi)
      purchased drugs at a chemist. The study further showed that, while only one-third
      of all respondents resorted to home-treatment of diarrhoea with ORS, more than
      80% of them knew the components and composition of ORS solution. There is a need
      to continue to encourage mothers to use ORS and, thus, bridge the knowledge
      practice gap in mothers' management of diarrhoea at home.

PMID- 9919019
TI  - Bibliography on diarrhoeal diseases.

PMID- 9919018
TI  - An outbreak of food poisoning associated with restaurant-made mayonnaise in Abha,
      Saudi Arabia.
AB  - In May 1996, an outbreak of gastroenteritis occurred among customers who bought
      dinner from a restaurant that specialised in fried chicken in Abha city, south
      west Saudi Arabia. The median incubation period was 10 hours (range: 3 to 27
      hours). Of the 10 food items served, only mayonnaise (RR 2.52; 95% CI 1.71-3.73)
      and minced garlic (RR 1.20; 95% CI 1.02-1.41) were associated with cases.
      Salmonella enterica was isolated from 124 (84%) of the 159 persons with symptoms
      of food poisoning, and 91 (73%) were serogroup Enteritidis, phage type B 14.
      Mayonnaise was prepared in the restaurant using a regular blender. Minced garlic
      was prepared with the same blender immediately after making the mayonnaise.
      Unsafe storage of the mayonnaise at room temperature for a median of 6 hours
      could have resulted in overgrowth of bacteria and a high infective dose of
      bacteria per serving.

PMID- 9919020
TI  - Pew!

PMID- 9919021
TI  - A piercing issue.

PMID- 9919022
TI  - You pay a price.

PMID- 9919023
TI  - Posterior resin-based composites.

PMID- 9919024
TI  - Amalgam at the new millennium.

PMID- 9919025
TI  - How do we define longevity?

PMID- 9919027
TI  - Bleaching agents.

PMID- 9919026
TI  - Natural rubber latex.

PMID- 9919028
TI  - Safer drugs for children.

PMID- 9919029
TI  - New pathogen causes invasive infections.

PMID- 9919030
TI  - High doses of epinephrine may not be beneficial.

PMID- 9919031
TI  - Adverse drug interactions in dental practice. Professional and educational
      implications.
AB  - BACKGROUND: Rapid progress in dental pharmacotherapeutics requires that
      clinicians constantly update their knowledge of new drugs, drug interactions and
      useful therapeutic trends. This article is the first in a five-part series based
      on a 1998 International Association for Dental Research symposium entitled
      "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts."
      The goal of the series is to identify specific adverse drug interactions that are
      relevant to the therapeutic agents commonly used in general dental practice:
      analgesics, antibiotics, sedatives, local anesthetics and vasoconstrictors.
      METHODS: A group of dentist/clinical pharmacologists, with documented expertise
      in specific areas of dental therapeutics, reviewed the current literature
      regarding adverse drug interactions in dentistry. This expert panel evaluated the
      quality of information used to document these drug interactions and assess the
      severity of these drug reactions with respect to the drugs' use in dental
      practice. RESULTS: On the basis of the quality and severity of each reported
      interaction, the authors summarized the clinical importance of these drug
      interactions using a Significance Rating for Dental Drug Interactions. The
      participants presented their recommendations at the above-mentioned IADR
      symposium. CONCLUSIONS: Although thousands of drug interactions are described in
      the literature, the authors found many to be poorly documented or of minor
      importance to dental practitioners. For interactions that they determined to be
      relevant, the participants provided recommendations and precautions for
      preventing these potential complications. This article discusses the professional
      impact of drug interactions on dental practice; the classification and
      documentation of drug interactions; the determination of causality between drug
      interactions and adverse effects; risk factors; and unique characteristics of
      dental therapeutics. Subsequent articles will present specific summary
      recommendations for drug interactions associated with the use of antibiotics,
      analgesics, sedatives, and local anesthetics and vasoconstrictors. CLINICAL
      IMPLICATIONS: Although thousands of drug interactions have been reported in the
      literature, only a few are significantly associated with dental therapeutic
      agents. Avoiding these drug interactions will prevent potentially severe
      reactions in dental practice.

PMID- 9919032
TI  - Alveolar bone loss and tooth loss in male cigar and pipe smokers.
AB  - BACKGROUND: While cigarette smoking is recognized as being detrimental to oral
      health, the effects of cigar and pipe smoking on tooth-loss risk, alveolar bone
      loss and periodontal disease are not known. The authors conducted this study to
      determine whether cigar and pipe smokers were at greater risk of experiencing
      tooth loss and alveolar bone loss than were nonsmokers. METHODS: The authors
      studied 690 dentate men who participate in the Veterans Affairs Dental
      Longitudinal Study. Subjects are not VA patients, and they receive medical and
      dental care in the private sector. A board-certified periodontist conducted
      clinical examinations triennially for 23 years. These examinations included the
      number of teeth remaining, number of decayed and filled surfaces per tooth, and
      indicator scores for plaque, calculus, pocket probing depth, gingival bleeding
      and tooth mobility. Alveolar bone loss was assessed at each examination on
      intraoral periapical radiographs using the Schei ruler method, which measures
      loss of bone height in 20 percent increments. Multivariate analyses of tooth-loss
      rates and alveolar bone loss controlled for demographic and oral hygiene
      measures. RESULTS: The relative risk, or RR, of tooth loss compared with that of
      nonsmokers was significantly elevated in cigar smokers (RR = 1.3, 95 percent
      confidence interval, or CI, = 1.2, 1.5), pipe smokers (RR = 1.6, 95 percent CI =
      1.4, 1.9) and cigarette smokers (RR = 1.6, 95 percent CI = 1.5, 1.7). The
      percentages of mesial and distal sites with moderate-to-severe progression of
      alveolar bone loss (a change of 40 percent or more from baseline) were 8 +/- 1
      percent (mean +/- standard error) in nonsmokers, 16 +/- 3 percent in cigar
      smokers (P < .05), 13 +/- 4 percent in pipe smokers (P = .17), and 16 +/- 3
      percent in cigarette smokers (P < .001). Pipe and cigar smokers did not differ
      significantly from nonsmokers with respect to the percentage of sites at baseline
      with moderate-to-severe scores for calculus, pocket probing depth, gingival
      bleeding or tooth mobility. Pipe smokers had fewer sites with moderate-to-severe
      plaque accumulation than did nonsmokers (7 +/- 11 vs. 13 +/- 17, P < .05).
      CONCLUSIONS: The authors found that men who smoke cigars or pipes were at
      increased risk of experiencing tooth loss. Cigar smokers also were at increased
      risk of experiencing alveolar bone loss. These elevations in risk are similar in
      magnitude to those observed in cigarette smokers. CLINICAL IMPLICATIONS: The
      increases in risk related to cigar and pipe smoking provide a strong rationale
      for targeting smoking prevention and smoking cessation programs to smokers of all
      tobacco products.

PMID- 9919033
TI  - Dental unit waterlines: biofilms, disinfection and recurrence.
AB  - BACKGROUND: Transmission of microbial pathogens to patients from biofilm within
      dental unit waterlines, or DUWLs, is a concern. To reduce the risk of toxicity to
      dental patients when water coolants are used, numerous chemical agents have been
      tested. In a series of trials, the authors investigated the recurrence of
      microbial growth after treating DUWLs with sodium hypochlorite (bleach), or B;
      glutaraldehyde, or G; or isopropanol 15.3 percent, or I. METHODS: The authors
      excised tubing sections from dental units in a general clinic. The tubing
      sections were evaluated at baseline and after overnight treatment. Effluent water
      samples and biofilm samples from tubing sections also were evaluated, by culture,
      at baseline and after treatment with the chemical agents. Biofilm within the
      tubing was examined by scanning electron microscopy, or SEM, and the authors
      identified bacterial isolates using standard techniques. The authors performed
      minimum inhibitory concentration tests on identified isolates pre- and
      posttreatment and compared the results to determine possible differences in
      resistance. RESULTS: In baseline evaluations, the authors determined that the
      effluent and biofilm matrix harbored an average of 1 x 10(5) colony-forming
      units, or CFU, per square centimeter and 1 x 10(4) CFU/cm2 recoverable
      microorganisms, respectively. A single overnight treatment of the DUWLs with B, G
      or I rendered effluent and biofilm samples that were free of recoverable
      bacteria. The number of viable bacteria in the effluent and the biofilm of B- or
      I-treated DUWLs returned to pretreatment levels by day six and day 15,
      respectively. DUWLs treated with G showed evidence of bacterial recurrence in the
      effluent and the biofilm to pretreatment levels by day three. The authors
      compared recurrence of biofilm and effluent posttreatment with untreated control
      tubing. The lower recurrence of viable bacteria in both biofilm and effluent
      samples for tubing treated with B and I was significant (P < or = .05). No
      evidence of resistance to the agents was noted during the study. Multiple
      treatments held the bacterial population to below recoverable levels but failed
      to remove the biofilm matrix, as evidenced by SEM. CONCLUSIONS: B, G and I
      eliminated recoverable bacteria after treatment and inhibited their recurrence in
      DUWL. Recolonization rates varied by agent. CLINICAL IMPLICATIONS: The residual
      effect of these agents raises concerns about the slow release of potentially
      toxic substances from the residual biofilm matrix. These agents reduce
      microorganisms in effluent water but do little to destroy the biofilm matrix in
      the DUWL, even with periodic treatments. Bacterial populations in the dental unit
      water rapidly recolonize the DUWL. Chemical agents or agents that potentially
      could be trapped in the matrix can represent an additional risk to the patient.

PMID- 9919034
TI  - Referring adult patients for orthodontic treatment.
AB  - BACKGROUND: An increasing number of adults are undergoing orthodontic treatment,
      but they still make up only a small proportion of all adults who could benefit
      from such therapy. The purpose of this article is to illustrate the
      appropriateness and value of orthodontic treatment in adults. METHODS: The
      authors review and summarize previous studies regarding adult orthodontic
      treatment. Data from these studies are compared to determine the prevalence of
      orthodontic treatment in adults, the reasons why many adults do not seek
      treatment and the outcomes of orthodontic treatment in adults. In addition, the
      authors describe a case to demonstrate how a combination of orthodontic therapy
      and orthognathic surgery can facilitate and complement prosthetic rehabilitation.
      RESULTS: Numerous studies indicate that two-thirds to three-fourths of adults
      possess some form of malocclusion, yet adults make up only 15 percent of all
      orthodontic patients. Reasons given by adults for not seeking treatment include a
      lack of awareness that orthodontic treatment can be performed in adults,
      apprehension about possible pain or discomfort and concern about social
      acceptance. However, most patients who underwent orthodontic treatment reported
      only mild discomfort of one to two days' duration, and only 20 percent of
      patients felt that the appliances had an adverse social effect. Overall, patients
      reported high levels of satisfaction with treatment. Orthognathic surgery in
      addition to orthodontics may be required for the most severe problems, and is
      compatible with subsequent fixed and removable prosthetic treatment. CONCLUSIONS:
      Adjunctive and comprehensive orthodontic treatment is feasible for adults of all
      ages. Correction of malocclusion makes it possible to improve the quality of
      periodontal and restorative treatment outcomes, in addition to providing
      psychosocial benefits. CLINICAL IMPLICATIONS: General dentists are often the
      first dental professionals to suggest orthodontic treatment and to refer patients
      to orthodontic specialists. Moreover, with the growing emphasis on cosmetic
      dentistry, more adults are likely to seek information regarding orthodontic
      surgery. This article provides general dentists with the information needed to
      communicate with patients about treatment.

PMID- 9919035
TI  - Management of missing maxillary lateral incisors.
AB  - BACKGROUND: Missing maxillary lateral incisors create an esthetic problem with
      specific orthodontic and prosthetic considerations. The purpose of this article
      is to describe treatment protocols and problems encountered in the management of
      this disorder. CASE DESCRIPTION: The two common treatment options are orthodontic
      space opening for future restorations or orthodontic space closure using canines
      to replace the missing maxillary lateral incisors. The required amount of space
      opening and the various prosthetic options are discussed. The methods for
      reshaping canines in orthodontic space closure and building them up to simulate
      lateral incisors also are described. The indications, advantages and
      disadvantages of both treatment modalities are outlined to help clinicians make
      decisions in borderline situations. CLINICAL IMPLICATIONS: Teamwork between the
      orthodontist, general practitioner and restorative dentist is important when
      analyzing factors related to individual patients and establishing overall
      treatment plans. This also will allow treatment modalities and the various
      options for replacing missing maxillary lateral incisors in space opening to be
      discussed between team members and the patient.

PMID- 9919037
TI  - Using an old technique with modern materials to fabricate esthetic temporary
      restorations.

PMID- 9919036
TI  - Maxillary midline diastemas: a look at the causes.
AB  - BACKGROUND: Maxillary midline diastemas are a common esthetic problem that
      dentists must treat. Many innovative therapies have been used, varying from
      restorative procedures to surgery (frenectomies) and orthodontics. At times,
      these procedures have been performed by the dentist without full appreciation of
      the factors contributing to the diastemas. CASE DESCRIPTION: Before the
      practitioner can determine the optimal treatment, he or she must consider the
      contributing factors. These include normal growth and development, tooth-size
      discrepancies, excessive incisor vertical overlap of different causes,
      mesiodistal and labiolingual incisor angulation, generalized spacing and
      pathological conditions. A carefully developed differential diagnosis allows the
      practitioner to choose the most effective orthodontic and/or restorative
      treatment. CLINICAL IMPLICATIONS: The differential diagnosis leads to a treatment
      approach that most effectively addresses the patient's problem. By treating the
      cause of the diastema, rather than just the space, the dentist enhances both the
      patient's dental function and appearance.

PMID- 9919038
TI  - Ask the experts. What insurance coverage do I need?

PMID- 9919039
TI  - Assessing the efficacy and safety of an electric interdental cleaning device.
AB  - BACKGROUND: Although routine interdental cleaning is important and recommended by
      dental professionals, compliance has been relatively low. To aid in improving
      compliance, an electrically powered device has been developed. METHODS: This six
      month randomized, single-blinded, parallel-group study was conducted to compare
      the long-term efficacy and safety of a new interdental cleaning device (Braun
      Oral-B Interclean, model ID2) with those of an ADA-approved waxed dental floss in
      healthy adults. RESULTS: The authors found no statistically significant
      difference between the two products with respect to the gingival index or
      gingival bleeding index after three or six months of use. A one-time product use,
      at the six-month examination, confirmed the equivalency of the two methods with
      respect to removal of dental plaque. The oral soft-tissue status of both groups
      of subjects also remained comparable throughout the study. CONCLUSION: Use of the
      interdental cleaning device and dental floss resulted in comparable benefits with
      respect to gingival health and plaque removal. CLINICAL IMPLICATIONS: Although it
      was not shown to be an improvement over dental floss, the cleaning device was
      comparable in every respect. Since it can be used with one hand and does not
      require as much dexterity as floss, the device warrants consideration by those
      who lack the motivation or are unable to use dental floss.

PMID- 9919040
TI  - Does the mouth put the heart at risk?

PMID- 9919041
TI  - Dentistry's mission and the high-fee practice.

PMID- 9919042
TI  - DMSO contracting basics.

PMID- 9919043
TI  - Stereotactic breast biopsy: experience in a community setting.
AB  - This article reviews the first year experience with stereotactically guided
      percutaneous breast biopsy at Baptist Health Systems Women's Center. One hundred
      forty eight procedures were performed on one hundred forty one patients from July
      1997 through July 1998. Our biopsy program is a cooperative effort involving
      surgeons, radiologists, pathologists, and ancillary health care personnel. In
      accordance with published literature, we have found the procedure to be
      efficacious, safe, cost effective and well accepted by patients and physicians.
      The advantages and limitations of minimally invasive breast biopsy are discussed
      as well as our concept of the role of this technique in management of patients
      with an abnormal mammogram.

PMID- 9919044
TI  - Outpatient diabetes management of Medicare beneficiaries in four Mississippi fee
      for-service primary care clinics.
AB  - BACKGROUND: As part of a quality improvement initiative aimed at increasing
      physician compliance with standards of care for diabetes patients, diabetes
      practice patterns among Medicare beneficiaries in four primary care clinics were
      examined in Mississippi. METHODS: Retrospective chart reviews of Medicare
      beneficiaries with a diagnosis of diabetes were conducted to examine physician
      compliance with recommended diabetes monitoring services. RESULTS: Fifty-three
      percent of all beneficiaries did not have a recorded A1c test while 54 percent
      did not have a recorded foot exam. The percentage without foot exams decreased
      with quarterly visits. Seventy-two percent and 68 percent of patients had testing
      for lipids and proteinuria, respectively, although variability in types of
      testing performed was seen. Seventy-six percent of beneficiaries did not have a
      referral for a dilated eye exam. CONCLUSIONS: The study has uncovered, within
      several primary care sites in Mississippi, variable documentation of compliance
      with many clinically relevant recommendations relating to the care of elderly
      patients with diabetes. These items can be targeted for improvement as part of a
      statewide quality improvement initiative for Medicare beneficiaries.

PMID- 9919045
TI  - Thomas Jefferson's Y chromosome: the power and limitations of DNA analysis.

PMID- 9919046
TI  - Ichthyosis in a nutshell.

PMID- 9919047
TI  - Pediatric neck injuries.

PMID- 9919048
TI  - Puncture wounds.
AB  - Puncture wounds are common in children, and most are uncomplicated. For children
      who have a delayed presentation or signs of infection, consider the possibility
      of a retained foreign body. The diagnosis of P aeruginosa osteochondritis should
      be considered in any child who exhibits persistent signs and symptoms after
      puncture wounds; timely use of laboratory tests, radiologic imaging, and
      orthopedic referral is required.

PMID- 9919049
TI  - Gastroesophageal reflux.

PMID- 9919050
TI  - Index of suspicion. Case 1. Autoimmune chronic hepatitis.

PMID- 9919051
TI  - Index of suspicion. Case 2. Abdominal migraines.

PMID- 9919052
TI  - Index of suspicion. Case 3. Infantile botulism.

PMID- 9919053
TI  - Influenza update.

PMID- 9919054
TI  - Latex allergy.

PMID- 9919055
TI  - Medicare reimbursement and independent practice: the Utah example.

PMID- 9919056
TI  - Taking your patient base with you.

PMID- 9919057
TI  - Safeguarding patients under managed care.

PMID- 9919059
TI  - All that itches is not yeast.

PMID- 9919058
TI  - Chemoprevention trends in breast cancer.

PMID- 9919060
TI  - Ovarian cancer. It whispers ... so listen!

PMID- 9919061
TI  - An important risk group. Managing occupational HIV exposure.

PMID- 9919062
TI  - The elusive itch. Assessment, diagnosis and management of pruritus.

PMID- 9919063
TI  - A new age in Pap testing.

PMID- 9919064
TI  - The most common complication of pregnancy. Urinary tract infection.

PMID- 9919065
TI  - A new strategy is needed. Reducing unplanned pregnancies.

PMID- 9919066
TI  - Cutting through the hype. Hormone replacement therapy with DHEA.

PMID- 9919067
TI  - Advancing safe nursing practices.

PMID- 9919068
TI  - Continuous renal replacement therapy 21 years on.

PMID- 9919069
TI  - Tetanus--the silent killer: how safe are you?
AB  - Despite the fact that tetanus is entirely preventable, mortality and morbidity as
      a result of this disease remain significant. The tetanus toxoid is one of the
      most potent poisons known. While immunisation programs focus on children, the
      elderly remain at risk of contracting immunisable diseases. Tetanus often leads
      to prolonged hospital stays and requires emergency and intensive care
      intervention and management. This case study illustrates a number of important
      points concerning the recognition, treatment, management and prevention of
      tetanus poisoning, and highlights the importance of considering the immunisation
      status of our elderly patients.

PMID- 9919070
TI  - Neonatal nurses' views on the barriers to parenting in the intensive care nursery
      -a national study.
AB  - A descriptive research study was undertaken at a national level to identify
      neonatal nurses' views on the barriers to parenting in the intensive care
      nursery. The objective of the study was to determine nurses' responses to the
      barriers to parenting identified in the literature. Relevant literature was
      examined and a questionnaire developed and pilot tested. In all, 794
      questionnaires were distributed with neonatal nursing newsletters and in
      intensive care nurseries throughout NSW, the ACT, South Australia, Western
      Australia, the Northern Territory and Queensland. The Neonatal Nurses Association
      of Victoria and Tasmania did not respond to the invitation for its members to
      participate, so no questionnaires were distributed in these states. Neonatal
      nurses were asked to indicate the extent of their agreement with the issues
      identified in the literature on a four-point scale, with 1 the lowest score and 4
      the highest. Of the 794 questionnaires distributed 298 were returned,
      representing a 37.5 per cent response rate. The results of the questionnaire
      indicate nurses' understanding of the environmental and emotional barriers
      confronting parents; however, there was little acknowledgment of nurse-initiated
      practices which also prevent parents fulfilling their parenting role. Responses
      to several questions were evenly divided, indicating inconsistency in neonatal
      nurses' views on what constitute barriers to parenting. The results of the
      questionnaire provide a national snapshot of the views of neonatal nurses with
      respect to the barriers confronting parents as they attempt to fulfil their
      parenting role and bring nurse-initiated barriers, such as policies and
      procedures, to the attention of neonatal nurses.

PMID- 9919071
TI  - Critical care management of the patient with acute respiratory distress syndrome
      (ARDS). Part 2--A review of modes and strategies for ventilating the patient with
      poorly compliant lungs.
AB  - Mechanical ventilation strategies for patients suffering from acute respiratory
      distress syndrome (ARDS) have traditionally relied on volume cycling. Due to the
      poor lung compliance characteristic of ARDS, these patients may be exposed to
      very high inspiratory pressures to achieve sufficient tidal volumes for adequate
      gas exchange. This greatly increases the risk of ventilator-induced lung injury
      associated with alveolar over-distention. The literature review explores the
      rationales behind alternative ventilation modes and strategies introduced to
      reduce the risk of ventilator-induced lung injury for the patient with ARDS.

PMID- 9919072
TI  - Health service provision and education in rural Australia.

PMID- 9919073
TI  - Spinal cord injury rehabilitation outcomes: a comparison of agricultural and non
      agricultural workers.
AB  - This study of Victorian workers who sustained a spinal cord injury aimed to: (i)
      define the proportion of this population who were employed in an agricultural
      setting prior to sustaining their injury; (ii) explore the preinjury
      characteristics and postinjury vocational achievements of agricultural workers;
      and (iii) compare these with those of non-agricultural workers. Respondents were
      sampled from patients presenting for review at the participating spinal unit over
      the 9 months study period (N = 150 with a participation rate of 71%). Results
      indicated that while those working in agricultural occupations account for
      between 4 and 4.5% of Victorian workers, 13.3% of respondents reported working in
      agricultural occupations at the time of their injury. In spite of the physically
      demanding nature of their workplace many agricultural workers returned to farming
      postinjury. The rehabilitation experiences and return to work outcomes achieved
      by the agricultural workers were found to be very similar to those of other
      workers, despite the additional barriers they were expected to have encountered.

PMID- 9919075
TI  - Technology in education: what is appropriate for rural and remote allied health
      professionals?
AB  - Recent technological advances provide exciting opportunities for the delivery of
      education to rural and remote allied health professionals. Distance education
      modes can overcome barriers of distance and cost. However, the use of
      technologies may allow distance education to be more interactive for rural and
      remote professionals. Technologies that can be used are audioconferencing,
      videoconferencing, electronic mail (email), CD-ROM and the Internet. Combinations
      of any of these technologies and traditional forms of educational delivery are
      possible. The important objective is to create a learning environment that
      maximises interactivity and develops information literacy.

PMID- 9919074
TI  - Differences between metropolitan and country public hospital allied health
      services.
AB  - This paper compares patient and episode characteristics in allied health services
      delivered in country and metropolitan hospitals. Eight public hospitals (46
      allied health services) participated in the study (three country and five
      metropolitan sites, situated in South Australia, Queensland and Tasmania).
      Standardised rates of patient throughput were similar for country and
      metropolitan allied health services, despite smaller numbers of country staff
      providing services to larger geographical areas. Although the differences were
      not significant, country patients were generally older and had more chronic
      conditions than metropolitan patients. Fewer country patients than metropolitan
      patients were eligible for rebates in the private sector. In addition, fewer
      alternative services were available in country communities, which heightened the
      role of the public hospital outpatients services within the community. This paper
      provides an argument for similar funding arrangements for country and
      metropolitan ambulatory allied health services.

PMID- 9919076
TI  - Rural attachments for students in the health professions: are they worthwhile?
AB  - In the period 1991-96, 156 undergraduates from 14 health disciplines at the
      University of Sydney completed rural attachments in rural and remote areas of
      Australia as part of the Rural Careers Project. On return from their attachment,
      students were encouraged to write a brief report of their experiences. Ninety-two
      available reports were analysed as one means of assessing the success of the
      attachments with respect to informing students about rural health issues and
      stimulating their interest in rural careers after graduation. A content analysis
      of the students' written comments about their perceptions and experiences was
      completed. Students were extremely positive about the value of the attachments
      and expressed more positive than negative comments regarding their perceptions of
      rural life and work. The results show that rural attachments are indeed
      worthwhile learning opportunities.

PMID- 9919077
TI  - Evaluation of the provision of fieldwork training through a rural student unit.
AB  - A Rural Student Unit was established as a pilot project to trial a model of rural
      fieldwork placement provision. The Unit aimed to increase the number of student
      placements available in rural areas and provide undergraduate students with a
      positive fieldwork experience. The results indicate that the Unit was successful
      in overcoming some of the barriers to rural fieldwork, for both students and
      supervisors, and substantially increased the number of students undertaking
      fieldwork in this area. The results support the further trialing and expansion of
      the model.

PMID- 9919078
TI  - Health education activities conducted by physiotherapy students on field trips to
      rural areas: a case study.
AB  - Field trips to country communities have formed part of the final year
      physiotherapy undergraduate curriculum at the University of South Australia since
      1995. These trips have aimed to give students an experience in primary health
      care. This paper evaluates these activities within the framework of the health
      promotion model from the perspective of those involved and evaluates feedback
      from these people. The activities met four of the five criteria of the health
      promotion model to some degree. Evaluation from all those participating has been
      mainly positive, with some aspects of organisation of the field trips requiring
      improvement. All involved felt they had gained benefits from the field trips;
      however, further work is needed to align the activities with local health
      promotion infrastructure.

PMID- 9919079
TI  - Delimiting 'rural': implications of an agreed 'rurality' index for healthcare
      planning and resource allocation.
AB  - Rural and remote Australia is characterised by considerable geographical and
      social diversity. There is no 'natural' classification of what constitutes
      'rural' or 'remote', and precise definition of what is meant by the term 'rural'
      has proved to be an elusive goal. Nonetheless, it is recognised that the
      differentiation of rural areas has important implications for healthcare planning
      and the research that underpins it. Whether it be the development of resource
      allocation formulae that determine the provision, location and type of rural
      health services, measuring service utilisation rates as an indicator of need for
      services or health outcome measures, the way in which populations and communities
      are delimited as urban, rural and remote will always influence and sometimes may
      even determine the assessment. The time is ripe for the development of an agreed
      classification for the investigation of rural health issues.

PMID- 9919080
TI  - National Rural Health Alliance. Council of Australian Governments.

PMID- 9919081
TI  - Women & breast cancer.

PMID- 9919082
TI  - Reducing smoking among women. Year 2000 goal requires action today.

PMID- 9919083
TI  - The breast cancer prevention trial. Should Women at risk take tamoxifen?

PMID- 9919084
TI  - New digs for tiny tots. How Dartmouth Hitchcock Medical Center moved its NICU.

PMID- 9919085
TI  - Assessing competence. Meeting the unique needs of nurses in small rural
      hospitals.

PMID- 9919086
TI  - Help! I need a MEDLINE search!

PMID- 9919087
TI  - Discovering the leader within you. Developing leadership opportunities within
      every nursing role.

PMID- 9919088
TI  - Public relations for advanced practice nurses.

PMID- 9919089
TI  - Forging new frontiers. Annual convention spotlights future direction for nursing

PMID- 9919090
TI  - Surviving breast cancer. Women talk about their lives, their experiences.

PMID- 9919091
TI  - Some challenges to be faced when building capacity.

PMID- 9919092
TI  - The preterm labor experience: a balancing act.
AB  - The purpose of the study was to identify how women described, interpreted, and
      managed their preterm labor experience. Ten married, middle-class women
      participated in an in-depth, tape-recorded interview in the hospital after
      preterm labor was stabilized; periodically over the telephone after discharge
      from the hospital; and in the hospital, home, or via telephone after birth, for a
      total of 31 interviews. Using qualitative data analysis techniques, the findings
      were conceptualized as five recursive stages: becoming aware that something was
      wrong and feeling unbalanced, making sense of the experience as they sought to
      understand why preterm labor occurred, trying different strategies to re-create a
      balance in their lives, addressing other life stressors that threatened restoring
      balance, and emerging from the preterm labor experience with added growth. An
      increased understanding of the preterm labor experience from the women's
      perspective can be helpful to health care professionals and others who support
      women during pregnancy.

PMID- 9919093
TI  - Perceptions of caring. Comparison of antepartum and postpartum patients.
AB  - An exploratory, comparative survey design was used to describe and compare
      similarities and differences in perception of caring behaviors between
      hospitalized antepartum and short-stay postpartum patients. Forty-two patients
      completed the 63-item Caring Behavior Assessment instrument (CBA). The scale,
      based on Watson's theory of caring, contains seven categories. There were no
      statistically significant differences in age, education, gravida, or para between
      the two groups. Significantly more women in the postpartum group were married.
      There were no statistically significant differences or correlations in the total
      CBA scores and the demographic variables. No statistically significant
      differences in total CBA scores were found between antepartum participants and
      postpartum participants. These findings corroborate the results of "caring"
      studies in other patient populations, that satisfying basic needs--that is,
      evidence of technical knowledge and skills--is more important to patients than
      meeting higher order needs.

PMID- 9919094
TI  - Postpartum sleep in the hospital. Relationship to taking-in and taking-hold.
AB  - This descriptive, correlational study examined the relationship of sleep in the
      hospital to the new mother's progression through Rubin's phases of taking-in and
      taking-hold in 120 women who had delivered vaginally. The Martell and Mitchell
      Postpartum Questionnaire, which measured taking-in and taking-hold, was completed
      the evening of delivery and the following two mornings. The Verran and Snyder
      Halpern Visual Analog Sleep Scale was completed each morning. Both taking-in and
      taking-hold were present on the evening of delivery. There were small decreases
      in taking-in and small increases in taking-hold between the evening of delivery
      and the first morning. Sleep disturbance was high, and sleep effectiveness was
      low, on the first evening. Neither sleep measure was a predictor of change in
      taking-in or taking-hold. Findings indicate that taking-in and taking-hold are
      both present on the day of delivery and that increases in taking-hold take place
      despite high levels of sleep disturbance.

PMID- 9919095
TI  - The preparation of patients for cardiac surgery.
AB  - This study examines the impact of a preadmission telephone intervention on
      anxiety, knowledge, and readiness for discharge for patients attending a
      preadmission teaching program prior to cardiac surgery. The primary goal of the
      telephone intervention was to provide support by giving additional information
      about individual concerns. The telephone intervention did not have an effect on
      anxiety and knowledge. A significantly higher level of anxiety was found in the
      experimental group on admission, but this difference became nonsignificant when
      baseline level and length of waiting time were entered as covariates. The more
      anxious group rated their perceived knowledge level lower, despite the fact that
      both groups had similar scores in actual knowledge. Given the potential barrier
      that anxiety can pose for patient learning, nurses need to adapt their
      interventions to deal with the patients' feelings of anxiety that accompany
      cardiac surgery to make the learning process effective.

PMID- 9919096
TI  - After-the-fact strategies Mexican Americans use to prevent HIV and STDs.
AB  - Hispanics make up less than 10% of the U.S. population but account for 83,923
      (17%) of all U.S AIDS cases and are disproportionately affected by sexually
      transmitted diseases (STDs). Nurses have a mandate to provide culturally
      competent care, but to do so, they must understand what their clients' needs are
      and how best to deliver nursing care. A key finding of this exploratory focus
      group study with newly immigrated Mexican Americans in North Carolina was that
      respondents were actively striving to prevent HIV or STDs. Their preventive
      practices for both HIV and STDs centered around a "gonorrhea model" of prevention
      and casual transmission. The emphasis was not on the biomedical model of
      transmission or prevention (condoms use). The findings also suggested that the
      level of counseling for prevention needs to be targeted differently for men than
      for women.

PMID- 9919097
TI  - Individually reported effectiveness of therapy for chronic pain.
AB  - In 1996, a primary care-based multidisciplinary group model for treating patients
      with chronic pain was begun in a large HMO. Prior to the visits, patients
      completed an assessment, which included their description of previous and current
      therapies and their effectiveness (inventory developed by A. G. Lipman). This
      article describes the reports of the first 163 patients. Females were referred
      three times more often than males; the average age was 52 (range 18 to 88);
      average years in pain = 11 (range 0.3-50). Most patients reported more than one
      source of pain. No therapy was reported to be effective for everyone; what was
      highly effective for one could actually increase pain in another. Side effects
      caused patients to discontinue even effective therapy. Costly does not mean more
      effective. It is, therefore, essential that a systematic process of accessment,
      evaluation, and titration be employed with every intervention.

PMID- 9919098
TI  - Contesting competency: cultural safety in advanced nursing practice.
AB  - A central tenet of the competency approach to nursing education and regulation is
      that it ensures the safe care of clients and communities with whom nurses work.
      However, the competency approach is problematic in its conception and application
      to nursing. Incorporation of this framework into advanced practice requires that
      its limitations are acknowledged so that current interpretations and applications
      can be challenged and resisted. Through exploring the concept of cultural
      competence some of the problems associated with the application of the competency
      approach to professional nursing practice will be exposed. The issues revealed in
      this exploration prompt the question whether the competency framework is the best
      way to ensure competent professional practice.

PMID- 9919099
TI  - Dementia care. How nurses rate.
AB  - The aim of this qualitative research was to invite home carers to share their
      perceptions of the quality of nursing care they witnessed their relative with
      dementia receive, when he or she was admitted to an acute care setting for an
      acute illness episode or other health related concern. Twenty participants were
      recruited through the local Alzheimer's Support Groups and newspapers.
      Biographical data were collected relating to the carer's and relative's age,
      gender, nature of relationship, date of Alzheimer's diagnosis, period of
      domiciliary care, and existing psychosocial and economic support systems. Each
      carer was interviewed for about one hour, to allow sufficient time for
      recollection of memories of hospitalisations within the previous 12 months. The
      semistructured interviews were audiotaped for verbatim transcription. Computer
      assisted thematic analysis identified themes and sub-themes regarding aspects of
      nursing care that home carers witnessed with which they were pleased and not
      pleased. Based on the home carers' accounts recommendations were made for nurses
      relating to improving the care of people with dementia in acute care settings.

PMID- 9919100
TI  - Perceptions of clinical role modelling: an exploration of nursing students'
      experiential learning.
AB  - The purpose of this study was to reveal the essence of role modelling in relation
      to learning in the clinical field from the nursing student's perspective. Twenty
      one final year nursing undergraduates voluntarily and purposefully participated
      as informants in the study. Each participated in a face-to-face interview with a
      nurse researcher. In addition, a focus group interview session was conducted with
      seven of the participating students. Using the phenomenological method, the
      essence of role modelling emerged as a core theme which was linked to the
      students' clinical learning experiences. Multi-dimensional elements of learning
      that were contingent upon role modelling were categorised into five major themes:
      Expectations of self and others; Situational conditional factors; Situational
      anxiety--reality of fear/nervousness; Application of theoretical knowledge to
      practice; and, Experiential knowledge--an active learning process. The students'
      experiences of how role modelling impacted on their learning has implications for
      nursing education. It is necessary to acknowledge the variety of health carers,
      and in particular, the clinical nurse educator, who have consequential influences
      on student learning in the clinical field.

PMID- 9919101
TI  - Study--hassles and rewards.

PMID- 9919102
TI  - The ancient Greek health belief model

PMID- 9919103
TI  - Assisted reproduction: who qualifies?
AB  - Assisted reproductive technologies (ARTs) have been the focus of considerable
      debate in which a range of social issues has been addressed, yet the question of
      who is eligible for ART, who can get access, who is excluded and by what means,
      has received little attention in comparison with other issues. In Australia
      social policies presently exist in some (but not all) states which address this
      question, however several recently publicised cases have highlighted the need for
      an examination of inclusion/exclusion practices from a social justice
      perspective. This paper seeks to explore the issue of access and eligibility for
      ART with a particular interest in exposing the contradictions, inconsistencies
      and assumptions inherent in arguments put forward for particular inclusions and
      exclusions. It is my contention that social policy relating to criteria for
      eligibility and access to ART invests the medical profession with a gatekeeping
      role which holds the power to define and create different classes of women.
      Moreover, discourses of 'medical indication' and the 'best interests of children'
      intersect to inscribe a form of discursive eugenic practice which in turn
      sustains sexism and discrimination against childless women. Finally, this paper
      seeks to alert the nursing profession to requirements emerging from social policy
      which influence practice, interfere in client-nurse relationships, and may
      ultimately result in unethical conduct.

PMID- 9919104
TI  - Sharing in nursing governance: creating opportunities for change.
AB  - Shared governance has created a radical shift in the management and systems
      thinking of organisations by empowering employees through increased
      accountability, ownership and decision making. This paper outlines the process of
      introducing the concept of shared governance to the nursing division of a large
      not-for-profit private hospital in Victoria. The objectives for change and the
      philosophy of shared governance are explained so as to clarify the reasons for
      selection of the shared governance model. The steps involved in planning for the
      introduction of the change process, implementation and integration of the model
      at both organisational departmental levels, and the actual structure of the
      working model of shared governance are described.

PMID- 9919105
TI  - Measles (rubeola) virus.

PMID- 9919106
TI  - Web-site review: evidenced based practice.

PMID- 9919107
TI  - Marie Curie Cancer Care.

PMID- 9919108
TI  - Anxiety and the adult cancer patient.
AB  - While anxiety is a common psychological symptom in cancer patients,
      unfortunately, few patients are diagnosed or even treated for the symptoms that
      can occur due to the debilitating nature of anxiety. These can even lead to
      patients not following the best medical care to ensure they have the fullest
      chance of recovery. The following article discusses some of the anxiety related
      problems health care workers see in patients with cancer, and suggests ways to
      identify and treat patients with these anxiety disorders.

PMID- 9919109
TI  - Providing psycho-social support by telephone: what is its potential in cancer
      patients?
AB  - This paper provides an overview of the use of supportive telephone interventions
      in cancer patients. The small number of studies that have been reported to date
      have demonstrated that such approaches are feasible and well accepted. Current
      telephone counselling programmes for cancer patients have utilized both one-to
      one and group approaches. Given the promise of telephone interventions to provide
      assistance to patients who may not otherwise receive psycho-social care because
      of factors such as geographical isolation, physical limitations, or lack of
      comfort with face-to-face approaches, further development and evaluation of
      programmes in this area is critically needed. We identify priorities for future
      research, including determining the most effective ways to deliver telephone
      interventions, identifying patient groups in which they are most successful, and
      evaluating cost-effectiveness.

PMID- 9919110
TI  - The prevalence and detection of psychiatric morbidity in patients with metastatic
      breast cancer.
AB  - This study monitored the prevalence and detection of psychiatric morbidity in 80
      women newly diagnosed with metastatic breast cancer from diagnosis of metastatic
      disease over a 16-month period. Patients were interviewed at home every 8 weeks
      using the Hospital Anxiety and Depression Scale (HADS) and an interview schedule
      compiled by the author to monitor contact with members of the multidisciplinary
      team, demographic details, current treatment and sites of metastatic spread. One
      way analysis of variance (ANOVA) comparing the mean anxiety and depression scores
      at each interview demonstrated that there were no statistically significant
      differences in mood across the eight interviews, though there was a trend over
      the course of the eight interviews for mean anxiety and depression to decrease.
      Using the cut off scores suggested by the authors of the HADS, the scores were
      then categorized into case, borderline and normal. These analyses illustrated the
      relatively large proportion of patients who fell into the borderline and case
      ranges for anxiety and/or depression with, for example, 39% of women scoring in
      the case range for anxiety and 31% for depression at diagnosis of metastatic
      breast cancer. Detection of these mood problems was extremely low with referral
      to appropriate services not in evidence. The results of this study are consistent
      with those of other studies monitoring the psychological needs of women with
      breast cancer and the detection of mood disturbance. The clinical relevance of
      the results of the present study are discussed and future research avenues
      suggested.

PMID- 9919111
TI  - Epidemiology of prostate cancer in two European countries: Scotland and Norway.
AB  - The incidence of prostate cancer varies enormously throughout the world. Scotland
      and Norway are two European countries with similar populations, yet the incidence
      of prostate cancer in Norway is much greater than in Scotland. The aetiology and
      epidemiology of prostate cancer in both countries is discussed. Reference is made
      to age, socio-economic status, diet, hormones, genetic factors and vasectomy.

PMID- 9919112
TI  - Research with families in palliative care: conceptual and methodological
      challenges.
AB  - Conducting research with families of individuals receiving palliative care is
      challenging. Issues contributing to the challenge include defining the family,
      determining the unit of analysis in the level of inquiry, and identifying
      pathways to knowledge about the family. The purpose of this paper is to provide
      an overview of the major conceptual and methodological issues facing family
      researchers in general, with an aim to examining how these issues impact
      researchers studying families of individuals receiving palliative care.

PMID- 9919113
TI  - Characteristics of new referrals to twenty-seven lymphoedema treatment units.
AB  - Lymphoedema affects 25-28% of patients who have undergone axillary surgery or
      radiotherapy in the treatment of cancer. The prevalence of primary lymphoedema or
      of lymphoedema secondary to non-cancer causes is unknown. In addition, basic
      demographic and disease characteristics of the lymphoedema population remain
      undocumented. We conducted a prospective survey to determine these
      characteristics. Lymphoedema treatment clinics in the UK were invited to
      participate at the British Lymphology Society 1996 Annual Conference. Twenty
      seven clinics collected a standard data set for all new referrals in a 3-month
      period in 1997. The sample size was 603. The mean number of new referrals was 7.4
      patients per unit per month. Eighty per cent of patients had cancer-related
      lymphoedema, and 86% of patients were female. Patients' mean age was 61.0 years.
      Thirty-seven per cent of the sample had suffered lymphoedema for less than 3
      months, and 15% for 5 years or more. Patients with non-cancer related oedema had
      suffered the condition disproportionately longer than the cancer-related group
      (chi 2 = 102.2, P < 0.001). Sixty-six per cent of patients were reported as
      having lymphoedema at more than one site. Seventy-four per cent of all patients
      suffered unilateral limb oedema, and 23% bilateral limb oedema. Bilateral
      swelling was recorded for 67% of the non-cancer related group and 13% of the
      cancer related group (chi 2 = 153.4, P < 0.001). Median percentage excess volume
      (PCEV) for all patients with unilateral limb oedema was 16.4%. There was a
      positive relationship between PCEV and duration of the condition (H = 24.0, P <
      0.001), and PCEV and non-cancer related lymphoedema (H = 10.5, P < 0.05). These
      results suggest that patients with non-cancer related lymphoedema and those with
      cancer-related lymphoedema form two distinct groups. The former present
      substantial management problems which are made more complex by late referral.

PMID- 9919114
TI  - Everyday ethics.

PMID- 9919115
TI  - The public and private problem of euthanasia. A comparison of The Netherlands and
      the United States.
AB  - Euthanasia is an emerging public problem. The recent "medicalization" of the
      dying process in industrialized nations has engendered a fear of a painful and
      undignified death and the loss of control over one's final days. For people who
      live in societies with advanced medical resources and technology, euthanasia
      seems the only sure way to have "a good death." This article examines the public
      and private faces of euthanasia and provides another moral lens through which to
      view the issue. The article includes an interview with the son of a 78-year-old
      man who had active euthanasia performed by a family physician in the Netherlands.

PMID- 9919116
TI  - Nursing home resuscitation policies and practices for residents without DNR
      orders.
AB  - The purpose of this study was to explore the policies and practices of nursing
      homes with respect to the resuscitation of residents who do not have a do-not
      resuscitate (DNR) order. Responses from a survey of 36 facilities revealed that
      most residents had DNR orders and most facilities were capable of providing basic
      cardiopulmonary resuscitation (CPR). Less than 30% had performed CPR in the past
      6 months, and 22.8% had no written CPR policies. More facilities required CPR in
      witnessed arrests of non-DNR residents (79.3%) than in unwitnessed arrests (24%).
      Methods for identifying CPR status need improvement to enable accurate
      identification and prompt resuscitation of residents who want CPR.

PMID- 9919118
TI  - Continuity of care: a nursing needs assessment instrument.
AB  - Based on testing of the Uniform Needs Assessment Instrument (UNAI), a nursing
      needs assessment tool for adult hospitalized patients was integrated into nursing
      practice. Some content and format changes to the UNAI occurred as a result of the
      research process. The revised assessment form is called the Nursing Needs
      Assessment Instrument (NNAI). Community providers, including nursing home and
      home health care personnel, use the NNAI to derive necessary admission data for
      assessing patients, planning care, and communicating with other staff regarding
      patient needs. Instituting an evidence-based practice change in hospital
      discharge forms enables the next care provider to consistently meet the patient's
      continuing needs.

PMID- 9919117
TI  - Individualized assessment and intervention in bilateral siderail use.
AB  - The use of bilateral siderails, similar to physical restraints, can be safely
      reduced by a comprehensive assessment process. This article presents an
      individualized assessment for evaluating siderail use to guide nurses in managing
      resident characteristics for falling out of bed and intervening for high-risk
      residents. The individualized assessment is consistent with federal resident
      assessment instrument requirements and includes risk factors specific to falls
      from bed.

PMID- 9919119
TI  - Temporal arteritis.

PMID- 9919120
TI  - An interdisciplinary approach to urinary incontinence.
AB  - Preparatory to a survey by the Joint Commission on Accreditation of Healthcare
      Organizations, a skilled nursing facility identified a problem with patients who
      were incontinent and implemented an interdisciplinary practice change described
      in some detail. Additionally, this practice change was awarded the Innovations in
      Practice Award by the National Gerontological Nursing Association in 1996.

PMID- 9919121
TI  - Mary Lund, RN, PhD, nurse ethicist.

PMID- 9919123
TI  - Ethics in home health: dollars for care.

PMID- 9919122
TI  - Ethical issues concerning clinical trials.

PMID- 9919124
TI  - A quest for certified ophthalmic assistants.

PMID- 9919125
TI  - Macular hole surgery: helpful tips for preoperative planning and postoperative
      face-down positioning.
AB  - This discussion summarizes recommendations designed to assist the patient
      undergoing macular hole surgery in which a long-acting intraocular gas is used.
      These recommendations include suggestions for the patient's preoperative
      planning, postoperative expectations, face-down positioning, and recommended
      activities. Specific recommendations to help the patient more comfortably comply
      with the awkward positioning required for successful macular hole closure are
      included.

PMID- 9919126
TI  - Nystagmus: questions and answers.

PMID- 9919127
TI  - Cracking the crock: how to deal with factitious eye disease.

PMID- 9919128
TI  - An eye on wellness: focus on preventing disease.

PMID- 9919129
TI  - A 71-year-old blue-eyed woman present for evaluation of decreased vision. Ocular
      hemosiderosis.

PMID- 9919130
TI  - Managing decentration in rigid lens wearers.

PMID- 9919131
TI  - What, me exercise?

PMID- 9919132
TI  - Preoperative assessment criteria and patient teaching for ambulatory surgery
      patients.
AB  - Today's trend is to have the surgical patient return to the comfort of his or her
      home rather than be admitted to the hospital for expensive nursing and medical
      care. The perioperative team must initially assess the patient's American Society
      of Anesthesiology status, anxiety level, food and drugs to which he or she may be
      allergic, and skin integrity; obtain a medical and surgical history and consent;
      review laboratory, electrocardiogram, and radiological results; and perform
      preoperative teaching (e.g., which medications to take or withhold
      preoperatively, when to withhold food and fluids) and postoperative teaching
      (e.g., catheter care, dressing changes). In addition, the nurse needs to
      anticipate and be prepared for medical emergencies such as airway management
      problems and malignant hyperthermia. The age of the patient (e.g., pediatric and
      geriatric age groups) and preoperative disease states and their severity also
      need to be recognized as they impact on the perioperative outcome. The assessment
      phase is one of the most important phases in the perioperative experience. Proper
      evaluation is the key to success for positive surgical outcomes. Given the time
      constraints in the ambulatory surgical setting, assessing and teaching the
      patient on the day of surgery is not feasible or appropriate. Reaching out to the
      patient a few days before surgery either in the patient's home, in the ambulatory
      surgery center, or by telephone is the ultimate goal.

PMID- 9919134
TI  - Are you being sabotaged by your coworkers?
AB  - Men and women are both guilty of sabotaging coworkers, but men and women do it
      differently and for different reasons. Men tend to do it more overtly and for
      more work-related reasons. However, women are more covert; their reasons are
      motivated more by jealousy of another's success or their own insecurity. Once
      women are betrayed by another, they take it more personally than their male
      counterparts. Men confront the betrayer and move on; that is business. Women do
      not confront the betrayer and see betrayal in the workplace as being let down by
      their friends. Women need to treat business relationships and situations as
      business, not as friendships.

PMID- 9919133
TI  - Constant temperature monitoring: a study of temperature patterns in the
      postanesthesia care unit.
AB  - Patients admitted to the PACU from the operating room exhibit fluctuations in
      core body temperature during the course of their stay in the PACU. Some patients
      present with normothermia and experience temperature decreases later in their
      stay. PACU policy does not dictate that temperatures be measured at a
      predetermined frequency in the absence of hypothermia; thus, it is possible that
      hypothermia may not be detected at its onset. The major purpose of this study was
      to describe the core body temperature patterns of postsurgical patients during
      the PACU stay. Secondary objectives were to (1) identify at which point in time
      patients become hypothermic and (2) describe length of stay in patients who
      develop hypothermia. Hypothermia was defined as a core tympanic temperature of
      less than 35.5 degrees C. A descriptive design was used using a convenience
      sample of 150 elective surgical patients over the age of 1 month who were
      normothermic on admission to the PACU. Data were analyzed using descriptive
      statistics. Concurrent tympanic and continuous axillary temperatures were
      monitored for comparison and trend monitoring. Temperatures showed clinically
      significant decreases into the hypothermic range (< 35.5 degrees C). Fifty-seven
      percent of the sample (n = 86) had temperatures that dropped after PACU admission
      and another 13% fell below 35.5 degrees C. Hypothermia occurred within the first
      15 minutes of the PACU stay. The average length of stay for those that developed
      hypothermia was 1.83 hours. Monitoring temperatures more frequently will result
      in detecting hypothermia at its onset. Nurses may use the axillary device as a
      trend for continuous monitoring. Length of stay may be shortened if temperature
      management is embraced by the PACU nurse.

PMID- 9919135
TI  - Malignant hyperthermia: considerations for ambulatory surgery.
AB  - Patient care offered on an ambulatory basis continues to grow as evidenced by the
      high percentage of surgical procedures now being performed in such a setting.
      Many ambulatory surgical facilities are free standing and remote from the primary
      hospital location. As the popularity of ambulatory surgical care increases, so
      does the likelihood of encountering malignant hyperthermia-susceptible patients
      or of experiencing a malignant hyperthermia crisis. The management of this unique
      population creates new challenges for the perianesthetic nurse working in the
      free-standing ambulatory setting. A comprehensive plan of patient care under
      these circumstances includes (1) the ability to identify the high-risk patient
      and to plan their care accordingly, (2) early recognition of the signs and
      symptoms of malignant hyperthermia, and (3) being prepared to promptly and
      efficiently treat a malignant hyperthermic event. This review article will offer
      guidelines for managing the malignant hyperthermia-susceptible patient in the
      remote ambulatory surgical setting.

PMID- 9919136
TI  - Practical points for the patient with preexisting renal disease.
AB  - The third in a series, it is the purpose of this article to discuss common
      preexisting renal diseases seen in patients presenting for surgery. Defining
      characteristics, the pathophysiology of each disease, its causes, and treatments
      are presented along with perioperative nursing implications.

PMID- 9919137
TI  - Being the boss is not what it used to be!
AB  - Mentoring has a long and varied history. It was a method for helping people grow
      to competence in a supportive environment. As being a boss continues to have less
      and less real power associated with the role, the idea of approaching employees
      as partners in getting the work accomplished makes the concept of mentoring
      applicable to today's workplace and today's workforce.

PMID- 9919138
TI  - Reimbursement for WOC (ET) nurse services in the long-term care setting.

PMID- 9919139
TI  - President's message: end-of-life care.

PMID- 9919140
TI  - A report card on wound care research: support surface issues and beyond.

PMID- 9919141
TI  - The changing face of continence nursing.

PMID- 9919142
TI  - Nursing assessment: impact on type and cost of interventions to prevent pressure
      ulcers.
AB  - OBJECTIVE: To describe pressure ulcer preventive interventions and their cost,
      and to compare the preventive intervention use and cost with level of risk.
      DESIGN: Comparative, descriptive design. SETTING AND SUBJECTS: A large midwestern
      Veteran's Affairs Medical Center with 260 long-term care beds. Thirty-one chair-
      or bed-bound residents from 1 long-term care unit comprised the study sample.
      MAIN OUTCOME MEASURES: The outcome variables included demographic information
      (patient record), Braden Risk Assessment score, institutional risk assessment
      score (Pressure Ulcer Risk Tool), type and frequency of preventive interventions,
      and the related costs. METHODS: Subjects were assessed on a weekly basis for type
      and frequency of preventive intervention and for the development of a pressure
      ulcer. Each subject was observed until death, discharge, pressure ulcer
      formation, or the end of the 3-month study period. RESULTS: The 3-month pressure
      ulcer incidence rate was 13%. All subjects were at risk for pressure ulcer
      development according to Braden scores; whereas only 74% were assessed at risk
      with use of the facility's risk assessment tool. Preventive measures included
      regular repositioning (87%); 67% were placed on mattress support surfaces. There
      was no relationship between level of risk (facility risk tool score) and type of
      prevention used. The total cost of pressure ulcer prevention to the nursing unit
      was $14,926, representing a mean of $497 per subject, and $5.55 per subject per
      day. CONCLUSION: As compared with previous studies, the higher cost of prevention
      described in this study may be attributed to inadequate linkage of preventive
      interventions to risk level.

PMID- 9919143
TI  - Use of vacuum-assisted wound closure in three chronic wounds.
AB  - Vacuum-assisted wound closure has been reported to promote the healing of chronic
      wounds by increasing the vascularity and oxygenation of the wound bed,
      maintaining a moist environment, and removing exudate through negative pressure.
      The results of vacuum-assisted wound closure for 3 patients with chronic wounds
      are presented.

PMID- 9919144
TI  - Electric stimulation and wound healing.
AB  - Interest in accelerating the process of wound healing has existed since the
      beginning of health care. Although significant advances have been made in our
      understanding of the stages of wound healing, the mediators of tissue repair and
      regeneration, as well as the efficacy of many treatments, have not been fully
      evaluated. This article will review electric stimulation as one means to promote
      wound healing.

PMID- 9919145
TI  - Response to urinary incontinence by older persons living in the community.
AB  - PURPOSE: To investigate the responses to urinary incontinence (UI) of older
      persons living in the community. DESIGN: Detailed interviews were completed on a
      sample of 42 independent, community-dwelling persons who were at least 60 years
      of age. Nineteen participants reported UI, and their experiences are reported in
      detail. SETTING AND SUBJECTS: Subjects were recruited from 3 sources: volunteers
      who acknowledged having UI, those with known UI who were invited by their doctors
      to participate, and those who selected "Loss of bladder control" in a 20-card
      sort of common ailments. All interviews were conducted in a private setting at a
      seniors center or at participants' church or home. INSTRUMENTS: Twenty cards with
      a common ailment printed in large type and an interview schedule with questions
      relating to the ailment selected as having the most impact were used; demographic
      data were collected on a standardized form. METHODS: Interviews were recorded on
      audiotape and lasted from 20 to 60 minutes. These recordings were analyzed for
      themes with use of Ethnography software. MAIN OUTCOME MEASURES: Demographic and
      other data from the interview schedule were tabulated. The communication style of
      the 19 subjects with UI was analyzed to determine how freely they spoke about
      problems with bladder control to family and friends and their sources of
      information for managing urinary leakage. Analysis was done both by the
      researcher and a faculty member; an interrater reliability of 1.00 was achieved.
      RESULTS: There was little difference in the self-rating of health for those with
      or without UI. Subjects recruited by letters sent to doctors' patients ranked the
      impact of loss of bladder control higher than other subjects did. Of the 19
      subjects with UI, 10 spoke freely to family and friends, but 9 seldom discussed
      the subject--and then only to a family member. Four of the 9 with a closed
      communication style reported no current source of information about UI or its
      management. CONCLUSION: Though UI had a major effect on the lives of these
      subjects, they were more willing to admit having "loss of bladder control" than
      "urinary incontinence." Communication style is related to prior sources of
      information about UI, but not its perceived impact on health. This relationship
      helps to determine the teaching methods that are most likely to influence elderly
      persons with UI who have either on open or closed communication style.

PMID- 9919146
TI  - Toilet tales: stool toileting refusal, encopresis, and fecal incontinence.
AB  - Defecation difficulties in children present as stool toileting refusal,
      encopresis (caused by idiopathic or functional constipation), or fecal
      incontinence (caused by anatomic or neurologic disorders). The appropriate
      evaluation, treatment, and expected treatment results for children with stool
      soiling are presented.

PMID- 9919147
TI  - Skin and wound care management for a child with epidermolysis bullosa.

PMID- 9919172
TI  - Care is not compromised.

PMID- 9919173
TI  - Ring of confidence.

PMID- 9919174
TI  - The public says pay up.

PMID- 9919175
TI  - Fashionable genes.

PMID- 9919176
TI  - All clear.

PMID- 9919177
TI  - Two sides of a coin.

PMID- 9919179
TI  - Back to basics.

PMID- 9919178
TI  - Snapshot survey.

PMID- 9919180
TI  - Nurse 98 awards. A touching story. Interview by Anna Minton.

PMID- 9919181
TI  - Sheathed in history.

PMID- 9919182
TI  - Once bitten.

PMID- 9919183
TI  - Disappearing nurses.

PMID- 9919184
TI  - Aromatherapy in arthritis: a study.
AB  - In an attempt to redress the lack of research into the use of complementary
      therapy in the nursing care of patients with rheumatoid arthritis, the author
      studied the effects of massage and aromatherapy on patients' wellbeing.

PMID- 9919185
TI  - Using telematics with older people: the ACTION project. Assisting Carers using
      Telematics Interventions to meet Older persons' Needs.
AB  - In this article, the authors provide an overview of the pan-European Assisting
      Carers using Telematics Interventions to meet Older persons' Needs (ACTION)
      project. They focus on the developmental aspects of the ACTION project and
      discuss ongoing work and future development plans.

PMID- 9919186
TI  - Infertility treatment in women aged over 40 years.
AB  - The question of whether women over 40 years should be accepted for fertility
      treatment poses ethical and moral dilemmas for doctors, nurses and midwives. This
      article examines the issues involved in infertility management and care of older
      women.

PMID- 9919187
TI  - Facilitating return to practice.
AB  - The government has recently announced its intention to recruit nurses back into
      the profession. In this article, the authors describe an initiative undertaken by
      their trust to facilitate return to practice programmes, outlining the programme
      objectives and outcomes to date.

PMID- 9919188
TI  - Meningococcal disease.
AB  - This article discusses meningococcal disease and outlines the role of the nurse
      in treating patients who may suffer from meningitis, one of the illnesses caused
      by meningococcal disease. It goes on to discuss how nurses can support the
      relatives of these patients.

PMID- 9919189
TI  - The concept of magnet hospitals.

PMID- 9919191
TI  - Lessons to be learned.

PMID- 9919192
TI  - Writing a new script.

PMID- 9919190
TI  - Show us the money.

PMID- 9919193
TI  - Life decisions.

PMID- 9919194
TI  - Meeting point.

PMID- 9919195
TI  - Nurse 98 awards. Making dreams come true. Interview by Charlotte Alderman.

PMID- 9919197
TI  - Powerful nurses protecting patients. Interview by Ruth Lancaster.

PMID- 9919196
TI  - A new life. Interview by Mary Hampshire.

PMID- 9919198
TI  - Developing management skills.
AB  - Nurse leaders in Wales, with the support of chief executives and the Welsh Office
      are taking control of nurse development. Georgina Gordon explains how.

PMID- 9919199
TI  - HIV-related encephalopathy.
AB  - This article discusses different models of care in the UK for the small number of
      patients with HIV-related encephalopathy. A combination of intensive community
      support, residential care and respite care has been shown to be more effective
      than hospital care. The authors emphasise the importance of early
      neuropsychological assessment, the provision of a broad range of services with an
      appropriate skill mix of carers and the need for staff education and support.

PMID- 9919200
TI  - Academic accreditation.
AB  - If you are planning to take a course at a higher education institution, you may
      be able to claim academic credit for learning from experience. Some people are
      put off by the complexities of the application process. This encouraging article
      discusses the principles of learning from experience, and offers a step-by-step
      guide to gaining academic accreditation for experiential learning.

PMID- 9919201
TI  - Next of kin.
AB  - Who exactly is a patient's 'next of kin' and why do nurses need to know? Does the
      term include partners--including same sex partners--who are not related by blood
      or marriage? Drawing on the negative experiences of lesbians and gay men, this
      article offers guidance on these difficult questions and recommends that
      admission documents be changed to reflect the patient's wishes.

PMID- 9919202
TI  - Controlling breakthrough pain in palliative care.
AB  - This article challenges the common practice of boosting the syringe driver as a
      means of controlling breakthrough pain. The authors offer some guidelines for
      good practice for managing the MS26 syringe driver when used for pain control.

PMID- 9919204
TI  - How managers feel about nurses.

PMID- 9919203
TI  - Oxygen therapy.
AB  - This article aims to give a general overview of oxygen therapy, both in the short
      and long term. Various methods of oxygen delivery and storage are discussed,
      along with the nurse's role in caring for a patient receiving oxygen therapy.

PMID- 9919205
TI  - Helping nurses to look after themselves. Interview by Katherine Burke.

PMID- 9919206
TI  - Fighting for fair play. Interview by Sharon Watson.

PMID- 9919207
TI  - Breaking the bars to prison health care.

PMID- 9919208
TI  - Record time.

PMID- 9919210
TI  - Independence day.

PMID- 9919209
TI  - Schools out.

PMID- 9919211
TI  - Career pathways.

PMID- 9919212
TI  - Swaziland--will nurses carry guns for protection?

PMID- 9919213
TI  - As seen on TV. Interview by Charlotte Alderman.

PMID- 9919214
TI  - The language of care. Interview by Jo Carlowe.

PMID- 9919215
TI  - The ICN website offers a global view.

PMID- 9919216
TI  - Skin care.
AB  - Proposals from an All Parliamentary Group on Skin could improve the way the NHS
      manages skin disease. Many skin disorders could be managed in primary care,
      freeing up valuable specialist expertise for more serious cases.

PMID- 9919217
TI  - Mental health facilitators in primary care.
AB  - In the context of the National Primary Care Facilitation Programme, the Sainsbury
      Centre for Mental Health has reviewed the membership of the Mental Health in
      Primary Care Network, and explored members' roles; the findings of the review are
      reported in this article. Researchers examined the activities undertaken by
      network members, and identified the proportion working directly with primary
      health care teams and those working strategically within health authorities.
      Education and training, health promotion, and liaison and linkworking were
      undertaken by many staff, while a few worked at a more strategic level. In order
      to increase the effectiveness of this model, a more focused approach is
      recommended, targeting those with responsibility for implementing changes and
      developing mental health care in primary care settings. Learning sets which
      involve primary care and mental health teams, and strategic work with health
      authorities, are also recommended.

PMID- 9919218
TI  - Patients' rights to access their healthcare records.
AB  - Improving communication between different healthcare disciplines and with
      patients is hampered by professional insecurity. In this article, the authors
      examine the compelling reasons for making records more accessible to patients and
      describe the potential benefits for patients and professionals.

PMID- 9919219
TI  - Alcohol education in primary schools.
AB  - Educating teenagers about the risks of alcohol may be too late--many 12- and 13
      year-olds have already started experimenting with it, and face increasing peer
      pressure to take risks. This article describes how a community alcohol team
      developed a programme for primary school alcohol education. The team believes
      that if healthy attitudes are established sufficiently early, the risks will be
      reduced, and harm-free drinking patterns will develop more quickly.

PMID- 9919220
TI  - Training-needs analysis.
AB  - This article introduces training-needs analysis (TNA) and places the process in
      the broad context of a training strategy. It aims to inform nurses on how the
      principles of TNA can be applied to their own practice.

PMID- 9919221
TI  - Better pay for nurses.

PMID- 9919222
TI  - Nurses not invited.

PMID- 9919223
TI  - Quality time.

PMID- 9919224
TI  - A small risk is too much.

PMID- 9919225
TI  - Don't blame agencies.

PMID- 9919226
TI  - Cruel and pointless.

PMID- 9919227
TI  - Disabling discrimination.

PMID- 9919228
TI  - Savage culture.

PMID- 9919229
TI  - Impact of a death.

PMID- 9919230
TI  - What's in a name?

PMID- 9919231
TI  - On the home straight.

PMID- 9919232
TI  - Nurse 98 awards. Creative work. Interview by Charlotte Alderman.

PMID- 9919233
TI  - Must do better.

PMID- 9919234
TI  - Organ donation.
AB  - A publicity campaign to increase the supply of donor organs has been run recently
      by the Department of Health to persuade potential donors to let those closest to
      them know that they want to donate their organs when they die. The campaign has
      no time limit, unlike those people needing donated organs.

PMID- 9919236
TI  - Nursing knowledge: the role of Plato in wound care.
AB  - Using wound care as an example, the author reflects on the knowledge and skills
      practised by nurses in nursing and research. He emphasises reflecting on
      practice, and introduces the importance of non-existent states of affairs, the
      grasp of which is essential in analysing what it is to act in patients' best
      interests.

PMID- 9919235
TI  - Nursing mathematics: the importance of application.
AB  - This study explores the effectiveness of a revision programme in nursing
      mathematics for student nurses. Students who took the revision programme achieved
      a marked improvement in test results, although some still scored low in written
      tests. When interviewed, the students reported that they had difficulty applying
      written work in the classroom to actual calculations in the workplace. They found
      that only by 'doing' mathematics did the theory make sense. The author recommends
      that students should be encouraged to maximise the opportunities to practise
      mathematics in the clinical setting.

PMID- 9919237
TI  - Challenging behaviour in HIV services.
AB  - 'Challenging behaviour' is a label, and one that is often misused in the context
      of mental health. Using a profile, this article identifies a number of behaviours
      that may challenge service. Peter has HIV and has developed a related
      opportunistic illness, affecting brain function. The author stresses the
      importance of person-centred care, urging providers to audit their services and
      evaluate the requirement for alterations to assessment documentation to meet the
      changing needs of individuals, families and children living with HIV/AIDS.

PMID- 9919238
TI  - Constipation.
AB  - Although rarely life threatening, constipation can be the cause of misery and
      discomfort for people suffering from it. Jane Winney shows how appropriate
      assessment and an understanding of bowel function can help its elimination.

PMID- 9919239
TI  - Injection technique intramuscular--2.

PMID- 9919240
TI  - A campaign to stamp out violence.

PMID- 9919241
TI  - Burden of proof. Interview by Frank Chalmers.

PMID- 9919242
TI  - Can these people be helped?

PMID- 9919243
TI  - A fly on the wards.

PMID- 9919244
TI  - Safety in numbers.

PMID- 9919245
TI  - The end of nursing as we know it.

PMID- 9919246
TI  - Understanding depression.

PMID- 9919247
TI  - Live through this.

PMID- 9919248
TI  - What's so good about natural pain?

PMID- 9919249
TI  - The light fantastic.

PMID- 9919250
TI  - Cardiac rehabilitation. Gym will fix it.

PMID- 9919251
TI  - Edna's war.

PMID- 9919252
TI  - Modesty blaze.

PMID- 9919253
TI  - The Tex-Mex leap.

PMID- 9919254
TI  - Fiesta of death.

PMID- 9919255
TI  - Face to face.

PMID- 9919256
TI  - Using an interactive video disk in breast cancer patient support.
AB  - A randomised-controlled trial compared outcomes for women recently diagnosed with
      breast cancer who either received support and information from a
      multidisciplinary team or used a shared decision-making programme on an
      interactive video disk (IVD) system. Using the IVD did not have a significant
      effect on the decisions women made about treatment, yet it was evaluated
      positively by those who used it. The results suggest that the role of clinical
      staff is more significant than the form of information provided. Potential
      benefits for the IVD were apparent such as standardising the information received
      by patients, promoting evidence-based practice and providing a measure for
      quality assurance.

PMID- 9919257
TI  - Loss of body heat following surgical intervention.

PMID- 9919258
TI  - Hepatitis: symptoms, treatment and prevention.

PMID- 9919260
TI  - Restraint and sudden death from asphyxia.

PMID- 9919259
TI  - A role change for auxiliaries.
AB  - Development of a practice-based, self-contained community nursing team prompted
      consideration of how best to make use of available skill mix. This article
      describes an initiative involving training of the nursing auxiliary in the team
      to offer venepuncture to housebound patients.

PMID- 9919261
TI  - Latex allergy: reducing the risks.

PMID- 9919262
TI  - Public relations.

PMID- 9919263
TI  - Containment areas.

PMID- 9919264
TI  - Ladies at war.

PMID- 9919265
TI  - Book of memories.

PMID- 9919266
TI  - More than 80 years after the Battle of the Somme.

PMID- 9919267
TI  - Behind closed doors.

PMID- 9919269
TI  - Time to fight.

PMID- 9919268
TI  - Purchasing power.

PMID- 9919270
TI  - Nurses, nurses everywhere.

PMID- 9919271
TI  - The young ones: teenagers in hospital.

PMID- 9919272
TI  - The emotional road to recovery.

PMID- 9919274
TI  - Teenagers need to be given special attention.

PMID- 9919273
TI  - Dangerous liaison.

PMID- 9919275
TI  - NT/3M National Nursing Awards. A winning combination.

PMID- 9919277
TI  - So you think you've got it tough?

PMID- 9919276
TI  - Yellow letter day.

PMID- 9919278
TI  - Homeless where the heart is.

PMID- 9919279
TI  - When management skills are taught instead of basic nursing techniques.

PMID- 9919281
TI  - Learning disabilities in later life.

PMID- 9919280
TI  - Nurse-led diabetes clinics benefit black and Asian patients.
AB  - There is strong epidemiological data that shows that prevalence of diabetes
      varies with ethnic origin. This article describes the establishment of diabetic
      clinics within general practices in an attempt to identify and meet the needs of
      minority ethnic groups in relation to this condition. A future article will
      describe opportunistic screening of the target population.

PMID- 9919282
TI  - Sexual parasites.

PMID- 9919283
TI  - Elder abuse: issues for nurses.

PMID- 9919284
TI  - Skills needed in caring for people with dementia.

PMID- 9919285
TI  - Nurse to patient ratios and patient outcomes.
AB  - The findings of this study suggest that currently available data could be used to
      monitor changes and trends in nurse to patient ratios. A link was discovered
      between nurse staffing levels and patient readmission rates that has not been
      addressed in the literature, although this would require further investigation.

PMID- 9919286
TI  - Ancient and modern: the best of both.

PMID- 9919287
TI  - Moist wound healing: the evidence.

PMID- 9919288
TI  - Taking the pressure off.

PMID- 9919289
TI  - In search of a sound knowledge base.

PMID- 9919291
TI  - The Y2K bug: will it sting healthcare?

PMID- 9919290
TI  - How a short stretch can work wonders.

PMID- 9919292
TI  - Truth telling.
AB  - Truth telling is considered a respected and honored tradition in American
      culture. This paper discusses truth telling within the context of healthcare,
      including the duty to tell the truth, the nature of truth telling, and common
      practices for avoiding the truth. Ethical considerations are reviewed within the
      context of truth telling, and a case study is presented.

PMID- 9919293
TI  - Managing wounds in a managed care environment: the integration concept.
AB  - Integration is being discussed at all levels today in healthcare. The term is
      confusing and the literature provides numerous definitions and explanations. In
      general, integration refers to the coordination and reorganization of various
      healthcare units (such as home health care, acute care hospitals, and skilled
      nursing facilities) either horizontally, vertically, or via a combination of
      both. To discuss integration, a healthy understanding of managed care and
      healthcare trends are essential. With current and projected future trends serving
      as a backdrop, this article will attempt to describe various integration delivery
      models. The application of the above to wound care as a specific disease state
      serves as the closing message.

PMID- 9919294
TI  - MDS+ RAP items associated with pressure ulcer prevalence in newly
      institutionalized elderly: study I.
AB  - All federally funded facilities are required to use the Minimum Data Set Plus
      (MDS+) for functional assessment of their residents. Within the MDS+ there are 18
      specific conditions addressed through Resident Assessment Protocols (RAPs). There
      is a RAP for pressure ulcers but the validity of the pressure ulcer RAP items has
      not been documented. The purpose of this study was to determine which pressure
      ulcer RAP items correlate with pressure ulcer prevalence in newly
      institutionalized elderly and whether inclusion of nutritional status information
      to the correlated RAP items increases association with pressure ulcer prevalence.
      Data were collected through a retrospective chart review of 990 residents over
      age 65 at 8 nursing homes. Five pressure ulcer RAP items were predictive of
      pressure ulcer prevalence 19.76% of the time. When nutritional status markers
      were added in a logistic regression, pressure ulcers were correctly predicted
      32.3% of the time. In clinical practice, the pressure ulcer RAP needs to include
      nutritional status information to accurately reflect pressure ulcer risk.

PMID- 9919295
TI  - Pain associated with venous ulcers in injecting drug users.
AB  - Pain is a concern among people with venous ulcers. Although the prevalence is
      unknown, venous ulcers occur in those who have a history of illicit injecting
      drug use. The purpose of this study was to (a) examine the relationship between
      venous ulcer characteristics and pain severity, (b) ascertain factors that cause
      pain, (c) determine methods to alleviate pain, and (d) explore beliefs about pain
      medications among people with a history of injection drug use. Thirty-two
      patients answered pain and demographic questionnaires and had their venous ulcers
      traced onto plastic to identify wound area. Greater current pain, worse pain in
      24 hours, and higher levels of pain relief from medications were significantly
      related to larger wound areas. Ibuprofen, compression dressing Unna's boot, and
      heroin ranked highest in decreasing pain. The most painful activities were
      working, walking outside, standing, and stair climbing. Many patients (41%) did
      not like to bother others with their complaints of pain. Participants were
      generally satisfied with pain treatments and the response of care providers to
      their pain. People who have used injected drugs and have venous ulcers do have
      pain. Therefore, research must continue to evaluate this pain as well as the best
      ways to treat it.

PMID- 9919296
TI  - Nursing outcomes accountability. Moving to measurement.

PMID- 9919297
TI  - Linking outcomes management and practice improvement. The link between outcomes
      management and JCAHO functions.
AB  - Staff participating in the CABG outcomes management program continue to examine
      the effectiveness and efficiency of care processes and to redesign care to
      improve patient and organizational outcomes. In fact, this quality enhancement
      program is neverending as we strive continually to improve the care of CABG
      patients. The success, measured through improved process and outcome variables,
      has promoted the implementation of similar programs for other patient
      populations. Using foresight in the development of outcomes management programs
      to ensure inclusiveness of regulatory body or agency criteria encourages
      comprehensive programs that yield positive outcomes for both patients and
      organizations.

PMID- 9919303
TI  - Then and now.

PMID- 9919300
TI  - Evaluation of variances in patient outcomes.
AB  - New knowledge and understanding about improving the quality and reducing the
      costs of care will come from careful scrutiny of the variations in the outcomes
      of nursing interventions. Nurses need to systematically identify and measure
      outcomes, understanding the probabilistic nature of these patient responses to
      the care received. Using a formative evaluation process, nurses should measure
      degrees of patient outcomes over time to ascertain the effects of nursing care
      and analyze the variances in these observed outcomes from what was expected.
      Critical pathways are valuable tools for guiding evaluations of nursing care
      along a timeline and can lead to improvements in nursing care.

PMID- 9919302
TI  - Strategies to enhance internal validity in multi-center longitudinal research.
AB  - Lack of standardized data collection procedures in multi-center longitudinal
      research poses potential threats to the internal validity of the study. This
      article addresses several key issues in data collection that can affect the
      results of longitudinal research. The authors describe these issues in relation
      to the study currently in progress and cite specific strategies used during data
      collection to reduce or eliminate data collection inconsistencies. Use of these
      strategies is not limited to longitudinal, nonexperimental causal models.
      Outcomes managers and clinical nursing researchers may find some of the
      strategies useful to enhance the internal consistency of experimental and
      nonexperimental cross-sectional research.

PMID- 9919298
TI  - Utilizing collaborative practice to achieve quality outcomes in gentamicin
      administration.
AB  - An individualized weight-based gentamicin dosing program is used at this
      community hospital to achieve stable serum drug levels with optimal clinical
      outcomes. This program requires extensive communication between disciplines and
      because of its complexity, was identified by the nursing staff as being confusing
      to initiate and maintain. The authors report the work of an interdisciplinary
      team to streamline the ordering and administering process and to promote staff
      satisfaction in using the dosing program.

PMID- 9919301
TI  - Quantifying psychosocial nursing interventions provided to geropsychiatric
      inpatients.
AB  - The purpose of this pilot study was to develop and test the Geropsychiatric
      Intervention Checklist (GPIC), a measure designed to quantify psychosocial
      nursing interventions provided to persons on a geropsychiatric inpatient unit (N
      = 48). Data were collected by nursing staff, using self-report methods. This
      pilot study lays the foundation for future research designed to examine the
      impact of nursing interventions on geropsychiatric inpatient outcomes.

PMID- 9919304
TI  - Repolarization abnormalities in patients with idiopathic ventricular
      tachycardias.
AB  - STUDY POPULATION: Twenty patients without laboratory evidence of cardiac disease
      who underwent electrophysiological study because of recurrent ventricular
      tachyarrhythmias. PATIENTS AND METHODS: The study population was divided into two
      groups: group A (20 patients [six males and 14 females] mean age 42.2 +/- 13
      years), with idiopathic ventricular tachycardia (VT), and group B (30 controls
      [10 males and 20 females] mean age 43.6 +/- 16 years). Noninvasive
      multiparametric analysis of the ventricular repolarization phase was performed on
      the standard 12-lead electrocardiogram by using a digitizer connected with a
      computerized system. The intervals JT, heart rate-corrected JT (JTc), JT apex
      (JTa), heart rate-corrected JTa (JTac), T apex T end (TaTe) and heart rate
      corrected TaTe (TaTec) were measured and considered to be representative of the
      whole depolarization process. QT dispersions (QTeD) and QTc dispersions (QTecD)
      were calculated to assess the degree of spatial inhomogeneity of action potential
      duration. RESULTS: Patients in group A had higher JT (272 +/- 36 ms versus 265 +/
      25 ms, P = 0.01), JTc (336 +/- 28 ms versus 318 +/- 18 ms, P = 0.01), JTa (210
      +/- 28 ms versus 185 +/- 28 ms, P = 0.001) and JTac (240 +/- 20 ms versus 215 +/-
      13 ms, P < 0.001) values than those of patients in group B, despite shorter TaTe
      (71 +/- 10 ms versus 90 +/- 18 ms, P < 0.001) and TaTec (88 +/- 12 ms versus 110
      +/- 12 ms, P < 0.001). Moreover, QTeD and QTecD were significantly longer in
      group A than in group B (55 +/- 18 ms versus 42 +/- 19 ms [P = 0.01] and 80 +/-
      18 ms versus 55 +/- 28 ms [P = 0.001], respectively). CONCLUSIONS: Patients with
      idiopathic VT exhibit inhomogeneous prolongation of ventricular repolarization,
      due to a considerable increase in the initial part in association with a shorter
      terminal phase, as well as a greater dispersion of ventricular repolarization.

PMID- 9919305
TI  - Preliminary clinical experience with the pullback atherectomy catheter and the
      study of proliferation in coronary plaques.
AB  - BACKGROUND: Clues to the biology of coronary artery disease can be obtained
      through the study of proliferation in human coronary artery plaques. Previously,
      immunocytochemistry has been used to detect the proliferating cell nuclear
      antigen to demonstrate low levels of proliferation in directional coronary
      atherectomy tissue fragments resected from human coronary arteries. OBJECTIVES:
      To describe the proliferative profile of coronary artery tissue by using a more
      sensitive marker for cell replication. PATIENTS AND METHODS: Ten patients with
      unstable or stable angina pectoris underwent coronary atherectomy with a newer
      coronary atherectomy device, the Arrow-Fischell pullback atherectomy catheter.
      The histological features of the specimens were studied by using light
      microscopy, and cell proliferation was assessed with the use of in situ
      hybridization for the S phase-specific mRNA species, histone H3. RESULTS:
      Pullback coronary atherectomy immediately followed by percutaneous transluminal
      coronary angioplasty resulted in angiographic improvement in the lumen diameter
      in all but one patient, who required insertion of a stent. The atherectomy
      specimens consisted of a combination of atheromatous plaque and media. Four
      specimens had a small amount of adventitia. Five of the 10 specimens had no
      proliferating cells. Three specimens had between one and five proliferating cells
      per slide, while two specimens had relatively high proliferation indexes (2.5%
      and 4.2% of all cells per atherectomy cross-section). Both smooth muscle cells
      and macrophages were identified in areas with proliferating cells. The histology
      and proliferation profiles of the tissue resected from patients with stable and
      unstable angina were similar. CONCLUSIONS: Pullback atherectomy can be used
      effectively to debulk coronary artery lesions. By using a sensitive marker for
      cell replication, it was determined that the majority of the tissue specimens
      have low proliferation indexes.

PMID- 9919299
TI  - Utilization-focused evaluation of acute care nurse practitioner role.
AB  - Using nurse practitioners in acute care is a relatively new phenomenon with
      little existing data on related expectations and effectiveness. This article
      describes one organization's program evaluation of the Advanced Practice
      Registered Nurse (APRN) role. It includes a conceptual model as well as pragmatic
      data on: perception of the performance of agreed-upon role expectations,
      influence on targeted aspects of care, retention of a focus on nursing, and
      factors facilitating or hindering APRN effectiveness.

PMID- 9919306
TI  - Rapidly evolving constrictive tuberculous pericarditis: case presentation and
      review of the literature.
AB  - A 69-year-old male presented with a diagnosis of idiopathic pericarditis, first
      treated with prednisone for a few weeks with resolution of the symptoms. A few
      days after stopping the medication, he presented with malaise, cough and signs of
      pericardial constriction confirmed by echocardiography. He was diagnosed with
      pulmonary tuberculosis with pericardial involvement and treated accordingly.
      Pericardiectomy was performed after a few days of treatment because the symptoms
      related to constriction progressed. The procedure was successful, and the patient
      was completely asymptomatic after 10 months. The removed pericardium stained
      positive for acid-fast bacilli.

PMID- 9919307
TI  - A physician for the 21st century.

PMID- 9919308
TI  - Structural and functional analysis of the protein products derived from mutant
      fur alleles in an endoprotease-deficient Chinese hamster ovary cell strain.
AB  - The fur gene encodes the endoprotease, furin. We recently demonstrated mutations
      in both fur alleles in the mutant Chinese hamster ovary (CHO)-K1 strain, RPE.40,
      and hypothesized that these mutations were responsible for the endoprotease
      deficient phenotype of these cells. We now present the structural and functional
      properties of three protein products derived from the mutant fur alleles. None of
      these protein products were able to process the precursor to von Willebrand
      factor, which is processed by wild-type furin. Pro-protein processing activity
      initially attributed to one of the mutant proteins was due to wild-type furin
      produced inadvertently from one of the expression constructs used in these
      experiments. None of the mutant proteins exhibited evidence of autocatalysis,
      consistent with the lack of activity versus the test substrate, and glycosylation
      patterns suggested at least two of them remained in the endoplasmic reticulum.
      These results confirm that RPE.40 cells are furin null mutants, as earlier
      evidence had suggested.

PMID- 9919309
TI  - Targeted recombination at the Chinese hamster APRT locus using insertion versus
      replacement vectors.
AB  - In this study, we have examined the effects of targeting vector configuration and
      site of vector linearization on the frequency of targeted recombination at the
      endogenous CHO APRT locus, and have analyzed the types and class distributions of
      APRT+ recombinants obtained in APRT targeting experiments employing uncut
      circular, insertion-type (ends-in), and replacement-type (ends-out)
      configurations of the same pAG7 targeting vector, including configurations
      produced by introduction of a double-strand break (DSB) at sites either within,
      or at the 5' or 3' boundaries of APRT targeting homology. Our results suggest
      that: 1) plasmid-chromosome targeted recombination in mammalian cells may not be
      stimulated to the same degree by a DSB in the targeting vector as by a DSB in the
      chromosomal target; 2) recombinant class distributions are highly dependent upon
      targeting vector configuration; and 3) one-sided invasion mechanisms may play a
      significant role in homologous recombination in mammalian cells.

PMID- 9919310
TI  - Genetic variation in the 3' untranslated region of the neurofibromatosis 1 gene:
      application to unequal allelic expression.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by
      inactivation of neurofibromin, a protein capable of modulating signal
      transduction by activating Ras-GTPase activity. We have used cDNA cloning and
      Northern blot analysis to confirm the NF1 gene produces alternatively
      polyadenylated mRNAs with 3' untranslated regions (3' UTR) that show striking
      evolutionary conservation. Scanning of the 3'UTRs for genetic variation revealed
      three common sequence polymorphisms (> 30% heterozygosity), one less informative
      polymorphism (approximately 5% heterozygosity) and one rare variant (1/144
      chromosomes). These differences were used to examine relative levels of
      expression of normal and mutant NF1 alleles in lymphoblast cell lines and in one
      case, autopsy tissue, from patients with NF1. Unequal allelic expression (up to 4
      fold) was observed in a subset of both sporadic and familial NF1 cases. Where
      linkage phase could be determined, the allele segregating with the disorder
      displayed a relative reduction in expression. However, the magnitude of this
      effect was variable suggesting the operation of additional, non-genetic factors
      in determining the degree of relative expression of the mutant allele.

PMID- 9919312
TI  - A matrix associated region localizes the human SOCS-1 gene to chromosome
      16p13.13.
AB  - The MarFinder algorithm was applied to a newly sequenced segment of 16p13.13
      abutting the 3' end of the human PRM1-->PRM2-->TNP2 locus. A candidate region of
      matrix attached was identified. Subsequent biophysical analysis showed that this
      region was attached to the somatic nuclear matrix. Nucleotide sequence analysis
      also revealed the presence of a CpG island. Data base queries showed that this
      region contained the SOCS-1 gene. Thus, the SOCS-1 gene is bounded by a somatic
      MAR and is just 3' of the spermatid-expressed PRM1-->PRM2-->TNP2 domain at
      position 16p13.13.

PMID- 9919311
TI  - Molecular cloning of a zinc finger gene eZNF from a human inner ear cDNA library,
      and in situ expression pattern of its mouse homologue in mouse inner ear.
AB  - We have isolated and characterized the cDNA for eZNF, a zinc finger gene
      expressed in human inner ear, from a kinetically enriched human inner ear cDNA
      library. The sequence of full length cDNA was determined and its expression
      pattern characterized. A high degree of homology is shared between eZNF and rat
      transcription factor Kid-1. It belongs to the C2H2 class of zinc finger genes,
      contains a Kruppel-associated box (KRAB) domain near the N-terminus, and has
      consensus sites for phosphorylation. The gene is expressed in kidney and inner
      ear structures of mouse and human as determined by Northern blot analysis. In
      situ hybridization was used to demonstrate specific expression of the mouse eZNF
      homologue in epithelial layers of the saccule, semicircular canals, and the
      cochlea of newborn mice. The genomic clone corresponding to the cDNA was isolated
      and used for fluorescence in situ hybridization to localize it to human
      chromosome 5qter. The identification of genes expressed in human inner ear by
      representational difference analysis, their chromosomal location, and expression
      pattern of their homologues in developing mouse inner ear comprise a strategy
      that can potentially identify genes important in hearing and deafness.

PMID- 9919313
TI  - Toward expression mapping of albinism-deafness syndrome (ADFN) locus on
      chromosome Xq26.
AB  - We have employed a direct cDNA selection methodology to isolate transcribed
      sequences encoded in the human chromosomal interval Xq26 that contains the gene
      for X-chromosome linked albinism deafness syndrome (ADFN). ADFN had been
      previously mapped to an 8 centi Morgan region on chromosome Xq26. We have
      constructed six cDNA libraries specific to six YACs mapping to a 1.5 mb span at
      the distal boundary of the ADFN locus. The YAC specific libraries were
      characterized for the presence of unique cDNAs. We have identified 15 transcribed
      sequences from the selected cDNA libraries. These cDNAs matched to three well
      characterized sequences corresponding to steroid 5-alpha reductase, ribosomal
      protein L28, and a short transcript that has been shown to be expressed in human
      brain cortex. Seven of the cDNAs matched to expressed sequence tags or other
      sequences of unknown function, and five cDNAs shared no homology with sequences
      in the public data bases. Each one of these sequences was represented as 3-10
      clones in the set that was subjected to sequencing. Further characterization of
      these transcribed sequences may indicate potential candidates responsible for
      ADFN. We have discussed the utility of cDNA selection methodology in assembling
      transcript maps and identifying potential candidates for genetic deafness.

PMID- 9919314
TI  - Human potential phases in the second half of life.

PMID- 9919315
TI  - The association between depression and disability.

PMID- 9919316
TI  - The impact of OBRA '87 on psychiatric services in nursing homes. Joint testimony
      of the American Psychiatric Association and the American Association for
      Geriatric Psychiatry.
AB  - The Institute of Medicine has formed a Committee on Improving Quality in Long
      Term Care, which is examining the legislative and quality-of-care impact that the
      Omnibus Budget Reconciliation Act of 1987 (OBRA '87) had on long-term care. The
      American Psychiatric Association and the American Association for Geriatric
      Psychiatry were asked to provide written and oral testimony before the Committee
      in March 1998. The two organizations summarized the key outcomes of OBRA '87 on
      the psychiatric needs of individuals who receive services in long-term care
      settings. The written testimony also encouraged the Committee to insist that the
      long-term care industry develop, test, and refine psychiatric and mental health
      quality outcome measures for nursing facilities and other long-term care
      settings.

PMID- 9919317
TI  - Testosterone and depression in aging men.
AB  - In men, testosterone secretion affects neurobehavioral functions such as sexual
      arousal, aggression, emotional tone, and cognition. Beginning at approximately
      age 50, men secrete progressively lower amounts of testosterone; about 20% of men
      over age 60 have lower-than-normal levels. The psychiatric sequelae are poorly
      understood, yet there is evidence of an association with depressive symptoms. The
      authors reviewed 1) the physiology of the hypothalamic-pituitary-gonadal axis and
      its changes with age in men; and 2) the evidence linking testosterone level and
      major depression in men. Data on this relationship are derived from two types of
      studies: observational studies comparing testosterone levels and secretory
      patterns in depressed and non-depressed men, and treatment studies using
      exogenous androgens for male depression. The data suggest that some depressed
      older men may have state-dependent low testosterone levels and that some
      depressed men may improve with androgen treatment.

PMID- 9919318
TI  - Disability in geriatric depression.
AB  - The authors examined impairment in self-maintenance skills and in instrumental
      activities of daily living (IADL) among 211 older patients with unipolar major
      depression. In regression models, self-maintenance impairment was associated with
      older age, less reported depressed mood, psychomotor retardation, and severe
      chronic medical illness. IADL deficit was associated with older age, greater
      severity of depression, less guilt, more apathy, weight loss, greater cognitive
      impairment, more severe chronic medical illness, less social interaction, lower
      subjective social support, and greater instrumental support. The authors conclude
      that efforts to remediate basic skills deficits in depressed older adults should
      focus on treating comorbid medical conditions; impaired IADL skills in geriatric
      depressed patients should improve with treatment of depression and medical
      illness. Clinicians should be aware that substantial IADL impairment may
      accompany mild cognitive impairment associated with depression in older patients.

PMID- 9919319
TI  - EEG sleep measures in later-life bereavement depression. A randomized, double
      blind, placebo-controlled evaluation of nortriptyline.
AB  - The authors examined 1) effects of nortriptyline (NT) on electroencephalographic
      (EEG) sleep measures in elderly patients with bereavement-related depression in
      remission under randomized, double-blind, placebo-controlled conditions, and 2)
      the effects of clinical remission on sleep after discontinuation of medication.
      Subjects were classified as responders to placebo (n = 9) or NT (n = 18) and had
      EEG sleep studies at three time-points: before treatment (T1), remitted on
      medication or placebo (T2), and remitted off medication or placebo (T3). As
      compared with placebo, NT was differentially associated with decreases in REM
      sleep time and percent and increases in REM sleep density (T2). No changes in EEG
      sleep measures occurred in placebo responders. REM sleep measures in NT
      responders reverted to T1 levels after T3, with persistence of robust clinical
      remission and normal subjective sleep quality. These data suggest that NT alters
      REM sleep, but that EEG sleep characteristics in bereavement-related depression
      persist into remission.

PMID- 9919320
TI  - Use of health services by medically ill depressed elderly patients after hospital
      discharge.
AB  - The authors evaluated a consecutive sample of 542 elderly hospital patients for
      depression; of these, 160 depressed and 171 nondepressed patients were followed
      up for a median of 47 weeks after discharge. A subset of 113 depressed patients
      had significant physical disability. Depressed patients saw physicians more
      frequently, particularly during the 9- to 12-month period after hospital
      discharge. Depressed patients also had higher rates of rehospitalization and
      spent more days in the nursing home. These findings persisted after physical
      health status was controlled. Patients who remained both depressed and physically
      disabled during the follow-up period used the most general-medical services
      during the year after hospital discharge, but did not see mental health
      specialists any more frequently than those whose depression and physical
      disability improved. These results underscore the importance of diagnosing and
      treating depression during and after hospital discharge to increase quality of
      life and possibly reduce health service use.

PMID- 9919321
TI  - Racial differences in neuropsychiatric symptoms among dementia outpatients.
AB  - This study, based on evaluations of 240 outpatients with Alzheimer's disease or
      multi-infarct dementia, examines whether race has any independent effects on the
      prevalence and levels of related neuropsychiatric symptoms. After the authors
      controlled for 14 potentially confounding variables, race had a significant
      independent effect on the levels of psychotic and depressive symptoms, the former
      being greater among blacks and the latter among whites. There were no differences
      in symptoms between U.S.-born African Americans and African Caribbeans. Although
      it is likely that racial differences reflect variations in symptoms brought in
      for evaluation, the absence of intraracial differences suggests the possibility
      of an underlying biological process.

PMID- 9919322
TI  - Treatment of 70(+)-year-olds with recurrent major depression. Excellent short
      term but brittle long-term response.
AB  - The authors compared response rates, by age (60-69 vs. 70+), to acute,
      continuation, and 1-year maintenance depression treatment. Patients (N = 180)
      received open combined treatment with nortriptyline (NT)/placebo and
      interpersonal psychotherapy (IPT). Patients who recovered then entered
      randomized, double-blind maintenance treatment with NT or placebo or received
      maintenance monthly IPT (combined with NT or placebo). Comparison of time-to
      remission and recovery and absolute rates of remission, relapse, recovery, and
      recurrence yielded similar times to/rates of remission and recovery; however,
      older patients had far more recurrence during the first year of maintenance
      therapy. Although responses to acute and continuation treatment with combined NT
      and psychotherapy were similar, the older group had more recurrence in the first
      year of maintenance. Continuation of combined medication and psychotherapy may
      represent the best long-term treatment.

PMID- 9919324
TI  - Age at onset in geriatric bipolar disorder. Effects on clinical presentation and
      treatment outcomes in an inpatient sample.
AB  - The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for
      bipolar disorder, divided into early- and late-onset groups by their median age
      at lifetime onset, 49 years, in order to examine differences in demographic and
      clinical characteristics, treatment parameters, and outcome in the two groups
      during a short-term hospitalization. The late-onset group was more likely to have
      psychotic features and to demonstrate cerebrovascular risk/burden. However, both
      groups had similar and highly significant improvements in the Brief Psychiatric
      Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87%
      were able to be discharged to settings no more restrictive than those at
      admission.

PMID- 9919325
TI  - Gynaecologic oncology--the next lap.

PMID- 9919323
TI  - Conventional vs. newer antipsychotics in elderly patients.
AB  - Elderly patients with schizophrenia and dementia patients with agitation are
      frequently candidates for antipsychotic treatment. Conventional neuroleptics have
      relatively little effect on negative symptoms and may cause considerable side
      effects, especially in elderly patients. The authors have found a 29% cumulative
      annual incidence of tardive dyskinesia (TD) in middle-aged and elderly
      outpatients treated with relatively low doses of conventional neuroleptics Newer
      antipsychotics are less likely to cause extrapyramidal symptoms and may be
      associated with a lower risk of TD. They are generally effective for both
      positive and negative symptoms and may also improve some aspects of cognition,
      but these drugs have their own side effects. Dosing requirements for elderly
      patients tend to be much lower than those for younger adults.

PMID- 9919326
TI  - Outcome of early cervical carcinoma treated by Wertheim hysterectomy with
      selective postoperative radiotherapy.
AB  - Seventy-five consecutive patients with histologically confirmed FIGO stage IB-IIA
      cervical carcinoma who underwent Wertheim hysterectomy were studied
      retrospectively. Poor prognostic factors were found in 42 (56%) patients in whom
      postoperative adjuvant pelvic irradiation was given. The overall disease-free
      survival rate was 78% at 5 years and 75% at 9 years. The tumour recurrence rate
      was 12.1% in the low-risk patients and 35.7% in the high-risk patients. Tumour
      recurrences occurred significantly more frequently in patients with tumours with
      high grade squamous cell carcinomas and adenosquamous carcinoma. No recurrences
      occurred in patients with adenocarcinomas. After adjuvant radiotherapy, there was
      no statistically significant difference in the recurrence rates between lymph
      node positive and negative patients (26.7% and 19.6% respectively), however
      extrapelvic recurrences were more common in those with diseased lymph nodes. The
      recurrence rate was 40% in patients with involved resection margins compared to
      16.7% of patients with clear margins. The recurrence rates were similar for
      patients with and without tumour embolisation of vascular/lymphatic channels.
      Wertheim hysterectomy with postoperative pelvic irradiation for selected high
      risk patients was an effective treatment for FIGO stage IB-IIA cervical
      carcinoma. Despite radiotherapy, the high-risk patients still experienced a high
      tumour recurrence rate.

PMID- 9919327
TI  - A review of patients with high-risk carcinoma of the cervix treated with combined
      surgery and postoperative radiotherapy.
AB  - From May 1992 to October 1995, 57 patients with early stage cervical carcinoma
      were treated with hysterectomy and postoperative pelvic radiotherapy because of
      the presence of adverse histopathologic features. On prospective follow-up and
      analysis, the clinical outcome for 50 of these patients showed a pelvic disease
      control rate of 90.9%, a disease-free survival of 80.6% and an overall survival
      of 86.3%. Of the 8 relapses, half occurred in the pelvis i.e., 2 in the vaginal
      vault and 2 in the pelvic side walls. No severe complications were observed, but
      there was a 20% long-term Radiation Therapy and Oncology Group (RTOG) grade 1 to
      2 urinary bladder dysfunctional problem and 28% incidence of suprapubic and/or
      leg oedema.

PMID- 9919328
TI  - Adjuvant chemotherapy in "high risk" patients after Wertheim hysterectomy--10
      year survivals.
AB  - Although the primary operative mortality following radical hysterectomy for stage
      IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in
      those patients with histological evidence of "risk" features--lymph node
      metastases, lymphatic vascular tumour permeation and clinically undetected
      parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with
      stage IB and early IIA disease had radical hysterectomy and pelvic
      lymphadenectomy. One hundred and eight patients (45.2%) had various poor
      prognostic histological features and received adjuvant chemotherapy--70 had
      cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others
      received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk
      factors present in each group were identical. These patients have now been
      followed up for periods ranging from 8 to 14 years. All recurrences, except one,
      occurred within 23 months of surgery; in the remaining this occurred 8 years
      later. This suggests that very close long-term follow-up is needed. Recurrences
      were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The
      10-year survival in patients without risk factors was 97.2%. In those patients
      with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant
      chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year
      survivals in patients with positive nodes were similar--66.7% in the MMC group
      and 71.4% in the PVB group. The 10-year survival in patients with squamous cell
      carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU)
      group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in
      patients with adenocarcinoma and adenosquamous carcinoma was significantly better
      (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%)
      (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for
      patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those
      with adenocarcinoma, the PVB regime.

PMID- 9919330
TI  - Outcome of obstructive uropathy after pelvic irradiation in patients with
      carcinoma of the uterine cervix.
AB  - The natural history and outcome of intervention for obstructive uropathy were
      studied retrospectively in 20 patients managed at the Department of Urology,
      Singapore General Hospital between 1991 and 1997. The diagnoses of these
      strictures were made between 10 months and 21 years after the initial treatment.
      There were 9 (45%) malignant and 11 (55%) benign strictures. The site of ureteric
      obstruction was in the lower ureter in 15 patients, in the middle ureter in 3
      patients and in the upper ureter in 2 patients. Comparisons between malignant and
      benign strictures showed that patients with higher original stage of tumour were
      more likely to have malignant strictures. Besides latency period between primary
      treatment of the tumour and diagnosis of uropathy, bilaterality and site of
      strictures showed no discernible difference between benign and malignant
      strictures. Ureteric stenting provided good outcome in 5 patients with benign
      strictures and in 3 patients with malignant strictures. Open surgical
      reconstruction was performed on 2 patients with benign strictures and 2 patients
      with malignant strictures. All these four patients showed good outcome. Ureteric
      stenting is an acceptable treatment of benign ureteric stricture and for selected
      patients with malignant strictures. Open surgery is recommended in patients with
      benign strictures who could not be treated successfully on stenting.

PMID- 9919329
TI  - The surgical management of colorectal complications from irradiation for
      carcinoma of the cervix.
AB  - Bowel injury from radiation given for carcinoma of the cervix is a complex
      management problem. Prospectively collected computerized data from April 1989 to
      June 1997 (8 years) were analysed. There were 84 women with a mean age of 60.6
      (standard error 1.2) years. Bleeding from radiation proctitis presented much
      earlier [mean 19.9 (1.9) months after radiotherapy] than either strictures [mean
      81.9 (18.4) months, P = 0.008] or rectovaginal fistula [mean 95.5 (39.0) months].
      Topical formalin application successfully controlled bleeding in 49 of 55
      patients (89.1%) with radiation proctocolitis. The remaining 6 patients, as well
      as all 14 patients with symptomatic strictures and all 14 patients with
      rectovaginal fistula underwent surgery. Rectal strictures were successfully
      dilated in 2. Bowel resection with reanastomosis (with stoma defunction) was
      performed in 12 and stoma was created in the remaining 20 because of poor general
      medical condition or advanced recurrent malignancy. The postoperative mortality
      was 3% (1 bronchopneumonia) and morbidity was 9% (1 anastomotic leak, 1 urinary
      infection and 1 wound infection). At a mean follow up of 35 (2.4) months, 7
      (21.2%) other postoperative patients have since died (all of these from recurrent
      cancer). We conclude that topical formalin is effective for controlling bleeding
      radiation proctitis. When not successful or where other radiation complications
      occur, judicious surgery dependent upon the patient's general condition can be
      safely and effectively performed. The longer term results are worthwhile,
      especially where there is no recurrent cancer.

PMID- 9919331
TI  - Radiotherapy as local adjuvant treatment for endometrial carcinoma--a review of
      45 patients.
AB  - Forty-five patients with endometrial carcinoma were treated with local
      postoperative adjuvant radiotherapy during the period 1992 to 1995. Radiotherapy
      technique comprised both external beam irradiation as well as high-dose-rate
      vaginal vault brachytherapy. The 5-year overall survival and relapse-free
      survival rates were 74% and 73%, respectively and poorly differentiated histology
      grade was associated with poorer prognosis. Only 1 patient developed an isolated
      vaginal vault recurrence and another 9 patients relapsed mainly at the distal
      anatomical sites. The main radiotherapy-related complications were vaginal
      adhesion and stenosis. Radiotherapy is therefore effective as local adjuvant
      treatment in reducing risk of local-regional relapse in endometrial carcinoma.

PMID- 9919332
TI  - Uterine papillary serous carcinoma--the KK Hospital experience.
AB  - A review of 355 cases of endometrial cancer treated at the KK Gynaecological
      Cancer Centre from June 1987 to June 1997 revealed 19 cases (5.3%) of uterine
      papillary serous carcinoma (UPSC), a clinically aggressive and pathologically
      distinct variant of adenocarcinoma which closely resembles ovarian papillary
      serous carcinoma. The majority of UPSC presented as late stage disease with 79%
      showing extrauterine disease. Twelve of 15 patients also had lymphovascular space
      invasion. Of the 19 cases, 15 had total hysterectomy and bilateral salpingo
      oophorectomy with or without omentectomy and lymphadenectomy. Two had omental
      biopsy only and another 2 had dilatation and curettage only. The overall median
      survival in the series was 15 months. Twelve patients had died of disease (67%).
      Early stage disease seemed to confer a better prognosis. The poor prognosis is
      frequently ascribed to its tendency to present at a late stage.

PMID- 9919333
TI  - Single agent paclitaxel in resistant and relapsed epithelial ovarian cancer after
      first-line platinum-based chemotherapy--experience in an Asian population.
AB  - The efficacy and toxicity profile of paclitaxel (Taxol) was studied in 33
      Singaporean women with epithelial ovarian carcinoma who had either failed to
      respond or relapsed after an initial response to first-line chemotherapy with
      combined platinum and cyclophosphamide. Paclitaxel was given intravenously as a
      single agent at a dose of 200 mg/m2 over 3 hours, with standard pre-medication,
      at 4 weekly intervals. A total of 102 cycles were administered. The median number
      of cycles was 3 (range 1 to 8) per patient. Twenty-six patients were eligible for
      response evaluation. Six (23.2%) patients showed a complete response and 4
      (15.4%) showed a partial response. Two (7.7%) patients had stable disease and 14
      (53.8%) patients had progressive disease. The response rate was 22.2% (2 of 9
      patients) for patients with progressive disease while on the first-line platinum
      based chemotherapy, 37.5% (3 of 8 patients) for patients with response-relapse
      interval of less than 6 months, 40.0% (2 of 5 patients) for patients with
      response-relapse interval of 6 to 12 months, and 75% (3 of 4 patients) for
      patients with response-relapse interval of more than 12 months. The median
      duration of survival was 10 months for the entire cohort of patients, but all
      complete responders and 75% of partial responders survived the duration of the
      study period of 24 months, compared to 50% of patients with stable disease and 7%
      of patients with progressive disease. Toxicity of paclitaxel treatment was
      evaluated in 102 cycles. Grade 3 or 4 alopecia, grade 1 or 2 sensory peripheral
      neuropathy and mild facial flush occurred in all patients. Haematological
      toxicity was mild, with 9.8% of the cycles complicated by grade 3 or 4
      neutropenia. Bone marrow suppression was of short duration. No treatment delay or
      dose modification was needed. It is concluded that the effectiveness of
      paclitaxel for salvage treatment of patients with resistant or relapsed
      epithelial ovarian carcinoma after first-line platinum-based chemotherapy among
      Asian patients is comparable to that reported in Western populations. The
      treatment was well tolerated by our patients. It should be considered the
      chemotherapy of choice for patients with relapsed ovarian cancer after prior
      platinum-based chemotherapy.

PMID- 9919334
TI  - A phase II study of combined CPT-11 and mitomycin-C in platinum refractory clear
      cell and mucinous ovarian carcinoma.
AB  - This article reviews the preliminary but encouraging clinical data obtained from
      patients with platinum-refractory clear cell or mucinous carcinoma of the ovary
      who were treated with a chemotherapy regimen including irinotecan hydrochloride
      (CPT-11). Twenty-five patients with platinum-refractory macroscopic disease of
      which histologic type was either clear cell or mucinous carcinoma were treated.
      CPT-11 was administered at a dose of 120 mg/m2 intravenously (i.v.) over 4 hours
      on days 1 and 15, and mitomycin-C (MMC) was given IV as a bolus at a dose of 7
      mg/m2 on days 1 and 15. At least 2 cycles of this regimen, 4 weeks apart, were
      given to the 25 patients. After a median of 4 cycles (range 2 to 8), we observed
      objective responses in 13 patients (52%), with 5 complete responses (CRs; 20%)
      and 8 (32%) partial responses (PRs) (95% confidence interval, 32.4% to 71.6%,
      4.3% to 35.7%, 13.7% to 50.3%, respectively). The median overall survival time
      for all 25 patients was 15.3 months (range 3.5 to 38.0). Median overall survival
      time of the responders was 33.7 months versus 6.1 months of the non-responders
      (Log-rank, P = 0.0003). The median progression-free survival times for patients
      obtaining CR, PR, and CR+PR were 31.8 months (range 12.9 to 34.4), 10.5 months
      (range 5.6 to 18.2), and 12.9 months (range 5.6 to 34.4), respectively. Toxic
      effects were acceptable and included manageable haematologic reactions,
      diarrhoea, nausea/vomiting, and alopecia.

PMID- 9919335
TI  - Malignant ovarian germ cell tumours: experience in the National University
      Hospital of Singapore.
AB  - Management of thirteen cases of malignant ovarian germ cell tumours was reported.
      Of these, 5 (38%) were immature teratoma, 3 (23%) were endodermal sinus tumour, 1
      (8%) was dysgerminoma and 4 (31%) were mixed germ cell tumour. Eight (61%) had
      stage I, 1 (8%) had stage II and 4 (31%) had stage III diseases. Six had
      unilateral salpingo-oophorectomy, 6 had total abdominal hysterectomy and
      bilateral salpingo-oophorectomy and 1 had bilateral oophorectomy. Ten (77%) had
      adjuvant chemotherapy predominantly with bleomycin/etoposide/cisplatin
      combination. All patients with stage I and stage II tumours were alive with no
      evidence of disease at 1/2 year to 5 years followup. Of the 4 patients with stage
      IIIC diseases, 2 with optimal debulking surgery were alive and disease free at 4
      and 7 years after surgery. The other 2 patients with stage IIIC tumours had
      multiple bulky residual tumours. One of them with a combination of endodermal
      sinus tumour and embryonal carcinoma died of progressive disease despite
      chemotherapy 6 months after surgery and the other with mixed endodermal sinus
      tumour and dysgerminoma was alive with disease at 6 months. Alpha-fetoprotein
      levels were raised in all 6 patients with endodermal sinus tumour, either pure or
      combined with other tumours. Regression of alpha-fetoprotein levels was of
      important prognostic significance in endodermal sinus tumour.

PMID- 9919336
TI  - Adenocarcinoma of the cervix.
AB  - With the impact of screening programmes in reducing the incidence of squamous
      carcinoma of the cervix it is timely that attention is concentrated on glandular
      lesions. There is convincing evidence that adenocarcinoma of the cervix is
      increasing in incidence, and this may be related to either oral contraceptive
      use, human papillovirus infections, or both. Compared to its squamous cancer
      counterpart the response to therapy, particularly irradiation, is less than
      optimal, and it is clear that multicentre randomised trials are urgently required
      to delineate the optimal management of women with this disease.

PMID- 9919337
TI  - The management dilemma of the mildly abnormal smear: fact or fiction?
AB  - For at least 10 years, there has been much controversy regarding the management
      of women presenting with a first mildly dyskaryotic cervical smear. Argument has
      centred on many key issues, including the risk of progression to more serious
      disease, the anxiety caused to the patient, the risk of overtreating patients
      with minor disease and, more recently, the financial implications of prompt
      intervention and treatment. Essentially, it has been established for many years
      that only two main management options are appropriate. The first is a policy of
      referring all patients with mild dyskaryosis for prompt colposcopy and
      intervention. The second option is to keep such patients under cytological
      surveillance, with recourse to colposcopy only if the lesion persists or
      progresses on subsequent cytological screening. This review article aims at
      appraising the evidence that is currently available in an attempt to try and
      resolve the management dilemma posed by a mildly abnormal smear.

PMID- 9919338
TI  - Biomarkers in carcinoma of the cervix: emphasis on tissue-related factors and
      their potential prognostic factors.
AB  - Despite the introduction of the PAP smear screening technique, cervical carcinoma
      continues to be a significant disease worldwide in terms of prevalence, morbidity
      and mortality. This paper reviews the prognostic value of biomarkers from some
      oncogenes, including c-myc, ras and c-erb B-2, the cellular proliferation markers
      PCNA and Ki-67, and other more recently described biomarkers such as nm23-H1, MN
      protein and metalloproteinase. Emphasis is given at a practical level to markers
      which can preferentially be applied to tissue sections rather than involving
      other modalities of investigation which may require specialised equipment and
      technology. No single marker of those previously listed was found to have
      outstanding prognostic significance. Although some have shown promise in initial
      studies subsequent investigations have not provided corroborating evidence, or,
      in some situations, have also led to conflicting results. Difficulties inherent
      in establishing the prognostic value of individual markers also include the
      multifactorial complexity of cervical carcinogenesis itself. The future awaits a
      greater amount of data to be accrued across all stages of disease, with improved
      standisation of results.

PMID- 9919339
TI  - Screening for ovarian cancer.
AB  - Ovarian cancer is predominantly a disease of postmenopausal women which presents
      at a late stage and has an overall 5-year survival of less than 30%. If detected
      at stage I, survival is dramatically increased and this would suggest that
      screening for ovarian cancer may reduce mortality. However, the inaccessibility
      of the ovaries and the absence of a confirmed premalignant condition make
      screening for preclinical disease difficult. Recent advances in tumour marker
      interpretation and ultrasound technology have now allowed screening for ovarian
      cancer to become a real possibility. CA 125 is the most widely used tumour marker
      for ovarian cancer and it has been shown to be elevated several years before
      clinical presentation. A new approach to the interpretation of sequential CA 125
      results, which uses a mathematical algorithm to determine an individual's risk of
      cancer, has improved the sensitivity of CA 125 in screening asymptomatic
      postmenopausal women. Screening using transvaginal ultrasound, Doppler and
      morphological indices gives encouraging results but, used alone, it currently
      lacks the specificity required of a screening test for the general population.
      Multimodal screening using tumour markers and ultrasound in combination gives
      high sensitivity and specificity and is also the most cost-effective potential
      screening strategy. The sensitivity and specificity of these techniques are
      sufficient to warrant large-scale clinical trials of ovarian cancer screening.
      Three such trials are currently underway and, in due course, will establish
      whether any screening strategy will ultimately reduce mortality from ovarian
      cancer.

PMID- 9919340
TI  - Topoisomerase-I inhibitors in gynaecologic tumours.
AB  - Topoisomerase inhibitors have been studied using various dose schedules in the
      treatment of refractory or recurrent gynaecologic cancers. Response rates are
      between 13% and 20%. Main toxic effects are haematologic and gastrointestinal.
      The latter remains problematic. Radiotherapy, alkylate, platinum analogs and
      topoisomerase II inhibitors are currently being studied in combination with
      camptothecins.

PMID- 9919341
TI  - Current management of early vulvar cancer.
AB  - In recent years, vulvar cancer management has been revolutionised with a more
      conservative approach being recommended for the primary lesion, and a more
      rational approach to the management of the lymph nodes. Treatment has become
      individualised with consideration being given independently to the optimal
      approach for the primary lesion and regional lymph nodes. The primary vulvar
      lesion can be effectively treated by radical local excision, thereby sparing the
      psychosexual consequences of radical vulvectomy in most patients. Local
      recurrence occurs in up to 10% cases whether or not radical vulvectomy has been
      performed, and can usually be effectively treated by further surgery and/or
      radiation. By contrast, recurrence in the groin is usually fatal, so any patient
      with a T1 lesion and more than 1 mm stromal invasion should have at least an
      ipsilateral inguinal-femoral lymphadenectomy performed. Postoperative groin and
      pelvic radiation should be given for patients with 3 or more micrometastases in
      lymph nodes, one macrometastasis (> or = 10 mm diameter), or any evidence of
      extracapsular nodal spread. The future role of lymphatic mapping to decrease the
      morbidity associated with complete inguinal-femoral lymphadenectomy awaits
      further investigation.

PMID- 9919342
TI  - Fallopian tube carcinoma--a review.
AB  - Although a common site of metastases, primary fallopian tube carcinoma comprises
      only 0.3% of all gynaecological malignancies. Presenting symptoms are variable
      and non-specific, with preoperative diagnosis rarely entertained. The FIGO system
      assigns nearly two-thirds of patients to stage I or II and is based on surgical
      staging criteria similar to those for ovarian cancer. Likewise, management is
      based on that for ovarian cancer-radical debulking followed by platinum-based
      combination chemotherapy. Five-year survival for patients with disease confined
      to the tube at diagnosis (stage I) is only about 60% and only 10% of patients
      with advanced disease will be cured.

PMID- 9919343
TI  - Optimal treatment in gestational trophoblastic disease.
AB  - Gestational trophoblastic diseases are a heterogenous group of conditions ranging
      from the benign hydatidiform mole to the malignant choriocarcinoma. Optimal
      therapy in this group of diseases rest in the correct diagnosis, assessing their
      risk for malignant behavior using prognostic scoring systems and administering
      appropriate treatment. Their rarity makes it imperative that these patients are
      treated in special centres by experts. Benign moles are treated surgically with
      evacuation of the uterus or hysterectomy. In malignant gestational trophoblastic
      disease, chemotherapy is the treatment of choice; single agent for non-metastatic
      and low-risk metastatic disease and combination chemotherapy for high-risk
      metastatic disease. Judicious use of surgery and radiotherapy in these cases will
      improve the survival rate. With appropriate treatment, the cure rates approach
      100% in the low-risk group and 80% to 85% in the high risk group.

PMID- 9919344
TI  - A case report--delayed vesicocutaneous fistula after radiation therapy for
      advanced vulvar cancer.
AB  - This is the first case report of a vesicocutaneous fistula related to prior
      radiation therapy for recurrent vulvar cancer. Urinary tract complications happen
      not infrequently after radiation therapy for various pelvic malignancy. It can
      occur as long as 30 years after cessation of such therapy. Urinary incontinence
      or obstructive uropathy is, by far, the most common complication. The authors
      report an unusual complication secondary to radiation therapy. The aetiology,
      presentation and management of this patient were discussed.

PMID- 9919345
TI  - Repair of complex ureterovaginal and vesicovaginal fistulas with ileal
      cystoplasty and ureteric reimplantation into an antireflux ileal nipple valve--a
      case report.
AB  - We report a case of a 59-year-old woman with bilateral ureterovaginal and
      vesicovaginal fistulas after radical total hysterectomy and bilateral salphingo
      oophorectomy who failed transvesical repair of the vesicovaginal fistula. The
      bladder was extensively scarred, half of which had to be excised. This was
      replaced with an ileal cystoplasty with an antireflux ileal nipple valve into
      which the ureters were reimplanted. Continuity of the urinary tract was re
      established without a urinary diversion or stoma.

PMID- 9919346
TI  - Pelvic spleen masquerading as an ovarian neoplasm.
AB  - A case of a 53-year-old perimenopausal woman who presented with an 18-month
      history of irregular vaginal bleeding is reported. Vaginal ultrasonography
      revealed a 10 x 7 cm pelvic mass with an increased blood flow. Her serum CA125
      was within the normal range. At laparotomy a normal spleen was found within the
      pelvic cavity.

PMID- 9919347
TI  - Occult virilizing ovarian tumours in postmenopausal women: problems in evaluation
      with reference to a case.
AB  - A 53-year-old postmenopausal presented with hirsutism, acne, receding hairline,
      male-pattern baldness, and deepening of voice developing over the last five
      years. Her left ovary had been removed at the age of 38 years old for a benign
      cyst and vaginal hysterectomy was performed one year later for cervical
      carcinoma. She had taken premarin 0.625 mg daily since her surgeries. Initial
      hormonal studies revealed elevated serum concentrations of total testosterone 524
      ng/dL (N: 6-86 ng/dL), free testosterone 20.9 pg/mL (N: 0.3-2.7 pg/mL), and 17
      hydroxyprogesterone 270 ng/dL (N: < 70 ng/dL); but normal baseline concentrations
      of dehydroepiandrosterone-sulfate, androstenedione, and cortisol. Computed
      tomographic (CT) scans of the adrenals and ultrasonography of the pelvis were
      negative. Magnetic resonance imaging (MRI) of the abdomen and pelvis similarly
      were non-revealing. She was given glucocorticoids without effect. Subsequently,
      retrograde selective venous sampling showed a marked testosterone gradient in the
      right ovarian vein. A laparoscopic right oophorectomy was performed and a 11 mm
      Leydig cell tumour of hilus cell type was detected on histologic examination.
      Postoperative testosterone levels returned to normal and she had slow regression
      of hirsutism. Our case illustrates that a virilizing ovarian neoplasm can be
      small and elude imaging studies. We suggest bilateral oophorectomy for
      postmenopausal women with severe recent-onset virilization and without Cushing's
      syndrome and with normal adrenal imaging. This approach avoids unnecessary
      investigations and delays in definitive management.

PMID- 9919349
TI  - Invasive cancer after treatment of cervical intraepithelial neoplasia.
AB  - This review discusses the risk of invasive cancer following treatment for
      cervical intraepithelial neoplasia (CIN). The emphasis is on methods in current
      use and the risks are calculated with life table methods. Large, long-term follow
      up studies which use life table analysis show clearly that invasive recurrences
      continue to appear at a relatively steady rate for at least 8 years after
      treatment for CIN. The risk remains 4 to 5 times greater than in the background
      population throughout this period. It would seem prudent to continue to offer
      these women increased surveillance with annual smears during this time of
      increased risk. All modern methods of outpatient treatment are highly effective
      in preventing invasive cancer of the cervix if they are used skillfully with an
      understanding of the disease being treated. The thoughtless use of beguilingly
      easy methods will lead only to disaster.

PMID- 9919350
TI  - Experience with a nine-step policy dealing with requests for medically
      inappropriate interventions for cancer.
AB  - The article outlines a nine-step process adopted at The University of Texas MD
      Anderson Cancer Center for handling patient requests for medically inappropriate
      interventions. The main step in the process is review by an Institutional Review
      Committee composed of the physician-in-chief, ethics committee members, and
      medical experts. The decision of the Review Committee is binding. The experience
      with this "futility" policy is discussed including a follow-up pilot project
      conducted by the Department of Gynaecologic Oncology that introduces a
      standardized advance care planning medical record progress note in which patient
      preferences about cardiopulmonary resuscitation, mechanical ventilation, and
      location of death are documented. The note is to be used at the beginning of non
      curative therapy and is intended to help to avoid future requests for futile
      interventions.

PMID- 9919348
TI  - The Polarprobe--emerging technology for cervical cancer screening.
AB  - The Polarprobe is a portable non invasive electronic device designed for the
      detection of cervical precancer and cancer. It measures both electrical and
      optical properties of cervical tissue to allow a real time comparison with a
      databank of previously determined cervical tissue types. The need for additional
      tests to augment or even replace the Papanicolaou smear has partly prompted its
      development. Indeed it has been shown to be associated with less pain and anxiety
      than the smear and has the capability of encouraging women to attend for
      screening. Some of the preliminary clinical trials on the Polarprobe are reported
      as well as the ongoing developments and modifications to the device.

PMID- 9919351
TI  - Postanaesthetic shivering--a comparison of thiopentone and propofol.
AB  - One hundred and sixty patients undergoing minor surgical procedures were randomly
      allocated to receive either thiopentone or propofol for induction of anaesthesia.
      All patients were assessed in the recovery period for the development of
      postanaesthetic shivering. Twenty patients (25%) in the thiopentone group and 8
      patients (10%) in the propofol group developed postanaesthetic shivering (p <
      0.05). There was no statistically significant difference in tympanic temperature
      between shivering and nonshivering patients. Propofol as an induction agent is
      associated with a lower incidence of postanaesthetic shivering as compared to
      thiopentone.

PMID- 9919352
TI  - Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon
      cancer with fluorouracil and levamisole.
AB  - Carcinoma of the large bowel is the second leading cause of cancer mortality in
      Singapore. Although the great majority of patients are discovered at a stage
      where resection with curative intent is possible, almost half of the patients
      afflicted will die of it. The combination of 5-fluorouracil + levamisole used in
      patients with curatively resected high risk Dukes B2 and all Dukes' C colon
      cancers has been shown to reduce cancer recurrence rate and improve overall
      survival. Since 1990 adjuvant chemotherapy has been recommended for this group of
      patients. This report describes patients treated in Singapore, their toxicities
      and their outcome. A total of 341 patients were treated between 1990 and 1996.
      Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2
      nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was
      1 treatment-related death. Median recurrence-free interval was 81 months and
      median survival was not reached at 90 months. This regimen is tolerable. Until
      further randomised reports comparing 5-fluorouracil + levamisole to other
      combinations are available, this combination chemotherapy is recommended to
      patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon
      cancer to reduce cancer recurrence and improve overall survival.

PMID- 9919353
TI  - Emerging therapies for sepsis and septic shock.
AB  - Despite advances in antimicrobial therapy and medical support, septic shock
      remains a leading cause of death. Emerging adjunctive therapy for septic shock
      can be divided into those directed against bacterial components, those directed
      against host-derived inflammatory-mediators and those designed to limit tissue
      damage. All trials of new adjunctive therapies for sepsis and septic shock
      conducted to data have failed to show efficacy. Therapies against endotoxin,
      tumour necrosis factor, interleukin-1 and platelet activating factor did not
      reduce mortality. Future effective therapies will probably use combination of
      agents depending upon the nature of the infection and the type of patient.

PMID- 9919354
TI  - Frontal sinus mucoceles causing proptosis--two case reports.
AB  - Paranasal sinus mucoceles can present with a multitude of different symptoms
      including ophthalmic disturbances. We describe two patients with frontal sinus
      mucoceles presenting with non-axial proptosis, and give details of their
      presentation, investigations and treatment. Possible ocular manifestations of
      mucoceles and the diagnostic imaging techniques used are discussed. The treatment
      of mucoceles is reviewed. It is stressed that a team approach involving the
      ophthalmologist, otolaryngologist and radiologist is essential for accurate
      diagnosis and management.

PMID- 9919355
TI  - Thyroid storm presenting as jaundice and complete heart block.
AB  - Thyroid storm is a difficult diagnosis in "apathetic" variant of hyperthyroidism.
      The clinical features may not be evident. Abnormal atrioventricular (AV)
      conduction, such as complete heart block, in thyrotoxicosis is uncommon. We
      report a case of a 16-year-old girl presenting with fever, jaundice, heart
      failure and complete heart block in whom the diagnosis of thyroid storm was
      initially missed because of the unusual presenting features. Prompt resolution of
      the conduction abnormality occurred when treatment with carbimazole, intravenous
      iodide and dexamethasone was instituted.

PMID- 9919357
TI  - Characterization and expression of the Mx1 gene in wild mouse species.
AB  - The mouse Mx1 gene encodes an interferon (IFN)-inducible nuclear protein and
      confers resistance to influenza virus infection. The standard laboratory mouse
      strains all carry the Mx1- allele and are susceptible to influenza virus. In this
      study, several mouse strains established from wild mice were tested to determine
      their Mx1+ or Mx1- allele status with polymerase chain reaction-restriction
      fragment length variation (PCR-RFLV), sequence analysis, reverse transcription
      (RT)-PCR, and immunofluorescence staining. All of the mouse strains originating
      from wild mice were found uniformly to carry the Mx1+ allele. Therefore, it is
      conceivable that the Mx1+ allele in wild populations serves a function against
      some pathogens related to orthomyxoviruses. The PCR-RFLV and sequence analysis
      allowed us to classify the Mx1+ alleles of the laboratory and wild-origin mouse
      strains into distinct classes. RT-PCR and immunofluorescence staining
      demonstrated that the Mx1 transcripts and proteins were induced by IFN-alpha/beta
      in macrophages from wild mouse species.

PMID- 9919356
TI  - Characterization of lethal Drosophila melanogaster alpha-actinin mutants.
AB  - We have partially characterized four Drosophila melanogaster alpha-actinin gene
      mutants, I(1)2Cb1, I(1)2Cb2, I(1)2Cb4, and I(1)2Cb5. We demonstrate that in each
      case the mutation is caused by a chromosomal rearrangement that precludes normal
      protein synthesis. In the absence of alpha-actinin, flies complete embryogenesis
      and develop into flaccid larvae that die within approximately 24 hr. These larvae
      have noticeable muscle dysfunction at hatching, although they, nevertheless, are
      capable of escaping from the egg membranes and of subsequent crawling movements.
      During larval development muscles degenerate, progressively limiting mobility and
      ultimately causing death. Electron microscopy of mutant muscle fibers reveals
      that myofibrils are grossly disrupted in one day old larvae and that electron
      dense structures reminiscent of those seen in human nemaline myopathies are
      present throughout larval life. Our work rigorously demonstrates that alpha
      actinin deficiencies are the cause of I(1)2Cb muscle defects. We anticipate that
      the alpha-actinin mutants described herein will facilitate in vivo tests of
      spectrin superfamily protein domain functions using a combination of directed
      mutagenesis and germline transformation.

PMID- 9919358
TI  - Expansion of a (GA) dinucleotide at a microsatellite locus associated with
      domestication in rice.
AB  - Microsatellites undergo rapid changes over short evolutionary time periods which
      can be phylogenetically informative in related species. Here we show the repeat
      unit expansion of a (GA)n-type microsatellite in the process of cultivation of
      rice from its wild ancestors. We amplified a microsatellite locus harboring (GA)n
      repeats from several wild and cultivated rices. Sequencing revealed an increase
      in repeat number from 14 in distantly related wild rice species to 24 in the
      widely grown present-day indica rice cultivars.

PMID- 9919359
TI  - Regulation of the expression of the sn-glycerol-3-phosphate dehydrogenase gene in
      Drosophila melanogaster.
AB  - P element-mediated transformation has been used to investigate the regulation of
      expression of the sn-glycerol-3-phosphate dehydrogenase gene of Drosophila
      melanogaster. A 13-kb construct containing the eight exons and associated
      introns, 5 kb of the 5' region, and 3 kb downstream from the structural gene
      produced normal levels of enzyme activity and rescued the poor viability of flies
      lacking the enzyme. All the regulatory elements essential for normal enzyme
      expression were located in a fragment that included the exons and introns and 1
      kb upstream noncoding sequence. Deletions of the 1.6-kb second intron reduced
      activity to 25%. Transformants with fusion constructs between the sn-glycerol-3
      phosphate dehydrogenase gene and the beta-galactosidase gene from E. coli
      revealed three elements that affected expression. A (CT)9 repeat element at the
      5' end of the second intron increased expression in both larvae and adults,
      particularly at emergence. A second regulatory element, which includes a (CT)7
      repeat, was located 5' to the TATA box and had similar effects on the gene's
      expression. A third, undefined, enhancer was located in the second intron,
      between 0.5 and 1.8 kb downstream of the translation initiation codon. This
      element increases enzyme activity to a similar extent in larvae and adults but
      has little effect when the enhancer at the 5' end of the intron is present.

PMID- 9919360
TI  - PCR amplification of a locus with RFLP alleles specific to African honey bees.
AB  - An anonymous honey bee locus, detected previously with a cloned probe, has HhaI
      RFLP alleles specific to African bees or common to both African and European
      bees. To facilitate identification of these alleles, this region, 1231, was made
      analyzable with the PCR. The two halves of the region, excluding the termini,
      were amplified as two overlapping segments. Restriction sites were mapped, and
      the site differences responsible for the allelic RFLP patterns were determined.
      In the first half of the region, two polymorphic HhaI sites are present in the
      common alleles, whereas one, the other, or both of the sites are absent in the
      African alleles. In the second half, a third polymorphic HhaI site is present or
      absent in both common and African alleles. A short part of the second half of the
      region, including more of the terminus, was amplified as a third segment. Within
      this segment, close to this terminus, a fourth polymorphic HhaI site is absent in
      some African alleles.

PMID- 9919361
TI  - Demographic analysis of the veterinary profession in Canada.

PMID- 9919362
TI  - Vaccination protocols for dogs and cats.

PMID- 9919363
TI  - An ethicist's commentary on whether a veterinarian should recommend adding
      antibiotics to feed for growth promotion.

PMID- 9919364
TI  - Effects of intravenously administered glycopyrrolate in anesthetized horses.
AB  - The purpose of this study was to determine the heart rate (HR) and blood pressure
      (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30
      beats/min). The horses were randomly treated with glycopyrrolate (2.5
      micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR
      failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose)
      was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses
      following the initial glycopyrrolate treatment. Overall changes in HR and mean BP
      were not significantly different, while systolic and diastolic BP increased
      significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd
      treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out
      of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart
      rate of > 5 beats/min, which was significant. A significant increase in BP was
      produced following treatment with 2.5 micrograms/kg BW, but not following 5.0
      micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a
      significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an
      increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW,
      i.v., and results in improvement in BP in anesthetized horses.

PMID- 9919365
TI  - Owner response to companion animal death: development of a theory and practical
      implications.
AB  - This study used an inductive research method known as grounded theory to develop
      a theory to describe owner response to the death of a pet. Participants were
      identified from 8 veterinary clinics in Wellington Country, Ontario. Eighty
      percent (8 of 10) of the practices approached agreed to participate and there was
      a 77% (44 of 57) participation rate by clients. Nondirective interviews were
      conducted with participants approximately 10 days following the death of their
      pet, and at 3, 6, and 12 mo thereafter. The theory developed suggests that
      people's reactions are best described as a social and psychological search for
      meaning. Factors that contributed to the search for meaning included societal
      values and norms, the cultural milieu of pet death, and the cultural milieu of
      veterinary medicine. Other factors, such as the participant's personal beliefs,
      life stage, critical life events, and animal attributes, either alleviated or
      aggravated the experience. The outcome for participants grieving the death of a
      pet was a self-governing approach to coping with the death. Practical
      implications and suggestions for veterinarians are presented.

PMID- 9919367
TI  - Paranasal sinus cyst as a cause of stridor in a standardbred colt.
AB  - Sinus cysts are epithelium-lined, fluid-filled cavities that can occur in the
      paranasal sinuses of horses. Extensive damage to the permanent tooth buds was a
      significant feature in this case. The sequellae of these abnormalities, although
      not apparent at the time of presentation, remain an important consideration for
      prognosis.

PMID- 9919366
TI  - Seroepidemiology of undifferentiated fever in feedlot calves in western Canada.
AB  - The relationships between 4 bacterial and 3 viral antibody titers and morbidity
      (undifferentiated fever (UF)) and mortality were investigated in recently weaned
      beef calves. Blood samples from 100 animals that required treatment for UF
      (Cases) and 100 healthy control animals (Controls) were obtained: upon arrival at
      the feedlot (Arrival), at the time of selection as a Case or Control (Selection),
      and at approximately 33 d of the feeding period (Convalescent). Seroconversion to
      Pasteurella haemolytica antileukotoxin was associated with an increased risk of
      UF (OR = 2.83); however, seroconversion to bovine herpesvirus-1 G-IV glycoprotein
      was associated with a decreased risk of UF (OR = 0.43). Higher Arrival bovine
      viral diarrhea virus antibody titer was associated with a decreased risk of UF
      (OR = 0.83). Increases in Mycoplasma alkalescens antibody titer after Arrival
      were associated with an increased risk of UF (OR = 1.10). Higher Arrival
      Haemophilus somnus antibody titer and increases in Haemophilus somnus antibody
      titer after Arrival were both associated with a decreased risk of UF (OR = 0.76
      and OR = 0.78). The odds of overall mortality (OR = 5.09) and hemophilosis
      mortality (OR = 11.31) in Cases were significantly (P < 0.05) higher than in the
      Controls. Higher Arrival bovine herpesvirus-1 antibody titer was associated with
      an increased risk of mortality (OR = 1.30). Protective immunity to Pasteurella
      haemolytica antileukotoxin, Haemophilus somnus, bovine herpesvirus-1 G-IV
      glycoprotein, bovine viral diarrhea virus, and Mycoplasma spp. may be necessary
      to reduce the occurrence of UF. Animals with UF are at an increased risk of
      overall and hemophilosis mortality.

PMID- 9919368
TI  - Isolation of Actinobacillus suis from a cat's lung.
AB  - Actinobacillus suis has been isolated from the lungs of 9-month-old cat. The
      bacterium was characterized biochemically as well as genetically, and its
      sensitivity profile to different antimicrobial agents was established. The role
      of this isolate in the cat's condition is discussed.

PMID- 9919369
TI  - Atypical bacterial gill disease in Atlantic salmon hatcheries in British
      Columbia.

PMID- 9919370
TI  - Onion toxicosis in a herd of beef cows.
AB  - A herd consumed approximately 20 kg onions/cow/day for 6 weeks. Five cows died
      and two aborted. Onion toxicosis results in methemoglobinemia and hemolytic
      anemia. These changes can cause secondary organ damage and death, if enough
      onions are consumed.

PMID- 9919372
TI  - What is your diagnosis and therapeutic plan? Congenital atresia of the left
      nasolacrimal duct.

PMID- 9919373
TI  - Mother-child pass in Austria and primary toxoplasmosis infections in pregnant
      women.
AB  - The mother-child pass (MCP) in Austria, introduced in 1975, has been successful
      till now. The changes and the results of the serological screening for
      toxoplasmosis, included in the MCP over the last 22 years, are demonstrated.

PMID- 9919374
TI  - Active control of congenital toxoplasmosis in the population.
AB  - Repeated serological investigations (CFT, IFT, ELISA) of 50,000 pregnant women
      revealed that 5.1/1000 pregnancies in the Karvina district, Czech Republic are
      threatened by toxoplasmosis. In 2.8/1000 pregnancies the infection was contracted
      shortly before pregnancy, one third of them ended by spontaneous abortion. In
      this group the birth of a congenitally infected infant is rare. Primary
      infections of women who are already pregnant (2.3/1000 of pregnancies) are much
      more serious. This number comprises 1.2/1000 pregnancies with a spontaneous
      abortion and 1.2/1000 pregnancies leading to the delivery of a congenitally
      infected infant. By early detection, i.e. repeated serological examinations in
      all pregnancies, and by treatment of patients with Toxoplasma infections this
      hazard can be reduced substantially, i.e. to one eighth.

PMID- 9919375
TI  - Evaluation of reactogenicity and immunogenicity of two influenza vaccines
      (vaxigrip and fluarix) in the season 1996-1997.
AB  - Influenza is a very serious disease, which causes thousands of deaths all over
      the world every year. As there is so far no sufficiently effective causal therapy
      of influenza the main function of vaccination lies in prevention. Influenza is a
      major problem especially in collective facilities. Therefore, great emphasis is
      laid in the Czech Republic Army on the vaccination of military groups and on the
      evaluation of reactogenicity and immunogenicity of the vaccines used. The
      specific aim of the clinical trial was to evaluate the reactogenicity and
      immunogenicity of two inactivated split influenza vaccines Fluarix and Vaxigrip
      in healthy adult volunteers aged 18-60 years with stress on military groups. The
      study was designed as an open clinical trial with 2 groups each of 100 volunteers
      in one centre. Randomisation was not conducted so that each group received only
      the vaccine specified beforehand. Both the inactivated split vaccines evaluated,
      Vaxigrip and Fluarix are highly immunogenic both against declared and other
      antigenic variants of influenza. The study has demonstrated a favourable trend in
      the preparation of influenza vaccines towards a marked reduction of general
      solicited symptoms as compared with previous years. Despite minute differences in
      immunogenicity and reactogenicity, the vaccines are generally speaking
      comparable, and in healthy individuals aged 18-60 years they induce a sufficient
      protection against the onset and development of influenza. The results of our
      open clinical trial (without randomisation) have again proved that both
      manufacturers produce vaccines of a high European standard.

PMID- 9919376
TI  - Air pollution by particulate matter in the industrialized city of Leoben,
      Austria.
AB  - At seven sites in Leoben, Austria, aerosol particles were sampled in two size
      fractions by a dichotomous sampler using virtual impaction: the fine fraction
      (alveolar aerosol) with an aerodynamic diameter dac < 2.5 microns (PM2.5), and
      the coarse fraction (tracheobronchial aerosol) with an dac between 2.5 and 10
      microns. It is believed that these particles are able to reach the lower regions
      of the human respiratory tract, and thus be responsible for most of the adverse
      health effects associated with suspended particulate pollution. A second sampling
      procedure was made collecting the PM2.5 fraction and after leaching with nitric
      acid, lead, zinc, cadmium, copper, chromium and vanadium were determined with an
      inductively coupled plasma mass spectrometer (ICP-MS). For one sample point a
      third sampling was carried out and both fractions were subsequently leached with
      water and dilute hydrochloric acid. Pb, Zn, Mn, Fe, Cd, Ni, Cu, Rb, Sr, Mo, Cs,
      Ba and Tl were determined by ICP-MS.

PMID- 9919377
TI  - Family and social determinants of school maladjustment in students with emotional
      disturbances and behavioral disorders from recovery schools in Bulgaria.
AB  - This inquiry study is part of a comprehensive investigation on the organization
      and the effect of the education of students with emotional disturbances and
      behavioral disorders in special recovery schools. The aim for conducting the
      inquiry is to reveal the characteristics of the family and social background
      which may affect the school adaptation. The investigated group includes 254
      students--192 with emotional disturbances and behavioral disorders and 62 healthy
      children of the same age from the settlements where the recovery schools are
      based. Two types of questionnaires developed by the team are used for
      investigating the students' family and social status--one designed for the pupils
      and one--for the teachers and supervisors in the schools. The inquiry for the
      students contains 15 questions revealing family and school environment (family
      relations and problems; number of children and sequential number of the problem
      child; parents' education and employment; school training and curriculum; social
      contacts in the school; school results). The inquiry, engaging the class
      teachers, day and night supervisors in recovery schools, contains 19 questions.
      There are additional questions concerning students' specific learning
      difficulties as well. The results made it clear that parents' divorce is the most
      unfavorable family determinant for school maladjustment of students with
      emotional disturbances and behavioral disorders. Many other factors such as the
      poor educational qualification and social-professional status of the parents,
      children number, the sequential number of the problematic child additionally
      impedes the relationship with the parents, thus increasing the risk of school
      failure and the manifestations of school maladjustment. The determined
      peculiarities of the family environment of students with emotional disturbances
      and behavioral disorders suggest targeted psychocorrective work of the school
      psychologist individually with the student as well as with his/her family.

PMID- 9919378
TI  - Mineral concentrations in the blood of male smokers and non-smoking males and
      females measured with fluoro-X-ray analyzer.
AB  - For clarification of the effects of smoking on mineral absorption in red blood
      cells (RBC) and serum, their concentrations at these sites were examined in ten
      male smokers and 12 male and 10 female non-smokers by fluoro-X-ray analysis. K in
      serum was high, and P, Ca and Fe low, compared to RBC. Mg and S in serum and RBC
      were essentially the same. S, Mg, P and K in RBC of smokers were higher than in
      male non-smokers, and Ca was lower. S and Ca in serum of smokers were
      significantly lower than in male non-smokers. P in smokers was higher than in non
      smokers. P in RBC may possibly activate the reflux of Mg into RBC and may
      suppress that of Ca. In smokers, the correlation coefficient (gamma) between Fe
      and Ca was r = -0.68 in RBC, and r = 0.76 in serum. Also gamma between P and Mg
      was r = 0.4 in RBC and r = -0.48 in serum. Thus Fe in RBC may suppress the reflux
      of Ca. Mg and Ca in serum of females were significantly higher than in male non
      smokers. Ca in RBC of females was significantly higher than in male non-smokers,
      and P, K and Fe were significantly lower. The product of Ca and P in RBC of
      females was lower than in male non-smokers, while in serum it was higher. gamma
      between P and Ca, and between Fe and Ca in RBC of females were negative, while
      they were positive in male non-smokers. The correlations in female RBC had the
      same pattern as in male smokers.

PMID- 9919379
TI  - Does acute exposure to the electromagnetic field emitted by a mobile phone
      influence visual evoked potentials? A pilot study.
AB  - To search for a potential negative influence on the central nervous system (CNS)
      of the electromagnetic field emitted by a mobile phone, the authors performed a
      pilot experimental study of the influence of a single short acute exposure to the
      GSM mobile phone Motorola 8700, using visual evoked potentials (VEP) examination
      as an electrophysiological marker of CNS dysfunction. The study group consisted
      of 20 healthy volunteers. The duration of exposure was 5 minutes. The output
      power of the device was 1.5 W when the antenna was pulled up. Five parameters of
      VEP were evaluated by means of multifactorial ANOVA. Confounding effects of age,
      sex, and of the call in itself were taken into consideration. No statistically
      significant influence of the above-described exposure to the electromagnetic
      field emitted by the mobile phone on latencies or amplitudes of VEP was observed.

PMID- 9919380
TI  - Biological significance of the zoning of the masking effect of noise, related to
      the adaptive capacities of the auditory analyzer for speech communication.
AB  - The paper discusses the problem about the ergonomic assessment of the abilities
      of the auditory analyzer for processing of speech information, depending on the
      zoning of the masking effect of noise and the degree of speech communication. A
      significant increase of the loss of speech information with rise of the
      intensities of the masking effect of noise (from 21.33% at L eq. 40 dB up to 96%
      at L eq. 90 and less than 90 dB/A/) is found. The speech communication is graded
      into 4 bands, depending on the qualitative-quantitative criteria of the processed
      speech communication. The regularity of the standard for masking noise (L eq. 65
      dB/A), which guarantees good comprehensibility is proved from the aspect of
      ensuring the necessary conditions for speech information perception. Equivalent
      levels of masking noise near or equal to L eq. 85 dB/A/ ensure satisfactory
      comprehensibility at the control boards. The abnormal intensities of the masking
      noise effect are of particular importance as they belong to the inadmissible
      (bad) zone of auditory perception of speech information.

PMID- 9919381
TI  - Informativeness of critical ratios "useful signal-masking noise" in speech
      communication.
AB  - In experimental conditions the influence of 8 ratios "useful signal-masking
      noise" of 3 types of production noise (impulse, continuous and interrupted) is
      studied as well as continuous (white) noise as control on the perception of an
      audiometric test by 60 individuals with normal hearing. The test is
      understandable phonetically with difficulties and balanced at speech. The test
      intensity is L(equiv).70-75 dB/A/. The most expressed masking effect of
      continuous (white) noise, followed by the impulse and constant production noise
      is found. The lowest masking effect is found out at interrupted noise. This is
      explained by the acoustic characteristics of exposed types of noise. The masking
      effect of noise is limited to a high degree by the parameter "signal-noise"
      ratio, which is confirmed by the found negative correlation relationship with
      percentage speech intelligibility. The critical ratios "signal-noise",
      characterized with sharp decline of the level of discrimination of speaking
      signal and deterioration of the effectiveness of speech communication are
      established. In this paper the problem for conforming the speech communication
      both with the intensity and acoustic characteristics of masking noise and with
      the "signal-noise" ratio is discussed. Besides this in the critical "useful
      signal-masking noise" ratios better individual achievements could be a criterion
      for professional selection of candidates for operators.

PMID- 9919382
TI  - Qualitative identification of volatile metabolites from two fungi and three
      bacteria species cultivated on two media.
AB  - Two fungal species, Aspergillus fumigatus and Penicillium brevicompactum and
      three bacteria, Klebsiella pneumoniae, Enterobacter agglomerans and Streptomyces
      albus were cultivated on two media, malt extract agar and dichloran glycerol
      agar. The volatile metabolite samples from the cultures were adsorbed on Tenax TA
      and analyzed qualitatively by thermal desorption gas chromatography and with a
      mass selective detector. Various hydrocarbons, alcohols, ketones, esters and
      terpenes were identified. The production was highly dependent on both the medium
      and the microbial species. 2-Methyl-1-propanol, 2-methyl-1-butanol and 3-methyl-1
      butanol were the most commonly produced substances. The bacterial species did not
      produce any hydrocarbons that were characteristic to the fungi (e.g. methyl-1,3
      pentadiene, 1-octene and 1,3-octadiene or 8-carbon alcohols 1-octen-3-ol and 3
      octanol). Instead, K. pneumoniae and E. agglomerans produced 3-hydroxy-2-butanone
      and 1-hydroxy-2-propanone, which were not produced by the fungi. Geosmin and a
      large number of sesquiterpenes were produced by S. albus.

PMID- 9919383
TI  - Comparison of environmental quality in the districts of the Czech Republic with
      mortality pattern and selected health parameters.
AB  - The aim of this study was to analyse a potential connection between the chosen
      parameters of the quality of the environment and the mortality pattern of
      residents in the Czech Republic. By means of linear regression selected
      parameters of the quality of the environment in the districts were compared with
      mortality rates and some other indices of the health status of the inhabitants of
      the districts. The region of Prague was excluded from our study because of a
      substantial gap in environmental data set. The percentage of inhabitants who live
      in an environment evaluated as "acceptable" served as the independent variable.
      The total mortality rate or some other health data were the dependent ones. An
      analysis of our data set has shown that the environment "influences" mortality by
      30% (r2 = 29.6%) in men and even by 40% (r2 = 43.6%) in women. Standardized
      mortality rates by causes of death and some other parameters of the health status
      of the population were also compared with the chosen parameters of the quality of
      the environment. A statistically significant linear association was found between
      the quality of the environment and the standardized mortality rate of malignant
      neoplasm in both men (r2 = 13.8%) and women (r2 = 32.4%), the standardized
      mortality rate of diseases of the circulatory system in women and the incidence
      of TB in men. The highest correlation was found between the quality of the
      environment and the incidence of gonorrhoea (r2 = 51.7%). Apparently this
      dependence is not a causal one. It could be interpreted as a dependence between
      the quality of the environment and the social behaviour of its inhabitants. On
      the verge of significance was male mortality from injury and mortality from
      suicide. No association has been found between the quality of the environment and
      the standardized mortalities from diseases of the respiratory system, the infant
      mortality rate till one year of age, incidence of congenital anomalies and the
      incidence of diabetes mellitus.

PMID- 9919384
TI  - Mutagenicity tests on the bacteria and the detection of genotoxicity of
      industrial complex mixtures containing PAHs.
AB  - The study summarizes the results of an evaluation of mutagenicity of
      heterogeneous complex mixtures of substances, the main mutagenic component of
      which consists of polycyclic aromatic hydrocarbons. The testing was performed
      using bacterial assays of mutagenicity--the SOS chromotest and the S. typhimurium
      His-test (in modifications without and with metabolic activation in vitro). It
      was found that samples of tested tar mixtures (crude tar, pitch, anthracene oils
      III and II, granulated pitch and some of its extraction portions) induced SOS
      repair functions and frameshift mutations in tests with metabolic activation.
      Some of samples as tar, pitch and anthracene oils III, granulated pitch and two
      its extraction portions--LRAC and LRBe--induced also frameshift mutations, and
      SOS repairs in tests without the metabolic activation. In one sample--LRBe--the
      ability to induce mutations in all variants of both tests, was also proved. The
      evaluation of mutagenicity of fly ashes showed that differences in the mutagenic
      activity of samples can be directly dependent on the extraction method chosen and
      on the type of extraction agent used. The study results demonstrate that the
      bacterial tests Salmonella typhimurium His- and the SOS chromotest are
      uninterchangeable and quite independent. Both tests can be used for orientative
      screening for genotoxicity in a wide range of various complex mixtures arising
      from industrial production and contaminating the environment.

PMID- 9919385
TI  - Hygiene aspects of drinking water ultrafiltration.
AB  - Ultrafiltration is highly effective method for removal of bacteria and viruses
      and does not produce organohalides associated with water treatment by chlorine
      gas. The aim was to assess the hygiene suitability of the unit for possible use
      in bottled water production. The ultrafiltration unit was in operation for 220
      hours with simulated of varying duration. The running time (220 hours) and shut
      down duration (to 5 hours) did not in any way influence the effectiveness of the
      module (100% filtration of aerobic colony count at 37 degrees C and 22 degrees
      C).

PMID- 9919386
TI  - Dose-response analysis and biologically-based risk assessment for initiator and
      promoter carcinogens. Summary report of NATO/CCMS Study.

PMID- 9919387
TI  - The UNOS Scientific Renal Transplant Registry--ten years of kidney transplants.
AB  - 1. The number of kidney transplants reported to the UNOS Scientific Renal
      Transplant Registry (excluding multiorgan transplants) increased from 8,831 in
      1988 to 10,204 in 1996, mainly due to increased donation by living donors (1,812
      3,149 during the same period). 2. Overall projected 10-year primary graft
      survival rates were 73% for 3,515 recipients of HLA-identical sibling grafts, 55%
      for 16,160 recipients of other living donor transplants or 3,940 HLA-matched
      cadaveric grafts and 39% for 50,900 recipients of HLA-mismatched cadaver donor
      kidneys. 3. One-year first cadaver graft survival rates improved from 77% in 1988
      to 87% in 1997 and graft half-lives improved from 7.6 years for 1988 transplants
      to 11.6 years for 1994 transplants. 4. Improving graft survival rates were
      associated with a modest 2% increase in one-year patient survival and a projected
      13% increase at 10 years. Better patient survival may contribute to rising long
      term graft survival rates. 5. Immunosuppression has also played an important role
      as the incidence of rejection episodes within the first 6 months decreased from
      52% in 1988 to 24% in 1996 and immunological graft failures declined in 1995 and
      1996 accounting for less than 30% of first year graft losses. The majority of
      first year graft losses were due to patient deaths for the first time in 1995. 6.
      A major change in maintenance immunosuppression occurred in 1996 when about 60%
      of first cadaver transplant recipients received Neoral, MMF and prednisone (NMP)
      at the time of hospital discharge. Preliminary results show a 90% one-year graft
      survival rate with NMP compared with 87% for CsA- and FK-based immunosuppression.
      Improved long-term graft survival that had been previously noted in patients
      treated with FK506 was not apparent in the 1994-96 cohort analyzed. The use of
      induction with OKT3 or ALG reduced rejection episodes during the initial
      transplant hospitalization but did not affect one-year or long-term graft
      survival. 7. There has been a significant improvement in immunological high-risk
      patients. The results of second transplants trailed those of primary grafts by
      only 3% in the 1994-96 period compared with a 6% difference in 1988-90 and
      recently retransplanted patients who were not broadly sensitized had the same
      graft survival rate as unsensitized first transplant recipients. Recipients of
      poorly HLA-matched kidneys also had significantly improved survival rates during
      1994-96. The 3-year survival difference between recipients of kidneys with only
      one or 2 HLA mismatches and those with 5-6 mismatches was 4% compared with 8% for
      comparably matched recipients transplanted in 1988-90. 8. The 3-year graft
      survival rate for Black recipients was 57% in 1988-90 and 67% in 1994-96. The gap
      between Blacks and Whites narrowed from a 9% 2-year survival rate difference in
      the early cohort to 5% in the more recent transplants. Asians transplanted in
      1994-96 had a superior graft survival rate of 90% at one year with an 18-year
      half-life. 9. Despite a substantial increase in the number of living donor
      transplants performed in recent years, graft survival rates were still superior
      to all but the best HLA-matched cadaver transplants. Most of the additional
      living donor activity has involved HLA-mismatched pairs with a 3-fold increase in
      the number of completely HLA-mismatched transplants (513 in 1988-90 vs 1,583 in
      1994-96). The one-year graft survival rates were 96%, 93% and 92% for HLA
      identical, one- and 2-HLA haplotype disparate transplants, respectively.

PMID- 9919388
TI  - Long-term patient and retransplantation-free survival by selected recipient and
      donor characteristics: an update from the Pitt-UNOS Liver Transplant Registry.
AB  - CENTERS: Between 1988 and 1996, the total number of liver transplantations
      performed in the United States more than doubled, and the number of centers
      performing liver transplantations increased from 58 to 106. The yearly net gain
      in number of centers has slowed substantially in recent years, and the reduced
      differences in volume per center reported previously has continued through 1996.
      SURVIVAL AMONG PEDIATRIC RECIPIENTS: The estimated cumulative probability of a
      pediatric recipient surviving for 9 years following transplantation was .71, and
      surviving for 9 years without retransplantation was .58. In general, few deaths
      or retransplantations were observed more than 5 years following the initial
      transplantation. Factors independently associated with patient and
      retransplantation-free survival among children were year of transplantation,
      recipient age, location awaiting transplantation, primary liver disease, pre-LT
      serum creatinine, pre-LT bilirubin, and donor age. Recipient race and multiorgan
      transplantation were significantly associated with patient survival.
      Interestingly, of the 23 multi-organ recipients who survived at least 3 years,
      none died or required retransplantation. SURVIVAL AMONG ADULT RECIPIENTS: The
      estimated cumulative probability of an adult recipient surviving for 9 years
      following transplantation was .55, and surviving for 9 years without
      retransplantation was .48. Though the one-year survival rate among adults was
      slightly better than among children, long-term survival was substantially worse.
      Factors independently associated with patient and retransplantation-free survival
      among adults were year of transplantation, recipient age, race, location awaiting
      transplantation, primary liver disease, pre-LT creatinine, pre-LT albumin,
      recipient HBsAg status, donor age, donor anti-CMV status, ABO match, and sex
      match. Pre-LT bilirubin was significantly associated with patient survival, and
      pre-LT prothrombin time was associated with retransplantation-free survival.

PMID- 9919389
TI  - Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT
      International Registry for thoracic organ transplantation.
AB  - 1. The number of heart transplant operations performed in the United States has
      decreased by 16 procedures between 1995 (2,360) and 1996 (2,344). Following a
      period of rapid growth from 1990 (203) through 1995 (871), there was a decrease
      of 71 lung transplant procedures between 1995 (871) and 1996 (800). 2. The most
      frequently reported indication for heart transplantation in the US was coronary
      artery disease (44.88%). For other thoracic transplants, the most frequently
      reported indications included cystic fibrosis (31.85%) for double lung,
      emphysema/COPD (55.88%) for single lung and congenital heart disease (48.72%) for
      heart-lung transplants. The most frequently reported diagnoses for thoracic
      transplantation outside the US included cardiomyopathy (47.4%) for heart, cystic
      fibrosis (33.0%) for double lung, idiopathic pulmonary fibrosis (29.1%) for
      single lung and primary pulmonary hypertension (23.4%) for heart-lung
      transplants. 3. US heart transplant recipients were predominantly male (77.6%),
      older than age 50 (55.4%) and white (82.3%). In contrast, US lung transplant
      recipients were predominantly female (52.1%), aged 35-64 (73.5%) and white
      (89.5%). No significant variance from the US recipient demographic profile was
      noted for non-US recipients in this analysis. 4. The mean donor age for heart and
      lung transplants has risen slightly with an increase in mean age of 3.12 years
      for heart donors and 4.72 years for lung donors from 1987-1997. 5. The one-year
      survival rate for thoracic transplants performed in the US was 84.8% for heart,
      70.1% for lung and 73.4% for heart-lung in 1996. Five-year survival for US
      thoracic transplants was 66.5% for heart and 43.2% for lung transplants performed
      in 1992. 6. There was little change in heart transplant survival based on
      transplant era (1987-89, 1990-92 and 1993-95). Lung recipients transplanted in
      the 1993-95 era showed a 16% increase in survival compared with those
      transplanted in the 1987-89 era at the 48-month time point. 7. The most important
      risk factor for US heart recipients at one month, one year, and conditionally at
      5 years after transplantation was receipt of a previous heart transplant. Other
      substantial long-term risk factors included donor age and non-white, non-black
      recipient. 8. The most important risk factors for mortality in US lung recipients
      were the order of the transplant (primary or repeat) and the patient's medical
      condition at time of transplant. Diagnosis, recipient age and recipient race were
      highly influential risk factors for conditional 5-year mortality. 9. For heart
      and lung recipients, the major cause of hospitalization during the first 2 years
      after transplantation was infection.

PMID- 9919390
TI  - Pancreas transplants for United States (US) and non-US cases as reported to the
      International Pancreas Transplant Registry (IPTR) and to the United Network for
      Organ Sharing (UNOS).
AB  - As of November 1997 more than 9,800 pancreas transplants had been reported to the
      IPTR, including more than 7,400 US and more than 2,400 non-US cases. Cases
      reported since the inception of UNOS in 1987 (more than 6,800 in the US and more
      than 2,000 from outside the US) were analyzed, with emphasis on 1994-97 cases. In
      the US, for all 1994-97 SPK transplants (n = 2,585), one-year patient, pancreas
      and kidney graft survival rates were 94%, 82% and 90%, respectively; for all PAK
      cases (n = 230), patient and graft survival rates at one year were 95% and 71%;
      and for all PTA cases (n = 117), patient and graft survival rates at one year
      were 93% and 62%, respectively. The 1994-97 pancreas survival rates in all
      categories were significantly higher than in previous eras. Analysis of bladder
      versus enteric drainage (BD vs ED) was made only for 1994-97 SPK cases since
      there were too few solitary ED cases for a comparison. One-year pancreas survival
      rates (all causes of failure included) were 83% for BD (n = 1,995) versus 80% for
      ED (n = 456) cases (p = NS). However, nearly 20% of SPK BD grafts had been
      converted to ED by 2 years. The pancreas retransplant success rates have also
      significantly increased over time. For 1994-97 pancreas retransplants (n = 92),
      the one-year graft survival rate was 72%. The technical failure (TF) rate for
      pancreas transplants has declined over time. For 1994-96 BD cases, the TF rate
      was 8% in SPK (n = 1,995), 13% in PAK (n = 174) and 11% in PTA (n = 90) cases.
      For SPK ED cases (n = 456) the TF rate was 11% (p = 0.06 vs SPK BD). The most
      common cause of technical loss was graft thrombosis, 5.5% for SPK, 10.2% for PAK
      and 6.7% for PTA. The TF rates were significantly higher in grafts from older (>
      45 yrs) donors and donors who died from cardiovascular disease. The immunological
      graft loss rate has also significantly declined in all categories. For 1994-97,
      technically successful (TS) cases (DWFG censored), the rejection loss rate at one
      year was 2% in the SPK (n = 2,234), 9% in the PAK (n = 154), and 16% in the PTA
      (n = 78) categories. Cox multivariate analyses were done in each recipient
      category to assess for factors that influence risks of pancreas graft loss.
      Increasing donor age was a risk factor in all categories. HLA mismatching was
      important only in the solitary (PAK and PTA) categories. FK506 use was associated
      with a positive effect in all categories, as was MMF in the SPK category.

PMID- 9919391
TI  - The UNOS OPTN waiting list and donor registry.
AB  - 1. On October 31, 1997, there were 55,789 registrations on the combined UNOS
      waiting list. Of these, two-thirds were awaiting kidney transplantation, and 17%
      were awaiting liver transplantation. 2. More than one-half of all patients on the
      UNOS waiting list on October 31, 1997 had blood type O, 59% were White, 58% were
      male, and 54% were aged 18-49. 3. Annual additions to the UNOS kidney waiting
      list grew from 11,916 in 1988 to 18,253 in 1996. The largest increase in waiting
      list size was seen in the lung waiting list, which grew 1,482% during this time.
      4. Median waiting times have increased steadily for nearly every organ since
      1988, especially for liver, kidney, and lung registrants. 5. For patients added
      to the waiting list in 1995, MWTs to transplant were longest for heart-lung
      registrants (887 days); however, no median could be calculated for kidney
      registrants added in 1995. The shortest waiting times for this cohort were
      experienced by heart registrants (208 days). 6. Death rates per 1,000 patient
      years at risk have declined during 1988-1996. Death rates were higher for
      patients awaiting life-saving organs (liver, heart, lung, heart-lung) than for
      non-lifesaving organs (kidney, pancreas, kidney-pancreas). 7. There were 5,417
      cadaveric and 3,553 living donors recovered in 1996, a 33% and 95% increase,
      respectively, over those recovered in 1988. 8. The number of organs recovered per
      cadaveric donor increased from 3.0 in 1988 to 3.8 in 1994 and dropped to 3.6 in
      1996. At the same time, the number of organs transplanted per cadaveric donor
      recovered increased from 2.7 to 3.2. 9. Large increases in the number of donors
      who were liver (45-82%), pancreas (14-23%), and lung (3-14%) donors occurred
      between 1988 and 1996. 10. The number of cadaveric donors aged 50 or older has
      increased from 12% of all donors in 1988 to 27% of all donors in 1996. 11. The
      typical cadaveric donor in 1996 was a White male with ABO blood type O, between
      the ages of 18-34. In 1996, a typical living donor was a White female with ABO
      blood type O between the ages of 35-49. 12. Between 1988 and 1996, the percentage
      of minority donations increased for cadaveric donors (17-23%), and for living
      donors (24-27%). 13. The number of living donors who were either spouses or
      unrelated to the recipient increased from 4% in 1988 to 14% in 1996.

PMID- 9919392
TI  - UK National Transplant Database retransplantation in the UK and Republic of
      Ireland, 1987-1996. UKTSSA National Transplant Database.
AB  - At the end of 1996, 1,635 kidney, 17 liver and 24 cardiothoracic recipients were
      registered on the UK and Republic of Ireland national transplant waiting list to
      receive a second or subsequent transplant. These patients represented 20%, 9% and
      4% of the total separate waiting lists, respectively. This clearly demonstrates a
      continuing requirement for retransplantation. A study of the characteristics of
      first and retransplant recipients and their donors shows that retransplant
      recipients tend to be younger and in the case of liver and heart/lung transplants
      are less likely to be male. Survival of liver regrafts is significantly worse
      than first transplant survival. Multifactorial analysis of the factors affecting
      the outcome of kidney retransplants showed outcome to be associated with the
      survival time of the first transplant. In the case of kidney transplantation, the
      younger and the better matched recipients selected for retransplant may at least
      partially explain the comparable one-year transplant survival estimates for first
      and retransplants of 81% and 78%, respectively, for the 1986-1993 dataset of 23
      centers.

PMID- 9919393
TI  - Pediatric renal transplantation--the NAPRTCS experience.
AB  - The NAPRTCS has enrolled 4,329 children who have received an index renal
      transplant since 1987. Seventy-three percent of the transplant recipients were
      children above 6 years of age. In the age group below 6 years rejection episodes
      are not more frequent, however the first acute rejection episode is frequently
      irreversible leading to graft failure. Many of the renal disorders that lead to
      ESRD and transplantation in adults, such as diabetes and hypertension, are less
      often observed in the pediatric population. Developmental disorders, such as
      renal dysplasia and obstructive uropathy, are frequent diagnostic entities, and
      the most common glomerular disorder leading to transplantation in children is
      focal segmental glomerulosclerosis. In an attempt to overcome dialysis-associated
      growth retardation many pediatric renal centers resort to preemptive
      transplantation, thus 24% of the children receiving a transplant have never
      undergone dialysis. Graft survival in these children is similar to that observed
      in children receiving maintenance dialysis, however accelerated growth is not
      noted. Catch-up growth, defined as gain of 1 SDS, is observed in 47% of children
      below the age of 6 years and in only 22% of children over the age of 6 years.
      Infants (below 2 years) have a higher mortality rate following transplantation
      compared to older children. Long-term (5-year) graft survival for children
      receiving a cadaver donor graft is 60%, and for living donor kidney recipients
      the graft survival is 76%. Due to changes in practice patterns, such as a
      judicious use of cadaver donors, increased use of prophylactic T-cell antibody,
      and better maintenance immunosuppression, cadaver donor graft survival has
      improved each year since 1987. The cohorts of children with a cadaver donor
      transplant in the years 1991 and 1992 have a 2-year graft survival which is 10%
      better than that observed in the earlier years.

PMID- 9919394
TI  - Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of
      pregnancy after transplantation.
AB  - Female solid organ recipients with good graft function generally tolerate
      pregnancy well. However, the combination of mother, fetus, transplanted organ,
      and immunosuppressive and other medications increases the complexity of
      management and raises the specter of adverse outcomes. For the mother,
      considerations include the nature of the original disease (i.e. genetic risk of
      transmission), co-morbid conditions which increase pregnancy risk (i.e.
      hypertension, diabetes, renal insufficiency), and long-term maternal prognosis.
      For the fetus, questions include the adequacy of maternal physiology (cardiac,
      renal, glycernic control, etc.), exposure to medications, and exposure to
      infectious agents. The transplanted organ must accommodate the increased workload
      of pregnancy and the needs of the fetus. The delicate balance between
      immunosuppression and rejection may be altered by the pregnancy. The impact of
      pregnancy on recurrent disease can also be an issue. Medication issues include
      changes in drug pharmacokinetics and the potential for adverse effects on the
      fetus. These effects could include chromosomal aberrations, structural
      malformations, organ-specific toxicity, intrauterine growth retardation, and
      immune system development. For female kidney recipients there are sufficient data
      to demonstrate a direct relationship between creatinine levels before and during
      pregnancy and risk of graft loss in the postpartum period. Pregnancy itself does
      not appear to adversely affect stable graft function. Among liver recipients,
      those with recurrent viral hepatitis may have deterioration of graft function
      with subsequent pregnancies. These recipients should be apprised accordingly, as
      maternal deaths have occurred in this setting. Postpartum depression and
      potential for medication noncompliance require vigilance. The safety of pregnancy
      from the NTPR analysis to date has been largely derived from the experience with
      CsA-based regimens. For recipients on CsA there have been good maternal outcomes
      without any specific or predominant malformation patterns in the offspring. For
      the general population, malformations occur in approximately 3% of live births.
      To date, there is no indication that this incidence has increased despite the
      complex medical regimens of transplant recipients. Data are accruing with
      tacrolimus and Neoral. Continuing data entry and continued follow-up of off
      spring will allow for further recommendations, especially in light of the new
      medications and combinations. Recipients should be advised to wait one to 2 years
      after transplant before considering pregnancy. Those with stable graft function,
      and with no rejection, graft dysfunction, or deterioration should still be
      apprised of the high risk of prematurity and low birthweight, although maternal
      risks appear low. These are high-risk pregnancies, requiring close communication
      and cooperation between the high-risk obstetrician and the transplant team. The
      use of the FDA pregnancy categories should not be the sole reason for choosing a
      particular immunosuppressive drug. Agents such as Neoral and tacrolimus would
      appear to offer some advantage as blood levels can be measured. At present, no
      safety guidelines can be given for mycophenolate mofetil, OKT3, or ATG.
      Identification of prepregnancy factors predictive of higher risks and appropriate
      counseling and management guidelines are major NTPR goals, and depend on the
      continued assistance and cooperation of the transplant community.

PMID- 9919395
TI  - Kidney transplantation at UCLA--the past 10 years.

PMID- 9919396
TI  - Long-term results and complications of renal transplantation: the Hennepin
      experience.
AB  - Approximately one sixth of patients receiving renal transplants have a
      functioning kidney beyond 20 years. Chronic rejection is the predominant cause of
      late allograft loss. Malignancy, cardiovascular disease, hepatic failure, and
      infections are the major causes of late death. Early detection and control of the
      risk factors that contribute to patient death should favorably influence the long
      term success of renal transplantation.

PMID- 9919397
TI  - Factors influencing kidney transplantation in Manchester, UK: 1989-1996.
AB  - The Manchester renal transplant center has the highest single center activity in
      the UK at present and has managed to achieve high posttransplant survival rates.
      We believe that this success is due to a combination of factors including a
      conservative approach to patient management; changes in clinical practice are
      only made after the evidence base has been established. This center is committed
      to the philosophy of prolonged survival of all transplanted kidneys. We believe
      that transplanting kidneys into clinically high-risk patients is not the best use
      of available resources.

PMID- 9919398
TI  - Kidney and kidney/pancreas transplantation at Stanford University Medical Center.
AB  - The disparity between the supply of cadaveric donors and the demand for renal
      allografts continues to grow. We have taken a multifaceted approach to increase
      the allograft pool: 1. Spiral computed tomography to evaluate potential living
      kidney donors is safer, less invasive, less expensive and more time efficient and
      thus should encourage living organ donation. 2. Use of selected expanded criteria
      cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched
      recipients have short-term function at 3 and 6 months comparable to standard
      cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59
      and with an adjusted creatinine clearance less than 90 ml/min should be used as a
      dual kidney transplant into an appropriate sized- and aged-matched recipient. 4.
      Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc
      grafts, when transplanted into adult recipients. Pediatric renal transplantation
      poses numerous challenges given the different and problematic etiologies of ESRD,
      the surgical considerations in small children and infants and the enhanced immune
      response witnessed in children. Nevertheless, renal transplantation is clearly
      the therapy of choice for children with ESRD and excellent results can be
      obtained through strict adherence to surgical detail, tight immunosuppressive
      management, and aggressive fluid management in infants and small children. We
      feel it is also critically important that transplantation and follow-up care be
      carried out by an integrated and experienced surgical and medical team. Managed
      healthcare has had profound effects on the practice and management of
      transplantation centers. The one area of greatest impact has been the pressure
      upon programs to reduce their cost of transplantation. We have initiated a number
      of new outpatient treatment protocols as part of an effort to contain costs. Most
      patients with acute rejection are evaluated (including transplant kidney biopsy)
      and treated in an ambulatory setting. Completion of OKT3 therapy in selected
      patients is also performed at home through visiting nurses or at our ambulatory
      care center. Additionally, treatment of CMV disease is now performed almost
      exclusively on an outpatient basis.

PMID- 9919399
TI  - Results of kidney transplantation from 1979 to 1997 at Yonsei University.
AB  - 1. Long-term graft survival markedly improved after the introduction of CsA as
      the main immunosuppressant in living-donor kidney transplantation at our
      institution. 2. HLA-identical LRD kidney transplantation provided the best long
      term graft survival rate, probably due to a decreased incidence of graft loss
      from rejection. 3. We could achieve good long-term graft survival in LURD kidney
      transplantation compared with that of HLA-haploidentical LRD kidney
      transplantation. 4. Because of the striking discrepancy between organ donation
      and the increasing demand for transplantation, distant relative donors and LURDs,
      including swap donors, should be considered as an alternative way to increase the
      number of available donors when accompanied by a careful evaluation process.

PMID- 9919400
TI  - Advances in pancreas transplantation: the University of Wisconsin experience.
AB  - The data show that with careful surgical technique, modern immunosuppression with
      MMF and FK506, and pancreatic allograft biopsy, it should be possible to achieve:
      1) a low rate of technical complications, 2) improved long-term graft survival,
      particularly in solitary pancreas recipients improving the risk/benefit ratio of
      this option for nonuremic diabetics, 3) a high safety profile with combined MMF
      and FK506 immunosuppression, 4) safe transplantation using enteric drainage
      without increased risk of rejection, infection or graft loss, and 5) successful
      pancreas transplantation without induction therapy.

PMID- 9919402
TI  - Twelve years of liver transplantation at the Mayo Clinic.
AB  - During the past 12 years, the Mayo Clinic Liver Transplant Program has continued
      to flourish. Not only has the program steadily grown in the numbers of patients
      transplanted, but now we are achieving an overall 90% one-year survival rate and
      have reduced our median posttransplant hospital stay to 9 days. Furthermore, a
      protocolized approach to the procedure has allowed us to continuously evaluate
      the appropriate use of resources and has allowed us to decrease the use of
      certain laboratory tests, reduce the use of radiologic and invasive procedures,
      and improve the overall cost efficiency. The challenge of the future will be to
      deal with recurrent disease and retransplantation. We desperately need treatment
      to prevent the recurrence of hepatitis B and C and, finally, we continue to
      search for immunosuppressive therapies that are less toxic and less costly.

PMID- 9919401
TI  - Simultaneous pancreas-kidney transplantation at the Ohio State University Medical
      Center.
AB  - Simultaneous pancreas-kidney transplantation is possible in a large number of
      Type I diabetics with excellent patient and graft survival. Diabetic patients are
      prone to coronary artery disease (CAD) which remains the most common cause of
      death in both the pre- and posttransplant periods. Exclusion of significant CAD
      and/or cardiac dysfunction in the potential recipient is necessary. At The Ohio
      State University, one-year patient, pancreas and kidney graft survival rates were
      92%, 80%, and 84%, respectively. Acute rejection following simultaneous pancreas
      kidney transplantation remains a major problem but has been positively affected
      by newer agents. Enteric conversion is needed in less than 10% of the patients
      over a period of 53 months. Prospective studies comparing primary enteric
      drainage and bladder drainage are needed to determine the best technique, as well
      as immunosuppressive regimens.

PMID- 9919403
TI  - The Hamburg liver transplant program.
AB  - The program of the University of Hamburg is exemplary of the problems faced by
      programs with rapid growth. Establishing expertise at all levels is essential to
      shorten the inevitable learning curve. The combination of an adult and a
      pediatric program was an ideal environment for the development of living donation
      and cadaveric in-situ split liver transplantation as complimentary solutions to
      eliminate pediatric mortality on the waiting list without affecting the chances
      of adult liver transplant candidates.

PMID- 9919404
TI  - Living-donor liver transplantation in Kyoto, 1997.
AB  - Although a new law allowing for organ retrieval from brain-dead donors was
      recently put into force, living donors remain the major source for liver
      transplantation in Japan. The number of LDLT cases in Kyoto University has
      increased yearly, reaching 336 transplantations in 329 patients in November 1997.
      Because the program has expanded without support from cadaveric organ sources, we
      have been confronted with difficulties with graft size mismatches, major ABO
      blood group incompatibilities and highly deteriorated emergency cases. Despite
      innovations in surgical techniques which have reduced vascular complications, and
      several immunomodulations to mitigate complications of mismatched blood groups,
      graft survival in these cases remains approximately 20% lower than that for less
      complicated transplants. This report summarizes our recent struggles with these
      problems and some of our solutions.

PMID- 9919405
TI  - Cardiac transplantation: the University of Florida experience.
AB  - Heart transplantation offered satisfactory outcomes in carefully selected
      patients with end stage congestive heart failure treated at our institution from
      1990-1996. At the University of Florida, our survival rates involving 196 heart
      transplants were 86%, 78% and 74%, respectively, at one, 3 and 5 years. This data
      compares favorably with international results. Our typical transplant recipient
      was a 50-60 year old caucasian male with ischemic cardiomyopathy. Based on this
      population and the severe shortage of donor hearts available, aggressive attempts
      must continue to identify patients with ischemic cardiomyopathy that may benefit
      (i.e. adequate target vessel, viable myocardium) from high-risk coronary artery
      bypass surgery. Infection, rejection and graft vasculopathy continue to influence
      morbidity and mortality after transplantation. Continued efforts aimed at the
      development of improved immunosuppression as well as prevention and containment
      of coronary vasculopathy are needed if these results are to be significantly
      improved.

PMID- 9919406
TI  - Lung and heart-lung transplantation at the University of Pittsburgh.
AB  - The application of lung transplantation as a treatment modality for patients with
      severe pulmonary disease has changed dramatically since its inception. At the
      University of Pittsburgh, the criteria for recipient selection continues to
      evolve and, in an effort to maximize scarce donor organs, the criteria for donor
      lung acceptance have been extended. Patient survival during the first 3 years
      after transplantation continues to improve but longer term survival is limited by
      infectious complications and chronic rejection. In early studies, the utilization
      of cyclosporine delivered directly to the lungs via aerosol has resulted in
      dramatic improvement in pulmonary function in recipients with immune mediated
      allograft injury and has allowed a reduction in systemic immunosuppression. We
      are hopeful that interventions such as this will result in prolongation of
      patient survival with less toxicity.

PMID- 9919407
TI  - Determinants of familial consent to organ donation in the hospital setting.
AB  - More than half of the nation's donor potential is lost due either to failure to
      identify medically suitable potential donors, or to family refusal to donate.
      While family consent rates typically average around 50% we show that these rates
      can be substantially improved by incorporating a few simple request process
      elements that are designed to meet the needs of grieving families. If relevant
      critical care and OPO staff are trained and empowered to carry out high-quality
      request procedures, consent rates, and donation overall can increase
      substantially.

PMID- 9919408
TI  - Living kidney donation: donor risks and quality of life.
AB  - This review describes the immediate and long-term risks to kidney donors. We
      reviewed their perioperative morbidity and mortality as well as their quality of
      life after donation. The overall mortality in our series was zero. Nationally,
      donor mortality has been estimated to be 0.03% (5). Our overall complication rate
      was 8.2% with only 2 (0.2%) complications considered to be major (16).
      Complications were associated with male sex, body weight > or = 100 kg, and
      inadvertent entry into the pleura during the donor operation. Most of our donors
      were discharged from the hospital in < 5 days. Risk factors for a longer hospital
      stay were age 50 or older and an operative time of 4 hours or more. The average
      donor quality of life after donation, as measured by the SF-36, was better than
      that of the general US population. This finding persisted for years after
      donation. The vast majority of our donors found the experience to be very
      rewarding and would readily donate again if it were possible. However, 4% were
      dissatisfied and regretted their decision to donate a kidney; these were most
      likely to be donors other than a first-degree relative and donors whose recipient
      died within the first posttransplant year. Living donation of kidneys appears to
      be relatively safe, with very few physical and psychologic complications. It may
      even improve the donor's quality of life. Living donors are an underutilized
      source of kidneys. We continue to advocate and encourage living kidney donation.

PMID- 9919409
TI  - Update in transplantation--1997.

PMID- 9919410
TI  - Strategy for eliminating the kidney shortage.
AB  - 1. We anticipate that the number of kidneys from conventional heart beating
      donors who are under age 55 will remain stable at about 8,000/year. A natural
      increase of donors over age 55 and living donors is expected to increase the
      total transplants from about 12,000 today to 14,000 in 8 years. 2. We propose a 4
      year acceleration phase, during which older cadaver donors, related and unrelated
      living donors will be increased to a maximum of 4,000 in the 4th year. This
      acceleration is a temporary one, and will be reduced to zero over 4 subsequent
      years. 3. An increase in NHBD will be encouraged at a rate of 700/year, so that
      at the end of 14 years, they would constitute about 10,000 cadaver donor kidneys.
      As can be seen in Figure 1, at this rate, NHBD kidneys will first replace the
      accelerated effort, then replace the living donors and eventually the older heart
      beating donors. With the abundance of kidneys, it is likely that many patients
      who are not listed today would be encouraged to become transplant candidates.
      Moreover, patients needing retransplants will increase. However, once this
      capacity is developed, any increases in new transplant candidates could be
      accommodated. Thus in 14 years, there will be about 18,000 kidneys available each
      year. Approximately 60% will be NHBD and 40% heart beating donors, with no living
      donors and no older donors and no need of pig donors. We will be in transplant
      nirvana.

PMID- 9919411
TI  - Spousal and other living renal donor transplants.
AB  - Aside from HLA identical sibling donors, spousal donor transplants are the best
      living donors because their 3-year graft survival is comparable to that of all
      other living donors--with the exception of HLA identical siblings. Interestingly,
      the 14.5 year half-life of spousal donor kidneys was superior to the 10.8 year
      half-life of other living donor transplants. Better quality kidneys is the
      principal explanation for higher spousal donor graft survival rates when compared
      with cadaver donors. This was evident from the 2% anuria rate in the first post
      operative day for spouse donor compared with 10% of cadaver donor transplants.
      Moreover, the requirement for dialysis was 6% for spouse donor grafts compared
      with 22% of cadaver donor transplants. The damage is not attributable to cold
      ischemia time but rather to agonal events and shock prior to kidney harvesting.
      In a survey of 176 spousal renal transplant donors, 175 of 176 said they would
      advise others to donate a kidney to a spouse--and only one donor advised against
      it. Of the "yes" responses, 28% provided additional comments enthusiastically
      recommending it. About 47% reported improvements in the marital relationship, 29%
      in the sexual relationship, and 25% described improved relations with their
      children. The fact that the donor reaps many direct personal benefits should make
      spousal donation the first consideration for living-donation (after the HLA
      identical sibling donor).

PMID- 9919413
TI  - Effect of delayed graft function on short- and long-term kidney graft survival.
AB  - Delayed graft function (DGF) has been identified as a predictor of poor long-term
      graft survival, but whether its effects are independent of rejection or final
      serum creatinine level is controversial. Based on the results of 57,025 first
      cadaver transplants reported to the UNOS Registry, we showed that: 1. Early acute
      rejection significantly lowered one-year graft survival rates by 8-9% in kidneys
      with early function (EF) (89% vs 80%; p < 0.001) or with DGF (72% vs 64%; p <
      0.001). 2. DGF significantly lowered short- and long-term graft survival in
      patients without rejection (EF-1-yr graft survival rate of 89%, t1/2 of 9.5 years
      vs DGF-72% 1-yr graft survival rate, t1/2 of 6.7 years; p < 0.001). 3. Even when
      the discharge serum creatinine level was < 2.0 mg/dl with no rejection, DGF
      lowered graft survival (EF-1-yr graft survival rate of 93%, t1/2 of 10.4 years vs
      DGF-90% 1-yr graft survival rate, t1/2 of 7.6 years; p < 0.001). 4. Acute
      rejection, elevated discharge serum creatinine level (2-6 mg/dl) and older donor
      age (46-60 yrs) each lowered one-year graft survival rates in a stepwise fashion.
      There was exceptionally poor graft survival of kidneys from donors aged 46-60
      with DGF, whether or not early acute rejection was present (with rejection-1-yr
      graft survival rate of 61%, t1/2 of 5.6 yrs vs no rejection-1-yr graft survival
      rate of 71%, t1/2 of 5.3 yrs). 5. Increasing cold ischemia time only decreased
      graft survival when there was no DGF and no rejection and had no significant
      effect on long-term graft survival. 6. Among recipients of HLA-matched cadaver
      kidneys, DGF lowered short- and long-term graft survival, even in the absence of
      early rejection (EF-1-yr graft survival rate of 93%, t1/2 of 14.8 yrs vs DGF-1-yr
      graft survival rate of 76%, t1/2 of 7.8 yrs). 7. DGF was associated with higher
      rates of acute rejection but impaired long-term graft survival even when
      rejection was absent and discharge creatinine was normal. These data support the
      hypothesis that DGF leads to an injury response that can reduce graft survival
      through antigen dependent and antigen independent mechanisms.

PMID- 9919412
TI  - Clinical aspects of sensitization.
AB  - 1. The incidence of broad sensitization has decreased significantly over the past
      8 years, probably due to a decrease in pretransplant blood transfusions. Graft
      survival rates among broadly sensitized patients have improved over this time
      period (76% graft survival at 2 years posttransplant for patients transplanted in
      1995-1996 compared with 66% for patients transplanted in 1989-1990). This is
      probably due to an improvement in immunosuppression and a related decrease in the
      incidence of acute rejection episodes. 2. As has been shown before, blood
      transfusions, previous pregnancies and failed allografts independently increased
      the incidence of sensitization. It is clear that certain subgroups of patients
      are more likely to become sensitized, given antigenic stimulation, as evidenced,
      for example, by the fact that 52% of patients receiving more than 10 units of
      blood prior to transplant were relatively unsensitized. Males seem to be less apt
      than nulliparous females to become broadly sensitized, although this may be due
      to the lower age of nulliparous females. Asians are the least likely race to
      become broadly sensitized. Among multiparous Asians who received more than 5
      units of blood, 27% were broadly sensitized compared with 35% of comparable
      Whites and African Americans. 3. The incidence of acute rejection episodes
      increased with increasing degrees of sensitization. About 46% of first cadaveric
      allograft recipients with PRA levels greater than 50% had at least one acute
      rejection episode within 6 months after transplantation compared with 38% of
      unsensitized individuals. In addition, sensitized individuals were more likely to
      have an episode of early acute rejection before discharge from the hospital. 4.
      Induction with antilymphocyte antibody preparation was more commonly used in
      broadly sensitized patients. However, this therapeutic modality did not reduce
      the incidence of rejection episodes measured at 6 months posttransplant. In
      addition, the use of induction therapy for broadly sensitized patients has
      decreased with the advent of newer immunosuppressive protocols that include
      Neoral, MMF and FK506. 5. There was an association between the incidence of broad
      sensitization and delayed graft function. Induction therapy was more commonly
      used in patients with both delayed graft function and broad sensitization,
      although the decision to use this therapeutic modality seems to be made based on
      the presence of broad sensitization rather than the presence of delayed graft
      function. 6. Choosing the optimal immunosuppressive drug regimen is an important
      decision in broadly sensitized individuals because of the increase in acute
      rejections and decrease in overall graft survival in this group. Classic teaching
      suggests that this group of patients should be administered induction therapy
      with antilymphocyte antibody preparations. Early data suggests, however, that the
      combination of Neoral, mycophenolate and prednisone may be the optimal regimen
      for these individuals with respect to graft survival and that the addition of
      antibody induction therapy to any of the other commonly used regimens does not
      improve graft survival (at least up to 3 years after transplantation).

PMID- 9919414
TI  - Impact of new variables reported to the UNOS registry.
AB  - 1. Donor age is now a predominant factor influencing graft outcome. 2. A new
      finding here is that recipient peripheral vascular disease, PVD is also a major
      factor. This factor was independent of whether the patient had diabetes or not.
      Presensitization, as shown by a high PRA is additive to PVD. 3. Hypertension in
      the donor was important only when a history of more than 10 years was noted in
      the older donors over age 50. 4. Angina and cardiovascular disease in the patient
      resulted in a slightly higher death rate, but was only of importance in patients
      over age 50. 5. Cadaver donor pretreatment was of importance only in donors over
      age 30. 6. White patients with private insurance had a slightly higher graft
      survival rate than those on Medicare or Medicaid. Black patients with private
      insurance had almost the same graft survival as White patients with private
      insurance. The lowest graft survival was noted for Black patients on Medicaid.

PMID- 9919415
TI  - Class I peptides involved in the indirect pathway of allorecognition.
AB  - 1. Donor HLA class I peptides that best "fit" the recipient's HLA-class II
      antigen peptide motifs were determined as peptide scores. 2. Transplants with
      high-scoring donor peptide mismatches had reduced long-term outcome. 3. Peptides
      identified in this analysis may be useful for induction of tolerance, diagnosis
      of rejection, and improvement in allocation of more histocompatible kidneys.

PMID- 9919416
TI  - Look-up survival tables for renal transplantation.

PMID- 9919417
TI  - Secondary prevention in the elderly.

PMID- 9919418
TI  - Hypertension in the elderly: management issues.

PMID- 9919419
TI  - High plasma homocysteine: a risk factor for vascular disease in the elderly.
AB  - Homocysteine is an intermediate compound formed during the metabolism of
      methionine. Several studies have shown that plasma homocysteine concentrations
      rise with age. Overt or borderline deficiencies of folate, vitamin B12 or B6 and
      possibly age-related kidney dysfunction are the major causes of homocysteine
      elevation in the elderly population. Multiple case-control and prospective
      studies have shown that a high plasma homocysteine concentration is an
      independent risk factor for cardiovascular diseases; this association persists in
      the elderly. Supplementation with folic acid either alone or with vitamins B12
      and B6 can lower plasma homocysteine. Intervention studies to assess the effects
      (if any) of such treatment on prognosis are now in progress in patients with
      vascular disease.

PMID- 9919420
TI  - Comprehensive cardiovascular disease risk reduction in the clinical setting.

PMID- 9919421
TI  - Expression of intercellular adhesion molecule-1 in human coronary endothelial and
      smooth muscle cells after stimulation with tumor necrosis factor-alpha.
AB  - BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) is one of several
      human cell adhesion molecules that play a critical role in the early stages of
      postangioplasty restenosis. In this study, the in-vitro expression of ICAM-1 in
      human coronary endothelial cells and human coronary smooth muscle cells (SMC)
      after stimulation with tumor necrosis factor-alpha (TNF-alpha) was investigated.
      METHODS AND RESULTS: SMC were isolated from the media of normal human coronary
      arteries (n = 26) up to 10 h post mortem (HCMSMC) and from human atherosclerotic
      coronary arteries (HCPSMC) that were extracted by thrombendarterectomy (n = 25).
      Endothelial cells of human coronary arteries (HCAEC) were purchased from
      Clonetics (Cell System, Remagen, Germany), and endothelial cells from human
      umbilical cord veins (HUVEC) were isolated after vaginal delivery. For
      investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the
      proliferative activity of HUVEC, HCAEC, HCPSMC, and HCMSMC, serum-free media was
      used. After 24 h cell number and cell size distribution were measured in a cell
      analyzer system. The proliferation of HCPSMC and HCMSMC was increased by TNF
      alpha; however, significant differences compared with controls were not reached.
      The proliferation of HUVEC and HCAEC was significantly reduced by TNF-alpha. For
      investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the
      surface expression of ICAM-1, monoclonal anti-ICAM-1 antibodies (84H10) were
      used. The expression of ICAM-1 was analyzed using an immunofluorescence
      microscope. For flow cytometry analysis, 5 x 10(3) cells (100% gated) were
      analyzed using a fluorescence-activated cell sorter. In control cultures with no
      stimulation, the expression of ICAM-1 was positive in HCAEC, HCPSMC, HCMSMC, and
      HUVEC. TNF-alpha stimulated the expression of ICAM-1 in a time- and dose
      dependent manner. After maximal stimulation with TNF-alpha (20 ng/ml for 24 h),
      the expression of ICAM-1 was stronger in HCMSMC than in HCPSMC. CONCLUSIONS:
      These results suggest that the cytokine TNF-alpha regulates the expression of
      ICAM-1 in both human coronary endothelial cells and SMC, and could therefore play
      an important role in the pathophysiology of inflammatory and immune processes in
      restenosis after angioplasty.

PMID- 9919422
TI  - The clinical course of patients with acute myocardial infarction who are
      unsuitable for thrombolytic therapy because of the presenting electrocardiogram.
      UK Heart Attack Study Investigators.
AB  - OBJECTIVE: To examine the clinical characteristics and 30-day fatality rate among
      patients with electrocardiograms (ECGs) ineligible for fibrinolysis in a
      consecutive series in four general hospitals in the UK. METHODS: We studied 2439
      consecutive patients who were identified from regular ward visits, surveillance
      of results from hospital laboratories, and hospital discharge coding. RESULTS:
      Thirty percent (732) of patients did not have ECGs eligible for fibrinolysis
      therapy, while indications were uncertain in 55 (2%). Within the ineligible
      group, patients presenting with ST depression (n = 294) had a higher 30-day
      fatality rate than those with ST elevation or left bundle branch block (26%
      versus 17%; P < 0.001); they represented 40% of the group ineligible for
      fibrinolysis therapy, or 12% of the total cohort. Thirty-day fatality rates in
      patients presenting with pathological Q waves and no diagnostic ST segment
      changes (n = 130), those with T wave changes but no other abnormality (n = 168)
      and those with a normal ECG (n = 128) were 10%, 5% and 3%, respectively. Despite
      their high fatality rate, fewer patients with ST depression were admitted to
      coronary care units than those with ECGs eligible for fibrinolysis therapy (61%
      versus 85%; P < 0.001) and 23% did not receive heparin. The coronary anatomy in a
      subset of patients with ST depression showed two- or three-vessel disease in 79%
      and left main stenosis in 9%. The rates of coronary revascularisation were low in
      all groups (< 10%). CONCLUSION: Patients with ECGs ineligible for fibrinolysis
      therapy are a disparate group, with a high rate of fatality occurring in patients
      who present with ST depression. The high prevalence of multiple vessel coronary
      disease in patients with ST depression suggests that a more active management
      strategy is required.

PMID- 9919423
TI  - Acute myocardial infarction: are there missed opportunities for reperfusion? UK
      Heart Attack Study Investigators.
AB  - AIMS: To investigate the current use of thrombolytic therapy in the management of
      patients with acute myocardial infarction and to determine the potential for an
      increased use of thrombolysis or percutaneous transluminal coronary angioplasty
      (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial
      infarction were identified in three health districts in the UK (population of
      960,000) in patients under the age of 76 years during a 2-year period; 2439
      patients had acute myocardial infarction, of whom 1264 (52%) received
      thrombolytic therapy. Failure to administer thrombolytic therapy was a result of
      the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late
      presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a
      bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%)
      patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as
      a contra-indication could, in retrospect, have received thrombolytic therapy and
      a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The
      potential for increasing the use of thrombolytic therapy seems to be limited and
      is unlikely to make a major impact on the in-hospital mortality from acute
      myocardial infarction. However, primary PTCA should be considered in those who
      are ineligible for thrombolysis because of bleeding risk as a contra-indication.

PMID- 9919424
TI  - Dietary soy isoflavones inhibit in-vivo constrictor responses of coronary
      arteries to collagen-induced platelet activation.
AB  - BACKGROUND: Soy isoflavones (particularly genistein) improve impaired
      acetylcholine-induced dilator responses of atherosclerotic coronary arteries.
      Genistein reduces platelet accumulation of serotonin, whose constrictor
      properties are augmented by dyslipoproteinemia and atherosclerosis. Studies were
      therefore designed to examine the effects of soy protein (with and without the
      isoflavones) on platelet-induced constrictor responses of coronary arteries of
      primates. METHODS: Twelve adult female rhesus monkeys were fed for 6 months an
      atherogenic diet identical in composition, except that isoflavones were either
      extracted with alcohol [n = 6, Soy(-)] or left intact (n = 6, Soy(+)]. Vasomotor
      responses were assessed in vivo using quantitative coronary angiography and
      intravascular Doppler measurements of blood flow velocity. RESULTS: As shown
      previously, soy isoflavones improve impaired dilator responses to acetylcholine.
      Furthermore, in response to activation of platelets by intracoronary infusion of
      collagen, reductions in blood flow through the left circumflex coronary artery,
      but not large artery constriction, were less in the Soy(+) (10 +/- 5%) than in
      the Soy (-) monkeys (35 +/- 6%, P = 0.02). In-vitro platelet aggregation to
      thrombin and serotonin were less in the Soy(+) than in the Soy(-) monkeys (P <
      0.05). However, soy diets did not affect vascular reactivity properties of large
      artery or resistance size arteries to adenosine diphosphate (ADP), nitroglycerin,
      or serotonin (P > 0.05). CONCLUSIONS: We conclude that components of the soy
      protein removed by alcohol extraction (probably the isoflavones) promoted
      endothelium-modulated dilation and inhibited constrictor responses to collagen
      infusion by inhibiting platelet aggregation or platelet release of
      vasoconstrictors, or both.

PMID- 9919425
TI  - Exercise training in elderly patients with chronic heart failure.
AB  - BACKGROUND: Physical training currently constitutes an important part of
      treatment of heart failure patients. So far, no data are available on the effects
      of regular exercise in elderly (aged > 65 years) heart failure patients. METHODS:
      In a prospective trial, patients with chronic heart failure (New York Heart
      Association class II and III) were randomly assigned to a training group and a
      control group. Patients in the training group performed additional exercises
      three times a week, while patients in the control group continued regular
      treatment. To analyse the influence of age, both groups were subdivided into
      subjects younger than and older than 65 years. The effect of training on exercise
      parameters was evaluated by means of a treadmill test. Quality of life aspects
      were evaluated with the help of the Heart Patients Psychological Questionnaire
      and a single-question Self Awareness of General Well-Being test. RESULTS:
      Comparison of changes between groups revealed that training increased the
      duration of the exercise test and improved aspects of quality of life in the
      trained patients aged both younger than and older than 65 years. CONCLUSION:
      Exercise training is equally effective in patients aged younger than and older
      than 65 years.

PMID- 9919426
TI  - Bibliography current world literature.

PMID- 9919427
TI  - Childhood obesity.
AB  - Approximately 10% of children are obese. Twin and adoption studies demonstrate a
      large genetic component to obesity, especially in adults. However, the increasing
      prevalence of obesity over the last 20 years can only be explained by
      environmental factors. In most obese individuals, no measurable differences in
      metabolism can be detected. Few children engage in regular physical activity.
      Obese children and adults uniformly underreport the amount of food they eat.
      Obesity is particularly related to increased consumption of high-fat foods. BMI
      is a quick and easy way to screen for childhood obesity. Treating childhood
      obesity relies on positive family support and lifestyle changes involving the
      whole family. Food preferences are influenced early by parental eating habits,
      and when developed in childhood, they tend to remain fairly constant into
      adulthood. Children learn to be active or inactive from their parents. In
      addition, physical activity (or more commonly, physical inactivity) habits that
      are established in childhood tend to persist into adulthood. Weight loss is
      usually followed by changes in appetite and metabolism, predisposing individuals
      to regain their weight. However, when the right family dynamics exist--a
      motivated child with supportive parents--long-term success is possible.

PMID- 9919428
TI  - Commentary: is maternal stimulation the mediator of the handling effect in
      infancy?
AB  - In a recent report, a series of studies is described showing that individual
      differences in rat maternal licking and grooming are correlated with their
      offsprings' later adrenal response to a stressor (Liu et al., 1997). Pups that
      received more maternal stimulation in infancy had lower ACTH, corticosterone, and
      CRH mRNA, while they had greater amounts of GR mRNA. Liu et al. also compared
      maternal behavior in litters where rat pups were handled daily to maternal
      behavior of nonhandled litters. They found that mothers of handled pups licked
      and groomed their young significantly more often than did mothers of control
      litters. In their discussion, Liu et al. proposed that their data support
      Levine's (1975) thesis that handling effects in infancy are mediated via the
      mother. Levine had proposed that handling of pups will modify the mother--pup
      interaction, thereby causing a change in maternal behavior. The purpose of this
      commentary is to summarize data obtained with mice and rabbits which, in part,
      support and, in part, challenge the conclusions of Liu et al.

PMID- 9919429
TI  - Voltage associated with spontaneous embryonic motility in the developing chicken:
      an automated characterization during mid-late embryogenesis.
AB  - Movement of developing chicken embryos and their associated membranes generates
      voltage detectable with electrodes inserted just beneath the eggshell. Use of
      such voltages as a motility indicator offers an embryonic behavioral assessment
      method less subjective and invasive than observational methods using windows that
      disrupt substantial portions of the eggshell. We used a computerized signal
      recording and processing procedure to compare voltages from embryonic Day 12
      (E12), E15, and E18 chicken eggs with embryos, assessed on the same day. Larger
      voltages were recorded from E18 subjects than from E12 or E15 subjects. Because
      this could have been due to embryonic size (mass) and/or proximity to the
      electrodes, making age comparisons uninterpretable, we used standard deviation
      normalized and Z-score-based data transformations, comparing groups for relative
      deviations from basal voltages. E18 subjects still appeared more active than E12
      subjects, with E15 a transitional age, in contrast to results from earlier window
      based studies. The automated assessment method we used could enhance behavioral
      teratology studies of avian species.

PMID- 9919430
TI  - Behavioral development and olfactory learning in the honeybee (Apis mellifera).
AB  - Honeybees (Apis mellifera) can be readily conditioned in the laboratory to
      specific odors paired with a subsequent sucrose reward. A series of experiments
      are reported which demonstrate that the ability of bees to acquire and retain
      this learning is affected by the stage of behavioral development (caste). Results
      show rapid acquisition of the proboscis extension reflex (PER) conditioning in
      adult forager bees, however much slower acquisition and poorer retention of the
      same learning paradigm in younger adults, i.e., nurse bees and guard bees.
      Further, if nurse bees are made to forage precocially by manipulation of the hive
      population, these bees show excellent acquisition and retention of PER
      conditioning comparable to normal adult forager bees. Results are discussed in
      terms of olfactory learning requirements of bees performing caste-specific
      behaviors and the maturation of the bee nervous system.

PMID- 9919431
TI  - Consistency and change in the behavior of rhesus macaque abusive mothers with
      successive infants.
AB  - This study investigated the abusive behavior and parenting styles of 7 rhesus
      macaque mothers with infants born in 2 consecutive years. All subjects lived in
      captive social groups and were observed during the first 12 weeks of infant life.
      With the exception of 1 individual, mothers were generally consistent in the
      frequency with which they abused their successive infants. Similarities were also
      found in the temporal course of infant abuse, the use of the most common pattern
      of abuse, and some measures of parenting style, notably those reflecting maternal
      protectiveness. The findings of this study are discussed in relation to different
      hypothesized relationships between infant abuse and parenting style in macaques.

PMID- 9919432
TI  - The development of auditory event related potentials in the rhesus monkey (Macaca
      mulatta).
AB  - Auditory event related potentials were recorded from neonatal, 3-month, and 3
      year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably
      recorded at all ages. ABR latencies decreased with age. Age effects were greater
      the more centrally generated the wave. Wave I amplitude decreased with age, Wave
      II increased, and Wave IV remained about the same. Stimulus rate effects were
      greater in neonates than older monkeys. Stimulus frequency also affected the ABR,
      but not differentially as a function of age. Recording montage had a significant
      effect on the recorded waveform. Wave I tended to be larger in amplitude in
      horizontal recordings and front-back recordings, while the later waves were
      relatively more prominent in more vertical montages. Middle latency evoked
      responses and late potentials were less reliably recorded than the ABR. Their
      reproducibility improved with age. Auditory event related potentials are
      promising measures of auditory function for research requiring nonhuman primate
      models of the developing human.

PMID- 9919433
TI  - Extinction after regular and irregular reward schedules in the infant rat:
      influence of age and training duration.
AB  - Greater persistence in extinction is observed following inconsistent reward
      compared to that observed following consistent reward, an effect termed the
      partial reinforcement extinction effect (PREE). We report three experiments in
      which the extinction rates of random partially reinforced (PRF) or continuously
      reinforced (CRF) infant rat pups were compared to the extinction rate of pups
      trained with an alternative and regular schedule of partial reinforcement, known
      as patterned single alternation (PSA). In PSA, subjects learn to alternate speed
      of responding in anticipation of the regular alternation of reward and nonreward
      trials in the straight alley runway. In Experiment 1, 17-day-old PSA subjects
      showed CRF-like extinction rates; whereas in Experiment 2, in which extinction
      was initiated early in training prior to the onset of the PSA discrimination, PSA
      subjects showed prolonged, PRF-like extinction curves. In contrast, 12-day-old
      pups in Experiment 3 showed no reward-schedule-related differences in extinction,
      despite differences in behavior during acquisition. These results prompt a
      modification of Amsel's (1962) model of discrimination learning, and suggest the
      existence of a dissociation between different types of reward-related
      expectancies in the younger subjects.

PMID- 9919434
TI  - Epidemiologic and genetic approaches in the study of gene-environment
      interaction: an overview of available methods.

PMID- 9919435
TI  - Developing case definitions for symptom-based conditions: the problem of
      specificity.

PMID- 9919436
TI  - Development of the multiple metabolic syndrome: an epidemiologic perspective.

PMID- 9919437
TI  - Epidemiologic studies of beta agonists and asthma deaths.

PMID- 9919438
TI  - Epidemiology of the Revised European-American Lymphoma Classification subtypes.

PMID- 9919439
TI  - Epidemiologic studies of risk factors for cancer in pet dogs.

PMID- 9919440
TI  - Epidemiology and prevention of lung cancer in nonsmokers.

PMID- 9919441
TI  - Fertility drugs and ovarian cancer.

PMID- 9919442
TI  - Manifesto for emergency medicine in Europe. Council of the European Society for
      Emergency Medicine.

PMID- 9919443
TI  - Prospective use of platelet glycoprotein IIb/IIIa receptor blockers in the
      emergency department setting.
AB  - Platelets play a pivotal role in the pathophysiology of acute coronary syndromes
      (ACS) and thus are logical therapeutic targets for treatment of this disease
      process. Platelet glycoprotein (GP IIb/IIIa receptor antagonists, which interrupt
      the final common pathway of platelet aggregation, have been proven to reduce the
      30-day incidence of death, acute myocardial infarction (MI), and urgent
      revascularization in both high-risk and low-risk patients undergoing percutaneous
      intervention procedures. Three-year follow-up has indicated that these benefits
      appear durable. Recent large-scale randomized trials have demonstrated the value
      of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in
      unstable angina/non-Q-wave MI patients receiving pharmacologic management. And,
      emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as
      an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the
      list of indications for GP IIb/IIIa receptor antagonists expands to encompass the
      full spectrum of ACS, there is increasing interest in the potential use of these
      agents in the emergency department setting. The integration of GP IIb/IIIa
      receptor inhibitors into emergency department protocols will ultimately depend
      largely on whether these drugs prove to be safe and effective regardless of the
      direction of ST-segment deviation, and irrespective of whether definitive therapy
      will be invasive or conservative.

PMID- 9919445
TI  - A survey of sedation protocols used for emergency endotracheal intubation in
      poisoned patients in the French prehospital medical system.
AB  - The purpose of this study was to evaluate prehospital sedation protocols used by
      several French mobile intensive care units for difficult intubations in poisoned
      patients. This prospective, descriptive study was performed within the
      toxicological intensive care unit in a university hospital. Consecutive poisoned
      patients intubated during their airway management by prehospital medical teams
      were included. Intubating physicians completed a one-page checklist concerning
      the circumstances of endotracheal intubation. Intubation difficulty was
      significantly related to the nature of sedation protocols. The use of etomidate
      alone as an intubation sedative agent was associated with significantly poorer
      intubating conditions (47.2% difficult) than other sedative agents or
      neuromuscular blockade). Neuromuscular blockade with sedation in our series was
      associated with the lowest incidence of difficult intubations in poisoned
      patients. Sedation alone for intubation appears to be inadequate to achieve good
      intubating conditions in a significant proportion of patients.

PMID- 9919444
TI  - Prospective, double-blind, comparative fast-tracking trial in an academic
      emergency department during a period of limited resources.
AB  - The aim of this study was to determine the effectiveness of 'fast-tracking' in an
      academic emergency department (ED) during a period of limited resources and space
      constraints. This was a prospective, double-blind, comparative clinical trial.
      Fast-tracking was applied every other day between 08.00 and 17.30 hours. Patients
      meeting fast-tracking criteria, which were determined as allergy, dyspepsia,
      hypertension, urinary tract infection, urolithiasis, gastroenteritis, upper
      airway infection, minor lacerations, and soft tissue injuries with no sign or
      symptom of life-threatening illness or acute abdomen, were treated by a
      designated fast-tracking team. In the alternate days fast-tracking was not done,
      and the patients having the same criteria were recorded and followed as the
      control group. ED length of stays were determined for each patient, and at time
      of discharge a questionnaire was applied to determine patient satisfaction.
      Follow-up was performed by telephone survey at the 5th day of discharge. The
      median length of stay was 36 minutes for the fast-tracked group compared with 63
      minutes for the control group. The application of fast-tracking decreased ED
      length of stay and improved patient satisfaction in patients presenting with
      allergy, dyspepsia, upper airway infection, minor laceration, and soft tissue
      injury, but not in patients with gastroenteritis, urinary tract infection,
      hypertension, and urolithiasis. The rate of follow-up was 81% (n = 217), and
      there were no complications or hospitalizations to another hospital. It is
      concluded that fast-tracking is an applicable and useful system in an academic ED
      with limited resources, and decreases ED length of stay and improves patient
      satisfaction in a selected group of patients. Determination of fast tracking
      criteria must be individualized for each hospital according to resources.
      Additionally, fast-tracking seems to be safe when performed under strict criteria
      for patient selection.

PMID- 9919446
TI  - Straddle injuries--is current practice safe?
AB  - Genital injuries may be markers of sexual abuse and child protection issues
      should be considered when case present. This study evaluates the quality of
      history taking and the physical examination of children who present with straddle
      injuries to an accident and emergency department. A retrospective analysis of the
      accident and emergency case notes of children who presented over a 12-month
      period with straddle injuries was undertaken. A scoring system of risk factors
      was devised to help identify children at risk of sexual abuse and applied to the
      case notes. The results showed that the documentation of injuries was inadequate
      in the majority of cases, increasing the risk that cases of sexual abuse may be
      missed. Core questions which aid in the selection of children who require further
      evaluation have previously been identified. Utilizing the information from our
      findings we have devised a protocol for the assessment of children with straddle
      injuries which includes an action plan for the management of such cases.

PMID- 9919447
TI  - Predictors of success in the conversion of new-onset atrial fibrillation using
      oral propafenone.
AB  - We have investigated the relationship of clinical variables to successful
      cardioversion of atrial fibrillation (AF) to sinus rhythm using an oral loading
      dose of propafenone. Fifty consecutive patients with recent onset (< 72 hours)
      atrial fibrillation of various aetiologies were included in the study cohort. All
      patients were given the study medication while in the emergency department and
      then monitored for 8 hours. All patients converting to sinus rhythm (39 out of
      50, 78%) were discharged and re-evaluated at 24 hours and 30 days. We
      investigated the effect of clinical factors such as age, sex, presence of
      hypertension (HT), chronic obstructive lung disease (COPD), diabetes mellitus
      (DM), mitral stenosis (MS), congestive heart failure (CHF), coronary artery
      disease (CAD) and the duration of atrial fibrillation on conversion to sinus
      rhythm. Of these factors, univariate and multivariate analysis showed that only
      the duration of atrial fibrillation was a significant predictor of conversion (p
      = 0.002). Our results suggest that most patients with new-onset AF can be
      converted successfully to sinus rhythm with a low incidence of adverse reactions
      using oral propafenone in the emergency department.

PMID- 9919448
TI  - The socio-economic and demographic context of children's emergency injury visits
      in Helsinki in 1991-1994.
AB  - The aim is to study the association between age- and diagnosis-specific trauma
      visit rates and socio-economic and demographic variables in the city of Helsinki,
      Finland. A total of 19,772 home and leisure injury visits were analysed by random
      effects (REM) and Poisson regression models. Visit rates were calculated for age-
      and diagnosis-specific groups for each of the city's 33 health districts using
      the corresponding age-specific census data. In addition, the areas were ranked
      into three groups according to a socio-economic index measure. The annual visit
      rates of the three groups were calculated and the effect of distance on visit
      rates by socio-economic groups was analysed. In the case of pre-school children
      no correlation was found between explanatory variables and trauma visit rates. In
      the school-aged children group distance from the hospital (p < 0.001) correlated
      with childhood ambulatory visit rates. We found a rather modest difference in
      children's visit rates between unequal socio-economic areas. However, the demand
      for care was elastic for travelling distance (p < 0.05) in poorer suburbs but not
      in more affluent areas in the case of school-aged children. The probability of
      significant inequalities in children's trauma visit rates was small in Helsinki
      during 1991-94.

PMID- 9919449
TI  - Screening for domestic violence in the emergency department.
AB  - The objective of this study was to determine whether two brief screening
      questions at the time of emergency department triage can increase the detection
      of domestic violence. Two questions concerning domestic violence were asked by
      emergency department personnel (registered nurses, licensed practising nurses,
      physician assistants) to all adult patients presenting to an urban level one
      trauma centre from 1 January 1993 to 31 December 1993. Patients were excluded if
      they were in extremis, or active labour. All potential abused patients were
      referred to a social worker for verification and intervention. A total of 59,405
      patients were seen during the study period, and (79%) 46,929 participated. Of
      these, 132 (0.3%) total cases of domestic violence were identified. Of these 132
      cases, 123 (93%) of them were available for follow-up and social worker
      intervention. Of these 123 cases, 17 (14%) were identified by the initial
      screening questionnaire. Screening questions concerning domestic violence can
      identify a small number of otherwise occult cases. Simply asking about domestic
      violence by emergency department triage personnel is insufficient. Further study
      is needed to identify the presumed greater number of unrecognized cases.

PMID- 9919450
TI  - Thoracic trauma in the elderly.
AB  - Thoracic trauma in the elderly population constitutes a major challenge for both
      thoracic and trauma surgeons as their presentation and outcomes differ from the
      adult population in addition to their high morbidity and mortality. One hundred
      and one patients, 60 years of age or older, with thoracic trauma were treated at
      Dicle University School of Medicine during a 6-year period. Eighty-five per cent
      were male and 15% were female with a mean age of 64.5 years. The cause of
      thoracic injury was blunt in 77.2% and penetrating in 22.8% of the patients.
      Sixty-two patients (61.4%) had isolated thoracic injuries. The median Injury
      Severity Score (ISS) was 23. The morbidity rate was 23.8%. The mortality rate was
      16.8%. Seven of 10 patients (70%) who had an ISS greater than 25 died, whereas
      six of 24 (25%) patients with an ISS between 17 and 25, and four of 67 (5.9%)
      patients with an ISS less than 16 died. In the elderly the morbidity and
      mortality rates were higher for blunt trauma compared with penetrating trauma.
      For ISS greater than 25 the mortality rate was 71.4% for blunt and 66.6% for
      penetrating trauma. As the morbidity and mortality rate are significantly higher
      in the elderly patients the approach to these patients should include recognition
      of their high risk for morbidity and mortality, especially for those who had an
      ISS greater than 25.

PMID- 9919451
TI  - The clinical characteristics at the onset of a severe asthma attack and the
      effects of high frequency jet ventilation for severe asthmatic patients.
AB  - To clarify the relationship between the clinical characteristics and the effects
      of high frequency jet ventilation based on the differences in the speed of
      deterioration in severe asthmatic patients who required intubation and mechanical
      ventilation, we classified 37 severe asthmatics into two groups (acute onset
      group: n = 20, intubated within 24 hours; slow onset group: n = 17, intubated
      over 3 days) and measured the arterial blood gas values, the duration of
      mechanical ventilation, and the peak inspiratory pressure during synchronized
      intermittent mechanical ventilation with or without high frequency jet
      ventilation. The acute onset group showed a significantly higher incidence of
      cyanosis (75% vs. 41%, p < 0.05), an acute loss of consciousness (90% vs. 53%, p
      < 0.05), severe mixed acidosis with extreme hypercapnoea (pH 7.11 +/- 0.19, PaCO2
      94.1 +/- 10.7 mmHg, BE -8.3 +/- 1.7 mEq/l), and a more elevated peak inspiratory
      pressure (59.7 +/- 1.8 mmHg vs. 41.1 +/- 1.8 mmHg, p < 0.05) during synchronized
      intermittent mechanical ventilation at admission, compared with the slow onset
      group (p < 0.05). The slow onset group required a more prolonged mechanical
      ventilation than the acute onset group (5.4 +/- 4.0 vs. 3.0 +/- 2.4 days, p <
      0.05), in spite of a lower peak inspiratory pressure than that observed in the
      acute onset group, because of either a large amount of secretion or an infection
      in the airway. Both the high peak inspiratory pressure and the severe mixed
      acidosis with markedly elevated hypercapnoea were significantly reduced by the
      application of high frequency jet ventilation between the intra- and the inter
      groups. These findings thus indicated the existence of significant differences in
      the clinical features and pathogenesis of airway hyperreactivity between these
      two groups, and the application of high frequency jet ventilation to the status
      asthmaticus was thus found to be effective.

PMID- 9919452
TI  - Formation of emergency medicine in Italy.
AB  - In Italy departments of emergency medicine and emergency medical service systems
      (EMS) were first set up at the end of the 1970s. Since that time many dramatic
      and significant changes have taken place in the care of the critically ill
      patient. In Italy the interest in emergency problems and the need for emergency
      intervention have increased considerably. Nevertheless several problems still
      have to be solved in order to obtain a standardized organization of the emergency
      system in Italy and uniform training of emergency care providers.

PMID- 9919453
TI  - Severe encephalopathy in a child: an uncommon cause.
AB  - Cat scratch disease (CSD) is usually a self-limited disease. Although extremely
      uncommon, the involvement of the central nervous system has been previously
      reported in CSD. The intention of this paper is to make physicians aware that CSD
      could be complicated by encephalopathy. Seizures in some patients could be the
      only clinical manifestation and are resistant to the common anti-epileptic
      therapy. The seizures resolve with supportive care.

PMID- 9919454
TI  - Metal fume fever.
AB  - Metal fume fever (MFF) is an acute self-limited, flu-like illness resulting from
      inhalation of metal oxides. Despite the well-documented history of MFF in the
      medical literature, the illness may remain unrecognized because it may mimic a
      viral illness. The case of a patient with MFF due to galvanized steel welding
      presenting to the emergency room is described.

PMID- 9919455
TI  - Omeprazole and the development of acute hepatitis.
AB  - Omeprazole has been used with increasing frequency for the treatment of
      conditions such as reflux oesophagitis, peptic ulcer disease, and Zollinger
      Ellison syndrome. Several sequelae have been documented in the literature, but
      there has been limited indication of significant hepatotoxicity. We present a
      unique case of acute hepatitis secondary to the use of omeprazole that was
      resolved spontaneously with discontinuation of the drug.

PMID- 9919456
TI  - Prehospital thrombolysis in acute myocardial infarction.
AB  - Efficacy of reperfusion therapy in acute myocardial infarction is strictly time
      dependent. As is evidenced by several studies, most benefit in terms of
      myocardial salvage and short- and long-term mortality is achieved with initiation
      of therapy within the first 60-90 minutes after onset of symptoms. Nearly
      exclusively, prehospital initiation of thrombolysis makes it possible to take
      advantage of this early time window. Moreover a time gain of more than 30
      minutes, up to 130 minutes, is possible by prehospital initiation of
      thrombolysis, depending on local circumstances. Randomized studies yielded a
      better outcome when a time gain of > or = 90 minutes was achieved. Since it has
      been shown that prehospital diagnosis of an acute myocardial infarction is
      reliable and out-of-hospital initiation of therapy has no additional specific
      risk, patients seen within the first 60-90 minutes after onset of symptoms or for
      whom a relevant time gain of > or = 90 minutes can be expected are ideal
      candidates for, and therefore should receive, prehospital thrombolysis.

PMID- 9919457
TI  - Just a hip fracture?

PMID- 9919458
TI  - Qualitative research methods in health technology assessment: a review of the
      literature.

PMID- 9919459
TI  - Cardiothoracic and vascular anesthesia.

PMID- 9919460
TI  - Critical issues in early extubation and hospital discharge in thoracic oncology
      surgery.
AB  - Of the 3,231 thoracic procedures performed between July 1, 1994, and June 30,
      1996, 8.9% of patients were ventilated postoperatively; 3.1% required an
      intensive care unit (ICU) stay of a median of 8 days. Of those patients admitted
      to the ICU, 29% died; 10% of patients requiring postoperative ventilation were
      subsequently admitted to the ICU. The majority of thoracic surgical patients are
      extubated at the end of the procedure. Those patients that are left intubated and
      go to the ICU have a higher mortality rate and a prolonged hospital stay.

PMID- 9919461
TI  - Ensuring early discharge following major surgery: orthopedic surgery.
AB  - Managed care, critical pathways, and length of stay issues have a major impact on
      current hospital policy and patient care. In orthopedic surgery, significant
      strides have been made in improving efficiency, decreasing costs, and reducing
      length of stay. Use of vertical pathways, especially the first day of admission,
      the day of surgery, is important for efficient patient care. As anesthesiologists
      involved in the process, we must be certain that patient care is not compromised
      in an attempt to save money or achieve early discharge. In many studies, pain
      management, type of anesthesia, and amount of blood loss are not significant
      factors in length of hospital stay. These factors must be approached as quality
      of-life issues and appropriate decisions made.

PMID- 9919462
TI  - Patient selection and anesthetic management for early extubation and hospital
      discharge: CABG.
AB  - Three model systems have been described that may facilitate an increase in the
      numbers of patients passing through the hospital within the resource allocation
      available: (1) early fast-track extubation, < 3 hours after surgery, (2) planned
      intensive care unit discharge < 18 hours, and (3) early hospital discharge < 5
      days. Thus far, studies have not clearly identified patient group or risk
      demonstrating a need for prolonged intubation or delayed intensive care unit and
      hospital length of stay. It thus appears appropriate to suggest that all patients
      be considered suitable for early extubation, mobilization, and hospital
      discharge. An increase in the proportion of patients eligible for a more rapid,
      but safe, progression through their operative procedures may be facilitated by
      pharmacologic intervention or alteration in anesthetic technique. Prevention of
      adverse perioperative myocardial outcome by inhibition of stress responses and
      careful control of intraoperative cardiovascular variables is most easily
      achieved by high thoracic (C7-T1) epidural conduction block or by a high-dose
      opioid anesthetic technique using remifentanil. The ultrashort action of
      remifentanil facilitates the ability to plan and control the period of recovery
      of spontaneous ventilation and extubation while providing profound reduction of
      intraoperative stress responses and hemodynamic stability. Safe extubation
      requires that the patient be alert and cooperative, be hemodynamically stable and
      warm, is not bleeding, and has adequate respiratory function. Interventions with
      anti-inflammatory and hemostatic agents such as the serine protease inhibitor
      aprotinin or with corticosteroids can have a major impact on achieving the
      criteria needed to ensure rapid discharge from the intensive care unit.

PMID- 9919463
TI  - Ischemic injury and its prevention.
AB  - Perioperative ischemia is common in patients at risk of or with known artery
      disease undergoing noncardiac or cardiac surgery. Resultant ischemic injury can
      lead to a delay in extubation and hospital discharge, impaired quality of life
      after surgery, and a disproportionate consumption of health resources. Our goal
      as anesthesiologists is to prevent this poor perioperative cardiac outcome, to
      continually strive for improved patient care, and to reduce medical resource
      consumption. These goals are the driving force behind the recent increased
      interest in the use of minimally invasive direct vision coronary artery bypass
      graft techniques. This report discusses the definition and etiology of ischemia
      and the perioperative management strategies available to prevent ischemic injury,
      with emphasis on cardioprotective strategies (ischemic reconditioning, regional
      anesthesia, substrate provision) for minimally invasive direct vision coronary
      artery bypass surgery. Brief mention is also made of ischemic injury to other
      organ systems that may delay patient recovery.

PMID- 9919464
TI  - Factors that influence early extubation: bleeding.
AB  - Excessive bleeding after cardiac surgery is an important factor that can prevent
      early extubation. Hemostatic derangement is well recognized to be associated with
      cardiopulmonary bypass, with many possible contributing factors resulting in
      coagulation defects and fibrinolytic pathway activation. Measures to optimize
      hemostasis are critical when managing patients for whom early extubation and
      hospital discharge are goals. The intraoperative evaluation of the hemostatic
      system with tests like the thrombelastogram and the use of therapeutic agents
      such as aprotinin are simple, safe, and effective methods of achieving these
      goals.

PMID- 9919465
TI  - The implications of hypothermia for early tracheal extubation following cardiac
      surgery.
AB  - Thermoregulation is impaired during anesthesia for cardiac surgery.
      Redistribution of body heat and heat loss to the environment result in mild
      hypothermia before cardiopulmonary bypass. Maintenance of normothermia, rather
      than hypothermia, may facilitate early tracheal extubation. Hypothermia alters
      the distribution and decreases the metabolism of most drugs, including anesthetic
      drugs and muscle relaxants, thus prolonging recovery. Postoperative shivering
      increases metabolic rate and potentially leads to myocardial ischemia; prevention
      is therefore critical to the success of early tracheal extubation after cardiac
      surgery. Coagulopathies, increased incidence of surgical wound infection, and
      perioperative cardiac morbidity are other potential risk factors identified in
      noncardiac patients. Hypothermia, however, does have potential benefits to the
      patient, including protection from cerebral ischemia and hypoxemia. Mild core
      hypothermia (approximately 34 degrees C) may represent the optimal balance
      between risks and benefits for fast-track patients.

PMID- 9919466
TI  - Impact of early tracheal extubation on hospital discharge.
AB  - Economic realities of the continuing increased utilization of cardiac surgery in
      the 1990s have led to the practice of early tracheal extubation and shortening of
      the length of intensive care unit and hospital stays. In this era of cost
      containment and physician report cards, we are held accountable for patients'
      outcome in terms of mortality, morbidity, quality of life, length of stay, and
      cost of care. This report outlines the factors that influence costs of cardiac
      surgery. These include patient risk, anesthesia, surgical, intensive care unit,
      and health care systems or hospital factors. The current literature on outcome,
      utilization, and cost implications of early tracheal extubation in cardiac
      surgery is summarized and discussed. It has been demonstrated that early
      extubation anesthesia is safe and cost-effective and can improve resource
      utilization in cardiac surgery, but to achieve a maximum cost benefit from fast
      track or early extubation anesthesia in cardiac patients, team organization of a
      fast-track cardiac surgery program must be implemented. A perioperative clinical
      pathway management in fast-track cardiac surgery is presented.

PMID- 9919467
TI  - Homocysteine and cardiovascular disease. Overview.

PMID- 9919468
TI  - Novel risk factors for vascular disease: the homocysteine hypothesis of
      cardiovascular disease.
AB  - The possibility that modest elevations in the level of blood homocysteine
      (hyperhomocysteinaemia) could contribute to cardiovascular disease arose from
      investigation of patients with rare, severe homocysteine elevations caused by
      cystathionine beta-synthase deficiency. Such patients often had thromboembolic
      events before the age of 30 years. Since the established cardiovascular risk
      factors could only partly account for the occurrence and severity of vascular
      disease in the general population, other risk factors had to exist, and
      homocysteine elevation seemed to be a possible candidate. Australian case-control
      studies identified an association between mild homocysteine elevation and early
      onset coronary disease, and also with chronic renal failure. Patients in the
      latter group have a high prevalence of unexplained vascular disease and
      particularly high homocysteine levels. Such elevations in levels of homocysteine
      in vascular patients could usually be normalised by daily supplementation with
      folic acid (1-5 mg) while in patients with chronic renal failure 5 mg of folic
      acid daily markedly reduced the increased concentrations of homocysteine. These
      initial observations have been confirmed by many investigators and biologically
      plausible mechanisms for homocysteine-induced vascular dysfunction, and
      particularly endothelial dysfunction, have been identified. However, associations
      between hyperhomocysteinaemia and other risk factors, such as smoking and
      hypertension, have also been documented and need to be controlled for when
      assessing any increase in risk that homocysteine may independently confer.
      Although it has been established that lowering the greatly elevated blood
      homocysteine levels in homocystinuria, due to cystathione beta-synthase
      deficiency, unquestionably reduces cardiovascular risk, it remains to be
      determined whether normalising mild homocysteine elevation could reduce
      cardiovascular risk. Trials to test this possibility have been initiated and
      others are planned.

PMID- 9919469
TI  - Folic acid, homocysteine and one-carbon metabolism: a review of the essential
      biochemistry.

PMID- 9919470
TI  - Plasma homocysteine and coronary heart disease: systematic review of published
      epidemiological studies.

PMID- 9919471
TI  - Homocysteine and vascular disease: nature or nurture?
AB  - There is now abundant evidence that elevated plasma total homocysteine is a risk
      factor for vascular disease in general and for cardiovascular disease in
      particular. Plasma concentrations of homocysteine are modulated by both genetic
      and environmental factors, among which inherited enzymatic defects and
      nutritional deficiencies respectively, are probably the most important. Other
      environmental factors such as smoking, also influence plasma homocysteine
      concentrations. The role of nutritional and other environmental factors had been
      underestimated until recently, when a final examination of the contribution of
      inherited defects became possible with the advent of DNA isolation and sequencing
      of large population samples. There is now consistent evidence from many studies
      that plasma homocysteine levels are inversely correlated with plasma folate,
      pyridoxal 5'-phosphate and cobalamin levels. This finding, together with that of
      significant lowering of homocysteine levels achieved with folate supplementation,
      constitutes a basis for optimism in reducing cardiovascular risk. As yet, no
      randomised control trial has been carried out to test this hypothesis.

PMID- 9919472
TI  - Pathogenesis of vascular disease in hyperhomocysteinaemia.
AB  - Elevated plasma homocysteine is an independent risk factor for atherosclerosis
      and thrombosis. The exact mechanism by which homocysteine exerts its
      atherothrombotic action is still unclear. Accumulating evidence suggests that
      hyperhomocysteinaemia leads to endothelial injury and dysfunction, mediated by
      free radicals generated during the oxidation of homocysteine. Homocysteine also
      stimulates the proliferation of vascular smooth-muscle cells and inhibits the
      growth of vascular endothelial cells. Elevated homocysteine levels may also
      promote thrombosis by increased generation of thrombin. Other possible mechanisms
      for homocysteine-mediated atherogenesis include: the altered methylation of DNA
      and altered regulatory proteins associated with cell membrane, decreased
      bioavailability of nitric oxide, increased elastolysis and collagen accumulation,
      overstimulation of N-methyl-D-aspartate receptors and excessive adhesion of
      monocytes and neutrophils to endothelium. Understanding the mechanisms in vivo by
      which hyperhomocysteinaemia is associated with vascular disease may provide new
      approaches to prevention and treatment of atherothrombosis.

PMID- 9919473
TI  - Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk?
      Design of clinical trials to test the homocysteine hypothesis of vascular
      disease.

PMID- 9919474
TI  - Homocysteine levels and coronary heart disease in Syria.
AB  - BACKGROUND: Coronary artery disease and disturbances of lipid levels are common
      in Arab countries. OBJECTIVE: To assess homocysteine as a cardiovascular risk
      factor. METHOD: We compared 133 men with angiographically documented coronary
      heart disease with 130 age-matched asymptomatic men. RESULTS: Cases had more
      hypertension and diabetes and higher levels of total cholesterol, low-density
      lipoprotein cholesterol, triglycerides, fibrinogen, and homocysteine than did
      controls. The homocysteine level distribution of cases was shifted toward higher
      concentrations (P < 0.05) compared with those in controls. When patients with one
      vessel, two-vessel, and three-vessel disease were compared, only levels of
      fibrinogen and homocysteine were associated with the numbers of vessels involved.
      Homocysteine level was not correlated to fibrinogen and lipid concentrations. A
      multiple regression analysis revealed that only age (P = 0.06) and smoking (P =
      0.04) were marginally related to homocysteine concentrations. Homocysteine
      concentrations in cases were significantly different than those in controls, even
      after adjustment for all covariates (P < 0.006). CONCLUSION: Hyperhomocysteinemia
      is independently associated with coronary artery disease in Arab men.
      Furthermore, fibrinogen concentrations are also an important risk factor for Arab
      men.

PMID- 9919475
TI  - Longitudinal analysis of the effect of smoking cessation on cardiovascular risk
      factors in a community sample: the Busselton Study.
AB  - BACKGROUND: Cessation of smoking is known to have health benefits, but
      individuals who give up smoking can also suffer adverse effects. This study
      investigated the effects of smoking cessation on cardiovascular risk factors in a
      community-based sample. METHODS: Longitudinal risk factor data were analysed in
      1372 women and 888 men who took part in population-based mass health screenings
      in the rural town of Busselton, Western Australia. Age-adjusted changes in body
      weight, forced expiratory volume in 1 s (FEV1), forced vital capacity, blood
      pressure and total cholesterol over 3-year and 6-year follow-up periods were
      compared for 235 ex-smokers ('quitters'), 1499 never-smokers and 526 continuing
      smokers. RESULTS: In women, weight gain was larger in 'quitters' than in
      continuing smokers after 3 years (1.74 versus 0.32 kg, P = 0.015) and after 6
      years (2.39 versus 1.24 kg, P = 0.085). Male 'quitters' had gained significantly
      more weight after both 3 years (2.84 versus 0.93 kg, P < 0.001) and 6 years (4.46
      versus 2.40 kg, P < 0.001). Although FEV1 declined less in 'quitters' than in
      continuing smokers, this was statistically significant only for men and women
      aged less than 45 years. Smoking cessation was associated with smaller increases
      in cholesterol level in women, but not in men. Smoking cessation had no
      significant effect on changes in forced vital capacity or blood pressure.
      CONCLUSIONS: Smoking cessation has different consequences for cardiovascular risk
      factors in men and women. Although giving up smoking is associated with weight
      gain in both men and women, the magnitude of the gain is larger in men. Smoking
      cessation has beneficial effects on lung function, especially in younger people,
      and on lipid levels in women, but this requires further study. Smoking cessation
      does not appear to influence blood pressure.

PMID- 9919476
TI  - Lipoprotein (a), lipids, aspirin, and risk of myocardial infarction in the
      Physician's Health Study.
AB  - BACKGROUND: Previously reported data from the Physicians' Health Study indicate
      that there is no association between lipoprotein (a) level and subsequent risk of
      myocardial infarction among members of a large cohort of middle-aged men followed
      up prospectively for an average of 60.2 months. OBJECTIVE: To investigate whether
      this null finding is related to the generally favorable lipid profile of the
      cohort or to randomized assignment of aspirin. METHODS: In a follow-up analysis
      of 296 confirmed cases of myocardial infarction and 296 controls, we evaluated
      the association between lipoprotein (a) level and cardiovascular risk for those
      with and without hyperlipidemia as well as for those randomly allocated aspirin
      treatment and placebo. RESULTS: For those with total cholesterol levels > or =
      200 mg/dl, the age-adjusted smoking-adjusted relative risks of a first myocardial
      infarction associated with lipoprotein (a) levels above the 25th, 50th, 75th,
      90th, and 95th percentiles of the control distribution were 0.9, 1.1, 1.6, 1.7
      and 1.0 (all NS; P for trend 0.5). Among those with total cholesterol levels <
      200 mg/dl, the adjusted relative risks of myocardial infarction associated with
      these cutoff points were 0.9, 0.7, 1.2, 0.7, and 1.4 (all NS; P for trend 0.7).
      Analyses limited to those with total cholesterol levels > or = 240 mg/dl or to
      men with higher than normal total cholesterol: high-density lipoprotein ratios
      revealed similar null findings. We observed no significant interaction between
      total cholesterol and lipoprotein (a) levels for these groups. For those randomly
      allocated aspirin, the age-adjusted and smoking-adjusted relative risks of
      myocardial infarction associated with lipoprotein (a) levels above the 25th,
      50th, 75th, 90th, and 95th percentile cutoff points were 0.9, 0.9, 1.5, 1.5, and
      1.0 (all NS; P trend 0.9). For those randomly allocated placebo, the age-adjusted
      and smoking-adjusted relative risks of myocardial infarction associated with
      lipoprotein (a) levels were 0.8, 0.9, 1.4, 1.5, and 1.3 (all NS; P trend 0.9).
      There was no significant interaction between aspirin and lipoprotein (a) level
      for any of these groups. Similar null findings were observed in analyses
      evaluating evidence for there being a trend across increasing quartiles of
      lipoprotein (a). CONCLUSION: These prospective data indicate that neither levels
      of lipids nor aspirin treatment modified the lack of overall effect of
      lipoprotein (a) on the risk of a first myocardial infarction in the Physicians'
      Health Study.

PMID- 9919477
TI  - Bibliography current world literature.

PMID- 9919478
TI  - Contents of erythorbic acid in the tissues of guinea pigs intraperitoneally
      administered erythorbic acid.
AB  - The contents of ascorbic acid (AsA) and erythrobic acid (ErA) in the tissues of
      guinea pigs intraperitoneally injected with AsA and/or ErA were determined to
      learn the difference in their retention in the tissues. After 10 d of AsA
      depletion, the guinea pigs were intraperitoneally injected with 5 mg of AsA, or 5
      mg of ErA, or 5 mg of each. At day 5 of repletion, the guinea pigs were killed
      and liver, adrenal glands, spleen, and kidneys were removed. AsA and ErA in these
      tissues were measured by using HPLC. The contents of AsA in the tissues of only
      the AsA-injected guinea pigs were similar to those of the AsA- + ErA-injected
      guinea pigs. The contents of ErA in the tissues of the ErA-injected guinea pigs
      were higher than those of the AsA- + ErA-injected guinea pigs, but apparently
      lower than the contents of AsA in the AsA-injected guinea pigs. ErA was scarcely
      retained in the tissues of guinea pigs.

PMID- 9919479
TI  - Suspension "hypokinesia/hypodynamia" may decrease bone mass by stimulating
      osteoclast production in ovariectomized mice.
AB  - This study was conducted to examine, in detail, the histological changes in the
      femurs of suspended ovariectomized (OVX) mice to assess the role of mechanical
      stress on bone remodeling. Suspended-OVX, suspended-sham-ope, nonsuspended-OVX,
      and nonsuspended-sham-operated mice underwent operations 8 weeks after birth.
      Immediately after operation, hypokinesia/hypodynamia was created by a suspension
      harness for one week. Five specimens in each group were sacrificed 9 weeks after
      birth. The trabecular bone of the femurs in the suspended-OVX mice was removed
      and replaced extensively by bone marrow. The number of tartrate-resistant acid
      phosphatase (TRAP)-positive cells was larger in the suspended-OVX mice than in
      the remaining three groups. No significant differences in the number of TRAP
      positive cells were found between the suspended-sham-ope, nonsuspended-OVX and
      nonsuspended-sham-ope mice. The femurs of the OVX mouse with suspension
      "hypokinesia/hypodynamia" thus exhibits extensive trabecular bone loss in
      association with an increase of osteoclasts.

PMID- 9919481
TI  - Reversibility of the curdlan feeding effects on the morphological structure of
      intestinal mucosa in rats.
AB  - We reported in the previous paper that rats fed a curdlan diet showed significant
      increases in the weight of the cecum and its contents, a decrease in fecal wet
      weight, a retardation in the transit time of the gastrointestinal tract and
      morphological changes of the ileal and cecal mucosal surface when compared with
      the rats fed a cellulose diet. In the present study, we intended to learn if the
      curdlan effects on the morphological structure of intestinal mucosa were
      reversible. When rats were fed on the curdlan diet for 2 weeks followed by a
      cellulose diet for another 2 weeks, the cecum and cecal contents were not
      different from those of the cellulose group. The transit time of the
      gastrointestinal tract of the curdlan-followed-by-cellulose group was shorter
      than that of the curdlan group, whereas it was longer than that of the cellulose
      group. In scanning electron micrographs, the ileal villi of the curdlan-followed
      by-cellulose group were normal, as in the cellulose group. However, their ileal
      and cecal microvilli were similar to those of the curdlan group, that is, the
      microvilli were crowded and more tightly packed, and some appeared to have been
      squeezed out. From these results, it was concluded that the effects of the
      curdlan feeding were only partially reversible, but the effects on the surface
      structure of intestinal mucosa were still sustained even after curdlan feeding of
      2 weeks was discontinued. This might result from response to the high viscosity
      of the intestinal contents remaining after discontinuation of the curdlan.

PMID- 9919480
TI  - Effects of soluble dietary fibers on lipid metabolism and activities of
      intestinal disaccharidases in rats.
AB  - The present study was aimed to investigate the effects of indigestible dextrin
      and polydextrose, soluble dietary fibers with low molecular weight, on lipid
      metabolism and disaccharidase activities of intestinal mucosa in rats fed a high
      sucrose diet. Their effects were compared with those of well-known soluble
      fibers, pectin, and guar gum, and also with an insoluble fiber, cellulose.
      Dietary fibers added to diets at the 5% (w/w) level were alpha-cellulose, pectin,
      guar gum, indigestible dextrin, and polydextrose. Male Sprague-Dawley rats were
      given free access to test diets for 6 weeks. Body weight gain was the lowest in
      rats fed guar gum, the highest in rats fed cellulose, and in-between in rats fed
      other diets. Although guar gum, pectin, and indigestible feeding dextrin had
      lower plasma lipid values than cellulose feeding did, the differences were
      statistically insignificant. Liver triglyceride of the guar gum-fed group was
      about a third that of the cellulose-fed group, but although those of rats fed
      polydextrose, indigestible dextrin, and pectin were lower than that of cellulose,
      the differences were insignificant. Liver cholesterol and phospholipid
      concentrations were similar among groups. Daily fecal excretion of total lipid,
      cholesterol, and bile acids were highest in rats fed guar gum, followed by pectin
      fed and cellulose-fed rats, and the lowest in rats fed indigestible dextrin and
      polydextrose. Jejunal sucrase activity was low in the order of guar-gum,
      polydextrose, indigestible dextrin, pectin, and cellulose. The results indicate
      that the hypolipidemic effect of soluble dietary fibers would be lessened with
      reduction in molecular weight, but that the lower sucrase activity by soluble
      fibers with low molecular weight might be beneficial for hypoglycemic effect.

PMID- 9919482
TI  - Effect of orally administered reduced- and oxidized-glutathione against
      acetaminophen-induced liver injury in rats.
AB  - To investigate the effects of orally administered reduced-glutathione (GSH) and
      oxidized-glutathione (GSSG) on liver GSH repletion and liver injury,
      acetaminophen (AAP) highly loaded rats were used. Orally administered GSH,
      dependent on dosage, indicated a protective effect against AAP-induced
      hepatotoxicity. This effect was associated with a recovery of liver GSH levels.
      Orally administered GSSG also indicated liver GSH recovery and hepatotoxicity
      inhibition to the same extent as orally administered GSH. Because
      intraperitoneally administered GSH did not indicate liver GSH recovery, the
      replenishment of GSH levels after orally administered GSH is thought to be
      produced through the degradation of GSH into its constituent amino acids in the
      intestine and their re-synthesis in the liver. On the other hand, orally
      administered GSH indicated a lower liver GSH recovery than orally administered
      cysteine prodrugs did, although the hepatotoxicity inhibitory degree was similar.
      Thus orally administered GSH may have another hepatoprotective system besides the
      resynthesis of its constituent amino acids. The current study establishes that
      orally administered glutathione, both GSH and GSSG, is a useful tool to recover
      liver GSH levels and to prevent liver injury.

PMID- 9919483
TI  - Effect of sex hormones on rat liver cytosolic alcohol dehydrogenase activity.
AB  - Rat liver cytosolic alcohol dehydrogenase (ADH) activity is known to be
      significantly higher in females than in males. To elucidate a possible mechanism
      of sex difference in the ADH activities, we studied the in vivo effects of the
      administrations of beta-estradiol, progesterone or testosterone, and castrations
      (orchiectomy and ovariectomy) on the ADH activities in male and female Sprague
      Dawley adult rats. Furthermore, we studied the ADH activities in six liver
      portions of sham-operated male, orchiectomized male, and female rats. The ADH
      activities were higher in orchiectomized male rats than in sham-operated male
      rats. These results were observed in all liver portions. The administration of
      testosterone (5 mg/kg BW, twice a day for 7 d) to orchiectomized male rats
      significantly decreased ADH activities. The ADH activities in ovariectomized
      female rats were comparable with those in sham-operated female rats. The
      administration of beta-estradiol (50 micrograms/kg BW, once every 2 d for 20 d)
      or progesterone (75 micrograms/kg BW, once every 2 d for 20 d) to rats increased
      the ADH activities in males more than in females. These results suggest that the
      inhibitory action of androgen and the slight facilitatory actions of progestin
      and estrogen are involved in the mechanism of sex difference in adult rat liver
      cytosolic ADH activity.

PMID- 9919484
TI  - Degradation of serum albumin by rat liver and kidney lysosomes.
AB  - Lysosomes were isolated from the livers and from the kidneys of rats treated or
      not treated with the cysteine proteinase inhibitor leupeptin, and the levels of
      the intralysosomal serum albumin of the leupeptin-treated rats were compared with
      those of the saline-treated control rats. Leupeptin caused an intralysosomal
      accumulation of albumin in vivo because of its potent inhibition of lysosomal
      protein degradation. In fact, the lysosomes isolated from the livers and kidneys
      of leupeptin-treated rats almost completely lost their ability to degrade rat
      albumin in vitro. These findings show that the lysosomes are subcellular sites of
      the degradation of unlabeled serum albumin in these tissues. They also suggest
      that cysteine proteinases sensitive to leupeptin are involved in the lysosomal
      degradation of albumin. Albumin was degraded by total lysosomal enzymes in vitro.
      It was also degraded by the lysosomal extract being devoid of cathepsins H and J,
      prepared from rat kidney. The degradation of albumin by total lysosomal enzymes
      in vitro was greatly suppressed by a cysteine proteinase inhibitor, cystatin
      alpha, with no inhibition of cathepsins B and L. It was slightly suppressed by N
      (L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-prol ine (CA-074), a
      selective inhibitor of cathepsin B, and by pepstatin, an inhibitor of cathepsin
      D, whereas it was markedly suppressed by a combination of cystatin alpha and
      either CA-074 or pepstatin. These and associated findings show that cystatin
      alpha-sensitive cysteine proteinase(s), which is distinct from cathepsins B, H,
      L, and J, and cathepsins B and D are involved in the lysosomal degradation of
      albumin.

PMID- 9919486
TI  - Thiamin-binding protein from sunflower seeds.
AB  - A thiamin-binding protein was isolated from sunflower seeds. Its molecular mass
      was estimated to be 230 kDa by gel filtration. The protein was suggested to be
      composed of six subunits, which consisted of polypeptides linked by disulfide
      bond(s). The protein contained a large amount of glutamine or glutamic acid (19.9
      mol%) and asparagine or aspartic acid (11.1 mol%). The levels of tryptophan and
      valine in the protein were low. These properties of the thiamin-binding protein
      were similar to those of helianthinin. Optimum pH for the thiamin-binding
      activity of the protein was 8.0 to 9.0. The thiamin-binding activity was not
      inhibited by thiamin monophosphate, thiamin pyrophosphate, oxythiamin, or
      pyrithiamin. These properties of the thiamin-binding protein from sunflower seeds
      were similar to those from buckwheat seeds, but not to those from rice seeds and
      sesame seeds.

PMID- 9919485
TI  - Quantitative analysis of Gly m Bd 28K in soybean products by a sandwich enzyme
      linked immunosorbent assay.
AB  - A sandwich enzyme-linked immunosorbent assay for the soybean allergen, which
      consists of a monoclonal antibody (D4) as the fixing (first) antibody and another
      peroxidase-conjugated monoclonal antibody (C5) as the second, has been developed.
      Both D4 and C5 monoclonal antibodies strongly bound to the guanidine/HCl
      denatured allergen, Gly m Bd 28K. Therefore the samples used in the present
      experiment were extracted with sodium phosphate buffer (pH 8.0) containing 6 M
      guanidine and 10 mM 2-mercaptoethanol, then completely dialyzed against phosphate
      buffered saline (PBS). The dialyzed samples were subjected to the assay. Various
      soybean products were observed to contain the allergen at high concentrations,
      such as soybean protein isolate (SPI), tofu, kori-dofu, and yuba, but its content
      in soy milk and abura-age were found to be low. In fermented products such as
      natto, soy sauce, and miso, and even in the processed foods with soybean protein
      isolate (SPI), the allergen was not detected. These results were also confirmed
      by an immunoblotting technique with D4.

PMID- 9919487
TI  - Effects of green tea catechin on hepatic microsomal phospholipase A2 activities
      and changes of hepatic phospholipid species in streptozotocin-induced diabetic
      rats.
AB  - In this study, male Sprague-Dawley rats weighing 70 +/- 5 g were divided into a
      control (normal) group and three different diabetes mellitus (DM) groups that
      were supplemented with catechin-free (DM-0C), 0.5% catechin dietary (DM-0.5C),
      and 1% catechin (DM-1.0C). The animals were maintained on an experimental diet
      for four weeks. At this point, they were injected with streptozotocin (STZ) to
      induce diabetes, and they were sacrificed on the 6th day to determine the
      activities of phospholipase A2 (PLA2) and the changes of phospholipid species by
      catechin supplementation. In liver tissues, no significant differences were found
      between the PC hydrolysis of a normal group and a diabetic group; however, PE
      hydrolysis of the DM-0C, DM-0.5C, and DM-1.0C groups increased by 68.9%, 34.01%,
      and 26.9%, respectively, compared with the normal group. Although the PLA2
      activity of the DM-0C group in the liver tissues increased 91% compared with the
      normal group, the PLA2 activity of DM-0.5C and DM-1.0C, which were fed catechin,
      increased 50% and 56%, respectively, compared with the normal group. In the liver
      tissues, peroxide values of the DM-0C, the DM-0.5C, and the DM-1.0C groups were
      increased 109%, 32.8%, and 46.7%, respectively, compared with the normal group.
      Based on these results for STZ-induced diabetic rats, lipid peroxidation seems to
      be accelerated specifically with the increased PLA2 activities. Thus if
      antioxidants like catechin were supplementation, the activity of PLA2 and PE
      hydrolysis can be altered and the accumulation of lipid peroxide would be
      decreased. Therefore we concluded that the antioxidant catechin for diabetic
      animals can significantly reduce PLA2 activities and lipid peroxide formation.

PMID- 9919488
TI  - Relative importance of phytohemagglutinin (lectin) and trypsin-chymotrypsin
      inhibitor on bean (Phaseolus vulgaris L) protein absorption and utilization by
      the rat.
AB  - The main objective of this work was to perform a comparative study of the
      antinutritional and/or toxic properties of phytohemagglutinin and trypsin
      chymotrypsin inhibitor extracted from the seed of a commercial cultivar of edible
      bean used in Brazil. Bean proteins were extracted in acidic salt solution and
      fractionated by dialysis and centrifugation, then freeze-dried. The total freeze
      dried bean extract and the globulin or albumin protein fraction were resuspended
      in distilled water and heated (100 degrees C, 30 min) for inactivation of
      hemagglutinin. Diets were prepared with unheated bean protein fractions and
      heated ones (100% trypsin inhibitor activity, but 0% phytohemagglutinin
      activity). As a result, the inhibition of growth and poor dietary protein
      utilization were observed in rats fed diets containing unheated bean protein
      fractions, but not in rats fed diets containing heated fractions. It was thus
      assumed that phytohemagglutinin is the main antinutritional and toxic factor that
      in dry bean (Phaseolus) protein and that trypsin inhibitor (Bowman-Birk type) did
      not interfere with rat growth.

PMID- 9919489
TI  - alpha-tocopherol protects the peroxidative modification of LDL to be recognized
      by LDL receptors.
AB  - BACKGROUND: Peroxidatively modified low-density lipoprotein (LDL) may contribute
      to the atherosclerotic process; therefore, protecting LDL against peroxidation
      may reduce or retard the progression of atherosclerosis. We evaluated the effect
      of alpha-tocopherol on copper-catalyzed LDL peroxidative modification. METHODS:
      The protective effects of alpha-tocopherol on copper-catalyzed LDL peroxidative
      modification were examined by measurement of the concentration of lipid
      hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via
      the LDL receptor-mediated pathway. RESULTS: The measurement of concentration of
      lipid hydroperoxides in LDL showed that alpha-tocopherol inhibited the
      peroxidative modification of LDL. Also, alpha-tocopherol preserved the ability of
      LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same
      extent as native LDL. CONCLUSION: These findings indicate that alpha-tocopherol
      may protect LDL against peroxidative modification, maintaining its ability to act
      as a ligand for LDL receptors in vivo.

PMID- 9919490
TI  - Effects of iron and copper supplementation on the formation of thiobarbituric
      acid-reactive substances and phosphatidylcholine hydroperoxide in the livers of
      iron- and copper-deficient rats.
AB  - Free radicals and lipid peroxide formation are related to tissue damage. This
      damage is thought to be associated with various diseases. To accurately assess
      the degree of lipid hydroperoxidation in biological materials, three different
      thiobarbituric acid (TBA) assay methods and the measurement of
      phosphatidylcholine hydroperoxide (PCOOH) by the chemiluminescence-HPLC (CL-HPLC)
      method were compared. Iron and copper deficiencies in rats reduced the contents
      of these metals. The addition of iron and copper to liver homogenates produced
      dose-dependent increases and decreases in TBARS, respectively. TBARS measured by
      the Shinnhuber method slightly increased with the addition of copper. The
      measurement of PCOOH was less affected by the addition of these metals. TBARS did
      not reflect lipid peroxidation when different concentrations of metals were
      present in the samples. The TBARS level is thus not a suitable marker for the
      assess of lipid peroxidation. PCOOH, accumulated as a primary peroxidation
      product from membrane phospholipids in the liver, was found to be a more
      appropriate marker for the estimating hepatic lipid peroxidation in the iron-
      and/or copper-deficient condition.

PMID- 9919491
TI  - Reciprocal effects of dietary sesamin on ketogenesis and triacylglycerol
      secretion by the rat liver.
AB  - The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on
      ketone body production and lipid secretion were studied in isolated perfused
      liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from
      14 to 16 d resulted in an enlargement of liver weight. Ketone body production was
      significantly elevated in the livers perfused with oleic acid in comparison with
      those perfused without an exogenous-free fatty acid, and sesamin feeding caused a
      stimulation of ketone body production, especially when exogenous oleic acid was
      provided. On the other hand, the ratio of beta-hydroxybutyrate to acetoacetate,
      an index of mitochondrial redox potential, tended to increase in the livers
      perfused with oleic acid compared with those without fatty acid, thought it was
      consistently lowered by dietary sesamin. The cumulative secretion of
      triacylglycerol, but not of cholesterol, by the livers from sesamin-fed rats was
      decreased markedly, especially when exogenous oleic acid was provided, suggesting
      an inverse relationship between the rates of ketogenesis and triacylglycerol
      secretion. These results suggest that dietary sesamin exerts its
      hypotriglyceridemic effect at least in part through an enhanced metabolism of
      exogenous-free fatty acid to oxidation at the expense of esterification in rat
      liver.

PMID- 9919492
TI  - Effect of whey hydrolysate formula on the transfer of beta-lactoglobulin into
      serum and milk in mice.
AB  - This study was performed to elucidate the effect of whey hydrolysate formula on
      the transfer of an antigen into serum and milk. The concentrations of beta
      lactoglobulin in serum and milk were positively correlated (p < 0.01). The
      concentration of beta-lactoglobulin in serum tended to become low in the mouse
      and to be accompanied with a high level of fecal anti-beta-lactoglobulin IgA
      concentration. The fecal anti-beta-lactoglobulin IgA of mice fed hydrolysate
      formula for 12 weeks was significantly higher than that of the control formula
      fed mice (p < 0.05). These results suggest that a high level of intestinal IgA
      elicited by the feeding of hydrolysate formula may reduce the transfer of beta
      lactoglobulin into serum and milk.

PMID- 9919493
TI  - Alliances and school-based health care.

PMID- 9919494
TI  - School-based health centers in the context of education reform.
AB  - The rapid proliferation of school-based health centers is taking place at the
      same time that school systems are seeking to improve their educational practices.
      Many different school reform models are being promulgated with modest success.
      Absence of connections between school reorganization and the provision of human
      services may lead to failure. The emerging community school model integrates
      quality education with effective health, mental health, and social services in
      "one stop" school centers that become student, parent, and community hubs.

PMID- 9919495
TI  - School-based health centers and school nurses: cementing the collaboration.
AB  - As school health personnel respond to the changing needs of children, new models
      are being developed and traditional models are being reexamined. The role of the
      school nurse is expanding at the same time as school-based health centers are
      increasing in number. Partnerships between school-based health centers and school
      nurses are critical for the success of school-based health centers, and
      partnerships will enhance and expand roles for school nurses. This paper
      clarifies the role of each in three areas: collaboration, communication, and
      cooperation. In addition, obstacles to partnerships are examined. The goal of
      this collaboration is a shared vision for the continuum of school health services
      in which school nurse and school health center serve integral roles. Elements for
      successful collaboration between nurse and health center are reviewed, including
      clarifying roles, shared leadership and program ownership, cooperative training
      and continuing education, negotiating conflict, and most importantly, maintaining
      mutual support and respect.

PMID- 9919496
TI  - Interdisciplinary collaborative training for school-based health professionals.
AB  - Changes in the nation's health and education systems have mandated that
      disciplines work together in a coordinated and collaborative manner to meet the
      complex health and educational needs of children and adolescents. This need for
      interdisciplinary collaborative training becomes even more of an issue for
      professionals providing services in school-based health centers. Although several
      foundation projects have focused on training health care professionals and other
      service disciplines, there are relatively few reports of interdisciplinary
      training of school health professionals. Two projects--the California State
      University Interprofessional Collaboration Training Project and the Catholic
      University of America School Nurse Practitioner Program--are reviewed and
      suggestions are presented for expanding interdisciplinary training of school
      based health professionals in academic institutions.

PMID- 9919497
TI  - Optimizing the roles of school mental health professionals.
AB  - Each mental health discipline offers unique contributions to the development and
      operation of school-based mental health programs. The collaboration of
      professionals from different disciplines with each other, as well as with health
      and educational staff, is essential for service delivery in school settings.
      Conversely, interprofessional conflicts and turf issues can impede the
      development of effective school-based mental health programs. The authors, who
      represent counseling, nursing, psychiatry, psychology, and social work, discuss
      the roles and competencies of each profession in providing school-based mental
      health services. Training requirements within each discipline that relate to
      school mental health are described. Barriers to effective interdisciplinary
      collaboration, and methods of overcoming them, are delineated.

PMID- 9919498
TI  - Family involvement in expanded school mental health.
AB  - Expanded school mental health (ESMH) programs address the limitations of
      traditional mental health agencies in meeting the needs of youth by providing a
      full range of services in a familiar and nonstigmatizing setting. Because of the
      central role families play in the lives of children, their involvement in ESMH
      can enhance the effectiveness of treatments and ensure that services are
      responsive to the needs of the larger community. Increasing family involvement,
      however, is a complex and resource-intensive endeavor, and requires consideration
      of the goals of the ESMH program and potential obstacles to meeting those goals.
      The challenges of involving family members in ESMH, guidelines for determining
      the program's goals with respect to family involvement, and strategies for
      achieving these goals are described. Underlying the strategies is the need to be
      flexible, creative, and respectful of the beliefs and concerns of the families
      served by the ESMH program.

PMID- 9919499
TI  - Business and faith: key community partnerships for school-based health centers.
AB  - School-based health centers need to form partnerships with organizations in the
      community. These relationships are essential to the viability of the centers
      because they can provide support and resources. However, benefits should be
      accrued by all partners, not just the health centers. Although there are many
      communities for school-based health centers to connect to, this article focuses
      on two integral ones--communities of business and faith. Key findings from a
      project formed to develop communication strategies and to generate support from
      the business community are reviewed. Recommendations for school-based health
      centers in approaching the business community are provided. Similarities and
      differences between communities of faith and strategies of develop relationships
      with these communities are presented. School-based health centers are encouraged
      to understand the characteristics and priorities of their partners in communities
      of business and faith, and to pursue strong relationships with both communities.

PMID- 9919500
TI  - Managed care, school health programs, and adolescent health services:
      opportunities for health promotion.
AB  - The rapid expansion of managed care creates opportunities and dilemmas for those
      involved in school health and adolescent health promotion. Managed care
      organizations (MCOs), public health agencies, and school and adolescent health
      providers share certain common goals and priorities including an emphasis on
      prevention, cost-effectiveness, and quality of care--and a willingness to explore
      innovative approaches to health promotion and disease prevention. However, MCOs
      often face conflicting challenges, balancing the goals of cost containment and
      investment in prevention. In considering support for school health programs, MCOs
      will be interested in evidence about the effectiveness of services in improving
      health and/or reducing medical expenditures. Mechanisms for improving prevention
      efforts within MCOs include quality assurance systems to monitor the performance
      of health plans, practice guidelines from professional organizations, and the
      contracting process between payers and health care providers. Development of
      partnerships between MCOs and schools will be a challenge given competing
      priorities, variation in managed care arrangements, structural differences
      between MCOs and schools, and variability in services provided by school health
      programs.

PMID- 9919501
TI  - The new child health insurance expansions: how will school-based health centers
      fit in?
AB  - In June 1998, the Making the Grade National Program Office and the National
      Assembly on School-Based Health Care sponsored a workshop on the relationship
      between the State Child Health Insurance Program (SCHIP) and school-based health
      centers. Workshop participants used the health centers' experience with Medicaid
      managed care as a window for understanding their prospects for negotiating
      contracts with health plans under SCHIP. Speakers representing the federal
      perspective, state agencies, health plans, and local school-based health centers
      offered their views on the challenges of developing contracts, incentives, and
      disincentives that health plans have to contract with school-based health
      centers, and what has accounted for success where relationships are moving
      forward. Experiences in Colorado and Connecticut were presented as case studies
      on these evolving issues.

PMID- 9919502
TI  - Mass spectrometric quantification of F2-isoprostanes in biological fluids and
      tissues as measure of oxidant stress.
AB  - This chapter has outlined methods to assess lipid peroxidation associated with
      oxidant injury in vivo by quantifying concentrations of free F2-IsoPs in
      biological fluids and levels of F2-IsoPs esterified in tissue lipids. The mass
      spectrometric assay described herein is highly precise and accurate. A potential
      shortcoming with this approach is that it requires expensive instrumentation,
      i.e., a mass spectrometer. However, several immunoassays for an F2-IsoP, 8-iso
      PGF2 alpha, have become available from commercial sources. At this time, the
      accuracy and reliability of these assay for quantifying F2-IsoPs in biological
      fluids has not been fully validated by mass spectrometry. If these immunoassays
      prove to be a reliable measure of F2-IsoPs, however, this should greatly expand
      the use of F2-IsoPs to assess oxidant stress. In conclusion, studies carried out
      over the past several years have shown that measurement of F2-IsoPs has overcome
      many of the limitations associated with other methods to assess oxidant status,
      especially when applied to the measurement of oxidant stress in vivo in humans.
      Therefore, the quantification of F2-IsoPs represents an important advance in our
      ability to assess the role of oxidant stress and lipid peroxidation in human
      disease.

PMID- 9919503
TI  - Gas chromatography-mass spectrometry assay for measurement of plasma
      isoprostanes.

PMID- 9919504
TI  - Preparation of lipid hydroperoxide-free low-density lipoproteins.

PMID- 9919505
TI  - Lipid hydroperoxide analysis by high-performance liquid chromatography with
      mercury cathode electrochemical detection.
AB  - In addition to the applications described, HPLC-EC(Hg) can be used for
      determining LOOHs in lipoproteins and for monitoring LOOH detoxification in
      cells. As it continues to be developed and refined, this approach should prove to
      be valuable not only for ultrasensitive determination of lipid-derived peroxides,
      but protein- and nucleic acid-derived peroxided as well.

PMID- 9919506
TI  - Measurement of lipid hydroperoxides in human plasma and lipoproteins by kinetic
      analysis of photon emission.

PMID- 9919507
TI  - High-performance liquid chromatography analysis of cholesterol linoleate
      hydroperoxide in oxidized low density lipoproteins: calibration by conjugated
      diene internal standard.
AB  - The cholesterol linoleate hydroperoxides formed in LDL after oxidant stress are
      measured by HPLC, with UV detection at 234 nm. Calibration is performed with a
      conjugated diene internal standard. This internal standard is synthesized by the
      transesterification of the methyl ester of conjugated diene linoleic acid with a
      long-chain alcohol, such as arachidyl alcohol (C20). Different long-chain
      alcohols can be used during the transesterification, to achieve internal
      standards with variable HPLC retention times. The method allows measurement of
      cholesterol linoleate hydroperoxide in LDL very early during attack with Cu2+ or
      other initiator, so that the kinetics of antioxidant loss and hydroperoxide
      formation can be concurrently monitored.

PMID- 9919508
TI  - Determination of phospholipid oxidation in cultured cells.

PMID- 9919509
TI  - Ferrous ion oxidation in presence of xylenol orange for detection of lipid
      hydroperoxides in plasma.

PMID- 9919510
TI  - Purification and characterization of phospholipid for use in lipid oxidation
      studies.

PMID- 9919511
TI  - Assay of malondialdehyde and other alkanals in biological fluids by gas
      chromatography-mass spectrometry.
AB  - The method described in this chapter allows the accurate measurement of MDA in
      diverse biological samples and can be extended to measurements of other alkanals.
      The use of GC/MS-NCI ensures specificity and sensitivity, and the ability to
      prepare samples without heating limits oxidation artifact. Although the widely
      used TBA assay for MDA does not require sophisticated equipment, its results may
      be of limited value as the assay is hindered by the possibility of cross
      reactivity and by heat-induced oxidation artifact. This GC-MS technique offers
      the additional advantages of efficient processing of large numbers of samples and
      the elimination of recovery errors by inclusion of an internal standard.

PMID- 9919512
TI  - Assessment of physiological interaction between vitamin E and vitamin C.

PMID- 9919513
TI  - Modification of proteins and lipids by myeloperoxidase.

PMID- 9919514
TI  - Protein carbonyl measurement by enzyme-linked immunosorbent assay.

PMID- 9919515
TI  - Detection of 3-chlorotyrosine in proteins exposed to neutrophil oxidants.

PMID- 9919516
TI  - Determination of 2-oxohistidine by amino acid analysis.

PMID- 9919517
TI  - Detecting oxidative modification of biomolecules with isotope dilution mass
      spectrometry: sensitive and quantitative assays for oxidized amino acids in
      proteins and tissues.

PMID- 9919518
TI  - Measurement of protein carbonyls in human brain tissue.

PMID- 9919519
TI  - 8-Hydroxydeoxyguanosine and 8-hydroxyguanine as biomarkers of oxidative DNA
      damage.

PMID- 9919520
TI  - Markers of oxidative damage to DNA: antioxidants and molecular damage.

PMID- 9919521
TI  - Comet assay for nuclear DNA damage.

PMID- 9919522
TI  - Generation of hydroxyl radical by photolysis of mercaptopyridine N-oxides:
      application to redox chemistry of purines.

PMID- 9919523
TI  - Trace determination of hydroxyl radical using fluorescence detection.

PMID- 9919524
TI  - Isoforms of mammalian peroxiredoxin that reduce peroxides in presence of
      thioredoxin.

PMID- 9919525
TI  - Preparation and assay of mammalian thioredoxin and thioredoxin reductase.

PMID- 9919527
TI  - Determination of tissue susceptibility to oxidative stress by enhanced
      luminescence technique.

PMID- 9919526
TI  - Methionine sulfoxide reductase in antioxidant defense.

PMID- 9919528
TI  - Measurement of hydroxyl radical by salicylate in striatum of intact brain.

PMID- 9919529
TI  - Analytical and numerical techniques for evaluation of free radical damage in
      cultured cells using imaging cytometry and fluorescent indicators.

PMID- 9919530
TI  - In vivo measurement of hydrogen peroxide by microelectrode.

PMID- 9919531
TI  - Overall low molecular weight antioxidant activity of biological fluids and
      tissues by cyclic voltammetry.

PMID- 9919532
TI  - Estimation of hydroxyl free radical levels in vivo based on liquid chromatography
      with electrochemical detection.

PMID- 9919533
TI  - Mechanism of interaction of in situ produced nitroimidazole reduction derivatives
      with DNA using electrochemical DNA biosensor.

PMID- 9919534
TI  - Heme oxygenase activity determination by high-performance liquid chromatography.

PMID- 9919535
TI  - Assay for redox-sensitive kinases.

PMID- 9919537
TI  - Nuclear factor kappa B activity in response to oxidants and antioxidants.
AB  - The goal of this chapter was to review the current protocols that are available
      to measure the activation of NF-kappa B. The methods discussed all have their
      pitfalls when used in isolation. To obtain meaningful information, nuclear
      translocation and transcriptional activation should be studied in conjunction.
      Study of NF-kappa B regulated protein expression is the most physiologically
      relevant approach to monitoring the transcription regulatory effect of NF-kappa
      B. Because of the limitations of transcriptional analysis in primary cell
      cultures or tissues, incorporation of multiple approaches is recommended when the
      involvement of NF-kappa B in a disease process is evaluated.

PMID- 9919536
TI  - Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome.
AB  - It is becoming increasingly apparent that NF-kappa B plays a critical role in
      regulating the inflammatory response. Data obtained from studies in our
      laboratories demonstrate that the proteasome plays an important role in the
      inflammatory cascade by regulating the activation of NF-kappa B. Indeed, the
      availability of selective and orally active proteasome inhibitors should prove
      useful in delineating the roles of the proteasome and NF-kappa B in other
      pathophysiological conditions such as cancer and heart disease.

PMID- 9919538
TI  - Assessing induction of I kappa B by nitric oxide.

PMID- 9919539
TI  - Nitrosative stress.

PMID- 9919540
TI  - Determination of cell-cell adhesion in response to oxidants and antioxidants.

PMID- 9919541
TI  - Antioxidant regulation of gene expression: analysis of differentially expressed
      mRNAs.

PMID- 9919542
TI  - Noninvasive measurement of alpha-tocopherol gradients in human stratum corneum by
      high-performance liquid chromatography analysis of sequential tape strippings.

PMID- 9919543
TI  - Ultraweak photon emission of human skin in vivo: influence of topically applied
      antioxidants on human skin.

PMID- 9919544
TI  - Noninvasive in vivo evaluation of skin antioxidant activity and oxidation status.
AB  - The method described here allows noninvasive quantification of reducing LMWA or
      the lipid hydroperoxide present on the surface of the skin. Quantification of
      reducing antioxidants can be achieved because they are secreted from the skin
      surface into a well containing an extraction solution. Analysis of the reducing
      equivalents released indicates the presence of uric acid and ascorbic acid. Other
      LMWA released from the skin are as yet unidentified. The secretion of the LMWA
      reaches a plateau following 20-30 min of incubation. Therefore, a 30-min
      incubation period was chosen as the optimal time for the extraction solution to
      be present in the well and in contact with the skin. This extraction procedure
      can be repeated after 24 hr. This period of time is needed for regeneration of
      the LMWA to their initial levels. Direct measurement allows continuous
      determination of the release of LMWA and their interaction with the iron chelate.
      The reaction is completed after 25-35 min, at which time the final potential can
      be recorded. When organic peroxides on the surface of the skin are determined, it
      is important that the glassy carbon electrode be in close contact with the skin,
      since the reaction occurs on the surface of the electrode and the bound peroxide
      on the outer layer of the skin. Furthermore, close contact is needed to avoid
      interference of reducing equivalents secreted from the skin into the well.

PMID- 9919546
TI  - Clinical use of photoionization gas chromatography for detection of lipid
      peroxidation.

PMID- 9919545
TI  - Antioxidative homeostasis: characterization by means of chemiluminescent
      technique.

PMID- 9919547
TI  - Intravital fluorescence microscopy for the study of leukocyte interaction with
      platelets and endothelial cells.

PMID- 9919548
TI  - Quantifying role of nitric oxide in endothelial barrier regulation.

PMID- 9919549
TI  - In vivo measurements of endothelial cell adhesion molecule expression.
AB  - The essential role of endothelial CAMs in the recruitment of leukocytes to sites
      of inflammation has been extensively studied in recent years. The development of
      techniques such as the radiolabeled MAb method that is described in this chapter
      has enabled investigators to quantitatively assess the expression of endothelial
      CAMs in different regional vascular beds. Although the study of adhesion
      molecules in vitro has extended our knowledge of the mechanisms and mediators of
      endothelial CAM function, the newly acquired in vivo data would indicate that
      findings resulting from experiments on monolayers of cultured endothelial cells
      may not accurately depict inflammatory events that occur in vivo. Thus,
      additional work is needed to more fully define the conditions that account for
      the discrepencies noted between the in vivo and in vitro models of endothelial
      CAM expression.

PMID- 9919550
TI  - Ruthenium red as measure of mast cell activation.

PMID- 9919551
TI  - Quantitation of protein-bound 3-nitrotyrosine by high-performance liquid
      chromatography with electrochemical detection.
AB  - HPLC with electrochemical detection of the N-acetylated, dithionite-reduced
      derivative of NTyr provides a highly sensitive and selective means of measuring
      this nitrated residue in biological samples. The detection of protein-bound NTyr
      at baseline levels of approximately < or = 1 mumol per mole Tyr indicates that in
      plasma or total cellular extracts, endogenous nitration of tyrosine residues is
      low. This baseline level of NTyr and the marked increases that are observed
      during inflammatory conditions opens up the opportunity to observe more subtle
      changes in tyrosine nitration, thus broadening the range of studies that can be
      performed using this biomarker. This analytical approach may allow one to
      estimate protein nitration in an animal or individual exposed to elevated levels
      of peroxynitrite or other reactive nitrogen oxides, and it may assist in the
      evaluation of factors that contribute to this potentially important amino acid
      modification. Furthermore, this assay may allow one to assess the potential
      benefits of interventions that may limit nitration reactions in vivo.

PMID- 9919552
TI  - Quantitative estimation of endogenous N-nitrosation in humans by monitoring N
      nitrosoproline in urine.

PMID- 9919554
TI  - Nitric oxide and superoxide detection in human platelets.

PMID- 9919553
TI  - Measuring nitric oxide production in human clinical studies.

PMID- 9919555
TI  - Assay of isoforms of Escherichia coli-expressed nitric oxide synthase.
AB  - The techniques described herein have added to our repertoire of experimental
      approaches for the characterization of the NOSs. These procedures have reinforced
      our conviction that the NOSs are structurally suited to perform unique functions
      in their cellular milieux and that these differences have physiological
      consequences.

PMID- 9919556
TI  - Identification of carrier systems in plasma membranes of mammalian cells involved
      in transport of L-arginine.

PMID- 9919557
TI  - Measurement of nitric oxide synthesis in humans using L-[15N2]arginine.

PMID- 9919558
TI  - Concerted nitric oxide/oxygen delivery by hemoglobin.

PMID- 9919559
TI  - Scintillation proximity assay to measure nitroarginine and tetrahydrobiopterin
      binding to heme domain of neuronal nitric oxide synthase.

PMID- 9919560
TI  - Measurement of nitric oxide-mediated effects on zinc homeostasis and zinc finger
      transcription factors.

PMID- 9919561
TI  - Immunoprecipitation of nitrotyrosine-containing proteins.

PMID- 9919562
TI  - Gel electrofocusing method for studying protein S-nitrosylation.

PMID- 9919563
TI  - Measurement and significance of free and protein-bound 3-nitrotyrosine, 3
      chlorotyrosine, and free 3-nitro-4-hydroxyphenylacetic acid in biologic samples:
      a high-performance liquid chromatography method using electrochemical detection.

PMID- 9919564
TI  - Determination of nitric oxide saturated solution by amperometry on modified
      microelectrode.

PMID- 9919565
TI  - Electron spin resonance spin-trapping detection of superoxide generated by
      neuronal nitric oxide synthase.
AB  - NOS is a ubiquitous enzyme that has an oxygenase and reductase activity. NOS
      reduces electron acceptors, at the reductase domain, by a one-electron mechanism
      that is not inhibited by SOD. One example of this activity is the direct
      reduction of ferricytochrome c by nNOS. Redox cycling electron acceptors (EA in
      Scheme 1), such as lucigenin and NBT, are reduced by NOS to generate an
      intermediate radical (EAred). This radical can then be reoxidized to the parent
      compound by oxygen, and in the process generate superoxide. Consequently, both
      NBT and lucigenin will enhance NADPH-dependent superoxide generation in the
      presence of flavoprotein reductases such as NOS. The artificial generation of
      superoxide from lucigenin and NBT is a major pitfall in the use of these
      compounds as superoxide probes. We conclude that the use of ESR spin-trapping
      techniques, although not free of problems, is a viable technique for the
      detection and quantification of superoxide in systems containing nNOS.

PMID- 9919566
TI  - Direct and simultaneous ultraviolet second-derivative spectrophotometric
      determination of nitrite and nitrate in preparations of peroxynitrite.
AB  - We have determined the initial concentrations of nitrite and nitrate for three
      different methods of synthesizing peroxynitrite using an ultraviolet second
      derivative spectroscopy method (Fig. 3). As expected, the net nitrogen balance in
      these preparations (Fig. 4) and the yields of nitrite and nitrate (Table II)
      indicate that, at pH 6.0, peroxynitrite decomposes to give essentially NO3-.
      Stock solutions of peroxynitrite prepared using method I (ozonation of azide)
      consistently contain more NO2- and NO3- than method II (isoamyl nitrite with
      hydrogen peroxide) and method III (hydrogen peroxide with nitrous acid). Method
      II gives the least amount of NO2- contaminants, and NO3- impurities are the
      lowest in method III (Table I).

PMID- 9919567
TI  - Regulation of mitochondrial respiration by adenosine diphosphate, oxygen, and
      nitric oxide.

PMID- 9919568
TI  - Detection of S-nitrosothiols by fluorometric and colorimetric methods.

PMID- 9919569
TI  - Chemical approaches toward generation of nitroxyl.

PMID- 9919570
TI  - Stability of S-nitrosothiols in presence of copper, zinc-superoxide dismutase.

PMID- 9919571
TI  - Fluorometric detection of S-nitrosothiols.

PMID- 9919572
TI  - Redox-sensitive nitric oxide donors: nitric oxide generation through
      electrolysis.

PMID- 9919573
TI  - Glyco-S-nitrosothiols: sugar-SNAP, a new type of nitric oxide donor.

PMID- 9919574
TI  - Protein S-nitrosating agents.
AB  - A series of peptidyl N-nitrosoanilines were designed, synthesized, and evaluated
      as inactivators of cysteine protease papain. These new compounds exhibited
      different inhibitory activities toward cysteine protease papain in a time- and
      concentration-dependent manner with second-order rate constants (ki/KI) ranging
      over two orders of magnitude from 0.604 M-1 sec-1 (1) to 100.36 M-1 sec-1 (7).
      Formation of the S-NO bond in papain is corroborated by evidence obtained from
      spectroscopic analyses. The fact that S-nitrosylated enzyme can regain its
      activity upon addition of thiol compounds such as glutathione makes this class of
      compounds suitable as templates for the development of potent reversible and
      covalent cysteine protease inhibitors.

PMID- 9919575
TI  - Measurement of nitrite and nitrate by high-performance ion chromatography.

PMID- 9919576
TI  - Iron diethyldithiocarbamate as spin trap for nitric oxide detection.

PMID- 9919577
TI  - Synthesis, chemistry, and applications of nitroxyl ion releasers sodium
      trioxodinitrate or Angeli's salt and Piloty's acid.

PMID- 9919578
TI  - Nitric oxide donor generation from reactions of peroxynitrite.

PMID- 9919579
TI  - Defenses against peroxynitrite.

PMID- 9919580
TI  - Use of repair endonucleases to assess DNA damage by peroxynitrite.

PMID- 9919581
TI  - Interaction of carotenoids and tocopherols with peroxynitrite.

PMID- 9919582
TI  - Assessment of peroxynitrite scavengers in vitro.

PMID- 9919583
TI  - Peroxynitrite studied by stopped-flow spectroscopy.

PMID- 9919584
TI  - Peroxynitrite reactions with carbon dioxide-bicarbonate.

PMID- 9919585
TI  - Detection of reactive nitrogen species using 2,7-dichlorodihydrofluorescein and
      dihydrorhodamine 123.

PMID- 9919586
TI  - Immunohistochemical methods to detect nitrotyrosine.
AB  - The immunohistochemical detection of nitrotyrosine is a robust method for
      detecting peroxynitrite and other reactive nitrogen species. Success depends on
      optimizing conditions for the particular tissue and experimental design under
      investigation and the use of positive and negative controls to verify
      specificity. The two controls of dithionite reduction and blocking with
      nitrotyrosine are a powerful combination to demonstrate specificity. The
      pathological significance of tyrosine nitration in proteins can also be
      approached. Generally, nitrated proteins can be isolated from diseased tissues by
      immunoprecipitation and Western blotting. The sites of nitration on specific
      proteins can be determined by mass spectrometry, which has revealed surprising
      specificity in which tyrosines and/or proteins are nitrated in vivo. This
      provides important evidence concerning the functional consequences of
      peroxynitrite formation in vivo.

PMID- 9919587
TI  - Mitochondria, nitric oxide, and peroxynitrite.

PMID- 9919588
TI  - Examining apoptosis in cultured cells after exposure to nitric oxide and
      peroxynitrite.

PMID- 9919589
TI  - Application of authentic peroxynitrite to biological materials.
AB  - A method to expose cultured cardiac myocytes to authentic ONOO- by using a
      constant perfusion system was described. The perfusion apparatus is linked to a
      microscope equipped with video and fluorescence measurement systems, which enable
      the evaluation of myocardial contraction, [Ca2+]i, [pH]i, and membrane fluidity.
      Special care is needed to adjust the pH of the solution appropriately and to
      obtain a constant concentration of ONOO-.

PMID- 9919591
TI  - Assay of antioxidant and antiinflammatory activity of nitric oxide in vivo.

PMID- 9919590
TI  - Antioxidant effects of nitric oxide.

PMID- 9919592
TI  - Effects of nitric oxide on iron or hemoprotein-catalyzed oxidative reactions.

PMID- 9919593
TI  - Antioxidant effects of nitric oxide and nitric oxide donor compounds on low
      density lipoprotein oxidation.
AB  - Nitric oxide, when slowly released from a donor compound, has a potent inhibitory
      effect on the oxidative modification of LDL. This can be studied by monitoring
      changes in the lipid, protein, and antioxidant components of the LDL particle. In
      addition, the kinetics of LDL oxidation provides an insight into the mechanistic
      basis of the nitric oxide-dependent inhibition of LDL oxidation.

PMID- 9919594
TI  - Nitration of unsaturated fatty acids by nitric oxide-derived reactive species.
AB  - Reactions of linoleate (and presumably other unsaturated fatty acids) with
      reactive nitrogen species that form in biological systems from secondary
      reactions of .NO yield two main nitration product groups, LNO2 (formed by ONOO-,
      .NO2, or NO2+ reaction with linoleate), and LONO2 (formed by HONO reaction with
      13(S)-HPODE, or .NO termination with LOO.). Comparison of HPLC retention times
      and m/z for lipid nitration products indicate that the mechanisms of nitrated
      product formation converge at several points: (i) The initial product of HONO
      attack on LOOH will be LOONO, which is identical to the initial termination
      product of LOO. reaction with .NO. (ii) Dissociation of LOONO to give LO. and
      .NO2 via caged radicals, which recombine to give LONO2 (m/z 340) will occur,
      regardless of how LOONO is formed (Fig. 7). (iii) In some experiments, the
      reaction of O2- (where oxidation is initiated by xanthine oxidase-derived O2-
      production and metal-dependent decomposition of H2O2) with .NO will result in
      generation of ONOO-. Nitration of unsaturated lipid by this species will yield a
      species demonstrated herein to be LNO2. Lipid oxidation leads to formation of
      bioactive products, including hydroxides, hydroperoxides, and isoprostanes. In
      vivo, nitrated lipids (LNO2, LONO2) may also possess bioactivity, for example
      through eicosanoid receptor binding activity, or by acting as
      antagonists/competitive inhibitors of eicosanoid receptor-ligand interactions. In
      addition, nitrated lipids could mediate signal transduction via direct .NO
      donation, transnitrosation, or following reductive metabolism. Similar bioactive
      products are formed following ONOO- reaction with glucose, glycerol, and other
      biomolecules.

PMID- 9919595
TI  - Analysis of aromatic nitration, chlorination, and hydroxylation by gas
      chromatography-mass spectrometry.

PMID- 9919596
TI  - Products from reaction of peroxynitrite with gamma-tocopherol.

PMID- 9919597
TI  - Nitric oxide radical scavenging of flavonoids.

PMID- 9919598
TI  - Assay of inducible form of nitric oxide synthase activity: effect of flavonoids
      and plant extracts.

PMID- 9919599
TI  - In vitro system to study role of blood flow on nitric oxide production and cell
      signaling in endothelial cells.
AB  - Through the approaches illustrated in this article we have demonstrated how
      molecular signaling events can be elucidated in cells responding to physiological
      forces. With the recent findings that endothelial form of nitric oxide synthase
      is associated with proteins such as caveolin and the availability of these cDNA
      constructs, this methodology allows a possible avenue to determine the
      physiological significance of such associations and the regulation of NO
      formation in response to shear stress.

PMID- 9919601
TI  - Fluorescence detection of nitric oxide based on cheletropic spin traps.

PMID- 9919600
TI  - Pharmacological approaches of endothelial nitric oxide-dependent vasorelaxation
      induced by polyphenols from plant extracts.

PMID- 9919602
TI  - [Attitudes of Polish occupational medicine physicians towards a proposal of
      requirements for occupational medicine training in Europe].
AB  - In order to determine key competences required of occupational medicine
      specialists, common throughout Europe, a questionnaire has been developed and
      distributed among several European countries. The questionnaire contained 115
      subjects related to 8 fields of activities carried out by occupational medicine
      physicians (occupational hazards to health, assessment of disability and fitness
      for work, communications, research methods, management, environmental medicine,
      occupational health law and ethics, and health promotion). In each of these
      fields, competences were classified into three following categories: knowledge,
      experience and skills. Respondents were asked to allocate a score from 0 to 5 for
      each subject, where 0 = not necessary; 1 = of minimum importance, and 5 = most
      important or essential. In Poland the questionnaire was distributed among two
      groups of specialists: group I--experienced specialists in occupational medicine
      (leading representatives of occupational health care management), and group II-
      relatively younger and less experienced occupational medicine physicians,
      participating in the specialist training, organised by The Nofer Institute of
      Occupational Medicine. A comprehensive analysis of the completed questionnaires
      was carried out in two dimensions: substantive (the importance of individual
      competences as perceived by Polish specialists in occupational medicine), and
      comparative (evaluation and interpretation of similarities and differences
      between two groups of respondents). A hierarchy of requirements, occupational
      medicine training in Poland is to satisfy, was reconstructed with two sets of
      competences, one recognised by respondents as needless and the other recognised
      as useful with different grades of importance. Some characteristic differences in
      opinions between two groups studies were highlighted.

PMID- 9919603
TI  - [The use of biological monitoring in the assessment of occupational exposure to
      styrene in fiberglass-reinforced plastics industry].
AB  - A field study was carried out in order to investigate the effect of occupational
      exposure to styrene on the urinary excretion of mandelic and phenylglyoxylic
      acids (MA and PGA). Over a period of three years, 210 periodical, prophylactic
      examinations were performed on 66 fiberglass-reinforced plastics workers. The
      examinations embraced environmental and biological monitoring, which involved the
      measurement of styrene concentration in the air and the excretion rate of urinary
      MA and PGA. An eight-hour time-weighed average (MAC) exposure values ranged from
      16.1 to 246 mg/m3 (mean: 76.1 mg/m3). The average urinary excretion rates of MA
      and PGA were 17.7 (1-202) and 28.8 (2-267) mg/h, respectively. The measurements
      of MA excretion rate were compared with the measurements of styrene concentration
      in the air. It seems advisable to investigate whether the recommended biological
      limits value of 16 mg/h for mandelic acid is not too high in view of the binding
      OEL value of 50 mg/m3 for styrene.

PMID- 9919604
TI  - [Early neuropsychological dysfunctions in workers exposed to benzene and its
      homologues].
AB  - Psychological examinations using five tests of interference and four tests of
      motoric reaction were carried out in a group of 28 men occupationally exposed to
      mixtures of benzene, toluene and xylene compounds. The examinations indicated
      diminished function of the cortical associative centre, excessive susceptibility
      to stimuli disturbing psychic processes slowing of the orientation ability and
      motor reaction time. Tests of habitual interference, reaction time to visual
      stimuli and Ricossay's test proved to be most useful in the detection of early
      psychic dysfunctions.

PMID- 9919605
TI  - [Skin reactivity in subjects sensitive to different concentrations of nickel,
      chromium and cobalt].
AB  - Patch tests with serial dilutions of nickel sulphate, potassium dichromate and
      cobalt chloride in petrolatum were performed on 124 nickel-sensitive, 64 chromium
      sensitive, and 72 cobalt-sensitive subjects. The lowest eliciting patch test
      concentrations were as follows: nickel sulphate--0.005, potassium dichromate-
      0.0025, and cobalt chloride--0.005.

PMID- 9919607
TI  - [Multiple chemical sensitivity: a new type of toxicity?].
AB  - Multiplechemical sensitivity (MCS) is a chronic condition manifested by the
      appearance of variable symptoms, involving many systems and organs, after
      exposure to extremely low levels of chemicals, mainly pesticides and solvents.
      The paper discusses briefly the main hypotheses concerning causes and mechanisms
      of MCS development. It was emphasized that during neurotoxicity assessment is
      necessary to pay more attention to these aspects of toxic effects of chemicals
      likely to generate MSc.

PMID- 9919606
TI  - [Urinary cotinine as a biomarker of exposure to tobacco smoke].
AB  - Several markers are used to monitor active or passive exposure to tobacco smoke.
      They include measurements of carboxyhaemoglobin in the blood, carbon dioxide in
      the expired air, thiocyanates and nicotine in the saliva, plasma (serum) or
      urine. The determination of cotinine, the main nicotine metabolite, in biological
      fluids is a biomarker which finds still wider application. This metabolite can be
      determined in the urine and saliva and plasma. Cotinine, as a biomarker of
      exposure to tobacco smoke, is used in epidemiological studies aimed to find out
      to what extent the exposure to occupational harmful factors affects the workers'
      health. The application of this biomarker helped to classify workers more
      effectively into smokers and non-smokers, and to provide better conditions for
      finding out whether other non-occupational factors such as smoking do not
      confound the evaluation of health threats induced by work-related hazards.

PMID- 9919608
TI  - [The evaluation of mean indoor concentration of radon based on the measurement of
      210Pb concentration in glass].
AB  - An average dose received by an inhabitant of the terrestrial globe from all
      natural sources of ionizing radiation occurring in the nature accounts for 2.6
      mSv annually. Nearly 50 of this dose comes from radon and products of its
      decomposition which accumulate in our dwellings. Bearing in mind changes in radon
      concentrations over the time it would be advisable to develop a method for the
      evaluation of mean long-term concentrations of radon. Such an evaluation can be
      carried out by measuring the amount of 210Pb implanted in glass. These
      measurements are most frequently performed by means of ionization chambers or
      trace detectors which record the number of alpha particles produced by 210Pb
      decomposition.

PMID- 9919609
TI  - [The influence and sources of infrasound: review of literature].
AB  - This paper presents a short review of infrasound sources and effects on humans.

PMID- 9919610
TI  - [The role of public health schools in the training of occupational medicine
      specialists in the United States of America].
AB  - The author addresses some aspects of specialist training of occupational medicine
      physicians in the United States of America, and discusses detailed requirements
      of the American Board of Preventive Medicine that have to be satisfied by a
      physician, specialising in this field in order to obtain the title of a
      specialist in occupational and environmental medicine. The role of Schools of
      Public Health in the process of specialist training, and some new opportunities
      and organisational solutions offered by these Schools are presented. A residency
      training programme offered by an accredited School of Public Health, University
      of Michigan is used as an example. The number of specialised occupational
      medicine physicians, practising in the USA is given. The data indicate that
      during the last ten years the number of physicians who enter into the training
      process in this field continued to show an upward tendency. Some opinions trying
      to explain the reason for a continuous lack of occupational medicine specialists
      in the United States are also presented.

PMID- 9919611
TI  - [Computer data bases in occupational medicine and their uses].

PMID- 9919612
TI  - Preadipocytes stimulate breast cancer cell growth.
AB  - Mammary fat may affect human breast cancer development. In this study a novel
      coculture system was used to investigate stromal-epithelial cell interactions in
      vitro. The extent of differentiation of a feeder layer of 3T3-L1 preadipocytes
      affected the clonal growth of breast cancer cells under anchorage-independent
      conditions. When the feeder-layer preadipocytes were proliferating, the clonal
      growth of estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB
      231 and MDA-MB-436 cells was stimulated by 100%, 43%, and 60%, respectively. In
      contrast, after differentiation the feeder layer of mature adipocytes inhibited
      clonal growth of breast cancer cell lines by 60%. No clonal growth stimulation of
      human pancreatic (Panc-1) or prostatic (PC-3) cancer cells was noted when these
      cells were grown under identical conditions with a proliferating 3T3-L1 cell
      feeder layer. These findings suggest that proliferating preadipocytes may be
      associated with factors that specifically stimulate breast cancer cell growth.

PMID- 9919613
TI  - Expression pattern of gastrointestinal selenoproteins--targets for selenium
      supplementation.
AB  - There is experimental and epidemiological evidence for an association between low
      selenium levels and gastrointestinal cancer incidence, prevalence, and mortality.
      To identify targets for selenium supplementation in the human digestive tract, we
      examined mRNA expression of various selenocysteine-containing proteins in normal
      mucosa biopsy specimens. Tissue samples from the esophagus and from different
      sites of the stomach, small bowel, and colon were obtained during endoscopies of
      the upper and lower gastrointestinal tract. Northern blot analyses revealed a
      lack of cytosolic glutathione peroxidase mRNA but a differential mRNA expression
      pattern of gastrointestinal and plasma glutathione peroxidase, selenoprotein P,
      and thioredoxin reductase. Glutathione peroxidase and thioredoxin reductase
      activities were detected in the mucosa of all biopsies, but the differential
      pattern did not reflect the differential mRNA steady-state levels. In addition to
      gastrointestinal glutathione peroxidase, which was found to play a role in colon
      cancer resistance, we identified further gastrointestinal selenoproteins, which
      may be involved in gastrointestinal cell defense and cell differentiation.

PMID- 9919614
TI  - Protection by tea against UV-A + B-induced skin cancers in hairless mice.
AB  - Consumption of tea, especially green tea, has been shown to reduce the incidence
      of ultraviolet (UV)-related skin tumors in hairless mice. Because milk is added
      to much of the tea consumed in Western cultures, we have studied the effects of
      including milk in the tea consumed by hairless mice receiving simulated solar
      radiation. Under these conditions, mice consuming tea with 10% whole milk had 30%
      fewer papillomas, 50% fewer tumors, and 55% smaller lesions than mice consuming
      water. Mice consuming tea alone had fewer papillomas and tumors than mice
      consuming tea with milk; however, the difference in area affected was not
      statistically significant. In separate experiments, there was a significant dose
      response to black tea as a preventive against UV-related skin lesions, and also
      consumption of black tea was associated with a small but significant reduction in
      the incidence of papillomas in mice previously exposed to UV radiation. The
      results of these studies demonstrate that, in hairless mice, black tea can
      inhibit the formation of UV-induced skin tumors in a dose-dependent manner and,
      even with the addition of milk, can still inhibit the growth of UV-related skin
      tumors.

PMID- 9919615
TI  - Impact of weight loss, appetite, and the inflammatory response on quality of life
      in gastrointestinal cancer patients.
AB  - The relationship between weight loss, appetite, the inflammatory response, and
      quality of life in patients with advanced gastrointestinal cancer was examined.
      Height, weight, and skinfold anthropometry were measured in 119 patients. Blood
      was taken for analysis of C-reactive protein and albumin. Appetite, performance
      status, and quality of life were assessed using EuroQol EQ-5D and EORTC QLQ-C30
      questionnaires. Weight loss was > 5% (median 17.1%) of their preillness weight in
      97 patients; the remaining 22 patients were weight stable. Anthropometric
      measurements and circulating albumin concentrations were significantly lower (p <
      0.01) and circulating concentrations of C-reactive protein were significantly
      higher in the weight-losing than in the weight-stable group (p < 0.001). Appetite
      scores, performance status, and EuroQol EQ-5D and EORTC QLQ-C30 scores were also
      lower in the weight-losing group (p < 0.01). When the weight-losing cancer
      patients were divided on the basis of whether they had a marked inflammatory
      response, albumin concentrations, appetite, and Karnofsky performance status were
      significantly lower (p < 0.05) in the group with a marked inflammatory response.
      The results of the present study are consistent with weight loss, reduction of
      appetite, and an elevated inflammatory response being important related factors
      in lowering the quality of life of gastrointestinal cancer patients.

PMID- 9919616
TI  - Polyphenols inhibit promotional phase of tumorigenesis: relevance of superoxide
      radicals.
AB  - Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA)
      offer considerable promise as anticarcinogens. The role of these dietary
      polyphenols was investigated in the promotional phase of carcinogenesis. Topical
      application of polyphenols simultaneously with phorbol-12-myristate-13-acetate
      (PMA) or mezerein resulted in significant protection against 7,12-dimethyl
      benz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most
      effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine
      peritoneal macrophages with the tumor promoters resulted in stimulation of
      superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid
      were stronger inhibitors of PMA- and mezerein-induced superoxide anion radical
      than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)
      14C]glycerol- or [methyl-14C]choline chloride-labeled resident or thioglycollate
      elicited macrophages with PMA and mezerein led to accumulation of radioactive
      diacylglycerol equivalents. The polyphenols were capable of inhibiting these
      releases.

PMID- 9919617
TI  - Role of red meat and arachidonic acid in protein kinase C activation in rat
      colonic mucosa.
AB  - Two studies were conducted to investigate the role of meat and arachidonic acid
      in colonic signal transduction, particularly protein kinase C (PKC) activation.
      In Study 1, 26 male Wistar rats were fed a casein- or a beef-based diet for four
      weeks. PKC activity was measured from the proximal and distal colonic mucosa and
      diacylglycerol concentration from fecal samples. The beef diet significantly
      increased membrane PKC activity in the proximal and distal colon and cytosolic
      PKC in the distal colon. No differences were found in fecal diacylglycerol
      concentration for the rats maintained on the two diets. In Study 2, 57 male
      Wistar rats were divided into three dietary treatment groups: a control group, a
      group supplemented with arachidonic acid at 8 mg/day (an amount equivalent to
      that available from the beef diet in Study 1), and a group supplemented with fish
      oil at 166 mg/day. After a four-week supplementation period, 6 rats per group
      were used for colonic phospholipid fatty acid analysis and 13 rats per group were
      used for analysis of colonic prostaglandin E2 concentration, sphingomyelinase,
      and PKC activities. Supplementation of dietary arachidonic acid resulted in
      incorporation of arachidonic acid into colonic phosphatidylcholine, which was
      associated with an increase in mucosal prostaglandin E2 concentration compared
      with the fish oil group. However, arachidonate supplementation had no effect on
      sphingomyelinase or PKC activities. These data indicate that meat significantly
      increases colonic PKC activity, but this effect is probably not due to the
      arachidonic acid content of meat.

PMID- 9919618
TI  - Effect of dietary vitamin E on antioxidant status and antioxidant enzyme
      activities in Sprague-Dawley rats.
AB  - The effect of dietary vitamin E on plasma, red blood cells (RBC), hepatic
      antioxidant status, and antioxidant enzyme activities was investigated. Three
      groups of six Sprague-Dawley rats were fed 0, 100, or 1,500 ppm vitamin E for
      eight weeks. Plasma alpha-tocopherol level was increased significantly by
      increasing dietary vitamin E (p < 0.05). Plasma lipid peroxidation
      (thiobarbituric acid-reactive substances) stimulation by 1 mM t-butyl
      hydroperoxide was correlated with dietary vitamin E level and was significantly
      greater in rats fed no vitamin E than in rats fed 100 or 1,500 ppm vitamin E (p <
      0.05). RBC reduced glutathione (GSH) level was positively correlated with dietary
      vitamin E and was significantly greater in rats fed 1,500 ppm vitamin E than in
      rats fed 0 or 100 ppm vitamin E (p < 0.05). RBC oxidized glutathione was
      negatively correlated with dietary vitamin E. GSH redox status was expressed as
      the GSH-to-total GSH ratio; the ratio was also positively correlated with dietary
      vitamin E and was significantly greater in rats fed 1,500 ppm vitamin E than in
      rats fed no vitamin E (p < 0.05). For antioxidant enzymes, superoxide dismutase
      activity in hepatic cytosolic fraction was significantly greater in rats fed
      1,500 ppm vitamin E than in rats fed 100 ppm vitamin E. Hepatic GSH reductase
      activity was significantly greater in rats fed 100 ppm vitamin E than in rats fed
      no vitamin E (p < 0.05). Dietary vitamin E had no effect on plasma vitamin C and
      protein thiol levels. In the systems studied, results indicated that dietary
      vitamin E selectively influences plasma vitamin E level, RBC GSH status, and
      hepatic cytosolic superoxide dismutase and GSH reductase activities.

PMID- 9919619
TI  - Vitamin E prevents induction of carbonyl group formation in microsomal protein by
      dehydroepiandrosterone.
AB  - The effect of dehydroepiandrosterone (DHEA), a free radical- and lipid peroxide
      inducing agent, and of vitamin E (alpha-tocopherol), a free radical chain
      terminator, on protein carbonyl group formation was investigated in rat liver
      microsomes. Administration of alpha-tocopherol at 25-50 mg/kg diet for seven days
      resulted in high Fe(2+)-NADPH-ADP-dependent production of protein carbonyl groups
      in liver microsomal protein isolated from otherwise untreated rats. However,
      alpha-tocopherol administered at > 100 mg/kg diet caused a decrease in the
      production of protein carbonyl groups. In animals simultaneously receiving alpha
      tocopherol at 50 mg/kg diet and DHEA at 500 mg/kg diet, no additional stimulatory
      effect of the steroid on microsomal protein carbonyl group production was
      observed. Protein carbonyl group production was significantly enhanced by DHEA in
      rats given a diet containing 400 mg alpha-tocopherol/kg diet. Microsomes isolated
      from rats fed 1,000 mg alpha-tocopherol/kg diet with DHEA (500 mg/kg diet) and
      without DHEA produced small but similar amounts of protein carbonyl groups. These
      results provide evidence that vitamin E is an important protective agent against
      DHEA-mediated oxidative damage of intracellular components, including proteins.

PMID- 9919621
TI  - Nicotinic acid supplementation: effects on niacin status, cytogenetic damage, and
      poly(ADP-ribosylation) in lymphocytes of smokers.
AB  - As a substrate for poly(ADP-ribose) polymerase (PARP; EC, 2.4.2.30), an enzyme
      that is activated by DNA strand breaks and is thought to facilitate efficient DNA
      repair, NAD+ and its precursor nicotinic acid (niacin) are involved in the
      cellular defense against DNA damage by genotoxic compounds. In this study, the
      effect of nicotinic acid supplementation on cytogenetic damage and poly(ADP
      ribosylation) was evaluated in a human population that is continuously exposed to
      genotoxic agents, e.g., smokers. By use of a placebo-controlled intervention
      design, 21 healthy smokers received supplementary nicotinic acid at 0-100 mg/day
      for 14 weeks. An increased niacin status, as assessed from blood nicotinamide
      concentrations and lymphocyte NAD+ concentrations, was observed in groups
      supplemented with 50 and 100 mg/day. This effect was most pronounced in subjects
      with lower initial NAD+ levels. An increased niacin status did not result in
      decreased hypoxanthine guanine phosphoribosyltransferase variant frequencies and
      micronuclei induction in peripheral blood lymphocytes (PBLs). Sister chromatid
      exchanges in PBLs, however, were increased after supplementation with nicotinic
      acid. This increase was positively associated with the daily dose of nicotinic
      acid. No effects of nicotinic acid supplementation were found for ex vivo (+/-)-7
      beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
      induced poly(ADP-ribosylation), although the small number of samples that could
      be analyzed (n = 12) does not allow firm conclusions. Because no evidence was
      found for a decrease in cigarette smoke-induced cytogenetic damage in PBLs of
      smokers after nicotinic acid supplementation of up to 100 mg/day, it is concluded
      that supplemental niacin does not contribute to a reduced genetic risk in healthy
      smokers.

PMID- 9919622
TI  - Expressed emotion and differentiation of self in the relatives of stable
      schizophrenia outpatients.
AB  - This study examined "trait" variables associated with high and low levels of
      expressed emotion in the parents of long-term stable schizophrenia outpatients.
      Self-descriptions collected from patients, their parents, and control
      participants matched to the parents were rated for levels of differentiation and
      integration, substantiality, relatedness, and self-criticism using established
      methods. The parents as a group did not differ from controls on any of the self
      description variables. When parents were classified based on their expressed
      emotion status, those with low expressed emotion showed higher levels of
      differentiation and integration than those with high expressed emotion. Low
      expressed emotion parents were also lower on self-criticism. There was no
      difference between expressed emotion groups on substantiality or relatedness.
      These findings support the idea that high expressed emotion in parents of long
      term stable outpatients may be a manifestation in part of relatively low levels
      of differentiation and integration of self in the parents. Furthermore, though
      patients as a group scored lower than parents on differentiation and integration
      and substantiality, patients' ratings on these two variables also correlated with
      those of their parents, suggesting that these variables are to some extent
      familially determined.

PMID- 9919620
TI  - Dietary fiber differentially alters cellular fatty acid-binding protein
      expression in exfoliated colonocytes during tumor development.
AB  - We investigated the utility of noninvasive technology utilizing feces containing
      exfoliated colonocytes to determine whether changes in fecal fatty acid-binding
      proteins have predictive value in monitoring the neoplastic process. Ninety male
      Sprague-Dawley rats were randomly divided into four groups in a 2 x 2 factorial
      design, with two dietary fiber sources (wheat bran or oat bran) and two treatment
      groups (injection with a carcinogen, azoxymethane, or saline). Fresh fecal
      samples were collected at Week 16 postinjection, and tumor frequency was
      determined at Week 36 of the study. Semiquantitative "mimic" reverse
      transcriptase polymerase chain reaction was used to quantitate the expression of
      liver fatty acid-binding protein (L-FABP), intestinal fatty acid-binding protein
      (i-FABP), and acyl CoA-binding protein (ACBP) mRNA in fecal samples to establish
      their prognostic value. Rats fed wheat bran diets had a lower incidence of tumors
      (p < 0.05). There was no effect of carcinogen injection or tumor incidence on the
      expression of L-FABP, i-FABP, or ACBP mRNA, L-FABP and i-FABP mRNA expression
      were significantly higher (p < 0.05) in feces from animals fed a wheat bran diet
      than in feces from animals fed an oat bran diet. In contrast, the expression of
      ACBP mRNA was significantly lower (p < 0.05) in animals fed a wheat bran diet
      than in animals fed an oat bran diet. Wheat bran also increased (p < 0.05) the
      total excretion of L-FABP, i-FABP, and ACBP over a 48-hour period. These data
      suggest that exfoliated colonocyte fatty acid-binding protein mRNA status may
      provide insight into the mechanisms by which diet influences colonic physiology.

PMID- 9919623
TI  - Applying an empty-chair monologue paradigm to examine unresolved grief.
AB  - In this study the Gestalt empty-chair technique was applied in a research context
      to assess unresolved grief and its relation to later adjustment. Bereaved
      individuals who experienced the death of a spouse on average 6 months ago
      participated in an empty-chair monologue task in which they were instructed to
      speak to their deceased spouse, imagining that they had one last opportunity to
      do so. They completed a questionnaire at the end of their monologue speech
      assessing their affective experience during the monologue. It contained items
      associated with unresolved grief (e.g., anger, guilt, helplessness,
      nonacceptance). Near the time of the monologue session, bereaved participants
      also completed the Beck Depression Inventory (BDI) (Beck and Steer 1987) and the
      Impact of Event Scale (IES) (Horowitz, Wilner, and Alvarez 1979). At 14 months
      postloss, bereaved participants again were administered the BDI and IES. As
      hypothesized, the extent of unresolved grief as assessed by the monologue
      questionnaire at 6 months postloss was predictive of 14-month postloss symptoms,
      even when statistically controlling for 6-month postloss symptoms in hierarchical
      regression analyses.

PMID- 9919624
TI  - Clinical trials and tribulations: implementation processes in schizophrenia
      research outcome.
AB  - This article focuses on an area in clinical drug trials for new antipsychotic
      medications for the treatment of schizophrenia which has not received sufficient
      attention in the literature: the day-to-day implementation tasks performed by
      research staff which have potential effects on study results. Implementation
      tasks are viewed as dynamic processes involving interactions among research and
      nonresearch staff, patients, families, and pharmaceutical company staff. Research
      related demands and possible sources of stress for all participants in the
      process, such as recruiting and maintaining patients in studies, are discussed.
      Suggestions are offered for increasing the ease of participation. Further
      investigation is called for in several areas including variability in the
      effectiveness of research teams and in the rarely discussed interactions between
      site staff and pharmaceutical company personnel, as they may affect research
      outcomes. It is posited that increased knowledge about implementation processes
      in schizophrenia drug development is needed to more fully understand study
      results and to enhance patients' and their families' willingness to participate.

PMID- 9919625
TI  - Mental health providers confronting organizational change: process, problems, and
      strategies.
AB  - Under the influence of managed care and diminished funding, the mental health
      field is undergoing a major transformation. Existing mental health programs,
      departments, and agencies are downsizing and restructuring to develop new types
      of service delivery systems. Organizations must change to survive; yet necessary
      and adaptive change may be resisted in numerous ways by providers whose reactions
      and behaviors may reduce the viability of their own programs and agencies. This
      paper explores various characteristics and reactions of mental health care
      professionals as they face great stress, professional devaluation, and necessary
      organizational change and restructuring. Adaptive and maladaptive patterns in
      response to potential organizational change are explored. The role of the leader
      in guiding and implementing programmatic changes and in dealing with denial and
      resistance is highlighted. Strategies to enhance the prospects for adaptive
      organizational change are offered.

PMID- 9919626
TI  - Short-term treatment of a Central American torture survivor.
AB  - The short-term treatment of a Honduran torture survivor is recounted. Torture-
      the "counter-therapy of the State" (Ritterman 1987, p. 43)--involves intentional
      physical and psychological destruction of human beings. The socio-political
      context in which the traumatic events occurred is described, as are the
      theoretical and ethical assumptions underlying the work. Treatment of victims of
      organized violence is a formidable challenge. Obstacles and advantages of short
      term psychotherapy and use of the therapist's emotional reactions to understand
      survivors' experiences are emphasized.

PMID- 9919627
TI  - Commentary on Munczek's "short-term treatment of a Central American torture
      survivor.".

PMID- 9919628
TI  - Families, culture, and mental illness: constructing new realities.
AB  - In Modern Western cultures, conceptual models of mental illness are interwoven
      with value systems of individualism, agency, internal locus of control, and fear
      of dependency. These values have translated into psychological theory and
      practice, affected families' relationships with the professional, legal, and
      consumer communities and have often exacerbated family burden. Culturally
      patterned attributions of individual accountability also affect family-patient
      interactions and may have an effect on relapse and prognosis. The family and
      consumer movements are discussed in terms of their orientations, services, social
      impact, and influence on epistemology, particularly with reference to the
      different effects of protective paternalism and individualistic autonomy.
      Questions are raised regarding cultural values and differential prognoses in
      modern and developing countries and whether the process of recovery may be shaped
      by different cultural introjects. It is suggested that the era of family and
      consumer empowerment may be heuristic in discovering parameters of mental illness
      and potential for recovery, and ideas are offered for future cross-cultural
      research.

PMID- 9919630
TI  - Covert contraceptive use: prevalence, motivations, and consequences.
AB  - This article examines women's covert use of contraceptives, that is, their use of
      a method without their husbands' knowledge. Three questions are addressed: (1)
      How is covert use measured? (2) How prevalent is it? and (3) What are the factors
      underlying covert use? Existing studies are used together with survey and
      qualitative data collected in 1997 in an urban setting in Zambia from married
      women and their husbands. Women's covert use of contraceptives is estimated to
      account for 6 to 20 percent of all current contraceptive use, and it is more
      widespread when contraceptive prevalence is low. The multivariate analysis
      indicates that difficult spousal communication about contraception is the
      strongest determinant of covert use. Husbands' disapproval of contraception works
      through spousal communication rather than as a direct influence on covert use.
      Husbands' pronatalism had no significant effect. The article concludes with
      implications of covert use for reproductive health and family planning programs,
      especially women's (and men's) needs for confidential services.

PMID- 9919629
TI  - Dead mothers and injured wives: the social context of maternal morbidity and
      mortality among the Hausa of northern Nigeria.
AB  - Northern Nigeria has a maternal mortality ratio greater than 1,000 maternal
      deaths per 100,000 live births. Serious maternal morbidity (for example, vesico
      vaginal fistula) is also common. Among the most important factors contributing to
      this tragic situation are: an Islamic culture that undervalues women; a perceived
      social need for women's reproductive capacities to be under strict male control;
      the practice of purdah (wife seclusion), which restricts women's access to
      medical care; almost universal female illiteracy; marriage at an early age and
      pregnancy often occurring before maternal pelvic growth is complete; a high rate
      of obstructed labor; directly harmful traditional medical beliefs and practices;
      inadequate facilities to deal with obstetric emergencies; a deteriorating
      economy; and a political culture marked by rampant corruption and inefficiency.
      The convergence of all of these factors has resulted in one of the worst records
      of female reproductive health existing anywhere in the world.

PMID- 9919631
TI  - Looking locally at China's one-child policy.
AB  - Of all the reforms and policies set in motion in the early 1980s in China, the
      one-child policy has been called the most far-reaching in its implications for
      China's population and economic development. Almost two decades later, little is
      known about what the policy looks like across local neighborhoods and villages.
      To sketch a more general picture of the one-child policy, this article presents
      panel data from three waves of the China Health and Nutrition Survey (1989, 1991,
      and 1993) collected in 167 communities in eight provinces. Local policy,
      including policy strength and policy incentives and disincentives, is detailed
      separately for urban and rural areas. These data confirm that no single one-child
      policy exists; policy varied considerably from place to place and within
      individual communities during the 1989-93 period.

PMID- 9919632
TI  - Husbands' reproductive health knowledge, attitudes, and behavior in Uttar
      Pradesh, India.
AB  - To enhance the reproductive health status of couples in developing countries, the
      knowledge, attitudes, and behavior of both women and men must be investigated,
      especially where women depend on men for the decision to seek care. This study
      analyzes data from a survey of 6,727 husbands from five districts in the northern
      state of Uttar Pradesh, India. Data are presented on men's knowledge of women's
      health and on their own sexual behavior outside the context of marriage, on their
      perceptions of sexual morbidity and their attempts at treatment for specific
      conditions, and on their opinions concerning the social role of wives. Findings
      indicate that men know little about maternal morbidity or sexual morbidity
      conditions. Few husbands reported that they had had sexual experience outside of
      marriage and the majority of these few said they had had such a relationship with
      more than one partner. Of men who said they had had reproductive morbidity
      symptoms, many said they had not sought treatment. Men's views concerning the
      role of wives indicate a low level of women's autonomy in this region of India.
      Results indicate a pressing need for reproductive health education that targets
      both women and men in Uttar Pradesh.

PMID- 9919633
TI  - Husbands' involvement in abortion in Vietnam.
AB  - This study analyzes the involvement of men in abortion in Vietnam, where induced
      abortion is legal and abortion rates are among the highest in the world. Twenty
      men were interviewed in 1996 about the role they played in their wives' abortions
      and about their feelings and ethical views concerning the procedure. The results
      showed that both husbands and wives considered the husband to be the main
      decisionmaker regarding family size, which included the decision to have an
      abortion, but that, in fact, some women had undergone an abortion without
      consulting their husbands in advance. Parents and in-laws were usually not
      consulted; the couples thought they might object to the decision on moral
      grounds. Respondents' ethical perspectives on abortion are discussed. When faced
      with an unwanted pregnancy, the husbands adopted an ethics of care and
      responsibility toward family and children, although some felt that abortion was
      immoral. The study highlights the importance of understanding husbands'
      perspectives on their responsibilities and rights in reproductive decisionmaking
      and their ethical and other concerns related to abortion.

PMID- 9919634
TI  - The validity of verbal autopsies for assessing the causes of institutional
      maternal death.
AB  - This report presents data from a study carried out in three African countries to
      assess the validity of verbal autopsies--based on information about symptoms and
      signs observed antemortem by relatives or associates of deceased individuals--for
      determining the causes of institutional maternal death. The validity of the
      verbal autopsy was assessed for each cause of death; and for groups of "direct"
      and "indirect" maternal causes, by comparing the verbal autopsy diagnoses with
      the reference diagnoses and calculating their sensitivity, specificity, and
      positive predictive value. Verbal autopsies were found to be highly specific (98
      percent specificity for all causes of maternal death) but not very sensitive (<
      or = 60 percent sensitivity for all causes except ante/postpartum hemorrhage).
      Verbal autopsy estimates of cause-specific mortality were comparable to expected
      values for most of the causes. The study shows that certain direct causes of
      hospital-based maternal mortality can be determined by means of verbal autopsies
      with a reasonable level of confidence.

PMID- 9919635
TI  - Dominican Republic 1996: results from the demographic and health survey.

PMID- 9919636
TI  - Zambia 1996: results from the demographic and health survey.

PMID- 9919637
TI  - Maternal death and birth spacing.

PMID- 9919638
TI  - Measuring performance in child welfare: secondary effects of success.
AB  - The Adoption and Safe Families Act of 1997 mandates the development of a system
      to rate the performance of state child welfare programs. The resulting system,
      built on broader efforts to measure outcomes for children and families who
      receive support and services from the child welfare system, will inform
      perspectives on family foster care in the next century. Drawing on findings from
      evaluations of recent reform initiatives in Alabama, North Carolina, and Ohio,
      this article suggests that performance measurement systems must be adaptable to
      changing circumstances, particularly when improvements in one area can affect
      standards and expectations in others.

PMID- 9919639
TI  - Satisfaction of children in out-of-home care.
AB  - A randomly selected sample of 1,100 children in out-of-home care in Illinois from
      1993 to 1996 were interviewed in person regarding their satisfaction with the
      homes in which they lived and with their caregivers. They were also asked whether
      they felt loved and safe, and rated the quality of their lives before and after
      placement into care. The children rated their satisfaction with their living
      arrangements and with their caregivers as high, especially those who had lived in
      family foster care.

PMID- 9919640
TI  - Concurrent planning: benefits and pitfalls.
AB  - Concurrent planning-working with families toward reunification while developing
      alternative permanency plans--was designed to fit an out-of-home care population
      much like that projected for the year 2000 and beyond: very young, chronically
      neglected children from multiproblem families. As large-scale programs begin to
      develop nationally, those implementing concurrent planning must be aware of the
      pitfalls that can undercut its effectiveness, while keeping in mind the benefits
      it can bring by reducing the trauma experienced by children in placement.

PMID- 9919641
TI  - Shared family care: providing services to parents and children placed together in
      out-of-home care.
AB  - Shared family care involves the planned provision of out-of-home care to parents
      and their children so that the parent and the host caregivers simultaneously
      shared the care of the children and work toward independent in-home care by the
      parent. This article describes several innovative types of shared family care
      arrangements that demonstrate promise in the protection of children and the
      promotion of family well-being. Emphasis is placed on the shared family foster
      care model, including its key elements, funding, and evaluation.

PMID- 9919642
TI  - Starting young: improving the health and developmental outcomes of infants and
      toddlers in the child welfare system.
AB  - The number of infants and toddlers entering out-of-home care has increased
      dramatically in the past few years, yet few published reports examine their
      needs. This article describes a collaborative, multidisciplinary developmental
      follow-up program for infants and toddlers that builds on the community-based
      family support model described in the Family to Family Foster Care Reform
      Initiative. The children's health and developmental status, as well as the
      program's effectiveness, are highlighted.

PMID- 9919644
TI  - The impact of drug-exposed children on family foster care.
AB  - To determine whether infants exposed to drugs during gestation present special
      challenges in family foster care, data on 204 infants were reviewed.
      Developmental functioning, health and caregiving needs, visits by biological
      parents, and case dispositions were compared across drug-exposure groups. Infants
      with verified drug exposure presented with significantly more health and
      caregiving needs, had fewer biological parent visits, and were more frequently
      placed with relatives after family foster care. Findings are discussed in terms
      of their impact on family foster care in the next century.

PMID- 9919643
TI  - Delivering health and mental health care services to children in family foster
      care after welfare and health care reform.
AB  - As the 20th century draws to a close, fundamental changes in the organization,
      financing, and delivery of health care and welfare services, principally directed
      at poor families, are likely to result in an increased number of children
      entering out-of-home care. These children typically have significant physical,
      mental health, and developmental problems. Whether the quality of health care
      services they receive will improve as a result of health care reform efforts and
      new approaches to service delivery remains to be seen. This article addresses
      some of the major changes wrought by welfare and health care reform and describes
      the essential features of a health care system that can meet the special needs of
      children in care.

PMID- 9919645
TI  - Evaluation of a training program for foster parents of infants with prenatal
      substance effects.
AB  - The lack of prepared and available foster parents for children with prenatal
      substance effects is of increasing concern to the child welfare field. The
      research study reported here evaluated a multimodal inservice training program
      designed to enhance the competency of foster parents caring for infants with
      prenatal substance effects, and to promote an intent to foster such infants.
      Findings suggest that future foster parent training efforts in this area should
      focus on knowledge and skill attainment.

PMID- 9919646
TI  - Purification and characterization of a hydroperoxidase from the cyanobacterium
      Synechocystis PCC 6803: identification of its gene by peptide mass mapping using
      matrix assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - A cytosolic catalase-peroxidase from the cyanobacterium Synechocystis PCC 6803
      was purified to homogeneity by a six-step purification procedure. It is a
      homodimeric enzyme with a subunit molecular mass of 85 kDa. The isoelectric point
      of the protein is at pH 5.5; Michaelis constant, turnover number, and catalytic
      efficiency of the catalase activity for H2O2 were measured to be 4.8 mM, 3450 s
      1, and 7.2 x 10(5) M-1 s-1, respectively. Preparation and spectroscopy of the
      pyridine ferrohemochrome identified an iron protoporphyrin IX as the prosthetic
      group. The enzyme was shown to exhibit both catalase and peroxidase activities,
      both of which were inhibited by cyanide, leading to a high-spin to low-spin
      transition of the heme iron center as detected by a shift of the Soret peak from
      405 to 421 nm. The catalase-specific inhibitor 3-amino-1,2,4-triazole proved
      ineffective. o-Dianisidine, pyrogallol and guaiacol functioned as a peroxidatic
      substrate, but no reaction was detected with NADH, NADPH, glutathione, and
      ascorbate. Peptide mass mapping using matrix assisted laser desorption ionization
      time-of-flight mass spectrometry showed the identity between the purified protein
      and a putative katG gene derived from the genome of Synechocystis PCC 6803. A
      comparison of amino acid sequences of the catalase-peroxidase from Synechocystis
      PCC 6803 and those from other bacteria showed a high homology around the assumed
      distal and proximal histidine residues, suggesting a highly conserved histidine
      as the fifth ligand of the heme iron.

PMID- 9919647
TI  - Variable expression of glutathione S-transferase isoenzymes in the fungus, Mucor
      circinelloides.
AB  - Mucor circinelloides (previously M. javanicus) variably expresses two isoenzymes
      of glutathione S-transferases. Glutathione S-transferases 1 and 2 were purified
      by affinity chromatography and found to be dimers with subunit M(r) values of
      25.5 and 28. While glutathione S-transferase 1 immunoblotted with rat glutathione
      S-transferase T 5-5, N-terminal sequencing indicated that this enzyme was
      distinct from recently characterised bacterial and fungal glutathione S
      transferases and did not readily fit into any one class. It showed some
      similarity to several classes including insect class II and plant type III. M.
      circinelloides glutathione S-transferase 2 did not immunoblot and yielded no N
      terminal sequence.

PMID- 9919648
TI  - Effect of nitrogen oxides on expression of the nir and nor genes for
      denitrification in Pseudomonas aeruginosa.
AB  - The activity of the promoters involved in transcription of the genes (nirS, nirQ
      and norC) required for anaerobic reduction of nitrite and nitric oxide was
      investigated in NIR- and NOR-deficient mutants of Pseudomonas aeruginosa. The
      transcriptional activity of these three promoters was induced by nitrite in a
      wild-type strain and the activity was low in an nirS mutant. In norCBD and nirQOP
      mutants, which were expected to accumulate nitric oxide because of a lack of
      nitric oxide reductase activity, the norC and nirQ promoters showed significantly
      enhanced activity in promoting transcription relative to the parental strain,
      even at low nitrite concentrations. These results suggest that the nirQ and norC
      promoters are regulated by the concentration of endogenous nitric oxide rather
      than that of nitrite.

PMID- 9919649
TI  - Strain typing among enterococci isolated from home-made Pecorino Sardo cheese.
AB  - Three molecular techniques (RAPD-polymerase chain reaction analysis, plasmid
      profile and pulsed-field gel electrophoresis) were used for a preliminary
      approach to type, at strain level, enterococci isolated from a 24-h-old home-made
      Pecorino Sardo (protected designation of origin) cheese. A high genetic
      polymorphism was found. Clusters obtained by the RAPD technique and plasmid
      profile analysis contained different strains. Pulsed-field gel electrophoresis
      proved to be an efficient and highly reproducible typing method. In addition, by
      combining the results from plasmid profile analysis and pulsed-field gel
      electrophoresis, it was possible to identify closely related strains probably
      belonging to the same clonal lineage.

PMID- 9919650
TI  - The alcohol dehydrogenase gene: distribution among Sulfolobales and regulation in
      Sulfolobus solfataricus.
AB  - The distribution of the alcohol dehydrogenase gene (adh) among different Archaea
      was investigated by Southern blot analysis revealing the potentiality of the adh
      gene as a specific marker for the genus Sulfolobus. Moreover, the in vivo
      expression of the adh gene from a new isolate of Sulfolobus solfataricus, G
      theta, was studied to investigate gene regulation in Archaea. Primer extension
      analysis allowed the identification of a single initiation site and the TATA box
      element. Comparison of the G theta adh promoter with the corresponding Ssadh (adh
      from S. solfataricus) and RC3adh (adh from Sulfolobus RC3) also revealed the
      presence of two putative regulatory inverted repeats at the 5' of the TATA
      element. Northern blot analysis and enzymatic assays demonstrated that the
      transcription and expression of the G theta adh gene is regulated by different
      carbon and energy sources or by the natural substrate of the ADH enzyme.

PMID- 9919651
TI  - Expression and secretion of Bacillus polymyxa neopullulanase in Saccharomyces
      cerevisiae.
AB  - We have isolated the gene encoding the neopullulanase enzyme from Bacillus
      polymyxa CECT 155. It consists of an open reading frame of 1545 bp that could
      code for a protein of 515 amino acids. This open reading frame was expressed in
      Bacillus subtilis and the corresponding transformants produced extracellular
      neopullulanase. The neopullulanase gene was also expressed in Saccharomyces
      cerevisiae placing it under the control of the yeast actin gene (ACT1) promoter.
      Clones containing the intact neopullulanase gene, including its own bacterial
      signal sequence, gave rise to the synthesis of active, but intracellular, enzyme
      by S. cerevisiae transformants. When sequences specifying the signal sequence and
      leader region of the yeast mating pheromone alpha-factor (MF alpha 1) were fused
      upstream of the gene encoding the neopullulanase enzyme, the enzyme was secreted
      by S. cerevisiae. The secreted protein presented the same biochemical properties
      and the same apparent molecular mass as the Bacillus polymyxa original enzyme.
      The predicted amino acid sequence of the neopullulanase protein contained
      sequence motifs conserved among amylolytic enzymes. Northern blot analysis
      indicated that the transcription of the neopullulanase gene in B. polymyxa was
      induced by the presence of the substrate, pullulan, in the culture, and was
      repressed by glucose.

PMID- 9919652
TI  - Chitin synthase genes in the arbuscular mycorrhizal fungus Glomus versiforme:
      full sequence of a gene encoding a class IV chitin synthase.
AB  - Chitin synthase genes of the arbuscular mycorrhizal fungus Glomus versiforme were
      sought in an investigation of the molecular basis of fungal growth. Three DNA
      fragments (Gvchs1, Gvchs2 and Gvchs3) corresponding to the conserved regions of
      distinct chitin synthase (chs) genes were amplified by means of the polymerase
      chain reaction (PCR) with two sets of degenerate primers. Gvchs1 and Gvchs2
      encode two class I chitin synthases, whereas Gvchs3 encodes a class IV chitin
      synthase. A genomic library was used to obtain the Gvchs3 complete gene (1194
      amino acids), which shows a very close similarity to the class IV chitin synthase
      from Neurospora crassa.

PMID- 9919653
TI  - Co-expression of polyhydroxyalkanoate synthase and (R)-enoyl-CoA hydratase genes
      of Aeromonas caviae establishes copolyester biosynthesis pathway in Escherichia
      coli.
AB  - Polyhydroxyalkanoate biosynthesis genes of Aeromonas caviae were expressed in
      Escherichia coli LS5218 (fadR atoC(Con)), and the polyhydroxyalkanoate-producing
      ability of the recombinants was investigated. A LS5218 strain harboring only
      phaCAc (polyhydroxyalkanoate synthase gene) did not accumulate any
      polyhydroxyalkanoate from dodecanoate in spite of the existence of translated
      polyhydroxyalkanoate synthase protein, whereas co-expression phaCAc and phaJAc
      ((R)-specific enoyl-CoA hydratase gene) resulted in the accumulation of P(3
      hydroxybutyrate-co-3-hydroxyhexanoate) copolymer up to 7-11 wt% of dry cell
      weight from octanoate and dodecanoate. These results indicated that both phaCAc
      and phaJAc are essential for E. coli LS5218 to establish the polyhydroxyalkanoate
      biosynthesis pathway from alkanoic acids. The copolyester content in the strain
      expressing both the genes under the lac promoter control reached to 38 wt% from
      dodecanoate. Enzyme assays suggest that efficient monomer formation via beta
      oxidation by a high level expression of phaJAc was important to achieve a high
      polyhydroxyalkanoate content in the recombinant E. coli.

PMID- 9919654
TI  - Transcriptional regulation of Nostoc uptake hydrogenase.
AB  - Filamentous, heterocystous cyanobacteria may contain both an uptake hydrogenase
      (encoded by hupSL) and a bidirectional enzyme (encoded by hoxFUYH). The present
      study identifies three strains (Anabaena variabilis, Nostoc muscorum and Nostoc
      sp. strain PCC 73102) with a contiguous hupL in both vegetative cells and
      heterocysts. The two Nostoc strains differ in either containing a bidirectional
      enzyme (N. muscorum) or lacking this enzyme (N. PCC 73102). Transcriptional
      studies, using reverse transcriptase-polymerase chain reaction, demonstrated an
      induction of a hupL transcript approximately 24 h after a shift from non-nitrogen
      fixing to nitrogen-fixing conditions (in parallel with the induction of an in
      vivo light-dependent H2-uptake activity) in N. muscorum. However, the level of
      hoxH transcripts did not change significantly during the induction of the H2
      uptake activity.

PMID- 9919655
TI  - Ultrastructural characterization of Anaerobiospirillum succiniciproducens and its
      differentiation from Campylobacter species.
AB  - The anaerobic spiral-shaped bacterium Anaerobiospirillum succiniciproducens was
      isolated from the blood of an AIDS patient for the first time in Europe. Electron
      microscopical methods, especially negative staining, allowed rapid morphological
      classification and differentiation from Campylobacter species. While A.
      succiniciproducens revealed lophotriche flagellation all the investigated
      Campylobacter species showed monotriche flagellation. The cell diameter of A.
      succiniciproducens was at least double that of the investigated Campylobacter
      species. Other ultrastructural features, such as a ring-like structure underneath
      the flagellar area and fibrils arranged parallel along the axis, were also
      specific to A. succiniciproducens.

PMID- 9919656
TI  - Weak organic acid treatment causes a trehalose accumulation in low-pH cultures of
      Saccharomyces cerevisiae, not displayed by the more preservative-resistant
      Zygosaccharomyces bailii.
AB  - Weak organic acid food preservatives exert pronounced culture pH-dependent
      effects on both the heat-shock response and the thermotolerance of Saccharomyces
      cerevisiae. In low-pH cultures, they inhibit this stress response and cause
      strong induction of respiratory-deficient petites amongst the survivors of lethal
      heat treatment. In higher pH cultures, 25 degrees C sorbic acid treatment causes
      a strong induction of thermotolerance without inducing the heat-shock response.
      In this study we show that trehalose, a major stress protectant, accumulates
      rapidly in S. cerevisiae exposed to sorbate at low pH. In pH 3.5 cultures, a 25
      degrees C sorbate treatment is as effective as a 39 degrees C heat shock in
      inducing trehalose. This weak-acid-induced trehalose accumulation is enhanced in
      the pfk1 S. cerevisiae mutant, indicating that it arises through inhibition of
      glycolysis at the phosphofructokinase step. The more preservative-resistant food
      spoilage yeast Zygosaccharomyces bailii differs from S. cerevisiae in that: (1)
      its basal thermotolerance is not strongly affected by culture pH; (2) it does not
      display trehalose accumulation in response to 25 degrees C sorbate treatment at
      low pH; and (3) there is no induction of respiratory-deficient petites during
      lethal heating with sorbate. This probably reflects Z. bailii being both petite
      negative and better equipped for maintenance of homeostasis during weak-acid, pH
      or high-temperature stress.

PMID- 9919657
TI  - Genetic analysis of the cap5 locus of Staphylococcus aureus.
AB  - Staphylococcus aureus expresses at least eight distinct serotypes of capsular
      polysaccharide (CP). Gene clusters involved in the expression of serotypes 1, 5
      and 8 have been cloned and sequenced. In this report we describe the isolation
      and analysis of serotype 5 capsular polysaccharide-defective mutants. A naturally
      occurring cap mutation in the laboratory strains 8325-4 and RN4220 was mapped to
      the cap5E gene by genetic complementation. The cap5H-K genes were shown to be
      responsible for CP5 serotype specificity by transduction and complementation.

PMID- 9919658
TI  - Active alpha-glucoside transport in Saccharomyces cerevisiae.
AB  - The AGT1 permease is a alpha-glucoside-H+ symporter responsible for the active
      transport of maltose, trehalose, maltotriose, alpha-methylglucoside, melezitose
      and sucrose. In wild-type as well as in MAL constitutive strains, alpha
      methylglucoside seemed to be the best inducer of transport activity, while
      trehalose had no inducing effect. Based on the initial rates of transport it
      seems that the sugar preferentially transported by this permease is trehalose,
      followed by sucrose.

PMID- 9919659
TI  - Characterisation of rhizobia from African acacias and other tropical woody
      legumes using Biolog and partial 16S rRNA sequencing.
AB  - A Biolog (sole carbon source utilisation) user database of tropical and
      temperature rhizobial strains was created and used in conjunction with the
      partial 16S rRNA sequencing method to characterise 12 rhizobial isolates from
      African acacias and other tropical woody legumes. There was close agreement
      between the two methods but also some significant discrepancies. A high degree of
      diversity was shown in the relatively small sample of isolates, with 4 out of 5
      of the currently proposed rhizobial genera represented. This is the first time
      Biolog has shown congruence with genotypic fingerprinting using a wide selection
      of rhizobial reference and test strains.

PMID- 9919660
TI  - Functional characterisation of the chaperones DnaK, DnaJ, and GrpE from
      Clostridium acetobutylicum.
AB  - The DnaK chaperone system is involved in various cellular processes such as the
      control of the folded and oligomeric state of proteins under stress and non
      stress conditions. In this study we functionally characterised the homologues of
      the DnaK system from Clostridium acetobutylicum DnaK, DnaJ, GrpE and OrfA were
      heterologously synthesised in Escherichia coli and affinity purified via a His
      tag. By optimising the stoichiometry, we were able to refold guanidinium
      hydrochloride-denatured firefly luciferase in vitro with 22% of the yield
      obtained with the E. coli DnaK system. In addition, C. acetobutylicum DnaJ could
      stimulate the E. coli DnaK ATPase by a factor of 55. Furthermore, the DnaK system
      from C. acetobutylicum was able to prevent the aggregation of OrfA from C.
      acetobutylicum, which is similar to the repressor HrcA of CIRCE-regulated heat
      shock genes in Bacillus subtilis.

PMID- 9919661
TI  - Isolation of csm1 encoding a class V chitin synthase with a myosin motor-like
      domain from the rice blast fungus, Pyricularia oryzae.
AB  - A gene encoding a chitin synthase with a myosin motor-like domain (csm1) was
      isolated from Pyricularia oryzae using a PCR fragment amplified from a fungal
      chitin synthase conserved region. The deduced amino acid sequence of csm1 is
      homologous to that of CsmA of Aspergillus nidulans (65% identity). The putative
      gene product of csm1 is consisted of the myosin motor-like domain and a chitin
      synthase domain as in A. nidulans csmA. The chitin synthase domain of its C
      terminus was also homologous to Aspergillus fumigatus ChsE (61.4% identity) and
      Ustilago maydis Chs6 (48.6% identity) that encode class V chitin synthases.
      Northern analysis demonstrated that the csm1 was expressed throughout the
      mycelial growth of P. oryzae. This is the first report on the isolation of the
      gene encoding a class V chitin synthase with the myosin motor-like domain from P.
      oryzae.

PMID- 9919662
TI  - The rpoS mutant allele of Salmonella typhi Ty2 is identical to that of the live
      typhoid vaccine Ty21a.
AB  - Salmonella requires its alternative sigma factor sigma S (RpoS) for virulence in
      mice. rpoS mutants can be frequently isolated from highly passaged Salmonella
      laboratory strains. In particular, the live typhoid oral vaccine Salmonella typhi
      Ty21a and its parental strain Ty2, a 'wild-type' strain widely used for vaccine
      development, are rpoS mutants. Here, we show that the nucleotide sequence of the
      rpoS mutant allele of Ty2 is identical to that of the rpoS mutant allele of
      Ty21a. This demonstrates that the rpoS mutation arose in Ty2 before the isolation
      of Ty21a in 1975, an observation that may have implications for vaccine research.

PMID- 9919663
TI  - The ferripyoverdine receptor FpvA of Pseudomonas aeruginosa PAO1 recognizes the
      ferripyoverdines of P. aeruginosa PAO1 and P. fluorescens ATCC 13525.
AB  - FpvA, the ferripyoverdine outer membrane receptor of Pseudomonas aeruginosa ATCC
      15692 (PAO1 strain), is not specific to the pyoverdine produced by PAO1, but is
      also able to recognize the structurally different (ferri)pyoverdine of P.
      fluorescens ATCC 13525. The specificity of FpvA was assessed by iron uptake
      competitions using the wild-type strains P. aeruginosa ATCC 15692 and P.
      fluorescens ATCC 13525 and their respective ferripyoverdines, and by fpvA gene
      complementation of a FpvA-deficient mutant of P. aeruginosa ATCC 15692. The
      receptor mutant was able to utilize none of the two pyoverdines, while the same
      but fpvA-complemented mutant recovered simultaneously the ability to incorporate
      iron thanks to each of the two siderophores. The broad specificity of recognition
      of FpvA is viewed as an advantage for the strain in iron competition. Moreover,
      it allows an interesting approach for the understanding of the recognition
      mechanism between a (ferri)pyoverdine and its cognate outer membrane receptor.

PMID- 9919664
TI  - Presence of erm gene classes in gram-positive bacteria of animal and human origin
      in Denmark.
AB  - A classification of the different erm gene classes based on published sequences
      was performed, and specific primers to detect some of these classes designed. The
      presence of ermA (Tn554), ermB (class IV) and ermC (class VI) was determined by
      PCR in a total of 113 enterococcal, 77 streptococcal and 68 staphylococcal
      erythromycin resistant isolates of animal and human origin. At least one of these
      genes was detected in 88% of the isolates. Four isolates contained more than one
      erm gene. ermB dominated among the enterococci (88%) and streptococci (90%) and
      ermC among staphylococci (75%) with ermA (Tn554) present in some isolates (16%).
      Variations in the presence of the different genes when comparing staphylococcal
      isolates of human and animal origin were observed.

PMID- 9919665
TI  - Characterization of surface saccharides in two Corynebacterium diphtheriae
      strains.
AB  - Two Corynebacterium diphtheriae strains were analyzed by assays employing a
      battery of highly purified fluorescent lectins. From 22 lectins tested only seven
      with affinity to receptor molecules containing N-acetylglucosamine (D-GlcNAc), N
      acetylgalactosamine (D-GalNAc), galactose (D-Gal), mannose-like (D-Man-like) and
      sialic acid residues showed positive fluorescent labeling. A higher reactivity of
      Triticum vulgaris (WGA), which binds to sialic acid and/or beta-D-GlcNAc
      containing residues, and Bandeiraea simplicifolia II (BS-II), which recognizes
      alpha and beta-D-GlcNAc units, was shown by the sucrose-fermenting strain.
      Ricinus communis (RCA-I), which recognizes D-Gal units in addition to both
      Glycine max (SBA) and Artocarpus integrifolia (Jacaline) agglutinins that bind to
      D-GalNAc-containing residues, reacted preferentially with the sucrose-negative
      strain. Canavalia ensiformis (Con A), which recognizes D-Man-like receptors,
      reacted with both sucrose-fermenting and non-sucrose-fermenting C. diphtheriae
      biotypes. However, higher interaction was observed with the non-sucrose
      fermenting strain. Fluorescence of WGA binding was significantly decreased by
      neuraminidase treatment suggesting the presence of an exposed sialic acid moiety
      on C. diphtheriae surfaces. Binding assay using radiolabeled [125I]WGA
      essentially confirmed the lectin fluorescence studies. N-Acetylneuraminic acid
      moieties were detected in whole cell hydrolysates as assessed by thin-layer and
      gas-liquid chromatography. The data indicate differences on the cell surface
      saccharide ligands between the sucrose-fermenting and the non-sucrose-fermenting
      C. diphtheriae strains.

PMID- 9919666
TI  - Genetic polymorphism at the beta-tubulin locus among human and animal isolates of
      Cryptosporidium parvum.
AB  - Sequence analysis of a fragment of the beta-tubulin gene was performed on 13
      isolates of the parasite Cryptosporidium parvum, eight from humans and five from
      animals. A total of 12 synonymous substitutions and a deletion of two bases
      within the intron sequence were found. This genetic variation defined two alleles
      at the beta-tubulin locus, which can be identified by a simple polymerase chain
      reaction-restriction fragment length polymorphism assay. A total of 20 isolates
      were also tested using four available molecular markers. These analyses showed
      congruently that the C. parvum isolates segregate into two groups, one found
      exclusively in humans and the other found in both humans and animals. Since no
      recombinant genotypes were observed, the results are consistent with the
      hypothesis of a substantially clonal reproduction in this parasite.

PMID- 9919667
TI  - Phylogenetic re-evaluation of Trametes consors based on mitochondrial small
      subunit ribosomal DNA sequences.
AB  - Mitochondrial small subunit ribosomal DNAs of Cerrena unicolor and Trametes
      consors were sequenced and compared with those of known mushroom taxa. Trametes
      consors is a species recently transferred from Irpex, and Cerrena is a genus
      closely related to Trametes. The present phylogenetic tree showed that Cerrena
      unicolor and Trametes consors clustered together and made an independent lineage
      from the Trametes group. A new combination, Cerrena consors (Berk.) Ko and Jung,
      comb nov., is proposed here by transferring Trametes consors into Cerrena based
      on molecular data along with taxonomic evidence.

PMID- 9919668
TI  - Nisin independent induction of the nisA promoter in Lactococcus lactis during
      growth in lactose or galactose.
AB  - Nisin biosynthesis is autoregulated extracellularly by the mature and modified
      peptide. To investigate other regulatory effects on nisin biosynthesis, a
      transcription fusion of the nisA promoter from Lactococcus lactis ATCC 11454 to
      the promoterless lacZ gene from Streptococcus thermophilus was constructed. This
      fusion construct, pDOC99, expressed beta-galactosidase in L. lactis ATCC 11454
      growing in M17 medium containing glucose (M17G). Consistent with the known model
      for transcription of nisA, pDOC99 did not express beta-galactosidase in the non
      nisin producer, L. lactis LM0230 grown in M17G, unless the nisRK genes (cloned in
      pDOC23) were included in trans and nisin was added to the medium. Growth of this
      strain in M17 containing lactose or galactose, resulted in nisA transcription,
      even in the absence of exogenous nisin. This expression was independent of
      pDOC23. Furthermore, nisA transcription in L. lactis LM0230(pDOC99) grown in M17G
      could be induced by the addition of exogenous galactose, with maximum induction
      occurring at concentrations > 5 mM.

PMID- 9919669
TI  - Characterization of the Acinetobacter baumannii Fur regulator: cloning and
      sequencing of the fur homolog gene.
AB  - Growth kinetics, siderophore activity and iron-regulated bacterial proteins of
      Acinetobacter baumannii BM2580 were studied in iron-restricted and iron
      supplemented chemically defined media. Iron-regulated outer membrane proteins of
      75 kDa and 80 kDa were expressed under iron-restricted conditions. Cloning and
      sequencing of the complete iron-uptake regulatory (fur) gene from A. baumannii
      BM2580 is reported for the first time. This gene is preceded by a single
      autoregulated promoter whose -10 region overlaps the Fur binding site. The open
      reading frame identified encodes a polypeptide consisting of 145 amino acids. The
      fur gene is followed by a divergent open reading frame coding for the C-terminus
      of a putative PilU protein. Sequence analysis indicates that the Fur protein of
      A. baumannii was 63% identical to the Escherichia coli Fur protein.

PMID- 9919670
TI  - Taxonomic status of putative Verticillum alboatrum isolates.
AB  - Two fungal isolates, formerly classified as Verticillium alboatrum and proposed
      as forming the basis of a new sub-group ('Group 2') within the species, have been
      shown to be non-pathogenic to known hosts of V. alboatrum and, on the basis of
      molecular evidence, to be closely related to Verticillium psalliotae and
      Verticillium fungicola. We propose that the taxon V. alboatrum be confined to
      those closely related isolates, usually plant pathogenic and usually producing
      dark resting mycelium, referred to by other authors as Group 1. The only sub
      specific groupings which appear valid (based on pathological and molecular
      evidence) comprise: (1) host-adapted isolates from lucerne; and (2) all other
      isolates.

PMID- 9919671
TI  - A NusG-like transcription anti-terminator is involved in the biosynthesis of the
      polyketide antibiotic TA of Myxococcus xanthus.
AB  - The antibiotic TA of Myxococcus xanthus is synthesized through a type I
      polyketide synthase mechanism. Previous studies have indicated that several genes
      essential for TA production are clustered within a 40-kb region and are
      transcriptionally co-regulated. In this study, we report the genetic analysis of
      the first gene in the TA gene cluster, identified as a NusG-like transcription
      anti-terminator. Functional analysis of this NusG-like anti-terminator gene by
      specific gene disruption confirms that it is essential for TA production but not
      for normal growth and development.

PMID- 9919672
TI  - A new gel tube method for the direct detection, identification and susceptibility
      testing of bacteria in clinical samples.
AB  - We recently developed a simple new method which is designed to separate and
      concentrate bacteria from a sample by centrifugation in a gel system. Bacterial
      enzyme activity is then detected inside the gel without further manipulation
      using a colorimetric or fluorogenic substrate. The method provides a rapid,
      direct means of detecting bacteria in clinical samples, dispensing with the 24-h
      period normally required to isolate colonies on agar. Various applications of the
      method are described below, e.g. screening of negative urine samples,
      identification of Escherichia coli in urine samples, identification of
      Staphylococcus aureus in blood culture broths and detection of oxacillin
      resistant S. aureus in blood culture broths. The advantages of the gel system and
      other applications are discussed.

PMID- 9919673
TI  - Purification and characterization of an Aeromonas caviae metalloprotease that is
      related to the Vibrio cholerae hemagglutinin/protease.
AB  - A zinc metalloprotease (AP34) from Aeromonas caviae was purified by ammonium
      sulfate precipitation and subsequent gel filtration through Sephadex G-100 and
      Sephadex G-50 Superfine. The molecular mass was estimated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis to be 34 kDa. The protease showed
      maximum activity at pH 7.0 and was stable at 60 degrees C. AP34 was completely
      inactivated by EDTA and Zincov. The N-terminal amino acid sequence of AP34 showed
      a high degree of homology with a range of proteases within the family
      Vibrionaceae, including the hemagglutinin/protease (HA/P) of Vibrio cholerae.
      Immunologic relatedness of AP34 and HA/P was demonstrated by Western blotting.
      AP34-like protease was widely distributed among the aeromonad strains.

PMID- 9919674
TI  - Sequence analysis of a cryptic plasmid from Flavobacterium sp. KP1, a
      psychrophilic bacterium.
AB  - A cryptic plasmid found at high copy number was isolated from Flavobacterium sp.
      KP1, a psychrophilic Gram-negative bacterium, cloned, and sequenced. The sequence
      will appear in the DDBJ/EMBL/GenBank databases under the accession number
      AB007196. The pFL1 plasmid is 2311 nucleotides in length with 32.7% GC content,
      and shows a distinctive nucleotide sequence without homology to other plasmids of
      similar length. The plasmid contains two open reading frames of significant
      length, ORFI and ORFII. ORFI encodes a protein similar to the replication
      proteins found in Gram-negative bacterial plasmids, Bacteroides fragilis plasmid
      pBI143 and Zymomonas mobilis plasmid pZM2. The putative translation product of
      ORFII shows homologies with plasmid recombination proteins found mainly in Gram
      positive bacterial plasmids such as Staphylococcus aureus plasmid pT181.

PMID- 9919675
TI  - Transduction of multiple drug resistance of Salmonella enterica serovar
      typhimurium DT104.
AB  - Epidemic strain Salmonella typhimurium DT104 is characterized by various
      multiresistance patterns. At least some of the resistance genes are organized as
      integrons. Resistance genes of DT104 isolates can be efficiently transduced by
      P22-like phage ES18 and by phage PDT17 which is released by all DT104 isolates so
      far analyzed. Cotransduction tests demonstrate that the resistance genes,
      although not organized in a unique integron, are tightly clustered on the
      Salmonella chromosome. The spread of resistance genes in this strain by
      generalized transduction is discussed.

PMID- 9919676
TI  - Viable, but non-culturable, state of a green fluorescence protein-tagged
      environmental isolate of Salmonella typhi in groundwater and pond water.
AB  - An environmental isolate of Salmonella typhi was chromosomally marked with a gfp
      gene encoding green fluorescence protein (GFP) isolated from Aequorea victoria.
      The hybrid transposon mini Tn5 gfp was transconjugated from E. coli to S. typhi,
      resulting in constitutive GFP production. The survival of S. typhi GFP155
      introduced into groundwater and pond water microcosms was examined by GFP-based
      plate counts, total cell counts, and direct viable counts. A comparison between
      GFP-based direct viable counts and plate counts was a good method for verifying
      the viable, but non-culturable (VBNC), state of S. typhi. The entry into a VBNC
      state of S. typhi was shown in all microcosms. S. typhi survived longer in
      groundwater than in pond water as both a culturable and a VBNC state.

PMID- 9919677
TI  - An efficient microbiological growth medium for screening phosphate solubilizing
      microorganisms.
AB  - A novel defined microbiological growth medium, National Botanical Research
      Institute's phosphate growth medium (NBRIP), which is more efficient than
      Pikovskaya medium (PVK), was developed for screening phosphate solubilizing
      microorganisms. In plate assay the efficiency of NBRIP was comparable to PVK;
      however, in broth assay NBRIP consistently demonstrated about 3-fold higher
      efficiency compared to PVK. The results indicated that the criterion for
      isolation of phosphate solubilizers based on the formation of visible halo/zone
      on agar plates is not a reliable technique, as many isolates which did not show
      any clear zone on agar plates solubilized insoluble inorganic phosphates in
      liquid medium. It may be concluded that soil microbes should be screened in NBRIP
      broth assay for the identification of the most efficient phosphate solubilizers.

PMID- 9919678
TI  - Changes in the microbial community in Japan Trench sediment from a depth of 6292
      m during cultivation without decompression.
AB  - A sample of deep-sea sediment was obtained from the Japan Trench at a depth of
      6292 m using a pressure-retaining sediment sampler. Microorganisms in the
      sediment sample were cultivated in marine broth 2216 at ambient pressure (65 MPa)
      without decompression, and at atmospheric pressure (0.1 MPa) as a control
      experiment. 16S ribosomal RNA genes (rDNA) were amplified by PCR from DNA
      extracted from the original sediment sample and the mixed cultures, and the
      nucleotide sequences were determined. The results of phylogenetic analysis based
      on 16S rDNA sequences indicated that microbial diversity in the original sediment
      samples showed a wide distribution of types in the domain Bacteria. Furthermore,
      in the mixed cultures incubated at 65 MPa without decompression, bacterial
      strains belonging to the Shewanella barophiles branch and the genus Moritella
      existed together at the beginning of cultivation, and Moritella strains became
      dominant towards the end of the cultivation period. Finally, in the mixed
      cultures incubated at atmospheric pressure, strains belonging to the genus
      Pseudomonas were dominant at all times. Analysis of fatty acids extracted from
      the cultures supported the phylogenetic results.

PMID- 9919679
TI  - Evidence that Tn5565, which includes the enterotoxin gene in Clostridium
      perfringens, can have a circular form which may be a transposition intermediate.
AB  - The Clostridium perfringens enterotoxin gene is on a transposon-like element,
      Tn5565, integrated in the chromosome in human food poisoning strains. The
      flanking IS elements, IS1470 A and B, are related to IS30. The IS element found
      in the transposon, IS1469, is related to IS200 and has been found upstream of cpe
      in all Type A strains. PCR and sequencing studies from cell extracts and plasmid
      isolations of C. perfringens indicate that Tn5565 can form a circular form with
      the tandem repeat (IS1470)2, similar to the transposition intermediates described
      for a number of IS elements.

PMID- 9919680
TI  - Characterisation of crude oils by carbon and sulphur isotope ratio measurements
      as a tool for pollution control.
AB  - The potential of carbon and sulphur isotope ratios to group crude oils with
      respect to their origin was investigated. Sample selection was based on the
      actual crude oil imports to Germany. Analysed crude oils from Algeria, the
      Community of Independent States (CIS), Middle East, Nigeria, the North Sea and
      Venezuela make up over 86% of the German crude oil imports. The oil as received
      was deasphalted and the maltene fraction was separated by MPLC into saturated,
      aromatic and polar fractions. Due to overlapping areas, it is not possible to
      group the crude oils by their delta 13C values alone. A complete grouping of the
      crude oils with respect to their origin can only be achieved by the combined use
      of delta 13C and delta 34S of crude oils, and isotope type-curves. In some cases
      isotope type-curves enable differentiation between different oil fields of the
      same geographical origin. In order to determine the post-spill changes of delta
      13C values, an experimental spill of crude oil was studied over a period of seven
      weeks in an outdoor aquarium containing pond water. The delta 13C measurements of
      crude oil fractions showed changes up to 1.1/1000 during the oil spill
      simulation. The delta 13C values of the polar fraction exhibited the smallest
      change, with a variation of 0.3/1000, and are therefore especially useful for the
      characterisation of crude oil spills.

PMID- 9919681
TI  - Biokinetic studies in humans with stable isotopes as tracers. Part 1: A
      methodology for incorporation of trace metals into vegetables.
AB  - The metabolism and biokinetics of trace metals in humans can be successfully
      studied employing stable isotopes of the investigated elements as tracers. For
      the estimation of the bioavailability and the intestinal absorption from solid
      food, materials are required which have been intrinsically labelled with the
      chosen stable tracer, since the use of an extrinsic label may lead to erroneous
      results. Here a technique for producing intrinsically labelled vegetables is
      presented and optimized with regard to molybdenum, gadolinium and ruthenium,
      elements of interest in the field of radiation protection and/or nutrition. These
      feasibility studies were aimed to determine the most favourable conditions for
      the production of vegetables containing the selected tracers in amounts high
      enough to enable successful biokinetic studies in humans. In this optimization
      study the natural elements were used instead of the more expensive stable
      isotopes. Mo is readily absorbed both into cress (Lepidium sativum) and into
      french beans (Phaseolus vulg. var. nanus). Gd uptake into cress is moderate,
      while Ru may be easily and successfully incorporated only into sprouts of mung
      beans (Vigna radiata).

PMID- 9919682
TI  - Biokinetic studies in humans with stable isotopes as tracers. Part 2: Uptake of
      molybdenum from aqueous solutions and labelled foodstuffs.
AB  - Molybdenum (Mo) has been identified as an essential trace mental for humans. The
      present study was aimed at the assessment of data on intestinal Mo absorption
      from aqueous solutions and from foodstuffs in humans applying the methodology for
      intrinsic labelling described in Part 1. The intestinal absorption of Mo was
      investigated by means of a double tracer method in 3 healthy volunteers on a
      total of 15 occasions. When administered as aqueous solution, almost complete
      uptake of Mo was observed up to doses of 1 mg and only a slight decrease for
      higher doses. But addition of black tea reduces the absorbed fraction by about a
      factor of ten. Studying Mo absorption from food, intrinsically labelled cress
      showed a reduced uptake as compared to extrinsically labelled cress and aqueous
      solutions. Even less Mo was absorbed from an extrinsically labelled composite
      meal. The data obtained demonstrate a pattern of intestinal Mo absorption which
      is different from that of other essential trace metals, e.g., Fe or Co.

PMID- 9919683
TI  - 18O exchange in suspensions of red blood cells: determination of parameters of
      mass spectrometer inlet system.
AB  - A membrane inlet system to a mass spectrometer (MIMS) allows us to monitor the
      abundance of 18O in CO2 during the exchange of 18O between HCO3-, dissolved CO2
      and H2O that occurs after dissolving 18O-labelled NaHCO3 in aqueous solution.
      Using a mathematical model we quantitate intracellular carbonic anhydrase
      activity and membrane permeabilities for HCO3-, CO2 and H2O of isolated cells or
      intact epithelia added to the solution. For these calculations it was necessary
      to determine (a) the relation between MS signal and [C18O16O], (b) MIMS response
      kinetics and (c) CO2 leakage during the experiment. The three parameters were
      determined by stepwise addition of HCl to HCO3- solution: (a) was found to be
      linear, (b) response times were 7.5 +/- 2s (10 degrees C), 4.5 +/- 1s (20 degrees
      C), 3.5 +/- 0.6s (37 degrees C), and (c) CO2 leakage was < 1/1000 s-1.

PMID- 9919684
TI  - Simultaneous determination of plasma enrichments of 1-13C- and 15N-labelled
      phenylalanine and tyrosine.
AB  - A methylchloroformate derivative was used for the simultaneous determination of
      plasma enrichments of 1-13C-phenylalanine, 1-13C-tyrosine, 15N-phenylalanine and
      15N-tyrosine by gas chromatography/mass spectrometry. All four tracer enrichments
      could be measured in a single GC run. A specific ion fragment was obtained for
      each tracer. This approach allowed an easy determination of the "tracer to tracee
      ratios". Each ion fragment could be measured with an appropriate single-to-noise
      ratio and precision in samples obtained from 100 microliters plasma. The
      derivatization consists of a fast one-step reaction. Therefore it is well suited
      for studies involving a large number of samples, such as non-steady state bolus
      studies.

PMID- 9919685
TI  - Power spectral analysis of short-term RR interval and arterial blood pressure
      oscillations in the lizard, Gallotia galloti: effects of sympathetic blockade.
AB  - The role of the sympathetic limb of the autonomic nervous system (ANS) in the
      mediation of oscillations in consecutive beat-to-beat RR interval (RRI) and
      systolic blood pressure (SBP) values of lizards, Gallotia galloti, was
      investigated using spectral analysis and measuring effects of autonomic blockers.
      alpha-Adrenergic blockade decreased the power spectral density (PSD) of both RRI
      and SBP very low frequency (VLF: 0.007-0.055 Hz) and low frequency (LF: 0.055
      0.150 Hz) bands, whereas beta-adrenergic blockade increased the PSD of both RRI-
      and SBP-VLF and RRI- and SBP-LF bands. These findings suggest that in lizards 1)
      the VLF and LF peaks of RRI and SBP power spectra are alpha-adrenergic mediated,
      and that 2) the beta-adrenergic activity of the sympathetic system may act
      buffering all RRI and SBP oscillations below 0.150 Hz. These results, when
      analyzed jointly with the ones obtained from a previous study (De Vera and
      Gonzalez. 1997. Comp Biochem Physiol 85A:389-394) on the effects of
      parasympathetic blockade on lizards' RRI and SBP oscillations, demonstrate that
      these reptiles, like mammals, exhibit spontaneous short-term oscillations in
      their HR and SBP which are mediated by the ANS. However, unlike mammals, the RRI
      and ABP low-frequency oscillations in Gallotia seem to be similarly affected by
      the ANS and appear to be powered by alpha-adrenergic and parasympathetic
      activities and buffered by beta-adrenergic activity.

PMID- 9919686
TI  - Physiological color change in the bullfrog, Rana catesbeiana.
AB  - Adults of Rana catesbeiana maintained for 4 days in 12:12 light/dark regimen
      exhibited a rhythmic color change of 24 hr. Under constant light, however, the
      rhythm disappeared, and the reflectance values gradually became greater, that is
      the animals became lighter. Under constant darkness, the rhythm was also
      abolished, but the animals tended to a darker color. On black background the skin
      darkening proceeded at a faster rate as compared to the skin lightening of
      animals adapting to a white background. The difference in color change rate
      suggests that the darkening responses are probably mediated by an increase in a
      circulating hormone, whereas skin lightening probably results from the serum
      level decrease of the same hormone. Most certainly, this hormone is alpha-MSH, as
      the in vitro assays demonstrated its high potency as a full darkening agonist
      (EC50 = 9 x 10(-10) M). Prolactin (EC50 = 7.7 x 10(-8) M) and endothelins 2 (EC50
      = 1.3 x 10(-6) M) and 3 (EC50 = 4.8 x 10(-7) M) were also full agonists, but 100-
      to 1000-fold less potent than alpha-MSH. Isoproterenol, in the absence or
      presence of dibenamine, and endothelin-1 also elicited darkening responses in a
      dose-related manner, but reaching only 23% and 35% of the maximal darkening,
      respectively. Isoproterenol darkening effect was completely blocked by
      propranolol, confirming its action through beta-adrenoceptors. These results,
      taken together with the lack of lightening activity of norepinephrine on alpha
      MSH-darkened skins, suggest that R. catesbeiana melanophores do not possess very
      active beta-adrenoceptors and lack alpha-adrenoceptors. On the other hand, the
      lightening agonist melatonin elicited only half-maximal dose-dependent reversal
      of MSH-induced darkening. Our results suggest that the chromatic rhythm is not
      endogenous, and most likely is determined by the light/dark cycle effect on alpha
      MSH secretion.

PMID- 9919687
TI  - Hepatocyte growth factor stimulates chemotactic response in mouse embryonic limb
      myogenic cells in vitro.
AB  - In this study we investigate the influence of Hepatocyte Growth Factor (HGF) on
      the motility of embryonic forelimb myoblasts. Using Blindwell chemotactic
      chambers, it was found that HGF at concentrations of 1-50 ng/ml dramatically
      enhanced the ability of myogenic cells to migrate. This stimulatory effect was
      elicited in a dose-dependent fashion and the effect was reversed with the
      addition of HGF neutralizing antibodies. A checkerboard analysis was performed
      and it revealed that HGF's effect on limb myoblast motility was through both
      chemokinesis and chemotaxis. HGF was also examined for its ability to stimulate
      myogenic cell proliferation, using MF20 antibody as the myogenic marker. At all
      concentrations tested, HGF did not stimulate an overall increase in the numbers
      of MF20-positive myoblasts in culture. To examine the chemokinetic effect of HGF
      on cell migration in the limb, cells were isolated from the proximal regions of
      the limb (areas rich in myogenic cells), exposed to HGF, labeled with DiI and
      transplanted into 11.5 day mouse forelimbs. After 36 h of culture, it was found
      that DiI-labeled limb cells, pretreated with HGF, migrated significantly further
      in the limb than labeled cells that have not been exposed to HGF. The chemotactic
      effect of HGF was also investigated by implanting beads loaded with and without
      HGF into the 11.5 day limb. Proximal to the beads, DiI-labeled limb cells were
      also transplanted. It was found that HGF was able to chemotactically attract and
      direct the migration of DiI-labeled limb cells. Immunohistological staining was
      performed with HGF antibodies to determine the distribution of HGF in the 11.5
      day mouse forelimb. It was found that HGF was strongly expressed by the apical
      ectodermal ridge (AER), the ectoderm and the mesenchyme directly beneath the AER.
      Positive staining was also obtained for the myogenic regions. However, the
      pattern was heterogeneous--punctuated with myogenic cells expressing and not
      expressing HGF.

PMID- 9919688
TI  - Relationship between light intensity and phase resetting in a mammalian circadian
      system.
AB  - The light-induced phase-resetting response of the locomotor activity rhythm in
      the field mouse Mus booduga was studied at two phases of the circadian cycle
      known to respond to light stimuli of 15 min duration and 1000 lux intensity with
      maximum advance (at circadian time 20 [CT20]) and maximum delay phase-shifts (at
      CT15). The phase-shifts evoked by natural daylight stimuli of various
      illuminations ranging between 0.001 lux and 10,000 lux and lasting 15 min were
      estimated. The results clearly demonstrate that the relationship between the
      phase-shifts and the intensities of light stimuli is nonlinear. Furthermore, a
      single light stimulus of 0.001 lux, or 0.1 lux intensity for a duration of 15
      min, administered at CT20, evoked unequivocal responses; phase delays were
      observed instead of phase advances. The critical intensities needed for light
      stimuli of 15 min duration to induce saturating response were calculated and were
      found to be about 100 lux for CT20 and about 500 lux for CT15. These results
      suggest that a greater intensity of light is required at the phase CT15 to induce
      a saturating phase shift than is required at a later phase of the circadian cycle
      (CT20).

PMID- 9919690
TI  - Allocation of inner cell mass and trophectoderm cells to the preimplantation
      blastocyst of the domestic ferret, Mustela putorius furo.
AB  - The growth of ferret preimplantation blastocysts in vivo, collected between 156
      and 240 hr post coitum, was investigated. A technique, combining immunosurgery
      and differential fluorochrome staining, was used to discriminate between inner
      cell mass (ICM) and trophectoderm (TE) cells. Using the stains propidium iodide
      and bisbenzimide (Hoechst 33342), the ICM was stained blue and the TE was stained
      pink. The ICM and TE counts for 90 blastocysts, respectively, averaged 25 and 63
      at 156 hr and increased exponentially to 2077 and 4137 at 240 hr. The Box-Cox
      procedure was used for choosing a transformation that minimized the error sum of
      squares for a linear regression of Y (cell count) on X (time in hr). Logarithmic
      transformations of the ICM, TE and total cell count gave a good fit, but the
      following equations obtained by the Box-Cox procedure provided the best fit,
      where Y is cell count and X is time in hours. For inner cell mass: Y = [(176.06 +
      2.45X)/-899.44 + 1]-3.33; trophectoderm: Y = [(301.38 + 14.48X)/-6863.42 + 1]-10;
      and total: Y = [(2266.97 + 17.0X)/-7837.21 + 1]-5. The R2 values were 0.73, 0.84,
      and 0.84, respectively. The exponential growth of the ferret embryo during the
      time interval that measurements were made fits the general pattern described for
      other mammalian embryos. This report is the first to characterize the pattern of
      cell allocation and growth in preimplantation blastocysts of the ferret, and the
      first such report for a carnivore. The pattern of in vivo development provides a
      standard for judging the quality of in vitro produced and matured ferret embryos
      and, concomitantly, a means to evaluate culture systems.

PMID- 9919691
TI  - Global motion cues and the chromatic system.
AB  - The capacity of the isolated chromatic system to perceive global motion was
      tested in a 40-deg visual field by use of random-dot kinematograms. The method of
      equivalent cone contrasts was used to directly compare the chromatic and the
      achromatic systems. The minimum number of dots necessary to correctly identify
      the motion direction was on the order of 20% for the isochromatic conditions,
      whereas thresholds were rarely obtained in the chromatic conditions. For both the
      isochromatic and the chromatic conditions, the central visual field was the most
      sensitive area, whereas the periphery was slightly less sensitive. This study
      suggests that the chromatic system does not efficiently integrate local motion
      cues to generate a global motion percept.

PMID- 9919689
TI  - Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice.
AB  - The mammalian Hox genes encode a family of conserved transcription factors that
      control the establishment of the body plan during embryogenesis. Many Hox genes
      are also known to be expressed in hematopoietic cells. We found that Hoxc-8, a
      member of the Hox C cluster, is expressed in the mouse hematopoietic organs,
      fetal liver and adult bone marrow. To determine the role of Hoxc-8 gene in
      hematopoiesis, we compared progenitor cell numbers in the fetal liver and adult
      bone marrow cells. We observed a significant reduction in the number of erythroid
      burst-forming unit (BFU-E) and in granulocyte/macrophage colony-forming unit (CFU
      GM) in the Hoxc-8 null mice, although the peripheral blood cell counts were
      normal. The hematopoietic cells from the homozygote animals exhibited normal
      expansion capability in a liquid culture system, suggesting that the decreased
      number of progenitor cells may be due to a defect extrinsic to the hematopoietic
      cells, such as in the interaction with the microenvironment.

PMID- 9919692
TI  - Hilbert-space Karhunen-Loeve transform with application to image analysis.
AB  - A generalization of the Karhunen-Loeve (KL) transform to Hilbert spaces is
      developed. It allows one to find the best low-dimensional approximation of an
      ensemble of images with respect to a variety of distance functions other than the
      traditional mean square error (L2 norm). A simple and intuitive characterization
      of the family of Hilbert norms in finite-dimensional spaces leads to an algorithm
      for calculating the Hilbert-KL expansion. KL approximations of ensembles of
      objects and faces optimized with respect to a norm based on the modulation
      transfer function of the human visual system are compared with the standard L2
      approximations.

PMID- 9919693
TI  - Simulation of scanning laser techniques for optical imaging of blood-related
      intrinsic signals.
AB  - Optical imaging of intrinsic signals detects neural activation patterns by taking
      video images of the local activity-related changes in the light intensity
      reflected from neural tissue (intrinsic signals). At red light (605 nm), these
      signals are caused mainly by local variations of the tissue absorption following
      deoxygenation of blood. We characterize the image generation process during
      optical imaging by Monte Carlo simulations of light propagation through a
      homogeneous model tissue equipped with a local absorber. Conventional video
      imaging and scanning laser imaging are compared. We find that, compared with
      video imaging, scanning laser techniques drastically increase both the contrast
      and the lateral resolution of optical recordings. Also, the maximum depth up to
      which the signals can be detected is increased by roughly a factor of 2 when
      scanning laser optical imaging is used. Further, the radial profile of the
      diffuse-reflectance pattern for each pixel is subject to changes that correlate
      with the depth of the absorber within the tissue. We suggest a detection geometry
      for the online measurement of these radial profiles that can be realized by
      modifying a standard scanning laser ophthalmoscope.

PMID- 9919694
TI  - Ternary pseudorandom encoding of Fourier transform holograms.
AB  - Pseudorandom encoding is a statistical method for designing Fourier transform
      holograms by mapping ideal complex-valued modulations onto spatial light
      modulators that are not fully complex. These algorithms are notable because their
      computational overhead is low and because the space-bandwidth product of the
      encoded signal is identical to the number of modulator pixels. All previous
      pseudorandom-encoding algorithms were developed for analog modulators. A less
      restrictive algorithm for quantized modulators is derived that permits fully
      complex ranges to be encoded with as few as three noncollinear modulation values
      that are separated by more than 180 degrees on the complex plane.

PMID- 9919695
TI  - Zoogeographical implications of variation in mitochondrial DNA of Arctic grayling
      (Thymallus arcticus).
AB  - Most of the northern half of North America's freshwater fish survived the last
      glacial period in unfrozen refugia peripheral to the ice sheets. In our study,
      the question of which refugia Arctic grayling (Thymallus arcticus) inhabited
      during the Wisconsinan Ice Age, and how they subsequently dispersed to their
      present geographical range, was examined using mitochondrial DNA (mtDNA)
      analysis. mtDNA from 12 T. arcticus populations was analysed by direct sequencing
      and restriction fragment length polymorphism analysis (RFLP). Our data support
      the hypotheses that T. arcticus had a large refugial population in the Bering
      Refuge (shown by high mtDNA diversity in extant Alaskan populations) and that
      British Columbia was colonized from the Bering Refuge (shown by mtDNA haplotype
      similarities). Our data also show that a disjunct southern set of populations in
      Montana is significantly different from the northern grayling, in terms of
      restriction haplotype frequency and distinguishing sequence characteristics.
      Sequence results yielded an estimated divergence time of 370,000 years between
      the northern and Montana grayling haplotypes. We conclude that T. arcticus
      survived the Wisconsinan glaciation in at least two refugia: (i) the Bering
      Refuge north of the ice sheets; and (ii) either the Upper Missouri or the
      southwest Alberta Refuge, south of the ice sheet.

PMID- 9919696
TI  - Intrasporal variability of ribosomal sequences in the endomycorrhizal fungus
      Gigaspora margarita.
AB  - The sequence variability of the ribosomal internal transcribed spacer (ITS)
      region, which comprises the 5.8 gene and the flanking regions ITS1 and ITS2, was
      investigated in the arbuscular mycorrhizal fungus Gigaspora margarita. DNA
      analysis of a multispore preparation and three single spores led to the
      identification of 11 slightly different sequences (three variants within a single
      spore), indicating substantial intersporal and intrasporal genetic variability
      (up to 9% sequence divergence). The sequence variations inside a single spore may
      be higher than that observed between spores. Even so, primers designed on the
      ITS1 and ITS2 regions identified Gi. margarita isolates and detected the
      endophyte during colonization.

PMID- 9919698
TI  - PCR-restriction fragment length polymorphism (RFLP) analyses reveal both
      extensive clonality and local genetic differences in Candida albicans.
AB  - Using a polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method to obtain genotypes for the diploid pathogenic yeast, Candida
      albicans, we analysed 204 C. albicans isolates from three populations of the Duke
      University community: two from clinical sources [one from patients infected with
      human immunodeficiency virus (HIV) and the other from patients without HIV
      infection], and the third from healthy student volunteers. The results indicated:
      (i) extensive evidence for clonality within and between populations of C.
      albicans; and (ii) greater genotypic and gene diversities in the nonclinical
      population than those derived from clinical specimens, regardless of HIV status.
      The two clinical populations were genetically more similar to each other than
      either was to the population consisting of isolates from healthy people. Within
      each population sample there was a general lack of heterozygotes, and random
      associations of alleles within and between loci were found in less than 50% of
      the loci or pairs of loci. These findings were consistent between the two sets of
      samples analysed: those including all isolates and those including only clone
      corrected isolates. Possible mechanisms are presented to explain the observed
      patterns of genetic variation within and between C. albicans populations.

PMID- 9919697
TI  - Genetic variation, population structure and cryptic species within the black
      mudfish, Neochanna diversus, an endemic galaxiid from New Zealand.
AB  - To investigate the phylogenetic relationships and geographical structure among
      landlocked populations of the black mudfish, Neochanna diversus, mitochondrial
      DNA nucleotide sequence data were sampled from seven populations from the Waikato
      and Northland regions of New Zealand. The complete D-loop region was sequenced
      from 70 individuals, with 913 bp from the tRNA-pro end used in population and
      phylogenetic analysis. A tandem repeat array, which ranged in size up to 200 bp,
      was found in most populations at the 3' end of the D-loop that was not able to be
      aligned for analysis. Of the seven sites sampled, two from Northland exhibited
      significant sequence divergence from all other sites. There was also a clear
      distinction among remaining Northland sites and those from the Waikato. An
      additional 518 bp segment of the 16S region was sequenced from all sites and
      compared with the other New Zealand mudfish species, N. apoda, N. burrowsius and
      the Tasmanian mudfish Galaxias (Neochanna) cleaveri using Galaxias maculatus as
      an outgroup. Both D-loop and 16S sequence data provided strong evidence for a
      cryptic species of mudfish present in Northland. The significant genetic
      structure apparent in the black mudfish appears most probably to be attributed to
      geological conditions during the Pliocene, where peat wetlands became apparent in
      the Waikato while Northland consisted of disjunct 'islands'. Conservation and
      management of these populations must take into account the historical processes
      that have shaped these patterns of genetic diversity.

PMID- 9919700
TI  - Population subdivision among desert bighorn sheep (Ovis canadensis) ewes revealed
      by mitochondrial DNA analysis.
AB  - We used behavioural observations and mitochondrial DNA (mtDNA) sequence analysis
      to examine demographic and genetic structure within and among home-range groups
      of desert bighorn sheep (Ovis canadensis) ewes in the Peninsular Ranges of
      southern California, USA. We identified substantial genetic variation in the
      first 515 bp of the mtDNA control region and determined that seven haplotypes
      were distributed in a nonrandom fashion among these ewe subpopulations. Although
      a significant (P < 0.01) amount of mtDNA variation (33%) was partitioned among
      home-range groups, we did not find strong evidence for matrilineal substructuring
      within these groups. Based on analyses of molecular variance, and comparisons of
      behavioural associations and distances between centres of activity, we concluded
      that within a given home-range group, bighorn sheep ewes generally associate with
      other ewes based on their availability rather than their matrilineal
      relationships. Our results also supported the conclusion that multiple ewe
      subpopulations exist within the Peninsular Ranges, and that these subpopulations
      are the most basic demographic and genetic units.

PMID- 9919702
TI  - Nuclear insertion sequences of mitochondrial DNA predominate in hair but not in
      blood of elephants.
AB  - Hair has become a widely used source of DNA in population genetics, forensics,
      and conservation biology. Here were report that PCR primers that amplify a
      segment of the mitochondrial control region from blood DNA amplify primarily
      integrated nuclear copies of mitochondrial DNA from hair DNA. Thus, in some
      species, and under some circumstances, DNA from hair may yield unreliable
      results.

PMID- 9919703
TI  - Genetic evidence for a recent origin by hybridization of red wolves.
AB  - Genetic data suggest that red wolves (Canis rufus) resulted from a hybridization
      between coyotes (C. latrans) and grey wolves (C. lupus). The data of the
      hybridization, however, is uncertain. According to one hypothesis, the two
      species came into contact as coyotes increased their geographical range in
      conjunction with the advance of European settlers and as grey wolves were
      extirpated from the American south. Alternatively, the red wolves could have
      originated tens of thousands of years ago as a result of climate and habitat
      changes that disturbed the ecology of the two parent species. To obtain an upper
      limit on the date of hybridization that would help to distinguish the two
      scenarios, we compared microsatellite allele length distributions from red
      wolves, coyotes and grey wolves. Subject to the assumptions of our analysis, we
      conclude that the red wolves originated as a result of hybridizations that
      occurred during the past 12,800 years, and probably during the past 2500 years.

PMID- 9919705
TI  - Microsatellite primers for studies of gene flow and mating systems in white-eyes
      (Zosterops).

PMID- 9919704
TI  - Polymorphic microsatellite markers in the western mosquitofish, Gambusia affinis.

PMID- 9919707
TI  - Polymorphic microsatellite DNA markers in the field vole Microtus montebelli.

PMID- 9919709
TI  - Isolation and characterization of microsatellite loci from the endangered beach
      mouse Peromyscus polionotus.

PMID- 9919710
TI  - Performance of a 2k CCD camera designed for electron crystallography at 400 kV.
AB  - We discuss the performance of a charge-coupled device (CCD) camera that has been
      designed for use in electron crystallographic studies of proteins. There have
      been many previous publications describing the characteristics and performance of
      CCD-based cameras in electron microscopy; here we focus on characteristics
      relevant to protein studies at 400 kV. The low exposure that must be used in such
      studies produces a very poor signal-to-noise ratio, so any loss of signal-to
      noise ratio in the recording process must be avoided. Images must contain a
      sufficient number of molecules to allow identification of the reciprocal lattice,
      thus requiring a large image format. Electron diffraction patterns may contain
      some spots with intensity around 10(-7) times that of the central beam, so the
      largest possible dynamic range is helpful. Some of the characteristics we discuss
      are most easily measured with crystals, but the conclusions also apply for other
      work such as single-particle analyses. The camera has been optimized for work at
      400 kV with a P43 scintillator fiber-optically coupled to a CCD with 24 microns
      pixels. The scintillator in this camera is thicker than generally used at lower
      voltages, which provides an adequate signal level but slightly degrades the
      resolution. Operation at 400 kV leads to a point spread function that is broader
      than the CCD pixel size. Images are thus binned by a factor of two to double the
      effective pixel size, with the resulting loss of a factor of two in the size of
      areas that can be recorded in a single frame. A large CCD with a 2048 x 2048
      pixel array is used to compensate for this loss and provide a sufficient signal
      for the crystallographic image processing used in this work. Images and electron
      diffraction patterns recorded on the CCD are compared with data recorded on
      photographic film. While the quality of the images recorded on the CCD at the low
      exposures required in protein studies is not quite as good as that on film,
      electron diffraction data recorded on the CCD are superior to that on film.

PMID- 9919711
TI  - Central cholinergic nervous system and cholinergic agents.
AB  - Central cholinergic nervous system play important role in many physiological and
      behavioral functions in humans. The activity of the cholinergic nervous system
      depends upon the production and fate of acetylcholine and all compounds
      influenced its biosynthesis, storage, release, hydrolysis, interaction with
      different subtypes of cholinergic receptors, etc., there are very important drugs
      and therapeutics. This paper summarizes current views on many compounds which can
      interact with different parts of central cholinergic nervous system.

PMID- 9919712
TI  - Proto-surgery in ancient Egypt.
AB  - This article investigates the evidence we have for the existence of proto-surgery
      in ancient Egypt during the Dynastic Period (c.3200-323 BC). Climate and chance
      have preserved medical literature as well as paleoarcheological specimens and
      these artefacts, along with extant Greek and Roman treatises appear to support
      the conclusion that proto-surgery was practised in ancient Egypt (the prefix
      proto-designates an original or early form). Elements of proto-surgical
      development including analgesia and sedation, the incision, trephination, proto
      surgery of trauma, mythical proto-surgery and antisepsis, drawing on primary
      sources, surviving artefacts and modern commentary are discussed. Where
      appropriate comparisons are made with proto-surgery in ancient Mesopotamia and
      the Bronze Age Aegean.

PMID- 9919713
TI  - The determination of basal glycemia and glucose tolerance curve: the manners of
      blood sampling.
AB  - There were analyzed the conditions under which the basal glycemia and/or glucose
      tolerance curve is not contaminated by stress induced changes in glycide
      metabolism. When the basal glycemia was monitored, blood was sampled to
      heparinized capillaries from retrobulbar plexus under the light ether anaesthesia
      or by decapitation without narcosis. The animal represented the control for
      itself. No differences was found in basal glycemia under the two mentioned blood
      sampling. In the second series of experiments glycemia was monitored in the time
      schedule which is used in glucose tolerance test, i.e., blood sampling was
      performed 30, 60, 120 and 180 min after the first sampling from retrobulbar
      plexus either under light ether anaesthesia (in 14 h starvated rats or in rats
      with free access to diet) or under Nembutal anaesthesia (in 14 h starvated rats).
      No differences were found in glycemia when two types of narcosis is compared. No
      signs of augmentation were detected. In the last series when blood sampling was
      taken in two sec intervals, time dependent augmentation of stress glucose
      elevation was found. The augmentation was more expressed in the rats with free
      access to diet than in starvated animals.

PMID- 9919715
TI  - Atropine-induced convulsions in the septohippocampal system. I. Effects of
      cannula position and sex.
AB  - Effects of local administration of atropine into the medial septal nucleus (MSN)
      and dorsal septal nucleus (DSN) were tested in laboratory rats. Atropine
      administration led to the development of a spike/wave activity in the hippocampus
      as well as amygdala within 10 minutes. The frequency of spikes ranged in the
      absolute values from 20 to 25 spikes per minute in the case of atropine
      administration to MSN, while in the case of DSN it reached only about 16 spikes
      per minute. Spike/wave activity outlasted in the EEG record within 2 hours. The
      average incidence of spikes was somewhat lower in females than in males. A
      possible relation of the atropine-induced spike/wave activity to another kinds of
      limbic convulsions is discussed.

PMID- 9919716
TI  - A new method of estimation of the optimal AV delay by using pulse oximetry in DDD
      paced patients.
AB  - The paper gives a detailed description of a new method for estimating the optimal
      AV delay in dual chamber paced patients, which is non-invasive, not dependent on
      the examinator, not time consuming and inexpensive. In principle, the pulse
      oximetry signal obtained by common finger probe was used to measure the change in
      its time course after changes in pacemaker stimulation. The Eagle 4000 monitor,
      manufactured by Marquette USA, was used for measurements and digitizing the data
      and then this data was analyzed using a portable personal computer with original
      programs developed in Famulus v. 3.5. Our results were compared to the standard
      method for optimizing AV delay which uses the direct measurement of blood
      pressure in the ascending aorta. Twenty-four patients with Physios pacemakers
      were enrolled in the pilot study. Measurements showed a positive correlation (r =
      0.982, N = 432) between the changes in the pulse oximetry amplitude and changes
      in the pressure pulse amplitude measured in the ascending aorta by a catheter-tip
      manometer. These results indicated that this new method could be a possible
      alternative to the currently used techniques for AV interval optimization.

PMID- 9919714
TI  - Muscle GLUT-4 and insulin binding to erythrocytes and to adipose, liver and
      muscle tissue in genetically hypertensive obese rats and in their lean siblings:
      effect of long lasting terguride treatment.
AB  - Experiments were performed in the genetically hypertensive obese rats of Koletsky
      type (SHR/N-cp) and in their lean siblings of both sexes. Insulin binding to
      erythrocytes and to adipose tissue, lever tissue and muscle tissue was monitored
      in the control animals and in the animals under the long lasting terguride
      treatment. In control animals insulin binding shows substrain and tissue
      dependence being elevated in lean rats except insulin binding to erythrocytes
      where inverse is true. Terguride increases percentage of specific insulin binding
      to erythrocytes in all groups except obese females, terguride increases
      percentage of specific binding to adipose tissue except lean females, the
      mentioned drug remained without effect in muscle tissue in all group except lean
      females where drug induced elevation was detected. The effect of terguride in
      liver tissue was monitored only in males of both substrains, elevation was found
      only in lean. GLUT-4 was analyzed only in muscle tissue. The effect of terguride
      was found in obese females, i.e., in the group which shows reduced GLUT-4
      relative to lean females.

PMID- 9919717
TI  - Surgical treatment of anterior septal deviations.
AB  - Anterior septal deviations are very difficult to handle because their location
      causes valvular obstruction, and any small residual deviation can cause a high
      degree of obstruction. The commonly performed submucous resection is not a
      suitable technique to handle this deformity. The maxilla-premaxilla technique
      offers a better approach. The surgical technique for anterior septal deviation
      differs from the standard septoplasty in several steps. A modified technique to
      treat this particular pathology is described in detail. This technique is highly
      reliable, and simplifies the access to a difficult-to-handle deformity.

PMID- 9919718
TI  - History of hematology at the Charles University, Faculty of Medicine and Faculty
      Hospital in Hradec Kralove.

PMID- 9919719
TI  - Meso-2,3-dimercaptosuccinic acid in the treatment of occupationally exposed lead
      workers.
AB  - The aim of this study was to evaluate the efficacy of meso-2,3-dimercaptosuccinic
      acid (DMSA) treatment in workers with increased lead absorption and no overt
      symptoms of lead poisoning. Seven occupationally lead exposed male workers with
      blood lead concentrations (PbB) exceeding 50 micrograms/100 ml and a positive
      calcium disodium ethylenediaminetetraacetate (EDTA) lead mobilization test were
      treated with DMSA for 19 days. Individual doses were 700 mg DMSA, three times a
      day from day one to five, and twice a day from day six to 19. The treatment
      intensified urinary lead excretion, most rapidly during the first five days. The
      increased elimination was followed by a decline of mean PbB to 15% of the
      pretreatment values. However, 15 days after the treatment, the PbB concentrations
      rebounded, yet kept below the baseline values and did not exceed 40
      micrograms/100 ml. After repeated EDTA lead mobilization test, urine lead was 23
      68% of that before DMSA treatment. It can be concluded that DMSA can effectively
      reduce chelatable lead in occupationally exposed workers.

PMID- 9919720
TI  - Effects of gamma-radiation on ovarian follicles.
AB  - In order to observe the morphological and endocrinological changes of the rat and
      mouse ovarian follicles by gamma-radiation, rats were whole-body irradiated with
      doses of 3.2 Gy and 8.0 Gy and mice with 2.9 Gy and 7.2 Gy. Sections of ovaria
      were examined by light microscopy. Concentrations of progesterone, testosterone,
      and estradiol in ovarian homogenate were determined by radioimmunoassay
      techniques. Gamma-radiation resulted in the increased percentage of atretic
      follicles in the groups killed on day 0, day 4, and day 8 after irradiation. The
      decrease in granulosa cell viability was found in animals killed on day 4 after
      irradiation. The finding of the high ratio of testosterone to estradiol compared
      to that of progesterone to testosterone suggests that aromatase activity--steroid
      biosynthesis from testosterone to estradiol--in granulosa cell could be affected
      by gamma-radiation.

PMID- 9919721
TI  - Emissions and ambient levels of sulphur dioxide in the Rijeka Bay area.
AB  - During the eighties the city of Rijeka was one of the most polluted cities in
      Croatia with sulphur dioxide due to high emission of this pollutant from
      industrial plants. In mid-eighties, annual means of SO2 exceeded 100
      micrograms/m3 in the city centre, in the Bakar Bay area varied between 70-80
      micrograms/m3, while in the suburban residential area they were up to 40
      micrograms/m3. In 1995 annual means were below the guideline value of 50
      micrograms/m3 in the whole Rijeka Bay area. Emission inventory based on 1989 data
      estimated total SO2 emission to approximately 36,000 t a year, 95% of which from
      industrial sources. The update from 1995 data gave a new estimate of
      approximately 11,000 t a year, which is a 70.5% reduction of SO2 emission.
      However, the contribution of emissions from industrial sources remained
      practically unchanged (95%). The emission reduction resulted in the decrease of
      ambient levels of SO2. The paper presents trends in SO2 annual mean
      concentrations in the period 1986-1995 for two urban sites, two sites situated in
      the industrial area east of the city, and a suburban residential site.

PMID- 9919723
TI  - [Use of the Purdue Non-verbal Test in a group of candidates for a driving
      license].
AB  - The Purdue nonverbal test (PNT) was used to analyze intellectual abilities of 500
      candidates for a driving license. The candidates were divided in five age groups
      of 100 subjects in each: 16-19, 20-24, 25-39, 40-54, and over 54. The
      distribution of result differs greatly from the normal distribution (P < 0.01)
      for all age groups of candidates. The distribution of the results of the
      candidates over 54 is positively asymmetric, while the distribution of the
      results of all other age groups is negatively asymmetric. These results suggest
      that the PNT is poor in discrimination. The percentage of candidates categorized
      according to the PNT as "capable for handling a motor vehicle" was higher than
      expected, while the percentage of candidates categorized as of "limited
      capability" was below expectations. According to these criteria, no candidate was
      found "incapable", which is in sharp nonconformity with the expected 5 per cent
      (5%). The above results indicate that the screening of candidates according to
      the criteria of intellectual ability is inadequate because of inadequate
      criteria, especially those which are supposed to determine borderline and lower
      intellectual ability. The results of the research show that admission of
      candidates whose intellectual ability borders or is below intellectual
      insufficiency parameters renders inadequate the prevention of risks in traffic.
      The risk in traffic is expected to increases with every single driving license
      issued to a person whose intellectual ability is inadequate for safe driving.

PMID- 9919722
TI  - [Respiratory function and allergic reactions in paper recycling workers].
AB  - Respiratory function and allergic reactions were studied in 101 male workers in
      paper recycling and in 87 nonexposed male control workers. Ventilatory capacity
      was measured by recording maximum expiratory flow-volume (MEFV) curves with
      readings on forced vital capacity (FVC), one-second forced expiratory volume
      (FEV1), and maximum expiratory flows at 50% and the last 25% (FEF50 and FEF25,
      respectively). Skin prick test with paper dust allergens, some nonoccupational
      allergens, and total immunoglobulin IgE analysis were used to assess
      immunological status. Significantly higher prevalences of all chronic respiratory
      symptoms were recorded in the exposed workers than in controls. The highest
      prevalence was recorded for chronic cough (36.6%), followed by chronic phlegm
      (34.7%), chronic bronchitis (33.7%), sinusitis (31.7%), nasal catarrh (29.7%),
      and dyspnea (16.8%). Occupational asthma was diagnosed in four paper recycling
      workers only (4.0%). Values of FEF50 and FEF25 were significantly lower than
      predicted, indicating obstructive changes located mostly in the smaller airways.
      Skin tests to paper allergens were found positive in 16 (15.8%) paper recycling
      workers and none in controls. An increase in total immunoglobulin IgE was found
      in 21 of 101 paper recycling workers and in two of 37 of controls (P < 0.05). Our
      data indicate that exposure to air pollutants in paper recycling industry may
      lead to the development of respiratory symptoms accompanied by lung function and
      immunological impairment.

PMID- 9919724
TI  - [Multiple chemical sensitivity: theories of etiopathogenesis].
AB  - Multiple chemical sensitivity (MCS) is a controversial disorder of uncertain
      etiology, characterized by recurrent symptoms referable to multiple organ
      systems, occurring as a response to chemically unrelated compounds at doses far
      below those established to cause harmful effects in the general population. The
      fundamental question is whether the MCS is primarily a toxicodynamic phenomenon
      (a pathological interaction between a chemical agent and organ systems, possibly
      acting through a mechanism different from those known in toxicology) or a
      psychogenic disorder (an emotional reaction to perceived toxic agents). This
      paper presents some recent theories of etiopathogenesis of the MCS discussing the
      role of immunological, inflammatory, metabolic, psychophysiologic, and
      neurochemical mechanisms, as well as the role of neural sensitization in the
      etiology of the disorder. The paper foregrounds the complex relation between
      psychiatric disorders and social factors, on one hand, and the MCS on the other.
      A particular emphasis is put on the relevance of the MCS research for clinical
      practice, public health, and regulatory decisions.

PMID- 9919725
TI  - The third revolution.

PMID- 9919726
TI  - The billings ovulation method. What are the benefits?

PMID- 9919727
TI  - Musculoskeletal chest pain.

PMID- 9919729
TI  - Urinary incontinence in the elderly. Establishing a cause may allow a cure.
AB  - BACKGROUND: As people age, urinary incontinence becomes more common. It is
      socially isolating and is often a factor in the move to residential care.
      OBJECTIVE: This article highlights the causes of incontinence in the elderly.
      DISCUSSION: With careful assessment, many elderly people can be cured, and the
      majority significantly helped. The implications of this for social and
      psychological health and the impact on the health and welfare dollar are
      considerable.

PMID- 9919728
TI  - Hepatitis C and the 'cure'.

PMID- 9919730
TI  - Urinary incontinence in the elderly. Managing for maximum outcomes.
AB  - BACKGROUND: As people age urinary incontinence is increasingly prevalent,
      socially isolating and is often a factor in the move to residential care.
      OBJECTIVE: To highlight the options in management. DISCUSSION: With careful
      assessment many elderly can be cured, and the majority significantly helped. The
      implications for social and psychological health and the impact on the health and
      welfare dollar are considerable.

PMID- 9919731
TI  - Vesico ureteric reflux and urinary tract infections in children.
AB  - BACKGROUND: UTIs in children are a common problem in general practice. The
      difficult aspects lie in the management of recurrent UTIs and the further
      investigation and treatment of vesico ureteric reflux. OBJECTIVE: To give some
      insight into the difficulties of the clinical diagnosis and further management of
      UTIs in children of different ages. DISCUSSION: This is a controversial area of
      management in paediatric practice. This article gives an insight into my personal
      approach to these problems, which form a large part of my clinical practice. My
      perspective is that of paediatric urologist working in a tertiary teaching
      hospital. Other people working in this field may take a very different approach.

PMID- 9919732
TI  - Common urological problems in women.
AB  - BACKGROUND: Significant advances in the management of some common urinary
      problems have occurred in recent years. Problems that are likely to present to
      the general practitioner include urinary incontinence, voiding dysfunction,
      recurrent bacterial cystitis and interstitial cystitis. OBJECTIVE: The aim of
      this article is to highlight the advances that have occurred in the management of
      these common problems and their management strategy in the primary care setting.
      DISCUSSION: The management of incontinence, particularly stress urinary
      incontinence includes an accurate diagnosis and treatment tailored to the
      condition identified. Urinary incontinence due to the overactive and/or
      underactive bladder is more difficult to cure but significant improvement can be
      achieved in the majority of people. While severe incontinence requires an
      accurate diagnosis, non-operative strategies without a urodynamic diagnosis can
      be used in the treatment of milder forms. It is important to obtain an accurate
      diagnosis when the patient is not improving with conservative strategies. The
      problem of recurrent bacterial infections is common in women of all ages but cure
      should be possible in the majority of affected women. While the enigmatic entity
      of interstitial cystitis is increasingly recognised in out patients the exact
      basis for this condition remains obscure. Symptomatic improvement is achievable
      to a variable degree in most patients.

PMID- 9919733
TI  - National standards for general practice.
AB  - A set of standards for Australian general practices has been developed through a
      4 year project conducted by The Royal Australian College of General
      Practitioners. An orderly, iterative process was adopted to ensure comprehensive
      consultation with general practitioners, other health professionals, consumers
      and governments. The draft standards were field tested in 199 randomly selected
      urban and rural practices. Results of this field testing showed that the
      standards have content validity, that they can be measured reliably and that the
      practice visit protocol is feasible. The standards are calibrated to define the
      minimum acceptable features of general practices expected for the mid 1990s. The
      standards have been adopted by Australian General Practice Accreditation Limited
      as the basis for a voluntary system of practice accreditation.

PMID- 9919734
TI  - Smoking prevention and cessation in adolescents.
AB  - Tobacco smoking is the most important preventable health risk factor in
      Australia. It has lost popularity and acceptability in Australia as a result of
      public health campaigns and their reinforcement through government legislation.
      The rate of smoking in Australia has gradually declined due to increased
      cessation in adults. Adolescents, however, are smoking as much as ever. The aim
      of this paper is to provide family practitioners with practical, simple clinical
      strategies to reduce teenage smoking.

PMID- 9919735
TI  - Long acting beta agonists.
AB  - Long acting beta agonists (LABAs) such as salmeterol and eformoterol provide 12
      hour bronchodilatation, giving continuous control of asthma symptoms particularly
      at night. More recent evidence also suggests a role as 'steroid-sparing' agents,
      allowing control of asthma at lower doses of inhaled corticosteroids (ICS).
      Providing a sufficient dose of inhaled steroid (in adults around 800 micrograms
      of belcomethasone or budesonide or 400 micrograms of fluticasone) is used in
      conjunction with LABAs, there is no evidence of any increase in asthma
      exacerbation. Cost is the major impediment to the widespread application of these
      useful agents.

PMID- 9919736
TI  - A severe adverse reaction to mefloquine and chloroquine prophylaxis.
AB  - A 23 year old man with no history of neurological or psychiatric illness ingested
      three weekly 228 mg doses of mefloquine base (250 mg salt) as malaria prophylaxis
      while in India. He experienced an increasingly severe adverse reaction after each
      dose, including symptoms of paranoia, hallucinations, and suicidal ideation. The
      man discontinued mefloquine and continued malaria prophylaxis with chloroquine.
      Shortly after the first 300 mg dose of chloroquine base (500 mg chloroquine
      phosphate salt), symptoms acutely intensified and became debilitating. Severe
      symptoms persisted for 12 months following the discontinuation of both
      antimalarial drugs.

PMID- 9919737
TI  - Ankle 'headache'. Part II.

PMID- 9919738
TI  - Is the potassium really elevated?

PMID- 9919739
TI  - Zoonosis. A threat to health.

PMID- 9919740
TI  - Annular skin lesions with a smooth surface.

PMID- 9919741
TI  - [An audit of cardiovascular diseases].

PMID- 9919742
TI  - [Relation between insulin resistance and small, dense lipoproteins with low
      density and the development of atherosclerosis in type 2 diabetes mellitus].
AB  - Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with
      high mortality and morbidity due to macrovascular and microvascular
      complications. CHD mortality and morbidity is 2-3 times higher in diabetic than
      in non-diabetic patients. There are many potentially atherogenic factors in
      diabetes these may underlie this problems. Except major risk factors (high serum
      cholesterol concentration, hypertension, cigarette smoking), insulin resistance
      is common in DM type 2 patients. The dyslipidemic component of insulin resistance
      is "atherogenic lipoprotein phenotype", its components include small LDL
      particles (pattern B) with higher atherogenic risk. Several recent studies have
      demonstrated the preponderance of small, dense LDL in patients with DM type 2 and
      IR. The question of whether small, dense LDL can be explained by triglyceride
      levels alone or whether it is directly related to DM type 2 and insulin
      resistance is still the subject of debate. If serum triglycerides exceed 1.3
      mmol/l, small, dense LDL increases. The practical implication is that serum
      triglyceride levels should be maintained as low as possible to prevent the
      deleterious effects of triglycerides on LDL subclass distribution and size. There
      are several potential mechanisms to explain the increased atherogenicity of dense
      LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation
      leading to its increased uptake by macrophages and subsequent removal by
      scavenger pathway, also has a lower binding affinity to LDL receptors).
      Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias
      would reduce atherosclerosis disease. However, to date, there have been no
      intervention studies specifically designed to test this postulate in the diabetic
      population. Such studies the Diabetes Atherosclerosis Intervention Study (DAIS),
      Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative
      Atorvastatin in Diabetes Study and Lipid in Diabetes Study are currently in
      progress. (Tab. 4, Fig. 2, Ref. 81.)

PMID- 9919743
TI  - [The pre-hospitalization period in acute myocardial infarct].
AB  - The therapy of AMI is aimed at the prevention of death, minimalization of
      discomfort caused by the disease and the reduction of the infarction focus (as
      soon and as markedly as possible) since the success of this step links with the
      later short-term as well as the long-term prognoses of the patient. (Tab. 2, Ref.
      15.)

PMID- 9919744
TI  - [Prognostic significance of biochemical markers in acute coronary syndromes].
AB  - The article reviews the possibilities of biochemical markers in coincidence with
      the assessment of prognosis in acute coronary syndromes and in the revealing of
      effectivity of their therapy. The current options of clinical biochemistry in
      many cases allow to supplement, confirm, or exclude the results of modern
      physical and other clinical examination methods and in this way to contribute to
      the accuracy of the diagnostic process, and enable to comment the prognosis and
      the risk measure of the patient. A significant progress has been achieved in the
      assessment of effectivity in thrombolytic therapy in acute myocardial infarction,
      where especially the series assessment of myoglobin levels or specific troponin
      cardiomarkers can facilitate the process of physician's decision as to the
      assessment of the subsequent procedure in the treatment of patients. The
      assessment of levels of both specific and partly less specific cardiomarkers
      becomes one of the criteria of the decision in coincidence with ischaemic
      episodes in the peri and postoperative periods (the diagnosis of peri-operative
      myocardial infarction). Specific troponin cardiomarkers acquire an extraordinary
      significance in the prediction of the measure of risk in patients with unstable
      angina pectoris where already one single assessment of the level of these markers
      is sufficient for hospitalization of the patient and thus enables to change the
      physician's strategy of further therapy. (Ref. 95.)

PMID- 9919745
TI  - [Thrombolytic therapy in acute myocardial infarct].
AB  - The data gained from clinical studies in the past years have indicated that the
      thrombolytic therapy (TL) has favourable effect on patients with acute myocardial
      infarction (AMI). It is aimed at reperfusion in the ischaemic area, a decrease in
      the extent of infarction site and a decrease in mortality. TL administered within
      the initial hours after the onset of AMI leads to better results than when
      administered after several hours. Currently, TL is not limited by age. The
      patients who were given streptokinase (SK) or anistreplase (APSAC) prior to more
      than 4 days, if necessary, urokinase or alteplase (rt-PA) should be given. There
      are differences in the opinions as to the optimal selection of thrombolytic
      drugs. However, all currently used drugs lead to a significant decrease in
      mortality due to AMI. The preferential use of accelerated administration of rt-PA
      in contrast to SK is justified in younger patients with extensive AMI of the
      anterior wall, in whom the therapy has begun within 4 hours since its onset. The
      occurrence of severe bleeding indicates that TL should be halted and coagulation
      factors should be replaced by freshly frozen plasma or fibrinogen concentrate, if
      necessary, transfusion of full blood should take place. If the severe bleeding
      occurs shortly after the administration of SK, the persisting plasminaemia can be
      arranged by antifibrinolytic drugs. An improvement in TL results can be achieved
      by adjuvant antithrombotic therapy. At the same time, in addition to
      acetylsalicylic acid, the patient treated with rt-PA should be given heparin.
      Heparin administration is not necessary in patients treated with SK or APSAC.
      However, heparin is indicated in patients at risk due to systemic embolization in
      congestive heart disease, extensive infarction or atrial fibrillation. (Tab. 1,
      Ref. 28.)

PMID- 9919746
TI  - [Reperfusion arrhythmias].
AB  - Reperfusion arrhythmias originate as a consequence of the complex of cellular and
      humoral reactions accompanying the opening of coronary artery. As the primary
      cause of their generation are considered the chemically defined substances that
      are produced and accumulated in myocardium during reperfusion. The key role is
      ascribed to free oxygen radicals but of importance are also other substances such
      as calcium, thrombin, platelet activating factor, inositol triphosphate,
      angiotensin II and others. These chemical mediators of reperfusion arrhythmias
      operate as modulators of cellular electrophysiology causing the complex changes
      at the level of ion channels. It is supposed that in the genesis of reperfusion
      arrhythmias unlike ischemic arrhytmias operate nonreentrant mechanisms such as
      abnormal or enhanced automacy and triggered activity due to afterdepolarizations.
      As a typical reperfusion arrhythmia is considered an early (within 6 hours after
      start of thrombolysis), frequent (> 30 episodes/hour) and repetitive (occurring
      during > 3 consecutive hours) accelerated idioventricular rhythm (AIVR). AIVR
      with such characteristics has a high specificity and positive predictive accuracy
      but relative low sensitivity as a predictor of reperfusion. Thus, in occurrence
      of AIVR, recanalization of infarction-related coronary artery is very probable,
      but in absence of AIVR, reperfusion is still not excluded. The following
      arrhythmias are regarded also as markers of reperfusion: frequent premature
      ventricular complexes (> twofold increase in frequency within 90 minutes after
      the start of thrombolysis), a significant increase of episodes in nonsustained
      ventricular tachycardia, sinus bradycardia and probably also high-degree
      atrioventricular blocks. At present, there is no definite evidence, as to whether
      sustained ventricular tachycardia and especially ventricular fibrillation can be
      caused by reperfusion. Reperfusion arrhythmias are an important noninvasive
      marker of successful recanalization of infarction-related coronary artery.
      However, they are also a sign of reperfusion injury and a finding which may limit
      the favourable effect of reperfusion. In account of that, there is a very
      intensive search for pharmacologic interventions which could protect or attenuate
      the reperfusion injury and thereby also the genesis of reperfusion arrthythmias.
      Although promising results were obtained with many substances antagonizing the
      effects of mediators of reperfusion injury, there is no definite recommendation
      for their use under clinical conditions. However, the results from the latest
      clinical trials with ACE inhibitors are very promising. These trials render
      relative conclusive evidence, that ACE inhibitors could have a protective effect
      against reperfusion arrhythmias. (Ref. 89, Tab. 1.)

PMID- 9919747
TI  - [Supraventricular arrhythmias and disorders of atrioventricular and
      intraventricular conduction in patients with acute myocardial infarct].
AB  - In addition to ventricular arrhythmias, various forms of supraventricular
      arrhythmias (SVA) and atrioventricular (AV) and intraventricular (IV) conduction
      disturbances occur also in acute myocardial infarction (AMI). In the setting of
      AMI, SVA may be caused by relevant atrial ischemia or infarction. SVA complicate
      the course especially that of inferior, posterior and lateral AMI. SVA occur
      frequently also in the right ventricular myocardial infarction and in
      pericarditis. SVA appearing in the late phase of AMI are caused particularly by
      hemodynamic factors especially those of both left and right ventricular
      dysfunctions. Atrial dilatation and the increase of intraatrial pressure are also
      important factors in the genesis of SVA. The autonomous nervous system,
      electrolyte disturbances, acidosis and global hypoxia may operate as modulating
      factors in the development of SVA. AV conduction disturbances are significantly
      more frequent in patients with inferior than with anterior AMI. In inferior AMI,
      they are frequently caused by reflex parasympathetic activation. In the genesis
      of AV conduction disturbances, a significant role may be played also by the
      following mechanisms: ischemia or necrosis of AV node or AV junction and the
      negative dromotropic effect of adenosine and potassium which are released to a
      great extent during myocardial ischemia and reperfusion. A high-degree AV block
      complicating the course of inferior AMI has a significantly better prognosis than
      that occurring in the setting of anterior AMI. In inferior AMI, AV block is
      frequently reversible, whereas in anterior AMI, it is persistent and
      irreversible. Early AV conduction disturbances, appearing within 24 hours of AMI
      have a better prognosis than those occurring in the late phase of AMI. Bundle
      branch blocks (BBB) complicating the course of AMI are caused by occlusion of
      bundle-related coronary artery or by serious ischemia in its bed. BBB is
      frequently a marker of a multivessel disease. New BBB appearing in AMI especially
      the right bundle branch block is considered as an predictor for the development
      of a complete AV block. Frequent and repetitive SVA as well as serious AV and IV
      conduction disturbances are frequently associated with a significantly worse
      clinical course of AMI and with increased mortality, with that of especially
      hospital mortality. However, this is usually not caused by SVA or AV and IV
      conduction disturbances per se. The major cause of death in these patients are
      heart failure, cardiogenic shock and malignant ventricular arrhythmias due to
      larger AMI, significant reduction of left ventricular function and advanced
      coronary heart disease. Complex SVA as well as serious AV and IV conduction
      disturbances are usually considered as markers, but not as independent predictors
      for both increased hospital mortality and in some cases also for that of
      posthospital mortality. Their occurrence in AMI may help to identify the patients
      at great risk who require a very intensive treatment including aggressive
      management of extensive coronary heart disease. (Ref. 62.)

PMID- 9919748
TI  - [Invasive diagnosis, transcatheter and surgical treatment of acute coronary
      syndromes].
AB  - On the basis of long-term personal experiences and critical evaluation of the
      present literatury sources authors described the role of invasive diagnostic
      methods and transcathetral and cardiosurgical possibilities in the recognition
      and therapy of acute coronary syndromes. These techniques are, and in the
      forthcoming year shall be available only in specialized institutions. The paper
      describes the indication for these aggressive techniques as well as their
      limitations and complications. The goal of the presented article is to inform
      both the cardiological and frequently broad physicians' societies about the
      possibilities of diaventional cardiology and cardiosurgery which will be
      gradually more applied in the care of the patients with acute coronary syndromes.
      (Ref. 39, Tab. 2, Fig. 3.)

PMID- 9919749
TI  - [Secondary prevention in patients after a myocardial infarct].
AB  - The confirmation of ischaemic disease of the heart increases the probability of
      death due to cardiovascular causes to more than 80%. The overcoming of myocardial
      infarction increases, according to the past AHA data, the risk of the origin of a
      new coronary episode 5 or 7-fold. The necessity of decreasing this risk in the
      frame of secondary prevention is therefore very urgent. The first assumption of
      success in secondary prevention resides in optimal therapy in the acute phase of
      myocardial infarction. The thrombolytic therapy is accompanied by risks of re
      perfusion lesion implying from the increased production of free oxygen radicals,
      activation of leukocytes, intracellular calcium overload at a current deficit in
      potassium and magnesium, the defects of coronary microcirculation, increased
      sympathetic activities, general disturbances of energetic reserves in myocardium.
      Very significant is an early stratification of patients after MI to those
      indicated to intervention/in case that the mass of ischaemic myocardium exceeds
      20%, or if EF is below 40%, and to patients who regarding the low risk are
      manageable by conservative procedure. Both groups profit from the modification of
      classical risk factors (hypertension, smoking, hypercholesterolaemia). The values
      of cholesterol measured within the acute phase of myocardial infarction are not
      indicative, very often they are low. Finally, also in the later period with so
      called adequate values of the total cholesterol, the patient after overcoming IM
      is increasingly under threat. The aim of secondary prevention is to reduce the
      chief pathogen, namely LDL cholesterol below 2.6 mmol/l, the level of HDL
      cholesterol on the opposite should be above 1.0 mmol/l. It is necessary to re
      emphasize that the bioactive capacity is borne but by the oxidated form of LDL.
      Oxidative stress has a direct negative effect on vascular endothelium, and
      haemocoagulation potential, it participates in the metabolic X syndrome (insulin
      resistance, hyperinsulinaemia, defects in glucose tolerance,
      hypertriglyceridaemia, hypertension). (Ref. 41.)

PMID- 9919751
TI  - [Endothelial diseases and endothelium-protective agents].
AB  - Endothelial dysfunction plays the key role in the development of cardiovascular
      system disorders. Using certain markers it is possible to evaluate the
      endothelial function alterations and in this way to propose the disease
      prognosis. Recently the number of information concerning possible reversibility
      of these changes and the pharmacological intervention increases. Partial data
      about endothelium protective properties of ACE inhibitors, hypolipidemics,
      pentoxifyllin, Ca2+ channel blockers, lazaroids, glycosaminoglycanes exist. In
      experimental conditions it is possible to evoke endothelial dysfunction and
      evaluate the effects of these substances. Glycosaminoglycan sulodexide reduced
      endothelial losses at in vitro conditions of vessel perfusion on the model of
      endothelium damage by vasoconstrictive stimuli. Further evidence of these
      substances efficacy is required for the clinical evaluation of their endothelium
      protective properties. The research direction in this field will certainly
      provide such information concerning the endothelial function moderation which may
      be able to change the strategy of vascular diseases pharmacotherapy. (Tab. 5,
      Ref. 66.)

PMID- 9919750
TI  - [Functions and dysfunctions of the vascular endothelium].
AB  - Endothelium represents a large paracrine gland with an enormous reactive surface.
      By means of its numerous vasodilation and vasospastic factors it manages the
      basal and working tonus of vessels and thus also the regional flow and the access
      of target tissues to hormones and metabolic substrates. It manages also the
      proliferation and migration of myocytes of the vascular wall and thus its
      adaptation to overload. The dysfunctional states of endothelium are observed in
      arterial hypertensions, diabetes, dyslipoproteinaemia, and they grow with age.
      They are the first stage of atherothrombogenic processes. They manifest
      themselves by a decreased vasodilation reserve of the vascular wall to strain,
      insulin and many other stimuli. On the contrary, quite frequently they
      paradoxically react to physical strain, acetylcholine, histamine, ATP etc. by
      vascular spasms which can determine vasospastic and microvascular angina pectoris
      including spasms and occlusions of e.g. coronary arteries in sites of
      insignificant stenoses with the origin of infarctions. The damaged endothelium,
      so to explain, conceives these stimuli in accordance with the encoded programme
      as a stimulus to the protection from haemorrhage during stress (fight or flight)
      and develops "suicidal" defensive reaction against them which we are nowadays
      able to modulate by administration of ACE-inhibitors, beta-blockers,
      hypolipidaemic drugs, inhibitors of cyclooxygenase-1 (30-100 mg of aspirin), Ca
      antagonists and antioxidants including numerous non-pharmacological procedures.
      We can retard or halt the process of atherothrombogenesis and avoid or lower thus
      the number of sudden vascular ventricular as well as brain episodes, including
      the congestive heart failures, limb amputations and ischaemic damage of the
      brain. (Fig. 4, Ref. 70.)

PMID- 9919752
TI  - [Memory, awareness and learning in general anesthesia].
AB  - Enough information concerning memory and other cognitive functions in total
      anesthesia is available in the literature. Some basic theories about neuronal
      mechanisms of memory and consciousness are known. An attempt trying to bridge the
      gap between psychological and biologic levels is the usage of anesthetics in
      pharmacologic tests enabling the study of their influence on awareness and memory
      in humans. With the help of this approach it is possible to inquire into the
      psychological mechanisms and to demonstrate the influence of anesthetics on them.
      44 patients were included in the study, operated on in inhalation anesthesia. The
      effects of anesthesia on awareness, consciousness, learning and memory in our
      study sample were following: 1. No episode of awareness was observed during the
      study; 2. There was an improvement of the memory quotient (MQ) following total
      inhalation anesthesia (p < 0.05); 3. The pain threshold significantly decreased
      after anesthesia (p < 0.001); 4. There exists a learning mechanism in total
      anesthesia more efficient in the group of patients auditively learning pain
      related words (p < 0.05) comparing to the control group of patients auditively
      learning pain nonrelated words; 5. Statistical analysis of the number of
      remembered pain related words and pain nonrelated words revealed significantly
      higher number of words in the first group of pain related words (p < 0.001).
      (Tab. 3, fig. 6, Ref. 22.)

PMID- 9919753
TI  - [Atherogenic and anti-atherogenic plasma lipoproteins modulate secretion of
      prostanoids by endothelial cells in vitro].
AB  - The authors present the evidence of atherogenic properties of VLDL and LDL
      potentiation on the model of endothelial cells-human umbilical vein endothelial
      cells, by preferable stimulation of the endothelial cell to thromboxane A1
      production at in vitro conditions by atherogenic lipoproteins. The
      vasoconstrictive, thrombogenic and atherogenic effects of TXA2 are exerted on the
      vessel in this way. The ratio prostacycline/thromboxane, decisive for the
      maintenance of vascular homeostasis, is less than 1, this means the beneficial
      effect of prostacycline can not be applied. Protective, antiatherogenic effect of
      HDL and its subfractions HDL2 and HDL3/predominantly through their function in
      the reverse cholesterol transport from the periphery to the liver, antioxidative
      influence on LDL, as far as antiaggregation and fibrinolytic effects of HDL/is
      multiplied by the fact that HDL preferably stimulates the secretion of
      prostacycline by the endothelial cell. The ratio prostacycline/thromboxane A2 is
      higher than 1, that means beneficial vasodilative, antiaggregation and
      antiatherogenic effect of prostacycline on the vessel wall predominate.
      Quantitative evaluation of antiatherogenic effects of HDL subfractions (HDL2 and
      HDL3) revealed more significant antiatherogenic effect in HDL2 subfraction-in the
      sense of prostacycline secretion stimulation and exertion of its beneficial
      effects on the vessel. (Fig. 5, Ref. 33.)

PMID- 9919754
TI  - [Actions of drugs affecting the cough reflex].
AB  - BACKGROUND AND AIM: Authors evaluated the part of some receptor systems in the
      antitussive activity of drugs. METHOD: The cough was induced by mechanical
      stimulation of the airways. Unanesthetized cats were used in this study. RESULTS:
      They followed: 1. statistically highly significant decrease of cough parameters
      after administration the drugs influencing the different types of opiate
      receptors--tramadol, tilidine, pentazocine, codeine and butorphanol. Every of
      these drugs were administered in a dose 10 mg/kg b.w. intraperitoneally, 2. the
      antitussive activity of codeine was decreased by pretreatment with naloxone only
      in part, 3. selective antagonist 5-HT2 receptors ketanserine (1 mg/kg b.w.)
      decreased antitussive effect of codeine by 10% and effect of tramadol by 20%, 4.
      the ability of codeine to reduce the cough parameters was unchanged after
      pretreatment with haloperidol (0.1 mg/kg b.w.), 5. whereas the pretreatment with
      reserpine decreased the cough-suppressing effect of codeine, 6. the application
      of gabaergic agent gabalid leads to the highly significant decrease the cough
      parameters. Results of these experiments showed that gaba-ergic mechanism might
      be involved in the mechanism of action of narcotic antitussives agents, 7. we
      showed, that inhibition of glutaminergic synaptic transmissions afferent impulses
      from cough receptors with dextromethorphan leads to suppressing cough reflex in
      cats. CONCLUSIONS: Antitussive activity of agents is not only mediated by means
      of mi opiate receptors. The results suggest, that gabaergic, serotoninergic
      systems and activity of NMDA receptors play an important role in the mechanism of
      action of antitussive drugs. Decrease in levels of brain monoamines modifies the
      cough-depressant effect of codeine. (Fig. 7, Ref. 23.)

PMID- 9919756
TI  - [Analysis of inversion in intron 22 of the factor F VIII:C gene in patients with
      hemophilia A in the Slovak population].
AB  - Hemophilia A is the result of Factor F VIIIC (F8C) gene mutations. Predominating
      mutation is inversion, occurring in about 50% of patients with severe form of the
      disease. Inversion is the result of homologous recombination between gene A
      located on the 22. introne of the F8C gene and one of its telomeric copies
      located about 500 kb from 5'end of the factor F VIIIC gene. This study presents
      the results of this mutation screening in 84 nonrelated patients with hemophilia
      A. Inversion was identified in 22 (50%) of 44 patients with severe form and in 1
      (from 13) with moderate form of the disease. Distal type of inversion was more
      frequent (82.6%) than proximal one. The identification of iversions enabled
      direct DNA diagnosis in 50% of patients with severe form of the disease and will
      be successfully used in the prenatal diagnosis and carrier testing, mainly in
      families with sporadic occurrence of the disease. (Tab. 1, Fig. 2, Ref. 18.)

PMID- 9919758
TI  - [Health insurance].

PMID- 9919757
TI  - [Diagnosis of familial adenomatous polyposis based on DNA].
AB  - BACKGROUND: Familial adenomatous polyposis is an autosomal dominant precancerous
      condition, characterized by the appearance of hundreds to thousands of colorectal
      polyps. Mutation of the APC gene located on 5q21-22 plays the major role in its
      etiology. OBJECTIVE: Diagnoses and genetic prognosis of 7 persons of a family
      with previous case of FAP using combination of two molecular methods-heteroduplex
      and linkage analysis. METHODS: In heteroduplex analysis (HDA) the E-G region of
      the 15 exon of the APC gene was amplified using PCR. PCR products were then
      loaded on nondenaturating polyacrylamid gele and visualised by silver staining.
      In linkage analysis we used linkage between pathologic alele of the APC gene and
      MspI polymorphism. RESULTS: Using heteroduplex analysis an identical mutation in
      two persons in suspected region was detected and linkage analysis revealed that
      pathologic alele of APC gene in one person is linked to B2 alele of MspI
      polymorphism. For the second person the linkage analysis was not informative.
      CONCLUSIONS: Using these methods presymptomatic diagnostics of FAP, genetic
      prognosis and detection of persons at high risk have become available. Comparing
      to classical diagnostics these methods are quick, exact not embarrassing for the
      patient and it is not necessary to repeat them. (Fig. 3, Ref. 13.)

PMID- 9919759
TI  - Word analysis--a useful tool in learning the language of medicine in English.
AB  - Derivated medical terms can consist of a prefix, one or two word roots, a
      combining vowel, and a suffix in various combinations. To teach medical
      vocabulary means to teach the tools of word analysis that will enable
      understanding of complex terminology instead of memorising the whole medical
      dictionary. (Ref. 6.)

PMID- 9919755
TI  - [Acute intermittent porphyria].
AB  - Acute intermittent porphyria is an autosomal dominant condition caused by a
      genetic defect of the deaminase gene located on the 11. chromosome. Due to this
      defect only 50% of the normal enzyme quantity is produced. The disease becomes
      manifested only in the case of increased demands on given metabolic pathway
      resulting in porphobilinogen accumulation and storage in the organism. Clinical
      pattern involves abdominal, neurologic and psychiatric symptomatology. Laboratory
      diagnosis is based on the detection of delta-aminolevulinic acid,
      porphobilinogen, uroporphyrin and coproporphyrin in the urine. Between the
      attacks may only the detection of porphobilinogen deaminase in erythrocytes,
      leukocytes and skin fibroblasts be positive. The therapy is based on infusions of
      20% glucose solution and hydromineral imbalance correction. When neurologic
      symptoms occur it is necessary to administer hem-arginate intravenously. The case
      report presents almost textbook case of a young female patient suffering from the
      disease. (Ref. 7.)

PMID- 9919760
TI  - [Epidemiologic and microbiologic aspects of mycobacteriosis in Slovakia--M.
      xenopi].
AB  - The first mycobacterioses caused by M. xenopi in Slovakia were discovered in the
      year 1979. Gradually they became the most often occurring mycobacterioses caused
      by facultative pathogenic mycobacteria. The purpose of investigation is to
      describe epidemiological situation of diseases caused by M. xenopi in Slovakia
      and to confront it with the situation in chosen developed countries. The
      methodology of this paper is based upon surveillance of tuberculosis as applied
      on mycobacterioses. During the period of last 10 years 960 isolations of M.
      xenopi from 622 persons were registered in Slovakia. Pulmonary mycobacterioses
      caused by M. xenopi was discovered in 58 persons until the end of the year 1966,
      48 of them are men and 10 are women. The most often transmission factor is water
      in water supply mainly in city-habitation and hospital environment. The
      occurrence has endemic character. (Ref. 31.)

PMID- 9919761
TI  - [Morphology and diagnosis of the oral protozoans Trichomonas tenax and Entamoeba
      gingivalis using the Giemsa-Romanovsky stain].
AB  - In the microscopic diagnosis of Trichomonas tenax and Entamoeba gingivalis is the
      technically and time not demanding native preparation of a culture, in which both
      protozoans can be detected according to their typical motility, determining. In
      the permanent preparation of the culture stained according to Giemsa-Romanovsky,
      which has also documentary character, are all of the characteristic cell
      organelles stainable, enabling so their detection without their typical motility.
      Staining according to Giemsa-Romanovsky is technically simple and not time
      consuming, not very laborious, low cost and the coloration is permanent, that
      means optimal for the diagnostic of oral protozoans in permanent preparations.
      (Fig. 5, Ref. 4.)

PMID- 9919763
TI  - [Toxoplasma gondii].
AB  - The authors offered a general view on Toxoplasma gondii from the historical,
      taxonomic, biological and epidemiological point of view. They also studied the
      problems of pathogenesis, pathology, clinics, diagnosis, as well as therapy and
      prevention. (Tab. 1, Ref. 9)

PMID- 9919762
TI  - [Occurrence of gram-negative non-fermenting rods in hemocultures and their
      sensitivity to antimicrobial agents].
AB  - In the period from January 1993 to June 1996 were at the Department of
      Microbiology of the University Hospital in Olomouc 122 strains of Gram-negative
      nonfermentative rod-shaped bacteria isolated from haemocultures. The majority
      represented the group of 51 strains of the genus Acinetobacter (41.8%), complex
      A. calcoaceticus-baumannii (Acb complex). The second largest group were 21
      strains (17.2%) of Pseudomonas aeruginosa. These were followed by 17 strains
      (13.9%) of Stenotrophomonas maltophilia, 8 strains (6.6%) of non-Acb complex
      acinetobacters, 6 strains (4.9%) of Pseudomonas putida and 5 strains (4.1%) of
      Alcaligenes xylosoxidans. The remaining species were represented only by 1-2
      strains. In three isolations was the identification impossible. The majority of
      strains (24.6%) were from the Department of Haematology of the University
      Hospital in Olomouc. The most frequent diagnoses in patients with positive
      haemocultures were leukemias and lymphomas (24.6%). The most effective tested
      antimicrobial agents were ceftazidime (93.4% of sensitive strains) and ofloxacin
      (91.7%). From the total number of 80 strains detected using the equipment
      BacT/Alert 120, 22 (27.5%) were isolated repeatedly confirming their role in the
      etiology of bacteriemic or septic episodes. Because only one blood sample was
      obtained in 34 cases (58.6%) of the remaining 58 only once detected strains, it
      was impossible to confirm their etiologic role by repeated isolation. (Tab. 6,
      Ref. 22.)

PMID- 9919764
TI  - [Diagnosis and treatment of cystic echinococcosis].
AB  - New data are given on the life cycle of tapeworms of the genus Echinococcus,
      agents of a serious helmintozoonotic disease. The tapeworm Echinococcus
      granulosus, the agent of cystic echinococcosis, circulates also in Slovakia.
      Cystic echinococcosis most frequently affects the liver and a radical surgical
      treatment supplemented with the application of antiparasitics are the commonly
      used methods. The authors present the WHO proposal for classification of
      echinococcal cysts into 6 types, according to ultrasound imaging. They also
      report on a new technique known as PAIR (puncture--aspiration--injection-
      reaspiration), successfully used in many patients in endemic countries. They warn
      of a rapid distribution of the tapeworm E. multilocularis, the agent of alveolar
      echinococcosis, in central Europe. (Ref. 13.)

PMID- 9919765
TI  - [Juvenile hyaline fibromatosis].
AB  - BACKGROUND: Juvenile hyaline fibromatosis is a sporadic hereditary disease with
      autosomal recessive mode of inheritance, characterized by the presence of nodules
      and tumours in the skin and soft tissues and gingival hyperplasia. The majority
      of patients are growth retarded, suffer from joint disorders, contractures,
      osteolytic lesions and have a positive family history. The disease most
      frequently occurs in children, but may be diagnosed also in adults. Since 1873,
      when the disease was described by Murray, only a few cases were introduced in the
      literature. THE AIM AND THE BASIS OF THE STUDY: To present the clinical pattern
      of a patient diagnosed at the age of 28 and describe also the histopathological,
      immunohistological and electron-microscopic findings of excisions from the
      lesions. METHODS: The pathologist in cooperation with clinicians from several
      disciplines established the diagnosis on the basis of typical histopathological
      picture and additional immunohistological tests not yet introduced in the
      literature. RESULTS: Tumorous lesions contained hyaline structureless matrix
      often with chondroid or even osteoid metaplasia, calcium salts. The matrix
      contained numerous fibroblastoid-like cells with eosinophilic cytoplasm, oval
      nucleus and often pericytoplasmic halo. ELMI investigation revealed dilated
      cisternae of rough endoplasmic reticulum and hypertrophic Golgi apparatus.
      Sporadically were particles with calcium salts density detected.
      Immunohistochemical tests revealed the expression of vimentin, alfa1-antitrypsin
      and alfa1-antichymotripsin by the tumorous cells. CONCLUSION: The authors
      presented an extremely sporadic childhood disease in an adult. The results are in
      accordance with the data from the literature. Immunohistochemical picture of
      "cementicles" has not yet been introduced in the available literature. (Fig. 12,
      Ref. 25.)

PMID- 9919766
TI  - [DNA typing of class I HLA alleles].
AB  - The major histocompatibility complex (MHC) in man, the HLA-complex, is for its
      marked significance in the regulation of immune system reactions and for its
      important role in clinical medicine the object of incessant interest for further
      studies. There is also a constant search for new methods of HLA typing. HLA
      antigens have been traditionally detected by serological and cellular methods.
      Recently HLA typing methods based on DNA typing utilising polymerase chain
      reaction (PCR) are being introduced. PCR-SSO (sequence-specific oligonucleotide)
      and PCR-SSP (sequence-specific primers) methods are most frequently used for
      routine typing of HLA class I alleles. We present technical details of the PCR
      SSP method, recently introduced at our department and a short review of other
      techniques. (Fig. 1, Ref. 34.)

PMID- 9919767
TI  - [Frequency of loci of HLA-DRB1* and -DQB1* alleles in the Slovak population].
AB  - Results on HLA-DRB1* and HLA-DQB1* allele frequencies in the Slovak population by
      PCR-SSP method are presented. HLA-DRB1* alleles were determined in 130 and HLA
      DQB1* alleles in 143 healthy unrelated individuals. The highest frequency was
      observed for the alleles HLA-DRB1*1101-13 (0.203), HLA-DRB1*0701 (0.142), HLA
      DQB1*0301 (0.244), and HLA-DQB1*0201 (0.209). The least frequent alleles were HLA
      DRB1*1402-6-9, HLA-DRB1*0901 (both 0.0038), HLA-DQB1*0401 (0.007), and HLA
      DQB1*0601 (0.0035). The results obtained by DNA-typing were compared with those
      calculated from the serological study. No statistically significant differencies
      were found. The allele frequencies obtained in our study were also compared with
      those of the Czech and Austrian populations. No statistically significant
      differencies were observed. (Fig. 2, Tab. 3, Ref. 13.)

PMID- 9919768
TI  - [Spinal root compression and results of treatment of discogenic cauda equina
      syndrome].
AB  - Several experimental and clinical studies suggest an important role of the
      quality and quantity of the material compressing the lumbosacral spinal cord
      radices in the development of cauda equina syndrome. These facts inspired the
      author to find out if the repair of neurological functions depends also on these
      factors. Clinical investigations of 81 persons (30 women and 51 men) were
      performed at minimum time of two years after the operation of the cauda equina
      discogenic syndrome. Mathematical analysis of the acquired data (chi-quadrate)
      revealed that so-called soft compression of neural structures (intervertebral
      disc hernia, sequester liber) negatively influenced the restoration of lower
      extremities motor functions (p = 0.01), sexual functions in men (p = 0.05) and
      radicular pain persistence (p = 0.01). On the other hand, the so-called hard
      compression (spondylosis deformans and protrusion of intervertebral disc)
      negatively influenced the restoration of sensitive innervation (p = 0.01) and
      voluntary control of urinary bladder emptying (p = 0.01). (Tab. 7, Ref. 24.)

PMID- 9919769
TI  - [Quantification of pericentral NADPH-diaphorase neurons in the spinal cord of
      rabbits].
AB  - BACKGROUND: The freely diffusible radical nitric oxide is generated by nitric
      oxide synthase, and is bioregulatory molecule that functions as a major
      neurotransmitter. Constitutive nitric oxide synthase exhibits NADPH-diaphorase
      activity that can be demonstrated histochemically. OBJECTIVE: The purpose of the
      present investigation was to characterize and determine number of NADPH
      diaphorase positive neurons around the central canal in all segments of the
      rabbit spinal cord. METHODS: Rabbits Chinchilla were used in this experiment.
      After intracardiac perfusion the spinal cords were removed, cut into slices and
      histochemical analysis of NADPH-diaphorase activity was performed. Sections were
      evaluated by using light microscope. RESULTS: NADPH-diaphorase positive
      pericentral neurons were present in cervical, thoracic, lumbar; sacral and
      coccygeal segments. They differed in the shape of their bodies and in length and
      branching of their processes. The main differentiation was observed in their
      number depending on the place of localisation. The highest number of these NADPH
      diaphorase positive neurons was in sacral part (6 in average), the lowest one was
      noticeable in thoracic spinal cord (1-2 in average). CONCLUSION: Thus, our study
      suggests that pericentral neurons of the rabbit spinal cord which are capable of
      synthesizing nitric oxide, differs in number amount depending on the place of
      their localization in each spinal cord segments. (Tab. 2, Fig. 9, Ref. 21.)

PMID- 9919770
TI  - Construction of a quantitative PCR system to determine expression of tumor
      associated antigen.
AB  - Cancer immunotherapy is a strategy for cancer treatment by induction of anti
      tumor responses. The identification of candidate tumor associated antigens (TAA)
      suggested their potential use as immunogens for vaccination studies.
      Quantification of a TAA expression by cancerous cells is an important factor in
      determination of induced immune response efficiency against tumors and thus
      enables us to devise optimal immunotherapy protocol to cure cancer. The
      quantitative polymerase chain reaction (PCR) enables us to compare the TAA
      expression in highly metastatic tumor clones with that in less metastatic ones
      and in normal cells. It allows us to gain more insight into genome rearrangements
      that occur in malignant transformation as well as broaden our knowledge about
      tumor cell gene expression regulation. One of the peptides isolated previously in
      our lab from a murine lung carcinoma is the mutated Connexin 37 (cx37), a gap
      junction protein. Research is underway to determine the expression level of the
      TAA in various Lewis lung carcinoma cells. This evaluation is achieved by means
      of quantitative PCR. A quantitative PCR experiment includes preparation of a
      control template, which is added in known amounts together with the target
      template in a series of amplification reactions. The control template uses the
      same primers as the target sequence, yet their PCR products differ in size so as
      to be distinguishable. Two methods were used to produce this control template.
      The first one included specific deletion of a sequence of approximately 100 bp
      that lay between the two primers, insertion of the new template into a plasmid
      vector, transformation of competent bacteria, detection of transformed bacterial
      colonies and isolation of the plasmid DNA in a large quantity. The non-mutated,
      deleted Connexin 37 cDNA was also isolated from bacteria and used for another
      experiment aimed at producing deleted, mutated Connexin 37 cDNA by means of
      primer mutagenesis. (Fig. 5, Ref 8.)

PMID- 9919771
TI  - [Preparation for heart transplantation in Slovakia 1994-1997].
AB  - The authors present the process of introduction heart transplant programme in the
      years 1994-1997 in Slovakia. A short historical review about heart
      transplantation is given in the article. Fundamental requirements for heart
      transplantation realization, activities of Working group "Heart transplantation",
      methods of follow-up of patients after heart transplantation and selection of
      candidates for transplantation, are discussed. The authors also deal with
      surgical and anaesthesiological prerequisites for this programme realization. In
      conclusion they claim that the requirements for regular programme of heart
      transplantation are accomplished. (Tab. 2, Fig. 3, Ref. 21.)

PMID- 9919772
TI  - [Hyperlipoproteinemia in patients after heart transplantation].
AB  - Hyperlipidaemia is one of the most frequent metabolic disorders after heart
      transplantation (HTx). The significance of hyperlipidaemia is stressed mainly in
      relation to graft vascular disease (GVD) which is the leading cause of death more
      than one year after transplantation. Recently the evidence on the role of
      hyperlipidaemia (HLP) in the pathogenesis of GVD is growing. Total cholesterol
      (TC), triglycerides (TAG) HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C)
      were analysed cross-sectionally in 35 patients (30 males), aged 20-64 (median 40)
      years, more than one year after HTx. In 25 patients HTx was performed because of
      dilated cardiomyopathy (D-KMP), in 10 because of coronary artery disease (CAD).
      TC more than 5.6 mmol/l was detected in 29 (83%), TAG > 2.3 mmol/l in 15 (43%),
      LDL-C >3.6 mmol/l in 28 (80%) and HDL-C < 1.4 mmol/l in 25 (75%) of patients.
      There were no statistically significant differences in evaluated parameters found
      between the groups of patients operated on because of CAD and D-CMP, with and
      without glucose tolerance disorder and groups treated with higher (> 5 mg/D) and
      lower (.5 mg/D) dose of prednisone. Significant linear correlation of body mass
      index (BMI) and TAG or BMI and HDL/C resp. was confirmed. Pathogenesis of HLP
      after HTx is complex. Except of obesity, no unambiguous evidence of the role of
      glucose tolerance disorder or prednisone dose in immunosuppressive treatment were
      found. (Tab. 2, Fig. 3, Ref. 21.)

PMID- 9919774
TI  - [Psychological aspects of heart transplantation].
AB  - The aim of our work was to stress the role of some psychologic and psychosocial
      factors participating significantly in the emotional experiencing, in the period
      before and after heart transplantation, respectively. The uniqueness of the
      patients personality is emphasized with the aim to sensitively and competently
      help them to improve their experiencing and quality of life. The author tried to
      acquaint the general health public with various approaches to this very complex
      problem. Main interest was focused on the predictors of successful heart
      transplantation, the criteria and contraindications of HTx, the waiting period
      for transplantation. The problems of depression, anxiety, denial, noncompliance
      and the selection of appropriate coping mechanisms--which are the most frequently
      occurring psychological factors directly influencing the behaviour and
      experiencing of the patient--HTx candidate were presented. In conclusion specific
      problems of HTx (the approach to the patient when informing him about the
      necessity of HTx and the relations of patients with the donor family) are
      discussed. (Tab. 2, Fig. 4, Ref. 34.)

PMID- 9919773
TI  - [Diagnosis and therapy of acute rejection in patients after orthotopic heart
      transplantation].
AB  - OBJECTIVE: In organ allotransplantation represents a serious problem acute
      rejection, which is the reaction of recipient organism aimed to reject the
      transplanted organ. AIM: To obtain experience in the field of routine long term
      are of patients after heart transplantation living in Slovakia. METHOD: 33
      patients after orthotopic heart transplantation (HTx) were included in our long
      term care by the 1. June 1996. According to the accepted protocol we make the
      whole set of examinations is performed. This includes endomyocardial biopsy which
      is the only reliable method for the detection of rejection and also the criterion
      of sufficiency of immunosuppressive therapy. RESULTS: Acute rejection was
      revealed in 14 (43%) patients. CONCLUSIONS: Tactics of therapy and the length of
      the interval to subsequent biopsy were determined according to the histological
      findings of preceding biopsy, the clinical status and the combination of
      immunosuppression therapy. (Tab. 2, Ref. 13.)

PMID- 9919775
TI  - [Congenital developmental defects of the cardiovascular system from the aspect of
      genetic factors and dysmorphogenesis].
AB  - Congenital defects of cardiovascular system have marked impact on the morbidity,
      invalidization and mortality of human population. Genetic factors are the most
      important factors in their etiology. The authors analyze the role of genetic
      factors and some problems of cardiovascular dysmorphogenesis important for
      evaluation of the reasons and risk of repeated congenital heart diseases family
      occurrence using clinical data and professional literature. (Tab. 7, Ref. 19.)

PMID- 9919776
TI  - Management of a cracked Acrysof intraocular lens during implantation. Case
      report.
AB  - The importance of a sufficiently large incision during soft intraocular lens
      (IOL) implantation is illustrated and highlighted by a single case study. In our
      patient, insufficient enlargement of the incision caused a crack in the optic of
      the Acrysof IOL. The IOL could, however, be left in place because of its
      excellent biocompatibility. Different management options are discussed.

PMID- 9919777
TI  - Multiple evanescent white dot syndrome.
AB  - The indocyanine green angiographic appearance in the Multiple Evanescent White
      Dot Syndrome is described in a young female patient, presenting with bilateral
      involvement. Multiple hypofluorescent dots in the posterior pole of the right
      eye, and a hypofluorescent peripapillary ring in both eyes were the
      characteristic findings at initial examination. Six weeks later, there was only a
      small, dense, dark ring around both optic nerves. CONCLUSION: The ICG angiography
      suggests a much more extensive choroidal involvement in MEWDS than is indicated
      by functional evaluation. The hypofluorescence around the optic disc could be
      related to the persistence of an enlarged blind spot.

PMID- 9919778
TI  - Retrospective study on the evolution of visual acuity after external beam
      radiotherapy (20 Gy, 2 Gy fractions) for subfoveal choroidal neovascular
      membranes in ARMD.
AB  - This is a retrospective study of 104 patients with a total follow-up between 12
      and 48 months (mean follow-up of 24 months), in which the effect of External Beam
      Radiotherapy with a total dose of 20 Gy (2 Gy fractions) on the visual acuity of
      eyes affected by subfoveal choroidal neovascularization is evaluated. The
      evolution of the visual acuity of the irradiated eyes is compared with the
      evolution of the visual acuity of their fellow eyes which were also affected by
      choroidal neovascularization but were not treated or treated by laser
      photocoagulation. This study suggests that the effect of radiotherapy, with a
      total dose of 20 Gy, on the visual acuity of eyes affected by subfoveal choroidal
      neovascularization, seems to be not better than the natural course of choroidal
      neovascularization or the evolution after laser therapy.

PMID- 9919779
TI  - Conventional retinal detachment surgery: technique, complications and results.
AB  - A uniform conventional technique, modified by Dr. Zivojnovic, was performed on
      104 consecutive patients with rhegmatogenous retinal detachments including
      pseudophakic eyes (23.1%) and cases with preoperative proliferative
      vitreoretinopathy (PVR) A-C2 (21.2%). A prospective study of 59 variables in 104
      cases shows the risk factors influencing the results after a minimum follow-up
      (F.U.) according to multivariate analysis: preoperative detached macula, vitreous
      loss during previous cataract surgery and duration of detachment. The anatomic
      (94.2% reattachment after external surgery) and functional results (69.2% V.A. >
      or = 0.5) are discussed as well as the complications.

PMID- 9919780
TI  - Costsaving in the operating room: the Procedure Pack.
AB  - The concept of the Procedure Pack is very relevant in this era of managed care.
      By collecting more items in one pack, the hidden costs will be reduced and the
      pack will become relatively cheaper than the sum of every item. This paper
      compares the price of the Procedure Pack with the price of the separate items
      used for routine phaco-emulsification. The Procedure Pack is 2% more expensive,
      but the benefits by reducing the hidden costs are substantial and will be
      analyzed.

PMID- 9919781
TI  - [Interest in the Heidelberg Retinal Flowmeter for measuring the retinal and
      papillary blood flow].
AB  - The Heidelberg Retina Flowmeter is a combination of Doppler flowmetry and laser
      scanning technology. It is new non-invasive method performing a high definition
      topography of perfused microvessels of the retina and optic nerve head with
      simultaneous evaluation of blood flow. Recent studies prove significant decrease
      of optic nerve head blood flow and juxtapapillary blood flow in primary open
      angle glaucoma.

PMID- 9919782
TI  - A large field Panel D-15 test for low vision patients.
AB  - A large surface Panel D-15 Test, specially designed for low vision patients, is
      presented. The value of the test is compared to the one of other standard colour
      vision tests in such patients.

PMID- 9919783
TI  - Diode laser cyclophotocoagulation in refractory glaucoma.
AB  - A retrospective analysis was made of the first 19 eyes of 19 patients with
      intractable glaucoma treated with contact diode cyclophotocoagulation. We
      assessed intraocular pressure (IOP) and number of glaucoma medications. The mean
      follow-up was 4 months (range 1 to 11 months). Mean IOP's decreased from 31.7 +/-
      14.6 pre-diode treatment to 23.7 +/- 16.9 mmHg at the last follow-up visit after
      treatment (p = 0.02). The mean number of medications required decreased from 1.9
      before to 1.3 after treatment (p = 0.03). The study suggests that diode
      cyclophotocoagulation is an effective and safe procedure in eyes with refractory
      glaucoma.

PMID- 9919784
TI  - [Reasons for return of patients for consultation after prescription for
      corrective glasses].
AB  - PURPOSE: To determine the frequency and causes of patients' complaints when they
      return visit less than one year after refraction. METHODS: Among all the patients
      who received a prescription of corrective glasses from January to December 1996,
      we include in the study those who returned less than one year after the
      refraction because they were dissatisfied with their spectacles. In order to
      determine the cause of their complaints, the patients were evaluated
      ophthalmologically and, depending on the complaints, an oto-rhino-laryngologic,
      dental, cardiovascular or neuro-psychiatric evaluation was made. RESULTS: During
      this period, 432 patients underwent refraction and had a prescription of
      corrective glasses. Of these, only 12 (2.8%) came back to consult. A cause could
      be found in 11 patients: error by opticians (3 patients), intolerance to bifocals
      (1 patient) and to cylindric lenses (1 patient), sudden onset of hyperopia
      associated with diabetes mellitus (1 patient), increase of refraction associated
      with progressive myopia (2 patients), fronto-maxillary sinusitis (1 patient),
      arterial hypertension (1 patient) and cataract (1 patient). CONCLUSION: Patients
      who received corrective glasses and return a short item after the refraction with
      complaints about their spectacles must be reevaluated ophthalmologically. If any
      cause can't be found, the evaluation should be extended to oto-rhino
      laryngologic, dental, cardiovascular, neuro-psychiatric or other examination
      depending on complaints.

PMID- 9919785
TI  - Is combined phacoemulsification and trabeculectomy as effective as trabeculectomy
      alone?
AB  - We reviewed the charts of 60 consecutive patients with open-angle glaucoma who
      underwent a trabeculectomy (T) or a single-site combined glaucoma and cataract
      procedure (phaco-trabeculectomy = PT) to compare the pressure lowering effect of
      both techniques. The pressure lowering effect after 12 months was significant in
      both groups: 11.44 +/- 5.94 mm Hg in the T-group and 5.00 +/- 4.51 mm Hg in the
      PT-group (p < 0.001). The pressure levels one year postoperatively were
      significantly lower in the T-group compared to the PT-group: 11.08 +/- 2.80 mm Hg
      versus 15.04 +/- 2.40 mm Hg (p < 0.001). Our results suggest that the combined
      procedure, although proven to be effective in lowering the intraocular pressure,
      is less effective than trabeculectomy alone.

PMID- 9919786
TI  - Chronic uveitis in Kinshasa (D R Congo).
AB  - PURPOSE: To determine frequencies of different types of chronic uveitis and the
      possible associated conditions. METHODS: In the retrospective study a review is
      made of all 336 consecutive patients with chronic uveitis seen during 1983
      through 1993. All patients were evaluated ophthalmologically and most of them
      medically. Traumatic uveitis was excluded from this study. RESULTS: There were
      171 (51%) males and 165 (49%) females. Of 336 patients with chronic uveitis, 194
      (58%) had anterior uveitis, 76 (23%) had isolated posterior uveitis, 38 (11%) had
      panuveitis and 28 (8%) intermediate uveitis. Associated conditions were found in
      151 (46%) of 336 patients. AIDS, Herpes Zoster Ophthalmicus, toxoplasmosis,
      tuberculosis, rheumatoid arthritis and onchocerciasis were the most common
      associated disease respectively in 12.5%, 6.4%, 6%, 6%, 6% and 4% of cases.
      CONCLUSION: The findings of this study were different from those of other studies
      published in Europe and the United States.

PMID- 9919787
TI  - [Bioactivity and effect of a mixture of pilocarpine and lysine on the pupil and
      intraocular pressure in rabbits].
AB  - Based on experiments with rabbit eyes (strain New Zealand white) the authors
      submit evidence that the metabolite which is formed as a result of interaction of
      2% pilocarpine and L-lysine 2 HCl.2H2O has a significantly greater and more rapid
      effect on the development of miosis than 2% pilocarpine alone. The amino acid
      lysine does not have a miotic effect. The authors explain the bioactivity of the
      new metabolite, its effect during the development of miosis and reduction of
      intraocular pressure. They emphasize a greater and more rapid bioactivity of the
      new metabolite as compared with pilocarpine. These results provide evidence that
      during treatment of primary glaucoma it is important to consider not only the
      effect on reduction of intraocular pressure but also physiological processes
      which develop in tissue structures after administration of different
      chemotherapeutic agents.

PMID- 9919788
TI  - [Treatment of internal carotid artery occlusion and the ocular ischemic
      syndrome].
AB  - The picture of severe ocular ischemic syndrome (OIS) drew attention to and
      investigations (sonography and carotid angiography) showed extensive
      atherosclerotic damage of vessels on more levels by a 46 year old patient with
      ischemic oculopathy, venous stasis retinopathy and neurological difficulties. The
      successful desobliteration of a. carotis interna adjusted the neurological
      difficulties of the patient and stabilized visual functions.

PMID- 9919789
TI  - [Trabeculectomy with releasable sutures and corneal topography].
AB  - We are interested in the influence of trabeculectomy (TE) with releasable sutures
      to corneal curvature in the early postoperative period. 35 eyes of 31 patients
      were followed after operation. Corneal topography was made on the Topograph
      Opticon 2000 one day before, 1st day, 1st week, 1st month and during 6-12 months
      after operation. Astigmatism after operations was the highest on 1st day +3.7 D,
      which means elevation of about +2.8 D. During 1st month postoperative astigmatism
      was decreased by about 2.0 D, it is about +0.8 D more than before operation.
      During 6-12 months after operation temporary astigmatism nearly disappears, it
      only makes +0.25 D. The axis of astigmatism was without larger alterations. Small
      temporary changes were seen according to the place of TE. Temporary astigmatism
      was observed immediately after the extraction of the releasable sutures.
      Astigmatism after operation was influenced by the rate of filtration during the
      short postoperative time and also after extraction of the releasable suture.

PMID- 9919790
TI  - [Contrast sensitivity in glaucoma and ocular hypertension].
AB  - It is known that contrast sensitivity declines with advancinG age and during
      different ophthalmological diseases. The authors examined 263 eyes of 141
      patients with different types of glaucoma and 213 eyes of 107 patients with
      ocular hypertension. The patients were divided into two groups by age: A = under
      60 years (mean 53.2 in glaucoma, 51.1 in OH) and B = 60 years and above (mean
      67.5 in glaucoma and 65.6 in OH). For examination of contrast sensitivity the
      authors used a VCTS 6500 board from a 3 m distance, the visual field was examined
      by means of Goldman's kinetic perimeter or a static Optifield II perimeter and
      the discs of the optic nerve were examined biomicroscopically or a photograph of
      the disc was taken. Impaired contrast sensitivity was found in group A in 71.7%
      of glaucoma patients and in 61.6% in ocular hypertension. In group B in 81.7%
      glaucoma patients and in 75.1% of patients with ocular hypertension. The authors
      also proved an association between the decline of contrast sensitivity and
      impairment of the perimeter and enlargement of the glaucoma excavation of the
      optic disc. The authors recommend examination of the contrast sensitivity as a
      supplementary method for screening and observation of ocular hypertension and
      glaucoma.

PMID- 9919791
TI  - [Endonasal endoscopic dacryocystorhinostomy].
AB  - Contemporary advances in endoscopic surgery of the paranasal sinuses make it
      possible to identify and open the lacrimal system via the nasal sinus. The
      authors describe four cases of chronic dacryocystitis with obstruction of the
      nasolacrimal duct in three women and one man aged 22 to 56 years. In all four
      patients the lacrimal sac was opened endoscopically by the endonasal route and
      safeguarded by drainage. In the discussion the authors deal with contemporary
      views on this problem.

PMID- 9919792
TI  - [Endoscopic endonasal dacryocystorhinostomy: indications, technique and results].
AB  - From 1996 till August 1998 the authors made 24 EDCRS in 23 patients aged 35 to 80
      years, incl. 6 men and 17 women. All patients reported epiphora, in 19 cases a
      mucous purulent secretion from the lacrimal pathways was present and 9 had a
      history of phlegmon in the area of the lacrimal sac. Irrigation of the lacrimal
      pathways revealed occlusion which was confirmed also on dacryocystography. The
      cause of occlusion was in four instances iatrogenic (rhinosurgical operation), in
      another two post-traumatic and in six there were pathological findings in the
      nasal cavity. In two instances the authors detected a dacryolith and in 10
      idiopathic stenosis was found. The operation was performed under general
      anaesthesia, using an endoscopic endonasal approach, without permanent or serious
      complications. On operation in 15 instances postsaccal stenosis was detected, in
      7 instances intrasaccal stenosis and in two patients a dacryolith was present. A
      concurrent mild presaccal stenosis was present in three patients and was treated
      by insertion of a catheter into the lacrimal pathways for a period of several
      weeks (except these situations the authors do not indicate its use). After 24
      EDCRS epiphora persists only in one patient (with a presaccal component of
      stenosis), in the remaining patients epiphora is no longer present and irrigation
      of the lacrimal pathways is free. Minor traumatization without injury of the
      medial palpebral ligament and normal function of the lacrimal pump are basic
      advantages of the endonasal approach. The majority of authors report patency of
      the lacrimal pathways which is achieved by the method of EDCRS in 83-86% of
      patients. The authors results are similar and justify the recommendation to
      consider EDCRS as the method of choice in the surgical treatment of intrasaccal
      and postsaccal stenoses of the lacrimal pathways.

PMID- 9919793
TI  - [Scintigraphy of the lacrimal ducts].
AB  - Scintigraphy of the lacrimal pathways is an examination method which informs us
      on the function of the efferent lacrimal system. The authors made bilateral
      scintigraphic examinations in 32 patients with obstruction or stenosis of the
      lacrimal pathways, 22 times they made concurrent contrast examinations of the
      lacrimal pathways. In seven suprasaccal and 5 saccal obstructions and stenoses
      they did not find penetration of activity from the conjunctival sac into the
      lacrimal pathways. In 16 subsaccal obstructions, 12 times penetration of activity
      into the lacrimal sac was found. In five patients with a partly preserved patency
      of the lacrimal pathways three times activity was detected in the lacrimal sac
      and in one instance slow penetration of activity into the nasal cavity. In
      complete obstructions and severe stenoses scintigraphy does not provide, as
      compared with conclusions of other examinations (fluorescein tests, irrigation,
      probing, contrast dacryocystography) new information on the type of obstruction.
      The method is useful in particular in conditions with a preserved patency of the
      lacrimal pathways, in examinations of very mild stenoses, intermittent
      lacrimation and doubtful cases. Scintigraphy of the lacrimal pathways is a
      supplementary method which must be evaluated in the context with other methods,
      in particular methods which provide information on the anatomy of the lacrimal
      system (dacryography).

PMID- 9919795
TI  - [Central serous chorioretinopathy--a new model of etiopathogenesis].

PMID- 9919794
TI  - [Central serous chorioretinopathy--treatment with beta blockers].
AB  - The authors present an account on their first experience with treatment of
      central serous chorioretinopathy (CSCHR) by beta-blocking agents. In 21 patients
      with CSCHR Trimepranol (metipranololum) a beta non-selective blocker, 2 x 10
      mg/day for two to three months was used. In 30 patients with CSCHR Vasocardin
      (Metoprololi tartas) was used i.e. a beta-1 selective blocking agent, 2 x 50
      mg/day for two to three months. In all patients remission of the disease
      occurred, on average 4.5 to 4.8 weeks after the onset of treatment. During
      treatment of CSCHR by beta-blocking agents no significant difference was found in
      the action of beta selective and non-selective blockers regardless of the
      duration of the disease before onset of treatment and the number of relapses.

PMID- 9919796
TI  - [Ocular complications in AIDS].

PMID- 9919797
TI  - Impediments in the treatment of schizophrenic patients.
AB  - Treatment for schizophrenic patients used to entail long hospitalization,
      including individual psychotherapy and sociotherapy, and ideally involved
      significant others, culminating in rehabilitation or continuation of education
      and follow-up treatment. Under such regimens available mostly in the private
      sector, one third of patients became well and another third recovered
      sufficiently to function in the community. There has always been a cohort of
      between 25% and 33% who failed to recover and who usually became chronic patients
      in governmental facilities. Comprehensive in-patient programs have virtually
      disappeared in the United States. This paper will present factors involved in
      this change and the ensuing deficiencies in care. These impediments will be
      considered under eight subheadings.

PMID- 9919798
TI  - Learning from mental illness, past and present.

PMID- 9919799
TI  - A special report on the National Congress on the Future of Medical Practice and
      Practice Management.

PMID- 9919800
TI  - Further thoughts on a sustainable medicine.

PMID- 9919801
TI  - Suicide is a private affair.

PMID- 9919802
TI  - In response to "The dream that never was: the rise and fall of socialized
      medicine in the United States of America".

PMID- 9919803
TI  - Need for solidarity.

PMID- 9919804
TI  - Transplantation immunology--the role of human leucocyte antigen in
      allorecognition.

PMID- 9919805
TI  - Infections in solid organ transplant recipients.

PMID- 9919806
TI  - Chronic allograft nephropathy: the inevitable outcome of renal transplantation?

PMID- 9919807
TI  - Pathology of the liver allograft.

PMID- 9919808
TI  - Bone-marrow and blood stem-cell transplantation.

PMID- 9919809
TI  - Pathology of heart transplant.

PMID- 9919810
TI  - Pathology of pulmonary transplantation.

PMID- 9919811
TI  - Transplantation in the central nervous system.

PMID- 9919812
TI  - [Factors affecting Neisseria meningitidis and Neisseria lactamica carrier state].
AB  - Invasive meningococcal diseases have become in the Czech Republic since 1993 a
      serious epidemiological and clinical problem due to a clonus which was not
      present previously: Neisseria meningitidis C:2a:P1.2,P1.5, ET-15/37. In 1996 a
      trial was conducted focused on the problem how this altered epidemiological and
      clinical situation is reflected in carriership of Neisseria meningitidis and
      Neisseria lactamica in the healthy population. Two age groups were followed up
      which were most severely affected by the new clonus of the meningococcus: 15-19
      years (410 subjects) and 1-4 years (116 subjects). The trial was implemented in
      Olomouc where in 1993 the new epidemiological situation of the incidence of the
      invasive meningococcal disease was so serious that targeted vaccination was
      introduced. Of 116 children in the age group from 1-4 years in none Neisseria
      meningitidis was detected, in 9 Neisseria lactamica was found (7.7%). On repeated
      examination of children with a positive cultivation of Neisseria lactamica after
      two weeks in none Neisseria meningitidis nor Neisseria lactamica were found. Of
      410 subjects in the age group from 15-19 years in none Neisseria lactamica was
      detected and in 35 Neisseria meningitidis (8.5%). Examinations were repeated
      after two weeks in 33 carriers: in 31 Neisseria meningitidis was again
      cultivated. Analysis of factors influencing carriership revealed in Neisseria
      lactamica two factors in young children which significantly promote this
      carriership: cold and close contact/kissing. A risk factor at the limit of
      significance are frequent respiratory diseases. In the carriership of Neisseria
      meningitidis in 15-19 year-old subjects six factors were revealed which promote
      carriership. A significant risk factor is close contact/kissing, the existence of
      partnership, participation in activities of the "disco" type, living in a town,
      flats in the centre of the town. Effort is a risk factor at the limit of
      significance.

PMID- 9919813
TI  - [Candida krusei (Castellani) Berkhout--a potential pathogen with growing
      importance].
AB  - The authors collect information on the biological properties, ecology and
      pathogenicity of Candida krusei. They give a list of forms of diseases caused by
      this yeast and a profile of its sensitivity to antimycotics. They point out the
      difference between C. krusei and species of C. albicans and analyze the factors
      enabling its propagation. In their opinion, the resistance of this yeast to
      fluconazole is the main cause of the increased number of colonizations and
      infections produced by C. krusei. The population of C. krusei resistant to
      fluconazole is selected from other, sensitive species of the genus Candida
      primarily in hospitalized patients. Though there is no consensus of opinion at
      present on the influence of fluconazole on the yeast spectrum, the authors
      suppose this systemic antimycotic plays a distinct role in the growing importance
      of C. krusei.

PMID- 9919814
TI  - [Specificity of serologic diagnostic tests for legionellosis].
AB  - Immune rabbit sera and sera of patients with legionellosis, leptospirosis, Q
      fever and antibodies against Borrelia burgdorferi were examined in cross
      reactions. In currently used serological tests, indirect immunofluorescence and
      the microagglutination test no antibodies were detected which could cause
      difficulties in the interpretation of results in the diagnosis of legionellosis.
      In one patient a mixed infection with Q fever and legionellosis was found.

PMID- 9919815
TI  - [Long-term monitoring of Neisseria meningitidis carrier state in the nasopharynx
      and seroprevalence of specific antibodies in immunized and non-immunized
      persons].
AB  - Long-term (three-month and one-year) follow-up of nasopharyngeal carriers of
      Neisseria meningitidis with a frequency of sample collection of once a week and
      once a month resp. in the healthy population with a mean age of 43 years revealed
      a 4.8% positivity (2 of 42 subjects). Carriership of the same phenotype and ET
      genotype of the N. meningitidis group 29E was stable in one subject, while the
      other long-term carrier of N. meningitidis group B has changes of the phenotype
      as well as ET-genotype during the follow-up period. Double (after a 3-month
      interval) verification of the seroprevalence of specific antimeningococcal
      antibodies revealed in a group of immunized subjects (vaccine A and C) a
      considerable degree of anti A immunity. Anti A-seropositivity in subjects
      immunized within a three-year interval since vaccination was 100%, in those
      immunized within a four-year interval a decline to 66% was recorded. Anti C
      antibodies after vaccination within a three-year interval were recorded in 75%
      subjects, in vaccinated subjects the authors detected antibodies during the first
      year after vaccination in 86% of the subjects. Natural anti A antibodies of the
      lowest titre 1:6 were recorded in four non-vaccinated subjects (22%). Naturally
      acquired anti B antibodies (B:2a:P1.2,P1.5) and anti C (C:2a:P1.2,P1.5) were not
      detected in any of the subjects.

PMID- 9919816
TI  - [Sporicidal effect of Presept and Chloramine B on Bacillus cereus spores].
AB  - The sporicidal effect of Presept was compared with Chloramine B on the spores of
      Bacillus cereus. Either compound was calibrated to the same concentration of
      active chlorine. While a portion of spore population after 4 hrs of treatment by
      Chloramine germinated and started to divide in a rich nutrient medium, the
      optical density of the culture inoculated with spores treated by Presept did not
      increase even after 7 hrs when exposed to the nutrient medium. Significant
      morphological differences were found in either population of spores. Spores
      treated by Presept lost the impermeability within 3 hrs in the nutrient medium
      but almost no postgerminative development was observed. However, a portion of
      spores treated by Chloramine B developed after germination within 3 hrs into
      vegetative cells. It seems that Presept does not block germination and/or loss of
      impermeability of spores, but prevents their postgerminative development and
      division.

PMID- 9919817
TI  - [Classification of microscopic fungi from the aspect of risk of infection in
      laboratory personnel].
AB  - The authors submit information on a new categorization of microscopic fungi
      causing human mycoses, as well as criteria of their classification in bio-risk
      groups (BioSafety Level-BSL) proposed by the European Confederation of Medical
      Mycology. According to the risk of infection of laboratory workers during
      handling of cultures isolated from biological specimens almost 400 species of
      fungi were divided into three groups (BSL 1 and BSL 2-fungi which can produce
      systemic infections in subjects with immunodeficiencies, or superficial
      infections in healthy subjects, BSL 3-fungi which can produce severe systemic
      infections also in healthy subjects). At the same time they express reservations
      to the classification of some species into groups.

PMID- 9919818
TI  - [Simultaneous occurrence of Toxoplasma gondii and Borrelia burgdorferi antibodies
      in patients with suspected toxoplasmosis or borreliosis].
AB  - In 1995-1997 the frequency of concurrent antibodies against Toxoplasma gondii and
      Borrelia burgdorferi was assessed in two groups of patients with different
      clinical symptoms. In 485 subjects the dermatological form (erythema migrans) of
      borreliosis was suspected, 877 subjects had clinical symptoms suggesting the
      nodular form of toxoplasmosis. The group of 485 subjects with suspected
      borreliosis comprised 199 (41%) subjects with the diagnosis confirmed by the
      serological finding and 286 (59%) subjects were serologically negative. During
      concurrent examination for toxoplasmosis a statistically significantly higher
      incidence of antitoxoplasmatic antibodies was recorded in patients with suspected
      borreliosis but without detected antibodies against Borrelia burgdorferi (29%)
      than in the group with both types of antibodies (11.5%), p < 0.001. The expected
      values of the incidence of antibodies against Toxoplasma gondii in the population
      (25%) were however not substantially surpassed by the actual values. In the group
      of 877 patients with suspected toxoplasmosis there were 114 subjects (13%) with
      acute toxoplasmosis, 300 subjects (34%) with anamnestic titres suggesting the
      chronic form of infection and 463 (53%) subjects where the infection with
      toxoplasmosis was not confirmed by serological tests. In the whole group,
      regardless whether the acute or chronic form of infection was involved, but also
      in the group without antitoxoplasmatic antibodies a significantly elevated number
      of subjects with antiborrelia antibodies (18-25%) was recorded as compared with
      the expected values of the incidence of antibodies against Borrelia burgdorferi
      in the population (10%), p < 0.001. In the discussion the authors deal with the
      possible causes of these phenomena.

PMID- 9919819
TI  - [An epidemic of salmonellosis in the First League Hockey Team].
AB  - The authors describe an epidemic of salmonellosis in 27 players and officials of
      the first league hockey team HC Kometa Brno which developed in conjunction with
      the consumption of a lunch in the facilities where the team usually takes its
      meals before competitions. The disease affected without exception all
      participants of the lunch, had a very severe course with high temperatures,
      weakness and intense diarrhoea sometimes with vomiting. The disease persisted for
      3-6 days, the loss of body weight caused mainly by dehydration was 4 to 13 kg.
      Faeces samples (3) of all affected patients were during the acute stage of the
      disease bacteriologically positive. Spontaneous debacilization took with a single
      exception 2-4 weeks. The disease was caused by Salmonella enteritidis, phagotype
      8. The source was not detected and the vehicle was most probably secondarily
      contaminated soup.

PMID- 9919820
TI  - [An anniversary of the Microbiology Institute of the Masaryk University Medical
      School in Brno].

PMID- 9919821
TI  - Inverse electrocardiography by simultaneous imposition of multiple constraints.
AB  - We describe two new methods for the inverse problem of electrocardiography. Both
      employ regularization with multiple constraints, rather than the standard single
      constraint regularization. In one method, multiple constraints on the spatial
      behavior of the solution are used simultaneously. In the other, spatial
      constraints are used simultaneously with constraints on the temporal behavior of
      the solution. The specific cases of two spatial constraints and one spatial and
      one temporal constraint are considered in detail. A new method, the L-Surface, is
      presented to guide the choice of the required pairs of regularization parameters.
      In the case when both spatial and temporal regularization are used
      simultaneously, there is an increased computational burden, and two methods are
      presented to compute solutions efficiently. The methods are verified by
      simulations using both dipole sources and measured canine epicardial data.

PMID- 9919822
TI  - Propagation in cardiac tissue adjacent to connective tissue: two-dimensional
      modeling studies.
AB  - The conditions for activation transmission across a region of extracellular space
      was demonstrated in two-dimensional preparations with results consistent with
      those previously seen in the one-dimensional fiber studies. In addition, one sees
      changes in action potential morphology which occur in the tissue nearest the
      connective-tissue border as well as changes in conduction velocity along the
      border. These results hinge on an adequate representation of the connective
      tissue region achieved by careful implementation of the boundary conditions in
      the intracellular and interstitial spaces and the expansion of the connective
      tissue discretization to a "double-tier network" description. Through a series of
      simulations, a clear dependence on fiber orientation is illustrated in the
      efficacy to transmit activation. The collision of a front with an embedded
      connective-tissue region was also examined. The results revealed that fibers
      aligned normal to a planar stimulus would more greatly disrupt the advancement of
      a planar front. Such pronounced disruptions have been shown to be proarrhythmic
      in the literature. The increasing evidence of the ability of connective tissue to
      transmit activation has implications in understanding spread of activation
      through infarcted tissues and through the healthy ventricular wall in the
      presence of connective-tissue sheets.

PMID- 9919823
TI  - Membrane polarization induced in the myocardium by defibrillation fields: an
      idealized 3-D finite element bidomain/monodomain torso model.
AB  - This study develops a three-dimensional finite element torso model with bidomain
      myocardium to simulate the transmembrane potential (TMP) of the heart induced by
      defibrillation fields. The inhomogeneities of the torso are modeled as eccentric
      spherical volumes with both the curvature and the rotation features of cardiac
      fibers incorporated in the myocardial region. The numerical computation of the
      finite element bidomain myocardial model is validated by a semianalytic solution.
      The simulations show that rotation of fiber orientation through the depth of the
      myocardial wall changes the pattern of polarization and decreases the amount of
      cardiac tissue polarized compared to the idealized analytic model with no fiber
      rotation incorporated. The TMP induced by transthoracic and transvenous
      defibrillation fields are calculated and visualized. The TMP is quantified by a
      continuous measure of the percentage of myocardial mass above a potential
      gradient threshold. Using this measure, the root mean square differences in TMP
      distribution produced by reversing the electrode polarity for anterior-posterior
      and transvenous electrode configurations are 13.6 and 28.6%, respectively. These
      results support the claim that a bidomain model of the heart predicts a change of
      defibrillation threshold with reversed electrode polarity.

PMID- 9919824
TI  - The nerve-electrode interface of the cochlear implant: current spread.
AB  - One of the fundamental facets of the cochlear implant that must be understood to
      predict accurately the effect of an electrical stimulus on the auditory nerve is
      the nerve-electrode interface. One aspect of this interface is the degree to
      which current delivered by an electrode spreads to neurons distant from it. This
      paper reports a direct mapping of this current spread using recordings from
      single units from the cat auditory nerve. Large variations were seen in the
      degree to which the different units are selective in responding to electrodes at
      different positions within the scala tympani. Three types of units could be
      identified based on the selectiveness of their response to the different
      electrodes in a linear array. The first type of unit exhibited a gradual increase
      in threshold as the stimulating site was moved from more apical to more basal
      locations within the scala tympani. The second type of unit exhibited a sharp
      local minimum, with rapid increases in threshold in excess of 6 dB/mm in the
      vicinity of the minimum. At electrode sites distant from the local minima the
      rate of change of the threshold approached that of the first type of units. The
      final type of unit also demonstrated a gradual change in threshold with changing
      electrode position, however, two local minima, one apical and one basal, could be
      identified. These three types are hypothesized to correspond to units which
      originate apical to the electrode array, along the electrode array and basal to
      the electrode array.

PMID- 9919825
TI  - A general solution for nonparametric control of a linear system using computer
      controlled infusion pumps.
AB  - Investigators have developed algorithms for use in computer-controlled infusion
      pumps (CCIP's) which dose intravenous drugs assuming multiexponential unit
      impulse response (UIR) function. However for many UIR multiexponential functions
      are at best an approximation. For almost all substances the early times after an
      impulse administration show complex profiles hardly described by multiexponential
      functions. For many later times also show departures from exponential decline. We
      derive a general approach for a CCIP which can be used with an arbitrary UIR
      function. A particular instance of the approach is based on a nonparametric
      representation of an UIR which uses spline functions. The approach is
      computationally simple, it can take into account desired constraints (for example
      no overshoot to avoid toxicity) and presents a solution to control concentrations
      of substances in a site different from the input site. Examples based on real
      lodocaine, veralipride, and thiopental data demonstrate the approach.

PMID- 9919826
TI  - Identification of electrically stimulated quadriceps muscles in paraplegic
      subjects.
AB  - This work establishes a method for the noninvasive in vivo identification of
      parametric models of electrically stimulated muscle in paralyzed individuals,
      when significant inertial loads and/or load transitions are present. The method
      used differs from earlier work, in that both the pulse width and stimulus period
      (interpulse interval) modulation are considered. A Hill-type time series model,
      in which the output is the product of two factors (activation and torque-angle)
      is used. In this coupled model, the activation dynamics depend upon velocity.
      Sequential nonlinear least squares methods are used in the parameter
      identification. The ability of the model, using identified time-varying
      parameters, to accurately predict muscle torque outputs is evaluated, along with
      the variability of the identified parameters. This technique can be used to
      determine muscle parameter models for biomechanical computer simulations, and for
      real-time adaptive control and monitoring of muscle response variations such as
      fatigue.

PMID- 9919827
TI  - Mean-shape vector quantizer for ECG signal compression.
AB  - A direct waveform mean-shape vector quantization (MSVQ) is proposed here as an
      alternative for electrocardiographic (ECG) signal compression. In this method,
      the mean values for short ECG signal segments are quantized as scalars and
      compression of the single-lead ECG by average beat substraction and residual
      differencing their waveshapes coded through a vector quantizer. An entropy
      encoder is applied to both, mean and vector codes, to further increase
      compression without degrading the quality of the reconstructed signals. In this
      paper, the fundamentals of MSVQ are discussed, along with various parameters
      specifications such as duration of signal segments, the wordlength of the mean
      value quantization and the size of the vector codebook. The method is assessed
      through percent-residual-difference measures on reconstructed signals, whereas
      its computational complexity is analyzed considering its real-time
      implementation. As a result, MSVQ has been found to be an efficient compression
      method, leading to high compression ratios (CR's) while maintaining a low level
      of waveform distortion and, consequently, preserving the main clinically
      interesting features of the ECG signals. CR's in excess of 39 have been achieved,
      yielding low data rates of about 140 bps. This compression factor makes this
      technique especially attractive in the area of ambulatory monitoring.

PMID- 9919828
TI  - Depth of anesthesia estimation and control.
AB  - A fully automated system was developed for the depth of anesthesia estimation and
      control with the intravenous anesthetic, Propofol. The system determines the
      anesthesia depth by assessing the characteristics of the mid-latency auditory
      evoked potentials (MLAEP). The discrete time wavelet transformation was used for
      compacting the MLAEP which localizes the time and the frequency of the waveform.
      Feature reduction utilizing step discriminant analysis selected those wavelet
      coefficients which best distinguish the waveforms of those responders from the
      nonresponders. A total of four features chosen by such analysis coupled with the
      Propofol effect-site concentration were used to train a four-layer artificial
      neural network for classifying between the responders and the nonresponders. The
      Propofol is delivered by a mechanical syringe infusion pump controlled by
      Stanpump which also estimates the Propofol effect-site and plasma concentrations
      using a three-compartment pharmacokinetic model with the Tackley parameter set.
      In the animal experiments on dogs, the system achieved a 89.2% accuracy rate for
      classifying anesthesia depth. This result was further improved when running in
      real-time with a confidence level estimator which evaluates the reliability of
      each neural network output. The anesthesia level is adjusted by scheduled
      incrementation and a fuzzy-logic based controller which assesses the mean
      arterial pressure and/or the heart rate for decrementation as necessary. Various
      safety mechanisms are implemented to safeguard the patient from erratic
      controller actions caused by external disturbances. This system completed with a
      friendly interface has shown satisfactory performance in estimating and
      controlling the depth of anesthesia.

PMID- 9919829
TI  - A low-complexity intracardiac electrogram compression algorithm.
AB  - Implantable cardioverter defibrillators (ICD's) detect, diagnose and treat the
      potentially fatal heart arrhythmias known as bradycardia, ventricular tachycardia
      (VT), and ventricular fibrillation (VF) in cases where these arrhythmias are
      resistant to surgical and drug-based treatments by direct sensing and electrical
      stimulation of the heart muscle. Since the ICD is implanted, power consumption,
      reliability, and size are severe design constraints. This paper targets the
      problems associated with increasing the signal recording capabilities of an ICD.
      A data-compression algorithm is described which has been optimized for low power
      consumption and high reliability implementation. Reliance on a patients
      morphology or that of a population of patients is avoided by adapting to the
      intracardiac electrogram (ICEG) amplitude and phase variations and by using
      adaptive scalar quantization. The algorithm is compared to alternative
      compression algorithms which are also patient independent using a subset of VT
      arrhythmias from a data base of 146 patients. At low distortion the algorithm is
      closest to the Shannon lower bound achieving an average of 3.5 b/sample at 5%
      root mean square distortion for a 250-Hz sample rate. At higher distortion vector
      quantization and Karhunen-Loeve Transform approaches are superior but at the cost
      of considerable additional computational complexity.

PMID- 9919830
TI  - Higher-order spectral analysis of burst patterns in EEG.
AB  - Burst suppression patterns in electroencephalograms (EEG's) have been observed in
      a variety of situations including recovery of a subject from a traumatic brain
      injury. They are associated with grave prognostic outcomes in neonates. We study
      power spectral parameters and bispectral parameters of the EEG at baseline,
      during early recovery from an asphyxic arrest (EEG burst patterns) and during
      late recovery after EEG evolves into a more continuous activity. The bicoherence
      indexes, which indicate the degree of phase coupling between two frequency
      components of a signal, are significantly higher within the delta-theta band of
      the EEG bursts than in the baseline or late recovery waveforms. The bispectral
      parameters show a more detectable trend than the power spectral parameters. In
      the second part of the study, we looked into the possibility of higher (> 2)-
      order nonlinearities in the EEG bursts using the diagonal slices of the
      polyspectrum. The diagonal elements of the polyspectrum reveal the presence of
      self-frequency and self-phase coupling of orders higher than two in majority of
      the EEG bursts studied. The bicoherence indexes and the diagonal elements of the
      polyspectrum strongly indicate the presence of nonlinearities of order two and in
      many cases higher, in the EEG generator during episodes of bursting. This
      indication of nonlinearity in EEG signals provides a novel quantitative measure
      of brain's response to injury.

PMID- 9919831
TI  - Dominant pattern extraction from 3-D kinematic data.
AB  - A new method for the extraction of a repeating pattern in cyclic biomechanical
      data is proposed--singular value decomposition pattern analysis (SVDPA). This
      method is based on the recent work of Kanjilal and Palit [14], [15] and can be
      applied to both contiguous and repeated trials without being constrained to be
      strictly periodic. SVDPA is a data-driven approach that does not use a
      preselected set of basis functions; but instead utilizes a data matrix with a
      special structure to identify repeating patterns. Several important features of
      SVDPA are described including its close relationship to the Kahunen-Loeve
      transform. The dominant pattern is defined as the average energy component (AEC).
      The AEC is obtained from the SVD of the data matrix and is equivalent to the
      optimal [maximal signal-to-noise ratio (SNR)] ensemble average pattern. The
      degree of periodicity and SNR for the AEC are defined explicitly from the
      singular values of the data matrix. We illustrate the usefulness of SVDPA for
      dominant pattern extraction by applying it to the quasiperiodic three-dimensional
      trajectory of a marker attached to the trunk during treadmill locomotion. The AEC
      obtained for the normalized trajectory and error estimates at each point suggests
      that SVDPA could be a useful tool for the extraction of the fine details from
      cyclic biomechanical data.

PMID- 9919832
TI  - Real-time 3-D model-based navigation system for endoscopic paranasal sinus
      surgery.
AB  - This paper presents a three-dimensional (3-D)-model-based navigation system for
      endoscopic sinus surgery treating paranasal sinusitis. Endoscopic surgery is
      becoming more common because of its low invasiveness. Its problem with
      disorientation, however, is one of the toughest barriers for the novice and may
      lead even an expert to commit serious surgical errors, e.g., causing
      cerebrospinal fluid (CSF) leakage or blinding the patient. To prevent such
      complications and optimize training, our system aids in navigation by showing a
      single perspective view of the patient and the endoscope models. This virtual
      endoscope has a viewing cone with a simulated light to indicate the viewing
      direction and visual field in real-time. The system's three clipping planes
      automatically follow the endoscope and help keep the surgeon aware of the
      endoscope's actual position. An experiment comparing the system to conventional
      navigation using a triplanar display showed that the perspective view was
      referenced very frequently, giving a positive impressions, while the triplanar
      display was almost completely ignored, apparently because it was too difficult to
      interpret immediately.

PMID- 9919834
TI  - Idiopathic pulmonary fibrosis: prognostic indicators.

PMID- 9919833
TI  - Lack of effects on heart rate and blood pressure in ketamine-anesthetized rats
      briefly exposed to ultra-wideband electromagnetic pulses.
AB  - Fourteen Sprague-Dawley rats were exposed to pulses produced by a Bournlea ultra
      wideband (UWB) pulse generator (rise time, 318-337 ps; maximum E field, 19-21
      kV/m). Exposures at a repetition frequency of 1 kHz for 0.5 s or to repetitive
      pulse trains (2-s exposure periods alternating with 2 s of no exposure, for a
      total of 2 min) resulted in no significant changes in heart rate or mean arterial
      blood pressure. These results suggest that acute whole-body exposure to UWB
      pulses does not have a detrimental effect on the cardiovascular system.

PMID- 9919835
TI  - Response to steroid therapy in patients of idiopathic pulmonary fibrosis: a
      retrospective analysis.
AB  - Fifty four patients of idiopathic pulmonary fibrosis were evaluated
      retrospectively to see the effect of prednisolone therapy on the course of the
      disease. The diagnosis was established based on clinical history, physical
      findings, radiology, HRCT, spirometry and transbronchial biopsy whenever
      possible. Each patient received prednisolone 1 mg/kg/day for 6 weeks which was
      then tapered gradually till a maintenance dose was achieved. Six patients (11.1%)
      died within 3 months (3 within 1 month) of presentation because of rapid
      progression of the disease and inspite of addition of intravenous methyl
      prednisolone. Improvement in symptomatology, particularly cough and dyspnoea,
      were quite variable. Twenty six (48.1%) reported subjective improvement by 20-80%
      of the initial symptoms. However, in most cases this improvement was for the
      initial 3-6 months of therapy. Subsequently either they deteriorated or remained
      stable. There was no clinical improvement in the remaining 20 patients
      (improvement in symptoms by 0 to less than 20%). There was no radiological
      improvement in any case. FVC improved at 3 months only after treatment compared
      to the baseline values (p < 0.01). However, subsequently there was no significant
      improvement in the lung function. Of the 37 cases whose initial FVC value could
      be obtained, 8 patients (21.6%) showed an improvement by more than 20% of their
      baseline values during their follow up period. Of these, 4 had the improvement by
      3 months; 3 by 6 months; and one showed improvement at 1 year and 6 months. Five
      patients (13.5%) had a decrease in FVC by 10% or more during their follow up. One
      patient developed sputum positive pulmonary tuberculosis nine months after
      steroid therapy.

PMID- 9919837
TI  - Theophylline clearance in undernourished asthma patients.
AB  - Theophylline clearance is altered by many drugs and diseases that may be
      associated with undernutrition. Therefore, we studied theophylline clearance in
      12 undernourished [body mass index (BMI) less than 19] and 12 well nourished
      asthma patients (body mass index more than 19). Uncoated theophylline tablet (200
      mg, 300 mg dose 5 mg/kg approx) was administered orally to each asthma patient
      after 12 hours overnight fasting. Serum theophylline concentrations were
      estimated after 2, 4, 6, 8 hours of drug administration and it was calculated
      from log conc: time curve. Undernourished asthma patients had a mean theophylline
      clearance of 85.6 (SE = 6.2) ml/hr/kg while it was 125.6 (SE = 3.8) ml/hr/kg in
      well-nourished asthma patients. The difference between two groups was highly
      significant (p < 0.01). We conclude that theophylline clearance is significantly
      lower in undernourished asthma patients and they will require a lower maintenance
      dose of theophylline.

PMID- 9919836
TI  - Inoperable non-small cell lung cancer: palliative radiotherapy with two weekly
      fractions.
AB  - Thirty seven cases (30 males; 7 females) of advanced non-small cell lung cancer
      were treated with short course of palliative radiotherapy. All the patients were
      inoperable. Their main symptoms were related to primary intrathoracic disease and
      poor performance status. Radiotherapy was delivered to a total dose of 17 Gy in
      two fractions one week apart. Ninety percent of the patients had cough, 50%
      complained of haemoptysis, 45% chest pain and 30% breathlessness. Palliation of
      main symptoms was achieved in majority of the patients, more than 90% in
      haemoptysis, 60% in cough, 70% in chest pain and 50% in breathlessness. Mean
      duration of palliation was four months and performance status improved in 60% of
      the patients. Short course radiotherapy of 17 Gy in two weekly fractions is
      recommended in patients with advanced non-small cell lung cancer (NSCLC) having
      poor performance status.

PMID- 9919838
TI  - Epidemiology of childhood asthma.

PMID- 9919839
TI  - Imaging in primary pulmonary hypertension.

PMID- 9919840
TI  - Flow volume loops: postural significance.
AB  - Upper airway obstruction is an important but often unrecognised cause of dyspnoea
      and ventilatory failure. Flow volume loop remains the most sensitive method to
      detect upper airway obstruction. We report a patient with Hashimoto's thyroiditis
      who showed evidence of upper airway obstruction on the flow volume loop only in
      the supine position. It is important to recognise as it may be missed during the
      conventional method of performing a pulmonary function test in sitting posture
      and also because surgical intervention should be considered in patients with
      tracheoesophageal compression due to a thyroid swelling.

PMID- 9919841
TI  - Diffuse pulmonary calcinosis and multiple soft tissue calcification in renal
      failure patient with pathological femoral fracture.
AB  - The rare occurrence of diffuse pulmonary calcinosis is described with case
      illustration of a patient who presented with a pathological femoral fracture
      during end-stage renal failure. Associated metastatic soft tissue calcification
      with parathyroid hyperplasia requiring parathyroidectomy was observed.
      Roentgenologic evidence of hyperparathyroidism with osteitis fibrosa cystica and
      a high product of the calcium and phosphate values were indications for the
      parathyroidectomy. Recent literature review of pulmonary calcinosis and multiple
      soft tissue calcification is also presented.

PMID- 9919842
TI  - Metachronous bronchogenic carcinoma in a patient treated for cervical cancer.
AB  - A case of metachronous malignancy in an elderly postmenopausal lady is presented.
      She had previously been successfully treated for squamous cell carcinoma of the
      cervix and now four years later, presented with a right lower lobe lung abscess.
      On evaluation she was found to have a small cell carcinoma of the lung involving
      the right intermediate and right lower lobe bronchus. She improved clinically and
      radiologically with parenteral antibiotics, combination chemotherapy and local
      external radiotherapy.

PMID- 9919843
TI  - Pneumomediastinum: a rare complication of brachial plexus block.
AB  - Pneumomediastinum, a rare complication of brachial plexus block in a young male
      is reported.

PMID- 9919844
TI  - Dangerous liaisons: combinations that kill.

PMID- 9919845
TI  - The use of designated drivers by US college students: a national study.
AB  - A representative national sample of students attending 4-year colleges in the
      United States reported whether they had served as or had ridden with a designated
      driver in the past 30 days and how much alcohol they had consumed the last time
      they used this prevention strategy. Among drinkers (those who had consumed
      alcohol in the past year), 36% said they had served as a designated driver in the
      past 30 days; of these, 40% said they usually binged when they drank but had not
      done so the last time they served as the designated driver, with the vast
      majority either abstaining or having 1 drink. Among drinkers, 37% reported riding
      with a designated driver in the past 30 days; of these, 22% said they did not
      usually binge but did so the last time they had a designated driver because they
      had had 1 or more extra drinks. Among college students, using designated drivers
      is now a well-established strategy for avoiding impaired driving.

PMID- 9919846
TI  - Descriptive epidemiology of dozing and driving in a college student population.
AB  - Driving while fatigued is a serious risk-taking behavior among college students.
      Accident data were reviewed and a behavioral risk factor survey undertaken at a
      large private university. The findings indicated that 86 motor vehicle fatalities
      occurred among students at the university in the last 15 years. The authors
      estimated that falling asleep at the wheel may have caused 62 of these accidents
      and that more than 3,000 students experience a driving-dozing incident annually,
      resulting in a yearly average of 200 injury accidents and 4 fatalities.
      Descriptive epidemiologic data are presented and implications for health
      promotion efforts are discussed.

PMID- 9919847
TI  - Abortion attitudes as determinants of perceptions regarding male involvement in
      abortion decisions.
AB  - Abortion decisions have a potentially meaningful effect on the lives of men.
      Previous research suggests that both men and women generally believe that men
      have the right to be involved in such decisions. However, very little research
      attention has been devoted to identifying individual difference correlates of
      discrepant levels of endorsement for male involvement in abortion decisions. The
      extent to which abortion attitudes (on a pro-choice to pro-life continuum),
      conceptualization of abortion as strictly a female issue, and interest in the
      issue operate as effective predictors of the appropriate level of male
      involvement in abortion decisions was examined in a sample of 1,387 college
      students. Results of a multiple regression analysis revealed that 44% of the
      variance in male involvement scores was explained by the predictor variables.

PMID- 9919848
TI  - Awareness and utilization of the hepatitis B vaccine among young men in the Ann
      Arbor area who have sex with men.
AB  - The authors conducted a preliminary assessment of hepatitis B vaccination rates
      among men 18- to 37-years-old who have sex with men in a college town to
      determine what proportion were willing to be vaccinated. Participants, who were
      sampled in gay bars, gay advocacy groups, a swim team, and a dance club,
      completed a 25-item questionnaire. Sixty-seven percent were aware of the
      hepatitis B vaccine, yet only 22% had received the full series of three
      injections; only 37% had been tested for the virus. On a scale of 1 to 10 for
      willingness to be vaccinated (10 being most willing), 58% indicated a 10 (M =
      8.5). Thirty percent indicated they received safer sex information from
      university health services, and 14% reported they had received hepatitis B
      vaccination information there. Hepatitis B vaccination of men who have sex with
      men in college towns should be a high priority for university health services.

PMID- 9919849
TI  - Psychological and academic functioning in college students with attention deficit
      hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) has been increasingly recognized
      as a valid adult diagnosis. Yet the impairments related to ADHD in college
      students have received little scholarly attention. Psychological and academic
      impairments in college students not previously diagnosed with ADHD were assessed
      in a retrospective chart review, using specifically defined diagnostic criteria,
      and compared with a control group. Students with ADHD had a significantly lower
      mean grade point average, were more likely to be on academic probation, and
      reported significantly more academic problems. Measures of psychological
      impairment in the ADHD group were not significantly different from those in the
      control group. College students diagnosed with ADHD had a specific pattern of
      academic impairment. The problems of these students, compared with other groups
      of children and adults with ADHD, appeared to be more related to a type of
      learning disorder than to the conceptualization of ADHD in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV).

PMID- 9919850
TI  - Greeks and athletes: who drinks more?

PMID- 9919851
TI  - Antidepressants and drug interactions: prescriber beware.

PMID- 9919852
TI  - The impact of education and heart attack on smoking cessation among middle-aged
      adults.
AB  - Considerable evidence supports the premise that higher levels of education lead
      to enhanced health, including protective health behaviors. This paper focuses on
      how education affects one health behavior known to lead to enhanced health: the
      cessation of smoking. In particular, the authors examine the extent to which
      education influences the decision by middle-aged adults to quit smoking following
      a heart attack, a potentially life-threatening health event. We first hypothesize
      that middle-aged adults with more formal education will stop smoking more readily
      than people with less formal education following the experience of a heart
      attack. Second, we ask what other factors might underlie and explain that
      hypothesized effect. Using longitudinal data, the authors track changes in
      individual smoking behaviors after a heart attack among preretirement-age
      Americans. We control for documented correlates of smoking and heart attack plus
      other factors associated with education, heart attack, and smoking that may also
      influence whether a person quits smoking. In addition to confirming evidence on
      the education-health association as well as the documented connection between
      heart attack and smoking cessation, this study provides a surprising twist on
      those links: Our results show that the move to quit smoking following the
      experience of a heart attack among middle-aged adults is significantly and
      dramatically moderated by their level of educational attainment.

PMID- 9919853
TI  - Education and health in the Czech Republic.
AB  - Researchers in the United States have found that education and health are
      related. This relation may be due to the better market position of the educated,
      their greater store of personal and social resources, and/or their healthier
      lifestyle. These three connections between education and health are tested in the
      Czech Republic with three waves of panel data. We regress self-reports of health
      and physical functioning in 1994 on multiple indicators of market position in
      1994, change in market position from 1989 to 1994, personal/social resources and
      health lifestyle with demographic controls. These regressions are followed by a
      longitudinal analysis of changes in panel members' health and physical
      functioning between 1994 and 1996. The cross-sectional results are similar to
      those in the United States with important exceptions. Unlike the United States,
      market position does fully mediate the relation between education and health in
      the Czech Republic, largely through subjective feelings regarding market
      position. The longitudinal analysis shows that prior health and physical
      functioning mediate the effect of education on health and physical functioning in
      1996.

PMID- 9919854
TI  - Consequences of retirement activities for distress and the sense of personal
      control.
AB  - We compare retirement with full-time employment on four forms of engaging
      activity and examine the consequences of retirement activities for the sense of
      control and psychological distress. We use a 1995 U.S. national telephone
      probability sample of 2,592 respondents with an oversample of persons aged sixty
      and older. In comparison to the activities of full-time employees, those of
      retirees are more alienating on some aspects but more engaging on others. Retiree
      activities are more routine, provide less of a chance to learn new things,
      provide less positive social interaction with others, and they are especially
      unlikely to involve problem-solving. However, retirees' activities are also
      equally enjoyable and more autonomous compared to those of full-time workers.
      Autonomous activities, fulfilling activities which are enjoyable and provide the
      opportunity to learn new things, and integrated activities are all positively
      associated with a sense of control and negatively associated with psychological
      distress. However, solving problems is associated with both high levels of
      control and high levels of distress. Retirees have a significantly lower sense of
      control than do full-time employees, in large part because of the characteristics
      of their daily activities. At the same time, retirees do not have significantly
      higher levels of psychological distress.

PMID- 9919855
TI  - The effects of stigma on the psychological well-being and life satisfaction of
      persons with mental illness.
AB  - Building on modified labeling theory, I examine the relationships between stigma,
      psychological well-being, and life satisfaction among persons with mental
      illness. The study uses longitudinal data from 610 individuals in self-help
      groups and outpatient treatment. Results from cross-sectional and lagged
      regression models show adverse effects of stigma on the outcomes considered.
      However, much of the effects of anticipated rejection are due to discriminatory
      experiences. The results also indicate that stigma is related to depressive
      anxiety types of symptoms but not psychotic symptoms. Although the findings show
      that the negative effect of stigma on life satisfaction is partly mediated by
      self-concept, reciprocal effects models indicate that the relationship between
      self-concept and life satisfaction is bi-directional. The study suggests ways in
      which stigma processes need to be explored in greater detail.

PMID- 9919856
TI  - Voluntary association membership and psychological distress.
AB  - Does voluntary association reduce psychological distress and can these effects be
      distinguished from the more commonly recognized benefits of social support? This
      paper attempts to answer this question by reporting the results of an
      investigation, guided by the stress process model, into the effects of voluntary
      group membership on psychological distress. I conducted this research through a
      secondary analysis of a community sample of 850 persons residing in southwestern
      Ontario in 1984. I find that voluntary group membership results in a reduction in
      depressive symptoms for men and women ranging in age from 22-89. In addition,
      voluntary group members suffer lower levels of depressive symptoms in the
      presence of increasing stress burdens than do those who are not group members,
      indicating stress buffering effects. Controlling for individual psychosocial
      resources including mastery, self-esteem, and social support does not reduce
      these effects, thus leading to the conclusion that voluntary association
      membership itself makes a unique contribution to distress reduction.

PMID- 9919857
TI  - Physician satisfaction in a changing health care environment: the impact of
      challenges to professional autonomy, authority, and dominance.
AB  - For some time, sociologists have debated whether physicians still retain
      dominance in the health care world, public faith in their moral and scientific
      authority, and the autonomy to set work conditions and make clinical decisions.
      Using ideas derived from this debate, we analyze the impact of changes in the
      health care environment on physician satisfaction. Our data come from a mailed
      survey of 510 Arizona physicians. Our results show that background physician
      attributes did not predict satisfaction, nor did most organizational attributes.
      However, participation in IPAs (Individual Practice Associations) predicted
      higher satisfaction, while payment according to a third party payer's fee-for
      service schedule predicted lower satisfaction. In addition, physicians were more
      likely to be satisfied if they wrote the orders that non-physicians had to
      follow, were paid what they wanted, did not need to subordinate their clinical
      judgment to that of non-physicians, and believed that their patients had
      confidence in physicians. Our conclusions discuss both theoretical and policy
      implications of our findings.

PMID- 9919858
TI  - Organizational characteristics associated with agency position in community care
      networks.
AB  - This study examines how organizational characteristics affect agency
      participation and centrality in community service networks. We find that the
      network structure of agency relations varies for administrative and client
      related activities among the 69 agencies studied, which include all but the most
      isolated agencies serving people with physical disabilities in a single
      community. In identifying structurally equivalent groups using network analysis,
      we find that all types of agencies except HMOs are found throughout community
      service networks. Analyses show that among the five types of relations, minimal
      intergroup activity occurs within funding and planning networks and that
      organizational size and ownership are the best organizational predictors of
      network location and centrality. Non-profits are the most central for planning
      and client referrals, and large agencies are the most central for funding. We
      explore the implications of these findings, particularly for sustaining
      cooperation within the service networks and for the role of non-profits and
      medical providers in the community.

PMID- 9919859
TI  - Butorphanol pharmacokinetics in a CRPS patient.

PMID- 9919860
TI  - The use of calcitonin in the treatment of metastatic bone pain.

PMID- 9919862
TI  - Health policy, health services, and cancer pain management in the New South
      Africa.
AB  - In 1982, the World Health Organization (WHO) identified inadequate relief from
      cancer pain as an international health problem. WHO recommended that governments
      develop and implement national policies and programs for cancer pain relief. This
      report evaluates national health policy and the systems of health care delivery
      in relation to cancer pain management in the new South Africa. This field study
      included multiple methods of data collection: analysis of documents, field trips
      with participant observation in sites of care delivery, focused interviews, and
      in-depth interviews of key informants. The purposive sample of key informants (n
      = 33) represented multiple stakeholders in a variety of settings. Strengths of
      the developing health policy include specific recommendations related to
      palliative care; the shift to universal primary care; policies to support drug
      availability; the inclusion of morphine and codeine as essential drug at the
      primary health care level; and the development of a national standard related to
      cancer pain management. Health services are characterized by two parallel systems
      of care (private and public) with numerous vestiges of the inequities of
      apartheid. The management of pain varies by provider and setting; major problems
      with access exist in the rural areas. Health services in South Africa have been
      plagued by inequity and inadequate resources. New health policies have set a path
      to ensure universal access to health care including palliative care for cancer.
      Their successful implementation is the next necessary step toward improving
      health services and alleviating the suffering of increasing numbers of
      individuals with cancer.

PMID- 9919861
TI  - End-of-life decision-making in the hospital: current practice and future
      prospects.
AB  - Chart review of patients who died in the hospital was used to describe the
      pattern of end-of-life decision-making and care for hospitalized dying patients
      and to propose a structured process of assessing the suitability of patients for
      palliative care. The setting was a large urban academic medical center, and the
      sample comprised 200 of 205 consecutive adult deaths during the first 4 months of
      1996. The main outcome measures were identification of the patient as dying, do
      not-resuscitate (DNR) orders, and comfort care plans. Charts of 72% of the
      patients had evidence that they were considered dying. DNR orders were in place
      for 77% of all the patients, and 46% had comfort care plans. Presence of a health
      care proxy was significantly associated with DNR orders and comfort care plans (P
      < 0.001). On average, comfort care plans were put in place 15 days after
      admission, as compared with an overall mean length of stay of 17 days.
      Substantial proportions of patients with comfort care plans continued to receive
      antibiotics (41%) and blood draws (30%). Only 13% of the patients on mechanical
      ventilation and 19% of those on artificial nutrition and hydration underwent
      withdrawal of these interventions prior to death. These findings suggest
      opportunities and challenges for improving practice patterns for hospitalized
      dying patients. We recommend several measurable objectives for evaluating end-of
      life decision-making and care and propose the development of a goals of care
      assessment tool to guide appropriate transitions from life-sustaining treatment
      to comfort care and plan palliative services.

PMID- 9919863
TI  - The assessment of cancer pain in north India: the validation of the Hindi Brief
      Pain Inventory--BPI-H.
AB  - The status of pain treatment for cancer patients in India is largely
      undocumented. Although many languages and dialects are spoken throughout the
      country, millions of persons in North India speak Hindi. This project developed
      and validated a Hindi version of the Brief Pain Inventory (BPI-H), a short
      measure of pain and pain interference that has been shown to be relatively free
      of cultural or linguistic influences. In the validation process, we were able to
      administer both the Hindi and English versions of the BPI to a sample of
      bilingual (Hindi and English) patients. The English and Hindi versions of the BPI
      were very similar in their psychometric properties, supporting the reliability
      and construct validity of the Hindi version. As with other language versions of
      the BPI, factor analysis of the BPI-H items results in severity and interference
      subscales. We followed the validation with an examination of the status of cancer
      pain management in a major northern Indian cancer center, based on 200 patients
      with pain who spoke only Hindi. Using a conservative measure of analgesic
      prescription adequacy (the Pain Management Index), three-fourths of Hindi
      speaking cancer patients in this study were inadequately treated by World Health
      Organization (WHO) recommendations. The results of this study encourage the
      development of other forms of the BPI in the many languages of India, and the use
      of the instrument in studies of the epidemiology and treatment of cancer pain.

PMID- 9919864
TI  - Fatigue and its associated factors in ambulatory cancer patients: a preliminary
      study.
AB  - Although fatigue is considered to be one of the major causes of distress among
      cancer patients, little is known about its association with other factors, such
      as demographic, medical, and psychosocial factors. A total of 455 ambulatory
      cancer patients completed the Profile of Mood States (POMS) scale, which includes
      a fatigue subscale. Other information was obtained in an interview. The results
      of a multiple regression analysis suggested that sex, education, employment
      status, the size of the household, the performance status, and depressive mood
      were associated with fatigue. Our findings reveal that the fatigue experienced by
      cancer patients may be determined by multiple factors, including demographic,
      physical, and psychological factors.

PMID- 9919865
TI  - Documentation of severe pain, opioid doses, and opioid-related side effects in
      outpatients with cancer: a retrospective study.
AB  - Pain severity, prescribed opioids including "rescue" medication for breakthrough
      pain, bowel movements, and laxative prescription were evaluated in 54 cancer
      patients treated in an outpatient department devoted to hematology and oncology
      during 1996. Median number of visits per patient was 5.5 (range 1-48), and median
      duration of patient care during opioid therapy was 44.5 days (range 1-363). Pain
      severity and opioid dose were not documented, or documented in less than 25% of
      visits, in 62.9% and 48.2%, respectively. Rescue doses for breakthrough pain,
      laxative prescription and bowel movements were never mentioned in 70.4%, 68.5%,
      and 87% respectively, of all patient charts. Only 3 of 12 physicians documented
      pain severity in more than 15% of visits, and opioid dose was recorded in more
      than 30% of all visits only by four physicians. Rescue doses for breakthrough
      pain, laxative prescription, and bowel movements were never or only scarcely
      documented by all physicians. Pain measurement using a visual analog scale was
      recorded by one physician. Our data show inadequate documentation of important
      aspects of cancer pain in a large outpatient department of hematology and
      oncology. These deficiencies may have a major negative impact on the quality of
      cancer pain treatment.

PMID- 9919866
TI  - The application of goal attainment scaling in chronic pain settings.
AB  - Although the multidimensional nature of chronic pain has been recognized since
      the 1960s, pain management continues to reflect a biomedical model for many
      chronic pain patients. The application of a biopsychosocial approach would be
      aided by measurement tools that reflect the multidimensional nature of pain,
      facilitate interdisciplinary care planning, and focus treatment on the
      consequences of pain that are important to patients. Goal Attainment Scaling
      (GAS) is an individualized health outcome measure that is suitable for health
      problems that warrant a multidimensional and individualized approach to treatment
      planning and outcome measurement. This paper describes the use of GAS as a
      treatment and research tool in cancer pain, pediatric pain, work-related
      nonmalignant pain, and geriatric pain. Unlike the typical process where goals are
      not explicitly stated, GAS allows goals to be stated in a systematic measurable
      manner that is relevant and meaningful for each patient, and that can guide
      individual treatment planning. GAS is an appropriate technique for guiding and
      monitoring the treatment of individual chronic pain patients, and may provide a
      useful tool for evaluating chronic pain programs.

PMID- 9919867
TI  - Massage therapy for low back pain: a systematic review.
AB  - Massage therapy is frequently employed for low back pain (LBP). The aim of this
      systematic review was to find the evidence for or against its efficacy in this
      indication. Four randomized clinical trials were located in which massage was
      tested as a monotherapy for LBP. All were burdened with major methodological
      flaws. One of these studies suggests that massage is superior to no treatment.
      Two trials imply that it is equally effective as spinal manipulation or
      transcutaneous electrical stimulation (TES). One study suggests that it is less
      effective than spinal manipulation. It is concluded that too few trials of
      massage therapy exist for a reliable evaluation of its efficacy. Massage seems to
      have some potential as a therapy for LBP. More investigations of this subject are
      urgently needed.

PMID- 9919868
TI  - Opioid-induced itching: morphine sulfate and hydromorphone hydrochloride.
AB  - We describe a case of severe morphine-induced itch unrelieved by antihistamines,
      which responded to a change to hydromorphone. The possible mechanisms of opioid
      induced itch are briefly discussed. It is unclear if it is due to histamine
      release, an opioid-receptor mediated effect, or idiosyncratic drug reaction.

PMID- 9919869
TI  - Old, female, and rural. Introduction.

PMID- 9919870
TI  - Subjective realities of rural older women's lives: a case study.
AB  - This paper presents and analyzes the subjective reality of a single older rural
      woman through her telling of her life story and open-ended interviews. This case
      study is used to demonstrate how a rural woman experiences a positive life
      experience while living with poverty, poor health, and numerous challenges and
      losses. The case was selected from the multiphase Rural Older Women's Project
      completed in rural Minnesota in 1986 and 1987. This representation shows the
      respondent living her later life and adjusting to old age in the same ways she
      has always faced life's challenges-with stoicism and tenacity, as well as
      patience and good humor. In the telling of her life story we recognize key values
      of rural older women including independence and privacy, balanced with a clear
      sense of the importance of relationships with others, and a closeness to the
      land. The views of informal and formal systems of service delivery are discussed
      and implications explored for the development of formal services which will more
      effectively meet the needs of rural older women.

PMID- 9919871
TI  - "Staying close to shore": a context for older rural widows' use of health care.
AB  - Access to health care has been considered central to understanding older rural
      adults' utilization of health services. Access has been measured in terms of
      distance to care, use of care, and barriers to care; because older persons'
      relevant perceptions have received little attention, the validity of the typical
      access constructs is questionable. During a phenomenological study of their
      experiences of living alone at home, eight older rural widows shared perceptions
      about the locales where they received primary care and specialty care. A facet of
      their life-worlds, "staying close to shore," was seen as a frame of reference for
      their perceptions and as a general context for health care utilization. The
      implications of "staying close to shore" are discussed in relation to
      conventional conceptualizations of access.

PMID- 9919872
TI  - Rural women's economic realities.
AB  - The economic position of many elders has improved over the past few decades.
      Several groups of elders remain disadvantaged, however, including nonmetropolitan
      elders and women in any setting. This study examines differences in household
      income and poverty rates for metropolitan and nonmetropolitan women ages 55 and
      over in 1970, 1980 and 1990. Comparison of median incomes for women the same age
      across birth cohorts reveals that much of the improvement in women's economic
      well-being occurs because younger cohorts have higher incomes when they enter
      older ages. There also is evidence that incomes decline as the cohort ages.
      Nonmetro women have lower incomes and higher poverty rates than metro women in
      every comparison, even when demographic characteristics are controlled. While the
      metro/nonmetro income gap declines from 1970 to 1980, it increases from 1980 to
      1990. The largest income gap occurs for women ages 55 to 64 in 1990, the youngest
      cohort examined, offering no evidence to support convergence of household incomes
      among metro and nonmetro older women in the near future.

PMID- 9919873
TI  - Family relationships of older, rural women: stability and change.
AB  - The purpose of the study was to examine stability and change in family
      interaction patterns (availability, interaction, and assistance) of older, rural
      women as they moved from young-old to late old age. Women (N = 96) were
      interviewed at two times, twelve years apart. Although there were family network
      losses, most notably loss of spouse and siblings, family availability and contact
      showed more stability than change. By late old age, the women were receiving
      significantly more help from adult children relative to what they gave. Proximity
      of the adult child was most salient as a predictor of help received from children
      at both Times 1 and 2. Quality of the adult child relationship was higher for
      women who received more types of help from adult children at Time 2. The findings
      suggest that with loss of family members, proximate kin may take up the slack in
      providing support to rural women of advanced age.

PMID- 9919874
TI  - Critical review: synthesis and recommendations for research, education, and
      policy.
AB  - This paper briefly critiques each of four papers presented at the symposium,
      relates how these papers contribute additional information on the realities of
      rural older women, and the implications for future research, policy, and
      outreach. The critique points out that the realities of rural women's lives can
      best be understood through their lens in combination with objective observations.
      Further, most of the conflictual findings in this literature can be attributed to
      a lack of melding of findings across diverse studies. It is concluded that
      effective research, policy, and outreach must be predicated on culturally
      sensitive interpretations of older rural women's realities.

PMID- 9919875
TI  - [Characteristics of paper dust extract in vitro].
AB  - The effects of recycling paper dust extract on isolated nonsensitized guinea pig
      tracheal smooth muscle were studied in vitro. Dust extract was prepared as a 1:10
      w/v aqueous solution. Dose related contractions of guinea pig tracheal rings were
      elicited with paper dust extract. Pharmacologic studies were performed with
      atropine (10(-6) M), indomethacine (10(-6) M), pyrilamine (10(-6) M), Ly 171883
      (10(-5) M), NDGA (10(-5) M) and TMB8 (10(-5) M). The effects of extract were
      almost totally inhibited by the anticholinergic agent atropine, suggesting that a
      principal pathway mediating this response may involve the parasympathetic nervous
      system. The intracellular calcium blocking agent TMB8 also induced a reduction of
      the contractile response to paper dust extract, which is consistent with
      intracellular calcium's well established role in smooth muscle constriction. We
      suggest that paper dust extract causes dose related airway smooth muscle
      constriction, possibly associated with the release of cholinergic as well as
      other mediators. The constrictor effect does not require tissue presensitization.

PMID- 9919876
TI  - [Pneumatization of the middle nasal turbinate: a CT study].
AB  - Anatomic variations of the middle turbinate may be an important factor in the
      pathogenesis of inflammatory processes of the paranasal sinuses. A detailed
      analysis of coronal and axial plane CT scans of the paranasal sinuses obtained
      from 120 patients was performed. Paradoxical curve of the middle concha was
      detected in 24.2% of patients. Pneumatized middle turbinate was found in 42.5%
      and "true" concha bullosa in 8.3% of patients. Bilateral concha bullosa was found
      in 1.7% of patients.

PMID- 9919877
TI  - [The mitral valve prolapse syndrome in children and adolescents].
AB  - The authors studied the prevalence of mitral valve prolapse (MVP) in the group of
      656 children and adolescents (329 males and 327 females), who were a
      representative sample (obtained with the Monte Carlo method of statistical
      trials) of all newborns in the city of Maribor, Republic of Slovenia, in the
      period of 18 years (1976-1992). The results were considered positive in children
      and adolescents who in addition to possible history (chest pain, palpitations,
      dizziness, loss of consciousness, headaches, perspiration), probable auscultatory
      finding (mezzosystolic click and late systolic murmur), and suspected
      phonocardiographic and ECG findings, also had a positive M-mode echocardiographic
      finding. The criteria for MVP on M-mode echocardiography were taken from the
      literature: descending of mitral cusp, either anterior or posterior, of at least
      3 mm below the line connecting points C and D. Children and adolescents were
      divided into six age groups (infants, toddlers, preschool children, early school
      age, children in puberty, adolescents). Assuming MVP as a cause of cardiac
      arrhythmias, beside standard ECG we also performed holter ECG monitoring in 61
      children and adolescents (29 with MVP, 32 without MVP). The results were tested
      with standard statistical tools (chi 2-test, Student t-test, 2 x 2 Fisher chi 2
      test). MVP was found in 71 patients (10.8%, 32 males and 39 females). As regards
      age and sex we found lower prevalence of MVP in male children (9.7%) compared to
      female children (11.9%). The highest prevalence was found in early school age,
      more so in females (14.2 vs 13.7). The differences were not statistically
      significant (p > 0.05). In both sexes most frequent was endosystolic prolapse
      (males 59.3%, females 51.3%). Most commonly both cusps are involved in the
      prolapse (males 78.1%, females 66.7%). Most frequently measured descending of the
      cusps was 3-4.5 mm (males 56.2%, females 48.7%). Negative auscultatory finding
      (silent MVP) was detected in 47.8% of the patients with MVP. Most patients with
      diagnosed MVP had no symptoms (71.8%). The prevalence of asymptomatic MVP
      declines with age in both sexes. The prevalence of arrhythmias, both in standard
      ECG and holter ECG, is higher in patients with MVP (6.8:0%--NS and 44.6%:9.3%--p
      < 0.05). The influence of constitutional changes (dolichostenomelia, asthenic
      constitution, genua valga) on the appearance of MVP is reflected in statistically
      significant difference in the Rohr' index in the group of patients with MVP in
      relation to the healthy group (p < 0.05). The higher prevalence of headache and
      dizziness in the group with MVP is statistically significant (p < 0.05).

PMID- 9919878
TI  - [Turner's syndrome--case report of a female patient with chromosome mosaicism].
AB  - A 45-year old woman with the typical Turner's phenotype (short stature, short and
      broad neck, shield chest and low hairline) and signs of ovarian failure started
      at the age of 37 with menopause at the age of 44, is presented. The cytogenetic
      analysis showed the presence of three different cell lines with 45,X, 46,XX and
      47,XXX karyotypes. It is a rare type of mosaicism, combining Turner's and triple
      X syndrome. Interestingly, the became pregnant and gave birth to a healthy child.
      Second pregnancy resulted in a miscarriage in the first trimester.

PMID- 9919879
TI  - [Sensitivity to latex and other rubber substances--an important occupational risk
      for health personnel (case report)].
AB  - Sensitization to latex and rubber additives has been acknowledged during the last
      10 years as a major occupational health problem among health-care workers. In
      sensitized persons, respiratory and/or skin symptoms may be present.
      Pathophysiologic mechanisms of senzitisation involve allergic reactions types I
      and IV (Coombs and Gell). In this case report we described a female health-care
      worker with sensitization to latex and rubber additives simultaneously present on
      the skin and in the respiratory system, caused by wearing protective rubber
      gloves. The complex diagnostic procedure involved in determination of
      occupational allergic diseases is discussed.

PMID- 9919880
TI  - [Effect of smoking on the feto-placental unit].
AB  - Tobacco smoke and its metabolites, especially nicotine, have an irritant,
      genotoxic, mutagenic, teratogenic, cancerigenic and psychoactive effect. Smoking
      during pregnancy is considered an antepartal (maternal) cause of fetal hypoxemia,
      i.e. fetoplacental respiratory insufficiency. Carboxyhemoglobinaemia and chronic
      hypoxemia, impairment of chorionic histoarchitectonic and placentation,
      vasoconstriction of uteroplacental circulation and intermediary metabolism
      disturbance are the etiopathogenetic basis of intrauterine fetal growth
      retardation, i.e. fetal smoking syndrome.

PMID- 9919881
TI  - [Tumor suppressor genes with special emphasis on the APC tumor suppressor gene].
AB  - Tumor suppressor genes play a central role in the genesis and progression of
      human cancers. Genetic alterations of tumor suppressor genes have been found in a
      variety of hereditary and nonhereditary cancers. Persons that carry a hereditary
      mutation in tumor suppressor genes are strongly predisposed to one or more kinds
      of cancer. This review brings current developments in the field of tumor
      suppressor genes. Special emphasis is dedicated to recently discovered tumor
      suppressor gene APC (adenomatous polyposis coli) whose mutations are responsible
      for familial adenomatous polyposis (FAP). The known mutations of the APC gene are
      described. The role of the APC gene in tumor development, as well as the
      possibility for presymptomatic genetic testing is also discussed in the paper.

PMID- 9919882
TI  - [The cardiovascular system and sports].
AB  - The article deals with the athlete's heart syndrome as well as the views on this
      phenomenon throughout this century. The basic diagnostic procedures for heart
      examination as a part of general medical examination are listed. The authors
      confront the position recommendations of American and European authors for
      determining eligibility for competition in athletes with cardiovascular
      abnormalities.

PMID- 9919883
TI  - [Delusional misidentification syndromes].
AB  - According to ICD-10 and DSM-IV classifications, delusional misidentification
      syndromes are a specific subgroup of unspecified persistent delusional disorders.
      They are characterized by systematic incorrect identification and the basic
      delusional idea--the concept of a double, illusion of a double. The authors
      present the most frequent delusional misidentification syndromes, and the most
      frequent elements of the clinical picture and etiological hypotheses. Because of
      their small frequency and the basic characteristics of these syndromes to appear
      mostly as a part of some other disturbance, the authors emphasize the importance
      of a careful differential diagnostic procedure, which has therapeutic
      implications.

PMID- 9919884
TI  - [Is it necessary to tell the truth to a severely ill patient?].

PMID- 9919885
TI  - Expression of heat shock protein 27 in chromomycosis.
AB  - We report on a 58-year-old woman with long-lasting (36 years) chromomycosis on
      the foot and secondary self-inoculation from foot to hand 4 years ago.
      Mycological classification was performed after culture on Sabouraud glucose agar.
      We used haematoxylin and eosin and Giemsa staining and an antibody to heat shock
      protein (HSP) 27 (Stress Gen, Clone G3.1) on paraffin-embedded and cryostat
      specimens of chromomycosis. The mycological culture revealed the fungus Fonsecaea
      pedosoi. Histopathology revealed dermal fibrosis with persistent fungi (Medlar
      bodies), numerous mast cells and pseudoepitheliomatous hyperplasia.
      Immunohistochemically, HSP 27 was positively identified in F. pedrosoi. Moreover,
      in differentiating keratinocytes in the pseudoepitheliomatous lesions of
      chromomycosis, HSP 27 was increasingly expressed from basal layers to stratum
      spinosum in the epidermis but not in keratinocytes directly bordering Medlar
      bodies. In chromomycosis, HSP 27 is expressed, in accordance with its role as a
      marker of differentiation and proliferation, in keratinocytes and also in F.
      pedrosoi. It remains unknown if these results might explain the therapeutic
      efficacy of hyperthermic treatment.

PMID- 9919886
TI  - AIDS-related visceral aspergillosis: an underdiagnosed disease during life?
AB  - Five out of nine consecutive patients with HIV-related visceral aspergillosis
      observed by us since 1984 were diagnosed only at necropsy examination. The
      histopathological features of these five patients [two with isolated pneumonia,
      one with central nervous system (CNS) involvement, one with brain abscess and
      respiratory disease and one with pulmonary, pleural and kidney infection] have
      been evaluated according to epidemiological, clinical and radiological features.
      On the basis of our experience, life-threatening aspergillosis, which is often
      misdiagnosed or missed in the setting of HIV infection and AIDS, should be
      suspected in patients with far-advanced underlying disease and unexplained signs
      and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia
      and prior steroid treatment). Plain chest radiography and bronchoscopy with
      broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis
      is not necessarily associated with suggestive neuroradiological features and
      disseminated disease may present with multiorgan failure. The unfavorable outcome
      of this emerging AIDS complication can be improved only by earlier diagnosis
      based on invasive techniques and appropriate and timely treatment.

PMID- 9919887
TI  - Reduction in the growth of non-dermatophyte moulds by itraconazole: evaluation by
      corneofungimetry assay.
AB  - The activity of itraconazole against fungi of dermatological importance was
      studied using corneofungimetry performed on four test organisms: Aspergillus
      flavus, Fusarium oxysporum, Scopulariopsis brevicaulis and Scytalidium
      dimidiatum. The human stratum corneum used in the bioassay was harvested from
      healthy volunteers and from patients undergoing treatment with itraconazole 200
      mg daily for at least 2 weeks. A fungal mycelium grew on all untreated stratum
      corneum samples within 1 week. The pattern and extent of growth varied greatly
      among the test organisms. An inhibitory effect was observed on the itraconazole
      treated samples. However, the level of inhibition was higher than that expected
      by calculating itraconazole minimum inhibitory concentrations in a reference
      susceptibility test. It is concluded that some non-dermatophyte moulds of medical
      importance can grow by forming hyphae on human stratum corneum. However, the
      process is partly inhibited by some unknown mechanisms originating from the
      stratum corneum itself. It is further inhibited by the oral administration of
      itraconazole. This global effect might be the result of the complementation
      inhibition due to the drug and/or some unknown components of the stratum corneum.

PMID- 9919888
TI  - Fusarium fungaemia in severely neutropenic patients.
AB  - We report two cases of Fusarium infection with evidence of fungaemia in severely
      neutropenic patients with leukaemia. One patient was a 65-year-old woman with
      chronic lymphocytic leukaemia infected by Fusarium verticillioides. The other
      patient was a 45-year-old woman with acute myeloblastic leukaemia infected by
      Fusarium spp. Fungaemia was the only evident manifestation of these fungal
      infections.

PMID- 9919889
TI  - Efficacy of polymerase chain reaction for detection of deep mycotic infections:
      confirmation by autopsy.
AB  - A method based on polymerase chain reaction (PCR) amplification of fungal 18S
      rDNA sequences was tested for the detection of fungi in blood samples. In order
      to increase sensitivity and specificity, PCR products were hybridized to the
      radioactively labelled fragment of 18S rDNA gene. Blood from 28 patients with
      haematological malignancies was taken immediately after death and the results of
      PCR analysis were compared with results of autopsy examination. To the best of
      our knowledge, no study of such a design has been published previously. PCR
      analysis turned out to be very sensitive (92%) and specific (92%) as well as
      capable of detecting various kinds of fungal infections (localized as well as
      generalized).

PMID- 9919890
TI  - Colorimetric MTT assessment of antifungal activity of D0870 against fluconazole
      resistant Candida albicans.
AB  - The in vitro antifungal activity of D0870 against eight isolates of fluconazole
      resistant Candida albicans was compared with that of itraconazole, ketoconazole
      and miconazole. The colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl
      2H tetrazolium bromide] assay was used to assess the antifungal activities. The
      50% minimum inhibitory concentration (MIC50) of D0870 was below 0.031 microgram
      ml-1 for seven isolates and 0.25 microgram ml-1 for one isolate. The activity of
      D0870 was superior to that of the other azoles. Ketoconazole was the most
      effective azole next to D0870. Therefore, the new bis-triazole, D0870, is
      expected to be promising for the therapy of fluconazole-resistant candidosis. The
      present data also confirmed that the MTT assay may be useful for evaluation of
      resistance and detection of resistant C. albicans.

PMID- 9919891
TI  - Imidazole-induced morphological abnormalities of mitochondria of Candida
      albicans.
AB  - The mitochondrial morphology of live Candida albicans samples treated with
      several imidazoles (miconazole, econazole and clotrimazole) was observed with a
      fluorescent carbocyanine probe, 3,3'-dihexyloxacarbocyanine [diO-C6-(3)], under a
      fluorescence microscope. Nearly all non-treated C. albicans cells carried only
      long tubular mitochondria. Treatment with antimycotics at half the minimum
      inhibitory concentrations (MIC100) rapidly induced mitochondrial cleavage or
      fragmentation, which was followed by recovery to the normal tubular morphology
      within 1 h. Exposing the yeast to drugs at concentrations higher than the MICs
      resulted in the development of swollen mitochondria or amorphous bodies. These
      phenomena were concentration dependent. The fluorescence images were also
      compared with ultrastructural images obtained by transmission electron
      microscopy.

PMID- 9919892
TI  - Comparison of fungal viability assays using Candida albicans yeast cells
      undergoing prolonged incubation in the absence of nutrients.
AB  - Staining methods for determining fungal viability are usually assessed by
      comparisons with enumeration of colony-forming units (CFU) on solid media. The
      purpose of the present study was to compare viability as assessed by the acridine
      orange (AO) and MTT methods with the numbers of CFUs obtained for Candida
      albicans yeast cells undergoing prolonged incubation in distilled water. In
      initial assessments of the assays using various proportions of control and heat
      killed C. albicans, the AO and MTT methods consistently indicated significantly
      higher values for viability than did CFU determinations. Experiments using
      organisms cultured overnight revealed that approximately 95% of the cells were
      capable of dividing at least once in a microscopic proliferation assay, whereas
      only 69% were capable of forming colonies. Parallel assays comparing AO uptake
      and MTT reduction gave excellent agreement with the microscopic proliferation
      assay, but not with CFU determinations. Using organisms undergoing prolonged
      incubations in distilled water, much lower viabilities were obtained with the CFU
      method at 7 and 10 days than with the microscopic proliferation assay or the two
      staining methods. These results indicate that the AO and MTT assays correlate
      well with the ability of C. albicans to divide at least once, but may not
      accurately indicate the percentage of organisms actually able to form colonies.

PMID- 9919893
TI  - Demonstration of Malassezia furfur and M. sympodialis together with M.
      pachydermatis in veterinary specimens.
AB  - In the present study, 47 wild-type isolates of the genus Malassezia were isolated
      from dog and cat specimens by means of a simple differentiating system recently
      published. The purpose was to determine whether any of the other seven Malassezia
      spp. apart from M. pachydermatis occur in carnivores. Of the 47 isolates, three
      had been obtained from cats (ear 2, skin 1) and 44 from dogs (ear 37, skin 3,
      faeces 2, claw and paw 2). After primary isolation, they were subcultured on
      mDixon agar and then purified and differentiated by means of assimilation of
      Cremophor EL, splitting of esculin, growth on lipid-free medium and formation of
      tryptophan-dependent pigments and fluorochromes. Thus, a total of 100 strains
      could be obtained from the 47 primary isolates. Referring to the source material,
      M. pachydermatis was found in 83%, M. furfur in 45% and M. sympodialis in 75%.
      More than 80% of cultures were mixed, comprising two or all three species; a
      single species was isolated in only nine cases. This shows that animals are not
      colonized by M. pachydermatis alone, as has been thought until now, but in nearly
      all cases by mixed cultures. Thus, (domestic) animals could well be a reservoir
      for other Malassezia species such as M. furfur and M. sympodialis. Surprisingly,
      Malassezia yeasts were also isolated from dog faeces, indicating that they
      apparently pass through the gastrointestinal tract in unchanged form after having
      been taken up by licking colonized areas. The survivability of Malassezia yeasts
      in highly acid milieu was also demonstrated in vitro. The study confirms the
      usefulness of the new test procedures and allows new statements concerning the
      epidemiology of Malassezia yeasts.

PMID- 9919894
TI  - Isozyme variation within and among populations of Microsporum species.
AB  - Isozyme variation among 54 isolates of Microsporum canis, 18 Microsporum cookei
      isolates and two Diheterospora isolates were studied using starch gel
      electrophoresis. Of eight enzymes examined, four were polymorphic (EST, G6P, MDH
      and PEP), having from two to four electrophoretic forms. Within each species,
      consistent and reproducible isozyme patterns of the eight enzyme systems were
      obtained. Phenotypic diversity (H) in M. canis was higher than in M. cookei (H =
      0.459 and H = 0.408 respectively), but phenotypic differentiation of M. canis
      isolates from different geographical regions (Auckland, Wellington and Palmerston
      North, New Zealand) was low, with a proportion of total diversity (Gst) of 0.151
      found among the localities. The results suggest that the isolates of M. canis
      from different geographical regions are closely related, supporting the theory of
      a common lineage.

PMID- 9919895
TI  - Itraconazole in the treatment of tinea corporis and tinea cruris: comparison of
      two treatment schedules.
AB  - The efficacy and safety of two dos-ages of itraconazole in the treatment of tinea
      corporis or cruris were compared in a multicentre, randomized, double-blind,
      parallel-group trial. Fifty-four patients received itraconazole 100 mg daily for
      2 weeks and 60 received itraconazole 200 mg daily for 1 week. After a 6-week
      follow-up period, mycological cure was achieved in 70% of patients in the 100
      mg/2 weeks group and in 60% of those in the 200 mg/1 week group (not
      significantly equivalent); in the worst-case and intention-to-treat analyses,
      mycological cure rates (45-49%) were borderline equivalent at the end of follow
      up. Clinical response was seen in 80% of evaluable patients in the 100 mg/2 weeks
      group and in 73% in the 200 mg/1 week group at the end of follow-up (borderline
      equivalent). Similar results were found in the intention-to-treat analysis. The
      tolerability ratings for the two regimens were significantly equivalent. Thirteen
      patients (24%) in the 100 mg/2 weeks group but only nine (15%) in the 200 mg/1
      week group reported adverse events during treatment. Two patients in the 200 mg/1
      week group stopped treatment because of adverse events. No clinically significant
      changes were seen in laboratory parameters in either treatment group. This trial
      showed that itraconazole 200 mg for 1 week is similarly effective, equally well
      tolerated and at least as safe as the established regimen of itraconazole 100 mg
      for 2 weeks in the treatment of tinea corporis or cruris.

PMID- 9919896
TI  - Itraconazole in the treatment of tinea pedis and tinea manuum: comparison of two
      treatment schedules.
AB  - A multicentre, randomized, double-blind, parallel-group trial was conducted to
      compare the efficacy and safety of two dosages of itraconazole in the treatment
      of tinea pedis or manuum. Of the 135 patients recruited, 66 received itraconazole
      400 mg daily for 1 week and 69 received itraconazole 100 mg daily for 4 weeks. In
      the evaluable patients observed-case analysis, mycological cure was seen in 63%
      of patients in the 400 mg/1 week group and in 75% in the 100 mg/4 weeks group at
      the end of a 6-week follow-up period (not significantly equivalent). In the
      evaluable patients worst-case analysis and the intention-to-treat analysis,
      mycological cure rates in the two groups were borderline significantly equivalent
      at the end of follow-up (range 51-57%). Clinical response was seen in 81% of
      evaluable patients in the 400 mg/1 week group and in 75% in the 100 mg/4 weeks
      group at the end of follow-up; equivalence testing showed the 400 mg/1 week
      regimen to be at least equivalent to the 100 mg/4 week regimen. Similar results
      were found in the intention-to-treat analysis, and tolerability ratings for the
      two treatment regimens were significantly equivalent. This trial has shown that
      itraconazole 400 mg/1 week and itraconazole 100 mg/4 weeks are both effective
      regimens for the treatment of tinea pedis or manuum. The two treatment schedules
      were equally well tolerated and safe.

PMID- 9919897
TI  - Safety and efficacy of intermittent therapy with itraconazole in finger- and
      toenail onychomycosis: a multicentre trial.
AB  - The efficacy and safety of intermittent itraconazole therapy were investigated in
      patients with onychomycosis. Patients were divided into two groups according to
      site and extent of infection. Group A comprised 635 patients with toenail
      onychomycosis (at least one nail with > or = 20% involvement; n = 560) or
      fingernail onychomycosis (at least one nail with > 75% involvement; n = 63) or
      both (n = 12). These patients received itraconazole 400 mg day-1 for 1 week per
      month for 3 months. Group B comprised 48 patients with fingernail onychomycosis
      (at least one nail with > or = 20% involvement but no nail with > 75%
      involvement) who received itraconazole 400 mg day-1 for 1 week per month for 2
      months. Patients were followed for a further 18 weeks without treatment, and
      received another treatment cycle if not cured or markedly improved 6 weeks after
      the end of the last cycle. An additional cycle was administered to 76 patients
      with fingernail onychomycosis (group A, n = 43; group B, n = 28) and to 316
      patients with toenail onychomycosis. Clinical response rates and mycological cure
      rates at study end point were 89.0% and 68.4% respectively for toenails, 91.4%
      and 85.3% respectively for group A fingernails and 84.4% and 77.1% respectively
      for group B fingernails. Most adverse events occurred infrequently; major changes
      in liver function tests were not noted. In conclusion, intermittent itraconazole
      therapy is highly effective and safe in patients with onychomycosis.

PMID- 9919898
TI  - Euphorbia hirta leaves and Musa sapientum fruits in culture media for fungi.
AB  - Two plant products, Euphorbia hirta leaves and fruits of Musa sapientum, were
      evaluated as principal ingredients for selective cultivation of fungi. Sapientum
      glucose agar supported the growth of both dermatophytic, yeast-like, and
      saprophytic fungi; growth on this medium compared favourably with growth on
      Sabouraud glucose agar, a standard mycological medium. Sporulation and pigment
      formation were stronger on sapientum glucose agar than on Sabouraud glucose agar,
      although fungal growth on the latter was more luxuriant. Addition of Euphorbia
      extract to mycological media remarkably enhanced fungal growth on the media, and
      concomitantly suppressed bacterial growth to a similar extent as did antibiotics.
      The results of this study suggest that Euphorbia sapientum glucose agar can
      safely be recommended as a cheap and efficient medium for routine isolation of
      fungi in both clinical and general mycological studies.

PMID- 9919899
TI  - Antifungal activity of Indian plant extracts.
AB  - In vitro studies of water extracts of plants such as Terminalia chebula, Punica
      granatum, Delonix regia and Emblica officinalis were found to be detrimental to
      test dermatophytes.

PMID- 9919900
TI  - Quantitative kinetic analysis of blood vessels in the outer membranes of chronic
      subdural hematomas.
AB  - Dynamic biologic modeling was used to calculate the transfer rate constant for
      gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) and capillary
      permeability in the outer membrane of chronic subdural hematomas and effusions.
      Following intravenous Gd-DTPA injection, Gd concentrations in the subdural fluid
      and in timed arterial blood samples were measured by ion-coupled plasma emission
      spectrometry in 53 chronic subdural hematomas and 18 chronic subdural effusions.
      The capillary surface area in outer membrane was assessed morphometrically.
      Transfer rate constants for subdural hematomas and subdural effusions were 12.4
      +/- 1.0 and 20.6 +/- 1.7 (x 10(-4)min-1, respectively. Capillary permeabilities
      for subdural hematomas and subdural effusions were 16 +/- 1.2 and 19 +/- 3.7
      ml.min-1(mm2/mm3)-1, respectively. The capillary surface areas for subdural
      hematomas and subdural effusions were 48 +/- 3 and 77 +/- 10 mm2/mm3,
      respectively. The high degree of infiltration of Gd into subdural effusions
      reflects the high capillary surface area in the outer membrane rather than
      greater permeability of individual capillaries. The value of transfer rate
      constant was correlated inversely with the duration of the chronic subdural fluid
      collection. Immature outer membrane has a high transfer rate constant which
      allows extravasation of plasma components into the subdural space, resulting in
      increasing volume of the subdural effusion. Delayed magnetic resonance imaging
      following Gd administration may be clinically useful for estimating the age of
      chronic subdural fluid accumulations.

PMID- 9919901
TI  - Combination of serine protease inhibitor FUT-175 and thromboxane synthetase
      inhibitor OKY-046 decreases cerebral vasospasm in patients with subarachnoid
      hemorrhage.
AB  - The preventive effect of the serine protease inhibitor FUT-175 (nafamostat
      mesilate), a potent inhibitor of the complement system, against vasospasm was
      evaluated in 34 high risk patients with thick and diffuse subarachnoid hemorrhage
      (SAH) demonstrated by computed tomography corresponding to Fisher group 3. All
      patients underwent surgery within 96 hours following SAH and received the
      thromboxane A2 synthetase inhibitor, OKY-046, as part of standard care. FUT-175
      (40-160 mg/day) was administered during the initial 4 days following surgery. 455
      patients treated without FUT-175 in the Nagasaki SAH Data Bank (non-FUT group)
      formed the control group. FUT-175 significantly decreased the incidence of
      symptomatic vasospasm in patients with severe neurological grade (Hunt and Hess
      grade 3, p < 0.02; Hunt and Hess grade 4, p < 0.02). The incidence of favorable
      outcome was 76.5% in the FUT group and 60.4% in the non-FUT group, but not
      statistically different. However, when patients of Hunt and Hess grade 5 were
      excluded, the FUT group had a significantly improved outcome (p < 0.05). This
      study suggests that FUT-175 has an additive effect to OKY-046 in preventing
      vasospasm in high risk patients with severe SAH.

PMID- 9919902
TI  - Relationship between intracranial pressure and the development of vasospasm after
      aneurysmal subarachnoid hemorrhage.
AB  - The relationship between intracranial pressure (ICP) and the development of
      vasospasm after subarachnoid hemorrhage caused by the rupture of an intracranial
      aneurysm was investigated. Eleven patients were divided into high (6 cases) and
      low (5 cases) ICP groups based on ICP data obtained during the perioperative
      period by continuous ICP monitoring. Transcranial Doppler ultrasonography was
      performed every 24 hours for 7 days and the severity, distribution, and duration
      of vasospasm were assessed. The high ICP group tended to have severe, prolonged,
      and diffuse vasospasm compared with the low ICP group. However, only duration of
      vasospasm was statistically different. The relationship between cerebral
      perfusion pressure (CPP) and the development of vasospasm was also examined. CPP
      had a less significant effect than ICP although similar tendencies for high ICP
      and low CPP were observed. High ICP worsens vasospasm and treatment for
      decreasing ICP with perioperative ICP monitoring has potential for avoiding the
      development of vasospasm.

PMID- 9919903
TI  - Nine cases of nontraumatic spinal epidural hematoma.
AB  - Nontraumatic spinal epidural hematoma (NSEH) is a rare but potentially serious
      spinal disease, which progresses inexorably to a catastrophic neurological
      situation if left untreated. Nine patients (5 males and 4 females, mean age 59.8
      years) with NSEH were admitted to our hospital between 1987 and 1997. Clinical
      data, imaging, and operative results of these patients were analyzed
      retrospectively. Multilaminectomy was performed to decompress the affected
      levels. Postoperative neurological evaluation revealed functional improvement in
      five patients and no significant change in four patients. The most important
      factors influencing postoperative recovery were the preoperative neurological
      condition of the patient and the interval from onset of deficit until the
      operation. Magnetic resonance imaging allows non-invasive and specific diagnosis
      of NSEH, except in the first 24 hours. Computed tomography myelography with
      sagittal reconstructions provides specific diagnosis in this period. Combination
      of these diagnostic imaging modalities allows early diagnosis. Surgical
      decompression within 24 hours of complete sensorimotor deficit or within 48 hours
      of incomplete sensorimotor deficit will achieve the optimum outcome.

PMID- 9919904
TI  - Circulatory arrest with profound hypothermia during the surgical treatment of
      large internal carotid artery aneurysm--case report.
AB  - A 43-year-old male presented with a cerebral aneurysm manifesting as right facial
      paresthesia, without neurological deficit. Angiography revealed a large aneurysm
      (22 mm) of the left internal carotid artery. Intravascular treatment using
      placement of a detachable coil was attempted, but the coil did not stay in the
      aneurysmal cavity and the procedure was abandoned. The patient did not tolerate
      the transient balloon occlusion test of the left internal carotid artery.
      Therefore, the aneurysm was clipped through an open craniotomy with profound
      hypothermia (20 degrees C) with cardiac arrest (24 minutes). The aneurysmal dome
      was collapsed, allowing easy dissection of the posterior communicating artery.
      The closed chest method was used during the extracorporeal cardiopulmonary
      bypass. Postoperative angiography revealed complete neck clipping with
      preservation of carotid blood flow. The patient recovered well and resumed his
      employment. Circulatory arrest with hypothermia provides several benefits for the
      surgical treatment of large and giant aneurysms.

PMID- 9919905
TI  - Angiographic documentation of de novo aneurysm--case report.
AB  - A 49-year-old female presented with a case of de novo aneurysm which was
      documented angiographically 10 years after the initial aneurysm rupture. The de
      novo aneurysm arose as a blister-like aneurysm from a previously normal location
      7 years after the first ictus. The de novo aneurysm progressed to a saccular
      aneurysm and ruptured after another 3 years. We recommend late angiography in
      high-risk patients to prevent repeat ictus.

PMID- 9919906
TI  - Hemangiopericytoma arising at the site of a dural graft 13 years after total
      removal of a benign meningioma--case report.
AB  - A 64-year-old female presented with hemangiopericytoma arising from a dural
      fascia graft placed after a previous operation for the total removal of a benign
      meningioma. The patient also had multiple pulmonary metastases identified as
      hemangiopericytoma. The tumor resected at the first operation was benign based on
      all grading systems for meningiomas. We considered that the tumor was a kind of
      scar tumor. The hemangiopericytoma probably developed from a scar tumor at the
      graft. We emphasize the importance of long-term follow-up for patients who have
      undergone surgery for benign tumors.

PMID- 9919907
TI  - Association of cerebral venous malformation with glioblastoma--case report.
AB  - A 73-year-old male was admitted with right-sided motor weakness and presented
      with a rare association of incidental venous malformation in the right frontal
      lobe and a glioblastoma in the left frontal lobe. Computed tomography and
      magnetic resonance imaging failed to demonstrate typical appearance of venous
      malformation and showed atypical findings surrounding the suspected vascular
      lesion. Angiography was needed to obtain the diagnosis of venous malformation.
      The patient underwent subtotal resection of the glioblastoma and received
      radiation therapy. The venous malformation was followed up conservatively because
      it was asymptomatic. Correct diagnosis of coexisting venous malformation is
      important for the treatment of an associated brain tumor, especially when both
      lesions are closely located.

PMID- 9919908
TI  - Subdural empyema caused by hematogenous dissemination from an abscess in thigh to
      a preexisting chronic subdural hematoma--case report.
AB  - A 63-year-old male with a preexisting chronic subdural hematoma presented with
      progressive confusion and left hemiparesis as well as high fever. Subdural
      empyema was strongly suspected. At surgery, the empyema was encapsulated by
      definite inner and outer membranes. Cultures isolated from the subdural fluid and
      from an abscess of his left thigh yielded methicillin-resistant Staphylococcus
      aureus. A pulsed-field gel electrophoresis showed these two strains were
      genetically identical. Hematogenous infection of a preexisting subdural hematoma
      is an extremely rare cause of subdural empyema.

PMID- 9919909
TI  - Model-based surgical planning and simulation of cranial base surgery.
AB  - Plastic skull models of seven individual patients were fabricated by
      stereolithography from three-dimensional data based on computed tomography bone
      images. Skull models were utilized for neurosurgical planning and simulation in
      the seven patients with cranial base lesions that were difficult to remove.
      Surgical approaches and areas of craniotomy were evaluated using the fabricated
      skull models. In preoperative simulations, hand-made models of the tumors, major
      vessels and nerves were placed in the skull models. Step-by-step simulation of
      surgical procedures was performed using actual surgical tools. The advantages of
      using skull models to plan and simulate cranial base surgery include a better
      understanding of anatomic relationships, preoperative evaluation of the proposed
      procedure, increased understanding by the patient and family, and improved
      educational experiences for residents and other medical staff. The disadvantages
      of using skull models include the time and cost of making the models. The skull
      models provide a more realistic tool that is easier to handle than computer
      graphic images. Surgical simulation using models facilitates difficult cranial
      base surgery and may help reduce surgical complications.

PMID- 9919910
TI  - Transplantation of neural tissue into the brain--a new therapeutic modality for
      the 21st century.

PMID- 9919911
TI  - Gene therapy of central nervous system tumors.
AB  - Recently, remarkable advances have been achieved in molecular and genetic
      researches of different kinds of general diseases, as well as in basic and
      clinical studies using gene therapy for central nervous system diseases. For
      brain tumors, clinical trials have been already started in more than 10 clinical
      protocols and more than 100 patients with malignant brain tumors. Nevertheless,
      there are still major issues that remain to be resolved for achieving better
      clinical results, such as delivery system of genetic material, regulatory methods
      of the intracellular expression of the transgene, antitumor efficacy, and tumor
      selectivity. In this paper, molecular genetic studies and the current state of
      gene therapy for neurological diseases, especially brain tumors, are described,
      and the future direction of this fascinating approach is discussed.

PMID- 9919912
TI  - Application of biomedical engineering to neurosurgery.
AB  - Biomedical engineering is increasingly becoming very important also in
      neurosurgery. This article describes some examples of neurosurgical applications
      of biomaterials which play a central role in biomedical engineering. Since a
      large number of biomaterials are currently used in neurosurgery, only the
      biomaterials that have been developed in our laboratories in collaboration with
      neurosurgeons are briefly presented here. The biomaterials developed include
      devices used for interventional neurosurgery and bioabsorbable scaffolds for
      regeneration of dura mater and skull bone. We developed an immediately
      electrically detachable coil using a poly(vinyl alcohol) junction between the
      coil and the delivery wire. This is the first detachable coil developed in Japan
      and is currently under clinical trial. In addition to the coil used for
      interventional neurosurgery, the development of an embolic liquid is presented.
      As an alternative to allografts such as Lyodura, we developed a dural substitute
      from synthetic bioabsorbable polymers which are completely free from potential
      risk of latent virus infection. Finally, our experience in tissue engineering for
      skull bone regeneration using growth factors coupled with polymeric carriers is
      presented to demonstrate the promise of tissue engineering in the future.

PMID- 9919914
TI  - Application of functional electrical stimulation to the paralyzed extremities.
AB  - This paper describes restoration of motor function in patients with paralyzed
      extremities due to upper motor neuron disorders by functional electrical
      stimulation (FES). Percutaneously indwelling intramuscular electrodes were
      implanted into the muscles of the paralyzed upper and lower extremities to be
      controlled by FES. Stimulation patterns for extremity FES were created from
      electromyography (EMG) during motion in healthy subjects. By using a percutaneous
      FES system, all of the joint movement in the extremities could be controlled as
      long as severe lower motor neuron damage did not exist. In the paralyzed upper
      extremity, motor function of not only the hand but also the wrist, elbow, and
      shoulder could be restored with well-coordinated manner by EMG-based stimulation
      data and utilized for vocational tasks in the hemiplegic and quadriplegic
      patients. Continuous bias stimulation to the paralyzed muscle in combination with
      volitional contraction of its antagonistic muscles provided the patient with more
      volitional and natural control of the upper extremity. Restoration of locomotive
      movement in the paraplegics at around T-8 level was also achieved by FES under
      the usage of a walker.

PMID- 9919913
TI  - Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in
      the treatment of brain and spinal cord tumors.
AB  - The Cyberknife is an image-guided "frameless" dedicated radiosurgical device.
      This instrument has several distinct advantages over frame-based systems,
      including improved patient comfort, increased treatment degrees of freedom, and
      the potential to target extracranial lesions. Clinical results thus far with
      respect to the treatment of malignant intracranial tumors has been promising.
      Additionally, the Cyberknife will likely revolutionize the application of
      radiosurgery to extracranial sites. A description of the components, treatment
      planning, and clinical results of the Cyberknife will be reviewed.

PMID- 9919915
TI  - [The 80th anniversary of the National Institute of Hygiene in Warsaw].

PMID- 9919916
TI  - [Meningococcal infections in Warsaw's district].
AB  - The epidemiological situation of meningococcal meningitis in Warsaw's district in
      comparison to the situation in Poland in the years 1980-1997 in discussed. In
      September 1997, the local population of Zielonka--small city in Warsaw's
      district, was alarmed by two meningococcal septicaemia cases in girls attending
      to the same kindergarten. Anti-epidemic measures undertaken were described.

PMID- 9919917
TI  - [The study of carrier of Neisseria meningitidis performed in Zielonec and
      characteristics of meningogocci isolated from patients at the Wolomin hospital,
      Warsaw district].
AB  - Meningococcal carriage study, performed after N. meningitidis outbreak in
      Zielonka included 130 persons (111 children). No N. meningitidis strain was
      isolated. Phenotype and genotype analysis of 6 meningococcal isolates obtained
      from blood and CSF, showed their heterogeneity with exception of 2 isolates from
      Zielonka's cases of meningococcal sepsis which were identical.

PMID- 9919918
TI  - [Diseases caused by hantaviruses].
AB  - Hantaviruses are RNA viruses that belong to the genus Hantavirus, family
      Bunyaviridae. The main reservoir of hantaviruses are rodents. Humans become
      infected by inhaling particles of dust contaminated with faeces of rodents, that
      are found In Europe and Asia hantaviruses named: Hantaan, Seoul and Dobrava
      Belgrade causing haemorrhagic fever with renal syndrome (HFRS) are prevalent.
      Typical clinical picture of HFRS consists of renal insufficiency (primarily
      anuria and then polyuria with disturbances of water and electrolytic balance),
      hypotension, shock and disseminated intravascular coagulation and fibrynolisis
      (DIC). The mild form of this disease caused by Puumala virus is found in
      Scandinavia. North and South America are the regions where the prevalence of
      viruses: Sin Nombre, Black Creek Canal, Bayou, and New York causing hantavirus
      pulmonary syndrome (HPS) has been noted. In the course of this disease non
      cardiogenic pulmonary oedema requires immediate hospitalisation at intensive care
      ward with artificial ventilation. Mortality in HPS due to hypotension, hypoxia
      and shock ranges up to 40%.

PMID- 9919919
TI  - [Does vaccination protect a child of an HBs Ag carrier mother against HBV
      infection?].
AB  - The aim of the study was to determine the degree of protection provided to the
      children born from HBs antigen carrying mothers, by vaccination administered
      according to the 0-1-2-12 scheme (Engerix B, SmithKline Beecham) as well as the
      level of HBs antibodies after a booster dose given 5 years later. The examination
      was conducted in 52 children. The level of HBs antibodies as well as the
      remaining serological markers of HBV infection were assessed at the age of 6.
      Four to six months after booster dose administration the level of HBs antibodies
      was assesed again. The markers of HBV infection were determined with the IMx
      AUSAB test (Abbott Laboratories). After 5 years from the vaccination, 3 (5.8%)
      children were found infected with HBV; the performed assessment of their immune
      system did not reveal any significant compromise. Values of anti-HBs < 10 mlU/ml
      were found in 4 (8.2%) of 49 infection-free children and low levels (11-100
      mlU/ml) in other 4 (8.2%) children, moderate (101-1000 mlU/ml) in 29 (55.8%), and
      very high (> 1000 mlU/ml) in 9 (17.3%). Four to six weeks after a booster dose,
      only one child did not respond to the vaccination. High levels of anti-HBs
      antibodies were obtained in the rest of the children. In our opinion there is a
      justified need to administer a booster dose 5 years after completing the
      vaccination in the risk group children.

PMID- 9919920
TI  - [Registration of the foodborne diseases in Poland in 1919-1997].
AB  - The aim of this paper was presenting of the history of registration of the
      foodborne and waterborne diseases in Poland, as well as describing of the
      epidemiological situation of these diseases. In the years between the I and II
      World Wars and from 1945 to 1947 enteric fever and bacterial dysentery were most
      often registered. From 1951 began the increasing of the total numbers of cases of
      the viral hepatitis with the peak of diseases in 1964 (about 125,000 cases). The
      years 80s were characterized by the increasing number of cases caused by
      Salmonella of animal's source with the peak in 1988 (about 62,000 cases). In the
      years 90s the decrease of the number of salmonelloses of animal's source
      occurred.

PMID- 9919921
TI  - [Outbreaks of foodborne diseases of bacterial etiology in Poland in 1990-1996].
AB  - The domination of salmonellas of animal's source remains in Poland in 1990-1996
      in outbreaks (from 84.4% to 95.8%), despite the decreasing of the yearly numbers
      of diseases caused by foodborne and waterborne infections and intoxications.
      Participation of the S. enteritidis among salmonellas of animal's source amounted
      from 92.6% to 97.8%. The most cases in the total number of diseases in outbreaks
      occurred after eating of the dishes made from eggs (from 41.8% to 54.9%). Food
      prepared in private homes contributed to the occurrence of the outbreaks to the
      highest degree (from 61.1% to 74.3%). The private homes were also the most
      frequent places of the consumption of those dishes. It results from the
      epidemiological data that raw materials (mainly eggs) coming from private farms
      contributed to the contamination of ready food to a high degree.

PMID- 9919922
TI  - [Pathogenicity and diagnosis of Bacillus anthracis].
AB  - In Poland cutaneous form of anthrax is occurring sporadically. Most of these
      cases were recognized in the eastern part of the country adjacent to the eastern
      border (Lomza region and others). The latest literature on epidemiology,
      diagnosis, prevention and treatment of anthrax is reviewed in order to spread
      modern views on anthrax and to implement changes in the diagnostic methods of
      anthrax in Poland.

PMID- 9919923
TI  - [Toxoplasmosis in families. I. Detection of T. gondii invasion and serological
      appraisal].
AB  - Toxoplasmosis was studied in 102 families, in which index-cases manifested the
      fully symptomatic course of the acquired lymphnodular toxoplasmosis, confirmed by
      presence of IgM and IgG class antibodies (ELISA, Vidas, BioMerieux). The index
      cases (group A) provided a rational index of the acquired invasion or its late
      sequele in other families members. The studies were performed in 388 persons,
      originating from Wielkopolska region, including 102 patients of a group A and 286
      of families members of group B (167 children and 221 adults). In group A patients
      (including 49 children and 53 adults) immunoserological studies detected IgM
      class antibodies in 68.7% of cases and IgG class antibodies in 94.1% patients. In
      286 family members (group B), presence of IgM class antibodies was found in 12.2%
      and IgG class antibodies was found in 55.2% studied persons; clinical pathology
      was noted in 46 patients (16.3%) including 3 pregnant women. The obtained results
      point to the need of complex evaluation of family environments based on analysis
      of serological tests (including estimation of IgM and IgG class antibodies) and
      accompanied by clinical analysis of studied children and adults.

PMID- 9919924
TI  - [Toxoplasmosis in families. II. Clinical analysis].
AB  - Clinical and serological analysis was conducted on 102 families including index
      cases of lymphonodular toxoplasmosis (102 patients-group A) and 286 family
      members (group B). The studies included a total of 388 persons (167 children and
      221 adults), originating mainly from Wielkopolska region (West Poland). The
      lymphonodular form of toxoplasmosis represented the dominating pattern among
      adult cases but among children the clinical pathology pattern was variable: in 14
      out of 49 children (group A) lymphadenopathy was not dominating sign and
      clinically signs and symptoms of central nervous system or organ of vision
      involvement prevailed; in 6 cases clinical pattern pointed to congenital
      toxoplasmosis and in 8 cases it indicated sequele of acquired toxoplasmosis. In
      group B, among 35 children with lymphadenopathy, 7 presented also neurological
      signs/symptoms, in 5 children the pattern suggested acquired neurotoxoplasmosis
      in 2 cases congenital form of toxoplasmosis. In 11 adults of the group,
      lymphonodular form of the disease was diagnosed. In both groups (A and B), the
      pattern lymphonodular toxoplasmosis was detected also in 5 pregnant women (1.3%
      of studied persons and 2.7% of all adults). Four of the pregnant women manifested
      active stage of the disease, confirmed by the presence of IgM class antibodies.
      Thus, among 286 family members clinical pathology was demonstrated in 46 patients
      (16.1%) and in 35 patients (12.2%) activity of the disease presented indications
      for a specialistic therapy.

PMID- 9919925
TI  - [Frequency of giardiasis in children with chronic abdominal pain coming from
      North-East Poland].
AB  - Chronic or recurrent abdominal pain constitutes a serious diagnostic and
      therapeutic problem in childhood. The gastrointestinal, biliary tract or renal
      lesions often produce the chronic abdominal pain in children. Among causative
      factors of the chronic abdominal pain the infection with Giardia lamblia is more
      and more often taken into account. The sample of 112 patients hospitalized during
      the period from 1992 to 1993 in two departments of the University School of
      Medicine in Bialystok and in three pediatric wards of the Municipal Hospital in
      Bialystok, was assessed. In all children the duodenal aspiration was performed.
      The following questions were evaluated: 1. What is the frequency of giardiasis in
      children coming from north-east Poland and presenting chronic abdominal pain? 2.
      Is there any specific spectrum of symptoms of giardiasis in children? Based on
      the results of the duodenal fluid examination, the infection with G. lamblia was
      diagnosed in 77 (67.75%) children. The analysis of the clinical symptoms
      indicated that only failure to thrive and recurrent episodes of the loose stools
      were significantly more frequent in infected children compared with uninfected.
      The frequency of the other symptoms like nausea, headache, vomiting,
      constipation, fever or allergic skin lesions was similar in both study groups.

PMID- 9919926
TI  - [A case of meningitis and uveitis caused by Spirochetes of the genus Leptospira].
AB  - A case of meningitis and uveitis caused by spirochetes of the genus leptospira is
      reported in 21 year old man.

PMID- 9919927
TI  - [Criteria and problems related to the diagnosis of malaria, amebiasis and
      leishmaniasis as occupational disease in Polish citizens].
AB  - The general criteria and rules of the current and retrospective diagnosis of
      malaria, amebosis and leishmaniosis were analysed. According to the list of
      occupational diseases the above mentioned infectious diseases are considered as
      occupationally related if they concern Polish citizens who work abroad. The risk
      of infection, the permanent sequelae, the resulting incapacity and the evaluation
      of the claims for health damages are examined. The significance of the problem is
      to be indicated due to the increasing number of Polish citizens exposed
      professionally to the risk.

PMID- 9919928
TI  - [Chronic respiratory symptoms and lung function in children related to air
      pollution in the residential areas].
AB  - The main purpose of the paper was to answer the question whether the various
      respiratory symptoms are related to type of air pollution in the residential
      areas and to which extent the worse lung function in children could have been
      explained by the air pollutants. Cross-sectional field study has been carried out
      in 1048 children aged 11 years attending grammar schools in Krakow. The results
      of the study provided the evidence that the current level of communal air
      pollutants (SPM and SO2) is not related to an excessive risk of respiratory
      symptoms in children, provided it is not combined with other sources of air
      pollution such as heavy traffic or local low point industrial emission. The risk
      of obstructive ventilation disorders (FEV1/FVC% 85) was significantly higher in
      children from the residential areas with higher air pollution (RR = 1.71; 95% CI:
      1.19-2.47).

PMID- 9919929
TI  - [Does exposure to cigarette smoke influence girls maturation?].
AB  - A study of of 26008 school-girls in three biggest cities of Upper Silesia,
      revealed that 76% of the girls were passively exposed to tobacco smoke by their
      smoking parents. In the present paper it is shown that the age at menarche of the
      daughters of smoking mothers is lower than the age at menarche of daughters of
      mothers who do not smoke. This effect appears to be independent of the girl's
      family size, economic situation of the family or parental education. Similar
      influence of smoking father on the menarcheal age of the daughters could be
      detected only in groups of families with high SES.

PMID- 9919930
TI  - [The 50th anniversary of the World Health Organization].
AB  - In the 1998, the World Health Organization celebrates its 50th anniversary. The
      creation of the WHO in 1948 has terminated long-lasting efforts in the
      development of the international organization which can promote, support and
      coordinate improvement in the international health. In the paper, the history of
      the WHO, its present structure and functions, budget, main areas of activity,
      achievements and problems are discussed. The WHO's contribution in the
      improvements in the world's public health and especially in the control of
      infectious diseases is essential. However, to meet new challenges of the coming
      XXI century, and to catalyse, encourage and support needed reforms, the WHO
      itself has to reorganize its structure and to discuss its strategical concepts.

PMID- 9919931
TI  - [Comparative analysis of Bordetella pertussis strains isolated from patients in
      years 1995-1998 and in 1968].

PMID- 9919932
TI  - Living longer. Series looks at how to stay healthy as you age.

PMID- 9919934
TI  - New drug is available to treat Crohn's disease.

PMID- 9919933
TI  - Health tips. Getting 200 minutes of exercise a week.

PMID- 9919937
TI  - Overactive thyroid. Is your thyroid 'hyper'?

PMID- 9919936
TI  - Canes, walkers and crutches. Don't let choosing one throw you off balance.

PMID- 9919935
TI  - Rheumatoid arthritis drugs show promise.

PMID- 9919938
TI  - Fat in your diet. How low should you go?

PMID- 9919939
TI  - I sometimes develop a bump below my kneecap after scrubbing floors. My neighbor
      calls it "housemaid's knee." What is this?

PMID- 9919940
TI  - Cord Blood Transplantation Study Standard Operating Procedures: an evolving
      document will improve cord blood unit quality.

PMID- 9919941
TI  - Ex vivo expansion and differentiation of unselected peripheral blood progenitor
      cells in serum-free media.
AB  - The ability to expand and differentiate unselected PBPC was investigated. Cells
      were grown in serum-free media containing stem cell factor, GCSF and
      megakaryocyte growth and development factor (pegylated PEG-rHuMGDF) with or
      without supplemental serum. Optimal proliferation occurred when PBPC were
      cultured without prior Ficoll-Paque separation in serum-free media. Cell yields
      after 17 days of culture were proportional to the percentage of CD34+ cells in
      the starting population and were 1170+/-302-fold higher than the starting numbers
      of CD34+ cells. Granulocyte-macrophage colony-forming units increased over 12
      days of culture, whereas the numbers of erythroid colony-forming cells peaked
      between 4 and 7 days. Elimination of PEG-rHuMGDF from cell cultures resulted in
      significantly lower yields of myeloid and erythroid colony-forming cells and
      total cell numbers. Cell differentiation into neutrophils was indicated by
      progressive increases in CD11b, CD15, and CD66b expression. Expanded neutrophils
      phagocytosed and killed bacteria as efficiently as neutrophils from normal
      donors. Large-scale expansion studies yielded similar proliferation and
      differentiation results as parallel small-scale cultures. Therefore, unselected
      PBPC can be efficiently expanded and differentiated into large numbers of
      functional mature neutrophils.

PMID- 9919942
TI  - Continuous monitoring of hematocrit values during apheresis for allogeneic
      peripheral blood stem cell collection.
AB  - Rapid changes in the circulating blood volume or hemoglobin level during
      apheresis may pose a risk for healthy individuals donating allogeneic PBSC. In
      this study, a real-time noninvasive monitor CRIT-LINE was used for continuous
      monitoring of hematocrit values in a total of 16 aphereses performed in 4 adult
      (median age 30 years) and 4 pediatric donors (4 years). Donors received
      recombinant G-CSF (10 microg/kg s.c. for 5 days) for mobilization of PBSC. A
      CS3000 plus blood cell separator (Baxter) was used in two different procedures.
      Adults donors were subjected to modified program 1-120 using a combination of the
      granulocyte chamber and the small volume collection chamber (SVCC), and pediatric
      donors were subjected to specialized program 4 with a combination of the newly
      developed small volume separation chamber holder (SVSCH) and SVCC. In all of the
      procedures for children, the extracorporeal line was primed with 400 ml leukocyte
      depleted allogeneic RBC or 200 ml autologous RBC after regular priming with
      normal saline, whereas none of the adult donors received this treatment. We found
      a marked contrast in the hematocrit kinetics during apheresis in the two
      cohorts/procedures. In adults, the initiation of apheresis was followed by an
      immediate decline in the hematocrit value over the initial 10 min until a stable
      plateau level was reached (7% decrease). In children, the values decreased slowly
      but progressively throughout the entire procedure to finally reach a 9% decrease
      at the completion of apheresis. These data may suggest that the use of SVSCH plus
      SVCC or priming with RBC can eliminate the abrupt decline in blood hemoglobin
      levels that occurs during apheresis.

PMID- 9919943
TI  - Minimization of CD34+ cell enumeration variability using the ProCOUNT
      standardized methodology.
AB  - The dose of cells expressing the surface antigen CD34 (CD34+) has been shown to
      be a reliable predictor of the time to engraftment following transplantation of
      PBPC to support high-dose chemotherapy. However, evaluation of rare cells is
      complicated by a number of factors, including the variability in operator and
      technical procedures. Recently, Becton Dickinson Immunocytometry Systems
      introduced a new CD34+ cell analysis system, the ProCOUNT cell enumeration kit,
      which automates the analysis of CD34+ cells and minimizes the variabilities of
      this procedure. We have evaluated the ProCOUNT system in comparison to a standard
      CD34 cell analysis (based on the Milan approach) using leukapheresis products
      from patients and normal donors mobilized with chemotherapy plus recombinant
      human G-CSF (rhG-CSF) or with rhG-CSF alone. In addition, we compared these
      analyses using CD34+ cell-selected mobilized leukapheresis products with purities
      of 75% or greater. The standard CD34 cell analysis methodology quantitated the
      frequency of cells identified as CD45+, low side scatter, and CD34+. A high
      correlation coefficient was obtained between the ProCOUNT methodology and the
      standard CD34 cell analysis methodology for cells obtained from leukapheresis
      products mobilized with chemotherapy plus rhG-CSF (r = 0.98), rhG-CSF alone (r =
      0.96), and CD34+-selected mobilized leukapheresis products (r = 0.83). A
      comparison was also made between technicians using both analysis methods. Whereas
      the correlation coefficient between two technicians using the standard
      methodology was r = 0.77, the correlation coefficient was much higher when using
      ProCOUNT (r = 0.99). These data demonstrate that the use of ProCOUNT is
      associated with less variability between data analyzed by different operators.
      Also, ProCOUNT is consistent with existing CD34+ cellular analysis methodologies.
      An additional advantage is the ability to determine the absolute concentration of
      CD34+ cells, thereby allowing calculation of total CD34+ cell numbers without
      using WBC counts, which also have inherent errors. The ProCOUNT system provides
      an automated analysis procedure that minimizes the variables in CD34+ cell
      analysis and may be useful for standardization of methodology between
      laboratories.

PMID- 9919944
TI  - Mobilization and transduction of peripheral blood progenitor cells in patients
      with mucopolysaccharidosis I.
AB  - Mucopolysaccharidosis type I (MPS I) results from a deficiency of alpha-L
      iduronidase enzyme (IDUA), an enzyme responsible for the catabolism of
      glycosaminoglycans. Genetically modified progenitor cells may permit a
      therapeutic effect similar to that obtained from allogeneic BMT without the
      associated risks. To that end, CD34+ peripheral blood hematopoietic progenitor
      cells from patients with MPS I were mobilized using G-CSF, collected by
      apheresis, and enriched using avidin-biotin separation techniques. These cells
      were cultured in a hollow fiber bioreactor and transduced with a retroviral
      vector (LP1CD) containing the cDNA for human IDUA and a murine dihydrofolate
      reductase (DHFR) enzyme. Approximately 4%-16% of the colonies expressed
      methotrexate drug resistance. Expression of the IDUA enzyme in the progenitor
      cells was initially high and declined after approximately 10 days of culture.
      These results indicate that PBPC from patients with MPS I can be mobilized,
      isolated, enriched, and transduced with a therapeutic gene.

PMID- 9919945
TI  - Homeobox genes and hematopoiesis: an emerging picture for genomic therapy.

PMID- 9919947
TI  - Robustness testing of a liquid chromatography method for the determination of
      vorozole and its related compounds in oral tablets.
AB  - The robustness of a method for the determination of vorozole in oral tablets was
      examined by applying a two-level, seven factor Plackett-Burman statistical
      experimental design. Five method variables that are sensitive to variation,
      especially during method transfer, were evaluated for their influence on the
      system suitability criteria set in the method procedure and on the analysis time.
      The method variables were investigated in a specified range above and below the
      nominal method conditions. They included the concentration of an ion-pairing
      agent, the percentage organic modifier at the start of the linear gradient, the
      mobile phase flow rate, the percentage organic modifier at the end of the linear
      gradient and the pH of the mobile phase. Two dummy factors were included in the
      design to estimate the experimental error. It was found that none of the five
      studied variables affected significantly (t-test, alpha = 0.01) the capacity
      factor, the tailing factor or the analysis time. The resolution of the critical
      peak pair on the other hand, was significantly influenced by the factor pH.
      However, the responses for the resolution of all the experimental runs in the
      design were well above the system suitability limit stated in the normal assay
      procedure. Therefore, the method can overall be considered robust.

PMID- 9919946
TI  - Cord Blood Transplantation Study (COBLT): cord blood bank standard operating
      procedures.
AB  - In 1995, the National Heart Lung and Blood Institute (NHLBI) solicited requests
      for a proposal (RFP) entitled "Transplant Centers for Clinical Research on
      Transplantation of Umbilical Cord Stem and Progenitor Cells." Three banks, six
      transplant centers, and one medical coordinating center (MCC) (Table 1) were
      funded with the overall goal of banking cord blood units (CBU) using a single
      manual of operations. Furthermore, the clinical protocols to evaluate the
      transplant outcome for adult and pediatric recipients of these well-characterized
      CBU would be analyzed in a uniform fashion. Because of the intense interest of
      the transplantation community in the policies and procedures for cord blood
      collection and processing, the principal investigators of the cord blood banks
      (CBB) and NHLBI elected to submit for publication the rationale and an abridged,
      but detailed, version of the standard operating procedures (SOP) developed
      between October 1996 and July 1998 prior to the initiation of the clinical
      protocols to be performed with these CBU. As the SOP will be refined over time,
      the complete SOP and subsequent amendments will be published and continually
      updated on the websites from the MCC-The EMMES Corporation (www.EMMES.com). All
      forms referred to in this document may be obtained from the EMMES website. It is
      hoped that the publication of this document will lay down a framework that will
      not only facilitate the development of other CBB but also help us more rapidly
      define what constitutes an "acceptable" CBU product.

PMID- 9919948
TI  - Uniformity of dosage units--comparative study of methods and specifications
      between Eur. Pharm. 3rd and USP 23.
AB  - Methods and specifications of Eur. Ph. 3rd Ed. and USP 23 for the evaluation of
      the uniformity of dosage units were compared, in relation to: (i) allowed
      dispersion of the sample; and (ii) adequability to control the individual
      contents of active ingredient in relation to the labelled amount. Using the
      characteristics of the normal distribution curve, we calculate: (1) the highest
      dispersion allowable, represented by the relative standard deviation of the
      uniformity of mass of single-dose preparations of Eur. Ph. 3rd Ed., (results were
      3.4, 5.1 and 6.8% for L1 = 5, L = 7.5 and L = 10, respectively); and (2) for all
      the methods studied the allowable units frequency for different intervals of the
      labelled amount. Differences between the tests of Eur. Ph. 3rd Ed. and USP 23 can
      lead to acceptance samples with very different individual contents variability,
      namely if the limit specifications for the strength was +/- 10%. The main reasons
      for that are: (1) in Eur. Ph. 3rd Ed., the limits are set with reference to the
      average content of the sample, and in USP 23, they are set with reference to the
      labelled amount of the active ingredient; and (2), the USP 23 calculates the
      content of active ingredient in each tablet from the result of the assay, when
      the weight variation method was used. Taking +/- 5% of label claim as the
      specification for the strength of the product, according EEC requirements, the
      maximum percentage of units outside the range 95-105% of label claim allowed by
      Eur. Ph. 3rd Ed. and USP 23 tests are similar.

PMID- 9919949
TI  - Effect of molecular parameters on the retention of steroid drugs on alumina
      support.
AB  - The retention of 18 steroids was determined on an alumina HPLC column and in TLC
      carried out on alumina layers using dichloroethane-dioxane mixtures as eluents.
      R(M0)-values of steroids decreased linearly with increasing concentration of
      dioxane in the eluent. The adsorption capacity and specific hydrophilic surface
      area of steroids were not correlated indicating the inhomogenous character of
      steroids as solutes. The prediction power of TLC for HPLC was low probably due to
      the different pH of alumina surface. The hydrogen donor and hydrogen acceptor
      capacities of steroids have the highest impact on the retention. Steroids with
      free -OH group differ in their retention behavior from the other derivatives.

PMID- 9919950
TI  - Relationship between retention characteristics and physicochemical parameters of
      solutes on porous graphitized carbon column.
AB  - The retention of 44 barbituric acid derivatives was determined on porous
      graphitized carbon (PGC) column using dioxane water mixtures as eluents. Linear
      correlations were calculated between the logarithm of the capacity factor and the
      dioxane concentration in the eluent. Free Wilson analysis combined with stepwise
      regression analysis was used to elucidate the role of individual substituents in
      the retention behaviour. Calculations indicated that the apolar substituents lie
      parallel to the surface of PGC surface increasing in this manner the retention
      and--as opposed to the retention characteristics of traditional reversed-phase
      supports--the position of substituents also exerts a marked influence on the
      retention.

PMID- 9919951
TI  - Estimation of impurity profiles of drugs and related materials: part 19: theme
      with variations. Identification of impurities in 3-oxosteroids.
AB  - Due to the varied reactions leading to the 3-oxo group in steroids and the
      reactivity of its environment, a large number of impurities related to this group
      are formed during the reaction steps and the degradation studies. In this paper
      the experiences from the authors laboratory with the 3-oxo-related impurities in
      19-nor-4-ene-3-oxosteroids (norgestrel, norethisterone, nandrolone, its esters
      and Nestorone) as well as corticosteroids (prednisolone, mazipredone, etc) are
      presented. The impurities include saturated 3-ones, 1-ene-3-ones, 5(10)-ene-3
      ones, 3-deoxo and 3-ethinyl-3,5-diene derivatives, 6-ene, 8(14)-ene, 6,8(14)
      diene, 6-hydroxy (alpha and beta), 10beta-hydroxy and 6-one derivatives in 4-ene
      3-oxosteroids and 8(9)-ene, 9(11)-ene, 11alpha-hydroxy, 11-oxo and 4-ene-3-one
      derivatives in 11beta-hydroxy-1,4-diene-3-oxosteroids. The chromatographic,
      spectroscopic and hyphenated techniques used in this study include TLC, GC, HPLC
      with diode array UV detector, GC-MS, LC-MS and NMR methods.

PMID- 9919953
TI  - Electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole derivatives
      using carbon paste electrodes.
AB  - The electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole
      derivatives was made by cyclic and linear sweep voltammetry using a carbon paste
      electrode (CPE, graphite/solid paraffin ratio 2:1) as working electrode and an
      Ag/AgCl reference electrode. The current-potential curves were recorded in anodic
      polarisation in -0.1 and +1.3 V range using aqueous solutions and different
      buffers (between pH 1.2 and 10.0), with 20 or 50 mV s(-1) sweep rate. The
      oxidation peak appears between +0.65 and +0.70 V due to disulphides formation.
      The 5-phenyl derivative has two oxidation peaks, the first at +0.45 +/- 0.03 V
      and the second at +0.65 +/- 0.03 V. The oxidation potentials are pH dependent,
      decreasing from 0.9 +/- 0.1 V at pH 1.2 to 0.6 +/- 0.1 V at a pH between 8.0 and
      10.0. In some potential ranges depending on pKa of molecules the oxidation
      potential and oxidation current are pH independent. Simple, precise and accurate
      voltammetric methods for the determination of these compounds were developed and
      validated in 2.5 x 10(-6)-7.5 x 10(-4) mol l(-1) concentration ranges. The
      detection limits were 2.3 micromol l(-1) for 5-ammino-, 12.3 micromol l(-1) for 5
      acetylammino-, 11.6 micromol l(-1) for 5-allylammino-, and 1.2 micromol l(-1) for
      5-phenylammino-2-mercapto-1,3,4 thiadiazole derivatives.

PMID- 9919952
TI  - Tetracycline, oxytetracycline and chlortetracycline determination by flow
      injection potentiometry.
AB  - This paper describes tetracycline (TCH), oxytetracycline (OTCH) and
      chlortetracycline (CTCH) determination by flow injection potentiometry. In the
      flow system proposed TC samples are inserted in a carrier solution and converged
      with a Cu(II) solution of known concentration; the Cu(II) decrease due to its
      complexation with tetracyclines (TC) was monitored. The detector used was a
      homogeneous crystalline CuS/Ag2S double membrane tubular electrode with increased
      sensitivity. The present system allows tetracyclines determinations within a 48.1
      4.8 x 10(3) ppm for TCH, 49.1-4.9 x 10(3) ppm for OTCH and 51.5-5.1 x 10(3) ppm
      for CTCH and a precision better than 0.4% for the three TC species. This
      procedure accomplishes 150-200 samples h(-1) with a Cu(II) consumption of about
      13 microg determination(-1).

PMID- 9919954
TI  - A rapid and sensitive procedure for the micro-purification and subsequent
      characterization of peptides and protein samples by N-terminal sequencing and
      matrix assisted laser desorption ionization time of flight mass spectrometry.
AB  - The characterization of the proteome, a key activity in the post-genome era, is
      made extremely challenging by the microheterogeneity introduced by post
      translational modifications such as glycosylation in the diverse set of proteins
      expressed in a cellular system. High resolution separation systems, such as 2D
      gel electrophoresis and more recently liquid chromatography (LC) have been used
      to fractionate these complex mixtures, however, subsequent mass analysis is
      hindered by the low level of the purified components. Off-line coupling of matrix
      assisted laser desorption ionization time of flight mass spectrometry (MALDI
      TOF/MS) is an attractive technique for the analysis of such samples, but suffers
      from sensitivity to the degree of salt contamination that is unavoidable in the
      isolation of low level protein samples from biological extracts. In this
      publication we will report on a novel application of a commercially available
      system for the micro-purification of peptides and proteins. In this procedure
      micro-columns (normally used for sequencing of electroblotted samples) were used
      to rapidly purify protein digests or crude extracts of proteins in sufficient
      amounts for further analyses by protein sequencing and MALDI-TOF/MS. To
      demonstrate the applicability of these techniques we isolated and performed
      structural analysis of the following samples: a high-mannose glycopeptide
      isolated from a digest of the glycoprotein rt-PA, a poly-His tagged recombinant
      DNA-binding protein isolated by Ni2+-chelating agarose and a polyclonal antibody
      sample.

PMID- 9919955
TI  - Chemiluminescence imaging in bioanalysis.
AB  - The development, analytical performance and applications of chemiluminescence
      imaging as a tool for quantitative analyte localization in target biological
      specimens are described. The detection of acetylcholinesterase activity both in
      array format and on a target surface are described. A proposed application of the
      method is a 384 well microtiter format assay for high throughput screening of
      acetylcholinesterase inhibitors such as tacrine, a drug widely used in the
      treatment of Alzheimer's disease, and two recently developed analogues. The
      chemiluminescent system in conjunction with optical microscopy allowed
      localization of acetylcholinesterase in brain tissue sections. We also describe
      the chemiluminescent immunohistochemical localization of interleukin 8 in
      Helicobacter pylori infected gastric mucosa cryosections and an in situ
      hybridization assay for the detection of herpes simplex virus DNA in single
      cells.

PMID- 9919956
TI  - Modification of fluorescent properties of norfloxacin in the presence of certain
      antacids.
AB  - Modification of the fluorescent properties of norfloxacin samples in the presence
      of different antacids in terms of dissolution rates has been reported in a
      previous paper. The formation of chelates with Al3+ and Mg2+ ions has been
      previously suggested as a mechanism of interaction. In the present paper, the
      chelation was studied with different types and amounts of antacids and the
      stability of the non-absorbable chelates with each antacid was studied. Six dose
      fractions of each antacid were used in samples with the same norfloxacin
      concentration (9 microg ml(-1)). All samples were measured using both UV/Vis
      spectrophotometry and spectrofluorimetry, and compared to a standard solution of
      norfloxacin (10 microg ml(-1)) without antacids, used as a reference in the
      calibration of the spectrofluorimeter. The results showed that the fluorescence
      signal features remarkable differences depending on the kind and the
      concentration of antacid, as well as on the time of contact. It was found that
      increasing amounts of antacids increased the fluorescence signal of norfloxacin
      samples. The evolution of the fluorescence signal in function of the antacid
      concentration showed a maximum and a posterior decrease. It was observed that,
      for a higher concentration of antacid in the medium, a higher signal was obtained
      and lower stability of the compound norfloxacin-antacid was observed. The data
      obtained strongly indicated that the binding of Al3+ and Mg2+ ions to the
      carboxylic groups of norfloxacin produced non-absorbable chelates. This effect
      might reduce the drug bioavailability.

PMID- 9919957
TI  - Fluorimetric and solubility studies of nadolol and atenolol in SDS micelles.
AB  - The effect of sodium dodecyl sulfate (SDS) micelles on the spectrofluorimetric
      intensities and on the solubility of two beta-blockers (atenolol and nadolol)
      were studied at 25.0 +/- 0.1 degrees C and I = 0.1 M NaCl. From the dependence of
      these physical properties on SDS concentration it was possible to calculate the
      binding constants drug-micelle, and it was found that both techniques yield
      similar results for the binding constants, and that are in agreement with those
      calculated from the effect of micelles on the apparent acidity constants of the
      beta-blockers.

PMID- 9919958
TI  - Derivative spectrophotometric determination of the triethylammonium salt of
      cefotaxime in presence of related compounds from the synthesis.
AB  - Cefotaxime sodium is a broad spectrum third generation antibiotic. It is obtained
      by reaction of 7-aminocephalosporanic acid (7-ACA) and S-(2-benzothiazolyl)2
      amino-alpha-(methoxyimino)-4-thiazoleethanethio  ate. 2-Mercaptobenzothiazole is
      a by-product of this reaction. A derivative spectrophotometric determination of
      cefotaxime is proposed for its determination in a reaction mixture in the
      presence of the related compounds from synthesis. With this method Beer's law is
      obeyed over a concentration range from 0.005 to 0.080 mg ml(-1) at 276.8 nm (r =
      0.9995). This technique is accurate, precise (RSD = 0.4%), and has a sensitivity
      of 1.2% (differences in analytical response of 0.74 microg ml(-1) could be
      detected). Recovery experiments of cefotaxime from reaction mixtures include 100%
      for all assayed concentrations. For these reasons, this technique is found valid
      for the intended purposes.

PMID- 9919959
TI  - Fluorimetric determination of theophylline in serum by inhibition of bovine
      alkaline phosphatase in AOT based water/in oil microemulsion.
AB  - Theophylline is an effective bronchodilatator used in the treatment of asthma
      which requires frequent control because of its narrow therapeutic index. Over the
      past decade much attention has been dedicated to the peculiar properties of the
      inner water pools of AOT (sodium 2-bishexyl-ethyl sulfosuccinate) microemulsions
      as enzyme microreactors, yet few analytical applications of the latter have been
      reported. We developed an original assay based on the uncompetitive inhibition by
      theophylline of the reaction catalyzed by alkaline phosphatase from bovine liver
      (E.C. 3.1.3.1) of the ELF-97 fluorogenic substrate in borate buffer 20 mM (pH
      8.6)/AOT/iso-octane-ethyl acetate (95:5) at a temperature of 37 degrees C.
      Optimal activity of endogenous plasmatic alkaline phosphatase isoenzymes
      approximately pH 10.5, interfering activity of the serum are avoided. The assay
      is multiple point rate, monitoring the appearance of the photostable fluorescence
      emission of the reaction product (510-530 nm) out of the water pool. The
      influence of several parameters such as the amount of buffer (W(o)), the amount
      of alkaline phosphatase, sample volume (10-30 microl) [corrected], optimal run
      time (1-7 min) and the use of phosphorylating acceptor (2A2MP) are discussed. The
      method was compared to HPLC UV and TDx methods.

PMID- 9919960
TI  - Analysis of lecithin in pharmaceutical products and diet integrators using a new
      biosensor operating directly in non aqueous solvent.
AB  - One of the first examples of a bienzymatic organic phase enzyme electrode (OPEE)
      is described. It was obtained using two enzymes (phospholipase D and choline
      oxidase), both immobilised in kappa-Carrageenan gel and, as electrochemical
      transducer, an amperometric gas diffusion electrode for oxygen. The response of
      the biosensor was recorded and its sensitivity, linearity range, response time
      evaluated. Lastly drugs and diet products containing lecithin were analysed using
      the new biosensor device working in an organic mixture.

PMID- 9919962
TI  - Capillary electrophoretic separation of weak base enantiomers using the single
      isomer heptakis-(2,3-dimethyl-6-sulfato)-beta-cyclodextrin as resolving agent and
      methanol as background electrolyte solvent.
AB  - The sodium salt of the single-isomer, heptakis-(2,3-dimethyl-6-sulfato)-beta
      cyclodextrin (HDMS-betaCD) was used as resolving agent in the capillary
      electrophoretic (CE) separation of weak base enantiomers in pure methanol
      background electrolytes (BEs). According to the requirements of the charged
      resolving agent migration model of CE enantiomer separations (CHARM model), a
      high buffer-capacity, low pH methanolic BE was created from 25 mM phosphoric acid
      and 12.5 mM NaOH. In this BE, the solubility of HDMS-betaCD was as high as 50 mM,
      permitting the realization of very high separation selectivities and short
      separation times for the fully protonated weak base enantiomers.

PMID- 9919961
TI  - Enantiomeric separation of pirlindole by liquid chromatography using different
      types of chiral stationary phases.
AB  - The enantioseparation of pirlindole by liquid chromatography (LC) was
      investigated using three different chiral stationary phases (CSPs) containing
      either cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-R), ovomucoid
      (OVM) or beta-cyclodextrin (beta-CD). The effects of the mobile phase pH on
      retention, enantioselectivity and resolution were studied. Methanol and
      acetonitrile were tested as organic modifiers while the influence of the addition
      to the mobile phase of sodium alkanesulfonates or sodium perchlorate was also
      investigated. Sodium perchlorate was only used on the Chiralcel OD-R column while
      sodium alkanesulfonates were tested as mobile phase additives on the three kinds
      of CSPs. The enantioseparation of pirlindole could be obtained on all CSPs
      tested, the best results with respect to chiral resolution being achieved on the
      Chiralcel OD-R and the OVM columns. The use of sodium octanesulfonate (NaOS) was
      found to improve the enantioseparation of pirlindole on the OVM column while
      enantioselectivity was considerably enhanced by addition of sodium perchlorate on
      the Chiralcel OD-R column.

PMID- 9919963
TI  - Residual solvents determination in pharmaceutical products by GC-HS and GC-MS
      SPME.
AB  - Solid-phase microextraction (SPME) has been applied to the residual solvents
      determination in pharmaceutical products and was compared with the static
      headspace. Three fibers with different polymer films were compared and the
      polydimethylsiloxane/divinylbenzene coated fiber was found to be the most
      sensitive for the analyzed analytes. Between the investigated sample preparation
      techniques, gastight-SPME proved to be the most sensitive, with DL values ranging
      from 5 pg ml(-1) to 2 ng ml(-1). Headspace SPME is more precise, with RSD of peak
      areas values ranging from 2 to 3%. The headspace SPME method was successfully
      validated. The validation data are reported in the text. The most important
      difference between the two techniques is that the gastight SPME showed better
      behavior towards very volatile solvents. Compared with the static headspace
      technique, both SPME methods showed superior results, being compatible with the
      pharmaceutical samples.

PMID- 9919964
TI  - Gas chromatography-mass spectrometric analysis of clenbuterol from urine.
AB  - Clenbuterol which is mostly used as an anabolic agent. It is also used for
      treatment of asthma. Clenbuterol was analysed from urine by using gas
      chromatography-mass spectrometry. GC-MS parameters were determined. Timolol was
      used as an internal standard. Extraction and derivatisation procedure of
      clenbuterol from urine were developed. Clenbuterol was extracted by using
      diethylether/ter-butanol (4:1; v:v) and pH 12 K2CO3/KHCO3 (3:2; w:w) buffer.
      MSTFA/NH4I (1 ml/10 mg) mixture was used for derivatization of clenbuterol.
      Selected ions of clenbuterol-bis-TMS were m/z: 405, 337, 336, 335, 300, and 227.
      Extraction yield and minimum detection limit of clenbuterol from urine were
      identified. Extraction yield was 94.30% and minimum detection was found 0.02 ng
      ml(-1) urine. It has been concluded that the GC-MS method is sensitive, accurate,
      precise, and reproducible for analysing of clenbuterol from urine.

PMID- 9919965
TI  - TLC-UV densitometric and GC-MSD methods for simultaneous quantification of
      morphine and codeine in poppy capsules.
AB  - Thin-layer chromatographic (TLC)-UV densitometric and gas-chromatographic-mass
      spectrometric detection (GC-MSD) methods were developed for simultaneous
      quantification of morphine and codeine in poppy capsules (Papaver somniferum).
      Morphine and codeine were isolated by extraction with chloroform: isopropanol
      (3:1, v/v) at pH = 8.5 and by solid-phase extraction on Snap-Cap cartridges at pH
      = 8.5. The TLC-UV densitometric quantification was performed by external standard
      method on silica gel plates using ethyl acetate: toluene: methanol: ammonia
      (68:17:10:5, v/v) as developing solvent and UV detection at 275 nm. For the GC
      MSD analysis, the drugs were derivatized with acetic anhydride: pyridine (1:1,
      v/v) and separated on a 30 m HP5 capillary column. The quantification was
      performed using nalorphine as internal standard.

PMID- 9919966
TI  - Essential oils analysis. I. Evaluation of essential oils composition using both
      GC and MS fingerprints.
AB  - The chemical nature of essential oils makes them suitable for analysis using a
      gas chromatography-mass selective detector (GC-MSD). Mass spectra (MS) libraries
      can not be used as unique and absolute criteria for the identification of
      chromatogram peaks. The wide variety of MS of the libraries, recorded in
      different conditions, can lead us to erroneous results. In order to increase the
      reliability of the analytical results, we used as identity criteria, both GC
      fingerprints resulted from the relative retention indices (RRI) and the recorded
      MS of the separated compounds. The two criteria have been quantified by their
      correlation with the standards. A new parameter called global composition
      evaluation index (I(GCMS)), which resulted from a well-balanced average of the
      two criteria, has been defined. Because the comparison of the results of the MS
      with databases is more accurate than the RRI, we considered that the ratio of the
      two criteria must be at least GC:MS 1:2. A database containing RRI of about 600
      components, widely found in essential oils composition and separated on HP-5
      column, was created. Two macros based on the Microsoft Excel spreadsheet were
      also created. The program offers the best 20 matches of each compound with the
      combined MS and RRI library. The composition of Romanian Acorus calamus L.
      essential oil was established and the results were compared with those obtained
      by 'classical' methods.

PMID- 9919967
TI  - An accurate stable isotope dilution gas chromatographic-mass spectrometric
      approach to the diagnosis of guanidinoacetate methyltransferase deficiency.
AB  - A gas chromatography-mass spectrometry (GC-MS) method is described for the
      quantification of guanidinoacetate in different body fluids, using a two step
      derivatisation procedure which involves a reaction with hexafluoroacetylacetone
      to form a bis(trifluoromethyl)pyrimidine ring structure followed by a reaction
      with pentafluorobenzyl bromide. 13C2-labelled guanidinoacetate is used as an
      internal standard. Bis(trifluoromethyl)pyrimidine pentafluorobenzyl derivatives
      were separated on a polar capillary GC-column and were quantified using negative
      chemical ionisation mass fragmentography. The detection limit of the method is 1
      pmol guanidinoacetate in a 100 microl sample. Control values were obtained for
      urine (53.9 +/- 25.9 mmol mol(-1) creatinine), plasma (1.08 +/- 0.31 micromol l(
      1)), cerebrospinal fluid (CSF) (0.114 +/- 0.068 micromol l(-1)) and amniotic
      fluid (3.44 +/- 0.64 micromol l(-1)). The applicability of the method is
      illustrated by the determination of guanidinoacetate in urine, plasma and CSF of
      a patient affected with guanidinoacetate methyltransferase deficiency. In all
      body fluids of this patient, guanidinoacetate was highly elevated.

PMID- 9919968
TI  - Determination of benzodiazepines in human urine and plasma with solvent modified
      solid phase micro extraction and gas chromatography; rationalisation of method
      development using experimental design strategies.
AB  - Solid phase micro extraction (SPME) and gas chromatographic analysis was used for
      the analysis of several benzodiazepines (oxazepam, diazepam, nordiazepam,
      flunitrazepam and alprazolam) in human urine and plasma. Several factors likely
      to affect the analyte recovery were screened in a fractional factorial design in
      order to examine their effect on the extraction recovery. Parameters found
      significant in the screening were further investigated with the use of response
      surface methodology. The final conditions for extraction of benzodiazepines were
      as follows: Octanol was immobilised on a polyacrylate fibre for 4 min. The fibre
      was placed in the sample and extraction took place at pH 6.0 for 15 min. Urine
      samples were added to 0.3 g ml(-1) sodium chloride. In plasma, the extraction
      recovery was less than in urine and releasing the benzodiazepines from plasma
      proteins followed by protein precipitation was found necessary prior to sampling.
      The method was validated and found linear over the range of samples. The limits
      of detection in urine were determined to be in the range 0.01-0.45 micromol l(
      1). The corresponding limits of detection in plasma were in the range 0.01-0.48
      micromol l(-1). Finally, the method developed was applied to determine some
      benzodiazepines after administration of a single dose. This method offers
      sufficient enrichment for bioanalysis after a single dose of high dose
      benzodiazepines as diazepam, but for low dose benzodiazepines as flunitrazepam,
      further sensitivity is needed.

PMID- 9919969
TI  - Comparison of different immunoassays and GC-MS screening of benzodiazepines in
      urine.
AB  - A total of 53 urine samples were tested by different immunoassay methods and by
      gas chromatography/mass spectrometry to determine repeatability of the different
      methods and to assess whether the immunoassays performed on samples obtained from
      elderly patients of the emergency section could be considered as reliable enough
      for identifying a benzodiazepine consumption. Repeatability was excellent for
      GC/MS and good for immunoassays. The specificity was not different for the three
      immunoassays (96%). The sensitivity varied from 36, 64 to 75% for OnLine, RIA
      Immunalysis and RIA DPC, respectively. An other difference between immunoassays
      and GC/MS was the ability of GC/MS to detect lorazepam and low concentrations of
      benzodiazepines whereas immunoassays did not.

PMID- 9919970
TI  - Analysis of gentamicin by liquid chromatography with pulsed electrochemical
      detection.
AB  - The analysis of gentamicin by liquid chromatography using a column packed with
      poly(styrene-divinylbenzene) and pulsed electrochemical detection on a gold
      electrode is described. The mobile phase consists of an aqueous solution
      containing sodium sulfate, tetrahydrofuran, sodium 1-octanesulfonate and a
      phosphate buffer of pH 3.0. In contradistinction to methods previously published,
      this method not only allows a better separation of gentamicins C1, C1a, C2, C2a
      and C2b, but also the separation of several other, minor components, most of
      which were not identified. The effects of the different chromatographic
      parameters on the separation were also investigated. A number of commercial
      samples was analysed using this method, allowing sensitive detection of
      gentamicin without derivatization, and the results were compared with the results
      obtained with the European Pharmacopoeia method, prescribing pre-column
      derivatization.

PMID- 9919971
TI  - Analytical methods for the quality control of Prozac capsules.
AB  - Some analytical methods (two spectrophotometric and two chromatographic
      procedures) for the determination of fluoxetine in Prozac capsules are described.
      All of them are applied to the samples after extracting the drug with a methanol
      water mixture. The direct and derivative spectrophotometric methods are simple
      and reliable; the derivative method gives better recovery and lessens
      interference. Both methods show linearity in the 5-30 microg ml(-1) range of the
      fluoxetine concentration range. Both HPLC methods (spectrophotometric and
      spectrofluorimetric detection) use a tetramethylammonium perchlorate buffer
      acetonitrile mixture as the mobile phase and a C8 reversed phase column. The UV
      detection is performed at 226 nm, while the fluorimetric detection is performed
      by exciting at 230 nm and revealing the emission at 290 nm. The HPLC method with
      UV detection is more precise, but the procedure with fluorimetric detection is
      more sensitive.

PMID- 9919972
TI  - The use of hyphenated LC-MS technique for characterisation of impurity profiles
      during drug development.
AB  - As part of an integrated quality concept for impurities during drug development,
      the multidimensional evaluation of impurity profiles by LC MS coupling is
      presented using peptide drugs as an example. This quality concept can be regarded
      as an adaptation of the ICH-requirements to the special situation during the drug
      development process. The primary goal is to obtain qualitative molecular weight
      information for impurity peaks detected at the same UV wavelength as for the
      impurity test procedure. The approach is focused on the investigation, if the
      impurities in a clinical batch were also present in the toxicologically qualified
      batch(es). Depending on the relevance of individual impurities in further batches
      or as degradation products, the molecular weight can be used as a starting point
      for further characterization and identification. Often, eluents with volatile
      buffers required for MS result in different selectivities and/or inferior
      chromatographic separation and sensitivity compared with nonvolatile buffers
      (e.g. phosphates). In these cases, peak 'tracking' especially for small peaks can
      become critical. A procedure is presented for on-line coupling of LC methods with
      non-volatile eluents to mass spectrometry.

PMID- 9919973
TI  - Quantitative determination of polysorbate 20 in nasal pharmaceutical preparations
      by high-performance liquid chromatography.
AB  - A specific reverse-phase HPLC method has been developed for the quantitative
      determination of polysorbate 20 in various compositions of nasal solutions. This
      method is based on the acidic hydrolysis of the sorbitan laurate ester followed
      by the HPLC determination of the free lauric acid. Using this method, polysorbate
      20 can effectively be separated and quantitatively determined in matrices
      containing a wide variety of preservatives, surfactants, and viscosity agents.
      Sample preparation involves a one-step hydrolysis with sulfuric acid and then a
      dilution with acetonitrile, prior to injection. The sample is analyzed on a 5
      microm octadecylsilane reverse-phase column with a mobile phase of acetonitrile:
      0.025 M aqueous di-Sodium hydrogen phosphate, pH = 2.8 (75:25). The column
      effluent is monitored by UV detection at 210 nm. The validity of the method has
      been verified with specificity, linearity, recovery, method- and system
      precisions data. The method is linear for polysorbate 20 from 2.5 to 125 mg ml(
      1) range. The limit of detection and limit of quantitation are 0.41 and 0.61 mg
      ml(-1), respectively.

PMID- 9919974
TI  - Mechanism of separation on cholesterol-silica stationary phase for high
      performance liquid chromatography as revealed by analysis of quantitative
      structure-retention relationships.
AB  - The retention characteristics of a newly synthesized stationary phase were
      determined for reversed-phase high-performance liquid chromatography obtained by
      chemical immobilization of cholesterol on spherical silica gel. For a designed
      series of analytes the retention factors, log k, were determined at several
      compositions of the methanol-water mobile phase. Logarithms of retention factor
      corresponding to a hypothetical pure water eluent, log k(w), were calculated by
      extrapolation of the linear relationships of individual log k data versus volume
      percent of methanol. The series of 24 test analytes were characterized
      structurally by means of the logarithms of n-octanol-water partition
      coefficients, log P, by a set of the linear solvation energy relationship (LSER)
      based descriptors of the polarity and bulkiness of the analytes and by structural
      descriptors of analyte size and polarity acquired by molecular modelling.
      Quantitative structure retention relationships (QSRR) were derived by multiple
      regression analysis using the three groups of structural descriptors of analytes
      and the log k(w) data determined on the new stationary phase. For the sake of
      comparison the corresponding QSRR equations were also derived for retention
      parameters determined on a standard octadecylsilica and on the so-called
      immobilized artificial membrane (IAM) stationary phase. The QSRR analysis clearly
      proved distinctive retention properties of the new cholesterol-silica stationary
      phase. It has been concluded that the new phase may possess valuable analytical
      specificity. Its application for modelling penetration of xenobiotics through
      biological membranes appears rather unlikely.

PMID- 9919975
TI  - Development and validation of liquid chromatography and capillary electrophoresis
      methods for acarbose determination in pharmaceutical tablets.
AB  - Liquid chromatography and capillary zone electrophoresis, respectively coupled to
      an evaporative light scattering detector and a UV detector have been developed
      for the analysis of acarbose without any derivatization procedure. The
      electrophoretic separation of acarbose anomers was achieved through the
      manipulation of the working temperature. Both methods were validated and showed
      good validation data in terms of precision, accuracy and linearity. The validated
      methods were successfully applied to the dosage of acarbose in commercially
      available Glucobay tablets.

PMID- 9919976
TI  - Separation of a triterpenoid saponin mixture from Maesa lanceolata:
      semipreparative reversed-phase wide pore high performance liquid chromatography
      with temperature control.
AB  - A mixture of triterpenoid saponins derived from the dried leaves of Maesa
      lanceolata was separated, without structure deterioration, in its components.
      Seven fractions (I-VII) of high molecular weight (1234-1358) saponins were
      obtained on a semipreparative scale using wide pore reversed-phase high
      performance liquid chromatography with an acetonitrile trifluoroacetic acid
      (500:0.3 w/w)-water-trifluoroacetic acid (391:0.3, w/w) gradient from 35 to 56%
      in 30 min. The mobile phase was cooled in an ice bath (0 degrees C) during
      chromatography in order to prevent bubble formation and to improve the quality of
      the separation. Freeze-dried fractions IV, V, VI and VII were further separated
      using solvent systems developed for each of the fractions. Fourteen pure
      triterpenoid saponins were isolated in this way and their molar weight
      determined.

PMID- 9919977
TI  - Optimization of mobile phase in the separation of beta-blockers by HPLC.
AB  - Beta-blockers are generally determined using high-performance liquid
      chromatography (HPLC). Previous HPLC separations of beta-blockers have often
      required a mobile phase containing three components; acetonitrile or methanol to
      control the retention; buffer to control the ionic strength and pH of the mobile
      phase; ion-pairing reagent to provide adequate retention of beta-blockers or
      organic amines as masking agent to reduce peak tailing. Due to the complexity of
      the mobile phases employed, development of these assays can be a laborious
      process. Additionally, alkyl sulphonates and organic amines dramatically reduces
      the life-time reduction of silica based C18 columns. The results of this study
      demonstrated that the addition of tested alkyl sulphonates and organic amines is
      not essential for an adequate separation of beta-blockers. In this study, we
      developed a simple HPLC method for the simultaneous separation of model beta
      blockers, atenolol, practolol, metoprolol, oxprenolol and propranolol. Atenolol,
      practolol, metoprolol, oxprenolol and propranolol adequately separated with high
      peak symmetries using a mobile phase consisted of methanol/acetonitrile/phosphate
      buffer (10 mM, pH 3.0) (15:15:70, v/v/v). By altering only the fraction of
      methanol with respect to acetonitrile, method development becomes a more
      efficient separation. Furthermore, atenolol, practolol, metoprolol, oxprenolol
      and propranolol can be detected up to 0.25, 5, 10, 50 and 10 ng ml(-1). In this
      publication, we present the simultaneous separation of beta-blockers having a
      wide range of polarity. It is proposed that this new mobile phase, consisting
      only acetonitrile, methanol and phosphate buffer can be used for the analysis of
      the several beta-blockers presently in doping control analysis as well as others.

PMID- 9919978
TI  - Monitoring of tricyclic antidepressants in human serum and plasma by HPLC:
      characterization of a simple, laboratory developed method via external quality
      assessment.
AB  - A reversed-phase high performance liquid chromatography (HPLC) method for the
      determination of plasma and serum levels of amitriptyline (AMI), nortriptyline
      (NORT), imipramine (IMI), desipramine (DESI), clomipramine (CLOMI), and
      norclomipramine (NCLOMI) is described. The assay is based upon single step
      liquid/liquid extraction of these compounds using hexane at pH 11 (recovery
      between 92 and 105%), a Nova-Pack C-18 HPLC cartridge column, a mobile phase
      composed of a phosphate buffer with 50% (v/v) acetonitrile and about 0.2% (v/v)
      diethylamine (final pH: 8) and solute detection at 242 nm. Using 1 ml of plasma
      or serum and econazole as internal standard, drug levels between 20 and 400 ng
      ml(-1) (about 60-1450 nM) were found to provide linear calibration graphs. For
      drug concentrations in the range of 70-120 ng ml(-1) (about 240-430 nM), intraday
      and interday imprecisions (n = 5) were determined to be < 6.0, and < 15%,
      respectively. Data reported include those gathered over a 3-year period during
      which this assay was employed for therapeutic drug monitoring and clinical
      toxicology. The performance of the laboratory developed assay was assessed via
      analysis of monthly samples provided by an external quality control scheme.

PMID- 9919979
TI  - Determination of 13-cis-3-hydroxyretinoic acid, all-trans-3-hydroxyretinoic acid
      and their 4-oxo metabolites in human and animal plasma by high-performance liquid
      chromatography with automated column switching and UV detection.
AB  - A high-performance liquid chromatographic method with automated column switching
      was developed for the simultaneous determination of 13-cis-3-hydroxyretinoic
      acid, all-trans-3-hydroxyretinoic acid and their metabolites 13-cis-3-hydroxy-4
      oxo-retinoic acid and all-trans-3-hydroxy-4-oxo-retinoic acid in plasma samples
      from man, rat, dog, rabbit and mouse. The method consists of deproteination of
      plasma (0.4 ml) with ethanol (1.5 ml), containing the internal standard Ro 12
      7310. After centrifugation, 1.4 ml of the supernatant was directly injected onto
      the precolumn (PC) (4 x 4 mm) packed with LiChrospher 100 RP-18 (5 microm).
      Ammonium acetate (0.02%)-acetic acid-ethanol (100:3:4, v/v/v) was used as mobile
      phase M1A during injection, as well as to decrease the elution strength of the
      injection solution by on-line addition using a T-piece (M1B). After valve
      switching, the retained components were transferred to the analytical column
      (AC), separated by gradient elution and detected at 360 nm. Two coupled Purospher
      100 RP-18 endcapped columns (both 250 x 4 mm) were used for the separation,
      together with a mobile phase consisting of acetonitrile-water-10% ammonium
      acetate-acetic acid, (A), 540:450:2:30 (v/v/v/v), (B), 600:350:2:30 (v/v/v/v),
      and (C), 950:40:2:30 (v/v/v/v). The method was linear in the range 1-500 ng ml(
      1), at least, with a quantification limit of 1 ng ml(-1). The mean recoveries
      from human plasma were 100-107% and the mean inter-assay precision was 2.0-4.7%
      (range 1-500 ng ml(-1)). Similar results were obtained for animal plasma. The
      analytes were stable in the plasma of all investigated species stored at -20
      degrees C for 3 months, at least. The method was successfully applied to clinical
      and toxicokinetic studies.

PMID- 9919980
TI  - Determination of tramadol in various dosage forms by capillary isotachophoresis.
AB  - Cationic capillary isotachophoresis (ITP) with conductometric detection has been
      used for separating and determining milligram amounts of tramadol [2
      dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride] (I) in seven
      commercial mass-produced pharmaceutical preparations. The optimised ITP
      electrolyte system consisted of 5 mM potassium picolinate + 5 mM picolinic acid
      (pH 5.25) as the leading electrolyte and 10 mM formic acid as the terminating
      electrolyte. The driving and detection currents were 50 microA (for 320 s) and 10
      microA, respectively (a single analysis took 12-15 min). Under such conditions
      the effective mobility of I was determined as 24.26 x 10(-9) m2 V(-1) s(-1) (with
      tetraethylammonium ion as standard); thermodynamic pKa value of I was 9.44 +/-
      0.03 (n = 8) as determined by UV spectrophotometry at 25 degrees C and I = 0.01
      (NaCl). The calibration graph relating the ITP zone length to the concentration
      of I was rectilinear (r = 0.99997) in the range 15-180 mg l(-1) of I. The
      relative standard deviation (RSD) was 0.21% (n = 6) when determining 60 mg l(-1)
      of I in pure test solution. Sample pre-treatment of the dosage forms involved
      dilution or extraction of I with water (for suppositories the extraction was
      carried out in an ultrasonic bath at 40 degrees C for 10 min). The method was
      suitable for determining 50 or 100 mg ml(-1) of I in injections and drops, 50 mg
      of I in capsules, and 100 mg of I in suppositories with RSD values 0.4 to 1% (n =
      6). According to the validation procedure based on the standard addition
      technique the recoveries were 97.2-100.1% of I.

PMID- 9919981
TI  - The use of microemulsion electrokinetic chromatography in pharmaceutical
      analysis.
AB  - The use of a single set of microemulsion electrokinetic chromatography (MEEKC)
      separation conditions has been assessed for its applicability in the analysis of
      a range of pharmaceutical compounds. Particular emphasis was placed on neutral or
      very hydrophobic compounds, which can be difficult to analyse by conventional
      capillary electrophoresis. The microemulsion employed for the majority of
      separations consisted of 0.81% w/w octane, 6.61% w/w 1-butanol, 3.31% w/w sodium
      dodecyl sulphate and 89.27% w/w 10 mM sodium tetraborate buffer. Good separations
      of methyl, ethyl, butyl and propyl hydroxybenzoates, and a range of ionic and
      neutral water soluble and insoluble compounds was achieved using a single set of
      separation conditions. A number of novel applications of MEEKC were developed
      included the simultaneous determination of the active components and
      preservatives in liquid formulation and determination of drug related impurities.
      Improved performance was obtained through use of internal standards and
      preparation of the samples dissolved in the microemulsion solution. Validation
      aspects such as linearity, repeatability, accuracy, injection precision and
      sensitivity were successfully assessed.

PMID- 9919982
TI  - Stereoselective determination of S-naproxen in tablets by capillary
      electrophoresis.
AB  - A capillary electrophoresis (CE) method was developed for the stereoselective
      determination of the non-steroidal anti-inflammatory drug (NSAID), S-naproxen, in
      tablets. Several beta-cyclodextrin derivatives (CDs) were tested as chiral
      selectors, including sulfobutyl-beta-CD (SBCD), carboxymethyl-beta-CD (CMCD),
      dimethyl-beta-CD (DMCD) and trimethyl-beta-CD (TMCD), in a phosphoric
      acid/triethanolamine pH 3 buffer. Under these conditions, the analyte was mainly
      present in an uncharged form and therefore, the use a neutral CD (DMCD or TMCD)
      alone could not lead to enantiomeric separation. On the contrary, by addition of
      a charged CD (SBCD or CMCD) to the running buffer, giving the analyte enantiomers
      an adequate mobility, chiral resolution could be achieved, although the
      resolution values obtained in this case were not quite satisfactory (Rs < 1.5).
      Dual systems, based on the use of mixtures of charged and neutral CDs, were then
      investigated. The SBCD/TMCD system was found to be particularly well suited to
      the enantioseparation of naproxen and after optimisation of the concentrations of
      both CDs, a resolution value of 5.4 could be obtained. The method was validated
      for the determination of R-naproxen (enantiomeric impurity) in the 0.1-2% range,
      using the racemic mixture of the analyte. A second validation was performed in
      the 50-150% range for the quantitation of S-naproxen. In both cases, good results
      with respect to linearity, precision and accuracy were obtained.

PMID- 9919983
TI  - Development and optimisation of a generic micellar electrokinetic capillary
      chromatography method to support analysis of a wide range of pharmaceuticals and
      excipients.
AB  - A micellar electrokinetic capillary chromatography (MECC) method has been
      developed and validated to allow the analysis of a wide range of water soluble
      and insoluble acidic, basic and neutral drugs and excipients. An electronic
      database has been established to demonstrate the wide applicability of the
      method. The method has been validated and is now in routine use. In particular,
      acceptable injection precision is obtained through use of internal standards.
      Optimal sensitivity was obtained by using low UV wavelength detection. The method
      allows a number of cost and time saving benefits.

PMID- 9919984
TI  - Capillary electrophoresis for the analysis of tropane alkaloids: pharmaceutical
      and phytochemical applications.
AB  - Three capillary electrophoresis methods, using UV detection, were developed for
      the simultaneous determination of several tropane alkaloids, including atropine,
      scopolamine and synthetic derivatives. After optimization, the validated
      capillary zone electrophoresis methods were applied to the determination of these
      compounds in various pharmaceutical forms, such as ophthalmic and injection
      solutions, tablets, suppositories and aerosols. Capillary electrophoresis in the
      micellar mode was found to be more appropriate for the analysis of hyoscyamine
      and scopolamine in plant material. These two compounds are generally found
      together with other tropane alkaloids which present similar structures and charge
      to mass ratio. Furthermore, the separation of positional isomers, such as
      hyoscyamine and littorine generally encountered in plant extracts, was also
      considered. The developed method was applied to the analysis of hairy root
      extracts of Datura candida x Datura aurea, Datura quercifolia and Hyoscyamus
      albus.

PMID- 9919985
TI  - Simultaneous determination of dextromethorphan and its metabolites in human
      plasma by capillary electrophoresis.
AB  - A sensitive capillary electrophoretic method was developed and validated for the
      simultaneous determination of dextromethorphan and its metabolites, dextrorphan,
      3-hydroxymorphinan, and 3-methoxymorphinan, in human plasma. After cleavage of
      conjugates by enzymatic hydrolysis with beta-glucuronidase, dextromethorphan and
      its metabolites were extracted from 1.5 ml of plasma by a liquid liquid
      extraction procedure using heptane-ethylacetate (50:50, v/v) and re-extracted to
      aqueous phase. The compounds were separated within 8 min on a fused silica
      capillary, 75 microm internal diameter using sodium borate (pH 9.4; 50 mM) as
      running buffer, and measured by UV-detection at 195 nm using a detection cell
      with a path length of 1.2 mm. The method was accurate and precise. Linear
      relationships were observed between the peak response and the concentration in
      the range of 1-400 ng ml(-1) plasma with correlation coefficients above 0.998.
      The limit of detection was 0.5-1 ng ml(-1) plasma for all compounds. The method
      was used for determination of plasma levels of dextromethorphan and its
      metabolites after transdermal and oral administration of dextromethorphan.

PMID- 9919986
TI  - Determination of tetracycline and its major degradation products by liquid
      chromatography with fluorescence detection.
AB  - A liquid chromatographic method of tetracycline and its major degradation
      products on a C8-reversed phase column with acidic mobile phase and fluorescence
      detection is described. The quantification limit, measured as the amount of
      sample that gave a signal ten times the peak-to-peak noise of the baseline, was:
      0.25 ng for tetracycline (TC) and epitetracycline (ETC), 25 ng for and 4
      epianhydrotetracycline (EATC) and 50 ng for anhydrotetracycline (ATC) of injected
      standard. By means of this liquid chromatography (LC) assay TC, ETC, EATC and ATC
      as main degradation products of tetracycline, can be separated and determined
      with good sensitivity and specificity within 15 min.

PMID- 9919987
TI  - Determination of protein binding of gyrase inhibitors by means of continuous
      ultrafiltration.
AB  - In order to characterize the protein binding of a drug, it is necessary to have a
      method which is close to in vivo conditions and fast in the course of
      measurement. The continuous ultrafiltration fulfils both requirements for
      substances with a high extent of protein binding. In this study, 18 gyrase
      inhibitors in clinical practice, characterized by a lower extent of protein
      binding, were subjected to the titration procedure of the continuous
      ultrafiltration using bovine and human serum albumin (BSA, HSA), and human
      plasma. The results of the continuous ultrafiltration were found to be similar to
      those obtained by means of the 'classical' discontinuous ultrafiltration using
      plasma (correlation between continuous and discontinuous ultrafiltration r2 =
      0.87). In the cases of pipemidic acid, enoxacin and rufloxacin, the continuous
      method gave approximately 20% lower degrees of protein binding than the
      discontinuous procedure, which utilizes plasma having the full range of proteins.
      It is likely that these drugs bind mainly to other proteins in plasma than HSA.
      This finding proves that this fast method is worthwhile in the whole range of
      protein binding.

PMID- 9919988
TI  - Study of acid-base equilibria of fleroxacin.
AB  - The acid-base equilibria of fleroxacin were studied by means of potentiometry and
      spectrophotometry. It was established that fleroxacin undergoes a complex acid
      base equilibrium due to its zwitterionic nature and two proton-binding sites of
      similar acidity. The stoichiometric equilibrium constants were determined at 25
      degrees C and constant ionic strength 0.1 M (NaCl). The acidity constants pK1 =
      5.59 +/- 0.01 and pK2 = 8.08 +/- 0.04 were found by potentiometry, and pK1 = 5.61
      +/- 0.03 and pK2 = 8.11 +/- 0.06 by spectrophotometry. The distribution diagram
      of the corresponding ionic species is given.

PMID- 9919989
TI  - The effect of photodegradation on the fluorescent properties of norfloxacin:
      (photodegradation and fluorescence of norfloxacin).
AB  - Norfloxacin (NFLX), a broad spectrum antibacterial quinolone, is a very
      thermostable but photosensitive drug, especially in solution leading to the
      formation of an ethylenediamine degradate. The modification of the fluorescent
      properties of NFLX in acid solution after exposure to fluorescent light and the
      degradation mechanisms were studied. Two analytical methods were previously
      developed and validated for NFLX, ultraviolet spectrophotometry (UV) and
      spectrofluorimetry (FL). Data obtained using both methods in the analysis of
      remaining NFLX in terms of percent recoveries revealed that there was no
      statistically significant modifications of the UV signal and of the recoveries
      obtained by the method. However, an important increase of the fluorescent signal
      after light exposure of NFLX solutions appeared, which led to an increase of the
      average recovery up to 270% over 15 months. Using a previously validated HPLC
      method for the photostability studies of NFLX, a loss of 5% with respect to the
      initial drug amount was observed. The study of UV and fluorescence spectra
      evidenced the formation of the degradation product, which induced significant
      modification of the fluorescent properties of NFLX samples. These results clearly
      indicated that FL analysis definitively is the method of choice and can be used
      to study the photodegradation of NFLX.

PMID- 9919990
TI  - Simultaneous determination of salicylic acid and acetylsalicylic acid in aspirin
      delayed-release tablet formulations by second-derivative UV spectrophotometry.
AB  - A rapid, simple assay procedure was developed for simultaneous analysis of
      aspirin (ASA) and salicylic acid (SA) in aspirin delayed-release tablet
      formulation by 'zero crossing' second-derivative UV spectrophotometry. The zero
      order absorption spectra and second derivative spectra of ASA and SA were
      recorded in diluting solution acetonitrile-formic acid (99:1). The accuracy of
      the method was demonstrated by the determination of ASA and SA in five tablets
      formulations (each 20 tablets of the same batch) by the described method and by
      high performance liquid chromatographic method, and the results were in good
      agreement.

PMID- 9919991
TI  - Spectrophotometric determination of some catecholamine drugs using sodium
      bismuthate.
AB  - A novel spectrophotometric method is described for the determination of
      epinephrine (EP) and norepinephrine (NE). The method is based on the development
      of a red colour with sodium bismuthate, as a sensitive chromogenic reagent, in
      aqueous medium at pH 3. Oxidation of these catecholamines produces aminochrome
      derivatives which can be measured spectrophotometrically at 486.0 nm. Calibration
      graphs are linear in the range 4.8-800 (micromol l(-1)) for epinephrine
      bitartarate and 4.8-600 (micromol l(-1)) for norepinephrine bitartarate with
      detection limits of 0.26 (micromol l(-1)) and 2.46 (micromol l(-1)) for
      epinephrine and norepinephrine bitartarate salts, respectively. The method has
      successfully been applied to determination of these catecholamines in
      pharmaceutical preparations.

PMID- 9919992
TI  - Spectrophotometric determination of some vic-diol containing drugs using ion
      exchange resins.
AB  - Periodic acid and its salts have been widely used for the quantitative oxidation
      of vic-diol containing compounds including carbohydrates and catecholamine drugs.
      The advantage of using a polymeric resin (periodate form) over free periodate
      ions is that the resin quantitatively retains both unconsumed periodate ions and
      the iodate ions produced in the oxidation and, hence, enables one to undertake
      further studies on the structural, synthetic or preparative work. The resin
      (periodate form) was found to be a clean and sensitive chromogenic reagent for
      the spectrophotometric determination of some catecholamine drugs. The calibration
      graphs of absorption versus concentration in the range studied (5-50 ppm) were
      linear.

PMID- 9919993
TI  - Enzymatic analysis of acetylpolyamine.
AB  - An enzymatic method was proposed for measuring acetylpolyamine (AcPA) alone, even
      when non-acetylated polyamine co-exists. The method consisted of four enzymatic
      reactions. First, AcPA was hydrolysed by acylpolyamine amidohydrolase to yield
      acetate; followed by the other three reactions coupled with three enzymes,
      respectively, acetate kinase, pyruvate kinase, and lactate dehydrogenase; the
      acetate formation caused a decrease in NADH. The quantity of AcPA was then
      evaluated as the change in absorbance at 340 nm. The reagent composition of the
      reaction mixture was determined, and characteristics of the method were
      investigated. The validation tests produced satisfactory results. The co
      existence of non-acetylated polyamine gave no effect on the measurement. The
      present method was found to be used easily, rapidly and reliably for the
      selective determination of AcPA itself.

PMID- 9919994
TI  - HPTLC determination of ceftriaxone, cefixime and cefotaxime in dosage forms.
AB  - The objective of this investigation was to develop a HPTLC method for the
      determination of ceftriaxone, cefixime and cefotaxime, cephalosporins widely used
      in clinical practice. High performance TLC of cephalosporins was performed on pre
      coated silica gel HPTLC plates with concentrating zone (2.5 x 10 cm) by
      development in mobile phase ethyl acetate-acetone-methanol-water (5:2.5:2.5:1.5
      v/v/v/v). A TLC scanner set at 270 nm was used for direct evaluation of the
      chromatograms in reflectance/absorbance mode. The calibration curves were
      established as dependence of peak height (linear and polynomial regression) and
      peak area (polynomial regression) versus ng level (125-500 ng for all
      cephalosporins investigated). Relative standard deviations obtained from
      calibration curves was compared. Precision (RSD: 1.12-2.91% (peak height versus
      ng) and RSD: 1.05-2.75% (peak area versus ng)), and detection limits (ng level)
      was validated and found to be satisfactory. The method was found to be
      reproducible and convenient for quantitative analysis of ceftriaxone, cefixime
      and cefotaxime in their raw materials and their dosage forms.

PMID- 9919995
TI  - An improved HPLC method overcoming Beer's law deviations arising from
      supramolecular interactions in tolfenamic acid and cyclodextrins complexes.
AB  - Inclusion complexes of tolfenamic acid (TA), a non-steroidal anti-inflammatory
      drug, with methyl-beta cyclodextrin and hydroxypropyl-beta cyclodextrin were
      prepared and characterised. Spectrophotometric, chromatographic (RP-HPLC) and 1H
      NMR studies of the complexes were conducted. It was observed that cyclodextrins
      influence TA's molar absorptivity leading to Beer's law deviation. Consequently,
      the accuracy problem arose, urged for the application of specific chromatographic
      conditions for the determination of TA in the presence of CDs. A new HPLC method
      was developed and validated. TA was analysed on a C18 column 5 microm (150 x 4.6
      mm), using a column thermostat regulated at 30 degrees C. The mobile phase
      consisted of methanol-phosphate buffer solution (pH 3.2; 0.07 M) (90:10 v/v) and
      the flow rate was set at 2.0 ml min(-1). The detector was operated at 286 nm. TA
      was successfully determined, overcoming the problems arising from the presence of
      cyclodextrins.

PMID- 9919996
TI  - Determination of protamine sulphate in drug formulations using high performance
      liquid chromatography.
AB  - Protamine sulphate, which has the property of neutralising heparin, is determined
      in pharmaceutical formulations using spectrophotometric (BP 1995) or biochemical
      methods (USP XXIII 1995). Accuracy of these methods is not very high. We applied
      the HPLC technique for the assay of protamine sulphate in a gel formulation. The
      assay was carried out on a diol-type column with a mobile phase containing 8%
      acetonitrile in 0.15% trifluoroacetic acid at pH 2.5. The flow rate was 1.0 ml
      min(-1). The results obtained show that HPLC can be used for the determination of
      protamine sulphate in pharmaceutical preparations. The method is rapid and more
      accurate than those described until now.

PMID- 9919997
TI  - Evaluation and optimisation of separation buffers for the determination of
      corticosteroids with micellar electrokinetic capillary chromatography (MECC).
AB  - Separation buffers for the determination of the corticosteroids cortisone,
      hydrocortisone, prednisone and prednisolone with micellar electrokinetic
      chromatography were developed with respect to separation efficacy and the
      migration times, depending on the type and the concentration of the organic
      modifier acetonitrile as well as on the addition of gamma-cyclodextrin. The
      buffer containing 50 mM SDS and 16% (v/v) acetonitrile enables the rapid
      profiling of prednisolone together with cortisone and prednisone. Addition of
      gamma-cyclodextrin alters the elution sequence, but does not further enhance
      resolution of the corticosteroids. Baseline separation at long migration times
      for cortisone, hydrocortisone, prednisone and prednisolone is achieved with a
      buffer containing 50 mM each of SDS, dehydrocholic acid sodium salt and
      glycodeoxycholic acid sodium salt.

PMID- 9919998
TI  - The frequency of a common mutation of the methionine synthase gene in the
      Australian population and its relation to smoking and coronary artery disease.
AB  - BACKGROUND: Modest elevations in levels of circulating homocysteine are common in
      patients with vascular disease. Methionine synthase is a vitamin B12-dependent
      enzyme catalysing the re-methylation of homocysteine to methionine; reduced
      methionine synthase activity results in elevated level of homocysteine. DESIGN: A
      case-control study. METHODS: We explored the frequency and distribution of a
      2756A-->G (D919G) mutation of the methionine synthase gene, detected by
      polymerase chain reaction genotyping, in 745 Australian Caucasian patients aged <
      or = 65 years (550 men and 195 women) with and without angiographically
      documented coronary artery disease (CAD). RESULTS: The frequency distributions of
      AA, AG and GG genotypes were 61.9%, 33.8% and 4.3%, respectively, and were in
      Hardy-Weinberg equilibrium. There was no correlation between the methionine
      synthase mutation and CAD from simple chi2 comparison. However, the interactive
      term of life-time smoking dose with methionine synthase genotypes was predictive
      of both the number of significantly diseased vessels (> or =50% luminal
      obstruction; chi2 = 12.518, P=0.0019), and the presence or absence of significant
      CAD (chi2=7.045, P=0.027). A stepwise logistic regression analysis showed that
      smokers who were also GG homozygotes had more severe CAD compared with smokers of
      other genotypes. The methionine synthase genotypes were not associated with any
      of the other established CAD risk factors assessed in our study. CONCLUSIONS: We
      conclude that the methionine synthase 2756A-->G mutation is common, with
      homozygosity occurring in approximately 4% of white Australians, and that it has
      an interactive effect with life-time smoking dose to increase the severity of
      CAD. Smokers who are also GG homozygotes have additionally elevated CAD risk.

PMID- 9919999
TI  - Acute complications and restenosis in women undergoing percutaneous transluminal
      coronary angioplasty. Is it possible to define sex differences and to determine
      risk factors?
AB  - BACKGROUND: Several investigators report a sex bias in the treatment of coronary
      artery disease. This study attempts to define sex differences in the outcome of
      percutaneous transluminal coronary angioplasty (PTCA) and to determine risk
      factors contributing to these results. RESULTS: Data were collected from 1082
      patients (887 men and 195 women). In women, the risk of abrupt vessel closure
      (8.1% versus 2.5%, odds ratio 3.46) and of myocardial infarction (6.2% versus
      1.2%, odds ratio 5.58) following PTCA for stable angina pectoris was
      significantly increased. History of myocardial infarction and PTCA of a vessel of
      less than 3.0 mm diameter predicted abrupt vessel closure in women. Age and
      cardiovascular risk factors were not predictors. The incidence of restenosis did
      not differ significantly (angiographic restenosis in women 36.1% versus 40.8% in
      men, P=0.34). CONCLUSIONS: A significantly increased risk of acute complications
      could only be documented in women undergoing PTCA for stable angina pectoris and
      not in acute coronary syndrome. Long-term outcome was similar between the two
      sexes.

PMID- 9920000
TI  - Interethnic differences in coronary heart disease mortality in 25 populations:
      association with the angiotensin-converting enzyme DD genotype frequency.
AB  - BACKGROUND: Despite changes in dietary habits and steadily increasing serum
      cholesterol concentrations, coronary heart disease (CHD) mortality rates in
      developed South-East Asian populations are still one quarter those in many
      Western populations. We propose that genetic factors may, in part, contribute to
      these differences in CHD mortality. DESIGN: Using an ecological study design, we
      have investigated the comparative roles of serum cholesterol concentration and
      the angiotensin-converting enzyme (ACE) homozygote deletion (DD) genotype
      frequency, which has recently been implicated in CHD mortality. METHODS: Using
      our genotyping data from local Chinese populations, together with previously
      published data on ACE gene frequency and cholesterol concentrations, we
      correlated ACE DD genotype frequencies and mean serum cholesterol concentrations
      with World Health Organization age-adjusted CHD mortality rates in 25 ethnically
      diverse populations. RESULTS: Although mean serum cholesterol accounted for 67%
      of the variance in CHD mortality rates for all populations (r=0.82, 95% Cl 0.63
      0.92, n=25, P<0.001), the ACE DD frequency accounted for 61% of the variance in
      'low' cholesterol populations (r=0.78, 95% Cl 0.43-0.91, n= 14, P<0.001) with no
      additional contribution from serum cholesterol concentration. Moreover, in the
      'low' cholesterol population, mean serum cholesterol accounted for only 37% of
      the variance. CONCLUSION: We hypothesize that differences in the frequency of the
      ACE DD genotype in populations with low mean serum cholesterol concentrations may
      play some part in determining interethnic differences in CHD mortality rates.

PMID- 9920001
TI  - Blood lipid and lipoprotein concentrations in active, sedentary, healthy and
      diseased men.
AB  - AIM: To examine differences in resting blood lipid and lipoprotein concentrations
      in male subjects of varying degrees of cardiovascular fitness ranging from the
      healthy elite athlete to the sedentary subject either with or without
      angiographically confirmed evidence of coronary artery disease (CAD). METHODS:
      Two-hundred-and-eighty-four clinically asymptomatic male subjects were selected
      from a group of Olympic distance runners (n = 1 7), physical education athletes
      (n = 44), and industrial executives (n = 223). Each subject received a detailed
      physical examination and provided a venous blood sample after fasting, which was
      analysed for lipid and lipoprotein concentrations. Maximum oxygen uptake was
      determined using on-line computerised respiratory analysis during a functional
      diagnostic test. The industrial executive group was further divided according to
      their electrocardiographic (ECG) response to exercise; negative ECG (n = 138),
      positive (abnormal) ECG but no angiographic evidence of CAD (n = 18) and positive
      ECG with angiographic evidence of significant CAD (n=67). RESULTS: Lipid
      lipoprotein profiles were consistently abnormal in subjects with a positive ECG
      and documented evidence of CAD, whereas those subjects who tested negative or
      false-positive were less affected. The lipid-lipoprotein profiles observed
      between Olympic distance runners and an age-matched group of physically active
      students were not significantly different despite clear differences in physical
      activity patterns. CONCLUSIONS: In addition to the abnormal lipid-lipoprotein
      profile in subjects with CAD, the present data also suggest that while physical
      activity confers metabolic cardioprotection, a threshold stimulus exists beyond
      which no further benefits can be gained.

PMID- 9920002
TI  - Ambulatory blood pressure and risk factors for coronary heart disease in black
      and Indian medical students.
AB  - BACKGROUND: Coronary heart disease (CHD) has reached 'epidemic' proportions in
      South Africa. CHD is uncommon in the black population of South Africa, yet the
      prevalence of hypertension in the adult black population is high. DESIGN: This
      study compared the blood pressure profile in 154 medical students of which 83
      were Indians (1), 71 were black (B), 87 were male (50 I, 37 B), and 67 were
      female (33 I, 34 B) age 21 (SD+/-1.6), using the cuff method and 24 h ambulatory
      blood pressure monitoring (ABPM). METHODS: All students underwent ABPM.
      Biochemical studies for CHD risk factors were done. Electrocardiography (ECG) was
      performed in all participants and echocardiography in 90. RESULTS: ABPM showed
      that black students had higher systolic and diastolic blood pressure throughout
      the day, night and critical time periods compared with the Indian students. Blood
      pressure load was higher in black (40.8%) than in Indian participants (29.6%;
      P<0.05) and there was less dipping at night Left ventricular mass was
      significantly higher in black than in Indian participants (29.6%; P<0.05) and
      there was less dipping at night. Left ventricular mass was significantly higher
      in black than in Indian participants. Risk factors leading to CHD were more
      common in Indian than in black participants. Those with borderline hypertension
      (blood pressure > or = 130/85 and < or = 140/90 mmHg) had statistically higher
      serum triglyceride and left ventricular mass than normotensives. CONCLUSIONS:
      Young black people had higher blood pressure readings than young Indian
      participants in the absence of metabolic abnormalities and had greater cardiac
      involvement Borderline hypertension is not innocuous. Metabolic risk factors for
      CHD in Indian people are apparent at an early age. This study emphasizes the need
      for prevention of risk factors leading to CHD at an early age.

PMID- 9920003
TI  - Effect of smoking on the prevalence of insulin resistance-associated
      cardiovascular risk factors among Finnish men in military service.
AB  - BACKGROUND: Obesity, central obesity, hypertension, dyslipidemia and
      hyperinsulinemia tend to cluster in the same individuals as a metabolic syndrome;
      smoking has an adverse effect on insulin resistance. The aim of our study was to
      examine the occurrence of clusters of insulin-resistance-associated abnormalities
      and the effect of smoking on this clustering in young men. METHODS: In 1995 we
      invited all the 1268 servicemen attending military service in the Ostrobothnian
      Brigade, Finland, for screening of the metabolic syndrome. The first phase
      consisted of an interview concerning smoking and measurements of blood pressure,
      weight, height, waist and hip circumferences. If diastolic pressure was > 85
      mmHg, body mass index > 27 or waist-to-hip ratio > 0.98, these participants were
      invited to blood samples for the measurements of fasting serum lipids, plasma
      glucose and insulin. These results were obtained from 144 screening-positive men
      (120%) and from their 79(7%) randomly selected controls. RESULTS: The metabolic
      syndrome, defined as plasma insulin > or = 13.0 mU/l and serum triglycerides > or
      = 1.70 mmol/l and/or total cholesterol/high-density lipoprotein cholesterol >
      5.0, was present in 10% (n = 1 4) of the screening-positive participants. None of
      the randomly selected controls had the metabolic syndrome. The metabolic syndrome
      was present in 12% (n = 11) of 93 smokers and in 2% (n = 3) of 1 28 non-smokers
      (P= 0.004). CONCLUSIONS: We conclude that clusters of metabolic abnormalities
      associated with insulin resistance are already present in young men, and that the
      prevalence of these clusters in smokers is sixfold compared with non-smokers.

PMID- 9920004
TI  - Coronary heart disease risk factors in subjects whose brothers, sisters or
      husbands developed premature myocardial infarction during 12 years of follow-up.
      The Finnmark Study (1977-1989).
AB  - BACKGROUND: In individuals whose relatives have experienced heart disease, levels
      of classic risk factors may have been underestimated because of life style
      changes after serious family disease or inaccurate disease reports. METHODS: To
      overcome pitfalls noted in previous research, risk factors were measured at a
      screening of the general population aged 20-52 years in four Norwegian
      municipalities. After 12 years of follow-up, a first myocardial infarction was
      evident in 51 of 753 sibships and in 68 of 1518 spouse pairs. RESULTS: Multiple
      adjusted means were higher in men with than in men without a brother or sister
      who became affected: 7.17 versus 6.84 mmol/l (P=0.07) for serum total
      cholesterol, 140.8 versus 135.6 mmHg (P=0.02) and 85.7 versus 82.5 mmHg (P=0.04)
      for systolic and diastolic blood pressure. Total cholesterol readings were higher
      the younger (P < 0.01 ) the sibling who experienced heart disease. Elevations
      were less pronounced in women, but smoking was more frequent among wives of
      affected than wives of unaffected husbands (58.3% versus 41.2%, P<0.01).
      CONCLUSIONS: The markedly adverse levels of modifiable risk factors found in
      individuals whose brothers or sisters developed heart disease offer a potential
      for prevention in families with heart disease.

PMID- 9920005
TI  - Restenosis after percutaneous transluminal coronary angioplasty in patients with
      non-insulin-dependent diabetes mellitus (NIDDM).
AB  - BACKGROUND: The effect of glycemic control on the incidence of restenosis after
      percutaneous transluminal coronary angioplasty (PTCA) in non-insulin-dependent
      diabetes mellitus (NIDDM) has not been well analysed. METHODS: Out of 1282
      consecutive patients who had undergone elective and successful PTCA over 8 years,
      86 known to have NIDDM and 117 non-diabetic cases were analysed for restenosis
      following PTCA. Definition of restenosis is an increase from 50% to 75% diameter
      stenosis at the same lesion within 1 year after angioplasty. Those with familial
      hypercholesterolemia, renal failure, unstable angina pectoris, bypass graft
      surgery within 1 month were excluded. Blood pressure, body mass index, history of
      smoking, fasting blood glucose, post-prandial glucose, HbA1c, cholesterol,
      triglycerides, number of stenotic vessels, restenosis rate were studied - 6
      months before PTCA and 1, 3, 6 and 12 months after PTCA. RESULTS: The frequency
      of restenosis within 1 year of PTCA was significantly greater in poorly
      controlled NIDDM (75%) than in well or moderately controlled NIDDM (30-40%) or
      non-diabetic subjects (33%). Multivariate analysis showed that the degree of
      control of diabetes was significantly correlated with restenosis. CONCLUSION:
      Restenosis following elective and successive PTCA was significantly more frequent
      in poorly controlled NIDDM compared with moderately or well-controlled NIDDM or
      non-diabetic subjects. Multivariate analysis also showed the significant
      correlation between restenosis and glycemic control. These findings indicate that
      control of diabetes plays an important role in reducing restenosis after PTCA.

PMID- 9920006
TI  - A novel serum protein of molecular weight 182 kDa: a molecular marker for an
      early detection of increased left ventricular mass in patients with cardiac
      hypertrophy.
AB  - BACKGROUND: Earlier studies in our laboratory have shown the presence of a
      cardiac-hypertrophy-specific high-molecular-weight protein of 182 kDa in the sera
      of laboratory rats which were subjected to aortic stenosis. On the basis of a
      number of criteria, these studies have pointed out that this protein may be a
      molecular signal of hypertrophic growth in the aorta-constricted animals.
      Further, a similar high-molecular-weight protein has been observed in the sera of
      normal humans and patients with cardiac anomalies. We have tried to correlate the
      levels of 182 kDa serum protein with various parameters such as age, severity of
      hypertrophy and left ventricular muscle (LVM) mass in patients with cardiac
      hypertrophy. METHODS: Two hundred and ten patients with left and right
      ventricular hypertrophy evidenced by clinical history, physical examination,
      electrocardiogram and echocardiogram were selected for the study. Sandwich enzyme
      linked immunosorbent assay (ELISA) technique was used to quantify the 182 kDa
      serum protein in the sera of patients by using anti-rat 182 kDa protein
      antibodies. RESULTS: The 182 kDa protein levels in the serum correlated with the
      age and stage of the LVM mass of hypertrophied heart in patients. It was noted
      that this protein was significantly elevated in early and moderate stages of
      cardiac hypertrophy and decreased when the hypertrophy became severe in patients
      only up to 40 years of age, whereas no significant difference exists in 182 kDa
      protein levels between normal individuals and patients with cardiac hypertrophy
      aged over 40 years. CONCLUSION: The level of this protein could be an early
      molecular marker identifying the stages of increase in LVM mass in patients with
      cardiac hypertrophy, below 40 years of age. The induction of 182 kDa protein
      levels in human serum may be an age-dependent phenomenon.

PMID- 9920007
TI  - Alpha-tocopherol but not beta-tocopherol inhibits thrombin-induced PKC activation
      and endothelin secretion in endothelial cells.
AB  - INTRODUCTION: Production of endothelin by endothelial cells depends on protein
      kinase C (PKC) stimulation which has been reported to be inhibited by alpha
      tocopherol (alpha-Toch) but not by beta-tocopherol (beta-Toch). The goal of this
      study was to determine whether alpha-Toch and beta-Toch inhibit endothelin
      secretion by endothelial cells. METHODS: and results In a first set of
      experiments, cultured bovine aortic endothelial cells (BAEC) were incubated for
      48h with 100 micromol/l alpha-Toch or vehicle (0.1% ethanol), then cells were
      stimulated for 4 h or 20 h with thrombin. After stimulating bovine aortic
      endothelial cells with thrombin for 4 h, alpha-Toch inhibited PKC activity by 63%
      and endothelin secretion by 44%, whereas after 20 h of incubation with thrombin,
      alpha-Toch decreased the peptide secretion by 51%. In a second set of
      experiments, BAEC were incubated with increased concentrations (from 0 to 100
      micromol/l) of alpha-Toch or beta-Toch, PKC activity and endothelin secretion
      were measured after thrombin stimulation as previously reported. In these
      experiments, alpha-Toch strongly inhibited thrombin-induced PKC activity and
      endothelin secretion in a dose-dependent manner, whereas beta-Toch was more than
      10-fold less active than alpha-Toch in inhibiting these stimulations. Tocopherols
      (alpha-Toch + beta-Toch) produced a proportional correlation on both PKC
      stimulation and endothelin secretion by inhibiting the effect of thrombin.
      CONCLUSION: These data suggest that alpha-Toch strongly inhibits thrombin-induced
      endothelin secretion in vitro at least partly through PKC inhibition.

PMID- 9920008
TI  - Gene therapy for rheumatic diseases.

PMID- 9920009
TI  - Incidence and risk factors for radiographic knee osteoarthritis in middle-aged
      women: the Chingford Study.
AB  - OBJECTIVE: To examine the natural history, role of risk factors, and incidence of
      knee osteoarthritis (OA) in a prospective study of women from a population
      cohort. METHODS: Women from the Chingford Study who had been recruited in 1989
      were followed up with knee radiographs 4 years later. A total of 715 paired
      radiographs (71% of the original sample) were graded for osteophytes and 644 for
      joint space narrowing (JSN). Women whose radiographs had been graded as 0 in 1989
      and as > or =14 years later were classified as having incident disease. Incident
      cases were compared with controls for associations with a number of risk factors.
      RESULTS: Eighty-one women (12.6%) developed JSN of the knee, equating to an
      incidence of 3.1% per year. No clear risk factors for JSN were identified.
      Reproducibility of measures of joint space is poor, however, leading to
      inaccuracy of definition. Incident knee osteophytes developed in 95 women (133%),
      equating to an incidence of 3.3% per year. Compared with controls, women with
      incident knee osteophytes were older, heavier, and had more hand OA and knee
      symptoms. Women in the top tertile of obesity (body mass index >26.4) had a
      significantly increased risk of incident knee osteophytes (odds ratio [OR] 2.38,
      95% confidence interval [95% CI] 1.29-4.39). Incident knee osteophytes increased
      by 20% per 5-year age increase. A nonsignificant protective effect for incident
      knee osteophytes was seen with current estrogen replacement therapy (ERT) (OR
      0.41, 95% CI 0.12-1.42). No effect was associated with smoking, physical
      activity, hysterectomy, or previous knee injury. CONCLUSION: Obesity and aging
      are associated with a high risk of new knee OA developing in women. Evidence of a
      protective effect of ERT was seen. No clear association was found for incident
      JSN, suggesting that different etiologic mechanisms are operating or that
      standard radiographs are an inaccurate measure of incident narrowing.

PMID- 9920010
TI  - Does laxity alter the relationship between strength and physical function in knee
      osteoarthritis?
AB  - OBJECTIVE: Since strengthening interventions have had a lower-than-expected
      impact on patient function in studies of knee osteoarthritis (OA) and it is known
      that laxity influences muscle activity, this study examined whether the
      relationship between strength and function is weaker in the presence of laxity.
      METHODS: One hundred sixty-four patients with knee OA were studied. Knee OA was
      defined by the presence of definite osteophytes, and patients had to have at
      least a little difficulty with knee-requiring activities. Tests were performed to
      determine quadriceps and hamstring strength, varus-valgus laxity, functional
      status (Western Ontario and McMaster Universities Osteoarthritis Index Physical
      Functioning subscale [WOMAC-PF] and chair-stand performance), body mass index,
      and pain. High and low laxity groups were defined as above and below the sample
      median, respectively. RESULTS: Strength and chair-stand rates correlated (r =
      0.44 to 0.52), as did strength and the WOMAC-PF score (r = -0.21 to -0.36). In
      multivariate analyses, greater laxity was consistently associated with a weaker
      relationship between strength (quadriceps or hamstring) and physical functioning
      (chair-stand rate or WOMAC-PF score). CONCLUSION: Varus-valgus laxity is
      associated with a decrease in the magnitude of the relationship between strength
      and physical function in knee OA. In studies examining the functional and
      structural consequences of resistance exercise in knee OA, stratification of
      analyses by varus-valgus laxity should be considered. The effect of strengthening
      interventions in knee OA may be enhanced by consideration of the status of the
      passive restraint system.

PMID- 9920011
TI  - Grip strength and the risk of developing radiographic hand osteoarthritis:
      results from the Framingham Study.
AB  - OBJECTIVE: In knees, quadriceps strength may protect against osteoarthritis (OA).
      Muscle activity is a major determinant of forces at the hand joints, and grip is
      a common task during which high muscle forces are sustained, especially at the
      proximal hand joints (metacarpophalangeal [MCP] joints and thumb base). This
      longitudinal study of radiographic hand OA examined the association between
      incident OA at different hand joints and maximal grip strength. METHODS: Four
      hand joint groups were studied: distal interphalangeal (DIP), proximal
      interphalangeal (PIP), MCP, and the base of the thumb (carpometacarpal and
      scaphotrapezial combined). Subjects were members of the Framingham OA Study who
      had a baseline radiograph in 1967-1969 and a followup radiograph in 1992-1993
      (mean followup 24 years) and had no prevalent radiographic OA in any hand joint
      at baseline. Incident disease was defined as development of OA defined as a
      modified Kellgren/Lawrence grade of > or =2. Grip strength was measured in
      kilograms by dynamometer in 1958-1961 and again in 1960-1963, and the 2 measures
      were averaged and divided into sex-specific tertiles. Joint-based analysis was
      performed by adjusting for age, physical activity, and occupational category
      using the lowest grip strength tertile as the referent. RESULTS: Baseline and
      followup radiographs were obtained from 746 subjects. Of these, 453 subjects with
      no prevalent OA at baseline were eligible for analysis. In men, higher maximal
      grip strength was associated with an increased risk of OA in the PIP (highest
      tertile odds ratio [OR] 2.8 compared with lowest tertile, 95% confidence interval
      [95% CI] 1.2-6.7), MCP (highest tertile OR 2.9, 95% CI 1.1-7.4), and thumb base
      joints (highest tertile OR 2.8, 95% CI 1.1-7.4). In women, there was increased
      risk of OA in the MCP joints (highest tertile OR 2.7, 95% CI 1.1-6.4).
      CONCLUSION: Men with high maximal grip strength are at increased risk for the
      development of OA in the PIP, MCP, and thumb base joints, and women, in the MCP
      joints. No association was found between maximal grip strength and incident OA in
      the DIP joints of men or women.

PMID- 9920012
TI  - Changes in serum cartilage marker levels indicate altered cartilage metabolism in
      families with the osteoarthritis-related type II collagen gene COL2A1 mutation.
AB  - OBJECTIVE: The Arg5l9-Cys mutation in type II collagen results in severe,
      precocious familial osteoarthritis (OA) in 100% of carriers within the first 3
      decades of life. The carrier population provided a well-defined patient
      population for the study of serum markers of familial OA with respect to
      pathogenesis, diagnosis, and prognosis. METHODS: Serum was obtained from 31
      mutation-positive individuals and 16 mutation-negative individuals. OA severity
      was determined by clinical and radiologic assessments. Levels of serum cartilage
      oligomeric matrix protein (COMP), keratan sulfate (KS) epitope, the 846 epitope
      of aggrecan, and the C propeptide of type II collagen (CPII) were measured and
      were correlated with the radiologic findings. RESULTS: COMP and KS levels, both
      of which have been suggested to be indicative of disturbed cartilage turnover,
      were significantly elevated in mutation-positive individuals and in the
      individuals with OA regardless of mutation status. There was no statistically
      significant difference between mutation-positive, mutation-negative, OA-positive,
      and OA-negative individuals with respect to serum concentrations of epitope 846
      or CPII, both of which are putative markers of cartilage repair. CONCLUSION:
      Study of the macromolecular constituents of cartilage released into serum in
      subjects with familial OA revealed altered metabolism in OA, as demonstrated by
      elevated COMP and KS levels. Other constituents, the 846 epitope and CPII, were
      not altered, indicating dissociation of cartilage anabolism and breakdown. Future
      sequential studies will provide an opportunity to define biochemical changes as
      familial OA develops and to monitor therapeutic responses.

PMID- 9920013
TI  - Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992.
AB  - OBJECTIVE: To describe trends in systemic lupus erythematosus (SLE) incidence and
      mortality over the past 4 decades. METHODS: Using the Rochester Epidemiology
      Project resources, medical records were screened to identify all Rochester,
      Minnesota residents with any SLE-associated diagnoses, discoid lupus, positivity
      for antinuclear antibodies, and/or false-positive syphilis test results
      determined between January 1, 1980 and December 31, 1992. Medical records were
      then reviewed using a pretested data collection form in order to identify cases
      of SLE according to the American College of Rheumatology 1982 revised criteria
      for SLE. Drug-induced cases were excluded. All identified SLE patients were
      followed up until death, migration from the county, or October 1, 1997. These
      data were combined with similar data from the same community obtained between
      1950 and 1979, and trends in the SLE incidence and mortality over time were
      calculated. RESULTS: Of the 430 medical records reviewed, 48 newly diagnosed
      cases of SLE (42 women and 6 men) were identified between 1980 and 1992. The
      average incidence rate (age- and sex-adjusted to the 1970 US white population)
      was 5.56 per 100,000 (95% confidence interval [95% CI] 3.93-7.19), compared with
      an incidence of 1.51 (95% CI 0.85-2.17) in the 1950-1979 cohort. The age- and sex
      adjusted prevalence rate as of January 1, 1993 was approximately 1.22 per 1,000
      (95% CI 0.97-1.47). Survival among SLE patients was significantly worse than in
      the general population (P = 0.017 compared with the 1980-1992 cohort, and P <
      0.0001 compared with the 1950-1979 cohort, by log-rank test). Cox proportional
      hazards modeling demonstrated a statistically significant improvement in the
      survival rate over time (P = 0.035). CONCLUSION: Over the past 4 decades, the
      incidence of SLE has nearly tripled, and there has been a statistically
      significant improvement in survival. These findings are likely due to a
      combination of improved recognition of mild disease and better approaches to
      therapy.

PMID- 9920014
TI  - Prevalence and risk factors of carotid plaque in women with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the prevalence of carotid atherosclerosis and associated
      risk factors in women with systemic lupus erythematosus (SLE). METHODS: Carotid
      plaque and intima-media wall thickness (IMT) were measured by B-mode ultrasound
      in women with SLE. Risk factors associated with carotid plaque and IMT were
      determined at the time of the ultrasound scan and included traditional
      cardiovascular risk factors, SLE-specific variables, and inflammation markers.
      RESULTS: The 175 women with SLE were predominantly white (87%), with a mean age
      of 44.9 years (SD 11.5). Twenty-six women (15%) had a previous arterial event (10
      coronary [myocardial infarction or angina], 11 cerebrovascular [stroke or
      transient ischemic attack], and 5 both). The mean +/- SD IMT was 0.71 +/- 0.14
      mm, and 70 women (40%) had focal plaque. Variables significantly associated with
      focal plaque (P < 0.05) included age, duration of lupus, systolic, diastolic, and
      pulse pressure, body mass index, menopausal status, levels of total and low
      density lipoprotein (LDL) cholesterol, fibrinogen and C-reactive protein levels,
      SLE-related disease damage according to the Systemic Lupus International
      Collaborating Clinics (SLICC) damage index (modified to exclude cardiovascular
      parameters), and disease activity as determined by the Systemic Lupus Activity
      Measure. Women with longer duration of prednisone use and a higher cumulative
      dose of prednisone as well as those with prior coronary events were more likely
      to have plaque. In logistic regression models, independent determinants of plaque
      (P < 0.05) were older age, higher systolic blood pressure, higher levels of LDL
      cholesterol, prolonged treatment with prednisone, and a previous coronary event.
      Older age, a previous coronary event, and elevated systolic blood pressure were
      independently associated with increased severity of plaque (P < 0.01). Older age,
      elevated pulse pressure, a previous coronary event, and a higher SLICC disease
      damage score were independently related to increased IMT (P < 0.05). CONCLUSION:
      B-mode ultrasound provides a useful noninvasive technique to assess
      atherosclerosis in women with SLE who are at high risk for cardiovascular
      disease. Potentially modifiable risk factors were found to be associated with the
      vascular disease detected using this method.

PMID- 9920015
TI  - Discrepancy between regional cerebral blood flow and glucose metabolism of the
      brain in systemic lupus erythematosus patients with normal brain magnetic
      resonance imaging findings.
AB  - OBJECTIVE: In this study, 2 updated brain-imaging modalities, technetium-99m
      hexamethylpropylene amine oxime-single-photon-emission computed tomography (HMPAO
      SPECT) and fluorine-18 2-fluoro-2-deoxy-D-glucose-positron emission tomography
      (FDG-PET), were used to simultaneously detect regional cerebral blood flow (rCBF)
      and glucose metabolism of the brain in patients with systemic lupus erythematosus
      (SLE). METHODS: Twenty-five female SLE patients, ages 25-40 years, were enrolled
      in this study and assigned to 1 of 2 groups. Group 1 consisted of 13 patients
      with neuropsychiatric manifestations (7 had major and 6 had minor
      manifestations). Group 2 consisted of 12 patients without neuropsychiatric
      manifestations. Serum levels of anticardiolipin antibodies (aCL) and anti
      ribosomal P antibodies (anti-P) were measured. All patients had normal brain
      magnetic resonance imaging (MRI) findings. Ten healthy female volunteers also
      underwent brain MRI, HMPAO-SPECT, and FDG-PET for comparison. RESULTS: 99mTc
      HMPAO-SPECT revealed hypoperfusion lesions in 11 (44%) of 25 SLE patients,
      including 9 (69%) of the 13 patients in group 1, 7 (100%) of the 7 patients with
      major manifestations, 2 (33%) of the 6 patients with minor manifestations, and 2
      (17%) of the 12 patients in group 2. Parietal lobes were the areas most commonly
      involved. FDG-PET revealed hypometabolism in 7 (54%) of the group 1 patients, 6
      (86%) of the 7 patients with major manifestations, and 1 (17%) of the 6 patients
      with minor manifestations. Temporal lobes were the most commonly involved areas.
      However, no significant hypometabolism brain lesions were found in group 2
      patients. All of the 4 patients with headaches and dizziness or headaches alone
      had normal findings on HMPAO-SPECT and FDG-PET. Nine (36%) of the 25 patients
      were positive for aCL. However, the presence of aCL was not related to
      neuropsychiatric manifestations or to HMPAO-SPECT or FDG-PET findings. Five (20%)
      of the 25 patients had anti-P antibodies and psychosis/depression. CONCLUSION: In
      patients with normal brain MRI findings, decreases in glucose metabolism coupled
      with decreases in rCBF are associated with serious neuropsychiatric SLE (NPSLE)
      presentations, while normal glucose metabolism with decreases in rCBF may be
      found in SLE patients with or without NPSLE.

PMID- 9920016
TI  - Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic
      lupus erythematosus compared with the adult disease.
AB  - OBJECTIVE: To determine the prevalence of anti-ribosomal P (anti-P) proteins in
      several groups of patients with juvenile-onset systemic lupus erythematosus (SLE)
      in comparison with the prevalence in adult SLE. METHODS: Serum samples were
      pooled together from 3 cohorts of patients with juvenile-onset SLE in 3 different
      medical centers and from a miscellaneous group of juvenile-onset SLE patients
      whose samples were sent by regional physicians. Sera were studied for the
      presence of anti-P using 2 assays: Western blot with ribosomes as antigen, and an
      enzyme-linked immunosorbent assay with the COOH-terminal 22 amino acids of the
      ribosomal P protein in a multiantigenic peptide format as antigen. Sera found
      positive by both tests were considered positive for anti-P antibodies. Findings
      from similar studies involving a large cohort of patients with adult-onset SLE
      from Oklahoma City were used for comparison. RESULTS: The prevalence of anti-P
      antibodies in the pooled sample of juvenile-onset SLE sera was 45 of 108, or 42%,
      while in the adult cohort from Oklahoma City, 20 of 260, or 7.7%, were positive
      for anti-P (odds ratio [OR] 9.6, P < 10(-8) by Fisher's exact test). In addition,
      it was shown that 12 of 13 patients with both anti-P and anti-double-stranded DNA
      (anti-dsDNA) in the juvenile SLE cohort had nephritis, while only 8 of 22
      patients without both antibodies were nephritic (OR 21.0, P < 10(-8)). It was
      also shown that in 9 illustrative cases, the levels of anti-P and anti-dsDNA
      antibodies usually varied together and in concordance with the clinical activity
      as measured by the SLE Disease Activity Index (SLEDAI). Finally, anti-P-positive
      and anti-P-negative patients had a similar prevalence of anti-dsDNA, anti-Ro/SSA,
      and anti-La/SSB antibodies, but patients with anti-P had a higher prevalence of
      anti-U1 RNP and anti-Sm (P = 0.041 and P = 0.0385, respectively, by Fisher's
      exact test). CONCLUSION: Antibodies to ribosomal P protein are more prevalent in
      juvenile-onset SLE than in adult-onset SLE. Levels of antibodies to ribosomal P
      protein vary with the clinical disease activity as measured by the SLEDAI, often
      in concordance with the levels of anti-dsDNA. The presence of both anti-P and
      anti-dsDNA antibodies was powerfully associated with nephritis in the cohort of
      patients for whom comprehensive clinical and serologic data were available.

PMID- 9920017
TI  - Comparing self-reported function and work disability in 100 community cases of
      fibromyalgia syndrome versus controls in London, Ontario: the London Fibromyalgia
      Epidemiology Study.
AB  - OBJECTIVE: To compare function and disability in fibromyalgia syndrome (FMS)
      cases in the community versus controls, and to identify variables predicting poor
      function and disability. METHODS: We identified 100 FMS cases, 76 pain controls,
      and 135 general controls in a random survey of 3,395 noninstitutionalized adults.
      RESULTS: FMS cases reported worse function (P < 0.00001), more days in bed (P <
      0.001), and more healthy years of life lost (P < 0.0001). More FMS cases were
      disabled (P < 0.00001) and receiving pensions (P < 0.00001). Risk factors for
      disability included middle age and previous heavy manual labor. Pain, fatigue,
      and weakness were most often claimed to affect the ability to work Variables
      predicting work disability were the Fibromyalgia Impact Questionnaire (FIQ)
      score, a prior diagnosis of FMS, nonrestorative sleep, and past heavy physical
      labor. Variables influencing the FIQ score were the number of major symptoms,
      self-reported health satisfaction, tender point count, and education level.
      CONCLUSION: FMS commonly results in loss of function and work disability.

PMID- 9920018
TI  - Salmonella-triggered reactive arthritis: use of polymerase chain reaction,
      immunocytochemical staining, and gas chromatography-mass spectrometry in the
      detection of bacterial components from synovial fluid.
AB  - OBJECTIVE: To investigate whether microbial components are present in the cells
      of synovial fluid or peripheral blood from patients with Salmonella-triggered
      reactive arthritis (ReA). METHODS: Synovial fluid cells and/or peripheral blood
      cells from 23 patients with Salmonella-triggered ReA and from 19 control patients
      with newly diagnosed rheumatoid arthritis were studied using 3 different
      polymerase chain reaction (PCR) techniques and immunocytochemical staining.
      Muramic acid from the synovial fluid was studied by gas chromatography-mass
      spectrometry. RESULTS: Salmonella chromosomal DNA was not detectable in the
      synovial fluid cells and peripheral blood leukocytes of patients with Salmonella
      ReA. Initially, positive reactions were observed in the synovial fluid cells and
      peripheral blood leukocytes of 3 of 17 and 3 of 18 patients with ReA,
      respectively, but in the subsequent PCR studies, these findings were not
      reproducible. Salmonella-specific antigen was detectable by immunofluorescence in
      the synovial fluid cells and peripheral blood leukocytes of 4 of 11 and 2 of 7
      patients with ReA, respectively. Muramic acid was present in 2 of 15 synovial
      fluid samples from patients with ReA, but the bacterial cultures from synovial
      fluid were negative. CONCLUSION: These findings indicate the presence of
      bacterial degradation products, but not bacterial DNA, in the inflamed joints of
      patients with Salmonella-triggered ReA.

PMID- 9920019
TI  - Amelioration of collagen-induced arthritis and suppression of interferon-gamma,
      interleukin-12, and tumor necrosis factor alpha production by interferon-beta
      gene therapy.
AB  - OBJECTIVE: To investigate the therapeutic effects and possible mechanisms of
      action of constitutive expression of interferon-beta (IFNbeta) by syngeneic
      fibroblasts from DBA/1 mice in the collagen-induced arthritis (CIA) model.
      METHODS: Immortalized embryonic DBA/1 fibroblasts were infected with a retrovirus
      expressing murine IFNbeta. IFNbeta-expressing fibroblasts were then implanted
      intraperitoneally into mice immunized with bovine type II collagen. The effect of
      IFNbeta on paw swelling, anticollagen antibody levels, IgG1/IgG2a isotype
      profiles, arthritis score, histologic joint damage, and cytokine secretion from
      lymph node cells and from bone marrow-derived macrophages was assessed. RESULTS:
      A single injection of IFNbeta-secreting fibroblasts was sufficient to prevent
      arthritis or to ameliorate existing disease. Thus, IFNbeta reduced the clinical
      score and paw swelling irrespective of whether the injection was administered
      before or after disease onset in treated mice, compared with that in the
      untreated control group (P < 0.05). Histologic findings in the IFNbeta-treated
      mice were markedly less severe than in the control group (P < 0.001). This effect
      was accompanied by a decrease in total anticollagen IgG levels, a decrease in
      anticollagen IgG2a, and an increase in IgG1. In vitro, supernatants from these
      engineered fibroblasts inhibited collagen-induced interferon-gamma secretion from
      lymph node cells, and reduced the levels of tumor necrosis factor alpha and
      interleukin-12 produced by lipopolysaccharide/IFNgamma-treated bone marrow
      derived macrophages. This effect was specific, since it was reversed with anti
      IFNbeta polyclonal antibodies. CONCLUSION: These results indicate that IFNbeta,
      which is currently used as a treatment for relapsing, remitting multiple
      sclerosis, is a potent immunomodulatory and antiinflammatory cytokine in CIA and
      should be considered for the treatment of rheumatoid arthritis.

PMID- 9920020
TI  - Biphasic regulation of the development of murine type II collagen-induced
      arthritis by interleukin-12: possible involvement of endogenous interleukin-10
      and tumor necrosis factor alpha.
AB  - OBJECTIVE: To examine the dose-specific effects of interleukin-12 (IL-12) on the
      evolution of murine type II collagen-induced arthritis (CIA). METHODS: From day
      24 through day 33 following primary immunization, mice received daily
      intraperitoneal injections of murine recombinant IL-12. Measurements of
      anticollagen IgG, cytokines, and corticosterone were performed using enzyme
      linked immunosorbent assay and radioimmunoassay. RESULTS: CIA mice injected with
      a low dose of IL-12 (5 ng/day) exhibited accelerated onset and increased severity
      of arthritis. In contrast, administration of a high dose of IL-12 (500 ng/day)
      attenuated arthritic inflammation. The low dose of IL-12 induced tumor necrosis
      factor alpha (TNFalpha) production, whereas the high dose induced production of
      both IL-10 and corticosterone and suppression of anticollagen antibody levels.
      Administration of neutralizing anti-TNFalpha and anti-IL-10 antibodies reversed
      the dose-specific effects of IL-12. CONCLUSION: IL-12 is an important
      immunomodulator during the pathogenesis of CIA. It appears to act by regulating
      humoral and cellular immune responses, as well as by mediating the expression of
      immunoregulatory cytokines and glucocorticoids.

PMID- 9920021
TI  - Modulation by cytokines of induction of oral tolerance to type II collagen.
AB  - OBJECTIVE: To determine whether the simultaneous administration of drugs and/or
      cytokines such as transforming growth factor beta (TGFbeta) can render oral
      tolerance to type II collagen (CII) more effective in causing resistance to
      collagen-induced arthritis (CIA) in mice, and to investigate whether oral
      tolerance can still be induced when high levels of anti-CII are present. METHODS:
      Tolerance was induced by intragastric feeding of low-dose CII to DBA/1 mice
      during a 2-week period, either before immunization with CII in Freund's complete
      adjuvant or after initiation of arthritis. Some mice were simultaneously injected
      with TGFbeta1 or with the H2 receptor agonist dimaprit. RESULTS: Both TGFbeta1
      and dimaprit increased the degree of oral tolerance obtained. TGFbeta1 augmented
      the induction of immunoregulatory CD8 T cells, which transferred the resistance
      to CIA induction to normal recipients. Feeding of CII for 2 weeks, starting after
      the onset of arthritis, still significantly ameliorated the course of CIA.
      CONCLUSION: Administration of TGFbeta1 or dimaprit, both of which are believed to
      promote the development of immunoregulatory T cells, may reinforce induction of
      oral tolerance, even after the onset of arthritis.

PMID- 9920022
TI  - High-resolution three-dimensional magnetic resonance imaging for the
      investigation of knee joint damage during the time course of antigen-induced
      arthritis in rabbits.
AB  - OBJECTIVE: To investigate the efficacy of high-resolution 3-dimensional magnetic
      resonance imaging (3-D MRI) with gadolinium contrast agent enhancement in
      monitoring soft tissue and hard tissue changes during the course of antigen
      induced arthritis in rabbits, comparing the images with the final histologic
      outcome. METHODS: Arthritis was induced by intraarticular injection of methylated
      bovine serum albumin into rabbits that had been presensitized to the same
      antigen. MRI was carried out before and on predetermined days after the onset of
      inflammatory arthritis, up to day 60. At each time point, 3-D gradient-echo
      images were acquired. At the end of the study, the knee joints were processed for
      histologic study. RESULTS: Time-related inflammatory changes, such as soft tissue
      swelling, were seen initially, followed by a reduction in the acute swelling and
      a progression to hard tissue damage at later time points. The final 3-D data sets
      were then used to compare MR images with the histologic sections. The knee joints
      were sectioned in the sagittal, coronal, or transverse direction. Comparison of
      final images and histologic features at day 60 enabled a more complete
      interpretation of the MR images, allowing direct correlation of joint damage
      observed using the MRI technique with that seen in the final histologic analysis.
      CONCLUSION: Qualitative information derived from MR images correlated extremely
      well with histologic findings. These results indicate the great potential of MRI
      for noninvasive investigation of drug effects in this model of arthritis.

PMID- 9920023
TI  - Relationship of matrix metalloproteinases and their inhibitors to cartilage
      proteoglycan and collagen turnover: analyses of synovial fluid from patients with
      osteoarthritis.
AB  - OBJECTIVE: To determine the relationship between matrix metalloproteinases
      (MMPs), their inhibitors, and the turnover of matrix molecules in articular
      cartilage from patients with osteoarthritis (OA). METHODS: Synovial fluid samples
      were collected from the knees of 54 patients with OA. Radiographic evaluations
      and magnetic resonance imaging were performed on the knees of 34 OA patients to
      classify the stage of the disease. Biochemical analyses and immunoassays were
      used to measure the concentrations of MMP-1, MMP-3, tissue inhibitor of
      metalloproteinases 1 (TIMP-1), TIMP-2, the disaccharide of hyaluronic acid, the
      proteoglycan glycosaminoglycan disaccharides of chondroitin 4-sulfate (delta di
      CS4) and chondroitin 6-sulfate (delta di-CS6), the 846 epitope on chondroitin
      sulfate of cartilage proteoglycan aggrecan (putative biosynthetic marker), the
      keratan sulfate (KS) epitope of aggrecan (putative degradation marker), and the C
      propeptide of cartilage type II procollagen (CPII) (biosynthetic marker).
      RESULTS: The concentration of TIMP-1 was directly correlated with the levels of
      MMP-1 and MMP-3 (both were also correlated with each other), confirming earlier
      results. There was an inverse correlation between the delta di-CS6:delta di-CS4
      ratio and the concentration of MMP-3. The level of delta di-CS6 was correlated
      with that of the KS epitope, and to a lesser degree, with that of the 846 epitope
      (the latter was also correlated with the level of delta di-CS4). The
      concentration of TIMP-1 correlated with that of the 846 epitope, whereas TIMP-2
      levels correlated with those of CPII. There were significantly lower
      concentrations of delta di-CS6, delta di-CS4, the 846 epitope, and CPII in
      synovial fluid from patients with late-stage OA. CONCLUSION: These observations
      suggest a link between proteolysis and inhibitor concentrations in OA cartilage.
      Production of TIMPs appears to be individually linked to the synthesis of
      specific cartilage molecules. The reduction in the amount of cartilage-matrix
      structural components suggests that there is a measurable loss of cartilage in
      the late stages of the disease, as suggested previously. The resultant
      composition of the cartilage suggests that the loss may primarily involve
      "resident" molecules originally present in healthy cartilage.

PMID- 9920024
TI  - Retinoic acid-induced type II collagen degradation does not correlate with matrix
      metalloproteinase activity in cartilage explant cultures.
AB  - OBJECTIVE: To determine the role of matrix metalloproteinases (MMPs) in retinoic
      acid (RetA)-induced degradation of type II collagen in cartilage. METHODS: Bovine
      nasal cartilage explants were cultured with 1 microM RetA or in 3 nM interleukin
      1alpha (IL-1alpha). Release of proteoglycan and type II collagen into the medium
      was measured by colorimetric assay and immunoassay, respectively. MMP activity in
      the medium was determined using a quenched fluorescent substrate assay, while
      specific collagenases were identified by Western immunoblotting. In some cases
      the effects of low molecular mass synthetic MMP inhibitors and serum on collagen
      degradation were studied. RESULTS: RetA promoted maximal breakdown of type II
      collagen after 4 or 5 weeks in culture, compared with 3 weeks in culture with IL
      1alpha. In IL-1alpha-stimulated cultures, collagen degradation was coincident
      with a large increase in MMP activity in the culture medium, whereas in RetA
      stimulated cultures, there was only a small increase. In Western immunoblots of
      culture media containing RetA, prointerstitial collagenase and active collagenase
      3 were sometimes detected, but not in all experiments. In IL-1alpha cultures,
      active interstitial collagenase was always detected, and active collagenase 3 was
      detectable in some experiments. Neutrophil collagenase was not detected in any
      cultures. IL-1alpha-stimulated collagen degradation was effectively inhibited by
      a potent, broad-spectrum inhibitor of MMPs, whereas it was poorly inhibited by a
      weak MMP inhibitor. The same 2 compounds were both only weak inhibitors of RetA
      induced collagen degradation. When fetal calf serum was included in cartilage
      cultures, MMP activity in the culture medium was reduced to low levels. This
      resulted in a marked inhibition of IL-1alpha-induced type II collagen
      degradation, whereas there was no inhibition of RetA-induced collagen
      degradation. CONCLUSION: Unlike IL-1alpha, RetA induces degradation of type II
      collagen in cartilage explants by a mechanism that is mainly independent of those
      MMPs that can be detected in the culture medium.

PMID- 9920025
TI  - Avocado/soya unsaponifiables enhance the expression of transforming growth factor
      beta1 and beta2 in cultured articular chondrocytes.
AB  - OBJECTIVE: Avocado and soya unsaponifiables (ASU) have been reported to exert
      beneficial effects in the treatment of periodontal and osteoarticular diseases.
      They are supposed to stimulate deposition and repair of extracellular matrix
      components, but the mechanisms underlying their action are not well understood.
      In view of the repair potential of osteoarthritic (OA) cartilage and the role
      that the transforming growth factor beta (TGFbeta) system could play in that
      process, we carried out in vitro studies to determine the mechanism of action of
      ASU on articular chondrocytes that may account for the beneficial effects on
      cartilage metabolism. METHODS: Cultured bovine articular chondrocytes were
      treated with various concentrations of ASU, and the expression of both TGFbeta
      isoforms, 1 and 2, and their receptors (TGFbetaRI and TGFbetaRII) was determined
      by Northern blot and reverse transcriptase-polymerase chain reaction. Cell
      transfection with TGFbeta1 promoter constructs was also used to delineate the cis
      acting sequences mediating ASU responsiveness in chondrocytes. The level of
      plasminogen activator inhibitor 1 (PAI-1) was also evaluated by Northern blotting
      and protein radiolabeling. RESULTS: The data indicated that ASU stimulate the
      expression of TGFbeta1, TGFbeta2, and PAI-1 by articular chondrocytes. In
      contrast, the levels of TGFbetaRI and TGFbetaRII were not significantly affected
      by the compound. Treatment of bovine articular chondrocytes transiently
      transfected with TGFbeta1 promoter constructs suggested that the effect on
      TGFbeta1 expression is mediated by the region located between -732 and -1132 bp.
      CONCLUSION: The results indicate that the ASU-induced stimulation of matrix
      synthesis previously reported in cultured articular chondrocytes could be
      explained by the ability to enhance TGFbeta expression in these cells. Further,
      ASU increase the production of PAI-1, an effect that could help in blocking the
      plasmin cascade that leads to metalloprotease activation. These data suggest that
      the compound has properties that might promote TGFbeta-induced matrix repair
      mechanisms in articular cartilage.

PMID- 9920026
TI  - Enhancement of phosphorylation and transcriptional activity of the glucocorticoid
      receptor in human synovial fibroblasts by nimesulide, a preferential
      cyclooxygenase 2 inhibitor.
AB  - OBJECTIVE: To examine the effect of 2 nonsteroidal antiinflammatory drugs
      (NSAIDs), nimesulide (NIM), a preferential cyclooxygenase 2 (COX-2) inhibitor,
      and naproxen (NAP), on the functional parameters and transcriptional activity of
      the glucocorticoid receptor (GR) system in cultured human synovial fibroblasts
      (HSF). METHODS: HSF were incubated with NIM (0.3, 3, and 30 microg/ml), NAP (15,
      30, and 90 microg/ml), and dexamethasone (DEX; 0.01, 0.1, and 1 microM) on a time
      and dose-dependent basis. The numbers of GR binding sites per cell were
      determined by radioligand receptor assay. Total cellular, cytoplasmic, or nuclear
      GR protein was measured by Western analysis using a specific anti-human GR
      antibody. Phosphorylation of GR was determined by specific immunoprecipitation of
      protein extracts from 32P-orthophosphate-labeled HSF. Mitogen-activated protein
      kinase p44/42 (MAPK) phosphorylation was followed by Western analysis using a
      specific anti-phosphoMAPK antibody. Levels of activated nuclear GR capable of
      binding specifically to a 32P-labeled oligonucleotide harboring the
      glucocorticoid/hormone response element (GRE) were evaluated by gel
      electrophoretic mobility shift analysis. The effects of NIM and DEX on
      transcriptional activation of the mouse mammary tumor virus (MMTV) promoter was
      determined by transfecting HSF with MMTV-luciferase (reporter gene) constructs.
      RESULTS: NIM had no effect on the number of GR binding sites, in contrast to NAP
      and DEX. NIM and NAP did not influence cellular GR protein levels or
      nucleocytoplasmic shuttling, although DEX lowered GR messenger RNA and protein
      levels after 48 hours. NIM, but not NAP, markedly increased MAPK phosphorylation
      (suggesting an increase in MAPK cascade activity), GR phosphorylation, GR binding
      to GRE, and transcriptional activation of MMTV promoter through the GRE site in
      the promoter. CONCLUSION: This study is the first to report that the
      antiinflammatory effects of NIM, an NSAID, may be partly related to its
      activation of the GR system.

PMID- 9920027
TI  - Beta2-glycoprotein I is necessary to inhibit protein C activity by monoclonal
      anticardiolipin antibodies.
AB  - OBJECTIVE: To clarify mechanisms of the thrombosis associated with
      anticardiolipin antibodies (aCL), we examined the effects on activated protein C
      (APC) of monoclonal aCL and beta2-glycoprotein I (beta2GPI), which is required
      for formation of the epitopes of aCL. METHODS: We developed the chromogenic
      assay, in which the degradation of coagulation factor Va by APC is reflected in
      the reduced generation of thrombin from prothrombin, using soybean trypsin
      inhibitor to inhibit APC. APC activities were measured in the presence and
      absence of 3.4 microM beta2GPI and/or 2.5 microg/ml of IgM monoclonal aCL (EY2C9
      and EY1C8) established from peripheral blood lymphocytes obtained from a patient
      with aCL. RESULTS: Without APC, the formed thrombin activity decreased by the
      addition of 3.4 microM beta2GPI. When 12.8 nM APC was added, beta2GPI partially
      reversed the APC-induced inhibition of thrombin generation in a concentration
      dependent manner. With 3.4 microM beta2GPI, the thrombin generation in monoclonal
      aCL (2.5 microg/ml) decreased to 77.1-80.2% by the addition of 12.8 nM APC, but
      the values were above that in the control IgM (72.7%). Without beta2GPI, the APC
      activity was unaffected by the addition of monoclonal aCL. CONCLUSION: Beta2
      glycoprotein I exhibits procoagulant activity by inhibiting APC activity and
      anticoagulant activity by inhibiting thrombin generation. Any further inhibition
      of APC activity was caused by monoclonal aCL and only in the presence of
      beta2GPI.

PMID- 9920028
TI  - Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role
      of peptide supermotif in the pathogenesis of spondylarthropathies.
AB  - OBJECTIVE: Previous studies indicated the increase of HLA-B39 among HLA-B27
      negative patients with spondylarthropathies (SpA). This study was performed to
      examine whether the natural ligands of HLA-B27 are capable of binding to HLA-B39.
      METHODS: Peptides were synthesized according to the sequences of known natural
      ligands of HLA-B27 or B39 and were tested for their binding to HLA-B*3901 and
      B*2705 by quantitative peptide binding assay, using a TAP-deficient RMA-S cell
      line transfected with human beta2-microglobulin and HLA class I heavy chain
      genes. RESULTS: Four of the 10 HLA-B27 binding peptides significantly bound to
      HLA-B*3901. All 4 peptides had hydrophobic/aromatic amino acids (Leu or Phe) at
      the C-terminus. In contrast, peptides with basic residues (Lys, Arg) or Tyr at
      the C-terminus did not bind to B*3901. In parallel experiments, 1 of the 2
      natural ligands of HLA-B*3901 was found to bind to B*2705. CONCLUSION: A subset
      of natural HLA-B27 ligands was capable of binding to B*3901. In addition to Arg
      at position 2 (Arg2), hydrophobic/aromatic C-terminal residues, such as Leu or
      Phe, seemed to be crucial for the cross-specificity. These results suggested that
      HLA-B27 and B39 recognize overlapping peptide repertoires, supporting the
      hypothesis that the peptides presented by both of these class I antigens play a
      role in the pathogenesis of SpA.

PMID- 9920029
TI  - Localized bowel vasculitis: postoperative cyclophosphamide or not?
AB  - We describe 2 patients with necrotizing vasculitis localized to the bowel, who
      were treated by excision of the involved tissue. Postoperatively, there was no
      evidence of active vasculitis, and both patients remain in remission on followup,
      without the use of immunosuppressive treatment. Evidence that an abnormal local
      microenvironment is necessary to sustain chronic inflammation may explain why
      surgical excision can be an important tool in the treatment of vasculitis.

PMID- 9920030
TI  - Induction therapy with an intravenous loading dose of azathioprine for treatment
      of refractory, active rheumatoid arthritis.

PMID- 9920031
TI  - Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody-negative
      patients.

PMID- 9920032
TI  - Does early and aggressive treatment improve the prognosis in psoriatic arthritis?
      Comment on the article by Wong et al.

PMID- 9920033
TI  - Acute-phase response and risk of developing ischemic complications in giant cell
      arteritis: comment on the article by Cid et al.

PMID- 9920035
TI  - Naming names! Comment on the article by Smolen and Steiner.

PMID- 9920034
TI  - Clinical, immunologic, and immunogenetic evidence that mixed connective tissue
      disease is a distinct entity: comment on the article by Smolen and Steiner.

PMID- 9920036
TI  - Iloprost treatment in systemic sclerosis: comment on the concise communication by
      Tedeschi et al.

PMID- 9920038
TI  - Trypanosoma cruzi: protective response of vaccinated mice is mediated by CD8+
      cells, prevents signs of polyclonal T lymphocyte activation, and allows
      restoration of a resting immune state after challenge.
AB  - Currently, there is no vaccine available against Chagas' disease. Immune
      abnormalities induced by T. cruzi pose particular difficulties for vaccine
      development, since immunological memory must be able to overcome them to prevent
      spread of infection/sequelae. We have previously demonstrated that experimental
      vaccination with live CL-14 trypomastigotes does not induce polyclonal lymphocyte
      activation, immunosuppression, or pathology and efficiently immunizes against
      virulent T. cruzi. Herein we show that: (1) expansion of CD4+ and CD8+ subsets
      peaks 2 weeks after infective challenge in both challenged-vaccinated mice and
      infected controls, but the former exhibit a smaller increase in blastogenesis and
      in the numbers of activated CD11a(hi)CD4+ and CD11a(hi)CD8+ cells; (2) in long
      term-vaccinated mice, expansion of activated subsets (CD62Llo/- and CD11a(hi)) is
      accelerated among CD8+ PBL 1 week after challenge; (3) challenged-vaccinated mice
      retract the CD8+-activated subset 5 weeks after challenge, different from
      infected controls; (4) protection conferred by CL-14 immunization can be
      adoptively transferred to naive recipients with lymphocyte suspensions, and prior
      depletion of CD8+ (but not of CD4+) cells abolishes protective immunity. Our
      findings indicate that protective immunity generated by CL-14 immunization
      involves a transient CD8+ recall response and is capable of preventing the signs
      of polyclonal lymphocyte activation induced by virulent challenge.

PMID- 9920037
TI  - Onchocerca volvulus: immunolocalization of the extracellular CuZn superoxide
      dismutase using antibodies raised against a 15-mer epitope of this enzyme.
AB  - The study describes the immunohistological localization of the extracellular CuZn
      superoxide dismutase (SOD2) in the parasitic nematode Onchocerca volvulus. Using
      specific antiserum raised against a 15-amino-acid peptide from the N-terminal
      region of the mature protein, this enzyme is detected primarily in the intestinal
      epithelium of the adult worms and to a lesser extent in the muscle cells of the
      uterine wall. A blocking experiment with the SOD2 peptide reduced the staining
      significantly, confirming specificity. The localization profile of SOD2
      correlates extremely well with the localization of iron deposits in the gut and
      uterine muscle cells of adult O. volvulus. The detection of SOD2 in the
      functional intestine of O. volvulus, together with the evidence that it is a
      secreted protein, indicates that this enzyme in parasitic nematodes is in a
      position to interact with host molecules. It also demonstrates the accessibility
      of the parasite enzyme to an inhibitor or blocking antibody.

PMID- 9920039
TI  - Schistosoma mansoni: in vitro adhesion of parasite eggs to the vascular
      endothelium. Subsequent inhibition by a monoclonal antibody directed to a
      carbohydrate epitope.
AB  - Schistosoma mansoni eggs come into direct contact with the vascular endothelium,
      particularly in the postcapillary venules of the mesenteric tract (oviposition
      site). We investigated the adhesion of eggs to endothelial cells in a static in
      vitro assay and in a flow-based in vitro assay. Live S. mansoni eggs rapidly
      attached, in a time-dependent manner, to the human endothelial cell line ECV 304,
      but not KOH-treated eggs. Activation of ECV monolayers with interleukin-1
      promoted live S. mansoni eggs adhesion. An in vitro flow-based assay of human
      umbilical vein endothelial cells (HUVEC) showed the influence of wall shear
      stresses on the attachment of eggs to endothelial cells, particularly under
      postcapillary venule shear stress conditions. Interleukin-1 activation of HUVEC
      promoted adhesion between live eggs and endothelial cells. Higher wall shear
      stresses were needed to obtain the detachment of eggs from activated endothelial
      cells than control cells. Preincubation of interleukin-1-activated HUVEC, in a
      static in vitro assay, with monoclonal antibodies specific for intercellular
      adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1
      significantly decreased adhesion of live eggs. Previous studies have shown that a
      monoclonal antibody specific for a schistosome carbohydrate epitope abundant in
      eggs is related to the Lewis X antigen. In this study, the anti-Lewis X-specific
      monoclonal antibody was used for adhesion-inhibition assays. Preincubation of
      eggs with this monoclonal antibody significantly decreased adhesion of live eggs
      to interleukin-1-activated HUVEC cultured in vitro. These results suggest that
      surface adhesion molecules, expressed by endothelial cells under conditions of
      interleukin-1 activation, directly participate in egg adhesion and that egg
      carbohydrate antigens play an important role in live S. mansoni egg adhesion to
      the vascular endothelium.

PMID- 9920040
TI  - Plasmodium coatneyi: differential clinical and immune responses of two
      populations of Macaca fascicularis from different origins.
AB  - Two species of macaques, including two Macaca fascicularis from the Philippines,
      two M. fascicularis from Mauritius, and one Macaca mulatta, were experimentally
      infected with blood stages of Plasmodium coatneyi and followed during their
      clinical, parasitological, biological, and immunological evolution. Plasma
      cytokine (TNF-alpha, IL-1beta, IL-6, IFN-gamma) production peaked for all monkeys
      11 days after inoculation, concomitantly with peaks of parasitemia. Only the M.
      fascicularis from the Philippines survived the infection. The main features,
      which discriminated nonfatal from fatal cases, were the observation in M.
      fascicularis from the Philippines of a mean CD4+/CD8+ ratio below I and of their
      ability, as revealed by mitogenic stimulation of whole blood, to produce
      increasing amounts of IFN-gamma as infection evolved. The contribution of
      environmental and genetic factors, which may differentiate the three groups of
      monkeys and therefore explain fatal or nonfatal evolution of the infection among
      them, is discussed.

PMID- 9920041
TI  - Babesia bovis: common protein fractions recognized by oligoclonal B. bovis
      specific CD4+ T cell lines from genetically diverse cattle.
AB  - CD4+ helper T cells are believed to be important for inducing protective immunity
      against Babesia bovis through the production of cytokines, including IFN-gamma,
      that will provide help to B lymphocytes for IgG production and activate
      macrophages to become parasiticidal. To provide maximum protection in an outbred
      population, an effective vaccine against B. bovis should contain antigens that
      would elicit an IFN-gamma response and would be recognized by cattle with diverse
      genetic backgrounds. To identify potentially protective "universal" T helper (Th)
      cell antigens, fractions of homogenized B. bovis merozoites were tested for the
      ability to stimulate proliferation of oligoclonal CD4+, IFN-gamma-producing T
      cell lines derived from four immune animals previously shown to differ in major
      histocompatibility complex class II expression. Homogenized B. bovis merozoites
      were separated by denaturing continuous flow electrophoresis (CFE) on 15, 10, and
      7.5% polyacrylamide gels into fractions containing proteins ranging from <14.5 to
      approximately 95 kDa. Eighteen of 280 CFE fractions elicited anamnestic
      proliferative responses in all T cell lines tested. Nine of these cross
      stimulatory fractions contained proteins of <14.5 to 24.5 kDa, and the remaining
      ones contained proteins with estimated molecular weights of 30, 31.5, 44.5, 49,
      49.5, 54, 62, 72, and 82 kDa. Immunoblot analysis showed that four cross
      stimulatory fractions contained a predicted known B. bovis antigen of similar
      molecular size. Previous studies had demonstrated that fractionated merozoite
      proteins stimulatory for CD4+ Th cell clones had apparent molecular weights
      similar to those present in 7 of the 18 stimulatory fractions. In the present
      study, two Th cell clones responded to cross-stimulatory CFE fractions,
      underscoring the potential to use both oligoclonal and monoclonal Th cell lines
      to identify commonly recognized polypeptides as potential vaccine antigens.

PMID- 9920042
TI  - Hymenolepis diminuta: catalysis of transmembrane proton translocation by
      mitochondrial NADPH-->NAD transhydrogenase.
AB  - The mitochondrial, inner-membrane-associated, reversible NADPH-->NAD
      transhydrogenase of adult Hymenolepis diminuta physiologically couples matrix
      localized, NADP-specific "malic" enzyme with NADH-dependent anaerobic electron
      transport. Employing submitochondrial particles (SMP) as the source of enzyme
      activity and both spectrophotometric and fluorometric assessments, the present
      study made evident that in its catalysis of transhydrogenation between NADPH and
      NAD, the cestode enzyme engages in the concomitant transmembrane translocation of
      protons. As assessed spectrophotometrically, the catalysis of NADPH-dependent NAD
      reduction by H. diminuta SMP was stimulated significantly by carbonyl cyanide 3
      chlorophenylhydrazone (CCCP), carbonyl cyanide 4-(trifluoromethoxy)
      phenylhydrazone (FCCP), as well as by the protonophoric anthelmintic,
      niclosamide. In addition, N,N'-dicyclohexylcarbodiimide (DCCD) markedly
      diminished SMP-catalyzed hydride ion transfer between NADPH and NAD. The
      catalysis by SMP of concomitant, transhydrogenase-mediated proton translocation
      was evaluated more directly via fluorometric assays using 8-anilino-1
      napthalenesulfonic acid (ANS) as the probe. These latter evaluations revealed a
      transhydrogenase-dependent enhancement of ANS fluorescence in accord with an
      intravesicular accumulation of protons. ANS fluorescence was quenched rapidly
      when the assay system was supplemented with CCCP, FCCP, or niclosamide.
      Consistent with the helminth transhydrogenase acting as a proton pump,
      transhydrogenase-mediated enhanced fluorescence also was inhibited by DCCD.
      Considered collectively, these data indicated, apparently for the first time for
      any invertebrate system, that the transhydrogenase, in catalyzing the NADPH-->NAD
      reaction, acts in the translocation of protons from the matrix to the
      intermembrane space mitochondrial compartment.

PMID- 9920044
TI  - Leishmania: identification of Old World species using a permissively primed
      intergenic polymorphic-polymerase chain reaction.
AB  - We have developed a permissively primed intergenic polymorphic-polymerase chain
      reaction (PPIP-PCR) which distinguishes between the Old World Leishmania
      complexes L. major, L. tropica, L. donovani, and L. aethiopica. This technique
      pairs one parasite-specific and one nonspecific oligonucleotide primer for the
      PCR. The specific primer was chosen from a unique leishmanial DNA sequence, clone
      pDOG 2, isolated from a L. donovani chagasi genomic DNA expression library. This
      sequence has a high DNA homology to the intergenic region of the L. major B/C
      genes which belong to the polymorphic LmcDNA16 gene family. The specific
      intergenic primer contains a high GC content, a stem-loop, and a 3'-CG residue.
      The nonspecific primer was selected from within the pBluescript (SK) plasmid.
      Using PPIP-PCR, parasites belonging to the L. major, L. tropica, L. donovani, and
      L. aethiopica complexes could be easily identified directly following agarose gel
      electrophoresis by the simple profiles of their PCR products. In addition, it was
      possible to discriminate between strains of L. major or L. donovani from distant
      geographical regions. Amplification of genomic DNA isolated from several
      nonleishmanial kinetoplastids yielded either no PCR products or unique bands
      which were distinct from the leishmanial profiles. Genomic DNA from
      nonkinetoplastid parasites, plants, or mammals was not amplified by PPIP-PCR.
      This technique is a rapid and reproducible method for the characterization of Old
      World Leishmania.

PMID- 9920043
TI  - Mosquito-Plasmodium interactions in response to immune activation of the vector.
AB  - During the development of Plasmodium sp. within the mosquito midgut, the parasite
      undergoes a series of developmental changes. The elongated ookinete migrates
      through the layers of the midgut where it forms the oocyst under the basal
      lamina. We demonstrate here that if Aedes aegypti or Anopheles gambiae, normally
      susceptible to Plasmodium gallinaceum and P. berghei, respectively, are immune
      activated by the injection of bacteria into the hemocoel, and subsequently are
      fed on an infectious bloodmeal, there is a significant reduction in the
      prevalence and mean intensity of infection of oocysts on the midgut. Only those
      mosquitoes immune activated prior to, or immediately after, parasite ingestion
      exhibit this reduction in parasite development. Mosquitoes immune activated 2-5
      days after bloodfeeding show no differences in parasite burdens compared with
      naive controls. Northern analyses reveal that transcriptional activity for
      mosquito defensins is not detected in the whole bodies of Ae. aegypti from 4 h to
      10 days after ingesting P. gallinaceum, suggesting that parasite ingestion,
      passage from the food bolus through the midgut, oocyst formation, and subsequent
      release of sporozoites into the hemolymph do not induce the production of
      defensin. However, reverse transcriptase-PCR of RNA isolated solely from the
      midguts of Ae. aegypti indicates that transcription of mosquito defensins occurs
      in the midguts of naive mosquitoes and those ingesting an infectious or
      noninfectious bloodmeal. Bacteria-challenged Ae. aegypti showed high levels of
      mature defensin in the hemolymph that correlate with a lower prevalence and mean
      intensity of infection with oocysts. Because few oocysts were found on the midgut
      of immune-activated mosquitoes, the data suggest that some factor, induced by
      bacterial challenge, kills the parasite at a preoocyst stage.

PMID- 9920045
TI  - Plasmodium: immunization with carboxyl-terminal regions of MSP-1 protects against
      homologous but not heterologous blood-stage parasite challenge.
AB  - A leading candidate for a vaccine targeted at the erythrocytic stages of
      plasmodial parasite development is the merozoite surface protein-1 (MSP-1). We
      have previously shown that the carboxyl-terminal region of MSP-1 derived from
      Plasmodium yoelii yoelii 17XL, expressed as a fusion protein with glutathione S
      transferase (GST-PYC2), can immunize mice against an otherwise lethal homologous
      challenge infection. This protection has been shown to be predominantly mediated
      by antibodies. We report here on the efficacy of immunization with MSP-1 carboxyl
      regions when the challenge is a heterologous rodent parasite species. The course
      of parasitemia was not altered in mice immunized with GST-PYC2 and challenged
      with 10(4) heterologous Plasmodium chabaudi adami parasites, as both control and
      immunized mice developed infections that peaked at day 7 and then rapidly
      declined. Similarly, mice immunized with GST-PYC2 and challenged with 10(5)
      Plasmodium berghei ANKA parasites displayed virulence similar to that seen in
      infection control mice. The homologous region of the P. chabaudi adami MSP-1 gene
      was similarly expressed as a fusion protein with GST. Mice immunized with GST
      PCC2 and challenged with 10(4) parasites showed significant protection against
      homologous P. chabaudi adami infection but no protection whatsoever against
      heterologous P. yoelii yoelii 17XL infection. These in vivo results correlate
      with the observation that sera generated by immunization with the carboxyl region
      of MSP-1 recognizes this protein from homologous, but not heterologous,
      radiolabeled parasite protein preparations.

PMID- 9920046
TI  - Plasmodium berghei: identification of an mdr-like gene associated with drug
      resistance.
AB  - Amplification, mutations, or overexpression of the pfmdr1 gene have been
      associated with multiple drug resistance in some strains of Plasmodium
      falciparum. In order to better understand this potential mechanism of drug
      resistance, we are currently investigating putative mdr homologues in vivo in the
      rodent malaria Plasmodium berghei. We have identified and partially sequenced a
      gene that is amplified in a MFQ-resistant (MFQr) line. Using degenerate primers,
      a 579-bp fragment was amplified by PCR using P. berghei genomic DNA as template.
      The predicted amino acid sequence shares 66% identity with the previously
      reported pfmdr1 gene product (Pgh1) of P. falciparum. Southern blots and slot
      blots of genomic DNA suggest that this gene is amplified two- to threefold in a
      MFQr line (N/1100), as has been previously reported in some MFQr strains of P.
      falciparum. The P. berghei gene was mapped to chromosome 12 in all of the lines
      analyzed. Furthermore, the cloned PCR product also hybridizes to chromosome 5 of
      the MFQr strain.

PMID- 9920047
TI  - Plasmodium berghei and Plasmodium yoelii: molecular karyotypes of drug-resistant
      lines.

PMID- 9920048
TI  - Plasmodium chabaudi chabaudi: a monoclonal antibody raised against soluble
      antigens present in the plasma of infected mice recognizes a 250-kDa schizont
      glycoprotein that is secreted during schizogony.

PMID- 9920049
TI  - Plasmodium falciparum: infectivity of cultured, synchronized gametocytes to
      mosquitoes.

PMID- 9920050
TI  - Polymorphisms in the human DNA ligase I gene (LIG1) including a complex GT
      repeat.
AB  - Sequencing of a human DNA ligase I cDNA clone derived from HeLa cells revealed
      two unreported differences with the published sequence: a single base change and
      a three-base deletion. Both differences are in exon 6, and were analyzed by
      amplifying a segment containing exon 5, intron 6, and exon 6. The first finding
      was that intron 6 is approximately 2.6 kb in size, not the 1 kb reported in the
      literature. By sequence analysis of amplified segments, the single-base
      difference in exon 6 was shown to be polymorphic, with HeLa cells heterozygous
      for the A/C difference. Analysis of 60 unrelated individuals found a frequency of
      0.5 for each allele. Primer extension reactions across the exon 5/exon 6 boundary
      were performed on cDNA obtained from HeLa cells and human thymus. The results
      show that the three-base deletion is due to a variation in splicing. For both
      HeLa and thymus, two-thirds of the transcripts are like the published cDNA
      sequence and one-third have the three-base deletion. Finally, sequencing of part
      of intron 6 revealed the presence of a complex GT repeat consisting of a 48-50
      nucleotide polypurine tract followed by a variable number of GT residues. This
      entire unit of polypurine tract plus GTs is repeated three times. Detection of
      the repeated sequences required the development of specialized cloning and PCR
      conditions. Analysis of a pedigree showed that this complex repeat is
      polymorphic.

PMID- 9920051
TI  - Trinucleotide repeat length variation in the human ribosomal protein L14 gene
      (RPL14): localization to 3p21.3 and loss of heterozygosity in lung and oral
      cancers.
AB  - Chromosome 3p is consistently deleted in lung cancer, oral squamous cell
      carcinoma, and renal cell carcinoma, and is believed to contain several tumor
      suppressor genes. We have shown a role for chromosome 3 in tumor suppression by
      microcell-mediated chromosome transfer experiments. We have isolated a gene that
      is located at 3p21.3 within the smallest region of deletion overlap in lung
      tumors and is the human homolog of the ribosomal protein L14 gene (RPL14). The
      RPL14 sequence contains a highly polymorphic trinucleotide repeat array which
      encodes a variable-length polyalanine tract. Genotype analysis of RPL14 shows
      that this locus is 68% heterozygous in the normal population, compared with 25%
      in non-small cell lung cancer (NSCLC) cell lines (p = 0.008). Cell cultures
      derived from normal bronchial epithelium show a 65% level of heterozygosity,
      reflecting that of the normal population. Squamous cell carcinoma of the head and
      neck (SCCHN), which has the same risk factors as lung cancer and is hypothesized
      to have a similar etiology, demonstrates 54% loss of heterozygosity at the RNA
      level, suggesting that transcriptional loss may be a primary mechanism of RPL14
      alteration in SCCHN. In addition, RPL14 shows significant differences in allele
      frequency distribution in ethnically-defined populations, making this sequence a
      useful marker for the study of ethnicity-adjusted lung cancer risk.

PMID- 9920052
TI  - Application of random amplified polymorphic DNA PCR for genomic analysis of HIV-1
      infected individuals.
AB  - Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) is a DNA
      fingerprinting technique used to detect genomic polymorphisms. We employed
      sixteen different RAPD-PCR 10-mer primers to amplify DNA from the peripheral
      blood mononuclear cells (PBMC) of 80 HIV-1-infected individuals. These
      individuals were previously identified as either heterozygotes (+ /delta32) and
      homozygotes (+/+) for the CCR5 locus by PCR with gene specific primers. Four of
      the sixteen randomly selected RAPD primers produced distinguishable banding
      profiles between CCR5 (+/delta32) heterozygotes and CCR5 (+/+ ) homozygotes.
      Direct sequencing of some RAPD-PCR products obtained with one of the four RAPD
      primers that were tested yielded clearly readable, but limited sequences, which
      were similar to portions of the previously published sequences for (+/+ )
      homozygotes (98% similarity) and (+/delta32) heterozygotes (87% similarity) of
      the CCR5 alleles. Thus, the RAPD-PCR technique may be useful for the
      identification of human molecular markers that may correlate with susceptibility
      to HIV-1-infection, or differences in disease progression among HIV-l-infected
      individuals.

PMID- 9920053
TI  - Rapid characterization of mutations in amplified human hprt cDNA by
      polyacrylamide gel electrophoresis.
AB  - Compiling hprt mutation spectra involves the isolation and analysis of numerous 6
      thioguanine-resistant clones for identifying characteristic point mutations.
      Since cDNA amplificates are compulsory intermediates in most mutant
      classification protocols, we suggest their preliminary characterization by
      polyacrylamide gel electrophoresis for the rapid distinction of clonal and
      independent mutants and for streamlining mutant analysis procedures. Based on the
      human hprt cDNA sequence a strategy was developed for mapping missing exons by
      analytical digests with a small panel of restriction enzymes. In mutant
      classification schemes, polyacrylamide gel electrophoresis of AluI-digested cDNA
      amplificates increased the sensitivity for detecting RT-PCR products of reduced
      size, e.g., in the case of missing exon 5. Restriction analysis of cDNA
      amplificates from 109 independent mutant clones showed a significant increase of
      exon loss after NNK induction as compared to spontaneous or BaP-induced mutants.
      The determination of exon loss from cDNA amplificates, as carried out for 39
      independent mutant PCR products, might direct towards the genomic target
      sequences carrying the point mutations, that caused the aberrant splicing, thus
      eliminating the need of laborious multiplex PCR comprising all exons. For single
      strand conformation polymorphism (SSCP) analysis of five known point mutations,
      sub-amplificates comprising exons 7 and 8 of hprt cDNA were obtained. After a
      combined heat and alkali denaturation of the double-stranded PCR products, the
      samples were separated in pre-cast polyacrylamide gels under non-denaturing
      conditions. Five known nucleotide substitutions within the amplified region,
      including the C508T hot spot mutation, resulted in mobility shifts of single
      strand bands relative to the wild type pattern.

PMID- 9920054
TI  - Therapeutic controversy: Obesity--a modern-day epidemic.
AB  - While the hyperleptinemia of obesity is likely to be associated with the
      metabolic complications of obesity/hyperinsulinemia/insulin resistance, it is not
      associated with diabetes, with the relative hypercortisolism of upper body
      obesity, with hypertension in women, (it is in men), or with dyslipidemia.
      Overall, the correlations between leptin and the metabolic diseases associated
      with obesity are weak. The equivocal results of an association of leptin with
      components of the metabolic syndrome make it unlikely that leptin affects these
      directly. (On the other hand, these correlations, when found, preclude any causal
      relationship between leptin and metabolic diseases.) There are experimental data
      showing a definite role for insulin and glucocorticoids in the regulation of
      leptin, and of leptin in the regulation of insulin. More data are required on the
      effects of leptin, but it is likely that leptin will not be a major link between
      obesity and the metabolic syndrome. Certainly, however, when leptin is available
      for clinical use, its effect on different aspects of the metabolic syndrome will
      be worth studying.

PMID- 9920055
TI  - Clinical case seminar: Anti-thyroid drugs and antineutrophil cytoplasmic antibody
      positive vasculitis. A case report and review of the literature.

PMID- 9920056
TI  - Effects of 1-year treatment with octreotide on cardiac performance in patients
      with acromegaly.
AB  - The aim of the study was to investigate the effects of 1-yr treatment with
      octreotide (OCT) on left ventricular diastolic and systolic function, assessed at
      rest and during physical exercise by gated blood pool cardiac scintigraphy, in 30
      patients with active acromegaly. OCT was initially given at a dose of 0.05-0.1
      mg, 3 times daily, and the dose was subsequently increased to achieve GH/insulin
      like growth factor I (IGF-I) normalization. Hormone normalization after treatment
      was considered when basal and/or oral glucose test-suppressed GH values were
      below 2.5 and 1 microg/L, respectively, and IGF-I values were within the normal
      range for age. To evaluate the response to OCT treatment in terms of cardiac
      performance, the 30 patients were divided into 2 groups on the basis of
      normalized (in 13 patients) or nonnormalized (in 17 patients) circulating GH and
      IGF-I levels. At study entry, hypertension was found in 6 patients (20%),
      abnormal left ventricular diastolic filling was found in 12 patients (40%), and
      impaired left ventricular ejection fraction was found in 2 patients at rest
      (6.6%) and in 18 patients at peak exercise (60%). Before OCT treatment, exercise
      duration ranged from 6-10 min, and exercise workload ranged from 50-125 watts.
      After 1-yr treatment with OCT, a significant decrease in circulating GH and IGF-I
      levels was achieved in all patients, but normalization was obtained only in 13 of
      30 patients. In patients achieving circulating GH and IGF-I normalization after
      OCT treatment but not in those with persistently elevated hormone levels, a
      significant decrease in heart rate, both at rest (from 75.7 +/- 3.3 to 66.5 +/-
      2.9 beats/min; P < 0.01) and after exercise (from 137.5 +/- 4.9 to 123.7 +/- 4.1
      beats/min; P < 0.01), and a significant increase in left ventricular ejection
      fraction, both at rest (from 56.5 +/- 1.8% to 66.5 +/- 2.2%; P < 0.01) and after
      exercise (from 52.6 +/- 2.4% to 67.1 +/- 1.7%; P < 0.01), were found. In the 17
      patients who had persistently high circulating GH and IGF-I levels after 1 yr of
      OCT treatment, left ventricular ejection fraction was unchanged at rest but was
      significantly reduced after exercise compared to the basal value (from 64.9 +/-
      2.4% to 57.2 +/- 2.6%, P < 0.01); systolic blood pressure at rest was
      significantly increased (from 128.5 +/- 4.9 to 141.2 +/- 5.4 mm Hg; P < 0.05). In
      these 17 patients, the ejection fraction response to exercise was significantly
      impaired, mostly in those less than 40 yr of age (from 11.6 +/- 3.2% to -0.3 +/-
      5.6%; P < 0.05). In particular, among 9 patients who had a normal response to
      exercise at study entry, 6 developed an abnormal response after 1 yr. Left
      ventricular diastolic filling was unchanged by OCT treatment in all patients.
      Exercise duration (only in young patients from 7.5 +/- 0.5 to 9.3 +/- 0.7 min; P
      < 0.05) and exercise workload (in all 13 patients from 80.8 +/- 6.4 to 92.3 +/-
      5.9 watts; P < 0.05) were significantly increased in the group of patients with
      normalized GH and IGF levels, but not in the remaining 17 (from 7.6 +/- 0.4 to
      7.5 +/- 0.4 min and from 89.9 +/- 5.5 to 84.4 +/- 4.5 watts, respectively). In
      conclusion, the results of the present study indicate that suppression of basal
      or glucose-suppressed GH levels below 2.5 or 1 microg/L, respectively, together
      with normalization of plasma IGF-I levels for 1 yr are followed by a significant
      improvement, but not complete normalization, of left ventricular ejection
      fraction either at rest or at peak exercise without significant changes in
      diastolic filling. By contrast, the persistence for 1 yr of elevated hormone
      levels caused a significant increase in systolic blood pressure and impaired
      cardiac performance. These data suggest that prolonged suppression of circulating
      GH and IGF-I levels could normalize cardiac performance and probably reverse the
      poor prognosis for cardiovascular disease in acromegaly.

PMID- 9920057
TI  - Indications and limits of ultrasound-guided cytology in the management of
      nonpalpable thyroid nodules.
AB  - Although ultrasound (US)-guided fine needle aspiration biopsy (FNAB) is widely
      prescribed in nonpalpable thyroid nodules, the goal of this study was to define
      precisely the indications and limits of US-FNAB in a series of 450 nonpalpable
      nodules. Among 94 surgically controlled cases, 20 (8 infracentimetric and 12
      centimetric or supracentimetric) carcinomas were diagnosed. The diagnosis of
      malignancy was successfully made by US-FNAB in 16 of 20 carcinomas, 3 were missed
      because of insufficient cytological material, and 1 was misdiagnosed. US-FNAB
      sensitivity and specificity were 94% and 63%, respectively. A logistic model
      indicated that nodule size (P < 0.6) was not associated with histological
      diagnosis, but that solid hypoechoic features were more likely to be malignant (P
      < 0.0003), with US sensitivity and specificity for malignancy of 80% and 70%,
      respectively. Logistic regression indicated that adequate cytological material
      significantly increased with nodule size (P < 0.0001). This result outlined the
      limits of US-FNAB in small nodules. Hence, indication of US-FNAB appears
      judicious in centimetric or supracentimetric nodules or in solid and hypoechoic
      ones. Such a management would allow the discovery of 15 of 20 carcinomas and
      would avoid 16% of unnecessary biopsies.

PMID- 9920058
TI  - Diurnal rhythms of luteinizing hormone, follicle-stimulating hormone, and
      testosterone secretion before the onset of male puberty.
AB  - To investigate hormonal change before the onset of male puberty, we measured LH
      and FSH in serum samples drawn every 20 min for 24 h and measured testosterone
      hourly for 24 h. Forty-six boys (32 prepubertal and 14 pubertal) of short
      stature, between 4.4-19.3 yr of age, participated in this study. LH and FSH were
      measured using a time-resolved immunofluorometric assay, and testosterone was
      measured using high sensitivity RIA capable of detecting a testosterone
      concentration of 0.01 ng/mL. Diurnal rhythms of LH, FSH, and testosterone were
      apparent in all subjects, including those aged 4-5 yr. Serum LH and FSH
      concentrations showed night-day variation in a pulsatile fashion. The serum
      testosterone concentration was elevated at early morning in all subjects. Mean 24
      h LH, FSH, and testosterone concentrations of prepubertal subjects who did not
      attain puberty for at least 3 yr were 0.10 U/L, 0.63 U/L, and 0.06 ng/mL,
      respectively, whereas those of prepubertal subjects who attained puberty within 1
      yr (0.54 U/L, 1.68 U/L, and 0.10 ng/mL, respectively) were significantly higher.
      Furthermore, mean 24-h LH, FSH, and testosterone concentrations increased with
      developing puberty. All of the 46 subjects showed positive cross-correlation
      between the LH and testosterone time series. The mean lag time from the LH to the
      testosterone time series in the prepubertal subjects who attained puberty within
      1 yr (4.7 +/- 2.4 h, mean +/- SD) was shorter than that in the prepubertal
      subjects who attained puberty after at least 3 yr (7.3 +/- 2.2 h). This lag time
      decreased with developing puberty, plateauing at 1.4 +/- 0.9 h at midpuberty.
      Thus, the diurnal rhythms of LH, FSH, and testosterone already exist at 4-5 yr of
      age; serum LH, FSH, and testosterone levels increase before the onset of puberty;
      and a time delay is observed between the LH and testosterone time series that
      decreases before the onset of puberty.

PMID- 9920059
TI  - Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29
      polycystic ovary syndrome and 10 control families.
AB  - The aim of this study was to obtain evidence for the genetic basis of polycystic
      ovaries (PCO) and premature male pattern baldness (PMPB) by screening first
      degree relatives of women affected by polycystic ovary syndrome (PCOS). Because
      of the high prevalence of PCO in the general population, we also studied first
      degree relatives of ten asymptomatic control volunteers of reproductive age. The
      probands were recruited prospectively from infertility and endocrine clinics,
      where they presented with various clinical symptoms of PCOS. Each had PCO, on
      transvaginal ultrasound scan. The families of 29 probands and 10 volunteers
      agreed to take part in the study. Clinical, ultrasound, and biochemical
      parameters were used to define PCO/PCOS. All female relatives had an ovarian
      ultrasound scan and hormone profile performed. History was used to assign status
      in postmenopausal women. All male relatives were assessed for early onset (<30 yr
      old) male pattern baldness, by photographs. All relatives were assigned affected
      (PCO/PMPB) or nonaffected status, and segregation analysis was performed. Of the
      relatives of 29 PCOS probands, 15 of 29 mothers (52%), 6 of 28 fathers (21%), 35
      of 53 sisters (66%), and 4 of 18 brothers (22%) were assigned affected status.
      First-degree female relatives of affected individuals had a 61% chance of being
      affected. Of the first-degree male relatives, 22% were affected. Of a total of 71
      siblings of PCOS probands, 39 were affected, giving a segregation ratio of 39/32
      (55%), which is consistent with autosomal dominant inheritance for PCO/PMPB. In
      the control families, 1 of 10 probands (10%), 1 of 10 mothers (10%), no fathers,
      2 of 13 sisters (15%), and 1 of 11 brothers (9%) were affected. Of a total of 24
      siblings, 3 were affected (13%), giving a segregation ratio (observed/expected)
      of 3/12, which was significantly different from autosomal dominant inheritance.
      The inheritance of PCO and PMPB is consistent with an autosomal dominant
      inheritance pattern in PCOS families, perhaps caused by the same gene. There was
      no such genetic influence in families of women without PCOS. Sisters of PCOS
      probands with polycystic ovarian morphology were more likely to have menstrual
      irregularity and had larger ovaries and higher serum androstenedione and
      dehydroepiandrosterone-sulfate levels than sisters without PCO. This suggests a
      spectrum of clinical phenotype in PCOS families. Men with PMPB had higher serum
      testosterone than those without. Collectively, these data are consistent with a
      role for genetic differences in androgen synthesis, metabolism, or action in the
      pathogenesis of PCOS.

PMID- 9920060
TI  - Reproductive axis after discontinuation of gonadotropin-releasing hormone analog
      treatment of girls with precocious puberty: long term follow-up comparing girls
      with hypothalamic hamartoma to those with idiopathic precocious puberty.
AB  - Although the GnRH agonist analogs have become an established treatment for
      precocious puberty, there have been few long term studies of reproductive
      function and general health after discontinuation of therapy. To this end, we
      compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume
      (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of
      neurological and psychiatric problems in 2 groups of girls: those with precocious
      puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic
      precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8
      microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr
      and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The
      endocrine findings were also compared to those in 14 normal perimenarcheal girls.
      There were no differences between the HH and IPP groups in age or bone age at the
      start of treatment, at the end of treatment, or during GnRH analog therapy. We
      found that whereas the peak LH level was higher in HH than in IPP girls before
      (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9
      +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of
      the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range
      by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH
      levels in both HH and IPP groups tended to be lower than normal, whereas the peak
      FSH levels were not different from normal, so that the overall posttherapy LH/FSH
      ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP,
      2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at
      the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to
      increase in both groups over time to become larger than that in normal girls by 4
      5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P
      < 0.05). Whereas the onset of spontaneous menses varied widely in both groups,
      once menses had started, the HH group had a higher incidence of oligomenorrhea.
      Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH
      patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular
      menses. Live births of normal infants were reported by 2 HH and 2 IPP patients,
      and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients.
      BMI was greater than normal in HH and IPP both before treatment and at all
      posttherapy time points and tended to be higher in the HH patients. Marked
      obesity (BMI, +2 to +5.2 SD score) was observed in 5 HH and 6 IPP patients, 1 of
      whom had a BMI of +2.5 SD score and developed acanthosis nigricans, insulin
      resistance, and hyperglycemia. Seizure disorders developed during GnRH analog
      therapy in 5 HH and 1 IPP patient, and 2 additional HH girls developed severe
      depression and emotional lability posttherapy. Although the mean anterior
      posterior dimension of the hamartoma was larger in the HH patients with seizure
      than in those who were seizure free (1.7 +/- 1.2 vs. 0.9 +/- 0.4 cm; P < 0.05),
      no change in hamartoma size was observed either during or after therapy, and no
      patient has reported the onset of a seizure disorder posttherapy. Other than a
      tendency toward a larger MOV, a higher incidence of oligomenorrhea, obesity, and
      frequency of neurological disorders, recovery of the reproductive axis after GnRH
      analog therapy was not markedly different in HH compared to IPP. Continued follow
      up of these patients may determine whether the decreased LH responses and
      increased BMI in both groups compared to those in normal girls remain clinically
      significant problems.

PMID- 9920061
TI  - Clinical and biochemical phenotype of familial anterior hypopituitarism from
      mutation of the PROP1 gene.
AB  - We have investigated the largest family with PROP1 deficiency reported to date.
      Eight patients, aged 17-40 yr, in two sibships with possibly related mothers but
      no parental consanguinity were 109-137 cm in height (-8.8 to [minus]5.9 SD score)
      and sexually immature. None had received hormonal therapy. Affected individuals
      had similarities to and significant differences from patients with insulin-like
      growth factor I (IGF-I) deficiency due to GH receptor deficiency (GHRD) and
      normal thyroid function and sexual maturation. The differences from patients with
      GHRD include normal hand and foot length in seven of eight, normal arm span with
      relatively long legs, and persistence of extremely low levels of IGF-I into
      adulthood; similarities include the degree of growth failure, frequent but not
      uniform increased body weight for height or body mass index, and the presence of
      limited elbow extensibility and blue scleras in six of eight. Three patients had
      markedly increased sella turcica area for height age and bone age, determined
      from lateral skull films. The degree of sellar enlargement is variable in these
      two sibships. Serum GH concentrations were 0.1 ng/mL or less after clonidine
      ingestion. Other results were: IGF-I, 3-11 ng/mL (normal, 114-492); IGF-II, 185
      299 ng/mL (normal, 358-854); IGF-binding protein-1 (IGFBP-1), 12-200 ng/mL
      (normal, 13-73); IGFBP-2, 60-384 ng/mL (normal, 55-480); and IGFBP-3, 400-600
      ng/mL (normal, 2000-4000). The very low IGF-I and normal IGFBP-1 and -2 levels
      differ from findings in adults with GHRD. The GH-binding protein concentration
      was 58-799 pmol/L, with two patients above the normal range of 66-306. LH and FSH
      levels were very low, with no sex differences between serum levels of estradiol
      (3-6 pg/mL) and testosterone (3-10 ng/dL). PRL levels all were below normal.
      Serum concentrations of cortisol were normal. Serum T4 levels were uniformly low
      (<0.2-0.5; normal, 0.8-2.7 ng/dL), free T3 values were less than normal in seven
      of eight subjects, and total T3 concentrations were below normal in five of
      eight, but TSH levels were normal (0.58-2.18; normal, 0.4-4.2 mU/L). DNA
      specimens from affected individuals in each sibship were homozygous for a 2-bp
      deletion in exon 2 of the PROPI (Prophet of Pit-I) gene, which causes a shift of
      reading frames and results in a translational stop signal at codon 109. The
      mutant protein, when expressed in vivo lacks DNA-binding and transcriptional
      activation functions. The consequences of the PROPI abnormality in this and other
      kindreds include gonadotropin deficiency as well as the expected deficiencies in
      products of Pit-I-dependent somatotrophs, lactotrophs, and thyrotrophs. The
      severity of the hormone deficiency phenotype is compatible with the complete loss
      of PROP1 activity.

PMID- 9920062
TI  - Alterations of monocyte function in patients with growth hormone (GH) deficiency:
      effect of substitutive GH therapy.
AB  - GH deficiency (GHD) is associated with increased prevalence of atherosclerosis
      and cardiovascular morbidity. Because monocytes play a crucial role in the
      development of atherosclerosis, we investigated in the present study the effect
      of GH deficiency and subsequent GH replacement on monocytic function in
      hypopituitary subjects. Twelve patients were randomized to receive GH replacement
      therapy (either 3 or 6 microg/kg x day, s.c.) for 3 months. Plasma levels and
      monocyte production of cytokines and monocyte adhesion to endothelium were
      determined in controls and patients with GHD before and after GH treatment.
      Before GH therapy, patients with GHD had increased basal plasma tumor necrosis
      factor-alpha (TNF alpha; 220% over control values; P = 0.004) and interleukin-6
      (IL-6; 340% over control values; P 0.0009) levels. Basal monocyte production of
      both cytokines was also significantly higher in patients with GHD [484% over
      control values for TNF alpha (P = 0.0007); 1479% over control values for IL-6 (P
      = 0.035)]. GH treatment for 3 months led to a reduction in plasma TNF alpha (135%
      over control values; P = 0.03, pre- vs. post-GH therapy), monocyte TNF alpha
      production (204% over control values; P = 0.01), plasma IL-6 (219% over control
      values; P = 0.07), and monocyte IL-6 production (448% over control values; P =
      0.01). Plasma TNF alpha levels positively correlated with monocyte TNF alpha
      production in patients with GHD both before and after GH therapy (P = 0.003 and P
      = 0.049, respectively). A positive correlation (P = 0.0003) was also observed
      between monocyte TNF alpha production and monocyte IL-6 production. There were no
      correlations between these plasma cytokine levels or monocyte cytokine production
      and parameters of body composition, lipid profile, or IGF-I and IGF-binding
      protein-3 levels. Before GH treatment, adhesiveness of monocytes to cultured
      aortic endothelial cells was also enhanced. This alteration was not reversed by
      GH administration. In conclusion, our results demonstrate that markers of
      monocyte activation are increased in patients with GHD and that GH replacement
      partly reduces these abnormalities. Reduction of cellular activation of monocytes
      by GH therapy could potentially contribute to reduce the risk of cardiovascular
      events in patients with GHD.

PMID- 9920063
TI  - Adrenocorticotropin responses to naloxone in sons of alcohol-dependent men.
AB  - The endogenous opioid system is part of a neural circuitry functionally related
      to alcohol-seeking behaviors. A family history of alcoholism is the strongest
      predictor of future development of alcohol dependence. This study was designed to
      evaluate ACTH responses to opioid receptor blockade as a function of family
      history for alcohol dependence. The nonselective opioid antagonist naloxone
      stimulates ACTH secretion by blocking opioidergic input on paraventricular
      corticotropin-releasing factor neurons, thereby providing a methodology for
      comparing hypothalamic opioid tone between study groups. Sixty nonalcoholic
      subjects, aged 18-25 yr, were enrolled in a protocol to measure the ACTH response
      to naloxone. Thirty-two subjects were offspring from families with a high density
      of alcohol dependence and were designated as family history-positive subjects.
      Twenty-eight subjects were offspring of nonalcohol-dependent parents and were
      designated family history-negative subjects. Subjects received naloxone (125
      microg/kg) or placebo (0.9% saline) in double blind, randomized order. Plasma
      ACTH was monitored. Family history-positive men had increased ACTH response to
      naloxone compared to 1) family history-positive women, 2) family history-negative
      men, and 3) family history-negative women. Despite differences in plasma ACTH
      levels after naloxone administration, plasma naloxone concentrations did not
      differ between study groups. This finding suggests that nonalcoholic male
      offspring of alcohol-dependent men have altered endogenous opioid activity
      directed at hypothalamic corticotropin-releasing factor neurons.

PMID- 9920064
TI  - Screening for multiple endocrine neoplasia type 1 and hormonal production in
      apparently sporadic neuroendocrine tumors.
AB  - Screening was performed in 130 consecutive patients with apparently sporadic
      neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine
      neoplasia type 1 (MEN1) and hormonal production. Screening for MEN1 included
      measurement of serum calcium and PTH [PTH-(1-84)], gastrin, PRL, and insulin-like
      growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in
      patients with two components of the MEN1 syndrome. Screening for hormonal
      production included measurement of serum neuron-specific enolase (NSE),
      calcitonin (CT), glycoprotein alpha-subunit (GP alpha), hCG beta-subunit (free
      hCG beta), and somatostatin levels. Twenty-four-hour urinary free cortisol (UFC)
      and 5-hydroxyindolacetic acid (5-HIAA) determinations were also performed. Four
      patients had hyperparathyroidism, none of whom had pituitary or familial disease.
      Hyperprolactinemia was compatible with a pituitary disease in one patient. No
      acromegalic feature or any increase in IGF-I was found. Hypergastrinemia,
      compatible with an associated pancreatic NET, was found in one patient. Genetic
      screening of the MEN1 gene was performed in five of the six patients with two
      components of the MEN1 syndrome. A nonsense mutation (Arg108stop) was identified
      in the tumor of one patient. Elevated NSE, 5-HIAA, CT, GP alpha, free hCG beta,
      SMS, and nonsuppressible UFC were found in 47%, 46%, 14%, 19%, 12%, 3%, and 6% of
      NET patients, respectively. Production of CT, GP alpha, and free hCG beta was
      highly related to the primary site: all but two of these secretions originated in
      foregut NET. 5-HIAA secretion was found in 27% of foregut-derived and 85% of
      midgut-derived NET. In conclusion, MEN1 is a rare event in patients presenting
      with apparently sporadic NET. It occurred mainly in foregut NET and should be
      screened for by serum calcium and PTH-(1-84) measurements. Routine hormonal
      measurements should depend on the primary site. NSE, 5-HIAA, CT, and alphaGP
      should be routinely measured in foregut-derived NET; only serum NSE and 5-HIAA
      measurements are recommended in midgut-derived NET.

PMID- 9920065
TI  - Response of the pituitary-adrenal axis to hypoglycemic stress in women with the
      polycystic ovary syndrome.
AB  - The role of the adrenals in the polycystic ovary syndrome (PCOS) is debated. Both
      single steroid-converting enzyme abnormalities and increased adrenal activity
      have received support. The conventional Synacthen test using pharmacological
      doses of ACTH results in unphysiological levels of ACTH. Therefore, we used
      insulin-induced hypoglycemia (0.15 IU/kg BW) to asses the responses of ACTH,
      cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone,
      progesterone, 17-hydroxyprogesterone, and androstenedione in 18 women with PCOS
      and in 17 normal women of similar age and body mass index. The blood glucose
      concentration at 30 min was 2 mmol/L or less in all women, i.e. well below the
      threshold of the hormonal counterregulatory response. The women with PCOS showed
      a lower ACTH response, expressed as the maximum increment above basal [mean (95%
      confidence interval): PCOS, 11.1 (6.9-15.3); controls, 19.9 (13.8-26) pmol/L; P <
      0.05], but a quantitatively comparable [PCOS, 207.2 (148.5-266.5); controls,
      167.1 (100.6-233.2) nmol/L; P = NS] and more prompt cortisol response than the
      controls (by chi2 test, P < 0.05), resulting in a higher molar ratio between the
      maximum increments of cortisol and ACTH [PCOS, 13.9 (8.7-19); controls, 8.8 (5.7
      12); P < 0.05]. The women with PCOS did, however, show a more rapid decline in
      cortisol levels than the controls (P < 0.05 at 120 and 180 min). The responses of
      the androgens and intermediate adrenal steroids were similar in women with PCOS
      and controls. The findings suggest an adaptation to increased adrenal reactivity
      to endogenous ACTH in women with PCOS. Exposure to hypoglycemia as a model of
      stress was not followed by hypersecretion of adrenal androgens and revealed no
      signs of steroid enzyme disturbances in women with PCOS.

PMID- 9920066
TI  - Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding
      protein-3 concentrations in normal children and children with growth hormone
      deficiency.
AB  - To evaluate the role of serum free or unbound insulin-like growth factor I (IGF
      I) on bone growth, we measured serum free IGF-I levels in 354 healthy children
      and adults (193 males and 161 females, aged 0-40 yr) and in 21 prepubertal GH
      deficient (GHD) children (complete GHD, n = 5; partial GHD, n = 16) using a
      recently developed immunoradiometric assay. We obtained the following results. 1)
      In the normal children, the serum free IGF-I levels were low in infancy (<1 yr of
      age; males, 0.71 +/- 0.26 microg/L, mean +/- SD; females, 1.05 +/- 0.49
      microg/L), increased during puberty (males, 5.84 +/- 2.18 microg/L; females, 5.80
      +/- 1.49 microg/L), and declined thereafter. 2) Free IGF-I in the serum occupied
      about 0.95-2.02% of the total IGF-I values, with the highest ratio occurring in
      infancy (males, 1.77 +/- 0.60%; females, 2.02 +/- 0.87%). 3) The SD scores of
      serum free IGF-I in the 21 GHD children ranged from -3.30 to 0.30, and the 5
      complete GHD children had free IGF-I values more than -2 SD below those of age
      matched normal subjects. 4) There was a significant correlation between the SD
      scores of free IGF-I and those of total IGF-I (r = 0.715; P < 0.0005) in the GHD
      children. 5) In the 16 partial GHD children receiving GH treatment, the serum
      free IGF-I levels were elevated to 209% of pretreatment levels after 1 month of
      GH treatment and remained high during GH therapy. The GH-induced increase in the
      serum free IGF-I levels was significantly higher than those of the total IGF-I
      and IGF binding protein-3 levels. 6) The percent increase in the serum free IGF-I
      level after 1 month of GH treatment showed a significant positive correlation
      with that of the GH-induced improvement in the percent increase in the height
      velocity during 1 yr of GH therapy (r = 0.526; P < 0.05). These results show that
      free IGF-I in the serum has an essential role in bone formation because the
      higher free IGF-I levels were observed when the growth rate accelerated. The
      measurement of serum free IGF-I may become a useful tool for both diagnosing GH
      deficiency and predicting growth responses to long term GH therapy.

PMID- 9920067
TI  - Second generation assay for thyrotropin receptor antibodies has superior
      diagnostic sensitivity for Graves' disease.
AB  - Detection of autoantibodies to the TSH receptor (TSH-R) in Graves' disease has
      found widespread use in clinical routine and is performed mostly by commercial
      RRAs measuring TSH binding inhibitory activity. We report in this study on a
      second generation TSH binding inhibitory assay using the human recombinant TSH-R
      with two major improvements: 1) superior diagnostic sensitivity for Graves'
      disease, and 2) for the first time, nonradioactive and radioactive coated tube
      (CT) technology. Full-length human recombinant TSH-R was expressed in the K562
      leukemia cell line and grown in suspension at a high density. A murine monoclonal
      antibody was selected for binding to the native TSH-R without interfering with
      autoantibodies or TSH and was coated to polystyrene tubes. After detergent
      extraction, TSH-R was affinity immobilized on antibody-coated tubes. The binding
      of TSH to the TSH-R could be demonstrated by the addition of 125I- or acridinium
      ester-labeled bovine TSH, and this binding could be inhibited by sera from
      patients with Graves' disease up to 95%. Subsequently, these novel assays, a CT
      RRA and a CT luminescence receptor assay, were compared to the conventional RRA
      based on porcine antigen in a blinded clinical multicenter trial. Sera from 328
      patients with Graves' disease (86 untreated, 116 treated, and 126 in remission)
      and 520 controls (comprised of healthy blood donors and patients with autoimmune
      diseases or goiter) were tested in all 3 assays. Receiver-operating
      characteristic plot analysis resulted in a specificity of 99.6% with a
      sensitivity of 98.8% for both CT assays, compared to 99.6% specificity and 80.2%
      sensitivity for the conventional RRA (P < 0.001). In all 3 groups of patients
      with Graves' disease, the 2 CT assays were significantly more sensitive for the
      disease than the conventional assay, without loss of specificity in the control
      groups. This increase in sensitivity and the nonradioactive or radioactive CT
      format constitute a significant improvement over the currently available assays.

PMID- 9920068
TI  - Serum levels of 20-kilodalton human growth hormone (GH) are parallel those of 22
      kilodalton human GH in normal and short children.
AB  - Twenty-kilodalton human GH (20K), which is one of the human GH (hGH) variants, is
      thought to be produced by alternative premessenger ribonucleic acid splicing.
      However, its physiological role is still unclear due to the lack of a specific
      assay. We have measured serum 20K and 22-kDa hGH (22K) by specific ELISAs to
      investigate the physiological role of 20K in children. The subjects were 162
      normal children, aged 1 month to 20 yr; 12 patients with GH deficiency (GHD),
      aged 11 months to 13 yr; 57 children with non-GHD short stature, aged 2-17 yr;
      and 13 girls with Turner's syndrome, aged 5 months to 15 yr. Samples were
      collected at random from normal children and were collected after hGH provocative
      tests and 3-h nocturnal sleep from GHD, non-GHD short stature, and Turner's
      syndrome children. The mean basal serum concentrations of 22K and 20K were 2.4 +/
      2.8 ng/mL and 152.3 +/- 184.0 pg/mL in normal boys and 2.5 +/- 3.1 ng/mL and
      130.6 +/- 171.5 pg/mL in normal girls, respectively. The percentages of 20K
      (%20K) were 5.8 +/- 2.1% and 6.0 +/- 3.2% in 83 normal boys and 79 normal girls,
      respectively. There was no significant difference in %20K either among ages or
      between the prepubertal stage and the pubertal stage in normal boys and girls.
      The mean %20K values in basal samples of provocative tests in 12 patients with
      GHD, non-GHD short stature, and Turner's syndrome were 6.5 +/- 2.4%, 6.5 +/-
      3.8%, and 5.9 +/- 3.2%, respectively. There was no significant difference in %20K
      among normal children and these growth disorders, and there was no significant
      difference in %20K throughout the hGH provocative tests and 3-h nocturnal sleep
      in these growth disorders. There was also no significant correlation between the
      percentage of 20K and the height SD score or body mass index in either normal
      children or subjects with these growth disorders. In conclusion, the %20K is
      constant, regardless of age, sex, puberty, height SD score, body mass index, and
      GH secretion status. The regulation of serum 20K levels remains to be
      established.

PMID- 9920069
TI  - Female reproductive aging is marked by decreased secretion of dimeric inhibin.
AB  - The increase in serum FSH that accompanies female reproductive aging occurs
      before changes in estradiol (E2). A decrease in negative feedback from inhibin A
      (a product of the dominant follicle and corpus luteum) and/or inhibin B (secreted
      by developing follicles) may explain the rise in FSH with age. To test the
      hypothesis that decreases in inhibin A or inhibin B occur at an age at which the
      first increase in follicular phase FSH is evident, daily blood samples were
      obtained across the menstrual cycle from younger (<35 yr; n = 23) and older (35
      46 yr; n = 21) cycling women. These cross-sectional studies were complemented by
      longitudinal data in 3 women studied at a 10-yr interval. In the early follicular
      phase, mean inhibin B was lower in older cycling women (88 +/- 7 vs. 112 +/- 10
      pg/mL; P < 0.05) and FSH was higher (13.0 +/- 0.5 vs. 11.2 +/- 0.7 IU/L in older
      vs. younger, respectively; P < 0.04). In the mid- and late follicular phases,
      inhibin B was also lower in the older women (117 +/- 9 vs. 146 +/- 10 and 85 +/-
      8 vs. 117 +/- 11 pg/mL; P < 0.04), whereas E2 was higher (105 +/- 14 vs. 68 +/- 5
      and 240 +/- 27 vs. 163 +/- 9 pg/mL; P < 0.02), and no differences in FSH were
      observed in the two groups at these times. In women studied longitudinally, FSH
      and inhibin B varied inversely in the follicular phase. In the early luteal
      phase, mean inhibin B was lower in the older group (64 +/- 6 vs. 94 +/- 12 pg/mL;
      P < 0.03), and FSH was higher (12.5 +/- 1.0 vs. 9.7 +/- 0.6 IU/L; P < 0.03). In
      the mid- and late luteal phases, inhibin B was also lower in older subjects (21
      +/- 2 vs. 33 +/- 5 and 22 +/- 2 vs. 36 +/- 6 pg/mL; P < 0.02). No difference in
      inhibin A, E2, or progesterone was observed across the luteal phase, between the
      two groups. However, in all subjects studied longitudinally, increased age was
      associated with a decrease in inhibin A, inhibin B, and progesterone in the
      absence of changes in E2. Our conclusions were: 1) reproductive aging is
      accompanied by decreases in both inhibin B and inhibin A; 2) the decrease in
      inhibin B precedes the decrease in inhibin A and occurs in concert with an
      increase in E2, suggesting that inhibin B negative feedback is the most important
      factor controlling the earliest increase in FSH with aging; 3) these studies
      suggest that the decrease in inhibin B is the earliest marker of the decline in
      follicle number across reproductive aging.

PMID- 9920070
TI  - Oral progestogen combined with testosterone as a potential male contraceptive:
      additive effects between desogestrel and testosterone enanthate in suppression of
      spermatogenesis, pituitary-testicular axis, and lipid metabolism.
AB  - The effects of a synthetic oral progestogen, desogestrel (DSG), administered with
      low dose testosterone (T) were investigated to determine the optimal combination
      for suppression of gonadotropins and spermatogenesis to targets compatible with
      effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9
      yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG
      orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T
      enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To
      investigate the individual contribution to the combined action, DSG was
      administered alone for the first 3 weeks, and T enanthate was added on day 22.
      After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became
      azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less
      than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG
      with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and
      the suppression of sperm density was significantly greater than that in the 300
      microg DSG/100 mg T enanthate group, but was not different from that in the 150
      microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the
      first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively,
      of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T
      to the physiological range and induced a further fall in LH and FSH to the limits
      of assay detection. There was no consistent difference in mean LH and FSH levels
      among the three groups during treatment or recovery, except that FSH remained
      detectable in a higher proportion of samples from the group receiving 300 microg
      DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein
      cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%,
      10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone
      with no difference between 300 and 150 microg. Addition of T enanthate (both 50
      and 100 mg weekly) induced a further fall only in high density lipoprotein
      cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the combined actions
      of oral DSG with low doses of T enanthate were highly effective in suppressing
      pituitary-testicular functions in adult men. The optimal regimen for inducing
      azoospermia was 300 microg DSG daily with 50 mg T enanthate weekly. Oral DSG
      exerted discernible effects on lipid metabolism. We conclude that the combination
      of oral progestogens with low dose T is a promising approach to achieve effective
      reversible male contraception.

PMID- 9920071
TI  - Increased cortical bone content of insulin-like growth factors in acromegalic
      patients.
AB  - To investigate cortical bone composition and the role of the insulin-like growth
      factor (IGF) system in active acromegaly, iliac crest bone biopsies were obtained
      from 15 patients (3 women and 12 men), aged 21-64 yr (mean, 45.6 yr), and 25 age-
      and sex-matched controls (8 women and 17 men), aged 22-66 yr (mean, 44.6 yr).
      Levels of IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), IGFBP-5, and total
      protein were determined in extracts obtained after ethylenediamine tetraacetate
      and guanidine hydrochloride extraction. Osteocalcin and calcium were determined
      in extracts after HCl hydrolysis. Cortical bone contents of IGF-I, IGF-II, and
      IGFBP-5 were significantly elevated in the acromegalic patients compared with
      control values [91% (P < 0.001), 44% (P < 0.04), and 115% (P < 0.004),
      respectively]. There was no significant difference in IGFBP-3, osteocalcin,
      protein, and calcium between patients and controls. This study suggests that the
      increased levels of growth factors in cortical bone from acromegalics is a
      reflection of local production, secondary to a chronic systemic excess of GH and
      IGF-I.

PMID- 9920072
TI  - Lipid and lipoprotein concentrations in pregnancies complicated by intrauterine
      growth restriction.
AB  - Previous studies have shown that in preeclampsia, plasma lipids climb
      substantially above levels seen in normal pregnancies. Such lipid changes may
      play a role in the endothelial damage characteristic of preeclampsia. Pregnancies
      complicated by intrauterine growth restriction (IUGR), without preeclampsia, have
      similar placental pathology to preeclampsia despite the absence of the maternal
      systemic manifestations of hypertension and proteinuria. The aim of this study
      was to perform a cross-sectional study of lipid and lipoprotein concentrations in
      the third trimester, from normal pregnancies, and those complicated by IUGR
      without preeclampsia. Our hypothesis was that, in contrast to the exaggerated
      lipid changes seen in preeclampsia, lipid and lipoprotein concentrations in IUGR
      would be similar to those of matched healthy pregnant controls. Fasting blood
      samples for lipids and lipoprotein fractions were taken in the third trimester,
      from eight women with IUGR; and eight women with uncomplicated pregnancies,
      matched as a group for age, booking weight, parity, and gestational age at
      sampling. There were no significant differences (P > 0.05) in the median
      concentrations of triglyceride, high-density lipoprotein, and very-low-density
      lipoprotein 1 (VLDL1), between cases and controls. However, women with IUGR
      pregnancies had significantly lower cholesterol [4.95 mmol/L (3.35-7.10) vs. 7.47
      (5.75-8.45); median (range) for IUGR patients and controls, respectively; P <
      0.01], low-density lipoprotein (LDL)-cholesterol [2.45 mmol/L (0.95-3.60) vs.
      4.25 (3.35-5.60); P < 0.01], VLDL2 mass [59.0 mg/dL (37-87) vs. 103.0 (64-168); P
      < 0.01], intermediate-density lipoprotein mass [56.0 mg/dL (31-110) vs. 125.6 (91
      157); P < 0.01], and total LDL mass [221.0 mg/dL (104-237) vs. 380.3 (267-534); P
      < 0.01]. In addition, it was noteworthy that, with respect to LDL-cholesterol and
      total LDL mass, there was little or no overlap in the ranges of concentrations
      measured between cases and controls. Because VLDL2 and intermediate-density
      lipoprotein are the synthetic precursors to LDL in the circulation, their
      significantly lower median concentrations imply a failure of appropriate LDL
      synthesis in IUGR pregnancies. Whatever the mechanism, if our results are
      confirmed in larger studies and longitudinal investigations, then LDL-cholesterol
      measurements (when LDL-cholesterol fails to rise appropriately or is low in the
      third trimester) may be of use in identifying mothers with, or at risk of, a
      pregnancy complicated by IUGR.

PMID- 9920073
TI  - Growth hormone replacement therapy in the elderly with hypothalamic-pituitary
      disease: a dose-finding study.
AB  - Adults over the age of 60 yr with organic disease of the hypothalamic-pituitary
      axis have a 90% reduction in GH secretion. This is distinct from the
      hyposomatotropism associated with increasing age and results in a significant
      reduction in serum insulin-like growth factor I (IGF-I), an increase in fat mass,
      abnormal bone turnover, and an adverse lipid profile compared with those in
      healthy subjects of the same age. These findings suggest that the elderly with
      organic GH deficiency might benefit from GH replacement therapy. However, the
      dose of GH required to maintain serum IGF-I levels in the normal range while
      minimizing side-effects in this group of patients is unknown. We have studied 12
      patients with organic GH deficiency, aged 62.4-85.2 (median, 67.9 yr), each
      treated with three doses of GH (0.167, 0.33, and 0.5 mg/day). Each dose was
      administered for 12 weeks. The serum IGF-I level rose in a dose-related manner
      over the course of the study (P < 0.0001). From a baseline median (range) IGF-I
      concentration of 101 (49-148) microg/L to 149 (49-227) microg/L at 12 weeks (P =
      0.003 vs. baseline), 200 (70-453) microg/L at 24 weeks (P = 0.002 vs. baseline; P
      = 0.04 vs. 12 weeks), and 239 (122-502) microg/L at 36 weeks (P = 0.002 vs.
      baseline; P = 0.07 vs. 24 weeks). The age-specific IGF-I SD score exceeded normal
      in two subjects taking 0.33 mg/day and in six subjects taking 0.5 mg/day. Serum
      IGF-binding protein-3 also rose over the course of the study (P < 0.001);
      however, the greatest increase occurred during the first 12 weeks, after which
      the IGFBP-3 level plateaued. Body composition changed significantly during the
      study, with a fall in fat mass (P = 0.0003) and an increase in lean body mass (P
      = 0.0001). GH was well tolerated in this elderly group, all of whom completed the
      study. Three patients developed side-effects while taking 0.5 mg/day; two
      developed headaches, and one developed arthralgia. This study has demonstrated
      that the GH replacement dose in elderly subjects is considerably lower than that
      required by younger adults with GH deficiency. In 50% of the subjects a dose of
      0.5 mg/day was excessive, whereas 83% maintained their serum IGF-I within normal
      limits while taking 0.33 mg/day. No patient exhibited a supranormal IGF-I level
      on 0.17 mg/day.

PMID- 9920074
TI  - Body composition, visceral fat, leptin, and insulin resistance in Asian Indian
      men.
AB  - There is a high prevalence of type 2 diabetes mellitus and coronary artery
      disease among urban and migrant Asian Indians despite the absence of traditional
      risk factors. Evidence exists that Asian Indians are more hyperinsulinemic than
      Caucasians and that hyperinsulinemia may be important in the development of these
      diseases. To test whether insulin action was related to total or regional
      adiposity and to explore the potential role of plasma leptin and lipids, we
      measured insulin-mediated glucose disposal by the euglycemic insulin clamp,
      adipose distribution and muscle volume using computed axial tomography, and
      fasting serum leptin and lipid levels in 20 healthy Asian Indian male volunteers
      (age, 36 +/- 10 yr). A mean body mass index of 24.5 +/- 2.5 kg/m2 was associated
      with an unusually high percentage of body fat (33 +/- 7%). The majority of the
      fat was sc, and 16% was visceral (intraabdominal) adipose tissue. The majority
      (66%) of these nonobese men were insulin resistant. The mean fasting serum leptin
      level was 7.6 +/- 3.3 ng/mL. Insulin action was inversely correlated with
      visceral adipose tissue, not total or abdominal sc adipose tissue. In contrast,
      leptin levels correlated with sc and total (not visceral) adipose tissue. Serum
      triglyceride and high density lipoprotein cholesterol levels were inversely
      correlated with each other and were directly related to insulin resistance and
      visceral (not subcutaneous) fat. Increased visceral fat in Asian Indians is
      associated with increased generalized obesity, which is not apparent from their
      nonobese body mass index. Increased visceral fat is related to dyslipidemia and
      increased frequency of insulin resistance and may account for the increased
      prevalence of diabetes mellitus and cardiovascular disease in Asian Indians.

PMID- 9920075
TI  - Decreased bone formative and enhanced resorptive markers in human
      immunodeficiency virus infection: indication of normalization of the bone
      remodeling process during highly active antiretroviral therapy.
AB  - As cytokines and 1,25-dihydroxyvitamin D [1,25-(OH)2D] appear to have an
      important role in bone homeostasis, we examined the possibility that human
      immunodeficiency virus (HIV)-infected patients, characterized by enhanced levels
      of proinflammatory cytokines and 1,25-(OH)2D deficiency, have disturbed bone
      metabolism by analyzing serum markers of bone formation (osteocalcin) and bone
      resorption (C-telopeptide) in 73 HIV-infected patients. HIV-infected patients
      with advanced clinical and immunological disease and high viral load were
      characterized by increased C-telopeptide and particularly by markedly depressed
      osteocalcin levels. HIV-infected patients had enhanced activation of the TNF
      system. Serum concentrations of p55 and p75-TNF receptors were negatively
      correlated with osteocalcin, and p75-TNF receptor was positively correlated with
      C-telopeptide. HIV-infected patients with advanced disease also had decreased
      serum concentrations of 1,25-(OH)2D, but this parameter was not correlated with
      osteocalcin or C-telopeptide. During 24 months with highly active antiretroviral
      therapy there was a marked rise in serum osteolcalcin levels together with a
      profound fall in viral load and TNF components and a marked rise in CD4+ T cell
      counts. Also, there was a shift from no correlation to a significant correlation
      between osteocalcin and C-telopeptide levels during such therapy. The present
      study suggests disturbed bone formation and resorption during HIV infection. Our
      findings indicating synchronization of bone remodeling during highly active
      antiretroviral therapy may represent a previously unrecognized beneficial effect
      of such therapy and expand our knowledge of the interactions between cytokines
      and bone in the bone-remodeling process.

PMID- 9920076
TI  - Dangerous dogmas in medicine: the nonthyroidal illness syndrome.

PMID- 9920077
TI  - Prevalence and predictors of risk for type 2 diabetes mellitus and impaired
      glucose tolerance in polycystic ovary syndrome: a prospective, controlled study
      in 254 affected women.
AB  - Women with polycystic ovary syndrome (PCOS) are insulin resistant, have insulin
      secretory defects, and are at high risk for glucose intolerance. We performed
      this study to determine the prevalence of glucose intolerance and parameters
      associated with risk for this in PCOS women. Two-hundred and fifty-four PCOS
      women, aged 14-44 yr, were prospectively evaluated at 2 centers, 1 urban and
      ethnically diverse (n = 110) and 1 rural and ethnically homogeneous (n = 144).
      The rural PCOS women were compared to 80 control women of similar weight,
      ethnicity, and age. A 75-g oral glucose challenge was administered after a 3-day
      300-g carbohydrate diet and an overnight fast with 0 and 2 h blood samples for
      glucose levels. Diabetes was categorized according to WHO criteria. The
      prevalence of glucose intolerance was 31.1% impaired glucose intolerance (IGT)
      and 7.5% diabetes. In nonobese PCOS women (body mass index, <27 kg/m2), 10.3% IGT
      and 1.5% diabetes were found. The prevalence of glucose intolerance was
      significantly higher in PCOS vs. control women (chi2 = 7.0; P = 0.01; odds ratio
      = 2.76; 95% confidence interval = 1.23-6.57). Variables most associated with
      postchallenge glucose levels were fasting glucose levels (P < 0.0001), PCOS
      status (P = 0.002), waist/hip ratio (P = 0.01), and body mass index (P = 0.021).
      The American Diabetes Association criteria applied to fasting glucose
      significantly underdiagnosed diabetes compared to the WHO criteria (3.2% vs.
      7.5%; chi2 = 4.7; P = 0.046; odds ratio = 2.48; 95% confidence interval = 1.01
      6.69). We conclude that 1) PCOS women are at significantly increased risk for IGT
      and type 2 diabetes mellitus at all weights and at a young age; 2) these
      prevalence rates are similar in 2 different populations of PCOS women, suggesting
      that PCOS may be a more important risk factor than ethnicity or race for glucose
      intolerance in young women; and 3) the American Diabetes Association diabetes
      diagnostic criteria failed to detect a significant number of PCOS women with
      diabetes by postchallenge glucose values.

PMID- 9920078
TI  - Adipose tissue distribution pattern in patients with familial partial
      lipodystrophy (Dunnigan variety).
AB  - Familial partial lipodystrophy, Dunnigan type (FPLD), is a rare autosomal
      dominant genetic disorder characterized by gradual loss of sc fat from the
      extremities, commencing at the time of puberty. Excess fat deposition may occur
      in the face and neck area. Limited information is available about adipose tissue
      distribution in patients with FPLD. To investigate whether there is a unique
      pattern of fat distribution in both affected men and women with FPLD, we
      performed whole-body magnetic resonance imaging in one male and three female
      patients from two pedigrees. Magnetic resonance imaging studies confirmed the
      clinical findings of near-total absence of sc fat from all extremities. Reduction
      in sc adipose tissue from the truncal area was more prominent anteriorly than
      posteriorly. Increased fat stores were observed in the neck and face.
      Intermuscular adipose tissue in the extremities and pelvic area were subjectively
      increased. Intraabdominal and intrathoracic adipose tissue was not reduced. Bone
      marrow fat, as well as mechanical adipose tissue, was present in normal amounts.
      The pattern of fat distribution in the male and females was similar. We conclude
      that FPLD results in a characteristic absence of sc fat from the extremities,
      with preservation of intermuscular fat stores.

PMID- 9920079
TI  - Six-year results of spironolactone and testolactone treatment of familial male
      limited precocious puberty with addition of deslorelin after central puberty
      onset.
AB  - Short term treatment with spironolactone, testolactone, and, after the onset of
      central puberty, deslorelin can normalize the rate of growth and bone maturation
      in boys with familial male-limited precocious puberty. To test the hypothesis
      that this treatment can achieve long term normalization of the growth and
      development of these children, we examined the growth rate, bone maturation rate
      (change in bone age/change in chronological age), and predicted adult height of
      10 boys who were treated with spironolactone (5.7 mg/kg x day) and testolactone
      (40 mg/kg x day) for at least 6 yr. Deslorelin (4 microg/kg x day) treatment was
      initiated 2.6 +/- 1.3 yr after beginning spironolactone and testolactone
      treatment. The growth rate normalized within 1 yr of starting treatment and
      remained normal during the next 5 yr of treatment (P < 0.001). The rate of bone
      maturation normalized during the second year of treatment and remained normal
      thereafter (P < 0.001). Predicted height increased from 160.7 +/- 14.7
      centimeters at baseline to 173.6 +/- 10.1 centimeters after 6 yr of treatment (P
      < 0.05 during the fourth through the sixth year of treatment compared to
      baseline). We conclude that long term treatment with spironolactone,
      testolactone, and, after central puberty, deslorelin normalizes the growth rate
      and bone maturation and improves the predicted height in boys with familial male
      limited precocious puberty. The ultimate effect of this approach on adult height
      will require further study.

PMID- 9920080
TI  - Low dose estrogen and calcium have an additive effect on bone resorption in older
      women.
AB  - Previous studies have shown that treatment with estrogen or calcium decreases
      bone turnover in older women. The mechanisms by which estrogen and calcium exert
      their effects are probably different. We therefore examined the possibility of an
      additive or synergistic effect of combined treatment with calcium and low dose
      estrogen on bone turnover in older women, using biochemical markers. Thirty-one
      healthy women over 70 yr of age were randomized to 12 weeks of treatment with
      either micronized 17beta-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day
      elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the
      end of the initial 12-week treatment period, both groups received both Ca+D and
      E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks
      without any treatment and served as a control group. Serum and urine were
      collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after
      treatment was terminated for measurement of biochemical markers of bone turnover.
      Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I
      procollagen peptide; markers of bone resorption were urinary cross-linked C
      telopeptides and N-telopeptides of type I collagen, serum cross-linked N
      telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and
      serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in
      bone turnover measures over time by group. All markers of bone resorption
      decreased with initial treatment and decreased further with combination therapy
      (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not
      with E2 alone; there was no additional effect of combination therapy on formation
      markers compared to Ca+D alone. Neither markers of formation nor resorption
      changed in the control group. These results suggest that there is an additive
      effect of low dose estrogen and calcium on bone resorption, but not on bone
      formation, in older women. Thus, the combination of low dose estrogen plus
      calcium is likely to be more effective in older women than either treatment
      alone.

PMID- 9920081
TI  - Influence of obesity and body fat distribution on postprandial lipemia and
      triglyceride-rich lipoproteins in adult women.
AB  - We know that upper body obesity is associated with metabolic complications, but
      we don't know how regional body fat distribution influences postprandial lipemia
      in obese adults. Thus, this study explored the respective effects of android or
      gynoid types of obesity and fasting triglyceridemia on postprandial lipid
      metabolism and especially triglyceride-rich lipoproteins. Twenty-four obese and 6
      lean normotriglyceridemic women (control), age 24-57 yr, were enrolled. Among
      obese women with an android phenotype, 9 exhibited normal plasma triglyceride
      levels (mean: 1.38 mmol/L) (NTAO), and 7 displayed a frank hypertriglyceridemia
      (mean: 2.40 mmol/L) (HTAO). The 8 patients with a gynoid phenotype had normal
      triglyceride levels (mean: 1.00 mmol/L) (GO). All were given a mixed test meal
      providing 40 g triglycerides. Serum and incremental chylomicron triglycerides 0-7
      h areas under the curve (AUCs) as well as triglyceride levels in apoB-48
      containing triglyceride-rich lipoprotein (TRLs) or chylomicrons were
      significantly higher in HTAOs and NTAOs than in GOs and controls postprandially.
      The size of chylomicron particles was bigger in controls and GOs than in HTAOs
      and NTAOs postprandially. Android obese subjects showed abnormally elevated
      fasting apoB-48 and apoB-100 triglyceride-rich lipoprotein (TRL) levels. Most
      abnormalities that were found correlated to plasma levels of insulin and apoC
      III. In conclusion, an abnormal postprandial lipid pattern is a trait of
      abdominal obesity even without fasting hypertriglyceridemia.

PMID- 9920082
TI  - Soy isoflavones exert modest hormonal effects in premenopausal women.
AB  - Soy isoflavones are hypothesized to be responsible for changes in hormone action
      associated with reduced breast cancer risk. To test this hypothesis, we studied
      the effects of isoflavone consumption in 14 premenopausal women. Isoflavones were
      consumed in soy protein powders and provided relative to body weight (control
      diet, 10 +/- 1.1; low isoflavone diet, 64 +/- 9.2; high isoflavone diet, 128 +/-
      16 mg/day) for three menstrual cycles plus 9 days in a randomized cross-over
      design. During the last 6 weeks of each diet period, plasma was collected every
      other day for analysis of estrogens, progesterone, LH, and FSH. Diet effects were
      assessed during each of four distinctly defined menstrual cycle phases. Plasma
      from the early follicular phase was analyzed for androgens, cortisol, thyroid
      hormones, insulin, PRL, and sex hormone-binding globulin. The low isoflavone diet
      decreased LH (P = 0.009) and FSH (P = 0.04) levels during the periovulatory
      phase. The high isoflavone diet decreased free T3 (P = 0.02) and
      dehydroepiandrosterone sulfate (P = 0.02) levels during the early follicular
      phase and estrone levels during the midfollicular phase (P = 0.02). No other
      significant changes were observed in hormone concentrations or in the length of
      the menstrual cycle, follicular phase, or luteal phase. Endometrial biopsies
      performed in the luteal phase of cycle 3 of each diet period revealed no effect
      of isoflavone consumption on histological dating. These data suggest that effects
      on plasma hormones and the menstrual cycle are not likely to be the primary
      mechanisms by which isoflavones may prevent cancer in premenopausal women.

PMID- 9920083
TI  - The effect of lithium on calcium-induced changes in adrenocorticotrophin levels.
AB  - The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the
      parathyroid gland and other organs, including the brain. Chronic lithium (Li)
      therapy causes a significant alteration in Ca-sensing by the CaR-expressing
      parathyroid chief cells through an unknown mechanism, shifting the PTH set-point
      (the level of Ca that half-maximally suppresses PTH secretion) to the right. Ca
      is known to stimulate ACTH levels in normal subjects, and baseline ACTH levels
      are increased in patients with bipolar disorder. Because the stimulation of ACTH
      secretion by Ca likely involves the CaR, the aim of this study was to investigate
      the effects of Li on Ca-induced changes in ACTH levels, using Ca and citrate
      infusions in seven Li-treated patients and seven controls. During the Ca
      infusion, increments in serum-ionized Ca concentration (Ca(i)) were accompanied
      by increments in ACTH levels that were significantly greater in the Li-treated
      group, P = 0.014, by ANOVA. Also, cortisol levels increased significantly in the
      Li-treated, but not the control group, during the Ca infusion, P < 0.0001. There
      was a statistically significant shift in the midpoint of the Ca(i)/ACTH curve, to
      the right, in the Li-treated group, compared with the controls (P = 0.042), that
      was largely caused by an effect of Li on Ca(i). However, for comparable levels of
      Ca(i), there were no significant differences in the levels of ACTH between the
      two groups. Therefore, within the physiological range of Ca, there was no effect
      of Li on Ca(i)-induced change in ACTH levels.

PMID- 9920084
TI  - Quantitative assessment of cross-sectional muscle area, functional status, and
      muscle strength in men with the acquired immunodeficiency syndrome wasting
      syndrome.
AB  - The acquired immunodeficiency syndrome wasting syndrome (AWS) in men is
      characterized by the loss of lean body mass out of proportion to weight. Although
      the wasting syndrome has been thought to contribute to reduced functional
      capacity, the relationships among lean body mass, muscle size, functional status,
      and regional muscle strength have not previously been investigated in this
      population. In this study, 24 eugonadal men with the AWS (weight <90% of the
      ideal body weight or weight loss >10% from preillness maximum) underwent
      determination of body composition by dual energy x-ray absorptiometry (DXA), 40K
      isotope analysis, urinary creatinine excretion, and quantitative computed
      tomographic analysis of cross-sectional muscle areas of the midarm and thigh.
      Overall exercise functional capacity was evaluated using the 6-min walk test, and
      performance of upper and lower extremities was determined with the quantitative
      muscle function test. Subjects were 37 +/- 1 yr of age and weighed 95.5 +/- 3.0%
      of ideal body weight, with a body mass index of 21.9 +/- 0.7 kg/m2 and an average
      weight loss of 15 +/- 1%. The mean CD4 count among the subjects was 354 +/- 70
      cells/mm3, and viral load was 58,561 +/- 32,205 copies. Sixty-two percent of
      subjects were receiving protease inhibitor therapy. The subjects demonstrated 90%
      of the expected muscle mass by the creatinine height index method. Overall
      performance status on the Karnofsky scale was highly correlated to weight (r =
      0.51; P = 0.018; by body mass index), lean body mass (r = 0.46; P = 0.036; by
      DXA), and body cell mass (r = 0.47; P = 0.037; by 40K isotope analysis). Cross
      sectional muscle area of the upper extremity was the best predictor (P < 0.001)
      of Karnofsky score, accounting for 52% of the variability in a stepwise
      regression analysis. Upper body muscle strength was most significantly predicted
      by lean body mass (by DXA; r2 = 0.78; P < 0.0001), whereas lower body strength
      and performance on the 6-min walk test were best predicted by lower extremity
      cross-sectional muscle area (r2 = 0.70; P < 0.0001 and r2 = 0.26; P = 0.030,
      respectively). These data demonstrate that cross-sectional muscle area is highly
      predictive of functional status and muscle strength in men with the AWS.

PMID- 9920085
TI  - Testosterone administration preserves protein balance but not muscle strength
      during 28 days of bed rest.
AB  - Decrements in muscle strength as a result of prolonged bed rest are well defined,
      but little is known about potential countermeasures for preventing loss of
      strength under this condition. The purpose of this study was to determine whether
      testosterone administration would preserve protein balance and muscle strength
      during prolonged bed rest. Ten healthy men (age, 36 +/- 2 yr; height, 177.2 +/-
      3.4 cm; weight, 80.5 +/- 3.9 kg; mean +/- SE) were admitted to our in-patient
      metabolic unit. After a 1-week ambulatory run-in period, each subject was
      confined to bed for 28 days at 6 degree head-down tilt while receiving a daily
      oral dose of T3 (50 microg/day). During the bed rest/T3 period, six of the men
      were randomized to receive testosterone enanthate by i.m. injection (T; 200
      mg/week) while four received placebo in a double blind fashion. Nitrogen balance
      was determined throughout, and whole body [13C]leucine kinetics were assessed at
      baseline and on day 26 of bed rest. Before bed rest and on the third day of
      reambulation, the muscle strength of the knee extensors and flexors and shoulder
      extensors and flexors was determined at 60 degrees/s on a Cybex isokinetic
      dynamometer. Despite improved [13C]leucine kinetics and maintenance of nitrogen
      balance and lean body mass in T-treated subjects, little preservation of muscle
      strength, particularly in the knee extensors, was noted. Muscle strength
      [reported as the best work repetition in foot-pounds (FtLb)] for right knee
      extensors declined (P = 0.011) similarly in both groups; from 165 +/- 15 to 126
      +/- 18 FtLb in T-treated men and from 179 +/- 22 to 149 +/- 13 FtLb in placebo
      treated men. Overall, there was less of a decline in extension and flexion
      strength of the shoulder compared to the knee, with no benefit from T. These
      results suggest that in the absence of daily ambulatory activity, T
      administration will not increase or, in the case of this bed rest model, preserve
      muscle strength.

PMID- 9920087
TI  - MEN1 gene analysis in sporadic adrenocortical neoplasms.
AB  - Adrenocortical tumors occur as sporadic tumors, as part of the multiple endocrine
      neoplasia type 1 (MEN1) syndrome or as part of other hereditary disorders. We
      recently cloned the MEN1 gene, a tumor-suppressor gene located on chromosome
      11q13. Subsequently, we showed that sequential somatic inactivation of both
      alleles of the MEN1 gene contributes to the development of some sporadic
      endocrine neoplasms (parathyroid, enteropancreatic neuroendocrine, bronchial
      carcinoid, and pituitary tumors). We now studied whether somatic inactivation of
      the MEN1 gene contributes to the pathogenesis of sporadic adrenocortical
      neoplasms. Seven adrenocortical carcinomas, 2 adrenocortical carcinoma cell
      lines, and 11 aldosterone-secreting, 8 cortisol-secreting, and 5 nonsecreting
      benign adrenocortical tumors were studied. Seven tumors (5 of 5 carcinomas, 2 of
      21 nonsecreting benign adenomas; P < 0.001) exhibited loss of heterozygosity on
      11q13. All 33 tumors and cell lines were screened for mutation throughout the
      MEN1 open-reading frame and adjacent splice junctions. None exhibited a mutation
      within the MEN1-coding region. We conclude that somatic MEN1 mutation within the
      MEN1-coding region does not occur commonly in sporadic adrenocortical tumors,
      although the majority of adrenocortical carcinomas exhibit 11q13 loss of
      heterozygosity.

PMID- 9920086
TI  - Undetectable inhibin B serum levels in men after testicular irradiation.
AB  - A group of men treated with testicular irradiation for carcinoma in situ in the
      remaining testis after orchidectomy for unilateral testicular germ cell cancer
      was used as a model to study of the effect of selective eradication of germ cells
      on the levels of serum inhibin B in the human male. Thirteen men with verified
      spermatogenesis and detectable preirradiation levels of serum inhibin B (median,
      55; range, 23-193 pg/mL) were investigated before and after testicular
      irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12
      months (median, 5 months) after radiotherapy (<20 pg/mL). Correspondingly, serum
      FSH increased in all men after radiotherapy [from a median of 9.6 (range, 3.0-24)
      IU/L to a median of 28 (range, 15-70) IU/L); P < 0.001]. Histological
      investigation showed a Sertoli cell-only pattern in all patients after
      radiotherapy. Neither LH nor testosterone showed a significant decrease after
      radiotherapy. Our data indicate that inhibin B production sufficient to maintain
      detectable serum levels in adults requires spermatogenic activity.

PMID- 9920088
TI  - Synchronous fluctuations of blood insulin and lactate concentrations in humans.
AB  - Oscillatory organization is a universal mode of signal transduction in living
      organisms. In vitro studies suggest spontaneous pulsatile fluctuations of
      intracellular energy metabolism. It is possible that, in vivo, some of these
      processes are synchronized by the pulsatile release of insulin. We assessed a
      potential coupling among plasma insulin, glucose, and lactate concentrations, by
      frequent blood sampling for 24 h in 11 healthy volunteers. Insulin sensitivity
      was assessed using the euglycemic hyperinsulinemic clamp technique. Lactate
      concentrations exhibited pulsatile fluctuations at an average interval of 84 +/-
      11 min, whereas sodium and pH were nonpulsatile. The lactate concentration pulses
      closely corresponded to insulin oscillations, which occurred with a periodicity
      of 86 +/- 11 min. Blood glucose also fluctuated during daytime at an interval of
      89 +/- 32 min. During nighttime, the frequency and amplitude of glucose
      oscillations were lower. The daytime profiles showed significant temporal
      coupling and pattern synchrony among insulin, lactate, and glucose. Only the
      close temporal relationship between insulin and lactate release persisted during
      nighttime. The temporal coupling and pattern synchrony between insulin and
      lactate were correlated inversely with insulin sensitivity, and positively with
      the degree of abdominal obesity. Our results suggest that: 1) the concentration
      of lactate, an indicator of cellular energy metabolism, fluctuates periodically
      in vivo; 2) the lactate concentrations fluctuate in synchrony with insulin
      pulses; and 3) such coupling is more pronounced in obese, insulin-resistant
      individuals.

PMID- 9920089
TI  - Ovarian responses in women to recombinant follicle-stimulating hormone and
      luteinizing hormone (LH): a role for LH in the final stages of follicular
      maturation.
AB  - During the follicular phase of the menstrual cycle, FSH stimulates follicular
      growth, granulosa cell aromatase activity, induction of LH receptors on the
      granulosa cell membrane, and estradiol secretion. As a result of negative
      feedback of estradiol on the pituitary, serum FSH concentrations decline. Despite
      the fall in FSH concentrations, the maturing follicle continues to develop to the
      preovulatory stage. In a prospective randomized trial, we tested the hypothesis
      that a key mechanism by which the dominant follicle continues to develop in the
      face of decreasing concentration of FSH is by acquiring LH responsiveness. In 24
      women, pituitary gonadotropin secretion was down-regulated with a GnRH agonist.
      Follicular growth was then stimulated with recombinant human FSH (r-hFSH) until a
      14-mm follicle was identified by ultrasound. The women were then randomized to 1
      of 4 groups for a 2-day period: continued r-hFSH treatment, substitution of r
      hFSH with saline, low dose r-hLH (150 IU, twice daily), or high dose r-hLH (375
      IU, twice daily). Serum estradiol concentrations in the women receiving saline
      declined by the end of the 2-day randomization period. In contrast, serum
      estradiol concentrations continued to rise in women receiving either r-hFSH or r
      hLH compared with those in the saline-treated group (P < 0.05). Pregnancies
      occurred in each of the gonadotropin treatment groups. These findings indicate
      that once FSH initiates follicular growth, either FSH or LH is capable of
      sustaining follicular estradiol production. Extrapolating these findings to the
      normal menstrual cycle suggests that the maturing follicle may continue to
      develop in the presence of diminishing FSH concentrations by acquiring the
      capacity to respond to LH.

PMID- 9920090
TI  - High gastrin and cholecystokinin (CCK) gene expression in human neuronal, renal,
      and myogenic stem cell tumors: comparison with CCK-A and CCK-B receptor contents.
AB  - Gastrin and cholecystokinin (CCK) are two major regulatory peptides synthesized
      by human gut and brain tissues as well as by selected tumors, in particular
      gastrin-producing neuroendocrine tumors. In the present study we have evaluated
      gastrin and CCK gene expression in a group of primary human tumors, including
      neuronal, renal, and myogenic stem cell tumors, using in situ hybridization
      techniques. In addition, CCK-A and CCK-B receptors were evaluated in the same
      group of tumors with receptor autoradiography. Most tumors had gastrin messenger
      ribonucleic acid (mRNA): 10 of 11 medulloblastomas, 5 of 5 central primitive
      neuroectodermal tumors, 11 of 11 Ewing sarcomas, 8 of 10 neuroblastomas, 4 of 4
      Wilms' tumors, 5 of 5 rhabdomyosarcomas, and 10 of 10 leiomyosarcomas. CCK mRNA
      was restricted predominantly to Ewing sarcomas (9 of 11) and leiomyosarcomas (5
      of 10). CCK-A and CCK-B receptors were not frequently found in these tumors,
      except for leiomyosarcomas. These data suggest that gastrin and CCK may play a
      previously unrecognized role in this group of human stem cell tumors. If the
      increased gastrin mRNA indeed translates into increased gastrin production,
      measurement of gastrinemia may have a diagnostic significance in the early
      detection of these tumors. As these two hormones have been reported to act as
      potent growth factors, they may be of pathophysiological relevance for patients
      with such stem cell tumors.

PMID- 9920092
TI  - Loss of heterozygosity on chromosome 11q13 in two families with
      acromegaly/gigantism is independent of mutations of the multiple endocrine
      neoplasia type I gene.
AB  - Familial acromegaly/gigantism occurring in the absence of multiple endocrine
      neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families
      since the biochemical diagnosis of GH excess became available, and the genetic
      defect is unknown. In the present study we examined 2 unrelated families with
      isolated acromegaly/gigantism. In family A, 3 of 4 siblings were affected, with
      ages at diagnosis of 19, 21, and 23 yr. In family B, 5 of 13 siblings exhibited
      the phenotype and were diagnosed at 13, 15, 17, 17, and 24 yr of age. All 8
      affected patients had elevated basal GH levels associated with high insulin-like
      growth factor I levels and/or nonsuppressible serum GH levels during an oral
      glucose tolerance test. GHRH levels were normal in affected members of family A.
      An invasive macroadenoma was found in 6 subjects, and a microadenoma was found in
      1 subject from family B. The sequence of the GHRH receptor complementary DNA in 1
      tumor from family A was normal. There was no history of consanguinity in either
      family, and the past medical history and laboratory results excluded MEN-1 and
      the Carney complex in all affected and unaffected screened subjects. Five of 8
      subjects have undergone pituitary surgery to date, and paraffin-embedded
      pituitary blocks were available for analysis. Loss of heterozygosity on
      chromosome 11q13 was studied by comparing microsatellite polymorphisms of
      leukocyte and tumor DNA using PYGM (centromeric) and D11S527 (telomeric), markers
      closely linked to the MEN-1 tumor suppressor gene. All tumors exhibited a loss of
      heterozygosity at both markers. Sequencing of the MEN-1 gene revealed no germline
      mutations in either family, nor was a somatic mutation found in tumor DNA from
      one subject in family A. The integrity of the MEN-1 gene in this subject was
      further supported by demonstration of the presence of MEN-1 messenger ribonucleic
      acid, as assessed by RT-PCR. These data indicate that loss of heterozygosity in
      these affected family members appears independent of MEN-1 gene changes and
      suggest that a novel (tissue-specific?) tumor suppressor gene(s) linked to the
      PYGM marker and expressed in the pituitary is essential for regulation of
      somatotrope proliferation.

PMID- 9920091
TI  - Role of inflammatory mediators in human endometrium during progesterone
      withdrawal and early pregnancy.
AB  - The role of progesterone (P4) in the regulation of inflammatory mediators
      interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2
      (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has
      been examined, by employing a model of P4 withdrawal and maintenance in vivo.
      Messenger RNA and protein expression have been investigated in endometrial
      biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained
      luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies
      collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo
      pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua
      collected from women with 5) an ectopic gestation and 6) from women undergoing
      first-trimester termination of pregnancy). CD56+ large granular lymphocytes
      remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in
      decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages
      (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo
      pregnant endometrium, compared with normal decidua. Significantly more
      macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A
      significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was
      detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8
      and COX-2 in response to P4 withdrawal.

PMID- 9920093
TI  - Functional dopamine-1 receptors and DARPP-32 are expressed in human ovary and
      granulosa luteal cells in vitro.
AB  - The catecholamines norepinephrine and dopamine (DA) are present in the human
      ovary; in particular, in follicular fluid. Norepinephrine activates ovarian alpha
      and beta-adrenergic receptors and modulates ovarian steroidogenesis, but the
      significance of ovarian DA is unclear. We examined whether a DA receptor of the
      D1-subtype (D1-R) is present in human ovary and in cultured human granulosa
      luteal cells (GC). Using RT-PCR, we cloned complementary DNAs from adult human
      ovarian and GC messenger RNAs, which are identical to the human D1-R sequence. In
      ovarian sections, D1-R protein was identified (by immunohistochemistry) in
      granulosa cells of large antral follicles, cells of the corpus luteum, as well as
      in cultured GC. An immunoreactive band of approximately Mr 50,000 was found in
      cultured luteinized GC using the same antiserum in Western blots. The D1-R in
      these cells was functional, because DA, alone or in the presence of the beta
      receptor antagonist propranolol, caused cellular contraction. The selective D1-R
      agonist SKF-38393 induced a similar change in cytomorphology and increased the
      levels of media cAMP. SKF-38393 failed, however, to significantly affect basal
      and hCG-stimulated progesterone release in vitro, indicating that the activation
      of the D1-R was not directly linked to synthesis of progesterone, the major
      steroid of human GC. Estradiol synthesis likewise was not affected. Using RT-PCR
      and immunohistochemistry, we found that GC express DA- and cAMP-regulated
      phosphoprotein of Mr 32,000 (DARPP-32), a protein typically associated with
      neurons bearing the D1-R. In cultured GC, DA and SKF-38393 induced increased
      threonine-phosphorylation of DARPP-32, even in the presence of propranolol but
      not in the presence of D1-R antagonist SCH-23390. Taken together, the presence of
      DA and a functional DA receptor and DARPP-32 indicate that a novel, physiological
      regulatory pathway involving DA exists in the human ovary.

PMID- 9920094
TI  - Two antiatherogenic effects of progesterone on human macrophages; inhibition of
      cholesteryl ester synthesis and block of its enhancement by glucocorticoids.
AB  - The effects of progesterone and estradiol on cholesteryl ester (CE) formation by
      monocyte-derived human macrophages were examined. Formation was assessed from
      incorporation of 14C-cholesterol during a 20-h incubation with hormone and from
      that of 3H-oleate (3 h) after hormone removal. Progesterone inhibited cholesterol
      into CE and decreased CE cellular levels. Inhibition: 1) was reversed by
      progesterone removal; 2) was independent of the progesterone receptor (not
      blocked by the receptor antagonist RU40555); and 3) exhibited specific structural
      requirements; 11alpha-OH-progesterone was inhibitory, whereas its stereoisomer
      11beta-OH-progesterone was not. In contrast to progesterone, estradiol was
      ineffective. We had reported that dexamethasone enhanced CE accumulation by human
      macrophages (1). In this study, we describe similar effects of the endogenous
      steroid, cortisol, and of the most widely prescribed glucocorticoid,
      prednisolone. Both steroids increased CE formation from two folds, in the
      presence of cholesterol-liposomes, to five folds, in the presence of modified low
      density lipoprotein. Progesterone (0.1-1 micromol/L), added during glucocorticoid
      treatment, blocked this increase. The progesterone block: 1) was duplicated by
      the steroid receptor inhibitor RU40555; 2) was not reversed by hormone removal;
      and 3) reflected inhibition of glucocorticoid-induced increases in messenger RNA
      for acyl-CoA-cholesterol:acyl transferase. Thus, progesterone exerted two effects
      on macrophages: it acutely inhibited CE formation, and it prevented
      glucocorticoid-induced increases in acyl-CoA-cholesterol-acyl transferase gene
      expression and CE synthesis.

PMID- 9920095
TI  - Circulating tumor necrosis factor-alpha concentrations in a native Canadian
      population with high rates of type 2 diabetes mellitus.
AB  - Recent research suggests that tumor necrosis factor-alpha (TNF alpha) may play an
      important role in obesity-associated insulin resistance and diabetes. We studied
      the relationship between TNF alpha and the anthropometric and physiological
      variables associated with insulin resistance and diabetes in an isolated Native
      Canadian population with very high rates of type 2 diabetes mellitus (DM). A
      stratified random sample (n = 80) of participants was selected from a population
      based survey designed to determine the prevalence of type 2 DM and its associated
      risk factors. Fasting blood samples for glucose, insulin, triglyceride, leptin,
      and TNF alpha were collected; a 75-g oral glucose tolerance test was
      administered, and a second blood sample was drawn after 120 min. Insulin
      resistance was estimated using the homeostasis assessment (HOMA) model. Systolic
      and diastolic blood pressure (BP), height, weight, and waist and hip
      circumferences were determined, and percent body fat was estimated using
      biological impedance analysis. The relationship between circulating
      concentrations of TNF alpha and the other variables was assessed using Spearman
      correlation coefficients, analysis of covariance, and multiple linear regression.
      The mean TNF alpha concentration was 5.6 pg/mL (SD = 2.18) and ranged from 2.0
      12.9 pg/mL, with no difference between men and women (P = 0.67). There were
      moderate, but statistically significant, correlations between TNF alpha and
      fasting insulin, HOMA insulin resistance (HOMA IR) waist circumference, fasting
      triglyceride, and systolic BP (r = 0.23-0.34; all P < 0.05); in all cases,
      coefficients for females were stronger than those for males. Individuals with
      normal glucose tolerance had lower log TNF alpha concentrations than those with
      impaired glucose tolerance or type 2 DM (both P = 0.03, adjusted for age and
      sex), although differences were not significant after adjustment for HOMA IR
      (both P > 0.25). Regression analysis indicated that log HOMA IR and log systolic
      BP were significant independent contributors to variations in log TNF alpha
      concentration (model r2 = 0.32). We conclude that in this homogeneous Native
      Canadian population, circulating TNF alpha concentrations are positively
      correlated with insulin resistance across a spectrum of glucose tolerance. The
      data suggest a possible role for TNF alpha in the pathophysiology of insulin
      resistance.

PMID- 9920096
TI  - Changes in muscle volume, strength, and bioenergetics during recombinant human
      growth hormone (GH) therapy in adults with GH deficiency.
AB  - Adults with GH deficiency (GHD) suffer from muscle weakness, which can be caused
      by the frequently reported decrease in muscle mass. However, measurements of both
      muscle strength and mass of muscle tested are scarce in adults with GHD. The aim
      of the present study was, therefore, to investigate intrinsic muscle strength
      (strength expressed per muscle volume unit) in adults with GHD at baseline and
      after 52 weeks of recombinant human GH (rhGH) therapy given in low, more
      physiological doses. A second objective was to investigate the influence of GH on
      muscle bioenergetics in the resting muscle. Isometric and isokinetic quadriceps
      strengths were measured in 28 males with GHD and in healthy controls matched for
      age and height. Quadriceps mass, determined by magnetic resonance imaging, and
      muscle bioenergetics, determined by phosphorus nuclear magnetic resonance
      spectroscopy, were measured in 20 of 28 patients with GHD and in controls matched
      for age and height. All patients were treated with doses of rhGH ranging from 0.6
      1.8 IU/day, given for 52 weeks. Measurements of muscle mass, strength, and
      bioenergetics were repeated after 52 weeks of treatment with rhGH. The mean GH
      dose at 52 weeks of rhGH treatment was 1.3 +/- 0.8 IU/day. The mean serum insulin
      like growth factor I level at baseline was 9.4 +/- 0.7 nmol/L and significantly
      increased to 26.4 +/- 1.2 nmol/L after 52 weeks of rhGH treatment. Adults with
      GHD had significantly reduced quadriceps muscle mass (P = 0.034) and reduced
      isometric muscle strength (P = 0.002) and tended to have low isokinetic muscle
      strength (P = 0.06), which all improved after rhGH therapy. Intrinsic muscle
      strength was not significantly different in adults with GHD compared with that in
      healthy controls and did not change during rhGH therapy. No bioenergetic
      abnormalities at baseline or after rhGH therapy were found in males with GHD. In
      conclusion, quadriceps muscle mass is decreased in adults with GHD and increased
      with rhGH therapy. These changes in muscle mass account for the changes in muscle
      strength found in these patients, as no changes in intrinsic muscle strength were
      found.

PMID- 9920097
TI  - Effects of recombinant human insulin-like growth factor I administration on
      growth hormone (GH) secretion, both spontaneous and stimulated by GH-releasing
      hormone or hexarelin, a peptidyl GH secretagogue, in humans.
AB  - The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH
      secretion occurs at the pituitary, as well as the hypothalamic level, via
      stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human
      IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted
      humans, though its effect on the GH response to GHRH is still controversial. GH
      secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific
      receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the
      GH-releasing activity of GHS is strong, reproducible, and even partially
      refractory to inhibitory influences such as exogenous somatostatin. We studied
      the effects of rhIGF-I administration (20 microg/kg s.c. at 0 min) on GH
      secretion, either spontaneous or stimulated by GHRH (2 microg/kg i.v. at +180
      min) or Hexarelin (HEX, 2.0 microg/kg i.v at +180 min), a GHS, in eight normal
      young women (age, mean +/- SEM, 28.3 +/- 1.2 yr; body mass index, 20.1 +/- 0.5
      kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3
      +/- 30.5 vs. 274.4 +/- 25.3 microg/L, P < 0.05) within the physiological range
      from +120 to +300 min. No variation in glucose or insulin levels was recorded.
      rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)(0-300
      min) 140.6 +/- 66.3 vs. 114.6 +/- 32.1 microg/L x h], whereas it inhibited the GH
      response to both GHRH (AUC(180-300 min) 447.7 +/- 159.4 vs. 715.9 +/- 104.3
      microg/L x h, P < 0.05) and HEX (620.3 +/- 110.4 vs. 1705.9 +/- 328.9 microg/L x
      h, P < 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH
      (41.7 +/- 12.8%) was lower than that on the response to HEX (57.7 +/- 11.0%). In
      fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P <
      0.05), whereas the GH responses to GHRH and HEXwere similar after rhIGF-I. Our
      findings show that the sc administration of low rhIGF-I doses inhibits the GH
      response to GHRH and, even more, that to HEX; whereas, at least in this
      experimental design in fed conditions, it does not modify the spontaneous GH
      secretion. Because GHS generally show partial refractoriness to inhibitory
      inputs, including exogenous somatostatin, the present results point toward a
      peculiar sensitivity of GHS to the negative feedback action of IGF-I.

PMID- 9920098
TI  - Steroid regulation of prostaglandin dehydrogenase activity and expression in
      human term placenta and chorio-decidua in relation to labor.
AB  - NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic
      enzyme controlling levels of biologically active PGs. PGDH is localized to
      syncytiotrophoblast in placenta, and to trophoblast cells in chorion. To examine
      the regulation of PGDH by steroids and to determine any changes with labor, we
      obtained placenta and chorion from term elective cesarean section or spontaneous
      delivery and isolated trophoblast cells using a Percoll density gradient. Cells
      were treated with varying concentrations of cortisol, progesterone, the synthetic
      progestins R5020, and medroxyprogesterone acetate with or without RU486 or the
      specific progesterone receptor antagonist, onapristone, and the 3beta
      hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was
      assessed by measurement of 13,14-dihydro-15-keto-PGF2alpha. PGDH messenger
      ribonucleic acid was quantified by in situ hybridization and computerized image
      analysis. The basal output of 13,14-dihydro-15-keto-PGF2alpha was lower in
      placenta or chorion collected at spontaneous labor than in that obtained at
      elective cesarean section. Cortisol had a significant dose-dependent inhibitory
      effect on PGDH activity in both placental and chorion trophoblast cells and
      significantly decreased levels of PGDH messenger ribonucleic acid. Responses were
      similar between tissues from laboring and nonlaboring women. PGDH activity was
      increased by R5020 and medroxyprogesterone acetate and was inhibited by RU486,
      onapristone, and trilostane. We conclude that cortisol inhibits PGDH activity and
      expression and that progestagens increase PGDH activity in human chorion and
      placenta.

PMID- 9920099
TI  - Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic
      pregnancies.
AB  - We measured serum levels of free leptin, bound leptin, and soluble leptin
      receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes
      mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the
      data using hierarchical statistical models. Total leptin levels rise from 20-30
      weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There
      is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is
      caused by the rise in the bound leptin levels, as there is no significant change
      in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant
      postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in
      the third trimester, but despite this there was no significant difference in free
      or bound leptin levels between the normal and diabetic subjects at any stage
      [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/-
      16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78
      and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and
      diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic
      subjects, however, had significantly higher soluble leptin receptor levels at all
      stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268
      (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a
      fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship
      between the soluble leptin receptor levels and the body mass index in the
      diabetic group only. We conclude that there is no significant difference in free
      or bound leptin levels between the normal and insulin-dependent diabetic subjects
      either during pregnancy or postpartum, but female insulin-dependent diabetic
      subjects have significantly higher soluble leptin receptor levels. We speculate
      that high soluble leptin receptor levels might be implicated in the development
      of the leptin resistance in this group.

PMID- 9920100
TI  - Effects of growth hormone (GH) replacement therapy on very low density
      lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a
      stable isotope study.
AB  - Patients with adult GH deficiency are often dyslipidemic and may have an
      increased risk of cardiovascular disease. The secretion and clearance of very low
      density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants
      of plasma lipid concentrations. This study examined the effect of GH replacement
      therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL
      apoB kinetics were determined in 14 adult patients with GH deficiency before and
      after 3 months GH or placebo treatment in a randomized double blind, placebo
      controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB
      enrichment was determined by gas chromatography-mass spectrometry. GH replacement
      therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5
      fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and
      hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It
      decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by
      3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the
      low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL
      cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not
      significantly change the VLDL apoB pool size, but increased the VLDL apoB
      secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the
      MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes
      were observed in the placebo group. This study suggests that GH replacement
      therapy improves lipid profile by increasing the removal of VLDL apoB. Although
      GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the
      VLDL apoB clearance rate, which we postulate is due to its effects in up
      regulating low density lipoprotein receptors and modifying VLDL composition.

PMID- 9920101
TI  - Serum concentration of 20K human growth hormone (20K hGH) measured by a specific
      enzyme-linked immunosorbent assay. Study Group of 20K hGH.
AB  - Several GH isoforms have been identified in pituitary and serum, the most
      abundant of which is the 22K human GH (hGH) isoform. The 20K hGH isoform is
      produced by alternative splicing of GH messenger ribonucleic acid and comprises
      approximately 10% of all GH in the pituitary. The physiological role of 20K hGH
      remains to be determined, partly because of the lack of a simple and specific
      assay. We have established sensitive enzyme-linked immunosorbent assays (ELISAs)
      specific to 20K and 22K hGH. To determine whether regulation of 20K hGH secretion
      is the same as that for 22K hGH, we measured serum concentrations of both species
      of hGH in normal subjects and patients with a variety of endocrine disorders. The
      serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (n = 282)
      in normal women, significantly higher than that in normal men (64 +/- 170 pg/mL;
      n = 226). However, there was no difference in the proportion of 20K hGH to 20K
      plus 22K hGH between men (6.3 +/- 2.6%, mean +/- SD; n = 176) and women (6.3 +/-
      2.1%; n = 263). No correlation was detected between the ratio of 20K hGH and age,
      body height, body weight, or body fat mass in normal subjects. The proportion of
      20K hGH was significantly (P < 0.001) higher in patients with active acromegaly
      (9.2 +/- 2.2%; n = 33) and patients with anorexia nervosa (9.0 +/- 1.9; n = 8),
      both of which are characterized by chronic elevation of circulating GH levels.
      The proportion of 20K hGH in successfully treated acromegalic patients did not
      differ from that in normal subjects, suggesting that GH-producing pituitary
      tumors secrete a higher proportion of 20K hGH, or that a chronic excess of 22K
      hGH alters the MCR of 20K hGH. The values in patients with adult GH deficiency,
      hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not
      differ from those in normal subjects. The 20K ratio did not change after acute GH
      provocative tests, such as the insulin tolerance test and the GHRH test. These
      results suggest that secretion of 20K hGH from the pituitary is under the same
      control as that of 22K hGH. This new assay may provide a tool for understanding
      the physiological or pathophysiological role of the 20K hGH isoform.

PMID- 9920102
TI  - Decreased melatonin levels in postmortem cerebrospinal fluid in relation to
      aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype.
AB  - Sleep disruption, nightly restlessness, sundowning, and other circadian
      disturbances are frequently seen in Alzheimer's disease (AD) patients. Changes in
      the suprachiasmatic nucleus and pineal gland are thought to be the biological
      basis for these behavioral disturbances. Melatonin is the main endocrine message
      for circadian rhythmicity from the pineal. To determine whether melatonin
      production was affected in AD, melatonin levels were determined in the
      cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 +/- 1.1 yr) and in
      82 age-matched controls (mean age, 76 +/- 1.4 yr). Ventricular postmortem CSF was
      collected from clinically and neuropathologically well defined AD patients and
      from control subjects without primary neurological or psychiatric disease. In old
      control subjects (>80 yr of age), CSF melatonin levels were half of those in
      control subjects of 41-80 yr of age [176 +/- 58 (n = 29) and 330 +/- 66 (n = 53)
      pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF
      melatonin levels in control subjects. In AD patients the CSF melatonin levels
      were only one fifth (55 +/- 7 pg/mL) of those in control subjects (273 +/- 47
      pg/mL; P = 0.0001). There was no difference in the CSF melatonin levels between
      the presenile (42 +/- 11 pg/mL; n = 21) and the senile (59 +/- 8 pg/mL; n = 64; P
      = 0.35) AD patients. The melatonin level in AD patients expressing apolipoprotein
      E-epsilon3/4 (71 +/- 11 pg/mL) was significantly higher than that in patients
      expressing apolipoprotein E-epsilon4/4 (32 +/- 8 pg/ml; P = 0.02). In the AD
      patients no significant correlation was observed between age of onset or duration
      of AD and CSF melatonin levels. In the present study, a dramatic decrease in the
      CSF melatonin levels was found in old control subjects and even more so in AD
      patients. Whether supplementation of melatonin may indeed improve behavioral
      disturbances in AD patients should be investigated.

PMID- 9920103
TI  - DRB1*04 and DQ alleles: expression of 21-hydroxylase autoantibodies and risk of
      progression to Addison's disease.
AB  - Of 957 patients with type 1 diabetes without known Addison's disease 1.6% (n =
      15) were positive for 21-hydroxylase autoantibodies. Among DQ8/DQ2 heterozygous
      patients, the percentage expressing 21-hydroxylase autoantibodies was 5% (10 of
      208) vs. less than 0.5% of patients with neither DQ8 nor DQ2. Three of the
      diabetic patients found to have 21-hydroxylase autoantibodies on screening were
      subsequently diagnosed with Addison's disease. Overall, the genotype DQ8/DQ2,
      consisting of DRB1*0404/DQ8 with DRB1*0301/DQ2, was present in 14 of 21 patients
      with Addison's disease (8 of 12 with diabetes and 6 of 9 without diabetes or
      antiislet autoantibodies) vs. 0.7% of the general population (109 of 15,547; P <
      10(-6)) and 11% of patients with DM without Addison's disease (62 of 578; P < 10(
      6)). Among patients with diabetes with DQ8, Addison's disease was strongly
      associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8
      families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without
      Addison's disease having DRB1*0404; P < 0.001). Among 21-hydroxylase autoantibody
      positive DQ8 patients, 80% with DRB1*0404 (12 of 15) had Addison's disease, in
      contrast to 1 of 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P
      < 0.001). We conclude that patients with DRB1*0404 and 21-hydroxylase
      autoantibodies are at high risk for Addison's disease. Patients with DRB1*0401
      and DRB1*0402 have more limited progression to Addison's disease despite the
      presence of 21-hydroxylase autoantibodies.

PMID- 9920104
TI  - Phenocopies for deafness and goiter development in a large inbred Brazilian
      kindred with Pendred's syndrome associated with a novel mutation in the PDS gene.
AB  - Pendred's syndrome is an autosomal recessive disease characterized by goiter,
      impaired iodide organification, and congenital sensorineural deafness. The gene
      mutated in Pendred's syndrome, PDS (Pendred's syndrome gene), was cloned very
      recently and encodes the putative sulfate transporter pendrin. Pendred's syndrome
      may account for up to 10% of the cases with hereditary hearing loss, and pendrin
      mutations have also been found in a kindred with non-syndromic deafness. In this
      study, 41 individuals from a large, highly inbred pedigree from Northeastern
      Brazil were examined for features of Pendred's syndrome. Linkage studies and
      sequence analysis of the coding region of the PDS gene were performed with DNA
      from 36 individuals. The index patient, with the classical triad of deafness,
      positive perchlorate test, and goiter, was found to be homozygous for a deletion
      of thymidine 279 in exon 3, resulting in a frameshift and a premature stop codon
      at amino acid 96. This alteration resulted in truncation of the protein in the
      first transmembrane domain. Two other patients with deafness were found to be
      homozygous for this mutation; 19 were heterozygous and 14 were homozygous for the
      wild type allele. Surprisingly, 6 deaf individuals in this kindred were not
      homozygous for the PDS gene mutation; 3 were heterozygous and 3 were homozygous
      for the wild type allele, suggesting a probable distinct genetic cause for their
      deafness. All 3 homozygous individuals for the PDS mutation had goiters. However,
      goiters were also found in 10 heterozygous individuals and in 6 individuals
      without the PDS mutation and are most likely caused by iodine deficiency. In
      conclusion, we identified a novel mutation in the PDS gene causing Pendred's
      syndrome. The comparison of phenotype and genotype reveals, however, that
      phenocopies generated by distinct environmental and/or genetic causes are present
      in this kindred and that the diagnosis of Pendred's syndrome may be difficult
      without molecular analysis.

PMID- 9920105
TI  - Titrating luteinizing hormone replacement to sustain the structure and function
      of the corpus luteum after gonadotropin-releasing hormone antagonist treatment in
      rhesus monkeys.
AB  - These studies were designed to identify 1) a regimen of a third generation GnRH
      antagonist that abolishes primate luteal function, and 2) the amount of LH
      replacement required to maintain the structure and functional life span of the
      corpus luteum of the menstrual cycle after GnRH antagonist treatment. A single
      injection of antide at 3 or 5 mg/kg BW on day 6 of the luteal phase suppressed
      serum progesterone levels within 1 day of treatment, but levels recovered within
      4 days. Administration of antide (3 mg/kg) for 3 days (luteal days 6-8) reduced
      (P < 0.05) serum progesterone below 1 ng/mL and maintained these low levels for
      the entire sampling period; in subsequent experiments, all monkeys received this
      antide regimen. Fixed doses (5, 10, or 20 IU) of recombinant human LH
      administered at 8-h intervals during and after antide treatment stimulated
      progesterone production in a dose-dependent manner; these monkeys menstruated
      earlier than controls regardless of treatment group. Replacement with an
      escalating dose regimen (5-20 IU) of LH resulted in typical serum progesterone
      and relaxin levels throughout a luteal phase of normal length. Corpora lutea
      removed on day 10 from monkeys treated with antide alone had decreased wet weight
      (P < 0.05) and few large luteal cells; coadministration of the escalating dose
      regimen of LH maintained luteal structure similar to that seen in time-matched
      controls. Antide-only treatment increased progesterone receptor (PR) messenger
      ribonucleic acid, but decreased PR immunostaining in luteal tissue; the
      escalating dose regimen of LH maintained PR messenger ribonucleic acid and
      immunostaining similar to those in controls. This study indicates that during
      GnRH antagonist administration, an escalating dose regimen of LH replacement is
      optimal for maintenance of the structure and functional life span of the primate
      corpus luteum.

PMID- 9920106
TI  - Androgen receptor distribution in adult human testis.
AB  - The distribution of the androgen receptor (AR) in archival human testes was
      determined immunocytochemically using an affinity-purified peptide-specific
      rabbit antibody, PG21, and employing a modified biotin-streptavidin
      immunoperoxidase method that incorporated a biotin amplification step. In
      combination with microwave epitope retrieval, the biotin amplification step
      increased the sensitivity of the immunostaining assay approximately 20-fold.
      Thus, the useful range at which PG21 rendered a robust, specific immunostaining
      signal without also increasing nonspecific background was extended dramatically.
      Broadening the useful range of the PG21 antibody made it possible to resolve the
      relative amounts of immunopositive AR in different cell types of the human
      testis. At a high PG21 concentration, for example, all AR-positive cells
      exhibited a robust immunostaining intensity, but it was not possible to
      distinguish between nuclei exhibiting either high or moderate immunostaining
      intensities. In contrast, as the concentration of PG21 was decreased, distinct
      populations of testicular cells exhibited differential AR immunostaining
      intensities in their nuclei. AR immunostaining of Sertoli cell nuclei was present
      at low PG21 concentrations at which no immunostaining of peritubular myoid cells
      or Leydig cells could be detected. In turn, AR immunostaining of peritubular
      myoid cells was detected at PG21 concentrations that did not immunostain Leydig
      cells. Moreover, within the seminiferous epithelium, Sertoli cell nuclear AR
      staining intensity was less at stages V and VI of the cycle of the seminiferous
      epithelium than that at stage III, and stage III staining intensity was greater
      than that at stages I and II. This AR immunostaining pattern in human Sertoli
      cell nuclei as a function of the cycle of the seminiferous epithelium is
      reminiscent of the pattern observed in rodent species. Finally, no AR
      immunostaining of germ cells was observed at any of the PG21 concentrations
      examined.

PMID- 9920107
TI  - Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related
      to angiogenesis in ovarian endometriosis.
AB  - Platelet-derived endothelial cell growth factor (PD-ECGF) is expressed in the
      lining epithelial cells of ovarian endometriomas, and in interstitial cells of
      the subepithelial area with angiogenesis. The expression of PD-ECGF persists in
      endometriotic endometrium during the menstrual cycle. This might suggest that PD
      ECGF contributes to the growth of ovarian endometriomas via subepithelial
      angiogenesis independently of the sex steroidal milieu.

PMID- 9920108
TI  - A novel activating mutation in calcium-sensing receptor gene associated with a
      family of autosomal dominant hypocalcemia.
AB  - Autosomal dominant hypocalcemia (ADH), caused by activating mutations of the
      calcium-sensing receptor (CaSR), is characterized by hypocalcemia with an
      inappropriately low concentration of PTH. Among 11 missense mutations of CaSR
      reported to date in patients with ADH or sporadic hypocalcemia, functional
      properties of 8 mutant CaSRs were characterized. Here, we describe a novel
      mutation of CaSR and its functional property in a family with ADH. The 41-yr-old
      male proband had asymptomatic hypocalcemia with a history of recurrent
      nephrolithiasis. His father had asymptomatic hypocalcemia, but his mother was
      normocalcemic. PCR-single strand conformation polymorphism and sequencing
      revealed that both the proband and the father had a novel heterozygous mutation
      in CaSR gene that causes lysine to asparagine substitution at codon 47 (K47N),
      which is in the extracellular domain of CaSR, like 6 of 11 known activating
      mutations. Using HEK293 cells transfected with wild-type or K47N CaSR
      complementary DNA, the intracellular Ca2+ concentration was assessed in response
      to changes in the extracellular Ca2+ concentration. The EC50 of the mutant CaSR
      for the extracellular Ca2+ concentration was 2.2 mmol/L and was significantly
      lower than that of wild-type (3.7 mmol/L). These results confirm that this
      mutation is responsible for ADH in this family. The fact that several
      inactivating mutations in familial hypocalciuric hypercalcemia occur in amino
      acid around K47 suggests the importance of the N-terminal portion of the receptor
      in extracellular Ca sensing.

PMID- 9920109
TI  - A novel Phe75fsdelT mutation in the hepatocyte nuclear factor-4alpha gene in a
      Danish pedigree with maturity-onset diabetes of the young.
AB  - Mutations in 5 different genes [the hepatocyte nuclear factor (HNF)-4alpha),
      glucokinase, HNF-1alpha, insulin promoter factor-1, and HNF-1beta genes] have
      been shown to cause maturity onset diabetes of the young (MODY). About 50% of all
      known MODY in Danish Caucasian MODY probands can be explained by mutations in the
      HNF-1alpha gene (MODY3). To estimate the prevalence of MODY caused by mutations
      in the HNF-4alpha gene (MODY1), we screened 10 non-MODY3 probands for mutations
      in the minimal promoter and the 12 exons of the HNF-4alpha gene. One of the
      probands had a novel frameshift mutation (Phe75fsdelT) in exon 2 of the HNF
      4alpha gene, resulting in a premature termination of translation after 117 amino
      acids of the messenger RNA encoded by that allele. The mutation cosegregated with
      diabetes in the pedigree and was not detected in 84 unrelated Danish Caucasian
      healthy glucose-tolerant control subjects or in 84 type 2 diabetic patients. At
      the time of examination, 4 of 6 mutation carriers were treated with insulin and 2
      with oral hypoglycemic medication. Two mutation carriers had late-diabetic
      complications. Even though the HNF-4alpha protein is known to be important in the
      regulation of genes involved in lipid metabolism, carriers of the mutation did
      not differ from age and sex-matched control subjects, in regard to levels of
      fasting serum total cholesterol, serum high-density lipoprotein-cholesterol, and
      serum triglyceride. In conclusion, by screening 10 non-MODY3 probands for
      mutations in the HNF-4alpha gene, we identified 1 diabetes-associated frameshift
      mutation (Phe75fsdelT), suggesting that defects in HNF-4alpha are a rare cause of
      MODY in Denmark.

PMID- 9920110
TI  - Demonstration of estrogen receptor-beta immunoreactivity in human growth plate
      cartilage.
AB  - Estrogens affect longitudinal bone growth through their action on endochondral
      bone formation. Two estrogen receptors are known, the classical estrogen receptor
      alpha (ER alpha), newly demonstrated in human growth plate cartilage, and a
      recently cloned estrogen receptor-beta (ER beta). The present study aimed to
      localize a possible expression of ER beta protein in human growth plates. Tissue
      samples were obtained from tibial and femoral growth plates in four female
      pubertal patients undergoing epiphyseal surgery. Immunohistochemistry, using two
      different ER beta-specific antibodies, demonstrated positive staining for ER beta
      in hypertrophic epiphyseal chondrocytes from all patients. No staining was noted
      in resting or proliferative chondrocytes. These data suggest that in addition to
      ER alpha, human epiphyseal chondrocytes also express ER beta. The physiological
      role of ER beta in the regulation of longitudinal bone growth in humans remains
      to be elucidated.

PMID- 9920111
TI  - Development of a luminescent bioassay for thyroid stimulating antibodies.
AB  - The hyperthyroidism of Graves Disease (GD) is due to thyroid stimulating
      antibodies (TSAb) which are thyrotropin (TSH) agonists. They are detected
      routinely by measuring their ability to inhibit TSH binding to the receptor
      (TBII), which does not reflect their true biological activity. Current bioassays
      which measure cAMP by RIA, are not suitable for routine use. We have developed a
      luminescent bioassay for TSAb, by introducing a cAMP responsive luciferase
      construct into CHO cells stably expressing the human TSH receptor (TSHR). Clone
      lulul displays dose dependent TSH response detectable from 10 microU/ml and
      maximal at 10 mU/ml when a >25 fold increase in light output is obtained. 34
      euthyroid sera were tested to determine a reference range, with values >1.5
      relative light units (R.L.U.) being considered positive. An international TSAb
      standard responded in a dose dependent manner with 10 mIU/ml giving an R.L.U. of
      >10. The assay was adapted to a 96 well format for automatic readout and 100
      treated GD samples (50 TBII negative and 50 TBII positive) were tested, 73% being
      positive. In contrast only 4% of 79 control sera from individuals with
      Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U.
      >1.5. When 44 of the GD sera were compared in a traditional salt-free bioassay,
      61% were positive compared with 75% in the new luminescent assay. In conclusion,
      we have developed a luminescent bioassay for TSAb, using unfractionated serum
      which is capable of high throughput suitable for routine use.

PMID- 9920112
TI  - Congenital adrenal hyperplasia (21-hydroxylase deficiency) without demonstrable
      genetic mutations.
AB  - Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD)
      is the most common inherited defect of adrenal steroid biosynthesis. At least 36
      mutations in the CYP21 gene, which is mapped to chromosome 6p21.3, have been
      described. We performed genetic analysis of the CYP21 gene in a patient with
      classic 21-OHD CAH and her family. The entire exonic coding regions and intronic
      regions, as well as the -1 kb 5' upstream promoter region, were thoroughly
      sequenced and analyzed. Despite extensive sequencing, no mutation was found in
      this 3.7 kb area. The 11beta-hydroxylase defect, closely mimicking the clinical
      and biochemical phenotype of classic 21-OHD, was excluded by directly sequencing
      2.6 kb covering the entire coding of the CYP11B1 gene. Herein we describe a
      phenotypically and hormonally affected patient with classic simple virilizing 21
      OHD CAH who lacks a mutation in the entire CYP21 gene and coding region of the
      CYP11B1 gene.

PMID- 9920113
TI  - Further arguments for a functional difference between pituitary corticotroph
      macroadenomas and microadenomas.

PMID- 9920114
TI  - Comment on glucose-to-insulin ratio as a measure of insulin sensitivity in women
      with PCOS. Polycystic ovary syndrome.

PMID- 9920115
TI  - Comment on effect of large doses of aspartame on urinary calcium excretion.

PMID- 9920116
TI  - Hyperparathyroidism and increased serum IGF-binding protein-2 levels in hepatitis
      C-associated osteosclerosis.

PMID- 9920117
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 9920118
TI  - Prospects for therapeutic Helicobacter pylori vaccines.

PMID- 9920119
TI  - Advantage of recombinant borrelial proteins for serodiagnosis of
      neuroborreliosis.
AB  - Two enzyme immunoassay (EIA) systems were compared for their ability to detect
      Borrelia burgdorferi sensu lato specific IgG and IgM antibodies and to
      differentiate between symptomatic (83 patients with neuroborreliosis) and
      asymptomatic seropositive subjects (80 healthy controls). Antibody concentrations
      were determined by EIA; the antigens used were either a sonicate of B.
      burgdorferi or three recombinant borrelial proteins: the 14-kDa flagellin
      fragment, the outer surface protein C (22 kDa) and the high molecular mass
      protein p83 (83 kDa). In the sonicate, EIA, IgG or IgM antibodies to B.
      burgdorferi, or both, were detected in all patients with neuroborreliosis and in
      all controls. Pre-absorption of sera with Treponema phagedenis sonicate
      diminished the sensitivity of detection of borrelial specific IgG (IgG or IgM or
      both) antibodies in patients with neuroborreliosis from 80 to 57% (100 to 82%)
      and in the controls from 100 to 32% (100 to 37%). While being specific for B.
      burgdorferi, the recombinant EIAs proved to be significantly more sensitive than
      the sonicate EIA: IgG or IgM, or both antibodies against any of the recombinant
      antigens were detected in 92% of patients with neuroborreliosis and in 24% of
      controls. The increase in sensitivity in patients with neuroborreliosis was
      mostly due to the higher detection rate of IgM antibodies in the recombinant EIA
      (77% versus 48% in the sonicate EIA), while IgG antibodies were demonstrated with
      similar frequencies in both EIA systems (57% versus 60%). It was concluded that
      the recombinant EIAs are superior to the sonicate EIA with pre-absorption of
      cross-reactive antibodies in the confirmation of an acute borrelial infection and
      in the differentiation between symptomatic and asymptomatic infections.

PMID- 9920120
TI  - Antibodies to Shiga toxin in the serum of children with Shigella-associated
      haemolytic uraemic syndrome.
AB  - Antibodies to Shiga toxin (Stx) were measured in the sera of 49 children with
      Shigella dysenteriae serotype 1 infection, of whom 17 had haemolytic uraemic
      syndrome (HUS) and 32 had no complications (uncomplicated shigellosis, UCS).
      Children with HUS had lower levels of total IgG and IgM and lower IgM titres to
      Stx than those with UCS. The number of children with neutralising antibodies was
      similar in the two groups. Of the children with HUS, 11 had HUS on enrolment and
      six developed HUS subsequent to enrolment. Antibody titres in children who
      subsequently developed HUS were compared with those in children with UCS to
      assess whether differences in antibody titres occurred before the development of
      HUS. IgA titres to Stx were found to be higher in children who subsequently
      developed HUS than in those with UCS. However, logistic regression analysis
      revealed that titres of Stx antibodies in the serum were not significant risk
      factors for the development of HUS. Thus, although the levels of Stx antibodies
      were different in children with HUS, and higher IgA titres to Stx were
      identifiable in children who subsequently developed HUS compared with those with
      UCS, the relevance of these findings in the development of HUS remains to be
      elucidated.

PMID- 9920122
TI  - Characterisation of a 5.5-kb cryptic plasmid present in different isolates of
      Bacteroides spp. originating from Hungary.
AB  - The plasmid profiles of 97 Bacteroides isolates collected during screening for
      different pathogenic markers of this genus were investigated. In all, 48% of 69
      isolates from infections that belonged to six species harboured low mol.wt
      plasmids (2.8-11.0 kb). Similar plasmids were also found in 39% of 28 isolates,
      belonging to eight species, from faeces of healthy persons. The two most
      frequently obtained types were the 5.5- and the 4.2-kb plasmids, which were
      present in 70% and 52% of all plasmid-bearing isolates, respectively. Restriction
      endonuclease analysis revealed that the 5.5-kb plasmids found in the different
      Bacteroides spp. exhibited the same restriction map, with the exception that
      pBVP61 lacked the PstI recognition site. The two plasmid types (4.2 and 5.5 kb)
      seem to be most widely distributed among Bacteroides isolates independent of the
      site of isolation and with some differences depending on geographic regions.

PMID- 9920121
TI  - DNA typing of methicillin-resistant Staphylococcus aureus: isolates and factors
      associated with nosocomial acquisition in two Brazilian university hospitals.
AB  - Control and prevention of methicillin-resistant Staphylococcus aureus (MRSA)
      infections should include early identification of patients at higher risk of MRSA
      acquisition and analysis of isolates by discriminatory bacterial DNA typing
      methods. One hundred and three MRSA isolates cultured between Sept. 1994 and
      Sept. 1995 from 62 patients in two teaching hospitals (hospital 1, in Rio de
      Janeiro; hospital 2, in Minas Gerais) were tested for antimicrobial resistance
      and genomic DNA was analysed by pulsed-field gel electrophoresis (PFGE). Ten
      profiles were identified: A, B, C, I and J in hospital 1 and A, B, D, E, F, G and
      H in hospital 2. PFGE patterns A and B were isolated at both hospitals. The
      majority (80%) of isolates had similar PFGE patterns (type A). Subtype A1 was
      isolated at both hospitals, but was more frequent in hospital 2 (54%), while
      subtype A2 predominated in hospital 1 (63%). MRSA isolates were resistant to the
      majority of antimicrobial agents tested. However, susceptibility to vancomycin
      alone was found in 32% of the isolates at hospital 1, whereas 48% of isolates
      from hospital 2 were susceptible to both vancomycin and mupirocin, and 34%
      demonstrated susceptibility to vancomycin, mupirocin and chloramphenicol. Thirty
      nine percent of all isolates were mupirocin-resistant, with 90% of these
      belonging to PFGE pattern A. Four main risk factors were associated with MRSA
      infection or colonisation which may be useful in the early identification of
      patients at risk: >7 days hospitalisation (95%), very dependent patients (84%),
      invasive procedures (79%) and recent antimicrobial therapy (79%). The data
      demonstrate that PFGE pattern A is disseminated in both hospitals. However, at
      both hospitals subtypes of pattern A and the other PFGE types were associated
      with different antibiotic resistance patterns.

PMID- 9920123
TI  - Application of molecular typing methods to dermatophyte species that cause skin
      and nail infections.
AB  - Typing methods utilising DNA technology were applied to a collection of
      Trichophyton mentagrophytes and T. rubrum isolates from skin and nail infections.
      The methods included restriction enzyme analysis (REA), hybridisation with the
      DNA probe poly (dG-dT), randomly amplified polymorphic DNA (RAPD) by PCR and
      restriction analysis of a segment of PCR-amplified rDNA. All these tests
      successfully differentiated the species, but few intra-species differences were
      detected. REA demonstrated some isolate variation, but this was limited and
      difficult to interpret, making it unsuitable as a typing tool. RAPD demonstrated
      few variations amongst T. mentagrophytes and none in T. rubrum.

PMID- 9920124
TI  - Virulence properties of atypical EPEC strains.
AB  - Virulence properties of 31 atypical enteropathogenic Escherichia coli (EPEC)
      strains isolated from cases of diarrhoea were examined. All except two strains
      adhered to HEp-2 cells in a localised adherence-like (LAL) pattern. With the
      exception of two strains, all were fluorescent actin staining (FAS) positive.
      Gentamicin HEp-2 invasion assay studies showed that all strains were invasive.
      Transmission electron microscopy of infected HEp-2 cells showed the
      characteristic attaching and effacing lesion and invasion of the cultured cells.
      Of the nine strains that hybridised with a DNA probe for alpha-haemolysin, five
      were haemolytic within 3 h of incubation, while the remaining strains were
      haemolytic only after incubation for 24 h. Three strains produced
      enterohaemolysin on blood agar. None of the 31 strains of E. coli induced fluid
      accumulation in the rabbit intestinal loop assay or displayed cytotoxic effects
      in HeLa and Vero cells. All the strains belonging to serotypes O26:H11, O26:H-
      and 0119:H2 expressed intimin beta, whereas all the strains from serotype O55:H7
      expressed intimin gamma. The strains belonging to serogroup O111 expressed a non
      typable intimin. The participation of intimin in LAL was supported by adhesion
      inhibition experiments in which antibodies to intimin significantly reduced the
      level of LAL.

PMID- 9920125
TI  - Response of wild-type mutants of Vibrio cholerae O1 possessing different
      combinations of virulence genes in the ligated rabbit ileal loop and in Ussing
      chambers: evidence for the presence of additional secretogen.
AB  - Five wild-type mutant strains of Vibrio cholerae serogroup O1 that lacked the CTX
      virulence cassette, or contained a natural deletion of a virulence gene within
      the CTX virulence cassette, or possessed an additional virulence gene, along with
      a prototype toxigenic strain representing the El Tor classical biotypes were
      examined by in-vivo and in-vitro methods to determine their enterotoxic
      potential. The ability of whole cells and culture supernates of the strains to
      cause fluid accumulation in the rabbit ileal loop model revealed a pattern
      consistent with the presence of the various virulence gene(s), with those
      possessing the intact CTX virulence cassette being the most secretogenic. Culture
      supernates of strains without the CTX virulence cassette or the strain with an
      incomplete cassette were also able to evoke mild to moderate fluid accumulation
      in the rabbit ileal loop. Of the various media used, AKI and brain heart infusion
      broth appeared to support the production of a hitherto unknown secretogenic
      factor, because culture supernates of the non-toxigenic V. cholerae O1 strains
      showed higher fluid accumulation ratios when grown in these media than in the
      others. To confirm that the fluid accumulation elicited by these strains in the
      ileal loop was due to enterotoxin activity, the effect of supernate of the
      strains was examined in rabbit small intestine mounted on Ussing chambers.
      Increases in short circuit current and tissue conductance, as compared with the
      medium control, were observed even with the strains that did not possess the CTX
      virulence cassette, confirming their ability to disrupt the function of
      intestinal tissue. From these studies, it was concluded that strains of V.
      cholerae O1 devoid of the CTX virulence cassette were still able to elicit a
      secretory response in the ileal loop and displayed enterotoxic activity in an in
      vitro experimental model.

PMID- 9920126
TI  - Isolation of Borrelia burgdorferi from ticks in the Highlands of Scotland.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, was first isolated in
      1982 and since then has been regularly isolated from ticks and clinical material
      in both Continental Europe and the USA. However, only three isolations have been
      reported in Britain. During the summer of 1997, 128 ticks were collected from two
      sites in the Highlands of Scotland and examined by the polymerase chain reaction
      (PCR) and culture. Eleven fresh isolates were obtained from culture and passed up
      to 22 times. Seven of the tick emulsions were also positive by flagellin gene
      PCR, and a further one was positive by PCR but negative on culture. All 11
      isolate cultures were positive by the flagellin gene PCR. Further studies on four
      of these isolates confirmed their identity by immunofluorescence, but also
      detected possible differences between them and B. burgdorferi ACA-1 by enzyme
      profiles and by PCR with OspA gene primers. Culture of these new strains provides
      antigens that should improve diagnostic serological tests in Britain.

PMID- 9920127
TI  - Antibiotic resistance patterns among blood culture isolates in a Danish county
      1981-1995.
AB  - All episodes of bacteraemia during a 15-year period (1981-1995) in the County of
      Northern Jutland, Denmark, were analysed with regard to antibiotic resistance. A
      total of 8840 isolates from 7938 episodes of bacteraemia was identified. Over
      time, no changes in bacterial aetiology were noted. Three isolates of
      Staphylococcus aureus were methicillin resistant (0.2%) and six were gentamicin
      resistant (0.4%). Among coagulase-negative staphylococci a 14% increase in
      resistance to penicillin was observed (95% confidence intervals, CI: 2-26%).
      Likewise, the frequency of resistance to methicillin, gentamicin and erythromycin
      increased, the corresponding figures being 38% (CI: 26-50%), 26% (CI: 14-38%) and
      32% (CI: 16-50%), respectively, whereas a 14% decrease in resistance to
      streptomycin was recorded (CI: 4-24%). A 20% (CI: 2-37%) increase of coagulase
      negative staphylococci resistant to three or more antibiotics was observed. The
      frequency of ampicillin resistance increased by 9% among Escherichia coli (CI: 4
      13%) and by 10% (CI: 6-14%) in all Enterobacteriaceae. Among Enterobacteriaceae
      the level of resistance to third-generation cephalosporins, carbapenems,
      aminoglycosides and fluoroquinolones remained low (<1%). The frequency of
      resistance to three or more antibiotics remained fairly stable among
      Enterobacteriaceae, although a slight increase was noted among E. coli (5%; CI: 0
      10%) The recommended regimen for empirical antibiotic treatment in this region (a
      combination of penicillin G or ampicillin and an aminoglycoside) provided an
      overall coverage of 94% (CI: 94-95%), although a slight decrease was noted at the
      end of the period. In conclusion, acquired antibiotic resistance was maintained
      at a low level compared with most other European countries and regions during the
      15-year period studied.

PMID- 9920128
TI  - Analysis of mutations to gyrA in quinolone-resistant clinical isolates of
      Enterobacter cloacae.
AB  - The gyrA subgenes of a quinolone-resistant Enterobacter cloacae clinical isolate
      (ofloxacin MIC, 16 mg/L) and of a control, E. cloacae NCTC 10005 (ofloxacin MIC,
      0.03 mg/L), were amplified by polymerase chain reaction (PCR) and sequenced. The
      resistant isolate had mutations at the codons for amino acids 83, 89 and 90. The
      first of these mutations led to replacement of serine-83 by tyrosine, whereas the
      other mutations were silent. Digestion of PCR-amplified DNA fragments with the
      restriction enzyme HinfI detected mutations at the same site in gyrA in six
      further quinolone resistant E. cloacae isolates.

PMID- 9920129
TI  - Induction of systemic and mucosal immune response in mice immunised with porins
      of Salmonella typhi.
AB  - Porins, purified from Salmonella typhi strain 0901 provided 90% protection to
      BALB/c mice against a lethal dose (300 x LD50) of S. typhi Ty2 when given
      intraperitoneally. To measure the porin-induced cellular immune responses,
      macrophages and lymphocytes were isolated from spleen and lamina propria (LP) of
      porin immunised-challenge mice and of infected and control mice; T-cell
      phenotypes, lymphocyte proliferation and cytokine production were studied. The
      secretory IgA (sIgA) antibody level in the intestinal fluid was also measured to
      study mucosal immune response. After immunisation, the splenic lymphocytes
      exhibited a significant increase in total T-cell count and CD4+/CD8+ ratio, while
      the LP lymphocytes (LPL) exhibited an increase in CD4+/CD8+ ratio only. They also
      exhibited a significant increase in porin-specific proliferative response and
      cytokine levels (IL-1, IL-2, IFN-gamma and IL-4). After immunisation, sIgA
      antibody was also found to be increased. These results suggest that porins given
      intraperitoneally induce cellular and humoral immune responses both at systemic
      and mucosal levels.

PMID- 9920130
TI  - Oligofructose contributes to the protective role of bifidobacteria in
      experimental necrotising enterocolitis in quails.
AB  - Bifidobacteria are dominant in the gut of full-term infants, although
      colonisation by them is often delayed in preterm neonates. Bifidobacteria are
      recognised to have beneficial effects on digestive disorders and they might
      prevent neonatal necrotising enterocolitis (NEC), a gastrointestinal disease that
      predominantly affects premature infants. They have been shown to protect
      gnotobiotic quails against NEC-like lesions when the birds were inoculated with
      faecal flora from preterm infants, decreasing the clostridial population. The
      present study was designed to investigate whether oligofructose, which stimulates
      the activity of bifidobacteria, may enhance their protective role. Experiments
      were done in eight groups of germ-free quails for 28 days. The groups differed as
      to their bacterial status, diet and environment. Quails were inoculated with one
      of two flora from premature twins. The first flora included Bifidobacterium
      pseudo-catenulatum, Escherichia coli and no clostridia. The second flora included
      clostridial species and was associated with B. infantis-longum. Caecal bacterial
      population and metabolism changes were investigated with a lactose (6%) diet
      versus a lactose-oligofructose (3%-3%) diet, either in a gnotobiotic environment
      or in an ordinary environment permitting post-colonisation by exogenous bacteria.
      In both environments and with both flora, oligofructose significantly increased
      the level of bifidobacteria and this was associated with a decrease of E. coli or
      C. perfringens and C. ramosum. The bacterial changes in the ordinary environment
      depended on the initial composition of the microflora and the colonisation
      resistance against exogenous bacteria was more efficient with the flora that
      included B. pseudo-catenulatum. The changes in caecal pH and short-chain fatty
      acids were minimal. It was demonstrated that, irrespective of the environmental
      conditions, the use of oligofructose helped to prevent the overgrowth of bacteria
      implicated in necrotising enterocolitis in preterm neonates.

PMID- 9920131
TI  - Time-course of infection and responses in a coughing rat model of pertussis.
AB  - Adult female Sprague-Dawley rats were challenged intrabronchially with Bordetella
      pertussis strain 18-323 embedded in fine agarose beads and the time-course of
      infection and other events was determined. There was a steady decline in the
      numbers of B. pertussis recovered from the rat lungs, with clearance of the
      infection in most animals by day 12. Leucocytosis, lung inflammation and an
      increase in total serum IgE in the rats as a result of the challenge were highest
      around day 10, which was coincident with the highest incidence of coughing in
      such animals. IgG and IgA antibodies to the B. pertussis antigens pertussis toxin
      and filamentous haemagglutinin were not detected until after this period. The
      coughing rat model of pertussis resembles the human disease in the relationship
      between the time course of infection and cough production.

PMID- 9920132
TI  - Detection of circulating antigen in amoebic liver abscess by counter-current
      immunoelectrophoresis.
AB  - Fifty serum samples from patients with amoebic liver abscess and 50 from subjects
      who had not suffered from the disease (25 from patients with other, chiefly
      parasitic, infections and 25 from healthy blood donors, staff or students) were
      tested for circulating amoebic antigen by counter-current immuno-electrophoresis
      (CIEP). Amoebic antigen was detected in 38 sera (76%) from cases of amoebic liver
      abscess, but in none of the other sera. Although CIEP is only moderately
      sensitive, the high specificity suggests that this simple test may be useful in
      the diagnosis of amoebic liver abscess.

PMID- 9920133
TI  - Aerobic and anaerobic microbiology of axillary hidradenitis suppurativa.
AB  - A retrospective review of the microbiological and clinical data of 17 specimens
      obtained from axillary hidradenitis suppurativa (HS) over a period of 6 years was
      undertaken to study the aerobic and anaerobic microbiology of this condition. A
      total of 42 bacterial isolates (2.5 per specimen) were obtained, 12 aerobic or
      facultative (0.7 per specimen) and 30 anaerobic or micro-aerophilic (1.8 per
      specimen). Aerobic and facultative bacteria only were isolated in six (35%)
      cases, anaerobic bacteria only in seven (41%) and mixed aerobic and anaerobic
      bacteria in four (24%). The predominant aerobic bacteria were Staphylococcus
      aureus (six isolates), Streptococcus pyogenes (three) and Pseudomonas aeruginosa
      (two). The most frequently isolated anaerobes were Peptostreptococcus spp. (10),
      Prevotella spp. (seven), micro-aerophilic streptococci (four), Fusobacterium spp.
      (three) and Bacteroides spp. sensu stricto (three). This study highlights the
      polymicrobial nature and predominance of anaerobic bacteria in axillary HS and
      the need for antimicrobial thereby to reflect this.

PMID- 9920134
TI  - Usefulness of staphylococcal serology.

PMID- 9920135
TI  - Foot infection with Prevotella bivia, P. oralis and P. loescheii after wound
      licking.

PMID- 9920136
TI  - Relationships between apolipoprotein(a) phenotype and increase of lipoprotein(a)
      by troglitazone.
AB  - Troglitazone is a new oral hypoglycemic agent that reduces insulin resistance in
      non-insulin-dependent diabetes mellitus (NIDDM). However, this agent increases
      serum lipoprotein(a) [Lp(a)], which is known as an atherogenic lipoprotein. The
      relationships between the response of Lp(a) to troglitazone and the
      apolipoprotein(a) [apo(a)] phenotype were investigated in this study. Nineteen
      NIDDM patients were treated with troglitazone for 4 weeks. Lp(a) increased
      significantly from 20.1+/-16.5 mg/dL to 44.1+/-31.9 mg/dL (P<.001) in all study
      patients. Lp(a) increased from 25.7+/-34.2 mg/dL to 50.1+/-38.7 mg/dL (P = .03)
      in patients with smaller apo(a) phenotypes (S1S4 to S2S4). Lp(a) also increased
      from 17.5+/-12.0 mg/dL to 41.3+/-29.6 mg/dL (P<.01) in patients with larger
      apo(a) phenotypes (S3 to S4). Therefore, the increase of Lp(a) by troglitazone
      may be independent of the apo(a) phenotype.

PMID- 9920137
TI  - Insulin secretion and biosynthesis by the perfused pancreas of spontaneously
      hypertensive rats.
AB  - Insulin secretory activity was compared in the spontaneously hypertensive rat
      (SHR) versus the normotensive Wistar-Kyoto (WKY) rat and Wistar rat. When the
      isolated pancreas was perfused with 16.7 mmol/L glucose, insulin release was
      significantly greater in the SHR versus the other groups. On the other hand,
      there was no difference in arginine (19 mmol/L)-induced insulin secretion among
      the three groups. To determine insulin biosynthesis during glucose stimulation,
      the pancreas was perfused with 16.7 mmol/L glucose for 180 minutes. Insulin
      secretion was greater in SHR versus WKY and Wistar rats, but the net increase in
      insulin content was not different between the three groups. These results
      strongly suggest that in vivo hyperinsulinemia in the SHR is associated with
      increased in vitro insulin secretion in response to glucose. The mechanisms by
      which enhanced glucose-induced insulin secretion is linked to hypertension in the
      SHR remain unclear.

PMID- 9920138
TI  - Carbohydrate and lipid metabolism during various growth hormone dosing regimens
      in girls with Turner syndrome. Dutch Working Group on Growth Hormone.
AB  - To analyze the effects of supraphysiological dosages of growth hormone (GH) on
      carbohydrate (CH) and lipid metabolism, we investigated 87 girls with Turner
      syndrome (TS) in two studies: (1) a 4-year GH dose-response (DR) study comparing
      three groups with stepwise GH dosage increases up to 8 IU/m2/d in girls aged 2 to
      11 years, and (2) a 2-year GH administration frequency-response (FR) study in
      girls aged 11 to 17 years, comparing once-daily (OD) and twice-daily (BID)
      injections of a total GH dose of 6 IU/m2/d in combination with low-dose ethinyl
      estradiol (50 ng/kg/d orally). At baseline, impaired glucose tolerance (IGT) was
      present in 6% of the girls, and at the end of the studies, in 5%. In the DR
      study, the area under the curve for time-concentration (AUCab) for glucose after
      an oral glucose tolerance test (OGTT) showed no change over time and no
      significant difference between any of the study groups. However, in all three DR
      groups, the AUCab for insulin, fasting glucose, the insulinogenic index,
      hemoglobin A1c (HbA1c), and urinary C-peptide (uCp) were all significantly higher
      after 4 years compared with pretreatment (P<.05). In the FR study, group
      differences were not observed. Compared with healthy Dutch control subjects, the
      median baseline levels in relatively young girls in the DR study were similar for
      total cholesterol (TC) and lower for high-density lipoprotein (HDL) cholesterol.
      In contrast, the median TC levels of relatively older girls in the FR study were
      higher and HDL levels were similar. With increasing GH dosage in the DR study,
      median TC and low-density lipoprotein (LDL) levels decreased, whereas median HDL
      levels increased. The changes after 4 years were significant, including a
      decrease in the atherogenic index. GH treatment at the supraphysiological dosages
      used in this study did not increase the frequency of IGT or clinical diabetes.
      However, we observed an increased insulinogenic index indicative of insulin
      resistance. Therefore, long-term follow-up study is warranted in these otherwise
      healthy subjects. OD injection regimens changed the lipid profile toward a more
      cardioprotective direction with a significant reduction of the TC/HDL cholesterol
      ratio.

PMID- 9920139
TI  - Effect of exercise training on long-term weight maintenance in weight-reduced
      men.
AB  - This study investigated whether endurance training is effective for successful
      long-term weight maintenance after weight reduction. Fifteen male obese subjects
      (age, 37.3+/-5.2 years; body weight [BW], 96.2+/-13.6 kg; body mass index [BMI],
      30.9+/-2.8 kg x m(-2)) participated in a 16-month exercise-intervention study.
      During the first 4 months, all subjects trained three to four times weekly,
      consuming a very-low-energy diet (VLED) during the first 2 months. After the 4
      month treatment period, seven subjects continued training for 12 months (3 to 4
      times per week). The other eight subjects served as a control group not involved
      in a training program. The regain (increase during the intervention period as a
      percentage of the 4-month treatment) of BW at 16 months was 64% (+/-26%) for the
      whole group (trained v. control, 52%+/-28% v. 74%+/-20%, P = .09). The increase
      in absolute fat mass (FM) was significantly lower at 16 months for the trained
      group (trained v. control, 4.8+/-1.9 v. 9.0+/-3.3 kg), as was the regain of FM at
      16 months (trained v. control, 61%+/-24% v. 92%+/-32%, P = .05). The amount of
      regain of the waist circumference, waist to hip ratio (WHR), and sagittal
      diameter were correlated with the amount of training (hours) performed weekly
      (deltawaist, r = -.55, P<.05; deltaWHR, r = -.50, P = .06; deltasagittal
      diameter, r = -.53, P<.05). Physical fitness parameters (maximal power output
      [Wmax] and oxygen uptake [Vo2 max]) were significantly increased in both groups
      at 4 months. Trained subjects maintained high levels of physical fitness at 16
      months, in contrast to the control group. In conclusion, although BW regain was
      not significantly different between the groups, trained subjects showed less
      regain of FM and higher levels of physical fitness, factors related to a lower
      risk for cardiovascular disease (CVD), compared with the control group.
      Furthermore, the regain of FM, which occurred even in the exercising group with a
      relatively intensive training program, suggests that maintenance of fat loss is
      extremely difficult.

PMID- 9920141
TI  - Diabetes mellitus: polymorphonuclear leukocyte (PMN) filtration parameters and
      PMN membrane fluidity after chemotactic activation.
AB  - The goal of this research was to determine leukocyte rheology at baseline and
      after chemotactic activation in type I and type II diabetics. In 19 normal
      subjects, 21 type I diabetics, and 16 type II diabetics at baseline and after in
      vitro chemotactic activation (prolonged for 5 and 15 minutes) with two
      stimulating agents (4-phorbol 12-myristate 13-acetate [PMA] and N-formyl
      methionyl-leucyl-phenylalanine [fMLP]), we evaluated polymorphonuclear (PMN)
      filtration parameters (using a St. George filtrometer [Carri-Med, Dorking, UK]
      and considering the initial relative flow rate [IRFR] and the concentration of
      clogging particles [CP]) and PMN membrane fluidity (obtained by marking PMNs with
      the fluorescent probe 1-(4-[trimethylamino]phenyl)-6-phenyl-1,3,5-hexatriene (TMA
      DPH). At baseline, there was a difference between normals and type I and II
      diabetics for PMN membrane fluidity only. After activation in normals and
      diabetics of both types, a significant variation was present in PMN filtration
      parameters (IRFR and CP) at both 5 and 15 minutes. In normals, no variation was
      present in PMN membrane fluidity after activation with PMA or fMLP. After PMN
      activation, only in type I diabetics was a significant decrease in PMN membrane
      fluidity present at both 5 and 15 minutes. After PMN activation with either PMA
      or fMLP in comparison to basal values, only the mean variation (delta%) of the
      IRFR was significantly different between normals, type I diabetics, and type II
      diabetics at both 5 and 15 minutes. From the data obtained, it is evident that
      after activation, the PMN filtration pattern shows a specific behavior in
      diabetics of both types, while PMN membrane fluidity changes only in type I
      diabetics. The latter finding may be the basis of a metabolic pattern present in
      PMNs of this type, revealed after in vitro activation.

PMID- 9920140
TI  - Differential effects of cis and trans fatty acids on insulin release from
      isolated mouse islets.
AB  - In vitro and in vivo studies in animals have shown that elevated levels of free
      fatty acids (FFAs) induce impaired beta-cell function corresponding to the
      abnormalities observed in non-insulin-dependent diabetes mellitus (NIDDM).
      Previously, it was demonstrated that the chain length and degree of unsaturation
      are of importance for the insulinotropic effect of fatty acids. However, it is
      not known if the spatial configuration of the fatty acid influences beta-cell
      function. The present study examines whether cis and trans fatty acids acutely
      influence insulin release and glucose oxidation in isolated mouse islets in the
      same way and to the same extent. Thus, we studied the impact of both cis and
      trans forms of C 18:1 fatty acids. We found that cis and trans vaccenic acid (cis
      and trans C 18:1 delta11), as well as oleic acid (cis C 18:1 delta9) and elaidic
      acid (trans 18:1 delta9), caused a dose-dependent increase in glucose (16.7
      mmol/L)-stimulated insulin secretion during static islet incubations. The maximal
      stimulatory effect for cis and trans vaccenic acid and for oleic and elaidic acid
      was observed at concentrations of 2.0 and 3.0 mmol/L, respectively. The trans
      isomers, trans vaccenic and elaidic acid, elicited a higher maximal insulin
      output than the respective cis isomers, cis vaccenic and oleic acid. In the
      presence of another insulin secretagogue, L-leucine, trans vaccenic but not
      elaidic acid caused a higher response than their cis isomeric fatty acids. The
      higher potency of trans fatty acids compared with the cis forms was confirmed in
      perifusion experiments. Both cis and trans C 18:1 fatty acids stimulated insulin
      secretion in a glucose-dependent manner. Also, glucose oxidation was influenced
      differentially by the isomers of fatty acids. Glucose oxidation at 16.7 mmol/L
      glucose was significantly inhibited by oleic and cis vaccenic acid compared with
      elaidic and trans vaccenic acid, respectively. In summary, our results
      demonstrate that the fatty acid spatial configuration modulates glucose oxidation
      and insulin secretion in mouse beta cells.

PMID- 9920142
TI  - BM 17.0744: a structurally new antidiabetic compound with insulin-sensitizing and
      lipid-lowering activity.
AB  - BM 17.0744 (2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid) is a substance from
      a group of omega-substituted alkyl carboxylic acids with the general formula,
      ring-spacer-carboxylic acid. With BM 17.0744-a compound structurally unrelated to
      thiazolidinediones--antihyperglycemic and antihyperinsulinemic potency has been
      demonstrated in various animal models of type II diabetes. The antidiabetic
      effect is independent of the genetic background of the disease, gender, and
      animal species. The 24-hour blood glucose profile was dose- and time-dependently
      improved in ob/ob mice after a single and fourth oral administration of 0.3, 1,
      and 3 mg/kg/d. A dose-dependent reduction of hyperglycemia (10%, 15%, 28%, and
      66%) was found in db/db mice after the fifth oral administration of 3, 10, 30,
      and 100 mg/kg/d. Hyperinsulinemia was reduced dose-dependently in yellow KK mice
      by 1%, 24%, 34%, and 66% after the fifth oral administration of 0.3, 1, 3, and 10
      mg/kg/d. Overall glucose metabolism was predominantly higher in euglycemic
      hyperinsulinemic clamp studies in obese fa/fa rats pretreated for 14 days with 10
      mg/kg/d BM 17.0744. The data in diabetic and insulin-resistant animals suggest an
      improvement of insulin action that is supported by enhancement of insulin effects
      in vitro. There is no evidence of a risk for hypoglycemia in diabetic and
      metabolically healthy animals. Triglyceride (TG) and cholesterol were reduced in
      the serum of metabolically healthy rats, as well as serum lipids in db/db mice,
      which suggests this effect is independent of amelioration of the diabetic status.
      Lipid-lowering effects in diabetic and healthy animals show an additional
      property of BM 17.0744. Because of its antidiabetic and lipid-lowering potency,
      the substance is of great interest in treating the metabolic syndrome. Lipid
      decreases in rats are associated with a dose-dependent increase in carnitine
      acetyltransferase activity in the liver to about 100-fold (12.5 mg/kg/d). This
      together with hepatomegaly in small rodents may indicate peroxisomal
      proliferation, a phenomenon considered species-specific. Its relevance for humans
      is well documented for other classes of compounds including fibrates. Specific
      side effects of insulin sensitizers of the thiazolidinedione type, such as an
      increase in body weight and heart weight, could not be observed after 4-week oral
      application of BM 17.0744 in rats. In general, BM 17.0744 was well tolerated in
      the pharmacological dose range in all species tested.

PMID- 9920143
TI  - Immunoblockade of endogenous glucagon-like peptide-1 by monoclonal antibodies in
      conscious rats: effect on the insulin response to intragastric glucose.
AB  - The physiological action of endogenous active forms of glucagon-like peptide-1
      (GLP-1) on the insulin response to intragastric glucose was studied in conscious
      male Wistar rats by immunoblockade with two monoclonal antibodies directed
      against different epitopes of GLP-1(7-36)amide. Plasma concentrations of
      intraperitoneally injected monoclonal antibodies were determined before and
      during each experiment by an enzyme-linked immunosorbent assay (ELISA) specific
      for GLP-1-binding antibodies. Three hours after injection of the two monoclonal
      antibodies, the plasma insulin response (area under the curve) following
      intragastric glucose 1 g/kg was reduced to a mean level (mean +/- SEM) of 60%+/
      8% (n = 11) of control responses previously determined in the same rats, and the
      time course of the response showed almost no increase in insulin during the first
      10 minutes, reaching a maximum of 45.1+/-4.6 microU/mL at 30 minutes, in contrast
      to the rapid increase of the control response to a maximum of 64.5+/-5.1
      microU/mL at 15 minutes. Total C-terminally amidated GLP-1 measured by
      radioimmunoassay (RIA) of acid ethanol-extracted plasma increased from a mean
      basal level of 10+/-2 pmol/Lto a peak of 31+/-5 pmol/L at 15 minutes in the
      control experiments, while basal and response levels greater than 100 pmol/L were
      recorded after antibody treatment. The increase of plasma glucose was reduced in
      the presence of the antibodies, peaking at a mean of 9.7+/-0.3 mmol/L at 30
      minutes, compared with 11.8+/-0.5 mmol/L at 30 minutes in the control
      experiments. The action of GLP-1 appears particularly important for the early
      insulin response to ingested glucose, and the unexpected effect of the antibodies
      on the glucose response may point to a net promoting effect of GLP-1 on
      intestinal glucose absorption.

PMID- 9920144
TI  - Randomized crossover study of gemfibrozil versus lovastatin in familial combined
      hyperlipidemia: additive effects of combination treatment on lipid regulation.
AB  - The most appropriate therapy for combined hyperlipidemia remains to be
      determined. We compared the lipid-regulating effects of gemfibrozil and
      lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a
      randomized, double-blind, placebo-controlled crossover study including 8-week
      courses of one drug followed by a washout period and a crossover phase to the
      alternate drug. After completion of the trial, open-label combination therapy was
      given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in
      the reduction of total cholesterol (23% v. 9%, P<.001) and low-density
      lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed
      lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low
      density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of
      high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin
      caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than
      gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug
      induced changes in lipoprotein composition indicated that gemfibrozil reduced
      both the number and size of VLDL particles and lovastatin decreased the number of
      LDL particles. Combined treatment was safe and had additive effects on lipids,
      causing significant (P<.001) reductions in total cholesterol (32%), triglycerides
      (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol
      (19%). Target LDL cholesterol levels were achieved only in 11% of patients given
      gemfibrozil alone and triglycerides decreased to target levels in 22% after
      lovastatin alone, whereas combined therapy normalized both lipid fractions in 96%
      of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels
      but favorably influences the putative atherogenic alterations of lipoprotein
      composition that are related to hypertriglyceridemia. Conversely, lovastatin
      markedly decreases LDL cholesterol but has little effect on triglyceride-rich
      lipoproteins. Combination treatment safely corrects all of the lipid
      abnormalities in most patients.

PMID- 9920145
TI  - Stiffness of the aortic wall in hypercholesterolemic children.
AB  - Arterial stiffness may be an indicator of early vascular changes signaling the
      development of vascular disease, while hypercholesterolemia is a well-recognized
      promoter of atherogenesis. It has been shown that hypercholesterolemic children
      have a thicker intima-media in the carotid artery than children with normal
      cholesterol. The aim of this study was to assess the stiffness of the abdominal
      aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of
      the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and
      without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively).
      Ultrasound imaging of the abdominal aorta that allowed diameter measurements was
      available in 67 children. Using an image-processing workstation, the maximum and
      minimum internal diameter of the aorta was measured, and the following indices of
      elastic properties of the abdominal aorta were derived: arterial strain, pressure
      strain elastic modulus, and stiffness. No statistical difference for aortic
      strain, stiffness, and elastic modulus was found in normocholesterolemic compared
      with hypercholesterolemic children. The effect of age on the elastic modulus was
      different in the two groups: in normal children, the elastic modulus increased
      linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high
      cholesterol group had a weak increase in this parameter with age (y =
      0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic
      modulus vage) was significantly different in the two groups (t = 2.45, P = .017).
      The behavior of arterial stiffness with respect to age was similar, y =
      0.677+0.018 x age (P = .002) in normocholesterolemic children and y =
      2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the
      regression equations (stiffness v. age) was significantly different in the two
      groups (t = 2.37, P = .021). The present study demonstrates an influence of
      hypercholesterolemia on age-related modification in the elastic properties of the
      aorta. A remodeling of the aortic wall in hypercholesterolemic children
      (cholesterolemia >247 mg/dL) could explain the different age-dependent increase
      in aortic elastic modulus and stiffness.

PMID- 9920146
TI  - Interrelationships between postprandial lipoprotein B:CIII particle changes and
      high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.
AB  - We studied the relationships postprandially between triglyceride-rich lipoprotein
      (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL)
      and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial
      triglyceridemia response observed in MHL but not HCL patients was essentially
      dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response
      was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL
      compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity
      was postprandially enhanced only in MHL patients, and this elevation persisted in
      the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of
      VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients
      was also characterized by high levels of apolipoprotein B (apoB)-containing
      lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased
      levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01),
      reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL
      compared with HCL patients, decreased HDL2 levels were related to both HDL2b and
      HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased
      apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I
      only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%,
      respectively, P<.01 for both). The significant inverse correlations between the
      postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL
      patients underline the close TRL-HDL interrelationships. Our findings indicate
      that TRL and HDL abnormalities evidenced at fasting were postprandially
      amplified, tightly interrelated, and persistent during the late fed period in
      mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially
      originated and may constitute proatherogenic lipoprotein disorders additional to
      the HCL in MHL patients.

PMID- 9920147
TI  - Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on sterol
      absorption in hypercholesterolemic subjects.
AB  - To investigate the potential effects of high-dose 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor on plasma phytosterol, total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
      cholesterol (HDL-C), and triglyceride (TG), hypercholesterolemic subjects
      received 40 or 80 mg/d simvastatin in a 24-week prospective clinical trial.
      Plasma lipid levels were analyzed enzymatically, and plasma phytosterol
      concentrations were determined using gas-liquid chromatography. The change in the
      plasma phytosterol-campesterol level was used as an indicator of cholesterol
      absorption in humans. Simvastatin treatment reduced plasma campesterol (-24%, P =
      .017) but did not affect circulating stigmasterol and sitosterol levels. A dose
      of 80 mg/d simvastatin produced a larger decrease (P = .050) in plasma
      campesterol (0.1680 mmol/L) than 40 mg/d (0.0237 mmol/L) versus baseline. There
      was a positive correlation between plasma campesterol and TC both before (r =
      .54, P = .027) and after (r = .63, P = .009) treatment. Plasma TC and TG levels
      did not differ between groups receiving 40 or 80 mg/d simvastatin. Simvastatin
      treatment reduced circulating TC, LDL-C, and TG by 40%, 50%, and 33% (P<.007),
      respectively. There was no significant effect of simvastatin on plasma HDL-C, but
      the HDL-C/LDL-C ratio increased 1.3-fold (P<.0001). In conclusion, this HMG-CoA
      reductase inhibitor reduces the plasma campesterol level, a marker of cholesterol
      absorption, which may contribute to the mechanism by which simvastatin decreases
      circulating cholesterol levels.

PMID- 9920148
TI  - Effect of long-term valproic acid administration on the efficiency of carnitine
      reabsorption in humans.
AB  - To elucidate the etiology of valproic acid-induced carnitine deficiency, we
      tested the hypothesis that long-term valproic acid administration decreases the
      rate of carnitine reabsorption. Thirteen healthy men participated in a 34-day
      protocol in which carnitine clearance was measured before and after 28 days of
      valproic acid administration. During valproic acid administration (days 6 to 33),
      plasma free and total carnitine concentrations decreased (18% and 12%,
      respectively, P<.05) by 16 days, but returned to pretreatment concentrations by
      28 days. From day 14 to day 30, the rate of free carnitine excretion was 50%
      lower than at baseline (day 4, P<.05). Free and total carnitine clearance,
      indexed to the glomerular filtration rate, was lower after valproic acid
      administration (P<.01). Contrary to our hypothesis, after 28 days of valproic
      acid administration, the rate of carnitine reabsorption was enhanced independent
      of the glomerular filtration rate and filtered load. Changes in the plasma
      concentration, rate of excretion, and clearance were specific for carnitine and
      were not generalized in magnitude or direction to the other amino acids. We
      conclude that the kidney adapts to conserve carnitine during valproic acid
      administration and therefore does not cause valproic acid-induced carnitine
      depletion in adults.

PMID- 9920149
TI  - Peripheral tissue glucose uptake is not reduced after an oral glucose load in
      Southern Italian subjects at risk of developing non-insulin-dependent diabetes
      mellitus.
AB  - Studies searching for the inherited defects that cause non-insulin-dependent
      diabetes mellitus (NIDDM) have been performed mostly in Northern European
      subjects using the hyperinsulinemic clamp technique. The conclusion drawn from
      most of these studies is that peripheral insulin resistance is likely a primary
      inherited defect. Our aim was to examine early defects in glucose metabolism
      using a more physiological technique in a different ethnic group. For this, a
      double-label oral glucose tolerance test (OGTT) was performed in young diabetes
      prone Southern Italian subjects who had both parents with NIDDM (relatives) and
      in subjects with no family history of NIDDM (matched for age, weight, and
      ethnicity). Fasting plasma glucose and insulin in the relatives were normal;
      however, they had impaired glucose tolerance during the OGTT. This was due to
      reduced hepatic glucose uptake (17.9+/-2.8 v. 28.1+/-2.3 g, P<.02). No defects
      were found in the metabolic clearance rate (MCR) of glucose or endogenous glucose
      production. During an intravenous glucose tolerance test (IVGTT), insulin
      sensitivity was again found to be normal (3.04+/-0.65 in relatives v. 2.33+/-0.38
      min(-1) per micromol x L(-1) x min in controls), with a marked reduction in first
      phase insulin secretion in the relatives (110+/-12 v. 211+/-18 pmol x L(-1) x min
      per mmol x L(-1), P<.001). A strong correlation was found between hepatic glucose
      uptake and insulin secretion (r = .81, P<.001), which may suggest that the same
      abnormality operates in both the liver and pancreas. Therefore, the metabolic
      defect that causes hyperglycemia in diabetes-prone subjects is not always a
      reduced peripheral insulin sensitivity. The genetic basis of NIDDM may differ
      between different ethnic groups.

PMID- 9920150
TI  - Vitamin E status in patients with liver cirrhosis: normal or deficient?
AB  - The study aim was to compare the ratio of vitamin E to serum cholesterol with the
      serum vitamin E level alone as a measure of vitamin E status in patients with
      different degrees of liver dysfunction. Assessment of serum vitamin E and total
      serum cholesterol was performed in 85 patients with liver cirrhosis at Child's
      stage A (n = 26), B (n = 26), and C (n = 33) and 50 patients with noncirrhotic
      liver disease. As surrogate markers of liver function, 7alpha-hydroxycholesterol
      and prealbumin concentrations and the plasma prothrombin time were determined.
      Mean serum vitamin E concentrations in Child A, B, and C patients were 27.4%,
      36.9%, and 37.3% lower, respectively, than in healthy controls (P<.01). Twelve of
      26 Child A, 14 of 26 Child B, and 14 of 33 Child C patients had vitamin E
      deficiency with respect to the absolute values, i.e., serum levels less than
      13.76 micromol/L (5% percentile of healthy controls). In contrast, only two of 26
      Child A, five of 26 Child B, and five of 33 Child C patients (P<.01 for Child A/B
      and P<.05 for Child C) were vitamin E-deficient according to the serum vitamin E
      to cholesterol ratio, i.e., less than 2.86 micromol/mmol. Serum vitamin E was
      correlated significantly with prealbumin, 7alpha-hydroxycholesterol, and the
      plasma prothrombin time, but the vitamin E to cholesterol ratio was not.
      Correcting serum vitamin E for total serum cholesterol in patients with liver
      cirrhosis leads to the phenomenon of reduced serum vitamin E levels inadvertently
      shifted toward normal values. In patients with liver cirrhosis, the absolute
      vitamin E concentration correlates better with the typical clinical and
      biochemical findings of the disease than the vitamin E to cholesterol ratio.
      Therefore, a considerable number of patients with advanced liver cirrhosis might
      actually be vitamin E-deficient.

PMID- 9920151
TI  - Regression and progression of cardiac sympathetic dysinnervation complicating
      diabetes: an assessment by C-11 hydroxyephedrine and positron emission
      tomography.
AB  - Cardiovascular denervation complicating diabetes has been implicated in sudden
      cardiac death potentially by altering myocardial electrical stability and
      impairing myocardial blood flow. Scintigraphic evaluation of cardiac sympathetic
      integrity has frequently demonstrated deficits in distal left ventricular (LV)
      sympathetic innervation in asymptomatic diabetic subjects without abnormalities
      on cardiovascular reflex testing. However, the clinical significance and
      subsequent fate of these small regional defects is unknown. This study reports
      the results of a prospective observational study in which positron emission
      tomography (PET) with (-)-[11C]-meta-hydroxyephedrine ([11C]-HED) was used to
      evaluate the effects of glycemic control on the progression of small regional LV
      [11C]-HED retention deficits in 11 insulin-dependent diabetic subjects over a
      period of 3 years. The subjects were divided into two groups based on attained
      glycemic control during this period: group A contained six subjects with good
      glycemic control (individual mean HbA1c <8%), and group B contained five subjects
      with poor glycemic control (individual mean HbAlc > or =8%). Changes in regional
      [11C]-HED retention were compared with reference values obtained from 10 healthy
      aged-matched nondiabetic subjects. At baseline, abnormalities of [11C]-HED
      retention affected 7.3%+/-1.4% and 9.9%+/-6.6% of the LV in group A and B
      subjects, respectively, with maximal deficits of LV [ C]-HED retention involving
      the distal myocardial segments. At the final assessment in group A, the extent of
      the deficits in [11C]-HED retention decreased to involve only 1.7%+/-0.7% of LV
      (P<.05 v. baseline scan), with significant increases in [11C]-HED retention
      occurring in both the distal and proximal myocardial segments. In contrast, in
      group B with poor glycemic control, the extent of [11C]-HED deficits increased to
      involve 34%+/-3.5% of the LV (P<.01 v. baseline), with retention of [11C]-HED
      significantly decreasing in the distal segments ([11C]-HED retention index,
      0.066+/-0.003 v. 0.057+/-0.002, P<.05, at baseline and final assessment,
      respectively). Poor glycemic control was associated with increased heterogeneity
      of LV [11C]-HED retention, since three of five group B subjects developed
      abnormally increased [11C]-HED retention in the proximal myocardial segments. In
      conclusion, defects in LV sympathetic innervation can regress or progress in
      diabetic subjects achieving good or poor glycemic control, respectively. In
      diabetic subjects with early cardiovascular denervation, institution of good
      glycemic control may prevent the development of myocardial sympathetic
      dysinnervation and enhanced cardiac risk.

PMID- 9920152
TI  - Effects of starvation and diabetes on the metabolism of [2,3-13C]succinic acid
      dimethyl ester in rat hepatocytes.
AB  - The metabolism of [2,3-13C]succinic acid dimethyl ester ([2,3-13C]-SAD) 10 mmol/L
      was examined in hepatocytes from overnight-fasted normal rats, 3-day starved
      rats, and overnight-fasted hereditarily diabetic Goto-Kakizaki (GK) rats. The
      amount of 13C-labeled succinate, fumarate, malate, lactate, alanine, and
      aspartate released by the hepatocytes was much higher in fasted normal rats than
      in starved or diabetic animals. Although the integrated areas of the 13C2 and
      13C3 signals assigned to double-labeled malate, lactate, or alanine were not
      significantly different, the amount of single-labeled malate, lactate, alanine,
      and aspartate was higher in C3- versus C2-labeled isotopomers. The release of 13C
      labeled glucose by the hepatocytes was lower in fasted versus starved or diabetic
      rats. Virtually all hexose molecules double-labeled in the C1-C2-C3 and/or C6-C5
      C4 moieties corresponded to the [1,2-13C] and/or [5,6-13C] isotopomers. However,
      in the case of the single-labeled species, 13C-labeling of C1 (or C6) exceeded
      that of C2 (or C5). Both the single- and double-labeled molecules enriched with
      13C in the C1-C2-C3 moiety were less abundant than those labeled in the C6-C5-C4
      moiety, with such asymmetry being most marked in overnight-fasted normal rats,
      less pronounced in diabetic animals, and virtually absent in starved rats. These
      findings document that SAD is efficiently metabolized in hepatocytes, with its
      use as a gluconeogenic precursor being influenced by the nutritional and hormonal
      status of the animals. The present experiments also reinforce the view that
      asymmetrical labeling of glucose by 13C-labeled precursors is modulated by the
      relative contribution of exogenous and endogenous nutrients to the production of
      triose phosphates incorporated into the hexose.

PMID- 9920153
TI  - Hyperinsulinism and sex hormones in young adult African Americans.
AB  - Hyperinsulinemia is a risk factor for cardiovascular disease, and is linked with
      non-insulin-dependent diabetes mellitus (NIDDM), hyperlipidemia, obesity, and
      hypertension. Sex hormones also play a role in the metabolic alterations
      associated with the risk for cardiovascular disease. A reduction in sex hormone
      binding globulin (SHBG) may be predictive of future NIDDM particularly in women.
      The postmenopausal decline in estrogen is also associated with an increase in
      risk factor expression in women. Since African Americans experience a greater
      prevalence of NIDDM, obesity, and hypertension, conditions associated with
      hyperinsulinemia, the purpose of this study was to determine if alterations in
      sex hormone levels are associated with the plasma insulin concentration in young
      adult African Americans, and to determine if there are sex differences in the
      effect of insulin on lipids and sex hormones. In a sample of 221 nondiabetic
      African American men (n = 105) and women (n = 116) with a mean age of 31 years,
      we examined the relationship of the plasma insulin concentration with the body
      mass index (BMI), blood pressure, plasma lipids, and sex hormones, including free
      testosterone, estradiol, and SHBG. Plasma insulin increased with the BMI and
      other measures of adiposity (P<.001) in men and women. Significant correlations
      of insulin with plasma lipids were also present in both sexes. There was a
      significant inverse correlation of insulin with SHBG in both men (r = .28, P =
      .007) and women (r = .27, P = .02). There was a significant direct correlation of
      insulin with free testosterone in women (r = .032, P<.001). Stepwise multiple
      regression analyses with insulin as the dependent variable detected the BMI,
      triglyceride, and apolipoprotein A1 as significant contributors to the plasma
      insulin concentration in men. In women, the multiple regression model detected
      percent body fat, low-density lipoprotein (LDL) cholesterol, and free
      testosterone as significant contributors to plasma insulin. These data on young
      African Americans demonstrate a significant relationship between hyperinsulinemia
      and obesity, atherogenic lipid status, and lower SHBG. In the premenopausal
      women, the lower SHBG is linked with higher free testosterone, favoring a
      condition of relative androgen excess.

PMID- 9920154
TI  - Elevated serum semicarbazide-sensitive amine oxidase activity in non-insulin
      dependent diabetes mellitus: correlation with body mass index and serum
      triglyceride.
AB  - Previous clinical studies reported elevated semicarbazide-sensitive amine oxidase
      (SSAO) activity in insulin-dependent diabetes mellitus (IDDM), but there are not
      sufficient data about SSAO in non-insulin-dependent diabetes mellitus (NIDDM).
      The present study was conducted to investigate serum SSAO activity in NIDDM
      patients compared with nondiabetic and IDDM patients. Serum SSAO activity in 61
      patients with diabetes (n = 34 NIDDM and n = 27 IDDM) and 36 controls was
      determined using 14C-benzylamine as a substrate. NIDDM and IDDM patients
      exhibited higher SSAO activity compared with controls ([mean +/- SD] NIDDM,
      164.60+/-69.43 pmol/mg protein/h, P<.0001; IDDM, 143.91+/-72.45 pmol/mg
      protein/h, P<.002; control, 91.46+/-28.11 pmol/mg protein/h). There was a
      significant positive correlation between serum SSAO activity and the body mass
      index (BMI), body weight, hemoglobin A1c (HbA1c), fasting plasma glucose, and
      triglycerides. Within the control group, SSAO correlated with total cholesterol
      levels. The progression and severity of diabetic complications such as angiopathy
      may be exacerbated by cytotoxic metabolites (e.g., formaldehyde and hydrogen
      peroxide) formed by SSAO. These results reveal the possibility that elevated
      serum SSAO activity in association with obesity and hyperlipidemia may be a
      cardiovascular risk factor in diabetes mellitus.

PMID- 9920155
TI  - Association between low-density lipoprotein composition and its metabolism in non
      insulin-dependent diabetes mellitus.
AB  - Atheroma is related to low-density lipoprotein (LDL) composition. LDL in diabetic
      patients-a group with increased risk of severe atheroma-has been shown by our
      group and others to have various compositional alterations that are potentially
      atherogenic. Little is known about the relationship between LDL turnover and
      composition. This study examined the relationship between LDL composition and
      turnover in non-insulin-dependent diabetes mellitus (NIDDM) patients. Twenty-two
      NIDDM patients with a mean plasma cholesterol of 6.6+/-1.5 mmol/L were studied.
      Twelve subjects were hypercholesterolemic (mean cholesterol, 7.7+/-0.8 mmol/L),
      and eight of these agreed to be studied a second time after 4 weeks of treatment
      with simvastatin. LDL was isolated by density gradient ultracentrifugation,
      iodinated, and reinjected into the patient. LDL turnover was determined by
      measuring the clearance of [125I]-LDL from plasma over a 10-day period. The LDL
      residence time, determined using a biexponential model, correlated negatively
      with the body mass index (BMI) (r = -.73, P<.001) and serum triglycerides (r = -
      .57, P<.01). There was a significant inverse correlation between LDL residence
      time and the LDL esterified to free cholesterol ratio in hypercholesterolemic
      subjects (r = -.94, P<.001). There was a significant inverse relationship between
      LDL residence time and both hemoglobin A1c (HbA1c) and fasting blood glucose in
      these subjects before treatment (P<.005). After simvastatin therapy, the
      relationships were no longer significant. Simvastatin treatment was associated
      with a shorter LDL residence time (P<.01) and a decrease in LDL glycation
      (P<.001) with virtually no change in diabetic control (HbA1c, 6.0%+/-3.1% v.
      6.3%+/-3.3%, NS). This study suggests that a decrease in residence time by
      upregulation of the LDL receptor with simvastatin alters LDL composition in a way
      that is likely to render the particle less atherogenic.

PMID- 9920156
TI  - Troglitazone and vascular reactivity: role of glucose and calcium.
AB  - We sought to determine whether insulin/insulin-like growth factor-1 (IGF-1) and
      an insulin-sensitizing agent, troglitazone, have additive vasodilatory effects
      and the possible involvement of intracellular Ca2+ ([Ca2+]i) and/or glucose
      utilization in these effects. Contractile responses to norepinephrine (NE) and
      potassium chloride (KCl), as well as relaxation to endothelium-dependent
      (acetylcholine [Ach]) and -independent (sodium nitroprusside [NaNP]) agents, were
      examined in rat tail artery rings in the presence of insulin/IGF-1 and/or
      troglitazone. Endothelium-intact tail artery rings stretched to 1 g tension were
      preincubated with troglitazone (3 micromol/L) and/or insulin/IGF-1 (100 nmol/L)
      prior to addition of graded doses of NE and KCI. A 90-minute exposure to
      troglitazone attenuated the maximal contraction to graded doses of NE and KCI
      (P<.0001). Incubation in glucose-free medium decreased the responses only to NE;
      troglitazone further attenuated the NE-induced contraction (P = .001). In
      submaximally precontracted endothelium-intact rings, troglitazone increased the
      relaxation both to NaNP (P<.0001) and to Ach (P = .001). Contraction experiments
      in depolarizing KCI (25 mmol/L) or Ca2+ -free buffer showed that troglitazone and
      insulin have a similar Ca2+ dependency. In conclusion, troglitazone, like
      insulin/IGF-1, attenuates responses to vasoactive agonists through a Ca2+ 
      dependent mechanism that may require the presence of glucose but is independent
      of insulin action and nitric oxide (NO) production.

PMID- 9920157
TI  - Lipid abnormalities in Taiwan aborigines with gout.
AB  - An epidemiologic study to determine lipids and biochemical traits was performed
      in central Taiwan aborigines with and without gout and in the local Han Chinese.
      The lipid profile included measurement of serum triglyceride, cholesterol, high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C), apolipoprotein A-I (apoA-I), and apoB. The results showed no significant
      difference for body mass index (BMI) and cholesterol between the three groups.
      Greater alcohol consumption was found in aborigines with gout compared with the
      other two groups. With univariate analysis, serum triglyceride, uric acid,
      creatinine, LDL-C, and apoB were significantly higher in aborigines with gout
      versus aborigines without gout or Han people (P<.001). By contrast, HDL-C and
      apoA-I were significantly lower in aborigines with gout (P<.001 or .01). However,
      with multivariate analysis, only serum triglyceride, uric acid, and apoB-1 were
      significantly different between aborigines with versus without gout. In
      conclusion, the apparent lipid abnormalities, particularly triglyceride and apoB,
      in Taiwan aborigines with gout are unlikely secondary to obesity. Instead,
      excessive alcohol intake or genetic factors may play a role in inducing
      hyperlipidemia in gout.

PMID- 9920158
TI  - Glucagon-like peptide-1 has no insulin-like effects in insulin-dependent diabetic
      dogs maintained normoglycemic and normoinsulinemic.
AB  - A pharmacological concentration of glucagon-like peptide-1 (GLP-1) in the insulin
      deficient state clearly decreases the blood glucose level. Therefore, this study
      was designed to evaluate a putatively relevant effect of the gastrointestinal
      peptide as an adjuvant to insulin replacement therapy. GLP-1 (GLP-1(7-36) amide
      10 pmol x kg(-1) x min(-1)) was infused intravenously over 8 hours in nine
      fasting, C-peptide-negative diabetic dogs. The animals were under normoglycemic
      control by glucose-controlled insulin infusion (GCII) during the night before and
      during GLP-1 administration. During the paired control tests, the animals
      received saline infusion instead of GLP-1. In addition to the insulin infusion
      rates required to maintain normoglycemia, hormones, metabolites, and the turnover
      rates for glucose (6-3H-glucose), alanine (U-14C-alanine), and urea (15N2-urea)
      were measured during the final 2 hours of GLP-1 administration. Circulating
      plasma GLP-1 levels increased from 3+/-1 to 17+/-7 pmol/L. There was no
      significant difference in the insulin infusion rate between the experimental and
      control groups (0.43+/-0.05 v. 0.40+/-0.05 mU x kg(-1) x h(-1), average over the
      entire interval). Glycemia was maintained at a practically identical level (4.9+/
      0.3 v. 4.8+/-0.4 mmol/L). Also, the concentration of plasma insulin-which was not
      hyperinsulinemic--and pancreatic glucagon remained unaltered. We found no
      appreciable effect of GLP-1 on glucose production and metabolic clearance,
      alanine turnover and the formation of glucose from alanine (1.8+/-0.2 v. 1.4+/
      0.2 micromol x kg(-1) x min(-1), or the urea production rate as a measure of
      overall amino acid catabolism (4.1+/-0.4 v. 4.1+/-0.4 micromol x kg(-1) x min(
      1)). Thus, no conclusive adjuvant effect of GLP-1 was ascertained in insulin
      treated diabetic dogs under normoglycemic control.

PMID- 9920159
TI  - Epitope mapping: three-dimensional insights from molecular biology.

PMID- 9920160
TI  - Detecting alloantibodies in patients with autoantibodies.

PMID- 9920161
TI  - Evaluation of methods for detecting alloantibodies underlying warm
      autoantibodies.
AB  - BACKGROUND: In pretransfusion testing of patients whose sera contain
      autoantibodies reacting optimally at 37 degrees C, it must be determined whether
      alloantibodies are also present. Two approaches, testing a 1-in-5 dilution of
      patients' sera and the adsorption of sera in the presence of polyethylene glycol
      (PEG), have been proposed as alternatives to the time-consuming approach of
      adsorbing sera with ficin- or ZZAP-treated red cells (RBCs). The three approaches
      were compared. STUDY DESIGN AND METHODS: Patients' sera containing warm
      autoantibodies, with and without alloantibodies, were retested 1) after dilution
      (1-in-5) and 2) after adsorption with allogeneic RBCs in the presence of PEG.
      Results were compared to those after adsorption with ZZAP-treated allogeneic
      RBCs. RESULTS: Dilution (1-in-5): Twenty-seven of 119 sera (7/26 [27%] with and
      20/93 [22%] without alloantibodies) did not react; one example each of alloanti
      D, -E, -e, -Fy(a), and -Jk(a), and two examples of anti-Jk(b) were not detected
      at a dilution of 1 in 5. Alloantibodies were identified in 5 (19%) of 26 1-in-5
      diluted sera containing alloantibodies; 87 (73%) of 119 sera still reacted with
      all cells and would have required further workup. PEG adsorption: Thirty-nine
      sera were tested after parallel PEG and ZZAP adsorptions. The PEG adsorptions
      required a total of 55 aliquots of adsorbing cells and 13.75 hours, whereas ZZAP
      adsorptions required 61 aliquots and 30.5 hours. All alloantibodies (anti-D [3], 
      C [2], -c [1], -E [4], -K [2], -Fy(a) [1], -Jk(a) [2], -Jk(b) [1]) reacted in the
      adsorbed serum-PEG mixtures at a strength equal to or greater than that in the
      ZZAP-adsorbed sera. CONCLUSION: Although the 1-in-5 dilution approach is
      convenient, only 22 percent of warm autoantibodies without alloantibodies were
      nonreactive, and 27 percent of alloantibodies of potential clinical significance
      were not detected. PEG adsorption appears to give similar results to those of
      ZZAP adsorption, but it has the advantages of eliminating the cost and time of
      prior treatment of the allogeneic adsorbing cells and of a reduction of at least
      a 50 percent in adsorption time.

PMID- 9920162
TI  - Site-directed mutagenesis of the human D antigen: definition of D epitopes on the
      sixth external domain of the D protein expressed on K562 cells.
AB  - BACKGROUND: The antigens of the human Rh system are of great clinical
      significance in transfusion medicine and pregnancy. Of the Rh system antigens, D
      is clinically the most important, being one of the most immunogenic structures
      arising from human cells. The human D antigen represents a collection of epitopes
      expressed on a red cell membrane protein that is predicted to have 12 membrane
      spanning segments giving rise to six exofacial domains. STUDY DESIGN AND METHODS:
      By site-directed mutagenesis using the method of inverse polymerase chain
      reaction, cE and D cDNA mutant constructs were generated with changes to the RHD
      specific residues 350, 353, and 354 in the predicted sixth exofacial loop. Each
      mutant cDNA was subcloned into the pBabe puromycin retroviral vector, and
      supernatants were used to transduce K562 cells. Puromycin-resistant K562 clones
      were screened by flow cytometric analysis using a panel of monoclonal antibodies
      with specificities to ep (epitope) D1 through epD9. RESULTS: De novo expression
      of epD3 and epD9 was generated in the K562 cell lines expressing the mutated cE
      polypeptide (cE-Asp350His, Gly353Trp, Ala354Asn). Expression of c and E was
      unaffected. Conversely, the cells expressing the mutated D polypeptide
      demonstrated loss of expression of epD1, epD2, epD3, epD4, and epD9. CONCLUSION:
      The data provide strong evidence for the critical involvement of three amino
      acids, Asp350, Gly353, and Ala354, in the expression of epD3 and epD9 on the
      predicted sixth external domain of the D protein. This domain also appears to be
      essential for the expression of epD1, epD2, and epD4, as a loss of expression of
      these epitopes was observed in K562 cells transduced with the Dmut construct
      (encoding His350, Trp353, and Asn354). The K562/Dmut cell line has an identical
      molecular and serologic profile as the red cell D(IVb) phenotype, which confirms
      that retroviral gene transfer of Rh cDNA into K562 cells provides us with a
      powerful means by which to further map epitopes of D.

PMID- 9920163
TI  - Clinical evaluation of a solid-phase test for red cell antibody screening of
      pregnant women.
AB  - BACKGROUND: The aims of this study were to evaluate the results of a new solid
      phase screening test for detecting atypical red cell (RBC) antibodies in a large
      number of pregnant women and to compare these results to the clinical outcome of
      the newborn. STUDY DESIGN AND METHODS: A total of 38,700 infants born in
      Stockholm were studied retrospectively. Of these infants, 18,500 were born to
      pregnant women screened with the solid-phase test. Data were collected on all
      newborns with a positive direct antiglobulin test (DAT) and on infants requiring
      an exchange transfusion or a blood transfusion. These data were correlated to the
      screening results for the mothers. RESULTS: Of 409 DAT-positive newborns, a
      serologic explanation for the positive DAT was found in 349. Three hundred four
      cases were due to ABO incompatibility between mother and child; 19 of these
      infants needed an exchange transfusion. Forty-two cases were due to unexpected
      maternal RBC antibodies; 11 of these infants were given an exchange transfusion.
      All 11 were identified before birth. Three other infants had DAT-positive tests
      due to ABO incompatibility and to unexpected maternal RBC antibodies. CONCLUSION:
      ABO incompatibility is a major indication for exchange transfusion in DAT
      positive newborns. There was no evidence that the solid-phase screening test had
      failed to detect any clinically significant RBC antibodies. Finally, the results
      of this study do not indicate a need for routine screening of D+ women more than
      once during each pregnancy.

PMID- 9920164
TI  - NOR polyagglutination and Sta glycophorin in one family: relation of NOR
      polyagglutination to terminal alpha-galactose residues and abnormal glycolipids.
AB  - BACKGROUND: This report describes the characterization of polyagglutinable red
      cells (RBCs), identified in two generations of a Polish family. CASE REPORT:
      Untreated and modified RBCs of the proposita (TS) were tested by serologic
      methods, using human sera, antibodies, lectins, and inhibitors of agglutination.
      Moreover, glycophorins were characterized by sodium docecyl sulfate
      polyacrylamide gel electrophoresis and Western blotting, and glycolipids were
      purified, fractionated by thin-layer chromatography, and detected with Ricinus
      communis agglutinin I (RCA-I, specific for galactose residues) and Griffonia
      simplicifolia IB4 lectin (GSL-IB4, specific for Gal alpha1-3Gal- structure). Some
      of the experiments were also performed on RBCs of members of TS's family.
      RESULTS: Polyagglutination, found in four members of TS's family, was identified
      as the second case of an earlier described NOR polyagglutination. The
      polyagglutination was decreased by treating the RBCs with alpha-galactosidase and
      was inhibited by a neutral glycolipid fraction from NOR+ RBCs. Detection of
      neutral glycolipids of TS's RBCs on the thin-layer plate by RCA-I and GSL-IB4
      revealed the presence of components that were not detectable in control RBCs.
      Moreover, Western blotting of RBC membranes from five family members with
      glycophorin monoclonal antibodies and agglutination assays with anti-St(a) and
      anti-Dantu sera identified the presence of St(a) glycophorin in four members of
      the family, two of whom were NOR+ and two NOR-. CONCLUSION: Our results showed
      that two rare features of TS's RBCs, NOR polyagglutination and St(a) glycophorin,
      are inherited independently, and that NOR+ RBCs contain neutral glycolipids with
      an abnormal oligosaccharide structure, most likely terminated with alpha
      galactosyl residues.

PMID- 9920165
TI  - Mobilization of blood-derived stem and progenitor cells in normal subjects by
      granulocyte-macrophage- and granulocyte-colony-stimulating factors.
AB  - BACKGROUND: It was previously reported that the combination of granulocyte
      macrophage-colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) for 4
      days mobilized more primitive CD34+ subsets than did either G-CSF or GM-CSF
      alone. STUDY DESIGN AND METHODS: The studies determine the optimal number of days
      of growth factor dosing for mobilization and collection of peripheral blood
      progenitor cells, by increasing the days of administration of GM-CSF and/or G-CSF
      or employing the sequential administration of GM-CSF followed by G-CSF. Sixty
      normal subjects were given injections of G-CSF or GM-CSF alone; GM-CSF and G-CSF
      concurrently for 4, 5, or 6 days; or a sequential regimen of GM-CSF for 3 or 4
      days followed by G-CSF for 2 or 3 days. A 10-L apheresis was performed 24 hours
      after the last dose. RESULTS: The three most efficacious mobilization regimens
      consisted of sequential GM-CSF for 3 days followed by G-CSF for either 2 or 3
      days and G-CSF alone for 5 days. Each of these regimens resulted in the
      collection of significantly greater numbers of CD34+ cells by apheresis than any
      of the 4-day dosing regimens with G-CSF and/or GM-CSF (sequential GM-CSF/G-CSF: 3
      days/2 days = 3.58 +/- 0.53 x 106 CD34+ cells/kg; GM-CSF/G-CSF: 3 days/3 days =
      4.45 +/- 1.08 x 10(6) CD34+ cells/kg; G-CSF: 5 days = 3.58 +/- 0.97 x 10(6) CD34+
      cells/kg; all p<0.05 vs. G-CSF and/or GM-CSF for 4 days). Clonogenic assays
      generally paralleled the level of CD34+ cells. Regimens containing GM-CSF
      resulted in a higher percentage of the cells from primitive CD34+/CD38-/HLA-DR+
      subset than G-CSF alone. CONCLUSION: Compared with 4-day dosing regimens with G
      CSF and/or GM-CSF, mobilization of CD34+ cells in normal subjects using
      sequential GM-CSF for 3 days followed by G-CSF for 2 or 3 days or using G-CSF
      alone for 5 days increased the number CD34+ cells that can be collected by a
      single 10-L apheresis 24 hours after the last dose of cytokine.

PMID- 9920166
TI  - Improved collection of mobilized CD34+ hematopoietic progenitor cells by a novel
      automated leukapheresis system.
AB  - BACKGROUND: For simplification of blood cell transplantation, an automated
      apheresis system that exploits a dual-stage channel device for mononuclear cell
      (MNC) collection (AutoPBSC, designed for the COBE Spectra) was studied. STUDY
      DESIGN AND METHODS: The automated default software (AutoPBSC-Default) and three
      software modifications of the harvest frequency during leukapheresis, referred to
      as AutoPBSC-1.25, AutoPBSC-1.75, and AutoPBSC-2.75, were evaluated in comparison
      with the semiautomated Version 4.7 (V4.7) apheresis system in 119 leukapheresis
      procedures performed in 90 cancer patients treated with chemotherapy plus
      granulocyte-colony-stimulating factor. CD34+ cell and platelet collection
      efficiency (CE); volume and cell composition of the leukapheresis components; and
      patient platelet and red cell (RBC) loss during leukapheresis were measured.
      RESULTS: The majority of collection measures evaluated with the AutoPBSC compared
      favorably to those obtained with the V4.7. CD34+ cell CE increased from 55
      percent with V4.7 to 68 percent with the AutoPBSC-Default (p = 0.05). The
      AutoPBSC provided lower platelet contamination in the collected component (1.18 x
      10(11) vs. 2.26 x 10(11) with the V4.7; p<0.001). The volume of the AutoPBSC
      Default component was significantly lower (67 vs. 180 mL with the V4.7; p<0.001).
      The MNC purity of the AutoPBSC component was greater (52 vs. 28% with the V4.7;
      p<0.001), and the RBC contamination lower (AutoPBSC, 0.53 x 10(11) vs. 1.04 x
      10(11) with the V4.7; p<0.001). Modifications of the AutoPBSC to increase the
      harvest frequency by 1.25-, 1.75-, and 2.75-fold resulted in increased CD34+ cell
      CE (77%, 75%, and 83%, respectively; p<0.001 in all cases), but also in reduced
      numbers of circulating platelets, higher platelet contamination of the component,
      and lower MNC purity than were seen with the AutoPBSC-Default. CONCLUSION: The
      AutoPBSC offers the following advantages over the V4.7 system: a) better CE of
      CD34+ cells; b) reduced collection of platelets; c) reduced contamination of the
      leukapheresis component with granulocytes, platelets, and RBCs; d) reduced
      component volume; and e) automation.

PMID- 9920167
TI  - Variability of prothrombin time and activated partial thromboplastin time in the
      diagnosis of increased surgical bleeding.
AB  - BACKGROUND: Prothrombin time (PT) and activated partial thromboplastin time
      (APTT) are used to diagnose causes of increased surgical bleeding and to guide
      treatment of acquired coagulation factor deficiency. This study compared the
      sensitivity of various commercial PT and APTT tests in patients with dilutional
      coagulopathy. STUDY DESIGN AND METHODS: A prospective study was used to identify
      patients who experienced increased surgical bleeding during elective extensive
      (>10 spinal segments) spinal fusion and instrumentation. In patients with
      clinical signs of increased bleeding, blood was obtained to compare the
      sensitivity of various commercial PT and APTT tests. PT, PT ratio, the
      International Normalized Ratio (INR), APTT, and APTT ratio were compared for
      their sensitivity in the diagnosis of a dilutional coagulopathy. RESULTS: Sixteen
      patients experienced increased bleeding during surgery. Mean estimated blood
      volume lost exceeded 1 blood volume (1.14 +/- 0.28). PT and APTT test results
      varied markedly. In the most sensitive PT and APTT tests, the results were 1.5
      times the mean reference range values in all but on of the patients. The least
      sensitive combination of tests had results that were 1.5 times the mean reference
      range values in only 2 of 16 patients. Variability among tests was not reduced by
      the use of the PT or the APTT ratio, by the use of INR, or by incorporation of a
      measure of PT or APTT test sensitivity to factor-deficient serum. CONCLUSION: In
      surgical patients with dilutional coagulopathy, diagnostic and treatment
      decisions could depend on which PT and APTT test was used to determine the
      etiology of increased bleeding. This study indicates that the relationship
      between increased bleeding and an increased PT and APTT may be more difficult to
      define than is suggested by current practice guidelines. Each laboratory must
      establish guidelines based on reagent and instrument sensitivity to coagulation
      factor dilution.

PMID- 9920169
TI  - Long-term storage at -80 degrees C of hematopoietic progenitor cells with 5
      percent dimethyl sulfoxide as the sole cryoprotectant.
AB  - BACKGROUND: Hematopoietic progenitor cells (HPCs) can be cryopreserved and stored
      below -120 degrees C in liquid nitrogen or at -80 degrees C in mechanical
      freezers. STUDY DESIGN AND METHODS: The feasibility of long-term storage of HPCs
      at -80 degrees C was investigated. The studies included a comparison of 5- and 10
      percent dimethyl sulfoxide (DMSO) as cryoprotectant at various lengths of storage
      time. Mononuclear cell (MNC) recovery and viability and colony-forming unit
      granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) recovery
      assays were performed. The peripheral blood HPCs of 24 consecutive patients
      included in the program of autologous transplantation were studied. RESULTS: The
      MNC viability decreased progressively with the length of time from
      cryopreservation, reaching 32 percent after 31 months of storage. The recovery
      rates of CFU-GM and BFU-E also decreased progressively with the duration of
      frozen storage, to 50 and 43.5 percent, respectively, after 12 months and to 0
      percent (both) after 24 months. At 6 months of storage, MNC viability was 80
      percent, and CFU-GM and BFU-E recovery was 63.5 and 80.5 percent, respectively.
      There were no differences between MNCs cryopreserved with 5- or 10-percent DMSO
      in terms of cell viability. There were no differences between CFU-GM recovery or
      BFU-E recovery from HPCs cryopreserved in 5- or 10-percent DMSO. Patients given
      HPCs stored in these conditions for periods ranging between 123 and 202 days
      showed a complete and rapid hematologic recovery. CONCLUSION: HPCs can be
      cryopreserved at -80 degrees C with 5-percent DMSO and stored at -80 degrees C no
      longer than 6 months. A 5-percent DMSO concentration is comparable to a with 10
      percent concentration in terms of recovery and MNC viability.

PMID- 9920168
TI  - Effects of methylene blue-treated plasma on red cells and stored platelet
      concentrates.
AB  - BACKGROUND: Photochemical methods can effectively inactivate extracellular
      viruses and bacteria found in blood components. Treatment of plasma with
      methylene blue (MB), a phenothiazine dye, and visible light inactivates enveloped
      viruses including HIV-1. The effects of MB-treated plasma on cellular components
      stored in vitro have not been well characterized. STUDY DESIGN AND METHODS: MB
      treated plasma (83 microg MB/250 mL plasma) was added to single-donor platelets,
      stored AS-1 red cells (RBCs), irradiated RBCs, and frozen-deglycerolized RBCs. In
      vitro platelet assays performed after 1 and 5 days of storage in MB-treated
      plasma included pH, pO2, pCO2, HCO3, platelet number, lactate dehydrogenase,
      glucose, osmotic recovery, and CD62 expression. RBC components were examined at
      specific intervals for leakage of potassium, plasma hemoglobin level, and
      percentage of hemolysis. Direct antiglobulin tests, osmotic fragilities, and RBC
      antigen stability tests were also performed on RBCs stored in MB-treated plasma.
      Components stored with autologous plasma or nontreated allogeneic plasma served
      as controls. RESULTS: Similar storage-induced changes in pH, glucose, and
      platelet numbers, as well as increases in lactate dehydrogenase, CD62 expression,
      and lactate were seen in single-donor platelets stored with MB-treated and
      control plasma. Platelet morphology scores and osmotic recoveries were not
      altered. Plasma hemoglobin and potassium and percentage of hemolysis increased
      equally in the various RBC components stored with MB-treated or nontreated
      plasma. Osmotic fragility and RBC antigen stability were not appreciably altered
      by MB-treated plasma. CONCLUSION: Plasma treated by MB photoinactivation can be
      used for in vitro resuspension and storage of platelets or RBCs, because of the
      lack of influence of MB-treated plasma on a variety of in vitro platelet and RBC
      assays.

PMID- 9920170
TI  - Improved removal of white cells with minimal platelet loss by filtration of
      apheresis platelets during collection.
AB  - BACKGROUND: Filtration of apheresis platelets to remove white cells (WBCs)
      requires operator intervention after the collection procedure (postcollection
      filtration), which may cause variable and unsatisfactory filter performance (WBC
      removal and platelet loss). The MCS+ LN9000 apheresis system filters platelets
      through a WBC-reduction filter during each collection cycle (continuous
      filtration) at a flow rate of 15 to 25 mL per minute. Apheresis platelets
      obtained by continuous filtration were evaluated in terms of platelet loss, WBC
      removal, and platelet storage properties and then were compared to unfiltered
      apheresis platelets and to apheresis platelets that underwent postcollection
      filtration. Two WBC-reduction filters were tested (LRF6 and LRFXL). STUDY DESIGN
      AND METHODS: In 70 apheresis platelets, postcollection filtration was performed
      by using the LRF6 at flow rates of 80 mL per minute (n = 30) and 50 mL per minute
      (n = 30) and the LRFXL at 50 mL per minute (n = 10). One hundred fifty-eight
      apheresis platelets underwent continuous filtration through the LRF6 (n = 58) or
      the LRFXL (n = 100). Unfiltered apheresis platelets (controls) (n = 30) were
      obtained by the same collection protocol. RESULTS: Estimated platelet loss with
      continuous filtration was 7 percent for the LRFXL and 3 percent for the LRF6. A
      reduction in the filtration flow rate from 80 to 50 mL per minute with
      postcollection filtration through the LRF6 resulted in markedly lower WBC levels,
      with 10 percent versus 57 percent of the apheresis platelets having WBC counts <1
      x 10(5), respectively. Additional improvements in WBC removal were found with
      continuous filtration; 85 percent of the apheresis platelets filtered with the
      LRF6 and 100 percent of the apheresis platelets filtered with the LRFXL had WBC
      counts <1 x 10(5). CONCLUSIONS: Continuous or postcollection filtration of
      freshly collected apheresis platelets resulted in minimal platelet loss. Better
      WBC removal from apheresis platelets was obtained with continuous filtration than
      with postcollection filtration, likely because of the slower flow rate. Platelet
      storage quality was not affected by filtration.

PMID- 9920171
TI  - Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals
      at high or low risk for blood-borne or sexually transmitted viruses: evidence of
      sexual and parenteral transmission.
AB  - BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV-C)/hepatitis
      G virus (HGV) infection showed a high prevalence of asymptomatic carriers in
      blood donors and in populations at risk for blood-borne viruses. However, by
      using only viral RNA polymerase chain reaction, those studies underestimated the
      true spread of GBV-C/HGV infection. The combined detection of GBV-C/HGV RNA and
      of anti-E2 (which reflects recovery from infection) is necessary to define
      accurately the prevalence of GBV-C/HGV. STUDY DESIGN AND METHODS: The presence of
      both anti-E2 and GBV-C/HGV RNA was searched for in 1438 serum samples collected
      from various groups of individuals at low or high risk for blood-borne or
      sexually transmitted viruses (blood donors, organ donors, unselected pregnant
      women, immunocompetent or immunodepressed multiply transfused patients, HIV
      positive or HIV-negative homosexual men, intravenous drug addicts). RESULTS: The
      presence of GBV-C/HGV RNA and/or anti-E2 (exposure to GBV-C/HGV) was frequent in
      populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV
      appeared also to be sexually transmitted, with transmission from male to female
      more efficient than vice versa. A particularly elevated level of exposure to GBV
      C/HGV was observed in homosexual men. In immunocompetent individuals, the
      prevalence of anti-E2 was about twice that of GBV-C/HGV RNA, which suggests the
      frequency of recovery from GBV-C/HGV infection. Most of the GBV-C/HGV RNA
      positive individuals had no biochemical evidence of liver damage. CONCLUSIONS:
      GBV-C/HGV is frequent in populations at risk for blood-borne or sexually
      transmitted viruses. GBV-C/HGV is not a hepatitis virus, and it seems appropriate
      to rename it.

PMID- 9920172
TI  - Prevalence of GB virus type C/hepatitis G virus RNA and anti-E2 among blood
      donors in Southeastern France.
AB  - BACKGROUND: The purpose of the study was to analyze serologic and molecular
      markers of the GB virus type C/hepatitis G virus (GBV-C/HGV) infection in
      voluntary blood donors from Southeastern France. STUDY DESIGN AND METHODS: Sera
      were tested for the presence of GBV-C/HGV RNA by reverse transcriptase-polymerase
      chain reaction and that of antibodies to the GBV-C/HGV E2 (anti-E2) antigen by an
      enzyme-linked immunosorbent assay. A first cohort (1660 blood donors) was tested
      prospectively and a second cohort (238 samples with hepatitis markers) was tested
      retrospectively. Donors in the prospective study were questioned for possible
      risk factors of virus transmission. Amplification products were sequenced and
      subjected to phylogenetic analysis. RESULTS: Approximately 2.6 percent of
      individuals accepted for blood donation and 15.4 percent with positive hepatitis
      C virus serologic tests carried GBV-C/HGV RNA. Anti-E2 was detected in these two
      populations in approximately 12 percent and 48 percent of donors, respectively.
      Moderate relative risks were found only in tattooed or pierced individuals (1.82)
      and health care workers (2.45). Almost all strains were located in the same
      phylogenetic branch as HGV Group 2. CONCLUSION: Though a large proportion of the
      donors tested have been in contact with GBV-C/HGV, no elevated relative risk of
      infection was identified. The phylogenetic distribution of viral strains suggests
      that the infection is endemic in this population.

PMID- 9920173
TI  - Prevalence of HLA sensitization in female apheresis donors.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious
      complication of plasma-containing blood components. Studies have implicated HLA
      antibodies along with biologically active lipids in stored blood in the
      pathogenesis of TRALI. It has been proposed that the exclusion of HLA-untested,
      multiparous donors of plasma-rich components, including plasma and single-donor
      apheresis platelets, would substantially reduce the risk of TRALI. STUDY DESIGN
      AND METHODS: To investigate the feasibility of such an exclusion, 332 female
      plateletpheresis donors with a record of over 9000 donations, none of which were
      associated with TRALI, were studied. RESULTS: Seventeen percent of female donors
      demonstrated HLA sensitization. Parity and HLA sensitization were significantly
      correlated (p<0.0001), with sensitized donors having an average of 2.9 (+/- 0.6
      95% CI) prior pregnancies and unsensitized donors having an average of 1.8 (+/-
      0.2 95% CI) prior pregnancies. The percentage of HLA-sensitized women with 0, 1
      to 2, and > or = 3 pregnancies was 7.8, 14.6, and 26.3, respectively. CONCLUSION:
      These findings confirm the hypothesis that multiparous women (> or = 3
      pregnancies) represent an increased potential risk for TRALI. However, the
      exclusion of multiparous plateletpheresis donors would eliminate one-third of our
      female donor pool. Screening such donors for HLA sensitization may represent the
      optimal approach for identifying donors at risk for causing TRALI, but this still
      would result in the deferral of 8 percent of female plateletpheresis donors. At
      present, prospective screening to identify donors at risk for causing TRALI is
      not justified.

PMID- 9920174
TI  - Current status of solvent/detergent-treated frozen plasma, whole-blood inline
      filtration, and Creutzfeldt-Jakob disease.

PMID- 9920175
TI  - Hypotensive reactions during transfusion: is bradykinin the culprit?

PMID- 9920176
TI  - Variation in Lan expression.

PMID- 9920177
TI  - Hemolysis and acute renal failure due to the administration of albumin diluted in
      sterile water.

PMID- 9920178
TI  - The amphetamine-like reinforcing effect and mechanism of L-deprenyl on
      conditioned place preference in mice.
AB  - The present study investigated the reinforcing effect of L-deprenyl on
      conditioned place preference in mice and its mechanism. Conditioned place
      preference was induced by 10 and 25 mg/kg L-deprenyl in a dose-dependent fashion
      during five consecutive conditioning days, and its reinforcing property was about
      five-fold less potent than that of L-amphetamine. Pretreatment with the dopamine
      antagonist, haloperidol (1 mg/kg i.p.), effectively blocked the place preference
      produced by L-deprenyl (10 and 25 mg/kg i.p.) and L-amphetamine (2 and 5 mg/kg
      i.p.), but haloperidol itself produced no place aversion. The neurotoxin, 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 30 mg/kg did not modify the
      place preference induced by both L-deprenyl and L-amphetamine, though the
      dopamine concentration in striata assayed by high performance liquid
      chromatography with electrochemical detection (HPLC-EC) was significantly
      reduced. These results suggest that L-deprenyl has amphetamine-like reinforcing
      properties. The reinforcing effect of L-deprenyl may be mediated by central
      dopaminergic neuronal systems, while the nigrostriatal dopaminergic pathway is
      not involved.

PMID- 9920179
TI  - Characterization of the muscarinic receptor subtype mediating pilocarpine-induced
      tremulous jaw movements in rats.
AB  - Four muscarinic receptor antagonists with varying selectivities for the four
      pharmacologically-defined muscarinic receptor subtypes (M1-M4) were administered
      into the lateral ventricle to determine their relative potency in reducing
      tremulous jaw movements induced by i.p. injection of the muscarinic receptor
      agonist pilocarpine (4.0 mg/kg). All four muscarinic receptor antagonists reduced
      tremulous jaw movements in a dose-dependent manner, with the following rank order
      of potency: scopolamine > methoctramine > or = telenzepine > pirenzepine. This
      pattern is inconsistent with the rank order of affinity of these agents at the
      muscarinic M1 receptor, and is consistent with their rank order of affinity at
      muscarinic M2 or M4 receptors. Because tremulous jaw movements are related to
      striatal function, and the muscarinic M4 receptor is more predominant than the
      muscarinic M2 receptor as a post-synaptic receptor in striatum, the present
      results suggest that pilocarpine induces jaw movements due to muscarinic M4
      receptor stimulation. In view of the hypothesized relation between parkinsonism
      and cholinomimetic-induced jaw movements, these data suggest that a centrally
      acting muscarinic M4 receptor antagonist could be useful as an antiparkinsonian
      agent.

PMID- 9920180
TI  - Localisation of hepatic vascular resistance sites in the isolated dual-perfused
      rat liver.
AB  - The locations of the vascular resistance sites which regulate vascular tone in
      the hepatic arterial and portal venous vasculatures of the rat liver were
      identified using a new, in vitro, dual-perfused liver preparation. Twelve livers
      of male Wistar rats were perfused via the hepatic artery and portal vein at fixed
      flow and at physiological pressure. Dose-related vasoconstriction to injections
      or infusions of noradrenaline was measured as transient or sustained increases in
      perfusion pressure, respectively, in the hepatic arterial and portal venous
      vasculatures. Direct injections/infusions of noradrenaline refer to those
      administered into the vasculature from which pressure was recorded, e.g., the
      effects of hepatic arterial (direct) injections/infusions of noradrenaline upon
      hepatic arterial perfusion pressure. Indirect injections/infusions of
      noradrenaline were those administered to the adjacent afferent vasculature, e.g.,
      the effects of portal venous (indirect) injections of noradrenaline upon hepatic
      arterial perfusion pressure. The converse applies for recordings of portal venous
      perfusion pressure. The -log(M) ED50 values to direct (hepatic arterial) and
      indirect (portal venous) injections in the hepatic artery were 4.25+/-0.20 and
      3.40+/-0.10, respectively, and were significantly different (P < 0.01, Student's
      unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect
      (hepatic arterial) injections in the portal vein were 3.91+/-0.08 and 3.85+/
      0.11, respectively, and were not significantly different (P > 0.05, Student's
      unpaired t-test). Similarly, the -log(M) ED50 values to direct (hepatic arterial)
      and indirect (portal venous) infusions in the hepatic artery were 5.28+/-0.11 and
      3.75+/-0.12, respectively, and were significantly different (P < 0.01, Student's
      unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect
      (hepatic arterial) infusions in the portal vein were 5.31+/-0.19 and 5.70+/-0.16,
      respectively, and were not significantly different (P > 0.05, Student's unpaired
      t-test). These results demonstrated that there is little transfer of
      noradrenaline from the portal venous to the hepatic arterial resistance sites,
      but significant transfer from the hepatic artery to the portal venous suggesting
      that; (a) the portal venous resistance sites are located at the sinusoidal or
      post-sinusoidal level; and (b) the hepatic arterial resistance sites are located
      at the pre-sinusoidal level.

PMID- 9920181
TI  - New model of cytoprotection/adaptive cytoprotection in rats: endogenous small
      irritants, antiulcer agents and indomethacin.
AB  - Adaptive cytoprotection in the stomach was originally defined by applying the
      exogenous irritants only. The contribution of endogenous irritants as inductors
      of initial lesions was not specially evaluated. No attempt was made to either
      focus antiulcer agent activity on adaptive cytoprotection, or split their
      'cytoprotection' into complex adaptive cytoprotective activity and simple
      cytoprotective effects. Agents had so far not been applied simultaneously with
      the second challenge with ethanol (or irritant), when differences between
      cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for
      24 h in rats was introduced as new model for analyzing cytoprotection/adaptive
      cytoprotection. The contribution of the up-normal level of endogenous irritants
      and the endogenous small irritant-induced minor lesions during the adaptive
      cytoprotection were studied. The effect of late challenge with 96% ethanol in the
      presence of an up-normal level of endogenous irritants and endogenous small
      irritant-induced minor lesions was compared with results of classic studies of
      ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents
      or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic
      studies, were given at several points during injury induction: (i) surgery, (ii)
      mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable
      period following either mild ethanol or surgery). Their effects were compared in
      rats treated as follows: exogenous irritant studies (96% or 20% ethanol),
      exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol),
      endogenous irritant studies (gastrojejunal anastomosis for 24 h), and
      endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before
      96% ethanol). Characteristic of the various irritants differed: the (preceding)
      small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous
      irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion,
      duodenal reflux in gastric content in rats with termino-lateral gastrojejunal
      anastomosis) (endogenous irritant studies)). These factors caused modifications
      of agents' activities not, as initially thought, giving simple 'cytoprotection',
      but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective
      and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had
      only cytoprotective activity (exogenous irritant-studies), whereas
      pentadecapeptide BPC157 (10 microg or 10 ng), and omeprazole (10 mg) had mainly
      adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both
      cytoprotective and adaptive cytoprotective activities (exogenous/exogenous
      irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.),
      showed that only events preceding the late challenge with ethanol may be
      prostaglandin-dependent in both models. The second, adaptive cytoprotective part,
      seen after late ethanol challenge, may be either prostaglandin-dependent
      (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous
      irritant studies). Both spontaneous lesion reduction, as an essential mechanism
      of adaptive cytoprotection, and the further lesion reduction by agents, such as
      pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as
      an essential link between the various reactions in cytoprotection/adaptive
      cytoprotection.

PMID- 9920182
TI  - The alleged dopamine D1 receptor agonist SKF 83959 is a dopamine D1 receptor
      antagonist in primate cells and interacts with other receptors.
AB  - So far, no clear correlation has been found between the effects of dopamine D1
      receptor agonists on motor behavior in primate models of Parkinson's disease and
      their ability to stimulate adenylate cyclase in rats, the benzazepine SKF 83959
      (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-]H- 3
      benzazepine) being the most striking example. Since this discrepancy might be
      attributed to: (A) the different species used to study these effects or (B) the
      interaction of SKF 83959 with other catecholamine receptors, the aims of this
      study were: (1) to study the ability of SKF 83959 to stimulate adenylate cyclase
      in cultured human and monkey glial cells equipped with dopamine D1 receptors and
      (2) to evaluate the affinity for and the functional interaction of SKF 83959 with
      other catecholamine receptors. Binding studies revealed that SKF 83959 displayed
      the highest affinity for the dopamine D1 receptor (pKi=6.72) and the alpha2
      adrenoceptor (pKi=6.41) and moderate affinity for the dopamine D2 receptor and
      the noradrenaline transporter. In monkey and human cells, SKF 83959 did not
      stimulate cyclic adenosine monophosphate (cAMP) formation to a significant
      extent, but antagonized very potently the dopamine-induced stimulation of cAMP
      formation in both cell types. The compound stimulated basal dopamine outflow and
      inhibited depolarization-induced acetylcholine release only at concentrations >
      10 microM. Finally, SKF 83959 concentration dependently increased electrically
      evoked noradrenaline release, indicating that it had alpha2-adrenoceptor blocking
      activity and interfered with the noradrenaline transporter. In conclusion, SKF
      83959 is a potent dopamine D1 receptor and alpha2-adrenoceptor antagonist. Thus,
      the anti-parkinsonian effects of SKF 83959 in primates are not mediated by
      striatal dopamine D1 receptors coupled to adenylate cyclase in a stimulatory way.

PMID- 9920183
TI  - Effects of HMG-CoA reductase inhibitors on excitation-contraction coupling of rat
      skeletal muscle.
AB  - 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors currently
      used as cholesterol-lowering drugs produce side effects in patients, one of which
      is myopathy. In the present study we compared the effect of a 3-month chronic
      treatment with two different compounds, simvastatin and pravastatin, on the
      excitation-contraction coupling of rat skeletal muscle fibers, the mechanism
      which links membrane depolarization to the movements of cytosolic Ca2+ from
      intracellular stores. The voltage threshold for mechanical activation of extensor
      digitorum longus muscle fibers in response to depolarizing pulses of various
      durations was studied in vitro by the two intracellular microelectrode method in
      'point' voltage clamp mode. Simvastatin (5-50 mg/kg) modified the mechanical
      threshold of striated fibers in a dose-dependent manner. The muscle fibers of
      rats treated with 10 mg/kg and 50 mg/kg of simvastatin needed significantly less
      depolarization to contract than did untreated fibers at each pulse duration,
      suggesting that levels of cytosolic Ca2+ were higher. Consequently, the rheobase
      voltage for fiber contraction was significantly shifted toward more negative
      potentials with respect to controls by 2.4 mV and 7.1 mV in the 10 mg/kg and 50
      mg/kg simvastatin-treated animals, respectively. Pravastatin treatment at 100
      mg/kg did not produce any alteration of excitation-contraction coupling since the
      rheobase voltage was similar to that of controls. The different physicochemical
      properties of the two drugs may underlie the different effect observed because
      lipophilic agents, such as simvastatin, have been shown to affect sterol
      biosynthesis in many tissues, whereas the hydrophilic pravastatin is hepato
      selective.

PMID- 9920184
TI  - The nociceptin receptor-mediated inhibition of the rat rostral ventrolateral
      medulla neurons in vitro.
AB  - The recently available antagonist selective for novel nociceptin receptor, [Phe1
      psi(CH2-NH)Gly2]NC(1-13)NH2, was utilized in this study to verify specificity of
      nociceptin receptor in mediating the nociceptin-induced inhibition of electrical
      activity of neurons in the rostral ventrolateral medulla of rat brain slices.
      Perfusion of nociceptin (10 nM) considerably reduced spontaneously firing
      frequency of the medullary neurons. Co-perfusion of [Phe1 psi(CH2-NH)Gly2]NC(1
      13)NH2 (10 microM) completely blocked the nociceptin-induced depression of the
      neuronal activity. Blocking effect of [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2 was
      concentration-dependent. However, the nociceptin antagonist did not modify basal,
      and opioid peptide enkephalin-depressed, firing rates of the neurons. In contrast
      to [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2, the non-selective opioid receptor
      antagonist naloxone (10 microM) failed to affect the nociceptin inhibition even
      though naloxone at a lower concentration (1 microM) readily blocked enkephalin
      induced depression of the neuronal activity. These data indicate that the
      nociceptin-induced inhibition of spontaneous discharge of the rostral
      ventrolateral medulla neurons is specifically mediated by [Phe1 psi(CH2
      NH)Gly2]NC(1-13)NH2-sensitive nociceptin receptors distinct from typical naloxone
      sensitive opioid receptors.

PMID- 9920185
TI  - Heterologous desensitization of muscarinic receptors by P2Z purinoceptors in rat
      parotid acinar cells.
AB  - We studied the heterologous desensitization of muscarinic receptors by ATP in
      fura-2-loaded rat parotid acinar cells. Exposure to ATP or 3'-o-(4-benzoyl)
      benzoyl-ATP shortened the duration and decreased the magnitude of acetylcholine
      induced Ca2+ release from intracellular Ca2+ stores in a dose-dependent manner.
      The shortening was observed only in an early stage of desensitization (within 20
      s), whereas the decrease in the magnitude of the response was dependent upon the
      time the cells were exposed to the nucleotides. Atropine induced a profound
      shortening during the progressive decrease in the magnitude of acetylcholine
      induced Ca2+ release. 3'-o-(4-Benzoyl) benzoyl-ATP did not induce an increase in
      the cytosolic Ca2+ concentration when the cells were incubated in the Ca2+- and
      Na+-free medium, but it did induce a strong desensitization of muscarinic
      receptors. The specific protein kinase C inhibitor bisindoylmaleimide
      resensitized the 3'-o-(4-benzoyl) benzoyl-ATP-treated muscarinic receptors.
      Phorbol 12-myristate 13-acetate potentiated the desensitization of muscarinic
      receptors. Ceramides that prevent the activation of phospholipase D resensitized
      the 3'-o-(4-benzoyl) benzoyl-ATP-treated muscarinic receptors. These results
      suggest that ATP, acting through P2Z purinoceptor-mediated phospholipase D, may
      produce a Ca2+-independent protein kinase C. Heterologous desensitization of
      muscarinic receptors by protein kinase C may shorten the duration and decrease
      the magnitude of acetylcholine-induced Ca2+ release.

PMID- 9920186
TI  - Effects of endogenous and exogenous nitric oxide on endothelin-1 production in
      cultured vascular endothelial cells.
AB  - The effects of various spontaneous nitric oxide (NO) donors and NO synthase
      inhibitors on endothelin- production were examined using porcine cultured aortic
      endothelial cells. NO donors such as (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5
      nitro-3-hexanamide (NOR 2), (+/-)-(E)-4-ethyl-2-[( E)-hydroxyimino]-5-nitro-3
      hexanamide (NOR 3) and (+/-)-N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen
      1- yl]-3-pyridine carboxamide (NOR 4) suppressed effectively the release of
      endothelin-1 from the cells. Endothelin-1 mRNA expression was also attenuated by
      these compounds. Other NO donors such as 3-[2-hydroxy-1-(1-methylethyl)-2
      nitrosohydrazino]-1-propanamin e (NOC 5), 2,2'-(hydroxynitrosohydrazino)bis
      ethanamine (NOC 18), s-nitroso-n-acetyl-DL-penicillamine, N-morpholino
      sydnonimine (SIN-1) had no effects on endothelin-1 production. Endothelial
      intracellular cyclic guanosine monophosphate (cGMP) levels were significantly
      increased by all NO donors. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a
      selective soluble guanylyl cyclase inhibitor, had no effect on the NOR 3-induced
      decrease in endothelin-1 secretion, although cGMP production was abolished by
      ODQ. NOR 3 also inhibited endothelin-1 secretion even in the presence of 2-(4
      carboxyphenyl)-4,4,5,5-tetrametylimidazole-1-oxyl 3-oxide (carboxy-PTIO), a NO
      scavenger. NOR 3-induced inhibitory effects on endothelin-1 secretion were
      abolished by preincubation of the compound in phosphate-buffered saline (37
      degrees C, 4 h), a procedure by which about 98% of the parent compound's ability
      to release NO was lost. NO synthase inhibitors such as N(G)-nitro-L-arginine,
      N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine methyl ester (L-NAME)
      enhanced prepro endothelin-1 mRNA expression and significantly increased
      endothelin-1 release from endothelial cells. Endothelin-1 secretion was also
      increased effectively by carboxy-PTIO or ODQ. When the cells were exposed to L
      NAME with carboxy-PTIO or ODQ, no significant further increase in endothelin-1
      release was observed. These results suggest that endogenous NO inhibits
      endothelin-1 production through guanylyl cyclase/cGMP-dependent mechanisms. In
      contrast, it seems unlikely that exogenous NO has an inhibitory effect on
      endothelin-1 production in endothelial cells. NOR compounds inhibit endothelin-1
      production perhaps through NO/cGMP-independent mechanisms, i.e., through an
      unknown effect of the parent compound itself.

PMID- 9920187
TI  - Anandamide transport inhibition by the vanilloid agonist olvanil.
AB  - The structural similarities between the anandamide transport inhibitor N-(4
      hydroxyphenyl)-arachidonylamide (AM404) and the synthetic vanilloid agonist
      olvanil [(N-vanillyl)-9-oleamide], prompted us to investigate the possibility
      that olvanil may interfere with anandamide transport. The intracellular
      accumulation of [3H]anandamide by human astrocytoma cells was prevented by
      olvanil with a Ki value of 14.1+/-7.1 microM. By contrast, capsaicin [(8-methyl-N
      vanillyl)-6-noneamide], a plant-derived vanilloid agonist, and capsazepine (N-[2
      (4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2 H-2-benzazepine-2
      carbothioamide), a vanilloid antagonist, had no such effect (Ki > 100 microM).
      These results indicate that, although less potent than AM404 (Ki 2.1+/-0.2
      microM), olvanil may reduce anandamide clearance at concentrations similar to
      those needed for vanilloid receptor activation.

PMID- 9920188
TI  - Reliability of scores on the Stroke Rehabilitation Assessment of Movement
      (STREAM) measure.
AB  - BACKGROUND AND PURPOSE: The Stroke Rehabilitation Assessment of Movement (STREAM)
      is a new clinical measurement tool for evaluating the recovery of voluntary
      movement and basic mobility following stroke. This article presents the results
      of 3 substudies examining the reliability (interrater and intrarater) and
      internal consistency of STREAM scores. SUBJECTS AND METHODS: A "direct
      observation reliability study" was conducted on 20 patients who had strokes and
      were in a rehabilitation setting. Pairs of raters from a group of 6 participating
      therapists provided data to judge interrater agreement. A "videotaped assessments
      reliability study" was done to assess intrarater and interrater agreement on the
      scoring of videotaped performances using the STREAM measure and involved 4
      videotaped assessments that were viewed and rated on 2 occasions by 20 physical
      therapists. The internal consistency of the STREAM scores was evaluated for 26
      patients who had strokes and who demonstrated the full range of motor ability.
      RESULTS: The reliability of the STREAM scores was demonstrated by
      generalizability correlation coefficients of .99 for total scores and of .96 to
      .99 for subscale scores. The internal consistency of the STREAM scores was
      demonstrated by Cronbach alphas of greater than .98 on the subscales and overall.
      CONCLUSION AND DISCUSSION: These high levels of reliability support the use of
      the STREAM instrument for the measurement of motor recovery following stroke.
      Further work on the validity and responsiveness of the STREAM measure is in
      progress.

PMID- 9920189
TI  - Fetal and neonatal hand movement.
AB  - BACKGROUND AND PURPOSE: Fetal movement occurs early in human gestation and can be
      observed by ultrasound imaging. This was a descriptive study of fetal hand
      movements from 14 weeks of gestation to postnatal day 1. The purpose of the study
      was to identify specific hand movements and their developmental trends in order
      to better understand low-risk human development. SUBJECTS: Twenty-one women with
      low-risk pregnancies were identified from a university obstetrics clinic. Their
      fetuses or neonates were the focus of this study. METHODS: Ultrasound imaging was
      used at 14, 20, 26, 32, and 37 weeks of gestation, and videotaping was used at 1
      day after birth. Between 12 and 16 minutes of usable imaging was obtained at each
      fetal age, and 24 minutes of videotape was collected neonatally. The duration and
      frequency of 7 hand movements were determined and reliably scored. Nonparametric
      analyses were used. RESULTS: Fetal and neonatal movements did not appear to be
      random, and they appeared to be directed or aimed at specific targets. Fetal
      movement was variable throughout gestation. Differences occurred between fetal
      and neonatal data. Durations of certain hand movements provided data that
      exhibited some developmental trends, such as decreasing linear trends and
      regression-type U curves. Fetal movements to or at the head and face and the
      observations scored at 32 weeks of gestation were the best predictors of neonatal
      movement. CONCLUSION AND DISCUSSION: Results suggest the potential for fetal
      movement to be observed and scored reliably, with scores used to further our
      understanding of the development of human movement.

PMID- 9920190
TI  - Ketoprofen tissue permeation in swine following cathodic iontophoresis.
AB  - BACKGROUND AND PURPOSE: Pharmacokinetic assessment of drug tissue permeation
      following iontophoresis is limited. The depth of ketoprofen tissue permeation
      following cathodic iontophoresis (4 mA, 40 minutes) and the stereoselectivity of
      drug delivery were examined in this study. SUBJECTS: Ketoprofen (750 mg) was
      iontophoresed onto one porcine medial thigh, with passive drug permeation
      conducted on the other thigh. METHODS: Skin, subcutaneous fascia, and muscle
      biopsies from the drug delivery sites were harvested and stored separately, and
      the "R" and "S" ketoprofen enantiomers were determined. Results. Iontophoretic
      and passive applications yielded equivalent total ketoprofen concentrations in
      the skin and fascia. In contrast, multivariate analysis demonstrated that the
      ketoprofen concentration in the first centimeter of muscle following
      iontophoresis was greater than the drug concentration in the deeper underlying
      muscle layers and greater than that delivered to any muscle layer following
      passive delivery. No transcutaneous stereoselective delivery) of ketoprofen was
      detected. CONCLUSION AND DISCUSSION: Compared with passive delivery,
      iontophoresis enhances nonstereoselective ketoprofen permeation into the fascia
      muscle interface. With delivery to deeper tissue sites, however, there is no
      apparent enhancement over passive application.

PMID- 9920191
TI  - Manipulation of the cervical spine: risks and benefits.
AB  - Manipulation of the cervical spine (MCS) is used in the treatment of people with
      neck pain and muscle-tension headache. The purposes of this article are to review
      previously reported cases in which injuries were attributed to MCS, to identify
      cases of injury involving treatment by physical therapists, and to describe the
      risks and benefits of MCS. One hundred seventy-seven published cases of injury
      reported in 116 articles were reviewed. The cases were published between 1925 and
      1997. The most frequently reported injuries involved arterial dissection or
      spasm, and lesions of the brain stem. Death occurred in 32 (18%) of the cases.
      Physical therapists were involved in less than 2% of the cases, and no deaths
      have been attributed to MCS provided by physical therapists. Although the risk of
      injury associated with MCS appears to be small, this type of therapy has the
      potential to expose patients to vertebral artery damage that can be avoided with
      the use of mobilization (nonthrust passive movements). The literature does not
      demonstrate that the benefits of MCS outweigh the risks. Several recommendations
      for future studies and for the practice of MCS are discussed.

PMID- 9920192
TI  - Quadriceps femoris and hamstring muscle function in a person with an unstable
      knee.
AB  - BACKGROUND AND PURPOSE: The purpose of this case report is to describe the
      evaluation, treatment, and short-term outcome for an individual with chronic,
      progressively worsening instability of the knee during gait associated with
      anterior cruciate ligament (ACL) insufficiency. CASE DESCRIPTION: The patient was
      a 34-year-old man who sustained bilateral ACL injuries. Subsequently, an
      autograft reconstruction of the left knee ACL was performed. Eight months post
      reconstruction, the left knee was unstable despite bracing. Gait analysis and
      tests to determine the presence of muscle inhibition were performed prior to and
      after 12 weeks of training. Isometric torque of the knee extensors and flexors
      was measured with the knee in 90 degrees of flexion. A training program primarily
      consisted of electromyographic biofeedback during thigh muscle exercises, balance
      exercises, and gait. OUTCOMES: Muscle inhibition decreased and maximal isometric
      knee flexion and extension torques increased during the 12-week training period.
      Gait analysis demonstrated a 50% decrease in the maximum knee extensor moment and
      an increase in walking speed. DISCUSSION: Selected gait variables, torque
      production, and muscle inhibition may change in a person with an unstable knee.
      The measurement of variables that have previously been documented as mechanisms
      of knee instability during walking allows for the selection of a specific
      treatment approach.

PMID- 9920194
TI  - Sincerity of effort.

PMID- 9920195
TI  - Senescence-accelerated mouse (SAM) as an animal model of senile dementia:
      pharmacological, neurochemical and molecular biological approach.
AB  - To elucidate the fundamental mechanism of age-related deficiencies of learning
      and to develop effective drugs for intervention in age-related diseases such as
      learning dysfunctions, pertinent animal models that have characteristics closely
      similar to human dysfunctions should be established. SAM (senescence-accelerated
      mouse) has been established as a murine model of the SAM strains, groups of
      related inbred strains including nine strains of accelerated senescence-prone,
      short-lived mice (SAMP) and three strains of accelerated senescence-resistant,
      long-lived mice (SAMR). SAMP-strain mice show relatively strain-specific age
      associated phenotypic pathologies such as shortened life span and early
      manifestation of senescence. Among the SAMP-strain mice, SAMP8 mice show an age
      related deterioration in learning ability. Here, the neuropathological,
      neurochemical and pharmacological features of SAM are reported, especially for
      SAMP8. Moreover, the effects of several drugs on the biochemical and behavioral
      alterations in SAMP8 and the etiologic manifestation of accelerated senescence
      are also discussed.

PMID- 9920193
TI  - Does growth hormone therapy in conjunction with resistance exercise increase
      muscle force production and muscle mass in men and women aged 60 years or older?
AB  - Improved muscle protein mass and increments in maximum voluntary muscle force
      have rarely been observed in men and women aged 60 years and older who were
      treated with rhGH. Although rhGH administration has been reported to increase
      lean body mass in older men and women, it is doubtful that this increase is
      localized to skeletal muscle contractile proteins. When rhGH administration was
      combined with 16 weeks of resistance exercises, increases in muscle mass, muscle
      protein synthesis, and muscle force were not greater in the rhGH-treated group
      than in a weight training group that received placebo injections. Side effects of
      rhGH treatment in elderly people are prevalent, not trivial, and further limit
      its usefulness as an effective anabolic agent for promoting muscle protein
      accretion in men and women. In particular, the induction of insulin resistance
      and carpal tunnel compression reduces the efficacy of rhGH replacement therapy in
      elderly individuals. The evidence for a GH-induced increase in human skeletal
      muscle protein and maximum voluntary muscle force is weak. The optimum dose and
      GH-replacement paradigm (GHRH, GH-secretagogues) have not been identified.
      Whether rhGH therapy improves muscle protein mass and force in individuals with
      severe cachexia associated with major trauma, burns, surgery, or muscular
      dystrophy is controversial and under investigation.

PMID- 9920196
TI  - ATP receptors for the protection of hippocampal functions.
AB  - The inhibitory effects of extracellular adenosine 5'-triphosphate (ATP) are
      reviewed in the present paper. ATP inhibits the release of the excitatory
      transmitter glutamate and stimulates the release of the inhibitory transmitter
      GABA from hippocampal neurons. Also, ATP activates potassium conductance directly
      through G protein, resulting in hyperpolarization of membrane potential. ATP
      activates microglia to secrete plasminogen that promotes the development of
      mesencephalic dopaminergic neurons and enhances neurite outgrowth from explants
      of neocortical tissue. Moreover, ATP may protect hippocampal neurons from
      excitotoxic cell death by preserving mitochondrial function. Thus, ATP may have a
      role in the protection of the function of hippocampus from over-stimulation by
      glutamate.

PMID- 9920197
TI  - Subspecies-specific targeting mechanism of protein kinase C.
AB  - To clarify the subspecies-specific functions of protein kinase C (PKC), we
      constructed cDNAs encoding gamma-, epsilon- and delta-PKC fused with green
      fluorescent protein (GFP). All fusion proteins had enzymological and
      immunological characteristics similar to those of native PKCs. When expressed in
      CHO-K1 cells, each fusion protein showed a specific subcellular localization.
      Their translocations induced by various stimulation were also diverse. For
      example, ATP translocated gamma-, epsilon- and delta-PKC-GFP in the cytoplasm to
      the plasma membrane within 30 sec with a return to the cytoplasm in 3 min,
      whereas TPA induced slow and irreversible translocation of all subspecies to the
      plasma membrane. Fatty acids also induced the translocation of gamma- and epsilon
      PKC-GFP, but the two PKC subspecies showed distinct translocation and sensitivity
      to various fatty acids. Furthermore, we revealed that the PKC translocation
      requires neither the kinase activity of PKC nor its association with cytoskeletal
      proteins such as F-actin. These results indicate that each subspecies has a
      spatially and temporally different targeting mechanism that depends on the
      extracellular and intracellular signals, contributing to the subspecies-specific
      functions of PKC. These remarkable findings also indicate that a system for
      monitoring the PKC translocation is a powerful tool for investigating the
      subspecies-specific functions of PKCs and mechanism of its translocation.

PMID- 9920198
TI  - A single stranded DNA-binding protein, ssCRE-BP/Pur alpha, in rat lung and its
      increase in allergic airway inflammation.
AB  - ssCRE-BP/Pur alpha is a single stranded DNA-binding protein and may be involved
      in gene replication and transcription and in the development of morphine
      dependence. We found a ssCRE-BP/Pur alpha (45 kDa) in rat lung that was larger
      than those (40 kDa) identified in rat and mouse brains and mouse lung.
      Immunohistochemistry showed that ssCRE-BP/Pur alpha is primarily distributed in
      the lung epithelium. As allergic inflammation induces various gene expressions,
      we investigated the changes of Pur alpha during airway inflammation. Ovalbumin
      sensitized rats were used for inducing allergic airway inflammation. The
      expression and DNA-binding activity of 45-kDa ssCRE-BP/Pur alpha were
      significantly increased in the sensitized rat lungs 24 hr after antigen
      challenge, but not in those of rats nonsensitized or sensitized with ovalbumin
      and challenged with saline. Immunohistochemistry and in situ hybridization
      demonstrated that the vascular endothelial cells and numerous infiltrated
      eosinophils around the airways were stained with anti-Pur alpha antibody. These
      data suggest that rat lung and the eosinophils contain a 45-kDa ssCRE-BP/Pur
      alpha that is increased when airway inflammation occurs.

PMID- 9920199
TI  - Effect of ambroxol on oxygen radical production and generation by bronchoalveolar
      lavage cells in young and aged guinea pigs.
AB  - We examined the effect of ambroxol and age on oxygen radical production and
      generation with stimulation of phorbol-myristate acetate (PMA) by bronchoalveolar
      lavage (BAL) cells. Lung free cells including pulmonary alveolar macrophages were
      harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using
      BAL. The oxygen radicals produced by BAL cells with or without stimulation of PMA
      were measured by the lucigenin-dependent chemiluminescence method using a photon
      counter. Oxygen radical production and generation by BAL cells were not different
      between young and aged guinea pigs. However, the oxygen radical generation after
      stimulation with PMA was greater than the oxygen radical spontaneous production
      both in young and aged animals. Ambroxol solution given into culture media
      containing BAL cells inhibited oxygen radical production and generation by BAL
      cells harvested from both young and aged guinea pigs in a concentration-dependent
      manner. Approximately 16-20 microM of ambroxol inhibited 50% of the production of
      oxygen radicals in vitro by BAL cells in young and aged guinea pigs, whereas a
      slightly greater amount of ambroxol was necessary to inhibit 50% of the PMA
      induced oxygen radical generation in vitro by BAL cells in guinea pigs. These
      results indicate that ambroxol inhibits oxygen radicals produced by BAL cells
      from young and aged guinea pigs, and they suggest that ambroxol may be a possible
      therapeutic modality for ameliorating oxidant associated pulmonary disorders in
      young and aged patients.

PMID- 9920200
TI  - Anti-ulcer effects of antioxidants, quercetin, alpha-tocopherol, nifedipine and
      tetracycline in rats.
AB  - When free radical-scavenging activities of quercetin, alpha-tocopherol,
      nifedipine and tetracycline were measured by an electron spin resonance
      technique, all test compounds (10(-5) to 10(-3) M) scavenged both superoxide
      anions and hydroxyl radicals. The oral administration of quercetin (50 and 100
      mg/kg), alpha-tocopherol (8 and 16 mg/kg), nifedipine (20 and 40 mg/kg) or
      tetracycline (10 and 20 mg/kg) markedly prevented the HCl plus ethanol-induced
      gastric mucosal injury and the increase in the content of thiobarbituric acid
      reactive substances in the injured mucosa in rats. In addition, quercetin (25, 50
      and 100 mg/kg), alpha-tocopherol (4, 8 and 16 mg/kg), nifedipine (10, 20 and 40
      mg/kg) and tetracycline (5, 10 and 20 mg/kg), given orally, twice daily for 14
      consecutive days from the day after acetic acid injection, dose-dependently
      promoted the ulcer healing and inhibited the increase in the content of
      thiobarbituric acid-reactive substances in the ulcerated mucosa. These results
      indicate that quercetin, alpha-tocopherol, nifedipine and tetracycline possess
      gastric cytoprotective and gastric ulcer healing-promoting actions. In addition,
      the free radical-scavenging properties of these compounds may be partly related
      to their anti-ulcer effects.

PMID- 9920202
TI  - Effects of peptidase inhibitors, [D-Ala2, Met5]-enkephalinamide and antiserum to
      methionine-enkephalin microinjected into the caudal periaqueductal gray on
      morphine withdrawal in rats.
AB  - We examined the involvement of enkephalins in the caudal periaqueductal gray
      (cPAG) in morphine withdrawal in rats. Rats were treated with increasing doses of
      morphine (20-30 mg/kg/day, s.c., for 5 days) to develop morphine dependence.
      Morphine withdrawal was induced by naloxone (5 mg/kg, s.c.) 24 hr after the final
      morphine injection. The level of preproenkephalin (PPE) mRNA in the cPAG was
      estimated by quantitative in situ hybridization. PPE mRNA in the cPAG was
      increased 4-24 hr after naloxone in morphine-treated rats. A mixture of peptidase
      inhibitors (0.5 microl of a solution of amastatin, captopril and phosphoramidon,
      3 x 10(-3) M each) microinjected into the cPAG suppressed morphine withdrawal (a
      decrease in the number of jumping, chin rubbing, paw rubbing and teeth
      chattering). Antiserum to methionine-enkephalin (1:10 dilution) microinjected
      into the cPAG did not significantly aggravate morphine withdrawal with or without
      the mixture of peptidase inhibitors. However, [D-Ala2, Met5]-enkephalinamide (20
      nmol), an enkephalin analog, injected into the cPAG decreased the number of
      jumping without any influence on the other withdrawal signs. These results
      suggest that the increase in enkephalins in the cPAG may participate in the
      alleviation of morphine withdrawal (jumping behavior).

PMID- 9920201
TI  - Heroin antinociception changed from mu to delta receptor in streptozotocin
      treated mice.
AB  - CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2
      weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments
      changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given
      intracerebroventricularly from a mu- to delta-opioid receptor-mediated action as
      determined by differential effects of opioid receptor antagonists. The response
      to morphine remained mu. Heroin and 6 MAM responses involved delta1 (inhibited by
      7-benzylidenenaltrexone) and delta2 (inhibited by naltriben) receptors,
      respectively. These delta-agonist actions did not synergize with the mu-agonist
      action of morphine in the diabetic mice. The expected synergism between the delta
      agonist, [D-Pen2-D-Pen5]enkephalin (DPDPE), and morphine was not obtained in
      diabetic mice. Thus, diabetes disrupted the purported mu/delta-coupled response.
      In nondiabetic CD-1 mice, heroin and 6 MAM produced a different mu-receptor
      response (not inhibited by naloxonazine) from that of morphine (inhibited by
      naloxonazine). Also, these mu actions, unlike that of morphine, did not synergize
      with DPDPE. The unique receptor actions and changes produced by streptozotocin
      suggest that extrinsic in addition to genetic factors influence the opioid
      receptor selectivity of heroin and 6 MAM.

PMID- 9920203
TI  - GTS-21, a nicotinic agonist, attenuates multiple infarctions and cognitive
      deficit caused by permanent occlusion of bilateral common carotid arteries in
      rats.
AB  - We examined the effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine
      dihydrochloride], a nicotinic agonist, on histopathological changes of the brain
      and radial maze learning performance in rats with permanent occlusion of the
      bilateral common carotid arteries (2VO) and elucidated whether this compound has
      a protective effect against the neuronal degeneration and spatial cognitive
      deficit caused by chronic ischemia. Rats were administered GTS-21 (1 and 10
      mg/kg, p.o.) or vehicle 24 hr and 30 min before the 2VO operation and then once
      daily for 2 months after the operation. The 2VO rats given vehicle had multiple
      infarctions in the cerebral cortex, hippocampus and striatum and rarefaction in
      the white matter at 2 months after the operation, although the number and
      distribution of infarctions varied among individual animals. In addition, the 2VO
      rats given vehicle showed a higher rate of errors in the acquisition trials of
      the 8-arm radial maze task than sham-operated controls. However, 2VO rats treated
      with GTS-21 (1 and 10 mg/kg, p.o.) showed significantly decreased
      neuropathological changes and less errors in the acquisition trials compared to
      the vehicle-treated 2VO rats. These results indicate that GTS-21 attenuates
      impairment of spatial cognitive deficit and progressive neuronal degeneration
      induced by 2VO and suggest that this compound is beneficial for the treatment of
      neurodegenerative diseases following chronic cerebral hypoperfusion.

PMID- 9920204
TI  - A quantitative assay for angiogenesis of cultured choroidal tissues in
      streptozotocin-diabetic Wistar and spontaneously diabetic GK rats.
AB  - Angiogenesis of cultured choroids was quantitatively assayed in spontaneously
      diabetic GK and a bolus-treated streptozotocin (STZ)-diabetic Wistar rats. The
      number and total length of microvessels budded from cultured choroidal explants
      were measured to use as angiogenic indices. Both indices in 10-week-old Wistar
      rats were increased in parallel by 5% fetal bovine serum (FBS) from days 2 to 7
      in culture. These indices in STZ-rats (10 weeks of age) were increased by 5% FBS
      to a greater extent than those in age-matched normal rats. These enhanced actions
      of FBS were concentration-dependent. The explants of 16-week-old GK rats also
      increased these indices to a greater extent than those of age-matched Wistar
      rats. Aging to 18 weeks of age also increased choroidal angiogenesis in the
      normal rats. In conclusion, the assay model of choroidal angiogenesis was
      established by determining the number and length of microvessels in cultured
      choroidal explants. The diabetic states of STZ-Wistar and GK rats enhanced FBS
      induced choroidal angiogenesis. This assay model is useful for determining
      angiogenic activity of growth factors and effective drugs in diabetic
      choroidopathy and retinopathy.

PMID- 9920205
TI  - Effects of ridogrel, a thromboxane synthase inhibitor and receptor antagonist, on
      blood pressure in the spontaneously hypertensive rat.
AB  - Ridogrel is a dual acting thromboxane synthase inhibitor/TP receptor antagonist.
      We examined the effects of single and multiple doses on systolic blood pressure
      in stroke-prone spontaneously hypertensive rats. Single doses of ridogrel (5 to
      125 mg/kg) did not affect systolic blood pressure or furosemide-stimulated
      excretion rates of thromboxane B2 or 6-keto-prostaglandin F1alpha, although ex
      vivo serum thromboxane B2 was dose-dependently reduced up to 95%. In contrast,
      repeated dosing (7 days) with ridogrel (3 to 25 mg/kg/day), had an
      antihypertensive effect in 12-week-old stroke-prone spontaneously hypertensive
      rats. At 25 mg/kg/day, ridogrel reduced systolic blood pressure from 200+/-6.1 to
      173+/-6.7 mmHg (n=12, P<0.01). Ridogrel dose-dependently reduced serum
      thromboxane B2 and increased plasma renin activity. Unlike single doses, repeated
      dosing reduced urinary thromboxane B2 excretion (from 103+/-7 ng/day to 49+/-10
      ng/day, P<0.01) while preserving 6-keto-prostaglandin F1alpha excretion.
      Ketoprofen, a cyclo-oxygenase inhibitor, (10 mg/kg/day for 7 days), depressed
      urine 6-keto-prostaglandin F1alpha in addition to attenuating serum and urine
      thromboxane B2. Ketoprofen prevented the antihypertensive effects of ridogrel.
      Ridogrel did not lower systolic blood pressure in Sprague-Dawley rats. We
      conclude that the antihypertensive effect of ridogrel involves preserving renal
      prostaglandin synthesis during thromboxane attenuation.

PMID- 9920206
TI  - Effects of peptidase inhibitors on the enkephalin-induced anti-nociception in
      rats.
AB  - The intra-third-ventricular (i.t.v.) administration of [Met5]-enkephalin (enk) to
      rats pretreated i.t.v. with three peptidase inhibitors (PIs), amastatin,
      captopril and phosphoramidon, inhibited the tail-flick response. The enk-induced
      inhibition was augmented by increasing the doses of the three PIs, with the
      maximum inhibition being attained at the doses of 10 nmol each. The enk-induced
      inhibition in rats pretreated with any combination of two PIs, however, were
      markedly smaller than that in rats pretreated with all three PIs, indicating that
      three kinds of enzymes all played important roles in the inactivation of enk. The
      inhibitory effect of enk on the tail-flick response in rats pretreated with the
      three PIs at doses of 10 nmol each was approximately tenfold higher than that of
      morphine. The relative anti-nociceptive potencies of enk and morphine were
      similar to the relative inhibitory potencies obtained previously with the
      isolated guinea pig ileum pretreated with the three PIs, indicating that the
      hydrolysis of the i.t.v. administered enk was largely prevented by the three PIs.
      However, the magnitude of the enk-induced inhibition in rats pretreated s.c. with
      the three PIs indicated that the hydrolysis of enk injected i.t.v. was not
      largely prevented by the s.c. administration of three PIs at doses up to 10
      micromol each/kg.

PMID- 9920207
TI  - Effects of low temperature on the chronotropic and inotropic responses to
      zatebradine, E-4031 and verapamil in isolated perfused dog atria.
AB  - We investigated the effects of hypothermia (25 degrees C) on the chronotropic and
      inotropic effects of zatebradine (a blocker of hyperpolarization-activated inward
      current, I(f)), E-4031 (a blocker of the rapid type of the delayed rectifier K+
      current, I(Kr)) and verapamil, and on the positive cardiac responses to
      isoproterenol after treatment with zatebradine and E-4031 in isolated, blood
      perfused dog atria. Hypothermia shifted the dose-response curves to the right for
      the negative chronotropic and inotropic effects of verapamil and for the negative
      chronotropic and positive inotropic effects of zatebradine, but not for the
      negative chronotropic and positive inotropic effects of E-4031. Hypothermia
      attenuated the positive chronotropic response to isoproterenol or Bay k 8644 (an
      L type Ca2+ channel agonist) and was attenuated more than the inotropic one.
      Zatebradine selectively inhibited the positive chronotropic response to
      isoproterenol at a normal temperature, but in hypothermia, it inhibited neither
      the chronotropic nor inotropic responses. E-4031 did not affect the positive
      responses to isoproterenol. These results suggest that verapamil and zatebradine
      but not E-4031 influence the atrial rate and contractile force much less in
      hypothermia than in normothermia and that the I(f) and inward Ca2+ current are
      sensitive to hypothermia in the heart.

PMID- 9920208
TI  - Catecholaminergic mechanisms-mediated hypothermia induced by magnolol in rats.
AB  - Intraperitoneal administration of magnolol (25-100 mg/kg) produced a dose-related
      fall in rats' colonic temperature. The magnolol-induced hypothermia was
      attenuated by pretreatment with intracerebroventricular 6-hydroxydopamine (200
      microg/rat). The L-DOPA (200 mg/kg, i.p.) plus benserazide (50 mg/kg, i.p.)
      induced hyperthermia was attenuated by magnolol. On the other hand, the alpha
      methyltyrosine (100 mg/kg, i.p.)-induced hypothermia was potentiated by magnolol.
      Furthermore, magnolol (50 mg/kg, i.p.) decreased the dopamine and norepinephrine
      release in the hypothalamus, but did not change the concentrations for their
      metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The data
      suggest that magnolol decreases colonic temperature by reducing catecholaminergic
      activity in rat hypothalamus.

PMID- 9920210
TI  - Serotonin receptor subtypes involved in modulation of electrical acupuncture.
AB  - We examined the effects of intravenous injection of several serotonin (5-HT)
      antagonists on the inhibitory action of electro-acupuncture (EAP) against the
      nociceptive responses in the trigeminal nucleus caudalis in rabbits. The
      inhibitory effect of EAP was suppressed by pindolol, methysergide and ICS 205
      930, whereas NAN-190 and ketanserin amplified the EAP effect. These results
      suggest that 5-HT1, except 5-HT1A; 5-HT2, except 5-HT2A; and 5-HT3 receptors are
      positively involved in EAP-induced analgesia, whereas the activation of 5-HT1A
      and 5-HT2A receptors suppressively act on EAP-induced analgesia.

PMID- 9920209
TI  - Local anti-inflammatory activity and systemic side effects of NM-135, a new
      prodrug glucocorticoid, in an experimental inflammatory rat model.
AB  - The local anti-inflammatory activity and systemic side effects of NM-135
      (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4
      methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton
      oil-induced granuloma pouches and ear edema in rats were studied. The local anti
      inflammatory activity of NM-135 was stronger than that of betamethasone 17
      valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV)
      caused thymolysis at the doses required for the anti-inflammatory activity. In
      contrast, no clear systemic side effect was observed in rats administered NM-135
      at the dose producing the anti-inflammatory activity. These results suggest that
      NM-135 is a drug exhibiting a high degree of dissociation between the local anti
      inflammatory activity and systemic side effects.

PMID- 9920211
TI  - Enhancement of serotonin 2C receptor mRNA expression by antidepressants
      possessing the receptor-blocking activity in the rat brain.
AB  - The effects of repeated oral administration of antidepressants on the serotonin
      2C receptor subtype (5-HT2CR) mRNA level in the rat brain were examined.
      Imipramine (20 mg/kg, p.o.) enhanced the hybridization signal in a time (days)
      dependent manner, reaching a maximum at day 4 and maintaining a high level until
      day 14. Desipramine and mianserin, which have 5-HT2CR antagonistic activity, also
      stimulated the mRNA expression to about same extents as imipramine, but
      nomifensine, which has no effect on 5-HT2CR, was ineffective. These results
      suggest that long-term treatment with antidepressants, which act as 5-HT2CR
      antagonists, stimulates 5-HT2CR mRNA expression.

PMID- 9920212
TI  - Teprenone, an anti-ulcer agent, increases gastric mucosal mucus level via nitric
      oxide in rats.
AB  - We examined whether the increasing action of teprenone (TP) on mucus synthesis
      and content in rat gastric mucosa is related to nitric oxide (NO) formation via
      NO synthase (NOS) in the tissue. TP (200 mg/kg)-induced increases in levels of
      gastric mucosal hexosamine and adherent mucus were inhibited with decreased
      gastric mucosal NOS activity and nitrite/nitrate concentration by co
      administration of NG-monomethyl L-arginine (100 mg/kg), a NOS inhibitor, but not
      its D-isomer. These results suggest that TP exerts an increasing action on
      gastric mucus synthesis and content possibly under the condition of maintained NO
      production via NOS in gastric mucosal tissues, although the precise mechanisms
      for the action of TP is still unclear.

PMID- 9920213
TI  - Higher environmental temperature potentiates cataleptic effect of fentanyl in
      rats.
AB  - The influence of higher environmental temperature (HET=30/-1 degrees C) on
      fentanyl-induced behavior was studied in unrestrained rats. Subacute exposure (3
      days) of rats to HET significantly (P<0.01) increased the cataleptic effect of
      fentanyl citrate (0.5 mg/kg), in comparison to the corresponding exposure to
      normal environmental temperature (NET=22+/-1 degrees C). Also, the hyperthermic
      response of rats to a low dose of fentanyl citrate (0.2-0.5 mg/kg) was
      significantly (P<0.01) potentiated, and the hypothermic response to a high dose
      of fentanyl citrate (1.5 mg/kg) was significantly (P<0.05) attenuated after
      exposure to HET. Fentanyl-induced hyperexcitability, loss of righting reflex,
      loss of corneal reflex and analgesia were not significantly affected by HET. This
      study provides the first evidence on the influence of environmental temperature
      on drug-induced catalepsy. HET-induced potentiation of the cataleptic response to
      fentanyl could be the result of an interference with behavioral thermoregulation.

PMID- 9920214
TI  - Exercise induced asthma in children and adolescents and the relationship to
      sports.

PMID- 9920215
TI  - Prevalence and characteristics of exercise-induced asthma in children.
AB  - We have evaluated the prevalence and the characteristics of exercise-induced
      asthma (EIA) in a group of 71 patients with a prior history of mild, moderate or
      severe asthma (42 males and 29 females), aged 6-16 years-old. Measurements of the
      forced expiratory volume in 1 second (FEV1) were obtained before and at regular
      intervals up to 8 hours following exercise. As a control, the same patients were
      evaluated at similar time intervals on another day when they had not been
      submitted to an exercise challenge. Using pre-exercise FEV1 values as the
      reference, 32 patients (45.1%) had a positive exercise challenge, defined as a
      fall in FEV1 value equal to or greater than 15% from baseline following exercise.
      Among the patients with a positive exercise challenge, the majority (23/32,
      71.8%) had an immediate response alone, with no significant changes in FEV1
      within the 8-hour follow-up. However, a subgroup of patients (9/32, 28.1%) had
      both an immediate and a late-phase response to exercise. During the control day,
      no significant fall in FEV1 were observed. In keeping with previous
      investigations, no correlation was found between a history of EIA and a positive
      exercise challenge in the present study. Positive exercise challenges were found
      more frequently among patients with moderate and severe asthma than patients with
      mild asthma.

PMID- 9920216
TI  - Interpreting skin prick tests in the evaluation of food allergy in children.
AB  - BACKGROUND: Skin prick tests (SPTs) are utilized routinely in the evaluation of
      food allergy and several authors have discussed their utility. Efforts to
      standardize SPT reagents and procedures have been made, but the accuracies of
      different recording techniques have not been clearly defined. The aim of this
      study was to compare different SPT recording methods with the outcome of oral
      food challenge and determine whether they offer any advantage over the criteria
      proposed by Bock and May (1). PATIENTS AND METHODS: Children suspected of IgE
      mediated symptoms to any of five common food allergens (egg, milk, peanut, soy
      and wheat) were skin tested by the prick technique utilizing commercial extracts.
      The wheal reactions were recorded by two different methods: first by measuring
      the largest diameter of the wheal and the diameter orthogonal to it (mean wheal
      diameter), and second by recording the surface area of the wheal with a hand-held
      scanner. Wheal sizes above the 95% confidence interval of tolerant individuals
      were considered positive. The results of double-blind, placebo-controlled food
      challenges were considered the "gold standard" for diagnosis. Cut-off values were
      compared for positive responses in our study population (mean diameter/surface
      area of wheal): 4 mm/16 mm2 for egg, 5 mm/29 mm2 for milk, 6 mm/40 mm2 for
      peanut, 3 mm/9 mm2 for soy, and 3 mm/7 mm2 for wheat. RESULTS: Significant
      differences in wheal sizes were seen between individuals who were allergic or
      tolerant to egg (P < 0.001), milk (P < 0.001), wheat (P < 0.005), and peanut (P <
      0.05). Reactivity to soy could not be predicted based on SPT results (P = n.s.).
      The sensitivities and the specificities of the two recording methods were
      similar. The predictive values were not significantly different from that of the
      commonly utilized method of grading SPTs (i.e. positive = mean diameter 3 mm or
      greater than the negative control). CONCLUSIONS: Skin prick tests are a useful
      procedure for evaluating clinical reactivity to egg, milk, peanut and wheat, but
      not to soy. While the size of the SPT wheals may be interpreted utilizing mean
      diameter or surface area cut-offs, the predictive values of these measurement
      methods were no better than the commonly utilized grading method where a positive
      skin test was recorded as a mean wheal diameter 3 mm greater than the negative
      control.

PMID- 9920217
TI  - Effectiveness of a home-made meat based formula (the Rezza-Cardi diet) as a
      diagnostic tool in children with food-induced atopic dermatitis.
AB  - The aim of this study was to investigate the effectiveness of a home-made meat
      based formula (the Rezza-Cardi diet), as a diagnostic tool for children with
      atopic dermatitis and suspected multiple food hypersensitivity. Severity scores
      for atopic dermatitis, body weight and serum lipid profile were evaluated at
      baseline and four weeks following the feeding with the home-made meat based
      formula in 16 children with atopic dermatitis and suspected multiple food
      hypersensitivity. The severity score of the skin lesions improved considerably in
      all the children; no significant difference was observed in the serum lipid
      levels before and after one month following the feeding with the home-made meat
      based formula. All children gained weight according to the Italian Standards. The
      results of this study indicate that the home-made meat based formula is a useful
      elimination diet in children with atopic dermatitis and suspected multiple food
      hypersensitivity.

PMID- 9920218
TI  - The relationship of serum-eosinophil cationic protein and eosinophil count to
      disease activity in children with bronchial asthma.
AB  - BACKGROUND: The serum-eosinophil cationic protein level (S-ECP) has been promoted
      as a biomarker of asthma that reflects the degree of bronchial eosinophilic
      inflammation. PATIENTS AND METHODS: To investigate whether S-ECP is indeed a
      clinically useful objective parameter, especially in mild or moderate chronic
      childhood asthma, we studied 100 outpatient children with chronic asthma symptoms
      (63 boys and 37 girls, aged three to 15 years, median of age eight) and 25
      controls (12 boys and 13 girls aged three to 15 years, median of age eight).
      Symptom scores, lung function parameters and atopy were compared with S-ECP
      determined by commercially available tests and eosinophils measured by an
      autoanalyser. RESULTS: Asthma symptom scores in the patient group ranged between
      one and 13 (median of 8), S-ECP between 2.1 and 75.6 microg/l (median of 13.3
      microg/ l), and eosinophils between 30/microl and 2002/microl (median of 314).
      Symptom scores and S-ECP were correlated significantly (P < 0.001) as were
      symptom scores and eosinophils (P = 0.001). S-ECPs were significantly higher in
      children with chronic asthma symptoms compared with non-asthmatic, non-atopic
      children (P = 0.005 for non-atopic chronic asthmatics and P < 0.001 for atopic
      asthmatics); similar results were found comparing eosinophils in these groups.
      There was no difference in S-ECP between atopic and non-atopic asthmatic
      children, but the 25 polysensitised asthmatic children especially with
      sensitisations to mite, pollen and pet allergens were found to have significantly
      higher S-ECP compared to 15 monosensitised children (P = 0.002). Similar results
      were found when correlating eosinophil numbers with atopy. Polysensitised (mite,
      pollen, pet) asthmatics had significantly higher eosinophil counts compared with
      monosensitised (pollen) asthmatics (P = 0.01); there was, however, a better
      discrimination between atopic and non-atopic asthmatics (P = 0.001). Non
      asthmatic, non-atopic controls had significantly lower eosinophil counts compared
      with asthmatics (P < 0.001 for both non-atopic and atopic asthmatics). No
      correlation between S-ECP or eosinophils and any of the lung function parameters
      measured (FEV1, FEV1/FVC, MEF50, airway resistance and ITGV) was found. SUMMARY:
      Our data thus indicate that 1) S-ECP is higher than normal in children with
      asthma symptoms and correlates with asthma symptom score. 2) S-ECP is better
      correlated to symptom score than to lung function parameters especially in
      children with mild and moderate asthma symptoms. 3) Raised S-ECP appears to
      reflect the extent of allergen sensitivity and may also reflect current allergen
      exposure. 4) Similar correlations were seen when measuring eosinophil number by
      an autoanalyser instead of S-ECP. CONCLUSIONS: Although S-ECP and eosinophils are
      not diagnostic of asthma they are useful inflammation markers especially in the
      context of clinical studies. However, both methods are not yet suitable for use
      in daily practice because they require extensive procedures and special
      equipment.

PMID- 9920219
TI  - Is serum eosinophil cationic protein in bronchiolitis a predictor of asthma?
AB  - To examine their possible predictive value for the development of asthma, the
      serum concentration of eosinophil cationic protein (ECP) and the total eosinophil
      count were measured at admission in 25 children aged 1-17 months hospitalized for
      their first episode of bronchiolitis. After an average of three years the parents
      of 23 index patients answered a questionnaire to determine development of asthma.
      Eight children were defined as having asthma at follow-up based on at least three
      episodes of wheezing. The remaining 15 children had experienced only one or two
      episodes of wheezing, and all of these children had been wheeze free for the last
      year. The serum concentrations of ECP were similar in children who subsequently
      developed asthma (8.0 microg/l; 3.6 to 14.2 (median; quartiles)) and in those who
      did not (12 microg/l; 4.5 to 16.8). Moreover, the total eosinophil counts were
      similar in asthmatic (0.10 x 10(9)/l; 0.04 to 0.20) and non-asthmatic patients
      (0.09 x 10(9)/l; 0.02 to 0.13). In conclusion, our study suggest that neither the
      serum concentration of ECP nor the total eosinophil count can predict the
      development of asthma when measured in children admitted for their first episode
      of bronchiolitis, but larger studies need to be carried out to confirm these
      results.

PMID- 9920220
TI  - IgG subclass antibody responses to birch pollen in sibling pairs discordant for
      atopy.
AB  - Birch pollen allergen specific IgG and IgE antibodies were analysed in the sera
      of fourteen sibling pairs discordant for atopy. In addition, eight unrelated
      children free of atopic disease were included in the study. The presence of Bet v
      1 specific antibodies in the sera were analysed by an immunoblotting assay. All
      but one (13/14) of the atopic children had detectable anti-Bet v 1 antibodies of
      the IgG1 and IgG4 subclasses. The child lacking IgG1 and IgG4 antibodies to Bet v
      1 was the only allergic child lacking IgE to Bet v 1. In contrast, only one of
      the non-atopic siblings (1/14) displayed detectable IgG1 antibodies to Bet v 1.
      Furthermore, among the non-atopic siblings none (0/14), had detectable IgG4
      antibodies to Bet v 1. In the unrelated control group no detectable IgG1 or IgG4
      anti-Bet v 1 were detected (0/8). Thus of the non-atopic children only one out of
      22 children displayed IgG1 anti-Bet v 1 antibodies. Taken together, it appears
      that the non-atopic children in general have no/low allergen specific IgG to
      birch pollen.

PMID- 9920221
TI  - Age-related changes in blood lymphocyte subsets of Chinese children.
AB  - BACKGROUND: Flow cytometric analysis of major lymphocyte populations and their
      subsets reveals age-related changes in the human cellular immune system. SUBJECTS
      AND METHODS: Immunophenotypic markers were evaluated in 136 healthy pediatric
      subjects divided into groups of newborn infants (cord blood), children aged 1 to
      2 years, 2 to 5 years, and 6 to 15 years. RESULTS: The percentage of T cells
      increased gradually with age and the evolution of the percentage of B and NK
      cells was found to be variable. The percentage of CD4+ cells remains relatively
      unchanged from infancy to adolescence, but the percentage of CD8+ T cells was
      lowest at birth and reached maximal levels in the one to two year-old period. The
      percentage of naive T cells declined with time, but the percentage of memory T
      cells increased with age. Similar trends were seen in T-cell receptor alphabeta-
      and gammadelta-bearing T cells. The percentage of CD 11b+CD8+ T cells increased
      gradually from birth and reached maximal levels from 6 to 15 years old. The
      expression of the activation markers CD25 and HLA-DR on CD4+ T cells increased
      with age. The percentage of CD16+CD56- NK cells declined with age, but the
      evolution of the percentage of CD 16-CD56+ NK cells was variable. The fraction of
      B cells that expressed CD5 was high at birth (72.9%) and was highest in one to
      two year olds (73.1%), then declined steadily over time. The CD23 antigen was
      expressed on 41.9% of B cells at birth and 68.6% during the first to second year,
      then declined steadily with age. CONCLUSION: These data may serve as a reference
      range for studies of Chinese pediatric subjects.

PMID- 9920222
TI  - Mailed reminders for area-wide influenza immunization: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine if mailed reminders would increase area-wide influenza
      immunization for persons aged 65 and older. DESIGN: A randomized, controlled
      trial. SETTING: Ten counties in Indiana. PARTICIPANTS: Using a Medicare database,
      10,000 subjects were selected randomly from 10 counties in Indiana and randomized
      for the study. Using pre-established criteria, 4503 persons in the control group
      and 4508 in the intervention group were eligible for study. INTERVENTION:
      Intervention subjects received mailed reminders during the immunization season of
      1995. MEASUREMENTS: Data from mailed surveys, Medicare claims, and phone calls
      were used to determine immunization rates. RESULTS: Of those surveyed who
      received immunization, only 63.4% filed a Medicare claim. Immunization rates were
      high in both groups but higher in the intervention group, 69.0% versus 64.2%.
      Age, presence of lung disease, assignment to the intervention group, presence of
      heart disease, and an age-sex interaction term were significantly and
      independently related to immunization. CONCLUSIONS: The Healthy People Year 2000
      goal (60% immunization for persons 65 and older) was exceeded in this population.
      Medicare claims data do not reflect immunization rates accurately. Mailed
      reminders, an inexpensive intervention, increased immunization rates area-wide
      and have potential for cost savings.

PMID- 9920223
TI  - Association of interleukin-6 and other biologic variables with depression in
      older people living in the community.
AB  - OBJECTIVES: The prevalence of depression increases with age, as does the
      prevalence of higher levels of the cytokine interleukin-6 (IL-6). This analysis
      was performed to determine the association between increased levels of this
      cytokine and depression in a population-based sample. DESIGN: Cross-sectional
      cohort study. SETTING: Rural and urban counties in North Carolina. PARTICIPANTS:
      Community-dwelling older people. MEASUREMENTS: The association between IL-6 and
      other biologic variables with self-report depression was examined in 1686 persons
      aged 70 years and older in the third in-person survey wave (1991) of the Duke
      Established Population for Epidemiologic Studies of the Elderly (EPESE).
      Bivariate associations were established by the Spearman correlation, adjusted for
      age. A stepwise linear logistic regression model was used to derive a final model
      to assess multivariable effects on CES-D scores. RESULTS: Depression was
      correlated with IL-6 (P = .011), D-Dimer (P = .017), alpha-1-globulin (P = .023),
      alpha-2-globulin (P = .002), and beta globulin (P = .012). After controlling for
      age, race, and gender, IL-6 levels remained the only biologic variable
      significantly associated with depression (P = .035). CONCLUSION: These data
      suggest that the inflammatory marker, IL-6, is associated with depression in
      older people in this cross-sectional study. These results are compatible with the
      hypothesis of cytokine (IL-6) stimulation in geriatric depression as part of an
      overall immunoendocrine dysregulation.

PMID- 9920224
TI  - Diagnosis of geriatric patients with severe dizziness.
AB  - OBJECTIVE: To identify the causes of dizziness in older patients presenting to
      the general practitioner and the clinical characteristics at presentation that
      might guide the general practitioner to the likely cause of dizziness and the
      most appropriate specialty for subsequent referral if referral is required.
      DESIGN: A prospective case control study of older patients presenting with
      dizziness. SETTING: The initial assessment was made in four general practices,
      three urban practices and one inner city practice (Newcastle). Subsequent
      investigations were conducted randomly in the Neurocardiovascular Investigation
      Unit and the Otolaryngology (ENT) Unit at local University hospitals (Newcastle).
      PARTICIPANTS: Fifty consecutive patients more than 60 years of age presented with
      dizziness. Twenty-two age- and sex-matched case controls were recruited from the
      same general practices. MEASUREMENTS: Measurements were of diagnoses attributable
      to symptoms. RESULTS: Symptoms were of long duration (median 1 year). Forty-six
      percent of patients had syncope and/or falls in addition to dizziness. Twenty
      eight percent had a cardiovascular diagnosis, 18% had a peripheral vestibular
      disorder, 14% had a central neurological disorder, 18% had more than one
      diagnosis, and 22% had no attributable cause of symptoms identified. A
      cardiovascular diagnosis was predicted by the presence of syncope (P < .001),
      dizziness described as lightheadedness (P < .001), the need to sit or lie down
      during symptoms (P < .001), pallor with symptoms (P < .001), symptom
      precipitation by prolonged standing (P < .05), and whether patients had
      coexisting cardiovascular disease (P < .05). The description of dizziness as
      "vertigo" predicted a peripheral vestibular disorder (P < .001). The predictive
      strength of these prognostic indicators was then validated on a separate sample
      of 50 additional older patients. CONCLUSIONS: Clinical characteristics can
      predict an attributable cause of dizziness in most older patients and thus guide
      general practitioners in treatment and appropriate specialist referral. The
      presence of syncope, falls, or cardiovascular comorbidity increases the
      likelihood of a cardiovascular diagnosis. Otolaryngological investigations are
      rarely diagnostic, but vertiginous symptoms do predict peripheral vestibular
      disorders.

PMID- 9920225
TI  - Long-term functional outcome after intensive care.
AB  - OBJECTIVE: Although age-related mortality after intensive care unit (ICU)
      admission has been studied, functional recovery for different age groups
      following ICU admission is not well characterized. We hypothesized that compared
      with younger age groups, fewer patients older than age 65 admitted to an ICU
      would regain their full prehospitalization functional ability and that their
      recovery would be slower than that of younger patients. DESIGN: A prospective
      observational cohort study with convenience sampling. SETTING: Intensive care
      units of an urban university-affiliated Veterans Administration Medical Center.
      PARTICIPANTS: A total of 222 patients during the first 72 hours after entry to a
      medical or surgical ICU at the Denver Veteran's Administration Medical Center
      between September 1991 and July 1992. MEASUREMENTS: We collected baseline data on
      patient demographics and on the severity of acute illness using the Acute
      Physiology and Chronic Health Evaluation (APACHE II), Acute Physiology Score
      (APS), and functional status (highest level of physical activity level 1 month
      before admission). We recorded survival and patient-perceived global functional
      status at 6 weeks and 6 months after admission. Post-ICU function was adjusted
      for baseline function, age, APACHE II, and APS using multiple regression.
      RESULTS: Average patient age was 62+/-.74 years (mean +/- SEM). Fifty-two percent
      of the entire cohort returned to baseline function at 6 months. Although baseline
      function was better for younger people, there was no difference in recovery at 6
      weeks in older compared with younger patients. Most functional recovery occurred
      by 6 weeks, with maintenance of this recovery at 6 months. Baseline function was
      the major determinant of both 6 week recovery (P < .001) and 6 month recovery (P
      = .002), whereas APACHE II was not (P = .3). Age predicted recovery significantly
      (P = .04) at 6 months but not at 6 weeks (P = .26). APACHE II (P < .001) and
      baseline function (P = .03) predicted mortality. CONCLUSIONS: Older people had
      worse functional ability at ICU admission, but the proportion of older people who
      recovered and their rate of recovery was the same as for younger people. Baseline
      functional status, rather than abnormal physiologic status (as measured by APACHE
      II) on admission, was the major determinant of recovery, whereas APACHE II was
      the main correlate of mortality. Together, baseline function and physiologic
      status provide valuable complementary information for clinically relevant
      outcomes following an ICU admission.

PMID- 9920226
TI  - Who dies at home? Determinants of site of death for community-based long-term
      care patients.
AB  - OBJECTIVE: To determine characteristics associated with site of death in a cohort
      of long-term homecare patients. DESIGN: Cohort study. SETTING: Community-based
      long-term care program. SUBJECTS: All patients 65 years of age or older who died
      within 1 year of admission during 1989 and 1990. MAIN OUTCOME MEASURE: Site of
      death. RESULTS: Of 620 subjects, site of death was hospital for 302 (49%), home
      for 132 (21%), nursing home for 124 (20%), and inpatient hospice for 45 (7%).
      Among patients living at home before death, factors associated with dying at home
      rather than in a hospital or inpatient hospice included female gender (relative
      risk (RR) 1.40, 95% confidence interval (CI) 1.00, 1.90); severely dependent
      functional status (RR 2.38, CI 1.39, 4.17) and cognitive status (RR 1.51, CI
      1.10, 2.06); and dying of cancer (RR 1.68, CI 1.11, 2.55), chronic lung disease
      (AOR 1.75, CI 1.04, 2.95), or coronary artery disease (RR 1.93, CI 1.21, 3.09).
      Living with a child (RR 1.45, CI .99, 2.11) showed a trend toward association
      with dying at home. CONCLUSIONS: Even among a subgroup of older persons receiving
      community-based long-term care, the frequency of home death is low. The finding
      of an association between functional, social, and disease status and site of
      death suggests that the relationship between these factors and patients'
      preferences and care needs must be examined in order to understand how to
      optimize the site of terminal care.

PMID- 9920227
TI  - Drugs and falls in older people: a systematic review and meta-analysis: I.
      Psychotropic drugs.
AB  - OBJECTIVES: To evaluate critically the evidence linking psychotropic drugs with
      falls in older people. DESIGN: Fixed-effects meta-analysis. DATA SOURCES: English
      language articles in MEDLINE (1966 - March 1996) indexed under accidents or
      accidental falls and aged or age factors; bibliographies of retrieved papers.
      STUDY SELECTION: Systematic evaluation of sedative/hypnotic, antidepressant, or
      neuroleptic use with falling in people aged 60 and older. DATA EXTRACTION: Study
      design, inclusion and exclusion criteria, setting, sample size, response rate,
      mean age, method of medication verification and fall assessment, fall definition,
      and the number of fallers and non-fallers taking specific classes of psychotropic
      drugs. RESULTS: Forty studies, none randomized controlled trials, met eligibility
      criteria. For one or more falls, the pooled odds ratio (95% confidence interval)
      was 1.73 (95%CI, 1.52-1.97) for any psychotropic use; 1.50 (95%CI, 1.25-1.79) for
      neuroleptic use; 1.54 (95%CI, 1.40-1.70) for sedative/hypnotic use; 1.66 (95%CI,
      1.4-1.95) for any antidepressant use (mainly TCAs); 1.51 (95%CI, 1.14-2.00) for
      only TCA use; and 1.48 (95%CI, 1.23-1.77) for benzodiazepine use, with no
      difference between short and long acting benzodiazepines. For neuroleptics in
      psychiatric inpatients, the pooled OR was 0.41 (95%CI, 0.21-.82); for all other
      patients, the pooled OR was 1.66 (95%CI, 1.38-2.00). Comparing > or =1 with > or
      = 2 falls, mean subject age <75 versus > or =75 years old, communities with <35%
      versus > or =35% fallers, or subject place of residence did not affect the pooled
      OR. Increased falls occurred in patients taking more than one psychotropic drug.
      CONCLUSION: There is a small, but consistent, association between the use of most
      classes of psychotropic drugs and falls. The evidence to date, however, is based
      solely on observational data, with minimal adjustment for confounders, dosage, or
      duration of therapy. The incidence of falls and their consequences in this
      population necessitate that future large randomized controlled trials of any
      medication in older persons should measure falls prospectively as an adverse
      outcome event.

PMID- 9920228
TI  - Drugs and falls in older people: a systematic review and meta-analysis: II.
      Cardiac and analgesic drugs.
AB  - OBJECTIVES: To evaluate critically the evidence linking specific classes of
      cardiac and analgesic drugs to falls in older people. DESIGN: Fixed-effects meta
      analysis. DATA SOURCES: English-language articles in MEDLINE (1966 - March 1996)
      indexed under accidents or accidental falls and aged or age factors;
      bibliographies of retrieved papers. STUDY SELECTION: Systematic evaluation of
      cardiac or analgesic drug use and any fall in people aged 60 years and older.
      DATA EXTRACTION: Study design, inclusion and exclusion criteria, setting, sample
      size, response rate, mean age, method of medication verification and fall
      assessment, fall definition, and the number of fallers and nonfallers taking
      specific classes of cardiac and analgesic drugs. RESULTS: Twenty nine studies met
      inclusion criteria. None were randomized controlled trials. For one or more
      falls, the pooled Odds Ratio (95% Confidence Interval) was 1.08 (1.02-1.16) for
      diuretic use, 1.06 (0.97-1.16) for thiazide diuretics, 0.90 (0.73-1.12) for loop
      diuretics, 0.93 (0.77-1.11) for beta-blockers, 1.16 (0.87-1.55) for centrally
      acting antihypertensives, 1.20 (0.92-1.58) for ACE inhibitors, 0.94 (0.77-1.14)
      for calcium channel blockers, 1.13 (0.95-1.36) for nitrates, 1.59 (1.02-2.48) for
      type Ia antiarrhythmics, and 1.22 (1.05-1.42) for digoxin use. For analgesic
      drugs, the pooled OR was 0.97 (0.78-1.20) for narcotic use, 1.09 (0.88-1.34) for
      nonnarcotic analgesic use, 1.16 (0.97-1.38) for NSAID use, and 1.12 (0.80-1.57)
      for aspirin use. There was no statistically significant heterogeneity of pooled
      odds ratios. There were no differences between the pooled odds ratios for studies
      with mean subject age <75 versus > or =75 years old or for studies in communities
      with <35% versus > or =35% fallers. In studies of the relationship between
      psychotropic, cardiac, or analgesic drugs and falls, subjects reporting the use
      of more than three or four medications of any type were at increased risk of
      recurrent falls. CONCLUSION: Digoxin, type IA antiarrhythmic, and diuretic use
      are associated weakly with falls in older adults. No association was found for
      the other classes of cardiac or analgesic drugs examined. The evidence to date,
      however, is based solely on observational data, with minimal adjustment for
      confounders, dosage, or duration of therapy. Older adults taking more than three
      or four medications were at increased risk of recurrent falls. As a result of the
      incidence of falls and their consequences in this population, programs designed
      to decrease medication use should be evaluated for their impact on fall rates.

PMID- 9920229
TI  - Mortality, health services use, and health behavior in a cohort of well older
      adults.
AB  - OBJECTIVES: To construct an evidence-based Good Health Behavior Score and examine
      the relationship between aggregate health behaviors, mortality, and health
      services utilization in the last year of life in a cohort of well older adults.
      DESIGN: A prospective cohort. SETTING: A large health maintenance organization.
      PARTICIPANTS: 1867 older enrollees who responded to a health promotion survey.
      MEASUREMENTS: A baseline self-administered questionnaire was used to ascertain
      health behaviors in 1987-1988, and vital status was determined 48 months later. A
      Good Health Behavior Score was calculated, and a Cox proportional hazards model
      was used to compare high, middle, and low score groups regarding risk of death.
      For those who died, differences in amount and type of health services utilization
      in relation to the summary score were compared for the year before death.
      RESULTS: During the 4 years of follow-up, the mortality rate for the mid-level
      score group was 50% less, and in the highest score group was 70% less, than in
      the lowest score group. Among decedents, no significant differences were found
      between high and low Good Health Behavior score groups for inpatient and
      outpatient utilization, pharmacy use, or total cost during the last year of life.
      CONCLUSION: An easily developed and simple health behavior score can predict
      short term mortality quite strongly. Medical care costs in the last year of life
      were similar in individuals with higher and lower health behavior scores.

PMID- 9920230
TI  - Is experience as a prisoner of war a risk factor for accelerated age-related
      illness and disability?
AB  - OBJECTIVE: To determine whether the experience of internment as a Prisoner of War
      (POW) during World War II was associated with a higher prevalence of chronic
      disease and diminished functional performance in later life. DESIGN: A
      retrospective and prospective cohort design. SETTING: Concord Repatriation
      General Hospital, Sydney, Australia. PARTICIPANTS: A random sample of 101
      Australian, male, ex-prisoners of the Japanese and a comparison group of 107 non
      POW combatants from the same theatre of war. MEASUREMENTS: Outcome variables were
      self-perceived health status, hospital admissions and length of stay, number of
      prescription medications used, number of somatic symptoms reported, number and
      types of medical diagnoses, a neurology of aging clinical examination, and the
      Instrumental Activities of Daily Living (IADL) and Physical Self Maintenance
      Scales (PSMS). RESULTS: Prisoners of War reported more somatic symptoms (mean 7.2
      vs 5.4, P = .002) than non-POWs, had more diagnoses (mean 9.4 vs 7.7 P < .001),
      and used a greater number of different medications (mean 4.5 vs 3.4, P = .001).
      There were no differences in hospital admissions or length of stay. Among 15
      broad categories of diagnosis, differences were confined to gastrointestinal
      disorders (POWs 63% vs non-POWs 49%, P = .032), musculoskeletal disorders (POWs
      76% vs non-POWs 60%, P = .011), and cognitive disorders (excluding head injury,
      dementia, and stroke) (POWs 31% vs non-POWs 15%, P = .006). Of the 36 signs in
      the neurology of aging examination, POWs had a significantly higher proportion of
      seven extrapyramidal signs and six signs relating to ataxia. POWs were more
      likely to be impaired on the IADL scale than were non-POWs (33% vs 17%, P = .012)
      but not significantly more likely to be impaired on the PSMS. CONCLUSIONS: There
      were few differences between POWs and controls, and those differences were
      relatively small. Our findings do not support a major role for a catastrophic
      life stress in the development of chronic illness and disability in later life.
      However it is possible that the POW experience played a part in premature,
      abnormal, or unsuccessful aging in some individuals.

PMID- 9920231
TI  - Vaginal estrogen creams: use patterns among a cohort of women.
AB  - OBJECTIVE: To assess the prevalence, amount, and duration of use of vaginal
      estrogen cream among several birth cohorts of women from 1983 through 1992.
      DESIGN: Analyses are based on automated membership, pharmacy, and hospital
      discharge databases from Group Health Cooperative (GHC) of Puget Sound, a large
      health maintenance organization in Seattle, Washington. PARTICIPANTS: A total of
      33,822 women, aged 45 years and older as of December 31, 1983, who were enrolled
      in GHC from 1983 to 1992 or who were enrolled at baseline and died in the
      following decade. RESULTS: About 24% of the cohort had filled at least one
      prescription for vaginal estrogen cream during 1983 through 1992, and about 60%
      of the users had more than one prescription filled. The annual birth cohort
      specific prevalence of having filled one or more prescriptions for vaginal
      estrogen creams ranged between 1.6 and 8.2% across birth cohorts, whereas the
      average annual prevalence for the cohort was between 5.3 and 6.8%. The total
      amount, duration of use, and proportion of total estrogen exposure from creams
      increased with age of the birth cohort. Among the 733 women with intact uteri who
      were long-term cream users, 60.4% had no progestin prescriptions while averaging
      22.1 tubes of estrogen cream. CONCLUSION: The prescription-filling patterns for
      estrogen in this cohort show an increase in the amount, years of use, and
      proportion of estrogen exposure from creams with the age of the birth cohort and
      extensive unopposed cream use among a small proportion of women with intact
      uteri. The systemic effects of vaginal estrogen cream among older postmenopausal
      women with urogenital atrophy deserve closer scrutiny.

PMID- 9920232
TI  - Barriers to effective communication in skilled nursing facilities: differences in
      perception between nurses and physicians.
AB  - BACKGROUND: Effective communication between nurses and physicians is central to
      the clinical care of nursing home residents. Anecdotal evidence suggests that
      communication between the groups is unsatisfactory, but no empirical data exist
      with which to validate assumptions. The purpose of this pilot study was to
      compare perceptions of potential communication barriers among nurses and
      physicians in four California nursing homes. METHODS: Registered nurses (n = 59),
      and physicians (n = 47) involved in the direct clinical care of nursing home
      residents completed a 12-item questionnaire designed to elicit perceptions about
      potential communication barriers. Five specific categories of barriers were
      identified. These included nurse competence, time burden of calls, necessity of
      calls, professional respect, and language comprehension. Responses were compared
      using t test analysis. RESULTS: Significant differences in perceived
      communication barriers were identified. Physicians, but not nurses, perceive
      nursing competence to be a significant barrier. Nurses perceive physicians to be
      unpleasant. Both physicians and nurses perceive that physicians do not value
      nurses' opinions. Neither group perceived language expression, language
      comprehension, or time burden of phone calls to be barriers to communication.
      CONCLUSIONS: Issues related to the perceived competency of nurses by physicians
      is consistent with existing data from other clinical settings. Differences in
      awareness about scope of practice and regulatory requirements between the groups
      may offer a partial explanation for the discordant perceptions. Perceptions by
      nurses (but not physicians) of unpleasantness and/or disrespect during telephone
      encounters may reflect the broader ongoing differences in professional culture,
      social status, and gender inequality between the two groups. Further
      clarification of the causes of barriers to effective communication is essential
      in order to plan appropriate interventions.

PMID- 9920233
TI  - What is the quality of the reporting of research ethics in publications of
      nursing home research?
AB  - OBJECTIVE: To assess the quality of reporting of research ethics in published
      clinical research that involves a particularly vulnerable population: nursing
      home residents. DESIGN: A structured review of publications researched from 1992
      to 1996 that involve nursing home residents. The review instrument assessed each
      publication's compliance with four common standards for research that involves
      nursing home residents or the cognitively impaired: justification of the use of
      nursing home residents, Institutional Review Board (IRB) review, nursing home
      committee review, and informed consent. For each publication, these results were
      summed into a quality score. The research ethics requirements contained in the
      journals' instructions for authors that corresponded with each publication were
      categorized in order to compare whether an association exists between the average
      quality score for each category and the detail of its research ethics
      instructions. RESULTS: Forty-five publications were identified. The four quality
      measures of research ethics showed that (1) all 45 publications reported
      justification of use of nursing home residents, (2) 36 publications reported that
      informed consent was obtained or waived, (3) 18 publications reported IRB review,
      and (4) six publications reported nursing home committee review. Of the 35
      publications reporting informed consent was obtained, 16 reported assessing
      subjects' decisional capacity, and 24 reported whether cognitively impaired
      subjects were included (19) or excluded (5). The research ethics requirements of
      each publication's instructions for authors ranked it in one of four categories:
      (A) None (9); (B) Less than "Uniform Requirements (UR) for Manuscripts Submitted
      to Biomedical Journals" (7); (C) UR (24); (D) UR plus Additional Instructions
      (5). A positive association exists between the detail of a research ethics
      instructions category and the average research ethics quality score for each
      category (Kruskal-Wallis chi2 = 11.2, P = .01). That is, the more detailed the
      instructions, the greater the quality score. CONCLUSION: In publications of
      research that involves nursing home residents, basic standards of research ethics
      are not typically reported. However, the positive association between research
      ethics instructions category and research ethics quality score suggests that a
      journal's instructions for authors or other features of peer review and editing
      can affect the quality of reporting research ethics.

PMID- 9920234
TI  - Life-sustaining treatment decisions for nursing home residents: who discusses,
      who decides and what is decided?
AB  - OBJECTIVE: To evaluate whether nursing home residents and their families reported
      discussions about life-sustaining treatment with their physicians, the
      relationship between such discussions and orders to limit therapy, and predictors
      of physician-patient communication about life-sustaining treatment. DESIGN: Cross
      sectional interviews and retrospective chart abstraction. SETTING: Three regions:
      West Coast, New England, Western. SAMPLE: A total of 413 nursing home residents,
      363 family/surrogate interviews, and 192 resident interviews. MAIN OUTCOME
      MEASURES: Measured were (1) physician-resident communication about life
      sustaining treatment and (2) presence of an advance directive or do not
      resuscitate (DNR) order in resident's chart. RESULTS: Seventy-four percent of
      residents had DNR orders, and 32% had advance directives; only 29% of residents
      reported discussions about life-sustaining treatment. Of residents with DNR
      orders who could have participated in discussions about life-sustaining
      treatment, nearly half reported they had not discussed CPR with their caregivers.
      Older age, longer duration of time living in nursing home, location in a New
      England nursing home, physician-family member discussion, and the presence of an
      advance directive in the medical chart were positively associated with having DNR
      orders. Physician-resident discussion was not associated with having a DNR order.
      For the subsample of interviewed residents, age and a diagnosis of cognitive
      impairment were negatively associated with a physician-resident discussion about
      life-sustaining treatment, whereas the likelihood of having a discussion
      increased with increasing numbers of medical diagnoses. CONCLUSIONS: Chart orders
      to limit therapy are common, but physician-resident discussions about life
      sustaining treatments are not. Far more family members than residents report such
      discussions with the resident's physicians.

PMID- 9920236
TI  - Subcutaneous infusion or hypodermoclysis: a practical approach.

PMID- 9920235
TI  - Mismatches between the home environment and physical capabilities among community
      living older persons.
AB  - OBJECTIVE: To determine whether environmental hazards related to transfers,
      balance, and gait are any less prevalent in the homes of older persons with
      specific deficits in physical capabilities than they are in the homes of older
      persons without the same deficits. DESIGN: Cross-sectional study of a population
      based cohort. SETTING: The general community in New Haven, Connecticut.
      PARTICIPANTS: A total of 1088 persons, aged 72 years and older, who had an
      environmental assessment of their homes. MEASUREMENTS: Each participant underwent
      a physical performance assessment and comprehensive interview to document the
      presence of underlying deficits in physical capabilities. Items from the
      environmental assessment that were potentially hazardous for participants with
      specific deficits in transfers, balance, or gait were identified. RESULTS: With
      the exception of no grab bars in the tub/shower, environmental hazards were as
      prevalent in the homes of participants with specific deficits in physical
      capabilities as they were in the homes of participants without the same deficits,
      and, in many cases, they were actually more prevalent. Among participants with
      and without observed difficulty standing from a chair, for example, the
      prevalence of a low lying chair was 24% versus 14% (chi2 = 13.4; P < .001),
      respectively. Among participants with and without an observed deficit in turning,
      the prevalence of an obstructed pathway was 47% versus 37% (chi2 = 8.7; P =
      .003), respectively; and the prevalence of loose throw rugs was 72% in both
      groups. CONCLUSIONS: If the epidemiologic link between environmental hazards and
      adverse functional outcomes can be strengthened, then interventions designed to
      enhance the everyday function of frail, older persons should focus on the
      environment as well as the individual.

PMID- 9920237
TI  - Cardiac rehabilitation in older coronary patients.
AB  - The majority of patients presenting with acute coronary disease or undergoing
      coronary revascularization procedures are older than age 65. Disability rates are
      very high in these patient populations, particularly in women, the older-old, and
      patients with clinical manifestations of angina pectoris or chronic heart
      failure. The presence of mental depression is also an important determinant of
      poor physical functioning. Cardiac rehabilitation has been demonstrated to safely
      increase aerobic capacity, muscular strength, and endurance in older coronary
      populations.

PMID- 9920238
TI  - A managed care organization's attempt to increase influenza and pneumococcal
      immunizations for older adults in an acute care setting.
AB  - OBJECTIVE: Among the high risk groups for complications from influenza and
      pneumococcal disease, individuals aged 65 and older hospitalized within the
      previous year represent the group at highest risk. Studies have demonstrated that
      targeting hospitalized patients aged 65 and older for immunization before
      hospital discharge can be successful. This study addressed the efficacy of such a
      program within a managed care organization to immunize this highest risk group.
      DESIGN: A cross-sectional study. SETTING: Oxford Health Plans, a major managed
      care organization in New York serving a large Medicare population. PARTICIPANTS:
      A total of 106 Primary Care Physicians caring for 153 patients aged 65 and older,
      who were hospitalized in one of 10 high volume hospitals during October and
      November of 1996. Nine of these facilities were located in New York and one was
      in New Jersey. INTERVENTION: Patients aged 65 and older admitted to any of the 10
      hospitals were identified daily. A fax was sent to each patient's primary care
      physician explaining the program and requesting that he/she administer influenza
      and/or pneumococcal vaccine to his/her patient before hospital discharge.
      Literature references citing past successful programs were included in the fax.
      MEASUREMENTS: Measurements included medical record documentation of influenza and
      pneumococcal immunization, both ordered and given, for the individual member
      before discharge; patient age; sex; and primary and secondary diagnoses.
      Physicians were sent follow-up questionnaires to determine reasons for not
      vaccinating. RESULTS: A total of 206 patients were admitted during the eligible
      time period. One hundred fifty-three hospitalized patients (average age = 74
      years) participated. The median length of stay among this study population was 5
      days (range, 1-63 days). The distribution of the median length of stay for the
      25th and 75th percentiles was 3 and 9 days. The rate for influenza and
      pneumococcal immunization, both ordered and given, before hospital discharge was
      1.96% for the influenza vaccine (n = 3) and .65% for the pneumococcal vaccine (n
      = 1), respectively. Results of a follow-up survey mailed to all physicians (n =
      106) with eligible members in the study indicated that the most frequent reasons
      for not vaccinating included: patients were vaccinated before admission, patients
      were not stable enough to be vaccinated before discharge, and the acute care
      setting is not appropriate for vaccination. Response rate of 58% (n = 61) was
      achieved with an initial mailing and one follow-up telephone call to all previous
      nonresponders. Some physician survey responses do not correlate with data
      obtained from retrospective patients' claims analysis. CONCLUSION: Well
      coordinated and timely attempts to encourage primary care physicians to immunize
      patients 65 years and older before hospital discharge were unsuccessful in our
      study. Rather than working with physicians, it may be that managed care
      organizations should work directly with hospitals to implement influenza and
      pneumococcal immunization programs.

PMID- 9920239
TI  - The importance of including the home environment in assessment of frail older
      persons.

PMID- 9920240
TI  - Clinical research and geriatric dizziness: the blind men and the elephant.

PMID- 9920241
TI  - JAGS, Volume One, 1953.

PMID- 9920242
TI  - On managing chronic pain in older persons.

PMID- 9920243
TI  - Aspirin therapy.

PMID- 9920244
TI  - Dementia with Lewy bodies.

PMID- 9920245
TI  - Update: Preventive medicine and screening in older adults.

PMID- 9920246
TI  - Much more than elegant.

PMID- 9920247
TI  - Intellectual property and the parsing of protein space.

PMID- 9920248
TI  - Resolving contradictory reports on cell aging.

PMID- 9920249
TI  - Mycoplasmas as gene therapy vectors?

PMID- 9920250
TI  - Stem cell hearing stirs bioethics debate.

PMID- 9920251
TI  - Battle lines redrawn in BTWC debate. Biological and Toxin Weapons Convention.

PMID- 9920252
TI  - Code alone can't stop misconduct.

PMID- 9920253
TI  - TBA's structure and focus confuse investors. Thermo BioAnalysis.

PMID- 9920255
TI  - Should platform companies move toward products?

PMID- 9920256
TI  - Billion-dollar market blossoms as botanicals take root.

PMID- 9920254
TI  - Fallout from the merger that might be.

PMID- 9920257
TI  - The state of grace.

PMID- 9920258
TI  - Infection, inflammation, and cancer.

PMID- 9920259
TI  - Hope for the post-antibiotic era?

PMID- 9920260
TI  - Longer is better--random elongation mutagenesis.

PMID- 9920261
TI  - Tuning up crop photosynthesis.

PMID- 9920262
TI  - In search of the tabula rasa of human cells.

PMID- 9920263
TI  - Transgene vectors go retro.

PMID- 9920264
TI  - Making forest biotechnology a commercial reality. Do we need a tree genome
      project, or will Arabidopsis point the way?

PMID- 9920265
TI  - Strategies for bioengineering the development and metabolism of glandular tissues
      in plants.
AB  - Glandular tissues in plants produce a wide variety of commercially important
      chemicals. We review specific model systems that can be exploited for
      bioengineering the development and metabolism of these specialized structures,
      and the economic considerations that must be satisfied to permit commercially
      viable bioengineering approaches to specific chemicals and that constrain the
      choice of production systems.

PMID- 9920266
TI  - Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain
      tumor-targeting in vivo.
AB  - Systemically administered tumor-targeted Salmonella has been developed as an
      anticancer agent, although its use could be limited by the potential induction of
      tumor necrosis factor alpha (TNFalpha)-mediated septic shock stimulated by lipid
      A. Genetic modifications of tumor-targeting Salmonella that alter lipid A and
      increase safety must, however, retain the useful properties of this bacteria. We
      report here that disruption of the Salmonella msbB gene reduces TNFalpha
      induction and increases the LD50 of this pathogenic bacteria by 10,000-fold.
      Notwithstanding this enormous difference, Salmonella retains its tumor-targeting
      properties, exhibiting tumor accumulation ratios in excess of 1000:1 compared
      with normal tissues. Administration of this bacteria to mice bearing melanoma
      results in tumors that are less than 6% the size of tumors in untreated controls
      at day 18. Thus, the antitumor activity previously demonstrated using tumor
      targeting Salmonella with normal lipid A is retained. Lipid modification of tumor
      specific bacterial vectors provides a means for reducing septic shock and further
      suggests that the antitumor activity of these bacteria may be independent of
      TNFalpha.

PMID- 9920267
TI  - A synthetic peptide adhesion epitope as a novel antimicrobial agent.
AB  - The earliest step in microbial infection is adherence by specific microbial
      adhesins to the mucosa of the oro-intestinal, nasorespiratory, or genitourinary
      tract. We inhibited binding of a cell surface adhesin of Streptococcus mutans to
      salivary receptors in vitro, as measured by surface plasmon resonance, using a
      synthetic peptide (p1025) corresponding to residues 1025-1044 of the adhesin. Two
      residues within p1025 that contribute to binding (Q1025, E1037) were identified
      by site-directed mutagenesis. In an in vivo human streptococcal adhesion model,
      direct application of p1025 to the teeth prevented recolonization of S. mutans
      but not Actinomyces, as compared with a control peptide or saline. This novel
      antimicrobial strategy, applying competitive peptide inhibitors of adhesion, may
      be used against other microorganisms in which adhesins mediate colonization of
      mucosal surfaces.

PMID- 9920268
TI  - Cellular penetration and antisense activity by a phenoxazine-substituted
      heptanucleotide.
AB  - One of the major barriers to the development of antisense therapeutics has been
      their poor bioavailability. Numerous oligonucleotide modifications have been
      synthesized and evaluated for enhanced cellular permeation with limited success.
      Phenoxazine, a tricyclic 2' deoxycytidine analog, was designed to improve
      stacking interactions between heterocycles of oligonucleotide/RNA hybrids and to
      enhance cellular uptake. However, the bioactivity and cellular permeation
      properties of phenoxazine-modified oligonucleotides were unknown. Incorporation
      of four phenoxazine bases into a previously optimized C-5 propyne pyrimidine
      modified 7-mer phosphorothioate oligonucleotide targeting SV40 large T antigen
      enhanced in vitro binding affinity for its RNA target and redirected RNAse H
      mediated cleavage as compared with the 7-mer C-5 propynyl phosphorothioate
      oligonucleotide (S-ON). The phenoxazine/C-5 propynyl U 7-mer S-ON showed dose
      dependent, sequence-specific, and target-selective antisense activity following
      microinjection into cells. Incubation of the phenoxazine/C-5 propynyl U S-ON with
      a variety of tissue culture cells, in the absence of any cationic lipid, revealed
      unaided cellular penetration, nuclear accumulation, and subsequent antisense
      activity. The unique permeation properties and gene-specific antisense activity
      of the 7-mer phenoxazine/C-5 propynyl U S-ON paves the way for developing potent,
      cost-effective, self-permeable antisense therapeutics.

PMID- 9920269
TI  - High-throughput quantitative histological analysis of Alzheimer's disease
      pathology using a confocal digital microscanner.
AB  - To develop a rapid method of quantifying immunohistochemical information in
      tissue sections, we tested a confocal laser fluorescence microscanner initially
      designed for DNA microarray analysis. This instrument collects digital images at
      multiple wavelengths, scans entire sections at a resolution of 5 or 10 microm in
      less than 10 min, and quantifies structures labeled with fluorescent or
      nonfluorescent probes. We assessed the microscanner by studying immunostained
      amyloid plaques in the Alzheimer's disease (AD) brain and in the brain of a
      transgenic mouse model of AD amyloidosis, as efforts to correlate measures of
      amyloid plaques in brain sections with behavioral impairments are impeded by
      limitations in current morphometric methods. Microscanner analysis was used to
      determine amyloid burden in the occipital and entorhinal cortices of the mouse
      (3.7%) and human AD brain (1.6%). We also quantified the colocalization of plaque
      beta-amyloid (Abeta) with glial fibrillary acidic protein, a marker of gliosis
      (mouse 0.9%, human AD 3.7%). The microscanner may be generally applicable to a
      wide variety of human histopathologies and their animal models, wherever rapid
      unbiased quantitative analysis is needed.

PMID- 9920270
TI  - Evolutionary molecular engineering by random elongation mutagenesis.
AB  - We describe a new method of random mutagenesis that employs the addition of
      peptide tails with random sequences to the C-terminal of enzyme molecules. A
      mutant population of catalase I from Bacillus stearothermophilus prepared by this
      method has a diversity in thermostability and enzyme activity equal to that
      obtained after random point mutagenesis. When a triple mutant of catalase I
      (I108T/D130N/1222T)-the thermostability of which is much lower than that of the
      wild type-was subjected to random elongation mutagenesis, we generated a mutant
      population containing only mutants with higher thermostability than the triple
      mutant. Some had an even higher stability than the wild-type enzyme, whose
      thermostability is considered to be optimized. These results indicate that
      peptide addition expands the protein sequence space resulting in a new fitness
      landscape. The enzyme can then move along the routes of the new landscape until
      it reaches a new optimum. The combination of random elongation mutagenesis with
      random point mutagenesis should be a useful approach to the in vitro evolution of
      proteins with new properties.

PMID- 9920271
TI  - In vitro selection of an allosteric ribozyme that transduces analytes to
      amplicons.
AB  - We have selected an allosteric ribozyme ligase from a random sequence population
      that is activated up to 10,000-fold by oligonucleotide effectors. The ribozyme
      conforms to a classic two-state model for allostery in which the equilibrium
      between inactive and active conformers is dramatically altered by the presence of
      effector ligands. In the presence of the effector the allosteric ribozyme ligase
      generates templates that can subsequently be amplified using conventional
      amplification technologies, such as RT-PCR. Thus, the allosteric ribozyme can
      transduce (or convert) analytes into amplicons. We demonstrate two potential
      diagnostic applications of the selected allosteric ribozyme ligase: 'counting'
      short oligonucleotide effectors by RT-PCR, and counting a non-nucleic acid
      effector, ATP, by ligation.

PMID- 9920272
TI  - Engineering a regulatable enzyme for homogeneous immunoassays.
AB  - We have engineered the phage displayed TEM-1 beta-lactamase to generate enzymes
      that can be used in homogeneous immunoassays because their activity can be
      modulated by binding to monoclonal antibodies (Mabs) raised against an unrelated
      protein. Random peptide libraries were genetically inserted into three loops to
      create hybrid enzymes with binding sites for Mabs. Insertion points were chosen
      to be close enough to the active site that complex formation could affect the
      activity. The antibiotic resistance provided by the beta-lactamase activity was
      used to select the clones encoding active enzymes. Biopanning of the active
      libraries on immobilized Mabs against the prostate specific antigen (PSA) or on
      streptavidin yielded enzymes with binding sites for these proteins. Their
      activity could be regulated by Mab or streptavidin binding. The dissociation
      constants of the complexes are in the 10(-9) to 10(-6) M range. In a competitive
      assay, PSA could be detected at a minimal concentration of 10(-9) M. The Mabs
      recognize mimotopes as no sequence similarity was found between inserts in
      regulated clones and fragments of the PSA sequence. The method can be developed
      to generate signaling molecules to be used for the detection of analytes in
      solution without identification of the epitope.

PMID- 9920274
TI  - High-level expression of maize phosphoenolpyruvate carboxylase in transgenic rice
      plants.
AB  - Using an Agrobacterium-mediated transformation system, we have introduced the
      intact gene of maize phosphoenolpyruvate carboxylase (PEPC), which catalyzes the
      initial fixation of atmospheric CO2 in C4 plants into the C3 crop rice. Most
      transgenic rice plants showed high-level expression of the maize gene; the
      activities of PEPC in leaves of some transgenic plants were two- to threefold
      higher than those in maize, and the enzyme accounted for up to 12% of the total
      leaf soluble protein. RNA gel blot and Southern blot analyses showed that the
      level of expression of the maize PEPC in transgenic rice plants correlated with
      the amount of transcript and the copy number of the inserted maize gene.
      Physiologically, the transgenic plants exhibited reduced O2 inhibition of
      photosynthesis and photosynthetic rates comparable to those of untransformed
      plants. The results demonstrate a successful strategy for installing the key
      biochemical component of the C4 pathway of photosynthesis in C3 plants.

PMID- 9920273
TI  - Enzyme modification by polymers with solubilities that change in response to
      photoirradiation in organic media.
AB  - We have synthesized a hybrid subtilisin the solubility of which can be regulated
      by photoirradiation through coupling with a photoresponsive copolymer that
      carries spiropyran groups in its side chains. The copolymer was synthesized by
      polymerization of methacrylate, methacrylic acid, and spiropyran-carrying
      methacrylate. It was then covalently bonded to the amino groups of subtilisin
      Carlsberg via its carboxyl groups using a carbodiimide coupling agent. The hybrid
      subtilisin was perfectly soluble in toluene and efficiently catalyzed
      transesterification. After ultraviolet irradiation, the hybrid subtilisin
      precipitated and was easily and quantitatively recovered by centrifugation.
      Recovered hybrid subtilisin, resolubilized by visible light irradiation, retained
      its original transesterification activity even after several cycles of
      precipitation and solubilization.

PMID- 9920275
TI  - Biotechnology patent applications in Europe. A look at the differences between
      French, British, and German patent application trends.

PMID- 9920276
TI  - Dynamic allele-specific hybridization. A new method for scoring single nucleotide
      polymorphisms.

PMID- 9920277
TI  - Biosafety and regulation.

PMID- 9920278
TI  - Cancer multidrug resistance.

PMID- 9920279
TI  - Nuclear factor-kappaB/Rel proteins: a point of convergence of signalling pathways
      relevant in neuronal function and dysfunction.
AB  - Nuclear factor-kappaB (NF-kappaB)/Rel designates a family of transcription
      factors participating in the activation of a wide range of genes crucially
      involved in immune and inflammatory function. NF-kappaB/Rel proteins have been
      demonstrated recently in primary neurons and in several brain areas. Functional
      significance of these proteins is still not understood completely, but since
      certain subsets of neurons appear to contain constitutively active DNA-binding
      activity, it seems likely that they may participate in normal brain function. A
      growing body of evidence is accumulating for a specific activation of NF
      kappaB/Rel proteins in the CNS, and in particular in neuronal cells, during
      neurodegenerative processes associated to etiologically unrelated conditions.
      Whether NF-kappaB activation is part of the neurodegenerative process or of
      protective mechanisms is a matter of debate. This issue will be reviewed here
      with particular attention to the available reports on the activity of NF
      kappaB/Rel proteins in both experimental paradigms of neurodegeneration and post
      mortem brain tissue of patients affected by various neurological diseases. We
      hypothesize that NF-kappaB/Rel proteins may represent the point of convergence of
      several signalling pathways relevant for initiating or accelerating the process
      of neuronal dysfunction and degeneration in many neurological diseases, including
      Parkinson's disease, Alzheimer's disease, CNS viral infections, and possibly
      others. If NF-kappaB/Rel proteins represent an integrating point of several
      pathways potentially contributing to neuronal degeneration, molecules that finely
      modulate their activity could represent a novel pharmacological approach to
      several neurological diseases.

PMID- 9920280
TI  - Innovative treatment programs against cancer: II. Nuclear factor-kappaB (NF
      kappaB) as a molecular target.
AB  - Nuclear factor-kappaB (NF-kappaB) activity affects cell survival and determines
      the sensitivity of cancer cells to cytotoxic agents as well as to ionizing
      radiation. Preventing the protective function of NF-kappaB may result in chemo-
      and radio-sensitization of cancer cells. Therefore, NF-kappaB has emerged as one
      of the most promising molecular targets in rational drug design efforts of
      translational cancer research programs.

PMID- 9920281
TI  - Prevention of oxidant-induced cell death in Caco-2 colon carcinoma cells after
      inhibition of poly(ADP-ribose) polymerase and Ca2+ chelation: involvement of a
      common mechanism.
AB  - The human colon carcinoma cell line Caco-2 was exposed to the oxidative stress
      inducing agents menadione (MEN), 2,3-dimethoxy-1,4-naphthoquinone, and hydrogen
      peroxide. All three agents caused DNA damage which was assessed by alkaline
      unwinding. Further, all three agents induced intensive NAD+ depletion, followed
      by a decrease in intracellular ATP and viability. Inhibition of poly(ADP-ribose)
      polymerase (PARP, EC 2.4.2.30) by 3-aminobenzamide prevented the depletion of
      NAD+. These cells had a higher viability and ATP content. The most pronounced
      effect was observed with 25 microM of MEN, while at higher levels a partial
      preservation of NAD+ was observed with no effect on ATP or viability. The
      chelation of intracellular calcium by bis-(o-aminophenoxy)-ethane-N,N,N1,N1
      tetraacidic acid/tetraacetoxymethyl) ester also prevented the dramatic loss of
      NAD+, demonstrating that Ca2+ is an activating factor in PARP-mediated cell
      killing.

PMID- 9920282
TI  - Quinone toxicity in DT-diaphorase-efficient and -deficient colon carcinoma cell
      lines.
AB  - The human colon carcinoma cell lines Caco-2 and HT-29 were exposed to three
      structurally related naphthoquinones. Menadione (MEN), 1,4-naphthoquinone (NQ),
      and 2,3-dimethoxy-1,4-naphthoquinone (DIM) redoxcycle at similar rates, NQ is a
      stronger arylator than MEN, and DIM does not arylate thiols. The Caco-2 cell line
      was particularly vulnerable to NQ and MEN and displayed moderate toxic effects of
      DIM. The HT-29 cell line was only vulnerable to NQ and MEN after inhibition of DT
      diaphorase (DTD) with dicoumarol, whereas dicoumarol did not affect the toxicity
      of quinones to Caco-2 cells. DTD activity in the HT-29 and Caco-2 cell lines, as
      estimated by the dicoumarol-sensitive reduction of 2,6-dichlorophenolindophenol,
      was 393.7 +/- 46.9 and 6.4 +/- 2.2 nmol NADPH x min(-1) x mg protein(-1),
      respectively. MEN depleted glutathione to a small extent in the HT-29 cell line,
      but a rapid depletion similar to Caco-2 cells was achieved when dicoumarol was
      added. The data demonstrated that the DTD-deficient Caco-2 cell line was more
      vulnerable to arylating or redoxcycling quinones than DTD-expressing cell lines.
      Exposure of the Caco-2 cell line to quinones produced a rapid rise in protein
      disulphides and oxidised glutathione. In contrast to NQ and DIM, no intracellular
      GSSG was observed with MEN. The relatively higher levels of ATP in MEN-exposed
      cells may account for the efficient extrusion of intracellular GSSG. The
      reductive potential of the cell as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide reduction was only increased by MEN and not with NQ
      and DIM. We conclude that arylation is a major contributing factor in the
      toxicity of quinones. For this reason, NQ was the most toxic quinone, followed by
      MEN, and the pure redoxcycler DIM elicited modest toxicity in Caco-2 cells.

PMID- 9920283
TI  - Inhibition of calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activity by dimethyl
      sulfoxide.
AB  - Membrane-bound (Ca2+ + Mg2+)-ATPase activity from human erythrocyte white ghosts
      in the calmodulin-activated state was inhibited by DMSO in concentrations of 3%
      (v/v) and above. At 10%, DMSO inhibited calmodulin activation by 47.7%, while
      basal, calmodulin-independent (Ca2+ + Mg2+)-ATPase and (Mg2+)-ATPase activity
      remained unaffected. (Na+ + K+)-ATPase activity was also reduced but exhibited a
      greater IC50. Concentration-effect analyses showed the inhibition by 10% DMSO to
      be a reversible, non-competitive effect with regard to calmodulin, Ca2+, and
      substrate activation. Calmodulin-stimulated processes may be more susceptible to
      inhibition by DMSO than related enzymatic catalysis, and thus may help explain
      the multitude of reported cellular events caused by the solvent. Furthermore,
      DMSO affected membrane-associated enzymatic mechanisms opposite to those reported
      for purified enzyme outside its native membrane environment.

PMID- 9920284
TI  - Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a
      receptor-mediated endocytosis mechanism.
AB  - Bleomycin (BLM) does not diffuse through the plasma membrane but nevertheless
      displays cytotoxic activity due to DNA break generation. The aim of the study was
      to describe the mechanism of BLM internalisation. We previously provided evidence
      for the existence of BLM-binding sites at the surface of DC-3F Chinese hamster
      fibroblasts, as well as of their involvement in BLM cytotoxicity on DC-3F cells
      and related BLM-resistant sublines. Here we report that A253 human cells and
      their BLM-resistant subline C-10E also possessed a membrane protein of ca. 250
      kDa specifically binding BLM. Part of this C-10E cell resistance could be
      explained by a decrease in the number of BLM-binding sites exposed at the cell
      surface with respect to A253 cells. The comparison between A253 and DC-3F cells
      exposing a similar number of BLM-binding sites revealed that the faster the fluid
      phase endocytosis, the greater the cell sensitivity to BLM. Moreover, the
      experimental modification of endocytotic vesicle size showed that BLM
      cytotoxicity was directly correlated with the flux of plasma membrane area
      engulfed during endocytosis rather than with the fluid phase volume incorporated.
      Thus, BLM would be internalised by a receptor-mediated endocytosis mechanism
      which would first require BLM binding to its membrane receptor and then the
      transfer of the complex into intracellular endocytotic vesicles, followed by BLM
      entry into the cytosol, probably from a nonacidic compartment.

PMID- 9920285
TI  - Tyrosine kinase activity of purified recombinant cytoplasmic domain of platelet
      derived growth factor beta-receptor (beta-PDGFR) and discovery of a novel
      inhibitor of receptor tyrosine kinases.
AB  - Aberrant expression of platelet-derived growth factor and its receptor (PDGFR)
      has been implicated in various human disorders, including cardiovascular disease
      and certain types of cancer. Inhibitors of the tyrosine kinase activity of PDGFR
      are leads in the development of novel agents to combat these diseases. We
      describe here a novel, potent inhibitor of PDGFR tyrosine kinase, 3-(4
      dimethylamino-benzylidenyl)-2-indolinone (DMBI). The compound also inhibits
      signal transduction through fibroblast growth factor receptor 1 (FGFR1), but is
      not active towards epidermal growth factor receptor (EGFR) or c-Src tyrosine
      kinase. The activity of DMBI and other tyrosine kinase inhibitors was compared in
      a cell-based assay as well as in an assay based on purified recombinant platelet
      derived growth factor beta-receptor (beta-PDGFR) lacking the transmembrane and
      ligand-binding domain. We showed that this truncated beta-PDGFR could dimerize,
      and that dimerization was required for tyrosine kinase activity. Tyrosine kinase
      activity was modulated by inhibitors of beta-PDGFR autophosphorylation in cells,
      but not by specific inhibitors of EGFR or c-Src tyrosine kinase. We conclude that
      beta-PDGFR lacking the transmembrane and ligand-binding domain retains the
      essential properties of the full-length receptor tyrosine kinase.

PMID- 9920286
TI  - Differences in the order of potency for agonists but not antagonists at human and
      rat adenosine A2A receptors.
AB  - To examine possible species differences in pharmacology, rat adenosine A2A
      receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in
      Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor
      cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4
      triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax
      (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively.
      The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in
      the two cell types, respectively. The order of potency of antagonists and most
      agonists was the same in both cell types, but 2-phenylaminoadenosine and 2
      chloroadenosine were relatively less potent in PC12 cells than in CHO cells. In
      the functional assay, using cyclic AMP accumulation, all agonists tested were
      more potent in CHO than in PC12 cells, but this could not be readily explained by
      differences in adenylyl cyclase or in the expression of G proteins. As in the
      case of binding, the relative agonist potencies were similar for most compounds,
      but 2-phenylaminoadenosine and 2-chloroadenosine were more potent at human A2A
      receptors in CHO cells than predicted from the data obtained on rat A2A receptors
      in PC12 cells. Antagonists were approximately equipotent in the two cells. These
      results show that, despite only small differences in amino acid sequences and no
      difference in antagonist pharmacology, the relative order of potency of receptor
      agonists can differ between species homologues of the adenosine A2A receptor.

PMID- 9920287
TI  - Methylenedioxy group and cyclooctadiene ring as structural determinants of
      schisandrin in protecting against myocardial ischemia-reperfusion injury in rats.
AB  - As a preliminary investigation to exploring whether the methylenedioxy group and
      the cyclooctadiene ring of the dibenzo[a,c]cyclooctadiene (schisandrin) molecule
      plays an important role in the protection against myocardial ischemia-reperfusion
      (IR) injury, we examined the effects of three schisandrins, namely schisandrin A
      (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), and the effect of
      dimethyl-4,-4'-dimethoxy-5,6,5',6'-dimethylene-dioxy-biphenyl-2,2' -bicarboxylate
      (DDB), an intermediate compound derived from the synthesis of Sch C, on
      myocardial IR injury in isolated Langendorff-perfused rat hearts. While
      pretreating rats with Sch A or DDB at a daily oral dose of 1.2 mmol/kg for 3 days
      did not protect the isolated-perfused hearts against IR-induced damage,
      pretreatment with Sch B or Sch C at the same dosage regimen produced
      cardioprotective action. The extent of cardioprotection afforded by Sch B or Sch
      C pretreatment correlated well with the degree of enhancement in myocardial
      glutathione antioxidant status, as indicated by significant increases in the
      tissue-reduced glutathione level and Se-glutathione peroxidase (EC 1.11.1.9),
      glutathione transferases (EC 2.5.1.18), and glutathione reductase (EC 1.6.4.2)
      activities in ischemic-reperfused hearts when compared with the unpretreated IR
      control. Our results indicate that both the methylenedioxy group and the
      cyclooctadiene ring of the schisandrin molecule are important structural
      determinants in mediating the protection against myocardial IR injury.

PMID- 9920288
TI  - Metabolism of antitumor acylfulvene by rat liver cytosol.
AB  - Illudins are novel compounds from which a potent class of antitumor agents,
      called acylfulvenes, have been synthesized. The model illudin, illudin S, has
      marked in vitro and in vivo toxicity but displays a poor therapeutic index. The
      toxicity of illudin S is believed to involve a combination of enzymatic reduction
      and chemical reaction. Enzymatic reduction by a cytosolic NADPH-dependent enzyme
      produces an aromatic metabolite, as does reaction with thiols. Acylfulvene is
      formed from illudin S by reverse Prins reaction. Acylfulvene is 100-fold less
      toxic in vitro and in vivo than illudin S but possesses marked antitumor efficacy
      in vivo, thus displaying opposite properties from illudin S. For this reason we
      investigated the in vitro metabolism of acylfulvene. Incubation of acylfulvene
      with NADPH and rat liver cytosol yielded two metabolites. One metabolite, the
      aromatic product, is similar to that obtained with illudin S in this in vitro
      system and was anticipated. The other metabolite, the hydroxylated product, was
      not expected and no corresponding metabolite for illudin S could be detected. The
      production of this hydroxylated metabolite from acylfulvene may explain, in part,
      the increased antitumor activity of novel acylfulvenes as compared with the
      illudins.

PMID- 9920289
TI  - Metabolic effects of a methylthioadenosine phosphorylase substrate analog on
      African trypanosomes.
AB  - The effects of 5'-deoxy-5'-(hydroxyethylthio)adenosine (HETA), a trypanocidal
      analog of 5'-deoxy-5'-(methylthio)adenosine (MTA), on polyamine synthesis and S
      adenosylmethionine (AdoMet) metabolism were examined in bloodstream forms of
      Trypanosoma brucei brucei. HETA was cleaved by trypanosome MTA phosphorylase at
      the same rate as the natural substrate, MTA, in a phosphate-dependent reaction.
      Fluorine substitution at the 2-position of the purine ring increased activity by
      approximately 50%, whereas substitution with an amino group reduced activity to
      about one-third of the control. HETA was accumulated by trypanosomes with
      internal concentrations of 100-250 microM and >800 microM after a 15-min
      incubation with 1 and 10 microM, respectively. Trypanosomes preincubated with
      HETA metabolized it at a rate of 21.9 nmol/hr/mg protein. Preincubation of cells
      with HETA at 1 or 10 microM inhibited spermidine synthesis from [3H]ornithine by
      22-37%, and increased the cytosolic levels of AdoMet by 2- to 5-fold and that of
      MTA by up to 8-fold. S-Adenosylhomocysteine (AdoHcy) levels also increased 1.5-
      to 7-fold in treated cells, whereas decarboxylated AdoMet decreased 65%.
      Preincubation of trypanosomes with HETA for 4 hr also reduced the incorporation
      of [35S]methionine in trichloroacetic acid-precipitable material by 50-60%, and
      reduced the methyl group incorporation into protein from [U-14C]methionine by 65
      70%. Thus, HETA interferes with a series of biochemical events involving the
      participation of AdoMet and methionine in polyamine synthesis, protein synthesis,
      and transmethylation reactions.

PMID- 9920290
TI  - Induction of human breast cancer cell apoptosis from G2/M preceded by stimulation
      into the cell cycle by Z-1,1-dichloro-2,3-diphenylcyclopropane.
AB  - We have shown previously that Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a.
      Analog II, A(II)) inhibits human breast cancer cell proliferation regardless of
      estrogen receptor status or estrogen sensitivity, and that its cellular targets
      include microtubules. In the present study, we investigated the apoptosis
      inducing effects of A(II). MCF-7, MCF-7/LY2, and MDA-MB-231 cells all showed
      nuclear fragmentation in response to 100 microM A(II) when stained with Hoechst
      33342 and examined by fluorescence microscopy. Pulsed field gel electrophoretic
      analysis showed that each of the cell lines also developed specific high
      molecular weight DNA fragments: a low level of 1-2 Mb fragments appeared after 6
      hr, while 30-50 kb fragments accumulated subsequently. At 24 hr of drug exposure,
      the majority of cells became nonadherent, and the 30-50 kb fragments were
      restricted to detached MCF-7 and MDA-MB-231 cells. Both adherent and detached MCF
      7/LY2 cells exhibited these fragments. A previous study by single-color
      (propidium) flow cytometry demonstrated that A(II) blocks MDA-MB-231 cells in
      G2/M of the cell cycle. More refined analyses in the present study showed this
      same result for MDA-MB-231 cells, but MCF-7 and MCF-7/LY2 cells did not reveal
      apparent drug-induced cell cycle block. A(II) demonstrated growth inhibitory,
      cell cycle-perturbing, and hypodiploidy-inducing activity against other human
      breast carcinoma lines, i.e. BT-20, CAMA-1, and SKBR-3, but no such actions in
      the non-tumorigenic, "normal" human breast epithelial line MCF-10A.
      Bromodeoxyuridine labeling and two-color flow cytometric analysis, however,
      suggested that A(II) caused stimulation into S phase, and that G2/M was the phase
      of the cell cycle from which cells apoptosed. A(II) caused cell rounding,
      detachment from the growth matrix, and nuclear shrinkage and fragmentation in
      parallel with biochemical changes. Cycloheximide inhibited A(II)-induced cell
      death, indicating that its toxicity requires de novo protein synthesis.

PMID- 9920291
TI  - Inhibition by tetanus toxin of sodium-dependent, high-affinity [3H]5
      hydroxytryptamine uptake in rat synaptosomes.
AB  - Tetanus toxin (TeTx) is a powerful clostridial neurotoxin that inhibits Ca2+
      dependent neurotransmitter secretion as do the botulinum neurotoxins (BoNTs). We
      found that TeTx (but not BoNT/A) produced a specific time- and dose-dependent
      inhibition of Na+-dependent [3H]5-hydroxytryptamine (serotonin, 5-HT) uptake in
      rat CNS synaptosomes. This effect was found in all CNS tryptaminergic areas,
      being maximal in the hippocampus and occipital cortex. TeTx produced the maximum
      reduction in [3H]5-HT uptake after 30 min of preincubation, being significant
      also at lower doses (10(-12) M) or shorter incubation times (10 min). Serotonin
      transport inhibitors such as fenfluramine (IC50, 11.0 +/- 0.9 microM), paroxetine
      (IC50, 33.5 +/- 0.1 microM), and imipramine (IC50, 89.9 +/- 5.7 microM) were 3 or
      4 orders of magnitude less potent than TeTx (IC50, 8.7 +/- 1.0 nM). Of the two
      fragments of TeTx, (the C-terminal portion of the neurotoxin heavy chain, which
      is responsible for the binding to the nerve tissue) was consistently more
      effective than the L-H(N) fragment (the light neurotoxin chain disulfide linked
      to the N-terminal portion of the heavy chain, which is responsible for the toxic
      metalloprotease action) as inhibitor of [3H]5-HT uptake in synaptosomal
      preparations (56 +/- 5% and 95 +/- 3% with respect to control, respectively).
      Antagonism of the toxin-induced [3H]5-HT uptake blockade could not be reversed by
      zinc chelators but did have the ability to antagonize the TeTx inhibition of
      basal and K+-evoked [3H]5-HT release in rat synaptosomes. The reduction in
      serotonin accumulation induced by TeTx could be responsible for some tetanic
      symptoms that have been related to the serotonergic system.

PMID- 9920292
TI  - Presidential address. What does the Millennium have in store for the American
      Society of Parasitologists?

PMID- 9920293
TI  - Acceptance of the 1998 Henry Baldwin Ward Medal.

PMID- 9920294
TI  - Presentation of the 1998 recipient of the American Society of Parasitologists'
      Mentor Award, Dr. Austin J. MacInnis.

PMID- 9920295
TI  - Acceptance of the American Society of Parasitologists' Mentor Award. Mentoring:
      the honor, the privilege, the responsibility.

PMID- 9920296
TI  - Evidence that the factor used by the tapeworm, Hymenolepis diminuta, to direct
      the foraging of its intermediate host, Tribolium confusum, is a volatile
      attractant.
AB  - We have previously demonstrated that flour beetles, Tribolium confusum, are more
      attracted to the feces from rats with patent Hymenolepis diminuta infections than
      to feces from uninfected rats. The objective of this study was to determine if
      this effect is due to a volatile attractant. Volatile substances emitted by feces
      from H. diminuta-infected rats or from uninfected controls were collected by
      aspirating fresh rat feces, while trapping the volatiles on Porapak Q (a solid
      adsorbant). The volatiles were eluted from the Porapak Q with diethyl ether, and
      the relative attractancy of the volatiles to prestarved beetles was assessed by
      bioassay. More beetles were attracted to volatiles of feces from infected rats
      than to volatiles of feces from uninfected controls (P< or =0.0001). The
      magnitude of the response varied with the time in the bioassay test arena and
      also the concentration of the volatiles (P< or =0.0232). When the volatiles we re
      concentrated by aspirating more boli over a longer period of time, the beetles
      responded more quickly and in greater numbers to the volatiles of feces from
      infected rats. The experiments presented here provide the first indication that a
      tapeworm (H. diminuta) can enhance its chances of transmission by directing the
      foraging of its intermediate host (T. confusum) through the use of attractive,
      volatile material released from the feces of its definitive host.

PMID- 9920297
TI  - Parasite-altered behavior in a crustacean intermediate host: field and laboratory
      studies.
AB  - The effects of the acanthocephalan parasite Pomphorhynchus laevis on the behavior
      of its crustacean intermediate host, the amphipod Echinogammarus stammeri, were
      studied. A drift study revealed that infected amphipods were disproportionately
      represented in drift samples taken throughout a 24-hr period; infection with more
      than 1 parasite enhanced this effect. Infection also interacted with the daily
      timing of drift, with parasitized amphipods beginning to drift earlier in the
      evening. Two distinct behaviors quantified in laboratory settings may play a role
      in this increased drifting behavior: parasitized amphipods showed (1) an
      increased preference for an illuminated environment and (2) increased activity in
      comparison to nonparasitized conspecifics. These results are consistent with
      previous studies on the effects of P. laevis on another amphipod host, Gammarus
      pulex, and provide new data on the activity level of P. laevis-infected
      amphipods.

PMID- 9920298
TI  - Arachidonic acid metabolism to prostaglandin E2, D2, F2alpha, and I2 in the
      plerocercoid of Spirometra erinaceieuropaei.
AB  - Changes in the fatty acid composition of phospholipid and triglyceride fractions
      in Spirometra erinaceieuropaei plerocercoids were investigated after 0, 0.5, 1,
      3, and 6 hr incubation at 10 C and 37 C with physiological saline containing 5 mM
      arachidonic acid and 10 mg/ml bovine serum albumin, pH 7.0. At 37 C, arachidonic
      acid was absorbed and incorporated rapidly into the triglyceride fraction (over
      14.4% in composition), and decreased after 2-3 hr; at 10 C, the amount of
      triglyceride increased slowly and continued to a maximum of 12.9% during 6 hr of
      incubation. We used a simplified method to extract and purify prostaglandins from
      the plerocercoid of S. erinaceieuropaei. Prostaglandins were quantified using gas
      chromatography-mass spectrometry. Prostaglandin E2, PGD2, PGF2alpha, and 6-keto
      PGF1alpha were detected under different incubation conditions. In the dose
      dependent experiment, PGD2 was detected in plerocercoids incubated with 0.5, 1,
      2, and 5 mM arachidonic acid, pH 7.0, at 25 C; PGE2 was detected with 2 and 5 mM
      arachidonic acid. In the time-dependent experiment, where plerocercoids were
      incubated with 5 mM arachidonic acid, pH 7.0 at 25 C, PGF2alpha was first
      detected at 15 min; thereafter, 6-keto-PGF1alpha was detected at 30 min and PGD2
      and PGE2 were detected at 1 hr. Thromboxane B2 was not detected in either the
      dose-dependent or time-dependent experiments, and only PGE2 was detected in the
      incubation medium with 5 mM arachidonic acid at 1 hr. These results reveal that
      when plerocercoids change from reptilian to mammalian hosts, they are able to
      absorb and modify arachidonic acid bound to albumin and generate prostaglandins
      under suitable conditions. Prostaglandins exhibit potent biological functions for
      immunoresponses that may be relevant to parasitism and the success of larva
      migrans in S. erinaceieuropaei.

PMID- 9920299
TI  - Physiological responses of deer mice (Peromyscus maniculatus) to infection with
      Capillaria hepatica (Nematoda).
AB  - Negative effects due to infection have not been documented for most natural host
      parasite associations. I performed an infection experiment to measure the
      physiological consequences of infection by Capillaria hepatica in deer mice
      (Peromyscus maniculatus gracilis). Compared to their uninfected siblings,
      infected mice displayed increased serum concentrations of alkaline phosphatase
      and total proteins and reduced concentrations of albumin. Infected mice also had
      higher hematocrits and enlarged livers and spleens. There was no difference in
      swimming endurance between infected and control animals, possibly because mice
      did not perform at maximum aerobic capacity. Sex differences in alkaline
      phosphatase and albumin levels suggest that females are more sensitive to similar
      burdens of C. hepatica. Different hematocrit responses between mice from 2
      localities suggest that historical associations can lead to evolutionary change
      in pathophysiology caused by this nematode. Further experiments would reveal
      whether these disturbances lead to reductions in host fitness.

PMID- 9920300
TI  - Seasonal patterns in the biology of Eubothrium salvelini infecting brook trout in
      a creek in lower Michigan.
AB  - A total of 392 brook trout, Salvelinus fontinalis, and 211 slimy sculpin, Cottus
      cognatus, was examined for Eubothrium salvelini (Cestoda) from May 1995 through
      September 1996 from Sweetwater Creek, Michigan. No seasonal pattern in
      prevalence, intensity, and abundance of parasites in trout and sculpin was
      determined. However a seasonal pattern in the length and percent gravid E.
      salvelini in brook trout suggests that recruitment of this parasite occurs during
      late summer and early fall. During this time the procercoid in the copepod
      intermediate host is expected to be available in the environment for fish to
      recruit, but a total of 6,399 copepods was not infected. Gravid worms were not
      found in slimy sculpin, suggesting it is a paratenic or dead-end host. Detailed
      studies on the biology of parasites may be more indicative of seasonal
      transmission patterns than studies that only measure prevalence, abundance, and
      intensity.

PMID- 9920301
TI  - Entomopathogenic nematodes as control agents of developmental stages of the black
      legged tick, Ixodes scapularis.
AB  - Thirteen species or strains of entomopathogenic nematodes of the genera
      Steinernema and Heterorhabditis were tested in vitro against unfed and engorged
      larvae, nymphs, and adults of the black-legged tick, Ixodes scapularis. Nematodes
      were pathogenic to engorged female ticks, but not to unfed or engorged larvae,
      nymphs, males, and unfed females. Steinernema riobravis (355) and Heterorhabditis
      megidis (M145) killed ticks most rapidly, with mean day of death postinfection of
      2.5 and 3.5 days, respectively. However, all nematode strains and species were
      lethal to engorged female ticks within 7.5 days. Development of juveniles and
      reproduction of nematodes did not occur inside the tick cadavers, because no
      infective juveniles (IJs) emerged from cadavers after 40 days, and no nematode
      life-cycle stages other than the primary IJs could be isolated from cadavers. Egg
      masses were produced by 4 of 702 nematode-infected, engorged females. Egg masses
      produced were not significantly smaller than masses produced by control ticks;
      however, only 1 of the 4 egg masses hatched, whereas all of the egg masses
      produced by the control ticks hatched. Entomopathogenic nematodes may be useful
      as an alternative management method for I. scapularis populations, and may be
      more acceptable than acaricidal chemicals for use in infested areas.

PMID- 9920302
TI  - Ultrastructure of spermiogenesis and the spermatozoon of Anoplocephaloides
      dentata (Cestoda, Cyclophyllidea, Anoplocephalidae), an intestinal parasite of
      Arvicolidae rodents.
AB  - Spermiogenesis in Anoplocephaloides dentata begins with the formation of a
      differentiation zone delimited by a ring of arched membranes. This conical area
      shows 2 parallel centrioles with associated anterior reduced striated roots but
      without an intercentriolar body. Only 1 of the centrioles develops an axoneme
      that grows into a cytoplasmic extension. Two crestlike bodies appear when the
      nucleus initiates its migration along the spermatid body. We describe for the
      first time at the end of spermiogenesis the formation of an apical cone before
      the strangulation of the ring of arched membranes. The mature spermatozoon of A.
      dentata is filiform, tapered at both ends, and lacks mitochondria. Its anterior
      extremity has an apical cone measuring about 1,400 x 350 nm and 2 crestlike
      bodies. Cortical microtubules are spiralled at an angle of about 30 degrees to
      the spermatozoon axis. The axoneme, of the 9+1 pattern of Trepaxonemata
      (Polycladida, Seriata, "Typhloplanoida," "Dalyellioida," and Neodermata lacks a
      periaxonemal sheath and does not reach the extremities of the spermatozoon.
      Numerous granules of electron-dense material are observed in the posterior
      regions of each spermatozoon. Analysis of ultrastructural features found during
      spermiogenesis in A. dentata corroborates the presence of striated roots
      associated with the centrioles in cyclophyllidean species. Moreover, the presence
      of striated roots is described for the first time in type IV spermiogenesis.

PMID- 9920303
TI  - Population genetic structure of a three-host tick, Amblyomma dissimile, in
      eastern Venezuela.
AB  - Patterns of genetic variation for the tick Amblyomma dissimile were analyzed from
      a total of 200 ticks collected on 12 toads (Bufo marinus), 14 snakes (Boa
      constrictor), and 8 lizards (Iguana iguana) at 11 localities. The analyses were
      performed on electrophoretic data from 8 isozyme loci. Mean heterozygosity per
      locus was 6% (+/-3.1) per population. Differences in allelic frequencies among
      ticks from different individual hosts were the major source of genetic
      variability in this study. Host species was a smaller source of genetic
      variation. Genetic distances between localities varied according to which host
      species was present in each locality, and these appeared to be related to the
      extent of habitat overlap between host species. The smallest genetic distances
      between samples from different host species were recorded for I. iguana and B.
      constrictor. In contrast, the genetic distances between tick samples from B.
      marinus and either of the reptile species were significantly larger than between
      tick samples from this amphibian species. Ecological variables or the geographic
      distance did not explain the local patterns of differentiation observed in A.
      dissimile. Major genetic differences between island and mainland sites (0.03702)
      suggested an association between genetic distances and geographic isolation. The
      consistency between patterns of genetic variation and those of host home range
      overlap suggests that host dispersion is the main force structuring the genetic
      variation within this tick species.

PMID- 9920304
TI  - Clonal population structure of Colombian sylvatic Trypanosoma cruzi.
AB  - Isoenzyme variability and evidence of genetic exchange were evaluated in 75 wild
      stocks of Trypanosoma cruzi obtained from different hosts from 5 geographical
      regions within the endemic area in Colombia. Cluster analysis of genetic
      variability was attempted. Thirty-three multilocus enzyme genotypes (clonets)
      were identified from 75 stocks, 27 of which clustered with zymodeme Z1 and 6 with
      zymodeme Z3. Two stocks isolated from human infections showed the potential risk
      to rural communities in Colombia. The stocks exhibited departures from Hardy
      Weinberg expectations, including both fixed heterozygote and fixed homozygote
      demes, where both segregation and recombination were absent. To inspect for
      population subdivision that might falsely imply clonality in these stocks,
      Wright's F statistics were calculated. Theta values (Fst) were significantly
      different from 0 when 33 clonets, 27 Z1-like clonets, and 5 geographical
      subpopulations were compared; thus, a significant amount of divergence has
      occurred between and within them. In addition, linkage disequilibrium was
      detected for most possible pairwise comparisons of loci. In conclusion, the above
      results all support a scenario of long-term clonal evolution in Colombian
      sylvatic T. cruzi populations.

PMID- 9920305
TI  - Hydrogen peroxide production in immune-reactive Drosophila melanogaster.
AB  - Upon infection with the wasp parasitoid Leptopilina boulardi, the blood cells or
      hemocytes of Drosophila melanogaster larvae become activated and manifest a type
      of communal phagocytosis wherein eggs of the parasitoid are enveloped by
      multicellular, melanotic capsules. Hemocytes engaged in this collaborative
      response generate reactive oxygen intermediates (ROI). These molecules, together
      with melanogenic intermediates, are believed to destroy intrahemocoelic
      parasites. Cellular uptake of 2',7'-dichlorofluorescin diacetate (DCF-DA) and the
      oxidation of its deacetylated form (DCF) to yield the fluorescent product
      dichlorofluorescein (DC) was used as an intracellular probe for oxidant
      generation. The selective uptake of the fluorescent probe only by activated
      plasmatocytes from immune-reactive larvae identified these hemocytes as the
      source of ROI. Inhibition of DCF oxidation by catalase established hydrogen
      peroxide (H2O2) as 1 of the principal oxidants generated during melanotic
      encapsulation. A sensitive spectrometric assay for assessing iron oxidation and
      complex formation with xylenol orange (FOX assay) also was used to document in
      vitro-enhanced H2O2-mediated oxidations by hemolymph from immune-competent
      larvae. Cumulative evidence now establishes both superoxide anion (O2-*) and its
      dismutation product H2O2 in the cellular encapsulation response of D.
      melanogaster.

PMID- 9920306
TI  - Isolation of a third species of Sarcocystis in immunodeficient mice fed feces
      from opossums (Didelphis virginiana) and its differentiation from Sarcocystis
      falcatula and Sarcocystis neurona.
AB  - Opossums (Didelphis virginiana) were found to be hosts for 3 species of
      Sarcocystis: Sarcocystis falcatula with an avian intermediate host, S. neurona
      with an undetermined intermediate host, and a third, unnamed, species. Sporocysts
      from the intestines of 2 opossums (nos. 26 and 47) were fed to budgerigars
      (Melopsittacus undulatus), nude mice, and gamma-interferon knockout (KO) mice.
      Sporocysts of S. falcatula were not infective to nude or KO mice. Sporocysts of
      S. neurona induced encephalitis in KO and nude mice; only schizonts and
      merozoites were found in tissues of mice, and they reacted with anti-S. neurona
      serum raised against the SN-2 isolate of S. neurona originally obtained from
      tissues of a paralyzed horse. All 3 species of Sarcocystis were present in
      opossum no. 47. Sarcocystis neurona was isolated in cell culture from this
      opossum. Sporocysts from opossum no. 47 were lethal to budgerigars, indicating S.
      falcatula infection. Only 1 species of Sarcocystis (the third species) was found
      in opossum no. 26; the sporocysts were infective to KO and nude mice. Schizonts
      and merozoites of this species were predominantly in the liver but were also
      found in other tissues; schizonts did not react with anti-S. neurona serum.
      Merozoites of the third species were ultrastructurally distinct from S. falcatula
      and S. neurona merozoites. Sarcocysts were found in leg muscles of 2 mice killed
      50 and 54 days after they were fed sporocysts from opossum no. 26. These
      sarcocysts had steeple-shaped protrusions on the cyst wall and were distinct from
      sarcocysts of S. falcatula and any other species of Sarcocystis.

PMID- 9920307
TI  - Infectivity of Cryptosporidium parvum oocysts stored in water at environmental
      temperatures.
AB  - Oocysts of Cryptosporidium parvum obtained from calves were cleaned of fecal
      debris by density gradient centrifugation and suspended in deionized water in
      microcentrifuge tubes. The tubes were placed in circulating water baths at
      temperatures of -10, -5, 0, 5, 10, 15, 20, 25, 30, or 35 C, and 2 tubes were
      removed from each water bath 1, 2, 4, 8, 12, 16, 20, and 24 wk later. Oocysts
      from 1 tube were administered at the rate of 1.5 x 10(5) oocysts per mouse to 2
      litters of neonatal BALB/c mice and were considered infective when developmental
      stages were found in histologic sections of mouse gut and/or a positive
      polymerase chain reaction (PCR) was obtained for C. parvum DNA in mouse ileum.
      The second tube was held at -70 C until tubes from all time periods were
      available, then oocysts within the tubes were assayed for amylopectin
      concentration. Oocysts held at -10 C were infectious up to 1 wk of storage, and
      those held at -5 C were infectious up to 8 wk of storage, as determined by PCR
      but not histology. Oocysts held at 0, 5, 10, 15, and 20 C were still infectious
      after 24 wk of storage. By microscopic examination of mouse tissue, oocysts held
      at 20 C infected only 1 of 10 mice after 24 wk of storage, and the number of
      developmental stages began declining after 4 wk of storage; those held at 25 and
      30 C each produced infections up to 12 wk after storage in 1 of 10 mice with
      reduced numbers of developmental stages beginning 4 wk after storage. Those held
      at 35 C produced light infections in 2 of 10 mice only up to 1 wk of storage.
      Amylopectin concentration decreased with increasing length of storage time or
      temperature. These findings provide a guide for estimating the potential duration
      of oocyst infectivity within a wide range of environmental temperatures and
      demonstrate the relationship between amylopectin concentration and infectivity.

PMID- 9920308
TI  - The effects of temperature and light on the survival, development, and
      infectivity of Plagiorchis elegans eggs.
AB  - Plagiorchis elegans eggs were incubated at 0, 4, 10, 20, or 30 C under a 12-hr:12
      hr (L:D) photoperiod for 120 days. Approximately one-quarter of the eggs had
      already initiated the process of embryonation when passed with the feces of the
      hamster (Mesocricetus auratus), the experimental definitive host. Eggs failed to
      embryonate at 0 C and died within 2 days. Incubation at 4 C allowed full
      embryonation, but the mean number of embryonated eggs per day (1.32+/-0.15) and
      the mean number of eggs available over the course of incubation (egg days)
      (219.00+/-2.24) remained low. These values increased progressively as incubation
      temperatures rose and reached levels of 3.59+/-0.30 and 1,467.50+/-4.56,
      respectively, at 20 C. Although incubation at 30 C further increased the mean
      number of eggs per day (5.45+/-0.56), the mean number of egg days declined
      sharply to 735.25+/-4.71, suggesting that elevated temperatures enhanced
      embryonation but lowered the survival of embryonated eggs. This was also
      reflected in the infectivity of eggs over time. Embryonated eggs incubated at 10
      and 20 C remained infective significantly longer than eggs incubated at higher or
      lower temperatures. Incubation in constant light yielded significantly lower mean
      numbers of embryonated eggs per day (1.86+/-0.09) and mean number of egg days
      (96.25+/-0.99) than incubation in constant darkness (2.23+/-0.17 and 701.50+/
      2.86 eggs, respectively) but did not affect the infectivity of embryonated eggs.
      The data suggest that at moderate temperatures and shielded from light, fully
      embryonated eggs of P. elegans may survive in the aquatic environment for a
      period of months. Such eggs may serve as a source of infection for populations of
      Stagnicola elodes and ensure the sustained production of the highly
      entomopathogenic cercariae required for mosquito control.

PMID- 9920309
TI  - Expression and localization of an S100 protein-like molecule in Eimeria tenella.
AB  - We investigated the expression of a calcium-binding protein, the S100 protein, in
      Eimeria tenella. Cecal paraffin sections from experimentally infected chickens
      were treated with anti-alpha-S100 (anti-alpha subunit of S100 protein) and anti
      beta-S100 (anti-beta subunit of S100 protein) monoclonal antibodies and anti-S100
      whole molecule polyclonal antibody. The avidin-biotin peroxidase method was used
      for immunocytochemical staining. Our results demonstrated a positive
      immunoreaction within the schizonts, macrogametes, and oocysts. These stages were
      all beta subunit and S100 whole-molecule positive. Immunoblot studies of the
      total proteins of E. tenella merozoites and sporozoites of the original strain
      and 2 precocious lines have demonstrated that precocious attenuation produced
      different S100 protein isotypes.

PMID- 9920310
TI  - Pathogenicity and lethality of a minute intestinal fluke, Neodiplostomum
      seoulense, to various strains of mice.
AB  - Pathogenicity and lethality of Neodiplostomum seoulense to various strains of
      mice (mast cell-deficient W/Wv, their normal littermate +/+, C57BL/6, BALB/cA,
      C3H/HeJ), and a hybrid (BALB/cA x C3H/HeJ)F1 were investigated. When the mice
      were infected orally each with 200 metacercariae, their abdomen became distended,
      and all mice died by day 23 postinfection (PI) except BALB/cA, which were
      severely weakened but recovered after 28 days. Even a smaller infection dose of
      25 metacercariae was highly lethal to C3H/HeJ mice. Despite treatment with
      praziquantel (3 mg/mouse) on day 10 PI, 80% of C57BL/ 6 mice did not recover and
      died. After day 14 PI, the whole intestine of C57BL/6 mice was contracted and
      significantly shortened in length, and charcoal meal transit was significantly
      faster compared with uninfected controls. After incubation in papaverine, the
      contracted intestines of C3H/HeJ mice did not relax, suggesting that the change
      is irreversible. In conclusion, N. seoulense has the potential to kill most
      strains of mice by causing irreversible damage to their intestine. The effects of
      mucosal mast cells on the survival rate of mice were negligible, because both
      W/Wv and +/+ mice died around day 20 PI.

PMID- 9920311
TI  - Meningoencephalitis due to a Sarcocystis neurona-like protozoan in Pacific harbor
      seals (Phoca vitulina richardsi).
AB  - Seven Pacific harbor seals with meningoencephalitis associated with Sarcocystis
      neurona-like protozoa are described. Six of the 7 seals were free-ranging and
      were found stranded over an 80-km stretch of central California coastline; the
      other was captive. All had marked to severe nonsuppurative meningoencephalitis,
      most severe in the cerebellar cortex. Immunohistochemistry for S. neurona
      antigens was positive on brain tissue in all cases, revealing numerous merozoites
      as well as developing and mature schizonts, including rosette forms. Electron
      microscopy performed on 3 animals revealed merozoites and schizonts consistent
      with Sarcocystis sp., with the absence of rhoptries in merozoites, lack of a
      parasitophorous vacuole around schizonts, and division by endopolygeny. Serology
      using western blotting revealed the presence of anti-S. neurona immunoglobulins
      in the sera of 4 of 5 seals tested. Four animals also had a concurrent mild to
      moderate nonsuppurative myocarditis; in 1 seal, rare sarcocysts of undetermined
      species were present within cardiomyocytes.

PMID- 9920312
TI  - One fate of epimastigote forms of Trypanosoma cruzi injected in mice. An
      ultrastructural study.
AB  - Recently, we suggested that epimastigote forms of Trypanosoma cruzi are cleared
      from circulation of mice by a mechanism independent of lysis and that platelets
      play an important role in this process. These observations prompted us to look at
      the fate of epimastigotes in the lung, liver, and spleen of mice injected
      intravenously with these parasite forms. Using transmission electron microscopy,
      we observed clumps of epimastigotes and platelets in direct contact with
      phagocytes in the lumen of capillaries. However, the platelets and parasites were
      probably separated before phagocytosis because only parasites were found inside
      the phagocytes. Indeed, most of the phagocytes, although containing epimastigotes
      in different stages of disintegration, contained no platelets. The removal of
      parasites from platelets was probably mediated by phagocytes through a mechanism
      similar to the removal of bacteria from the surface of erythrocytes in humans.
      These observations suggest that the nonvirulence of T. cruzi epimastigotes in
      mice is not due to lysis but probably to the inability of these parasite forms to
      escape destruction by the phagocytes.

PMID- 9920313
TI  - Lissorchis macropharynx n. sp. (Digenea: Lissorchiidae) from the shorthead
      redhorse, Moxostoma macrolepidotum (LeSueur) (Osteichthyes: Catostomidae).
AB  - Lissorchis macropharynx (Digenea: Lissorchiidae) is described from the shorthead
      redhorse, Moxostoma macrolepidotum (LeSueur) (Catostomidae) from the Assiniboine
      River drainage of southern Manitoba. The species is morphologically similar to
      Lissorchis hypentelii in possessing a similar body shape (widest at the ovarian
      region and a relatively long hindbody), a distinctly trilobed and relatively
      posteriorly situated ovary, and in the distribution of the vitellaria. It differs
      from L. hypentelii and all other lissorchiids in possessing a massive pharynx
      that is generally equal in length to or longer than the oral sucker and almost as
      deep as the cervical region of the body it occupies, a protruding acetabular
      region with an aspinose ridged/folded and grooved anterior surface, and a massive
      cirrus sac that reaches the level of the ovary. Museum specimens of Lissorchis
      spp. from M. macrolepidotum from other drainages in Manitoba and Wisconsin were
      also identified as L. macropharynx.

PMID- 9920314
TI  - Myxobolus petenensis n. sp (Myxosporea) from the circumorbital integument of
      Dorosoma petenense (Clupeidae) in Kentucky Lake.
AB  - Myxobolus petenensis n. sp. is described from the circumorbital integument of
      threadfin shad (Dorosoma petenense) in Kentucky Lake, Kentucky. Preserved spores
      are subspherical in frontal view and measure 10.1-13.1 microm long and 12.0-15.8
      microm wide. The polar capsules are pyriform and often unequal in size, with the
      larger capsule measuring 6.6-8.0 microm long and 4.8-5.7 microm wide and the
      smaller capsule 5.7-7.4 microm long and 4.2-5.5 microm wide. Examination of
      several clupeids, skipjack herring (Alosa chrysochloris), gizzard shad (D.
      cepedianum), and threadfin shad revealed M. petenensis to infect only threadfin
      shad. This report of M. petenensis is the first known species of Myxobolus
      infecting a species of freshwater fish of the family Clupeidae in North America.

PMID- 9920315
TI  - A new Eimeria species (Apicomplexa: Eimeriidae) infecting Onychomys species
      (Rodentia: Muridae) in New Mexico and Arizona.
AB  - Fecal samples from 3 species of Onychomys (Rodentia: Muridae) captured in New
      Mexico and Arizona were examined for coccidia. Six of the 59 (10%) were infected
      with a new species of Eimeria. Sporulated oocysts (n = 105) of this new species
      are subspheroidal, 17.4 x 16.1 (14-21 x 13-19) microm, with ellipsoidal
      sporocysts 10.4 x 5.7 (9-12 x 5-8) microm. This species occurred in 3 of 24 (13%)
      Onychomys arenicola, 2 of 31 (6%) Onychomys leucogaster from New Mexico, and 1 of
      4 (25%) Onychomys torridus from Arizona. Isolates recovered from O. leucogaster
      and O. torridus were inoculated into O. leucogaster (n = 5) and produced
      infections with a prepatent period of 7 days and a patent period of 7-23 days.

PMID- 9920316
TI  - Two new coccidian parasites from the grand anglehead lizard, Gonocephalus grandis
      from Peninsular Malaysia.
AB  - During 3 collecting expeditions between October 1996 and December 1996, fecal
      samples were obtained from 43 adult Gonocephalus grandis from Tanah Rata and the
      Cameron Highlands in Peninsular Malaysia. Two species of coccidia (Isospora
      gonocephali n. sp. [9/43, 23%] and Eimeria cameronensis n. sp. [3/43, 7%]) were
      discovered. Sporulated oocysts of I. gonocephali are subspherical to ovoidal,
      22.3 x 18.7 (19-25 x 17-23) microm with a bilayered wall composed of a thin inner
      wall and a striated outer wall with a pitted surface; oocyst residuum absent; 1
      polar granule present; sporocysts are almond-shaped, 13.5 x 9.2 (12-15 x 8.5-10)
      microm, Stieda body broad, domelike, substieda body fanlike, sporocyst residuum
      consisting of coarse, nonuniform granules in an amorphous cluster; sporozoites
      sausage-shaped with 1 large terminal, refractile body and lay randomly in the
      sporocyst. Sporulated oocysts of E. cameronensis are bilayered, smooth-walled,
      ellipsoidal, 26.5 x 12.4 (25-28 x 12-13) microm; with 1, small, polar granule
      composed of 2-3 splinter-like structures fused together; oocyst residuum absent;
      sporocysts ovoidal, almost rectangular-shaped 8.8 x 6.6 (8-9 x 5-7) microm, with
      no Stieda or substieda bodies, containing scattered residuum and 2 sausage-shaped
      sporozoites with 1 terminal, ovoidal refractile body. No individual lizard was
      host to both coccidian species.

PMID- 9920317
TI  - Cucullanin nematodes from coral reef fishes of French Polynesia, with a
      description of Cucullanus faliexae n. sp. (Nematoda: Chitwoodchabaudiidae).
AB  - Cucullanus faliexae n. sp. is described from the moray eel Gymnothorax javanicus
      (Muraenidae) collected in Rangiroa (Tuamotu Islands, French Polynesia) in the
      South Pacific and is reported from the same host collected in Moorea (Society
      Islands, French Polynesia). This nematode is distinguished from its congeners by
      its protrubant anus and the presence of a single pair of subdorsal postanal
      papillae. Cucullanus faliexae resembles C. laurotravassosi from which it is
      distinguished by the farther anterior position of the first pair of male caudal
      preanal papillae and by the greater size of its spicules. Cucullanus bourdini
      Petter and Le Bel, 1992 is reported from the coral reef fishes Balistapus
      undulatus (Balistidae), Lutjanus gibbus (Lutjanidae), and Myripristis kuntee
      (Holocentridae) from French Polynesia. Additionally, Cucullanus sp. is reported
      from the coral reef fish Sufflamen bursa (Balistidae) in Moorea and Rangiroa.
      Given that C. faliexae and C. bourdini have been found in widely disparate
      locations between which their definitive hosts cannot migrate, it would seem
      likely that the life cycles of these worms include an intermediate or transport
      host that has a greater capability for dispersal.

PMID- 9920318
TI  - Trebius shiinoi n. sp. (Trebiidae: Siphonostomatoida: Copepoda) from uteri and
      embryos of the Japanese angelshark (Squatina japonica) and the clouded angelshark
      (Squatina nebulosa), and redescription of Trebius longicaudatus.
AB  - Trebius shiinoi n. sp. is described from females and males collected from the
      uterine linings and on embryos within the uteri of 2 near-term Japanese
      angelsharks (Squatina japonica Bleeker, 1858) captured in Suruga Bay, off central
      Japan, and from female specimens reported by Shiino in 1963 that were found on
      embryos of the clouded angelshark (Squatina nebulosa Regan, 1906) captured off
      Shirahama, central Japan. Shiino identified his specimens as Trebius
      longicaudatus Shiino, 1954. However, our comparisons between Shiino's specimens
      and those newly collected revealed both to represent the same species, and
      comparisons of these specimens to 5 syntypes of T. longicaudatus and to published
      information detailing other Trebius species revealed them to be a new species
      that differs most notably from its congeners by the enormous length of its
      transformed adult female's abdomen and by the presence of a distinctive nublike
      seta on her caudal ramus. Trebius shiinoi n. sp. is an unusual copepod because it
      is an endoparasite of adult female angelsharks as well as an ectoparasite of
      embryo angelsharks, and it is proposed that flushing of the uterine-cloacal
      chambers of clouded angelsharks and Japanese angelsharks may facilitate T.
      shiinoi infections. A redescription of T. longicaudatus is also provided.

PMID- 9920319
TI  - Antibody to the Dirofilaria immitis aspartyl protease inhibitor homologue is a
      diagnostic marker for feline heartworm infections.
AB  - Feline heartworm disease, caused by the filarial nematode Dirofilaria immitis,
      has been diagnosed with increased frequency in areas endemic for canine heartworm
      infection. The routine methods for determining the infection status of dogs, such
      as identification of circulating microfilariae in blood or identification of
      circulating antigen in serum, plasma or blood, have proven inadequate for
      screening cats. The inadequacies are due to the likelihood of single-sex
      infections and clinical disease during prepatent infections. Current antibody
      detection methodologies rely on crude or partially purified worm antigen
      preparations that may result in poor specificity. This report describes the
      cloning, expression, and diagnostic utility of the D. immitis homologue (PDi33)
      of the Onchocerca volvulus aspartyl protease inhibitor (Ov33). PDi33 is present
      in all stages that occur in the mammalian host (microfilariae, L3, L4, adult
      males, and females) and is released by adults cultured in vitro. An indirect
      enzyme-linked immunosorbent assay (ELISA) using antibody to recombinant PDi33 as
      a diagnostic marker for infection in cats was very sensitive and was useful for
      identifying prepatent infections. Testing of sera from cats infected with common
      gastrointestinal parasites also indicated excellent specificity. The same ELISA
      in dogs, although demonstrating reasonable sensitivity and specificity, appeared
      to be of less value as compared with the currently accepted antigen detection
      methodologies.

PMID- 9920320
TI  - Species-specificity and sensitivity of a PCR-based assay for Perkinsus marinus in
      the eastern oyster, Crassostrea virginica: a comparison with the fluid
      thioglycollate assay.
AB  - We examined the species-specificity and sensitivity of a polymerase chain
      reaction (PCR)-based assay for Perkinsus marinus and compared its overall
      performance with the fluid thioglycollate medium (FTM) assay on oyster
      (Crassostrea virginica) hemolymph, mantle, and rectum samples. Our results
      indicated that the PCR-based methodology is species-specific because Perkinsus
      olseni, Perkinsus atlanticus, and Perkinsus spp. DNAs were not amplified with the
      PCR primers developed for P. marinus diagnosis. The sensitivity of the PCR
      method, as assessed through spike/recovery experiments, was established by the
      detection of as few as 1 cell of P. marinus in 30 mg of oyster tissue. Tissue
      samples from naturally infected oysters analyzed both by the FTM and PCR assay
      suggested that the latter was more sensitive for the diagnosis of P. marinus.
      Positive results for P. marinus infection ranged from 70% to 83% by FTM and from
      92% to 100% by PCR, depending on the tissue examined. Therefore, species
      specificity and sensitivity of the NTS-based PCR assay validate its use as a tool
      for assessment of P. marinus in mollusks.

PMID- 9920321
TI  - Diagnosis of trypanosomiasis in experimental mice and field-infected camels by
      detection of antibody to trypanosome tyrosine aminotransferase.
AB  - Sera from animals with acute and chronic Trypansoma evansi infections were
      examined directly for trypanosome tyrosine aminotransferase activity and
      indirectly for their ability to inhibit tyrosine aminotransferase activity. It
      was shown that sera from acutely infected mice and camels with high parasitemias
      contained significant levels of trypanosome tyrosine aminotransferase activity.
      In contrast, the sera from chronically infected mice and camels did not contain
      significant tyrosine aminotransferase activity, but they were able to neutralize
      the enzyme activity in trypanosome homogenates. The sera from camels with other
      pathological conditions did not neutralize this enzyme activity. It is suggested
      that the inhibitory factor in the chronic sera is antibody. The potential use of
      the direct enzyme assay and the indirect neutralization assay as diagnostic tools
      are discussed. Finally, the use of these assays to distinguish between early
      (acute) and late (chronic) infections are also suggested.

PMID- 9920322
TI  - Permissiveness of human monocytes and monocyte-derived macrophages to infection
      by promastigotes of Leishmania (Viannia) panamensis.
AB  - During natural infections, Leishmania is in contact with a variety of mononuclear
      phagocytic cells in different tissues, including resident macrophages and
      monocytes mobilized to the site of infection from the bone marrow and blood
      circulation. Because the functional capabilities of fully differentiated
      macrophages and blood monocytes differ, the outcome of infection by Leishmania
      may depend upon the stage of differentiation of the host cells. To address this
      question, we evaluated Leishmania panamensis infection of (1) the human
      promonocytic/histiocytic cell line U-937 before and after induction of
      differentiation by phorbol myristate acetate; (2) fresh human peripheral blood
      monocytes; and (3) macrophages derived from monocytes by differentiation in
      vitro. Based on the percentage of cells infected and the number of parasites per
      cell, macrophages derived from monocytes or by induction of differentiation of U
      937 cells were significantly more permissive to infection by stationary-phase L.
      (Viannia) panamensis promastigotes than monocytes. Increasing time and maturation
      in culture prior to exposure to infective promastigotes was associated with the
      increased permissiveness of differentiated macrophages to infection (P<0.05). The
      percentage of cells infected and number of amastigotes per cell increased with
      time postinfection for both monocytes and macrophages but remained significantly
      greater for macrophages. The increased expression of CD68, CD16, and lysozyme,
      and decreased expression of peroxidase by macrophages cultured for 5 days in
      vitro compared with fresh monocytes, whether adherent or in suspension, supported
      the distinct maturation status of these cells.

PMID- 9920323
TI  - Unusual transmission of the liver fluke, Fasciola hepatica, by Lymnaea glabra or
      Planorbis leucostoma in France.
AB  - Cases of fasciolosis in ruminants have been recorded in several French farms in
      the absence of Lymnaea truncatula, which is considered the only snail
      intermediate host in western Europe. These farms harbored other species of
      freshwater snails in large numbers (Lymnaea glabra, Physa acuta, or Planorbis
      leucostoma) and, in many cases, had cattle or sheep infected by another trematode
      (Paramphistomum daubneyi). These other freshwater snails may serve as
      intermediate hosts for F. hepatica due to a coexisting infection with P.
      daubneyi. We have demonstrated that L. glabra, either infected with F. hepatica
      alone or coinfected by P. daubneyi, was capable of developing a F. hepatica
      infection. A broader range of L. glabra size classes (up to 10 mm in height) were
      susceptible to infection if simultaneously infected with P. daubneyi. Planorbis
      leucostoma can only serve as an intermediate host for F. hepatica, if infected
      with P. daubneyi. Lastly, P. acuta smaller than 4 mm cannot serve as an
      intermediate host. These results may explain, in part, the maintenance of low
      level F. hepatica infections in the absence of the normal intermediate host, L.
      truncatula.

PMID- 9920324
TI  - A digenean metacercaria from the reef coral, Porites compressa, experimentally
      identified as Podocotyloides stenometra.
AB  - Feeding Porites compressa infected with a digenean metacercaria to the coral
      feeding butterflyfish, Chaetodon multicinctus, established that the metacercaria
      was Podocotyloides stenometra. Those and field examinations finding a prevalence
      of 100% and an average intensity of infection of 6.5 worms/fish in 28 C.
      multicinctus off Kaneohe Bay, Oahu, Hawaii, established this fish as a definitive
      host. Plagioporus sp. of Cheng and Wong, 1974 is a synonym of P. stenometra.

PMID- 9920325
TI  - Maintenance of Acanthamoeba culbertsoni by cryopreservation.
AB  - In order to determine the viability of trophozoites of Acanthamoeba culbertsoni
      under cryopreservation conditions, cultures in serum-casein-glucose-yeast extract
      medium were subject to 5%, 7.5%, and 10% concentrations of dimethylsulfoxide
      (DMSO). With the methodology followed, the percentages of recovery varied between
      75.6% and 86.6% with DMSO at 10%, between 54.5% and 73.5% with DMSO at 7.5%, and
      between 43.6% and 68.5% with DMSO at 5%. The amebae were kept in liquid nitrogen
      for 30-210 days. The highest viability of trophozoites was founded when DMSO was
      used at a final concentration of 10% and an equilibrium temperature of 4 C. Gross
      cultural or morphological changes were not noted in trophozoites thawed from
      frozen suspensions.

PMID- 9920326
TI  - Anthelmintic efficacy against tissue-arrested larvae of Ancylostoma caninum in
      murine hosts.
AB  - Third-stage larvae of the major human and canine Ancylostoma hookworm species
      have the capacity to undergo developmental arrest in the somatic tissues of an
      infected host. Arrested larvae reactivate at opportune periods such as pregnancy,
      which results in the transmammary transmission of infection to the nursing
      neonates. Using murine paratenic hosts to focus specifically on tissue-arrested
      stages of Ancylostoma caninum, the present study found that neither recommended
      nor elevated doses of commonly used anthelmintics were effective in eliminating
      latent infections at the accepted standard of greater than 90% reduction in
      parasite burden. Of the drugs tested, i.e., pyrantel, fenbendazole, ivermectin,
      and milbemycin, ivermectin was the most effective and engendered an 80% reduction
      in the burden of tissue-arrested A. caninum larvae but only if administered
      repeatedly or at elevated doses. Studies in 2 inbred mouse strains, BALB/c (H-2b)
      and C57BL/6 (H-2d), that typically display divergent immune responses to various
      infections showed no significant differences in the efficacies of the drugs
      tested. The results of this study indicate that there is still a need for
      effective strategies of eradicating latent infections with tissue-arrested
      hookworm larvae.

PMID- 9920327
TI  - Improved culture media for piscine hemoflagellates, Cryptobia and Trypanosoma
      (Kinetoplastida).
AB  - Increasing the Hepes buffer in minimum essential medium from 25 mM to 100 mM
      yielded a significantly larger number of Cryptobia salmositica. Cryptobia
      salmositica (pathogenic and nonpathogenic strains), Cryptobia bullocki, and
      Trypanosoma danilewskyi did not multiply either in heat-inactivated trout plasma
      (< or =25%) or in less than 10% fresh trout plasma. Both strains of C.
      salmositica multiplied better in 10% fresh trout plasma than in 25% heat
      inactivated fetal bovine serum. In contrast, C. bullocki and T. danilewskyi
      multiplied better in 25% fetal bovine serum; 10% fetal bovine serum did not
      significantly reduce multiplication of C. bullocki. The nonpathogenic vaccine
      strain of C. salmositica cultured in 10% fresh trout plasma still protected
      rainbow trout from high parasitemia when challenged with the pathogen.

PMID- 9920328
TI  - New host and ocean records for the copepod Ommatokoita elongata
      (Siphonostomatoida: Lernaeopodidae), a parasite of the eyes of sleeper sharks.
AB  - Seven of 8 Pacific sleeper sharks (Somniosus pacificus Bigelow and Schroeder,
      1944) captured in Prince William Sound, Alaska, were actively infected, and all 8
      had been at one time infected with the parasitic copepod Ommatokoita elongata
      (Grant, 1827) (Siphonostomatoida: Lernaeopodidae). Active infections consisted of
      adult females and chalimus larvae that had attached to the corneas of the sharks'
      eyes. This report documents a new host record and possibly the only reliable
      record of this parasite from a host other than the Greenland shark, Somniosus
      microcephalus (Bloch and Schneider, 1801). It also documents the first time O.
      elongata has been identified outside of the Atlantic Ocean or its locally
      adjacent straits and seas.

PMID- 9920329
TI  - Beneficial effect of selenium supplementation during murine infection with
      Trypanosoma cruzi.
AB  - Selenium (Se) has been shown to function as an antioxidant that may enhance
      immunity during microbial infection. To investigate the effect of elevated levels
      of Se on the course of experimental Chagas' disease, 5 groups of C3HeB/FeJ mice
      were infected with 10(3) bloodform trypomastigotes of a Brazil strain of
      Trypanosoma cruzi while receiving supplements of 0 ppm, 2 ppm, 4 ppm, 8 ppm, or
      16 ppm Se as sodium selenate in drinking water. After 64 days of infection,
      survival ranged from 0 to 60%, with groups receiving 4 ppm and 8 ppm Se
      exhibiting 60% survival and the group without Se exhibiting 0% survival. In
      addition, parasitemia levels of mice supplemented with Se were significantly
      lower (P<0.01) than in nonsupplemented mice. The results of the present study
      suggest that Se supplementation does have a beneficial effect during murine
      infection with T. cruzi, resulting in decreased parasitemias and increased
      longevity.

PMID- 9920330
TI  - Endocotyle bushi (Trematoda: Microphallidae) from willets, Catoptrophorus
      semipalmatus from Galveston, Texas.
AB  - During a study of Digenea of shorebirds from Galveston, Texas, 30% (30 of 99) of
      willets, Catoptrophorus semipalmatus (Charadriiformes), were found to be infected
      with 55-405 Endocotyle bushi per infected host. Although the specimens from Texas
      generally agree with E. bushi from Florida, specimens from Texas are less
      elongated, have a more triangular to heart-shaped ovary, have slightly larger
      eggs, and have a smaller seminal vesicle.

PMID- 9920331
TI  - Comparative infectivity of Toxoplasma gondii bradyzoites in rats and mice.
AB  - Infectivity of Toxoplasma gondii bradyzoites was compared in outbred female
      Sprague Dawley rats and outbred Swiss Webster mice. Rats inoculated
      subcutaneously with 1-10 bradyzoites of the 2 strains of T. gondii (VEG and GT-1)
      developed persistent infection, whereas an infective dose by the oral route was
      10-1,000 bradyzoites. The infectivity of bradyzoites of the VEG and the GT-1
      strains of T. gondii in rats by the subcutaneous route was comparable to that in
      mice.

PMID- 9920332
TI  - Egg production capacity of Paragonimus pulmonalis in cats.
AB  - In the present study, each of 43 cats was fed with a single metacercaria of
      Paragonimus pulmonalis and 2 cats (controls) with 2 metacercariae. They were
      killed 22-372 days postinfection. In the test group, 18 (41.9%) cats were
      infected, as well as the 2 cats in the control group. Among the 18 worms
      recovered from the test group, 9 found in the lungs were mature, whereas 5 mature
      and 4 immature worms were in the pleural cavity. Most eggs from worms encased in
      a cyst were passed in the feces. However, eggs from worms in the pleural cavity
      were only found on the lung surface and pleural cavity. Mature worms in cysts
      seemed to exhibit higher egg production capacity than those in the pleural
      cavity. Paired mature worms from a cyst laid more eggs than a single encysted
      mature worm in vitro at room temperature.

PMID- 9920333
TI  - Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple
      clone Plasmodium falciparum infections in northern Tanzania.
AB  - Allelic diversity in the merozoite surface protein-1 (MSP-1) of Plasmodium
      falciparum, a major malaria vaccine candidate, was examined in clinical isolates
      from holoendemic northern Tanzania. The variable blocks 2, 4a, 4b, 6, and 10 of
      the MSP-1 gene were typed by allelic type-specific polymerase chain reaction.
      Twenty-four possible MSP-1 gene types were defined as unique combinations of
      allelic types detected in each variable block. Thirteen gene types were
      identified, and 187 P. falciparum populations were fully typed among 79 isolates.
      In contrast with recent findings in Vietnam, we were unable to detect nonrandom
      associations between allelic types in the typed variable blocks. Most patients
      (60%) harbored more than 1 genetically distinct parasite population (average:
      2.37 populations per isolate) and, in 1 patient, 6 different versions of this
      single-copy gene were found. Statistical analysis suggests that parasites
      carrying different MSP-1 gene types are not independently distributed in the host
      population. The epidemiological consequences of these findings are discussed.

PMID- 9920334
TI  - Influence of rat strain on larval production by the parasitic nematode
      Strongyloides ratti.
AB  - The course of infection with Strongyloides ratti in a range of rat strains was
      assessed by monitoring the production of larvae. To our knowledge, this is the
      first such study of S. ratti using its natural host Rattus norvegicus. Host
      strain influenced the pattern of larval production. The results were
      qualitatively the same for 2 S. ratti lines of North American and Japanese
      origin.

PMID- 9920335
TI  - Helminths of six species of Anolis lizards (Polychrotidae) from Hispaniola, West
      Indies.
AB  - From Hispaniola, an island in the West Indies, 6 species of anoles, Anolis
      cristatellus, Anolis etheridgei, Anolis eugenegrahami, Anolis hendersoni, Anolis
      monticola, and Anolis olssoni were examined for helminths. Helminths representing
      2 species of trematodes, Mesocoelium monas and Urotrema scabridum; 1 species of
      cestode, Oochoristica maccoyi; 11 species of nematodes, Atractis scelopori,
      Oswaldocruzia lenteixeirai, Parapharyngodon cubensis, Skrjabinoptera
      leiocephalorum, Trichospirura teixeirai, Ascarops sp., Physocephalus sp.,
      Porrocaecum sp., Rhabdias sp., Acuariidae gen. sp. and Cosmocercidae gen. sp.;
      and 1 species of acanthocephalan, Centrorhynchus sp., were found. Skrjabinoptera
      leiocephalorum, Ascarops sp., and Physocephalus sp. from A. cristatellus and all
      helminths recovered from the other 5 anole species represent new host records.

PMID- 9920336
TI  - Gastrointestinal helminths of four gekkonid lizards, Gehyra mutilata, Gehyra
      oceanica, Hemidactylus frenatus and Lepidodactylus lugubris from the Mariana
      Islands, Micronesia.
AB  - The gastrointestinal tracts of gekkonid lizards from Guam (Gehyra mutilata [n =
      4], Gehyra oceanica [n = 11], Hemidactylus frenatus [n = 43], and Lepidodactylus
      lugubris [n = 38]) and Rota (Gehyra oceanica [n = 2], Hemidactylus frenatus [n =
      13], and Lepidodactylus lugubris [N = 20] were examined for helminths. Found were
      2 species of cestodes, Cylindrotaenia allisonae, Oochoristica javaensis, 1
      species of trematode, Allopharynx macallisteri, and 5 species of nematodes,
      Pharyngodon lepidodactylus, Spauligodon gehyrae, Spauligodon hemidactylus,
      Skrjabinelazia machidai, Oswaldocruzia sp. New host records included Gehyra
      mutilata for Spauligodon hemidactylus, Gehyra oceanica for Oochoristica
      javaensis, Hemidactylus frenatus for Skrjabinelazia machidai, and Lepidodactylus
      lugubris for Cylindrotaenia allisonae and Oswaldocruzia sp. These helminths are
      known only from Pacific Islands and the Australian biogeographic realm.

PMID- 9920337
TI  - Multiple Cryptosporidium serpentis oocyst isolates from captive snakes are not
      transmissible to amphibians.
AB  - Viable Cryptosporidium serpentis oocysts originating from 6 captive snakes were
      gastrically delivered to 12 Cryptosporidium-free African clawed frogs and 9
      tadpoles and 3 recently metamorphosed adults of Cryptosporidium-free wood frogs.
      On days 7 and 14 postinoculation, no life-cycle stage of Cryptosporidium was
      observed in any of the histological sections of stomach, jejunum, ileum, cloaca,
      and cecum. However, viable inoculum-derived C. serpentis oocysts were recovered
      from the water in which the amphibians were kept. Amphibians may disseminate C.
      serpentis oocysts in the natural habitat.

PMID- 9920338
TI  - Blood parasites of shrews from Pennsylvania.
AB  - We examined 30 Sorex cinereus, 5 Sorex fumeus, and 21 Blarina brevicauda
      collected from Pennsylvania in 1995 for blood parasites. Trypomastigotes of
      Trypanosoma sp. were visible in 13% of the S. cinereus. Ten percent of S.
      cinereus, 20% of S. fumeus, and 14% of B. brevicauda were infected with
      Bartonella sp. (or spp.). In S. cinereus, we detected no concurrent Trypanosoma
      and Bartonella infections.

PMID- 9920339
TI  - First records of Hyalomma aegyptium (Acari: Ixodida: Ixodidae) from the Russian
      spur-thighed tortoise, Testudo graeca nikolskii, with an analysis of tick
      population dynamics.
AB  - During the fall of 1995 and the spring of 1996, 77 statistically comparable tick
      collections, comprising 792 specimens, were made from adults of the Russian spur
      thighed tortoise, Testudo graeca nikolskii, at 4 sites along Russia's Black Sea
      coast. These are the first tick collections reported from T. g. nikolskii since
      its recognition as a taxonomic entity. All ticks were determined to be Hyalomma
      (Hyalomma) aegyptium, a common tortoise parasite in southern Russia that in 1930
      was erroneously designated the type of subgenus Hyalommasta. Male ticks were
      recovered from more tortoises (67) than were females (57) or immatures (14), and
      nymphs were seen only in the fall. Significantly more ticks parasitized male
      tortoises than females, perhaps because males of T. g. nikolskii have larger home
      ranges. However, no functional relationship was found between tortoise ventral
      surface area and degree of tick infestation. Like other tortoise ticks, H.
      aegyptium is expected to decline in concert with its increasingly threatened
      hosts.

PMID- 9920340
TI  - Hookworms (Uncinaria sp.) in Juan Fernandez fur seal pups (Arctocephalus
      philippii) from Alejandro Selkirk Island, Chile.
AB  - Sixty Juan Fernandez fur seal pups (Arctocephalus philippii) found dead on
      Alejandro Selkirk Island, Chile, during the breeding seasons of 1991 and 1992
      were examined for the presence of hookworms (Uncinaria sp.). Hookworms were found
      in 60% of the pups examined, at a mean intensity of 17 parasites per infected
      host. Intensity of infection did not differ among years or sexes. There was a
      significant positive relationship between thickness of subcutaneous fat and
      number of hookworms.

PMID- 9920341
TI  - Identification of genes encoding Schistosoma mansoni antigens using an antigenic
      sequence tag strategy.
AB  - Another approach for the identification of genes that code for antigenic products
      is described using an antigenic sequence tag (AST) strategy. A Schistosoma
      mansoni adult worm cDNA library was screened with affinity chromatography
      purified immunoglobulins from infected human sera and a mild oxidation treatment
      with sodium periodate. From 1 or both ends of 30 cDNA clones, 30 ASTs were
      obtained. Of these, 22 were previously known Sm antigens. One clone had matches
      with entries for other organisms in the databases and 6 had homology with Sm
      expressed sequence tags (EST) entries. These clones, together with another 1 that
      had no significant database matches, were considered new antigenic genes in S.
      mansoni. The strategy proved to be efficient for the identification of genes that
      could be used for immunological studies and evaluation as vaccine candidates.

PMID- 9920342
TI  - Do changes in the hydration of the diabetic human lens precede cataract
      formation?
AB  - Cataract formation in diabetic lenses has been attributed to polyol-osmotic
      pressure-generated influx of water. The ensuing swelling in the form of pocket
      and lake accumulations cause light scattering. The authors tested whether clear
      lenses of diabetic patients show different hydration properties than age matched
      normal lenses. Normal and diabetic human lenses were investigated for their
      nonfreezable water content by differential scanning calorimetry. The total water
      content of the lens sections were studied by thermogravimetric analysis. Non
      cataractous diabetic lenses in all three regions showed a higher total water
      content than normal lenses. The nonfreezable water content, seems to increase
      with age in diabetic lenses and decrease with age in normal human lenses. Thus,
      hydration changes in human diabetic lenses precede cataract formation. While
      syneresis, the release of bound water into the bulk, is part of the normal aging
      process, it appears to occur in the younger diabetics only. In older diabetics
      syneresis is halted or even reversed. This may be due to the glycation of lens
      proteins in diabetic patients which tends to immobilize water and therefore,
      reverse the syneresis due to aging.

PMID- 9920343
TI  - Effect of selected substances on heat-induced aggregation of albumin, IgG and
      lysozyme.
AB  - Compounds capable of inhibiting protein aggregation may find pharmacological
      applications in the treatment of a number of diseases called protein condensation
      diseases [Benedek (1997)], which include cataract, biliary and urinary lithiasis
      and certain rheumatic diseases. We examined the effect of selected compounds on
      heat-induced aggregation human serum albumin (HSA), IgG and lysozyme. HSA (0.2%
      w/v in 0.066 M sodium phosphate pH 5.3 at 22 degrees C), IgG (0.5% w/v in 0.066 M
      Tris pH 8.0 at 22 degrees C), and L (0.2 % w/v in 0.066 M CAPS pH 11.0 at 22
      degrees C) were heated for 30 min at 70 degrees C in the presence or absence of
      different concentrations of the substance under examination and heat-induced
      aggregation of 100 microl aliquots was evaluated by measuring the absorbance at
      595 nm using an automatic microplate reader. In these conditions, inhibition of
      aggregation could be due to an anti-denaturant effect or to interferences with
      the aggregation of denatured molecules, as previously described [Saso, Casini et
      al. (1998)]. However, this distinction may not be pharmacologically relevant when
      the target of the therapy is the prevention of abnormal phenomena of protein
      aggregation. Inorganic salts like NaCl and CaCl2 were active on the three
      proteins (IgG > HSA > L) but many ligands of HSA such as tryptophan, N-acetyl
      tryptophan, caprylic acid, capric acid, cholic acid, deoxycholic acid,
      chenodeoxycholic acid, lithocholic acid and bendazac were active on their carrier
      but not on IgG and L, indicating that the latter proteins are more difficult to
      protect and that specific anti-denaturant and/or anti-aggregant compounds should
      be developed.

PMID- 9920344
TI  - Effect of docosahexaenoic acid on intracellular calcium dynamics in vascular
      smooth muscle cells from normotensive and genetically hypertensive rats.
AB  - The effects of DHA treatment on intracellular Ca2+ dynamics in aortic smooth
      muscle cells isolated from young stroke-prone spontaneously hypertensive rats
      (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated.
      The resting intracellular Ca2+ concentration ([Ca2+]i) before stimulation and the
      peak [Ca2+]i induced by 5-HT, angiotensin II and depolarizing concentration of
      KC1 were higher in SHRSP than in WKY. When added to the culture medium for 2
      days, DHA at a concentration of 30 microM significantly suppressed the peak
      [Ca2+]i induced by these stimulants in aortic smooth muscle cells isolated from
      WKY, whereas smooth muscle cells of SHRSP were refractory to the suppression. DHA
      had no suppressive effect on the 5-HT-induced increase in the inositol
      triphosphate production. The present study indicates that DHA can suppress
      receptor-mediated Ca2+ influx, at least, through the voltage-dependent channel,
      in vascular smooth muscle cells. Since the intracellular Ca2+ plays an important
      role in regulating vascular tone, the suppressive effect of DHA on [Ca2+]i in
      vascular smooth muscle cells may be contributed to the beneficial properties of
      DHA on cardiovascular disorders. The precise mechanisms of action remain to be
      elucidated.

PMID- 9920345
TI  - Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after
      intravenous and oral administration to rats with uranyl nitrate-induced acute
      renal failure.
AB  - Because the physiological changes that occur in patients with acute renal failure
      could alter the pharmacokinetics of the drugs used to treat the disease, the
      pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were
      investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg)
      administration to control rats and rats with uranyl nitrate-induced acute renal
      failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on
      the basis of physiological parameters. After intravenous administration of YJA
      20379-8, the pharmacokinetic parameters were not significantly different between
      two groups of rats except significant increase in volume of distribution at
      steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral
      administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126
      versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8
      from gastrointestinal tract; the percentages of oral dose of YJA-20379-8
      recovered from gastrointestinal tract at 24 hr as unchanged drug was
      significantly greater (19.9% versus 6.61%) in rats with U-ARF.

PMID- 9920346
TI  - The cytochrome P450 suicide inhibitor, 1-aminobenzotriazole, sensitizes rats to
      zymosan-induced toxicity.
AB  - Reduction in whole body cytochrome P450 (CYP 450) activity is evident in humans
      who develop trauma and sepsis-induced multiple organ failure (MOF). It is not
      known whether this has any deleterious or protective effect. Intraperitoneal
      injection of zymosan, the cell wall of Saccharomycoses A, induces dose-dependent
      inflammation with concomitant MOF in rats. High dose intraperitoneal zymosan (100
      mg/100 g body weight) causes mortality and organomegaly in rats; low dose zymosan
      (20 mg/100 g body weight) does not. To study a role for CYP 450 in zymosan
      induced toxicity, we examined the effect of the non-specific CYP 450 suicide
      inhibitor 1-aminobenzotriazole (1-ABT)(80 mg/kg/d), on rats treated with low dose
      zymosan. The 90% reduction in CYP 450 content achieved by this dose of 1-ABT was
      associated with 58% mortality in rats treated with low dose zymosan, in contrast
      to no mortality in rats treated with low dose zymosan alone (p < 0.01). In
      survivors, liver and lung organomegaly (p < 0.01), and polymorphonuclear
      leukocyte accumulation in the liver (p < 0.01) were increased after zymosan
      administration in rats treated with 1-ABT compared to those without 1-ABT. There
      was no effect of treatment with 1-ABT on the increased urinary excretion of
      nitric oxide byproducts observed after zymosan administration. These observations
      are consistent with the hypothesis that the CYP 450 enzyme system is an
      endogenous protectant in this experimental model of inflammation-induced MOF.

PMID- 9920347
TI  - 2-(allylthio)pyrazine inhibition of aflatoxin B1-induced hepatotoxicity in rats:
      inhibition of cytochrome P450 2B- and 3A2-mediated bioactivation.
AB  - 2-(Allylthio)pyrazine (2-AP), a synthetic organosulfur compound, exhibits
      hepatoprotective and chemopreventive effects. The effects of 2-AP on aflatoxin B1
      (AFB1)-induced hepatotoxicity was studied in rats. 2-AP treatment substantially
      reduced AFB1-induced toxicity, as evidenced by reduction in the mortality rate of
      animals as well as decreases in serum alanine aminotransferase and sorbitol
      dehydrogenase activities. AFB -induced lipid peroxidation was also significantly
      reduced in rats by 2-AP treatment. Studies were extended to determine whether 2
      AP was active in inhibiting cytochrome P450-mediated metabolic activation of
      AFB1. Covalent binding of AFB1 to calf thymus DNA in the presence of S-9 fraction
      was inhibited by 2-AP in vitro. Hepatic microsomal pentoxyresorufin-O-depentylase
      and ethoxyresorufin-O-deethylase activities were also potently inhibited by 2-AP.
      These results demonstrated that 2-AP was effective in protecting the liver
      against AFB1-induced toxicity and the mechanism of chemoprotection by 2-AP might
      involve inhibition of the P450 2B- and 3A2-mediated metabolism of AFB1.

PMID- 9920348
TI  - Changes in cytosolic Ca2+ measured by use of fura-2 and contraction produced by
      quick stretch and various stimulants in canine cerebral artery.
AB  - Mechanical stimulation such as stretch generates myogenic contraction in cerebral
      arteries. Myogenic contraction of cerebral arteries in response to quick stretch
      is greatly modified by promoters and inhibitors of Ca2+ handling mechanisms
      including Ca2+ channel blockers. In the present study, in order to improve our
      understanding of the role of Ca2+ in the generation of stretch-induced
      contraction, changes in cytosolic free Ca2+ concentrations ([Ca2+]cyt) and
      contraction of canine cerebral artery in response to quick stretch were
      simultaneously measured by use of fura-2. The [Ca2+]cyt-tension relationship in
      the stretch-induced contraction was compared with those by various stimulants.
      Quick stretch at a rate of 10 cm/sec with the amount of 40% of the initial muscle
      length (=100%) produced a myogenic contraction in canine cerebral artery. The
      arterial [Ca2+]cyt enormously increased after the stretch, which preceded the
      occurrence of the delayed contraction in response to stretch. [Ca2+]cyt-tension
      relationships in the stretch-induced contraction changed counterclockwise as
      those in the contractions induced by high KC1 and pharmacological agonistic
      stimulants such as 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1). The
      contraction in response to quick stretch at the maintenance phase was far smaller
      than those produced by high KC1 or agonistic stimulants at the same changes in
      [Ca2+]cyt. These findings suggest that in the cerebral artery contraction in
      response to quick stretch, elevated cytosolic Ca2+ is utilized less efficiently
      as compared with the contractions elicited by other stimulants. The apparent low
      Ca2+ sensitivity of stretch-induced contraction in dog cerebral artery might be
      related to the low efficiency of cytosolic Ca2+ elevated by the Ca2+ release from
      intracellular storage sites upon stretch.

PMID- 9920349
TI  - Fas receptor expression on asthmatic eosinophils.
AB  - Activation of the Fas receptor (Fas; CD95) on eosinophils induces apoptosis and
      may play a role in controlling eosinophil number in blood and tissue. To
      determine whether Fas expression on eosinophils is different between asthmatics
      and non-asthmatics, eosinophils were isolated from the peripheral blood using a
      three-step procedure of dextran sedimentation, ficoll hypaque separation and
      negative selection with anti-CD16 monoclonal antibody bound to magnetic beads.
      Fas expression was quantified by flow cytometry. Fas expression and the
      percentage of eosinophils expressing Fas were not different between asthmatics
      (n=9) and non-asthmatics (n=14).

PMID- 9920350
TI  - Complement and atherogenesis: the unknown connection.
AB  - The question why low-density lipoprotein (LDL) stranded in the subendothelium of
      arteries should acquire the proinflammatory properties that initiate and sustain
      atherogenesis has puzzled researchers for decades. The most popular concept
      contends that oxidative processes are crucial because oxidized LDL (ox-LDL)
      produced in vitro has atherogenic properties and small amounts of it are found in
      atherosclerotic lesions. Recently, a possible role for vascular infections has
      also been considered because infectious agents, in particular Chlamydia
      pneumoniae, are sometimes present in the lesions. Here, evidence is summarized
      for a different concept of atherogenesis, which evolves from the fact that
      nonoxidative, enzymatic degradation of LDL transforms the lipoprotein to an
      atherogenic moiety. Our group proposes that enzymatically degraded LDL (E-LDL)
      initiates and sustains atherosclerosis through its capacity to activate
      complement and macrophages. These processes are initially meaningful because they
      enable the stranded lipoprotein to be removed from the vessel wall, but they
      become harmful when the cholesterol removal system is overloaded. A novel type of
      chronic inflammation then ensues producing the characteristic pathology of the
      atherosclerotic lesion.

PMID- 9920351
TI  - Neuropeptide Y: a novel link between the neuroendocrine system and cholesterol
      metabolism.
AB  - High serum total and low-density lipoprotein (LDL) cholesterol levels constitute
      the main risk factor for atherosclerotic vascular diseases. Both genetic and
      environmental factors are involved in the regulation of serum cholesterol levels.
      Neuropeptide Y (NPY), which is widely expressed in both the central and
      peripheral nervous systems, is known to regulate food intake and energy balance
      but its role in cholesterol metabolism has remained almost untouched in former
      literature. A newly discovered association between a leucine(7)-to-proline(7)
      polymorphism (Pro(7)) in the signal peptide of NPY and a high cholesterol level
      may provide new ideas for the genetic regulation of cholesterol metabolism. The
      presence of the Pro(7) in NPY results in serum total cholesterol levels 0.6-1.4
      mmol/L higher compared with subjects without this gene variant. The Pro(7) in NPY
      was detected in 14% of Finns but only in 6% of Dutchmen, and its impact on serum
      cholesterol concentration seems to be stronger in obese than in normal-weight
      subjects. At least among Finns, the Pro(7) in NPY is one of the strongest genetic
      factors identified thus far affecting serum cholesterol levels.

PMID- 9920352
TI  - Effects of sex steroids on proliferation in normal mammary tissue.
AB  - Numerous women are treated with a combination of oestrogen and progestogen for
      contraception and hormone replacement therapy worldwide. A possible increased
      risk of cancer in target organs has been discussed vividly for many years. While
      oestrogens are clearly mitogenic for breast epithelial cells, there has been
      considerable uncertainty about the effects of progestogens. This article reviews
      current knowledge on this field, including our own data. Oestrogen receptors are
      down-regulated during the luteal phase, while progesterone receptors remain at a
      high level throughout the menstrual cycle. According to most studies, in vivo
      proliferation of normal breast epithelial cells is higher during the luteal phase
      in the vast majority of women. Normal breast tissue can convert oestrone sulphate
      to oestradiol. A negative correlation between the levels of circulating
      oestradiol and the enzyme converting oestrone into oestradiol suggests a local
      regulatory mechanism of tissue oestradiol formation. Serum progesterone levels
      correlate positively with sulphatase activity while 19-norsteroid progestogens
      may be inhibitory. We found that long-term continuous combined hormonal treatment
      with conjugated equine oestrogens and medroxyprogesterone acetate induced a
      proliferative response in the breasts of surgically postmenopausal macaques. The
      effect of combined treatment was more pronounced than that of oestrogen treatment
      alone. Both endogenous progesterone and exogenous progestogens increase
      proliferation of breast epithelial cells. Exogenous progestogens down-regulate
      both oestrogen and progesterone receptors. Oestrogen and progestogens may have
      both direct and indirect stimulating effects on proliferation. The finding of a
      positive correlation between insulin-like growth factor I messenger RNA and
      proliferation found in hormonally treated women with low receptor levels suggests
      the possibility of nonreceptor-mediated effects of sex steroids on proliferation,
      which needs to be investigated further.

PMID- 9920354
TI  - Rhinoviruses: important respiratory pathogens.
AB  - The most frequent viruses associated with respiratory infections are human
      rhinoviruses (HRVs). Although the majority of HRV infections are mild and self
      limited, HRV is an important cause of respiratory disease across all age groups.
      Recent studies using reverse transcriptase polymerase chain reaction to detect
      HRV genomes have established the importance of HRVs in predisposing to or causing
      otitis media, sinusitis and exacerbations of asthma, as well as other lower
      respiratory tract disorders. Among elderly people, infants and immunocompromised
      hosts HRV infections are often associated with lower respiratory tract morbidity
      and rarely mortality. How often active viral replication occurs in the middle
      ear, sinuses or the lower respiratory tract remains to be determined. However,
      the high incidence of HRV infections and their frequent association with upper
      and lower respiratory tract complications highlight the need for more effective
      means of prevention and treatment.

PMID- 9920353
TI  - Ovarian cancer in infertility patients.
AB  - The possibility that ovulation induction increases the risk of ovarian cancer
      remains unproven. However, recent studies suggest that both infertility and
      endometriosis may be independent risk factors. Despite the various case reports
      and epidemiological studies performed the association between the use of
      infertility drugs and ovarian cancer remains weak. The fact that the women who
      were the first to use ovulation agents are now reaching mid-life means that
      future studies should show whether any association exists. Hence, there is a need
      now for large prospective trials to be performed to establish whether an
      association between ovulation induction agents and ovarian cancer truly exists.

PMID- 9920356
TI  - Increased tendency towards gingival bleeding caused by joint effect of alpha
      tocopherol supplementation and acetylsalicylic acid.
AB  - Alpha-tocopherol (vitamin E) may play a role in the treatment of arterial
      thromboembolic disease, possibly by inhibiting platelet aggregation. Thus far, no
      clinical evidence exists for this effect. The objective of this study was to
      assess the effect of alpha-tocopherol supplementation on gingival bleeding either
      in combination with acetylsalicylic acid (ASA) or without it. This study was an
      end-point examination of a random sample of male smokers who had participated in
      a controlled clinical trial, the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention Study (ATBC Study) for 5-7 years. The study included 409 men aged 55
      74 years of whom 191 received alpha-tocopherol supplementation (50 mg/day); 56
      used ASA, 30 received both and 132 received neither. Gingival bleeding was
      examined by probing with a WHO probe and reported as a percentage of bleeding
      sites adjusted by the logistic regression model. Gingival bleeding was more
      common in those who received alpha-tocopherol compared with nonreceivers among
      subjects with a high prevalence of dental plaque (P < 0.05). ASA alone increased
      bleeding only slightly. The highest risk of gingival bleeding was among those who
      took both alpha-tocopherol and ASA (33.4% of probed sites bleeding vs 25.8% among
      subjects taking neither alpha-tocopherol nor ASA, P < 0.001). In the ATBC Study,
      more deaths from haemorrhagic stroke and fewer from ischaemic heart disease were
      observed among those participants who received alpha-tocopherol compared with
      those who did not. Based on the results of the present study and the ATBC Study,
      we conclude that alpha-tocopherol supplementation may increase the risk of
      clinically important bleedings, particularly when combined with ASA.

PMID- 9920355
TI  - Molecular determinants of arterial calcification.
AB  - Calcification of extracellular matrix (ECM) can be either physiological or
      pathological. Physiological calcification (or mineralization) of ECM is
      restricted to bones, teeth and, to a lesser extent, growth plate cartilages.
      Pathological calcification appears often in the ECM of arteries where it is a
      frequent complication of atherosclerosis. However, calcification of the ECM of
      arteries is not restricted to atherosclerosis. Indeed, human diseases have been
      described that are characterized by calcification of the aortic media in the
      absence of any atherosclerotic lesions. The existence of these rare diseases,
      along with several mouse models recently generated and discussed below, indicates
      that the formation of atherosclerotic lesions and the calcification of the artery
      ECM are controlled by different genetic pathways. This emerging knowledge has
      implications for our understanding of ECM calcification beyond atherosclerosis.

PMID- 9920357
TI  - Histological improvement of oesophagitis after Nissen fundoplication.
AB  - Nissen fundoplication gives lasting relief from symptoms of gastro-oesophageal
      reflux and cures endoscopic oesophagitis effectively. The histological effect on
      the oesophageal mucosa is less clear. We studied the long-term histological
      effect of Nissen fundoplication on refractory gastro-oesophageal disease with
      erosive oesophagitis or Barrett's metaplasia in 33 patients with biopsy both
      before and after antireflux surgery. The median postoperative interval to re
      examination was 80 (range 37-110) months. Symptoms of reflux were greatly
      relieved; 31 (94%) of the 33 patients had none or, at the most, mild symptoms.
      Endoscopic oesophagitis was healed in 26 (79%) of the cases. The histological
      appearance of the oesophageal mucosa had been abnormal in all the patients
      preoperatively, but at follow-up it was normal in 22 cases (67%): in 89% of the
      patients without objectively observed recurrent reflux and in 45% of those with
      recurrence. Both the pre- and postoperative severity of the histological changes
      correlated significantly with the endoscopic grade of oesophagitis (r=0.42,
      P=0.017 and r=0.837, P=0.0001, respectively), but not with the clinical reflux
      score. In conclusion, Nissen fundoplication resulted in histological healing in
      the great majority of patients with oesophagitis.

PMID- 9920358
TI  - Early diagnostic indices for the prevention of Alzheimer's disease.
AB  - Recent progress in our understanding of the pathophysiology of Alzheimer's
      disease (AD) has made it clear that it is a heterogeneous disorder to which both
      genetic and environmental factors contribute. Therefore, it is unlikely that a
      single test for the diagnosis of this disease will be developed. Possible
      candidates for early diagnostic indices have been identified, in addition to
      biological markers, in the fields of neuropsychology, genetics and neuroimaging.
      Many studies have indicated that low scores in tests assessing delayed recall
      predict dementia already years before the actual criteria of dementia are
      fulfilled. Molecular genetic studies have confirmed that the epsilon4 allele of
      the apolipoprotein E (APOE) is also a definite risk factor for AD, and other
      susceptibility genes will probably be identified and confirmed in the near
      future. Evaluation of the hippocampal atrophy by magnetic resonance imaging (MRI)
      scans has been reported to be a sensitive and possible specific indicator of mild
      AD, while possibilities of using functional MRI are currently being explored. A
      combination of low scores in tests assessing delayed recall, small size of the
      hippocampus on MRI and APOE epsilon4 might point to a high risk of developing AD.
      We need extensive follow-up studies to identify which combination of molecular
      genetic factors and memory test scores supplemented with neuroimaging will prove
      to be most efficient in diagnosing AD in its preclinical phase, as this is the
      phase which offers the most promising therapeutic options.

PMID- 9920359
TI  - Molecular genetics of Alzheimer's disease.
AB  - Genetic factors are involved in the aetiology of Alzheimer's disease (AD) in 25
      40% of the cases. In some cases AD clearly segregates as an autosomal dominant
      trait in families. Three genes have been identified which, when mutated, cause
      AD: the Abeta amyloid precursor protein gene (APP), and the presenilin-1 (PSEN1)
      and presenilin-2 (PSEN2) genes. Together, these mutations are responsible for 30
      50% of the cases with autosomal dominant AD, and for about 5% of AD in general.
      In cases where the inheritance pattern is unclear and in sporadic cases the
      epsilon4 allele of the apolipoprotein E gene (APOE) has been identified as a
      major risk factor contributing to the pathogenesis of AD in about 20% of the
      cases. Although mutations in the known genes are a rare cause of AD they are
      useful for the purposes of presymptomatic diagnostics in autosomal dominant AD
      families that segregate these mutations. Also, the identification of these genes
      and mutations has been extremely important to the recent evolution in the
      understanding of the biology of the disease. However, other causative and risk
      genes are involved in AD and need to be identified in order to fully elucidate
      the biology of AD. This will ultimately lead to the development of effective
      therapies for this major disease.

PMID- 9920360
TI  - Animal models in the development of symptomatic and preventive drug therapies for
      Alzheimer's disease.
AB  - Dementia of the Alzheimer type (AD) is clinically characterized by a progressive
      deterioration of intellect, memory, judgment, and abstract thinking. It is
      incurable, and causal therapy is not yet available. For the development of
      therapeutic drugs, valid animal models are needed that mimic the
      pathophysiological change in brain functions and the concomitant behavioural
      deterioration seen in AD patients. This article provides an overview of the
      animal models that are used most often to study the substrates and mechanisms of
      the pathological changes underlying AD and to identify, characterize and develop
      putative neuroprotective, antidegenerative, revalidation-supporting and/or
      cognition-enhancing compounds or treatments. The first generation of agents for
      the symptomatic treatment of the disease has been developed on the basis of
      results obtained with these models. These drugs are presently undergoing clinical
      testing or are already used therapeutically. There is, however, no single animal
      model that can mimic the full range of pathophysiological alterations and key
      symptoms of AD. New, genetically engineered mouse models that mimic at least some
      of the key pathological changes of AD are expected to provide tools that will
      facilitate the development of symptomatic and preventive drug therapies.

PMID- 9920361
TI  - Thyroid hormones modulate serum leptin levels: observations in thyrotoxic and
      hypothyroid women.
AB  - Thyroid hormones and leptin are both involved in the regulation of energy
      metabolism. Serum leptin concentrations were measured in women with
      thyrotoxicosis (n = 21, mean age 45 years) or hypothyroidism (n = 14, mean age 44
      years) before and 3 months after restoration of the euthyroid state. Serum leptin
      concentration tended to increase in both hypothyroid (14.7+/-3.5 vs 17.8+/-3.9
      ng/ml, p = 0.06) and thyrotoxic (11.9+/-1.7 vs 14.4+/-2.0, p = 0.08) women after
      treatment (values given as mean +/- SE in the untreated and the euthyroid state
      respectively). Body mass index (BMI) was lower in thyrotoxic women than in
      hypothyroid women in the untreated state (22.1+/-0.7 vs. 26.2+/-1.9, p < 0.05).
      BMI was not different between both groups after treatment (24.5+/-0.7 vs. 26.3+/
      2.1, p = 0.37), due to an increase of BMI in the thyrotoxic women; BMI did not
      change in the hypothyroid group. After controlling for BMI in a multivariate
      regression analysis, serum leptin concentrations were lower in hypothyroid women
      than in thyrotoxic women (p < 0.05), whereas posttreatment values of leptin did
      not differ (p = 0.44). When leptin concentrations were expressed as standard
      deviation scores (Z-scores) from the mean value of female controls matched for
      BMI and age as reported earlier, Z-scores were lower in the hypothyroid than in
      the thyrotoxic women (-0.63+/-0.21 vs. 0.53+/-0.18, p = 0.001). After treatment,
      Z-scores did not deviate from the expected values (0.05+/-0.28 vs. 0.08+/-0.16, p
      = 0.98). Z-scores differed before and after treatment in both hypothyroid (p =
      0.01) and thyrotoxic (p = 0.02) patients. In conclusion, these data obtained in
      thyrotoxic and hypothyroid women indicate that thyroid states modulates serum
      leptin concentrations independent of BMI, with a small decrease in hypothyroidism
      and a small increase in thyrotoxicosis.

PMID- 9920362
TI  - Value of re-aspirations in benign nodular thyroid disease.
AB  - Fine-needle aspiration cytology (FNAC) is the most useful procedure for the
      evaluation of thyroid nodules. The requirement for repeated aspirations in the
      follow-up of benign nodular thyroid disease, however, is controversial. To
      determine the value of re-aspirations in benign nodular thyroid disease, we
      studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19
      male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151)
      thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46
      were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a
      mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407
      (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and
      papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change
      after multiple aspirations in 213 (98.61%) of the cases. Three patients with
      initial aspirations read as benign had a diagnosis of PC from their second
      biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC
      revealed atypical features in 1 of the 3 patients. These 3 patients likely
      represent a false-negative result of the initial FNAC rather than benign nodular
      disease transformed to a malignant one during the follow-up period. In
      conclusion, a second aspiration of clinically suspicious nodules may correct a
      few initial false-negative results, but routine additional re-aspirations are not
      useful for clinically stable disease.

PMID- 9920363
TI  - Diagnostic value of technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI)
      scintigraphy in detecting thyroid cancer metastases: a critical evaluation.
AB  - Technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy has recently
      been used in clinical application for detecting thyroid cancer metastases, its
      role being considered supplementary to serum thyroglobulin (Tg) measurements and
      radioactive iodine (131I) whole-body scans (WBS). The present retrospective study
      was designed to elucidate the role of 99mTc-MIBI scans in localizing metastatic
      lesions by assessing sensitivity and specificity of the scan results obtained in
      a group of 68 thyroidectomized thyroid cancer patients. Presence or absence of
      thyroid cancer was judged with other diagnostic modes including serum Tg
      measurements, 131I WBS, bone scans, chest x-rays, computed tomography (CT),
      ultrasonography, histopathology, and evolution of disease during follow-up. All
      scans were read on lesion basis for detecting neck, lung, and bone metastases and
      also on region basis, namely head-neck, chest, and abdomen-pelvis-extremities (ab
      p-ex) areas. The sensitivity of detection was 94.4% (17/18) for neck, 78.4%
      (40/51) for lung, and 92.8% (64/69) for skeletal lesions. Positive predictive
      value (PPV) and negative predictive value (NPV) were 96.3% (26/27) and 97.7%
      (43/44) for head-neck; 94.7% (71/75) and 50.0% (12/24) for chest; 100.0% (25/25)
      and 93.1% (54/58) for ab-p-ex regions, respectively. For all scan sites taken
      together, PPV and NPV were 96.1% (122/127) and 86.5% (109/126), respectively. In
      conclusion, the present study reveals that 99mTc-MIBI can be proposed as a first
      line diagnostic agent for the follow-up protocol of thyroid cancer patients,
      although the ability to detect small lung metastases is somewhat limited.

PMID- 9920364
TI  - Correlation of antithyroglobulin and antithyroid-peroxidase antibody profiles
      with clinical and ultrasound characteristics of chronic thyroiditis.
AB  - Patients with chronic thyroiditis were selected for study according to specific
      selection criteria, and comparisons of an enzyme-linked immunosorbent assay
      (ELISA) method to a hemagglutination method were performed. The ELISA assays
      contained antithyroglobulin (TG) antibody and antithyroid-peroxidase (PO)
      antibody, the latter using recombinant human TPO. Four groups were established
      from 437 patients with chronic thyroiditis; 316 with both antibodies (TG + PO
      group), 75 with TG antibody alone (TG group), 10 with PO antibody alone (PO
      group), and 36 with no such antibodies (N group). The hemagglutination assay
      resulted in much different antibody profiles: PO group based on ELISA occurred in
      only 2%, whereas a group with microsome antibody alone based on hemagglutination
      assay occurred in 39%. Subsequently, studies of disease characteristics including
      age, gender, familial predisposition, thyroid function, and morphology of the
      gland were performed among the four groups of patients based on ELISA profiles
      but not on hemagglutination results. The subgroups of TG + PO and TG were derived
      from randomly selected patients (40 out of a much larger number of patients in
      each). The results showed that the PO group had smaller thyroid volume (25+/-16
      mL, mean +/- SD) with normal echogenicity, and 50% prevalence of hypothyroidism.
      The TG group had larger thyroid volume (57+/-42 mL) with frequent association of
      small nodular formation (53%) but less frequent hypothyroidism (23%). In summary,
      compared to the hemagglutination method, the ELISA was noted to have both a
      higher sensitivity and specificity for detection of chronic thyroiditis.
      Correlation of ELISA profiles with ultrasonography of the thyroid gland detected
      subtle differences in subgroups that may account for differences in thyroid gland
      morphology and prevalence of hypothyroidism: the PO group has normal echogenicity
      but high incidence of impaired thyroid function, whereas in the TG group small
      nodules were associated with a lesser incidence of hypothyroidism.

PMID- 9920365
TI  - Normal serum concentrations of sex hormone binding-globulin in patients with
      hyperthyroidism due to subacute thyroiditis.
AB  - Serum concentrations of sex hormone binding-globulin (SHBG) were determined in
      patients with hyperthyroidism (n = 94; 12 men, 82 women) due to either Graves'
      disease (n = 59; 11 men, 48 women), autonomous thyroid adenomas (n = 23; 1 man,
      22 women), or subacute thyroiditis (n = 12; all women). Elevated serum
      concentrations of SHBG were initially seen in 57 of 82 patients (69%) with
      hyperthyroidism due to either Graves's disease or due to autonomous adenoma.
      Elevated serum SHBG concentration was more frequent in patients with serum total
      thyroxine (TT4) concentrations greater than 15.0 microg/dL (32/39 [82%];
      including 3 patients with autonomous adenoma) compared to those with serum TT4
      concentration between 11.0 and 15.0 microg/dL (21/27 [77%]; including 7 patients
      with autonomous adenoma), or patients with an isolated elevation of serum total
      triiodothyronine (TT3) concentration (4/16 [25%]; including 2 patients with
      autonomous adenoma). Serum SHBG concentration normalized when patients became
      euthyroid. Only 1 of 12 patients in the hyperthyroid phase of subacute
      thyroiditis had an elevated serum concentration of SHBG. Serum concentrations of
      thyroid binding globulin (TBG) and transcortin (CBG) were normal in all but 1
      patient. In patients with hyperthyroidism as a result of Graves' disease or
      autonomous adenoma serum SHBG concentrations were elevated with the greatest
      elevation found in patients with the highest serum T4 concentrations. The normal
      concentrations of SHBG in the hyperthyroid phase of subacute thyroiditis most
      likely reflects the shorter duration of exposure to increased thyroid hormone in
      this condition.

PMID- 9920366
TI  - Effectiveness of preoperative radioactive iodine (131I) therapy for locally
      advanced papillary thyroid cancer: a case report.
AB  - We report here the effectiveness of preoperative radioactive iodine-131 (131I)
      therapy for locally advanced thyroid cancer. A 57-year-old woman demonstrated a
      hard neck tumor that markedly invaded the surrounding organs. The cytological
      diagnosis of the tumor using fine-needle aspiration biopsy was papillary
      carcinoma. Because curative resection of the tumor appeared difficult at her
      first visit, 131I therapy was performed prior to surgery and was more useful than
      expected. After 3 131I treatments, the tumor size was greatly reduced, and the
      patient underwent a curative operation. Histopathological diagnosis was well
      differentiated papillary carcinoma, pT4 and pN1b. The postoperative clinical
      course was uneventful. There have been no definitive reports using 131I as
      preoperative treatment for inoperable thyroid cancer. We suggest that 131I
      therapy may also be beneficial as neoadjuvant therapy for locally advanced
      thyroid carcinoma.

PMID- 9920367
TI  - Graves' hyperthyroidism after postpartum thyroiditis.
AB  - Two Caucasian patients are described who had destructive postpartum thyroiditis
      (PPT) before the subsequent onset of Graves' hyperthyroidism (GH). HLA class II
      DQ typing in these two subjects identified putative susceptibility alleles
      previously detected in GH and PPT. Although PPT destructive thyroiditis preceding
      the development of GH is relatively uncommon, the occurrence of both these
      syndromes in the same patient suggests the possibility of an etiological role for
      thyroid antigen release and genetic susceptibility as pathogenic factors in the
      development of Graves' disease.

PMID- 9920368
TI  - Amiodarone-induced thyrotoxicosis associated with thyrotropin receptor antibody.
AB  - Since amiodarone was first marketed in 1992 in Japan, the incidence of amiodarone
      induced thyrotoxicosis (AIT) has been increasing. Among 12 thyrotoxic patients, a
      patient with arrhythmogenic right ventricular dysplasia, who had been taking
      amiodarone for 4 years, developed thyrotoxicosis with subacute onset, accompanied
      by transiently positive thyrotropin (TSH) receptor antibody (TRAb), or
      thyrotropin-binding inhibiting immunoglobulin (TBII). The immunoglobulin G (IgG)
      obtained from the TRAb-positive serum of the patient elicited no thyroid hormone
      releasing activity in cultured human thyroid follicles, whereas all IgGs obtained
      from untreated Graves' disease elicited positive results. These in vitro findings
      and clinical course suggest that TRAb/TBII without thyroid-stimulating activity
      may develop in patients with amiodarone-induced destructive thyroiditis, as
      reported in patients with destructive thyroiditis, such as subacute and silent
      thyroiditis.

PMID- 9920370
TI  - Genetic immunotherapy for medullary thyroid carcinoma: destruction of tumors in
      mice by in vivo delivery of adenoviral vector transducing the murine interleukin
      2 gene.
AB  - A replication defective adenovirus harboring the interleukin-2 gene (AdCMVmIL2)
      was used for treatment of a mouse medullary thyroid carcinoma (mMTC). We
      evaluated the antitumor effect and immunological response in the animal model. In
      small tumors (< or = 30 mm3), intratumor injection of AdCMVmIL2 led to mMTC tumor
      regression in up to 69% of animals. With large tumors (>30 mm3), almost all
      treated tumors showed stabilization in size, but did not completely resolve. All
      mice cured by AdCMVmIL2 treatment failed to develop tumors after reinjection of
      wild-type mMTC cells, indicating that long-term antitumor immunity developed.
      Analysis of cytotoxicity indicates that the antitumor effect in cured mice was
      dependent on cytotoxic T lymphocyte (CTL) activity against the tumor.
      Histological and immunohistological studies of treated tumors revealed massive
      CD4+ and CD8+ cell infiltration in AdCMVmIL2 treated tumors, but not in untreated
      or control virus treated tumors. The data demonstrate the ability of interleukin
      2 (IL-2) to elicit specific antitumor immunity and offer hope for this therapy in
      humans.

PMID- 9920369
TI  - Nitric oxide donors inhibit iodide transport and organification and induce
      morphological changes in cultured bovine thyroid cells.
AB  - Nitric oxide (NO) has been proposed as an intracellular signal in the thyroid.
      The NO effect on function and morphology of bovine thyroid follicles in culture
      was analyzed by using the NO donors sodium nitroprusside (SNP) and S
      nitrosoglutathione (GSNO). Both NO donors induced a concentration-dependent NO
      release measured by the nitrite accumulation in the culture medium. The SNP (10
      to 500 micromol/L) treatment for 24 hours significantly inhibited the uptake,
      organification and transport of iodide in a concentration-dependent manner. When
      SNP (50 micromol/L) was withdrawn from the culture medium after 24 hours'
      incubation, iodide uptake and organification were partially recovered at 24 hours
      and reached the control value at 48 hours, indicating a reversible effect of SNP.
      A possible involvement of cyanide in the SNP inhibitory effect was excluded
      because incubation of follicles with potassium cyanide (KCN) at concentrations
      estimated to be present in the medium (40 and 80 micromol/L) for 24 hours did not
      modify iodide uptake and organification. The GSNO (10 to 500 micromol/L)
      treatment for 24 hours also reduced the iodide uptake, organification and
      transport in a concentration-dependent manner. A significant inhibition of iodide
      organification was induced after incubation with 1000 micromol/L of N2, 2'-O
      dibutyrylguanosine 3':5'-cyclic monophosphate ([Bu]2cGMP). Morphological
      evaluation by light microscopy revealed that the incubation with NPS or GSNO (500
      micromol/L) produced cellular dispersion with loss of follicular cell aggregates
      that was evident at 96 hours exposure. Cell viability was not altered by 10-500
      micromol/L SNP or GSNO (80% to 85%). We concluded that long-term NO exposure
      induces functional and morphological modifications compatible with a loss of
      differentiation in thyroid follicles. These observations further support a role
      of NO in the regulation of the thyroid function.

PMID- 9920371
TI  - Alginate gel culture allows the retention of extracellular matrix and follicular
      structure of rat thyroid tissue but does not lead to the formation of follicles
      by FRTL-5 cells.
AB  - Extracellular matrix (ECM) and basement membrane (BM) components were studied by
      immunohistological methods in native rat thyroid tissue, and in rat thyroid
      tissue and FRTL-5 cells cultured in a three-dimensional alginate bead system. In
      all three situations, the presence of collagen IV, laminin, perlecan, and
      fibronectin was demonstrated. There were marked differences between rat thyroid
      tissue and FRTL-5 cells in culture. Rat thyroid tissue maintained a follicular
      structure, whereas FRTL-5 cells did not form follicles. Rat thyroid cells
      multiplied more slowly than FRTL-5 cells and thyroglobulin (Tg) was visible in
      the follicular lumen, while in FRTL-5 cells Tg was only seen intracellularly. Tg
      iodination was much lower in FRTL-5 cells than in rat cells. In rat thyroid
      cells, positive staining for collagen IV, laminin, and perlecan was seen in thin
      membranes around individual follicles, and for fibronectin around groups of
      follicles. In FRTL-5 cells, these ECM/BM components could be identified, but were
      not organized into equally regular networks around groups of cells. These results
      demonstrate that of the two types of cells examined, primary cultures of rat
      thyroid cells in alginate beads maintain structural and functional similarities
      to native thyroid tissue and would therefore be suitable for future in vitro
      studies of thyroidal ECM/BM and their interrelationship with growth and function
      of this organ. FRTL-5 cells cultured in alginate beads show some functional, but
      not structural similarities to native thyroid tissue and so would be less
      valuable for use in such studies.

PMID- 9920372
TI  - Thyroid hormone inhibits aromatase activity in porcine thecal cells cultured
      alone and in coculture with granulosa cells.
AB  - We cultured porcine thecal and granulosa cells alone or in coculture to define
      whether thyroid hormone affects aromatase activity in porcine ovarian cells.
      Dispersed cells were cultured with 10(-9) M triiodothyronine (T3) for 24 hours.
      Testosterone (final concentration 10(-7) M) was added as aromatase substrate for
      granulosa cells (Gc) cultured alone. Thecal (Th) androgens serve as a substrate
      for estradiol secretion by Th cells cultured alone and in coculture with Gc. At
      the end of the preincubation time, the culture media was removed and replaced
      with fresh media containing 100 ng follicle stimulating hormone (FSH) or 10(-3) M
      8-bromo-cyclic adenosine monophosphate (8-Br-cAMP). After overnight incubation,
      the culture media was analyzed for estradiol production by radioimmunoassay
      (RIA). T3 inhibited basal, FSH-stimulated, and 8brcAMP-stimulated estradiol
      production in all culture conditions. T3 inhibited cAMP analogue 8-Br-cAMP and
      FSH-induced aromatase activity to a similar extent, thus suggesting that the
      inhibitory effect of T3 is downstream of cAMP formation. In the second part of
      the experiment a rabbit polyclonal antibody against human placental cytochrome P
      450arom was used to confirm the effect of T3 on aromatase protein in Th and Gc.
      Pretreatment of Th and Gc with T3 markedly decreased immunostaining for aromatase
      in both types of cells, suggesting a direct effect of T3 on this enzyme.

PMID- 9920373
TI  - Cardiac risks of hyperthyroidism in the elderly.
AB  - The importance of cardiovascular system involvement in hyperthyroidism has been
      recognized for many years. In the elderly patient, often with mild but prolonged
      elevation of plasma thyroid hormones, symptoms and signs of heart failure and
      complicating atrial fibrillation (AF) may dominate the clinical picture and mask
      the more classic endocrine manifestations of the disease. Impaired
      cardiopulmonary function and exercise capacity, significantly more marked in
      older patients, is observed in hyperthyroidism. Thyrotoxicosis can aggravate pre
      existing heart disease and can also lead to AF, congestive heart failure, or
      worsening of angina pectoris. Regarding the high incidence of AF in older
      patients with hyperthyroidism, it is also important to detect subclinical
      hyperthyroidism in older patients with AF, thus warranting the measurement of the
      serum thyrotropin (TSH) concentration for early recognition and treatment. Most
      cardiac abnormalities return to normal once a euthyroid state has been achieved,
      although AF may persist in a minority. Optimal treatment requires rapid and
      definitive antithyroid therapy. Furthermore, anticoagulation is recommended for
      thyrotoxic patients with AF older than 50 years, those who have histories of
      previous emboli, hypertension, or with echocardiographic evidence of left atrial
      enlargement and/or myxomatous valves.

PMID- 9920374
TI  - Hyperthyroidism in early infancy: pathogenesis, clinical features and diagnosis
      with a focus on neonatal hyperthyroidism.
AB  - Neonatal hyperthyroidism has mostly been described in the context of maternal
      Graves' disease. It has been estimated that about 0.2% of pregnant women have
      Graves' disease; however only 1% of the children born to these women are
      described as having hyperthyroidism. In most of the cases, the disease is due to
      maternal antibodies transferred from the mother into the fetal compartment, which
      stimulate the fetal thyroid by binding to the thyrotropin (TSH) receptor. In this
      form of neonatal hyperthyroidism, thyrotoxicosis disappears with the clearance of
      the maternal antibodies and usually signs disappear during the first 4 months of
      life. Rare forms of persistent, nonimmune neonatal hyperthyroidism are explained
      by molecular abnormalities of the TSH receptor. Prematurity is frequent, as well
      as hypotrophia. Tachycardia, goiter, hyperexcitability, poor weight gain,
      hepatomegaly and/or splenomegaly, stare and/or eyelid retraction are among the
      most frequent neonatal thyrotoxicosis clinical signs. Diagnosis is based on the
      determination of the blood level of thyroxine (T4), triiodothyronine (T3), and
      TSH. Even if these levels are normal in the cord blood, tests should be repeated
      3 to 10 days later to detect possible delayed appearance of the disorder. These
      parameters should be interpreted according to the age of the neonate. To confirm
      the immune nature of this hyperthyroidism, thyroid-stimulating immunoglobulins
      (TSI) should be determined. The TSI determination is crucial in identifying
      nonimmune causes of neonatal hyperthyroidism: in this neonatal hyperthyroidism,
      TSI are not detected, either by radioreceptor assay and/or by functional assay,
      and molecular studies are needed to identify the mutation. Mutation of the TSH
      receptor leading to its constitutive activation and to neonatal hyperthyroidism
      have been described. Germline mutations are found in hereditary hyperthyroidism;
      de novo germline mutations can cause sporadic congenital hyperthyroidism.

PMID- 9920375
TI  - Epidemiology of thyroid diseases in iodine sufficiency.
AB  - Epidemiology of thyroid diseases in iodine-sufficient areas (ISA) deals with
      sporadic goiter, thyroid autoimmune diseases, and thyroid cancer. A comparison
      between the different studies performed is difficult because methods have changed
      over time and selection criteria and definitions such as prevalence or incidence
      were not used consistently by some authors. Sporadic goiter: in ISA, autoimmune
      processes play a major role in the development of sporadic goiter. In adults,
      sporadic diffuse goiter is most frequent in young women (16%), perhaps due to
      additional relative iodine deficiency especially in pregnancy, and declines with
      age (<10%). Sporadic nodular goiter increases from 5% in young women to 9% in
      older women. Autoimmune thyroid disease (AITD): thyroid autoantibodies (TAb) and
      histopathological lymphocytic infiltration of the thyroid is much more common in
      ISA (4.6% in women; 1.1% in men) than in iodine-deficient areas (IDA). The
      prevalence and incidence of hypothyroidism and hyperthyroidism varies, depending
      on whether overt and subclinical forms are included and whether newly or
      previously diagnosed dysfunction is considered. In an overview of the literature,
      the prevalence is 2 in 1000 for overt and 6 in 1000 for subclinical
      hyperthyroidism in ISA. The values for hypothyroidism are 5 in 1000 and 15 in
      1000, respectively. Change from IDA to ISA: in former IDA, the percentage of
      hyperthyroidism increases up to 4 years after salt iodination. Whereas this
      effect is transient for Plummer's disease, a change from IDA to ISA seems to lead
      to a permanent increase in overt and subclinical Graves' disease. Thyroid cancer:
      most studies demonstrate that the histopathological types of thyroid cancer are
      different in IDA and ISA. There is a tendency toward an increase in
      differentiated and decrease of anaplastic cancer. The ratio of papillary to
      follicular thyroid cancer ranges from 6.5:1 to 3.4:1 in areas with high iodine
      intake, decreases 3.7:1 to 1.6:1 in areas with moderate iodine intake, and ranges
      from 1.7:1 to 0.19:1 in IDA.

PMID- 9920376
TI  - Screening for congenital hypothyroidism used as an indicator of the degree of
      iodine deficiency and of its control.
AB  - Neonatal thyroid screening using serum thyrotropin (TSH) as the primary screening
      test detects not only permanent sporadic congenital hypothyroidism, whose
      incidence is about 1 per 4000 births, but also compensated or transient primary
      hypothyroidism, whose incidence can be as high as 1 in 10 neonates and whose main
      cause is iodine deficiency. Elevated serum TSH in the neonate indicates
      insufficient supply of thyroid hormones to the developing brain, and therefore,
      constitutes the only indicator that allows prediction of possible impairment of
      mental development at a population level, which is the main consequence of iodine
      deficiency. Therefore, the World Health Organization (WHO), United Nations
      International Children's Emergency Fund (UNICEF), and the International Council
      for Control of Iodine Deficiency Disorders (ICCIDD) included neonatal TSH as one
      of the indicators for assessing iodine deficiency disorders (IDD) and their
      control. In the absence of iodine deficiency, the frequency of neonatal TSH above
      5 mU/L whole blood (or 10 mU/L serum) is less than 3%. A frequency of 3%-19.9%
      indicates mild IDD. Frequencies of 20%-39.9% and above 40% indicate moderate and
      severe IDD, respectively. Neonates exhibit elevated serum TSH more frequently
      than adults for a similar degree of iodine deficiency. Consequently, they appear
      hypersensitive to the effects of iodine deficiency. This characteristic is
      explained by a particularly low iodine content of the thyroid of neonates and,
      consequently, by an accelerated turnover rate of their intrathyroidal iodine
      reserves. This turnover rate is 1% in adults. It is 17% in the neonate in
      conditions of iodine repletion, but is as high as 62% and 125% in conditions of
      moderate and severe iodine deficiency, respectively. Such an accelerated turnover
      rate requires thyroid hyperstimulation by TSH that is morphologically evidenced
      even in moderately iodine deficient neonates. Neonatal screening using primary
      TSH is implemented in most countries with mild IDD where it detects the cases of
      sporadic, permanent congenital hypothyroidism and where it is also used as a
      monitoring tool for IDD evaluation and control. However, the implementation of
      such programs in countries affected by moderate or severe IDD is still
      insufficient because of lack of resources of the countries. This should be
      considered in the framework of the external support often provided to these
      countries for the implementation of programs of universal salt iodization.
      Monitoring of these programs in order to achieve the goal of sustainable
      elimination of IDD now constitutes an absolute priority.

PMID- 9920377
TI  - Radioiodine therapy and Graves' ophthalmopathy.

PMID- 9920378
TI  - Thyroid One. Thyroid Cancer Pathogenesis, Diagnosis including PET, and Treatment.
      International Symposium. October 7-10, 1998, Linz, Austria. Abstracts.

PMID- 9920380
TI  - Solution structure of a fragment of the dimerization domain of DP-1 determined by
      1H-nuclear magnetic resonance and distance geometry.
AB  - The structure of a synthesized peptide with the sequence of
      NHILPNESAYDQKNIRRRVYDALNVLMAMNIISK that corresponds to residues 151-184 of
      transcription factor DP-1 (Girling et al., Nature 362 (1993) 83-87) was
      determined by 1H-nuclear magnetic resonance in water and 40% d3
      trifluoroethanol/water, respectively. Nuclear Overhauser effect cross peaks,
      alphaH chemical shifts and J-coupling constants of alphaH-NH show that the
      peptide consists a helix from Ser-8 to Ser-33 in solution. Fifty structures were
      constructed with 288 upper distance limits and 21 angle constraints by DIANA
      (Guntert et al., J. Mol. Biol. 217 (1991) 517-530). Although the N-terminal of
      the peptide exhibits a random conformation, the 20 best structures show a root
      mean square deviation of 0.89+/-0.36 A for backbone atoms and 1.80+/-0.34 A for
      heavy atoms from residue Ser-8 to Ser-33. This result supports the proposal that
      DP-1 and E2F-1 may dimerize with a coiled-coil type interaction.

PMID- 9920379
TI  - Pyroglutamyl peptidase: an overview of the three known enzymatic forms.
AB  - Pyroglutamyl peptidase can be classified as an omega peptidase which
      hydrolytically removes the amino terminal pyroglutamate (pGlu) residue from
      specific pyroglutamyl substrates. To date, three distinct forms of this enzyme
      have been identified in mammalian tissues. Type I is typically a cytosolic,
      cysteine peptidase displaying a broad pyroglutamyl substrate specificity and low
      molecular mass. Type II has been shown to be a membrane anchored metalloenzyme of
      high molecular mass with a narrow substrate specificity restricted to the
      hypothalamic releasing factor, thyrotropin-releasing hormone (TRH, pGlu-His-Pro
      NH2). A third pyroglutamyl peptidase activity has also been observed in mammalian
      serum which displays biochemical characteristics remarkably similar to those of
      tissue Type II, namely a high molecular mass, sensitivity to metal chelating
      agents, and a narrow substrate specificity also restricted to TRH. This serum
      activity has subsequently been designated 'thyroliberinase'. This review surveys
      the biochemical, enzymatic, and structural properties of this interesting and
      unique class of peptidases. It also addresses the putative physiological roles
      which have been ascribed to these enzymes. Pyroglutamyl peptidase activities
      isolated and characterized from bacterial sources are also reviewed and compared
      with their mammalian counterparts.

PMID- 9920381
TI  - D-arabinose dehydrogenase and its gene from Saccharomyces cerevisiae.
AB  - D-Arabinose dehydrogenase was purified 843-fold from the cytosolic fraction of
      Saccharomyces cerevisiae with a recovery of 9%. The purified enzyme gave two
      bands with a molecular mass of 40 and 39 kDa on SDS-PAGE. The native enzyme had a
      molecular mass of 74 kDa as estimated by Sephacryl S-200 chromatography.
      Therefore, this enzyme was considered to be a heterodimer. The purified enzyme
      exhibited maximum activity at pH 10.0 and around 30 degrees C. The enzyme
      catalysed the oxidation of D-arabinose, L-xylose, L-fucose and L-galactose in the
      presence of NADP+. The apparent Km values at pH 10.0 with 50 microM NADP+ for D
      arabinose, L-xylose, L-fucose, and L-galactose were 161, 24, 98 and 180 mM,
      respectively. The pH profile of Vmax and kcat/Km showed one ionisable groups
      around pH 8.3. D-Erythroascorbic acid was formed in vitro from D-arabinose by D
      arabinose dehydrogenase and D-arabinono-1,4-lactone oxidase. The N-terminal amino
      acid sequence of the heavy subunit was Ser-Thr-Glu-Asn-Ile-Val-Glu-Asn-Met-Leu
      His-Pro-Lys-Thr-. The N-terminus of the light subunit was blocked. The obtained
      peptide sequence was identical to the translational product of an unknown open
      reading frame, YBR149W, in chromosome II of S. cerevisiae. When compared with the
      translational product of this open reading frame, the peptide sequence was
      identical to the amino acid sequences of residues 7 to 20. The first six amino
      acids of this open reading frame were lost in protein sequence, which may be
      modified post-translationally. The heavy subunit was composed of 344 amino acid
      residues and its deduced amino acid sequence contained the motifs I, II, and III
      of aldo-keto reductase and also leucine zipper motif. This enzyme is the first
      heterodimeric protein of aldo-keto reductase family. In the deletion mutant of
      this gene, D-arabinose dehydrogenase activity and D-erythroascorbic acid were not
      detected.

PMID- 9920382
TI  - Two-dimensional crystals of reconstituted beta-subunits of the chaperonin TF55
      from Sulfolobus shibatae.
AB  - We have obtained 2-dimensional crystals of the beta-subunits of the chaperonin
      TF55 from Sulfolobus shibatae reconstituted into oligomers in the absence of
      alpha-subunits. The subunits form rings with 9-fold rotational symmetry which
      arrange themselves in a trigonal lattice. From electron micrographs of negatively
      stained specimens we have calculated a projection map in plane group p312 showing
      the rings in top-view.

PMID- 9920383
TI  - Protein-protein interactions in the assembly of Shigella flexneri invasion
      plasmid antigens IpaB and IpaC into protein complexes.
AB  - Shigella flexneri is a facultative intracellular bacterial pathogen that invades
      human colonic epithelial cells by a process called pathogen-induced phagocytosis.
      Pathogen entry requires three virulence plasmid-encoded proteins called invasion
      plasmid antigens (Ipa) B, C and D which are secreted upon bacterial contact with
      a host cell. Following their secretion, IpaB and IpaC are found within a complex
      of proteins that may also contain IpaA and IpaD. Previous work has shown that
      exogenously added recombinant IpaC is sufficient for promoting the uptake of S.
      flexneri in gentamicin-protection assays. It is shown here that purified
      recombinant Ipa proteins can also be used to investigate the formation of Ipa
      protein complexes in vitro. The protein-protein contacts involved in the
      formation of Ipa complexes appear to include previously undescribed IpaC-IpaC
      interactions in addition to a strong association between IpaB and IpaC. IpaD does
      not appear to interact with either IpaB or IpaC in vitro although it is possible
      that recombinant IpaD forms homodimers that are stabilized by disulfide bridges
      involving this protein's single cysteine residue. This investigation represents
      the first characterization of the biochemistry of Ipa complex assembly.

PMID- 9920384
TI  - Organization of microfibrils in keratin fibers studied by X-ray scattering
      modelling using the paracrystal concept.
AB  - Low-angle X-ray scattering patterns of hard alpha-keratin fibers have been
      studied for more than 50 years but a completely convincing modelling has never
      been presented. The models which have been proposed so far are specific to the
      sample and cannot be adapted to others, mainly because they do not use a
      parametric analytical expression of the distribution function describing the
      relative positions of the microfibrils. Our new approach is based on a
      paracrystal distribution function. In addition, a huge background originating
      from a non-ordered matrix is taken into account. Various hard alpha-keratins from
      different origins have been studied using our approach. From the rather good
      modellings obtained, it appears that the diameter of the microfibril is not
      origin dependent (7.4 nm) whereas the distances between microfibrils and their
      electron density profiles are. Hair microfibrils can be reasonably approximated
      by a solid cylinder but a core and an outer ring are necessary for porcupine. Our
      method is of course not limited to keratin microfibrils; it can be used for
      modelling equatorial X-ray scattering profiles of all types of hexagonal
      fibrillar assemblies, which are in fact widely found in biological tissues.

PMID- 9920385
TI  - Hydrophilic Thr can replace the hydrophobic and absolutely conservative A3Val in
      insulin.
AB  - A mutant insulin, [A3Thr]human insulin, was obtained by means of site-directed
      mutagenesis. The [A3Thr]human insulin retains 50% receptor-binding potency and
      nearly total in vivo biological activity compared with native insulin, and can be
      crystallized using the same condition of native insulin. The results demonstrate
      that the absolutely conservative and hydrophobic valine at A3 can be substituted
      by hydrophilic threonine.

PMID- 9920386
TI  - Identification and mapping of linear antigenic determinants of chicken riboflavin
      carrier protein.
AB  - All of the possible 212 overlapping octapeptides covering the amino acid sequence
      of chicken egg white riboflavin carrier protein (RCP) was synthesized on
      polyethylene rods. To identify the peptides constituting the sequential antigenic
      epitopes on chicken RCP, a PEPSCAN ELISA was employed where antibodies raised
      against SDS-treated, reduced and carboxymethylated RCP (RCM-RCP) in mice, rats (n
      = 4), rabbits and monkeys (n = 3) were used. By this approach, we could identify
      five sequences on chicken RCP commonly recognized by all the antisera from these
      species which were spanning the residues 10-17, 42-49, 134-141, 172-179 and 200
      207. Analysis of the data for each individual antiserum indicated inter- and
      intra-species variations with N- and C-terminal shifts in peak reactivity. The
      present study offers clues for development of potential immunocontraceptive
      vaccines.

PMID- 9920387
TI  - 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a
      comparison of the enzyme from different species.
AB  - The mechanism of action of 6-phosphogluconate dehydrogenase with the alternative
      substrate 2-deoxy 6-phosphogluconate was investigated using enzymes from sheep
      liver, human erythrocytes and Trypanosoma brucei. The three enzymes oxidize 2
      deoxy 6-phosphogluconate, but only the sheep liver enzyme releases the
      intermediate 2-deoxy,3-keto 6-phosphogluconate. Kinetic comparison showed that an
      increase in the rate of NADP+ reduction at high pH is due to increased release of
      the intermediate, rather than an increase in the overall reaction rate. 2-Deoxy,3
      keto 6-phosphogluconate is decarboxylated by the erythrocyte and trypanosome
      enzymes but not the liver one in the absence of either NADPH or 6
      phosphogluconate, which act as activators. The pH dependence of decarboxylation
      and the degree of activation suggest that 6-phosphogluconate is the activator
      which operates under normal assay conditions, while NADPH acts mainly by
      increasing the binding of the intermediate. The data suggest that the activity of
      6PGDH is subjected to a two-way regulation: NADPH, which regulates the pentose
      phosphate pathway, inhibits the enzyme, while 6-phosphogluconate, levels of which
      rise when NADPH inhibition is removed, acts as an activator ensuring that 6
      phosphogluconate is rapidly removed.

PMID- 9920388
TI  - Interaction of adenosine nucleotide analogs with Saccharomyces cerevisiae
      phosphoenolpyruvate carboxykinase.
AB  - The substrate characteristics and interactions of different adenosine nucleotide
      analogs with Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase
      were investigated by steady-state kinetic analysis and calculations of
      interaction energies. Comparison of Vmax/Km values showed that analogs
      substituted at C8 in the adenine ring (8-Br-ATP, 8-N3-ATP, 8-N3-ADP) gave almost
      the same kinetic values as ATP and ADP, whereas those substituted in the ribose
      hydroxyls (3'(2')-O-(N-methylanthraniloyl)-ATP (MANT-ATP), 3'(2')-O-(N
      methylanthraniloyl)-ADP (MANT-ADP), 2'(3')-O-(2,4,6-trinitrophenyl)-ADP (TNP
      ADP), 2'(3')-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP)) showed 1-8% the value for
      the corresponding physiological substrate. A comparison between the experimental
      results and molecular mechanics calculations was performed, employing a model for
      the S. cerevisiae PEP carboxykinase-ATP-Mn2+ complex. The calculated interaction
      energies of S. cerevisiae PEP carboxykinase with ATP, MANT-ATP, TNP-ATP, 8-Br
      ATP, and 8-N3-ATP were linearly related (correlation coefficient 0.92) with 
      ln(Vmax/Km). This good correlation supports the proposal that the interaction of
      the substituent with the enzyme affects the interaction of the common region of
      ATP with the active site, thus leading to effects in Vmax.

PMID- 9920389
TI  - Binding sites for the (Hg-Se) complex on selenoprotein P.
AB  - The mechanism underlying the interaction between mercury (Hg), selenium (Se) and
      selenoprotein P (Sel P) in the bloodstream has been explained by the formation of
      the [(Hg-Se)n]m-Sel P complex. In the present study, the binding sites for the
      (Hg-Se)n complex on Sel P were studied by competitive assay of the binding of the
      (Hg-Se)n complex to Sel P with polymeric and monomeric amino acids with
      simultaneous detection of the Hg, Se of selenite origin and Se of Sel P origin by
      the high performance liquid chromatography-inductively coupled argon plasma-mass
      spectrometry method. The specific binding of the (Hg-Se) complex but not Hg2+ or
      selenide to Sel P was explained by the unique binding sites consisting of the
      cationic and anionic ends such as imidazolyl and selenol groups on Sel P,
      respectively. The number, n, in the (Hg-Se)n complex was estimated to be approx.
      100, while the number, m, in the [(Hg-Se)n]m-Sel P complex was estimated to be
      35. The formation of the unit complex (Hg-Se)100, followed by its binding to Sel
      P at up to the 35 binding sites on Sel P was suggested.

PMID- 9920390
TI  - Statistical analysis of predicted transmembrane alpha-helices.
AB  - Statistical analyses were undertaken for putative transmembrane alpha-helices
      obtained from a database representing the subset of membrane proteins available
      in Swiss-Prot. The average length of a transmembrane alpha-helix was found to be
      22-21 amino acids with a large variation around the mean. The transfer free
      energy from water to oil of a transmembrane alpha-helix in bitopic proteins, -48
      kcal/mol, is higher than that in polytopic proteins, -39 kcal/mol, and is nearly
      identical to that obtained by assuming a random distribution of solely
      hydrophobic amino acids in the alpha-helix. The amino acid composition of
      hydrophobic residues is similar in bitopic and polytopic proteins. In contrast,
      the more polar the amino acids are, the less likely they are to be found in
      bitopic proteins compared to polytopic ones. This most likely reflects the
      ability of alpha-helical bundles to shield the polarity of residues from the
      hydrophobic bilayer. One half of all amino acids were distributed nonrandomly in
      both bitopic and polytopic proteins. A preference was found for tyrosine and
      tryptophan residues to be at the ends of transmembrane alpha-helices. Correlated
      distribution analysis of amino acid pairs indicated that most amino acids are
      independently distributed in each helix. Exceptions are cysteine, tyrosine, and
      tryptophan which appear to cluster closely to one another and glycines which are
      preferentially found on the same side of alpha-helices.

PMID- 9920391
TI  - Direct evidence of the generation in human stomach of an antimicrobial peptide
      domain (lactoferricin) from ingested lactoferrin.
AB  - The ability to define specific alterations in the structure and function of
      proteins as they are introduced and processed in vivo remains an important goal.
      We have evaluated the generation, in vivo, of an antimicrobial peptide
      (lactoferricin) derived from ingested bovine lactoferrin by surface-enhanced
      laser desorption/ionization (SELDI). SELDI was used in the affinity mass
      spectrometry operational mode to detect and quantify lactoferricin directly from
      unfractionated gastric contents using a chemically defined ligand with a terminal
      n-butyl group as the lactoferricin affinity capture device. By this method, we
      were able to detect and quantify lactoferricin directly upon examination of
      unfractionated gastric contents recovered from an adult subject 10 min after
      ingestion of bovine lactoferrin (200 ml of 10 mg/ml (1.2 x 10(-4) mol/l)
      solution). Lactoferricin produced in vivo was directly captured by a surface
      enhanced affinity capture (SEAC) device composed of molecules with a terminal n
      butyl group and analyzed by laser desorption/ionization time-of-flight mass
      spectrometry. The recovery of standard lactoferricin or lactoferrin added to an
      aliquot of the gastric contents was determined to be nearly 100%, confirming the
      efficiency of this method. The amount of lactoferricin detected in the gastric
      contents was 16.9+/-2.7 microg/ml (5.4+/-0.8 x 10(-6) mol/l). However, a large
      proportion of ingested lactoferrin was found to be incompletely hydrolyzed.
      Lactoferrin fragments containing the lactoferricin region were analyzed by in
      situ pepsin hydrolysis after being captured on the SEAC device. Partially
      degraded lactoferrin fragments containing the lactoferricin region, including
      fragments corresponding to positions 17-43, 17-44, 12-44, 9-58 and 16-79 of the
      bovine lactoferrin sequence, were found to be present at concentrations as high
      as 5.7+/-0.7 x 10(-5) mol/l. These results suggest that significant amounts of
      bovine lactoferricin would be produced in the human stomach following ingestion
      of food, such as infant formula, supplemented with bovine lactoferrin. We propose
      that physiologically functional quantities of human lactoferricin could be
      generated in the stomach of breast-fed infants, and possibly, in the case of
      adults, from lactoferrin secreted into saliva.

PMID- 9920392
TI  - X-ray studies on two forms of bovine beta-trypsin crystals in neat cyclohexane.
AB  - Two orthorhombic forms (Vm values are 2.3 and 3.0 A3/Da) of bovine beta-trypsin
      crystals in neat cyclohexane were determined to 1.93 A resolution, by X-ray
      diffraction. Both structures in organic solvent are similar to those in aqueous
      solution. In the high packing density form, one cyclohexane molecule is found in
      a hydrophobic site near the active center. One sulfate locates at the active site
      with hydrogen or salt bond to the Ser-His catalytic diad, and five more sulfates
      bind on the molecular surface. The conformation of the side chains near the
      sulfates changed greatly. In the low packing density form, one cyclohexane and
      three sulfates are found. In both structures, one benzamidine molecule locates at
      the hydrophobic pocket of the active center. Most water molecules on the enzyme
      surface are retained except some with high temperature factors.

PMID- 9920394
TI  - Determination of zero-field splitting and evidence for the presence of charge
      transfer transitions in the Soret region of high-spin ferric hemoproteins
      obtained from an analysis of low-temperature magnetic circular dichroism.
AB  - Theoretical expressions for magnetic circular dichroism (MCD) of the porphyrin pi
      ->pi*, spin-allowed charge transfer (CT) and spin-forbidden d-d or CT transitions
      in high-spin ferric heme are derived. The transitions can be discriminated by
      their MCD to absorption ratio and/or temperature dependence of MCD intensity. An
      analysis of the Soret MCD of fluoride complexes of myoglobin (Mb), hemoglobin
      (Hb) and horseradish peroxidase (HRP), recorded at temperatures from 290 down to
      2 K, is given. It is shown that the Soret MCD of HRPF can be well described by
      overlapping of the pi-->pi* transition with one spin-forbidden CT transition of
      an 6A1-->4E type. In the case of MbF and HbF it is necessary to assume the
      presence in the Soret region of the second spin-forbidden CT transition, most
      probably of an 6A1-->4A1 type. The parameters of transitions have been extracted
      from a non-linear least-squares fitting procedure. The best fit values of
      parameter D of the zero-field splitting of the ground manifold for HbF (6.1 cm(
      1)) and MbF (6.4 cm(-1)) agree well with those obtained by other methods. The D
      value for HRPF (8.3 cm(-1)) is obtained for the first time.

PMID- 9920393
TI  - Primary structure of two major cuticular proteins from the migratory locust,
      Locusta migratoria, and their identification in polyacrylamide gels by mass
      spectrometry.
AB  - The complete amino acid sequence has been determined for two proteins, LmACP21
      and LmACP22, which are prominent components of adult pharate cuticle from the
      migratory locust, Locusta migratoria. The proteins have relative molecular masses
      (Mr) of 16853 and 16879, respectively. They were purified by standard
      chromatographic methods, and the primary structures were determined by combined
      use of mass spectrometry and automatic Edman degradation. The proteins are
      characterized by the presence of a conserved, hydrophilic central sequence with
      pronounced similarity to sequences reported for cuticular proteins from other
      insect species, while the N- and C-terminal regions are dominated by the amino
      acids alanine, valine and proline. The electrophoretic identity of the two
      proteins was confirmed by matrix assisted laser desorption ionization mass
      spectrometry (MALDIMS) of the electroeluted LmACP21/22 proteins from a two
      dimensional electrophoresis gel. The mass spectrometric analysis established the
      presence of additional proteins in close proximity to the LmACP21/22 gel spot.
      One of these proteins, Mr 16134, was identified as LmACP18, and enzymatic
      digestion indicated that it is structurally closely related to LmACP21 and
      LmACP22.

PMID- 9920395
TI  - Identification by site-directed mutagenesis of amino acid residues in ribosomal
      protein L2 that are essential for binding to 23S ribosomal RNA.
AB  - The ribosomal protein L2 (BstL2) from Bacillus stearothermophilus is a primary
      23S rRNA binding protein. We made use of site-directed mutagenesis to identify
      essential basic and aromatic amino acid residues for 23S rRNA binding. Four
      mutants, R68Q, K70Q, R86Q, and R155Q, in which Arg-68, Lys-70, Arg-86, and Arg
      155, respectively, are replaced by the Gln residue. showed reduced binding
      affinities as compared with that of the wild type BstL2 (a binding constant
      K=8.93 microM(-1)): K values of these mutants range between 0.24 and 1.86 microM(
      1). As for aromatic amino acids, replacements of Phe-66, Tyr-95 or Tyr-102 by
      alanine significantly abolished the binding affinities. CD analysis of the mutant
      proteins indicated that the mutations of four basic residues (Arg-68, Lys-70, Arg
      86 and Arg-155) did not affect protein structure, whereas those of aromatic
      residues (Phe-66, Tyr-95, and Tyr-102) appeared to cause slight structural
      perturbations. These results, together with sequence comparison of L2 family
      proteins, suggest that Arg-86 and Arg-155 in BstL2 may act as positively charged
      recognition groups for negatively charged phosphate backbone of the 23S rRNA, and
      that Phe-66, Tyr-95, and Tyr-102 may be candidate residues which stabilize the
      BstL2-23S rRNA interaction through intramolecular interactions.

PMID- 9920396
TI  - Sidechain and backbone requirements for anti-invasive activity of laminin peptide
      11.
AB  - The structure of laminin peptide 11 (CDPGYIGSR-NH2) contains valuable information
      for the design of mimetic compounds with anti-invasive and anti-metastatic
      properties. An alanine scan replacement experiment identified Tyr5, Ile6 and Arg9
      residues as contributing significantly to anti-invasive activity. Circular
      dichroism spectra and NMR alphaH chemical shift values both supported the
      existence of populations of nonrandom coil solution structures for the analogs
      tested. A D-Ala4 for Gly4 substituted analog completely lost activity, while an L
      Ala4 for Gly4 substituted analog retained half the activity of the parent
      peptide. These results complement our previous findings with D/L alanine
      substitutions at the Gly7 position, and together they suggest an 'S'-shaped
      backbone as likely for the active peptide conformation. NMR-constrained molecular
      modeling supported a direct involvement of the Tyr5 and Ile6 sidechains in
      conferring bioactivity, and indicated that the Tyr5 sidechain was buried in the
      Ala2 for Asp2 substitution. Based on the fact that the peptide 11 sequence
      derives from the disulfide bonded c-loop of an LE-repeat, we synthesized the
      cyclic CDPGYIGSRC-NH2 peptide. This analog exhibited good anti-invasive and anti
      metastatic activity. NMR modeling experiments suggested that the trans-proline
      cyclic peptide, would favor an 'S'-shaped backbone conformation. Full retro
      inverso analogs of peptide 11 were shown to have anti-invasive activity inferior
      to that of peptide 11. This weak bioactivity was probed using NMR-constrained
      molecular dynamics, and revealed potential conformations which limited the
      ability of the required sidechains to mimic the positions of those in the native
      peptide conformations.

PMID- 9920397
TI  - Purification and analysis of RTI40, a type I alveolar epithelial cell apical
      membrane protein.
AB  - RTI40 is a 40-42 kDa protein that, within the lung, is specific to the apical
      plasma membrane of the rat alveolar type I cell. Type I cells cover greater than
      95% of the internal surface area of the lung. In this report, we describe some of
      the physical properties of RTI40, and its purification to homogeneity. By liquid
      phase isoelectric focusing, the pI of the protein is 3.0+/-0.5. In two
      dimensional immunoblots, there is a 1.0 pH unit charge train, suggesting post
      translational modification of the protein. We have purified the protein to
      homogeneity by the following method. A membrane preparation from perfused rat
      lungs was extracted with detergent and applied to an ion-exchange column.
      Immunoreactive fractions from the column were pooled, dialyzed and further
      fractionated by reverse phase high performance liquid chromatography (HPLC).
      Essentially all the antigenicity was recovered in one protein peak that was
      homogeneous both by spectral analysis and silver-stained polyacrylamide gels.
      Because the purified protein was N terminus blocked, we cleaved the protein with
      CNBr and fractionated peptide fragments by reverse phase HPLC. Fractions were
      pooled and concentrated. Direct amino acid sequencing of the major peptide
      fragment yielded a 15 amino acid peptide homologous to a mouse osteoblast
      protein, OTS-8. Analysis of purified RTI40 shows that the protein contains
      glycan, some of which is sialic acid. Characterization of RTI40 should facilitate
      future studies of the functional properties of RTI40.

PMID- 9920398
TI  - The fibrinogen RIBS-I epitope (gamma373-385) appears proximate to the gamma408
      411 adhesive domain but is not involved in interaction between receptor-bound or
      surface-adsorbed fibrinogen and platelet GPIIbIIIa.
AB  - The carboxyl terminus of the fibrinogen (Fg) gamma chain (gamma400-411) is
      necessary and sufficient to support platelet aggregation and adhesion. However, a
      monoclonal antibody (mAb) to the Fg RIBS-I epitope (gamma373-385), the anti-Fg
      RIBS-I, which binds only to platelet-bound or surface-adsorbed Fg but not soluble
      Fg, inhibits platelet aggregation. In this study, we showed that this same
      antibody also inhibits the adhesion of platelets to Fg-coated polystyrene beads.
      We then investigated the mechanisms by which the anti-Fg-RIBS-I antibody inhibits
      platelet aggregation and adhesion. The Fg RIBS-I epitope does not interact with
      platelet GPIIbIIIa, since recombinant Fg missing the last four amino acids, the
      Ala-Gly-Asp-Val, on the carboxyl terminus of its gamma chains supports neither
      platelet aggregation nor adhesion to surfaces, nor GPIIbIIIa binding, while it
      binds anti-Fg-RIBS-I normally. Purified, soluble GPIIbIIIa (265 kDa) inhibits the
      binding of both the anti-Fg-RIBS-I and 4A5 (a mAb specific to gamma408-411 of
      Fg), however, peptide G13 (1.5 kDa), corresponding to the Fg gamma chain binding
      domain on GPIIba (GPIIb300-312), only inhibits the binding of 4A5, and does not
      affect the binding of the anti-Fg-RIBS-I to Fg. The anti-Fg-RIBS-I reduces the on
      rate of the 4A5 binding to Fg with no measurable changes in the dissociation of
      the Fg-bound 4A5. These data indicate that the inhibition of platelet aggregation
      and adhesion by the anti-Fg-RIBS-I antibody is due to the steric hindrance of the
      Fg gamma400-411 to platelet GPIIbIIIa. Thus the Fg RIBS-I epitope (gamma373-385)
      does not appear to be involved in direct interaction with platelet GPIIbIIIa,
      leaving the gamma408-411 of Fg as the sole domain mediating platelet aggregation
      and adhesion.

PMID- 9920399
TI  - Control of mitochondrial beta-oxidation: sensitivity of the trifunctional protein
      to [NAD+]/[NADH] and [acetyl-CoA]/[CoA].
AB  - Isolated human mitochondrial trifunctional protein was incubated with 2
      hexadecenoyl-CoA, CoA and NAD+ and the resultant CoA esters measured. Steady
      state with respect to the concentrations of the intermediates 3
      hydroxyhexadecanoyl-CoA and 3-ketohexadecanoyl-CoA and the rate of formation of
      the product tetradecanoyl-CoA was reached within 4 min. Flux was greatly enhanced
      by the addition of Tween 20 (0.2% v/v) which stimulated 3-ketoacyl-CoA thiolase
      activity by over 7-fold. When 3-ketoacyl-CoA thiolase was not stimulated, 3
      hydroxyhexadecanoyl-CoA was the prominent CoA ester accumulated, presumably due
      to inhibition of 3-hydroxyacyl-CoA dehydrogenase activity by accumulated 3
      ketoacyl-CoA, analogous to the inhibition of short-chain 3-hydroxyacyl-CoA
      dehydrogenase by 3-ketoacyl-CoA. When [NAD+]/[NADH] was varied at a fixed total
      [NAD++NADH], the overall flux was only inhibited by [NAD+]/[NADH] less than 1. In
      contrast, when [acetyl-CoA]/[CoA] was varied at a fixed total [CoA], much greater
      sensitivity was observed.

PMID- 9920400
TI  - Isolation, properties and N-terminal amino acid sequence of a factor V activator
      from Vipera lebetina (Levantine viper) snake venom.
AB  - A factor V activator (VLFVA) was separated from Vipera lebetina venom by gel
      filtration on Sephadex G-100 superfine, followed by chromatography on CM
      cellulose and on heparin-agarose. This enzyme (VLFVA) with a molecular mass of
      28.4 kDa, as determined by matrix assisted laser desorption ionization time-of
      flight mass spectrometry, is a single-chain glycoprotein containing seven
      residues of neutral sugars, seven residues of hexosamines and three residues of
      neuraminic acid per molecule. The treatment with N-glycosidase F lowered the
      molecular mass approximately 6%. The N-terminal sequencing of VLFVA up to the
      30th residue evidenced a high homology with Vipera russelli factor V activator
      RVV-Vgamma (90% identity). Aside from factor V, no other protein substrate for
      VLFVA has yet been identified. VLFVA hydrolyzes several synthetic arginine ester
      substrates, such as benzoylarginine ethyl ester (BAEE), tosylarginine methyl
      ester (TAME) and amide substrates such as Pro-Phe-Arg-MCA. The arginine ester
      hydrolase activity of the enzyme is markedly lower than that of the crude venom.
      The ability of VLFVA to activate factor V and its activity to BAEE and TAME were
      inhibited by the serine proteinase inhibitor, diisopropylfluorophosphate. VLFVA
      is thermostable protein, heating for 20 min at 70 degrees C does not alter the
      arginine esterase activity of the enzyme.

PMID- 9920401
TI  - Threonine 82 in the regulatory chain is important for nucleotide affinity and for
      the allosteric stabilization of Escherichia coli aspartate transcarbamoylase.
AB  - The three-dimensional structure of Escherichia coli aspartate transcarbamoylase
      complexed with the allosteric effector CTP, shows an interaction between the
      hydroxyl of Thr-82 in the regulatory chain (Thr-82r) with the gamma-phosphate of
      CTP (R.P. Kosman, J.E. Gouaux, W.N. Lipscomb, Crystal structure of CTP-ligated T
      state aspartate transcarbamoylase at 2.5 A resolution: implications for aspartate
      transcarbamoylase mutants and the mechanism of negative cooperativity, Proteins
      Struct. Funct. Genet. 15 (1993) 147-176). In order to determine whether the Thr
      82r interaction with the gamma-phosphate of CTP is important for either binding
      of the nucleotide effectors or their function, site-specific mutagenesis was
      employed. The mutant enzyme in which Thr-82r was replaced by Ala had almost the
      identical maximal observed specific activity as the wild-type enzyme; however,
      the mutant enzyme had a significantly increased [Asp]0.5, the aspartate
      concentration at one-half the maximal observed specific activity, as well as
      slightly increased homotropic cooperativity. The mutant enzyme was also activated
      more by ATP and inhibited less by CTP as compared to the wild-type enzyme. In
      addition, the nucleotide concentration required for one-half maximal effect was
      increased approx. 3-fold as compared to the corresponding values for the wild
      type enzyme. The maximal inhibition of the mutant enzyme, in the presence of UTP
      and CTP was similar to that observed for the wild-type enzyme; however, higher
      concentrations of the nucleotides were required to achieve this level of
      inhibition. The reduced affinity of CTP, UTP and ATP induced by the mutation
      indicates that the hydrogen bonding interaction between the gamma-phosphate of
      the nucleotide effector and the side-chain hydroxyl of Thr-82r is important for
      the binding of the nucleotide effectors to the allosteric site. Furthermore, this
      interaction is important for the discrimination between CTP and CDP. Finally, the
      greater homotropic cooperativity, greater [Asp]0.5, diminished CTP inhibition and
      greater ATP activation of the mutant enzyme correlates with the X-ray structure
      of the mutant enzyme which shows that the unligated enzyme is in an 'extreme' T
      state. These findings add support to the theory that the global stabilization of
      the enzyme is critical for both the homotropic and heterotropic properties of
      aspartate transcarbamoylase.

PMID- 9920402
TI  - Amoebapore homologs of Caenorhabditis elegans.
AB  - It is shown that the Caenorhabditis elegans genome contains several distantly
      related members of the gene family of saposin-like proteins. The putative
      products of genes T07C4.4, T08A9.7A, T08A9.7B, T08A9.8, T08A9.9, T08A9.10 are
      similar to the amoebapores of Entamoeba histolytica, granulysin of cytotoxic T
      lymphocytes and a putative amoebapore-related protein of the liver fluke Fasciola
      hepatica inasmuch as they consist of only a single saposin-like domain and a
      secretory signal peptide. The saposin-like domain of protein T07C4.4, which is
      most closely related to NK-lysin and granulysin, has been expressed in
      Escherichia coli and the recombinant protein was shown to have a circular
      dichroism spectrum consistent with the helix bundle structure characteristic of
      saposin-like domains. Recombinant T07C4.4 protein was found to have antibacterial
      activity, suggesting that these amoebapore homologs may play a role in
      antibacterial mechanisms of C. elegans.

PMID- 9920403
TI  - Thiol-disulfide redox buffers maintain a structure of immunoglobulin A that is
      essential for optimal in vitro binding to secretory component.
AB  - We have shown that human secretory component (SC) binds in vitro to different
      samples of human and murine dimeric immunoglobulin A (IgA). The binding ratio in
      the IgA/SC complex is 1:1. IgA which is stably bound to SC is separated from
      unreacted IgA by anion exchange chromatography. A part of IgA/SC complexes formed
      in vitro is unstable to this elution; the proportion varies between different
      samples of IgA; it increases following prolonged incubation of IgA at 37 degrees
      C. Incubation of IgA with glutathione/glutathione disulfide (GSH/GSSG) redox
      buffers increases the proportion able to form a stable complex with SC to
      approximately 90%. The presence of bound SC is not essential for this process but
      does allow it to occur at a lower GSH/GSSG concentration. The stable IgA/SC
      complex consists of a structure with a disulfide bond between IgA and SC
      apparently in equilibrium with a structure in which this bond is absent. The
      proportion bound covalently is similar for different samples of IgA and is
      insensitive to incubation with GSH/GSSG. It is significantly greater for
      secretory IgA (sIgA) and for IgA and SC incubated together with a starting
      mixture of cysteine/cystine. Monoclonal, antigen-specific IgA, all of which is
      optimally bound to SC in essentially the same way as in native sIgA, can be
      isolated in high yield. Our results support a mechanism for optimal binding of
      IgA to SC, that can occur both in vitro and in vivo, in which a thiol disulfide
      interchange occurs between a free IgA thiol and a sensitive SC disulfide
      following the initial non-covalent interaction.

PMID- 9920404
TI  - Involvement of essential cysteine and histidine residues in the activity of
      isolated glutaminase from tumour cells.
AB  - The pH dependence of the phosphate-activated glutaminase isolated from Ehrlich
      tumour cells suggests a functional role for two prototropic groups with apparent
      pKa of 9.3 and 7.7 at the active site of the protein; these pKa values are
      compatible with cysteine and histidine residues, respectively. This possibility
      was investigated by chemical modification studies of the purified enzyme. N
      Ethylmaleimide fully inactivated the purified glutaminase; the reaction order was
      very close to 1.0, suggesting that N-ethylmaleimide modifies glutaminase at a
      single essential site. Spectrophotometric studies of the isolated protein treated
      with diethyl pyrocarbonate indicate that two histidine residues are modified.
      Since glutaminase is loosely associated to the inner mitochondrial membrane,
      modification experiments were also carried out using mitochondrial membrane
      fractions. N-Ethylmaleimide and diethyl pyrocarbonate gave similar results in
      mitochondria membrane-bound enzyme to those obtained with purified enzyme.
      Glutamate, which behaves as a competitive inhibitor of the enzyme, partially
      protected the inactivation caused by N-ethylmaleimide in membrane-bound
      experiments. The results suggest the existence of a critical histidine residue(s)
      in the tumour glutaminase, and strongly support the notion that a cysteine
      residue, which is located at (or near) the active site, is involved in the
      catalytic mechanism as well.

PMID- 9920405
TI  - Cloning and bacterial expression of adenosine-5'-triphosphate sulfurylase from
      the enteric protozoan parasite Entamoeba histolytica.
AB  - A gene encoding adenosine-5'-triphosphate sulfurylase (AS) was cloned from the
      enteric protozoan parasite Entamoeba histolytica by polymerase chain reaction
      using degenerate oligonucleotide primers corresponding to conserved regions of
      the protein from a variety of organisms. The deduced amino acid sequence of E.
      histolytica AS revealed a calculated molecular mass of 47925 Da and an unusual
      basic pI of 9.38. The amebic protein sequence showed 23-48% identities with AS
      from bacteria, yeasts, fungi, plants, and animals with the highest identities
      being to Synechocystis sp. and Bacillus subtilis (48 and 44%, respectively). Four
      conserved blocks including putative sulfate-binding and phosphate-binding regions
      were highly conserved in the E. histolytica AS. The upstream region of the AS
      gene contained three conserved elements reported for other E. histolytica genes.
      A recombinant E. histolytica AS revealed enzymatic activity, measured in both the
      forward and reverse directions. Expression of the E. histolytica AS complemented
      cysteine auxotrophy of the AS-deficient Escherichia coli strains. Genomic
      hybridization revealed that the AS gene exists as a single copy gene. In the
      literature, this is the first description of an AS gene in Protozoa.

PMID- 9920406
TI  - Calcium: outside/inside homeostasis and signalling.
AB  - More and more data accumulate concerning calcium dependent effects in all
      compartments of cells. The higher the organism in evolution the more calcium
      becomes involved. Inspection of the data while looking for an explanation of the
      involvement of calcium in metabolism, nuclear functions, control over pumps,
      external activities, mineralisation and so on leads one to suppose that calcium
      has an integrating function. The implication is that calcium flow is a large
      network connecting the environment, the cytoplasm, vesicles, organelles, the
      nucleus and in higher species, organs. There is the possibility then that calcium
      ion functions are being analysed, often in vitro, in a bit by bit reductionist
      manner while in vivo calcium is the equivalent of an electron in complicated
      electrical circuits. We then should look for its connections to energy, to
      effects where conformational switching by calcium pulses is equivalent to
      magnetic triggering by electron flow and where storage in vesicles is equivalent
      to condenser-like devices and so on. The appearance of pulsing, of time delays in
      parts of circuits, and other properties of electronic circuits seen in calcium
      triggering are then explicable as part of calcium circuit design. No other ion
      can operate in the same way due to the peculiarities of the calcium ion, its
      size, charge, ionisation potential and its availability which allow it both to
      flow rapidly yet to bind considerably.

PMID- 9920407
TI  - Disorders of the calcium-sensing receptor.
AB  - The human calcium-sensing receptor (CaSR) is a 1078-amino-acid cell surface
      protein which is expressed in the parathyroids, thyroid cells and the kidney, and
      is a member of the family of G protein-coupled receptors. The CaSR allows
      regulation of parathyroid hormone (PTH) secretion and renal tubular calcium
      reabsorption in response to alterations in extracellular calcium concentrations.
      The human CaSR gene is located on chromosome 3q13.3-q21, and loss of function
      CaSR mutations have been reported in the hypercalcaemic disorders of familial
      benign (hypocalciuric) hypercalcaemia (FBH or FHH) and neonatal severe primary
      hyperparathyroidism (NSHPT). In addition, gain of function CaSR mutations have
      been observed in a novel familial syndrome of hypocalcaemia with hypercalciuria.
      The human CaSR gene on chromosome 3q13.3-q21 is likely to be one of several, as
      two other loci for FBH have been located on chromosome 19p and 19q13. Cloning and
      characterisation of these genes will help to further elucidate the mechanisms
      regulating extracellular calcium.

PMID- 9920408
TI  - Points of convergence between Ca2+ and Ras signalling pathways.
AB  - p21 Ras proteins play a critical role in the regulation of cellular growth and
      differentiation. In addition, Ras and proteins which regulate Ras activity have
      been implicated in long-term memory consolidation and long-term potentiation
      processes. Over the last few years, much evidence has emerged which indicates
      that changes in cytoplasmic Ca2+ levels can regulate Ras protein activity and
      subsequent biological function. Also, Ras proteins themselves can modulate
      intracellular Ca2+ levels by regulating both Ca2+ release and Ca2+ influx
      processes. Here we examine the signalling components which regulate Ras activity
      and, in particular, consider points of convergence between intracellular Ca2+ and
      p21 Ras signalling processes. In addition, we consider the possible biological
      consequences resulting from the integration of these signalling pathways and
      highlight the importance of our understanding protein protein interactions.
      Finally, we discuss the possibility of protein-protein interactions mediated via
      Ca2+-responsive structural domains, such as the C2 and IQ domains, playing
      important roles in Ca2+-dependent Ras functions yet to be established.

PMID- 9920409
TI  - Calmodulin-dependent protein kinase IV: regulation of function and expression.
AB  - Calmodulin-dependent protein kinase IV (CaMKIV) is a key mediator of Ca2+-induced
      gene expression. This serine/threonine kinase is itself activated by a calmodulin
      kinase kinase. In the present contribution the gene structure, regulation of
      activity, the role in Ca2+-dependent gene expression, and the hormonal induction
      and controlled expression of CaMKIV during tissue development are reviewed.

PMID- 9920410
TI  - Calcium-binding protein S100A4 in health and disease.
AB  - The S100 proteins contain two EF-hand motifs and are of generally unknown
      function. One of these proteins, S100A4, is an intracellular calcium-binding
      protein that is present in normal rodent and human cells. In cultured rodent
      mammary cells, S100A4 is expressed at a higher level in some metastatic
      epithelial cells than in non-metastatic counterparts. Similarly, in human breast
      cell lines, S100A4 is present at a higher level in cultured cells from the more
      malignant, than in those from the more benign tumours. Gene transfer experiments
      have shown that rodent or human S100A4 is able to induce metastatic capability in
      otherwise non-metastatic breast tumour cells. Furthermore, expression of rodent
      S100A4 transgenes can induce metastasis of benign tumours arising in transgenic
      model systems. Possible mechanisms for the metastasis-inducing effect of S100A4
      and the relevance of these observations to human cancer are discussed.

PMID- 9920411
TI  - Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9).
AB  - The two migration inhibitory factor- (MIF)-related protein-8 (MRP8; S100A8) and
      MRP14 (S100A9) are two calcium-binding proteins of the S100 family. These
      proteins are expressed during myeloid differentiation, are abundant in
      granulocytes and monocytes, and form a heterodimeric complex in a Ca2+-dependent
      manner. Phagocytes expressing MRP8 and MRP14 belong to the early infiltrating
      cells and dominate acute inflammatory lesions. In addition, elevated serum levels
      of MRP8 and MRP14 have been found in patients suffering from a number of
      inflammatory disorders including cystic fibrosis, rheumatoid arthritis, and
      chronic bronchitis, suggesting conceivable extracellular roles for these
      proteins. Although a number of possible functions for MRP8/14 have been proposed,
      the biological function still remains unclear. This review addresses recent
      developments regarding the MRP14-mediated promotion of leukocyte-endothelial cell
      interactions and the characterization of MRP8/14 heterodimers as a fatty acid
      binding protein complex. In view of the current knowledge, the authors will
      hypothesize that MRP8 and MRP14 play an important role in leukocyte trafficking,
      but do not affect neutrophil effector functions.

PMID- 9920412
TI  - Calcium signalling in Bacillus subtilis.
AB  - Few systematic studies have been devoted to investigating the role of Ca2+ as an
      intracellular messenger in prokaryotes. Here we report an investigation on the
      potential involvement of Ca2+ in signalling in Bacillus subtilis, a Gram-positive
      bacterium. Using aequorin, it is shown that B. subtilis cells tightly regulate
      intracellular Ca2+ levels. This homeostasis can be changed by an external
      stimulus such as hydrogen peroxide, pointing to a relationship between oxidative
      stress and Ca2+ signalling. Also, B. subtilis growth appears to be intimately
      linked to the presence of Ca2+, as normal growth can be immediately restored by
      adding Ca2+ to an almost non-growing culture in EGTA containing Luria broth
      medium. Addition of Fe2+ or Mn2+ also restores growth, but with 5-6 h delay,
      whereas Mg2+ did not have any effect. In addition, the expression of alkyl
      hydroperoxide reductase C (AhpC), which is strongly enhanced in bacteria grown in
      the presence of EGTA, also appears to be regulated by Ca2+. Finally, using 45Ca2+
      overlay on membrane electrotransferred two-dimensional gels of B. subtilis, four
      putative Ca2+ binding proteins were found, including AhpC. Our results provide
      strong evidence for a regulatory role for Ca2+ in bacterial cells.

PMID- 9920413
TI  - Membrane domain formation by calcium-dependent, lipid-binding proteins: insights
      from the C2 motif.
AB  - We propose a novel role in cellular function for some membrane-binding proteins
      and, specifically, the C2 motif. The C2 motif binds phospholipid in a manner that
      is modulated by Ca2+ and is thought to confer membrane-binding ability on a wide
      variety of proteins, primarily proteins involved in signal transduction and
      membrane trafficking events. We hypothesize that in the absence of Ca2+ the C2
      motif couples the free energy of binding to a bilayer membrane comprised of
      zwitterionic and negatively charged lipids to the formation of a domain enriched
      in the negative lipids. This in turn leads to the dynamic clustering of bound
      homologous or heterologous proteins incorporating the C2 motif, or other acidic
      lipid-binding motifs. In the presence of Ca2+, the protein clusters may be
      further stabilized. In support of this hypothesis we present evidence for
      membrane domain formation by the first C2 domain of synaptotagmin in the absence
      of Ca2+. Fluid state phospholipid mixtures incorporating a pyrene-labeled
      phospholipid probe exhibited a change in pyrene excimer/monomer fluorescence
      ratio consistent with domain formation upon binding the C2 domain. In addition,
      we present the results of simulations of the interaction of the C2 domain with
      the membrane that indicate that protein clusters and lipid domains form in
      concert.

PMID- 9920414
TI  - The fork head transcription factor Hcm1p participates in the regulation of
      SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole
      body.
AB  - We previously identified HCM1 as a dosage-dependent suppressor of a calmodulin
      temperature-sensitive mutant (cmd1-1). Calmodulin performs multiple functions in
      yeast. Here we demonstrate that the effects of HCM1 are specific to the role of
      calmodulin at the spindle pole body. Overexpression of HCM1 fully suppresses the
      temperature sensitivity of a calmodulin mutant (cmd1-3) that only has defects in
      assembly of the spindle pole body but does not suppress the temperature
      sensitivity of a calmodulin mutant (cmd1-8) that only affects other functions of
      calmodulin. The DNA binding specificity of Hcm1p was determined by a selection,
      amplification and binding protocol. The consensus sequence for an Hcmlp binding
      site is WAAYAAACAAW. Mutations in the DNA binding domain of Hcm1p abolish the
      ability of Hcmlp to specifically recognize this binding site and abolish the
      ability of Hcm1p to act as a suppressor of calmodulin mutants. The promoter of
      SPC110 contains a match to the consensus binding site. Deletion of HCM1 does not
      affect the basal level of SPC110 transcription, but reduces the induction that
      occurs late in G1 of the cell cycle.

PMID- 9920415
TI  - Temporal inhibition of calmodulin in the nucleus.
AB  - Calmodulin (CaM) acts as a primary mediator of calcium signaling by interacting
      with target proteins. We have previously shown that nuclear CaM is critical for
      cell cycle progression using a transgene containing four repeats of a CaM
      inhibitor peptide and nuclear targeting signals (J. Wang et al., J. Biol. Chem.
      270 (1995) 30245 30248; Biochim. Biophys. Acta 1313 (1996) 223-228). To evaluate
      the role of CaM in the nucleus specifically during S phase of the cell cycle, a
      motif which stabilizes the mRNA only during S phase was included in the
      transgene. The CaM inhibitor mRNA transcript contains a self-annealing stem-loop
      derived from histone H2B at the 3' end. This structure provides stability of the
      mRNA only during S phase, thereby restricting CaM inhibitor expression to S
      phase. The inhibitor accumulates in the nucleus, particularly in the nucleoli.
      Flow cytometric analysis demonstrated that the CaM inhibitor is expressed in S
      and G2. Transfected cells show growth inhibition and a reduction in DNA
      synthesis. The CaM inhibitor peptide is a versatile reagent that allows spatial
      as well as temporal dissection of calmodulin function.

PMID- 9920416
TI  - Clustered organization of S100 genes in human and mouse.
AB  - S100 Ca2+-binding proteins became of major interest because of their differential
      expression in tissues and their association with human diseases. Earlier studies
      showed that 13 S100 genes are located as a cluster on human chromosome 1q21.
      Since a number of mouse S 100 genes, such as S100A4 and S100A6, have been
      localized to a syntenic region on mouse chromosome 3, we investigated if the S100
      gene cluster exists in mouse and is structurally conserved during evolution.
      First we identified the cDNA sequences of mouse S100A1, S100A3 and S100A5. Then
      we isolated a 490 kb mouse YAC clone which gives a specific signal by FISH most
      likely on chromosome 3. Hybridization studies with different mouse S100 cDNAs
      revealed that eight mouse S100 genes are arranged in a clustered organization
      similar to that in human. The linkage relationships between the genes S100A8
      S100A9 and S100A3-S100A4-S100A5-S100A6 were conserved during divergence of human
      and mouse about 70 million years ago. However, the separation of the mouse S100
      genes S100A1 and S100A13 in comparison to the human linkage group suggests
      rearrangement processes between human and mouse. Our data demonstrate that the
      S100 gene cluster is structurally conserved during evolution. Further studies on
      the genomic organization of the S100 genes including various species could
      generate new insights into gene regulatory processes and phylogenetic
      relationships.

PMID- 9920417
TI  - Probing the structure of the human Ca2+- and Zn2+-binding protein S100A3:
      spectroscopic investigations of its transition metal ion complexes, and three
      dimensional structural model.
AB  - A large-scale procedure was developed for the anaerobic purification of the human
      recombinant Ca2+- and Zn2+-binding protein S100A3 for spectroscopic studies.
      S100A3 eluted as a non-covalently bound dimer (20.8 kDa). It contained 7.5+/-0.1
      free thiol groups/monomer, and bound Ca2+ with a Kd of approximately 4 mM, which
      corresponds to a tenfold increase in affinity compared to the aerobically
      purified protein. The transition metal ions Co2+, Zn2+ and Cd2+ were used as
      spectroscopic probes to investigate the role of the 10 cysteine residues per
      monomer S100A3 in metal binding. Spectrophotometric titrations suggest the
      formation of dinuclear thiolate-bridged clusters consisting of a Me2+(S(Cys))4
      and a Me2+(S(Cys))3(N(His)) site as described for zinc finger proteins. A three
      dimensional structural model of S100A3 was proposed on the basis of the NMR
      structure of the structurally related rabbit S100A6 protein, and taking into
      account the structural influence of cysteine residues.

PMID- 9920418
TI  - Association of S100B with intermediate filaments and microtubules in glial cells.
AB  - Previous in vitro studies have shown that the Ca2+-regulated S100B protein
      modulates the assembly-disassembly of microtubules (MTs) and type III
      intermediate filaments (IFs). In the present report, by double immunofluorescence
      cytochemistry S 100B was localized to both GFAP/vimentin IFs and MTs as well as
      to centrosomes in U251 glial cells. In cells treated with the MT-depolymerizing
      agent, colchicine, S100B remained associated with the rearranged GFAP IFs
      throughout the cell and, at the cell periphery, vimentin IFs. In cells treated
      with the MT stabilizing agent, taxol, S100B followed partly the rearrangement of
      MTs and partly the rearrangement of IFs. Under the latter condition, bundles of
      MTs with their associated S100B appeared surrounded and/or flanked by rearranged
      IFs with their associated S100B. Colocalization of S100B with closely arranged
      IFs and MTs was best evident in cells manipulated with taxol and in triton
      cytoskeletons. In these cases, MTs and their associated S100B appeared surrounded
      and/or flanked by and/or intermingled with IFs and their associated S100B. Also,
      a preferential association of S100B with GFAP vs. vimentin IFs could be observed
      near the nucleus where colocalization of S100B with MTs was also maximal.
      Condensation of IFs and alteration of the MT network caused by treatment of cells
      with the phosphatase inhibitor, okadaic acid, resulted in a concomitant
      condensation/alteration of the S100B immunoreactivity. The present results lend
      support to the possibility that S100B may be an important factor implicated in
      the regulation of the dynamics of MTs and IFs.

PMID- 9920419
TI  - The identification and differential expression of calcium-binding proteins
      associated with ocular melanoma.
AB  - Calcium-binding proteins may endow tumor cells with properties related to their
      malignancy and metastatic phenotype. Chromatographic procedures and amino acid
      sequence analysis were used in this study to identify seven calcium-binding
      proteins, annexin VI, cap g, annexin V, calmodulin, S100A11, S100B and S100A6,
      associated with uveal melanoma, the primary ocular tumor of adults. This series
      of calcium-binding proteins was identified in both primary tumors and cell lines
      of uveal melanoma. Several of the proteins were shown by immunochemical methods
      to be differentially expressed between normal uveal melanocytes and malignant
      melanomas of the uvea. In addition, the expression of S100A6 may correlate with
      the malignant properties of the tumor.

PMID- 9920420
TI  - Characterisation of calcium signalling in DT40 chicken B-cells.
AB  - The chicken DT40 pre-B-cell line is becoming a potent experimental tool in the
      elucidation of higher organism cellular functions due to its unique genetic
      tractability. While several publications have described the effects of disruption
      of a range of genes in DT40 cells on calcium signalling, there has been no
      general overview of Ca2+ responses in wild-type cells. Here, we present
      experimental data comparing and contrasting the calcium responses to a range of
      agonists, such as alphaIgM, H2O2 and thapsigargin, applied singly or
      consecutively in the presence or absence of extracellular calcium. Briefly, we
      show that calcium release is from thapsigargin-sensitive and also -insensitive
      stores. This release results in, or is concomitant with, calcium entry across the
      plasma membrane through store-operated, receptor-operated and possibly L-type
      like Ca2+ channels. The agonists activate these pathways differentially producing
      a wide range of different sized and shaped Ca2+ signals. Furthermore, we report
      that Ca2+ responses in DT40 cells are dependent on the growth conditions. The
      presence of 1% chicken serum in the growth medium increased amplitudes of calcium
      responses and enhanced the sustained phase of the alphaIgM response, while 10
      microM beta-mercaptoethanol in the medium (not, however, present during calcium
      measurements) resulted in more transient H2O2 responses and larger amplitude
      alphaIgM responses while failing to affect thapsigargin responses. The possible
      causes of these effects and their importance in comparing data from different
      studies on DT40 cells is discussed.

PMID- 9920421
TI  - Phospholipid vesicle binding and aggregation by four novel fish annexins are
      differently regulated by Ca2+.
AB  - Four members of the annexin family, herein referred to as max (for medaka
      annexin) 1-4, have recently been identified through hybridization cloning in the
      killifish Oryzias latipes (D. Osterloh, J. Wittbrodt and V. Gerke,
      Characterization and developmentally regulated expression of four annexins in the
      killifish medaka. DNA and Cell Biol., in press). These annexins which are
      expressed in a developmentally regulated manner are present as a maternal pool in
      unfertilized eggs of another fish species, Misgurnus fossilis, and it has been
      proposed that they play a role in the Ca2+-regulated exocytosis of cortical
      granules occurring after fertilization. To characterize biochemical properties of
      the medaka proteins possibly relevant to their function in early development, we
      analyzed the ability of recombinantly expressed max 1-4 to interact with the
      principal structures of the egg cortex, phospholipid membranes and actin
      filaments. We show that all medaka annexins bind to acidic phospholipids in a
      Ca2+-regulated manner, although exhibiting different Ca2+ sensitivities. All
      medaka annexins, but max 1, are also capable of inducing, in a Ca2+-dependent
      manner, phospholipid vesicle aggregation, albeit only max 3 displays this
      activity at Ca2+ concentrations met in stimulated (i.e. fertilized) eggs. Max 3
      is also the only medaka annexin able to interact with F-actin in the presence of
      Ca2+. These data identify by biochemical criteria max 3 as a close relative of
      the mammalian annexins I and II, thus supporting previous sequence-based
      comparisons. Max 3 is therefore the prime annexin candidate for being involved in
      cortical granule exocytosis, possibly by providing granule granule, granule
      plasma membrane and/or granule cytoskeleton contacts.

PMID- 9920422
TI  - The environmental and health effects of solar radiation.

PMID- 9920423
TI  - The measurement of solar ultraviolet radiation.
AB  - High skin cancer rates, stratospheric ozone depletion and increased public
      interest and concern have resulted in a strong demand for solar ultraviolet
      radiation measurements and information. The Australian Radiation Laboratory (ARL)
      has been involved since the mid-1980s in the measurement of solar ultraviolet
      radiation (UVR) using spectroradiometers (SRM) and a network of broadband
      detectors at 18 sites in Australia and Antarctica and in Singapore through a
      collaborative agreement with the Singapore Institute of Science and Forensic
      Medicine. Measurement locations range from equatorial (Singapore, 1.3 degrees N)
      through tropical (Darwin, 12.4 degrees S) to polar (Mawson, 67.6 degrees S) and
      as a result there are many difficulties associated with maintenance and
      calibration of the network detectors, and transfer of data to ensure an accurate
      and reliable data collection. Calibration procedures for the various detectors
      involve the comparison with simultaneous spectral measurements using a portable
      SRM incorporating a double monochromator, calibrated against traceable standard
      lamps. Laboratory measurements of cosine response and responsivity are also made.
      Detectors are intercompared at the Yallambie site for a number of months before
      installation at another location. As an additional check on the calibrations,
      computer models of solar UVR at the earth's surface for days with clear sky and
      known ozone are compared with the UV radiometer measurements.

PMID- 9920424
TI  - Protection against solar ultraviolet radiation.
AB  - Interest in protection against solar ultraviolet radiation (UVR) among the
      general public in Australia has been increasing steadily as a result of the
      'SunSmart' campaigns run by the various state cancer councils. This increasing
      awareness is due in part to the requirements for occupational protection of
      outdoor workers and to provision of UVR protection for the recreational market.
      Behaviour outdoors can significantly affect exposure to solar UVR and use of
      items of personal protection can provide a substantial reduction in the UVR dose
      received. The protective properties of sunscreens, sunglasses, hats and clothing
      against UVR have been the subject of considerable research for some time, and
      over the last few years interest has extended to the provision of shade
      structures and the UVR protection provided by various commonly used materials.
      These materials include shadecloth, plastics, glass, windscreens and applicable
      tints. Australia has rigorous standards covering protection and UVR, in
      particular for sunscreens [Standards Australia/Standards New Zealand, Sunscreen
      products-evaluation and classification, Report No. AS 2604, Sydney/Wellington,
      1993.], sunglasses [Standards Australia, Sunglasses and fashion spectacles
      nonprescription types, Report No. AS 1067.1, Sydney, 1990.], protective eyewear
      [Standards Australia/Standards New Zealand, Eye protectors for industrial
      applications, Report No. AS/NZS 1337, Sydney/Wellington, 1992.] and shadecloth
      [Standards Australia, Synthetic shadecloth, Report No. AS 4174, Sydney, 1994.].
      Compliance with the sunglass standard became mandatory in 1988 and UVR protection
      provided by sunglasses has increased substantially since then. In July 1996 a
      standard on 'sun protective textiles' [Standards Australia/Standards New Zealand,
      Sun protective clothing-evaluation and classification, Report No. AS/NZS 4399,
      Sydney, 1996.] incorporating ultraviolet protection factors (UPFs) and a rating
      scheme with protection categories, was introduced; this was the first of its kind
      in the world. Australian Radiation Laboratory (ARL) UPF swing tags with UVR
      protection advice from the Australian Cancer Society on the reverse side are used
      to denote the amount of protection against solar UVR provided by clothing. To
      date in excess of 5 million ARL swing tags have been issued. Work on the various
      standards is continuing. The maximum allowed 'sun protection factor' (SPF) limit
      for sunscreens may be increased to SPF 30 + in the near future, and additions to
      the sun protective textiles standard are also planned. This paper discusses
      measurement methods, results, the rationale used in formulating the Australian
      Standards and the current state of UVR protection in Australia.

PMID- 9920425
TI  - UV-induced mutations and skin cancer: how important is the link?
AB  - Studies with patients having the inherited DNA repair disorders xeroderma
      pigmentosum (XP), Cockayne syndrome (CS), and sun-sensitive trichothiodystrophy
      (TTD) have shown that neither the defect in repair nor the consequent elevated
      frequency of sunlight-induced mutations in the skin is sufficient to account for
      the classically high incidence of skin cancer in XP patients. The possible ways
      in which different mutations in the XP(D) gene and deficiencies in the immune
      system may be involved are discussed.

PMID- 9920427
TI  - Involvement of p16CDKN2A in cell cycle delays after low dose UV irradiation.
AB  - Ultraviolet (UV) radiation contributes to the aetiology of melanoma, but the
      precise mechanistic details are still unclear. The CDKN2A gene which is
      associated with familial and sporadic melanoma, encodes a tumour suppressor, p16.
      We have previously shown that in response to low doses of UV radiation the level
      of p16 increases, and that this correlates with a G2 delay. Here we report that
      in melanoma cell lines which do not express p16, or express a mutant p16, no G2
      delay is observed in response to UV. The loss of functional p16 also correlates
      with an increase in DNA damage as judged by increased numbers of bi- and
      multinuclear cells and cells containing 1-2 micronuclei following UV irradiation.
      This work provides a further link between UV radiation, CDKN2A and melanoma,
      suggesting that the functional inactivation of CDKN2A disrupts a p16-dependent G2
      cell cycle checkpoint, thus contributing to the development of this neoplasm.

PMID- 9920426
TI  - UVB-specific regulation of gene expression in human melanocytic cells: cell cycle
      effects and implication in the generation of melanoma.
AB  - Analysis of the expression of a number of known genes in cultured human cells has
      revealed UVB-induced changes that may be specific for melanocytic cells. The
      response of c-fos, p53 and HIV-LTR reporter constructs to UVB and UVC was reduced
      in MM96L melanoma cells compared to HeLa. Cell cycle arrest produced by UVA,
      gamma radiation, cisplatin or the antimetabolite deoxyinosine differed from that
      of UVB. Cell cycle analysis after multiple doses of UVB raised the possibility
      that UVB-induced pRb depletion could result in increased mutation and thus
      enhanced tumourigenesis of irradiated melanocytes in skin subjected to a defined
      pattern of UVB exposure. To extend the analysis of gene expression in cultured
      melanocytic cells to uncharacterised genes, promoter trap cell clones containing
      unknown genes 'tagged' by a beta-galactosidase reporter construct were generated
      from MM96L cells. Altered gene expression in clones treated with a panel of DNA
      damaging agents was quantitated by measurement of beta-galactosidase activity. Of
      the clones containing 'tagged' endogenous promoters induced by UVB, 52% were
      induced only by UVB and not by other DNA-damaging agents (cisplatin, N-methyl-N
      nitro-nitrsoguanidine, fotemustine). One third of the clones were also activated
      by TPA suggesting that general DNA damage responses involving PKC are activated
      less frequently than unique pathways of gene activation. Overall, 60% of the 50
      clones that responded to the panel of agents were induced by only one of the
      agents, indicating that a high proportion of genes are induced by agent-specific
      mechanisms. In the long term, promoter trapping may allow the full repertoire of
      UVB-inducible genes to be characterised.

PMID- 9920429
TI  - Human pigmentation genes and their response to solar UV radiation.
AB  - Identification and characterisation of the genes involved in melanin pigment
      formation, together with the study of how their action is influenced by exposure
      to UV radiation, is providing a molecular understanding of the process of skin
      photoprotection through tanning. The mechanisms underlying this change in
      epidermal melanin involve both a transcriptional response of the pigmentation
      genes and post-translational control of the melanin biosynthetic pathway. UV rays
      are known to interact with numerous molecules within cells, and among these the
      photochemical reactions involving lipids and DNA are implicated in modulating
      melanogenesis. The combination of DNA damage, the formation of diacylglycerol,
      and the action of the melanocyte stimulating hormone receptor are all likely to
      be involved in UV-induced tanning.

PMID- 9920428
TI  - Effect of UV irradiation on cell surface protease activity and amino acid uptake.
AB  - The surface of most cells includes a coterie of resident proteins which act as
      receptors for a wide variety of ligands and other proteins which are potentially
      bioactive on cell-cell contact (juxtacrine effects), or else are released by
      enzyme activity to influence cell behaviour by autocrine or paracrine mechanisms.
      We previously found that UVC irradiation stimulates the release of TGFalpha from
      its membrane-bound preprocursor form whereby it acts as a stimulus to rapid,
      reparative cell multiplication; clearly this runs the risk hastening mitosis
      before UV-induced DNA damage is fully corrected, which in turn may increase the
      likelihood of residual lesions persisting and hence of new mutations being
      generated. We found that sublethal UVC irradiation (10 J m(-2)) of HeLa cell
      cultures also resulted in activation of ecto-aminopeptidase and ecto
      endopeptidases which were maximal 16 and 20-24 h after irradiation, respectively.
      Both of these classes of protease were shown to be metalloproteases using a
      nonapeptide substrate (called P9) which is cognate to the N-terminal cleavage
      site of preproTGFalpha except for a reporter 125I-tyrosine [Piva et al., J. Cell.
      Biochem. 64 (1997) 353-368]. We now show that the N-terminal tyrosine cleaved
      from P9 by cell surface aminopeptidase activity, was found to be taken up by the
      cell resulting in its 10-25-fold concentration intracellularly, some two- to
      threefold higher than from a reservoir source, and may represent a novel salvage
      pathway for recovery of essential amino acids. Aminopeptidase activity was found
      to be both temperature- and FBS-dependent but was not reliant on ATP for its
      activity. Tyrosine transport across the cell membrane was also temperature and
      FBS-dependent but required ATP for maximal activity. UVC irradiation enhanced
      aminopeptidase activity but not tyrosine uptake by the cultures. The fraction of
      HeLa cells undergoing apoptosis increased in those cultures which were exposed to
      higher doses of UVC. The levels of ecto-aminopeptidase and ecto-endopeptidase
      activity in apoptotic cells were elevated compared to viable cells receiving the
      same dose of UVC. These results suggest that increased levels of cell surface
      protease activity in apoptotic cells would increase the amounts of free amino
      acids and growth factors in the extracellular medium and hence stimulate the
      proliferation of surrounding cells to replace those killed by UV irradiation.

PMID- 9920430
TI  - Differences in the mutational specificities of sunlight and UVB radiation suggest
      a role for transversion-inducing DNA damage in solar photocarcinogenesis.
AB  - Mutations induced by UVB radiation and natural sunlight in a plasmid-borne yeast
      (Saccharomyces cerevisiae) tRNA gene (SUP4-o) were characterised by DNA
      sequencing. For both agents, the majority (> 90%) of the total mutations analysed
      were single base-pair substitutions, but tandem substitutions and single base
      pair deletions also were detected. Each agent induced all six types of base-pair
      change but the tandem substitutions involved exclusively G.C-->A.T transitions.
      However, the fractions of single and tandem G.C-->A.T transitions were reduced by
      about 50%, and the fraction of transversions at G.C pairs was increased by 11
      fold for sunlight relative to UVB. Comparisons of the site and strand
      specificities of the substitutions suggested that dipyrimidine adducts were
      responsible for the transitions, and that other lesions induced by sunlight may
      have given rise to the transversions. The relevance of these findings to skin
      cancer is discussed.

PMID- 9920431
TI  - Bacterial gene products in response to near-ultraviolet radiation.
AB  - Our research has focused on bacterial gene products that protect cells from
      damage by near-ultraviolet radiation (near-UV) including gene products involved
      in the subsequent recovery process. Protective gene products include such anti
      oxidants as catalases, superoxide dismutases and glutathione reductase. Near-UV
      damage recovery products include exonuclease III and DNA-glycosylases. Perhaps
      more critical than the products of structural genes are certain regulatory gene
      products that are triggered upon excess near-UV oxidation and lead to synthesis
      of entire batteries of anti-oxidant enzymes, DNA repair enzymes, and DNA
      integrity proteins. Our recent experiments have focused on RpoS and its
      interaction with OxyR, two proteins that regulate the synthesis of molecules that
      protect cells from near-UV and other oxidative stresses.

PMID- 9920432
TI  - Endogenous DNA methylation and epimutagenesis.

PMID- 9920433
TI  - Body site specific incidence of basal and squamous cell carcinoma in an exposed
      population, Townsville, Australia.
AB  - Most data on body site distribution of basal cell carcinoma (BCC) and squamous
      cell carcinoma (SCC) do not take into account the surface proportion occupied by
      body sites experiencing differing amounts of ultraviolet radiation. The recording
      of BCC and SCC is heterogenous and body sites are not standardized. This study
      was undertaken to assess the magnitude of the incidence rates of skin cancers at
      different body sites in a population which experiences high ultraviolet exposure
      and involved all primary care services in Townsville over 6 weeks in June 1993.
      The annual site-specific age-standardized (World Population) incidence rates of
      histologically diagnosed lesions, determined from data where lesions were
      recorded on a body map, were adjusted for surface area and expressed per 100,000
      body units (BU). Relative site densities of lesions were also calculated. Annual
      incidence rates for BCC per 100,000 BU on the most exposed face (ears, nose and
      cheeks) were 25,893 (95% confidence interval (c.i.) 18,837-32,950), 13,222 (95%
      c.i., 8273-18,171) on the less exposed face (forehead,eyebrow, chin and jaw) and
      27,837 (95% c.i., 12,560-43,115) on the least exposed face (area within the orbit
      and nasolabial fold). Incidence rates for SCC rates were highest on the less
      exposed face, 5843 (95% c.i., 2627-9058) most exposed face, 4200 (95% c.i., 1274
      7126) and the exposed upper limb, 3786 (95% c.i., 2783-4789). The relative site
      density of histologically confirmed BCC was 14 on the most exposed face in males
      compared with 5 in females and 11 around the eyes (least exposed) in males and 9
      in females compared with the body as a whole. Adjustment for body surface
      proportion demonstrates that highly exposed body sites are at very high risk. The
      magnitude of the incidence rates on these sites is attributed to the combination
      of a susceptible population and high ambient ultraviolet radiation (UVR).

PMID- 9920434
TI  - Glucose and related catabolite repressors are powerful inhibitors of pKM101
      enhanced UV mutagenesis in Escherichia coli.
AB  - When stationary phase Escherichia coli K12 trp (amber) cells were exposed to UV
      doses ranging from 180-540 J m(-2), we found that we could not recover any
      induced Trp+ revertants unless the irradiated cultures were first supplied with
      the Muc+ mutation-enhancing IncP plasmid pKM101 (by conjugation). We also found
      that the numbers of UV-induced Trp+ revertants recovered from pKM101+ cultures
      varied quite dramatically depending upon which of several commonly-used carbon
      sources were present in the post-irradiation plating medium, e.g., there were
      always significantly fewer revertants on minimal glucose plates than on minimal
      glycerol plates. More importantly, there were also fewer UV-induced revertants on
      glycerol + glucose plates than on 'glycerol-only' plates. We then tested two
      glucose-related compounds which are known to depress intracellular cyclic AMP
      (cAMP) levels even more effectively than glucose (glucose-6-phosphate and the non
      utilisable methyl-alpha-D-glucopyranoside) and found that they too were able to
      exert powerfully antimutagenic effects in UV-treated pKM101-containing bacteria.
      Taken together, these results provide strong additional support for our working
      hypothesis that at least one component of the mutational pathway which operates
      in UV-irradiated pKM101-containing cells is extremely sensitive to classical cAMP
      mediated catabolite repression.

PMID- 9920435
TI  - Melanoma is not caused by sunlight.
AB  - When comparisons are made of cutaneous melanoma with cutaneous squamous cell
      cancer (SCC) and basal cell cancer (BCC) of the skin with respect to age
      dependence, sex ratio, distribution on the body, association with sun exposure,
      and variation with latitude, it is clear that SCC is due almost entirely to sun
      exposure, that BCC is partly due to sun exposure, and that melanoma is not due to
      sun exposure. For melanoma, it is only latitudinal variation that favours the
      hypothesis of sun exposure causation. However, an examination of the latitudinal
      variation of SCC incidence reveals that this is several fold greater than can be
      accounted for by variation of exposure to UV-B. The other factor operating
      appears to be skin temperature. For melanoma, it is postulated that the latter
      factor by itself may suffice to account for the observed variation with latitude.
      The higher incidence of melanoma in the higher social classes and its increasing
      incidence with age may be readily explained by the hypothesis that melanoma
      incidence increases with increase in skin temperature.

PMID- 9920436
TI  - The impact of UVB radiation on marine plankton.

PMID- 9920437
TI  - UV-induced immunosuppression in virus infections.

PMID- 9920438
TI  - UVA-induced immunosuppression.
AB  - It has previously been demonstrated that chronic low-dose solar-simulated
      ultraviolet (UV) radiation can induce both local and systemic immunosuppression
      as well as tolerance to a topically applied hapten. Epidermal cells from UV
      irradiated mice inhibit spontaneous regression of tumours indicating that UV
      induced immunosuppression is likely to permit the outgrowth of developing UV
      induced skin tumours. We have used a chronic low-dose UV-irradiation protocol to
      investigate the effects of UVA on the skin immune system of C3H/HeJ mice.
      Irradiation with UVA + B significantly suppressed the local and systemic primary
      contact sensitivity (CS) response to the hapten TNCB. Furthermore UVA + B reduced
      Langerhans cell (LC) and dendritic epidermal T cell (DETC) numbers in chronically
      UV-irradiated mice. UVA-irradiation induced local, but not systemic,
      immunosuppression and reduced LC (32%) but not DETC from the epidermis compared
      to the shaved control animals. Treatment of mice with UVA + B or UVA radiation
      also induced an impaired secondary CS response, and this tolerance was
      transferable with spleen cells. Therefore exposure of C3H/HeJ mice 5 days per
      week for 4 weeks with UVA can induce local immunosuppression and tolerance. One
      of the mechanisms by which UVA affects biological systems is production of
      reactive oxygen species. We have also shown that Vitamin E, an inhibitor of lipid
      peroxidation, prevents UV-induced immunosuppression and loss of LC. It is
      possible that the UVA in UV radiation induces epidermal lipid peroxidation which
      stimulates LC migration from the epidermis, thus contributing to UV-induced
      immunosuppression. Hence, inhibition of epidermal lipid peroxidation by Vitamin E
      may provide some protection to the skin immune system from these effects of UV.

PMID- 9920439
TI  - Effects of UV on the migration and function of epidermal antigen presenting
      cells.
AB  - Depletion of epidermal Langerhans cells (LC) and the concomitant depression of
      the skin immune system after excessive exposure to ultraviolet B light (UVB) has
      been established in the international literature for some time. Our
      investigations were intended to determine whether or not these phenomena occurred
      as a direct result of increased LC migration being triggered by the UVB exposure.
      To test this hypothesis, a sheep model was established in which the lymphatic
      vessels draining a defined region of skin were cannulated and the cells migrating
      towards the regional lymph node continuously collected. Cell populations in these
      collections were identified and enumerated by indirect immunofluorescence and
      flow cytometry. These experiments showed there was a significant, dose-dependent
      increase in the rate of LC migration from sheep skin after exposure to doses of
      UVB light exceeding 1 minimal erythemal dose (MED). In a series of parallel
      experiments, the functional characteristics of dendritic cells (DC) migrating
      from normal or UVB irradiated sheep were studied. To assay them, enriched
      preparations of DC were collected via cannulated afferent lymphatic vessels and
      pulsed with antigen prior to incubation with autologous peripheral blood
      lymphocytes. The relative efficiency of antigen presentation was determined by
      the ability of DC to induce T cell proliferation. Our data clearly demonstrate
      that there is a profound loss of normal antigen-presenting cell function after
      exposure to UVB light. Various experiments were undertaken to determine the
      mechanism(s) associated with these changes in migration kinetics and cellular
      function. Electron microscopic examinations of LC migrating from normal or UVB
      irradiated skin have demonstrated a profound loss of dendritic processes after
      UVB exposure. This provides a possible explanation for the changes in skin
      immunity after UVB exposure.

PMID- 9920440
TI  - Photoprotection: sunscreens and the immunomodulatory effects of UV irradiation.
AB  - UV-B irradiation (UVR) of the host, in both humans and animal models, induces
      dose-related acute and chronic changes in skin which include erythema and
      photoageing, and induction of cancer. It can also induce modulation of immune
      responses of the host to antigens presented following irradiation. Commercially
      available, broad-spectrum, high SPF (15, 15 + ) sunscreens protect against most
      effects of UV irradiation. An exception is the effects of UVR on immune
      responsiveness, with varying degrees of protection having been reported. We
      examined a system of UV-induced systemic suppression of contact hypersensitivity
      (CHS) responses in BALB/c mice. A range of commercially-available, broad
      spectrum, high SPF (15 + ) sunscreens demonstrated at best partial protection
      against systemic immunosuppression, yet were able to protect against two
      hallmarks of acute UVR-induced damage: skin oedema and keratinocyte
      proliferation. Two major models have been identified for the induction of
      immunosuppression following UVR, one identifying trans-urocanic acid (trans-UCA;
      deaminated histidine, located in the stratum corneum) as the critical
      photoreceptor, the other featuring DNA. UVR of trans-UCA produces cis-UCA, which
      itself is immunomodulatory. There was some abrogation of trans to cis
      isomerisation of urocanic acid in UV-irradiated, sunscreen-protected mice.
      However, the majority of the immunomodulation seen in these mice was abrogated by
      pretreatment with a monoclonal antibody to cis-urocanic acid. It is possible to
      induce formation of cis-urocanic acid in BALB/c skin in the absence of
      immunosuppression, using lower doses of UV radiation, indicating that formation
      of cis-urocanic acid in the stratum corneum is not necessarily sufficient to
      induce immunosuppression in the UV-irradiated host. The mechanisms of induction
      of the immunomodulated state in the UV-irradiated host are potentially diverse
      and the subject of ongoing debate. Our studies maintain a role for cis-UCA, and
      form the basis for further studies on its involvement in immunomodulation by UVR
      in sunscreen-protected hosts.

PMID- 9920441
TI  - The effects of two UVB radiation-absorbing sunscreens on UV radiation-induced
      carcinogenesis, suppression of the contact hypersensitivity response and
      histological changes in the hairless mouse.
AB  - The research summarised in this report suggests that the two UVB-absorbers, o
      PABA and 2-EHMC, have different modes of protection against UV radiation-induced
      immunosuppression, carcinogenesis and histological alterations, that appear to be
      independent of their SPF values, within experimental limits. The UVB-absorber o
      PABA appears offer a valuable level of protection against photocarcinogenesis.

PMID- 9920442
TI  - Mechanisms of photosensitization by phototoxic drugs.

PMID- 9920443
TI  - Apparel textiles and sun protection: a marketing opportunity or a quality control
      nightmare?

PMID- 9920444
TI  - Influence of dietary factors on actinically-induced skin cancer.
AB  - The first indication that high dietary fat intake could influence the development
      of ultraviolet (UV) radiation-induced skin cancer in experimental animals was
      reported in 1939. In the 1980s a series of animal studies showed that a high
      level of dietary fat intake markedly shortened the time between UV exposure and
      tumor appearance and increased the number of tumors that developed. Further, high
      levels of dietary fat affected skin cancer development at the promotional stage
      of UV-carcinogenesis, i.e., after the cancer causing dose of UV had been
      delivered. Perhaps more important, switching from a high-fat to a low-fat diet
      immediately after delivery of the UV-initiating dose negated the exacerbating
      effect of high fat intake. The latter finding suggested that dietary
      modification, even after a cancer-causing exposure to UV, might represent a
      potentially important intervention strategy in the prevention of non-melanoma
      skin cancer (NMSC) and provided the rationale for undertaking a dietary
      intervention trial. One hundred and fifteen skin cancer patients completed the 2
      year clinical trial on the effect of a low-fat diet on occurrence of actinic
      keratosis (AK) and NMSC. Patients were randomly assigned to either continue their
      usual diet (control group, NI) or to adopt a diet with 20% of total caloric
      intake as fat (diet intervention group, DI). All patients were examined at 4
      month intervals for new AK and NMSC. At baseline, the mean percent of caloric
      intake as fat was 40+/-4% in the NI group and 39+/-3% in the DI group. After 4
      months of dietary therapy, the percent calories as fat had decreased to 21+/-7%
      in the DI group. The percent of calories as fat in the NI group did not drop
      below 37% during the study period. The cumulative number of new AK per patient
      from months 4 through 24 was 11.6+/-17 in the NI group and 3.2+/-6 in the DI
      group (P < 0.001). Numbers of new NMSC were analyzed in 8-month periods. There
      were no significant changes in NMSC occurrence in the NI group. However, NMSC
      occurrence in the DI group declined significantly (P < 0.02) in the last 8-month
      period. Patients in the DI group also had significantly (P < 0.01) fewer NMSC in
      the last 8-month period than did patients in the NI group (0.02 versus 0.26).
      Practical dietary advice, with respect to reduction of percent of calories as
      fat, could make an important contribution to the prevention and management of AK
      and NMSC.

PMID- 9920445
TI  - Protection by black tea and green tea against UVB and UVA + B induced skin cancer
      in hairless mice.
AB  - The effects of green and black tea consumption on the early indices of UVB and
      UVA + B skin damage in hairless mice have been studied in the absence of any
      chemical tumour initiators or promoters. Black tea consumption was associated
      with a reduction in the number of sunburn cells in the epidermis of mice 24 h
      after UVA + B irradiation, although there was no effect of green tea. Other
      indices of early damage such as necrotic cells or mitotic figures were not
      affected. Neutrophil infiltration as a measure of skin redness was slightly
      lowered by tea consumption in the UVB group. Consumption of either green or black
      tea resulted in significantly fewer skin papillomas and tumours induced by UVA +
      B light, however black tea provided better protection against UVB-induced tumours
      than green tea. This study confirms earlier reports that tea consumption can
      reduce the incidence of skin cancer in hairless mice, and indicates that black
      tea may afford more protection against simulated solar irradiation than green
      tea.

PMID- 9920446
TI  - Melanocortin mediated inhibition of feeding behavior in rats.
AB  - Melanocortinergic neurons are believed to play a role in the control of food
      intake. Melanocortin receptor agonists and antagonists modulate feeding in
      several mouse models of chemically and genetically induced hyperphagia. To date,
      little information is available describing the role of this neurological system
      in the control of the natural feeding cycle in genetically intact rats. To
      evaluate the involvement of melanocortins in spontaneous nocturnal feeding, the
      synthetic melanocortin receptor agonist, MTII and the antagonist, SHU9119 were
      administered ICV (third ventricle) alone and in combination. Dose-dependent
      inhibition or stimulation of food intake was observed with MTII or SHU9119,
      respectively. Co-injections containing equal concentrations of MTII and SHU9119
      resulted in food intake that was indistinguishable from controls. Food intake
      patterns observed in studies in which various dose combinations of MTII and
      SHU9119 were co-injected are consistent with the concept that both affect feeding
      by acting on similar melanocortin receptors. The hypothesis that effects of
      melanocortins on feeding may be mediated via an NPY related pathway was tested by
      co-injecting MTII and NPY in a 2-h satiated food intake paradigm. MTII inhibited
      food intake induced by 5.0 microg hNPY in a dose dependent manner with the
      highest dose tested abolishing the NPY feeding response. The studies suggest that
      melanocortins act via specific receptors to control food intake in rats, possibly
      via an NPY related pathway. If similar neurochemical processes operate in humans,
      selectively modulating specific melanocortin receptor signaling may be an
      approach to the treatment of human obesity.

PMID- 9920447
TI  - Brain natriuretic peptide enhances the endothelium-independent cAMP and
      vasorelaxant responses of calcitonin gene-related peptide in rat aorta.
AB  - Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta
      involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and
      cGMP levels. When endothelium is removed, preincubation with exogenous NO
      uncovers and potentiates direct (endothelium-independent) cAMP elevations and
      vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves
      elevation of cGMP and inhibition of Type III (cGMP-inhibitable)
      phosphodiesterase, causing accumulation of cAMP. However, NO may have other
      actions. The aim of the present study was to determine if brain natriuretic
      peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP
      accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of
      endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered
      cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM)
      significantly elevated cAMP levels (from control of 0.95+/-0.08 to 1.53+/-0.09
      pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and
      this response was not altered by co-administration of CGRP (100 nM). Pretreatment
      with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings
      greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control
      of 0% to 57.6+/-6.8% relaxation of phenylephrine-precontractions). Our findings
      indicate that BNP enhances direct (endothelium-independent) cAMP elevations and
      vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that
      cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic
      smooth muscle cells.

PMID- 9920448
TI  - Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin
      II in rat spinal cord: a search for selectivity of delta receptor subtypes.
AB  - Deltorphins show a high affinity and selectivity for delta opioid receptors.
      Analogs of deltorphins with substitution of Val residues with more hydrophobic
      Ile appear to have a higher in vitro activity and selectivity than parent
      deltorphins. In our study, changes in the nociceptive threshold after
      intrathecally injected deltorphin I (DELT I), deltorphin II (DELT II) and their
      Ile - derivatives (ILE-DELT I and ILE-DELT II, respectively) were investigated in
      a tail-flick (TF) and a paw pressure (PP) tests. Male Wistars rats (260-350 g)
      with a chronically implanted catheter in the lumbar enlargement of the spinal
      cord were used. DELT I and DELT II, injected i.th. in doses of 0.15, 1.5 and 15
      microg, increased the TF latency in a dose-dependent manner. The effect of their
      derivatives was similar, but the action of ILE-DELT II was shorter than that of
      the parent peptide. In the PP test, the antinociceptive effects of DELT I and
      their derivative ILE-DELT I were similar, but the effect of a higher dose of ILE
      DELT I lasted longer in comparison with the parent peptide. Both DELT II and ILE
      DELT II exhibited a low and short-lasting antinociceptive potency in the PP test.
      The effect of DELT I (1.5 microg) was antagonized by pretreatment with NTI (30
      microg), a non-selective delta opioid receptor antagonist, as well as by the
      delta2 receptor antagonist NTB (3 microg) and the delta1 antagonist BNTX (1
      microg) in both those tests used. The antinociceptive effect of DELT II (1.5
      microg) was antagonized by pretreatment with NTI (30 microg) and NTB (3 microg)
      in the TF test, but not in the PP test. In the latter test, the antinociceptive
      effect of DELT II was potentiated by pretreatment with BNTX (1 microg). The
      effects of both the derivatives ILE-DELT I and ILE-DELT II were antagonized by
      NTI (30 microg) in the TF test, and by NTI (30 microg) and NTB (3 microg) in the
      PP test. Like in the case of the parent peptide, the effect of ILE-DELT II was
      potentiated by pretreatment with the delta1 antagonist BNTX (1 microg). Summing
      up, modification of the DELT I and II by substituting Ile for Val residues
      appears to influence the delta selectivity rather then the potency of the
      peptides at spinal delta receptors.

PMID- 9920449
TI  - Substance P fragments and striatal endogenous dopamine outflow: interaction with
      substance P.
AB  - Accumulating evidence shows that N- and C-terminal substance P fragments have
      significant biological activity. Substance P(1-9) and substance P(6-11) have been
      reported to be major substance P metabolites in rat striatum. We investigated the
      effects of these fragments on endogenous dopamine outflow in rat striatal slices.
      Substance P-(1-9) and substance P-(6-11) induced a significant increase in
      dopamine outflow at 0.1 and 1 nM. The effects of substance P-(6-11) (1 nM) were
      reversed by the tachykinin NK1 antagonist WIN 51,708 (17beta-hydroxy-17alpha
      ethynyl-5alpha-androstano[3,2- b]pyrimido[1,2-a]benzimidazole) (2.5 nM), whereas
      the effects of substance P-(1-9) were not modified by the antagonist. Substance P
      (1-9) and substance P-(6-11) (1 nM) did not increase the dopamine overflow
      induced by 25 mM KCI. The effects of the two fragments were reversed by the
      muscarinic antagonist atropine (1 microM) but not by nicotinic antagonists
      dihydro-beta-erythroidine (0.5 microM) and pempidine (10 microM). The co
      incubation of tissue with substance P and each fragment in a 1/1 or 10/1 ratio of
      substance P to metabolite revealed a negative interaction between parent and
      fragments. A similar pattern was observed when substance P was co-administered
      with the active fragments substance P(1-4), substance P(1-7), substance P(5-11)
      and substance P(8-11). The data show that substance P-(1-9) and substance P-(6
      11) have modulatory effects similar to substance P. However, the presence of
      active substance P metabolites does not appear to amplify the signal mediated by
      the parent peptide.

PMID- 9920450
TI  - Changes in pituitary adenylate cyclase activating peptide and vasoactive
      intestinal peptide innervation of rat oxyntic mucosa during ulcer healing.
AB  - Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide
      belong to the same neuropeptide family. Both peptides are present in nerve fibers
      in the gastric wall and are thought to be involved in the regulation of
      inflammatory processes. Experimental ulcers were induced in the rat gastric
      mucosa by local application of acetic acid. During the healing process we
      examined the PACAP and VIP innervation by means of immunohistochemistry and in
      situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer
      induction. There was a marked depletion of PACAP in nerve fibers at the ulcer
      margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve
      fibers could again be visualized at the ulcer margin. In contrast, VIP
      immunoreactive nerve fibers were present at the ulcer margin at all time points
      studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive
      nerve fibers were increased in frequency in the smooth muscle beneath the ulcer.
      An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric
      ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and
      VIP react differently to the inflammation at the ulcer margin but similarly in
      the smooth muscle during the ulcer healing.

PMID- 9920451
TI  - Effects of a tachykinin NK3 receptor antagonist, SR 142801, studied in isolated
      neonatal rat spinal cord.
AB  - Effects of a nonpeptide tachykinin NK3 receptor antagonist, SR 142801, were
      studied in the isolated spinal cord preparation of the neonatal rat. Potential
      changes were recorded extracellularly from a lumbar ventral root. Bath
      application of neurokinin B induced a dose-dependent depolarization of the
      ventral root. SR 142801 caused rightward shifts of the concentration-response
      curve for neurokinin B with pA2 of 6.57, but did not affect the depolarizing
      responses to other agonists. Stimulation of a dorsal root evoked in the
      ipsilateral ventral root of the same segment monosynaptic and polysynaptic
      reflexes of fast time course which were followed by a slow depolarization
      (ipsilateral slow ventral root potential). SR 142801 depressed the ipsilateral
      slow ventral root potential. The present results indicate that SR 142801 is a
      specific antagonist for tachykinin NK3 receptors in the spinal cord and suggest
      that NK3 receptors are involved in primary afferent-evoked nociceptive responses
      of spinal neurones.

PMID- 9920452
TI  - Sensory stimulation (acupuncture) increases the release of vasoactive intestinal
      polypeptide in the saliva of xerostomia sufferers.
AB  - We have shown in earlier studies that xerostomia can be treated successfully with
      acupuncture. We also found that acupuncture stimulation can increase the
      concentration of neuropeptides in the saliva of healthy subjects. In this study,
      the concentration of the neuropeptide vasoactive intestinal polypeptide (VIP) was
      measured in the saliva of xerostomic patients in connection with acupuncture
      treatment (AP). Patients suffering from xerostomia caused by irradiation
      treatment, Sjogren's syndrome and other systemic disorders had been treated with
      acupuncture. Some of these patients showed an increase of their salivary flow
      rates after the AP was completed. Seventeen patients out of 65 were chosen due to
      their ability to produce enough saliva for the radio immunoassay (RIA) analyses
      to be conducted prior to the start of AP. VIP-like immunoreactivity (VIP-LI) was
      measured in the chewing stimulated saliva of these patients before and after the
      whole AP (24 sessions of 30 min each). The results showed that there was a
      significant increase of the concentration of VIP after the AP as compared to the
      measurements made before the start of the treatment (p<0.05). We concluded that
      the increase of neuropeptide VIP might be one of the mechanisms behind the
      positive effect of acupuncture on the salivary flow rates of the xerostomic
      patients.

PMID- 9920453
TI  - Changes with age in the modulation of natural killer activity of murine
      leukocytes by gastrin-releasing peptide, neuropeptide Y and sulfated
      cholecystokinin octapeptide.
AB  - Several investigations have suggested that the interactions between the nervous
      and immune systems are modified with age. The aim of the present work was to
      study the effect of three neuropeptides: gastrin-releasing peptide (GRP),
      neuropeptide Y (NPY) and sulfated cholecystokinin octapeptide (CCK-8 s) on
      natural killer (NK) activity of spleen, thymus and axillary node leukocytes from
      BALB/c male, young (8+/-1 weeks), adult (24+/-2 weeks) and old (72+/-2 weeks)
      mice. We used cells from murine lymphoma YAC-1 as targets for the cytotoxic assay
      and three physiological concentrations of the neuropeptides (10(-8), 10(-10) and
      10(-12) M). In control samples, in the absence of neuropeptide, we observed a
      decreased NK activity in young and old mice with respect to the adults in the
      three organs studied. Regarding the effect of the neuropeptides, GRP stimulates
      the cytotoxic activity of leukocytes from all locations, in adult animals. At the
      same age, NPY also stimulates the NK activity of leukocytes from axillary nodes
      and thymus, whereas it decreases the NK activity of spleen leukocytes from young
      mice. CCK-8 s has an inhibitory effect on the axillary node leukocytes from young
      mice and spleen leukocytes from old animals. However, CCK-8 s increased the NK
      activity of thymus leukocytes from young and adult mice. The results indicate
      that the highest values of NK activity are found in adult mice, and that the
      stimulating effect of the three neuropeptides studied on NK activity of
      leukocytes from adult mice are reduced or disappeared, in general, in old as well
      as in young animals. Furthermore, the changes observed with ageing in the
      modulation of NK activity by the neuropeptides studied suggest an altered
      integration of the nervous and immune systems.

PMID- 9920455
TI  - Effect of nitric oxide on basal and TRH-or metoclopramide-stimulated prolactin
      release in normal men. volpi@ipruniv.cce.unipr.it.
AB  - In order to establish whether nitric oxide (NO) is involved in the regulation of
      basal and/or TRH- or metoclopramide (MCP)-stimulated PRL secretion, normal male
      subjects were treated i.v. with the NO-synthase (NOS) inhibitor N-nitro-L
      arginine methyl ester (L-NAME) (40 mg/kg injected plus 50 mg/kg infused over 60
      min) in basal conditions (N.7 subjects) or just before the PRL releasing hormone
      TRH (20 or 200 microg iv) (N.7 subjects) or the antidopaminergic agent MCP (1 or
      10 mg iv) (N.7 subjects). In control experiments, subjects received normal saline
      instead of L-NAME. The administration of L-NAME modified neither the basal
      secretion of PRL, nor the PRL release induced by TRH (20 or 200 microg) or MCP (1
      or 10 mg). These data suggest that in humans, NO is not involved in the control
      of PRL release at the anterior pituitary level.

PMID- 9920454
TI  - Vasoactive intestinal polypeptide induces analgesia and impairs the
      antinociceptive effect of morphine in mice.
AB  - Vasoactive intestinal polypeptide (VIP) has numerous regulatory roles in
      peripheral, endocrine organs and in the central nervous system. The present study
      related to the effects of centrally (intracerebroventricularly) administered VIP
      on pain sensitivity and on opiate tolerance and dependence in intact male CFLP
      mice. VIP was analgesic when administered alone centrally. Naloxone treatment
      abolished this analgesic effect. VIP decreased the analgesic effect of a single
      subcutaneous morphine injection and the development of chronic tolerance to
      morphine. Morphine withdrawal signs were not significantly affected after VIP
      pretreatment. These findings indicate that VIP may play a role in pain
      sensitivity and that an opiate component may participate in this effect.

PMID- 9920456
TI  - Orphanin FQ/nociceptin modulates glutamate- and kainic acid-induced currents in
      acutely isolated rat spinal dorsal horn neurons.
AB  - The heptadecapeptide orphanin FQ (OFQ), also known as nociceptin (NOC), is a
      newly discovered endogenous ligand for the opioid-like G-protein coupled
      receptor, ORL1. In the present study, the effects of OFQ/NOC on glutamate (Glu),
      kainic acid (KA) and quisqualic acid (QA) induced currents were examined in
      isolated rat spinal dorsal horn neurons of young rats using whole-cell patch
      clamp techniques. Glu, KA and QA elicited rapid inward currents in 90%, 69%, 83%
      of tested neurons. OFQ/NOC(0.03 approximately 300 nM) failed to induce any
      changes of membrane currents, but modulated Glu-, KA- and QA-elicited currents.
      OFQ/NOC inhibited and potentiated Glu-induced currents in 40.6% and 27.3% of
      examined cells (n=106) respectively. In about one third examined neurons, OFQ/NOC
      had no detectable effects on Glu responses. OFQ/NOC also inhibited and enhanced
      KA- and QA-induced currents (inhibition: KA, 67.1%, n=76; QA, 50%, n=36.
      Potentiation: KA, 23.7%, n=76; QA, 16.7%, n=36). In about 10% of tested cells,
      Glu-induced currents were potentiated after the application of OFQ/NOC, and
      lasted for 20 approximately 30 min. The inhibitory effects of OFQ/NOC on KA and
      QA responses were naloxone-insensitive. The C-terminal fragment OFQ(8-17)
      presented same effects on EAA-induced responses. Taken together, OFQ/NOC
      primarily inhibited Glu-, KA- and QA-induced currents in isolated rat spinal
      dorsal horn neurons via non-opioid mechanism, which might contribute to
      nociceptive transmission in the spinal level.

PMID- 9920457
TI  - Evaluation of behavioural effects of neural melanocortin receptor antagonists
      injected ICV and in VTA in rats.
AB  - The natural melanocortic peptides are known to exert a variety of effects after
      central administration. Recently, we discovered the first potent and selective
      substances for the MC4 receptor, i.e. HS964 and HS014. We found HS964 to be an
      antagonist for the MC1, MC3, MC4 and MC5 receptors in vitro. HS014 is an
      antagonist for the MC3 and MC4 receptors and a partial antagonist for the MC1 and
      MC5 receptors. We injected alpha-MSH and these substances, both
      intracerebroventricular (ICV) and in the ventral tegmental area (VTA) in rats and
      scored several behavioural effects. The results show that alpha-MSH caused
      intensive grooming which was antagonized by pre-treatment of both HS014 and
      HS964. The data give further support to the hypothesis that it is the MC4
      receptor which mediates grooming in rodents. The grooming effects of alpha-MSH
      were more pronounced after intra-VTA administration compared to the ICV
      administration. Both alpha-MSH, HS014 and HS964 caused an increase in vertical
      activity of the rats after intra-VTA administration but not after ICV
      administration. Horizontal activity was virtually not affected by the
      administration of the peptides. The data indicate that the neural MC3 and MC4
      receptors are not likely to be an important mediators of locomotor activity in
      rats.

PMID- 9920458
TI  - Cerebrospinal fluid somatostatin in West syndrome: changes in response to
      combined treatment with high-dose pyridoxal phosphate and low-dose corticotropin.
AB  - Eighteen children with West syndrome (5-11 months of age) were selected to
      receive an oral dose of pyridoxal phosphate, (20-50 mg/kg) for 14 d. Seizures
      disappeared in one patient. The remaining 17 patients were treated with 0.01
      mg/kg synthesized corticotropin intramuscularly for 2 weeks as an additional
      therapy. Seizures disappeared in all 17 patients within a few days after
      initiation of the corticotropin. Levels of somatostatin in the cerebrospinal
      fluid were as follows: 61.0+/-10.7 pg/ml before therapy, 34.2+/-6.4 pg/ml during
      pyridoxal phosphate therapy, and 26.8+/-4.2 pg/ml after 2 weeks corticotropin
      therapy. Somatostatin levels in untreated patients were higher (p < 0.05) than
      those of age-matched controls (35.7+/-11.8 pg/ml) and decreased (p < 0.05) after
      pyridoxal phosphate treatment. Somatostatin is a hypothalamic tetradecapeptide
      with excitatory effects on neurons and pyridoxal phosphate might subclinically
      influence neuronal excitation.

PMID- 9920459
TI  - The small G-proteins Rap 1 as potential targets of vasoactive intestinal peptide
      effects in the human clonic cancer cells HT29.
AB  - We recently reported that the vasoactive intestinal peptide (VIP) potently
      inhibited proliferation and induced in parallel a strong cAMP rise, in the human
      colonic cancer cell line HT29. In this study, we investigated whether Rap 1
      proteins could be potential targets of VIP effects in HT29 cells. These Ras
      related proteins in which activity was demonstrated to be regulated by PKA
      phosphorylation, are considered as potential modulators of the Ras / Raf / MAP
      kinases cascade that governs cell growth control. Our data revealed that the Rap
      1a isoform is highly expressed in HT29 cells and mainly localized in a late
      endosomal compartment. In these cells, VIP induces Rap 1 phosphorylation and a
      yet unidentified modification that leads to their acidification. This latter Rap
      1 acidification seems to be, at least partially, cAMP-dependent. It is concluded
      that in HT29 cells, Rap 1 proteins may be part of a VIP-induced signaling
      cascade.

PMID- 9920460
TI  - Quantitative structure-activity relationships (QSAR) for 9-anilinoacridines: a
      comparative analysis.
AB  - A new analysis of the quantitative structure-activity relationship (QSAR) of the
      antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse
      toxicity is reported. QSAR have also been derived for the inhibitory activity of
      the anilinoacridines with tumor cells and their binding to DNA. These results are
      compared with reactivity with simple nucleophiles. The comparative analysis shows
      the importance of electron releasing substituents (in general negative
      coefficients with the Hammett parameter sigma+) throughout the various systems
      and the complete lack of hydrophobic interactions from DNA to cells to mice. The
      presence of steric terms suggests that a protein receptor is involved. The study
      shows that QSAR has an important role to play in improving the efficiency in the
      design of bioactive compounds and that care must be taken in the design of a set
      of congeners so that the necessary parameters are available to do the QSAR
      analysis. Our study illustrates the value of comparative QSAR in generalizing our
      understanding of chemical-biological interactions.

PMID- 9920461
TI  - In vitro biotransformation of atrazine by rat liver microsomal cytochrome P450
      enzymes.
AB  - We studied atrazine (ATZ) metabolism in male and female rat liver microsomes in
      vitro, and the major metabolite was deisopropylatrazine (DeiPr-ATZ) with
      deethylatrazine (DeEt-ATZ) and 1-hydroxyisopropylatrazine (iPrOH-ATZ) as minor
      metabolites in both sexes. The enzyme kinetics of ATZ biotransformation were
      examined by means of Eadie-Hofstee analyses. Although no remarkable sex
      difference of Michaelis Menten values for each pathway was observed, Cl(int)S
      (Vmax/Km) for DeiPr-ATZ, DeEt-ATZ and iPrOH-ATZ were slightly higher in female
      than in male rats. The formation of DeiPr-ATZ, DeEt-ATZ and iPrOH-ATZ from ATZ
      was substantially inhibited by SKF-525A, metyrapone, diallyl sulfide, 7
      ethoxycoumarin, benzphetamine, nicotine, testosterone and lauric acid in both
      sexes. Cimetidine effectively inhibited the formation of all metabolites in male
      rats. On the other hand, the inhibition rates of the formation of DeiPr-ATZ and
      iPrOH-ATZ by cimetidine in female rats were lower than those in male rats, and
      DeEt-ATZ was hardly affected by the chemicals. In contrast with the results for
      cimetidine, the inhibition of ATZ biotransformation by bufuralol was more
      effective in female than in male rats. Anti-rat CYP2B1 and CYP2E1 antibodies
      effectively inhibited DeiPr-ATZ, DeEt-ATZ and iPrOH-ATZ formations in both sexes.
      Anti-rat CYP2C11 antibody also inhibited the three metabolites in both sexes,
      with the inhibition rates higher in male than in female rats, similar to
      cimetidine. In the case of anti-rat CYP2D1 antibody, the inhibitory effect on ATZ
      biotransformation in male rats was less than that in female rats. On the other
      hand, anti-rat CYP1A2, CYP3A2 and CYP4A1 antibodies did not affect the ATZ
      biotransformation in either sex. There was no significant correlation between the
      formation rate of ATZ metabolites and P450 isoform levels in either sex. These
      results may mean that CYP2B2, CYP2C11, CYP2D1 (only iPrOH-ATZ formation) and
      CYP2E1 in male rats, and CYP2B2, CYP2D1 and CYP2E1 in female rats are involved
      ATZ metabolism in liver, and that the substrate specificity of P450 isoforms for
      ATZ is broad.

PMID- 9920462
TI  - Benzo[a]pyrene diol-epoxide DNA adducts and levels of polycyclic aromatic
      hydrocarbons in autoptic samples from human lungs.
AB  - Benzo[a]pyrene (BaP) and other polycyclic aromatic hydrocarbons (PAHs) which are
      present in cigarette smoke, are common air and food genotoxic contaminants and
      possible human carcinogens. We measured the following PAH levels:
      benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, BaP,
      dibenzo[a,h]anthracene, benzo[g,h,i]perylene as well as (+/-) syn and anti BaP
      diol-epoxide (BPDE) DNA adducts in autopsy samples from the lungs of non-smokers,
      ex-smokers and smokers who had lived in Florence, Italy. PAH levels in lung
      tissue were similar in all groups, with the exception of dibenzo[a,h]anthracene
      (DBA), which was higher in lung samples from smokers (n = 10, 0.18+/-0.17 ng/g
      d.w, mean +/- S.D.) compared to non-smokers (n = 15, 0.046+/-0.025 ng/g d.w) (P <
      0.05), whereas ex-smokers (n = 5), had intermediate levels (0.07+/-0.03 ng/g
      d.w). The average level of total BPDE-DNA adducts was 4.46+/-5.76 per 10(8) bases
      in smokers, 4.04+/-2.37 per 10(8) in ex-smokers and 1.76+/-1.69 per 10(8) in non
      smokers. The levels of non-smokers were significantly different (P < 0.05) from
      the levels of the smokers and ex-smokers combined. Total BPDE-DNA adducts were
      correlated with BaP levels in the lung samples in which both determinations were
      obtained (r = 0.63). Our results demonstrate that the biological load of PAHs due
      to environmental pollution is similar in individuals who smoke and those who do
      not, but BPDE-DNA adducts are higher in smokers and ex-smokers compared to non
      smokers. This study further confirms the usefulness of BPDE-DNA adduct levels
      determination in the lungs from autopsy samples for monitoring long-term human
      exposure to BaP, a representative PAH.

PMID- 9920463
TI  - The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth
      and enzyme activities of MCF7 human breast cancer cells.
AB  - Humans ingest about 1 g of flavonoids daily in their diet, and they are
      increasingly being associated with cytoprotective antitumour properties. The
      mechanism(s) responsible for these effects have not yet been elucidated but may
      involve interaction with xenobiotic metabolising enzymes to alter the metabolic
      activation of potential carcinogens. We have investigated the effect of the
      flavonoids, quercetin (Q), myricetin (M) and epicatechin (E) on the growth,
      morphology and enzyme activities of MCF7 human breast cancer cells. Of the three
      flavonoids studied only Q caused a decrease in cell protein content and decreased
      the reduction of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium). It
      also inhibited protein, DNA and RNA synthesis to the greatest extent. Q and M
      increased intracellular reduced glutathione (GSH) content, and Q altered the
      morphology of the cells after 24 h exposure to 25 microM. E and Q inhibited the O
      deethylation of ethoxyresorufin (EROD) catalysed by cytochrome P450 CYPIA. In
      contrast, M increased the EROD reaction 2-fold. Q increased the activity of DT
      diaphorase, NADPH cytochrome c reductase and glutathione reductase, while E
      increased only NADPH cytochrome c reductase activity. The effects on enzyme
      activities in vitro suggest that there is not only the potential for flavonoids
      to alter metabolic activation of carcinogens but also of therapeutically
      administered drugs in vivo. We are at present investigating the synergy between
      anti-cancer drugs and flavonoids in terms of anti-tumour efficacy.

PMID- 9920464
TI  - Differential induction of rat hepatic microsomal epoxide hydrolase and rGSTA2 by
      diazines: the role of cytochrome P450 2E1-mediated metabolic activation.
AB  - Previous studies have shown that pyridazine (PD) and pyrazine (PZ) are
      efficacious in inducing microsomal epoxide hydrolase (mEH) in the liver with
      elevation of the mRNA level. The present study was designed to investigate the
      expression of mEH and rGSTA2 genes in response to the diazines including PD, PZ
      and pyrimidine (PM) and the basis for their enzyme induction. Rats treated with
      either PD or PZ for 3 days resulted in marked increases in mEH and rGSTA2 mRNA
      levels with concomitant induction of the proteins, whereas PM failed to elevate
      the mRNA levels. Treatment of rats with a single dose of PD or PZ showed dose
      dependent increases in mEH and rGSTA2 mRNA levels at 24 h with ED50 values being
      approximately 10 mg/kg. Time-course studies showed that the mRNA levels were
      increased to maximal extents at 24-48 h after treatment. Studies were extended to
      assess the mechanistic basis for the enzyme induction by PD and PZ. beta
      Naphthoflavone (BNF) caused a 6-fold increase of rGSTA2 mRNA in the liver (100
      mg/kg per day, p.o., 3 days), as compared to control, whereas the agent failed to
      increase mEH mRNA level. Administration of PD or PZ (50 mg/kg) to BNF-pretreated
      rats resulted in no enhanced increase of the mEH mRNA as compared to the
      individual treatment, while the rGSTA2 mRNA level was additively elevated,
      suggesting the possibility that increases of the mEH and rGSTA2 mRNAs by PD or PZ
      might be mediated with antioxidant responsive element(s) in the genes, but not
      with xenobiotic responsive element. Western blot analysis revealed that
      cytochrome P450 2E1 was induced 3- to 4-fold by both PD and PZ, whereas PM failed
      to induce P450 2E1. Concomitant treatment of rats with PD or PZ in combination
      with acetone, a substrate for P450 2E1, caused no significant increase in the mEH
      and rGSTA2 mRNA levels relative to that in untreated animals, whereas PD or PZ
      treatment without a concomitant acetone administration resulted in marked
      increases of the mRNAs. Diazine-inducible mEH and rGSTA2 mRNA levels were
      approximately 2-fold enhanced in P450 2E1-induced starved rats, as compared to
      those in diazine-treated unstarved animals. These data indicate that P450 2E1
      mediated bioactivation of the diazines might contribute to transcriptional
      activation of the mEH and GST genes. These results provide evidence that both PD
      and PZ efficaciously induce mEH and rGSTA2 in the liver with increases in the
      mRNA levels, while PM is ineffective, and that induction of mEH and rGSTA2 may be
      mediated through bioactivation of the diazines by P450 2E1.

PMID- 9920465
TI  - No abrupt change in visual hemineglect from near to far space.
AB  - In thirteen patients with prominent visuospatial hemineglect following acute
      right hemisphere cerebrovascular accident (CVA) and in two normal controls we
      investigated bisection of horizontal lines at various viewing distances. Their
      task was to indicate the centre of each horizontal line using a hand-held laser
      pointer. In five of the thirteen patients the angular error was greater for lines
      further away than for lines of identical angular size within reaching distance,
      confirming previous results [Cowey, A., Small, M., Ellis, S., Visuospatial
      neglect can be worse in far than in near space. Neuropsychologia, 1994, 32, 1059
      1066]. There was no evidence that a sudden increase in the angular displacement
      occurred when the maximum reaching distance was exceeded.

PMID- 9920466
TI  - Is space representation distorted in neglect?
AB  - It has been argued that neglect of contralateral stimuli following brain damage
      might be associated with either a compressed or an anisometric neural
      representation of space along the earth-horizontal axis. Two different models
      have been put forward. One model proposes a uniform compression of subjective
      space, while the other envisages an expansion on one side of space and a
      compression on the other. We tested these models by determining neglect patients'
      perception of spatial distances in the horizontal plane. The models differ
      concerning the expected degree of under- vs overestimation of distances in the
      left and right hemispace. In the first experiment, patients were asked to
      position ten red LEDs equidistantly along a semicircle, which was located
      horizontally in front of them at eye level. A second experiment compared the
      patients' subjective perception of short, medium and long distances extending
      into left and right hemispace. We found no evidence for any compression or
      expansion, nor for anisometry along the earth-horizontal axis. These findings
      argue against a distortion of subjective space along the horizontal axis in
      patients with neglect which could account for their failure to orient towards and
      to explore the contralesional parts of space.

PMID- 9920467
TI  - History of the International Neuropsychological Symposium: a reflection of the
      evolution of a discipline.
AB  - The International Neuropsychological Symposium is the name of a group which,
      since 1951, meets every year for the purpose of promoting knowledge and
      understanding of brain functions and cognate issues on the borderland of
      neurology, psychology and psychiatry. This paper summarizes the history of the
      International Neuropsychological Symposium and is intended as a tribute to Henry
      Hecaen, co-founder and major advocate of the group throughout his entire
      scientific life. It is felt that the evolution of the Symposium may be considered
      a reflection of the evolution of the discipline of Neuropsychology and may help
      to understand the evolution of the field in the past fifty years.

PMID- 9920468
TI  - Retrograde amnesia: clinical and methodological caveats.
AB  - Several clinical and methodological caveats are outlined as they pertain to
      retrograde amnesia research, and data relevant to these caveats are presented.
      Three caveats in particular are noted in relation to recently published cases of
      marked retrograde amnesia; (i) temporal lobe epilepsy may influence memory for
      news events; (ii) there may be additional, unsuspected pathology in cases of
      amnesia, such as those with cerebral hypoxia; (iii) degree of media exposure is
      closely related to performance on the types of news events memory tests that are
      commonly used in retrograde amnesia research.

PMID- 9920469
TI  - Hemispheric asymmetries in global/local processing are modulated by perceptual
      salience.
AB  - It has been claimed that a left hemisphere bias toward local and right hemisphere
      bias toward global visual processing can be explained in terms of specialization
      for relatively high and low spatial frequencies, respectively. Using non
      representational figures, we tested this hypothesis in experiment 1 using
      positron emission tomography (PET) measures of cerebral activity in 10 normal
      volunteers. In each block of trials subjects viewed either a relatively high or a
      relatively low spatial frequency grating. The orientation (vertical or
      horizontal) of the grating changed from trial to trial. In a directed attention
      task, subjects reported the orientation of either the whole stimulus (globally
      directed attention) or the orientation of the component parts thereof (locally
      directed attention). A significant interaction between hierarchical processing
      level (global or local) and stimulus level (relatively high or relatively low
      spatial frequency within the absolute low spatial frequency range) was found.
      Globally directed attention led to significantly increased cerebral activity in
      the right hemisphere when relatively high spatial frequency stimuli were used but
      not when relatively low spatial frequency stimuli were used. Likewise, locally
      directed attention increased cerebral activity when low but not high spatial
      frequency stimuli were used. On the basis of these results we suggest that
      perceptual salience of the global or local form modulates hemispheric processing
      asymmetries in early visual cortex. In experiment 2, the perceptual salience of
      global form in relatively high spatial frequency stimuli and of local form in
      relatively low spatial frequency stimuli was confirmed in a reaction time (RT)
      study. In combination, the results of the two experiments suggest that perceptual
      salience takes precedence over spatial frequency (within the range studied here)
      in determining the cerebral organization of global/local processing.

PMID- 9920470
TI  - Impaired face and word recognition without object agnosia.
AB  - A leading account of high-level visual recognition proposes that the recognition
      of faces, objects, and words is mediated by two processing capacities. Words are
      assumed to require the capacity to represent numerous parts, whereas faces are
      processed wholistically. and hence require the representation of complex units.
      Object recognition requires the capacity to represent both numerous and complex
      parts. As object recognition depends upon the same processing capacities
      underlying face and word recognition, this account predicts that patients with
      severe alexia and prosopagnosia should be deficient in tests of object
      recognition. We report a patient who is unable to recognize words or faces, yet
      performs relatively well on tests of object recognition. The two-capacity theory
      cannot accommodate this pattern of performance without additional assumptions.

PMID- 9920471
TI  - Naturalistic action production following right hemisphere stroke.
AB  - An unselected group of right hemisphere, semi-acute stroke patients (n = 30) was
      run on a laboratory test of naturalistic action production and was found to
      commit errors of action at a higher rate than what was previously reported for
      recovering head injury patients [Schwartz et al., Naturalistic action impairment
      in closed head injury. Neuropsychology, 1997, 8, 59-72]. There were strong
      similarities in how these two patient groups responded to variations in task
      demands and in the pattern of errors they produced. Hemispatial biases were
      evident in the errors of right hemisphere patients with neglect but not those
      without neglect; and neglect patients also many errors that were unrelated to the
      spatial layout. We argue that a non-specific resource limitation--which might
      translate as reduced arousal or effort--is central to the breakdown of
      naturalistic action production after brain damage, and right hemisphere patients
      are especially vulnerable to this resource limitation and its behavioral
      consequences.

PMID- 9920472
TI  - Category specificity in object agnosia: preservation of sensorimotor experiences
      related to objects.
AB  - We report a case of semantic agnosia, characterized by category specificity.
      Object recognition, mainly involving visual representation, was severely
      impaired, whereas object recognition involving both visual and sensorimotor
      representations, was relatively well preserved. His ability to recognize gestures
      and produce appropriate gestural responses to objects was remarkable. These two
      factors lead the authors to form a hypothesis, in an attempt to explain the
      mechanisms involved in object recognition. It has been argued that manipulation
      of an object may give access to a certain amount of knowledge about it, and that
      preservation of sensorimotor experiences of objects might be important in
      recognizing some of them. This could account for the category specificity,
      described in object agnosia.

PMID- 9920473
TI  - Unassociated responses to two related task demands: a negative factor for
      improvement of unilateral spatial neglect.
AB  - Patients with relatively mild unilateral spatial neglect underwent the line
      bisection task with self-estimation, where they were asked two different
      questions about the relationship of their subjective midpoint to the line. For
      the first trial, all patients responded by "yes" when asked whether their
      subjective midpoint was placed at the center of the line, but by "left" or
      "right" when asked to indicate the longer segment of the bisected line. In the
      subsequent trials, they repeatedly reported that their subjective midpoints were
      placed at the true center, even after they had recognized their bisection errors
      when indicating the longer segment. Of the 32 patients, 28 kept on showing this
      pattern of responses in almost all the 30 trials. Moreover, the patients who
      could estimate the longer segment showed no improvement of line bisection
      throughout the trials. Their performances strongly depended upon the task demand
      regarding the subjective midpoint. These results demonstrate that the patients
      treated the two related tasks as independent. Accordingly, they could not improve
      their performances on one task with the feedback from their performances on the
      other. The lack of association between the responses to two related task demands
      may be one of the factors that prevent patients with unilateral spatial neglect
      from improving the deficit.

PMID- 9920474
TI  - At which steps of spatial working memory processing do striatofrontal circuits
      intervene in humans?
AB  - Striatofrontal circuits have been implicated in spatial working memory in non
      human and human primates. To determine at which steps of information processing
      (stimulus encoding, storage or response programming) they intervene, we compared
      32 levodopa-treated patients with idiopathic Parkinson's disease (PD) and 32
      matched control subjects in a visuo-spatial pattern span paradigm. Our testing
      procedure allowed us to evaluate the influence of: (1) the type of encoding
      (controlled vs free); (2) the nature of interference during a 10 s delay (spatial
      vs verbal); and (3) response elaboration (reproduction vs error detection). As
      expected, the performance of control subjects was significantly better in
      controlled than in free encoding, in verbal than in spatial interference and in
      detection than in reproduction, clearly demonstrating the sensitivity of the
      procedure to these factors. Compared to controls, PD patients were impaired in
      all conditions and the severity of the deficit was significantly correlated with
      that observed in tests of executive functions. The global pattern of performance,
      however, was identical to that of controls. These data confirm the involvement of
      striatofrontal circuits in spatial working memory in humans and suggest that the
      executive working memory component intervenes at all steps of working memory
      processing.

PMID- 9920475
TI  - Visual discrimination and attention after bilateral temporal-lobe lesions: a case
      study.
AB  - We studied a woman (Case 1) who acquired achromatopsia, prosopagnosia, and memory
      loss after sustaining bilateral temporal-lobe lesions. Given her symptoms and
      locus of lesion, the affected area may be related to the monkey visual area IT.
      In order to examine her deficits, we assessed her basic discrimination capacities
      in several domains. She performed normally when stimuli differed in contrast,
      size, or motion. her performance was abnormal for patterned targets, and was
      markedly impaired when the patterned targets were less prominent than
      distractors. This impairment decreased with practice. These symptoms partially
      resemble the deficits that have been found in monkeys with lesions in visual
      cortical area V4.

PMID- 9920476
TI  - Neural correlates of semantic and episodic memory retrieval.
AB  - To investigate the functional neuroanatomy associated with retrieving semantic
      and episodic memories, we measured changes in regional cerebral blood flow (rCBF)
      with positron emission tomography (PET) while subjects generated single word
      responses to achromatic line drawings of objects. During separate scans, subjects
      either named each object, retrieved a commonly associated color of each object
      (semantic condition), or recalled a previously studied uncommon color of each
      object (episodic condition). Subjects were also scanned while staring at visual
      noise patterns to provide a low level perceptual baseline. Relative to the low
      level baseline, all three conditions revealed bilateral activations of posterior
      regions of the temporal lobes, cerebellum, and left lateralized activations in
      frontal regions. Retrieving semantic information, as compared to object naming,
      activated left inferior temporal, left superior parietal, and left frontal
      cortices. In addition, small regions of right frontal cortex were activated.
      Retrieving episodic information, as compared to object naming, activated
      bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal
      cortex, thalamus, and cerebellum. Direct comparison of the semantic and episodic
      conditions revealed bilateral activation in temporal and frontal lobes in the
      semantic task (left greater than right), and activation in medial parietal
      cortex, retrosplenial cortex, thalamus, and cerebellum (but not right frontal
      regions) in the episodic task. These results support the assertion that distinct
      neural structures mediate semantic and episodic memory retrieval. However, they
      also raise questions regarding the specific roles of left temporal and right
      frontal cortices during episodic memory retrieval, in particular.

PMID- 9920477
TI  - Structure-function properties of venom components from Australian elapids.
AB  - A comprehensive review of venom components isolated thus far from Australian
      elapids. Illustrated is that a tremendous structural homology exists among the
      components but this homology is not representative of the functional diversity.
      Further, the review illuminates the overlooked species and areas of research.

PMID- 9920478
TI  - Thermal stability studies of hyperimmune horse antivenoms.
AB  - Ampoules of horse antivenoms raised against Bothrops spp and Crotalus durissus
      (final product) produced by Fundacao Ezequiel Dias (FUNED) were fractionated on
      the molecular filtration chromatography (SUPEROSE 12) and the expected MW species
      of F(ab')2 fragments were observed. It has been known that high temperatures
      promote aggregation and formation of protein precipitates. Phenol is used in
      preparations of antivenoms as preservative; however, as thus is a hydrophobic
      substance, it can also induce an increase in protein denaturation. Sorbitol and
      glycerol were used as osmolyte (natural substance or organic compound capable of
      stabilizing proteins) and decreased the formation of protein precipitates in
      solutions of antibodies; as judged by a spectrophotometric assay (280 nm), by
      nephelometry or when tested by the ELISA. In 1.0 M concentration, the sorbitol
      presented the best results when compared with glycerol. Circular Dichroism (CD)
      was used to study the spectra of antibodies in the presence of PBS, glycerol or
      sorbitol. Up to 1.0 M concentration of the osmolyte, there is no significant
      perturbation of the antibodies spectra in the amide region, in control samples
      not incubated (kept at room temperature with no phenol added) or incubated at 62
      degrees C in presence of phenol. Nephelometry and gel SDS-PAGE techniques were
      used in assays that demonstrated the effects of phenol (denaturing) and the
      osmolytes (stabilizing) in horse antivenoms in high temperatures.

PMID- 9920479
TI  - Indirect cardiotoxic activity of the caecilian Siphonops paulensis (Gymnophiona,
      Amphibia) skin secretion.
AB  - The skin secretion of the caecilian S. paulensis has an indirect cardiotoxic
      effect. It induces a rapid blockage of electrical activity and subsequent
      diastolic arrest on in situ toad heart preparations. This action is not blocked
      by atropine and is therefore not mediated through a cholinergic mechanism. In
      addition, S. paulensis skin secretion is ineffective in inducing any response in
      isolated perfused toad heart assay, in the spontaneously beating isolated toad
      atria or in the electrically driven toad ventricle strip. These results, and the
      observation that S. paulensis skin secretion exhibits an hemolytic activity
      ([Schwartz, E. F., Schwartz, C. A., Sebben, A., Mendes E. G. (1997) Cardiotoxic
      and hemolytic activities on the caecilian Siphonops paulensis skin secretion. J.
      Venom. Anim. Toxins 3(1), 190]), suggest that the skin secretion cardiotoxicity
      could be mediated through an endogenous agent. The cardiotoxic action of S.
      paulensis skin secretion was investigated in isolated toad cardiac tissues in the
      presence of toad red blood cells (TRBC). In both atria and ventricle it evoked
      the same responses observed in the in situ heart. The potassium concentrations of
      the suspending media, as determined by atomic absorption spectroscopy were 9.5
      and 11.7 times greater, respectively, in the presence of TRBC than in its
      absence. Given that increased levels of potassium also showed a negative
      inotropic effect in the isolated ventricle strip, the action of the skin
      secretion was attributed to the hemolytic activity, which causesan increase in K+
      concentration of the medium.

PMID- 9920481
TI  - Action of mannitol in ciguatoxin-intoxicated rats.
AB  - This study reports the effects of mannitol on nerve conduction when used as a
      therapeutic agent in mammals following the administration of ciguatoxin.
      Electrophysiological studies were performed in vivo on the rat ventral coccygeal
      nerve. The absolute and relative refractory periods, conduction velocity and the
      supernormal response were measured in rats treated with i.p. ciguatoxin, both
      prior to, and following, the infusion of i.v. mannitol. Ciguatoxin induced
      significant prolongation of the absolute refractory period as well as significant
      slowing of the compound nerve conduction velocity. The magnitude of the
      supernormal response was significantly increased and the duration of the
      supernormal period extended in ciguatoxin-treated animals. Recordings collected
      following the infusion of mannitol in these ciguatoxin-treated animals showed
      that mannitol did not reverse the effects of ciguatoxin on nerve conduction in
      any of the parameters measured.

PMID- 9920480
TI  - Identification of putative palytoxin as the cause of clupeotoxism.
AB  - In 1994 in Madagascar a woman died after eating a sardine, Herklotsichthys
      quadrimaculatus. Two heads removed, respectively, from a toxic and a nontoxic
      fish before cooking were retrieved, kept frozen, and used for toxin analysis. The
      causative toxin was identified as palytoxin or its analogs based on its
      cytotoxicity, delayed hemolysis, neutralization with an anti-palytoxin antibody,
      chromatographic properties on different columns, and MS data. The gill and
      esophagus of the fish contained large amount of bottom sediments indicating that
      the fish had fed on the bottom and thus probably obtained the toxin from a
      benthic organism. The benthic dinoflagellate Ostreopsis siamensis that produces
      palytoxin and its analogs was inferred as the probable toxin source. This is the
      first study to shed light on clupeotoxism, a highly fatal form of human
      intoxication due to ingestion of clupeoid fish.

PMID- 9920482
TI  - Bioaccumulation of mycotoxins by shellfish: contamination of mussels by
      metabolites of a Trichoderma koningii strain isolated in the marine environment.
AB  - To determine whether toxic metabolites produced by fungi could cause shellfish
      toxicities, mussels were contaminated in laboratory conditions by sterile
      filtrates of a liquid culture of a strain of the fungus Trichoderma koningii
      previously isolated from a shellfish, the cockle (Cerastoderma edule). Mussels
      were kept in aerated natural seawater and fed with a culture of the microalga
      Isochrysis galbana, to which a filtrate of liquid fungal culture was added.
      Mussels were exposed to contamination for 7 days at 16 or 20 degrees C and
      extractions were then performed and their activity tested on blowfly larvae. The
      same toxicity was found in the fungal filtrate and the shellfish, indicating
      bioaccumulation. The digestive gland was the most toxic part of the mussel,
      confirming contamination by filtration. Treated mussels produced a mucus which
      appeared to be a means of eliminating toxic metabolites.

PMID- 9920483
TI  - Characterisation of cholera toxin by liquid chromatography--electrospray mass
      spectrometry.
AB  - Cholera toxin, one of the toxins that may be generated by various strains of the
      bacterium Vibrio cholerae, can be considered as a substance possibly used in
      biological warfare. The possibilities of characterising the toxin by liquid
      chromatography electrospray mass spectrometry (LC-ES-MS) were investigated. The
      toxin can be detected by flow-injection (FIA) ES-MS of a dialysed solution and
      observation of the charge envelope signals of its A-unit and B-chain protein;
      sufficient information for identification by the molecular mass of either protein
      could be obtained for quantities in the order of 10 fmol. Confirmatory analysis
      was carried out by 2-mercaptoethanol reduction and FIA-ES-MS detection of the
      product proteins or by tryptic digest LC-ES-MS with ion chromatogram detection of
      most of the tryptic fragments of the A-unit and B-chain from the singly, doubly
      or triply charged ion signals. The confirmatory tryptic digest LC-ES-MS analysis
      could be achieved with quantities as low as 1 pmol. Possible biovariations in the
      toxin can mostly be determined by sequencing, where the amino acid composition of
      tryptic fragments of the A1-chain, T5 and T15, and of the B-chain, T1, T4 and T5,
      cover all known biovariations. Partial sequencing of cholera toxin, originating
      from a classical strain, O1/569B, was achieved by LC-ES-MS/MS of most tryptic
      fragments larger than three amino acid residues.

PMID- 9920484
TI  - Effects of equinatoxin II from Actinia equina (L.) on isolated rat heart: the
      role of direct cardiotoxic effects in equinatoxin II lethality.
AB  - Equinatoxin II is a lethal basic protein isolated from the sea anemone Actinia
      equina (L.) with LD50 in mice 35 microg/kg. The putative cause of death is
      cardiorespiratory arrest, but the mechanism of cardiotoxicity is poorly
      understood. It is not clear whether the toxin injected intravenously into an
      experimental animal reaches the heart in a concentration sufficient to cause
      direct effects on the heart. Therefore experiments were performed on rats and on
      isolated rat hearts in order to investigate the possible direct cardiotoxic
      effects of the toxin. For this reason the hearts were perfused with different
      concentrations of the toxin and with the effluent from the lungs collected during
      perfusion of the lungs with equinatoxin II. The results revealed the clear dose
      dependent, direct cardiotoxic effects of the toxin and of the effluent from the
      lungs on Langendorff's heart preparations. The threshold concentration of
      equinatoxin II causing a drop in the perfusion rate, decreased left ventricular
      pressure, arrhythmia and increased LDH release, was found to be around 0.1 to 1
      nM. With 10 nM equinatoxin II the left ventricular pressure dropped to 14+/-11%
      of the control, and the coronary flow to 9+/-3%. These effects were followed by
      arrhythmia and cardiac arrest. The concentration of equinatoxin recovered from
      the lungs after the perfusion with 100 nM equinatoxin II ranged between 0.8 and 5
      nM. The results indicate that direct cardiotoxic effects of equinatoxin II play
      an important role in the lethal effects of the toxin.

PMID- 9920485
TI  - Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium
      channels.
AB  - Ciguatoxins (CTXs) and brevetoxins (PbTxs) modify the activation and inactivation
      processes of voltage-sensitive sodium channels (VSSC). In this study, the
      specific binding to rat brain synaptosomes of two commercial PbTxs, five purified
      CTXs and their derivatives was evaluated in competition with various
      concentrations of radiolabelled brevetoxin ([3H]PbTx-3). The results indicate
      that all CTXs bind specifically and with high affinity to sodium channels.
      Statistical analysis of the calculated inhibition constants identified two
      classes of toxins: the PbTxs and the less polar CTXs, and a group of CTXs of very
      high affinity. Relatively small chemical differences between the CTXs gave rise
      to significant differences in their affinity to the rat brain sodium channels.
      Cytotoxic effects associated with sodium channel activation were evaluated for
      the two classes of toxins on murine neuroblastoma cells, and their acute toxicity
      was determined in mice. CTXs have shown high affinities to VSSC of rat brain
      membranes and strong cytotoxic effects on neuroblastoma cells which correlate
      with their very low LD50 in mice. For PbTxs, it is different. Although binding
      with high affinity to VSSC and giving rise to significant cytotoxic effects, they
      are known to be poorly toxic intraperitoneally to mice. Furthermore, within the
      CTXs family, even though the most toxic compound (CTX-1B) has the highest
      affinity and the less toxic one (CTX-4B) the lowest affinity, a detailed analysis
      of the data pointed out a complex situation: (i) high affinity and toxicity seem
      to be related to the hydroxylation of the molecule on the A-ring rather than to
      the backbone type, (ii) acute toxicity in mice does not follow exactly the sodium
      dependent cytotoxicity on neuroblastoma cells. These data suggest that the high
      toxicity of CTXs is related to sodium-dependent disturbances of the excitable
      membranes but might also involve other cellular mechanisms.

PMID- 9920486
TI  - Comparative study of the cytolytic activity of myotoxic phospholipases A2 on
      mouse endothelial (tEnd) and skeletal muscle (C2C12) cells in vitro.
AB  - A rapid in vitro cytolytic effect of some myotoxic phospholipases A2 (PLA2s)
      isolated from the venoms of Viperidae snakes has been previously described. This
      study was undertaken to investigate if cytolytic activity is a common property of
      the myotoxic proteins from this group. Murine endothelial cells (tEnd) and
      skeletal muscle myotubes (C2C12) were utilized as targets. The release of lactic
      dehydrogenase was quantified as a measure of cell damage, 3 h after exposure of
      cells to the different PLA2s, including representatives from the genera Bothrops,
      Agkistrodon, Trimeresurus, Crotalus (family Viperidae), and Notechis (family
      Elapidae). All of the group II myotoxic PLA2s tested displayed rapid cytolytic
      activity when tested in the micromolar range of concentrations (8-32 microM). In
      contrast, the group I myotoxic PLA2 notexin was devoid of this activity.
      Aspartate-49 and lysine-49 PLA2 group II variants showed a comparable cytolytic
      effect. Skeletal muscle myotubes, obtained after fusion and differentiation of
      C2C12 myoblasts, were significantly more susceptible to the cytolytic action of
      myotoxins than endothelial cells, previously reported to be more susceptible than
      undifferentiated myoblasts under the same assay conditions. Cytolytic activity
      appears to be a common characteristic of group II myotoxic PLA2s of the
      Viperidae. Bee venom PLA2, a group III enzyme of known myotoxicity, also
      displayed cytotoxic activity on C2C12 myotubes, being devoid of activity on
      endothelial cells. These results suggest that in vitro differentiated skeletal
      muscle myotubes may represent a suitable model target for the study of myotoxic
      PLA2s of the structural group II found in snake venoms.

PMID- 9920487
TI  - Acute myocarditis following Tityus trinitatis envenoming: morphological and
      pathophysiological characteristics.
AB  - The clinicopathological features of four cases of scorpion envenoming by Tityus
      trinitatis are presented. The cardiac histopathology is recorded in the two fatal
      cases. The pathology of the acute myocarditis was a mixed picture of a toxic
      myocarditis and coagulative myocytolysis. These cardiac lesions are also seen in
      catecholamine induced cardiotoxicity and lend support to the theory that an
      adrenergic surge follows scorpion envenoming. A brief review of scorpion
      envenoming syndrome is undertaken in the light of these findings.

PMID- 9920488
TI  - Detection of an antibothropic fraction in opossum (Didelphis marsupialis) milk
      that neutralizes Bothrops jararaca venom.
AB  - An antibothropic fraction (ABF) from Didelphis marsupialis (opossum) serum, which
      is responsible for the neutralization of Bothrops jararaca venom was isolated by
      Perales et al. [Perales, J., Moussatche, H., Marangoni, S., Oliveira, B. and
      Domont, G. B. (1994). Isolation and partial characterization of an antibothropic
      complex from the serum of South American Didelphidae. Toxicon 32, 1237-1249]. The
      aim of this work was to verify the presence of this factor in opossum's milk,
      which could represent an additional protection for the neonatal opossum against
      bothropic venoms. An active milk fraction was isolated and showed similar
      physicochemical, structural, antigenic and biological properties when compared to
      ABF, indicating that they are probably the same protein.

PMID- 9920489
TI  - Tityus discrepans venom produces a respiratory distress syndrome in rabbits
      through an indirect mechanism.
AB  - It is well known that scorpion venom induces lung lesions and respiratory
      distress which are usually classified as pulmonary oedema (PO). Tityus discrepans
      is a scorpion that lives in the north-central area of Venezuela, is the most
      common source of human envenomation here and produces PO. We studied the action
      of the venom of Tityus discrepans on whole rabbits and on their isolated lungs
      perfused with Krebs saline with 1 g/l of bovine serum albumin (Krebs-BSA saline).
      Two milligram of venom were diluted in 250 ml of solution (approximately the
      rabbit's total blood volume) and used to perfuse isolated lungs. Lung oedema
      occurred in rabbits which received 1 mg/kg of scorpion venom i.p., heparin
      prevented the production of this lung oedema. T. discrepans venom produced PO, in
      rabbits pretreated with 15 mg/kg of ajoene. Yet, Tityus venom had no effects on
      isolated lungs perfused with citrated or heparinized blood, and in lungs perfused
      with Krebs-BSA with normal Ca2+. These result show that Tityus venom does not act
      directly on lungs. Otherwise, we have observed that abundant microthrombi
      occurred in all rabbit lungs exposed to venom in vivo, suggesting that these
      clotting alterations are fundamental to produce PO. The presence of intravascular
      microthrombi is not characteristic of the usual PO hinting that scorpion venom
      induced pulmonary alterations are a different clinical entity. We thus propose
      that the use of the term pulmonary oedema in scorpionism should abandoned in
      favor of scorpion venom respiratory distress syndrome.

PMID- 9920490
TI  - Complete nucleotide sequences of cDNAs encoding long chain alpha-neurotoxins from
      sea krait, Laticauda semifasciata.
AB  - This paper presents the nucleotide sequences of the cDNAs encoding two long chain
      alpha-neurotoxins from Laticauda semifasciata venom gland. The deduced amino acid
      sequences are Ls-III and its iso-neurotoxin.

PMID- 9920491
TI  - Direct evidence of transformation of dinophysistoxin-1 to 7-O-acyl
      dinophysistoxin-1 (dinophysistoxin-3) in the scallop Patinopecten yessoensis.
AB  - Non-toxic scallops Patinopecten yessoensis were reared for 5 days with the toxic
      dinoflagellate Dinophysis fortii sampled from the sea. The total cell number
      ingested by five scallops during the feeding experiment was approximately 682 x
      10(3). Okadaic acid (OA), dinophysistoxin-1 (DTX1) and esterified toxins of OA
      and DTX1 in D. fortii and scallop extracts were determined by liquid
      chromatography fluorescence detection (LC-FLD) as their 9-anthryldiazomethane
      (ADAM) derivatives. Only DTX1 was detected in D. fortii extracts used for the
      feeding experiment. The content of esterified DTXI in scallops fed on D. fortii
      was significantly higher than that of DTX1. Identification of esterified DTX1, 7
      O-palmitoyl DTX1 (7-O-16:0 DTX1), in D. fortii and scallop extracts was carried
      out by LC equipped with an atmospheric pressure electrospray ionization-mass
      spectrometry (ESI-MS). Only extracts of scallops fed on D. fortii yielded a mass
      spectrum exhibiting abundant [M-H]- at m/z 1055 corresponding to 7-O-16:0 DTX1.
      These findings are the first direct evidence of the transformation of DTX1 to 7-O
      acyl DTX1 in scallop tissues.

PMID- 9920492
TI  - Ability of wedelolactone, heparin, and para-bromophenacyl bromide to antagonize
      the myotoxic effects of two crotaline venoms and their PLA2 myotoxins.
AB  - We examined the ability of wedelolactone, heparin and para-bromophenacyl bromide
      to antagonize the myotoxic activity in mice of venoms from Crotalus viridis
      viridis and Agkistrodon contortrix laticinctus and two phospholipase A2
      myotoxins, CVV myotoxin and ACL myotoxin, isolated from them. Myotoxicity was
      measured by the increase in plasma creatine kinase (CK) activity at two hours and
      histological changes in extensor digitorum longus muscle (EDL) at three hours
      after injection of the test solution. Both heparin and wedelolactone
      independently reduced the myotoxic effect of both crude venoms and both
      myotoxins, but wedelolactone was more effective. Wedelolactone plus heparin
      reduced the myotoxic effect of CVV myotoxin more than either antagonist alone.
      The PLA2 inhibitor, para-bromophenacyl bromide (pBPB), reduced the myotoxic
      effect of both myotoxins more than either wedelolactone or heparin. On the other
      hand, the myotoxic effect of polylysine was not reduced by either wedelolactone
      or para-bromophenacyl bromide, but it was reduced by heparin. These results
      indicate that wedelolactone, para-bromophenacyl bromide and heparin are
      antagonists of these two phospholipase A2 myotoxins, and that antagonism by the
      first two compounds may be due to a more specific interaction with these proteins
      than that by the latter.

PMID- 9920493
TI  - Sex-linked variation of Loxosceles intermedia spider venoms.
AB  - In order to investigate intraspecific differences in Loxosceles intermedia spider
      venom we compared some biological properties of male and female venoms. Females
      produced higher amounts of venom than males. Furthermore, female venom presented
      more potent dermonecrotic and complement-dependent activities than male venom.
      Interestingly, the F35 toxin, a dermonecrotic and complement-dependent haemolytic
      factor, was also present in greater amounts in female venom, as demonstrated by
      ELISA. Therefore, the higher production and increased toxicity of venom in female
      specimens as compared to males may contribute to the variability observed in the
      severity of envenoming caused by L. intermedia spiders.

PMID- 9920494
TI  - A snake bite by the Burrowing Asp, Atractaspis engaddensis.
AB  - During routine milking of a group of Burrowing Asps Atractaspis engaddensis, one
      of the authors was bitten in the index finger by one fang, as is characteristic
      of bites by snakes of the genus. Local effects, oedema, erythema and numbness
      appeared within minutes, followed by systemic effects, including general
      weakness, sweating, pallor, fluctuations in the level of consciousness, vomiting
      and watery non-bloody diarrhoea. Gross oedema of the hand developed and extended
      up to the forearm. Two hours after admission to the hospital, blood pressure rose
      to 180/110, the ECG showed normal sinus rhythm and no signs of atrioventricular
      conduction block. An ECG obtained 24 h after the bite showed new T-wave
      inversions in leads V5 + 6, which gradually returned to baseline within several
      days. The local effects healed during the following weeks, but some discoloration
      and tenderness remained even 10 months after the bite. A maximal exercise (SPECT)
      study carried out five months after the bite was normal and a multigated
      radionuclear ventriculogram (MUGA) showed normal left-ventricular function. It
      may be assumed that the rise in blood pressure observed in this case reflects a
      systemic vasoconstrictive effect of the sarafotoxins, while the ST changes may
      have been caused by the direct effect of the toxins on the heart or indirectly by
      vasoconstriction of the coronary arteries. However, ischaemia secondary to a rise
      in blood pressure or to excitement could also explain the observed ECG-changes.

PMID- 9920496
TI  - Bibliography of toxinology.

PMID- 9920495
TI  - The smooth muscle relaxant effects of venom from the inland taipan (Oxyuranus
      microlepidotus).
AB  - Venom (10 microg/ml) relaxed phenylephrine-precontracted aortae. This relaxation
      was unaffected by removal of the endothelium or a combination of N(G)-nitro-L
      arginine (L-NOARG; 0.1 mM), oxyhaemoglobin (10 microM) and indomethacin (10
      microM). 4-BPB (0.78 mM), propranolol (1 microM), or a combination of apamin (0.1
      microM), charybdotoxin (0.1 microM) and glibenclamide (10 microM) did not effect
      endothelium-independent relaxation, suggesting a lack of PLA2 activity or an
      effect at beta-adrenoceptors or K+ channels. Venom (10 microg/ml) reversed Bay K
      8644 (0.1 microM)-induced contraction indicating the venom may have an effect on
      L-type Ca2+ channels.

PMID- 9920497
TI  - Calcium-independent release of neurotransmitter in the retina: a "copernican"
      viewpoint change.
AB  - The release of synaptic transmitter in chemical synapses is brought about by Ca2+
      influx through voltage-dependent Ca2+ channels opened by depolarisation of
      presynaptic terminals. However, in some preparations transmitter release persists
      or increases in low-Ca2+ media, and it has therefore been proposed that
      transmitter release could also occur through a Ca2+-independent, carrier mediated
      process. In particular it has been suggested that this may be the case for
      synaptic transmission between photoreceptors and second order neurones of the
      vertebrate retina. From our recent experiments on synaptic transmission from
      photoreceptors to horizontal cells of turtle and salamander retinas, it appears
      that lowering extracellular Ca2+ can actually promote Ca2+ influx through voltage
      activated Ca2+ channels via a modification of surface potential of plasma
      membranes. On the basis of this apparently paradoxical effect of low Ca2+ media,
      it is possible to reaccommodate the so-called Ca2+-independent release within the
      framework of Ca2+-dependent synaptic transmission without invoking unconventional
      mechanisms.

PMID- 9920498
TI  - Neuronal death in glaucoma.
AB  - Glaucoma is recognized to have its major detrimental effect upon the eye by
      killing retinal ganglion cells. The process of cell death appears to be initiated
      at the optic nerve head, though other sites of injury are possible but
      unsubstantiated. At present the injury at the nerve head seems related to the
      level of the eye pressure, but its detailed mechanism is as yet unexplained.
      There is a greater loss of ganglion cells from some areas of the eye, and this
      feature of glaucoma seems related to the regional structure of the supporting
      connective tissues of the optic nerve head. Larger retinal ganglion cells have
      been consistently shown to have somewhat greater susceptibility to injury in
      glaucoma, though all cells are injured, even early in the process. Ganglion cells
      die by apoptosis in human and experimental glaucoma, opening several potential
      areas for future therapies to protect them from dying. Neurotrophin deprivation
      is one possible cause of cell death and replacement therapy is a potential
      approach to treatment.

PMID- 9920499
TI  - Changes in Bruch's membrane and related structures with age.
AB  - Age-related macular disease is a major and growing public health burden in
      developed Caucasian societies, accounting for about 50% of blind registration.
      Evidence exists that this is an emerging problem in Eastern Asia, although the
      phenotype appears to differ from that seen in Western society. It is likely that
      several genes are involved, and that the genes or allelic variants conferring are
      common. Environment plays a major role in its pathogenesis, and it is believed
      that genetic susceptibility becomes apparent only if there are sufficient
      environmental pressures. There is no therapy currently available that will have
      an impact on the prevalence of blindness from age-related macular disease. It has
      been shown that visual loss occurs as a reaction to ageing changes in Bruch's
      membrane, which is interposed between the choriocapillaris and the retinal
      pigment epithelium. The age changes in all three structures have been partly
      characterised, and as a consequence, multiple putative pathogenic mechanisms have
      been proposed. Cross-sectional studies of populations with different genetic
      background and life styles would serve to prove the importance of inheritance and
      environment. Molecular genetic analysis of blood from affected sibling pairs from
      these sources may indicate the relevant genes, the prevalence of which may differ
      in different communities. Enquiries as to life styles may determine important
      environmental influences. Examination of donor eyes from these communities may
      reveal distinctive features that may reflect the variation in genetic
      predisposition and environmental pressures. It is hoped that the findings from
      such studies will lead to novel and potentially successful management strategies.

PMID- 9920500
TI  - Functional morphology of the trabecular meshwork in primate eyes.
AB  - The trabecular meshwork forms most of the resistance to aqueous humor outflow
      needed for maintenance of a pressure gradient between intraocular pressure of
      approximately 17 mmHg and venous pressure of approximately 10 mmHg. The
      composition of the extracellular material in the subendothelial or cribriform
      layer seems to be mainly responsible for outflow resistance. The aqueous humor
      pathways through the subendothelial layer can be influenced by ciliary muscle
      contraction and presumably also by contractile elements recently found both in
      trabecular meshwork and scleral spur. Pharmacologically induced disconnection of
      inner wall and cribriform cells leads to wash out of extracellular material
      through breaks of the endothelial lining of Schlemm's canal and to increase of
      outflow facility. In glaucomatous eyes the resistance to aqueous humor outflow is
      increased due to an increase in different forms of extracellular material
      deposited within the cribriform layer. The amount of this newly developed
      extracellular material is correlated with loss of axons in the optic nerve,
      indicating that a common factor is responsible for both changes. To investigate
      the effect of various factors on the biology of trabecular cells monolayer
      cultures derived from cribriform and corneoscleral trabecular meshwork have been
      established. The two cell lines can be differentiated because cribriform cells in
      vivo as in vitro stain for alphabeta-crystallin whereas the corneoscleral cells
      remain unstained. The effect of TGFbeta, a growth factor increased in aqueous
      humor of glaucomatous eyes and glycocorticoids on trabecular meshwork cells show
      typical changes in formation of extracellular matrix components and of stress
      proteins. Dexamethasone and oxidative damage also lead to increase of trabecular
      meshwork inducible glucocorticoid response (TIGR) protein. A mutation of the TIGR
      gene family has recently been found in families with juvenile and chronic simple
      glaucoma. Future research has to clarify the significance of these genetic
      factors for the pathophysiology of glaucoma and the role of trabecular cell
      activity in this respect.

PMID- 9920501
TI  - Predisposing factors for chronic angle-closure glaucoma.
AB  - Chronic angle-closure glaucoma is the commonest form of glaucoma in Sino
      Mongaloid populations. It is an anatomical disorder of the anterior segment of
      the eye characterised by permanent closure of part of the filtration angle as a
      result of iris apposition to the trabecular meshwork. Two pathways lead to this
      condition: recurrent pupillary block and "creeping" angle closure. East or
      Southeast Asian ethnic background is an important risk factor for the development
      of chronic angle-closure glaucoma. Other demographical risk factors include
      ageing, female gender and a familial tendency. Eyes with chronic angle-closure
      glaucoma have different anterior segment anatomical relationships when compared
      to normals. Those eyes at risk tend to be hypermetropic with a shallow anterior
      chamber, a relatively anteriorly positioned lens and a short axial length. The
      role of the ciliary body anatomy and ciliary processes in the pathogenesis of
      this condition requires further investigation.

PMID- 9920502
TI  - Oxysterols and atherosclerosis.
AB  - Oxysterols are present in human atherosclerotic plaque and are suggested to play
      an active role in plaque development. Moreover, the oxysterol:cholesterol ratio
      in plaque is much higher than in normal tissues or plasma. Oxysterols in plaque
      are derived both non-enzymically, either from the diet and/or from in vivo
      oxidation, or (e.g. 27-hydroxycholesterol) are formed enzymically during
      cholesterol catabolism. While undergoing many of the same reactions as
      cholesterol, such as being esterified by cells and in plasma, certain oxysterols
      in some animal and in vitro models exhibit far more potent effects than
      cholesterol per se. In vitro, oxysterols perturb several aspects of cellular
      cholesterol homeostasis (including cholesterol biosynthesis, esterification, and
      efflux), impair vascular reactivity and are cytotoxic and/or induce apoptosis.
      Injection of relatively large doses of oxysterols into animals causes acute
      angiotoxicity whereas oxysterol-feeding experiments have yielded contrary results
      as far as their atherogenicity is concerned. There is no direct evidence yet in
      humans that oxysterols contribute to atherogenesis. However, oxysterol levels are
      elevated in human low-density lipoprotein (LDL) subfractions that are considered
      potentially atherogenic and two recent studies have indicated that raised plasma
      levels of a specific oxysterol (7beta-hydroxycholesterol) may be associated with
      an increased risk of atherosclerosis. At the present time there are a number of
      significant and quite widespread problems with current literature which preclude
      more than a tentative suggestion that oxysterols have a causal role in
      atherogenesis. Further studies are necessary to definitively determine the role
      of oxysterols in atherosclerosis, and considering the wide-ranging tissue levels
      reported in the literature, special emphasis is needed on their accurate
      analysis, especially in view of the susceptibility of the parent cholesterol to
      artifactual oxidation.

PMID- 9920503
TI  - Recombinant apolipoproteins for the treatment of vascular diseases.
AB  - The protein components of human lipoproteins, apolipoproteins, allow the
      redistribution of cholesterol from the arterial wall to other tissues and exert
      beneficial effects on systems involved in the development of arterial lesions,
      like inflammation and hemostasis. Because of these properties, the
      antiatherogenic apolipoproteins, particularly apo A-I and apo E, may provide an
      innovative approach to the management of vascular diseases. The recent
      availability of extractive or biosynthetic molecules is allowing a detailed
      overview of their therapeutic potential in a number of animal models of arterial
      disease. Infusions of apo E, or more dramatically, of apo A-I, both recombinant
      or extractive, cause a direct reduction of the atherosclerotic burden in
      experimental animals. Naturally, as the apo A-I(Milano) (apo A-I(M)) dimer, or
      engineered recombinant apolipoproteins with prolonged permanence in plasma and
      improved function may offer an even better approach to the therapeutic handling
      of arterial disease. This progress will go on in parallel with innovations in the
      technologies for direct, non invasive assessments of human atherosclerosis, thus
      allowing closer monitoring of this potential new approach to therapy.

PMID- 9920504
TI  - Effects of a single local administration of cilostazol on neointimal formation in
      balloon-injured rat carotid artery.
AB  - To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP
      phosphodiesterase III, suppresses neointimal formation in balloon-injured carotid
      artery of the rat, 20 mg of cilostazol was topically applied using pluronic gel
      at the time of balloon injury. Rats were sacrificed 14 days after balloon injury
      to measure the extent of neointimal formation. Plasma and tissue concentrations
      of cilostazol were also measured at 1, 3, 7 and 14 days after topical
      application. The 5-bromo-2'-deoxyuridine (BrdU, a thymidine analogue) was given
      intraperitoneally to detect proliferation of smooth muscle cells in the injured
      media at 3 days after balloon injury. At 1 day after injury, plasma and tissue
      concentrations were 0.147+/-0.043 microg/ml and 1380 microg/g tissue. Although
      the plasma concentration of cilostazol was undetectable ( < 0.02 microg/ml), a
      significant amount of cilostazol (46 microg/g tissue) was still detected in the
      tissue at the site of application even after 2 weeks. The intimal area of the
      injured carotid after 2 weeks was significantly smaller in the cilostazol-treated
      group than in the gel-treated control group (0.06+/-0.01 vs 0.15+/-0.02 mm2,
      P<0.001). BrdU-positive smooth muscle cells in the injured media after 3 days
      were also significantly fewer in the cilostazol-treated group than in the gel
      treated control group (4.3+/-0.5 vs 9.1+/-0.9% of total cells, P < 0.001). These
      results suggest that local administration of cilostazol using pluronic gel
      maintains a high concentration of the drug at the application site, has an anti
      proliferative effect on smooth muscle cells, and may have potential for clinical
      therapeutic use for the prevention of restenosis following arterial intervention.

PMID- 9920505
TI  - Sublytic C5b-9 induces proliferation of human aortic smooth muscle cells: role of
      mitogen activated protein kinase and phosphatidylinositol 3-kinase.
AB  - Proliferation of vascular smooth muscle cells contributes to initimal hyperplasia
      during atherogenesis, but the factors regulating their proliferation are not well
      known. In the present study we report that sublytic C5b-9 assembly induced
      proliferation of differentiated human aortic smooth muscle cells (ASMC) in
      culture. Cell cycle re-entry occurred through activation of cdk4, cdk2 kinase and
      the reduction of p21 cell cycle inhibitor. We also investigated if C5b-9 cell
      cycle induction is mediated through activation of mitogen activated protein
      kinase (MAPK) pathways. Extracellular signal regulated kinase (ERK) 1 activity
      was significantly increased, while c-jun NH2-terminal kinase (JNK) 1 and p38 MAPK
      activity were only transiently increased. Pretreatment with wortmannin inhibits
      ERK1 activation by C5b-9, suggesting the involvement of phosphatidylinositol 3
      kinase (PI 3-kinase). Both PI 3-kinase and p70 S6 kinase were activated by C5b-9
      but not by C5b6. C5b-9 induced DNA synthesis was abolished by pretreatment with
      inhibitors of ERK1 and PI 3-kinase, but not by p38 MAPK. These data indicated
      that ERK1 and PI 3-kinase play a major role in C5b-9 induced ASMC proliferation.

PMID- 9920506
TI  - Macrophage released proteoglycans are involved in cell-mediated aggregation of
      LDL.
AB  - Aggregated low density lipoprotein (LDL) is taken up by macrophages at enhanced
      rate, leading to macrophage cholesterol accumulation and foam cell formation.
      Since macrophages were shown to mediate self aggregation of modified forms of
      LDL, we sought to study the effect of macrophages on the susceptibility of native
      LDL to aggregation. Incubation of LDL (100 microg of protein/ml) with J-774A.1
      macrophage-like cell line for 18 h at 37 degrees C, led to a 114 and 56% enhanced
      susceptibility of LDL to aggregation by vortexing and by Bacillus cereus SMase
      respectively. Macrophage conditioned media (MCMs) that were obtained from J
      774A.1 cells also enhanced the susceptibility of LDL to aggregation by vortexing
      and SMase by 134 and 75% respectively, suggesting the involvement of macrophage
      secretory products in the enhanced aggregation of LDL. As proteoglycans were
      shown to be involved in lipoprotein aggregation, we analyzed the possible
      involvement of macrophage-released proteoglycans in LDL aggregation. Incubation
      of LDL (100 microg protein/ml) with 25 microg of proteoglycans that were isolated
      from MCM led to a dose-dependent enhanced susceptibility of LDL to aggregation by
      vortexing or by SMase by up to 62 and 77% respectively. The stimulatory effect of
      the MCMs on LDL aggregation was markedly reduced upon MCMs treatment with the
      glycosaminoglycan hydrolyzing enzyme chondroitinase ABC, chondroitinase AC, but
      not heparinase. On the contrary, incubation of LDL (100 microg of protein/ml)
      with increasing concentrations (up to 50 microg/ml) of chondroitin sulfate, or
      heparan sulfate enhanced the susceptibility of LDL to aggregation by up to 98 or
      by only 18% respectively, in comparison with non-treated LDL. Since macrophages
      under atherogenic conditions (cholesterol-loading, cellular lipid peroxidation
      and activation) demonstrate enhanced secretion of proteoglycans, we finally
      studied the effect of J-774A.1 macrophages on the susceptibility of native LDL to
      aggregation under the above atherogenic conditions. Incubation of LDL with
      cholesterol-loaded macrophages led to a 62% enhanced susceptibility of LDL to
      undergo aggregation by vortexing, in comparison with LDL that was incubated with
      non-loaded cells. Macrophage activation with phorbol myristate acetate (5 microM
      of PMA) also significantly increased cell-mediated aggregation of LDL by 50%, in
      comparison with non-activated cells. Lipid peroxidized macrophages obtained by
      cell treatment with either FeSO4 (50 microM), or angiotensin II (10(-7) M)
      enhanced the susceptibility of LDL to aggregation by 22 or by 39% respectively.
      These results suggest that under atherogenic conditions, macrophages release
      proteoglycans, and mainly chondroitin sulfate, which can contribute to cell
      mediated formation of aggregated LDL, a potent inducer of macrophage foam cells
      which are the hallmark of early atherogenesis.

PMID- 9920507
TI  - Increased advanced glycation end products in atherosclerotic lesions of patients
      with end-stage renal disease.
AB  - Although advanced glycation end products (AGEs) are increased in the serum and
      tissues of patients with end-stage renal disease, little is known about the role
      of AGEs in atherogenesis. We therefore carried out an immunohistochemical study
      on the accumulation of AGEs and apolipoprotein B in the human aortas of diabetic
      and nondiabetic subjects with end-stage renal disease. The atherosclerotic
      lesions included diffuse intimal thickening, fatty streaks and atherosclerotic
      plaque. We used antibodies against two different epitopes of AGE structures, i.e.
      an Nepsilon-(carboxymethyl)lysine-protein adduct (CML) and a structure(s) other
      than CML (nonCML). The area that was positive for an antigen as a percentage of
      the total area (%Ar) was determined morphometrically, using an NIH-image program.
      In diffuse intimal thickening, atherosclerotic plaque and tunica media, the %Ar
      of CML and nonCML was significantly greater in diabetic or nondiabetic subjects
      with end-stage renal disease than in control subjects without end-stage renal
      disease. In fatty streaks, the %Ar of nonCML was significantly greater in
      nondiabetic subjects with end-stage renal disease than in control subjects, while
      no difference in the %Ar of CML was found between the subjects with or without
      end-stage renal disease. Nondiabetic subjects with end-stage renal disease showed
      a significantly increased %Ar of apolipoprotein B in fatty streaks and
      atherosclerotic plaque than the control subjects. The %Ar of CML and nonCML
      significantly correlated with the duration of hemodialysis in diffuse intimal
      thickening and atherosclerotic plaque of subjects with end-stage renal disease,
      but not in fatty streaks. On the other hand, the %Ar was not related to the
      duration of diabetes in any of the lesions in the diabetic subjects with end
      stage renal disease. In diffuse intimal thickening and atherosclerotic plaque,
      subjects with end-stage renal disease showed a significant correlation between
      the %Ar of apolipoprotein B and AGEs (CML and nonCML), as well as their
      immunohistochemical colocalization. These results suggest that impaired AGE
      clearance may cause the increased accumulation of AGEs in the aortic wall of
      subjects with end-stage renal disease, thus resulting in the rapid progression of
      atherosclerosis. The accumulation of AGEs may be related to an enhanced LDL
      deposition in atherosclerotic lesions of subjects with end-stage renal disease.

PMID- 9920508
TI  - Linkage analysis of candidate genes and the small, dense low-density lipoprotein
      phenotype.
AB  - There is accumulating evidence for the importance of small, dense low-density
      lipoprotein (LDL), the defining feature of the atherogenic lipoprotein phenotype,
      as a risk factor for coronary heart disease. Although both family studies and
      twin studies have demonstrated genetic influences on this phenotype, the specific
      gene(s) involved remain to be identified. The purpose of this study was to
      determine whether there was evidence for genetic linkage between small, dense LDL
      (LDL subclass phenotype B), as determined by gradient gel electrophoresis, and
      selected candidate genes known to be involved in lipid metabolism. The linkage
      analyses were based on a sample of 19 families, including 142 individual family
      members, using a lod score linkage analysis approach. Nine candidate genes were
      examined, including loci for manganese superoxide dismutase (Mn SOD2),
      apolipoproteins CIII, AII, and apo CII, lipoprotein lipase, hepatic lipase,
      microsomal triglyceride transport protein, the insulin receptor and the LDL
      receptor. The analyses did not provide significant evidence for genetic linkage
      between markers for any of these genes and LDL subclass phenotype B, nor did it
      confirm previous reports of linkage between the LDL receptor gene and LDL
      subclass phenotype B. Using three closely linked markers for the Mn SOD2 locus
      excluded close linkage between this candidate gene region and LDL subclass
      phenotype B. These findings demonstrate the complexity of genetically mapping
      risk factor phenotypes, and emphasize the necessity of identifying new genetic
      loci, other than known candidate genes, involved in susceptibility to
      atherosclerosis.

PMID- 9920509
TI  - Lipoprotein lipase greatly enhances the retention of lipoprotein(a) to
      endothelial cell-matrix.
AB  - The trapping of apolipoprotein (apo)B containing lipoproteins within the arterial
      subendothelial matrix (ECM) is an early event in atherosclerosis. When
      lipoprotein lipase, a constituent of the ECM, is prebound to ECM both LDL and
      oxidized LDL binding is greatly enhanced. In this study we compared the binding
      of lipoprotein(a) (Lp(a)), a lipoprotein correlated with atherosclerosis and
      restenosis, to ECM in the presence of varying concentrations of LPL. Without LPL,
      Lp(a) binding was low and non-saturable. In the presence of LPL, Lp(a) retention
      increased from 2.7 x 10(-7) to 1.13 x 10(-4) nmoles. Scatchard analysis
      demonstrated that the affinities of both Lp(a) and LDL to lipase were similar. In
      competition experiments, LDL, apoE, polymers of lysine and arginine were all
      capable of preventing the lipase specific [125I]Lp(a) retention. However, neither
      collagen nor fibronectin were capable of blocking or displacing [125I]Lp(a) from
      the lipase bound to ECM. In a separate set of experiments, when ECM was not
      saturated with lipase, both fibronectin and collagen (at 10-fold protein excess)
      prevented approximately 40% of total [125I]Lp(a) retention to ECM. These data
      suggest, in the absence of lipase, apo(a) may regulate the binding of Lp(a) to
      ECM. Whereas, lipase enhanced the binding of Lp(a) to ECM, most probably through
      the apoB moiety of the Lp(a) particle.

PMID- 9920511
TI  - Mortality in treated heterozygous familial hypercholesterolaemia: implications
      for clinical management. Scientific Steering Committee on behalf of the Simon
      Broome Register Group.
AB  - Clinical management of heterozygous familial hypercholesterolaemia is largely
      based on evidence from a small number of observational studies and extrapolation
      from the results of clinical trials of lipid-lowering in patients with polygenic
      hypercholesterolaemia The objectives of this study were (i) to determine the
      absolute and relative mortality of patients with treated heterozygous familial
      hypercholesterolaemia, (ii) to estimate the effect of changes in treatment
      efficacy on mortality trends over time, and (iii) to examine the implications of
      these findings for patient management. A cohort of 605 men and 580 women aged 20
      79 years with heterozyous familial hypercholesterolaemia were recruited from 21
      out-patient lipid clinics in the UK. Patients were followed prospectively from
      1980 to 1995 for 8770 person-years. Absolute mortality was calculated, and
      relative risk was expressed as the ratio of the number of observed deaths to the
      number expected in the general population of England and Wales. Forty six of the
      73 deaths were due to coronary heart disease. In women aged 20-39, despite
      treatment, the relative risk of a fatal coronary event was increased 125-fold
      (95% confidence intervals 15-451) and the annual coronary mortality was 0.17%. In
      men aged 20-39 the relative risk was increased 48-fold (17-105) and the annual
      coronary mortality was 0.46%. The relative risk decreased with age but the
      absolute risk increased. For men and women aged 60-79, the annual coronary
      mortality was 1.1% representing a significant excess mortality for women
      (relative risk 2.6, 1.3-4.5) but not for men (RR 1.1, 0.5-2.3). Non-coronary
      mortality was not increased at any age (RR for all ages 0.68, 0.45-0.99). There
      was a decline in the relative risk for coronary mortality in patients aged 20-59
      from an eight-fold (4.8-7.2) increased risk before 1992 to 3.7 (1.6-7.2.)
      thereafter (P=0.08). The results suggest that the prognosis for patients with
      heterozygous familial hypercholesterolaemia has improved with the introduction of
      more effective treatment, and that lipid-lowering therapy is not associated with
      increased non-coronary mortality. These findings and the excess coronary
      mortality observed suggest that all affected adult men and post-menopausal women
      should be treated with HMG-CoA reductase inhibitors.

PMID- 9920510
TI  - Lovastatin maintains nitric oxide--but not EDHF-mediated endothelium-dependent
      relaxation in the hypercholesterolemic rabbit carotid artery.
AB  - The endothelium contributes to the regulation of vascular tone by producing
      nitric oxide (NO) and the endothelium-derived hyperpolarising factor (EDHF). In
      hypercholesterolemia, endothelium-dependent relaxation is impaired but can be
      restored by treatment with lovastatin (LOVAS). We investigated the effects of
      LOVAS on NO and EDHF-mediated relaxation. Rabbits were fed 1% cholesterol diet
      for 4 weeks and 0.5%) cholesterol for the following 12 weeks (CHOL-group). The
      LOVAS group additionally received 10 mg of lovastatin over the last 12-week
      period. Experiments were performed in carotid artery rings. Relaxant responses to
      acetylcholine (ACh) were recorded in the presence of indomethacin. Nitro-L
      arginine (NOARG, 100 microM) and potassium chloride (KCl, 35 mM) were used to
      differentiate between NO- and EDHF-mediated relaxations. Cholesterol impaired ACh
      induced relaxations and this effect was prevented by LOVAS (control 100+/-1%,
      CHOL 81+/-6%, LOVAS 98+/-1%). In the presence of NOARG, relaxations to ACh were
      not different between the LOVAS and CHOL groups (control 78+/-4%, CHOL 64+/-6%,
      LOVAS 64+/-5%). When KCl was used, ACh-induced relaxations were similar in the
      LOVAS and control group (control 75+/-5%, CHOL 49+/-6%, LOVAS 76+/-2%). In
      arteries treated with NOARG and KCl together, no relaxations were observed.
      Relaxations of arteries from the control group were not affected by 18 h
      preincubation with lovastatin (10 microM). Lovastatin selectively maintains
      nitric oxide-mediated endothelium-dependent relaxation in hypercholesterolemic
      rabbit carotid arteries.

PMID- 9920512
TI  - Low density lipoprotein particle diameter in young, nonobese, normolipidemic
      Japanese men.
AB  - BACKGROUND: prospective studies have demonstrated that a predominance of small,
      dense LDL particles (pattern B) precedes the clinical onset of coronary heart
      disease. Prevalence and characteristics of subjects with this LDL size
      abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS
      AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc
      polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20
      years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29
      mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with
      small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%)
      had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top
      tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum
      levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs
      49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower
      HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index
      (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/
      4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002)
      and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride
      (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index
      (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20,
      P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol,
      apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even
      in young, nonobese, normolipidemic men, LDL size appears to be associated with
      triglyceride-rich lipoprotein metabolism and body fat.

PMID- 9920513
TI  - Accumulation of co-localised unesterified cholesterol and neutral lipids within
      vacuolised elastin fibres in athero-prone areas of the human aorta.
AB  - To investigate whether there are alterations of elastin fibres in the arterial
      intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic
      aorta were taken soon after death from 13 healthy trauma victims whose ages
      ranged from 16 to 40 years. Two areas were compared: atherosclerosis-prone (AP)
      areas localised to the dorsal aspect of the aorta along the rows of intercostal
      branch origins, and atherosclerosis-resistant (AR) areas from the ventral aorta.
      Electron microscopic analysis combined with cytochemical staining was applied.
      Unesterified cholesterol was identified using the filipin-staining technique
      while neutral lipids were visualised by the OTO-technique. Intimal features were
      studied by combining the filipin-staining and the OTO-technique. Electron
      microscopical examination showed that in both AR and AP areas, some elastin
      fibres in the intima were vacuolised. Unesterified cholesterol was found to be
      predominantly localised in the musculoelastic layer, in particular, inside the
      vacuolised elastin fibres. This localisation was seen in all 13 AP areas studied
      in contrast to the AR areas where it was observed in only four of 13 aortas
      studied (P < 0.0005, chi2-test). Accumulation of neutral lipids inside vacuolised
      elastin fibres was found in five out of 13 AP areas but was not observed in any
      of the AR areas (P=0.01, chi2). A combination of the filipin-staining and OTO
      techniques showed that some deposits of neutral lipids and unesterified
      cholesterol within vacuolised elastin fibres were independently located from each
      other, but more frequently, neutral lipids were co-located with unesterified
      cholesterol. The present observations indicate a difference between AP and AR
      intimal areas which, in particular, relates to the structure of elastin fibres in
      the musculoelastic layer. The observations suggest that alterations of the
      extracellular matrix are involved in the trapping and retention of cholesterol
      and neutral lipids within the intima at an early stage in the development of
      atherosclerotic lesions.

PMID- 9920514
TI  - Milrinone, a phosphodiesterase inhibitor, suppresses intimal thickening after
      photochemically induced endothelial injury in the mouse femoral artery.
AB  - The effect of milrinone, a phosphodiesterase (PDE) inhibitor, on intimal
      thickening after endothelial denudation was investigated. Intimal thickening was
      induced in the femoral arteries of mice by a photochemical reaction between rose
      bengal and transluminal green light which caused endothelial injury followed by
      platelet adhesion, aggregation, and formation of an occlusive thrombus in the
      irradiated segment of the mouse femoral artery. In this model, intimal thickening
      occurred following spontaneous thrombolysis. The intima/media ratio at 21 days
      after irradiation was 0.556+/-0.104 in the untreated group. Oral administration
      of milrinone (0.3-3.0 mg/kg) for 3-21 days suppressed intimal thickening by up to
      56% in a dose- and time-dependent manner. In an in vivo experiment using
      bromodeoxyuridine incorporation, milrinone suppressed cell proliferation at 1.0
      mg/kg p.o. On the other hand, the minimum doses of milrinone for suppression of
      ex vivo platelet aggregation induced by collagen (0.8 microg/ml) or ADP (0.5
      microM) were 3.0 and 10.0 mg/kg, respectively. These results indicate that
      milrinone may not suppress intimal thickening by inhibiting platelet function but
      by preventing vascular smooth muscle cell (VSMC) proliferation, probably through
      a mechanism mediated via 3', 5'-adenosine cyclic monophosphate (cAMP).

PMID- 9920515
TI  - Proanthocyanidin-rich extract from grape seeds attenuates the development of
      aortic atherosclerosis in cholesterol-fed rabbits.
AB  - The aim of this study was to evaluate the antiatherosclerotic effect of
      proanthocyanidin-rich extracts from grape seeds in cholesterol-fed rabbits.
      Proanthocyanidin-rich extracts (0.1% and 1% in diets [w/w]) did not appreciably
      affect the changes in serum lipid profile of cholesterol-fed rabbits. The level
      of cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2'-azobis(2
      amidinopropane-dihydrochloride (AAPH) were lower in the plasma of rabbits fed
      proanthocyanidin-rich extract plus cholesterol than in the plasma of rabbits fed
      cholesterol alone, but not in the low-density lipoprotein (LDL). Aortic
      malondialdehyde (MDA) content decreased in rabbits fed proanthocyanidin-rich
      extract. Feeding proanthocyanidin-rich extracts (0.1 and 1% in the diet) to
      rabbits significantly reduced severe atherosclerosis in the aorta.
      Immunohistochemical analysis revealed a decrease in the number of oxidized LDL
      positive macrophage-derived foam cells in atherosclerotic lesions in the aorta of
      rabbits fed proanthocyanidin-rich extract. When proanthocyanidin-rich extract was
      administered orally to rats, proanthocyanidin was detected in the plasma by
      Porters method but not in the lipoproteins (LDL plus VLDL). In an in vitro
      experiment using human plasma, proanthocyanidin-rich extract added to the plasma
      inhibited the oxidation of cholesteryl linoleate in LDL, but not in the LDL
      isolated after the plasma and the extract were incubated in advance. These
      results suggested that proanthocyanidins, the major polyphenols in red wine,
      might trap reactive oxygen species in aqueous series such as plasma and
      interstitial fluid of the arterial wall, thereby inhibiting oxidation of LDL and
      showing an antiatherosclerotic activity.

PMID- 9920516
TI  - The effects of structurally defined triglycerides of differing fatty acid
      composition on postprandial haemostasis in young, healthy men.
AB  - The aim of this study was to investigate whether a number of key haemostatic
      factors were altered when healthy young individuals were challenged with a fat
      load of physiological size contained within a meal composed of normal ingredients
      and whether this response was modified when the fatty acid composition of the
      meal was altered radically. Eight healthy male volunteers each randomly consumed
      four meals which were identical in terms of gross nutritional content (41% of
      energy provided as fat, 17% as protein and 42% as carbohydrate) but which
      differed in fatty acid composition. To reduce the possible influence of fatty
      acid position within the triglyceride molecule on lipid absorption and subsequent
      metabolic effects, the structural integrity of 91% of fat (test triglycerides
      such as 1,3 distearoyl-2-oleoyl glycerol (S-O-S), trioleine (O-O-O), and 1,3
      dilinoleoyl-2-oleoyl glycerol, (L-O-L)) in the meals was controlled so that the
      principal fatty acid in the sn-2 position was oleic acid (18:1n-9). Meals rich in
      either a test triglyceride or a control oil provided 44+/-6 g of fat. No
      significant alterations from fasted values of elevated plasma factor VII
      coagulant activity (FVIIc) or F1 + 2 were observed. FVIIA varied significantly
      over the postprandial time course; however, when expressed as a percentage of the
      fasting value, the FVIIa responses to O-O-O and L-O-L differed significantly but
      this was not evident when the absolute values were analysed. Similarly, no
      difference in plasma fibrinopeptide A (FPA) concentrations were evident. After
      all four meals, chylomicron contained proportionately more palmitic acid and
      generally less oleic acid than the ingested lipids. This study clearly
      demonstrates that postprandial haemostatic responses of young healthy individuals
      to a physiological fat load are minimal, (irrespective of triglyceride
      structure).

PMID- 9920517
TI  - Comparison of the effects of two low fat diets with different alpha
      linolenic:linoleic acid ratios on coagulation and fibrinolysis.
AB  - Fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have
      been demonstrated to alter coagulation and fibrinolysis variables. This study
      compared the effects of a traditional cholesterol-lowering diet and a similar
      diet, which had 50% of the linoleic acid (LA) replaced with the 18 carbon n-3
      fatty acid, alpha-linolenic acid (ALA), on selected hemostatic variables. After a
      2-week run-in diet with 39.5% total energy (en) from fat, 29 healthy male
      subjects consumed a 31.5% en fat diet with approximately 7% en from
      polyunsaturated fat and an ALA:LA ratio of either 1:1.2 (ALA-rich, n=15) or 1:21
      (LA-rich, n=14) for 6 weeks. Blood was collected at the beginning, middle and end
      of test diets for analysis of Factor VIIc and VIIIc, fibrinogen, von Willebrand
      factor, activated protein C resistance (APC resistance), tissue plasminogen
      activator and plasminogen activator inhibitor type-1 activities and/or protein
      concentrations and platelet fatty acids. The ALA-rich diet tripled the percentage
      of platelet EPA, (P < 0.0005) but had little effect on coagulation and
      fibrinolysis. The APC ratio demonstrated increased anticoagulant activity on the
      ALA-rich diet (P < 0.001) only. Studies in patients with vascular pathologies are
      indicated to corroborate the current findings. Greater ratios of ALA:LA,
      achievable only with greater amounts of polyunsaturated fat, may be necessary to
      produce the effects demonstrated after feeding fish oils.

PMID- 9920518
TI  - Probucol selectively increases oxidation of atherogenic lipoproteins in
      cholesterol-fed mice and in Watanabe heritable hyperlipidemic rabbits.
AB  - The anti-atherogenic and cholesterol-lowering drug probucol (0.5-1%) or quercetin
      (1%), a natural antioxidant, was given to cholesterol-fed (1.5%) mice for a
      period of 6 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for a
      period of 8 weeks to investigate the oxidative changes in plasma and
      lipoproteins. Oxidation was measured as the total amount of malondialdehyde (nmol
      MDA/g protein) by a very specific MDA-HPLC method. A large and significant
      increase in MDA was seen in LDL from probucol treated WHHL rabbits (1778.7+/
      585.5 nmol/g vs. 394.4+/-144.5 nmol/g, P < 0.001) and cholesterol-fed mice (579.7
      + 47.3 nmol/g vs. 408.1+/-85.8 nmol/g, P < 0.05) as compared to controls while
      LDL cholesterol was lowered (WHHL rabbits: P < 0.05; mice: P < 0.01). In WHHL
      rabbits VLDL oxidation was determined additionally, and also revealed a large
      increase in the probucol group (2102.7+/-1156.1 nmol/g vs. 455.0+/-207.8 nmol/g,
      P< 0.01). In contrast, the oxidation of plasma and HDL from probucol treated
      animals was not statistically significantly increased, implying that probucol
      mediates a selective oxidation of atherogenic cholesterol-transporting
      lipoproteins. Quercetin treated animals did not show increased oxidation of LDL
      (and VLDL in rabbits) and cholesterol levels were not decreased. Furthermore, no
      protective antioxidant effect of quercetin was seen. In conclusion, the results
      suggest that a prooxidant mechanism rather than antioxidative effects influences
      lipoprotein metabolism in these animals. It is hypothesized that the oxidation of
      lipoproteins might be a physiological mechanism performed by macrophages or other
      cells for uptake and degradation (by macrophages and liver) of excessive amounts
      of LDL or VLDL and that probucol oxidizes atherogenic lipoproteins and thereby
      leads to a decrease in cholesterol levels.

PMID- 9920519
TI  - Possible role of high susceptibility of high-density lipoprotein to lipid
      peroxidative modification and oxidized high-density lipoprotein in genesis of
      coronary artery spasm.
AB  - Recent study demonstrated high susceptibility of plasma LDL to lipid peroxidative
      modification in patients with variant angina. Oxidized stress state, especially
      oxidized LDL, may induce coronary artery spasm by its impairing effect of
      endothelium-dependent arterial relaxation, but precise mechanisms remain unclear.
      Study subjects included 93 patients who underwent coronary angiographic
      examination: 12 patients with coronary artery spasm provoked by ergonovine
      without organic stenosis (group I), 11 patients who did not demonstrate coronary
      artery spasm or organic stenosis (group II) and 70 patients with organic coronary
      artery stenosis (group III). Levels of plasma HDL-cholesterol and apoA-I in group
      I were similar to those in III but were significantly lower than those in II,
      although the other plasma lipid parameters were not different among the three
      groups. The levels of TBARS in plasma and HDL were significantly higher in group
      I than in II or III (2.94+/-1.56 vs. 1.91+/-0.35 or 2.23+/-0.89 nmol MDA/ml and
      1.23+/-1.00 vs. 0.54+/-0.37 or 0.70+/-0.63 nmol MDA/mg protein; P < 0.05),
      although the levels of TBARS in LDL were not significantly different. In the
      monitoring curve of diene production during copper-induced lipid peroxidation of
      HDL, its propagation slope was steeper and levels of maximum diene absorbance was
      higher in group I as compared with that in II or III, but not found in those of
      LDL. These results suggested that high susceptibility of HDL to lipid
      peroxidative modification in group I may contribute to the genesis of coronary
      artery spasm, and oxidized HDL rather than oxidized LDL is more likely to be
      related to coronary artery spasm.

PMID- 9920520
TI  - Comparative effects of polyunsaturated- to saturated fatty acid ratio versus
      polyunsaturated- and monounsaturated fatty acids to saturated fatty acid ratio on
      lipid metabolism in rats.
AB  - This study examined the effects of various polyunsaturated fatty acid (PUFA,
      P)/saturated fatty acid (SFA, S) ratio versus PUFA + monounsaturated fatty acid
      (MUFA, M)/SFA ratio on lipid metabolism. The P/S ratio of dietary fat was fixed
      at a certain level (0.5, 1, 2, or 4, respectively) for each of four pairs of rat
      groups respectively, and then the P + M/S ratio was changed for the four pairs of
      rat groups. When the P/S ratio was fixed at 0.5, 1, 2, or 4, the plasma total
      cholesterol, LDL-cholesterol (C), and HDL-C levels did not show any significant
      difference in each pair of groups with different P + M/S ratios. However, when
      the P/S ratio was fixed at 1.0, the higher P + M/S ratio of 5.7 (M/S=4.7,
      P/M=0.2) resulted in significantly higher plasma total triacylglycerol (TAG),
      VLDL-TAG, VLDL-C, and VLDL-phospholipid (PL) than the lower P + M/S ratio of 1.4
      (M/S=0.4, P/M=2.4). Whereas when SFA was fixed at a similar level, it therefore
      had approximately the same P + M/S ratio(5.3, 5.6, 5.7), and by increasing the
      P/S ratio from 1, 2 to 4 (70.4, 52.7 and 23.2% of the total fatty acids as MUFA
      respectively), the plasma VLDL-C, VLDL-TAG, and VLDL-PL concentrations decreased
      progressively. When PUFA or MUFA was kept on a similar level (14.9 or 53%
      respectively), the higher P + M/S ratio (5.7 or 5.3, respectively) resulted in
      significantly greater accumulation of liver cholesterol than the lower P + M/S
      ratio of 2.2. When the P/S ratio was fixed at 1 or 4, the diet of higher P + M/S
      ratio in a pair of the groups also resulted in greater accumulation of liver
      cholesterol. The results of the study suggests that if the P + M/S ratio was
      below 3, the change in the P/S ratios (0.5, 1 or 2) did not affect the levels of
      plasma total and lipoprotein cholesterol and TAG. Increases in the plasma VLDL-C
      and VLDL-TAG were related to increased MUFA content in the diet. And high MUFA
      content resulted in greater accumulation of liver cholesterol. It seems that the
      prerequisites for keeping low plasma and liver cholesterol are (a) low M/S ratio
      and (b) high P/M ratio and (c) P + M/S ratio not to exceed 3.

PMID- 9920521
TI  - Circulating cell adhesion molecules and endothelial markers before and after
      transluminal angioplasty in peripheral arterial occlusive disease.
AB  - In the present study, the levels of soluble adhesion molecules P- and E-selectin,
      intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1)
      and of other markers of endothelial activation or injury, such as thrombomodulin,
      von Willebrand factor (vWF), as well as homocysteine, were prospectively
      investigated in 71 patients (21 women, 50 men, age 68+/-13) with predominantly
      femoropopliteal peripheral arterial occlusive disease (PAOD, stage II-IV,
      Fontaine) before and after percutaneous transluminal angioplasty (PTA). Thirty
      patients (42.3%) developed restenosis within 6 months, defined as a > 50%
      reduction of the lumen diameter at the site of PTA. At entry in the study, 46%
      and 58% of all patients had higher than normal levels of soluble P-selectin and
      VCAM-1, respectively. Thrombomodulin (P < 0.01) measured at entry, was
      significantly higher in patients who developed late restenosis, with trends for
      higher values for P-selectin, VCAM-1 and vWF. The relative risks for developing
      restenosis were 2.41 (CI95%: 1.23-4.75) and 1.54 (CI95%: 0.98-2.72) for
      thrombomodulin and P-selectin, respectively. Soluble P-selectin and the severity
      of PAOD (Fontaine stage III/IV) were found to be statistically indicative factors
      for late restenosis in a logistic regression risk factor analysis with an overall
      predictive value of 72%. At 6 months, those who developed restenosis had also
      higher soluble P-selectin (P < 0.01), VCAM-1 (P < 0.05) and a trend for higher
      thrombomodulin. Homocysteine was elevated in 52% of the patients at entry but
      neither was it associated with higher restenosis rates nor did it correlate with
      the levels of thrombomodulin or the other adhesion molecules. These findings
      indicate that patients with PAOD have to a significant proportion, elevated
      levels of circulating soluble adhesion molecules and markers of endothelial
      activation occurring in concert with an ongoing atherosclerotic process.

PMID- 9920522
TI  - Relationship between plasma phospholipid transfer protein activity and HDL
      subclasses among patients with low HDL and cardiovascular disease.
AB  - Low levels of high density lipoproteins (HDL) are associated with an increased
      risk for premature cardiovascular disease. The plasma phospholipid transfer
      protein (PLTP) is believed to play a critical role in lipoprotein metabolism and
      reverse cholesterol transport by remodeling HDL and facilitating the transport of
      lipid to the liver. Plasma contains two major HDL subclasses, those containing
      both apolipoproteins (apo) A-I and A-II, Lp(A-I, A-II), and those containing apo
      A-I but not A-II, Lp(A-I). To examine the potential relationships between PLTP
      and lipoproteins, plasma PLTP activity, lipoprotein lipids, HDL subclasses and
      plasma apolipoproteins were measured in 52 patients with documented
      cardiovascular disease and low HDL levels. Among the patients, plasma PLTP
      activity was highly correlated with the percentage of plasma apo A-I in Lp(A-I)
      (r=0.514, p < 0.001) and with the apo A-I, phospholipid and cholesterol
      concentration of Lp(A-I) (r=0.499, 0.478, 0.457, respectively, p < 0.001). Plasma
      PLTP activity was also significantly correlated with plasma apo A-I (r=0.413,
      p=0.002), HDL cholesterol (r=0.308, p=0.026), and HDL, and HDL3 cholesterol
      (r=0.284 and 0.276, respectively, p < 0.05), but no significant correlation was
      observed with Lp(A-I, A-I), plasma cholesterol, triglycerides, or apo B, very low
      density lipoprotein cholesterol or low density lipoprotein cholesterol. These
      associations support the hypothesis that PLTP modulates plasma levels of Lp(A-I)
      particles without significantly affecting the levels of Lp(A-I, A-II) particles.

PMID- 9920523
TI  - Association of Helicobacter pylori infection with elevated serum lipids.
AB  - Helicobacter pylori causes a chronic gastric infection, which has been associated
      with coronary heart disease. To evaluate the mechanisms of this association, we
      studied whether the infection affects serum lipid levels as previously shown in
      acute infections. We analysed the serum samples of 880 males who participated in
      a reindeer herders' health survey in Northern Finland in 1989. H. pylori IgG and
      IgA antibodies were measured by enzyme-linked immunosorbent assay and
      triglyceride, total cholesterol and high-density lipoprotein cholesterol
      concentrations by routine enzymatic methods. A total of 52% of the subjects were
      positive for both H. pylori specific IgG and IgA and 31% were antibody-negative.
      The serum triglyceride and total cholesterol concentrations were significantly
      higher in the males with positive IgG and IgA antibody titres for H. pylori than
      in the males with no signs of infection (1.20 vs. 1.03 mmol/l, P < 0.001 and 6.59
      vs. 6.11 mmol/l, P < 0.001, respectively). The associations remained
      statistically significant in non-smokers after the adjustment for age, body mass
      index (BMI) and social class. The finding supports the hypothesis that chronic
      infections may modify the serum lipid profile in a way that increases the risk of
      atherosclerosis.

PMID- 9920524
TI  - Angiotensin I-converting enzyme gene polymorphism in a low-risk European
      population for coronary artery disease.
AB  - An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme
      (ACE) has been associated with an increased risk of coronary artery disease (CAD)
      and myocardial infarction (MI). However, this finding has not been fully
      investigated in European populations with very low CAD risk. In a case-control
      study on a population from Southern Europe (Toulouse, France), we evaluated the
      ACE I/D polymorphism in 405 men, aged 35-65 years, who underwent coronary
      angiography and in 357 representative control men within the same age range. We
      also explored associations in the patients between this polymorphism and CAD
      severity. The ACE genotype was not associated with the presence of either CAD or
      MI. The ACE genotype was not a marker for angiographically assessed CAD severity.
      In a sample in one of the European populations with the lowest CAD risk, ACE I/D
      polymorphism was not associated with an increased risk for CAD or MI and did not
      influence the extent of CAD.

PMID- 9920525
TI  - Effects of low density and high density lipoproteins isolated from non-insulin
      dependent diabetic patients on prostaglandin secretion by mouse macrophage cell
      line P388D1.
AB  - We have previously shown that low-density (LDL) and high-density (HDL)
      lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release
      by murine macrophages. In this pilot study, we have measured PG production
      induced by lipoproteins of six diabetic patients with poor metabolic control,
      compared to five healthy controls. Plasma lipoprotein levels were similar in both
      groups. Lipoprotein fractions were purified by sequential ultracentrifugation.
      After lipoprotein incubation with cells, supernatants were extracted and PG
      quantified by HPLC. In presence of LDL, in control subjects, there was an
      increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic
      patients, the secretion pattern was similar. In presence of HDL, in control
      subjects, total PG secretion was also increased, but it was balanced between TxB2
      and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the
      secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l).
      the secretion was balanced between TxB2 and prostacyclin. Comparison of means of
      areas under curve for the two groups studied showed that LDL increased all PG
      secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha),
      while HDL increased all PG secretion in controls compared to diabetic patients,
      except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in
      diabetic patients, which is a major proaggregant and vasoconstrictive agent.
      There was also an increased secretion of all PG in diabetic patients.

PMID- 9920526
TI  - Laser Doppler imaging and capillary microscopy in ischemic ulcers.
AB  - The local distribution of laser Doppler flux (mainly thermoregulatory perfusion)
      and capillary density (nutritive circulation) within 25 ischemic leg ulcers and
      their adjacent skin were investigated. For this purpose the technique of laser
      Doppler imaging and capillary microscopy were applied. In each ulcer a non
      granulation tissue area (NGTA), a granulation tissue area (GTA) and in adjacent
      skin a skin area (SA) were defined. In these areas the average laser Doppler area
      flux (arbitrary units, AU) and the number of capillaries/mm2 were determined for
      each patient. The mean+/-S.D. of laser Doppler area fluxes were: NGTA 1.30+/
      1.93, GTA 2.13+/-1.53 and SA 1.21+/-0.77 AU, respectively. The differences
      between GTA and NGTA or SA was statistically significant (p < 0.001, each) The
      mean+/-S.D. of capillary densities were as follows: NGTA: 0.56+/-2.06, GTA 6.76+/
      8.39 and SA 16.80+/-7.38 capillaries/mm2, respectively. The following differences
      were statistically significant: NGTA versus GTA (p < 0.01) and SA versus NGTA or
      GTA (p < 0.001, each). In conclusion following characteristics of the three areas
      can be described: In NGTA low laser Doppler area flux is combined with very low
      capillary density (ulcer area without healing). In GTA the highest laser Doppler
      area flux of all three areas and an intermediate capillary density (wound
      healing) is found. In SA an intermediate laser Doppler area flux is associated
      with the highest capillary density of all three areas with the healing process
      nearly completed and no granulation tissue.

PMID- 9920527
TI  - Apolipoprotein(a) size polymorphism in young adults with ischemic stroke.
AB  - High serum lipoprotein(a) (Lp(a)) concentration which is largely determined by
      genetic factors, mainly the apolipoprotein(a) (apo(a)) polymorphism, is
      associated with ischemic cerebrovascular disease. The aim of this study was to
      investigate whether apo(a) size was associated with acute ischemic stroke in
      young adults for which causal factors often remain undetermined. Lipid
      parameters, Lp(a) concentration and apo(a) isoform size distribution were
      determined in 90 young patients (37.4+/-8.7 years) with acute cerebral ischemia,
      and compared to those of control subjects with similar age and sex ratio. Apo(a)
      size was expressed as its apparent number of kringle 4 (Kr 4) repeats. Serum
      Lp(a) concentrations were significantly higher in patients than in controls
      (median values: 0.18 vs. 0.07 g/l, P=0.009) and were as expected inversely
      related to the number of kringle 4 repeats in both controls (r2=-0.61, P < 0.001)
      and patients (r2=-0.56, P < 0.001). However there was no difference in the apo(a)
      isoform size distributions between the two groups (median isoform size: 27 vs. 27
      Kr 4, P=0.25). Lp(a) levels were increased as well in patients with size apo(a)
      isoform < or = 22 Kr 4 as in those with isoforms > 25 Kr 4. Multivariate analysis
      showed that apo(a) phenotype did not appear as a risk factor for cerebrovascular
      infarction. Thus, our results indicate that serum Lp(a) was significantly
      increased in young people with ischemic stroke but fail to reveal a role of small
      sized apo(a) isoforms in the occurrence of this event. They suggest that other
      factors, genetic or environmental in nature, than the apo(a) size contribute to
      increase the serum Lp(a) concentrations in these young patients.

PMID- 9920528
TI  - Therapeutic applications of implantable drug delivery systems.
AB  - In the past, drugs were frequently administered orally, as liquids or in powder
      forms. To avoid problems incurred through the utilization of the oral route of
      drug administration, new dosage forms containing the drug(s) were introduced. As
      time progressed, there was a need for delivery systems that could maintain a
      steady release of drug to the specific site of action. Therefore, drug delivery
      systems were developed to optimize the therapeutic properties of drug products
      and render them more safe, effective, and reliable. Implantable drug delivery
      systems (IDDS) are an example of such systems available for therapeutic use. The
      application of currently available implantable drug delivery systems is the main
      focus of this review. IDDS can be classified into three major categories:
      biodegradable or nonbiodegradable implants, implantable pump systems, and the
      newest atypical class of implants. Biodegradable and nonbiodegradable implants
      are available as monolithic systems or reservoir systems. The release kinetics of
      drugs from such systems depend on both the solubility and diffusion coefficient
      of the drug in the polymer, the drug load, as well as the in vivo degradation
      rate of the polymer, especially, in the case of the biodegradable systems.
      Controlled release of drug from the implantable pump is generally achieved
      utilizing the microtechnology of electronic systems and remote-controlled flow
      rate manipulation through the maintenance of a constant pressure difference. The
      third atypical class includes those which have been recently developed such as
      ceramic hydroxyapatite antibiotic systems used in the treatment of bone
      infections, intraocular implants for the treatment of glaucoma, and transurethral
      implants utilized in the treatment of impotence. The major advantages of these
      systems include targeted local delivery of drugs at a constant rate, less drug
      required to treat the disease state, minimization of possible side effects, and
      enhanced efficacy of treatment. Also, these forms of delivery systems are capable
      of protecting drugs which are unstable in vivo and that would normally require a
      frequent dosing intervals. Due to the development of such sustained release
      formulations, it is now possible to administer unstable drugs once a week to once
      a year that in the past required frequent daily dosing. Preliminary studies using
      these systems have shown superior effectiveness over conventional methods of
      treatment. However, one limitation of these newly developed drug delivery systems
      is the fact that their cost-to-benefit ratio (cost/benefit) is too high which
      restricts their use over conventional dosage forms. Hopefully, in the future, new
      implantable systems can be developed at a lower cost, thereby minimizing the cost
      to-benefit ratio and therefore, be used extensively in standard therapeutic
      practice. Some of the most recently discovered implants are in the early
      developmental stages and more rigorous clinical testing is required prior to
      their use in standard practice.

PMID- 9920529
TI  - The micro-plethysmograph: a new device to measure small volume displacements by
      isolated human airway segments.
AB  - For the study of airway responsiveness in vitro, airway segments have important
      advances over strip or spiral preparations. The method to study isobaric
      contraction of segments is not well established. The aim of this work was to
      develop a model to assess the smooth muscle responses in isolated airway segments
      under isobaric conditions. We developed a microplethysmograph with a volume
      measurement range of 10 to 700 microL, a resolution of 0.02-0.4 microL, and a
      drift of 2.6-0.7% of measurement range min(-1) for its most and least sensitive
      setting, respectively. The plethysmograph is able to compensate for the pressure
      changes induced by the volume changes, enabling for true isobaric measurements.
      We show examples of the isobaric contraction and relaxation of isolated human
      airway segments after stimulation of an airway segment by methacholine,
      isoprenaline, or electrical field stimulation. Apart from studying airway
      responses, the micro-plethysmograph is potentially useful to study the
      contractile properties of watertight and hollow structures like blood vessels,
      gut, and ureter. In addition, this device can be used to measure leak or
      diffusion at any transmural pressure.

PMID- 9920531
TI  - A source of false-negative results in clenbuterol analysis in tissues of veal
      calves.
AB  - The possibility of false-negative results in clenbuterol analysis was
      investigated in bovine tissues. An extraction procedure currently in use was
      adapted to process 100 specimens of different tissues each time. Its efficiency
      and accuracy were investigated radiometrically by means of a series of different
      molar concentration of the tritiated drug. In samples not submitted to extensive
      delipidation, unreliability of the analysis was evident. The measurement of
      tissue clenbuterol content, by a competitive ELISA, gave results numerically
      similar to those existing in literature, but with an accuracy high enough to
      minimize the frequency of false-negative results.

PMID- 9920530
TI  - A comparison of rectal and subcutaneous body temperature measurement in the
      common marmoset.
AB  - Two methods of measuring body temperature were compared in common marmosets.
      Subcutaneous temperatures were measured remotely via previously implanted
      subcutaneous microchips (Plexx BV, IPTT-100) prior to measurement of rectal
      temperature using a conventional rectal probe. Marmosets were treated with saline
      or the brain penetrant, 5-HT1A/B/D receptor agonist SKF-99101H (3-(2
      dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate) (0.3-3 mg/kg SC),
      which has previously been shown to induce hypothermia in guinea pigs. Body
      temperature was sampled immediately before drug administration and at 30-min
      intervals thereafter for a period of 2.5 h. SKF-99101H dose-dependently induced
      hypothermia in the common marmoset and there was close agreement between rectal
      and subcutaneous body temperatures, with an average difference in absolute body
      temperature of 0.26+/-0.02 degrees C. The data show that subcutaneously implanted
      microchips provide a simple, reliable measure of body temperature in common
      marmosets which is sensitive to pharmacological intervention, minimizes handling
      induced stress, and is minimally invasive.

PMID- 9920532
TI  - A novel method for detecting the analgesic effect of drugs by quantifying body
      movement after noxious stimulation in neonatal rat.
AB  - We developed a method for quantifying nociceptive struggling in neonatal rats
      induced by bolus, subcutaneous injection of capsaicin (3-3000 ng). The response
      was quantified by using an audio speaker and electrical instruments such as an
      amplifier, a rectifier, and a monostable multivibrator. Using this method, we
      were able to quantify the nociceptive response which appeared immediately after
      injection of capsaicin. The response peaked at 0-1 min, and then decayed during
      next 1-3 min. Furthermore, this method also detected that the magnitude of the
      response increased dose-dependently up to the maximum dose of 3000 ng. In an
      experiment testing the suitability of this method for screening analgesics, it
      was shown that morphine (0.03-0.3 mg/kg, s.c.) inhibited the response dose
      dependently with an ID50 value of 0.089 mg/kg and that the analgesic effect of
      morphine (1 mg/kg, s.c.) was reversed by naloxone (0.03-0.1 mg/kg, s.c.). Thus it
      can be concluded that this method is useful to quantify the capsaicin-induced
      nociceptive response and is suitable for screening analgesics.

PMID- 9920533
TI  - A mouse model to test the in vivo efficacy of chemical chaperones.
AB  - In vitro studies in transfected cells have indicated that chemical chaperones
      including glycerol (0.5-1.2 M) and trimethylamine oxide (TMAO, 50-100 mM) can
      correct defective trafficking of some proteins, including deltaF508 CFTR in
      cystic fibrosis and AQP2 mutants in nephrogenic diabetes insipidus. To develop a
      mouse model to test the efficacy of chemical chaperones in vivo, glycerol and
      TMAO were administered by intraperitoneal (i.p.), subcutaneous (s.c.), and oral
      routes. Glycerol and TMAO assays that utilized 1-5 microL of tail vein blood were
      developed. Administration by the i.p. and s.c. routes gave maximum serum glycerol
      concentrations of approximately 100 mM, levels that were well below the effective
      in vitro concentrations. Single i.p. or s.c. doses of TMAO (7 g/kg, 8% solution
      in water) resulted in serum [TMAO] greater than 50 mM, with a long half-life
      (t1/2 approximately equal to 18-21 h). Sustained high serum and tissue [TMAO] >
      52 mM for 3 days was achieved by s.c. administration of TMAO (7 g/kg) in water
      every 8 h. Although approximately 50% of the mice died with this multiple-dose
      regimen, the remaining mice had nearly normal liver, renal, and pancreatic
      function. A lower dose of TMAO (5 g/kg) given by the s.c. route every 8 h
      resulted in serum [TMAO] concentration of 22 mM, a level that was well tolerated
      by all mice for 72 h. These mice also had high [TMAO] in urine, 400 mM. These
      results demonstrate that potentially therapeutic concentrations of TMAO can be
      sustained in mice in vivo, permitting the testing of chemical chaperones in
      transgenic mouse models of diseases caused by defective protein trafficking.

PMID- 9920535
TI  - A simplified empirical approach to evaluate the dissociation constant of a full
      agonist by the irreversible receptor inactivation method.
AB  - The estimation of the dissociation constant (Ka) of full agonists represents an
      essential tool for the classification of drugs and drug receptors, in functional
      pharmacology. The evaluation of the Ka was a problem until the development of the
      Furchgott's method (irreversible partial receptor inactivation method), which
      surely represents the most used analysis for the evaluation of the agonist Ka in
      experimental protocols on isolated tissues. The Furchgott's method can furnish a
      reliable estimation of the Ka, but it requires a relatively complicated
      manipulation of experimental data. In this article, an alternative approach for
      the evaluation of the Ka is proposed, on the basis of empirical considerations.
      This method, also based on the partial alkylation of a fraction of receptors,
      needs only the knowledge of the location parameters of the concentration-response
      curves and the application of a very simple equation, without any complicated
      intermediate interpolation of the experimental data.

PMID- 9920534
TI  - Characterization of 5-HT1A receptor functional coupling in cells expressing the
      human 5-HT1A receptor as assessed with the cytosensor microphysiometer.
AB  - The functional activity of a series of 5-HT1A receptor ligands has been evaluated
      in a cell line expressing the human 5-HT1A receptor (h5-HT1A x CHO) using the
      agonist-stimulated increase in extracellular acidification rate, measured with
      the microphysiometer, as a functional assay. Both 5-CT and 8-OH-DPAT were potent
      agonists in stimulating an increase in extracellular acidification rate in h5
      HT1A x CHO cells with estimated EC50 values of 1.2 and 7.8 nM, respectively.
      Additionally, these two 5-HT1A receptor agonists elicited a similar maximum
      response. Concentration-dependent agonist activity was also observed in the
      presence of buspirone, ipsapirone, BMY7378, NAN-190 and WAY100135, and each of
      these compounds behaved as partial 5-HT1A receptor agonists. The selective 5-HT1A
      receptor antagonist WAY100635 produced a potent (IC50, 2.3 nM) and complete block
      of the 8-OH-DPAT-stimulated response. An evaluation of the inhibitory activity of
      a series of 5-HT1A receptor antagonists produced the following rank order of
      potency; WAY100635 > LY206130 (IC50, 7.1 nM) > WAY100135 (30.8 nM) > pindolol
      (76.2 nM) > (-)UH-301 (92.8 nM). Parallel studies on the inhibition of forskolin
      stimulated adenylyl cyclase activity in hS-HT1A x CHO cells revealed that agonist
      potencies were generally similar between the two functional assays and were in
      good agreement with the estimated 5-HT1A receptor binding affinities. However,
      the relative efficacies determined for the partial agonists in the cAMP assay
      were substantially greater than those observed with the microphysiometer.
      Finally, antagonists were considerably weaker in the cAMP assay compared with the
      microphysiometer. The evaluation of 5-HT1A ligands using the microphysiometer,
      which represents a very distinct indice of 5-HT1A receptor function compared with
      the cAMP assay, results in a different profile of functional activity.

PMID- 9920536
TI  - Potential benefits of estrogens and progestogens on breast cancer.
AB  - The mammary gland seems to be the only organ that is not fully developed at
      birth. Estrogens stimulate breast tissue via estrogen receptors (ERs). In the
      mammary gland, ER-mediated mechanisms have been shown to regulate: various growth
      factors, such as TGF-alpha and TGF-beta; enzymes, such as cathepsin D and
      plasminogen-activator; proto-oncogenes, such as c-fos, c-myc and HER-2/neu;
      cyclines and other regulatory substances that provide signaling systems for cell
      division and differentiation; other steroid receptors and epidermal growth factor
      receptors. Estrogen target genes contain estrogen-responsive elements. In these
      genes, transcription will be activated through interaction with the estrogen/ER
      protein complex. Subsequent activation of proto-oncogenes provides an explanation
      for the stimulating effect of estrogens on the glandular breast. Progesterone may
      be the key in influencing the risk of breast cancer with the peak of mitotic
      activity in the breast during the luteal phase of the menstrual cycle. On the
      other hand, in human breast cancer cell lines, both proliferation and inhibition
      have been observed with various progestational agents. Relevant biological and
      clinical issues are pregnancy and exposure to exogenous hormones. The intense
      hormonal stimulation of pregnancy (both estrogen and progesterone) has no adverse
      impact on the course of breast cancer. Pregnancy, with its mammogenetic
      differentiation, results in the protection of this organ from carcinogenesis.
      Characterization of specific lobular morphology serves as an indicator of the
      level of differentiation achieved by the organ, and thus provides means to assess
      the risk of the gland undergoing neoplastic transformation when exposed to given
      agents. Sufficient evidence exists to indicate the possibility of a slightly
      increased risk of breast cancer after approximately one decade of postmenopausal
      estrogen use. A review of the epidemiologic studies of postmenopausal hormone
      replacement and the risk of breast cancer fails to provide definitive evidence.
      Recent information derives from observations of cellular proliferation, plasma
      and tissue estradiol and progesterone receptor levels, and the percentage of
      apoptotic epithelial cells in human breast tissue. Several studies suggest that
      short-term, continuous combined HRT does not increase breast cancer recurrence or
      mortality. The participation of sexual hormones in the mammogenetic process
      during pregnancy might serve as an intermediate end point in assessing the
      effectiveness of hormones as chemopreventive agents. Investigations based on
      history, and breast morphology, should enable us to select estrogens and
      progestogens for HRT, and adopt optimal therapeutic regimens.

PMID- 9920537
TI  - The duration of response to norgestimate and ethinyl estradiol in the treatment
      of acne vulgaris.
AB  - OBJECTIVE: This was a postmarketing, retrospective, exploratory analysis to
      investigate the duration of response to a triphasic combination oral
      contraceptive (OC) (Ortho Tri-Cyclen; Ortho-McNeil Pharmaceutical, Raritan, NJ)
      [norgestimate-ethinyl estradiol]) in the treatment of moderate acne vulgaris.
      PROCEDURES: Healthy women with moderate acne vulgaris were enrolled in two 6
      month, multicenter, randomized, double-blind, placebo-controlled clinical trials.
      Subjects received either 3 weeks of active OC treatment (i.e., 0.035 mg ethinyl
      estradiol plus increasing doses of norgestimate [0.180 mg, 0.215 mg, 0.250 mg])
      and 1 week of inactive tablets, or 4 weeks of color-matched placebo tablets.
      RESULTS: A total of 507 subjects were enrolled in the study. Duration of response
      was analyzed in subjects with at least slight improvement in global progress of
      treatment from the earliest cycle showing response (n = 305) and in subjects with
      at least slight improvement at or before cycle 3 (n = 276); the duration of
      response was statistically significant in favor of the norgestimate-ethinyl
      estradiol group in both cases (P < or = .001). The variability of mean percent
      change in lesions was also statistically significantly greater in the placebo
      group than in the OC group for total lesions (P < or = .001) and inflammatory
      lesions (P < or = .001). CONCLUSION: A triphasic combination of norgestimate and
      ethinyl estradiol lengthens the time interval to recurrence of acne lesions.

PMID- 9920538
TI  - The predictive value of double Gn-RH provocation test in unprimed Gn-RH-primed
      and steroid-primed female patients with Kallmann's syndrome.
AB  - OBJECTIVE: To determine the degree of hypophyseal deficiency in Kallmann's
      syndrome, and the effects of Gn-RH priming and HRT. PATIENTS AND METHODS: Seven
      female patients with complete Kallmann's syndrome were subjected to dynamic tests
      (chlorpromazine, TRH and double Gn-RH provocation test) immediately after their
      first admission to the hospital. In five patients the diagnosis was established
      for the first time (unprimed patients), while in the other two cases the
      diagnosis has been established earlier and the patients were already receiving
      hormonal replacement therapy (HRT-primed patients). In the 5 unprimed patients,
      100 microg Gn-RH s.c. were administered daily for 28-32 days and the double Gn-RH
      test was repeated immediately after. RESULTS: The gonadotropic response of the
      unprimed patients in the administration of Gn-RH was insufficient, mainly in the
      second stimulation, with secretory dominance of FSH (ratio LH/FSH <1), while
      after the monthly Gn-RH priming, the gonadotropic response to Gn-RH had improved,
      with a considerable increase in the peak values of plasma FSH and LH after both
      stimulations, and the LH/FSH ratio was reversed to >1. In the two primed
      patients, the gonadotropic response to Gn-RH administration was better in both
      stimulations than that of the unprimed patients. CONCLUSIONS: Both the short-term
      Gn-RH and the long-term HRT priming improve the secretory promptitude of the
      hypophyseal cells for both gonadotropins, while after long-term Gn-RH priming the
      LH-secreting cells are capable of both release and synthesis of the hormone, as
      can be seen by the results of the second stimulation in the Gn-RH primed
      patients. Consequently, for women with Kallmann's syndrome who wish to become
      pregnant, ovulation induction and conception can be achieved sooner and with less
      cost if they are previously primed.

PMID- 9920541
TI  - Erratum: Ortho- and paradeuterium effects in muon-catalyzed fusion

PMID- 9920539
TI  - Impact of baseline cysts at the time of administration of gonadotropin-releasing
      hormone analog for in vitro fertilization.
AB  - OBJECTIVE: To assess the effects of cysts developed prior to the commencement of
      luteal phase gonadotropin-releasing-hormone-agonist (GnRH-a) in IVF cycles.
      DESIGN: Retrospective analysis. SETTING: In vitro fertilization program in a
      tertiary hospital infertility clinic. PATIENTS: Women stimulated for IVF-ET. All
      stimulations were down-regulated with GnRH-a commenced on day 21 in a long
      protocol before gonadotropin stimulation. MAIN OUTCOME MEASURE: Pregnancy rate.
      RESULTS: Twenty-five of 121 cycles had cysts >15 mm (20.6%); these were
      classified as baseline (nonfunctional) (n = 12) or corpus luteum (n = 13) cysts.
      They had significantly longer suppression periods and lower peak estradiol
      levels, and used more gonadotropins during stimulation. Cysts had no impact on
      the number of oocytes collected or fertilization and pregnancy rates. Patients
      with baseline cysts had a greater duration of suppression and required more
      gonadotropin than those with corpus luteum cysts or those without cysts. The
      cycle outcomes were similar between the groups, but baseline cyst formation is
      likely to increase the cost of IVF. CONCLUSION: These findings suggest that
      baseline cyst formation causes longer suppression duration and greater
      gonadotropin utilization, although an impact on pregnancy rates is unlikely.

PMID- 9920542
TI  - Erratum: Generalized Bogoliubov hypothesis for dense fluids

PMID- 9920540
TI  - Changes in symptoms, blood pressure, glucose, hormones, and lipid levels
      according to weight and body fat distribution in climacteric women.
AB  - OBJECTIVE: To evaluate how symptoms, blood pressure, glucose, hormones and lipid
      levels are modified in climacteric women according to obesity and body fat
      distribution. METHODS: One hundred and thirteen women were studied and divided
      initially according to body mass index (BMI), and afterward to waist-hip ratio
      (WHR). Climacteric symptoms, blood pressure, fasting and post-breakfast glucose,
      hormone and lipid levels were analyzed. Statistical analysis was done by the chi
      square and Mann-Whitney U tests, and the relation of BMI and WHR with several
      variables was assessed by linear regression analysis. RESULTS: When dividing
      patients according to BMI, the only differences were found in age, number of
      diabetic and hypertensive patients, and values of systolic and diastolic blood
      pressure, which were greater in the obese group. When dividing according to WHR
      it was found that high-density lipoproteins were lower in those with upper
      segment body fat distribution. Subgroup analysis showed that chronic diseases are
      frequently found in obese women, while android body fat distribution has an
      additive effect on obesity in some of these variables. CONCLUSION: Chronic
      diseases are more frequently found in obese women, but most of the metabolic
      alterations are modified by body fat distribution in the upper segment.

PMID- 9920543
TI  - Erratum: Reply to "Comment on 'Theory of collective resonance fluorescence in
      strong driving field"'

PMID- 9920544
TI  - Erratum: Geometrical effect on the measurement of stopping power: Angle-dependent
      energy-loss of 7-MeV protons in Cu foils and computer simulation

PMID- 9920545
TI  - Erratum: Free-energy density functional for hard spheres

PMID- 9920546
TI  - Erratum: Ab initio calculations of low-energy electron scattering by HCN
      molecules

PMID- 9920547
TI  - Erratum: Triple-differential cross sections for the fast-electron-impact
      ionization of atomic hydrogen

PMID- 9920548
TI  - Erratum: Efimov states in 4He trimers by two-body effective-range and scattering
      length analysis: A comparison with Faddeev calculations

PMID- 9920550
TI  - Erratum: Small-signal amplification in bifurcating dynamical systems

PMID- 9920549
TI  - Erratum: Two-photon free-free transitions in a Coulomb potential

PMID- 9920551
TI  - Erratum: Macroscopic dynamics near the nematic-columnar transition in liquid
      crystals

PMID- 9920552
TI  - Erratum: Computer simulation of close random packing of equal spheres

PMID- 9920553
TI  - Erratum: Electromagnetic drift modes in an inhomogeneous electron gas

PMID- 9920555
TI  - Erratum: Chaos and incoherence in a model of multiple-photon excitation of
      molecular vibrations

PMID- 9920554
TI  - Erratum: Ab initio calculations of low-energy electron scattering by HCN
      molecules

PMID- 9920556
TI  - Erratum: Resolved nuclear hyperfine structure of a muonated free radical using
      level-crossing spectroscopy

PMID- 9920558
TI  - Erratum: Flow patterns and nonlinear behavior of traveling waves in a convective
      binary fluid

PMID- 9920557
TI  - Erratum: New method for the solution of the logarithmic nonlinear Schrodinger
      equation via stochastic mechanics

PMID- 9920559
TI  - Erratum: Time-dependent local-density theory of dielectric effects in small
      molecules

PMID- 9920560
TI  - Erratum: Calculation of total inelastic-x-ray-scattering cross sections (d sigma
      /d Omega )inel

PMID- 9920561
TI  - Erratum: Electron-impact excitation of the resonance transition in Be+: An ab
      initio treatment of core-correlation and -polarization effects

PMID- 9920563
TI  - Erratum: Selection rules for vibrational energy loss by resonant electron impact
      in polyatomic molecules

PMID- 9920562
TI  - Erratum: Hypervirial 1/N expansion for the bound-state energy spectrum of the
      generalized exponential-cosine-screened Coulomb potential

PMID- 9920565
TI  - Erratum: Interference effects on the H(2p) to H(2s) branching ratio in the
      photodissociation of hydrogen and deuterium

PMID- 9920564
TI  - Erratum: Plasma screening effects on proton-impact excitation of positive ions

PMID- 9920566
TI  - Erratum: Convection in binary mixtures: A Galerkin model with impermeable
      boundary conditions

PMID- 9920567
TI  - Erratum: Intense molecular emissions in the region of 431 nm in long-pulsed,
      electron-beam-generated helium plasmas and afterglows

PMID- 9920568
TI  - Erratum: Exact matrix elements of the Uehling potential in a basis of explicitly
      correlated two-particle functions

PMID- 9920570
TI  - Erratum: Equilibrium polymerization of chains and rings: A bicritical phenomenon

PMID- 9920569
TI  - Erratum: Fourier transform of the product of N one-center hydrogenic orbitals

PMID- 9920571
TI  - Erratum: Excitation of the 1s5 and 1s4 levels of neon by low-energy electrons

PMID- 9920572
TI  - Erratum: ac Stark splitting in multiphoton excitation of atomic hydrogen in
      flames: Abnormal peak asymmetry due to pressure broadening

PMID- 9920573
TI  - Erratum: Electron-noble-gas spin-flip scattering at low energy

PMID- 9920574
TI  - Erratum: Transition probabilities in neutral barium

PMID- 9920575
TI  - Erratum: Density matrices of the excited H(n=2 and 3) atoms formed in 25-100-keV
      proton-helium charge-transfer collisions

PMID- 9920576
TI  - Erratum: Use of Dirichlet boundary conditions for electron-atom scattering

PMID- 9920577
TI  - Erratum: Discrepancy between theory and experiment for noncoplanar symmetric
      (e,2e) momentum profiles of H2(1 Sigma g+)

PMID- 9920579
TI  - Erratum: Balancing the Schrodinger equation with Davydov (IBAnsatzeP

PMID- 9920578
TI  - Erratum: Perturbation approximations for scattering amplitudes in ion-atom
      collisions

PMID- 9920580
TI  - Erratum: X-ray parametric scattering from atomic K-shell electrons

PMID- 9920581
TI  - Erratum: Role of excited states in multiphoton dynamics

PMID- 9920582
TI  - Erratum: e+/--CO and e+/--CO2 total cross-section measurements

PMID- 9920583
TI  - Erratum: Laser-induced autoionizinglike behavior, population trapping, and
      stimulated Raman processes in real atoms

PMID- 9920584
TI  - Erratum: High-accuracy calculation of muonic molecules using random-tempered
      basis sets

PMID- 9920585
TI  - Erratum: Madelung energy of a one-dimensional Coulomb lattice

PMID- 9920586
TI  - Erratum: Geometries of muonic molecular ions

PMID- 9920587
TI  - Erratum: Laser-induced fluorescence from low-lying Sigma and Pi states of the
      HgZn excimer

PMID- 9920588
TI  - Erratum: 1/f noise in the radioactive beta - decay of 204Tl

PMID- 9920589
TI  - Erratum: Nonlinear transport processes and fluid dynamics: Cylindrical Couette
      flow of Lennard-Jones fluids

PMID- 9920590
TI  - Erratum: Dynamical interaction of an atomic oscillator with squeezed radiation
      inside a cavity

PMID- 9920591
TI  - Erratum: Velocity-dependent fluctuations: Breaking the randomness of Brownian
      motion

PMID- 9920592
TI  - Erratum: Quantum behavior of a two-level atom interacting with two modes of light
      in a cavity

PMID- 9920594
TI  - Erratum: Theory of a two-photon squeezed laserlike oscillator

PMID- 9920593
TI  - Erratum: Amplitude noise reduction in atomic and semiconductor lasers

PMID- 9920596
TI  - Erratum: Spatial and temporal behavior of pattern formations and defect motions
      in the electrohydrodynamic instability of nematic liquid crystals

PMID- 9920595
TI  - Erratum: Raman gain suppression with multimode lasers

PMID- 9920597
TI  - Erratum: Equilibrium statistical thermodynamics of a many-particle system coupled
      to an external scalar field

PMID- 9920599
TI  - Erratum: "Expectation values of rP for arbitrary hydrogenic states"

PMID- 9920598
TI  - Erratum: dc-field-coupled autoionizing states for laser action without population
      inversion

PMID- 9920601
TI  - Erratum: Strong-field theory of four-wave mixing. II. Density-matrix treatment of
      extra resonances

PMID- 9920600
TI  - Erratum: Wigner symbols, quantum dynamics, and the kicked rotator

PMID- 9920602
TI  - Erratum: Finite atomic lifetime behavior of micromasers

PMID- 9920603
TI  - Erratum: Atomic-charge convexity and the electron density at the nucleus

PMID- 9920604
TI  - Erratum: Helium momentum-space wave function and Compton profile

PMID- 9920605
TI  - Erratum: Photoionization cross section of hydrogenic atoms: A generating function
      solution

PMID- 9920606
TI  - Erratum: Analytic structure of the ac quasienergy in the complex field plane

PMID- 9920608
TI  - Erratum: Oscillatory instability of deep cells in directional solidification

PMID- 9920607
TI  - Erratum: "Compatibility of the cosine and sine operators"

PMID- 9920609
TI  - Erratum: Resonant periodic-gain surface-emitting semiconductor lasers and
      correlated emission in a ring cavity

PMID- 9920610
TI  - Erratum: Excitation by fast atoms at very high electric field to gas-density
      ratios in argon

PMID- 9920611
TI  - Erratum: Drift, shape, and intrinsic destabilization of pulses of traveling-wave
      convection

PMID- 9920613
TI  - Erratum: Semiclassical chaos in quartic anharmonic oscillators

PMID- 9920612
TI  - Erratum: Semiclassical chaos, the uncertainty principle, and quantum dissipation

PMID- 9920614
TI  - Erratum: Schrodinger equation for two-electron atoms expressed in terms of
      symmetric sparse matrices involving only O(4,2) representations

PMID- 9920615
TI  - Erratum: Radiation trapping in a stepwise-excitation electron-laser coincidence
      experiment

PMID- 9920616
TI  - Erratum: Simple formula for the cross sections of resonant charge transfer
      between atoms and their positive ions at low impact velocity

PMID- 9920618
TI  - Erratum: Two-photon ionization of atomic hydrogen with elliptically polarized
      light

PMID- 9920617
TI  - Erratum: Solutions of the telegrapher's equation in the presence of traps

PMID- 9920619
TI  - Erratum: Semiclassical approximation of cross sections with many rainbow peaks

PMID- 9920620
TI  - Erratum: Angular distribution of electrons elastically scattered from water vapor

PMID- 9920621
TI  - Erratum: Multiphoton ionization in superintense, high-frequency laser fields. II.
      Stabilization of atomic hydrogen in linearly polarized fields

PMID- 9920622
TI  - Erratum: Asymmetric-top description of Rydberg-electron dynamics in crossed
      external fields

PMID- 9920623
TI  - Erratum: Variational calculation for the ground state of lithium and QED
      corrections for Li-like ions

PMID- 9920624
TI  - Erratum: Quantum tunneling in dissipative systems

PMID- 9920625
TI  - Erratum: Near-dipole-dipole effects in dense media: Generalized Maxwell-Bloch
      equations

PMID- 9920627
TI  - Erratum: Experimental consequences of Einstein-Podolsky-Rosen-Bohm-Bell gedanken
      experiment

PMID- 9920626
TI  - Erratum: Variational close-coupling calculation for positron-hydrogen scattering
      at low energies

PMID- 9920628
TI  - Erratum: Double-well dynamics of two ions in the Paul and Penning traps

PMID- 9920630
TI  - Erratum: Relation between the electron scattering length and the van der Waals
      approximation to the equation of state

PMID- 9920629
TI  - Erratum: Roothaan-Hartree-Fock wave functions for atoms from Cs through U

PMID- 9920632
TI  - Erratum: Equations satisfied by the kinetic-energy functional and its derivatives

PMID- 9920631
TI  - Erratum: Quantum projection noise: Population fluctuations in two-level systems

PMID- 9920633
TI  - Erratum: Geometric phase with photon statistics and squeezed light for the
      dispersive fiber

PMID- 9920635
TI  - Erratum: Quantum nonlocality in a delayed-choice experiment with partial,
      controllable memory erasing

PMID- 9920634
TI  - Erratum: Correlated Keldysh-Faisal-Reiss theory of above-threshold double
      ionization of He in intense laser fields

PMID- 9920636
TI  - Erratum: Retardation (or Casimir) potential for the Rydberg hydrogen molecule

PMID- 9920637
TI  - Erratum: Dipole coupling of atoms and light in gravitational fields

PMID- 9920639
TI  - Erratum: Charge exchange and excittion in H+He2+ and He++H+ collisions using
      single- and multichannel perturbed-stationary-state propagators

PMID- 9920638
TI  - Erratum: Effective core polarizabilities in Ba high-l Nsnl double Rydberg atoms

PMID- 9920640
TI  - Erratum: Ionization of Rydberg hydrogen by a half-cycle pulse

PMID- 9920642
TI  - Erratum: Distribution of electrons in double photoionization of helium and
      heavier atoms in the asymptotic region

PMID- 9920641
TI  - Erratum: Measurement of the Bell operator and quantum teleportation

PMID- 9920644
TI  - Erratum: Universal superpositions of coherent states and self-similar potentials

PMID- 9920643
TI  - Erratum: Two-ion superradiance theory

PMID- 9920645
TI  - Erratum: Accurate variational calculations of energies of the 2 2S, 2 2P, and 3
      2D states and the dipole, quadrupole, and dipole-quadrupole polarizabilities and
      hyperpolarizability of the lithium atom

PMID- 9920647
TI  - Erratum: Transverse-mode selection in single-longitudinal-mode lasers

PMID- 9920646
TI  - Erratum: Isotopic effect of the mean lifetimes of the NeAr2+ doubly charged rare
      gas dimer

PMID- 9920648
TI  - Erratum: Landau-Zener model: Effects of finite coupling duration

PMID- 9920649
TI  - Erratum: Band gaps for atoms in light-based waveguides

PMID- 9920650
TI  - Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an
      intracellular determinant of glycine receptor channel gating.
AB  - Missense mutations as well as a null allele of the human glycine receptor alpha1
      subunit gene GLRA1 result in the neurological disorder hyperekplexia [startle
      disease, stiff baby syndrome, Mendelian Inheritance in Man (MIM) #149400]. In a
      pedigree showing dominant transmission of hyperekplexia, we identified a novel
      point mutation C1128A of GLRA1. This mutation encodes an amino acid substitution
      (P250T) in the cytoplasmic loop linking transmembrane regions M1 and M2 of the
      mature alpha1 polypeptide. After recombinant expression, homomeric alpha1(P250T)
      subunit channels showed a strong reduction of maximum whole-cell chloride
      currents and an altered desensitization, consistent with a prolonged recovery
      from desensitization. Apparent glycine binding was less affected, yielding an
      approximately fivefold increase in Ki values. Topological analysis predicts that
      the substitution of proline 250 leads to the loss of an angular polypeptide
      structure, thereby destabilizing open channel conformations. Thus, the novel
      GLRA1 mutant allele P250T defines an intracellular determinant of glycine
      receptor channel gating.

PMID- 9920652
TI  - G-proteins are involved in 5-HT receptor-mediated modulation of N- and P/Q- but
      not T-type Ca2+ channels.
AB  - 5-HT produces voltage-independent inhibition of the N-, P/Q-, and T-type Ca2+
      currents in sensory neurons of Xenopus larvae by acting on 5-HT1A and 5-HT1D
      receptors. We have explored the underlying mechanisms further and found that the
      inhibition of high voltage-activated (HVA) currents by 5-HT is mediated by a
      pertussis toxin-sensitive G-protein that activates a diffusible second messenger.
      Although modulation of T-type currents is membrane-delimited, it was not affected
      by GDP-beta-S (2 mM), GTP-gamma-S (200 microM), 5'-guanylyl-imidodiphosphate
      tetralithium (200 microM), aluminum fluoride (AlF4-, 100 microM), or pertussis
      toxin, suggesting that a GTP-insensitive pathway was involved. To investigate the
      modulation of the T currents further, we synthesized peptides that were derived
      from conserved cytoplasmic regions of the rat 5-HT1A and 5-HT1D receptors.
      Although two peptides derived from the third cytoplasmic loop inhibited the HVA
      currents by activating G-proteins and occluded the modulation of HVA currents by
      5-HT, two peptides from the second cytoplasmic loop and the C tail had no effect.
      None of the four receptor-derived peptides had any effect on the T-type currents.
      We conclude that 5-HT modulates T-type channels by a membrane-delimited pathway
      that does not involve G-proteins and is mediated by a functional domain of the
      receptor that is distinct from that which couples to G-proteins.

PMID- 9920651
TI  - Blockade of tetrahydrobiopterin synthesis protects neurons after transient
      forebrain ischemia in rat: a novel role for the cofactor.
AB  - The generation of nitric oxide (NO) aggravates neuronal injury. (6R)-5,6,7,8
      Tetrahydro-L-biopterin (BH4) is an essential cofactor in the synthesis of NO by
      nitric oxide synthase (NOS). We attempted to attenuate neuron degeneration by
      blocking the synthesis of the cofactor BH4 using N-acetyl-3-O-methyldopamine
      (NAMDA). In vitro data demonstrate that NAMDA inhibited GTP cyclohydrolase I, the
      rate-limiting enzyme for BH4 biosynthesis, and reduced nitrite accumulation, an
      oxidative metabolite of NO, without directly inhibiting NOS activity. Animals
      exposed to transient forebrain ischemia and treated with NAMDA demonstrated
      marked reductions in ischemia-induced BH4 levels, NADPH-diaphorase activity, and
      caspase-3 gene expression in the CA1 hippocampus. Moreover, delayed neuronal
      injury in the CA1 hippocampal region was significantly attenuated by NAMDA. For
      the first time, these data demonstrate that a cofactor, BH4, plays a significant
      role in the generation of ischemic neuronal death, and that blockade of BH4
      biosynthesis may provide novel strategies for neuroprotection.

PMID- 9920653
TI  - Ca2+-induced deprotonation of peptide hormones inside secretory vesicles in
      preparation for release.
AB  - The acidic environment inside secretory vesicles ensures that neuropeptides and
      peptide hormones are packaged in a concentrated condensed form. Although this is
      optimal for storage, decondensation limits release. Thus, it would be
      advantageous to alter the physical state of peptides in preparation for
      exocytosis. Here, we report that depolarization of the plasma membrane rapidly
      increases enhanced green fluorescent protein (EGFP)-tagged hormone fluorescence
      inside secretory vesicles. This effect requires Ca2+ influx and persists when
      exocytosis is inhibited by N-ethylmaleimide. Peptide deprotonation appears to
      produce this response, because it is not seen when the vesicle pH gradient is
      collapsed or when a pH-insensitive GFP variant is used. These data demonstrate
      that Ca2+ evokes alkalinization of the inside of secretory vesicles before
      exocytosis. Thus, Ca2+ influx into the cytoplasm alters the physical state of
      intravesicular contents in preparation for release.

PMID- 9920654
TI  - Differential modulation of synaptic transmission by calcium chelators in young
      and aged hippocampal CA1 neurons: evidence for altered calcium homeostasis in
      aging.
AB  - The effects of membrane-permeant Ca2+ chelators on field EPSPs (fEPSPs) were
      measured in the hippocampal CA1 region of brain slices from young (2-4 months)
      and old (24-27 months) Fischer 344 rats. BAPTA-AM depressed fEPSPs in young
      slices by up to 70% but enhanced fEPSPs by 30% in aged slices. EGTA-AM, with
      slower binding kinetics, did not affect fEPSPs from young slices but enhanced
      fEPSPs in aged slices. BAPTA derivatives with calcium dissociation constants (Kd)
      of 0.2-3.5 microM reduced or enhanced fEPSPs in young and aged slices,
      respectively, but 5',5'-dinitro BAPTA-AM (Kd of approximately 7000 microM) had no
      effect. Frequency facilitation of the fEPSPs occurred in young, but not in aged,
      slices, except when BAPTA-AM or EGTA-AM was perfused onto aged slices. The
      differential effects of BAPTA-AM in young and old slices were eliminated by
      perfusing with a low Ca2+-high Mg2+ saline or with the calcium blocker Co2+.
      These data suggest that intracellular Ca2+ regulation is altered and raised in
      aged neurons. Cell-permeant calcium buffers may be able to "ameliorate" deficits
      in synaptic transmission in the aged brain.

PMID- 9920655
TI  - Lectin-induced inhibition of desensitization of the kainate receptor GluR6
      depends on the activation state and can be mediated by a single native or ectopic
      N-linked carbohydrate side chain.
AB  - The ionotropic glutamate receptor GluR6 exhibits strongly and rapidly
      desensitizing current responses. Treatment of heterologically expressed GluR6
      with the lectin concanavalin A (ConA) in Xenopus oocytes as well as in human
      embryonic kidney-293 cells results in a considerable increase of the steady-state
      current, presumably by inhibiting receptor desensitization. In the present study,
      we investigated the molecular basis of this effect using a systematic mutagenesis
      approach. We found that although N-glycosylation is an absolute prerequisite for
      the lectin-mediated inhibition of desensitization, no single one of the nine
      extracellular consensus sites for N-glycosylation of GluR6 is required. Rather,
      each of the nine N-linked carbohydrate side chains is independently capable of
      modulatory interaction with the lectin. Moreover, even artificially introduced N
      glycosylation sites can substitute for native sites. Thus, the specific site of
      the lectin binding does not appear to be important for its desensitization
      inhibiting action. Furthermore, we show that the extent of the receptor's ConA
      sensitivity depends on its state of activation, because the desensitized GluR6
      exhibits significantly lower lectin sensitivity than the nondesensitized
      receptor. We conclude that binding of ConA "locks" the receptor in the
      activatable state, thereby inhibiting conformational changes required to shift
      the receptor to the desensitized state.

PMID- 9920656
TI  - Identification of microglial signal transduction pathways mediating a neurotoxic
      response to amyloidogenic fragments of beta-amyloid and prion proteins.
AB  - Microglial interaction with amyloid fibrils in the brains of Alzheimer's and
      prion disease patients results in the inflammatory activation of these cells. We
      observed that primary microglial cultures and the THP-1 monocytic cell line are
      stimulated by fibrillar beta-amyloid and prion peptides to activate identical
      tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine
      kinases Lyn and Syk are activated by the fibrillar peptides and initiate a
      signaling cascade resulting in a transient release of intracellular calcium that
      results in the activation of classical PKC and the recently described calcium
      sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2
      follows as a subsequent downstream signaling event. We demonstrate that PYK2 is
      positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate
      required for ERK activation. Importantly, the signaling response elicited by beta
      amyloid and prion fibrils leads to the production of neurotoxic products. We have
      demonstrated in a tissue culture model that conditioned media from beta-amyloid-
      and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse
      cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with
      specific enzyme inhibitors that target various components of the signal
      transduction pathway linked to the inflammatory responses.

PMID- 9920657
TI  - Prostaglandin E2 stimulates amyloid precursor protein gene expression: inhibition
      by immunosuppressants.
AB  - Amyloid plaques that accumulate in the brains of patients with Alzheimer's
      disease (AD) are primarily composed of aggregates of amyloid peptides that are
      derived from the amyloid precursor protein (APP). Overexpression of APP in cell
      cultures increases the formation of amyloidogenic peptides and causes
      neurodegeneration and cognitive dysfunction in transgenic mice. We now report
      that activation of prostaglandin E2 (PGE2) receptors increases cAMP formation and
      stimulates overexpression of APP mRNA and holoprotein in primary cultures of
      cortical astrocytes. Levels of glial fibrillary acidic protein were also
      increased by PGE2 treatment, suggesting that these cultured astrocytes resemble
      reactive astrocytes found in vivo. The stimulation by PGE2 of APP synthesis was
      mimicked or blocked by activators or inhibitors, respectively, of protein kinase
      A. Actinomycin D or cycloheximide also inhibited the increase in APP holoprotein
      stimulated by PGE2. Treatment of astrocytes with 8-Bromo-cAMP or forskolin for 24
      hr also stimulated APP overexpression in cultured astrocytes. The
      immunosuppressants cyclosporin A and FK-506 inhibited the increase in APP mRNA
      and holoprotein levels caused by PGE2 or by other treatments that elevated
      cellular cAMP levels; the inhibitory effect of FK-506 but not of cyclosporin A
      was attenuated by rapamycin. These results suggest that prostaglandins produced
      by brain injury or inflammation can activate APP transcription in astrocytes and
      that immunosuppressants may be used to prevent APP overexpression and possibly
      the pathophysiological processes underlying AD.

PMID- 9920658
TI  - Functional properties of two bombesin-like peptide receptors revealed by the
      analysis of mice lacking neuromedin B receptor.
AB  - The neuromedin B-preferring receptor (NMB-R) is one of the members of the
      bombesin (BN)-like peptide receptor subfamily in mammals. Previously, we have
      generated and characterized mice with targeted disruption of the two other BN
      like peptide receptors, bombesin receptor subtype-3 (BRS-3) and gastrin-releasing
      peptide-preferring receptor (GRP-R). Here we describe the generation and analysis
      of NMB-R-deficient mice to investigate how NMB-R differs from BRS-3 and GRP-R.
      Compensation for NMB-R deficiency by overexpression of GRP-R and/or BRS-3 was not
      detected. Although the hypothermic effect of NMB was reduced by 50% in NMB-R
      deficient mice, the effect of GRP infusion was comparable to the wild-type mice.
      In contrast, fundic smooth muscle contraction on stimulation with NMB or GRP was
      normal in NMB-R-deficient mice. Administration of GRP but not NMB suppressed
      glucose intake in both normal and NMB-R-deficient mice. These results suggest
      that the NMB-R has an essential role in thermoregulation, but not for smooth
      muscle contraction of the fundus or for the suppression of feeding behavior. In
      addition, the behavioral phenotypes of GRP-R-deficient mice were not observed in
      NMB-R-deficient mice. These data show that the functions of NMB-R and GRP-R are
      distinct, with only partial overlap.

PMID- 9920659
TI  - Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear
      response and conditioned taste aversion.
AB  - Metabotropic glutamate receptors (mGluRs) consist of eight different subtypes and
      exert their effects on second messengers and ion channels via G-proteins. The
      function of individual mGluR subtypes in the CNS, however, largely remains to be
      clarified. We examined the fear response of freezing after electric shock in wild
      type and mGluR7(-/-) knockout littermates. Wild-type mice displayed freezing
      immediately after and 1 d after footshock. In comparison, mGluR7(-/-) knockout
      mice showed significantly reduced levels in both immediate postshock and delayed
      freezing responses. However, the knockout mice exhibited no abnormalities in pain
      sensitivity and locomotor activity. To further examine amygdala-dependent
      behavior, we performed conditioned taste aversion (CTA) experiments. In wild-type
      mice, the administration of saccharin followed by intraperitoneal injection of
      the malaise-inducing agent LiCl resulted in an association between saccharin and
      LiCl. This association caused strong CTA toward saccharin. In contrast, mGluR7(-/
      ) knockout mice failed to associate between the taste and the negative reinforcer
      in CTA experiments. Again, the knockout mice showed no abnormalities in taste
      preference and in the sensitivity to LiCl toxicity. These results indicate that
      mGluR7 deficiency causes an impairment of two distinct amygdala-dependent
      behavioral paradigms. Immunohistochemical and immunoelectron-microscopic analyses
      showed that mGluR7 is highly expressed in amygdala and preferentially localized
      at the presynaptic axon terminals of glutamatergic neurons. Together, these
      findings strongly suggest that mGluR7 is involved in neural processes subserving
      amygdala-dependent averse responses.

PMID- 9920660
TI  - Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion
      formation and neuronal survival by caspase inhibition.
AB  - Neuronal intranuclear inclusions are found in the brains of patients with
      Huntington's disease and form from the polyglutamine-expanded N-terminal region
      of mutant huntingtin. To explore the properties of inclusions and their
      involvement in cell death, mouse clonal striatal cells were transiently
      transfected with truncated and full-length human wild-type and mutant huntingtin
      cDNAs. Both normal and mutant proteins localized in the cytoplasm, and
      infrequently, in dispersed and perinuclear vacuoles. Only mutant huntingtin
      formed nuclear and cytoplasmic inclusions, which increased with polyglutamine
      expansion and with time after transfection. Nuclear inclusions contained
      primarily cleaved N-terminal products, whereas cytoplasmic inclusions contained
      cleaved and larger intact proteins. Cells with wild-type or mutant protein had
      distinct apoptotic features (membrane blebbing, shrinkage, cellular
      fragmentation), but those with mutant huntingtin generated the most cell
      fragments (apoptotic bodies). The caspase inhibitor Z-VAD-FMK significantly
      increased cell survival but did not diminish nuclear and cytoplasmic inclusions.
      In contrast, Z-DEVD-FMK significantly reduced nuclear and cytoplasmic inclusions
      but did not increase survival. A series of N-terminal products was formed from
      truncated normal and mutant proteins and from full-length mutant huntingtin but
      not from full-length wild-type huntingtin. One prominent N-terminal product was
      blocked by Z-VAD-FMK. In summary, the formation of inclusions in clonal striatal
      cells corresponds to that seen in the HD brain and is separable from events that
      regulate cell death. N-terminal cleavage may be linked to mutant huntingtin's
      role in cell death.

PMID- 9920661
TI  - Protein kinase C modulation of recombinant NMDA receptor currents: roles for the
      C-terminal C1 exon and calcium ions.
AB  - Protein kinase C (PKC) positively modulates NMDA receptor (NMDAR) currents. In
      contrast to previous reports, this study determines the importance of individual
      exons in the mechanism underlying the potentiation process by examining the
      complete set of eight naturally occurring splice variants expressed in Xenopus
      oocytes both as homomers and as heteromeric NR1/NR2A or NR1/NR2B complexes. After
      PKC stimulation, homomeric currents demonstrated a high level of potentiation (
      approximately 500% of untreated baseline currents) that reduced to a lower level
      ( approximately 300% of baseline) in variants containing the first C-terminal
      exon (C1). An ANOVA showed that only C1 and no other exon or interaction of exons
      determined the degree of NMDAR current modulation by PKC. When recordings were
      performed in solutions in which barium replaces calcium, only the lower form of
      potentiation was observed, regardless of the splice variant exon composition.
      This suggested an important role for calcium in the PKC modulation of homomeric
      NMDA splice variant currents in which the C1 exon also participates. The
      effectiveness of the C1 exon to reduce the higher form of potentiation is
      modulated by heteromeric assemblies with NR2A heteromers yielding smaller levels
      of potentiation and a larger C1 exon effect compared with NR2B heteromers. The
      heteromers demonstrated the higher form of potentiation even in the absence of
      calcium. Furthermore, calcium had different effects in the potentiation of the
      heteromers depending on the NR2 subunit. This study refines the region of the NR1
      subunit involved in a modulation crucial to the function of NMDA receptors and
      provides evidence that the NR2A and NR2B subunits realize this modulation
      differentially.

PMID- 9920662
TI  - The 69 bp circadian regulatory sequence (CRS) mediates per-like developmental,
      spatial, and circadian expression and behavioral rescue in Drosophila.
AB  - The period (per) gene is an essential component of the circadian timekeeping
      mechanism in Drosophila. This gene is expressed in a circadian manner, giving
      rise to a protein that feeds-back to regulate its own transcription. A 69 bp
      clock regulatory sequence (CRS) has been identified previously upstream of the
      period gene. The CRS confers wild-type mRNA cycling when used to drive a lacZ
      reporter gene in transgenic flies. To determine whether the CRS also mediates
      proper developmental and spatial expression and behavioral rescue, we used the
      CRS to drive either lacZ or per in transgenic flies. The results show that the
      CRS is able to activate expression in pacemaker neuron precursors in larvae and
      essentially all tissues that normally express per in pupae and adults. The CRS is
      sufficient to rescue circadian feedback loop function and behavioral rhythms in
      per01 flies. However, the period of locomotor activity rhythms shortens if a
      stronger basal promoter is used. This study shows that regulatory elements
      sufficient for clock-dependent and tissue-specific per expression in larvae,
      pupae, and adults are present in the CRS and that the period of adult locomotor
      activity rhythms is dependent, in part, on the overall level of per transcripts.

PMID- 9920663
TI  - Expression of a novel protocadherin, OL-protocadherin, in a subset of functional
      systems of the developing mouse brain.
AB  - We cloned a novel protocadherin cDNA, which we named OL-protocadherin (OL-pc),
      from mouse brain cDNA libraries. Its cytoplasmic region showed no similarities to
      other protocadherins, indicating that it belongs to a novel subfamily of
      protocadherins. Experiments using transfectants showed that OL-pc is a homophilic
      cell-cell adhesion molecule. The molecular mass of OL-pc was 140 kDa in the
      brain. Expression of OL-pc mRNA was specific to the nervous system, changing over
      time from the embryonic stage to the adult stage. The OL-pc expression seemed to
      be restricted to a subset of functionally related brain nuclei and regions such
      as the nuclei in the main olfactory system, the limbic system, and the
      olivocortical projection. There were at least two distinct patterns of
      distribution for the OL-pc protein. First, it was localized in particular brain
      nuclei or compartments, such as the stripes of the developing cerebellum. Second,
      it was found at the synapse in regions such as the glomeruli of the olfactory
      bulb. In addition, the OL-pc protein seemed not to be detected or was detected
      only weakly in some regions, such as hippocampus in which the mRNA was expressed
      at high levels. These results indicate that the expression of OL-pc is
      developmentally regulated in a subset of the functional systems and that it may
      be involved in the formation of the neural network by segregation of the brain
      nuclei and mediation of the axonal connections.

PMID- 9920664
TI  - Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in
      dopaminergic neurons of the substantia nigra.
AB  - G-protein-gated K+ (KG) channels generate slow inhibitory postsynaptic potentials
      in the brain. Current opinion suggests that neuronal KG channels are
      heterotetramers of Kir3.1 and Kir3.2. In substantia nigra (SN), however, mRNA of
      Kir3.1 does not express, whereas that of Kir3.2 clearly does. Therefore, we have
      characterized the KG channels containing Kir3.2 subunits in SN using biochemical
      and immunological techniques. We found that they were composed of only Kir3.2
      subunits and did not contain significant amounts of either Kir3.1 or Kir3.3.
      Furthermore, at least some of the KG channels in SN were assemblies of the
      splicing variants Kir3. 2a and Kir3.2c. The channels were localized specifically
      at the postsynaptic membrane on the dendrites of dopaminergic neurons. Kir3. 2c,
      but not Kir3.2a, could bind a PDZ domain-containing protein, PSD-95. The
      heterologously expressed KG channels composed of Kir3.2a plus Kir3.2c or Kir3.2a
      alone were activated by G-protein stimulation, but expression of Kir3.2c alone
      was not. This study reveals that the Kir3.2 splicing variants play distinct roles
      in the control of function and localization of some of the KG channels in
      dopaminergic neurons of SN.

PMID- 9920666
TI  - The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate
      photoreceptors.
AB  - Kinesin motors are presumed to transport various membrane compartments within
      neurons, but their specific in vivo functions, cargoes, and expression patterns
      in the brain are unclear. We have investigated the distribution of KIF3A, a
      member of the heteromeric family of kinesins, in the vertebrate retina. We find
      KIF3A at two distinct sites within photoreceptors: at the basal body of the
      connecting cilium axoneme and at the synaptic ribbon. Immunoelectron microscopy
      of the photoreceptor ribbon synapse shows KIF3A to be concentrated both at the
      ribbon matrix and on vesicles docked at the ribbon, a result that is consistent
      with the presence of both detergent-extractable and resistant KIF3A fractions at
      these synapses. KIF3A is also present in the inner plexiform layer, again at
      presynaptic ribbons. These findings suggest that within a single cell, the
      photoreceptor, one kinesin polypeptide, KIF3A, can serve two distinct functions,
      one specific for ribbon synapses.

PMID- 9920665
TI  - A novel pineal night-specific ATPase encoded by the Wilson disease gene.
AB  - We have identified a pineal night-specific ATPase (PINA), a novel splice variant
      of the ATP7B gene disrupted in Wilson disease (WD). PINA expression exhibits a
      dramatic diurnal rhythm in both pineal gland and retina with 100-fold greater
      expression at night than at day. PINA is expressed in pinealocytes and a subset
      of photoreceptors in adult rats and is transiently expressed in the retinal
      pigment epithelium and the ciliary body during retinal development. Nocturnal
      pineal expression of PINA is under the control of a suprachiasmatic nucleus clock
      mediated by superior cervical ganglion innervation of the pineal. In vitro, PINA
      expression in pineal cells can be stimulated by agents activating the cAMP signal
      transduction pathway. PINA is able to restore copper transport activity in
      Saccharomyces cerevisiae deficient in the homologous copper-transporting ATPase
      CCC2, suggesting that this protein may function as a copper transporter in rat
      pinealocytes. These studies suggest a potential role of rhythmic copper
      metabolism in pineal and/or retina circadian function.

PMID- 9920667
TI  - Neurotrophins support the development of diverse sensory axon morphologies.
AB  - The initial outgrowth of peripheral axons in developing embryos is thought to
      occur independently of neurotrophins. However, the degree to which peripheral
      neurons can extend axons and elaborate axonal arborizations in the absence of
      these molecules has not been studied directly because of exquisite survival
      requirements for neurotrophins at early developmental stages. We show here that
      embryonic sensory neurons from BAX-deficient mice survived indefinitely in the
      absence of neurotrophins, even in highly dissociated cultures, allowing
      assessment of cell autonomous axon outgrowth. At embryonic day 11 (E11)-E13,
      stages of rapid axon growth toward targets in vivo, Bax-/- sensory neurons
      cultured without neurotrophins were almost invariably unipolar and extended only
      a rudimentary axon. Addition of neurotrophins caused outgrowth of a second axon
      and a marked, dose-dependent elongation of both processes. Surprisingly,
      morphological responses to individual neurotrophins differed substantially.
      Neurotrophin-3 (NT-3) supported striking terminal arborization of subsets of Bax
      /- neurons, whereas NGF produced predominantly axon elongation in a different
      subset. We conclude that axon growth in vitro is neurotrophin dependent from the
      earliest stages of sensory neuron development. Furthermore, neurotrophins support
      the appearance of distinct axonal morphologies that characterize different
      sensory neuron subpopulations.

PMID- 9920668
TI  - Purification and characterization of astrocyte precursor cells in the developing
      rat optic nerve.
AB  - The signaling interactions that control oligodendrocyte generation from their
      precursor cells have been studied intensively. Much less is known about how
      astrocyte generation is normally controlled. Here we report the purification and
      characterization of astrocyte precursor cells (APCs) from the developing rat
      optic nerve. APCs are antigenically distinct from astrocytes. Both cell types are
      Pax2(+) and vimentin+, whereas astrocytes are GFAP+ and S100beta+, and the
      precursor cells are A2B5(+). In contrast to purified astrocytes, purified APCs
      rapidly die in serum-free culture but can be saved by basic fibroblast growth
      factor (bFGF) and glial growth factor 2 (GGF2). Unlike oligodendrocyte precursor
      cells, APCs do not differentiate by default; their differentiation into GFAP+
      cells is induced by ciliary neurotrophic factor (CNTF) or by leukemia inhibitory
      factor (LIF). Finally, the survival, proliferation, and differentiation of APCs
      were promoted by coculture with other embryonic optic nerve cell types but not
      with purified embryonic retinal ganglion cells, indicating that interactions with
      non-neuronal cells are likely to play an important role in controlling astrocyte
      generation in the developing optic nerve.

PMID- 9920669
TI  - Regulation of neurotrophin receptor expression by retinoic acid in mouse
      sympathetic neuroblasts.
AB  - We have studied the effect of retinoic acid on the expression of the neurotrophin
      receptors trkA, trkC, and p75 by neuroblasts and neurons at different axial
      levels along the embryonic mouse paravertebral sympathetic chain. In dissociated
      cultures of sympathetic neuroblasts, retinoic acid inhibited the developmental
      increase in trkA mRNA expression and the developmental decrease in trkC mRNA
      expression that normally occurs in these cells but did not affect p75 mRNA
      expression. At higher concentrations, retinoic acid also increased the
      proliferation of sympathetic neuroblasts. After sympathetic neuroblasts became
      postmitotic, retinoic acid no longer affected receptor expression. Studies with
      retinoic acid receptor agonists and antagonists indicated that the effects of
      retinoic acid on neurotrophin receptor expression were mediated mainly by alpha
      retinoic acid receptors, not beta or gamma receptors. The observation that alpha
      antagonists increased trkA mRNA expression in intact sympathetic ganglion
      explants suggests that endogenous retinoic acid is a physiological regulator of
      trkA receptor expression.

PMID- 9920670
TI  - Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the
      rodent and primate hypothalamus: a novel circuit implicated in metabolic and
      endocrine regulations.
AB  - Hypocretin (orexin) has recently been shown to increase feeding when injected
      into the brain. Using both rat and primate brains, we tested the hypothesis that
      a mechanism of hypocretin action might be related to synaptic regulation of the
      neuropeptide Y (NPY) system. Hypocretin-immunoreactive terminals originating from
      the lateral hypothalamus make direct synaptic contact with neurons of the arcuate
      nucleus that not only express NPY but also contain leptin receptors. In addition,
      hypocretin-containing neurons also express leptin receptor immunoreactivity. This
      suggests a potential mechanism of action for hypocretin in the central regulation
      of metabolic and endocrine processes. The excitatory actions of hypocretin could
      increase NPY release, resulting in enhanced feeding behavior and altered
      endocrine regulation, whereas leptin, released from adipose tissue as an
      indicator of fat stores, would have the opposite effect on the same neurons,
      leading to a decrease in NPY and NPY-mediated hypothalamic functions. On the
      other hand, the innervation of hypocretin cells by NPY boutons raises the
      possibility that NPY may exert an effect on hypothalamic functions, at least in
      part, via mediation or feedback action on these lateral hypothalamic cells. Our
      data indicate that a direct interaction between leptin, hypocretin, and NPY
      exists in the hypothalamus that may contribute to the central regulation of
      metabolic and endocrine processes in both rodents and primates.

PMID- 9920671
TI  - On the mechanism of the gamma --> beta frequency shift in neuronal oscillations
      induced in rat hippocampal slices by tetanic stimulation.
AB  - Tetanic stimulation of the CA1 region of rat hippocampal slices can induce gamma
      frequency population oscillations (30-100 Hz) after a latency of 50-150 msec that
      are synchronized to within 1-2 msec when simultaneous stimuli are delivered to
      two sites 2 mm or more apart. When tetanic stimuli, twice-threshold for eliciting
      gamma oscillations, are used, new phenomena occur. (1) After a period of gamma,
      there is a switch to beta frequencies (10-25 Hz); (2) during the switch,
      pyramidal cell spike afterhyperpolarizations (AHPs) increase and rhythmic EPSPs
      occur in pyramidal cells; and (3) after an episode of single-site, twice
      threshold-induced gamma/beta oscillations, simultaneous two-site threshold
      stimuli induce gamma oscillations that are locally synchronized, but no longer
      are capable of long-range synchrony. We studied the cellular mechanisms of the
      gamma/beta switch with electrophysiological techniques and computer simulations.
      Our model predicts that the observed increases in both pyramidal cell AHPs and in
      pyramidal/pyramidal cell EPSPs are necessary and sufficient for the beta switch
      to occur. Firing patterns generated by the model, both for pyramidal cells and
      for interneurons, resemble experimental records. A one-site twice-threshold
      stimulus might lead to an inability of the two sites to synchronize at gamma
      frequencies, after subsequent two-site stimulation, via this mechanism. If
      depression is induced at synapses coupling pyramidal cells at one site to
      interneurons at the other site, then two-site stimulation cannot produce
      interneuron doublets; hence, as shown previously, the two sites will be unable to
      synchronize. This mechanism works in simulations, and we provide experimental
      evidence that synaptic depression and loss of doublets occur after a sufficiently
      strong local tetanus to one site. We suggest that long-range excitatory
      connections onto interneurons determine whether different pyramidal cell
      "assemblies" can synchronize at gamma frequencies, whereas excitatory connections
      onto pyramidal cells determine whether such assemblies can synchronize at beta
      frequencies.

PMID- 9920672
TI  - Temporally graded retrograde amnesia of contextual fear after hippocampal damage
      in rats: within-subjects examination.
AB  - We have shown previously that electrolytic lesions of the dorsal hippocampus (DH)
      produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear
      conditioning (). As such, the hippocampus seems to play a time-limited role in
      the consolidation of contextual fear conditioning. Here, we examine retrograde
      amnesia of contextual fear produced by DH lesions in a within-subjects design.
      Unlike our previous reports, rats had both a remote and recent memory at the time
      of the lesion. Rats were given 10 tone-shock pairings in one context (remote
      memory) and 10 tone-shock pairings in a distinct context (with a different tone)
      50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to
      controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but
      recent contextual fear memory was severely impaired. They also did not exhibit
      deficits in tone freezing. This highly specific deficit in recent contextual
      memory demonstrated in a within-subjects design favors mnemonic over performance
      accounts of hippocampal involvement in fear. These findings also provide further
      support for a time-limited role of the hippocampus in memory storage.

PMID- 9920673
TI  - Inhibition of light- or glutamate-induced mPer1 expression represses the phase
      shifts into the mouse circadian locomotor and suprachiasmatic firing rhythms.
AB  - mPer1, a mouse gene, is a homolog of the Drosophila clock gene period and has
      been shown to be closely associated with the light-induced resetting of a
      mammalian circadian clock. To investigate whether the rapid induction of mPer1
      after light exposure is necessary for light-induced phase shifting, we injected
      an antisense phosphotioate oligonucleotide (ODN) to mPer1 mRNA into the cerebral
      ventricle. Light-induced phase delay of locomotor activity at CT16 was
      significantly inhibited when the mice were pretreated with mPer1 antisense ODN 1
      hr before light exposure. mPer1 sense ODN or random ODN treatment had little
      effect on phase delay induced by light pulses. In addition, glutamate-induced
      phase delay of suprachiasmatic nucleus (SCN) firing rhythm was attenuated by
      pretreatment with mPer1 antisense ODN, but not by random ODN. The present results
      demonstrate that induction of mPer1 mRNA is required for light- or glutamate
      induced phase shifting, suggesting that the acute induction of mPer1 mRNA in the
      SCN after light exposure is involved in light-induced phase shifting of the overt
      rhythm.

PMID- 9920674
TI  - Computation of object approach by a wide-field, motion-sensitive neuron.
AB  - The lobula giant motion detector (LGMD) in the locust visual system is a wide
      field, motion-sensitive neuron that responds vigorously to objects approaching
      the animal on a collision course. We investigated the computation performed by
      LGMD when it responds to approaching objects by recording the activity of its
      postsynaptic target, the descending contralateral motion detector (DCMD). In each
      animal, peak DCMD activity occurred a fixed delay delta (15 </= delta </= 35
      msec) after the approaching object had reached a specific angular threshold
      thetathres on the retina (15 degrees </= thetathres </= 40 degrees). thetathres
      was independent of the size or velocity of the approaching object. This angular
      threshold computation was quite accurate: the error of LGMD and DCMD in
      estimating thetathres (3.1-11.9 degrees) corresponds to the angular separation
      between two and six ommatidia at each edge of the expanding object on the locust
      retina. It was also resistant to large amplitude changes in background
      luminosity, contrast, and body temperature. Using several experimentally derived
      assumptions, the firing rate of LGMD and DCMD could be shown to depend on the
      product psi(t - delta). e-alphatheta(t-delta), where theta(t) is the angular size
      subtended by the object during approach, psi(t) is the angular edge velocity of
      the object and the constant, and alpha is related to the angular threshold size
      [alpha = 1/tan(thetathres/2)]. Because LGMD appears to receive distinct input
      projections, respectively motion- and size-sensitive, this result suggests that a
      multiplication operation is implemented by LGMD. Thus, LGMD might be an ideal
      model to investigate the biophysical implementation of a multiplication operation
      by single neurons.

PMID- 9920675
TI  - Different contributions of the hippocampus and perirhinal cortex to recognition
      memory.
AB  - Brain regions involved in visual recognition memory, including the hippocampus,
      have been investigated by measuring differential neuronal activation produced by
      novel and familiar pictures. Novel and familiar pictures were presented
      simultaneously, one to each eye, using a paired viewing procedure. Differential
      neuronal activation was determined using immunohistochemistry for the protein
      products of c-fos as an imaging technique. The results establish that the regions
      of the rat brain associated with discriminating the novelty or familiarity of an
      individual item (such as a single object) differ from those responding to a
      spatial array of items (such as a scene). Perirhinal cortex and area TE of the
      temporal lobe are activated significantly more by pictures of novel than of
      familiar individual objects, but the hippocampus is not differentially activated.
      In contrast, pictures of novel arrangements of familiar items produce
      significantly greater activation than familiar arrangements of these items in
      postrhinal cortex and subfield CA1 of the hippocampus but significantly less
      activation in the dentate gyrus and subiculum; perirhinal cortex and area TE are
      not differentially activated. Thus, the hippocampus is importantly involved in
      processing information essential to recognition memory concerning the relative
      familiarity of arrangements of items, as needed for episodic memory of scenes,
      whereas the perirhinal cortex processes such information for individual items.

PMID- 9920676
TI  - Interaural intensity difference processing in auditory midbrain neurons: effects
      of a transient early inhibitory input.
AB  - Interaural intensity differences (IIDs) are important cues that animals use to
      localize high-frequency sounds. Neurons sensitive to IIDs are excited by
      stimulation of one ear and inhibited by stimulation of the other ear, such that
      the response magnitude of the cell depends on the relative strengths of the two
      inputs, which in turn depends on the sound intensities at the ears. In the
      auditory midbrain nucleus, the inferior colliculus (IC), many IID-sensitive
      neurons have response functions that decline steeply from maximum to zero spikes
      as a function of IID. However, there are also many neurons with much more shallow
      response functions that do not decline to zero spikes. We present evidence from
      single-unit recordings in the Free-tailed bat's IC that this partially inhibited
      response pattern is a result of the inhibitory input to these cells being very
      brief ( approximately 2 msec). Of the cells sampled, 54 of 137 (40%) achieved
      partial inhibition when tested with 60 msec tones, and the inhibition to these 54
      cells occurred primarily during the first few milliseconds of the excitatory
      response. Consequently, the initial component of the response was highly
      sensitive to IIDs, whereas the later component was primarily insensitive to IIDs.
      Each of the 54 "partially inhibited" cells was able to reach complete inhibition
      with very short stimuli, such as simulated bat echolocation calls that invoked
      only the initial, IID-sensitive component. Local application of inhibitory
      transmitter antagonists disabled the short inhibitory input, indicating that this
      response pattern is created within the IC.

PMID- 9920677
TI  - CREB activation mediates plasticity in cultured hippocampal neurons.
AB  - Activation of cyclic AMP dependent kinase is believed to mediate slow onset, long
      term potentiation (LTP) in central neurons. Cyclic-AMP activates a cascade of
      molecular events leading to phosphorylation of the nuclear cAMP responsive
      element binding protein (pCREB). Whereas a variety of stimuli lead to activation
      of CREB, the molecular processes downstream of CREB, which may be relevant to
      neuronal plasticity, are yet largely unknown. We have recently found that
      following exposure to estradiol, pCREB mediates the large increase in dendritic
      spine density in cultured rat hippocampal neurons. We now extend these
      observations to include other stimuli, such as bicuculline, that cause the
      formation of new dendritic spines. Such stimuli share with estradiol the same
      mechanism of action in that both require activity-dependent CREB phosphorylation.
      Our observations suggest that CREB phosphorylation is a necessary, but perhaps
      not sufficient, step in the process leading to the generation of new dendritic
      spines and perhaps to functional plasticity as well.

PMID- 9920678
TI  - Integrated regulation of signal coding and plasticity by NMDA receptors at a
      central synapse.
AB  - The role of NMDA and non-NMDA glutamate receptors in long-term potentiation has
      been intensely investigated, yet recent evidence on the dynamics of synaptic
      depolarization suggests that the original view should be extended. NMDA receptor
      mediated currents, apart from their Ca2+ permeability, show a marked voltage
      dependence, consisting of current increase and slowdown during membrane
      depolarization. During high-frequency synaptic transmission, NMDA current
      increase and slowdown are primed by non-NMDA receptor-dependent depolarization
      and proceed regeneratively. Thus, NMDA receptors make a decisive contribution to
      membrane depolarization and spike-firing. From the data obtained at the mossy
      fibergranule cell synapse of the cerebellum, we propose that the electrogenic
      role of NMDA receptors is functional to LTP induction. Moreover, during LTP, both
      NMDA and non-NMDA receptor currents are potentiated, thus establishing a feed
      forward mechanism that ultimately enhances spike firing. Thus, NMDA receptors
      exert an integrated control on signal coding and plasticity. This mechanism may
      have important implications for information processing at the cerebellar mossy
      fibergranule cell relay.

PMID- 9920679
TI  - Differential emotional experience leads to pruning of dendritic spines in the
      forebrain of domestic chicks.
AB  - Auditory filial imprinting induces quantitative changes of synaptic density in
      the forebrain area mediorostral neostriatum/hyperstriatum ventrale of the
      domestic chick. The aim of the present study was to examine the time window and
      the extent and quality of experience that is required for the induction of these
      synaptic changes. We found that a brief (30 min) experience with the imprinting
      situation (tone stimulus + mother surrogate) is sufficient to induce spine
      elimination, which is detectable on postnatal day 7, but not 80 min after the
      presentation of the imprinting stimuli. This synaptic reorganization requires the
      association of the acoustic imprinting tone with an emotional reward (mother
      surrogate); acoustic stimulation alone does not lead to detectable synaptic
      changes. The results of the present study provide further evidence that juvenile
      emotional learning events, such as filial imprinting, lead to a selective
      synaptic reorganization.

PMID- 9920680
TI  - Apolipoprotein E antibodies affect the retention of passive avoidance memory in
      the chick.
AB  - Isoforms of apolipoprotein E (ApoE) have been implicated as risk factors in
      Alzheimer's disease. We have, therefore, examined the possible role of ApoE in
      memory formation, using a one-trial passive avoidance task in day-old chicks.
      Birds were trained on the task and then at various times pre or post-training
      were injected intracerebrally with anti-ApoE. Immunofluorescence staining
      demonstrated the presence of the antibody bound to the neuropil, close to the
      injection site and adjacent to the ventricle, with a residence time in the brain
      of up to 30 min. Chicks that were injected 30 min pre-training or just post
      training with 5 micrograms/hemisphere of the antibody learned the task, but were
      amnesic when tested at 30 min or at subsequent times up to 24 hr post-training.
      When tested at 24 hr, birds injected 5.5 hr post-training showed unimpaired
      retention. Birds injected with 5 micrograms/hemisphere of anti-ApoA-I (which has
      a brain distribution similar to that of anti-ApoE) at 30 min pretraining showed
      no amnesia, indicating the specificity of the effect to the ApoE. Possible
      mechanisms for this effect are discussed.

PMID- 9920681
TI  - The role and mechanisms of action of glucocorticoid involvement in memory
      storage.
AB  - Adrenal steroid hormones modulate learning and memory processes by interacting
      with specific glucocorticoid receptors at different brain areas. In this article,
      certain components of the physiological response to stress elicited by learning
      situations are proposed to form an integral aspect of the neurobiological
      mechanism underlying memory formation. By reviewing the work carried out in
      different learning models in chicks (passive avoidance learning) and rats
      (spatial orientation in the Morris water maze and contextual fear conditioning),
      a role for brain corticosterone action through the glucocorticoid receptor type
      on the mechanisms of memory consolidation is hypothesized. Evidence is also
      presented to relate post-training corticosterone levels to the strength of memory
      storage. Finally, the possible molecular mechanisms that might mediate the
      influences of glucocorticoids in synaptic plasticity subserving long-term memory
      formation are considered, mainly by focusing on studies implicating a steroid
      action through (i) glutamatergic transmission and (ii) cell adhesion molecules.

PMID- 9920682
TI  - Passive avoidance training and recall are associated with increased glutamate
      levels in the intermediate medial hyperstriatum ventrale of the day-old chick.
AB  - In the young chick, the intermediate medial hyperstriatum ventrale is involved in
      learning paradigms, including imprinting and passive avoidance learning.
      Biochemical changes in the intermediate medial hyperstriatum ventrale following
      learning include an up-regulation of amino-acid transmitter levels and receptor
      activity. To follow the changes of extracellular amino acid levels during passive
      avoidance training, we used an in vivo microdialysis technique. Probes were
      implanted in chicks before training the animals, either on a methylanthranylate-
      or water-coated bead. One hour later, recall was tested in both groups by
      presenting a similar bead. An increase of extracellular glutamate levels
      accompanied training and testing in both groups; during training, glutamate
      release was higher in methylanthranylate-trained than in water-trained chicks.
      When compared with the methylanthranylate-trained chicks during testing, the
      water-trained chicks showed enhanced extra-cellular glutamate levels. No other
      amino acid examined showed significant changes. After testing, the chicks were
      anesthetized and release-stimulated with an infusion of 50 mM potassium.
      Extracellular glutamate and taurine levels were significantly increased in both
      methylanthranylate- and water-trained chicks. The presentation of
      methylanthranylate as an olfactory stimulus significantly enhanced glutamate
      levels, especially in methylanthranylate-trained chicks. The results suggest that
      such changes in extracellular glutamate levels in the intermediate medial
      hyperstriatum ventrale accompany pecking at either the water- or the
      methylanthranylate-bead. The taste of the aversant may be responsible for the
      greater increases found in methylanthranylate-trained birds.

PMID- 9920683
TI  - Consolidation of memory after its reactivation: involvement of beta noradrenergic
      receptors in the late phase.
AB  - Evidence is growing that the cAMP pathway through the cAMP responsive element
      binding protein (CREB) transcription factor plays an important role in long-term
      memory formation (LTM). To study the role of beta-noradrenergic receptors,
      positively linked to the cAMP second-messenger system, in the dynamics of LTM
      processes, we used a memory-reactivation paradigm because recent studies in our
      laboratory confirmed that reactivated memory is labile and undergoes an extended
      reconsolidation process. In an eight-arm maze, rats were trained to choose the
      same three baited arms; 24 hr later, memory was reactivated and then the rats
      were injected intracerebroventricularly at 5 min, 30 min, 60 min, or 5 hr later
      with the beta-antagonist timolol or with saline. The results showed that
      injection of timolol induced amnesia only at the 60 min post-reactivation
      interval, whereas all control groups and groups that were timolol-injected at
      other post-reactivation intervals displayed optimal retention. The delayed
      amnesic action of timolol suggests that beta noradrenergic receptors and the cAMP
      cascade are implicated in the late phase of reprocessing of a remembered event.

PMID- 9920685
TI  - Influence of salt intake, ANG II synthesis and SFO lesion on thirst and blood
      pressure during sodium depletion. Subfornical organ.
AB  - Water intake was elevated in sodium-depleted rats during a daytime salt appetite
      test, but other rats drank a similar amount of water when saline was not
      available for drinking during the test. This water intake stimulated by sodium
      depletion was blocked by an inhibition of angiotensin (ANG) II synthesis with a
      high dose of captopril (100 mg/kg, sc). Captopril did not reduce water intake by
      causing hypotensive shock or uremia, because water and saline intakes were
      increased rather than decreased after a low dose of captopril (5 mg/kg) that also
      reduced blood pressure and elevated blood urea nitrogen. The water intake, but
      not salt appetite, induced by sodium depletion was greatly reduced by a lesion of
      the subfornical organ (SFO) in one-bottle tests, and this was not clearly related
      to any effects of the lesion on blood pressure. A physiological role for ANG II
      in water intake induced by sodium depletion has recently been disputed, but the
      simplest explanation for the data remains that elevated levels of circulating ANG
      II bind to receptors in the SFO to generate daytime water drinking during sodium
      depletion.

PMID- 9920684
TI  - Activation of human auditory cortex in retrieval experiments: an fMRI study.
AB  - In a previous functional magnetic resonance (fMRI) study, a subdivision of the
      human auditory cortex into four distinct territories was achieved. One territory
      (T1a) exhibited functional specialization in terms of a foreground-background
      decomposition task involving matching-to-sample monitoring on tone sequences. The
      present study more specifically determined whether memory-guided analysis of tone
      sequences is part of the T1a specialization. During the encoding periods, an
      arbitrary and unfamiliar four-tone-sequence (melody) played by one instrument was
      presented. The melody-instrument-combination was different in each period. During
      subsequent retrieval periods, learned and additional combinations were presented,
      and the tasks were either to detect the target melodies (experiment I) or the
      target instruments (experiment II). T1a showed larger activation during the
      melody retrieval. The results generally suggest that (1) activation of T1a during
      retrieval is determined less by the sound material than by the executed task, and
      (2) more specifically, that memory-guided sequential analysis in T1a is dominant
      over recognition of characteristic complex sounds.

PMID- 9920686
TI  - A behavioral economic analysis of fat appetite in rats.
AB  - A behavioral economic analysis of rats' consumption of various fat and sweet
      solutions was conducted in order to assess whether rats' fat appetite is readily
      modifiable. According to economic demand theory, changes in the price of a
      reinforcer will produce substantial changes in its consumption under conditions
      in which a substitutable reinforcer is available. Results from income-compensated
      price changes revealed that sucrose, mineral oil and saccharin solutions
      substituted for a corn oil solution: increases in the price of the corn oil led
      to large decreases in its consumption and sizable increases in consumption of
      these alternatives. On the other hand, plain water did not substitute for the
      corn oil solution: increasing the price of the corn oil did not result in nearly
      as marked a change in its consumption nor in consumption of the water. Neither
      the strength of preference for the corn oil under baseline conditions nor the
      caloric content of the alternative solution predicted whether the alternative
      reinforcer substituted for the corn oil. Rather, palatability appeared to be a
      dimension along which substitution was based. These results suggest that fat
      appetite is modified when palatable alternatives are available, independent of
      how strongly the fat is preferred.

PMID- 9920687
TI  - Wheel running simultaneously induces CTA and facilitates feeding in non-deprived
      rats. Conditioned taste aversion.
AB  - Previous findings indicate that wheel running can have either an aversive or an
      appetitive effect. That is, wheel running for 30 min induces conditioned taste
      aversion (CTA) in rats trained while hungry and thirsty but facilitates feeding
      in non-deprived rats. In Experiment 1, wheel running was also found to be
      effective in producing CTA in non-deprived rats. Therefore, Experiment 2 tested
      whether wheel running produces the aversive and appetitive effects
      simultaneously. During each of four training trials, two groups of non-deprived
      rats were given a flavored solution to drink for 10 min. Then those in the wheel
      group were put in running wheels for 30 min whereas those in the cage group spent
      30 min in small cages. Finally, all rats were given a 60-min feeding test. After
      the first trial, the wheel group drank less flavored solution than the cage group
      during each of the remaining trials. The wheel group also ate more than the cage
      group on each feeding test. These results indicate that wheel running produces
      CTA and facilitates eating at the same time. A role for the mesolimbic dopamine
      reward system in these effects was considered.

PMID- 9920688
TI  - Effects of meal composition on blood alcohol level, psychomotor performance and
      subjective state after ingestion of alcohol.
AB  - Moderating effects of meal composition on psychomotor performance impairment and
      feelings after alcohol were examined in a between-subjects design. Fifty-one male
      volunteers fasted or received either a high carbohydrate (85% energy) or a high
      protein (94% energy) meal. Alcohol was administered at a dose to achieve a blood
      alcohol level (BAL) of 60 mg/100 ml, as a placebo. Subjects performed a dual task
      of primary tracking and secondary reaction time and a five-choice reaction time
      task. Feelings were also assessed by rating. The high carbohydrate meal reduced
      BAL at peak and 2 h after drinking, but a high protein meal had no significant
      effect. Although performance was impaired by alcohol, neither meal significantly
      reduced impairment and there was no effect of meal type on performance in the
      placebo condition. However, alcohol increased rated intoxication and the high
      carbohydrate meal reduced this effect. Subjects who had consumed high protein
      meals had more negative affect 2 h after alcohol than did subjects who had
      consumed high carbohydrate meals or fasted. It is concluded that there is only a
      weak relationship between BAL and performance impairment and food has only
      limited effects on impairment, although it reduces BAL.

PMID- 9920689
TI  - Relative contributions of intestinal, gastric, oro-sensory influences and
      information to changes in appetite induced by the same liquid meal.
AB  - To investigate the contribution of oral, gastric and intestinal factors in the
      control of appetitc, 425 ml (400 kcal) tomato soup was administered either
      orally, intragastrically (covertly and overtly) or intraduodenally (overtly) to
      nine healthy, fasted, male volunteers. Ratings of fullness, hunger and desire to
      eat were recorded over a period of 2 h and gastric emptying was measured after
      soup fed orally and intragastrically. Infusion of the soup into the small
      intestine at a rate commensurate with normal gastric emptying exerted no
      significant suppression of ratings of hunger and desire to eat and no significant
      production of fullness. Covert, intragastric infusion of the same soup suppressed
      appetite and this suppression was increased when the subjects were informed of
      the nature of the infusion, but there were no differences in gastric emptying
      profiles between covert and overt intragastric infusions of soup. Oral
      administration of the soup produced the greatest suppression of appetite compared
      with other conditions and also generated a slower rate of gastric emptying
      compared with both intragastric soup infusions. Strong correlations were observed
      between appetite ratings and both gastric and intestinal contents following
      intragastric infusions of the soup meal and these were enhanced following oral
      administration of soup. These results indicate how information, orosensory,
      gastric and intestinal factors can interact to elicit optimal expression of
      fullness and suppression of hunger. Specifically, the data not only demonstrate
      how the influence of gastric distension appears to overwhelm any direct influence
      of intestinal chemostimulation on appetite and how information modulates this
      effect, but the data also support an important role in appetite suppression for
      psychophysiological mechanisms stimulated by orosensory mechanisms.

PMID- 9920690
TI  - Cognitive antecedents of consumers' willingness to purchase fish rich in
      polyunsaturated fatty acids (PUFA).
AB  - A sample of UK consumers (N = 311) was interviewed in order to identify the
      attitudinal, cognitive and involvement characteristics of probable early adopters
      of polyunsaturated fatty acid (PUFA) fed fish. Attitude to fish significantly
      influenced PUFA fish, premium price PUFA fish, PUFA salmon, PUFA eel and PUFA
      sturgeon purchase. Involvement in healthy eating influenced PUFA fish, premium
      price PUFA fish and PUFA salmon purchase. Cognitive style did not influence PUFA
      fish and premium price PUFA fish purchase; nor, contrary to earlier research, did
      cognitive style and involvement interact to influence intended PUFA fish
      purchases.

PMID- 9920691
TI  - Young consumers and the hospitality spectrum.

PMID- 9920692
TI  - Food intake equals meal size times mean number.

PMID- 9920693
TI  - Plasticity of quantal size in ventral midbrain dopamine neurons: possible
      implications for the neurochemistry of feeding and reward.

PMID- 9920695
TI  - Prevention of Obesity:Berzelius/ICO Symposium.

PMID- 9920694
TI  - Pharmacology of food conditioned preferences.

PMID- 9920697
TI  - COLUMBIA UNIVERSITY SEMINAR ON APPETITIVE BEHAVIOR.

PMID- 9920698
TI  - Volume Contents and Index to Volume 31.

PMID- 9920699
TI  - Measurements and Calculations of the Halfwidth of Two Rotational Transitions of
      Water Vapor Perturbed by N2, O2, and Air.
AB  - In this paper we report the results of both an experimental and theoretical study
      of the halfwidths of two transitions of water vapor. Measurements on the lines of
      the H216O and H218O isotopomers located at 325.1 and 203.4 GHz, respectively,
      were carried out in the temperature range 300-393 K, with N2 and O2 as perturbing
      gases. The foreign-broadening coefficients and their temperature-dependence
      parameters were determined assuming a Voigt profile and the usual temperature
      dependence for the halfwidth. The retrieved values are compared to values
      calculated using the complex semiclassical formalism of Robert and Bonamy. The
      assumed intermolecular potential is a combination of electrostatic and atom-atom
      components. This last contribution is defined as the sum of pairwise Lennard
      Jones 6-12 interactions between the atoms of H2O and the atoms of the perturbing
      molecules expanded to eighth order. Also calculated are the pressure-induced
      shifts of the spectral lines for temperatures from 200 to 400 K. Calculated and
      experimental results are in good agreement, within +/-3.2%, except for the N2
      broadening temperature coefficients, for which there are discrepancies as high as
      23%. Air-broadening parameters are determined following the classical relation:
      gamma (air) = 0.79gamma (N2) + 0.21gamma (O2). Copyright 1999 Academic Press.

PMID- 9920700
TI  - Application of Deformational Self-Consistent Procedure and New Potential
      Expansion to Effective Reduction of Wavenumbers of Rotational and Vibration
      Rotational Transitions of GeS X1Sigma+
AB  - A deformationally self-consistent procedure and new expansion of the internuclear
      potential energy are applied to reduce the wavenumbers of 727 pure rotational and
      vibration-rotational transitions of nine isotopic variants of GeS to seven radial
      parameters with varsigma; = 1.048, varsigma = 0.00015 cm-1 and F = 1.32 x 10(15).
      A potential energy is expanded into a series of the variable xi = (R - R0)/[aR +
      (1 - a)R0] with a treated as a free-fitted parameter. For GeS, we evaluated a =
      1.09255(81). This new expansion includes those of Dunham, Simons-Parr-Finlan, and
      Ogilvie as special cases corresponding to a = 0, 1, 12. Copyright 1999 Academic
      Press.

PMID- 9920701
TI  - On the Rotational Analysis of the Ground Vibrational State of CH3D Molecule.
AB  - The rotational analysis in the ground vibrational state has been carried out for
      CH3D by using the ground state combination differences. More than 1500 allowed
      and 2500 forbidden transitions from the fundamental bands nu3, nu5, and nu6 were
      used to determine 12 rotational parameters, which reproduce the observed
      combination differences within an accuracy of 1.0 x 10(-4) cm-1. Altogether ten
      independent a1-a2 (K = 3) splittings with J >/= 10 in the vibrational ground
      state were observed and analyzed both with supercombination differences method
      [O. N. Ulenikov, S. Alanko, M. Koivusaari, and R. Anttila, Chem. Phys. Lett. 268,
      242-248 (1997)] and by generating energy levels from Hamiltonian. Problems in
      simultaneous determination of epsilon; and &htilde;3 constants responsible for
      such splittings are discussed. Copyright 1999 Academic Press.

PMID- 9920702
TI  - Laser-Spectroscopic Investigation of Higher Excited Electronic States of the KAr
      Molecule.
AB  - Higher excited electronic states of the van der Waals molecule 39KAr have been
      investigated using a supersonic beam and a two-step excitation. Four hundred
      seventy Doppler-free lines have been observed in the second step leading to the
      electronic states 5d2Sigma, 5d2Pi, 5d2Delta, and 7s2Sigma. The spectroscopic
      parameters of rotation, of spin-orbit splitting, of spin-rotation coupling, and
      of lambda-type doubling have been determined for altogether 19 vibrational levels
      of these electronic states. The molecular spin-orbit splitting turns out to be 
      0.42 cm-1 for 5d2Delta and -0.15 cm-1 for 5d2Pi, which is in fair agreement with
      the theoretical prediction for a Hund's coupling case a. The vibrational
      numbering was deduced from theoretical calculations of the interatomic potential.
      Six vibrational levels have been assigned to the 5d2Delta and the 5d2Sigma state,
      respectively, allowing a determination of the Dunham coefficients in these two
      states. For the equilibrium parameters of the 5d2Delta state, we obtain Re =
      3.22(15) A, De = 900(80) cm-1. Copyright 1999 Academic Press.

PMID- 9920703
TI  - Millimeter-Wave Spectrum of Fluorodiacetylene
      (H&sbond;C&tbond;C&sbond;C&tbond;C&sbond;F).
AB  - The millimeter-wave spectrum of HCCCCF was observed in the ground state as well
      as in the low-lying vibrationally excited states nu7, nu8, nu9 and also
      associated nu8 + nu9, 2nu9, and 3nu9 states. The HCCCCF molecule was produced by
      a dc glow discharge in a flowing vapor of 2,3,4,5,6-pentafluorostyrene. The l
      type doubling constants determined are in good agreement with the values
      predicted from the harmonic force field calculation. Copyright 1999 Academic
      Press.

PMID- 9920704
TI  - Pressure-Induced Frequency Lineshifts in the nu2 Band of Ammonia: An Experimental
      Test of the Rydberg-Ritz Principle.
AB  - Self-induced frequency lineshifts of NH3 in the nu2 band have been measured for
      low J and K values. By combination with lineshift parameters previously published
      for other frequency ranges, it is possible to consider several level manifolds
      connected by superabundant numbers of transitions. Using statistical tests, these
      results lead to a quite meaningful experimental confirmation of the nonadditivity
      of pressure lineshifts, that is, the Rydberg-Ritz combination principle cannot be
      extended to collisionally perturbed systems. Copyright 1999 Academic Press.

PMID- 9920705
TI  - Thermochemical Properties (D degrees0 and IP) of the Lanthanide Monohalides.
AB  - Thermochemical data for the lanthanide monohalides have been combined with recent
      ligand field theory calculations (A. L. Kaledin, M. C. Heaven, R. W. Field, and
      L. A. Kaledin (1996). J. Mol. Spectrosc. 179, 310) to estimate the dissociation
      energies and ionization potentials for all LnX (where Ln in Ba through Lu, and X
      in F, Cl, Br, or I) molecules and the dissociation energies for the LnX+ ions.
      Owing to the negligible involvement of the core-like 4f electrons in bonding, the
      dissociation energies and ionization potentials of all LnX molecules, where Ln in
      Ba through Lu, and X in O, S, F, Cl, Br, or I, should vary with Ln atom in a
      simple linear manner, provided that corrections are made for differences in f
      orbital occupancy between the LnX molecule and the free Ln atom or between the
      LnX molecule and the LnX+ molecular ion. We provide such a model here and, in so
      doing, correct several inconsistencies in the thermochemical data. Based on
      thermochemical data (A. A. Kitaev, I. S. Gotkis, P. G. Val'kov, and K. C. Krasnov
      (1996). Russ. Chem. Phys. 7, 1685) and recent spectroscopic observations (M. C.
      McCarthy, J. C. Bloch, R. W. Field, and L. A. Kaledin (1996) J. Mol. Spectrosc.
      179, 251), a revised value for the ionization potential of DyF, IP(DyF) = 5.85 +/
      0.06 eV, is proposed. Copyright 1999 Academic Press.

PMID- 9920706
TI  - High-Resolution UV Laser Spectroscopy of Jet-Cooled Benzene Molecules: Complete
      Rotational Analysis of the S1 <-- S0 6(1)0 (l = +/-1) Band.
AB  - The UV spectrum of the 6(1)0 S1 <-- S0 vibronic transition of benzene, located at
      259 nm, was recorded by means of a combination of a cw laser doubling unit and a
      molecular beam apparatus. A typical linewidth of 27 MHz was observed, limited
      only by residual Doppler broadening in the supersonic beam. Together with an
      estimated rotational temperature of 25 K, the rotational band structure could be
      completely resolved, and nearly 900 transitions were assigned in the spectrum. A
      set of 13 molecular parameters of the vibronic transition was simultaneously
      adjusted to the measured data by means of a weighted nonlinear least-squares fit
      procedure. The weights themselves were determined by a careful analysis of the
      uncertainties in the measured line frequencies. The overall rms deviation of the
      fit was 3.1 MHz or about 10% of the observed linewidth. Monte Carlo simulations
      were applied to the best-fit parameter set in order to find error estimates for
      the single constants as realistic as possible. The interdependencies of the
      parameters were analyzed by means of correlation coefficients obtained from the
      fit output. These statistical findings were incorporated into comparisons with
      results from other works. As far as ground state-related data are concerned
      general agreement with IR-band investigations was found. In the electronically
      excited state, however, data are scarce and both centrifugal distortion and
      higher order Coriolis coupling parameters were determined for the first time.
      Copyright 1999 Academic Press.

PMID- 9920707
TI  - Experimental Born-Oppenheimer Potential for the X1Sigma+ Ground State of HeH+:
      Comparison with the Ab Initio Potential.
AB  - All literature on vibration-rotational and pure rotational transition energies
      for the X1Sigma+ state of 4HeH+, 3HeH+, 4HeD+, and 3HeD+ have been employed in a
      direct least-squares fit of the radially dependent Hamiltonian. The Born
      Oppenheimer potential is represented by a modified Lennard-Jones function that
      provides for correct behavior in the near dissociation long-range region. Only 19
      adjustable parameters were required to represent the 166 measured transition
      energies, which are reproduced almost to within the measurement accuracies. The
      fitted potential and Born-Oppenheimer breakdown functions are shown to be in good
      agreement with the results of ab initio calculations. The results are used to
      obtain high-order centrifugal distortion constants as well as level widths for
      quasi-bound levels. Copyright 1999 Academic Press.

PMID- 9920708
TI  - Collision-Induced Absorption by CO2 in the Region of nu1, 2nu2.
AB  - Collision-induced absorption (CIA) by CO2 is measured in the 1100-1600 cm-1 range
      using a Fourier-transform spectrometer with a resolution of 0.5 cm-1. The current
      measurements, which agree well with previous ones but are more precise, reveal
      pronounced structures on top of both unresolved Fermi doublet bands consisting of
      P-, Q-, and R-like branches. Assignment of Q-branches at 1284.75 cm-1 and 1387.75
      cm-1 to (CO2)2 dimers seems highly probable. The nature of other peaks observed
      in CIA and Raman spectra of the CO2 Fermi doublet region is discussed. Copyright
      1999 Academic Press.

PMID- 9920709
TI  - A Combined Analysis of Laser Optogalvanic and Fourier Transform Emission Spectra
      of NH2 near its Barrier to Linearity.
AB  - The A2A1-&Xtilde;2B1 electronic transition of NH2 is reinvestigated in the region
      of its barrier to linearity. A detailed rotational analysis is performed on its
      laser optogalvanic spectrum recorded in the region 11 300-14 300 cm-1 and on its
      near infrared Fourier transform emission spectrum. Many new excited levels are
      identified resulting from more than 2900 assigned lines. A number of them are
      high levels of &Xtilde;2B1. A set of molecular parameters has been obtained.
      Numerous perturbations are detected and discussed. This analysis confirms the
      predictions obtained from previous calculations and allows the estimation of
      their accuracy. Copyright 1999 Academic Press.

PMID- 9920710
TI  - The 0 --> 3 Overtone Band of CO: Precise Linestrengths and Broadening Parameters.
AB  - Linestrengths and self-broadening parameters are determined with a standard
      uncertainty of 1% for 21 lines in the R branch of the 0 --> 3 overtone band of CO
      around 1.57 um. The values are lower than those given in the Hitran database by 6
      8% for the linestrengths and 1-5% for the collision broadening parameters, and
      they agree within 0-2% with more recent results obtained with FTIR. Also, results
      are given for foreign gas broadening by N2 and H2O. The line profiles show clear
      evidence for collisional narrowing with deviations corresponding to those
      expected for a Galatry profile. When analyzed in terms of a Voigt profile, this
      effect causes a reduction in effective Doppler width of about 5%. The
      linestrengths determined for gas mixtures are used for producing independent
      values for the CO concentrations. These results are derived without reference to
      any certified gas standard, and it is suggested that optical spectroscopy
      satisfies the criteria of a primary method set up by the Consultative Committee
      for Quantity of Matter (CCQM). Copyright 1999 Academic Press.

PMID- 9920711
TI  - Fourier Transform Emission Spectroscopy of the A' 1Pi-X1Sigma+ and A1Pi-X1Sigma+
      Systems of IrN.
AB  - The emission spectrum of IrN has been investigated in the 10 000-20 000 cm-1
      region at 0.02 cm-1 resolution using a Fourier transform spectrometer. The bands
      were excited in an Ir hollow cathode lamp operated with a mixture of 2 Torr of Ne
      and a trace of N2. Numerous bands have been classified into two transitions
      labeled as A1Pi-X1Sigma+ and A' 1Pi-X1Sigma+ by analogy with the isoelectronic
      PtC molecule. Ten bands involving vibrational levels up to Kv = 4 in the ground
      and excited states have been identified in the A1Pi-X1Sigma+ transition. This
      electronic transition has been previously observed by [A. J. Marr, M. E. Flores,
      and T. C. Steimle, J. Chem. Phys. 104, 8183-8196 (1996)]. To lower wavenumbers,
      five additional bands with R heads near 12 021, 12 816, 13 135, 14 136, and 15
      125 cm-1 have been assigned as the 0-1, 3-3, 0-0, 1-0, and 2-0 bands,
      respectively, of the new A' 1Pi-X1Sigma+ transition. A rotational analysis of
      these bands has been carried out and equilibrium constants for the ground and
      excited states have been extracted. The Kv = 2 and 3 vibrational levels of the A'
      1Pi state interact with the Kv = 0 and 1 levels of the A1Pi state and cause
      global perturbations in the bands. The ground state equilibrium constants for
      193IrN are: omegae = 1126.176360(61) cm-1, omegaexe = 6.289697(32) cm-1, Be =
      0.5001033(20) cm-1, alphae = 0.0032006(20) cm-1, and re = 1.6068276(32) A.
      Copyright 1999 Academic Press.

PMID- 9920712
TI  - Experimental Study of the NaK 3(1)Pi State.
AB  - We report the results of an optical-optical double resonance experiment to
      determine the NaK 3(1)Pi state potential energy curve. In the first step, a
      narrow band cw dye laser (PUMP) is tuned to line center of a particular
      2(A)1Sigma+(v', J') <-- 1(X)1Sigma+(v", J") transition, and its frequency is then
      fixed. A second narrowband tunable cw Ti:Sapphirelaser (PROBE) is then scanned,
      while 3(1)Pi --> 1(X)1Sigma+ violet fluorescence is monitored. The Doppler-free
      signals accurately map the 3(1)Pi(v, J) ro-vibrational energy levels. These
      energy levels are then fit to a Dunham expansion to provide a set of molecular
      constants. The Dunham constants, in turn, are used to construct an RKR potential
      curve. Resolved 3(1)Pi(v, J) --> 1(X)1Sigma+(v", J") fluorescence scans are also
      recorded with both PUMP and PROBE laser frequencies fixed. Comparison between
      observed and calculated Franck-Condon factors is used to determine the absolute
      vibrational numbering of the 3(1)Pi state levels and to determine the variation
      of the 3(1)Pi --> 1(X)1Sigma+ transitiondipole moment with internuclear
      separation. The recent theoretical calculation of the NaK 3(1)Pi state potential
      reported by Magnier and Millie (1996, Phys. Rev. A 54, 204) is in excellent
      agreement with the present experimental RKR curve. Copyright 1999 Academic Press.

PMID- 9920713
TI  - New Rotational Analysis of the B2Sigma+-X2Sigma+ Bands in 69Ga16O and 71Ga16O.
AB  - In the emission spectrum of the Ga16O molecule, the 0-0 and 1-0 bands of the B-X
      system have been rephotographed by means of conventional high-resolution
      spectroscopy. Clear resolution on the rotational structure near the band origins
      made it possible to perform reanalysis of the bands and derive new molecular
      constants characterizing 69Ga16O and 71Ga16O in the B2Sigma+ and X2Sigma+ states.
      Copyright 1999 Academic Press.

PMID- 9920714
TI  - Lowest Overtone and Combination Levels of DCCI: The Fermi Resonance v3 = 1/v5 =
      2.
AB  - The infrared spectrum of deuterated monoiodoacetylene DCCI in the region of 220
      550 cm-1 has been studied at a resolution of 0.0020 cm-1. The hot bands nu3 <--
      nu15 and 2nu0,25 <-- nu15 have been analyzed by considering especially the Fermi
      resonance v3 = 1/v5 = 2. In the next layer of the hot bands (nu3 + nu5)1 <-- nu3,
      (nu3 + nu5)1 <-- 2nu0,25 and 3nu1,35 <-- 2nu25 the same Fermi resonance appears
      between v3 = v5 = 1 and v5 = 3. In addition, various l resonances at the overtone
      levels have been considered. As a result, the vibrational and rotational
      constants for the level systems v3 = 1/v5 = 2 and v3 = v5 = 1/v5 = 3 together
      with the resonance parameters have been obtained. Copyright 1999 Academic Press.

PMID- 9920715
TI  - Double-Resonance Spectroscopic Studies of Core-Penetrating Rydberg States of
      CaCl.
AB  - Six core-penetrating Rydberg series have been assigned in the CaCl molecule by a
      combination of double-resonance spectroscopic techniques. Two 2Sigma+ series,
      with approximate quantum defects (delta) of 0.51 and 0.25, have been observed
      with effective principal quantum numbers (n*) in the range of 5-8 using the
      D2Sigma+ state as the resonant intermediate state for REMPI and/or ion-dip
      detection. A third 2Sigma+ series with delta approximately 0.84 and a 2Delta
      series with delta approximately 0.95 have been observed with n* = 16-18 using the
      A2Pi3/2 state as the resonant intermediate state for preparation of v+ = 1
      vibrationally autoionizing states. Two additional series in the same region with
      delta approximately 0.90 and 0.07 are tentatively identified as the expected core
      penetrating 2Pi series. Vibrational assignments have been confirmed in many cases
      on the basis of isotope shifts between the 35Cl and 37Cl isotopomers. The ion-dip
      and REMPI spectra display linewidths systematically broadened by predissociation.
      In addition to the assigned core-penetrating series, both the REMPI and the ion
      dip spectra display some sharper features that have not yet been assigned. These
      sharper features most likely arise from perturbations of optically "bright" core
      penetrating states by nominally "dark" higher-l core-nonpenetrating states.
      Copyright 1999 Academic Press.

PMID- 9920716
TI  - The Predissociation Mechanism for 2Sigma+ Rydberg States of CaCl.
AB  - This work summarizes experimental results from recent ion-dip spectroscopy
      studies of CaCl and from previously unpublished optical-optical double-resonance
      work with specific regard to predissociation processes of 2Sigma+ Rydberg states
      in the low n* (n* = 7, IP - En* = 2240 cm-1) region. A single repulsive state
      (assigned as 2Sigma+) was found to be responsible for all observed
      predissociations of 2Sigma+ Rydberg states. The n*-dependent internuclear
      distances of the intersections between Rydberg states and the repulsive 2Sigma+
      state were determined through the use of trial-and-error Franck-Condon
      calculations. Values of energy-descaled electronic matrix elements governing the
      Rydberg left and right arrow repulsive state interaction were obtained from the
      measured linewidths (0.6 < Gamma < 1.2 cm-1) and computed Franck-Condon
      densities. Copyright 1999 Academic Press.

PMID- 9920717
TI  - An Analysis of Higher Order Vibration-Torsion-Rotation Interactions and Spectra
      for a Molecule with an Internal Rotor.
AB  - Motivated by attempts to answer the questions (i) if the same order of magnitude
      is really appropriate for the torsional angular momentum terms P2gamma and the
      rotational angular momentum term P2 (or P2a), (ii) how to systematically analyze
      various higher order interaction effects, especially the torsional effects, and
      (iii) if a reduced Hamiltonian can be used to fit observed spectroscopic data to
      an accuracy approaching experimental uncertainties over a significant range of
      quantum states, a detailed discussion is presented on the order of magnitude of a
      Hamiltonian term Hmln for molecules with an internal rotation. A new scheme of
      the ordering by magnitude is proposed to analyze the vibration-torsion-rotation
      (VTR) interactions, in which the importance of the torsional problem is
      emphasized. The contact transformation technique is applied to the VTR
      Hamiltonian, which makes it possible to analyze clearly various higher order VTR
      interactions and their effects in the VTR spectra of the molecule. The resulting
      formulas are applicable to analyze observed spectra. A reduced torsion-rotation
      Hamiltonian for the molecule with C3v(M) symmetry is given in the new ordering
      scheme. As an application, a total of 568 microwave lines with vt </= 3, J </= 42
      and K </= 8 for CH318OH have been fitted to 64 molecular constants by using the
      reduced Hamiltonian with a root mean square (rms) of 0.262 MHz, where the A and E
      substates are treated simultaneously. About 35 newly assigned lines are added to
      our former fitting data (M. Ikeda, Y. B. Duan, S. Tsunekawa, and K. Takagi, ApJS,
      117, 249 (1998)). Copyright 1999 Academic Press.

PMID- 9920718
TI  - Rovibronic Spectroscopy of MgCH3 A2E <-- &Xtilde;2A1 Transition.
AB  - We report the laser excitation and dispersed fluorescence spectra of the A2E <--
      &Xtilde;2A1 transition of the jet-cooled MgCH3 radical. Improvements to the
      experiment have allowed the observation of 6(1)0 and 2(1)0 vibronic features not
      previously observed. Analyses of these bands, along with the previously reported
      0(0)0 spectra, yield the rotational constants and values of the Coriolis and the
      spin-orbit coupling constants for the radical's A2E state. We also are able to
      rather completely characterize a small, dynamic Jahn-Teller effect. The dispersed
      fluorescence spectrum was analyzed and all observed &Xtilde;2A1 state vibrational
      features were assigned. Copyright 1999 Academic Press.

PMID- 9920719
TI  - The b1Sigma+g-X3Sigma-g (3, 0) Band of 16O2 and 18O2.

PMID- 9920722
TI  - Senescence marker protein-30 (SMP30): structure and biological function.
AB  - Senescence marker protein-30 (SMP30), which we previously identified, is notable
      for its androgen-independent decrease in the livers of aging rats. Hepatocytes
      and renal tubular epithelia express large amounts of SMP30 in their cytosol
      throughout the tissue-maturing process and adulthood, but its level decreases
      thereafter. Upon cloning cDNAs that encode SMP30 in rats, mice, and humans, we
      found that the amino acid sequence of SMP30 is well conserved with remarkable
      homology among these species. However, this gene, which is so strongly conserved
      in these higher animals, does not appear in yeast. We also determined the genome
      organization and 5' flanking region of SMP30 in mouse genome. In the meantime,
      SMP30 turned out be identical to a Ca2+-binding protein called regucalcin (RC).
      To learn how this protein functions, we transfected Hep G2 cells with human SMP30
      cDNA so that these cells stably express large amounts of SMP30. The results
      suggest that SMP30 regulates Ca2+ homeostasis by enhancing Ca2+-pumping activity
      in the plasma membranes. Thus, SMP30 seems to play a critical role in the highly
      differentiated functions of the liver and kidney and to exert a major impact on
      Ca2+ homeostasis. If so, down-regulation of SMP30 with aging would attribute
      greatly to the related deterioration of these organs, as indicated in this brief
      overview of the structure, expression, and function of SMP30.

PMID- 9920723
TI  - Stimulation side-dependent asymmetrical secretion of poly I:poly C-induced
      interferon-beta from polarized epithelial cell lines.
AB  - Mode of secretion of poly I:poly C-induced IFN was examined using epithelial cell
      lines in a bicameral culture system. Although the cell lines formed a tight cell
      sheet and produced IFN-beta following poly I:poly C treatment in spite of its
      application to the upper or lower compartment, IFN secretion differed between the
      apical and basolateral cell membranes. When poly I:poly C was applied to the
      upper compartment, IFN was secreted predominantly from the apical membrane.
      Inversely, poly I:poly C applied to the lower compartment caused preferential IFN
      secretion from the basolateral membrane. These results suggest that in epithelial
      cells poly I:poly C stimulation induces intracellular membrane traffic toward the
      stimulation side.

PMID- 9920724
TI  - Differential subcellular localization of the survival motor neuron protein in
      spinal cord and skeletal muscle.
AB  - To compare the expression pattern of the survival motor neuron (SMN) protein in
      spinal cord and skeletal muscle, we generated a sheep polyclonal antibody against
      a bacterially expressed human SMN-fusion protein. On Western blots, the affinity
      purified anti-SMN antibody recognized a approximately 38 kDa protein band in
      extracts prepared from the mouse skeletal muscle, spinal cord, and brain that co
      migrated with the bacterially expressed SMN protein. In immunohistochemical
      studies, the anti-SMN antibody labeled mostly the cytoplasm of the motor neurons
      in the anterior horn of mouse spinal cord. In contrast, predominant uniform
      labeling of the nuclei was observed in the mouse skeletal muscle. Thus, our
      results for the first time demonstrate that the SMN protein is differentially
      localized in mouse spinal cord and skeletal muscle.

PMID- 9920725
TI  - The human vasoactive intestinal Peptide/Pituitary adenylate cyclase activating
      peptide receptor 1 (VPAC1): constitutive activation by mutations at threonine
      343.
AB  - The human vasoactive intestinal peptide/pituitary adenylate cyclase activating
      peptide receptor1 (VPAC1) belongs to the class II subfamily of G protein-coupled
      receptors. Specific changes by mutagenesis of a strictly conserved threonine (H)
      into lysine (K), proline (P) or alanine (A) at position 343 of the human VPAC1
      receptor resulted in its constitutive activation with respect to cAMP production.
      Transfection of these mutants into Cos cells evoked a 3.5 fold-increase in the
      cAMP level as compared to cells transfected with the wild-type receptor. In
      contrast other mutants such as T343C, T343E or T343F were not constitutively
      activated. They were otherwise expressed at the cell surface of transfected
      nonpermeabilized cells. Double mutants were then constructed in which the T343K
      mutation was associated with a point mutation in the the N-terminal extracellular
      domain that totally abolished VIP binding or VIP-stimulated cAMP production i.e.
      E36A or D68A. The corresponding double mutants T343K-E36A and T343K-D68A were no
      longer constitutively activated. A control double mutant (T343K-D132A) with an
      unaltered dissociation constant for VIP and cAMP response to VIP, was still
      constitutively activated. Our findings demonstrate that constitutive activation
      of the VPAC1 receptor can be evoked by specific mutations of T343 at the junction
      of the second intracellular loop and fourth transmembrane segment. This
      constitutive activation appears to require the functional integrity of the N
      terminal extracellular VIP binding domain.

PMID- 9920727
TI  - Role of heterocellular Gap junctional communication in endothelium-dependent
      smooth muscle hyperpolarization: inhibition by a connexin-mimetic peptide.
AB  - A synthetic connexin-mimetic peptide (Gap 27 peptide) was used to evaluate the
      contribution of gap junctional communication to smooth muscle responses mediated
      by the endothelium-dependent agonist acetylcholine (ACh) in rabbit mesenteric
      arteries. Hyperpolarizations and relaxations to 0.1 and 1 microM ACh observed in
      the presence of nitric oxide synthase and cyclooxygenase inhibition were markedly
      attenuated by the peptide at a concentration of 300 microM, whereas the
      hyperpolarizing response to levcromakalim, a KATP channel opener, was unaffected.
      The peptide also attenuated intercellular transfer of Lucifer yellow in confluent
      cultures of COS-7 cells, thus confirming its ability to modulate the permeability
      of gap junctions. The findings demonstrate that heterocellular gap junctional
      communication contributes to NO- and prostanoid-independent mechanisms of
      vasorelaxation that are widely attributed to an endothelium-derived
      hyperpolarizing factor.

PMID- 9920726
TI  - Molecular cloning and characterization of mammalian homologues of vesicle
      associated membrane protein-associated (VAMP-associated) proteins.
AB  - We have identified human and rat homologues of the VAMP-associated protein (VAP)
      of 33 kDa of Aplysia californica (aVAP-33), which we designated VAP-A, VAP-B, and
      VAP-C. Human VAP-A (hVAP-A) was found to be identical to the recently reported
      protein hVAP-33, with the exception of two amino acid residues. VAP-B contained a
      coiled-coil domain and a transmembrane domain (TMD). Human VAP-B (hVAP-B) was 46
      and 60% homologous of the amino acid level to aVAP-33 and hVAP-A, respectively.
      Human VAP-C was a splicing variant of hVAP-B, lacking both the coiled-coil domain
      and the TMD. hVAP-B had VAMP-binding ability. Moreover, hVAP-A and hVAP-B
      associated with each other through their respective TMDs. These results suggest
      that complex formation by VAPs might be important in the trafficking of mammalian
      vesicle.

PMID- 9920728
TI  - Solution structure determination by two-dimensional 1H NMR of omega-conotoxin
      MVIID, a calcium channel blocker peptide.
AB  - The three-dimensional structure of omega-conotoxin MVIID has been determined in
      aqueous solution by two-dimensional 1H NMR techniques. A total of 267 relevant
      upper-bound distance restraints were used to obtain a family of convergent
      structures using molecular dynamics methods. A standard simulated annealing
      protocol using the XPLOR program included in ARIA provided a total of 18 final
      structures. The averaged RMSD between these structures and the mean atomic
      coordinates was 0.8 +/- 0.3 A for the backbone atoms. The highest mobility was
      observed in the segments between residues 10 to 13, comprising Tyr 13, one of the
      residues shown to be important for binding of omega-conotoxin GVIA and MVIIA to N
      type calcium channels. The three-dimensional structure is stabilised by the three
      disulfide bonds and includes a short antiparallel beta-strand between residues 5
      8, 23-25 and 19-21. The folding for this non-N-type calcium channel blocker is
      similar to that previously calculated for omega-conotoxins GVIA, MVIIA and MVIIC.
      This suggests the disulfide bond pattern fixes the structure. The reported three
      dimensional information can be used to advantage in order to highlight the
      structural parameters involved in discrimination among calcium channel subtypes.

PMID- 9920729
TI  - Role of the C-terminal extension in the interaction of S100A1 with GFAP, tubulin,
      the S100A1- and S100B-inhibitory peptide, TRTK-12, and a peptide derived from
      p53, and the S100A1 inhibitory effect on GFAP polymerization.
AB  - Whereas native and recombinant S100A1 inhibited GFAP assembly, a truncated S100A1
      lacking the last six C-terminal residues (Phe88-Ser93) (S100A1Delta88-93) proved
      unable to do so. The inhibitory effects of native and recombinant S100A1 on GFAP
      assembly were blocked by both TRTK-12, a synthetic peptide derived from the alpha
      subunit of the actin capping protein, CapZ, and a synthetic peptide derived from
      the tumor-suppressor protein, p53, in a dose-dependent manner. By fluorescent
      spectroscopy, TRTK-12 and the p53 peptide, like GFAP and tubulin, caused a dose-
      and Ca2+-dependent blue-shift of the fluorescence maximum of acrylodan-S100A1. In
      contrast, GFAP, tubulin, TRTK-12, or the p53 peptide caused no significant
      changes in the fluorescence spectrum of acrylodan-S100A1Delta88-93. By chemical
      crosslinking, both TRTK-12 and the p53 peptide strongly reduced or blocked the
      formation of GFAP-S100A1 or tubulin-S100A1 complexes, respectively, and
      S100A1Delta88-93 was unable to complex with tubulin, whereas a remarkably reduced
      complexation of GFAP with the truncated protein was observed. All the above
      observations show that the C-terminal extension of S100A1 is an essential part of
      the S100A1 site implicated in the recognition of GFAP, tubulin, p53, and the
      alpha-subunit of CapZ.

PMID- 9920730
TI  - cDNA cloning and distribution of the Xenopus follistatin-related protein.
AB  - Recently, several proteins which have a follistatin module have been isolated.
      One of them, the follistatin-related protein (FRP), is encoded by TSC-36 (TGF
      beta-stimulated clone 36) in mouse, originally isolated as a cDNA clone up
      regulated by TGF-beta1 in mouse osteogenic MC3T3E1 cells. To determine the
      physiological role of FRP in early Xenopus embryonic development, we cloned the
      Xenopus FRP (xFRP) cDNA. The resulting cDNA clone was a secreted glycoprotein
      consisting of 299 amino acid residues with about 70% similarity to the mammalian
      and avian FRPs. Northern blotting analysis revealed that xFRP gene expression
      started at stage 10, the onset of gastrulation, gradually increased during the
      blastula and neurula stages and was sustained through the tail-bud stage. Whole
      mount in situ hybridization analysis showed the localization of xFRP mRNAs in the
      Spemann organizer, notochord, neural floor plate, hypochord and somite. The
      similarities with the pattern of expression of Xenopus follistatin mRNA suggests
      that xFRP may play a role in neuralization.

PMID- 9920732
TI  - The T0 domain of rabbit KV1.3 regulates steady state channel protein level.
AB  - The Shaker superfamily encodes voltage-gated potassium (Kv) channels. The amino
      (N) terminus is important for channel assembly and mediates fast inactivation. We
      recently isolated a Kv channel from rabbit kidney, denoted rabKv1.3 (Yao et al.,
      J. Clin. Invest. 97, 2525-2533, 1996) and found that deleting a region (T0
      domain, amino acids 3-39) proximal to the T1 recognition domain (a.a 42-185)
      leads to a 13-fold amplification of Kv current as compared to wild type channels
      (Yao et al., BBRC 249, 492-498). Here we show that deleting the T0 domain affects
      neither single channel conductance nor channel open probability. Instead, it
      increases the absolute number of channel proteins present in the membrane. We
      conclude that the T0 domain is a previously unrecognized Shaker Kv1.3, N-terminal
      regulatory region that modulates steady state channel protein density in the
      plasma membrane.

PMID- 9920731
TI  - Reconstituted 3-dimensional human skin as a novel in vitro model for studies of
      carcinogenesis.
AB  - EpiDerm (MatTek Co., MA) is a reconstituted human skin equivalent which exhibits
      morphological and growth characteristics similar to human skin. This model has
      previously been utilized to evaluate the cytotoxicity and irritant potential of
      various cosmetic and household products. In this study, we show for the first
      time that EpiDerm can be used successfully to evaluate the genotoxicity of
      different types of known carcinogenic agents such as benzo[a]pyrene (BaP),
      ultraviolet B radiation (UVB), ultraviolet A radiation (UVA), and psoralen
      ultraviolet A radiation (PUVA) at the molecular level. The topical application of
      50 microg/cm2 BaP to EpiDerm resulted in the accumulation of BaP-DNA adducts and
      c-fos and p53 proteins as evidenced by immunohistochemical localization.
      Similarly, exposure to UVB (50 mJ/cm2) and UVA (2.5 J/cm2) enhanced the epidermal
      expression of c-fos and p53 proteins in the human skin equivalent. PUVA treatment
      of EpiDerm, however, resulted in the formation of both DNA-8-MOP adducts and
      augmented expression of c-fos and p53 proteins. Most of these changes reached a
      peak 8 h after the treatments except in the case of UVA where maximum changes in
      the expression of c-fos and p53 proteins were observed 24 h after treatment.
      These results are similar to those previously reported in human and murine skin
      following exposure to BaP, UVB, UVA, or PUVA indicating that human skin
      equivalents can be used as a convenient and cost-effective alternative to animal
      testing for assessing the genotoxicity and mechanism of action of
      mutagens/carcinogens in human skin.

PMID- 9920733
TI  - Bacterial expression, purification, and characterization of a novel mouse
      sulfotransferase that catalyzes the sulfation of eicosanoids.
AB  - Analysis of the nucleotide sequence of a recently cloned mouse sulfotransferase
      cDNA (clone 679153) revealed the presence in its 3'-untranslated sequence of an
      AT-rich region which contains four ATTTA motifs and an TTATTTAT-like sequence,
      commonly found among those encoding inflammation-related proteins. The
      recombinant enzyme expressed in Escherichia coli and purified to near
      electrophoretic homogeneity displayed strong sulfotransferase activities toward
      various prostaglandins, thromboxane B2, and leukotriene E4. These results mark
      the first discovery of the sulfation of eicosanoids catalyzed by a distinct
      sulfotransferase.

PMID- 9920734
TI  - Evolutionary, mechanistic, and predictive analyses of the
      hydroxymethyldihydropterin pyrophosphokinase family of proteins.
AB  - A prediction has been prepared ab initio for the secondary structure of the
      hydroxymethyldihydropterin pyrophosphokinase (HPPK) family of proteins starting
      from a set of aligned homologous protein sequences. Attempts to identify a fold
      by threading failed, judging by the inability to find a threading "hit" that had
      a secondary structure that was plausibly congruent to the predicted secondary
      structure for the HPPK family. Therefore, a set of tertiary structure models was
      assembled ab initio, where alternative models were built and used to select
      between alternative secondary structure models. This prediction report
      illustrates the importance of non-computational approaches to structure
      prediction at its present frontier, which is to obtain medium resolution models
      of tertiary structure.

PMID- 9920735
TI  - Enhanced phosphoinositide hydrolysis via overexpression of phospholipase C beta1
      or delta1 inhibits stimulus-induced insulin release in insulinoma MIN6 cells.
AB  - To study the effects of enhanced phosphoinositide hydrolysis on insulin
      secretion, phosphoinositide-specific phospholipase Cbeta1 (PLCbeta1) or PLCdelta1
      was overexpressed in insulinoma MIN6 cells via adenoviral vectors. Inositol
      phosphate production stimulated by NaF (with AlCl3) in PLCbeta1-overexpressing
      cells and that stimulated by KCl or glucose in both PLCbeta1- and PLCdelta1
      overexpressing cells were greater than that in control cells. In addition,
      reduced phosphatidylinositol-4,5-bisphosphate levels were observed in these cells
      stimulated by NaF or KCl. The greater phosphoinositide hydrolysis was accompanied
      by 25-45% inhibition of insulin secretion. These data suggest that excessive
      phosphoinositide hydrolysis inhibits secretagogue-induced insulin release in MIN6
      cells.

PMID- 9920736
TI  - Some properties of mitochondrial adrenodoxin associated with its nonconventional
      electron donor function toward rabbit liver microsomal cytochrome P450 2B4.
AB  - Mitochondrial adrenodoxin (Adx) was found to cross-react with microsomal
      cytochrome P450 2B4 (CYP2B4) as the terminal electron acceptor. When compared
      with NADPH-cytochrome P450 reductase (P450R), the natural redox partner of
      CYP2B4, Adx was less efficient both in transferring the first electron and in
      coupling the system. The ferredoxin yielded an unusual reverse type I spectral
      change with low-spin CYP2B4, which underwent transformation to a typical type I
      optical perturbation upon deletion of the signal anchor sequence (Delta2-27) of
      the hemoprotein. Truncation of CYP2B4 slightly fostered electron transfer from
      Adx, but was deleterious to reduction of the engineered isozyme by P450R.
      Addition of manganese-substituted cytochrome b5, which failed to serve as an
      electron donor to CYP2B4, augmented the amount of hemoprotein existing in form of
      a low-spin complex with Adx and affected the ferredoxin-dependent reduction
      kinetics through causing a proportional rise in both Km and Vmax. Conservative
      replacement of Asp-76 with glutamate in the Adx molecule was associated with a
      drastic drop in reductive efficiency toward CYP2B4, while spectral binding of the
      mutant to the hemoprotein was marginally changed. The results support the concept
      of an evolutionary relationship between the various cytochrome P450 forms as
      regards the conservation of surface regions participating in contacts with
      heterologous donor proteins.

PMID- 9920737
TI  - Extracellular signal-regulated kinase mediates renal regeneration in rats with
      myoglobinuric acute renal injury.
AB  - In vitro data support that extracellular signal-regulated kinase (ERK) and c-Jun
      N-terminal kinase (JNK), members of mitogen-activated protein (MAP) kinases,
      mediate the signal transduction pathways responsible for the cell proliferation.
      However, in vivo role of these MAP kinases is poorly understood. Intramuscular
      injection of 50% glycerol solution induces acute renal failure in rats. This
      injury is known as a model of rhabdomyolysis in human. To investigate the
      molecular mechanism of the signaling pathway in this injury, we examined the role
      of ERK and JNK. After the glycerol injection JNK was rapidly and transiently
      activated at about 4 h, while the activation of ERK was gradually increased and
      the levels were sustained at least to 24 h. Next, we examined the expression of
      cell-cycle related proteins after the glycerol injection using Western blot
      analysis. The levels of proliferating cell nuclear antigen (PCNA) protein as a
      marker for cell proliferation were induced at 2 h and significantly increased to
      24 h after the injection. In addition, cyclins D1, D2, and D3 as markers for G1
      phase also increased with similar time courses. To examine whether activation of
      ERK and/or JNK are involved in the renal regeneration after the glycerol
      injection, we examined the effect of genistein, which is an inhibitor of tyrosine
      kinase, on the activation of ERK and JNK. Administration of genistein to rats
      with this injury decreased the activation of ERK, but not JNK. The induction of
      PCNA and cyclin D1 was also prevented by this treatment. In this condition, renal
      function was further worsened as compared to control rats. These results provide
      the first evidence that ERK may be involved in the repair process of renal
      tubules damaged by this injury.

PMID- 9920738
TI  - NF-kappaB is involved in the induction of the rat hepatic alpha1-acid
      glycoprotein gene by phenobarbital.
AB  - Phenobarbital, a classical inducer of the drug-metabolizing cytochrome P450
      genes, induces alpha1-acid glycoprotein gene expression through a PB-responsive
      element (PBRE) located at position -142 to -126 from the transcriptional start
      site. The aim of this study was to investigate nuclear protein binding to the
      PBRE sequence after PB treatment. Cycloheximide treatment showed that de novo
      protein synthesis was not required for PB to induce AGP gene expression, pointing
      to post-translational modifications. Studies of the DNA-protein complex with the
      PBRE showed that phosphorylation status is a key regulator of the binding
      capacity of transactivating proteins involved in PB transcriptional activation.
      This DNA-protein complex, analyzed by southwestern blotting and UV cross-linking,
      involves three nuclear factors with molecular weights of 43, 52, and 65 kDa.
      Supershift and competition experiments showed that the 43-kDa factor can be
      related to C/EBPalpha and the 52- and 65-kDa factors to the two subunits of NF
      kappaB.

PMID- 9920739
TI  - L-arginine reduces right heart hypertrophy in hypoxia-induced pulmonary
      hypertension.
AB  - Endothelin (Et) and nitric oxide (NO) may serve as chemical mediators of hypoxia
      induced pulmonary hypertension. Plasma levels of Et1 were elevated 2-fold while
      levels of nitrate, a NO metabolite, decreased in rats exposed to 10 days of
      hypoxia (10% O2). Administration of l-arginine, the precursor for NO, decreased
      Et, increased nitrate, and decreased right ventricular hypertrophy in hypoxic
      animals. By increasing plasma NO levels, the right ventricular hypertrophy and
      right heart failure seen in hypoxia-induced pulmonary hypertension in human
      patients may be prevented.

PMID- 9920740
TI  - Disulfide isomers of alpha-neurotoxins from King cobra (Ophiophagus hannah)
      venom.
AB  - Two novel alpha-neurotoxins, Oh-6A and Oh-6B, isolated from the king cobra
      (Ophiophagus hannah) venom, consist of 70 amino acid residues with 10 cysteine
      residues and share the same amino acid sequences as determined by Edman
      degradation on the peptide fragments generated from the proteolytic hydrolysates.
      Their sequences share 46-53% homology with Oh-4, Oh-5, Toxin a, and Toxin b from
      the same venom. The finding that Oh-6A and Oh-6B had different retention times in
      the reversed-phase column suggested that the two toxin molecules should not have
      the same conformation. Selective reduction on the disulfide bond, Cys26--Cys30,
      at the tip of their loop II structures resulted in the production of the
      partially reduced derivatives eluted at the same position. Under redox
      conditions, the partially reduced Oh-6A and 6B exclusively converted into native
      Oh-6A as evidenced by HPLC analyses. This suggests that Oh-6A and Oh-6B are
      disulfide isomers which probably arise from cis-trans isomerization of the Cys26-
      Cys30 disulfide bond. Alternatively, the two toxins exhibited binding activity
      toward nAChR and lethal toxicity equally. It reflects that the diversity around
      the extra loop at the loop II structure does not exert a significant effect on
      the manifestation of the neurotoxicity of Oh-6A and Oh-6B.

PMID- 9920741
TI  - Extended X-ray absorption fine structure evidence for a single metal binding
      domain in Xenopus laevis nucleotide excision repair protein XPA.
AB  - Nucleotide excision repair (NER) is an important cellular mechanism, conserved
      from bacteria to humans, responsible for eliminating multiple types of
      structurally distinct DNA lesions from the genome. The protein XPA appears to
      play a central role in NER, recognizing and/or verifying damaged DNA and
      recruiting other proteins, including RPA, ERCC1, and TFIIH, to repair the damage.
      Sequence analysis and genetic evidence suggest that zinc, which is essential for
      DNA binding, is associated with a C4-type motif, C-X2-C-X17-C-X2-C. Sequence
      analysis suggests that a second, H2C2-type zinc-binding motif may be present near
      the C-terminal. Seventy percent of the amino acid sequence of Xenopus laevis XPA
      (xXPA) is identical to human XPA and both putative zinc-binding motifs are
      conserved in all known XPA proteins. Electrospray ionization-mass spectroscopy
      data show that xXPA contains only one zinc atom per molecule. EXAFS spectra
      collected on full-length xXPA in frozen (77 K) 15% glycerol aqueous solution
      unequivocally show that the zinc atom is coordinated to four sulfur atoms with an
      average Zn--S bond length of 2.33 +/- 0.02 A. Together, the EXAFS and mass
      spectroscopy data indicate that xXPA contains just one C4-type zinc-binding
      motif.

PMID- 9920742
TI  - 5-Methylcytosine in CpG sites and the reactivity of nearest neighboring guanines
      toward the carcinogen aflatoxin B1-8,9-epoxide.
AB  - The reactivity of guanines in an oligonucleotide containing mutational hot spots
      within the p53 gene (codons 248 and 249), 5'-CCG1G2AG3G4CCCA-3', toward dimethyl
      sulfate (DMS) and aflatoxin B1-8,9-epoxide (AFB1-8,9-epoxide) was investigated by
      a modified Maxam-Gilbert technique. 5-Methylcytosine in the CpG site of codon 248
      did not appear to modulate the reactivity of target guanines G1, G2, G3, and G4
      toward either genotoxin when compared to the sequence containing a nonmethylated
      CpG site. A similar experiment was conducted in which a 0.5-kb fragment of the
      human HPRT gene containing exon 1 and several CpG sites was treated with UV
      activated aflatoxin B1. Results showed that guanine adduct formation was
      independent of the methylation status of the CpG site. These findings are
      discussed in relation to other studies that have shown that cytosine methylation
      has an inhibiting effect, an enhancing effect, or no effect on adduct formation
      with nearby guanine nucleotides.

PMID- 9920743
TI  - An acute oral gavage study of 3beta-acetoxyandrost- 5-ene-7,17-dione (7-oxo-DHEA
      acetate) in rats.
AB  - The present study was done to assess the tolerance of rats for 3-acetoxyandrost-5
      ene-7,17-dione (7-oxo-DHEA-acetate, 7-ODA) when administered as a single oral
      gavage dose. Five groups of Sprague-Dawley rats (Crl:CD (SD) BR VAF/Plus)
      (five/sex/group) were treated with 7-ODA at a dose level of 0 (control), 250,
      500, 1000, or 2,000 mg/kg of body weight in a dose volume of 10 ml/kg. Food and
      water were provided ad libitum. All animals survived in good health to the
      scheduled sacrifice on Day 15. The single oral administration of 7-ODA had no
      apparent effects on body weight. Food consumption was significantly higher for
      all female treated groups during week two; however, the statistically significant
      differences were not considered to be of clinical consequence. Treatment caused
      no apparent changes of gross or microscopic anatomical structures of nine
      different organs. This study demonstrated that the no-observable adverse effect
      level for a single oral dose of 7-ODA in male and female rats was 2,000 mg/kg.

PMID- 9920745
TI  - Spatial and temporal expression of the cystathionine beta-synthase gene during
      early human development.
AB  - We report the cystathionine-beta synthase (CBS) gene expression pattern during
      early human embryogenesis (3 to 6 weeks post conception) by in situ hybridization
      and in fetal and adult tissue by Northern Blot analysis. Probes were chosen to
      recognize either the common sequence to all known CBS mRNAs or the sequences of
      two different major exons 1 issued of we have previously identified. We
      demonstrate by in situ hybridization that CBS is continuously expressed from the
      earliest stages studied (22 days post conception) during embryogenesis in the
      tissues of developing embryos which will after birth present clinical
      abnormalities in homocystinuria patients. It is expressed at an especially high
      level in the neural and cardiac systems until the liver primordium appears. In
      embryonic central nervous system, the whole neural tube and primary brain
      vesicles are labeled. Secondary brain vesicles labeling are dependent on the
      neuroepithelium differentiation. The ventricular layer of the rhombencephalon,
      cranial nerve nuclei and then after cerebellar cortex derived from
      rhombencephalon ventricular layer are strongly labeled. Thalamus and other
      derivatives of the diencephalon plate, the neuroblastic layer of the retina, lens
      and dorsal root ganglia are labeled. After 35 days post conception, CBS mRNAs was
      detected in endocardial cells and in cells derived from the neural crest of the
      heart and in particular developing mesodermic regions such as the primitive
      hepatocytes of the liver, mesonephros vesicles, various endocrine glands and
      developing bones. We could not detect tissue specificity of different probes at
      this embryonic stage. Northern blot analysis consistently detected mRNA species
      in fetal 25 weeks post conception brain, liver and kidney. The common cDNA probe
      revealed the 2.5 and 3.7 kb mRNA species from brain, liver and kidney. The exon
      1b probe detected only the 2.5 kb mRNA and the exon 1c probe the 3.7 kb mRNA in
      these three tissues. In adult tissue, the 1b probe detected only the 2.5 kb mRNA
      and the 1c probe only the 3.7 kb mRNA in the liver.

PMID- 9920744
TI  - An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7, 17-dione (7
      oxo-DHEA-acetate) in rhesus monkeys.
AB  - To test the effects of 7-oxo-dehydroepiandrosterone-3 acetate (hereafter 7-ODA)
      in Rhesus macaques the steroid was administered by oral gavage to two male and
      two female monkeys. Dose levels of 250, 500, and 1,000 mg/kg body weight (BW)/day
      were administered on days 1, 3, and 5 respectively, and 1,000 mg/kg on days 7
      through 11. Each group received the dose in a volume of 10 ml/kg BW. All animals
      survived to the scheduled sacrifice on day 12. No adverse clinical effects of 7
      ODA were observed at the 250 or 500 mg/kg doses. Females vomited on non-treatment
      days and all animals vomited on some days after being given the 1000 mg/kg dose.
      Excessive salivation was observed before or immediately after dosing on days 9
      through 11. Appearance, behavior and body weights were not altered by the
      treatments. Visual examination of all body cavities, and macroscopic and
      microscopic examination of 42 different organs and tissues found no lesions or
      abnormalities.

PMID- 9920746
TI  - Isolation of a low-molecular-weight growth inhibitory factor from hybridoma cell
      cultures.
AB  - A low-molecular-weight growth inhibitory factor was produced by hybridoma cells.
      The number of viable cells in hybridoma cell cultures reached a maximum of about
      5 x 10(5) cells/ml when the inhibitory factor had accumulated to a critical
      level, after which the number of viable cells declined with a concomitant
      increase in the number of dead cells. The growth inhibitory factor was purified
      to apparent homogeneity by ultrafiltration, reverse-phase chromatography, passage
      through cation exchangers, and gel filtration. Analysis by reverse-phase
      chromatography and micellar electrokinetic chromatography using a capillary
      electrophoresis system indicated that the final inhibitory fraction was pure. The
      factor had a molecular weight of 500 or less, as judged by ultrafiltration, and
      its behavior upon ion-exchange chromatography indicated that it was uncharged.
      Its absorbance maximum at 263 nm indicated that it was not a peptide, but that it
      may have a conjugated system of carbon-carbon double bonds.

PMID- 9920747
TI  - Serum amyloid A induces chemotaxis of human mast cells by activating a pertussis
      toxin-sensitive signal transduction pathway.
AB  - Serum amyloid A (SAA) is an acute-phase protein and its concentration increases
      in the blood up to 1000 times during an inflammatory response. Mast cells are
      known to accumulate in various inflammatory processes, some of which are
      associated with increased levels of acute-phase reactants such as SAA. We report
      here that SAA can act as a mast cell chemoattractant. Recombinant SAA at
      concentrations corresponding to those found during the acute phase induced
      directional migration of human mast cells. No chemokinetic effect was observed.
      Preincubation of the cells with pertussis toxin inhibited SAA chemotaxis,
      suggesting that the effect is mediated by G proteins of the Gi class.
      Furthermore, chemotaxis was diminished after pretreatment with genistein, a
      tyrosine kinase inhibitor, or bisindolylmaleimide I, a protein kinase C
      inhibitor. We suggest that SAA may participate in the migration of mast cells to
      inflamed tissues during an acute-phase response, acting through a pertussis toxin
      sensitive signaling pathway.

PMID- 9920748
TI  - Use of benzyl mercaptan for direct preparation of long polypeptide benzylthio
      esters as substrates of subtiligase.
AB  - Subtiligase, a double mutant of subtilisin, has been shown to be capable of
      joining together two unprotected peptide fragments, namely an activated peptide
      ester and a second peptide with a free N-terminal amino group. Inside cells,
      inteins are know to join peptide chains (exteins) by self-extrusion. The SC VMA1
      intein was modified to undergo only in vitro N-terminal cleavage in the presence
      of small nucleophilic compounds, releasing the N-terminal extein. With a proper
      choice of the nucleophilic compounds it is shown that it is possible to generate
      long polypeptides, by molecular biology expression, with such an attached
      reactive ester which is an excellent substrate of the enzyme, subtiligase. This
      approach can successfully extend the current limit of the subtiligase-catalyzed
      fragment condensation method as well as provide another application of the
      recently discovered intein chemistry.

PMID- 9920749
TI  - Mitochondrial DNA deletions in human cardiac tissue show a gross mosaic
      distribution.
AB  - The variability of mitochondrial DNA (mtDNA) deletional patterns has been
      investigated in adjacent slices of human heart atrium. Using quantitative PCR we
      found differential abundances of one particular mtDNA deletion, that of 4977 bp
      (mtDNA4977), among sets of adjacent slices of right atrial trabeculae pectinatae
      from 10 subjects. Some subjects had relatively constant abundance of mtDNA4977
      among the tissue slices, while others covered a wide range. A qualitative PCR
      procedure was used to visualize the patterns of multiple deletions within an 8.64
      kb segment of the mtDNA genome, in the same set of atrial trabeculae samples.
      Some subjects showed completely different multiple deletional patterns in each of
      the trabeculae slices analyzed. There was no correlation between the variation of
      the abundance of mtDNA4977 and that of the multiple deletions. The results are
      consistent with the notion that the occurrence of mtDNA deletions during aging is
      a random process, involving their production throughout the lifetime of an
      individual. In this view, the patterns of new deletions are superimposed on those
      already accumulated by propagation and segregation of mutations formed earlier in
      life.

PMID- 9920750
TI  - The exogenously added small subunit of smooth muscle myosin phosphatase increases
      the Ca2+ sensitivity of the contractile apparatus in the permeabilized porcine
      renal artery.
AB  - The effects of the small noncatalytic subunit of myosin light chain phosphatase
      (MLCPsr) on the Ca2+-induced contraction of smooth muscle were investigated in
      the Triton X-100-permeabilized porcine renal artery. The full-length recombinant
      chicken MLCPsr obtained by the bacterial expression system induced an additional
      contraction at a constant [Ca2+]i and shifted the [Ca2+]i-force relation curve to
      the left. A deletion mutant containing the N-terminal 78 amino acids of MLCPsr
      retained the full action, compared with the full-length MLCPsr, while the
      deletion of this region completely abolished its effect. The process of
      relaxation was also delayed by the fragment containing the N-terminal 78 amino
      acids. These results indicated that MLCPsr increases the Ca2+ sensitivity of the
      contractile apparatus while the N-terminal 78 amino acids are responsible for
      this effect in vascular smooth muscle.

PMID- 9920751
TI  - Rat Hsp20 confers thermoresistance in a clonal survival assay, but fails to
      protect coexpressed luciferase in Chinese hamster ovary cells.
AB  - Hsp20 is a mammalian small heat shock protein with some deviating in vitro
      characteristics. We now compare the in vivo cellular thermoprotective abilities
      of Hsp20 with those of its direct relative, alphaB-crystallin. In a clonal
      survival assay Chinese hamster ovary (CHO) cells stably overexpressing Hsp20
      survive equally well as alphaB-crystallin-expressing cells, after a heat shock.
      In a transient assay, however, overexpression of Hsp20 did not result in an
      enhanced recovery of coexpressed firefly luciferase after heat shock, in contrast
      to alphaB-crystallin. This might indicate that these highly homologous stress
      proteins are involved in at least partially distinct protective activities in
      cultured cells.

PMID- 9920752
TI  - Cyclosporin A induces a biphasic increase in KCl-induced calcium influx in GH3
      pituitary cells.
AB  - The role of calcineurin in modulation of calcium channel activity was examined in
      GH3 pituitary cells by using its selective inhibitor cyclosporin A. While
      cyclosporin A had little effect on basal activity, it induced a biphasic increase
      in K+-induced 45Ca2+ influx. Cyclosporin A rapidly increased K+-induced 45Ca2+
      influx to approximately 140% of control in 1 h and the increment maintained at
      this magnitude for 1-8 h. Thereafter, K+-induced 45Ca2+ influx gradually
      increased further to approximately 220% after 24 h exposure to this compound. In
      the presence of anisomycin, however, the increase occurred at the latter phase
      was abolished. In addition, the increased calcium influx in cyclosporin A
      pretreated cells had a similar sensitivity to KCl and verapamil as in untreated
      cells. Measurement of intracellular Ca2+ level by Fura-2 analysis indicated that
      [Ca2+]i increase induced by high K+ or vasoactive intestinal peptide was
      similarly augmented in cyclosporin A-pretreated cells. Thus the results of this
      study suggest that calcineurin may play a tonic control on L-type Ca2+ channel,
      and inhibition of this enzyme may induce a subsequently protein synthesis
      dependent higher channel activity.

PMID- 9920753
TI  - Secondary structure of sea anemone cytolysins in soluble and membrane bound form
      by infrared spectroscopy.
AB  - Attenuated total reflection (ATR) Fourier transform infrared spectroscopy (FTIR)
      was used to investigate the secondary structure of two pore-forming cytolysins
      from the sea anemone Stichodactyla helianthus and their interaction with lipid
      membranes. Frequency component analysis of the amide I' band indicated that these
      peptides are composed predominantly of beta structure, comprising 44-50% beta
      sheet, 18-20% beta-turn, 12-15% alpha-helix, and 19-22% random coil. Upon
      interaction with lipid membranes a slight increase in the alpha-helical and beta
      sheet structures was observed with a concomitant decrease of the unordered
      structure. Polarisation experiments indicated that both toxins had some
      disordering effect on the lipid layers. The dichroic ratio of the alpha-helical
      component of the membrane-bound toxin was 3.0-3.3, indicating that this element
      was oriented with an angle of 38 degrees-42 degrees with respect to the normal to
      the plane of the crystal surface, thus resulting almost parallel to the mean
      direction of the lipid chains.

PMID- 9920754
TI  - Localisation of cis regulatory elements at the beta-globin locus: analysis of
      hybrid haplotype chromosomes.
AB  - Several cis elements at the beta-globin gene cluster and the upstream locus
      control region (LCR) have been implicated in modulation of fetal haemoglobin (Hb
      F) level in beta-globin disorders. To determine the role of elements at the LCR
      and the beta-globin gene cluster on HbF level among sickle cell anaemia (SCA)
      patients, hybrid haplotype betaS chromosomes exhibiting variation in the
      association of alleles of LCR hypersensitive site 2 (HS2) and the beta-globin
      gene cluster restriction fragment length polymorphosim (RFLP) haplotypes were
      identified in an unselected population of 100 patients. On 15 chromosomes the
      polymorphic HS2 short tandem repeat(TA)xN10-12(TA)y containing a Hox2 binding
      motif differed from that typically associated with the corresponding beta-globin
      gene cluster RFLP haplotype. Among patients homozygous for the Benin RFLP
      haplotype, in whom one chromosome carried the (TA)9N10(TA)10 allele, no effect on
      HbF level was observed. Polymorphism of the pre-Ggamma framework, an enhancer
      located 25 kb downstream of HS2 localised the breakpoint for each of these
      'hybrid' haplotype chromosomes upstream of this element. Previously described
      hybrid haplotype chromosomes with the (TA)9N10(TA)10 HS2 allele associated with
      raised HbF by contrast arise by recombination 1 kb downstream of the pre-Ggamma
      framework. This study suggests that variability in HbF level associated with
      polymorphisn of the HS2 enhancer depend on downstream determinant (s) in tight
      linkage disequilibrium with HS2. The pre-Ggamma framework is the only known
      polymorphic cis-active determinant in this region.

PMID- 9920755
TI  - Soluble guanylate cyclase: effect of YC-1 on ligation kinetics with carbon
      monoxide.
AB  - Recently it has been reported that in the presence of YC-1, a benzyl indazole
      derivative, carbon monoxide activates soluble guanylate cyclase, GC, to about the
      same extent as its best known activator, nitric oxide. Kinetic studies utilizing
      flash photolysis of GC complexed with CO in the presence and absence of YC-1
      show, in contrast to another recent report of a mixing experiment, that YC-1 has
      a profound effect on bimolecular association kinetics and a smaller, but
      significant, effect on ligand affinity. Most prominent is the appearance of a
      major, new phase in the bimolecular recombination kinetics in the presence of 200
      microM YC-1: This major fraction rebinds CO approximately 1000-fold more rapidly
      than in the absence of YC-1. Another portion, considerably less than half,
      exhibits kinetics that are almost exactly the same as in the absence of YC-1. It
      is now clear that both YC-1 and CO have a strong synergistic effect on enzyme
      activity and also a dramatic effect on ligand binding behavior. It is, therefore,
      a reasonable inference that ligand binding at the heme iron atom is intimately
      connected with enzyme activation, a hypothesis that would have been difficult to
      maintain if the earlier report, that YC-1 has no effect on CO binding, were
      correct. Possible reasons for the discrepancy between the two measurements are
      suggested.

PMID- 9920756
TI  - Wilms' tumor gene product WT1 arrests macrophage differentiation of HL-60 cells
      through its zinc-finger domain.
AB  - Wilms' tumor is associated with mutations of WT1, a zinc-finger transcription
      factor that is essential for the development of the metanephric kidney and the
      urogenital system. High levels of WT1 expression also have been detected in
      myeloid leukemia cells, suggesting that WT1 may be important in other neoplasms
      as well. To seek a role of high level expression of WT1 in the differential
      arrest characteristic of myeloid leukemia, WT1 or its zinc-finger domain alone
      was stably expressed in human promyeloid leukemia (HL-60) cells and the ability
      of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to induce macrophage
      differentiation was examined. HL-60 cell differentiation was completely arrested
      in TPA treated cells that expressed WT1 or its zinc-finger domain alone whereas
      TPA fully induced macrophage differentiation in control HL-60 cells, indicating
      that high level expression of WT1 is capable of differentiation arrest of myeloid
      cells and that its effect may be mediated through its zinc-finger domain. To
      determine if the zinc-finger domain of WT1 directly influences transcription, it
      was brought to promoter DNA as a fusion protein with the Gal4 DNA binding domain.
      The fusion protein failed to regulate transcription of a reporter gene but when
      the zinc-finger domain of WT1 was brought to DNA with a promoter containing two
      upstream WT1-binding sites, reporter gene expression was activated approximately
      threefold, suggesting that WT1 interferes with myeloid differentiation through
      the ability of its zinc-finger domain to compete with other transcription factors
      for common promoter elements.

PMID- 9920757
TI  - Imbalanced expression of functionally different WT1 isoforms may contribute to
      sporadic unilateral Wilms' tumor.
AB  - Functional loss of the product of the Wilm's tumor suppressor gene (wt1) has been
      identified in subsets of familial Wilms' tumors. Previously, four alternative
      splice products of WT1 were recognized and each was found to regulate
      transcription of effector genes differently, suggesting that disruption of the
      normal ratio of these spliced products will disrupt the normal expression
      patterns of WT1 effector genes and perhaps lead to Wilms' tumor. In support of
      these suggestions, we found that four of seven cases of sporadic unilateral
      Wilms' tumor had striking differences in the ratios of the spliced products of
      WT1 compared with each other and normal kidney. These data indicate that in
      addition to structural mutations, alterations in the relative amounts of the
      mature WT1 isoforms may also be important in the etiology of sporadic Wilms'
      tumor.

PMID- 9920758
TI  - Nitric oxide inhibits HIV-1 replication in human astrocytoma cells.
AB  - Astroglial cells represent a target for HIV infection in the central nervous
      system. In astrocytes, HIV infection is poorly productive, being characterized by
      a persistent state of viral latency. However, activation of the nuclear factor NF
      kappaB and its binding to HIV long terminal repeat (LTR) can induce HIV
      replication. Moreover, nitric oxide (NO) can affect NF-kappaB activation in glial
      cells. Therefore, we hypothesize that NO may reduce HIV replication in human
      astroglial cells by inhibiting HIV-1 LTR transcriptional activity. In this
      respect, we show that NO donors reduce viral replication in HIV-1-infected human
      astrocytoma T67 cells, taken as an astroglial model. Furthermore, using
      transfected T67 cells, we demonstrate that NO donors inhibit HIV-1 LTR
      transcriptional activity. These results suggest that the use of NO-releasing
      drugs may represent a potential, novel approach in inhibiting HIV replication in
      the central nervous system.

PMID- 9920759
TI  - TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1,
      could enhance apoptosis of some tumor cells induced by growth factor withdrawal.
AB  - Using the cDNA-representative differences analysis (cDNA-RDA) approach, we
      identified a novel gene, TFAR19 (TF-1 cell apoptosis related gene-19), from TF-1
      cells undergoing apoptosis. The human TFAR19 encodes a protein which shares
      significant homology to the corresponding proteins of species ranging from yeast
      to mice. TFAR19 exhibits a ubiquitous expression pattern and its expression is
      upregulated in the tumor cells undergoing apoptosis. Overexpression of TFAR19 in
      tumor cells enhances apoptosis triggered by growth factor or serum deprivation.
      We propose that TFAR19 may play a general role in the apoptotic process.

PMID- 9920760
TI  - Protein kinase C activation increases binding of transcription factor PU.1 in
      murine tissue macrophages.
AB  - PU.1 is a transcription factor found in macrophages, B cells, neutrophils, and
      hemopoietic stem cells. In macrophages PU.1 regulates a number of genes,
      including c-fms, CD11b, CD18, and FcgammaR1b. Previously, in primary macrophages
      PU.1 binding to the sequence GAGGAA was found to be induced by treatment with
      bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Here we
      investigated the role of protein kinase C (pKC) in the induction of PU.1 binding
      in macrophages. We report that pharmacological activation of pKC increases PU.1
      binding, while inactivation of pKC inhibits the increases in PU.1 binding by
      agents which activate pKC in macrophages (LPS and tumor necrosis factor-alpha),
      but not by an agent which does not activate pKC (IFN-gamma). pKC activation may
      therefore be one pathway by which PU.1 binding may be increased in primary
      macrophages.

PMID- 9920761
TI  - Microenvironment of the high affinity ATP-binding site of Na+/K+-ATPase is
      slightly acidic.
AB  - Fluorescein-5'-isothiocyanate (FITC) was used to study the high-affinity ATP
      binding site of Na+/K+-ATPase. The molar ratio of specifically bound FITC per
      alpha-subunit of Na+/K+-ATPase was found to be 0.5 as followed from pretreatment
      experiments with another specific E1ATP-inhibitor Cr(H2O)4AdoPP[CH2]P. This
      indicated an existence of one high affinity ATP-binding site (E1ATP-binding site)
      in the native (alphabeta)2-diprotomer of Na+/K+-ATPase. Fluorescence dual
      excitation ratio of specifically bound FITC revealed that at external pH 7.5, the
      pH value inside the E1ATP-binding site is 6.95 +/- 0.18. In addition, FITC
      fluorescence quenching by anti-fluorescein and by iodide choline indicated the
      limited access of water into the small pocket of the E1ATP-binding site.

PMID- 9920762
TI  - Isolation, pharmacology and gene organization of KPSFVRFamide: a neuropeptide
      from Caenorhabditis elegans.
AB  - To date, 53 peptides with C-terminal RFamides have been identified by the genome
      sequencing project in the nematode, Caenorhabditis elegans. In this study the
      FMRFamide-related peptide (FaRP) KPSFVRFamide (879.90 Da [MH]+) was structurally
      characterized from extracts of the nematode, Caenorhabditis elegans. Two copies
      of KPSFVRFamide are encoded by a gene designated flp-9. RT-PCR identified a
      single cDNA product which was confirmed as flp-9 by sequence determination. Flp-9
      cDNA was isolated from larval stages of C. elegans but was not detected in adult
      worms, indicating that its expression is may be developmentally regulated.
      KPSFVRFamide displays sequence homology to the nematode peptide, KPNFIRFamide
      (PF4). The physiological effects of KPSFVRFamide, PF4 and the chimeras,
      KPNFVRFamide and KPSFIRFamide, were measured on body wall muscle and the vagina
      vera of the parasitic nematode, Ascaris suum. KPNFVRFamide and KPNFIRFamide had
      Cl--dependent inhibitory activity on innervated and denervated muscle
      preparations, whereas KPSFVRFamide and KPSFIRFamide did not elicit a detectable
      physiological effect. Although all 4 peptides had inhibitory effects on the
      vagina vera, KPSFVRFamide and KPSFIRFamide (threshold, >/=0.1 microM) were less
      potent than KPNFVRFamide and KPNFIRFamide (threshold, >/=10 nM).

PMID- 9920763
TI  - Induction of nitric oxide synthase mRNA by shear stress requires intracellular
      calcium and G-protein signals and is modulated by PI 3 kinase.
AB  - We have investigated the signaling pathways by which shear stress induces
      accumulation of endothelial nitric oxide synthase (eNOS) mRNA in bovine aortic
      endothelial cells (BAEC). Steady laminar fluid shear stress (20 dyn/cm2) induced
      a time-dependent increase in eNOS mRNA levels that did not require de novo
      protein synthesis and was in part transcriptional. Shear responsiveness was
      conferred on a luciferase reporter by a portion of the eNOS gene promoter
      encoding the 5'-flanking region between nt -1600 and -779. Shear-mediated
      induction of eNOS mRNA was abolished by chelation of intracellular calcium
      ([Ca2+]i) with BAPTA-AM, and inhibited by blockade of calcium entry with
      SKF96535. In contrast, eNOS mRNA upregulation by shear was potentiated by
      thapsigargin-mediated depletion of Ca2+i stores. Pertussis toxin (PTX) inhibited
      both the shear-induced elevation in [Ca2+]i and the subsequent increase in eNOS
      mRNA, implicating a PTX-sensitive G-protein in both responses. Shear-induced
      upregulation of eNOS mRNA was unaffected by the calmodulin inhibitor W-7 and by
      the tyrosine kinase inhibitor herbimycin A, suggesting that neither calmodulin
      nor tyrosine kinases are required. However, eNOS mRNA upregulation was
      potentiated by the PI 3-kinase inhibitors wortmannin and LY294002, suggesting
      that PI 3-kinase inhibits the shear response. Although microtubule integrity is
      required for the shear-induced regulation of endothelin-1 mRNA and the
      morphological and cytoskeletal responses to flow, neither microtubule dissolution
      with nocodazole nor microtubule stabilization with taxol altered shear-induced
      [Ca2+]i elevation or upregulation of eNOS mRNA. In conclusion, shear stress of
      BAEC increases eNOS transcriptional rate and upregulates eNOS mRNA levels by a
      process that requires calmodulin-independent [Ca2+]i signaling and a PTX
      sensitive G-protein, is inhibited by PI 3-kinase, and is independent of
      microtubule integrity and tyrosine kinase activity.

PMID- 9920764
TI  - Effect of insulin on farnesyltransferase gene transcription and mRNA stability.
AB  - Recently, we have shown that hyperinsulinemia increases the activity of
      farnesyltransferase (FTase) in vitro (1) and in hyperinsulinemic animals (2),
      stimulates the phosphorylation of the FTase alpha-subunit (3), increases the
      amounts of cellular farnesylated p21Ras (4), and potentiates the nuclear effects
      of other peptide growth factors, such as EGF, IGF-1 and PDGF (5). To further
      investigate the mechanism by which insulin stimulates FTase activity we tested
      the effect of insulin on the rate of FTase transcription, the rate of FTase mRNA
      degradation, and the amounts of FTase protein. Insulin increased the amounts of
      FTase alpha- and beta-subunit mRNA in 3T3-L1 fibroblasts 2.5-fold to 4-fold after
      6 h and 24 h incubation, respectively, but did not increase the rate of FTase
      transcription over a 24 h period. Insulin did, however, increase the stability of
      both alpha- and beta-subunit mRNA. The half-life for both FTase alpha- and beta
      subunit mRNA was approximately 3 h and 6h in the absence and in the presence of
      insulin, respectively. Although insulin stabilized the alpha- and beta-subunit
      mRNA of FTase, there was no increase in amounts of protein of either subunit.
      These data suggest that although insulin increases the stability of the FTase
      mRNA, it stimulates FTase enzymatic activity only at the post-translational
      level.

PMID- 9920765
TI  - Molecular and functional evidence for calcineurin-A alpha and beta isoforms in
      the osteoclast: novel insights into cyclosporin A action on bone resorption.
AB  - We provide the first molecular evidence for the presence of a functional
      serine/threonine phosphatase, calcineurin-A (CN-A), in the osteoclast. Polymerase
      chain reaction (PCR) of an osteoclast cDNA library, together with restriction
      mapping, revealed two isoform sequences, alpha and beta. We then examined the
      functionality of the detected CN-A by assessing the effect of a classical
      antagonist, cyclosporin A (CsA), in the osteoclast resorption (pit) assay. CsA
      (0.1 and 1 microg ml-1) potently inhibited bone resorption. The presence of
      lymphocytes, with or without prior exposure to CsA in vivo, failed to reverse the
      CsA-induced resorption-inhibition. Expectedly, CsA had no direct effect on
      cytosolic Ca2+ levels in fura-2-loaded osteoclasts. These studies are a prelude
      to further investigations into the possible role of CN-A in osteoclast
      regulation. Finally, mechanistic studies on the bone effects of CsA, a widely
      used immunosupressant, should proceed from these observations.

PMID- 9920766
TI  - Functional divergence of the plastid and cytosolic forms of the 54-kDa subunit of
      signal recognition particle.
AB  - Chloroplast and cytoplasmic signal recognition particles (cpSRP and cySRP) each
      contain a similar subunit, SRP54. The chloroplast homologue binds to cpSRP43,
      which is absent from cytosolic SRP, and cySRP54 binds to SRP-RNA, which appears
      to be absent from cpSRP. In the presence of cpSRP43, cpSRP54 posttranslationally
      forms a soluble targeting intermediate, transit complex, with the major light
      harvesting protein of the thylakoid membrane. In contrast, cySRP54 functions
      cotranslationally. In this study we investigated whether cytosolic and
      chloroplast forms of SRP54 were interchangeable in three types of functional
      assays: complementation of an Escherichia coli SRP54 mutant, formation of the
      transit complex, and heterologous binding between the SRP54 subunits, cpSRP43,
      and SRP-RNA. In no cases were the 54-kDa subunits able to substitute for each
      other suggesting that the two proteins are fundamentally different.

PMID- 9920767
TI  - Basic fibroblast growth factor induces cyclooxygenase-2 expression in endothelial
      cells derived from bone.
AB  - Although histological studies have suggested that endothelial cells in bone
      (BDECs) are associated with some osteolytic bone diseases, it is still unclear
      how BDECs contribute to bone remodeling. Here we examined the response of BDECs
      to basic fibroblast growth factor (bFGF, FGF-2) using primary and cloned murine
      BDECs isolated from the femurs of BALB/c mice. Treatment of primary and cloned
      BDECs with bFGF induced cyclooxygenase-2 (COX-2) mRNA and protein expression.
      Furthermore, bFGF promotes the production of prostaglandin E2 (PGE2), which is
      known to be a potent stimulator of bone resorption and to induce osteoclast
      formation. Because the secretion of PGE2 was suppressed by COX-2 specific
      inhibitor NS-398 and by COX-2 antisense oligodeoxynucleotides, bFGF promotes the
      synthesis of PGE2 in a COX-2-dependent manner. Therefore, endothelial cells in
      bone are associated with bone remodeling by controlling COX-2 expression and
      consequently PGE2 production.

PMID- 9920768
TI  - Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce
      hsp70 and hsp27 expression.
AB  - MG132 and lactacystin, two 26S proteasome-specific protease inhibitors, can
      upregulate heat-shock gene transcription without heat shock. In this study, we
      showed that both of these inhibitors induce hyperphosphorylation and DNA-binding
      activity of HSF1 in the absence of heat shock (at 37 degreesC). Since
      trimerization of HSF1 is known to precede the acquisition of HSF1-DNA binding
      activity, it seems that MG132- and lactacystin-induced hyperphosphorylation of
      HSF1 causes conformational changes of HSF1 molecules at 37 degreesC and
      subsequently triggers its trimerization. Inhibition of protein synthesis by
      cycloheximide abolished the MG132- or lactacystin-induced hyperphosphorylation
      and DNA-binding activity of HSF1. These data suggest that the activity of a
      putative kinase(s) targeting HSF1 is upregulated in the presence of MG132 or
      lactacystin. The upregulation of the kinase activity requires de novo protein
      synthesis and is likely due to the inhibition of protein degradation of a short
      lived, kinase(s) targeting HSF1 and/or the cofactor(s) for the kinases, through
      the ubiquitin-proteasome pathway.

PMID- 9920769
TI  - Galphaolf identification by RT-PCR in purified normal pancreatic B cells and in
      islets from rat models of non-insulin-dependent diabetes.
AB  - Recent reports using immunohistochemistry have shown that Galphaolf which shares
      88% homology with Galphas was expressed in pancreatic islets. To test the
      specificity of the expression of this G protein isotype in rat islet cells, B and
      non-B cells were separated by flow cytometry. The expression of Galphaolf and
      adenylyl cyclases (AC) of types II, III, V, and VI was evaluated by reverse
      transcriptase polymerase chain reaction (RT-PCR). Since alterations in the
      expression of AC III were recently reported in the GK rat (a model of non-insulin
      dependent diabetes mellitus, NIDDM), we also have analyzed the mRNA expression of
      Galphaolf and AC isoforms in pancreatic islets from GK rats and from adult rats
      neonatally treated by streptozotocin (nSTZ rats), another model of NIDDM.
      Southern blots of amplicons generated with specific primers of Galphaolf revealed
      the presence of a 540-bp band only in B cells. AC of types II, III, V, and VI
      were expressed both in B and non-B cells. However, AC III mRNA was clearly more
      abundant in non-B than in B cells. Moreover, in B cells the expression of AC VI
      was higher than that of AC V, whereas equal expressions of AC V and AC VI were
      found in non-B cells. In GK rat islets, the mRNA expressions of Galphaolf, AC II,
      and AC III were clearly increased and no change in AC V and AC VI was found. In
      nSTZ rat islets, Galphaolf expression was barely detectable, but AC II and AC III
      mRNA levels were higher than those observed in controls. In conclusion, Galphaolf
      mRNA appeared specifically expressed in islet B cells and was increased in GK
      islets. The steady-state mRNA levels of AC II and AC III were clearly increased
      in the islets of the two rat models of NIDDM. Thus, alterations in the expression
      of G protein isotypes and AC isoforms could contribute to the diabetic phenotype.

PMID- 9920770
TI  - Identification of a novel seven-transmembrane receptor with homology to
      glycoprotein receptors and its expression in the adult and developing mouse.
AB  - Using a PCR-based cloning strategy we have isolated a cDNA from mouse brain and
      named it fex, because it codes for a novel putative G protein-coupled receptor
      expressed in follicles. The deduced amino acid sequence shows a higher degree of
      homology to the family of glycoprotein receptors, namely those for FSH, LH, and
      TSH, than to other G protein-coupled receptors. With 18 leucine-rich repeats FEX
      exhibits features in its N-terminal portion characterizing it as unique within
      the glycoprotein receptor family. In the adult mouse fex expression was detected
      in the male and female gonads, the adrenal medulla, and the olfactory bulb of the
      brain. During embryonic development fex transcripts were detected transiently in
      various tissues, particularly in selected regions of the central nervous system,
      the developing face, the intervertebral discs anlagen, and the limb buds. Because
      fex was expressed during periods of active morphogenesis, it may be an important
      receptor for signals controlling growth and differentiation of specific embryonic
      tissues.

PMID- 9920771
TI  - Cross-linked telomere-protein complexes from chicken erythrocyte nuclei:
      isolation by a new procedure.
AB  - DNA-protein cross-linkages were produced in intact nuclei of chicken erythrocytes
      by the action of cis-diammine dichloroplatinum. The telomeric DNA-protein cross
      linked complexes were then isolated by hybridization with a biotinylated
      oligonucleotide and selective binding on immobilized streptavidin. Two main
      nonhistone proteins were present in the purified complexes, migrating in SDS-gel
      electrophoresis with apparent molecular masses of 66 and 58 kDa, respectively.
      Although the identity of these two proteins is still unknown, it is significant
      that two proteins with similar electrophoretic behavior have been described as
      constituents of the human telomeric complexes. This procedure could also be
      applied to the isolation of DNA-protein cross-linked complexes containing any
      chosen DNA sequence.

PMID- 9920772
TI  - Lactation-dependent expression of an mRNA splice variant with an exon for a
      multiply O-glycosylated domain of mouse milk fat globule glycoprotein MFG-E8.
AB  - Expression of mRNA encoding MFG-E8, a milk fat-associated glycoprotein was
      investigated in mouse mammary gland. Two forms of mRNA, long and short variants,
      were shown to be expressed in the mammary tissue by RT-PCR analysis. Sequence
      analyses of these two variants and an isolated MFG-E8 gene segment indicated that
      the long and short mRNA variants resulted from an alternative splicing of a
      single pre-mRNA through in-flame inclusion and skipping of one exon, which
      encodes a proline/threonine (Pro/Thr)-rich domain. The long variant was expressed
      predominantly in mammary gland and the expression level was remarkably increased
      at late gestation and kept high during lactation. On the contrary, the short
      variant was detected ubiquitously in various tissues and its expression in the
      mammary gland was rather decreased in a lactation dependent manner. Expression of
      the long variant was also detected in a mouse mammary epithelial cell line, COMMA
      1D, and enhanced by incubation with lactogenic hormones. Glycosylation inhibition
      analyses using tunicamycin and alpha-benzyl-GalNAc were conducted with COS7 cells
      transfected with plasmids expressing each mRNA variant, demonstrating that a
      fully glycosylated product of the long mRNA variant was not only N-glycosylated
      but also multiply O-glycosylated, whereas a product of the short one had only N
      glycan(s). These results suggest that the alternative splicing plays a critical
      role for the mammary-specific and lactation-dependent expression of the MFG-E8
      isoform and that the multiply O-glycosylated Pro/Thr-rich domain of this isoform
      is functionally important for formation of milk fat globules in mammary
      epithelial cells.

PMID- 9920773
TI  - Cloning, sequencing, and developmental expression levels of a novel glutamate
      gated chloride channel homologue in the parasitic nematode Haemonchus contortus.
AB  - Glutamate-gated chloride channels (GluCls) are the proposed site of action for
      macrocyclic lactone anthelminthics such as ivermectin (IVM) and the milbemycins
      such as moxidectin (MOX). The importance of this interaction between macrocyclic
      lactones and GluCls is strengthened by the recent genetic evidence that GluCls
      are involved in IVM and MOX resistance in the parasitic nematode Haemonchus
      contortus (1). We have cloned two full length GluCl putative alpha-subunit cDNAs
      from H. contortus (HcGluCla and b) that exhibit different sized ligand binding
      domains. Phylogenetic analysis of the conserved regions of the amino acid
      sequence of HcGluCla suggests that it is a member of the GluCl family but forms a
      distinct subbranch within this family. The expression level of HcGluCla was
      examined in different developmental stages of H. contortus (eggs, L3, and adults)
      and found to be significantly downregulated in eggs compared to adults.

PMID- 9920774
TI  - Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte
      stimulating factor precursor and Is a multifunctional proteoglycan with potential
      growth-promoting, cytoprotective, and lubricating properties in cartilage
      metabolism.
AB  - We have performed cDNA sequencing and homology analyses to elucidate the complete
      amino acid composition for a superficial zone protein (SZP) from human and bovine
      cartilage which has previously been shown to be a proteoglycan specifically
      synthesized by chondrocytes located at the surface of bovine articular cartilage
      and also some synovial lining cells. The results of this study indicate that
      cartilage SZP is homologous with a glycoprotein first described as the precursor
      protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and
      analyses indicate that (i) the amino acid composition of SZP is highly conserved
      between bovine and human species, (ii) SZP contains structural motifs at the N-
      and C-termini which are similar to those found in vitronectin and which may
      impart cell-proliferative and matrix-binding properties to the molecule, and
      (iii) SZP contains large and small mucin-like repeat domains composed of the
      sequences KEPAPTTT/P (76-78 repeats) and XXTTTX (6-8 repeats), respectively,
      which occur within a large central region of approximately 940 amino acids. The
      mucin-like domains are likely to be substituted with O-linked oligosaccharides
      which would impart lubricating properties to SZP which in part accumulates at the
      articular cartilage-synovial fluid interface. Additionally, we have shown that
      interleukin-1 inhibits the biosynthesis of chondrocyte SZP, while TGF-beta and
      IGF-1 increase its biosynthesis, and that in pathological (osteoarthritic) human
      articular cartilage SZP mRNA can be expressed as an alternatively spliced variant
      lacking exons 4 and 5 which encode a potential heparin binding domain. The
      occurrence of different SZP alternative splice variants and the differential
      expression of SZP in the presence of cytokines and growth factors suggest that
      SZP may play an important cytoprotective role by preventing cellular adhesion to
      the articular cartilage surface in normal cartilage metabolism. Modifications to
      the structure of SZP, coupled with inhibition of SZP synthesis during
      inflammation, may account for the attachment and invasion of pannus observed in
      inflammatory joint diseases.

PMID- 9920775
TI  - A PEA3 site flanked by SP1, SP4, and GATA sites positively regulates the
      differentiation-dependent expression of Brachyury in embryonal carcinoma P19
      cells.
AB  - The promoter sequence of Brachyury was analyzed in mouse embryonal carcinoma P19
      cells. The sequence up to -267 bp relative to the transcription start site was
      sufficient to enhance reporter gene expression depending on the mesodermal
      differentiation of P19 cells. Footprint analysis by nuclear extract showed
      binding of a GATA protein and SP4 and mutation of their sites reduced reporter
      gene expression. Gel-retardation assay in the presence of a series of double
      stranded DNA fragments as the competitors showed SP1 and Est sites additionally.
      Deletion of either sites reduced the reporter gene expression, showing that they
      are cooperative. Depletion of PEA3 (a transcription factor of the Est family)
      with a specific antibody diminished the retarded bands only for the nuclear
      extract from differentiated P19 cells. Thus, the PEA3 site supported by SP1, SP4,
      and GATA sites positively regulates the differentiation-dependent expression of
      Brachyury in P19 cells.

PMID- 9920776
TI  - Molecular cloning of a full-length cDNA for human type 3 adenylyl cyclase and its
      expression in human islets.
AB  - The GK (Goto-Kakizaki) rat is a lean model of type 2 diabetes in which the
      diabetic state was spontaneously induced. We recently demonstrated the presence
      in GK rats of two functional point mutations in the promoter region of the type 3
      adenylyl cyclase (AC3) gene that resulted in overexpression of AC3 mRNA
      associated with increased cAMP generation. The AC3 gene promoter mutations are
      the first molecular changes to be described in any specific gene in the GK rat.
      Here we report cloning of a full-length cDNA encoding human AC3 from a human
      fetal brain cDNA library using a PCR-based screening method. This 4142-bp cDNA
      predicts an open reading frame encoding 1144 amino acids containing putative 12
      transmembrane-spanning domains which are typically found in other mammalian AC
      isoforms. Comparison of the translated amino acid sequence of the AC3 gene
      between human and rat shows 95% homology. Using RT-PCR, clear AC3 expression was
      detected in isolated human islets as well as a cDNA panel containing templates
      from eight different tissues (brain, heart, kidney, liver, lung, pancreas,
      placenta, and skeletal muscle). This wide distribution of AC3 expression may
      involve a number of physiological and pathophysiological metabolic processes.

PMID- 9920777
TI  - Extent and limitation of the control of nuclear apoptosis by DNA-fragmenting
      factor.
AB  - During apoptosis, changes to the nucleus of the dying cell include DNA
      degradation and structural collapse. These changes are accomplished by caspase
      mediated cleavage of DNA-fragmenting factor DFF45, an inhibitor of the effector
      molecule DFF40. DFF45 and, more efficiently, a mutant lacking one caspase
      cleavage site (DFF45m) inhibited nuclear changes in a cell-free system when
      apoptosis was initiated by adding caspase-3 to cell extracts. In primary tissues
      from several mammalian species, human caspase-3 activated and human DFF45m
      blocked nuclear apoptosis demonstrating evolutionary conservation of this step.
      However, DFF45m did not significantly inhibit DNA-fragmenting activity in
      extracts from staurosporine-treated cells from the human cell line Jurkat. In
      extracts from normal Jurkat cells, DFF45m blocked caspase-triggered DNA cleavage
      efficiently only if added within a short time of the addition of the caspase. At
      later time points, this inhibition by DFF45m was strongly reduced in efficiency
      while Zn2+ still completely blocked DNA fragmentation. These results demonstrate
      the evolutionary conservation of a linear pathway in apoptosis and suggest the
      existence of more complex events as final effector machinery.

PMID- 9920778
TI  - Imbalanced expression of the glucocorticoid receptor isoforms in cultured
      lymphocytes from a patient with systemic glucocorticoid resistance and chronic
      lymphocytic leukemia.
AB  - The human glucocorticoid receptor (GR) is expressed as two alternatively spliced
      isoforms, GRalpha and GRbeta. Whereas GRalpha is a hormone-activated
      transcription factor, GRbeta does not bind glucocorticoids (GCs), is
      transcriptionally inactive, and is a potential inhibitor of activated GRalpha.
      Differential expression of GR isoforms may play a role in generalized or tissue
      specific GC resistance. GCs induce apoptosis in neoplastic lymphoid cells; and,
      defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia
      (CLL). We studied a patient with generalized GC resistance and CLL. GR number in
      the patient's transformed lymphocytes was approximately one half that of control
      cells with a approximately 10-fold reduction in binding affinity for
      dexamethasone. In vitro apoptosis induction in CLL cells was delayed in response
      to GCs, but not to other apoptosis inducers. Sequencing of the GR cDNA and gene
      including the 2.3-kb coding region, the intron/exon junctions, the known 5'
      regulatory region, and approximately 300 bp of the 3'-region revealed no
      alterations. Western blot with an N-terminal antibody showed normal levels of
      immunoreactive GR, but quantitative analysis with isoform-specific C-terminal
      antibodies revealed a markedly reduced GRalpha expression, and high GRbeta
      expression. These findings indicate that imbalanced expression of the GR isoforms
      may be a mechanism of GC resistance, and may have implications for tumorigenesis
      by enhancing cell survival.

PMID- 9920779
TI  - c-fos induction by heat, arsenite, and cadmium is mediated by a heat shock
      element in its promoter.
AB  - c-fos mRNA is induced by many types of noxious stimuli that are known to enhance
      transcription mediated by the heat shock element (HSE). Nonetheless, it has been
      accepted that the c-fos promoter does not contain an HSE. In this report, we
      revealed that the human and rodent c-fos promoters do contain HSEs which are
      highly responsive to heat, arsenite, and cadmium. These HSEs may play important
      roles in regulating c-fos expression in various pathological and physiological
      situations.

PMID- 9920780
TI  - The hepatitis C virus NS2 protein generated by NS2-3 autocleavage is required for
      NS5A phosphorylation.
AB  - Hepatitis C virus (HCV) is dependent on NS2-3 autocleavage and NS5A
      phosphorylation for its life cycle. We demonstrate that NS5A, when released from
      the NS2-5 polyprotein of the BK virus strain, is phosphorylated as two distinct
      forms, pp56 and pp58. Deletion analysis indicates that the appearance of pp58
      requires NS2 in cis, while pp56 is NS2 independent. Disruption of NS2-3
      autoproteolysis by directed mutagenesis results in loss of pp58. Expression of a
      construct producing NS2-3 is sufficient to restore pp58 in trans. These data
      indicate that generation of functional NS2 via autocleavage of the NS2-3
      precursor and NS5A phosphorylation are consecutive processes, suggesting
      coordinate regulation during virus propagation in vivo.

PMID- 9920781
TI  - A significant role of leptin in the generation of steroid-induced luteinizing
      hormone and prolactin surges in female rats.
AB  - Recent evidence suggests that leptin, the product of obese (ob) gene, may play an
      important role in the regulation of reproductive function. However, a possible
      role of leptin in the preovulatory surges of luteinizing hormone (LH) and
      prolactin (PRL) in rodents has yet to be explored, and thus examined in this
      study. Experiments were performed on both normally fed and 3-day starved rats,
      which were ovariectomized and primed with estradiol and progesterone. At 11:00 h
      on the day of the experiments, normally fed rats received an
      intracerebroventricular injection of artificial cerebrospinal fluid, anti-leptin
      serum, or normal rabbit serum. Three-day starved rats were given artificial
      cerebrospinal fluid or recombinant human leptin (2.5 microgram) via the same
      route. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and
      PRL. The 3-day starvation completely abolished both LH and PRL surges, but leptin
      resumed these hormonal surges to the levels of normally fed rats. In addition,
      anti-leptin serum given to normally fed rats significantly depressed LH surge and
      delayed the onset of PRL surge. This study is the first to demonstrate that
      leptin plays a physiologically important role in the generation of steroid
      induced LH and PRL surges in female rats.

PMID- 9920782
TI  - Increased expression of cyclooxygenases and peroxisome proliferator-activated
      receptor-gamma in Alzheimer's disease brains.
AB  - Recent studies suggest that inflammatory events are associated with plaque
      formation in the brains of patients with Alzheimer's disease (AD). Treatment with
      nonsteroidal anti-inflammatory drugs (NSAIDs) of these patients appears to slow
      the progression of disease. We assessed the occurrence of cyclooxygenases (COX-1
      and -2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in
      temporal cortex from normal and AD brains using specific antibodies. In AD
      brains, protein levels of COX-1 were increased in both cytosolic and particulate
      fractions, and COX-2 protein was also increased in the particulate fraction. On
      the other hand, PPARgamma level was increased in the cytosolic fraction but not
      in the particulate fraction. Thus, expression levels of COX-1, COX-2, and
      PPARgamma may change in AD brains. In addition, several NSAIDs which are also
      PPARgamma activators, such as indomethacin, inhibited COX-2 expression in glial
      cells. These results suggest that PPARgamma activators have inhibitory effects on
      inflammatory events in AD brains.

PMID- 9920783
TI  - Expressions of vascular endothelial growth factor in nonparenchymal as well as
      parenchymal cells in rat liver after necrosis.
AB  - Vascular endothelial growth factor (VEGF) can induce proliferation of sinusoidal
      endothelial cells. Its mRNA expression was increased in proliferating rat
      hepatocytes in primary culture. To clarify a role of VEGF in liver after
      necrosis, expressions of VEGF and its receptors were measured in the liver or
      liver cells isolated from rats after carbon tetrachloride intoxication. Hepatic
      VEGF mRNA expression increased later than 24 h after the intoxication and became
      prominent at 168 h when liver necrosis disappeared, while hepatic mRNA
      expressions of its receptors increased between 24 and 72 h. VEGF mRNA expression
      was increased in Kupffer cells, hepatic macrophages and stellate cells isolated
      from rats between 24 and 72 h after the intoxication and in hepatocytes at 168 h
      compared to those cells from normal rats. Immunohistochemical VEGF stains were
      comparable to such results. Vascular endothelial cells existed abundantly in the
      necrotic areas, and sinusoidal endothelial cells appeared following disappearance
      of the necrotic areas. VEGF mRNA expression in hepatocytes isolated from 70%
      resected liver was increased at 12 h after the operation and became marked
      between 72 and 168 h. Similar increase of hepatic VEGF expression was
      immunohistochemically seen. In conclusion, VEGF derives from nonparenchymal as
      well as parenchymal cells in rat liver after necrosis. The former might
      contribute to vascular endothelial cell proliferation and the latter to
      sinusoidal endothelial cell regeneration.

PMID- 9920784
TI  - Cloning and characterization of a novel Rab-family gene, Rab36, within the region
      at 22q11.2 that is homozygously deleted in malignant rhabdoid tumors.
AB  - Malignant rhabdoid tumors (MRTs) are rare, pediatric soft-tissue tumors.
      Homozygous deletions at chromosome 22q11.2 are a recurrent cytogenetic
      characteristic of MRTs, an indication that this locus may harbor one or more
      genes conferring tumor-suppressor activity. We constructed a deletion map of the
      relevant part of 22q11.2 from a panel of seven MRT cell lines, and isolated a
      novel gene from the center of the region. As it showed a high degree of sequence
      homology to genes of the Rab family, we designated it Rab36. The protein encoded
      by Rab36 was localized at the Golgi body. Sequencing of Rab36 cDNAs from three
      cell lines that retained at least one allele of this gene revealed no nonsense or
      frameshift mutations. Experiments to induce over-expression of Rab36 by
      transfection to an MRT cell line similarly failed to justify designation of this
      gene as a tumor suppressor that would contribute to tumorigenesis by a loss-of
      function mechanism.

PMID- 9920785
TI  - Ventrally emigrating neural tube cells differentiate into heart muscle.
AB  - A population of ventrally emigrating neural tube cells has been shown to migrate
      along the vagus nerve and contribute to the development of the gastrointestinal
      tract. Since the vagus also goes to the heart, we sought to determine if these
      cells migrated into the heart. Neural tube cells were tagged with replication
      deficient retroviral vectors containing the LacZ gene, to permanently label their
      progeny. The virus was microinjected into the lumen of the caudal hindbrain of
      chick embryos on day 2. Embryos were later processed for the detection of LacZ
      positive cells. Labeled cells were initially confined to the neural tube. Later,
      they migrated in association with the vagus nerve into the heart, where they were
      located in the myocardium. Labeled cells were identified as cardiac muscle cells
      of non-neural crest origin, with specific markers. It is concluded that some
      cardiac muscle cells differentiate from the neural tube cells.

PMID- 9920786
TI  - An homologue of the human 100-kDa protein (p100) is differentially expressed by
      Histoplasma capsulatum during infection of murine macrophages.
AB  - Using differential display reverse transcription-PCR (DDRT-PCR) we have
      identified several sequences that are specifically expressed by Histoplasma
      capsulatum during infection of murine macrophages (MPhi). Here, we report the
      characterization of a clone, pHc12, identified as a differentially expressed gene
      1 hour after infection of MPhi. Screening of a cDNA library of H. capsulatum
      allowed us to isolate a clone, pHc12-E, that contains the complete coding
      sequence. We show that after infection the level of transcription of this gene
      increases about 5 fold. Analysis of its sequence revealed the presence of an open
      reading frame of 890 aa (ORF890) that shares respectively 30 and 33% identity
      with human and Caenorhabditis elegans p100 kD and rat p105 kD co-activator
      proteins. Using the two-dimensional Hydrophobic Cluster Analysis (HCA) method, we
      showed that H. capsulatum ORF890 and p100 kD co-activator proteins are clearly
      related. The H. capsulatum protein consists of a four-fold repeated module
      (domains I to IV) like the p100 kD co-activator proteins, whose three-dimensional
      (3D) structure is related to staphylococcal thermonuclease, followed by a
      modified fifth "hybrid" domain which partially resembles the structure of the
      tudor domain found in multiple copies in the Drosophila melanogaster tudor
      protein. These data strongly suggest that ORF890 is homologous to human p100 kD
      and that this protein, named Hcp100, may play an essential role during infection
      by co-activating the expression of specific genes.

PMID- 9920787
TI  - Inhibition of murine neutrophil serine proteinases by human and murine secretory
      leukocyte protease inhibitor.
AB  - Human secretory leukocyte protease inhibitor (SLPI) is a predominant physiologic
      inhibitor of elastase and cathepsin G, proinflammatory serine proteases released
      by activated neutrophils. In order to fully evaluate the potential pharmacologic
      efficacy of human SLPI in animal models of inflammation, it is critical to know
      the potency of the inhibitor for corresponding proteases from the species of
      interest. In this report, we compare the inhibitory activity of human and murine
      SLPI against elastase and cathepsin G from both species. Human and murine
      neutrophil elastase and cathepsin G display comparable Km values for their
      specific peptide substrates. Murine SLPI inhibits murine neutrophil elastase and
      cathepsin G with Ki values of 5 and 0.12 nM, respectively, while human SLPI
      inhibits the both murine serine proteases with Ki's of 0.02 nM. In contrast,
      murine SLPI inhibits human neutrophil elastase and cathepsin G with Ki values of
      1.4 and 90 nM, respectively, while human SLPI inhibits the proteases with Ki's of
      0.3 and 10 nM, respectively. These results demonstrate species-specific
      variations in the protease inhibitory activities of SLPI. Such variations should
      be considered in the evaluation of the activity of human SLPI in murine
      pharmacologic models.

PMID- 9920788
TI  - Distribution and developmental changes of adenylate kinase isozymes in the rat
      brain: localization of adenylate kinase 1 in the olfactory bulb.
AB  - Changes in the levels of three adenylate kinase isozymes (AK1, AK2, and AK3) in
      the rat brain during development were investigated by immunoblot analysis. The
      levels of AK1 and AK3 of the whole brain increased after birth, while AK2 was
      detected only in the early embryonic period. In the adult rat brain, high levels
      of AK1 were present in the olfactory bulb. Immunohistochemical analysis showed
      that AK1 was found predominantly in the olfactory nerve layer and the glomerular
      layer. In the olfactory bulb, AK1 gene expression was enhanced in the early
      postnatal days, whereas it remained low in the cerebellum during the first 10
      postnatal days. These results suggest that the AK isozymes are involved in
      neuronal maturation and regeneration. The understanding of the physiological
      actions of adenosine and ATP as neurotransmitters/neuromodulaters in the central
      nervous system has improved. ATP and adenosine receptors have been found to be
      widely distributed over the whole brain, although the intra- and extracellular
      metabolism of these compounds has not been well elucidated.

PMID- 9920789
TI  - Stimulation of gastric acid secretion by centrally administered orexin-A in
      conscious rats.
AB  - Orexins are novel neuropeptides that are localized in neurons within the lateral
      hypothalamus and regulate feeding behavior. The lateral hypothalamus also plays
      an important role in the central regulation of gut function. We therefore
      hypothesized that orexins might be involved in the central control of gastric
      acid secretion. To address this question, we examined the effect of central
      injection of orexins on gastric acid secretion in rats. Intracisternal injection
      of synthetic orexin-A but not orexin-B dose-dependently stimulated acid secretion
      while intraperitoneal administration of orexin-A failed to stimulate acid
      secretion. Vagotomy or atropine abolished the action by central orexin-A. These
      data suggest for the first time that orexin-A may act in the brain to stimulate
      gastric acid secretion by modulating the vagal system. Considering its
      stimulatory action on feeding, we hypothesize here that orexin-A is a candidate
      mediator of cephalic phase gastric secretion.

PMID- 9920791
TI  - Transfer of sulfur to biotin from biotin synthase (BioB protein).
AB  - In biotin synthase reactions carried out in vitro, we observed efficient transfer
      of 35S to biotin from partially purified E. coli biotin synthase (product of the
      bioB gene) labelled by biosynthetic incorporation of [35S]-cysteine. Mass
      spectrometry was consistent with covalent alteration of the protein in the assay.
      These results suggest that BioB protein is a reagent, not a catalyst.

PMID- 9920790
TI  - Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a
      Swedish population.
AB  - Cytochrome P450 2C9 (CYP2C9) catalysis the metabolism of important drugs such as
      phenytoin, S-warfarin, tolbutamide, losartan, torasemide, and nonsteroidal anti
      inflammatory drugs. A functional polymorphism of the CYP2C9 gene has been
      described. The variant alleles include CYP2C9*2 having a point mutation in exon 3
      causing an Arg144Cys exchange, and CYP2C9*3 with a point mutation in exon 7
      resulting in an Ile359Leu exchange. Genotyping of these variant forms was carried
      out in 430 Swedish healthy volunteers and three different methods were compared.
      Sequence analysis of the different PCR products revealed that other genes in the
      CYP2C locus were co-amplified in one of the methods applied, whereas the other
      two methods were specific for CYP2C9. The frequencies of the CYP2C9*1, CYP2C9*2
      and CYP2C9*3 alleles in the population examined were found to be 0.819, 0.107,
      and 0.074, respectively. The need for careful evaluation of the genotyping
      procedure by sequence analysis of PCR products is emphasised.

PMID- 9920792
TI  - Carcinoma cell lines resistant for growth inhibition and apoptosis to retinoic
      acid are responsive to 4-hydroxy-phenyl-retinamide: correlation with tissue
      transglutaminase.
AB  - Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the
      growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may
      act through alternative signal transduction pathways. 4-HPR induced cell growth
      inhibition and apoptosis in all RA-sensitive as well as -resistant cells,
      demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase
      activity. A tight correlation between the induction of tissue TGase, the
      inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive
      cell lines. However, basal TGase differed in the different cells, suggesting
      inducibility rather than basal levels as the relevant parameter. In sharp
      contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response
      to 4-HPR for tissue TGase. The wider spectrum of activity of 4-HPR in inhibiting
      cell growth and inducing apoptosis makes it a good candidate for the treatment of
      RA-resistant cancer cells.

PMID- 9920794
TI  - Radiation sensitivity of an Escherichia coli mutant lacking NADP+-dependent
      isocitrate dehydrogenase.
AB  - Ionizing radiation induces the production of reactive oxygen species, which play
      an important causative role in radiation damage. NADP+-dependent isocitrate
      dehydrogenase (ICDH) in Escherichia coli produces NADPH, an essential reducing
      equivalent for the antioxidant system. The protective role of ICDH against
      ionizing radiation in E. coli was investigated in wild-type and ICDH-deficient
      strains. Upon exposure to ionizing radiation, the viability was lower and the
      lipid peroxidation was higher in mutant cells compared to wild-type cells.
      Activities of key antioxidant enzymes such as superoxide dismutase, catalase,
      glutathione reductase, and glucose-6-phosphate dehydrogenase were decreased by
      irradiation in both cells. Results suggest that ICDH plays an important role as
      an antioxidant enzyme in cellular defense against ionizing radiation.

PMID- 9920793
TI  - Isolation, characterization, and distribution of a 24-kDa proteoglycan in the
      urine of cachectic cancer and AIDS patients.
AB  - Substantial weight loss in individuals with AIDS or cancer is associated with a
      poor prognosis and increased mortality. We have isolated and partially
      characterized a proteoglycan (named azaftig) from the urine of a cancer patient
      experiencing weight loss. Furthermore, we have raised a polyclonal antibody to
      azaftig in rabbits and developed a procedure to measure the level of this
      proteoglycan in urine by Western blot. We report the presence of azaftig in the
      urine of cancer and AIDS patients experiencing weight loss, but not in the
      control or weight-stable subjects. The azaftig-like immunoreactivity was present
      in 69.2% (9/13) of patients with weight loss, but only in 27.0% (3/11) of weight
      stable cancer or AIDS patients and none of the control subjects (n = 8).

PMID- 9920795
TI  - Antioxidant agent nimesulid and beta-blocker metoprolol do not exert protective
      effects against rat mitochondrial DNA alterations in adriamycin-induced
      cardiotoxicity.
AB  - Possible protective effects of two therapeutical agents (nimesulid and
      metoprolol) in adriamycin-induced cardiotoxicity were examined in rat
      cardiomyocytes at the mitochondrial DNA (mt DNA) level. Analysis by PCR revealed
      the presence of multiple deletions in a large region of the long arc of mt DNA
      which codes for several important genes involved in oxidative phosphorylation, in
      all animals under drug administration. No differences were found in the frequency
      of defective mt DNA between the animals that received only adriamycin (83%,
      10/12), nimesulid and adriamycin (92%, 13/14), or metoprolol and adriamycin (80,
      12/15) (p = 0.004).

PMID- 9920796
TI  - Roles of acetyl-CoA carboxylase beta in muscle cell differentiation and in
      mitochondrial fatty acid oxidation.
AB  - Acetyl-CoA carboxylase beta is expressed primarily in heart and skeletal muscle,
      where it may play a role in the control of mitochondrial fatty acid uptake and
      oxidation by controlling carnitine-palmitoyl-CoA transferase 1. To investigate
      the relationship between ACC-beta expression and myoblast differentiation, we
      specifically blocked ACC-beta production by expressing an antisense gene to the
      specific N-terminal region of ACC-beta in H9c2 cells. The expression of the
      antisense ACC-beta mRNA retarded cell fusion, myosin formation, and creatine
      kinase induction; all of these parameters are hallmarks of muscle cell
      differentiation. On the other hand, the rate of fatty acid oxidation was not
      affected by the presence or absence of ACC-beta in the cells.

PMID- 9920797
TI  - Oxidation of hypotaurine to taurine with photochemically generated singlet
      oxygen: the effect of azide.
AB  - Hypotaurine is oxidized to taurine by singlet oxygen (1O2) generated with
      methylene blue used as a photosensitizer. The oxidation rate increases in the
      presence of deuterium oxide as expected for the involvement of 1O2. Addition of
      the 1O2 quencher azide also produced an activating effect in contrast with the
      expected inhibition. Azidyl radicals produced by the oxidation of azide by the
      horseradish peroxidase/hydrogen peroxide system stimulate the oxidation of the
      added hypotaurine. It is concluded that azide competes with hypotaurine for 1O2
      generating the azidyl radical which is a strong one-electron oxidant transfer of
      the radical to hypotaurine. The hypotaurine radical is then converted into
      taurine, possibly through the disulfone intermediate. Formation of the sulfonic
      hydroperoxide is the possible intermediate in the absence of azide. The finding
      that the azidyl radical efficiently oxidizes hypotaurine to its metabolic product
      taurine raises the expectation of hypotaurine being a valuable scavenger of
      endogenous and exogenous radicals.

PMID- 9920798
TI  - Stimulation of large-conductance Ca2+-activated K+ channels by Evans blue in
      cultured endothelial cells of human umbilical veins.
AB  - The effect of Evans blue (EB) on large-conductance Ca2+-activated K+ (BKCa)
      channels was investigated in cultured endothelial cells of human umbilical veins.
      In whole-cell configuration, EB (50 microM) reversibly increased the amplitude of
      K+ outward currents (IK). When the patch pipettes were filled with 10 mM EGTA,
      its stimulatory effect on IK was unaltered. Further application of EB in the
      presence of suramin, a blocker of P2-purinergic receptor, or AOPCP, an inhibitor
      of 5'-nucleotidase, still increased IK. However, charybdotoxin (100 nM)
      suppressed EB-induced increase in IK. In inside-out configuration, bath
      application of EB (50 microM) did not change single channel conductance but
      significantly increased the activity of BKCa channels. The EB-induced increase in
      the activity of BKCa channels was independent on internal Ca2+. EB (50 microM)
      shifted the activation curve of BKCa channels to less positive membrane
      potentials by approximately 20 mV. The change in the kinetic behavior of BKCa
      channels caused by EB in these cells is due to an increase in mean open time and
      a decrease in mean closed time. These results indicate that EB can stimulate the
      activity of BKCa channel in endothelial cells. This effect is unrelated to its
      blockade of P2-purinergic receptors or inhibition of 5'-nucleotidase. The direct
      stimulation of these ionic channels by EB may contribute to its effect on
      capillary permeability.

PMID- 9920799
TI  - Solution conformation of ferricytochrome c-551 from Pseudomonas stutzeri
      substrain ZoBell.
AB  - The main chain protons and the majority of side chain protons have been assigned
      for the ferric form of Pseudomonas stutzeri substrain ZoBell (American Type
      Culture Collection 14405) cytochrome c-551. The chemical shifts were compared to
      those for the ferrous protein to determine the pseudocontact shift contribution.
      These observed values were compared to contributions calculated from the atomic
      coordinates of the ferrous cytochrome and an optimized effective room temperature
      g-tensor centered on the paramagnetic ferric iron. The agreement between observed
      and calculated values indicates that the conformations of the two forms are
      highly similar.

PMID- 9920800
TI  - Cell cycle control of reverse transcriptase activity for the yeast
      retrotransposon Ty3.
AB  - Retroviruses and retrotransposons depend on their host cells to complete their
      replication cycles. In many cases, the viral step of reverse transcription is
      blocked when host cells are arrested in their cell cycle and this block is only
      released when the host cell resumes division. It has previously been shown that a
      retrotransposon found in Saccharomyces cerevisiae, Ty3, is unable to produce full
      length double-stranded DNA, the product of reverse transcription, when the host
      cells are arrested in G1. In this study we show that, although Ty3 viruslike
      particles are produced at equivalent levels in arrested and nonarrested cells,
      the reverse transcriptase enzyme is inactive in arrested cells. The enzyme
      activity is restored when the arrested cells are permitted to resume cell
      division. These data suggest that a host factor regulates the activity of Ty3
      reverse transcriptase in the cell cycle, which represents a novel cellular
      control of retroelements.

PMID- 9920801
TI  - Pressure regulation of malic dehydrogenase in reversed micelles.
AB  - Malic dehydrogenase (MDH) studied in water and reversed micelles upon pressure
      application revealed a difference in catalysis. Whereas MDH in water appeared to
      be not sensitive to the pressure increasing, the catalytic activity of MDH in
      reversed micelles showed bell-shaped dependencies both on pressure and surfactant
      hydration degree, w0. The catalytic activity of MDH was found to be maximal under
      moderate pressure equal to 300-500 bar and at w0 approximately 14 with the
      difference between lowest and highest levels of the catalytic activity amounted
      to about 10 times. The work presented demonstrates for the first time the co
      operative effect of reversed micelles and pressure application to malic
      dehydrogenase leading to the enzyme regulation that cannot be realized in aqueous
      solution.

PMID- 9920802
TI  - Targeting of MAL, a putative element of the apical sorting machinery, to
      glycolipid-enriched membranes requires a pre-golgi sorting event.
AB  - The MAL proteolipid is a nonglycosylated polytopic membrane protein with specific
      residence in glycolipid-enriched membrane (GEM) microdomains. MAL has been
      proposed as an element of the machinery for apical transport in polarized
      epithelial cells. Previous work demonstrated that MAL requires its four carboxyl
      terminal amino acids to be targeted to GEMs. In the present work, we have
      engineered MAL with N-glycosylation consensus sequences to delimit the site at
      which commitment of MAL to access into GEMs takes place. Comparison of engineered
      MAL proteins bearing either an intact or a truncated carboxyl terminus revealed
      that whereas the former acquired endo H-sensitive and endo H-resistant mature
      glycosylation, the protein with a deleted carboxyl terminus did not. These
      results indicate that although MAL incorporation into GEMs takes place mainly in
      the Golgi, commitment of MAL to enter GEMs is a pre-Golgi event.

PMID- 9920803
TI  - In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2.
AB  - The SUMO-1 has been identified as a protein that is highly similar to ubiquitin
      and shown to conjugate to RanGAP1, PML, Sp200 and I kappa B alpha. The
      conjugation steps are thought to be similar to those of ubiquitination; and human
      Ubc9, which is homologous to the E2 enzyme for the ubiquitin conjugation step,
      was identified and shown to be necessary for the conjugation of SUMO-1 to its
      target protein. Other essential enzymes involved in this modification, however,
      remain to be clarified. Here we cloned human Sua1 (SUMO-1 activating enzyme) and
      hUba2, which are human homologs of yeast Saccharomyces cerevisiae Aos1 and Uba2,
      respectively. The recombinant proteins, Sua1p and hUba2p, formed a complex. In
      this complex, hUba2 bound SUMO-1 and this complex had the activity of the SUMO-1
      activating enzyme. Furthermore, in an in vitro system, RanGAP1 was modified by
      SUMO-1 in the presence of Sua1p/Uba2p and hUbc9p, showing that the modification
      of SUMO-1 could be catalyzed by two enzyme steps, although ubiquitination usually
      requires three enzyme steps.

PMID- 9920804
TI  - Activation of calcium channels by cAMP in STC-1 cells is dependent upon Ca2+
      calmodulin-dependent protein kinase II.
AB  - Activation of L-type calcium channels in the neuroendocrine, cholecytstokinin
      secreting cell line, STC-1, is vital for secretion of CCK. In the present study,
      the regulation of L-type Ca2+ channels by cAMP and Ca2+ calmodulin dependent
      protein kinase II (CaM-KII) in STC-1 cells was investigated. Exposure to 3
      isobutyl-1-methylxanthine (IBMX) increased intracellular cAMP levels, whole cell
      Ca2+ currents and activated Ca2+ channels in cell-attached membrane patches.
      Furthermore, in Fura-2AM loaded cells, cytosolic Ca2+ levels increased upon
      exposure to IBMX. By contrast, pretreatment of cells with the CaM-KII inhibitor
      KN-62, prevented IBMX activation of Ca2+ channels in cell-attached patches or
      increases in cytosolic Ca2+ levels. Inclusion of the synthetic peptide fragment
      290-309 of CaM-KII, a CaM-KII antagonist, in the pipette solution, blocked the
      activation of whole cell Ca2+ currents upon addition of IBMX. These results
      indicate a unique mechanism of L-type Ca2+ channel activation involving two
      phosphorylation events.

PMID- 9920805
TI  - Expression of adenylyl cyclase subtypes in pancreatic beta-cells.
AB  - Activation of adenylyl cyclase by Gs-coupled receptors for insulinotropic
      hormones such as glucagon-like peptide-1 and pituitary adenylate cyclase
      activating polypeptide plays a critical role in stimulating glucose-induced
      insulin secretion. Despite this important role of insulinotropic hormones in the
      regulation of insulin secretion, little is known about which of the multiple
      subtypes of adenylyl cyclase are expressed in beta-cells. Here we report the use
      of PCR primers designed to amplify all subtypes of adenylyl cyclase from cDNA
      prepared from human and rat islets and from insulin-secreting beta-cell lines.
      PCR products were cloned and sequenced to identify the subtypes of adenylyl
      cyclase amplified. Adenylyl cyclase types V and VI, known to couple to Galphas
      and Gbetagamma in the cAMP signaling pathway, account for all subtypes identified
      in human islets and INS-1 cells and the majority of subtypes in rat islets and
      HIT-T15 cells. These findings indicate that pancreatic beta-cells are
      particularly well suited to transmit signals via Gs-coupled receptors such as
      that for glucagon-like peptide-1.

PMID- 9920806
TI  - The MH1 domains of smad2 and smad3 are involved in the regulation of the ALK7
      signals.
AB  - The biological responses of the transforming growth factor beta (TGF-beta)
      superfamily are induced by activation of a receptor complex and Smad proteins. We
      surveyed the TGF-beta superfamily receptors using the degenerate PCR strategy,
      and found activin receptor-like kinase 7 (ALK7) to be abundantly expressed in
      fetal rat pancreatic islets. ALK7 is also expressed in adult rat islets and
      pancreatic beta-cell-derived MIN6 cells. The constitutively active form of ALK7,
      ALK7(T194D), activated Smad3 and a chimeric Smad protein, Smad3-2, containing the
      MH1 domain of Smad3 and the MH2 domain of Smad2, and translocated them to nuclei
      and then induced activation of the human PAI-1 promoter. However, neither Smad2
      nor Smad2-3 protein, containing the MH1 domain of Smad2 and the MH2 domain of
      Smad3 were activated. These results indicate that the ALK7 signal regulates
      nuclear localization and activation of Smad2 and Smad3, and the MH1 domain of
      Smad2 has inhibitory effects on the nuclear localization.

PMID- 9920807
TI  - Novel sodium binding properties of some cyclopentapeptide endothelin A selective
      receptor antagonists: electrospray and fast-atom-bombardment mass spectrometric
      studies.
AB  - Electrospray ionization and fast atom bombardment mass spectrometric methods
      reveal novel interactions of endothelin A selective receptor antagonists, cyclo(D
      Trp-D-Asp-Pro-D-Val-Leu), cyclo(D-Trp-D-Glu-Ala-D-allo-Ile-Leu) and cyclo(D-Trp-D
      Asp-Pro-D-Ile-Leu) with sodium ions. The peptides have very high intrinsic
      affinities for sodium ions, and form multiple sodium adducts and sandwich
      structures: [M + Na]+, [M + 2Na - H]+, [M + 3Na - 2H]+, [M + 4Na - 3H]+, [M + 5Na
      - 4H]+, [2M + Na]+, [2M + 2Na - H]+, [2M + 3Na - 2H]+, [2M + 4Na - 3H]+, [2M +
      5Na - 4H]+, [2M + 6Na - 5H]+, and [2M + 7Na - 6H]+. The three cyclic peptides
      exhibit similar sodium binding stoichiometries despite differences in their amino
      acids. The observed sodium binding properties may have implications in
      understanding their protective effects against ischemia-induced acute renal
      failure. Those cyclic peptides that offer protection may be those that have high
      affinities for multiple sodium ions.

PMID- 9920808
TI  - Effect of long-term exercise on gene expression of insulin signaling pathway
      intermediates in skeletal muscle.
AB  - To elucidate the molecular mechanism underlying insulin sensitivity, we have
      thought to investigate gene expression of insulin signaling pathway intermediates
      in skeletal muscle from sedentary and endurance-trained rats. Adult male Sprague
      Dawley rats were trained for 9 weeks on a treadmill; 30 m/min at a 6 degrees
      incline, 90 min/day, 5 days/week. The levels of PI 3-kinase, GLUT4, p70 S6 kinase
      and Ras mRNA were significantly increased by 89, 40, 38, and 47%, respectively,
      with running training; however, the Nck mRNA level was decreased by 24%. mRNA
      levels of SHP-2, Grb2, Sos, Shc, GAP, p62 and p90 S6 kinase were unaltered by
      running training. We have previously reported that endurance training increases
      mRNA levels of insulin receptor, IRS-1 and ERK1 in skeletal muscle of rats. Taken
      together, our data suggest that gene expression of the insulin signal pathway
      intermediates is modulated by endurance training that may be associated with
      alteration of insulin sensitivity.

PMID- 9920809
TI  - Activation of stress-activated protein kinases by hepatocyte isolation induces
      gene 33 expression.
AB  - Gene 33 is a putative immediate early gene and we have shown that mRNA encoding
      for gene 33 exhibits a transient increase as a result of the procedures used for
      hepatocyte isolation. The stress-activated protein kinases p46 JNK, p54 JNK, and
      p38 SAPK are activated by hepatocyte isolation and precede changes in gene 33
      mRNA content. Although each SAPK isoform shows a distinctive profile of activity
      during isolation and subsequent hepatocyte culture, in each case the activation
      is transient and is largely reversed within 3 h of hepatocyte isolation. SB
      203580, a p38 SAPK inhibitor, prevents the change to gene 33 expression in
      response to hepatocyte isolation. Given the possible role of gene 33 as an
      immediate early gene, the data presented here have general implications for
      control of hepatocyte proliferation and differentiation.

PMID- 9920810
TI  - 3T3-L1 adipocytes express two isoforms of phospholipase D in distinct subcellular
      compartments.
AB  - Phospholipase D has been implicated as an important enzyme in a range of cellular
      responses, including regulated secretion and the formation of secretory vesicles,
      cell proliferation and control of cell morphology. As insulin treatment of
      adipocytes has been shown to stimulate a phosphatidylcholine-specific
      phospholipase D and also modulates membrane trafficking, we wished to determine
      which isoform(s) of phospholipase D were present within adipocytes, to identify
      their subcellular distribution, and examine how this distribution may change in
      response to insulin. Using RT-PCR, 3T3-L1 adipocytes were found to express two
      isoforms of phospholipase D, specifically PLD1b and PLD2a. Using isoform-specific
      antibodies, PLD1 and PLD2 were found to be present predominantly in intracellular
      membranes, unlike the situation reported in other cells. Detailed analysis of the
      intracellular localisation of PLD1 and PLD2 revealed that these isoforms are
      differentially localised within adipocytes, implying functionally distinct roles
      for PLD activity in distinct subcellular compartments.

PMID- 9920812
TI  - Sequence elements required for apolipoprotein B mRNA editing enhancement activity
      from chicken enterocytes.
AB  - Mammalian intestinal apolipoprotein B (apoB) mRNA edits codon 2153 from CAA in
      apoB100 mRNA to a stop codon (UAA) in apoB48 mRNA. By contrast, chicken
      intestinal apoB mRNA contains a CAA codon at the corresponding site, but is not
      edited. Chicken enterocyte S100 extracts fail to edit mammalian apoB RNA, but
      contain factor(s) which enhance the mammalian enterocytes editing activity. By
      converting the chicken apoB mooring sequences to the conserved mammalian
      sequences, the study confirmed that this 11-nucleotide stretch was necessary and
      sufficient for minimal RNA editing. Using rat and chicken apoB chimeric
      constructs, the study revealed that mammalian apoB sequences were required for
      editing enhancement. In concert with the 29-nucleotide conserved cassette, the 5'
      rat apoB element (nucleotides 6615-6629) increased editing at C-6666, and was
      necessary for editing enhancement of chicken enterocyte S100 extracts. Similarly,
      the 3' rat apoB element (nucleotides 6726-6752) was required for editing
      enhancement of chicken enterocyte S100 extracts, but to a lesser extent in
      efficiency, compared to the 5' region. In conclusion, this study identified the
      sequences required for editing enhancement activity from chicken enterocyte S100
      extracts.

PMID- 9920811
TI  - Resveratrol, a natural product present in wine, decreases tumour growth in a rat
      tumour model.
AB  - Resveratrol administration to rats inoculated with a fast growing tumour (the
      Yoshida AH-130 ascites hepatoma) caused a very significant decrease (25%) in the
      tumour cell content. The effects of this diphenol were associated with an
      increase in the number of cells in the G2/M cell cycle phase. Interestingly, flow
      cytometric analysis of the tumour cell population revealed the existence of an
      aneuploid peak (representing 28% of total), which suggests that resveratrol
      causes apoptosis in the tumour cell population resulting in a decreased cell
      number.

PMID- 9920813
TI  - Environmental upregulation of the atrial natriuretic peptide gene in the living
      fossil, Limulus polyphemus.
AB  - Northern blot analysis revealed that atrial natriuretic peptide (ANP) gene
      expression occurs in heart, hematocytes and gills of the invertebrate Limulus
      polyphemus, the horseshoe crab. In low salinity and on land ANP prohormone
      messenger RNA in Limulus' heart was 32-fold less compared to that in a vertebrate
      heart (i.e., rat, Rattus norvegicus). ANP gene expression doubled (P < 0.05) in
      Limulus' heart and gills with change from land and low salinity to medium
      salinity and osmolality. ANP gene expression was 10-fold higher in Limulus' gills
      in seawater (i.e., high salinity). The products of this ANP gene expression
      (i.e., ANP, long acting natriuretic peptide, vessel dilator and kaliuretic
      peptide) were released and increased in the circulation, i.e., hemolymph, of
      Limulus proportional to the increase in salinity and osmolality (P = <0.01).
      These results suggest that modification of ANP gene expression enables animals to
      adapt to freshwater, seawater, and land.

PMID- 9920814
TI  - Thiazolidinediones suppress endothelin-1 secretion from bovine vascular
      endothelial cells: a new possible role of PPARgamma on vascular endothelial
      function.
AB  - We examined the effect of troglitazone on immunoreactive endothelin-1 (ET-1)
      secretion from cultured bovine vascular endothelial cells (bVECs). Insulin (10(
      9)-10(-7) M) stimulated ET-1 secretion in a dose-dependent fashion without any
      kinetic change. Troglitazone (1-20 microM) dose-dependently inhibited both
      spontaneous and insulin-stimulated ET-1 secretion. This inhibitory effect of
      troglitazone was associated with reduced ET-1 mRNA levels. Addition of
      indomethacin (100 microM) or Nw-nitro-l-arginine methyl ester (1 mM) and
      downregulation of protein kinase C by prolonged pretreatment of the cells with a
      phorbol ester, 12-O-tetradecanoylphorbol 13-acetate, did not affect the
      inhibitory effect of troglitazone at concentrations up to 10 microM. Troglitazone
      did not change the intracellular Ca2+ concentration stimulated by angiotensin II
      (10 microM). Other PPARgamma ligands, pioglitazone (1-10 microM) and 15-deoxy
      delta 12, 14-prostaglandin J2 (1-10 microM), but not a PPARalpha ligand,
      bezafibrate (1-10 microM), dose-dependently suppressed spontaneous ET-1 secretion
      from bVECs. These results, taken together, suggest that troglitazone inhibits ET
      1 mRNA expression and secretion in bVECs possibly through activation of
      PPARgamma. This inhibition may contribute to the hypotensive effect of
      troglitazone in insulin-resistant subjects.

PMID- 9920815
TI  - Oxidative injury induced cyclooxygenase activation in experimental
      hepatotoxicity.
AB  - This report investigates the plasma and/or urinary levels of 8-iso-PGF2alpha, a
      nonenzymatic, and 15-keto-dihydro-PGF2alpha, a cyclooxygenase catalyzed oxidation
      product of arachidonic acid in experimental hepatotoxicity in rats. The study was
      undertaken to evaluate oxidative injury-induced inflammation as a consequence of
      cyclooxygenase induction. A significant and immediate increase of 8-iso-PGF2alpha
      in both plasma and urine after CCl4 administration indicates an oxidative injury
      during acute hepatotoxicity in rats. The inflammatory response index was
      determined by measuring 15-keto-dihydro-PGF2alpha levels in plasma which
      increased significantly 9-fold at 4 h after the administration of CCl4. The
      oxidative injury index, 8-iso-PGF2alpha, in both plasma and urine increased 17-
      and 53-fold, respectively. Six hours later the levels of 15-keto-dihydro
      PGF2alpha in plasma remained high (5-fold increase) when 8-iso-PGF2alpha levels
      in plasma and urine elevated to 7- and 87-fold, respectively. Thus,
      cyclooxygenase and free radical-catalyzed oxidation of arachidonic acid are well
      involved during CCl4-induced hepatotoxicity. Cyclooxygenase-dependent
      inflammatory response through PGF2alpha formation in CCl4-induced hepatotoxicity
      may possibly be a secondary effect to oxidative injury and a conceivable link
      between inflammatory response and oxidative injury.

PMID- 9920816
TI  - Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and
      cardioprotective properties?
AB  - Manganese dipyridoxyl diphosphate (MnDPDP) is a contrast agent for magnetic
      resonance imaging (MRI) of the liver. Aims of the study were to examine if MnDPDP
      possesses superoxide dismutase (SOD) mimetic activity in vitro, and if
      antioxidant protection can be demonstrated in an ex vivo rat heart model.
      Superoxide (*O-2) and hydroxyl radicals (*OH-) were generated in xanthine oxidase
      and Fenton reactions. Spin adducts with 5,5-dimethyl-1-pyrroline-N-oxide were
      detected by electron spin resonance spectroscopy. Contractile function and enzyme
      release were monitored in rat hearts during hypoxia-reoxygenation. Low microM
      concentrations of MnDPDP and its metabolite Mn dipyridoxyl ethylene-diamine
      (MnPLED) dismutated *O-2, but showed no activity in Fenton or catalase reactions.
      MnDPDP 30 microM improved contractile function and reduced enzyme release in rat
      hearts during reoxygenation. It is concluded that MnDPDP and MnPLED possess SOD
      mimetic activities and may thereby protect the heart in oxidative stress.

PMID- 9920817
TI  - Macrophage-inflammatory protein-1alpha regulates preosteoclast differentiation in
      vitro.
AB  - A validated in vitro system was used to investigate the nature of osteoclast
      inducing growth factors (OGF) present in fetal rat calvarial conditioned medium
      (RCCM). Evidence is presented here that macrophage inflammatory protein-1alpha
      (MIP-1alpha), a member of the C-C chemokine family, is an essential factor for
      the induction of osteoclast differentiation in this system. Specific polyclonal
      antibodies against MIP-1alpha significantly inhibited development of TRAP
      positive osteoclast precursors and multinucleated osteoclasts induced by RCCM.
      Anti-MIP-1alpha antibody treatment was accompanied by an increase in the number
      of macrophage-like cells, suggesting that bone-derived MIP-1alpha is involved in
      the direction of preosteoclast formation with an inhibitory action on progenitor
      cell proliferation. Reverse-phase HPLC of RCCM resolved multiple fractions with
      OGF activity. OGF fractions separated at low acetonitrile (AcN) concentrations
      (</=15%) did not bind heparin and were not blocked in their bioactivity by the
      anti-MIP-1alpha antibody. However, OGF fractions eluted at higher AcN
      concentrations (30-70%) showed heparin-binding activity and were inhibited in
      their bioactivity by the anti-MIP-1alpha antibody. Western blotting of RCCM with
      the anti-MIP-1alpha antibody revealed a distinct band with a molecular mass of
      around 8-14 kDa corresponding to MIP-1alpha. Recombinant rat MIP-1alpha dose
      dependently stimulated formation of mononuclear osteoclast precursors with
      maximum stimulation at 50 ng/ml, though it could not fully mimic RCCM activity.
      These results identify MIP-1alpha as a candidate responsible for bone-derived OGF
      bioactivity and confirm that chemokines play an important role in the process of
      osteoclast recruitment and differentiation.

PMID- 9920818
TI  - Identification and characterization of baxepsilon, a novel bax variant missing
      the BH2 and the transmembrane domains.
AB  - The Bax gene is a member of the Bcl2 family that functions to regulate the
      programmed cell death process. A number of Bax isoforms have been previously
      identified: alpha, beta, gamma, delta, and omega. Here we report the
      identification and characterization of an additional Bax variant, termed
      Baxepsilon. The newly identified Bax variant contains a 97-base insertion
      generated by alternative splicing which includes a previously unidentified exon
      between exons 4 and 5. The insertion causes the production of a truncated Bax
      protein, termed Baxepsilon, which encodes a protein of 164 residues with a
      calculated molecular weight of 18 kDa. The last 69 amino acids of Baxalpha that
      encompass the BH2 and the TM domains are missing in Baxepsilon. The Baxepsilon
      protein, when expressed as a GST fusion protein, associated efficiently with
      Baxalpha, Baxepsilon, Bcl2, and Bcl-xL. In addition, Baxepsilon was active in
      inducing apoptosis when tested in a transient transfection assay. Furthermore,
      the presence of antiapoptotic genes including Bcl2, Bcl-xL, and baculovirus p35
      abrogated Baxepsilon and Baxalpha function. Although the newly identified Bax
      variant was detectable by RT-PCR in several normal mouse tissues, the role of
      this variant in controlling programmed cell death is currently unknown.

PMID- 9920819
TI  - The genomic organization of the partial D category DVa: the presence of a new
      partial D associated with the DVa phenotype.
AB  - Within the Rh blood group, the partial D phenotype is a well known RhD variant,
      that induces Rh-incompatible blood transfusion and hemolytic diseases in the
      newborn. The partial D category DVa phenotype (DVa Kou.) results from a hybrid of
      RhD-CE-D transcript. We demonstrated a genomic organization of the hybrid RHD-CE
      D gene leading to the DVa phenotype, and showed that the DVa gene were generated
      from gene conversion between the RHD and the RHCE genes in relatively small
      regions. This study also revealed that the presence of a new partial D associated
      with the DVa phenotype, which we termed the DVa-like phenotype. In this
      phenotype, five RHD-specific nucleotides were replaced with the corresponding
      RHCE-derived nucleotides on the exon 5 of the RHD gene. In addition, two variants
      of the mutated RHD genes at nucleotide 697 were revealed in the RhD variant
      samples. These results will provide useful information for future research into
      the diversification of the Rh polypeptides.

PMID- 9920820
TI  - Telomerase activity does not always imply telomere maintenance.
AB  - The forced expression of the catalytic subunit of human telomerase, hTERT,
      produces telomerase activity, allows telomere maintenance, and extends the
      cellular life span of IMR90 human lung fibroblasts. The mutation D869A abolishes
      both the catalytic activity of hTERT and its ability to extend cellular life
      span, demonstrating that the immortalizing capabilities of the enzyme are
      dependent on active catalysis. A second mutant of hTERT was examined that
      contains three copies of an HA epitope inserted at the C-terminus. This mutant
      produced telomerase activity in fibroblasts that was virtually indistinguishable
      from that of wild type telomerase when assayed in vitro. However, the forced
      expression of this mutant failed to maintain telomeres or extend cellular life
      span. Our results show that the catalytic activity of hTERT is required for
      cellular immortalization but that the presence of active telomerase does not
      necessarily imply telomere maintenance and immortality.

PMID- 9920821
TI  - Proteasome inhibitors induce the association of Alzheimer's amyloid precursor
      protein with Hsc73.
AB  - Amyloid precursor protein (APP) is a secretory membrane-bound protein that
      undergoes restrictive proteolysis and degradation with a short life span in the
      constitutive secretory pathway or in the endosomal/lysosomal compartment. The
      degradation machinery, including cellular trafficking and the restrictive
      cleavage of APP, is poorly understood. To gain further insight into the
      intracellular degradation mechanism of APP, we searched for effector proteins
      that interact with APP. We found that a cytosolic molecular chaperon, Hsc73,
      effectively interacts with the cytoplasmic domain of APP in the presence of
      proteasome inhibitors. Hsc73 binds to the cytoplasmic domain near the post
      transmembrane region of APP and not to the KFERQ-related sequence, KFFEQ, at the
      C-terminal tail that is assumed to be the selective targeting signal for
      lysosomal proteolysis. The amounts of Hsc73 that bind to several APP species such
      as those found in pathological Familial Alzheimer's disease (FAD), Swedish, or
      Dutch type mutation, are almost identical, suggesting that an abnormal
      conformation around the secretory cleavage site or a pathological imbalance in
      APP processing are not irrelevant to the efficiency of Hsc73 binding.

PMID- 9920822
TI  - Structure-activity relationship study of steroidal and nonsteroidal inhibitors of
      the enzyme estrone sulfatase.
AB  - We report the initial results of a series of molecular modelling studies to
      investigate the structural properties of non-steroidal inhibitors required for
      inhibitory activity against the enzyme estrone sulfatase (ES) [the enzyme
      responsible for the conversion of nonactive (sulfated) estrone to the active
      (nonsulfated) estrone]. From the results of the present study, we conclude that
      the C(17) polar group may not be necessary for inhibitory activity and that the
      only requirement appears to be the mimicking of the steroid C(3) sulfonate group.
      To test our hypotheses, we have designed novel straight chain inhibitors based
      upon alkyl alcohols, which upon evaluation, have been shown to possess inhibitory
      activity (e.g., an inhibitor based upon trichloroethanol has been shown to
      possess 46% inhibition at 0.76mM).

PMID- 9920823
TI  - Opposite role of interferon-gamma and interleukin-4 on the regulation of blood
      pressure in mice.
AB  - There is growing evidence that T-lymphocyte dysfunction contributes to the
      development of hypertension. IL-4 and IFN-gamma are important regulators of T
      lymphocyte function. Therefore, we investigated the effect of neutralizing
      antibodies against IL-4 (alpha-IL-4) and IFN-gamma (alpha-IFN-gamma) on the
      development of hypertension in NZBNZWF1 hybrid compared to normotensive NZW
      control mice. Antibody-producing cells were encapsulated and injected
      intraperitoneally in mice at 6,8 and 10 weeks of age. This treatment resulted in
      significant levels of antibody in the serum. At 12 weeks of age blood pressure
      was recorded under anesthesia. Mean arterial blood pressure (MAP) increased in
      NZBNZWF1 hybrids between the age of 6 and 12 weeks. This increase was inhibited
      by treatment with alpha-IL-4, but was not affected by alpha-IFN-gamma. Treatment
      with alpha-IL-4 did not influence MAP in normotensive NZW or C57B1/6J mice.
      However, in these mice, treatment with alpha-IFN-gamma increases MAP. This
      increase in MAP by alpha-IFN-gamma was prevented by simultaneous treatment with
      alpha-IL-4. The present study demonstrates the influence of endogenous IL-4 and
      IFN-gamma on blood pressure.

PMID- 9920824
TI  - Intracellular acidification during apoptosis can occur in the absence of a
      nucleus.
AB  - During apoptosis, DNA fragmentation and intracellular acidification occur
      concurrently. Previous results have shown that intracellular acidification is not
      required for DNA fragmentation, while the alternative, that acidification is a
      consequence of DNA fragmentation was analyzed here. To obviate the requirement of
      any nuclear function in acidification, apoptosis was induced by staurosporine in
      cytoplasts made from the breast tumor cell line MDA-MB-468. Both cells and
      cytoplasts demonstrated externalization of phosphatidylserine that was prevented
      by the pan-caspase inhibitor zVAD-fluoromethylketone or by expression of Bcl-2.
      Intracellular acidification was observed in both cells and cytoplasts and this
      was also inhibited by both zVAD-fluoromethylketone and Bcl-2. These results show
      that intracellular acidification and DNA fragmentation are independent
      consequences of caspase action during apoptosis.

PMID- 9920825
TI  - Problems in Hodgkin's disease management.

PMID- 9920826
TI  - Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate
      autologous, antileukemic T-cell responses.
AB  - We have previously reported that leukemic dendritic cells (DC) can be generated
      ex vivo from myelomonocytic precursors in chronic myelogenous leukemia. In this
      study we report the generation of DC from acute myelogenous leukemia (AML) cells
      and their potent ability to stimulate leukemia-specific cytolytic activity in
      autologous lymphocytes. DC were generated in vitro using granulocyte-macrophage
      colony-stimulating factor +interleukin-4 in combination with either tumor
      necrosis factor-alpha or CD40 ligand (CD40L). Cells from 19 AML patients with a
      variety of chromosomal abnormalities were studied for their ability to generate
      DC. In all but 1 case, cells with the morphology, phenotypic characteristics, and
      T-cell stimulatory properties of DC could be generated. These cells expressed
      high levels of major histocompatibility complex class I and class II antigens as
      well as the costimulatory molecules B7-2 and ICAM-1. In three cases these cells
      were determined to be of leukemic origin by fluorescence in situ hybridization
      for chromosomal abnormalities or Western blotting for the inv(16) fusion gene
      product. Autologous lymphocytes cocultured with AML-derived DC (DC-AL) were able
      to lyse autologous leukemia targets, whereas little cytotoxicity was noted
      against autologous, normal cells obtained from the patients during remission. We
      conclude that leukemia derived DC may be useful for immunotherapy of many AML
      patients.

PMID- 9920827
TI  - Treatment of refractory and relapsed acute myelogenous leukemia with combination
      chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar).
AB  - A potential mechanism of chemotherapy resistance in acute myeloid leukemia (AML)
      is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is
      often overexpressed in myeloblasts from refractory or relapsed AML. In a
      multicenter phase II clinical trial, 37 patients with these poor risk forms of
      AML were treated with PSC 833 (Valspodar; Novartis Pharmaceutical Corporation,
      East Hanover, NJ), a potent inhibitor of the MDR-1 efflux pump, plus
      mitoxantrone, etoposide, and cytarabine (PSC-MEC). Pharmacokinetic (PK)
      interactions of etoposide and mitoxantrone with PSC were anticipated, measured in
      comparison with historical controls without PSC, and showed a 57% decrease in
      etoposide clearance (P =.001) and a 1.8-fold longer beta half-life for
      mitoxantrone in plasma (P <.05). The doses of mitoxantrone and etoposide were
      substantially reduced to compensate for these interactions and clinical toxicity
      and in Cohort II were well tolerated at dose levels of 4 mg/m2 mitoxantrone, 40
      mg/m2 etoposide, and 1 g/m2 C daily for 5 days. Overall, postchemotherapy marrow
      hypoplasia was achieved in 33 patients. Twelve patients (32%) achieved complete
      remission, four achieved partial remission, and 21 failed therapy. The PK
      observations correlated with enhanced toxicity. The probability of an infectious
      early death was 36% (4 of 11) in patients with high PK parameters for either drug
      versus 5% (1 of 20) in those with lower PK parameters (P =.04). P-gp function was
      assessed in 19 patients using rhodamine-123 efflux and its inhibition by PSC. The
      median percentage of blasts expressing P-gp was increased (49%) for leukemic
      cells with PSC-inhibitable rhodamine efflux compared with 17% in cases lacking
      PSC-inhibitable efflux (P =.004). PSC-MEC was relatively well tolerated in these
      patients with poor-risk AML, and had encouraging antileukemic effects. The
      Eastern Cooperative Oncology Group is currently testing this regimen versus
      standard MEC chemotherapy in a phase III trial, E2995, in a similar patient
      population.

PMID- 9920828
TI  - Apoptotic role of Fas/Fas ligand system in the regulation of erythropoiesis.
AB  - The possible involvement of Fas and Fas ligand (FasL) in the regulation of
      erythropoiesis was evaluated. Immunohistochemistry of normal bone marrow
      specimens revealed that several immature erythroblasts undergo apoptosis in vivo.
      Analysis of bone marrow erythroblasts and purified progenitors undergoing
      unilineage erythroid differentiation showed that Fas is rapidly upregulated in
      early erythroblasts and expressed at high levels through terminal maturation.
      However, Fas crosslinking was effective only in less mature erythroblasts,
      particularly at basophilic level, where it induced apoptosis antagonized by high
      levels of erythropoietin (Epo). In contrast, FasL was selectively induced in late
      differentiating Fas-insensitive erythroblasts, mostly at the orthochromatic
      stage. FasL is functional in mature erythroblasts, as it was able to kill Fas
      sensitive lymphoblast targets in a Fas-dependent manner. Importantly, FasL
      bearing mature erythroblasts displayed a Fas-based cytotoxicity against immature
      erythroblasts, which was abrogated by high levels of Epo. These findings suggest
      the existence of a negative regulatory feedback between mature and immature
      erythroid cells, whereby the former cell population might exert a cytotoxic
      effect on the latter one in the erythroblastic island. Hypothetically, this
      negative feedback operates at low Epo levels to moderate the erythropoietic rate;
      however, it is gradually inhibited at increasing Epo concentrations coupled with
      enhanced erythrocyte production. Thus, the interaction of Fas and FasL may
      represent an apoptotic control mechanism for erythropoiesis, contributing to the
      regulation of red blood cell homeostasis.

PMID- 9920830
TI  - Prolonged expression of c-fos suppresses cell cycle entry of dormant
      hematopoietic stem cells.
AB  - The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic
      stem (Lin-Sca-1(+)) cells stimulated with stem cell factor, interleukin-3 (IL-3),
      and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used
      bone marrow (BM) cells from transgenic mice carrying the c-fos gene under the
      control of the interferon-alpha/beta-inducible Mx-promoter (Mx-c-fos), and fetal
      liver cells from c-fos-deficient mice. Prolonged expression of the c-fos in Lin
      Sca-1(+) BM cells inhibited factor-dependent colony formation and hematopoiesis
      on a stromal cell layer by keeping them at G0/G1 phase of the cell cycle. These
      Lin-Sca-1(+) BM cells on a stromal layer entered into the cell cycle whenever
      exogenous c-fos was downregulated. However, ectopic c-fos did not perturb colony
      formation by Lin-Sca-1(+) BM cells after they entered the cell cycle.
      Furthermore, endogenous c-fos is not essential to cell cycle progression of
      hematopoietic stem cells because the factor-dependent and the stroma-dependent
      hematopoiesis by Lin-Sca-1(+) fetal liver cells from c-fos-deficient mice was not
      impaired. These results suggest that the c-fos induced in primitive hematopoietic
      stem cells negatively controls cell cycle progression and maintains them in a
      dormant state.

PMID- 9920829
TI  - Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular
      cloning of the mouse OSM receptor beta subunit.
AB  - Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines
      that share the gp130 receptor subunit. Of these family members, leukemia
      inhibitory factor (LIF) is most closely related to OSM, and various overlapping
      biologic activities have been described between human LIF and OSM (hLIF and
      hOSM). Two types of functional hOSM receptors are known: the type I OSM receptor
      is identical to the LIF receptor that consists of gp130 and the LIF receptor beta
      subunit (LIFRbeta), and the type II OSM receptor consists of gp130 and the OSM
      receptor beta subunit (OSMRbeta). It is thus conceivable that common biologic
      activities between hLIF and hOSM are mediated by the shared type I receptor and
      OSM-specific activities are mediated by the type II receptor. However, in
      contrast to the human receptors, recent studies have demonstrated that mouse OSM
      (mOSM) does not activate the type I receptor and exhibits unique biologic
      activity. To elucidate the molecular structure of the functional mOSM receptor,
      we cloned a cDNA encoding mOSMRbeta, which is 55.5% identical to the hOSMRbeta at
      the amino acid level. mOSM-responsive cell lines express high-affinity mOSM
      receptors, as well as mOSMRbeta, whereas embryonic stem cells, which are
      responsive to LIF but not to mOSM, do not express mOSMRbeta. mOSMRbeta alone
      binds mOSM with low affinity (kd = 13.0 nmol/L) and forms a high-affinity
      receptor (kd = 606 pmol/L) with gp130. Ba/F3 transfectants expressing both
      mOSMRbeta and gp130 proliferated in response to mOSM, but failed to respond to
      LIF and human OSM. Thus, the cloned mOSMRbeta constitutes an essential and
      species-specific receptor component of the functional mOSM receptor. Reminiscent
      of the colocalization of the mOSM and mLIF genes, the mOSMRbeta gene was found to
      be located in the vicinity of the LIFRbeta locus in the proximal end of
      chromosome 15.

PMID- 9920831
TI  - HCA, an immunoglobulin-like adhesion molecule present on the earliest human
      hematopoietic precursor cells, is also expressed by stromal cells in blood
      forming tissues.
AB  - We have previously shown that the HCA/ALCAM (CD166) glycoprotein, a member of the
      immunoglobulin family that mediates both homophilic and heterophilic cell-cell
      adhesion, via the CD6 ligand, is expressed at the surface of all of the most
      primitive CD38(-/lo), Thy-1(+), rho123(lo), CD34(+) hematopoietic cells in human
      fetal liver and fetal and adult bone marrow. In the present report we show that
      HCA is also expressed by subsets of stromal cells in the primary hematopoietic
      sites that sequentially develop in the human embryo and fetus, ie, the paraaortic
      mesoderm, liver, thymus, and bone marrow. Adult bone marrow stromal cells
      established in vitro, including those derived from Stro-1(+) progenitors and
      cells from immortalized cell lines, express HCA. In contrast, no HCA expression
      could be detected in peripheral lymphoid tissues, fetal spleen, and lymph nodes.
      HCA membrane molecules purified from marrow stromal cells interact with intact
      marrow stromal cells, CD34(+) CD38(-) hematopoietic precursors, and CD3(+) CD6(+)
      peripheral blood lymphocytes. Finally, low but significant levels of CD6 are here
      for the first time detected at the surface of CD34(+) rho123(med/lo) progenitors
      in the bone marrow and in mobilized blood from healthy individuals. Altogether,
      these results indicate that the HCA/ALCAM surface molecule is involved in
      homophilic or heterophilic (with CD6) adhesive interactions between early
      hematopoietic progenitors and associated stromal cells in primary blood-forming
      organs.

PMID- 9920832
TI  - Notch1-induced delay of human hematopoietic progenitor cell differentiation is
      associated with altered cell cycle kinetics.
AB  - Hematopoiesis is a balance between proliferation and differentiation that may be
      modulated by environmental signals. Notch receptors and their ligands are highly
      conserved during evolution and have been shown to regulate cell fate decisions in
      multiple developmental systems. To assess whether Notch1 signaling may regulate
      human hematopoiesis to maintain cells in an immature state, we transduced a
      vesicular stomatitis virus G-protein (VSV-G) pseudo-typed bicistronic murine stem
      cell virus (MSCV)-based retroviral vector expressing a constitutively active form
      of Notch1 (ICN) and green fluorescence protein into the differentiation competent
      HL-60 cell line and primary cord blood-derived CD34(+) cells. In addition, we
      observed endogenous Notch1 expression on the surface of both HL-60 cells and
      primary CD34(+) cells, and therefore exposed cells to Notch ligand Jagged2,
      expressed on NIH3T3 cells. Both ligand-independent and ligand-dependent
      activation of Notch resulted in delayed acquisition of differentiation markers by
      HL-60 cells and cord blood CD34(+) cells. In addition, primary CD34(+) cells
      retained their ability to form immature colonies, colony-forming unit-mix (CFU
      mix), whereas control cells lost this capacity. Activation of Notch1 correlated
      with a decrease in the fraction of HL-60 cells that were in G0/G1 phase before
      acquisition of a mature cell phenotype. This enhanced progression through G1 was
      noted despite preservation of the proliferative rate of the cells and the overall
      length of the cell cycle. These findings show that Notch1 activation delays human
      hematopoietic differentiation and suggest a link of Notch differentiation effects
      with altered cell cycle kinetics.

PMID- 9920833
TI  - A secreted proform of neutrophil proteinase 3 regulates the proliferation of
      granulopoietic progenitor cells.
AB  - Myeloid leukemia cells, the human promyelocytic cell line HL-60, and a
      subpopulation of normal marrow cells produce a leukemia-associated inhibitor
      (LAI) that reversibly downmodulates DNA synthesis of normal granulopoietic
      progenitor cells colony-forming unit granulocyte-macrophage (CFU-GM). We isolated
      an active 125-kD component of LAI from HL-60 conditioned medium (CM), subjected
      it to cyanogen bromide cleavage and show by amino acid sequencing of the
      resulting peptides that it consists of a complex of the serine proteinase
      inhibitor alpha1-antitrypsin and a 31-kD fragment that retained the S-phase
      inhibitory activity, but resisted sequencing. This finding suggested that the 31
      kD fragment originated from one of the neutrophil serine proteases (ie, elastase,
      proteinase 3, or cathepsin G) produced by normal promyelocytes, as well as HL-60
      cells, for storage in primary granules and partly secreted during synthesis as
      enzymatically inactive proforms. Immunoblot analysis showed that the 125-kD
      complex contained proteinase 3 (PR3), and immunoprecipitation of PR3 from HL-60
      CM abrogated the S-phase inhibitory activity, whereas immunoprecipitation of
      cathepsin G or elastase did not. Immunoprecipitation of PR3 from CM of a
      subpopulation of normal marrow cells also abrogated the S-phase inhibitory
      effect. Furthermore, CM from rat RBL and murine 32D cell lines transfected with
      human PR3 both reduced the fraction of CFU-GM in S-phase with 30% to 80% at 1 to
      35 ng/mL PR3, whereas CM of the same cells transfected with cathepsin G or
      elastase did not. Also, an enzymatically silent mutant of PR3 exerted full
      activity, showing that the S-phase modulatory effect is not dependent on
      proteolytic activity. Amino acid sequencing of biosynthetically radiolabeled PR3
      showed that PR3 from transfected cells is secreted after synthesis as proforms
      retaining amino terminal propeptides. In contrast, mature PR3 extracted from
      mature neutrophils has only minor activity. The inhibitory effect of secreted PR3
      is reversible and abrogated by granulocyte (G)- or granulocyte-macrophage colony
      stimulating factor (GM-CSF). Experiments with highly purified CD34(+) bone marrow
      cells suggested that PR3 acts directly on the granulopoietic progenitor cells.
      These observations suggest a role for PR3 in regulation of granulopoiesis, and
      possibly in suppression of normal granulopoiesis in leukemia.

PMID- 9920834
TI  - The MKK6/p38 stress kinase cascade is critical for tumor necrosis factor-alpha
      induced expression of monocyte-chemoattractant protein-1 in endothelial cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C subfamily of
      chemokines, is important for the local recruitment of leukocytes to sites of
      inflammatory challenge. Here, we investigated endothelial signaling pathways
      involving members of the mitogen-activated protein (MAP) kinase superfamily and
      studied their role for MCP-1 expression in endothelium. We show that tumor
      necrosis factor-alpha (TNF-alpha), a potent inflammatory activator of
      endothelium, leads to activation of MAP kinases ERK, p38, and JNK in human
      umbilical vein endothelial cells (HUVEC). Contribution of MAP kinase pathways to
      TNF-alpha-induced synthesis of endothelial MCP-1 was then studied by
      pharmacologic inhibition and transient expression of dominant negative or
      constitutively active kinase mutants using flow cytometry, Northern blot, and
      luciferase reporter gene assays. Inhibition of Raf/MEK/ERK or SEK/JNK pathways
      had no significant effect on MCP-1 levels, whereas blocking the MKK6/p38 pathway
      by p38 inhibitors SB203580 or SB202190 or by a dominant negative mutant of MKK6,
      the upstream activator of p38, strongly inhibited TNF-alpha-induced expression of
      MCP-1. Consistent with that finding, expression of wild-type or constitutively
      active MKK6 significantly enhanced the effect of limiting TNF-alpha
      concentrations on MCP-1 synthesis. These data suggest a crucial role for the
      MKK6/p38 stress kinase cascade in TNF-alpha-mediated endothelial MCP-1
      expression.

PMID- 9920835
TI  - Molecular genetic analysis of a compound heterozygote for the glycoprotein (GP)
      IIb gene associated with Glanzmann's thrombasthenia: disruption of the 674-687
      disulfide bridge in GPIIb prevents surface exposure of GPIIb-IIIa complexes.
AB  - This work was aimed at elucidating the molecular genetic lesion(s) responsible
      for the thrombasthenic phenotype of a patient whose low platelet content of
      glycoprotein (GP) IIb-IIIa indicated that it was a case of type II Glanzmann's
      thrombasthenia (GT). The parents did not admit consanguinity and showed a reduced
      platelet content of GPIIb-IIIa. Polymerase chain reaction (PCR)-single-stranded
      conformational polymorphism analysis of genomic DNA showed no mutations in the
      patient's GPIIIa and two novel mutations in the GPIIb gene: one of them was a
      heterozygous splice junction mutation, a C-->A transversion, at position +2 of
      the exon 5-intron 5 boundary [IVS5(+2)C-->A] inherited from the father. The
      predicted effect of this mutation, insertion of intron 5 (76 bp) into the GPIIb
      mRNA, was confirmed by reverse transcription-PCR analysis of platelet mRNA. The
      almost complete absence of this mutated form of GPIIb-mRNA suggests that it is
      very unstable. Virtually all of the proband's GPIIb-mRNA was accounted for by the
      allele inherited from the mother showing a T2113-->C transition that changes
      Cys674-->Arg674 disrupting the 674-687 intramolecular disulfide bridge. The
      proband showed a platelet accumulation of proGPIIb and minute amounts of GPIIb
      and GPIIIa. Moreover, transfection and immunoprecipitation analysis demonstrated
      that [Arg674]GPIIb is capable of forming a heterodimer complex with GPIIIa, but
      the rate of subunit maturation and the surface exposure of GPIIb-IIIa are
      strongly reduced. Thus, the intramolecular 674-687 disulfide bridge in GPIIb is
      essential for the normal processing of GPIIb-IIIa complexes. The additive effect
      of these two GPIIb mutations provides the molecular basis for the thrombasthenic
      phenotype of the proband.

PMID- 9920836
TI  - Platelet/polymorphonuclear leukocyte interaction: P-selectin triggers protein
      tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a
      signaling molecule.
AB  - Polymorphonuclear leukocyte (PMN) adhesion to activated platelets is important
      for the recruitment of PMN at sites of vascular damage and thrombus formation. We
      have recently shown that binding of activated platelets to PMN in mixed cell
      suspensions under shear involves P-selectin and the activated beta2-integrin
      CD11b/CD18. Integrin activation required signaling mechanisms that were sensitive
      to tyrosine kinase inhibitors.1 Here we show that mixing activated,
      paraformaldehyde (PFA)-fixed platelets with PMNs under shear conditions leads to
      rapid and fully reversible tyrosine phosphorylation of a prominent protein of 110
      kD (P approximately 110). Phosphorylation was both Ca2+ and Mg2+ dependent and
      was blocked by antibodies against P-selectin or CD11b/CD18, suggesting that both
      adhesion molecules need to engage with their respective ligands to trigger
      phosphorylation of P approximately 110. The inhibition of P approximately 110
      phosphorylation by tyrosine kinase inhibitors correlates with the inhibition of
      platelet/PMN aggregation. Similar effects were observed when platelets were
      substituted by P-selectin-transfected Chinese hamster ovary (CHO-P) cells or when
      PMN were stimulated with P-selectin-IgG fusion protein. CHO-P/PMN mixed-cell
      aggregation and P-selectin-IgG-triggered PMN/PMN aggregation as well as P
      approximately 110 phosphorylation were all blocked by antibodies against P
      selectin or CD18. In each case PMN adhesion was sensitive to the tyrosine kinase
      inhibitor genistein. The antibody PL-1 against P-selectin glycoprotein ligand-1
      (PSGL-1) blocked platelet/PMN aggregation, indicating that PSGL-1 was the major
      tethering ligand for P-selectin in this experimental system. Moreover, engagement
      of PSGL-1 with a nonadhesion blocking antibody triggered beta2-integrin-dependent
      genistein-sensitive aggregation as well as tyrosine phosphorylation in PMN. This
      study shows that binding of P-selectin to PSGL-1 triggers tyrosine kinase
      dependent mechanisms that lead to CD11b/CD18 activation in PMN. The availability
      of the beta2-integrin to engage with its ligands on the neighboring cells is
      necessary for the tyrosine phosphorylation of P approximately 110.

PMID- 9920838
TI  - Genotype/phenotype correlations for coagulation factor XIII: specific normal
      polymorphisms are associated with high or low factor XIII specific activity.
AB  - Factor XIII is a transglutaminase essential for normal hemostasis. We have
      studied the plasma FXIII levels and FXIII activity in 71 individuals and found
      these to be normally distributed. FXIII specific activity is also normally
      distributed. However, we show that FXIII activity is not directly dependent on
      FXIII levels, and individuals with low FXIII levels may have high FXIII activity
      and vice versa. We have determined the FXIIIA genotype in these individuals to
      assess whether the variation observed in FXIII specific activity is dependent on
      specific polymorphisms in the FXIIIA gene. Our data show that the Leu34 and
      Leu564 variants give rise to increased FXIII specific activity, while the Phe204
      variant results in lower FXIII specific activity. We also report preliminary
      evidence that the Phe204 polymorphism may be associated with recurrent
      miscarriage. Overall, we have identified 23 unique FXIIIA genotypes. Certain
      specific FXIIIA genotypes consistently give rise to high, low, or median FXIII
      specific activity levels, while others appear to have little or no consistent
      influence on the FXIII phenotype. These genotype to phenotype relationships are
      discussed in light of the growing interest in the role of FXIII in clinical
      problems involving an increased thrombotic tendency.

PMID- 9920837
TI  - Activation of peripheral blood T cells by interaction and migration through
      endothelium: role of lymphocyte function antigen-1/intercellular adhesion
      molecule-1 and interleukin-15.
AB  - Cell adhesion molecules have a key role in the migration of T cells to
      inflammatory foci. However, the effect of the endothelial-lymphocyte interaction
      on the activation of the latter cells remains unresolved. We have studied the
      effect of resting and stimulated endothelial cells (ECs) on the activation of
      peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25
      activation antigens. The incubation of PBTLs with tumor necrosis factor-alpha
      activated EC monolayers, either alive or fixed, induced the expression of CD69
      but not CD25, preferentially in the CD8(+) CD45RO+ cell subset. Furthermore, it
      induced the production of cytokines such as IFN-gamma, but not that of
      interleukin-2 (IL-2) and IL-4. EC treated with other stimuli such as IL-1beta,
      IFN-gamma, or lipopolysaccharide also showed the same proactivatory effect on T
      cells. Lymphocyte activation was almost completely inhibited by blocking anti
      CD18 and anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal
      antibodies (MoAbs), but only slightly affected by MoAbs against CD49d, vascular
      cell adhesion molecule-1, and anti-IL-15. In addition, the interaction of PBTL
      with immobilized ICAM-1 induced CD69 expression in the same memory T-cell subset.
      IL-15 induced T-cell activation with expression of CD69 and CD25, and production
      of IFN-gamma, and its effect was additive with that triggered by cell adhesion to
      either EC or immobilized ICAM-1. The transmigration of PBTLs through either
      confluent EC monolayers or ICAM-1-coated membranes also induced efficiently the
      expression of CD69. When IL-15 was used as chemoattractant in these assays, a
      further enhancement in CD69 expression was observed in migrated cells. Together
      these results indicate that stimulated endothelium may have an important role in
      T-cell activation, through the lymphocyte function antigen-1/ICAM-1 pathway, and
      that IL-15 efficiently cooperates in this phenomenon. These observations could
      account for the abundance of CD69(+) cells in the lymphocytic infiltrates of
      several chronic inflammatory diseases.

PMID- 9920839
TI  - Association of a common polymorphism in the factor XIII gene with venous
      thrombosis.
AB  - We have shown an association between a common mutation in the factor XIII a
      subunit gene, coding for an amino acid change, 3 amino acids from the thrombin
      activation site (factor XIII Val34Leu) that may protect against myocardial
      infarction and predisposes to intracranial hemorrhage. To investigate the
      possible role of factor XIII Val34Leu in the pathogenesis of venous
      thromboembolism (VTE) and potential interactions with factor V Leiden (FV:Q506)
      and prothrombin G --> A 20210, we studied 221 patients with a history of VTE and
      254 healthy controls. Patients with VTE showed an increased frequency of the
      FXIII Val/Val genotype (63% v 49%) and a lower frequency of the Val/Leu genotype
      (31% v 42%) than controls (P =. 007). FV:Q506 heterozygotes were more frequent in
      VTE patients (11%) than controls (5%; P =.04). The prothrombin G --> A 20210
      mutation was present in only 3 patients and no controls (P =.10). In a logistic
      regression model for a history of VTE, the odds ratio (95% confidence interval)
      for FXIII Val/Leu or Leu/Leu genotype was 0.63 (0.38 to 0.82) and for possession
      of FV:Q506 2.40 (1.17 to 4.90). There was no evidence for an interaction between
      factor XIII Val34Leu genotype and FV:Q506, prothrombin G --> A 20210, sex, or
      age. It is concluded that possession of the Leu allele at factor XIII Val34Leu is
      protective against deep venous thrombosis.

PMID- 9920840
TI  - Autoimmune antibody in a hemorrhagic patient interacts with thrombin-activated
      factor XIII in a unique manner.
AB  - Without a prior history of hemorrhagic disease, a 62-year-old man suffered
      recurrent episodes of bleeding. Solubility of the patient's clot in 5 mol/L urea
      indicated a problem with fibrin stabilization. The transamidase activity
      potential of factor XIII, measured by the incorporation of radioactive putrescine
      into N,N-dimethylcasein as test substrate, was 62% of control, close to the
      normal range of values. Examination of the patient's clot from recalcified plasma
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that
      essentially none of the alpha chains and only about two thirds of the gamma
      chains of fibrin became cross-linked under conditions where both were fully cross
      linked in the controls. An antibody to factor XIII was isolated which, although
      recognizing the recombinant rA2 subunits, as well as the virgin A2B2 plasma
      ensemble, showed a 100-fold greater affinity for the thrombin-activated rA2' and
      A2'B2 forms of the zymogen, suggesting that the latter would be its main target
      during coagulation. Furthermore, the patient's IgG has an ability, never seen
      before, for inducing an enzymatically active configuration in the thrombin
      activated zymogen in the absence of Ca2+.

PMID- 9920841
TI  - A mutation in the alpha subunit of the platelet integrin alphaIIbbeta3 identifies
      a novel region important for ligand binding.
AB  - An unbiased genetic approach was used to identify a specific amino acid residue
      in the alphaIIb subunit important for the ligand binding function of the integrin
      alphaIIbbeta. Chemically mutagenized cells were selected by flow cytometry based
      on their inability to bind the ligand mimetic antibody PAC1 and a cell line
      containing a single amino acid substitution in alphaIIb at position 224 (D-->V)
      was identified. Although well expressed on the surface of transfected cells,
      alphaIIbD224Vbeta3 as well as alphaIIbD224Abeta3 did not bind alphaIIbbeta3
      specific ligands or a RGD peptide, a ligand shared in common with alphavbeta3.
      Insertion of exon 5 of alphaIIb, residues G193-W235, into the backbone of the
      alphav subunit did not enable the chimeric receptor to bind alphaIIbbeta3
      specific ligands. However, the chimeric receptor was still capable of binding to
      a RGD affinity matrix. alphaIIbD224 is not well conserved among other integrin
      alpha subunits and is located in a region of significant variability. In
      addition, amino acid D224 lies within a predicted loop of the recently proposed
      beta-propeller model for integrin alpha subunits and is adjacent to a loop
      containing amino acid residues previously implicated in receptor function. These
      data support a role for this region in ligand binding function of the
      alphaIIbbeta3 receptor.

PMID- 9920843
TI  - Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term
      nonprogressor status in human immunodeficiency virus-1-infected individuals.
AB  - Human immunodeficiency virus (HIV)-1-infected long-term nonprogressors (LT-NP)
      represent less than 5% of HIV-1-infected patients. In this work, we tried to
      understand whether combined genotypes of CCR5-triangle up32, CCR2-64I, SDF1-3'A
      and HLA alleles can predict the LT-NP status. Among the chemokine receptor
      genotypes, only the frequency of the CCR5-triangle up32 allele was significantly
      higher in LT-NP compared with the group of standard progressors. The predominant
      HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA-B27, HLA-DR6, and HLA
      DR7. A combination of both HLA and chemokine receptor genotypes integrated in a
      multivariate logistic regression model showed that if a subject is heterozygous
      for CCR5-triangle up32 and homozygous for SDF1 wild type, his odds of being LT-NP
      are increased by 16-fold, by 47-fold when a HLA-B27 allele is present with HLA
      DR6 absent, and by 47-fold also if at least three of the following alleles are
      present: HLA-A3, HLA-B14, HLA-B17, HLA-DR7. This model allowed a correct
      classification of 70% of LT-NPs and 81% of progressors, suggesting that the
      host's genetic background plays an important role in the evolution of HIV-1. The
      chemokine receptor and chemokine genes along with the HLA genotype can serve as
      predictors of HIV-1 outcome for classification of HIV-1-infected subjects as LT
      NPs or progressors.

PMID- 9920842
TI  - Fas-independent and nonapoptotic cytotoxicity mediated by a human CD4(+) T-cell
      clone directed against an acute myelogenous leukemia-associated DEK-CAN fusion
      peptide.
AB  - The mechanism underlying the cytotoxicity mediated by a human CD4(+) cytotoxic T
      lymphocyte (CTL) clone directed against a peptide derived from the acute
      myelogenous leukemia-associated fusion protein, DEK-CAN, was investigated. A DEK
      CAN fusion peptide-specific CD4(+) Th0 CTL clone, designated HO-1, was
      established from the peripheral blood lymphocytes of a healthy individual. HO-1
      exerted direct but not "innocent bystander" cytotoxicity within 2 hours. The
      cytotoxicity mediated by HO-1 was completely Ca2+-dependent. Because HO-1 lysed
      peptide-loaded Fas-deficient target cells derived from a patient with a
      homozygous Fas gene mutation, its cytotoxicity appeared to be mediated by a Fas
      independent pathway. In addition, its cytotoxicity was only partially inhibited
      by treatment with concanamycin A and strontium ions, which are inhibitors of the
      perforin-based cytotoxic pathway. Although membrane-bound type of tumor necrosis
      factor-alpha (TNF-alpha) was expressed on HO-1, an anti-TNF-alpha antibody had no
      effect on HO-1-mediated cytotoxicity. HO-1 expressed mRNA for apoptosis-inducing
      mediators, including perforin, granzyme B, Fas ligand, TNF-alpha, and
      lymphotoxin; however, no DNA fragmentation was detected in target cells incubated
      with HO-1 by 5-[125I]Iodo-2'-deoxyuridine release assay and agarose gel
      electrophoresis of DNA. Although it has been suggested that the Fas/Fas ligand
      system is the main pathway by which CD4(+) CTL-mediated cytotoxicity is exerted
      in murine systems, HO-1 produced peptide-specific and HLA-restricted cytotoxicity
      via a Fas-independent and nonapoptotic pathway. The present study thus describes
      a novel mechanism of cytotoxicity mediated by CD4(+) CTL.

PMID- 9920844
TI  - Immunoglobulin M-enriched human intravenous immunoglobulin prevents complement
      activation in vitro and in vivo in a rat model of acute inflammation.
AB  - An important antiinflammatory mechanism of intravenous immunoglobulin
      preparations (IVIG) is their ability to block complement activation. The purpose
      of this study was to compare the complement-inhibitory activity of four IVIG
      preparations differing in isotype composition. The preparations were: (1) IVIgG
      (48 g/L IgG, 2 g/L IgA; Intraglobin F); (2) Pentaglobin (38 g/L IgG, 6 g/L IgM, 6
      g/L IgA); (3) IVIgM (35 g/L IgM, 12 g/L IgA, 3 g/L IgG); and (4) IVIgA (41 g/L
      IgA, 9 g/L IgG), all from Biotest Pharma GmbH, Dreieich, Germany. Their
      complement inhibitory activity was assessed in vitro by measurement of the
      blocking of C1q-, C4-, and C3 deposition on solid-phase aggregated rabbit IgG by
      enzyme-linked immunosorbent assay (ELISA). Complement inhibition in this ELISA
      was best for IVIgM, followed by Pentaglobin and IVIgG; IVIgA did not exhibit an
      inhibitory effect. Control experiments with excess concentrations of C1q as well
      as with C1q-depleted serum showed that the inhibitory effects of IVIG were not
      caused by complement activation and thus, consumption, but that C4 and C3 were
      scavenged by IgM and to a lesser extent by IgG. These results were confirmed in
      vivo in the rat anti-Thy 1 nephritis model, in which a single dose of 500 mg/kg
      of IVIgM prevented C3-, C6-, and C5b-9 deposition in the rat glomeruli, whereas
      the effect of IVIgG was much less pronounced. Reduction of complement deposition
      was paralleled by a diminished albuminuria, which was completely absent in the
      IVIgM-treated rats. IVIgM and to a lesser extent IVIgG also prevented rat C3
      deposition on cultured rat glomerular mesangial cells in vitro, but did not
      influence anti-Thy 1 binding. Neither IVIgM nor Pentaglobin nor IVIgG negatively
      affected in vitro phagocytosis of Escherichia coli (E coli) by human
      granulocytes. In conclusion, we have shown that IgM enrichment of IVIG
      preparations enhances their effect to prevent the inflammatory effects of
      complement activation.

PMID- 9920845
TI  - Shaping the repertoire of cytotoxic T-lymphocyte responses: explanation for the
      immunodominance effect whereby cytotoxic T lymphocytes specific for
      immunodominant antigens prevent recognition of nondominant antigens.
AB  - The immunodominance effect, whereby the presence of immunodominant epitopes
      prevents recognition of nondominant determinants presented on the same antigen
      presenting cell (APC) considerably restricts the repertoire of cytotoxic T
      lymphocyte (CTL) responses. To elucidate the molecular basis of the
      immunodominance effect, we compared the interactions of a dominant (B6(dom1)) and
      a nondominant epitope (H-Y) with their restricting class I molecule (H2-Db), and
      their ability to trigger cognate CTLs. We found that B6(dom1)/Db complexes
      behaved as optimal T-cell receptor (TCR) ligands and triggered a more rapid in
      vivo expansion of cognate CTLs than H-Y/Db complexes. The superiority of the
      dominant epitope was explained by its high cell surface density (1,012
      copies/cell for B6(dom1) v 10 copies/cell for H-Y) and its optimal affinity for
      cognate TCRs. Based on these results, we conclude that dominant class I
      associated epitopes are those that have optimal ability to trigger TCR signals in
      CTLs. We propose that the rapid expansion of CTLs specific for dominant antigens
      should enable them to compete more successfully than other CTLs for occupancy of
      the APC surface.

PMID- 9920846
TI  - The 5' flanking region of the human granzyme H gene directs expression to
      T/natural killer cell progenitors and lymphokine-activated killer cells in
      transgenic mice.
AB  - Human granzyme H is a neutral serine protease that is expressed predominantly in
      the lymphokine-activated killer (LAK)/natural killer (NK) compartment of the
      immune system. The gene that encodes this granzyme is located between the
      granzyme B and cathepsin G genes on human chromosome 14q11.2. Although the murine
      orthologue of human granzyme H has not yet been identified, murine granzymes C,
      D, E, F, and G also lie between the murine granzyme B and cathepsin G genes on
      murine chromosome 14; murine granzymes C, D, and F are also highly expressed in
      LAK cells, but minimally in cytotoxic T lymphocytes (CTL). We therefore tested
      whether the 5' flanking region of human granzyme H contains the cis-acting DNA
      sequences necessary to target a reporter gene to the LAK/NK compartment of
      transgenic mice. A 1.2-kb fragment of 5' flanking human granzyme H sequence was
      linked to an SV40 large T-antigen (TAg) reporter gene and used to create six
      transgenic founder lines. SV40 TAg was specifically expressed in the LAK cells of
      these mice, but not in resting T or NK cells, in CTL, or in any other tissues.
      Most mice eventually developed a fatal illness characterized by massive
      hepatosplenomegaly and disseminated organ infiltration by large malignant
      lymphocytes. Cell lines derived from splenic tumors were TAg+ and NK1.1(+) large
      granular lymphocytes and displayed variable expression of CD3, CD8, and CD16.
      Although these cell lines contained perforin and expressed granzymes A, B, C, D,
      and F, they did not exhibit direct cytotoxicity. Collectively, these results
      suggest that the 5' flanking sequences of the human granzyme H gene target
      expression to an NK/T progenitor compartment and to activated NK (LAK) cells.
      Mice and humans may therefore share a regulatory "program" for the transcription
      of NK/LAK specific granzyme genes.

PMID- 9920848
TI  - Latent infection and reactivation of human herpesvirus 6 in two novel myeloid
      cell lines.
AB  - It has been reported that reactivation of human herpesvirus-6 (HHV-6) causes a
      failure of hematopoiesis. To clarify the mechanisms of bone marrow suppression
      induced by HHV-6 infection, it is necessary to establish an in vitro model of HHV
      6 infection in hematopoietic progenitor cells. We have established two novel
      Philadelphia chromosome-positive myeloid cell lines, SAS413 and SAS527, which
      possess different hematologic characteristics and show distinct susceptibility to
      infection by HHV-6, from a patient with blast crisis of chronic myelogenous
      leukemia (CML). HHV-6 subgroup A (HHV-6A) showed marked replication in SAS413,
      forming syncytia and inducing cell lysis in short-term culture. On the other
      hand, HHV-6A-inoculated SAS527 continued to proliferate without cell lysis and
      only a few cells showed HHV-6 antigen expression. In contrast to HHV-6A
      infection, inoculation with HHV-6 subgroup B (HHV-6B) did not induce any
      cytopathic effect (CPE) or viral antigen expression in either of the cell lines.
      Although HHV-6B replication was undetectable, the presence of the HHV-6 genome in
      both cell lines was shown by polymerase chain reaction (PCR) during culture for
      more than 10 months, suggesting that HHV-6B latently infected SAS413 and SAS527.
      Phorbol ester treatment of SAS527 latently infected with HHV-6B resulted in
      reactivation of HHV-6, as shown by the appearance of a CPE, positive reactivity
      for the HHV-6 antigen, and isolation of infectious HHV-6. These novel cell lines
      should be useful for studying the mechanisms of HHV-6-induced hematopoietic
      failure and HHV-6 latency and reactivation, as well as differentiation, of the
      myeloid cell lineage.

PMID- 9920847
TI  - Upregulated expression of fibronectin receptors underlines the adhesive
      capability of thymocytes to thymic epithelial cells during the early stages of
      differentiation: lessons from sublethally irradiated mice.
AB  - A 250-cGy whole-body gamma-radiation dose was used to induce thymus regression in
      mice, and to study the expression and function of extracellular matrix (ECM)
      receptors in distinct thymocyte subsets emerging during repopulation of the
      organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P
      Ir), when a remarkable increase in the absolute counts of CD3(-)CD25(hi)CD44(+)
      and CD3(-)CD25(in/hi)CD44(-) cells occurred. Enhanced expression of L-selectin,
      alpha4, and alpha5 integrin chains (L-selhi alpha4(hi) alpha5(hi)) was also
      exhibited by these cells. This pattern of expression was maintained until the
      CD4(+)CD8(+) (DP) young stage was achieved. Afterward, there was a general
      downregulation of these ECM receptors in DP as well as in CD4(+) or CD8(+) single
      positive (SP) thymocytes (L-selin alpha4(in) alpha5(in)). In some recently
      generated SP cells, alpha4 expression was downregulated before the alpha5 chain,
      and L-selectin was upregulated in half of more mature cells. The expression of
      the alpha6 integrin chain was downregulated only in maturing CD4(+) cells.
      Importantly, the increased expression of L-selectin and alpha4 and alpha5 chains
      in thymocytes was strongly correlated with their adhesiveness to thymic
      epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or
      peptides showed the following: (1) that the LDV rather than the REDV cell
      attachment motif in the IIIC segment of fibronectin is targeted by the alpha4
      integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD
      fragment of fibronectin, a target for alpha5 integrin, has a secondary role in
      this adhesion; and (3) that the YIGSR cell attachment motif of the beta1 chain of
      laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte
      adherence. In conclusion, our results show that an upregulated set of receptors
      endows CD25(+) precursors and cells up to the young DP stage with a high
      capability of interacting with thymic ECM components.

PMID- 9920849
TI  - Human immunodeficiency virus type 1 Nef protein sensitizes CD4(+) T lymphoid
      cells to apoptosis via functional upregulation of the CD95/CD95 ligand pathway.
AB  - Many viruses have evolved genes encoding proteins that regulate cell death by
      apoptosis. The human immunodeficiency virus type 1 (HIV-1) Nef protein alters T
      cell development and signaling and is required for optimal viral replication and
      pathogenicity in vivo. To analyze the interference of Nef with cell survival, we
      used both regulated and constitutively expressed nef alleles in stably
      transfected T-cell lines. Nef-expressing cells were sensitized to cell death by
      apoptosis, which was specifically exacerbated by an anti-CD95 IgM monoclonal
      antibody (MoAb). Flow cytometric analysis showed that the surface expression of
      both CD95 and CD95 ligand (CD95L) was upregulated by endogenous Nef expression.
      Nef-mediated apoptosis was almost completely suppressed by the addition in
      culture of an anti-CD95 Fab' IgG MoAb, which specifically blocks CD95/CD95L
      interactions. Lastly, mutation of a proline motif in the core region of the nef
      gene, which disrupts its ability to interact with cellular kinases and reduces
      HIV-1 replication in vitro, completely abrogated the Nef-mediated induction of
      apoptosis as well as its ability to upregulate surface CD95 and CD95L. These
      findings may provide molecular insight into the role of endogenous Nef in the T
      cell depletion observed in vivo, particularly HIV-specific cytotoxic CD8(+) T
      cells.

PMID- 9920850
TI  - Normal T-cell telomerase activity and upregulation in human immunodeficiency
      virus-1 infection.
AB  - In human immunodeficiency virus (HIV)-1 infection, decrease of telomere length is
      mainly found in CD8(+) T cells and not in CD4(+) T cells. Telomerase, a
      ribonucleoprotein enzyme that can synthesize telomeric sequence onto chromosomal
      ends, can compensate for telomere loss. Here, we investigated if telomerase
      activity could explain differential telomere loss of CD4(+) and CD8(+) T cells in
      HIV-1 infection. Telomerase activity was higher in CD8(+) than in CD4(+) T cells
      from HIV-infected patients, but still in the same range as in healthy controls,
      and upregulation after stimulation was comparable to normal. Telomerase activity
      in lymph node CD4(+) and CD8(+) T cells from HIV-infected patients was in the
      same range as that in CD4(+) and CD8(+) T cells from peripheral blood (PB) and
      was normal in unseparated bone marrow cells. Thus, our study did not provide
      evidence for compartmentalized elongation of telomeres in HIV infection. In
      patients treated with reverse transcriptase inhibitors, telomerase activity was
      inhibited, but this did not lead to accelerated loss of telomere length in vivo.
      Thus, differential telomere loss in CD4(+) and CD8(+) T cells in HIV-1 infection
      cannot be explained by telomerase activity.

PMID- 9920851
TI  - Direct alloreactivity by human cytotoxic T lymphocytes can Be inhibited by
      altered peptide ligand antagonism.
AB  - Alloreactive T lymphocytes that respond directly to foreign major
      histocompatibility complex (MHC) molecules and bound peptide are known to be
      central mediators of graft-versus-host disease (GVHD) and allograft rejection. We
      have recently identified a peptide from the human protein, cytochrome P450
      (isotypes IIC9, 10, or 18), that is recognized in association with human
      leukocyte antigen (HLA) B*3501 by alloreactive cytotoxic T lymphocytes (CTLs).
      These CTLs with this specificity were isolated from several unrelated individuals
      and were found to express a common T-cell receptor (TCR). Synthetic analogs of
      the cytochrome P450 peptide were generated by introducing single amino acid
      substitutions at putative TCR contact positions. Four altered peptide ligands
      were powerful competitive antagonists of these CTL clones, reducing lysis levels
      of target cells expressing the alloantigen HLA B*3501 by over 80%. This first
      demonstration that it is possible to suppress CTL alloreactivity with structural
      variants of allodeterminants raises the prospect that such TCR antagonists could
      be exploited within the clinical arena to specifically modulate GVHD and
      allograft rejection.

PMID- 9920852
TI  - Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia
      with the t(12;13)(p13;q12).
AB  - The t(12;13)(p13;q12) is a rare, recurrent translocation reported in a range of
      hematological malignancies. We have analyzed the molecular basis of this lesion
      in three patients with acute myeloid leukemia (AML), two of whom were known to
      have chromosome 12 breakpoints within the ETV6 gene. Fluorescence in situ
      hybridization (FISH) with ETV6 cosmids indicated that this gene was also
      disrupted in the third patient, while the normal ETV6 allele was retained. 3'
      rapid amplification of cDNA ends (RACE) polymerase chain reaction (PCR) from bone
      marrow mRNA of this individual identified a novel sequence fused to ETV6 that was
      homologous to a region just upstream of the mouse CDX2 homeobox gene, the human
      homologue of which has previously been mapped to chromosome 13q12. PCR primers
      designed to amplify an ETV6-CDX2 fusion identified two major transcripts from
      this patient. First, a direct in-frame fusion between exon 2 of ETV6 and exon 2
      of CDX2, and second, a transcript that had an additional sequence of unknown
      origin spliced between these same exons. Surprisingly, apparently normal CDX2
      transcripts, usually expressed only in intestinal epithelium, were also
      detectable in cDNA from this patient. Neither normal nor fusion CDX2 mRNA was
      detectable in the two other patients with a t(12;13), indicating that this
      translocation is heterogeneous at the molecular level. Reverse transcription-PCR
      analysis showed that CDX2 mRNA, but not ETV6-CDX2 mRNA, was strongly expressed in
      1 of 10 patients with chronic myeloid leukemia in transformation, suggesting that
      deregulation of this gene may be more widespread in leukemia. CDX2 is known to
      regulate class I homeobox genes and its expression in hematopoietic cells may
      critically alter the balance between differentiation and proliferation.

PMID- 9920853
TI  - Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and
      cytogenetic characteristics.
AB  - We report on a series of 26 patients diagnosed with primary (de novo) plasma cell
      (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of
      the disease together with the immunophenotype, DNA cell content, proliferative
      index, and numeric chromosomal aberrations of the neoplastic PC, and compared
      them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex
      ratio, and bone lesion extension were similar, but PCL cases displayed a higher
      prevalence of clinical stage III, extramedullary involvement, and Bence Jones
      cases, with fewer IgA cases than for MM patients. In addition, according to
      several prognostic indicators (beta2-microglobulin serum level, proportion of S
      phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and
      renal function), the incidence of adverse prognostic factors was significantly
      higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138,
      CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression
      of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid
      and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With
      the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases
      displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in
      women (25%), but they lacked several numeric aberrations usually found in MM such
      as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy
      than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse
      response was observed in cases treated with melphalan and prednisone (MP) versus
      polychemotherapy. Overall survival was significantly worse in PCL versus MM
      patients (8 v 36 months, P <.0001), but it was significantly better in PCL
      patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By
      contrast, MM patients did not show significant differences in overall survival
      according to the treatment used, MP or polychemotherapy. Ten variables seemed to
      predict survival in PCL patients, but only the beta2-microglobulin level and S
      phase PCs retained an independent value in multivariate analysis. In summary, our
      study illustrates that PCs from PCL display singular phenotypic, DNA cell
      content, and cytogenetic characteristics that lead to a different disease
      evolution versus MM.

PMID- 9920854
TI  - Antineoplastic urinary protein inhibits Kaposi's sarcoma and angiogenesis in
      vitro and in vivo.
AB  - Kaposi's sarcoma (KS) is the most common tumor in human immunodeficiency virus
      infection and acquired immune deficiency syndrome. Recent clinical trials with
      human chorionic gonadotropin (hCG) prepared from early pregnancy urine have shown
      encouraging results in the resolution of KS lesions. A urinary protein with
      antitumor activity, ANUP (antineoplastic urinary protein), a dimer of 32 kD, has
      previously been shown to inhibit the growth of various tumor cell lines in vivo.
      It was thus studied for its activity in KS cell lines in vitro and in vivo to
      determine whether it could be a source of the anti-KS activity observed in hCG
      preparations. ANUP is a strong growth inhibitor for KS cell lines, but has little
      or no effect on fibroblast, aortic smooth muscle, T- and B-lymphocyte, and
      monocyte cell lines. ANUP also inhibited the proliferation of endothelial cell
      lines, suggesting that the in vitro effects were endothelial cell lineage
      specific. However, ANUP antibodies did not block the inhibitory effect of certain
      commercial preparations of hCG, previously shown to be active in KS. Thus, the
      active protein in these commercial preparations of hCG may be distinct from ANUP.
      The antitumor activity of ANUP was further confirmed in a chicken allantoic
      membrane (CAM) assay in which vascular endothelial growth factor (VEGF) and beta
      fibroblast growth factor (bFGF)-induced angiogenesis was inhibited by ANUP in a
      dose-dependent manner. In vivo activity of ANUP was demonstrated in the murine
      model of KS, where ANUP inhibited tumor growth. ANUP is thus a potential
      candidate for development in the treatment of KS and other diseases in which
      angiogenesis plays an important role.

PMID- 9920855
TI  - The novel synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene
      carboxylic acid (CD437) causes apoptosis in acute promyelocytic leukemia cells
      through rapid activation of caspases.
AB  - The synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic
      acid (CD437), which was originally developed as an retinoic acid receptor (RAR)
      gamma agonist, induces rapid apoptosis in all-trans retinoic acid (ATRA)
      sensitive and ATRA-resistant clones of the NB4 cell line, a widely used
      experimental model of acute promyelocytic leukemia (APL). In addition, the
      compound is apoptogenic in primary cultures of freshly isolated APL blasts
      obtained from a newly diagnosed case and an ATRA-resistant relapsed patient. NB4
      cells in the S-phase of the cycle are most sensitive to CD437-triggered
      apoptosis. CD437-dependent apoptosis does not require de novo protein synthesis
      and activation of RAR-gamma or any of the other nuclear retinoic acid receptors.
      The process is preceded by rapid activation of a caspase-like enzymatic activity
      capable of cleaving the fluorogenic DEVD but not the fluorogenic YVAD
      tetrapeptide. Increased caspase activity correlates with caspase-3 and caspase-7
      activation. Inhibition of caspases by z-VAD suppresses the nuclear DNA
      degradation observed in NB4 cells treated with CD437, as well as the degradation
      of pro-caspase-3 and pro-caspase-7. CD437-dependent activation of caspases is
      preceded by release of cytochrome c from the mitochondria into the cytosol of
      treated cells. Leakage of cytochrome c lays upstream of caspase activation,
      because the phenomenon is left unaffected by pretreatment of NB4 cells with z
      VAD. Treatment of APL cells with CD437 is associated with a caspase-dependent
      degradation of promyelocytic leukemia-RAR-alpha, which can be completely
      inhibited by z-VAD.

PMID- 9920856
TI  - Long-term survival (10 years or more) in 30 patients with primary amyloidosis.
AB  - The median survival in primary systemic (AL) amyloidosis is less than 18 months.
      No published series of patients with AL amyloidosis have reported survival of
      more than 10 years. The records of all Mayo Clinic patients with a diagnosis of
      AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients
      with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis,
      and localized amyloidosis were excluded. During the 21 years of the study, 841
      patients with AL amyloidosis were seen. Of these, 29 were excluded because the
      diagnosis was made at autopsy, and 2 others were excluded because no follow-up
      data were available. Actuarial survival for the 810 patients was 51% at 1 year,
      16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or
      more after the histologic diagnosis of AL amyloidosis; all received alkylating
      agent therapy. In 14 patients, the monoclonal protein disappeared from the serum
      or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response.
      Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone
      marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less,
      and the presence of peripheral neuropathy were underrepresented in the 10-year
      survivors and are unfavorable prognostic features. Five percent of patients with
      AL amyloidosis survived for 10 years or more.

PMID- 9920857
TI  - Differential methotrexate resistance in childhood T- versus common/preB-acute
      lymphoblastic leukemia can be measured by an in situ thymidylate synthase
      inhibition assay, but not by the MTT assay.
AB  - Methotrexate (MTX) is not cytotoxic to patient-derived acute lymphoblastic
      leukemia (ALL) cells in total-cell-kill assays, such as the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, putatively due
      to the rescue effects of hypoxanthine and thymidine released from dying cells.
      This was mimicked by a diminished methotrexate (MTX) cytotoxicity for the cell
      lines HL60 and U937 in the presence of hypoxanthine, thymidine, or lysed ALL
      cells. However, enzymatic depletion or inhibition of nucleoside membrane
      transport did not result in MTX dose-dependent cytotoxicity in patient samples.
      Alternatively, a thymidylate synthase inhibition assay (TSIA), based on
      inhibition of the TS-catalyzed conversion of 3H-dUMP to dTMP and 3H2O, correlated
      with the MTT assay for antifolate sensitivity in four human leukemia cell lines
      with different modes of MTX resistance. For 86 ALL patient samples, TSI50 values
      after 21 hours exposure to MTX were not different between T- and c/preB-ALL (P
      =.46). After 3 hours incubation with MTX followed by an 18-hour drug-free period,
      T-ALL samples were 3.4-fold more resistant to MTX compared with c/preB-ALL
      samples (P =.001) reflecting the clinical differences in MTX sensitivity. TSI50
      values correlated with MTX accumulation (r = -.58, P <.001). In conclusion, the
      TSIA, but not the MTT assay, can measure dose-response curves for MTX in patient
      derived ALL cells and showed relative MTX resistance in T-ALL compared with
      c/preB-ALL.

PMID- 9920858
TI  - P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase
      independent, cell death.
AB  - A major problem with treating patients with cancer by traditional
      chemotherapeutic regimes is that their tumors often develop a multidrug resistant
      (MDR) phenotype and subsequently become insensitive to a range of different
      chemotoxic drugs. One cause of MDR is overexpression of the drug-effluxing
      protein, P-glycoprotein. It is now apparent that P-glycoprotein may also possess
      a more generic antiapoptotic function that protects P-glycoprotein-expressing
      cancer cells and normal cells from cell death. Herein we show that cells induced
      to express P-glycoprotein either by drug selection or by retroviral gene
      transduction with MDR1 cDNA are resistant to cell death induced by a wide range
      of death stimuli, such as FasL, tumor necrosis factor (TNF), and ultraviolet (UV)
      irradiation, that activate the caspase apoptotic cascade.However, P-glycoprotein
      expressing cells were not resistant to caspase-independent cell death mediated by
      pore-forming proteins and granzyme B.MDR P-glycoprotein-expressing cells were
      made sensitive to caspase-dependent apoptosis by the addition of anti-P
      glycoprotein antibodies or verapamil, a pharmacological inhibitor of P
      glycoprotein function. Clonogenic assays showed that P-glycoprotein confers long
      term resistance to caspase-dependent apoptotic stimuli but not to caspase
      independent cell death stimuli. This study has confirmed a potential novel
      physiological function for P-glycoprotein and it now remains to dissect the
      molecular mechanisms involved in the inhibition of capsase-dependent cell death
      by P-glycoprotein.

PMID- 9920859
TI  - Biological inactivation of 5-oxo-6,8,11,14-eicosatetraenoic acid by human
      platelets.
AB  - Neutrophil-derived 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a potent
      activator of neutrophils and eosinophils. In the present study we examined the
      biosynthesis and metabolism of this substance by platelets. Although platelets
      contain an abundant amount of 5-hydroxyeicosanoid dehydrogenase, the enzyme
      responsible for the formation of 5-oxo-ETE, they synthesize only very small
      amounts of this substance from exogenous 5-hydroxyeicosatetraenoic acid (5-HETE)
      unless endogenous NADPH is converted to NADP+ by addition of phenazine
      methosulfate. Similarly, relatively small amounts of 5-oxo-ETE were formed by
      A23187-stimulated mixtures of platelets and neutrophils, which instead formed
      substantial amounts of two 12-hydroxy metabolites of this substance, 5-oxo-12
      HETE and 8-trans-5-oxo-12-HETE, which were identified by comparison with
      authentic chemically synthesized compounds. These metabolites were also formed
      from 5-oxo-ETE by platelets stimulated with thrombin or A23187. In contrast,
      unstimulated platelets converted 5-oxo-ETE principally to 5-HETE. Neither 5-oxo
      12-HETE nor 8-trans-5-oxo-12-HETE had appreciable effects on neutrophil calcium
      levels or platelet aggregation at concentrations as high as 10 micromol/L, but
      both blocked 5-oxo-ETE-induced calcium mobilization in neutrophils with IC50
      values of 0.5 and 2.5 micromol/L, respectively. We conclude that platelets can
      biologically inactivate 5-oxo-ETE. Unstimulated platelets convert 5-oxo-ETE to 5
      HETE, with a 99% loss of biological potency, whereas stimulated platelets convert
      this substance to 12-hydroxy metabolites, which possess antagonist properties.

PMID- 9920860
TI  - Delayed engraftment of nonobese diabetic/severe combined immunodeficient mice
      transplanted with ex vivo-expanded human CD34(+) cord blood cells.
AB  - The ex vivo expansion of hematopoietic progenitors is a promising approach for
      accelerating the engraftment of recipients, particularly when cord blood (CB) is
      used as a source of hematopoietic graft. With the aim of defining the in vivo
      repopulating properties of ex vivo-expanded CB cells, purified CD34(+) cells were
      subjected to ex vivo expansion, and equivalent proportions of fresh and ex vivo
      expanded samples were transplanted into irradiated nonobese diabetic (NOD)/severe
      combined immunodeficient (SCID) mice. At periodic intervals after
      transplantation, femoral bone marrow (BM) samples were obtained from NOD/SCID
      recipients and the kinetics of engraftment evaluated individually. The
      transplantation of fresh CD34(+) cells generated a dose-dependent engraftment of
      recipients, which was evident in all of the posttransplantation times analyzed
      (15 to 120 days). When compared with fresh CB, samples stimulated for 6 days with
      interleukin-3 (IL-3)/IL-6/stem cell factor (SCF) contained increased numbers of
      hematopoietic progenitors (20-fold increase in colony-forming unit granulocyte
      macrophage [CFU-GM]). However, a significant impairment in the short-term
      repopulation of recipients was associated with the transplantation of the ex vivo
      expanded versus the fresh CB cells (CD45(+) repopulation in NOD/SCIDs BM: 3. 7%
      +/- 1.2% v 26.2% +/- 5.9%, respectively, at 20 days posttransplantation; P
      <.005). An impaired short-term engraftment was also observed in mice transplanted
      with CB cells incubated with IL-11/SCF/FLT-3 ligand (3.5% +/- 1.7% of CD45(+)
      cells in femoral BM at 20 days posttransplantation). In contrast to these data, a
      similar repopulation with the fresh and the ex vivo-expanded cells was observed
      at later stages posttransplantation. At 120 days, the repopulation of CD45(+) and
      CD45(+)/CD34(+) cells in the femoral BM of recipients ranged between 67.2% to
      81.1% and 8.6% to 12.6%, respectively, and no significant differences of
      engraftment between recipients transplanted with fresh and the ex vivo-expanded
      samples were found. The analysis of the engrafted CD45(+) cells showed that both
      the fresh and the in vitro-incubated samples were capable of lymphomyeloid
      reconstitution. Our results suggest that although the ex vivo expansion of CB
      cells preserves the long-term repopulating ability of the sample, an unexpected
      delay of engraftment is associated with the transplantation of these manipulated
      cells.

PMID- 9920861
TI  - GLUT4 gene regulation and manipulation.

PMID- 9920862
TI  - The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by
      mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation
      in nerve terminals.
AB  - Clathrin-mediated endocytosis was shown to be arrested in mitosis due to a block
      in the invagination of clathrin-coated pits. A Xenopus mitotic phosphoprotein,
      MP90, is very similar to an abundant mammalian nerve terminal protein, epsin,
      which binds the Eps15 homology (EH) domain of Eps15 and the alpha-adaptin subunit
      of the clathrin adaptor AP-2. We show here that both rat epsin and Eps15 are
      mitotic phosphoproteins and that their mitotic phosphorylation inhibits binding
      to the appendage domain of alpha-adaptin. Both epsin and Eps15, like other
      cytosolic components of the synaptic vesicle endocytic machinery, undergo
      constitutive phosphorylation and depolarization-dependent dephosphorylation in
      nerve terminals. Furthermore, their binding to AP-2 in brain extracts is enhanced
      by dephosphorylation. Epsin together with Eps15 was proposed to assist the
      clathrin coat in its dynamic rearrangements during the invagination/fission
      reactions. Their mitotic phosphorylation may be one of the mechanisms by which
      the invagination of clathrin-coated pits is blocked in mitosis and their
      stimulation-dependent dephosphorylation at synapses may contribute to the
      compensatory burst of endocytosis after a secretory stimulus.

PMID- 9920863
TI  - Translational repression by human 4E-BP1 in yeast specifically requires human
      eIF4E as target.
AB  - 4E-binding proteins (4E-BPs) are believed to have important regulatory functions
      in controlling the rate of translation initiation in mammalian cells. They do so
      by binding to the mRNA cap-binding protein, eIF4E, thereby inhibiting formation
      of the cap-binding complex, a process essential for cap-dependent translation
      initiation. We have reproduced the translation-repressive function of human 4E
      BP1 in yeast and find its activity to be dependent on substitution of human eIF4E
      for its yeast counterpart. Translation initiation and growth are inhibited when
      human 4E-BP1 is expressed in a strain with the human eIF4E substitution, but not
      in an unmodified strain. We have compared the relative affinities of human 4E-BP1
      for human and yeast eIF4E, both in vitro using an m7GTP cap-binding assay and in
      vivo using a yeast two-hybrid assay, and find that the affinity of human 4E-BP1
      for human eIF4E is markedly greater than for yeast eIF4E. Thus yeast eIF4E lacks
      structural features required for binding to human 4E-BP1. These results therefore
      demonstrate that the features of eIF4E required for binding to 4E-BP1 are
      distinct from those required for cap-complex assembly.

PMID- 9920864
TI  - Identification of a gene for a polyamine transport protein in yeast.
AB  - Properties of a membrane protein encoded by YLL028w were examined using yeast
      cells transformed with the gene. The transformed cells became resistant to
      polyamine toxicity, and the resistance was overcome by bafilomycin A1, an
      inhibitor of vacuolar H+-ATPase. Although spermine uptake activity of the
      transformed cells was almost the same as that of wild type cells, the uptake
      activity of vacuolar membrane vesicles from the transformed cells was higher than
      that from wild type cells. The transformed cells became resistant to MGBG
      (methylglyoxal bis(guanylhydrazone)) and paraquat, but not Ni2+ and Co2+,
      suggesting that the protein encoded by YLL028w is a transport protein specific
      for polyamines. When the YLL028w gene was disrupted by inserting the HIS3 gene,
      the cells became sensitive to polyamines, and spermine uptake activity of the
      vacuolar membrane vesicles decreased significantly. The accumulated spermine in
      YLL028w gene-disrupted cells decreased greatly compared with that in wild type
      cells. The results indicate that a membrane protein encoded by YLL028w (TPO1) is
      a polyamine transport protein on the vacuolar membrane.

PMID- 9920865
TI  - Enzyme activity of macrophage migration inhibitory factor toward oxidized
      catecholamines.
AB  - Macrophage migration inhibitory factor (MIF) is a relatively small, 12.5-kDa
      protein that is structurally related to some isomerases and for which multiple
      immune and catalytic roles have been proposed. MIF is widely expressed in tissues
      with particularly high levels in neural tissues. Here we show that MIF is able to
      catalyze the conversion of 3,4-dihydroxyphenylaminechrome and
      norepinephrinechrome, toxic quinone products of the neurotransmitter
      catecholamines 3,4-dihydroxyphenylamine and norepinephrine, to indoledihydroxy
      derivatives that may serve as precursors to neuromelanin. This raises the
      possibility that MIF participates in a detoxification pathway for catecholamine
      products and could therefore have a protective role in neural tissues, which as
      in Parkinson's disease, may be subject to catecholamine-related cell death.

PMID- 9920867
TI  - Interaction of Escherichia coli DNA polymerase I (Klenow fragment) with primer
      templates containing N-acetyl-2-aminofluorene or N-2-aminofluorene adducts in the
      active site.
AB  - DNA adducts formed by aromatic amines such as N-acetyl-2-aminofluorene (AAF) and
      N-2-aminofluorene (AF) are known to cause mutations by interfering with the
      process of DNA replication. To understand this phenomenon better, a gel
      retardation assay was used to measure the equilibrium dissociation constants for
      the binding of an exonuclease-deficient Escherichia coli DNA polymerase I (Klenow
      fragment) to DNA primer-templates modified with an AAF or AF adduct. The results
      indicate that the nature of the adduct as well as the presence and nature of an
      added dNTP have a significant influence on the strength of the binding of the
      polymerase to the DNA. More specifically, it was found that the binding is 5-10
      fold stronger when an AAF adduct, but not an AF adduct, is positioned in the
      enzyme active site. In addition, the polymerase was found to bind the unmodified
      primer-template less strongly in the presence of a noncomplementary dNTP than in
      the presence of the correct nucleotide. The same trend holds true for the primer
      template having an AF adduct, although the magnitude of this difference was
      lower. In the case of the AAF adduct, the interaction of the polymerase with the
      primer-template was stronger and almost independent of the nucleotide present.

PMID- 9920866
TI  - A newly identified horseshoe crab lectin with specificity for blood group A
      antigen recognizes specific O-antigens of bacterial lipopolysaccharides.
AB  - A 14-kDa lectin, named tachylectin-3, was newly identified from hemocytes of the
      Japanese horseshoe crab, Tachypleus tridentatus. This lectin exhibited
      hemagglutinating activity against human A-type erythrocytes, but not against the
      B- and O-types of erythrocytes and animal erythrocytes, including those of sheep,
      rabbit, horse, and bovine. The hemagglutinating activity of tachylectin-3 was
      equivalent to that of a previously identified lectin, named tachylectin-2, with
      affinity for N-acetyl-D-glucosamine or N-acetyl-D-galactosamine. However, the
      activity of tachylectin-3 was not inhibited by these two N-acetylhexosamines at
      100 mM but was inhibited by a blood group A-pentasaccharide at a minimum
      inhibitory concentration of 0.16 mM. Furthermore, the hemagglutinating activity
      was strongly inhibited by bacterial S-type lipopolysaccharides (LPSs) from Gram
      negative bacteria but not by R-type LPSs lacking O-antigens. One of the most
      effective S-type LPSs was from Escherichia coli O111:B4, with a minimum
      inhibitory concentration of 6 ng/ml. These data suggest that tachylectin-3
      specifically recognizes Gram-negative bacteria through the unique structural
      units of O-antigens. Ultracentrifugation analysis revealed that tachylectin-3 is
      present in dimer in solution. A cDNA coding for tachylectin-3 was isolated from a
      hemocyte cDNA library. Tachylectin-3 consisted of two repeating sequences, each
      with a partial sequence similarity to rinderpest virus neuraminidase. Tachylectin
      3 and three previously isolated types of tachylectins were all predominantly
      expressed in hemocytes and released from hemocytes in response to external
      stimuli. These lectins present at injured sites suggest that they probably serve
      synergistically to accomplish an effective host defense against invading
      microbes.

PMID- 9920868
TI  - Developmental regulation of the kappa locus involves both positive and negative
      sequence elements in the 3' enhancer that affect synergy with the intron
      enhancer.
AB  - Expression of the mouse immunoglobulin kappa locus is regulated by the intron and
      3' enhancers. Previously, we have reported that these enhancers can synergize at
      mature B cell stages. Here we present our recent studies on the identification
      and characterization of the 3' enhancer sequences that play important roles in
      this synergy. By performing mutational analyses with novel reporter constructs,
      we find that the 5' region of the cAMP response element (CRE), the PU. 1/PIP, and
      the E2A motifs of the 3' enhancer are critical for the synergy. These motifs are
      known to contribute to the enhancer activity. However, we also show that mutating
      other functionally important sequences has no significant effect on the synergy.
      Those sequences include the 3' region of the CRE motif, the BSAP motif, and the
      region 3' of the E2A motif. We have further demonstrated that either the 5'-CRE,
      the PU.1/PIP, or the E2A motif alone is sufficient to synergize with the intron
      enhancer. Moreover, the PU.1 motif appears to act as a negative element at pre-B
      cell stages but as a positive element at mature B cell stages. We have also
      identified a novel negative regulatory sequence within the 3' enhancer that
      contributes to the regulation of synergy, as well as developmental stage and
      tissue specificity of expression. While the levels of many of the 3' enhancer
      binding factors change very little in cell lines representing different B cell
      stages, the intron enhancer binding factors significantly increase at more mature
      B cell stages.

PMID- 9920869
TI  - Directed mutagenesis studies of the metal binding site at the subunit interface
      of Escherichia coli inorganic pyrophosphatase.
AB  - Recent crystallographic studies on Escherichia coli inorganic pyrophosphatase (E
      PPase) have identified three Mg2+ ions/enzyme hexamer in water-filled cavities
      formed by Asn24, Ala25, and Asp26 at the trimer-trimer interface (Kankare, J.,
      Salminen, T., Lahti, R., Cooperman, B., Baykov, A. A., and Goldman, A. (1996)
      Biochemistry 35, 4670-4677). Here we show that D26S and D26N substitutions
      decrease the stoichiometry of tight Mg2+ binding to E-PPase by approximately 0.5
      mol/mol monomer and increase hexamer stability in acidic medium. Mg2+ markedly
      decelerates the dissociation of enzyme hexamer into trimers at pH 5.0 and
      accelerates hexamer formation from trimers at pH 7.2 with wild type E-PPase and
      the N24D variant, in contrast to the D26S and D26N variants, when little or no
      effect is seen. The catalytic parameters describing the dependences of enzyme
      activity on substrate and Mg2+ concentrations are of the same magnitude for wild
      type E-PPase and the three variants. The affinity of the intertrimer site for
      Mg2+ at pH 7.2 is intermediate between those of two Mg2+ binding sites found in
      the E-PPase active site. It is concluded that the metal ion binding site found at
      the trimer-trimer interface of E-PPase is a high affinity site whose occupancy by
      Mg2+ greatly stabilizes the enzyme hexamer but has little effect on catalysis.

PMID- 9920870
TI  - Identification of an RcsA/RcsB recognition motif in the promoters of
      exopolysaccharide biosynthetic operons from Erwinia amylovora and Pantoea
      stewartii subspecies stewartii.
AB  - The regulation of capsule synthesis (Rcs) regulatory network is responsible for
      the induction of exopolysaccharide biosynthesis in many enterobacterial species.
      We have previously shown that two transcriptional regulators, RcsA and RcsB, do
      bind as a heterodimer to the promoter of amsG, the first reading frame in the
      operon for amylovoran biosynthesis in the plant pathogenic bacterium Erwinia
      amylovora. We now identified a 23-base pair fragment from position -555 to -533
      upstream of the translational start site of amsG as sufficient for the specific
      binding of the Rcs proteins. In addition, we could detect an RcsA/RcsB-binding
      site in a corresponding region of the promoter of cpsA, the homologous
      counterpart to the E. amylovora amsG gene in the operon for stewartan
      biosynthesis of Pantoea stewartii. The specificity and characteristic parameters
      of the protein-DNA interaction were analyzed by DNA retardation, protein-DNA
      cross-linking, and directed mutagenesis. The central core motif TRVGAAWAWTSYG of
      the amsG promoter was found to be most important for the specific interaction
      with RcsA/RcsB, as evaluated by mutational analysis and an in vitro selection
      approach. The wild type P. stewartii Rcs binding motif is degenerated in two
      positions and an up-mutation according to our consensus motif resulted in about a
      5-fold increased affinity of the RcsA/RcsB proteins.

PMID- 9920871
TI  - An electron spin resonance spin-trapping investigation of the free radicals
      formed by the reaction of mitochondrial cytochrome c oxidase with H2O2.
AB  - The reaction of purified bovine mitochondrial cytochrome c oxidase (CcO) and
      hydrogen peroxide was studied using the ESR spin-trapping technique. A protein
      centered radical adduct was trapped by 5, 5-dimethyl-1-pyrroline N-oxide and was
      assigned to a thiyl radical adduct based on its hyperfine coupling constants of
      aN = 14.7 G and abetaH = 15.7 G. The ESR spectra obtained using the nitroso spin
      traps 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS) and 2-methyl-2
      nitrosopropane (MNP) indicated that both DBNBS/.CcO and MNP/.CcO radical adducts
      are immobilized nitroxides formed by the trapping of protein-derived radicals.
      Alkylation of the free thiols on the enzyme with N-ethylmaleimide (NEM) prevented
      5, 5-dimethyl-1-pyrroline N-oxide adduct formation and changed the spectra of the
      MNP and DBNBS radical adducts. Nonspecific protease treatment of MNP-d9/.NEM-CcO
      converted its spectrum from that of an immobilized nitroxide to an isotropic
      three-line spectrum characteristic of rapid molecular motion. Super-hyperfine
      couplings were detected in this spectrum and assigned to the MNP/.tyrosyl
      adduct(s). The inhibition of either CcO or NEM-CcO with potassium cyanide
      prevented detectable MNP adduct formation, indicating heme involvement in the
      reaction. The results indicate that one or more cysteine residues are the
      preferred reductant of the presumed ferryl porphyrin cation radical residue
      intermediate. When the cysteine residues are blocked with NEM, one or more
      tyrosine residues become the preferred reductant, forming the tyrosyl radical.

PMID- 9920872
TI  - Architecture of a complex between the sigma70 subunit of Escherichia coli RNA
      polymerase and the nontemplate strand oligonucleotide. Luminescence resonance
      energy transfer study.
AB  - We used luminescence energy transfer measurements to determine the localization
      of 5'- and 3'-ends of a 12-nucleotide nontemplate strand oligonucleotide bound to
      sigma70 holoenzyme. Five single reactive cysteine mutants of sigma70 (cysteine
      residues at positions 1, 59, 366, 442, and 596) were labeled with a europium
      chelate fluorochrome (donor). The oligonucleotide was modified at the 5'- or at
      the 3'-end with Cy5 fluorochrome (acceptor). The energy transfer was observed
      upon complex formation between the donor-labeled sigma70 holoenzyme and the
      acceptor-labeled nontemplate strand oligonucleotide, whereas no interaction was
      observed with the template strand oligonucleotide. The oligonucleotide was bound
      in one preferred orientation. This observation together with the sequence
      specificity of single-stranded oligonucleotide interaction suggests that two
      mechanisms of discrimination between the template and nontemplate strand are used
      by sigma70: sequence specificity and strand polarity specificity. The bound
      oligonucleotide was found to be close to residue 442, confirming that the single
      stranded DNA binding site of sigma70 is located in an alpha-helix containing
      residue 442. The 5'-end of the oligonucleotide was oriented toward the COOH
      terminus of the helix.

PMID- 9920873
TI  - The reductive half-reaction of xanthine oxidase. Reaction with aldehyde
      substrates and identification of the catalytically labile oxygen.
AB  - The kinetics of xanthine oxidase has been investigated with the aim of addressing
      several outstanding questions concerning the reaction mechanism of the enzyme.
      Steady-state and rapid kinetic studies with the substrate 2,5
      dihydroxybenzaldehyde demonstrated that (kcat/Km)app and kred/Kd exhibit
      comparable bell-shaped pH dependence with pKa values of 6.4 +/- 0.2 and 8.4 +/-
      0.2, with the lower pKa assigned to an active-site residue of xanthine oxidase
      (possibly Glu-1261, by analogy to Glu-869 in the crystallographically known
      aldehyde oxidase from Desulfovibrio gigas) and the higher pKa to substrate. Early
      steps in the catalytic sequence have been investigated by following the reaction
      of the oxidized enzyme with a second aldehyde substrate, 2-aminopteridine-6
      aldehyde. The absence of a well defined acid limb in this pH profile and other
      data indicate that this complex represents an Eox.S rather than Ered.P complex
      (i.e. no chemistry requiring the active-site base has taken place in forming the
      long wavelength-absorbing complex seen with this substrate). It appears that
      xanthine oxidase (and by inference, the closely related aldehyde oxidases)
      hydroxylates both aromatic heterocycles and aldehydes by a mechanism involving
      base-assisted catalysis. Single-turnover experiments following incorporation of
      17O into the molybdenum center of the enzyme demonstrated that a single oxygen
      atom is incorporated at a site that gives rise to strong hyperfine coupling to
      the unpaired electron spin of the metal in the MoV oxidation state. By analogy to
      the hyperfine interactions seen in a homologous series of molybdenum model
      compounds, we conclude that this strongly coupled, catalytically labile site
      represents a metal-coordinated hydroxide rather than the Mo=O group and that this
      Mo-OH represents the oxygen that is incorporated into product in the course of
      catalysis.

PMID- 9920874
TI  - Carbon monoxide and cyanide as intrinsic ligands to iron in the active site of
      [NiFe]-hydrogenases. NiFe(CN)2CO, Biology's way to activate H2.
AB  - Infrared-spectroscopic studies on the [NiFe]-hydrogenase of Chromatium vinosum
      enriched in 15N or 13C, as well as chemical analyses, show that this enzyme
      contains three non-exchangeable, intrinsic, diatomic molecules as ligands to the
      active site, one carbon monoxide molecule and two cyanide groups. The results
      form an explanation for the three non-protein ligands to iron detected in the
      crystal structure of the Desulfovibrio gigas hydrogenase (Volbeda, A., Garcin,
      E., Piras, C., De Lacey, A. I., Fernandez, V. M., Hatchikian, E. C., Frey, M.,
      and Fontecilla-Camps, J. C. (1996) J. Am. Chem. Soc. 118, 12989-12996) and for
      the low spin character of the lone ferrous iron ion observed with Mossbauer
      spectroscopy (Surerus, K. K., Chen, M., Van der Zwaan, W., Rusnak, F. M., Kolk,
      M. , Duin, E. C., Albracht, S. P. J., and Munck, E. (1994) Biochemistry 33, 4980
      4993). The results do not support the notion, based upon studies of Desulfovibrio
      vulgaris [NiFe]-hydrogenase (Higuchi, Y., Yagi, T., and Noritake, Y. (1997)
      Structure 5, 1671-1680), that SO is a ligand to the active site. The occurrence
      of both cyanide and carbon monoxide as intrinsic constituents of a prosthetic
      group is unprecedented in biology.

PMID- 9920875
TI  - Cellobiose dehydrogenase from the fungi Phanerochaete chrysosporium and Humicola
      insolens. A flavohemoprotein from Humicola insolens contains 6-hydroxy-FAD as the
      dominant active cofactor.
AB  - Cellobiose dehydrogenases (CDH) were purified from cellulose-grown cultures of
      the fungi Phanerochaete chrysosporium and Humicola insolens. The pH optimum of
      the cellobiose-cytochrome c oxidoreductase activity of P. chrysosporium CDH was
      acidic, whereas that of H. insolens CDH was neutral. The absorption spectra of
      the two CDHs showed them to be typical hemoproteins, but there was a small
      difference in the visible region. Limited proteolysis between the heme and flavin
      domains was performed to investigate the cofactors. There was no difference in
      absorption spectrum between the heme domains of P. chrysosporium and H. insolens
      CDHs. The midpoint potentials of heme at pH 7.0 were almost identical, and no
      difference in pH dependence was observed over the range of pH 3-9. The pH
      dependence of cellobiose oxidation by the flavin domains was similar to that of
      the native CDHs, indicating that the difference in the pH dependence of the
      catalytic activity between the two CDHs is because of the flavin domains. The
      absorption spectrum of the flavin domain from H. insolens CDH has absorbance
      maxima at 343 and 426 and a broad absorption peak at 660 nm, whereas that of P.
      chrysosporium CDH showed a normal flavoprotein spectrum. Flavin cofactors were
      extracted from the flavin domains and analyzed by high-performance liquid
      chromatography. The flavin cofactor from H. insolens was found to be a mixture of
      60% 6-hydroxy-FAD and 40% FAD, whereas that from P. chrysosporium CDH was normal
      FAD. After reconstitution of the deflavo-proteins it was found that flavin
      domains containing 6-hydroxy-FAD were clearly active but their cellobiose
      oxidation rates were lower than those of flavin domains containing normal FAD.
      Reconstitution of flavin cofactor had no effect on the optimum pH. From these
      results, it is concluded that the pH dependence is not because of the flavin
      cofactor but is because of the protein molecule.

PMID- 9920876
TI  - In vivo architecture of the manganese superoxide dismutase promoter.
AB  - Mitochondrial manganese superoxide dismutase (Mn-SOD) is the primary cellular
      defense against damaging superoxide radicals generated by aerobic metabolism and
      as a consequence of inflammatory disease. Elevated expression of Mn-SOD therefore
      provides a potent cytoprotective advantage during acute inflammation. Mn-SOD
      contains a GC-rich and TATA/CAAT-less promoter characteristic of a housekeeping
      gene. In contrast, however, Mn-SOD expression is dramatically regulated in a
      variety of cells by numerous proinflammatory mediators, including
      lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1. To understand
      the underlying regulatory mechanisms controlling Mn-SOD expression, we utilized
      DNase I-hypersensitive (HS) site analysis, which revealed seven hypersensitive
      sites throughout the gene. Following high resolution DNase I HS site analysis,
      the promoter was found to contain five HS subsites, including a subsite that only
      appears following stimulus treatment. Dimethyl sulfate in vivo footprinting
      identified 10 putative constitutive protein-DNA binding sites in the proximal Mn
      SOD promoter as well as two stimulus-specific enhanced guanine residues possibly
      due to alterations in chromatin structure. In vitro footprinting data implied
      that five of the binding sites may be occupied by a combination of Sp1 and gut
      enriched Kr uppel-like factor. These studies have revealed the complex promoter
      architecture of a highly regulated cytoprotective gene.

PMID- 9920877
TI  - Characterization of genes encoding known and novel human mast cell tryptases on
      chromosome 16p13.3.
AB  - Tryptases are serine proteases implicated in asthma and are very highly expressed
      in human mast cells. They fall into two groups, alpha and beta. Although several
      related tryptase mRNAs are known, it is unclear which if any are transcripts of
      separate haploid genes. The studies described here investigated the nature and
      number of human tryptases and sought possibly novel members of the family. To
      this end, two human bacterial artificial chromosome (BAC) clones containing
      tryptase genes were identified and mapped to chromosome 16p13.3, of which
      approximately 2.2 megabases are syntenic with the part of mouse chromosome 17
      containing tryptase genes mouse mast cell protease (mMCP)-6 and -7. Sequencing
      and restriction mapping suggest that the BACs may partially overlap. Sequenced
      BAC genes correspond to three known beta-tryptases (betaI, betaII, and betaIII),
      an alpha-like gene, and a pair of novel hybrid genes related partly to alpha/beta
      tryptases and partly to orthologs of mMCP-7. betaII and betaIII, betaI and
      alphaII, as well as the two mMCP-7-like genes, may be alleles at single loci; in
      total, there are at least three nonallelic tryptase genes in the isolated BAC
      clones. DNA blotting and restriction analysis suggest that the BACs include most
      members of the immediate tryptase family. Thus, chromosome 16p13.3 harbors a
      cluster of known and previously undescribed members of the tryptase gene family.

PMID- 9920879
TI  - A reactivating factor for coenzyme B12-dependent diol dehydratase.
AB  - Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca undergoes
      suicide inactivation by glycerol, a physiological substrate. The coenzyme is
      modified through irreversible cleavage of its cobalt-carbon bond, resulting in
      inactivation of the enzyme by tight binding of the modified coenzyme to the
      active site. Recombinant DdrA and DdrB proteins of K. oxytoca were co-purified to
      homogeneity from cell-free extracts of Escherichia coli overexpressing the ddrAB
      genes. They existed as a tight complex, i.e. a putative reactivating factor, with
      an apparent molecular weight of 150,000. The factor consists of equimolar amounts
      of the two subunits with Mr of 64,000 (A) and 14,000 (B), encoded by the ddrA and
      ddrB genes, respectively. Therefore, its subunit structure is most likely A2B2.
      The factor not only reactivated glycerol-inactivated and O2-inactivated
      holoenzymes but also activated enzyme-cyanocobalamin complex in the presence of
      free adenosylcobalamin, ATP, and Mg2+. The reactivating factor mediated ATP
      dependent exchange of the enzyme-bound cyanocobalamin for free 5
      adeninylpentylcobalamin in the presence of ATP and Mg2+, but the reverse was not
      the case. Thus, it can be concluded that the inactivated holoenzyme becomes
      reactivated by exchange of the enzyme-bound, adenine-lacking cobalamins for free
      adenosylcobalamin, an adenine-containing cobalamin.

PMID- 9920878
TI  - The sizes of peptides generated from protein by mammalian 26 and 20 S
      proteasomes. Implications for understanding the degradative mechanism and antigen
      presentation.
AB  - Knowledge about the sizes of peptides generated by proteasomes during protein
      degradation is essential to fully understand their degradative mechanisms and the
      subsequent steps in protein turnover and generation of major histocompatibility
      complex class I antigenic peptides. We demonstrate here that 26 S and activated
      20 S proteasomes from rabbit muscle degrade denatured, nonubiquitinated proteins
      in a highly processive fashion but generate different patterns of peptides
      (despite their containing identical proteolytic sites). With both enzymes,
      products range in length from 3 to 22 residues, and their abundance decreases
      with increasing length according to a log-normal distribution. Less than 15% of
      the products are the length of class I presented peptides (8 or 9 residues), and
      two-thirds are too short to function in antigen presentation. Surprisingly, these
      mammalian proteasomes, which contain two "chymotryptic," two "tryptic," and two
      "post-acidic" active sites, generate peptides with a similar size distribution as
      do archaeal 20 S proteasomes, which have 14 identical sites. Furthermore,
      inactivation of the "tryptic" sites altered the peptides produced without
      significantly affecting their size distribution. Therefore, this distribution is
      not determined by the number, specificity, or arrangement of the active sites (as
      proposed by the "molecular ruler" model); instead, we propose that proteolysis
      continues until products are small enough to diffuse out of the proteasomes.

PMID- 9920880
TI  - Characterization of a silencer element and purification of a silencer protein
      that negatively regulates the human adenine nucleotide translocator 2 promoter.
AB  - Expression of adenine nucleotide translocator isoform 2 (ANT2) is growth
      regulated. In the present study, we report the presence of a silencer region in
      the human ANT2 promoter and the purification of a two-component factor that
      recognizes a specific hexanucleotide element, GTCCTG, of the silencer.
      Transfection of deletion constructs shows that ANT2 silencer activity extends
      over a region of at least 310 nts. However, mutating the GTCCTG element
      completely relieves silencing activity in the context of the human ANT2 promoter.
      The data suggest that the GTCCTG element might be required for maintaining
      silencer activity of the extended silencer region. The ANT2 silencer region
      cloned in front of the herpes simplex virus thymidine kinase promoter confers
      nearly complete inhibition to the heterologous promoter. However, unlike the ANT2
      promoter, mutating the GTCCTG element restores only partial activity to the
      herpes simplex virus thymidine kinase promoter. A protein complex consisting of
      two major polypeptides of 37 and 49 kDa was isolated from HeLa nuclear extracts
      by affinity chromatography using the GTCCTG element as the affinity resin. Cross
      linking studies and Southwestern analysis indicate that p37 binds DNA. p49
      appears to be loosely associated with the p37/DNA complex but is necessary for
      strong binding of p37. Our data implicating the GTCCTG element directly in
      silencing of the ANT2 promoter, together with data from the literature reporting
      the presence of this element within the silencer region of several additional
      promoters, suggest a general role of the GTCCTG element in transcriptional
      silencing.

PMID- 9920881
TI  - Transcription factor phosphorylation by pp90(rsk2). Identification of Fos kinase
      and NGFI-B kinase I as pp90(rsk2).
AB  - The in vitro phosphorylation of transcription factors by growth factor-activated
      protein kinases has resulted in the discovery of a number of activities whose
      identities and relationships to one another are unclear. Fos kinase is a growth
      factor-stimulated serine/threonine protein kinase that phosphorylates c-Fos at
      serine 362 within the carboxyl-terminal regulatory domain. Fos kinase activation
      is dependent on p21(ras) and mitogen-activated protein kinase/ERK kinase kinase
      (MEK) activity and is independent of phosphatidylinositol 3-kinase activity. We
      have purified Fos kinase by affinity chromatography using the Sepharose-linked
      protein kinase inhibitor, bisindolylmaleimide (BIM). Fos kinase has an apparent
      molecular mass of 88 kDa, and mass spectrophotometric analysis of the isolated
      protein showed that it produced tryptic fragments identical to those predicted
      for pp90(rsk2). Fos kinase isolated from nerve growth factor-stimulated PC12
      cells is indistinguishable from NGFI-B kinase I, based on their chromatographic
      behavior, substrate specificities, and relative sensitivity to BIM. Furthermore,
      we have distinguished Fos kinase from calcium/cAMP response element-binding
      protein (CREB) kinase. Therefore, Fos kinase and NGFI-B kinase I and pp90(rsk2)
      represent the same protein kinase species. Moreover, we report that pp90(rsk2)
      exists within nerve growth factor-stimulated PC12 cells as two
      chromatographically and immunologically distinct species. Finally, we demonstrate
      that CREB kinase is distinct from pp90(rsk2).

PMID- 9920883
TI  - Dependence of peroxisomal beta-oxidation on cytosolic sources of NADPH.
AB  - Growth of Saccharomyces cerevisiae with a fatty acid as carbon source was shown
      previously to require function of either glucose-6-phosphate dehydrogenase (ZWF1)
      or cytosolic NADP+-specific isocitrate dehydrogenase (IDP2), suggesting
      dependence of beta-oxidation on a cytosolic source of NADPH. In this study, we
      find that DeltaIDP2DeltaZWF1 strains containing disruptions in genes encoding
      both enzymes exhibit a rapid loss of viability when transferred to medium
      containing oleate as the carbon source. This loss of viability is not observed
      following transfer of a DeltaIDP3 strain lacking peroxisomal isocitrate
      dehydrogenase to medium with docosahexaenoate, a nonpermissive carbon source that
      requires function of IDP3 for beta-oxidation. This suggests that the fatty acid-
      phenotype of DeltaIDP2DeltaZWF1 strains is not a simple defect in utilization.
      Instead, we propose that the common function shared by IDP2 and ZWF1 is
      maintenance of significant levels of NADPH for enzymatic removal of the hydrogen
      peroxide generated in the first step of peroxisomal beta-oxidation in yeast and
      that inadequate levels of the reduced form of the cofactor can produce lethality.
      This proposal is supported by the finding that the sensitivity to exogenous
      hydrogen peroxide previously reported for DeltaZWF1 mutant strains is less
      pronounced when analyses are conducted with a nonfermentable carbon source, a
      condition associated with elevated expression of IDP2. Under those conditions,
      similar slow growth phenotypes are observed for DeltaZWF1 and DeltaIDP2 strains,
      and co-disruption of both genes dramatically exacerbates the H2O2s phenotype.
      Collectively, these results suggest that IDP2, when expressed, and ZWF1 have
      critical overlapping functions in provision of reducing equivalents for defense
      against endogenous or exogenous sources of H2O2.

PMID- 9920882
TI  - RhoA stimulates p27(Kip) degradation through its regulation of cyclin E/CDK2
      activity.
AB  - RhoA has been identified as an important regulator of cell proliferation. We
      recently showed that the Ras/RhoA pathway regulates the degradation of p27(Kip)
      and the progression of Chinese hamster embryo fibroblasts (IIC9 cells) through G1
      into S phase (Weber, J. D., Hu, W., Jefcoat, S. C., Raben, D. M., and Baldassare,
      J. J. (1997) J. Biol. Chem. 272, 32966-32971). In this report, we have
      demonstrated that, in IIC9 cells, RhoA regulates cyclin E/CDK2 activity, which is
      required for p27(Kip) degradation. As previously shown in several fibroblasts
      cell lines, expression of dominant-negative CDK2 in IIC9 cells blocked serum
      induced cyclin E/CDK2 activity and p27(Kip) degradation. In the absence of serum,
      expression of constitutively active RhoA(63) resulted in significant stimulation
      of cyclin E/CDK2 activity and degradation of p27(Kip). Cotransfection of dominant
      negative CDK2 and RhoA(63) inhibited RhoA(63)-induced cyclin E/CDK2 activity and
      p27(Kip) degradation. In addition, expression of dominant-negative RhoA blocked
      serum-induced cyclin E/CDK2 activity and p27(Kip) degradation. Finally,
      expression of catalytically active cyclin E/CDK2 rescued the effect of expression
      of dominant-negative RhoA. Taken together, these data show that RhoA regulates
      p27(Kip) degradation through its regulation of cyclin E/CDK2 activity.

PMID- 9920884
TI  - The family of cold shock proteins of Bacillus subtilis. Stability and dynamics in
      vitro and in vivo.
AB  - Bacillus subtilis possesses three homologous small cold shock proteins (CSPs;
      CspB, CspC, CspD, sequence identity >72%). They share a similar beta-sheet
      structure, as shown by circular dichroism, and have a very low conformational
      stability, with CspC being the least stable. Similar to CspB, CspC and CspD
      unfold and refold extremely fast in a N <==> U two-state reaction with average
      lifetimes of only 100-150 ms for the native state and 1-6 ms for the unfolded
      states at 25 degreesC. As a consequence of their low stability and low kinetic
      protection against unfolding, all three cold shock proteins are rapidly degraded
      by proteases in vitro. Analysis of the CSP stabilities in vivo by pulse-chase
      experiments revealed that CspB and CspD are stable during logarithmic growth at
      37 degreesC as well as after cold shock. The cellular half-life of CspC is
      shortened at 37 degreesC, but under cold shock conditions CspC becomes stable.
      The proteolytic susceptibility of the CSPs in vitro was strongly reduced in the
      presence of a nucleic acid ligand, suggesting that the observed stabilization of
      CSPs in vivo is mediated by binding to their substrate mRNA at 37 degreesC and,
      in particular, under cold shock conditions.

PMID- 9920885
TI  - Regulation of Cl-/ HCO3- exchange by cystic fibrosis transmembrane conductance
      regulator expressed in NIH 3T3 and HEK 293 cells.
AB  - A central function of cystic fibrosis transmembrane conductance regulator (CFTR)
      expressing tissues is the secretion of fluid containing 100-140 mM HCO3-. High
      levels of HCO3- maintain secreted proteins such as mucins (all tissues) and
      digestive enzymes (pancreas) in a soluble and/or inactive state. HCO3- secretion
      is impaired in CF in all CFTR-expressing, HCO3--secreting tissues examined. The
      mechanism responsible for this critical problem in CF is unknown. Since a major
      component of HCO3- secretion in CFTR-expressing cells is mediated by the action
      of a Cl-/HCO3- exchanger (AE), in the present work we examined the regulation of
      AE activity by CFTR. In NIH 3T3 cells stably transfected with wild type CFTR and
      in HEK 293 cells expressing WT and several mutant CFTR, activation of CFTR by
      cAMP stimulated AE activity. Pharmacological and mutagenesis studies indicated
      that expression of CFTR in the plasma membrane, but not the Cl- conductive
      function of CFTR was required for activation of AE. Furthermore, mutations in
      NBD2 altered regulation of AE activity by CFTR independent of their effect on Cl-
      channel activity. At very high expression levels CFTR modified the sensitivity of
      AE to 4,4'-diisothiocyanatostilbene-2, 2'-disulfonate. The novel finding of
      regulation of Cl-/HCO3- exchange by CFTR reported here may have important
      physiological implications and explain, at least in part, the impaired HCO3-
      secretion in CF.

PMID- 9920886
TI  - Primary structure and functional characteristics of a mammalian sodium-coupled
      high affinity dicarboxylate transporter.
AB  - We have cloned a Na+-dependent, high affinity dicarboxylate transporter (NaDC3)
      from rat placenta. NaDC3 exhibits 48% identity in amino acid sequence with rat
      NaDC1, a Na+-dependent, low affinity dicarboxylate transporter. NaDC3-specific
      mRNA is detectable in kidney, brain, liver, and placenta. When expressed in
      mammalian cells, NaDC3 mediates Na+-dependent transport of succinate with a Kt of
      2 microM. The transport function of NaDC3 shows a sigmoidal relationship with
      regard to Na+ concentration, with a Hill coefficient of 2.7. NaDC3 accepts a
      number of dicarboxylates including dimethylsuccinate as substrates and excludes
      monocarboxylates. Li+ inhibits NaDC3 in the presence of Na+. Transport of
      succinate by NaDC3 is markedly influenced by pH, the transport function gradually
      decreasing when pH is acidified from 8. 0 to 5.5. In contrast, the influence of
      pH on NaDC3-mediated transport of citrate is biphasic in which a pH change from
      8.0 to 6. 5 stimulates the transport and any further acidification inhibits the
      transport. In addition, the potency of citrate to compete with NaDC3-mediated
      transport of succinate increases 25-fold when pH is changed from 7.5 to 5.5.
      These data show that NaDC3 interacts preferentially with the divalent anionic
      species of citrate. This represents the first report on the cloning and
      functional characterization of a mammalian Na+-dependent, high affinity
      dicarboxylate transporter.

PMID- 9920887
TI  - Estrogen receptor reduces CYP1A1 induction in cultured human endometrial cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exerts its toxic action via the aryl
      hydrocarbon (Ah) receptor, which induces a battery of xenobiotic-metabolizing
      enzymes, including the cytochrome P450 isozyme, CYP1A1. TCDD-induced 7
      ethoxycoumarin-O-deethylase activity was reduced 75% in cultured human
      endometrial ECC-1 cells exposed to various concentrations of 17beta-estradiol for
      up to 72 h, with a half-maximal effective concentration (EC50) of 0.9 nM. Reduced
      enzyme activity was correlated with decreased CYP1A1 mRNA levels, and
      transcription. Exposure to TCDD plus 17beta-estradiol also reduced CYP1A1
      activity in MCF-7 breast cancer cells but not in Hep-3B human liver cells or HuE
      primary human keratinocytes, suggesting that the effect was specific to estrogen
      regulated cells. Estrogen receptor antagonists 4-hydroxytamoxifen and 7alpha-[9
      (4,4, 5,5,5-pentafluoro-pentylsulfinyl)nonyl]estra-1,3,5(10)-tr iene3, 17beta
      diol restored TCDD-induced CYP1A1 transcription, steady-state mRNA levels, and
      enzymatic activity in ECC-1 cells. Gel mobility shift assay showed that 17beta
      estradiol had little effect on Ah receptor binding to its DNA-responsive element.
      17beta-Estradiol did not alter the induction of another Ah receptor-regulated
      gene, CYP1B1, suggesting that altered Ah receptor binding to DNA does not mediate
      reduced CYP1A1 transcription. Transfecting ECC-1 cells with a general
      transcription factor involved in CYP1A1 induction, nuclear factor-1, reversed
      17beta-estradiol antagonism of dioxin induced-CYP1A1. The data suggest that
      17beta-estradiol reduced CYP1A1 expression at the transcriptional level by
      squelching available nuclear factor-1, a transcription factor that interacts with
      both Ah and estrogen receptors.

PMID- 9920888
TI  - Identification of a domain of Axin that binds to the serine/threonine protein
      phosphatase 2A and a self-binding domain.
AB  - Axin is a negative regulator of embryonic axis formation in vertebrates, which
      acts through a Wnt signal transduction pathway involving the serine/threonine
      kinase GSK-3 and beta-catenin. Axin has been shown to have distinct binding sites
      for GSK-3 and beta-catenin and to promote the phosphorylation of beta-catenin and
      its consequent degradation. This provides an explanation for the ability of Axin
      to inhibit signaling through beta-catenin. In addition, a more N-terminal region
      of Axin binds to adenomatous polyposis coli (APC), a tumor suppressor protein
      that also regulates levels of beta-catenin. Here, we report the results of a
      yeast two-hybrid screen for proteins that interact with the C-terminal third of
      Axin, a region in which no binding sites for other proteins have previously been
      identified. We found that Axin can bind to the catalytic subunit of the
      serine/threonine protein phosphatase 2A through a domain between amino acids 632
      and 836. This interaction was confirmed by in vitro binding studies as well as by
      co-immunoprecipitation of epitope-tagged proteins expressed in cultured cells.
      Our results suggest that protein phosphatase 2A might interact with the
      Axin.APC.GSK-3.beta-catenin complex, where it could modulate the effect of GSK-3
      on beta-catenin or other proteins in the complex. We also identified a region of
      Axin that may allow it to form dimers or multimers. Through two-hybrid and co
      immunoprecipitation studies, we demonstrated that the C-terminal 100 amino acids
      of Axin could bind to the same region as other Axin molecules.

PMID- 9920889
TI  - Kinetic and thermodynamic analysis of mutant type II DNA topoisomerases that
      cannot covalently cleave DNA.
AB  - DNA topoisomerase II catalyzes two different chemical reactions as part of its
      DNA transport cycle: ATP hydrolysis and DNA breakage/religation. The coordination
      between these reactions was studied using mutants of yeast topoisomerase II that
      are unable to covalently cleave DNA. In the absence of DNA, the ATPase activities
      of these mutant enzymes are identical to the wild type activity. DNA binding
      stimulates the ATPase activity of the mutant enzymes, but with steady-state
      parameters different from those of the wild type enzyme. These differences were
      examined through DNA binding experiments and pre-steady-state ATPase assays. One
      mutant protein, Y782F, binds DNA with the same affinity as wild type protein.
      This mutant topologically traps one DNA circle in the presence of a
      nonhydrolyzable ATP analog under the same conditions that the wild type protein
      catenates two circles. Rapid chemical quench and pulse-chase ATPase experiments
      reveal that the mutant proteins bound to DNA have the same sequential hydrolysis
      reaction cycle as the wild type enzyme. Binding of ATP to the mutants is not
      notably impaired, but hydrolysis of the first ATP is slower than for the wild
      type enzyme. Models to explain these results in the context of the entire DNA
      topoisomerase II reaction cycle are discussed.

PMID- 9920890
TI  - The requirement for molecular chaperones during endoplasmic reticulum-associated
      protein degradation demonstrates that protein export and import are
      mechanistically distinct.
AB  - Polypeptide import into the yeast endoplasmic reticulum (ER) requires two hsp70s,
      Ssa1p in the cytosol and BiP (Kar2p) in the ER lumen. After import, aberrant
      polypeptides may be exported to the cytoplasm for degradation by the proteasome,
      and defects in the ER chaperone calnexin (Cne1p) compromise their degradation.
      Both import and export require BiP and the Sec61p translocation complex,
      suggesting that import and export may be mechanistically related. We now show
      that the cne1Delta and two kar2 mutant alleles exhibit a synthetic interaction
      and that the export and degradation of pro-alpha factor is defective in kar2
      mutant microsomes. Pulse-chase analysis indicates that A1PiZ, another substrate
      for degradation, is stabilized in the kar2 strains at the restrictive
      temperature. Because two of the kar2 mutants examined are proficient for
      polypeptide import, the roles of BiP during ER protein export and import differ,
      indicating that these processes must be mechanistically distinct. To examine
      whether Ssa1p drives polypeptides from the ER and is also required for
      degradation, we assembled reactions using strains either containing a mutation in
      SSA1 or in which the level of Ssa1p could be regulated. We found that pro-alpha
      factor and A1PiZ were degraded normally, indicating further that import and
      export are distinct and that other cytosolic factors may pull polypeptides from
      the ER.

PMID- 9920891
TI  - Cloning of a surface membrane glycoprotein specific for the infective form of
      Trypanosoma cruzi having adhesive properties to laminin.
AB  - Trypomastigotes of Trypanosoma cruzi express a set of surface glycoproteins
      known, collectively, as Tc-85. A monoclonal antibody to these proteins, named
      H1A10, inhibits (50-90%) in vitro parasite interiorization into host cells, thus
      implicating these glycoproteins in the infection process. Two DNA inserts, a
      genomic DNA fragment and a full-length cDNA encoding the H1A10 epitope, have now
      been cloned and characterized. Results show that both have high sequence identity
      with all reported members of the gp85/trans-sialidase gene family, although the
      H1A10 epitope exists only in the Tc-85 subset of the family. The epitope has been
      mapped by competition of antibody binding to a Tc-85 recombinant protein with
      peptides having sequences predicted by the Tc-85 DNA sequence, which contains
      also putative N-glycosylation sites and COOH-terminal
      glycosylphosphatidylinositol anchor insertion sites, as expected, since an N
      glycan chain and a glycosylphosphatidylinositol anchor have been characterized
      previously in the Tc-85 subset. The protein encoded by the full-length cDNA
      insert binds to cells and in vitro to laminin, but not to gelatin or fibronectin,
      in a saturable manner. For the first time it was possible to assign a defined
      ligand to a sequenced glycoprotein belonging to the gp85 family. This fact,
      together with the reported binding of family members to cell surfaces, reinforces
      the hypothesis that this family encodes glycoproteins with similar sequences but
      differing enough as to bind to different ligands and thus forming a family of
      adhesion glycoproteins enabling the parasite to overcome the barriers interposed
      by cell membranes, extracellular matrices, and basal laminae.

PMID- 9920892
TI  - A human tyrosine hydroxylase isoform associated with progressive supranuclear
      palsy shows altered enzymatic activity.
AB  - A novel human tyrosine hydroxylase (HTH) messenger RNA subgroup generated by
      alternative splicing and characterized by the absence of the third exon was
      recently identified. The corresponding putative protein lacks 74 amino acids
      including Ser31 and Ser40, two major phosphorylation sites implicated in the
      regulation of HTH activity. These mRNA species are detected in adrenal medulla
      and are overexpressed in patients suffering from progressive supranuclear palsy,
      a neurodegenerative disease mostly affecting catecholaminergic neurons of the
      basal ganglia. In the present work, an HTH protein isoform lacking exon 3 was
      identified in human adrenal medulla. For this purpose, an antibody was raised
      against the HTH exon 3. The effect of the removal of exon 3 on the enzymatic
      activity of HTH was studied in vitro by comparing a purified recombinant fusion
      protein without exon 3 (glutathione S-transferase (GST)-HTHDelta3) to the
      equivalent protein containing exon 3 (GST-HTH3). In initial velocity conditions,
      GST-HTHDelta3 has 30% of the maximal velocity of GST-HTH3. Moreover, the skipping
      of exon 3 results in the absence of activation of GST-HTH by heparin and
      increases by 10-fold the retroinhibition constant for dopamine, demonstrating the
      involvement of exon 3 in the regulation of HTH enzymatic activity. The
      identification of a variably expressed HTH isoform that lacks an exon implicated
      in activity regulation supports the view that HTH alternative splicing
      contributes to the functional diversity within the catecholaminergic system and
      may be implicated in some neurological diseases.

PMID- 9920893
TI  - Inositol 1,4,5-trisphosphate receptor down-regulation is activated directly by
      inositol 1,4,5-trisphosphate binding. Studies with binding-defective mutant
      receptors.
AB  - Activation of certain phosphoinositidase C-linked cell surface receptors is known
      to cause an acceleration of the proteolysis of inositol 1,4,5-trisphosphate
      (InsP3) receptors and, thus, lead to InsP3 receptor down-regulation. To gain
      insight into this process, we examined whether or not InsP3 receptor degradation
      is a direct consequence of InsP3 binding by analyzing the down-regulation of
      exogenous wild-type and binding-defective mutant InsP3 receptors expressed in SH
      SY5Y human neuroblastoma cells. Stimulation of these cells with carbachol showed
      that wild-type exogenous receptors could be down-regulated but that the binding
      defective mutant exogenous receptors were not. Thus, InsP3 binding appears to
      mediate down-regulation. To validate this conclusion, a comprehensive analysis of
      the effects of the exogenous receptors was undertaken. This showed that exogenous
      receptors (i) are localized appropriately within the cell, (ii) enhance InsP3
      induced Ca2+ release in permeabilized cells, presumably by increasing the number
      of InsP3-sensitive Ca2+ channels, (iii) have minimal effects on Ca2+ mobilization
      and InsP3 formation in intact cells, (iv) form heteromers with endogenous
      receptors, and (v) do not alter the down-regulation of endogenous receptors. In
      total, these data show that the introduction of exogenous receptors into SH-SY5Y
      cells does not compromise intracellular signaling or the down-regulatory process.
      We can thus conclude that InsP3 binding directly activates InsP3 receptor
      degradation. Because InsP3 binding induces a conformational change in the InsP3
      receptor, these data suggest that this change provides the signal for accelerated
      proteolysis.

PMID- 9920894
TI  - Phosphorylation-dependent inhibition of protein phosphatase-1 by G-substrate. A
      Purkinje cell substrate of the cyclic GMP-dependent protein kinase.
AB  - G-substrate, a specific substrate of the cGMP-dependent protein kinase, has
      previously been localized to the Purkinje cells of the cerebellum. We report here
      the isolation from mouse brain of a cDNA encoding G-substrate. This cDNA was used
      to localize G-substrate mRNA expression, as well as to produce recombinant
      protein for the characterization of G-substrate phosphatase inhibitory activity.
      Brain and eye were the only tissues in which a G-substrate transcript was
      detected. Within the brain, G-substrate transcripts were restricted almost
      entirely to the Purkinje cells of the cerebellum, although transcripts were also
      detected at low levels in the paraventricular region of the hypothalamus and the
      pons/medulla. Like the native protein, the recombinant protein was preferentially
      phosphorylated by cGMP-dependent protein kinase (Km = 0.2 microM) over cAMP
      dependent protein kinase (Km = 2.0 microM). Phospho-G-substrate inhibited the
      catalytic subunit of native protein phosphatase-1 with an IC50 of 131 +/- 27 nM.
      Dephospho-G-substrate was not found to be inhibitory. Both dephospho- and phospho
      G-substrate were weak inhibitors of native protein phosphatase-2A1, which
      dephosphorylated G-substrate 20 times faster than the catalytic subunit of
      protein phosphatase-1. G-substrate potentiated the action of cAMP-dependent
      protein kinase on a cAMP-regulated luciferase reporter construct, consistent with
      an inhibition of cellular phosphatases in vivo. These results provide the first
      demonstration that G-substrate inhibits protein phosphatase-1 and suggest a novel
      mechanism by which cGMP-dependent protein kinase I can regulate the activity of
      the type 1 protein phosphatases.

PMID- 9920895
TI  - An additional region of coactivator GRIP1 required for interaction with the
      hormone-binding domains of a subset of nuclear receptors.
AB  - Transcriptional coactivators of the p160 family (SRC-1, GRIP1, and p/CIP)
      associate with DNA-bound nuclear receptors (NRs) and help the NRs to recruit an
      active transcription initiation complex to the promoters of target genes.
      Previous studies have demonstrated the importance of the NR interaction domain
      (NID) of p160 proteins containing three NR box motifs (LXXLL) for the interaction
      with the hormone-binding domains of NRs. Here we report that, in addition to NID,
      another region of coactivator GRIP1 (amino acids 1011-1121), called the auxiliary
      NID (NIDaux), is required in vitro and in vivo for efficient interaction with a
      subset of NRs, including the glucocorticoid receptor (GR), androgen receptor, and
      retinoic acid receptor alpha. A second group of NRs, which includes the
      progesterone receptor, retinoid X receptor alpha, thyroid hormone receptor beta1,
      and vitamin D receptor, required only NID for efficient interaction. For binding
      to GR, the NID and NIDaux of GRIP1 must act in cis, but deletion of up to 144
      amino acids between the two regions did not reduce binding efficiency. Amino
      acids 1011-1121 of GRIP1 also contain a p300 interaction domain, but mutational
      analysis indicated that the p300 interaction function within this region is
      separable from the ability to contribute to GR hormone-binding domain binding.
      SRC-1 lacks an NIDaux activity equivalent to that in GRIP1.

PMID- 9920896
TI  - The structure of the site on adenovirus early region 1A responsible for binding
      to TATA-binding protein determined by NMR spectroscopy.
AB  - Previous detailed mutational analysis has shown that the binding site on
      adenovirus (Ad) early region 1A (E1A) for TATA-binding protein (TBP) is located
      toward the N terminus of conserved region 3 (CR3). Here we demonstrate that
      synthetic peptides of between 15 and 22 amino acids, identical to amino acid
      sequences of CR3 present in the larger Ad5 E1A (13 S product) and in both the
      Ad12 E1A (13 and 12 S products) proteins that lie N-terminal to the zinc finger
      motif, can disrupt binding of E1A to TBP. These findings suggest that the
      peptides are biologically active in terms of interacting with TBP and must
      therefore comprise some, if not all, of the TBP binding site on E1A. The
      interaction between Ad12 E1A and TBP was confirmed by direct co-precipitation
      experiments. In 1H NMR studies of CR3 peptides, regular patterns of NOEs were
      observed from which their conformational preferences in aqueous solution were
      determined. Both Ad5 and Ad12 peptides were shown to contain regions of helical
      backbone structure in 50% trifluoroethanol. In each case, the type and
      intensities of NOE cross-peaks observed correlated best to alpha-helical turns.
      These helices are more extensive in larger peptides and extend from Glu141 to
      Val147 and from Arg144 to Pro152 in the full-length Ad5 and Ad12 13S E1A
      proteins, respectively. The structure of a 19-residue Ad5 CR3 peptide carrying
      the V147L mutation in the full-length protein that abolishes TBP binding was
      examined. No significant differences between the substituted and wild type
      peptides were observed, suggesting that this substitution in the intact protein
      may cause disruption of global rather than local structures.

PMID- 9920897
TI  - A peptide inhibiting the collagen binding function of integrin alpha2I domain.
AB  - Integrin alpha2 subunit forms in the complex with the beta1 subunit a cell
      surface receptor binding extracellular matrix molecules, such as collagens and
      laminin-1. It is a receptor for echovirus-1, as well. Ligands are recognized by
      the special "inserted" domain (I domain) in the integrin alpha2 subunit. Venom
      from a pit viper, Bothrops jararaca, has been shown to inhibit the interaction of
      platelet alpha2beta1 integrin with collagen because of the action of a
      disintegrin/metalloproteinase named jararhagin. The finding that crude B.
      jararaca venom could prevent the binding of human recombinant ralpha2I domain to
      type I collagen led us to study jararhagin further. Synthetic peptides
      representing hydrophilic and charged sequences of jararhagin, including the RSECD
      sequence replacing the well known RGD motif in the disintegrin-like domain, were
      synthesized. Although the disintegrin-like domain derived peptides failed to
      inhibit ralpha2I domain binding to collagen, a basic peptide from the
      metalloproteinase domain proved to be functional. In an in vitro assay, the
      cyclic peptide, CTRKKHDNAQC, was shown to bind strongly to human recombinant
      alpha2I domain and to prevent its binding to type I and IV collagens and to
      laminin-1. Mutational analysis indicated that a sequence of three amino acids,
      arginine-lysine-lysine (RKK), is essential for ralpha2I domain binding, whereas
      the mutation of the other amino acids in the peptide had little if any effect on
      its binding function. Importantly, the peptide was functional only in the cyclic
      conformation and its affinity was strictly dependent on the size of the cysteine
      constrained loop. Furthermore, the peptide could not bind to alpha2I domain in
      the absence of Mg2+, suggesting that the conformation of the I domain was
      critical, as well. Cells could attach to the peptide only if they expressed
      alpha2beta1 integrin, and the attachment was inhibited by anti-integrin
      antibodies.

PMID- 9920898
TI  - Distinct and common pathways in the regulation of insulin-like growth factor-1
      receptor gene expression by angiotensin II and basic fibroblast growth factor.
AB  - Angiotensin II (Ang II) and basic fibroblast growth factor (bFGF) are important
      modulators of cell growth under physiological and pathophysiological conditions.
      We and others have previously shown that these growth factors increase insulin
      like growth factor-1 receptor (IGF-1R) number and mRNA in vascular smooth muscle
      cells and that this effect is transcriptionally regulated. To study the
      mechanisms and the signaling pathways involved, IGF-1R promoter reporter
      constructs were transiently transfected in CHO-AT1 cells that overexpress
      angiotensin AT1 receptors. Our findings indicate that Ang II and bFGF
      significantly increased IGF-1R promoter activity up to 7- and 3-fold,
      respectively. The effect induced by Ang II was mediated via a tyrosine kinase
      dependent mechanism, since tyrphostin A25 largely inhibited the Ang II-induced
      increase in promoter activity. In addition, co-transfection of dominant negative
      Ras, Raf, and MEK1 or pretreatment with the MEK inhibitor PD 98059 dose
      dependently decreased both the Ang II- and bFGF-induced increase in IGF-1R
      transcription and protein expression, suggesting that the Ras-Raf-mitogen
      activated protein kinase kinase pathway is required for both growth factors.
      Reactive oxygen species have been shown to act as second messengers in Ang II
      induced signaling, and activation of the transcription factor NF-kappaB is redox
      sensitive. While co-transfection of dominant negative IkappaBalpha mutant
      completely inhibited the Ang II-induced increase in transcription, it had no
      effect on the bFGF signaling. In contrast, co-transfection studies indicated that
      the transcription factors STAT1, STAT3, and c-Jun and the Janus kinase 2 kinase
      are required in the signaling pathway of bFGF, whereas only dominant c-Jun
      inhibited the Ang II-induced effect. In summary, these data demonstrate that Ang
      II and bFGF increase IGF-1R gene transcription via distinct as well as shared
      pathways and have important implications for understanding growth-stimulatory
      effects of these growth factors on vascular cells.

PMID- 9920899
TI  - Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic
      activity.
AB  - Metalloprotease disintegrins are a family of membrane-anchored glycoproteins that
      are known to function in fertilization, myoblast fusion, neurogenesis, and
      ectodomain shedding of tumor necrosis factor (TNF)-alpha. Here we report the
      analysis of the intracellular maturation and catalytic activity of the widely
      expressed metalloprotease disintegrin MDC9. Our results suggest that the pro
      domain of MDC9 is removed by a furin-type pro-protein convertase in the secretory
      pathway before the protein emerges on the cell surface. The soluble
      metalloprotease domain of MDC9 cleaves the insulin B-chain, a generic protease
      substrate, providing the first evidence that MDC9 is catalytically active.
      Soluble MDC9 appears to have distinct specificities for cleaving candidate
      substrate peptides compared with the TNF-alpha convertase (TACE/ADAM17). The
      catalytic activity of MDC9 can be inhibited by hydroxamic acid-type
      metalloprotease inhibitors in the low nanomolar range, in one case with up to 50
      fold selectivity for MDC9 versus TACE. Peptides mimicking the predicted cysteine
      switch region of MDC9 or TACE inhibit both enzymes in the low micromolar range,
      providing experimental evidence for regulation of metalloprotease disintegrins
      via a cysteine-switch mechanism. Finally, MDC9 is shown to become phosphorylated
      when cells are treated with the phorbol ester phorbol 12-myristate 13-acetate, a
      known inducer of protein ectodomain shedding. This work implies that removal of
      the inhibitory pro-domain of MDC9 by a furin-type pro-protein convertase in the
      secretory pathway is a prerequisite for protease activity. After pro-domain
      removal, additional steps, such as protein kinase C-dependent phosphorylation,
      may be involved in regulating the catalytic activity of MDC9, which is likely to
      target different substrates than the related TNF-alpha-convertase.

PMID- 9920900
TI  - Bioenergetics of the staphylococcal multidrug export protein QacA. Identification
      of distinct binding sites for monovalent and divalent cations.
AB  - The multidrug efflux pump QacA from Staphylococcus aureus confers resistance to
      an extensive range of structurally dissimilar compounds. Fluorimetric analyses
      demonstrated that QacA confers resistance to the divalent cation 4',6-diamidino-2
      phenylindole, utilizing a proton motive force-dependent efflux mechanism
      previously demonstrated for QacA-mediated resistance to the monovalent cation
      ethidium. Both the ionophores nigericin and valinomycin inhibited QacA-mediated
      export of ethidium, indicating an electrogenic drug/nH+ (n >/= 2) antiport
      mechanism. The kinetic parameters, Km and Vmax, were determined for QacA-mediated
      export of four fluorescent substrates, 4',6-diamidino-2-phenylindole, 3', 3'
      dipropyloxacarbocyanine, ethidium, and pyronin Y. Competition studies showed that
      QacA-mediated ethidium export is competitively inhibited by monovalent cations,
      e.g. benzalkonium, and non-competitively inhibited by divalent cations, e.g.
      propamidine, which suggests that monovalent and divalent cations bind at distinct
      sites on the QacA protein. The quaternary ammonium salt, 1-(4
      trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene, was used as a membrane
      specific fluorescence probe and demonstrated that the amount of substrate
      entering the inner leaflet was significantly reduced in QacA-containing strains,
      supporting the notion that the substrate is extruded directly from the membrane.

PMID- 9920902
TI  - Identification of residues lining the translocation pore of human AE1, plasma
      membrane anion exchange protein.
AB  - AE1 is the chloride/bicarbonate anion exchanger of the erythrocyte plasma
      membrane. We have used scanning cysteine mutagenesis and sulfhydryl-specific
      chemistry to identify pore-lining residues in the Ser643-Ser690 region of the
      protein. The Ser643-Ser690 region spans transmembrane segment 8 of AE1 and
      surrounds Glu681, which may reside at the transmembrane permeability barrier.
      Glu681 also directly interacts with some anions during anion transport. The
      introduced cysteine mutants were expressed by transient transfection of HEK293
      cells. Anion exchange activity was assessed by measurement of changes of
      intracellular pH, which follow transmembrane bicarbonate movement mediated by
      AE1. To identify residues that might form part of an aqueous transmembrane pore,
      we measured anion exchange activity of each introduced cysteine mutant before and
      after incubation with the sulfhydryl reagents para-chloromercuribenzene sulfonate
      and 2-(aminoethyl)methanethiosulfonate hydrobromide. Our data identified
      transmembrane mutants A666C, S667C, L669C, L673C, L677C, and L680C and
      intracellular mutants I684C and I688C that could be inhibited by sulfhydryl
      reagents and may therefore form a part of a transmembrane pore. These residues
      map to one face of a helical wheel plot. The ability to inhibit two intracellular
      mutants suggests that transmembrane helix 8 extends at least two helical turns
      beyond the intracellular membrane surface. The identified hydrophobic pore-lining
      residues (leucine, isoleucine, and alanine) may limit interactions with substrate
      anions.

PMID- 9920901
TI  - RGS proteins determine signaling specificity of Gq-coupled receptors.
AB  - Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by
      Galpha subunits, thereby attenuating signaling. RGS4 is a GTPase-activating
      protein for Gi and Gq class alpha subunits. In the present study, we used
      knockouts of Gq class genes in mice to evaluate the potency and selectivity of
      RGS4 in modulating Ca2+ signaling transduced by different Gq-coupled receptors.
      RGS4 inhibited phospholipase C activity and Ca2+ signaling in a receptor
      selective manner in both permeabilized cells and cells dialyzed with RGS4 through
      a patch pipette. Receptor-dependent inhibition of Ca2+ signaling by RGS4 was
      observed in acini prepared from the rat and mouse pancreas. The response of mouse
      pancreatic acini to carbachol was about 4- and 33-fold more sensitive to RGS4
      than that of bombesin and cholecystokinin (CCK), respectively. RGS1 and RGS16
      were also potent inhibitors of Gq-dependent Ca2+ signaling and acted in a
      receptor-selective manner. RGS1 showed approximately 1000-fold higher potency in
      inhibiting carbachol than CCK-dependent signaling. RGS16 was as effective as RGS1
      in inhibiting carbachol-dependent signaling but only partially inhibited the
      response to CCK. By contrast, RGS2 inhibited the response to carbachol and CCK
      with equal potency. The same pattern of receptor-selective inhibition by RGS4 was
      observed in acinar cells from wild type and several single and double Gq class
      knockout mice. Thus, these receptors appear to couple Gq class alpha subunit
      isotypes equally. Difference in receptor selectivity of RGS proteins action
      indicates that regulatory specificity is conferred by interaction of RGS proteins
      with receptor complexes.

PMID- 9920903
TI  - Regulation of the c-met proto-oncogene promoter by p53.
AB  - In the present study, we have investigated the possible involvement of p53 in the
      transcriptional regulation of the c-met gene. Cotransfection of various c-met
      promoter reporter vectors with p53 expression plasmids demonstrated that only
      wild-type p53 but not tumor-derived mutant forms of p53 resulted in a significant
      enhancement of c-met promoter activity. Functional assays revealed that the p53
      responsive element in the c-met promoter region is located at position -278 to 
      216 and confers p53 responsiveness not only in the context of the c-met promoter
      but also in the context of a heterologous promoter. Electrophoretic mobility
      shift assays using purified recombinant p53 protein showed that the p53 binding
      element identified within the c-met promoter specifically binds to p53 protein.
      Induction of p53 by UV irradiation in RKO cells that express wild-type p53
      increased the level of the endogenous c-met gene product and p21(WAF1/CIP1), a
      known target of p53 regulation. On the other hand, in RKO cells in which the
      function of p53 is impaired either by stable transfection of a dominant negative
      form of p53 or by HPV-E6 viral protein, no induction of the endogenous c-met gene
      or p21(WAF1/CIP1) was noted by UV irradiation. These results suggest that the c
      met gene is also a target of p53 gene regulation.

PMID- 9920904
TI  - Control of G2/M transition in Xenopus by a member of the p21-activated kinase
      (PAK) family: a link between protein kinase A and PAK signaling pathways?
AB  - X-PAKs are involved in negative control of the process of oocyte maturation in
      Xenopus (). In the present study, we define more precisely the events targetted
      by the kinase in the inhibition of the G2/M transition. We show that
      microinjection of recombinant X-PAK1-Cter active kinase into progesterone-treated
      oocytes prevents c-Mos accumulation and activation of both MAPK and maturation
      promoting factor (MPF). In conditions permissive for MAPK activation, MPF
      activation still fails. We demonstrate that a constitutive truncated version of X
      PAK1 (X-PAK1-Cter) does not prevent the association of cyclin B with p34(cdc2)
      but rather prevents the activation of the inactive complexes present in the
      oocyte. Proteins participating in the MPF amplification loop, including the Cdc25
      activating Polo-like kinase are all blocked. Indeed, using active MPF, the
      amplification loop is not turned on in the presence of X-PAK1. Our results
      indicate that X-PAK and protein kinase A targets in the control of oocyte
      maturation are similar and furthermore that this negative regulation is not
      restricted to meiosis, because we demonstrate that G2/M progression is also
      prevented in Xenopus cycling extracts in the presence of active X-PAK1.

PMID- 9920905
TI  - Molecular determinants of oligomer formation and complement fixation in mannose
      binding proteins.
AB  - Rat serum mannose-binding protein (MBP-A) functions as part of the innate immune
      system by targetting complement toward potentially pathogenic microorganisms. In
      order to examine the molecular basis for complement activation, rat MBP-A has
      been overproduced in Chinese hamster ovary cells. Recombinant protein is post
      translationally modified in the same way as the native lectin. Hydrodynamic
      studies indicate that MBP-A consists predominantly of covalent oligomers
      containing one to four copies of a subunit that comprises a trimer of
      polypeptides. These oligomers are non-interconverting and do not assemble into
      higher order structures at concentrations in excess of those normally found in
      serum. Disulfide bonds formed between cysteine residues at the N-terminal end of
      the collagen-like domain link polypeptides to form covalent oligomers. Analysis
      of wild-type MBP-A and MBP-A containing the substitution Cys6 --> Ser suggests
      that polypeptides within each trimeric structural unit are mostly linked by
      disulfide bonds between cysteine residues at positions 13 and 18 arranged in an
      asymmetrical configuration. Disulfide bonds involving Cys6 connect polypeptides
      within separate trimers. Analysis of chimeras between MBP-A and rat liver MBP
      (MBP-C) indicates that residues within the N-terminal region of the collagenous
      domain and the cysteine-rich domain of MBP-A enable assembly of trimers into
      higher order oligomers. The activity of MBP-A in a hemolytic complement fixation
      assay using mannan-coated sheep erythrocytes was approximately 20-fold greater
      than the activity of MBP-C. Analysis of the MBP chimeras and isolated oligomers
      of MBP-A reveals that the larger oligomers are more efficient at complement
      activation. These data indicate that the overall complement fixing activity of
      MBP-A is a function of the individual molecular activities of oligomers and their
      relative abundance within the serum.

PMID- 9920906
TI  - Structural requirements for alpha-latrotoxin binding and alpha-latrotoxin
      stimulated secretion. A study with calcium-independent receptor of alpha
      latrotoxin (CIRL) deletion mutants.
AB  - Stimulation of neurotransmitter release by alpha-latrotoxin requires its binding
      to the calcium-independent receptor of alpha-latrotoxin (CIRL), an orphan
      neuronal G protein-coupled receptor. CIRL consists of two noncovalently bound
      subunits, p85, a heptahelical integral membrane protein, and p120, a large
      extracellular polypeptide with domains homologous to lectin, olfactomedin, mucin,
      the secretin receptor family, and a novel structural motif common for large
      orphan G protein-coupled receptors. The analysis of CIRL deletion mutants
      indicates that the high affinity alpha-latrotoxin-binding site is located within
      residues 467-891, which comprise the first transmembrane segment of p85 and the C
      terminal half of p120. The N-terminal lectin, olfactomedin, and mucin domains of
      p120 are not required for the interaction with alpha-latrotoxin. Soluble p120 and
      all its fragments, which include the 467-770 residues, bind alpha-latrotoxin with
      low affinity suggesting the importance of membrane-embedded p85 for the
      stabilization of the complex of the toxin with p120. Two COOH-terminal deletion
      mutants of CIRL, one with the truncated cytoplasmic domain and the other with
      only one transmembrane segment left of seven, supported both alpha-latrotoxin
      induced calcium uptake in HEK293 cells and alpha-latrotoxin-stimulated secretion
      when expressed in chromaffin cells, although with a different dose dependence
      than wild-type CIRL and its N-terminal deletion mutant. Thus the signaling
      domains of CIRL are not critically important for the stimulation of exocytosis in
      intact chromaffin cells by alpha-latrotoxin.

PMID- 9920907
TI  - Phosphatidylinositol 3-kinase translocates onto liver endoplasmic reticulum and
      may account for the inhibition of glucose-6-phosphatase during refeeding.
AB  - By using a rapid procedure of isolation of microsomes, we have shown that the
      liver glucose-6-phosphatase activity was lowered by about 30% (p < 0.001) after
      refeeding for 360 min rats previously unfed for 48 h, whereas the amount of
      glucose-6-phosphatase protein was not lowered during the same time. The amount of
      the regulatory subunit (p85) and the catalytic activity of phosphatidylinositol 3
      kinase (PI3K) were higher by a factor of 2.6 and 2.4, respectively (p < 0.01), in
      microsomes from refed as compared with fasted rats. This resulted from a
      translocation process because the total amount of p85 was the same in the whole
      liver homogenates from fasted and refed rats. The amount of insulin receptor
      substrate 1 (IRS1) was also higher by a factor of 2.6 in microsomes from refed
      rats (p < 0. 01). Microsome-bound IRS1 was only detected in p85
      immunoprecipitates. These results strongly suggest that an insulin-triggered
      mechanism of translocation of PI3K onto microsomes occurs in the liver of rats
      during refeeding. This process, via the lipid products of PI3K, which are potent
      inhibitors of glucose-6-phosphatase (Mithieux, G., Daniele, N., Payrastre, B.,
      and Zitoun, C. (1998) J. Biol. Chem. 273, 17-19), may account for the inhibition
      of the enzyme and participate to the inhibition of hepatic glucose production
      occurring in this situation.

PMID- 9920908
TI  - Efficient endocytosis of the cystic fibrosis transmembrane conductance regulator
      requires a tyrosine-based signal.
AB  - We previously demonstrated that the cystic fibrosis transmembrane conductance
      regulator (CFTR) is rapidly endocytosed in epithelial cells (Prince, L. S.,
      Workman, R. B., Jr., and Marchase, R. B. (1994) Proc. Natl. Acad. Sci. U. S. A.
      91, 5192-5196). To determine the structural features of CFTR required for
      endocytosis, we prepared chimeric molecules consisting of the amino-terminal
      (residues 2-78) and carboxyl-terminal tail regions (residues 1391-1476) of CFTR,
      each fused to the transmembrane and extracellular domains of the transferrin
      receptor. Functional analysis of the CFTR-(2-78) and CFTR-(1391-1476) indicated
      that both chimeras were rapidly internalized. Deletion of residues 1440-1476 had
      no effect on chimera internalization. Mutations of potential internalization
      signals in both cytoplasmic domains reveal that only one mutation inhibits
      internalization, Y1424A. Using a surface biotinylation reaction, we also examined
      internalization rates of wild type and mutant CFTRs expressed in COS-7 cells. We
      found that both wild type and A1440X CFTR were rapidly internalized, whereas the
      Y1424A CFTR mutant, like the chimeric protein, had approximately 40% reduced
      internalization activity. Deletions in the amino-terminal tail region of CFTR
      resulted in defective trafficking of CFTR out of the endoplasmic reticulum to the
      cell surface, suggesting that an intact amino terminus is critical for
      biosynthesis. In summary, our results suggest that both tail regions of CFTR are
      sufficient to promote rapid internalization of a reporter molecule and that
      tyrosine 1424 is required for efficient CFTR endocytosis.

PMID- 9920909
TI  - Calbrain, a novel two EF-hand calcium-binding protein that suppresses
      Ca2+/calmodulin-dependent protein kinase II activity in the brain.
AB  - A cDNA clone that encodes a novel Ca2+-binding protein was isolated from a human
      brain cDNA library. The gene for this clone, termed calbrain, encodes a 70-amino
      acid polypeptide with a predicted molecular mass of 8.06 kDa. The analysis of
      deduced amino acid sequence revealed that calbrain contains two putative EF-hand
      motifs that show significantly high homology to those of the calmodulin (CaM)
      family rather than two EF-hand protein families. By Northern hybridization
      analysis, an approximate 1.5-kilobase pair transcript of calbrain was detected
      exclusively in the brain, and in situ hybridization study revealed its abundant
      expression in the hippocampus, habenular area in the epithalamus, and in the
      cerebellum. A recombinant calbrain protein showed a Ca2+ binding capacity,
      suggesting the functional potency as a regulator of Ca2+-mediated cellular
      processes. Ca2+/calmodulin-dependent kinase II, the most abundant protein kinase
      in the hippocampus and strongly implicated in the basic neuronal functions, was
      used to evaluate the physiological roles of calbrain. Studies in vitro revealed
      that calbrain competitively inhibited CaM binding to Ca2+/calmodulin-dependent
      kinase II (Ki = 129 nM) and reduced its kinase activity and autophosphorylation.

PMID- 9920910
TI  - Identification of the adenine binding site of the human A1 adenosine receptor.
AB  - To provide new insights into ligand-A1 adenosine receptor (A1AR) interactions,
      site-directed mutagenesis was used to test the role of several residues in the
      first four transmembrane domains of the human A1AR. First, we replaced eight
      unique A1AR residues with amino acids present at corresponding transmembrane (TM)
      positions of A2AARs. We also tested the role of carboxamide amino acids in TMs 1
      4, and the roles of Val-87, Leu-88, and Thr-91 in TM3. Following conversion of
      Gly-14 in TM1 to Thr-14, the affinity for adenosine agonists increased 100-fold,
      and after Pro-25 in TM1 was converted to Leu-25, the affinity for agonists fell.
      After conversion of TM3 sites Thr-91 to Ala-91, and Gln-92 to Ala-92, the
      affinity for N6-substituted agonists was reduced, and binding of ligands without
      N6 substituents was eliminated. When Leu-88 was converted to Ala-88, the binding
      of ligands with N6 substituents was reduced to a greater extent than ligands
      without N6 substituents. Following conversion of Pro-86 to Phe-86, the affinity
      for N6-substituted agonists was lost, and the affinity for ligands without N6
      substitution was reduced. These observations strongly suggest that Thr-91 and Gln
      92 in TM3 interact with the adenosine adenine moiety, and Leu-88 and Pro-86 play
      roles in conferring specificity for A1AR selective compounds. Using computer
      modeling based on the structure of rhodopsin, a revised model of adenosine-A1AR
      interactions is proposed with the N6-adenine position oriented toward the top of
      TM3 and the ribose group interacting with the bottom half of TMs 3 and 7.

PMID- 9920911
TI  - T cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd
      associated photoreactive peptide derivative.
AB  - To elucidate the structural basis of T cell recognition of hapten-modified
      antigenic peptides, we studied the interaction of the T1 T cell antigen receptor
      (TCR) with its ligand, the H-2Kd-bound Plasmodium berghei circumsporozoite
      peptide 252-260 (SYIPSAEKI) containing photoreactive 4-azidobenzoic acid (ABA) on
      P. berghei circumsporozoite Lys259. The photoaffinity-labeled TCR residue(s) were
      mapped as Tyr48 and/or Tyr50 of complementary determining region 2beta
      (CDR2beta). Other TCR-ligand contacts were identified by mutational analysis.
      Molecular modeling, based on crystallographic coordinates of closely related TCR
      and major histocompatibility complex I molecules, indicated that ABA binds
      strongly and specifically in a cavity between CDR3alpha and CDR2beta. We conclude
      that TCR expressing selective Vbeta and CDR3alpha sequences form a binding domain
      between CDR3alpha and CDR2beta that can accommodate nonpeptidic moieties
      conjugated at the C-terminal portion of peptides binding to major
      histocompatibility complex (MHC) encoded proteins.

PMID- 9920913
TI  - The fidelity of DNA polymerase beta during distributive and processive DNA
      synthesis.
AB  - During base excision repair, DNA polymerase beta fills 1-6-nucleotide gaps
      processively, reflecting a contribution of both its 8- and 31-kDa domains to DNA
      binding. Here we report the fidelity of pol beta during synthesis to fill gaps of
      1, 5, 6, or >300 nucleotides. Error rates during distributive synthesis by
      recombinant rat and human polymerase (pol) beta with a 390-base gap are similar
      to each other and to previous values with pol beta purified from tissues. The
      base substitution fidelity of human pol beta when processively filling a 5
      nucleotide gap is similar to that with a 361-nucleotide gap, but "closely-spaced"
      substitutions are produced at a rate at least 60-fold higher than for
      distributive synthesis. Base substitution fidelity when filling a 1-nucleotide
      gap is higher than when filling a 5-nucleotide gap, suggesting a contribution of
      the 8-kDa domain to the dNTP binding pocket and/or a difference in base stacking
      or DNA structure imposed by pol beta. Nonetheless, 1-nucleotide gap filling is
      inaccurate, even generating complex substitution-addition errors. Finally, the
      single-base deletion error rate during processive synthesis to fill a 6
      nucleotide gap is indistinguishable from that of distributive synthesis to fill a
      390-nucleotide gap. Thus the mechanism of processivity by pol beta does not allow
      the enzyme to suppress template misalignments.

PMID- 9920912
TI  - Metaphyseal chondrodysplasia type Schmid mutations are predicted to occur in two
      distinct three-dimensional clusters within type X collagen NC1 domains that
      retain the ability to trimerize.
AB  - Metaphyseal chondrodysplasia type Schmid (MCDS) is caused by mutations in COL10A1
      that are clustered in the carboxyl-terminal non-collagenous (NC1) encoding
      domain. This domain is responsible for initiating trimerization of type X
      collagen during biosynthesis. We have built a molecular model of the NC1 domain
      trimer based on the crystal structure coordinates of the highly homologous
      trimeric domain of ACRP30 (adipocyte complement-related protein of 30 kDa or
      AdipoQ). Mapping of the MCDS mutations onto the structure reveals two specific
      clusters of residues as follows: one on the surface of the monomer which forms a
      tunnel through the center of the assembled trimer and the other on a patch
      exposed to solvent on the exterior surface of each monomeric unit within the
      assembled trimer. Biochemical studies on recombinant trimeric NC1 domain show
      that the trimer has an unusually high stability not exhibited by the closely
      related ACRP30. The high thermal stability of the trimeric NC1 domain, in
      comparison with ACRP30, appears to be the result of a number of factors including
      the 17% greater total buried solvent-accessible surface and the increased numbers
      of hydrophobic contacts formed upon trimerization. The 27 amino acid sequence
      present at the amino terminus of the NC1 domain, which has no counterpart in
      ACRP30, also contributes to the stability of the trimer. We have also shown that
      NC1 domains containing the MCDS mutations Y598D and S600P retain the ability to
      homotrimerize and heterotrimerize with wild type NC1 domain, although the
      trimeric complexes formed are less stable than those of the wild type molecule.
      These studies suggest strongly that the predominant mechanism causing MCDS
      involves a dominant interference of mutant chains on wild type chain assembly.

PMID- 9920914
TI  - Interaction of arylsulfatase A with UDP-N-acetylglucosamine:Lysosomal enzyme-N
      acetylglucosamine-1-phosphotransferase.
AB  - The critical step in lysosomal targeting of soluble lysosomal enzymes is the
      recognition by an UDP-N-acetylglucosamine:lysosomal enzyme-N-acetylglucosamine-1
      phosphotransferase. The structure of the determinant common to all lysosomal
      enzymes for proper recognition by the phosphotransferase is not completely
      understood. Our current knowledge is largely based on the introduction of
      targeted amino acid substitutions into lysosomal enzymes and analysis of their
      effects on phosphotransferase recognition. We have investigated the effect of
      eight anti-arylsulfatase A monoclonal antibodies on the interaction of
      arylsulfatase A with the lysosomal enzyme phosphotransferase in vitro. We also
      show that a lysine-rich surface area of arylsulfatases A and B is essential for
      proper recognition by the phosphotransferase. Monoclonal antibodies bind to at
      least six different epitopes at different locations on the surface of
      arylsulfatase A. All antibodies bind outside the lysine-rich recognition area,
      but nevertheless Fab fragments of these antibodies prevent interaction of
      arylsulfatase A with the phosphotransferase. Our data support a model in which
      binding of arylsulfatase A to the phosphotransferase is not restricted to a
      limited surface area but involves the simultaneous recognition of large parts of
      arylsulfatase A.

PMID- 9920915
TI  - Structural analysis of human phospholipase D1.
AB  - Activation of phosphatidylcholine-specific phospholipase D (PLD) has been
      proposed to play roles in numerous cellular pathways including signal
      transduction and membrane vesicular trafficking. We previously reported the
      cloning of two mammalian genes, PLD1 and PLD2, that encode PLD activities. We
      additionally reported that PLD1 is activated in a synergistic manner by protein
      kinase c-alpha (PKC-alpha), ADP-ribosylation factor 1 (ARF1), and Rho family
      members. We describe here molecular analysis of PLD1 using a combination of
      domain deletion and mutagenesis. We show that the amino-terminal 325 amino acids
      are required for PKC-alpha activation of PLD1 but not for activation by ARF1 and
      RhoA. This region does not contain the sole PKC-alpha interaction site and
      additionally functions to inhibit basal PLD activity in vivo. Second, a region of
      sequence unique to PLD1 (as compared with other PLDs) known as the "loop" region
      had been proposed to serve as an effector regulatory region but is shown here
      only to mediate inhibition of PLD1. Finally, we show that modification of the
      amino terminus, but not of the carboxyl terminus, is compatible with PLD
      enzymatic function and propose a simple model for PLD activation.

PMID- 9920916
TI  - Kinesin takes one 8-nm step for each ATP that it hydrolyzes.
AB  - Conventional kinesin is a motor protein that moves stepwise along microtubules
      carrying membrane-bound organelles toward the periphery of cells. The steps are
      of amplitude 8.1 nm, the distance between adjacent tubulin binding sites, and are
      powered by the hydrolysis of ATP. We have asked: how many steps does kinesin take
      for each molecule of ATP that it hydrolyzes? To answer this question, the
      motility and ATP hydrolysis of recombinant, heterotetrameric and homodimeric
      conventional Drosophila kinesins adsorbed to 200-nm-diameter casein-coated silica
      beads were assayed under identical, single-molecule conditions. Division of the
      speed by the maximum microtubule-activated ATPase rate gave a stoichiometry of 1.
      08 +/- 0.09 steps for each ATP hydrolyzed at 1 mM ATP. Therefore, under low loads
      in which the drag force << 1 pN, coupling between the chemical and mechanical
      cycles of kinesin is tight, consistent with conventional power stroke models. Our
      results rule out models that require two or more ATPs/step, such as some thermal
      ratchet models, or that propose multiple steps powered by single ATPs.

PMID- 9920917
TI  - Smad1 recognition and activation by the ALK1 group of transforming growth factor
      beta family receptors.
AB  - Two structural elements, the L45 loop on the kinase domain of the transforming
      growth factor-beta (TGF-beta) family type I receptors and the L3 loop on the MH2
      domain of Smad proteins, determine the specificity of the interactions between
      these receptors and Smad proteins. The L45 sequence of the TGF-beta type I
      receptor (TbetaR-I) specifies Smad2 interaction, whereas the related L45 sequence
      of the bone morphogenetic protein (BMP) type I receptor (BMPR-I) specifies Smad1
      interactions. Here we report that members of a third receptor group, which
      includes ALK1 and ALK2 from vertebrates and Saxophone from Drosophila,
      specifically phosphorylate and activate Smad1 even though the L45 sequence of
      this group is very divergent from that of BMPR-I. We investigated the structural
      elements that determine the specific recognition of Smad1 by ALK1 and ALK2. In
      addition to the receptor L45 loop and the Smad1 L3 loop, the specificity of this
      recognition requires the alpha-helix 1 of Smad1. The alpha-helix 1 is a conserved
      structural element located in the vicinity of the L3 loop on the surface of the
      Smad MH2 domain. Thus, Smad1 recognizes two distinct groups of receptors, the
      BMPR-I group and the ALK1 group, through different L45 sequences on the receptor
      kinase domain and a differential use of two surface structures on the Smad1 MH2
      domain.

PMID- 9920918
TI  - An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia
      cells.
AB  - Exposure of mammalian cells to UV light causes initial changes in the cell
      membrane, induces phosphorylation and clustering of growth factor/cytokine
      receptors, and activates the Jun N-terminal kinase/stress-activated protein
      kinase (JNK/SAPK) signaling pathway leading to programmed cell death (apoptosis).
      In this study, we found that an early event in the cell membrane of myeloblastic
      leukemia (ML-1) cells was the vigorous activation of the voltage-gated K+ channel
      by UV irradiation. The strong enhancement by UV irradiation of K+ channel
      activity in the cell membrane subsequently activated the JNK/SAPK signaling
      pathway and resulted in myeloblastic leukemia cell apoptosis. Suppression of UV
      induced K+ channel activation with specific channel blockers prevented UV-induced
      apoptosis through inhibition of UV-induced activation of the proteins SEK (SPAK
      kinase) and JNK. However, suppression of K+ channel activity could not protect
      cells from etoposide-induced apoptosis, which bypasses the membrane event.
      Elimination of extracellular Ca2+ had no effect on the UV-induced and K+ channel
      mediated JNK/SAPK activation. Thus, we have identified a novel mechanism in which
      activation of K+ channels by UV-irradiation upstream of SEK and SAPK/JNK mediates
      UV-induced myeloblastic cell apoptosis.

PMID- 9920919
TI  - Solution structure of a retro-inverso peptide analogue mimicking the foot-and
      mouth disease virus major antigenic site. Structural basis for its antigenic
      cross-reactivity with the parent peptide.
AB  - The antigenic activity of a 19-mer peptide corresponding to the major antigenic
      region of foot-and-mouth disease virus and its retro-enantiomeric analogue was
      found to be completely abolished when they were tested in a biosensor system in
      trifluoroethanol. This suggests that the folding pattern, which is alpha-helix in
      trifluoroethanol (confirmed by CD measurement), does not correspond to the
      biologically relevant conformation(s) recognized by antibodies. The NMR
      structures of both peptides were thus determined in aqueous solution. These
      studies showed that the two peptides exhibit similar folding features,
      particularly in their C termini. This may explain in part the cross-reactive
      properties of the two peptides in aqueous solution. However, the retro-inverso
      analogue appears to be more rigid than the parent peptide and contains five
      atypical beta-turns. This feature may explain why retro-inverso foot-and-mouth
      disease virus peptides are often better recognized than the parent peptide by
      anti-virion antibodies.

PMID- 9920920
TI  - Identification of the single-stranded DNA binding surface of the transcriptional
      coactivator PC4 by NMR.
AB  - The C-terminal domain of the eukaryotic transcriptional cofactor PC4 (PC4CTD) is
      known to bind with nanomolar affinity to single-stranded (ss)DNA. Here, NMR is
      used to study DNA binding by this domain in more detail. Amide resonance shifts
      that were observed in a 1H15N-HSQC-monitored titration of 15N-labeled protein
      with the oligonucleotide dT18 indicate that binding of the nucleic acid occurs by
      means of two anti-parallel channels that were previously identified in the PC4CTD
      crystal structure. The beta-sheets and loops that make up these channels exhibit
      above average flexibility in the absence of ssDNA, which is reflected in higher
      values of T1rho, reduced heteronuclear nuclear Overhauser effects and faster
      deuterium exchange rates for the amides in this region. Upon ssDNA binding, this
      excess flexibility is significantly reduced. The binding of ssDNA by symmetry
      related channels reported here provides a structural rationale for the preference
      of PC4CTD for juxtaposed single-stranded regions (e.g. in heteroduplexes)
      observed in earlier work.

PMID- 9920921
TI  - A testis-specific androgen receptor coregulator that belongs to a novel family of
      nuclear proteins.
AB  - We have characterized a novel partner for androgen receptor (AR), termed ARIP3,
      that interacts with the DNA-binding domain/zinc finger region of AR and is
      predominantly expressed in the testis. Rat ARIP3 is a nuclear protein comprising
      572 amino acids. It modulates AR-dependent but not basal transcription,
      suggesting that ARIP3 acts as an AR transcriptional coregulator. Except for the C
      terminal AR-interacting domain, ARIP3 contains distinct regions that are also
      present in two recently described proteins, a protein inhibitor of activated
      Stat3 and an RNA helicase II-interacting protein (Gu/RH-II binding protein).
      Conserved structural features of these proteins indicate the existence of a gene
      family involved in the regulation of various transcription factors. Collectively,
      ARIP3 belongs to a novel nuclear protein family and is perhaps the first tissue
      specific coregulator of androgen receptor.

PMID- 9920922
TI  - Mismatch extension by Escherichia coli DNA polymerase III holoenzyme.
AB  - The in vitro fidelity of Escherichia coli DNA polymerase III holoenzyme (HE) is
      characterized by an unusual propensity for generating (-1)-frameshift mutations.
      Here we have examined the capability of HE isolated from both a wild-type and a
      proofreading-impaired mutD5 strain to polymerize from M13mp2 DNA primer-templates
      containing a terminal T(template).C mismatch. These substrates contained either
      an A or a G as the next (5') template base. The assay allows distinction between:
      (i) direct extension of the terminal C (producing a base substitution), (ii)
      exonucleolytic removal of the C, or (iii), for the G-containing template,
      extension after misalignment of the C on the next template G (producing a (-1)
      frameshift). On the A-containing substrate, both HEs did not extend the terminal
      C (<1%); instead, they exonucleolytically removed it (>99%). In contrast, on the
      G-containing substrate, the MutD5 HE yielded 61% (-1)-frameshifts and 6% base
      substitutions. The wild-type HE mostly excised the mispaired C from this
      substrate before extension (98%), but among the 2% mutants, (-1)-frameshifts
      exceeded base substitutions by 20 to 1. The preference of polymerase III HE for
      misalignment extension over direct mismatch extension provides a basis for
      explaining the in vitro (-1)-frameshift specificity of polymerase III HE.

PMID- 9920923
TI  - Regulation of connexin channels by pH. Direct action of the protonated form of
      taurine and other aminosulfonates.
AB  - Protonated aminosulfonate compounds directly inhibit connexin channel activity.
      This was demonstrated by pH-dependent connexin channel activity in Good's pH
      buffers (MES (4-morpholineethanesulfonic acid)), HEPES, and TAPS (3-({[2-hydroxy
      1, 1-bis(hydroxymethyl)ethyl]amino]-1-propanesulfonic acid)) that have an
      aminosulfonate moiety in common and by the absence of pH-dependent channel
      activity in pH buffers without an aminosulfonate moiety (maleate, Tris, and
      bicarbonate). The pH-activity relation was shifted according to the pKa of each
      aminosulfonate pH buffer. At constant pH, increased aminosulfonate concentration
      inhibited channel activity. Taurine, a ubiquitous cytoplasmic aminosulfonic acid,
      had the same effect at physiological concentrations. These data raise the
      possibility that effects on connexin channel activity previously attributed to
      protonation of connexin may be mediated instead by protonation of cytoplasmic
      regulators, such as taurine. Modulation by aminosulfonates is specific for
      heteromeric connexin channels containing connexin-26; it does not occur
      significantly for homomeric connexin-32 channels. The identification of taurine
      as a cytoplasmic compound that directly interacts with and modulates connexin
      channel activity is likely to facilitate understanding of cellular modulation of
      connexin channels and lead to the development of reagents for use in structure
      function studies of connexin protein.

PMID- 9920924
TI  - Direct high affinity modulation of connexin channel activity by cyclic
      nucleotides.
AB  - Connexin channels mediate molecular communication between cells. However,
      positive identification of biological ligands that directly and noncovalently
      modulate their activity has been elusive. This study demonstrates a high affinity
      inhibition of connexin channels by the purine cyclic monophosphates cAMP and
      cGMP. Purified homomeric connexin-32 and heteromeric connexin-32/connexin-26
      channels were inhibited by exposure to nanomolar levels of the nucleotides prior
      to incorporation into membranes. Access to the site of action, or affinity for
      the nucleotides, was greatly reduced following incorporation of the connexin
      channels into membranes, where inhibition required millimolar concentrations of
      the nucleotides. The high affinity inhibition did not occur with similar
      concentrations of AMP, ADP, ATP, cTMP, or cCMP. This is the first report of a
      direct ligand effect on connexin channel function. The high affinity and
      specificity of the inhibition suggest a biological role in control of connexin
      channels and also may lead to the application of affinity reagents to study of
      connexin channel structure-function.

PMID- 9920925
TI  - The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif.
AB  - Ephrin B proteins function as ligands for B class Eph receptor tyrosine kinases
      and are postulated to possess an intrinsic signaling function. The sequence at
      the carboxyl terminus of B-type ephrins contains a putative PDZ binding site,
      providing a possible mechanism through which transmembrane ephrins might interact
      with cytoplasmic proteins. To test this notion, a day 10.5 mouse embryonic
      expression library was screened with a biotinylated peptide corresponding to the
      carboxyl terminus of ephrin B3. Three of the positive cDNAs encoded polypeptides
      with multiple PDZ domains, representing fragments of the molecule GRIP, the
      protein syntenin, and PHIP, a novel PDZ domain-containing protein related to
      Caenorhabditis elegans PAR-3. In addition, the binding specificities of PDZ
      domains previously predicted by an oriented library approach (Songyang, Z.,
      Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A.,
      Chan, A. C., Anderson, J. M., and Cantley, L. C. (1997) Science 275, 73-77)
      identified the tyrosine phosphatase FAP-1 as a potential binding partner for B
      ephrins. In vitro studies demonstrated that the fifth PDZ domain of FAP-1 and
      full-length syntenin bound ephrin B1 via the carboxyl-terminal motif. Lastly,
      syntenin and ephrin B1 could be co-immunoprecipitated from transfected COS-1
      cells, suggesting that PDZ domain binding of B ephrins can occur in cells. These
      results indicate that the carboxyl-terminal motif of B ephrins provides a binding
      site for specific PDZ domain-containing proteins, which might localize the
      transmembrane ligands for interactions with Eph receptors or participate in
      signaling within ephrin B-expressing cells.

PMID- 9920926
TI  - Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via
      involvement of caspase-1, leading to apoptosis of photoreceptor cells.
AB  - The mechanisms of photoreceptor cell death via apoptosis, in retinal dystrophies,
      are largely not understood. In the present report we show that visible light
      exposure of mouse cultured 661W photoreceptor cells at 4.5 milliwatt/cm2 caused a
      significant increase in oxidative damage of 661W cells, leading to apoptosis of
      these cells. These cells show constitutive expression of nuclear factor-kappaB
      (NF-kappaB), and light exposure of photoreceptor cells results in lowering of NF
      kappaB levels in both the nuclear and cytosolic fractions in a time-dependent
      manner. Immunoblot analysis of IkappaBalpha and p50, and p65 (RelA) subunits of
      NF-kappaB, suggested that photo-oxidative stress results in their depletion.
      Immunocytochemical studies using antibody to RelA subunit of NF-kappaB further
      revealed the presence of this subunit constitutively both in the nucleus and
      cytoplasm of the 661W cells. Upon exposure to photo-oxidative stress, a depletion
      of the cytoplasmic and nuclear RelA subunit was observed. The depletion of NF
      kappaB appears to be mediated through involvement of caspase-1. Furthermore,
      transfection of these cells with a dominant negative mutant IkappaBalpha greatly
      enhanced the kinetics of down modulation of NF-kappaB, resulting in a faster
      photo-oxidative stress-induced apoptosis. Taken together, these studies show that
      the presence of NF-kappaB RelA subunit in the nucleus is essential for protection
      of photoreceptor cells against apoptosis mediated by an oxidative pathway.

PMID- 9920927
TI  - Rho-associated kinase of chicken gizzard smooth muscle.
AB  - Rho-associated kinase (Rho-kinase) from chicken gizzard smooth muscle was
      purified to apparent homogeneity (160 kDa on SDS-polyacrylamide gel
      electrophoresis) and identified as the ROKalpha isoform. Several substrates were
      phosphorylated. Rates with myosin phosphatase target subunit 1 (MYPT1), myosin,
      and the 20-kDa myosin light chain were higher than other substrates.
      Thiophosphorylation of MYPT1 inhibited myosin phosphatase activity.
      Phosphorylation of myosin at serine 19 increased actin-activated Mg+-ATPase
      activity, i.e. similar to myosin light chain kinase. Myosin phosphorylation was
      increased at higher ionic strengths, possibly by formation of 6 S myosin.
      Phosphorylation of the isolated light chain and myosin phosphatase was decreased
      by increasing ionic strength. Rho-kinase was stimulated 1.5-2-fold by guanosine
      5'-O-3-(thio)triphosphate.RhoA, whereas limited tryptic hydrolysis caused a 5-6
      fold activation, independent of RhoA. Several kinase inhibitors were screened and
      most effective were Y-27632, staurosporine, and H-89. Several lipids caused
      slight activation of Rho-kinase, but arachidonic acid (30-50 microM) induced a 5
      6-fold activation, independent of RhoA. These results suggest that Rho-kinase of
      smooth muscle may be involved in the contractile process via phosphorylation of
      MYPT1 and myosin. Activation by arachidonic acid presents a possible regulatory
      mechanism for Rho-kinase.

PMID- 9920928
TI  - E-selectin gene expression is induced synergistically with the coexistence of
      activated classic protein kinase C and signals elicited by interleukin-1beta but
      not tumor necrosis factor-alpha.
AB  - We have examined the effect of protein kinase C (PKC) on the expression of the E
      selectin and intercellular adhesion molecule-1 (ICAM-1) mRNAs in human umbilical
      vein endothelial cells. The lower classic PKC activity on pretreatment with
      phorbol ester (phorbol 12-myristate 13-acetate (PMA)) for 24 h markedly decreased
      IL-1beta-induced E-selectin mRNA expression in the presence of fetal calf serum
      and basic fibroblast growth factor, although the induction of ICAM-1 mRNA
      expression was only influenced a little by the PKC down-regulation. On the other
      hand, tumor necrosis factor-alpha (TNFalpha)-induced gene expression of these
      adhesion molecules was unaffected by such PKC modulation. The intracellular
      signals generated by interleukin (IL)-1beta and TNFalpha themselves are not
      mediated through classic PKC activation, because the response to neither
      stimulant was inhibited by the PKC down-regulation in the absence of fetal calf
      serum and basic fibroblast growth factor. Simultaneous treatment with IL-1beta
      and PMA synergistically induced E-selectin gene expression but not when TNFalpha
      was substituted for IL-1beta. ICAM-1 mRNA expression was only additively induced
      on the cotreatment. The synergistic effect on E-selectin mRNA induction was
      independent of de novo protein synthesis and mediated by elevated transcriptional
      activity. Promoter analysis of E-selectin indicated that the NF-ELAM1/activating
      transcription factor element is critical for the synergistic effect of the
      cotreatment with IL-1beta and PMA.

PMID- 9920929
TI  - Protein kinase calpha regulates human monocyte O-2 production and low density
      lipoprotein lipid oxidation.
AB  - Our previous studies have shown that human native low density lipoprotein (LDL)
      can be oxidized by activated human monocytes. In this process, both activation of
      protein kinase C (PKC) and induction of superoxide anion (O-2) production are
      required. PKC is a family of isoenzymes, and the functional roles of individual
      PKC isoenzymes are believed to differ based on subcellular location and distinct
      responses to regulatory signals. We have shown that the PKC isoenzyme that is
      required for both monocyte O-2 production and oxidation of LDL is a member of the
      conventional PKC group of PKC isoenzymes (Li, Q., and Cathcart, M. K. (1994) J.
      Biol. Chem. 269, 17508-17515). The conventional PKC group includes PKCalpha,
      PKCbetaI, PKCbetaII, and PKCgamma. With the exception of PKCgamma, each of these
      isoenzymes was detected in human monocytes. In these studies, we investigated the
      requirement for select PKC isoenzymes in the process of monocyte-mediated LDL
      lipid oxidation. Our data indicate that PKC activity was rapidly induced upon
      monocyte activation with the majority of the activity residing in the
      membrane/particulate fraction. This enhanced PKC activity was sustained for up to
      24 h after activation. PKCalpha, PKCbetaI, and PKCbetaII protein levels were
      induced upon monocyte activation, and PKCalpha and PKCbetaII substantially
      shifted their location from the cytosol to the particulate/membrane fraction. To
      distinguish between these isoenzymes for regulating monocyte O-2 production and
      LDL oxidation, PKCalpha or PKCbeta isoenzyme-specific antisense oligonucleotides
      were used to selectively suppress isoenzyme expression. We found that suppression
      of PKCalpha expression inhibited both monocyte-mediated O-2 production and LDL
      lipid oxidation by activated human monocytes. In contrast, inhibition of PKCbeta
      expression (including both PKCbetaI and PKCbetaII) did not affect O-2 production
      or LDL lipid oxidation. Further studies demonstrated that the respiratory burst
      oxidase responsible for O-2 production remained functionally intact in monocytes
      with depressed levels of PKCalpha because O-2 production could be restored by
      treating the monocytes with arachidonic acid. Taken together, our data reveal
      that PKCalpha, and not PKCbetaI or PKCbetaII, is the predominant isoenzyme
      required for O-2 production and maximal oxidation of LDL by activated human
      monocytes.

PMID- 9920931
TI  - Ornithine decarboxylase gene deletion mutants of Leishmania donovani.
AB  - A knockout strain of Leishmania donovani lacking both ornithine decarboxylase
      (ODC) alleles has been created by targeted gene replacement. Growth of Deltaodc
      cells in polyamine-deficient medium resulted in a rapid and profound depletion of
      cellular putrescine pools, although levels of spermidine were relatively
      unaffected. Concentrations of trypanothione, a spermidine conjugate, were also
      reduced, whereas glutathione concentrations were augmented. The Deltaodc L.
      donovani exhibited an auxotrophy for polyamines that could be circumvented by the
      addition of the naturally occurring polyamines, putrescine or spermidine, to the
      culture medium. Whereas putrescine supplementation restored intracellular pools
      of both putrescine and spermidine, exogenous spermidine was not converted back to
      putrescine, indicating that spermidine alone is sufficient to meet the polyamine
      requirement, and that L. donovani does not express the enzymatic machinery for
      polyamine degradation. The lack of a polyamine catabolic pathway in intact
      parasites was confirmed radiometrically. In addition, the Deltaodc strain could
      grow in medium supplemented with either 1,3-diaminopropane or 1, 5-diaminopentane
      (cadaverine), but polyamine auxotrophy could not be overcome by other aliphatic
      diamines or spermine. These data establish genetically that ODC is an essential
      gene in L. donovani, define the polyamine requirements of the parasite, and
      reveal the absence of a polyamine-degradative pathway.

PMID- 9920930
TI  - C3 toxin activates the stress signaling pathways, JNK and p38, but antagonizes
      the activation of AP-1 in rat-1 cells.
AB  - Lysophosphatidic acid (LPA) stimulates the c-Fos serum response element (SRE) by
      activating two distinct signal pathways regulated by the small GTPases, Ras and
      RhoA. Ras activates the ERK cascade leading to phosphorylation of the
      transcription factors Elk-1 and Sap1a at the Ets/TCF site. RhoA regulates an
      undefined pathway required for the activation of the SRF/CArG site. Here we have
      examined the role of the Ras and RhoA pathways in activation of the SRE and c-Fos
      expression in Rat-1 cells. Pertussis toxin and PD98059 strongly inhibited LPA
      stimulated c-Fos expression and activation of a SRE:Luc reporter. C3 toxin
      completely inhibited RhoA function, partially inhibited SRE:Luc activity, but had
      no effect on LPA-stimulated c-Fos expression. Thus, in a physiological context
      the Ras-Raf-MEK-ERK pathway, but not RhoA, is required for LPA-stimulated c-Fos
      expression in Rat-1 cells. C3 toxin stimulated the stress-activated protein
      kinases JNK and p38 and potentiated c-Jun expression and phosphorylation; these
      properties were shared by another cellular stress agonist the protein kinase C
      inhibitor Ro-31-8220. However, C3 toxin alone or in combination with growth
      factors did not stimulate AP-1:Luc activity and actually antagonized the
      synergistic activation of AP-1:Luc observed in response to co-stimulation with
      growth factors and Ro-31-8220. These data indicate that C3 toxin is a cellular
      stress which antagonizes activation of AP-1 at a point downstream of stress
      activated kinase activation or immediate-early gene induction.

PMID- 9920932
TI  - Synthetic peptides derived from the variable regions of an anti-CD4 monoclonal
      antibody bind to CD4 and inhibit HIV-1 promoter activation in virus-infected
      cells.
AB  - The monoclonal antibody (mAb) ST40, specific for the immunoglobulin
      complementarity-determining region (CDR) 3-like loop in domain 1 of the CD4
      molecule, inhibits human immunodeficiency virus type 1 (HIV-1) promoter activity
      and viral transcription in HIV-infected cells. To design synthetic peptides from
      the ST40 paratope that could mimic these biological properties, a set of 220
      overlapping 12-mer peptides frameshifted by one residue, corresponding to the
      deduced ST40 amino acid sequence, was synthesized by the Spot method and tested
      for binding to recombinant soluble CD4 antigen. Several peptides that included in
      their sequences amino acids from the CDRs of the antibody and framework residues
      flanking the CDRs were found to bind soluble CD4. Eleven paratope-derived
      peptides (termed CM1-CM11) were synthesized in a cyclic and soluble form. All the
      synthetic peptides showed CD4 binding capacity with affinities ranging from 1.6
      to 86.4 nM. Moreover, peptides CM2, CM6, CM7, CM9, and CM11 were able to bind a
      cyclic peptide corresponding to the CDR3-like loop in domain 1 of CD4 (amino
      acids 81-92 of CD4). Peptide CM9 from the light chain variable region of mAb ST40
      and, to a lesser extent, peptides CM2 and CM11 were able to inhibit HIV-1
      promoter long terminal repeat-driven beta-galactosidase gene expression in the
      HeLa P4 HIV-1 long terminal repeat beta-galactosidase indicator cell line
      infected with HIV-1. The binding of mAb ST40 to CD4 was also efficiently
      displaced by peptides CM2, CM9, and CM11. Our results indicate that the
      information gained from a systematic exploration of the antigen binding capacity
      of synthetic peptides from immunoglobulin variable sequences can lead to the
      identification of bioactive paratope-derived peptides of potential
      pharmacological interest.

PMID- 9920933
TI  - The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus
      activated co-chaperone that modulates heat shock protein 70 activity.
AB  - P58(IPK), a member of the tetratricopeptide repeat and J-domain protein families,
      was first recognized for its ability to inhibit the double-stranded RNA-activated
      protein kinase, PKR. PKR is part of the interferon-induced host defense against
      viral infection, and down-regulates translation initiation via phosphorylation of
      eukaryotic initiation factor 2 on the alpha-subunit. P58(IPK) is activated in
      response to infection by influenza virus, and inhibits PKR through direct protein
      protein interaction. Previously, we demonstrated that the molecular chaperone
      heat shock protein 40 (hsp40) was a negative regulator of P58(IPK). We could now
      report that influenza virus activates the P58(IPK) pathway by promoting the
      dissociation of hsp40 from P58(IPK) during infection. We also found that the
      P58(IPK)-hsp40 association was disrupted during recovery from heat shock, which
      suggested a regulatory role for P58(IPK) in the absence of virus infection. The
      PKR pathway is even more complex as we show in this report that the molecular
      chaperone, hsp/Hsc70, was a component of a trimeric complex with hsp40 and
      P58(IPK). Moreover, like other J-domain proteins, P58(IPK) stimulated the ATPase
      activity of Hsc70. Taken together, our data suggest that P58(IPK) is a co
      chaperone, possibly directing hsp/Hsc70 to refold, and thus inhibit kinase
      function.

PMID- 9920935
TI  - Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST.
AB  - The protein tyrosine phosphatase PTP-PEST is a cytosolic enzyme that displays a
      remarkable degree of selectivity for tyrosine-phosphorylated p130(Cas) as a
      substrate, both in vitro and in intact cells. We have investigated the
      physiological role of PTP-PEST using Rat1 fibroblast-derived stable cell lines
      that we have engineered to overexpress PTP-PEST. These cell lines exhibit normal
      levels of tyrosine phosphorylation of the majority of proteins but have
      significantly lower levels of tyrosine phosphorylation of p130(Cas) than control
      cells. Initial cellular events occurring following integrin-mediated attachment
      to fibronectin (cell attachment and spreading) are essentially unchanged in cells
      overexpressing PTP-PEST; similarly, the extent and time course of mitogen
      activated protein kinase activation in response to integrin engagement is
      unchanged. In contrast, the reduced phosphorylation state of p130(Cas) is
      associated with a considerably reduced rate of cell migration and a failure of
      cells overexpressing PTP-PEST to accomplish the normally observed redistribution
      of p130(Cas) to the leading edge of migrating cells. Furthermore, cells
      overexpressing PTP-PEST demonstrate significantly reduced levels of association
      of p130(Cas) with the Crk adaptor protein. Our results suggest that one
      physiological role of PTP-PEST is to dephosphorylate p130(Cas), thereby
      controlling tyrosine phosphorylation-dependent signaling events downstream of
      p130(Cas) and regulating cell migration.

PMID- 9920934
TI  - The inactive form of a yeast casein kinase I suppresses the secretory defect of
      the sec12 mutant. Implication of negative regulation by the Hrr25 kinase in the
      vesicle budding from the endoplasmic reticulum.
AB  - Sec12p is the guanine nucleotide exchange factor of Sar1 GTPase and functions at
      the very upstream in the vesicle budding reactions from the endoplasmic reticulum
      (ER). We previously identified three yeast loci, RST1, RST2, and RST3, whose
      mutations suppressed the temperature-sensitive growth of the sec12-4 mutant
      (Nakano, A. (1996) J. Biochem. (Tokyo) 120, 642-646). In the present study, we
      cloned the wild-type RST2 gene by complementation of the cold-sensitive phenotype
      of the rst2-1 mutant. RST2 turned out to be identical to HRR25, a gene encoding a
      dual-specificity casein kinase I in yeast. The rst2-1 mutation, which is now
      renamed hrr25-2, was due to the T176I amino acid replacement in the kinase
      domain. This mutation remedied not only the temperature-sensitive growth but also
      the defect of ER-to-Golgi protein transport of sec12. Immunoprecipitation of the
      hemagglutinin-tagged Hrr25-2 protein and a subsequent protein kinase assay showed
      that the kinase activity of the mutant protein was markedly reduced. The
      overproduction of another kinase-minus mutant of Hrr25p (Hrr25p K38A) slightly
      suppressed the growth defect of sec12-4 as well. These observations suggest that
      the reduction of the kinase activity in the mutant protein is important for the
      suppression of sec12. We propose that Hrr25p negatively regulates the vesicle
      budding from the ER.

PMID- 9920936
TI  - Characterization of a novel ADP-ribosylation factor-like protein (yARL3) in
      Saccharomyces cerevisiae.
AB  - ADP-ribosylation factors (ARFs) are highly conserved, approximately 20-kDa
      guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase
      activity of cholera toxin and have an important role in vesicular transport.
      Several cDNAs for ARF-like proteins (ARLs) have been cloned from human,
      Drosophila, rat, and yeast, although the biological function(s) of ARLs is
      unknown. We have identified a yeast gene (yARL3) encoding a protein that is
      structurally related (>43% identical) to the mammalian ARF-like protein ARP.
      Biochemical studies of purified recombinant yARL3 protein revealed properties
      similar to those of ARF and ARL proteins, including the ability to bind and
      hydrolyze GTP. Like other ARLs, recombinant yARL3 did not stimulate cholera toxin
      catalyzed auto-ADP-ribosylation. Anti-yARL3 antibodies did not cross-react with
      yARFs or yARL1. yARL3 was not essential for cell viability, but disruption of
      yARL3 resulted in cold-sensitive cell growth. At the nonpermissive temperature,
      processing of alkaline phosphatase and carboxypeptidase Y in arl3 mutant was
      slowed. yARL3 might be required for protein transport from endoplasmic reticulum
      to Golgi or from Golgi to vacuole at nonpermissive temperatures. On subcellular
      fractionation, unlike its mammalian homologue ARP, yARL3 was detected in the
      soluble fraction but not in the plasma membrane. Indirect immunofluorescence
      analysis revealed that yARL3 when overexpressed was associated in part with the
      endoplasmic reticulum-nuclear envelope. Thus, the structural and functional
      characteristics of yARL3 indicate that it may have a unique role(s) in vesicular
      trafficking.

PMID- 9920937
TI  - Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for
      multiple inputs.
AB  - Lysophosphatidic acid (LPA) is a growth factor that exerts a number of well
      characterized biological actions on fibroblasts and other cells. In the present
      study, we investigated the possibility that LPA activates the transcription
      factor NF-kappaB. NF-kappaB is a target of cytokines, but its activation by other
      classes of agonists has raised considerable interest in the control of processes
      such as inflammation and wound healing through varied mechanisms. We find that
      LPA causes a marked activation of NF-kappaB in Swiss 3T3 fibroblasts as
      determined by the degradation of IkappaB-alpha in the cytosol and the emergence
      of kappaB binding activity in nuclear extracts. The EC50 for activation of NF
      kappaB is 1-5 microM, a range similar to that reported for reinitiation of DNA
      synthesis and activation of the serum response element. Activation of NF-kappaB
      is attenuated by pertussis toxin and inhibitors of protein kinase C, and it is
      completely blocked by the Ca2+ chelator BAPTA-AM. The combination of phorbol
      ester and thapsigargin promotes an activation comparable with that of LPA.
      Activation by LPA is additionally inhibited by tyrphostin A25 but not genistein
      or AG1478, indicating a selective utilization of protein-tyrosine kinases, and by
      certain antioxidants, implying a role for reactive oxygen species. The activation
      is also inhibited by tricyclodecan-9-yl-xanthogenate (D609), implying a
      requirement for hydrolysis of phosphatidylcholine. The data demonstrate the
      utilization of multiple pathways in the activation of NF-kappaB by LPA, not
      inconsistent with the relevance of several families of GTP-binding regulatory
      proteins.

PMID- 9920938
TI  - Molecular and biochemical characterization of lecithin retinol acyltransferase.
AB  - The enzyme responsible for conversion of all-trans-retinol into retinyl esters,
      the lecithin retinol acyltransferase (LRAT) has been characterized at the
      molecular level. The cDNA coding for this protein was cloned and its amino acid
      sequence deduced. LRAT is composed of a polypeptide of 230 amino acid residues
      with a calculated mass of 25.3 kDa. Tissue distribution analysis by Northern blot
      showed expression of a 5.0-kilobase transcript in the human retinal pigment
      epithelium as well as in other tissues that are known for their high LRAT
      activity and vitamin A processing. Affinity labeling experiments using specific
      compounds with high affinity for LRAT and monospecific polyclonal antibodies
      raised in rabbits against two peptide sequences for LRAT confirmed the molecular
      mass of LRAT as a 25-kDa protein. High performance liquid chromatography analysis
      of the reaction product formed by HEK-293 cells transfected with LRAT cDNA
      confirmed the ability of the transfected cells to convert [3H]all-trans-retinol
      into authentic [3H]all-trans-retinyl palmitate as chemically determined.

PMID- 9920939
TI  - S-adenosyl-L-homocysteine hydrolase regulates aldosterone-induced Na+ transport.
AB  - Aldosterone-induced Na+ reabsorption, in part, is regulated by a critical methyl
      esterification; however, the signal transduction pathway regulating this
      methylation remains unclear. The A6 cell line was used as a model epithelia to
      investigate regulation of aldosterone-induced Na+ transport by S-adenosyl-L
      homocysteine hydrolase (SAHHase), the only enzyme in vertebrates known to
      catabolize S-adenosyl-L-homocysteine (SAH), an end product inhibitor of methyl
      esterification. Sodium reabsorption was decreased within 2 h by 3-deazaadenosine,
      a competitive inhibitor of SAHHase, with a half inhibitory concentration between
      40 and 50 microM. Aldosterone increased SAH catabolism by activating SAHHase.
      Increased SAH catabolism was associated with a concomitant increase in S
      adenosylmethionine catabolism. Moreover, SAH decreased substrate methylation.
      Antisense oligonucleotide complementary to SAHHase mRNA decreased SAHHase
      activity and Na+ current by approximately 50%. Overexpression of SAHHase
      increased SAHHase activity and dependent substrate methyl esterification. Whereas
      basal Na+ current was not affected by overexpression of SAHHase, aldosterone
      induced current in SAHHase-overexpressing cells was significantly potentiated.
      These results demonstrate that aldosterone induction of SAHHase activity is
      necessary for a concomitant relief of the methylation reaction from end product
      inhibition by SAH and the subsequent increase in Na+ reabsorption. Thus,
      regulation of SAHHase activity is a control point for aldosterone signal
      transduction, but SAHHase is not an aldosterone-induced protein.

PMID- 9920940
TI  - 3'-Azido-3'-deoxythymidine-resistant mutants of DNA polymerase beta identified by
      in vivo selection.
AB  - We developed an in vivo selection to identify 3'-azido-3'-deoxythymidine (AZT)
      resistant mutants of rat DNA polymerase beta (pol beta). The selection utilizes
      pol beta's ability to substitute for Escherichia coli DNA polymerase I (pol I) in
      the SC18-12 strain, which lacks active pol I. pol beta allows SC18-12 cells to
      grow, but they depend on pol beta activity, so inhibition of pol beta by AZT
      kills them. We screened a library of randomly mutated pol beta cDNA for
      complementation of the pol I defect in the presence of AZT, and identified AZT
      resistant mutants. We purified two enzymes with nonconservative mutations in the
      palm domain of the polymerase. The substitutions D246V and R253M result in
      reductions in the steady-state catalytic efficiency (Kcat/Km) of AZT-TP
      incorporation. The efficiency of dTTP incorporation was unchanged for the D246V
      enzyme, indicating that the substantial decrease in AZT-TP incorporation is
      responsible for its drug resistance. The R253M enzyme exhibits significantly
      higher Km(dTTP) and Kcat(dTTP) values, implying that the incorporation reaction
      is altered. These are the first pol beta mutants demonstrated to exhibit AZT
      resistance in vitro. The locations of the Asp-246 and Arg-253 side chains
      indicate that substrate specificity is influenced by residues distant from the
      nucleotide-binding pocket.

PMID- 9920941
TI  - Pokeweed antiviral protein accesses ribosomes by binding to L3.
AB  - Pokeweed antiviral protein (PAP), a 29-kDa ribosome-inactivating protein,
      catalytically removes an adenine residue from the conserved alpha-sarcin loop of
      the large rRNA, thereby preventing the binding of eEF-2.GTP complex during
      protein elongation. Because the alpha-sarcin loop has been placed near the
      peptidyltransferase center in Escherichia coli ribosomes, we investigated the
      effects of alterations at the peptidyltransferase center on the activity of PAP.
      We demonstrate here that a chromosomal mutant of yeast, harboring the mak8-1
      allele of peptidyltransferase-linked ribosomal protein L3 (RPL3), is resistant to
      the cytostatic effects of PAP. Unlike wild-type yeast, ribosomes from mak8-1
      cells are not depurinated when PAP expression is induced in vivo, indicating that
      wild-type L3 is required for ribosome depurination. Co-immunoprecipitation
      studies show that PAP binds directly to L3 or Mak8-1p in vitro but does not
      physically interact with ribosome-associated Mak8-1p. L3 is required for PAP to
      bind to ribosomes and depurinate the 25 S rRNA, suggesting that it is located in
      close proximity to the alpha-sarcin loop. These results demonstrate for the first
      time that a ribosomal protein provides a receptor site for an ribosome
      inactivating protein and allows depurination of the target adenine.

PMID- 9920942
TI  - Expansion and deletion of triplet repeat sequences in Escherichia coli occur on
      the leading strand of DNA replication.
AB  - Expansions and deletions of triplet repeat sequences that cause human hereditary
      neurological diseases were previously suggested to be mediated by the formation
      of DNA hairpins on the lagging strand during replication. The replication
      properties of CTG.CAG, CGG.CCG, and TTC.GAA repeats were studied in Escherichia
      coli using an in vivo phagemid system as a model for continuous leading strand
      synthesis. The repeats were substantially deleted when the CTG, CGG, and GAA
      repeats were the templates for rolling circle replication from the f1 phage
      origin. The deletions may be mediated by hairpins formed by these repeat tracts.
      The distributions of the deletion products of the CTG.CAG and CGG.CCG tracts
      indicated that hairpins of discrete sizes mediate deletions during complementary
      strand synthesis. Deletions during rolling circle synthesis are caused by larger
      hairpins of specific sizes. Thus, most deletion products were of defined lengths,
      suggesting a preference for specific hairpin intermediates. Small expansions of
      the CTG.CAG and CGG.CCG repeats were also observed, presumably due to the
      formation of CTG and CGG hairpins on the nascent complementary strand. Since
      rolling circle replication has been established in vitro as a model for leading
      strand synthesis, we conclude that triplet repeat instability can also occur on
      the leading strand of DNA replication.

PMID- 9920944
TI  - Regulation of the transglutaminase I gene. Identification of DNA elements
      involved in its transcriptional control in tracheobronchial epithelial cells.
AB  - The transglutaminase I (TGase I) gene encodes an enzyme that catalyzes the cross
      linking of structural proteins involved in the formation of the cornified
      envelope during squamous cell differentiation. To identify DNA elements important
      for the transcriptional control of the TGase I gene, we analyzed the ability of a
      2.9-kilobase pair (kb) upstream regulatory region to control the expression of a
      reporter gene in vivo and in vitro. Transgenic mice bearing the pTG(-2.9kb)CAT
      construct exhibited the same pattern of tissue-specific expression of CAT as
      reported for TGase I. Deletion analysis in transiently transfected rabbit
      tracheal epithelial cells indicated that two sequences from bp -490 to -470 and
      from -54 to -37 are involved in the activation of TGase I transcription. Point
      mutation analysis and mobility shift assays showed that the sequence located
      between -54 and -37 is a functional Sp1-like transcription element. Sp1 and Sp3,
      but not Sp2, are part of nuclear protein complexes from differentiated RbTE cells
      binding to this site. The element TGATGTCA between bp -490 and -470 is contained
      in a larger 22-bp palindrome and resembles the consensus cAMP response element
      binding protein (CREB)/AP-1 element recognized by dimeric complexes of members of
      the CREB, ATF, Fos, and Jun families. Mutations in this sequence greatly reduced
      promoter activity. Supershift analysis identified CREB1, JunB, c-Fos, Fra-1, and
      c-Jun in protein complexes isolated from differentiated rabbit tracheal
      epithelial cells binding to this site. Our study shows that the Sp1- and CREB/AP
      1-like sites act in concert to stimulate transcription of the TGase I gene. The
      2.9-kb promoter region could guide expression of specific genes in the granular
      layer of the epidermis and could be useful in gene therapy.

PMID- 9920943
TI  - cDNA cloning, sequencing, and characterization of male and female rat liver
      aldehyde oxidase (rAOX1). Differences in redox status may distinguish male and
      female forms of hepatic APX.
AB  - Molecular characterization of male and female rat liver aldehyde oxidase is
      reported. As described for the mouse liver, male and female rat liver expressed
      kinetically distinct forms of aldehyde oxidase. Our data suggest that the two
      forms arise as a result of differences in redox state and are most simply
      explained by expression of a single gene encoding aldehyde oxidase in rats. In
      support of this argument we have sequenced cDNAs from male and female rat liver.
      We examined mRNA expression by Northern blot analysis with RNA from males and
      females, from several tissues, and following androgen induction. Purified rat
      liver enzyme from males or females revealed a single 150-kDa species consistent
      with cDNA sequence analysis. Both male and female forms were reactive to the same
      carboxyl-terminal directed antisera. Km(app) values obtained in crude extracts of
      male or female rat liver and post-benzamidine-purified aldehyde oxidase differed
      substantially from each other but could be interconverted by chemical reduction
      with dithiothreitol or oxidation with 4,4'-dithiodipyridine. Our data indicate
      that a single gene is most likely expressed in male or female rat liver and that
      the kinetic differences between male and female rat liver aldehyde oxidases are
      sensitive to redox manipulation.

PMID- 9920945
TI  - The maize mitochondrial cox2 gene has five promoters in two genomic regions,
      including a complex promoter consisting of seven overlapping units.
AB  - Plant mitochondrial genes are often transcribed into complex sets of RNAs,
      resulting from multiple initiation sites and processing steps. To elucidate the
      role of initiation in generating the more than 10 cox2 transcripts found in maize
      mitochondria, we surveyed sequences upstream of cox2 for active promoters.
      Because the cox2 coding region is immediately downstream of a 0.7-kb
      recombination repeat, cox2 is under the control of two different sets of
      potential expression signals. Using an in vitro transcription assay, we localized
      four promoters upstream of the coding region in the so-called master chromosome,
      and two promoters upstream of the coding region in the recombinant subgenome.
      Ribonuclease protection analysis of labeled primary transcripts confirmed that
      all but one of these promoters is active in vivo. Primer extension was used to
      identify the promoter sequences and initiation sites, which agree with the
      consensus established earlier for maize mitochondria. This study identified two
      unusual promoters, the core sequences of which were composed entirely of adenines
      and thymines, and one of which was a complex promoter consisting of seven
      overlapping units. Deletion mutagenesis of the complex promoter suggested that
      each of its units was recognized independently by RNA polymerase. While each
      active promoter fit the maize core consensus sequence YRTAT, not all such
      sequences surveyed supported initiation. We conclude that in vitro transcription
      is a powerful tool for locating mitochondrial promoters and that, in the case of
      cox2, promoter multiplicity contributes strongly to transcript complexity.

PMID- 9920946
TI  - High affinity insertion/deletion lesion binding by p53. Evidence for a role of
      the p53 central domain.
AB  - In addition to binding DNA in a sequence-specific manner, p53 can interact with
      nucleic acids in a sequence-independent manner. p53 can bind short single
      stranded DNA and double-stranded DNA containing nucleotide loops; these diverse
      associations may be critical for p53 signal transduction. In this study, we
      analyzed p53 binding to DNA fragments containing insertion/deletion mismatches
      (IDLs). p53 required an intact central domain and dimerization domain for high
      affinity complex formation with IDLs. In fact, the C terminus of p53 (amino acids
      293-393) was functionally replaceable with a foreign dimerization domain in IDL
      binding assays. From saturation binding studies we determined that the KD of p53
      binding to IDLs was 45 pM as compared with a KD of 31 pM for p53 binding to DNA
      fragments containing a consensus binding site. Consistent with these dissociation
      constants, p53-IDL complexes were dissociated with relatively low concentrations
      of competitor consensus site-containing DNA. Although p53 has a higher affinity
      for DNA with a consensus site as compared with IDLs, the relative number and
      availability of each form of DNA in a cell immediately after DNA damage may
      promote p53 interaction with DNA lesions. Understanding how the sequence-specific
      and nonspecific DNA binding activities of p53 are integrated will contribute to
      our knowledge of how signaling cascades are initiated after DNA damage.

PMID- 9920947
TI  - Role of lipid modifications in targeting proteins to detergent-resistant membrane
      rafts. Many raft proteins are acylated, while few are prenylated.
AB  - Sphingolipid and cholesterol-rich Triton X-100-insoluble membrane fragments
      (detergent-resistant membranes, DRMs) containing lipids in a state similar to the
      liquid-ordered phase can be isolated from mammalian cells, and probably exist as
      discrete domains or rafts in intact membranes. We postulated that proteins with a
      high affinity for such an ordered lipid environment might be targeted to rafts.
      Saturated acyl chains should prefer an extended conformation that would fit well
      in rafts. In contrast, prenyl groups, which are as hydrophobic as acyl chains but
      have a branched and bulky structure, should be excluded from rafts. Here, we
      showed that at least half of the proteins in Madin-Darby canine kidney cell DRMs
      (other than cytoskeletal contaminants) could be labeled with [3H]palmitate.
      Association of influenza hemagglutinin with DRMs required all three of its
      palmitoylated Cys residues. Prenylated proteins, detected by [3H]mevalonate
      labeling or by blotting for Rap1, Rab5, Gbeta, or Ras, were excluded from DRMs.
      Rab5 and H-Ras each contain more than one lipid group, showing that
      hydrophobicity alone does not target multiply lipid-modified proteins to DRMs.
      Partitioning of covalently linked saturated acyl chains into liquid-ordered phase
      domains is likely to be an important mechanism for targeting proteins to DRMs.

PMID- 9920948
TI  - A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion
      protein, in patients with rheumatoid arthritis receiving methotrexate.
AB  - BACKGROUND: Patients treated with methotrexate for rheumatoid arthritis often
      improve but continue to have active disease. This study was undertaken to
      determine whether the addition of etanercept, a soluble tumor necrosis factor
      receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide
      additional benefit to patients who had persistent rheumatoid arthritis despite
      receiving methotrexate. METHODS: In a 24-week, double-blind trial, we randomly
      assigned 89 patients with persistently active rheumatoid arthritis despite at
      least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week
      (or as low as 10 mg per week for patients unable to tolerate higher doses) to
      receive either etanercept (25 mg) or placebo subcutaneously twice weekly while
      continuing to receive methotrexate. The primary measure of clinical response was
      the American College of Rheumatology criteria for a 20 percent improvement in
      measures of disease activity (ACR 20) at 24 weeks. RESULTS: The addition of
      etanercept to methotrexate therapy resulted in rapid and sustained improvement.
      At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate
      and 27 percent of those receiving placebo plus methotrexate met the ACR 20
      criteria (P<0.001); 39 percent of the patients receiving etanercept plus
      methotrexate and 3 percent of those receiving placebo plus methotrexate met the
      ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving
      etanercept plus methotrexate had significantly better outcomes according to all
      measures of disease activity. The only adverse events associated with etanercept
      were mild injection-site reactions, and no patient withdrew from the study
      because of adverse events associated with etanercept. CONCLUSIONS: In patients
      with persistently active rheumatoid arthritis, the combination of etanercept and
      methotrexate was safe and well tolerated and provided significantly greater
      clinical benefit than methotrexate alone.

PMID- 9920949
TI  - Prevalence of various respiratory viruses in the middle ear during acute otitis
      media.
AB  - BACKGROUND: Vaccines against respiratory viruses may be able to reduce the
      frequency of acute otitis media. Although the role of respiratory viruses in the
      pathogenesis of acute otitis media is well established, the relative importance
      of various viruses is unknown. METHODS: We determined the prevalence of various
      respiratory viruses in the middle-ear fluid in 456 children (age, two months to
      seven years) with acute otitis media. At enrollment and after two to five days of
      antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were
      obtained for viral and bacterial cultures and the detection of viral antigens.
      The viral cause of the infections was also assessed by serologic studies of serum
      samples obtained during the acute illness and convalescence. RESULTS: A specific
      viral cause of the respiratory tract infections was identified in 186 of the 456
      children (41 percent). Respiratory syncytial virus was the most common virus
      identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of
      the 65 children (74 percent) infected by this virus (P< or =0.04 for the
      comparison with any other virus). Parainfluenza viruses (15 of 29 children [52
      percent]) and influenzaviruses (10 of 24 children [42 percent]) were detected in
      the middle-ear fluid significantly more often than enteroviruses (3 of 27
      children [11 percent]) or adenoviruses (1 of 23 children [4 percent]) (P< or
      =0.01 for all comparisons). CONCLUSION: Respiratory syncytial virus is the
      principal virus invading the middle ear during acute otitis media. An effective
      vaccine against upper respiratory tract infections caused by respiratory
      syncytial virus may reduce the incidence of acute otitis media in children.

PMID- 9920950
TI  - Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell
      lung cancer treated concurrently with cisplatin and etoposide.
AB  - BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small
      cell lung cancer), thoracic radiotherapy improves survival, but the best ways of
      integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily
      accelerated thoracic radiotherapy has potential advantages over once-daily
      radiotherapy. METHODS: We studied 417 patients with limited small-cell lung
      cancer. All the patients received four 21-day cycles of cisplatin plus etoposide.
      We randomly assigned these patients to receive a total of 45 Gy of concurrent
      thoracic radiotherapy, given either twice daily over a three-week period or once
      daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with
      the first cycle of chemotherapy significantly improved survival as compared with
      concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median
      follow-up of almost 8 years, the median survival was 19 months for the once-daily
      group and 23 months for the twice-daily group. The survival rates for patients
      receiving once-daily radiotherapy were 41 percent at two years and 16 percent at
      five years. For patients receiving twice-daily radiotherapy, the survival rates
      were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis
      was significantly more frequent with twice-daily thoracic radiotherapy, occurring
      in 27 percent of patients, as compared with 11 percent in the once-daily group
      (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of
      radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of
      the chemotherapy resulted in overall two- and five-year survival rates of 44
      percent and 23 percent, a considerable improvement in survival rates over
      previous results in patients with limited small-cell lung cancer.

PMID- 9920951
TI  - A controlled trial of exercise rehabilitation after heart transplantation.
AB  - BACKGROUND: In patients who have received a cardiac transplant, the denervated
      donor heart responds abnormally to exercise and exercise tolerance is reduced.
      The role of physical exercise in the treatment of patients who have undergone
      cardiac transplantation has not been determined. We assessed the effects of
      training on the capacity for exercise early after cardiac transplantation.
      METHODS: Twenty-seven patients who were discharged within two weeks after
      receiving a heart transplant were randomly assigned to participate in a six-month
      structured cardiac-rehabilitation program (exercise group, 14 patients) or to
      undergo unstructured therapy at home (control group, 13 patients). Each patient
      in the exercise group underwent an individualized program of muscular-strength
      and aerobic training under the guidance of a physical therapist, whereas control
      patients received no formal exercise training. Cardiopulmonary stress testing was
      performed at base line (within one month after heart transplantation) and six
      months later. RESULTS: As compared with the control group, the exercise group had
      significantly greater increases in peak oxygen consumption (mean increase, 4.4 ml
      per kilogram of body weight per minute [49 percent] vs. 1.9 ml per kilogram per
      minute [18 percent]; P=0.01) and workload (mean increase, 35 W [59 percent] vs.
      12 W [18 percent]; P=0.01) and a greater reduction in the ventilatory equivalent
      for carbon dioxide (mean decrease, 13 [20 percent] vs. 6 [11 percent]; P=0.02).
      The mean dose of prednisone, the number of patients taking antihypertensive
      medications, the average number of episodes of rejection and of infection during
      the study period, and weight gain did not differ significantly between the
      groups. CONCLUSIONS: When initiated early after cardiac transplantation, exercise
      training increases the capacity for physical work.

PMID- 9920952
TI  - Pure red-cell aplasia associated with clonal expansion of granular lymphocytes
      expressing killer-cell inhibitory receptors.

PMID- 9920953
TI  - Images in clinical medicine. Brown-Sequard syndrome.

PMID- 9920954
TI  - Do "America's Best Hospitals" perform better for acute myocardial infarction?
AB  - BACKGROUND: "America's Best Hospitals," an influential list published annually by
      U.S. News and World Report, assesses the quality of hospitals. It is not known
      whether patients admitted to hospitals ranked at the top in cardiology have lower
      short-term mortality from acute myocardial infarction than those admitted to
      other hospitals or whether differences in mortality are explained by differential
      use of recommended therapies. METHODS: Using data from the Cooperative
      Cardiovascular Project on 149,177 elderly Medicare beneficiaries with acute
      myocardial infarction in 1994 or 1995, we examined the care and outcomes of
      patients admitted to three types of hospitals: those ranked high in cardiology
      (top-ranked hospitals); hospitals not in the top rank that had on-site facilities
      for cardiac catheterization, coronary angioplasty, and bypass surgery (similarly
      equipped hospitals); and the remaining hospitals (non-similarly equipped
      hospitals). We compared 30-day mortality; the rates of use of aspirin, beta
      blockers, and reperfusion; and the relation of differences in rates of therapy to
      short-term mortality. RESULTS: Admission to a top-ranked hospital was associated
      with lower adjusted 30-day mortality (odds ratio, 0.87; 95 percent confidence
      interval, 0.76 to 1.00; P=0.05 for top-ranked hospitals vs. the others). Among
      patients without contraindications to therapy, top-ranked hospitals had
      significantly higher rates of use of aspirin (96.2 percent, as compared with 88.6
      percent for similarly equipped hospitals and 83.4 percent for non-similarly
      equipped hospitals; P<0.01) and beta-blockers (75.0 percent vs. 61.8 percent and
      58.7 percent, P<0.01), but lower rates of reperfusion therapy (61.0 percent vs.
      70.7 percent and 65.6 percent, P=0.03). The survival advantage associated with
      admission to top-ranked hospitals was less strong after we adjusted for factors
      including the use of aspirin and beta-blockers (odds ratio, 0.94; 95 percent
      confidence interval, 0.82 to 1.08; P=0.38). CONCLUSIONS: Admission to a hospital
      ranked high on the list of "America's Best Hospitals" was associated with lower
      30-day mortality among elderly patients with acute myocardial infarction. A
      substantial portion of the survival advantage may be associated with these
      hospitals' higher rates of use of aspirin and beta-blocker therapy.

PMID- 9920955
TI  - Effects of admission to a teaching hospital on the cost and quality of care for
      Medicare beneficiaries.
AB  - BACKGROUND AND METHODS: We studied the effects of admission to a teaching
      hospital on the cost and quality of care for patients covered by Medicare (age,
      65 years old or older). We used data from the National Long Term Care Survey and
      merged them with Medicare claims data. We selected the first hospitalization for
      hip fracture (802 patients), stroke (793), coronary heart disease (1007), or
      congestive heart failure (604) occurring between January 1, 1984 and December 31,
      1994, and calculated all Medicare payments for inpatient and outpatient care
      during the six-month period after admission. Survival was assessed through 1995.
      Hospitals were classified as major or minor teaching hospitals (with minor
      hospitals defined as those in which the number of residents per bed was less than
      the median number for all teaching hospitals) or as private nonprofit, government
      (i.e., public), or private for-profit hospitals. RESULTS: Medicare payments for
      the six-month period after hospitalization were highest for patients initially
      admitted to teaching hospitals for the treatment of hip fracture, stroke, or
      coronary heart disease and for patients initially admitted to for-profit
      hospitals for the treatment of congestive heart failure. As compared with
      payments to for-profit hospitals, payments to major teaching hospitals for hip
      fracture were significantly higher, payments to government hospitals for coronary
      heart disease were lower, and payments to government and nonprofit hospitals for
      congestive heart failure were lower. After adjustment for patients'
      characteristics and social subsidies, major teaching hospitals had the lowest
      mortality rates (hazard ratio for death, 0.75, as compared with for-profit
      hospitals; 95 percent confidence interval, 0.62 to 0.91). For individual
      conditions, the only significant survival advantage associated with admission to
      major teaching hospitals was for hip fractures (hazard ratio, 0.54, as compared
      with for-profit hospitals; 95 percent confidence interval, 0.37 to 0.79).
      CONCLUSIONS: Although admission to a major teaching hospital may be associated
      with increased costs to the Medicare program, overall survival for patients with
      the common conditions we studied was better at these hospitals, especially for
      patients with hip fractures.

PMID- 9920957
TI  - Hospitals, heal yourselves.

PMID- 9920958
TI  - Anticytokine therapy--a new era in the treatment of rheumatoid arthritis?

PMID- 9920959
TI  - Respiratory viruses in acute otitis media.

PMID- 9920960
TI  - Does a low level of expression of HLA molecules engender autoimmunity?

PMID- 9920962
TI  - [The transferrin receptor: its role in iron metabolism and its diagnosis
      utility].
AB  - Transferrin receptor is a key protein for the cellular uptake of transferrin
      iron. The highest number of transferrin receptors is on the surface of
      erythroblasts. The released iron is used for hemoglobinosynthesis. Regulation
      occurs at mRNA level depending on the intracellular iron concentration. The
      synthesis of ferritin and transferrin receptor are regulated in an opposite
      manner. Serum transferrin receptor is a truncated monomeric form of the cellular
      receptor. Most of the circulating receptors come from erythroid marrow
      precursors. Its level mirrors the total tissue receptor mass, it depends on the
      rate of erythropoiesis and on the iron status. Serum transferrin receptor is
      easily measured by Elisa methods but the lack of standardization triggers large
      differences in the results. Unlike ferritin, the concentration of serum
      transferrin receptors is unaffected in inflammatory diseases, infections,
      malignancies or cytolysis. In these conditions its measurement is particularly
      valuable for assessing an associated iron deficiency. It is a very useful tool
      for the diagnosis of different causes of anemia. In chronic renal failure serum
      transferrin receptor can predict whether patients will respond to rHu EPO
      therapy.

PMID- 9920963
TI  - [Human herpesvirus 8 (HHV8). II. Pathogenic role and sensitivity to antiviral
      drugs].
AB  - Human herpesvirus 8 (HHV8) has been found to be associated with three different
      diseases observed in Aids patients: Kaposi's sarcoma, primary effusion lymphoma,
      which is a rare type of non-Hodgkin lymphomas affecting the body cavities, and
      multicentric Castleman's disease. The role of this new herpesvirus and other
      lymphoid proliferations, like angioimmunoblastic lymphadenopathy or multiple
      myeloma, is much debatable. To date, there are several evidences for a direct
      role of this virus in the occurrence of the Kaposi's sarcoma, although the
      hypothesis of a passenger virus hypothesis cannot be totally excluded. In vitro,
      HHV8 is sensitive to some anti-herpesvirus drugs like foscarnet, cidofovir and
      adefovir, but the indications of these therapies in the prevention or the
      treatment of the Kaposi's sarcoma have not been documented so far.

PMID- 9920964
TI  - [Bartonellosis. II. Other Bartonella responsible for human diseases].
AB  - In addition to Bartonella henselae, five other Bartonella species were involved
      in human pathology. As for B. henselae, ectoparasites seem to be responsible for
      the transmission of most or all these bacterial species. B. bacilliformis is
      responsible for Carrion's disease that occurs in some valleys of Colombia,
      Ecuador and Peru. This disease is transmitted by biting of infected sandflies.
      The bacterial reservoir is constituted by humans only. That disease occurs either
      as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as
      benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of
      the bacterium exist. Trench fever was described during the First World War. This
      non-lethal disease is constituted of recurrent febrile attacks associated
      particularly with osseous pains. The causative agent of the disease is B.
      quintana, transmitted by the body louse. Humans seem to be the reservoir of that
      bacterium. In some patients, B. quintana can be responsible for endocarditis,
      bacillary angiomatosis and chronic or recurrent bacteremia. Other human
      infections due to Bartonella sp. have been described: B. vinsonii, isolated from
      blood of small rodents, and B. elizabethae, the reservoir of which is currently
      unknown, can be responsible for endocardites. B. clarridgeiae (isolated from
      blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat
      scratch disease. All these bartonelloses are diagnosed by non-standard blood
      culture or by in vitro DNA amplification or by serological testing. Their
      treatment requires tetracyclines or chloramphenicol or macrolides.

PMID- 9920965
TI  - [Molecular genetics of the remethylation of homocysteine].
AB  - In plasma of mothers with a child affected with a neural tube defect plasma
      homocysteine is often elevated, and attributed to a reduced folate-dependent
      homocysteine remethylation. There is strong evidence that folic acid prevents
      fasting moderate hyperhomocysteinemia. The pathophysiology of neural tube defect
      and interactions between genetic and nutritional factors that determine plasma
      homocysteine levels remain poorly understood. Investigations on genetic causes of
      moderate hyperhomocysteinemia are in progress. This mini-review focuses on
      molecular genetic knowledge of folate-dependent homocysteine remethylation in
      neural tube defect.

PMID- 9920966
TI  - [Prospects for gene therapy in hematology].
AB  - Gene transfer in hematopoietic cells is intended to treat patients with malignant
      disease and inherited monogenic (hematological, immunological, and metabolic)
      disorders. Hematopoietic progenitor or stem cells are a favoured target for gene
      therapy because these cells are easily withdrawn from the patient, expanded and
      genetically modified ex vivo and then reinjected into the organism. Retroviral
      vectors allow an efficient transfer of the genes of interest. Transduction of
      stem cells leads to a stable expression of the transgene for long periods of
      time. However, we are at the beginning of this new therapeutic application, the
      technique was being already successful in very few cases. Problems to be solved
      are mainly in the understanding of the physiology of the hematopoietic stem cell
      and in the improvement of technical qualities of the vectors for a targeted gene
      transfer in vivo.

PMID- 9920967
TI  - [Lipid peroxidation, morphological stress pattern and nuclear maturity of
      spermatozoon].
AB  - Malondialdehyde, a stable lipid peroxidation product of polyunsaturated fatty
      acids, was assessed in sperm and seminal plasma of 21 patients to test a
      potential link between this compound and, the percentage of spermatozoon
      exhibiting a morphological stress pattern, and the results of the nuclear
      maturity test. An analysis by the Spearman rank correlation shows a statistically
      significant positive correlation between the sperm malondialdehyde levels and the
      percentage of spermatozoon with morphological stress pattern (r = 0.505, p =
      0.024). No correlation was found between the sperm malondialdehyde concentrations
      and the results of nuclear maturity test. The result of this work shows that
      spontaneous stress pattern seems to be linked, in part, to an excessive lipid
      peroxidation of the spermatozoon membrane. On the other hand, it seems that
      malondialdehyde have no effect on the chromatin maturity. According to the
      deleterious effects of lipid peroxidation on spermatozoon, the determination of
      both percentage of stress pattern and sperm malondialdehyde levels seems to
      provide useful information on the fertility status of patients.

PMID- 9920968
TI  - [Bibliographic analysis of the use of laboratory blood parameters for the
      prognosis of primary lung cancer].
AB  - In the daily clinical practice, serum calcium, albumin, and cyfra 21-1, are the
      only laboratory parameters officially recommended for the prognostic evaluation
      of primary lung cancer patients by the American, European or French
      respiratory/thoracic societies (and only in non-small cell lung cancer). The
      present review of the biomedical literature suggests that serum calcium for non
      operable non-small cell lung cancer, serum orosomucoid (alpha1-acid-glycoprotein)
      and serum cyfra 21-1 for non-small cell lung cancer, and perhaps plasma
      prothrombin time, might be the best laboratory parameters for the pre-therapeutic
      prognostic evaluation of the lung cancer patients, independently from the usual
      radio-clinical and histological parameters. Further prognostic evaluation studies
      are necessary in order notably to compare the prognostic values of the
      aforementioned parameters, not only aimed at evaluating the value of their pre
      therapeutic levels, but also aimed at evaluating the value of their post
      therapeutic changes. A higher pluridisciplinarity for such future publications
      also seem necessary.

PMID- 9920970
TI  - [Different procedures for the isolation of DNA from blood samples].

PMID- 9920969
TI  - [Detection of antibodies binding to myelin in 75 neuropathies associated with IgM
      gammopathy].
AB  - Polyneuropathies associated with IgM monoclonal gammopathy (IgM-MG) are the most
      frequent types of peripheral neuropathies associated with monoclonal gammopathy.
      The pathogenic relevance of IgM-MG in peripheral neuropathies is supported by
      several arguments. The more significant are pathological data on nerve biopsies
      and the demonstration of IgM antibody activity to peripheral nerve antigens,
      mainly myelin-associated glycoprotein (MAG) and, sulfated 3-glucuronyl
      paragloboside (SGPG) and sulfated 3-glucuronyl lactosaminyl paragloboside
      (SGLPG). The objective of this study was to determine the performance
      characteristics of 3 immunoassays for detection of anti-myelin antibodies in
      neuropathy associated with monoclonal IgM gammopathy. Monoclonal IgM may show
      antibody activity to carbohydrate epitopes shared by several nerve specific
      antigens. Results obtained with three reliable assay systems, indirect
      immunofluorescence for antibodies to myelin sheaths (33%), thin layer
      chromatography for anti-SGPG/SGLPG antibodies (54%) and Western-blot for anti-MAG
      antibodies (39%). Comparing the different assay systems for carbohydrate
      structure present on both MAG and SGPG/SGLPG on myelin sheath, the thin layer
      chromatography appeared to be more sensitive and reliable than Western blot.

PMID- 9920971
TI  - [Reticulocytes parameters in some hemolysis syndromes: preliminary results
      obtained with the Coulter Gen.S system].

PMID- 9920972
TI  - [Immunity to diphtheria in the North of France].

PMID- 9920973
TI  - [Fetal fibronectin as predictor of preterm birth].

PMID- 9920974
TI  - [Chromatic interferences reduction by near infrared spectrophotometry:
      application on clinical biochemistry analyzer].

PMID- 9920975
TI  - [Optodes].

PMID- 9920976
TI  - [Determinations of urine protein concentration and plasma replacement therapy].

PMID- 9920977
TI  - [Questions about a case of congenital nephrotic syndrome].

PMID- 9920978
TI  - Fate of MHC class II molecules in human dendritic cells.

PMID- 9920979
TI  - Detection and sequence diversity of Kaposi's sarcoma-associated herpesvirus
      (KSHV)/human herpesvirus 8 (HHV-8) DNA.
AB  - Detection of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human
      herpesvirus (HHV-8) has been reported frequently in patients with KS associated
      with acquired immunodeficiency syndrome (AIDS). We examined the presence of the
      KSHV sequence in 8 HIV-positive patients comprising 5 with KS, 2 with syphilis, 1
      with prurigo, and 2 HIV-negative patients with angiosarcoma. Using the polymerase
      chain reaction, we observed amplification of a DNA fragment of the expected size
      in 4 patients with KS. Sequencing analysis of the amplified fragments revealed
      several base substitutions upon comparison with the originally reported sequence.
      Our results support the hypothesis of a pathogenic role of KSHV in the
      development of skin lesions in HIV-positive patients with KS, and the sequences
      of KSHV DNA fragments isolated in this study also demonstrated strain diversity
      similar to that reported previously.

PMID- 9920980
TI  - Peripheral blood mononuclear cell proliferative response against staphylococcal
      superantigens in patients with psoriasis arthropathy.
AB  - It has been recently hypothesized that superantigens play a precipitating or
      aggravating role in psoriasis. Aside from streptococcal infection, Staphylococcus
      aureus can be sometimes detected in the tonsils of patients with psoriasis
      arthropathy (PA), although its significance in the pathogenesis of PA is still
      unknown. These focal infections are thought to be a possible triggering factor of
      the arthralgia, as well as the cutaneous manifestations, in PA. In this study, we
      have investigated the response of peripheral blood mononuclear cells (PBMC) from
      patients with PA to staphylococcal superantigens and analyzed its association
      with clinical and laboratory findings. 3H-TdR uptake by PBMC was examined after 7
      days' culture with concanavalin A (Con A), staphylococcal enterotoxin A (SEA),
      SEB and SEC1. Results showed that there was no significant difference in either
      the unstimulated or Con A-stimulated PBMC response between psoriasis vulgaris
      patients (PASI score < 10) (n = 15), PA patients (n = 11) and normal controls (n
      = 19). Among 11 PA patients, 8 patients responded most intensely to SEB, while 2
      patients showed the strongest response to SEA, and another responded mainly to
      SEC1. The PBMC response against SEB in patients with PA (38,715 719 dpm,
      stimulation index (SI); 50.2 41.4) (mean SD) was significantly higher than that
      in normal controls (23,708 466 dpm, SI; 30.9 23.8) (p < 0.05), however, the
      difference between that of patients with PA and psoriasis vulgaris (33,428 467
      dpm, SI; 42.8 30.6) did not reach significance. In addition, PBMC from psoriatic
      patients with a short episode of severe, disabling lumbago, which occured
      following sudden onset throat soreness, showed a stronger response against SEB
      (SI; 73.7 39.7), as compared with that of PA patients without such an episode
      (SI; 42.6 18.1). However this difference did not reach significance. Several
      immune abnormalities, including positive antinuclear antibodies or rheumatoid
      factor were observed mainly in the group experiencing such an episode of severe
      lumbago. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated
      that predominant expression of the T cell receptor (TCR) Vbeta 17 was commonly
      detected in both synovial tissues and paired peripheral bloods in two cases
      examined. In one case, Vbeta 12 was preferentially expressed, and in another
      case, Vbeta 10, 15 and 19 were also strongly expressed in the infiltrating
      lymphocytes in the synovial tissues. Our data raised the possibility that
      staphylococcal superantigens may also play an exacerbating role in PA.

PMID- 9920981
TI  - Follicular mucinosis successfully treated with isotretinoin.
AB  - We describe the case of a 33-year-old Caucasian male with follicular mucinosis
      successfully treated with isotretinoin. Follicular mucinosis is a primary
      idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective
      standard therapy for this disease is unknown. In our case, isotretinoin led to a
      dramatic improvement of the skin lesions in about two weeks. To the best of our
      knowledge, the benefits of isotretinoin in the treatment of follicular mucinosis
      have never been reported previously. The efficacy of this drug could be mediated
      by a regulatory effect on the infiltrating cells and/or by a modulation of the
      target organ (skin) response to the infiltrating cells.

PMID- 9920982
TI  - Antimicrobial susceptibility of Propionibacterium acnes isolated from acne
      vulgaris.
AB  - Systemic and topical antimicrobial treatment for acne vulgaris remains the
      mainstay method of therapy in Japan. Strains of Propionibacterium acnes (P.
      acnes) resistant to erythromycin (EM), clindamycin (CLDM), tetracycline (TC),
      doxycycline (DOXY) and minocycline (MINO) have been reported. The aim of the
      present study was to examine the antimicrobial susceptibility to 10 currently
      used antimicrobial agents of 50 strains of P. acnes isolated from acne lesions
      and identified using a Rap ID ANA II panel. Minimum inhibitory concentrations
      (MIC) were determined by the agar dilution method according to the criteria of
      the Japan Society of Chemotherapy. EM, ampicillin (ABPC), and CLDM were the most
      potent drugs, followed by MINO, nadifloxacin (NDFX), cephalexin (CEX), DOXY,
      ofloxacin (OFLX), and TC. In terms of the MIC80, EM and ABPC were the most
      potent, followed by CLDM, NDFX, MINO, CEX, DOXY, OFLX, TC and gentamycin (GM).
      Although most of the strains used were susceptible to the antimicrobial agents
      tested, strains of P. acnes resistant (MIC 12.5 mug/ml) to EM (4%), CLDM (4%),
      DOXY (2%) and TC (2%) were observed. In this study, no strains of P. acnes
      resistant to MINO were seen, suggesting that oral MINO is the most useful
      treatment for acne vulgaris with minimal risk of bacterial resistance.

PMID- 9920983
TI  - Vulvar amyloidosis mimicking giant condylomata acuminata in a patient with
      multiple myeloma.
AB  - We report a case of unusual cutaneous amyloidosis involving the vulva in a
      patient with multiple myeloma. Genital examination revealed a dense agglomeration
      of verrucous papules and pedunculated condyloma-like tumors. The correct
      diagnosis was established by immunohistochemical examinations that visualized
      large amounts of lambda light chains, whereas no reaction was detected for kappa
      light chains or human papilloma virus. In this way, the differential diagnosis of
      condylomata acuminata could be ruled out. Condyloma-like lesions have been
      described in patients suffering from multiple myeloma, but the present case is
      unusual because of the extensive involvement. Vulvar amyloidosis should be added
      to the list of possible presentations of myeloma-associated systemic amyloidoses.

PMID- 9920984
TI  - Skin susceptibility to dithranol: contact allergy or irritation?
AB  - A pronounced skin reaction to rather low concentrations of dithranol is often
      observed. The question arises as to whether this represents an allergic or
      irritant reaction. We performed patch tests with dithranol ointment in various
      concentrations on psoriatic patients and healthy volunteers. The results failed
      to show any clear-cut difference in skin reactions between psoriatic patients and
      healthy volunteers. One subject with a previously known skin hyperreactivity to
      dithranol showed a similar response to those of some healthy probands. However,
      subjects showing a pronounced response to rather low concentrations of dithranol
      also demonstrated a strong reaction to sodium lauryl sulphate, a standard
      irritant. We conclude that increased reactivity to dithranol most likely reflects
      an increased genuine skin susceptibility, rather than an allergic response.

PMID- 9920985
TI  - Transition between solar keratosis and basal cell carcinoma.
AB  - Transition from solar keratosis (SK) to squamous cell carcinoma (SCC) is well
      known and vastly documented. The possible relation between SK and basal cell
      carcinoma (BCC) is rarely mentioned in the dermatopathological literature. In
      order to identify the characteristics of the relation between SK and BCC, 40
      slides of the head and neck regions in which both SK and BCC had been diagnosed,
      were retrieved from a collection in the Institute of Pathology of Beilinson
      Medical Center, seen between 1984 and 1994. Gradual and continuous transition
      between SK and BCC was found in 15 (37.5%) of these 40 slides. In order to
      estimate the prevalence of this phenomenon, 73 additional slides, which had been
      diagnosed as BCC of the head and neck, were re-examined. Atypia of the spinous
      layer, as an initial marker for the development of SK, was sought in each slide.
      Revision revealed spinous layer atypia in 26 (35.6%) slides, in addition to the
      previously diagnosed BCC. In seven (9.6%) the transition between atypical spinous
      cells and BCC was gradual and continuous. A gradual and continuous transition
      between SK and BCC can be explained by the presence of pluripotent stem cells in
      the epidermis. Stem cells, following malignant transformation, may differentiate
      in different directions, resulting in both SK and BCC.

PMID- 9920986
TI  - Antibody to bullous pemphigoid antigen 1 binds to the antigen at perilesional but
      not uninvolved skin, in localized bullous pemphigoid.
AB  - We describe a 59-year-old woman who presented with vesicles, bullae and crusts on
      her lower legs. Direct immunofluorescence findings for perilesional skin showed
      linear depositions of IgG and C3 at the basement membrane zone, while no
      deposition was observed in intact thigh skin, 20 cm distant from the edge of the
      erosion. On indirect immunofluorescence study using normal human skin,
      circulating IgG autoantibody to the basement membrane zone (BMZ) was observed in
      the patient's serum at a titer of 1: 160, which reacted with an antigen located
      on the epidermal side of normal skin split by 1M NaCl and which stained the BMZ
      of the thigh skin of the patient that was negative in direct immunofluorescence
      study. Immunoblot analysis using epidermal extracts demonstrated the presence of
      IgG antibody directed to 230 kDa bullous pemphigoid antigen (BPAG1) in the
      patient's serum. These findings suggest that antibody to BPAG1 binds to an
      antigen uncovered by unknown causes at perilesional, but not at uninvolved skin
      in the present case of localized bullous pemphigoid.

PMID- 9920987
TI  - Pulmonary tuberculosis revealed by lupus vulgaris in an immunocompetent patient.
AB  - A seventy-four-year-old patient had lupus vulgaris associated with the nodular,
      confluent ulcerated type of pulmonary tuberculosis. The diagnosis had been missed
      on several occasions. The presence of cutaneous tuberculosis in developed
      countries is emphasized again. It is also stressed that chronic dermatosis of
      unknown nature in an immunocompetent patient may have a tubercular origin.
      Complete resolution of the disease was achieved after almost two years of anti
      tubercular therapy.

PMID- 9920988
TI  - Eruptive dermatofibromas and immunosuppression.
AB  - Multiple and eruptive dermatofibromas are, on the contrary, unusual. Often the
      patients who show this peculiar cutaneous pattern are referred for
      immunosuppressive therapy or they have an immunosuppressive disease. We report
      the case of a woman affected by mycosis fungoides, who developed, in 2 months, 14
      dermatofibromas on her legs. The personal history of the patient revealed a
      previous immunosuppressive treatment with systemic corticosteroids for
      interstitial pneumonia. Different etiological hypothesis have been proposed to
      explain the eruptive presence of multiple dermatofibromas and the alteration of
      the immune response, but the real mechanism is still unclear. Dermatofibromas are
      benign tumours usually encountered in dermatology.

PMID- 9920989
TI  - Contiguous inflammation of the skin.
AB  - Contiguous inflammation of the skin (CIS) is a condition comprising localized
      inflammatory skin reactions which are secondary to a source of infection
      originating in deeper anatomical structures (bacterial or sterile abscesses,
      neoplasm-associated inflammations, foreign bodies, osteomyelitis, sinusitis,
      etc.). The main clinical symptom of contiguous inflammation of the skin is an
      asymmetrical, localized and painful erythema in combination with different case
      specific symptoms. Four patients are presented below, who developed CIS caused by
      an ethmoidal carcinoma with superinfection, a postoperative mediastinal abscess,
      an odontogenic staphylococcal abscess and a purulent sinusitis maxillaris. The
      purpose of this paper is to bring attention to this condition and to offer
      guidelines for a rapid diagnosis of its underlying, potentially life-threatening,
      causal inflammatory focus.

PMID- 9920990
TI  - Tufted angioma.
AB  - Tufted angioma is a rare, slow growing, benign, vascular tumour. We describe two
      young male patients, each with a solitary erythematous plaque on the lateral
      aspect of the chest. In one case, the cutaneous lesion had been present since
      birth, in the other the tumour developed at the age of ten. Clinically appearing
      as a reddish, livid, partly papulous plaque, on histological examination they
      showed typical features of small, circumscribed, angiomatous lobules,
      particularly in the reticular layer of the dermis. These lobules were composed of
      poorly canalized, endothelial-lined vessels and solid regions. Cellular atypia
      and irregular mitotic figures were not observed. We report on our experience with
      s.c. interferon alpha treatment, in one case leading to a partial remission.
      Considering the differential diagnoses of malignant angiomatous tumours such as
      angiosarcoma or Kaposi's sarcoma, the awareness of the possibility of tufted
      angioma, which is a benign vascular proliferation, is of paramount importance.

PMID- 9920991
TI  - Urticarial vasculitis in systemic lupus erythematosus: fair response to
      prednisolone/dapsone and persistent hypocomplementemia.
AB  - Two cases of urticarial vasculitis (UV) accompanying systemic lupus erythematosus
      (SLE) are reported. Both patients developed characteristic wheal and purpuric
      lesions of UV followed by pigmentation, and histological examination revealed
      leucocytoclastic vasculitis. Although oral prednisolone was beneficial for the
      systemic symptoms and various serological abnormalities, one patient needed
      dapsone and the other needed dapsone and cyclophosphamide to control the UV. In
      both patients, hypocomplementemia with no evidence of congenital complement
      deficiency or complement consumption persisted even after all other laboratory
      data and symptoms improved.

PMID- 9920992
TI  - Contact dermatitis I. Pathophysiology of contact sensitivity.

PMID- 9920993
TI  - [Psychiatry at the turn of the 20th and 21st centuries].
AB  - The author makes an attempt at considering the most important achievements in
      psychiatry which have taken place in the global scale during the passing century,
      and the direction taken up by the development of global psychiatry in the coming
      century. The 20th century was characterised not only by the impressive
      development of science, thanks to which completely new possibilities opened up
      for global psychiatry, but also by the presence of extreme events that took place
      as a result of false ideologies such as fascism and communism. In the 20th
      century concepts like homicide, holocaust, the extermination of the mentally ill,
      experiments on people that are prohibited by the ethics of medicine and the
      elementary rules of humanity, etc. The paper includes the achievements of
      diagnosis and therapy of psychiatric disorders and the latest organisational
      solutions as well as the perspectives for further development of psychiatry. The
      author also implies the aims that psychiatry has to take up due to the numerous
      threats from our civilization: the technical-technological development, pollution
      of the natural environment, the negative changes in human values, the rising
      brutality in interhuman relations due to racial, national and religious conflicts
      and terrorism, the disappearing feeling of being safe in society, vision of
      hunger and poverty in many countries on a few continents, the danger of an
      epidemic outbreak of new unknown diseases caused by viral mutations, or genetics-
      the possible negative effects of genetic engineering (cloning of humans), etc.
      The author tries to define the role of psychiatry in preventing the threats of
      civilization.

PMID- 9920994
TI  - [Modern views on etiopathogenesis of Alzheimer's disease].
AB  - The aetiology of Alzheimer's disease (AD) remains, despite vast progress, not
      fully understood. Four genes involved in the development of the disease have been
      identified. Three fully penetrant ones (the amyloid beta-protein precursor on
      chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1)
      lead to the development of relatively rare familial form of AD. Together, they
      account for about half of this early-onset form of the disease. One genetic risk
      factor--polipoprotein E-4--is associated with late-onset Alzheimer's disease
      while at least two others are proposed. None of these genes can be by now adopted
      for use as a diagnostic or predictive test for Alzheimer's disease. Apart from
      the above, some environmental factors are also implicated in pathogenesis of the
      disease with the amyloid cascade hypothesis being the most commonly accepted as
      central. In the presented paper we have critically reviewed a literature on
      etiopatogenesis of Alzheimer's disease and discussed some practical consequences
      of the progress in understanding the mechanism of the disease.

PMID- 9920995
TI  - [Pathomorphology and pathogenesis of changes in Alzheimer's disease].
AB  - In this paper the actual issues of pathomorphology and pathogenesis of
      Alzheimer's disease are discussed. The importance of beta-amyloid is recognized.
      The linkage between late-onset form of Alzheimer's disease and the mutations of
      gene encoding the amyloid precursor protein (on chromosome 21) was found.
      Phosphorylation of paired helical filament (which are composed of tau protein)
      plays the important role. There is evidence for a strong association between
      apolipoprotein E genotype (on chromosome 19) and late-onset dementia of
      Alzheimer's type. Two more genes were recently identified: PS-1 and PS-2. Their
      mutations occur in 70-80% cases of early-onset form of the disease. There is much
      information about the role of head injury, cholinergic deficiency, estrogen,
      nerve growth factor and the decline in brain glucose metabolism. Our current
      knowledge can lead to development of prevention strategies and early recognition
      of Alzheimer's disease.

PMID- 9920996
TI  - [The psychopathological pictures of the early stages of dementia syndromes
      (vasogenic and of Alzheimer's type)].
AB  - The goal of the research is to determine the early symptoms predicting dementia
      syndromes both Vasogenic and Alzheimer type. The investigations covered: 36
      people without any psychopathological syndrome, 32 people with dementia of
      Alzheimer type and 36 people with vasogenic dementia. DSM IV criteria were
      accepted as a basis for recognition of dementia syndromes. The qualified patients
      underwent basic examination consisting of the following elements: AMDP scale (the
      estimation of psychic and somatic condition), Global Scale of Dementia, Hachinski
      scale, Blessed scale, Folsteins scale (MMS), Instrumental Activities of Daily
      Living, Physical self Maintenance Scale and two methods of the authors: Current
      Events Card and Prodromal Symptoms Card. On the basis of examinations the
      following conclusions can be stated:--persons in early stages of dementia differ
      from those without any symptoms of it by the occurrence of many
      psychopathological symptoms--not only connected with the cognitive sphere;--in
      the period preceding the development of dementia the frequency of occurrence of
      some symptoms is different according to etiology of the process (Alzheimer or
      vasogenic);--the applied clinical scales differ significantly in their value for
      the diagnosis and the estimation of intensification of dementia processes.

PMID- 9920997
TI  - [The picture of psycho-organic syndrome in multiple sclerosis].
AB  - The aim of this study is the analysis of the picture of psychoorganic syndrome in
      multiple sclerosis patients, taking into account the medical and psycho-social
      variables. Multiple sclerosis patients (N = 40) were examined with the Organic
      Brain Damage Rating Scale, used to the diagnosis of psychoorganic syndrome. The
      variables related to the course of illness, work, attitude to own illness and
      attitude of the family to the patients were also considered. The obtained picture
      of psychoorganic syndrome and the relations of the investigated variables were
      compared to the data concerning this issue, reported in the literature of the
      subject.

PMID- 9920998
TI  - [Winter depression and light therapy].
AB  - This paper is a review of the literature on winter depression--a from of seasonal
      affective disorder encountered most often. Winter depression was diagnosed first
      in the early eighties in the USA and since then it has been the subject of
      extensive research. The results of many studies confirmed the efficacy of light
      in the treatment of winter depression and at present phototherapy is considered
      the treatment of choice of this disorder. However, mechanisms underlying the
      pathophysiology of winter depression and therapeutic response to light evoke
      great controversy and hypotheses are still evolving.

PMID- 9920999
TI  - [Sexual dysfunctions in depressed patients].
AB  - Sexual dysfunction in depressed patients is an important clinical problem. Its
      complex etiology involves depressive symptoms, comorbid medical disorders,
      medication, difficulties in interpersonal relationships with partner, level of
      sexual functioning prior to the onset of illness. Also, mechanisms of action of
      psychotropic medication on sexual function are complex. Sexual dysfunction is a
      source of additional suffering for depressed patients and may contribute to poor
      compliance with treatment. It is an important challenge for the therapy of
      depression.

PMID- 9921000
TI  - [Selected psychopathological and psychological questions in an inpatient after a
      suicide attempt].
AB  - Authors have analysed 120 inpatients who committed suicidal attempt. Diagnoses in
      83 women and 37 men aged between 14 and 73 years according to DSM-V
      classification were analysed. Patients aged between 14 and 27 constituted 60%,
      while those more than 28 years old 40% of suicidal attempts. In the outcome of
      diagnoses the analysis showed that because of psychotic and nonpsychotic mental
      disturbances among them, patients after suicidal attempt needed scrutinised
      psychiatric and psychological evaluation. In consulted patients the clinical
      diagnoses distinguished: conversive reaction (54%), endogenous depression,
      dysthymic depression, personality disturbances characteropathic type and
      adolescent crises. Endogenous and dysthymic depression were predominantly found
      in persons above 28th, they constituted 26% of all diagnosed patients. In
      particular age groups no characteristic psychopathological diagnoses were found.
      The diagnosis of characteropathic type of personality disturbances was
      distributed most regularly.

PMID- 9921001
TI  - [Reactive manic syndromes].
AB  - The paper is an attempt at discussion of reactive manias--one of the least
      studied issues in psychiatry. The author present its clinical picture, the course
      of the two distinguished forms of the disorder, factors conductive to its onset
      (the rple of life stress events). The differences between "true" and
      situationally conditioned manic episodes are indicated. The paper discusses views
      of supporters and opponents of pathogenesis of manic psychosis. In modern
      classifications of mental disorders the pathology described by the author is not
      recognized as a separate disease. In the literature of the subject, the problem
      of reactive manias does not receive much attention, hence an attempt at their
      description for psychiatric theory and practice.

PMID- 9921002
TI  - [Sulpiride: the best known atypical, safe neuroleptic drug. Review of
      literature].
AB  - This is a review of literature data on a neuroleptic drug--sulpiride. Sulpiride,
      a benzamide derivative displays selective affinity for mesolimbic and
      mesocortical dopamine receptors. For this reason it is classified as an atypical
      antipsychotic drug. In clinical use, it causes undesirable side effects
      (particularly extrapyramidal, cholinolytical) less often than classical
      neuroleptics, does not cause sedation, and has activating and antidepressive
      properties. These characteristics caused that it is considered a drug of first
      choice in delusional psychoses with inhibition, depression, lowered activity,
      intensified negative or deterioration symptoms. The most serious drawback of the
      drug is the risk of symptoms caused by increased prolactine excretion, and
      increase in body weight.

PMID- 9921003
TI  - [Joint symptoms in primary hypertrophic osteoarthropathy].
AB  - Joint manifestations of hypertrophic osteoarthropathy are arthritis and
      arthralgia. Those occur at the all joints, but often at the lower extremities and
      usually are asymmetric. Swelling of the distal parts of the extremities was found
      in 52 patients (68.4%). Perimaleolar swelling proceed from periostal
      accumulation. Swollen fists are present in all patients and that phenomenon is
      characteristic sign of the disease. Swelling of the joints, perimaleolar edema
      and swelling of the distal parts of the limbs reminds of the other conditions
      (tumor, osteomyelitis, lues, Reiter's syndrome, psoriasis, lymphangitis,
      miksedema, thrombophlebitis, Caffey's disease, Engel's disease, hypervitaminosis
      A, RA, thyroid acropathia etc.), which must be taken into consideration.

PMID- 9921004
TI  - [Comparative study of the effects of auranofin and aurothiomalate on laboratory
      and clinical indicators in patients with rheumatoid arthritis].
AB  - Is there any significant difference in the effect and tolerance of the gold salts
      applied peroral and intramuscular in patients with rheumatoid arthritis (RA)? 97
      patients with RA have been included in the research. Group used auranofin
      perorally comprised 30 patients with RA, 25 women and 5 men. Their average age
      was 53.4 years, the average disease course was 9.06 years. Group used
      aurothiomalate parenterally comprised 30 patients with RA, 23 women and 7 men.
      Their average age was 52.5 years, the average duration of their illness being
      10.87 years. Control group comprised 37 patients with RA, 27 women and 10 men.
      Their average age was 58.2 years, the average disease course was 8.3 years. They
      did not use any "second line drug" or corticosteroids. During a six-month (26
      week) continuous application of the gold salts (perorally and parenterally) the
      following parameters were observed in regular intervals: the erythrocyte
      sedimentation rate, the hemoglobin level in the serum, the C-reactive protein.
      Ritchie index, the PIP extent of the fist joints and the morning stiffness span
      of the small fist joints. The tolerance of the gold salts has also been
      controlled. The results have shown that there is no any significant difference
      between two forms of the gold salts in patients with RA. The statistical
      processing of data indicated that auranofin and aurothiomalate have significant
      effect on all controlled parameters. As regard of the side effects, patients
      accepted aurothiomalate better than auranofin.

PMID- 9921005
TI  - [Occurrence of subcutaneous rheumatoid nodules in patients with rheumatoid
      arthritis in Croatia].
AB  - The subcutaneous rheumatoid nodules (RN) have been recognized by the American
      Rheumatism Association, both in 1958 and in 1987, as one of the diagnostic
      criteria (ARA criteria) among other rheumatoid arthritis (RA) symptoms. The aim
      of this research has been both to provide the incidence of occurrence of RN in
      patients with RA in Croatia and to determine its significance in making the RA
      diagnose. The test group comprised 233 patients (182 women and 51 men) with RA,
      their average age being 48.3 years in the range of 18 to 77. Both the anamnesis
      and the clinical examination have determined the occurrence of RN in 54 (23.2%)
      of 233 patients. The range of occurrences was more evident in men (31.4%) than in
      women (20.8%), though this difference was statistically irrelevant. The most
      common localization of benign rheumatoid nodules was the exterior side of elbow
      and PIP hand joints. The obtained results prove that the incidence of RN in our
      tested patients with RA can be compared with those of the earlier researches done
      in Croatia (18.1% Jajic, Vlak; 20-25% Jajic), as well as with those obtained in
      the western European countries (20% Doherty, George; 25% Ziff; 20-25% Miehle; 21%
      Wolf et al.).

PMID- 9921006
TI  - [Effect of nutrition on the clinical picture of rheumatoid arthritis].
AB  - 46 patients with RA, both sex, who had been suffering from RA within 3 and 20
      years (average 7 years), were included in our examination. Suffering from the
      basic disease for various time, 11 patients (23.9%) were stated that some
      sustenance markedly aggravate disease. Reduction diet, which was started on their
      own, had markedly positive effect on the symptoms and led to better quality of
      life. We can conclude that sustenance has an influence on disease and reduction
      diet markedly positive acts upon clinical expression of disease.

PMID- 9921007
TI  - [History of patient education in rheumatic diseases in Croatia].
AB  - The education of rheumatic patients in Croatia has begun in 1975 by introducing
      the school of back pain. Soon after that has begun the education of children with
      scoliosis. The education of patients with rheumatoid arthritis and ankylosing
      spondylitis was establish in 1985. Along with the courses of patient's education,
      there were printed a publications dedicated to the same problem. At the beginning
      there was printed a textbook Rheumatic diseases with training for rheumatic
      patients (1978.) and then textbook Jogging (1982.) and Reta (1984.). During 1994,
      there were graduated a publications dedicated to the disease having the same
      name: Rheumatoid arthritis, Ankylosing spondylitis, Uric arthritis and Psoriatic
      arthritis, which were reprinted in enlarged form (1997). Protection of the joints
      in rheumatic disease (1998.) is a new textbook for patients about correctly usage
      of the joints. Textbook Prevention of back pain and neck pain (1998.) is
      dedicated to healthy people for the prevention of pain syndromes of vertebra.
      Thus, the education was introduced in almost all parts of rheumatology and in
      whole Republic of Croatia.

PMID- 9921008
TI  - [Surgical treatment of lumbar disc hernias in athletes].
AB  - In a 7-year period (1988-1995) a series of 55 patients was surgically treated at
      our Department for lumbar disk herniation following a certain sports activity,
      i.e. sports injury. The above number accounts for 2% of the total number of
      lumbar disk patients operated upon at our Department. The majority of patients in
      our series were amateur athletes, whereas a few of them were active or
      professional athletes. The most common cause of disk herniation among our
      patients was playing soccer (13 cases), which is followed by basketball (8),
      field athletics (7), tennis (6) and handball (4). In most cases our surgical
      method of choice was flavectomy (interlaminectomy). Most commonly seen
      intraoperative finding was intervertebral disk extrusion. In some athletes the
      onset of symptoms was due to a change of their usual sports activity, for example
      a tennis player who was injured in skiing. We believe that the onset of disk
      herniation in athletes is a consequence of numerous micro traumas of the
      intervertebral disk which are further compounded by the syndrome of
      overstraining. In the case of a positive indication, surgical treatment leads to
      a faster recovery in professional athletes.

PMID- 9921009
TI  - [Acute psychoses in patients with psoriatic arthritis during treatment with
      sulfasalazine].
AB  - We present a case of hastily progress of acute psychosis in a woman patient who
      has been treating with Sulphasine because of psoriatic arthritis. The medicine
      has been taken for a short time (one month) and in low doses. We bring out this
      instructive case, which shows a possibility of development of one severe and
      unusual complication, never noted down in literature.

PMID- 9921010
TI  - [Secondary osteoporosis in men].
AB  - Although osteoporosis has been considered a disease of women, there are many
      evidences of high prevalence of osteoporosis in men, in which cases the risk
      factors are often recognised. We have presented four patients, age 39-71 years,
      with bone mineral density loss, which could have been connected with risk factor.
      Those risk factors in our patients were: malabsorpcy syndrome, heavy metal
      intoxication, aethilismus, smoking. We conclude that secondary osteoporosis in
      men appears to be an evident and growing health problem.

PMID- 9921011
TI  - [Condensing osteitis of the pubic bone].
AB  - We represent a case with development of osteitis pubis after suffering injuries
      in a man born 1940. The disease has developed during 10 years. The first symptoms
      have occurred only after 9 years. This review represent a supplement to better
      knowledge of etiopatogenesis of osteitis condensans pubis.

PMID- 9921012
TI  - [Tuberculosis of the bones and joints].

PMID- 9921013
TI  - [Intravenous drug use and transmission of AIDS].

PMID- 9921014
TI  - [Antibiotic sensitivity of bacteria isolated from the urine of children with
      urinary tract infections from 1986 to 1995].
AB  - In adults and in children urinary system infections are mostly caused by gram
      negative and rarely by gram-positive bacteria. Of gram-negative bacteria the most
      frequent cause of infections are Escherichia coli, Klebsiella species, Proteus
      mirabilis, Pseudomonas aeruginosa, Acinetobacter, Serratia etc., and of gram
      positive bacteria Enterococcus, Staphylococcus, Streptococcus agalactiae. In rare
      cases the cause of infection may also be Pneumococcus and Haemophilus influenzae.
      AIM OF THE STUDY: The aim of the study was to investigate the sensitivity to
      antibiotics of gram-negative bacteria as the predominant cause of urinary
      infections. METHOD OF THE STUDY: We isolated 20,615 bacterium species from urine
      of children hospitalized or treated as outpatients at the University Children's
      Hospital in Belgrade. Urine was collected classically, i.e. by taking the second
      clean stream into a sterile test tube or by Uricult test. The samples were
      cultured on blood plates and endo-agar. Identification was done by standard
      bacteriologic methods and when findings were dubious API-20E (bioMerieux) was
      used. Bacterium sensitivity to nine antibiotics (ampicillin, cephalexin,
      cefotaxime, chloramphenicol, gentamicin, amikacin, co-trimoxazole, nalidixic acid
      and nitrofurantoin) was assessed with disc diffuse method on Muller-Hinton agars.
      RESULTS: Based on the obtained results, Escherichia coli species sensitivity to
      amikacin, gentamicin, cefotaxime, nalidixic acid and nitrofurantoin ranged from
      90 to 100%; sensitivity to co-trimoxazole and chloramphenicol ranged from 70 to
      80%, to cephalexin from 50 to 60%, while to ampicillin it was only 20%.
      Klebsiella species sensitivity to nalidixic acid and cefotaxime was 70-85%; to
      amikacin, cefotaxime, co-trimoxazole and gentamicin 60-80%; to cephalexin and
      chloramphenicol 40-50%, and to ampicillin only 5-15%. Proteus species showed
      sensitivity to amikacin, gentamicin, cefotaxime and nalidixic acid of 90-95%; to
      co-trimoxazole and chloramphenicol 70-80%; to cephalexin and ampicillin 40-50%,
      and to nitrofurantoin 10%. Pseudomonas aeruginosa species showed the highest
      level of sensitivity to amikacin (40-50%), and somewhat lower to gentamicin (10
      40%), and a very low sensitivity to other antimicrobial drugs (10-25%).
      DISCUSSION: It may be noted from the above data that gram-negative bacteria are
      the cause of urinary infections in about 90% of cases, while gram-positive
      bacteria are the cause in only 10%, which is in accordance with data from
      literature. Of all antibiotic drugs ampicillin (a wide spectrum penicillin) had a
      very significant role in the therapy of urinary infections. However, the long
      term usage of ampicillin led to increased resistance to the drug in infections
      caused by Escherichia coli. Natural resistance to ampicillin of Klebsiella
      species limited its usage when penicillin was first introduced. Proteus mirabilis
      species, especially those isolate in primary infection, are often sensitive to
      amino penicillin. Contrary to Proteus mirabilis, indole-positive Proteus and
      Providentie species show a high resistance to these antibiotics. Due to the
      crisis in our country and the lack of other antibiotics, ampicillin was widely
      used. The wide use of the drug caused evident resistance of Escherichia coli and
      Proteus mirabilis to this antibiotic. A fall in the sensitivity of Klebsiella to
      cephalexin, gentamicin, amikacin and co-timoxazole, which occurred in 1992, has
      been explained by intrahospital circulation of multiresistant Klebsiella species.
      The sensitivity of isolated gram-negative bacteria Escherichia coli, Klebsiella
      species, Proteus mirabilis and Pseudomonas aeruginosa was the most prominent to
      aminoglycosides (amikacin and gentamicin). The most frequent mechanism of
      enterobacterial resistance to trimethoprim and co-trimoxazole involves
      dihydrofolate reductase enzyme. Comparative studies related to the administration
      of co-trimoxazole have shown that the difference in the efficacy between thes

PMID- 9921015
TI  - [Tooth diseases in the medieval population of Gracanica near Valjevo].
AB  - The analyses of the pattern of dental disease in the Late Medieval Serbian
      population from cemetery excavations in the archaeological site Grachanica were
      based on the study of tooth wear, ante-mortem tooth loss, caries, hypoplasia,
      alveolar resorption, abscesses and calculus. The total sample of all available
      skeletons with almost complete permanent dentition numbers 45 individuals. Dental
      sample comprises 178 maxillary teeth and 337 mandibular teeth. The presence of
      dental caries was scored taking into consideration the size of the lesion (four
      degrees) and its position on the tooth. The degree of tooth wear was graded into
      one of four categories: atrition of enamel only; atrition involving dentin;
      atrition up to the level of fissure at the occlusal surface of the molar teeth,
      and exposure of the pulp chamber. The cystic defects within the alveolar bone
      were recorded according to their aetiology, size and position. Radiographic study
      had not been done in order to detect periapical destruction, so the presence of
      such destruction was recognizable in advanced stages associated with the
      appearance of fistula penetrating the compact alveolar bone usually at the buccal
      side. The condition of the alveolar crest resorption, as the evidence of
      periodontal disease, was graded into three categories, and the distance from the
      cemento-enamel junction to the alveolar crest was measured. The analysis of
      dental pathology profile consisted of the two reporting methods: individual count
      method (prevalence of disease based on the number of individuals affected) and
      tooth count method (distribution of lesions frequency on tooth type and class).
      The Grachanica dentition exhibits a dental pathology profile typical of
      agricultural medieval populations in this region. Tooth wear was the most
      frequent, affecting 95% of individuals. Dental caries and ante-mortem teeth loss
      exhibit also high frequency (51% and 69%). Dental pains of low prevalence include
      abscesses (13%) and enamel hypoplasia (20%). In the material examined, the
      carious process was responsible for pulp exposure to infection in all cases of
      abscess formation. The results obtained suggest that food processing technology
      and nature of diet allowed use of abrasive in the food and that oral hygiene was
      at the low level. On the other hand, there were not a lot of people who were
      subjected to stress-induced growth disruptures. The findings reported here
      contribute to understand how dietary change and life conditions are related to
      the changing patterns of dental diseases in medieval populations.

PMID- 9921016
TI  - [Transmission of acquired immunodeficiency syndrome among intravenous drug
      abusers in Belgrade].
AB  - The prevalence of HIV infection among intravenous drug addicts (IVDAs) was 11% in
      Belgrade in 1997 (500 IVDAs). There are only two ways of transmission of HIV
      infection among IVDAs: the use of contaminated needles and syringes and sexual
      intercourse with an infected partner. We established in the counselling office
      for IVDAs that only 47.8% of them were injected with their own devices, 43%
      shared somebody's equipment, and 9.2% used other routes for drug taking. Condoms
      or safe sex were exceptional. Only 10.17% used condoms regularly; 12.5% from time
      to time and 77.32% never. Among 391 interviewed IVDAs 7% were not sexually active
      during the last year, 40% had one constant partner, 32% had intercourses with 2
      to five partners, and 21% were promiscuous (more than 5 partners over one year).
      Fifty five were seropositive against HIV. Ten of them were promiscuous and used
      no condom. There is some evidence that the majority of IVDAs after twelve years
      of post seroconversion (average age between 35 and 45), stopped their sexual
      activity. The prostitution of female IVDAs in order to finance their own and
      their partners supply of drugs is found in 3% of cases. This study can be helpful
      in implementing a selective and individual approach to some IVDAs with risk
      behaviour, who accept treatment, to prevent the spreading of infection.

PMID- 9921017
TI  - [Perception of risk for infection with the human immunodeficiency virus].
AB  - Prevention of AIDS is very complex and requires, apart from basic knowledge about
      modes of transmission and protection, individual awareness of personal risk of
      infection and modification of one's risky behavior. Perception of risk has been
      suggested as an important element of sexual behavior change among people who
      engage in behaviors that place them at risk of HIV infection. This study
      investigates perceived risk of an HIV infection among inhabitants of municipality
      of Palilula. The purpose of this study was to determine the relative accuracy of
      risk assessment, especially for those with high-risk sexual behavior and to
      assess the factors related to self perception of developing AIDS. The survey was
      conducted as a household survey in Belgrade municipality "Palilula". The design
      of the survey was based on a two-stage stratified random sample. The population
      of Palilula municipality was divided in two stratums and 840 households were
      selected from each stratum. All members of selected households aged 15-49 years
      were interviewed. Total of 2659 persons was interviewed. Self administered
      questionnaire, developed by WHO and described in the Evaluation of National AIDS
      Programme: A Methods Package 1. Prevention of HIV infection, Geneva, 1994, was
      translated and adapted for local application. For analysis of findings methods of
      descriptive statistics, chi square test and logistic regression were used.
      Statistical analysis was performed using SPSS/PC. The results showed that most of
      the respondents (1662, 62.5%) do not perceive themselves to be at risk of HIV
      infection. Interestingly, almost one quarter of the sample couldn't estimate
      personal chances of being HIV infected. Significantly larger proportion of
      respondents living in urban area than those living in rural area perceived
      themselves at risk (17.1% of urban vs. 7.7% from rural area, chi square = 54.06,
      Ir0.00). Significant differences between age groups were found for perception of
      personal risk. Respondents up to 19 and those older than 25 in more than 60
      percent and only a half of those between 20 and 24 believed that there was no
      chance they could become HIV infected. Almost 16% of respondents between 20 and
      24 believed that they had some chances of contracting HIV, also approximately one
      third of them couldn't estimate personal risk of contracting HIV infection (chi
      square = 2.10, p = 0.00)(Graphe 1). Those who engaged in sex with irregular
      partners were found to perceive themselves in higher risk then those who were
      engaged in sex only with regular partners in previous 12 months. One fifth of
      those with irregular partners estimated their chances as good versus only 10% of
      those with only regular partners. A logistic regression analysis found that those
      who believed they were personally at risk knew someone with HIV, had more
      irregular sexual partners in last 12 months, were younger, and lived in urban
      area (Table 1). People correctly perceived the risk of HIV infection as being
      minimal as most of them didn't engage in risk behavior. Risk perception was
      higher among those who had more irregular partners, younger and those from urban
      area. Most important predictor of risk perception was knowledge of HIV positive
      individual.

PMID- 9921018
TI  - [Lumbar spinal stenosis. Symptomatology and methods of treatment].
AB  - INTRODUCTION: Lumbar spinal stenosis (LSS) may be defined as any type of the
      narrowing of the spinal nerve root canal (the lateral recess), intervertebral
      foramina, or its combination. It may be local, segmental or generalized; it can
      be caused by bone or soft tissue, and the narrowing can involve the bony canal or
      the dural sac or both. The normal sagital diameter of the lumbar canal is 15 to
      25 mm and measurements below this are regarded as suggestively abnormal; a
      diameter less than 12 mm confirms the presence of stenosis. On the other hand,
      the lateral recess height less than 3 mm is suggestive, and less than 2 mm is a
      diagnostic sign of stenosis. There are two large groups of LSS: congenital
      developmental stenosis and acquired stenosis with many subgroups (Scheme 1). The
      number of surgical operations due to LSS is increased during the ensuing years
      especially in elderly persons. This is why we would like to emphasize the
      important role of this phenomenon as there are only a few published papers in
      domestic literature. MATERIAL AND METHODS: In a consecutive series of 38 patients
      with LSS diagnosed for the last five years (January 1990-December 1994), aged
      from 20 to 70 years (average age 48.55) there were 21 males (Table 1); 34 of them
      had LSS as a result of bony changes, while the rest of 4 were iatrogenic (3 after
      disc extirpation and one after laminectomy) (Fig. 1). Herniation of the nucleus
      pulposus in combination with LSS was found in 12 patients (31.57%). Local
      segmental stenosis was identified in 16 patients (42.10%). (Graph. 1) (Fig. 2);
      the others had the generalized type of stenosis involving two levels (17 patients
      44.7%); three levels (4 patients-10.52%) or 4 levels (one patient-2.63%) (Fig.
      3). As far as symptomatology is concerned 31 patients had low-back pain with
      acute radicular complaints and motor weakness as the result of lesion of one or
      two spinal roots (20 patients). There were no neurogenic claudication or cauda
      equina compression syndromes. Electromyoneurographic studies (EMNG) in surgically
      treated patients revealed preoperative signs of muscle denervation in 15 patients
      (7.42%) (Table 2); the rest of them had signs of chronic irritative lesions of
      the corresponding root. RESULTS: Twenty one patients were operated on: 19 with
      signs and symptoms of generalized type of LSS and only two with lateral recess
      stenosis (Table 2). Congenital developmental stenosis was identified in 6 young
      patients (20 to 40 years of age) (Fig. 4). Single-level laminectomy with medial
      facetectomy and nerve root decompression was performed in 10 patients, and the
      rest of them had two level or three level decompressive laminectomies with medial
      facetectomy and roots decompression (Fig. 5). Dissectomy was done in 8 patients
      (Graph 2). None of our patients had concomitant arthrodesis, or needed
      reoperation. Postoperative EMNG improvement was confirmed in 13 patients of 15
      (86.66%); this is about 61.90% in comparison to all operated patients (Table 3).
      The main complaints after the operation were: low-back pain (70%), leg numbness
      (70%), slight walking difficulties (60%); however all were able to walk more than
      500 meters. The answer to the question how they felt after the operation, 15
      patients responded to feel better or much better (71.42%), 3 felt the same
      (14.28%), and 3 felt worse than before the operation. Five patients retired
      before the operation, 7 changed their occupation taking an easier job, 9 returned
      to the same job, and none retired after the operation (Table 3). DISCUSSION: A
      certain number of patients had congenital-developmental stenosis with thickening
      of the laminae and development of short, squat pedicles with a decreased anterior
      posterior diameter of the spinal canal. There are numerous variations of this
      pattern which remain asymptomatic until later developmental changes precipitate
      the typical radiculopathy and cauda equina changes in LSS. (ABSTRACT TRUNCATED)

PMID- 9921019
TI  - [Occurrence of changes in the eye in diabetic retinopathy with significant
      myopia].
AB  - The optic disc and retinal neovascularization are less prominent and less
      frequent in myopic eyes in patients suffering from diabetes mellitus. The exact
      mechanisms of this phenomenon are not well known, but there is some evidence that
      there is a reduced blood flow in myopic eyes which is associated with less
      damaged microcirculation in eyes of patients with diabetes mellitus. The aim of
      our study was to evaluate the correlation between myopic refractive error and
      degree of diabetic retinopathy. We conducted a retrospective study in a group of
      randomized patients, divided into the following groups according to their
      refractive error: emmetropia (30 eyes), myopia simplex (30 eyes) and high myopia,
      over -6.5 dsph (21 eyes). Among patients with high myopia, seven had monocular
      myopia. All patients suffered from non insulin dependent diabetes mellitus for
      more than ten years, and their average age was 52.37-3.48 years. We did not
      observe patients with rubeosis iridis and neovascular glaucoma or patients with
      myopia less than -2.0 dsph. Our results indicated that there was no significant
      difference in the appearance of fundus between the studied groups. In all
      patients the incidence rate of non proliferative and proliferative diabetic
      retinopathy was the same as well as the absence of retinopathy (Fisher's test).
      The only exception were the patients with monocular myopia over -13.o dsph who
      had no signs of diabetic retinopathy in myopic eye, while the other, emmetropic
      eye, showed various stages of retinopathy, from severe non proliferative to
      proliferative. Some of the risk factors which influence the incidence rate of
      ocular complications in diabetic patients are well known, as are duration of
      diabetes mellitus, blood sugar level, blood pressure, ocular pressure and eye
      perfusion. On the other hand, it is also known that amblyopia, optic atrophy, low
      blood pressure in central retinal artery and retinitis pigmentosa are ocular
      conditions which are not associated with proliferative diabetic retinopathy. It
      was also noticed that complications of diabetes in high myopic eyes are less
      prominent than in emmetropic eyes. This finding is in harmony with our results.
      Sultanov et al. observed diabetic changes in the retina in 40.9% of myopic
      refraction patients, 65.2% of emmetropia cases and 70.4% of hypermetropia cases.
      The severity of involvement was less in myopia than in other types of refraction.
      In medium severe myopia, no proliferative diabetic retinopathy was observed, and
      in high myopia (10 eyes) no diabetic involvement of the fundus oculi was found.
      In anisometropia diabetic symptoms on the myopic side were either absent or
      poorly manifest. The possible cause of such findings could be the changes in
      retinal perfusion in myopic eyes and eyes in patients with diabetes mellitus. In
      1973 a lower blood flow was detected in the retina and the choroid,
      proportionally to the degree of myopia. In 1982, Perkins indicated that the
      circulation time and pulsation rate in the central retinal artery in myopic eyes
      were reduced proportionally to the degree of myopia. In cases with early diabetic
      retinopathy Coscas detected a lesser blood flow in retinal veins. On the other
      hand, it has been found that high blood pressure increases the risk of diabetic
      retinopathy. These data suggest that the reduced blood flow in high myopia is a
      protective factor regarding the occurrence of complications in diabetes.
      Anisometropia and amblyopia in cases with monocular myopia, which presents a
      particular group in our study, could be factors which also prevent the occurrence
      of proliferative diabetic retinopathy. Instead of conclusion, we would like to
      point out that pathophysiologic mechanisms of these phenomena are not discussed
      enough. It is, nevertheless, important to appropriately examine the fundus in
      patients with high myopia and diabetes mellitus, because if the complications
      appear, they may be disastrous and must be treated immediately.

PMID- 9921020
TI  - [Electrocardiographic changes in patients with chronic anemia].
AB  - It is well known and described in literature that cardiac symptoms such as
      dyspnoea, palpitations and sometimes stenocardiac pain may develop in the course
      of anaemia. The incidence of electrocardiographic abnormalities varies
      significantly in different studies ranging from 10-80%. The study is aimed to
      determine the incidence of certain electrocardiographic changes in anaemic and
      non anaemic patients (control group) before and after the stress test. PATIENTS
      AND METHODS OF EXAMINATION: A total of 60 patients divided in two groups were
      studied. Group 1 included 30 patients with anaemia, free of cardiorespiratory
      diseases and normal x ray findings. Control group comprised 30 healthy
      individuals with normal x ray findings and normal ECG findings at rest, free of
      anaemia and iron deficiency. The average haemoglobin value in the studied and
      control group was 85.6 g/L and 127 g/L, respectively. The subjects underwent
      submaximal ergometric test. The following electrocardiographic parameters were
      monitored: P wave, PR interval, R amplitude, R difference, ST segment depression,
      T wave, QT interval and QTc interval. RESULTS: In the studied group of patients
      ECG findings revealed ST segment depression at rest in one patient (3%), while in
      the control group such changes were not recorded. During the stress test, ECG
      findings revealed ST segment depression in 10 (33%) patients, as well as in 1
      (3%) patient of the control group, which proved to be statistically significant.
      Negative T wave at rest was recorded in no patient of the two groups, while after
      the stress test ECG findings revealed negative T wave in 3 (10%) patients in the
      studied group, and in the control group no changes were recorded. Prolonged QT
      interval was recorded in 8 (27%) patients of the studied group and in 1 (3%)
      patient of the control group (this finding was considered as statistically
      significant). The increased R difference was statistically significant and more
      frequent in the studied group (30%:3%). There were no increased QTc differences
      in the two groups. DISCUSSION: The total prevalence of electrocardiographic
      changes in 30 patients was 64%. The high incidence of electrocardiographic
      changes of 79% reported by Singh was most probably the result of a larger number
      of patients with more severe forms of anaemia. There were no cases with sinus
      tachycardia or sinus bradycardia; no changes in P wave length of PR interval were
      recorded. Atrial extrasystole, atrial tachycardia and atrial fibrillation
      (reported by some authors) were nor recorded. ST segment depression at rest
      occurred in one patient; it was, however, smaller than 1 mm. In 10 (33%) patients
      ST segment depression was recorded after the stress test. Singh and Volkov
      reported the similar findings, but in their series significant ST segment
      depression was also recorded at rest (which is probably due to more severe forms
      of anaemia). T wave inversion was not recorded at rest, but after the stress test
      it appeared in 3 (10%) patients. It is reported in the referential literature
      that approximately 23% of the patients express T wave inversion. Prolonged QT
      interval was evidenced in 8 (27%) patients, which is consistent with the data
      reported in literature. The increased R difference by more than 18% which is,
      according to Stankov, the result of myocardial ischaemia, was statistically more
      significant in the studied group than in the control group. CONCLUSION: Based on
      the results of the study it may be concluded that the prevalence of ECG
      abnormalities in patients with anaemia was 63%. As for the individual ECG changes
      the prevalence of ST segment depression was 33%, T wave inversion 10%, prolonged
      QT interval 27%, increased R difference 30%. The incidence of ECG abnormalities
      (ST segment depression and T wave inversion) was markedly higher after the stress
      test. The recorded electrocardiographic changes may result not only from heart
      diseases but also from anaemia as a sign of myocardial ischaemia.

PMID- 9921021
TI  - [Relation of the pressure-volume loop and mechanical energy properties of the
      left ventricle].
AB  - New biomechanical models of the left ventricle, as well as recent technological
      breakthroughs, allowed a wider use of pressure/volume loop in the assessment of
      mechano-energetic properties of the left ventricle. The most widely used
      parameter derived from the pressure/volume loop is end-systolic elastance, which
      reflects the left ventricular contractility. Additionally, pressure/volume loop
      has been proved to be useful in the assessment of left ventricular diastolic
      function. More complex parameters of left ventricular mechanisms, such as stroke
      work and potential energy, can be studied by plotting pressure/volume loop and
      lines depicting end-systolic and end-diastolic pressure/volume relations.
      Similarly, the ratio of the area contained in the pressure/volume loop, that is
      stroke work, and the level of myocardial oxygen consumption can be used in the
      assessment of the efficiency by which the left ventricle converts chemical energy
      into mechanical energy. In conclusion, the use of pressure/volume loop and its
      relationship to myocardial oxygen consumption can be very effective in the
      analysis of cardiovascular performance in various settings.

PMID- 9921022
TI  - [Malignant pleural mesothelioma. II. Modern therapeutic concepts].
AB  - In the second part of our review of malignant pleural mesothelioma, we reviewed
      current concepts of the treatment of this highly malignant disease. Although
      there are still advocates for the use of best supportive care to the treatment of
      these patients, the accumulated evidence favorizes the combined modality
      approach. Surgery, followed by postoperative external beam radiotherapy (or
      intraoperative radiotherapy), offers increased response rates and median survival
      as well as a higher percentage of patients surviving a two-year period. Although
      widely tested, both single-agent and multiple-agent chemotherapy did not succeed
      in transmitting high response rates into an improved survival. New treatment
      approaches are needed to improve poor survival in patients with malignant pleural
      mesothelioma.

PMID- 9921023
TI  - [Platelet function].
AB  - Platelets are cells which possess broad potential activities in the area of both
      physiological functions and physiological disorders. The role of platelets in
      haemostasis with vascular injury is well documented. With vascular and
      endothelial cell injury, the following sequence of platelet events includes:
      adhesion, aggregation, secretion. In addition, platelets have a certain role in
      formation of a permanent haemostatic plug and prolongation of the period of
      vasoconstriction. There is also the recent evidence of the role of platelets in
      haemostasis without vessel wall injury. It is evident that platelets play the
      essential role not only in normal haemostasis but also in wound healing,
      maintenance of normal plasma homeostasis by endocytosis as well as in
      inflammation. Platelets play a role in the following pathological events:
      atherosclerosis, tissue fibrosis, tromboembolism, graft rejection, cancer
      metastasis. A complete insight into the content of platelet depot organelles, and
      their functional possibilities requires further research in this area.

PMID- 9921024
TI  - [The role of insulin-like growth-factor binding proteins in normal and polycystic
      ovaries].
AB  - The insulin-like growth factor binding proteins are single chain polypeptides,
      that can bind insulin-like growth factors, but not insulin. They can serve as
      autocrine or paracrine regulators of the actions of insulin-like growth factor.
      The human granulosa cells produce insulin-like growth factor-II but not insulin
      like growth factor-I, while the human theca cells produce insulin-like growth
      factor-I and II. Polycystic ovarian syndrome is a disorder which is characterised
      by hyperandrogenism and anovulation. In polycystic ovarian syndrome there is a
      disorder of follicular development, with the accumulation of antral follicles
      within the ovary which fail to respond appropriately to endogenous follicle
      stimulating hormone. Significance is given to insulin-like growth factor binding
      proteins, which have an inhibitory action on follicle-stimulating hormone. No
      differences were found in the total level of insulin-like growth factor binding
      proteins follicular profiles between women with polycystic ovarian syndrome and
      without it. Serum insulin-like growth factor binding protein-I levels are lower
      in polycystic ovarian syndrome with hyperinsulinaemia, probably as a consequence
      of insulin-mediated suppression of insulin-like growth factor binding protein-I.
      Consequently, serum free insulin-like growth factor-I levels are higher. This
      alteration may cause an excessive thecal androgen production. The alterations in
      the insulin-like growth factor-insulin-like growth factor binding proteins axis
      may be one of several mechanisms that help to sustain the steady state of
      anovulation and follicular dysmaturation that are characteristic of this
      syndrome.

PMID- 9921025
TI  - [Critical review of phonosurgical methods in the treatment of sulcus vocalis].
AB  - INTRODUCTION: Sulcus vocalis is an epithelial invagination along the free edge of
      the membranous vocal fold. It interferes with the glottic closure and vibration
      pattern. Sulcus vocalis provokes voice fatigue, hoarseness and breathiness, and
      it usually appears in association with hyperkinetic phonatory pattern.
      Hyperkinesis develops secondarily, due to the compensatory effort to overcome the
      deficiency in glottic closure. The treatment of sulcus vocalis is very difficult.
      Phonosurgery is used, and is followed by postoperative voice therapy.
      PHONOSURGICAL OPERATIONS: Various surgical techniques are used in the therapy of
      sulcus vocalis. Over a 10-year period we have operated on 1550 patients with
      benign lesion of the vocal folds, of whom only 11 had sulcus vocalis (0.7%). We
      carried out various surgical techniques. a) Excision of sulcus A longitudinal
      incision of mucosa is performed along the upper surface of the vocal fold,
      distant of the free edge. Mucosa is undermined caudally, and sulcus is detached
      from its base. Sulcus is then removed by surgical scissors. With this technique
      we could not provide physiological phonation and vibration pattern, in spite of
      an apparent improvement in the voice. b) "Slicing mucosa" technique This
      procedure was suggested by Pontes, and it also begins with a longitudinal
      incision followed by creation of inferiorly based slices of mucosa. c) Excision
      plus rhyroplasty Excision of sulcus is combined with thyroplasty type I in order
      to achieve medialization of the vocal fold. It can be used in cases with severe
      glottal gap in order to improve the results of excision. d) Implants Various
      materials were used in order to enlarge the mass of the vocal fold. In our
      patients, the results of this procedure were inferior as related to excision
      surgery. DISCUSSION: The surgical procedure which is safe and accepted by the
      majority of surgeons has not yet been at our disposal. The treatment of sulcus
      vocalis should start with voice therapy, which lasts as long as the patient shows
      a progress. Only then the surgical procedure can be discussed. We obtained the
      best results with the combination of excision and voice therapy. However, the
      surgeon and the patient must be aware that the treatment is demanding and long
      lasting.

PMID- 9921026
TI  - [Laboratory diagnosis of allergic inflammation].
AB  - Monitoring of allergic inflammation includes direct examination of biopsy
      specimens from mucosa and epithelium, and indirect study by sputum,
      bronchoalveolar and nasal lavage fluid and peripheral blood. Although, some of
      these detection assays are not applicable to clinical use, it is now possible to
      measure a number of inflammatory mediators released from cells participating in
      allergic disease. The release of performed histamine from peripheral blood
      basophils challenged with specific antigen remains a valuable in vitro correlate
      of immediate hypersensitivity reactions. However, other mediators such as LTC4
      and IL-4 are also generated by basophils upon IgE dependent activation. Tryptase
      and PGD2 are released from mast cells upon activation. Eosinophils contain in
      their granules proteins that cause damage to the bronchial epithelium: MBP and
      ECP. It is possible to measure soluble markers from other cells (T cells,
      macrophages, platelets, endothelial cells) involved in allergic inflammation.
      Detection of mediators have produced data that have significantly added to our
      understanding of the mechanisms and allowed better pharmacological control of
      allergic inflammation.

PMID- 9921027
TI  - [Chemotherapy of colorectal carcinoma].
AB  - The benefit of adjuvant therapy in colorectal cancer (CRC) has been provided in
      clinical studies that have demonstrated reduction of up to 30% in a 5-year
      overall mortality in patients (pts.) with TNM stage III (Dukes' stage C)
      carcinoma. Patients with metastatic CRC are usually in a relatively good
      condition despite their advanced disease. Therefore, some clinicians wished to
      withheld the toxicity of chemotherapy until the disease became symptomatic.
      Others, however, felt it appropriate to treat patients early in the course of the
      disease. Four clinical trials may be cited addressing this clinical uncertainty
      (Table 1). Patients receiving chemotherapy had a significantly longer median
      survival in comparison with only best supportive care. The delay of the carrying
      out of systemic chemotherapy in patients with metastatic disease decreases the
      symptom free interval (2 vs. 10 months, p < 0.001), time to disease progression
      (3 vs. 8 months, p < 0.001) and median survival (14 versus 9 months, p < 0.02)
      compared to an early start of therapy [7C. Patients with metastatic colorectal
      cancer benefit from early chemotherapy in terms of survival and quality of life.
      It is clear that survival is determined by prognostic factors, mainly the
      performance status, which is a highly significant predictor of therapeutic
      response and overall survival in advanced colorectal cancer patients. Some
      authors suggests that the response is a potent and independent prognostic factor
      of survival, and that response can be used as surrogate marker of survival.
      Stable disease is a category in therapy response evaluation which is not included
      in the overall response rate. In many studies with a response rate below 20%,
      chemotherapy almost doubles the survival of patients. In most chemotherapy trials
      in advanced colorectal cancer patients, about 30-50% had stable disease. One of
      the possible reasons may be that in colorectal cancer stabilization of disease is
      a clinically relevant effect of chemotherapy. If we accept that disease
      stabilization is a clinically relevant effect of chemotherapy, should we continue
      with chemotherapy after 3 or 4 courses, and for how long, or should we stop
      treatment according to rules for stable disease, i.e. following 4 courses? The
      results of on study, which we performed in 99 patients with advanced colorectal
      cancer, indicate that under category of "stable disease" there are two different
      subpopulations of patients with quite different symptom responses as an effect of
      chemotherapy, different time to progression and possible different survival
      (Graph 1 and Graph 2). It seems that stable disease patients with clinical
      benefit could be a target group for policy "to treat until disease progression".
      The tumour response is likely to be positively correlated with improvement in
      quality of life when a patient is a symptomatic from cancer before the treatment.
      Stable disease patients without symptom improvement have no benefit from further
      chemotherapy and in these patients treatment should be stopped. Such selection
      would spare from toxicity stable disease patients without clinical benefit. We
      have no data whether different number of chemotherapy cycles in the groups of
      patients with and without clinical benefit could lead to a bias in survival
      estimation. Patients who achieved also a stable disease, but who were
      asymptomatic from the beginning of chemotherapy, and who are still asymptomatic
      after 4 chemotherapy courses, make a group for which is hard to make decision
      either to continue or to stop chemotherapy. We have treated and followed-up these
      stable disease patients as patients without clinical benefit. We have no answer
      if they could reach better time to progression and/or survival if they had been
      treated for more than 4 courses. Careful studies in the evaluation of the quality
      of life in connection with treatment effects for all stable disease
      subpopulations of patients are warranted. (ABSTRACT TRUNCATED)

PMID- 9921028
TI  - [Massive hemoptysis as a rare complication in a patient with cystic fibrosis].
AB  - A female patient, 28 years old, with massive haemoptysis as a complication of
      cystic fibrosis, is described. Cystic fibrosis is a systemic disease with common
      pulmonary manifestations. Chronic inflammatory process causes the proliferation
      of bronchial arteries, and their erosion is followed by bleeding. Transitory
      haemoptysis is common in patients with cystic fibrosis, but massive haemoptysis
      is a rare complication of this disease.

PMID- 9921029
TI  - [Drugs in the physician's bag for emergency conditions].
AB  - The list of drugs for the physician's bag depends on several factors, including
      practice location, conditions most likely to be found, costs and availability of
      drugs, organization of the emergency medicine in the region, shelf life and
      climatic vulnerability of certain drugs, population age, and size and design of
      the bag. Most of the drugs carried should be in an injectable form. However, the
      non-injectable drugs with relatively rapid systemic onset may be also included.
      Separation of drugs in the bag according to their usage may help in providing an
      organized treatment. For example, one could separate drugs for treatment of the
      following emergencies: cardiovascular, altered mental status, respiratory,
      gastrointestinal, bleeding, infections, and toxicological emergencies. The list
      of drugs needed for medical emergencies when physician makes house-calls is
      presented with short notes on their usage. Oncologic, toxicologic and pediatric
      emergencies are commented.

PMID- 9921030
TI  - [Anniversaries of the Serbian Medical Society, 1952: 80 years since the founding
      of the Society--first results and confrontations].
AB  - The celebration of the 80th anniversary of the foundation of the Serbian Medical
      Association as an important jubilee "for all cultural and social life of our
      country", "the importance of which" we many not be able to apprehend yet, "falls
      in times that show to us all the complexity of social and political situation in
      the country". In that time the first results in the creation of a system of
      medical protection and the conception of new health institutions, begun after the
      WW II on the initiative of the Association. All this relates to tasks that the
      Association proclaimed in its "resolution" for the combat against basic problems
      of public health, and above all, infant mortality and tuberculosis, as well as
      other aims that have in the meantime been realised. One can, on the basis of the
      aforesaid, speak about this period as the most important in the history of the
      Serbian Medical Association. On the other hand, with the First Congress of
      Serbian Doctors, a wide ideological confrontation was initiated that, in the
      pursuit of particular political goals, and under the motto of "constructing the
      image of a people's doctor" dominated in the time of the jubilee. This culminated
      in the confrontation with some professors at the Faculty of Medicine in Belgrade.
      Without going into analysis of this campaign that progressed with "great support
      of responsible state administration and social instructions" and all this because
      "of the construction of the image of a people's doctor" one can, from a great
      temporal distance, say that everything that has been done is the fact that the
      Serbian Medical Association did not partake in the campaign. This positive fact
      in the history of our Association is so important because these happenings did
      not disturb the work of sections and branches of the Association. The Association
      and its members continued with their activity that in the next period gave
      important results in further construction of a medical system in the country.
      This created a basis for the final shape-up of the system itself--one of advanced
      health care systems in the world.

PMID- 9921032
TI  - [Melatonin and biological rhythms].
AB  - Melatonin is synthesized and secreted by the pineal gland during the dark period
      of the light-dark cycle. This rhythmic nocturnal melatonin secretion is generated
      directly by the circadian clock located, in mammals, within the suprachiasmatic
      nucleus of the hypothalamus (SCN) and entrained to a 24 h period by the light
      dark cycle. The melatonin rhythm is thus an important efferent hormonal signal
      from the circadian clock. The periodic secretion of melatonin might thus be used
      as a circadian mediator of any system that can 'read' the message. The rhythmic
      nocturnal secretion is dependent on the SCN but the duration of the nocturnal
      production is directly proportional to the length of the dark period. It is
      through these changes in duration that the brain integrates the photoperiodic
      information, which explains the present use of melatonin on farms to control
      seasonal functions (e.g. fur, reproduction, milk production...). In essence, the
      melatonin rhythm appears to be an endocrine code of the environmental light-dark
      cycle conveying photic information that is used by an organism for both circadian
      and seasonal temporal organization. The major question arising out of this effect
      of melatonin concerns its precise mechanism of action. Our present knowledge is
      still fragmentary. As for other hormones, melatonin seems to exert its effects
      throughout different receptors. In mammals two types have already been determined
      and cloned (Mella and Mellb). Very probably others will soon be characterized and
      the list of melatonin receptor-containing structures or organs will lengthen.
      Most of our functioning (e.g. immune system, cardiovascular system...) displays
      temporal organization and disorders are known to result from a disturbance of
      such organization (e.g. during ageing). The potential therapeutic use of
      melatonin is great; however, this remains to be systematically evaluated.

PMID- 9921033
TI  - [Signaling by melatonin receptors].
AB  - Melatonin is a hormone involved in various physiological processes such as the
      circadian cycle, hormone release and immune response. High-affinity melatonin
      receptors are classified in two pharmacologically distinct groups: Mel1 and Mel2.
      These receptors have first been localized in different organs and brain
      structures and some subtypes have since been cloned. Inhibition of adenylyl
      cyclase by Mel1 receptors is the best investigated signalling pathway but cannot
      be entirely responsible for the diversity of melatonin-induced phenomena.
      Phospholipase C, potassium ion channels and guanylyl cyclases have also been
      reported to be modulated by melatonin. This review updates present knowledge of
      the characterization and signalization of melatonin receptors.

PMID- 9921035
TI  - [Development of animal models for the chronobiotics of melatonin analogs].
AB  - Melatonin is a neurohormone secreted by the pineal gland (or epiphysis). It is
      secreted only during the night whether in man or in diurnal or nocturnal animals.
      Melatonin secretion is regulated by light, which inhibits or synthesizes it. By a
      'feedback' mechanism, melatonin can regulate the suprachiasmatic nuclei which
      function like internal clocks at the level of melatonin receptors. Specific
      melatonin agonists are active in different animal models representative of sleep
      disturbances due to alterations of circadian rhythms.

PMID- 9921034
TI  - [Melatonin, a pertinent prototype for therapeutic innovation].
AB  - Melatonin fulfils most of the requirements of a typical lead compound for
      rational drug design. We have rationally modified each of its structural features
      with a view to clarifying their role in drug-receptor interactions (affinity and
      activity) and to obtain agonist and antagonist ligands which could be used as
      pharmacological tools and/or as drugs. Molecular modelling studies allow us to
      propose a pharmacophore model. The naphthalenic bioisostere of melatonin
      (agomelatin) is currently under clinical (phase II) evaluation and two other
      compounds have been selected for development.

PMID- 9921036
TI  - [Melatonin and reproduction in domestic farm animals].
AB  - Melatonin, synthetized by the pineal gland, is the chemical messenger which
      allows seasonally reproductive animals to perceive day length changes. In the
      ewe, the neural message, transformed into a hormonal one, triggers pulsatile
      activity of the LHRH neurons. About 40 days are necessary for melatonin to
      centrally stimulate the pulsatile LHRH activity. Its sites and mode of action are
      not yet known completely, but a precise hypothalamic zone has been defined in
      which radioactive melatonin binds specifically and where cold melatonin delivered
      locally stimulates LHRH activity. In the veterinary clinic, the most frequent
      mode of distribution is a sub-cutaneous implant, which induces an advancement of
      the cyclical ovulatory activity of ewes and goats. The date of fertilization is
      advanced and fecundity of females is improved. It can be used alone, or in
      association with other hormonal treatments, or after an artificial photoperiodic
      treatment. Under these conditions, it allows a quantitative and qualitative
      increase in out-of-season sperm production in rams and billy-goats. Such an
      implant is registered and marketed in France, the UK, Greece, Australia and New
      Zealand.

PMID- 9921038
TI  - [Melatonin and regulation of the cardiovascular system].
AB  - Evidence from the last 10 years suggests that melatonin may influence the
      cardiovascular system. Vascular melatoninergic receptors/sites have been
      demonstrated and are functionally linked with vasoconstrictor or vasodilatory
      effects of low (10(-9)-10(-7) M) and high (10(-6)-10(-3) M) melatonin
      concentrations respectively. Furthermore several other properties of the
      neurohormone (e.g. sympathetic inhibition) could contribute to cardioprotection.
      In vivo melatonin beneficially affects the rat cerebrovascular circulation and
      protects the rat heart following myocardial ischaemia. In this regard,
      preliminary clinical data report some alteration of the melatoninergic system in
      human stroke and coronary heart disease. Finally, the suprachiasmatic nucleus and
      possibly the melatoninergic system may modulate cardiovascular rhythmicity.
      Clinical cardiovascular data on melatonin treatment are very scarce; the effects
      of a therapy modulating the melatoninergic system on cardiovascular haemodynamics
      and rhythmicity under several physiopathological conditions need to be further
      explored together with the possible impact on cardiovascular morbidity and
      mortality.

PMID- 9921037
TI  - Melatonin and the gastrointestinal tract.
AB  - Melatonin has been detected in the digestive tract of several species and appears
      to be synthesized by the enterochromaffin cells of the gut. Although a diurnal
      rhythm of melatonin release has been observed in gastrointestinal tissues of
      birds, in other species it seems to depend on the presence of nutritional
      elements. Melatonin binding sites have been identified in the digestive tract of
      several species and it has been suggested that melatonin could act as a
      protecting agent of the gastrointestinal mucosa. Moreover, the potential role of
      melatonin as a local regulator of gastrointestinal motility has been
      investigated. It seems that at least some effects of melatonin on gut activity
      depend on an antagonistic relationship between serotonin and melatonin. The
      effects of melatonin on segmental gut transit both in the fasting and in the fed
      state, as well as on the electromyographic pattern of the small intestine in
      rats, are described.

PMID- 9921039
TI  - Putative roles of melatonin in glucose regulation.
AB  - The role of melatonin in human glucose regulation is poorly understood. Under
      normal conditions, glucose tolerance is modulated by circadian rhythmicity and
      sleep, two central nervous system processes which may be influenced by melatonin.
      In the presence of a constant stimulus (e.g. intravenous glucose infusion), blood
      glucose levels increase from morning to evening and further increase until the
      middle of sleep, when a decline towards morning levels is initiated. This 24-h
      variation is due to coordinated changes in insulin-dependent and non-insulin
      dependent glucose utilization (e.g. by the brain), in insulin sensitivity and in
      insulin secretion. Causative roles for the 24-h cortisol rhythm and for sleep
      related growth hormone release have been clearly identified. Changes in sympatho
      vagal balance at the level of the pancreas could also be implicated but have not
      been investigated. Melatonin is likely to play an indirect role in the mechanisms
      underlying glucose regulation via its actions on the suprachiasmatic nucleus and
      on sleep regulation.

PMID- 9921040
TI  - [Melatonin and aging].
AB  - Melatonin is a hormone secreted mainly by the pineal gland but also by the
      retina. It is synthesized from tryptophan and its characteristic circadian rhythm
      is ruled by light through the control of two limiting enzymic activities N-acetyl
      transferase and hydroxyindole-O-methyl-transferase. In man--as in all studied
      species--its maximum plasma concentration is at night. Therefore it is considered
      as a signal transducing information on solar light within the organism thus
      providing the temporal framework upon which metabolic pathways are organized.
      Since its circulating levels decrease with ageing the question arises as to the
      origin and/or the consequences of this decrease, as well as the possible
      beneficial effects which could result from its administration in ageing humans.

PMID- 9921041
TI  - Complex effects of melatonin.
AB  - The primary function of melatonin in mammals is to transmit information
      concerning light-dark cycles for the organization of day length dependent on
      seasonal functions. There is little evidence for an essential role in circadian
      organization in mammals, in contrast with lower vertebates. It does, however,
      appear to reinforce physiological functions associated with darkness. Free
      running blind and indeed sighted subjects show a close correlation between
      maximum sleepiness, minimum temperature and peak melatonin secretion. In humans
      exogenous melatonin will lower core body temperature and induce transient
      sleepiness in suitable doses and conditions. Similarly it will shift circadian
      phase, as assessed by a number of marker rhythms. These phase-shifting properties
      may not be sufficient to synchronize all circadian rhythms in the absence of
      other time cues. In most normal sighted subjects and a number of blind subjects
      the sleep-wake cycle can be 'stabilized' to a 24 h period by daily melatonin
      administration in free-running conditions. However, anomalous results have also
      been obtained. Daily administration of melatonin (5 mg) appears to fragment sleep
      in some subjects treated in dim light conditions. This observation requires
      further investigation since it may compromise the therapeutic potential of both
      melatonin and its agonists.

PMID- 9921042
TI  - [Seasonal depression].
AB  - Seasonal affective disorder (SAD) is characterized by annual major depressive
      episodes. It occurs most commonly in young women during autumn and winter with
      full remission during the following spring. The patient's mood is a combination
      of depression and anxiety accompanied by fatigue, loss of libido, and a reduction
      of socialization. Most of these patients complain of atypical vegetative symptoms
      (e.g. hypersomnia, carbohydrate craving, and weight gain). Hypotheses on the
      underlying mechanisms of these behavioural disorders indicate that environmental
      variables, e.g. climate, latitude, light, and changes in neurotransmitter
      function that occur naturally with the seasons, may be important. Phototherapy is
      being used increasingly for the treatment of SAD. The antidepressant response is
      contingent on the exposure of the patients' eyes to light. The biological basis
      of the diverse psychological and biological changes in SAD and the underlying
      mechanism of action of phototherapy are still unclear and require further study.

PMID- 9921043
TI  - [Tentative intoxication with milnacipran].

PMID- 9921044
TI  - [Hyperprolactinemia induced by indoramin].

PMID- 9921045
TI  - [Carbamazepine overdose following administration of sertraline: relation to
      serotonergic syndrome?].

PMID- 9921046
TI  - [Fluvoxamine and convulsive syncope: case report].

PMID- 9921047
TI  - [Cataract and simvastatin: case report].

PMID- 9921048
TI  - [Cutaneous anesthesia with a lidocaine-prilocaine combination (EMLA) and systemic
      toxicity].

PMID- 9921049
TI  - [Veno-occlusive disease following chronic ingestion of drugs containing senecio].

PMID- 9921050
TI  - [Persistent cerebellar syndrome after treatment with lithium and a neuroleptic].

PMID- 9921051
TI  - Unusual combination of erythroderma and agranulocytosis induced by carbamazepine.

PMID- 9921052
TI  - [Acute adrenal insufficiency caused by laxatives].

PMID- 9921053
TI  - [Changes in ceftazidime concentration in the CSF following overdose in acute
      kidney failure].

PMID- 9921054
TI  - [120 years' of the Military Hospital in Nis].

PMID- 9921055
TI  - [Treatment of breast carcinoma at the Military Hospital in Nis 1986-1995].

PMID- 9921056
TI  - [Surgical treatment of carcinoma of the colon and rectum 1964-1995].

PMID- 9921057
TI  - [Premedication in peripheral block anesthesia].

PMID- 9921058
TI  - [The effect of diabetes on complications in acute myocardial infarct].

PMID- 9921059
TI  - [Use of prokinetic agents in hypotonic dyskinesia of the biliary tract].

PMID- 9921060
TI  - [Hemorrhagic renal cysts--diagnostic and therapeutic approach].

PMID- 9921062
TI  - [Refraction and poor vision in preschool children].

PMID- 9921061
TI  - [Percutaneous translumbar sympathectomy guided by computer tomography].

PMID- 9921064
TI  - [Medico-psychologic aspects of dental pain].

PMID- 9921063
TI  - [Personal experience in the diagnosis of schistosomiasis].

PMID- 9921065
TI  - [The anterior tarsal tunnel syndrome--case report].

PMID- 9921066
TI  - [Subclavian steal syndrome].

PMID- 9921067
TI  - [Case report of an unusual attempted suicide--parasuicide].

PMID- 9921068
TI  - [Clinical manifestations of acute cytomegalovirus infections in immunocompetent
      individuals].

PMID- 9921069
TI  - [A severe form of falciparum malaria].

PMID- 9921070
TI  - Oxidative stress and Parkinson's disease.
AB  - The aim of this study was to determine the baseline state of oxidative stress
      indices in drug-naive patients with Parkinson's disease (PD). Cerebrospinal fluid
      (CSF) and peripheral blood samples of 31 subjects, in disease stages I-III,
      according to Hoehn & Yahr scale, were analyzed and compared with the control
      group. Highly significant increase of malondialdehyde content in CSF (p < 0.001)
      was found, as well as significant differences in peripheral blood parameters:
      malondialdehyde content was increased in patients with PD (p < 0.05), and also
      the activities of antioxidative defense enzymes, gluthathion reductase, Cu, Zn
      superoxide-dismutase (p < 0.05), and the production of highly reactive oxygen
      species-superoxide radical (p < 0.05). Those findings indicated the important
      role of oxidative stress in Parkinson's disease evolution and progress. The
      findings of increased amount of reactive oxidative species (malondialdehyde
      content and superoxide radical production) in peripheral blood, and excessive
      activity of protective enzymatic systems (gluthathion reductase Cu, Zn-superoxid
      dismutase) suggested the additional systemic reaction related to chronic
      oxidative stress state in the brain.

PMID- 9921071
TI  - [Analysis of antihypertensive therapy in patients before acute cerebral ischemic
      disease].
AB  - The adequacy of therapeutic program for hypertensive disease in the patients with
      ischemic brain disease was analyzed in the study related to the administration of
      the drugs divided by the groups of antihypertensive drugs. The results had
      demonstrated that in over 50% patients the therapy had to be changed by
      introducing at least one hypertensive drug from the other group. In many cases
      were observed inadequate doses of antihypertensive drugs and the prescription of
      antihypertensive drug in minimal dose, although therapeutic response was not
      adequate. In significant number of cases (over 80%), the patients were
      irregularly taking the prescribed therapy, and only 18% had the regular controls.
      The results of this investigation indicated that on one side did not exist the
      adequate therapeutic program for hypertension control and on the other the
      significant number of patients irregularly used the proposed therapy and did not
      control the disease regularly.

PMID- 9921072
TI  - [Histopathologic changes in the kidneys in patients with asymtomatic pathologic
      findings in urine].
AB  - The authors had analyzed histopathologic changes in the kidneys of patients with
      asymptomatic abnormalities of urine analyzing if they were correlated with the
      type of pathologic finding in urine. Retrospective study comprised a total of 76
      patients with asymptomatic urine abnormalities. In all three groups of patients,
      formed upon the type of pathologic finding in urine, were determined
      heterogeneous histopathologic changes, and different types of glomerulonephritis,
      respectively. The most frequent histopathologic finding was IgA nephropathy,
      observed in 16.7% patients with isolated proteinuria, in 50% patients with
      isolated microscopic hematuria and in 55.9% patients with associated urine
      abnormalities. In distinction from the other two groups of patients, in the group
      of patients with isolated proteinuria normal histologic finding was very
      frequently found (25% patients), and in group of patients with associated urine
      abnormalities were observed more severe histopathologic forms of
      glomerulonephritis, such as membranoproliferative glomerulonephritis. It was
      concluded that different types of glomerulonephritis most frequently caused
      asymptomatic abnormalities of urine in younger patients.

PMID- 9921073
TI  - [Magnetic resonance findings and cerebrospinal fluid parameters in the evaluation
      of blood-brain barrier status and multiple sclerosis activity].
AB  - The diagnosis of disseminated demyelinating disease of central nervous system
      (DDD CNS) was established on clinical criteria, cerebrospinal fluid (CSF)
      analyses, electrophysiological and neuro-radiological examinations. The aim of
      this investigation was to perform an analysis of the state of blood-brain barrier
      and activity of demyelinating process in the patients, by the comparison of CSF
      findings and results of magnetic resonance (MR) examinations using paramagnetic
      contrast. Investigations were performed in 30 patients with DDD CNS in the phase
      of clinical impairment, without immunosuppressive/immunomodulatory therapy in the
      last 3 months. The results revealed the absence of correlation between CSF and MR
      findings, as in connection with the damage of blood-brain barrier, so in relation
      to immunologic activity of the disease. In the study are discussed the causes of
      these disparities that are the probable sequela of heterogenicity of
      physiopathologic events and disease forms inside DDD CNS.

PMID- 9921074
TI  - [Personal experience in the diagnosis and treatment of hepatic echinococcosis].
AB  - Human echinococcosis is endemic disease that occurs in some regions of
      Yugoslavia. It is caused by tapeworm Echinococcus granulosus, whose larva can
      develop cysts in liver and other organs. In the study were presented 119 patients
      with hepatic echinococcosis, 57 (47.9%) females of average age 41.4 years (9-80)
      and 62 (52.1%) males of average age 35.5 years (6.72). Primary echinococcosis was
      present in 75 (63%), and recurrent in 44 (37%) patients. Right lobe of liver was
      affected in 83 (69.7%), left in 17 (14.3%) and both lobes in 19 (16%) of cases.
      The complications of hepatic echinococcosis such as cyst infection, cholestasis,
      cyst rupture in biliary tract and liver fibrosis were observed in 20 (16.8%)
      patients. Indirect immunofluorescence antibody test was positive in 91 out of 119
      (68.1%) patients, and hemagglutination inhibition test was positive in 56 out of
      77 (72.7%) patients. Surgically were treated 57 (47.9%) patients, and 41 of them
      received antihelminithic drugs pre and/or postoperatively. Disease recurrence was
      observed in 4 (7%) patients. Percutaneous puncture and drainage of echinococcus
      cyst with simultaneous albendazole administration was performed in 12 (10%)
      patients. In three of them liver abscess was developed during drainage, and for
      that reason, two patients had to be surgically treated. Ten (83.3%) patients were
      completely cured. Medicamentous therapy as the only treatment was used in 31
      (26.1%) patients, 9 patients received mebendazole, 19 received albendazole and 3
      patients received praziquantel. The success was achieved in 10 (32.3%) patients.
      Out of the total number, 19 (16%) patients were not treated at all. Surgical
      removal of the cyst takes a leading place in the treatment of hepatic
      echinococcosis. However, in well-selected cases and in the patients with high
      surgical risk, antihelminithic therapy and percutaneous drainage of echinococcus
      cyst are of more significance.

PMID- 9921076
TI  - [Neuroradiologic diagnosis of space compression processes caused by orbital
      tumors or pseudotumors].
AB  - In thirty-year period are presented 110 patients with spatio-compressive orbital
      processes diagnosed by ophtalmoradiological methods. Out of those, 100 patients
      were surgically treated and histopathologically verified in our institution. All
      the entities of spatio-compressive processes are presented, benign and malignant
      tumors as well as pseudotumors of inflammatory and vascular nature. All the
      methods known in the world up to day are chronologically alleged, from classic to
      modern digital methods, as well as their diagnostic efficacy. The most
      efficacious algorhitm is established in the choice of radiological examination
      procedures on the basis of former experience. The collaboration of
      neuroradiologist, ophthalmologist and neurosurgeon was of the utmost significance
      in solving the spatio-compressive orbital processes.

PMID- 9921075
TI  - [Use of fibrin glue prepared from recycled cryoprecipitate in experimental liver
      surgery].
AB  - Fibrin glue (FG) is a two-component biologic system with adhesive, sealant and
      topical hemostatic properties, containing fibrinogen (Fg), factor XIII (FXIII),
      fibronectin (Fn), thrombin, some antifibrinolytic agent if needed and ionized
      calcium. In this study, FG component 1 was prepared by recycling
      cryoprecipitation from single-donor plasma. The mean concentrations of Fg, FXIII
      and Fn were: 54.2 +/- 19.9 g/l, 8.03 +/- 2.3 IU/ml and 3103.1 +/- 148.91 mg/l,
      respectively. Horizontal tensile strength of FG was 1.076 +/- 0.18 N/cm2 in the
      average. Using a rat model, the efficacy of the FG-treatment in liver surgery was
      evaluated on the basis of the 24 hour survival ratio and hematological parameters
      of the experimental animals and control group. Survival of rats subjected to
      partial and total lobectomy and FG-treated was significantly (p < 0.001) higher
      than in FG-non-treated animals. Survival of animals subjected to liver incision
      was not significantly different, although the differences in hematological
      parameters were significant (p < 0.001 to p < 0.09) in favor of FG-treated
      animals. Our findings confirmed that high quality FG can be prepared by recycling
      cryoprecipitation from single-donor plasma--with sufficient yield of fibrinogen,
      FXIII and fibronectin and with the risk of disease transmission not greater than
      with the use of single unit of blood or plasma--which have efficient hemostatic
      and therapeutic properties.

PMID- 9921077
TI  - [The role of hyperbaric medicine in the treatment of cerebral and myocardial
      ischemic disease].

PMID- 9921078
TI  - [Review of the regulations on quality control of human albumin].

PMID- 9921079
TI  - [Surgical treatment of chronic neurogenic pain--clinical use of the DREZ
      operation].

PMID- 9921080
TI  - [Amiodarone--pro and con].
AB  - OBJECTIVE: To compare and evaluate the data for and against the use of
      antiarrhythmic agent amiodarone in known cardiological indications. DATA SOURCES:
      A MEDLINE search was used to identify the articles dealing with amiodarone,
      published in the last 15 years. STUDY SELECTION: Articles and studies
      (uncontrolled retrospective and controlled prospective), as well as case reports
      speaking decidedly for or against amiodarone were scrutinized. DATA EXTRACTION:
      Simple search, no particular conditions. CONCLUSIONS: Despite very numerous and
      serious side effects amiodarone is an extraordinary drug and can be recommended
      for use, provided that the physician is very well acquainted with all
      implications of its use. Large number of studies on a significant number of
      patients has proven the efficacy of amiodarone in supraventricular and
      ventricular arrhythmias of various origin. The drug is particularly suitable for
      the treatment of ventricular arrhythmia in patients with serious heart failure
      and impaired function of the left ventricle. It was successfully used in the
      treatment of malignant ventricular arrhythmias. In patients after myocardial
      infarction, intravenously administered amiodarone improved the chances of
      survival as well as the condition of arrhythmia, preventing spreading of the
      infarction. It is very convenient against ventricular arrhythmia after the
      successful resuscitation. Short-lasting intravenous administration of amiodarone
      does not cause serious side effects.

PMID- 9921081
TI  - [Neurologic disorders in a patient with autoimmune hemolytic anemia].
AB  - Completely different entities might be with the same possibility in the baseline
      of interweaving of symptoms and signs of nervous system damage. One of them, the
      deficiency of vitamin B12 very frequently causes megaloblastic anemia and
      funicular myelosis. In the case of our patient, after the clinical picture of
      hemolytic anemia was revealed, by slow-progressive course was developed
      neurologic deficiency that, according to its features, could have the deficiency
      of cobalamin and folic acid in its etiologic background. On the basis of disease
      course, clinical finding, numerous clinical investigations so as the reaction to
      applied therapy it was assumed that the patient had besides confirmed autoimmune
      hemolytic anemia the pernicious anemia as the associated cause of anemic syndrome
      and the basic reason of the development of neurologic deficiency. Described is
      the frequent associated occurrence of pernicious anemia and antiglobulin positive
      hemolytic anemia, so as the significant association of pernicious anemia with the
      deficiency of immunoglobulins that was otherwise observed in our patient as the
      permanent IgA deficiency.

PMID- 9921082
TI  - [Recurrent abscessing pneumonia caused by Nocardia].
AB  - In female patient, 19 years old, disease occurred when she was 5. Thoracotomy
      with atypical resection of lung part was performed for the abscess in right lobe.
      Nocardia was bacteriologically confirmed. In the next 3 years, she was treated
      for pneumonia several times. When she was 19, abscess-forming pneumonia that
      recurrently occurred after the antibiotic therapy cease was established in right
      lobe. Nocardia was isolated by bronchoscopically taken aspirate,
      bacteriologically stained by Gramm, Ziehl-Neelsen and Kinyon and cultivated on
      several bacteriological and mycological media. She has been treated by antibiotic
      combination (sulfamethoxazole + trimethoprim and amoxicillin + clavulanic acid
      and minocycline) for 10 months. Subjective discomforts disappeared after the
      therapy, biohumoral findings were normal, and smaller pleuropulmonary adhesions
      on the right side could have been radiologically observed.

PMID- 9921084
TI  - A clinico-radiological correlation of breast diseases during lactation and the
      significance of unilateral failure of lactation.
AB  - Over a period of three and a half years, 58 patients who for various reasons had
      both ultrasonography and mammography during lactation were analyzed to identify
      and correlate breast diseases, if any, with the clinical symptomatology. The
      clinical symptoms were breast pain, mass and/or unilateral failure of lactation.
      Twenty-one (21) out of 58 (36%) had abnormal findings. The commonest was
      galactocele (N = 9) which usually presented with breast pain and a mass.
      Unilateral failure of lactation and in particular refusal of the infant to suckle
      (infant rejection sign) was associated with breast lesions such as malignancy (N
      = 4), breast abscess (N = 2) and infected galactocele (N = 2). Mammographically,
      the affected breast showed a significantly reduced ductal pattern as well as
      significant pathology such as a mass. Symptomatic patient with bilateral
      successful lactation had benign breast lesions such as simple galactocele and
      fibroadenoma. Unilateral failure of lactation in a symptomatic breast may signal
      serious breast pathology during lactation and a thorough radiological evaluation
      including core biopsy of solid lesions and mammography is therefore suggested.
      Patients with breast pain and or mass but with bilateral normal lactation tend to
      have benign breast changes and ultrasound alone was adequate in evaluating these
      patients.

PMID- 9921083
TI  - [Angiokeratoma circumscriptum].
AB  - We have presented a 12-year-old boy with angiokeratoma circumscriptum on his left
      knee. The lesion first appeared at the age of eight as a dark brown nodus with
      the verrucous surface. It bled easily even after mild trauma this being a
      principal reason for the hospital admission and surgical excision in toto.
      Pathohistological examination confirmed the clinical diagnosis. Differential
      diagnosis, clinical and pathohistological findings, as well as therapy of the
      disease have been discussed in some detail.

PMID- 9921085
TI  - Complications following sedation of paediatric oncology patients undergoing
      radiotherapy.
AB  - Sedation is often required to achieve immobilisation of small children during
      radiotherapy to avoid irradiation of normal tissues during the course of
      treatment. At the University College Hospital, Ibadan radiotherapists provide
      sedation for such patients with administration of parenteral and/or oral
      promethazine, diazepam, chlorpromazine and paraldehyde. This retrospective review
      of 84 children aged 1 month to 6 years who received sedation for radiotherapy
      over a period of twenty-one to twenty-eight days showed that 48% had
      complications. These included injection cellulitis (85.3%), injection abscess
      (4.87%), paresis of the lower limb (7.3%), aspiration pneumonia (2.4%).
      Anaesthetists in developing countries should be encouraged to extend their
      expertise in caring and resuscitation of sedated or unconscious patients to the
      radiotherapy unit. This will allow for the use of a wider variety of sedative
      agents and better monitoring as well as minimise or eradicate complications.

PMID- 9921086
TI  - Contraceptive method choices among adolescents in a Nigerian tertiary
      institution.
AB  - This study was undertaken to describe adolescents, use of contraceptive methods
      and to examine factors that motivate their choice. Face-to-face interview of
      single, randomly selected 971 males and females aged 18-24 years in a Nigerian
      tertiary institution was conducted. Among sexually active males and females 72
      percent and 81 percent respectively had ever used contraception. The commonest
      methods ever used by the males and females respectively were the condom (43
      percent) and rhythm (31 percent). While females were mainly motivated by
      pregnancy prevention irrespective of the sexual relationship, the males were more
      concerned about disease prevention in unstable sexual relationships. However,
      adolescents whose choice was motivated by disease prevention did not choose the
      condom significantly more frequently than other methods. The college clinic,
      complimented by other programmes, should be strengthened for reproductive health
      services.

PMID- 9921087
TI  - The diagnostive evaluation and surgical management of soft tissue sarcomas.
AB  - A retrospective case note study of 40 patients presenting with soft tissue
      sarcomas at different sites was carried out covering the period between January
      1985 and December 1995 at the University Teaching Hospital, Jos Nigeria. The
      hospital incidence was 4 cases a year males are afflicted more often than females
      in a ratio of 2:1. The mean age at presentation was 30 years with a range of (4
      65) years. The main modes of presentation were tumefaction 95% and ulceration
      50%; the mean duration of symptoms before presentation was about 6 months.
      Lesions were distributed mainly in the lower limbs in 65% of cases; thirty-four
      percent of the total number of cases were low grade while 48% were high grade
      malignant lesions. Incisional biopsy was the most favoured method of confirming
      the diagnosis in these lesions while surgery was the mainstay of treatment in
      stages 1 and 2 lesions. Radical excision especially in the lower limb is
      advocated for curative purposes. The results of palliative surgery are no doubt
      gratifying to patients with advanced lesions but the relative place of surgery,
      radiotherapy and chemotherapy in the 5-year survival of these patients continued
      to be conjectural. Prospective studies are badly needed in this respect.

PMID- 9921088
TI  - Pattern of homicides in Nigeria--the Ile-Ife experience.
AB  - Homicide victims were studied in Ife, Nigeria, between October 1977 and December
      1988. Two hundred and two cases were analysed during the period. Male to Female
      ratio was 4.6:1. The peak age of victims was between 20 and 40 years; 37 percent
      were killed with firearms, 35 percent with cutting and piercing instruments and
      18% by blunt force. These findings tally favourably with observations in other
      places.

PMID- 9921089
TI  - Effect of sun-drying and chemical disinfection on contaminated cleaning cloth.
AB  - In domestic environment, cross-contamination by contaminated cleaning cloth
      represents an infection hazard. Could disinfectant use, detergent wash and rinse,
      and proper sun-drying be a panacea for cross-contamination? This is the fact
      finding goal of this work. A sterilized towel (66.5 cm) was used to mop the
      eating tables of Nnamdi Azikiwe University cafeteria for 3 days, then aseptically
      collected and cut into six equal size, each for: estimation of total bacterial
      count; determination of the effects of detergent, sun-drying strength Ringer's
      solution was used as neutralizing medium. Seven organisms, Escherichia Coli,
      Staphylococcus aureus, Proteus. Bacillus, Klebsiella, and pseudomonas species
      were isolated from the mop. The total bacterial count was 2.9 x 10(12) cfu/cm2.
      However, detergent washing cum sun-drying proved effective in reducing, to
      acceptable standards, the bacterial numbers and types. Disinfectant use gave a
      second best result. The present hygienic practices in student's cafeteria and
      other similar places in Nigeria and elsewhere (where mop is not properly washed
      and sufficiently sun-dried before re-use) may not be quite healthy after all.

PMID- 9921090
TI  - The productivity and impact of psychiatric research on development of mental
      health services in Nigeria.
AB  - A study was conducted on three decades of medical research at the College of
      Medicine of the University of Ibadan (UCH) Nigeria, (1948-1980) and the perceived
      impact of this research on the development of psychiatry and mental health
      services in Nigeria. The Department of Psychiatry, UCH was for many years a unit
      in the Department of medicine but its scientific publications which commenced in
      the late fifties ranked seventh out of the twelve departments in the Faculty of
      Clinical Services of the College. Psychiatric researches during this period were
      mainly directed to the problems related to the scientific practice and
      acceptability of psychiatry as a distinct discipline of medicine. The research
      studies created a positive awareness which led to the establishment of more
      Departments of Psychiatry, several specialist psychiatric institutions and
      psychiatric residency programs in the country. Western type treatment of
      psychiatric disorders was accepted wholly or as additional treatment to the
      traditional methods.

PMID- 9921091
TI  - Obesity--an overview.
AB  - Obesity or being overweight, often resulting from overfeeding, has become a
      problem of public health magnitude not only in the developed countries but also
      in the developing countries. The literature has been extensively reviewed to give
      an overview of the health problems associated with this disorder. Some of these
      health hazards include hypertension, stroke, coronary (ischaemic) heart disease,
      diabetes mellitus, premature death, increased risk of cancer and at surgery. The
      causes, the types, the mode of assessment of the degree of obesity and the
      various methods of managing obesity with particular emphasis on dieting, exercise
      and the possible use of drugs (anorexiants) as well as surgery, as adjuncts, have
      been considered.

PMID- 9921092
TI  - Diagnosis, management and prognosis of obstructive jaundice in Ile-Ife, Nigeria.
AB  - A 5-year review of 50 patients, 28 males, 22 females, with a mean age of 42
      years, operated for obstructive jaundice at Ile-Ife, Nigeria was undertaken.
      Neoplasms of the pancreas, liver, and bile duct were the common causes.
      Percutaneous Transhepatic Cholangiography (PTC) with hypotonic duodenography was
      excellent in determining the underlying lesions. Pancreatic carcinoma accounted
      for 28% of cases, cholelithiasis 24%, hepatoma 22%, metastatic cancer 14%, bile
      duct carcinoma 10%, and traumatic pancreatic pseudocyst 2%. The patients with
      malignancies were older than those with biliary calculi. Biochemically, elevated
      alkaline phosphatase, and conjugated hyperbilirubinaemia, particularly in
      malignant obstructions, were diagnostic. Benigh bile ductal obstructions were
      surgically managed without any mortality. Malignant obstructions were surgically
      managed without any mortality. Malignant obstructions with their advanced
      presentations were less successfully managed. Biopsy alone or palliative bypass
      procedure could only be offered and the survival rate was dismal.

PMID- 9921093
TI  - Tube caecostomies--a fresh look in paediatric practice.
AB  - We have evaluated our practice of tube caecostomies in 21 children operated on
      from January 1982 to December 1987 at the Royal Hospital for sick children,
      Bristol, and 18 children operated on at the Paediatric Surgery Unit of the Korle
      Bu Teaching Hospital, Accra, Ghana from January 1989 to December 1996. The
      indications for surgery were, Hirschsprung's disease (36) and idiopathic
      constipation (3). The definitive procedures involved were Duhamel's procedure in
      36, Soave's procedure in 2 and colo-anal anastomosis in 1 case. This method
      reduces the total number of surgical operations required by the child from 3 to
      2, thereby reducing the total period of hospitalisation for the child. A sample
      technique of tube caecostomy is described in 39 children undergoing corrective
      surgery.

PMID- 9921094
TI  - Acute appendicitis and dietary fibre intake.
AB  - It has been postulated that acute appendicitis is the first serious disease to
      emerge with the adoption of fibre-depleted diets. The incidence of acute
      appendicitis is rising in Africa and this has been attributed to socio-economic
      advancement and the adoption of low residue diets. The aim of this study was to
      determine whether income levels and the level of dietary fibre intake play any
      role in the rising incidence of acute appendicitis in Ghana. Between June and
      November 1997 patients aged 13 years and above with acute appendicitis were
      studied. Their monthly net income levels or those of their parents if they were
      minors were ascertained and a dietary fibre questionnaire completed on each
      patient in order to assess his or her dietary fibre intake. The clinical details
      of each patient were recorded on a proforma. One hundred and seventy-three
      patients, 128 males and 45 females, mean age 29.2 (range 13-75) years were
      studied. 14 percent presented within 6 h, 46.8 percent within 24 h and 41.6
      percent after 2 or more days. 53.2 percent had acute appendicitis and 42.8
      percent presented with complicated appendicitis. The appendix was normal in 4.0
      percent. Two patients died (1.2 percent). 61.3 percent of patients were low
      income earners and 38.7 percent were high income earners. The overall dietary
      fibre intake was 39.4 g per day with no significant difference in fibre
      consumption between low income earners (39.0 g/day) and high income earners (43.5
      g/day). We conclude that dietary fibre may not be the important factor in acute
      appendicitis and other luminal and/or morphological factors may be predisposing
      factors.

PMID- 9921095
TI  - Paediatric AIDS in Jos, Nigeria.
AB  - A retrospective study of all children admitted with the diagnosis of acquired
      immunodeficiency syndrome (AIDS) at Jos University Teaching Hospital (JUTH)
      between August 1995 and October 1996 was carried out. Forty three (1.5% out of a
      total of 2793 children were diagnosed with HIV infection during the study period.
      However, only the records of 23 out. Of the 43 positive cases were available for
      analysis. Of the 23 cases whose records were available, 8 presented in 1995,
      while the remaining 15 presented between January and October 1996. The ages of
      the children ranged between 1 and 15 years (Mean 3.0 +/- 4.1 Years). There were
      12 males and 11 females (M:F = 1:1). Sixteen (69.6 percent) out of the 23
      patients were aged between 1 month and 2 years. Sixteen (69.6%) of the 23
      patients acquired the infection vertically, 2 (8.9%) acquired the infection
      through blood transfusion, 1 (4.3%) from sexual abuse, while in 4 (17.4%) the
      source of infection could not be established due to inadequate data. Majority of
      the children presented with weight loss, chronic diarrhoea and fever, while the
      common findings included wasting, oralthrush, pallor, hepatosplenomegaly and
      lymphadenopathy. Six (26.1 percent) out of the 23 children died, 8 (34.8 percent)
      were discharged against medical advice and have not been seen since, 9 (39.1%)
      improved and were discharged to out-patient clinic followup, but all except 2 of
      these have been lost to follow-up. It is concluded that AIDS is increasingly
      becoming a major cause of childhood morbidity and mortality in our environment.
      All children in our environment who present with features of malnutrition should
      be screened for AIDS. Campaigns aimed at preventing vertical (maternal-child)
      transmission, including health education of young men and women on the risk of
      unprotected sex must be vigorously pursued and sustained.

PMID- 9921096
TI  - Radiological diagnosis and management of diverticulitis.
AB  - Thirteen (13) patients with proven diverticulitis are presented with the aim of
      demonstrating the current evaluation and management. Radiological evaluation were
      obtained with plain abdominal x-rays and computed tomography (CT) in all cases,
      abdominal ultrasonography (US) in 8 cases and contrast enema in 5 patients.
      Radiological percutaneous abscess drainage (PAD) were performed in 5 cases, two
      of which preceded surgery. A clinical suspicion of diverticulitis was made in
      only 3 of the 13 cases. CT provided the diagnosis in all cases and helped in
      directing the appropriate management. Ultrasound was also useful but to a lesser
      extent. CT or US guided PAD reduced the surgical operation to a single stage
      procedure instead of the former 2- to 3-stage surgical management. Plain
      abdominal x-ray were only useful for the diagnosis in intestinal obstruction and
      vesical fistula. Contrast enema provided supporting information when necessary.
      CT clearly diagnosed both suspected and totally unsuspected cases of
      diverticulitis and provides guidance for the appropriate management. When CT is
      unavailable US with accurate colonic imaging and abscesses identification can
      also be useful in diagnosing and guiding drainage. Plain abdominal x-rays are
      less helpful but mandatory since the presentation is usually that of acute
      abdomen. Water soluble contrast enema also provides supportive features when
      necessary. In areas where diverticular disease is uncommon, diverticulitis should
      be suspected in cases with left iliac fossa or pelvic pain with mass and
      tenderness.

PMID- 9921097
TI  - Risk of thromboembolism in surgery: myth or reality?

PMID- 9921098
TI  - Retinoblastoma in an adult: a case report.
AB  - A case of retinoblastoma in an adult with a family history of retinoblatoma is
      presented. To our knowledge, this is presumably the first case of retinoblastoma
      recorded in an adult in Northern Nigeria. The differential diagnosis, genetics,
      and importance of counselling and early presentation are discussed.

PMID- 9921099
TI  - Multiple primary carcinomas of the gastrointestinal tract.
AB  - A case of multiple primary Carcinomas of the gastrointestinal tract is reported
      in a man presenting with Carcinomas of the rectum and oesophagus.

PMID- 9921100
TI  - Orbitocephalic metastases from neuroblastoma: report on three cases.
AB  - Three unusual cases of Neuroblastoma with metastasis to the skull and orbit are
      presented. The bizarre clinical features which make diagnosis and subsequent
      management difficult are highlighted, suggesting the need for a multi
      disciplinary approach.

PMID- 9921101
TI  - Subglottic stenosis in a child: a complication of prolonged endotracheal
      intubation.
AB  - A 1 1/2 year old Nigerian child sustained traumatic rupture of the diaphragm
      which was repaired under endotracheal anaesthesia. A red rubber endotracheal tube
      was used for the surgery and a nasotracheal tube was let in situ for 4 days. A
      post intubation subglottic stenosis which developed was managed with a
      tracheostomy and a series of 8 tracheal dilatations under hatothane within a
      period of 5 months. Appropriate choice of tubes and attention to details of
      humidification may have prevented this serious complication.

PMID- 9921102
TI  - [Psychological aspects of tension type headache].
AB  - In understanding and treatment of tension type headache the psychological stress
      is considered as one of the most important factors causing and strengthening
      headache. The aim of this work was the assessment of personality traits in
      patients suffering from tension-type headache. Methods of this study were based
      on investigation of the dimensions of personality using the Eysenck Personality
      Inventory EPQ-R and the assessment of psychological stress using a Questionnaire
      of Demographic Variables. The group of 120 patients suffering from tension-type
      headache was assessed and 30 control subjects without headaches were
      investigated. Special personality traits conditioning/characterising tension-type
      headache were not confirmed. Patients with tension-type headache comparing to
      subjects from the control group showed neurotism and introversion.

PMID- 9921103
TI  - [Time and conditions of cerebral ischemic symptoms appearing during carotid
      endarterectomy under local anesthesia].
AB  - In the 1994-1997 238 carotid endarterectomies (CEA) were performed under regional
      anaesthesia (cervical block) for carotid artery stenosis. In 30 CEA indwelling
      shunt was necessary. Among 30 patients with shunt 19 (63%) had a stroke before
      surgery, then 9 (30%) had contralateral internal carotid artery occlusion. Among
      entire group of 238 patients with CEA 56 (23.5%) had a stroke before surgery and
      27 (11.4%) contralateral internal carotid artery occlusion. In our opinion the
      strongest factor influencing neurological deficiency after clamping trial, is a
      history of stroke before surgery and in a less degree contralateral internal
      carotid artery occlusion. The mean time of the neurological deficit during
      clamping trial was 27 seconds and varied from 5 to 100 sec. and never appeared
      after 2 minutes of mentioned trial. For that reason we consider 2 minutes
      clamping trial as sufficient for detection of neurological deficit during CEA
      under local anaesthesia.

PMID- 9921104
TI  - [Anticardiolopin antibodies as a risk factor in stroke].
AB  - The level of anticardiolipin antibodies (aCL) in sera of 53 patients with
      ischemic cerebrovascular disease aged 35-55 years with mean age 48.4 +/- 5.03,
      was studied using a solid phase enzyme immunosorbent assay (ELISA). The
      investigation was done half year after the ischemic stroke. The control group
      consisted of 21 healthy participants matched for age and sex. The presence of aCL
      was found in sera of 17 persons (32.1%), in 9 it was IgG class antibodies. It was
      indicated that the risk of repeated cerebral ischemic events was relatively
      higher in aCL positive patients than in aCL negative. Relapses were found in 6
      aCL positive patients (35.3%) (in 5 cases from the group of 9 IgG positive) and
      in 2 persons (5.6%) aCL negative patients. The existence of aCL can be helpful to
      determine pathogenesis of the disease and its prognosis.

PMID- 9921105
TI  - [Conservative treatment of trochanteric fractures in the elderly].
AB  - Treatment of trochanteric fractures, especially in patients who are advanced in
      age, presents numerous difficulties; the results of treatment are not always
      satisfactory. The aim of the study was to analyse the results of conservative
      treatment of trochanteric fractures in 50 patients (31 females and 19 males, 65
      94 years of age), who were not qualified for surgery because of sclerosis,
      cerebral haemorrhage in the past, labile diabetes, senile dementia, an advanced
      neoplastic disease, circulatory and respiratory insufficiency, or refusal of
      agreement to the surgery. An adhesion of fracture was obtained in 43 cases (86%).
      28 patients (56%) could move with no difficulties and did not suffer from any
      pain. 7 patients (14%) died (including 2 cases of neoplasm).

PMID- 9921106
TI  - [Antiarrhythmic properties of angiotensin converting enzyme inhibitors].
AB  - In animal experimental models angiotensin converting enzyme (ACE) inhibitors have
      been found to reduce arrhythmias. In patients with cardiovascular disorders
      treated with ACE inhibitors the reduction of incidence and the severity of
      arrhythmias as well as the decrease mortality have been observed. There is little
      evidence to prove that ACE inhibitors affect directly the electrophysiological
      function of a heart. It seems that antiarrhythmic effects of ACE inhibitors are
      indirect.

PMID- 9921107
TI  - [Brain stem auditory evoked potentials in neurological diagnosis].
AB  - In the presented work brainstem auditory evoked potentials were assessed as
      noninvasive nonclinical tests in diagnosis of neurological diseases. The most
      often disorders in particular parts of the recording were also considered. The
      use of brainstem auditory evoked potentials in diagnosis of multiple sclerosis,
      polyneuropathy, vessel disorders, brain traumas, inflammatory and sclerotic
      processes was evaluated.

PMID- 9921108
TI  - [Insulin sensitivity in NIDDM patients with normo- and microalbuminuria].
AB  - There is contradictory information relating to insulin sensitivity in NIDDM
      patients with microalbuminuria. The numerous clinical and epidemiological
      investigations have revealed a greater insulin resistance in these patients.
      However on the ground of the Nielsen and co-workers observations it has been
      ascertained that the level of insulin sensitivity is similar in exactly selected
      NIDDM patients with normo- and microalbuminuria. It suggests, that the increased
      cardiovascular morbidity and mortality among microalbuminuric NIDDM patients may
      not primarily be a consequence of more pronounced levels of hyperinsulinemia or
      insulin resistance. The influence of environmental factors may aggravate resident
      insulin resistance, elevate albuminuria, and may cause itself an increased
      cardiovascular risk.

PMID- 9921109
TI  - [Atypical way of treatment of cardiac stab wounds].
AB  - The paper presents a case of thoracic wall stab wound with profound bleeding
      masking simultaneous cardiac wound successfully sutured through unusual approach.

PMID- 9921110
TI  - [Angiographic findings in hereditary hemorrhagic teleangiectasia: a case study of
      Rendu-Osler-Weber disease].
AB  - A case of Rendu-Osler-Weber disease in 48 year old male was described. Selective
      arteriography of superior mesenteric artery revealed its widening (including
      intestine branches), numerous anastomoses in the form of microhaemangioma and
      fast venous return with broad superior mesenteric and portal vein.

PMID- 9921111
TI  - [Acute superior vena cava syndrome caused by benign goiter].
AB  - The authors present a patient at old age with acute superior caval vein syndrome
      caused by a large benign goitre. Surgical treatment gave a very good early result
      and a very good late one, inspite of numerous additional burdens subsequent to
      biological condition of the operated patient.

PMID- 9921113
TI  - [The infection of the vascular prosthesis treated by the human cryopreserved
      allograft implantation: a case report].
AB  - 75 years old patient was admitted to the Department with infection of the
      previously implanted bifurcated aorto-bifemoral by-pass. Periprosthetic
      retroperitoneal abdominal abscess in the US--colour doppler examination was
      recognized. Unilateral femoral pulse was present--the patient after femoral
      amputation of the right leg. In the first step of the treatment, the drainage of
      the periprosthetic abscess was performed. Because of poor results of the local
      and pharmacological treatment and bleeding from the prosthesis, in the next step,
      human cryopreserved aorto--femoral allograft was implanted "in situ".
      Simultaneously, bifurcated prosthesis was evacuated. In the postoperative period,
      healing of the inquinal wounds was excellent. There were no problems connected
      with peripheral circulation. The patient was discharged from the hospital on the
      24th post-operative day in the good local and general condition. Homograft is an
      efficient and promising alternative for the treatment of severe vascular
      prosthesis infections.

PMID- 9921112
TI  - [A large lipoma].
AB  - The paper presents a female with lipoma of a such magnitude that its size and
      localization rendered impossible walking without assistance.

PMID- 9921114
TI  - Influence of a carrier and basis upon liberation of chlorpropamide from rectal
      suppositories with an active substance in the dispersion system.
AB  - Twelve series of rectal suppositories with chlorpropamide in two dispersion
      systems, containing different quantities of active substance and urea, were
      prepared upon lipophilic and hydrophilic bases. Liberation of chlorpropamide from
      suppositories was examined by the dialysis method. It was found out that the
      process of chlorpropamide liberation from the suppositories depends on the
      quantity of the carrier included in the dispersion systems and on the type of the
      medium used.

PMID- 9921115
TI  - 2-Mercapto-N-(azolyl)benzenesulfonamides. V. Syntheses, anti-HIV and anticancer
      activity of some 4-chloro-2-mercapto-5-methyl-N-(1,2,4- triazolo[4,3-a]pyrid-3
      yl)benzenesulfonamides.
AB  - A series of 4-chloro-2-mercapto-5-methyl-N- (1,2,4-triazolo[4,3-a]pyrid-3-yl)
      benzenesulfonamides [IIIa-IIId] was obtained by the reaction of 6-chloro-7-methyl
      3-methylthio- 1,4,2-benzodithiazine 1,1-dioxide with some 2-hydrazinopyridines.
      Preliminary screening data indicated that compounds [IIIa-IIId] exibited moderate
      or fairly high anti-HIV activity and moderate anticancer activity.

PMID- 9921116
TI  - Glycine derivatives of imidazolones as potential ligands of glycine binding site
      of NMDA receptors. Part 1.
AB  - The series of glycine derivatives of diphenyl or (un)substituted arylidene
      imidazolones was designed and obtained as potential ligands of the glycine
      binding site of NMDA receptors. The compounds were evaluated in vitro for their
      affinity to the glycine binding site of NMDA receptors using as radioligand [3H]
      L-689,560. Their anticonvulsant activity was estimated in vivo in maximal
      electroshock seizure (MES) and subcutaneous pentylenetetrazole (scMet) tests. To
      explain the structure, pharmacological activity results Multiple Linear
      Regression Analysis was used.

PMID- 9921119
TI  - Biomimetic sensor for protein toxins.

PMID- 9921117
TI  - Structure and activity studies on glycine receptor ligands. Part 5. Diphenyl
      imidazolin-4-one glycinamides.
AB  - A series of glycinamides, derivatives of diphenyl imidazolon-4-one was designed
      and obtained as potential ligands of the glycine binding site of NMDA receptors.
      The compounds were evaluated in vitro for their affinity for the glycine binding
      site of NMDA receptors using [3H]-L-689,560 as radioligand. Their anticonvulsant
      activity was estimated in vivo in a maximal electroshock seizure (MES) and
      subcutaneous pentylenetetrazole (scMet) tests. The volume and the surface of the
      molecules seem to be important in elucidating the relation between the structure
      and the pharmacological properties.

PMID- 9921118
TI  - Synthesis of new derivatives of 4-methyl-5-ethoxalyl-1H-2,3,4,5- tetrahydro-1,5
      benzodiazepin-2-one and their psychotropic and anti-proliferative activities.
AB  - 5-Ethoxalyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin -2-one [I] was
      treated with some selected secondary amines (dimethyl-, diethyl-, dipropyl-,
      disobutylamine or with morpholine) and methyl-hydrazine. Amides II-IV and
      hydrazide VII were obtained. Compounds II, IV and VI were tested for their
      psychotropic activity; they showed a weak toxicity. Compounds II and VI showed an
      anxiolytic activity. Compounds I, II, IV, VI and VII were screened for their
      cytotoxic (anti-proliferative) activity in vitro by using different human cancer
      cell lines. None of them revealed any inhibiting effect against the tumor lines
      used.

PMID- 9921120
TI  - Near-field scanning optical microscopy.

PMID- 9921121
TI  - Capillary array electrophoresis DNA sequencing.

PMID- 9921122
TI  - Analysis of human skin emanations by gas chromatography/mass spectrometry. 1.
      Thermal desorption of attractants for the yellow fever mosquito (Aedes aegypti)
      from handled glass beads.
AB  - Handled glass has the ability to collect and concentrate nonaqueous human skin
      emanations while minimizing the collection of aqueous perspiration. Compounds
      originating from the skin and collected on glass have previously been found to
      attract the Aedes aegypti species of mosquito. Therefore, glass beads were used
      as the medium to collect skin emanations from humans for subsequent chemical
      analysis. This process consisted of a 5-15-min collection of sample on glass
      beads, followed by loading the beads into a gas chromatograph (GC) injector
      insert for subsequent desorption of the collected compounds onto the GC column.
      After cryofocusing by liquid nitrogen at the head of the column, the thermally
      desorbed compounds were analyzed by GC/MS. Microscale purge and trap introduction
      was also used to provide complementary information. In this case, the beads are
      held in a round-bottom flask, purged with nitrogen, and heated as the
      concentrator collects the headspace above the beads. The chromatograms produced
      by both of these sample introduction methods demonstrate good resolution of a
      complex sample. Cryofocusing volatiles from handled glass allowed identification
      of lactic acid, aliphatic fatty acids, and other polar to nonpolar compounds of
      moderate volatility while purge and trap allowed detection of nonpolar to
      moderately polar compounds of high volatility.

PMID- 9921123
TI  - Automated frit inlet/frit outlet flow field-flow fractionation for protein
      characterization with emphasis on polymeric wheat proteins.
AB  - A flow field-flow fractionation (FFF) unit fitted with a 254-nm spacer, frit
      inlet (FI), and frit outlet (FO) was automated for protein analysis by addition
      of a system controller, autosampler, and computer software to control pumps,
      sample loading, and data capture. Standard molecular size marker proteins and
      polymeric wheat storage protein extracts were used to assess the performance of
      the automated unit. Optimum resolution for these proteins was obtained with a
      sample inlet flow of 0.2 mL/min, a frit inlet flow (recirculating) of 1.4 mL/min,
      and a cross-flow (recirculating) of 5 mL/min using 0.05 M acetic acid containing
      0.002% FL-70 as a carrier. Use of the FIFO FFF eliminates the requirement for
      stop-flow relaxation and pressure balancing, results in better reproducibility,
      and generates a 7-10-fold increase in sensitivity at the detector by
      concentrating fractions eluting from the channel. These improvements resulted in
      superior resolution of polymeric wheat protein fractions compared to those
      obtained previously using a standard channel with manual load and stop-flow
      relaxation, allowing accurate integration of peak or size range areas. Automation
      of this system allows unattended sample fractionation and hence markedly
      increases potential for sample throughput.

PMID- 9921124
TI  - Monitoring cellular release with dynamic channel electrophoresis.
AB  - A channel electrophoresis system consisting of a 50 microns by 75 mm by 25 mm
      separation channel has been adapted to follow stimulated release from individual
      and small groups of isolated neurons. The cells of interest are placed in a
      nanoperfusion chamber located near the exit of a sampling capillary. The
      capillary is scanned across the mouth of the channel so that compounds released
      from the cells are dynamically introduced into the separation channel. The
      position of the sampling capillary along the channel entrance yields temporal
      information, and electrophoresis in the channel length dimension provides the
      chemical data. NDA/CN- is placed in the inlet vial between the sampling capillary
      and channel so that primary amine-containing compounds released from the cell are
      derivatized prior to separation as they enter the channel. The performance of
      this method is evaluated, and the optimum NDA/CN- concentration and separation
      conditions for this on-line derivatization are presented, with detection limits
      for most underivatized amino acids of approximately 500 nM at a particular time
      slice. The time-resolved electropherograms from single and a small group of
      cerebral ganglion neurons from Aplysia californica stimulated with KCl show
      multiple components released with different time courses.

PMID- 9921125
TI  - Membrane supports as the stationary phase in high-performance immunoaffinity
      chromatography.
AB  - The membrane with a composite of cellulose grafted with acrylic polymers formed
      by polymerizing a glycidyl methacrylate in the presence of dispersed cellulose
      fiber was prepared as the stationary phase; the column (40 x 4 mm i.d.) which was
      compatible with the HPLC instrument was packed with pieces of the cut membrane.
      Protein A and human IgG were immobilized on the membrane stationary phase. The
      column based on the membrane support provided us good reproducibility, high
      efficiency, and low back pressure. High-performance immunoaffinity
      chromatographic analysis of human IgG in serum and polyclonal antibody to human
      IgG raised in goat was performed within 2.5 min. The fast-speed immunoaffinity
      analysis was developed by increasing the flow rate of the mobile phase and
      decreasing the duration time for the switch of the mobile phase; an operation for
      immunoaffinity analysis of human IgG could be finished within 30 s.

PMID- 9921126
TI  - Procedure for analysis of radium in freshwaters by adsorption on basic lead
      rhodizonate.
AB  - Radium analysis is carried out by batch adsorption from natural waters on basic
      lead rhodizonate supported on charcoal, LERHO, starting from 2-L samples. 133Ba
      is added to allow the measurement of the overall chemical yield by gamma
      counting. Radium is recovered with a few milliliters of 1.5 M HCl, and lead is
      removed by a chromatographic column filled with Dowex 2 x 8. Finally 50
      micrograms of barium carrier is added, and the radium is coprecipitated as
      sulfate on a preformed bed of barium sulfate, to prepare a sample suitable for
      alpha and gamma counting. The detection limit of the proposed method is 0.002
      Bq/L 226Ra. This value is far beyond the radium activity admissible for drinking
      waters. Due to lack of appropriate samples, the procedure was tested using
      mineral waters spiked with 226Ra and two commercially available mineral waters
      with very low radium contents.

PMID- 9921127
TI  - Guanidinium-based potentiometric SO2 gas sensor.
AB  - An SO2 gas sensor was developed by using a hydrogen sulfite-selective electrode
      positioned behind a gas-permeable membrane (GPM). The hydrogen sulfite-selective
      electrode was prepared by incorporating a multicyclic guanidinium ionophore in a
      plasticized poly(vinyl chloride) membrane. This gas sensor presents important
      advantages over the conventional Severinghaus-type SO2 gas sensor that contains a
      pH electrode immersed in an internal solution behind the GPM. The Severinghaus
      gas sensor suffers interferences from weak acids that can cross the GPM as gases
      and change the pH of the internal solution. In contrast, in the proposed sensor,
      the excellent selectivity of the HSO3- electrode and the ability of the GPM to
      discriminate gaseous from nongaseous species combine to generate the most
      selective potentiometric SO2 gas sensor reported to date.

PMID- 9921128
TI  - Anion dopant for oligosaccharides in matrix-assisted laser desorption/ionization
      mass spectrometry.
AB  - A new anion dopant for oligosaccharides is developed for use in matrix-assisted
      laser desorption/ionization mass spectrometry. Two types of sulfate-attached
      quasimolecular ions are formed in the negative ion mode when neutral
      oligosaccharides are doped with dilute H2SO4 solutions. Under mild conditions,
      i.e., low H2SO4 concentration (approximately 10(-3) M) and threshold laser
      fluence, a sulfate adduct [M + HSO4]- is formed. With more concentrated H2SO4
      solutions (approximately 10(-2) M) and higher laser fluence, in situ
      derivatization of the oligosaccharides occurs to produce an ion whose m/z
      corresponds to a sulfate derivative [M + HSO4 - H2O]-. Hydrogen sulfate appears
      to be a general anion dopant because it forms complexes with a wide variety of
      neutral oligosaccharides. Conversely, anionic oligosaccharides form neither the
      adduct nor the derivative. The combination of complex formation (with neutral
      oligosaccharides) and the deprotonation of acidic oligosaccharides allows
      simultaneous detection of the respective mixture.

PMID- 9921129
TI  - Tandem-in-time mass spectrometry method for the sub-parts-per-trillion
      determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans in
      high-fat foods.
AB  - Limits of quantitation (LOQs) for a quadrupole ion storage tandem-in-time mass
      spectrometry (QISTMS) method were evaluated through replicate analysis of
      unfortified peanut oil, shortening, lamb fat, and butter for all 2,3,7,8-chlorine
      substituted polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans
      (PCDFs). Ten congeners were measurable in butter (0.27-2.5 pg/g) and nine
      congeners were measurable in lamb fat (0.09-2.6 pg/g) with good precision. LOQs
      for high-fat foods were estimated by triplicate analysis of peanut oil fortified
      at two levels. Accurate and reproducible results were achieved at 0.5 pg/g for
      most PCDD/Fs (1.0 pg/g for heptachlorodibenzo-p-dioxin and
      heptachlorodibenzofuran and 2.0 pg/g for octachlorodibenzofuran) and at 0.2 pg/g
      for 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). QISTMS distinguished between catfish and chicken eggs with
      elevated TCDD levels from background samples collected from the most regions of
      the continental United States. QISTMS determined the extent of TCDD contamination
      in butter, lamb fat, and cottonseed oil collected from rural villages in
      Kazakhstan. Replicate analysis of catfish and chicken eggs by the QISTMS method
      produced comparable results to high-resolution mass spectrometry (HRMS). Lower
      limits of detection will be needed if QISTMS is to fully complement HRMS in the
      measurement of TCDD levels in food.

PMID- 9921130
TI  - Mapping of phosphorylation sites of gel-isolated proteins by nanoelectrospray
      tandem mass spectrometry: potentials and limitations.
AB  - Precursor ion scans have proven to be extremely useful for the characterization
      of unseparated peptide mixtures. In conjunction with the nanoelectrospray source,
      precursor ion scans provide a sensitive tool for the detection of
      posttranslationally modified peptides and have been used to determine
      phosphorylation sites of proteins digested in solution. In this report, we extend
      our previous work to the determination of protein phosphorylation sites of gel
      isolated proteins. The in-gel digestion procedure developed in our laboratory for
      protein microsequencing was found to be suitable for phosphorylation mapping as
      well. The risk of losing hydrophilic peptides in the desalting step was decreased
      by using column packing material designed for the purification of
      oligonucleotides and by adjusting the pH conditions to the needs of
      phosphopeptide analysis. With this method, the tryptic phosphopeptides of beta
      casein were detected after in-gel digestion at a sensitivity of 250 fmol of
      protein applied to the gel. The phosphorylation sites of two other proteins, Src
      delta U and Op18, have similarly been mapped. Subpicomole to low-picomole amounts
      of protein starting material are needed in general, although we and others have
      reported attomole sensitivity for the detection of model phosphopeptides using
      precursor ion scans. This indicates that the success in determining
      phosphorylation sites depends crucially on the digestion, extraction, and
      detection efficiency for individual phosphopeptides.

PMID- 9921131
TI  - HPLC/tandem electrospray mass spectrometry for the determination of Sub-ppb
      levels of Pacific and Caribbean ciguatoxins in crude extracts of fish.
AB  - Ciguatera is a significant food-borne disease caused by potent polyether toxins
      (ciguatoxins) which accumulate in the flesh of ciguateric reef fish at risk
      levels > 0.1 ppb for Pacific ciguatoxins. Research on ciguatera has been severely
      hindered by the lack of analytical methods that detect and characterize low
      levels of ciguatoxin in crude extracts of fish. Here we report a new procedure
      for ciguatoxin analysis based on gradient reversed-phase HPLC/tandem mass
      spectrometry (HPLC/MS/MS). The method gave a linear response to pure Pacific and
      Caribbean ciguatoxins (P-CTX-1 and C-CTX-1) and the structurally related
      brevetoxin (PbTx-2) spiked into crude extracts of fish. Levels equivalent to 40
      ppt P-CTX-1, 100 ppt C-CTX-1, and 200 ppt PbTx-2 in fish flesh could be detected
      by HPLC/MS/MS. Using P-CTX-1 as an internal standard, the analysis of extracts of
      30 ciguateric fish from the Caribbean Sea (8 toxic, 12 borderline, and 10
      nontoxic by mouse bioassay) confirmed the reliability of the method and allowed
      an estimated risk level of > 0.25 ppb C-CTX-1 to be established. HPLC/MS/MS
      provides a sensitive analytical approach, not previously available, for the
      determination of Pacific and Caribbean ciguatoxins at sub-ppb levels in fish
      flesh.

PMID- 9921132
TI  - Tubular-wire dual electrode for detection of thiols and disulfides by capillary
      electrophoresis/electrochemistry.
AB  - A new dual-electrode detector for capillary electrophoresis is described. The
      detector consists of an integrated gold tubular electrode as the generator
      electrode and a gold wire electrode for detection. The detector configuration,
      including electrode size and position, has been optimized in terms of detection
      sensitivity and separation efficiency. After amalgamation of the dual electrode
      with mercury, the capillary electrophoresis/electrochemistry system was employed
      for simultaneous detection of thiols and disulfides. The response of cystine was
      found to be linear from 1 microM to 1 mM with a LOD of 0.5 microM (S/N = 3) and
      sensitivity of 60 pA/microM. The detection limits represent 200-fold improvement
      over previously reported dual-electrode designs for the detection of disulfides.
      The use of this detector for identification of thiol- and disulfide-containing
      peptides was demonstrated with a tryptic digest of ribonuclease A.

PMID- 9921133
TI  - Silicon-29 nuclear magnetic resonance spectroscopy detection limits.
AB  - We show that an unmodified, commercially available high-field (17.61T) NMR
      spectrometer using the DEPT pulse sequence is capable of detecting silicon
      containing species down to concentrations of 150 ng/mL (150 ppb) per spin site.
      This is in the range given for the concentration of silicon in the blood of
      silicone breast implant recipients, as determined by ICP analysis, and
      demonstrates that, contrary to the view expressed in the literature, in theory
      29Si NMR may be sufficiently sensitive to be of use in determining the nature of
      the silicon-containing species present. A summary of the factors affecting the
      detection limits in NMR spectroscopy is given.

PMID- 9921134
TI  - Effects of protein-surface interactions on protein ion signals in MALDI mass
      spectrometry.
AB  - The influence of polymer surface-protein binding affinity on protein ion signals
      in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is
      examined. The surfaces of poly(vinylidene fluoride) and poly(ethylene
      terephthalate) polymer substrates are modified by pulsed rf plasma deposition of
      allylamine. By varying the on/off duty cycle of the pulsed rf plasma, the polymer
      substrate surfaces are coated with thin films having varying densities of surface
      amine groups. The varying surface amine density is shown to lead to systematic
      changes in the surface binding affinity for the 125I-radiolabeled peptides
      angiotensin I and porcine insulin. Unlabeled angiotensin I and porcine insulin
      are then deposited on the pulsed rf plasma-modified substrates and analyzed by
      MALDI mass spectrometry. The experimental approach involves applying the peptide
      to the modified polymer surface in an aqueous phosphate-buffered saline solution
      and allowing the peptide solution to dry completely under ambient conditions.
      Subsequently, the MALDI matrix alpha-cyano-4-hydroxycinnamic acid in methanol and
      10% trifluoroacetic acid in water are added to the peptide-coated modified
      polymer surfaces. The results of these studies demonstrate that, for the sample
      preparation method employed, increases in the surface peptide binding affinity
      lead to decreases in the peptide MALDI ion signal.

PMID- 9921136
TI  - Detection of individual oligonucleotide pairing by single-molecule microscopy.
AB  - Hybridization of 20 mer probe oligonucleotides to complementary, surface
      immobilized target oligonucleotides was visualized on a single-molecule basis by
      fluorescence microscopy. Coincident determination of the positions of both the
      target and the probe oligonucleotides using dual-wavelength fluorescence labeling
      allowed for highly reliable discrimination of specifically bound probe molecules
      from those being physisorbed. The figures of merit of the assay are characterized
      by the low probability for false positive (10(-4)) events and the high speed for
      detection of up to hundreds of different DNA fragments per second. The
      probability for false negative events is limited by the biochemical binding
      probability of short oligonucleotides. The potentials and limitations of this
      methodology for single-cell single-DNA analysis are discussed.

PMID- 9921137
TI  - Polyhydroxybutyrate: plastic made and degraded by microorganisms.
AB  - Polyhydroxybutyrate (PHB) offers many advantages over traditional petrochemically
      derived plastics. In addition to its complete biodegradability, PHB is formed
      from renewable resources. It possesses better physical properties than
      polypropylene for food packaging applications and is completely nontoxic. The
      poor low-impact strength of PHB is solved by incorporation of hydroxyvalerate
      monomers into the polymer to produce polyhydroxybutyrate-co-valerate (PHBV),
      which is commercially marketed under the trade name Biopol. Like PHB, PHBV
      completely degrades into carbon dioxide and water under aerobic conditions.
      Microbial synthesis of PHB is the best method for industrial production because
      it ensures the proper stereochemistry for biodegradation. Microorganisms
      synthesize and store PHB under nutrient-limited conditions and degrade and
      metabolize it when the limitation is removed. Current production employs
      Alcaligenes eutrophus because it grows efficiently on glucose as a carbon source,
      accumulates PHB up to 80% of its dry weight, and is able to synthesize PHBV when
      propionic acid is added to the feedstock. PHBV is currently 16 times the price of
      polypropylene. However, the development of transgenic PHA-producing organisms is
      expected to greatly reduce its cost. Benefits of using transgenic systems include
      lack of a depolymerase system, ability to use faster-growing organisms,
      production of highly purified polymers, and ability to utilize inexpensive carbon
      sources. Because transgenic plants may someday result in the evolution of plastic
      crops that could lower the price of PHA to a competitive level, future research
      will surely focus on such recombinant DNA techniques.

PMID- 9921138
TI  - Lead contamination in Uruguay.
AB  - Uruguay is a developing country of South America with about 3 million people,
      half of whom live in its principal city, Montevideo. This city has several lead
      pollution sources as emitting industries, most of them surrounded by residential
      neighborhoods, some still using lead pipes in drinking water systems of old
      buildings, and has areas of heavy traffic with cars that are still fueled with
      leaded gasoline. The toxic effects of this heavy metal are well known. Children
      are a very sensitive population and their early symptoms of intoxication are not
      always taken into account. Blood lead is a good indicator of recent exposure to
      lead influenced by inhalation and ingestion. The systematic data assessment of
      lead pollution and people exposure in Uruguay was not well known when the
      Department of Toxicology and Environmental Hygiene of the Faculty of Chemistry
      began to analyze lead in biological samples, first from exposed workers and next
      from children and the general population, including sensitive animal species like
      dogs. Several described studies were carried out analyzing for blood lead to
      assess lead uptake and to obtain reference values for Uruguayan populations.
      Since 1986, that Department is the only laboratory where blood lead analyses are
      done, and the analytical method has been controlled by an interlaboratory quality
      control program of the Ministry of Labour of Spain and confirmed by experts from
      the Laboratory of Occupational and Environmental Medicine of Lund, Sweden.
      Financial and technical support was obtained from Sweden (SAREC) and also from
      the University of the Republic of Uruguay. Uruguayan lead workers have always
      been the principally studied population because their lead exposure assessment as
      well as their health protection education is not always done properly. Uruguay
      has adopted ACGIH reference values (150 micrograms/m3 in total lead dust, 50
      micrograms/m3 respirable lead dust, 300 micrograms/L blood), and the high blood
      lead levels indicate significant adverse health risks effects and show a lack
      adequate controls for working conditions. A surveillance of children living in
      the surroundings of lead processing factories and in different neighborhoods was
      conducted because no data were available for blood lead in children before 1992.
      Also, general populations living in those areas or in areas of heavy traffic were
      assessed. Blood lead levels were always compared with those of control
      populations sampled at the same time answering a questionnaire. Workplace
      influence as well as atmospheric, soil, and water pollution were always
      considered to explain the obtained results. Some studies were carried out in dogs
      as a sensitive population, showing their higher exposure. The described studies
      included internal and external quality controls for the analytical methods and
      data processing. All blood lead analyses were done by atomic absorption
      spectrometry (AAS) after adding complexing agent and extraction. Samples taken
      together with Swedish researchers were analyzed in Lund (Department of
      Occupational and Environmental Medicine University Hospital), at 283.3 nm after
      electrothermal atomization (ETA). There was good correlation (r = 0.96) among 28
      samples shared between Montevideo and Lund laboratories. The authors recommend
      more systematic clinical examination of workers, children, and the general
      population to determine the potential health risks for Uruguayan populations so
      as to improve their health conditions and to officially recognize lead pollution
      as an environmental problem.

PMID- 9921139
TI  - Microbial methods for assessing contaminant effects in sediments.
AB  - Contaminated sediments influence drastically the long-term toxicological and
      ecological properties of aquatic ecosystems. During the past three decades,
      scientific knowledge about sediment-water exchange processes and the deposition
      and distribution of pollutants in water and sediment phases has been supplemented
      by extensive research on the effects of sediment-associated pollutants on aquatic
      organisms. Basic research in microbiology, ecology, and toxicology has uncovered
      the crucial role of sediment microorganisms for the biodegradation of organic
      matter and for the cycling of nutrients, as well as the susceptibility of these
      processes to toxic pollution events. Microorganisms have been extensively applied
      in aquatic toxicology, and various microbial toxicity tests are today available
      that successfully couple microbial toxicity endpoints to the specificity of the
      sediment matrix. Sediment-associated toxicants can be brought in contact with
      test bacteria using sediment pore waters, elutriates, extracts, or whole-sediment
      material. Toxicity indication principles for microorganisms are versatile and
      comprise growth and biomass determinations, respiration or oxygen uptake,
      bacterial luminescence, the activity of a variety of enzymes, and a compendium of
      genotoxicity assays. The border between toxicological and ecological contaminant
      effect evaluations in sediments is flexible, and long-term ecological predictions
      should also include an assessment of pollutant degradation capacities and of key
      reactions in element cycling. Evaluating microbial community structure and
      function in environmental systems makes use of modern molecular techniques and
      bioindicators that could trigger a new quality in the assessment of contaminated
      sediments in terms of indication of subtoxic effects and early-warning
      requirements.

PMID- 9921140
TI  - The impact of rice pesticides on the aquatic ecosystems of the Sacramento River
      and Delta (California).
AB  - Since the early 1980s, when molinate was demonstrated to have killed carp in
      agricultural drains, an intensive research effort has been undertaken to assess
      the impact of rice pesticides on aquatic ecosystems in the Sacramento River and
      Delta. No impact has been found that can be clearly attributed to rice
      pesticides. However, the rice insecticides methyl parathion and carbofuran, and
      probably also bufencarb, reached levels in the River and Delta that, based on
      laboratory bioassays, would have been toxic to aquatic microinvertebrates and, in
      the case of bufencarb, to early life stages of striped bass. Reductions in
      microinvertebrate populations could have impacted higher organisms in the aquatic
      food chain such as striped bass and chinook salmon. Bufencarb was not used after
      1981. Since then, changes in the management of the remaining rice pesticides have
      resulted in dramatic decreases in the levels of these chemicals in the River and
      Delta. Levels achieved today have no known toxicity to aquatic organisms. As
      releases of rice pesticides were reduced to achieve nontoxic levels in the River
      and Delta, however, commensurate recoveries of striped bass and chinook salmon
      did not occur, suggesting that rice pesticides may have had little or no role in
      the decline of these species.

PMID- 9921141
TI  - Childhood brain tumors and residential electromagnetic fields (EMF).
AB  - There are many recent comprehensive reviews of the residential EMF epidemiologic
      literature, but they do not attempt to cover the issue of childhood brain tumors
      and EMF in depth. We present here background information on descriptive
      epidemiology of known or suspected causes of childhood brain tumors and a
      detailed review of studies that have examined the associations between EMF as
      represented by various surrogates, and childhood brain tumors. We evaluated nine
      studies of childhood brain tumors and residential exposure to EMF based on wire
      codes, distance, measurements, and modeling, and six studies that examined the
      use of appliances by children or their mothers during pregnancy. For each study
      we discussed analytical and methodological issues including choice of cutpoints,
      nonconcurrent control selection, random digit dialing, differential
      participation, and ability of a study to detect an association. On the basis of
      this comprehensive review of all available childhood brain cancer studies, we do
      not see support for an overall association between EMF and childhood brain
      cancer. This lack of support applied for all surrogates of past magnetic fields,
      including wire code, distance, measured or calculated fields, and use of
      appliances by either child or mother.

PMID- 9921142
TI  - Telling the story of quality: the use of storyboards in nursing units.

PMID- 9921143
TI  - Conversation. The strength of the Nursing Work Force Development in New Mexico.

PMID- 9921144
TI  - Review of magnet hospital research: findings and implications for professional
      nursing practice.
AB  - The label "magnet hospitals" originally was given to a group of U.S. hospitals
      that were able to successfully recruit and retain professional nurses during a
      national nursing shortage in the early 1980s. Studies of magnet hospitals
      illuminated the leadership characteristics and professional practice attributes
      of nurses within these organizations. Recent investigations within magnet
      hospitals document significant relationships between nursing and patient
      outcomes, including mortality and patient satisfaction. The purpose of this
      review is to: 1) synthesize the magnet hospital research that describes and
      evaluates the professional practice of nurses within these institutions and (2)
      identify areas for future research to advance professional nursing models within
      current hospital organizations.

PMID- 9921145
TI  - Establishing a research coordinator network: the birth of an idea.
AB  - Located throughout academic institutions, private hospitals, and clinic settings,
      clinical research nurse coordinators often practice outside the purview of
      institutional nursing departments yet must adhere to established nursing practice
      standards. Nursing administrators have a professional and legal responsibility to
      recognize the educational needs and competency requirements of these individuals
      and provide them with tools for their professional development. Establishing a
      network for clinical research nurse coordinators provides a forum for education,
      problem-solving, benchmarking performance, and camaraderie.

PMID- 9921146
TI  - Recognition of staff nurse job performance and achievements: staff and manager
      perceptions.
AB  - Recognition for job performance is central to staff nurse morale. However, little
      research has been done to identify recognition methods most valued by nurses
      themselves. The authors report results of a multisite survey conducted to compare
      staff and manager perceptions of meaningful recognition behaviors. They provide
      data for developing management interventions that may help to improve morale and
      increase retention. Given the financial constraints of the current environment,
      the nonmonetary recognition practices identified are of particular significance.

PMID- 9921147
TI  - Organizational factors, nurses' job satisfaction, and patient satisfaction with
      nursing care.
AB  - For this research study, the authors explored differences and relationships among
      the job satisfaction of registered nurses, patient satisfaction with nursing
      care, nursing care delivery models, organizational structure, and organizational
      culture. There were no differences in nurses job satisfaction or patient
      satisfaction with nursing care in different organizational structures or where
      different nursing care delivery models were used. A supportive environment was
      most important to the job satisfaction of nurses.

PMID- 9921148
TI  - Patient needs in the emergency department: nurses' and patients' perceptions.
AB  - Patients arrive at emergency departments in distress. Physical needs are
      addressed, but less pressing emotional and social needs often go unrecognized.
      Although patients may not articulate their concerns, they may later feel
      dissatisfaction if needs were unmet. This study determined whether emergency
      department patients and nurses have similar perceptions of patients' needs, and
      which needs patients identify as most important. A convenience sample of patients
      and nurses in a two-hospital system was selected. Study results indicate that
      nurses may not always perceive accurately patients' needs or the strength of
      those needs. Institutions that place a high value on patient satisfaction with
      care must treat patient-centeredness as a priority--at all institutional levels.

PMID- 9921149
TI  - Improving productivity: a payer/provider debate.
AB  - In the world of healthcare, there is a great deal of passion about productivity.
      Even mention of the word sparks internal angst and intense discussion--among
      providers and payers alike. Creating dialogue about productivity and its merits
      was the motivating force behind a debate at the American Organization of Nurse
      Executives 31st Annual Meeting in San Diego, California. Payer and provider
      representatives were given an opportunity to define and elaborate key factors
      that drive or inhibit productivity and core issues related to an important
      coexisting variable, that is, quality. The debate was moderated by Ann Van Slyck,
      MSN, RN, CNAA, FAAN, President of Van Slyck & Associates, Inc., of Phoenix,
      Arizona.

PMID- 9921150
TI  - Management forecast: optimizing the use of organizational and individual
      knowledge.
AB  - Knowledge management provides a means for sharing data, lessons learned, and
      accumulated knowledge throughout an organization or within an entire industry.
      Gone are the days of hoarding knowledge to ensure job security; today's workers
      and managers must work together to find new and innovative ways to use what they
      know and optimize how that knowledge is accessed. Knowledge management's new
      approach to shared intellectual resources has implications for workers and
      managers in all fields and promises to redraw the management landscape. But are
      healthcare organizations setting the stage for reengineering themselves all over
      again?

PMID- 9921151
TI  - Metabolite and isotopomer balancing in the analysis of metabolic cycles: II.
      Applications.
AB  - In a previous paper (Klapa et al., 1999), we presented a model for the analysis
      of isotopomer distributions of the TCA cycle intermediates resulting from 13C (or
      14C) labeling experiments. Results allow the rigorous determination of the degree
      of enrichment at specific carbon atoms of metabolites, of the molecular weight
      distribution of metabolite isotopomers, as well as of the fine structure of NMR
      spectra in terms of a small number of metabolic fluxes. In this paper we validate
      the model by comparing model predictions with experimental data and then apply it
      to the analysis of metabolic networks that have been investigated in previous
      studies. The results have allowed us to conclude that: (1) there is no evidence
      of propionyl-CoA carboxylase pathway in Escherichia coli; and (2) the possibility
      that acetone utilization in mammals occurs solely via the "lactate/methylglyoxal"
      pathway is consistent with available labeling data. The presented modeling
      framework provides additional constraints that must be satisfied by experimental
      data in a biochemical network structure and therefore enhances the power of
      labeling methods for resolving in vivo metabolic fluxes.

PMID- 9921153
TI  - Influence of furfural on anaerobic glycolytic kinetics of Saccharomyces
      cerevisiae in batch culture.
AB  - Furfural was reduced to furfuryl alcohol by Saccaromyces cerevisiae with a yield
      of 0.97 +/- 0.01 mmol/ mmol causing a lag phase in cell growth. In the presence
      of 29 mM, furfural the cell-mass yield on glucose decreased from 11.0 +/- 0.1
      mg/mmol (0.06 +/- 0.0006 g/g) in a reference fermentation without furfural to 9.7
      +/- 0.07 mg/ mmol (0.05 +/- 0.0004 g/g), whereas the ethanol yield on glucose
      increased from 1.6 +/- 0.03 to 1.7 +/- 0.03 mmol/mmol. No glycerol was excreted
      during furfural reduction, and the lag phase in acetate production was extended
      from 1 h in the reference fermentation to 5 h in the presence of furfural.
      Acetaldehyde and pyruvate were excreted during the furfural reduction phase. Cell
      growth and cell maintenance were proportional to glucose consumption during the
      entire fermentation, whereas the cell-mass yield on ATP produced was low during
      furfural reduction. These observations indicate that furfural addition to a batch
      culture decreased cell replication without inhibiting cell activity (designated
      as replicative inactivation). The absence of glycerol production during furfural
      reduction suggests that furfural acted as an alternative redox sink oxidizing
      excess NADH formed in biosynthesis. A mechanistic mathematical model was
      developed that described accurately the fermentation in the absence and presence
      of furfural. The model was based on the assumptions that: (i) furfural reduction
      to furfuryl alcohol by NADH-dependent dehydrogenases had a higher priority than
      reduction of dihydroxyacetone phosphate to glycerol; and (ii) furfural caused
      inactivation of cell replication. The effect of furfural on cell replication is
      discussed in relation to acetaldehyde formation. Inactivation of cell replication
      was modeled by considering two populations within the cell culture, both
      metabolically active, but only one replicating. The kinetic description was
      developed as a tool to estimate transient fluxes of carbon, NADH/NAD+ and
      ATP/ADP.

PMID- 9921154
TI  - Chemical treatment of Escherichia coli: 3. Selective extraction of a recombinant
      protein from cytoplasmic inclusion bodies in intact cells.
AB  - In previous parts of this study we developed procedures for the high-efficiency
      chemical extraction of soluble and insoluble protein from intact Escherichia coli
      cells. Although high yields were obtained, extraction of recombinant protein
      directly from cytoplasmic inclusion bodies led to low product purity due to
      coextraction of soluble contaminants. In this work, a two-stage procedure for the
      selective extraction of recombinant protein at high efficiency and high purity is
      reported. In the first stage, inclusion-body stability is promoted by the
      addition of 15 mM 2-hydroxyethyldisulfide (2-HEDS), also known as oxidized beta
      mercaptoethanol, to the permeabilization buffer (6 M urea + 3 mM
      ethylenediaminetetraacetate [EDTA]). 2-HEDS is an oxidizing agent believed to
      promote disulfide bond formation, rendering the inclusion body resistant to
      solubilization in 6 M urea. Contaminating proteins are separated from the
      inclusion-body fraction by centrifugation. In the second stage, disulfide bonds
      are readily eliminated by including reducing agent (20 mM dithiothreitol [DTT])
      into the permeabilization buffer. Extraction using this selective two-stage
      process yielded an 81% (w/w) recovery of the recombinant protein Long-R3-IGF-I
      from inclusion bodies located in the cytoplasm of intact E. coli, at a purity of
      46% (w/w). This was comparable to that achieved by conventional extraction
      (mechanical disruption followed by centrifugation and solubilization). A pilot
      scale procedure was also demonstrated using a stirred reactor and diafiltration.
      This is the first reported study that achieves both high extraction efficiency
      and selectivity by the chemical treatment of cytoplasmic inclusion bodies in
      intact bacterial cells.

PMID- 9921155
TI  - Cultures of cells from fetal rat brain: methods to control composition,
      morphology, and biochemical activity.
AB  - Fetal tissue transplantation is a promising new approach for the treatment of
      neurodegenerative diseases, but the optimal conditions for preparing cells for
      transplantation have not been defined. The growth of a population of septal brain
      cells, primarily containing cholinergic neurons and glia, was characterized after
      seeding at densities from 5 x 10(4) to 6 x 10(5) cells/cm2, on polystyrene-,
      collagen-, laminin-, and fibronectin-coated surfaces, in the presence of serum
      and/or serum-free medium. Differentiated glial cells were selected by culture on
      fibronectin or laminin surfaces, in the presence of low amounts of serum (2.5%
      FBS) and G5, a soluble factor containing EGF and insulin. Differentiated neuronal
      cells were selected by culture on laminin, in the presence of low amounts of
      serum (2.5% FBS) and N2, a soluble factor containing supplemental hormones. In
      each case, a minimum seeding density of 1 x 10(5) cells/cm2 was required.
      Neuronal growth could be maintained long term (21 days) with high levels of
      neuronal activity (ChAT activity).

PMID- 9921157
TI  - Variant antibody identification by peptide mapping.
AB  - During development of CGP56901, a monoclonal antibody (MAb) specific for a unique
      epitope on human IgE, the protein A-purified IgG from one of the candidate
      production cell lines, showed an additional minor heavy chain (H-chain) band with
      a molecular weight slightly lower than that of the principal H-chain band on SDS
      PAGE. The N-terminal amino acid sequence of this minor H-chain species indicated
      that at least the first 30 amino acids were identical to those of the antibody
      light-chain (L-chain) variable domain. More detailed studies using peptide
      mapping and amino acid sequencing analysis confirmed a crossover event between
      the V genes of the antibody. The position is between Arg108 of the L chain and
      Ala124 of the H chain. This crossover resulted in a variant H chain, which had 16
      fewer amino acid residues than the normal CGP56901 H chain. These results show
      that peptide mapping is a useful "first-line" analytical tool in the
      characterization of the quality of the monoclonal antibody.

PMID- 9921156
TI  - Cell death from bursting bubbles: role of cell attachment to rising bubbles in
      sparged reactors.
AB  - Bursting bubbles are thought to be the dominant cause of cell death in sparged
      animal or insect cell cultures. Cells that die during the bubble burst can come
      from three sources: cells suspended near the bubble; cells trapped in the bubble
      lamella; and cells that attached to the rising bubble. This article examines cell
      attachment to rising bubbles using a model in which cell attachment depends on
      cell radius, bubble radius, and cell-bubble attachment time. For bubble columns
      over 1 m in height and without protective additives, the model predicts
      significant attachment for 0.5- to 3-mm radius bubbles, but no significant
      attachment in the presence of protective additives. For bubble columns over 10 cm
      in height, and without protective additives, the model predicts significant
      attachment for 50- to 100-micron radius bubbles, but not all protective additives
      prevent attachment for these bubbles. The model is consistent with three sets of
      published data and with our experimental results. Using hybridoma cells, serum
      free medium with antifoam, and 1.60 +/- 0.05 mm (standard error) radius bubbles,
      we measured death rates consistent with cell attachment to rising bubbles, as
      predicted by the model. With 1.40 +/- 0.05 mm (SE) radius bubbles and either 0.1%
      w/v Pluronic-F68 or 0.1% w/v methylcellulose added to the medium, we measured
      death rates consistent with no significant cell attachment to rising bubbles, as
      predicted by the model.

PMID- 9921158
TI  - [Anesthesiology as a specialty and harmony with its environ].

PMID- 9921159
TI  - [Scientific study of sleep--molecular mechanism for the regulation of sleep and
      wakefulness].

PMID- 9921160
TI  - [Effects of surgery during the neonatal stage on mental and intellectual
      development].

PMID- 9921161
TI  - [Cerebral protection and update on hypothermic therapy].

PMID- 9921162
TI  - [Fundamentals and clinical application of near-infrared spectrophotometry--with
      special reference to cytochrome oxidase].

PMID- 9921163
TI  - [Current topics on hyperbaric oxygenation therapy--application of hyperbaric
      oxygenation to multiple organ failure].

PMID- 9921164
TI  - [Methods for sedation in dental anesthesia].

PMID- 9921165
TI  - [The third space].

PMID- 9921166
TI  - [Stress steroids].

PMID- 9921167
TI  - [Necrosis and apoptosis].

PMID- 9921168
TI  - [Supranormal oxygen delivery].

PMID- 9921169
TI  - [Down regulation].

PMID- 9921170
TI  - [Remifentanil, a new opioid analgesic].

PMID- 9921171
TI  - [Pulse dye-densitometry].

PMID- 9921172
TI  - [Ropivacaine, a new local anesthetic].

PMID- 9921174
TI  - [Current status and future of three-dimensional echocardiography].

PMID- 9921173
TI  - [New muscle relaxants].

PMID- 9921175
TI  - [Landiolol hydrochloride, a new sympathetic beta blocker].

PMID- 9921176
TI  - [Monitoring the anesthetic depth--with special reference to bispectral index].

PMID- 9921177
TI  - [Position of internal medicine in the preoperative evaluation of circulatory
      functions].

PMID- 9921178
TI  - [Evaluation criteria in anesthesiology--with special reference to ischemic heart
      disease].

PMID- 9921179
TI  - [The role of intraoperative echocardiography in surgery of the heart and large
      vessels].

PMID- 9921180
TI  - [Approach to encourage more frequent use of intraoperative echocardiography].

PMID- 9921181
TI  - [Intraoperative fluid infusion in relation to postoperative course--in surgical
      cases of esophageal cancer].

PMID- 9921182
TI  - [Fluid balance and intraoperative care--in surgery of esophageal cancer].

PMID- 9921183
TI  - [Problems related to anesthesiology education and their solutions in the United
      States].

PMID- 9921184
TI  - Anesthesia specialty training in Korea.

PMID- 9921185
TI  - [Effective presentation of an academic study].

PMID- 9921186
TI  - Writing for the British Journal of Anaesthesia--an editor's thoughts.

PMID- 9921187
TI  - [The use of anesthesia-related drugs that are not in the officially approved
      lists covered by the Health Insurance].

PMID- 9921188
TI  - [Legal consideration on the use of drugs outside the Government specification or
      the regulations set by health insurance systems].

PMID- 9921189
TI  - [Pain control mechanism involving opioid receptors].

PMID- 9921190
TI  - [Changes in excitability of the spinal cord and dorsal column nucleus and gene
      expression in neuropathic pain models].

PMID- 9921191
TI  - [Neuropathic pain--variability in pain maintaining mechanism].

PMID- 9921192
TI  - Pharmacological and neuroanatomical studies of the antinociceptive effects of
      intrathecally administered gabapentin.

PMID- 9921193
TI  - [Various factors contributing to the development of liver transplantation].

PMID- 9921194
TI  - [Liver protection and liver transplantation from a living donor for the treatment
      of acute hepatic failure].

PMID- 9921195
TI  - [Liver transplantation--a viewpoint of anesthesiologists in charge of the
      perioperative period].

PMID- 9921196
TI  - [Suggestions and expectations on anesthesiologists involved in organ
      transplantation].

PMID- 9921197
TI  - [Keypoints in response to infections in Japan].

PMID- 9921198
TI  - [Bacterial sensitivity test to formulate an anti-infective strategy].

PMID- 9921199
TI  - [Rapid diagnosis of enterohemorrhagic Escherichia coli infection].

PMID- 9921200
TI  - [Diagnosis of infections with difficulty in isolation and identification of the
      causative agent. 1) Legionellosis].

PMID- 9921201
TI  - [Diagnosis of infections with difficulty in isolation and identification of
      causative organisms. 2) Chlamydia pneumoniae infection].

PMID- 9921202
TI  - [Diagnosis of infections with difficulty in isolation and identification of the
      causative organisms. 3) Acid-fast bacterial infections (caused by Mycobacterium
      tuberculosis or atypical acid-fast organisms)].

PMID- 9921203
TI  - [Diagnosis of infections with difficulty in isolation and identification of
      causative organisms. 4) Deep mycosis].

PMID- 9921204
TI  - [Diagnosis of infections with difficulty in isolation and identification of
      causative agents. 5) Virus infections].

PMID- 9921205
TI  - [Collection of samples, their management and examination to identify the
      causative organisms].

PMID- 9921206
TI  - [Advances in anti-infective agents and methods for their application].

PMID- 9921207
TI  - [Systemic management of patients under anti-infection treatment].

PMID- 9921208
TI  - [Advances in the treatment of severe refractory infections. 1) HIV infections].

PMID- 9921209
TI  - [Advances in the treatment of severe refractory diseases. 2) Viral hepatitis].

PMID- 9921210
TI  - [Advances in the treatment of severe refractory diseases. 3) Septicemia].

PMID- 9921211
TI  - [Advances in the treatment of severe refractory infections. 4) Deep fungal
      infection].

PMID- 9921212
TI  - [Treatment of infections of the current interest. 1) Helicobacter pylori
      infection].

PMID- 9921213
TI  - [Treatment of infections of current interest. 2) Biofilm infection].

PMID- 9921214
TI  - [Treatment of infections of the current interest. 3) Malignant malaria].

PMID- 9921215
TI  - [Advances in diagnosis and treatment of infections: discussion].

PMID- 9921216
TI  - [Probable case of Chinese herbs nephropathy].

PMID- 9921217
TI  - [Case of septicemia caused by Klebsiella pneumonia and systemic multiple
      abscess].

PMID- 9921218
TI  - [Case of hypothyroidism and hypoparathyroidism discovered by fainting spells].

PMID- 9921219
TI  - [Rare case of ulcerative colitis and ankylosing spondylitis associated with
      aortitis and severe aortic valve insufficiency].

PMID- 9921220
TI  - [Case of retroperitoneal fibrosis exhibiting a variety of auto- antibodies and
      complicated by Sjogren's syndrome].

PMID- 9921222
TI  - [Early colonic cancer with a surface depression].

PMID- 9921221
TI  - [Genetic diagnosis of hereditary diseases].

PMID- 9921223
TI  - [Molecular biological mechanism for the development of cystic kidney].

PMID- 9921225
TI  - [Viral morphology, structure, and classification].

PMID- 9921224
TI  - [Kidney disorder caused by contrast media].

PMID- 9921226
TI  - [Virus infections, their onsets, and immunology].

PMID- 9921227
TI  - [Viral isolation and identification].

PMID- 9921228
TI  - [Detection of viral antigens and viral genes].

PMID- 9921229
TI  - [Serodiagnosis of viral infections].

PMID- 9921230
TI  - [Chemotherapy and vaccines used for the management of viral infections].

PMID- 9921231
TI  - [Laboratory diagnosis of viral infections. 1. Respiratory tract infections].

PMID- 9921232
TI  - [Laboratory diagnosis of viral infections. 2. Nervous system infections].

PMID- 9921233
TI  - [Laboratory diagnosis of viral infections. 3. Exanthema and muco- cutaneous
      infections].

PMID- 9921235
TI  - [Laboratory diagnosis of viral infections. 5. Viral hepatitis].

PMID- 9921234
TI  - [Laboratory diagnosis of viral infections. 4. Viral food poisoning,
      gastroenteritis, and diarrhea].

PMID- 9921236
TI  - [Laboratory diagnosis of viral infections. 6. Tumor viruses].

PMID- 9921237
TI  - [Laboratory diagnosis of viral infections. 7. Opportunistic infection by
      herpesviruses (human cytomegalovirus, Epstein-Barr virus, and human herpesvirus
      8)].

PMID- 9921238
TI  - [Laboratory diagnosis of viral infections. 8. Viral hemorrhagic fever].

PMID- 9921239
TI  - [Laboratory diagnosis of viral infections. 9. Viral infections related to blood
      transfusion and organ transplantation].

PMID- 9921240
TI  - [Laboratory diagnosis of viral infections. 10. Circulatory and muscular diseases
      and arthritis caused by virus infections].

PMID- 9921241
TI  - [Laboratory diagnosis of viral infections. 11. Ocular diseases].

PMID- 9921242
TI  - [Laboratory diagnosis of viral infections. 12. Urogenital diseases and sexually
      transmitted diseases].

PMID- 9921243
TI  - [Recent trend in parasitic diseases in Japan (with a list of diagnosis and
      treatment of parasitic diseases)].

PMID- 9921244
TI  - [Current status of imported parasitic diseases in Japan].

PMID- 9921245
TI  - [Zoonotic parasitic diseases recently observed in Japan].

PMID- 9921246
TI  - [Diagnosis of parasitic diseases].

PMID- 9921247
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. Protozoan
      infections. a. Malaria].

PMID- 9921248
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. Protozoan
      infections. b. Amebic dysentery].

PMID- 9921249
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. protozoan
      infections. c. Acanthamoeba infection].

PMID- 9921250
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. Protozoan
      infections. d. Cryptosporidium infections].

PMID- 9921252
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. Protozoan
      infections. f. Toxoplasmosis].

PMID- 9921251
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 1. Protozoan
      infections. e. Isospora and Cyclospora infections].

PMID- 9921253
TI  - [Laboratory diagnosis of protozoan and parasitic diseases. 2. Helminthiasis. a.
      Sparganosis].

PMID- 9921254
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. b.
      Diphyllobothrium infections].

PMID- 9921255
TI  - [Laboratory diagnosis of protozoan and parasitic diseases. 2. Helminthiasis. c.
      Echinococcosis].

PMID- 9921256
TI  - [Laboratory diagnosis of protozoan and parasitic diseases. 2. Helminthiasis. d.
      Trematode infections].

PMID- 9921257
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. e.
      Anisakiasis].

PMID- 9921258
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. f.
      Angiostrongyliasis cantonensis].

PMID- 9921259
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. g.
      Dirofilariasis (with special reference to Dirofilaria immitis infection)].

PMID- 9921260
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. h.
      Toxocariasis].

PMID- 9921261
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. i.
      Spirurida infections].

PMID- 9921262
TI  - [Laboratory diagnosis of protozoan and parasitic infections. 2. Helminthiasis. j.
      Strongyloides stercoralis infection].

PMID- 9921263
TI  - [Development of aromatase inhibitors and analysis of their inhibitory
      activities].
AB  - Inhibitors of aromatase are of interest in the treatment of advanced estrogen
      dependent breast cancers. In addition, the inhibitors are promising to play as
      conformational and catalytic probes for the active site of this enzyme,
      aromatase. There fore, we synthesized a number of steroidal aromatase inhibitors,
      including suicide substrates, and also studied the mechanism for a time-dependent
      inactivation of aromatase by the suicide substrates. The mechanism for the
      aromatase inactivation by 6-oxo-androstenedione (AD) (1), one of the first
      discovered suicide substrates, was explored using the 19-substituted analogs 2-5
      as well as stereo- and/or regio-specifically labeled [3H, 14C]-compound 1. The
      results indicated that the 4 beta,5 beta-epoxy-19-oxo derivative 7 is a reactive
      electrophile that irreversibly binds to the active site of aromatase. Studies on
      the aromatase inhibition by regioisomers of AD, 4-en-6-one 17, 5-en-4-one 18 and
      5-en-7-one 19, revealed that the C-3 carbonyl function is not essential for the
      tight binding of an inhibitor to the active site. 3-Deoxy AD (22) and its 6
      alpha,7 alpha-cyclopropano steroid 24 as well as some of 6-alkyl-ADs are among
      the most potent competitive inhibitors reported so for (K(m) for AD/Ki > 6).
      Structure-activity relationships of the 6-alkyl-ADs and their 3-deoxy-, delta 1-,
      delta 6-, and delta 1,6-analogs as aromatase inhibitors showed that aromatase has
      a hydrophobic binding pocket with a limited accessible volume in the active site
      in the region corresponding to the beta-side rather than the alpha-side of the C
      6 position of the substrate. The 6-alkyl-ADs and their delta 1-analogs were
      converted into the corresponding estrogens with human placental aromatase,
      whereas the 3-deoxy steroids 22 and 25 were metabolized to the corresponding 19
      oxygenated compounds. The relative apparent K(m) values for the androgens are
      different from the relative Ki values, indicating that there is a difference
      between the ability to serve as an inhibitor and that to serve as a substrate.
      Moreover, it seems likely that the alignment of the substrate AD analogs in the
      active site would be markedly different from that of the 3-deoxy steroids.

PMID- 9921264
TI  - [Development of high-performance frontal analysis and application to drug-plasma
      protein binding study].
AB  - This review summarizes the principle and the features of high-performance frontal
      analysis (HPFA), a novel chromatographic method to determine the concentrations
      of unbound drugs under drug-protein binding equilibrium conditions, and its
      application to the study on the plasma protein binding. HPFA uses a "restricted
      access" type HPLC column which retains a small molecule in the drugs in the
      micropores, while a large molecule in the plasma protein is size-excluded. After
      direct and continuous injection of a sample, the drug-protein binding equilibrium
      in the sample solution is regenerated in the column, and the constant
      concentration zone of the unbound drug appears from the equilibrium zone. The
      unbound drug is eluted as a trapezoidal peak with a plateau. The concentration in
      this plateau region is equal to that of the unbound drug in the sample solution,
      and the concentration of the unbound drug can be determined by subsequent on-line
      HPLC analysis. HPFA allows a simple analysis following direct injection of a
      sample, and does not cause undesirable drug adsorption on the membrane nor
      leakage of the bound drug from the membrane, which are often encountered in the
      conventional ultrafiltration or dialysis method. HPFA allows the simultaneous
      determination of the concentrations of total and unbound drugs in a single
      analysis. HPFA can be easily incorporated into the on-line HPLC system. By
      coupling HPFA with a chiral HPLC column, the concentration of an unbound racemic
      drug can be determined enantioselectively. The detection limit can be improved
      dramatically by coupling HPEA with a preconcentration column. Frontal analysis in
      capillary electrophoresis format (CE/FA) allows us an ultramicro binding assay.
      The concentration of the unbound racemic drug can be determined stereoselectively
      by coupling HPFA with a chiral CE technique.

PMID- 9921265
TI  - [Identification of biologically active sites in laminin an extracellular matrix
      protein].
AB  - Laminin-1, a major component of basement membranes, has multiple biological
      activities including promotion of cell adhesion, spreading, migration, growth,
      neurite outgrowth and tumor metastasis. Several active sites on laminin-1 have
      been identified previously. We modified these biologically active peptides to
      enhance their activities. The multimeric YIGSR (Tyr-Ile-Gly-Ser-Arg) peptides
      assembled on a branched lysine core were found to strongly enhance the activity
      of YIGSR in inhibiting tumor growth and metastasis. We also found the all-D
      configuration peptide segment containing the IKVAV (Ile-Lys-Val-Ala-Val) sequence
      had similar biological activities to the native all-L-peptide in vitro and in
      vivo. These results suggest that these modified compounds are potentially useful
      for clinical applications. We have identified new active sequences from the
      laminin alpha 1 chain carboxyl-terminal globular domain (G domain). Using a
      systematic screening for cell binding sites with 113 overlapping synthetic
      peptides, we found five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed
      cell attachment activities with cell-type specificities. AG-10 and AG-32 were
      found to interact with integrins. AG-73 caused metastases of B16-F10 mouse
      melanoma cells to the liver colonization in mice. Additionally AG-73 was found to
      promote neurite outgrowth. Moreover, this peptide inhibited laminin mediated
      acinar-like development of a human submandibular gland cell line. The AG-73
      domain on laminin-1 could be one of the most important biologically active sites.
      These active peptides may useful for study of the molecular mechanism of laminin
      receptor interactions and for development of therapeutic reagents for tumor
      metastasis and angiogenasis.

PMID- 9921266
TI  - [The cause of polyurethane catheter cracking during constant infusion of
      etoposide (VP-16) injection].
AB  - We studied the cause of cracking of a clinically used polyurethane (PU) catheter
      during the constant infusion of etoposide (VP-16) injection (Lastet),
      administered without dilution to patients as a part of combination high-dose
      chemotherapy. After VP-16 injection was infused into the PU catheter at a
      constant infusion rate (30 ml/h) for 24 h, a decrease in the elasticity (36% of
      untreated) and on increase in the length of the catheter (3.7%) were observed.
      These changes were significantly higher than those treated with the control
      saline. The similar changes of the PU catheter were observed after treatment with
      a basal solution containing polyethylene glycol 400 (PEG 400), polysorbate 80 and
      ethanol, which is the vehicle of the VP-16 injection, and with ethanol alone.
      Moreover, obvious degeneration of the internal wall (occurrence of spots like
      melting) and cutting face (micro-cracking) of the catheter was observed with an
      electron microscope after treatment with the vehicle. On the other hand, the
      elasticity or extension of the PU catheter were not changed after treatment with
      saline or PEG 400. From these findings, it was suggested that the degeneration
      and subsequent cracking of the PU catheter during the infusion of VP-16 injection
      was caused by ethanol contained in its injection solution. No cracking or
      morphological changes of polyvinyl chloride (PVC) and silicone catheters were
      found after treatment with the vehicle solution. However, since it has been
      reported in previous reports that di(2-ethylhexyl)phthalate was leached from PVC
      bags, the high dose chemotherapy with the dilution-free VP-16 injection should be
      achieved safely and effectively using a silicon catheter, rather than the PU
      catheter.

PMID- 9921267
TI  - [Effect of shikonin and alkannin on hydroxyl radical generation system concerned
      with iron ion].
AB  - The effects of shikonnin (SK) and its optical isomer alkannin (AK) on the
      hydroxyl radical (HO.) generation system including iron ions were evaluated using
      the spin trap method by ESR spectroscopy. 5,5-Dimethyl-1-pyrroline-1-oxide (DMPO)
      was used as a spin trap agent and HO. was generated by a reaction between an iron
      ion and hydrogen peroxide, which is called Fenton reaction system. SK inhibited
      the HO. spin adduct (DMPO-OH) yielded in a dose-dependent manner. In this effect
      no difference was observed between SK and AK. When different concentrations of
      DMPO were used for the confirmation of its competitive reaction, no difference
      was also observed in the concentration of SK required to reduce the amount of the
      DMPO-OH by 50% (ID50). These findings suggested that the inhibitory effect of SK
      against the thus yielded DMPO-OH was not generated by the scavenging for HO., but
      by the inhibition on the Fenton reaction system. The mechanism of the inhibition
      on this system may be based on the formation of a complex between SK and the iron
      ion. The molar ratio of SK to the iron ion in the complex was considered 2 to 1
      (2:1), because the concentrations of the observed ID50 and the used iron ion
      exhibited the same value. In addition, the same result was also obtained from the
      study using spectroscopic analysis.

PMID- 9921268
TI  - [Inhibition of mycelial growth of Candida albicans by ascites fluid of tumor
      bearing mice].
AB  - The effects of ascites fluids and sera of tumor-bearing mice on the mycelial
      growth of Candida albicans were examined. When the ascites fluids or the sera
      obtained from mice inoculated with MM46 mammary carcinoma were added to the
      culture medium, mycelial growth of C. albicans was strongly inhibited. The
      molecular size of the growth inhibitory factor in the ascites fluids was
      estimated to be approximately 80 K dalton by gel-filtration chromatography.
      Ferric chloride (6 microM) neutralized the anti-Candida activity. On the basis of
      these results including morphological observation, a possible role of a
      transferrin-like molecule was discussed.

PMID- 9921269
TI  - Brazilian biodiversity.
AB  - Comments are made about Brazil's rich biological patrimony, the value of which is
      still impossible to be appraised in a judicious manner. We are dealing with a
      highly valuable unknown and, for this very reason, still not utilised in a
      rational manner. The most extremely serious aspect, however, is the destruction
      that has for centuries affected the natural ecosystems and their respective wild
      biotas, even before their being scientifically better know. The importance of
      utilising this natural patrimony is emphasised, as well as the native domestic
      races of plants and animals that have been molded for centuries by Brazilian
      environmental conditions, and that nowadays represent valuable genetic material
      for agronomic and zootechnical research. The conference ends with remarks about
      the imbalance and environmental disasters, as well as the destruction of
      biodiversity, that have occurred in the Northeast of Brazil due mainly to the
      massive and irresponsible forestal devastation in the region.

PMID- 9921270
TI  - Purification and binding analysis of the nitrogen fixation regulatory NifA
      protein from Azospirillum brasilense.
AB  - NifA protein activates transcription of nitrogen fixation operons by the
      alternative sigma 54 holoenzyme form of RNA polymerase. This protein binds to a
      well-defined upstream activator sequence (UAS) located at the -200/-100 position
      of nif promoters with the consensus motif TGT-N10-ACA. NifA of Azospirillum
      brasilense was purified in the form of a glutathione-S-transferase (GST)-NifA
      fusion protein and proteolytic release of GST yielded inactive and partially
      soluble NifA. However, the purified NifA was able to induce the production of
      specific anti-A. brasilense NifA-antiserum that recognized NifA from A.
      brasilense but not from K. pneumoniae. Both GST-NifA and NifA expressed from the
      E. coli tac promoter are able to activate transcription from the nifHDK promoter
      but only in an A. brasilense background. In order to investigate the mechanism
      that regulates NifA binding capacity we have used E. coli total protein extracts
      expressing A. brasilense nifA in mobility shift assays. DNA fragments carrying
      the two overlapping, wild-type or mutated UAS motifs present in the nifH promoter
      region revealed a retarded band of related size. These data show that the binding
      activity present in the C-terminal domain of A. brasilense NifA protein is still
      functional even in the presence of oxygen.

PMID- 9921271
TI  - A chromatographic method for the production of a human immunoglobulin G solution
      for intravenous use.
AB  - Immunoglobulin G (IgG) of excellent quality for intravenous use was obtained from
      the cryosupernatant of human plasma by a chromatographic method based on a
      mixture of ion-exchange, DEAE-Sepharose FF and arginine Sepharose 4B affinity
      chromatography and a final purification step by Sephacryl S-300 HR gel
      filtration. The yield of 10 experimental batches produced was 3.5 g IgG per liter
      of plasma. A solvent/detergent combination of 1% Tri (n-butyl) phosphate and 1%
      Triton X-100 was used to inactivate lipid-coated viruses. Analysis of the final
      product (5% liquid IgG) based on the mean for 10 batches showed 94% monomers,
      5.5% dimers and 0.5% polymers and aggregates. Anticomplementary activity was 0.3
      CH50/mg IgG and prekallikrein activator levels were less than 5 IU/ml. Stability
      at 37 degrees C for 30 days in the liquid state was satisfactory. IgG was stored
      in flasks (2.5 g/flask) at 4 to 8 degrees C. All the characteristics of the
      product were consistent with the requirements of the 1997 Pharmacopee Europeenne.

PMID- 9921272
TI  - Purification of human albumin by the combination of the method of Cohn with
      liquid chromatography.
AB  - Large volumes of plasma can be fractionated by the method of Cohn at low cost.
      However, liquid chromatography is superior in terms of the quality of the product
      obtained. In order to combine the advantages of each method, we developed an
      integrated method for the production of human albumin and immunoglobulin G (IgG).
      The cryoprecipitate was first removed from plasma for the production of factor
      VIII and the supernatant of the cryoprecipitate was fractionated by the method of
      Cohn. The first precipitate, containing fractions (F)-I + II + III, was used for
      the production of IgG by the chromatographic method (see Tanaka K et al. (1998)
      Brazilian Journal of Medical and Biological Research, 31: 1375-1381). The
      supernatant of F-I + II + III was submitted to a second precipitation and F-IV
      was obtained and discarded. Albumin was obtained from the supernatant of the
      precipitate F-IV by liquid chromatography, ion-exchange on DEAE-Sepharose FF,
      filtration through Sephacryl S-200 HR and introduction of heat treatment for
      fatty acid precipitation. Viral inactivation was performed by pasteurization at
      60 degrees C for 10 h. The albumin product obtained by the proposed procedure was
      more than 99% pure for the 15 lots of albumin produced, with a mean yield of 25.0
      +/- 0.5 g/l plasma, containing 99.0 to 99.3% monomer, 0.7 to 1.0% dimers, and no
      polymers. Prekallikrein activator levels were < or = 5 IU/ml. This product
      satisfies the requirements of the 1997 Pharmacopee Europeenne.

PMID- 9921273
TI  - JAK/STAT-deficient cell lines.
AB  - Mutant cell lines B3 and B10, which are unresponsive to both interferon (IFN)
      alpha and IFN-gamma, and line B9, which does not respond to IFN-gamma
      stimulation, are described. The mutants were submitted to fluorescence-activated
      cell sorting (FACS) from a cellular pool, which was obtained from the parental
      cell line 2C4 after several rounds of mutagenesis. The unresponsiveness to IFN
      stimulation was observed both in terms of expression of cell surface markers
      (CD2, class I and II HLAs) and mRNA expression of IFN-stimulated genes (2'-5'
      oligoadenylate synthetase (OAS), 9-27, and guanylate binding protein (GBP)).
      Genetic crossing of B3, B9 and B10 with U3 (STAT1-), gamma 2a (JAK2-) and U4
      (JAK1-) mutants, respectively, did not restore IFN responsiveness to the hybrid
      cell lines. However, when these cell lines were crossed with the same mutants,
      but using the pairwise crosses B3 x U4, B9 x U3 and B10 x U3, the cell hybrids
      recovered full IFN responsiveness. The present genetic experiments permitted us
      to assign the mutant cell lines B3, B9 and B10 to the U3, gamma 2 and U4
      complementation groups, respectively. These conclusions were supported by the
      analysis of IFN-stimulated genes in the mutants.

PMID- 9921274
TI  - Human group C rotavirus in children with diarrhea in the Federal District,
      Brazil.
AB  - Group C rotaviruses are fastidious in their in vitro cell culture requirements.
      Recent serosurveys indicate that antibody to group C rotavirus is present in 3
      45% of the human population in certain geographic locations, suggesting that
      rotavirus group C infection is more prevalent than previously believed and that
      the low rate of detection of these agents is probably due to the lack of
      sensitive diagnostic assays. From March to December 1994, 406 fecal specimens
      were collected from children under five years of age who were outpatients at the
      emergency services of nine public hospitals in Brasilia, Federal District,
      Brazil. In addition to the samples from children, one public outpatient unit
      requested virological investigation of a stool sample from an HIV-seropositive
      adult male with diarrhea of sudden onset. All samples were analyzed by enzyme
      immunoassay for group A rotavirus and adenovirus (EIARA) and by polyacrylamide
      gel electrophoresis (PAGE). One hundred and seven (26%) were positive for group A
      rotavirus. Four samples from children and the sample from the HIV-seropositive
      patient, although negative by EIARA, showed a group C rotavirus profile by PAGE
      and were positive for rotavirus by electron microscopy. Using specific VP6 and
      VP7 primers for group C rotavirus, a reverse transcriptase-polymerase chain
      reaction (RT-PCR) was performed and products were detected by agarose gel
      electrophoresis and ethidium bromide staining. These products were confirmed to
      be specific for group C rotavirus by using digoxigenin-oligonucleotide probes,
      Southern hybridization and chemiluminescent detection. The five positive group C
      rotavirus samples were detected in August (3 samples) and September (2 samples).
      To the best of our knowledge, this is the first report of group C rotavirus
      detected in the Federal District, Brazil and in an HIV-seropositive patient with
      acute gastroenteritis.

PMID- 9921275
TI  - Association of hepatic nuclear factor-4 in the apolipoprotein B promoter: a
      preliminary report.
AB  - Previous studies have examined the arrangement of regulatory elements along the
      apolipoprotein B (apoB) promoter region (-3067 to +940) and a promoter fragment
      extending from nucleotides -150 to +124 has been demonstrated to be essential for
      transcriptional activation of the apoB gene in hepatic and intestinal cells. It
      has also been shown that transcriptional activation of apoB requires a
      synergistic interaction between hepatic nuclear factor-4 (HNF-4) and
      CCAAT/enhancer-binding protein alpha (C/EBP alpha) transcription factors. Here,
      we have examined the hypothesis that HNF-4 factor binding to DNA may induce a DNA
      helix bend, thus facilitating the communication with a C/EBP alpha factor located
      one helix turn from this HNF-4 factor in the apoB promoter. A gel electrophoretic
      mobility shift assay using wild type double-stranded oligonucleotides or modified
      wild type duplex oligonucleotides with 10 nucleotides inserted between HNF-4 and
      C/EBP alpha factor motifs showed similar retarded complexes, indicating that HNF
      4 and C/EBP alpha factors interact independently of the distance between binding
      sites. However, when only one base, a thymidine, was inserted at the -71 position
      of the apoB promoter, the complex shift was completely abolished. In conclusion,
      these results regarding the study of the mechanisms involving the interaction
      between HNF-4 and C/EBP alpha factors in the apoB promoter suggest that the
      perfect 5'-CCCTTTGGA-3' motif is needed in order to facilitate the interaction
      between the two factors.

PMID- 9921276
TI  - The insulin receptor substrate 1 associates with phosphotyrosine phosphatase
      SHPTP2 in liver and muscle of rats.
AB  - Insulin stimulates the tyrosine kinase activity of its receptor resulting in the
      phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1)
      which, in turn, associates with proteins containing SH2 domains. It has been
      shown that IRS-1 associates with the tyrosine phosphatase SHPTP2 in cell
      cultures. While the effect of the IRS-1/SHPTP2 association on insulin signal
      transduction is not completely known, this association may dephosphorylate IRS-1
      and may play a critical role in the mitogenic actions of insulin. However, there
      is no physiological demonstration of this pathway of insulin action in animal
      tissues. In the present study we investigated the ability of insulin to induce
      association between IRS-1 and SHPTP2 in liver and muscle of intact rats, by co
      immunoprecipitation with anti-IRS-1 antibody and anti-SHPTP2 antibody. In both
      tissues there was an increase in IRS-1 association with SHPTP2 after insulin
      stimulation. This association occurred when IRS-1 had the highest level of
      tyrosine phosphorylation and the decrease in this association was more rapid than
      the decrease in IRS-1 phosphorylation levels. The data provide evidence against
      the participation of SHPTP2 in IRS-1 dephosphorylation in rat tissues, and
      suggest that the insulin signal transduction pathway in rat tissues is related
      mainly to the mitogenic effects of the hormone.

PMID- 9921277
TI  - Insulin receptor has tyrosine kinase activity toward Shc in rat liver.
AB  - Insulin induces tyrosine phosphorylation of Shc in cell cultures and in insulin
      sensitive tissues of the intact rat. However, the ability of insulin receptor
      (IR) tyrosine kinase to phosphorylate Shc has not been previously demonstrated.
      In the present study, we investigated insulin-induced IR tyrosine kinase activity
      towards Shc. Insulin receptor was immunoprecipitated from liver extracts, before
      and after a very low dose of insulin into the portal vein, and incubated with
      immunopurified Shc from liver of untreated rats. The kinase assay was performed
      in vitro in the presence of exogenous ATP and the phosphorylation level was
      quantified by immunoblotting with antiphosphotyrosine antibody. The results
      demonstrate that Shc interacted with insulin receptor after infusion of insulin,
      and, more important, there was insulin receptor kinase activity towards
      immunopurified Shc. The description of this pathway in animal tissue may have an
      important role in insulin receptor tyrosine kinase activity toward mitogenic
      transduction pathways.

PMID- 9921278
TI  - Coupling of palmitate to ovalbumin inhibits the induction of oral tolerance.
AB  - Oral tolerance is a phenomenon that may occur in animals exposed to protein
      antigens for the first time by the oral route. They become unable to produce
      immune responses at the levels normally observed when they are immunized
      parenterally with antigen in the presence of adjuvants. Lipids have been used as
      adjuvants for both parenteral and oral immunization. In the present study we
      coupled ovalbumin with palmitate residues by incubating the protein with the N
      hydroxysuccinimide palmitate ester and tested the preparation for its ability to
      induce oral tolerance. This was performed by giving 20 mg of antigen to mice by
      the oral route 7 days prior to parenteral immunization in the presence of
      A1(OH)3. Mice were bled one week after receiving a booster that was given 2 weeks
      after primary immunization. Specific antibodies were detected by ELISA. Despite
      the fact that the conjugates are as immunogenic as the unmodified protein when
      parenterally injected in mice, they failed to induce oral tolerance. This
      discrepancy could be explained by differences in the intestinal absorption of the
      two forms of the antigen. In fact, when compared to the non-conjugated ovalbumin,
      a fast and high absorption of the lipid-conjugated form of ovalbumin was observed
      by "sandwich" ELISA.

PMID- 9921279
TI  - Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini
      infected YAC-1 tumor cells.
AB  - Macrophages are important components of natural immunity involved in inhibition
      of tumor growth and destruction of tumor cells. It is known that these cells can
      be activated for tumoricidal activity by lymphokines and bacterial products. We
      investigated whether YAC-1 tumor cells infected with Mycoplasma arginini
      stimulate nitric oxide (NO) release and macrophage cytotoxic activity.
      Thioglycollate-elicited macrophages from male BALB/c mice were co-cultured for 20
      h with YAC-1 tumor cells infected or not with Mycoplasma arginini. The cytotoxic
      activity was evaluated by MTT assay and nitrite levels were determined with the
      Griess reagent. Thioglycollate-elicited macrophages co-cultured with noninfected
      YAC-1 cells showed low cytotoxic activity (34.7 +/- 8.6%) and low production of
      NO (4.7 +/- 3.1 microM NO2-). These macrophages co-cultured with mycoplasma
      infected YAC-1 cells showed significantly higher cytotoxic activity (61.4 +/-
      9.1%; P < 0.05) and higher NO production (48.5 +/- 13 microM NO2-; P < 0.05).
      Addition of L-NAME (10 mM), an inhibitor of NO synthesis, to these co-cultures
      reduced the cytotoxic activity to 37.4 +/- 2% (P < 0.05) and NO production to 3
      +/- 4 microM NO2- (P < 0.05). The present data show that Mycoplasma arginini is
      able to induce macrophage cytotoxic activity and that this activity is partially
      mediated by NO.

PMID- 9921280
TI  - Antigenic characterization of Brazilian bovine viral diarrhea virus isolates by
      monoclonal antibodies and cross-neutralization.
AB  - Nineteen Brazilian isolates of bovine viral diarrhea virus (BVDV) were
      characterized antigenically with a panel of 19 monoclonal antibodies (mAbs)
      (Corapi WV, Donis RO and Dubovi EJ (1990) American Journal of Veterinary
      Research, 55: 1388-1394). Eight isolates were further characterized by cross
      neutralization using sheep monospecific antisera. Analysis of mAb binding to
      viral antigens by indirect immunofluorescence revealed distinct patterns of
      reactivity among the native viruses. Local isolates differed from the prototype
      Singer strain in recognition by up to 14 mAbs. Only two mAbs--one to the non
      structural protein NS23/p125 and another to the envelope glycoprotein E0/gp48-
      recognized 100% of the isolates. No isolate was recognized by more than 14 mAbs
      and twelve viruses reacted with 10 or less mAbs. mAbs to the major envelope
      glycoprotein E2/gp53 revealed a particularly high degree of antigenic variability
      in this glycoprotein. Nine isolates (47.3%) reacted with three or less of 10
      E2/gp53 mAbs, and one isolate was not recognized by any of these mAbs. Virus
      specific antisera to eight isolates plus three standard BVDV strains raised in
      lambs had virus-neutralizing titers ranging from 400 to 3200 against the
      homologous virus. Nonetheless, many antisera showed significantly reduced
      neutralizing activity when tested against heterologous viruses. Up to 128-fold
      differences in cross-neutralization titers were observed for some pairs of
      viruses. When the coefficient of antigenic similarity (R) was calculated, 49 of
      66 comparisons (74.24%) between viruses resulted in R values that antigenically
      distinguish strains. Moreover, one isolate had R value suggesting that it belongs
      to a distinct serologic group. The marked antigenic diversity observed among
      Brazilian BVDV isolates should be considered when planning diagnostic and
      immunization strategies.

PMID- 9921281
TI  - Effects of sciatic-conditioned medium on neonatal rat retinal cells in vitro.
AB  - Schwann cells produce and release trophic factors that induce the regeneration
      and survival of neurons following lesions in the peripheral nerves. In the
      present study we examined the in vitro ability of developing rat retinal cells to
      respond to factors released from fragments of sciatic nerve. Treatment of
      neonatal rat retinal cells with sciatic-conditioned medium (SCM) for 48 h induced
      an increase of 92.5 +/- 8.8% (N = 7 for each group) in the amount of total
      protein. SCM increased cell adhesion, neuronal survival and glial cell
      proliferation as evaluated by morphological criteria. This effect was completely
      blocked by 2.5 microM chelerythrine chloride, an inhibitor of protein kinase C
      (PKC). These data indicate that PKC activation is involved in the effect of SCM
      on retinal cells and demonstrate that fragments of sciatic nerve release trophic
      factors having a remarkable effect on neonatal rat retinal cells in culture.

PMID- 9921282
TI  - Decreased spermatogenic and androgenic testicular functions in adult rats
      submitted to immobilization-induced stress from prepuberty.
AB  - We investigated whether chronic stress applied from prepuberty to full sexual
      maturity interferes with spermatogenic and androgenic testicular functions. Male
      Wistar rats (40 days old) were immobilized 6 h a day for 60 days. Following
      immobilization, plasma concentrations of corticosterone and prolactin increased
      135% and 48%, respectively, while plasma luteinizing hormone and testosterone
      presented a significant decrease of 29% and 37%, respectively. Plasma
      concentration of follicle-stimulating hormone was not altered in stressed rats.
      Chronic stress reduced the amount of mature spermatids in the testis by 16% and
      the spermatozoon concentration in the cauda epididymidis by 32%. A 17% reduction
      in weight and a 42% decrease in DNA content were observed in the seminal vesicle
      of immobilized rats but not in its fructose content. The growth and secretory
      activity of the ventral prostate were not altered by chronic stress.

PMID- 9921283
TI  - Karyological, biochemical, and physiological aspects of Callophysus macropterus
      (Siluriformes, Pimelodidae) from the Solimoes and Negro Rivers (central Amazon).
AB  - Karyological characteristics, i.e., diploid number, chromosome morphology and
      nucleolus organizer regions (NORs), biochemical characteristics, i.e.,
      electrophoretic analysis of blood hemoglobin and the tissue enzymes lactate
      dehydrogenase (LDH), malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), and
      phosphoglucose isomerase (PGI), and physiological characteristics, i.e., relative
      concentration of hemoglobin and intraerythrocytic concentrations of organic
      phosphates were analyzed for the species Callophysus macropterus collected from
      Marchantaria Island (white water system--Solimoes River) and Anavilhanas
      Archipelago (black water system--Negro River). Karyological and biochemical data
      did not reveal significant differences between specimens collected at the two
      sites. However, the relative distribution of hemoglobin bands I and III (I =
      16.33 +/- 1.05 and III = 37.20 +/- 1.32 for Marchantaria specimens and I = 6.33
      +/- 1.32 and III = 48.05 +/- 1.55 for Anavilhanas specimens) and levels of
      intraerythrocytic GTP (1.32 +/- 0.16 and 2.76 +/- 0.18 for Marchantaria and
      Anavilhanas specimens, respectively), but not ATP or total phosphate, were
      significantly different, indicating a physiological adaptation to the
      environmental conditions of these habitats. It is suggested that C. macropterus
      specimens from the two collecting sites belong to a single population, and that
      they adjusted some physiological characteristics to adapt to local environmental
      conditions.

PMID- 9921284
TI  - The use of confocal laser scanning microscopy to analyze the process of parasitic
      protozoon-host cell interaction.
AB  - In this communication we review the results obtained with the confocal laser
      scanning microscope to characterize the interaction of epimastigote and
      trypomastigote forms of Trypanosoma cruzi and tachyzoites of Toxoplasma gondii
      with host cells. Early events of the interaction process were studied by the
      simultaneous localization of sites of protein phosphorylation, revealed by
      immunocytochemistry, and sites of actin assembly, revealed by the use of labeled
      phaloidin. The results obtained show that proteins localized in the interaction
      sites are phosphorylated. The process of formation of the parasitophorous vacuole
      was monitored by labeling the host cell surface with fluorescent probes for
      lipids (PKH26), proteins (DTAF) and sialic acid (FITC-thiosemicarbazide) before
      interaction with the parasites. Evidence was obtained indicating transfer of
      components of the host cell surface to the parasite surface in the beginning of
      the interaction process. We also analyzed the distribution of cytoskeletal
      structures (microtubules and microfilaments visualized with specific antibodies),
      mitochondria (visualized with rhodamine 123), the Golgi complex (visualized with
      C6-NBD-ceramide) and the endoplasmic reticulum (visualized with anti-reticulin
      antibodies and DIOC6) during the evolution of intracellular parasitism. The
      results obtained show that some, but not all, structures change their position
      during evolution of the intracellular parasitism.

PMID- 9921285
TI  - Using green fluorescent protein to understand the mechanisms of G-protein-coupled
      receptor regulation.
AB  - G protein-coupled receptor (GPCR) activation is followed rapidly by adaptive
      changes that serve to diminish the responsiveness of a cell to further
      stimulation. This process, termed desensitization, is the consequence of receptor
      phosphorylation, arrestin binding, sequestration and down-regulation. GPCR
      phosphorylation is initiated within seconds to minutes of receptor activation and
      is mediated by both second messenger-dependent protein kinases and receptor
      specific G protein-coupled receptor kinases (GRKs). Desensitization in response
      to GRK-mediated phosphorylation involves the binding of arrestin proteins that
      serve to sterically uncouple the receptor from its G protein. GPCR sequestration,
      the endocytosis of receptors to endosomes, not only contributes to the temporal
      desensitization of GPCRs, but plays a critical role in GPCR resensitization. GPCR
      down-regulation, a loss of the total cellular complement of receptors, is the
      consequence of both increased lysosomal degradation and decreased mRNA synthesis
      of GPCRs. While each of these agonist-mediated desensitization processes are
      initiated within a temporally dissociable time frame, recent data suggest that
      they are intimately related to one another. The use of green fluorescent protein
      from the jellyfish Aqueora victoria as an epitope tag with intrinsic fluorescence
      has facilitated our understanding of the relative relationship between GRK
      phosphorylation, arrestin binding, receptor sequestration and down-regulation.

PMID- 9921286
TI  - Fluorescent ligands for studying neuropeptide receptors by confocal microscopy.
AB  - This paper reviews the use of confocal microscopy as it pertains to the
      identification of G-protein coupled receptors and the study of their dynamic
      properties in cell cultures and in mammalian brain following their tagging with
      specific fluorescent ligands. Principles that should guide the choice of suitable
      ligands and fluorophores are discussed. Examples are provided from the work
      carried out in the authors' laboratory using custom synthetized fluoresceinylated
      or BODIPY-tagged bioactive peptides. The results show that confocal microscopic
      detection of specifically bound fluorescent ligands permits high resolution
      appraisal of neuropeptide receptor distribution both in cell culture and in brain
      sections. Within the framework of time course experiments, it also allows for a
      dynamic assessment of the internalization and subsequent intracellular
      trafficking of bound fluorescent molecules. Thus, it was found that neurotensin,
      somatostatin and mu- and delta-selective opioid peptides are internalized in a
      receptor-dependent fashion and according to receptor-specific patterns into their
      target cells. In the case of neurotensin, this internalization process was found
      to be clathrin-mediated, to proceed through classical endosomal pathways and, in
      neurons, to result in a mobilization of newly formed endosomes from neural
      processes to nerve cell bodies and from the periphery of cell bodies towards the
      perinuclear zone. These mechanisms are likely to play an important role for
      ligand inactivation, receptor regulation and perhaps also transmembrane
      signaling.

PMID- 9921287
TI  - Use of fluorescent probes to follow membrane traffic in nerve terminals.
AB  - Optical tracers in conjunction with fluorescence microscopy have become widely
      used to follow the movement of synaptic vesicles in nerve terminals. The present
      review discusses the use of these optical methods to understand the regulation of
      exocytosis and endocytosis of synaptic vesicles. The maintenance of
      neurotransmission depends on the constant recycling of synaptic vesicles and
      important insights have been gained by visualization of vesicles with the vital
      dye FM1-43. A number of questions related to the control of recycling of synaptic
      vesicles by prolonged stimulation and the role of calcium to control membrane
      internalization are now being addressed. It is expected that optical monitoring
      of presynaptic activity coupled to appropriate genetic models will contribute to
      the understanding of membrane traffic in synaptic terminals.

PMID- 9921288
TI  - Lymphatic filariasis in Brazilian urban area (Maceio, Alagoas).
AB  - A cross-sectional survey conducted among evening students was used to determine
      the prevalence of Wuchereria bancrofti infection in Maceio, capital of the State
      of Alagoas, northeast Brazil. A single thick-blood smear was used, being
      collected between 10 p.m. and 12 a.m. From a total of 29,551 students enrolled at
      evening elementary schools in the 33 city sectors, 16,569 (56.4%) were random
      selected for inclusion in the study. From those, 10,857 (65.5%) were interviewed
      and examined and 73 (0.7%) were found to have microfilaraemia. Autochthonous W.
      bancrofti carriers live in 10 of the 33 city sectors, suggesting a focal
      distribution. Moreover, 84% of infections were diagnosed among 29% of all
      students examined, inhabiting three contiguous sectors at the city central area,
      presenting infection rates up to 5.3%. Students living in city sectors with
      prevalence of microfilariae carriers greater than 1% were found to have a higher
      risk for infection when compared to students from the rest of the town [Relative
      Odds (RO) 12.8, 95% CI 6.7-25.1]. Eleven positive individuals from non endemic
      areas were living in Maceio for more than 10 years; time of residence in the area
      was a major risk factor for infection among students not born in the region (p <
      0.01). Regarding sex, male students presented a higher proportion of positive (RO
      1.7, 95% CI 1.1-2.9).

PMID- 9921289
TI  - An investigation on the ecology of Triatoma vitticeps (Stal, 1859) and its
      possible role in the transmission of Trypanosoma cruzi, in the locality of
      Triunfo, Santa Maria Madalena municipal district, state of Rio de Janeiro,
      Brazil.
AB  - From January 1989 to April 1995, 465 specimens of Triatoma vitticeps were
      collected in the locality of Triunfo, 2nd District of Santa Maria Madalena
      municipal district, State of Rio de Janeiro. The bugs were found indoors by local
      residents with predominance of adults. The flight activity was high in hot months
      when the incidence in the domicile also increased. Two hundred and two bugs (111
      alive and 91 dead) were examined for Trypanosoma cruzi infection. This was
      detected in 31 of the dead bugs (34%) and 88 (79%) of the live bugs examined.
      With a view to investigate the possible vertebrate hosts of the T. cruzi
      isolates, the blood of 122 mammals was examined through Giemsa-stained smears,
      hemocultures and xenodiagnosis. T. cruzi was detected in three specimens of
      Didelphis marsupialis and T. (M.) theileri was detected in one specimen of Bos
      taurus. The parasites were isolated from triatomine feces, xenoculture and
      hemoculture. No evidence of human infection was detected in 58 inhabitants
      examined, as evaluated by indirect imunofluorescence technique using T. cruzi
      epimastigotes as antigens. These results show that T. vitticeps is still a
      sylvatic species although nymphs have been found inside the domicile. Thus, an
      epidemiological vigilance is necessary to know the behaviour of this species
      following the continuous modifications promoted by the presence of man.

PMID- 9921290
TI  - Interrelationship between ectoparasites and wild rodents from Tijucas do Sul,
      state of Parana, Brazil.
AB  - Sixteen species of ectoparasites were collected from 50 wild rodents, from August
      1990 to August 1991, in an area of Araucaria augustifolia forest, in the
      municipality of Tijucas do Sul, State of Parana, Brazil. Ectoparasites infested
      98% of the rodents, with the highest indices of infestation found in the drycool
      season. Species that occurred in single or multiple infestations were recorded.
      Ectoparasite/host associations were significant (p < 0.01) for Gigantolaelaps
      wolffsohni/Oryzomys nigripes, Polygenis pradoi/Oxymycterus sp. and Amblyopinus
      sp./Oxymycterus sp. The following represent new host records: Polygenis
      (Polygenis) tripus from Akodon serrensis and Hoplopleura sciuricola from Sciurus
      aestuans. New geographic records are given for two species of flea and one
      sucking lice.

PMID- 9921291
TI  - Seroprevalence of Trypanosoma cruzi infection in students at the seven-fourteen
      age range, Londrina, PR, Brazil, in 1995.
AB  - Seropositivity for Chagas disease was evaluated in 834 children aged between 7
      and 14 from the Municipal Teaching System in the district of Londrina, State of
      Parana. A seroprevalence rate of 0.1% was found through the use of an indirect
      immunofluorescent test and an enzyme-linked immunosorbent assay. This low rate of
      seroprevalence provides evidence that the vectorial transmission of Chagas
      disease has been eliminated in Londrina. The main reason for the elimination of
      vectorial transmission of Trypanosoma cruzi infection, as evaluated by
      serological tests, may be a remarkable change in the economic structure of the
      northern region of Parana in the 1960's. At that time coffee production was
      almost completely replaced by soy beans, wheat and grazing in the rural areas.
      This change deeply affected the rural ecology and caused an exodus of the
      population from rural to urban areas as well as a decrease in the total number of
      the population of that region. The measures introduced for controlling the
      disease through the Program of Chagas Disease Control established by the Fundacao
      Nacional de Saude of the Brazilian Ministry of Health, certainly, had a positive
      impact on the reduction of American trypanosomiasis prevalence in the area under
      study. However, it does not seem that this was the most relevant factor
      responsible for the elimination of vectorial transmission of Chagas disease in
      Londrina.

PMID- 9921292
TI  - Soil contamination and human infection by Toxocara sp. in the urban area of Lima,
      Peru.

PMID- 9921294
TI  - Cosmocerca parva Travassos, 1925 (Nematoda: Cosmocercidae) in toads from
      Argentina.

PMID- 9921293
TI  - Further evidence of humans as source of Leishmania viannia for sandflies.

PMID- 9921295
TI  - Isoenzymatic characterization of Colombian strains of Trypanosoma cruzi.

PMID- 9921296
TI  - Eimeria minasensis n. sp. (Apicomplexa: Eimeriidae) in the domestic goat Capra
      hircus, from Brazil.
AB  - Eimeria minasensis n. sp. is described in the domestic goat Capra hircus from
      Brazil. Oocysts ellipsoidal are 35 x 24.5 (32-37.7 x 20.9-27.9) microns.
      Sporocysts elongate-ellipsoid are 15.2 x 9 (12.3-18.4 x 7.8-10.2) microns, with a
      Stieda body at the narrow end. Oocyst wall smooth and bilayered; outer layer
      about 1.2 (0.8-1.6) microns and colorless; inner layer about 0.5 (0.4-0.8) micron
      and dark-brown. Micropyle, a mound-shaped micropylar cap 1.6 x 8.9 (0.8-2 x 7
      10.2) easily dislodged; one or more oocyst polar granules present. Oocyst
      residuum absent. Sporocyst residuum present, composed of many scattered granules.
      Sporozoites elongate, lying lengthwise, "head to tail" in the sporocysts; one or
      two refractile globules are usually visible. Sporulation time was 120 hr at 27
      degrees C, prepatent period, 19 to 20 days and patent period 15 to 25 days.
      Gamonts, gametes and oocysts present in cecum and colon. Prevalence was 12.8%
      (6/47) in goats from Minas Gerais, Brazil.

PMID- 9921297
TI  - On a new species of Hysterothylacium (Nematoda: Anisakidae) from Cauque mauleanum
      (Pisces: Atherinidae) by brightfield and scanning electron microscopy.
AB  - Hysterothylacium geschei n. sp. (Nematoda, Anisakidae) is described from the
      intestine of Cauque mauleanum (Steindachner) (Pisces: Atherinidae) from Lake
      Panguipulli (39 degrees-43'S; 72 degrees-13'W), Chile. Eleven (78.6%) out of 14
      fish were infected, with a mean intensity (range) of 14.4 (1-55) worms. The new
      species can be differentiated from the two previously described species of
      freshwater fishes from South America by the presence of lateral alae, the number
      of caudal papillae, and the length of the spicules, oesophagus, intestinal
      caecum, distance vulva-anterior extremity and the length ratio intestinal caecum:
      ventricular appendix. From the fishes examined in Lake Panguipulli, including the
      introduced salmonid species Oncorhynchus mykiss (Walbaum) and the authochthonous
      species Basilichthys australis Eigenmann (Atherinidae) and Percichthys trucha
      (Valenciennes) (Percichthyidae), only one specimen of P. trucha was found
      parasitized by a third-stage larva of this species.

PMID- 9921298
TI  - Trypanosoma cruzi: maintenance in culture modify gene and antigenic expression of
      metacyclic trypomastigotes.
AB  - In this study we examined whether the maintenance of Trypanosoma cruzi by long
      time in axenic culture produces changes in gene expression and antigenic
      profiles. The studies were made with a Dm30L-clone from a low-virulent strain and
      a non-cloned virulent EP-strain of T. cruzi. Both parasites were maintained, for
      at least seven years, by successive alternate passage triatomine/mouse
      (triatomine condition), or by serial passage in axenic medium (culture
      condition). The comparison of the [35S]methionine metabolic labeling products of
      virulent and non-virulent parasites by 2D-SDS-PAGE, clearly indicates that the
      expression of metacyclic trypomastigotes (but not of epimastigotes) proteins have
      been altered by laboratory maintenance conditions. Western blot analysis of EP
      and Dm30L-epimastigotes using a serum anti-epimastigotes revealed that although
      most of antigens are conserved, four antigens are characteristics of triatomine
      condition parasites and three other are characteristics of culture condition
      parasites. Anti-metacyclics serum revealed significative differences in EP- and
      Dm30L-metacyclic trypomastigotes from triatomine condition. However, avirulent
      metacyclic forms were antigenically very similar. These results suggest that
      besides a possible selection of avirulent subpopulation from T. cruzi strains
      genetically heterogeneous when maintained by long time in axenic culture, changes
      in virulence might be due to post-translational modifications of the antigens
      induced by the absence of the natural alternability (vertebrate-invertebrate) in
      the life-cycle of T. cruzi.

PMID- 9921299
TI  - First report of Haematobia irritans (L.) (Diptera: Muscidae) as vector of
      Dermatobia hominis (L.jr.) (Diptera: Cuterebridae) in Minas Gerais, Brazil.

PMID- 9921300
TI  - Two new species of nematodes (Rhabditida: Diplogasteridae and Rhabditidae)
      parasites of Gryllodes laplatae (Orthoptera: Gryllidae) in Argentina.
AB  - Cephalobium magdalensis n. sp. (Rhabditida: Diplogasteridae) found in Magdalena,
      Buenos Aires, and Cruznema lincolnensis n. sp. (Rhabditida: Rhabditidae) found in
      Lincoln, Buenos Aires, parasitizing the cricket Gryllodes laplatae (Orthoptera:
      Gryllidae) are described and illustrated. C. magdalensis n. sp. is characterized
      by having the excretory pore between the pseudobulb and the basal bulb and seven
      pairs of postanal papillae in the male. C. lincolnensis n. sp. can be
      distiguished by having meanly two pairs of preanal papillae, one pair of adanal
      papillae and six pairs of postanal papillae in the male.

PMID- 9921301
TI  - Fimbriaria fasciolaris and Cloacotaenia megalops (Eucestoda, Hymenolepididae),
      cestodes from Brazilian waterfowl.
AB  - Two cestode species, Fimbriaria fasciolaris (Pallas, 1781) Frolich, 1802
      Cloacotaenia megalops (Nitzsch in Creplin, 1829) Wolffhugel, 1938 collected from
      Anas bahamensis Linne, 1758 and Amazonetta brasiliensis (Gmelin, 1758) in lagoons
      of the Marica District, State of Rio de Janeiro, Brazil, are described. This is
      the first record of F. fasciolaris parasitizing A. bahamensis. The prevalence,
      intensity of infection, and mean intensity of infection for both species are
      given. Overdispersion distribution is reported for F. fasciolaris with 535
      specimens collected in a single A. bahamensis. A key for the genera in the
      Fimbriariinae is presented. Anatomical features of F. fasciolaris and C. megalops
      are discussed.

PMID- 9921302
TI  - Numerical taxonomy of Old World Phlebotominae (Diptera: Psychodidae). 1.
      Considerations of morphological characters in the genus Phlebotomus Rondani &
      Berte 1840.
AB  - Numerical analyses (correspondence analysis, ascending hierarchical
      classification, cladistic approach) were applied to the morphological characters
      of the adults of the genus Phlebotomus Rondani & Berte 1840. They confirm the
      reliability of the classic classifications, and also redefine the taxonomic and
      phylogenetic position of certain taxa. Thus, Spelaeophlebotomus Theodor 1948.
      Idiophlebotomus Quate & Fairchild 1961 and Australophlebotomus Theodor 1948
      deserve generic rank. Among the vectors of leishmaniasis, the subgenus
      Phlebotomus Rondani & Berte 1840 is probably ancient. The results attribute an
      intermediate taxonomic and phylogenetic position to the taxa Euphlebotomus
      Theodor 1948 and Anaphlebotomus Theodor 1948, and reveal the probable artificial
      nature of the latter. The comparatively large numbers of species of subgenera
      Paraphlebotomus Theodor 1948, Synphlebotomus Theodor 1948 and, above all,
      Larroussius Nitzulescu 1931 and Adlerius Nitzulescu 1931, suggest that they are
      relatively recent. The development of adult morphological characters, the
      validity of their use in taxonomy and proposals for further studies are
      discussed.

PMID- 9921303
TI  - Numerical taxonomy of Old World Phlebotominae (Diptera: Psychodidae). 2.
      Restatement of classification upon subgeneric morphological characters.
AB  - Numerical analyses (correspondence analysis, ascending hierarchical
      classification, and cladistics) were done with morphological characters of adult
      phlebotomine sand flies. The resulting classification largely confirms that of
      classical taxonomy for supra-specific groups from the Old World, though the
      positions of some groups are adjusted. The taxa Spelaeophlebotomus Theodor 1948,
      Idiophlebotomus Quate & Fairchild 1961, Australophlebotomus Theodor 1948 and
      Chinius Leng 1987 are notably distinct from other Old World groups, particularly
      from the genus Phlebotomus Rondani & Berte 1840. Spelaeomyia Theodor 1948 and, in
      particular, Parvidens Theodor & Mesghali 1964 are clearly separate from
      Sergentomyia Franca & Parrot 1920.

PMID- 9921304
TI  - A new enzymatic variant of Leishmania (Leishmania) forattinii isolated from
      Proechimys iheringi (Rodentia, Echimydae) in Espirito Santo, Brazil.

PMID- 9921305
TI  - Overdiagnosis of intestinal amoebiasis associated to serial microscopical
      examination of faeces. Some precisions on a problem.

PMID- 9921306
TI  - Identification of mycobacteria by thin layer chromatographic analysis of mycolic
      acids and conventional biochemical method: four years of experience.
AB  - Mycolic acids analysis by thin-layer chromatography (TLC) has been employed by
      several laboratories worldwide as a method for fast identification of
      mycobacteria. This method was introduced in Brazil by our laboratory in 1992 as a
      routine identification technique. Up to the present, 861 strains isolated were
      identified by mycolic acids TLC and by standard biochemical tests; 61% out of
      these strains came as clinical samples, 4% isolated from frogs and 35% as
      environmental samples. Mycobacterium tuberculosis strains identified by classical
      methods were confirmed by their mycolic acids contents (I, III and IV). The
      method allowed earlier differentiation of M. avium complex-MAC (mycolic acids I,
      IV and VI) from M. simiae (acids I, II and IV), both with similar biochemical
      properties. The method also permitted to distinguish M. fortuitum (acids I and V)
      from M. chelonae (acids I and II), and to detect mixed mycobacterial infections
      cases as M. tuberculosis with MAC and M. fortuitum with MAC. Concluding, four
      years experience shows that mycolic acids TLC is an easy, reliable, fast and
      inexpensive method, an important tool to put together conventional mycobacteria
      identification methods.

PMID- 9921307
TI  - Basic surface properties of mononuclear cells from Didelphis marsupialis.
AB  - The electrostatic surface charge and surface tension of mononuclear
      cells/monocytes obtained from young and adult marsupials (Didelphis marsupialis)
      were investigated by using cationized ferritin and colloidal iron hydroxyde,
      whole cell electrophoresis, and measurements of contact angles. Anionic sites
      were found distributed throughout the entire investigated cell surfaces. The
      results revealed that the anionic character of the cells is given by
      electrostatic charges corresponding to -18.8 mV (cells from young animals) and 
      29.3 mV (cells from adult animals). The surface electrostatic charge decreased
      from 10 to 65.2% after treatment of the cells with each one of trypsin,
      neuraminidase and phospholipase C. The hydrophobic nature of the mononuclear cell
      surfaces studied by using the contact angle method revealed that both young and
      adult cells possess cell surfaces of high hidrofilicity since the angles formed
      with drops of saline water were 42.5 degrees and 40.8 degrees, respectively.
      Treatment of the cells with trypsin or neuraminidase rendered their surfaces more
      hydrophobic, suggesting that sialic acid-containing glycoproteins are responsible
      for most of the hydrophilicity observed in the mononuclear cell surfaces from D.
      marsupialis.

PMID- 9921308
TI  - Prostaglandin A1 inhibits replication of classical swine fever virus.
AB  - Prostaglandins (Pgs) have been shown to inhibit the replication of several DNA
      and RNA viruses. Here we report the effect of prostaglandin (PgA1) on the
      multiplication of a positive strand RNA virus, Classical Swine Fever Virus (CSFV)
      in PK15 cells. PgA1 was found to inhibit the multiplication of CSFV. At a
      concentration of 5 micrograms/ml, which was nontoxic to the cells, PgA1 inhibitis
      virus production in 99%. In PgA1 treated cells the size and number of
      characteristic Classical Swine Fever focus decreased in amount.

PMID- 9921309
TI  - The metacyclic stage-expressed meta-1 gene is conserved between Old and New World
      Leishmania species.

PMID- 9921310
TI  - Haemolymph and fat body metallo-protease associated with Enterobacter cloacae
      infection in the bloodsucking insect, Rhodnius prolixus.
AB  - Analysis of zymograms with SDS-polyacrilamide gel electrophoresis containing
      gelatin as substrate, and performed on samples of haemolymph or fat body taken
      from Rhodnius prolixus inoculated or not with Enterobacter cloacae, demonstrated
      distinct patterns of protease activities: (i) in the haemolymph two proteases
      were induced in insects inoculated with bacteria; (ii) two proteases were
      detected in the fat bodies derived from non-inoculated controls or insect
      inoculated with sterile culture medium; (iii) haemolymph and fat body had both
      the same apparent molecular weights proteases (46 and 56 kDa); and (iv) these
      enzymes were characterized as metallo-proteases. The association of these enzymes
      in Rhodnius infected with bacteria was discussed.

PMID- 9921311
TI  - Laryngeal papillomatosis in an AIDS patient.

PMID- 9921313
TI  - Selection of Beauveria bassiana and Metarhizium anisopliae isolates to control
      Triatoma infestans.
AB  - Twenty three isolates of Beauveria bassiana and 13 isolates of Metarhizium
      anisopliae were tested on third instar nymphs of Triatoma infestans, a serious
      vector of Chagas disease. Pathogenicity tests at saturated humidity showed that
      this insect is very susceptible to fungal infection. At lower relative humidity
      (50%), conditions expected in the vector microhabitat, virulence was
      significantly different among isolates. Cumulative mortality 15 days after
      treatment varied from 17.5 to 97.5%, and estimates of 50% survival time varied
      from 6 to 11 days. Maintaining lower relative humidity, four B. bassiana and two
      M. anisopliae isolates were selected for analysis of virulence at different
      conidial concentrations and temperatures. Lethal concentrations sufficient to
      kill 50% of insects (LC50) varied from 7.1 x 10(5) to 4.3 x 10(6) conidia/ml, for
      a B. bassiana isolate (CG 14) and a M. anisopliae isolate (CG 491) respectively.
      Most isolates, particularly B. bassiana isolates CG 24 and CG 306, proved to be
      more virulent at 25 and 30 degrees C, compared to 15 and 20 degrees C. The
      differential virulence at 50% humidity observed among some B. bassiana isolates
      was not correlated to phenetic groups in cluster analysis of RAPD markers. In
      fact, the B. bassiana isolates analyzed presented a high homogeneity (> 73%
      similarity).

PMID- 9921312
TI  - Zinc sulphate in the treatment of cutaneous leishmaniasis: an in vitro and animal
      study.
AB  - This study was designed to evaluate the effectiveness of zinc sulphate both in
      vitro and in an animal model against both strains of old world cutaneous
      leishmaniasis. The in vitro sensitivities of promastigotes and axenic amastigotes
      of both Leishmania major and L. tropica to zinc sulphate was determined, the LD50
      calculated and compared to the standard treatment for cutaneous leishmaniasis
      pentavalent antimony compounds. The results show that the two forms of both
      strains were sensitive to zinc sulphate and their respective LD50 were lower
      compared to the pentavalent antimony compound. Furthermore the sensitivities of
      the forms of both strains were tested using a simple slide method and compared to
      results of the standard method. To confirm this result, zinc sulphate was
      administered orally to mice infected with cutaneous leishmaniasis both
      therapeutically and prophylactically. Results showed that oral zinc sulphate was
      effective in both treatment and prophylaxis for cutaneous leishmaniasis. These
      results encourage the use of oral zinc sulphate in the treatment of cutaneous
      leishmaniasis clinically.

PMID- 9921314
TI  - Ultrastructural details of Cryptosporidium parvum development in calf intestine.
AB  - Cryptosporidium parvum and C. muris appear to be different species found in
      calves, with different oocysts size and distribution on the gastrointestinal
      tract. This work presents new images of C. parvum ultrastructure in calf
      intestine, mainly its development in nonmicrovillous cells and the presence of
      microtubular structures in the membrane enveloping the macrogamonts and immature
      oocysts.

PMID- 9921315
TI  - Experimental infection of swine by Isospora suis Biester 1934 for species
      confirmation.
AB  - A survey of Isospora suis performed in 177 faecal samples from 30 swine farms
      detected thin wall type I. suis oocysts in seven samples. This type of oocyst
      measuring 23.9 by 20.7 microns had a retracted thin wall similar to that of the
      genus Sarcocystis. This type of oocysts, isolated from four different faecal
      samples, was inoculated in four-five-days-old piglets free of contamination in
      order to verify the life cycle and pathogenicity of the species. The pigs were
      kept in individual metal cages and fed with cow milk. Daily faecal collections
      and examinations were performed until the 21st day after infection. MacMaster and
      Sheather's methods were used for oocyst counting and identification. Infected
      piglets produced yellowish-pasty diarrhoea with slight dehydration. The prepatent
      and patent periods were respectively from 6 to 9 and 3 to 10 days after
      infection. Oocyst elimination was interrupted on the 10th and 11th days after
      infection with biphasic cycles. Thin and thick wall oocysts were detected in the
      same faecal samples. Thin walls were not observed in unsporulated oocytes. The
      observations suggest that this type of oocysts could appear in specific strains
      which occur in the later stages of their development. These oocysts seem to be
      responsible for clinical and pathogenic signs of neonatal isosporosis in pigs.

PMID- 9921316
TI  - Experimental infection of Culex (Culex) quinquefasciatus and Aedes (Stegomyia)
      aegypti with Wuchereria bancrofti.
AB  - A study was conducted to determine the susceptibility of local strains of Culex
      quinquefasciatus and Aedes aegypti to infection with the strain of Wuchereria
      bancrofti that occurs in Maceio. State of Alagoas, Brazil. Cx. quinquefasciatus
      blood fed simultaneously on the same microfilariae carrier ingested more blood
      and 2-3x more microfilariae than Ae. aegypti. Survival rates of both species of
      insects living for 21 days after blood feeding on microfilaraemic patients were
      not significantly different from the survival rates of mosquitoes that blood fed
      on amicrofilaraemic individuals. W. bancrofti parasites underwent normal
      development in Cx. quinquefasciatus, with third stage larvae first being recorded
      on the 11th day post infection, and their numbers increasing thereafter.
      Development of filariae in Ae. aegypti did not proceed beyond the first larval
      stage, and there was a progressively increasing number of non-viable larvae with
      the passage of time. It is concluded that Ae. aegypti is not involved in the
      transmission of W. bancrofti in Maceio.

PMID- 9921318
TI  - Environmental determinants of infectious and parasitic diseases.
AB  - A review of the role of the environment as a determinant of infectious and
      parasitic diseases is presented. Historical considerations and the several
      environmental classifications of diseases are introduced. In a broader
      perspective the subject is analyzed in view of the emergence of the environmental
      health area, with its new paradigms. A review of epidemiological studies about
      environmental sanitation conditions and measures is presented, analyzing the
      conclusions derived from 256 studies. Finally, an epidemiological study carried
      out in Betim, Minas Gerais is briefly described, in order to illustrate the
      potentiality of this kind of study. Setting priorities of interventions regarding
      diarrhea control was the aim of this investigation. Conclusion about the role of
      this approach to optimize preventive measures for the control of infectious and
      parasitic diseases, of sound importance to the reality of the developing world,
      is stated.

PMID- 9921317
TI  - The effects of a DNA virus infection on the reproductive potential of female
      tsetse flies, Glossina morsitans centralis and Glossina morsitans morsitans
      (Diptera: Glossinidae).
AB  - Reproductive anomalies associated with the tsetse DNA virus infection in the
      female tsetse hosts, Glossina morsitans centralis Machado and Glossina morsitans
      morsitans Westwood, inoculated with the virus during the 3rd instar larval stage
      were studied and the data compared to those obtained from the control females
      injected with sterile physiological saline. Virus infected flies had
      significantly longer first and second pregnancy cycles (P < 0.0001) and produced
      pupae that were of significantly less weight in milligrams (P < 0.0001) compared
      to controls. Transmission of the virus to progeny was not absolute and only 21%
      of G. m. centralis and 48% of G. m. morsitans first progeny flies from infected
      females developed salivary gland hypertrophy as a result of transmission from
      mother to progeny. The virus infected females produced significantly fewere pupae
      compared to the controls during the experimental period (P < 0.00001).

PMID- 9921319
TI  - Effects of schistosomal mansoni infection on Calomys callosus coelom-associated
      lymphomyeloid tissue (milky spots).
AB  - Calomys callosus Rengger, 1830 (Rodentia: Cricetidae) is a mouse-like South
      American wild rodent, which is permissive to Schistosoma mansoni infection. In
      this paper we studied the effect of schistosomal infection in C. callosus
      mesenteric and omental milky spots (MS), subsidiary foci of coelom-associated
      lymphomyeloid tissue (CALT), during the acute, transitional (acute to chronic),
      and chronic phases of the infection. MS were morphologically analyzed by
      histological methods, using brightfield and confocal laser scanning microscopies.
      The MS of infected animals were mainly of lymphomyelocytic (42 to 90 days) and
      lymphoplasmacytic (160 days of infection) types and showed frequent presence of
      lymphoid follicles with germinal centers, plasmacytogenesis and plasmacytosis,
      mastocytosis, megakaryopoiesis, erythropoiesis and less pronounced eosinopoiesis.
      These results indicate that MS are a preferential site of germinal-center
      dependent and independent plasmacytogenesis, and a bone marrow-like organ,
      committed with various cellular lineages. The consequence of C. callosus MS
      reactivity for schistosomal infection is still unknown and is under
      investigation.

PMID- 9921320
TI  - Role of cytokines in the formation and downregulation of hepatic circumoval
      granulomas and hepatic fibrosis in Schistosoma mansoni-infected mice.
AB  - Schistosoma mansoni infections are associated with a strong Th2 cytokine
      response. Treatment of mice with IL-12 or anti-IL-2 or anti-IL-4 before i.v.
      injection of eggs increased IFN-gamma production and downregulated Th2 responses
      and pulmonary granuloma size. Conversely, anti-IFN-gamma antibody treatment
      increased Th2 responses and granuloma size. Similar manipulation produced less
      dramatic results in infected mice. However, sensitization of mice with eggs + IL
      12 before infection augmented the Th1 response and decreased Th2 cytokines,
      granuloma size and fibrosis. Antisera to IFN-gamma, TNF-alpha or IL-12 during IL
      12-egg immunization partly restored granuloma size and fibrosis following
      infection. Variations in the size of granulomas in acute (8 week) infections may
      be influenced primarily by the number and state of activation of T cells. In
      chronic (12-16 week) infections immunologic downmodulation proceeded normally in
      mice without functional CD8+ cells and in IFN-gamma KO mice but not in B cell KO
      (microMT) mice or in mice deficient in FcR expression in spite of the fact that
      these mice downregulated their T cell and cytokine responses. It is evident that
      the participation of cytokines in granuloma formation and regulation is
      complicated and that the mechanisms controlling both these phenomena are likely
      to involve both T cells and antibody/FcR interactions.

PMID- 9921321
TI  - Schistosomiasis control in Brazil.
AB  - In 1975 the Special Programme for Schistosomiasis Control was introduced in
      Brazil with the objective of controlling this parasitic disease in six
      northeastern states. The methodology applied varied largely from state to state,
      but was based mainly on chemotherapy, This Programme was modified about ten years
      after it beginning with the main goals including control of morbidity and the
      blockage of establishment of new foci in non-endemic areas. In two states, Bahia
      and Minas Gerais, the schistosomiasis control programme started in 1979 and 1983,
      respectively. The recently made evaluation of those two programmes is the main
      focus of this paper. It must also be pointed out, that the great majority of the
      studies performed by different researchers in Brazil, at different endemic areas,
      consistently found significant decrease on prevalence and incidence, when control
      measures are repeatedly used for several years. Significant decrease of
      hepatosplenic forms in the studied areas is well documented in Brazil. After more
      than 20 years of schistosomiasis control programmes in our country, chemotherapy
      has shown to be a very important tool for the control of morbidity and to
      decrease prevalence and incidence in endemic areas. Nevertheless, in medium and
      long terms, sanitation, water supply, sewage draining and health education seem
      to be the real tools when the aim is persistent and definitive schistosomiasis
      control.

PMID- 9921322
TI  - Microgeographical patterns of schistosomiasis and water contact behavior;
      examples from Africa and Brazil.
AB  - This paper examines the results of spatial (microgeographical) water
      contact/schistosomiasis studies in two African (Egyptian and Kenyan) and one
      Brazilian communities. All three studies used traditional cartographic and
      statistical methods but one of them employed also GIS (geographical information
      systems) tools. The advantage of GIS and their potential role in schistosomiasis
      control are briefly described. The three cases revealed considerable variation in
      the spatial distribution of water contact, transmission parameters and infection
      levels at the household and individual levels. All studies showed considerable
      variation in the prevalence and intensity of infection between households. They
      also show a variable influence of distance on water contact behavior associated
      with type of activity, age, sex, socioeconomic level, perception of water
      quality, season and availability of water in the home. Water contact behavior and
      schistosomiasis were evaluated in the Brazilian village of Nova Uniao within the
      context of water sharing between household and age/sex groups. Recommendations
      are made for further spatial studies on the transmission and control of
      schistosomiasis.

PMID- 9921323
TI  - An interactive perspective of health education for the tropical disease control:
      the schistosomiasis case.
AB  - Some municipalities in Brazil have been requesting orientation for the
      implementation of health education programs related to the control of
      schistosomiasis. This demand was based on experiences in the development of
      health education researches, strategies and materials for school-age children,
      involving the communities and secretaries of health and education. Motivated by
      this request and the recently implemented plan of health services (Unified Health
      System-Sistema Unico de Saude-SUS) that gives autonomy to the municipalities to
      utilize health resources and services in Brazil, this paper presents an
      interactive perspective of planning health education research and programs. The
      purpose of this perspective is to stimulate a reflection on the needs and actions
      of institutions and people involved in health education research and/or programs
      to obtain sustainability, commitment and effectiveness--not only in the control
      of schistosomiasis, but also in the improvement of environmental conditions,
      quality of life and personal health. This perspective comprises interaction among
      three levels related to health education programs: the decision level, the
      executive level and the beneficiary level. The needs and lines of action at each
      of these levels are discussed, as well as the ways in which they can interact
      with each other. This proposal may lead to useful interactive ways of planing,
      organizing, executing and evaluating health education research and/or program,
      not only towards the prevention and control of the disease at stake, but also to
      promote health in general.

PMID- 9921324
TI  - Epidemiology and anthropology: an integrated approach dealing with bio-socio
      cultural aspects as strategy for the control of endemic diseases.
AB  - The control of endemic diseases has not attained the desired level of
      effectiveness in spite of the use of modern efficient technologies. The classic
      interventionist approach for the control of schistosomiasis is centered on
      systemic control of the snail hosts combined to large scale medical treatment and
      is usually carried out without social preoccupation due to the assisted
      communities. It is easy to understand the interest and the ethical compromise of
      public health research while producing studies in which the biological and social
      determinants as well as the cultural components should be considered and also
      encompass the historical dimensions and symbolic representations. In face of the
      recent political decision in favor of decentralizations of health administration
      to municipal level, we suggest, in the present paper, an integrated approach for
      the epidemiological diagnosis of an endemic situation at local level. Theoretical
      and methodological aspects from both, epidemiology and anthropology are
      discussed. Epidemiological methods can be used to detect the dependent variables
      (those related to the human infection) and the independent variables
      (demographic, economic, sanitary and social). Another methodological approach of
      anthropological/ethnographic nature can be conducted in order to make an
      articulation of the knowledge on the various dimensions or determinant levels of
      the disease. Mutual comprehension, between researchers and the people under
      investigation, on the dynamic transmission process would be relevant for a joint
      construction, at local level, of programmed actions for the control of endemic
      diseases. This would extend reflections on the health/disease process as a whole.

PMID- 9921325
TI  - The stabilizing effects of the acquired immunity on the schistosomiasis
      transmission modeling--the sensitivity analysis.
AB  - A mathematical model is proposed to analyze the effects of acquired immunity on
      the transmission of schistosomiasis in the human host. From this model the
      prevalence curve dependent on four parameters can be obtained. These parameters
      were estimated fitting the data by the maximum likelihood method. The model
      showed a good retrieving capacity of real data from two endemic areas of
      schistosomiasis: Touros, Brazil (Schistosoma mansoni) and Misungwi, Tanzania (S.
      haematobium). Also, the average worm burden per person and the dispersion of
      parasite per person in the community can be obtained from the model. In this
      paper, the stabilizing effects of the acquired immunity assumption in the model
      are assessed in terms of the epidemiological variables as follows. Regarded to
      the prevalence curve, we calculate the confidence interval, and related to the
      average worm burden and the worm dispersion in the community, the sensitivity
      analysis (the range of the variation) of both variables with respect to their
      parameters is performed.

PMID- 9921326
TI  - Different approaches to modelling the cost-effectiveness of schistosomiasis
      control.
AB  - This paper reviews three different approaches to modelling the cost-effectiveness
      of schistosomiasis control. Although these approaches vary in their assessment of
      costs, the major focus of the paper is on the evaluation of effectiveness. The
      first model presented is a static economic model which assesses effectiveness in
      terms of the proportion of cases cured. This model is important in highlighting
      that the optimal choice of chemotherapy regime depends critically on the level of
      budget constraint, the unit costs of screening and treatment, the rates of
      compliance with screening and chemotherapy and the prevalence of infection. The
      limitations of this approach is that it models the cost-effectiveness of only one
      cycle of treatment, and effectiveness reflects only the immediate impact of
      treatment. The second model presented is a prevalence-based dynamic model which
      links prevalence rates from one year to the next, and assesses effectiveness as
      the proportion of cases prevented. This model was important as it introduced the
      concept of measuring the long-term impact of control by using a transmission
      model which can assess reduction in infection through time, but is limited to
      assessing the impact only on the prevalence of infection. The third approach
      presented is a theoretical framework which describes the dynamic relationships
      between infection and morbidity, and which assesses effectiveness in terms of
      case-years prevented of infection and morbidity. The use of this model in
      assessing the cost-effectiveness of age-targeted treatment in controlling
      Schistosoma mansoni is explored in detail, with respect to varying frequencies of
      treatment and the interaction between drug price and drug efficacy.

PMID- 9921327
TI  - The tegument of Schistosoma mansoni: genes, antigens and the host-parasite
      relationship.

PMID- 9921328
TI  - Glutathione S-transferases of 28kDa as major vaccine candidates against
      schistosomiasis.
AB  - For the development of vaccine strategies to generate efficient protection
      against chronic infections such as parasitic diseases, and more precisely
      schistosomiasis, controlling pathology could be more relevant than controlling
      the infection itself. Such strategies, motivated by the need for a cost-effective
      complement to existing control measures, should focus on parasite molecules
      involved in fecundity, because in metazoan parasite infections pathology is
      usually linked to the output of viable eggs. In numerous animal models,
      vaccination with glutathione S-transferases of 28kDa has been shown to generate
      an immune response strongly limiting the worm fecundity, in addition to the
      reduction of the parasite burden. Recent data on acquired immunity directed to
      28GST in infected human populations, and new development to draw adapted vaccine
      formulations, are presented.

PMID- 9921329
TI  - Schistosomiasis vaccine development: progress and prospects.
AB  - The undisputed, worldwide success of chemotherapy notwithstanding,
      schistosomiasis continues to defy control efforts in as much rapid reinfection
      demands repeated treatment, sometimes as often as once a year. There is thus a
      need for a complementary tool with effect for the longer term, notably a vaccine.
      International efforts in this direction have been ongoing for several decades
      but, until the recombinant DNA techniques were introduced, antigen production
      remained an insurmountable bottleneck. Although animal experiments have been
      highly productive and are still much needed, they probably do not reflect the
      human situation adequately and real progress can not be expected until more is
      known about human immune responses to schistosome infection. It is well-known
      that irradiated cercariae consistently produce high levels of protection in
      experimental animals but, for various reasons, this proof of principle cannot be
      directly exploited. Research has instead been focussed on the identification and
      testing of specific schistosome antigens. This work has been quite successful and
      is already at the stage where clinical trials are called for. Preliminary results
      from coordinated in vitro laboratory and field epidemiological studies regarding
      the protective potential of several antigens support the initiation of such
      trials. A series of meetings, organized earlier this year in Cairo, Egypt,
      reviewed recent progress, selected suitable vaccine candidates and made firm
      recommendations for future action including pledging support for large-scale
      production according to good manufacturing practice (GMP) and Phase I trials.
      Scientists at the American Centers for Disease Control and Prevention (CDC) have
      drawn up a detailed research plan. The major financial support will come from
      USAID, Cairo, which has established a scientific advisory group of Egyptian
      scientists and representatives from current and previous international donors
      such as WHO, NIAID, the European Union and the Edna McConnell Clark Foundation.

PMID- 9921330
TI  - Genetic variability and identification of the intermediate snail hosts of
      Schistosoma mansoni.
AB  - Studies based on shell or reproductive organ morphology and genetic
      considerations suggest extensive intraspecific variation in Biomphalaria snails.
      The high variability at the morphological and genetic levels, as well as the
      small size of some specimens and similarities between species complicate the
      correct identification of these snails. Here we review our work using methods
      based on polymerase chain reaction (PCR) amplification for analysis of genetic
      variation and identification of Biomphalaria snails from Brazil, Argentina,
      Uruguay and Paraguay. Arbitrarily primed-PCR revealed that the genome of B.
      glabrata exhibits a remarkable degree of intraspecific polymorphism. Low
      stringency-PCR using primers for 18S rRNA permitted the identification of B.
      glabrata, B. tenagophila and B. occidentalis. The study of individuals obtained
      from geographically distinct populations exhibits significant intraspecific DNA
      polymorphism, however, specimens from the same species, exhibit some species
      specific LSPs. We also showed that PCR-restriction fragment of length
      polymorphism of the internal transcribed spacer region of Biomphalaria rDNA,
      using Ddel permits the differentiation of the three intermediate hosts of
      Schistosoma mansoni. the molecular biological techniques used in our studies are
      very useful for the generation of new knowledge concerning the systematics and
      population genetics of Biomphalaria snails.

PMID- 9921331
TI  - Molecular characterisation of intermediate snail hosts and the search for
      resistance genes.
AB  - The relationship between schistosomes and their intermediate hosts is an
      extremely intricate one with strains and species of the parasite depending on
      particular species of snail, which in turn may vary in their susceptibility to
      the parasites. In order to gain a better understanding of the epidemiology of the
      disease we have been investigating the use of molecular markers for snail
      identification and for studying host-parasite relationships. In this paper we
      will draw on examples concerning schistosomiasis in West and East Africa to
      illustrate how a molecular analysis can be used as part of a "total evidence"
      approach to characterisation of Bulinus species and provide insights into
      parasite transmission. Particular emphasis is given to ribosomal RNA genes
      (rRNA), random amplified polymorphic DNA (RAPDs) and the mitochondrial gene
      cytochrome oxidase I (COI). Snails resistant to infection occur naturally and
      there is a genetic basis for this resistance. In Biomphalaria glabrata resistance
      to Schistosoma mansoni is known to be a polygenic trait and we have initiated a
      preliminary search for snail genomic regions linked to, or involved in,
      resistance by using a RAPD based approach in conjunction with progeny pooling
      methods. We are currently characterising a variety of STSs, (sequence tagged
      sites) associated with resistance. These can be used for local linkage and
      interval mapping to define genomic regions associated with the resistance trait.
      The development of such markers into simple dot-blot or specific PCR-based assays
      may have a direct and practical application for the identification of resistant
      snails in natural populations.

PMID- 9921332
TI  - Histopathologic features associated with susceptibility and resistance of
      Biomphalaria snails to infection with Schistosoma mansoni.
AB  - Resistance and susceptibility of Biomphalaria snails to Schistosoma mansoni
      sporocysts occur in different degrees. Histopathology reflects these differences.
      In a state of tolerance numerous sporocysts in different stages of
      differentiation are seen in the absence of host tissue reaction. However
      extensive diffuse and focal proliferation of amebocytes with sequestration and
      destruction of many parasitic structures appear in resistant snails. Some snails
      are totally resistant and when exposed to infecting miracidia may never eliminate
      cercarie. Sequential histopathological examination has revealed that in such
      cases the infected miracidia are destroyed a few minutes to 24 hr after
      penetration in the snail. However, B. glabrata that were exposed to S. mansoni
      miracidia and three months later failed to shed cercariae, exhibited focal and
      diffuse proliferation of amebocytes in many organs in the absence of pasitic
      structures. These lesions were similar to those observed in resistant snails that
      were still eliminating a few cercariae, with the difference that no recognizable
      sporocystic structures or remnants were present. Histological investigation
      carried out in similarly resistant B. tenagophila and B. straminea presented
      essentially normal histologic structures. Only occasionally a few focal
      proliferative (granulomatous) amebocytic reactions were seen in ovotestis and in
      the tubular portion of the kidney. Probably, there are two types of reactions to
      miracidium presented by totally resistant snails: one would implicate the
      immediate destruction of the miracidium leaving no traces in the tissues; the
      other involving late reactions that seem to completely destroy invading
      sporocysts and leave histological changes.

PMID- 9921333
TI  - Age-related worm load and worm fecundity patterns in human populations, as
      indicated by schistosome circulating antigens.
AB  - Recently, our group determined the relationship between serum CAA levels and
      fecal egg counts in two foci with very intense Schistosoma mansoni transmission:
      Maniema (Zaire), an area endemic for S. mansoni since several decades, and Ndombo
      (Senegal), where transmission has only been established since a few years. The
      objective was to study and compare age-related worm load and worm fecundity
      patterns in these two different endemic settings. Here, we will summarize the
      most important findings and conclusions of this study.

PMID- 9921334
TI  - Genital manifestations of schistosomiasis mansoni in women: important but
      neglected.
AB  - Egg-induced lesions in the upper and the lower female reproductive tract are
      important complications of the infection with Schistosoma mansoni. The
      understanding of the pathophysiology and pathology of genital lesions is only
      rudimentary, simple and reliable diagnostic tools are not at hand,
      epidemiological data do not exist and how to treat best the women affected, is
      not known. In view of recent advances in the understanding of genital lesions
      induced by S. haematobium the existing literature is critically analyzed and
      possible consequences of female genital schistosomiasis are outlined. We estimate
      that 6 to 27% girls and women with intestinal schistosomiasis, at least
      temporarily, suffer from pathology induced by eggs sequestered somewhere in their
      genital organs. This is a matter of concern and warrants more research into the
      epidemiology, pathology, diagnosis and therapy of this disease entity.

PMID- 9921335
TI  - Schistosomiasis and associated infections.
AB  - In hospital-based series viral hepatitis B has been frequently described in
      association with schistosomiasis whilst in field-based studies the association
      has not been confirmed. The association between schistosomiasis and Salmonella
      bacteraemia has been well documented. More recently, acute schistosomiasis has
      been shown to be a facilitating factor in the genesis of pyogenic liver abscesses
      caused by Staphylococcus aureus. New evidences indicate an interaction between
      the acquired immunodeficiency syndrome (AIDS) and schistosomiasis. In this paper,
      data on the association of schistosomiasis with other infections are updated.

PMID- 9921336
TI  - Histoarchitecture of schistosomal granuloma development and involution:
      morphogenetic and biomechanical approaches.
AB  - The authors present morphogenetic and biomechanical approaches on the concept of
      the Schistosoma mansoni granulomas, considering them as organoid structures that
      depend on cellular adhesion and sorting, forming rearrangement into hierarchical
      concentric layers, creating tension-dependent structures, aiming to acquire round
      form, since this is the minimal energy form, in which opposing forces pull in
      equally from all directions and are in balance. From the morphogenetic point of
      view, the granulomas function as little organs, presenting maturative and
      involutional stages in their development with final disappearance (pre
      granulomatous stages, subdivided in: weakly and/or initial reactive and
      exudative; granulomatous stages: exudative-productive, productive and
      involutional). A model for the development of granulomas was suggested, according
      to the following stages: encapsulating, focal histolysis, fiber production,
      orientation and compacting and involution and disintegration. The authors
      concluded that schistosomal granuloma is not a tangled web of individual cells
      and fibers, but an organized structure composed by host and parasite components,
      which is not formed to attack the miracidia, but functions as an hybrid interface
      between two different phylogenetic beings.

PMID- 9921337
TI  - Portal veins of mice infected with Schistosoma mansoni exhibit an increased
      reactivity to 5-hydroxytryptamine.
AB  - In chronic severe infection with Schistosoma mansoni, portal hypertension and
      related vascular alterations usually develop as a consequence of granulomatous
      response to eggs. In order to investigate a putative direct effect of worms on
      the reactivity of their host portal vein, mice infected only with male worms were
      used in the present study. An higher reactivity to 5-hydroxytryptamine (5-HT)
      characterized by an increase in the maximal contraction and sensitivity was
      observed in portal vein from infected mice compared to healthy mice. Blockade of
      NO-synthase with l-NAME induced a small increase in 5-HT potency in portal vein
      from non-infected mice without changing the amplitude of the contractions,
      whereas it did not alter the reactivity of veins from infected mice. The present
      results show that unisexual infection of mice with male S. mansoni increased the
      reactivity of the portal vein to 5-HT which seems to be partially related to an
      alteration in the nitric oxide release by endothelium.

PMID- 9921338
TI  - Use of synthetic peptides derived from adult worm proteins of Schistosoma
      mansoni, in the diagnosis of schistosomiasis.

PMID- 9921339
TI  - The spleen is an important site of T cell activation during human hepatosplenic
      schistosomiasis.
AB  - We have undertaken a comparative immunophenotypic study of spleen cells from
      hepatosplenic patients (HS) and uninfected individuals (NOR) using flow
      cytometry. Our data did not show any significant differences in the mean
      percentage of T-cells and B-cells between the two groups. Analysis of activated T
      cells demonstrated that HS present an increased percentage of CD3+HLA-DR+
      splenocytes in comparison to NOR. Analysis of T-cell subsets demonstrated a
      significant increase on the percentage of both activated CD4+ T-splenocytes and
      CD8+ cells in HS. We did not find any difference in the mean percentage of CD28+
      T-cells. Analysis of the B-cell compartment did not show any difference on the
      percentage of B1-splenocytes. However, the spleen seems to be an important
      reservoir/source for B1 lymphocytes during hepatosplenic disease, since after
      splenectomy we found a decreased the percentage of circulating B1-lymphocytes. We
      observed an increase on the percentage of CD2+ CD3- lymphocytes in the spleen of
      HS suggesting that the loss of CD3 by activated T-cells or the expansion of NK
      cells might play a role in the development/maintenance of splenomegaly.

PMID- 9921340
TI  - Biochemical characterization of cathepsin D from adult Schistosoma mansoni worms.

PMID- 9921342
TI  - The myoglobin and the hemoglobin of Biomphalaria glabrata, an evidence of gene
      duplications.

PMID- 9921341
TI  - Molecular study of similar Biomphalaria species.

PMID- 9921343
TI  - Preliminary results on the regulatory role of IFN-gamma and IL-10 human
      schistosomiasis mansoni.

PMID- 9921344
TI  - Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm
      antigenic preparation, affects nitric oxide production by murine spleen cells.
AB  - Nitric oxide (NO) is an important effector molecule involved in immune regulation
      and defense. NO produced by cytokine-activated macrophages was reported to be
      cytotoxic against the helminth Schistosoma mansoni. Identification and
      characterization of S. mansoni antigens that can provide protective immunity is
      crucial for understanding the complex immunoregulatory events that modulate the
      immune response in schistosomiasis. It is, then, essential to have available
      defined, purified parasite antigens. Previous work by our laboratory identified a
      fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named
      PIII, able to elicit significant in vitro cell proliferation and at the same time
      lower in vitro and in vivo granuloma formation when compared either to SEA
      (soluble egg antigen) or to SWAP. In the present work we report the effect of
      different in vivo trials with mice on their spleen cells ability to produce NO.
      We demonstrate that PIII-immunization is able to significantly increase NO
      production by spleen cells after in vitro stimulation with LPS. These data
      suggest a possible role for NO on the protective immunity induced by PIII.

PMID- 9921345
TI  - (Ca(2+)-Mg2+)ATPase in Schistosoma mansoni: evidence for heterogeneity and
      resistance to praziquantel.

PMID- 9921346
TI  - IgE and IgG4 antibodies in subjects reinfected with Schistosoma mansoni in an
      endemic area of northeast Brazil.

PMID- 9921347
TI  - Protective immunity induced in mice by F8.1 and F8.2 antigens purified from
      Schistosoma mansoni eggs.
AB  - Schistosoma mansoni soluble egg antigens (SEA) were fractionated by isoelectric
      focusing, resulting in 20 components, characterized by pH, absorbance and protein
      concentration. The higher absorbance fractions were submitted to electrophoresis,
      and fraction 8 (F8) presented a specific pattern of bands on its isoelectric
      point. Protein 3 was observed only on F8, and so, it was utilized to rabbit
      immunization, in order to evaluate its capacity of inducing protective immunity.
      IgG antibodies from rabbit anti-F8 serum were coupled to Sepharose, and used to
      obtain the specific antigen by affinity chromatography. This antigen, submitted
      to electrophoresis, presented two proteic bands (F8.1 and F8.2), which were
      transferred to nitrocellulose membrane (PVDF) and sequenciated. The homology of
      F8.2 to known proteins was determined using the Basic Local Alignment Search Tool
      program (BLASTp). Significant homologies were obtained for the rabbit cytosolic
      Ca2+ uptake inhibitor, and for the bird a1-proteinase inhibitor. Immunization of
      mice with F8.1 and F8.2, in the presence of Corynebacterium parvum and Al(OH)3 as
      adjuvant, induced a significant protection degree against challenge infection, as
      observed by the decrease on worm burden recovered from portal system.

PMID- 9921348
TI  - Induction of protective immunity against Schistosoma mansoni infection by
      antigens purified from PIII, a fraction of adult worm, associated to the
      downregulation of granuloma formation.
AB  - This study was performed in order to define Schistosoma mansoni antigens able to
      function as modulator agents in BALB/c mice granulomatous hypersensitivity to
      parasite egg. The antigens P-24, P-35 and P-97 were purified by affinity
      chromatography from a fraction of S. mansoni adult worm antigenic preparation,
      denominated PIII, involved in the inhibition of granulomatous response to eggs.
      Immunization of mice with these antigens, in the presence of Corynebacterium
      parvum and Al(OH)3 as adjuvant, induced a significant protection degree against
      challenge infection, as observed by the decrease on worm burden recovered from
      portal system. In vitro blastogenesis assays revealed that purified antigens were
      able to induce significant proliferation of spleen cells from S. mansoni-infected
      mice. This protection was correlated to significant decrease in granuloma size
      induced by PIII. From these results, we concluded that PIII preparation contains
      antigens capable of mediating protective anti-parasite immunity and down
      regulating granulomatous hypersensitivity to S. mansoni eggs.

PMID- 9921349
TI  - Influence of dietary n-6 and n-3 lipids upon the development of pulmonary
      granulomas induced by Schistosoma mansoni eggs.

PMID- 9921351
TI  - Lactate dehydrogenase: sequence and analysis of its expression during the life
      cycle of Schistosoma mansoni.

PMID- 9921350
TI  - A long-term intake of a protein hydrolysate seems to increase the risk of
      encephalopathy in mice infected with Schistosoma mansoni.
AB  - Previous investigations showed that Schistosoma mansoni infection aggravates
      protein malabsorption in undernourished mice and this can be reverted by
      administration of casein hydrolysate. The present study was undertaken to
      evaluate the effects of ingestion of casein hydrolysate for long periods. Albino
      Swiss mice were divided into eight groups. Diets contained 5% (undernourished) or
      20% (controls) casein levels. For each group there were sub-groups ingesting
      whole or hydrolysed casein for 12 weeks. Infection with S. mansoni developed in
      half of the animals under each diet. All undernourished mice developed
      malabsorption. Low albuminemia was detected in infected animals independently of
      the protein level in the diet. However, albuminemia was lower in infected
      controls than in undernourished non-infected mice, suggesting a deficient liver
      protein synthesis. Infected mice fed on a 20% protein hydrolysed diet exhibited
      low weight gain and high mortality rates. On the other hand, non-infected mice
      ingesting the same diet had the highest body weights. We are investigating the
      hypothesis that infected mice, even when fed normal diets, are unable to
      metabolise large amounts of amino acids due to the liver lesions related to
      schistosomiasis and as a result die of hepatic coma. In some of them, the
      excessive accumulation of ammonia in the blood enhances the outcome of an
      encephalopathy.

PMID- 9921352
TI  - Sequencing and expression analysis of a Schistosoma mansoni gene homologue to a
      Drosophila gene involved in germ plasm assembly.

PMID- 9921353
TI  - Characterization of an abundant Schistosoma mansoni transcript with no homologs
      in the databases.

PMID- 9921354
TI  - Transcription levels of two actin genes (SmAct and SmAct2), cytochrome C oxidase
      subunit II (SmCOXII), triosephosphate isomerase (TPI), and a putative translation
      regulatory protein EIF-5 during the first seven days of in vitro development of
      Schistosoma mansoni schistosomula.

PMID- 9921355
TI  - Molecular identification of similar species of the genus Biomphalaria (Mollusca:
      Planorbidae) determined by a polymerase chain reaction-restriction fragment
      length polymorphism.
AB  - The freshwater snails Biomphalaria straminea, B. intermedia, B. kuhniana and B.
      peregrina, are morphologically similar; based on this similarity the first three
      species were therefore grouped in the complex B. straminea. The morphological
      identification of these species is based on characters such as vaginal wrinkling,
      relation between prepuce: penial sheath:deferens vas and number of muscle layers
      in the penis wall. In this study the polymerase chain reaction restriction
      fragment length polymorphism technique was used for molecular identification of
      these molluscs. This technique is based on the amplification of the internal
      transcribed spacer regions ITS1 e ITS2 of the ribosomal RNA gene and subsequent
      digestion of these fragments by restriction enzymes. Six enzymes were tested: Dde
      I, Mn1 I, Hae III, Rsa I, Hpa II e Alu I. The restriction patterns obtained with
      DdeI presented the best profile for separation of the four species of
      Biomphalaria. The profiles obtained with all the enzymes were used to estimate
      the genetic distances among the species through analysis of common banding
      patterns.

PMID- 9921356
TI  - Possible hybridization of Brazilian planorbid snails and its importance in
      population dynamics.
AB  - This study focuses on the possibility of experimental hybridization among host
      snail species for Schistosoma mansoni in Brazil, with morphological
      characterization of the hybrids found. By using albinism as a genetic marker,
      intraspecific crossbreedings were performed between two strains of each species
      involved, in addition to interspecific crossbreedings; the only viable
      crossbreeding was between pigmented Biomphalaria glabrata (Paulista, PE) and
      albino B. tenagophila (Joinville, SC), with the formation of F1 and F2
      generations. All offspring in F1 displayed black eyes and a renal ridge on the
      mantle, while F2 displayed dissociated morphological traits. With regard to
      reproduction, F1 was more efficient than F2. The experiment's results suggest
      post-zygotic reproductive isolation.

PMID- 9921357
TI  - A survey of freshwater gastropods in the Microrregiao Serrana of the state of Rio
      de Janeiro, Brazil.

PMID- 9921358
TI  - Effects of Euphorbia milii latex on Schistosoma mansoni eggs, miracidia and
      cercariae.

PMID- 9921359
TI  - Effect of Bayluscide WP 70 on the kinetic behaviour of Biomphalaria straminea in
      laboratory conditions.

PMID- 9921360
TI  - Morbidity of schistosomiasis in an endemic area of the northeast of the state of
      Minas Gerais in Brazil: a clinical and sonographic study.

PMID- 9921361
TI  - Splenic palpation for the evaluation of morbidity due to schistosomiasis mansoni.
AB  - This study was undertaken to determine the accuracy of splenic palpation for the
      diagnosis of splenomegaly, and to determine whether the frequency of individuals
      with a palpable spleen in an endemic area can be considered as an index of
      morbidity of schistosomiasis. For the clinical diagnosis of splenomegaly, two
      criteria have been tested: (A) presence of a palpable spleen and (B) presence of
      a palpable spleen whose border could be felt more than 4 cm below the costal
      margin. In an area of high prevalence of the disease (66.3%) 285 individuals aged
      18 years or more have been submitted to abdominal ultrasonography and physical
      examination. Splenomegaly was defined as a splenic length greater than 120 mm by
      ultrasound and the sensitivity, specificity, positive and negative predictive
      values of criterion A were 72.2%, 90.5%, 35.1% and 97.8%. The values for
      criterion B were 27.8%, 98%, 50% and 95%, respectively. In an non endemic area,
      517 individuals were submitted to the same protocol and 22 individuals had a
      palpable spleen, but no patient fulfilled criterion B for splenomegaly, and only
      one met the ultrasonographic criterion for splenomegaly. The authors concluded
      that abdominal palpation is a poor method for the diagnosis of splenomegaly.

PMID- 9921362
TI  - Chronic carriers of hepatitis B surface antigen in an endemic area for
      schistosomiasis mansoni in Brazil.
AB  - Data on the association of schistosomiasis and hepatitis B in field-based studies
      are scarce. Two areas have been selected for this study: i) Queixadinha, endemic
      for schistosomiasis, with a population of 693 individuals, and ii) Capao, a
      control non-endemic area, with 515 inhabitants. Sera of all individuals in both
      areas were tested for hepatitis B infection, yearly, from 1994 to 1997. In the
      first area hepatitis B was found in 32.1% of children up to one year old and
      reached a peak of 68.7% in the age range of 15 to 19 years. In the control area
      the prevalence of hepatitis B was under 5% up to 19 years of age and the highest
      prevalence was observed in adults over 45. HBsAg was detected in 9.4% of the
      individuals living in the endemic area for schistosomiasis and in 1.4% of the
      controls (OR = 4.98; 95% CI = 3.7-6.7). The index of chronicity of HBsAg was not
      statistically different in the studied areas (8.1% x 7.3%; OR = 1.09; 95% CI =
      0.42-3.03), nor was it different for people with and without schistosomiasis in
      Queixadinha (8.7% x 7.0%). We conclude that the Schistosoma mansoni infection has
      not altered the course of hepatitis B in the studied area.

PMID- 9921363
TI  - Prognosis of schistosomiasis mansoni patients infected with hepatitis B virus.
AB  - A clinical study on the evolution of patients with schistosomiasis mansoni has
      been conducted since 1983 at the outpatient clinic of the Infectious and
      Parasitic Disease Service in the Clementino Fraga Filho University Hospital in
      Rio de Janeiro, Brazil, comparing prevalence of positive tests for HBsAg, anti
      HBsAg, and anti-HBc among patients infected with Schistosoma mansoni coming from
      various regions of Brazil and with different clinical forms of the disease. A non
      significant predominance of HBsAg, anti-HBsAg, and anti-HBc was detected among
      patients with the hepatosplenic form of schistosomiasis, who presented a more
      severe clinical evolution with a higher frequency of hematemesis and/or melena,
      in addition to the development of macronodular cirrhosis and a worse prognosis as
      compared to patients with the toxemic form, schistosomiasis-infection and the
      hepatointestinal form.

PMID- 9921364
TI  - Schistosomiasis control based on repeated chemotherapy in a rural village of the
      sugar-cane zone in northeast Brazil.
AB  - A schedule of repeated chemotherapy with oxamniquine, consisting of biannual
      treatment of school-aged (7-13 years) children and annual treatment of all other
      age groups, was used in a representative rural village from a highly endemic area
      of schistosomiasis in Pernambuco. Significant reductions in infection were
      obtained only after two cycles of treatment, as the overall prevalence decreased
      from 72.6% to 41.7% and the geometric mean egg counts per gram of faeces among
      positives fell from 188.4 to 76. In a school-aged cohort (n = 29) three
      treatments at six-month intervals were necessary to significantly reduce the
      proportion of positives (from 75.9% to 51.7%). In a cohort of children under 7
      years of age (n = 20) the proportion of positives actually increased (from 30% to
      45%) despite two annual treatments. Water contact was intense and host snail
      density was relatively high. As there is no short-term perspective of improved
      sanitation, auxiliary measures such as focal mollusciciding are needed for an
      adequate control of schistosomiasis in this and alike areas.

PMID- 9921365
TI  - Urban schistosomiasis in Itamaraca Island, Pernambuco, Brazil: epidemiological
      factors involved in the recent endemic process.

PMID- 9921366
TI  - Activity of oxamniquine at skin, pulmonary and sexual maturation phases, on a
      Schistosoma mansoni strain (R1) previously reported as resistant at the adult
      phase.

PMID- 9921367
TI  - Evidence for functional ryanodine receptors in Schistosoma mansoni and their
      putative role in the control of calcium homeostasis.

PMID- 9921368
TI  - Protein deficiency impairs the schistosomicidal action of praziquantel.

PMID- 9921369
TI  - IgM antibodies to Schistosoma mansoni gut-associated antigens for the study of
      schistosomiasis transmission in Ribeirao Pires, Sao Paulo.
AB  - The potential of an immunofluorescence test for detection of IgM antibodies
      against Schistosoma mansoni gut-associated antigens (IgM-IFT) was evaluated as a
      tool for studying aspects related to the schistosomiasis transmission in Ribeirao
      Pires, in the metropolitan area of the capital of the State of Sao Paulo, Brazil.
      Children from a school with about 400 students, 6 to 18 years, were followed-up
      for two years. In the five surveys, carried out at 6-month intervals, from
      October 92 to October 94, serological (IgM-IFT) prevalence indices of 5.3%, 5.8%,
      6.2%, 2.9% and 3.3% were obtained. These indices were 7 to 10 times higher than
      the parasitological prevalence indices of 0.5%, 0.5%, 0.7%, 0.4% and 0%
      determined by the Kato-Katz method. Seroconversion from IFT negative to positive
      was indicating possible newly acquired S. mansoni infection in three children.
      But confirmation of infection by fecal examination was possible in only one
      child. The IgM-IFT can constitute a valuable tool for the improvement of the
      vigilance program in low endemic areas for schistosomiasis, better characterizing
      the S. mansoni transmission in such areas.

PMID- 9921370
TI  - A comparative study on IgG-ELISA, IgM-IFT and Kato-Katz methods for
      epidemiological purposes in a low endemic area for schistosomiasis.
AB  - The high sensitivity and the possibility of automation of the enzyme-linked
      immunosorbent-assay (ELISA) has indicated this technique as one of the most
      useful serological test for epidemiological studies. In the present study, an
      ELISA for detection of IgG antibodies against adult worm antigens (IgG-ELISA) was
      investigated for epidemiological purposes, in a rural area of the municipality of
      Itariri (Sao Paulo, Brazil). Blood on filter paper (1,180 samples) from about 650
      schoolchildren were submitted to ELISA and the data compared to the results of
      the parasitological method of Kato-Katz and also to the IgM-IFT
      (immunofluorescence test for IgM antibodies to gut associated antigens). The
      prevalence rates respectively of 8.5%, 43.0% and 56.2% by the Kato-Katz, IgG
      ELISA, and IgM-IFT methods suggest the poor sensitivity of the parasitological
      method for detection of Schistosoma mansoni eggs in individuals with low worm
      burden, situation commonly observed in low endemic areas. These results can
      partially explain the poor degree of agreement between the IgG-ELISA and the Kato
      Katz, as suggested by the Kappa index of 0.170. Otherwise, the Kappa index of
      0.675 showed substantial agreement between the two serological tests. Some
      discrepancy of results between the two serological techniques must be better
      investigated.

PMID- 9921371
TI  - Immunofluorescence test on Schistosoma mansoni worm paraffin sections (IgM-IFT)
      for the study of schistosomiasis transmission in Campinas, Sao Paulo, Brazil.
AB  - The detection of IgM antibodies for Schistosoma mansoni using gut-associated
      antigens (IgM-IFT) was compared to the parasitological Kato-Katz method for study
      of the transmission of schistosomiasis in an urban area in Campinas. About 400
      schoolchildren whose ages ranged from 6 to 18 years, were observed for a period
      of two years. Blood samples on filter paper and fecal samples were collected, at
      intervals of six months. Serological (IgM-IFT) prevalence rates of 1.2%, 4.3%,
      3.6%, 2.9% and 3.4% were obtained in five surveys carried out. S. mansoni eggs
      were detected in only one child out of the 225 children (0.4%) who were submitted
      to the Kato-Katz method (three slides for each fecal sample) in the 1st survey.
      Sixty eight children who submitted five blood samples, one for each survey, were
      found IFT negative throughout the study. No child was found to be IFT positive in
      all five surveys, and only four children showed IFT positive results in at least
      four surveys. Seroconversion from IFT negative to positive was observed from the
      1st to the 2nd survey in six children, from the 2nd to the 3rd survey in three
      children, from the 3rd to the 4th survey in four children, and from the 4th to
      the 5th survey in two cases. However, confirmation of S. mansoni infection using
      the fecal examination was not possible in any of the cases. Also, in most of them
      the IFT result oscillated from negative to positive and vice versa. Our data
      implied that recent transmission of schistosomiasis in the study area was not
      possible.

PMID- 9921372
TI  - Colon polyps in Schistosoma haematobium schistosomiasis.

PMID- 9921373
TI  - Potential spread of schistosomiasis in the periphery of greater metropolitan
      region of Rio de Janeiro.

PMID- 9921374
TI  - Susceptibility of Nectomys rattus (Pelzen, 1883) to experimental infection with
      Schistosoma mansoni (Sambon, 1907): a potential reservoir in Brazil.
AB  - The aim of the present research was to evaluate the potential of Nectomys rattus,
      the "water rat", to develop Schistosoma mansoni infection. Comparison with N.
      squamipes was carried out. Both species of rodents were submitted to
      transcutaneous infection using different infective cercariae loads: 50, 100 or
      500. N. rattus showed high susceptibility to S. mansoni, with an infection rate
      of 71%. Rodents were able to excrete viable eggs of S. mansoni in the faeces
      during all infection period. For both species, the small intestine, followed by
      the liver and the large intestine, presented the highest concentration of eggs
      among the surveyed organs. Infection caused no animal death. Moreover, N. rattus
      accomplished the parasite's life cycle, by infecting the snails Biomphalaria
      glabrata and later Mus musculus. These evidences indicate that both N. rattus, as
      for N. squamipes are potential reservoirs for schistosomiasis in Brazil.
      Considering the fact that N. rattus and N. squamipes exist in the same natural
      ecosystems of S. mansoni, we suggest that these rodents must be regarded as
      influential factors in epidemiology surveys.

PMID- 9921375
TI  - Effect of Biomphalaria straminea plasma in the phagocytosis of Biomphalaria
      glabrata hemolymph cells.

PMID- 9921376
TI  - Morphological study of adult male worms of Schistosoma mansoni Sambon, 1907 by
      confocal laser scanning microscopy.
AB  - Aiming to detail data obtained through brightfield microscopy (BM) on
      reproductive, excretory and digestive system, specimens of Schistosoma mansoni
      eight weeks old, were recovered from SW mice, stained with Langeron's carmine and
      analyzed under a confocal laser scanning microscope CLSM 410 (Carl Zeiss). The
      reproductive system presented a single and lobate testis, with
      intercommunications between the lobes without efferent duct. Supernumerary
      testicular lobe was amorphous and isolated from the normal ones. Collecting
      tubules (excretory ducts), followed by the excretory bladder, opening to the
      external media through the excretory pore, were observed at the posterior
      extremity of the body. In the digestive tract, a cecal swelling was noted at the
      junction that originates the single cecum. It was concluded that through confocal
      laser scanning microscopy, new interpretations of morphological structures of S.
      mansoni worms could be achieved, modifying adopted and current descriptions. The
      gonad consists of a single lobed testis, similar to that observed in some
      trematode species. Moreover, the same specimens can be observed either by BM or
      CLSM, considering that the latter causes only focal and limited damage in tissue
      structures.

PMID- 9921378
TI  - The situation of hepatosplenic schistosomiasis in Brazil today.
AB  - Specific chemotherapy against schistosomiasis together with environmental changes
      occurring in endemic areas of Brazil are causing a revolution in the clinico
      pathological presentation of the disease when comparing to date from 10 to 15
      years ago. To update the subject, an inquiry was made among the most experienced
      Brazilian investigators in this field. They agree that a decrease of about 50 to
      70% in prevalence, and an even higher decrease in incidence are taking place in
      Brazil today. The prevalence of schistosome-infection has decreased in some areas
      and increased in other, with spreading sometimes occurring to peri-urban regions,
      indicating that schistosomiasis control depends on the application of multiple
      measures. General clinical and pathological manifestations related to
      hepatosplenic disease, such as ascites, gastric hemorrhages, big-spleen syndrome,
      cor pulmonale, glomerulopathy, etc. are also less severe nowadays than they used
      to be in the past.

PMID- 9921377
TI  - Schistosoma mansoni Sambon, 1907: morphometric differences between adult worms
      from sympatric rodent and human isolates.
AB  - A computer software for image analysis (IMAGE PRO PLUS, MEDIA CYBERNETICS) was
      utilized in male and females adult worms, aiming the morphological
      characterization of Schistosoma mansoni samples isolated from a slyvatic rodent,
      Nectomys squamipes, and humans in Sumidouro, Rio de Janeiro, Brazil and recovered
      from Mus musculus C3H/He. The following characters for males's testicular lobes
      were analyzed: number, area, density, larger and smaller diameter, longer and
      shorter axis and perimeter and extension; for females: area, longer and shorter
      axis, larger and smaller diameter and perimeter of the eggs and spine; oral and
      ventral suckers area and distance between them in both sex were determined. By
      the analysis of variance (one way ANOVA) significant differences (p < 0.05) were
      observed in all studied characters, except for the density of testicular lobes.
      Significant differences (p < 0.05) were detected for all characters in the female
      worms. Data ratify that sympatric isolates present phenotypic differences and the
      adult female characters are useful for the proper identification of S. mansoni
      isolates.

PMID- 9921379
TI  - Systematic reviews of strategies to prevent motor vehicle injuries.
AB  - BACKGROUND: Information on which strategies have been shown to be effective,
      which are ineffective, and which strategies have been inadequately evaluated is
      important for both public policy and future research. OBJECTIVE: To provide
      systematic reviews of the literature on important strategies to prevent motor
      vehicle injuries. METHODS: The Injury Control Research Centers (ICRCs) funded by
      the Centers for Disease Control and Prevention identified 9 important motor
      vehicle injury prevention strategies. A systematic review of the literature in 9
      different computerized databases was conducted to identify relevant controlled
      trials. These were critically reviewed and summarized. RESULTS: A total of 54,078
      citations were reviewed; 1,111 met initial screening criteria. The reports for
      these citations were obtained and critically reviewed by the ICRCs. Standard
      criteria for inclusion of articles in the review and for evaluating the
      methodological quality of the articles were applied. Few randomized controlled
      trials were found; most controlled studies were either comparisons over time
      and/or across different populations. Nevertheless, these studies were able to be
      summarized to provide meaningful conclusions about the effectiveness of various
      interventions to decrease morbidity and mortality from motor vehicle crashes.
      CONCLUSIONS: A large body of literature on motor vehicle injury interventions
      exists. The summary of this literature will provide useful information to direct
      policy and future research efforts.

PMID- 9921380
TI  - Comment on occupant and licensing interventions.

PMID- 9921381
TI  - Importance of systematic reviews and meta-analyses for research and practice.

PMID- 9921382
TI  - Effectiveness of health promotion programs to increase motor vehicle occupant
      restraint use among young children.
AB  - OBJECTIVE: To review the effectiveness of nonlegislative community and clinical
      programs to increase the rate of child motor vehicle occupant restraint use among
      children under the age of 5 years. METHOD: This was a systematic review of the
      world's published literature. The Cochrane Collaboration protocol was used to
      conduct the literature search. The following databases were searched for
      literature on this topic: MEDLINE, EMBASE, NTIS, PsychINFO, ERIC, Nursing and
      Allied Health, Transportation Research and Information Service, and EI Compendex.
      The bibliographies of relevant publications were used to search for additional
      references. SELECTION CRITERIA: Studies were included if they evaluated a
      clinical or community-based intervention designed to increase the use child
      restraint devices among motor vehicle passengers under the age of 5 years.
      Studies of the effects of legislation or law enforcement programs were excluded.
      All study design types, including randomized controlled trials, controlled
      trials, and controlled or uncontrolled pre/post evaluations, were included.
      Studies were excluded if there was either no control group or no baseline data
      with which to compare outcome data. Studies were also excluded if they did not
      use observed restraint use as at least one of the outcome measures. DATA
      COLLECTION: Each study was reviewed in depth with special attention to the
      strength of study design. Outcomes were assessed in terms of the absolute
      difference in observed restraint use within and/or between groups across study
      intervals. RESULTS: A total of 18 studies met inclusion criteria for in-depth
      review. Pooling of results was not possible because of the large differences
      between studies with regard to study design, settings, target groups,
      intervention methods, and units of analysis. There were a total of three
      randomized controlled trials, four controlled trials without random individual or
      group assignment, three controlled pre-post evaluations, and eight uncontrolled
      pre/post studies. Among preschool programs, short-term absolute percentage point
      gains in seat belt use rates ranged from 12% to 52% but only from 8% to 14% one
      month or more after the intervention. Among community-based media campaigns, long
      term child restraint use increased by an absolute margin of 5% to 14%. Of the
      eleven peri-partum counseling programs, long-term follow-up revealed gains of 6%
      to 27% with most between 10% to 15%. Many studies had serious design flaws that
      could overestimate the magnitude of the effect. CONCLUSIONS: Programs to increase
      the rate of child restraint use among child occupants of motor vehicles appear to
      have overall moderate short-term effectiveness. The magnitude of the positive
      program effects one or more months after the intervention appear to diminish
      substantially. There is a strong need for high quality randomized controlled
      trials to determine the long-term effectiveness of child restraint promotion
      programs.

PMID- 9921383
TI  - Evaluating interventions that promote the use of rear seats for children.
AB  - OBJECTIVE: To evaluate interventions that promote the use of the rear seat among
      children riding in motor vehicles. SEARCH STRATEGIES: Using the Cochrane
      Collaboration search strategy, we searched in electronic databases and reference
      lists of past reviews and review articles. We also searched among studies from
      government and research agencies in the United States and abroad, and contacted
      experts in the field. SELECTION CRITERIA: Studies for selection had to be
      evaluations of interventions in defined populations, with a clear description of
      the program and the outcomes evaluated. Outcomes had to be measured in an
      objective manner, and there needed to be a comparison group. DATA COLLECTION AND
      ANALYSIS: Six studies met the selection criteria. Changes in the proportion of
      observed children traveling in the rear seats before and after the implementation
      of the intervention were the main outcome of interest. MAIN RESULTS: Two studies
      evaluating the effectiveness of educational campaigns promoting the use of the
      rear seat found increases in the proportion of children riding in the rear seats,
      but only in one study were the increases statistically significant (from 86% to
      91%). The four remaining studies reported changes in seating location as a side
      effect of legislation requiring child restraint use among children traveling in
      the front seats. In two of these four studies, the percentage of children riding
      in the rear seats significantly increased from 49% to 62% and from 88% to 98%. In
      the remaining two studies there were small, but not statistically significant,
      changes in the proportion of children riding in the rear seats, with percentages
      remaining around 60% and 85%. CONCLUSIONS: Interventions aimed at promoting the
      use of rear seats by children traveling in motor vehicles have been rare. Only
      one educational program whose only objective was to promote rear seating location
      was found and this 1973 Danish study had a positive impact. The other educational
      campaign, a pilot program that also focused on improving child restraint use, had
      no significant impact in promoting seating of children in the rear. We did not
      find any evaluation of legislation prohibiting children to sit in the front
      seats. Legislation requiring proper child restraint use in the front seats (and
      thus, compelling unrestrained children to seat in the rear) has produced, for the
      most part, a nonsignificant increase in the proportions of children sitting in
      the rear.

PMID- 9921384
TI  - Effectiveness of primary and secondary enforced seat belt laws.
AB  - OBJECTIVE: The objective of this study was to determine the relative efficacy of
      primary and secondary enforced motor vehicle occupant restraint laws on the
      outcomes of restraint use, crash-related mortality, and crash-related injuries.
      SEARCH STRATEGY: We used the Cochrane Collaboration search strategy to search the
      following electronic databases: MEDLINE, EMBASE, National Technical Information
      Service (NTIS), Psyc-INFO, ERIC, Nursing and Allied Health (CINAHL),
      Transportation Research Information Service (TRIS), and EI Compendex. The
      reference lists from each potentially eligible study were checked, and
      knowledgeable people in the field were contacted, for additional leads to
      published reports. SELECTION CRITERIA: Studies had to include a comparison of
      primary enforcement law to no law, secondary enforcement law to no law, or a
      primary to a secondary law. Any study design was acceptable. Acceptable outcome
      measures included observed restraint use, and counts or rates of deaths or
      serious injuries. DATA COLLECTION: Data were collected using a standard abstract
      reporting from. Relative differences in outcomes and absolute differences were
      calculated when possible. MAIN RESULTS: We identified 48 studies for the review.
      When places or time periods with primary enforcement laws were compared to those
      without such laws, the relative prevalence of seat belt use ranged from 1.5 to
      4.5; the prevalence differences ranged from 10 to 50 per 100 observed drivers.
      Secondary laws had smaller effects. Two studies evaluated a change in law from
      secondary to primary enforcement; this was associated with an increase in belt
      use 6 months later of 5.3 per 100 observed drivers in Louisiana and 18 per 100
      drivers in California. Primary enforcement laws were associated with a relative
      risk of death in MV crashes of .54 to .97. The reduction in mortality associated
      with secondary enforcement laws was much more modest, with relative risks
      estimates of .81 to 1.025. Primary enforcement laws were associated with a
      relative risk of severe injuries of .20 to .89; the association of secondary
      enforcement laws with severe injuries was smaller. CONCLUSIONS: Our review of
      existing studies suggests that primary enforcement laws are likely to be more
      effective than secondary laws. However, few studies are of good quality, and
      quantitative estimates of the relative effect of primary compared with secondary
      laws are limited.

PMID- 9921385
TI  - Effects of high school driver education on motor vehicle crashes, violations, and
      licensure.
AB  - OBJECTIVE: We sought evidence in the research literature to determine if (1) high
      school-aged persons who enroll in a driver education course have fewer motor
      vehicle-related crashes or violations, or are more likely to obtain a drivers
      license, than those who do not enroll in driver education courses, and (2) the
      availability of high school driver education courses is associated with lower
      community rates of motor vehicle crashes among young drivers. METHODS: To be
      included, a study must: (1) assess the effects of driver education courses or
      legislation for high school-aged persons; (2) present non-self-reported data for
      at least one of the following outcome measures: driver licensure rates, motor
      vehicle-related violations, or crashes; (3) include some form of no intervention
      comparison group; (4) adequately control for potentially confounding variables;
      (5) randomly assign participants to control or treatment groups, if a controlled
      trial. RESULTS: Nine studies met our inclusion criteria. Based on these studies,
      there is no convincing evidence that high school driver education reduces motor
      vehicle crash involvement rates for young drivers, either at the individual or
      community level. In fact, by providing an opportunity for early licensure, there
      is evidence that these courses are associated with higher crash involvement rates
      for young drivers. CONCLUSIONS: Although few driver education curricula have been
      carefully evaluated, in the absence of evidence that driver education reduces
      crash involvement rates for young persons, schools and communities should
      consider other ways to reduce motor vehicle-related deaths in this population,
      such as graduated licensing.

PMID- 9921386
TI  - Effectiveness of graduated driver licensing in reducing motor vehicle crashes.
AB  - OBJECTIVE: To determine whether graduated driver licensing (GDL) systems and
      nighttime curfews reduce motor vehicle crashes, fatalities, or injuries among
      young drivers. METHODS: We used Cochrane Collaboration search strategies to
      locate studies of graduated licensing or night driving restrictions. Studies were
      selected if they examined the effects of either (1) a comprehensive graduated
      driver licensing system including well-integrated components, or (2) nighttime
      driving restrictions/curfews that could affect young persons' nighttime driving,
      on a clearly defined crash or injury outcome. Seven studies met inclusion
      criteria. RESULTS: Two independent studies of the New Zealand graduated licensing
      program found a sustained 7%-8% reduction in teen driver crash injuries
      attributable to the program. No other full graduated licensing system has been
      evaluated to date. Four studies of either a general curfew or a nighttime driving
      restriction for teens, a key element of graduated licensing, found substantial
      crash reductions during restricted hours, with 23%-25% lower crash injury and
      fatality rates for curfews beginning prior to midnight. One study found no change
      in late night crashes before and after a 1 a.m.-6 a.m. night driving restriction
      took effect. CONCLUSIONS: The logic and empirical bases for graduated licensing
      are sound. Moreover, there is evidence that one central element, a restriction on
      nighttime driving by novices, reduces young driver crashes. However, a definitive
      conclusion about the effectiveness of GDL systems for reducing motor vehicle
      crashes or crash-related injuries must await examination of other GDL systems.
      This should be possible within the next few years, as several states and Canadian
      provinces have recently enacted GDL programs.

PMID- 9921387
TI  - The effect of random alcohol screening in reducing motor vehicle crash injuries.
AB  - OBJECTIVE: Programs that randomly stop drivers to detect alcohol use have been
      introduced as a deterrence measure for drinking and driving. The objective of
      this review is to determine if this random screening reduces fatalities and
      injuries. The two types of random screening programs included are Random Breath
      Testing and Sobriety Checkpoints. METHODS: Fourteen studies met inclusion
      criteria, which required an evaluation of a random screening program with a
      control population or baseline comparison. Proportional decreases in total or
      alcohol-related fatalities or injuries were the outcome of interest. MAIN
      RESULTS: All fourteen studies found that random screening was effective in
      reducing fatalities and injuries. The decreases found had wide variation, but did
      not depend on the size of the population. Alcohol-related fatalities generally
      showed the greatest decreases, ranging from 8% to 71%. The few multivariate
      analyses showed that random screening significantly reduced crashes and injuries.
      CONCLUSIONS: Random screening appears to be effective in a wide range of both
      United States and Australian populations. Although there are many limitations to
      the studies reviewed, such as the difficulty in determining alcohol involvement
      and the inability to control for the presence of other drunk driving reduction
      programs, the weight of the evidence indicates that random screening reduces
      fatalities and injuries. There was some disagreement among studies as to how long
      the effects of random alcohol screening can be sustained and the level of
      enforcement necessary, and these remain questions to be answered.

PMID- 9921388
TI  - The specific deterrence of administrative per se laws in reducing drunk driving
      recidivism.
AB  - OBJECTIVE: To determine if administrative per se laws are more effective than
      other forms of sanction against drunk drivers. SEARCH STRATEGIES: The overall
      goal of the search strategy was to identify all relevant research concerning the
      specific effects of administrative per se laws in reducing drunk driving
      recidivism, traffic crashes, and other alcohol-related driving offenses by those
      drivers with suspended licenses. Known review articles and MEDLINE reviews formed
      the reference bibliography; numerous databases were searched from 1966 to the
      present, using such terms as alcohol, driver's license, recidivism, deterrence,
      and legislation. SELECTION CRITERIA: To be selected the study had to be designed
      to test the presence of an administrative per se license revocation or
      restriction in a defined cohort, have a suitable comparison cohort whose
      sanctions for drunk driving were not administrative per se, and provide relevant
      data that lead to an objective assessment of recidivism. Types of studies
      included were randomized controlled trials, nonrandomized controlled trials,
      other specialized cohort studies, and case-control studies. Three studies were
      identified; all met inclusion criteria. DATA COLLECTION AND ANALYSIS: One of the
      studies provided Kaplan-Meier survival curves for failure times defined as days
      to new conviction following the initial arrest. Odds ratios and 99% confidence
      intervals were extracted from two of the studies and additional information was
      supplied by the author of one of the studies. MAIN RESULTS: One study found that
      one state in the United States experienced a reduction of about one third in
      repeat arrests for drunk driving over a 3-year period among those who were
      arrested under administrative per se, relative to recidivism seen in a comparison
      cohort of drivers prior to administrative per se. Two other states did not
      experience any change in recidivism. The second study found that drivers whose
      licenses were suspended under administrative per se were 39% less likely during
      the first year following suspension to be rearrested on the charge of driving
      while intoxicated compared with a comparison cohort. This differential persisted
      into the second year of follow-up, but disappeared by the third year. The third
      study found both first offenders and repeat offenders arrested under
      administrative per se were 34% less likely to be involved during the year
      following their arrest in a subsequent motor vehicle crash compared with those in
      the comparison cohort. Drivers with administrative per se suspensions were 21%
      less likely to be involved in additional drunk driving offenses, and 27% less
      likely to be involved in reckless driving offenses related to alcohol.
      CONCLUSIONS: Administrative per se laws governing license restriction for drivers
      have been shown to be effective in some states but not others in decreasing the
      rates at which these same drivers are subsequently involved in a motor vehicle
      crash or in another alcohol-related offense, compared with drivers who were
      sanctioned through other conventional judicial processes. Replications are needed
      in other states or large driver populations using improved methodology.

PMID- 9921389
TI  - Evaluation of the effectiveness of low blood alcohol concentration laws for
      younger drivers.
AB  - OBJECTIVE: This study aimed to determine whether low blood alcohol concentration
      (BAC) laws among younger drivers reduce motor vehicle injuries. SEARCH
      STRATEGIES: We used Cochrane Collaboration search strategies of electronic
      databases, reference lists of past studies and reviews, governmental agency
      publications, and direct contacts with experts in the field. SELECTION CRITERIA:
      Studies were included if they provided objectively measured data on an injury
      outcome and if they used an appropriate comparison group to assess the impact of
      the law. DATA COLLECTION AND ANALYSIS: Six studies met selection criteria. We
      abstracted information using standard data collection sheets. Since the studies
      all were of ecologic designs, we did not carry out any pooled analyses. MAIN
      RESULTS: All six studies showed a reduction in injuries or crashes after the
      implementation of the law, although, for three studies, these reductions were not
      statistically significant. This study with the smallest reduction in injuries was
      also the study with the least power. This study only had a power of 70% to detect
      a hypothetical 10% decline in serious injuries. Reductions in outcome in the
      other studies ranged from 11% to 33% with a cluster of parameter estimates just
      under 20%. One study evaluated laws with differing levels of BAC and found a dose
      response effect. The greatest reduction (22%) was reported for nighttime, single
      vehicle fatalities in those states with zero BAC laws. In states with 0.02% BAC
      laws, the reduction averaged 17% and in states with 0.04 to 0.06% BAC laws, the
      reduction was only 7%. CONCLUSIONS: Despite the methodologic difficulties of
      ecologic studies, the six studies reviewed represent accumulating evidence in
      support of the effectiveness of these laws. The sum of the evidence is
      strengthened because similar results were found in different countries (Australia
      and the United States), using different laws (some aimed at younger drivers and
      others aimed at inexperienced drivers), using different outcome variables
      (fatalities, injuries, and crashes), and using different research methodologies
      (interrupted time series and pre- and post-studies). In addition, the largest
      U.S. study found that laws with lower BAC limits resulted in greater casualty
      reductions, analogous to a dose response effect.

PMID- 9921390
TI  - Effectiveness of ignition interlock devices in reducing drunk driving recidivism.
AB  - OBJECTIVE: To determine if ignition interlock devices reduce driving while
      intoxicated (DWI) recidivism. SEARCH STRATEGIES: Cochrane Collaboration search
      strategies were used. SELECTION CRITERIA: Studies for selection examined the
      effectiveness of interlock programs in a defined population. Studies were
      required to have a clear description of the program and outcomes evaluated, to
      have a comparison group and to provide interpretable data. DATA COLLECTION AND
      ANALYSIS: A total of 31 studies were found. Ten studies met the selection
      criteria. Three of these studies were eliminated from further analysis because
      they did not contain original data. A fourth study was eliminated due to
      methodologic weaknesses, leaving six studies for final review and analysis.
      Pooled analyses were not done because studies did not follow similar methods over
      comparable time periods. MAIN RESULTS: Five of the six studies found interlocks
      were effective in reducing DWI recidivism while the interlock was installed in
      the car. In the five studies demonstrating a significant effect, participants in
      the interlock programs were 15%-69% less likely than controls to be re-arrested
      for DWI. The only reported randomized, controlled trial demonstrated a 65%
      reduction in re-arrests for DWI in the interlock group, compared with the control
      group. CONCLUSIONS: Alcohol ignition interlock programs appear to be effective in
      reducing DWI recidivism during the time period when the interlock is installed in
      the car. Future studies should attempt to control for exposure (i.e., number of
      miles driven) and determine if certain sub-groups are most benefited by interlock
      programs.

PMID- 9921391
TI  - Vasculitis and chronic persistent viral infections.

PMID- 9921392
TI  - Human immunodeficiency virus-related vasculitis. Clinical presentation of and
      therapeutic approach to eight cases.
AB  - Vasculitides occurring during the course of human immunodeficiency virus (HIV)
      infection are heterogeneous in their clinical presentation, time of occurrence,
      histological findings and etiological factors. Some of them can be directly
      attributed to HIV infection and their treatment might require new therapeutic
      approaches, such as plasma exchanges, specific antiviral agents and/or
      vasodilators. We report 8 cases of vasculitis associated with HIV. Five of them
      met the classification criteria of polyarteritis nodosa and had symptoms
      compatible with microscopic polyangiitis. Etiological agents were not identified.
      Although hepatitis B virus, hepatitis C virus (HCV) and other viruses or
      opportunistic agents were detected in some patients, HCV was suspected of being
      the etiological factor in only 1 of them. Focusing on viral and immunological
      features, the possible mechanisms of vasculitis development in HIV+ patients are
      discussed. Long-term follow-up indicates a clear benefit of regimens including
      antiviral agents, vasodilators and plasma exchanges. No deterioration of AIDS
      status was observed with this treatment and no relapse was recorded.

PMID- 9921393
TI  - [Fibromyalgia. A critical review].
AB  - Fibromyalgia is a chronic pain syndrome, more common in women. Its prevalence is
      estimated around 2% in the general population, and up to 20% among rheumatology
      outpatients. Besides musculoskeletal pain, symptoms as fatigue and sleep
      disturbance are considered characteristic. Research criteria have been set up,
      but their seemingly preciseness is unable to distinguish clearly between
      fibromyalgia and other functional somatic syndromes (chronic fatigue syndrome,
      irritable bowel syndrome) and psychiatric disorders (depression, anxiety), with
      which a striking comorbidity is documented. The diagnosis of fibromyalgia does
      not theoretically require the exclusion of muscle, joint, or metabolic diseases,
      but in clinical practice this problem proves to be of crucial importance. There
      are numbers of pathophysiological hypothesis for fibromyalgia, but none of them
      is fully satisfying: muscle is probably innocent; sleep disturbance, although
      sometimes considered a landmark of the syndrome, is unspecific; stress response
      studies show subtle anomaly; psychiatric disorders may represent factors of
      vulnerability and perpetuation rather than causes. We propose to include some of
      these etiological contributors in vicious circles leading to a "final common
      pathway" characterized by generalized hyperalgesia. Treatments of fibromyalgia,
      whether pharmacological (antidepressants) or psychological (cognitive-behavioral
      therapies) are of little efficacy, and the global prognosis of fibromyalgia is
      poor. However, the outcome might prove better outside the specialized clinics in
      which studies of chronic sufferers with severe abnormal illness behaviors are
      done. The social consequences of the popularization of the diagnosis of
      fibromyalgia should not be neglected.

PMID- 9921394
TI  - [Pathology of giant cell arteritis].
AB  - Two inflammatory vascular diseases often show multinucleated macrophages:
      Takayasu's disease and Horton's disease. Takayasu's disease is a segmentary
      panarteritis most prominent in the adventitia. Lesions show an inflammatory
      infiltrate close to the external elastic lamina. Progressive stenosis of the
      artery, sometimes complicated by calcifying atheroma is the typical course.
      Horton's disease or temporal arteritis is another segmentary arteritis. Lesions
      show a mixed inflammatory infiltrate partly localized in the adventitia where
      there are T CD4+ lymphocytes secreting II-2 and IFN-gamma and also macrophages
      expressing TGF beta 1, IL-6 and IL-1 beta, and partly situated in the interior
      part of the wall, around the internal elastic lamina, and mostly made of
      macrophages and giant cells which produce TNF, collagenase and nitric oxide that
      are responsible for destruction of the wall. The variety and subtleness of some
      lesions do not always make a precise diagnosis possible. But any inflammatory
      vascular lesion, even slight, can reveal a systemic vasculitis.

PMID- 9921395
TI  - Giant cell arteritis--a molecular approach to the multiple facets of the
      syndrome.
AB  - Molecular studies of giant cell arteritis indicate that T cells are recruited to
      the wall of medium-sized and large arteries, are activated locally, produce IL-2
      and IFN-gamma, and regulate the activity of tissue-infiltrating macrophages.
      Downstream effects of T cell activation include the production of proinflammatory
      cytokines, metalloproteinases, and growth factors. Growth factors are
      instrumental in the process of intimal hyperplasia, leading to luminal occlusion
      and tissue ischemia. The amounts of IL-2, IFN-gamma, and the growth factor PDGF
      in the vascular lesions varies among patients and are correlated with differences
      in patterns of clinical manifestations. Giant cell arteritis complicated by
      cranial ischemia, such as anterior optic neuropathy or stroke, is characterized
      by high levels of IFN-gamma and PDGF. If the IFN-gamma-PDGF loop is less
      developed, fever and wasting can dominate the disease. Dominant production of IL
      2 is associated with polymyalgia rheumatica. The finding of different
      inflammatory pathways translating into different clinical phenotypes may reflect
      differences in the contribution of the arterial wall. Alternative hypotheses
      include a role of multiple disease-inducing antigens with different tissue
      distributions or tropisms.

PMID- 9921396
TI  - [Epidemiology and etiological factors in giant cell arteritis (Horton's disease
      and Takayasu's disease)].
AB  - Temporal arteritis is without a doubt the most frequent vasculitis. Incidence is
      age related and most patients are over 50. The incidence in Caucasian populations
      shows a North-South gradient with a clear predominance in northern Europe and in
      the northern part of the United States. In these populations, annual incidence is
      estimated at 15 to 30/100,000 persons over 50 years of age. The sex ratio (F/M)
      ranges from 2 to 4. Data in France, Scotland, Italy and Israel show an annual
      incidence below 10/100,000 inhabitants. The disease is very uncommon in persons
      of African or Asian ethnic origin. Histology and immunohistochemistry studies of
      the temporal artery walls favor a vasculitis triggered by one or more unknown
      antigens, but the cause of temporal arteritis remains unknown. A link with HLA
      DR4 was demonstrated early. The epidemiology of Takayasu's disease is less well
      known except for the very strong female predominance (90% of cases). The disease
      is frequent in Japan, Asia, India and South America, more uncommon in Europe and
      North America. The "gradient" is thus inverted compared with temporal arteritis.
      In Japan, among 300,000 autopsies, only 0.03% cases of Takayasu disease have been
      observed. The incidence of the disease in one study was 2.6 cases per million
      inhabitants per year. Unlike temporal arteritis, most cases begin early in the 10
      to 30 year age range. Genetic susceptibility linked to HLA BW52 is observed in
      Asia while in the United States, it would appear, though on small numbers of
      cases, that the frequencies of MB3 and DR4 are increased. We emphasize the
      epidemiological relationship with tuberculosis and Takayasu disease.

PMID- 9921397
TI  - [Horton's disease, polymyalgia rheumatica, and cardiovascular risk factors. A
      case-control, prospective multicenter study].
AB  - OBJECTIVES: To assess the potential pathogenetic role of cardiovascular risk
      factors measured at diagnosis in temporal arteritis. METHODS: Four hundred newly
      diagnosed patients and their age- and sex-matched controls randomly selected from
      the general population were included in a prospective multicentric cas-control
      study. RESULTS: In female patients, smoking increased the disease risk by a
      factor of 6 (95% CI: 2-17, p = 0.00006), and by a factor of 17 in case of > 10
      pack-years. Pre-existing peripheral arterial disease increased the risk by a 4.5
      fold factor (95% CI: 2-11, p = 0.0003), both in patients with a positive and
      those with a negative biopsy. Smoking alone appeared as a risk factor for
      polymyalgia rheumatica (OR: 3,64, 95% CI: 1.07-12.40). In male patients, none of
      the cardiovascular risk factors studied was positivity associated with the
      disease. CONCLUSION: Smoking and a pre-existing peripheral arterial disease are
      independently associated with temporal arteritis in women. Risk factors for
      disease with an imbalanced sex ratio should be studied separately for each sex in
      matched case-control studies in order to avoid matching bias.

PMID- 9921398
TI  - [Immunosuppressive agents in Horton's disease. Which drug for which indication?].
AB  - Corticosteroids remain the cornerstone treatment of giant cell arteritis. Steroid
      related toxicity and needs for alternative therapeutic regimens in patients
      experiencing recurrent active or steroid-resistant diseases, are the main reasons
      for searching a steroid-sparing agent. Regarding disease pathogenesis,
      immunosuppressive agents might be useful drugs. Methotrexate is the most widely
      studied agent in this indication. However, available data are incomplete and
      studies have included only polymyalgia rheumatica or both polymyalgia rheumatica
      and giant cell arteritis affected patients. Results of these studies evoke the
      possibility of using methotrexate in steroid-dependent or resistant diseases, as
      well as a steroid-sparing agent in order to taper off and stop steroids quickly;
      with an acceptable toxicity. Azathioprine may be used to control steroid
      dependant or resistant diseases, but toxicity appears to be higher. An open
      prospective study compared azathioprine and methotrexate and concluded to the
      superiority of methotrexate. Available data concerning cyclophosphamide and
      cyclosporine A are too incomplete. A satisfactory steroid-sparing agent in giant
      cell arteritis is still unknown. Currently, methotrexate, and probably
      azathioprine, appear to be the most useful agents in this indication. However,
      there is no demonstration that using an immunosuppressive agent in giant cell
      arteritis could reduce steroid-related morbidity.

PMID- 9921399
TI  - [Principles of acute treatment of Horton's disease. Role of high-dose
      corticosteroid therapy].
AB  - Corticosteroid therapy, the elective treatment for temporal arteritis, can
      produce adverse effects on bone in this elderly population which usually occur
      late after acute high-dose administration. Such adverse effects are exceptional
      and generally have little impact as long as certain cortisone-sparing principles
      are followed: duration of acute treatments should be as short as possible; dosage
      can be tapered off rapidly, cutting the acute dose in half in 4 weeks; to titrate
      dosage, inflammatory proteins should be monitored (especially CRP because of its
      rapid kinetics and sometimes another protein with slower kinetics); this appears
      to be more useful for cortisone-sparing than the classical method based on
      clinical analysis and sedimentation rate; acute regimens should be accompanied by
      anticoagulation until figrinogen has returned to normal levels; clinical relapses
      during treatment are usually benign and can generally be controlled by raising
      the dose slightly; in case of failure due to an acute flare-up far from
      corticosteroid administration, it would be interesting to study the cortisone
      sparing effect of giving a 240 mg i.v. bolus of methylprednisolone followed by
      low-dose corticosteroids; if the relapse is only expressed in laboratory tests,
      holding the dose at same plateau for two weeks generally leads to spontaneous
      normalization. Intravenous bolus methlyprednisolone is well tolerated in this
      population of elderly patients. There is no recognized indication in the
      uncomplicated forms of temporal arteritis. The cortisone-sparing effect of this
      technique may result from the fact that the acute oral dose can be reduced.
      Complicated forms, particularly with ocular involvement, are recognized
      indications for bolus administration although the administration modalities have
      not yet been validated. In patients with overt ocular involvement, repeating
      emergency high-dose i.v. boluses every 6 to 8 hours warrants evaluation with the
      objective of recovering visual function.

PMID- 9921400
TI  - [Borrelia burgdorferi, taxonomy, pathogenicity and spread].
AB  - Borrelia burgdorferi sensu lato is a bacterial complex of at least 10 species,
      most of which are non pathogenic for humans. Non pathogenic species seem to be
      more vector-specific, their distribution being restricted to that of this vector.
      In opposition, the three species pathogenic for humans, Borrelia burgdorferi
      sensu stricto (B.b.s.s.), Borrelia garinii (B.g.), and Borrelia afzelii (B.a.),
      are transmitted by several species of ticks more diversified in their host
      choice. Each of these three species is associated with a preferential
      organotropism: articulation for B.b. s.s., neurologic system for B.g. and skin
      for B.a. Strains belonging to these three species are much more frequently
      isolated from vectors and have a much larger area of expansion than the non
      pathogenic species. Indeed, their geographical distribution corresponding to that
      of their vector comprises one or two continents. B.g. and B.a., transmitted by
      Ixodes ricinus and Ixodes persulcatus, are spread throughout Eurasia. B.b. s.s.
      is the only species spread on two continents separated by an Ocean: North America
      (vectors: I. scapularis and I. pacificus) and Europe (I. ricinus). Combining of
      epidemiological data and molecular analyses shows that B.b. s.s. probably
      originated in America and later on, very recently (after 1492), migrated to the
      European continent.

PMID- 9921401
TI  - [Corticosteroid-induced epidural lipomatosis. Efficacy of medical treatment].
AB  - We describe a further case of cauda equina compression secondary to steroid
      induced epidural lipomatosis in a patient treated for IBD. The diagnosis was
      rapidly confirmed by MRI allowing conservative management by corticosteroid
      withdrawal as well as use of hygiene and dietary measures. Therapeutic efficacy
      was noted on a clinical basis and confirmed by repeated follow-up MRI exams which
      showed regression of fat accumulation. Symptomatic epidural lipomatosis is
      probably underestimated because physicians concerned by steroid treatment are not
      fully informed about this potentially severe and usually iatrogenic disease.
      Also, proper medical attention to the first neurological symptom in these
      patients might help limit therapeutic management to a medical measurer, before
      requiring surgical decompressive surgery.

PMID- 9921402
TI  - Pericardial tamponade as the first manifestation of dermatopolymyositis.
AB  - Pericardial involvement in polymyositis and dermatomyositis (PM/DM) is rare,
      usually asymptomatic and exceptionally part of the initial presentation. We
      describe a 37-year-old patient hospitalized for overt acute pericarditis,
      revealing dermatomyositis, which to our knowledge has not been previously
      reported. Pericardial puncture relieved the patient. The pericardial fluid was
      citrine yellow, exsudative, and mainly contained lymphocytes. Search for LE cells
      and anti-DNA antibodies was negative, whereas the antinuclear antibodies and the
      rheumatoid factor were present in the pericardial fluid. A biopsy of the
      pericardium showed a non-specific chronic inflammatory state and the search for
      an etiology was negative. There was no sign of tuberculosis, systemic lupus, nor
      neoplasia. Moreover bacteriological cultures and HIV serology were negative.
      After pericardiostomy associated with corticosteroid therapy at the dose of 1
      mg/kg/day, outcome was good with a resolution of the pericarditis confirmed at
      one-year follow-up. Since pericardial tamponade, even though rare, may be fatal
      in a patient with dermatomyositis, we emphasize that a two dimensional
      echocardiographic study should be performed in all patient presenting with
      dermatopolymyositis.

PMID- 9921403
TI  - [Case report of an "iron eater"].

PMID- 9921404
TI  - Lack of significant alteration of histamine-induced response in aorta from
      diabetic rats induced by streptozocin.
AB  - Effect of histamine on aortic contraction between age-matched control and
      diabetic rats induced by streptozocin were compared in vitro. It was shown that
      the aortic response to histamine in 12-week diabetic rats remained unchanged,
      even though the methoxamine-induced contraction was potentiated significantly in
      diabetic aorta. The significant potentiation of the methoxamine-induced aortic
      contraction implies that the diabetes-induced change in aortic response to drugs
      has occurred in 12-week diabetic aorta. Since histamine is an endothelium
      dependent vasoactive agent, the lack of change of the histamine-induced response
      in 12-week diabetic aorta suggests that the histamine receptors in the
      endothelium are unlikely modified after 12 weeks of diabetic development.

PMID- 9921405
TI  - Thrombomodulin levels in patients with coronary artery disease.
AB  - We investigated the association between the serum level of thrombomodulin and
      known coronary risk factors in 119 men who underwent coronary angiography. Total
      cholesterol level was significantly higher in patients with coronary
      atherosclerosis than in those without. Significantly higher frequency of
      hypertension was noted in patients with coronary atherosclerosis. Uric acid level
      and frequency of smoking tended to be higher in patients with coronary
      atherosclerosis but the differences were short short of the significant level.
      The serum level of thrombomodulin between patients with coronary atherosclerosis
      and those without was not statistically significant. Age, blood urea nitrogen,
      and creatinine were positively correlated and creatinine clearance was inversely
      correlated with the serum level of thrombomodulin. Serum levels of total
      cholesterol, triglyceride, high-density lipoprotein cholesterol, uric acid, and
      fasting blood sugar, plasma level of fibrinogen, and body mass index were not
      related to the serum level of thrombomodulin. There was no significant
      correlation between the severity of coronary atherosclerosis, hypertension,
      alcohol use, or smoking and the serum level of thrombomodulin. Restenosis was
      present in 8 of 16 patients who underwent percutaneous transluminal coronary
      angioplasty and had a follow-up angiogram at 6.0 +/- 3.0 months. Univariate
      analysis revealed no significant difference in the thrombomodulin level with and
      without restenosis. The present findings suggest that elevated thrombomodulin
      levels in patients with coronary artery disease may reflect retention of
      thrombomodulin due to decrease in thrombomodulin clearance in the kidney.

PMID- 9921406
TI  - Lipoprotein abnormalities in type 2 diabetic patients. Increased distribution of
      triglycerides (TG) in very low density lipoprotein (VLDL) and decreased
      apolipoprotein E/VLDL-TG ratio are risk for ischemic heart disease.
AB  - Plasma lipoproteins and clinical characteristics of type 2 diabetic patients with
      (n = 50) and without (n = 108) ischemic heart disease (IHD) were compared. The
      patients with IHD were older (64 +/- 9 vs 59 +/- 9 years, mean +/- SD, p < 0.01)
      and had a longer duration of diabetes (14 +/- 9 vs 11 +/- 8 years, p < 0.05).
      Lipids, lipoproteins and apolipoproteins were comparable in the two groups. The
      percent distribution of triglycerides (TG) in the very low density lipoprotein
      (VLDL) fraction was significantly higher (55 +/- 16 vs 50 +/- 17%, p < 0.05). The
      level of low density lipoprotein (LDL) (33 +/- 14 vs 39 +/- 15%, p < 0.05) and
      the apo E/VLDL-TG ratio (0.085 +/- 0.045 vs 0.120 +/- 0.097, p < 0.01), however,
      was significantly lower in patients with IHD than in those without IHD. Multiple
      regression analysis also indicated that age, duration of diabetes, percent
      distribution of TG in VLDL, percent distribution of TG in LDL and the apo E/VLDL
      TG ratio were significantly related to the presence of IHD. Hypertriglyceridemia,
      particularly when characterized by abnormalities of TG distribution, may play an
      important role in the development of IHD in type 2 diabetic patients.

PMID- 9921407
TI  - Leukocyte flow properties, polymorphonuclear membrane fluidity and cytosolic Ca2+
      content in subjects with vascular atherosclerotic disease.
AB  - In a group of subjects with monovascular atherosclerotic disease (MVAD) and in a
      group of subjects with polyvascular atherosclerotic disease (PVAD) we evaluated
      white blood cell (WBC) filtration (unfractionated, mononuclear -MN-,
      polymorphonuclear -PMN- cells), using the St. George Filtrometer and considering
      respectively the initial relative flow rate (IRFR) and the clogging rate (CR),
      the polymorphonuclear leukocyte membrane fluidity, employing the fluorescent
      probe 1.4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH) and calculating
      the fluorescence polarization degree, and the polymorphonuclear leukocyte
      cytosolic Ca2+ content, adopting the fluorescent probe Fura 2-AM. Only the
      filtration parameters (IRFR, CR) of unfractionated WBCs discriminate normals from
      MVAD and PVAD subjects, and also monovascular and polyvascular VAD subjects
      between them. The filtration parameters of mononuclear and polymorphonuclear
      leukocytes do not distinguish normals from MVAD and PVAD subjects. PMN membrane
      fluidity does not differentiate normals from MVAD and PVAD subjects, while PMN
      cytosolic Ca2+ content discriminates normals from MVAD and PVAD subjects, but
      does not distinguish the two groups of VAD subjects. In conclusion, in subjects
      with vascular atherosclerotic disease we noted an alteration of the
      unfractionated leukocyte flow properties, more evident in PVAD subjects, and an
      increase of the PMN cytosolic Ca2+ content.

PMID- 9921408
TI  - Vascular innervation in atherogenesis.
AB  - Although collar-induced atherosclerosis continues to be used as an investigative
      tool, the underlying mechanism has not been established. Two primary mechanisms
      suggested are adventitial ischemia due to reduction in vasa vasorum, and
      perivascular denervation. We have examined the effect of injuring the common
      carotid artery in the pattern produced by the ends of a silastic collar, and have
      correlated the effect on innervation with change in intima/media ratios in normal
      and cholesterol-fed rabbits. The serum cholesterol of cholesterol-fed rabbits was
      significantly elevated by 10 days following initiation of cholesterol feeding,
      and further elevated at 21 days. No structural difference was detected between
      the uninjured carotid arteries of control and cholesterol-fed rabbits. At the
      site of injury in freeze injured carotid arteries there was a thickening of the
      intima which was increased in cholesterol-fed rabbits. The intima at the site of
      injury was composed of lipid-laden cells embedded in a matrix of collagen and
      elastin fibres. In carotid artery segments, between two sites of freeze injury,
      denervation was established by immunohistochemistry and electron microscopy. The
      denervated segments were not morphologically different from uninjured carotid
      arteries in either control or cholesterol-fed rabbits. While injury induced
      intimal thickening and foam cell development, denervation did not. It is
      concluded that perivascular denervation is a consequence of silastic collar
      application and is not involved in the induction of atherosclerosis.

PMID- 9921409
TI  - The kinetics of cancer cells and of HIV1: the problems of cell and virus rebounds
      and of latency.
AB  - The kinetics of non treated and especially of treated HIV1 is compared to that of
      non treated and of treated cancer cells. Contrary to Skipper's scheme, based on
      constancy of cancer cell proliferation or post-chemotherapy decrease slope, the
      same chemotherapy successive cycles decrease in fact less and less the proportion
      of cell number reduction, and the hope of killing the "last cell" is a utopian
      concept. Hence, the very poor global benefit in cancer medicine registered in the
      last 50 years. The only cures are seen in child tumors and young adults testis
      cancer: the immunity reaction being stronger before 40 years of age than after 40
      may explain this difference with age. The a priori systematic opposition to
      active immunotherapy of cancer from some authorities has been a grave fault. Such
      fault should not be committed for the treatment of HIV1-AIDS complex. The
      continuous HIV1 so called intensive virostatic chemotherapy is complicated by
      severe toxicities, and resistances of relapses and virus re-activation when it
      must be discontinued. The widely accepted triple therapy only affects two virus
      targets (retro-transcriptase and virus protease), which is insufficient, as we
      have shown. We have also observed that the constant and most rapid VL decrease to
      < 200 or < 20 RNA copies/mL is obtained when four virus targets are affected,
      including some concerning DNA provirus (which is the case of acriflavine and
      methylhydroxy-ellipticine). As in acute lymphoid leukemia, two treatment phases
      can be distinguished: a) the VL reduction to 20 copies; b) the maintenance of the
      residual < 20 copies of viruses. Excellent results as far as VL decrease and
      maintenance at < 20 copies have been obtained with a follow-up between 1 1/2 and
      6 years, without any toxicity nor global resistance, with combinations of four
      drugs affecting four viral targets, applied in short (3 week) sequences,
      different from each others owing to drug rotation. This can be compared with the
      65% remission rate obtained with alternative different cycles of cancer
      chemotherapy in tumors resistant to conventional modalities. The possibility of
      repeating for ten patients the evaluation of viral load and of immunologic
      parameters has allowed us to discover that some VL decrease curves are fractal.
      As well, maintenance 20 copies are not rarely interrupted by short and reversible
      HIV1 rebounds as those we had described in "cured" acute lymphoid leukemia
      patients. Of utmost importance, all HIV1 rebounds were associated with the
      presence of one cofactor: chimerism, chronic hepatitis, CMV, herpes 8, herpes 6,
      and influenza are those we observed. The problem today is not to "kill the last
      tumor cell in cancer" or "the last HIV1 particle" in HIV1-AIDS complex. It is to
      keep the residual cells or virus in latency. Active immunotherapy and other
      biologic interventions, such as hypermethylation, should be studied in this aim,
      as they are also able to do so.

PMID- 9921410
TI  - Structure and function of HIV-1 and SIV Tat proteins based on carboxy-terminal
      truncations, chimeric Tat constructs, and NMR modeling.
AB  - To further define the structure and function of the domains in HIV-1 and SIV Tat
      proteins, chimeric Tat cDNA expression constructs were generated with crossover
      points at the carboxy-terminal end of the cysteine rich domain. The chimera
      containing the amino-terminal region of SIV and carboxy-terminal region of HIV
      exhibited activity similar to HIV-1 Tat and SIV Tat on both the HIV-1 and SIV
      LTRs. In contrast, the reciprocal chimera functioned poorly. As determined by the
      activity of carboxy-terminal truncation mutants, the region immediately
      downstream of the basic domain is critical for efficient transactivation by HIV-1
      Tat, but not SIV Tat protein. In this report, we present a model for Tat domains
      based on NMR data and the known functional properties of Tat protein. According
      to our modeling two sites for protein : protein interactions are present in HIV-1
      and SIV Tat proteins. Site I, which is presumably involved in cyclin T binding,
      is similar in both HIV-1 and SIV Tat proteins as well as in Tat chimeras. Site
      II, however appears structurally different in HIV-1 and SIV Tat models, although
      in both cases is comprised of amino and carboxy-terminal residues. Differences in
      Site II may thus account for the differential activities of HIV-1 and SIV Tat
      carboxy-terminal truncations. Site II in the poorly active chimera differs
      significantly from that found in HIV-1 and SIV Tat proteins. The two site
      structural model presented here may have important implications for the role of
      Tat in HIV pathogenesis and may provide insights for the design of Tat vaccines
      and targeted therapeutics.

PMID- 9921412
TI  - Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines
      (DARC).
AB  - The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of
      erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as
      interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on
      activation, normal T cell-expressed and -secreted (RANTES), but not macrophage
      inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been
      identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium
      knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian
      individuals via DARC making RBCs able to transmit HIV to peripheral blood
      mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is
      inhibited by treating these cells with recombinant RANTES, but not with
      recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding
      suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the
      entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.

PMID- 9921411
TI  - A prophylactic and therapeutic AIDS vaccine containing as a component the
      innocuous Tat toxoid.
AB  - Extracellular Tat can act as a viral toxin on uninfected cells of different
      tissues, including the CNS and the immune system, thus in order to immunize
      humans against Tat we have prepared a biologically inactivated but immunogenic
      Tat (Tat Toxoid). Tat Toxoid is not toxic in mice even at high doses. It triggers
      high levels of specific Tat Abs in the mouse and rabbit. Furthermore, in humans
      Tat Toxoid immunization was safe and induced in seronegatives persistent high
      levels of Tat Abs and in immunodeficient patients a significant rise of these
      specific Abs. Facing acute HIV-1 infection, the presence of high level of
      circulating Tat Abs promoted by Tat Toxoid vaccine should prevent Tat-induced
      immunosuppression and allow anti-HIV-1 cellular response to develop. As a
      consequence, early release of beta-chemokines could enhance host resistance
      towards HIV-1, and, in infected people, inhibit viral replication and evolution
      towards AIDS.

PMID- 9921413
TI  - Epidemiology, etiology and pathogenesis, clinical presentations and therapeutic
      approaches in Kaposi's sarcoma: 15-year lessons from AIDS.
AB  - Kaposi's sarcoma (KS) is a leading cause of morbidity among 25-30% of AIDS
      patients and is by far the most common AIDS-associated malignancy. Since the
      beginning of the 1990s the incidence of KS continuously declined, but it was the
      introduction of protease inhibitors that markedly reinforced this phenomenon. In
      our experience, the annual incidence was 59/1,000 patient-years in 1984 vs
      21.2/1,000 patient-years in 1990, 12.5/1,000 patient-years in 1996, with a drop
      to 3.2/1,000 patient-years in 1997. One of the peculiar characteristic of this
      tumor is the sexual susceptibility, which could be the consequence of a hormonal
      protection in females. The in vitro models of KS-like cell culture promoted and
      sustained in vitro with a conditioned medium containing several pro-inflammatory
      cytokines, the characterization of human herpes virus-8 (HHV-8) in almost all the
      cases of AIDS-KS as the putative KS-agent and the determination of a putative
      role of hCG-associated factors in the control of KS growth are among the leading
      discoveries of this last decade in this field.

PMID- 9921414
TI  - Effect of RANTES on the infection of monocyte-derived primary macrophages by
      human immunodeficiency virus type 1 and type 2.
AB  - The effect of beta chemokines on human immunodeficiency virus type 1 (HIV-1)
      infection of primary macrophages is controversial, and their effect on HIV-2
      infection of these cells has not yet been documented. We examined the effect of
      synthetic and recombinant regulated-on-activation, normal T cell-expressed and 
      secreted (RANTES) on HIV-1 and HIV-2 infection of primary monocyte-derived
      macrophages (MDM) that were obtained as the adherent cells of 5-day cultures of
      blood mononuclear cells (PBMC), followed by 2-day culture without peripheral
      blood mononuclear cells (PBMCs) nor added cytokines. These MDM expressed CD4,
      CCR5 and CXCR4, the major coreceptors for HIV macrophage- and T cell-tropic
      isolates, respectively. Infection of MDM from different donors with HIV-1 or HIV
      2 macrophage-tropic strains was reproducibly inhibited by RANTES. This inhibition
      depended on RANTES continuous presence in culture during and after infection.
      Treatment of MDM with RANTES just before or during, but not after, exposure to
      virus did not protect MDM from infection. When RANTES was added after MDM had
      been infected, and was continuously maintained in culture thereafter, no
      inhibition occurred and limited enhancement of infection could be observed. These
      data indicate that RANTES inhibits HIV-1 as well as HIV-2 infection of MDM,
      likely at a post-binding step, and support the role of CCR5 as the major
      coreceptor for HIV-1 and HIV-2 entry into primary macrophages.

PMID- 9921415
TI  - Effect of dietary supplementation with zinc sulphate on the aging process: a
      study using high field intensity MRI and chemical shift imaging.
AB  - High field intensity magnetic resonance imaging (HF-MRI) has been applied to the
      in vivo study of age-related processes of organs located in the cervical-thoracic
      region in mice and to describe the effects of oral zinc supplementation on these
      processes. Spin-echo (SE) pulse sequence and chemical shift imaging (CSI)
      techniques have been used. Aging produced a progressive reduction of muscular
      masses and of thymic area, whereas the HF-MRI appearances of spinal cord and of
      salivary glands were unchanged. In some aged animals, subcutaneous fat was
      reduced while visceral fat was well developed. In the group of old animals
      supplemented with zinc sulphate, muscular masses were more developed than that of
      the group of untreated old animals. Oral zinc supplementation also produced an
      enlargement of the adipose tissue and the thymic area showed an increase of about
      65% compared with thymic area measured in the group of old animals used as
      controls. The present study confirms previous data about the effects of Zn
      supplementation on aging processes and demonstrates that HF-MRI is a powerful
      technique to study processes of aging, providing information about the effects of
      drug treatments on these processes.

PMID- 9921416
TI  - Interaction of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+
      signaling.
AB  - Interactions of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+
      signaling were elucidated in Chinese hamster ovary (CHO) C1 cells, which
      transfected a control vector without any expression of the Na(+)-Ca2+ exchanger's
      gene while CHO CK1.4 cells transfected an expression vector encoding the bovine
      cardiac Na(+)-Ca2+ exchanger's cDNA, treated with lithium- or sodium-buffer
      medium respectively, by using L16(2)15 multifactorial orthogonal statistics and
      fura-2 fluorescence real-time imaging. In contrast to controls of Li(+)-treated
      C1 cells, the store-dependent Ca(2+)-influx (SDCI) was enhanced by either the
      Na(+)-Ca2+ exchanger, Na(+), 1-?(beta-[3-(4-methoxyphenyl)propoxy]-4
      methoxyphenethyl?-1H-imidazole HCl (SK&F96365) or ouabain, and by interactions of
      the Na(+)-Ca2+ exchanger with either Na+, SK&F96365 or both SK&F96365 and
      ouabain; and ATP-induced Ca2+ release (AICR) was activated by SK&F96365 or Na+
      alone, interactions of the Na(+)-Ca2+ exchanger with SK&F96365 or Na+, and an
      interaction between SK&F96365 and ouabain. The dramatic interaction of the Na(+)
      Ca2+ exchanger with small molecules indicates that cell Ca2+ signaling is
      generated by inositol triphosphate (InsP3)-dependent pathways, allosteric effects
      of the G-protein coupled P2y&2u purinoceptor and multi-site recognition. Our
      findings provide meaningful clues for designing new strategies of cardiocerebral
      vascular oxidative diseases.

PMID- 9921417
TI  - Disclosing special needs to parents. Have we got it right yet?
AB  - Parents' perceptions of how they were told that their child has special needs
      were examined. Thirty-nine families on the Isle of Wight completed a structured
      interview. Participants formed two groups. The first group comprised of 23
      families who had a child aged from birth to 5 years with special needs. In the
      second group there were 16 families who had a child aged between 15 and 20 years
      with special needs. Parents were asked about their perceptions of how their
      child's special needs were disclosed, their satisfaction with how they were told
      and what improvements they would have liked. Differences between the two cohorts
      were examined, and changes in how services were perceived were investigated.
      Overall, parents in the group with younger children were more satisfied about the
      way in which they were told that their child had special needs than those with
      older children. Implications for service delivery and future research are
      considered.

PMID- 9921418
TI  - Enabling children: participation as a new perspective on child-health promotion.
AB  - As fellow citizens, all children need a stimulating social environment that helps
      them develop self-respect and social competence. Developmental research, however,
      shows, that many children do not or cannot fulfil the social, moral or cognitive
      developmental tasks which are necessary for healthy development. A lack of
      opportunities for gaining meaningful social experiences can be seen as a major
      source of psychosocial and behavioural problems in children. On the contrary,
      active commitment in educational environments such as the school and the
      neighbourhood, helps them to get an increasingly better grip on their own lives
      and health. Moreover, such 'children's participation' appears to have a
      protective and preventive effect for health-related problems. Therefore, it is
      argued, that 'enablement', a key-element of both the Ottawa Charter on Health
      Promotion and the International Convention on the Rights of the Child, should be
      at the core of every child-health promotion programme.

PMID- 9921419
TI  - What is community-based rehabilitation? A view from experience.
AB  - This paper argues that unless community-based rehabilitation (CBR) programmes
      acknowledge the complexities of working in diverse communities with their unique
      cultural, religious, social and economic conditions, they will not be able to
      meet the needs of service provision for people in developing countries. An
      examination of some of the main aspects that form the essential components of
      CBR, the realities of the manner in which they interact, and the way they should
      interact is presented from experiences of CBR services initiated by the Spastics
      Society of Eastern India, in West Bengal, India.

PMID- 9921420
TI  - Assessment of parents and young children (Children Act 1989)--a child
      psychotherapy point of view.
AB  - The criteria used by professionals in assessing child care cases are not always
      made explicit, partly because of the ambiguity of the terms 'vulnerability' and
      'at risk'. This paper presents a child psychotherapy view of what professionals
      may look at in terms of the interactions between parent and young child and how
      these may be understood. 'Reasonable expectations' of child development and
      parental care are considered. In terms of the child, overall attachment and
      communication needs and the specific developmental phase in terms child's
      maturing cognitive and socio-emotional functions are emphasized. In terms of the
      parent, the capacity to see the baby as separate from their own internal
      conflicts and to reflect upon the infant's mental state are seen to be pivotal to
      the infant's psychological well-being. The authors discuss the unconscious re
      enactment of malignant patterns from the past through the relationship with the
      baby, and why parents are sometimes unable to avoid this. Finally, the authors
      suggest that assessment of the capacity for change in vulnerable parent-infant
      constellations must take into account the baby's developmental timetable.

PMID- 9921421
TI  - Using a model of transactional developmental regulation to evaluate the
      effectiveness of an early intervention programme for pre-school children with
      motor impairments.
AB  - This study investigates how early intervention programme benefits may operate
      beyond the traditional parameters of child developmental progress by exploring
      family outcomes too. Sameroff and Fiese's (1990) model of transactional
      developmental regulation is applied to provide a conceptual framework for the
      evaluation of an interdisciplinary intervention programme for pre-school children
      with motor impairments. Qualitative and quantitative methods were combined by
      using standardized assessment of child progress and interviews. Fifteen children,
      11 mothers and five staff participated in the study. Triangulation of data was
      carried out to obtain evidence of remediation (child progress), re-education
      (parent learning) and redefinition (changes in parental perceptions and
      expectations of their child's difficulties that allowed parents to apply usual,
      rather than special, caregiving practices) as described in Sameroff and Fiese's
      model. Findings point to the effectiveness of the programme as indicated by
      evidence of child developmental progress, parental re-education and redefinition.
      The study suggests that redefinition may be at least as important a programme
      outcome as remediation or re-education, challenging established notions of the
      goals of pre-school programmes for disabled children. Implications of a broader
      based, family-focused approach are discussed.

PMID- 9921422
TI  - The pediatric airway. 1962.

PMID- 9921423
TI  - Signs of depth and danger. 1962.
AB  - A large proportion of the serious complications that occur during pediatric
      anesthesia are caused by failure to recognize early signs of danger. The greatest
      dangers include excessive anesthetic depth, respiratory obstruction and
      depression, acid-base derangement, shock, myocardial depression, and extreme
      alterations in body temperature. Simple monitoring devices, including the
      anesthetic chart, stethoscope, blood pressure cuff, and thermometer, are
      essential in all major pediatric procedures. Use of the stethoscope should never
      be omitted in any case. Signs of cardiorespiratory and neuromuscular activity
      characteristic of infants and children should be familiar to all anesthetists who
      engage in pediatric work.

PMID- 9921424
TI  - Intercostal nerve block. 1963.

PMID- 9921425
TI  - Choice of agents for spinal anesthesia. 1963.

PMID- 9921426
TI  - Spinal anesthesia for cesarean section. 1963.
AB  - Safety in spinal anesthesia for cesarean section is achieved by strict adherence
      to the cardinal principles of proper evaluation and selection of patients, the
      use of prophylactic vasopressors, preanesthetic establishment of a reliable
      intravenous channel, small doses of the local anesthetic, close monitoring and
      maintenance of systolic blood pressure above 100 mm. Hg, and avoidance of ergot
      compounds in the presence of vasopressors.

PMID- 9921427
TI  - Cyclopropane. 1963.
AB  - Special precautions are stressed for cyclopropane, not because they are uniquely
      required for this drug, but because failure to observe them is apt to result in
      the more rapid occurrence of disaster for the patient. Strict attention to every
      minute detail is absolutely essential for good, safe cyclopropane anesthesia.
      Most important of all is adequate ventilation. Practically, this means assisting
      or controlling the ventilation at all times. Constant monitoring of the
      precordial heart tones is also mandatory. The blood pressure must be checked
      frequently, especially when the level of anesthesia is being deepened. In
      addition to all the required antiexplosion precautions required in operating
      rooms, we also recommend the use of a wet towel grounding as an added precaution.
      The anesthesiologist should further protect himself and the patient by keeping
      everything around the head of the table at the same electrical potential by
      frequently touching the various items. He should maintain constant contact with
      the patient whenever possible. The anesthesiologist should train himself to take
      these precautions automatically, so that they will not be omitted during trying
      circumstances. Our experience has been that residents trained to administer good,
      safe cyclopropane anesthesia according to the principles enunciated usually are
      much more attentive to details with other techniques. Constant observation of the
      patient and the progress of the surgery is also necessary, if good cyclopropane
      anesthesia is to result. Finally, there are some guiding principles that I
      believe are essential for the conduct of good, safe cyclopropane anesthesia. 1.
      Be thoroughly familiar with the pharmacological actions of the drug. 2. Maintain
      a healthy respect for the potency of the drug, but no fear. 3. Be especially sure
      to maintain adequate ventilation through a patent airway. 4. Remember the drug is
      explosive. 5. Be eternally vigilant to the minute details of the conduct of the
      anesthesia. 6. This drug is for the real "pro," not the amateur. It is to be
      handled with the finesse of the violinist, not with the banging of the cymbal
      player. 7. Answer for yourself the question, "If this drug is so frequently
      selected for the very poor risk patient, wouldn't it be equally good or better
      for the healthy patient?".

PMID- 9921428
TI  - Halothane. 1963.

PMID- 9921429
TI  - Diethyl ether. 1963.

PMID- 9921430
TI  - Atrial activity and anesthesia. 1963.

PMID- 9921431
TI  - Intravenous anesthesia--Chairman's opening and closing remarks. 1962.

PMID- 9921432
TI  - Respiratory factors in the uptake and excretion of anesthetics. 1965.
AB  - We have considered some of the ways in which respiration can affect the gas
      exchange process. The simplest relationships are purely physical and relate to
      the speed with which the lung and tissues can be filled or emptied. More complex
      relationships involve a consideration of the interplay between blood and gas in
      the lung and the effects of gas exchange on respiratory volumes themselves.
      Finally, some examples of the importance of physiologic alteration produced by,
      and producing respiratory shifts during, gas uptake processes were presented
      briefly. The detailed interpretation of gas exchange phenomena demands more
      quantitative information of this sort, concerning not only the respiratory but
      the circulatory and tissue level variations affecting uptake during anesthesia.
      Nevertheless, understanding of the principles and application of such data as are
      available can go far toward removing the handicaps of empirical practice from the
      day-to-day administration of anesthetic agents to human beings.

PMID- 9921433
TI  - Alveolar-arterial PO2 differences in anaesthesia. 1966.
AB  - During routine anesthesia, normal arterial oxygenation cannot be ensured by
      observation of the patient or by any practicable measurement technique. It is
      therefore essential to have an understanding of the factors which influence the
      arterial PO2. The factors influencing the alveolar PO2 are simple and the actual
      level may be predicted with considerable accuracy. However, the arterial PO2
      cannot easily be predicted because of the large and variable alveolar-arterial
      PO2 differences which occur during anaesthesia. Measurement of alveolar-arterial
      PO2 difference during anaesthesia requires the calculation of the ideal alveolar
      PO2 by an equation which allows for the fact that inert gas is seldom in
      equilibrium under these circumstances. Analytical techniques must be selected for
      their freedom from interference by anaesthetic gases. Alveolar-arterial PO2
      differences encountered in routine surgical patients correspond to a calculated
      venous admixture within the range 5-25 per cent of total pulmonary blood flow.
      Somewhat higher values are encountered when the alveolar PO2 falls below 120
      mm.Hg. It is not possible to foresee those patients who develop extensive venous
      admixture. It is probable that the principal component of the venous admixture is
      blood flow through atelectatic lung, although its recognition by radiography is
      difficult. It is often possible to reduce the alveolar-arterial PO2 difference by
      hyperinflation of the lung.

PMID- 9921435
TI  - [Contrast hysterosonography: an efficient means of investigation in gynecology.
      Review of the literature].
AB  - Contrast-enhanced vaginosonography constitutes a new way of imaging the uterine
      cavity. Real time transcervical injection of sterile saline in the uterine cavity
      (saline infusion sonography, SIS) allows to precisely visualize numerous
      intrauterine pathologies such as endometrial polyps, myomas, intrauterine
      adhesions and various anatomical malformations. We introduced the technique of
      saline infusion sonography in October 1996 for the evaluation of endouterine
      pathologies. In this review article, we will describe the technique of contrast
      sonography, its indications, contraindications and semiology, the practical
      problems to be solved and its performances.

PMID- 9921434
TI  - Postoperative hepatic dysfunction in perspective. 1970.
AB  - Postoperative hepatic dysfunction will remain a difficult entity to place in
      perspective until increased data are obtained from prospective clinical trials.
      Ideally these data should compare hepatic dysfunction not only to other
      postoperative complications, both with regard to overall incidence and to
      mortality, but also to the overall risks of anesthesia and surgery. The
      contribution of drug-induced hepatic damage to postoperative hepatic dysfunction
      has remained unsettled since chloroform was first incriminated during the
      nineteenth century. The drug was condemned in 1912, without any attempt being
      made to determine the incidence of the so-called delayed chloroform poisoning,
      with the result that the drug is still in use and the chloroform controversy
      remains unsettled to this day. The halothane controversy is also unsettled and
      currently overshadows the former controversy, although academically of no greater
      importance. Although not an anesthetic, cincophen is another drug about which
      there is controversy concerning its hepatotoxic potential. Babior and Davidson
      noted that it was the first drug implicated in hepatic necrosis--presumably with
      the exception of chloroform--the first report appearing in 1922. In 1941 the
      Council on Pharmacy and Chemistry of the American Medical Association concluded
      that the case against cincophen was not proved and that an urgent need existed
      for controlled clinical studies. Twenty-five years later Babior and Davidson
      noted that such studies had still not been undertaken and that the situation was
      the same as it was a quarter of a century earlier. Perhaps the time has come for
      a prospective, randomized, controlled clinical trial to be undertaken so as to
      evaluate the hepatotoxicity of one of these drugs. Perhaps an anesthetic agent
      such as halothane, concerning multiple administrations of which there is
      currently serious question, would be a suitable choice for such a study. The drug
      is in wide use today, partly because of evidence of satisfactory death rates
      following its administration, but also because on the basis of much excellent
      physiological data--but an almost total lack of any confirmatory epidemiological
      evidence--it is thought to contribute positively toward a low overall incidence
      of postoperative morbidity. Perhaps in addition, as a corollary, the time has
      come when, as attempts to illuminate a well--enunciated problem of this nature-
      that is, to test a clearly formulated hypothesis--the isolated case report, the
      collection of isolated case reports, the series of patients reported in the
      absence of a proven comparable control group, and the uncontrolled survey, should
      be "laid to rest." At best they provide only additional hypothesis-formulating
      information. At worst, however, they give increased exposure to a suggestion
      concerning cause and effect upon which physicians may act to their patients'
      detriment if the hypothesis ultimately proves to be erroneous. MacMahon et al.
      have stated that although there is no clear-cut dividing line between descriptive
      and analytical epidemiology, most epidemiological studies can indeed be
      classified primarily as either hypothesis-formulating or hypothesis-testing. Just
      as we have conducted the definitive retrospective hypothesis-testing study--the
      National Halothane Study--demanded by the "halothane hepatitis" controversy, so
      must we now move to the final stage of epidemiological investigation
      (experimental epidemiology) by investigating the effects of multiple
      administrations of the drug. On this point the National Halothane Study acts more
      as a hypothesis-formulating study than as a hypothesis-testing study. Hill has
      noted that statistical problems must be dealt with by the statistical method.
      (ABSTRACT TRUNCATED)

PMID- 9921436
TI  - [Management of premature rupture of membranes in a monofetal pregnancy before 28
      weeks gestation].
AB  - To establish appropriate management of premature rupture of the membranes before
      28 weeks, we examined maternal and fetal risks in pregnancies complicated by this
      rare problem (1-7/1000). Three main factors were identified in such
      circumstances: prematurity, infection and oligohydramnios. Prematurity is
      inevitable and depends on three factors: gestational age at rupture of the
      membranes which is an independent predictor of poor prognosis before 22 weeks;
      gestational age at delivery as neonates born before 26 weeks gestation have an
      overall perinatal survival < 50%, and latency period between preterm rupture of
      the membranes and delivery which ranged from 1 to 161 days with a mean 7.8 days.
      Infection is the second factor with a high incidence (> 30%) of chorioamnionitis.
      The third factor is skeletal deformations and pulmonary hypoplasia predicted by
      severe and prolonged (> 14 days) oligohydramnios. Only about 40% of such women
      will take home a live baby. Successful outcome can be achieved in about 60% of
      these survivors. Termination of pregnancy is warranted at 22 weeks gestation or
      less and may be proposed. Beyond 22 weeks gestation, management is based on a
      wait-and-see attitude with ultrasonographic and bacteriological surveillance.
      After 25 weeks gestation, management becomes more active with use of antibiotics,
      tocolytics and steroids which can help prolong the latency period and improve
      fetal outcome. Ongoing counselling and psychological support are essential in the
      management of this morbid complication of pregnancy.

PMID- 9921437
TI  - [Analysis of medical catalog terms using the MAOUSSC model: application to
      Gyncecology-Obstetrics].
AB  - BACKGROUND: The Model of Assistance and Orientation of a User within a System of
      Coding (MAOUSSC) used to describe activity in human medicine was used to analyse
      French medical nomenclature in Gynecology and Obstetrics. METHODS: French medical
      nomenclature for gynecology and obstetrics was translated with the multiaxial
      model (MAOUSSC) to allow critical analysis. RESULTS: All the 119 medical acts in
      the French nomenclature involving the female genital tract and obstetrics could
      be translated with the model. 24% of the acts were imprecise, ambiguous or
      implicit: the nature of the procedure was not explicit in 7 cases, the surgical
      route was not given in 86 and the surgical instrumentation not named in 75.
      Activities involving numerous medical specialties and ambulatory activity can be
      described with the MOUSSC model. CONCLUSION: The MAOUSSC model is still in the
      experimental stage. It is however easy to implement, has a high potential for
      describing various medical acts and is suitable for the description of
      gynecological and obstetrical activity both in terms of economical and medical
      efficacy.

PMID- 9921438
TI  - [Can we and must we organize cervical cancer screening in France? Results of the
      pilot project "EVE" in the department of Bas-Rhin].
AB  - EVE is a pilot project for cervical cancer screening whose aim is to test the
      feasibility of organized screening in the French liberal health system with a
      consensus of medical participants. After three and a half years, 74.8% of women
      aged 25 to 64 had had at least one smear. Coverage varies with age, from 89%
      between 25 and 29 to 56% between 55 and 60. Only 8% of smears are taken by
      General Practitioners. There is a tendency to space out smears because only 14%
      of women had had a second smear within one year and 41.1% within 2 years. On the
      other hand more then 20% percent of women do not return after 3 years.
      Pathological smears represent 1.94% of all smears. For these, a questionnaire is
      sent to the physician in order to get information on follow-up. This enables
      cytologic/histologic correlation. The histologic exam reveals a pathological
      lesion in 95% of cytologies consistent with invasive cancer, 91% of those
      consistent with high grade lesions and 70% of those consistent with low grade
      lesions.

PMID- 9921439
TI  - [Medical responsibility of midwives in public and private maternity units.
      Results of a survey of 11 French regions].
AB  - OBJECTIVE: To describe medical responsibilities of midwives in maternity units
      and to compare these responsibilities between categories of maternity units.
      METHOD: A mail survey was carried out in 1996 on a random sample of midwives. The
      analysis was based on 884 midwives providing antepartum, perpartum or postpartum
      care in public or private maternity units. RESULTS: For many procedures and
      decisions, medical responsibilities of midwives were more important in the public
      sector than in the private sector. Responsibilities were more extended in
      university hospitals than in other public hospitals. These differences were
      observed in the postnatal ward, in the antenatal ward, and for some specific
      tasks in the labor ward. In the private sector, responsibilities varied according
      to the status of the maternity unit: midwives performed fewer procedures in
      profit-based maternity units than in non-profit ones. CONCLUSION: The roles of
      midwives vary from one type of maternity unit to another, but differences are
      also observed within the same categories of units. Consensus on what are the
      medical responsibilities of midwives does not exist in a variety of situations,
      even with regard to the management of normal pregnancies and deliveries.

PMID- 9921440
TI  - [Obstetric complications of the first trimester in Western Africa].
AB  - The obstetrical complications affecting women in Benin, Senegal and Ivory Coast
      during the first trimester of pregnancy were studied. Information about the 345
      women included in the study was collected from registers maintained by the eight
      participating maternity units. The most frequent complications observed were
      spontaneous abortions (50% of admissions), complications of induced abortions
      (34%), and ectopic pregnancy (8%). Overall, the patients appear to have gained
      rapid access to care: two thirds of the women underwent interventions on the day
      of admission. Nevertheless, there were three maternal deaths, two of which
      followed induced abortion complications.

PMID- 9921441
TI  - [RT-PCR in the prenatal diagnosis of rubella. Report of 2 cases].
AB  - OBJECTIVE: To confirm the interest of the reverse transcription-coupled
      polymerase chain reaction (RT-PCR) in prenatal diagnosis of rubella. PATIENTS AND
      METHODS: Maternal blood, amniotic fluid and foetal blood specimens collected at
      21 to 24 weeks of amenorrhea from two pregnant women with serologically proven
      rubella infection were tested by RT-PCR and cell culture for detection of rubella
      virus. Rubella virus-specific IgM antibodies were also assayed in foetal blood.
      RESULTS: In both cases, rubella virus was detected in foetal blood by RT-PCR and
      cell culture, whereas it was not detected in maternal blood. Rubella virus
      specific IgM were also detected in foetal blood. In amniotic fluid specimens,
      rubella virus was detected by RT-PCR in one case and by cell culture in the other
      one. A termination of pregnancy was carried out in both cases. COMMENTS: RT-PCR
      is a rapid test. It could be useful to confirm foetal infection and could
      represent a criterion for considering a pregnancy termination. However, this
      technique which is not yet standardized for detection of rubella virus, needs
      further validation by additional studies.

PMID- 9921442
TI  - [Vaginal metastases of breast cancer].
AB  - Metastases to the vagina from breast carcinoma are uncommon, and are most often
      detected during autopsies of patients who have died from a breast cancer or from
      metastases to the genital tract. A case of symptomatic vaginal metastasis
      secondary to bilateral breast carcinoma is reported. The potential routes of
      dissemination include lymphatic and vascular spread. Their respective frequencies
      vary in the literature. Lymphatic spread in this case is suggested by
      demonstrable ovarian, myometrial, and lymph node involvement associated with
      massive submucosal vaginal involvement. This observation of concomitant visceral
      and lymphatic spread improves our knowledge of metastatic spread from breast
      cancer to the female genital tract by the lymphatic route.

PMID- 9921443
TI  - [Color Doppler in the prenatal diagnosis of umbilical cord hernia].
AB  - Pathologies of the fetal ventral abdominal wall are easily diagnosed by antenatal
      ultrasonography. The most common anomalies are omphalocele, often associated with
      other malformations or chromosomal abnormalities, and gastroschisis. We describe
      an antenatal diagnosis of umbilical cord hernia which could be confirmed by color
      Doppler. This entity is important to know not to put the umbilical clamp on a
      bowel loop after delivery.

PMID- 9921444
TI  - [Pelvic hemangiopericytoma in pregnancy. Report of a case].
AB  - We report a case of pelvic retroperitoneal hemangiopericytoma (HPC) discovered
      early during pregnancy. Preoperative diagnosis was obtained by a transvaginal
      biopsy. Treatment consisted of therapeutic abortion, excision surgery and
      radiotherapy. In the follow-up examination 32 months after operation, no evidence
      of tumor recurrence was found. This is the second reported case of HPC
      complicating pregnancy.

PMID- 9921445
TI  - [Importance of early management of puerperial psychosis. Report of a case].
AB  - Recent reports have demonstrated that puerperal psychosis is preceded by
      prodromic signs. These signs must be recognized in a multidisciplinary context,
      opening the way to improved diagnosis, therapy and prognosis. On the basis of our
      clinical experience, we stress the important of early management in women who
      present prodromic signs of puerperal psychosis. Specific management relies on
      intensive psychotherapy with daily sessions centered on filiation. With this
      approach, the emergence of delusions can generally be prevented, usually allowing
      an uninterrupted mother-infant relationship. We hypothesize that this approach
      has a favorable influence on later mother-child interactions and cause profound
      changes in the mother's psychic organization, resulting in a better long-term
      prognosis. We illustrate our point with a case report.

PMID- 9921446
TI  - [Should PACS be developed?].

PMID- 9921447
TI  - [Economic and organizational evaluation of an imaging network (PACS)].
AB  - OBJECTIVE: Over the last twenty years, imaging modalities featuring new image
      production methods (ultrasound, nuclear magnetic resonance, etc.) have appeared
      on the market. Nevertheless, conventional radiology still accounts for 70% of the
      image examinations carried out in most western countries, including France. The
      conventional radiological image is in the process of evolving from analog to
      digital form. Digitalization of radiology means that image acquisition, archiving
      and distribution functions that were previously carried out by hand can now be
      automated using a Picture Archiving and Communication System. Decision-makers are
      having to decide whether or not to promote the development of PACS which, while
      they considerably modernize the way in which images are managed, also require
      heavy capital outlays. METHOD: A critical appraisal of the literature allowed us
      to evaluate the relative cost and the efficiency of these image networks in
      comparison with film-based archiving and communication systems. RESULTS: It is
      clear from the economic evaluation that a PACS strategy involves greater costs
      than a film system. While PACS systems do generate savings on film and on storage
      space and obviate the need for certain staff, these savings do not offset the
      extra equipment and maintenance costs. This situation is likely to persist for
      some years yet, even when future price reductions are taken into account. The
      objective of this new radiological information management method is to improve
      organizational efficiency and hospital productivity. However, the economic
      evaluations that have been published to date are cost studies which do not take
      the efficiency criterion into account. A number of potential organizational
      benefits such as the fact that medical decisions can be made more quickly or that
      the average length of hospital stays can be reduced, are often claimed for PACS.
      However, for methodological reasons, these results cannot be generalised to cover
      all PACS. It is difficult to compare PACS and film systems because the PACS
      technology is continuously evolving and because each PACS is specific to a site.
      CONCLUSION: After having weighted these different points, the ANAES has made the
      following recommendations concerning the development of PACS. A strategic
      analysis should be carried out before any decision is made to install a PACS.
      Moreover, hospitals will have to define the precise functions of their PACS in
      relation to the objectives of their medical project and each network must be
      configurated coherently.

PMID- 9921449
TI  - [Computed tomography of lymphoma in adults. The Study Group of Lymphoma in
      Adults].
AB  - In order to avoid misinterpretation especially at the initial imaging procedure
      as well as on follow up CT, the authors illustrate the features of the multiple
      nodal and extranodal localisations of lymphoma. The evolutive findings are
      emphasized.

PMID- 9921448
TI  - [Diagnostic prenatal ultrasonography of malformations of the fetal anterior
      abdominal wall].
AB  - Abdominal wall defects include a broad spectrum of structural malformations with
      variable severity and prognosis. The purpose of prenatal ultrasound examination
      is to correctly diagnose and classify these malformations according to their
      localization (particularly their relation to the umbilical cord insertion), their
      contents, their size and associated malformations or karyotypic abnormalities.
      Based on this examination, two groups can be distinguished: gastroschisis or
      omphalocele (when the latter is isolated, in particular without karyotypic
      abnormalities) which can be surgically corrected at birth, and for which
      predictive criteria of outcome must be evaluated (vitality of herniated bowel,
      size and contents of omphalocele); severe malformations (ectopia cordis, cloacal
      exstrophy, Beckwith-Wiedemann syndrome, short umbilical cord, amniotic band
      syndrome) for which pregnancy termination could be proposed.

PMID- 9921450
TI  - [Radiologic aspects of infarction of the appendix epiploica].
AB  - Clinical, US, CT and MR findings were reviewed in 5 patients with primary
      epiploic appendagitis (3 men, 2 women, mean age 38 years, age range 29-62 years)
      seen between December 1994 and December 1997. Diagnosis was reached in all cases
      with CT, with US in 3 and with MR in 1. Follow-up CT was performed in 2 cases and
      clinical follow-up in 4. One patient underwent surgery. Initial US, CT or MR
      examinations revealed a fatty oval-shaped nodule located anteriorly or
      anterolaterally to the left colon. The greater diameter ranged from 20 to 30 mm.
      Perinodular lesions with strands of periappendicular fat and thickened parietal
      peritoneum were visualized in all cases without any other inflammatory process in
      the abdomen. Symptoms resolved within 4 days in all patients. Signs of fatty
      inflammatory processes resolved in the 2 patients who had follow-up CTs. Primary
      epiploic appendagitis has characteristic US, CT and MR features which help guide
      medical treatment.

PMID- 9921451
TI  - [Evaluation of a new MRI cholangiography sequence with a half-Fourier acquisition
      technic].
AB  - PURPOSE: The aim of this study was to evaluate a new MR cholangiography sequence
      in which thick slices are obtained with half Fourier acquisition (SSFSE) in
      biliary obstructive diseases. PATIENTS AND METHODS: Fifty patients with suspected
      bile duct obstruction were prospectively investigated with MR cholangiography
      using SSFSE sequence with thick slices. The gold standard was ERCP (n = 40),
      percutaneous cholangiography (n = 1) or surgical findings (n = 9). According to
      this gold standard, 17 patients had bile duct lithiasis and 21 had neoplastic
      obstruction. RESULTS: The sensitivity and specificity of MR cholangiography were
      100% and 94% for the diagnosis of lithiasis obstruction and 95% and 97% for
      neoplastic obstruction. Agreement between the MR cholangiogram and the gold
      standard was good whatever the site of obstruction (range of kappa values: 0.79
      1). CONCLUSION: MR cholangiography with SSFSE sequence is a useful, precise and
      easy to use technique. Acquisition time for thick slices is short (< 2 sec)
      limiting cardiorespiratory artefacts and eliminating the need for post-treatment.

PMID- 9921452
TI  - [Comparison of magnetic resonance angiography with injection of gadolinium and
      conventional arteriography of the ilio-femoral arteries].
AB  - Twenty-three patients underwent conventional arteriography and 3D contrast
      enhanced magnetic resonance angiography explorations. The study was limited to
      the iliofemoral arteries (13 segments for each patient). Each segment was
      classified as having 0-49%, 50-99% or 100% stenosis. Overall results were
      excellent with K = 0.822, sensitivity 92% and specificity 93%. Segment by segment
      analysis corroborated the overall results except for the internal iliac arteries
      and the deep femoral arteries, demonstrating the limitations of this technique in
      this series.

PMID- 9921453
TI  - [Biliary colonic ileus: an unusual cause of colonic obstruction].
AB  - We report a rare case of colonic gallstone obstruction in a patient with
      cholecystocolic fistula. Diagnosis of this condition is usually difficult and
      only achieved at surgery. We review the radiological findings, particularly the
      CT findings, helpful for diagnosis: ectopic gallstone, biliary gas and fistula.
      Early preoperative diagnosis could reduce morbidity and mortality. Treatment is
      surgical with enterolithotomy. There is some controversy over the need to repair
      the fistula.

PMID- 9921454
TI  - [Air in the bone? Diagnosis and treatment of a pneumatocyst of the ilium. Apropos
      of a case].
AB  - We present a case of symptomatic pneumatocyst of the ilium observed in a
      professional scuba diver exposed to pressure variations. Pneumatocysts are rare
      and except for one case reported in a clavicular localization, are always found
      in subchondral bone of the iliac or sacral side of the sacroiliac joint.
      Undoubtedly, air fills an intraosseous node. We report here the first case of
      efficient treatment achieved by filling the cyst via percutaneous access under
      scopic control.

PMID- 9921455
TI  - [Intra-abdominal small round-cell desmoplastic tumor: ultrasonographic and
      computed tomographic aspects. Apropos of a case].
AB  - We report a case of small round-cell desmoplastic tumor located in the abdomen.
      We describe the ultrasound and CT features of this uncommon tumor with poor
      prognosis.

PMID- 9921456
TI  - [What is it? Congenital absence of the left pedicle of C7 vertebra].

PMID- 9921457
TI  - Picture naming of cognate and non-cognate nouns in bilingual aphasia.
AB  - Previous research has found differences in the speed and accuracy of responses
      involving concrete cognate nouns and non-cognate nouns in a range of written and
      "on-line" tasks using neurologically unimpaired, bilingual adults. The present
      study investigated whether cognateness affects verbal confrontation naming
      performance in balanced French/English bilinguals (N = 15 aphasic and 15 non
      aphasic subjects). Subjects met selection criteria for equal proficiency, regular
      use, and early acquisition of both languages. Results of a picture naming test
      show that cognate pictures were more often correctly named in both languages than
      were non-cognates. Some error types and self-correction behaviors also varied
      with cognate status. There were similarities between the results of this study
      and those of previous studies of monolingual naming. Some error types and self
      correction strategies appear to be unique to bilingual speakers. Theoretical
      questions and treatment applications arising from these findings are outlined.

PMID- 9921458
TI  - Visual and verbal metaphors among children with typical language and language
      disorders.
AB  - Twelve children with language disorders and 12 control subjects were presented
      with a series of 24 photographic plates from the Metaphoric Triads Test and asked
      to explain all possible pairings. They also performed a similar task, matched for
      content, using verbally prepared stimuli. For each trial, one pairing had been
      designed to make highly probable a metaphoric pairing. Control subjects provided
      significantly more metaphoric accounts of pairings than children with language
      disorders, regardless of modality. In addition, photographic plates elicited
      significantly more metaphoric pairings than verbal preparations. No significant
      interactions were observed. The findings are discussed from the perspectives of
      (1) generalized symbolic function and (2) verbal mediation function. The authors
      call for more research on the role of verbal mediation in metaphoric reasoning.

PMID- 9921459
TI  - Voice onset time in speech produced by inexperienced signers during simultaneous
      communication.
AB  - This study investigated sentence duration and voice onset time (VOT) of plosive
      consonants in words produced during simultaneous communication (SC) by
      inexperienced signers. Stimulus words embedded in a sentence were produced with
      speech only and produced with SC by 12 inexperienced sign language users during
      the first and last weeks of an introductory sign language course. Results
      indicated significant differences between the speech and SC conditions in
      sentence duration and VOT of initial plosives at both the beginning and the end
      of the class. Voiced/voiceless VOT contrasts were enhanced in SC but followed
      English voicing rules and varied appropriately with place of articulation. These
      results are consistent with previous findings regarding the influence of rate
      changes on the temporal fine structure of speech (Miller, 1987) and were similar
      to the voicing contrast results reported for clear speech by Picheny, Durlach,
      and Braida (1986) and for experienced signers using SC by Schiavetti, Whitehead,
      Metz, Whitehead, and Mignerey (1996).

PMID- 9921460
TI  - Pre- and post-operative counseling for laryngectomees and their spouses: an
      update.
AB  - This survey was developed to determine if pre-operative counseling services have
      improved since the 1978 Keith, Linebaugh, and Cox study. The questions were aimed
      to obtain information on the quality and quantity of support services available
      to laryngectomees and their spouses. Questions addressed the type, amount, and
      content of information received. In addition, questions regarding post-operative
      counseling services for laryngectomees and spouses of laryngectomees also were
      included. Results indicated that 21% of the laryngectomees were not aware that
      laryngectomy surgery would result in loss of voice. In addition, not all speech
      rehabilitation options were explained to the patients. Pre- and post-operative
      counseling services for laryngectomees continue to be inadequate. It appears that
      little change has been made to improve this situation.

PMID- 9921461
TI  - A descriptive study of insight into illness reported by persons with
      schizophrenia.
AB  - 1. Four levels of insight, ranging from lack of insight to complete insight,
      emerged from the interview data and field notes. Insight has many dimensions
      although it has previously been assessed as a unidimensional indicator of
      illness. 2. Persons with schizophrenia differ in insight or ability to recognize
      that they have an illness and the ramifications of the illness. Successful
      participation in rehabilitation requires some degree of insight into the illness.
      3. Consistent family support, medications, and cognitive efforts by the person
      contributed to the developing of insight by the persons interviewed.
      Nevertheless, these conditions were not always sufficient for developing insight.

PMID- 9921462
TI  - The Alumni program: redefining continuity of care in psychiatry.
AB  - The Alumni Program is a novel approach to the continuing care and preventive
      treatment of clients with "chronic" mental illness. This approach demands a
      different conceptualization of outpatient psychiatric intervention. The
      infectious disease model has been deliberately replaced with a chronic illness
      model that more accurately reflects the course and natural history of psychiatric
      illness. The Alumni Program is similar to the approach employed with other
      chronic medical conditions like arthritis, asthma, or diabetes. The program has
      complementary roles for both specialty psychiatric clinicians and family
      practitioners. In addition, the program empowers clients and their families to
      play a key role in their own ongoing adaptation and adjustment to chronic illness
      while striving for optimal wellness.

PMID- 9921463
TI  - Respite care--volunteers as providers.
AB  - 1. Although many studies examine the impact of respite care on caregivers, few
      studies have examined the impact of such programs on the volunteer respite
      provider. Results of such formative evaluation studies must be antecedent to the
      question of whether respite care "works." 2. Fear of persons with Alzheimer's
      Disease (AD) was a consistent theme verbalized in this study. Educational
      programs must therefore include more exposure to actual persons with AD. 3.
      Caregivers with some past experience composed the majority of volunteers in this
      group (n = 78%). Recruiting former caregivers of deceased persons with AD may be
      fruitful future areas of study.

PMID- 9921464
TI  - A review of third-party reimbursement issues for advanced practice nurses.
AB  - 1. Dramatic increase in health care costs are attributed to a previously
      unlimited reimbursement structure for health care organizations and physicians,
      coupled with a focus on acute, high-technologic, and tertiary care. 2. Advanced
      practice nurses (APNs) have demonstrated the ability to positively affect patient
      outcomes through the provision of high quality, accessible, and cost-effective
      care. 3. The nursing profession has continued to endure a disproportionate
      struggle to gain third-party reimbursement. APNs must educate the public about
      their role and continue lobbying for legislation that mandates third-party
      reimbursement.

PMID- 9921465
TI  - Mycobacteria. Bugs and bugbears.

PMID- 9921466
TI  - Mycobacteria. General culture methodology and safety considerations.

PMID- 9921467
TI  - Isolation of genomic DNA from mycobacteria.

PMID- 9921468
TI  - Nucleic-acid extraction: plasmid/cosmid DNA.

PMID- 9921469
TI  - Pulsed field gel electrophoresis for mycobacteria.

PMID- 9921470
TI  - Extraction of RNA from mycobacteria.

PMID- 9921471
TI  - Preparation of cell-free extracts from mycobacteria.

PMID- 9921473
TI  - Using MycDB on the World-Wide Web.

PMID- 9921472
TI  - Preparation of cell-wall fractions from mycobacteria.

PMID- 9921474
TI  - Conjugating DNA into mycobacteria.

PMID- 9921475
TI  - Electroporation of mycobacteria.

PMID- 9921476
TI  - Mycobacteriophages.

PMID- 9921477
TI  - Chemical mutagenesis of mycobacteria.

PMID- 9921478
TI  - Tn611 transposon mutagenesis in Mycobacterium smegmatis using a temperature
      sensitive delivery system.

PMID- 9921479
TI  - Homologous recombination in Mycobacterium smegmatis. Screening methods for
      detection of gene replacement.

PMID- 9921480
TI  - Gene replacement in Mycobacterium smegmatis using a dominant negative selectable
      marker.

PMID- 9921481
TI  - Gene replacement in Mycobacterium intracellulare.

PMID- 9921482
TI  - Gene replacement in Mycobacterium bovis BCG.

PMID- 9921483
TI  - The application of bacterial luciferase as a reporter gene in mycobacteria.

PMID- 9921484
TI  - Green fluorescent protein. A tool for gene expression and cell biology in
      mycobacteria.

PMID- 9921485
TI  - Expression of genes in mycobacteria.

PMID- 9921486
TI  - Secretion of mammalian proteins from mycobacteria.

PMID- 9921487
TI  - Intracellular gene expression. Analysis of RNA from mycobacteria in macrophages
      using RT-PCR.

PMID- 9921488
TI  - Analysis of mycobacterial differential gene expression by RAP-PCR.

PMID- 9921489
TI  - Mycobacterial speciation.

PMID- 9921490
TI  - Species identification of mycobacteria using rDNA sequencing.

PMID- 9921491
TI  - Detection of Mycobacterium tuberculosis by a colorimetric polymerase chain
      reaction.

PMID- 9921492
TI  - Rapid detection and simultaneous strain differentiation of Mycobacterium
      tuberculosis complex bacteria by spoligotyping.

PMID- 9921493
TI  - Computer analysis of IS6110 RFLP patterns of Mycobacterium tuberculosis.

PMID- 9921494
TI  - Detection of mutations in mycobacteria by PCR-SSCP (single-strand conformation
      polymorphism).

PMID- 9921495
TI  - The use of luciferase-reporter phage for antibiotic-susceptibility testing of
      mycobacteria.

PMID- 9921496
TI  - Overview of ligand-receptor binding techniques.

PMID- 9921497
TI  - [3H]-GABA binding to GABAA and GABAB sites on rat brain crude synaptic membranes.

PMID- 9921498
TI  - Characterization of imidazoline receptors by radioligand binding.

PMID- 9921499
TI  - Radioligand binding to solubilized 5-HT3 receptors.

PMID- 9921500
TI  - Solubilized muscarinic acetylcholine receptors from the rat myocardium:
      pharmacological and hydrodynamic characterization.

PMID- 9921501
TI  - Radioligand binding in intact cells.

PMID- 9921502
TI  - Autoradiography of peptide receptors.

PMID- 9921503
TI  - Measurement of brain GABA-benzodiazepine receptor levels in vivo using emission
      tomography.

PMID- 9921504
TI  - Analysis of binding data.

PMID- 9921505
TI  - Definition of receptors in radioligand-binding experiments.

PMID- 9921506
TI  - Autoradiography of enzymes, second messenger systems, and ion channels.

PMID- 9921507
TI  - Whole human brain autoradiography of serotonin re-uptake inhibitors.

PMID- 9921508
TI  - Measurement of agonist-stimulated [35S]GTP gamma S binding to cell membranes.

PMID- 9921509
TI  - mRNA: detection by in Situ and northern hybridization.

PMID- 9921510
TI  - Free radical and antioxidant protocols. Introduction.

PMID- 9921511
TI  - Oxygen consumption methods. Xanthine oxidase and lipoxygenase.

PMID- 9921512
TI  - Spin trapping and electron paramagnetic resonance spectroscopy.

PMID- 9921513
TI  - In vivo detection of free radicals in real time by low-frequency electron
      paramagnetic resonance spectroscopy.

PMID- 9921514
TI  - Single photon counting.

PMID- 9921515
TI  - Measurement of reactive oxygen species in whole blood and mononuclear cells using
      chemiluminescence.

PMID- 9921516
TI  - Assay of phospholipid hydroperoxides by chemiluminescence-based high-performance
      liquid chromatography.

PMID- 9921517
TI  - Sensitive and specific fluorescent probing of oxidative stress in different
      classes of membrane phospholipids in live cells using metabolically integrated
      cis-parinaric acid.

PMID- 9921518
TI  - Aromatic hydroxylation. Salicylic acid as a probe for measuring hydroxyl radical
      production.

PMID- 9921519
TI  - Simple assay for the level of total lipid peroxides in serum or plasma.

PMID- 9921520
TI  - Simple procedure for specific assay of lipid hydroperoxides in serum or plasma.

PMID- 9921521
TI  - Antibodies against malondialdehyde-modified proteins. Induction and ELISA
      measurement of specific antibodies.

PMID- 9921522
TI  - Oxidized LDL and Lp(a). Preparation, modification, and analysis.

PMID- 9921523
TI  - Oxidized and unoxidized fatty acyl esters.

PMID- 9921524
TI  - Synthesis of lipid and cholesterol hydroperoxide standards.

PMID- 9921525
TI  - Separation of hydroxy and hydroperoxy polyunsaturated fatty acids by high
      pressure liquid chromatography.

PMID- 9921526
TI  - Products of creatinine with hydroxyl radical as a useful marker of oxidative
      stress in vivo.

PMID- 9921528
TI  - Electrochemical detection of 8-hydroxy-2-deoxyguanosine levels in cellular DNA.

PMID- 9921527
TI  - Quantitative analysis of peptide and protein changes in ischemic hippocampal
      tissue by HPLC.

PMID- 9921529
TI  - Nitric oxide synthase.

PMID- 9921530
TI  - Quantitation of heme oxygenase (HO-1) copies in human tissues by competitive
      RT/PCR.

PMID- 9921531
TI  - A fluorescent-based assay for measurement of phospholipase A2 activity. A facile
      assay for cell sonicates.

PMID- 9921532
TI  - Autofluorescent ceroid/lipofuscin.

PMID- 9921533
TI  - In vivo technique for autofluorescent lipopigments.

PMID- 9921534
TI  - An ex vivo erythrocyte model for investigating oxidative metabolism.

PMID- 9921535
TI  - Purification of vesicular carriers from rat hepatocytes by magnetic
      immunoadsorption.

PMID- 9921536
TI  - Simultaneous determination of serum retinol, tocopherols, and carotenoids by
      HPLC.

PMID- 9921537
TI  - EPR measurements of nitric oxide-induced chromanoxyl radicals of vitamin E.
      Interactions with vitamin C.

PMID- 9921538
TI  - Nonvitamin plasma antioxidants.

PMID- 9921539
TI  - Regulatory antioxidant enzymes.

PMID- 9921540
TI  - In vitro screening for antioxidant activity.

PMID- 9921541
TI  - Antioxidant activity of low-density lipoprotein.

PMID- 9921542
TI  - Lipoic acid as an antioxidant. The role of dihydrolipoamide dehydrogenase.

PMID- 9921543
TI  - Reduced glutathione and glutathione disulfide.

PMID- 9921544
TI  - Analysis of coenzyme Q10 content in human plasma and other biological samples.

PMID- 9921545
TI  - A simple luminescence method for detecting lipid peroxidation and antioxidant
      activity in vitro.

PMID- 9921546
TI  - Analysis of oxidation and antioxidants using microtiter plates.

PMID- 9921547
TI  - Trace element analysis of biological samples by analytical atomic spectroscopy.

PMID- 9921548
TI  - Energy dispersive X-ray microanalysis.

PMID- 9921549
TI  - Pro-oxidant and antioxidant effects of estrogens.

PMID- 9921550
TI  - Artificial radical generating and scavenging systems. Photo-Fenton reagent and
      caged compounds.

PMID- 9921551
TI  - Normal pelvic floor anatomy.
AB  - The anatomy of the pelvic floor includes structures responsible for active and
      passive support of the urethrovesical junction, vagina, and anorectum. Intrinsic
      and extrinsic properties of the urethrovesical neck and anorectum allow
      maintenance of urinary and anal continence at rest and with activity. Damage to
      these structures may lead to loss of support and loss of normal function of the
      urethra, bladder, and anorectum. Over time, this damage can result in isolated or
      combined pelvic organ prolapse, urinary incontinence, and anal incontinence.

PMID- 9921552
TI  - Normal pelvic floor physiology.
AB  - This article outlines the normal physiology of the female pelvic floor, including
      normal urinary storage and voiding, normal colorectal storage, and defecation.
      Physiologic changes during a woman's lifetime that may affect bladder and bowel
      function are also considered. An important framework for understanding the normal
      physiology of the female pelvic floor is provided, so the reader may gain a more
      thoughtful approach to the recognition and treatment of pelvic floor
      pathophysiology.

PMID- 9921553
TI  - Epidemiology and natural history of pelvic floor dysfunction.
AB  - Pelvic floor dysfunction, including urinary incontinence, anal incontinence, and
      pelvic organ prolapse, is extremely common, affecting at least one-third of adult
      women. A minority of patients sustaining these conditions volunteer their
      symptoms. Risk factor identification and the development of tactics for
      prevention are significant priorities for future research. Understanding both the
      specific predisposing factors that place an individual woman at risk and the
      precise events of the labor and delivery process that initiate injury and
      dysfunction is important for primary prevention. Defining the relative importance
      of various promoting and decompensating factors is essential for secondary
      prevention.

PMID- 9921554
TI  - Pathophysiology of female lower urinary tract dysfunction.
AB  - Urinary incontinence is a disorder with widely varying severity, patient
      symptoms, and etiologies. Urine loss can be because of reversible or irreversible
      systemic disease, abnormalities of urine storage, or voiding phase disorders. The
      optimal work up of an individual incontinence may include evaluation of
      neurologic, muscular, and urogenital systems, as well as medical, pharmaceutical,
      environmental, and psychosocial issues.

PMID- 9921555
TI  - Pathophysiology of pelvic organ prolapse.
AB  - Pelvic organ prolapse is usually caused by weakness of the pelvic diaphragm.
      Descent of the pelvic diaphragm places stress on the endopelvic connective tissue
      support system. Subsequent increases in intra-abdominal pressure result in
      prolapse. In the majority of cases, labor and childbirth are thought to be the
      primary factors responsible for pelvic neuropathies and tissue damage that
      predispose to the development of POP. Certain connective tissue defects,
      congenital defects, and operative procedures also contribute to pelvic support
      defects.

PMID- 9921556
TI  - Pathophysiology of anorectal dysfunction.
AB  - Anorectal disorders are the cause of significant discomfort and embarrassment in
      women. The onset typically follows childbirth and symptoms increase with age.
      Anal incontinence, rectovaginal fistula, rectal prolapse, anal fissure, and
      constipation are considered.

PMID- 9921557
TI  - The clinical evaluation of pelvic floor dysfunction.
AB  - Although Baden concluded that "the pelvic exam is just the pelvic exam," the
      history and examination are tools of no less merit than the cystometrogram or
      scalpel for clinicians treating patients with symptomatic pelvic floor
      dysfunction. An effective history and physical examination provide the basis for
      effective management of the patient's symptoms.

PMID- 9921558
TI  - Physiologic evaluation of the pelvic floor.
AB  - This article has addressed the value, technique, rationale, and limitations of
      the commonly performed physiologic tests of the pelvic floor. Urodynamics
      provides a means for evaluation of the lower urinary tract and for assessment of
      the filling and emptying phases of the bladder. Neurophysiologic tests including
      EMG and nerve conduction studies offer methods to assess the neuromuscular
      integrity of the urethral and anal sphincteric mechanisms and the pelvic floor.
      Anorectal manometry studies provide a means of measuring pressure in the rectum
      and anal canal, rectal compliance, and anorectal reflexes and sensation in
      patients with anal incontinence and select patients with constipation. Colonic
      transit studies permit an assessment of functional constipation and may be
      helpful in the evaluation of patients in whom standard management of constipation
      has failed. Any test used in the evaluation of patients with pelvic floor
      dysfunction should be validated and found to be reliable. Most patients in need
      of complex physiologic evaluation are identified on the basis of their history
      and physical examination findings.

PMID- 9921559
TI  - Imaging studies of the pelvic floor.
AB  - A variety of imaging modalities complement the history and physical examination
      in the investigation of pelvic floor dysfunction in women. Current fluoroscopic
      techniques, including defocography, can reveal underlying pelvic floor defects by
      reproducing normal daily activities that cause symptoms. Magnetic resonance
      imaging provides fine musculoskeletal detail of this region in anatomic plane not
      well seen via computerized tomography. Ultrasound is used primarily in assessment
      of the anal sphincter muscles. Cystourethroscopy provides direct visualization of
      the lower urinary tract. This article describes the clinical applications and
      technique of each modality.

PMID- 9921560
TI  - Nonsurgical management of pelvic floor dysfunction.
AB  - In the 50 years since pelvic muscle exercises were introduced for the nonsurgical
      management of pelvic floor dysfunction related to parturition, a variety of
      approaches have been introduced and the scope of indications has grown. This
      article describes the evaluation of patients with pelvic floor complaints,
      discusses additional techniques for performing pelvic muscle exercises including
      biofeedback and electrical stimulation, details a comprehensive educational
      program, and examines the literature on the use of pelvic muscle exercises for
      the treatment of stress and urge urinary incontinence.

PMID- 9921561
TI  - Pharmacologic management of pelvic floor dysfunction.
AB  - Pharmacologic therapy is an important part of the treatment armamentarium for
      urogynecologic disorders. Current and future research will determine the utility
      of such therapy as medications with fewer side effects and more targeted efficacy
      are developed.

PMID- 9921562
TI  - Surgical management of urinary incontinence.
AB  - Surgery for stress incontinence is selected according to specific problems in
      each patient. Patients with ISD can be identified and selected for sling surgery
      or collagen injection therapy. Other patients may be managed successfully by
      retropubic urethropexy, either open or laparoscopic. Diagnostic evaluation should
      be thoughtful and extensive, with good correlation of findings and presenting
      symptoms to apply therapy in a specific manner to each patient.

PMID- 9921563
TI  - Management of pelvic organ prolapse.
AB  - The wide variety of available pessaries permits rather precise choice of pessary
      to meet a given patient's needs. Different approaches are reviewed. A paradigm
      for choosing a surgical repair based on the fascial and muscular support defects,
      as well as the functional demands and limitations of the patient is presented.

PMID- 9921564
TI  - Management of colorectal-anal dysfunction.
AB  - Although the majority of patients with low-grade anal incontinence and
      constipation should be treated medically, for some, efforts will be unsuccessful
      and surgical therapy will be in order. Full thickness rectal prolapse will, in
      all early cases, be treated surgically. This article outlines the surgical
      treatment options for patients with anal incontinence, rectal prolapse, and
      constipation. Optimal functional outcomes with surgical treatment are based on
      full physiologic evaluation and careful patient selection.

PMID- 9921565
TI  - Nurses have a responsibility to learn more about end-of-life care.

PMID- 9921566
TI  - The effect of an educational intervention on decreasing pain intensity in elderly
      people with cancer.
AB  - PURPOSE/OBJECTIVES: To determine if an educational intervention related to pain
      management could decrease pain intensity in elderly people with cancer. DESIGN:
      Quasi-experimental pretest/post-test design. SETTING: A private oncology practice
      in urban west central Florida. SAMPLE: 36 subjects who were 65 years of age or
      older and had a known cancer diagnosis. METHODS: Visual Analog Scale (VAS)
      completed by each subject. Subjects were randomized to an experimental or a
      control group. Experimental group members watched a 14-minute video produced by
      the investigator that presented information contained in the booklet "Managing
      Cancer Pain." Experimental group members also received a copy of the booklet.
      Control group members received pain management instructions from the office
      staff. Two weeks later, subjects completed the VAS at two different times on that
      day and mailed them to the investigator. FINDINGS: Analysis of covariance
      revealed a statistically significant difference in pain intensity between the
      control group and the experimental group. CONCLUSIONS: Pain management in elderly
      people with cancer has been underrepresented in the literature and minimally
      studied. This study indicated that an educational intervention aimed at elderly
      people with cancer was effective and implies that educational interventions
      should be a central component in prevention and management of cancer pain in the
      elderly. IMPLICATIONS FOR NURSING PRACTICE: Every effort should be made to
      educate elderly people with cancer on prevention and management of pain. Nurses
      must take a leading role in identifying and implementing educational strategies
      for cancer pain management and side effect control for their elderly patients.

PMID- 9921567
TI  - Fatigue in 7- to 12-year-old patients with cancer from the staff perspective: an
      exploratory study.
AB  - PURPOSE/OBJECTIVES: To document and analyze the perspectives of staff members who
      provide direct care to 7- to 12-year-old patients with cancer regarding the
      nature and characteristics of fatigue, causes of fatigue, and effective
      interventions for this population of young patients. DESIGN: Exploratory.
      SETTINGS: A pediatric oncology unit at a children's hospital in the southwest and
      a pediatric research center for childhood catastrophic diseases in the mid-south.
      SAMPLE: A convenience sample of 38 staff members (8 advanced practice nurses, 23
      staff nurses, 2 nurses managers, 3 nutritionists, 1 chaplain, and 1 physician)
      whose experience in pediatric oncology ranged from two months to 23 years.
      METHODS: Nine open-ended questions were posed to staff members during focus group
      sessions. Staff responses were analyzed using content analysis techniques and the
      Wilson concept analysis technique. MAIN RESEARCH VARIABLE: Staff perceptions of
      fatigue in 7- to 12-year-old patients with cancer. FINDINGS: Fatigue is a state
      of diminished to complete loss of energy or will that is influenced by
      environmental, biochemical, personal, cultural, and treatment-related factors.
      This state, which may be acute, episodic, or chronic, can be accompanied by a
      changing emotional or mental state. CONCLUSIONS: Staff perceive fatigue to be a
      debilitating symptom for these children. When attempting to determine the
      presence or absence of fatigue, staff primarily compare a child's current state
      with his or her previous state rather than that of other children. Staff see
      themselves as having a role in causing and alleviating fatigue in this patient
      group. IMPLICATIONS FOR NURSING PRACTICE: Staff can use these findings to help
      them identify the presence of fatigue in these children and to identify
      contributing and alleviating factors.

PMID- 9921568
TI  - Past and present herbs used to treat cancer: medicine, magic, or poison?
AB  - PURPOSE/OBJECTIVES: To provide an overview of the past and present use of herbs,
      thereby dispelling the belief that herbs are secret cancer remedies unknown to or
      ignored by the biomedical community. DATA SOURCES: Historical and current
      pharmacy, medical, and nursing literature. DATA SYNTHESIS: More than 3,000
      species of herbs used in treating cancer since 2838 BC are known to biomedicine,
      yet popular lay literature persists in perpetrating the myth that medicine has
      ignored the potential uses of herbs. Secrecy about herbs has been fashionable
      since the Middle Ages. Magical and virtuous herbs, named in a book of secrets
      from that age, are examined for their historical and current use in cancer
      treatment. Popular unproven herbs, as well as proven herbs used in chemotherapy,
      also are discussed. CONCLUSIONS: Greater accessibility to information about the
      use of herbs historically, popularly, and currently would help dispel the
      secrecy, giving healthcare professionals and patients and opportunity to make
      informed choices. IMPLICATIONS FOR NURSING PRACTICE: Nurses with knowledge of
      herbs can be valuable resources to patients and professional colleagues. Members
      of the professional community (nurses, doctors, pharmacists, and social workers)
      need to take collegial responsibility in informing each other and their patients
      about herbs, including their potential risks, possible benefits, and antidotes
      for overdose.

PMID- 9921570
TI  - An undergraduate oncology nursing course.
AB  - PURPOSE/OBJECTIVES: To develop an undergraduate oncology nursing course that
      provides deeper, more structured education in cancer care. DATA SOURCES: Oncology
      Nursing Society and American Cancer Society materials, current oncology nursing
      texts, and published periodical literature. DATA SYNTHESIS: An undergraduate
      oncology nursing course was designed and successfully conducted that included
      clinical experience in the inpatient, outpatient, and home environments with
      experience in dealing with as many aspects of patient care as possible.
      CONCLUSIONS: An oncology nursing course taught by expert practitioners and
      mentors can and should be offered annually to undergraduate nursing students.
      IMPLICATIONS FOR NURSING PRACTICE: Improved oncology patient care should result
      when nurses caring for patients with cancer receive specific information and
      specialized clinical experience as students that they can apply upon program
      completion as healthcare providers in the community.

PMID- 9921569
TI  - The effects of guided imagery on comfort of women with early stage breast cancer
      undergoing radiation therapy.
AB  - PURPOSE/OBJECTIVES: To measure the effectiveness of customized guided imagery for
      increasing comfort in women with early stage breast cancer. DESIGN: Experimental
      longitudinal, random assignment to groups. SETTING: Two urban radiation oncology
      departments. SAMPLE: 53 women (26 in the experimental group, 27 in the control
      group) aged 37-81; 80% European and 10% African American with stage I or II
      breast cancer about to begin radiation therapy. METHODS: The experimental group
      was to listen to a guided imagery audiotape once a day for the duration of the
      study. The Radiation Therapy Comfort Questionnaire was self-administered at three
      time points: prior to the introduction of intervention and the beginning of
      radiation therapy (Time 1), three weeks later (Time 2), and three weeks after
      completing radiation therapy (Time 3). The State Anxiety Inventory was
      administered at Time 1 only. MAIN RESEARCH VARIABLES: The effect of use of guided
      imagery on comfort with anxiety as a control variable. FINDINGS: Pooled data
      indicated a significant overall increase in differences in comfort between the
      treatment and control group, with the treatment group having higher comfort over
      time. The data also revealed a significant linear trend in differences between
      groups. No significant interaction of group and time existed. CONCLUSIONS: Guided
      imagery is an effective intervention for enhancing comfort of women undergoing
      radiation therapy for early stage breast cancer. The intervention was especially
      salient in the first three weeks of therapy. IMPLICATIONS FOR NURSING PRACTICE:
      Guided imagery audiotapes specifically designed for this population were resource
      effective in terms of cost, personnel, and time.

PMID- 9921571
TI  - Effect of subcutaneous granulocyte colony-stimulating factor injectate volume on
      drug efficacy, site complications, and client comfort.
AB  - PURPOSE/OBJECTIVES: To determine the effect of administering 1.6 ml (480 mcg) of
      granulocyte colony-stimulating factor (G-CSF) in one subcutaneous injection or
      two injections of 0.8 ml each. DESIGN: Experimental. SETTING: 27-bed bone marrow
      transplant intensive care unit of a metropolitan, university medical center in
      the southwestern United States. SAMPLE: Nonprobability; 76 women who received
      high-dose chemotherapy for breast cancer followed by hemopoietic rescue. METHODS:
      Subjects were randomized into an experimental group that received one injection
      per 480 mcg dose and a control group that received two injections per 480 mcg
      dose administered by research associates using a standardized injection
      technique. MAIN RESEARCH VARIABLES: Injectate volume. The number of days post
      transplant until the absolute neutrophil count (ANC) returned to 1,000/mm3, the
      incidence and surface area in mm2 of site complications, and scores on Tursky's
      Quantified Pain Descriptor immediately following the injection(s). FINDINGS: No
      significant difference existed between the two groups in ANC recovery time,
      frequency or size of site complications, or intensity, reaction, or sensation of
      discomfort reported. CONCLUSIONS: Administering 1.6 ml doses of G-CSF in one
      injection instead of two does not result in slower ANC recovery, induration, more
      frequent or larger bruises or areas of erythema, or greater client discomfort.
      IMPLICATIONS FOR NURSING PRACTICE: Administering one injection instead of two may
      decrease patients' anxiety, the nursing time needed for preparation and
      administration of injections, patient instruction for self-administration, the
      potential for contamination of vials or loss of dose, and the cost of supplies.

PMID- 9921572
TI  - The impact of primary and modular nursing delivery systems on perceptions of
      caring behavior.
AB  - PURPOSE/OBJECTIVES: To determine if differences existed in patients' and family
      members' perceptions of caring behaviors after the transition from a primary to a
      modular care delivery system. DESIGN: Descriptive, comparative, and
      correlational. SETTING: Urban, inpatient, acute-care hospital. SAMPLE: A
      convenience sample of 42 patients with cancer hospitalized for chemotherapy
      administration or complications arising from their diagnoses and 27 of their
      family members. Ninety-four data sets were collected--62 from the patients and 32
      from the family members. METHODS: Subjects were asked to evaluate their nurse's
      caring attributes using the Caring Perception index. Caring scores of patients
      receiving primary nursing care were compared to caring scores of patients
      receiving modular nursing care. MAIN RESEARCH VARIABLE: Patients' and family
      members' perception of caring. FINDINGS: Mean caring scores did not differ
      significantly between patients receiving primary care (mean = 35.9, SD = 5.4) and
      patients receiving modular care (mean = 36.2, SD = 5.3). Patient and nursing
      delivery characteristics were used to predict and explain variance in the
      dependent variable care. Number of days hospitalized accounted for 14% of the
      variance, with those patients hospitalized longer rating nurses as more caring.
      CONCLUSIONS: The longer a patient stays in the hospital, the greater the
      likelihood the patient and family members will feel nurses exceeded exceptions
      for caring. The findings support other studies that have compared quality care
      indicators across different types of delivery systems. IMPLICATIONS FOR NURSING
      PRACTICE: Measures to evaluate quality care should be used when transitioning to
      new delivery models. Nurses need to recognize that not all patients value the
      same nurse qualities equally. When receiving care over an extended period of time
      from same nurse, patients and family members are more likely to rate the nurse as
      exceeding expectations.

PMID- 9921573
TI  - Quality-of-life evaluation in patients receiving treatment for advanced prostate
      cancer.
AB  - PURPOSE/OBJECTIVES: To evaluate the quality-of-life (QOL) experience in patients
      who are receiving treatment for advanced prostate cancer and the relationship
      between response to that treatment and QOL. DESIGN: Descriptive comparative
      study, repeated measures. SETTING: Medical oncology clinic in a comprehensive
      cancer center. SAMPLE: 33 patients receiving treatment for advanced prostate
      cancer. METHODS: Patient self-administered questionnaires and chart review. MAIN
      RESEARCH VARIABLES: Response to therapy and QOL. FINDINGS: No significant
      differences were seen in patients at the baseline evaluation. Patients who
      demonstrated response to therapy based on declining prostate specific antigen
      levels, however, demonstrated a significant increase in their QOL scores compared
      to those patients who were not responding to treatment. CONCLUSIONS: Although
      significant differences in survival at this stage of prostate cancer in patients
      who receive therapeutic treatment versus those who do not have yet to be
      demonstrated, there appears to be a benefit in QOL for those patients who respond
      to therapy. IMPLICATIONS FOR NURSING PRACTICE: These data support the use of QOL
      measurements in patients undergoing treatment for advanced prostate cancer. This
      information can be used in discussions with patients who are facing treatment
      decisions and who are concerned about the impact of treatment on their overall
      QOL. The data also stimulate questions for future research on QOL in this
      population, such as the difference in QOL in those patients who choose
      therapeutic treatment versus those who do not.

PMID- 9921574
TI  - Families' awareness of and response to dying.
AB  - PURPOSE/OBJECTIVES: To explore how family care-givers develop and respond to an
      awareness that their relative is dying. DESIGN: Qualitative, interpretive.
      SETTINGS: Four major providers of cancer services in Brisbane, Australia,
      including a hospital, hospice, homecare nursing service, and oncologist's office.
      SAMPLE: 20 recently bereaved adult family caregivers (mean age = 48.5): 11
      females, 9 males--16 spouses, 2 daughters, and 2 mothers of adults. METHODS:
      Semistructured interviews transcribed verbatim and content analyzed. MAIN
      RESEARCH VARIABLE: Developing and responding to an awareness of dying. FINDINGS:
      Five major themes emerged from the analysis. Two core categories, Being Uncertain
      and Agonizing, depict the emotional struggles that characterize the process of
      developing an awareness of dying. Three additional categories-Hoping, Pretending,
      and Preparing-represent strategies used by family caregivers to manage these
      emotional struggles. CONCLUSIONS: Developing an awareness of dying is a gradual
      process for family caregivers. Uncertainty and anguish characterize this process.
      Several factors contribute to this uncertainty and agony, including interactions
      with healthcare providers. Family caregivers attempt to manage this developing
      awareness by hoping, pretending, and preparing for death. IMPLICATIONS FOR
      NURSING PRACTICE: Nurses need to identify processes to ensure that family
      caregivers' needs for information and support are given high priority and that
      supportive interventions identified are based on a sensitive understanding of the
      experience of the family caregiver. The processes may include assisting family
      caregivers to maintain hope, sustain social relationships, and make preparations
      for the death. Further research into how family caregivers use these strategies
      for managing their developing awareness of dying is required.

PMID- 9921575
TI  - A chemotherapy standard order form: preventing errors.
AB  - PURPOSE/OBJECTIVES: To describe the development and implementation of one
      approach to standardize and document chemotherapy orders for patients in the
      acute-care setting. DATA SOURCES: Multidisciplinary team, Oncology Nursing
      Society standards of care, clinical experience, and published literature. DATA
      SYNTHESIS: To avoid errors in ordering, dispensing, and administering
      chemotherapy that may have the potential for serious adverse patient outcomes, a
      standardized order sheet was developed to consistently document information
      regarding chemotherapy ordering and administration throughout the hospital. Each
      component of the form is essential in promoting safety and efficiency in the
      chemotherapy ordering and administration process. CONCLUSION: A standardized
      approach dramatically improved ordering, dispensing, and administering
      chemotherapy. Multidisciplinary verification and documentation of dose and
      schedule helps reduce chemotherapy-related errors. IMPLICATIONS FOR NURSING
      PRACTICE: The chemotherapy order sheet saves time and is comprehensive and
      consistent. Use of the order sheet also has increased interdisciplinary
      collaboration and assisted all members of the team in documenting required
      information.

PMID- 9921576
TI  - Orientation of the peptidoglycan chains in the sacculus of Escherichia coli.
AB  - The organization of chains of oligopeptidoglycan in the saccular wall is of
      critical importance in the study of the mechanism and physiology of prokaryotic
      wall growth. The electron microphotographs of De Pedro et al. present new
      findings and can be used to negate or at least raise questions about the
      previously accepted conclusion that the glycan chains are oriented transversely
      to the axis of rod-shaped Escherichia coli. This suggests caution in assuming
      that the glycan chains in the murein structure are parallel to each other and are
      perpendicular to the axis of the cell. These results should reopen the question
      of not only the orientation of the peptidoglycan chains, but the possibility of
      variability in orientation. Three classes of hypotheses about wall growth are
      reconsidered and problems with them are presented. The new results from De
      Pedro's laboratory and the experimental glycan chain length distribution argue
      against proposed systematic models. These include models that postulate belts or
      hoops stretched around the circumference of the cell and mechanisms that insert
      new chains of the length of presumptive "docking" strands in the stress-bearing
      wall. They are consistent, however, with the surface stress theory that proposes
      that random enzyme action together with physical forces are involved in the
      elongation of the rod-shaped Gram-negative wall.

PMID- 9921577
TI  - Sequence comparison of outer membrane phospholipases A: implications for
      structure and for the catalytic mechanism.
AB  - In this study, the nucleotide sequence of the Enterobacter agglomerans pldA gene
      encoding outer membrane phospholipase A (OMPLA; EC 3.1.1.32) was determined. Five
      other OMPLA amino acid sequences have previously been described, and screening of
      data bases of whole genome sequencing projects revealed the presence of proteins
      with homology to OMPLA in Helicobacter pylori, Campylobacter jejuni, Yersinia
      pestis, Neisseria menigitidis and Neisseria gonorrhoeae. Comparison of these
      eleven OMPLA amino acid sequences revealed that 30 amino acid residues are
      completely conserved. Implications of the sequence comparison for the catalytic
      mechanism of OMPLA are discussed. The presence of proteins homologous to OMPLA
      even in non-enterobacterial Gram-negative bacteria indicates an important
      physiological role of this enzyme.

PMID- 9921578
TI  - Genotypic characterization of thermophilic bacilli: a study on new soil isolates
      and several reference strains.
AB  - A genotypic study using amplified ribosomal DNA restriction analysis (ARDRA),
      random amplified polymorphic DNA fingerprinting (RAPD) and ribosomal spacer
      analysis (RSA) in comparison with DNA-DNA reassociation experiments was carried
      out with 85 thermophilic Bacillus isolates from uncultivated soil of 14 different
      geographical areas and seventeen reference strains representing defined
      thermophilic Bacillus species. This approach permitted the attribution of 51% of
      the new isolates to the Bacillus thermoleovorans group and the identification of
      40% of the new isolates as B. "thermodenitrificans". Moreover, 2 strains were
      assigned to B. pallidus species and 1 isolate to B. thermosphaericus species. The
      remaining 6% of our thermophilic isolates from soil, constituting 2 DNA-DNA
      homology groups, are still unidentified. A detailed genotypic characterization of
      the heterogeneous species of B. thermoleovorans and B. stearothermophilus was
      also presented.

PMID- 9921579
TI  - A putative adhesin gene cloned from Campylobacter jejuni.
AB  - Thirteen Campylobacter jejuni strains of human origin showed differing behaviours
      when analysed for their ability to bind the Caco-2 cell line in vitro, suggesting
      variations in genetic complements and/or regulation. We designed an
      oligonucleotide probe corresponding to a highly conserved part of adhesins from
      various Gram-negative bacteria. Among our laboratory collection, Southern
      hybridization has demonstrated that only a discrete number of strains harbour
      this sequence. The corresponding gene has been cloned from our prototype strain
      and sequence analysis has confirmed homology with Gram-negative bacterial
      adhesins. The ORF corresponded to 869 amino acids; we named this protein P95.
      Protein sequence similarity assessment demonstrated that this gene product
      belongs to the family of proteins including the filamentous haemagglutinin of
      Bordetella pertussis and the high-molecular-weight surface-exposed adhesins of
      Haemophilus influenzae. Comparison of adhesion and hybridization results
      emphasized the involvement of this gene in an essential pathogenic process of
      Campylobacter.

PMID- 9921580
TI  - AFLP allows the identification of genomic markers of ruminant Chlamydia psittaci
      strains useful for typing and epidemiological studies.
AB  - Amplified fragment length polymorphism (AFLP), a novel method for molecular
      typing, was evaluated for its ability to differentiate among a group of highly
      related Chlamydia psittaci strains isolated from ruminants and belonging to
      serotype 1. A total set of 12 strains were included in this study, 10 strains
      inducing abortion in ruminants and 2 strains from faecal samples. For the AFLP
      analysis, the total purified genomic DNA of each strain was submitted to a one
      step digestion-ligation reaction for 3 h at 37 degrees C. DNA was digested with a
      single restriction endonuclease Mspl and ligated to specially constructed
      adapters. Subsequently, restricted fragments were selectively amplified under
      high stringency PCR conditions using primers complementary to the adapters.
      Amplified products were then resolved on agarose gel electrophoresis. The method
      is easy to perform, fast and reproducible. AFLP enabled characterization of C.
      psittaci strains at the infra-subspecific level. Thus, AFLP led to the
      identification of a cluster of strains on the basis of their AFLP patterns,
      constituted by French chlamydial isolates. It also permitted differentiation
      among strains in relation to host origin and to clinical syndromes. These data
      confirmed the highly discriminative power of AFLP towards the differentiation of
      closely related ruminant C. psittaci strains. The analysis will need to be
      applied to more samples to check the usefulness of AFLP markers in
      epidemiological and evolutionary studies.

PMID- 9921581
TI  - Molecular characterization of Vibrio cholerae O1 strains isolated in Romania.
AB  - A collection of 89 Vibrio cholerae O1 strains, isolated in Romania between 1977
      and 1994, and 6 strains from the Republic of Moldavia, was characterized by
      ribotyping, toxin gene restriction pattern (toxinogenotype) and distribution of
      cholera toxin gene (ctx), accessory toxin gene (ace) and zonula occludens toxin
      gene (zot). After Bg/I endonuclease restriction of chromosomal DNA, a total of 18
      ribotypes and 21 toxinogenotypes were distinguished. Deletions in the core region
      of the toxin gene cassette were found in 20% of strains; however, with the
      exception of one strain, all the isolates contained the ctx gene. Used in
      association, the three methods of molecular typing provided an accurate
      characterization of V. cholerae O1 isolates.

PMID- 9921583
TI  - Human growth hormone transgene expression increases the biomechanical structural
      properties of mouse vertebrae.
AB  - STUDY DESIGN: Caudal vertebrae were obtained from male and female mice from two
      transgenic lines expressing an erythroid-specific human growth hormone transgene
      construct, and gender-matched, age-matched, non-transgenic control mice.
      OBJECTIVE: To characterize the effect of human growth hormone transgene
      expression on the biomechanical structural properties of caudal vertebrae in
      compression. SUMMARY OF BACKGROUND DATA: An increase in trabecular and cortical
      bone deposition caused by erythroid-specific human growth hormone transgene
      expression was demonstrated previously. METHODS: Compression tests were performed
      on individual caudal vertebrae (Ca4, Ca5, Ca6) obtained from male and female mice
      from two transgenic lines (TG420 and TG450) and nontransgenic control mice. Two
      age groups were evaluated: 12 weeks old and 6 months old. The data were used to
      obtain axial stiffness, maximum load, and energy to failure. RESULTS: Vertebrae
      from male TG420 transgenic mice produced significantly larger values for maximum
      load, energy to failure, and axial stiffness at both 12 weeks and 6 months in
      comparison with their age-matched non-transgenic male controls. Vertebrae from
      female TG420 transgenic mice produced similar responses at 6 months. Vertebrae
      from male TG450 transgenic mice showed significant increases in maximum load and
      energy to failure at 6 months. In general, the biomechanical properties of
      vertebrae were significantly larger in the 6-month age group than in the 12-week
      age group, and this increase was significantly greater in the transgenic mice
      than in the gender-matched control mice during the same time span. This process
      was also influenced by transgenic genotype and gender. CONCLUSIONS: Erythroid
      specific production of human growth hormone in transgenic mice resulted in
      significant increases in biomechanical properties of their caudal vertebrae in
      compression. The changes in the biomechanical properties were influenced by
      genotype, age, and gender.

PMID- 9921582
TI  - Rapid identification of Salmonella spp. phase 2 antigens of the H1 antigenic
      complex using "multiplex PCR".

PMID- 9921584
TI  - Occipital screw pullout strength. A biomechanical investigation of occipital
      morphology.
AB  - STUDY DESIGN: A three-group design with consistent pullout strength measures.
      OBJECTIVES: To determine pullout strength of three fixation types (unicortical
      screws, bicortical screws, wires) and to investigate their correlation with
      respect to occipital morphology. SUMMARY OF BACKGROUND DATA: A secured,
      multidirectional occipitocervical fusion requires internal fixation. Devices
      secured at occipital protuberance were suggested to offer the greatest pullout
      strength because of this region's thickness. METHODS: Twelve fresh human
      cadaveric occiputs were sketched with a grid delineating 21 fixation sites. Each
      site was drilled and hand-tapped. Four specimens were instrumented with
      unicortical screws on one side of the midline and bicortical screws on the other.
      Another four were instrumented with bicortical screws and wires, and the
      remaining four were instrumented with unicortical screws and wires. Two points on
      each specimen were secured with identical fixation to examine side-to-side
      symmetry. An MTS materials testing apparatus (MTS Systems Corporation, Eden
      Prairie, MN) was used to displace the fixators. Pullout strengths at different
      anatomic locations were recorded. RESULTS: The greatest pullout strength was at
      the occipital protuberance for all fixation types. The bicortical pullout
      strength was 50% greater than unicortical. The wire pullout strength was not
      significantly different from that of the unicortical screw (P > 0.05). Seventy
      eight percent of wires broke at 1100 N. Unicortical pullout strength at occipital
      protuberance was comparable with that of the bicortical screw at other locations.
      CONCLUSIONS: Unicortical screw fixation at occipital protuberance offers
      acceptable pullout strength without the potential complications of bicortical
      screws or wire fixation.

PMID- 9921585
TI  - Measurement of strain distributions within vertebral body sections by texture
      correlation.
AB  - STUDY DESIGN: A high-resolution strain measurement technique was applied to
      axially loaded parasagittal sections from thoracic spinal segments. OBJECTIVES:
      To establish a new experimental technique, develop data analysis procedures,
      characterize intrasample shear strain distributions, and measure intersample
      variability within a group of morphologically diverse samples. SUMMARY OF
      BACKGROUND DATA: Compression of intact vertebral bodies yields structural
      stiffness and strength, but not strain patterns within the trabecular bone.
      Finite element models yield trabecular strains but require uncertain boundary
      conditions and material properties. METHODS: Six spinal segments (T8-T10) were
      sliced in parasagittal sections 6-mm thick. Axial compression was applied in 25-N
      increments up to sample failure, then the load was removed. Contact radiographs
      of the samples were made at each loading level. Strain distributions within the
      central vertebral body were measured from the contact radiographs by an image
      correlation procedure. RESULTS: Intrasample shear strain probability
      distributions were log-normal at all load levels. Shear strains were concentrated
      directly inferior to the superior end-plate and adjacent to the anterior cortex,
      in regions where fractures are commonly seen clinically. Load removal restored
      overall sample shape, but measurable residual strains remained. CONCLUSIONS: This
      experimental model is a suitable means of studying low-energy vertebral
      fractures. The methods of data interpretation are consistent and reliable, and
      strain patterns correlate with clinical fracture patterns. Quantification of
      intersample variability provides guidelines for the design of future experiments,
      and the strain patterns form a basis for validation of finite element models. The
      results imply that strain uniformity is an important criterion in assessing risk
      of vertebral failure.

PMID- 9921586
TI  - Characteristics of pedicle screw loading. Effect of surgical technique on
      intravertebral and intrapedicular bending moments.
AB  - STUDY DESIGN: A static nondestructive bending analysis of pedicle screws inserted
      into vertebral analogues was conducted. Pedicle screw load was studied as a
      function of variables in insertion technique. OBJECTIVES: To determine how the
      sagittal bending moment in pedicle screws is affected by changes in pedicle screw
      length, insertional depth, and sagittal placement. BACKGROUND DATA: An
      unexpectedly high rate of clinical failure has been observed in pedicle screws
      used in short-segment instrumentation for unstable burst fractures. The majority
      of screws fail in sagittal bending within the pedicle. Little is known of the
      insertion technical factors that affect in situ loads incurred by pedicle screws.
      METHODS: Synthetic vertebral analogues were fabricated. Pedicle screws internally
      instrumented with strain gauges were used as load transducers to determine screw
      bending moments within the pedicle and body of the analogue. Analogues were
      loaded in compression to simulate loading of an unstable burst fracture. RESULTS:
      Screw bending moments within the pedicle increased 33% and 52% when screws were
      left 3 mm and 5 mm short of full insertion. Intrapedicular moments increased 20%
      to 29% in screws inserted superiorly or inferiorly within the pedicle. Thirty
      five-millimeter screws developed intrapedicular moments 16% higher than 40-mm and
      45-mm screws. CONCLUSIONS: In situ pedicle screw loads increased significantly as
      a direct result of variations in surgical technique. Screws left short of full
      insertion, placed off center in the sagittal plane of the pedicle, or less than
      40 mm long developed increased intrapedicular bending moments.

PMID- 9921587
TI  - Posterior stabilization of degenerative lumbar spondylolisthesis with a Leeds
      Keio artificial ligament. A biomechanical analysis in a porcine vertebral model.
AB  - STUDY DESIGN: The biomechanical characteristics of the Leeds-Keio artificial
      ligament (Neoligament LTD, England) were assessed in the posterior stabilization
      of degenerative lumbar spondylolisthesis in a porcine vertebral model.
      OBJECTIVES: To evaluate the biomechanical properties of this nonrigid system
      immediately after instrumentation and during cyclic loading. SUMMARY OF
      BACKGROUND DATA: Mochida et al reported an innovative method of posterior
      stabilization in which the Leeds-Keio artificial ligament was used as a nonrigid
      instrument. Since 1990, this system has been used successfully to treat a select
      group of patients with degenerative lumbar spondylolisthesis. METHODS: Five
      porcine motion segments (L4-L5) were tested in the intact, destabilized, and
      Leeds-Keio-instrumented conditions. Specimens were loaded in flexion and
      extension, and construct stiffness was measured during the initial loading cycle
      and at 250 cycle intervals for 1500 cycles. RESULTS: Biomechanical stability in
      the model of degenerative lumbar spondylolisthesis was inferior to that in the
      controls. The instability in the Leeds-Keio group significantly improved
      immediately after placement and after 1500 cycles. CONCLUSIONS: This system is
      effective in initially stabilizing an unstable degenerative lumbar
      spondylolisthesis model and maintains its stabilizing effect during cyclic
      loading. Therefore, it can offer patients with degenerative lumbar
      spondylolisthesis in the late static stage several advantages over other
      treatment methods.

PMID- 9921588
TI  - Morphologic limitations of posterior decompression by midsagittal splitting
      method for myelopathy caused by ossification of the posterior longitudinal
      ligament in the cervical spine.
AB  - STUDY DESIGN: This is a retrospective study of the morphologic limitations of
      posterior decompression for ossification of the posterior longitudinal ligament
      in the cervical spine. OBJECTIVES: To determine the morphologic limitations of
      the posterior approach in the management of ossification of the posterior
      longitudinal ligament. SUMMARY OF BACKGROUND DATA: Thirty-eight patients who
      underwent laminoplasty by midsagittal splitting for ossification of the posterior
      longitudinal ligament were reviewed. Fifteen patients were included in the
      noncontact group, in which the spinal cord was free of the ossified lesion after
      posterior decompression. Twenty-three patients were included in the contact
      group, in which the spinal cord was not free of the ossified lesion even after
      posterior decompression. METHODS: The preoperative sagittal alignment of the
      cervical spine and preoperative maximal thickness of ossification were compared
      between the two groups. In addition, the morphologic limitations of posterior
      decompression for ossification of the posterior longitudinal ligament were
      investigated. RESULTS: The following factors were found to contribute
      significantly to contact between the spinal cord and ossification of the
      posterior longitudinal ligament after posterior decompression: 1) lordosis of
      less than 10 degrees or kyphosis in the preoperative sagittal alignment, and 2)
      preoperative maximal thickness of ossification of more than 7 mm. CONCLUSIONS:
      Patients who exhibit significant risk factors for continued contact of the spinal
      cord should be morphologically considered for anterior decompression.

PMID- 9921589
TI  - The production of scoliosis after pinealectomy in young chickens, rats, and
      hamsters.
AB  - STUDY DESIGN: This study involved weekly radiographic examination of
      pinealectomized rats, hamsters, and chickens to observe the development of
      scoliosis. OBJECTIVES: To determine whether pinealectomy produces scoliosis in
      animals more closely related phylogenetically to humans than to chickens, namely
      rats and hamsters, which are representative of mammals. SUMMARY OF BACKGROUND
      DATA: Pinealectomy in 3-day-old chickens has consistently resulted in the
      development of scoliosis with many characteristics similar to those seen in
      patients with adolescent idiopathic scoliosis. It has not been determined whether
      this phenomenon is restricted solely to chickens or is applicable to other
      animals, especially those more closely related to humans. METHODS: The pineal
      gland was removed from young rats, hamsters, and chickens. All animals underwent
      radiography weekly to detect the development of any scoliosis. Weight and length
      measurements were also taken weekly, and serum melatonin levels were determined
      at the time the animals were killed. RESULTS: Scoliosis was not observed in
      either the rats or the hamsters. In contrast, scoliosis developed in 10 of 21
      chickens. Serum melatonin levels in all pinealectomized animals were zero.
      CONCLUSIONS: In contrast to the chickens, pinealectomy does not seem to cause
      scoliosis in either young rats or hamsters. The reasons for this discrepancy may
      include differences in the physiology and spinal morphology of the rat and
      hamster in comparison with the chicken. In the pinealectomized chickens, the
      results also suggest that future scoliosis development might be indicated by a
      significant increase in size when they are compared with pinealectomized chickens
      that do not develop scoliosis. Such differences in growth rates also distinguish
      patients with adolescent idiopathic scoliosis.

PMID- 9921591
TI  - Trunk muscle weakness as a risk factor for low back pain. A 5-year prospective
      study.
AB  - STUDY DESIGN: A 5-year prospective study. OBJECTIVES: To investigate trunk muscle
      weakness as a risk factor for low back pain in asymptomatic volunteers. SUMMARY
      OF BACKGROUND DATA: Muscle strength has not been sufficiently studied as a risk
      factor for low back pain. METHODS: The study participants included 30 male and 37
      female volunteers (mean age, 17 +/- 2 years), who neither reported nor had ever
      been treated for low back pain. Trunk muscle strength was measured isokinetically
      (60 degrees/sec), using the trunk extension and flexion and torso rotation units.
      The peak torques of the volunteers' extension, flexion, rightward rotation, and
      leftward rotation were measured, and the agonist/antagonist ratios were
      calculated as extension/flexion and left rotation/right rotation ratio. The
      volunteers then were followed prospectively for 5 years to determine the
      incidence of low back pain and were classified into a non-low back pain group
      (volunteers with no low back pain during the 5-year follow-up period) and a low
      back pain group (volunteers who experienced low back pain during this period).
      RESULTS: The low back pain group consisted of 8 male and 10 female volunteers.
      There were no significant differences between the non-low back pain group and the
      low back pain group regarding age, height, weight, the peak torque values, or the
      left rotation/right rotation ratio. However, the extension/flexion ratio of the
      low back pain group (men, 0.96 +/- 0.27; women, 0.77 +/- 0.19) demonstrated
      significantly lower values than that of the non-low back pain group (1.23 +/-
      0.28 and 1.00 +/- 0.16 for men and women, respectively, P < 0.05). CONCLUSIONS:
      An imbalance in trunk muscle strength, i.e., lower extensor muscle strength than
      flexor muscle strength, might be one risk factor for low back pain.

PMID- 9921590
TI  - Differentiating lumbar disc protrusions, disc bulges, and discs with normal
      contour but abnormal signal intensity. Magnetic resonance imaging with
      discographic correlations.
AB  - STUDY DESIGN: Independent evaluation by two observers of 132 lumbar discs in 45
      patients with chronic low back pain investigated by both magnetic resonance
      imaging and discography. OBJECTIVES: To assess some of the fundamental
      differences between lumbar disc protrusions, disc bulges, and discs with normal
      contour but abnormal signal intensity on T2-weighted magnetic resonance images.
      SUMMARY OF BACKGROUND DATA: Moderate interobserver agreement has been reported
      when the morphologic terms normal, bulge, protrusion, and extrusion are used. The
      validity of this nomenclature remains unknown. METHODS: Discs were evaluated on
      magnetic resonance images for central and peripheral signal characteristics,
      height, contour, and nerve root compression. Discograms were classified according
      to degrees of disc degeneration, disruption, and pain reproduction. RESULTS: Loss
      of intervertebral height or abnormal signal intensity on magnetic resonance
      imagery was significantly associated with disc disruptions extending into or
      beyond the outer anulus on discograms. All 23 protrusions (100%) and 12 of 15
      disc bulges (80%) were associated with Stage 2 or 3 anular disruptions and, in
      most instances, similar or exact reproduction of pain during disc injection.
      There was no significant difference between disc protrusions, disc bulges, and
      discs with normal contour but abnormal signal, with respect to degree of disc
      degeneration, extent of disruptions, or presence of discogenic pain. CONCLUSIONS:
      In patients with chronic low back pain, loss of disc height or abnormal signal
      intensity is highly predictive of symptomatic tears extending into or beyond the
      outer anulus. Disc bulges and disc protrusions do not represent discs with
      significantly different internal architecture, based on the findings of
      discography, and are no more suggestive of symptomatic tears than discs showing
      normal contour but decreased height or abnormal signal intensity.

PMID- 9921592
TI  - The effect of operative position and short-segment fusion on maintenance of
      sagittal alignment of the lumbar spine.
AB  - STUDY DESIGN: A retrospective radiographic assessment of the maintenance of
      sagittal alignment in patients undergoing short-segment instrumented fusions in a
      knee-chest position. OBJECTIVE: To determine whether the use of the knee-chest
      position adversely effects the maintenance of lumbar sagittal alignment in
      patients undergoing short-segment instrumented fusions of the lumbar spine.
      SUMMARY OF BACKGROUND DATA: Previous authors have demonstrated that lumbar
      lordosis is reduced in the knee-chest position, but it is unknown whether the
      kneeling position adversely affects the maintenance of lumbar lordosis in short
      segment instrumented fusions during the follow-up period. METHODS: Twenty-eight
      patients (17 men and 11 women, 20-72 years of age) were reviewed retrospectively,
      having undergone short-segment fusions in the kneeling position. Seven patients
      underwent posterior spinal fusion from L4 to L5, 13 patients from L5 to S1, and 8
      patients from L4 to S1. Transpedicular instrumentation and autogenous iliac crest
      bone grafting was used in all cases. Radiographs were assessed for sacral tilt,
      lumbar lordosis, and intervertebral angulation. Data were analyzed with repeated
      measures analysis of variance. RESULTS: The minimum follow-up period was 33
      months. For all 28 patients, lumbar lordosis measured 51 degrees before surgery,
      37 degrees during surgery (P = 0.0001), and 50 degrees after surgery (P =
      0.6135). In patients undergoing L4-S1 posterior spinal fusion, sacral tilt
      measured 49 degrees before surgery and 45 degrees after surgery (P = 0.039).
      Although overall lumbar lordosis was maintained, lordosis was shifted proximally
      in the lumbar spine, increasing at L1-L4 from 19 degrees before surgery to 24
      degrees after surgery, while decreasing at L4-S1 from 32 degrees before surgery
      to 26 degrees after surgery. CONCLUSION: Overall lumbar lordosis is well
      maintained in patients undergoing short-segment instrumented fusion in the
      kneeling position. With compensatory lordosis being shifted proximally and sacral
      tilt not returning to the preoperative status in L4 to S1 fusions, caution should
      be exercised in using the kneeling position for longer instrumented lumbar
      fusions.

PMID- 9921593
TI  - Spinous process osteotomies to facilitate lumbar decompressive surgery.
AB  - STUDY DESIGN: A technique for lumbar decompression using spinous process
      osteotomies is described, and the outcomes are studied prospectively. OBJECTIVE:
      To describe a technique that affords a wide exposure for decompression while
      minimizing damage to surrounding tissues, and to analyze the outcomes formally
      using the technique. SUMMARY OF BACKGROUND DATA: Commonly used techniques of
      lumbar decompression, which include bilateral takedown of paraspinal musculature
      and aggressive bony resection, can result in significant iatrogenic sequelae,
      whereas minimally invasive techniques often provide inadequate visualization
      and/or decompression. METHOD: Unilateral limited takedown of the multifidus is
      undertaken, followed by spinous process osteotomies at the involved levels. The
      spinous processes with the attached interspinous/supraspinous ligaments are then
      retracted. A complete "trumpeted" decompression is then undertaken. Fifty
      consecutive patients undergoing the procedure were analyzed prospectively and at
      follow-up by an independent observer using a validated functional outcome
      measure, a visual analog pain scale, and a patient satisfaction score. RESULTS:
      Functional outcome scores improved on average by 47%, pain levels were reduced by
      66%, and high satisfaction rates were reported by 83% of patients. CONCLUSIONS:
      The technique affords excellent visualization and a wide area available for
      Kerrison use and angulation while minimizing destruction to tissues not directly
      involved in the pathologic process, including the paraspinal musculature as well
      as the interspinous/supraspinous ligament complex and facets. Additionally, it
      minimizes dead space and improves the cosmetic result.

PMID- 9921594
TI  - Anterior decompression with single segmental spinal interbody fusion for lumbar
      burst fracture.
AB  - STUDY DESIGN: The clinical and radiologic records for seven patients with lumbar
      burst fracture who underwent anterior decompression with single segmental
      interbody fusion were reviewed. OBJECTIVE: To determine the clinical results
      obtained with this method and its influence on the intervertebral disc
      degeneration inferior to the fusion. SUMMARY OF BACKGROUND DATA: Some patients
      with Denis' type B fracture can tolerate one-segment anterior fusion. However,
      there is no reliable information in the literature regarding the juxtafusional
      disc degeneration after one-segment fusion. METHODS: Seven patients with type B
      lumbar burst fractures, including four with cleavage fracture of the lower
      endplate, underwent anterior single segmental fusion; three patients underwent
      surgery with no instrumentation, and four underwent surgery with Kaneda
      instrumentation. The mean follow-up period lasted 85 months. The kyphosis angle
      and inferior intervertebral disc height adjacent to the fusion were measured
      before and after surgery. Pain and working status were evaluated using the scales
      proposed by Denis et al. RESULTS: Significant correction loss was obtained 1 year
      after surgery in the patients in whom no instrumentation was used (7.3 +/- 0.6
      degrees), compared with the correction loss in patients whose surgery included
      the use of instrumentation (0.3 +/- 0.5 degree; P = 0.00001). No further
      correction losses were seen in either group at the final follow-up examination.
      No marked reduction in disc height was observed in any patient, including the
      four patients with cleavage fracture of the lower endplate. All patients returned
      to their previous occupation; five patients were rated as P1 (no pain) and W1
      (returned to heavy labor), and two patients were rated as P2 (minimal pain) and
      W2 (return to heavy labor with lifting restrictions) at the final follow-up
      examination. CONCLUSIONS: There was slight correction loss within 1 year when no
      instrumentation was used, but this deformity did not affect the clinical results.
      The results provided no evidence that cleavage fracture of the lower endplate
      accelerates degeneration of the adjacent intervertebral disc.

PMID- 9921595
TI  - Lymphangioma presenting as a dumbbell tumor in the epidural space of the lumbar
      spine.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of
      lymphangioma presenting as a dumbbell-shaped tumor in the epidural space of the
      lumbar spine. SUMMARY OF BACKGROUND DATA: Dumbbell tumor of the spine is not
      uncommon. Although the pathogenesis of such tumors varies widely, lymphangioma
      has not been reported previously, to these authors' knowledge. METHODS: A 56-year
      old woman with pain in the lower back and left leg was examined by plain
      radiographs and magnetic resonance imaging before surgery. Treatment consisted of
      the usual technique of surgical resection of the tumor. Histopathologic study of
      the resected material confirmed the diagnosis. Postoperative follow-up assessment
      was performed by magnetic resonance imaging. RESULTS: Magnetic resonance imaging
      demonstrated a dumbbell tumor in the epidural canal area of the lumbar spine.
      Histopathologic diagnosis of the resected tumor was cavernous lymphangioma.
      CONCLUSION: To the authors' knowledge, this is the first reported case of
      lymphangioma presenting as a spinal dumbbell tumor. Further observation is
      recommended because of the possibility of local recurrence.

PMID- 9921597
TI  - Whiplash injury. Biomechanical experimentation.

PMID- 9921596
TI  - The solitary intraspinal vertebral osteochondroma. An unusual cause of
      compressive myelopathy: features and literature review.
AB  - STUDY DESIGN: Reports of four patients with compressive myelopathy from solitary
      intraspinal vertebral osteochondromas. OBJECTIVES: To evaluate the clinical
      presentation and radiographic findings of patients with intraspinal
      osteochondroma with compressive myelopathy and to review the relevant English
      language medical literature. SUMMARY OF BACKGROUND DATA: Involvement of the spine
      by solitary osteochondromas is rare. The addition of the current four cases to
      those already reported makes a total of 41 published cases of solitary vertebral
      osteochondromas with spinal cord compression. METHODS: Clinical histories,
      computed tomographic studies, magnetic resonance imaging studies, routine
      radiographs, and/or myelographic studies of the lesions were reviewed. A review
      of the English-language medical literature also was done. RESULTS: Patients
      gradually improved or symptoms stopped progressing after surgical removal of the
      lesions. Although magnetic resonance imaging is the preferred method for
      localizing the lesion, computed tomography can be more specific, because of its
      sensitivity, when the diagnosis is in doubt. CONCLUSIONS: Osteochondromas
      represent a hyperplastic-dysplastic disturbance of bone from progressive
      endochondral ossification. The tumors slowly enlarge, creating insidious but
      progressive symptoms. Magnetic resonance imaging, computed tomography, and
      postmyelogram computed tomography are useful in evaluating the size and extent of
      spinal osteochondromas as a cause of spinal cord compression.

PMID- 9921598
TI  - A review and methodologic critique of the literature refuting whiplash syndrome.
AB  - The validity of whiplash syndrome has been a source of debate in the medical
      literature for many years. Some authors have published articles suggesting that
      whiplash injuries are impossible at certain collision speeds; others have stated
      that the problem is psychological, or is feigned as a means to obtain secondary
      financial gain. These articles contradict the majority of the literature, which
      shows that whiplash injuries and their sequelae are a highly prevalent problem
      that affects a significant proportion of the population. The authors of the
      current literature critique reviewed the biomedical and engineering literature
      relating to whiplash syndrome, searching for articles that refuted the validity
      of whiplash injuries. Twenty articles containing nine distinct statements
      refuting the validity of whiplash syndrome were found that fit the inclusion
      criteria. The methodology described in these articles was evaluated critically to
      determine if the authors' observations regarding the validity of whiplash
      syndrome were scientifically sound. The authors of the current critique found
      that all of the articles contained significant methodologic flaws with regard to
      their respective authors' statements refuting the validity of whiplash syndrome.
      The most frequently found flaws were inadequate study size, nonrepresentative
      study sample, nonrepresentative crash conditions (for crash tests), and
      inappropriate study design. As a result of the current literature review, it was
      determined that there is no epidemiologic or scientific basis in the literature
      for the following statements: whiplash injuries do not lead to chronic pain, rear
      impact collisions that do not result in vehicle damage are unlikely to cause
      injury, and whiplash trauma is biomechanically comparable with common movements
      of daily living.

PMID- 9921599
TI  - Whiplash: heading for a higher ground.

PMID- 9921600
TI  - Phospholipase A2 activity in herniated lumbar discs.

PMID- 9921601
TI  - Quebec Task Force's whiplash study.

PMID- 9921602
TI  - Patients with low back pain.

PMID- 9921603
TI  - Experiences of a biostatistician on a U.K. Research Ethics Committee.
AB  - Poorly planned research liable to produce misleading results is unethical. Local
      Research Ethics Committees in the U.K. have a duty to assess the scientific merit
      of studies, of which statistical aspects are an essential component, yet few have
      access to a biostatistician. I present personal experience of the workload
      involved and general issues arising in submissions to a large teaching NHS
      Hospitals Trust, with emphasis on sample size. These general issues should apply
      to analogous committees in countries other than the U.K. The opportunity to
      influence the quality of all local medical research is argued to be reasonable
      incentive for more voluntary involvement by statisticians.

PMID- 9921604
TI  - Extracting summary statistics to perform meta-analyses of the published
      literature for survival endpoints.
AB  - Meta-analyses aim to provide a full and comprehensive summary of related studies
      which have addressed a similar question. When the studies involve time to event
      (survival-type) data the most appropriate statistics to use are the log hazard
      ratio and its variance. However, these are not always explicitly presented for
      each study. In this paper a number of methods of extracting estimates of these
      statistics in a variety of situations are presented. Use of these methods should
      improve the efficiency and reliability of meta-analyses of the published
      literature with survival-type endpoints.

PMID- 9921605
TI  - Sample size review in a head injury trial with ordered categorical responses.
AB  - Between 1993 and 1996, a total of 452 patients were entered into a randomized
      trial evaluating eliprodil (a non-competitive NMDA receptor antagonist) in
      patients suffering from severe head injury. The primary efficacy analysis
      concerned the Glasgow Outcome Score (GOS), six months after randomization. This
      outcome was classified into three ordered categories: good recovery; moderate
      disability, and the worst category made up by combining severe disability,
      vegetative state and dead. A sample size calculation was performed prior to the
      commencement of the study, using a formula which depends on the anticipated
      proportions of patients in the three different outcome categories, the
      proportional odds assumption and on the relationship between outcome and
      prognostic factors such as Glasgow Coma Score at entry. Owing to uncertainty
      about the influence of prognostic factors, and about the proportion of patients
      in the three GOS categories, a blinded sample size review was planned. This
      review was performed on the basis of the first 93 patients to respond, and this
      led to an increase in the sample size from 400 to 450. In this paper the pre
      trial simulations showing that the type I error rate would be influenced and the
      power would be preserved will be presented, and the implementation of the
      procedure will be described.

PMID- 9921606
TI  - Robust and realistic approaches to carry-over.
AB  - The relationship between choice of model for carry-over and choice of efficient
      cross-over design is studied in particular with reference to two treatment
      designs in four periods and two sequences. The effect of model miss-specification
      is also examined. It is concluded that previous claims regarding efficient
      designs are not necessarily reasonable.

PMID- 9921607
TI  - Incorporation of family history in logistic regression models.
AB  - For diseases with a genetic component, logistic regression models are presented
      that incorporate family history in a quantitative way. In the largest model,
      every type of relative has their own regression coefficient. The other two models
      are submodels, which incorporate family history either by the number of cases in
      the family minus its expectation or by a weighted number of cases in the family
      minus its expectation. For various genetic effects, namely polygenic and
      autosomal dominant effects, the performance of these simple logistic models is
      studied. First, the predictive values of the logistic and true genetic models are
      computed and compared. Secondly, a simulation study is carried out to investigate
      the effects of estimation of the parameters in a small data set. Thirdly, the
      logistic models are fitted to a data set of Von Willebrand Factor responses of
      target individuals and their families; in these models, family history has a
      significant effect. The conclusion is that for the genetic effects considered the
      logistic models perform well.

PMID- 9921608
TI  - Assessing treatment-time interaction in clinical trials with time to event data:
      a meta-analysis of hypertension trials.
AB  - Exploration of the variation of treatment effect over time in randomized clinical
      trials with low event rates is limited by lack of power. A meta-analysis on
      individual patient data from such trials can partly solve the problem, but brings
      other computational difficulties. Using an example in hypertension, we describe
      appropriate methods for graphical description and statistical modelling of
      treatment-time interactions in large data sets. Also, a method is developed for
      determining the total number of events required to detect treatment-period
      interactions of plausible magnitude. We conclude that trialists tend to
      overinterpret the observed data when looking for potential treatment-time
      interactions by visual comparisons of survival curves, failing to realize the
      substantial amounts of data that are needed for their detection and estimation.

PMID- 9921609
TI  - Gibbs sampler for the logistic model in the analysis of longitudinal binary data.
AB  - Logistic mixed-effects models constitute a natural framework to study
      longitudinal binary response variables when the question addressed with the data
      is related to covariate effects within persons. However, the computations of the
      likelihoods are generally tedious and require the resolution of integrals which
      have no analytical solution. In this paper, we study a logistic mixed-effects
      model in a Bayesian framework and use the Gibbs sampler to overcome the current
      computational limitations. From a study of side-effects occurring during plasma
      exchanges, we explore the issues of bayesian formulation, model parametrization,
      choice of the prior distributions, diagnosing convergence, comparison between
      models and model adequacy. Finally, we show that a Bayesian random-effects model
      is useful to facilitate prediction.

PMID- 9921610
TI  - Ordinal invariant measures for individual and group changes in ordered
      categorical data.
AB  - Subjective judgements of complex variables are commonly recorded as ordered
      categorical data. The rank-invariant properties of such data are well known, and
      there are various statistical approaches to the analysis and modelling of ordinal
      data. This paper focuses on the non-additive property of ordered categorical data
      in the analysis of change. A rank-invariant non-parametric method of analysis is
      presented that is valid regardless of the number of response categories. The
      unique feature of this method is the augmented ranking approach that is related
      to the joint distribution of paired observations. This approach makes it possible
      to measure separately the individual order-preserved categorical changes, which
      are attributable to the group change, and the individual categorical changes that
      are not consistent with the pattern of group change. The method is applied to
      analysis of change in a three-point scale and in a visual analogue scale of
      continuous ordinal responses.

PMID- 9921611
TI  - Modelling the cause of dependency with application to filaria infection.
AB  - A preliminary data set is analysed containing filaria specific IgG4 and IgE
      levels and the presence of microfilariae of 196 people from families of a village
      in Indonesia. Since filaria infected people may not be microfilaria positive, a
      filaria infection can easily be missed. First, the probabilities of a filaria
      infection are estimated from the IgG4 levels and the presence of microfilariae
      using the EM algorithm. By dichotomizing these probabilities, infection status is
      estimated for each person. Then for IgG4, IgE and infection status, the
      correlations between observations are modelled. Three causes for a correlation
      are considered, namely genetic, intra-uterine or environmental effects. The
      correlation structure of the genetic and the intra-uterine effects are quite
      similar and consequently it may be difficult to disentangle them. Empirical
      variograms are plotted and the various variance components are estimated by
      maximizing the log-likelihood. For infection status an environmental effect is
      found and for IgG4 and IgE levels genetic effects are found.

PMID- 9921612
TI  - ["Emerging" viral zoonoses in native animals who can be the host in the
      Netherlands].
AB  - Viral zoonotic diseases can be defined as 'Viral diseases transmitted from
      vertebrate animals to man'. Viral zoonoses have been emerging and re-emerging
      throughout history and can cause serious diseases and disease outbreaks in human
      populations. This paper deals with emerging viral zoonotic infections that have
      hosts in native species and can be a hazard for the human population in the
      Netherlands. Rabies virus, hantavirus, influenza virus tick-borne encephalitis
      virus, borna disease virus and prions will be discussed.

PMID- 9921613
TI  - [Panel on Nutrition and Dietetics of Companion Animals. Gastrointestinal patients
      and nutrition].

PMID- 9921614
TI  - [Insurer Movir warns against government. Labor unsuitability in growth of free
      appeal].

PMID- 9921615
TI  - [Big meeting day about foot-and-mouth disease. Are there any cattle herds left
      after foot-and-mouth disease?].

PMID- 9921616
TI  - 3D ultrasound tissue motion tracking using correlation search.
AB  - Several methods for ultrasound tissue motion tracking and blood velocity
      estimation have been proposed and clinically applied. While providing valuable
      information to the clinician that was not obtainable from B-mode anatomical
      imaging, these methods still suffer from various fundamental and practical
      limitations that compromise their performance in certain clinical situations. A
      significant limitation is the inability of most of these methods to estimate the
      complete 3D motion or velocity vectors. With the introduction of ultrasound
      volumetric imaging, the need for a method that is capable of obtaining the
      complete motion vector is even more pressing. In this paper, we investigate the
      implementation of a correlation search scheme to estimate the 3D motion vectors
      using successive volumetric ultrasound scans. We present tracking results for
      motion along different axes and discuss the advantages and limitations of
      performing the correlation search in 3D.

PMID- 9921617
TI  - Differential attenuation imaging for the characterization of high intensity
      focused ultrasound lesions.
AB  - High intensity focused ultrasound (HIFU) is an effective technique for creating
      coagulative necrotic lesions in biological tissue, with a view to treating
      localized tumors. Although good results have already been obtained, notably in
      urology, current systems lack a real time monitoring system to check the efficacy
      of the treatment procedures. This study describes the development and assessment
      of a noninvasive system for making local measurements of attentuation variations
      during HIFU treatment procedures. An apparatus (Ablatherm, Edap-Technomed,
      France), combining a 2.5 MHz therapeutic transducer and a 5.5 MHz twin plane
      imaging probe (connected to an ultrasound scanner), was used to produce lesions.
      The rf signals needed to calculate the attenuation were recorded as outputs from
      the ultrasound scanner, before and after the high intensity firing sequences,
      which were performed on ten pieces of porcine liver. Each firing sequence
      involved producing a lesion volume comprising 42 individual lesions. A number of
      recordings were also made without producing lesions, in order to test the
      reproducibility of the measurements. The attenuation function was evaluated
      locally using the centroid and the multinarrowband methods. Initially, changes in
      the integrated attenuation alpha (mean attenuation in the 4-7 MHz range) and the
      attenuation slope beta were examined for the lesion volume. beta values did not
      vary significantly within this range, whereas alpha values varied significantly
      (in the region of 86% of the initial level) in comparison to measurements
      performed without forming lesions. The differential attenuation delta alpha
      (representing local variations in alpha) was subsequently used to generate images
      revealing the lesion areas. There was a strong similarity between these 'delta
      alpha images' and the lesion volumes defined by the operator. 'delta alpha
      images' offer several advantages over existing attenuation imaging techniques.
      Any problems related to the heterogeneity of the medium are eliminated, since
      only the change in attenuation is taken into account. Furthermore, there is no
      need to compensate for diffraction when estimating delta alpha, as the rf signals
      are captured in exactly the same positions before and after treatment. This
      technique can be used during in vivo treatment procedures. It can be implemented
      in real time, since the computational algorithms (based primarily on FFT
      calculations) are very fast. The technique should provide clinical practitioners
      with valuable qualitative and quantitative information for use in HIFU ultrasound
      surgery.

PMID- 9921618
TI  - Effects of tissue anisotropy on the spectral characteristics of ultrasonic
      backscatter measured with a clinical imaging system.
AB  - In this paper, we report the effects of inherent tissue anisotropy on the
      spectral properties of backscattered ultrasound when measured with a commercially
      available imaging system. We insonified five specimens of bovine tendon immersed
      in a water tank and rotated in 10 degrees increments while being imaged with a
      Hewlett-Packard Sonos 1500 system. The backscattered RF signals corresponding to
      each angle of insonification were digitized and the spectral characteristics of
      the backscattered ultrasound were determined. The mean anisotropy, defined as the
      average difference between values at perpendicular and parallel insonification,
      for band-limited estimates of backscattered power, centroid frequency, upper-band
      to lower-band power ratio, and upper-band to total-band power ratio were found to
      be 24.6 +/- 1.1 dB, 142 +/- 27 kHz, 32 +/- 13%, and 22 +/- 5%, respectively (mean
      +/- SE). The magnitude of each of these backscatter spectral parameters was
      larger at perpendicular insonification compared with the corresponding values at
      parallel insonification, consistent with previous measurements of the inherent
      anisotropy of ultrasonic attenuation and backscatter in tissue.

PMID- 9921619
TI  - Ultrasound image texture analysis for characterizing intramuscular fat content of
      live beef cattle.
AB  - The primary factors in determining beef quality grades are the amount and
      distribution of intramuscular fat percentage (IMFAT). Texture analysis was
      applied to ultrasound B-mode images from ribeye muscle of live beef cattle to
      predict its IMFAT. We used wavelet transform (WT) for multiresolutional texture
      analysis and second-order statistics using a gray-level co-occurrence matrix
      (GLCM) technique. Sets of WT- and GLCM-based texture features were calculated
      from ultrasonic images from 207 animals and linear regression methods were used
      for IMFAT prediction. WT-based features included energy ratios, central moments
      of wavelet-decomposed subimages and wavelet edge density. The regression model
      using WT features provided a root mean square error (RMSE) of 1.44 for prediction
      of IMFAT using validation images, while that of GLCM features provided an RMSE of
      1.90. The prediction models using the WT features showed potential for objective
      quality evaluation in the live animals.

PMID- 9921620
TI  - Shielding of piezoelectric ultrasonic probes in Hall effect imaging.
AB  - This paper addresses significant sources of electromagnetic noise in Hall effect
      imaging. Hall effect imaging employs large electrical pulses for signal
      generation and high sensitivity ultrasonic probes for signal reception. Coherent
      noise arises through various coupling mechanisms between the excitation pulse and
      the probe. In this paper, the coupling mechanisms are experimentally isolated and
      theoretically analyzed. Several methods of shielding the probe from
      electromagnetic interference are devised and tested. These methods are able to
      reduce the noise to levels below the random thermal noise, thereby improving the
      signal-to-noise ratio in HEI by two orders of magnitude.

PMID- 9921621
TI  - Normal haematological and serum biochemical values of Eurasian otters (Lutra
      lutra) from a Scottish rehabilitation centre.
AB  - Blood samples were taken from 47 clinically normal, wild-born Eurasian otters
      (Lutra lutra) before they were released from a rehabilitation centre in Scotland
      between August 1990 and March 1996. Serum biochemistry profiles were determined
      for 47 animals and haematological profiles for 41, and the results from males,
      females, and animals under or over one year of age were analysed as separate
      groups and as pooled populations. The normal ranges for a wide variety of
      haematological and serum biochemical parameters of the Eurasian otter are
      presented, and significant differences with age and sex are detailed.

PMID- 9921622
TI  - Abattoir survey of congenital reproductive abnormalities in ewes.
AB  - A survey of abnormalities of the reproductive tract of female sheep was
      undertaken at two abattoirs in the south west of England over a period of 12
      months. During the survey, 9970 reproductive tracts from cull ewes and 23,536
      tracts from nulliparous sheep (prime lambs and hoggets) were examined. A total of
      655 (6.57 per cent) ewes and 459 (1.95 per cent) nulliparous sheep had
      abnormalities of the reproductive tract. Of these, congenital abnormalities of
      the paramesonephric ducts accounted for 2.4 per cent of the ewes and 7.4 per cent
      of the nulliparous sheep, congenital abnormalities of the ovaries accounted for
      2.6 per cent of the ewes and 7.4 per cent of the nulliparous sheep and cystic
      structures that were considered to have been of congenital origin accounted for
      27.2 per cent of the ewes and 52.7 per cent of the nulliparous sheep. The most
      common lesion was paraovarian cysts (26.6 per cent of ewes and 39.0 per cent of
      nulliparous sheep), but few of these appeared to have affected the sheep's
      reproductive function. Several specific conditions were recorded, including some
      described for the first time in sheep. Uterus unicornis occurred in 20 sheep and
      other forms of segmental aplasia of parts of the paramesonephric ducts occurred
      in a further 13 animals. Uterus didelphys occurred in six sheep, and 11 animals
      were intersex. Intersex sheep had vestigial structures that were derived from the
      paramesonephric ducts, hypoplastic or masculinised gonads and some had
      masculinised external genitalia. Ovarian hypoplasia occurred in 34 sheep, and in
      a further 12 mainly nulliparous animals, the ovaries were fused. Sixty
      nulliparous animals and two ewes had hydatids of Morgagni.

PMID- 9921624
TI  - Ultrasonographic imaging of canine mammary tumours.
AB  - The efficiency and reliability of an ultrasonographic technique for evaluating
      mammary neoplasms was tested in 19 female dogs with palpable tumours. A 7.5 MHz
      linear-array ultrasound transducer was used, with an aqueous stand-off pad
      between the probe and the skin. The ultrasonographic images were used to evaluate
      the shape, size and echogenicity of the mammary lesions, and their relationship
      with other tissues. The tumours were excised and analysed histologically. A
      comparison of the ultrasonographic and histological findings revealed that the
      ultrasonographic images of nine of the 11 malignant tumours had irregular margins
      and were polymorphous in shape, all 11 were heterogeneous in their internal
      echogenicity, seven had acoustic shadowing and three showed acoustic enhancement.
      In contrast, seven of the eight benign tumours had regular margins and were
      spherical or oval in shape, all eight were homogeneous in their internal
      echographic pattern, seven had edge shadowing, and all eight showed acoustic
      enhancement. Moreover, six of the 11 malignant neoplasia were invasive, whereas
      all the benign tumours were isolated.

PMID- 9921623
TI  - Association between milk somatic cell counts up to 400,000 cells/ml and clinical
      mastitis in French Holstein cows.
AB  - The relationship between somatic cell counts (SCCs) up to 400,000 cells/ml in
      individual cows and clinical mastitis was studied by collecting monthly records
      for a year from 101 Holstein herds in the west of France. Monthly records
      obtained after any case of clinical mastitis occurring within the lactation were
      excluded. The resulting dataset consisted of 29,700 records from 4677 cows. The
      data were analysed by the logistic regression method. Herd, lactation number,
      calendar month, milk production, stage of lactation on the day of test, and SCC
      on previous test days were assumed to affect the likelihood of clinical mastitis.
      There was no significant relationship between SCC and the subsequent occurrence
      of clinical mastitis for an SCC up to 100,000 cells/ml, but the risk of clinical
      mastitis increased as the SCC increased up to 400,000 cells/ml. These results
      suggest that in individual cows, a low SCC recorded after five days in milk does
      not lead to an increased risk of clinical mastitis.

PMID- 9921625
TI  - Isolation of spirochaetes from an incident of severe virulent ovine footrot.

PMID- 9921627
TI  - Control of rabbit viral haemorrhagic disease in Benin by vaccination.

PMID- 9921628
TI  - Encephalitozoon hellem infection in a yellow-streaked lory (Chalcopsitta
      scintillata) imported from Indonesia.

PMID- 9921626
TI  - Investigation of a possible role for Chlamydia in a new disease syndrome in dairy
      cattle.

PMID- 9921629
TI  - Carriage of pathological samples.

PMID- 9921630
TI  - Multiple antibiotic resistance in Salmonella.

PMID- 9921631
TI  - Importation and use of medicines by farmers.

PMID- 9921632
TI  - Dealing with 'exotic' diseases.

PMID- 9921634
TI  - Updating the Veterinary Surgeons Act.

PMID- 9921633
TI  - Equine viral arteritis risk from imported semen.

PMID- 9921635
TI  - Updating the Veterinary Surgeons Act.

PMID- 9921636
TI  - Free-living wild boar in south-east England.

PMID- 9921637
TI  - Floppy pinnae in Siamese cats.

PMID- 9921638
TI  - Energy substrates and amino acids provided during in vitro maturation of bovine
      oocytes alter acquisition of developmental competence.
AB  - Energy substrates and amino acids were evaluated for supporting acquisition of
      developmental competence by bovine cumulus-oocyte complexes during in vitro
      maturation. The basic culture medium (Basic Medium-3) used for in vitro
      maturation of oocytes was modified to produce six media containing glucose or
      glutamine with lactate or pyruvate, or glucose + glutamine, or glucose + 11 amino
      acids; a seventh (control) medium was TCM199. All media contained polyvinyl
      alcohol, gonadotropins, epidermal growth factor and oestradiol. Following
      maturation, oocytes were incubated in medium TALP for fertilisation, then cumulus
      cells were removed and presumptive embryos cultured for 48 h in a chemically
      defined medium (HECM-6) followed by 120 h in medium TCM199 + bovine calf serum.
      Six substrate treatments yielded similar first cleavage responses (66-78%) at 72
      h post-insemination; however, blastocyst development at 192 h varied
      significantly. Oocytes matured in medium with glucose + 11 amino acids gave the
      best blastocyst development: 21% of inseminated oocytes or 25% of 2-cell embryos.
      Cumulus expansion in HECM-6 required glucose with either glutamine, 11 amino
      acids or lactate, or glutamine + lactate. We conclude that (1) the type of energy
      substrate or nutrient supplied during in vitro maturation of oocytes profoundly
      affects subsequent developmental competence; (2) oocyte maturation in simple
      medium containing glucose with lactate or 11 amino acids or glutamine, or lactate
      + glutamine, can support development equally as well as the complex medium,
      TCM199; and (3) media supporting at least moderate cumulus expansion during
      oocyte maturation also support subsequent blastocyst development.

PMID- 9921639
TI  - Isolation and collection of two populations of viable sperm cells from the pollen
      of Plumbago zeylanica.
AB  - A protocol is described for individually collecting two populations of sperm
      cells, Svn and Sua, from pollen of Plumbago zeylanica. Pollen grains were burst
      in 10 mM MOPS buffer containing 0.8 M mannitol (pH 4.6). Paired sperm cells
      released from pollen were separated using a microinjector. Svn and Sua were then
      collected individually with a microinjector, based upon known size differences.
      Collected sperm cells were washed with isolation medium and transferred to liquid
      nitrogen until use. Fluorochromatic reaction (FCR) test of isolated sperm cells
      showed a positive reaction, indicating that the isolated sperm cells are viable;
      most of the sperm cells retain viability for at least 2 h.

PMID- 9921640
TI  - Effects of follicle-stimulating hormone, bovine somatotrophin and okadaic acid on
      cumulus expansion and nuclear maturation of blue fox (Alopex lagopus) oocytes in
      vitro.
AB  - The meiotic competence and meiosis resumption of Blue fox (Alopex lagopus)
      oocytes from anoestrous animals were followed. Oocyte-cumulus complexes (OCC)
      were cultured in modified TC 199 medium with or without FSH, recombinant bovine
      somatotrophin (bST) and okadaic acid (OA). The results showed that oocytes less
      than 100 microns in diameter did not achieve germinal vesicle breakdown (GFBD) by
      72 h of culture, which indicates their meiotic incompetence. Oocytes larger than
      100 microns in diameter underwent GVBD after 48 h of culture (27%) and reached
      metaphase II (MII) after 72 and 96 h (20% and 27%) in control medium. Both bST
      and OA accelerated resumption of meiosis (bST: 55% GVBD and 42% MII after 48 h;
      OA: 66% GVBD after 18 h). In contrast, FSH significantly reduced meiosis
      resumption (only 3% GVBD and MII after 72 h) and induced changes in the shape of
      cumulus granulosa (CG) cells and F-actin assembly typical for cumulus expansion.
      However, the innermost layers of CG cells (corona radiata) remained connected
      with the oocyte via gap junctions until the end of culture. Cumuli of oocytes
      cultured in control, bST-supplemented or OA-supplemented medium did not expand
      (changes in cell shape and F-actin redistribution did not occur). Moreover,
      especially in media with bST and OA an increased detachment and rapid
      disconnection of their gap junctions with the oocyte were observed. These results
      suggest that under in vitro conditions FSH stimulates expansion of the CG cells
      and the attached membrana granulosa cells but in contrast it secures heterologous
      gap junctions between cytoplasmic processes of the corona radiata cells and
      oolemma during 3 days of culture. Thus, in agreement with the in vivo situation
      in which Canidae oocytes are ovulated in the GV stage, the cumulus, mainly corona
      radiata cells, controls resumption of meiosis in Blue fox oocytes under in vitro
      conditions also.

PMID- 9921642
TI  - Mouse oocytes and parthenogenetic eggs lose the ability to be penetrated by
      spermatozoa after fusion with zygotes.
AB  - Fertilised mouse eggs develop the oolemma block to sperm penetration within 1 h.
      This block makes zona-free eggs at the pronuclear stage (zygotes) fully resistant
      to sperm penetration. In this study we investigated whether this block can spread
      -as a result of cell fusion--to the oolemma of eggs that are competent to be
      penetrated by spermatozoa. Preovulatory (GV) oocytes, ovulated oocytes in
      metaphase II (MII) and 1-cell parthenotes were fused with zygotes and the hybrid
      cells inseminated at various intervals after fusion. Sperm penetration was
      assessed on the basis of the presence of Giemsa-positive sperm heads in the air
      dried preparations. The oolemma block to sperm penetration develops in all types
      of hybrids although at different speeds: it develops fast (2-3 h) in oolemma
      derived from MII oocytes and artificially activated eggs, and slowly in oolemma
      derived from GV oocytes. In the GV oocyte-zygote hybrids the time of formation of
      the block varied: while 50% of cells lost the ability to fuse with sperm by 2 h
      after fusion, in the remaining cells the block must have developed some time
      between 5 and 18 h after fusion. How these sperm-induced modifications of the
      oolemma of fertilised egg spread in the hybrid cell and render the 'virgin' part
      of oolemma resistant to sperm penetration remains unknown.

PMID- 9921641
TI  - p-Aminobenzamidine-sensitive acrosomal protease(s) other than acrosin serve the
      sperm penetration of the egg zona pellucida in mouse.
AB  - It has been reported that a significant delay in protein dispersal from the
      acrosomal matrix is observed in wild-type sperm by adding p-aminobenzamidine, a
      trypsin/acrosin inhibitor, to the incubation medium. The pattern of this delayed
      release was similar to that of the acrosin-deficient mutant mouse sperm (Yamagata
      et al., J. Biol. Chem., 273, 10470-4, 1998). In the present study, no further
      delay in protein dispersal was found when the acrosin-deficient sperm were
      treated with p-aminobenzamidine, indicating that among the p-aminobenzamidine
      sensitive protease(s) only acrosin may function to accelerate this process.
      Although the acrosin-deficient sperm penetrated the zona pellucida (Baba et al.,
      J. Biol. Chem., 269, 31845-9, 1994), the addition of p-aminobenzamidine to the
      fertilisation medium caused a significant inhibition of fertilisation in vitro.
      This indicates that there is a p-aminobenzamidine-sensitive protease(s) other
      than acrosin participating in the zona penetration step. Indeed, we demonstrated
      that a non-acrosin protease with a size of 42 kDa was present in the supernatant
      of the acrosome-reacted sperm suspension. The enzyme was inhibited by p
      aminobenzamidine, diisopropyl fluorophosphate and N alpha-tosyl-L-lysine
      chloromethyl ketone, and was apparently activated by acrosin.

PMID- 9921643
TI  - Immunological characterisation of the acrosomal filament in the marine shrimp
      Sicyonia ingentis.
AB  - During sperm/egg interaction, the sperm of Sicyonia ingentis undergoes a unique
      biphasic acrosome reaction. After acrosomal vesicle exocytosis, the sperm
      generates an acrosomal filament, over a period of 4-6 min, that is approximately
      10 microns in length. Neither actin filaments nor normal microtubules have been
      demonstrated at the ultrastructural level of this unusual filament. Using a
      battery of cytoskeleton-directed antibodies the biochemical nature of this
      filament has been investigated. Antibodies to actin and tubulin do not label the
      subacrosome or acrosomal filament, but do recognise actin and tubulin in other
      shrimp tissues. Antibodies to tau, MAP2, and neurofilament medium and heavy
      subunits were all localised to the subacrosomal region of the sperm. It is
      interesting, however, that only the two clones of neurofilament monoclonal
      antibodies recognised the acrosomal filament. Electrophoretic and Western blot
      analysis in conjunction with amino acid sequencing revealed that the proteins
      localised to the acrosomal filament are of a unique sequence and may represent a
      new type of protein of centrosomal origin.

PMID- 9921644
TI  - Fertilisability and developmental ability of mouse oocytes with reduced amounts
      of cytoplasm.
AB  - To determine the minimal amount of cytoplasm necessary to support normal
      development of mouse oocytes, mature unfertilised oocytes were reduced in size
      into approximately 1/2, 1/4 and 1/8 by removing the cytoplasm, then inseminated.
      More than 80% of 1/2-size oocyte were fertilised normally and almost all
      fertilised eggs developed to blastocysts. When transferred to foster females, 31%
      of the blastocysts developed into normal offspring. In contrast, 1/4- and 1/8
      size oocytes, although they were penetrable by spermatozoa and extruded the
      second polar bodies, could not reach the 2-cell stage. In these oocytes, sperm
      nuclei did not develop into full-sized pronuclei. These results suggest that an
      oocyte can develop to full term after losing about half its cytoplasm, but not
      more.

PMID- 9921645
TI  - Detection of prothymosin alpha in oocytes and embryos of Bufo arenarum.
AB  - Prothymosin alpha (PTA) was detected by immunocytological and biochemical methods
      in oocytes at different stages of oogenesis, and in early embryos of the
      amphibian Bufo anenarum. In all cases PTA was detected in the nucleus and was
      absent from the cytoplasm. This indicates that this protein could act at the
      level of regulating transcription. Western blots were carried out using
      polyclonal antibodies with extracts of embryos at different stages of development
      from early fertilisation up to neural tube. With this method PTA was detected in
      all the samples under study.

PMID- 9921646
TI  - The influence of demethylating agents on preimplantation development of mice.
AB  - The effects of two demethylating drugs with a different mechanism of action (5
      azacytidine (Aza) and L-ethionine (Eth)) on mouse preimplantation development
      were investigated. Preimplantation embryos were cultured for 24 h in the presence
      of the drug and for an additional 24 or 48 h (depending on the cleavage stage) in
      medium supplemented with bromodeoxyuridine to reveal sister chromatid exchanges
      (SCEs) and the number of cell cycles performed before harvesting. Striking
      differences between the two drugs were observed in their influence on
      proliferation of blastomeres, primary differentiation and sister chromatid
      differentiation (SCD), and in the pattern of DNA methylation and the frequency of
      SCEs per cell. At a final concentration of 1 microM Aza had no effects, whereas
      higher concentrations stopped development of all stages except the zygote. In
      contrast Eth treatments (5 mM) resulted in a severe reduction of the mean cell
      number per embryo in comparison with controls. Moreover both the absence of
      blastocyst formation and no effects on mitotic activity were detected. The most
      prominent effect of Eth was detected at the zygote and 4-cell stages. An
      unexpected decrease in SCE frequency in Eth-treated morulae and 4-cell embryos
      has been observed. Data are explained taking into account the different
      mechanisms of action of the agents.

PMID- 9921647
TI  - Aberrant expression and dysfunction of Fas antigen in MRL/MpJ-lpr/lpr murine
      ovary.
AB  - In lpr mice the insertion of an early transposable element (ETn) into intron 2 of
      the Fas gene, which mediates apoptosis, causes the development of massive
      lymphadenopathy, splenomegaly and autoimmune disease. In the present study we
      investigated the influence of this mutation on ovarian development of lpr mice.
      By means of in situ hybridisation, the expression of Fas mRNA was detected at the
      same levels in the ovarian cells of MRL/MpJ-lpr/lpr (MRL/lpr) mice as in those of
      MRL/MpJ-(+)/+ (MRL/+) mice. However, indirect immunofluorescence (IIF) staining
      with anti-Fas monoclonal antibody (mAb) on the membrane of follicle and egg of
      MRL/lpr mice was significantly weaker than that of MRL/+ mice. Furthermore, the
      expression level of Fas protein at the 45 kDa band from ovarian cell lysates of
      MRL/lpr mice was much lower than that of MRL/+ mice. The co-incubation of
      Spodoptera frugiperda (Sf9)-Fas lig- and (L) cells with eggs of MRL/+ mice
      resulted in apoptosis of eggs, as detected by the terminal deoxynucleotide
      transferase mediated dUPT-nick end labelled (TUNEL) method. In contrast the co
      incubation of Sf9-FasL cells with eggs of MRL/lpr mice did not generate apoptosis
      in eggs. Following intraperitoneal administration of anti-Fas mAb into both types
      of mice, most oocytes, a proportion of granulosa cells in the ovary and
      hepatocytes in liver of MRL/+ mice were positively stained by the TUNEL method,
      corresponding to the appearance of DNA fragmented ladders by DNA fragmentation
      assay, while negative signals were obtained in those cells of MRL/lpr mice. As
      the mice aged, the ovarian size of MRL/lpr mice was found to be much larger than
      that of MRL/+ mice due to the increased number of ovarian follicles. Therefore,
      the ovarian adenopathy in MRL/lpr mice was strongly suggested to be caused by the
      dysfunction of Fas antigen in the ovary.

PMID- 9921648
TI  - Reliability of delta-crystallin as a marker for studies of chick lens induction.
AB  - Induction of a lens by the optic vesicle of the brain was the first demonstration
      of how tissue interactions could influence cell fate during development. However,
      recent work with amphibians has shown that the optic vesicle is not the primary
      inducer of lens formation. Rather, an earlier interaction between anterior neural
      plate and presumptive lens ectoderm appears to direct lens formation. One problem
      with many early experiments was the absence of an unambiguous assay for lens
      formation. Before being able to test whether the revised model of lens induction
      applies to chicken embryos, we examined the suitability of using delta-crystallin
      as a marker of lens formation. Although delta-crystallin is the major protein
      synthesized in the chick lens, one or both of the two delta-crystallin genes
      found in chickens is transcribed in many non-lens tissues as well. In studies of
      lens formation where appearance of the delta-crystallin protein is used as a
      positive assay, synthesis of delta-crystallin outside of the lens could make
      experiments difficult to interpret. Therefore, polyacrylamide gel
      electrophoresis, immunoblotting, and immunofluorescence were used to determine
      whether the delta-crystallin messenger RNA detected in non-lens tissues is
      translated into protein, as it is in the lens. On Coomassie-blue-stained gels of
      several tissues from stage-22 embryos, a prominent protein was observed that co
      migrated with delta-crystallin. However, on immunoblots, none of the nonlens
      tissues tested contained detectable levels of delta-crystallin at this stage. By
      imunofluorescence, delta-crystallin was observed in Rathke's pouch and in a large
      area of oral ectoderm near Rathke's pouch, yet none of the cells in these non
      lens tissues showed the typical elongated morphology of lens fiber cells. When
      presumptive lens ectoderm or other regions of ectoderm from stage-10 embryos were
      cultured and tested for lens differentiation, both cell elongation and delta
      crystallin synthesis were observed, or neither were observed. The results suggest
      that delta-crystallin synthesis and cell elongation together serve as useful
      criteria for assessing a positive lens response.

PMID- 9921649
TI  - The murine Cdx1 gene product localises to the proliferative compartment in the
      developing and regenerating intestinal epithelium.
AB  - The mouse Cdx1 gene encodes a homeobox-containing transcription factor and is one
      of the few homeobox genes known to be expressed in endodermally derived tissues
      of the intestine in fetal and adult mice. A detailed and systematic study of the
      expression of the Cdx1 protein was carried out during embryonic intestinal
      development, postnatal cytodifferentiation and in the regenerating (after
      radiation-induced damage) intestine of the mouse. Using antibodies directed
      against Cdx1, we show for the first time that the Cdx1 protein is localised in
      the proliferating immature epithelium during intestinal development. It becomes
      restricted to the proliferative crypt compartment during postnatal
      differentiation, as well as in the adult intestine. The mesenchymal layer was
      completely negative both during embryonic development and in the postnatal
      intestine. The expression of the protein was first clearly detected throughout
      the simple columnar epithelium at day 15 of development. This expression
      progressively became restricted to the regions of epithelial proliferation in the
      crypts of the adult mouse by day 40 of post-natal development. There were
      occasional cells that were Cdx1 positive in the villi. During regeneration of the
      epithelium after radiation-induced damage, Cdx1 expression diminished during the
      initial phase of cellular regression. The expression was then very strong in the
      regenerating epithelial foci, but not in the quiescent sterilised crypts between
      day 4 and 6. The normal pattern was restored between day 6 and 7. The Paneth
      cells were negative. The physical segregation of Cdx1 with the proliferative
      compartment and the hierarchy of cell renewal in the intestinal epithelium is an
      important example of how regulatory genes function in the maintenance and in the
      dysfunction of renewing tissues.

PMID- 9921650
TI  - Identification of two distinct functions for TGF-beta in early mouse development.
AB  - In this study the function of transforming growth factor-beta (TGF-beta) in
      preimplantation mouse embryos was examined. By RT-PCR, mRNA for the signalling
      type I (T beta R-I) and type II (T beta R-II) receptors for TGF-beta was shown to
      be present in two distinct time windows: in fertilized oocytes and at the
      blastocyst stage. The function of TGF-beta at these times was analysed in two
      ways. Firstly, the TGF-beta signalling pathway was blocked by injecting a DNA
      construct encoding a truncated T beta R-II, that acts as a dominant-negative
      receptor, in fertilized oocytes, and the effect on development was determined.
      Secondly, inner cell masses isolated at the blastocyst stage were cultured in
      vitro with and without TGF-beta under conditions that favour the outgrowth of
      parietal endoderm. The results show that TGF-beta signalling mediated by
      maternally expressed receptors is important for development of preimplantation
      embryos beyond the two-cell stage, and suggest a regulatory role for TGF-beta in
      the outgrowth of parietal endoderm.

PMID- 9921651
TI  - Increased expression of the LAZ3 (BCL6) proto-oncogene accompanies murine
      skeletal myogenesis.
AB  - The structural alterations of the LAZ3 (BCL6) gene are one of the most frequent
      events found in non-Hodgkin lymphoma. LAZ3 encodes a transcriptional repressor
      with a POZ/zinc finger structure similar to several Drosophila development
      regulators and to the human promyelocytic leukemia-associated PLZF gene.
      Consistent with the origin of LAZ3-associated malignancies, LAZ3 is expressed in
      mature B-cells and required for germinal center formation. However, its
      ubiquitous expression, with predominant levels in skeletal muscle, suggests that
      it may act outside the lymphoid system. To study how LAZ3 could be involved in
      skeletal muscle differentiation, we examined its expression in the C2 muscle
      cells. We report here that LAZ3 is upregulated at both mRNA and protein levels
      during the differentiation of proliferating C2 myoblasts into post-mitotic
      myotubes. This rise in LAZ3 expression is both precocious and sustained, and is
      not reversed when myotubes are re-exposed to mitogen-rich medium, suggesting that
      irreversible evens occurring upon myogenic terminal differentiation contribute to
      lock LAZ3 upregulation. In addition, using two different models, we found that a
      "simple" growth-arrest upon serum starvation is not sufficient to induce LAZ3
      upregulation which rather appears as a feature of myogenic commitment and/or
      differentiation. Finally, BrdU incorporation assays in C2 cells entering the
      differentiation pathway indicate that "high" LAZ3 expression strongly correlates
      with their exit from the cell cycle. Taken as a whole, these findings suggest
      that LAZ3 could play a role in muscle differentiation. Together with some results
      reported in other cell types, we propose that LAZ3 may contribute to events
      common to various differentiation processes, possibly the induction and
      stabilization of the withdrawal from the cell cycle.

PMID- 9921653
TI  - Maturation of peroxisomes in differentiating human hepatoblastoma cells (HepG2):
      possible involvement of the peroxisome proliferator-activated receptor alpha
      (PPAR alpha).
AB  - We have studied the alterations of peroxisomes in the human hepatoblastoma cell
      line HepG2, induced to differentiate by long-term cultivation (20 days without
      passaging) using morphological and biochemical techniques as well as mRNA
      analysis. Ultrastructural studies revealed alterations in shape and size of
      peroxisomes, with significant increases in mean diameter and formation of small
      clusters exhibiting heterogeneous staining for catalase after 20 days in culture.
      These alterations of peroxisomes correspond to the changes described during the
      maturation process from prenatal to adult human hepatocytes. As revealed by
      Northern and Western blotting there was marked elevation of the mRNA (190%) and
      protein (180%) of the peroxisomal branched-chain acyl-CoA oxidase. This protein
      is the key regulatory enzyme for the side chain oxidation of cholesterol for bile
      acid synthesis, a pathway associated with mature hepatocytes. Concomitantly a
      marked increase of bile canaliculi was noted by light and electron microscopy.
      This differentiation process was confirmed also by the increase of albumin
      synthesis (mRNA: 160%; protein: 190%) which is generally used as a
      differentiation marker of hepatocytes in culture. Interestingly, the mRNA for
      peroxisome proliferator-activated receptor alpha (PPAR alpha) increased
      drastically by almost 390% and its corresponding protein by 150%, suggesting its
      involvement in maturation of the peroxisomal compartment in differentiating HepG2
      cells. In contrast to the wellknown increases during the drug-induced peroxisome
      proliferation of cytochrome P450 4A, multifunctional enzyme 1, palmitoyl-CoA
      oxidase and the 70-kDa peroxisomal membrane protein, those proteins were either
      not altered or only slightly elevated during the differentiation process,
      suggesting that peroxisome proliferation and maturation are two distinct and
      differentially regulated processes.

PMID- 9921652
TI  - Cultured human sole-derived keratinocyte grafts re-express site-specific
      differentiation after transplantation.
AB  - Cultured epithelial autografts (CEA) derived from sole skin were transplanted to
      full-thickness wounds excised to muscle fascia over a variety of diverse body
      sites in 12 pediatric patients treated for acute burns or giant congenital nevi.
      The skin regenerated from the grafts was biopsied from 7 days to 6 years after
      grafting. The resultant epidermal phenotype was analyzed histologically and by
      immunohistochemical localization of keratin 9 (K9) as objective evidence of sole
      type site-specific differentiation. Expression of K9 was also verified by one
      dimensional gel electrophoresis of epidermal cytoskeletal extracts and K9
      immunoblot analysis. Grafts prepared from epidermis of axilla; groin or foreskin
      and transplanted to wounds of comparable depth in an identical manner in the same
      patients served as controls of postgrafting differentiation. Biopsies of sole
      skin from amputation specimens from patients of comparable age served as normal
      positive controls, and biopsies of nonsole skin from patients of comparable age
      served as normal negative controls. As early as 2 weeks postgrafting, the
      histologic appearance of sole-derived CEA differed substantively from that of
      axilla- or groin-derived CEA controls and displayed a phenotype characteristic of
      sole skin with a thick compact stratum corneum, a thick stratum granulosum, and a
      distinct stratum lucidum. In sole-derived grafts rete ridges regenerated within 2
      months postgrafting, whereas nonsole-derived grafts required 4-6 months for rete
      ridge regeneration. Once acquired, the sole skin phenotype was maintained long
      term by all sole-derived CEA. In vitro, sole-derived keratinocytes synthesized
      little, if any, K9. However, within 7 days after grafting, K9 synthesis by
      multiple suprabasal keratinocytes was seen within the epidermis regenerated from
      sole-derived CEA. Protein of K9 appeared progressively more diffuse throughout
      the suprabasal layers, attaining a confluent pattern of expression comparable to
      normal controls of sole skin by 6 to 12 months postgrafting, and the confluent
      pattern of suprabasal K9 synthesis was maintained long-term. The results
      demonstrate that site-specific differentiation is an intrinsic property of
      postnatal human keratinocytes and can be expressed and maintained in a permissive
      environment in the absence of dermal tissue.

PMID- 9921654
TI  - Multivariable feedback active structural acoustic control using adaptive
      piezoelectric sensoriactuators.
AB  - An experimental implementation of a multivariable feedback active structural
      acoustic control system is demonstrated on a piezostructure plate with pinned
      boundary conditions. Four adaptive piezoelectric sensoriactuators provide an
      array of truly colocated actuator/sensor pairs to be used as control transducers.
      Radiation filters are developed based on the self- and mutual-radiation
      efficiencies of the structure and are included into the performance cost of an H2
      control law which minimizes total radiated sound power. In the cost function,
      control effort is balanced with reductions in radiated sound power. A similarity
      transform which produces generalized velocity states that are required as inputs
      to the radiation filters is presented. Up to 15 dB of attenuation in radiated
      sound power was observed at the resonant frequencies of the piezostructure.

PMID- 9921656
TI  - Contralateral suppression of transiently evoked otoacoustic emissions by harmonic
      complex tones in humans.
AB  - Variations in the amplitude of transiently evoked otoacoustic emissions (TEOAEs)
      produced by a contralateral complex tone were measured in 26 normal-hearing human
      subjects. TEOAEs were evoked using a 1-kHz tone pip at 60 dB SPL. The
      contralateral complex consisted of harmonic components with frequencies between
      400 and 2000 Hz; it was presented at levels ranging from 40 to 50 dB SL and its
      fundamental frequency (F0) was varied. In experiment 1, the dependence of TEOAE
      amplitude variations on the F0 of the contralateral complex was measured by
      varying the F0 from 50 to 400 Hz in octave steps. The results revealed a
      nonmonotonic dependence of TEOAE amplitude variations on contralateral F0, with
      significantly larger TEOAE suppression for F0's of 100 and 200 Hz than for F0's
      of 50 and 400 Hz. Experiment 2, in which the harmonics were summed in alternating
      sine-cosine phase instead of constant sine phase, showed a shift of the function
      relating TEOAE attenuation to F0 towards lower F0's, indicating that the waveform
      repetition rate, rather than harmonic spacing, was the actual factor of the
      dependence of contralateral TEOAE attenuation on F0. Furthermore, significantly
      smaller suppression was observed with the alternating-phase complexes than with
      the sine-phase complexes, suggesting an influence of the waveform crest factor.
      Experiment 3 showed no difference between the contralateral TEOAE attenuation
      effects produced by positive and negative Schroeder-phase complexes. Overall,
      these results bring further arguments for the notion that contralaterally induced
      medial olivocochlear bundle (MOCB) activity, as measured through the
      contralateral suppression of TEOAEs in humans, is sensitive to the rate of
      temporal envelope fluctuations of the contralateral stimulus, with preferential
      rates around 100-200 Hz.

PMID- 9921655
TI  - Experimental confirmation of the two-source interference model for the fine
      structure of distortion product otoacoustic emissions.
AB  - High-resolution measurements of distortion product otoacoustic emissions (DPOAEs)
      from three different experimental paradigms are shown to be in agreement with the
      implications of a realistic "two-source" cochlear model of DPOAE fine structure.
      The measurements of DPOAE amplitude and phase imply an interference phenomenon
      involving one source in the region of strong nonlinear interaction of the primary
      waves (the strong "overlap" or generation region), and the other source region
      around the DPOAE tonotopic place. The component from the DPOAE place can be
      larger than the one from the generator region. These findings are supported by
      the analysis of the onset and offset of the DPOAE when the higher-frequency
      primary is pulsed on and off. The two-source hypothesis was further tested by
      adding a third tone closer in frequency to the DPOAE which modifies the amplitude
      of the component from the DPOAE place and leaves the one from the generator
      region unchanged. The results agree well with the model prediction that the
      variation with frequency, and implied latency, of the phase of the DPOAE
      tonotopic-place component are greater than the corresponding quantities for the
      component from the generation region.

PMID- 9921657
TI  - Do click-evoked otoacoustic emissions have frequency specificity?
AB  - Whether click-evoked otoacoustic emissions (CEOAEs) have frequency specificity is
      an issue still subject to debate. In order to resolve this issue, changes in the
      frequency components of the CEOAE power spectrum, together with changes in
      compound action potential (CAP) thresholds before and after pure-tone exposure in
      guinea pigs, were examined. Changes in CAP thresholds immediately before and 1 h
      after exposure were compared with changes in the frequency components in the
      CEOAE power spectrum before and 1 h after exposure. The ILO 88 was used for
      measurement of CEOAEs. Total echo energy in the CEOAE power spectrum was
      converted into frequency bands of 1000 Hz. Shifts in filtered echo power (FEP)
      levels correlated maximally with those in CAP thresholds at 0.5 kHz above the
      same frequency. Stepwise regression indicated that only one step could be entered
      in a linear regression model using the variable of CAP threshold shifts at 0.5
      kHz above the same frequency for all FEP shifts except FEP4.5. The remaining
      variables played a negligible role, since variance no longer changed when they
      were included in the regression equation. From these results, it was concluded
      that CEOAEs display frequency specificity. Influence on CEOAEs from higher
      frequencies is negligible.

PMID- 9921658
TI  - Discriminability of vowel representations in cat auditory-nerve fibers after
      acoustic trauma.
AB  - This paper attempts to connect deficits seen in the neural representation of
      speech with perceptual deficits. Responses of auditory-nerve fibers were studied
      in cats exposed to acoustic trauma. Four synthetic steady-state vowels were used
      as test signals; these stimuli are identical, except that the second format (F2)
      resonator in the synthesizer was set to 1.4, 1.5, 1.7, or 2 kHz, producing four
      spectra that differ mainly in the vicinity of the F2 frequency. These stimuli
      were presented to a large population (523) of auditory-nerve fibers in four cats
      with sloping high-frequency threshold shifts that reached 50-70 dB at 2-4 kHz. In
      normal animals, May et al. [Auditory Neurosci 3, 135-162 (1996)] showed
      previously that the discharge rates of fibers with best frequencies near the F2
      frequencies provide enough information to allow discrimination of these stimuli
      at the performance levels shown by cats in behavioral experiments. Here it is
      shown that, after acoustic trauma, there is essentially no rate information which
      would allow the vowels with different F2 frequencies to be discriminated.
      However, information that could allow discrimination remains in the temporal
      (phase-locked) aspects of the responses.

PMID- 9921659
TI  - Psychophysical measures of auditory nonlinearities as a function of frequency in
      individuals with normal hearing.
AB  - In order to gain a better understanding of how auditory nonlinear phenomena vary
      as a function of location along the cochlea, several psychophysical measures of
      nonlinearity were examined as a function of signal frequency. Six normal-hearing
      individuals completed three experiments, each designed to measure one aspect of
      nonlinear behavior: (1) the effects of level on frequency selectivity in
      simultaneous masking, measured using notched-noise maskers at spectrum levels of
      30 and 50 dB, (2) two-tone suppression, measured using forward maskers at the
      signal frequency (fs) and suppressor tones above fs, and (3) growth of masking,
      measured using forward maskers below fs at a signal/masker frequency ratio of
      1.44. Four signal frequencies (375, 750, 1500, and 3000 Hz) were tested to sample
      the nonlinear behavior at different locations along the basilar membrane, in
      order to test the hypothesis that the apical (low-frequency) region of the
      cochlea behaves more linearly than the basal (high-frequency) region. In general,
      all three measures revealed a progressive increase in nonlinear behavior as
      signal frequency increased, with little or no nonlinearity at the lowest
      frequency, consistent with the hypothesis.

PMID- 9921660
TI  - Sequential stream segregation in the absence of spectral cues.
AB  - This paper investigates the cues used by the auditory system in the perceptual
      organization of sequential sounds. In particular, the ability to organize sounds
      in the absence of spectral cues is studied. In the first experiment listeners
      were presented with a tone sequence ABA ABA ..., where the fundamental frequency
      (f0) of tone A was fixed at 100 Hz and the f0 difference between tones A and B
      varied across trials between 1 and 11 semitones. Three spectral conditions were
      tested: pure tones, harmonic complexes filtered with a bandpass region between
      500 and 2000 Hz, and harmonic complexes filtered with a bandpass region chosen so
      that only harmonics above the tenth would be passed by the filter, thus severely
      limiting spectral information. Listeners generally reported that they could
      segregate tones A and B into two separate perceptual streams when the f0 interval
      exceeded about four semitones. This was true for all conditions. The second
      experiment showed that most listeners were better able to recognize a short
      atonal melody interleaved with random distracting tones when the distracting
      tones were in an f0 region 11 semitones higher than the melody than when the
      distracting tones were in the same f0 region. The results were similar for both
      pure tones and complex tones comprising only high, unresolved harmonics. The
      results from both experiments show that spectral separation is not a necessary
      condition for perceptual stream segregation. This suggests that models of stream
      segregation that are based solely on spectral properties may require some
      revision.

PMID- 9921661
TI  - Dual temporal pitch percepts from acoustic and electric amplitude-modulated pulse
      trains.
AB  - Two experiments examined the perception of unmodulated and amplitude-modulated
      pulse trains by normally hearing listeners and cochlear implantees. Four normally
      hearing subjects listened to acoustic pulse trains, which were band-pass filtered
      between 3.9 and 5.3 kHz. Four cochlear implantees, all postlinguistically deaf
      users of the Mini System 22 implant, listened to current pulse trains produced at
      a single electrode position. In the first experiment, a set of nine loudness
      balanced unmodulated stimuli with rates between 60 and 300 Hz were presented in a
      multidimensional scaling task. The resultant stimulus spaces for both subject
      groups showed a single dimension associated with the rate of the stimuli. In the
      second experiment, a set of ten loudness-balanced modulated stimuli was
      constructed, with carrier rates between 140 and 300 Hz, and modulation rates
      between 60 and 150 Hz. The modulation rates were integer submultiples of the
      carrier rates, and each modulation period consisted of one higher-intensity pulse
      and one or more identical lower-intensity pulses. The modulation depth of each
      stimulus was adjusted so that its pitch was judged to be higher or lower 50% of
      the time than that of an unmodulated pulse train having a rate equal to the
      geometric mean of the carrier and modulation rates. A multidimensional scaling
      task with these ten stimuli resulted in two-dimensional stimulus spaces, with
      dimensions corresponding to carrier and modulation rates. A further investigation
      with one normally hearing subject showed that the perceptual weighting of the two
      dimensions varied systematically with modulation depth. It was concluded that,
      when filtered appropriately, acoustic pulse trains can be used to produce
      percepts in normal listeners that share common features with those experienced by
      subjects listening through one channel of a cochlear implant, and that the
      central auditory system can extract two temporal patterns arising from the same
      cochlear location.

PMID- 9921662
TI  - Effect of temporal position, proportional variance, and proportional duration on
      decision weights in temporal pattern discrimination.
AB  - Two experiments investigated how listeners allocate their attention to different
      segments of a temporal pattern. The experiments allowed a direct test of the
      predictions of the Proportion of Total Duration (PTD) rule and the Component
      Relative Entropy (CoRE) model. Listeners had to decide whether two sequences of
      nine tones had the same or different temporal patterns (tone duration = 25 ms,
      tone frequency = 1000 Hz). A sequence's temporal pattern was determined by the
      time intervals between each tone's offset and the next tone's onset. On same
      trials, the time intervals at corresponding temporal positions in the two
      sequences were identical. On different trials, the corresponding time intervals
      were randomly varied. Listener attention to different temporal positions within a
      sequence was assessed by calculating the decision weights at each position. The
      results supported the CoRE model and were inconsistent with the PTD rule.
      Manipulating the mean of the time intervals within the sequence had no consistent
      effect on the pattern of weights (or on overall performance), indicating that
      listener attention was not affected by either the proportion of total duration or
      the perceptual salience of a longer or shorter time interval. However,
      manipulating the variance of the time intervals had a significant effect: the
      highest weight was given to the highest variance segment. This weighting strategy
      leads to better performance because higher variance segments are more diagnostic
      of whether the sequences are the same or different.

PMID- 9921663
TI  - Lateralization of a moving auditory image: interrelation of interaural time and
      intensity differences.
AB  - Lateralization of moving fused auditory images (FAIs) was studied under dichotic
      stimulation, with FAI movement from the right and left ears to midline. The
      movement was produced by the gradual change of interaural time delay (from +/-
      630 to 0 microseconds) in a binaurally presented click train in which a constant
      interaural intensity difference (IID) between +/- 13 dB was also imposed. The
      task of the subjects was to show with her/his finger the point on the head
      surface where the FAI trajectory's ending or starting points were perceived. With
      IID change within +/- 13 dB, the FAI movement trajectory shifted toward the ear
      receiving the more intense stimulus. The length of the movement trajectory
      shortened with IID increase. Functions relating the value of perceived lateral
      position (Y) of the movement trajectory's ending and starting points to IID value
      (X) were nearly linear: Y = AX + B. These functions differed in their
      characteristics whether the movement was to the right versus to the left of
      midline. They also differed from analogous functions for stationary FAI. At IID =
      0 the FAI movement trajectory's endpoint was shifted from midline in the
      direction of movement. Equivalence ratio for IID and ITD were estimated to be 51
      and 29 microseconds/dB respectively for the trajectory's starting and ending
      points. The IID factor could be several times as effective in moving FAI
      lateralization as the ITD factor.

PMID- 9921664
TI  - Observer weighting of interaural delays in source and echo clicks.
AB  - A correlational analysis was used to assess the relative weight given to the
      interaural differences of time (IDTs) of source and echo clicks for echo delays
      ranging from 1-256 ms. In three different experimental conditions, listeners were
      instructed to discriminate the IDT of the source, the IDT of the echo, or the
      difference between the IDTs of the source and echo. The IDT of the target click
      was chosen randomly and independently from trial-to-trial from a Gaussian
      distribution (mu = 0 microsecond, sigma = 100 microseconds). The IDT of the
      nontarget click was either fixed at 0 microsecond or varied in the same manner as
      the IDT of the target. The data show that for echo delays of 8 ms or less,
      greater weight was given to the IDT of the source than to that of the echo in all
      experimental conditions. For echo delays from 16-64 ms, the IDT of the echo was
      weighted slightly more than that of the source and the weights accounted for a
      greater proportion of the responses when the echo was the target, indicating that
      the binaural information in the echo was dominant over the binaural information
      in the source. The data suggested the possibility that for echo delays from 8-32
      ms, listeners were unable to resolve the temporal order of the source and echo
      IDTs. Listeners were able to weight the binaural information in the source and
      echo appropriately for a given task only when the echo delay was 128 ms or
      greater.

PMID- 9921665
TI  - Masking with interaurally delayed stimuli: the use of "internal" delays in
      binaural detection.
AB  - Detectability of 500-Hz tones was measured in the presence of broadband masking
      noise using three types of binaural conditions. In the first, the masker was
      presented diotically and the tone was interaurally delayed. In the second, the
      masker was interaurally delayed and the 500-Hz tone was presented either in phase
      (S0) or out of phase (S pi). In the third, the masker consisted of the sum of two
      independent noises having interaural delays of equal magnitude and opposite sign.
      The signal was, once more, presented either in phase (S0) or out of phase (S pi).
      Comparisons among the data and quantitative analyses assuming the use of
      compensatory "internal delays" suggested that internal delays are operative and
      compensate accurately for external delays of up to approximately 750
      microseconds. The analyses also indicated that larger internal delays (i.e., up
      to 2 to 3 ms) are probably also operative. However, performance using such large
      internal delays appears to be degraded in accord with the hypothesis that their
      application introduces "noise" in the internal representation of the stimuli.

PMID- 9921666
TI  - Benefits of linear amplification and multichannel compression for speech
      comprehension in backgrounds with spectral and temporal dips.
AB  - People with cochlear hearing loss have markedly higher speech-receptions
      thresholds (SRTs) than normal for speech presented in background sounds with
      spectral and/or temporal dips. This article examines the extent to which SRTs can
      be improved by linear amplification with appropriate frequency-response shaping,
      and by fast-acting wide-dynamic-range compression amplification with one, two,
      four, or eight channels. Eighteen elderly subjects with moderate to severe
      hearing loss were tested. SRTs for sentences were measured for four background
      sounds, presented at a nominal level (prior to amplification) of 65 dB SPL: (1) A
      single female talker, digitally filtered so that the long-term average spectrum
      matched that of the target speech; (2) a noise with the same average spectrum as
      the target speech, but with the temporal envelope of the single talker; (3) a
      noise with the same overall spectral shape as the target speech, but filtered so
      as to have 4 equivalent-rectangular-bandwidth (ERB) wide spectral notches at
      several frequencies; (4) a noise with both spectral and temporal dips obtained by
      applying the temporal envelope of a single talker to speech-shaped noise [as in
      (2)] and then filtering that noise [as in (3)]. Mean SRTs were 5-6 dB lower
      (better) in all of the conditions with amplification than for unaided listening.
      SRTs were significantly lower for the systems with one-, four-, and eight-channel
      compression than for linear amplification, although the benefit, averaged across
      subjects, was typically only 0.5 to 0.9 dB. The lowest mean SRT (-9.9 dB,
      expressed as a speech-to-background ratio) was obtained for noise (4) and the
      system with eight-channel compression. This is about 6 dB worse than for elderly
      subjects with near-normal hearing, when tested without amplification. It is
      concluded that amplification, and especially fast-acting compression
      amplification, can improve the ability to understand speech in background sounds
      with spectral and temporal dips, but it does not restore performance to normal.

PMID- 9921667
TI  - Subjective effects of peak clipping and compression limiting in normal and
      hearing-impaired children and adults.
AB  - Despite many advances in hearing-aid signal processing, compression limiting and
      peak clipping are still used. To date, perceptual studies have been conducted
      only with adults. The current study was designed to investigate the clarity of
      peak-clipped and compressed speech for both adults and children. Subjects were 30
      normal-hearing and 30 hearing-impaired individuals in three age ranges (7-9, 10
      12, and 16-50 years). Stimuli were processed at 60, 70, 75, and 80 dB SPL using
      peak clipping and at 80 dB SPL using compression limiting. Paired-comparison
      measures were used to assess the clarity of sentences, and a signal-to-distortion
      ratio (SDR) based on a measure of coherence between input and output was computed
      for each condition. For the peak-clipping conditions, there was a decrease in
      perceived clarity as the input increased from 60 to 80 dB SPL. This perceptual
      continuum was most apparent for the normal-hearing adults. The normal-hearing 10
      12 year olds and the hearing-impaired adults showed a similar, but less
      pronounced, pattern. In contrast, the remaining three subject groups showed
      minimal differences in perceived clarity across conditions. Surprisingly, only
      the two oldest normal-hearing groups showed a clear preference for compression
      limiting over peak clipping at the highest input level, and only their results
      were consistent with the pattern of coherence across stimuli. Judgments of
      clarity by the normal-hearing subjects correlated best with the SDR in the 500
      2000-Hz range, while clarity judgments of the hearing-impaired subjects
      correlated best with the SDR below 1000 Hz.

PMID- 9921668
TI  - A theoretical study of the hysteresis phenomenon at vocal fold oscillation onset
      offset.
AB  - This paper presents a theoretical study on the differences in the biomechanical
      parameters of the vocal folds between oscillation onset and offset. The dynamics
      of the oscillation is analyzed from the perspective of the theory of nonlinear
      dynamical systems, using a mucosal wave model of the vocal folds with the
      subglottal pressure and the vocal fold half-width as control parameters. It is
      shown that the oscillation onset occurs through a Hopf bifurcation of the
      subcritical type, at which an unstable limit cycle is generated. Also, the
      oscillation offset occurs at a cyclic fold bifurcation, at which the unstable
      limit cycle and a stable limit cycle (the actual vocal fold oscillation) coalesce
      and cancel each other. Both bifurcations combine to form an "oscillation
      hysteresis" phenomenon, common in cases of flow-induced oscillations. An
      analytical expression for the onset/offset ratio of parameters is derived. The
      onset/offset ratio is in the range of 0.5-1, in agreement with the experimental
      evidence. This value depends on the phase delay in motion of the upper edge of
      the vocal folds versus the lower edge, and on the particular model adopted for
      airflow separation within the glottis.

PMID- 9921669
TI  - Global and local dimensions of vocal dynamics.
AB  - The global embedding dimension (dE) and the local dynamical dimension (dL) are
      calculated from the microphone and electroglottographic (EGG) signals elicited
      from five healthy subjects and seven dysphonic subjects with laryngeal pathology
      during phonation of sustained/a/. The data from each pathologic subject contain
      at least one bifurcation and are divided into periodic and irregular segments for
      analysis. The dE values from both the microphone and EGG signals elicited from
      the healthy subjects indicate that a relatively small coordinate space can be
      used to reconstruct the attractor, with little residual noise. Consistent across
      all healthy subjects, three dominant degrees of freedom (dL) are found to govern
      local dynamics of the trajectories on the attractor. From the pathologic
      subjects, many of the dE values suggest the presence of a high-dimensional
      component in the signals. However, the noise does not completely obscure the
      deterministic dynamics of the source signal or prevent extraction of an optimal
      global embedding dimension. The data do not reveal consistent differences in
      degrees of freedom between healthy and pathologic phonation, or between different
      modes of pathologic phonation. However, the dL values suggest that the pathologic
      vocal fold vibration of these subjects, even highly irregular vibration, is
      governed locally by a low number of dominant degrees of freedom, sometimes no
      greater than those calculated from the signals of healthy subjects. Only in the
      cases of severe breathiness are the microphone and EGG signals sufficiently
      contaminated by noise to obscure any deterministic component.

PMID- 9921670
TI  - The impact of early onset otitis media on babbling and early language
      development.
AB  - Numerous studies have shown that otitis media (OM) during infancy has a negative
      impact on language development later in life. Few studies have examined the
      effect of OM on linguistic and prelinguistic behavior during infancy. The purpose
      of this study was to investigate the impact of OM on the development of canonical
      babble in children who experienced at least one episode during the period birth
      through 6 months of age, in comparison with children who did not experience OM
      during this period. The results show a consistently lower rate of canonical
      syllable production among children with early onset OM, when compared to children
      with later onset OM, during the period 6 through 18 months of age. In addition, a
      relationship between canonical babbling ability and expressive vocabulary size
      was observed at 18 months of age.

PMID- 9921671
TI  - Some lengthening factors in English speech combine additively at most rates.
AB  - The known lengthening effects of phrase-final position and of contrastive
      emphasis have been predicted by Klatt to combine superadditively. In a new
      experiment, texts elicited at a wide range of speaking rates were measured and
      the separate and combined effects of these lengthening factors were found to
      combine approximately additively at all rates studied. The proportion of
      lengthening attributable to each factor was found to be relatively invariant
      except at the fastest speaking rates, where lengthening was eventually
      eliminated. The results support the interpretation of absolute speaking rate as
      an inessential variable for characterizing speech at a range of moderate rates.

PMID- 9921672
TI  - Utterance rate and linguistic properties as determinants of lexical dysfluencies
      in children who stutter.
AB  - Two important determinants of variation in stuttering frequency are utterance
      rate and the linguistic properties of the words being spoken. Little is known how
      these determinants interrelate. It is hypothesized that those linguistic factors
      that lead to change in word duration, alter utterance rate locally within an
      utterance that then gives rise to an increase in stuttering frequency. According
      to the hypothesis, utterance rate variation should occur locally within the
      linguistic segments in an utterance that is known to increase the likelihood of
      stuttering. The hypothesis is tested using length of tone unit as the linguistic
      factor. Three predictions are confirmed: Utterance rate varies locally within the
      tone units and this local variation affects stuttering frequency; stuttering
      frequency is positively related to the length of tone units; variations in
      utterance rate are correlated with tone unit length. Alternative theoretical
      formulations of these findings are considered.

PMID- 9921673
TI  - Neuronal response to cochlear distortion products in the anteroventral cochlear
      nucleus of the gerbil.
AB  - To receive information on the intracochlear magnitude and propagation properties
      of cochlear distortion products, the neuronal response of AVCN cells to
      distortion stimuli and the acoustical correlates in the ear canal (DPOAE) were
      measured for frequencies between 0.7 and 45.3 kHz. Comparison of the growth of
      neuronal response to a distortion stimulus and the neuronal rate-versus-level
      function for an externally applied pure tone of equal frequency allowed for an
      assessment of the intracochlear magnitude of the distortions. AVCN neurons with a
      characteristic frequency (CF) > 1.8 kHz started to respond to the intracochlear
      distortion stimulus, at primary levels for which the ear-canal level of the
      corresponding DPOAE was close to the pure-tone threshold of the units. This
      finding suggests that transmission of sound energy is comparable in the forward
      and reverse direction, and that mechanical distortions of the cochlea are fully
      encoded by neurons in the AVCN. For neurons with a CF < 1.8 kHz, the
      intracochlear magnitude of the distortion stimulus appeared to be about 15 to 30
      dB higher than the corresponding DPOAE, at the threshold of neuronal response.
      This discrepancy between intracochlear magnitude of cochlear distortions and
      their acoustical expression may be explained by high-pass filter action of the
      middle ear during DPOAE re-emission from the cochlea. A contribution to the
      observed discrepancy of the type of distortion (cubic versus quadratic) used as
      stimulus, and possible differences in mechanical frequency processing between the
      apex and base of the gerbil cochlea, are also discussed. The delay of the
      neuronal response to an intracochlear distortion stimulus was on average 1.1 ms
      longer than the neuronal delay to an external pure tone of equal frequency and
      intensity, most likely stemming from the activation delay of the DPOAE generating
      mechanisms.

PMID- 9921674
TI  - Language identification with suprasegmental cues: a study based on speech
      resynthesis.
AB  - This paper proposes a new experimental paradigm to explore the discriminability
      of languages, a question which is crucial to the child born in a bilingual
      environment. This paradigm employs the speech resynthesis technique, enabling the
      experimenter to preserve or degrade acoustic cues such as phonotactics, syllabic
      rhythm, or intonation from natural utterances. English and Japanese sentences
      were resynthesized, preserving broad phonotactics, rhythm, and intonation
      (condition 1), rhythm and intonation (condition 2), intonation only (condition
      3), or rhythm only (condition 4). The findings support the notion that syllabic
      rhythm is a necessary and sufficient cue for French adult subjects to
      discriminate English from Japanese sentences. The results are consistent with
      previous research using low-pass filtered speech, as well as with phonological
      theories predicting rhythmic differences between languages. Thus, the new
      methodology proposed appears to be well suited to study language discrimination.
      Applications for other domains of psycholinguistic research and for automatic
      language identification are considered.

PMID- 9921675
TI  - Psychoacoustical evaluation of PSOLA. II. Double-formant stimuli and the role of
      vocal perturbation.
AB  - This article presents the results of listening experiments and psychoacoustical
      modeling aimed at evaluating the pitch synchronous overlap-and-add (PSOLA)
      technique. This technique can be used for simultaneous modification of pitch and
      duration of natural speech, using simple and efficient time-domain operations on
      the speech waveform. The first set of experiments tested the ability of subjects
      to discriminate double-formant stimuli, modified in fundamental frequency using
      PSOLA, from unmodified stimuli. Of the potential auditory discrimination cues
      induced by PSOLA, cues from the first formant were found to generally dominate
      discrimination performance. In the second set of experiments the influence of
      vocal perturbation, i.e., jitter and shimmer, on discriminability of PSOLA
      modified single-formant stimuli was determined. The data show that
      discriminability deteriorates at most modestly in the presence of jitter and
      shimmer. With the exception of a few conditions, the trends in these data could
      be replicated by either using a modulation-discrimination or an intensity
      discrimination model, dependent on the formant frequency. As a baseline
      experiment detection thresholds for jitter and shimmer were measured. Thresholds
      for jitter could be replicated by using either the modulation-discrimination or
      the intensity-discrimination model, dependent on the (mean) fundamental frequency
      of stimuli. The thresholds for shimmer could be accurately predicted for stimuli
      with a 250-Hz fundamental, but less accurately in the case of a 100-Hz
      fundamental.

PMID- 9921676
TI  - Additivity of perceptual channel-crossing effects in auditory gap detection.

PMID- 9921677
TI  - The origin of the Australasian marsupial fauna and the phylogenetic affinities of
      the enigmatic monito del monte and marsupial mole.
AB  - Alternative hypotheses in higher-level marsupial systematics have different
      implications for marsupial origins, character evolution, and biogeography.
      Resolving the position of the South American monito del monte (Order
      Microbiotheria) is of particular importance in that alternate hypotheses posit
      sister-group relationships between microbiotheres and taxa with disparate
      temporal and geographic distributions: pediomyids; didelphids; dasyuromorphians;
      diprotodontians; all other australidelphians; and all other marsupials. Among
      Australasian marsupials, the placement of bandicoots is critical; competing views
      associate bandicoots with particular Australasian taxa (diprotodontians,
      dasyuromorphians) or outside of a clade that includes all other Australasian
      forms and microbiotheres. Affinities of the marsupial mole are also unclear. The
      mole is placed in its own order (Notoryctemorphia) and sister-group relationships
      have been postulated between it and each of the other Australasian orders. We
      investigated relationships among marsupial orders by using a data set that
      included mitochondrial and nuclear genes. Phylogenetic analyses provide support
      for the association of microbiotheres with Australasian marsupials and an
      association of the marsupial mole with dasyuromorphs. Statistical tests reject
      the association of diprotodontians and bandicoots together as well as the
      monophyly of Australasian marsupials. The origin of the paraphyletic Australasian
      marsupial fauna may be accounted for by (i) multiple entries of australidelphians
      into Australia or (ii) bidirectional dispersal of australidelphians between
      Antarctica and Australia.

PMID- 9921678
TI  - Molecular evidence for genetic subdivision of Antarctic krill (Euphausia superba
      Dana) populations.
AB  - Antarctic krill (Euphausia superba Dana) is a key species in the Antarctic food
      web and occurs on a circumcontinental scale. Population genetic structure of this
      species was investigated by sequence analysis of the ND1 mitochondrial gene in
      four population samples collected at different geographical localities around the
      Antarctic continent. Results indicate the existence of significant genetic
      differences between samples, and we suggest that oceanographic barriers could be
      sufficiently strong and temporally stable to restrict gene flow between distinct
      areas. Moreover, our data indicate that Antarctic krill is not at mutation-drift
      equilibrium and that the species possibly has a low effective population size as
      compared to the census size.

PMID- 9921679
TI  - Phylogeny of Wolbachia in filarial nematodes.
AB  - Intracellular bacteria have been observed in various species of filarial
      nematodes (family Onchocercidae). The intracellular bacterium of the canine
      filaria Dirofilaria immitis has been shown to be closely related to Wolbachia, a
      rickettsia-like micro-organism that is widespread among arthropods. However, the
      relationships between endosymbionts of different filariae, and between these and
      the arthropod wolbachiae, appear not to have been studied. To address these
      issues we have examined ten species of filarial nematodes for the presence of
      Wolbachia. For nine species, all samples examined were PCR positive using primers
      specific for the ftsZ gene of Wolbachia. For one species, the examined samples
      were PCR negative. Sequences of the amplified ftsZ gene fragments of filarial
      wolbachiae fall into two clusters (C and D), which are distinct from the A and B
      clusters recognized for arthropod wolbachiae. These four lineages (A-D) are
      related in a star-like phylogeny, with higher nucleotide divergence observed
      between C and D wolbachiae than that observed between A and B wolbachiae. In
      addition, within each of the two lineages of filarial wolbachiae, the phylogeny
      of the symbionts is consistent with the host phylogeny. Thus, there is no
      evidence for recent Wolbachia transmission between arthropods and nematodes.
      Endosymbiont 16S ribosomal DNA sequences from a subset of filarial species
      support these findings.

PMID- 9921680
TI  - Natural selection on age-specific fertilities in human females: comparison of
      individual-level fitness measures.
AB  - Lifetime reproductive success and timing of reproduction are key components of
      life-history evolution. To understand the evolution of reproductive schedules, it
      is important to use a measure of fitness that is sensitive both to reproductive
      quantity and reproductive timing. There is a contradiction between the theory,
      which mainly focuses on the rate measures of fitness (r and lambda), and
      empirical studies, which mainly use lifetime reproductive success (LRS), or some
      of its correlates, as a fitness measure. We measured phenotypic selection on age
      specific fertilities in three pre-modern human populations using individually
      estimated finite rate of increase, er (lambda). We found that lambda and lifetime
      reproductive success ranked individuals differently according to their fitness:
      for example, a female giving birth to four children at a young age may actually
      have a higher fitness than a female giving birth to six children at a greater
      age. Increase in fertility at the young age classes (15-19 years) was favoured by
      selection, but the intensity of selection on fertility was higher in the older
      age classes (20-30 years), where the variance in fertility was highest. Hence,
      variation in fertility in the older age classes (20-30) was actually responsible
      for most of the observed variation in fitness among the individuals.
      Additionally, more than 90% of variation in fitness (lambda) was attributable to
      individual differences in LRS, whereas only about 5% of all variation in fitness
      was due to differences in the reproductive schedule. The rate-sensitive fitness
      measure did not significantly challenge the importance of total fertility as a
      component of fitness in humans. However, the rate-sensitive measure clearly
      allowed more accurate estimation of individual fitness, which may be important
      for answering some more specific questions.

PMID- 9921681
TI  - The geographical spread of influenza.
AB  - How infectious diseases spread in space within one cycle of an epidemic is an
      important question that has received considerable theoretical attention. There
      are, however, few empirical studies to support theoretical approaches, because
      data are scarce. Weekly reports obtained since 1984 from a network of general
      practitioners spanning the entire French territory allows the analysis of the
      spatio-temporal dynamics of influenza over a fine spatial scale. This analysis
      indicates that diffusion over long distances, possibly due to global
      transportation systems, is so quick that homogeneous global mixing occurs before
      the epidemic builds up within infected patches. A simple model in which the total
      number of cases is given by the empirical time-series and cases are randomly
      assigned to patches according to the population weight of the patches exhibits
      the same spatio-temporal properties as real epidemic cycles: homogeneous mixing
      models constitute appropriate descriptions, except in the vicinity of the
      epidemic's peak, where geographic heterogeneities play a role.

PMID- 9921683
TI  - Separate colour-opponent mechanisms underlie the detection and discrimination of
      moving chromatic targets.
AB  - Current opinion holds that human colour vision is mediated primarily via a colour
      opponent pathway that carries information about both wavelength and luminance
      contrast (type I). However, some authors argue that chromatic sensitivity may be
      limited by a different geniculostriate pathway, which carries information about
      wavelength alone (type II). We provide psychophysical evidence that both pathways
      may contribute to the perception of moving, chromatic targets in humans,
      depending on the nature of the visual discrimination. In experiment 1, we show
      that adaptation to drifting, red-green stimuli causes reductions in contrast
      sensitivity for both the detection and direction discrimination of moving
      chromatic targets. Importantly, the effects of adaptation are not directionally
      specific. In experiment 2, we show that adaptation to luminance gratings results
      in reduced sensitivity for the direction discrimination, but not the detection of
      moving chromatic targets. We suggest that sensitivity for the direction
      discrimination of chromatic targets is limited by a colour-opponent pathway that
      also conveys luminance-contrast information, whereas the detection of such
      targets is limited by a pathway with access to colour information alone. The
      properties of these pathways are consistent with the known properties of type-I
      and type-II neurons of the primate parvocellular lateral geniculate nucleus and
      their cortical projections. These findings may explain the known differences
      between detection and direction discrimination thresholds for chromatic targets
      moving at low to moderate velocities.

PMID- 9921682
TI  - Human brain activity during spontaneously reversing perception of ambiguous
      figures.
AB  - Looking at ambiguous figures results in rivalry with spontaneous alternation
      between two percepts. Using event-related functional magnetic resonance imaging,
      we localized transient human brain activity changes during perceptual reversals.
      Activation occurred in ventral occipital and intraparietal higher-order visual
      areas, deactivation in primary visual cortex and the pulvinar. Thus, without any
      physical stimulus changes, salient perceptual flips briefly engage widely
      separated specialized cortical areas, but are also associated with intermittent
      activity breakdown in structures putatively maintaining perceptual stability.
      Together, the dynamics of integrative perceptual experience are reflected in
      rapid spatially differentiated activity modulation within a cooperative set of
      neural structures.

PMID- 9921685
TI  - An on-line preconcentrator and the evaluation of electrospray interfaces for the
      capillary electrophoresis/mass spectrometry of peptides.
AB  - A unique preconcentrator was constructed for on-line preconcentration using
      capillary electrophoresis generating concentration detection limits for peptides
      in the mid-picomolar range. Several common sheathless electrospray configurations
      were constructed in conjunction with the preconcentrator and were compared. It
      was found that a palladium wire interface was the most reliable interface and the
      problems encountered using this interface are discussed. A tryptic digest of the
      myosin I heavy chain kinase that contains two phosphopeptides was separated by
      capillary electrophoresis using this interface and the on-line preconcentrator.

PMID- 9921684
TI  - Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in
      Great Britain.
AB  - Understanding the epidemiology and aetiology of new-variant Creutzfeldt-Jakob
      (vCJD) disease in humans has become increasingly important given the scientific
      evidence linking it to bovine spongiform encephalopathy (BSE) in cattle and hence
      the wide exposure of the population of Great Britain (GB) to potentially
      infectious tissue. The recent analysis undertaken to determine the risk to the
      population from dorsal route ganglia illustrated the danger in presenting point
      estimates rather than ranges of scenarios in the face of uncertainty. We present
      a mathematical template that relates the past pattern of the BSE epidemic in
      cattle to the future course of any vCJD epidemic in humans, and use extensive
      scenario analysis to explore the wide range of possible outcomes given the
      uncertainty in epidemiological determinants. We demonstrate that the average
      number of humans infected by one infectious bovine and the incubation period
      distribution are the two epidemiological factors that have the greatest impact on
      epidemic size and duration. Using the time-series of the BSE epidemic and the
      cases seen to date, we show that the minimum length of the incubation period is
      approximately nine years, and that at least 20% of the cases diagnosed to date
      were exposed prior to 1986. We also demonstrate that the current age distribution
      of vCJD cases can only arise if younger people were either exposed to a greater
      extent, more susceptible to infection, or have shorter incubation periods.
      Extensive scenario analyses show that given the information currently available,
      the very high degree of uncertainty in the future size of the epidemic will
      remain for the next 3-5 years. Furthermore, we demonstrate that this uncertainty
      is unlikely to be reduced by mass screening for late-stage infection.

PMID- 9921686
TI  - Direct evaluation of glycated and glyco-oxidized globins by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) has
      been applied to achieve a qualitative and quantitative evaluation of glycated
      globins on a wide number of healthy and diabetic subjects. The method allowed us
      to establish that both alpha- and beta-globins are glycated and that, in addition
      to simply glycated products, other species are detected. Investigations by
      different sample treatments and by analysis of the glycated beta-globin fraction
      obtained by preparative chromatography indicated that these species correspond to
      glyco-oxidized globins. Consequently MALDI-MS can be validly employed to evaluate
      not only the glycation level, but also the degree of oxidative stress. The
      percentages of glycated and glycooxidized species were calculated from the
      related MALDI spectra by the measurement of the related peak areas, without any
      other treatment of data. A linear relationship between HbA1c values and the total
      percentage of glycated and glyco-oxidized globins has been found, and its slope
      (< 1) has been rationalized by the uncorrected evaluation of glycated globins
      content in the standard samples employed for HbA1c measurements.

PMID- 9921688
TI  - Liquid chromatography/microspray mass spectrometry for bacterial investigations.
AB  - Cellular proteins (biomarkers) specific to any individual microorganism,
      determined by the direct mass spectral analysis of the corresponding intact
      cellular suspension, can be applied for the rapid and specific identification of
      the organisms present in unknown samples. The components of the bacterial
      suspensions, after a rapid separation over a C18 reversed-phase microcapillary
      column, were directly subjected to on-line electrospray ionization followed by
      analysis using an ion trap tandem mass spectrometer. This approach is equally
      effective for gram-positive as well as gram-negative bacteria but has a distinct
      advantage over our earlier reported method involving matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). During
      electrospray ionitation mass spectrometry (ESI-MS), liquid samples can be
      directly analyzed and there is the potential for developing tandem mass spectral
      methods for more specific identification of the individual organisms present in
      crude bacterial mixtures. The total analysis time leading to unambiguous
      bacterial identification in samples was less than 10 minutes and the results were
      quite reproducible. Miniaturization of the instrumentation along with total
      automation of this simple process could have immense impact on field operations.
      Routine, rapid, cost-effective field monitoring of environmental samples,
      agricultural products, samples from food processing, industrial sites and health
      institutions for suspected bacterial contamination could be a reality in the near
      future. Potential utility in biological, medical, bioprocessing, pharmaceutical,
      and other industrial research is also enormous.

PMID- 9921689
TI  - Magnetic sector-ion trap mass spectrometry with electrospray ionization for high
      sensitivity peptide sequencing.
AB  - A hybrid mass spectrometer composed of a high resolution double focusing
      instrument (electrostatic analyzer-magnetic sector, EB) and an ion trap analyzer
      (T) exhibits high sensitivity performance for peptide sequencing with
      electrospray ionization (ESI). MS2 and MS3 experiments for multiply charged
      tryptic peptides and larger peptides (e.g., melittin, 2.8 kDa) generate sequence
      informative product ions. Collisionally activated dissociation (CAD) of selected
      precursor ions can also be performed in the interface between the double focusing
      analyzer and the ion trap (transfer octapole region) to generate product ions.
      With a low-flow micro-ESI source, which can deliver analyte solution to the
      source at a flowrate of 10-200 nL/min, tandem mass spectra can be obtained from
      sub-fmol amounts of melittin. The high resolving power of the MS-I stage combined
      with the efficiency of the ion trap stage allows for high resolution precursor
      ion selection with subsequent highly sensitive tandem mass spectrometry (MS/MS)
      analysis.

PMID- 9921690
TI  - A novel nanospray capillary zone electrophoresis/mass spectrometry interface.
AB  - The high resolution of capillary zone electrophoresis/mass spectrometry (CZE/MS)
      offers a promising technique to characterize biomolecules in pharmaceutical and
      biotechnology industries. A novel capillary zone electrophoresis/electrospray
      ionization time-of-flight mass spectrometry (CZE/ESI-TOFMS) interface was
      designed in this study to successfully integrate ESI-TOFMS, nanospray, and CZE
      for biomolecular identification. The interface offers a novel way to take
      advantage of the high resolution separation achieved during CZE and the detection
      sensitivity of nanospray ESI-MS. The results showed mixtures of peptides were
      highly resolved within a few minutes (each CZE electropherogram of a peptide is 2
      3 seconds). The novel CZE/ESI-TOFMS interface may simultaneously provide
      sensitivity, data acquisition speed, mass range, and mass resolution while
      maintaining resolution of the CZE separation.

PMID- 9921691
TI  - Detection and identification of low-mass peptides and proteins from solvent
      suspensions of Escherichia coli by high performance liquid chromatography
      fractionation and matrix-assisted laser desorption/ionization mass spectrometry.
AB  - The application of high performance liquid chromatography (HPLC) to separate
      components in solvent suspension of Escherichia coli followed by off-line matrix
      assisted laser desorption/ionization (MALDI) analysis of collected fractions
      results in the detection of over 300 peaks in the 2000-19,000 Da mass range, an
      order of magnitude increase in the number of components observed when compared
      with direct MALDI analysis of the entire solvent suspension. Mass measurements of
      these separated components using a time-lag focusing MALDI instrument are
      reported. MALDI analysis of the proteolytic digests of several collected
      fractions facilitates the identification of three components as specific proteins
      expected to be present in E. coli. The methodologies reported here should be very
      useful in searching for unique biomarkers for bacterial discrimination.

PMID- 9921692
TI  - (NH4)8[Ce2(SO4)8].4H2O.
AB  - Crystals of the title compound, octaammonium dicerium octasulfate tetrahydrate,
      suitable for X-ray work, were prepared by a hydrothermal reaction. The structure
      is made up of [Ce2(SO4)8]8- anions, interacting with the crystallization waters
      and the NH4+ cations through hydrogen bonds. The CeIV atom in the [Ce2(SO4)8]8-
      anion is ninefold coordinated by O atoms belonging to sulfate groups. The
      coordination polyhedron is a somewhat distorted tricapped trigonal prism. The Ce
      O distances range from 2.325(2) to 2.478(2) A.

PMID- 9921693
TI  - Quinoline-4-carboxylic acid.
AB  - The title acid, C10H7NO2, crystallized in the centrosymmetric space group P2(1)/c
      with one molecule in the asymmetric unit. There is a single hydrogen bond. O
      H...N, with a donor-acceptor distance of 2.596 (1) A. The carboxylic H atom is
      ordered. The dihedral angle between the best-fit quinoline core plane and the
      carboxyl plane is 45.9 (1) degrees. Structural comparisons are made with the
      closely related molecule 2-phenylquinoline-4-carboxylic acid.

PMID- 9921694
TI  - 1-(o-tolylmethyl)naphthalene-2-carboxylic acid.
AB  - The title acid, C19H16O2, crystallized in space group P1. In this structure, a
      hydrogen bond of the 'cyclic dimer' type is formed about a center of symmetry.
      The O(donor)...O(acceptor) distance is 2.647 (1) A. The carboxylic H and O atoms
      are ordered. The dihedral angle between the best-fit naphthalene plane and the
      carboxylic acid group plane is 11.1 (2) degrees.

PMID- 9921695
TI  - Hydrogen-bonded trimers in 4,4'-dimethylbiphenyl-2,2'-dicarboxylic acid.
AB  - The title acid, C16H14O4, crystallized in the centrosymmetric space group C2/c
      with 1.5 molecules in the asymmetric unit. Each of the three independent
      carboxylic H atoms is ordered, and each participates in hydrogen bonding. The
      OD...OA distances in the hydrogen bonds are 2.584 (2), 2.647 (2) and 2.722 (2) A.
      Three sets of cyclic dimer hydrogen bonds are formed within and between two
      asymmetric units, linking them into molecular trimers. The trimers lie on twofold
      axes which bisect the central C-C bond of one molecule and the COOH dimer
      connecting the other two. The two biphenyl twist angles are 68.1 (1) and 64.6 (1)
      degrees. The dihedral angles between the benzene-ring planes and the planes of
      the carboxyl groups attached to them are 0.7 (3), 23.3 (2) and 18.4 (2) degrees.
      Structural comparisons are made with the 'parent' compound, diphenic acid, and
      with the isomeric compound, 6,6'-dimethylbiphenyl-2,2'-dicarboxylic acid.

PMID- 9921696
TI  - 9H-fluorene-2-carboxaldehyde.
AB  - The title compound, C14H10O, crystallized in the centrosymmetric space group
      P2(1)/c with a single molecule in the asymmetric unit. The C-H...O interaction
      having the shortest C...O distance involves the ring-bridging C9 atom and one of
      its H atoms, and results in the formation of a cyclic dimer about a center of
      symmetry. The molecular core is nearly planar. The dihedral angle between the
      best-fit plane of the ring to which the aldehyde group is attached and the plane
      of the aldehyde group is 4.4 (9) degrees. In a number of respects the molecular
      disposition is similar to that previously determined for the geometrically
      similar dibenzofuran-4-carboxaldehyde molecule.

PMID- 9921697
TI  - Using secondary binding properties to select a not so selective serotonin
      reuptake inhibitor.

PMID- 9921698
TI  - Use of atypical neuroleptics in child and adolescent psychiatry.
AB  - BACKGROUND: This article reviews the published clinical experience with atypical
      neuroleptics in children and adolescents. METHOD: A computerized literature
      search was conducted (MEDLINE, 1974-1998) to retrieve all reports on the use of
      atypical neuroleptics in children and adolescents. A hand search was performed as
      well. All relevant clinical data were collated by type of drug. RESULTS: We found
      5 blind placebo-controlled clinical trials (105 patients), 24 open-label clinical
      trials (387 patients), and 33 case series (115 patients) describing the use of
      the atypical neuroleptics clozapine, risperidone, olanzapine, sulpiride,
      tiapride, amisulpride, remoxipride, and clothiapine in children and adolescents.
      Some of these agents, especially clozapine, risperidone, and olanzapine, were
      found to be efficacious in the treatment of schizophrenia, bipolar disorders, and
      pervasive developmental disorders. The role of atypical neuroleptics as
      augmenters of serotonin reuptake inhibitors in obsessive-compulsive disorder is
      unclear. Risperidone appears to possess anti-tic properties in patients with
      Tourette's disorder. CONCLUSION: The most convincing evidence of the efficacy of
      atypical neuroleptics in children and adolescents concerns clozapine in the
      treatment of schizophrenia. Data on other atypical neuroleptics in other
      disorders are still sparse, and further research is needed. Some of the atypical
      neuroleptics may become the first-line treatment for childhood schizophrenia and
      pervasive developmental disorders.

PMID- 9921699
TI  - Comparison of 2 treatment strategies for depressed inpatients: imipramine and
      lithium addition or mirtazapine and lithium addition.
AB  - BACKGROUND: The purpose of this study was to compare the overall effectiveness of
      2 treatment strategies for inpatients with severe major depressive episode (DSM
      III-R): (1) mirtazapine (phase 1) and subsequent lithium addition (phase 2) or
      (2) imipramine (phase 1) and subsequent lithium addition (phase 2). We previously
      reported the results of phase 1. METHOD: In phase 1, patients were randomly
      assigned to treatment with either mirtazapine or imipramine, and doses were
      adjusted to obtain predefined blood drug levels. Nonresponders had lithium added
      to the double-blind mirtazapine or imipramine medication. The dose was adjusted
      to obtain a blood lithium level of 0.5-1.0 mmol/L. Treatment effects were
      evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2
      weeks on this blood lithium level. RESULTS: Data for 100 patients were available
      for comparison of the 2 treatment strategies. 80 patients received no
      comedication. By the end of phase 2, 24 (48%) of 50 had responded to mirtazapine
      and 32 (64%) of 50 had responded to imipramine (intent-to-treat analysis). A
      survival analysis of the total patient group intent-to-treat showed a significant
      difference in favor of the treatment strategy with imipramine and subsequent
      lithium addition. CONCLUSION: Efficacy of imipramine and subsequent lithium
      addition for nonresponders is superior to the same treatment strategy with
      mirtazapine. This applies to the patient sample studied, which consisted of 100
      severely depressed inpatients, 29 of whom were psychotically depressed. More
      serious side effects of imipramine, however, led to discontinuation of imipramine
      in 5 patients. No serious side effects were observed during the phase of lithium
      addition to either imipramine or mirtazapine. We, therefore, prefer to start
      treatment with imipramine and test for fixed blood drug levels, and, if
      necessary, add lithium. In the case of prohibitive side effects, patients are
      switched to a modern antidepressant such as mirtazapine, and, if necessary,
      lithium is added to this antidepressant.

PMID- 9921700
TI  - A randomized, double-blind, placebo-controlled trial of buspirone in combination
      with an SSRI in patients with treatment-refractory depression.
AB  - BACKGROUND: Case reports and open studies have reported beneficial therapeutic
      effects of adding buspirone to a selective serotonin reuptake inhibitor (SSRI) in
      the management of treatment-refractory depression. This is the first placebo
      controlled study to evaluate the efficacy and safety of this combination. METHOD:
      One hundred nineteen patients (82 women, 37 men) who fulfilled criteria for a
      major depressive episode according to DSM-IV and who had failed to respond to a
      minimum of 4 weeks (mean = 211 days) of treatment with citalopram or paroxetine
      were randomly assigned to 4 weeks of treatment with an SSRI plus buspirone (N =
      58) or an SSRI plus placebo (N = 61). In addition, 97 patients participated in an
      optional open-label poststudy treatment phase with the SSRI plus buspirone for 2
      weeks. The primary outcome measure was the score on the Clinical Global
      Impressions-Improvement (CGI-I) scale. RESULTS: A total of 50.9% of patients in
      the buspirone group and 46.7% in the placebo group responded after 4 weeks of
      treatment. The difference in response rate was not statistically significant. No
      statistically significant differences were found in the frequency of adverse
      events. At the follow-up of the open SSRI plus buspirone treatment, 69.4% of
      patients had responded. CONCLUSION: Adding buspirone to an SSRI is a safe and
      well-tolerated drug regimen. This study failed to demonstrate any difference in
      efficacy between buspirone or placebo augmentation of an SSRI. It could be
      argued, however, that the study was inconclusive due to the unusually high
      placebo response.

PMID- 9921701
TI  - Predictors of response to acute treatment of chronic and double depression with
      sertraline or imipramine.
AB  - BACKGROUND: The literature on predictors of response to treatment of nonchronic
      major depression has identified shorter duration of illness, acute onset, and
      less severity of illness as positive predictors. Unfortunately, there are almost
      no data on predictors of response to treatment for chronic depression. This study
      examined predictors of response to pharmacotherapy (sertraline or imipramine) in
      the treatment of outpatients who had DSM-III-R-defined chronic major or double
      depression. METHOD: The acute phase of the Chronic Major Depression and Double
      Depression Study is a double-blind, randomized, parallel-group 12-week comparison
      of sertraline and imipramine. Analyses are based on 623 patients who comprised
      the intent-to-treat sample, of whom 299 were nonresponders and 324 were
      responders, defined by a priori criteria as either remission or satisfactory
      therapeutic response. A stepwise logistic multiple regression analysis was
      performed on candidate clinical, psychosocial, and demographic variables
      previously identified as statistically significant in an attempt to develop a
      predictive model of positive antidepressant response. RESULTS: The
      sociodemographic variables that were predictive of positive response included
      living with spouse or partner or being at least a high school graduate. With
      regard to symptomatology and clinical history, responders had significantly lower
      baseline depression severity scores. In general, comorbid anxiety, substance
      abuse, and personality disorders did not influence rates of response. However,
      the presence of depressive personality traits was associated with a higher
      nonresponse rate. Among psychosocial variables, longer duration of personal
      relationships as well as higher baseline quality of life were associated with
      positive response. A stepwise logistic multiple regression identified 5 variables
      living with spouse or partner, higher educational level, passive-aggressive
      personality, lower introverted-tense personality traits, and higher quality of
      life--that significantly and independently contributed to the predictive model.
      This model correctly classified 67% of patients. CONCLUSION: A higher baseline
      quality of life, living with spouse or partner, and having more education were
      the strongest predictors of response to acute pharmacotherapy among chronically
      depressed patients. Clinical variables and comorbidity were not identified as
      independent predictors, although personality traits did appear to influence
      treatment response. Overall, the predictive value of these baseline measures was
      modest, and therefore of limited clinical utility.

PMID- 9921702
TI  - Divalproex sodium for impulsive aggressive behavior in patients with personality
      disorder.
AB  - OBJECTIVE: Divalproex sodium, an anticonvulsant and antimanic agent, has recently
      been studied for its antiaggressive effects in patients with brain injuries,
      dementia, and borderline personality disorder. Since patients with other
      personality disorders also exhibit impulsive aggressive behavior, we conducted a
      preliminary open-label trial of divalproex sodium as a treatment for irritability
      and aggression in patients with a variety of personality disorders. METHOD: Ten
      patients meeting DSM-IV criteria for at least one personality disorder were
      treated with divalproex sodium in an 8-week open clinical trial. All patients had
      failed a trial of a selective serotonin reuptake inhibitor (SSRI). Divalproex
      sodium was increased as tolerated using a flexible dosing schedule. Clinician
      ratings for impulsive aggressive behavior and irritability were made every 2
      weeks using the modified Overt Aggression Scale (OAS-M). RESULTS: Six of 8
      completers reported significant decreases in irritability (p = .003) and
      impulsive aggressive behavior (p = .019). For the entire sample, improvement on
      OAS-M irritability and overt aggression scores was noted by the end of 4 weeks
      and continued to occur through week 8. CONCLUSION: This study suggests that
      divalproex sodium is an effective treatment for impulsive aggressive behavior in
      some patients with personality disorder who fail to respond to other
      antiaggressive agents (i.e., SSRIs). Controlled studies are needed to determine
      which patients are most likely to benefit from divalproex sodium and to evaluate
      the differential effectiveness of various agents in reducing impulsive aggressive
      behavior.

PMID- 9921703
TI  - Upper-extremity self-amputation and replantation: 2 case reports and a review of
      the literature.
AB  - BACKGROUND: Patients who deliberately amputate 1 or more of their own extremities
      present a unique set of challenges for the entire treatment team. Decisions
      regarding replantation of the amputated extremity must be made quickly, and the
      psychiatrist is involved early in the care of these difficult patients. Surgical
      staff may feel that replantation surgery is inappropriate for such patients,
      although there is limited literature addressing this issue. Therefore, the
      psychiatrist must also address the strong feelings that such patients generate in
      nonpsychiatric caregivers. METHOD: Two cases of deliberate upper-extremity self
      amputation are discussed, and the world literature on self-amputation and
      replantation from 1966 to the present, identified via a MEDLINE search, using the
      key words self-amputation, self-inflicted, upper extremity, and amputation, is
      reviewed. RESULTS: There have been 11 reported cases (plus 2 in the current
      report) of deliberate upper-extremity amputation in the last 30 years. All
      patients have been psychotic, and many of the case reports note that patients
      with this presentation are rarely suicidal. Instead, the amputation usually stems
      from psychotically driven feelings of guilt and concrete religious
      preoccupations. Patients who undergo replantation often are pleased with the
      reattachment, and both psychiatric and surgical outcomes appear to benefit from
      prompt and aggressive psychiatric treatment. CONCLUSION: Patients who
      deliberately amputate one or more of their extremities can be unsettling as well
      as challenging. The psychiatrist must coordinate diagnosis and treatment among
      multiple services to ensure the best possible outcome. As replantation surgery
      becomes more common, the psychiatric implications of surgical reattachment are of
      increasing importance. More cases need to be described to better understand the
      best treatment options for this particular patient population.

PMID- 9921704
TI  - Inaccurate information on quetiapine.

PMID- 9921705
TI  - Hyperglycemia associated with olanzapine.

PMID- 9921706
TI  - St. John's wort and hypomania.

PMID- 9921707
TI  - Edema associated with addition of risperidone to valproate treatment.

PMID- 9921708
TI  - Nefazodone for mood disorder associated with epilepsy.

PMID- 9921709
TI  - Behavioral treatment of chronic insomnia in psychiatrically ill patients.
AB  - BACKGROUND: Psychiatric patients often have residual intractable insomnia as a
      serious problem. METHOD: Forty-eight psychiatrically ill patients (DSM-IV
      diagnoses) who had failed to respond to medicinal treatment for chronic insomnia
      were referred for and completed behavioral therapy as an adjunct to the
      pharmacologic treatment of their insomnia. The behavioral treatments included
      structured sleep hygiene, progressive muscle relaxation, stimulus control, and
      sleep restriction. The treatment program was accomplished in 6 sessions over 2
      months. Follow-up evaluations were completed at 2, 6, and 12 months from the
      beginning of the treatment program. The outcome of the treatment program was
      evaluated in terms of the change in (1) self-reported specific sleep parameters,
      (2) self-ratings of sleep-related day-time state, (3) self-rating of quality of
      sleep, (4) the use of sleep medication, and (5) the therapist's global rating of
      improvement. RESULTS: There was a statistically significant change from the
      baseline in all self-reported specific sleep parameters after 2 months that was
      sustained after 6 and 12 months. Sleep-related characteristics of daytime state
      showed statistically significant changes after 2 and 6 months that were
      maintained after 12 months. Sleep quality had a statistically significant change
      after 2 months, continued to improve statistically after 6 months, and was
      maximum after 12 months. Over half the patients (52.7%; 20 of 38) either reduced
      their sleep medication by half or stopped it completely. The therapist's global
      rating showed an improvement in 29.2% (N = 14) of patients after 2 months, 56.2%
      (N = 27) after 6 months, and 68.7% (N = 33) after 12 months. CONCLUSION: The use
      of concomitant behavioral and pharmacologic treatment of chronic insomnia in
      psychiatrically ill patients results in improving sleep and sleep-related state
      and reduces the risk of return of insomnia for 10 months after finishing active
      treatment.

PMID- 9921710
TI  - Heat shock proteins: facts, thoughts, and dreams.
AB  - The most primitive mechanism of cellular protection involves the expression of a
      polypeptide family named heat shock or stress proteins (hsps). Some of these hsps
      are present in unstressed cells and play an important role in the folding and
      translocation of polypeptides across membranes. Thus, they have been termed
      molecular chaperones. Hsps are expressed in response to an array of stresses,
      including hyperthermia, oxygen radicals, heavy metals, ethanol, and amino acid
      analogues. In addition, the heat shock response is induced during clinically
      relevant situations such as ischemia/reperfusion and circulatory and hemorrhagic
      shock. All of the above stresses have in common that they disturb the tertiary
      structure of proteins and have adverse effects on cellular metabolism.
      Pretreatment of cells with a mild stress, sufficient to induce the expression of
      hsps, results in protection to subsequent insults. This phenomenon has been
      coined "stress tolerance" and is apparently caused by the resolubilization of
      proteins that were denatured during the stress. In addition, cellular structures
      (microfilaments and centrosomes) and processes (transcription, splicing, and
      translation) are stabilized or repaired during a second stress in stress tolerant
      cells and organisms. There is a great body of evidence indicating a direct role
      of hsps in the stabilization of these events. The intrinsic capacity of hsps to
      protect cells has potential relevance as a natural mechanism of organ protection
      during harmful environmental conditions and operative procedures, and in the
      combat against pathogens.

PMID- 9921711
TI  - Continuous heparinization and circulating adhesion molecules in the critically
      ill.
AB  - Endothelial activation and damage are common endpoints of a complex process that
      may result in multiple organ dysfunction syndrome (MODS). The influence of
      continuous intravenous heparinization on plasma levels of circulating adhesion
      molecules was studied in 28 trauma patients (injury severity score between 15 and
      25 points) and 28 sepsis patients secondary to abdominal surgery. According to a
      prospective, randomized sequence the patients received either unfractionated
      heparin (aim: activated partial thromboplastin time (aPTT) approximately 2 x
      normal) (trauma-heparin (n = 14); sepsis-heparin (n = 14)) or not (trauma (n =
      14); sepsis (n = 14)). Plasma levels of circulating soluble endothelial leukocyte
      adhesion molecule-1 (sELAM-1), vascular cell adhesion molecule-1 (sVCAM-1),
      intercellular adhesion molecule-1 (slCAM-1), and granule membrane protein-140
      (sGMP-140) were serially measured from arterial blood samples for 5 days.
      Approximately 600 U/h of heparin were given to increase aPTT to approximately 60
      s. Plasma levels of all adhesion molecules increased in all groups. This increase
      was significantly (p < .05) highest in both sepsis groups (sepsis: sELAM-1: from
      50+/-11 to 84+/-19 ng/mL; slCAM-1: 410+/-68 to 700+/-95 ng/mL), but did not
      differ significantly between the treated and nontreated patients (sepsis-heparin:
      sELAM-1: from 60+/-131 to 88+/-20 ng/mL; slCAM-1: from 398+/-99 to 686+/-119
      ng/mL). Trauma patients showed a less pronounced increase in all adhesion
      molecules without differences between the two subgroups. Only sGMP-140 increased
      significantly (p < .05) more in the trauma (from 102+/-20 to 169+/-16 ng/mL) than
      in the trauma-heparin group (from 109+/-19 to 132+/-17 ng/mL). It is summarized
      that continuous heparinization with approximately 600 U/h did not attenuate the
      rise in circulating adhesion molecules in sepsis and trauma patients. The study
      findings suggest that heparin in this dose regimen may be unlikely to influence
      endothelial inflammation or endothelial function in critically ill patients.

PMID- 9921712
TI  - A mechanism of TNFR type II (75 kDa) "shedding" in macrophages.
AB  - Adherent macrophage populations derived from monocytes isolated from peripheral
      blood were evaluated for their ability to "shed" the membrane-associated receptor
      for TNF-alpha (TNFR) following exposure to a calcium ionophor (A23187) and a
      synthetic chemotactic peptide (fMLP) reagent. A soluble fraction of TNFR was
      detected in "cell-free" supernatant produced by stimulated macrophage populations
      applying 125I-TNF-alpha and biotinylated TNF-alpha ligand-binding analysis (96
      well format) in combination with conventional autoradiographic techniques.
      Approximate molecular weight of the shed TNFR glycoprotein fraction was estimated
      to be 75 kDa based on interpretation of nondenaturing PAGE gels transferred
      laterally onto sheets of nitrocellulose membrane subsequently probed by ligand
      binding analysis applying 125I-TNF-alpha and biotinylated TNF-alpha as detection
      modalities. Immunorecognition techniques were also employed to detect TNFR
      fragments shed from macrophages using biotinylated anti-TNFR Type II (75 kDa)
      monoclonal antibody in combination with conjugated strepavidin:HRPO and a
      chemiluminescent substrate reagent. In an effort to identify the class of enzyme
      directly mediating TNFR Type II (75 kDa) shedding, a spectrum of carboxyl- (e.g.,
      aspartate), hydroxyl- (e.g., serine), thiol (e.g., cysteine), and metalo- (e.g.,
      Ca2+, Mg2+) protease-inhibiting agents were evaluated. Experimental findings
      implied that a carboxy (aspartate) peptidase, and possibly to a lesser extent,
      serine (hydroxyl), and thiol (cysteine) peptidases participate in macrophage TNFR
      Type II (75 kDa) shedding phenomena. Subsequent investigations demonstrated that
      the carboxy (aspartate) peptidase cathepsin-D promoted liberation of TNFR Type II
      (75 kDa) in unactivated populations of adherent macrophages. In an effort to
      complement these observations, a protein fraction with presumed carboxy
      (aspartate) protease activity was isolated from the cell-free supernatant
      generated by activated populations of adherent macrophages using immobilized
      pepstatin-A beaded agarose. Exposure of unstimulated populations of adherent
      macrophages to the partially purified pepstatin-A binding protein fractions
      resulted in the liberation of a soluble TNFR Type II (75 kDa) fragment based on
      interpretation of ligand-binding and immunorecognition analysis of samples
      developed by SDS-PAGE/PAGE format and transferred onto sheets of nitrocellulose
      membrane. The molecular weight of the macrophage pepstatin-A binding protein
      fraction was estimated to be 47-52 kDa with lesser bands also visible at
      approximately 26-32 kDa, and 100 kDa based on SDS-PAGE analysis. Nondenaturing
      hemoglobin-PAGE substrate gel analysis of protein fractions possessing pepstatin
      A binding-avidity detected a protease with a molecular weight of approximately 47
      52 kDa that proteolytically digested hemoglobin, in addition to a synthetic
      cathepsin-D specific peptide substrate. Collective interpretation of these
      experimental findings directly corresponds with many of the physical (molecular)
      and functional (biochemical) characteristics known to be associated with the
      leukocyte carboxy (aspartate) peptidase cathepsin-D, which is a non
      metaloprotease known to exert relatively limited proteolytic activity.

PMID- 9921713
TI  - Major burn trauma in rats promotes cardiac and gastrointestinal apoptosis.
AB  - The hypothesis that cardiac functional abnormalities that occur after major burn
      trauma are paralleled by an increased incidence of apoptosis in cardiac myocytes
      was examined. Adult Sprague-Dawley rats were given a full thickness scald burn
      comprising 43+/-1% of the total body surface area or were manipulated identically
      but not exposed to burn injury (sham burn); burned rats were fluid resuscitated
      with lactated Ringer's solution. Tissues from burn and sham burn animals were
      then examined by the TUNEL (TdT-mediated dUTP nick end labeling) assay and light
      microscopy to determine the presence of apoptosis 24 and 48 h after burn trauma.
      In parallel, the mechanical function of the heart was assayed in separate groups
      of rats. Tissues harvested from the hearts of sham-treated animals showed
      essentially no apoptosis, whereas a small number of apoptotic cells were noted in
      the intestinal villi and liver of sham-treated animals. Twenty-four hours after
      burn trauma, there was a marked increase in apoptotic cells in the left ventricle
      (+916%), and the number of apoptotic cells remained increased by eightfold 48 h
      postburn. Apoptosis was noted predominately in the subendocardial tissue of the
      left ventricle. The appearance of apoptotic cells was paralleled by a decrease in
      cardiac mechanical function with significant decreases in left ventricular
      pressure and +/-dP/dt(max). Burn injury also increased apoptosis in the small
      intestine significantly, whereas apoptosis in the liver did not increase with
      burn trauma. These data suggest that the apoptosis of the cardiac myocytes that
      occurs after burn trauma may contribute, in part, to postburn cardiac mechanical
      dysfunction.

PMID- 9921714
TI  - The effect of a tyrosine kinase inhibitor on endotoxin mortality and splenocyte
      mediator production in the neonatal rat.
AB  - Tyrosine kinases mediate cellular signal transduction to endotoxin. A class of
      tyrosine kinase inhibitors, the tyrphostins, have been shown to protect mice from
      endotoxin-induced lethality. Neonatal rats and mice have been shown to be
      uniquely susceptible to lethal endotoxic shock. In our study, the effect of a
      lipophilic tyrphostin, AG 556, on endotoxin-induced neonatal and adult mortality
      and in vitro neonatal splenic cell thromboxane (TxB2), tumor necrosis factor
      alpha (TNF-alpha), and nitric oxide (NO) production were examined. Neonatal rats
      (<24 h old) were administered tyrphostin (100 microg subcutaneous) 2 h before an
      approximate LD50 dose of Salmonella enteritidis endotoxin (.024
      mg/kg/intracardiac). There was a significant decrease in mortality in the animals
      pretreated with 100 microg of tyrphostin (29% mortality in the treated group, n =
      41 versus 53% in the vehicle control group, n = 40; p < .05). Also in adult rats
      tyrphostin (5 mg/kg intraperitoneal) 2 h before endotoxin (10 mg/kg intravenous)
      significantly improved survival (50% drug treated versus 84% in control, n =
      12/group; p < .05). Adherent neonatal splenic cell mediator production of TxB2,
      TNF-alpha, and NO (measured by nitrite) in tyrphostin pretreated splenic cells
      were compared with endotoxin-stimulated splenic cells in vitro. The studies (n =
      4) demonstrate an increase (p < .05) in the production of TxB2, TNF-alpha, and NO
      in the endotoxin- (10 microg/mL) stimulated adherent splenic cells compared with
      basal. Tyrphostin pretreatment (10, 20, 50 microM) produced a dose-dependent
      decrease (p < .05) in endotoxin-stimulated TxB2 and TNF-alpha production. NO
      production was not significantly reduced. In conclusion, tryphostin appears to
      have a protective effect on mortality in both adult and neonatal rat endotoxic
      shock. Tyrphostin decreased specific mediator production in stimulated neonatal
      cells. Thus, inhibition of signal transduction pathways of endotoxin activation
      by tyrosine kinase inhibition may provide an effective approach to treat
      endotoxic shock in the neonate.

PMID- 9921715
TI  - Alterations of G-protein and adenylate cyclase signaling in rat liver during the
      progression of sepsis.
AB  - Changes in the protein level of various subunits of G-protein and the activity of
      adenylate cyclase in rat liver plasma membranes during different metabolic phases
      of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP).
      The results show that the protein levels of Galphai-2 and Galphai-3 were
      unchanged during the early hypermetabolic (hyperglycemic) phase (9 h after CLP),
      whereas Galphaai-2 and Galphaai-3 were increased by 32.4 and 59.1%, respectively,
      during the late hypometabolic (hypoglycemic) phase (18 h after CLP) of sepsis.
      The protein levels of Galphas and Gbeta remained unaltered during both the early
      and the late phases of sepsis. The activity of adenylate cyclase remained
      unchanged during the early phase, whereas it was decreased by 26% (p < .05)
      during the late phase of sepsis. Since the G-protein/adenylate cyclase signaling
      system mediates hormonal control of hepatic glucose metabolism, the observed
      increases in the Galphai-2 and Galphai-3 protein levels coupled with a decrease
      in the activity of adenylate cyclase may contribute to the development of the
      hypoglycemia during the late stage of sepsis.

PMID- 9921716
TI  - Intestinal blood flow and intramucosal pH in experimental peritonitis.
AB  - BACKGROUND AND AIMS: Experimental peritonitis causes gut intramucosal acidosis
      indicating intramucosal ischemia. However, tissue acidosis may reflect other
      conditions than ischemia. An increased mucosal-arterial Pco2 difference ( Pco2
      gap) is suggested to be a more adequate measure of tissue ischemia than
      intramucosal pH (pHi). This study was performed to elucidate whether keeping
      cardiac index (CI) and splanchnic blood flow normal or supranormal by
      administration of colloids and an inotropic drug could prevent the acidosis as
      well as reduce the Pco2-gap. A secondary aim was to study to what degree the low
      pHi in peritonitis really reflects ischemia. SUBJECTS: 24 anesthetized pigs (18
      27 kg) divided into four groups. MODELS: A Swan-Ganz catheter, transonic flow
      meters and catheters for blood sampling were applied. pHi was calculated using
      tonometry. Standardized fecal peritonitis was induced, except in controls. One
      peritonitis group was given dextran (Group P(DEX)) and another in addition
      dobutamine (Group PDOB) to keep CI normal or supranormal, respectively. RESULTS:
      After 4 h, a significant drop in pHi was found in all peritonitis groups, most
      pronounced in untreated peritonitis (to 7.09+/-.02). Corresponding values in
      Group P(DEX) and Group P(DOB) were 7.22+/-.03 and 7.22+/-.01, respectively, and
      in controls 7.30+/-.02. The Pco2-gap and the mucosal-arterial [H+] difference
      ([H+]-gap) increased significantly in untreated peritonitis but did not increase
      in groups given dextran and dextran + dobutamine. CONCLUSION: Maintaining CI in
      peritonitis attenuated the reduction in pHi and prevented the increased Pco2- and
      [H+]-gap. It seems justified from these data to conclude that the somewhat
      reduced pHi in treated peritonitis groups did not reflect tissue ischemia.

PMID- 9921717
TI  - Influence of L-arginine, aminoguanidine, and NG-nitro-L-arginine methyl ester (L
      name) on the survival rate in a rat model of hemorrhagic shock.
AB  - Nitric oxide (NO) has been implicated in the pathophysiology of hemorrhagic
      shock. We investigated the influence of L-arginine (the precursor of NO
      synthesis), N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG)
      (inhibitors of NO synthase, with selectivity toward the constitutive and
      inducible isoforms, respectively) on the survival rate in a rat model of
      hemorrhagic shock. Anesthetized, male Sprague-Dawley rats (300-350 g) were
      subjected to hemorrhagic shock for 30 min followed by intravenous injection (1
      mL/kg) with normal saline, L-arginine (30 mg/kg), L-NAME (10 mg/kg), L-NAME+L
      arginine, AG (1, 10, 100 mg/kg) or AG (100 mg/kg)+L-arginine (n = 5 per group).
      Hemorrhagic shocked rats treated with saline died within 90 min. In contrast, L
      NAME increased the survival time to >72 h in shocked rats. AG (1, 10, and 100
      mg/kg) increased the survival time of shocked animals to 150 min, 230 min, and
      >72 h, respectively. Shocked rats treated with L-arginine died within 80 min, and
      those that received L-NAME+L-arginine and AG+L-arginine died within 120 min and
      110 min, respectively. L-NAME and AG (dose dependently) reduced macroscopic and
      microscopic injuries, nitrate/nitrite, PGE2 and creatinine production, and
      inhibited GOT activity in shocked animals. L-arginine reversed the beneficial
      effects of AG and L-NAME, suggesting the involvement of NO in the pathophysiology
      of hemorrhagic shock.

PMID- 9921718
TI  - In vitro macrophage endotoxin tolerance: defective in vitro macrophage map kinase
      signal transduction after LPS pretreatment is not present in macrophages from
      C3H/HeJ endotoxin resistant mice.
AB  - Altered endotoxin (LPS) signal transduction in macrophages (Mphi) may mediate
      development of organ dysfunction in sepsis. C3H/HeJ Mphi have a specific genetic
      defect that renders them "tolerant" to in vitro LPS activation. LPS tolerance can
      be induced in normal C3H/HeN Mphi following in vitro LPS pretreatment. In these
      experiments, in vitro LPS-stimulated activation of Mphi mitogen-activated protein
      (MAP) kinases were compared in C3H/HeJ and C3H/HeN mice. C3H/HeJ and C3H/HeN Mphi
      were cultured+/-10 ng/mL LPS pretreatment for 24 h, then stimulated with 0-1,000
      ng/mL LPS for 6 h. Western blots were performed on lysates with monoclonal
      antibody to active ERK1,2 (p42/44), stress-activated protein kinase (SAPK,
      p54/46), and p38 kinase. Supernatant TNF or IL-1 was determined by bioassay. High
      dose LPS stimulation activated ERK, SAPK, and p38 kinases in both C3H/HeN and
      C3H/HeJ Mphi. ERK activation, p46 SAPK, and p38 activation were inhibited in
      C3H/HeN Mphi after LPS pretreatment, whereas they were unchanged or increased in
      HeJ Mphi. TNF secretion was significantly decreased in C3H/HeN Mphi following LPS
      pretreatment, but absent in C3H/HeJ Mphi at all times. Mphi from normal C3H/HeN
      mice rendered endotoxin tolerant by in vitro, low dose LPS pretreatment have
      specific signal transduction defects that are not present in genetically LPS
      hyporesponsive C3H/HeJ mice.

PMID- 9921720
TI  - Cardiac contractility and structure are not significantly compromised even during
      the late, hypodynamic stage of sepsis. Mian Zhou, Ping Wang, and Irshad H.
      Chaudry. Shock 9(5):352-358, 1998.

PMID- 9921719
TI  - Contractile function and myoplasmic free Ca2+ (Cam) in coronary and mesenteric
      arteries of endotoxemic guinea pigs.
AB  - Endotoxin-induced vascular hyporesponsiveness could potentially involve
      alterations of vascular smooth muscle (VSM) myoplasmic free calcium (Ca(m))
      mobilization mechanisms. Contractile function and Ca(m)(fura-2 microfluorometry)
      regulation were evaluated in vitro using coronary (COR) and mesenteric (MES)
      artery preparations (100-250 microm inner diameter) isolated from guinea pigs 16
      h after intraperitoneal (i.p.) injection of either saline (control; CON) or
      Escherichia coli endotoxin lipopolysaccharide (LPS; 4 mg/kg). Concentration
      response relationships to K+ (5-100 mM) were significantly enhanced in both COR
      and MES arteries isolated from LPS-treated animals. In contrast, contractile
      responses to prostaglandin F2alpha (PGF2alpha; 1-100 microM) were markedly
      impaired in COR and MES arteries from LPS-treated animals, while endothelin-1
      (ET; 1-100 nM)-mediated contractile responses of these arteries were enhanced at
      the maximal dose (100 nM). In COR arteries, PGF2alpha (1-100 microM) and ET (1
      100 nM) produced biphasic increases in Ca(m) in both CON and LPS groups. No
      significant differences were observed in either the initial transient peak or
      secondary sustained Ca(m) responses between groups, suggesting a lack of effect
      of LPS upon intracellular Ca2+ release or Ca2+ influx mechanisms in COR arteries.
      Exposure of MES arteries to PGF2alpha and ET produced concentration-dependent
      increases in Ca(m) in both groups. However, Ca(m) responses of MES arteries
      lacked initial peak responses, suggesting potential differences in Ca(m)
      mobilization between COR and MES arteries. Ca(m) responses to K+ (80 mM) and
      PGF2alpha (1-100 microM) were similar in MES arteries from both groups; however,
      ET-mediated increases in Ca(m) were significantly blunted in LPS compared with
      CON MES arteries. Thus, endotoxemia produced differential effects upon
      depolarization (K4) and receptor (PGF2alpha, ET)-mediated contractile responses
      in both COR and MES arteries. Reductions in VSM Ca(m) mobilization appear
      unlikely as a mechanism for LPS-induced impairment of contractile function of COR
      and MES arteries; other mechanisms (i.e., decreased Ca2+ sensitivity of
      contractile proteins) may be involved in effects of LPS upon VSM function of COR
      and MES arteries.

PMID- 9921721
TI  - Personality and the subjective assessment of hearing aids.
AB  - Relatively little is known about the influence of patients' personality features
      on the responses they make to self-assessment items used to measure the outcome
      of a hearing aid fitting. If the personality of the hearing aid wearer has a
      significant influence on self-report outcome data, it would be important to
      explore the relevant personality variables and to be cognizant of their effects
      when using subjective outcome data to justify decisions about clinical services
      or other matters. This investigation explored the relationship between several
      personality attributes and responses to the Abbreviated Profile of Hearing Aid
      Benefit (APHAB). It found that more extroverted patients tend to report more
      hearing aid benefit in all speech communication situations. In addition, patients
      with a more external locus of control tend to have more negative reactions to
      loud environmental sounds, both with and without amplification. Anxiety also
      played a small additional role in determining APHAB responses. Although
      personality variables were found to explain a relatively small amount of the
      variance in APHAB responses (usually around 10%), these outcomes should alert
      practitioners and researchers to the potential effects of personality variables
      in all self-report data.

PMID- 9921722
TI  - Hearing aid outcome measures for children.
AB  - The provision of appropriate amplification for a young hearing-impaired child is
      critical as the aided speech signal will be used for the development of speech
      and language. The purpose of this paper is to provide an overview of the complex
      issues surrounding the documentation of hearing aid outcomes in the pediatric
      population. In the first two sections of the paper, the unique characteristics
      and needs of the pediatric population and factors complicating the measurement of
      outcome are described in detail. The third section provides a review of
      literature on existing outcome measures for children and the fourth section is
      devoted to a discussion of alternative approaches. The final section is an
      overview of clinical and research needs in the area of hearing aid outcome
      measures for children.

PMID- 9921723
TI  - Dimensions of hearing aid outcome.
AB  - Dimensions of hearing aid outcome are explored in this paper. First, a variety of
      hearing aid outcome measures is defined including objective and subjective
      performance, objective and subjective benefit, satisfaction, and use. Following
      the definition of these terms, factor analysis is described as a statistical tool
      that can be of assistance in establishing the number and nature of the relevant
      dimensions of hearing aid outcome. Next, the results from three recent studies
      that included a variety of measures of hearing aid outcome are examined and
      factor analysis is applied to the data from each study. This examination leads to
      the conclusion that hearing aid outcome is a multidimensional construct, rather
      than unidimensional. The most complete description of hearing aid outcome will be
      obtained when including at least one measure of aided speech recognition
      performance, one or more measures of objective benefit in speech recognition, one
      or two subjective measures of sound quality or listening effort, and one measure
      of either subjective benefit, satisfaction, or use.

PMID- 9921724
TI  - Perceived hearing aid benefit in relation to perceived needs.
AB  - A new scale, the Hearing Aid Needs Assessment (HANA), was developed in order to
      examine the relationship between perceived communication needs/expectations with
      the actual benefit eventually achieved with newly fitted hearing aids. A serial
      sample of 82 patients completed the HANA prior to hearing aid consultation. A
      subgroup of 42 patients eventually completed the Hearing Aid Performance
      Inventory after 2 to 3 months of new device use. The results indicated that
      candidates for amplification expect more benefit than they will typically
      achieve, especially when listening to speech in noise or without visual cues. For
      the most part, hearing aid benefit could not be reliably predicted based on
      perceived need or expectation.

PMID- 9921725
TI  - Some limitations of evaluative investigations based solely on normed outcome
      measures.
AB  - The present article argues that evaluative research in audiologic rehabilitation
      should be consistent with contemporary conceptual frameworks of rehabilitation.
      Moreover, comprehensive evaluative research investigations should include an
      evaluation of (1) the process of intervention and (2) the impacts and
      consequences of the intervention program. An approach to rehabilitation based on
      the principle that intervention should be viewed as a solution-centered problem
      solving process is outlined. Then, three illustrative cases are described and
      compared from the perspective of traditional evaluative research paradigms and
      from the perspective that audiologic rehabilitation is a solution-centered
      problem-solving process. Some shortcomings of traditional approaches to
      evaluative research are discussed. Finally, some guidelines that could lead to
      the development of comprehensive evaluative research in rehabilitation are
      outlined.

PMID- 9921726
TI  - Calculating hearing handicap.

PMID- 9921727
TI  - Transmission of measles among a highly vaccinated school population--Anchorage,
      Alaska, 1998.
AB  - During August 10-November 23, 1998, 33 confirmed measles cases were reported to
      the Anchorage Department of Health and Human Services and the Alaska Department
      of Health and Social Services (ADHSS). Of these, 26 cases were confirmed by
      positive rubeola IgM antibody test, and seven met the clinical case definition.
      This was the largest outbreak of measles in the United States since 1996. This
      report summarizes results of the epidemiologic investigation conducted by ADHSS
      and underscores the importance of second-dose requirements for measles vaccine.

PMID- 9921728
TI  - Preemptive state tobacco-control laws--United States, 1982-1998.
AB  - Cigarette smoking is the leading preventable cause of death in the United States.
      Environmental and policy interventions, particularly tobacco-control laws and
      regulations, are an important means to prevent and reduce tobacco use. For this
      study, preemptive legislation was defined as legislation that prevents any local
      jurisdiction from enacting restrictions that are more stringent than the state
      law or restrictions that may vary from the state law. One of the national health
      objectives for 2000 is to reduce to zero the number of states with preemptive
      smokefree indoor air laws (objective 3.25); a proposed objective for 2010 is to
      reduce the number of states with any preemptive tobacco-control laws to zero. To
      document trends in preemptive tobacco-control legislation at the state level, CDC
      identified state preemptive provisions and their effective dates from June 1982
      (the oldest provision currently in effect) to September 1998. This report
      summarizes the results of this analysis, which indicate an increase in the number
      of preemptive provisions from 1982 to 1996; no preemptive provisions in tobacco
      control laws have been enacted since 1996.

PMID- 9921729
TI  - Decrease in AIDS-related mortality in a state correctional system--New York, 1995
      1998.
AB  - The New York State Department of Correctional Services (NYSDOCS) administers one
      of the largest prison systems in the United States, with a population of
      approximately 70,000 inmates; in 1995, blinded seroprevalence studies indicated
      that an estimated 9500 inmates were infected with human immunodeficiency virus
      (HIV). This report summarizes an analysis of death records of inmates, which
      indicate a substantial reduction in the acquired immunodeficiency syndrome (AIDS)
      related deaths from 1995 through 1998 and describes the programs that may have
      contributed to this decline.

PMID- 9921730
TI  - Update: multistate outbreak of listeriosis--United States, 1998-1999.
AB  - From early August 1998 through January 6, 1999, at least 50 illnesses caused by a
      rare strain of the bacterium Listeria monocytogenes, serotype 4b, have been
      reported to CDC by 11 states. Six adults have died and two pregnant women have
      had spontaneous abortions. Reported illness onset dates were during August 2
      December 13, 1998. CDC and state and local health departments have identified the
      vehicle for transmission as hot dogs and possibly deli meats produced under many
      brand names by one manufacturer. This report updates the investigation of this
      outbreak.

PMID- 9921731
TI  - Paramedic use of a spinal injury clearance algorithm reduces spinal
      immobilization in the out-of-hospital setting.
AB  - OBJECTIVE: To determine whether paramedics can safely use a spinal clearance
      algorithm to reduce unnecessary spinal immobilization (SI) in the out-of-hospital
      setting. METHODS: Paramedics were instructed in the use of a spinal clearance
      algorithm that prompted assessment of the trauma patient's 1) level of
      consciousness, 2) drug and/or alcohol use, 3) loss of consciousness during the
      event, 4) presence of spinal pain/tenderness, 5) presence of neurologic deficit,
      6) concomitant serious injury, or 7) presence of pain with range of motion. The
      algorithm indicated that if any of the above were present, the patient should
      receive full SI, and if all of the above were negative, then SI could be
      withheld. Paramedics completed a tracking form that included the above and
      followed the patient to the emergency department (ED). Data were then gathered to
      determine the presence of spinal fracture, neurologic deficit, or a combination
      of the two. To compare the trends for SI, a retrospective medical incident report
      (MIR) review was conducted from the previous year. MIRs were selected based on
      the same criteria as those used for study inclusion. RESULTS: Two hundred eighty
      one patients were included in the study, with 65% (n = 183) of them receiving SI.
      Two hundred ninety-three MIRs were included in the retrospective sample, with SI
      being provided 95% (n = 288) of the time. Comparison of these samples shows a 33%
      reduction in utilization of SI (95% confidence interval: 27.2%- 38.8%).
      CONCLUSION: An out-of-hospital spinal clearance algorithm administered by
      paramedics can reduce SI by one-third. Any application of a spinal clearance
      algorithm should be accompanied by rigorous medical supervision.

PMID- 9921732
TI  - The choking child: what happens before the ambulance arrives?
AB  - OBJECTIVE: To compare pre-EMS intervention (bystander intervention) with EMS
      intervention (performed by fire department/EMS personnel) in the management of
      airway foreign bodies in children. METHODS: First-responding paramedic run
      reports for 1994 in the metropolitan area (city and county fire departments)
      pertaining to acute foreign body airway obstruction in children (aged 0-15 years)
      were reviewed. Data regarding age, gender, type of foreign body, method by which
      the airway was cleared, and mode of transportation were extracted. RESULTS: There
      were 103 runs with an age distribution as follows: 0-11 months 39.8%; 1-5 years
      50.5%; and >6 years 9.7%. Fifty-eight (56.3%) involved males and 45 (43.7%)
      involved females. Eighty-five percent of the airways were cleared before EMS
      arrival. Thirty-eight percent were self-cleared by the child. The chance of
      airway clearance before EMS arrival increased with increasing age: 78% of the
      children aged 0-11 months, 88.5% of the children 1-5 years of age, and 100% of
      the children aged 6 years or older had their airways cleared before EMS arrival.
      Forty-four percent of the children were not transported, and 27% were transported
      by private vehicle. Coins and food were the two most common foreign bodies.
      CONCLUSION: The majority of airway foreign bodies were cleared before EMS
      arrival, especially in older children. This supports CPR training of new parents
      and the general population and has training implications for the EMS provider in
      managing the pediatric airway.

PMID- 9921733
TI  - Actual vs perceived EMS response time.
AB  - OBJECTIVE: To compare patients' perceptions of ambulance response times with the
      actual ambulance response times to aid quality assurance efforts in EMS
      management. METHODS: A convenience sample of patients presenting to an urban ED
      via EMS were asked a series of four questions pertaining to response time, scene
      time, time to definitive care, and their expectations of response time. These
      times were then compared with actual times from the EMS dispatch center. Times
      were analyzed using multivariate analysis of variance (MANOVA) followed by
      discriminant analysis. RESULTS: There was a significant difference between the
      perceived and actual times for all three questions, by both multivariate analysis
      and univariate analysis (p < 0.0001). Patients tended to overestimate the actual
      response times (12.4 min vs 9.1 min) but underestimate the on-scene times (9.1
      min vs 12.4 min) and times to definitive care (29.4 min vs 35.0 min). CONCLUSION:
      Patients are inaccurate in their estimations of time. Response times are
      generally overestimated, while scene times and times to definitive care are
      underestimated. Actual response times often meet patients' expectations (mean
      10.8 min), although the patients may not perceive that they have.

PMID- 9921734
TI  - Response interval comparison between urban fire departments and ambulance
      services.
AB  - OBJECTIVE: To measure the response intervals of fire departments compared with
      ambulance services in three urban centers to determine whether defibrillators
      should be added to fire vehicles. METHODS: A prospective sample of 1,882 code 4
      (life-threatening) tiered calls were collected over a six-month period from March
      1, 1994, to August 31, 1994. A matched pairs experimental design compared the
      response interval of the fire department with that of the ambulance service for
      each call. This emergency medical services (EMS) system encompasses three urban
      centers with populations of 80,000, 95,000, and 170,000. RESULTS: In two of three
      of the urban centers, the fire department arrived on scene more than a minute
      sooner than the ambulance service: Cambridge (n = 571, mean = 2.22 min, p <
      0.0001); Kitchener (n = 1,011, mean = 1.24 min, p < 0.003); and Waterloo (n =
      300, mean = 0.69 min, p < 0.98). CONCLUSIONS: The shorter response interval of
      fire departments suggests placing defibrillators on fire response vehicles in an
      effort to decrease the time to defibrillation for cardiac arrest victims in this
      EMS system.

PMID- 9921735
TI  - State insurance commissioner actions against health maintenance organizations for
      denial of emergency care.
AB  - OBJECTIVE: Concerns have emerged from two west coast communities that health
      maintenance organizations (HMOs) may deter their members from calling 911. One
      means of influence is retrospective denial of emergency department (ED) or
      emergency medical services (EMS) claims. The study objective was to
      systematically assess legal action taken to contest HMO denial of claims.
      METHODS: Telephone survey of all state insurance commissioners (SICs). The
      specific question asked was: "What actions, if any, have been taken by the Office
      of Insurance Commissioner since 1990 against HMOs for denying claims for
      emergency department care or care provided by paramedics after a person has
      called 911?" Each office was contacted at least three times. RESULTS:
      Representatives from 49 states were interviewed. Three states (6%, Oregon, Texas,
      and Virginia) have taken formal action since 1990. Oregon fined two HMOs a total
      of $25,000 for inappropriate systematic claim denial of ED care. Texas fined one
      HMO $1,000,000 for similar practices. Virginia, with no authority to fine, has
      issued citations. No action had been taken for denying EMS claims. Thirty-eight
      states (78%) reported no formal actions. Eight (16%) state SICs could not easily
      retrieve these data and did not report. Fourteen (29%) representatives reported
      receiving these complaints. Most of these complaints were resolved without formal
      SIC action. CONCLUSIONS: Three health plans in two states received financial
      penalties for systematic denial of ED claims. A fourth was cited. This may
      underrepresent the true incidence of appealed ED and EMS claim denials. While
      complaints occurred in 29% of states, recent actions by SICs are relatively rare
      (6% of states). These results speak more to the extent systematic claim denials
      are discovered by SICs than to the true incidence of this practice.

PMID- 9921736
TI  - Initiation of capnography in a rural EMS system.
AB  - OBJECTIVE: Capnography is an effective means of monitoring cardiopulmonary
      resuscitation and managing endotracheal intubation. Numerous studies have
      validated its use in urban settings, but none have described its integration into
      a rural EMS system. The authors describe the process of integrating capnography
      training and use in Jackson County, West Virginia. METHODS: Two CO2SMOS
      capnography/ pulse oximeters were placed on the lead ambulances in Jackson
      County, West Virginia. Training in the operation and application of the equipment
      was provided, and providers used the monitors for a period of six months. A
      questionnaire was administered to assess their understanding of the equipment and
      its utility in prehospital care. Results were compiled and summarized. RESULTS:
      Ninety percent of the EMS providers subjectively felt that they understood
      capnography and its clinical application. They answered questions designed to
      test their understanding with 65% accuracy. CONCLUSION: In this model,
      capnography was successfully integrated into a rural EMS system. Reasonable
      proficiency in the use of the CO2SMOS monitor and an understanding of the
      information obtained were demonstrated, although the EMS providers tended to
      overestimate their actual understanding of the clinical application of
      capnography. This supports the need for ongoing, targeted education. The authors
      feel that capnography provides information that is uniquely relevant in rural EMS
      systems.

PMID- 9921737
TI  - The range of medication storage temperatures in aeromedical emergency medical
      services.
AB  - OBJECTIVES: The United States Pharmacopoeia (USP) recommends that medication
      storage temperatures should be maintained between 15 degrees C and 30 degrees C
      (59 degrees F to 86 degrees F). Concerns have been raised that storage
      temperatures in EMS may deviate from this optimal range, predisposing drugs to
      degradation. This study was conducted to determine whether temperatures inside
      the drug box carried by paramedics aboard a helicopter remained within the range.
      METHODS: The Aviation Section, with a paramedic on board, utilizes two
      helicopters and conducts approximately 80 patient care flights per month. A dual
      display indoor/outdoor thermometer with memory was used to measure the highest
      and lowest temperatures during each shift. The thermometer was kept with
      medications in a nylon drug bag, which remained on the helicopter except when
      needed for patient care. Ambient temperature measurements at the location of the
      helicopter base were obtained from the National Climatic Data Center. Temperature
      ranges were recorded during day shift (8 AM to 4 PM) and night shift (4 PM to 12
      AM) during the winter from December 1, 1995, to March 13, 1996, and summer from
      June 17, 1996, to September 14, 1996. Statistical analysis was performed using
      chi-square and the Bonferroni-adjusted t-test. RESULTS: Compared with the winter
      day period, the winter night period had lower minimum (13.2 degrees C vs 14.7
      degrees C, p = 0.003) and maximum (20.3 degrees C vs 21.2 degrees C, p = 0.02)
      temperatures. Both were below the USP minimum. The summer day period had higher
      maximum temperatures than the summer night period (31.2 degrees C vs 27.6 degrees
      C, p = 5 x 10(-9)). The mean daytime summer maximum exceeded the USP upper limit.
      Storage temperatures outside of the USP range were observed during 49% of winter
      days, 62% of winter nights, 56% of summer days, and 27% of summer nights. There
      was a significant tendency for summer days (p = 8 x 10(-8)) and winter nights (p
      = 0.009) to be outside of the acceptable range. There was moderate correlation
      between ambient and drug box temperatures (r2 = 0.49). CONCLUSIONS: Medications
      stored aboard an EMS helicopter are exposed to extremes of temperature, even
      inside a drug bag. Measures are needed to attenuate storage temperature
      fluctuations aboard aeromedical helicopters.

PMID- 9921738
TI  - An evidence-based evaluation of EMS protocols.
AB  - OBJECTIVE: To determine the extent to which prehospital patient care protocols
      incorporate the findings of the peer-reviewed scientific EMS literature. METHODS:
      Using a computerized literature search, articles published from eight
      institutions known to be active in prehospital care research were identified and
      obtained from the local health sciences library. Animal or bench research,
      analysis of administrative practices, evaluation of educational or quality
      assurance techniques, collective reviews, and air medical articles were excluded.
      We compared the findings of each article with the guidelines contained in 12 sets
      of prehospital care protocols, ranking them as: 1) consistent; 2) partially
      consistent; 3) not discussed; or 4) not consistent. The rankings for the article
      protocol comparisons for each EMS system were compared using the Kruskal-Wallis
      test. RESULTS: Forty-nine papers were compared with 12 sets of protocols,
      resulting in 588 comparisons. More than half (53.1%, n = 312) of the comparisons
      were ranked as "consistent." Only 28 (4.8%) of the comparisons were found to be
      "not consistent." There was no significant difference in the rankings assigned to
      the comparisons for protocols from each individual system, nor in the rankings
      for protocols from the EMS system associated with the source of the article, from
      other systems with academic affiliations, and from systems without academic
      affiliations. CONCLUSION: Most EMS protocols are consistent with the published
      peer-reviewed research. There is no difference in the level of consistency when
      comparing protocols from EMS systems associated with the source of the articles,
      those associated with other academic institutions, and those without strong
      academic affiliations.

PMID- 9921740
TI  - Current practice in clinical cervical spinal clearance: implication for EMS.
AB  - OBJECTIVES: To examine the practice of clinically "clearing" the cervical spine
      (c-spine) of trauma patients brought to the ED by EMS with cervical
      immobilization in place, and to examine developing trends in prehospital c-spine
      clearance. METHODS: A 12-question survey form was mailed to the physician medical
      directors of 300 randomly selected EDs. Questions examined ED clinical clearance
      practices, EMS clearance protocols and research, and attitudes toward prehospital
      clearance. Estimated clinical clearance rates were requested. RESULTS: A total of
      173 surveys were returned (58%). At 21 hospitals (12%), c-spine films are
      obtained for all immobilized trauma patients; clinical clearance is never
      attempted. Of the remaining 151 hospitals, on average, clinical clearance is
      attempted for 65.5% of these patients (range 3-100%, interquartile range 50-100%)
      and is successful (films are not obtained) for 53.7% of attempts (range 0-100%,
      interquartile range 35-75%). No differences exist in either attempt rate or
      success rate between trauma centers and non-trauma centers, or between
      academic/university hospitals, community teaching hospitals, and community non
      teaching hospitals (t-test or ANOVA, p > 0.05). Seventy-two respondents (42%)
      reported significant variation in clinical clearance practice patterns among
      their ED physicians. Seventy-three respondents (42%) feel that EMS providers
      should immobilize all trauma patients, while 99 (57%) feel it is reasonable for
      trained EMS providers to attempt clinical clearance on low-risk trauma patients.
      CONCLUSIONS: There is tremendous variation in the ED practice of clinically
      clearing cervical spines. This, and a lack of support from many ED directors, may
      hinder attempts at development of research and standardized protocols for pre
      hospital c-spine clearance.

PMID- 9921739
TI  - A death education curriculum for emergency physicians, paramedics, and other
      emergency personnel.
AB  - Although death education is a standard component in most medical schools and
      nursing programs, few include instruction on dealing with sudden death.
      Typically, death education courses overlook instruction in areas germane to
      emergency medicine, e.g., making death notifications, interacting with survivors
      during the immediate grief period, and reducing professional stress innate to
      working with newly bereaved persons. This curriculum was developed to address the
      paucity of existing death education materials for emergency professionals. Topics
      include death perspectives and awareness, death typology, cultural and religious
      considerations, communicating with bereaved persons, making death notifications,
      and dealing with initial grief reactions. Units of instruction are outlined,
      including educational goals, descriptions of units, teaching strategies, and
      supplemental readings.

PMID- 9921741
TI  - Tuberculosis screening: a review and a potential role for prehospital care
      providers.
AB  - Although tuberculosis has declined throughout this century, it has recently made
      a resurgence in our society. A major step in proper control measures is effective
      tuberculosis screening programs. Up to this point, prehospital care personnel
      have had a limited role in preventive medicine. In this article, it is proposed
      that prehospital care personnel can be a factor in the fight against tuberculosis
      through the conducting of tuberculin skin testing. The epidemiology of
      tuberculosis, tuberculosis control strategies, the current role of prehospital
      care in public health, the administration and interpretation of the tuberculin
      skin test, and tuberculosis high-risk groups are also reviewed.

PMID- 9921742
TI  - Development of an electronic emergency medical services patient care record.
AB  - OBJECTIVE: The need for valid and reliable emergency medical services (EMS) data
      has long been recognized. EMS data are useful for monitoring resources and
      operations, documenting patient care and outcome, and evaluating injury
      prevention strategies. The goal of this project was to develop a computerized
      data set with the capability to generate a patient care record (PCR) to overcome
      some of the current EMS data limitations. METHODS: The authors discuss developing
      an electronic PCR and analysis data set containing 233 variables. Data are
      collected for the following: incident, response, scene, patient, history, primary
      survey (including vital signs), physical examination, physiologic scores,
      diagnostics, plan (medications and procedures), assessment, and reevaluation.
      Software on a portable computer installed in an EMS response unit utilizes a
      graphical user interface for data collection by prehospital emergency care
      providers. A data set stores codes corresponding to user's selections. This data
      set supports data storage and analysis. The electronic PCR and data set can be
      useful to EMS agencies for collecting, storing, reporting, and analyzing
      information. RESULTS: Variables are categorized into 12 main categories to
      categorize the variables and to drive data collection. The system provides the
      user with the ability to print out a record (using a portable printer installed
      in an ambulance) and analyze data stored in the data set. CONCLUSION: This
      computerized approach overcomes many limitations inherent with using paper-based
      systems for research. Linked with emergency department, hospital discharge, and
      mortality data, EMS data can be used in systems analyses related to patient
      outcome.

PMID- 9921743
TI  - Institution of a police automated external defibrillation program: concepts and
      practice.
AB  - The authors have successfully implemented automated external defibrillation (AED)
      training in police departments that function as first responders. The initial
      elements are to think the project through, and to develop clear policies and
      procedures for the police as they relate to dispatching so there is timeliness of
      notification, because response time is such a critical element. Roles for all of
      the participants must be clearly defined and understood by all parties for such
      aspects as scene management, scene responsibility of care, and transfer of care
      to the receiving facilities. Communication to the entire health care community
      that the police have an expanded role in defibrillation is desirable. A system to
      evaluate training, compliance with protocol, and efficacy must be developed and
      closely monitored. While this is a tremendous amount of work and a large time
      investment, the result can be a dramatic increase in patient survival.

PMID- 9921744
TI  - The Kendrick extrication device used for pediatric spinal immobilization.
AB  - Immobilizing a child presents a unique challenge for emergency medical services
      (EMS) personnel in addition to those challenges faced when immobilizing an adult.
      Most equipment commonly carried by EMS personnel is sized for adult use and as a
      result does not routinely provide adequate static or dynamic immobilization of a
      child. In addition, children often resist immobilization and can free themselves
      from standard strapping techniques. These problems have led to the modification
      of existing equipment and the development of several pediatric-specific devices.
      An ideal pediatric immobilization device would be one that uses an existing piece
      of equipment, is of limited additional cost, is routinely used by EMS providers,
      could be easily modified to immobilize a child, could easily be taught to EMS
      providers, and provides excellent static and dynamic immobilization. The Kendrick
      extrication device (KED) used as the authors describe meets these goals of an
      ideal pediatric immobilization device.

PMID- 9921745
TI  - Is mechanism of injury dead?
AB  - Mechanism-of-injury data are frequently unavailable to the emergency physician.
      Furthermore, their value as a triage tool has recently been challenged. Motor
      vehicle crash patients have fewer external signs of injury, and commonly "look
      fine and feel fine" because of improvements in vehicle design, increased use of
      restraints, and airbag deployments. Yet forces involved in the crash may overcome
      all efforts at protecting the occupant, resulting in occult life-threatening
      injuries. Without data about the crash, physicians are blinded to violent crash
      forces that are ultimately transferred to the patient. Information technologies,
      such as on-scene photography by EMTs, automated collision notification systems,
      and telemedicine applications, may be used to deliver real-time crash information
      to aid the emergency physician in caring for these patients. Beyond improving
      patient care for any given encounter in emergency practice, collecting and
      evaluating these data will expand our knowledge about how to care for future
      motor vehicle crash patients.

PMID- 9921746
TI  - Inverse intubation: an important alternative for intubation in the streets.
AB  - One of the highest priorities for prehospital emergency personnel is airway
      management. Several rescuer positions for intubation on the ground have been
      published. Only recently, the inverse intubation method as an additional approach
      for intubation in the out-of-hospital setting has received further attention.
      Using four case reports, situations in which inverse intubation may be an
      important tool for successful airway management are discussed. Other uses of the
      method are listed.

PMID- 9921747
TI  - Field leg amputation by a paramedic.

PMID- 9921748
TI  - Initial survival from massive crush injury, leg avulsion, and hemicorpectomy.

PMID- 9921749
TI  - Arrest treatment without verification.

PMID- 9921750
TI  - An epizootic of lymphoplasmacytic gastritis attributed to Helicobacter pylori
      infection in cynomolgus monkeys (Macaca fascicularis).
AB  - An epizootic of subclinical lymphoplasmacytic gastritis occurred in cynomolgus
      monkeys maintained at our research facility. Gastric pathology data and
      histologic sections of 63 adolescent monkeys (2.5-3.5 years old) sacrificed
      during the epizootic were reviewed. Localized to multifocal reddening of the
      gastric mucosa was noted grossly in 7 of 44 (16%) monkeys harboring Helicobacter
      pylori, but not in any of 19 monkeys in which these bacteria were not seen.
      Gastritis, characterized by accentuation of lymphoplasmacytic infiltrates in
      antral and to a lesser degree cardiac mucosa, occurred in 42 of 63 (67%) monkeys
      evaluated and in 42 of 44 (93%) monkeys in which H. pylori was observed
      microscopically. Two monkeys with H. pylori infection had infiltrate scores that
      overlapped with the upper limit of scores of H. pylori-negative animals.
      Coincident with accentuated infiltrates were gastric gland epithelial
      hyperplasia, reduction in mucin content of surface and gland epithelia, and
      comparatively minor infiltrates of neutrophils in superficial lamina propria and
      gastric glands. Antral mucosa thickness often exceeded 1.5 to 2 times normal.
      Antral mucosal erosions occurred in 7 of 44 (16%) monkeys with H. pylori.
      Argyrophilic bacteria morphologically consistent with H. pylori were present in
      antral and less commonly cardiac mucosal glands. Intensity of bacterial
      colonization correlated with lymphoplasmacytic infiltrates (r = 0.754) and
      hyperplasia (r = 0.700), although responses were quite variable. These bacteria
      were not detected in fundic mucosa except in instances where parietal cells were
      substantially depleted in glands coincident with localized increases in lamina
      propria inflammatory cell infiltrates. Helicobacter heilmannii-like organisms
      (HHLOs) were present in fundic glands of all 63 monkeys; colonization was often
      pronounced. Scores for fundic mucosal inflammation did not correlate with
      presence or intensity of colonization with HHLOs (r = 0.005). Rather, fundic
      inflammation scores positively correlated with the antral inflammation scores (r
      = 0.548). Bacteria morphologically, biochemically, and genetically consistent
      with H. pylori were cultured from gastric mucosal specimens confirming bacterial
      identification. These findings demonstrate that adolescent cynomolgus monkeys are
      susceptible to natural infection with H. pylori and develop many morphologic
      hallmarks of H. pylori-related gastritis in humans.

PMID- 9921751
TI  - Glomerulosclerosis in captive cheetahs (Acinonyx jubatus).
AB  - The cheetah (Acinonyx jubatus) is an endangered species with low fecundity and
      premature death in captivity. A previous survey determined that renal failure as
      a result of glomerulosclerosis was a major cause of death in captive populations.
      This study characterizes the morphologic, histochemical, and epidemiologic
      properties of glomerulosclerosis in this population. Kidneys from 87 cheetahs
      were examined by light microscopy; kidneys from six of those cheetahs were
      examined by electron and fluorescent microscopy using special stains specific for
      collagen, glycoproteins, reticulin, and fibrin. Immunohistochemistry for the
      advanced glycosylation end products (AGEs), pyrraline and pentosidine, also was
      performed on these cases. Glomerulosclerosis was present to some degree in 82% of
      the population, and in 30% of cheetahs the sclerosis was moderate to severe.
      Affected cheetah kidneys had thickened glomerular and tubular basement membranes,
      culminating in glomerulosclerosis. Thickened basement membranes were positive for
      collagen, glycoproteins, reticulin, and AGEs. Ultrastructurally, membrane
      material was homogeneous and fibrillar without electron-dense deposits. This
      glomerular lesion in cheetahs resembles diabetic glomerulopathy in humans and
      chronic progressive nephropathy in rats. No cheetahs had lesions of diabetes.
      However, adrenal cortical hyperplasia was prevalent and highly correlated with
      glomerulosclerosis in this population. If cheetahs with glomerulosclerosis had
      hypercorticoidism, then hyperglycemia and glomerular hypertension could lead to
      progressive AGE and plasma protein accumulations in membrane lesions. As in rats,
      daily feeding of high-protein diets and lack of genetic variation in the
      population may further contribute to the high prevalence of glomerulosclerosis in
      captive cheetahs.

PMID- 9921752
TI  - Prognostic value of histopathological grading in canine extramedullary
      plasmacytomas.
AB  - The canine extramedullary plasmacytoma (cEMP) has recently been the subject of
      numerous investigations, indicating that the histomorphologic diagnosis is often
      difficult because of the variety of morphologic features. Therefore, the
      objective of this study was to establish a subclassification scheme for cEMPs and
      to evaluate correlations between the types and malignancy. Retrospectively, 117
      cEMPs, all immunohistochemically characterized by a monoclonal immunoglobulin
      light-chain expression, were collected and assigned to morphologic types. These
      types were compared using data from a follow-up study on metastasis and tumor
      recurrence, then compared by proliferation rate, determined by
      immunohistochemical detection of the antigen Ki-67. Histopathologic typing
      revealed five different types of cEMPs, ranging from the mature type with typical
      plasma cells to the polymorphous-blastic type. Between these two forms, three
      additional types were established: hyaline, cleaved, and asynchronous. Most of
      the cEMPs were of the cleaved and asynchronous types. In all cEMPs, mononuclear
      and multinuclear giant cells were present to varying degrees. Although the
      results of cell proliferation and the follow-up study indicated less benign
      behavior by the polymorphous-blastic type, the proliferation rate revealed no
      statistically significant differences among the cEMP types. The clinical data
      therefore confirmed previous findings that the risk of tumor recurrence and
      metastasis in general can be classed as low. The established cEMP typing system
      is probably a very helpful diagnostic tool, although the types cannot be used for
      a tumor grading system.

PMID- 9921753
TI  - Angiomatosis, a newly recognized disease in Atlantic bottlenose dolphins
      (Tursiops truncatus) from the Gulf of Mexico.
AB  - A new disease, angiomatosis, was recognized in 25 of 54 (46.3%) Atlantic
      bottlenose dolphins (Tursiops truncatus) necropsied after being stranded along
      the Texas Gulf coast during 1991-1996. Angiomatosis was first recognized by the
      authors in 1992 and has increased in incidence and severity, affecting 100% of
      juveniles and adults. This disease is characterized by proliferation of small,
      thick-walled blood vessels diffusely throughout the lungs, without inflammation,
      exudation, or alveolar hemorrhage. The vascular proliferation also occurs in lung
      associated and other visceral lymph nodes. Hemangiomas frequently occur in
      affected lymph nodes and occasionally in the lungs. The vascular proliferation
      reduces airspace and may occlude small airways. Angiomatosis appears to be a
      broad-field defect of vascular endothelium. Although this process appears to be
      an increasingly important factor in the morbidity of T. truncatus, its etiology
      has not been determined.

PMID- 9921754
TI  - Proliferative potential of canine oral epulides and malignant neoplasms assessed
      by bromodeoxyuridine labeling.
AB  - The proliferative potential of canine oral lesions, including epulides, squamous
      cell carcinomas, a malignant melanoma, and a fibrosarcoma, was examined using a
      monoclonal antibody to bromodeoxyuridine (BrdU). Twenty-three dogs with oral
      masses were administered BrdU intravenously at a dose of 8 mg/kg 1 hour before
      surgery, and the BrdU labeling index (LI) of each lesion was determined
      immunohistochemically. The average BrdU LIs for the main proliferating elements
      in the fibromatous epulis (4 cases), ossifying epulis (2 cases), and
      acanthomatous epulis (10 cases) were 4.9, 3.0, and 8.8%, respectively. The
      squamous cell carcinomas (5 cases) had an average LI of 15.9%, and the LIs of the
      malignant melanoma and fibrosarcoma were 7.5 and 10.3%, respectively. All cases
      of acanthomatous epulides and squamous cell carcinoma treated with simple
      marginal surgical resection recurred within a short time. The higher LIs in the
      acanthomatous epulides, squamous cell carcinomas, and fibrosarcoma correlate well
      with their poor prognoses, reflected by rapid growth and frequent recurrence.
      Acanthomatous epulis is clearly distinguished from other epulides by its
      aggressive clinical behavior and high proliferative potential, which is
      equivalent to that of malignant tumors, despite a lack of cell atypia. The BrdU
      LI is a useful marker for evaluating the proliferative potential and prognosis of
      canine oral tumors.

PMID- 9921755
TI  - Prominence of gammadelta T cells in the elicitation phase of dinitrochlorobenzene
      induced contact hypersensitivity in lambs.
AB  - Immunohistochemical techniques were used to identify T-cell subpopulations in the
      ear skin of lambs during the elicitation phase of dinitrochlorobenzene (DCNB)
      induced contact hypersensitivity. Thirty lambs (21-26 weeks of age) were divided
      into groups of 10. The shaved right ear of one group was treated with DNCB. Two
      weeks later, this group was challenged with DNCB. One group was treated with the
      vehicle alone, and the remaining group was left untreated. The lambs were killed
      48 hours after challenge, and tissue specimens were collected from the ears of
      the three groups. There was an increase in T-cell populations in the skin of the
      DNCB-treated lambs 48 hours after challenge. The majority of the T cells were
      CD8+ and associated predominantly with the blood vessels and adnexa of the
      superficial dermis. There was also an increased presence of CD4+ cells and
      gammadelta T cells in the superficial dermis. In the epidermis, clusters of
      gammadelta T cells and CD4+ cells were associated with microlesions. Computer
      assisted morphometric analysis was used to estimate the relative presence of the
      T-cell subpopulations in the superficial and deep dermis and the entire dermis.
      Statistical analysis of the relative area of immunostaining showed that the
      significant increases in all T-cell subpopulations (CD4+, CD8+, and gammadelta T
      cells) in the entire dermis were accounted for by changes in the superficial
      dermis. The prominence of gammadelta T cells in delayed-type hypersensitivity in
      the skin of domestic ruminants has been the subject of conflicting reports. In
      the present study, CD4+ cell and gammadelta T-cell populations were of similar
      size in the normal and DNCB-treated lambs, suggesting an equal participation in
      the elicitation phase of contact hypersensitivity.

PMID- 9921756
TI  - Immunohistochemical studies of productive rhesus cytomegalovirus infection in
      rhesus monkeys (Macaca mulatta) infected with simian immunodeficiency virus.
AB  - In humans infected with the human immunodeficiency virus (HIV), clinical disease
      due to human cytomegalovirus (HCMV) infection is one of the AIDS-defining
      diseases; HCMV is the most common opportunistic infection found postmortem.
      Histologically, the typical lesions are characterized by "owl's eye cells." In
      rhesus monkeys infected with simian immunodeficiency virus (SIV), comparable
      lesions are caused by an infection with the rhesus CMV (RhCMV). The aim of this
      study was to investigate the incidence of productive and latent RhCMV infection
      in monkeys infected with SIV macaques (SIVmac). Eleven SIVmac-infected rhesus
      monkeys, which were euthanatized after developing AIDS-like disease, and 11
      clinically healthy and uninfected animals comprised the study. The monkeys were
      screened serologically for RhCMV by western-blot analysis. Immunohistochemistry
      was performed by an indirect immunoperoxidase technique with a polyclonal rabbit
      RhCMV-antiserum. Lesions characteristic of RhCMV-associated diseases were
      detected histologically. All animals were latently RhCMV-infected. Seven of
      eleven (63.6%) SIV-infected macaques were productively RhCMV infected according
      to immunohistochemistry. RhCMV antigen was identified in the gastrointestinal
      tract, the hepatobiliary system, the lungs, and the testicles. Two of these seven
      animals showed characteristic inflammatory lesions associated with productive
      infection. Consequently, the CMV prevalence in SIVmac-infected rhesus monkeys and
      human AIDS patients is comparable.

PMID- 9921758
TI  - Perosomus elumbis (vertebral agenesis and arthrogryposis) in a stillborn Holstein
      calf.
AB  - Perosomus elumbis, an infrequently encountered congenital anomaly of unknown
      etiology, was studied in a female Holstein calf. This error of morphogenesis
      represents a set of multiorgan malformations that produce a deformity of the
      caudal one third of the fetus. In this case, the spinal and pelvic malformations
      were radiographed and then dissected. Intra-abdominal abnormalities of the soft
      tissues are also described. The normal sequential embryologic development of the
      vertebrate skeleton, anterior-posterior fetal positioning, and neural tube
      migration are discussed. An extensive literature of this birth defect in cattle
      (and sheep) is reveiwed. The reports from a period covering 165 years are
      compared with the pathologic features in this case. Chromosomal aberrations
      within the homeobox gene family are postulated to be contributory factors in the
      development of this type of dysorganogenesis.

PMID- 9921757
TI  - Expression of surfactant protein mRNA in normal and neoplastic lung of B6C3F1
      mice as demonstrated by in situ hybridization.
AB  - The localization of surfactant protein (SP), A, B, C, and D mRNAs was examined in
      B6C3F1 mice in the normal lung, and in a range of spontaneous proliferative lung
      lesions using nonisotopic in situ hybridization (ISH). The aim was to develop
      diagnostic markers, and if possible, throw further light on the histogenesis of
      these lesions. Tissues from 21 animals were examined, the lesions studied were: 4
      alveolar epithelial hyperplasias, 12 alveolar/bronchiolar (A/B) adenomas, and 5
      A/B carcinomas. Lung metastases of hepatocellular carcinoma (HCC) were used as
      controls. In the nonneoplastic lung, staining for SP A, B, and C mRNA was
      observed in normal and hyperplastic type II cells but not in the bronchiolar
      epithelium. SP mRNAs were present in all lung tumors, with SPs A, B, and C being
      coexpressed in 10/12 (83%) of adenomas and 4/ 5 (80%) of carcinomas in both solid
      and tubulopapillary areas. No signals for SP D mRNA were noted in normal or
      neoplastic lung. Additionally, no staining for any SP transcript was observed in
      the HCC metastases examined. In summary, ISH for SP A, B, or C mRNA was a helpful
      aid in the diagnosis of proliferative lesions of the murine lung, enabling
      differentiation from hepatocellular metastases. Furthermore, this work provides
      strong support for the proposal that spontaneous lung tumors in B6C3F1 mice are
      of alveolar, not bronchiolar origin, and consistently show type II cell
      differentiation. We suggest that such tumors should be referred to as alveolar
      adenomas and carcinomas.

PMID- 9921759
TI  - Extraskeletal osteosarcoma of the mandibular salivary gland in a dog.
AB  - A 14-year-old spayed female shepherd/collie crossbred dog had a 6 x 4-cm mass
      excised from below the right ear. The partially encapsulated, neoplastic mass had
      a necrotic core and was embedded in the mandibular salivary gland.
      Histologically, the mass was composed of numerous multinucleate giant cells and
      large, oval, pleomorphic cells that produced osteoid. Neoplastic cells were
      immunoreactive for vimentin and actin but not for keratin, desmin, or S-100
      protein. At postmortem examination 1 month later, an 11-cm spherical mass had
      recurred at the surgical site, and there were metastatic nodules in the lungs,
      ipsilateral mandibular lymph nodes, and kidney. The tumor was diagnosed as an
      osteosarcoma of the mandibular salivary gland with pulmonary, lymphatic, and
      renal metastasis. In addition, a 17-year survey of canine salivary-gland
      neoplasms revealed that most were adenocarcinomas or carcinomas.

PMID- 9921760
TI  - Oral malignant melanoma with osteoid formation in a dog.
AB  - Melanomas are the most frequent malignant neoplasms of the oral cavity of dogs.
      Osteogenic melanoma is a rare variant of melanoma that has been described in
      humans but not in animals. We describe a case of malignant melanoma with bone
      production affecting the gingiva of a 12-year-old Miniature Dachshund dog. The
      tumor was a round, lightly pigmented mass that measured 1 cm in diameter and was
      hard to cut. Histologically, the tumor was composed of nests and lobules of
      anaplastic, round, melanin-containing cells supported by a stroma displaying
      abundant osteoid matrix. Many of the neoplastic melanocytic cells were in close
      contact with the osteoid trabeculae. Immunohistochemical tests revealed that the
      neoplastic cells were immunoreactive for S-100 and vimentin and showed no
      staining with cytokeratin. The animal had a local recurrence of the tumor 3
      months after the initial excision. This is the first case of malignant melanoma
      with osteoid formation reported in animals.

PMID- 9921761
TI  - Subacute massive necrotizing myocarditis by canine parvovirus type 2 infection
      with diffuse leukoencephalomalacia in a puppy.
AB  - Severe necrotizing myocarditis associated with canine parvovirus type 2 (CPV-2)
      infection and diffuse leukoencephalomalacia was recognized in a 4-week-old
      mongrel puppy. The cardiac lesions were characterized by severe diffuse
      myocardial degeneration and necrosis with occasional massive mineralization and
      distinct intranuclear inclusion bodies. Immunohistochemical examination revealed
      the presence of CPV-2 antigens in both the cytoplasm and nuclei of the myocytes.
      In the white matter of the cerebrum, moderate to severe diffuse necrosis with
      diffuse infiltration of gitter cells and occasional diffuse mineral deposits were
      recognized symmetrically and bilaterally. In the meningocortical area of the
      cerebellum, there was mild focal hemorrhage and accumulation of hemosiderin-laden
      histiocytes. In addition to the absence of viral antigen (as judged by
      immunohistochemistry), neither viral inclusions nor other vascular lesions were
      identified in examined sections of brain. These findings suggest that the brain
      lesions were not induced by direct CPV-2 infection but were related to severe
      myocardial lesions producing prolonged hypoxia and/or ischemia.

PMID- 9921762
TI  - Generalized dermal dysplasia and perifollicular mucinosis in a dog.
AB  - Multiple nodules 0.5-2 cm in diameter were observed in the dorsal skin of a 1.5
      year-old male castrated mongrel dog. Histopathologically, perifollicular
      mucinosis and clusters of small cells with a dense, round nucleus and scant
      cytoplasm were seen. The small cell clusters were present in the dermis near the
      epidermal basal layer or surrounding hair follicles. These cells demonstrated
      different staining patterns for vimentin and keratin depending on their location;
      ultrastructurally, they were poor in organelles and connected to each other with
      cytoplasmic projections. These findings suggested that they were immature
      epithelial cells. The case was diagnosed as generalized dermal dysplasia and
      perifollicular mucinosis.

PMID- 9921763
TI  - Congenital fibropapillomatosis in a piglet.
AB  - We report a case of congenital fibropapillomatosis in the head and neck of a
      piglet from a swine breeding farm where sporadic cutaneous papillomas of the
      prepuce and scrotum had previously occurred in several boars. Histologically, the
      tumor consisted of multiple exophytic, papillary projections composed of
      branching, densely cellular, fibrovascular stalks covered by hyperplastic
      keratizing squamous epithelium. Ultrastructural examination failed to reveal
      viral particles. Cutaneous papillomatosis is rare in swine. To the best of our
      knowledge, this is the second report of congenital fibropapillomatosis in pigs.

PMID- 9921764
TI  - Stress reduction for fun and profit.

PMID- 9921766
TI  - Fibromatosis of the plantar fascia: diagnosis and indications for surgical
      treatment.
AB  - Plantar fibromatosis is a rare, benign lesion involving the plantar aponeurosis.
      Eleven patients (13 feet) underwent 24 operations, including local excision, wide
      excision, or complete plantar fasciectomy. Clinical results were evaluated
      retrospectively. There were no differences among the subgroups in postoperative
      complications. Two primary fasciectomies did not recur. Three of six revised
      fasciectomies, seven of nine wide excisions, and six of seven local excisions
      recurred. Our results indicate that recurrence of plantar fibromatosis after
      surgical resection can be reduced by aggressive initial surgical resection.

PMID- 9921765
TI  - Proximal phalanx osteotomy for the surgical treatment of hallux rigidus.
AB  - This study reviewed 17 patients (24 great toes) treated by a single surgeon for
      hallux rigidus with a dorsal-closing wedge osteotomy of the proximal phalanx in
      conjunction with a moderate cheilectomy. The average age of patients was 47 years
      (range, 20-69 years). The minimum follow-up was 1 year (range, 1-16 years; median
      follow-up, 30 months), and all but five patients were studied for 2 years or
      more. Ninety-six percent of patients affirmed their decision to have surgery if
      they had to make the choice again. Subjectively, all patients improved.
      Preoperatively, 67% of the cases had severe pain by American Orthopaedic Foot and
      Ankle Society criteria. Postoperatively, 58% had no pain and 42% had mild pain.
      There was 100% union rate of the osteotomy. Seven of 10 women and 1 of 7 men
      still had some restrictions on footwear options postoperatively. Recovery time
      from the patients' perspective was 2 to 12 months (average, 5.6 months). Based on
      the results of this study, the authors suggest that the addition of a dorsal
      closing wedge osteotomy of the proximal phalanx increases patient satisfaction,
      compared with their review of patients treated by cheilectomy alone. The
      procedure provides good pain relief and has few complications.

PMID- 9921767
TI  - Results of in situ subtalar arthrodesis for late sequelae of calcaneus fractures.
AB  - A retrospective review was performed on all patients who had an in situ subtalar
      arthrodesis for painful sequelae of calcaneus fractures between 1989 and 1994.
      Nineteen feet were available for evaluation, with a mean follow-up of 27 months
      (range, 12-62 months). Lateral calcaneal wall decompression was performed in
      seven feet. Although loss of ankle dorsiflexion was associated with anterior
      ankle tenderness, loss of ankle dorsiflexion was not correlated with either talar
      declination angles or talar height differences. There was no correlation between
      American Orthopaedic Foot and Ankle Society hindfoot score and talar declination,
      talar height, or calcaneal width. Peroneal tendon/subfibular impingement, ankle
      tenderness, sural nerve injury, and patient smoking were all statistically
      associated with lower scores. The calcaneocuboid joint was frequently involved in
      the fracture but was not painful at follow-up. Late pain after a calcaneal
      fracture is not caused by only subtalar arthrosis. Radiographic criteria alone
      cannot be relied upon for surgical decision making. Careful physical evaluation
      should be used to determine sources of pain. Distraction arthrodesis should be
      considered only if findings of anterior ankle impingement are present. If sural
      nerve symptoms are present, a sural neurectomy may be added to the procedure.
      Pain localized to the plantar fat pad should be managed nonoperatively.
      Radiographic changes in the calcaneocuboid joint rarely require surgical
      intervention. Based on these results, in situ subtalar arthrodesis with lateral
      wall decompression is the procedure of choice in most cases of subtalar traumatic
      arthritis with lateral wall impingement.

PMID- 9921768
TI  - Radiographic evaluation of talonavicular joint after talar screw placement: a
      cadaver study.
AB  - Twelve cadaver feet were used for a radiographic assessment of the talonavicular
      joint. A 4.0- or a 6.5-mm screw was inserted through the posterior tubercle of
      the talus, directed anteriorly into four quadrants of the talar head. Lateral,
      dorsoplantar, lateral oblique, and medial oblique radiographic views were
      obtained for each specimen, to assess the position of the screw tip in relation
      to the talonavicular joint. The lateral view consistently demonstrated the screw
      tip violation when the screw was directed through the center of the talar head,
      but it failed when screws were passed into the medial or lateral quadrants of the
      talar head. The dorsoplantar view consistently demonstrated a screw tip violation
      of the superior two quadrants of the talar head when other views failed. Each
      screw tip violation of the inferior quadrants (medial and lateral) required a
      different view. A screw tip violation of the inferior medial quadrant required
      the lateral oblique view, whereas the inferior lateral quadrant required the
      medial oblique view for full appreciation. Here again, other views failed to
      demonstrate minor screw tip violations consistently. Using these views to assess
      screw placement could decrease the risk of developing posttraumatic arthritis
      caused by screw tip violation of the talonavicular joint.

PMID- 9921769
TI  - Clinical significance of increased mobility in the sagittal plane in patients
      with hallux valgus.
AB  - Hallux valgus (HV) deformity is not always accompanied by pain. We compared
      roentgenograms of 32 feet of people with HV deformity and pain to roentgenograms
      of 22 feet of people with painless HV deformity. Twenty-three feet without HV
      deformity or pain were used as controls. Weightbearing and nonweightbearing
      roentgenograms of the lateral talar-first metatarsal angle showed a statistically
      significant difference between feet with deformity and pain compared with feet
      with painless HV, or compared with normal feet. Changes in the angles of HV
      between weightbearing and nonweight-bearing situations showed significant
      differences between HV feet and normal feet, whether or not they had pain. In HV
      patients, increased mobility in the sagittal plane may play a considerable role
      in the development of pain.

PMID- 9921770
TI  - Biomechanical evaluation of two different screw positions for fusion of the
      calcaneocuboid joint.
AB  - In triple arthrodesis performed for severe deformity and neuroarthropathy in
      poorly compliant patients with osteoporotic bone, fixation of the arthrodesis is
      critical. We biomechanically tested an alternative means of stabilization for
      calcaneocuboid fusions. In seven matched pairs of fresh-frozen cadaver feet, we
      removed the soft tissue from around the calcaneocuboid joint, except for the
      capsule, and we did not resect the articular cartilage. One joint of each pair
      was fixed with an oblique standard screw, and the contralateral joint was
      stabilized with an axial screw placed perpendicularly to the joint surface.
      Testing on an MTS Mini Bionix Test Frame (MTS Systems Corp., Eden Prairie, MN)
      demonstrated that the axial screw provided significantly higher initial stiffness
      and maximum load to failure. We concluded that an axial screw provided better
      fixation of the calcaneocuboid joint.

PMID- 9921771
TI  - Treatment of complex calcaneal fractures with bony defects from land mine blast
      injuries with a circular external fixator.
AB  - Four calcanei, which were massively destroyed as a result of blasting injuries
      from land mines, and 18 severely comminuted calcaneal fractures with bony defects
      (in one patient, both feet), also from land mines, were treated using a circular
      external fixator for reconstruction by osteogenic distraction. Because of the
      severe destruction of tissue to be treated, definitive orthopaedic treatment was
      delayed for 3 to 28 months (average, 10.1 months) after injury. Time from first
      use of the circular external fixator to removal of the apparatus ranged from 110
      to 175 days (average, 143.7 days). Mean follow-up was 18 months. Of the 22
      calcaneal injuries, 4 had excellent results, 11 good, 5 fair, and 2 had poor
      results. Better results were achieved in cases with lesser defects in bone and
      where definitive orthopaedic treatment was delayed until problems in soft tissue
      could be treated.

PMID- 9921772
TI  - Idiopathic pseudoaneurysm of the dorsalis pedis artery mimicking pigmented
      villonodular synovitis.
AB  - Pseudoaneurysm of the dorsalis pedis artery is uncommon and is usually associated
      with a history of trauma to the vessel. Without such a history, the diagnosis may
      be challenging, because the mass may be confused with other common soft tissue
      masses in the foot. This case report describes a 67-year-old man with an
      idiopathic pseudoaneurysm of the dorsalis pedis artery that mimicked pigmented
      villonodular synovitis.

PMID- 9921773
TI  - Rank order analysis of tibial plafond fractures: does injury or reduction predict
      outcome?
AB  - We investigated the effects of severity of initial injury pattern and the quality
      of the articular reduction on outcome of displaced intra-articular distal tibial
      fractures, using a series of 25 patients who were treated with articulated
      external fixation and limited internal fixation, which provided a spectrum of
      reduction quality. Outcome was assessed by clinical ankle scores and radiographic
      arthrosis. The results demonstrate the rank order method to be a reliable means
      of stratifying severity of injury and quality of reduction. Neither injury nor
      reduction correlated with clinical ankle score. Reduction had a significant
      correlation with radiographic arthrosis. We conclude that the rank order method
      is useful in stratification of fracture patients, and that factors other than
      injury pattern and quality of articular reduction are important in determining
      outcome of patients with this severe articular injury.

PMID- 9921774
TI  - Open reduction and internal fixation of fracture of the posterior process of the
      talus: a case report and review of the literature.
AB  - A fracture of the posterior process of the talus is rare. In this report, we
      present a case of isolated displaced fracture of the posterior process of the
      talus, which was treated by early open reduction and internal fixation through a
      posteromedial approach. The fracture healed without evidence of avascular
      necrosis of either the posterior fragment or the talar body. The purpose of this
      article is to highlight the importance of early postoperative management of this
      uncommon type of fracture.

PMID- 9921775
TI  - Modification of the Kidner procedure with fusion of the primary and accessory
      navicular bones.

PMID- 9921776
TI  - Natural selection and high heels.

PMID- 9921777
TI  - Highlights of the Fourteenth Annual Summer Meeting of the American Orthopaedic
      Foot and Ankle Society, Boston, Massachusetts, July 24-26, 1998.

PMID- 9921778
TI  - A new modified technique for harvest of calcaneal bone graft in surgery on the
      foot and ankle.

PMID- 9921779
TI  - Emotional intelligence: a missing ingredient?

PMID- 9921780
TI  - Rhetoric to practice: the challenge of collaboration of academe and industry.
AB  - Community health nursing is a complex practice that encompasses nurses working in
      many diverse settings. This article discusses the development of a project which
      focused on better preparation of students for potential employment in community
      settings. The formation of the working team and the development of the curriculum
      is outlined. A focus is given to the linking of primary health care principles in
      the teaching and facilitation of students within hospital and community settings.
      Comprehensive conclusions cannot be made yet from the project's preliminary
      findings. However, the process of collaboration has demonstrated several issues.
      These will have an impact on everyone who has been part of this project, and the
      issues are discussed in this article. The article provides an overview of the
      first year of collaboration of a 4-year project.

PMID- 9921781
TI  - Self-health appraisal: learning the difficulties of lifestyle change.

PMID- 9921782
TI  - A model for collaborative nursing and medical education within the context of
      family violence.

PMID- 9921783
TI  - Transcending behaviorism in communication education.
AB  - During the past decade, nursing education has been engaged in a curriculum
      revolution. Although this ongoing revolution has led to profound changes in
      nursing curricula, one area that requires further scrutiny is communication
      education. This article addresses the limitations of behavioral communication
      curricula and suggests a pedagogical process responsive to the complexity of
      human caring relationships and the intricacies of relational practice. The
      discussion includes a description of a nursing communication course developed
      according to the principles of transformational learning theory.

PMID- 9921784
TI  - History of higher education: educational reform and the emergence of the nursing
      professorate.
AB  - At the end of the 19th century and prior to any published nursing theories, a
      number of visionaries in the field of nursing were engaged in the pursuit of a
      liberal education for nurses. These special people, rarely considered in
      contemporary nursing curricula, were responsible for moving nursing education out
      of hospitals and into universities. This shift was primarily responsible for the
      development of nursing professors, which never may have developed had nursing
      education remained under the auspices of hospitals.

PMID- 9921785
TI  - Breaking through the hegemony of homogeneity: revitalizing curriculum and
      students.
AB  - Undergraduate programs provide fertile ground from which future practitioners,
      researchers, and teachers of psychiatric mental health nursing will emerge.
      Health care has changed dramatically, offering opportunities for new and
      innovative roles and prompting faculty to develop novel ways of thinking about
      the future role of psychiatric nurses. Nursing faculty are challenged to devise
      new and creative approaches to teaching psychiatric nursing at the undergraduate
      level in ways that will instill enthusiasm for the field. In this article, the
      efforts of the University of Pennsylvania to approach psychiatric mental health
      courses in new ways will be described. These innovations are designed to
      stimulate passion for what the authors see as a complex and exciting field that
      requires revitalization.

PMID- 9921786
TI  - From vocational training to academic education: the situation of the schools of
      nursing in Sweden.
AB  - As a consequence of a college reform in 1993, nursing education in Sweden is
      changing from vocational training to academic education. Teacher competence is
      considered to be of strategic importance to the quality of education for nurses,
      and nurse educators are expected to have a doctorate or master's degree in
      nursing or social science. This article focuses on teaching competence as it is
      perceived by teachers and describes the strategies used by nurse educators to
      meet the educational changes. The data for this ethnographic study were collected
      by participant observations at three Swedish nursing schools and interviews with
      59 nurse educators. Results indicate that nurse educators use three different
      strategies to cope with changing demands and to keep their knowledge and
      competence as faculty at a desirable level. A good nurse educator must: (a) be a
      "real" nurse; (b) be well prepared in different subject matters; or (c) have an
      academic degree (master's degree or PhD). The success of the change from
      vocational training of nurses to an academic education depends on the faculty
      composition and the culture of the school. As a result of the increased demands
      for competence, traditional strategies to cope with change are no longer
      appropriate. Nonacademic-educated faculty risk losing their identity as good
      educators.

PMID- 9921787
TI  - The impact of an HIV/AIDS training course for baccalaureate nursing students.
AB  - This study focuses on the impact of a specialized course to train baccalaureate
      nursing students to work with individuals with HIV disease. The overall goals of
      the course were to increase general and specific knowledge while improving
      beliefs regarding individuals with HIV disease. The course outline included
      components to increase knowledge in the areas of epidemiology, medical
      considerations, treatment, ethical and legal issues, and psychosocial issues.
      Pretests and posttests were given to participants and to a comparison group which
      had not received educational training. Results indicated the training
      significantly increased HIV/AIDS knowledge, and participants reported more
      positive beliefs about individuals with HIV disease.

PMID- 9921788
TI  - Concept maps: a strategy to teach and evaluate critical thinking.
AB  - The purpose of this article is to describe a study that implemented concept maps
      as a methodology to teach and evaluate critical thinking. Students in six senior
      clinical groups were taught to use concept maps. Students created three concept
      maps over the course of the semester. Data analysis demonstrated a group mean
      score of 40.38 on the first concept map and 135.55 on the final concept map, for
      a difference of 98.16. The paired t value comparing the first concept map to the
      final concept map was -5.69. The data indicated a statistically significant
      difference between the first and final maps. This difference is indicative of the
      students' increase in conceptual and critical thinking.

PMID- 9921789
TI  - Intercellular adhesion molecule-1 expression in endothelial cells is activated by
      cytomegalovirus immediate early proteins.

PMID- 9921790
TI  - Characterization of human xenoreactive antibodies in liver failure patients
      exposed to pig hepatocytes after bioartificial liver treatment: an ex vivo model
      of pig to human xenotransplantation.
AB  - BACKGROUND: There are limited experimental data on the nature of the humoral
      response elicited in humans against pig antigens. In this study, we have examined
      the xenoantibody (XAb) response in eight patients with acute liver failure
      exposed to pig hepatocytes after treatment with the bioartificial liver (BAL).
      METHODS: Patients' plasma samples obtained before and after BAL treatment were
      tested for IgM and IgG XAbs, IgG subclasses, and XAb cytotoxicity, using enzyme
      linked immunosorbent assay and flow-cytometric assays. The characterization of
      pig aortic endothelial cell (PAEC) surface xenoantigens was analyzed by
      immunoprecipitation. RESULTS: We observed by day 10, a strong anti-pig IgG and
      IgM XAb response in patients undergoing two or more BAL treatments, with a
      significant increase in all the IgG subclasses; in contrast, XAb titers did not
      change if the patients received only one BAL treatment. The majority of the XAbs
      produced to porcine antigens were primarily specific for the alphaGal epitope.
      Both IgG and IgM XAbs were cytotoxic to PAECs, and the cytotoxic activity of IgG
      was associated with high levels of IgG1 and IgG3 subclasses, known to be
      efficient on complement activation. The characterization of porcine surface
      antigens demonstrated that IgM human XAbs, before and after BAL exposure,
      recognized xenoantigens on PAECs with similar molecular weights, suggesting that
      the same population of XAbs were present in the patients before and after
      exposure to pig antigens. CONCLUSIONS: Repetitive exposure of humans to porcine
      antigens after BAL treatment, results in a strong IgG and IgM XAb responses that
      are primarily directed against the alphaGal epitope. These XAbs are cytotoxic to
      PAECs and the IgG toxicity correlates with high IgG1 and IgG3 levels. Our data
      also suggest that no new XAb specificity emerges after porcine exposure.

PMID- 9921792
TI  - HLA-G expression protects porcine endothelial cells against natural killer cell
      mediated xenogeneic cytotoxicity.
AB  - BACKGROUND: Natural killer (NK) cells are major component of the cellular
      response in xenotransplantation. NK cell activation and NK cell-mediated
      cytotoxicity can be a direct barrier to the potential use of xenogeneic organs in
      human transplantation. METHODS: To determine if HLA-G would protect porcine
      xenogeneic cells from human NK cell lysis, human full-length HLA-G genomic DNA
      was transfected into porcine aortic endothelial cell (PAECs) by the lipofection
      method. Surface expression of HLA-G in transfected PAECs was confirmed by
      immunofluorescense staining with anti-HLA class I framework antibody, PA2.6.
      Fresh human peripheral blood lymphocytes were used as NK effector cells with HLA
      G-transfected PAECs as targets in a 51Cr release assay. The inhibition of human
      polyclonal NK cells by HLA-G expression on PAECs was confirmed by antibody
      blocking using purified F(ab')2 portion of anti-human HLA class I antibody PA2.6.
      RESULTS: Expression of HLA-G on PAECs conferred a significant protection against
      NK-mediated lysis (range: 52-100% inhibition) when peripheral blood lymphocytes
      from seven healthy donors, bearing either homozygous HLA-Cw3 or -Cw4 used as NK
      effector cells. Such protection was inhibited by purified F(ab')2 portion of anti
      HLA class I antibody, indicating that the protection of PAECs was directly
      mediated by HLA-G expression. CONCLUSIONS: Expression of HLA-G on PAECs protected
      xenogeneic PAECs against human polyclonal NK cell-mediated lysis. These results
      indicate that the expression of HLA-G alone in the absence of other nonclassical
      HLA class I molecules is sufficient to inhibit human NK cell lysis. These
      findings suggest methods utilizing HLA-G to overcome NK cell-mediated
      cytotoxicity against porcine endothelial cells, considered the first cell type
      effected during xenograft cellular rejection.

PMID- 9921791
TI  - Porcine kidney and heart transplantation in baboons undergoing a tolerance
      induction regimen and antibody adsorption.
AB  - BACKGROUND: Xenotransplantation would provide a solution to the current shortage
      of organs for transplantation. Our group has been successful in inducing
      tolerance in mice and monkey models of allogeneic transplantation. The present
      study attempts to extend the same tolerance-inducing regimen to a pig-to-baboon
      organ transplantation model. METHODS: Nine baboons underwent a conditioning
      regimen (consisting of nonmyeloablative or myeloablative whole body and thymic
      irradiation, splenectomy, antithymocyte globulin, pharmacologic immunosuppression
      and porcine bone marrow transplantation [BMTx]), which has previously been
      demonstrated to induce donor-specific allograft tolerance in monkeys. In
      addition, immunoadsorption of anti-alphaGal antibody (Ab) was performed. Four of
      the nine baboons received pig kidney transplants (KTx), and one also underwent
      repeat transplantation with an SLA-matched kidney. Two received heterotopic pig
      heart transplants (HTx). Three baboons underwent conditioning without organ
      transplantation for long-term studies of natural Ab kinetics. RESULTS: In the
      three baboons that received the conditioning regimen without an organ transplant,
      immunoadsorption reduced Ab by approximately 90%, but recovery of Ab to
      pretreatment level or higher occurred within 7 days. In contrast, the level of Ab
      remained low after organ transplant. No Ab to pig antigens other than alphaGal
      was detected in any baboon before or after BMTx, KTx, or HTx. No graft succumbed
      to hyperacute rejection. KTx function began to deteriorate within 3-6 days, with
      oliguria and hematuria progressing to anuria, and the kidneys were excised after
      3, 6, 9, 11, and 14 days, respectively. One HTx ceased functioning at 8 days; the
      second baboon died with a contracting HTx at 15 days. Features of coagulopathy
      and thrombocytopenia developed in all six transplanted baboons (high D-dimer,
      prolonged prothrombin time and partial thromboplastin time, and falling
      fibrinogen) resulting in serious bleeding complications in two baboons, one of
      which died on day 9. Donor organs showed progressive acute humoral rejection with
      deposits of IgM, IgG, and complement; a focal mononuclear cellular infiltrate was
      also observed. The ureter was the earliest structure of the KTx affected by
      rejection, with progression to necrosis. CONCLUSIONS: This conditioning regimen
      prevented hyperacute rejection but was ineffective in preventing the return of
      Ab, which was associated with the development of acute humoral rejection with
      features of coagulopathy. No baboon developed anti-pig Ab other than alphaGal Ab.
      Further modifications of the protocol directed toward suppression of production
      of Ab are required to successfully induce tolerance to pig organs in baboons.

PMID- 9921793
TI  - Use of von Willebrand diseased kidney as donor in a pig-to-primate model of
      xenotransplantation.
AB  - BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection
      is essential and depends upon platelet adhesion and aggregation. The initial
      binding of platelets to the damaged endothelium is due to the interaction of the
      platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is
      present on activated endothelial cells and bound to the subendothelial matrix. We
      hypothesized that the use of organs from animals with homozygous von Willebrand
      disease (vWD), severely deficient in vWF, might prevent the thrombosis
      encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by
      extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through
      the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD
      or control pig kidney xenografts. XNA levels, coagulation, and platelet
      activation markers were studied, and specimens of rejected kidneys were analyzed
      histologically. RESULTS: Although XNA depletion was comparable in both groups,
      neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine
      kidneys showed any difference. Platelet and coagulation activation was evidenced
      in both groups after surgery and at rejection time. Immunohistochemical analysis
      revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys,
      whereas it was undetectable in the nongrafted vWD kidneys, suggesting the
      deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of
      vWD organs did not improve the survival time of grafted kidneys in this
      xenotransplantation model. Further studies on the use of vWD organs, in
      association with other therapeutic approaches, such as complement inhibition, are
      nevertheless necessary to evaluate the usefulness of vWF deficiency as an
      adjunctive therapy to decrease the coagulation process during xenograft
      rejection.

PMID- 9921794
TI  - The effect of tissue factor pathway inhibitor on hepatic ischemic reperfusion
      injury of the rat.
AB  - BACKGROUND: Tissue factor (TF) is an initiation factor for blood coagulation, and
      its expression is induced on macrophages and endothelial cells during the
      inflammatory or immune responses. In a previous study, we reported the
      significance of TF expression in hepatic ischemic reperfusion injury using a rat
      model. Recently, tissue factor pathway inhibitor (TFPI) has been discovered, and
      the effect of TFPI has been assessed in vivo. In this study, therefore, we
      studied the effect of TFPI on hepatic ischemic reperfusion injury of the rat.
      METHODS: After laparotomy of Lewis rats, the branches of the hepatic artery and
      portal vein leading to the median, left, and caudate lobes of the liver were
      clamped. The liver was reperfused after 120 or 180 min of ischemia.
      Simultaneously, recombinant human TFPI (4 mg/kg) was injected via a
      superiomesenteric vein. Rats were sacrificed at 5, 12, and 24 hr after
      reperfusion, and liver tissues were harvested. TF expression was studied by
      immunohistochemical staining with the monoclonal antibody (HTF-K108). RESULTS:
      Survival rates over a 5-day period were examined after the ischemic time of 120
      and 180 min. Seven of 10 rats in the 120-min ischemia group (n=10), and only 1
      (10%) rat of 10 in the 180-min ischemia group (n=10) survived. However, by the
      treatment with TFPI, all of the rats in the 120-min ischemia group (n=10), and
      six rats in the 180-min ischemia group (n=10) survived (P<0.05). The serum
      concentrations of alanine aminotransferase (ALT) and thrombin-antithrombin
      complex (TAT) before ischemia were 30.0+/-2.3 IU/L and 4.7+/-1.4 ng/ml,
      respectively (n=5). These levels showed a peak at 3-5 hr after reperfusion (ALT:
      13909+/-1900 IU/L, TAT: 30.4+/-7.0 ng/ml) (P<0.01). However, both peak levels
      were decreased by the treatment with TFPI (ALT: 6017+/-1290 IU/L, TAT: 5.4+/-2.1
      ng/ml) (P<0.01). Although TF was strongly stained on endothelial cells and
      Kupffer cells accumulating to the site of the necrosis in the control group, the
      area of the necrosis and the grade of TF staining were significantly reduced in
      the TFPI-treated group. CONCLUSIONS: These results indicated that TFPI strongly
      inhibited the injury of the ischemic reperfusion, and confirmed that TF played a
      pivotal role in the development of ischemic reperfusion injury.

PMID- 9921795
TI  - Unbound cyclosporine and allograft rejection after heart transplantation.
AB  - BACKGROUND: To determine the impact of cyclosporine plasma protein binding on
      organ rejection after cardiac transplantation, the incidence of cardiac rejection
      episodes was compared among patients who had differing levels of cyclosporine
      plasma fraction unbound (fU). METHODS: Forty-six consecutive cardiac transplant
      recipients were sampled at 1, 3, 6, and 12 months after transplantation, and
      cyclosporine plasma fU was determined, using a specially developed equilibrium
      dialysis method. At the completion of the study, incidences of cardiac rejection
      episodes were compared among patients having mean cyclosporine fU (Csfu) that
      were low (LCsfu; mean+/-SD, 1.33+/-0.10%, n=15), intermediate (ICsfu; 1.60+/
      0.07%, n= 16), and high (HCsfu; 1.99+/-0.30%, n=15). RESULTS: Percentage of
      endomyocardial biopsies (grade 3a, 3b, and 4) with respect to the total number of
      biopsies performed in the first 3 months after transplant was significantly
      higher in the LCsfu group than the other groups (40.9% in LCsfu vs. 28.5% for
      ICsfu and 32.1% for HCsfu groups, P=0.02). The linearized rate of rejection
      (episodes of rejection/100 patient-days) in the first month after transplant was
      6.5+/-1.7 for LCsfu, 3.5+/-0.8 for ICsfu and 4.3+/-0.9 for the HCsfu group
      (P<0.05, low vs. intermediate-high). The mean (95% confidence interval) of time
      interval between the first and second episodes of rejections was 10.7 (5.6-16.0)
      days for LCsfu, 18.0 (8.6-29.0) days for the ICsfu, and 26.0 (15.1-36.9) days for
      the HCsfu group (P<0.01). The total number of rejections requiring treatment per
      patient in the first 3 months after transplant was higher in the LCsfu group
      compared with the others (4.0+/-1.7 episodes for LCsfu vs. 2.9+/-1.1 for ICsfu
      and 3.2+/-1.2 episodes for HCsfu; P<0.05). Four patients in the low group, one
      patient in the intermediate group, and no patients in the high group required
      treatment with total lymphoid irradiation (P<0.02). CONCLUSIONS: This finding
      suggests that patients with lower levels of cyclosporine fU are more prone to
      cardiac rejection and that the level of cyclosporine fraction unbound may be
      clinically important for determination of response to cyclosporine therapy.

PMID- 9921796
TI  - Serum transforming growth factor-beta1 levels in bone marrow transplant
      recipients correlate with blood cell counts and chronic graft-versus-host
      disease.
AB  - OBJECTIVE: Profound immunosuppression and extensive fibrotic changes in the skin
      are characteristic for graft-versus-host disease (GVHD) after allogeneic bone
      marrow transplantation (BMT). Transforming growth factor (TGF)-beta is a potent
      immunosuppressive cytokine that plays an important regulatory role in the immune
      response. In addition, TGF-beta promotes wound repair but has also been
      implicated in tissue fibrosis. These characteristics prompted us to question
      whether serum TGF-beta levels would be associated with GVHD after BMT. METHODS:
      In this study, total TGF-beta1 levels in serum from HLA-identical BMT recipients
      before and at several time intervals after transplantation were quantified and
      correlated with platelet and white blood cell (WBC) counts and with the presence
      of acute and chronic GVHD in a multivariate analysis. RESULTS: TGF-beta1 levels
      were readily detectable in healthy controls and in BMT recipients before BMT. In
      all patients, a rapid drop in TGF-beta1 levels was seen during the BMT
      conditioning regimen. After 20-50 days postBMT, TGF-beta1 levels started to
      increase to normal levels. Platelet and WBC counts were strongly correlated with
      TGF-beta1 levels (r=0.810, P<0.001, and r=0.733, P<0.001, respectively).
      Multivariate analysis also revealed that TGF-beta1 levels were significantly
      increased during chronic GVHD and that the increase during acute GVHD reached
      levels of significance (P=0.009 and P=0.053, respectively). CONCLUSIONS: These
      results show that total TGF-beta1 levels correlate significantly with platelet
      and WBC counts and that chronic GVHD is associated with an increase in serum TGF
      beta1, independent of platelet or WBC counts.

PMID- 9921797
TI  - Hepatic sickling: an unusual cause of liver allograft dysfunction.
AB  - Orthotopic liver transplantation can be performed successfully in thalassemia. In
      this article, we describe a case of liver transplantation in a patient with
      sickle cell/beta-thalassemia complicated by liver sickling. Intrahepatic sickling
      must be considered in case of allograft dysfunction. This condition can easily be
      diagnosed by biochemical investigation and liver ultrasonography.

PMID- 9921798
TI  - Quality of life, functional status, and depression in male liver transplant
      recipients with recurrent viral hepatitis C.
AB  - BACKGROUND: The quality of life, psychologic sequelae, and functional status of
      liver transplant recipients with recurrent hepatitis C virus (HCV) hepatitis have
      not been well defined. METHODS: Perceived quality of life, psychologic distress,
      depression, adaptive coping, and functional status were prospectively assessed in
      59 liver transplant recipients at baseline (before transplantation) and 6 and 12
      months after transplantation; comparisons were made between patients with
      recurrent HCV hepatitis and all other patients. RESULTS: Recurrent HCV hepatitis
      developed in 41% (14/34) of the patients with HCV. At 6 months, the patients with
      recurrent HCV hepatitis had significantly lower functional status (P=0.013) and
      experienced less gain in physical functioning from baseline than other patients
      (P=0.02). Quality of life, depression, and psychologic distress were not
      different at 6 months for patients with recurrent HCV hepatitis compared with all
      other patients. At 12 months, the patients with recurrent HCV hepatitis had
      significantly lower quality of life (P=0.003), greater depression (P=0.045),
      higher psychologic distress (P=0.05), and lower physical functioning (P=0.008)
      than all other patients. CONCLUSION: Recurrent HCV hepatitis in liver transplant
      recipients is associated with impairment in quality of life, functional status,
      and greater depression compared with patients who did not have HCV and those
      without HCV recurrence.

PMID- 9921799
TI  - Applicability of living donor liver transplantation to high-urgency patients.
AB  - BACKGROUND: Cadaveric liver donors are scarce in Hong Kong, and the application
      of liver transplantation to high-urgency patients is limited. We evaluated the
      use of grafts from living donors in this setting. METHODS: From July 1994 to
      January 1998, 49 consecutive adult patients who were intensive care unit-bound
      because of acute or chronic liver failure were put on a high-urgency list for
      liver transplantation. Family members were not solicited for living donation, and
      the initiation and decision for living donor liver transplantation (LDLT) was
      based on the donor's voluntary intent. Assessment of the living donor, including
      blood tests, computed tomographic volumetry, and angiography, was performed only
      after informed consent was executed. RESULTS: In 25 of 49 (51%) patients, no
      family member volunteered as living donor; 23 died awaiting donor organs, and 2
      received a cadaveric graft. Twenty-four (49%) patients had 36 family members who
      volunteered as living donors. Before evaluation of living donor was completed,
      two patients received a cadaveric liver transplant. LDLT was not performed in
      nine patients because of recipient contraindications (n=4), ABO blood group
      incompatibility (n=3), and withdrawal of donor (n=2). Eight of these nine
      patients died, and one received a cadaveric liver graft. The remaining 13 (27%)
      patients received grafts from living donors. Four of 5 (80%) patients who
      underwent cadaveric liver transplantation and 11 of 13 (85%) who underwent LDLT
      survived. Thus, emergency transplantation from living donors increased the
      applicability of liver transplantation from 10% to 37%, and the survival rate
      after emergency LDLT (85%) was superior to that of the remaining patients (11%).
      CONCLUSIONS: When cadaveric organ donation is scarce, emergency liver
      transplantation from living donors can be applied to high-urgency adult patients.

PMID- 9921800
TI  - Antibodies to hepatitis C virus envelope proteins correlate with hepatitis C
      viraemia after liver transplantation.
AB  - BACKGROUND: Liver transplant recipients for hepatitis C virus (HCV)-related
      cirrhosis usually remain anti-HCV-seropositive after transplantation. The aim of
      this study was to characterize, longitudinally, the profile of HCV-specific
      antibodies and cryoglobulins in liver transplant recipients with recurrent HCV
      infection. METHODS: Serial serum samples were collected prospectively before, at
      1 month after, and at 12 months after transplantation for HCV cirrhosis in 30
      patients infected with genotype 1. The antibodies against HCV envelope proteins
      (E1 and E2) were quantitated by enzyme-linked immunosorbent assay and antibodies
      against core, E2/hypervariable region I (HVRI), NS3, NS4, and NS5A antigens by a
      line immunoassay. Sera were also tested for cryoglobulins. RESULTS: The titer of
      each anti-HCV antibody had fallen at 1 month after transplantation (P<0.05) with
      the exception of anti-E1 levels, which had risen in 16 patients with acute
      hepatitis C at that time (P=0.01). Anti-E1 and anti-E2 titers, but not antibodies
      against other HCV antigens, increased to pre-transplantation levels or higher at
      12 months, which correlated with serum HCV RNA levels. Cryoglobulinemia was
      present in nine patients after transplantation (30%) and was associated with
      lower anti-E1 levels (P=0.04) and more severe graft damage. CONCLUSIONS: The
      early increase in antibodies to HCV envelope proteins in correlation with viremia
      suggests that the envelope-specific humoral immune response may be directly
      stimulated by HCV replication. Anti-E1 levels may be a useful marker in
      monitoring patients with recurrent HCV infection.

PMID- 9921801
TI  - Clinical significance of renal biopsies showing concurrent acute rejection and
      tacrolimus-associated tubular vacuolization.
AB  - BACKGROUND: The clinical significance of biopsies showing both rejection and
      isometric tubular vacuolization has not been well defined in the literature.
      METHODS: The clinical picture, sequential histopathologic findings, and response
      to therapy were compared between 24 renal allograft biopsies showing both tubular
      vacuolization and rejection and 14 biopsies showing vacuolization alone. RESULTS:
      The rejection was categorized as grade 1 in 4/24 (16.6%), grade 2A in 10/24
      (41.6%), and grade 2B in 10/24 (41.6%) cases (Banff schema, 1993-1995). Treatment
      with additional steroids and tacrolimus led to a decrease in the interstitial
      inflammation score (2.6+/-0.1 to 1.3+/-0.1, P<0.001), tubulitis score (2.6+/-0.1
      to 1.1+/-0.1, P<0.001), and serum creatinine (4.4+/-2.2 mg/dl to 3.3+/-2.6 mg/dl,
      P=0.001). Complete response, partial response and no response to antirejection
      therapy were observed in 16/24 (66.7%), 3/24 (12.5%), and 5/24 (20.8%) patients,
      respectively. Although there was a rise in the plasma (1.4+/-0.2 ng/ml to 2.8+/
      0.3 ng/ml, P<0.001) and whole blood (16.5+/-2.8 ng/ml to 31.2+/-5.7 ng/ml,
      P<0.001) tacrolimus levels, repeat biopsy showed no change in the size or extent
      of tubular vacuolization (mean score 2.88+/-0.19 vs. 2.83+/-0.21). The
      morphologic characteristics of the tubular vacuoles in these cases did not differ
      from those observed in 14 cases of tacrolimus nephrotoxicity not complicated by
      rejection. CONCLUSION: Patients with concurrent acute rejection and tubular
      vacuolization usually benefit from increased immunosuppression. The pathogenesis
      of the vacuolization in this clinical setting is not clear, but may reflect
      immune-mediated tubular injury.

PMID- 9921802
TI  - Prevalence and clinical significance of antiphospholipid antibodies in renal
      transplant recipients.
AB  - BACKGROUND: The prevalence and clinical significance of antiphospholipid
      antibodies (APAs) have not been extensively studied in non-systemic lupus
      erythematosus (non-SLE) renal transplant recipients. METHODS: To further define
      the prevalence and clinical significance of APAs in non-SLE renal transplant
      recipients and the appearance of dialysis-related APAs after renal
      transplantation, we conducted a retrospective study on 178 renal transplant
      recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus
      anticoagulant in non-SLE renal transplant recipients, retrospective documentation
      of ACAs on pretransplant frozen plasma and standardized collection of demographic
      characteristics and posttransplant history of thrombosis were assessed. RESULTS:
      Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and
      hemodialysis duration was longer in patients with APAs. A posttransplant history
      of both venous and arterial thrombosis was more frequent in patients with
      posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3%
      [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients
      with posttransplant ACAs had ACAs in the pretransplant period (85%).
      Pretransplant ACAs were associated with a posttransplant history of venous
      thrombosis (P<0.001). CONCLUSIONS: Our study demonstrates a high prevalence of
      APAs in non-SLE renal transplant recipients. Most of them have been acquired in
      the pretransplant period. Both pretransplant ACAs and posttransplant APAs are
      associated with posttransplant episodes of thrombosis. Further studies are
      required to determine the interest of prophylactic measures.

PMID- 9921803
TI  - Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and
      kidney-pancreas transplant recipients.
AB  - BACKGROUND: With the introduction of ganciclovir, the clinical pattern of
      cytomegalovirus (CMV) disease has changed; CMV disease recurrence after
      successful treatment of the initial episode has emerged as a more common problem.
      We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous
      kidney-pancreas transplant (SPK) recipients, and identified risk factors for
      recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287
      SPK recipients, 332 developed CMV disease and were treated with a 14-day course
      of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these
      332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days
      after treatment for the initial episode; this group was compared with those
      recipients who did not develop recurrence (n=229). Risk factors examined were
      age, presence of diabetes, type of transplant (KTx vs. SPK), donor source
      (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV
      serologic status, evidence of tissue-invasive CMV, and treatment of the initial
      episode with human immune globulin in addition to ganciclovir. RESULTS:
      Univariate analysis found that patients with recurrence were more likely to be
      diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%;
      P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to
      have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using
      multivariate analysis, two statistically significant risk factors were found:
      receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for
      acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK
      transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the
      difference did not reach statistical significance. The remaining variables were
      not significant. Interestingly, CMV recurrence did not significantly diminish 5
      year graft survival (52.0% vs. 54.4%; P not significant) or patient survival
      (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in
      roughly one-third of KTx and SPK recipients after treatment of the initial
      episode with ganciclovir. A cadaver organ source and treatment for acute
      rejection were the most significant clinical risk factors for recurrence.
      Clinical predictors of recurrence such as these may help to identify those
      recipients who need more intensive therapeutic and prophylactic regimens.

PMID- 9921804
TI  - The clinical significance of cytomegaloviral inclusions in the allograft kidney.
AB  - BACKGROUND: Renal allografts are a frequent site of subclinical cytomegalovirus
      (CMV) infection diagnosed by culture, but histologic inclusions occur in less
      than 1% of biopsies. The natural history of this subgroup of patients has been
      reported only occasionally, mostly before the availability of ganciclovir
      therapy. METHODS: We analyzed the clinical parameters and pathologic findings in
      10 patients with CMV inclusions at allograft biopsy. RESULTS: The patients were
      29-72 years old, and 9 of 10 (90%) had previous episodes of acute rejection, 3 of
      whom needed OKT3 administration. Histopathologic examination of the allografts
      showed interstitial inflammation with tubulitis in 7 of 10 (70%) patients; in 3
      of 10 (30%) patients, viral inclusions were present in the glomerular capillary
      endothelia without any associated inflammatory response. Morphologic criteria for
      acute transplant glomerulopathy or proliferative glomerulonephritis were not
      satisfied. Extrarenal viral inclusions were documented in the gastrointestinal
      tracts of 2 of 10 (20%) patients. The patients were treated with reduced
      immunosuppression and ganciclovir. Five patients lost their grafts 56.6+/-86.6
      days (range, 4-210 days; median, 21 days) after initial diagnosis. The serum
      creatinine in the remaining five patients was 3.3+/-2.0 mg/dl (range, 1.2-6.5
      mg/dl; median, 2.5 mg/dl) 77+/-16 days (range, 56-101 days; median, 77 days)
      after transplantation. Histopathologic examination showed no residual viral
      inclusions in 5 of 7 (71.4%) follow-up specimens available for examination.
      CONCLUSIONS: CMV inclusions in renal allograft biopsies typically occur after
      treatment for rejection. Ganciclovir eradicates replicative virus, but graft
      outcome is determined by coexisting acute rejection and chronic allograft
      nephropathy. Graft loss primarily attributable to CMV was not observed.

PMID- 9921805
TI  - Human polyoma virus-associated interstitial nephritis in the allograft kidney.
AB  - BACKGROUND: Asymptomatic polyoma virus infection documented by urine cytology or
      serology is well known, but the clinical course of biopsy-proven interstitial
      nephritis is not well defined. METHODS: Twenty-two cases were identified by
      histology, immunostaining, in situ hybridization, electron microscopy, or
      polymerase chain reaction. RESULTS: The clinical features mimicked acute
      rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy
      (n=2), or drug toxicity (n=1). Histology showed homogenous intranuclear
      inclusions. In situ hybridization showed BK virus (BKV) to be the predominant
      species, but polymerase chain reaction documented JC virus co-infection in one of
      five cases so tested. Electron microscopy in seven cases showed 20-51-nm virions.
      The two cases diagnosed at nephrectomy received no therapy. Initial antirejection
      therapy in 12 cases led to clearance of the virus in 1/12 (8%), partial
      therapeutic response in 3/12 (25%), and graft loss in 8/12 (67%) cases. The last
      recorded creatinine in patients with functional grafts ranged from 1.9 to 7.0
      (median: 4.5) mg/dl, 0.4-45 (median: 4.0) months after initial diagnosis. The
      remaining eight cases treated by reduction of immunosuppression at the outset
      have been free of graft loss for 0.2-10.0 (median: 4.8) months since diagnosis,
      and clearance of virus has been documented in three of six (50%) cases. The serum
      creatinine in these patients is 1.7-6.0 (median: 2.4) mg/dl, 0.2-10 (median: 4.8)
      months after diagnosis. Follow-up biopsies performed 1-23.5 months after
      diagnosis show chronic allograft nephropathy. CONCLUSIONS: Polyoma virus tubulo
      interstitial nephritis-associated graft dysfunction usually calls for judicious
      decrease in immunosuppression and monitoring for acute rejection. Development of
      methods to serially quantify the viral load in individual patients could
      potentially improve clinical outcome.

PMID- 9921806
TI  - Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double
      Therapy Study Group.
AB  - BACKGROUND: Acute rejection is still a major problem in renal transplantation and
      is one of the most important causes of chronic graft dysfunction and late graft
      loss. Selective immunosuppression with a humanized antibody against the alpha
      chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the
      efficacy of this type of immunoprophylaxis in combination with dual
      immunosuppression. METHODS: We studied the effect of daclizumab, a humanized
      monoclonal antibody against the alpha-chain of the IL-2 receptor, in a randomized
      double-blind, prospective phase III clinical trial in 275 patients receiving a
      first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116
      (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg)
      every other week. Baseline immunosuppression consisted of cyclosporine and
      corticosteroids. RESULTS: At 6 months, 39 (28%) of the patients in the daclizumab
      group had biopsy-proven rejections, as compared with 63 (47%) in the placebo
      group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte
      globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the
      daclizumab group (8% vs. 16%, P=0.02), and they required significantly lower mean
      (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the
      placebo group, P=0.01). Graft function was significantly better (P=0.02) in the
      daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient
      survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in
      daclizumab-treated patients. Patients receiving daclizumab experienced fewer
      cytomegalovirus infections (18% vs. 25%), and none died from severe infectious
      complications, compared to four patients in the placebo arm. No patient in the
      daclizumab group had a lymphoproliferative disorder or any other form of
      immunosuppression-related tumor during the first year after transplant.
      CONCLUSIONS: Administration of daclizumab in addition to dual immunosuppression
      therapy significantly reduced biopsy-proven acute rejection after renal
      transplantation, improved patient survival, and did not add to the toxicity of
      the immunosuppressive regimen.

PMID- 9921807
TI  - Enhanced hepatocyte growth factor expression associated with prolonged rat
      hepatic allograft survival in recipients pretreated with donor-specific blood.
AB  - BACKGROUND: Pretransplantation injection of freshly heparinized donor blood
      (donor-specific blood transfusion, or DST) significantly prolongs the survival of
      hepatic allografts from ACI(RT1a) to LEW(RT1l) rats. We investigated hepatocyte
      growth factor (HGF) expression in rat hepatic allografts of recipients pretreated
      with or without DST. METHODS: The levels of HGF mRNA and protein in hepatic
      allografts were determined after transplantation. The localization of HGF+ cells
      was identified with a rat anti-HGF monoclonal antibody. RESULTS: Plasma HGF
      concentrations in transplanted rats treated with DST were significantly and
      persistently increased compared to untreated rats with hepatic allografts. The
      number of HGF+ cells in hepatic allografts of recipients pretreated with DST on
      day 14 was significantly greater than that in allografts of untreated recipients
      on day 7. HGF+ cells were also found in the marginal zone and red pulp of
      recipient spleens. Northern blot analysis revealed the presence of three HGF+
      cell phenotypes: HGF+ED1+, HGF+ED2+, and HGF+ED1-ED2-. Most HGF+ cells were ED1
      ED2-. In situ hybridization demonstrated HGF mRNA in the mononuclear cells in the
      portal and sinusoidal areas as well as the marginal zone and red pulp in both DST
      treated and untreated recipient spleens. CONCLUSIONS: Enhanced HGF expression in
      rat hepatic allografts is associated with immunologic unresponsiveness induced by
      DST.

PMID- 9921808
TI  - Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear
      cell preparations.
AB  - BACKGROUND: T cells present in an allogeneic bone marrow transplant may produce
      graft-versus-host disease but also contribute to immune reconstitution and
      enhance engraftment. Our aim was to separate alloreactive from nonalloreactive T
      lymphocytes, by performing a mixed lymphocyte culture (MLC) stimulation of donor
      cells, followed by selective depletion of activated cells expressing the high
      affinity interleukin 2 receptor. We then characterized the resulting depleted
      cell fraction. METHODS: Donor peripheral blood mononuclear cells were cocultured
      with irradiated peripheral blood mononuclear cells from HLA-nonidentical
      recipient stimulators in an MLC. After 3 days, CD25+ lymphocytes (alloreactive
      cells expressing the alpha chain of the interleukin 2 receptor) were removed by
      immunomagnetic separation. The depleted donor fraction and untreated cells were
      then rechallenged in a secondary MLC with the original irradiated stimulator
      cells or a third party to assess relative alloreactivity. RESULTS: Inhibition of
      the secondary MLC and of host-specific cytotoxic activities was observed as well
      as a disappearance of interleukin 2 receptor-positive cells. Alloreactivity
      against unrelated third-party cells was preserved. Limiting dilution analysis of
      residual alloantigen-reactive T lymphocytes demonstrated a 1.3 log reduction of
      antihost reactivity. The depletion largely removed host-specific alloreactive
      CD4+ cells. CONCLUSIONS: This method reduces alloreactivity while retaining
      reactivity against third-party targets. This approach may allow therapeutic
      infusion of T cells after HLA-nonidentical allografts with a reduced capacity to
      produce graft-versus-host disease.

PMID- 9921809
TI  - The role of CD8 and CD4 T cells in intestinal allograft rejection: a comparison
      of monoclonal antibody-treated and knockout mice.
AB  - BACKGROUND: The relative contribution of CD8 and CD4 T cells to allograft
      rejection remains an unresolved issue. Experimental results suggest that the
      relative importance of these T-cell subsets may vary depending on the model used
      and the organ studied. We have previously shown that treatment of murine
      recipients of intestinal allografts with a depleting anti-CD8 or a depleting anti
      CD4 monoclonal antibody (mAb) significantly inhibited allograft rejection. This
      study was undertaken to further examine the contribution of CD8 and CD4 T cells
      to the rejection of intestinal allografts. METHODS: Intestinal allografts from
      B6C3F1/J (C57BL/6 x C3H/HeJ) mice were transplanted into C57BL/6 recipients.
      Recipient groups included mice with an acquired deficiency in CD8 or CD4 T cells
      caused by treatment with depleting mAb or mice genetically deficient in CD8 or
      CD4 T cells as a result of disruption of the genes encoding major
      histocompatibility complex (MHC) class I, MHC class II, CD8, or CD4. In all
      cases, rejection was assessed histologically at predetermined time points. In
      some recipient groups, graft function was also assessed using a maltose
      absorption assay. RESULTS: Rejection, assessed between days 10 and 28 after
      transplantation, was significantly inhibited in mice deficient in CD8 or CD4 T
      cells after treatment with depleting mAb. In contrast, mice genetically deficient
      in either CD8 T cells (MHC class I or CD8 knockouts) or CD4 T cells (MHC class II
      or CD4 knockouts) rejected intestinal allografts promptly. Both histologic and
      functional evaluation of anti-CD8 mAb-treated mice on day 60 showed that the
      inhibition of rejection persisted even after the return of a substantial number
      of CD8 T cells. Although intestinal allografts from anti-CD8 mAb-treated mice
      displayed little to no evidence of rejection on day 60 after transplantation,
      these mice were able to reject both donor and third-party skin grafts.
      CONCLUSIONS: These results demonstrate that the inhibition of intestinal
      allograft rejection associated with mAb treatment is not attributable solely to
      depletion of CD8 or CD4 T cells. Furthermore, anti-CD8 mAb administration did not
      induce donor-specific tolerance or cause nonspecific immune suppression, as
      indicated by the skin-grafting experiments. Our findings suggest that at least
      some depleting mAbs mediate their protective effect on allograft rejection via an
      alternative mechanism such as the induction of a regulatory cell population(s).

PMID- 9921810
TI  - Intercellular adhesion molecule-1 expression in endothelial cells is activated by
      cytomegalovirus immediate early proteins.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with allograft
      vasculopathy and rejection. One potential mechanism is vascular injury from
      immunologically mediated processes. HCMV infection has been shown to increase the
      constitutive expression of intercellular adhesion molecule-1 (ICAM-1). The
      objective of this study was to determine the molecular basis of HCMV enhanced
      ICAM-1 gene expression in endothelial cells using human umbilical vein
      endothelial cells (HUVECs) as a model. METHODS: HUVECS were infected with HCMV
      virus and the level of ICAM-1 mRNA determined over time. HUVECS were then
      transiently transfected with plasmid constructs containing ICAM-1 and HCMV
      immediate early (IE) gene sequences and the effect of IE proteins on ICAM-1
      promoter expression determined. Antibodies to cytokines known to be affected by
      HCMV IE proteins or to modulate ICAM-1 expression were added to determine if
      cytokines were mediating ICAM-1 expression. RESULTS: Infection of HUVECs with
      HCMV resulted in a rapid rise in ICAM-1 mRNA levels, suggesting that the viral IE
      proteins were involved in gene activation. The HCMV IE1 and IE2 proteins
      synergistically activated both transfected and endogenous ICAM-1 gene expression.
      The addition of antibodies to interleukin-1, tumor necrosis factor-a,
      transforming growth factor-beta, or interleukin-6 had no effect on the IE protein
      mediated increase in ICAM-1 expression. Deletion analysis of the ICAM-1 gene
      promoter revealed that a minimum of 370 base pairs of 5' flanking sequences was
      required for maximal transactivation by IE proteins; mutation analysis showed
      that an NFkappaB site at base pairs -187 to -178 was not required for promoter
      activation. CONCLUSIONS: These results demonstrate that HCMV regulates the
      heterologous ICAM-1 gene promoter in endothelial cells not via cellular cytokine
      production, but rather by a direct effect of IE proteins, and supports a model in
      which HCMV IE gene products interact with ICAM-1 promoter elements to increase
      gene expression.

PMID- 9921811
TI  - Prophylaxis of acute renal allograft rejection using FTY720 in combination with
      subtherapeutic doses of cyclosporine.
AB  - BACKGROUND: In rodent transplant models, FTY720 exerts a synergistic affect with
      cyclosporine (CsA) to prolong allograft survival. The present experiments sought
      to test this combination in subhuman primates. METHODS: Cynomolgus monkeys were
      transplanted with kidney allografts that were incompatible in mixed lymphocyte
      culture reactions. The animals were treated with daily intramuscular injections
      of CsA using doses selected to maintain whole blood trough concentrations at
      therapeutic values between 40 and 200 ng/ml. The 4 experimental groups included
      CsA without or with 0.1, 0.3, or 1 mg/kg/day FTY720 delivered daily by
      intravenous bolus injection. Therapeutic effects were suggested both by the graft
      histology of biopsy within the first 10 posttransplant days and by the length of
      host survival. RESULTS: Whereas recipients treated with CsA alone rejected kidney
      allografts at a median survival time of 8.5 days (n=4), those treated with either
      0.1 or 0.3 mg/kg/day FTY720 in addition to CsA showed significant prolongation of
      kidney allograft survival to 71 days (n=3; P<0.04) or 63 days (n=5; P<0.05),
      respectively. The hosts in the 1.0 mg/kg/day FTY720 group survived 48 days, with
      2 of 5 recipients succumbing at 9 or 17 days postgraft, suggesting possible
      complications caused by overimmunosuppression. Biopsies of the 0.1 mg/kg/day
      FTY720 group on posttransplant day 7 documented mild to moderate rejection (grade
      I), indicated by multiple focal areas of tubular destruction. The histology
      results of transplants in the 0.3 or 1 mg/kg/day FTY720 group showed only minimal
      interstitial inflammatory infiltrates (borderline grade), with no evidence of
      tubular or arterial damage. Serum creatinine values among the animals in the 0.1
      mg/kg/day FTY720 group showed increases in 2 of 3 recipients by day 20 and in the
      third by day 41 postgraft. Among the 0.3 mg/kg/day FTY720 group, 3 of 5
      recipients maintained baseline creatinine values to 45 days postgraft; 1
      recipient had stable kidney function for 120 days postgraft. CONCLUSIONS:
      Addition of FTY720 therapy to a subtherapeutic CsA immunosuppressive regimen
      delays the rejection of renal allografts in subhuman primates.

PMID- 9921812
TI  - A comparison of the new preservation solution Celsior to Euro-Collins and
      University of Wisconsin solutions in lung reperfusion injury.
AB  - BACKGROUND: The lung is particularly susceptible to reperfusion injury, both
      experimentally and clinically after transplantation. The extracellular-type
      preservation solution Celsior, which has been predominantly studied in cardiac
      preservation, has components designed to prevent cell swelling, free radical
      injury, energy depletion, and calcium overload. Using an isolated blood-perfused
      rat lung model, we investigated whether Celsior would decrease preservation
      injury and improve lung function after cold ischemic storage and reperfusion
      compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions.
      METHODS: Lewis rat lungs were isolated, flushed with the respective cold
      preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After
      ischemic storage, the lung block was suspended from a force transducer,
      ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula
      in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference,
      and outflow oxygen tension were all measured. The capillary filtration
      coefficient (Kf), a sensitive measure of changes in microvascular permeability,
      was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had
      lower Kf values than those stored in EC, indicating decreased microvascular
      permeability. No other significant differences were noted between Celsior and EC
      or UW. For 12 hr of cold storage, Celsior provided increased oxygenation,
      decreased alveolar-arterial O2 differences, increased compliance, and decreased
      Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better
      lung preservation than EC or UW as demonstrated by increased oxygenation,
      decreased capillary permeability, and improved lung compliance, particularly at
      12-hr storage times. These results are highly relevant, inasmuch as EC and UW are
      the most common clinically used lung preservation solutions. Further studies of
      Celsior in experimental and clinical lung transplantation, as well as in other
      solid organs, are indicated.

PMID- 9921813
TI  - Evidence for heat shock protein immunity in a rat cardiac allograft model of
      chronic rejection.
AB  - BACKGROUND: The stress response to injury concept has been proposed as a
      mechanism of chronic rejection. This hypothesis has been tested with a rat
      cardiac allograft model in recipients pretreated with donor bone marrow (BM)
      cells. Chronic rejection is manifested in this BM group by obliterative
      arteriopathy and the epicardium and endocardium contains lymphocytic infiltrates
      resembling Quilty lesions. Pretreatment with a liver allograft (the orthotopic
      liver transplant [OLTx] group) is associated with an absence of chronic rejection
      in the transplanted heart. METHODS AND RESULTS: . Stress responses in the
      allograft were assessed by determining heat shock protein (hsp) expression by
      immunohistology of graft tissues and immunoblot analysis of stromal tissue
      lysates with monoclonal antibodies (mAb) to mammalian hsp60, the inducible hsp72,
      the constitutively expressed hsc73, and the grp78 C-terminal sequence KSEKDEL
      (grp78seq). Immunostaining showed clusters of grp78seq-positive cells in the
      inflammatory infiltrates of obliterated blood vessels and Quilty lesions in the
      BM group of cardiac allografts. Such grp78seq-positive cells were not seen in the
      OLTx group of heart allografts nor in syngrafts. Neither group showed
      significantly different graft myocyte staining of grp78 or hsp72, whereas hsp60
      and hsc73 showed higher expression in the BM group and, to a lesser extent, the
      OLTx group. The increased expression of hsc73 was seen especially in the
      obliterated arteries and in myocytes nearby cellular infiltrates. Immunoblot
      analysis of graft stromal tissue lysates showed additional bands with mAb to
      hsp60 and hsc73 for the OLTx and especially the BM group. No significant bands
      were seen for hsp72 and grp78. Lymphocytes isolated from chronically rejecting
      allografts reacted with irradiated autologous spleen cells in the presence of
      mycobacterial hsp65 and interleukin-2. Culturing of graft-infiltrating cells with
      mycobacterial hsp71 and interleukin-2 yielded lymphocyte clones without
      alloreactivity, but with strong proliferative responsiveness to self-antigen
      presenting cells and, only in the presence of mycobacterial hsp71 or murine
      grp78. This T-cell reactivity seemed to require intact hsp molecules because
      treatment of hsp71 with proteolytic enzymes, polymyxin, or ATP abrogated this
      induction of the stimulatory effect of self-antigen-presenting cells. These T
      cells are similar to the hsp-dependent, autoreactive lymphocytes cloned from
      acutely rejecting rat allografts. CONCLUSIONS: These findings support the concept
      that the pathogenesis of chronic rejection involves a stress response and the
      participation of graft-infiltrating autoreactive T cells that operate under hsp
      dependent mechanisms.

PMID- 9921814
TI  - Microchimerism in thymus is associated with up-regulated T helper type 1 cytokine
      transcription during cardiac allograft rejection in rats.
AB  - BACKGROUND: Intrathymic microchimerism (MC) is thought to be responsible for
      inducing allograft tolerance. However, the role of MC in the thymus gland after
      transplantation, particularly in the rejection response, is unknown. We
      investigated serial changes in intrathymic cytokine production associated with MC
      and allograft rejection. METHODS: Donor-specific cell injection (DSI) and
      heterotopic heart transplantation (HTx) were performed in the fully allogeneic
      combination using DA rats (RT1a) as donors and WS rats (RT1k)as recipients. MC
      was checked by polymerase chain reaction (PCR) using a donor RT1.Bbeta domain 1
      region sequence-specific primers. Reverse transcription (RT)-PCR analysis of
      cytokine (interleukin [IL]-2, interferon-gamma, IL-4, and IL-10) profiles of the
      thymus was performed in animals given DSI, HTx, or DSI/HTx. RESULTS: DSI alone
      resulted in an immediate development of MC, detected by PCR, in various organs
      including the thymus, spleen, liver, and blood, of most rats, lasting for over 2
      months. However, DSI-induced MC selectively disappeared in the thymus on day 7
      after grafting, several days before the rejection of cardiac allograft. RT-PCR
      analysis of cytokine profiles showed that the levels of Th1 (IL-2 and interferon
      gamma) cytokines transcribed in the thymus were higher than in the spleen. MC
      reappeared in the thymus on day 21 after grafting, but was not associated with
      elevation of Th1 cytokine transcription when allograft was replaced by fibrosis.
      CONCLUSIONS: Intrathymic MC does not always confer unresponsiveness to
      alloantigen, but can be eliminated after anti-donor response.

PMID- 9921816
TI  - Traumatic neuroma with biliary duct obstruction after orthotopic liver
      transplantation.
AB  - BACKGROUND: Traumatic neuromas may develop after injury to nerve fibers encased
      in Schwann cells. The incidence of symptomatic neural tumors appears to be low
      after orthotopic liver transplantation (OLT). Only two cases of biliary stricture
      caused by infiltrating traumatic neuroma have been described previously. METHODS:
      We report two new cases of biliary tract obstruction after OLT that failed to
      respond to percutaneous balloon dilatation and were corrected by a resection of
      the bile duct stricture followed by biliary reconstruction with a Roux-en-Y
      jejunal loop. RESULTS: The first patient (17 months after OLT) had a traumatic
      neuroma appearing as a distinct mass with nerve bundles confirmed histologically;
      the traumatic neuroma in the second patient (5 months after OLT) was a nerve
      stump with infiltration of nervous elements in the bile duct. Both patients
      recovered without complications. CONCLUSIONS: Traumatic neuromas should be
      considered in the differential diagnosis of late biliary stricture after OLT, in
      particular when not responding to percutaneous dilatation or stenting.

PMID- 9921815
TI  - Insulin and intracellular calcium responsiveness to glucagon-like peptide-1 and
      pituitary adenylate cyclase-activating peptide by dispersed adult porcine islet
      cells.
AB  - BACKGROUND: There is a great need to learn more about porcine islet physiology
      because porcine islets represent a promising source of xenogeneic tissue for beta
      cell replacement therapy in humans. METHODS: We evaluated the effects of two
      important physiological regulators of insulin secretion, glucagon-like peptide-1
      (GLP-1) and pituitary adenylate cyclase-activating peptide (PACAP), on insulin
      release and intracellular calcium ([Ca++]i) by adult porcine islet cells.
      RESULTS: Exposure to GLP-1 and PACAP significantly potentiated glucose-induced
      insulin release and improved the sensitivity to glucose as a secretagogue. About
      70% of cells stimulated with 20 mmol/L glucose alone showed an increase in
      [Ca++]i, whereas the addition of GLP-1 and PACAP induced [Ca++]i increases in 86%
      and 93% of cells, respectively. CONCLUSIONS: The good insulin and [Ca++]i
      responsiveness of porcine islet cells to both GLP-1 and PACAP provides an
      additional proof of their suitability for transplantation.

PMID- 9921817
TI  - Five cases of Kaposi's sarcoma in kidney graft recipients: possible influence of
      the immunosuppressive therapy.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is an human herpesvirus 8-associated tumor,
      occurring in immunocompromised patients. We report here an increased incidence of
      KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to
      the introduction of the immunosuppressant mycophenolate mofetil (MMF). METHODS: A
      total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the
      development of KS. A total of 371 patients received therapy including MMF (group
      A), whereas 1464 patients were treated with an MMF-free protocol (group B).
      RESULTS: 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group
      B developed KS. In group A, KS became evident 7+/-2 months after initiation of
      MMF therapy. CONCLUSIONS: At our center, during the last 2 years, the incidence
      of KS has increased in KGRs, and it is not clear whether the introduction of MMF
      contributes to the phenomenon.

PMID- 9921818
TI  - Management of acute right heart failure after combined heart and kidney
      transplantation: case report.
AB  - Combined heart and kidney transplantation is performed rarely and merits unique
      fluid-management considerations postoperatively. We present the case of a young
      man who developed acute right heart failure after combined heart and kidney
      transplantation and responded to hemofiltration. We believe that the
      postoperative management of combined heart and kidney transplant recipients
      should not be different from that of patients receiving a heart transplant only.
      Intravenous fluids should be administered judiciously, and hemofiltration should
      be instituted early to remove fluid and reduce preload if right heart failure
      develops.

PMID- 9921819
TI  - Subzero nonfreezing storage of isolated rat hepatocytes in University of
      Wisconsin solution.
AB  - BACKGROUND: Various cryopreservation techniques have been investigated to
      elongate preservation time, however, most have failed to be clinically induced
      because of damage due to ice crystal formation. Subzero nonfreezing conditions
      could theoretically reduce organ metabolism without damage due to ice crystal
      formation. We evaluated the superiority of subzero nonfreezing storage compared
      with conventional hypothermic storage using isolated rat hepatocytes stored in
      University of Wisconsin (UW) solution without cryoprotectants. METHODS:
      Hepatocytes of Wistar rats isolated by collagenase digestion were suspended in UW
      solution and divided into the following three groups: subzero nonfreezing group (
      4 degrees C), zero nonfreezing group (0 degrees C), and control group (4 degrees
      C). They were stored for 48 hr at the temperatures indicated. After 24 and 48 hr
      of storage, we carried out a trypan blue exclusion test and a 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and measured
      lactate dehydrogenase release, lactic acid, ATP content, and the ability of
      hepatocytes to synthesize urea. After 48 hr of storage, morphological differences
      between the control group and the subzero nonfreezing group were investigated by
      scanning and transmission electron microscopy. RESULTS: Significant improvements
      of the trypan blue exclusion test and ATP contents in the subzero nonfreezing
      group were observed. Lactic acid production was also significantly suppressed in
      the subzero nonfreezing group compared with that in the control group. The MTT
      assay value was significantly better at -4 degrees C than at 4 degrees C. The
      rate of urea synthesis at -4 degrees C was higher than that at 4 degrees C.
      Electron microscopy revealed that subzero nonfreezing delayed the lethal bleb
      forming process of stored hepatocytes, which was followed by mitochondrial
      swelling, compared with the control group. CONCLUSIONS: Subzero nonfreezing
      storage (-4 degrees C) in UW solution could provide better preservability for
      isolated rat hepatocytes with protection against hypoxic cell injury compared
      with conventional hypothermic storage (4 degrees C).

PMID- 9921820
TI  - Attachment of Escherichia coli O157:H7 to lettuce leaf surface and bacterial
      viability in response to chlorine treatment as demonstrated by using confocal
      scanning laser microscopy.
AB  - Confocal scanning laser microscopy was used to observe the location of
      Escherichia coli O157:H7 on and within lettuce leaves. Sections of leaves (ca.
      0.5 by 0.5 cm) were inoculated by submersion in a suspension of E. coli O157:H7
      (ca. 10(7) to 10(8) CFU/ml) overnight at 7 degrees C. Fluorescein isothiocyanate
      labeled antibody was used to visualize the attached bacteria. E. coli O157:H7 was
      found attached to the surface, trichomes, stomata, and cut edges. Three
      dimensional volume reconstruction of interior portions of leaves showed that E.
      coli O157:H7 was entrapped 20 to 100 microm below the surface in stomata and cut
      edges. Agar plate culturing and microscopic observation indicated that E. coli
      O157:H7 preferentially attached to cut edges, as opposed to the intact leaf
      surface. Dual staining with fluorescein isothiocyanate-labeled antibody and
      propidium iodide was used to determine viability of cells on artificially
      contaminated lettuce leaves after treatment with 20 mg/liter chlorine solution
      for 5 min. Many live cells were found in stomata and on cut edges following
      chlorine treatment. E. coli O157:H7 did not preferentially adhere to biofilm
      produced by Pseudomonas fluorescens on the leaf surface. In contrast to E. coli
      O157:H7, Pseudomonas adhered to and grew mainly on the intact leaf surface rather
      than on the cut edges.

PMID- 9921821
TI  - Influence of various commercial packaging conditions on survival of Escherichia
      coli O157:H7 to irradiation by electron beam versus gamma rays.
AB  - Irradiation of ground beef patties inoculated with the organism Escherichia coli
      O157:H7 was performed either by gamma rays from a cobalt 60 source or by electron
      beam generated by a linear accelerator. Patties were packaged in one of the
      following materials: nylon/polyethylene bags, Saran/polyester/polyethylene bags
      (PM2), or Saran overwrap with a Styrofoam tray inside. Bags were sealed in air or
      under vacuum and were irradiated at either 5 or -15 degrees C. Average D10 values
      (dose required to inactivate 90% of a microbial population) ranged from 0.27 to
      0.63 kGy, depending on the conditions. Overall, higher D10 values (P<0.0001) were
      obtained upon irradiation at -15 degrees C as compared with 5 degrees C. Cells
      inoculated in samples packaged in PM2 had the highest D10 values, but only if
      irradiated by electron beam at -15 degrees C (P<0.001). Since PM2 had the lowest
      oxygen permeability rate and since the temperature was too low for radicals to
      migrate easily, these conditions may have minimized the effect of oxygen- and
      water-derived radicals on microbial survival. Irradiation by gamma rays resulted
      in higher D10 values (P<0.047) than irradiation by electron beam, with the
      highest values being observed at -15 degrees C. Differences may be attributed to
      dose rate (1.0 kGy/h for gamma, 17 kGy/min for electron beam) since it is
      possible that, at low dose rates, microbial enzymes may have more time to repair
      damage to the cell due to irradiation, resulting in higher D10 values.

PMID- 9921822
TI  - Relative effectiveness of selenite cystine broth, tetrathionate broth, and
      Rappaport-Vassiliadis medium for the recovery of Salmonella spp. from foods with
      a low microbial load.
AB  - The relative effectiveness of Rappaport-Vassiliadis (RV) medium, selenite cystine
      (SC) broth, and tetrathionate (TT) broth for the recovery of Salmonella spp. from
      foods with a low microbial load was determined. RV medium made from its
      individual ingredients and incubated at 42 degrees C was compared with a
      commercial preparation of SC broth, incubated at 35 degrees C, and TT broth
      incubated at 35 and 43 degrees C, for the recovery of Salmonella spp. Twenty-one
      artificially contaminated food types that included dairy foods, spices, and egg
      products, as well as other low-microbial-load foods, were analyzed. The foods
      were inoculated with single Salmonella serovars at target levels ranging from
      0.04 to 0.4 CFU/g. No significant differences (P< or =0.05) among the selective
      enrichment broths for the recovery of Salmonella spp. from 18 of the foods were
      observed. Significantly fewer Salmonella-positive test portions of gelatin, guar
      gum, and nonfat dry milk were recovered with RV medium than with SC broth
      incubated at 35 degrees C and TT broth incubated at 35 and 43 degrees C. TT broth
      incubated at 35 degrees C recovered the greatest number of Salmonella-positive
      test portions. For the recovery of Salmonella spp. from foods with a low
      microbial load, it is recommended that TT broth incubated at 35 degrees C and RV
      medium incubated at 42 degrees C be used.

PMID- 9921823
TI  - Prevalence of Salmonella spp. and Yersinia enterocolitica in finishing swine at
      Canadian abattoirs.
AB  - The prevalence of Salmonella spp. and Yersinia enterocolitica in finishing swine
      was evaluated using samples of cecal material. Samples were taken at six
      different slaughterhouses from 1420 healthy, 5-month-old pigs, raised by 223
      producers in Quebec (1009 samples), Ontario (283), and Manitoba, Canada (128).
      Two different broth media (Rappaport-Vassiliadis and Tetrathionate brilliant
      green) were used for the selective enrichment of Salmonella spp. The recovery of
      Y. enterocolitica was done by a cold enrichment technique, followed by plating on
      a selective media (cefsulodin-irgasan-novobiocin agar). Prevalence (with a 95%
      confidence interval) of Salmonella spp. and Y. enterocolitica were, respectively,
      5.2% (4.0 to 6.4%) and 20.9% (18.8 to 23.0%). Overall, 24.6% of the animals
      tested were positive for one or both of these pathogens. Since only a few herds
      (2.8%) appeared to be highly contaminated by Salmonella spp., efforts should be
      undertaken in priority to control this pathogen in those herds.

PMID- 9921824
TI  - Cheesecake: a potential vehicle for salmonellosis?
AB  - This study was conducted to investigate the potential hazard of Salmonella
      Enteritidis surviving during the preparation and baking of cheesecake. Batters
      prepared with standard- and reduced-fat ingredients were inoculated with a 5
      strain cocktail of S. Enteritidis (10 and 10(6) CFU/g) and were then baked
      according to a typical cheesecake recipe. After baking, the cheesecakes were
      refrigerated overnight before the survival of S. Enteritidis was determined
      either by direct plating or after enrichment. Samples (approximately 25 g each)
      were aseptically cut from the center, mid (6.35 cm from edge), and side (2.54 cm
      from edge) area of each cake for microbiological analysis. Proximate compositions
      (fat, moisture, protein, ash, pH, and water activity) of both raw batter and
      final baked cheesecakes were also determined. S. Enteritidis was able to survive
      baking of cheesecake when batter was inoculated with a high population (10(6)
      CFU/g) of S. Enteritidis regardless of whether standard-or reduced-fat
      ingredients were used. Three of nine standard- and four of nine reduced-fat
      cheesecake samples contained viable S. Enteritidis. In addition, one sample
      contained viable S. Enteritidis population detectable by direct plating
      (approximately 10 CFU per g of cake). This sample was taken from the center of a
      standard-fat cheesecake that was inoculated with a high population (10(6) CFU/g)
      of S. Enteritidis. Results of this study suggest that cheesecake prepared with
      eggs of low microbiological quality or cheesecake improperly handled or stored
      could serve as a vehicle for salmonellosis.

PMID- 9921825
TI  - Prevalence and characteristics of Aeromonas species isolated from processed
      channel catfish.
AB  - From August 1994 to May 1995, 238 channel catfish fillets collected from three
      processing plants in the Mississippi Delta at four time periods were tested for
      the presence of Aeromonas species. Identification of Aeromonas spp. was
      accomplished using an automated Vitek bioassay system with gram-negative and
      nonfermenter cards. Approximately 36.1% were positive for A. hydrophila, 35.7%
      for A. sobria, and 10.9% for A. caviae. All three Aeromonas spp. were found in
      all three processing plants, and the incidence of A. hydrophila contamination
      appeared to be higher in summer than other seasons. Eighty-six percent of the
      Aeromonas isolates were hemolytic on 5% sheep blood agar plates. Most isolates
      were susceptible to chloramphenicol, neomycin, streptomycin, and trimethoprim
      sulfamethoxazole and resistant to ampicillin and bacitracin. Results suggest that
      Aeromonas spp. are prevalent in processed channel catfish, and most isolates are
      hemolytic and resistant to ampicillin and bacitracin.

PMID- 9921826
TI  - Quantitative PCR for Listeria monocytogenes with colorimetric detection.
AB  - An enzyme-linked immunosorbent assay (ELISA)-mediated polymerase chain reaction
      (PCR) technique was developed to detect and quantify Listeria monocytogenes in
      food products. The bacterial DNA was extracted from artificially contaminated
      food and co-amplified with a synthetic internal standard (IS) using primers
      specific for the target gene coding for the invasive-associated protein (i.a.p.),
      a virulence factor of L. monocytogenes (i.a.p.) or IS in the presence of
      fluorescein-dUTP PCR products were hybridized with biotinylated probes designed
      for the i.a.p. or IS, and then the hybrids were bound to a streptavidin-coated
      ELISA plate. An alkaline phosphatase-conjugated antibody to fluorescein was added
      to the plate and in the presence of substrate, PCR products were quantitated
      based on an optical density reading. The detection limit for L. monocytogenes
      experimentally inoculated into milk samples and channel catfish fillets was 20
      CFU/ml and 1-2 CFU/g, respectively. Little or no cross reaction was detected in
      the presence of other spoilage and pathogenic organisms such as Pseudomonas
      aeruginosa, Aeromonas hydrophila, Escherichia coli, and Staphylococcus aureus.
      The ELISA-mediated PCR technique, when compared to traditional methods, is more
      rapid (2 working days) for detecting and quantifying L. monocytogenes.

PMID- 9921827
TI  - High-pressure destruction kinetics of Listeria monocytogenes on pork.
AB  - Packaged fresh pork chops (30-g samples) containing an indigenous bacterial
      population of approximately 10(7) CFU/g were inoculated with 10(7) CFU of
      Listeria monocytogenes Scott A per g, heat sealed, and subjected to high-pressure
      processing at 200 to 400 MPa for up to 90 min. Total counts and the number of
      surviving L. monocytogenes cells were determined by a spread plate technique on
      tryptic soy agar and modified Oxford medium, respectively. The pressure
      destruction was characterized by a dual-behavior, consisting of a step change in
      the number of survivors (Pk0) with the application of a pressure pulse and a
      first-order rate drop in the number of survivors during the pressure hold period.
      Higher pressures resulted in higher rates of microbial inactivation, as indicated
      by their associated lower D values (and higher k values). The pressure
      sensitivities of the kinetic parameters were evaluated on the basis of Arrhenius
      and pressure death time (PDT)-type models. The results suggested that L.
      monocytogenes was more resistant to pressure inactivation than the indigenous
      microflora (the volume change of activation, deltaV* [Arrhenius model]), and Zp
      values (PDT model) were -4.17 x 10(-5) m3 mole(-1) and 134 MPa for indigenous
      microflora and -3.43 x 10(-5) m3 mole(-1) and 163 MPa for L. monocytogenes
      respectively.

PMID- 9921829
TI  - Extension of shelf life of whole and peeled shrimp with organic acid salts and
      bifidobacteria.
AB  - Microbiological and sensory characteristics of treated whole and peeled shrimp
      from the east coast of Saudi Arabia were evaluated. Shrimp samples were treated
      with organic acid salts with or without Bifidobacterium breve culture and stored
      in ice. Peeling alone extended the microbiological shelf life by 4 days.
      Treatment of whole shrimp with sodium acetate alone or potassium sorbate with
      bifidobacteria prolonged the microbiological shelf life by 3 days and increased
      the microbial generation time from 12.8 h (control) to 30.1 h or 31.4 h,
      respectively. The microbiological and sensory shelf life of peeled shrimp treated
      with sodium acetate was more than 17 days. Sodium acetate extended the microbial
      lag phase and lengthened the generation time (38.7 h compared to 15.8 h for the
      control). Micrococci and coryneforms were the predominant microorganisms in whole
      shrimp during storage. Treatment with sodium acetate maintained better sensory
      characteristics for peeled shrimp than potassium sorbate combined with
      bifidobacteria.

PMID- 9921830
TI  - Effect of shift in growth temperature on tolerance of psychrotrophic and
      mesophilic strains of Bacillus cereus to heat and sodium chloride.
AB  - A shift in growth temperature of a psychrotrophic (F3802A/84) strain and a
      mesophilic strain (B4ac-1) of Bacillus cereus grown at 30 degrees C for 10 h,
      then at 37 degrees C or 40 degrees C for 14 h, enhanced thermotolerance. Sodium
      chloride, at concentrations of 2.0 and 4.0% in brain heart infusion (BHI) broth,
      had no effect on thermotolerance of strain B4ac-1 heated at 50 degrees C, whereas
      the same concentrations of NaCl caused a decrease in thermotolerance of strain
      F3802A/84 heated at 48 degrees C. A downshift in growth temperature from 30
      degrees C to 10 degrees C followed by incubation for 3 to 9 days increased
      thermotolerance of strain F3802A/84 but not strain B4ac-1 heated in BHI broth
      containing 2.0 or 4.0% NaCl compared to thermotolerance in BHI broth containing
      0.5% NaCl. Protein analysis using one-dimensional gel electrophoresis revealed an
      increase in proteins with molecular weights of 54, 50, 44, and 42 kDa in cells of
      strain F3802A/84 and 83 and 69 kDa in cells of strain B4ac-1 subjected to an
      upshift in growth temperature from 30 degrees C to 37 degrees C or 40 degrees C,
      respectively. A downshift in growth temperature from 30 degrees C to 10 degrees C
      resulted in substantial amounts of proteins with molecular weights of 63, 40, and
      29 kDa produced by strain F3802A/84 and 63 kDa to be produced by strain B4ac-1.
      Proteins produced in response to upshift or downshift in growth temperature are
      suspected to play an important role in heat resistance of the psychrotrophic and
      mesophilic strains of B. cereus examined in this study. Changes in resistance to
      heat or refrigeration temperatures, as well as tolerance to NaCl, as affected by
      previous exposure of cells to temperature shifts may influence the ability of B.
      cereus to grow in minimally processed foods during distribution and storage.

PMID- 9921828
TI  - Combined effect of nisin and moderate heat on destruction of Listeria
      monocytogenes in cold-pack lobster meat.
AB  - The combined effect of nisin and moderate heat to increase the killing of
      Listeria monocytogenes in cans of "cold-pack" lobster was investigated. Adding
      nisin at a level of 25 mg/kg of can contents to the brine surrounding the
      lobster, in combination with a heat process giving internal can temperatures of
      60 degrees C for 5 min and 65 degrees C for 2 min, resulted in decimal reductions
      of inoculated L. monocytogenes of 3 to 5 logs, whereas heat or nisin alone
      resulted in decimal reductions of 1 to 3 logs. Such a reduced heat process to
      that currently commercially used (65.5 degrees C for 13 to 18 min, depending on
      the can size) results in significant reduction in drained weight loss, thus
      allowing considerable cost savings to the lobster-processing industry.

PMID- 9921831
TI  - Flow-through membrane-based enzyme immunoassay for rapid detection of ochratoxin
      A in wheat.
AB  - A flow-through membrane-based enzyme immunoassay for the rapid detection of
      ochratoxin A in wheat was developed (patent pending). An Immunodyne ABC membrane
      was coated with rabbit anti-mouse immunoglobulins and free protein binding sites
      were blocked. After these antibody-coated membranes were placed on an absorbent
      layer in a plastic test device, a sequential competitive enzyme immunoassay was
      performed. The following reactants were successively dropped onto the membrane:
      wash solution, a dilution of monoclonal anti-ochratoxin A immunoglobulins, wash
      solution, ochratoxin A standard solution or sample extract solution, a dilution
      of ochratoxin A-horseradish peroxidase conjugate, and wash solution. Finally,
      substrate solution (H2O2-3,3',5,5'-tetramethylbenzidine) was added for color
      reaction. The dot color intensity on the membrane was visually compared with that
      of the negative control, which showed the most intense blue color because of the
      inverse relationship between toxin concentration and color development. A
      portable colorimeter was used to confirm and quantify the visual observations. An
      ochratoxin A concentration of 0.4 ng/ml in buffer solution suppressed the color
      development completely. With the use of a simple sample preparation procedure it
      was possible to eliminate matrix interference. A wheat sample spiked with 4
      microg/kg resulted in a complete color suppression. With coated membranes, the
      immunoassay could be performed in less than 15 min.

PMID- 9921832
TI  - RpoS function in Salmonella Typhimurium LT2 monitored in a skim milk model food.
AB  - In Salmonella Typhimurium, the stationary phase sigma factor RpoS regulates the
      expression of genes associated with adaptation, survival, and virulence.
      Expression of rpoS is known to be under environmental control and yet, to date,
      there have been no studies that assess the expression of this global regulator in
      real food systems. Skim milk represents a useful model food; using an
      spvRA::luxCDABE reporter construct, we have determined RpoS availability from an
      inoculum of Salmonella Typhimurium LT2. We report that RpoS activity increases
      exponentially at the end of the logarithmic phase of growth, consistent with data
      from nutrient media.

PMID- 9921833
TI  - Eggshell membrane structure and penetration by Salmonella typhimurium.
AB  - Eggshell membrane was removed from 10 broiler hatching eggs at approximately
      monthly intervals through the productive life of a commercial flock. A piece of
      membrane (2 by 2 cm) was used to cover an opening in an apparatus designed to
      test penetration by Salmonella Typhimurium. The membrane was placed between two
      chambers as the only means of liquid transfer. The chamber above the membrane was
      filled with a suspension of Salmonella Typhimurium cells. Sampling of the bottom
      chamber provided cultural evidence of the penetration by a marker strain of
      Salmonella Typhimurium. Samples were drawn at 15 min and at 1, 3, 5, 7, 12, 24,
      and 48 h. Following the cultural penetration experiment, the same pieces of
      membrane were removed and stained for microscopic examination. Membrane structure
      was examined with the use of a confocal laser scanning microscope. Each image
      consisted of a composite of eight 1-microm optical slices showing the fibers
      making up the outer surface of the membrane. These images were transferred to an
      image analysis software package that allowed the measurement of the interfiber
      area. No clear correlation could be made between the average size of all
      interfiber areas or the total interfiber area measured in the outer 8 microm of
      the outer membrane and the ability of Salmonella Typhimurium to penetrate the
      same piece of eggshell membrane.

PMID- 9921834
TI  - Use of modified Lactobacillus selective medium and Bifidobacterium iodoacetate
      medium for differential enumeration of Lactobacillus acidophilus and
      Bifidobacterium spp. in powdered nutritional products.
AB  - Modified Lactobacillus selective agar (APT agar + sodium acetate and glacial
      acetic acid; mLBS) was compared to selective modified Lactobacillus selective
      medium (LBS agar + tomato juice and acetic acid; mLSM) and nonselective de Man
      Rogosa Sharpe (MRS) agar for the enumeration of Lactobacillus acidophilus in
      probiotic-containing powdered nutritional products. The mLBS agar was equivalent
      to MRS agar and superior to the mLSM agar for enumerating L. acidophilus in
      products stored in sealed cans at 22 degrees C. When samples were analyzed for L.
      acidophilus concentration after high temperature storage in sealed cans or
      storage in open cans at high relative humidity, the mLBS and MRS agars were
      highly correlated (r2 = 0.93). Modified Bifidobacterium iodoacetate medium (12.5
      mg iodoacetic acid/liter; mBIM) was compared to MRS agar + bile, cysteine, and
      dicloxacillin (MRS + BCD) for enumerating Bifidobacterium infantis or
      Bifidobacterium lactis in the nutritional products. The two media were equivalent
      for enumerating B. infantis in product stored at 22 degrees C in sealed cans.
      However, the two media were poorly correlated (r2<0.50) for enumeration of B.
      infantis and B. lactis in products stored in sealed cans at high temperature or
      in open cans at high relative humidity. The mLBS medium has potential industry
      application as a relatively inexpensive, convenient differential enumeration
      method for L. acidophilus. The mBIM medium cannot be recommended as a sole medium
      for enumeration of probiotic Bifidobacterium spp. in powdered nutritional
      products stored under high temperature and/or high relative humidity conditions.

PMID- 9921835
TI  - Residual alkaline phosphatase activity in pasteurized milk heated at various
      temperatures--measurement with the fluorophos and Scharer rapid phosphatase
      tests.
AB  - Milk containing three levels of milkfat (skim [0.5%], lowfat [2.0%], and whole
      [3.25%]) were heat treated at five different temperatures (59, 61, 63, 65, and 67
      degrees C) using a laboratory scale, batch pasteurization method. Heated milk
      samples were removed at 5-min intervals, immediately cooled, and then assayed
      using the quantitative fluorometric method and the qualitative Scharer rapid
      test. Mean alkaline phosphatase (ALP) activity values as measured with the
      Fluorophos method decreased in all milk preparations as the time of sampling and
      temperature of heating increased. Samples representing the three fat levels and
      heat treated at 63 degrees C for 30 min, the minimum time/temperature allowed by
      the 1995 pasteurized milk ordinance (PMO), had ALP activity values <100 mU/liter.
      All values were below the 350 mU/liter standard for fluid milk products
      established by the Food and Drug Administration and cited in the 1995 PMO.
      Evaluation of the milks for adequacy of pasteurization with the Scharer rapid
      method indicated that those same milks were adequately pasteurized.

PMID- 9921836
TI  - Effect of chemical cleaning agents and commercial sanitizers on ATP
      bioluminescence measurements.
AB  - Nine chemical cleaning agents at three concentrations were studied to determine
      the effect on ATP bioluminescence measurements from pure ATP (PATP) and ATP from
      chicken exudate (CJATP). The nine commercial cleaning and sanitizing chemicals
      were concentrated foaming acid (FA), acid sanitizer (AS), iodine cleaner
      disinfectant (ZI), alkaline cleaner-degreaser (PC), chlorinated alkaline cleaner
      (CA), chlorinated sanitizer (CS), quaternary ammonium (QA), antibiofilm agent
      (AB), and acidic peroxygen sanitizer (HP). Effect was reported as a percent
      change from the log10 relative light unit (LRLU) measurements of the control
      groups. All cleaners and sanitizers were tested at one-tenth of the
      manufacturer's recommended level (MRL), MRL, and two times MRL. FA, PC, and CA at
      all three concentrations significantly decreased PATP and CJATP LRLU. AS
      decreased PATP and CJATP LRLU at 200 and 400 ppm quaternary ammonium. ZI
      decreased PATP LRLU at MRL or greater, while CJATP LRLU were decreased by all
      concentrations of ZI tested. CS decreased PATP LRLU in a dose-dependent manner;
      however, for CJATP, LRLU decreased slightly at the two lower concentrations but
      were not affected by 1,200 ppm CS. QA at MRL or above for PATP or at all
      concentrations for CJATP significantly increased LRLU. AB decreased LRLU at all
      concentrations tested for PATP or at MRL or greater for CJATP. HPA at MRL or
      greater for PATP or at all concentrations for CJATP significantly reduced LRLU.
      These results demonstrate that commercial sanitizers and cleansers may squelch or
      increase LRLU measurements when the chemical comes into direct contact with the
      ATP bioluminescence reagents. Hence, when using ATP bioluminescence as a means of
      determining sanitary quality of food-processing equipment, it is essential to
      consider the type and concentration of chemical cleaner or sanitizer being used
      on the equipment prior to testing.

PMID- 9921837
TI  - The electronic journal: sophisters, economists, and calculators.

PMID- 9921838
TI  - Hypoxia versus ischemia.

PMID- 9921839
TI  - Justifying neurorehabilitation: a few steps forward.

PMID- 9921840
TI  - Visual loss in Alzheimer's disease: out of sight, out of mind.

PMID- 9921841
TI  - Getting a grip on the myotonic dystrophies.

PMID- 9921842
TI  - Animal model of posthypoxic myoclonus: effects of serotonergic antagonists.
AB  - OBJECTIVE: To study specific serotonin (5-hydroxytryptamine [5-HT]) receptor
      subtype antagonists in an animal model of posthypoxic myoclonus. BACKGROUND:
      Although serotonergic system dysfunction is implicated in posthypoxic myoclonus,
      anatomic specificity and linkage to receptor subtypes are not delineated.
      METHODS: The authors performed a pharmacologic study to identify specific
      serotonin receptor subtype antagonists effective in inhibiting myoclonus in
      posthypoxic rats. Sprague-Dawley rats underwent cardiac arrest for 8 minutes and
      were resuscitated. On the day of pharmacologic testing, animals were rated every
      10 minutes at -30 minutes to time 0 (drug injection) and from +60 to +150
      minutes. Using a blinded methodology, animals were injected with normal saline,
      vehicle, or one of seven serotonin antagonists given at a dose that maintains
      serotonin receptor subtype specificity: WAY100135 (5-HT1A), methiothepin mesylate
      (5-HT1B/1D/2), mesulergine hydrochloride (5-HT2A/2B), GR 127935 (5-HT1D), SR
      46349 (5-HT2), ondansetron (5-HT3), or GR 125487 (5-HT4). Drugs that produced a
      significant decrease in myoclonus compared with the control were studied in a
      dose-response study with six doses across a range from the original dose studied
      to 10% of that dose. RESULTS: Two drugs were significantly different from
      placebo: methiothepin mesylate and mesulergine hydrochloride. GR 127935 showed a
      trend toward reducing myoclonus. Dose-response studies showed that all doses of
      methiothepin mesylate and the three highest doses of mesulergine hydrochloride
      inhibited myoclonus effectively. CONCLUSIONS: 5-HT1B, 5-HT2A/2B, and possibly 5
      HT1D receptor subtypes likely play a role in posthypoxic myoclonus. More specific
      5-HT antagonists that affect these receptor subtypes are candidates for future
      testing in this model and in Lance-Adams syndrome.

PMID- 9921843
TI  - Subjective experience and behavior in acute stroke: the Lausanne Emotion in Acute
      Stroke Study.
AB  - OBJECTIVE: To assess subjective experience in acute stroke and to correlate it
      with stroke features, acute emotional behavior, and impact on seeking of medical
      care. METHODS: The authors studied patients with acute first-ever stroke
      prospectively. During the first 4 days they rated subjective experience
      (happiness, sadness, irascibility, and fear); behavioral reactions, using a
      specifically designed scale; and mood (Hamilton anxiety and depression). Fifty
      three patients (30 men, 23 women; age, 60 +/- 19 years) completed the 3-month
      follow-up. RESULTS: Seventeen patients failed to seek medical care spontaneously.
      Sixteen patients presented behavioral reactions of overt sadness, 20 presented
      indifference, 12 presented aggressiveness, 20 presented disinhibition, and 16
      presented denial. Eight patients were anosognosic and 12 were anosodiaphoric.
      Twenty-four patients expressed happiness, 20 expressed sadness, 7 expressed
      anger, and 11 expressed fear. Ten patients with aphasia could be interviewed, but
      four required delayed questioning. Denial reactions and anosognosia were
      independent. Acute denial reactions were not dependent on the side of stroke, but
      were more frequent after deep lesions (p < 0.010). Patients with a denial
      reaction had a tendency to present less subjective experience of fear (p < 0.078)
      and a higher occurrence of delayed depression (p < 0.02). Intergroup comparison
      of all measures showed that lack of seeking care was related to reactions of
      indifference (p < 0.007), a tendency toward a less subjective experience of fear
      (p < 0.078), poor recall of the acute event (p < 0.001), decreased nosognosia (p
      < 0.001), and right-side lesions (p < 0.035). CONCLUSIONS: Patients with acute
      behavioral denial had a decreased occurrence of subjective experience of fear and
      a more frequent occurrence of delayed depression. These denial reactions were
      independent of anosognosia. A subjective experience of fear was related to
      appropriate care seeking. An impaired subjective experience of fear may
      contribute, as with anosognosia, to an increased delay in consultation. All other
      emotional reactions were dissociated from the patients' subjective experience.

PMID- 9921844
TI  - Progressive motor deficits in lacunar infarction.
AB  - OBJECTIVE: To study the clinical characteristics of the progression of motor
      deficits in lacunar stroke patients. BACKGROUND: Some patients with lacunar
      infarction have progression of their neurologic deficits, but it is not known
      which patients will progress or why they progress. METHODS: The authors evaluated
      92 consecutive patients (47 men, 45 women; age, 69.4 +/- 10.9 years [mean +/-
      SD]) with first-ever stroke due to supratentorial lacunes in the internal capsule
      or the corona radiata. By defining lacunar infarction in which motor deficits
      progressed between admission and the day after admission as progressive lacunar
      infarction, the authors compared progressive lacunar infarction with stable
      lacunar infarction. RESULTS: Of 92 patients, 25 (27%) had progression of
      deficits. Diabetes mellitus (p = 0.02) and severity of motor deficit on admission
      (p = 0.006) were related independently to progression in a logistic multiple
      regression analysis. Size of the infarct was slightly larger (1.2 +/- 0.4 cm2
      versus 0.9 +/- 0.5 cm2; p = 0.01) and functional status at discharge was worse
      (median Barthel index, 45 versus 100; p < 0.001) in patients with progressive
      infarction than in those without progression. There were no significant
      differences between the two groups regarding the site of the infarct or blood
      pressure or hematocrit levels on or after admission. CONCLUSIONS: The progression
      of motor deficits is associated with a relatively poor functional outcome.
      Diabetes mellitus and the severity of motor deficit on admission may predict
      progression of motor deficits.

PMID- 9921845
TI  - Validity of prediction of the site of ruptured intracranial aneurysms with CT.
AB  - OBJECTIVE: We studied the diagnostic power of blood distribution on CT (performed
      within 72 hours after the bleed) for the site of ruptured aneurysm in 168
      consecutive patients with subarachnoid hemorrhage with either a single aneurysm
      or no aneurysm on the four-vessel angiogram or postmortem examination. METHODS: A
      neurosurgeon and a neuroradiologist blind to the results of the angiography
      independently scored the distribution of blood on the CT and predicted the site
      of the ruptured aneurysm. RESULTS: Overall agreement among raters was 52% and
      chance-adjusted agreement (kappa) was 0.42 (weighted kappa value 0.47). A
      parenchymal cerebral hematoma was an excellent predictor for the site of a
      ruptured aneurysm but was present in only a minority of cases (15%). The next
      most valid predictor was blood distribution on CT in patients with a ruptured
      anterior cerebral artery aneurysm or anterior communicating artery aneurysm
      (sensitivity 0.79, specificity 0.96, and positive predictive value 0.79 for rater
      1; sensitivity 0.77, specificity 0.97, and positive predictive value 0.90 for
      rater 2). The validity of the predictive value of blood distribution on CT in
      patients with a ruptured aneurysm of the middle cerebral artery, internal carotid
      artery, or posterior circulation arteries was either inconsistent between raters
      or low. CONCLUSION: With the exception of the presence of a parenchymal hematoma,
      the site of the ruptured aneurysm can be predicted by CT only in ruptured
      anterior cerebral artery or anterior communicating artery aneurysms.

PMID- 9921846
TI  - Internal auditory artery infarction: clinicopathologic correlation.
AB  - OBJECTIVE: To study the pathophysiology of labyrinthine infarction. BACKGROUND:
      The syndrome of sudden onset vertigo or hearing loss is commonly attributed to
      inner ear vascular disease, yet histologic studies of isolated labyrinthine
      infarction in humans have been rare and have not included a complete examination
      of the vertebrobasilar vascular system. METHODS: Temporal bones, brainstem,
      cerebellum, and the supplying blood vessels were subjected to gross and
      microscopic postmortem examinations in a 92-year-old woman who had a sudden onset
      of vertigo and hearing loss in the right ear 7 years before death. RESULTS: There
      were prominent atherosclerotic changes at the vertebrobasilar junction, but the
      internal auditory artery and its branches were patent on both sides. Histologic
      studies showed degenerative changes in the cochlea and vestibular labyrinth on
      the right. The posterior canal ampulla and saccular macule were relatively
      preserved showing partial areas of intact sensory epithelium with underlying
      nerve fibers. The right vestibulocochlear nerve showed a fibrotic scar and
      multiple patchy areas of degeneration. These findings are most consistent with a
      transient period of reduced perfusion of the internal auditory artery.
      CONCLUSION: The partial sparing of the inferior vestibular labyrinth may indicate
      a decreased vulnerability to ischemia because of its better collateral blood
      supply.

PMID- 9921847
TI  - Sonographic monitoring of midline shift in hemispheric infarctions.
AB  - BACKGROUND AND OBJECTIVE: Transcranial color-coded sonography (TS) allows a
      noninvasive, accurate evaluation of lateral displacement of the third ventricle.
      The authors studied the prognostic value of TS monitoring of the midline shift
      (MLS) in acute hemispheric stroke. METHOD: Sixteen patients with acute middle
      cerebral artery (MCA) occlusion were investigated. On admission, the median
      modified Scandinavian Stroke Scale (mSSS) score was 6.0 (range, 5 to 8). Five
      patients died from cerebral herniation (group 1), 10 survived (group 2), and 1
      patient (Patient 16) survived after decompressive surgery. TS was performed on
      days 1 to 4 (10 +/- 3, 32 +/- 4, 57 +/- 5, and 82 +/- 5 hours after onset of
      symptoms). Distance from the TS probe to the center of the third ventricle was
      measured both from the symptomatic (A) and asymptomatic (B) sides. MLS was
      calculated using the formula MLS = (A - B)/2. RESULTS: Ten hours after stroke
      onset, MLS and mSSS scores were not significantly different between the two
      groups. At 32, 57, and 82 hours, MLS was higher in group 1 (32 hours, p = 0.001;
      57 hours, p = 0.003; 82 hours, p = 0.023) whereas there was no difference in mSSS
      score after 32 hours. All patients with an MLS < 4 mm at 32 hours survived,
      whereas patients with an MLS > 4 mm died as a result of cerebral herniation, with
      the exception of the one patient who underwent decompressive hemicraniectomy.
      CONCLUSIONS: The study of MLS at 32 hours after stroke onset in patients with
      severe MCA infarctions may identify patients who are unlikely to survive. The
      value of MLS in determining the indication of decompressive craniectomy merits
      further study.

PMID- 9921848
TI  - Inpatient rehabilitation in multiple sclerosis: do the benefits carry over into
      the community?
AB  - OBJECTIVE: To determine the duration and pattern of carry-over of benefits gained
      after a short period of multidisciplinary inpatient rehabilitation. BACKGROUND:
      Few studies have evaluated the outcome of rehabilitation after discharge. Long
      term follow-up is required to establish whether gains made during the inpatient
      stay are sustained over time and in the patient's own environment. METHODS:
      Prospective single-group longitudinal study. Fifty consecutive patients with
      progressive MS undergoing inpatient rehabilitation were followed for 12 months
      after discharge. Assessments were undertaken on admission (A), at discharge, and
      subsequently at 3-month intervals for 1 year (1Y) with a battery of measures
      addressing neurologic status, disability, handicap, quality of life, and
      emotional well-being. The time taken to return to baseline level was calculated
      using summary measures, and trends in performance levels were plotted. RESULTS:
      Twelve-month data were collected for 92% of patients. Although neurologic status
      declined (median Expanded Disability Status Scale scores: A = 6.8, 1Y = 8.0),
      improvements were maintained in disability and handicap for 6 months, emotional
      well-being for 7 months, and health-related quality of life (physical component)
      for 10 months. CONCLUSIONS: The benefits gained from rehabilitation were partly
      maintained after discharge despite worsening neurologic status. Carry-over of
      benefits, however, declined over time, reinforcing the need for continuity of
      care between the inpatient setting and the community.

PMID- 9921849
TI  - Physical rehabilitation has a positive effect on disability in multiple sclerosis
      patients.
AB  - BACKGROUND: Although physical rehabilitation is commonly administered to MS
      patients, its efficacy has not been established. OBJECTIVE: We assessed the
      efficacy of an inpatient physical rehabilitation program on impairment,
      disability, and quality of life of MS patients with a randomized, single-blind,
      controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks
      of inpatient physical rehabilitation (study treatment) or exercises performed at
      home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15
      weeks by a blinded examining physician. RESULTS: No changes in impairment
      occurred in either group, as measured by the Expanded Disability Status Scale. At
      the end of the intervention the study group improved significantly in disability,
      as assessed by the Functional Independence Measure (FIM) motor domain, compared
      with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001).
      The effect size statistic was usually large or moderate in all scale scores of
      the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group
      also improved in overall health-related quality of life profile compared with
      controls; however, the difference was significant only for the mental composite
      score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging
      impairment, physical rehabilitation resulted in an improvement in disability and
      had a positive impact on mental components of health-related quality of life
      perception at 3 and 9 weeks.

PMID- 9921850
TI  - Reliability and validity of two self-report measures of impairment and disability
      for MS. North American Research Consortium on Multiple Sclerosis Outcomes Study
      Group.
AB  - OBJECTIVE: To describe the results of a multicenter study that validated two new
      patient-reported measures of neurologic impairment and disability for use in MS
      clinical research. BACKGROUND: Self-reported data can provide a cost-effective
      means to assess patient functioning, and can be useful for screening patients who
      require additional evaluation. METHODS: Thirteen MS centers from the United
      States and Canada implemented a cross-sectional validation study of two new
      measures of neurologic function. The Symptom Inventory is a measure of neurologic
      impairment with six subscales designed to correlate with localization of brain
      lesion. The Performance Scales measure disability in eight domains of function:
      mobility, hand function, vision, fatigue, cognition, bladder/bowel, sensory, and
      spasticity. Measures given for comparison included a neurologic examination
      (Expanded Disability Status Scale, Ambulation Index, Disease Steps) as well as
      the patient-reported Health Status Questionnaire and the Quality of Well-being
      Index. Participants included 274 MS patients and 296 healthy control subjects who
      were matched to patients on age, gender, and education. RESULTS: Both the Symptom
      Inventory and the Performance Scales showed high test-retest and internal
      consistency reliability. Correlational analyses supported the construct validity
      of both measures. Discriminant function analysis reduced the Symptom Inventory to
      29 items without sacrificing reliability and increased its discriminant validity.
      The Performance Scales explained more variance in clinical outcomes and global
      quality of life than the Symptom Inventory, and there was some evidence that the
      two measures complemented each other in predicting Quality of Well-being Index
      scores. CONCLUSIONS: The Symptom Inventory and the Performance Scales are
      reliable and valid measures.

PMID- 9921851
TI  - Neuroanatomic correlates of visual agnosia in Alzheimer's disease: a
      clinicopathologic study.
AB  - OBJECTIVE: To examine the neuroanatomic correlates of visual agnosia in AD.
      METHODS: The authors performed an anterograde clinicopathologic study of 23
      patients with clinically and neuropathologically confirmed AD in a 305-bed acute
      care geriatric hospital and a 165-bed acute care psychiatric hospital. The
      presence of apperceptive visual agnosia was assessed using the Ghent's
      overlapping figure test and the Gottschaldt's hidden figure test. Associative
      visual agnosia was examined using the conceptual items of the Columbia Mental
      Maturity Test. Correlations between neurofibrillary tangle (NFT) and senile
      plaque (SP) densities and visual agnosia were studied using forward stepwise
      logistic regression. RESULTS: A statistically significant relation was found
      between NFT densities in Brodmann's areas 18, 19, and 37, and associative visual
      agnosia, whereas NFT densities in the areas studied did not correlate with the
      presence of apperceptive visual agnosia. Senile plaque counts did not correlate
      with any of the neuropsychological parameters. CONCLUSIONS: These results support
      the existence of a dichotomy between associative and apperceptive agnosia, and
      show that only the former is related to the damage of secondary and high-order
      visual association areas in AD. In addition, the results suggest that SP
      densities do not represent a valuable pathologic correlate of visual agnosia in
      this disorder.

PMID- 9921852
TI  - Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM
      pooled analyses. EURODEM Incidence Research Group and Work Groups. European
      Studies of Dementia.
AB  - OBJECTIVE: To investigate the risk of AD associated with a family history of
      dementia, female gender, low levels of education, smoking, and head trauma.
      BACKGROUND: These putative factors have been identified in cross-sectional
      studies. However, those studies are prone to bias due to systematic differences
      between patients and control subjects regarding survival and how risk factors are
      recalled. METHODS: The authors performed a pooled analysis of four European
      population-based prospective studies of individuals 65 years and older, with 528
      incident dementia patients and 28,768 person-years of follow-up. Patients were
      detected by screening the total cohort with brief cognitive tests, followed by a
      diagnostic assessment of those who failed the screening tests. Dementia was
      diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed.
      (revised), and AD was diagnosed according to National Institute of Neurological
      and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association criteria. Incident rates and relative risk (95% CI) express the
      association of a risk factor for dementia. RESULTS: Incident rates for dementia
      and AD were similar across studies. The incidence of AD increased with age. At 90
      years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000
      person-years. Female gender, current smoking (more strongly in men), and low
      levels of education (more strongly in women) increased the risk of AD
      significantly. A history of head trauma with unconsciousness and family history
      of dementia did not increase risk significantly. CONCLUSION: Contrary to previous
      reports, head trauma was not a risk factor for AD, and smoking did not protect
      against AD. The association of family history with the risk of AD is weaker than
      previously estimated on the basis of cross-sectional studies. Female gender may
      modify the risk of AD, whether it be via biological or behavioral factors.

PMID- 9921853
TI  - Incidence of very mild to severe dementia and Alzheimer's disease in Denmark: the
      Odense Study.
AB  - OBJECTIVE: Calculation of incidence of dementia and AD, including cases in the
      earliest phases of the diseases. BACKGROUND: Establishment of incidence estimates
      is important for the future planning of the health care system, and incidence
      studies can offer insights into risk factors. METHODS: A total of 5,237 persons
      age 65 to 84 years were randomly drawn among people living in the municipality of
      Odense, Denmark. Of this sample 3,086 persons were eligible for the incidence
      study. All participants were examined with CAMCOG, the cognitive section of The
      Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), and the
      follow-up period was 2 years. Using multiple linear regression, the CAMCOG cutoff
      score was individualized to detect even minor cognitive decline with optimal
      precision. Possibly demented persons were further examined with the remaining
      part of the CAMDEX and neuropsychological tests. AD was diagnosed according to
      National Institute of Neurological and Communicative Disorders and Stroke
      Alzheimer's Disease and Related Disorders Association criteria for probable AD,
      and vascular dementia and dementia of other types were diagnosed according to
      Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised) criteria
      for dementia. Finally, the severity of dementia was determined according to the
      Clinical Dementia Rating scale. RESULTS: The incidence rate for very mild to
      severe dementia was 29.5 per 1,000 person-years and 20.9 for AD, and the rates
      were similar for men and women. CONCLUSION: Application of an individualized
      cutoff for the screening instrument resulted in detection of a substantial number
      of cases with very mild dementia, which subsequently resulted in higher incidence
      rates than those reported in most other studies.

PMID- 9921854
TI  - Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and
      Alzheimer's disease.
AB  - OBJECTIVE: To describe atrophic changes of the hippocampus and entorhinal cortex
      in frontotemporal dementia (FTD) and compare them with those of AD. BACKGROUND:
      The medial temporal lobe shows atrophic changes early in the course of AD, but
      whether these changes are specific to AD or occur in other degenerative
      dementias, and to what extent, is unclear. METHODS: The authors measured the
      volumes of the left and right hippocampus and entorhinal cortex from MR images
      (1.5 T, 2-mm-thick slices) in 12 patients with FTD, 30 with AD, and 30 elderly
      control subjects. RESULTS: In FTD patients, the left and right hippocampus (16%
      and 21% tissue loss) and the entorhinal cortex (28% and 27% loss) were more
      atrophic than the control subjects. Atrophy of the hippocampus in FTD was less
      severe than in AD, but atrophy of the entorhinal cortex was equally severe.
      Greater hippocampal and entorhinal cortex atrophy was present in the most severe
      patients in both groups (as high as a 49% tissue loss). The sensitivity of the
      hippocampus and the entorhinal cortex to discriminate FTD patients from control
      subjects was low (49% and 52%, respectively; specificity set at 90%), whereas
      hippocampal volumes could better differentiate AD patients from control subjects
      (80% sensitivity). CONCLUSIONS: At variance with AD, detectable in vivo atrophy
      of the hippocampus might not be an early event in FTD. Differential patterns of
      atrophy might help in the diagnostic process of the degenerative dementias.

PMID- 9921855
TI  - Cerebral metabolite abnormalities correlate with clinical severity of HIV-1
      cognitive motor complex.
AB  - OBJECTIVE: To investigate the relation between biochemical alterations and
      disease severity in HIV-cognitive motor complex (HIV-CMC). BACKGROUND: HIV-CMC
      encompasses both the milder form (HIV-minor cognitive motor disorder [HIV-MCMD])
      and the more severe form (HIV-dementia). There is no validated marker to monitor
      disease severity noninvasively. METHODS: A total of 54 patients with HIV-CMC (20
      with HIV-MCMD, 34 with HIV-dementia) and 29 seronegative healthy volunteers were
      evaluated for cerebral metabolite abnormalities using proton (1H) MRS in the
      frontal cortex, frontal white matter, and basal ganglia. RESULTS: The three
      subject groups showed different concentrations of myoinositol (MI; p = 0.0005)
      and choline-containing compounds (CHO; p = 0.004) in the frontal white matter.
      HIV-dementia patients had metabolite changes in all three brain regions whereas
      HIV-MCMD patients had abnormalities in the frontal white matter only. HIV-CMC
      patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing
      AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in
      moderate to severe stages of dementia. Furthermore, CD4 count and CSF viral load,
      but not plasma viral load, showed significant effects on cerebral metabolite
      concentrations, which in turn showed significant effects on the HIV-dementia
      scale. CONCLUSIONS: In early stages of HIV-CMC, frontal white matter showed
      evidence of glial proliferation (with elevated MI and CHO levels) and cell
      membrane injury (with increased CHO levels), but no significant neuronal injury
      (with normal NA concentrations). HIV-MCMD and HIV-dementia patients have
      different neurochemical abnormalities. Because these biochemical alterations are
      related to clinical disease severity, they may be useful surrogate markers for
      noninvasive quantitative assessment of brain injury in patients with HIV-CMC.

PMID- 9921856
TI  - Paroxysmal dyskinesias in patients with HIV infection.
AB  - OBJECTIVE: To determine the clinical features of paroxysmal dyskinesias among HIV
      type 1 (HIV-1)-seropositive patients. BACKGROUND: Movement disorders have been
      associated with HIV infection, although the full spectrum of these disorders
      remains uncertain. METHODS: Six adult HIV-1-seropositive patients presenting with
      paroxysmal dyskinesias were identified. Each patient underwent metabolic, CSF,
      EEG, and neuroimaging studies. RESULTS: Mean age at onset was 34.5 years and five
      of six patients were AIDS defined. Dyskinesias were focal, multifocal, or
      hemidystonic in four patients and generalized in another two patients. Two of the
      six patients had paroxysmal kinesigenic dyskinesias and the remaining four
      patients had paroxysmal nonkinesigenic dyskinesias. Choreoathetosis (n = 3),
      myoclonus (n = 2), postural tremor (n = 5), and dysarthria (n = 3) were observed.
      Benzodiazepines appeared beneficial in three of six patients. Two patients with
      HIV-associated dementia and paroxysmal nonkinesigenic dyskinesia had a
      progressive course to death. Autopsy of a patient with paroxysmal nonkinesigenic
      dyskinesias revealed intense astrogliosis and loss of calbindin-positive neurons
      in the subcortical gray matter. CONCLUSIONS: Paroxysmal dyskinesias may present
      as a primary HIV-1-induced neurologic syndrome. The occurrence of paroxysmal
      dyskinesias is associated with neuronal injury and loss in the subcortical gray
      matter but the mechanism remains unknown.

PMID- 9921857
TI  - Smoking and Parkinson's disease: a dose-response relationship.
AB  - OBJECTIVE: To determine whether an inverse dose-response relationship exists
      between cigarette smoking and PD among ever-smokers and ex-smokers. METHODS:
      Smoking and alcohol consumption were analyzed in 144 PD patients and 464 control
      subjects, who were frequency matched for sex, race, and age (+/-5 years), in a
      population-based case-control study of men and women > or =50 years old in the
      Henry Ford Health System. RESULTS: With never-smokers as the reference category,
      there was an inverse association between current light smokers (>0 to 30 pack
      years) and PD patients (odds ratio [OR], 0.59; 95% CI, 0.23 to 1.53), and a
      stronger inverse association of PD with current heavy smokers (>30 pack-years;
      OR, 0.08; 95% CI, 0.01 to 0.62). When former >30-pack-year smokers were
      stratified by the interval since quitting, there was an inverse association
      between those who stopped >20 years ago and PD (OR, 0.86; 95% CI, 0.42 to 1.75),
      and a greater inverse relationship with those who stopped 1 to 20 years ago (OR,
      0.37; 95% CI, 0.19 to 0.72). Alcohol consumption had no independent, significant
      association with PD, but heavy drinking (>10 drink-years) had a greater effect
      than light-moderate drinking in reducing but not eliminating the inverse
      association between smoking and PD. CONCLUSIONS: The inverse dose-response
      relationship between PD and smoking and its cessation is unlikely to be due to
      bias or confounding, as discussed, providing indirect evidence that smoking is
      biologically protective.

PMID- 9921858
TI  - Dopamine autoreceptor function is lost in advanced Parkinson's disease.
AB  - OBJECTIVE: Regional presynaptic dopaminergic function and its regulation by
      dopamine agonists in different stages of PD can be measured by L-[11C]dopa and
      PET. In the current investigation, we studied the effects of therapeutic
      apomorphine on L-[11C]dopa uptake in patients with early and advanced PD.
      BACKGROUND: With disease progression and chronic dopamine agonist treatment,
      motor response complications supervene in a majority of PD patients. It is
      assumed that both presynaptic and postsynaptic changes in the dopaminergic system
      act to modify dopaminergic efficacy. METHODS: Patients with early and advanced
      stages of PD were included in the study. All patients were investigated twice
      with PET and L-[11C]dopa drug free and during a subsequent standardized
      therapeutic apomorphine infusion. RESULTS: Subregional analysis of the striatum
      showed differences in the effects of apomorphine infusion on the L-[11C]dopa
      influx rate in the two patient categories. In patients with early and
      uncomplicated PD, apomorphine infusion decreased the L-[11C]dopa influx rate.
      This decrease was most pronounced in the dorsal part of the putamen. In advanced
      PD patients, apomorphine did not affect the striatal L-[11C]dopa influx rate.
      CONCLUSIONS: We suggest that in mild and stable PD an upregulated presynaptic
      inhibitory feedback regulation, particularly in the dorsal putamen, acts to
      maintain congruity within the dopaminergic system in response to antiparkinsonian
      medication. However, this inhibitory feedback regulation is diminished with the
      progression of nigrostriatal degeneration and chronic dopamine agonist treatment.

PMID- 9921859
TI  - The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or
      sleep apnea.
AB  - OBJECTIVE: To assess the validity of the Epworth Sleepiness Scale score (ES) as a
      measure of sleepiness among patients suspected or confirmed to have obstructive
      sleep apnea syndrome. BACKGROUND: The ES is used with increasing frequency as a
      measure of excessive daytime sleepiness in part because several studies suggested
      that the ES correlates with mean sleep latency (MSL) on the Multiple Sleep
      Latency Test and with severity of sleep apnea among patients with that disorder.
      However, associations identified between the ES and other measures were not
      strong or consistent. METHODS: The authors used regression models and
      retrospective data from a relatively large series of 237 patients to restudy how
      ES relates to MSL, to a simple self-rating of problem sleepiness (available for
      141 patients), and to two polysomnographic measures of sleep apnea severity: the
      number of apneas or hypopneas per hour of sleep and the minimum recorded oxygen
      saturation. RESULTS: The ES had a statistically significant association with self
      rated problem sleepiness but not with MSL or measures of sleep apnea severity.
      Male gender, adjusted for potential confounding variables, had considerably more
      influence on the ES than did MSL or measures of sleep apnea severity.
      CONCLUSIONS: Our data suggest that the subjectively derived ES cannot be used as
      a surrogate for the objectively determined MSL.

PMID- 9921860
TI  - Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with
      partial seizures.
AB  - BACKGROUND: Previous studies have suggested a variety of factors that may be
      associated with the presence of hippocampal formation (HF) atrophy in patients
      with complex partial seizures (CPS), including a history of complex or prolonged
      febrile seizures (FS), age at seizure onset, and epilepsy duration. OBJECTIVE: To
      determine whether epilepsy duration is related to HF atrophy. METHODS: We
      performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal
      onset on video-EEG. None had evidence for an alien tissue lesion or extra
      hippocampal seizure onset. All had a history of secondary generalization. Brain
      structures were drawn on consecutive images and pixel points summed from
      successive pictures to calculate volumes. RESULTS: Nine patients with a history
      of complex or prolonged FS had smaller ipsilateral HF volume and
      ipsilateral/contralateral ratio than did patients without a history of FS.
      Epilepsy duration had a significant relation to ipsilateral HF volume and
      ipsilateral/contralateral ratio. In a multivariate analysis, the effect of
      duration, but not age at onset or scan, was significant. Patients with a history
      of FS did not have earlier age at epilepsy onset or longer duration. CONCLUSIONS:
      A history of FS predicted the severity of HF atrophy in our patients. Age at
      onset or study was not a significant factor. Epilepsy duration, however, did have
      a significant effect, suggesting that, after an initial insult, progressive HF
      damage may occur in patients with persistent seizures.

PMID- 9921861
TI  - Subtraction SPECT co-registered to MRI improves postictal SPECT localization of
      seizure foci.
AB  - OBJECTIVE: To determine whether the detection of focal hypoperfusion by
      subtraction SPECT co-registered to MRI (SISCOM) improves the sensitivity and
      specificity of postictal SPECT in intractable partial epilepsy. BACKGROUND:
      Postictal SPECT injections are easier to perform than are ictal injections, but
      the images are more difficult to interpret and have been reported to have lower
      sensitivity and specificity. METHODS: Thirty-five consecutive intractable partial
      epilepsy patients who had postictal SPECT studies were evaluated. The following
      sets of SPECT images were separately interpreted by three blinded reviewers and
      classified as either localizing to 1 of 16 possible sites in the brain or as
      nonlocalizing: unsubtracted postictal and interictal images for conventional side
      by-side comparison, SISCOM images of hyperperfusion, SISCOM images of
      hypoperfusion, and both sets of SISCOM hyperperfusion and hypoperfusion images
      (combined SISCOM evaluation). RESULTS: Significantly higher proportions of the
      hyperperfusion SISCOM images (65.7%), the hypoperfusion SISCOM images (74.3%),
      and the combined SISCOM evaluation (82.9%) were localizing than were the
      conventional method of side-by-side comparison of unsubtracted images (31.4%; p <
      0.0001). Concordance with the discharge diagnosis was higher for the combined
      SISCOM evaluation than it was for either the hyperperfusion or the hypoperfusion
      SISCOM images alone (both p < 0.05). For the hypoperfusion SISCOM and the
      combined SISCOM evaluations, concordance of the localization with the site of
      epilepsy surgery was associated with a greater probability of an excellent
      outcome than were nonconcordant/nonlocalizing images (both p < 0.05). CONCLUSION:
      The use of SISCOM to detect focal cerebral hypoperfusion, in addition to focal
      hyperperfusion, improves the sensitivity and specificity of postictal SPECT in
      intractable partial epilepsy.

PMID- 9921862
TI  - Posterior column ataxia with retinitis pigmentosa (AXPC1) maps to chromosome 1q31
      q32.
AB  - OBJECTIVE: To establish a genetic linkage between highly polymorphic
      microsatellite loci and the disease locus responsible for an autosomal recessive
      neurodegenerative syndrome that causes posterior column ataxia and retinitis
      pigmentosa. BACKGROUND: The authors reported previously a genetic syndrome that
      causes visual impairment, proprioceptive loss, sensory ataxia, and areflexia in
      affected individuals from a large, inbred family belonging to a sectarian
      population that has been genetically semi-isolated from mainstream society for
      several centuries. METHODS: To find the disease locus responsible for this
      condition, the authors performed a genome-wide search using genetic loci spaced
      at 10 to 20-cM intervals spanning human chromosomes (chr) 1-22. Pairwise linkage
      analysis, multipoint linkage analysis, and haplotype reconstruction were used to
      delineate the candidate region containing the disease gene. RESULTS: After
      testing 226 loci that covered the entire genome, the authors identified a maximum
      lod score of 8.94 at a recombination fraction of 0.00 for locus D1S2692.
      Additional analyses placed the disease gene, AXPC1, in an 8.3-cM interval flanked
      by markers D1S2692 and D1S414 on chr 1q31-q32. CONCLUSIONS: This study suggests
      that a single genetic mutation can cause selective degeneration of the posterior
      columns of the spinal cord and retina. Finding the gene responsible for this
      syndrome may increase our understanding of the molecular basis of diseases that
      affect sensory neurons.

PMID- 9921863
TI  - Impact of neurologic signs and symptoms on functional status in peripheral
      neuropathies.
AB  - OBJECTIVE: To determine whether the Neurologic Disability Score (NDS), the
      Neuropathic Symptom Score (NSS), and the Medical Research Council (MRC)
      "sumscore" are reliable, and to determine whether they provide information
      regarding the functional status of patients with peripheral neuropathies.
      METHODS: The authors analyzed homogeneity of the frequently used outcome measures
      in 97 patients using Cronbach's alpha coefficient and corrected item-total
      correlations. Their association with functional status (sickness impact profile
      and modified Rankin score) was analyzed univariately with Pearson's and
      Spearman's correlation coefficients, and multivariately with linear regression
      analysis. RESULTS: The NDS and MRC scales were homogeneous (range of Cronbach's
      alpha, 0.81 to 0.97) compared with the NSS scales (range, 0.20 to 0.63). The
      correlation patterns between neurologic signs and symptoms and functional status
      ranged from 0.13 to 0.65. Multivariate linear regression analyses showed that 40%
      or less of patients' functional status could be explained by the three tested
      outcome measures. CONCLUSION: The NDS and MRC are reliable measures, but these
      measures do not correlate with measures of functional status.

PMID- 9921864
TI  - Visual symptoms with dural arteriovenous malformations draining into occipital
      veins.
AB  - OBJECTIVE: To determine the cause of the visual dysfunction and effect of
      treatment on dural arteriovenous malformations (DAVMs) that secondarily involve
      the occipital lobe. BACKGROUND: DAVMs are an infrequent cause of visual
      dysfunction that should be amenable to treatment if diagnosed before permanent
      visual field loss. METHODS: The records of seven patients with cerebral visual
      disturbances associated with DAVMs were analyzed with attention to visual
      symptoms, visual field testing, and vascular anatomy. RESULTS: Sudden visual loss
      occurred in five patients, two with a hemorrhage and one with a venous infarct in
      the occipital lobe. Fortification images occurred in three patients, two of whom
      had palinopsia (one with de novo formed visual hallucinations). Homonymous
      quadrantic or hemianoptic field defects, some fluctuating, were found in six
      patients. Angiography revealed each DAVM was supplied solely by dural arteries
      and drained into occipital pial veins due to retrograde blood flow through the
      sites near or in the wall or lumen of the dural venous channels that normally
      drain the occipital lobe. Unlike DAVMs in other locations, only two patients had
      occlusion of an adjacent venous sinus. These patients, particularly the two with
      posterior fossa DAVMs remote to the occipital lobe, clearly demonstrate the
      visual and neurologic dysfunction resulting from venous hypertension. In six
      patients, intra-arterial embolization of the arterial feeders and nidus (one
      patient required additional surgery) resulted in resumption of normal occipital
      venous emptying. No further visual episodes occurred in five of these six
      patients. The visual fields normalized in three patients and improved in one with
      venous infarct but were unchanged in both patients with a hemorrhage.
      CONCLUSIONS: DAVMs that drain into occipital veins cause field loss and other
      visual disturbances because of venous hypertension in the occipital lobe, which
      can be reversed by occluding the DAVM nidus. If a venous infarct or hemorrhage
      has not caused irreversible damage, visual recovery should be complete.

PMID- 9921865
TI  - Superficial siderosis of the central nervous system: a late complication of
      cerebellar tumors.
AB  - OBJECTIVE: To describe the clinical and radiologic features of superficial
      siderosis of the CNS after treatment of a cerebellar tumor. METHODS: Clinical
      assessment and MRI in four patients with superficial siderosis were performed.
      RESULTS: Four patients with superficial siderosis had been treated for a primary
      cerebellar tumor (astrocytoma in three patients, medulloblastoma in one patient)
      during childhood. All patients were treated with surgery and three received
      radiotherapy. Slowly progressive bilateral sensorineural hearing loss, gait
      ataxia, and limb ataxia appeared 8 to 22 years after diagnosis of the cerebellar
      tumor. Other clinical features were mild cognitive impairment, dysarthria,
      nystagmus, optic neuropathy, anosmia, and upper motor neuron signs. The CSF
      contained erythrocytes and increased protein. MRI with fast spin-echo T2-weighted
      and gradient-echo T2* sequences showed a hypointense rim of iron coating the
      surface of the cerebellum and brainstem. Twenty-one other patients who had
      survived more than 5 years after treatment of a primary cerebellar tumor did not
      have symptoms or signs suggestive of superficial siderosis. CONCLUSIONS:
      Superficial siderosis is an uncommon late complication of the treatment of a
      childhood cerebellar tumor, but it is probably underrecognized. The diagnosis
      should be suspected in patients who present with slowly progressive sensorineural
      hearing loss and ataxia many years after eradication of a childhood cerebellar
      tumor.

PMID- 9921866
TI  - Severe atherosclerosis of the proximal carotid arteries and vertebro-carotid
      anastomosis.

PMID- 9921867
TI  - Linkage of proximal myotonic myopathy to chromosome 3q.
AB  - We performed genetic linkage analysis in nine German proximal myotonic myopathy
      (PROMM) families using DNA-markers D3S1541 and D3S1589 from the region of the
      recently discovered gene locus of myotonic dystrophy type 2 (DM2) on chromosome
      3q. Two-point analysis supplied an lod score of 5.9. We conclude that a gene
      causing PROMM is located on chromosome 3q. PROMM and DM2 may be allelic disorders
      or may be caused by closely linked genes.

PMID- 9921868
TI  - Normalization of creatine kinase level during arthritis in a patient with Becker
      muscular dystrophy.
AB  - A patient with Becker muscular dystrophy had transient arthritis. During the
      active illness his serum creatine kinase (CK) level normalized and serum levels
      of soluble interleukin 2 (IL-2) receptor, IL-6, IL-1 receptor antagonist, and
      soluble tumor necrosis factor receptor 2 were elevated. CK increased to his usual
      levels after arthritis remission whereas the levels of inflammatory cytokines and
      their inhibitors decreased.

PMID- 9921869
TI  - Respiratory muscle involvement in Bethlem myopathy.
AB  - We report a patient from a previously reported family with autosomal dominant
      Bethlem myopathy who demonstrated childhood onset, slowly progressive limb-girdle
      muscle weakness, contractures, and progressive respiratory compromise. Chest x
      ray, pulmonary function tests, and electrophysiologic studies suggested
      respiratory muscle involvement, thus expanding the clinical repertoire in Bethlem
      myopathy.

PMID- 9921871
TI  - Multiple sclerosis associated with uveitis in two large clinic-based series.
AB  - The authors reviewed records from consecutive patients in an MS clinic (n =
      1,098) and in a uveitis clinic (n = 1,530) to select patients with "definite MS"
      and uveitis. A total of 28 of 2,628 patients (1%) were identified: 12 from the MS
      clinic (12 of 1,098; 1.1%) and 16 from the uveitis clinic (16 of 1,530; 1%). Pars
      planitis and panuveitis were most commonly encountered. The delay between the
      onset of neurologic and ocular symptoms (mean, 9 years) emphasizes the importance
      of a sequential diagnostic search throughout the patient's course.

PMID- 9921870
TI  - The clinical spectrum of sarcoglycanopathies.
AB  - A group of 204 muscular dystrophy patients were screened for immunohistochemical
      and biochemical alpha-sarcoglycan defect and their DNA was analyzed for
      pathogenetic mutation in the four sarcoglycan genes. We identified 21 patients
      with alpha-, beta-, or gamma-sarcoglycan gene mutations. Patients with alpha
      sarcoglycan gene mutations were clinically heterogeneous and showed either a
      rapid progressive or a late-onset slow course. In the slowly evolving group, a
      residual alpha-sarcoglycan protein was present, and its level correlated with a
      milder disease course and significant later inability to stand up from the floor
      (p < 0.00005). Most patients with beta- and gamma-sarcoglycan gene mutations
      presented a severe clinical course. There is a considerably different pattern of
      muscle involvement and disease course in these disorders, compared with
      dystrophinopathies.

PMID- 9921872
TI  - Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive
      hyperphenylalaninemia.
AB  - Guanosine 5'-triphosphate cyclohydrolase I (GCH) mutants (H144P and T186K)
      associated with dominant dopa-responsive dystonia were enzymatically inactive and
      inhibited the normal enzyme, suggesting that GCH activity in a heterozygote was
      <50% of control. The M211I mutant associated with recessive hyperphenylalaninemia
      was slightly active and had no inhibitory effects, so GCH activity in a
      heterozygote would be <50% of normal; therefore hyperphenylalaninemia would be
      evident only in homozygotes.

PMID- 9921873
TI  - Square-wave jerks induced by pallidotomy in parkinsonian patients.
AB  - Square-wave jerks (SWJs) are small, inappropriate saccades that intrude on steady
      fixation by taking the eye away from the target and then returning it after
      approximately 200 msec. The pathophysiology of SWJs is unknown; they have not
      been attributed to any specific lesion. We found that unilateral pallidotomy
      substantially increased the frequency of SWJs in three patients with Parkinson's
      disease. This effect is likely due to imbalance in the fixation system caused by
      asymmetric reactivation of prefrontal cortex via ascending thalamocortical
      projections. Alternatively, disruption of nigral projections to the superior
      colliculus might be responsible.

PMID- 9921874
TI  - Relief of hemiballism from a basal ganglia arteriovenous malformation after
      radiosurgery.
AB  - A patient with a 3-year history of progressive hemiballism presented with an
      unruptured arteriovenous malformation (AVM) in the contralateral caudate nucleus
      and putamen. PET demonstrated a matched reduction of cerebral blood flow (CBF)
      and cerebral metabolic rate of oxygen (CMRO2) in the basal ganglia and adjacent
      frontal lobe. The patient underwent radiosurgery for the AVM. After a period of
      no clinical change for 6 months, the movement disorder resolved by month 7 post
      treatment. The AVM was successfully obliterated 2 years after irradiation without
      any significant change in the regional CBF or CMRO2.

PMID- 9921875
TI  - Dorsolateral infarction of the lower medulla: clinical-MRI study.
AB  - We describe a man with lateral medullary syndrome associated with a long-standing
      clumsiness of the ipsilateral upper limb. MRI showed that the clinical finding of
      ipsilateral clumsiness correlated with an extension of the infarction into the
      dorsal column nuclei but was not reflected in any involvement of the more ventral
      pyramidal tract. This deficit in movement control that appears superficially like
      a hemiparesis may result from a combination of lemniscal and spinocerebellar
      deficits.

PMID- 9921876
TI  - Herpes varicella zoster encephalitis in immunocompromised patients.
AB  - The authors describe specific MRI features that suggest the diagnosis of
      varicella zoster encephalitis. MRI initially revealed discrete, subcortical,
      nonenhancing lesions that coalesced and developed enhancement. Gray matter
      involvement was seen later. Autopsy revealed spherical lesions of demyelination
      and hemorrhagic cavitation confirmed as varicella zoster encephalitis.
      Characteristic MR features may suggest the diagnosis of varicella zoster
      encephalitis, enabling definitive diagnostic testing and early institution of
      antiviral treatment.

PMID- 9921877
TI  - Isolated angiitis of the central nervous system: lack of inflammation after long
      term treatment.
AB  - A case of isolated angiitis of the CNS was observed for 5 years. Initial response
      to cyclophosphamide was followed by relapse on therapy interruption. After
      renewed treatment, clinical stabilization was achieved despite progressive
      stenoses shown by angiography. The patient died of cyclophosphamide-induced
      myelodysplastic syndrome. Autopsy revealed lack of inflammation, vascular
      scarring, and amyloid angiopathy. We conclude that cure from isolated angiitis of
      the CNS is possible and that the risk of overtreatment should be minimized.

PMID- 9921878
TI  - Associated exploratory-motor and perceptual-sensory neglect without hemiparesis.
AB  - Four of 688 consecutive patients with right hemisphere ischemic stroke showed
      acute associated exploratory-motor and perceptual-sensory neglect without
      hemiparesis (AMSNWH). All cases had anterior cortical and posterior cortical
      infarctions in which motor strip and corticospinal pathways were spared. Acute
      AMSNWH is highly suggestive of embolic infarction in the anterior and posterior
      pial artery territories.

PMID- 9921879
TI  - Significance of interictal temporal lobe delta activity for localization of the
      primary epileptogenic region.
AB  - Because interictal temporal lobe delta activity (TLDA) has been described in 30
      to 90% of patients with temporal lobe epilepsy (TLE) but has not been
      investigated in patients with extratemporal epilepsy, we sought to determine the
      localizing significance of TLDA. We compared the presurgical interictal scalp EEG
      results of 47 consecutive patients who received extratemporal resection (40
      frontal and 7 parietal-occipital) for intractable epilepsy with 43 consecutive
      patients who received anterior temporal lobectomy. We defined lateralized TLDA as
      runs of lower than 4-Hz waveforms that were easily distinguished from the
      background rhythms and were maximal at electrodes T4, F8, and T6 or T3, F7, and
      T5. The lateralized TLDA was subcategorized as temporal intermittent rhythmic
      delta activity (TIRDA) or temporal intermittent polymorphic delta activity
      (TIPDA). A chi-square test was used to determine the association of the lobe of
      the epileptogenic zone with TIRDA and TIPDA. We found TIRDA in 12 (28%) and TIPDA
      in 8 (19%) patients in the temporal lobe group, and TIRDA in 2 (4%) and TIPDA in
      9 (19%) patients in the extratemporal group. TIRDA was strongly associated with
      TLE (p < 0.003), whereas TIPDA occurred at an equal rate in both groups. Similar
      to anterior temporal epilepsy, lateralized TIPDA is present in up to 20% of
      patients with extratemporal epilepsy. The presence of TIRDA strongly suggests TLE
      but may infrequently occur in extratemporal epilepsy. Caution should be used when
      using lateralized TLDA as a presurgical localizing finding.

PMID- 9921880
TI  - Diffusion-weighted MRI in sporadic Creutzfeldt-Jakob disease.
AB  - Diffusion-weighted MRI (DWI) was used in three patients with autopsy-proven
      sporadic Creutzfeldt-Jakob disease (CJD) to provide a rapid noninvasive way to
      make this sometimes confusing diagnosis. DWI prompted the diagnosis of CJD at an
      early stage and appears to be particularly useful for monitoring the progression
      of the disease. We suggest that patients with suspected CJD and no abnormalities
      on T2- and proton density-weighted images may have cortical involvement on DWI.

PMID- 9921881
TI  - Prevalence of daytime sleepiness in a population of drivers.

PMID- 9921882
TI  - Fluctuating penile erection related with levodopa therapy.

PMID- 9921883
TI  - Brainstem tuberculoma mimicking glioma: the role of antituberculous drugs as a
      diagnostic tool.

PMID- 9921884
TI  - Focal cortical transient preceding myoclonus during lithium and tricyclic
      antidepressant therapy.

PMID- 9921885
TI  - Intravenous immunoglobulin treatment in multiple sclerosis.

PMID- 9921886
TI  - Intravenous immunoglobulin treatment in multiple sclerosis.

PMID- 9921887
TI  - An epidemiologic study of multiple sclerosis in Northern Ireland.

PMID- 9921888
TI  - 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict
      distribution of intrathecally administered chemotherapy and outcome in patients
      with leptomeningeal metastases.

PMID- 9921889
TI  - Respiratory management in acute CNS catastrophies.

PMID- 9921890
TI  - Efficacy of donepezil in Alzheimer's disease: fact or artifact?

PMID- 9921891
TI  - Intravenous levodopa in hallucinating PD patients.

PMID- 9921892
TI  - Neuropathic shoulder arthropathy associated with syringomyelia.

PMID- 9921893
TI  - Short-segment incremental studies to localize ulnar nerve entrapment at the
      wrist.

PMID- 9921894
TI  - Subacute postictal aggressions.

PMID- 9921895
TI  - Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in
      pseudoachondroplasia and multiple epiphyseal dysplasia.
AB  - Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are common
      skeletal dysplasias with impaired enchondral ossification and premature
      degenerative joint disease. The two disorders were in the past considered to be
      distinct clinical entities; however, recent studies have proven that both
      diseases can result from mutations of the gene encoding cartilage oligomeric
      matrix protein (COMP). To characterize further COMP mutations and investigate
      phenotype-genotype relationships, we screened this gene in 15 patients with PSACH
      or MED by directly sequencing polymerase chain reaction products from genomic
      DNA. We identified ten mutations involving conserved residues among the eight
      calmodulin-like repeats of the gene product: seven were novel missense mutations
      in exons 9, 10, 11, 13 or 14, and the other three resulted from deletion of one
      of the five GAC repeats in exon 13. We have found that the GAC repeats in the 7th
      calmodulin-like repeat in exon 13 represent a hot-spot for mutation, and that
      mutations in the 7th calmodulin-like repeat produce severe PSACH phenotypes while
      mutations elsewhere in the gene exhibit mild PSACH or MED phenotypes. These
      genotype-phenotype correlations may facilitate molecular diagnosis and
      classification of PSACH and MED, and provide insight into the relationship
      between structure and function of the COMP gene product.

PMID- 9921896
TI  - Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective
      in molybdenum cofactor deficiency type A.
AB  - Molybdenum cofactor (MoCo) deficiency is a rare and devastating disease resulting
      in neonatal seizures and other neurological symptoms identical to those of
      sulphite oxidase deficiency. It is an autosomal recessive disease and no therapy
      is known. Most patients harbour MOCS1 mutations, which are found in both open
      reading frames of this unusual gene encoding the first two enzymes required in
      the MoCo biosynthesis pathway, MOCS1 A and MOCS1 B, in a single transcript. We
      describe genomic details as a prerequisite for comprehensive mutation analysis.
      In an initial cohort of 24 MoCo deficiency patients, we identified 13 different
      mutations on 34 chromosomes, with a mutation detection rate of 70%. Five
      mutations were observed in more than one patient and together accounted for two
      thirds of detected mutations. These comprise the most frequent mutation, R319Q,
      which is restricted to England, two Danish/German mutations (one missense and one
      splice site mutation), a missense mutation found in England and Germany, and a
      "Mediterranean" frameshift mutation. All patients with identified mutations are
      either homozygous or compound heterozygous for mutations in either of the two
      open reading frames corresponding to MOCS1 A and MOCS1 B, respectively. This
      observation suggests the existence of more than the two previously described
      complementation groups in MoCo biosynthesis.

PMID- 9921897
TI  - The structures of the human neuronal nicotinic acetylcholine receptor beta2- and
      alpha3-subunit genes (CHRNB2 and CHRNA3).
AB  - The alpha4-subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor
      (nAChR) subunit family has recently been identified in two families as the gene
      responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a
      rare monogenic idiopathic epilepsy. As a result of this finding, other subunits
      of the neuronal nAChR gene family are being considered as candidate genes for
      ADNFLE in families not linked to CHRNA4 and for other idiopathic epilepsies.
      Alpha4-subunits often assemble together with beta2-subunits (gene symbol CHRNB2)
      to build heteromeric nAChRs. The gene encoding another abundant AChR subunit, the
      alpha3-subunit gene (CHRNA3), is present with those encoding two other subunits,
      CHRNB4 and CHRNA5, in a gene cluster whose functional role is still unclear. Here
      we provide the information on the genomic structures of both the CHRNB2 and the
      CHRNA3 genes that is necessary for comprehensive mutational analyses, and we
      refine the genomic assignment of CHRNB2 on chromosome 1.

PMID- 9921898
TI  - FISH studies of the sperm of fathers of paternally derived cases of trisomy 21:
      no evidence for an increase in aneuploidy.
AB  - Paternal nondisjunction accounts for approximately 5% of cases of trisomy 21. To
      test the hypothesis that, in some such cases, the fathers might be predisposed to
      meiotic nondisjunction, we utilized fluorescence in situ hybridization (FISH) to
      screen for aneuploidy in sperm. We analyzed sperm samples from ten males with a
      trisomy 21 offspring of paternal origin. Among these individuals, the overall
      frequency of disomy 21 was 0.15%, comparable to estimates of disomy 21 in the
      general male population. Furthermore, none of the ten fathers of trisomy 21
      individuals had significantly elevated levels of disomic sperm. Thus, our results
      provide no evidence that the occurrence of a trisomy 21 conceptus of paternal
      origin imparts an increased risk of trisomy in subsequent pregnancies.

PMID- 9921899
TI  - Refinement of genetic localization of the Alstrom syndrome on chromosome 2p12-13
      by linkage analysis in a North African family.
AB  - Alstrom syndrome is a rare autosomal recessive disorder characterized by retinal
      pigment degeneration, neurogenic deafness, infantile obesity, hyperlipidemia, and
      non-insulin-dependent diabetes mellitus. While the disease-related gene remains
      unknown, studies of the genetic isolate of French Acadians provisionally locate
      the Alstrom syndrome on chromosome 2p12-13 within a 14.9-cM interval. To confirm
      this finding in another ethnic population and refine the candidate region we
      investigated by linkage analysis a consanguineous family of North African origin,
      in which three of seven siblings displayed all major neurological and metabolic
      features of Alstrom syndrome. Genotyping was performed on an ABI377 DNA automatic
      sequencer and LOD scores were obtained with the Fastlink program. Five markers
      previously investigated in French Acadians confirmed the involvement of the
      candidate region, although pairwise LOD scores were of poor significance (Zmax =
      2.9). To further confirm homogeneity and refine the candidate region, 20
      additional markers were investigated. Haplotype analysis and allele segregation
      revealed that affected children shared a single haplotype and were homozygous for
      the eight most centromeric markers (D2S291-D2S2114), over a 6.1-cM interval.
      Significative multipoint LOD scores (Zmax = 3.96) were obtained between markers
      D2S2110/145 and D2S286. Two clusters of known genes are present in this refined
      region of chromosome 2p, the most attractive candidate being the hexokinase II
      gene. However, except for several known polymorphisms, no mutations were detected
      in the coding region of this gene. In conclusion, the location of Alstrom
      syndrome on chromosome 2p12-13 is confirmed, reducing the genetic interval to 6.1
      cM.

PMID- 9921900
TI  - Genomic structure of the human ezrin gene.
AB  - The ERM proteins, ezrin, radixin, and moesin, act as linkers between the plasma
      membrane and actin cytoskeleton. They are involved in a variety of cellular
      functions, such as cell adhesion, migration, and the organization of cell surface
      structures, and are highly homologous, both in protein sequence and in functional
      activity, with merlin/schwannomin, a neurofibromatosis-2-associated tumor
      suppressor protein. We report here the genomic structure and intron junction
      sequences of the human ezrin gene. Ezrin consists of 13 exons and spans
      approximately 24 kb genomic DNA. The coding parts of the exons range in size from
      12 bp to 275 bp and the introns from 182 bp to 7 kb. The genomic structures of
      ezrin and moesin are highly conserved, suggesting their recent divergence.
      Radiation hybrid mapping has refined the location of ezrin to the interval
      between D6S442 and D6S281.

PMID- 9921901
TI  - CCG repeats in cDNAs from human brain.
AB  - Expansion mutations of trinucleotide repeats and other units of unstable DNA have
      been proposed to account for at least some of the genetic susceptibility to a
      number of neuropsychiatric disorders, including bipolar affective disorder,
      schizophrenia, autism, and panic disorder. To generate additional candidate genes
      for these and other disorders, cDNA libraries from human brain were probed at
      high stringency for clones containing CCG, CGC, GCC, CGG, GCG, and GGC repeats
      (referred to collectively as CCG repeats). Some 18 cDNAs containing previously
      unpublished or uncharacterized repeats were characterized for chromosomal locus,
      repeat length polymorphism, and similarity to genes of known function. The cDNAs
      were also compared with the 37 human genes with eight or more consecutive CCG
      triplets in GenBank. The repeats were mapped to a number of loci, including 1p34,
      2p11.2, 2q30-32, 3p21, 3p22, 4q35, 6q22, 7qter, 13p13, 17q24, 18p11, 19p13.3,
      20q12, 20q13.3, and 22q12. Length polymorphism was detected in 50% of the
      repeats. The newly cloned cDNAs include a complete transcript of human neurexin
      1B, a portion of BCNG-1 (a newly described brain-specific ion channel), a
      previously unreported polymorphic repeat located in the 5' UTR region of the
      guanine nucleotide-binding protein (G-protein) beta2 subunit, and a human version
      of the mouse proline-rich protein 7. This list of cDNAs should expedite the
      search for expansion mutations associated with diseases of the central nervous
      system.

PMID- 9921902
TI  - A transcript map of an 800-kb region on human chromosome 11q13, part of the
      candidate region for SCA5 and BBS1.
AB  - The exon-amplification method was used to identify putative transcribed sequences
      from an 800-kb region that includes the genes for phospholipase Cbeta3 and PYGM
      on human chromosome 11q13. The clone contig consisted of ten cosmids, three
      bacterial artificial chromosomes, and one P1 artificial chromosome. A total of 83
      exons were generated of which 23 were derived from known genes and expressed
      sequence tags (ESTs). Five different EST cDNA clones were identified and mapped
      on the contig. One is a homolog of the human p70S6 kinase (p70s6 k) gene whose
      function involves the translational regulation of ribosomal protein synthesis and
      thereby impacts on ribosomal biogenesis. The gene for p70s6 k is expressed
      universally, including within adipose cells and retina, and it could play a role
      in Bardet-Biedl syndrome type 1, which has been mapped to 11q13.

PMID- 9921903
TI  - Characterization of mutations in patients with autoimmune polyglandular syndrome
      type 1 (APS1).
AB  - Autoimmune polyglandular syndrome type 1 (APS1), also known as autoimmune
      polyendocrinopathy candidiasis ectodermal dystrophy (APECED), is an autosomal
      recessive disorder characterized by the failure of several endocrine glands as
      well as nonendocrine organs. The autoimmune regulator (AIRE) gene responsible for
      APS1 on chromosome 21q22.3 has recently been identified. Here, we have
      characterized mutations in the AIRE gene by direct DNA sequencing in 16 unrelated
      APS1 families ascertained mainly from the USA. Our analyses identified four
      different mutations (a 13-bp deletion, a 2-bp insertion, one nonsense mutation,
      and one potential splice/donor site mutation) that are likely to be pathogenic.
      Fifty-six percent (9/16) of the patients contained at least one copy of a 13-bp
      deletion (1094-1106del) in exon 8 (seven homozygotes and two compound
      heterozygotes). A nonsense mutation (R257X) in exon 6 was also found in 31.3%
      (5/16) of the USA patients. These data are important for genetic diagnosis and
      counseling for families with autoimmune endocrine syndromes.

PMID- 9921904
TI  - A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic
      exon in an Alu-element in intron 8 of the human beta-glucuronidase gene.
AB  - We have previously sequenced the complete coding region and the promoter region
      of the beta-glucuronidase gene of a patient with mild mucopolysaccharidosis type
      VII (MPS VII) and identified a nonsense mutation in the gene inherited from her
      mother. The mutation inherited from her father was not found. Here, we have
      extended the sequence analysis of the introns to cover all putative lariat branch
      points and putative intronic enhancers, although no nucleotide changes have been
      found in these regions. Careful analysis of mRNA structure by reverse
      transcription/polymerase chain reaction (RT-PCR) and direct sequencing has
      revealed the inclusion of a new exon derived from an antisense Alu-repeat in
      intron 8 and the skipping of exon 9 in a large proportion of the mRNA of our
      patient. A 2-bp deletion creating a strong 5'-splice site has subsequently been
      identified in the paternal gene of the patient (IVS8+0.6kbdelTC). With a
      sensitive RT-PCR assay, we demonstrate that both the inclusion of the Alu
      cassette and the skipping of exon 9 are minor events in control samples and that
      mRNA with both alterations is only found in the IVS8+0.6kbdelTC carrier. The
      increased proportion of exon 9 skipping seems to be related to the premature
      termination of translation. This is the third report of a human disease mutation
      that creates a splice site and activates an antisense Alu-cassette; the question
      rises as to how these apparently strong cryptic exons are generally excluded from
      coding sequences.

PMID- 9921905
TI  - Relaxation of imprinting in Prader-Willi syndrome.
AB  - We describe two Prader-Willi syndrome (PWS) patients who exhibit maternal
      uniparental disomy (UPD) of chromosome 15 and unusual patterns of gene expression
      and DNA replication. Both were diagnosed during infancy as having PWS; however,
      their growth and development were atypical compared with others with this
      condition. Weight was below normal in the first patient, and height and
      development were within normal limits in the second individual. Hyperphagia and
      polyphagia were not evident in either patient. Genotypes at multiple genomic
      loci, allele-specific methylation, gene expression, and DNA replication were
      analyzed at D15S9 [ZNF127], D15S63 [PW71], SNRPN, PAR5, IPW, and D15S10 in these
      patients. The maternal imprint (based on the absence of gene expression,
      synchronous replication, and methylation of both alleles) was retained at SNRPN
      in these patients, as is the case in others with UPD. By contrast, cells from the
      first individual expressed PAR5 and ZNF127, whereas the second expressed a single
      IPW allele. Asynchronous DNA replication was observed in both patients at all
      loci, except SNRPN. These findings show that a subset of imprinted genes can be
      transcribed in some PWS patients with maternal UPD and that asynchronous DNA
      replication is coordinated with this pattern of gene expression. Relaxed
      imprinting in these patients is consistent with their milder phenotype.

PMID- 9921906
TI  - Chromosomal fragile site expression in lymphocytes from patients with
      schizophrenia.
AB  - Schizophrenia is a common complex mental disorder. The lifetime prevalence of
      this disease is about 1% across different populations. The etiology is still
      unknown despite decades of intensive study. This report is aimed at studying the
      relationship between chromosomal fragile sites and the etiology of schizophrenia.
      Lymphocytes of 72 schizophrenic patients and 66 healthy controls were cultured in
      M medium, which is deficient in folic acid, and in medium RPMI 1640 with
      distamycin A. G-banding was carried out on 100 metaphases of each individual.
      Fragile sites were characterized as specific chromosomal bands that exhibit
      nonrandom gaps or breaks. Culture in M medium resulted in significant differences
      in the total number of chromosomal lesions and the total number of cells with
      chromosomal lesions between patients and controls (P<0.001), while no difference
      was noted after exposure to distamycin A. In the case of M medium, 17 bands in
      both patients and controls were recognized as expressing fragile sites
      nonrandomly using a statistical method based on the relationship of the binomial
      and F distributions. Further analysis using Fisher's exact test revealed a
      significant excess of expression of a rare fragile site at 2q11.2 among patients
      compared with controls (P<0.05). In the case of distamycin A induction, 13 bands
      were identified as having nonrandom expression of fragile sites using the same
      statistical method. A significant excess expression of a fragile site at 9q12 was
      identified among patients compared with controls by applying Fisher's exact test
      (P<0.001). Thus, our data suggest that chromosomal bands 2q11.2 and 9q12 are
      interesting regions that may harbor important genes associated with
      schizophrenia.

PMID- 9921907
TI  - Identification of the 185delAG BRCA1 mutation in a Spanish Gypsy population.
AB  - The 185delAG BRCA1 deletion occurs with a high frequency in Ashkenazi Jews. We
      detected this mutation in two Spanish Gypsy women (the only Gypsy participants)
      in an extensive study of 90 high-risk families and 160 women with early-onset
      breast cancer. One of these Gypsy women belonged to a high-risk family and the
      other had had early-onset breast cancer. The mutation was also detected in 1 out
      of 25 Gypsy samples unrelated to breast cancer. All the samples with the mutation
      shared the marker alleles present in Jewish samples with 185delAG. This is the
      first report of this mutation in a non-Jewish well-defined ethnic population.
      According to these findings the carrier frequency of this mutation in Gypsy
      individuals could be several times higher than that of the general population,
      and this should be taken into consideration in genetic screening for cancer in
      Gypsy populations.

PMID- 9921908
TI  - Loss of heterozygosity in polycystic kidney disease with a missense mutation in
      the repeated region of PKD1.
AB  - Loss of heterozygosity (LOH) is a molecular phenomenon that denotes the loss of
      one of the two alleles at a specific locus. It is frequently associated with
      tumour suppressor genes in various cancers and also with hyperproliferative
      disorders, although not exclusively. Interestingly, in conditions where there is
      an inherited germline mutation, the lost allele is always the functional one,
      thereby rendering a phenotypically dominant disease of recessive character at the
      cellular level. A disease more recently shown to be associated with LOH is
      polycystic kidney disease type 1, a systemic disorder characterized by
      significant pleiotropy. The main pathology is from renal cyst formation that
      eventually leads to end-stage renal failure during adult life. We describe the
      identification of a missense mutation in the repeated part of the PKD1 gene, exon
      31, that substitutes valine for methionine. The mutation, M3375V, cosegregates
      with the disease phenotype in a large Cypriot family. During transplantation of
      one patient, one of the polycystic kidneys was removed and DNA was isolated from
      cystic epithelial cells. In 3 of 17 cysts examined with intragenic and flanking
      polymorphic markers on chromosome 16 we detected LOH, since the wild-type allele
      was lost, thereby rendering the affected kidneys of mosaic character. The degree
      of LOH was extensive and varied among the three cysts, supporting the
      multiplicity of expression of the phenomenon on different occasions. No LOH was
      detected for other selected loci examined. Our work further supports the
      hypothesis that the rate-limiting step in cyst formation may be the occurrence of
      a second somatic hit, although other factors may be also involved. The high
      frequency of mutations at this locus may, to a great extent, explain the
      variability in phenotype observed among patients in the same families, and the
      relatively high frequency of the disease worldwide.

PMID- 9921909
TI  - Complete mutational screening of the CFTR gene in 120 patients with pulmonary
      disease.
AB  - In order to determine the possible role of the cystic fibrosis transmembrane
      regulator (CFTR) gene in pulmonary diseases not due to cystic fibrosis, a
      complete screening of the CFTR gene was performed in 120 Italian patients with
      disseminated bronchiectasis of unknown cause (DBE), chronic bronchitis (CB),
      pulmonary emphysema (E), lung cancer (LC), sarcoidosis (S) and other forms of
      pulmonary disease. The 27 exons of the CFTR gene and their intronic flanking
      regions were analyzed by denaturing gradient gel electrophoresis and automatic
      sequencing. Mutations were detected in 11/23 DBE (P = 0.009), 7/25 E, 5/27 CB,
      5/26 LC, 5/8 S (P = 0.013), 1/4 tuberculosis, and 1/5 pneumonia patients, and in
      5/33 controls. Moreover, the IVS8-5T allele was detected in 6/25 E patients (P =
      0.038). Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L.
      These results confirm the involvement of the CFTR gene in disseminated
      bronchiectasis of unknown origin, and suggest a possible role for CFTR gene
      mutations in sarcoidosis, and for the 5T allele in pulmonary emphysema.

PMID- 9921910
TI  - Frequency of nucleated red blood cells in maternal blood during the different
      gestational ages.
AB  - We wished to determine the time of pregnancy at which optimal numbers of
      nucleated red blood cells (NRBC) are present in maternal blood. Because 30% of
      the NRBC in maternal blood are fetal, there are implications for prenatal
      screening and diagnosis. Samples of whole blood were collected from each of 225
      women at various times during pregnancy. The samples were processed by charge
      flow separation (CFS), the NRBC enumerated, and the numbers compared on a week-to
      week basis. To quantify the relationship between week of pregnancy and actual and
      log-transformed numbers of NRBC recovered, Pearson product moment and Spearman
      correlation coefficient were estimated for each of four CFS instruments and for
      the four instruments combined. When the data were analyzed, we found no
      relationship between stage of pregnancy and numbers of NRBC recovered. Even after
      logarithmic transformation, variability among the women, estimated by standard
      deviation, was large and relatively stable across the different stages of
      pregnancy. The number of NRBC recoverable by CFS appears to be constant between 7
      and 25 weeks.

PMID- 9921911
TI  - Detection of 6q deletions in breast carcinoma cell lines by fluorescence in situ
      hybridization.
AB  - Dual-color fluorescence in situ hybridization was performed to detect the
      frequency and extent of 6q deletions in ten breast carcinoma cell lines. In five
      cell lines, the 6q deletions involved large regions extending from 6q12-q16 to
      6q27, and in one the deletion extended from the region distal to YAC 751G10 at
      6q25.1 to 6q27. In two cell lines, 6q deletions occurred only in cells with
      polysomy 6, indicating that such deletions might be secondary chromosomal
      aberrations and reflect late genetic changes in breast carcinomas. In addition,
      an overrepresentation of 6q21-q22.2 was detected in one cell line.

PMID- 9921912
TI  - Mutations in the gene for the common gamma chain (gammac) in X-linked severe
      combined immunodeficiency.
AB  - X-linked severe combined immunodeficiency (XSCID) constitutes a disorder of the
      immune system caused by mutations in the gene encoding the common gamma chain
      (gammac), a subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors, which are
      necessary for lymphocyte development and function. In this study the IL2RG gene
      of 31 patients with severe combined immunodeficiency (SCID) was examined by
      nonradioactive single-strand conformation polymorphism and sequence analysis.
      Among the 11 patients with XSCID, ten different mutations were identified in the
      IL2RG gene, including eight novel mutations. Ninety percent of the mothers of the
      XSCID patients are carriers of the mutated allele. One patient showed low numbers
      of B-cells, a striking deviation from the classical B-cell-positive and T-cell
      negative phenotype.

PMID- 9921913
TI  - Mutational spectrum of the iduronate-2-sulfatase (IDS) gene in 36 unrelated
      Russian MPS II patients.
AB  - We present a mutational analysis of the iduronate-2-sulfatase (IDS) gene of 36
      Russian patients with Hunter syndrome. Among 29 mutant alleles, there were 19
      missense mutations, 1 nonsense mutation, 6 mutations affecting splice sites, and
      3 major structural alterations resulting in deletions. Of the 25 different
      mutations, 15 are novel and unique. Most of the missense mutations result in
      intermediate or severe phenotypes.

PMID- 9921914
TI  - Hematopoietic cell differentiation antigens (CD system 1997). Cancer research
      relevance.
AB  - The 6th International Workshop on Leukocyte Antigens (white cell differentiation
      antigens) continued the international cooperative effort aimed at
      characterization of all leukocyte cell surface antigens with respect to their
      biochemical properties, cell- and cell line expression, molecular and cellular
      function(s) and eventual disease relevance. Significantly, among 36 newly defined
      CD clusters identified with the aid of numerous monoclonal antibodies submitted
      to the workshop [17], 8 new clusters belonged to the endothelial section, 6 new
      CD clusters were identified within cytokine receptor section and 5 such clusters
      were characterized in the adhesion structure section, i.e. as antigens with the
      pattern of expression also on cells, tissues and cell lines outside the
      hematopoietic system (Tables 1-3). Minority of newly defined clusters appurtened
      to lineage-specific or non-lineage hematopoietic differentiation antigens (Table
      4), i.e. 5 new CD clusters within myeloid section, 3 new clusters within both non
      lineage and NK antigens, 2 T-cell antigens and one new CD cluster defined within
      both B-cell or platelet sections.

PMID- 9921915
TI  - To the incidence of nucleoli in circulating myeloblasts of patients suffering
      from acute myeloblastic, promyelocytic and myelomonocytic leukemias.
AB  - Nucleoli were studied in circulating myeloblasts of myeloblastic (FAB M1, M2),
      promyelocytic (FAB M3) and myelomonocytic (FAB M4) acute myeloid leukemias (AMLs)
      using a cytochemical procedure for the demonstration of RNA. In patients
      untreated with cytostatic chemotherapy, myeloblasts of myeloblastic acute
      leukemias possessed less frequently "active large" nucleoli and more frequently
      "inactive" micronucleoli in comparison with other investigated types of AMLs.
      When myeloblasts were classified according to the presence of functionally
      dominant nucleoli, the higher percentage of "terminal" myeloblasts containing
      only micronucleoli in this type of AML was significantly reduced in patients
      treated with the cytostatic chemotherapy. In patients suffering from
      promyelocytic leukemia treated with cytostatic chemotherapy, the decreased
      percentage of myeloblasts containing functionally dominant active large nucleoli
      was accompanied by the increased incidence of myeloblasts with functionally
      dominant "resting" ring shaped nucleoli. In myelomonocytic AML no significant
      differences were noted between patients untreated or treated with the cytostatic
      chemotherapy in the incidence of main nucleolar types in myeloblasts and
      myeloblasts classified according to the presence of functionally dominant
      nucleoli. Thus a further biological specificity might exist among leukemic blasts
      in various types of AMLs which should be considered for a rational approach to
      the therapy of these malignancies. In addition, the cytostatic chemotherapy did
      not influence incidence of the nucleolar asynchrony in myeloblasts of all
      investigated types of AML.

PMID- 9921916
TI  - Intracellular markers in acute myeloid leukemia diagnosis.
AB  - In our study we used a new proposed system of CD45 monoclonal antibody in
      combination with the side scatter (SSC) parameter as a very useful gating method
      allowing myeloblast detection especially in cases with low blasts percentage in
      examined samples. Immunological demonstration of myeloperoxidase (MPO) in the
      cytoplasm of AML blasts is considered to be a reliable and highly sensitive
      marker. Using a direct single and double immunofluorescence staining method and
      flow cytometry we evaluated the intracellular expression of two granular
      constituents of myeloid cells--MPO and lactoferrin (LF) in leukemia cells from 18
      patients at AML diagnosis, two patients in remission after allogenic bone marrow
      transplantation and in six controls. Two different fixation/permeabilization
      techniques were used: Fix&Perm, paraformaldehyde and saponin prior to monoclonal
      antibody staining in order to verify the sensitivity of two labeling methods for
      MPO. Although both reagents used in this study proved to be efficient tools for
      the fixation and permeabilization of leukemia cells, the second one was
      characterized by higher sensitivity in detection of MPO. By double staining of
      MPO and LF we were able to distinguish undifferentiated cells from the
      granulomonocytic maturation compartments in bone marrow, since LF is proposed to
      be selectively expressed from the myelocyte stage of differentiation onward.
      Cytoplasmic CD13 expression was detectable in AML blasts after their buffered
      formaldehyde-acetone fixation/permeabilization. According to our results the
      detection of MPO and CD13 markers in the cytoplasm of leukemia cells is of great
      importance in the definition of FAB M0-M1 subtype of AML. Furthermore we
      described overexpression of CD34 antigen in AML and revealed the characteristic
      marker combination when CD34 was studied simultaneously with MPO. This finding
      also coincided with some atypical phenotypic features (CD15/MPO, CD7/cCD13,
      CD2/cCD13, CD33/cCD13, MPO/cCD13) contributing to the differential diagnosis and
      allowing the immunologic monitoring of patients for the presence of residual
      disease.

PMID- 9921917
TI  - Cytogenetic study of acute myeloid leukemia: comparison of data obtained in 1991
      1996 and 1982-1988.
AB  - The results of the cytogenetic study of bone marrow cells from 110 consecutive
      patients with primary acute myeloid leukemia (AML) who were diagnosed and treated
      between 1991 and 1996 at one tertiary care institution were compared with similar
      data obtained between 1982 and 1988 in 130 patients. Despite improvements in
      cytogenetic techniques (namely FISH methods, applied in all patients with
      abnormal karyotypes since 1990) in recent years we have observed a significantly
      lower frequency of abnormal karyotypes: 52.7% versus 77.7% (p = 0.001). This was
      mainly due to the decreased frequency of patients with +8, -5, -7 and inv(16).
      The survival rate (excluding the patients who underwent a bone marrow
      transplantation) was only slightly increased.

PMID- 9921918
TI  - Pentoxifylline stimulates drug-induced apoptosis in leukemic cells.
AB  - Camptothecin (CAM) and cisplatin (cis-diamminedichloroplatinum(II), cis-Pt) were
      used as inducers of apoptosis in the mouse leukemic L1210 cells. Relatively high
      concentrations of 50 micromol cis-Pt and 50 micromol CAM, respectively, were used
      to induce the apoptotic DNA ladder. The simultaneous treatment of L1210 cells by
      the drug and pentoxifylline (PTX) resulted in a decrease of drug concentrations
      necessary for the induction of apoptosis. This study revealed that a cell cycle
      G2 checkpoint inhibitor PTX reduces time intervals necessary for the onset of
      drug-induced apoptosis in these cells. This fact might be important as the
      earlier onset of programmed cell death may decrease a risk of tumor cells to
      become resistant to drug therapy.

PMID- 9921919
TI  - Proliferating cell nuclear antigen (PCNA) expression in gestational trophoblastic
      diseases (GTD).
AB  - Gestational Trophoblastic Disease is an abnormal condition of the placenta, the
      incidence of which is very high in the state of Kerala, India. The proliferative
      rate of molar placentas in comparison with the normal placentas of comparable
      gestational age group was done in order to find out its role in the prognosis of
      this tumor by assessing the expression of PCNA in trophoblasts. PCNA expression
      was evaluated in 149 trophoblastic tumors and 96 normal placental tissue. The
      percentage of positive cells was significantly increased in molar placentas of
      the 1st trimester in comparison to the normal placentas. Correlation of the
      staining score to the regression pattern of the tumor showed a significant
      increase in the chemotherapy group when compared to the spontaneously regressing
      group. But no correlation was found between the percentage of PCNA positive cells
      with histological grade of the tumor proliferation.

PMID- 9921920
TI  - Combined therapy of B16(F10) murine melanoma using E. coli cytosine deaminase
      gene and murine interleukin-4 gene.
AB  - This paper summarizes preliminary results of combining suicide gene strategy (E.
      coli cytosine deaminase gene--CD) with immunotherapy (murine interleukin-4 gene)
      for treatment of experimental B16(F10) melanomas implanted into C57Bl/6 mice. The
      best therapeutic results, inhibition of tumor growth and prolonged survival time
      of treated vs. control mice, were obtained when plasmid expression vectors
      containing therapeutic genes were transferred into mice via DDAB/DOPE cationic
      liposome carrier on the third or fourth day following inoculation of mice with
      cancer cells. Extension of survival time has been noted in the case of two-gene
      therapy (as compared with one-gene therapy) of tumors which originated from cells
      transfected in vitro with CD gene and which were subsequently injected in vivo
      with IL-4-secreting cells. However, no improvement of therapeutic effect was
      obtained in case of mice treated with a combination of two genes transferred
      intratumorally with DDAB/DOPE cationic liposomes as compared to mice treated with
      a single gene only.

PMID- 9921921
TI  - Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in
      lung and bladder cancers.
AB  - A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST
      M1) and q (GST T1) and their implication as cancer risk factors was performed in
      a case-control study of lung and bladder cancers. Using a multiplex polymerase
      chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1
      and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder
      cancer patients, and in a community-based sample of 248 healthy, unrelated
      individuals. In both cancer groups the frequency of the GSTM1 null genotype was
      higher in comparison with that of the control group (59% and 59.7% vs. 49.6%),
      but this increase did not reach statistical significance (p > 0.05). After
      grouping by the smoking status, among smokers in both cancer groups (62.1% in
      lung cancer and 71.4% in the bladder cancer group, respectively) there were
      statistically significantly (p < 0.05) increased frequencies of the GSTM1
      deletion genotype as compared to the control group (49.6%). Smokers with absence
      of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer
      (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and
      an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2
      5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1
      effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at
      an approximately 2.5-fold higher risk of developing bladder cancer. In the lung
      cancer cases, the frequency of the putatively high risk GSTT1 null genotype was
      not increased as compared with controls. No effect of smoking was found on risk
      of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined
      analysis, the obtained results suggested that individuals who were both GSTM1
      null and GSTT1 null may be at increased risk because they lack both enzymes. The
      findings suggest that the GSTM1 null genotype may be associated with
      susceptibility to lung and urinary bladder cancer in dependence on the exposure
      to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a
      critical factor in mediating the risk of lung cancer, but may be associated with
      an increased susceptibility to bladder cancer.

PMID- 9921923
TI  - Prognostic relevance of non-Hodgkin's lymphomas cell cycle data.
AB  - Determination of proliferative activity of non-Hodgkin's lymphomas (NHL), aimed
      at improving the prediction of their clinical behavior, has gained considerable
      attention in the recent years. Flow cytometry has allowed rapid measurement of
      the cellular DNA content in terms of ploidy and proliferative activity. Flow
      cytometric DNA analysis was performed on paraffin embedded biopsy specimens taken
      from 125 patients with NHL. In 90 of them, proliferative index (PI) could be
      accurately measured and correlated with histology grade of the Working
      Formulation (WF). Intermediate and high grade NHL (54 patients) were analyzed
      together as HG-NHL. With the discrimination point for PI of 10%, the survival of
      high and low proliferative lymphomas was compared in the whole NHL group and
      within the WF prognostic groups. The median PI was 5% in LG (low grade) NHL and
      10% in HG (high grade) NHL group. Acturial survival in NHL with high
      proliferative activity (39 patients) was 31% at 5 years and 15% at 10 years, and
      in NHL with low proliferative activity (51 patients) 53% and 18%, respectively (p
      = 0.002). In HG-NHL, survival at 5 years for low proliferative cases was 55% and
      for high proliferative cases 28% (p = 0.065), whereas in the LG-NHL group it was
      54% and 28%, respectively (p = 0.059). The survival at 10 years was nearly equal
      in all groups. Proliferative index was associated with the overall survival of
      NHL in the whole group, as well as within the LG and HG prognostic categories. PI
      could differentiate more and less aggressive NHLs both within LG-NHL and HG-NHL.
      A tendency of survival curves toward continuous relapse was observed in low
      proliferative NHL and a tendency toward "plateau" in high proliferative NHL,
      irrespective of the histology grade.

PMID- 9921922
TI  - Cysteine proteases and cysteine protease inhibitors in non-small cell lung
      cancer.
AB  - In this study we investigated the levels of two lysosomal cysteine protease
      proteins cathepsin B (CB) and cathepsin L (CL) and the levels of three cysteine
      protease inhibitor proteins stefin A (SFA), stefin B (SFB) and cystatin C (CNC)
      in squamous-cell lung carcinoma (SQCLC) and matched lung parenchyma specimens and
      examined the inhibition of CB and cathepsin C (CC) activities by endogenous
      inhibitors in extracts from SQCLC, lung adenocarcinoma (LAC) and lung parenchyma
      specimens. We found that Stage I SQCLCs contained significantly increased levels
      of CB protein, CB activity and SFA protein as compared to matched lungs. Neither
      the levels of CL protein nor the levels of SFB protein nor the levels of CNC
      protein in Stage I SQCLCs and the lungs were significantly different, but the
      levels of CB and CL proteins as well as the levels of SFA and SFB proteins showed
      significant positive correlation in SQCLCs. In SQCLCs as well as in the lungs the
      level of SFB protein was significantly higher than the level of SFA protein or
      the level of CNC protein. In the lungs the levels of SFA protein and CNC protein
      revealed a weak negative correlation trend. In extracts from SQCLCs the level of
      SFA protein showed a weak negative correlation with the residual CB activity
      (i.e. the activity remaining after extract preincubation) whereas in extracts
      from the lungs the level of CNC protein displayed a weak negative correlation
      trend with the residual CB activity and with the residual CC activity. We
      observed that SQCLCs and LACs contained not only a significantly increased
      activity of CB but also a significantly higher inhibitory potential against the
      activity of endogenous CB as compared to matched lungs. Leupeptin, a small
      inhibitor of CB, was capable to protect CB in lung carcinoma and lung parenchyma
      extracts from preincubation-induced inhibition, revealing an active-site directed
      and competitive nature of CB inhibition by endogenous cystatins. Ultrafiltration
      passaged protein preparations of nominal Mr < or = 30,000 obtained from extracts
      of SQCLCs inhibited significantly higher quantities of activity of purified
      bovine spleen CC than did such protein preparations from matched lungs. Reaction
      courses of purified bovine spleen CC that had been preincubated with such protein
      preparations resembled those of endogenous CC from SQCLC and lung extracts
      showing a slow steady-state approach. These observations and the relaxation
      kinetics of CC from SQCLC and lung extracts suggest that CC in the extracts may
      be complexed with some cystatins. In conclusion, our results indicate that
      quantitatively different combinations of cystatins are the major constituents of
      the inhibitory potential against CB and CC in SQCLCs and the lungs.

PMID- 9921924
TI  - Candida parapsilosis fungemia in cancer patients--incidence, risk factors and
      outcome.
AB  - The paper presents an analysis of fungemia cases which were caused by C.
      parapsilosis in a cancer center within 10 years, with the aim to compare risk
      factors and the outcome with fungemias caused by C. albicans and other non
      albicans Candida spp. fungemias. Before 1990 (1988-1989) in our institutes C.
      parapsilosis fungemias were not observed at all. During 1990-1997, the proportion
      of C. parapsilosis among fungemias increased, in 1990-1993 from 0% to 7.1% in
      1996-1997 to 14.2-15%. It represents 25% out of non-albicans Candida spp.
      fungemias and 7.9% out of all fungemias and is the third commonest pathogen after
      C. albicans (50.5%) and C. krusei (9.9%). Two from eight (25%) C. parapsilosis
      fungemias were breakthroughs, one appeared during prophylaxis with ketoconazol
      and one with fluconazol. Considering the proportion of C. parapsilosis among
      blood cultures, 13 of 170 blood cultures contained C. parapsilosis (6.6% among
      all yeasts from blood cultures). C. parapsilosis was the second commonest fungal
      organism isolated from blood cultures (after C. albicans) in our cancer center.
      Infected vascular catheters were surprisingly not the major risk factor: central
      venous catheters were documented as a source in two cases only. The commonest
      risk factors were similar to those occurring with other fungemias--such as
      preceding antimicrobial therapy (62.5%), neutropenia (50%) and prior prophylaxis
      with azoles.

PMID- 9921925
TI  - Scoliosis circa 2000: radiologic imaging perspective. II. Treatment and follow
      up.
AB  - Plain film imaging remains important for the diagnosis and surveillance of
      scoliosis, as well as for the detection of complications after surgery. New means
      of treating scoliosis have become established and should be understood by the
      radiologist. To the well-known postoperative complications, including
      pneumothorax, pneumonia, and gastrointestinal obstruction, are added new specific
      potential problems with the new surgical methodology.

PMID- 9921926
TI  - Grading of subcutaneous soft tissue tumors by means of their relationship with
      the superficial fascia on MR imaging.
AB  - OBJECTIVE: To assess the diagnostic value of the relationship between
      subcutaneous tumors and the superficial fascia in the characterization of soft
      tissue masses. DESIGN: MR studies of 64 soft tissue masses located in the
      subcutaneous space were reviewed. We established five grades of relationship
      between tumors and superficial fascia and analyzed the probability of the lesions
      in each group being malignant. Group 1 tumors did not contact the fascia; group 2
      lesions contacted it slightly, with acute angles between the tumor and the
      fascia; group 3 lesions had wider contact with larger acute or right angles;
      group 4 tumors had even wider contact with obtuse angles with the fascia; and
      group 5 was composed of lesions that crossed the superficial fascia. RESULTS: The
      probability of a subcutaneous lesion that crosses the superficial fascia being
      malignant was 6.88 times greater than for lesions that did not cross the fascia.
      For lesions forming obtuse angles with the fascia the probability of malignancy
      was 6.3 times greater than that of tumors that did not present this sign. All
      histologically verified fascial infiltrations occurred in malignant lesions of
      groups 4 and 5. CONCLUSIONS: Malignant tumors of the subcutaneous compartment
      have a higher tendency to develop a close relationship with the fascia than
      benign lesions. Obtuse angles between superficial fascia and a subcutaneous mass
      or a lesion crossing the fascia strongly suggest malignancy.

PMID- 9921927
TI  - Computed tomography of Paget disease of the skull versus fibrous dysplasia.
AB  - OBJECTIVE: Radiologists are often challenged to review CT examinations of the
      skull without pertinent clinical information or plain radiographs. Skull lesions
      of fibrous dysplasia (FD) may often be confused with Paget disease (PD). The
      purpose of this article is to evaluate radiographic similarities and to find the
      signs that can differentiate PD from FD of the skull on head CT and to describe
      the CT imaging features of PD and FD. DESIGN AND PATIENTS: CT scans of the skull
      in eight cases of PD, 18 cases of FD (13 cases of skull and facial bones, five
      cases of only facial bones) and 10 normals were studied retrospectively. RESULTS:
      Ten features were found to be similar in PD and FD and 10 other features were
      found to be dissimilar. The frequency of the 10 differentiating features was
      evaluated to determine their reliability in distinguishing one disorder from the
      other. The differentiating features in order of significance include: (1)
      "groundglass" appearance, (2) symmetry, (3) involvement of the paranasal sinuses,
      (4) thickness of the cranial cortices, (5) involvement of the sphenoid bone, (6)
      orbital involvement, (7) nasal cavity involvement, (8) presence of a soft tissue
      mass, (9) maxillary involvement, and (10) the presence of cyst-like changes.
      CONCLUSION: These 10 signs improve the radiologist's skill in differentiating FD
      and PD.

PMID- 9921928
TI  - Langerhans' cell histiocytosis of the spine: use of MRI in guiding biopsy.
AB  - The MRI features of two cases of spinal Langerhans' cell histiocytosis with
      multilevel involvement are presented in which MRI was of help in differentiating
      active from inactive healing lesions by the demonstration of signal changes in
      the vertebral body marrow of the active lesion, manifest as low signal intensity
      on T1-weighted sequences and high signal intensity on T2-weighted sequences. This
      distinction could not be made by plain radiography or bone scintigraphy. In cases
      where biopsy is required for diagnosis, MRI is recommended to guide the biopsy
      towards levels suggestive of active involvement.

PMID- 9921929
TI  - Cartilage destruction in small joints by rheumatoid arthritis: assessment of fat
      suppressed three-dimensional gradient-echo MR pulse sequences in vitro.
AB  - PURPOSE: To assess the accuracy of different MR sequences for the detection of
      articular cartilage abnormalities in rheumatoid arthritis. DESIGN AND PATIENTS:
      Ten metacarpophalangeal joints and 10 metatarsophalangeal joints (specimens from
      arthritis patients undergoing ablative joint surgery) were examined with a fat
      suppressed (FS) 3D FLASH, a FS 3D FISP, a FS 2D fast spin-echo T2-weighted, and a
      2D FS spin-echo T1-weighted sequence. Each cartilage lesion and each cortical
      lesion was graded from 0 to 4 (modified Outerbridge staging system).
      Subsequently, the results of each sequence were compared with the macroscopic
      findings and statistically tested against each other. RESULTS: The study shows
      that 3D gradient-echo sequences with fat suppression were best for imaging and
      grading of cartilage lesions in arthritis of the small joints of the hands and
      feet. Using 3D techniques, all grade 2, grade 3, and grade 4 lesions of cartilage
      or cortical bone were detected. CONCLUSION: FS 3D gradient-echo techniques were
      best for the detection and grading of hyaline cartilage and subchondral bone
      lesions in rheumatoid arthritis. MRI has a great potential as an objective method
      of evaluating cartilage damage and bone erosions in rheumatoid arthritis.

PMID- 9921930
TI  - A comparison of bone scintigraphy and MRI in the early diagnosis of the occult
      scaphoid waist fracture.
AB  - OBJECTIVE: To determine the accuracy of MRI in the assessment of the
      radiographically occult scaphoid fracture. DESIGN: This prospective study
      compared the sensitivity and specificity of MRI for detection of radiographically
      occult scaphoid fractures with bone scintigraphy (BS), the currently accepted
      imaging modality of choice. Consecutive patients with clinical signs of a
      scaphoid injury but no evidence of fracture on plain radiographs at presentation
      and after 7-10 days were evaluated by MRI and BS. All images were reported in
      masked fashion and the sensitivities and specificities of the imaging modalities
      determined. All patients with a scaphoid fracture demonstrated by MRI or BS were
      followed for at least a year after injury. PATIENTS: Forty-three subjects (aged
      12-74 years) had both MRI and BS carried out on average 19 days from the injury
      date. RESULTS AND CONCLUSIONS: Six patients (14%) had scaphoid waist fractures.
      There were other bony injuries in a further six. In 40 patients there was
      agreement between the BS and MRI findings. In three cases there was discrepancy
      between the imaging modalities; in all three MRI was found to be the more
      sensitive and specific. MRI could become the investigation of choice for this
      injury.

PMID- 9921931
TI  - Simultaneous occurrence of a supra- and an infratentorial glioma in a patient
      with Ollier's disease: more evidence for non-mesodermal tumor predisposition in
      multiple enchondromatosis.
AB  - A case is presented in which two neuro-ectodermal tumors, an infra- and a
      supratentorial glioma, developed in a young man with multiple enchondromatosis of
      Ollier's disease. This is the third such case of multifocal low-grade glioma in
      Ollier's disease, suggesting a predisposition for non-mesodermal tumors in
      Ollier's disease. The related condition of multiple enchondromatosis and
      hemangiomas (Maffucci's syndrome) is well known for its malignant potential,
      developing both mesodermal and non-mesodermal tumors. Along with other authors,
      we support the concept of two variants of the same disease with a predisposition
      to development of tumors from various germ layers.

PMID- 9921932
TI  - Treated plasma cell lesions of bone with MRI signs of response to treatment:
      unexpected pathological findings.
AB  - Two cases of treated plasma cell lesions of bone are reported for which contrast
      enhanced MRI had suggested necrosis, based on lack of enhancement after
      gadolinium injection, and in which pathologic examinations revealed the presence
      of extensive viable neoplastic tissue. These cases highlight the need for
      cautious interpretation of contrast-enhanced MRI signs of response to treatment
      and inactivity of lesions in the setting of plasma cell neoplasms.

PMID- 9921933
TI  - Magnetic resonance imaging of elephantiasis neuromatosa.
AB  - We present the case of a 43-year-old man with neurofibromatosis type 1 who
      developed elephantiasis neuromatosa of his left leg. The gross limb enlargement
      was extremely disfiguring, and resulted in such severe disability that he was
      only able to walk a very short distance using crutches. Previous debulking
      procedures had resulted in massive blood loss, and prior to attempting further
      surgical intervention MRI studies were requested. Taking advantage of the
      excellent tissue characterisation and multiplanar imaging capabilities of MRI, we
      were able to assess the extent of soft tissue and osseous involvement. The use of
      recently developed MR angiographic sequences enabled us to non-invasively provide
      detailed images to assess the relationship of the lesions to the major vessels,
      as well as the vascular supply and angiographic features of the lesions
      themselves. This article describes our MRI-based findings, which precluded
      debulking surgery in this unusual manifestation of neurofibromatosis.

PMID- 9921934
TI  - Sclerotic lesions of the cervical spine in sarcoidosis.
AB  - Sarcoidosis is a common multisystem disorder characterized by noncaseating
      epithelial granulomata, with osseous involvement typically seen in 5% of
      patients. While the lace-like or cystic pattern frequently seen in radiographs of
      the phalanges is well appreciated, sclerotic lesions of the spine are uncommon.
      We review a case of sarcoidosis of the cervical spine with sclerotic changes that
      mimicked blastic metastatic disease.

PMID- 9921935
TI  - Radiographically ossified ganglion cyst of finger in a swimmer.
AB  - Ganglion cysts are fibrous-walled cystic lesions closely associated with joint or
      tendon sheaths and contain gelatinous mucinous fluid. The radiographic appearance
      is usually normal. Calcification or ossification in these cysts is extremely
      unusual. We report on an unusual appearing ganglion cyst of the little finger in
      a swimmer with ossification resembling myositis ossificans.

PMID- 9921936
TI  - Bilateral lunate intraosseous ganglia.
AB  - An intraosseous ganglion is a relatively uncommon, benign, cyst-like lesion that
      occurs in young and middle-aged adults. Most commonly seen adjacent to the hip,
      ankle, knee, or wrist, they are histologically identical to their soft tissue
      counterparts. A review of the literature revealed only two previously reported
      examples of bilateral symmetrical ganglia of the lunate bones.

PMID- 9921937
TI  - Molecular biology of colorectal cancer and clinical consequences for colorectal
      cancer syndromes.
AB  - Because of the accomplishments in biotechnical research in the past few decades
      our knowledge about the molecular mechanisms of carcinogenesis has grown rapidly.
      Colorectal cancer has been one of the most intensively investigated tumor
      entities, and it seems to be well established that colorectal tumor growth is
      associated with an accumulation of acquired somatic mutational events in tumor
      suppressor genes and oncogenes. Recent progress in our understanding of the
      molecular basis of the most prevalent colorectal cancer syndromes, such as
      hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous
      polyposis (FAP), is reflected by modifications in diagnosis and therapy.
      Identification and characterization of the causative genes for these colorectal
      cancer syndromes have enabled precise presymptomatic detection of mutations in
      individuals who bear an a priori risk of about 50% of developing colorectal
      cancer. Genotype-phenotype correlations might further increase the clinical
      management of hereditary colorectal cancer. Even though developments in cancer
      research are restricted to the minority of individuals with hereditary cancer
      syndromes, growing knowledge about the effect of low penetrance variations in
      tumor suppressor genes may affect the diagnosis and therapy of sporadic
      colorectal cancer.

PMID- 9921938
TI  - Sphincter preserving techniques: from anterior resection to coloanal anastomosis.
AB  - Nowadays surgery offers a complete spectrum of techniques for the treatment of
      rectal cancers. Progress in preoperative diagnostic techniques, especially in
      endoluminal ultrasound, and in the knowledge of anorectal physiology allows the
      surgeon to adopt a very individual strategy for the various tumor types. The
      situation has changed even for tumors of the middle and distal thirds of the
      rectum, which formerly were treated predominantly by abdominoperineal
      exstirpation. These can also be treated by sphincter-preserving techniques, the
      most ambitious of which is intersphincteric resection with coloanal anastomosis.
      Our experience shows that this method is not only comparable to the alternatives
      of conventional anterior resection and extirpation in terms of postoperative
      morbidity and mortality but also achieves excellent oncological results. Of
      course, anorectal function is significantly altered by this type of surgery.
      Still, after an adaptive period of about 6-12 months a very satisfactory
      functional result is reached. Further functional improvement, especially in the
      early postoperative period, can possibly be expected from reconstruction with
      creation of a colon pouch.

PMID- 9921939
TI  - Mesorectal lymph node dissection: is it beneficial?
AB  - Locoregional recurrences and distant metastases are the determinants of the long
      term prognosis following curative resection of rectal carcinoma. While distant
      metastases cannot be affected by the surgical treatment of the primary tumor,
      avoidance of local recurrence by the surgeon is of special significance as the
      predominant prognostic factor. Analysis of the long-term results achieved by
      various surgeons led to the concept of mesorectal excision - the removal of the
      rectum together with all additional tissue invested by the adjacent visceral
      fascia, that is, fatty tissue, lymph nodes, and lymphatic vessels, by sharp
      dissection of the appropriate anatomical plane. In our own patient material the 5
      year survival rate following R0 resection was 85% for all stages, provided no
      local recurrence developed. This contrasts with a figure of only 23% in those who
      did develop local recurrence. The local recurrence rate decreased from 39.4%,
      with a 50% 5-year survival rate in 1974, to 9.8% and a 71% survival rate in 1991,
      although the rate of distant metastases remained constant. Among the patients
      treated between 1988 and 1994 the local recurrence rate was determined by depth
      of infiltration (1987 UICC classification: pT1 0%, pT2 10%, pT3 14%, pT4 28%),
      extent of lymph node infiltration (pN0 6%, pN1 15%, pN2 26%, pN3 25%), grading
      (G1 9%, G2 12%, G3 21%), and location within the rectum (upper third 13%, middle
      third 8%, lower third 17%), with combinations of unfavorable initial factors
      leading to higher local recurrence rates. The elevated local recurrence rates
      seen in the 1970s, in particular in the case of tumors of the lower third, were
      traced retrospectively to incomplete mesorectal excision, the implementation of
      which reduced the local recurrence rate initially to less than 10%, and then to
      the current 4.1%. From the oncological point of view, mesorectal excision must be
      considered to confer considerable benefit. In the case of carcinomas of the upper
      third of the rectum, mesorectal resection carried out to just 5 cm below the
      lower tumor edge is sufficient, however, without coning, while deeper carcinomas
      mandate total mesorectal excision.

PMID- 9921940
TI  - Radical resection with autonomic nerve preservation and lymph node dissection
      techniques in lower rectal cancer surgery and its results: the impact of lateral
      lymph node dissection.
AB  - Lateral lymph node metastases occur in 9% of rectal cancer patients. For cancers
      localized in the lower rectum below peritoneal reflection, the frequency
      increases to 13% of all cases and to 25.5% in those of Dukes' stage C. The most
      important technique in colorectal surgery for decreasing local failure in the
      pelvis is lateral lymph node dissection. Today, however, it is also regarded as
      crucial that with perfect lymph node dissection of the lateral area outside of
      the pelvic plexus, the postoperative functions of urination and sexual ability
      are preserved. Since 1988 we have performed autonomic nerve-preserving curative
      resection (ANP) with lateral dissection in most patients with advanced lower
      rectal cancer. The mean 5-year survival rate of patients with lateral lymph node
      metastasis from the lower rectum was 37.5%, improving from 32.1% to 43.4% during
      this period. In cases of ANP with lateral dissection the local recurrence rate
      was 4.8% overall and 7.4% in the Dukes' C group. Postoperative urinary function
      has been good or fair in all ANP patients. Sexual function remained problematic,
      especially regarding male ejaculation. We describe our method for preserving the
      autonomic nervous system in the pelvis and for achieving complete dissection in
      the lateral area.

PMID- 9921941
TI  - Adjuvant radiochemotherapy--what is the patients benefit?
AB  - BACKGROUND: Local relapse is a major problem after potentially curative rectal
      cancer surgery. Although the incidence of local recurrences may be reduced by
      specialized surgical techniques such as total mesorectal excision (TME), local
      relapse rates of 20% or higher are the surgical reality today. Studies using
      adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or
      immunotherapy have tried to reduce local relapse rates and distant progression.
      Postoperative radiochemotherapy has been the recommended standard, after complete
      resection of Union Internationale Contra la Cancrum (UICC) stages II and III
      rectal cancers. In view of recent positive results with preoperative radiotherapy
      of TME without adjuvant therapy, we found it important to review the literature
      to update the recommendable adjuvant procedure in rectal cancer. METHOD/PATIENTS:
      The literature from 1985 to May 1998 was reviewed for studies trying to either
      confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled
      trials were analyzed with regard to their effectiveness in reducing the absolute
      rates of local recurrence and improving survival. RESULTS: Two trials applying
      adjuvant radiotherapy were able to demonstrate the reduction of local relapse
      rates, one trial with marginal significance, both without impact on survival.
      Four trials involving 1104 patients with rectal cancer stages UICC II-III
      compared postoperative radiochemotherapy with either surgical controls, adjuvant
      radiotherapy or conventional radiochemotherapy. In these trials, local relapse
      rates were significantly reduced by 11-18%, and survival rates significantly
      improved by 10-14%. Severe acute toxicities occurred in 50-61% of the patients,
      compromising compatibility, and caused death in 0-1%. Small-bowel obstruction
      leading to surgery was noted in 2-6% and to death in up to 2% of the patients.
      Intraoperative radiotherapy (IORT) improved local control and survival after
      surgery of locally advanced disease/local relapse. CONCLUSION: In view of four
      trials demonstrating a significant benefit of postoperative radiochemotherapy and
      with regard to recent still-debatable results of preoperative short-term
      radiotherapy optimal surgery with lowest local relapse rates plus postoperative
      radiochemotherapy remains the actual recommendable standard for rectal cancer
      surgery in R0 resected tumors stages UICC II+III.

PMID- 9921942
TI  - Quality of life research in patients with rectal cancer: traditional approaches
      versus a problem-solving oriented perspective.
AB  - The present paper critically appraises two recent overviews of the literature on
      rectal cancer and quality of life (QL). These reviews focus on the Anglo-American
      literature, largely neglect research from other countries, and provide little
      stimulus regarding future research directions. As an alternative perspective we
      propose the concept of problem-solving oriented QL research. The major theme is
      that the QL concept must be integrated into the clinical arena. To begin with, QL
      researchers must make themselves understandable. We outline several ways in which
      this can be achieved: (a) placing QL in a broader concept together with outcomes
      that are more familiar to clinicians; (b) depicting individual patients in the
      form of QL profiles; (c) clarifying the psychosocial/clinical correlates of
      particular QL scores of interest; and (d) conducting studies with a definitive
      practical goal in mind and integrating practitioners and patients into the study
      group. We illustrate the feasibility of such a research program by performance
      data from our Marburg-Biedenkopf field trial. Pursuing an ambitious research
      strategy that integrates experimental and applied research, the QL movement will
      have the chance to show that it is not merely l'art pour l'art, but indeed is
      beneficial to society.

PMID- 9921943
TI  - A new method to prevent wound infection: a controlled clinical trial in patients
      with combined liver and bile duct resection.
AB  - INTRODUCTION: Despite advances in antibiotic prophylaxis, postoperative wound
      infection remains a major source of morbidity after digestive surgery. Its
      prevention is a challenging problem, especially in high-risk patients. The
      authors introduced a new method to prevent surgical wound infections and
      evaluated its efficacy in a prospective, randomized trial in markedly high-risk
      patients. METHODS: Patients with biliary tract carcinoma who were scheduled to
      undergo combined liver and extrahepatic bile duct resection with biliary
      reconstruction were randomly assigned to one of two groups, well matched in terms
      of clinical characteristics at baseline. In one group the new treatment was
      employed (sealed group, n=31), and in the other the wound was treated in the
      usual fashion (open group, n=28). In the sealed group, povidone-iodine gel was
      administered to the subcutaneous tissue, and the skin and peritoneum were
      approximated with a continuous suture. Wound infection was registered up to 30
      days after surgery. RESULTS: Wound infection occurred in 18 patients: 5 (16%)
      patients in the sealed group and 13 (46%) in the open group (P<0.05). All 18
      underwent preoperative percutaneous transhepatic biliary drainage and had
      positive bile culture findings. In 13 of these 18 patients (72%) the
      microorganisms isolated from the infected wound were identical to those in the
      bile. CONCLUSIONS: Our results confirm the close association between infected
      bile and wound infection in hepatobiliary surgery. Our new method, "direct wound
      sealing," is simple, easy to perform, virtually cost-free, and has the potential
      to prevent wound infections even in markedly high-risk patients.

PMID- 9921944
TI  - Stromal sarcoma of the stomach--a report of 20 surgically treated patients.
AB  - BACKGROUND: Twenty patients with gastric stromal sarcomas underwent surgery at
      the University Hospital of Hamburg-Eppendorf from 1979 to 1995. Symptoms were
      nonspecific. Exact preoperative diagnosis was difficult because of submucosal
      tumor growth. Operations varied from excision of the gastric wall to extended
      gastrectomy (pancreas, spleen, partial liver resection). RESULTS: In 16 cases,
      tumor could be resected with wide margins (R0). In four cases, tumor was found at
      the resection line (R1). After a median follow-up of 69 months, 12 patients with
      R0 resections (including tumors with poor differentiation or infiltration of
      surrounding organs) lived tumor free, and two died due to other causes. All four
      patients with R1 resections died because of tumor disease within 40 months. All
      patients had a mean survival time of 59 months and a 5-year-survival rate of 69%.
      CONCLUSIONS: Our series shows that not all gastric malignancies have a dismal
      prognosis, but that gastric stromal sarcomas have a favorable follow-up if
      resected with wide margins at initial surgery.

PMID- 9921945
TI  - Spontaneous regression of hepatocellular carcinoma confirmed by surgical
      specimen: report of two cases and review of the literature.
AB  - Two cases with spontaneous regression of a histologically confirmed
      hepatocellular carcinoma (HCC) are presented. This rarely seen phenomenon of a
      spontaneous tumor involution is discussed and compared with the current
      literature. The clinical symptoms were very similar to that of a liver abscess. A
      56-year-old male suffered from a multicentric, highly differentiated, trabecular
      HCC. First symptoms were epigastric pain, septic fever and arthritis. The tumor
      marker AFP was constantly normal and no hepatitis could be verified. A resection
      of the tumor was performed. In patient 2, a 74-year-old male, a multicentric,
      clear cell HCC was found. The patient had completely recovered from hepatitis
      type B and within the liver tissue no viruses could be identified. Clinical
      symptoms were mainly characterized by upper abdominal pain and septic fever. AFP
      was excessively elevated (3850 ng/ml) but returned to normal preoperatively. In
      both cases, the specimen showed a subtotal necrotic HCC with insignificant
      amounts of vital tumor cells. Neither patient had a liver cirrhosis
      macroscopically, however patient 2 had local periportal fibrosis histologically.
      After 24 and 41 months of follow-up, respectively, both patients are in good
      health

PMID- 9921946
TI  - The clonality of nodules in recurrent goiters at second surgery.
AB  - INTRODUCTION: Some studies showed that in multinodular goiters clonal and
      polyclonal nodules coexist. The clonality of nodules in recurrent goiters is,
      however, still unknown and may contribute to help explain the pathogenesis of
      this thyroid disease. METHODS AND RESULTS: The clonality of 14 nodules derived
      from recurrent goiters was assessed by means of an X-chromosome-inactivation
      method. Of 14 nodules, 10 showed a polyclonal pattern, 3 were clonal and, in 1
      case, the result remained unclear. The mean age of the patients with recurrent
      goiter at the time of their first operation was significantly lower than the mean
      age of 50 patients who underwent thyroid surgery for the first time over the same
      period of time (34.6+/-10.9 years vs 53.7+/-13.5 years; P<0.05). The mean
      interval between first and second operation was 18 years. CONCLUSION: The finding
      that nodules in recurrent goiters are predominantly polyclonal suggests that
      these lesions have their origin in a de novo proliferation of different cohorts
      of thyrocytes due to unknown growth stimulating molecular events.

PMID- 9921947
TI  - Is there an ectopic secretion of monomeric calcitonin in the human being?
AB  - INTRODUCTION: Persistent detectable calcitonin (CT) values can be frequently
      observed after treatment of medullary thyroid carcinomas (MTCs). Apart from
      residual C cells or incomplete tumor extirpation, ectopic CT production should be
      taken into account. CT determination in patients without MTC and after total
      thyroidectomy should reveal to what extent, apart from the C cells, other
      neuroendocrine cells show a relevant CT production. OBJECTIVES: The objective of
      this study was to find out whether ectopic CT production can be detected using an
      assay specifically recognizing the monomeric form of CT. METHODS: The CT serum
      values were obtained from 94 healthy individuals and 64 patients who had
      undergone total thyroidectomy and radioiodine therapy because of follicular or
      papillary carcinoma. RESULTS: In the group of thyroidectomized patients, the CT
      values were below the detection limit of the assay. In the tested patients, there
      was neither a physiological (C cell) nor a pathological (MTC cell) secretion of
      monomeric CT. CONCLUSION: A relevant ectopic monomeric CT production could be
      excluded because the patients were without detectable CT concentration. For this
      reason, postoperative CT concentrations of the monomeric form in MTC patients can
      be traced either to remaining C cells or to tumor cells. For a differentiation of
      these two possibilities further diagnostics is necessary.

PMID- 9921949
TI  - A human carcinoma model in athymic rats reflecting solid and disseminated
      colorectal metastases.
AB  - We studied the metastatic properties of human tumor cells and tumor cell
      dissemination in a xenograft tumor model for human colorectal carcinoma in
      athymic rats which shows a reproducible pattern of metastases similar to the
      clinical situation. Such a model is also attractive for evaluating several
      therapeutic approaches. The tumor cell lines HT-29 and WiDr which are derived
      from the same colorectal tumor and exhibit a similar tumorigenic potential after
      subcutaneous injection were injected into the portal venous system of 4-week-old
      male nude rats. After injection of WiDr cells no liver metastases were observed;
      however, 50% of the rats developed liver metastases 4-12 weeks after injection of
      HT-29. Immunostaining of the liver cryosections at different times after
      injection revealed a total disappearance of WiDr cells within the first 12 h. A
      subpopulation of HT-29 (HT29-b) with increased metastatic activity was isolated
      by double selection and recultivation of cells from induced liver metastases.
      After a 6- to 12-week period rats injected with HT-29b showed a pattern of
      metastases with additional lung metastases and in some cases peritoneal
      carcinosis. In addition to immunohistochemistry cytokeratin 20 reverse
      transcriptase-polymerase chain reaction was confirmed to be a sensitive and
      specific tool for the detection of disseminated tumor cells in different
      compartments.

PMID- 9921948
TI  - Major injury induces increased production of interleukin-10 in human granulocyte
      fractions.
AB  - Patients with severe trauma or polytrauma frequently acquire alterations in
      immune functions which are correlated to dysbalanced cytokine synthesis. In these
      settings the role of polymorphonuclear neutrophil granulocytes (PMN) as cytokine
      producing cells is less well characterized. The immunosuppressive role of
      interleukin (IL)-10 is well known, and increased systemic IL-10 levels are
      related to the severity of injury and to posttraumatic complications. We
      determined concentrations of IL-10 in culture supernatants of 30 individual PMN
      fractions isolated from 18 severely traumatized patients (15 polytraumata, Injury
      Severity Score: 18-41, 3 severely burned patients) admitted to intensive care
      units. IL-10 was analyzed by ELISA (R&D Systems, Wiesbaden, Germany). PMN were
      isolated from EDTA-anticoagulated peripheral blood employing a one-step procedure
      based on a discontinuous double Ficoll gradient. The cells [1 x 10(6)/ml RPMI
      1640 supplemented with 10% fetal calf serum and 25 mM N-(2-hydroxyethyl)
      piperazine-N'-(2-ethanesulfonic acid] were stimulated with 0.05% heat-killed
      Staphylococcus aureus (Pansorbin, Calbiochem-Novabiochem, Bad Soden, Germany) for
      24 h using cell culture conditions. Our results show that PMN fractions of
      traumatized patients produce significantly (P<0.008) higher amounts of IL-10
      (354+/-95 pg/ml, n = 30) than normal healthy donor cells (125+/-95 pg/ml, n = 7).
      IL-10 release from PMN fractions exceeded the release from isolated patients'
      peripheral blood mononuclear cells induced by similar stimulation or by
      stimulation with toxic shock syndrome toxin-1 (10 ng) and concanavalin A (2
      microg). Our results provide evidence that PMN fractions play an active role in
      the development of posttraumatic immunosuppression by autocrine or paracrine
      mechanisms, for example, by suppressing one's own antimicrobial activities or
      determining the development of T-cell responses via their ability to release IL
      10.

PMID- 9921950
TI  - Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the
      vasculature of human pancreatic tumor biopsies.
AB  - Cellular nitric oxide (NO) synthesis determines whether NO has cytoprotective or
      cytotoxic effects at anatomic sites; thus it is important to identify potential
      NO synthase isoforms in tumor tissue and tumor cell lines which might be involved
      in tumor development or destruction. Incubation of human pancreatic
      adenocarcinoma cell lines (AsPc-1, BxPc-3, CaPan-2) with cytokines resulted in
      increased NO formation, indicating the existence of the NOS2 isoform. This was
      confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western
      blot analysis. Furthermore, we identified the presence of the endothelium-derived
      NOS isoform 3 by RT-PCR analysis and immunohistochemistry in normal and
      pancreatic tumor biopsies. NOS3 was markedly overexpressed in the vasculature of
      the tumor tissue. RT-PCR analysis of tumor biopsies identified NOS isoform 2 mRNA
      in 60% of cases, but western blot analysis or immunohistochemistry scored
      negative for this isoform. It is noteworthy that the NOS enzyme activity in
      pancreatic tumor cell lines and tumor biopsies was inhibited by EGTA by
      approximately 30% and 65%, respectively. Our results suggest that increased
      endothelium-derived NOS isoform 3 expression in pancreatic adenocarcinomas
      regulates blood flow and is therefore involved in the vascularization and
      neovascularization of human pancreatic tumors.

PMID- 9921951
TI  - Drug prophylaxis of deep vein thrombosis in traumatology: is there a benefit of a
      score in outpatients?
AB  - INTRODUCTION: Guidelines are lacking for the administration of drug prophylaxis
      of deep vein thrombosis (DVT) in outpatients. This study attempted to develop
      such a guideline in the form of a score. PATIENTS AND METHODS: In a prospective
      study of 731 outpatients with injury or surgery of the leg or pelvis a score was
      assigned based on "simulated physiological conditions" of the venous flow,
      including breathing, mobilization (activity of daily live), weight bearing and
      range of motion of joints of the lower extremities, lesions of the venous
      endothelium, date of injury, and localization of injury. The decision as to
      whether to administer drug prophylaxis of DVT was made on the basis of the
      patient's score. The venous system was investigated by duplex color-coded
      ultrasound. RESULTS: There were two false-negative findings, meaning that
      patients without drug prophylaxis showed a thrombotic complication. In neither of
      these cases had the patient been compliant with medical instructions. In the
      group with drug prophylaxis there were 4% DVT (n=18). CONCLUSION: Compared to
      previous results of 10% DVT in outpatients, our score-assisted drug prophylaxis
      significantly reduced the incidence of DVT. The score also makes it possible to
      select patients not requiring drug prophylaxis.

PMID- 9921952
TI  - Gastric substitute after total gastrectomy--clinical relevance for reconstruction
      techniques.
AB  - BACKGROUND: More than 60 different methods of reconstruction after total
      gastrectomy have been described. The different surgical procedures can be reduced
      essentially to pouch reconstruction, pouch size and maintenance of duodenal
      passage. METHODS: To clarify the importance of pouch reconstruction and
      maintenance of duodenal passage, we reviewed all controlled prospectively
      randomized clinical studies reporting on the various methods of reconstruction
      after gastrectomy. RESULTS: After reconstruction with a pouch, 6-month
      postoperative patients have a better food intake, a slower food passage (t50% 12
      vs 25 min), fewer postprandial symptoms (4-10% vs 20-60%), less weight loss (7 vs
      14 kg), and in tendency, they have a better quality of life. With maintenance of
      duodenal passage, disturbance of blood sugar regulation (stimulated glucose level
      22% lower) and iron deficiency anemia (hemoglobin: 13.9 vs 12.5 g/dl; iron: 18.4
      vs 10.2 micromol/l) are prevented. In addition, the patients lose less body
      weight (8% higher) and they tend to have a better quality of life (life quality
      score: 84 vs 76 points). Nevertheless, in several studies the number of patients
      is too small to demonstrate significant differences. CONCLUSIONS: After total
      gastrectomy, curatively operated patients might benefit from a reconstruction
      with pouch and maintenance of duodenal passage. Nevertheless, the present study
      results are partially divergent. For definitive demonstration of the superiority
      of this technique, further controlled longitudinal studies should be conducted
      with a larger number of cases and suitable instruments for assessing the quality
      of life.

PMID- 9921953
TI  - Alcohol consumption and risk of breast cancer: the Framingham Study revisited.
AB  - Although many studies report that moderate-to-heavy alcohol intake increases
      breast cancer risk, the effect of light alcohol consumption remains
      controversial, and a consistent pattern of association with different types of
      alcoholic beverages is not evident. The authors examined the relation of average
      alcohol consumption and of different beverages to the risk of breast cancer in
      the Framingham Study (Framingham, Massachusetts). Of 2,764 women followed more
      than 40 years in the Original Cohort from 1948 to 1993 and 2,284 followed up to
      24 years in the Offspring Cohort from 1971 to 1993, 221 and 66 incident breast
      cancer cases occurred, respectively. Breast cancer incidence decreased from 3.60
      per 1,000 person-years to 2.47, 2.30, and 2.33 in increasing categories of
      average alcohol consumption (none, < 5.0, 5.0-< 15.0, and > or = 15.0 g/day)
      among the Original Cohort and from 3.07 to 1.26, 1.24, and 2.22, respectively,
      among the Offspring Cohort. With the two cohorts combined, multivariate-adjusted
      rate ratios of breast cancer in each increased category of alcohol consumption
      were 1.0 (nondrinkers), 0.8 (95% confidence interval (CI) 0.6-1.1), 0.7 (95% CI
      0.5-1.1), and 0.7 (95% CI 0.5-1.1), respectively. Breast cancer was not
      associated with wine, beer, or spirits consumption when assessed separately. The
      findings suggest that the light consumption of alcohol or any type of alcoholic
      beverage is not associated with increased breast cancer risk.

PMID- 9921954
TI  - The Framingham results on alcohol and breast cancer.

PMID- 9921955
TI  - Alcohol consumption, cigarette smoking, and risk of benign prostatic hyperplasia.
AB  - Alcohol consumption and cigarette smoking were evaluated in relation to
      development of benign prostatic hyperplasia (BPH) among 29,386 members of the
      Health Professionals Follow-up Study. Men who were 40-75 years old in 1986 and
      free of prior BPH surgery, diagnosed cancer at baseline, and prostate cancer at
      baseline and during follow-up were followed for incidence of BPH surgery from
      1986 to 1994. Cases were men who reported BPH surgery between 1986 and 1994 (n =
      1,813) or who scored > or = 15 points of 35 on seven lower urinary tract symptom
      questions modified from the American Urological Association symptom index in 1992
      and 1994 (n = 1,786); noncases were men who scored < or = 7 points (n = 20,840).
      After controlling for age, race/ethnicity, body mass index, physical activity,
      and mutually for alcohol intake and smoking, moderate alcohol consumption was
      inversely related with total BPH (30.1-50 g/day vs. 0: odds ratio (OR) = 0.59,
      95% confidence interval (CI) 0.51-0.70; p trend < 0.0001), although the relation
      was attenuated at high intake (> or = 50.1 g/day vs. 0: OR = 0.72, 95% CI 0.57
      0.90). Current cigarette smoking was positively related to total BPH only among
      those who smoked 35 or more cigarettes/day (compared with never smokers: OR =
      1.45, 95% CI 1.07-1.97). These findings suggest that moderate alcohol consumption
      and avoidance of smoking may benefit BPH.

PMID- 9921956
TI  - Psychological disorder and mortality in French older adults: do social relations
      modify the association?
AB  - The possible modifying effect of social relations on the association between
      depression and mortality was examined in a community-based cohort study. A total
      of 3,777 randomly selected persons 65 years of age and older in southwest France
      were followed over a 5-year period from 1988 in the Personnes Agees Quid
      (PAQUID). At study entry, the prevalence of elevated depressive symptomatology
      was 12.9% for men and 14.7% for women, and the reported relative isolation was
      14.1% for men and 26.0% for women. During a total of 16,984 person-years of
      follow-up, 849 deaths occurred. Among participants with high levels of depressive
      symptomatology, the age-adjusted mortality rate ratio was 2.10 (95% confidence
      interval 1.7-2.7) in men and 1.76 (95% confidence interval 1.4-2.3) in women.
      When compared with individuals with the most connections, men and women with few
      social network connections were also at increased risk of mortality: age-adjusted
      rate ratio = 2.69 (95% confidence interval 1.9-3.8) for men and 1.56 (95%
      confidence interval 1.0-2.4) for women. Satisfaction with social support had a
      small but nonsignificant effect on mortality risk. For women, the excess risks
      due to depressive symptoms and few network connections are observed only in the
      65- to 74-year age group, after adjusting for health and health behaviors. Social
      relations did not significantly modify the depression-mortality associations for
      either men or women, although the depression-mortality effect was reduced by
      12.8% in men. The latter findings do not appear to be compatible with the
      buffering hypothesis, whereby we would expect social relations to decrease the
      depression-mortality association. Nonetheless, there are independent effects from
      these two factors, and older men who are depressed and not socially connected are
      at increased risk of dying earlier.

PMID- 9921957
TI  - Psychological stress in the workplace and menstrual function.
AB  - The relation between psychological stress at work and menstrual function was
      examined for 276 healthy, working, premenopausal women who participated in the
      California Women's Reproductive Health Study in 1990-1991. Subjects collected
      daily urine samples and completed a daily diary for an average of five menstrual
      cycles. Metabolites of estrogen and progesterone were measured in the urine, and
      computer algorithms were developed to characterize each cycle as ovulatory or
      anovulatory and to select a probable day of ovulation. A telephone interview
      collected information about psychological stress at work as well as other
      occupational, demographic, lifestyle, and environmental factors. Logistic
      regression was used to model stressful work and risk of anovulation (> or = 36
      days without ovulating) and measures of within-woman cycle variability. Repeated
      measures analyses were performed on other menstrual cycle parameters. Stressful
      work (high demand in combination with low control) was not strongly related to an
      increased risk for anovulation or cycle variability or to any of the following
      cycle endpoints: short luteal phase (< or = 10 days), long follicular phase (> or
      = 24 days), long menses (> or = 8 days), or long cycle (> or = 36 days). However,
      women in stressful jobs had a more than doubled risk for short cycle length (< or
      = 24 days) compared with women not working in stressful jobs (adjusted odds ratio
      = 2.24, 95% confidence interval 1.09-4.59).

PMID- 9921958
TI  - Magnetic field exposure and cardiovascular disease mortality among electric
      utility workers.
AB  - Laboratory studies suggest that electric and magnetic field exposure may affect
      heart rate and heart rate variability. Epidemiologic evidence indicates that
      depressed heart rate variability is associated with reduced survival from
      coronary heart disease as well as increased risk of developing coronary heart
      disease. The authors examined mortality from cardiovascular disease in relation
      to occupational magnetic field exposure among a cohort of 138,903 male electric
      utility workers from five US companies over the period 1950-1988. Cardiovascular
      disease deaths were categorized as arrhythmia related (n = 212), acute myocardial
      infarction (n = 4,238), atherosclerosis (n = 142), or chronic coronary heart
      disease (n = 2,210). Exposure was classified by duration of work in jobs with
      elevated magnetic field exposure and indices of cumulative magnetic field
      exposure. Adjusting for age, year, race, social class, and active work status,
      longer duration in jobs with elevated magnetic field exposure was associated with
      increased risk of death from arrhythmia-related conditions and acute myocardial
      infarction. Indices of magnetic field exposure were consistently related to
      mortality from arrhythmia and acute myocardial infarction, with mortality rate
      ratios of 1.5-3.3 in the uppermost categories. No gradients in risk were found
      for atherosclerosis or for chronic coronary heart disease. These data suggest a
      possible association between occupational magnetic fields and arrhythmia-related
      heart disease.

PMID- 9921959
TI  - Increasing number and incidence of fall-induced severe head injuries in older
      adults: nationwide statistics in Finland in 1970-1995 and prediction for the
      future.
AB  - To increase knowledge about recent trends in the number and incidence of various
      fall-induced injuries among older adults, the authors selected from the National
      Hospital Discharge Register all patients 60 years of age or older who were
      admitted to hospitals in Finland for primary treatment of a first fall-induced
      severe head injury during 1970-1995. Similar patients aged 30-39 years served as
      a reference group. For the study period, the number and incidence (per 100,000
      persons) of fall-induced severe head injuries in Finnish persons 60 years of age
      or older increased considerably (554 and 85, respectively, in 1970 compared with
      1,393 and 144, respectively, in 1995). The age-adjusted incidence of these
      injuries also increased in women, from 80 in 1970 to 125 in 1995, and in men,
      from 102 in 1970 to 147 in 1995. In the reference group (patients aged 30-39
      years), the absolute numbers and incidences of similar injuries did not show
      consistent trend changes over time. We conclude that the number of fall-induced
      severe head injuries in elderly Finnish women and men is increasing at a rate
      that cannot be explained simply by demographic changes, and therefore vigorous
      preventive measures should be instituted at once to control the increasing burden
      of these devastating injuries.

PMID- 9921961
TI  - Coffee and tea intake and the risk of myocardial infarction.
AB  - The authors investigated the association of caffeinated coffee, decaffeinated
      coffee, and tea with myocardial infarction in a study of 340 cases and age-, sex
      , and community-matched controls. The odds ratio for drinking > or = 4 cups/day
      of caffeinated coffee versus drinking < or = 1 cup/week was 0.84 (95% confidence
      interval (CI) 0.49-1.42) after adjustment for coronary risk factors (1 cup = 237
      ml). The odds ratio for drinking > 1 cup/day of decaffeinated coffee versus
      nondrinkers was 1.25 (95% CI 0.76-2.04). For tea, the odds ratio for drinking >
      or = 1 cup/day versus nondrinkers was 0.56 (95% CI 0.35-0.90). In these data,
      only tea was associated with a lower risk of myocardial infarction.

PMID- 9921960
TI  - Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease
      mortality among postmenopausal women.
AB  - To investigate whether greater intakes of calcium, vitamin D, or milk products
      may protect against ischemic heart disease mortality, the authors analyzed data
      from a prospective cohort study of 34,486 postmenopausal Iowa women 55-69 years
      old and without a history of ischemic heart disease who completed a dietary
      questionnaire in 1986. Through 1994, 387 deaths due to ischemic heart disease
      were documented (International Classification of Diseases, Ninth Revision, codes
      410-414, 429.2). The multivariate-adjusted relative risks for the highest versus
      the lowest quartiles of total calcium, vitamin D, and milk product intakes were
      as follows: 0.67 (95% confidence interval (CI) 0.47-0.94; p for trend = 0.09) for
      calcium, 1.41 (95% CI 0.93-2.15; p for trend = 0.12) for vitamin D, and 0.94 (95%
      CI 0.66-1.35; p for trend = 0.68) for milk products. The relative risk was 0.63
      (95% CI 0.40-0.98) for high dietary calcium but no supplemental calcium intake
      and 0.66 (95% CI 0.36-1.23) for high supplemental calcium but low dietary calcium
      intake. These results suggest that a higher intake of calcium, but not of vitamin
      D or milk products, is associated with reduced ischemic heart disease mortality
      in postmenopausal women, and reduced risk may be achievable whether the higher
      intake of calcium is attained by diet, supplements, or both.

PMID- 9921962
TI  - Diabetes mellitus and serum carotenoids: findings from the Third National Health
      and Nutrition Examination Survey.
AB  - Little is known about carotenoids, a diverse group of plant compounds with
      antioxidant activity, and their association with diabetes, a condition
      characterized by oxidative stress. Data from phase I of the Third National Health
      and Nutrition Examination Survey (1988-1991) were used to examine concentrations
      of alpha-carotene, beta-carotene, cryptoxanthin, lutein/zeaxanthin, and lycopene
      in 40- to 74-year-old persons with a normal glucose tolerance (n = 1,010),
      impaired glucose tolerance (n = 277), newly diagnosed diabetes (n = 148), and
      previously diagnosed diabetes (n = 230) based on World Health Organization
      criteria. After adjustment for age, sex, race, education, serum cotinine, serum
      cholesterol, body mass index, physical activity, alcohol consumption, vitamin
      use, and carotene and energy intake, geometric means of beta-carotene were 0.363,
      0.316, and 0.290 micromol/liter for persons with a normal glucose tolerance,
      impaired glucose tolerance, and newly diagnosed diabetes, respectively (p = 0.004
      for linear trend), and geometric means for serum lycopene were 0.277, 0.259, and
      0.231 micromol/liter, respectively (p = 0.044 for linear trend). All serum
      carotenoids were inversely related to fasting serum insulin after adjustment for
      confounders (p < 0.05 for each carotenoid). If confirmed, these data suggest new
      opportunities for research that include exploring a possible role for carotenoids
      in the pathogenesis of insulin resistance and diabetes.

PMID- 9921963
TI  - Infant and child growth and fatness and fat distribution in Guatemalan adults.
AB  - To examine whether poor growth in utero or young childhood is associated with
      adult abdominal fatness in a developing country context, the authors analyzed
      prospectively collected data on 372 female and 161 male Guatemalans measured as
      children between 1969 and 1977 and remeasured as adults in 1988-1989 (men and
      women) and 1991-1994 (women only). Childhood stunting (height-for-age z score)
      was associated with a lower body mass index and percent body fat in men, while no
      associations were found in women. In both sexes, however, severely stunted
      children had significantly greater adult abdominal fatness (waist:hip ratio),
      once overall fatness and confounders were controlled. The adult waist:hip ratio
      (x100) was increased by 0.65 (95% confidence interval 0.10 to 1.20) in men and
      0.29 (95% confidence interval -0.03 to 0.61) in women for each height-for-age z
      score less at age three. Migration to urban centers was significantly associated
      with an even greater waist:hip ratio in severely stunted females (p = 0.03). In a
      subsample of 137 women, short and thin newborns had significantly greater adult
      abdominal fatness compared with long and thin or short and fat newborns or
      children who became stunted postnatally. The adult waist:hip ratio (x100) was
      increased by 1.58 (95% confidence interval 0.35 to 2.81) for each kilogram less
      birth weight. The authors conclude that, in countries where maternal and child
      malnutrition exists alongside rapid economic development and urban migration,
      abdominal obesity and related chronic diseases are likely to increase.

PMID- 9921964
TI  - Quality of HMO vaccination databases used to monitor childhood vaccine safety.
      Vaccine Safety DataLink Team.
AB  - The availability of large, population-based, automated, medical care databases
      provides unique opportunities for monitoring the safety of childhood vaccines.
      The authors assessed the quality of automated vaccination databases by comparing
      them with vaccinations documented in paper-based medical records at three large
      US West Coast health maintenance organizations (HMOs) participating in the
      Vaccine Safety DataLink (VSD) study, a Centers for Disease Control and Prevention
      collaborative study of childhood vaccine safety. The authors randomly selected 1%
      or 2% samples of VSD study populations (n = 1,224-2,577) for data quality
      analyses. Agreement between automated and abstracted vaccinations required
      identical triads of child identification number, vaccination date, and vaccine
      type. Separate analyses were conducted for each HMO and for each vaccine type
      administered between 1991 and 1995. Agreement was measured by three matching
      proportions: 1) the proportion of automated vaccinations present in the
      abstracted source, 2) the proportion of abstracted vaccinations present in the
      automated source, and 3) the proportion of vaccinations from either source
      present in both sources. Overall, for common childhood vaccines, proportion 1
      ranged from 83% to 99%, proportion 2 ranged from 82% to 98%, and proportion 3
      ranged from 70% to 97%. Lack of automated data was the most frequent type of
      discrepancy, followed by date mismatches and vaccine type mismatches. Vaccination
      exposure classification errors in the range reported here were found by
      mathematical modeling to only modestly bias measured medical outcome rate ratios
      toward the null hypothesis. The results of the data quality analyses support the
      usefulness of vaccination exposure data derived from these automated HMO
      vaccination databases.

PMID- 9921965
TI  - Factors influencing the optimal control-to-case ratio in matched case-control
      studies.
AB  - Statistical power in matched case-control studies depends on both the correlation
      coefficient between cases and their matched controls (phi) and the prevalence of
      exposure among controls (P0). To examine the hypothesis that the value of
      increasing the control-to-case ratio beyond 5 varies with both phi and P0, the
      authors estimated statistical power for a hypothetical case-control study under
      different assumptions. The effect of increasing the control-to-case ratio
      depended on phi and, to a lesser extent, on P0. The results suggest that
      investigators consider including more than five controls per case when either phi
      is greater than about 0.2 or P, is less than about 0.15.

PMID- 9921966
TI  - Re: "The genetic passport".

PMID- 9921967
TI  - Medical oncology: its origin, evolution, current status, and future.
AB  - BACKGROUND: Over the last 26 years, the subspecialty of medical oncology has been
      evolving, and in the process bringing to the community improved oncologic
      management. During this evolution, guidelines for training new members of the
      subspecialty have been developed, and these have been heralded as important
      strides forward in medical education. Continual adjustment to new technology and
      changing population needs represent challenges for the future. METHODS: The steps
      in the development of this subspecialty, which are documented in educational
      publications, are reviewed in this article. RESULTS: Medical oncology evolved
      because of the introduction of multiple new cancer therapies and an awareness of
      the need of patients with cancer for continual care, from diagnosis to the end-of
      life phase. Together, certified medical oncologists represent the third largest
      of the current subspecialties of internal medicine. Training guidelines and the
      needs of the work force are being continually assessed in an effort to maintain
      an important future for these specialists. CONCLUSIONS: Medical oncologists are
      cancer specialists who are not in competition with primary care physicians, but
      are instead supportive. By serving as principal caregivers (those subspecialists
      who provide most of a patient's health care needs), and by paying increasing
      attention to older patients with cancer, medical oncologists will remain in
      demand.

PMID- 9921968
TI  - Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome
      after local treatment.
AB  - BACKGROUND: Although antibiotic therapy is emerging as effective initial
      treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue
      (MALT), there is a subset of patients for whom antibiotics are ineffective or
      inappropriate. Surgical resection can be curative, but total gastrectomy may be
      required for the eradication of all disease. To identify the optimal
      nonantibiotic therapy for early stage gastric MALT lymphoma, the authors
      retrospectively evaluated the Massachusetts General Hospital experience with
      gastric MALT lymphoma. METHODS: Disease patterns and treatment outcomes were
      retrospectively analyzed in data from 21 consecutive patients with gastric MALT
      lymphoma who were treated between 1978 and 1995 at the Massachusetts General
      Hospital. RESULTS: Sixteen patients were Stage IE, and 5 were in higher stages.
      Treatment consisted of resection with or without radiation or chemotherapy (14
      patients), radiation alone (4 patients), or radiation plus chemotherapy (2
      patients). Thirteen Stage IE patients received local therapy only. The 10-year
      actuarial relapse free survival rate for Stage IE patients was 93%, with 1
      relapse among 15 treated patients. Because the patient who relapsed was treated
      successfully with chemotherapy, the 10-year cancer free survival was 100%.
      Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years,
      with no deaths from lymphoma. CONCLUSIONS: These data indicate that a high
      probability of long term remission can be achieved with only local treatment of
      patients with Stage I gastric MALT lymphoma. Preliminary results suggest that
      radiation therapy is well tolerated and effective and may well be the optimal
      nonantibiotic treatment for patients with localized gastric MALT lymphoma.

PMID- 9921969
TI  - Possible paracrine mechanism of insulin-like growth factor-2 in the development
      of liver metastases from colorectal carcinoma.
AB  - BACKGROUND: Insulin-like growth factor-2 (IGF-2) is considered one of the
      autocrine growth factors in colorectal carcinoma. In addition, it is well known
      that IGF-2 is produced in the liver. However, the role of IGF-2 in liver
      metastasis is not yet understood clearly. METHODS: Immunohistochemical staining
      of IGF-2 and IGF-1 receptor (IGF-1R) was performed on tissue samples of liver
      metastases from 30 colorectal carcinoma patients. In situ hybridization of IGF-2
      also was conducted on the same tissue samples. Furthermore, proliferating cell
      nuclear antigen (PCNA) was immunohistochemically stained for use as an indicator
      of the proliferative activity of cancer cells. RESULTS: Invasive margins of liver
      metastases were stained highly by both IGF-2 (70%) and IGF-1R (83%).
      Overexpression of IGF-2 protein and mRNA was observed in the normal liver
      adjacent to the tumor. The PCNA labeling indices (LIs) of the IGF-2 positive
      groups were significantly higher than those of the IGF-2 negative group (P <
      0.0001). In addition, the PCNA LIs for the IGF-1R positive groups also were
      significantly higher than those for the IGF-1R negative group (P=0.0002).
      CONCLUSIONS: These findings suggest that hepatocyte-derived IGF-2 stimulates
      tumor cell proliferation by a paracrine mechanism and plays an important role in
      tumor progression in colorectal carcinoma patients with liver metastases.

PMID- 9921970
TI  - Treatment of anal carcinoma in the elderly: feasibility and outcome of radical
      radiotherapy with or without concomitant chemotherapy.
AB  - BACKGROUND: For most cancers, information on treatment tolerance and results for
      elderly patients is quite limited. This study was conducted to investigate the
      feasibility and results of curative nonsurgical treatment of patients age 75
      years or older with anal carcinoma. METHODS: From January 1976 through June 1996,
      invasive anal squamous cell carcinoma was diagnosed in 58 patients age > or = 75
      years. Curative treatment was administered to 47 patients (81%), of whom 42
      received radiotherapy (RT), either used alone (21) or associated with concomitant
      chemotherapy (CT). RT was administered in two sequences, the first in which a
      median dose of 39.6 gray (Gy) was delivered with megavoltage photon beams,
      followed (after a median interval of 43 days) by a boost with either
      brachytherapy or external beam (median dose, 20 Gy). CT started on Day 1 and
      generally consisted of 1 cycle of mitomycin C (MMC; median dose, 9.5 mg/m2) and a
      96-hour infusion of 5-fluorouracil (5-FU; median dose, 600 mg/m2/day). The median
      follow-up for all patients was 48 months (range, 5-163 months). RESULTS: Of 40
      patients (95%) who completed curative treatment, acute toxicity resulted in
      shortening of the planned first irradiation sequence in 2 patients (1 in each
      group) and an unplanned treatment break in 11 patients (4 in the RT group and 7
      in the RT-CT group). Grade 2 and 3 acute reactions (RTOG) were observed in 43%
      and 54% of patients, respectively. Among all Grade 3 reactions, 32% occurred in
      the RT group and 68% in the RT-CT group. In patients receiving RT-CT, Grade 2-3
      leukopenia was observed in 25% of patients, Grade 2-3 fatigue was observed in 58%
      of patients, and Grade 2 cardiac toxicity related to 5-FU occurred in 1 patient.
      At 5 years, the overall survival was 54% (49% and 59% for the RT and RT-CT
      groups, respectively, P = 0.28), and the actuarial local control rate was 78.5%
      (73% and 83% for the RT and RT-CT groups, respectively, P=0.36). Five patients
      presented with Grade 3-4 late complications, all of them in the RT-CT group.
      CONCLUSIONS: The current series confirms the feasibility of sphincter-conserving
      treatment for elderly patients who present with anal carcinoma. Rates of acute or
      late complications appeared similar to those observed in younger patients, and
      the oncologic results were at least as favorable as those commonly reported.

PMID- 9921971
TI  - Melanoma of the gallbladder: a review of cases seen at Duke University Medical
      Center.
AB  - BACKGROUND: Both primary and metastatic melanoma of the gallbladder are rare. In
      cases involving isolated tumors of the gallbladder, there continues to be
      controversy regarding the establishment of primary status. Despite appropriate
      therapy, the diagnosis of either condition portends a poor prognosis, with few
      patients surviving more than 2 years. METHODS: A review of all patients seen at
      Duke University Medical Center since 1970 generated 1 case of primary and 19
      cases of secondary melanoma of the gallbladder. These were analyzed with respect
      to presentation, clinical and pathologic diagnosis, treatment, and prognosis.
      RESULTS: The sole patient with a primary lesion presented with acute
      cholecystitis. Ultrasound demonstrated a mass in the lumen of the gallbladder.
      Cholecystectomy revealed melanoma, and the patient eventually died of
      disseminated disease 13.5 months later. Survival was poor for patients who
      presented with metastases to the gallbladder in the setting of widespread
      disease, with 0% survival at 1 year (n=11). Those with isolated, resectable
      lesions fared better overall, with 100% survival (n=6) at 1 year. One patient
      remains alive and free of disease 13.8 years later, which, to our knowledge,
      represents the longest documented survival for a patient with melanoma that has
      metastasized to the gallbladder. CONCLUSIONS: Surgery remains the mainstay of
      therapy for patients with gallbladder melanoma and appears to improve patient
      outcome in the setting of resectable disease. Hopefully, further investigations
      will lead to standardized protocols for the treatment of these lesions.

PMID- 9921972
TI  - A multimodal strategy for the treatment of patients with T2 invasive squamous
      cell carcinoma of the glottis.
AB  - BACKGROUND: The current conservative standard of care for T2 squamous cell
      carcinoma of the glottis is either partial laryngectomy or radiation therapy.
      METHODS: Based on an inception cohort of 100 patients with T2 squamous cell
      carcinoma of the glottis and a minimum of 3 years of follow-up, the present study
      documented the results achieved with a multimodal strategy using platinum-based
      induction chemotherapy and partial laryngeal surgery. Statistical analysis of
      survival and local control was based on the Kaplan-Meier actuarial life table
      method. Univariate analysis was performed to determine whether there was a
      correlation among various factors and toxicity, clinical response, histologic
      regression, local control, and survival. RESULTS: A complete clinical response
      and a partial response after induction chemotherapy was achieved in 24% and 58%
      of patients, respectively. Complete histologic regression was noted in 31%. A
      significant statistical relation (P < 0.0001) was noted between a complete
      clinical response after induction chemotherapy and a complete histologic
      regression. The 5-year actuarial survival estimate was 85.8%. The 5-year
      actuarial local control estimate was 95.7% (97.7% if the vocal cord was mobile
      and 93.8% if the motion of the vocal cord was impaired). Salvage treatment
      resulted in an overall 99% rate of local control and a 95% rate of laryngeal
      preservation. CONCLUSIONS: Because this represents a nonrandomized retrospective
      study, no definitive conclusions can be derived. However, when compared with the
      data reported in a large series using radiation therapy or partial laryngectomy
      alone, this 10-year experience suggests that, in patients with "early" invasive
      squamous cell carcinoma of the glottis, the use of platinum-based induction
      chemotherapy prior to a conventional conservative treatment modality should be
      investigated further.

PMID- 9921973
TI  - Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma: the
      role of gelsolin expression.
AB  - BACKGROUND: Tumor cell motility is an important characteristic that facilitates
      the multistep process of tumor metastasis. Rac, ABP-280, and gelsolin are
      proteins that interact with actin and are important in cell motility. METHODS:
      The authors studied a cohort of 229 Stage I nonsmall cell lung carcinoma (NSCLC)
      patients who had a minimum of 3 years follow-up and had been previously analyzed
      for 22 clinical, pathologic, and molecular features, of which 9 had been found to
      provide significant prognostic information in a Cox proportional hazards model.
      Tumor sections were stained by the avidin-biotin complex method using monoclonal
      antibodies against rac, ABP-280, and gelsolin. RESULTS: In a pilot analysis of
      over 50 patients each, rac and ABP-280 were found to be moderately-to-highly
      expressed in the majority of tumors and to provide no prognostic information.
      Gelsolin expression was more variable and appeared to be negatively correlated
      with survival in the pilot population. In the larger 229-patient population, high
      focal gelsolin expression was seen in 32 tumors (14%) and conferred the highest
      relative risk (4.04) of cancer recurrence among all factors tested, compared with
      tumors that had no or low gelsolin expression. Moderate focal gelsolin
      expression, seen in 46 patients (20%), also conferred a significant risk of
      cancer recurrence, with a relative risk of 2.26 compared with tumors that had no
      or low gelsolin expression. Consideration of average gelsolin expression and of
      overall survival yielded similar results. CONCLUSIONS: Gelsolin expression
      appears to be a significant prognostic factor for cancer recurrence in cases of
      Stage I NSCLC.

PMID- 9921974
TI  - Complete hematologic and cytogenetic response to 2-amino-9-beta-D-arabinosyl-6
      methoxy-9H-guanine in a patient with chronic myelogenous leukemia in T-cell
      blastic phase: a case report and review of the literature.
AB  - BACKGROUND: T-cell lymphoid blastic phase (BP) transformation is rare in chronic
      myelogenous leukemia (CML). 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine
      (GW506U78), a prodrug of arabinosylguanine (ara-G), is effective in T-cell
      leukemias. METHODS: The authors present a case of a 48-year-old male with
      Philadelphia chromosome (Ph) positive CML and T-cell lymphoid BP after 17 months
      in the chronic phase. RESULTS: Plasma pharmacokinetic studies after an infusion
      of GW506U78 at a dose of 40 mg/kg showed GW506U78 concentrations of 60 microM,
      and a peak ara-G concentration of 260 microM in the plasma. Cellular ara-G
      triphosphate (ara-GTP) concentration in the peripheral blood T-lymphoblasts was
      80 microM at the end of GW506U78 infusion and reached a maximum of 150 microM.
      The patient achieved a complete response that lasted 13 months. Severe
      neurotoxicity related to GW506U78 was observed. CONCLUSIONS: GW506U78 showed
      antileukemic activity against Ph positive T-cell BP CML. Neurotoxicity was dose
      limiting in this patient. Treatment with GW506U78 and modulation of ara-GTP
      concentrations are therapeutic strategies that require further exploration in T
      cell malignancies. Investigation of other dosing schedules may limit
      neurotoxicity.

PMID- 9921975
TI  - Long term outcome of patients with hairy cell leukemia treated with pentostatin.
AB  - BACKGROUND: With the introduction of new drugs such as interferon-alpha (IFN) and
      purine analogs, the management of hairy cell leukemia (HCL) patients has changed.
      However, pentostatin has been found to produce higher complete remission rates
      than IFN. The current study was undertaken to investigate response and long term
      follow-up in HCL patients treated with pentostatin. METHODS: Between March 1989
      and October 1996, 49 patients with HCL and 1 patient with a HCL variant were
      treated with pentostatin. Eighteen patients had received no prior therapy, 31
      patients had received prior treatment with IFN, and 1 patient had received prior
      treatment with 2'-chlorodeoxyadenosine (2'CdA) and IFN. All patients except 1
      were treated with a dose of 4 mg/m2 every 2 weeks. The median number of cycles
      was 12. RESULTS: The overall response rate was 96% (48 of 50 patients); 22
      patients (44%) achieved a complete response, 18 patients (36%) achieved a good
      partial response (defined as residual bone marrow infiltration < 5%), 8 patients
      (16%) achieved a partial response, and 2 patients died. For a median follow-up of
      33 months off therapy, there were 5 recurrences between 12-66 months; 3 of these
      patients were treated further with and responded to 2'CdA and 2 died of disease
      progression at 12 and 40 months, respectively. In addition, 3 patients died of
      unrelated causes (1 of very early infection, 1 of toxic death and another of
      cardiac arrest) comprising an overall death rate of 14% (7 of 50 patients). The
      overall survival rate was 86% for a median follow-up of 38 months (range, 8-105
      months). Major side effects were febrile episodes, herpes zoster, nausea/emesis,
      and pancytopenia. CONCLUSIONS: This analysis confirms both the high remission
      rate and durable responses that may be achieved with pentostatin treatment in HCL
      patients. Although pentostatin is active, the risk of cytopenia and
      immunosuppression must be evaluated carefully.

PMID- 9921976
TI  - The ABCD system of melanoma detection: a spectrophotometric analysis of the
      Asymmetry, Border, Color, and Dimension.
AB  - BACKGROUND: The ABCD (Asymmetry, Border, Color, and Dimension) criteria represent
      a commonly used clinical guide for the diagnosis of early melanoma. The authors
      revised these criteria in the light of objective measurements of the features of
      pigmented skin lesions obtained by telespectrophotometric analysis (TS) in the
      visible and near-infrared wavelengths. METHODS: This study involves a consecutive
      series of 186 patients with 195 cutaneous pigmented lesions (53 melanomas and 142
      nonmelanoma lesions). Each lesion was subjected to TS in vivo, before surgery.
      For this purpose, the authors used four spectrophotometric parameters that could
      be closely related to the four criteria of the ABCD guide, namely, roundness (an
      estimate of how a lesion contour resembles a circle), smoothness (an indicator of
      the regularity of a lesion border), mean reflectance (the ability of a lesion to
      diffuse or reflect the incident light), and size (the greatest dimension of a
      lesion). RESULTS: When melanomas and nonmelanoma lesions were compared by
      univariate analysis, all four spectrophotometric parameters considered proved to
      be significantly different (P=0.05). Multivariate logistic analysis showed that
      mean reflectance in the infrared (P < 0.01) and size (P=0.03) were parameters
      independently associated with melanoma. Melanoma showed lower reflectance and
      greater size than benign lesions. CONCLUSIONS: Information provided by TS
      substantially validates the importance of the ABCD clinical guide and suggests
      that color is the most important parameter in discriminating melanoma from nevi.
      In particular, melanoma appears darker than other pigmented lesions.

PMID- 9921977
TI  - Cardiac metastases from malignant melanoma.
AB  - BACKGROUND: Cardiac metastases are uncommon, with the exception of malignant
      melanoma. More cases of cardiac involvement are being diagnosed in association
      with the rising incidence and increasing survival of patients with melanoma.
      Surgical intervention may be an effective palliative measure and should be
      considered for selected patients who present with this problem. METHODS: In this
      article, the authors present clinical, laboratory, and imaging data from two
      patients with malignant melanoma who presented with cardiac metastases. A
      discussion of these patients is accompanied by a review of the current literature
      on this topic. RESULTS: Two females with known metastatic malignant melanoma
      presented with nonspecific pulmonary symptoms and were found to have intracardiac
      metastases involving the right heart. One patient underwent successful surgical
      removal of a large tumor mass, which resulted in relief of symptoms and
      prevention of imminent death from cardiac complications. Together with the
      literature review, these cases demonstrate the important clinical features of
      cardiac metastases from melanoma and define the best means of diagnosis as well
      as the potential benefits of surgical intervention. CONCLUSIONS: Cardiac
      involvement by malignant melanoma is now diagnosed with increasing frequency. A
      diagnosis can be made with relative ease, but clinical suspicion must precede it.
      Surgery may be useful to palliate symptoms and prevent death from cardiac
      complications.

PMID- 9921978
TI  - Patterns of recurrence in extremity liposarcoma: implications for staging and
      follow-up.
AB  - BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue
      sarcoma and presents a wide spectrum of clinical behavior. The authors examined
      the correlation among histologic subtypes, outcomes, and patterns of recurrence
      among patients with extremity liposarcomas. METHODS. A retrospective review of
      all patients with intermediate and high grade extremity liposarcoma referred to
      the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to
      December 31, 1992, was performed. Data on clinical presentation, treatment,
      patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13
      year study period, 122 patients with intermediate or high grade extremity
      liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients
      (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There
      were no differences between the myxoid and pleomorphic subtype groups in tumor
      size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The
      median follow-up was 70 months. The 5-year overall survival rate for all
      intermediate and high grade extremity liposarcoma patients presenting with
      primary disease (n=85) was 74%; the 5-year local recurrence free survival,
      distant recurrence free survival, and disease free survival rates were 93%, 78%,
      and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant
      recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the
      retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft
      tissue of the back), and 2 were to the lung only. Among the 18 patients with
      pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary
      sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic
      subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary
      sites and did so significantly more frequently than pleomorphic tumors. Imaging
      of the abdomen, retroperitoneum, and extrapleural chest should be performed for
      accurate staging and posttreatment follow-up of patients with myxoid liposarcoma.
      Patients presenting with "primary" myxoid liposarcoma of the trunk should be
      carefully evaluated for an occult primary tumor in an extremity.

PMID- 9921979
TI  - Survival after autologous hematopoietic stem cell transplantation for patients
      with inflammatory breast carcinoma.
AB  - BACKGROUND: The authors retrospectively determined the clinical outcome of
      patients with inflammatory breast carcinoma (IBC) treated with high dose
      chemotherapy (HDC) and autologous bone marrow (ABM) or peripheral blood stem cell
      (PBSC) support. METHODS: Twenty-four consecutive patients with IBC received HDC,
      including escalating doses of carboplatin (range, 1.2-1.8 g/m2) and
      cyclophosphamide (range, 4.8-6.0 g/m2) over 3 days followed by ABM (n=5) or PBSC
      infusion (n=19). Restaging evaluation was performed 100 days after transplant,
      every 6 months for 2 years, and then yearly thereafter. After transplantation,
      fifteen patients received immunotherapy with interleukin-2 (IL-2) or IL-2 and
      interferon-alpha. RESULTS: The 2-year estimated disease free survival (DFS) and
      overall survival (OS) for these patients were 71% (90% confidence interval [CI],
      55-87%) and 73% (90% CI, 53-93%), respectively. The median follow-up of surviving
      patients was 19 months (range, 8-68 months). Six patients developed disease
      recurrence at a median of 10 months (range, 4-16 months) after transplantation.
      Four of these 6 patients died from metastatic disease at a median of 18 months
      (range, 14-21 months). Using the generalized Wilcoxon test and the Cox
      proportional hazards regression model, patients with tumors that demonstrated
      estrogen receptors had an improved DFS (P=0.03). CONCLUSIONS: Combining HDC and
      ABM or PBSC for patients with IBC may yield an improved OS and DFS.

PMID- 9921980
TI  - Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in
      postmenopausal women with breast carcinoma.
AB  - BACKGROUND: Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonsteroidal
      aromatase inhibitor that significantly lowers estrogen levels in postmenopausal
      women and can be effective therapy for patients with advanced hormone-dependent
      breast carcinoma. Circulating estradiol, estrone, and estrone sulfate are reduced
      to undetectable levels within weeks of the initiation of therapy. Before this
      study, it was not known whether this decrease in serum estrogen levels results in
      altered parameters associated with cardiovascular disease. The authors examined
      the levels of several critical blood parameters that are important to
      cardiovascular risk for heart disease and thromboembolic disorders in patients
      treated with fadrozole. METHODS: Cholesterol, triglyceride, low density
      lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein
      (VLDL), antithrombin III, protein C, protein S, and fibrinogen were serially
      measured in 21 postmenopausal women with advanced breast carcinoma treated with
      various doses of fadrozole (1.8 mg/day, n=3; 2.0 mg/day, n=13; 4.0 mg/day, n=5)
      over 3-24 months (mean, 15.8 months). A repeated measure analysis of variance was
      applied to each cardiovascular variable to assess changes in the response over
      time. Analyses were performed separately for each dose group and were also pooled
      over the dose groups. RESULTS: There was no statistically significant change over
      time in lipid parameters, namely, total cholesterol (P=0.57), triglyceride
      (P=0.27), LDL (P=0.99), HDL (P=0.30), and VLDL (P=0.43), over the 24 months of
      therapy. There were also no significant changes in coagulation factors, namely,
      antithrombin III (P=0.41), protein C (P=0.49), or protein S (P=0.31), over the 24
      months. However, an increase in fibrinogen that occurred over time did reach
      statistical significance (P=0.011). CONCLUSIONS: With the exception of acute
      phase reactant fibrinogen, this study did not identify an increase in parameters
      associated with cardiovascular disease in women treated with fadrozole, a potent
      aromatase inhibitor.

PMID- 9921981
TI  - Results and long term follow-up for 1581 patients with metastatic breast
      carcinoma treated with standard dose doxorubicin-containing chemotherapy: a
      reference.
AB  - BACKGROUND: The authors report results and long term follow-up for 1581 patients
      with metastatic breast carcinoma treated with doxorubicin-containing combination
      chemotherapy at a single institution; this report is meant to serve as a reliable
      reference for single-arm studies of newer therapies in this patient population.
      METHODS: Prospectively collected data from 18 successive doxorubicin-containing
      protocols for the treatment of metastatic breast carcinoma were evaluated.
      RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%),
      complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response
      (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS)
      was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was
      21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to
      therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the
      patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR
      patients (n=766). The median OS of patients who had progressive disease during
      chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number
      of organs involved and especially with tumor burden. Patients with hormone
      receptor-positive tumors had a similar response rate to that of patients with
      hormone receptor negative tumors but had significantly longer PFS (medians of
      14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months,
      respectively). CONCLUSIONS: In patients with metastatic breast carcinoma,
      doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of
      16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all
      responders and 22.4 months and 41.8 months, respectively, for those who had CR.

PMID- 9921982
TI  - Global DNA hypomethylation in breast carcinoma: correlation with prognostic
      factors and tumor progression.
AB  - BACKGROUND: The global DNA methylation of 136 breast lesions (117 primary
      invasive carcinomas, 5 benign phyllodes tumors, 11 fibroadenomas, and 3
      sclerosing adenosis) and their respective adjacent parenchyma was analyzed using
      an in vitro enzyme assay. METHODS: In the group of patients with breast
      carcinoma, DNA hypomethylation was correlated with clinical and pathologic
      parameters known to affect disease prognosis. Histopathologic type, disease
      stage, and tumor grade were evaluated according to the World Health Organization
      classification, the TNM system, and the criteria of Elston and Ellis' criteria,
      respectively. DNA flow cytometry was performed in fresh/frozen samples stained
      with propidium iodide. Hormone receptor (estrogen and progesterone receptor)
      status was determined by immunocytochemistry. RESULTS: The comparative study of
      DNA methylation showed that the DNA of breast carcinomas was statistically
      significantly less methylated than the DNA of the respective adjacent parenchyma
      (P=0.0001), the DNA of breast benign lesions (P=0.0002), and the DNA of normal
      parenchyma (P < 0.0001). A statistically significant correlation was found
      between the global DNA hypomethylation and the disease stage (P=0.0009), tumor
      size (P=0.0026), and histologic grade (P=0.0097) of malignant neoplasms. A trend
      for DNA from breast carcinomas with positive axillary lymph nodes (N1) to be more
      hypomethylated than those without nodal involvement (NO) (P=0.055) was verified.
      In contrast, no significant association was found between DNA methylation and
      histologic type of tumors, hormone receptors, DNA ploidy, and S-phase fraction.
      CONCLUSIONS: The current shows that DNA hypomethylation is increased in breast
      carcinomas, playing a potentially important role in tumor development. These
      findings also suggest that DNA methylation status may be a biologic marker with
      prognostic significance in this group of neoplasms.

PMID- 9921984
TI  - Neurologic complications of ovarian carcinoma.
AB  - BACKGROUND: Neurologic complications of ovarian carcinoma are uncommon and to the
      authors' knowledge the full spectrum has not been delineated previously. METHODS:
      The authors reviewed the findings of 121 neurologic consultations on 83 ovarian
      carcinoma patients between 1993 and 1996; this represents 4% of all ovarian
      carcinoma patients seen at the study institution in this time period. RESULTS:
      The most common reasons for consultation were altered mental status, pain,
      weakness, numbness, headache, and seizure. Twenty-seven consultations diagnosed
      metastatic disease, 14 diagnosed cerebrovascular disease, and 4 diagnosed
      paraneoplastic syndromes; however, iatrogenic complications (n=38) comprised the
      majority of diagnoses. Greater than 50% of patients improved neurologically after
      diagnosis and treatment. CONCLUSIONS: Neurologic disease accompanying ovarian
      carcinoma may be more common and more diverse than recognized previously.
      Definitive neurologic diagnosis and treatment benefits the majority of patients.

PMID- 9921983
TI  - Differences in patterns of TP53 and KRAS2 mutations in a large series of
      endometrial carcinomas with or without microsatellite instability.
AB  - BACKGROUND: The correlation between tumor microsatellite instability (MSI) and
      the accumulation of mutations in KRAS2 and TP53 is uncertain. The authors
      evaluated the TP53 and KRAS2 genes for mutations in sporadic endometrial
      carcinomas with microsatellite instability (MSI) and matched MSI negative
      controls to determine whether defective DNA mismatch repair impacts the patterns
      of mutations in two genes known to be involved in endometrial tumorigenesis.
      METHODS: Twenty-five MSI positive endometrial tumors were matched for prognostic
      factors with 25 MSI negative tumors. Mutations in codon 12 and 13 of KRAS2 were
      assessed using a polymerase chain reaction (PCR) restriction assay. Mutations in
      codon 61 of KRAS2 and exons 5-8 of TP53 were evaluated using PCR amplification
      and single strand conformation variant (SSCV) analysis. All variants were
      subjected to direct DNA sequencing. RESULTS: KRAS2 and TP53 mutations were
      identified with equal frequency in the MSI positive and MSI negative groups. For
      TP53, the authors identified 5 mutations (20%) in the MSI positive specimens
      compared with 8 (32%) in the MSI negative group. For KRAS2, there were identified
      8 mutations (32%) in the MSI positive specimens compared with 7 (28%) in the MSI
      negative tumors. The mutational spectra evident from sequence analysis of TP53
      and KRAS2 variants were similar between MSI negative and MSI positive tumors. MSI
      negative tumors were more likely to have mutations in both KRAS2 and TP53 than
      MSI positive tumors, which were rarely mutant in both genes (P=0.046).
      CONCLUSIONS: Although the overall frequency of mutations in TP53 and KRAS2 is
      similar, MSI positive tumors are less likely to have mutations in both genes than
      MSI negative sporadic endometrial carcinomas. MSI positive and MSI negative
      endometrial carcinomas may arise through distinct genetic pathways.

PMID- 9921985
TI  - Blocking signaling through the Gp130 receptor chain by interleukin-6 and
      oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to
      etoposide and cisplatin-mediated cytotoxicity.
AB  - BACKGROUND: The mechanisms of drug resistance associated with advanced, hormone
      independent prostate carcinoma are poorly understood. The human prostate
      carcinoma PC-3 cell line, derived from a metastatic tumor and lacking androgen
      receptors, represents a useful model to investigate drug resistance. METHODS: The
      effects of oncostatin M (OM), antiinterleukin-6 (IL-6) treatment, or interference
      with the gp130-mediated signaling on etoposide- or cisplatin-mediated
      cytotoxicity were investigated. RESULTS: Both endogenous and exogenous IL-6 and
      exogenous OM up-regulated cell growth and enhanced resistance of PC-3 tumor cells
      to both etoposide and cisplatin. The influence of IL-6 is controlled by treating
      PC-3 tumor cells with anti-IL-6 neutralizing antibody and, more efficiently, by a
      mutated IL-6, Sant7. Sant7 has a high affinity binding to the IL-6 receptor-alpha
      (IL-6Ralpha) subunit, but does not bind to the signaling subunit gp130;
      therefore, it behaves as a receptor antagonist. Both IL-6- and OM-mediated
      effects are inhibited by the treatment of PC-3 with an antisense
      oligodeoxynucleotide against gp130, the protein kinase inhibitor genistein (GNS),
      or the monoterpene perillic acid (PA), a posttranslational inhibitor of p21ras
      isoprenylation. CONCLUSIONS: These results demonstrate the protective roles in
      drug sensitivity of IL-6 and OM through signaling of the common chain gp130 and,
      most likely, a downstream ras-dependent pathway in PC-3 tumor cells. These
      findings suggest the potential clinical application of anticytokine therapy or
      interference with gp130 signaling in the treatment of drug resistant prostate
      carcinoma.

PMID- 9921986
TI  - Evaluation of prostate needle biopsies in a population-based screening study: the
      impact of borderline lesions.
AB  - BACKGROUND: The finding of isolated high grade prostatic intraepithelial
      neoplasia (PIN) or borderline lesions (lesions suspicious for malignancy) in
      prostate needle biopsies warrants repeat biopsies. The reported frequency of
      these lesions in prostate needle biopsies varies considerably. The authors
      evaluated the frequency and clinical impact of high grade PIN and borderline
      lesions in sextant prostate needle biopsies obtained from screened participants
      in the European Randomized study of Screening for Prostate Cancer (ERSPC).
      METHODS: A total of 8763 participants in the Rotterdam section of the ERSPC ages
      55-75 years were screened systematically for prostate carcinoma. Systematic
      sextant prostate needle biopsies were prompted by an abnormal digital rectal
      examination and/or abnormal transrectal ultrasonography findings at serum
      prostate specific antigen (PSA) levels > or = 1.0 ng/mL or a PSA level > or = 4.0
      ng/mL. Repeat biopsies were obtained within 6 months after initial biopsy.
      RESULTS: Of 1824 biopsied men, 384 (21.1%) were found to have prostate carcinoma
      on initial biopsy. Twelve participants (0.7%) had isolated high grade PIN and 43
      (2.4%) had borderline lesions. Repeat biopsies yielded no carcinoma in 7
      participants with initial high grade PIN and 15 tumors (38.5%) in 39 participants
      with borderline lesions. CONCLUSIONS: In prostate needle biopsies obtained from a
      screened population, indications for repeat biopsy such as high grade PIN and
      borderline lesions do not represent large diagnostic subsets. Borderline lesions
      comprise the most important indication for a repeat biopsy. The low frequency of
      equivocal biopsy diagnoses in the current study supports the clinical
      applicability of sextant needle biopsies in population-based screening for
      prostate carcinoma.

PMID- 9921987
TI  - Is there a diagnostic role for bone scanning of patients with a high pretest
      probability for metastatic renal cell carcinoma?
AB  - BACKGROUND: The utility of performing whole-body bone scintigraphy (BS) as part
      of a routine staging workup for patients with renal cell carcinoma (RCC) is
      currently being debated. This study investigated the diagnostic performance of BS
      in 36 patients with a high pretest probability for bone metastases due to
      abnormal laboratory tests, pain, or confirmed nonosseous metastases. METHODS:
      Planar whole-body BS was performed in all patients 3 hours after the intravenous
      injection of 555 MBq (15 mCi) of technetium-99m-3,3-diphosphono-1,2-propane
      dicarboxylic acid tetrasodium salt). RESULTS: In 14 of 36 patients, bone
      metastases could be confirmed either due to computed tomography or magnetic
      resonance imaging (n=11) or open site directed biopsy (n=3), respectively. The
      sensitivity ranged from 10% to 60%, depending on the applied visual threshold.
      The extent of the metastatic involvement was underestimated in all cases. No
      diagnostic pattern of tracer accumulation, clinical features, or laboratory tests
      was identified as enhancing the sensitivity for the detection of bone metastases
      in this population. CONCLUSIONS: The authors concluded that, even among
      preselected patients, BS has no diagnostic role in RCC and should therefore be
      omitted from the clinical workup.

PMID- 9921988
TI  - Nuchal-type fibroma: a clinicopathologic study of 52 cases.
AB  - BACKGROUND: Nuchal-type fibroma (NTF) usually arises in the posterior aspect of
      the neck. Previously published reports describe only 11 cases and provide limited
      clinicopathologic information. METHODS: Fifty-two examples of NTF from 50
      patients were analyzed from the files of the Soft Tissue Registries of the Armed
      Forces Institute of Pathology in Washington, DC, and the Faculty Hospital in
      Pilsen, Czech Republic. RESULTS: The age of the patients ranged from 3 to 74
      years (mean, 40 years). There were 41 males and 9 females. Thirty-six NTFs were
      located in the posterior neck region and 16 were from extranuchal sites. Two
      patients had had lesions excised from both a nuchal and an extranuchal location.
      The mean greatest tumor dimension was 3.2 cm. Microscopically, all examples had a
      superficial (subcutaneous and sometimes dermal) component and consisted of
      paucicellular, thick bundles of lobulated collagen fibers with inconspicuous
      fibroblasts. Entrapped adipose tissue and traumatic neuromalike nerve
      proliferations were typically present. Skeletal muscle infiltration was also seen
      in a minority of cases. Eleven of 25 patients (44%) for whom clinical information
      was available reportedly had diabetes. Gardner's syndrome was documented in one
      patient and was possibly present in two additional individuals. During follow-up,
      five patients had local recurrences, but none of the recurrences were destructive
      and all were ultimately controlled by local reexcision. CONCLUSIONS: NTF is a
      rare, tumorlike accumulation of collagen that often affects the posterior neck
      region but can also occur in a number of other sites. The process has a strong
      association with diabetes and also appears to be linked to Gardner's syndrome.
      Local recurrence probably reflects the persistence of local or systemic factors
      related to its pathogenesis.

PMID- 9921989
TI  - Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Inhibition of apoptosis, or programmed cell death, may be critical
      both in the development of cancer and in determining response to therapy. The
      authors examined the expression of two related apoptotic inhibitors, Bcl-2 and
      Bcl-xL, in pretreatment biopsies from a series of 42 patients with squamous cell
      carcinoma of the head and neck. The observed pattern of apoptotic inhibitor
      expression was compared with that of the p53 gene product, another factor
      implicated in carcinogenesis and therapeutic responsiveness. METHODS: Formalin
      fixed, paraffin embedded tumor biopsies from 42 patients with locally advanced
      squamous cell carcinoma of the head and neck were analyzed by
      immunohistochemistry using antibodies specific for Bcl-xL, Bcl-2, and p53.
      Measures of clinical outcome, including disease specific survival and overall
      survival, were compared among the groups. RESULTS: The majority of the tumors
      demonstrated enhanced expression of either Bcl-2 or Bcl-xL compared with
      surrounding normal epithelium. Fifty-two percent of the tumors had up-regulated
      Bcl-xL, and 17% had up-regulated Bcl-2. There was no overlap between these
      groups. Expression of Bcl-2, but not Bcl-xL, was correlated with improved disease
      specific survival. Immunohistochemically detectable p53 expression (48% of
      tumors) was not found to correlate with expression of either Bcl-xL or Bcl-2 and,
      in this series, was not a predictor of clinical outcome. CONCLUSIONS: These
      results suggest that disruption of apoptotic control pathways is an important
      event in the evolution of squamous cell carcinoma of the head and neck. A common
      mechanism for this disruption involves overexpression of Bcl-xL, Patients whose
      tumors demonstrate Bcl-2 positivity, even with locoregionally advanced disease,
      appear to have a high likelihood of cure with aggressive combined modality
      therapy and may be treated successfully with less toxic therapy.

PMID- 9921990
TI  - Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in
      the search for unknown primary tumors.
AB  - BACKGROUND: Metastatic adenocarcinoma in the liver with an unidentified primary
      tumor site is a common clinical problem. Pathologists often are asked to identify
      the primary tumor site. The histologic picture itself usually is not helpful,
      because the histology may be similar in the metastases of tumors with different
      primary localizations. Immunohistochemistry can be helpful, but the previously
      recommended antibody panels are too complicated for everyday use. METHODS: A
      simple immunohistochemical algorithm with two monoclonal cytokeratin (CK)
      antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas
      metastatic to the liver. Sections of the liver metastases were stained
      automatically and evaluated as negative (no staining), focally positive, or
      diffusely positive. Statistical comparison of the staining results for a single
      antibody was calculated as an odds ratio. RESULTS: Thirty-six of 93 (39%)
      metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative
      (-) pattern was highly characteristic for colorectal localization of the primary
      tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern
      of the metastatic liver adenocarcinomas was highly suggestive of primary
      localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of
      the tumors originating in the stomach raised these values to 94% and 92%,
      respectively. The statistically calculated predicted probability of primary tumor
      site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the
      probability of a primary tumor being located in the pancreas or biliary tract was
      74,85%, if calculated for the whole study group. CONCLUSIONS: The tested simple
      algorithm proved to be useful in CK20 positive (+) cases, predicting a primary
      tumor localization in the colon, rectum, pancreas, or biliary tract with high
      accuracy. The CK20- group was too heterogeneous to be classified adequately by
      these two antibodies.

PMID- 9921991
TI  - Vascular endothelial growth factor in the sera and effusions of patients with
      malignant and nonmalignant disease.
AB  - BACKGROUND: Clinical data clearly indicate a correlation between tumor
      neovascularization, aggressiveness of tumor growth, and metastatic spread. One of
      the key factors capable of stimulating tumor angiogenesis is vascular endothelial
      growth factor (VEGF). Using an immunoassay for VEGF, we assessed the levels of
      soluble VEGF in the sera and effusions of patients with malignant and
      nonmalignant disease as well as in the sera of healthy controls. METHODS: Using a
      sandwich enzyme-linked immunoadsorbent assay, the concentration of VEGF was
      measured in serum specimens (n=445) and effusions (n=56) collected from a total
      of 212 patients with various types of cancer, 88 patients with nonmalignant
      disease, and 145 healthy individuals. RESULTS: Low and rather stable levels of
      VEGF were detected in the serum of healthy individuals (median, 294 pg/mL; range,
      30-1752 pg/mL; 95th percentile, 883 pg/mL). Compared with healthy individuals,
      serum levels in patients with acute infections were elevated (P=0.03), whereas
      patients with chronic cirrhosis had lower serum VEGF levels. Among patients with
      various types of neoplasia, VEGF serum levels in patients with ovarian or
      gastrointestinal carcinoma were significantly higher than in healthy individuals.
      Moreover, VEGF concentrations in sera from patients with metastatic disease were
      higher than in sera from patients with localized tumors. Maximum serum
      concentrations of VEGF (median, 1022 pg/mL; range, 349-7821 pg/mL) were found in
      patients with metastatic ovarian carcinoma. Median VEGF levels (and ranges) in
      malignant effusions were up to 10-fold higher than in matched serum samples: 5528
      pg/mL (468-49269 pg/mL) in ovarian carcinoma, 885 pg/mL (77-14,337 pg/mL) in
      breast carcinoma, and 813 pg/mL (372-18,331 pg/mL) in gastrointestinal carcinoma.
      In contrast, ascitic fluid from patients with cirrhosis contained only 303 pg/mL
      (median, range 116-676 pg/mL) of VEGF, corresponding to the low serum levels in
      this patient group. CONCLUSIONS: Depending on the tumor type, elevated levels of
      VEGF are detectable in the serum of only 0-20% of patients with localized cancer
      but in 11-65% of patients with metastatic cancer. Of cytology-proven malignant
      ascites or peritoneal exudates from various malignancies, 46-96% show VEGF levels
      above the upper limit (95th percentile, 676 pg/mL) of nonmalignant ascites.
      Maximum VEGF concentrations in malignant effusions indicate abundant local
      release of VEGF within the pleural or peritoneal cavity. These results suggest
      that VEGF might play an important role in tumor progression and the formation of
      malignant effusions. Further studies are warranted to determine the clinical
      value of soluble VEGF as a tumor marker, a prognostic factor, and a surrogate
      indicator of tumor angiogenesis.

PMID- 9921992
TI  - Expression of somatostatin receptors in peritumoral veins of human tumors.
AB  - BACKGROUND: The vascular system of the tumor bed plays an important function in
      tumor growth regulation. Recent studies have suggested that the vasoactive
      peptides somatostatin and substance P may have a potential role in the tumor bed
      of selected tumors. METHODS: In the current study, somatostatin receptors were
      evaluated with in vitro receptor autoradiography using 125I-[Tyr3]-octreotide in
      the peritumoral vessels of a large group of 215 primary human tumors and 25
      metastases of various tumor origin, with particular emphasis on receptor
      incidence, distribution, homogeneity, and density. RESULTS: High affinity
      somatostatin receptors were found in the peritumoral veins of 22 of 22 gastric
      carcinomas, 25 of 39 breast carcinomas, 15 of 20 renal cell carcinomas, 14 of 27
      prostate carcinomas, 4 of 10 endometrial carcinomas, 4 of 11 pancreatic
      adenocarcinomas, 4 of 13 nonsmall cell lung carcinomas, as well as in 3 of 4
      parathyroid adenomas, 3 of 3 medullary thyroid carcinomas, 3 of 23
      gastroenteropancreatic tumors, 14 of 25 soft tissue tumors, 3 of 5 melanomas but
      in none (0 of 13) of the ovarian carcinomas studied. In addition, somatostatin
      receptors were identified in veins surrounding lymph node, bone, and lung
      metastases of various tumor types. In all investigated tissues, receptors could
      not be identified in arteries. There was a considerable variability in the
      relative number of veins expressing somatostatin receptors and in the receptor
      density levels. Evidence of an overexpression of somatostatin receptors could be
      established in the peritumoral veins of gastric carcinoma when compared with the
      receptor expression in normal gastric vessels. CONCLUSIONS: The expression of
      somatostatin receptors in peritumoral veins appears to be a general, tumor
      related, but highly variable phenomenon. Although their pathophysiologic role is
      unclear, these receptors may be considered as novel targets for cancer diagnosis
      and therapy with somatostatin analogs.

PMID- 9921993
TI  - Secondary lymph node involvement from primary cutaneous large B-cell lymphoma of
      the leg: sentinel lymph nodectomy as a new strategy for staging circumscribed
      cutaneous lymphomas.
AB  - BACKGROUND: Primary cutaneous large B-cell lymphoma of the leg (LBCLL) is a
      recently defined type of non-Hodgkin's lymphoma. It forms a separate category in
      the new classification of primary cutaneous lymphomas elaborated by the European
      Organization for Research and Treatment of Cancer. It is associated with a less
      favorable prognosis than the most frequently occurring types of primary cutaneous
      B-cell lymphoma. METHODS: The authors present four patients with the typical
      clinicopathologic constellation of LBCLL. Three of them died during the years
      1993-1996. The authors reviewed their courses. The fourth patient was staged by
      sentinel lymph nodectomy (SLNE), i.e., the selective surgical removal and
      histologic examination of the first draining lymph node associated with the
      cutaneous tumor. RESULTS: The courses of the three previous patients were
      characterized by secondary involvement of regional lymph nodes followed by
      systemic dissemination of the lymphoma in a third step. Although the conventional
      staging of the fourth patient had been negative for any extracutaneous lymphoma
      manifestation, the SLNE revealed initial regional lymph node involvement, which
      had decisive implications for the choice of therapy. CONCLUSIONS: SLNE may gain a
      prominent role in the staging of circumscribed cutaneous lymphomas, in addition
      to its already established position in melanoma management. Further positive
      effects of SLNE are 1) better distinction of primary cutaneous lymphomas with
      secondary lymph node involvement from primary lymph node lymphomas with skin
      manifestation, and 2) better insight into the biology of different primary
      cutaneous lymphoma types.

PMID- 9921994
TI  - The changing survival of patients with mycosis fungoides: a population-based
      assessment of trends in the United States.
AB  - BACKGROUND: The authors sought to evaluate trends in survival among a population
      based group of patients with mycosis fungoides, in response to informal evidence
      of improved prognosis and concerns about the influence of detection bias on
      incidence data. METHODS: Data used in this study were drawn from the
      Surveillance, Epidemiology, and End Results Program of the National Cancer
      Institute, which includes 9 population-based cancer registries. Together, these
      registries cover approximately 10% of the U.S. population and have tracked the
      survival of all mycosis fungoides patients who were registered during the years
      1973-1992. Data included follow-up through 1994. RESULTS: There was a total of
      over 10,000 person-years of follow-up for the 1633 patients studied. Relative
      survival changed little after 11 years, at which point it was 66%. Advanced age
      and black race were associated with poorer survival. The prognoses of Asian and
      Hispanic patients were slightly but not significantly worse than those of whites,
      and there were no significant geographic differences related to prognosis. The
      survival of married women was superior to that of other gender and marital-status
      groups. Prognosis did improve substantially over the 20-year period of study.
      CONCLUSIONS: Mycosis fungoides is usually not a fatal disease, although the
      mortality risk is substantial. The authors quantified various prognostic factors
      and documented an improved prognosis over the 20-year period of study. The data
      from this study raise concern about possible detection bias in incidence data.
      These data are also consistent with the concept that beyond 11 years after
      diagnosis, this disorder has relatively little impact on the risk of death.

PMID- 9921995
TI  - Outpatient therapy with oral ofloxacin for patients with low risk neutropenia and
      fever: a prospective, randomized clinical trial.
AB  - BACKGROUND: Hospitalization and treatment with broad-spectrum intravenous
      antibiotics is the standard care for patients with neutropenia and fever. This
      randomized clinical trial evaluated the feasibility and efficacy of ambulatory
      care with oral ofloxacin for patients with low risk, chemotherapy-induced
      neutropenia and fever. METHODS: Patients with solid tumors who were treated with
      conventional dose chemotherapy, presented with fever (axillary temperature >38
      degrees C on 2 occasions or >38.5 degrees C on a single occasion) and neutropenia
      (absolute neutrophil count, <500 cells/microL), and met low risk criteria were
      eligible for this study. They were randomized either to hospitalization and
      treatment with broad-spectrum intravenous antibiotics, which consisted of a
      combination of cefazidime and amikacin, or to outpatient treatment with oral
      ofloxacin. The definitions of fever of unknown origin, clinical and microbiologic
      infection, success, success with modification, and failure were the usual ones
      for this type of study. RESULTS: One hundred episodes were randomized, and 95
      were evaluable (47 were randomized to ceftazidime/amikacin and 48 to ofloxacin).
      Baseline characteristics, as well as the proportion of patients with
      microbiologic and clinical infections, were similar in the two groups. In 91% of
      episodes in the inpatient group and 89% in the ofloxacin group, patients
      recovered uneventfully (P=1; 95% CI for the difference, -0.09 to 0.13), with 2
      and 5 patients requiring modification of the antibiotics, respectively. Eight
      percent of episodes in the control group and 10.4% in the experimental group
      resulted in treatment failure. Eight patients (16%) in the outpatient group
      experienced failure with ambulatory care and were admitted to the hospital.
      CONCLUSIONS: Outpatient oral antibiotic therapy with oral ofloxacin for patients
      with low risk neutropenia and fever is safe and similar in efficacy to
      hospitalization and treatment with broad-spectrum parenteral antibiotics.

PMID- 9921996
TI  - Gastrointestinal autonomic nerve tumors in the pediatric population: a report of
      four cases and a review of the literature.
AB  - BACKGROUND: Gastrointestinal autonomic nerve tumors (GANTs) are a subpopulation
      of gastrointestinal stromal tumors (GISTs) that are characterized by
      ultrastructural features resembling enteric autonomic nerve cells, without
      epithelial, Schwannian, or smooth muscle differentiation. Delineation of the
      clinicopathologic features of GANT in the pediatric population is lacking.
      METHODS: The clinicopathologic and outcome data for four pediatric patients with
      GANT are presented. The data from these patients and four previously reported
      pediatric patients are summarized and compared with data for GANT in adults.
      RESULTS: All four cases occurred in females at a mean age of 12.5 years. The
      primary tumor site was the stomach in all cases, and the mean tumor size was 6.3
      cm. Immunocytochemical and ultrastructural examination were essential in
      distinguishing GANT from GIST in all cases by identifying features of neural
      origin (neuron specific enolase in all four cases, NFP in three cases, S-100 in
      two cases, dense core neurosecretory granules in all four cases, and neuritelike
      processes in all four cases), while failing to identify features of myogenic
      origin (no desmin, smooth muscle actin, myofilaments, or dense bodies were found
      in any of the cases). Primary treatment was surgical, with chemotherapy
      administered to 1 patient at the time of recurrence. All patients are alive after
      a mean follow-up of 60 months (range, 8 months to 9 years). CONCLUSIONS:
      Similarities of pediatric GANT to GANT in adults include the need for a high
      index of suspicion for diagnosis; comparable histopathologic,
      immunohistochemical, and ultrastructural features; and surgery as the primary
      therapy. Distinguishing features in children may be a prevalence among females in
      the second decade, a predominance of smaller gastric tumors, and a positive
      prognostic value of younger age.

PMID- 9921997
TI  - Membrane-type matrix metalloproteinase-1 expression and activation of gelatinase
      A as prognostic markers in advanced pediatric neuroblastoma.
AB  - BACKGROUND: Recently a novel membrane-type matrix metalloproteinase-1 (MT-MMP-1)
      was discovered to be a specific activator of progelatinase A, and was correlated
      with tumor invasion. To the authors' knowledge, no information regarding the
      expression of MT-MMP-1 has been reported in childhood malignancies. In this
      study, the authors attempted to elucidate the specific mechanisms that underlay
      the invasive behavior of neuroblastoma (NB) cells with respect to the expression
      of MT-MMP-1 and its determined prognostic value, especially in pediatric patients
      with advanced Evans' Stage IV NB. METHODS: Thirty specimens from surgically
      excised NB (mainly Stage IV) were collected retrospectively. The total levels of
      progelatinase A (68 kilodaltons [kD]) and its activated form (62 kD) in the tumor
      lysates were quantified by gelatin zymography. The expression of MT-MMP-1 was
      estimated by immunostaining with a monoclonal antibody (113-5B7). RESULTS:
      Progelatinase A and the activated form were detected in each of the 30 specimens.
      The gelatinase A activation ratio, 62 kD/(62 kD + 68 kD), strongly correlated
      with the high levels of MT-MMP-1 expression found in specimens of advanced tumor
      stage. In the patients with advanced Stage IV NB, the activation ratio was
      strongly associated with unfavorable clinical outcome; the 5-year survival was
      88.9% in the patients with a low activation ratio (< or = 26%) versus only 21.2%
      in the patients with a high activation ratio (>26%). CONCLUSIONS: Gelatinase A
      activation correlates with high expression of MT-MMP-1 on NB cells and is
      associated strongly with advanced stage and poor clinical outcome. These results
      are consistent with the notion that MT-MMP-1 expression is an important
      prognostic determinant of the biologic behavior of NB.

PMID- 9921998
TI  - Bone marrow staging of patients with non-Hodgkin's lymphoma: is flow cytometry a
      useful test?

PMID- 9921999
TI  - Long term follow-up and late complications of 2-chlorodeoxyadenosine in
      previously treated, advanced, indolent non-Hodgkin's lymphoma.

PMID- 9922000
TI  - Lymph node harvest reporting in patients with carcinoma of the large bowel: a
      French population-based study.

PMID- 9922002
TI  - Utilization of polymerase chain reaction technology in the detection of solid
      tumors.

PMID- 9922001
TI  - Telomerase activity in precancerous hepatic nodules.

PMID- 9922003
TI  - The use of epithelial membrane antigen and silver-stained nucleolar organizer
      regions testing in the differential diagnosis of mesothelioma from benign
      reactive mesothelioses.

PMID- 9922004
TI  - Stereotactic radiosurgery for brain metastasis from renal cell carcinoma.

PMID- 9922005
TI  - Why hereditary nonpolyposis colorectal carcinoma patients appear to have better
      survival than patients with sporadic colorectal carcinoma.

PMID- 9922006
TI  - Pretreatment surgical staging of patients with cervical carcinoma: the case for
      lymph node debulking.

PMID- 9922007
TI  - Behcet's disease and complex aphthosis.
AB  - Behcet's disease is a complex multisystem disease diagnosed by means of clinical
      criteria. Clinical features include oral and genital aphthae, pustular vasculitic
      cutaneous lesions, and ocular, gastrointestinal, and vascular manifestations. We
      believe that complex aphthosis, characterized by oral or oral and genital ulcers,
      may be a forme fruste of Behcet's disease. Although the pathogenesis of both
      Behcet's disease and complex aphthosis remain unknown, immune factors, infectious
      agents, and effector mechanisms are implicated. Treatment is based on the
      severity of systemic involvement and includes topical therapies as well as
      colchicine, dapsone, thalidomide, and immunosuppressive agents.

PMID- 9922008
TI  - Nevus depigmentosus: clinical features and histopathologic characteristics in 67
      patients.
AB  - BACKGROUND: Nevus depigmentosus is defined as a congenital nonprogressive
      hypopigmented macule or patch that is stable in its relative size and
      distribution throughout life. The pathogenesis and histopathologic
      characteristics of nevus depigmentosus is not yet fully established. OBJECTIVE:
      The purpose of this study was to investigate the clinical and histopathologic
      characteristics of nevus depigmentosus as well as its pathogenesis. METHODS: A
      clinical survey was done with 67 patients diagnosed as having nevus
      depigmentosus. Two skin biopsy specimens each were taken from 18 patients: one
      from the central part of the depigmented lesion and another from the border of
      the lesion, including perilesional normal skin. The sections were stained with
      hematoxylin-eosin, Fontana-Masson, and S-100 protein. Ultrastructural evaluation
      was also done to detect changes of the melanocytes. RESULTS: The lesions were
      mostly present before 3 years of age (92.5%), but some lesions also appeared
      later in childhood (7.5%). The back and buttocks were the most commonly affected
      sites, followed by the chest and the abdomen, the face, the neck, and the arms.
      Forty patients (59.7%) had the isolated type of nevus depigmentosus and 27
      patients (40.3%) had the segmental type. Histopathologic studies showed that the
      staining ability of Fontana-Masson in nevus depigmentosus lesions decreased
      compared with perilesional normal skin. However, there were no changes in the
      numbers of melanocytes identified as S-100-positive cells in the basal layer.
      Electronmicroscopic studies revealed a great reduction in the number of
      melanosomes in melanocytes and some membrane-bound aggregated melanosomes were
      observed in keratinocytes. CONCLUSION: The results of this study support the
      hypothesis that nevus depigmentosus is caused by the functional defects of
      melanocytes and the morphologic abnormalities of melanosomes.

PMID- 9922009
TI  - Skin cancer in Australian heart transplant recipients.
AB  - BACKGROUND: Cutaneous malignancy is a major cause of morbidity in organ
      transplant recipients. OBJECTIVE: Our purpose was to report on skin cancer in
      Australian heart transplant recipients with analysis of HLA factors. METHODS: We
      reviewed histologically proven skin cancers in the first 455 patients undergoing
      organ transplantation in Sydney, Australia. RESULTS: The cumulative incidence of
      skin cancer was 31% at 5 years and 43% at 10 years with a squamous cell
      carcinoma/basal cell carcinoma ratio of 3:1. Caucasian origin, increasing age at
      transplantation, and duration of follow-up were significantly associated with
      skin cancer. Skin cancer accounted for 27% of 41 deaths occurring after the
      fourth year. Recipient HLA-DR homozygosity was associated with skin cancer
      overall, whereas HLA-DR7 was a protective factor in skin cancer overall, squamous
      cell carcinoma, and Bowen's disease. HLA-A1 and HLA-A11 were significant
      protective factors in Bowen's disease. CONCLUSION: Skin cancer is a major cause
      of morbidity and long-term mortality in heart transplant patients.

PMID- 9922010
TI  - Update on the incidence and mortality from melanoma in the United States.
AB  - BACKGROUND: Increases in the incidence of malignant melanoma have been among the
      largest of all cancers in the United States. OBJECTIVE: We report updated trends
      in melanoma rates among the US white population. METHODS: Incidence and mortality
      rates were calculated for 1973 to 1994. Trends were examined with stratification
      by state, age, and sex, and by anatomic site, stage, and melanoma thickness at
      diagnosis. RESULTS: Melanoma incidence and mortality rates increased dramatically
      from 1973 to 1994, rising 120.5% and 38.9%, respectively. In recent years,
      however, rates for most age-sex groups appeared to stabilize or even decline.
      Male patients continued to have higher incidence and mortality rates than female
      patients, but for both male and female patients the largest increases by site
      were for the trunk. A large proportion of melanomas were detected in the local
      stage and with a thickness less than 0.75 mm. CONCLUSION: Prevention of sun
      exposure is recommended to reverse the high incidence rates of melanoma.

PMID- 9922011
TI  - Destructive procedures are the standard of care for treatment of actinic
      keratoses.
AB  - BACKGROUND: Actinic keratoses are premalignant lesions resulting from exposure to
      carcinogens. Recently, some Medicare carriers have limited reimbursement for
      destruction of actinic keratoses to those lesions unresponsive to topical 5
      fluorouracil treatment. OBJECTIVE: Our purpose was to determine whether this
      policy meets the community standard of care for treatment of actinic keratoses.
      METHODS: Data from the 1993 and 1994 National Ambulatory Medical Care Survey were
      used to determine the frequencies at which different treatments are used for
      actinic keratoses. These were compared with the frequencies at which procedures
      and medical therapies are used to treat control conditions (warts, psoriasis,
      acne, and dermatitis) to determine whether procedures are done because they are
      available or out of medical necessity. RESULTS: Procedures were performed during
      78% of visits for actinic keratoses. 5-Fluorouracil was used at 3.6% of visits,
      and at 39% of these visits a procedure was also performed. There were no
      observations of use of 5-fluorouracil alone at a first visit for actinic
      keratosis. Procedures were less likely to be performed at visits for warts,
      psoriasis, acne, or dermatitis, which indicates that reimbursable procedures are
      performed not simply because they are available. CONCLUSION: Procedures are
      performed to destroy actinic keratoses out of medical need. Medicare policies
      mandating initial use of 5-fluorouracil as initial treatment of actinic keratoses
      do not represent the community standard of care for treatment of these lesions.

PMID- 9922013
TI  - Clinical and dermatoscopic criteria for the preoperative evaluation of cutaneous
      melanoma thickness.
AB  - BACKGROUND: Melanoma thickness measured according to the Breslow method is used
      to determine surgical margin and in patient selection for sentinel node biopsy.
      Previous studies did not confirm the reliability of melanoma palpability for
      clinical prediction of tumor thickness. Recently we reported the usefulness of
      epiluminescence microscopy (dermatoscopy) for in vivo detection of the phases of
      melanoma progression, as well as tumor depth. OBJECTIVE: Our purpose was to
      determine whether the combination of clinical and dermatoscopic criteria could
      increase the accuracy in preoperative evaluation of melanoma thickness with
      respect to the clinical elevation and dermatoscopic assessments considered
      separately. METHODS: In a blind retrospective study, 122 cutaneous melanomas were
      studied to evaluate the presence of several clinical and dermatoscopic criteria
      and their relation with the histologic thickness. An algorithm of combined
      criteria was constructed and statistically assessed. RESULTS: Combinations of
      palpability, diameter of more than 15 mm, pigment network, gray-blue areas, and
      atypical vascular pattern allowed correct prediction of thickness in 89% of
      melanomas when categorized in two groups of less than 0.76 mm and more than 0.75
      mm thickness, compared with 75% using palpability, and 80% using dermatoscopic
      criteria. Lower values were obtained in the further subdivision of melanomas into
      groups of 0.76 to 1.5 mm and more than 1.5 mm thickness. CONCLUSION: The
      combination of clinical and dermatoscopic criteria is a more precise guide for
      the preoperative evaluation of melanoma thickness than either is alone. However,
      further studies are needed to verify its applicability in establishing the
      surgical approach to cutaneous melanoma.

PMID- 9922012
TI  - Alterations in HIV expression in AIDS patients with psoriasis or pruritus treated
      with phototherapy.
AB  - BACKGROUND: Ultraviolet light (UVL) upregulates HIV transcription in vitro and in
      transgenic mice. AIDS-associated psoriasis and pruritus respond to phototherapy.
      OBJECTIVE: Our goal was to determine the effect of phototherapy on viral load and
      immunologic parameters in HIV-positive patients. METHODS: T cell subsets, p24,
      plasma cytokines, serum or plasma HIV-RNA, dosage, and antivirals were assessed
      in HIV-positive patients and negative controls receiving 6 weeks of phototherapy
      with UVB and in untreated controls. RESULTS: Phototherapy improved skin
      conditions without significantly affecting T cell numbers. Plasma p24 increased 2
      fold (P = .055) and HIV-RNA levels 4-fold (P = .022) 6 weeks from baseline in
      patients who entered the trial before March 1995. Later patients who were mostly
      receiving combination antiviral therapy showed a 4-fold reduction in serum HIV
      RNA (P = .012) at 2 weeks. The effect of UVB on viral load at 6 weeks was
      dependent on the baseline level (P = .006). IL-10 increased and was inversely
      related to HIV-RNA levels (P = .0267). CONCLUSION: Phototherapy is associated
      with HIV load alterations, depending on patients' initial HIV-RNA, antiviral
      therapy, skin type, and UVL dosage.

PMID- 9922014
TI  - Long-term antibiotic therapy for balanitis xerotica obliterans.
AB  - In an open uncontrolled study of 3 patients with balanitis xerotica obliterans we
      have observed significant improvement after long-term systemic antibiotic
      therapy. Two of the patients noticed softening of the skin as well as
      disappearance of pruritus, tenderness, and inflammatory changes within 3 weeks of
      receiving oral and intramuscular penicillin. The third patient experienced the
      same degree of improvement after a regimen of dirithromycin, 500 mg/day. Stopping
      the antiobiotic for 1 month resulted in relapse, with improvement again on
      resumption.

PMID- 9922015
TI  - Long-term results of isotretinoin in the treatment of 68 patients with
      hidradenitis suppurativa.
AB  - BACKGROUND: Oral isotretinoin has been used to treat mild to severe hidradenitis
      suppurativa (HS). OBJECTIVE: We reviewed the results of low-dose isotretinoin for
      4 to 6 months in the treatment of 68 patients with HS. METHODS: This is a
      retrospective study. Data are presented in terms of response rate, long-term
      follow-up, and the relation between response rate and severity. RESULTS: In 16
      patients (23.5%), the condition completely cleared during initial therapy and 11
      patients (16.2%) maintained their improvement during the follow-up period.
      Treatment was more successful in the milder forms of HS. CONCLUSION: Monotherapy
      with isotretinoin for patients with HS usually has a limited therapeutic effect.

PMID- 9922016
TI  - Prophylactic antibiotics in patients undergoing laser resurfacing of the skin.
AB  - BACKGROUND: Carbon dioxide (CO2) laser resurfacing produces a superficial second
      degree burn that needs to be protected from bacterial and fungal infections.
      OBJECTIVE: We investigated the effects of various systemic and topical
      antimicrobial regimens. METHODS: Four different regimens using oral
      ciprofloxacin, topical antibiotics (intranasal mupirocin ointment and otic
      solution), oral ketoconazole, and oral fluconazole were tested in four time
      periods. The frequency and types of the infections with various regimens was
      compared. RESULTS: The study included 356 sequential patients who underwent
      facial CO2 laser resurfacing. Infections occurred in 27 patients (7.6%). Without
      antibiotic prophylaxis, 8.2% of patients had bacterial infections from days 3 to
      12 after the procedure (average, day 5). With prophylactic ciprofloxacin only,
      4.3% of patients had bacterial infections; these occurred almost exclusively
      after ciprofloxacin was discontinued. For 7 months, patients were randomly
      assigned to either receive or not receive mupirocin intranasally. All
      Staphylococcus aureus infections that occurred were seen in patients who had used
      intranasal mupirocin. Yeast infections were seen in 6 patients (1.7%), but mostly
      occurred more than 10 days after the procedure. Yeast infections were of
      approximately equal occurrence in the ciprofloxacin group (2.2%) and in the non
      ciprofloxacin group (1.8%). No yeast infections occurred in patients who had
      undergone antifungal prophylaxis. CONCLUSION: Post-CO2 resurfacing infections are
      not rare but can appear subtly and might only be noticeable in the second
      postoperative week. Prophylactic intranasal mupirocin is ineffective, but
      ciprofloxacin is effective in preventing infection with both gram-positive and
      gram-negative bacteria. Oral ketoconazole and fluconazole are effective in
      preventing yeast infections.

PMID- 9922017
TI  - Microfine zinc oxide (Z-cote) as a photostable UVA/UVB sunblock agent.
AB  - BACKGROUND: Microfine zinc oxide (Z-Cote) is used as a transparent broad-spectrum
      sunblock to attenuate UV radiation (UVR), including UVA I (340-400 nm).
      OBJECTIVE: Our purpose was to assess the suitability of microfine zinc oxide as a
      broad-spectrum photoprotective agent by examining those properties generally
      considered important in sunscreens: attenuation spectrum, sun protection factor
      (SPF) contribution, photostability, and photoreactivity. METHODS: Attenuation
      spectrum was assessed by means of standard spectrophotometric methods. SPF
      contribution was evaluated according to Food and Drug Administration standards.
      Photostability was measured in vitro by assessing SPF before and after various
      doses of UVR. Photoreactivity was evaluated by subjecting a microfine zinc
      oxide/organic sunscreen formulation to escalating doses of UVR and determining
      the percentage of organic sunscreen remaining. RESULTS: Microfine zinc oxide
      attenuates throughout the UVR spectrum, including UVA I. It is photostable and
      does not react with organic sunscreens under irradiation. CONCLUSION: Microfine
      zinc oxide is an effective and safe sunblock that provides broad-spectrum UV
      protection, including protection from long-wavelength UVA.

PMID- 9922018
TI  - Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus.
AB  - BACKGROUND: IgA pemphigus of the subcorneal pustular dermatosis (SPD) type is
      characterized by subcorneal acantholysis and by an abundance of neutrophils,
      making colchicine a reasonable pharmacologic option for treatment. OBJECTIVE: We
      attempted to determine the efficacy of colchicine in the treatment of SPD-type
      IgA pemphigus. METHODS: Two patients with SPD-type IgA pemphigus were treated
      with colchicine 1.5 mg/day as monotherapy. RESULTS: A sustained clinical response
      was achieved within 2 to 3 weeks of therapy. Relapses were noted each time
      colchicine was stopped. CONCLUSION: Colchicine should be considered in the
      treatment of SPD-type IgA pemphigus.

PMID- 9922019
TI  - The principle of a three-staged operation in the surgery of acne scars.
AB  - BACKGROUND: Acne scars cannot be effectively corrected by a single treatment
      modality because of their widely varied depth and width. OBJECTIVE: We assessed
      the effectiveness of staged combinations of several surgical modalities in the
      treatment of acne scars. METHODS: Focal chemical peeling, carbon dioxide (CO2)
      laser, scar excision, punch grafting, and dermabrasion were used. Initially,
      focal chemical peeling was performed on all patients and then CO2 laser, scar
      excision, and punch grafts were used for deep scars. Finally, dermabrasion was
      done for the remaining scars. RESULTS: Seventy-five percent of patients showed
      excellent or good results. The degree of improvement increased as the follow-up
      periods and number of focal chemical peeling procedures increased and as the 3
      staged operation progressed. CONCLUSION: A 3-staged operation is effective in the
      treatment of patients with various types of acne scars.

PMID- 9922020
TI  - Mohs micrographic surgery for the treatment of in situ nail apparatus melanoma: a
      case report.
AB  - Nail apparatus melanoma (or subungual melanoma) is rare and accounts for only
      1.4% of all cutaneous melanomas in the United Kingdom. We report the use of fixed
      tissue Mohs micrographic surgery to treat a biopsy-proven Clark level I in situ
      nail apparatus melanoma, presenting with diffuse longitudinal melanonychia.

PMID- 9922021
TI  - Adverse reactions after cosmetic lip augmentation with permanent biologically
      inert implant materials.
AB  - Augmentation of lips is a common aesthetic procedure that is mostly performed
      with alloplastic materials or autologous tissue. Various alloplastic injectable
      implants have been developed for soft tissue augmentation without surgery. Most
      biologic materials are resorbed within a few months, fluid silicone may migrate,
      and autologous fat is not ideal for fine contouring of the lips. The search for a
      biocompatible, permanent, nontoxic, and biologically inert filler material led to
      the development of some new materials for subdermal or intradermal implantation.
      Recently Bioplastique, Artecoll, and Gore-Tex have been well established and
      recommended by many authors. Although these materials meet most of the
      characteristics that constitute an ideal injectable prosthetic material, we
      describe 3 examples of adverse reactions after their implantation into lips.

PMID- 9922022
TI  - Surgical pearl: the modified buried dermal suture.

PMID- 9922023
TI  - Interferon alfa-2b-induced Meyerson's nevi in a patient with dysplastic nevus
      syndrome.

PMID- 9922024
TI  - The midline part: an important physical clue to the clinical diagnosis of
      androgenetic alopecia in women.

PMID- 9922025
TI  - Severe urticarial reaction to diphenylcyclopropenone therapy for alopecia areata.

PMID- 9922026
TI  - Physician, heed thy shelf.

PMID- 9922027
TI  - Effects of altitude and latitude on ambient UVB radiation.

PMID- 9922028
TI  - A novel chemotherapeutic regimen (interferon alfa, zidovudine, and etretinate)
      for adult T-cell lymphoma resulting in rapid tumor destruction.

PMID- 9922029
TI  - Intracellular interleukin-4 profiles during high-dose intravenous immunoglobulin
      treatment of therapy-resistant atopic dermatitis.

PMID- 9922030
TI  - Curved nail of the fourth toe.

PMID- 9922031
TI  - The affliction of Job: poisoned!
AB  - The story of Job has been an inspiration for centuries to those familiar with the
      story. It has also been a source of curiosity as to what affliction he suffered.
      A critical reappraisal of the clinical manifestations of his illness support the
      contention that he was a victim of poisoning. There is historical evidence to
      support that the poison was available in his time and already in use for
      poisoning. Finally, there is even documentation in the story of Job as to the
      identity of his poisoner.

PMID- 9922032
TI  - Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus.

PMID- 9922033
TI  - Pressure ulcers.

PMID- 9922034
TI  - From other ghosts of the past: acne lesion counting.

PMID- 9922036
TI  - The role of bisphosphonates for the treatment of bone disease in multiple
      myeloma.
AB  - Palliative therapy is often a major objective for clinicians while treating
      advanced cancer. This is particularly true in multiple myeloma (MM), where bone
      involvement markedly influences the quality of life of patients. Bisphosphonates
      (BP) are a new class of drugs regulating bone turnover, which exert their
      activity mainly by inhibiting osteoclast bone resorption. Three BP (etidronate,
      ETD; clodronate, CDN; pamidronate, PMD) have so far been investigated in the
      clinical setting for treating bone disease in patients with MM. The results of
      these trials, including our own experience, are reviewed here. Although all three
      BP were effective in lowering hypercalcemia of MM patients, PMD, a second
      generation BP, clearly had the most substantial long term clinical benefits
      regarding bony complications, pain and quality of life. CDN also showed some
      activity in reducing the development of new lytic lesions, while no significant
      beneficial effect was seen in patients using ETD. Interestingly, some studies
      have reported an improved survival in subsets of MM patients receiving BP and
      this is in agreement with recent evidence of possible direct anti-neoplastic
      activities of these drugs mediated through reduction of IL-6 production and
      stimulation of neoplastic cell apoptosis.

PMID- 9922035
TI  - Relapsed acute promyelocytic leukemia previously treated with all-trans retinoic
      acid: clinical experience with a new synthetic retinoid, Am-80.
AB  - All-trans retinoic acid (ATRA), a potent differentiating drug for acute
      promyelocytic leukemia (APL), induces a high incidence of complete remission (CR)
      in patients with APL and is now established as a first-line therapy. However,
      ATRA resistance has become a clinical problem. Patients who relapsed after ATRA
      induced CR have had difficulty in obtaining a second CR with ATRA therapy.
      Although several mechanisms have been postulated, treatment strategies to
      overcome resistance have not been established. We used a new synthetic retinoid,
      Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80
      was several times more potent than ATRA in inducing differentiation in vitro. At
      a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between
      days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro
      response to Am-80. Adverse effects included retinoic acid syndrome (n = 1),
      hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8),
      hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active
      in APL after relapse from ATRA-induced CR. Further clinical trials are needed to
      establish strategies to overcome ATRA resistance.

PMID- 9922037
TI  - Hepatitis C virus infection, mixed cryoglobulinemia, and non-Hodgkin's lymphoma:
      an emerging picture.
AB  - Hepatitis C virus (HCV) is a single-stranded RNA agent which expresses its
      genetic informations in the form of a single, large polyprotein encoded by an
      open reading frame (ORF) that extends through most of its genomic RNA.
      Proteolytic cleavage of the ORF product is essential for the virogenesis and the
      production of viral progeny. HCV is responsible for chronic liver disease,
      cirrhosis and possibly hepatocellular carcinoma. Viral persistence is considered
      the greatest problem in the management of HCV infection. It may result from
      several mechanisms, two of which are established. In the first, the high rate of
      genetic variations during viral replication results in the production of mutants
      capable of escaping the immune attack. In the second, the virus infects cells of
      the immune system itself, which represent a privileged site that cannot be
      reached by virus-specific T cell response. Involvement of lymphoid cells in the
      early stages of HCV infection may provide insight into the pathobiologic patterns
      of extrahepatic dissemination (lymph nodes, major salivary glands, kidneys, blood
      vessels). Dissemination of HCV-infected lymphoid cells throughout the organism is
      likely to maintain a mobile and extensive reservoir of the virus. In this
      respect, extrahepatic sites may act as a source of continuous reinfection of
      hepatocytes. Studies of intrahepatic B lymphocytes indicate that they are
      infected with HCV, clonally expanded and activated to secrete IgM molecules with
      rheumatoid factor activity. This strongly suggests that HCV directly stimulates B
      cell expansion, which may result in an indolent stage of lymphoproliferation
      (i.e., mixed cryoglobulinemia) or in frank B cell non-Hodgkin's lymphoma (NHL).
      The frequency of NHL, however, is much lower than that of HCV infection,
      suggesting that HCV alone is not able to induce tumors and that cellular events,
      in addition to the presence of virus and virus-encoded products, are necessary in
      order to obtain a malignant B cell phenotype. The demonstration of HCV productive
      infection in bone marrow-recruited and circulating pluripotent hematopoietic
      CD34+ stem cells indicates that HCV replication occurs in the early
      differentiation stages of hematopoietic progenitors. These are stable cell
      populations and are likely to represent the initial site of infection and a
      continuous source of virus production.

PMID- 9922038
TI  - On the role and significance of Fas (Apo-1/CD95) ligand (FasL) expression in
      immune privileged tissues and cancer cells using multiple myeloma as a model.
AB  - Our knowledge in immunology has been dramatically increased by several excellent
      investigations elucidating the role of the Fas (Apo-1/CD95) receptor/ligand
      (FasL) system in complex immunological processes such as the acquisition of self
      tolerance in T cells, progression of autoimmunity, clonal deletion of activated T
      cells, B-cell regulation and the establishment of "immune privileged" sites such
      as testis or retina. In addition to these regulatory immunological activities,
      Fas/FasL interaction was also shown to participate in active defense mechanisms
      of the host against infected or transformed cells thereby inducing apoptosis in
      target cells. However, the same mechanism seems also to be part of an escape
      strategy utilized by tumor cells in various neoplastic malignancies of both
      hematopoetic as also non-hematopoetic origin. We ourselves were able to
      demonstrate that neoplastic plasma cell lines, as well as native malignant
      myeloma cells constitutively express FasL mRNA and protein. The FasL molecule is
      functionally active and able to induce programmed cell death in Fas sensitive
      target T cells in vitro. These target T cells were protected from programmed cell
      death by preincubation of T cells with a Fas-blocking monoclonal antibody (mAb)
      or of myeloma cells with a FasL-neutralizing mAb. respectively. Furthermore,
      overexpression of the caspase inhibitor, cowpoxvirus protein CrmA, also protected
      target T cells from being killed by myeloma cells, identifying Fas/FasL mediated
      signaling as the effector pathway utilized by malignant plasma cells. Our
      observations strongly suggest the engagement of Fas/FasL interaction in the
      escape strategy of this malignancy. The molecular basis of this evasive mechanism
      differs in essential respects from those described in melanoma, lung cancer,
      hepatocellular carcinoma, or astrocytoma, since downregulation of Fas or
      instrinsic insensitivity towards Fas-mediated signaling were not prerequisites
      for the occurrence of this phenomenon in Fas-sensitive multiple myeloma cell
      lines. However, myeloma cell lines resisted cocultivation with FasL-expressing
      target T cells in vitro. The aim of this review is to discuss the role of
      Fas/FasL interaction in the establishment of malignant disease, in the light of
      our findings on myeloma cells and also by drawing upon similar observations of
      other investigators on different kinds of tumor cells and cell lines and further
      to consider its possible relevance in formulating novel approaches to cancer
      therapy.

PMID- 9922039
TI  - The role of von Willebrand factor in the hemostatic defect of acute promyelocytic
      leukemia.
AB  - Bleeding complications are often associated with acute promyelocytic leukemia
      (APL) they occur frequently at the onset of APL and become more serious during
      chemotherapy. The increased bleeding tendency of APL is caused by a massive
      proteolytic state, triggered by procoagulant substances, plasminogen activators
      and proteinases released into the circulation from leukemic cells. The
      introduction of all-trans-retinoic acid (ATRA) into the treatment of APL has
      reduced bleeding complications. However the mechanisms of the hemostatic defects
      in patients with APL and their modifications during ATRA with or without
      chemotherapy are still incompletely understood. Attempts at characterizing and
      monitoring these hemostatic abnormalities have been made by using several
      laboratory parameters. Among them we have studied the structural modifications of
      von Willebrand Factor (vWF). In APL, plasma vWF is massively degraded, with
      specific fragments produced by the action of plasmin and elastase. After ATRA
      therapy, proteolysis diminishes progressively in parallel with the improvement of
      other hemostatic measurements. We conclude that abnormalities of vWF structure
      and function might adversely affect hemostasis in APL and that their improvement
      after ATRA administration might explain in part the effectiveness of this drug in
      reducing hemorrhagic complications.

PMID- 9922040
TI  - Clinical importance of speed of response to therapy in childhood lymphoblastic
      leukaemia.
AB  - Speed of response to therapy predicts outcome in childhood lymphoblastic
      leukaemia. This observation has been made studying both blood and bone marrow in
      children on widely differing treatment regimens from the 1970s to the present
      day. It appears to be independent of other classical prognostic factors such as
      age and diagnostic white cell count. Currently some major collaborative groups
      are using the rate of initial disease clearance to risk-stratify subsequent
      therapy and this practice may increase. The best way to measure the rate of
      disease clearance remains to be defined. Watching disappearance of peripheral
      blood blasts is the least invasive method but possibly the least sensitive.
      Molecular quantitation of minimal residual disease (MRD) after achievement of
      conventional remission is much more sensitive but less specific. It cannot be
      applied to all patients and is costly and time consuming. The degree of marrow
      infiltration remaining after 7 or 14 days may fall between the two but is often
      difficult to estimate reliably and reproducibly due to technical limitations. The
      three techniques may reflect response to therapy in a way slightly different from
      each other and may not be direct correlates. The best compromise may be to use
      all three but to reserve MRD study only for those who clear their blood and bone
      marrow after 7 days.

PMID- 9922041
TI  - Accumulation of methotrexate polyglutamates, ploidy and trisomies of both
      chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute
      lymphoblastic leukemia: a Pediatric Oncology Group Study.
AB  - Levels of accumulation of methotrexate polyglutamates were measured in vitro in
      lymphoblasts obtained at diagnosis from children with B-progenitor cell acute
      lymphoblastic leukemia (pro-B ALL). They were compared to numerical and
      structural chromosomal abnormalities present in these leukemic cells. In a series
      of 95 patients, the percent with high lymphoblast methotrexate polyglutamate
      levels increased with the increase in modal number of total chromosomes
      (p<0.001). Thus, lymphoblast methotrexate polyglutamate accumulation appeared to
      be closely linked to the extent of hyperdiploidy in childhood pro-B ALL.
      Lymphoblasts from 35 (88%) of the 40 children with hyperdiploid (>50 chromosomes)
      and 23 (88%) of 26 with hyperdiploid (DNA Index >1.16) pro-B ALL accumulated high
      levels of methotrexate polyglutamate, suggesting that they were more sensitive to
      methotrexate cytotoxicity. While children with hyperdiploid (DNA Index >1.16) pro
      B ALL have a good prognosis, those with trisomies of both chromosomes 4 and 10,
      almost all of whom are hyperdiploid, have an even better outcome. There was no
      significant difference in methotrexate polyglutamate levels in lymphoblasts from
      19 children with and 21 without trisomies of both chromosomes 4 and 10 (p =
      0.25). The improved response to multi-agent chemotherapy conferred by the
      presence of trisomies of both chromosomes 4 and 10 in such patients may be due to
      increased sensitivity of their lymphoblasts to one or more anti-leukemic agents
      in addition to methotrexate.

PMID- 9922042
TI  - Results of topotecan single-agent therapy in patients with myelodysplastic
      syndromes and chronic myelomonocytic leukemia.
AB  - The activity of topotecan was evaluated in patients with myelodysplastic syndrome
      (MDS) and chronic myelomonocytic leukemia (CMML). Sixty patients with a diagnosis
      of MDS (n = 30) or CMML (n = 30) were treated. Their median age was 66 years,
      with 50 patients (83%) being over 60 years of age at time of study entry.
      Chromosomal abnormalities were present in 50% of patients and thrombocytopenia of
      less than 50 x 10(9)/L in 50%. Topotecan was administered as 2 mg/m2 by
      continuous infusion over 24 hours daily for five days (10 mg/m2 per course) every
      4 to 6 weeks for two courses, then at maximum tolerated dose level (1-2 mg/m2 by
      continuous infusion over 24 hours daily for five days) once every 4-8 weeks for a
      maximum of 12 courses. Evaluation of outcome and of differences among subgroups
      was performed according to standard methods; the criteria for response were those
      used for acute leukemia. Nineteen patients (31%) achieved a complete response
      (CR). A CR was achieved in 11 of 30 patients with MDS (37%) and in eight of 30
      with CMML (27%). A CR was achieved in 10 of 23 patients with previously untreated
      MDS (43%). Eight of 11 patients who presented with cytogenetic abnormalities
      (five of which involved chromosome 5 and/or 7 abnormalities) and achieved CR,
      were evaluated cytogenetically in CR: all were cytogenetically normal in CR.
      Characteristics associated with a higher CR rate were lack of previous
      chemotherapy, absence of ras oncogene mutations, and presence of less than 10%
      monocytes in either peripheral blood or bone marrow. In contrast, CR rates were
      similar by different agent groups, by different karyotype abnormalities, and by
      other pre-therapy peripheral blood counts. Non-myelosuppressive side effects were
      mucositis in 67% of patients (severe [grade 3-4] 23%), diarrhea in 38% (severe
      17%), and nausea and vomiting in 28% (severe 5%). Febrile episodes during
      neutropenia occurred in 85% of patients and documented infections in 47 %.
      Mortality in the first four weeks was 20%. With a median follow-up duration of 31
      months, the 12 month survival rate was 38%, median survival time 10.5 months, and
      median remission duration 7.5 months. In summary, topotecan has significant
      single-agent activity in MDS and CMML. Complete responses associated with
      topotecan therapy often involve the disappearance of abnormal, poor-prognosis
      karyotypes, which is particularly encouraging. Future strategies to optimize
      topotecan's role include combination regimens with topoisomerase II reactive
      agents, cytarabine, or hypomethylating agents (azacytidine and decitabine).

PMID- 9922043
TI  - Cell cycle dependency of 67gallium uptake and cytotoxicity in human cell lines of
      hematological malignancies.
AB  - 67Gallium (67Ga) is a radionuclide which accumulates in hematological
      malignancies and is used for diagnostic imaging. We investigated in this in vitro
      study the cell cycle dependency of cellular uptake and cytotoxicity of 67Ga. Cell
      cycle synchronization of cells was achieved by counterflow centrifugal
      elutriation and the use of cytostatic drugs. The human lymphoma cell lines U-937
      and U-715 were used and in elutriation experiments we also used the leukemic cell
      line HL-60. The transferrin receptor (CD71) expression, 67Ga uptake and cell
      proliferation inhibition were the parameters measured. We also studied
      cytotoxicity in various schedules for combination of 67Ga and drugs and the
      residual proliferative capacity was measured. The CD71 expression in the three
      cell lines increased from 106-177% on S phase cells and from 118-233% on G2M
      cells, as compared to the G0/G1 cell fraction. The 67Ga uptake varied from 108
      127% for S cells and 128-139% for G2M cells. The drugs chosen induced cell cycle
      phase accumulation in S and/or G2M phase during preincubation. 67Ga preincubation
      induced accumulation in the G2M phase. Almost all combinations of 67Ga and drugs
      resulted in a non-interactive effect, except for methotrexate which resulted in
      an antagonistic effect. No preferential effect of any of the incubation schemes
      was seen. CD71 expression and 67Ga uptake were increased in S and G2M cells.
      Combination of 67Ga with drugs which arrest cells in these cell cycle phases did
      not result in a change in cytotoxicity. However, these results implicate that
      67Ga and the cytostatic drugs tested except for methotrexate might be used
      together or sequentially in therapy.

PMID- 9922044
TI  - Antileukemic effects of rapid cyclosporin withdrawal in patients with relapsed
      chronic myeloid leukemia after allogeneic bone marrow transplantation.
AB  - The results of rapid tapering of Cyclosporin therapy in 7 patients with
      Philadelphia chromosome-positive chronic myeloid leukemia (CML) in relapse after
      allogeneic bone marrow transplantation are reported. All patients had
      cytogenetically-documented relapse within 6 months of transplant, and were on
      oral Cyclosporin therapy. Rapid tapering of Cyclosporin resulted in moderately
      severe acute GVHD in 2 cases, and in extensive chronic GVHD in a further 2
      patients (fatal in 1 case). An antileukemic effect was observed in 6 patients,
      with complete haematological and cytogenetic remission observed in all cases. The
      seventh patient did not respond, and died after infusion of donor leucocytes.
      Four of the responders remain in complete remission of CML 30 to 120 months after
      BMT. One patient died in remission of chronic GVHD, and one patient had a
      complete response lasting 5 months, but relapsed and died 13 months post
      transplant. Rapid withdrawal of Cyclosporin therapy appears to be an effective
      means of treatment of early relapse of CML after transplant, and is an
      alternative to the use of donor leucocyte infusions for those patients still
      receiving Cyclosporin at the time of relapse.

PMID- 9922045
TI  - Blocking interleukin-6 activity with chimeric anti-IL6 monoclonal antibodies in
      multiple myeloma: effects on soluble IL6 receptor and soluble gp130.
AB  - Interleukin-6 (IL6) plays a major role in the pathogenesis of multiple myeloma.
      In patients with monoclonal gammopathy serum levels of sIL6R have been found to
      be increased. The role of IL6 in the regulation of soluble receptors is still
      unclear. In a phase I/II study we treated 12 myeloma patients with high-affinity
      chimeric anti-IL6 monoclonal antibodies. This treatment resulted in a total in
      vivo blockage of IL6 activity and as a result we had an unique opportunity to
      gain insight into the possible regulation effects of IL6 on these soluble IL6
      receptors. Pre-treatment sIL6R levels were elevated in 9 of the 12 patients; pre
      treatment sgp130 levels were significantly increased in all patients. Total
      blockage of IL6 activity by the high-affinity cMab did not influence sIL6R in 10
      of these 12 patients and sgp130 levels remained stable in all patients. Of the 2
      patients whose sIL6R levels increased during therapy, one had progressive disease
      and the other developed an acute infection. We conclude that in most end-stage
      myeloma patients sIL6R and sgp130 serum levels are elevated, but that there is no
      relation between IL6 activity and sIL6R or sgp130 levels.

PMID- 9922046
TI  - Aberrant rearrangements of the immunoglobulin heavy chain switch region in
      chronic B-cell leukemia.
AB  - Analysis of the organisation of the Cmu-switch region of the immunoglobulin heavy
      chain locus in B-lymphocytes from 80 patients with chronic B-cell leukemia
      revealed 25 patients with abnormal rearrangements that could not be explained by
      the normal recombination events that take place in B-lymphocytes. Detailed
      analysis with probes spanning the Cmu -switch region and various restriction
      digests localised the rearrangements in two thirds of the patients to a 1300 bp
      region at the 5' end of the switch region while in the remaining patients the
      rearrangements occurred in the switch region. The consequences of these aberrant
      rearrangements remain to be determined, but their clustering to a defined region
      of the switch region suggests a "hot spot" that may be involved in the aetiology
      of the disease.

PMID- 9922047
TI  - All patients with persistent polyclonal B cell lymphocytosis present Bcl-2/Ig
      gene rearrangements.
AB  - The bcl-2 gene belongs to a class of oncogenes involved in the inhibition of
      apoptosis. Most follicular lymphomas are associated with the t(14;18)
      translocation that juxtaposes the bcl-2 gene located on chromosome 18 to the
      immunoglobulin gene locus located on chromosome 14. Consequently, the bcl-2 gene
      is overly expressed and leads to an accumulation of mature clonal B cells.
      Prolonged survival of the B cell clone appears to be the early event in
      tumorigenesis, creating an increased risk of cumulative mutations. Interestingly,
      bcl-2/Ig gene rearrangements may be identified in nearly 50% of normal
      individuals but the outcome of normal individuals carrying high levels of
      t(14;18) is not well defined. Persistent polyclonal B cell lymphocytosis (PPBL)
      is a unique polyclonal lymphoproliferative disorder mostly restricted to women.
      We have recently demonstrated that PPBL is also associated with multiple bcl-2/Ig
      gene rearrangements. In this report, we have extended our analysis to additional
      patients and demonstrated that all patients presented multiple detectable
      t(14;18) translocated clones. In addition, Bcl-2 protein expression was
      increased. Our findings, along with the clinical features of PPBL, make this
      disorder an exceptional model for the study of B-cell homeostasis.

PMID- 9922048
TI  - Non-Hodgkin's lymphomas in Mexico. A clinicopathological and molecular analysis.
AB  - It is now well established that the clinical and histopathological
      characteristics of non-Hodgkin's lymphomas may vary significantly throughout the
      world. However, only a few reports have been published in Latin American
      countries. In this work, the clinical and pathologic findings of 264 patients
      with non-Hodgkin's lymphomas in Mexico City were analyzed. Diffuse large (14%)
      and diffuse mixed cell types (20%) predominated among nodal lymphomas. Within the
      group of patients with high grade malignancies, immunoblastic sarcomas were the
      most common (40/48). It is important to mention that follicular lymphomas were
      sporadic (4.5%). Among extranodal lymphomas the most commonly involved site was
      the gastrointestinal tract (11.3%), followed by the midline (6%). Molecular
      analysis of 65 cases with immunoglobulin and T-cell receptor gene probes showed
      that most lymphomas were of B-cell lineage (66%). The remaining group was
      composed of T-cell (25%) and bigenotypic malignancies (9%). All attempts to
      establish a correlation between the clinical stage and histopathological types
      with the genetic findings were not successful. However, pre-B and bigenotypic
      lymphomas were observed mainly in patients over 60 years of age. This study
      highlights some relevant characteristics of non-Hodgkin's lymphomas in Mexico.

PMID- 9922050
TI  - In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E
      and Z: studies on a human T-cell leukemia cell line and their resistant variants.
AB  - P-glycoprotein(P-gp)- related resistance is one of the major obstacles in
      treating leukemia patients. Therefore, it is of clinical interest to find new
      potential modulators and compare their P-gp-modulating efficacy. The present
      analysis investigated the influence of P-gp modulators, such as verapamil,
      tamoxifen, droloxifene E, droloxifene Z, SDZ PSC 833 (PSC 833) and dexniguldipine
      in a leukemic T-cell line (CCRF-CEM) and its P-gp-resistant counterparts (CCRF
      CEM/ACT400 and CCRF-CEM/VCR1000). P-gp expression was assessed with an
      immunocytological technique using the monoclonal antibody 4E3.16. It was
      characterized as the percentage of P-gp positive cells and also expressed as a D
      value by using the Kolmogorov Smirnov statistic. The efficacy of P-gp modulators
      was determined with the rhodamine-123 accumulation test and the MTT test. An in
      vitro modulator concentration between 0.1 microM and 3 microM was determined,
      where no genuine antiproliferative effect was apparent. The modulators PSC 833
      and dexniguldipine were the significant (p<C0.05) most potent chemosensitizers
      followed by verapamil, droloxifene Z, tamoxifen and droloxifene E in descending
      order. In addition to the modulators PSC 833 and dexniguldipine, droloxifene Z
      should especially be considered as a candidate for future ex vivo and in vivo
      studies. The main advantage of droloxifene Z could be the low rate of expected
      side effects. This fact permits the use of high Drol Z dosage in order to achieve
      a relevant modulating effect in vivo and to use this drug in combination with a
      further modulator so as to reach maximum efficacy with tolerable side effects.

PMID- 9922049
TI  - Systemic polychemotherapy in the treatment of primary cutaneous lymphomas: a
      clinical follow-up study of 81 patients treated with COP or CHOP.
AB  - The efficacy of systemic polychemotherapy in the treatment of primary cutaneous B
      cell lymphomas (CBCL) or T-cell lymphomas (CTCL) is still controversial. A series
      of 81 patients (46 primary CBCL and 35 CTCL) were treated with COP or CHOP
      regimens. In primary CBCL, the overall objective response rate (RR) was 98%, with
      an 89% CR rate and a 33% relapse-rate. Five-year disease-free survival was 70%, 5
      year survival 97%. Patients with leg or widespread lesions showed a higher
      relapse-rate (55% vs 26%) than those with trunk or head lesions. The overall
      objective RR was 40% in CTCL patients, with a 23% CR rate; median response
      duration was 5.7 months, median survival 19 months. The results confirm both the
      good prognosis of primary CBCL and the efficacy of polychemotherapy. CHOP regimen
      is to be preferred to COP in as much as it reduces relapse rates. Conversely,
      there are no indications for the use of COP/CHOP regimens as first-line
      chemotherapy in CTCL patients.

PMID- 9922051
TI  - Modulation of homeobox B6 and B9 genes expression in human leukemia cell lines
      during myelomonocytic differentiation.
AB  - Homeobox genes (HOX) may have a regulatory function in the differentiation
      process of hematopoiesis. We examined the change of HOX B6 and HOX B9 mRNA
      expressions during the in vitro differentiation of four myeloid leukemia cell
      lines because HOX B6 may be involved closely in myeloid differentiation. HL-60,
      NB4, NKM-1 and NOMO-1 were established from acute leukemia of M2, M3, M2 and M5
      subtype of the French-American-British classification, respectively. All-trans
      retinoic acid (ATRA), TPA, and G-CSF were used as differentiation inducers. Each
      cell line was cultured with each inducer and total RNA was isolated on day 1, 2,
      3, or 5. HOX B mRNA was detected by Northern blotting and RT-PCR methods. HOX B6
      and HOX B9 mRNAs were constitutively expressed in NB4, NKM-1 and NOMO-1, but were
      expressed at very low levels in HL-60. HOX B6 and HOX B9 mRNAs were also
      expressed in fresh acute myelocytic leukemia blasts. HOX B6 mRNA expression in HL
      60, NB4, and NKM-1 cultured with ATRA increased on day 3 and decreased on day 5.
      HOX B6 mRNA expression in NB4 and NKM-1 cultured with TPA decreased on day 3. HOX
      B9 mRNA expression displayed changes similar to those of HOX B6 mRNA in NB4 and
      NKM-1. These results indicate that myeloid leukemia cell lines express HOX B6 and
      HOX B9, and that their respective mRNA expressions in NB4 and HL-60 increase at a
      mid stage of myeloid differentiation by ATRA induction and then decrease during a
      late stage. HOX B6 mRNA expression decreased in monocytoid differentiation by TPA
      induction in NB4, HL-60 and NKM-1. HOX B6 antisense-oligonucleotide inhibited the
      proliferation of NB4 and NKM-1. These results suggest that HOX B gene expression
      is related to simultaneous activation of cellular proliferation and
      differentiation in leukemic cells.

PMID- 9922052
TI  - Non-Hodgkin's lymphoma associated with Gaucher's disease.
AB  - Gaucher's disease is an uncommon disorder which has been reported to be
      associated with an increased risk of lymphoproliferative disorders, including Non
      Hodgkin's lymphoma (NHL). A new instance of such an association is described
      here. This was a 58 year-old-patient with adult type I Gaucher's disease who, one
      and a half year after the above diagnosis, presented with supraclavicular
      lymphadenopathy, massive splenomegaly, prominent retroperitoneal lymphadenopathy
      and increased serum LDH levels. This led to the diagnosis of large-cell NHL of B
      cell type, successfully treated with chemotherapy. The previously published cases
      of Gaucher's disease associated with NHL as well as the possible mechanisms
      leading to this association are reviewed here.

PMID- 9922053
TI  - Sweet's syndrome during treatment with all-trans retinoic acid in a patient with
      acute promyelocytic leukemia.
AB  - A 46 year old male with acute promyelocytic leukemia treated with all-trans
      retinoic acid (ATRA), developed fever, bilateral erythematous nodules in his
      axillary area, lower abdomen and inguinal region. Histopathologic examination of
      the skin biopsy revealed dense neutrophil infiltration in the dermis without
      vasculitis. The diagnosis of Sweet's syndrome was made. High dose
      methylprednisolone was administered and the lesions started to improve within 24
      hours.

PMID- 9922054
TI  - Tetraploidy in acute myeloid leukemia secondary to large cell lymphoma.
AB  - A 67 year old male developed a therapy related myelodysplastic process
      culminating in acute myeloid leukemia 16 years following initial treatment for a
      large cell lymphoma. A second relapse of this leukemia showed 12% blasts
      including numerous giant blasts. The presence of giant blasts suggested the
      possibility of relapsed malignant lymphoma, however, flow cytometry and
      immunohistochemistry identified them as myeloid and chromosomal analysis revealed
      a near-tetraploid cell line. No evidence of lymphoma was seen. Although remission
      was induced with chemotherapy he subsequently relapsed with marrow and/or CNS
      involvement and was maintained on palliative therapy until he developed sepsis
      and died, 13 months following the observation of tetraploidy and 33 months
      following the onset of acute leukemia.

PMID- 9922055
TI  - Pneumococcal vaccination: perceptions of primary care physicians.
AB  - BACKGROUND: Little is known about barriers to pneumococcal vaccination in the
      primary care setting. METHODS: Mail survey to 405 randomly selected Massachusetts
      primary care physicians (response rate 68%). RESULTS: Seventy-nine percent
      considered themselves knowledgeable about current vaccination guidelines, and 75%
      said vaccination is an important clinical priority. Respondents answered a mean
      of five of six knowledge questions about vaccination "correctly," that is,
      consistent with current scientific evidence or expert opinion. Physicians
      reported high immunization rates: 51% thought over half their eligible patients
      were vaccinated; however, only 27% thought their colleagues immunized a similar
      number of patients. Physician attitude was the strongest independent predictor of
      high reported immunization rates (odds ratio of 4.7, P = 0.0001). Twenty-four
      percent of respondents thought physician oversight due to the need to attend to
      other active medical problems greatly reduces the number of patients they
      immunize. None of eight other financial, administrative, and clinical barriers
      were felt to be important by more than 7% of physicians. Sixty-six percent of
      physicians favored a standing order policy to immunize their eligible patients.
      CONCLUSIONS: Oversight and overestimation of immunization rates appear to be
      important barriers to pneumococcal vaccination. The literature suggests that
      reminder and performance feedback systems directed toward eliminating these
      barriers have had some success; interventions such as standing order policies may
      yield further improvements and appear to be acceptable to most physicians.

PMID- 9922056
TI  - A message from Preventive Medicine and your physician: Adults need shots, too!

PMID- 9922057
TI  - Normal growth in high-risk hyperlipidemic children and adolescents with dietary
      intervention.
AB  - OBJECTIVE: The aim of this study was to assess the safety and efficacy of
      lowering dietary intake of total fat, saturated fat, and cholesterol in growing
      children and adolescents with severe hyperlipidemia. STUDY DESIGN: This is a 3
      year follow-up study conducted on a sample of convenience at three pediatric
      referral centers in New York City and its suburbs. Subjects were 138 children and
      adolescents 2 to 15 years of age (54% male), who had been referred with a
      diagnosis of hyperlipidemia. Those selected had total serum cholesterol values
      greater than the 95th percentile for age and had at least three visits over 3
      years. They were placed on diets restricting total fat content to 30% of total
      calories and saturated fat to 10% of total calories (National Cholesterol
      Education Program Step I diet). Anthropometric measures, lipid profiles, and
      dietary assessment were obtained at each visit. Anthropometric data were analyzed
      by sex and age. Z scores for height and weight were calculated from NHANES II
      data and were compared by paired t tests (Hamill et al., 1979, Am J Clin Nutr
      32:607-29). RESULTS: Total serum cholesterol dropped from 262 mg/dL at baseline
      to 249 mg/dL at 3-year follow-up (P = 0.003). There was no significant change in
      height or weight percentile, expressed as Z score, from baseline to 3-year follow
      up. CONCLUSIONS: In this population the supervised dietary interventions resulted
      in a sustained improvement of the lipid profile, with no demonstrable adverse
      effect on growth.

PMID- 9922058
TI  - Three-year prospective adherence to three breast cancer screening modalities.
AB  - BACKGROUND: This study prospectively examined rates of adherence to mammography,
      clinical breast examination (CBE), and breast self-examination (BSE) in a cohort
      of women over 3 years to determine whether participation in BSE influenced
      participation in the other two screening modalities. METHODS: Women ages 51 and
      older (n = 450) who attended a small group educational session to learn BSE and
      to hear about CBE and mammography guidelines were assessed annually by telephone
      for 3 consecutive years to determine their subsequent breast cancer screening
      behavior. RESULTS: Annual CBE and mammography screening are highly positively
      associated. Regular performance of BSE has a modest positive association with
      both CBE and mammography adherence over time. CONCLUSIONS: Women who perform BSE
      regularly over time may be more likely to adhere to the other breast cancer
      screening guidelines.

PMID- 9922059
TI  - A cross-sectional study on the relationship between depression and left
      ventricular hypertrophy.
AB  - BACKGROUND: Despite a large number of studies, the relationship between
      depression and cardiovascular disease remains ambiguous. This study is the first
      to investigate the relationship between depression and left ventricular
      hypertrophy (LVH) as detected by electrocardiogram. METHODS: The subjects were
      346 male Japan Self-Defense Forces personnel ages 49 to 55 years. LVH was
      assessed by electrocardiogram. Depression was measured by the Self-Rating
      Depression Scale (SDS). Other selected risk factors were measured. Odds ratios
      for LVH in relation to selected variables were calculated. A logistic regression
      analysis was used to adjust for possible confounding variables. RESULTS: High
      level of depression (SDS score > or = 34) showed a high risk of LVH occurrence.
      After adjusting for BMI, systolic blood pressure, and/or diastolic blood
      pressure, there was a tendency toward a positive association of LVH with high
      level of depression. CONCLUSIONS: Our present study demonstrated that depression
      is closely related to LVH. Since LVH could be a predictor of fatal cardiovascular
      disease, this is of direct relevance to the prescription of preventive measures.

PMID- 9922060
TI  - Tobacco use and other risk behaviors among adolescents in an STD clinic.
AB  - BACKGROUND: This study examined the potential for tobacco use and other health
      risk behavior interventions in the context of an urban sexually transmitted
      diseases (STD) clinic. METHODS: A cross-sectional survey of two populations.
      Adolescents seen at an STD clinic or at the teen clinic of a community health
      center completed a self-administered computer survey in 1996. Risk behaviors,
      attitudes, and readiness to stop smoking were analyzed for 225 patients at the
      STD clinic and 248 patients at the teen clinic. RESULTS: Compared with
      adolescents in the teen clinic, adolescents in the STD clinic were more likely to
      have smoked frequently (OR 1.7, 95% CI 1.1, 3.0), used any illegal drug (OR 2.7,
      95% CI 1.3, 5.5), recently binged on alcohol (OR 1.7, 95% CI 1.0, 2.8), and had
      more than 10 lifetime sexual partners (OR 1.9, 95% CI 1.0, 3.4). Weapon carrying,
      readiness to stop smoking, and attitudes toward smoking did not differ between
      sites. CONCLUSIONS: Cigarette smoking and other health risk behaviors are more
      prevalent among adolescents in an STD clinic than among adolescents in a
      community health center. STD clinics are potential sites for cigarette, alcohol,
      and drug use interventions among "hard to reach" adolescents.

PMID- 9922061
TI  - Aerobic exercise and bone density at the hip in postmenopausal women: a meta
      analysis.
AB  - BACKGROUND: The effects of aerobic exercise on bone density at the hip in
      postmenopausal women in the absence of estrogen replacement therapy are not
      currently known. The purpose of this study was to examine the effects of aerobic
      exercise on bone density at the hip in postmenopausal women. METHODS: Using the
      meta-analytic approach, studies dealing with the effects of aerobic exercise on
      bone density at the hip in postmenopausal women were searched for using
      computerized literature searches (MEDLINE, January 1978 to December 1995) as well
      as cross-referencing from retrieved review articles and original investigations.
      RESULTS: A total of 18 effect sizes were derived from six studies. Using a fixed
      effects model and bootstrap resampling (5,000 iterations) overall changes in bone
      density at the hip yielded an average effect size of 0.43 (95% CI = 0.04 to
      0.81), equivalent to an overall change of approximately 2.42% (exercise = 2.13%;
      nonexercise = -0.29%). Statistically significant differences were observed when
      effect sizes were partitioned by country in which studies were conducted (United
      States, mean = 1.03, 95% CI = 0.48 to 1.68; other countries, mean = 0.18, 95% CI
      = -0.27 to 0.54; Qb = 5.44, P = 0.04) and calcium intake (> or =1,000 mg/day,
      mean = 0.83, 95% CI = 0.49 to 1.23; <1,000 mg/day = -0.23, 95% CI = -0.85 to
      0.21; Qb = 10.64, P = 0.002). CONCLUSIONS: The overall results of this study
      suggest that site-specific aerobic exercise has a moderately positive effect on
      bone density at the hip in postmenopausal women. However, a need exists for
      additional, well-designed studies before a final recommendation can be made
      regarding the efficacy of aerobic exercise as a nonpharmacologic intervention for
      optimizing bone density at the hip in postmenopausal women.

PMID- 9922063
TI  - Tuberculosis in South-East Asian refugees after resettlement--can prevention be
      improved by better policy and practice?
AB  - OBJECTIVE: This study aimed to determine whether incident cases of tuberculosis
      (TB) in a cohort of South-East Asian refugees followed for 5 years after
      resettlement were potentially preventable and whether prevention of TB was
      optimal in a state refugee TB screening program in Victoria, Australia. DESIGN: A
      retrospective cohort study of 1,101 refugees from Laos, Cambodia, and Vietnam
      screened for TB in the 6-month period from July 1989 to January 1990 was
      conducted. Incident cases of TB were identified by matching each refugee with the
      TB notification database for 5 years from the date of initial screening.
      Preventability was assessed for incident cases by reviewing medical records.
      Screening guidelines and practice were reviewed. RESULTS: The main outcome was
      the preventability of cases of active tuberculosis that developed in the study
      population in the first 5 years after resettlement. The incidence of active TB
      was 363/100,000 during the first year and 109/100,000/year during the first 5
      years. Five of six incident cases were assessed as potentially preventable, which
      if prevented would have resulted in an annual incidence of 18/100,000 over the
      first 5 years. Use of a more sensitive skin test definition of infection would
      have made an additional 245 refugees eligible for prevention and potentially
      prevented an additional 25 cases of TB over a lifetime. CONCLUSIONS: There is a
      high incidence of tuberculosis among SE Asian refugees, particularly in the first
      year after resettlement. A large proportion of TB may be preventable. Improvement
      in case prevention may be possible with updated guidelines and better
      implementation of screening policy.

PMID- 9922062
TI  - An instrument for assessing the quality of tobacco-control policies: the ACT-L
      scale.
AB  - BACKGROUND: Efforts to prevent and decrease tobacco use and tobacco-related
      disease include improving the quality of tobacco-control laws to make them more
      stringent in controlling tobacco advertising, youth access, and exposure to
      environmental tobacco smoke (ETS). However, because there are no instruments to
      empirically evaluate the quality of such laws, it has been difficult to
      demonstrate that their quality is associated with decreased youth access or
      tobacco-related morbidity. We present the first instrument for empirically
      assessing the quality of tobacco-control policies. METHODS: Recommendations for
      the content of an ideal, comprehensive tobacco-control policy were used as the 55
      items in the Assessment of the Comprehensiveness of Tobacco Laws Scale (ACT-L
      Scale). Raters evaluated 71 tobacco-control laws with the scale; 70 of these were
      actual California laws and 1 was a model law from Americans for Non-smokers'
      Rights (ANR). RESULTS: Interrater (r = 0.64-0.89) and internal-consistency (r =
      0.63-0.88) reliability of the scale and subscales were high, and validity was
      established by demonstrating that the ANR model law received a significantly
      higher total score (mean = 18.75) than all actual laws (mean = 2.04). California
      tobacco-control laws were poor in all areas (youth access, ETS, tobacco
      advertising). CONCLUSIONS: The ACT-L scale can be used to compare and evaluate
      the quality of tobacco-control laws, highlight areas in which further policy
      efforts are needed, quantify improvement in such policies, and empirically
      demonstrate the positive health impact of high-quality tobacco-control laws.

PMID- 9922064
TI  - Opening pathways to cancer screening for Vietnamese-American women: lay health
      workers hold a key.
AB  - PURPOSE: We describe a controlled trial of a community outreach intervention to
      promote recognition, receipt, and screening-interval maintenance of clinical
      breast examinations (CBE), mammograms, and Pap smears among Vietnamese-American
      women. METHODS: Over a 3-year period, indigenous lay health workers conducted
      small-group sessions of Vietnamese women in a low-income district of San
      Francisco, California. Women in Sacramento, California, served as controls. Lay
      workers conducted 56 sessions on general prevention, 86 on cervical cancer, and
      90 on breast cancer. Surveys of 306 to 373 women were conducted in the study
      communities in 1992 and 1996. RESULTS: In the intervention community, recognition
      of screening tests increased significantly between pre- and postintervention
      surveys: CBE, 50 to 85%; mammography, 59 to 79%; and Pap smear, 22 to 78% (P =
      0.001 for all). Receipt of screening tests also increased significantly: CBE, 44
      to 70% (P = 0.001); mammography, 54 to 69% (P = 0.006); and Pap smear, 46 to 66%
      (P = 0.001). Best-fitting logistic regression models, adjusting for
      preintervention rates and significant covariates, also showed statistically
      significant odds ratios for the intervention effect (P < 0.0001). CONCLUSIONS:
      Trained Vietnamese lay health workers significantly increased Vietnamese women's
      recognition, receipt, and maintenance of breast and cervical cancer screening
      tests.

PMID- 9922065
TI  - Impact of policy and practice on the effectiveness of contact screening for
      tuberculosis.
AB  - BACKGROUND: Screening for tuberculosis is conducted because TB is a disease of
      public health importance that can be prevented if screening is followed by
      isoniazid prophylaxis for infected individuals. Screening alone is not effective
      unless that screening is rational and systematic and is followed by prevention
      where appropriate. Our aim was to consider whether the TB contact screening
      guidelines are evidence-based and appropriate, how well these guidelines are
      implemented, and how policy and practice impact on prevention. METHODS: A cohort
      of 1,142 recent contacts screened in 1991 in Victoria, Australia, was studied. We
      evaluated the appropriateness of the screening guidelines and how well they were
      implemented and how the combination of these two factors impacted on the efficacy
      of the screening program. RESULTS: The screening guidelines required updating and
      were not evidence-based. Chest radiograph (CXR) was overused and was the sole
      screening tool for nearly 40% (449/1,142) of contacts. Eighty percent of repeat
      CXRs were done following a normal initial study. Skin testing was underused. In
      nearly 60% (658/1,142) of all contacts, the presence or absence of infection
      could not be determined because a skin test was not done and the CXR, if done,
      was clear. Only 22% (38/175) of identified, eligible contacts received isoniazid
      preventive therapy. CONCLUSIONS: Lack of evidence-based guidelines, as well as
      poor adherence to guidelines, resulted in an inefficient program. This problem
      may not be unique to the study setting, but cannot be identified without
      systematic program evaluation, for which we have provided a model.

PMID- 9922066
TI  - Quantitative assessment of recruitment efforts for prevention trials in two
      diverse black populations.
AB  - BACKGROUND: Prevention efforts to reduce the morbidity and mortality disparity
      between blacks and whites in the United States present a national health
      priority. However, participation of blacks in prevention trials has been low. The
      present study reports successful recruitment processes from two economically
      diverse black populations. METHODS: The two studies were independent projects,
      but both were part of a nationally funded collaboration on cardiovascular health.
      "Hip Hop to Health" is a 4-year randomized controlled trial aimed at dietary fat
      reduction and increased exercise among inner-city black families. The Fat
      Reduction Intervention Trial in African-Americans project is a 5-year trial to
      reduce total fat, saturated fat, and cholesterol intake among black families from
      a working class community. RESULTS: The two populations differed on demographic
      characteristics. Direct presentation was the most effective recruitment strategy
      in the "Hip Hop to Health" program. In contrast, telephone recruitment and
      neighborhood canvassing were the more successful strategies for FRITAA.
      CONCLUSIONS: Although both populations were black and at comparable
      cardiovascular disease risk, the differing demographics between the groups made
      different recruitment strategies necessary. This study documented the labor
      intensive quality of successful recruitment, and results suggest that successful
      recruitment requires strategies tailored to the needs, experiences, and
      environment of the target group.

PMID- 9922067
TI  - Characteristics of patients adhering to a hospital's no-smoking policy.
AB  - OBJECTIVES: The purpose of this paper is to examine the characteristics of
      smokers who adhere to a hospital smoking ban, compared to those who do not.
      DESIGN: The data presented in this paper are baseline and discharge survey data
      collected among hospitalized smokers. SETTING: This study was conducted in two
      teaching hospitals in a northeastern city. PATIENTS/PARTICIPANTS: The subjects
      were 358 smokers who participated in a larger smoking intervention trial. MAIN
      RESULTS: Seventy-six percent of the subjects reported adhering to the smoke-free
      policy during their hospital stay. In a multivariate model, demographic factors
      that predicted adherence included being older, having shorter length of stay, not
      reporting recreational drug use in the previous 12 months, and not having alcohol
      related problems. Smoking history variables that predicted adherence included
      having had at least 24 h of abstinence in the 7 days prior to hospitalization;
      self-efficacy variables (e.g., confidence in ability to quit smoking in 1 month
      and less anticipated difficulty refraining from smoking during hospitalization)
      also predicted adherence. CONCLUSIONS: Understanding the factors that predict
      adherence to health care policies can provide useful information for health
      promotion interventions in a medical setting. The implications of these findings
      are discussed.

PMID- 9922068
TI  - Smoking trends in the United States between 1969 and 1995 based on patients
      hospitalized with non-smoking-related diseases.
AB  - BACKGROUND: This study examines smoking trends in the United States by race,
      gender, education, and occupation. METHODS: The data were collected between 1969
      and 1995 through a hospital-based case-control study on tobacco-related cancers,
      including 21,057 male and 14,448 female control subjects who had been diagnosed
      of non-smoking-related diseases. Smoking measures were adjusted through direct
      standardization and regression methods. RESULTS: Despite the decline in smoking,
      daily cigarette consumption remained high among current smokers. Women's smoking
      prevalence decreased more slowly than men's and their age at smoking initiation
      also declined, while the inverse effects on smoking by education and occupation
      were more pronounced in men than in women. Smoking prevalence was higher, but
      daily cigarette consumption was lower in blacks compared to caucasians.
      CONCLUSIONS: Despite an overall downward trend in smoking, lung cancer remains a
      major public health concern, particularly among women, blacks, and white men with
      low education. The development of a systematic mechanism for more detailed,
      regular monitoring of tobacco use by various subpopulations is, therefore,
      crucial to future public health planning.

PMID- 9922069
TI  - A randomized community trial to increase mammography utilization among low-income
      women living in public housing.
AB  - BACKGROUND: A randomized trial was conducted to evaluate the impact of a
      community-based intervention on mammography use among low-income women living in
      public housing. METHODS: All 41 public housing high-rise buildings were
      randomized to treatment and delayed treatment (control) conditions. After a cross
      sectional baseline survey, an intervention called Friend to Friend was conducted
      in the treatment buildings by American Cancer Society and building resident
      volunteers. The intervention consisted of a health professional talk, small group
      discussions, and an opportunity to request assistance in obtaining a mammogram or
      mammogram reminder. A second cross-sectional survey was conducted to measure
      differences in screening rates between the study groups. RESULTS: Participation
      in the intervention averaged 27%. The study groups were equivalent at baseline.
      At follow-up, the proportion of women age 50-79 years who reported mammography
      screening in the previous 15 months was significantly higher in the treatment
      group (64%) than in the control group (52%). Breast cancer knowledge, attitudes,
      and beliefs did not differ between groups. CONCLUSIONS: These findings suggest
      that a multidimensional intervention which reaches women within their social
      environment and uses community volunteers can increase mammography utilization
      among women in public housing.

PMID- 9922070
TI  - Smoking as a risk factor for injury death: a meta-analysis of cohort studies.
AB  - BACKGROUND: Injury and tobacco effects represent one-quarter of the global burden
      of disease. Understanding the causes of injury and the effects of smoking may
      help reduce those burdens. Some smokers have high risks of injury. We provide an
      initial meta-analysis of cohort associations between smoking and fatal injury.
      METHODS: Three authors independently searched MEDLINE, and bibliographies of the
      pertinent studies found, for cigarette smoker-specific injury death data which
      allowed estimation of an appropriate relative risk (RR) and 95% confidence
      interval (CI). Relative risks and dose response were summarized by fixed effects
      and Poisson modeling, respectively. RESULTS: Six studies covering 10 pertinent
      cohorts were located. Associations between smoking and injury death have been
      significant after adjustment or, in effect, stratification for age, race, sex,
      country, and, respectively, alcohol, marriage, education, and body mass; job and
      time period; job, alcohol, and exercise; etc. Summary dose-response trends were
      significantly positive (P < 0.00005). Cigarette smoking predicted summary injury
      death crude RRs of 1.61 (CI 1.44-1.81) vs never smokers and 1.39 (CI 1.25-1.55)
      vs ex-smokers. CONCLUSIONS: Smoking has significant, consistent, dose-response,
      often strong and independent, prospective associations with injury death,
      internationally.

PMID- 9922071
TI  - Distributions and trends of serum lipid levels among United States children and
      adolescents ages 4-19 years: data from the Third National Health and Nutrition
      Examination Survey.
AB  - BACKGROUND: Atherosclerosis begins in childhood and progresses into adulthood.
      The reduction of cardiovascular risk factors, such as elevated serum total
      cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, in childhood
      may reduce cardiovascular morbidity and mortality in adulthood. Lipid
      distributions among children and adolescents were examined using the most recent
      nationally representative data. METHODS: Data from 7,499 examinees in NHANES III
      (1988-1994) were used to estimate mean and percentile distributions of serum
      total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and
      triglycerides in children and adolescents aged 4 to 19 years. The estimates were
      analyzed by age, sex, and race/ethnic groups. Trends in mean total cholesterol
      were examined for 12- to 17-year-olds using data from NHES III (1966-1970),
      NHANES I (1971-1974), and NHANES III (1988-1994). RESULTS: For children and
      adolescents 4 to 19 years of age, the 95th percentile for serum total cholesterol
      was 216 mg/dL and the 75th percentile was 181 mg/dL. Mean age-specific total
      cholesterol levels peaked at 171 mg/dL at 9-11 years of age and fell thereafter.
      Females had significantly higher mean total cholesterol and LDL-C levels than did
      males (P < 0.005). Non-Hispanic black children and adolescents had significantly
      higher mean total cholesterol, LDL-C, and HDL-C levels compared to non-Hispanic
      white and Mexican American children and adolescents. The mean total cholesterol
      level among 12- to 17-year-olds decreased by 7 mg/dL from 1966-1970 to 1988-1994
      and is consistent with, but less than, observed trends in adults. Black females
      have experienced the smallest decline between surveys. CONCLUSIONS: The findings
      provide a picture of the lipid distribution among U.S. children and adolescents
      and indicate that, like adults, adolescents have experienced a fall in total
      cholesterol levels. Total cholesterol levels in U.S. adolescents declined from
      the late 1960s to the early 1990s by an average of 7 mg/dL. This information is
      useful for planning programs targeting the prevention of cardiovascular disease
      beginning with the development of healthy lifestyles in childhood.

PMID- 9922072
TI  - A sustainable behavioral intervention to increase condom use and reduce gonorrhea
      among sex workers in Singapore: 2-year follow-up.
AB  - BACKGROUND: Prostitution is the most important source of transmission of AIDS and
      sexually transmitted diseases in Asia. We developed and evaluated the
      sustainability of an intervention to increase condom use and reduce gonorrhea
      among brothel-based sex workers in Singapore. The intervention focused on
      developing sex workers' negotiation skills, educating clients, and mobilizing
      support from peers and health staff in promoting condom use. METHODS: A pretest
      posttest design with one intervention site (n = 124) and another comparable
      control site (n = 122) was maintained for 5 months followed by a time series
      design to follow up the intervention group for 2 years. RESULTS: At 5 months, the
      intervention group improved significantly in negotiation skills and were almost
      twice as likely as controls to always refuse unprotected sex (adjusted rate ratio
      1.90, 95% CI 1.22-2.94). Gonorrhea incidence declined considerably by 77.1% in
      the intervention group compared with 37.6% in the controls. Consistent refusals
      of unprotected sex in the intervention group increased from 44.4% at baseline to
      65.2% at 5 months, 73.6% at 1 year, and 90.5% at 2 years with a corresponding
      decline in gonorrhea. CONCLUSION: Sustained condom use with a corresponding
      decline in gonorrhea was achieved by a behavioral and environmental intervention
      for sex workers.

PMID- 9922073
TI  - Defective regulation of leukemic hematopoiesis in chronic myeloid leukemia.
AB  - Over the last two decades considerable knowledge has been acquired about the
      distribution of cell types within the dominant leukemic (Ph+/BCR-ABL+) clone that
      results in human chronic myeloid leukemia (CML). Evidence is now growing to
      indicate that three key biological changes affecting the development of such
      clones are: (1) an increased probability of differentiation at the level of the
      most primitive leukemic stem cells; (2) an increased turnover rate of the
      leukemic progenitors at all stages of differentiation: and (3) their increased
      ability to survive under conditions of factor-deprivation. Such a model explains
      the long latent period for the development of CML as well as why normal stem
      cells may persist in large numbers but still fail to compete in contributing to
      the daily output of mature blood cells in patients with disease. The recent
      development of new genetic and transplant models of human CML may now allow the
      molecular basis of these biological disturbances to be delineated and more
      effective therapeutic strategies developed.

PMID- 9922074
TI  - Hemopoietic growth factor receptor abnormalities in leukemia.
AB  - Growth factor and cytokine control of hemopoiesis, the process of blood cell
      development, is mediated by specific interactions with cell-surface receptors.
      Hemopoietic growth factor receptors belong to two major families, the
      transmembrane protein tyrosine kinases and the hemopoietin receptors. Ligand
      binding stimulates receptor aggregation and activation resulting in transduction
      of signals that induce diverse cellular responses including proliferation,
      maturation, prevention of apoptosis and/or functional activation. Deregulation of
      hemopoiesis can result in leukemia, the malignant transformation of blood cells,
      or the development of other hemoproliferative disorders. As hemopoietic growth
      factor receptors are integral to blood cell regulation, it is feasible that
      receptor abnormalities may contribute to leukemia by circumventing normal growth
      factor control or altering the balance of proliferation and differentiation.
      Although considerable experimental evidence has clearly established the
      leukemogenic potential of mutated growth factor receptors, studies to date
      suggest that such abnormalities contribute only rarely to human disease.

PMID- 9922075
TI  - Molecular abnormalities in myeloid leukemias and myelodysplastic syndromes.
AB  - Analysis of chromosome translocations in human myeloid leukemias and
      myelodysplastic syndromes has identified a number of genes involved in the
      pathogenesis of these diseases. Most of the genes identified to date can be
      grouped into one of three major classes--transcription factors, tyrosine kinases
      or nuclear pore proteins. Recent insights into the molecular basis of these
      leukemias is presented using selected examples from these groups.

PMID- 9922076
TI  - Apoptosis and its role in the myelodysplastic syndromes: implications for disease
      natural history and treatment.
AB  - Apoptosis (programmed cell death) is an active cellular process which regulates
      cell population size by decreasing cell survival. In this review the underlying
      cellular and molecular mechanisms of apoptosis in hemopoietic and non-hemopoietic
      cells are described, with specific focus on these issues in the myelodysplastic
      syndrome (MDS), a myeloid clonal hemopathy. Apoptosis-regulating genes exist as
      families whose protein products are either anti-apoptotic or pro-apoptotic.
      Numerous stimuli can serve as initiators of the cell death pathway, including
      essentially all chemotherapeutic drugs, irradiation, certain inhibitory cytokines
      and deprivation of relevant growth factors. Morphological evidence of increased
      apoptosis in marrow hemopoietic cells has been demonstrated in patients with MDS.
      The reviewed data provide support for the hypothesis that early in MDS, increased
      apoptosis is associated with ineffective progenitor and maturing hemopoietic cell
      survival, and occurs concomitant with cytopenias/ineffective hemopoiesis;
      conversely, the progression of MDS toward AML occurs in concert with decreased
      apoptosis and an increased degree of neoplastic cell survival, leading to
      subsequent expansion of the abnormal precursor cells. These processes are
      associated with alterations in the balance between pro- and anti-apoptotic
      oncoprotein expression within the hemopoietic precursors, which may be modified
      by cytokine treatment. Investigations evaluating apoptotic events in MDS have
      improved our understanding of the biology of hemopoietic cell survival as related
      to pathogenetic features of this disease. By modifying levels of apoptosis, such
      studies provide a framework for future potentially beneficial therapeutic
      approaches to treat patients with MDS.

PMID- 9922077
TI  - Granulocyte colony-stimulating factor in combination with intensive chemotherapy
      in the treatment of acute myeloid leukemia.

PMID- 9922078
TI  - Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating
      factor and macrophage colony-stimulating factor in the treatment of acute myeloid
      leukemia and acute lymphoblastic leukemia.
AB  - The role of G-CSF, GM-CSF and M-CSF in the treatment of AML and ALL was reviewed.
      These CSFs significantly accelerate the neutrophil recovery after intensive
      chemotherapy, and reduce febrile neutropenia and documented infections. There is
      no clear evidence that CSFs accelerate early regrowth of AML cells at the doses
      and schedules presently used clinically except one study. Patients who have
      received CSFs tend to have a higher CR rate, which does not seem to be translated
      into definite survival benefit. There has been no prospective randomized study
      showing any beneficial priming effect of CSFs on AML cells with better clinical
      outcomes.

PMID- 9922079
TI  - Thrombopoietic factors potentially useful in the treatment of acute leukemia.
AB  - Thrombocytopenia is a major cause of morbidity following intensive chemotherapy
      for acute leukemia. Over recent years, there has been an increasing use of
      platelet transfusions which, although generally efficacious to prevent severe
      hemorrhage, have associated risks of transmitting blood-borne disease and of
      alloimmunization. Therefore, there is a clinical requirement for a drug that will
      reliably alleviate the thrombocytopenia associated with leukemia therapy. The c
      mpl ligand thrombopoietin is the most interesting factor for the treatment of
      thrombocytopenia because of its lineage specificity. Phase I and II studies
      confirm its biological efficacy to induce rise in platelet count in patients with
      solid tumors and acute leukemia. Several other pleiotropic hematopoietic growth
      factors are also currently in clinical trials. These include interleukin-6,
      interleukin-3, interleukin-11, PIXY321 and stem cell factor. The effects of these
      cytokines appear to be modest at most and, with the exception of interleukin-11,
      their side effects are likely to limit their clinical application. Combinations
      of factors may prove more efficacious approaches to enhance platelet recovery.

PMID- 9922080
TI  - Interleukin 2 in the treatment of acute leukemia.

PMID- 9922081
TI  - Growth factors in the treatment of acute lymphoblastic leukemia.
AB  - The safety of G-CSF and GM-CSF in adult and pediatric patients with ALL has been
      well established. In addition, prophylactic administration of G-CSF was shown to
      significantly accelerate neutrophil recovery in most clinical trials. This was
      associated with a substantially reduced incidence and duration of febrile
      neutropenia and of severe infections in selected high risk patients receiving
      multiple treatment cycles, whereas the clinical benefit appears to be negligible
      in patients at low risk of infectious complications. There is currently
      insufficient evidence to support the use of GM-CSF as an adjunct to treatment for
      ALL outside of clinical trials. Apart from patient characteristics and type of
      CSF, it has become evident that scheduling of growth factor administration in
      relation to the type of chemotherapy, and use of different study end points
      influence the clinical efficacy of HGF administration. Although no studies have
      so far shown that use of growth factors is associated with reduced mortality,
      higher complete remission rates or superior survival, improvements in other
      clinical endpoints, e.g. infection rate, duration of i.v. antibiotics, and length
      of hospital stays were frequently perceived as clinically important and felt to
      contribute substantially to the patient's quality of life. It will become
      increasingly important to select those patients likely to benefit from growth
      factor support and to identify additional predictive criteria. Scheduling of
      CSFs, e.g. early versus delayed and prophylactic versus interventional
      administration, the type of growth factor used and the duration of administration
      need to be optimized in the context of specific treatment protocols. Although
      myeloid growth factors presently can not be expected to have a major impact on
      overall treatment outcome in patients with ALL, they facilitate important
      incremental improvement; in supportive care when appropriately applied. As the
      remaining open questions are resolved, clinical benefits may be achieved
      consistently and with a favorable cost benefit ratio.

PMID- 9922082
TI  - Polysomnography and maintenance of wakefulness test as predictors of CPAP
      effectiveness in obstructive sleep apnea.
AB  - Nasal continuous positive airway pressure (CPAP) therapy is usually effective in
      the treatment of obstructive sleep apnea (OSA), reversing the excessive daytime
      sleepiness associated with OSA. We investigated how polysomnography and
      maintenance of wakefulness test (MWT) predicted response to CPAP therapy in 10
      patients with obstructive sleep apnea and 10 healthy controls. After a full
      polysomnography and MWT the patients were started on CPAP. MWT was repeated to
      quantify the treatment effect. Oxygen desaturation index and the percentage of
      slow wave sleep were the best predictors for baseline S1 latency in MWT. Baseline
      S1 latency in the MWT was the most important determinant of improvement in MWT S
      latency after CPAP, followed by the latency to 10 min of continuous nocturnal
      sleep, arousal index and CPAP use. We suggest that in mild sleep apnea, knowledge
      of sleep architecture is not necessary before deciding whether or not to initiate
      CPAP treatment.

PMID- 9922084
TI  - EOG correction: a new aligned-artifact average solution.
AB  - OBJECTIVE: In the field of EOG correction, discrepancies have been found between
      the propagation rates for different types and frequencies of eye movement.
      However, Croft and Barry demonstrated that these differences can be explained by
      the affect of EOG magnitude on the correction procedure (Croft, R.J. and Barry,
      R.J. EOG correction: a new perspective. Electroenceph. clin. Neurophysiol., 1998,
      107: 387-394). This study utilized a new 'aligned-artifact average' technique
      (AAA) to examine whether propagation is constant across eye movement types and
      frequencies, and tested the AAA as an EOG correction tool. METHODS: Two
      experiments manipulated interference levels in real data sets to determine if
      interference affected propagation coefficients (Bs). The third tested real data
      for the effect of forward propagation of eye movement related neural potentials
      on Bs, and the fourth utilized computer simulations to assess the effectiveness
      of the new AAA correction procedure. RESULTS: Interference was found to inflate B
      at low EOG amplitude, and its removal removed B variation and inflation. The
      forward propagation of eye movement related neural potentials had very little
      effect on B. The AAA procedure produced near perfect corrections of the simulated
      data, superior to a comparison method. CONCLUSIONS: EOG propagation is constant
      across eye movement types and frequencies, and thus only one correction
      coefficient should be calculated and applied to data. The AAA method provides a
      more accurate correction and makes possible, for the first time, the adequate
      correction of posterior sites.

PMID- 9922083
TI  - EOG correction: a new perspective.
AB  - OBJECTIVE: In the field of EOG correction, discrepancies have been found between
      the propagation rates for different types and frequencies of eye movement. This
      study attempted to determine whether these differences could be explained by the
      affect of EOG magnitude on the correction procedure. METHODS: Experiment 1
      utilized simulated data to determine whether the combination of EOG magnitude and
      other forms of interference distorted the estimation of the propagation
      coefficients (Bs). Experiment 2 used real data to determine if the patterns
      obtained in Expt. 1 were apparent in real data. RESULTS: Matched t tests found
      that simulated low power EOG produced inflated Bs as a function of interference
      in Expt. 1. Experiment 2 found the same relationship between B and EOG magnitude
      as with the simulations. CONCLUSIONS: The findings are consistent with the thesis
      that eye movement related fields propagate similarly for a range of EOG types and
      frequencies, suggesting that the B differences reported in the literature are
      artifactual, and indicating the need for a new correction procedure.

PMID- 9922085
TI  - Reversible focal MRI abnormalities due to status epilepticus. An EEG, single
      photon emission computed tomography, transcranial Doppler follow-up study.
AB  - We demonstrate clinical data and findings of MRI, transcranial Doppler (TCD),
      single photon emission computed tomography (SPECT) and electroencephalography
      (EEG) in an 8 month follow-up study of a 15 year old girl who developed focal
      status epilepticus with sensory and visual illusions. EEG showed right temporal
      and occipital seizure activity and attenuation of the alpha activity with right
      predominance. MRI showed a right temporo-parietal hyper signal on the T2 weighted
      images involving the cortex with sulcal effacement. MRI-angiography suggested
      insufficient flow in the right transverse sinus. TCD detected an elevated flow
      velocity in the ipsilateral middle cerebral artery during status epilepticus,
      corresponding to an increased perfusion of the epileptic area revealed by SPECT.
      After normalization of the TCD finding, the MRI detected persistent cortical
      abnormality beyond the 70th day after admission. MRI normalized on the 103rd day
      of follow-up. Serial EEG frequency analysis demonstrated the recovery of alpha
      peak frequency on the left side, but the attenuation of rhythmic signals remained
      persistent on the right. In our case, the restitution of postictal EEG lag behind
      the consolidation of MRI signal abnormality.

PMID- 9922086
TI  - Assessing the accuracy of topographic EEG mapping for determining local brain
      function.
AB  - OBJECTIVE: There has been considerable discussion regarding the accuracy of
      topographic electroencephalographic (EEG) maps for assessing local cerebral
      function. We performed this study to test the accuracy of EEG mapping by
      examining the association between electrical activity and the perfusion under
      each electrode as another measure of local cerebral function. METHODS: EEG
      mapping was performed simultaneously with (H15)2O positron emission tomography
      (PET) scanning in 6 normal adult subjects, both at rest and during a simple motor
      task. EEG data were processed using 3 different montages; two EEG power measures
      (absolute and relative power) were examined. RESULTS: Relative power had much
      stronger associations with perfusion than did absolute power. In addition,
      calculating power for bipolar electrode pairs and averaging power over electrode
      pairs sharing a common electrode yielded stronger associations with perfusion
      than data from referential or single source montages. CONCLUSIONS: These findings
      indicate (1) that topographic EEG mapping can accurately reflect local brain
      function in a way that is comparable to other methods, and (2) that the choice of
      EEG measure and montage have a significant influence on the degree with which
      maps reflect this local activity and function.

PMID- 9922087
TI  - From the 'EEG age' to a rational scale of brain electric maturation.
AB  - The aim of the present study was to propose an improved method of quantitative
      assessment of EEG age-related changes. 40 EEG recordings of healthy subjects
      (aged 0.7-78 years) were analysed. Multidimensional scaling of EEG spectral data
      indicated a presence of an 'age factor' related non-linearly to the chronological
      age. Relative integrals of FFT spectra in 6 frequency bands were utilized as
      predictors of age or, alternatively, logarithmized age. Three regression models
      based on EEG spectral indicators were examined. Regression from logarithmic
      predictors to logarithm of age performed best in terms of linearity and residual
      errors. As a result, the Brain Electric Maturation Scale was proposed, being
      defined by the logarithm of ratio of the age predicted from the EEG data and
      chronological age. The scale could serve as an objective measure of brain
      maturation in children, or as an age-independent indicator of slow EEG
      abnormalities.

PMID- 9922088
TI  - Epilepsies and video games: results of a multicentric study.
AB  - OBJECTIVES: The purpose of this study was to research whether or not video games
      may induce paroxysmal discharges (PD) in different groups of patients. METHODS:
      One hundred and fifteen subjects from 5 different French laboratories were
      studied: 33 had seizures exclusively under visual stimuli, 42 had both photogenic
      seizures and spontaneous seizures occuring independently, and 40 had non
      photogenic seizures. The same protocol which included one TV sequence, 3
      sequences of video games selected on particular criteria (pattern, luminosity and
      nature of the scene), were presented at different distances from the TV screen at
      50 and 100 Hz. RESULTS: Among the factors provoking paroxysmal discharges (PD)
      some seem crucial: the frequency of the TV screen (the 100 Hz screen was
      significantly safer than 50 Hz), the distance from the screen (1 m safer than 50
      cm), and, particularly for the 50 Hz screen, the specific pattern of the images
      and the act of playing. CONCLUSIONS: Video games are ineffective for subjects
      known as having a non-photosensitive epilepsy, but may induce PD on subjects
      known as photosensitive even when intermittent light stimulation (ILS) is not
      effective. These results based on a different approach than in other publications
      confirm data which were suggested by the literature, and suggest that 100 Hz TV
      screens should be recommended to patients with TV-induced attacks.

PMID- 9922089
TI  - EEG-based communication: analysis of concurrent EMG activity.
AB  - OBJECTIVE: Recent studies indicate that people can learn to control the amplitude
      of mu or beta rhythms in the EEG recorded from the scalp over sensorimotor cortex
      and can use that control to move a cursor to targets on the computer screen.
      While subjects do not move during performance, it is possible that inapparent or
      unconscious muscle contractions contribute to the changes in the mu and beta
      rhythm activity responsible for cursor movement. We evaluated this possibility.
      METHODS: EMG was recorded from 10 distal limb muscle groups while five trained
      subjects used mu or beta rhythms to move a cursor to targets at the bottom or top
      edge of a computer screen. RESULTS: EMG activity was very low during performance,
      averaging 4.0+/-4.4% (SD) of maximum voluntary contraction. Most important, the
      correlation, measured as r2, between target position and EMG activity averaged
      only 0.01+/-0.02, much lower than the correlation between target position and the
      EEG activity that controlled cursor movement, which averaged 0.39+/-0.18.
      CONCLUSIONS: These results strongly support the conclusion that EEG-based cursor
      control does no depend on concurrent muscle activity. EEG-based communication and
      control might provide a new augmentative communication option for those with
      severe motor disabilities.

PMID- 9922090
TI  - Chronic periodic lateralized epileptiform discharges during sleep in a patient
      with caudate nucleus atrophy: insights into the anatomical circuitry of PLEDs.
AB  - OBJECTIVE: Periodic lateralized epileptiform discharges have been recognized for
      33 years; however, little is known about the underlying mechanism causing
      periodic discharges. The following case provides an opportunity to study PLEDs in
      a patient with precisely localized subcortical grey matter lesions. METHODS:
      Routine EEGs and overnight polysomnography were performed on the study patient.
      Standard 10-20 electrode positions were used, as well as EOG and chin EMG for
      polysomnography. RESULTS: The study patient was a 39-year-old woman with severe
      left caudate nucleus atrophy and right hemi-dystonia. She had left ventral
      lateral (VL) thalamotomies in 1989 and 1991, pallidotomy in 1992, and
      centromedian thalamic stimulator implantation in 1997. EEGs prior to surgical
      intervention demonstrated left hemisphere PLEDs during sleep. Following CM
      nucleus stimulatory implantation, the patient had overnight polsomnography. EEG
      during wakefulness and REM sleep was normal. With stages I-IV sleep left
      hemisphere PLEDs at 1-2 Hz were seen with fronto-temporal predominance. Sleep
      spindles were present bilaterally. There was no history of seizures, before or
      after surgery. CONCLUSIONS: The finding of PLEDs confined to synchronized sleep
      which were not affected by surgical manipulation of the motor basal ganglia
      circuit suggests a role of the associative basal ganglia circuit in the
      generation of periodic phenomenon.

PMID- 9922091
TI  - Cyclic alternating pattern (CAP) in normal sleep: polysomnographic parameters in
      different age groups.
AB  - OBJECTIVES: The present study aimed at offering a standardized database for
      cyclic alternating pattern (CAP) parameters across representative ages of life.
      METHODS: CAP parameters were quantified in 40 healthy sleepers and
      polygraphically investigated in a partially sound-proof recording chamber under a
      standard laboratory setting. Four age groups were investigated (teenagers: 10-19
      years; young adults: 20-39 years; middle-aged: 40-59 years; elderly: 60 years).
      Each group included 10 subjects (5 males and 5 females). Nocturnal recordings
      were accomplished after adaptation to the sleep laboratory that also served to
      rule out the presence of sleep-related disorders. The study indicated that CAP is
      a natural phenomenon of NREM sleep, with specific age-related characteristics
      across the life cycle. RESULTS: CAP rate in NREM sleep, defined as the percentage
      ratio of total CAP time to total NREM sleep time, showed a U-shape profile with
      minimum in young adults (31.9%), maximum in the elderly group (55.3%), and
      intermediate values in teenagers (43.4%) and in middle-aged subjects (37.5%). The
      longest duration of CAP cycles was found among the older subjects (31 s). The
      highest amounts of subtypes A1 were identified in teenagers (n = 261), while the
      highest amounts of A2 and A3 subtypes occurred in the elderly group (n = 183).
      Across the ages, the level of arousal mostly fluctuated in stages 1 and 3,
      whereas stage 4 emerged as the most stable NREM stage. Overall, stage 2 better
      reflected the CAP values referred to as total NREM sleep. CONCLUSIONS: The
      periodic arousal fluctuations reflected by CAP are a natural phenomenon of NREM
      sleep with specific age-related variations across the life cycle.

PMID- 9922092
TI  - The role of anti-Mullerian hormone in gonadal development.
AB  - Anti-Mullerian (AMH), a member of the transforming growth factor beta produced by
      immature Sertoli cells and, to a lesser degree, by granulosa cells from birth to
      the end of reproductive life, does not affect gonadal determination but has a
      negative effect upon gonadal development in both sexes. It blocks meiosis in
      fetal ovaries, leading to loss of germ cells and subsequent fibrous degeneration,
      and inhibits the transcription of aromatase and LH receptor. AMH also affects the
      development and function of the adult testis by blocking the differentiation of
      mesenchymal into Leydig cells and by independently decreasing the expression of
      steroidogenic enzymes.

PMID- 9922093
TI  - Role of cyclic nucleotide phosphodiesterases in resumption of meiosis.
AB  - In the follicles of the mammalian and amphibian ovary, oocyte maturation is
      arrested at the prophase of the first meiotic division. Prior to ovulation,
      oocytes reenter the cell cycle, complete the meiotic division, and extrude the
      first polar body. Work from several laboratories including ours has provided
      evidence that the cAMP-mediated signal transduction pathway plays an important
      role in regulation of meiosis, the cyclic nucleotide acting as a negative
      regulator of maturation. Since cAMP can be regulated both at the level of
      synthesis and degradation, our laboratory is investigating the role of
      phosphodiesterases (PDE) in the control of cAMP levels of oocytes. Using
      pharmacological and molecular tools, we have determined that a PDE3 is the enzyme
      involved in the control of cAMP levels in the oocytes. In vitro and in vivo
      studies have established that inhibition of the oocyte PDE3 blocks resumption of
      a PDE is per se sufficient to cause resumption of meiosis in an amphibian oocyte
      model. The pathways regulating this PDE isoform expressed in the oocyte is under
      investigation, as they may uncover the physiological signals controlling meiosis.

PMID- 9922094
TI  - The roles of steroidogenic factor 1 in endocrine development and function.
AB  - The orphan nuclear receptor steroidogenic factor 1 (SF-1) was initially isolated
      as a key regulator of the cytochrome P450 steroid hydroxylases in adrenocortical
      and gonadal cells. Subsequent analyses of SF-1 knockout mice have expanded
      considerably our understanding of the roles that SF-1 plays in endocrine
      development. These SF-1 knockout mice lacked adrenal glands and gonads, with
      consequent male-to-female sex reversal of their internal and external genitalia.
      Thus, SF-1 is essential for the embryonic survival of the primary steroidogenic
      organs. They further exhibited impaired gonadotrope function and agenesis of the
      ventromedial hypothalamic nucleus, establishing that SF-1 contributes to
      reproductive function at all three levels of the hypothalamic-pituitary-gonadal
      axis. This report reviews experiments that have defined these critical roles of
      SF-1 in endocrine development, and highlights areas of ongoing investigation.

PMID- 9922095
TI  - Intracellular mechanisms of ovarian cell apoptosis.
AB  - Apoptosis is an active cell 'suicide' essential for the elimination of
      superfluous cells during diverse physiological processes in essentially all
      animal species. Although regulation of apoptosis by extracellular mediators is
      cell type-specific, new insights based on characterization of conserved
      intracellular effectors have suggested that intracellular pathways leading to
      apoptosis in diverse organisms is regulated by a group of evolutionarily
      conserved genes including ced-9/Bcl-2, ced-4/Apaf-1 and ced3/caspases gene
      families. To study whether the Bcl-2 family proteins are important in the
      regulation of ovarian cell apoptosis, we have used transgenic mice and yeast 2
      hybrid protein protein interaction assay to characterize the roles of Bcl-2
      family proteins in ovarian atresia. The use of 2-hybrid analysis resulted in the
      isolation of a novel pro-apoptotic Bcl-2 protein, Bcl-2-related ovarian killer
      (Bok) and the identification of upstream mediators for ovarian cell apoptosis.

PMID- 9922096
TI  - The molecular basis of oocyte growth and development.
AB  - The mammalian oocyte is formed early in foetal life and may remain suspended at
      diplotene of the first meiotic prophase until several decades later. When,
      following follicular recruitment, the oocyte enters a growth phase where it
      increases in volume, and undergoes replication and redistribution of the
      cytoplasmic organelles. These modifications, including secretion of the zona
      pellucida, reflect a period of intensive RNA synthesis as the oocyte grows and
      accumulates the molecular program for embryogenesis. Throughout oocyte
      development follicle cell support is fundamental to provide the germ line cell
      with nutrients and growth regulators to ensure progression through the protracted
      growth phase. Conversely, the oocyte actively promotes growth and differentiation
      of the follicular cells. Finally, re-initiation of meiosis in mature oocytes
      results in the production of haploid gametes which are capable of supporting
      early embryo development. Our present knowledge of the molecular biology of
      mammalian oogenesis is discussed in this review.

PMID- 9922097
TI  - Unveiling the mechanism of action and regulation of the steroidogenic acute
      regulatory protein.
AB  - Stimulation of steroid-producing cells of the gonads and adrenals with trophic
      hormone (LH, and ACTH, respectively) produces a marked increase in steroid
      hormone synthesis within minutes. The rate-limiting step in this acute
      steroidogenic response is the transport of cholesterol from the outer to the
      inner mitochondrial membrane, where the first committed step in steroid synthesis
      is performed by the side-chain cleavage enzyme system (P450scc), resulting in the
      production of pregnenolone. This process of cholesterol translocation is blocked
      by inhibitors of protein synthesis (i.e. cycloheximide) indicating that the
      effect of trophic hormones, acting through the intermediacy of cAMP, most likely
      involves the de novo synthesis of a protein that is rapidly inactivated. The
      recently identified steroidogenic acute regulatory protein (StAR) appears to be
      the most likely candidate for the labile protein: (1) StAR is synthesized in
      response to cAMP and the StAR preprotein disappears rapidly in the presence of
      inhibitors of protein synthesis; (2) StAR has an N-terminal targeting sequence
      that directs the protein to the mitochondria; and (3) StAR protein is expressed
      almost exclusively in steroid-producing cells, its presence is correlated with
      steroid hormone production, and lack of functional StAR causes the autosomal
      recessive disease congenital lipoid adrenal hyperplasia (lipoid CAH),
      characterized by markedly impaired gonadal and adrenal steroid hormone synthesis.
      We have demonstrated that StAR is a target for serine phosphorylation mediated by
      protein kinase A (PKA), a process that is essential to maximizing StAR activity.
      StAR import by mitochondria is not essential to its steroidogenesis enhancing
      activity, and more likely, represents a means of rapidly inactivating StAR.
      Truncation mutations and site-directed mutations in StAR demonstrated that the C
      terminus of the protein contains the functionally important domains. Further, we
      have demonstrated potent steroidogenic activity of recombinant StAR protein on
      isolated mitochondria from bovine corpus luteum using protein that lacks the
      mitochondrial targeting sequence. These observations confirm that StAR import is
      not essential for its steroidogenic activity and suggest that StAR acts directly
      on the outer mitochondrial membrane in the absence of intermediary cytosolic
      factors. More recently, we have found that StAR functions as a cholesterol
      transfer protein that does not require a protein receptor or co-factor,
      suggesting that StAR acts directly on lipids of the outer mitochondrial membrane
      to promote cholesterol translocation.

PMID- 9922098
TI  - Molecular mechanisms of ovulation and luteinization.
AB  - Ovulation is a complex process initiated by the mid-cycle surge of luteinizing
      hormone (LH). Once initiated, a cascade of events occurs that culminates in the
      release of a fertilizable oocyte. The complex series of events involves specific
      ovarian cell types, diverse signaling pathways and temporally controlled
      expression of specific genes. This review will focus on several genes shown to
      control the ovulation process.

PMID- 9922099
TI  - Genetic mutations resulting in estrogen insufficiency in the male.
AB  - The biosynthesis of estrogens is catalyzed by an enzyme known as aromatase
      (aromatase cytochrome P450; P450 arom; the product of the CYP19 gene). In recent
      years a number of patients have been described suffering from aromatase
      deficiency due to mutations in the CYP19 gene, resulting in the synthesis of a
      non-functional gene product and a resulting failure to synthesize estrogens.
      Males with this condition have sustained linear growth into adulthood resulting
      from failure of epiphyseal closure. Osteopenia and reduced bone mineral density
      and bone age are also characteristic. Lack of circulating estrogens is
      accompanied by elevated testosterone and gonadotropins. One of the men had
      macroorchidism with testicular volumes in excess of 25 ml (Morishima et al. J.
      Clin. Endocrinol. Metab. 80, 3689, 1995). Semen analysis was not performed on
      this patient, but it is of note that the one patient described with estrogen
      insensitivity due to a mutation in the estrogen receptor had a normal sperm
      count, although motility was decreased (Smith et al., New England J. Med. 331.
      1056, 1994). By contrast, the other man with aromatase deficiency had testicular
      volumes of only 8 ml per testes, and was infertile. Sperm analysis revealed a
      count of 1 million/ml with 100% immotile sperm (Carani et al. New England J. Med.
      337, 91, 1997). However, his clinical picture is confused by the fact that
      another male sibling has azoospermia, but has no CYP19 mutation, suggesting that
      the infertility problem may be due to a second genetic condition in this
      consanguineous family. Recently mice have been generated in which the aromatase
      (CYP19) gene and the gene encoding the estrogen receptor-alpha have been
      inactivated by targeted disruption (ArKO and ERKO mice, respectively). Male ERKO
      mice are infertile with atrophy of the testes and seminiferous tubule
      dysmorphogenesis resulting in decreased spermatogenesis and inacive sperm. By
      contrast the ArKO mice are initially fertile and sire litters of normal size ad
      frequency, however with advancing age the number of litters sired decreases
      relative to those of wild type litter ates. In contrast to the ERKO mice, light
      microscopic analysis of the testes of the ArKO mice reveals no gross
      morphological abnormalties and the testes are of normal size. Following recent
      observations that the estrogen receptor-beta isoform is highly expressed in
      seminiferous epthelium, spermatids and spermatocytes, it is conceivable that the
      relatively high levels of estrogens present in the ERKO mice can act through the
      ER-beta to cause infertility by a direct action on the testes. In this context it
      is well known that administration of high levels of estrogen to men results in
      infertility. It is apparent that studies of human and mouse models with
      disruptions of aromatase and the estrogen receptor have as yet failed to clarify
      the role of estrogens in male fertility and testicular function. Development of
      an ER-beta knockout mouse, or else a double, or even triple, knockout model, may
      be required in order to resolve these issues.

PMID- 9922100
TI  - Estrogen receptor mutations.
AB  - The purpose of this paper is to review potential novel functional pathways by
      which estradiol and estrogenic compounds elicit biological responses in mammals.
      We will limit our approach to those novel functions suggested by phenotypes
      associated with estrogen receptor-alpha (ER alpha) gene mutations and
      polymorphisms. The study of these pathways has been greatly aided by the
      availability of ER alpha-minus mice, which lack classic biological responses to
      estradiol. In addition, the availability of an ER alpha-minus human family,
      aromatase-minus human families, and in the near future an aromatase-minus mouse
      model will allow correlations of novel phenotypes with the lack of active ER
      alpha protein. The ER alpha-minus mice can potentially be used to characterize in
      depth novel clinical phenotypes that link the functions of estrogens with sexual
      maturation, cardiovascular disease, osteoporosis, diabetes, and cancer.

PMID- 9922101
TI  - Developmental and endocrine aspects of normal ovarian aging.
AB  - Supplies of follicles are established during early fetal life and decrease
      exponentially thereafter by a process called atresia. Subfertility only starts at
      a mean age of about 30-31 years, when the remaining follicle reserve has become a
      fraction of its original number. Thereafter, a further decrease in both oocyte
      quantity and quality dictates the subsequent reproductive events including
      decrease of fertility, increased abortion rate, the end of fertility, the
      beginning of cycle irregularity and, when almost no follicles are left, the
      occurrence of menopause. The same remarkable variation of age at menopause almost
      certainly is also present for the preceding reproductive events. When quantity
      and quality of antral follicles drop below a critical threshold, there is a
      subsequent drop in inhibine B resulting in the selective FSH rise at a mean age
      of 37-38 years. This FSH rise explains the accelerated follicle depletion, the
      increased proportion of growing follicles reaching the selectable stage, the
      shortening of the follicular phase and the increased incidence of dizygotic
      twinning. The concurring decrease of oocyte quality is in line with the increased
      incidence of abortions and chromosomal aberrations after age 35.

PMID- 9922102
TI  - Genes and premature ovarian failure.
AB  - Premature ovarian failure (POF) is an heterogeneous syndrome. Among genetic
      causes, X monosomy as in Turner syndrome or X deletions and translocations are
      known to be responsible for POF. The genes involved in ovarian function, located
      on the X chromosome are still unknown. On the other hand, autosomal abnormalities
      have been identified in POF patients such as mutations of the FSH gene, the LH
      and FSH receptor genes, chromosome 3q containing the blepharophimosis gene, the
      ATM gene (Ataxia-telangiectasia gene). Mutations in the AIRE gene (responsible
      for APECED syndrome) can involve ovarian insufficiency. It is likely that studies
      on the function of the protein AIRE might improve our knowledge on follicular
      development. Furthermore, different mouse models of ovarian failure such as mouse
      lacking connexins or mice lacking GDF9 (growth derived factor 9), might increase
      our knowledge of ovarian failure. In the future, a better knowledge of the
      cellular and biochemical components involved in folliculogenesis and apoptosis
      should elucidate the mechanisms of POF.

PMID- 9922103
TI  - The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular
      fate.
AB  - Molecular geneticists and ovarian physiologists today face the challenge of
      defining and reconciling two major biological imperatives that each center on
      oogenesis, folliculogenesis and competition between ovarian follicles: (1),
      defining how the mitochondrial genome--important in both aging and a number of
      serious mitochondrial diseases--is refreshed and purified as it passes, via the
      oocyte's cytoplasm, from one generation to the next; and (2), endeavouring to
      discover what cytoplasmic factor(s) it is that permits some eggs but not others
      to produce viable embryos and ongoing pregnancies. We review here in detail the
      passage of mitochondria through the female germ cell line. For mitochondria, the
      processes of oogenesis, follicle formation and loss constitute a
      restriction/amplification/constraint event of the kind predicted by L. Chao for
      purification and refinement of a haploid genome. We argue that maintaining the
      integrity of mitochondrial inheritance is such a strong evolutionary imperative
      that we should expect at least some features of ovarian follicular formation,
      function and loss to be primarily adapted to this specific purpose. We predict,
      moreover, that to prevent accumulation of mild mitochondrial genomes in the
      population there is a need for physiological female sterility prior to total
      depletion of ovarian oocytes, a phenomenon for which there is empirical evidence
      and which we term the oopause.

PMID- 9922104
TI  - Follicle selection in sheep with breed differences in ovulation rate.
AB  - Genetic variations in ovulation rates which occur in different breeds of sheep
      provide useful models to explore the mechanisms underlying the antral of follicle
      development. Two principal strategies have evolved which enable these high
      fecundity breeds to over-ride the mechanisms which drastically restrict the
      number of ovulatory follicles. Firstly, Finnish Landrace involves reducing the
      sensitivity of the hypothalamic-pituitary unit to the feedback effects of ovarian
      hormones (inhibin and/or oestradiol) which normally suppress FSH. Treatment with
      oestrogens or immunisation against oestradiol or inhibin are pharmacological
      methods of manipulating the feedback system. The second mechanism as exemplified
      by the FecB gene results in an increased ovulation rate associated with the
      'precocious' development of a large number of small antral follicles. The gene
      mutation responsible for this effect has not yet been identified. It is likely
      that the product will be a factor which enhances follicular development as well
      as affecting gonadotrophic function. Identification of the gene product should
      permit further research into the factors which regulate the orderly development
      of follicles within the ovary.

PMID- 9922105
TI  - The endocrinology of dizygotic twinning in the human.
AB  - Heredity, higher maternal age and increased parity are well defined conditions
      associated with dizygotic twinning. An endocrine model of excessive secretion of
      pituitary gonadotrophic hormones explains multiple ovulation as a result of
      multiple follicle growth. In hereditary conditions FSH levels are indeed clearly
      elevated because of increase in stimulating mechanisms that regulate pituitary
      gonadotropin secretion while in most non-hereditary conditions, overshoot FSH
      secretions occurs as a result of diminished ovarian feedback. Puberty is a
      condition in which the hypothalamic LHRH pulse generator is reinitiated and this
      is typically characterized by temporary overshoot LH and FSH secretion, probably
      due to not yet fully operational ovarian feedback. In adult females situations
      can be found that mimic this peripubertal event such as while recovering from
      hypothalamic amenorrhea. Under these circumstances more DZ twinning can be
      observed. Elevated FSH levels along with ageing in premenopausal women probably
      underlie the age related increased risk of dizygotic twinning. The apparent
      paradox in the combination of age related decline in fecundity and rise in
      twinning risk can be explained by incidental presence in the cohort of more than
      one follicle, containing vital oocytes under deficient feedback mechanisms that
      lead to high FSH.

PMID- 9922106
TI  - Insulin resistance in polycystic ovary syndrome: treating a phenotype without a
      genotype.
AB  - PCOS women are uniquely insulin resistant. The underlying genetic defect in
      insulin action is unknown. Obesity aggravates the underlying predisposition to
      insulin resistance. Diagnostic criteria which focus on menstrual irregularity are
      more likely to identify insulin resistant women. About 40% of PCOS women display
      glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in
      response to an oral glucose challenge. The lack of a clear etiologic mechanism to
      the syndrome has led to a multitude of symptom-oriented treatments with few
      therapies improving all aspects of the endocrine syndrome of PCOS. Empirical
      studies of interventions improving insulin sensitivity in PCOS, either weight
      loss/diet programs or pharmaceutical agents, have been shown to improve the
      endocrine abnormalities in the syndrome. These initial results with anti-diabetic
      agents, though promising, need to be confirmed in larger, randomized studies.

PMID- 9922107
TI  - Role of cytochrome P450c17 in polycystic ovary syndrome.
AB  - The hyperandrogenism of polycystic ovary syndrome (PCOS) appears to be due to
      dysregulation of steroidogenesis within the ovaries and adrenal glands. P450c17
      is the key enzyme that regulates androgen synthesis. It is the only enzyme known
      to have the capacity to convert C21-precursors to the androgen pre-hormones, the
      17-ketosteroids. It is a single enzyme with two activities, 17-hydroxylase and
      17,20-lyase. Thus, its regulation is a significant factor in the expression of
      hyperandrogenism. Androgen secretion is LH-dependent in the ovary and ACTH
      dependent in the adrenal glands. The androgenic response to each of these tropic
      hormones seems to be modulated by intra-ovarian or intra-adrenal autocrine and
      paracrine mechanisms. This modulation serves to regulate steroid hormone
      secretion in tissue-specific ways. Insulin, IGFs and inhibin are among the many
      growth factors capable of augmenting the response to LH and ACTH. The insulin/IGF
      system stimulates P450c17 mRNA expression and activities in the ovaries and
      adrenal glands. An integrating link between insulin resistance and
      hyperandrogenemia may be serine phosphorylation, which inhibits activity of the
      insulin receptor and promotes the 17,20-lyase activity of P450c17. However, it
      must be kept in mind that there is some evidence for the existence of P450c17
      independent pathways of androgen biosynthesis.

PMID- 9922108
TI  - Genetics of polycystic ovary syndrome.
AB  - We have found evidence for the involvement of two major genes in the aetiology of
      PCOS. The results of both linkage and association studies suggest that CYP11a
      (coding for P450 cholesterol side chain cleavage) and the insulin VNTR regulatory
      polymorphism are important genes in the aetiology of PCOS and may explain, in
      part, the heterogeneity of the syndrome. Differences in expression of CYP11a
      could account for variation in androgen production in women who have polycystic
      ovaries and those subjects who are homozygous for III alleles at the insulin gene
      VNTR locus are more likely to be hyperinsulinaemic. It is likely that other genes
      are involved in the aetiology of PCOS. Recent results lend weight to the idea
      that PCOS represents a complex trait in which several genes--but perhaps a
      relatively small number of key genes--contribute, in conjunction with nutritional
      factors, to the observed clinical and biochemical heterogeneity.

PMID- 9922110
TI  - Activating and inactivating mutations in LH receptors.
AB  - The glycoprotein hormones luteinizing hormone (LH) and human chorionic
      gonadotropin (hCG), both of which act through the LH receptor, play an important
      role in the regulation of both male and female gonadal function. Testicular
      androgen production by the Leydig cells is almost entirely dependent on LH/hCG
      action, while in the ovary LH triggers both oestrogen and progestin secretion and
      ovulation of the Graaffian follicles. In this review we discuss the various
      mutations that have been found in the LH receptor gene in the human and the
      lessons that can be learned from the phenotypes of the carriers of these
      mutations.

PMID- 9922109
TI  - Inactivating FSH receptor mutations and gonadal dysfunction.
AB  - A variety of mutations and polymorphisms of genes regulating female and male
      reproductive functions have been discovered during the last few years. These
      include several inactivating and activating mutations in LH receptor genes. The
      first mutation of FSH receptor (FSHR) gene was discovered in six Finnish
      families. This inactivating Ala189Val transition in the extracellular receptor
      domain causes primary amenorrhea, arrest of follicular development and
      infertility in homozygous women. In contrast to females, this mutation did not
      cause absolute infertility in males but only suppressed spermatogenesis. Another
      inactivating mutation of the FSHR gene has been found at position 191 (Asn191Ile)
      in a healthy fertile woman. The studies on inactivating FSHR mutations
      demonstrate that normal ovarian function is critically dependent on FSH while, in
      contrast to earlier views, male fertility is less strictly dependent on normal
      FSH action.

PMID- 9922111
TI  - Genetics of male infertility.

PMID- 9922112
TI  - Endocrine aspects of ageing in the male.
AB  - There is a statistical decline of testosterone levels in ageing men, most
      manifest in free testosterone. While this fall is only moderate, ageing men show
      clinical signs of hypogonadism (loss of muscle mass/strength, reduction in bone
      mass and an increase in visceral fat). This might represent not only a fall but
      (also) an impairment of the biological action of androgens in target organs. The
      first small scale studies of androgen supplement administration in ageing men
      were not disappointing. Anticipated risks lie with the prostate and the
      cardiovascular system. The risks with regard to prostate disease are often over
      rated. The question remains how the segment of the ageing male population
      possibly benefiting from androgen supplements, can be identified. For the
      treatment of postmenopausal women 'designer oestrogens' are being developed;
      similarly, designer androgens retaining beneficial anabolic effects with
      elimination of harmful effects on the prostate and cardiovascular system, could
      be devised.

PMID- 9922113
TI  - Knockout mouse model and gametogenic failure.
AB  - To evaluate the function of a defined gene in gametogenesis, exciting
      opportunities are offered by the introduction of techniques to generate knockout
      mice. In this short article, we briefly describe a few gene knockout mouse
      models, which show a phenotype that involves impairment of gametogenesis and/or
      fertility. The focus will be on the mHR6B gene knockout mouse, which shows male
      infertility. The mHR6B gene encodes an ubiquitin-conjugating enzyme, and the data
      point to an important role of the ubiquitin pathway in gametogenesis.

PMID- 9922114
TI  - Transgenic mouse models for gonadal tumorigenesis.
AB  - The versatile transgenic (TG) techniques allow the production of in vivo animal
      models for a variety of diseases, including malignant tumors, through tissue
      specific expression of oncogenes. We have created a TG mouse model for gonadal
      somatic cell tumors by expressing the powerful viral oncogene, Simian virus 40 T
      antigen (Tag) under regulation of the murine inhibin alpha-subunit promoter (inh
      alpha). Ovarian granulosa and theca cell tumors were formed in the female, and
      those of testicular Leydig cells, in the male TG mice at the age of 5-6 months,
      with 100% penetrance. The tumors produced high levels of inhibin peptides,
      especially the alpha-subunit, and were steroidogenically active, mainly producing
      progesterone. The gonadal tumorigenesis was gonadotropin-dependent, since TG mice
      rendered gonadotropin-deficient by crossbreeding them into the hypogonadotropic
      hpg genetic background, or by treating them with a gonadotropin-releasing hormone
      (GnRH) antagonist, did not develop tumors. In order to study the possibility of
      using the tumor mouse model for testing gene therapy, we created another TG mouse
      model expressing under the same inhibin-alpha promoter the Herpes Simplex virus
      (HSV) thymidine kinase (TK) transgene. The inh alpha/HSV-TK mice were crossbred
      with the inh alpha/Tag mice and the double mutant mice also developed gonadal
      tumors. When they were treated with antiherpes drugs (acyclovir or gancyclovir),
      further growth of the tumors was blocked. These preliminary findings prove the
      principle that tumor ablation in our TG mouse model can be achieved by
      transduction of the HSV-TK gene into the tumor cells. Besides studies of
      formation, regulation and therapy of the tumors in vivo, immortalized cell lines
      derived from them provide models for studies of gonadal somatic cell functions in
      vitro.

PMID- 9922115
TI  - Age-related changes in the inner zone of the adrenal cortex of the rat--a
      morphologic and biochemical study.
AB  - In this work, a correlative morphologic and biochemical study on the effects of
      ageing on the rat adrenal Inner Zone (IZ) was made. Male Wistar rats were studied
      at 2, 6, 12, 18 and 24 months. Structural data of Zona Fasciculata (ZF) showed
      age-related increase in cell volume (P < 0.05), decrease in mitochondria (P <
      0.01) and smooth endoplasmic reticulum (SER) volumes, and increase in lipid
      droplets (P < 0.01) and lipofuscin granules (P < 0.01) volumes. In Zona
      Reticularis, the main change observed was the increase in lipofuscin granules (P
      < 0.001). Serum corticosterone from unstimulated rats increased until 12 months
      but decreased thereafter (P < 0.01), to levels below those from 2-month-old rats.
      Similarly, plasma adrenocorticotrophic hormone (ACTH) presented a maximum at 12
      months, followed by a decrease to levels higher than at 2 months (P < 0.05). In
      rats injected either with only ACTH or dexamethasone, before ACTH stimulation,
      corticosterone level had a maximum at 12 months. In aged rats, serum high density
      lipoprotein (HDL) and adrenal cholesterol ester increased significantly (P < 0.05
      and P < 0.01, respectively), whereas adrenal corticosterone decreased. Products
      of lipid peroxidation, assayed with the thiobarbituric acid reaction and
      fluorimetry showed an age-related increase (P < 0.05). The age-related decrease
      in mitochondria and SER volumes is consistent with the decrease of serum
      corticosterone. The increase in lipid droplet and HDL and the reduction of
      adrenal corticosterone level correlate with the increase of adrenal cholesterol
      ester content. These suggest a continued uptake of steroid precursor but a
      reduced steroid synthesis. On the whole, the data provide evidence for an age
      related reduced functional ability of IZ and particularly of ZF.

PMID- 9922116
TI  - Changes in integrin/adhesion molecule expression, but not in the T-cell receptor
      repertoire, in old mice infected with tuberculosis.
AB  - The results of this study present data in support of the hypothesis that T
      lymphocytes in both young and old mice infected with virulent Mycobacterium
      tuberculosis undergo changes in expression of cell surface integrin/adhesion
      molecules as determined by flow cytometric analysis. These data thus further
      support the hypothesis that a reduced ability of T-cells in old mice to
      adequately and promptly accumulate at sites of inflammation induced by bacterial
      implantation is a central parameter underlying the increased susceptibility of
      these mice to this intracellular bacterial infection. In addition, however, no
      changes were observed in terms of the T-cell receptor expression (repertoire) of
      these animals, indicating that this facet of immunity is preserved in aging.

PMID- 9922117
TI  - The effects of aging and calorie restriction on plasma nutrient levels in male
      and female Emory mice.
AB  - We examined the effect of diet, age (4.5, 13 and 23 months), and sex on plasma
      levels of retinol, tocopherol, ascorbate, cholesterol, glucose and
      glycohemoglobin in male and female Emory mice which were fed control (C) and 50%
      calorie restricted (R) diets. Results showed that C fed animals tended to have
      higher levels of plasma ascorbate (50-71%), cholesterol (23-71%), glucose (38
      81%) and glycohemoglobin (50%). However, these diet differences varied with the
      age and sex of the animals. Plasma retinol levels were lower only in R males vs.
      C males (50%). Novel sex-related differences in levels of plasma retinol (2-fold
      higher in C male mice than in C or R female mice) are described. Aging was
      associated with trends towards lower levels of plasma ascorbate (14-25%), glucose
      (34-36%) and glycohemoglobin (47-57%) from 4.5 to 23 months of age. However,
      these age differences depended upon the diet and sex of the animals. These data
      suggest that lower plasma levels of glucose, glycosylated hemoglobin and
      cholesterol may be causally related to the life extension noted in R animals
      since elevated levels of these moieties have been related to aging. Since
      oxidative stress is thought to be causally related to aging it appears unlikely
      that retinol, tocopherol and ascorbate are causally related to R-induced life
      extension.

PMID- 9922118
TI  - Primmorphs generated from dissociated cells of the sponge Suberites domuncula: a
      model system for studies of cell proliferation and cell death.
AB  - Sponges (Porifera) represent the lowest metazoan phylum; they have been shown to
      be provided with the characteristic metazoan structural and functional molecules.
      One autapomorphic character of sponges is the presence of high levels of
      telomerase activity in all cells (or almost all cells, including somatic cells).
      In spite of this fact previous attempts to cultivate sponge cells remained
      unsuccessful. It was found that dissociated sponge cells do not replicate DNA and
      lose their telomerase activity. In addition, no nutrients or metabolites have
      been detected that would stimulate sponge cells to divide. In the present study
      we report the culture conditions required for the formation of multicellular
      aggregates from dissociated single cells of Suberites domuncula, termed
      primmorphs. These primmorphs are formed in seawater without addition of further
      supplements, and have an organised tissue-like structure; they have been cultured
      for more than 5 months. Cross-sections revealed a distinct external layer covered
      by a continuous pinacoderm, and a central zone composed primarily of spherulous
      cells. After their association into primmorphs, the cells turn from the
      telomerase-negative state into the telomerase-positive state; a telomerase level
      of 4.7 total product generated (TPG) units/5 x 10(3) cell equivalents has been
      determined. Moreover, a major fraction of the cells in the primmorphs undergoes
      DNA synthesis and hence has the capacity to grow. Applying the BrdU-labelling and
      detection assay it is demonstrated that up to 33.8% of the cells in the
      primmorphs are labelled with BrdU after an incubation period of 12 h. It is
      proposed that the primmorph system described here is a powerful novel model
      system to study basic mechanisms of cell proliferation and cell interaction, as
      well as of morphogenesis, ageing and apoptosis.

PMID- 9922119
TI  - The life-shortening effect of reduced physical activity is abolished by a fat
      rich diet.
AB  - In female mice on a control diet (3.6% fat) reduced physical activity leads to a
      reduction of the average life span. So the average age at death of an inactive
      group is 500 +/- 166 compared to 565 +/- 175 days in an active control group. If
      the animals are kept on a fat rich diet (12.4% fat) this effect of physical
      activity restriction is no longer observable and the average age at death is 570
      +/- 142 days, within the range of the control animals. The increased fat intake
      seems to reduce the stress or to increase the resistance to stress in the
      activity restricted animals. So stress is a crucial determinant of life span.

PMID- 9922121
TI  - Biological ages of adult men and women with Down's syndrome and its changes with
      aging.
AB  - In order to examine to what extent a gene dysregulation such as Down's syndrome
      (DS) causes the advance of global biological aging as well as segmental progeroid
      syndrome, 8 years of longitudinal data were gathered on 14 hematology and blood
      chemistry characteristics of five adult men and six adult women with DS and four
      adult men with cerebral palsy (CP). Biological age (BA) was established through
      the application of principal component analysis based on the data for the same 14
      variables of 436 healthy adult men. The BAs of five adult men and six adult women
      with DS, and four adult men with CP were estimated by using the equation
      calculated from healthy adult men data, and the BAs were compared. The result of
      this study indicated that: (1) a genetic condition such as Down's syndrome causes
      not only segmental progeroid syndrome but also premature aging accompanying
      global senescence in various organ levels; (2) premature aging exhibited by adult
      men and women with DS justifies the evidence of primary aging; and (3) the rate
      of aging for BA in DS patients is nearly a twofold increase as compared to
      healthy subjects.

PMID- 9922120
TI  - Age dependent decline in the 3'-->5' exonuclease activity involved in
      proofreading during DNA synthesis.
AB  - A 3'-->5' exonuclease found in rat liver excises mispaired nucleotides at the 3'
      hydroxyl end of primer chains such as poly dA-d(T9-C). Consequently, the priming
      activity of the chain from which the mispaired base was cut is greatly increased
      during DNA synthesis. These results suggest that the 3'-->5' exonuclease acts as
      a proofreading enzyme during DNA synthesis. The activity of this 3'-->5'
      exonuclease in the liver of 24-month-old rats is approximately 30% lower than the
      activity found in 4-month-old rats. Furthermore, non-complementary nucleotide
      incorporations by DNA polymerases from aged rats are observed during DNA
      synthesis on poly dA-dT10. The number of misincorporations decreases in the
      presence of the 3'-->5' exonuclease, but not all errors are prevented even when
      DNA polymerase and 3'-->5' exonuclease are added at an activity ratio similar to
      that found in vivo. The data suggest that declines in both the fidelity of DNA
      polymerase and the 3'-->5' exonuclease activity related to proofreading during
      the aging process lead to a higher frequency of base misincorporations during DNA
      replication.

PMID- 9922122
TI  - Expressional changes in alternative splicing affecting genes during cell passage
      of human diploid fibroblasts.
AB  - Normal human diploid cells have a limited proliferative lifespan in in vitro
      cultures. Changes in gene expression have been examined for understanding control
      mechanisms of limited proliferative lifespan. and enhanced expression of growth
      suppressing genes such as p21 was reported in late-passaged cells. We screened
      genes which were expressed preferentially in mid-passaged cells by the
      differential plaque screening of the subtracted cDNA libraries prepared from
      young, life-extended, and immortalized SV40-transformed human fibroblasts. Among
      isolated clones, ASF/SF2, which was known to affect alternative splicing, was
      expressed in normal fibroblasts with a peak at mid-passage. Relative expression
      levels of SC35 and hnRNPA1, which are also known to affect alternative splicing,
      was also highest at mid-passage. Changes in alternative splicing at mid-passage,
      if it occurred, may play a crucial role in the process of cellular senescence.

PMID- 9922123
TI  - Phosphorylation and coupling of zeta-chains to activated T-cell receptor
      (TCR)/CD3 complexes from peripheral blood T-cells of elderly humans.
AB  - Aging is often accompanied by altered T-cell signaling and functions. Signals
      mediated through the T-cell receptor (TCR)/CD3 complex are associated with
      tyrosine phosphorylations of zeta-chains by the regulated activities of protein
      tyrosine kinases p56(lck) and p59(fyn) as well as protein tyrosine phosphatases.
      In the present investigation, the coupling and phosphorylation of zeta-chains to
      TCR/CD3 immunocomplexes were examined in peripheral blood T-cells from 13 elderly
      and young humans stimulated by ligation of the TCR/CD3 with cross-linked anti
      CD3epsilon monoclonal antibody OKT3. Western blots analyzing the non-covalent
      coupling of zeta-chains to TCR/CD3 immunocomplexes from Brij-96 detergent lysates
      of anti-CD3 ligated T-cells showed that the levels of zeta-chains within TCR/CD3
      immunocomplexes from T-cells of elderly and young subjects did not significantly
      differ. By contrast, the levels of phosphorylated zeta-chains generated during in
      vitro phosphorylations of TCR/CD3 immunocomplexes from elderly subjects were
      significantly reduced and averaged 44% of those observed for anti-CD3epsilon
      ligated T-cells from young subjects. Analyses of the levels of zeta-chain
      coupling and phosphorylations in T-cells from each of the 13 elderly individuals
      also showed that the reductions in zeta-chain phosphorylations were heterogeneous
      and unrelated to modest reductions in coupling. Furthermore, the age-related
      decreases in zeta-chain phosphorylations were not due to diminished frequencies
      of CD3epsilon+ cells or densities of CD3epsilon surface receptors and could be
      observed without reductions in epsilon-chain phosphorylations. These results
      suggest that aberrancies of zeta-chain phosphorylations can occur in T-cells of
      elderly humans independent from any uncoupling of zeta-chains to activated
      TCR/CD3 complexes.

PMID- 9922124
TI  - Premature induction of aging in sublethally H2O2-treated young MRC5 fibroblasts
      correlates with increased glutathione peroxidase levels and resistance to DNA
      breakage.
AB  - Human MRC5 fibroblasts, at different passages in cultures, were used as an in
      vitro model to assess variations and/or induction of aging parameters under basal
      conditions or following sublethal oxidative stress by H2O2. DNA sensitivities to
      oxidatively-induced breakage, rather than basal levels of damaged DNA, were
      significantly different between cultures at low and high population doubling
      level (PDL): old cells maintained most of their DNA integrity even at high
      concentrations of H2O2, while young cells showed more extensive DNA damage which
      developed in a dose-dependent fashion. However, young cells pretreated with low
      doses of H2O2 exhibited increased resistance against further oxidative damage to
      DNA thus reproducing a senescent-like profile of sensitivity. In turn, DNA from
      old cultures incubated in a NAD precursor-free medium was more prone to H2O2
      induced strand breaks mimicking DNA sensitivity of young cells. The extent of
      oxidatively-induced DNA damage in MRC5 populations correlated inversely with the
      levels of glutathione peroxidase (GPx) activity that almost doubled when cells
      passed from the young to the senescent stage. In addition, H2O2-pretreatment of
      young cells induced an increase in GPx expression approaching old cell values and
      promoted also the premature appearance of neutral beta-galactosidase activity and
      decreased c-fos expression upon serum stimulation, both of which were assumed to
      be characteristic traits of the senescent phenotype.

PMID- 9922125
TI  - Changes in the expression of protein kinase C (PKC), phospholipases C (PLC) and D
      (PLD) isoforms in spleen, brain and kidney of the aged rat: RT-PCR and Western
      blot analysis.
AB  - The age-dependent changes of expression of protein kinase C (PKC), phospholipase
      C (PLC) and phospholipase D (PLD) isozymes were analyzed in spleen, brain and
      kidney of young-adult (12-16 week-old) and aged (82-88 week-old) rats. The
      activities of spleen cPKC and nPKC were significantly decreased by nearly 35 and
      30% in aged rats compared to those of young adults, respectively (P < 0.05). The
      level of PKC beta1 was significantly decreased in aged rats as assessed by RT-PCR
      and Western blot analyses. In aged rat brain where the activity of cPKC was
      significantly decreased by nearly 25% (P < 0.05), PKC alpha and beta1 isozymes
      were significantly down-regulated. In kidney, the level of PKC beta2 was
      decreased. In spleen the both mRNA and protein levels of PLC beta2 and gamma2
      were significantly down-regulated in aged rat (P < 0.05). PLC beta1 was also
      significantly lower in aged rat brain (P < 0.05) as assessed by RT-PCR and
      Western blotting. Moreover, PLC beta1 was significantly down-regulated in both
      mRNA and protein levels in aged rat kidney (P < 0.05). In contrast, the tissues
      examined, the expressions of PLD isozymes (PLD1a, 1b and 2) were rather stable in
      the course of aging. These results indicate that mRNAs of PLD isozymes were
      rather stable but that particular PKC and PLC isozymes were down-regulated in
      different tissues during aging, suggesting age-dependent decline of specific PKC
      and PLC isozymes in organs which may, at least in part, be implicated in tissue
      dysfunction with aging.

PMID- 9922126
TI  - Age-related changes in septal serotonergic, GABAergic and glutamatergic
      facilitation of retention in SAMP8 mice.
AB  - SAMP8/TaJf(P8) mouse strain has an inherited age-related impairment of learning
      and memory with its onset relatively early in its lifespan. Previously, it was
      reported that cholinergic and glutamatergic drugs injected into the hippocampus
      after behavioral training showed considerable shifts in the dose that improved
      retention in mice at 12 compared to 4 months of age. Cholinergic neurons in the
      septum supply most of the acetylcholine released in the hippocampus. In the
      present study, we determined if altered functional status of neurotransmission in
      the septum might account for the decrease in cholinergic and glutamatergic
      activity in the hippocampus of older SAMP8 mice. After training on footshock
      avoidance, P8 mice received a drug injection into the septum. Retention was
      tested 1 week later. The results indicate that bicuculline, GABA-A, and saclofen,
      GABA-B, receptor antagonist had to be injected at a higher dose in 12- than in 4
      month-old mice to improve retention. The serotonergic antagonists, ketanserin and
      methiothepin, both showed dose response shifts such that less drug was needed to
      improve retention in 12- as compared to 4-month-old mice. It required four times
      more L-glutamate to improve retention in 12- than in 4-month-old mice. Agonists
      for acetylcholine, dopamine and norepinephrine receptors or an opiate antagonist
      required little or no change in the dose needed to improve retention in older P8
      mice. SAMP8 mice may show an age-related impairment of septohippocampal
      functioning.

PMID- 9922127
TI  - Early male initiation (time frame shift): a possible contributor to their
      shortened lifespan.
AB  - The shorter life expectancy of human males, as compared with females, was
      analyzed by utilizing the assumption that the specific rate of change of disease
      occurrence or mortality was a function of the specific rate of change of age.
      Separate plots were made of log incidence versus log age, for males and females.
      In several disorders, the line representing males was displaced toward the
      origin, as compared with the females. This 'time frame shift' suggested an
      earlier onset of the disorder or its precursors in males ('early male
      initiation'). While the physiologic/genetic basis for this has to be fully
      determined, the earlier male 'initiation' of disorders may be a contributing
      factor to their shorter life expectancy.

PMID- 9922128
TI  - Structure and function of the core histone N-termini: more than meets the eye.
AB  - For two decades, the core histone N-termini generally have been thought of as
      unstructured domains whose function is to bind to DNA and screen negative charge.
      New data indicates that both the molecular mechanisms of action and biological
      functions of the core histone N-termini in chromatin are considerably more
      complex. At the level of the chromatin fiber, multiple distinct functions of the
      N-termini are required to achieve higher order chromatin condensation, two of
      which apparently involve protein-protein rather than protein-DNA interactions. In
      addition, the N-termini have been documented to participate in specific
      interactions with many chromatin-associated regulatory proteins. Here, we discuss
      evidence supporting the new concepts that when functioning in their natural
      chromatin context, (1) the N-termini are engaged primarily in protein-protein
      interactions, (2) as a consequence of these interactions the N-termini adopt
      specific secondary structure, (3) posttranslational modifications such as
      acetylation disrupt the ability of the N-termini to form secondary structure, and
      (4) because the N-termini perform essential roles in both chromatin condensation
      and also bind specific chromatin-associated proteins, the global structure and
      function of any given region of the genome will be determined predominantly by
      the core histone N-termini and their specific interaction partners.

PMID- 9922129
TI  - Location of the membrane-docking face on the Ca2+-activated C2 domain of
      cytosolic phospholipase A2.
AB  - Docking of C2 domains to target membranes is initiated by the binding of multiple
      Ca2+ ions to a conserved array of residues imbedded within three otherwise
      variable Ca2+-binding loops. We have located the membrane-docking surface on the
      Ca2+-activated C2 domain of cPLA2 by engineering a single cysteine substitution
      at 16 different locations widely distributed across the domain surface, in each
      case generating a unique attachment site for a fluorescein probe. The
      environmental sensitivity of the fluorescein-labeled cysteines enabled
      identification of a localized region that is perturbed by Ca2+ binding and
      membrane docking. Ca2+ binding to the domain altered the emission intensity of
      six fluoresceins in the region containing the Ca2+-binding loops, indicating that
      Ca2+-triggered environmental changes are localized to this region. Similarly,
      membrane docking increased the protonation of six fluoresceins within the Ca2+
      binding loop region, indicating that these three loops also are directly involved
      in membrane docking. Furthermore, iodide quenching measurements revealed that
      membrane docking sequesters three fluorescein labeling positions, Phe35, Asn64,
      and Tyr96, from collisions with aqueous iodide ion. These sequestered residues
      are located within the identified membrane-docking region, one in each of the
      three Ca2+-binding loops. Finally, cysteine substitution alone was sufficient to
      dramatically reduce membrane affinity only at positions Phe35 and Tyr96,
      highlighting the importance of these two loop residues in membrane docking.
      Together, the results indicate that the membrane-docking surface of the C2 domain
      is localized to the same surface that cooperatively binds a pair of Ca2+ ions,
      and that the three Ca2+-binding loops themselves provide most or all of the
      membrane contacts. These and other results further support a general model for
      the membrane specificity of the C2 domain in which the variable Ca2+-binding
      loops provide headgroup recognition at a protein-membrane interface stabilized by
      multiple Ca2+ ions.

PMID- 9922131
TI  - Quaternary structure of V1 and F1 ATPase: significance of structural homologies
      and diversities.
AB  - The V1 ATPase from the tobacco hornworm Manduca sexta and the Escherichia coli F1
      ATPase were characterized by small-angle X-ray scattering (SAXS). The radii of
      gyration (Rg) of the complexes were 6.2 +/- 0.1 and 4.7 +/- 0.02 nm,
      respectively. The shape of the M. sexta V1 ATPase was determined ab initio from
      the scattering data showing six masses, presumed to be the A and B subunits,
      arranged in an alternating manner about a 3-fold axis. A seventh mass with a
      length of about 11.0 nm extends perpendicularly to the center of the hexameric
      unit. This central mass is presumed to be the stalk that connects V1 with the
      membrane domain (V(O)) in the intact V1V(O)-ATPase. In comparison, the shape of
      the F1 ATPase from E. coli possesses a quasi-3-fold symmetry over the major part
      of the enzyme. The overall asymmetry of the structure is given by a stem, assumed
      to include the central stalk subunits. The features of the V1 and F1 ATPase
      reveal structural homologies and diversities of the key components of the
      complexes.

PMID- 9922130
TI  - How fumarase recycles after the malate --> fumarate reaction. Insights into the
      reaction mechanism.
AB  - Recycling of yeast fumarase to permit repetition of its reaction chemistry
      requires two proton transfers and two conformational changes, in pathways that
      are different in detail but thematically similar in the two directions. In the
      malate --> fumarate direction, simple anions such as acetate accelerate the
      fumarate-off step producing E(H(f)), a fumarate-specific isoform that retains the
      C3R-proton of malate. Fumarate specificity is shown with S-2,3
      dicarboxyaziridine, which is competitive vs fumarate and noncompetitive with
      malate as substrate. The steady-state level of E(H(f)), based on Kii (S-2,3
      dicarboxyaziridine), is increased by D2O and decreased by imidazole acting as a
      general acid for conversion of E(H(f)) to E(H(f))H. E(H(f))H is fumarate-specific
      as shown by the inhibition pattern with ClO4-. The pKa of this step is
      approximately 7.25 based on the pH dependence of Kii (ClO4-). A conformational
      change occurs next as shown by high sensitivity of k(cat) but not k(cat)/Km, to
      the microviscosogen, glycerol, and change to a nonspecific isoform, E(H(mf))H,
      probably the same species formed in the fumarate --> malate direction from malate
      specific intermediates by a different conformational change. Malate enters the
      cycle by reaction with E(H(mf))H and returns to E(m)H x malate after a second
      conformational change. When fumarate-off is slow, as in low anion medium, malate
      itself becomes an activator of malate --> fumarate. This effect occurs with
      changes in inhibition patterns suggestive of the bypass of the slow E(f) -->
      E(mf) conversion in favor of direct formation of E(mf) when free fumarate is
      formed. 3-Nitro-2-hydroxypropionate, a strong inhibitor of fumarase [Porter, D.
      J. T., and Bright, H. J. (1980) J. Biol. Chem. 255, 4772-4780] in its carbanion
      form, is competitive with both malate and fumarate. Therefore, 3-nitro-2
      hydroxypropionic acid interacts with E(H(mf))H and not with E(m) or E(f)
      isoforms. Occurrence of two different conformational changes in the recycling
      process suggests that the reaction chemistry employs a two-step mechanism. The
      specificity of inhibition for E(H(mf))H is consistent with the expected
      intermediate of a carbanion mechanism, E(H)H x carbanion-. The proton transfers
      and conformational changes of recycling occur in the same sequence that is
      expected for this reaction chemistry. Several examples of ligand-activated
      conformational changes are reported.

PMID- 9922132
TI  - Crystal structure of L-arginine:inosamine-phosphate amidinotransferase StrB1 from
      Streptomyces griseus: an enzyme involved in streptomycin biosynthesis.
AB  - Inosamine-phosphate amidinotransferases catalyze two nonconsecutive
      transamidination reactions in the biosynthesis of the streptomycin family of
      antibiotics. L-Arginine:inosamine-phosphate amidinotransferase StrB1 from
      Streptomyces griseus (StrB1) was cloned as an N-terminal hexa-histidine fusion
      protein, purified by affinity chromatography, and crystallized, and its crystal
      structure was solved by Patterson search methods at 3.1 A resolution. The
      structure is composed of five betabeta alphabeta-modules which are arranged
      circularly into a pseudo-5-fold symmetric particle. The three-dimensional
      structure is closely related to the structure of human L-arginine:glycine
      amidinotransferase (AT), but five loops (the 40-, 170-, 220-, 250-, and 270-loop)
      are organized very differently. The major changes are found in loops around the
      active site which open the narrow active site channel of AT to form an open and
      solvent-exposed cavity. In particular, module II of StrB1 is AT-like but lacks a
      10-residue alpha-helix in the 170-loop. The concomitant reorganization of
      neighboring surface loops that surround the active site, i.e., the 40-loop and
      the 270-loop, results in an arrangement of loops which allows an unrestricted
      access of substrates to the cavity. However, the residues which are involved in
      substrate binding and catalysis are conserved in AT and StrB1 and are at
      equivalent topological positions, suggesting a similar reaction mechanism among
      amidinotransferases. The binding site for L-arginine had been deduced from its
      complex with AT. Molecular modeling revealed a possible binding mode for the
      second substrate scyllo-inosamine 4-phosphate.

PMID- 9922133
TI  - Dual function C-terminal domain of dynamin-1: modulation of self-assembly by
      interaction of the assembly site with SH3 domains.
AB  - Impairment of endocytosis by mutational targeting of dynamin-1 GTPases can result
      in paralysis and embryonic lethality. Dynamin-1 assembles at coated pits where it
      functions to cleave vesicles from donor membranes. Receptor endocytosis is
      modulated by SH3 (src homology 3) domain proteins, which directly bind to dynamin
      C-terminal proline motif sequences, affecting both the dynamin GTPase activity
      and its recruitment to coated pits. We have determined that dynamin-dynamin
      interactions, which are required for dynamin helix formation, involve these same
      SH3 domain-binding C-terminal proline motif sequences. Consequently, SH3 domain
      proteins induce the in vitro disassembly of dynamin helices. Our results
      therefore suggest the the dual function of the dynamin C-terminus (involving
      amino acids 800-840) permits direct regulation of dynamin assembly and function
      through interaction with SH3 domain proteins. Additionally, the N-terminal GTPase
      domain plays an important role in assembly. Finally, we show that the central PH
      (pleckstrin homology) domain exerts a strong inhibitory effect on the capacity
      for dynamin-1 self-assembly.

PMID- 9922134
TI  - Role of Arg100 and Arg264 from Anabaena PCC 7119 ferredoxin-NADP+ reductase for
      optimal NADP+ binding and electron transfer.
AB  - Previous studies and the crystal structure of Anabaena PCC 7119 FNR suggest that
      the side chains of Arg100 and Arg264 may be directly involved in the proper
      NADP+/NADPH orientation for an efficient electron-transfer reaction. Protein
      engineering on Arg100 and Arg264 from Anabaena PCC 7119 FNR has been carried out
      to investigate their roles in complex formation and electron transfer to NADP+
      and to ferredoxin/flavodoxin. Arg100 has been replaced with an alanine, which
      removes the positive charge, the long side chain, as well as the ability to form
      hydrogen bonds, while a charge reversal mutation has been made at Arg264 by
      replacing it with a glutamic acid. Results with various spectroscopic techniques
      indicate that the mutated proteins folded properly and that significant protein
      structural rearrangements did not occur. Both mutants have been kinetically
      characterized by steady-state as well as fast transient kinetic techniques, and
      the three-dimensional structure of Arg264Glu FNR has been solved. The results
      reported herein reveal important conceptual information about the interaction of
      FNR with its substrates. A critical role is confirmed for the long, positively
      charged side chain of Arg100. Studies on the Arg264Glu FNR mutant demonstrate
      that the Arg264 side chain is not critical for the nicotinamide orientation or
      for nicotinamide interaction with the isoalloxazine FAD moiety. However, this
      mutant showed altered behavior in its interaction and electron transfer with its
      protein partners, ferredoxin and flavodoxin.

PMID- 9922135
TI  - The microtubule-associated protein tau cross-links to two distinct sites on each
      alpha and beta tubulin monomer via separate domains.
AB  - The interaction between tubulin subunits and microtubule-associated proteins
      (MAPs) such as tau is fundamental for microtubule structure and function.
      Previous work has suggested that the "microtubule binding domain" of tau
      (composed of three or four imperfect 18-amino acid repeats, separated by 13- or
      14-amino acid inter-repeat regions) can bind to the C-terminal ends of both alpha
      and beta tubulin monomers. Here, using covalent cross-linking strategies, we
      demonstrate that there are two distinct tau cross-linking sites (designated as "C
      terminal" and "internal") on each alpha and beta tubulin monomer. The C-terminal
      tau cross-linking site is located within the 12 C-terminal amino acids of both
      alpha and beta tubulin, while the internal tau cross-linking site is located
      within the C-terminal one-third of alpha and beta tubulin but not within the last
      12 amino acids. In addition, we show that tau cross-links to the C-terminal site
      via its repeat 1 and/or the R1-R2 inter-repeat. The cross-linking of tau to the
      internal site is mediated by some subset of its other repeat units. Integrating
      these and earlier data with the 3.7 A resolution model of the alphabeta tubulin
      dimer recently presented by E. Nogales et al. [(1998), Nature 391, 199-203], we
      propose a new model for the tau-microtubule interaction.

PMID- 9922136
TI  - High-resolution solution NMR structure of the minimal active domain of the human
      immunodeficiency virus type-2 nucleocapsid protein.
AB  - The retroviral nucleocapsid (NC) protein is a multifunctional protein essential
      for RNA genome packaging and viral infectivity. The NC protein, NCp8, of the
      human immunodeficiency virus type-II (HIV-2) is a 49 amino acid peptide
      containing two zinc fingers, of the type C-X2-C-X4-H-X4-C, connected by seven
      amino acid residues, called the "basic amino acid cluster." It has been shown
      that the N-terminal zinc finger flanked by the basic amino acid cluster is the
      minimal active domain for the specific binding to viral RNA and other functions.
      However, the structure-activity relationships of NCp8 have not been investigated
      in detail. In the present study, the three-dimensional structure of a 29 amino
      acid peptide, including the minimal active domain (NCp8-fl), was determined by
      two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A
      total of 15 converged structures of NCp8-fl were obtained on the basis of 355
      experimental constraints, including 343 distance constraints obtained from
      nuclear Overhauser effect connectivities, 12 torsion angle (phi, chi1)
      constraints, and four constraints for zinc binding. The root-mean-square
      deviation of the 15 converged structures was 0.29 +/- 0.04 A for the backbone
      atoms (N, C(alpha), C) and 1.27 +/- 0.13 A for all heavy atoms. Interestingly,
      the basic amino acid cluster itself was defined well, with a loop-like
      conformation in which three arginine residues in the cluster and one arginine
      residue in the zinc finger are located approximately in the same plane of the
      molecule and are exposed to the solvent. The structure-activity relationships are
      discussed on the basis of the comparison of this well-defined structure with
      those of other NC proteins.

PMID- 9922137
TI  - Dual recognition of double-stranded DNA by 2'-aminoethoxy-modified
      oligonucleotides: the solution structure of an intramolecular triplex obtained by
      NMR spectroscopy.
AB  - The solution structure of an intramolecular triple helical oligonucleotide has
      been solved by NMR. The third strand of the pyrimidine x purine x pyrimidine
      triplex is composed of 2'-aminoethoxy-modified riboses, whereas the remaining
      part of the nucleic acid is DNA. The structure around the aminoethoxy
      modification was obtained with the help of selective isotope labeling in
      conjunction with isotope-editing experiments. Dinucleotide steps and interstrand
      connectivities, as well as the complete backbone conformation of the triplex,
      were derived from J-couplings, NOEs, and 31P chemical shifts. The structure of
      this triplex, solved by distance geometry, explains the extraordinary stability
      and increase in rate of triplex formation induced by 2'-aminoethoxy-modified
      oligonucleotides: apart from the formation of seven base triples, a well-defined
      hydrogen-bonding network is formed across the Crick-Hoogsteen groove involving
      the amino protons of the aminoethoxy moieties and the phosphates of the purine
      strand of the DNA. The modified strand adopts a conformation which is close to an
      A-type helix, whereas the DNA duplex conformation is best described as an unwound
      B-type helix. The groove dimensions and helical parameters of the 2'-aminoethoxy
      modified rY x dRdY triplex are surprisingly well conserved in comparison with DNA
      triplexes.

PMID- 9922138
TI  - Extended metal environments of cytochrome c oxidase structures.
AB  - The metals of the cytochrome c oxidase structures of the bovine heart
      mitochondrion (PDB code 1occ) and of the soil bacterium Paracoccus denitrificans
      (1arl) include a dicopper center (CuA), magnesium, two proximal hemes, a copper
      (CuB) atom, and a calcium. The mitochondrial structure also possesses a bound
      distant zinc ion. The extended environments of the metal sites are analyzed
      emphasizing residues of the second shell in terms of polarity, hydrophobicity,
      secondary structure, solvent accessibility, and H-bonding networks. A significant
      difference in the CuA metal environments concerns D-51 I in 1occ, absent from
      1arl. The D-51 I appears to play an important role in the proton pumping pathway.
      Our analysis uncovers several statistically significant residue clusters,
      including a cysteine-histidine-tyrosine cluster overlapping the CuA-Mg complex; a
      histidine-acidic cluster enveloping the environment of Mg, the two hemes, and
      CuB; and on the protein surface a mixed charge cluster, which may help stabilize
      the quaternary structure and/or mediate docking to cytochrome c. These clusters
      may constitute possible pathways for electron transfer, for O2 diffusion, and for
      H2O movement. Many hydrogen bonding relations along the interface of subunits I
      and II demarcate this surface as a potential participant in proton pumping.

PMID- 9922139
TI  - Structure-based design of potent inhibitors of scytalone dehydratase:
      displacement of a water molecule from the active site.
AB  - Scytalone dehydratase (SD) is a molecular target of inhibitor design efforts
      aimed at protecting rice plants from the fungal disease caused by Magnaporthe
      grisea. As determined from X-ray diffraction data of an SD-inhibitor complex
      [Lundqvist et al. (1994) Structure (London) 2, 937-944], there is an extended
      hydrogen-bonding network between protein side chains, the inhibitor, and two
      bound water molecules. From models of SD complexed to quinazoline and
      benztriazine inhibitors, a new class of potent SD inhibitors involving the
      displacement of an active-site water molecule were designed. We were able to
      increase inhibitory potency by synthesizing compounds with a nitrile
      functionality displayed into the space occupied by one of the crystallographic
      water molecules. Sixteen inhibitors are compared. The net conversion of potent
      quinazoline and benztriazine inhibitors to cyanoquinolines and cyanocinnolines
      increased binding potency 2-20-fold. Replacement of the nitrile with a hydrogen
      atom lowered binding affinity 100-30,000-fold. X-ray crystallographic data at
      1.65 A resolution on a SD-inhibitor complex confirmed that the nitrile
      functionality displaced the water molecule as intended and that a favorable
      orientation was created with tyrosines 30 and 50 which had been part of the
      hydrogen-bonding network with the water molecule. Additional data on inhibitors
      presented herein reveals the importance of two hydrogen-bonding networks toward
      inhibitory potency: one between Asn131 and an appropriately positioned inhibitor
      heteroatom and one between a bound water molecule and a second inhibitor
      heteroatom.

PMID- 9922140
TI  - The ice-binding site of sea raven antifreeze protein is distinct from the
      carbohydrate-binding site of the homologous C-type lectin.
AB  - Antifreeze proteins lower the freezing point of their solution by binding to ice
      and inhibiting its growth. One of several structurally different antifreeze
      proteins in fishes (type II) is homologous to the carbohydrate-recognition domain
      of Ca2+-dependent lectins and adopts the same three-dimensional fold. Type II
      antifreeze proteins from herring and smelt require Ca2+ for binding to ice,
      whereas this same antifreeze protein in sea raven binds to ice in the absence of
      Ca2+ and has only two of the five Ca2+-liganding amino acids that are present in
      the lectin. To locate the ice-binding site, site-directed mutants of the 15 kDa,
      globular, disulfide-bonded sea raven antifreeze protein were produced by
      secretion from Pichia pastoris. Pairs of amino acid replacements, insertions, and
      a peptide loop swap were made in the region equivalent to the sugar-binding site
      of the lectin that encompasses loops 3 and 4 and beta-sheets 7 and 8. Even the
      most extensive mutation caused only a 25% decrease in antifreeze activity and
      demonstrated that the residues corresponding to the Ca2+-binding site are only
      peripherally involved in ice binding. When adjacent surface residues were
      mutated, the replacement of one residue, Ser120 by His, caused a 35% decrease in
      activity by itself and an 80% loss in conjunction with the peptide loop swap
      mutation. This pivotal sea raven antifreeze protein amino acid does not coincide
      with the herring ice-binding epicenter, but is located within the region
      corresponding to the proposed CaCO3-binding surface of a third homologue, the
      pancreatic stone protein. Intron and exon structure of the sea raven AFP gene
      also suggests that it might be more closely related to the stone protein gene
      than to the lectin gene. These results support the notion that this family of
      proteins has evolved more than one binding surface from the same protein
      scaffold.

PMID- 9922141
TI  - Novel peptides selected to bind vascular endothelial growth factor target the
      receptor-binding site.
AB  - Peptides that inhibit binding of vascular endothelial growth factor (VEGF) to its
      receptors, KDR and Flt-1, have been produced using phage display. Libraries of
      short disulfide-constrained peptides yielded three distinct classes of peptides
      that bind to the receptor-binding domain of VEGF with micromolar affinities. The
      highest affinity peptide was also shown to antagonize VEGF-induced proliferation
      of primary human umbilical vascular endothelial cells. The peptides bind to a
      region of VEGF known to contain the contact surface for Flt-1 and the functional
      determinants for KDR binding. This suggests that the receptor-binding region of
      VEGF is a binding "hot spot" that is readily targeted by selected peptides and
      supports earlier assertions that phage-derived peptides frequently target protein
      protein interaction sites. Such peptides may lead to the development of
      pharmacologically useful VEGF antagonists.

PMID- 9922142
TI  - Crystal structure of the complex between VEGF and a receptor-blocking peptide.
AB  - Vascular endothelial growth factor (VEGF) is a specific and potent angiogenic
      factor and, therefore, a prime therapeutic target for the development of
      antagonists for the treatment of cancer. As a first step toward this goal, phage
      display was used to generate peptides that bind to the receptor-binding domain
      (residues 8-109) of VEGF and compete with receptor [Fairbrother, W. J.,
      Christinger, H. W., Cochran, A. G., Fuh, G., Keenan, C. J., Quan, C., Shriver, S.
      K., Tom, J. Y. K., Wells, J. A., and Cunningham, B. C. (1999) Biochemistry 38,
      17754-17764]. The crystal structure of VEGF in complex with one of these peptides
      was solved and refined to a resolution of 1.9 A. The 20-mer peptide is
      unstructured in solution and adopts a largely extended conformation when bound to
      VEGF. Residues 3-8 form a beta-strand which pairs with strand beta6 of VEGF via
      six hydrogen bonds. The C-terminal four residues of the peptide point away from
      the growth factor, consistent with NMR data indicating that these residues are
      flexible in the complex in solution. In contrast, shortening the N-terminus of
      the peptide leads to decreased binding affinities. Truncation studies show that
      the peptide can be reduced to 14 residues with only moderate effect on binding
      affinity. However, because of the extended conformation and the scarcity of
      specific side-chain interactions with VEGF, the peptide is not a promising lead
      for small-molecule development. The interface between the peptide and VEGF
      contains a subset of the residues recognized by a neutralizing Fab fragment and
      overlaps partially with the binding site for the Flt-1 receptor. The location of
      the peptide-binding site and the hydrophilic character of the interactions with
      VEGF resemble more the binding mode of the Fab fragment than that of the
      receptor.

PMID- 9922143
TI  - Structural basis for inhibition of the protein tyrosine phosphatase 1B by
      phosphotyrosine peptide mimetics.
AB  - Protein tyrosine phosphatases regulate diverse cellular processes and represent
      important targets for therapeutic intervention in a number of diseases. The
      crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with
      small molecule inhibitors based upon two classes of phosphotyrosine mimetics, the
      (difluoronaphthylmethyl)phosphonic acids and the fluoromalonyl tyrosines, have
      been determined to resolutions greater than 2.3 A. The fluoromalonyl tyrosine
      residue was incorporated within a cyclic hexapeptide modeled on an
      autophosphorylation site of the epidermal growth factor receptor. The structure
      of this inhibitor bound to PTP1B represents the first crystal structure of a non
      phosphonate-containing inhibitor and reveals the mechanism of phosphotyrosine
      mimicry by the fluoromalonyl tyrosine residue and the nature of its interactions
      within the catalytic site of PTP1B. In contrast to complexes of PTP1B with
      phosphotyrosine-containing peptides, binding of the fluoromalonyl tyrosine
      residue to the catalytic site of PTP1B is not accompanied by closure of the
      catalytic site WPD loop. Structures of PTP1B in complex with the
      (difluoronaphthylmethyl)phosphonic acid derivatives reveal that substitutions of
      the naphthalene ring modulate the mode of inhibitor binding to the catalytic site
      and provide the potential for enhanced inhibitor affinity and the generation of
      PTP-specific inhibitors. These results provide a framework for the rational
      design of higher affinity and more specific phosphotyrosine mimetic inhibitors of
      not only protein tyrosine phosphatases but also SH2 and PTB domains.

PMID- 9922145
TI  - Intrastrand cross-linked actin between Gln-41 and Cys-374. II. Properties of
      cross-linked oligomers.
AB  - Actin filaments partially cross-linked with ANP (N-(4-azido-2-nitrophenyl)
      putrescine between Gln-41 and Cys-374 on adjacent monomers in the long-pitch
      helix were depolymerized and fractionated into pools of longitudinal cross-linked
      dimers (s(o)20,w = 5.55 +/- 0.22 S), trimers (s(o)20,w = 6.93 +/- 0.12 S), and
      higher-order oligomers. Competition binding experiments of myosin subfragment
      (S1) to cross-linked dimers in the presence of pyrenyl G-actin revealed about 2
      orders of magnitude stronger binding of the first than that of the second S1
      molecule to actin dimer. Under similar conditions the unpolymerized cross-linked
      actin species activated the MgATPase of S1 only severalfold compared to 70-fold
      activation by F-actin. The cross-linked dimers, trimers, and oligomers were
      polymerized into filaments by MgCl2 faster than un-cross-linked actin. In
      electron micrographs these filaments appeared sometimes shorter and had greater
      tendency to bend than un-cross-linked actin filaments. Small amounts of cross
      linked actin dimers nucleated S1-induced polymerization of actin, but the
      polymerization by S1 was inhibited for pure populations of cross-linked dimers,
      trimers, and oligomers. The cross-linked dimers did not decrease the kinetic
      difference between the polymerization of actin by S1 isozymes S1(A1) and S1(A2).
      According to electron microscopy evidence, cross-linked actin oligomers
      polymerized by S1 yielded much shorter arrowhead structures than the un-cross
      linked actin. These results indicate the importance of lateral actin-actin
      interaction for the activation of myosin ATPase and the polymerization of actin
      by S1.

PMID- 9922144
TI  - Intrastrand cross-linked actin between Gln-41 and Cys-374. I. Mapping of sites
      cross-linked in F-actin by N-(4-azido-2-nitrophenyl) putrescine.
AB  - A new heterobifunctional photo-cross-linking reagent, N-(4-azido-2-nitrophenyl)
      putrescine (ANP), was synthesized and covalently bound to Gln-41 of rabbit
      skeletal muscle actin by a bacterial transglutaminase-mediated reaction. Up to
      1.0 mol of the reagent was incorporated per mole of G-actin; at least 90% of it
      was bound to Gln-41 while a minor fraction (about 8%) was attached to Gln-59. The
      labeled G-actin was polymerized, and the resulting F-actin was intermolecularly
      cross-linked by irradiation with UV light. The labeled and cross-linked peptides
      were isolated from either a complete or limited tryptic digest of cross-linked
      actin. In the limited digest the tryptic cleavage was restricted to arginine by
      succinylation of the lysyl residues. N-terminal sequencing and mass spectrometry
      indicated that the cross-linked peptides contained residues 40-50 (or 40-62 in
      the arginine limited digest) and residues 373-375, and that the actual cross
      linking took place between Gln-41 and Cys-374. This latter finding was also
      supported by the inhibition of Cys-374 labeling with a fluorescent probe in the
      cross-linked actin. The dynamic length of ANP, between 11.1 and 12.5 A,
      constrains to that range the distance between the gamma-carboxyl group of Gln-41
      in one monomer and the sulfur atom of Cys-374 in an adjacent monomer. This is
      consistent with the distances between these two residues on adjacent monomers of
      the same strand in the long-pitch helix in the structural models of F-actin
      [Holmes, K. C., Popp, D., Gebhard, W., and Kabsch, W. (1990) Nature 347, 44-49
      and Lorenz, M., Popp, D., and Holmes, K. C. (1993) J. Mol. Biol. 234, 826-836].
      The effect of cross-linking on the function of actin is described in the
      companion papers.

PMID- 9922146
TI  - Intrastrand cross-linked actin between Gln-41 and Cys-374. III. Inhibition of
      motion and force generation with myosin.
AB  - Structural and functional properties of intrastrand, ANP (N-(4-azido-2
      nitrophenyl)-putrescine) cross-linked actin filaments, between Gln-41 and Cys-374
      on adjacent monomers, were examined for several preparations of such actin.
      Extensively cross-linked F-actin (with 12% un-cross-linked monomers) lost at 60
      degrees C the ability to activate myosin ATPase at a 100-fold slower rate and
      unfolded in CD melting experiments at a temperature higher by 11 degrees C than
      the un-cross-linked actin. Electron microscopy and image reconstruction of these
      filaments did not reveal any gross changes in F-actin structure but showed a
      change in the orientation of subdomain 2 and a decrease in interstrand
      connectivity. Rigor and weak (in the presence of ATP) myosin subfragment (S1)
      binding and acto-S1 ATPase did not show major changes upon 50% and 90% ANP cross
      linking of F-actin; the Kd and Km values were little affected by the cross
      linking, and the Vmax decreased by 50% for the extensively cross-linked actin.
      The cross-linking of actin (50%) decreased the mean speed and the number of
      sliding filaments in the in vitro motility assays by approximately 35% while the
      relative force, as measured by using external load in these assays, was inhibited
      by approximately 25%. The mean speed of actin filaments decreased with the
      increase in their cross-linking and approached 0 for the 90% cross-linked actin.
      Also examined were actin filaments reassembled from cross-linked and purified ANP
      cross-linked dimers, trimers, and oligomers. All of these filaments had the same
      acto-S1 ATPase and rigor S1 binding properties but different behavior in the in
      vitro motility assays. Filaments made of cross-linked dimers moved at
      approximately 50% of the speed of the un-cross-linked actin. The movement of
      filaments made of cross-linked trimers was inhibited more severely, and the
      oligomer-made filaments did not move at all. These results show the uncoupling
      between force generation and other events in actomyosin interactions and
      emphasize the role of actin filament structure and dynamics in the contractile
      process.

PMID- 9922147
TI  - Calmodulin binding to myosin light chain kinase begins at substoichiometric Ca2+
      concentrations: a small-angle scattering study of binding and conformational
      transitions.
AB  - We have used small-angle scattering to study the calcium dependence of the
      interactions between calmodulin (CaM) and skeletal muscle myosin light chain
      kinase (MLCK), as well as the conformations of the complexes that form.
      Scattering data were measured from equimolar mixtures of a functional MLCK and
      CaM or a mutated CaM (B12QCaM) incompetent to bind Ca2+ in its N-terminal domain,
      with increasing Ca2+ concentrations. To evaluate differences between CaM-enzyme
      versus CaM-peptide interactions, similar Ca2+ titration experiments were
      performed using synthetic peptides based on the CaM-binding sequence from MLCK
      (MLCK-I). Our data show there are different determinants for CaM binding the
      isolated peptide sequence compared to CaM binding to the same sequences within
      the enzyme. For example, binding of either CaM or B12QCaM to the MLCK-I peptide
      is observed even in the presence of EGTA, whereas binding of CaM to the enzyme
      requires Ca2+. The peptide studies also show that the conformational collapse of
      CaM requires both the N and C domains of CaM to be competent for Ca2+ binding as
      well as interactions with each end of MLCK-I, and it occurs at approximately 2
      mol of Ca2+/mol of CaM. We show that CaM binding to the MLCK enzyme begins at
      substoichiometric concentrations of Ca2+ (< or = 2 mol of Ca2+/mol of CaM), but
      that the final compact structure of CaM with the enzyme requires saturating Ca2+.
      In addition, MLCK enzyme does bind to 2Ca2+ x B12QCaM, although this complex is
      more extended than the complex with native CaM. Our results support the
      hypothesis that CaM regulation of MLCK involves an initial binding step at less
      than saturating Ca2+ concentrations and a subsequent activation step at higher
      Ca2+ concentrations.

PMID- 9922148
TI  - Contribution to Tl+, K+, and Na+ binding of Asn776, Ser775, Thr774, Thr772, and
      Tyr771 in cytoplasmic part of fifth transmembrane segment in alpha-subunit of
      renal Na,K-ATPase.
AB  - The sequence Y771TLTSNIPEIT781P in the fifth transmembrane segment of the alpha
      subunit of Na,K-ATPase is unique among cation pump proteins. Here, in search of
      the molecular basis for Na,K specificity, alanine and conservative substitutions
      were directed to six oxygen-carrying residues in this segment. The contribution
      of the residues to cation binding was estimated from direct binding of Tl+
      [Nielsen, et al. (1998) Biochemistry 37, 1961-1968], K+ displacement of ATP
      binding at equilibrium, and Na+-dependent phosphorylation from ATP in the
      presence of oligomycin. As an intrinsic control, substitution of Thr781 had no
      effect on Tl+(K+) or Na+ binding. There are several novel observations from this
      work. First, the carboxamide group of Asn776 is equally important for binding
      Tl+(K+) or Na+, whereas a shift of the position of the carboxamide of Asn776
      (Asn776Gln) causes a large depression of Na+ binding without affecting the
      binding of Tl+(K+). Second, Thr774 is important for Na+ selectivity because
      removal of the hydroxyl group reduces the binding of Na+ with no effect on
      binding of Tl+(K+). Removal of the methyl groups of Thr774 or Thr772 reduces
      binding of both Tl+(K+) and Na+, whereas the hydroxyl group of Thr772 does not
      contribute to cation binding. Furthermore, the hydroxyl groups of Ser775 and
      Tyr771 are important for binding both Tl+(K+) and Na+. The data suggest that
      rotating or tilting of the cytoplasmic part of the fifth transmembrane segment
      may adapt distances between coordinating groups and contribute to the distinctive
      Na+/K+ selectivity of the pump.

PMID- 9922149
TI  - Regulation of band 3 rotational mobility by ankyrin in intact human red cells.
AB  - Ankyrin mutations and combined spectrin and ankyrin deficiency are prominent
      features of red blood cells (RBCs) in patients with hereditary spherocytosis
      (HS). Band 3 is the most abundant integral protein in the human RBC membrane.
      Previous studies have shown that the lateral mobility, but not the rotational
      mobility, of band 3 is increased in RBCs from patients with severe autosomal
      recessive HS and selective spectrin deficiency. These observations are consistent
      with the steric hindrance model of lateral mobility restriction. Here we use the
      fluorescence photobleaching recovery and polarized fluorescence depletion
      techniques to measure the lateral and rotational mobility of band 3 in intact
      RBCs from six patients with HS, ankyrin mutations, and combined spectrin and
      ankyrin deficiency. As predicted by the steric hindrance model, the lateral
      diffusion rate of band 3 is greater in spectrin- and ankyrin-deficient RBCs than
      in control cells, and the magnitude of the increase correlates with the degree of
      spectrin deficiency. Unlike RBCs from patients with HS and selective spectrin
      deficiency, however, HS RBCs with ankyrin mutations exhibit a marked increase in
      band 3 rotational diffusion. The magnitude of the increase correlates inversely
      with the ankyrin/band 3 ratio and with the fraction of band 3 retained in the
      membrane skeleton following detergent extraction. These data suggest that ankyrin
      deficiency relaxes rotational constraints on the major (slowly rotating)
      population of band 3 molecules. Increases in band 3 rotation could be due to
      release of band 3 from low-affinity binding sites on ankyrin.

PMID- 9922150
TI  - Effect of ADP on binding of skeletal S1 to F-actin.
AB  - The proximity of skeletal myosin subfragment-1 (S1) to actin, and its orientation
      with respect to thin filaments of single muscle fibers, were compared in the
      presence and in the absence of ADP. The proximity was assessed by the efficiency
      of carbodiimide-induced cross-linking and the orientation by polarization of
      fluorescence of probes attached to the essential light chains. ADP made no
      difference in proximity or orientation when the molar ratio of S1 to actin was
      low or high. However, at the intermediate ratios, ADP made a significant
      difference. Strong dissociating agents, AMP-PNP and PPi, made significant
      differences at all ratios. To explain this behavior, it is unnecessary to invoke
      the ADP-induced "swinging" of the tail of S1. Rather, it is simply explained by
      the "two-state" model which we proposed earlier, in which S1 binds to one or to
      two actin protomers, depending on the saturation of the filaments with S1s. The
      dissociation induced by the ADP shifts the equilibrium between the two bound
      states. At high and low degrees of saturation, ADP is unable to significantly
      decrease the amount of S1 bound to F-actin. However, at intermediate saturation
      levels, ADP causes significantly more S1s to bind to two actins. These results
      suggest that the ADP-induced changes seen at the intermediate molar ratios are
      due to the dissociation-induced reorientation of S1.

PMID- 9922152
TI  - Characterization of the transthyretin acid denaturation pathways by analytical
      ultracentrifugation: implications for wild-type, V30M, and L55P amyloid fibril
      formation.
AB  - Analytical ultracentrifugation methods were utilized to further characterize the
      acid denaturation pathways of wild-type, V30M, and L55P transthyretin (TTR) that
      generate intermediates leading to amyloid fibril formation and possibly the
      diseases senile systemic amyloidosis and familial amyloid polyneuropathy.
      Equilibrium and velocity methods were employed herein to characterize the TTR
      quaternary structural requirements for amyloid fibril formation. From neutral to
      slightly acidic conditions (pH 7.5-5.1), wild-type transthyretin (0.2-0.3 mg/mL,
      100 mM KCl, 37 degrees C) exists as a tetramer and is incapable of fibril
      formation. Under more acidic conditions (pH 5 to 3.9), tetrameric wild-type TTR
      slowly dissociates to a monomer having an alternatively folded tertiary
      structure(s) that self-assembles at physiological concentration (0.2 mg/mL) into
      a ladder of quaternary structural intermediates of increasing molecular weight.
      These intermediates appear to be on the pathway of amyloid fibril formation,
      since they ultimately disappear when amyloid fibrils are observed. The V30M and
      L55P TTR variants exhibit similar acid denaturation pathways, with the exception
      that dissociation of the tetramer to the monomeric amyloidogenic intermediate
      occurs at a higher pH and to a much greater extent, allowing the quaternary
      structural intermediates to be readily observed by velocity methods. Partial
      denaturation and assembly of the monomeric amyloidogenic intermediate(s) occur at
      pH 5.4 for V30M and L55P TTR over a 72 h period, during which wild-type TTR
      maintains its normal tetrameric three-dimensional structure. Interestingly, the
      L55P and V30M familial amyloid polyneuropathy (FAP) associated variants form
      amyloid protofilaments at pH 7.5 (37 degrees C) after several weeks of
      incubation, suggesting that the activation barriers for TTR tetramer dissociation
      to the monomeric amyloidogenic intermediate are much lower for the FAP variants
      relative to wild-type TTR, which does not form amyloid or amyloid protofilaments
      under these conditions. This study establishes the key role of the monomeric
      amyloidogenic intermediate and its self-assembly into a ladder of quaternary
      structural intermediates for the formation of wild-type, V30M, and L55P
      transthyretin amyloid fibrils.

PMID- 9922151
TI  - Identification of a receptor mediating absorption of dietary cholesterol in the
      intestine.
AB  - Here we show that scavenger receptor class B type I is present in the small
      intestine brush border membrane where it facilitates the uptake of dietary
      cholesterol from either bile salt micelles or phospholipid vesicles. This
      receptor can also function as a port for several additional classes of lipids,
      including cholesteryl esters, triacylglycerols, and phospholipids. It is the
      first receptor demonstrated to be involved in the absorption of dietary lipids in
      the intestine. In liver and steroidogenic tissues, the physiological ligand of
      this receptor is high-density lipoprotein. We show that binding of high-density
      lipoprotein and apolipoprotein A-I to the brush border membrane-resident receptor
      inhibits uptake of cholesterol (sterol) into the brush border membrane from lipid
      donor particles. This finding lends further support to the conclusion that
      scavenger receptor BI catalyzes intestinal cholesterol uptake. Our findings
      suggest new therapeutic approaches for limiting the absorption of dietary
      cholesterol and reducing hypercholesterolemia and the risk of atherosclerosis.

PMID- 9922154
TI  - Mutations in the activation loop tyrosine of the oncoprotein v-Fps.
AB  - Mutations were made in the activation loop tyrosine of the kinase domain of the
      oncoprotein v-Fps to assess the role of autophosphorylation in catalysis. Three
      mutant proteins, Y1073E, Y1073Q, and Y1073F, were expressed and purified as
      fusion proteins of glutathione-S-transferase from Escherichia coli and their
      catalytic properties were evaluated. Y1073E, Y1073Q, and Y1073F have k(cat)
      values that are reduced by 5-, 35-, and 40-fold relative to the wild-type enzyme,
      respectively. For all mutant enzymes, the Km values for ATP and a peptide
      substrate, EAEIYEAIE, are changed by 0.4-2-fold compared to the wild-type enzyme.
      The slopes for the plots of relative turnover versus solvent viscosity
      [(k(cat))eta] are 0.71 +/- 0.08, 0.10 +/- 0.06, and approximately 0 for wild
      type, Y1073Q, and Y1073E, respectively. These results imply that the phosphoryl
      transfer rate constant is reduced by 19- and 130-fold for Y1073E and Y1073Q
      compared to the wild-type enzyme. The dissociation constant of the substrate
      peptide is 1.5-2.5-fold lower for the mutants compared to wild type. The
      inhibition constant for EAEIFEAIE, a competitive inhibitor, is unaffected for
      Y1073E and raised 3-fold for Y1073Q compared to wild type. Y1073E and Y1073Q are
      strongly activated by free magnesium to the same extent and the apparent affinity
      constant for the metal is similar to that for the wild-type enzyme. The data
      indicate that the major role of autophosphorylation in the tyrosine kinase domain
      of v-Fps is to increase the rate of phosphoryl transfer without greatly affecting
      active-site accessibility or the local environment of the activating metal.
      Finally, the similar rate enhancements for phosphoryl transfer in v-Fps compared
      to protein kinase A [Adams et al. (1995) Biochemistry 34, 2447-2454] upon
      autophosphorylation suggest a conserved mechanism for communication between the
      activation loop and the catalytic residues of these two enzymes.

PMID- 9922153
TI  - Evidence that C1q binds specifically to CH2-like immunoglobulin gamma motifs
      present in the autoantigen calreticulin and interferes with complement
      activation.
AB  - Calreticulin (CRT) is located predominantly in the endoplasmic reticulum (ER) of
      cells, where it functions as a quality control controller of protein folding.
      However, CRT is also a prevalent autoantigen in patients with systemic lupus
      erythematosus (SLE), where its release from the cell may arise as a results of
      dysfunctional apoptosis and inefficient removal of ER vesicles, which are an
      abundant source of CRT and other autoantigens. Indicative of this is the presence
      of autoantibodies against CRT in the sera of 40-60% of all SLE patients. Once
      released into the circulation, CRT might bind directly to C1q and we have
      suggested that this association may result in a defect in C1q-mediated clearance
      of antigen-antibody complexes. It has been previously shown that CRT under
      physiological salt conditions binds to the globular head of C1q. It is known that
      the globular head region of C1q binds to the CH2 domain in the Fc portion of
      immunoglobulin gamma (IgG). The N-terminal half of CRT contains a number of short
      regions of 7-10 amino acids that show sequence similarity to the putative C1q
      binding region in the CH2 domain of IgG. By use of a series of 92 overlapping CRT
      synthetic peptides, a number of C1q binding sites on the CRT molecule have been
      identified, including several containing a CH2-like motif similar to the ExKxKx
      C1q binding motif found in the CH2 domain of IgG. A number of these peptides were
      shown to inhibit binding of C1q to IgG and reduce binding of native CRT to C1q.
      Moreover, several of the peptides were capable of inhibiting the classical
      pathway of complement activation. These studies have identified specific binding
      sites on the CRT molecule for C1q and lend support to the hypothesis that
      interaction of CRT with C1q may interfere with the ability of C1q to associate
      with immune complexes in autoimmune-related disorders.

PMID- 9922155
TI  - Apolipoprotein E and antioxidants have different mechanisms of inhibiting
      Alzheimer's beta-amyloid fibril formation in vitro.
AB  - We compared the mechanisms of apolipoprotein E- (apoE-) and antioxidant- (AO-)
      mediated inhibition of beta-amyloid fibril (fA beta) formation in vitro, based on
      a nucleation-dependent polymerization model using fluorescence spectroscopy with
      thioflavin T. We first applied a kinetic plot to transform a sigmoidal time
      course curve of fA beta formation from freshly prepared amyloid beta-peptides (A
      beta) into a straight line. Mathematical treatment of this plot demonstrated that
      the above-described sigmoidal curve is a logistic curve and provided us with a
      kinetic parameter t(1/2), the time when the rate of fA beta formation is maximum.
      t(1/2) of beta-amyloids (A beta) (1-42) and (1-40) were 18.7 +/- 1.7 min and 6.3
      +/- 0.2 h, respectively (mean +/- SD, n = 3) and were independent of the initial
      A beta concentration examined. Although apoE extended t(1/2) of both A betas in a
      dose-dependent manner, AO did not. On the other hand, the final amount of fA beta
      formed was decreased by both apoE and AO dose-dependently. We then analyzed the
      effect of apoE and AO on the extension reaction of fA beta, based on a first
      order kinetic model. Although apoE extended the time to proceed to equilibrium in
      a dose-dependent manner, AO did not. On the other hand, both apoE and AO dose
      dependently decreased the final amount of fA beta formed. These results indicate
      that apoE and AO inhibit fA beta formation in vitro by different mechanisms and
      suggest the existence of multiple pharmacological targets for the prevention of
      fA beta formation.

PMID- 9922156
TI  - Probing the topography of HIV-1 nucleocapsid protein with the alkylating agent N
      ethylmaleimide.
AB  - Retroviral nucleocapsid (NC) proteins contain one or two zinc fingers (ZFs)
      consisting of a CCHC peptide motif that coordinates Zn(II). Mutational and
      biochemical analyses have shown that NC ZFs are directly involved in multiple
      stages of viral replication, including genomic RNA encapsidation, virus
      maturation, and the early infection process. The multiple roles of the conserved
      retroviral ZFs make them attractive targets for antiviral agents. We have
      previously shown that a variety of chemical compounds can inactivate the whole
      virus by attacking NC ZFs. For the enhancement of the specificity of antiviral
      reagents, it is desirable to have a detailed knowledge of the spatial
      organization of reactive sites on the NC protein in its free and oligonucleotide
      bound states. A method has been developed using chemical probes to assess the
      reactivity of specific Cys residues in the NC protein, and is being used to
      investigate the topography of ZFs in different contexts. In this study we focus
      on the reaction mechanism of N-ethylmaleimide (NEM) with free HIV-1 NCp7 protein.
      Our results show that the conformation of free NCp7 restricts the initial site of
      attack to Cys-49 (the most distal Cys residue in the second ZF) and that the
      reactivity of thiols in full-length protein differs from that of the isolated ZF
      peptides. A moderate to near complete reduction in reaction rate was observed
      when NCp7 was complexed with different oligonucleotides. These findings provide a
      set of experimentally determined parameters that can serve to guide computational
      modeling of the NC protein and will be useful for the rational design of drugs
      directed against retroviral ZFs.

PMID- 9922157
TI  - Multiple factors determine the selection of the ectodomain cleavage site of human
      cell surface macrophage colony-stimulating factor.
AB  - Human cell surface macrophage colony-stimulating factor (CSF-1256, M-CSF alpha)
      is converted to a soluble growth factor by a regulated proteolytic cleavage
      process at amino acid residues 157-159. We have previously shown that multiple
      factors specified by the juxtamembrane region determine the cleavage efficiency
      [Deng, P., Rettenmier, C. W., and Pattengale, P. K. (1996) J. Biol. Chem. 271,
      16338-16343]. In the present paper, we studied the effect of various deletion,
      insertion, and substitution mutations at or near the cleavage site on both the
      number and size of cleaved CSF-1(256) products to identify the mechanisms by
      which the cleavage sites are selected. Deletion of regions 161-162 or 163-165, C
      terminal to the cleavage site, as well as deletion of region 150-156, N-terminal
      to the cleavage site, each yielded a single cleavage product that was smaller
      than that derived from the wild type (WT). In these experiments cleavage
      apparently occurred at a specific distance from the transmembrane domain.
      Insertion of three additional residues between the normal cleavage site and the
      transmembrane domain yielded one major product that was the same size as the
      processed form of WT CSF-1(256). In this case the selection of the cleavage site
      was apparently determined by the amino acid sequence of the juxtamembrane region
      rather than by the distance from the transmembrane domain. Other amino acid
      substitutions at the cleavage site caused changes in cleavage site selection,
      providing additional evidence for the role of amino acid sequence in cleavage
      site selection. Finally, a comparison of cleavage site selection in the presence
      and absence of tunicamycin treatment showed that N-glycosylation of certain
      mutant forms of CSF-1(256) sterically interfered with protease accessibility,
      which in turn had an effect on the selection of the site used for cleavage. Taken
      together, these results indicate that cleavage site selection is determined by
      the amino acid sequence of the juxtamembrane region, the distance of the site
      from the transmembrane domain, and steric accessibility of the protease.

PMID- 9922158
TI  - Intermediates in the reaction of fully reduced cytochrome c oxidase with
      dioxygen.
AB  - The reduction of dioxygen to water by cytochrome c oxidase was monitored in the
      Soret region following photolysis of the fully reduced CO complex. Time-resolved
      optical absorption difference spectra collected between 373 and 521 nm were
      measured at delay times from 50 ns to 50 ms and analyzed using singular value
      decomposition and multiexponential fitting. Five processes were resolved with
      apparent lifetimes of 0.9 micros, 8 micros, 36 micros, 103 micros, and 1.2 ms. A
      mechanism is proposed and spectra of intermediates are extracted and compared to
      model spectra of the postulated intermediates. The model builds on an earlier
      mechanism that used data only from the visible region (Sucheta et al. (1997)
      Biochemistry 36, 554-565) and provides a more complete mechanism that fits
      results from both spectral regions. Intermediate 3, the ferrous-oxy complex
      (compound A) decays into a 607 nm species, generally referred to as P, which is
      converted to a 580 nm ferryl form (Fo) on a significantly faster time scale. The
      equilibrium constant between P and Fo is 1. We propose that the structure of P is
      a3(4+)=O CuB2+-OH- with an oxidizing equivalent residing on tyrosine 244, located
      close to the binuclear center. Upon conversion of P to Fo, cytochrome a donates
      an electron to the tyrosine radical, forming tyrosinate. Subsequently a proton is
      taken up by tyrosinate, forming F(I) [a3(4+)=O CuB2+-OH- a3+ CuA+]. This is
      followed by rapid electron transfer from CuA to cytochrome a to produce F(II)
      [a3(4+)=O CuB2+-OH- a2+ CuA2+].

PMID- 9922159
TI  - Membrane topography of the T domain of diphtheria toxin probed with single
      tryptophan mutants.
AB  - The membrane insertion and translocation of diphtheria toxin, which is induced in
      vivo by low pH, is thought to be directed by the hydrophobic alpha-helices of its
      transmembrane (T) domain. In this study the structure of membrane-associated T
      domain was examined. Site-directed mutants of the T domain with single Trp
      residues were prepared at the two naturally occurring positions, 206 (near the N
      terminal end of helix TH1) and 281 (within helix TH5), as well as at three
      residues in helix TH9, in which the substitutions F355W (near the N-terminal end
      of TH9), I364W (close to the center of TH9), and Y375W (near the C-terminal end
      of TH9) were made. All these mutants were found to undergo the low-pH-induced
      conformational change observed with wild-type T domain and insert into model
      membranes at low pH. The location of Trp residues relative to the lipid bilayer
      was characterized in model membrane vesicles by fluorescence emission and by
      quenching with nitroxide-labeled phospholipids. In TH9, residue 375 was shallowly
      inserted, residue 364 deeply inserted, and residue 355 located at an intermediate
      depth. Residues 206 and 281 exhibited moderately deep insertion. It was also
      found, in agreement with our previous study using bimane-labeled protein (Wang et
      al. (1997) J. Biol. Chem. 272, 25091-25098), that TH9 switches from a relatively
      shallowly inserted state to a more deeply inserted state when the concentration
      of the T domain in the membrane is increased or the thickness of the membrane
      bilayer is decreased. In particular, the depth of residue 355 was found to
      increase under the conditions giving deeper insertion. In contrast, residue 375
      remained shallowly located in both states, as predicted from its location on the
      polar C-terminus of TH9. It is concluded that TH1 and TH5 insert into the lipid
      bilayer in both T domain conformations. In addition, Trp depths suggest that even
      in the shallowly inserted state there is a significant degree of insertion of
      TH9. These results suggest regions of the T domain in addition to the hydrophobic
      TH8/TH9 hairpin insert into membranes. Models for the structure of the membrane
      inserted T domain are discussed.

PMID- 9922160
TI  - Reaction of myeloperoxidase compound I with chloride, bromide, iodide, and
      thiocyanate.
AB  - Myeloperoxidase plays a fundamental role in oxidant production by neutrophils.
      The enzyme uses hydrogen peroxide to oxidize chloride (Cl-), bromide (Br-),
      iodide (I-), and the pseudohalide thiocyanate (SCN-) to their respective
      hypohalous acids. This study for the first time presents transient kinetic
      measurements of the oxidation of these halides and thiocyanate by the
      myeloperoxidase intermediate compound I, using the sequential mixing stopped-flow
      technique. At pH 7 and 15 degrees C, the two-electron reduction of compound I to
      the native enzyme by Cl- has a second-order rate constant of (2.5 +/- 0.3) x
      10(4) M(-1) s(-1), whereas reduction of compound I by SCN- has a second-order
      rate constant of (9.6 +/- 0.5) x 10(6) M(-1) s(-1). Iodide [(7.2 +/- 0.7) x 10(6)
      M(-1) s(-1)] is shown to be a better electron donor for compound I than Br- [(1.1
      +/- 0.1) x 10(6) M(-1) s(-1)]. The pH dependence studies suggest that compound I
      reduction by (pseudo-)halides is controlled by a residue with a pKa of about 4.6.
      The protonation of this group is necessary for optimum (pseudo-)halide anion
      oxidation. These transient kinetic results are underlined by steady-state
      spectral and kinetic investigations. SCN- is shown to be most effective in
      shifting the system myeloperoxidase/hydrogen peroxide from the peroxidatic cycle
      to the halogenation cycle, whereas iodide is shown to be more effective than
      bromide which in turn is much more effective than chloride. Decreasing pH
      increases the rate of this transition. Our results show that thiocyanate is an
      important substrate of myeloperoxidase in most environments and that
      hypothiocyanate is likely to contribute to leukocyte antimicrobial activity.

PMID- 9922161
TI  - Hydrogen bonding, solvent exchange, and coupled proton and electron transfer in
      the oxidation and reduction of redox-active tyrosine Y(Z) in Mn-depleted core
      complexes of photosystem II.
AB  - The redox-active tyrosines, Y(Z) and Y(D), of Photosystem II are oxidized by
      P680+ to the neutral tyrosyl radical. This oxidation thus involves the transfer
      of the phenolic proton as well as an electron. It has recently been proposed that
      tyrosine Y(Z) might replace the lost proton by abstraction of a hydrogen atom or
      a proton from a water molecule bound to the manganese cluster, thereby increasing
      the driving force for water oxidation. To compare and contrast with the intact
      system, we examine here, in a simplified Mn-depleted PSII core complex, isolated
      from a site-directed mutant of Synechocystis PCC 6803 lacking Y(D), the role of
      proton transfer in the oxidation and reduction of Y(Z). We show how the oxidation
      and reduction rates for Y(Z), the deuterium isotope effect on these rates, and
      the Y(Z)* - Y(Z) difference spectra all depend on pH (from 5.5 to 9.5). This
      simplified system allows examination of electron-transfer processes over a
      broader range of pH than is possible with the intact system and with more
      tractable rates. The kinetic isotope effect for the oxidation of P680+ by Y(Z) is
      maximal at pH 7.0 (3.64). It decreases to lower pH as charge recombination, which
      shows no deuterium isotope, starts to become competitive with Y(Z) oxidation. To
      higher pH, Y(Z) becomes increasingly deprotonated to form the tyrosinate, the
      oxidation of which at pH 9.5 becomes extremely rapid (1260 ms(-1)) and no longer
      limited by proton transfer. These observations point to a mechanism for the
      oxidation of Y(Z) in which the tyrosinate is the species from which the electron
      occurs even at lower pH. The kinetics of oxidation of Y(Z) show elements of rate
      limitation by both proton and electron transfer, with the former dominating at
      low pH and the latter at high pH. The proton-transfer limitation of Y(Z)
      oxidation at low pH is best explained by a gated mechanism in which Y(Z) and the
      acceptor of the phenolic proton need to form an electron/proton-transfer
      competent complex in competition with other hydrogen-bonding interactions that
      each have with neighboring residues. In contrast, the reduction of Y(Z)* appears
      not to be limited by proton transfer between pH 5.5 and 9.5. We also compare, in
      Mn-depleted Synechocystis PSII core complexes, Y(Z) and Y(D) with respect to
      solvent accessibility by detection of the deuterium isotope effect for Y(Z)
      oxidation and by 2H ESEEM measurement of hydrogen-bond exchange. Upon incubation
      of H2O-prepared PSII core complexes in D2O, the phenolic proton of Y(Z) is
      exchanged for a deuterium in less than 2 min as opposed to a t(1/2) of about 9 h
      for Y(D). In addition, we show that Y(D)* is coordinated by two hydrogen bonds.
      Y(Z)* shows more disordered hydrogen bonding, reflecting inhomogeneity at the
      site. With 2H ESEEM modulation comparable to that of Y(D)*, Y(Z)* would appear to
      be coordinated by two hydrogen bonds in a significant fraction of the centers.

PMID- 9922162
TI  - Quinol and cytochrome oxidases in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The genome of Synechocystis sp. PCC 6803 contains three sets of genes for
      terminal respiratory oxidases: the previously identified cytochrome aa3-type
      cytochrome c oxidase (CtaI), a second putative oxidase (CtaII) that we interpret
      to be a cytochrome bo-type quinol oxidase, and a putative cytochrome bd quinol
      oxidase (Cyd). Genes for the two putative oxidases were cloned, and deletion
      constructs were made. Strains that lack one, two, or all three of the oxidases
      were generated. Deletion of the respiratory oxidases had no effect on
      photoautotrophic or photomixotrophic growth. Strains that lack one oxidase
      respire at near-wild-type rates, whereas those that lack both CtaI and Cyd do not
      respire. Thus, CtaII does not play a significant role in cellular metabolism
      under the conditions tested. An expression construct containing cydAB from
      Synechocystis sp. PCC 6803 was able to restore aerobic growth in a strain of
      Escherichia coli that lacks the cytochrome bo oxidase and the cytochrome bd
      oxidase encoded by cydAB. These results show that the cydAB operon from
      Synechocystis sp. PCC 6803 encodes a functional quinol oxidase. Deletion of Cyd
      and/or CtaII in strains lacking photosystem I did not change the fluorescence
      decay kinetics after illumination, and therefore, these oxidases do not
      significantly utilize reducing equivalents in the thylakoid membrane. This,
      combined with our inability to delete CtaI from strains lacking photosystem I,
      suggests that CtaI is the major oxidase on the thylakoid membrane and that Cyd is
      localized mostly on the cytoplasmic membrane. Transcripts for ctaDI were detected
      under all growth conditions tested, while transcripts for cydA and ctaEII could
      only be detected in cells grown at low light intensity (5 microE m(-2) s(-1)).

PMID- 9922164
TI  - His...Asp catalytic dyad of ribonuclease A: conformational stability of the wild
      type, D121N, D121A, and H119A enzymes.
AB  - Residue His119 acts as an acid/base during the cleavage/hydrolysis reactions
      catalyzed by bovine pancreatic ribonuclease A (RNase A). In the native enzyme,
      His119 forms a hydrogen bond with Asp121. This His...Asp dyad is conserved in all
      homologous pancreatic ribonucleases of known sequence. Yet, replacing Asp121 with
      an asparagine or alanine residue does not have a substantial effect on either
      structure or function [Schultz, L. W., Quirk, D. J., and Raines, R. T. (1998)
      Biochemistry 37, 8886-8898]. Here, the pH dependencies of the conformational
      stabilities of wild-type RNase A and the D121N, D121A, and H119A variants were
      determined by monitoring thermal stability over the pH range 1.2-6.0. Replacing
      Asp121 with an asparagine or alanine residue results in a loss of conformational
      stability at pH 6.0 of deltadeltaG(o) = 2.0 kcal/mol, from a total of 9.0
      kcal/mol. The magnitude of this loss is similar to that to transition-state
      binding during catalysis. As the pH decreases, the aspartate residue becomes
      protonated and deltadeltaG(o) decreases. D121N RNase A and D121A RNase A are
      approximately equivalent in conformational stability. This equivalence arises
      from compensating changes to enthalpy and entropy. A general analytical method
      was developed to determine the value of the pKa of a residue in the native and
      denatured states of a protein by comparing the pH-stability profile of the wild
      type protein with that of a variant in which the ionizable residue is replaced
      with a nonionizable one. Accordingly, Asp121 was found to have pKa values of
      approximately 2.4 and 3.4 in the native and denatured states, respectively, of
      wild-type RNase A. This change in pKa can account fully for the differential
      effects of pH on the conformational stabilities of the wild-type and variant
      proteins. We conclude that the His...Asp catalytic dyad in pancreatic
      ribonucleases has two significant roles: (1) to position the proper tautomer of
      His119 for catalysis and (2) to enhance the conformational stability of the
      native enzyme. Most enzymic residues contribute to catalysis or stability (or
      neither). Asp121 of RNase A is a rare example of a residue that contributes
      equally to both.

PMID- 9922163
TI  - Structural and thermochemical characterization of lipoxygenase-catechol
      complexes.
AB  - A complex between native, iron(II) soybean lipoxygenase 3 and 4-nitrocatechol, a
      known inhibitor of the enzyme, has been detected by isothermal titration
      calorimetry and characterized by X-ray crystallography. The compound moors in the
      central cavity of the protein close to the essential iron atom, but not in a
      bonding arrangement with it. The iron ligands experience a significant
      rearrangement upon formation of the complex relative to their positions in the
      native enzyme; a water molecule becomes bound to iron in the complex, and one
      histidine ligand moves away from the iron to become involved in a hydrogen
      bonding interaction with the catechol. These changes in position result in a
      trigonal pyramid coordination geometry for iron in the complex. Molecular
      modeling and force field calculations predict more than one stable complex
      between 4-nitrocatechol and the central cavity of lipoxygenase 3, but the
      interaction having the small molecule in the same orientation as the one found in
      the crystal structure was the most favorable. These observations reveal specific
      details of the interaction between lipoxygenase and a small molecule and raise
      the possibility that changes in the ligand environment of the iron atom could be
      a feature of the product activation reaction or the catalytic mechanism.

PMID- 9922165
TI  - Ca2+-dependent structural changes in C-type mannose-binding proteins.
AB  - C-type animal lectins are a diverse family of proteins which mediate cell-surface
      carbohydrate-recognition events through a conserved carbohydrate-recognition
      domain (CRD). Most members of this family possess a carbohydrate-binding activity
      that depends strictly on the binding of Ca2+ at two sites, designated 1 and 2, in
      the CRD. The structural transitions associated with Ca2+ binding in C-type
      lectins have been investigated by determining high-resolution crystal structures
      of rat serum mannose-binding protein (MBP) bound to one Ho3+ in place of Ca2+,
      and the apo form of rat liver MBP. The removal of Ca2+ does not affect the core
      structure of the CRD, but dramatic conformational changes occur in the loops. The
      most significant structural change in the absence of Ca2+ is the isomerization of
      a cis-peptide bond preceding a conserved proline residue in Ca2+ site 2. This
      bond adopts the cis conformation in all Ca2+-bound structures, whereas both cis
      and trans conformations are observed in the absence of Ca2+. The pattern of
      structural changes in the three loops that interact with Ca2+ is dictated in
      large part by the conformation of the prolyl peptide bond. The highly conserved
      nature of Ca2+ site 2 suggests that the transitions observed in MBPs are general
      features of Ca2+ binding in C-type lectins.

PMID- 9922166
TI  - Coupling of prolyl peptide bond isomerization and Ca2+ binding in a C-type
      mannose-binding protein.
AB  - A proline residue flanked by two polar residues is a highly conserved sequence
      motif in the Ca2+- and carbohydrate-binding site of C-type animal lectins.
      Crystal structures of several C-type lectins have shown that the two flanking
      residues are only observed to act as Ca2+ ligands when the peptide bond preceding
      the proline residue is in the cis conformation. In contrast, structures of the
      apo- and one-ion forms of mannose-binding proteins (MBPs) reveal that, when the
      Ca2+-binding site is empty, the peptide bond preceding the proline can adopt
      either the cis or trans conformation, and distinct structures in adjacent regions
      are associated with the two proline isomers. In this work, measurements of Ca2+
      induced changes in intrinsic tryptophan fluorescence, and fluorescence energy
      transfer from tryptophan to Tb3+, reveal a slow conformational change in rat
      liver MBP (MBP-C) accompanying the binding of either Ca2+ or Tb3+. The Ca2+
      induced increase in intrinsic tryptophan fluorescence shows biphasic kinetics: a
      burst phase with a rate constant greater than 1 s(-1) is followed by a slow phase
      with a single-exponential rate constant ranging from 0.01 to 0.05 s(-1) (36
      degrees C) that depends on the concentration of Ca2+. Likewise, addition of EGTA
      to Ca2+-bound or Tb3+-bound MBP-C causes a decrease in intrinsic tryptophan
      fluorescence with biphasic kinetics consisting of a burst phase with a rate
      constant greater than 1 s(-1), followed by a slow phase with a single-exponential
      rate constant of 0.065 s(-1). In contrast, Tb3+ fluorescence produced by resonant
      energy transfer from MBP-C decreases in a single kinetic phase with a rate
      constant greater than 1 s(-1), implying that the slow change in tryptophan
      fluorescence monitors a conformational change that is not limited in rate by ion
      dissociation. The rate constants of the slow phases accompanying Ca2+ binding and
      release are strongly affected by temperature and are weakly accelerated by the
      prolyl isomerase cyclophilin. These data strongly suggest that the binding of
      either Ca2+ or Tb3+ to MBP-C is coupled to a conformational change that involves
      the cis-trans isomerization of a peptide bond. Fitting of the data to kinetic
      models indicates that, in the absence of Ca2+, the proline in approximately 80%
      of the molecules is in the trans conformation. The slow kinetics associated with
      cis-trans proline isomerization may be exploited by endocytic receptors to
      facilitate sorting of carbohydrate-bearing ligands from the receptor in the
      endosome.

PMID- 9922168
TI  - Pressure-denatured state of Escherichia coli ribonuclease HI as monitored by
      Fourier transform infrared and NMR spectroscopy.
AB  - Pressure denaturation of Escherichia coli ribonuclease HI (RNase HI) was studied
      by Fourier transform infrared (FTIR) and two-dimensional NMR spectroscopy at pD*
      3.0 and 25 degrees C. A reversible transition in the pressure range of 0.1-1090
      MPa was observed with second-derivative FTIR experiments. A cooperative and
      gradual denaturation, involving both the secondary and tertiary structures, was
      observed between 240 and 450 MPa. The two peaks at 1629 and 1652 cm(-1), due to
      beta-strands and alpha-helices, respectively, did not fully disappear after the
      denaturation, and are different from the spectra of the random coil peptides. The
      hydrogen-deuterium exchange rates of the individual backbone amide protons were
      determined by heteronuclear NMR combined with the pressure-jump technique at 500,
      650, and 850 MPa. Although most of the amides protected in the native structure
      are also highly protected in the pressure-denatured state, the rate constants
      (0.048 +/- 0.007 min(-1)) for the amide protons at 500 MPa are similar regardless
      of their locations, which is an indication of the EX1 mechanism of hydrogen
      deuterium exchange. The pressure-denatured state of RNase HI at 500 MPa
      represents a novel denatured state, which is different from a typical molten
      globule state at atmospheric pressure (0.1 MPa), from the viewpoint of the
      homogeneous rate constants. The observations at 650 MPa are essentially the same
      as those at 500 MPa. However, at 850 MPa, the amide exchange rates for the highly
      hydrophobic C-terminal half of alpha-helix I are significantly slower than those
      for the other part of the protein, which can be interpreted as a hydrophobic
      collapse centered at the C-terminal half of alpha-helix I.

PMID- 9922167
TI  - Evaluation of the role of His447 in the reaction catalyzed by cholesterol
      oxidase.
AB  - Cholesterol oxidase catalyzes the oxidation and isomerization of cholesterol to
      cholest-4-en-3-one via cholest-5-en-3-one. It has been proposed that His447 acts
      as the general base catalyst for oxidation, and that the resulting imidazolium
      ion formed acts as an electrophile for isomerization. In this work, we undertook
      an assessment of the proposed dual roles of His447 in the oxidation and
      isomerization reactions. To test its role, we constructed five mutants, H447Q,
      H447N, H447E, H447D, and H447K, that introduce hydrogen bond donors and acceptors
      and carboxylate bases at this position, and a sixth mutant, E361Q, to test the
      interplay between His447 and Glu361. These mutants were characterized using
      steady-state kinetics and deuterium substrate and solvent isotope effects. For
      those mutants that catalyze either oxidation of cholesterol or isomerization of
      cholest-5-en-3-one, the Km's vary no more than 3-fold relative to wild type.
      H447K is inactive in both oxidation (> 100,000-fold reduced) and isomerization
      assays (> 10,000-fold reduced). H447E and H447D do not catalyze oxidation (>
      100,000-fold reduced), but do catalyze isomerization, 10(4) times slower than
      wild type. The k(cat) for H447Q is 120-fold lower than wild type for oxidation,
      and the same as wild type for isomerization. The k(cat) for H447N is 4400-fold
      lower than wild type for oxidation, and is 30-fold lower than wild type for
      isomerization. E361Q does not catalyze isomerization (> 10,000-fold reduced), and
      the k(cat) for oxidation is 30-fold lower than wild type. The substrate deuterium
      kinetic isotope effects for the wild-type and mutant-catalyzed oxidation
      reactions suggest that mutation of His447 to an amide results in a change of the
      rate-determining step from hydride transfer to hydroxyl deprotonation. The
      deuterium solvent and substrate kinetic isotope effects for isomerization
      indicate that an amide at position 447 is an effective electrophile to catalyze
      formation of a dienolic intermediate. Moreover, consideration of kinetic and
      structural results together suggests that a hydrogen bonding network involving
      His447, Glu361 and Asn485, Wat541, and substrate serves to position the substrate
      and coordinate general base and electrophilic catalysis. That is, in addition to
      its previously demonstrated role as base for deprotonation of carbon-4 during
      isomerization, Glu361 has a structural role and may act as a general base during
      oxidation. The His447, Asn485, Glu361, and Wat541 residues are conserved in other
      GMC oxidoreductases. Observation of this catalytic tetrad in flavoproteins of
      unknown function may be diagnostic for an ability to oxidize unactivated
      alcohols.

PMID- 9922169
TI  - Monitoring the sizes of denatured ensembles of staphylococcal nuclease proteins:
      implications regarding m values, intermediates, and thermodynamics.
AB  - Fluorescence and size-exclusion chromatography (SEC) are used to monitor urea
      denaturation of wild-type staphylococcal nuclease (SN) as well as the m+ and m-
      mutants A69T and V66W, respectively. It is found that the SEC partition
      coefficient, 1/Kd, is directly proportional to the Stokes radii of proteins. From
      the Stokes radii, the denatured ensembles of the three proteins are found to be
      highly compact in the limit of low urea concentration and expand significantly
      with increasing urea concentration. The m values from fluorescence-detected
      denaturation of the SN proteins are generally considered to reflect the relative
      sizes of denatured ensembles. However, the rank order of m values of the SN
      proteins studied do not correspond to the rank order of denatured ensemble sizes
      detected by 1/Kd, suggesting that m values reflect more than just surface area
      increases on denaturation. SEC provides two complementary ways to demonstrate the
      existence of intermediates in urea denaturation and illustrates that V66W
      undergoes a three-state transition. Fluorescence-detected urea denaturations of
      A69T and wt SN do not correspond with 1/Kd-detected denaturation profiles, a
      result that would ordinarily mean that the transitions are non-two-state.
      However, this interpretation fails to recognize the rapidly changing size and
      thermodynamic character of the denatured ensembles of these proteins both within
      and outside of the transition zone. The implications of the changing sizes and
      thermodynamic character of the denatured ensembles for SN proteins are manifold,
      requiring a reconsideration of the thermodynamics of proteins whose denatured
      ensembles behave as those of SN proteins.

PMID- 9922170
TI  - Synthesis of (2R,3R)-erythro- and (2R,3S)-threo-fluoromalate using malic
      dehydrogenase; stereoselectivity of malic dehydrogenase.
AB  - 3-Fluorooxalacetate is a substrate for malic dehydrogenase. When enzymatic
      reduction is slower than the rate of epimerization of the two enantiomers, only
      (2R,3R)-erythro-fluoromalate is formed. Conversely, when a high enzyme level and
      excess of NADH lead to reduction that is fast relative to the epimerization rate,
      equal amounts of (2R,3R)-erythro- and (2R,3S)-threo-fluoromalate are formed.
      These data suggest that the V/K value for reduction of the R enantiomer to give
      the erythro isomer is approximately 100 times greater than for reduction of the S
      enantiomer to give the threo isomer. The equilibrium constant for the oxidation
      of fluoromalate is an order of magnitude less favorable than for oxidation of
      malate, while the equilibrium deuterium isotope effect from deuteration at C-2 of
      the substrate is 1.09 for fluoromalate versus 1.18 for malate. These effects
      reflect the inductive effect of fluorine at the 3-position.

PMID- 9922171
TI  - Determination of the kinetic and chemical mechanism of malic enzyme using (2R,3R)
      erythro-fluoromalate as a slow alternate substrate.
AB  - (2R,3R)-erythro-Fluoromalate, but not the threo isomer, is a slow substrate for
      chicken liver malic enzyme with either NADP or 3-acetylpyridine-NADP (APADP) as
      the other substrate. The Km for erythro-fluoromalate is similar to that of
      malate, but the turnover number with NADP is 3300-fold slower, although 5.5-fold
      faster with APADP than with NADP. Deuteration of fluoromalate at C-2 gave an
      isotope effect on V/K of 1.39 with NADP and 3.32 with APADP. With NADP, the 13C
      isotope effects at C-4 were 1.0490 with unlabeled and 1.0364 with deuterated
      fluoromalate. With APADP, the corresponding values were 1.0138 and 1.0087. These
      data show that the mechanism is stepwise with both nucleotide substrates, in
      contrast to the reaction of malate and APADP, which was postulated to be
      concerted by Karsten et al. [Karsten, W. E., and Cook, P. F. (1994) Biochemistry
      33, 2096-2103], a conclusion recently shown to be correct by Edens et al. [Edens,
      W. A., Urbauer, J. L., and Cleland, W. W. (1997) Biochemistry 36, 1141-1147]. To
      explain the effect of deuteration on the 13C isotope effect with APADP, it is
      necessary to assume a secondary 13C isotope effect at C-4 on the hydride transfer
      step of approximately 1.0064 (assuming 5.7 as the intrinsic primary deuterium
      isotope effect and 1.054 as the product of the 13C equilibrium isotope effect on
      hydride transfer and the intrinsic 13C isotope effect on decarboxylation). The
      secondary 13C isotope effect on hydride transfer is thought to result from
      hyperconjugation between the carbonyl group and C-4 of the enzyme-bound
      fluorooxaloacetate intermediate.

PMID- 9922172
TI  - Dynamics and thermodynamics of the regulatory domain of human cardiac troponin C
      in the apo- and calcium-saturated states.
AB  - The contraction of cardiac and skeletal muscles is triggered by the binding of
      Ca2+ to their respective troponin C (TnC) proteins. Recent structural data of
      both cardiac and skeletal TnC in both the apo and Ca2+ states have revealed that
      the response to Ca2+ is fundamentally different for these two proteins. For
      skeletal TnC, binding of two Ca2+ to sites 1 and 2 leads to large changes in the
      structure, resulting in the exposure of a hydrophobic surface. For cardiac TnC,
      Ca2+ binds site 2 only, as site 1 is inactive, and the structures show that the
      Ca2+-induced changes are much smaller and do not result in the exposure of a
      large hydrophobic surface. To understand the differences between regulation of
      skeletal and cardiac muscle, we have investigated the effect of Ca2+ binding on
      the dynamics and thermodynamics of the regulatory N-domain of cardiac TnC (cNTnC)
      using backbone 15N nuclear magnetic resonance relaxation measurements for
      comparison to the skeletal system. Analysis of the relaxation data allows for the
      estimation of the contribution of changes in picosecond to nanosecond time scale
      motions to the conformational entropy of the Ca2+-binding sites on a per residue
      basis, which can be related to the structural features of the sites. The results
      indicate that binding of Ca2+ to the functional site in cNTnC makes the site more
      rigid with respect to high-frequency motions; this corresponds to a decrease in
      the conformational entropy (TdeltaS) of the site by 2.2 kcal mol(-1). Although
      site 1 is defunct, binding to site 2 also decreases the conformational entropy in
      the nonfunctional site by 0.5 kcal mol(-1). The results indicate that the Ca2+
      binding sites in the regulatory domain are structurally and energetically coupled
      despite the inability of site 1 to bind Ca2+. Comparison between the cardiac and
      skeletal isoforms in the apo state shows that there is a decrease in
      conformational entropy of 0.9 kcal mol(-1) for site 1 of cNTnC and little
      difference for site 2.

PMID- 9922174
TI  - Probing the interplay between the two steps of group I intron splicing:
      competition of exogenous guanosine with omega G.
AB  - One largely unexplored question about group I intron splicing is how the cleavage
      and ligation steps of the reaction are coordinated. We describe a simple in vitro
      trans-splicing model system in which both steps take place, including the
      exchange of ligands in the guanosine-binding site that must occur between the two
      steps. Using this model system, we show that the switch is accomplished by
      modulating the relative affinity of the binding site for the two ligands. While
      the terminal guanosine of the intron (omegaG) and exogenous guanosine compete for
      binding during the first step of splicing, no competition is apparent during the
      second step, when omegaG is bound tightly. These results help explain how the
      ribozyme orchestrates progression through the splicing reaction. In addition to
      providing a new tool to ask basic questions about RNA catalysis, the trans
      splicing model system will also facilitate the development of therapeutically
      useful group I ribozymes that can repair mutant mRNAs.

PMID- 9922173
TI  - Mutations in the cytosolic DnaJ homologue, YDJ1, delay and compromise the
      efficient translation of heterologous proteins in yeast.
AB  - The Saccharomyces cerevisiae YDJ1 gene encodes a yeast homologue of DnaJ, an
      Escherichia coli molecular chaperone and regulator of Hsp70 function. We examined
      the function of Ydj1p in vivo by analyzing the activity and production of firefly
      luciferase (FFLux) and green fluorescent protein (GFP) after inducible expression
      in yeast strains containing a wild type or a mutant YDJ1 gene. Although FFLux and
      GFP mRNA levels were similar in the wild type and mutant strains, the FFLux
      protein was translated about half as efficiently in the ydj1-151 mutant compared
      to the wild type strain; the lower FFLux level was not the result of increased
      FFLux turnover in the mutant. In contrast, GFP translation was significantly
      delayed in the ydj1-151 mutant compared to the wild type strain. Surprisingly, we
      observed that FFLux and GFP mRNA bound efficiently to polysomes in the ydj1-151
      mutant. Analysis of polysome profiles also revealed a modest increase in the
      amount of 60S ribosomal subunits in the ydj1-151 strain, consistent with a
      translation defect in the mutant, although the Ydj1 protein was not found to be
      associated with polysomes. To determine whether the inducible expression of an
      endogenous yeast protein was also less efficient in the ydj1-151 strain, we
      examined the inducible synthesis of the yeast TATA-binding protein (TBP) but
      observed no translation defect. Statistical analysis of the FFLux, GFP, and TBP
      encoding genes suggests that Ydj1p facilitates the expression of proteins that
      are poorly translated because both FFLux and GFP contain an abundance of codons
      that are rarely used in yeast.

PMID- 9922175
TI  - Enhanced rotational dynamics of the phosphorylation domain of the Ca-ATPase upon
      calcium activation.
AB  - We have used labeling conditions that permit the specific and covalent attachment
      of erythrosin isothiocyanate (Er-ITC) to Lys464 within the phosphorylation domain
      of the Ca-ATPase in skeletal sarcoplasmic reticulum membranes. These labeling
      conditions do not interfere with high-affinity ATP binding, phosphoenzyme
      formation, or phosphoenzyme hydrolysis [Huang, S., Negash, S., and Squier, T. C.
      (1998) Biochemistry 37, 6949-6957]. Thus, we can use frequency-domain
      phosphorescence spectroscopy to measure the rotational dynamics of the Ca-ATPase
      stabilized in different enzymatic states corresponding to the absence of bound
      ligands (E), calcium activation (E x Ca2), the presence of bound nucleotide (E x
      ATP), and formation of phosphoenzyme (E-P). We resolve three rotational
      correlation times corresponding to (i) a large-amplitude domain motion of the
      phosphorylation domain (phi1 approximately 5 +/- 1 micros), (ii) overall protein
      rotational motion with respect to the membrane normal (phi2 approximately 50 +/-
      10 micros), and (iii) the rotational motion of the SR vesicles (phi3
      approximately 1.1 +/- 0.4 ms). No differences are observed in the rotational
      dynamics of E, E x ATP, or E-P, indicating that phosphoenzyme formation or
      nucleotide binding result in no global structural changes involving the
      phosphorylation domain. In contrast, calcium activation enhances the amplitude of
      motion of the phosphorylation domain. These observed calcium-dependent changes in
      rotational dynamics result from structural changes within a single Ca-ATPase
      polypeptide chain, since protein-protein interactions do not change upon calcium
      binding. Thus, calcium binding induces concerted domain motions within a single
      Ca-ATPase polypeptide chain that may play a critical role in facilitating
      substrate binding and utilization.

PMID- 9922176
TI  - Promoter recognition by Escherichia coli RNA polymerase: effects of the UP
      element on open complex formation and promoter clearance.
AB  - Escherichia coli promoters for transcription of ribosomal and tRNAs are greatly
      activated by an A+T-rich "UP" element upstream of the -35 region. These same
      promoters have also been found to otherwise deviate in several respects from the
      consensus promoter sequence. Here we present the results of a kinetic
      characterization of the interaction of Escherichia coli RNA polymerase with UP
      element-containing promoters which by virtue of consensus or near-consensus
      sequence features should be among the most optimal that can be encountered by
      Escherichia coli RNA polymerase. We show that for such promoters, (1) the second
      order rate constant describing formation of the initial (closed) complex is close
      to that expected for a diffusion-limited process, (2) the extent of activation by
      the UP element is temperature-sensitive, (3) the UP element accelerates a process
      after DNA binding by RNA polymerase, and (4) the presence of the UP element
      delays promoter clearance upon addition of nucleoside triphosphates to preformed
      RNA polymerase-promoter complexes. Finally, we provide evidence in support of
      models which describe the DNA melting process accompanying open complex formation
      as initiating in the -10 promoter region and progressing in the downstream
      direction.

PMID- 9922177
TI  - Targeting of human retrotransposon integration is directed by the specificity of
      the L1 endonuclease for regions of unusual DNA structure.
AB  - L1 elements are polyA retrotransposons which inhabit the human genome. Recent
      work has defined an endonuclease (L1 EN) encoded by the L1 element required for
      retrotransposition. We report the sequence specificity of this nicking
      endonuclease and the physical basis of its DNA recognition. L1 endonuclease is
      specific for the unusual DNA structural features found at the TpA junction of
      5'(dTn-dAn) x 5'(dTn-dAn) tracts. Within the context of this sequence,
      substitutions which generate a pyrimidine-purine junction are tolerated, whereas
      purine-pyrimidine junctions greatly reduce or eliminate nicking activity. The A
      tract conformation of the DNA substrate 5' of the nicked site is required for L1
      EN nicking. Chemical or physical unwinding of the DNA helix enhances L1
      endonuclease activity, while disruption of the adenine mobility associated with
      TpA junctions reduces it. Akin to the protein-DNA interactions of DNase I, L1
      endonuclease DNA recognition is likely mediated by minor groove interactions.
      Unlike several of its homologues, however, L1 EN exhibits no AP endonuclease
      activity. Finally, we speculate on the implications of the specificity of the L1
      endonuclease for the parasitic relationship between retroelements and the human
      genome.

PMID- 9922178
TI  - Electron paramagnetic resonance spectroscopic measurement of Mn2+ binding
      affinities to the hammerhead ribozyme and correlation with cleavage activity.
AB  - Efficient phosphodiester bond cleavage activity by the hammerhead ribozyme
      requires divalent cations. Toward understanding this metal ion requirement, the
      Mn2+-binding properties of hammerhead model ribozymes have been investigated
      under dilute solution conditions, using electron paramagnetic resonance
      spectroscopy (EPR) to detect free Mn2+ in the presence of added ribozyme. Numbers
      and affinities of bound Mn2+ were obtained at pH 7.8 (5 mM triethanolamine) in
      the presence of 0, 0.1, and 1.0 M NaCl for an RNA-DNA model consisting of a 13
      nucleotide DNA "substrate" hybridized to a 34-nucleotide RNA "enzyme" [Pley, H.
      W., Flaherty, K. M., and McKay, D. B. (1994) Nature 372, 68-74]. In 0.1 M NaCl,
      two classes of Mn2+ sites are found with n1 = 3.7 +/- 0.4, Kd(1) = 4 +/- 1 microM
      (type 1) and n2 = 5.2 +/- 0.4, Kd(2) = 460 +/- 130 microM (type 2). The high
      affinity type 1 sites are confirmed for an active RNA-RNA hybrid (34-nucleotide
      RNA enzyme:13-nucleotide RNA substrate) by EPR measurements at low Mn2+
      concentrations. Decreasing NaCl concentration results in an increased number of
      bound Mn2+ per hammerhead. By contrast, a binding titration in 1 M NaCl indicates
      that a single Mn2+ site with apparent Kd approximately 10 microM is populated in
      low concentrations of Mn2+, and apparent cooperative effects at higher Mn2+
      concentrations result in population of a similar total number of Mn2+ sites (n1 =
      8-10) as found in 0.1 M NaCl. Mn2+-dependent activity profiles are similar for
      the active RNA-RNA hybrid in 0.1 and 1 M NaCl. Correlation with binding
      affinities determined by EPR indicates that hammerhead activity in 0.1 M NaCl is
      only observed after all four of the high-affinity Mn2+ sites are occupied, rises
      with population of the type 2 sites, and is independent of Mn2+ concentrations
      corresponding to > 8-9 Mn2+ bound per hammerhead. Equivalent measurements in 1 M
      NaCl demonstrate a rise in activity with the cooperative transition observed in
      the Mn2+ binding curve. These measurements indicate that, over this NaCl
      concentration range, hammerhead ribozyme activity is influenced by population of
      a specific set of divalent cation sites.

PMID- 9922179
TI  - Binding of the catalytic subunit of protein phosphatase-1 to the ryanodine
      sensitive calcium release channel protein.
AB  - A number of studies have reported that the activity of the ryanodine-sensitive
      calcium release channel (ryanodine receptor) in the junctional sarcoplasmic
      reticulum of skeletal and cardiac muscle can be modulated by protein
      phosphorylation-dephosphorylation through activation of endogenous protein
      kinases and/or by addition of exogenous protein kinases and protein phosphatases.
      In this study, we have investigated the possibility that protein phosphatase-1
      (PP1) is targeted to the junctional sarcoplasmic reticulum by the direct
      isolation of PP1-binding proteins on PP1-Sepharose affinity columns. The results
      show that the ryanodine receptor of both skeletal and cardiac muscle bind to this
      affinity support, and are released at supraphysiological salt concentrations in a
      relatively pure state. Reciprocal experiments demonstrated that PP1 binds to the
      immobilized muscle ryanodine receptor. The direct binding of PP1 to the ryanodine
      receptor was supported by the finding that tryptic fragments of the receptor were
      retained on PP1-Sepharose. The ability of PP1 to dephosphorylate the ryanodine
      receptor that was phosphorylated by protein kinase A was also demonstrated. These
      studies show that PP1 is targeted to the junctional sarcoplasmic reticulum by
      binding to the ryanodine receptor, and provide a biochemical basis for the
      possibility that PP1 may play a role in the regulation of calcium flux via
      protein phosphorylation-dephosphorylation mechanisms.

PMID- 9922180
TI  - Identification of the cyclosporin-binding site in P-glycoprotein.
AB  - The binding site of cyclosporin A to P-glycoprotein was characterized by using a
      multidrug-resistant Chinese hamster ovary cell line. P-glycoprotein photolabeled
      with diazirine-cyclosporin A analogue was purified by a two-step process
      involving continuous elution electrophoresis followed by wheat germ agglutinin
      agarose precipitation. The cyclosporin A covalently bound to P-glycoprotein and
      to subsequent proteolytic fragments was detected by Western blot analysis using a
      monoclonal antibody against cyclosporin A. Proteolytic digestion of purified P
      glycoprotein by V8 generated a major fragment of 15 kDa photolabeled by
      cyclosporin A, while proteolysis of P-glycoprotein photolabeled by [125I]
      iodoaryl azidoprazosin generated a major fragment of 7 kDa. Limited proteolysis
      of cyclosporin A-photolabeled P-glycoprotein with trypsin indicated that the
      major binding site for cyclosporin A was in the C-terminal half of the protein.
      This cyclosporin A binding site was further characterized with chemical agents (N
      chlorosuccinimide, cyanogen bromide, and 2-nitro-5-thiocyanobenzoate). These
      three chemical agents established a proteolytic profile of P-glycoprotein for
      fragments photolabeled with cyclosporin A and for fragments that contained the
      C494 and C219 epitopes. The smallest fragments generated by these chemical agents
      include the transmembrane domains (TMs) 10, 11, and 12 of P-glycoprotein. When
      the fragments generated by these chemical agents are aligned, the region that
      binds cyclosporin A is reduced to the 953-1007 residues. These combined results
      suggest that the major binding site of cyclosporin A occurs between the end of TM
      11 and the end of TM 12.

PMID- 9922181
TI  - Kinetic mechanism of the enantioselective conversion of styrene oxide by epoxide
      hydrolase from Agrobacterium radiobacter AD1.
AB  - Epoxide hydrolase from Agrobacterium radiobacter AD1 catalyzes the
      enantioselective hydrolysis of styrene oxide with an E value of 16. The (R)
      enantiomer of styrene oxide is first converted with a k(cat) of 3.8 s(-1), and
      the conversion of the (S)-enantiomer is inhibited. The latter is subsequently
      hydrolyzed with a k(cat) of 10.5 s(-1). The pre-steady-state kinetic parameters
      were determined for both enantiomers with stopped-flow fluorescence and rapid
      quench techniques. For (R)-styrene oxide a four-step mechanism was needed to
      describe the data. It involved the formation of a Michaelis complex that is in
      rapid equilibrium with free enzyme and substrate, followed by rapid and
      reversible alkylation of the enzyme. A unimolecular isomerization of the
      alkylated enzyme precedes the hydrolysis of the covalent intermediate, which
      could be observed due to an enhancement of the intrinsic protein fluorescence
      during this step. The conversion of (S)-styrene oxide could be described by a
      three-step mechanism, which also involved reversible and rapid formation of an
      ester intermediate from a Michaelis complex and its subsequent slow hydrolysis as
      the rate-limiting step. The unimolecular isomerization step has not been observed
      for rat microsomal epoxide hydrolase, for which a kinetic mechanism was recently
      established [Tzeng, H.-F., Laughlin, L. T., Lin, S., and Armstrong, R. N. (1996)
      J. Am. Chem. Soc. 118, 9436-9437]. For both enantiomers of styrene oxide, the Km
      value was much lower than the substrate binding constant K(S) due to extensive
      accumulation of the covalent intermediate. The enantioselectivity was more
      pronounced in the alkylation rates than in the rate-limiting hydrolysis steps.
      The combined reaction schemes for (R)- and (S)-styrene oxide gave an accurate
      description of the epoxide hydrolase catalyzed kinetic resolution of racemic
      styrene oxide.

PMID- 9922182
TI  - Lymphomas in solid organ transplantation.
AB  - BACKGROUND: The purpose of this investigation was to identify and characterize
      abdominal lymphomas as they occur in a large solid-organ-transplant population.
      METHODS: A large transplant population was isolated, and all patients developing
      an abdominal lymphoma were identified. These patients were further characterized
      after review of their medical records and radiologic examinations. RESULTS:
      Twenty-eight (1%) of 2925 patients developed lymphoma following transplantation.
      Of these 28 patients, 14 developed abdominal manifestations of disease. Examples
      of the wide variety of abdominal manifestations of posttransplant lymphoma are
      presented. Most of these patients had positive titers for Epstein-Barr virus and
      were treated with cyclosporin as a part of their immunotherapy. The majority of
      patients died secondary to this aggressive disease process. CONCLUSION: The
      development of lymphoma following solid organ transplantation is more common than
      in the general population. One-half of the patients in our study population
      developed abdominal manifestations of this disease.

PMID- 9922183
TI  - Jejunogastric intussusception: a rare complication of gastric surgery.
AB  - Jejunogastric intussusception is a rare complication of gastric surgery. We
      report a case in a 41-year-old woman subjected to gastrojejunostomy with truncal
      vagotomy 3 years before for pyloric stenosis. The jejunogastric intussusception
      was diagnosed by upper gastrointestinal series, ultrasonography, and computed
      tomography. Surgical management consisted of reduction and fixation. Treatment
      should be as early as possible to prevent gangrene of the invaginated segment.

PMID- 9922184
TI  - Percutaneous transhepatic obliteration for esophagojejunal varices after total
      gastrectomy.
AB  - A 59-year-old man experienced hematemesis 5 years after a total gastrectomy and
      Roux-en-Y esophagojejunostomy for carcinoma of the cardia. Endoscopic examination
      revealed the esophagojejunal blue small varices with cherry-red spots.
      Percutaneous transhepatic portography showed that the varices were supplied by
      the vein of the ascending jejunal limb. The 3-French microcatheter was inserted
      into this vein through the 5-French catheter, and 0.5 mL of absolute ethanol and
      2 mL of ethanolamine oleate with iopamidol were injected, which visualized the
      esophagojejunal varices and obliterated varices at the same time. There were no
      complications during the operation, and the subsequent clinical course showed no
      further bleeding. We conclude that percutaneous transhepatic obliteration with a
      3-French microcatheter is one of the most effective means of treating
      esophagojejunal small varices arising after a total gastrectomy.

PMID- 9922185
TI  - Computed tomography of superior mesenteric vein thrombosis following
      appendectomy.
AB  - During a 5-year period, superior mesenteric vein (SMV) thrombosis was detected
      with computed tomography (CT) in six patients shortly after an appendectomy. No
      sign of SMV was present at appendectomy, and a period of more than 2 weeks free
      of clinical symptoms had elapsed between the appendectomy and the onset of the
      SMV thrombosis. In four cases, the appendicitis was complicated. These patients
      had nonspecific signs and symptoms, although two of them had elevation of blood
      hepatic enzyme levels. In all cases, postcontrast CT demonstrated enlargement of
      the SMV, with well-defined enhancement of the vascular wall and an intraluminal
      clot. In one case, CT showed extension of the thrombus to the portal vein with
      the presence of low-attenuation areas in the liver, consistent with hepatic
      infarcts. Two patients had predisposing diseases: idiopathic hypersplenism in one
      case and chronic hepatic disease in the other. SMV thrombosis is a possible
      complication of appendicitis, and early appendectomy in appendicitis can prevent
      this complication. Moreover, as in any abdominal surgery, early appendectomy may
      be complicated by thrombosis of the SMV, thus creating problems of postoperative
      diagnosis. The complication is more frequent when the initial operation is
      performed under difficult conditions (peritonitis), or when the patient presents
      with a coagulopathy. CT is useful in the diagnosis of SMV thrombosis, thus
      leading to early management with anticoagulant therapy, with a view to avoiding
      complications such as intestinal ischemia, portal vein thrombosis, and hepatic
      infarction.

PMID- 9922186
TI  - Virtual endoscopic colonography based on 3D MRI.
AB  - BACKGROUND: To evaluate the potential of magnetic resonance colonography (MRC) in
      detecting colorectal mass lesions. METHODS: Twenty patients underwent MR imaging
      (MRI) before colonoscopy. The colon was filled with a gadolinium (0.5 mol):water
      mixture (1:100) under MRI control, and patients were imaged while breath-holding
      imaged with a three-dimensional spoiled gradient echo sequence in the prone and
      supine positions. Images were interactively analyzed based on the combination of
      multiplanar reconstruction and virtual colonoscopy by a radiologist blinded to
      colonoscopic findings and the patient's history. MRC interpretations were
      correlated with colonoscopic results. RESULTS: Polyps smaller than 5 mm could not
      be identified with MRC. The sensitivity for detecting polyps of 5-10 mm was 70%,
      whereas mass lesions larger than 10 mm were all detected (sensitivity = 100). The
      sensitivity, specificity, and accuracy for identifying polyp-positive patients
      including the three patients with small (<5 mm) polyps were 64%, 89%, and 75%,
      respectively. CONCLUSION: Virtual colonoscopy based on MRI data is feasible and
      should be evaluated in a larger sample of patients.

PMID- 9922187
TI  - Abdominal findings in AIDS-related pulmonary tuberculosis correlated with
      associated CD4 levels.
AB  - BACKGROUND: To document the abdominal manifestations of tuberculosis (TB)
      associated with human immunodeficiency virus (HIV) infection and to correlate
      those findings with CD4 levels. METHODS: Twenty-nine HIV-positive patients with
      culture-proven Mycobacterium tuberculosis infection were entered into the study.
      Chest changes were used to separate patients into two groups: those with and
      those without evidence of previous TB. All patients had standard chest
      radiographs, routine and high-resolution chest computed tomography (CT), and
      abdominal ultrasound examinations. Twenty-four patients had abdominal CT scans.
      RESULTS: The group of patients with no previous radiographic evidence of
      pulmonary TB had a significantly greater tendency to have manifestations of
      pulmonary and/or abdominal miliary dissemination. Those patients with
      radiological evidence of miliary dissemination were significantly more likely to
      have CD4 counts of less than 300. CONCLUSIONS: Chest and abdominal miliary
      dissemination of TB in HIV-positive patients is significantly associated with
      radiologically determined primary onset pulmonary TB. These changes occur
      predominantly at CD4 counts of less than 300.

PMID- 9922189
TI  - Metallic stenting of gastroduodenal and colonic stenoses.

PMID- 9922188
TI  - Abdominal findings in AIDS-related pulmonary tuberculosis correlated with
      associated CD4 levels.

PMID- 9922190
TI  - Sonographic and color Doppler findings of rupture of liver tumors.
AB  - We present six cases of ruptured liver tumor (hepatocellular carcinoma, five
      cases; liver metastasis, one case) in which gray-scale sonography revealed an
      ascites containing constantly moving dense high-echo spots, leading to a high
      suspicion of acutely developing hemoperitoneum. Color Doppler sonography helped
      in detecting the rupture site by demonstrating a high-velocity jet flow from it.
      Although four of six patients were dead within 3 months, detection of the rupture
      site by color Doppler sonography made the initial transarterial embolization
      therapy easy and prompt.

PMID- 9922191
TI  - MR imaging patterns of gadolinium retention within liver neoplasms.
AB  - BACKGROUND: To determine the spectrum of appearances of gadolinium retention
      within cholangiocarcinoma (CCA) and other liver neoplasms. METHODS: Two hundred
      ten patients underwent hepatic magnetic resonance imaging (MRI) at 1.5 T with
      precontrast T1- and T2-weighted spin-echo (SE) images and delayed Gd-DTPA- or
      gadoteridol- (0.1 mmol/kg) enhanced T1-weighted SE images. Postcontrast images
      were evaluated for lesions suspicious for tumors, and lesion signal intensity was
      characterized as homogeneously or heterogeneously hypo-, iso-, mildly hyper-, or
      markedly hyperintense to liver. Data from 94 patients with benign or malignant
      neoplasms are presented. RESULTS: Imaging demonstrated 237 malignant neoplasms
      (121 hepatocellular carcinoma [HCC], 26 CCA, 17 colon carcinoma metastases, 73
      other tumors) and 28 benign neoplasms (22 hemangioma, six focal nodular
      hyperplasia [FNH]). One hundred forty malignant lesions appeared as homogeneous
      postcontrast (29 hypointense, 75 isointense, 17 mildly hyperintense, 19 markedly
      hyperintense) and 97 as heterogeneous (15 isointense, 50 mildly hyperintense, 32
      markedly hyperintense). Malignant lesions showing homogeneous, mildly or markedly
      hyperintense signal intensity postcontrast included 10 CCA, seven HCC, six
      epithelioid hemangioendothelioma, eight neuroendocrine tumor metastases, three
      adenocarcinoma metastases of unknown origin, and one breast carcinoma metastasis.
      Hemangiomas appeared as homogeneous postcontrast in 19 lesions (six isointense,
      one mildly hyperintense, 12 markedly hyperintense) and as heterogeneous in three
      lesions (markedly hyperintense). FNH appeared as homogeneous postcontrast in one
      lesion (isointense) and as heterogeneous in five lesions (one isointense, four
      mildly hyperintense). CONCLUSION: Homogeneous gadolinium retention on delayed
      postcontrast images of malignant hepatic neoplasms is seen in a high percentage
      of CCA lesions and less commonly with other neoplasms.

PMID- 9922193
TI  - CT of agenesis and atrophy of the right hepatic lobe.
AB  - BACKGROUND: To identify and differentiate agenesis and severe atrophy of the
      right hepatic lobe on computed tomography (CT). METHODS: The CT examinations of
      three cases of agenesis and 11 cases of severe atrophy of the right hepatic lobe
      were reviewed. We evaluated visibility of the three hepatic veins, the two main
      portal veins (including their branches if necessary), the dilated intrahepatic
      ducts, enlargement of the medial and lateral segments of the left lobe and
      caudate lobe of the liver, presence of a retrohepatic gallbladder,
      hyperattenuation of the atrophic liver parenchyma, posterolateral interposition
      of the hepatic flexure of the colon, and upward migration of the right kidney.
      RESULTS: In the three cases of agenesis, no structure can be recognized as the
      right hepatic vein, right portal vein, or dilated right intrahepatic ducts. In
      the 11 cases of severe lobar atrophy, the right portal vein (or its branches) was
      recognized in eight cases, the right hepatic vein in four cases, and the dilated
      right intrahepatic ducts in 11 cases. The degree of enlargement of the lateral
      segment does not necessarily change inversely with the size of the medial segment
      and the caudate lobe. The retrohepatic gallbladder is present in eight cases (two
      in agenesis and six in atrophy). The phenomenon of hyperattenuation of the
      atrophic liver parenchyma was noted in six cases. CONCLUSION: Even though a
      retrohepatic gallbladder and a severely distorted hepatic morphology due to
      compensatory hypertrophy of the left and caudate lobes may raise a suspicion of
      agenesis of the right lobe of the liver, absence of visualization of all of the
      right hepatic vein, right portal vein and its branches, and dilated right
      intrahepatic ducts is a prerequisite of the diagnosis of agenesis of the right
      hepatic lobe on CT. In severe lobar atrophy, at least one of these structures is
      recognizable.

PMID- 9922192
TI  - Fluid-fluid levels in giant cavernous hemangioma of the liver: CT and MRI
      demonstration.
AB  - Fluid-fluid levels were observed in a case of giant cavernous hemangioma on
      computed tomography (CT) and magnetic resonance (MR) imaging. The fluid-fluid
      level may be attributed to the separation of blood cells and serous fluid due to
      the extremely slow flow in cavernous hemangioma of the liver.

PMID- 9922194
TI  - Fatal thrombosis of the portal vein following single-session percutaneous ethanol
      injection therapy of hepatocellular carcinoma.
AB  - Two weeks after percutaneous ethanol injection therapy for hepatocellular
      carcinoma, performed by injecting 110 mL ethanol in a single session with general
      anesthesia, a 69-year-old woman with well-compensated liver cirrhosis developed
      an extensive thrombosis of the whole portal tree that caused severe uncorrectable
      ascites and progressive deterioration of her general condition, resulting in
      death 6 weeks after the procedure.

PMID- 9922195
TI  - Cholangiographic appearance of bile-duct cysts.
AB  - Bile-duct cysts or congenital bile-duct dilatation are rare but important
      abnormalities often mimicking calculous biliary tract disease. Bile-duct cysts
      are most often classified according to Todani. In a retrospective study of
      percutaneous, peroperative or endoscopic cholangiograms from 25 patients,
      diagnosed and treated during a 20-year period, images of different types of bile
      duct cysts are presented and classified. The disease usually presents with vague
      symptoms and has a female preponderance. Current opinion on aetiology and
      complications is discussed. Cholangiography is a necessary prerequisite to
      surgical therapy.

PMID- 9922196
TI  - Choledochal cysts: evaluation with MR cholangiography.
AB  - BACKGROUND: To determine where magnetic resonance (MR) cholangiography can
      accurately demonstrate the presence, extent, and type of choledochal cysts.
      METHODS: Ten patients with sonographically suspected choledochal cysts were
      evaluated with a non-breath-hold MR cholangiography technique. The presence,
      extent, and type of choledochal cyst were determined. Visualization of the
      pancreatobiliary junction was recorded. MR cholangiographic findings were
      correlated with the gold standard of surgery in six patients, endoscopic
      retrograde cholangiography in two, and a 99mTc hepatobiliary scintigram in one.
      Three patients underwent intraoperative cholangiography. RESULTS: All MR
      cholangiograms were correlated with findings at surgery, endoscopic retrograde
      cholangiography, or 99mTc hepatobiliary scintigraphy. There were seven Todani
      type 1 and two Todani type 5 choledochal cysts (Caroli's disease). The extent of
      involvement was correctly demonstrated on all MR cholangiograms. The
      pancreatobiliary junction could not be identified in any of the cases. Calculi
      and sludge were correctly identified on the MR cross-sectional images in three
      patients but were not seen on MR cholangiograms in two. In one patient with an
      initially misinterpreted choledochal cyst, MR sectional images showed the typical
      appearance of a hydatid cyst, which was confirmed at surgery. CONCLUSION: MR
      cholangiography can be used to confirm the diagnosis of choledochal cysts and
      define the extent of involvement preoperatively. The pancreatobiliary junction,
      however, is difficult to visualize. Non-biliary cysts such as a hydatid cyst can
      mimic a choledochal cyst on the MR cholangiogram and should be correlated with
      the MR cross-sectional images to avoid misinterpretation.

PMID- 9922197
TI  - Cholangiographic demonstration of the cholecystohepatic duct of Luschka.
AB  - The cholecystohepatic duct of Luschka is demonstrated. This anomaly directly
      connects the gallbladder to the bile ducts, draining a portion of the right lobe
      of the liver. The pertinent embryology is reviewed. When accidentally severed, it
      may cause a bile leak leading to biloma formation. It should be recognized before
      surgery to alert the surgeon.

PMID- 9922198
TI  - Added value of CT criteria compared to the clinical SAP score in patients with
      acute pancreatitis.
AB  - BACKGROUND: To assess the added value of established computed tomography (CT)
      scores versus the Simplified Acute Physiology (SAP) score in predicting outcome
      in patients with acute pancreatitis. METHODS: Contrast-enhanced CT was performed
      in 45 patients with acute pancreatitis. The Balthazar score, CT severity index
      (CTSI), and Schroder score were assessed, and the SAP score was calculated. The
      predictive values of CT score and SAP score for mortality, need for one or more
      interventions, and length of hospital stay were compared. The added value of the
      SAP score to the CT scores was assessed by using ROC (receiver operating curve)
      analysis. RESULTS: The positive predictive values of the higher Balthazar, CTSI,
      Schroder, and SAP scores, reflecting severe disease, were 50%, 41%, 41%, and 48%,
      respectively, for mortality, 85%, 84%, 84%, and 83%, respectively, for need for
      one or more interventions, and 55%, 66%, 66%, and 65%, respectively, for longer
      hospital stay. The negative predictive values of the lower Balthazar, CTSI,
      Schroder and SAP scores were 84%, 92%, 92%, and 42%, respectively, for mortality,
      44%, 69%, 69%, and 45%, respectively, for need for one or more interventions, and
      44%, 69%, 69%, and 55%, respectively, for longer hospital stay. When CT scores
      were added to the SAP score, there was no improvement in discriminating power for
      mortality. CONCLUSION: To identify patients with severe outcome, there is no
      clear benefit using established CT scores as opposed to the SAP score. However,
      the Balthazar score and CTSI are better than the SAP score in predicting a
      favorable outcome.

PMID- 9922199
TI  - Splenic artery aneurysm: value of color Doppler and the limitation of gray-scale
      ultrasonography.
AB  - BACKGROUND: To reevaluate the advantages and limitations of gray-scale and color
      Doppler sonography in the diagnosis of splenic artery (Sp-A) aneurysm. METHODS:
      We reviewed the gray-scale and color Doppler sonograms of five cases with Sp-A
      aneurysm (four patients with portal hypertension and one patient without portal
      hypertension). Color Doppler sonography was performed in all five patients, and
      power Doppler sonography was performed in three. RESULTS: Gray-scale sonography
      failed to detect the aneurysm in four of five cases because of a surrounding
      splenorenal (Sp-R) shunt in three patients and marked calcification of the
      aneurysmal wall in one patient. Pulsed Doppler sonography showed a slightly
      turbulent pulsatile flow along the aneurysmal wall, which immediately led to the
      diagnosis in four cases, including the three cases with Sp-R shunt. In one case,
      color Doppler sonography failed to detect the aneurysm because of a markedly
      calcified aneurysmal wall, although power Doppler sonography could visualize the
      aneurysm. CONCLUSIONS: Gray-scale sonography is not a useful diagnostic tool for
      Sp-A aneurysm. Clinicians should use color Doppler sonography in the evaluation
      of the splenic hilus in patients with Sp-R shunt to find a small Sp-A aneurysm.
      The addition of power Doppler sonography is helpful in visualizing calcified Sp-A
      aneurysms.

PMID- 9922200
TI  - Littoral cell angioma of the spleen.
AB  - Littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. LCA
      most commonly presents with constitutional symptoms (low grade fever and fatigue)
      and signs of hypersplenism (anemia and thrombocytopenia). Radiographically and at
      gross pathology an enlarged spleen containing multiple nodules is most commonly
      seen. Currently the radiological findings are nonspecific and correlation with
      clinical findings is necessary to narrow the differential while tissue is
      required for a definitive diagnosis.

PMID- 9922201
TI  - Littoral cell angioma of the spleen: US and MR imaging findings.
AB  - In this article, we describe the ultrasound and magnetic resonance imaging
      findings of a littoral cell angioma of the spleen. This benign vascular neoplasm
      of the spleen has been described, but to our knowledge there has been no case
      published in the literature that describes its imaging features.

PMID- 9922202
TI  - Leiomyomatosis peritonealis disseminata complicated by sarcomatous transformation
      and ovarian torsion: presentation of two cases and review of the literature.
AB  - Leiomyomatosis peritonealis disseminata (LPD) is a rare disorder usually
      discovered incidentally in women of child-bearing age and is characterized by
      multiple subperitoneal smooth muscle nodules. Case reports of two patients with
      complications related to LPD and a review of the literature are presented. In one
      case, the patient carried the diagnosis of LPD for 11 years and experienced
      sarcomatous transformation; this is the first report of the magnetic resonance
      appearance of this entity. In the second case, LPD was diagnosed after an LPD
      implant on the ovary-induced ovarian torsion. We also present a patient in whom
      large, pedunculated uterine leiomyomas mimicked LPD. The clinical presentation,
      possible pathogenesis, imaging features, and therapeutic options of LPD are
      reviewed. Because this uncommon condition is being reported with increasing
      frequency, familiarity with its imaging features and pitfalls is important to
      suggest the diagnosis in the appropriate clinical setting.

PMID- 9922203
TI  - Infected abdominal aortic aneurysm: early CT findings.
AB  - We describe computed tomographic (CT) findings at the early stage of infected
      abdominal aortic aneurysm in three patients. Periaortic mass and increased fat
      density were the characteristic findings of early aortic infection on CT. Similar
      findings caused by other diseases may be difficult to differentiate by imaging
      alone, but these findings should be used to trigger close follow-up for patients
      with suspected infected abdominal aortic aneurysm.

PMID- 9922204
TI  - Renal medullary cystic disease: assessment by MRI.
AB  - Medullary cystic disease is an important cause of renal failure in adolescent
      patients. Imaging plays a primary role in the diagnosis of this entity as cysts
      are characteristically seen in the renal medulla and corticomedullary junction
      with normal to small sized kidneys. Imaging studies that do not use intravenous
      contrast or ionizing radiation are particularly useful given the young age of
      these patients and presence of renal failure. In this case, we demonstrate the
      imaging findings of medullary cystic disease by MRI.

PMID- 9922205
TI  - Struma ovarii: appearance on MR images.
AB  - BACKGROUND: The purpose of this multi-institutional study was to examine the
      appearance of struma ovarii on magnetic resonance (MR) images. METHODS: MR images
      of 12 patients with histologically proven struma ovarii were retrospectively
      reviewed. All patients underwent T1-weighted and T2-weighted imaging. Contrast
      enhanced T1-weighted images with Gd-DTPA were available in 10 patients. The
      following determinations were made: tumor morphology, signal intensities,
      contrast-enhancement effects of solid components with Gd-DTPA, and comparison of
      MR images with resected specimens. RESULTS: All 12 patients had both cystic and
      solid components, with a multilobulated surface and thickened septa. Signal
      intensities on T1-weighted images were mainly low, partly intermediate to high,
      or high, and those on T2-weighted images were mainly high, with different signal
      intensities. Contrast-enhancement effects were marked or moderate. The contents
      that showed low signal intensities on T1-weighted images and signal voids or low
      signal intensities on T2-weighted images were viscid gelatinous materials.
      CONCLUSIONS: A multicystic tumor with a solid component, a multilobulated
      surface, and signal intensities that indicate the presence of viscid gelatinous
      materials appear to be a characteristic MR finding of struma ovarii.

PMID- 9922206
TI  - Ovarian fibroma of high signal intensity on T2-weighted MR image.
AB  - It has been reported that ovarian fibromas display low signal intensity on both
      T1- and T2-weighted magnetic resonance images. We report an ovarian fibroma
      exhibiting low signal intensity on a T1-weighted image and high signal intensity
      on a T2-weighted image. Microscopically pronounced myxomatous changes were shown
      in the fibroma. The signal intensity of ovarian fibromas differs with the degree
      of myxomatous change.

PMID- 9922207
TI  - Subphrenic crescentic lucencies: pneumoperitoneum vs extraperitoneal air.

PMID- 9922208
TI  - Proliferation and differentiation defects during lung development in
      corticotropin-releasing hormone-deficient mice.
AB  - Corticotropin-releasing hormone-deficient (CRH-KO) mice, which as a consequence
      are also glucocorticoid-insufficient, exhibit neonatal lethality when derived
      from CRH-KO mothers. Death is due to respiratory insufficiency as a result of
      abnormal pulmonary development, and can be prevented by prenatal administration
      of glucocorticoids. In the study described here, we used CRH-KO mice as a model
      of genetically altered in utero glucocorticoid action to elucidate the role of
      endogenous glucocorticoids in lung maturation. The histologic appearance of the
      lungs of these mice is normal until Day 17.5 of gestation, at which point failure
      of septal thinning and air-space formation is observed. These morphologic
      alterations in the CRH-KO mouse lung are the result of continued cell division in
      cellular compartments that by this time in gestation have ceased proliferating in
      wild-type mice, rather than the result of a failure of apoptosis. In accord with
      this observation, the CRH-KO lung exhibits delayed induction of type II
      pneumocyte biochemical parameters, such as messenger RNAs (mRNAs) for surfactant
      protein-A (SP-A) and SP-B, and fatty acid synthase, as well as delayed Clara cell
      maturation. In contrast, surfactant phospholipid synthesis is not impaired during
      CRH-KO lung development. Our findings indicate that an essential role of
      endogenous glucocorticoids in pulmonary maturation in utero is to stimulate a
      developmental program in late gestation that affects epithelial and mesenchymal
      cell proliferation and differentiation throughout the parenchyma.

PMID- 9922209
TI  - Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the
      airways through nuclear factor-kappaB activation and IL-8 mRNA expression in
      guinea pigs in vivo.
AB  - We examined the hypothesis that superoxide mediates infiltration of neutrophils
      to the airways through nuclear factor (NF)-kappaB and interleukin-8 (IL-8) after
      acute exposure to cigarette smoke (CS) in vivo. Male Hartley strain guinea pigs
      were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The
      differential cell count of bronchoalveolar lavage fluid and specific
      myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused
      neutrophil accumulation to the airways and parenchyma, respectively. Acute
      exposure to CS increased DNA-binding activity of NF-kappaB in the lung. Acute
      exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung.
      Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD)
      aerosols reduced the CS-induced neutrophil accumulation to the airways. Both
      activation of NF-kappaB and increased IL-8 mRNA expression were also inhibited by
      the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50
      were detected in the nuclei of alveolar macrophages after acute exposure to CS.
      The signal for IL-8 mRNA expression was demonstrated in the alveolar space after
      acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor
      IL-8 mRNA signals were observed in airway epithelium. These observations suggest
      that acute exposure to CS initiates superoxide-dependent mechanism that, through
      NF-kappaB activation and IL-8 mRNA expression, produces infiltration of
      neutrophils to the airways in vivo. It was also suggested that the alveolar
      macrophage is one potential source of NF-kappaB activation and IL-8 mRNA
      expression after acute exposure to CS.

PMID- 9922210
TI  - Elevated levels of the IGF-binding protein protease MMP-1 in asthmatic airway
      smooth muscle.
AB  - We have previously demonstrated that the asthma-associated proinflammatory
      eicosanoid leukotriene D4 (LTD4) is co-mitogenic with insulin-like growth factors
      (IGFs) in airway smooth-muscle (ASM) cells in vitro. This synergistic effect of
      LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced IGF binding
      proteins (IGFBPs), which are cell growth-inhibitory proteins. We also identified
      this IGFBP protease to be the matrix metalloproteinase-1 (MMP-1), and showed that
      this enzyme had a significant role in modulating IGF action in ASM cells. In the
      present study, we tested the hypothesis that ASM hyperplasia in vivo involves
      induction of MMP-1 leading to IGFBP proteolysis. We detected the presence of MMP
      1 and measured its levels in human airway tissue sections prepared from
      nonasthmatic and asthmatic subjects. Six nonasthmatic and six asthmatic airway
      tissue samples were analyzed for immunoreactive MMP-1 through an
      immunohistochemical detection method. Both the bronchial and tracheal smooth
      muscle cells from different regions of the same sample were examined and
      documented. The immunostaining for MMP-1 was significantly elevated in both the
      bronchial and tracheal smooth-muscle cells of the airway sections from asthmatic
      samples relative to that of the nonasthmatic samples. The differences in levels
      of MMP-1, IGFBP-2, IGFBP-3, and IGFBP proteolytic activity were quantified using
      densitometric analyses of the ASM tissue extracts that were separated on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The MMP-1 levels in the
      asthmatic airway tissue extracts were 12-fold higher than those found in control
      samples. In addition, IGFBP-2 and IGFBP-3, which we have previously demonstrated
      to be proteolytic substrates of MMP-1, were found to be cleaved in asthmatic
      airway tissue extracts. Furthermore, the asthmatic airway extracts contained
      IGFBP proteolytic activity that was shown by immunodepletion studies to be due to
      MMP-1. These observations demonstrate that MMP-1 may play a significant role in
      inducing ASM hyperplasia and airway obstruction in asthma by modulating the IGF
      axis.

PMID- 9922211
TI  - Developmental mucin gene expression in the human respiratory tract.
AB  - The epithelial surface of the respiratory tract is coated with a protective film
      of mucus secreted by epithelial goblet and submucosal gland cells. Histology of
      the airway mucosa and composition of secretions during the second trimester of
      fetal life are known to differ from the normal adult in that these secretions
      show similarities with those of hypersecretory disorders. To provide information
      regarding cell-specific expression of mucin genes and their relation to
      developmental patterns of epithelial cytodifferentiation, we studied the
      expression of eight different mucin genes (MUC1-MUC4, MUC5AC, MUC5B, MUC6, MUC7)
      in human embryonic and fetal respiratory tract using in situ hybridization. These
      investigations demonstrated that MUC4 is the earliest gene expressed in the
      foregut at 6.5 wk, followed by MUC1 and MUC2 from 9. 5 wk of gestation in
      trachea, bronchi, epithelial tubules, and terminal sacs before epithelial
      cytodifferentiation. In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later
      gestational ages concomitant with epithelial cytodifferentiation. During this
      developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated
      cells, whereas MUC2 mRNAs are located in basal and goblet cells. MUC5AC
      expression is confined to goblet cells. In the submucosal glands, MUC2 mRNAs are
      located in both mucous and serous cells, whereas MUC5B and MUC7 mRNAs are
      expressed in mucous and in serous cells, respectively. These data suggest
      distinct developmental roles for MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the
      elongation, branching, and epithelial cytodifferentiation of the respiratory
      tract during ontogenesis. Distinct patterns of mucin gene expression are also
      likely to play an important role in regulating appropriate epithelial cell
      proliferation and cytodifferentiation in adult airway mucosa as it is indicated
      by aberrant expression in hypersecretory disorders.

PMID- 9922212
TI  - Brief exposure to 95% oxygen alters surfactant protein D and mRNA in adult rat
      alveolar and bronchiolar epithelium.
AB  - Surfactant protein D (SP-D), which has structural homology to C-type lectin
      binding regions, may play a role in host defense and has no known surfactant
      function. Because other surfactant proteins have been shown to be increased after
      prolonged periods of hyperoxia, we sought to evaluate the early effects of
      hyperoxia (95% O2) on expression of SP-D in the adult male rat lung. Animals were
      exposed to air or to 12, 36, or 60 h of 95% O2. Northern blot analysis of total
      lung RNA revealed marked SP-D mRNA increases at 12 h 95% O2 compared with air
      exposed controls, with decreasing expression to near that of air-exposed animals
      by 60 h. Semiquantitative in situ RNA hybridization demonstrated parallel
      results, with increased numbers of labeled alveolar epithelial (AE) and
      bronchiolar epithelial (BE) cells at 12 h and increased intensity of labeled
      alveolar cells, compared with air-exposed controls. After 60 h of exposure to 95%
      O2, mRNA label intensity in AE and BE was decreased to levels near those seen in
      air-exposed animals. In contrast, Western blotting showed a decline in total lung
      SP-D with 95% O2 exposure, beginning at 12 h and continuing at 36 and 60 h,
      respectively. Semiquantitative immunohistochemistry demonstrated a decline in AE
      labeling parallel to the total lung Western blot results, but labeled total BE
      cell numbers increased (P = 0.10). Hyperoxia had differential effects on SP-D
      abundance in AE and BE cells, and therefore may influence the availability of SP
      D to bind microbial pathogens in the airways depending on cell type and location.

PMID- 9922213
TI  - Lung fibroblasts undergo apoptosis following alveolarization.
AB  - In the rat lung, primary saccules are transformed into alveoli from postnatal
      Days 4 to 13, after which time there is a 20% reduction in the number of lung
      fibroblasts as the interstitial volume of the alveolar walls decreases. Our
      objective was to determine whether apoptosis is a factor in the observed decrease
      in the number of interstitial lung fibroblasts beyond Day 13. We used both
      histologic and flow cytometric assays to detect in lung fibroblasts the DNA
      fragmentation and condensation that are characteristic of apoptosis. In addition,
      we evaluated levels of bcl-2 and BAX messenger RNAs (mRNAs) using a reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay. Apoptotic cells were
      quantitated in glycol methacrylate-embedded sections of neonatal rat lungs using
      the terminal transferase dUTP-digoxygenin nick end-labeling (TUNEL) method.
      Although TUNEL-positive interstitial cells were observed in the lungs of rats
      ranging in age from 10 to 16 d, a dramatic increase in apoptotic cells was seen
      on Day 17. Although diminished in number, TUNEL-positive cells were still present
      on Day 28. Hoechst-stained apoptotic bodies were observed in isolated lung cells
      that were vimentin-positive and factor VIII-negative, which identified the
      apoptotic cells as fibroblasts as opposed to endothelial cells. Flow cytometric
      analysis of freshly isolated lung fibroblasts stained with Hoechst 33342
      indicated a 24% increase in chromatin condensation in cells from 17-d versus 16-d
      rats. DNA fragmentation was also quantitated by flow cytometry in freshly
      isolated fibroblasts labeled with BODIPY-conjugated dUTP in the presence of
      terminal deoxynucleotidyl transferase. The percentage of lung fibroblasts
      containing fragmented DNA was 51.4 +/- 13.4 in 17-d, 36.9 +/- 8.6 in 18-d, and
      13.8 +/- 5.4 in 19-d rat pups. Finally, evaluation by RT-PCR indicated that on
      postnatal Day 17, mRNA for bcl-2, which inhibits apoptosis, was decreased to 73.5
      +/- 11.4% (P < 0.001) of Day 5 controls; whereas mRNA for BAX, which enhances
      apoptosis, was increased to 243.0 +/- 102.0% (P < 0.001) of Day 5 values. These
      results demonstrate that rat lung fibroblasts undergo apoptosis after the
      completion of alveolarization, and suggest that this decrease in fibroblast
      number plays an important role in the thinning and remodeling of the alveolar
      walls of the lung.

PMID- 9922214
TI  - Tissue macrophages associated with angiogenesis in chronic airway inflammation in
      rats.
AB  - Angiogenesis is a feature of chronic inflammation produced by Mycoplasma pulmonis
      infection of the respiratory tract. The mechanism of this angiogenesis is
      unknown, but cellular growth factors and matrix remodeling proteases produced by
      inflammatory cells are likely to be involved. The goal of this study was to
      determine the relationship between changes in the number, shape, and distribution
      of ED2-immunoreactive macrophages and the development of angiogenesis in the
      tracheal mucosa of Wistar rats after M. pulmonis infection. In pathogen-free
      rats, ED2-positive cells were scattered in the airway mucosa (261 +/- 42
      cells/mm2 of surface, mean +/- SE). Most cells were irregularly shaped and had
      moderate ED2 immunoreactivity. No lymphoid tissue was present. The number of ED2
      positive cells increased rapidly after infection, was 120% above baseline at 1
      wk, and remained significantly increased throughout the 4-wk study (P < 0.05).
      Angiogenesis was first detected at 2 wk, and at 3 wk the vessel length density
      was nearly 8-fold the pathogen-free value. At 3 and 4 wk, focal sites of
      angiogenesis coincided with discrete clusters of round, strongly immunoreactive
      ED2-positive cells (1,340 +/- 124 cells/mm2) in polyp-like collections of mucosal
      lymphoid tissue. The close association of distinctive ED2-positive cells with
      angiogenic blood vessels suggests a relationship between a subset of tissue
      macrophages and the angiogenesis associated with M. pulmonis infection. The time
      course of the changes indicates that the initial influx of ED2-positive
      macrophages precedes the angiogenesis, and the rounding of the cells parallels
      the growth of new vessels.

PMID- 9922215
TI  - Effects of chronic anti-interleukin-5 monoclonal antibody treatment in a murine
      model of pulmonary inflammation.
AB  - The maturation of eosinophils in bone marrow, their migration to pulmonary
      tissue, and their subsequent degranulation and release of toxic granule proteins
      contributes to the pathophysiology observed in asthma. Interleukin-5 (IL-5) is
      essential for these processes to occur. Therefore, much emphasis has been placed
      on attempts to inhibit the production or activity of IL-5 in order to attenuate
      the inflammatory aspect of asthma. In this report, the immunological consequences
      of long-term exposure to an antibody recognizing IL-5 (TRFK-5) were studied in a
      murine pulmonary inflammation model. A single dose of TRFK-5 (1 mg/ kg,
      intraperitoneally) reversibly inhibited antigen-dependent lung eosinophilia in
      mice for at least 12 wk and inhibited the release of eosinophils from bone marrow
      for at least 8 wk. Normal responses to aerosol challenge were attained after 24
      wk. In mice treated acutely with antibody (2 h before challenge), 50% inhibition
      of pulmonary eosinophilia occurred when 0. 06 mg/kg TRFK-5 was administered
      (intraperitoneally; ED50), resulting in 230 ng/ml (IC50) in serum. In mice
      treated with one dose of TRFK-5 (1 mg/kg) and rested before challenge, the
      antibody exhibited a half-life of 2.4 wk. After 18 to 19 wk, antigen challenge
      induced eosinophilia was inhibited by 50% and serum levels of TRFK-5 were 25
      ng/ml. TRFK-5 remaining in mice 8 wk after a single injection of TRFK-5 was
      sufficient to inhibit at least 50% of the eosinophilia induced in blood 3 h after
      injection of recombinant murine IL-5 (10 microg/kg, intravenously). To assess the
      biologic effect of long-term exposure of mice to antibody, several parameters of
      immune-cell function were measured. Throughout the extended period of activity of
      TRFK-5 (>/= 12 wk) there were no gross effects on antigen-dependent increases in
      T-cell recruitment into bronchoalveolar fluid (BALF), in IL-4 and IL-5 steady
      state mRNA levels in lung tissue, or in immunoglobulin E (IgE) and IgG levels in
      serum. There was a small increase in IL-5 steady-state mRNA production in TRFK-5
      treated mice after 2 h or 2 wk, but this was not observed at other times
      examined. In untreated mice, IL-5 steady-state mRNA production in response to
      antigen challenge decreased > 6-fold with age, although at all time points there
      was an increase in mRNA levels following challenge. Therefore, at later times, 25
      ng/ml rather than 230 ng/ml of TRFK-5 inhibited BALF eosinophilia, probably
      because of reduced IL-5 levels. Twenty-four weeks after treatment with TRFK-5,
      when challenge-induced eosinophilia was restored, there was an excess of CD4(+) T
      cells in BALF from challenged mice. However, these T cells had no measurable
      effects on other responses to challenge, including cytokine production, B-cell
      accumulation, and immunoglobulin production in serum. Thus, the biologic duration
      of TRFK-5 was several months, and its activity was due to the presence of
      antibody above a therapeutic threshold rather than to any profound effect on the
      immune system.

PMID- 9922216
TI  - Gene transfer of mitochondrially targeted glutathione reductase protects H441
      cells from t-butyl hydroperoxide-induced oxidant stresses.
AB  - Increased generation of reactive oxygen species (ROS) and low levels of
      antioxidants may cause morbidity in premature infants on supplemental oxygen.
      Glutathione (GSH)-dependent antioxidant systems protect against ROS, and
      regenerating GSH from GSH disulfide (GSSG) by the flavoenzyme GSH reductase (GR)
      is essential for the optimal function of this system. Previously, we have
      observed enhanced resistance to t-butyl hydroperoxide (t-BuOOH) in Chinese
      hamster ovary cells stably transfected with a vector (leader sequence GR [LGR])
      for human GR cDNA that contained a functional synthetic mitochondrial targeting
      signal. The present studies were designed to investigate adenovirus-mediated gene
      transfer of LGR to H441 cells and resistance of such cells to t-BuOOH. Adenovirus
      mediated transfection of H441 cells with LGR increased total GR activities more
      than 11-fold (mitochondria more than 10-fold and cytosolic more than 7-fold) and
      protected against t-BuOOH cytotoxicity, as indicated by lower fractional release
      of cellular lactate dehydrogenase (LDH) than was observed in wild-type
      untransfected cells (CON) or in cells transfected with a control gene (human
      manganese superoxide dismutase in the antisense orientation [DOS]) (*LGR 6.6 +/-
      1.7; DOS 16 +/- 1.8; CON 16.6 +/- 0.7% LDH release). In addition, cells
      transfected with LGR retained higher GSH/GSSG ratios (*LGR 66 +/- 0.4; DOS 47 +/-
      1; CON 52.6 +/- 2.3) and released less GSH + GSSG to the media in response to
      challenge with t-BuOOH (*LGR 0.05 +/- 0.01; DOS 0.08 +/- 0.01; CON 0.07 +/- 0.01
      nmol/mg of protein) than did wild-type cells or cells transfected with a control
      vector, indicating an enhanced ability of the LGR cells to reduce GSSG formed in
      response to exposure to t-BuOOH. In conclusion, adenovirus-mediated gene transfer
      of LGR enhanced cellular GR activities and protected H441 cells from oxidant
      stresses.

PMID- 9922217
TI  - Neutrophil influx into the lungs of beige mice is followed by elastolytic damage
      and emphysema.
AB  - The beige mouse is currently used as a model of elastase and cathepsin G
      deficiency to demonstrate or exclude the role of these proteases in a variety of
      pathologic conditions. We recently demonstrated that beige cathepsin G is tightly
      bound to neutrophil lysosomal membranes but is released in near normal quantities
      during exocytosis. Also, beige neutrophils contain a latent form of elastase that
      undergoes spontaneous activation when released under in vitro or in vivo
      conditions. However, the pathogenic potential of this enzyme in matrix
      degradation has not been ascertained previously. The possibility that in beige
      mice elastolytic proteases from neutrophils recruited into the lung have the
      capability to damage alveolar septa was investigated following an intratracheal
      instillation of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (200 microg).
      Neutrophil influx was followed by a decrease in lung elastin content (-18%) and
      by a significant increase of the mean linear intercept (+30%) and of morphologic
      emphysema. The onset of pulmonary lesion was preceded by a marked increase of
      neutrophil elastase burden on the alveolar interstitium. The appearance of
      emphysema was prevented by administration of the serine protease inhibitor 4-(2
      aminoetyl)-benzenesulfonyl fluoride hydrochloride (2. 4 microg/ml saline). These
      results demonstrate that the lung elastin degradation and emphysema can occur in
      beige lungs. The fact that the beige mouse does develop lung elastolytic changes
      after neutrophil recruitment indicates that this mutant cannot be considered a
      model of neutrophil function deficiency and used as a model of elastase
      deficiency.

PMID- 9922218
TI  - Interleukin-12 production by human alveolar macrophages is controlled by the
      autocrine production of interleukin-10.
AB  - By releasing interleukin (IL)-12 in the lung, alveolar macrophages (AM) may
      profoundly modify an immune response. The autocrine regulation of the
      heterodimeric, biologically active form of IL-12 (IL-12 p70) by IL-10 was
      studied, as well as the expression of its subunits of 35 kD (p35) and 40 kD
      (p40). AM cultured in medium alone expressed only p35 mRNA. Both p35 and p40 mRNA
      levels were induced by lipopolysaccharide (LPS) and were further increased by
      interferon-gamma (IFN-gamma). LPS alone induced IL-12 p40 but not IL-12 p70
      production in monocytes and in AM. However, IL-12 p70 was released when the
      autocrine production of IL-10 was neutralized by IL-10 blocking antibody, and IL
      12 p40 production increased. Although IFN-gamma markedly decreased LPS-induced IL
      10 production in AM, neutralizing IL-10 further enhanced the level of LPS and IFN
      gamma-induced IL-12 p70 in AM. In contrast, neutralizing the trace amount of IL
      10 released by AM stimulated by CD40 crosslinking and IFN-gamma did not increase
      IL-12 p70. Thus, IL-12 p70 production by AM appears to be tightly controlled by
      the autocrine release of IL-10 when stimulated by LPS, or by LPS and IFN-gamma,
      whereas CD40 crosslinking triggered IL-12 p70 production in the absence of
      autocrine regulation by IL-10.

PMID- 9922219
TI  - Surfactant protein-A binds group B streptococcus enhancing phagocytosis and
      clearance from lungs of surfactant protein-A-deficient mice.
AB  - Surfactant protein-A (SP-A) gene-targeted mice clear group B streptococcus (GBS)
      from the lungs at a slower rate than wild-type mice. To determine mechanisms by
      which SP-A enhances pulmonary clearance of GBS, the role of SP-A in binding and
      phagocytosis of GBS was assessed in SP-A (-/-) mice infected with GBS in the
      presence and absence of exogenous SP-A. Coadministration of GBS with exogenous SP
      A decreased GBS colony counts in lung homogenates of SP-A (-/-) mice. SP-A bound
      to GBS in a calcium-dependent manner. Although pulmonary infiltration with
      macrophages was not altered in SP-A (-/-) versus wild-type mice after GBS
      infection, the number of alveolar macrophages with phagocytosed bacteria was
      lower in the SP-A (-/-) mice than in the wild-type mice. When SP-A was
      coadministered with GBS, phagocytosis was significantly increased. Oxygen radical
      production by alveolar macrophages from SP-A (-/-) mice infected with GBS was
      decreased compared with wild-type controls and was increased when SP-A (-/-) mice
      were infected in the presence of exogenous SP-A. Superoxide (SO) radical
      generation was deficient in macrophages from SP-A (-/-) mice. SP-A plays an
      important role in GBS clearance in vivo, mediated in part by binding to and
      enhancing GBS phagocytosis and by increasing SO production by alveolar
      macrophages.

PMID- 9922220
TI  - Z and S mutations of the alpha1-antitrypsin gene and the risk of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) has been associated with
      heterozygosity for the Z and S alleles of the alpha1-antitrypsin gene in some
      studies, but these observations have not been confirmed by others. Cigarette
      smoking is the major risk factor for COPD and may have been a confounding factor
      in many of the previous studies. We investigated whether the Z or S alleles were
      more prevalent in a group of heavy smokers with COPD than in a group of
      nonobstructed smokers. Forced expiratory volume in 1 s and forced vital capacity
      were derived for 266 patients undergoing lobar or lung resection. These lung
      function measurements were used to divide the patients into a COPD group and a
      group of nonobstructed control subjects. The subjects were typed for the Z and S
      alleles of the alpha1-antitrypsin gene using a polymerase chain reaction-based
      technique. In the COPD patients, 12 of 193 (6%) were heterozygous for the Z
      allele (MZ) compared with 0 of 73 control subjects, which gave a P value of 0.04
      after correction for age, gender, and smoking history. There was no association
      of the S allele with COPD. The results indicate that the Z, but not the S, allele
      is a risk factor for COPD in the heterozygous state.

PMID- 9922221
TI  - Identification and function of cyclic nucleotide phosphodiesterase isoenzymes in
      airway epithelial cells.
AB  - Epithelial cells actively participate in inflammatory airway disease by
      liberating mediators such as arachidonate metabolites and cytokines. Inhibition
      of phosphodiesterases (PDEs) may be a useful anti-inflammatory approach. The PDE
      isoenzyme pattern and the effects of PDE inhibition on mediator generation were
      analyzed in primary cultures of human and porcine airway epithelial cells (AEC)
      and in the bronchial epithelial cell line BEAS-2B. PDE4 and PDE5 were detected in
      lysates of all cell types studied. In primary cultures of human AEC, the PDE4
      variants PDE4A5, PDE4C1, PDE4D2, and PDE4D3 were identified by polymerase chain
      reaction analysis. Evidence of the recently described PDE7 was obtained by
      rolipram- insensitive cyclic adenosine monophosphate (cAMP) degradation, and its
      presence was verified by the demonstration of PDE7 messenger RNA. Primary
      cultures of human airway epithelium also expressed PDE1. Enhanced epithelial cAMP
      levels, induced by forskolin and PDE4 inhibition, increased formation of
      prostaglandin E2 (PGE2), but not of interleukin (IL)-8 or 15
      hydroxyeicosatetraenoic acid (15-HETE) in airway epithelial cells. Increased
      cyclic guanosine monophosphate levels in these cells provoked by sodium
      nitroprusside and the PDE5 inhibitor zaprinast reduced the PGE2 synthesis,
      whereas 15-HETE and IL-8 formation were unchanged. The data suggest that PDE
      isoenzymes are important in airway inflammation and that PDE inhibitors exert
      anti-inflammatory effects by acting on AEC.

PMID- 9922222
TI  - Centriacinar remodeling and sustained procollagen gene expression after exposure
      to ozone and nitrogen dioxide.
AB  - Sprague-Dawley rats were exposed to 0.8 ppm ozone (O3), to 14.4 ppm nitrogen
      dioxide (NO2), or to both gases simultaneously for 6 h per day for up to 90 d.
      The extent of histopathologic changes within the central acinus of the lungs was
      compared after 7 or 78 to 90 d of exposure using morphometric analysis by
      placement of concentric arcs radiating outward from a single reference point at
      the level of the bronchiole- alveolar duct junction. Lesions in the lungs of rats
      exposed to the mixture of gases extended approximately twice as far into the
      acinus as in those exposed to each individual gas. The extent of tissue
      involvement was the same at 78 to 90 d as noted at 7 d in all exposure groups. At
      the end of exposure, in situ hybridization for procollagen types I and III
      demonstrated high levels of messenger RNA within central acini in the lungs of
      animals exposed to the combination of O3 and NO2. In contrast, animals exposed to
      each individual gas had a similar pattern of message expression compared with
      that seen in control animals, although centriacinar histologic changes were still
      significantly different from control animals. We conclude that the progressive
      pulmonary fibrosis that occurs in rats exposed to the combination of O3 and NO2
      is due to sustained, elevated expression of the genes for procollagen types I and
      III. This effect at the gene level is correlated with the more severe histologic
      lesions seen in animals exposed to both O3 and NO2 compared with those exposed to
      each individual gas. In contrast, the sustained expression of the procollagen
      genes is not associated with a shift in the distribution of the lesions because
      the area of change in each group after 7 d of exposure was the same as after 78
      to 90 d of exposure.

PMID- 9922223
TI  - In vitro reconstitution of the tracheal epithelium.
AB  - We have developed a unique in vitro reconstitution system for tracheal epithelia
      of guinea pigs. In the system, a human amnion membrane was used as a basement
      membrane and the tracheal epithelial cells were cultured on the epithelial side
      of the membrane. Three weeks later, the tracheal fibroblasts were co-cultured on
      the serosal side of the amnion membrane and the culturing was continued for an
      additional 10 d. The morphology of the cultured epithelial cells consisted of a
      pseudostratified columnar ciliated epithelium from cuboidal ciliated epithelium
      during the last 10 d of the culture period. Epithelial cells included both goblet
      like and basal cells. In addition, the frequency of each type of differentiated
      cells was almost identical to that of in vivo tracheas. Interestingly, the same
      results were obtained when the conditioned medium of the tracheal fibroblasts was
      used instead of the fibroblasts themselves. These results suggest that epithelial
      mesenchymal interaction is likely involved in growth and differentiation of
      epithelial cells in vivo in a soluble factor(s)-mediated manner. As well as the
      epithelial cells, the fibroblasts also formed a multilayer during the last 10 d
      of co-culturing. This indicates that in vitro reconstitution of tracheal
      epithelia is achieved without addition of any exogenous growth or differentiation
      factors. The reconstitution system is shown to be useful for investigating the
      cellular and molecular interaction of epithelial and mesenchymal cells. Possible
      applications of the culture system and possible factors involved in growth and
      differentiation of epithelial cells are discussed.

PMID- 9922224
TI  - Expression and regulation of protein inhibitor of neuronal nitric oxide synthase
      in ventilatory muscles.
AB  - In skeletal muscle fibers, nitric oxide (NO) is synthesized by neuronal NO
      synthase (nNOS) and regulates excitation-contraction coupling, glucose uptake,
      and mitochondrial respiration. Recently, a novel 89-amino acid protein,
      designated protein inhibitor of nNOS (PIN), has been shown to interact with and
      specifically inhibit nNOS activity. In this study, we investigated the
      distribution, localization, and regulation of PIN expression in ventilatory and
      limb muscles of various species. Amplified PIN cDNA from the rat diaphragm
      revealed an open reading frame identical to that of human PIN. Among muscles of
      adult rats, PIN mRNA was strongly expressed in muscles rich in type I fibers,
      whereas much weaker expression was evident in muscles rich in type II fibers. By
      comparison, PIN protein expression was not related to fiber-type distribution.
      Similarly, PIN protein was equally expressed among rat, mouse, and human
      diaphragms. Both PIN mRNA and PIN protein were expressed at much higher levels in
      the embryonic rat diaphragm than in adult muscle. Immunohistochemistry revealed
      that PIN protein was localized in close proximity to the sarcolemma and nuclei.
      PIN protein was also abundant in muscle spindles and axons of nerves supplying
      skeletal muscle fibers. We conclude that PIN is expressed in various skeletal
      muscle fibers and that its expression is regulated during muscle development. The
      localization of PIN in muscle regions containing abundant nNOS protein suggests
      that it plays a role in the regulation of NO synthesis in skeletal muscle fibers.

PMID- 9922225
TI  - Isolation of a gene product expressed by a subpopulation of human lung
      fibroblasts by differential display.
AB  - Fibroblasts are the major cell type responsible for synthesizing matrix
      constituents in lung and other connective tissues. Evidence indicates that
      fibroblasts are heterogeneous, and that subpopulations with some distinct
      properties are clonally selected and expanded in fibrotic diseases. However, few
      distinct markers capable of demonstrating the presence of fibroblast
      subpopulations in tissues have been isolated so far. With the objective of
      identifying proteins that could detect fibroblast subpopulations, we compared the
      messenger RNA (mRNA) expression of two cultured human lung fibroblast
      subpopulations by differential display. Total RNA was obtained, complementary DNA
      (cDNA) was synthesized, and the polymerase chain reaction (PCR) products obtained
      with several primer pairs were compared. One 724-bp product, which was strongly
      expressed by one human lung fibroblast subpopulation, was identified and cloned.
      This product was poorly expressed by the other lung fibroblast subpopulation. The
      mRNA for the gene encoding this product was not detectable in human smooth-muscle
      cells, endothelial cells, or epithelial cells, although it was present in dermal
      fibroblasts. The mRNA was detected in normal and fibrotic human lungs. Search of
      the National Center for Biotechnology (NCBI) GenBank DNA database with the
      sequence obtained from this clone revealed no significant matches. However, a
      search of the NCBI database of expressed sequence tags (dBEST) revealed five
      different human expressed sequence tag (EST) clones corresponding to the LR8 cDNA
      sequence. Six additional mouse and one pig EST clones were identified that showed
      significant similarity to the human fibroblast cDNA. Composites of the entire
      coding sequences for the human fibroblast gene product and the mouse homologue
      were assembled from the respective overlapping EST sequences. The open reading
      frame identified for each composite sequence predicted protein products of 270
      and 263 amino acids for the human and mouse sequences, respectively, which were
      52% identical, with three gaps. At the amino acid level, no significant sequence
      similarity was detected with any other sequences in exhaustive searches of the
      NCBI DNA and protein databases or the Blocks databases. A PCR product with
      predicted length and sequence was obtained by using a sense primer upstream to
      LR8 and an antisense primer within LR8. Our results indicate that this
      differentially displayed product represents a previously undescribed protein that
      could be useful for distinguishing fibroblasts, and possibly fibroblast
      subpopulations, from other cell types in lungs and other tissues.

PMID- 9922226
TI  - Peptide growth factors regulate insulin-like growth factor binding protein
      production by fetal rat lung fibroblasts.
AB  - Insulin-like growth factor (IGF) binding proteins (IGFBPs) are expressed in fetal
      lung and may provide important post-translational regulation of IGF-induced
      mitogenesis during lung organogenesis. Because of the observation that growth
      factors can control cell growth through regulation of IGFBPs, we examined IGFBP
      production by fetal lung fibroblasts following stimulation by peptide growth
      factors important for fetal lung growth and development. Fetal lung fibroblasts
      were cultured in serum-free medium supplemented with various growth factors for
      up to 48 h, and IGFBPs in conditioned medium (CM) were analyzed by ligand blot
      and immunoblot techniques. Accumulation of CM IGFBP-3 was increased and IGFBP-2
      decreased by incubation with either keratinocyte growth factor (KGF) or epidermal
      growth factor (EGF). The effect of these factors on IGFBP-3 accumulation
      increased with time but the effects of KGF on CM IGFBP-2 decreased over 48 h of
      incubation. CM IGFBP-4 was increased by 24 and 48 h incubation with basic
      fibroblast growth factor (bFGF; 2.1- and 2.7-fold increases at 24 and 48 h,
      respectively) and platelet-derived growth factor-BB (PDGF-BB; 4.2- and 14.9-fold
      increases at 24 and 48 h, respectively), and 48 h incubation with EGF (6.3-fold
      increase). In 48-h coincubation experiments, EGF in combination with PDGF-BB or
      with bFGF, and bFGF in combination with PDGF-BB, resulted in IGFBP-4
      accumulations twice that expected from a summation of the effects of either
      growth factor alone (IGFBP-4 increased 9.8-, 4.0-, and 1.8-fold by PDGF-BB, EGF,
      and bFGF, respectively; and 27.1-, 37.3-, and 13.0-fold by PDGF-BB plus EGF, PDGF
      BB plus bFGF, and EGF plus bFGF, respectively). These results suggest synergistic
      effects of these growth factors on IGFBP-4 accumulation in fetal lung fibroblast
      CM. Because IGFBPs are known to regulate DNA synthesis, we speculate that peptide
      growth factors may alter cell proliferation in fetal lung, in part through their
      effect on IGFBPs.

PMID- 9922227
TI  - Histochemical demonstration of neuronal nitric oxide synthase during development
      of mouse respiratory tract.
AB  - Several studies, including histochemical ones, have indicated that nitric oxide
      (NO) of endothelial origin may be related to the pulmonary vasodilation that
      occurs at birth. Since no histologic studies have been done of the possible
      parallel perinatal increase in production of neuronal NO synthase (nNOS) by
      pulmonary nerve plexuses, we investigated the distribution of nNOS in fetal,
      neonatal, and adult mouse lung. Lungs from mice aged 13 d gestation to 6 d after
      birth and lungs of adults were studied through histochemistry for nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and
      immunocytochemistry. Both techniques gave almost similar results in relation to
      time of appearance, distribution, and frequency of neural structures positive for
      NADPH-d and NOS. NADPH-d staining was also applied to whole mounts of developing
      and adult tracheae. Staining was found from gestational days 13 to 15 onward in a
      small portion of the neuronal population. In all stages studied, NADPH-d/NOS
      staining was found in neuron cell bodies in the hilar region and bronchiolar
      wall, as well as in neuronal processes. Labeled terminal nerve fibers with
      varicosities were more frequent in pulmonary blood vessels than in airways. In
      tracheae, similar NADPH-d/NOS-positive nerve plexuses were found. The presence of
      nNOS in fetal and neonatal mouse respiratory tract suggests that neurally derived
      NO must play a role in developing lung physiology. However, because no perinatal
      increase in the number or intensity of staining of nNOS-positive nerve structures
      was seen, no apparent relation between neural NO and vasodilation can be
      established at birth.

PMID- 9922228
TI  - Forskolin inhibits cyclin D1 expression in cultured airway smooth-muscle cells.
AB  - Accumulation of intracellular cyclic adenosine monophosphate (cAMP) has been
      shown to inhibit the growth of cultured airway smooth-muscle cells, but the
      precise mechanism underlying the antimitogenic action of cAMP in these cells is
      unknown. We examined the effects of forskolin, an activator of adenylate cyclase,
      on DNA synthesis, cyclin D1 expression, and cAMP response element-binding protein
      (CREB) phosphorylation and DNA binding in bovine tracheal myocytes. DNA synthesis
      was assessed by measurement of [3H]thymidine incorporation. Cyclin D1 protein
      abundance and CREB phosphorylation were assessed by immunoblotting. Cyclin D1
      promoter transcriptional activation was determined by measurement of luciferase
      activity in cells transiently cotransfected with complementary DNAs encoding the
      full-length cyclin D1 promoter subcloned into a luciferase reporter and beta
      galactosidase (to normalize for transfection efficiency). The binding of nuclear
      proteins to the cyclin D1 promoter cAMP response element (CRE) was determined by
      electrophoretic mobility shift assay. We found that forskolin attenuated platelet
      derived growth factor-induced DNA synthesis in a concentration-dependent manner.
      In addition, forskolin pretreatment decreased both cyclin D1 promoter activity
      and protein levels. Forskolin treatment induced the phosphorylation of CREB and
      increased the binding of nuclear protein to the cyclin D1 promoter CRE. Finally,
      addition of an antibody against CREB1 induced supershift of at least one protein
      DNA complex. Together, these data suggest that cAMP suppresses cyclin D1 gene
      expression via phosphorylation and transactivation of CREB. Further studies are
      needed to determine whether this is the primary mechanism of cAMP-induced growth
      inhibition, or whether additional pathways are also involved.

PMID- 9922229
TI  - Growth in studying the cessation of growth.

PMID- 9922230
TI  - The bZip transcription factor Cap1p is involved in multidrug resistance and
      oxidative stress response in Candida albicans.
AB  - Candida albicans is an opportunistic pathogenic yeast which frequently develops
      resistance to the antifungal agent fluconazole (FCZ) in patients undergoing long
      term therapy. FCZ-resistant strains often display a reduced intracellular FCZ
      accumulation which correlates with the overexpression of the ATP-binding cassette
      transporters CDR1 and CDR2 or the major facilitator (MF) MDR1. We have recently
      cloned a C. albicans gene, named CAP1, which codes for a bZip transcription
      factor of the AP-1 family homologous to the Yap1 protein involved in multidrug
      resistance and response to oxidative stress in Saccharomyces cerevisiae. CAP1 was
      found to confer FCZ resistance in S. cerevisiae by transcriptionally activating
      FLR1, a gene coding for an MF homologous to the C. albicans MDR1 gene product (A.
      M. Alarco, I. Balan, D. Talibi, N. Mainville, and M. Raymond, J. Biol. Chem.
      272:19304-19313, 1997). To study the role of CAP1 in C. albicans, we constructed
      a CAI4-derived mutant strain carrying a homozygous deletion of the CAP1 gene
      (CJD21). We found that deletion of CAP1 did not affect the susceptibility of
      CJD21 cells to FCZ, cerulenin, brefeldin A, and diamide but caused
      hypersensitivity to cadmium, 4-nitroquinoline N-oxide, 1,10-phenanthroline, and
      hydrogen peroxide, an effect which was reverted by reintroduction of the CAP1
      gene in these cells. Introduction of a hyperactive truncated allele of CAP1 (CAP1
      TR) in CJD21 resulted in resistance of the cells to all of the above compounds
      except hydrogen peroxide. The hyperresistant phenotype displayed by the CJD21
      CAP1-TR transformants was found to correlate with the overexpression of a number
      of potential CAP1 transcriptional targets such as MDR1, CaYCF1, CaGLR1, and
      CaTRR1. Taken together, our results demonstrate that CAP1 is involved in
      multidrug resistance and oxidative stress response in C. albicans. Finally,
      disruption of CAP1 in strain FR2, selected in vitro for FCZ resistance and
      constitutively overexpressing MDR1, did not suppress but rather increased the
      levels of MDR1 expression, demonstrating that CAP1 acts as a negative
      transcriptional regulator of the MDR1 gene in FR2 and is not responsible for MDR1
      overexpression in this strain.

PMID- 9922231
TI  - The HPr(Ser) kinase of Streptococcus salivarius: purification, properties, and
      cloning of the hprK gene.
AB  - In gram-positive bacteria, HPr, a protein of the phosphoenolpyruvate:sugar
      phosphotransferase system, is phosphorylated on a serine residue at position 46
      by an ATP-dependent protein kinase. The HPr(Ser) kinase of Streptococcus
      salivarius ATCC 25975 was purified, and the encoding gene (hprK) was cloned by
      using a nucleotide probe designed from the N-terminal amino acid sequence. The
      predicted amino acid sequence of the S. salivarius enzyme showed 45% identity
      with the Bacillus subtilis enzyme, the conserved residues being located mainly in
      the C-terminal half of the protein. The predicted hprK gene product has a
      molecular mass of 34,440 Da and a pI of 5.6. These values agree well with those
      found experimentally by polyacrylamide gel electrophoresis in the presence of
      sodium dodecyl sulfate, molecular sieve chromatography in the presence of
      guanidine hydrochloride, and chromatofocusing using the purified protein. The
      native protein migrates on a Superdex 200 HR column as a 330,000-Da protein,
      suggesting that the HPr(Ser) kinase is a decamer. The enzyme requires Mg2+ for
      activity and functions optimally at pH 7.5. Unlike the enzyme from other gram
      positive bacteria, the HPr(Ser) kinase from S. salivarius is not stimulated by
      FDP or other glycolytic intermediates. The enzyme is inhibited by inorganic
      phosphate, and its Kms for HPr and ATP are 31 microM and 1 mM, respectively.

PMID- 9922232
TI  - Purification and properties of NADH-dependent 5, 10-methylenetetrahydrofolate
      reductase (MetF) from Escherichia coli.
AB  - A K-12 strain of Escherichia coli that overproduces methylenetetrahydrofolate
      reductase (MetF) has been constructed, and the enzyme has been purified to
      apparent homogeneity. A plasmid specifying MetF with six histidine residues added
      to the C terminus has been used to purify histidine-tagged MetF to homogeneity in
      a single step by affinity chromatography on nickel-agarose, yielding a
      preparation with specific activity comparable to that of the unmodified enzyme.
      The native protein comprises four identical 33-kDa subunits, each of which
      contains a molecule of noncovalently bound flavin adenine dinucleotide (FAD). No
      additional cofactors or metals have been detected. The purified enzyme catalyzes
      the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, using NADH
      as the reductant. Kinetic parameters have been determined at 15 degreesC and pH
      7.2 in a stopped-flow spectrophotometer; the Km for NADH is 13 microM, the Km for
      CH2-H4folate is 0.8 microM, and the turnover number under Vmax conditions
      estimated for the reaction is 1,800 mol of NADH oxidized min-1 (mol of enzyme
      bound FAD)-1. NADPH also serves as a reductant, but exhibits a much higher Km.
      MetF also catalyzes the oxidation of methyltetrahydrofolate to
      methylenetetrahydrofolate in the presence of menadione, which serves as an
      electron acceptor. The properties of MetF from E. coli differ from those of the
      ferredoxin-dependent methylenetetrahydrofolate reductase isolated from the
      homoacetogen Clostridium formicoaceticum and more closely resemble those of the
      NADH-dependent enzyme from Peptostreptococcus productus and the NADPH-dependent
      enzymes from eukaryotes.

PMID- 9922233
TI  - The merG gene product is involved in phenylmercury resistance in Pseudomonas
      strain K-62.
AB  - The physiological function of a new gene, hereby designated merG, located between
      merA and merB on the broad-spectrum mer operon of Pseudomonas strain K-62 plasmid
      pMR26 was investigated. The 654-bp merG gene encodes a protein with a canonical
      leader sequence at its N terminus. The processing of the signal peptide of this
      protein was dose-dependently inhibited by sodium azide, a potent inhibitor of
      protein export. These results suggest that the mature MerG protein (ca. 20 kDa)
      may be located in the periplasm. Deletion of the merG gene from the broad
      spectrum mer operon of pMR26 had no effect on the inorganic mercury resistance
      phenotype, but rendered the bacterium more sensitive to phenylmercury than its
      isogenic wild-type strain. Escherichia coli cells bearing pMU29, which carries a
      deletion of the merG gene, took up significantly more phenylmercury than the
      bacteria with the intact plasmid pMRA17. When the merG gene in a compatible
      plasmid was transformed into the E. coli strain carrying pMU29, the high uptake
      of and high sensitivity to phenylmercury were almost completely restored to their
      original levels. These results demonstrate that the merG gene is involved in
      phenylmercury resistance, presumably by reducing in-cell permeability to
      phenylmercury.

PMID- 9922234
TI  - Neisseria gonorrhoeae PilA is an FtsY homolog.
AB  - The pilA gene of Neisseria gonorrhoeae was initially identified in a screen for
      transcriptional regulators of pilE, the expression locus for pilin, the major
      structural component of gonococcal pili. The predicted protein sequence for PilA
      has significant homology to two GTPases of the mammalian signal recognition
      particle (SRP), SRP54 and SRalpha. Homologs of SRP54 and SRalpha were
      subsequently identified in bacteria (Ffh and FtsY, respectively) and appear to
      form an SRP-like apparatus in prokaryotes. Of the two proteins, PilA is the most
      similar to FtsY (47% identical and 67% similar at the amino acid level). Like
      FtsY, PilA is essential for viability and hydrolyzes GTP. The similarities
      between PilA and the bacterial FtsY led us to ask whether PilA might function as
      the gonococcal FtsY. In this work, we show that overproduction of PilA in
      Escherichia coli leads to an accumulation of pre-beta-lactamase, similar to
      previous observations with other bacterial SRP components. Low-level expression
      of pilA in an ftsY conditional mutant can complement the ftsY mutation and
      restore normal growth to this strain under nonpermissive conditions. In addition,
      purified PilA can replace FtsY in an in vitro translocation assay using purified
      E. coli SRP components. A PilA mutant that is severely affected in its GTPase
      activity cannot replace FtsY in vivo or in vitro. However, overexpression of the
      GTPase mutant leads to the accumulation of pre-beta-lactamase, suggesting that
      the mutant protein may interact with the SRP apparatus to affect protein
      maturation. Taken together, these results show that the gonococcal PilA is an
      FtsY homolog and that the GTPase activity is necessary for its function.

PMID- 9922235
TI  - Membrane-mimicking entities induce structuring of the two-peptide bacteriocins
      plantaricin E/F and plantaricin J/K.
AB  - Lactobacillus plantarum C11 produces plantaricin E/F (PlnE/F) and plantaricin J/K
      (PlnJ/K), two bacteriocins whose activity depends on the complementary action of
      two peptides (PlnE and PlnF; PlnJ and PlnK). Three of the individual Pln peptides
      possess some antimicrobial activity, but the highest bacteriocin activity is
      obtained by combining complementary peptides in about a one-to-one ratio.
      Circular dichroism was used to study the structure of the Pln peptides under
      various conditions. All four peptides were unstructured under aqueous conditions
      but adopted a partly alpha-helical structure in the presence of trifluoroethanol,
      micelles of dodecylphosphocholine, and negatively charged dioleoylphosphoglycerol
      (DOPG) liposomes. Far less structure was induced by zwitterionic
      dioleoylglycerophosphocholine liposomes, indicating that a net negative charge on
      the phospholipid bilayer is important for a structure-inducing interaction
      between (positively charged) Pln peptides and a membrane. The structuring of
      complementary peptides was considerably enhanced when both (PlnE and PlnF or PlnJ
      and PlnK) were added simultaneously to DOPG liposomes. Such additional
      structuring was not observed in experiments with trifluoroethanol or
      dodecylphosphocholine, indicating that the apparent structure-inducing
      interaction between complementary Pln peptides requires the presence of a
      phospholipid bilayer. The amino acid sequences of the Pln peptides are such that
      the alpha-helical structures adopted upon interaction with the membrane and each
      other are amphiphilic in nature, thus enabling membrane interactions.

PMID- 9922236
TI  - Quorum sensing in Burkholderia cepacia: identification of the LuxRI homologs
      CepRI.
AB  - Burkholderia cepacia has emerged as an important pathogen in patients with cystic
      fibrosis. Many gram-negative pathogens regulate the production of extracellular
      virulence factors by a cell density-dependent mechanism termed quorum sensing,
      which involves production of diffusible N-acylated homoserine lactone signal
      molecules, called autoinducers. Transposon insertion mutants of B. cepacia K56-2
      which hyperproduced siderophores on chrome azurol S agar were identified. One
      mutant, K56-R2, contained an insertion in a luxR homolog that was designated
      cepR. The flanking DNA region was used to clone the wild-type copy of cepR.
      Sequence analysis revealed the presence of cepI, a luxI homolog, located 727 bp
      upstream and divergently transcribed from cepR. A lux box-like sequence was
      identified upstream of cepI. CepR was 36% identical to Pseudomonas aeruginosa
      RhlR and 67% identical to SolR of Ralstonia solanacearum. CepI was 38% identical
      to RhlI and 64% identical to SolI. K56-R2 demonstrated a 67% increase in the
      production of the siderophore ornibactin, was protease negative on dialyzed brain
      heart infusion milk agar, and produced 45% less lipase activity in comparison to
      the parental strain. Complementation of a cepR mutation restored parental levels
      of ornibactin and protease but not lipase. An N-acylhomoserine lactone was
      purified from culture fluids and identified as N-octanoylhomoserine lactone. K56
      I2, a cepI mutant, was created and shown not to produce N-octanoylhomoserine
      lactone. K56-I2 hyperproduced ornibactin and did not produce protease. These data
      suggest both a positive and negative role for cepIR in the regulation of
      extracellular virulence factor production by B. cepacia.

PMID- 9922237
TI  - Structure of the ring cleavage product of 1-hydroxy-2-naphthoate, an intermediate
      of the phenanthrene-degradative pathway of Nocardioides sp. strain KP7.
AB  - 1-Hydroxy-2-naphthoate (compound I) is a metabolite of the phenanthrene
      degradative pathway in Nocardioides sp. strain KP7. This singly hydroxylated
      aromatic compound is cleaved by 1-hydroxy-2-naphthoate dioxygenase. In this
      study, the structure of the ring cleavage product generated by the action of
      homogeneous 1-hydroxy-2-naphthoate dioxygenase was determined upon separation by
      high-performance liquid chromatography at pH 2.5 by using nuclear magnetic
      resonance (NMR) and mass spectroscopic techniques. The ring cleavage product at
      this pH existed in equilibrium between two forms, 2-oxo-3-(3-oxo-1,3-dihydro-1
      isobenzofuranyl)propanoate (compound III) and 2,2-dihydroxy-3-(3-oxo-1, 3-dihydro
      1-isobenzofuranyl)propanoate (compound IV). After the pH of the solution was
      raised to 7.5, the structure of the major species became (E)-4-(2
      carboxylatophenyl)-2-oxo-3-butenoate (compound II; common name, trans-2'
      carboxybenzalpyruvate), which was in equilibrium with compound III. Direct
      monitoring of the enzymatic formation of the ring cleavage product by 1H-NMR in a
      deuterated potassium phosphate buffer (pH 7.5) detected only compound II as a
      product, and the proton on carbon 3 of compound II was not exchanged with
      deuterium. Thus, compound II is likely to be the first stable product of
      dioxygenation of 1-hydroxy-2-naphthoate.

PMID- 9922238
TI  - Molecular characterization of the Lactococcus lactis ptsHI operon and analysis of
      the regulatory role of HPr.
AB  - The Lactococcus lactis ptsH and ptsI genes, encoding the general proteins of the
      phosphoenolpyruvate-dependent phosphotransferase system, HPr and enzyme I,
      respectively, were cloned, and the regulatory role of HPr was studied by
      mutational analysis of its gene. A promoter sequence was identified upstream of
      the ptsHI operon, and the transcription start site was mapped by primer
      extension. The results of Northern analyses showed the presence of two glucose
      inducible transcripts, one of 0.3 kb containing ptsH and a second of 2.0 kb
      containing both ptsH and ptsI. Disruption of the ptsH and ptsI genes in strain
      NZ9800 resulted in a reduced growth rate at the expense of glucose, but no growth
      at the expense of sucrose and fructose, confirming the dominant role of the
      phosphotransferase system in the uptake of these sugars in L. lactis.
      Complementation of the ptsH and ptsI mutants with the intact genes under the
      control of a regulated promoter resulted in the restoration of the wild-type
      phenotype. The role of HPr(Ser-P) in the recently established CcpA-mediated
      control of galactose metabolism as well as glycolysis was analyzed by producing
      an HPr mutant carrying an aspartic acid on residue 46 which mimicks a
      phosphorylated serine. The results of these experiments demonstrated the role of
      HPr(Ser-P) as corepressor in the catabolite repression of the gal operon.
      Furthermore, we show for the first time that HPr(Ser-P) functions as a
      coactivator in the CcpA-mediated catabolite activation of the pyruvate kinase and
      L-lactate dehydrogenase genes.

PMID- 9922239
TI  - Assembly of the K40 antigen in Escherichia coli: identification of a novel enzyme
      responsible for addition of L-serine residues to the glycan backbone and its
      requirement for K40 polymerization.
AB  - Escherichia coli O8:K40 coexpresses two distinct lipopolysaccharide (LPS)
      structures on its surface. The O8 polysaccharide is a mannose homopolymer with a
      trisaccharide repeat unit and is synthesized by an ABC-2 transport-dependent
      pathway. The K40LPS backbone structure is composed of a trisaccharide repeating
      unit of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) and has an
      uncommon substitution, an L-serine moiety attached to glucuronic acid. The gene
      cluster responsible for synthesis of the K40 polysaccharide has previously been
      cloned and sequenced and was found to contain six open reading frames (ORFs) (P.
      A. Amor and C. Whitfield, Mol. Microbiol. 26:145-161, 1997). Here, we demonstrate
      that insertional inactivation of orf1 results in the accumulation of a semirough
      (SR)-K40LPS form which retains reactivity with specific polyclonal serum in
      Western immunoblots. Structural and compositional analysis of the SR-K40LPS
      reveals that it comprises a single K40 repeat unit attached to lipid A core. The
      lack of polymerization of the K40 polysaccharide indicates that orf1 encodes the
      K40 polymerase (Wzy) and that assembly of the K40 polysaccharide occurs via a Wzy
      dependent pathway (in contrast to that of the O8 polysaccharide). Inactivation of
      orf3 also results in the accumulation of an SR-LPS form which fails to react with
      specific polyclonal K40 serum in Western immunoblots. Methylation linkage
      analysis and fast atom bombardment-mass spectrometry of this SR-LPS reveals that
      the biological repeat unit of the K40 polysaccharide is GlcNAc-GlcA-GlcNAc.
      Additionally, this structure lacks the L-serine substitution of GlcA. These
      results show that (i) orf3 encodes the enzyme responsible for the addition of the
      L-serine residue to the K40 backbone and (ii) substitution of individual K40
      repeats with L-serine is essential for their recognition and polymerization into
      the K40 polysaccharide by Wzy.

PMID- 9922240
TI  - A four-dimensional view of assembly of a morphogenetic protein during sporulation
      in Bacillus subtilis.
AB  - We report the use of a fusion to the green fluorescent protein to visualize the
      assembly of the morphogenetic protein SpoIVA around the developing forespore
      during the process of sporulation in the bacterium Bacillus subtilis. Using a
      deconvolution algorithm to process digitally-collected optical sections, we show
      that SpoIVA, which is synthesized in the mother cell chamber of the sporangium,
      assembled into a spherical shell around the outer surface of the forespore. Time
      lapse fluorescence microscopy showed that this assembly process commenced at the
      time of polar division and seemed to continue after engulfment of the forespore
      was complete. SpoIVA remained present throughout the late stages of morphogenesis
      and was present as a component of the fully mature spore. Evidence indicates that
      assembly of SpoIVA depended on the extreme C-terminal region of the protein and
      an additional region that directly or indirectly facilitated interaction among
      SpoIVA molecules. The N- and C-terminal regions of SpoIVA, including the extreme
      C terminus, are highly similar to the corresponding regions of the homologous
      protein from the distantly related endospore-forming bacterium Clostridium
      acetobutylicum, attesting to their importance in the function of the protein.
      Finally, we show that proper localization of SpoIVA required the expression of
      one or more genes which, like spoIVA, are under the control of the mother cell
      transcription factor sigmaE. One such gene was spoVM, whose product was required
      for efficient targeting of SpoIVA to the outer surface of the forespore.

PMID- 9922241
TI  - Excretion of endogenous cadaverine leads to a decrease in porin-mediated outer
      membrane permeability.
AB  - The permeability of the outer membrane of Escherichia coli to hydrophilic
      compounds is controlled by porin channels. Electrophysiological experiments
      showed that polyamines inhibit ionic flux through cationic porins when applied to
      either side of the membrane. Externally added polyamines, such as cadaverine,
      decrease porin-mediated fluxes of beta-lactam antibiotics in live cells. Here we
      tested the effects of endogenously expressed cadaverine on the rate of permeation
      of cephaloridine through porins, by manipulating in a pH-independent way the
      expression of the cadBA operon, which encodes proteins involved in the
      decarboxylation of lysine to cadaverine and in cadaverine excretion. We report
      that increased levels of excreted cadaverine correlate with a decreased outer
      membrane permeability to cephaloridine, without any change in porin expression.
      Cadaverine appears to promote a sustained inhibition of porins, since the effect
      remains even after removal of the exogenously added or excreted polyamine. The
      cadaverine-induced inhibition is sufficient to provide cells with some resistance
      to ampicillin but not to hydrophobic antibiotics. Finally, the mere expression of
      cadC, in the absence of cadaverine production, leads to a reduction in the
      amounts of OmpF and OmpC proteins, which suggests a novel mechanism for the
      environmental control of porin expression. The results presented here support the
      notion that polyamines can act as endogenous modulators of outer membrane
      permeability, possibly as part of an adaptive response to acidic conditions.

PMID- 9922242
TI  - Coordinate intracellular expression of Salmonella genes induced during infection.
AB  - Salmonella typhimurium in vivo-induced (ivi) genes were grouped by their
      coordinate behavior in response to a wide variety of environmental and genetic
      signals, including pH, Mg2+, Fe2+, and PhoPQ. All of the seven ivi fusions that
      are induced by both low pH and low Mg2+ (e.g., iviVI-A) are activated by the
      PhoPQ regulatory system. Iron-responsive ivi fusions include those induced under
      iron limitation (e.g., entF) as well as one induced by iron excess but only in
      the absence of PhoP (pdu). Intracellular expression studies showed that each of
      the pH- and Mg2+-responsive fusions is induced upon entry into and growth within
      three distinct mammalian cell lines: RAW 264.7 murine macrophages and two
      cultured human epithelial cell lines: HEp-2 and Henle-407. Each ivi fusion has a
      characteristic level of induction consistent within all three cell types,
      suggesting that this class of coordinately expressed ivi genes responds to
      general intracellular signals that are present both in initial and in progressive
      stages of infection and may reflect their responses to similar vacuolar
      microenvironments in these cell types. Investigation of ivi expression patterns
      reveals not only the inherent versatility of pathogens to express a given gene(s)
      at various host sites but also the ability to modify their expression within the
      context of different animal hosts, tissues, cell types, or subcellular
      compartments.

PMID- 9922243
TI  - The presence of glutamate dehydrogenase is a selective advantage for the
      Cyanobacterium synechocystis sp. strain PCC 6803 under nonexponential growth
      conditions.
AB  - The unicellular cyanobacterium Synechocystis sp. strain PCC 6803 has two putative
      pathways for ammonium assimilation: the glutamine synthetase-glutamate synthase
      cycle, which is the main one and is finely regulated by the nitrogen source; and
      a high NADP-dependent glutamate dehydrogenase activity (NADP-GDH) whose
      contribution to glutamate synthesis is uncertain. To investigate the role of the
      latter, we used two engineered mutants, one lacking and another overproducing
      NADP-GDH. No major disturbances in the regulation of nitrogen-assimilating
      enzymes or in amino acids pools were detected in the null mutant, but phycobiline
      content, a sensitive indicator of the nutritional state of cyanobacterial cells,
      was significantly reduced, indicating that NADP-GDH plays an auxiliary role in
      ammonium assimilation. This effect was already prominent in the initial phase of
      growth, although differences in growth rate between the wild type and the mutants
      were observed at this stage only at low light intensities. However, the null
      mutant was unable to sustain growth at the late stage of the culture at the point
      when the wild type showed the maximum NADP-GDH activity, and died faster in
      ammonium-containing medium. Overexpression of NADP-GDH improved culture
      proliferation under moderate ammonium concentrations. Competition experiments
      between the wild type and the null mutant confirmed that the presence of NADP-GDH
      confers a selective advantage to Synechocystis sp. strain PCC 6803 in late stages
      of growth.

PMID- 9922244
TI  - Thermoregulated expression and characterization of an NAD(P)H-dependent 2
      cyclohexen-1-one reductase in the plant pathogenic bacterium Pseudomonas syringae
      pv. glycinea.
AB  - The phytopathogenic bacterium Pseudomonas syringae pv. glycinea PG4180.N9 causes
      bacterial blight of soybeans and preferably infects its host plant during periods
      of cold, humid weather conditions. To identify proteins differentially expressed
      at low temperatures, total cellular protein fractions derived from PG4180.N9
      grown at 18 and 28 degreesC were separated by two-dimensional gel
      electrophoresis. Of several proteins which appeared to be preferentially present
      at 18 degreesC, a 40-kDa protein with an isoelectric point of approximately 5
      revealed significant N-terminal sequence homology to morphinone reductase (MR) of
      Pseudomonas putida M10. The respective P. syringae gene was isolated from a
      genomic cosmid library of PG4180, and its nucleotide sequence was determined. It
      was designated ncr for NAD(P)H-dependent 2-cyclohexen-1-one reductase. Comparison
      of the 1,083-bp open reading frame with database entries revealed 48% identity
      and 52% similarity to the MR-encoding morB gene of P. putida M10. The ncr gene
      was overexpressed in Escherichia coli, and its gene product was used to generate
      polyclonal antisera. Purified recombinant Ncr protein was enzymatically
      characterized with NAD(P)H and various morphinone analogs as substrates. So far,
      only 2-cyclohexen-1-one and 3-penten-2-one were found to be substrates for Ncr.
      By high-pressure liquid chromatography analysis, flavin mononucleotide could be
      identified as the noncovalently bound prosthetic group of this enzyme. The
      distribution of the ncr gene in different Pseudomonas species and various strains
      of P. syringae was analyzed by PCR and Southern blot hybridization. The results
      indicated that the ncr gene is widespread among P. syringae pv. glycinea strains
      but not in other pathovars of P. syringae or in any of the other Pseudomonas
      strains tested.

PMID- 9922245
TI  - Analysis of FtsZ assembly by light scattering and determination of the role of
      divalent metal cations.
AB  - FtsZ is an ancestral homologue of tubulin that polymerizes in a GTP-dependent
      manner. In this study, we used 90 degrees angle light scattering to investigate
      FtsZ polymerization. The critical concentration for polymerization obtained by
      this method is similar to that obtained by centrifugation, confirming that the
      light scattering is proportional to polymer mass. Furthermore, the dynamics of
      FtsZ polymerization could be readily monitored by light scattering.
      Polymerization was very rapid, reaching steady state within 30 s. The length of
      the steady-state phase was proportional to the GTP concentration and was followed
      by a rapid decrease in light scattering. This decrease indicated net
      depolymerization that always occurred as the GTP in the reaction was consumed.
      FtsZ polymerization was observed over the pH range 6.5 to 7.9. Importantly, Mg2+
      was not required for polymerization although it was required for the dynamic
      behavior of the polymers. It was reported that 7 to 25 mM Ca2+ mediated dynamic
      assembly of FtsZ (X. -C. Yu and W. Margolin, EMBO J. 16:5455-5463, 1997).
      However, we found that Ca2+ was not required for FtsZ assembly and that this
      concentration of Ca2+ reduced the dynamic behavior of FtsZ assembly.

PMID- 9922246
TI  - Immunochemical analysis of UMP kinase from Escherichia coli.
AB  - Mono- and polyclonal antibodies directed against UMP kinase from Escherichia coli
      were tested with the intact protein or with fragments obtained by deletion
      mutagenesis. As detected in enzyme-linked immunosorbent assay tests, the carboxy
      terminal quarter of UMP kinase is immunodominant. Polyclonal antibodies inhibited
      the enzyme activity with partial or total loss of allosteric effects exerted by
      UTP and GTP, respectively. These data indicate that the UTP and GTP binding sites
      in UMP kinase are only partially overlapping. One monoclonal antibody (44-2)
      recognized a linear epitope in UMP kinase between residues 171 and 180. A single
      substitution (D174N) in this segment of the enzyme abolished its interaction with
      the monoclonal antibody (44-2). Polyclonal antisera were used to identify UMP
      kinase in the bacterial proteome. The enzyme appears as a single spot on two
      dimensional electrophoresis at a pI of 7.24 and an apparent molecular mass of 26
      kDa. Immunogold labeling of UMP kinase in whole E. coli cells shows a
      localization of the protein near the bacterial membranes. Because the protein
      does not contain sequences usually required for compartmentalization, the
      aggregation properties of UMP kinase observed in vitro might play a role in this
      phenomenon. The specific localization of UMP kinase might also be related to its
      putative role in cell division.

PMID- 9922248
TI  - Poly-3-hydroxybutyrate degradation in Rhizobium (Sinorhizobium) meliloti:
      isolation and characterization of a gene encoding 3-hydroxybutyrate
      dehydrogenase.
AB  - We have cloned and sequenced the 3-hydroxybutyrate dehydrogenase-encoding gene
      (bdhA) from Rhizobium (Sinorhizobium) meliloti. The gene has an open reading
      frame of 777 bp that encodes a polypeptide of 258 amino acid residues (molecular
      weight 27,177, pI 6.07). The R. meliloti Bdh protein exhibits features common to
      members of the short-chain alcohol dehydrogenase superfamily. bdhA is the first
      gene transcribed in an operon that also includes xdhA, encoding xanthine
      oxidase/dehydrogenase. Transcriptional start site analysis by primer extension
      identified two transcription starts. S1, a minor start site, was located 46 to 47
      nucleotides upstream of the predicted ATG start codon, while S2, the major start
      site, was mapped 148 nucleotides from the start codon. Analysis of the sequence
      immediately upstream of either S1 or S2 failed to reveal the presence of any
      known consensus promoter sequences. Although a sigma54 consensus sequence was
      identified in the region between S1 and S2, a corresponding transcript was not
      detected, and a rpoN mutant of R. meliloti was able to utilize 3-hydroxybutyrate
      as a sole carbon source. The R. meliloti bdhA gene is able to confer upon
      Escherichia coli the ability to utilize 3-hydroxybutyrate as a sole carbon
      source. An R. meliloti bdhA mutant accumulates poly-3-hydroxybutyrate to the same
      extent as the wild type and shows no symbiotic defects. Studies with a strain
      carrying a lacZ transcriptional fusion to bdhA demonstrated that gene expression
      is growth phase associated.

PMID- 9922249
TI  - PhaF, a polyhydroxyalkanoate-granule-associated protein of Pseudomonas oleovorans
      GPo1 involved in the regulatory expression system for pha genes.
AB  - The phaC1 gene codes for the medium-chain-length polyhydroxyalkanoate (mcl PHA)
      synthase of Pseudomonas oleovorans GPo1, which produces mcl PHA when grown in an
      excess of carbon source and under nitrogen limitation. In this work, we have
      demonstrated, by constructing a recombinant P. oleovorans strain carrying a
      phaC1::lacZ reporter system, that the phaC1 gene is expressed efficiently in the
      presence of octanoic acid while its expression is repressed when glucose or
      citrate is used as the carbon source. Moreover, a P. oleovorans GPo1 mutant
      (strain GPG-Tc6) expressing higher levels of the reporter gene than the wild-type
      strain in the presence of glucose or citrate has been generated by mini-Tn5
      insertional mutagenesis. Characterization of this mutant allowed us to conclude
      that phaF, a gene located downstream of the pha gene cluster, was knocked out in
      this strain. P. oleovorans GPG-Tc6 regained the ability to control phaC1 gene
      expression when complemented with the phaF wild-type gene. Sequencing data
      revealed the presence of three complete open reading frames (ORFs) in this
      region: ORF1 and phaI and phaF genes. The amino acid sequences of the phaI gene
      product and the N-terminal half of the PhaF protein showed a significant degree
      of similarity. Furthermore, the primary structure of the PhaF C terminus
      identifies this protein as a member of the histone H1-like group of proteins.
      Northern blot analysis showed two transcription units containing phaF, i.e., phaF
      and phaIF transcripts. Expression of the phaIF operon is more efficient in the
      presence of octanoic acid and is enhanced by the lack of the PhaF protein. In
      addition, it has also been demonstrated that both PhaF and PhaI proteins are
      bound to PHA granules produced by P. oleovorans. A model for the role of PhaF in
      regulating PHA synthesis is presented.

PMID- 9922247
TI  - Biosynthesis of the pyrimidine moiety of thiamine independent of the PurF enzyme
      (Phosphoribosylpyrophosphate amidotransferase) in Salmonella typhimurium:
      incorporation of stable isotope-labeled glycine and formate.
AB  - Genetic analyses have suggested that the pyrimidine moiety of thiamine can be
      synthesized independently of the first enzyme of de novo purine synthesis,
      phosphoribosylpyrophosphate amidotransferase (PurF), in Salmonella typhimurium.
      To obtain biochemical evidence for and to further define this proposed synthesis,
      stable isotope labeling experiments were performed with two compounds, [2
      13C]glycine and [13C]formate. These compounds are normally incorporated into
      thiamine pyrophosphate (TPP) via steps in the purine pathway subsequent to PurF.
      Gas chromatography-mass spectrometry analyses indicated that both of these
      compounds were incorporated into the pyrimidine moiety of TPP in a purF mutant.
      This result clearly demonstrated that the pyrimidine moiety of thiamine was being
      synthesized in the absence of the PurF enzyme and strongly suggested that this
      synthesis utilized subsequent enzymes of the purine pathway. These results were
      consistent with an alternative route to TPP that bypassed only the first enzyme
      in the purine pathway. Experiments quantitating cellular thiamine monophosphate
      (TMP) and TPP levels suggested that the alternative route to TPP did not function
      at the same capacity as the characterized pathway and determined that levels of
      TMP and TPP in the wild-type strain were significantly altered by the presence of
      purines in the medium.

PMID- 9922250
TI  - Functional analysis of a rickettsial OmpA homology domain of Shigella flexneri
      icsA.
AB  - Shigella flexneri is a gram-negative bacterium that causes diarrhea and dysentery
      by invasion and spread through the colonic epithelium. Bacteria spread by
      assembling actin and other cytoskeletal proteins of the host into "actin tails"
      at the bacterial pole; actin tail assembly provides the force required to move
      bacteria through the cell cytoplasm and into adjacent cells. The 120-kDa S.
      flexneri outer membrane protein IcsA is essential for actin assembly. IcsA is
      anchored in the outer membrane by a carboxy-terminal domain (the beta domain),
      such that the amino-terminal 706 amino acid residues (the alpha domain) are
      exposed on the exterior of the bacillus. The alpha domain is therefore likely to
      contain the domains that are important to interactions with host factors. We
      identify and characterize a domain of IcsA within the alpha domain that bears
      significant sequence similarity to two repeated domains of rickettsial OmpA,
      which has been implicated in rickettsial actin tail formation. Strains of S.
      flexneri and Escherichia coli that carry derivatives of IcsA containing deletions
      within this domain display loss of actin recruitment and increased accessibility
      to IcsA-specific antibody on the surface of intracytoplasmic bacteria. However,
      site-directed mutagenesis of charged residues within this domain results in actin
      assembly that is indistinguishable from that of the wild type, and in vitro
      competition of a polypeptide of this domain fused to glutathione S-transferase
      did not alter the motility of the wild-type construct. Taken together, our data
      suggest that the rickettsial homology domain of IcsA is required for the proper
      conformation of IcsA and that its disruption leads to loss of interactions of
      other IcsA domains within the amino terminus with host cytoskeletal proteins.

PMID- 9922252
TI  - Fibrillar array in the cell wall of a gliding filamentous cyanobacterium.
AB  - The cell walls of a number of filamentous, gliding cyanobacteria of the genus
      Oscillatoria were examined by transmission electron microscopy of ultrathin
      sections, of freeze-etched replicas, and of whole cells crushed between glass
      slides and negatively stained. All three techniques revealed the presence of a
      highly ordered array of parallel fibrils, seen in transverse sections to be
      situated between the peptidoglycan and the outer membrane. Approximately 200
      individual fibrils, each 25 to 30 nm in width, form a parallel, helical array
      that completely surrounds each cyanobacterial filament, running at an angle of 25
      to 30 degrees to its long axis. This highly regular arrangement of the fibrillar
      layer may imply some underlying symmetry responsible for its organization. A
      possible source of such symmetry would be the peptidoglycan, and some form of
      interaction between this layer and the fibrils might provide the necessary
      scaffolding for the fibrillar array. In crushed, negatively stained samples of
      fresh cells, individual fibrils were seen outside the filament, released from the
      cell wall. These released fibrils were of the same width as those observed in
      situ but were in short lengths, mostly of 100 to 200 nm, and were invariably
      bent, sometimes even into U shapes, implying great flexibility. Negative staining
      of released fibrils showed no evidence that they were hollow tubes but did give
      some indication of a substructure, implying that they were composed of many
      subunits. The function of this fibrillar array is unknown, although its position
      in the cell wall, as well as the correspondence between the angle of the fibrils
      with respect to the long axis of the filament and the rotation of the filament
      during gliding, may imply an involvement in gliding motility.

PMID- 9922251
TI  - The mutK gene of Vibrio cholerae: a new gene involved in DNA mismatch repair.
AB  - A new gene, mutK, of Vibrio cholerae, encoding a 19-kDa protein which is involved
      in repairing mismatches in DNA via a presumably methyl-independent pathway, has
      been identified. The product of the mutK gene cloned in either high- or low-copy
      number vectors can reduce the spontaneous mutation frequency of Escherichia coli
      mutS, mutL, mutU, and dam mutants. The spontaneous mutation frequency of a
      chromosomal mutK knockout mutant was almost identical to that of wild-type V.
      cholerae cells, indicating that when the methyl-directed mismatch repair is
      blocked, the repair potential of MutK becomes apparent. The complete nucleotide
      sequence of the mutK gene has been determined, and the deduced amino acid
      sequence showed three open reading frames (ORFs), of which the ORF3 represents
      the mutK gene product. The mutK gene product has no significant homology with any
      of the proteins deposited in the EMBL data bank. ORF2, located upstream of mutK,
      encodes a 14-kDa protein which has more than 70% homology with a hypothetical
      protein found only downstream of the E. coli vsr gene. ORF1, located farther
      upstream of mutK, has more than 80% homology with a major cold shock protein
      found in several bacteria. Downstream of mutK, a partial ORF having 60% homology
      with an RNA methyltransferase has been identified. The mutK gene has recently
      been positioned in the ordered cloned DNA map of the genome of the V. cholerae
      strain from which the gene was isolated (10).

PMID- 9922253
TI  - Cra-dependent transcriptional activation of the icd gene of Escherichia coli.
AB  - The icd gene of Escherichia coli, encoding isocitrate dehydrogenase, was shown to
      be expressed from two different promoters: the previously identified icd P1 and a
      newly detected second promoter, icd P2, whose expression is positively regulated
      by the catabolite repressor-activator protein Cra, formerly called FruR. In each
      case, we determined the mRNA start site by primer extension analysis of in vivo
      transcripts and examined the interaction of the icd control region with either
      RNA polymerase or Cra. We observed that (i) the Cra factor binds to and activates
      transcription from a site centered at position -76.5 within the icd P2 promoter
      region and (ii) three particular mutations in the C-terminal end of the alpha
      subunit of RNA polymerase (L262A, R265A, and N268A) considerably diminish
      transcription initiating from the icd P2 promoter, as shown by in vitro
      experiments performed in the presence of mutant RNA polymerases carrying Ala
      substitutions.

PMID- 9922254
TI  - Sequence and function of LuxU: a two-component phosphorelay protein that
      regulates quorum sensing in Vibrio harveyi.
AB  - Vibrio harveyi regulates the expression of bioluminescence (lux) in response to
      cell density, a phenomenon known as quorum sensing. In V. harveyi, two
      independent quorum-sensing systems exist, and each produces, detects, and
      responds to a specific cell density-dependent autoinducer signal. The
      autoinducers are recognized by two-component hybrid sensor kinases called LuxN
      and LuxQ, and sensory information from both systems is transduced by a
      phosphorelay mechanism to the response regulator protein LuxO. Genetic evidence
      suggests that LuxO-phosphate negatively regulates the expression of luminescence
      at low cell density in the absence of autoinducers. At high cell density,
      interaction of the sensors with their cognate autoinducers results in
      dephosphorylation and inactivation of the LuxO repressor. In the present report,
      we show that LuxN and LuxQ channel sensory information to LuxO via a newly
      identified phosphorelay protein that we have named LuxU. LuxU shows sequence
      similarity to other described phosphorelay proteins, including BvgS, ArcB, and
      Ypd1. A critical His residue (His 58) of LuxU is required for phosphorelay
      function.

PMID- 9922255
TI  - Diversity of radA genes from cultured and uncultured archaea: comparative
      analysis of putative RadA proteins and their use as a phylogenetic marker.
AB  - Archaea-specific radA primers were used with PCR to amplify fragments of radA
      genes from 11 cultivated archaeal species and one marine sponge tissue sample
      that contained essentially an archaeal monoculture. The amino acid sequences
      encoded by the PCR fragments, three RadA protein sequences previously published
      (21), and two new complete RadA sequences were aligned with representative
      bacterial RecA proteins and eucaryal Rad51 and Dmc1 proteins. The alignment
      supported the existence of four insertions and one deletion in the archaeal and
      eucaryal sequences relative to the bacterial sequences. The sizes of three of the
      insertions were found to have taxonomic and phylogenetic significance.
      Comparative analysis of the RadA sequences, omitting amino acids in the
      insertions and deletions, shows a cladal distribution of species which mimics to
      a large extent that obtained by a similar analysis of archaeal 16S rRNA
      sequences. The PCR technique also was used to amplify fragments of 15 radA genes
      from uncultured natural sources. Phylogenetic analysis of the amino acid
      sequences encoded by these fragments reveals several clades with affinity,
      sometimes only distant, to the putative RadA proteins of several species of
      Crenarcheota. The two most deeply branching archaeal radA genes found had some
      amino acid deletion and insertion patterns characteristic of bacterial recA
      genes. Possible explanations are discussed. Finally, signature codons are
      presented to distinguish among RecA protein family members.

PMID- 9922256
TI  - Recovery of DNA replication in UV-irradiated Escherichia coli requires both
      excision repair and recF protein function.
AB  - After UV doses that disrupt DNA replication, the recovery of replication at
      replication forks in Escherichia coli requires a functional copy of the recF
      gene. In recF mutants, replication fails to recover and extensive degradation of
      the nascent DNA occurs, suggesting that recF function is needed to stabilize the
      disrupted replication forks and facilitate the process of recovery. We show here
      that the ability of recF to promote the recovery of replication requires that the
      disrupting lesions be removed. In the absence of excision repair, recF+ cells
      protect the nascent DNA at replication forks, but replication does not resume.
      The classical view is that recombination proteins operate in pathways that are
      independent from DNA repair, and therefore the functions of Rec proteins have
      been studied in repair-deficient cells. However, mutations in either uvr or recF
      result in failure to recover replication at UV doses from which wild-type cells
      recover efficiently, suggesting that recF and excision repair contribute to a
      common pathway in the recovery of replication.

PMID- 9922258
TI  - The amino-terminal 100 residues of the nitrogen assimilation control protein
      (NAC) encode all known properties of NAC from Klebsiella aerogenes and
      Escherichia coli.
AB  - The nitrogen assimilation control protein (NAC) from Klebsiella aerogenes or
      Escherichia coli (NACK or NACE, respectively) is a transcriptional regulator that
      is both necessary and sufficient to activate transcription of the histidine
      utilization (hut) operon and to repress transcription of the glutamate
      dehydrogenase (gdh) operon in K. aerogenes. Truncated NAC polypeptides, generated
      by the introduction of stop codons within the nac open reading frame, were tested
      for the ability to activate hut and repress gdh in vivo. Most of the NACK and
      NACE fragments with 100 or more amino acids (wild-type NACK and NACE both have
      305 amino acids) were functional in activating hut and repressing gdh expression
      in vivo. Full-length NACK and NACE were isolated as chimeric proteins with the
      maltose-binding protein (MBP). NACK and NACE released from such chimeras were
      able to activate hut transcription in a purified system in vitro, as were NACK129
      and NACE100 (a NACK fragment of 129 amino acids and a NACE fragment of 100 amino
      acids) released from comparable chimeras. A set of NACE and NACK fragments
      carrying nickel-binding histidine tags (his6) at their C termini were also
      generated. All such constructs derived from NACE were insoluble, as was NACE
      itself. Of the his6-tagged constructs derived from NACK, NACK100 was inactive,
      but NACK120 was active. Several NAC fragments were tested for dimerization.
      NACK120-his6 and NACK100-his6 were dimers in solution. MBP-NACK and MBP-NACK129
      were monomers in solution but dimerized when the MBP was released by cleavage
      with factor Xa. MBP-NACE was readily cleaved by factor Xa, but the resulting NACE
      was also degraded by the protease. However, MBP-NACE-his6 was completely
      resistant to cleavage by factor Xa, suggesting an interaction between the C and N
      termini of this protein.

PMID- 9922257
TI  - Gene duplication and multiplicity of collagenases in Clostridium histolyticum.
AB  - Clostridium histolyticum collagenase contains a number of different active
      components. Previously we have shown that colH encodes a 116-kDa collagenase
      (ColH) and a 98-kDa gelatinase. We purified a different 116-kDa collagenase
      (ColG) from the culture supernatant and sequenced its gene (colG). We also
      identified four other gelatinases (105, 82, 78, and 67 kDa) and determined their
      N-terminal amino acid sequences, all of which coincided with that of either ColG
      or ColH. Hybridization experiments showed that each gene is present in a single
      copy and each gene is transcribed into a single mRNA. These results suggest that
      all the gelatinases are produced from the respective full-length collagenase by
      the proteolytic removal of C-terminal fragments. The substrate specificities of
      the enzymes suggest that colG and colH encode class I and class II enzymes,
      respectively. Analysis of their DNA locations by pulsed-field gel electrophoresis
      and nucleotide sequencing of their surrounding regions revealed that the two
      genes are located in different sites on the chromosome. C. histolyticum colG is
      more similar to C. perfringens colA than to colH in terms of domain structure.
      Both colG and colA have a homologous gene, mscL, at their 3' ends. These results
      suggest that gene duplication and segment duplication have occurred in an
      ancestor cell common to C. histolyticum and C. perfringens and that further
      divergence of the parent gene produced colG and colA.

PMID- 9922259
TI  - Phenotypic analysis of random hns mutations differentiate DNA-binding activity
      from properties of fimA promoter inversion modulation and bacterial motility.
AB  - H-NS is a major Escherichia coli nucleoid-associated protein involved in
      bacterial DNA condensation and global modulation of gene expression. This protein
      exists in cells as at least two different isoforms separable by isoelectric
      focusing. Among other phenotypes, mutations in hns result in constitutive
      expression of the proU and fimB genes, increased fimA promoter inversion rates,
      and repression of the flhCD master operon required for flagellum biosynthesis. To
      understand the relationship between H-NS structure and function, we transformed a
      cloned hns gene into a mutator strain and collected a series of mutant alleles
      that failed to repress proU expression. Each of these isolated hns mutant alleles
      also failed to repress fimB expression, suggesting that H-NS-specific repression
      of proU and fimB occurs by similar mechanisms. Conversely, alleles encoding
      single amino acid substitutions in the C-terminal DNA-binding domain of H-NS
      resulted in significantly reduced affinity for DNA yet conferred a wild-type fimA
      promoter inversion frequency, indicating that the mechanism of H-NS activity in
      modulating promoter inversion is independent of DNA binding. Furthermore, two
      specific H-NS amino acid substitutions resulted in hypermotile bacteria, while C
      terminal H-NS truncations exhibited reduced motility. We also analyzed H-NS
      isoform composition expressed by various hns mutations and found that the N
      terminal 67 amino acids were sufficient to support posttranslational modification
      and that substitutions at positions 18 and 26 resulted in the expression of a
      single H-NS isoform. These results are discussed in terms of H-NS domain
      organization and implications for biological activity.

PMID- 9922261
TI  - NolL of Rhizobium sp. strain NGR234 is required for O-acetyltransferase activity.
AB  - Following (iso)flavonoid induction, nodulation genes of the symbiotic nitrogen
      fixing bacterium Rhizobium sp. strain NGR234 elaborate a large family of
      lipooligosaccharidic Nod factors (NodNGR factors). When secreted into the
      rhizosphere of compatible legumes, these signal molecules initiate root hair
      deformation and nodule development. The nonreducing glucosamine residue of NodNGR
      factors are N acylated, N methylated, and mono- or biscarbamoylated, while
      position C-6 of the reducing extremity is fucosylated. This fucose residue is
      normally 2-O methylated and either sulfated or acetylated. Here we present an
      analysis of all acetylated NodNGR factors, which clearly shows that the acetate
      group may occupy position C-3 or C-4 of the fucose moiety. Disruption of the
      flavonoid-inducible nolL gene, which is preceded by a nod box, results in the
      synthesis of NodNGR factors that lack the 3-O- or 4-O-acetate groups.
      Interestingly, the nodulation capacity of the mutant NGROmeganolL is not
      impaired, whereas introduction of the nod box::nolL construct into the related
      strain Rhizobium fredii USDA257 extends the host range of this bacterium to
      Calopogonium caeruleum, Leucaena leucocephala, and Lotus halophilus. Nod factors
      produced by a USDA257(pnolL) transconjugant were also acetylated. The nod
      box::nolL construct was also introduced into ANU265 (NGR234 cured of its
      symbiotic plasmid), along with extra copies of the nodD1 gene. When
      permeabilized, these cells possessed acetyltransferase activity, although crude
      extracts did not.

PMID- 9922260
TI  - EmrE, a small Escherichia coli multidrug transporter, protects Saccharomyces
      cerevisiae from toxins by sequestration in the vacuole.
AB  - In this report we describe the functional expression of EmrE, a 110-amino-acid
      multidrug transporter from Escherichia coli, in the yeast Saccharomyces
      cerevisiae. To allow for phenotypic complementation, a mutant strain sensitive to
      a series of cationic lipophilic drugs was first identified. A hemagglutinin
      epitope-tagged version of EmrE (HA-EmrE) conferring resistance to a wide variety
      of drugs, including acriflavine, ethidium, methyl viologen, and the neurotoxin 1
      methyl-4-phenylpyridinium (MPP+), was functionally expressed in this strain. HA
      EmrE is expressed in yeast at relatively high levels (0.5 mg/liter), is soluble
      in a mixture of organic solvents, and can be functionally reconstituted in
      proteoliposomes. In bacterial cells, EmrE removes toxic compounds by active
      transport through the plasma membrane, lowering their cytosolic concentration.
      However, yeast cells expressing HA-EmrE take up 14C-methyl viologen as well as
      control cells do. Thus, we investigated the basis of the enhanced resistance to
      the above compounds. Using Cu2+ ions or methylamine, we could selectively
      permeabilize the plasma membrane or deplete the proton electrochemical gradients
      across the vacuolar membrane, respectively. Incubation of yeast cells with copper
      ions caused an increase in 14C-methyl viologen uptake. In contrast, treatment
      with methylamine markedly diminished the extent of uptake. Conversely, the effect
      of Cu2+ and methylamine on a plasma membrane uptake system, proline, was
      essentially the opposite: while inhibited by the addition of Cu2+, it remained
      unaffected when cells were treated with methylamine. To examine the intracellular
      distribution of HA-EmrE, a functional chimera between HA-EmrE and the green
      fluorescent protein (HA-EmrE-GFP) was prepared. The pattern of HA-EmrE-GFP
      fluorescence distribution was virtually identical to that of the vacuolar marker
      FM 4-64, indicating that the transporter is found mainly in this organelle.
      Therefore, HA-EmrE protects yeast cells by lowering the cytoplasmic
      concentrations through removal of the toxin to the vacuole. This novel way of
      detoxification has been previously suggested to function in organisms in which a
      large vacuolar compartment exists. This report represents the first molecular
      description of such a mechanism.

PMID- 9922262
TI  - Biochemical and genetic evidence for meta-ring cleavage of 2,4, 5
      trihydroxytoluene in Burkholderia sp. strain DNT.
AB  - 2,4,5-Trihydroxytoluene (THT) oxygenase from Burkholderia sp. strain DNT
      catalyzes the conversion of THT to an unstable ring fission product. Biochemical
      and genetic studies of THT oxygenase were undertaken to elucidate the mechanism
      of the ring fission reaction. The THT oxygenase gene (dntD) was previously
      localized to the 1.2-kb DNA insert subcloned in the recombinant plasmid
      designated pJS76 (W. C. Suen and J. C. Spain, J. Bacteriol. 175:1831-1837, 1993).
      Analysis of the deduced amino acid sequence of DntD revealed the presence of the
      highly conserved residues characteristic of the catechol 2,3-dioxygenase gene
      family I. The deduced amino acid sequence of DntD corresponded to a molecular
      mass of 35 kDa. The native molecular masses for the THT oxygenase estimated by
      using gel filtration chromatography and nondenaturing gel electrophoresis were
      67.4 and 77.8 kDa, respectively. The results suggested that the native protein
      consists of two identical subunits. The colorless protein contained 2 mol of iron
      per mol of protein. Stimulation of activity in the presence of ferrous iron and
      ascorbate suggested a requirement for ferrous iron in the active site. The
      properties of the enzyme are similar to those of the catechol 2,3-dioxygenases
      (meta-cleavage dioxygenases). In addition to THT, the enzyme exhibited activity
      towards 1,2,4-benzenetriol, catechol, 3- and 4-methylcatechol, and 3- and 4
      chlorocatechol. The chemical analysis of the THT ring cleavage product showed
      that the product was 2, 4-dihydroxy-5-methyl-6-oxo-2,4-hexadienoic acid,
      consistent with extradiol ring fission of THT.

PMID- 9922263
TI  - Effect of wzx (rfbX) mutations on A-band and B-band lipopolysaccharide
      biosynthesis in Pseudomonas aeruginosa O5.
AB  - The wbp cluster of Pseudomonas aeruginosa O5 encodes a number of proteins
      involved in biosynthesis of the heteropolymeric and Wzy-dependent B-band O
      antigen, including Wzy, the O-antigen polymerase, and Wzz, the regulator of O
      antigen chain length. A gene (formerly wbpF), contiguous with wzy in the wbp
      cluster, is predicted to encode a highly hydrophobic protein with multiple
      membrane-spanning domains. This secondary structure is consistent with that of
      Wzx (RfbX), the putative O-antigen unit translocase or "flippase." Insertion of a
      Gmr cassette at two separate sites within the putative wzx gene led in both cases
      to the loss of B-band lipopolysaccharide (LPS) O-antigen production. To our
      knowledge, this is the first report of the successful generation of chromosomal
      wzx gene replacement mutations. Surprisingly, inactivation of wzx also led to a
      marked delay in production of the ATP-binding cassette-transporter-dependent, D
      rhamnose homopolymer, A-band LPS. This effect on A-band LPS synthesis was
      alleviated by supplying multiple copies of WbpL in trans. WbpL, a WecA (Rfe)
      homologue, was shown recently to be essential for the initiation of both A-band
      and B-band LPS synthesis in P. aeruginosa O5 (H. L. Rocchetta, L. L. Burrows, J.
      C. Pacan, and J. S. Lam, Mol. Microbiol. 28:1103-1119, 1998). These results
      suggest that the delay in A-band LPS production may arise from insufficient
      access to WbpL when the completed B-band O unit is not successfully translocated
      to the periplasm. Without adequate WbpL, A-band LPS synthesis is delayed. A
      subset of wzx mutants appeared to have accumulated second-site mutations which
      either restored the normal expression of A-band LPS or abolished A-band
      expression completely. Complementation studies showed that all of the additional
      mutations affecting LPS synthesis that were characterized in this study were
      located within the B-band LPS genes.

PMID- 9922264
TI  - Cell density-dependent starvation survival of Rhizobium leguminosarum bv.
      phaseoli: identification of the role of an N-acyl homoserine lactone in
      adaptation to stationary-phase survival.
AB  - The cell density dependence of stationary-phase survival of Rhizobium
      leguminosarum has been investigated. Following starvation by exhaustion of carbon
      or nitrogen, but not of phosphorus, the survival of cultures was dependent on the
      cell density at entry into stationary phase. High-density cultures survived with
      little or no loss of viability over a 20-day period in stationary phase. In
      contrast, low-density cultures lost viability rapidly but consisted of a
      heterogeneous population, a small fraction of which successfully adapted and
      eventually formed a stable, surviving population. The threshold density above
      which the cultures survived successfully in stationary phase was dependent on the
      growth conditions and the strain used. We took advantage of the fact that R.
      leguminosarum survives poorly following starvation by resuspension in carbon-free
      medium to demonstrate that cell density-dependent survival was mediated by a
      component accumulating in the growth medium. The effects of this medium component
      on survival in resuspension assays could be mimicked by an N-acyl homoserine
      lactone, N-(3R-hydroxy-7-cis-tetradecanoyl)-L-homoserine lactone, previously
      demonstrated to have a role in controlling cell density-dependent phenomena in R.
      leguminosarum. The Sym plasmids pRP2JI and pRL1JI were found to be essential for
      the production of the extracellular factor, which could also be made in
      Escherichia coli carrying the cosmid clone pIJ1086 containing a specific region
      of pRL1JI.

PMID- 9922265
TI  - High-molecular-mass multi-c-heme cytochromes from Methylococcus capsulatus bath.
AB  - The polypeptide and structural gene for a high-molecular-mass c-type cytochrome,
      cytochrome c553O, was isolated from the methanotroph Methylococcus capsulatus
      Bath. Cytochrome c553O is a homodimer with a subunit molecular mass of 124,350 Da
      and an isoelectric point of 6. 0. The heme c concentration was estimated to be
      8.2 +/- 0.4 mol of heme c per subunit. The electron paramagnetic resonance
      spectrum showed the presence of multiple low spin, S = 1/2, hemes. A degenerate
      oligonucleotide probe synthesized based on the N-terminal amino acid sequence of
      cytochrome c553O was used to identify a DNA fragment from M. capsulatus Bath that
      contains occ, the gene encoding cytochrome c553O. occ is part of a gene cluster
      which contains three other open reading frames (ORFs). ORF1 encodes a putative
      periplasmic c-type cytochrome with a molecular mass of 118, 620 Da that shows
      approximately 40% amino acid sequence identity with occ and contains nine c-heme
      binding motifs. ORF3 encodes a putative periplasmic c-type cytochrome with a
      molecular mass of 94, 000 Da and contains seven c-heme-binding motifs but shows
      no sequence homology to occ or ORF1. ORF4 encodes a putative 11,100-Da protein.
      The four ORFs have no apparent similarity to any proteins in the GenBank
      database. The subunit molecular masses, arrangement and number of hemes, and
      amino acid sequences demonstrate that cytochrome c553O and the gene products of
      ORF1 and ORF3 constitute a new class of c-type cytochrome.

PMID- 9922267
TI  - A family of telomere-associated autonomously replicating sequences and their
      functions in targeted recombination in Hansenula polymorpha DL-1.
AB  - A family of multiple autonomously replicating sequences (ARSs) which are located
      at several chromosomal ends of Hansenula polymorpha DL-1 has been identified and
      characterized. Genomic Southern blotting with an ARS, HARS36, originating from
      the end of a chromosome, as a probe showed several homologues in the genome of H.
      polymorpha. Nucleotide sequences of the three fragments obtained by a selective
      cloning for chromosomal ends were nearly identical to that of HARS36. All three
      fragments harbored an ARS motif and ended with 18 to 23 identical repetitions of
      5'-GGGTGGCG-3' which resemble the telomeric repeat sequence in other eukaryotes.
      Transformation of H. polymorpha with nonlinearized plasmids containing the newly
      obtained telomeric ARSs almost exclusively resulted in the targeted integration
      of a single copy or multiple tandem copies of the plasmid into the chromosomes.
      The sensitivity to exonuclease Bal31 digestion of the common DNA fragment in all
      integrants confirmed the telomeric origin of HARS36 homologues, suggesting that
      several chromosomal ends, if not all of them, consisted of the same ARS motif and
      highly conserved sequences observed in HARS36. Even though the frequencies of
      targeted recombination were varied among the ends of the chromosomes, the overall
      frequency was over 96%. The results suggested that the integration of the
      plasmids containing telemeric ARSs occurred largely through homologous
      recombination at the telomeric repeats, which serve as high-frequency
      recombination targets.

PMID- 9922266
TI  - The SPI-3 pathogenicity island of Salmonella enterica.
AB  - Pathogenicity islands are chromosomal clusters of pathogen-specific virulence
      genes often found at tRNA loci. We have determined the molecular genetic
      structure of SPI-3, a 17-kb pathogenicity island located at the selC tRNA locus
      of Salmonella enterica serovar Typhimurium. The G+C content of SPI-3 (47.5%)
      differs from that of the Salmonella genome (52%), consistent with the notion that
      these sequences have been horizontally acquired. SPI-3 harbors 10 open reading
      frames organized in six transcriptional units, which include the previously
      described mgtCB operon encoding the macrophage survival protein MgtC and the Mg2+
      transporter MgtB. Among the newly identified open reading frames, one exhibits
      sequence similarity to the ToxR regulatory protein of Vibrio cholerae and one is
      similar to the AIDA-I adhesin of enteropathogenic Escherichia coli. The
      distribution of SPI-3 sequences varies among the salmonellae: the right end of
      the island, which harbors the virulence gene mgtC, is present in all eight
      subspecies of Salmonella; however, a four-gene cluster at the center of SPI-3 is
      found in only some of the subspecies and is bracketed by remnants of insertion
      sequences, suggesting a multistep process in the evolution of SPI-3 sequences.

PMID- 9922269
TI  - Characterization of IS1547, a new member of the IS900 family in the Mycobacterium
      tuberculosis complex, and its association with IS6110.
AB  - Unlike classically defined insertion sequence (IS) elements, which are delimited
      by their inverted terminal repeats, some IS elements do not have inverted
      terminal repeats. Among this group of atypical IS elements, IS116, IS900, IS901,
      and IS1110 have been proposed as members of the IS900 family of elements, not
      only because they do not have inverted terminal repeats but also because they
      share other features such as homologous transposases and particular insertion
      sites. In this study, we report a newly identified IS sequence, IS1547, which was
      first identified in a clinical isolate of Mycobacterium tuberculosis. Its
      structure, insertion site, and putative transposase all conform with the
      conventions of the IS900 family, suggesting that it is a new member of this
      family. IS1547 was detected only in isolates of the M. tuberculosis complex,
      where it had highly polymorphic restriction fragment length polymorphism
      patterns, suggesting that it may be a useful genetic marker for identifying
      isolates of the M. tuberculosis complex and for distinguishing different strains
      of M. tuberculosis. ipl is a preferential locus for IS6110 insertion where there
      are eight known different insertion sites for IS6110. Surprisingly, the DNA
      sequence of ipl is now known to be a part of IS1547, meaning that IS1547 is a
      preferential site for IS6110 insertion.

PMID- 9922268
TI  - IS6110-mediated deletions of wild-type chromosomes of Mycobacterium tuberculosis.
AB  - The ipl locus is a site for the preferential insertion of IS6110 and has been
      identified as an insertion sequence, IS1547, in its own right. Various deletions
      around the ipl locus of clinical isolates of Mycobacterium tuberculosis were
      identified, and these deletions ranged in length from several hundred base pairs
      up to several kilobase pairs. The most obvious feature shared by these deletions
      was the presence of an IS6110 copy at the deletion sites, which suggested two
      possible mechanisms for their occurrence, IS6110 transposition and homologous
      recombination. To clarify the mechanism, an investigation was conducted; the
      results suggest that although deletion transpositionally mediated by IS6110 was a
      possibility, homologous recombination was a more likely one. The implications of
      such chromosomal rearrangements for the evolution of M. tuberculosis, for IS6110
      mediated mutagenesis, and for the development of genetic tools are discussed. The
      deletion of genomic DNA in isolates of M. tuberculosis has previously been noted
      at only a few sites. This study examined the deletional loss of genetic material
      at a new site and suggests that such losses may occur elsewhere too and may be
      more prevalent than was previously thought. Distinct from the study of laboratory
      induced mutations, the detailed analysis of clinical isolates, in combination
      with knowledge of their evolutionary relationships to each other, gives us the
      opportunity to study mutational diversity in isolates that have survived in the
      human host and therefore offers a different perspective on the importance of
      particular genetic markers in pathogenesis.

PMID- 9922270
TI  - Cloning and characterization of a gene (mspA) encoding the major sheath protein
      of Treponema maltophilum ATCC 51939(T).
AB  - The major sheath protein-encoding gene (mspA) of the oral spirochete Treponema
      maltophilum ATCC 51939(T) was cloned by screening a genomic library with an anti
      outer membrane fraction antibody. The mspA gene encodes a precursor protein of
      575 amino acids with a predicted molecular mass of 62.3 kDa, including a signal
      peptide of 19 amino acids. The native MspA formed a heat-modifiable, detergent-
      and trypsin-stable complex which is associated with the outer membrane.
      Hybridization with an mspA-specific probe showed no cross-reactivity with the msp
      gene from Treponema denticola.

PMID- 9922271
TI  - The udhA gene of Escherichia coli encodes a soluble pyridine nucleotide
      transhydrogenase.
AB  - The udhA gene of Escherichia coli was cloned and expressed in E. coli and found
      to encode an enzyme with soluble pyridine nucleotide transhydrogenase activity.
      The N-terminal end of the enzyme contains the fingerprint motif of a dinucleotide
      binding domain, not present in published E. coli genome sequences due to a
      sequencing error. E. coli is hereby the first organism reported to possess both a
      soluble and a membrane-bound pyridine nucleotide transhydrogenase.

PMID- 9922272
TI  - Archaeal nucleosome positioning by CTG repeats.
AB  - DNA shape recognition determines the preferred binding sites for sequence
      independent DNA binding proteins, and here we document that archaeal histones
      assemble archaeal nucleosomes in vitro centered preferentially within (CTG)6 and
      (CTG)8 repeats, close to junctions with flanking mixed-sequence DNA. Archaeal
      nucleosomes were not positioned by (CTG)4-, (CTG)5-, or (CTG)3AA(CTG)3-containing
      DNA sequences. The features of CTG repeat-containing sequences that direct
      eucaryal nucleosome positioning may also be similarly recognized by archaeal
      histones.

PMID- 9922273
TI  - Topology of RbsC, a membrane component of the ribose transporter, belonging to
      the AraH superfamily.
AB  - RbsC of Escherichia coli is the hydrophobic membrane component of ribose uptake
      system classified as the ATP-binding cassette transporter. To understand the
      structure and function of RbsC, its transmembrane topology was investigated by
      using 64 RbsC-PhoA fusions isolated either specifically or randomly. In order to
      confirm the cytoplasmic location of the short C-terminal region (5 amino acids),
      inside-out or right-side-out membrane vesicles were generated, and the C-terminal
      region was found to be digested by carboxypeptidase A only in inside-out
      vesicles. This result is consistent with the model, based on the results of
      alkaline phosphatase fusions, in which the protein traverses the membrane six
      times and the N and C termini are exposed to the cytoplasm.

PMID- 9922275
TI  - Genetic transfer of large DNA inserts to designated loci of the Bacillus subtilis
      168 genome.
AB  - It was found that contiguous DNA segments of up to 50 kb can be transferred
      between Bacillus subtilis genomes when a sufficient length of the flanking
      genomic region is provided for homologous recombination, although the efficiency
      of transfer was reduced as the insert size increased. Inserts were translocated
      to different loci, where appropriate integration sites were created.

PMID- 9922274
TI  - Escherichia coli cells exposed to streptomycin display a mutator phenotype.
AB  - Mistranslation mediated by the mutA and mutC tRNA alleles elicits a strong
      mutator phenotype (H. S. Murphy and M. Z. Humayun, J. Bacteriol. 179:7507-7514,
      1997; M. M. Slupska, C. Baikalov, R. Lloyd, and J. H. Miller, Proc. Natl. Acad.
      Sci. USA 93:4380-4385, 1996). Here, we show that exposure to streptomycin, an
      antibiotic known to promote mistranslation, induces a recA- and umuDC-independent
      mutator phenotype detected as enhanced mutagenesis at a 3, N4-ethenocytosine
      lesion borne on transfected M13 single-stranded DNA.

PMID- 9922276
TI  - Sporadic distribution of tRNA(Arg)CCU introns among alpha-purple bacteria:
      evidence for horizontal transmission and transposition of a group I intron.
AB  - A group I intron interrupts the tRNA(Arg)CCU gene of the alpha-purple bacterium
      Agrobacterium tumefaciens (B. Reinhold-Hurek and D. A. Shub, Nature [London]
      357:173-176, 1992). In this study, we assess the distribution of the
      corresponding intron among 12 additional species of alpha-purple bacteria. Of 10
      newly identified tRNA(Arg)CCU genes, we found only two that contained an intron
      homologous to that of the Agrobacterium intron. This restricted and scattered
      distribution of the tRNA(Arg)CCUg intron among alpha-purple bacteria is
      consistent with a recent origin and horizontal transmission. Primary and
      secondary structural similarities between tRNA(Leu)UAA introns found in strains
      of the cyanobacterium Microcystis aeruginosa (K. Rudi and K. S. Jacobsen, FEMS
      Microbiol. Lett. 156:293-298, 1997) and alpha-purple tRNA(Arg)CCU introns suggest
      that these introns share a more recent common ancestor than either does with
      other known cyanobacterial tRNA(Leu)UAA introns.

PMID- 9922278
TI  - Moving beyond fear: lessons learned through a longitudinal review of the
      literature regarding health care providers and the care of people with HIV/AIDS.
AB  - This article examines the literature regarding the health care provider/AIDS
      patient relationship for a 14 year period from 1984 through 1998. For each of the
      four time periods (1984-1989, 1990-1992, 1992-1995, 1996-1998), we present the
      general themes and concerns of the literature at that time. We begin the review
      of each time period with a depiction of what was happening in biomedical circles
      and in the broader society around HIV/AIDS. To provide a closer look at the
      setting for the work completed within each time period, we draw on research
      interviews conducted by the first author with nurses involved in AIDS care since
      the early days of the epidemic. Nurses'retrospective comments on what it was like
      to do the work at various times reveal the local reality and provide an important
      rationale for the work that we review. Each time period closes with a discussion
      of the lessons learned and suggestions of new possibilities for future efforts to
      enhance the well-being of both health care providers and patients with HIV/AIDS.

PMID- 9922277
TI  - Two roles for the leucine-responsive regulatory protein in expression of the
      alanine catabolic operon (dadAB) in Klebsiella aerogenes.
AB  - The lrp gene, which codes for the leucine-responsive regulatory protein (Lrp),
      was cloned from Klebsiella aerogenes W70. The DNA sequence was determined, and
      the clone was used to create a disruption of the lrp gene. The lack of functional
      Lrp led to an increased expression of the alanine catabolic operon (dad) in the
      absence of the inducer L-alanine but also to a decreased expression of the operon
      in the presence of L-alanine. Thus, Lrp is both a repressor and activator of dad
      expression. Lrp is also necessary for glutamate synthase formation but not for
      the formation of two other enzymes controlled by the nitrogen regulatory (Ntr)
      system, glutamate dehydrogenase and histidase.

PMID- 9922279
TI  - The complex realities of primary prevention for HIV infection in a "just do it"
      world.
AB  - Primary prevention of HIV requires behavior changes to decrease the risk of
      sexual, drug using, and occupational exposure to infection. The difficulties
      associated with behavior change are related to social, cultural, and political
      constraints that reinforce heterosexism, sexism, and racism. These problems are
      compounded by concurrent epidemics of violence, poverty, and drug use, and are
      made more difficult by the absolutist mentality. Use of theory-based
      interventions, awareness of community attributes, and a change to pragmatic
      political agendas can help in the development of effective prevention programs.

PMID- 9922280
TI  - Primary care and case management of persons with HIV/AIDS.
AB  - The nurse practitioner can meet the multiple needs of people living with HIV
      disease. Given the broad scope and integration of services required to care for
      clients with HIV/AIDS, the skill of a nursing case manager is also an integral
      part of the health care team. Together, these nursing clinicians can enhance the
      quality of care provided to HIV-infected individuals as each plays numerous roles
      with specific competencies and skills. This article discusses primary care
      services and the role of health care providers in working with persons with
      HIV/AIDS.

PMID- 9922281
TI  - State of the art: antiretroviral and prophylactic treatments in HIV/AIDS.
AB  - HIV results in a continual and progressive pathological attack on the human
      immune system. This attack on the immune system can be altered with combination
      antiretroviral agents that interrupt the HIV life-cycle. There are three classes
      of approved antiretroviral agents: nucleoside reverse transcriptase inhibitors,
      nonnucleoside reverse transcriptase inhibitors, and protease inhibitors. The
      progressive deterioration of the patient's immune system by HIV infection
      increases the likelihood of developing opportunistic infections. Primary measures
      that can be taken to prevent the development of opportunistic infections are
      preventing exposure to the microorganisms in the environment and maintaining a
      competent immune system using antiretroviral therapy through prophylactic agents
      specific to opportunistic infections.

PMID- 9922282
TI  - Adherence to highly active antiretroviral therapy.
AB  - Advances in scientific understanding of and pharmacologic therapies for HIV
      infection have significantly increased the potential benefits of medical
      regimens. Patients adherence to these regimens is an essential antecedent to
      therapeutic effectiveness. Nursing interventions to improve adherence target the
      patient, the clinician, and the regimen.

PMID- 9922283
TI  - Palliative care: pain and symptom management in persons with HIV/AIDS.
AB  - As patients with HIV/AIDS are living longer with the illness, pain and symptom
      management are increasingly important health issues. This article will discuss
      the assessment and management of such common problems as pain, fatigue and
      weakness, dyspnea and cough, anorexia and weight-loss, nausea and vomiting, sleep
      disorders, dry mouth, diarrhea, itching, and fever and night sweats.

PMID- 9922285
TI  - Grief work of HIV positive persons and their survivors.
AB  - Grief and bereavement following the death of a loved one present clients with
      significant challenges to the physical, emotional, and spiritual health and well
      being. The grieving process for the person with HIV infection may be compounded
      by shame, stigma, and lack of social support. For communities with the highest
      prevalence of HIV infection, AIDS-related losses have resulted in mounting, and
      often overlapping, bereavements. Addressing the impact of these bereavements on
      the physical and emotional health of clients and their survivors is imperative to
      designing appropriate interventions to alleviate the potential adverse health
      outcomes associated with epidemic loss. Facilitating the grief work of HIV
      positive persons and their loved ones serves to assuage unhealthy sequelae,
      promote effective coping skills, and provide opportunities for personal growth.

PMID- 9922284
TI  - Evaluating alternative treatments for HIV infection.
AB  - Complementary and alternative medicine (CAM) offers views of disease and its
      treatment that may not compatible with western medicine. In this review of CAM,
      the authors provide a strategy by which to evaluate CAM in advanced nursing
      practice. The strategy is shaped by critiques of how to study CAM in light of the
      relationships that nurses share with their patients. Expert nursing knowledge of
      HIV-infected patients, in combination with acquired understandings of CAM, offer
      nurses additional interventions to use in the management of HIV-related symptoms.

PMID- 9922286
TI  - The care of women with AIDS: special needs and considerations.
AB  - The growing number of women being diagnosed with HIV/AIDS mandates the need to
      focus attention on the special needs of this population. Although women have many
      of the same devastating physical manifestations of HIV infection as men do, they
      face unique psychological and social issues that influence their ability to
      respond to their disease in the same ways. Women with HIV/AIDS are
      disproportionally poor or minority women who lack resources to maintain their
      health. It is impossible to address HIV infection in women without considering
      such factors as poverty, discrimination, and gender role expectations. This
      article uses a biopsychosocial framework to discuss a range of specific issues
      affecting the health and well-being of women with HIV/AIDS.

PMID- 9922287
TI  - Home care: addressing the needs of people living with AIDS and their caregivers.
AB  - Home care has become an important community resource for the care of people
      living with AIDS (PLWA). Another important resource to maintaining PLWAs in the
      home environment is the availability of informal caregivers who are willing to
      provide support and assistance in the home setting. Because of the stressful
      nature of AIDS care, home care nurses must anticipate and address the needs of
      both PLWAs and their caregivers.

PMID- 9922288
TI  - Occupational exposure to HIV: considerations for postexposure prophylaxis and
      prevention.
AB  - HIV seroconversion as a result of an occupational exposure is a terrifying
      concern of healthcare workers who deliver care to patients in a variety of health
      care settings. In this article the most recent CDC guidelines for the management
      of HIV exposure and postexposure prophylaxis are reviewed. Prevention of
      bloodborne pathogen exposures, specifically through the selection of safety
      devices, is recognized as an important issue.

PMID- 9922289
TI  - The era of managed care: the struggle of cost containment and compassionate,
      effective care of persons with HIV/AIDS.
AB  - Managed care is an increasingly widespread way of delivering health care that
      combines medical care provider systems (doctors, nurses, clinics, hospitals) with
      the payor system (health insurance). This article gives a historical overview of
      managed health care, discusses managed HIV care, and managed care reform.

PMID- 9922291
TI  - Common anorectal symptomatology.
AB  - The primary care physician must make rapid diagnostic and therapeutic decisions
      pertaining to all body systems on a daily basis. Anorectal symptomatology
      generally is straightforward. Once the physician becomes familiar with the
      various disease processes that underlie hematochezia, anorectal pain and
      irritation, and changes in stooling habits, he or she can become more comfortable
      with managing anorectal disease in the office.

PMID- 9922290
TI  - Profiling care and benchmarking best practice in care of hospitalized elderly:
      the Geriatric Institutional Assessment Profile.
AB  - This article reports on a new instrument, the Geriatric Institutional Assessment
      Profile (GIAP), developed to assess (1) hospital workers' knowledge, attitudes,
      and perceptions regarding care of geriatric patients, and (2) the perceived
      adequacy of an institutional environment to serve geriatric patients' needs.
      Findings are reported from 303 questionnaires completed by health care employees
      from a 658-bed academic medical center. Internal consistency estimates were
      consistently high for the various components of the GIAP. Factor analysis was
      performed to examine underlying dimensions of knowledge and institutional
      environment. The GIAP has the potential to narrow the gap between actual and best
      practice in geriatric care by identifying staff information needs and concerns,
      as well as institutional barriers and facilitators to providing quality geriatric
      hospital care.

PMID- 9922292
TI  - Approach to the patient.
AB  - A systematic approach to the patient with anorectal complaints allows for an
      accurate and efficient diagnosis of the underlying problem. The process can be
      divided into the interview, the examination, treatment, and conveyance of
      information. Throughout this process, the patient must be reassured and made as
      comfortable as possible. A successful interaction with the patient leads to a
      diagnosis and a treatment plan that is acceptable to both the physician and the
      patient.

PMID- 9922293
TI  - Hemorrhoids.
AB  - Hemorrhoids are one of the most frequent anorectal disorders encountered in the
      primary care setting. They are the most common cause of hematochezia, and are
      responsible for considerable patient suffering and disability. With the
      techniques of diagnosis and office-based interventions described in this article,
      the primary care provider can effectively relieve most patients' symptoms and
      ensure that more significant bowel disease is not overlooked.

PMID- 9922294
TI  - Anorectal pain and irritation: anal fissure, levator syndrome, proctalgia fugax,
      and pruritus ani.
AB  - Anal fissures, proctalgia fugax, levator ani syndrome, and pruritus ani are
      common causes of anorectal pain and irritation. The clinician who obtains a
      thorough history and performs a complete examination can accurately diagnose
      these disorders. Ancillary tests seldom are helpful and rarely are necessary.
      Most patients suffering from these conditions readily respond to conservative
      therapy provided in the primary care practitioner's office.

PMID- 9922295
TI  - Anorectal abscess and fistula.
AB  - Anorectal abscesses and fistulas are seen commonly in the primary care practice.
      An abscess forms as the result of obstruction of an anal gland, with resulting
      retrograde infection. An anal fistula simply represents the chronic phase of a
      perianal abscess. The history generally is diagnostic, and special studies
      usually are not required. Treatment is surgical, with good results.

PMID- 9922296
TI  - Anal warts, sexually transmitted diseases, and anorectal conditions associated
      with human immunodeficiency virus.
AB  - Sexually transmitted diseases (STDs) are the cause of many different anorectal
      symptoms and complaints. Patients often present concerned that they have
      hemorrhoids. It is very important for primary care providers to be aware of the
      prevalance of anorectal STDs, common presentations, and management options. This
      article specifically addresses anal warts, gonorrhea, chlamydia, syphilis,
      herpes, and anorectal manifestations associated with HIV.

PMID- 9922298
TI  - Constipation, diarrhea, and irritable bowel syndrome.
AB  - Constipation, diarrhea, and irritable bowel syndrome are commonly encountered in
      the primary care practice. Most episodes of constipation and diarrhea are benign
      and self-limited. Patients with chronic constipation should undergo a screening
      evaluation to exclude organic disease, after which most can be managed
      successfully with dietary modification and fiber supplementation. The cause of
      chronic diarrhea usually can be discerned clinically, with irritable bowel
      syndrome, inflammatory bowel disease, and lactose intolerance being diagnosed
      most frequently. Irritable bowel syndrome is a functional gastrointestinal
      disorder characterized by abdominal pain and disordered defecation, which is
      successfully managed with a strong physician-patient relationship and periodic
      pharmacologic intervention.

PMID- 9922297
TI  - Rectal prolapse and fecal incontinence.
AB  - Rectal prolapse and fecal incontinence are problems with enormous social,
      functional, and economic significance to hundreds of thousands of people every
      year. Through a knowledgeable approach and careful diagnostic studies, many
      people can be cured or helped.

PMID- 9922299
TI  - Inflammatory bowel disease.
AB  - Although ulcerative colitis and Crohn's disease are relatively uncommon
      disorders, most primary care practices include a number of individuals with these
      diagnoses. Much of the initial evaluation and long-term care of these patients is
      managed or coordinated by their primary care physicians. A familiarity with
      current principles of diagnosis and treatment is essential. Ulcerative colitis
      and Crohn's disease are related, immunologically mediated disorders of unknown
      cause. Both are characterized by chronic relapsing courses, frequent need for
      surgical intervention, and increased colorectal cancer risk. Significant
      differences are seen between these two inflammatory bowel disease syndromes, in
      their histopathologic features, clinical manifestations, and response to
      treatment. This review focuses on the colorectal manifestations of inflammatory
      bowel disease, emphasizing clinical presentation, approach to diagnosis, medical
      and surgical management, and long-term prognosis.

PMID- 9922300
TI  - Anorectal miscellany: pilonidal disease, anal cancer, Bowen's and Paget's
      diseases, foreign bodies, and hidradenitis suppurativa.
AB  - Pilonidal disease commonly is seen by all primary care practitioners, and
      guidelines for office management and referral are provided. Less commonly seen
      entities, such as hidradenitis suppurativa, anal cancer, and Bowen's and Paget's
      diseases, also may affect this anatomic area. Knowledge that they may be
      encountered here helps guide the practitioner to the proper diagnosis and
      management. Lastly, foreign bodies are sometimes seen in the anorectal area, and
      information about appropriate steps to take are outlined.

PMID- 9922301
TI  - Colorectal cancer screening.
AB  - Colorectal cancer is the second most lethal cancer in the United States. The
      lifetime risk of developing colorectal cancer in the United States is 5%. Early
      detection decreases mortality, and involves stratifying individuals by risk
      factors. Clinicians can use several methods for detection and surveillance of
      colorectal cancer including the digital rectal exam (DRE), fecal occult-blood
      test (FOBT), flexible sigmoidoscopy, colonoscopy, and double contrast barium
      enema. Several groups offer guidelines recommending specific screening techniques
      and intervals. In general, a combination of an annual FOBT and a flexible
      sigmoidoscopy every 5 years is recommended for average-risk individuals.
      Colonoscopy is the gold standard for visualizing the entire colon, and is
      reserved for abnormal findings on FOBT or flexible sigmoidoscopy or for
      individuals of greater-than-average risk for colorectal cancer.

PMID- 9922302
TI  - Rebound hypersecretion after omeprazole and its relation to on-treatment acid
      suppression and Helicobacter pylori status.
AB  - BACKGROUND & AIMS: There have been conflicting reports regarding acid secretion
      after treatment with omeprazole. This study examined acid secretion after
      treatment with omeprazole and its relation to Helicobacter pylori status and on
      treatment gastric function. METHODS: Twelve H. pylori-negative and 9 H. pylori
      positive subjects were examined before, on, and at day 15 after an 8-week course
      of 40 mg/day omeprazole. On each occasion, plasma gastrin, intragastric pH, and
      acid output were measured basally and in response to increasing doses of gastrin
      17. RESULTS: In the H. pylori-negative subjects at day 15 after omeprazole
      treatment, basal acid output was 82% higher (P < 0.007) and maximal acid output
      28% higher (P < 0.003) than before omeprazole. The degree of increase in maximal
      acid output was related to both on-treatment pH and on-treatment fasting gastrin
      levels, being 48.0% in subjects with an on-treatment pH of >4 vs. 21. 0% in those
      with a pH of <4 (P < 0.02) and 49.2% in subjects with an on-treatment gastrin of
      >25 ng. L-1 vs. 19.8% in those with a fasting gastrin of <25 ng. L-1 (P < 0.006).
      At day 15 after omeprazole treatment, the H. pylori-positive subjects showed a
      heterogeneous response with some having increased acid output and others
      persisting suppression. CONCLUSIONS: Rebound acid hypersecretion occurs in H.
      pylori-negative subjects after omeprazole treatment. Its severity is related to
      the degree of elevation of pH on treatment. Persisting suppression of acid
      secretion masks the phenomenon in H. pylori-positive subjects.

PMID- 9922304
TI  - Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers.
AB  - BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs
      (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer
      development in the presence or absence of gastric neutrophils in patients
      requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and
      Helicobacter pylori were assessed in 120 patients randomized to receive placebo
      or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers
      and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients
      without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2
      of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine.
      However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%)
      taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23
      (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had
      neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P <
      0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in
      long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this
      infection might prevent NSAID-related peptic ulcers.

PMID- 9922303
TI  - The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1
      week triple therapies.
AB  - BACKGROUND & AIMS: The role of omeprazole in triple therapy and the impact of
      Helicobacter pylori resistance on treatment outcome are not established. This
      study investigated the role of omeprazole and influence of primary H. pylori
      resistance on eradication and development of secondary resistance. METHODS:
      Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori
      screening test result were randomized into 4 groups. OAC group received 20 mg
      omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20
      mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC
      (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg,
      and clarithromycin, 250 mg) groups received no omeprazole. All doses were
      administered twice daily for 1 week. H. pylori status was assessed before and
      after therapy by 13C-urea breath test. Susceptibility testing was performed at
      entry and in patients with persistent infection after therapy. RESULTS:
      Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for
      OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001).
      Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for
      amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains
      was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and
      clarithromycin resistance each developed in 12 patients: 8 treated with
      omeprazole and 16 without omeprazole. CONCLUSIONS: Addition of omeprazole
      achieves high eradication rates, reduces the impact of primary resistance, and
      may decrease the risk of secondary resistance compared with regimens containing
      only two antibiotics.

PMID- 9922305
TI  - Duodenal Helicobacter pylori infection differs in cagA genotype between
      asymptomatic subjects and patients with duodenal ulcers.
AB  - BACKGROUND & AIMS: It is unclear why only a minority of subjects infected by
      Helicobacter pylori develop duodenal ulcers (DU). The aim of this study was to
      investigate whether the number and type of H. pylori strains in the duodenum of
      patients with DU may play a critical role. METHODS: Twenty-one patients with DU
      and 20 asymptomatic subjects with antral H. pylori infection were studied. Paired
      biopsy specimens were taken from the antrum and from each quadrant of the
      duodenal bulb. Analyses included extent of duodenal gastric metaplasia, severity
      of duodenitis, bacterial density, presence of the cagA gene, and vacuolating
      cytotoxin activity. RESULTS: H. pylori was cultured from duodenal biopsy
      specimens in 95% of patients with DU and 80% of asymptomatic subjects. Both
      groups had a similar bacterial density and proportion of cagA-positive strains in
      the antrum (86% vs. 75%), but patients with DU had a 20-fold higher density of H.
      pylori and a higher proportion of cagA-positive strains in the duodenal bulb (81%
      vs. 30%). Active duodenitis was present only in patients with DU infected by cagA
      positive strains in the duodenum. CONCLUSIONS: The results suggest that a high
      density of cagA-positive strains in the duodenum with severe duodenitis are
      important determinants of DU disease.

PMID- 9922306
TI  - Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and
      serum pepsinogens: an international study. The Eurogst Study Group.
AB  - BACKGROUND & AIMS: CagA-positive Helicobacter pylori infection has been more
      closely associated with gastric disease than CagA-negative infection. This study
      evaluated whether geographic variation in the prevalence of CagA could explain
      variation in gastric cancer rates. METHODS: The Eurogast study was conducted in
      17 centers in 13 countries. Gastric cancer rates were calculated for each center,
      and serum samples from approximately 2850 subjects were assayed for
      immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C.
      RESULTS: The proportion of CagA-positive H. pylori infections varied across the
      centers, but this variation did not explain any more of the variation in gastric
      cancer rates than H. pylori alone. Subjects with CagA-positive infection had,
      however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio
      than subjects with CagA-negative infection; this pattern was observed
      consistently across the study centers. CONCLUSIONS: Variation in the
      seroprevalence of CagA did not explain geographic variation in gastric cancer
      rates any better than H. pylori alone. However, the consistent variation in
      pepsinogen levels with CagA status across the study centers supports the
      importance of the role of CagA in the development of gastric disease.

PMID- 9922307
TI  - Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and
      esophagogastric junction: prevalence and clinical data.
AB  - BACKGROUND & AIMS: Adenocarcinoma of the esophagus and esophagogastric junction
      (EGJ) is increasing, the earliest lesion being specialized intestinal metaplasia
      (SIM). This study determined the prevalence and demographic features of patients
      with SIM, dysplasia, and cancer in the esophagus and EGJ. METHODS: Two antegrade
      biopsy specimens were taken distal to the squamocolumnar junction (SCJ) and any
      tongues of pink mucosa proximal to the SCJ. Patients were categorized
      endoscopically and histologically as having long-segment (LSBE) or short-segment
      Barrett's esophagus (SSBE), EGJ-SIM, or a normal EGJ. RESULTS: Of 889 patients
      studied, 56 were undergoing esophagoduodenoscopy screening or surveillance and
      were not included in the prevalence calculation. The overall prevalence of SIM
      was 13.2%, with 1.6% LSBE, 6.0% SSBE, and 5.6% EGJ-SIM. Dysplasia or cancer was
      noted in 31% of LSBE, 10% of SSBE, and 6.4% of EGJ-SIM patients (P </= 0.043).
      Two cancers were associated with LSBE, 1 with SSBE, and 1 with EGJ-SIM. Patients
      with LSBE and SSBE were predominantly white (P </= 0.001), male (P </= 0. 009),
      and smokers (P </= 0.004), with LSBE patients having a longer history of
      heartburn (P </= 0.009). In contrast, patients with EGJ-SIM were similar in
      gender and ethnicity to the reference group, tended to be older (P </= 0.05),
      drank less alcohol (P </= 0.02), and had a higher prevalence of Helicobacter
      pylori infection (P </= 0.05). CONCLUSIONS: The prevalence of SSBE and EGJ-SIM is
      similar, but each entity is 3.5 times more prevalent than LSBE. However, the
      prevalence of dysplasia in LSBE is 2 times greater than in SSBE and 4 times
      greater than in EGJ-SIM. Demographically, EGJ-SIM patients are different from
      patients with Barrett's esophagus and have a higher prevalence of H. pylori
      infection. These data help to explain the increasing incidence of adenocarcinoma
      of the distal esophagus and EGJ.

PMID- 9922308
TI  - Prognostic factors in patients with Zollinger-Ellison syndrome and multiple
      endocrine neoplasia type 1. Groupe d'Etude des Neoplasies Endocriniennes
      Multiples (GENEM and groupe de Recherche et d'Etude du Syndrome de Zollinger
      Ellison (GRESZE).
AB  - BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are
      not well known in patients with the Zollinger-Ellison syndrome and multiple
      endocrine neoplasia type 1. These factors were retrospectively determined in 77
      patients. METHODS: Data chart review was performed. RESULTS: Median follow-up was
      102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of
      the 10 patients with large pancreatic tumors (>/=3 cm). Liver metastases
      developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without,
      and in 1 of the 4 patients with pancreatic tumors of unknown size; all had
      previously undergone surgery. The only independent factor associated with
      development of liver metastases identified by multivariate analysis was large
      pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7).
      Surgery was not selected. The probability of being free of liver metastases in
      the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10
      and 15 years. Thirteen (16.9%) patients died. The only independent factors of
      death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis
      before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk
      ratio/year, 1.08; 95% CI, 1.03-1.14). CONCLUSIONS: Large pancreatic tumors are
      predictive of the development of metachronous liver metastases, and surgery does
      not seem to prevent them.

PMID- 9922309
TI  - Oral budesonide for prevention of postsurgical recurrence in Crohn's disease. The
      IOIBD Budesonide Study Group.
AB  - BACKGROUND & AIMS: Prevention of postoperative recurrence after resection for
      Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral
      budesonide for prevention of endoscopic recurrence was evaluated in patients
      undergoing resection for ileal or ileocecal CD. METHODS: Sixty-three patients
      received budesonide and 66 received placebo in a double-blind, randomized trial
      with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3
      and 12 months. Indications for surgery were fibrostenosis (78 patients), disease
      activity (41), and other reasons (10). RESULTS: The frequency of endoscopic
      recurrence did not differ between the groups at 3 and 12 months. In patients with
      disease activity as indication for surgery, the endoscopic recurrence rate at the
      anastomosis was lower in the budesonide group at 3 months, although not
      significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047).
      There was no such difference with respect to fibrostenosis as indication for
      surgery. No differences in adverse event patterns were found between the two
      groups. CONCLUSIONS: Oral budesonide, 6 mg daily, offered no benefit in
      prevention of endoscopic recurrence after surgery for ileal/ileocecal
      fibrostenotic CD but decreased the recurrence rate in patients who had undergone
      surgery for disease activity.

PMID- 9922310
TI  - Altered tight junction structure contributes to the impaired epithelial barrier
      function in ulcerative colitis.
AB  - BACKGROUND & AIMS: Mechanisms of diarrhea in ulcerative colitis (UC) are still
      unknown. Functional and structural characterization of epithelial barrier and
      transport properties in ulcerative colitis (UC) was performed. METHODS: Inflamed
      sigmoid colon epithelium from UC patients was studied by alternating current
      impedance analysis to determine the pure epithelial resistance as a measure of
      intestinal barrier function. Tight junction (TJ) structure was investigated by
      freeze-fracture electron microscopy. RESULTS: Although total wall resistance was
      reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier
      defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2,
      which in conventional analysis is masked by an increase in subepithelial
      resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was
      paralleled by a change in epithelial cell TJ structure in UC. Strand count
      decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/-
      0.31 to 5.46 +/- 0.37 in the crypts. CONCLUSIONS: The inflamed colonic mucosa in
      UC has an impaired barrier function that is much more pronounced than previously
      assumed. An altered TJ structure contributes to this barrier defect which,
      because of increased back leak, can reduce net ion transport. Thus, a leak-flux
      mechanism contributes to the diarrhea in UC.

PMID- 9922311
TI  - Varying cecal bacterial loads influences colitis and gastritis in HLA-B27
      transgenic rats.
AB  - BACKGROUND & AIMS: Recent data support an important role of resident luminal
      bacteria in experimental colitis. We determined how altered cecal bacterial loads
      influence colitis and gastritis. METHODS: A cecal self-filling blind loop (SFBL)
      was created or the cecum was excluded from the fecal stream in specific pathogen
      free HLA-B27 transgenic (TG) rats with early colitis and in nontransgenic (nonTG)
      littermates; controls underwent sham operation (SHAM). Luminal bacterial
      concentrations were determined by culture and counting chamber. RESULTS: TG rats
      with SFBL had more severe cecal inflammation and leukocytosis than TG SHAM
      controls. TG excluded rats with low cecal bacterial loads had no cecal
      inflammation and less colitis and gastritis than SHAM controls, despite having
      normal distal colonic and gastric bacterial concentrations. Metronidazole
      attenuated cecal inflammation and eliminated Bacteroides in SFBL TG rats. NonTG
      SFBL rats had mild cecal inflammation and no gastritis and colitis. The ratio of
      total anaerobic to aerobic bacteria was 1000-fold greater in SFBL than in SHAM
      rats, with a 10,000-fold increased ratio of Bacteroides spp. to aerobes.
      CONCLUSIONS: The luminal bacterial load and composition determines the activity
      of cecal inflammation in genetically susceptible hosts. Lowering cecal bacterial
      concentrations can diminish inflammation in remote organs.

PMID- 9922312
TI  - The critical role of interleukin 4 but not interferon gamma in the pathogenesis
      of colitis in T-cell receptor alpha mutant mice.
AB  - BACKGROUND & AIMS: T-cell receptor alpha mutant (TCRalpha-/-) mice spontaneously
      develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)
      4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by
      creating IL-4- or IFN-gamma-deficient TCRalpha-/- mice. METHODS: Double-mutant
      mice were created by crossing TCRalpha-/- mice with IL-4- or IFN-gamma-deficient
      mice. Colitis was grossly and histologically assessed at 6 months of age, and the
      cytokine profile in the mesenteric lymph nodes and colons in these mice was
      analyzed. RESULTS: The lack of IL-4 dramatically suppressed the development of
      colitis at 6 months of age. In contrast, IFN-gamma-/- x TCRalpha-/- mice
      developed colitis similar to that present in TCRalpha-/- mice. Furthermore,
      proliferation of colonic epithelial cells was markedly increased in TCRalpha-/-
      mice and IFN-gamma-/- x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/-
      mice. Continuous administration of recombinant IL-4 led to increased colonic
      epithelial cell proliferation in IL-4(-/-) x TCRalpha-/- mice. CONCLUSIONS: IL-4
      plays an important role in the development of colitis in TCRalpha-/- mice. In
      contrast, severe colitis in TCRalpha-/- mice can develop in the absence of IFN
      gamma.

PMID- 9922313
TI  - Activation and peripheral expansion of murine T-cell receptor gamma delta
      intraepithelial lymphocytes.
AB  - BACKGROUND & AIMS: The intestinal epithelial compartment is populated by CD8(+)
      alpha beta and gamma delta intraepithelial lymphocytes (IELs), which monitor the
      integrity of the epithelial barrier. alpha beta IELs are activated by peptide
      antigens presented by class I major histocompatibility complex (MHC) molecules,
      but it is unclear how gamma delta IELs are activated. METHODS: G8 T-cell receptor
      (TCR) gamma delta transgenic (Tg) mice (specific for the class I MHC alloantigen,
      T22/10(b)) were crossed to class I MHC-deficient beta2-microglobulin-knockout
      (beta2m degrees) mice, and Tg+ IELs were examined for relative yields and surface
      and functional phenotype. RESULTS: Evidence for class I MHC-induced activation of
      Tg+ IELs was supported by the detection of 4-fold greater numbers of Tg+ IELs in
      G8 x beta2m+ mice that proliferated at 15-fold higher levels than IELs from G8 x
      beta2m degrees mice. However, expression of CD69, production of cytokine
      (interleukin 2 and interferon gamma), and detection of cytolytic function for
      IELs in G8 x beta2m degrees mice suggested that class I MHC was not required for
      gamma delta IEL development or maturation. CONCLUSIONS: These results suggest
      that CD8(+) TCR gamma delta IELs do not require class I MHC for development but
      support the notion that antigens presented by class I MHC molecules are involved
      in the peripheral expansion and differentiation of this subset.

PMID- 9922314
TI  - Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant
      generation, and mucosal injury in murine colitis.
AB  - BACKGROUND & AIMS: Inflammatory bowel disease is characterized by oxidative and
      nitrosative stress, leukocyte infiltration, and up-regulation of intercellular
      adhesion molecule 1 (ICAM-1) expression in the colon. Recent data show that
      oxidative and nitrosative stress in isolated enterocytes produces DNA single
      strand breaks that activate the nuclear enzyme poly(ADP-ribose) synthetase
      (PARS), resulting in depletion of intracellular energetics and increased
      paracellular permeability. The aim of the present study was to examine the in
      vivo relevance of this injury pathway. METHODS: Colitis was induced by rectal
      instillation of trinitrobenzenesulfonic acid (TNBS) in mice with a genetic
      deficiency of PARS (PARS-/-) and in wild-type littermates. RESULTS: In wild-type
      mice, TNBS treatment resulted in colonic erosion and ulceration that was
      maintained up to 7 days. Neutrophil infiltration (indicated by myeloperoxidase
      activity in the mucosa) was associated with up-regulation of ICAM-1 and high
      levels of malondialdehyde and nitrotyrosine. TNBS-treated PARS-/- mice
      experienced a similar colonic injury that was, however, completely resolved by 6
      days. Resolution of the damage was associated with absence of ICAM-1 up
      regulation, reduction of neutrophil infiltration, lipid peroxidation, and
      nitrosative damage. CONCLUSIONS: These data show that PARS plays a critical role
      in colonic inflammation possibly by regulating ICAM-1 expression, neutrophil
      recruitment, and the subsequent oxidant generation.

PMID- 9922315
TI  - Neurotransmitters modulate cytokine-stimulated interleukin 6 secretion in rat
      intestinal smooth muscle cells.
AB  - BACKGROUND & AIMS: Cytokine production by resident cells of the richly innervated
      muscularis externa may contribute to neuromuscular changes observed during
      intestinal inflammation. This study investigated neurotransmitter modulation of
      cytokine production by intestinal smooth muscle. METHODS: We measured interleukin
      (IL)-6 messenger RNA expression by reverse-transcription polymerase chain
      reaction, IL-6 by bioassay, and cyclic adenosine monophosphate by enzyme
      immunoassay in rat cultured intestinal smooth muscle cells exposed to IL-1beta,
      in the presence or absence of neurotransmitters. RESULTS: IL-1beta significantly
      increased IL-6 messenger RNA and protein. This was dose-dependently enhanced by
      vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP),
      and norepinephrine and inhibited by [LYS1,PRO2,5,ARG3,4,TYR6]VIP and propranolol,
      respectively. Forskolin mimicked the stimulatory effects of these
      neurotransmitters on IL-6 secretion, and the protein kinase inhibitor6-22 amide
      abolished the actions of VIP, CGRP, and norepinephrine, but not that of human
      recombinant IL-1beta, on IL-6 secretion. These agents each increased cyclic
      adenosine monophosphate activity in muscle substance P, and the neurokinin 1
      agonist Ac-[Arg6,Sar9,Met(O2)11] substance P(6-11) inhibited the IL-1beta-induced
      IL-6 release. CONCLUSIONS: This study shows neuropeptide and sympathetic
      modulation of IL-1beta-induced IL-6 production by intestinal smooth muscle. These
      interactions may contribute to altered muscle function during intestinal
      inflammation.

PMID- 9922316
TI  - Cellular and molecular mechanisms of dietary regulation on rat intestinal
      H+/Peptide transporter PepT1.
AB  - BACKGROUND & AIMS: Dietary regulation is one of the most important factors of
      intestinal peptide transport. However, the cellular and molecular mechanisms of
      dietary regulation of the intestinal peptide transport system remain unknown.
      This study investigated the molecular mechanism of transcriptional activation of
      intestinal peptide transporter (PepT1) gene by the dietary protein. The promoter
      region of the rat PepT1 gene was isolated and characterized. METHODS: PepT1
      messenger RNA levels were determined by Northern blot analysis. In transient
      transfection experiments, effects of amino acid and dipeptide on luciferase
      activity were investigated. RESULTS: The proximal promoter region of the rat
      PepT1 gene has a TATA-like box and a GC box sequence. The luciferase activities
      of the clone -351 RPT-LUC responded to particular amino acids (phenylalanine,
      arginine, and lysine) and dipeptides (Gly-Sar, Gly-Phe, Lys-Phe, and Asp-Lys). An
      AP-1 binding site and an amino acid-responsible element were present at -295 and 
      277 nucleotides relative to the transcription start site in this region.
      CONCLUSIONS: These results suggest that the up-regulation of dipeptide transport
      activity by dietary protein is caused by transcriptional activation of the PepT1
      gene by selective amino acids and dipeptides in the diet.

PMID- 9922318
TI  - Phenotypic expression of HFE mutations: a French study of 1110 unrelated iron
      overloaded patients and relatives.
AB  - BACKGROUND & AIMS: Two mutations have been described in the HFE gene: C282Y and
      H63D. The aim of this study was to determine the phenotype of the different HFE
      genotypes. METHODS: Clinical symptoms and iron data were examined according to
      HFE genotypes in 531 unrelated patients with unexplained liver iron overload and
      579 relatives of hemochromatotic patients. RESULTS: Non-C282Y +/+ patients did
      not markedly differ in terms of iron overload or clinical expression according to
      genotype, except for compound heterozygotes, who had slightly increased
      transferrin saturation. This contrasted with the strikingly increased expression
      in C282Y homozygotes. Similar phenotype/genotype correlations were observed in
      relatives based on serum iron test results. Family transmission of iron overload
      linked to HFE was exceptional in non-C282Y +/+ siblings and frequent in C282Y
      homozygotes. CONCLUSIONS: Iron overload in patients with the non-C282Y +/+
      genotype is mild to moderate, strikingly lower than in C282Y homozygotes, and is
      not influenced by HFE genotype, except, to a small extent, for compound
      heterozygotes. The role of H63D mutation therefore seems to be marginal.

PMID- 9922317
TI  - Liver colonization by human colon cancer cells is reduced by antisense inhibition
      of MUC2 mucin synthesis.
AB  - BACKGROUND & AIMS: Alterations in the production of epithelial mucins have been
      correlated with advanced tumor stage in the colon, but direct evidence for a role
      of specific mucin genes in liver metastasis is lacking. The current study was
      designed to establish more directly the role of MUC2 in colon cancer metastasis.
      METHODS: MUC2 levels were manipulated in highly metastatic human colon cancer
      cells using eukaryotic expression constructs designed to express a portion of
      MUC2 complementary DNA in antisense orientation. To assess the effect of MUC2
      levels on metastatic potential, liver colonization was assessed in athymic mice
      after splenic-portal inoculation. RESULTS: Stable integration of the MUC2
      antisense construct into metastatic colon cancer cells (LS LiM6) resulted in an
      80% reduction in MUC2-specific messenger RNA and a concomitant decrease in MUC2
      apomucin protein. This reduction was associated with a 50% reduction in synthesis
      of mature glucosamine-labeled mucin, almost complete inhibition of secretion of
      sialyl-LeX and sialyl-Tn antigens, and a 40% decrease in binding of colon cancer
      cells to E-selectin. Reduction in MUC2 levels was associated with a marked
      decrease in liver colonization. CONCLUSIONS: This study provides direct evidence
      that MUC2 plays an important role in colon cancer metastasis.

PMID- 9922319
TI  - Modeling the impact of interferon alfa treatment on liver fibrosis progression in
      chronic hepatitis C: a dynamic view. The Multivirc Group.
AB  - BACKGROUND & AIMS: Impact of hepatitis C treatment has never taken into account
      the dynamics of fibrosis progression. This study assessed the impact of
      interferon on liver fibrosis progression in patients with chronic hepatitis C
      according to 3-month aminotransferase activity response. METHODS: We recruited
      287 patients, 185 treated and 102 control, with paired biopsy specimens. Before
      follow-up, the fibrosis progression rate per year was estimated as the ratio
      between fibrosis stage in METAVIR units (1 U, 1 stage; 4 U, cirrhosis) and the
      duration of infection. During follow-up, fibrosis progression was assessed by the
      observed difference between stages divided by duration between biopsies. RESULTS:
      The median fibrosis progression rate in treated patients decreased compared with
      the rate before treatment from 0.103 F METAVIR U/yr (95% confidence interval
      [CI], 0.087-0.120) to 0.000 (95% CI, 0.000-0.000; P </= 0.0001). Among 91 treated
      responders, fibrosis stage worsened in 19 (22%), compared with 21 (22%) of 94
      treated nonresponders and 57 of 102 controls (56%; P </= 0.0001 compared with
      treated patients), and improved in 26 (29%), 17 (18%), and 8 (8%; P = 0.0002
      compared with 29% and P = 0.03 compared with 18%), respectively. These observed
      differences persisted after genotype, viremia, sex, age at infection, duration of
      infection, and alcohol consumption were taken into account. CONCLUSIONS:
      Interferon treatment changes the natural fibrosis progression rate in patients
      with chronic hepatitis C independently of genotype and early response.

PMID- 9922320
TI  - Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and
      portal veins in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Patients with cirrhosis are characterized by a reduced
      splanchnic vascular resistance and a hyporeactivity to adrenergic
      vasoconstrictors. So far, their adrenergic splanchnic vascular responsiveness has
      not been evaluated in vitro. We compared responses to alpha1- and beta2
      adrenoceptor stimulation of hepatic arteries and portal veins of patients with
      cirrhosis undergoing transplantation with those of organ donors. METHODS:
      Isometric contractions of endothelium-denuded vessel rings were induced
      cumulatively by methoxamine and relaxations by isoproterenol. Results are
      expressed as percentage of the contraction obtained by 85 mmol/L KCl or of the
      relaxation obtained by 100 micromol/L papaverine, respectively. RESULTS: Maximal
      methoxamine-induced contractions were reduced in cirrhotic hepatic arteries
      (cirrhosis, 51.8% +/- 6.8%; donor, 89.9% +/- 6.6%; P < 0.01) and portal veins
      (cirrhosis, 49.2% +/- 6.4%; donor, 94.0% +/- 5.3%; P < 0.01). In cirrhosis,
      isoproterenol induced a less marked relaxation of hepatic arteries (cirrhosis,
      46.6% +/- 3.2%; donor, 100.3% +/- 4.4%; P < 0. 01) but an increased relaxation of
      portal veins (cirrhosis, 41.9% +/- 6.2%; donor, 26.2% +/- 2.8%; P < 0.01).
      CONCLUSIONS: In cirrhosis, endothelium-free hepatic arteries are hyporeactive to
      alpha1- and beta2-adrenoceptor agonists, and portal veins are hyporeactive to
      alpha1- but hyperreactive to beta2-adrenoceptor agonists. These findings support
      the in vivo findings of a hyporesponsiveness to adrenergic vasoconstrictors in
      patients with cirrhosis.

PMID- 9922321
TI  - p16(INK4) is inactivated by extensive CpG methylation in human hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: The molecular status of the p16(INK4) tumor-suppressor gene
      has not been fully elucidated in hepatocellular carcinoma. The aim of this study
      was to clarify the mechanism that gives rise to inactivation of p16(INK4) in
      hepatocellular carcinoma. METHODS: The status of p16(INK4) was evaluated in 60
      hepatocellular carcinomas by immunohistochemical staining, differential
      polymerase chain reaction, single-strand conformational polymorphism, methylation
      specific polymerase chain reaction, and methylation-sensitive single nucleotide
      primer extension. RESULTS: Immunohistochemical staining showed that 29 of the 60
      tumors exhibited complete loss of p16(INK4) expression. High levels of DNA
      methylation were detected in 24 of 29 cases of hepatocellular carcinoma with
      negative p16(INK4) expression, with methylation of 60%-85% of the CpG islands. In
      contrast, the level of methylation was <25% in tumors with faint p16(INK4)
      staining, and no methylation was detected in tumors with positive immunostaining.
      Intragenic alteration of p16(INK4) was detected in 4 cases. CONCLUSIONS: A strong
      correlation was found between the extent of methylation and the degree of
      expression of p16(INK4) in tumor tissues, indicating that epigenetic change due
      to extensive CpG methylation is the main cause of inactivation of p16(INK4) in
      hepatocellular carcinoma.

PMID- 9922322
TI  - Regulation of the multidrug resistance protein 2 in the rat liver by
      lipopolysaccharide and dexamethasone.
AB  - BACKGROUND & AIMS: Endotoxin lipopolysaccharide (LPS) induces cholestasis and
      down-regulates the multidrug resistance protein 2 (MRP2). This study intends to
      characterize the short-term effects of LPS on MRP2. METHODS: The effects of LPS
      and dexamethasone on excretion of bromosulphalein (BSP), MRP2 messenger RNA
      (mRNA) levels, and subcellular MRP2 localization were studied by means of liver
      perfusion, Northern blots, and confocal microscopy. RESULTS: LPS treatment for 3
      12 hours decreased biliary BSP excretion (10 micromol/L) by 40%. Hyposmolarity
      stimulated BSP excretion to control levels 3 hours after LPS injection, but was
      ineffective after 12 hours or in saline-treated controls. LPS led to a strong
      decrease of MRP2 mRNA after 12 hours, but not during the first 6 hours. LPS
      induced the appearance of MRP2 in intracellular vesicles in the immediate
      vicinity of the canaliculi within 3 hours, and these vesicles were remote from
      the canaliculi after 6 and 12 hours. The MRP2-containing vesicles did not stain
      for dipeptidylpeptidase IV (DPPIV). Dexamethasone counteracted the LPS effects on
      MRP2 mRNA levels, subcellular distribution, and BSP excretion. CONCLUSIONS: LPS
      induces cholestasis due to an early retrieval of MRP2 from the canalicular
      membrane, whereas down-regulation of MRP2 mRNA is a later event. LPS-induced MRP2
      retrieval from the canalicular membrane is not associated with the retrieval of
      DPPIV, suggestive for selectivity of the process.

PMID- 9922323
TI  - Mechanisms of gallbladder hypomotility in pregnant guinea pigs.
AB  - BACKGROUND & AIMS: Gallbladder muscle contraction becomes impaired during
      pregnancy. This study was designed to investigate the mechanisms of gallbladder
      hypomotility induced by pregnancy in guinea pigs. METHODS: Gallbladder muscle
      cells were obtained by enzymatic digestion. Cell contraction was expressed as
      percent shortening of initial control cell length. RESULTS: Contraction induced
      by cholecystokinin (CCK)-8 or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was
      reduced in muscle cells from pregnant guinea pigs. The response to KCl or D-myo
      inositol 1,4, 5-trisphosphate was not different between controls and pregnant
      animals. These findings suggest that impaired contraction in pregnancy might be
      caused by defective G protein activation. The function and content of G proteins
      were examined by using [35S]GTPgammaS binding and G protein subunit quantitation.
      In female controls, CCK-8 at 1 micromol/L caused increased [35S]GTPgammaS binding
      to Galphai3 but not to Galphaq/11, Galphai1-2, or Galphas. GTPgammaS binding to
      Galphai3 induced by CCK-8 was reduced in gallbladder muscle from pregnant guinea
      pigs. Measurements of basal G proteins showed that the content of Galphai3 was
      significantly lower and the Galphas content was higher in muscles from pregnant
      guinea pigs than in controls. CONCLUSIONS: Pregnancy may cause down-regulation of
      contractile G proteins such as Galphai3 and up-regulation of Galphas that
      mediates relaxation, resulting in impaired gallbladder muscle contraction.

PMID- 9922324
TI  - NF-kappaB/Rel activation in cerulein pancreatitis.
AB  - BACKGROUND & AIMS: Recent evidence suggests that a number of rapid signaling
      cascades are initiated during secretagogue-induced pancreatitis. However, little
      is known about the nuclear events. The aim of this study was to explore
      activation of the transcription factor NF-kappaB/Rel after supramaximal
      stimulation with the cholecystokinin analogue cerulein in the pancreas. METHODS &
      RESULTS: Nuclear appearance of NF-kappaB/Rel-binding activity was detectable 15
      minutes after cerulein injection. The DNA-binding activity consisted of NF
      kappaB1 p50, NF-kappaB2 p52, and RelA p65 as judged by supershift assays and
      Western blot analysis. The onset and termination of NF-kappaB/Rel activation
      correlated with the degradation and reappearance of IkappaBalpha. Cerulein in
      supramaximal but not in physiological doses activated NF-kappaB/Rel in vitro.
      After blocking of NF-kappaB/Rel activation with pyrrolidine dithiocarbamate, the
      degree of morphological alterations was more pronounced than in controls, serum
      amylase and lactate dehydrogenase levels were significantly increased, and
      messenger RNA levels of pancreatitis-associated protein were more strongly
      induced, reflecting a more severe degree of pancreatitis. Similar results were
      obtained when N-acetyl-L-cysteine was used as an inhibitor of NF-kappaB
      activation. CONCLUSIONS: These data show that NF-kappaB/Rel is rapidly activated
      during cerulein pancreatitis. This activation may induce a self-defending genetic
      program before the onset of cellular injury, which might prevent higher degrees
      of damage of pancreatic acinar cells after secretagogue hyperstimulation.

PMID- 9922325
TI  - Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient
      absorption in pancreatic-insufficient dogs.
AB  - BACKGROUND & AIMS: Treatment of human exocrine pancreatic insufficiency is
      suboptimal. This study assessed the effects of bacterial lipase, porcine lipase,
      and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient
      dogs. METHODS: Dogs were given bacterial or porcine lipase and 3 diets: a 48%
      carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low
      fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet
      (66%/18%/16% and 21%/43%/36% calories). RESULTS: With the standard diet,
      coefficient of fat absorption increased dose-dependently with both lipases (P <
      0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of
      bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly
      abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of
      porcine lipase, fat absorption was greater with the high-fat and -protein diet (P
      < 0.05 vs. low-fat and -protein diet). There were no interactions among
      carbohydrate, fat, and protein absorption. CONCLUSIONS: Correcting steatorrhea
      requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat
      and high-protein diets optimize fat absorption with both enzymes. High-fat diets
      with bacterial or porcine lipase should be evaluated in humans with pancreatic
      steatorrhea.

PMID- 9922326
TI  - Contributions of molecular motor enzymes to vesicle-based protein transport in
      gastrointestinal epithelial cells.

PMID- 9922327
TI  - American Gastroenterological Association medical position statement on management
      of oropharyngeal dysphagia.

PMID- 9922328
TI  - AGA technical review on management of oropharyngeal dysphagia.

PMID- 9922329
TI  - Helicobacter pylori, acid, and omeprazole revisited: bacterial eradication and
      rebound hypersecretion.

PMID- 9922330
TI  - p16(INK4): involvement early and often in gastrointestinal malignancies.

PMID- 9922331
TI  - Early events in sepsis-associated cholestasis.

PMID- 9922333
TI  - Glial cells, mucosal integrity, and inflammatory bowel disease.

PMID- 9922332
TI  - NF-kappaB activation in acute pancreatitis: protective, detrimental, or
      inconsequential?

PMID- 9922335
TI  - The curse of the functional dyspeptic: too sensitive a visceral afferent nervous
      system?

PMID- 9922334
TI  - HCV and C282Y: a sinister synergism?

PMID- 9922336
TI  - Mucosal vaccination: "all politics are local".

PMID- 9922337
TI  - Is Helicobacter pylori infection a risk factor for disease severity in rheumatoid
      arthritis?

PMID- 9922338
TI  - Percutaneous ethanol injection therapy of large hepatic tumors: a stereotaxic
      echo-guided approach.

PMID- 9922339
TI  - Mimicry of blood group antigen A by Helicobacter mustelae and H. pylori.

PMID- 9922340
TI  - Training cardiologists in Europe.

PMID- 9922341
TI  - Commotio cordis: sudden death due to chest wall impact in sports.

PMID- 9922342
TI  - Stamps in cardiology. Instituto Nacional de Cardiologia Ignacio Chavez.

PMID- 9922343
TI  - Normal long axis function.

PMID- 9922344
TI  - Neuroendocrine prediction of left ventricular function and heart failure after
      acute myocardial infarction. The Christchurch Cardioendocrine Research Group.
AB  - OBJECTIVE: To determine the relations of plasma levels of brain natriuretic
      peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic
      guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma
      catecholamines to left ventricular function and to prognosis in patients admitted
      with acute myocardial infarction. DESIGN: Plasma hormones and ventricular
      function (radionuclide ventriculography) were measured 1-4 days after myocardial
      infarction in 220 patients admitted to a single coronary care unit. Radionuclide
      scanning was repeated 3-5 months after infarction. Clinical events were recorded
      over a mean period of 14 months. RESULTS: Both early and late left ventricular
      ejection fraction (LVEF) were most closely related to plasma BNP (r = -0.60, n =
      220, p < 0.001; and r = -0.53, n = 192, p < 0.001, respectively), followed by
      ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations
      less than twofold the upper limit of normal (20 pmol/l) had 100% negative
      predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate
      analysis incorporating all the neurohormonal factors, only BNP remained
      independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median
      levels of candidate predictors identified BNP as the most powerful discriminator
      for death (p < 0.0001). No early deaths (within 4 months) occurred in patients
      with plasma BNP concentrations below the group median (27 pmol/l), and over
      follow up only three of 26 deaths occurred in this subgroup. Of all episodes of
      left ventricular failure, 85% occurred in patients with plasma BNP above the
      median (p < 0.001). In multivariate analyses, BNP alone gave additional
      predictive information beyond sex, age, clinical history, LVEF, and plasma
      noradrenaline for both subsequent onset of LVF and death. CONCLUSIONS: Plasma BNP
      measured within 1-4 days of acute myocardial infarction is a powerful independent
      predictor of left ventricular function, heart failure, or death over the
      subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma
      catecholamines.

PMID- 9922345
TI  - Oxygen uptake kinetics during low level exercise in patients with heart failure:
      relation to neurohormones, peak oxygen consumption, and clinical findings.
AB  - OBJECTIVE: To investigate whether oxygen uptake (VO2) kinetics during low
      intensity exercise are related to clinical signs, symptoms, and neurohumoral
      activation independently of peak oxygen consumption in chronic heart failure.
      DESIGN: Comparison of VO2 kinetics with peak VO2, neurohormones, and clinical
      signs of chronic heart failure. SETTING: Tertiary care centre. PATIENTS: 48
      patients with mild to moderate chronic heart failure. INTERVENTIONS: Treadmill
      exercise testing with "breath by breath" gas exchange monitoring. Measurement of
      atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and
      noradrenaline. Assessment of clinical findings by questionnaire. MAIN OUTCOME
      MEASURES: O2 kinetics were defined as O2 deficit (time [rest to steady state] x
      DeltaVO2 -sigmaVO2 [rest to steady state]; normalised to body weight) and mean
      response time of oxygen consumption (MRT; O2 deficit/DeltaVO2). RESULTS: VO2
      kinetics were weakly to moderately correlated to the peak VO2 (O2 deficit, r = 
      0.37, p < 0.05; MRT, r = -0.49, p < 0.001). Natriuretic peptides were more
      closely correlated with MRT (ANF, r = 0.58; BNP, r = 0.53, p < 0.001) than with
      O2 deficit (ANF, r = 0.48, p = 0.001; BNP, r = 0.37, p < 0.01) or peak VO2 (ANF,
      r = -0.40; BNP, r = -0.31, p < 0.05). Noradrenaline was correlated with MRT (r =
      0. 33, p < 0.05) and O2 deficit (r = 0.39, p < 0.01) but not with peak VO2 (r = 
      0.20, NS). Symptoms of chronic heart failure were correlated with all indices of
      oxygen consumption (MRT, r = 0.47, p < 0.01; O2 deficit, r = 0.39, p < 0.01; peak
      VO2, r = -0.48, p < 0. 01). Multivariate analysis showed that the correlation of
      VO2 kinetics with neurohormones and symptoms of chronic heart failure was
      independent of peak VO2 and other variables. CONCLUSIONS: Oxygen kinetics during
      low intensity exercise may provide additional information over peak VO2 in
      patients with chronic heart failure, given the better correlation with
      neurohormones which represent an index of homeostasis of the cardiovascular
      system.

PMID- 9922346
TI  - Angiographic frame counts 90 minutes after streptokinase predict left ventricular
      function at 48 hours following myocardial infarction.
AB  - OBJECTIVE: To assess whether the 90 minute corrected thrombolysis in myocardial
      infarction frame count (CTFC) in the infarct related artery predicts left
      ventricular function at 48 hours in patients with myocardial infarction treated
      with aspirin, streptokinase, and either heparin or Hirulog. DESIGN AND SETTING:
      Analysis of 251 patients with acute myocardial infarction enrolled in the
      international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial,
      who underwent both 90 minute coronary angiography and 48 hour left
      ventriculography. MAIN OUTCOME VARIABLES: The CTFC was determined in the infarct
      related artery 90 minutes after starting intravenous streptokinase (1.5 x 106 U
      over 30 to 60 minutes), and compared with indices of left ventricular function
      assessed by contrast ventriculography at 48 hours. RESULTS: A CTFC of </= 27
      frames (previously reported mean + 2 SD in coronary arteries of patients without
      acute infarction) occurred in 29% of infarct related arteries, and was associated
      with a lower infarct zone mean chord score (-2.06 v -2.54, p = 0.01), a lower
      fraction of chords > 2 SD below normal (37% v 51%, p = 0.005), and trends towards
      higher left ventricular ejection fractions (60.9% v 58.2%, p = 0.11) and lower
      end systolic volumes (50.1 ml v 55.9 ml, p = 0.23). A CTFC of </= 40 at 90
      minutes occurred in 50% of infarct related arteries, and was associated with a
      significantly lower mean chord score (-2.20 v -2.60, p = 0.02), a smaller
      fraction of chords > 2 SD below normal (41% v 52%, p = 0.025), a smaller end
      systolic volume (49.1 ml v 59.3 ml, p = 0.02), and a higher left ventricular
      ejection fraction (60.4% v 56.5%, p = 0.03). CONCLUSIONS: The 90 minute CTFC
      predicts left ventricular function at 48 hours following streptokinase. The CTFC
      associated with better ventricular function may be higher than values determined
      from a non-infarct population.

PMID- 9922348
TI  - Marked variation in the cardiomyopathy associated with Friedreich's ataxia.
AB  - OBJECTIVE: To document the cardiac phenotype associated with Friedreich's ataxia,
      a recessively inherited disorder characterised by spinocerebellar degeneration.
      SETTING: Individuals with Friedreich's ataxia who accepted the invitation to
      participate in the study. HYPOTHESIS: The cardiomyopathy associated with
      Friedreich's ataxia may offer a human model for the study of factors modulating
      cardiac hypertrophy. METHODS: 55 patients (mean (SD) age 30 (9) years) with a
      clinical diagnosis of Friedreich's ataxia were studied by clinical examination,
      electrocardiography, cross sectional and Doppler echocardiography, and analysis
      of the GAA repeat in the first intron of the frataxin gene. RESULTS: A wide
      variety of cardiac morphology was documented. Subjects with normal frataxin
      alleles had no evidence of cardiomyopathy. In homozygous subjects, a relation was
      found between the thickness of the interventricular septum (r = 0.53, p < 0.005),
      left ventricular mass (r = 0.48, p < 0.01), and the number of GAA repeats on the
      smaller allele of the frataxin gene. No relation was shown between the presence
      of electrocardiographic abnormalities (mainly repolarisation changes) and either
      the pattern of ventricular hypertrophy (if present) and degree of neurological
      disability or the length of time since diagnosis. No tendency to ventricular
      thinning or dilatation with age was found. Although ventricular systolic function
      appeared impaired in some cases, Doppler studies of ventricular filling were
      within the normal range for age. CONCLUSIONS: The cardiomyopathy associated with
      Friedreich's ataxia shows a variable phenotype which is not concordant with the
      presence of ECG abnormalities or the neurological features of the condition. As
      the genetic basis for Friedreich's ataxia has been established, further studies
      will help to clarify the molecular mechanisms of the cardiac hypertrophy.

PMID- 9922349
TI  - Clinical usefulness of 123I meta-iodobenzylguanidine imaging in predicting the
      effectiveness of beta blockers for patients with idiopathic dilated
      cardiomyopathy before and soon after treatment.
AB  - OBJECTIVE: To investigate the value of iodine-123 meta-iodobenzylguanidine (MIBG)
      myocardial imaging for defining high risk patients with idiopathic dilated
      cardiomyopathy from among candidates for beta blocker treatment, and for
      predicting functional improvement of the left ventricle in the early stages of
      treatment. METHODS: Echocardiographic indices, neurohormonal measurements, and
      myocardial MIBG distribution were assessed at baseline and after one month and
      three months of treatment in 27 patients with idiopathic dilated cardiomyopathy.
      Patients were classified into two groups, based on whether they reached a daily
      dose of > 20 mg of metoprolol without deterioration of heart failure at three
      months (group A, n = 20) or not (group B, n = 7). RESULTS: There were no
      significant differences in the echocardiographic indices or neurohormonal
      activity at baseline between the two groups, but MIBG uptake was higher, and the
      washout rate lower, in group A than in group B. After one month, though there
      were no significant changes in echocardiographic and neurohormonal variables, the
      heart to mediastinal (H/M) ratio on the delayed image was increased in group A
      but not in group B. In group A, the degree of increase in the H/M ratio on the
      delayed image after one month was also correlated with the degree of reduction in
      plasma concentrations of noradrenaline after three months. CONCLUSIONS: MIBG
      myocardial imaging may be useful for predicting the outcome of beta blocker
      treatment for heart failure patients with idiopathic dilated cardiomyopathy.

PMID- 9922347
TI  - Monocyte expression of tissue factor and adhesion molecules: the link with
      accelerated coronary artery disease in patients with chronic renal failure.
AB  - OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and
      adhesion molecules in patients with chronic renal failure (CRF) and to look for
      any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study
      of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an
      index of thrombin generation, and lipoproteins in patients with CRF and in normal
      control subjects. BACKGROUND: Patients with end stage renal failure have an
      increased risk of coronary artery disease despite advances in therapy. Stimulated
      monocytes are potent activators of blood coagulation through the generation of
      MTF, which was recently implicated in the aetiology of acute coronary ischaemic
      syndromes. METHODS: MTF expression and adhesion molecules were measured in whole
      blood using immunofluorescence of monocytes labelled with anti-tissue factor
      antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in
      plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70
      patients with CRF without documented coronary artery disease (30 patients with
      CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis
      (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls,
      were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3
      (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in
      patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9)
      mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation
      with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein.
      Lp(a) lipoprotein was significantly increased in both dialysis groups compared
      with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte
      adhesion molecule (CD11b) was significantly higher in all three CRF groups than
      in the controls (p = 0.006). CONCLUSION: This study has demonstrated a
      hypercoagulable state in patients with CRF. This was especially pronounced in the
      dialysis patients. These findings provide a possible explanation for the
      increased cardiovascular and cerebrovascular morbidity and mortality in these
      patients.

PMID- 9922351
TI  - Haemolysis following implantation of duct occlusion coils.
AB  - OBJECTIVES: To describe the incidence and management of haemolysis after
      transcatheter coil occlusion of the arterial duct. DESIGN: Prospective clinical
      and echocardiographic follow up of patients who have undergone implantation of
      the Cook detachable duct occlusion coil. SETTING: Tertiary paediatric cardiac
      centre. PATIENTS: Five cases of haemolysis (two girls aged 6 and 11 months; three
      boys aged 6, 17, and 14 months) from a series of 137 duct coil implantations.
      MAIN OUTCOME MEASURES: The occurrence of clinically significant haemolysis after
      implantation of duct occlusion coils and resolution of haematuria after
      completion of duct occlusion. RESULTS: Haemolysis was detected in five of 137
      procedures following implantation of Cook detachable duct coils. Four patients
      became symptomatic 12 hours after the procedure but in one haemolysis was
      detected three months later. Resolution of ongoing haemolysis was achieved within
      48 hours of detection with further coil implantations, but haematuria persisted
      for up to 10 days. In one patient the extensive destruction of erythrocytes
      resulted in acute renal failure requiring peritoneal dialysis. CONCLUSIONS:
      Haemolysis is an important complication after duct coil implantation. It occurred
      in 3.6% of 137 procedures in this series and is most likely to occur in young
      patients with relatively large ducts. Further coil implantation to occlude the
      duct completely is not only successful but technically relatively straightforward
      and should be undertaken early if major complications such as severe anaemia and
      renal failure are to be avoided.

PMID- 9922350
TI  - Assessment of myocardial fatty acid metabolic abnormalities in patients with
      idiopathic dilated cardiomyopathy using 123I BMIPP SPECT: correlation with
      clinicopathological findings and clinical course.
AB  - OBJECTIVE: To determine the clinical and prognostic value of identifying
      metabolic abnormalities of myocardial fatty acid metabolism in idiopathic dilated
      cardiomyopathy using iodine-123 beta-methyl-iodophenyl pentadecanoic acid (123I
      BMIPP). SETTING: Cardiac care division in national hospital. PATIENTS: 32
      consecutive patients with idiopathic dilated cardiomyopathy in whom both 123I
      BMIPP and thallium-201 myocardial single photon emission computed tomography were
      performed. METHODS: The uptake of each tracer was scored visually from 0 (normal)
      to 3 (defect) in 17 segments (eight basal, eight midventricular, and one apical).
      A total score for all 17 segments was compared with clinicopathological
      variables. Prognostic value of mismatches between the two tracers were also
      evaluated. RESULTS: The 123I BMIPP total score was correlated with pulmonary
      capillary wedge pressure (r = 0.68, p < 0.001), left ventricular end diastolic
      pressure (r = 0.65, p < 0.001), percentage fractional shortening at six months'
      follow up (r = -0.58, p = 0. 001), myocyte diameter (r = 0.66, p < 0.001), and
      percentage area of interstitial fibrosis (r = 0.69, p < 0.001) measured by
      morphometry in the biopsy specimens. During a mean (SD) follow up of 20 (11)
      months, deterioration of the New York Heart Association functional class was
      observed in 11 of the 32 patients; four of these died. Segments with a greater
      decrease in 123I BMIPP than thallium-201 uptake (type B mismatching) were often
      observed in patients with deterioration (88/187, 29% v 58/357, 16%; p < 0.001).
      CONCLUSIONS: The extent of the abnormality of myocardial fatty acid metabolism in
      idiopathic dilated cardiomyopathy reflects the severity of haemodynamic
      deterioration and histopathological changes. Type B mismatching is one of the
      important prognostic indicators in idiopathic dilated cardiomyopathy.

PMID- 9922352
TI  - Sustained high pressure double balloon angioplasty of calcified conduits.
AB  - OBJECTIVE: To assess the efficacy of prolonged high pressure angioplasty for
      dilatation of calcified and stenotic cardiac conduits in children. DESIGN: A
      prospective study of consecutive patients presenting with calcified and stenotic
      conduits. SETTING: Two tertiary paediatric cardiology departments. METHODS:
      Sustained (up to five minutes), high pressure (up to 18 atmospheres), double
      balloon angioplasty was performed in six calcified and stenotic cardiac conduits
      (five consecutive patients, three male, two female, age 4 to 17 years). Four
      patients had right ventricle to pulmonary artery (RV-PA) conduits, and one had
      two venous conduits in a Fontan circulation. RESULTS: Marked reductions in right
      ventricle to pulmonary artery gradients, from a median (range) of 48 (40 to 62)
      mm Hg to 11 (5 to 16) mm Hg, and in right ventricle to femoral artery pressure
      ratios, from a median of 0.8 (0.72 to 0.86) to 0.4 (0.33 to 0.44), were achieved
      for all RV-PA conduits. All five patients had sustained clinical improvement at
      follow up (median follow up 12 months) and none has required reintervention or
      surgery. CONCLUSIONS: Prolonged high pressure double balloon angioplasty may have
      a role in prolonging the interval between conduit replacements in a subset of
      patients with complex heart defects.

PMID- 9922354
TI  - Effects of reconstructive surgery for left ventricular anterior aneurysm on
      ventriculoarterial coupling.
AB  - OBJECTIVE: To investigate left ventricular elastance (Emax) and effective
      arterial elastance (Ea) in postinfarction left ventricular aneurysm and evaluate
      their role in left ventricular function improvement after endoventricular
      circular patch plasty (EVCPP). Ventriculoarterial coupling has never been studied
      in these patients. PATIENTS: 22 consecutive patients (49 to 73 years) with left
      ventricular anterior aneurysm. METHODS: Haemodynamic studies were done before and
      two weeks after EVCPP. Ventriculography was performed during atrial pacing (100
      beats/min). Pressure/volume loops were analysed and derived parameters measured.
      Emax was estimated by applying the "single beat" method. Ea was calculated as end
      systolic pressure/stroke volume. RESULTS: Left ventricular volumes and Ea
      decreased after surgery: end diastolic volume index from mean (SD) 155 (53) to
      106 (29); end systolic volume index from 112 (51) to 62 (30) ml/m2 (both p <
      0.0001); Ea from 1.65 (0.70) to 1.39 (0.41) mm Hg/ml (p = 0.04). Ejection
      fraction and Emax increased, without significant changes in stroke volume and
      work. The decrease in Ea was directly correlated with its preoperative value. The
      time interval between left ventricular pressure upstroke and peak systolic
      pressure decreased, from 237 (39) to 191 (41) ms (p < 0.0001), paralleling
      morphological changes in pressure tracings. CONCLUSIONS: After EVCPP,
      ventriculoarterial coupling improves because of the fall in Ea caused by end
      systolic pressure reduction. The improvement is related to aortic pressure
      waveform changes and improved relaxation.

PMID- 9922353
TI  - Middle aortic syndrome treated by stent implantation.
AB  - OBJECTIVES: To determine outcome of stent implantation in patients with middle
      aortic syndrome. DESIGN: Prospective study, case series. SETTING: A tertiary
      paediatric cardiology centre in a children's hospital. PATIENTS: Five patients,
      aged 4 to 17 years (mean 11.4 years), with upper limb hypertension due to middle
      aortic syndrome. INTERVENTION: Stents were implanted in the mid/lower
      thoracic/upper abdominal aorta. MAIN OUTCOME MEASURE: Satisfactory deployment of
      stents and blood pressure control. RESULTS: In all patients, angiocardiography
      showed long segment stenosis in the mid or lower thoracic/upper abdominal aorta.
      The pressure gradient was between 40 and 90 mm Hg (mean 63.2 mm Hg). Seven Palmaz
      stents were implanted. Immediately after implantation, the gradient decreased to
      between 0 and 35 mm Hg (mean 13.6 mm Hg). Angiography showed a satisfactory
      result with widely patent stents in all. In one patient, thrombosis of the stent
      occurred six days after implantation. This was successfully treated with infusion
      of alteplase, further balloon dilatation, and implantation of a second stent
      overlapping the first, both dilated to 10 mm diameter. One patient had elective
      redilatation of the stent six months after implantation, with further reduction
      of the gradient from 35 mm Hg to 10 mm Hg. At the latest follow up between three
      and 20 months (mean 12.2 months) after stent implantation, in four patients blood
      pressure was better controlled with antihypertensive drugs. One patient was
      normotensive without drugs. Computed tomography showed no aneurysm formation in
      the region of the stents. CONCLUSIONS: Stent implantation is a preferable
      alternative to surgery in the treatment of patients with middle aortic syndrome
      and merits further evaluation.

PMID- 9922356
TI  - Probable intracardiac tuberculoma in an HIV positive woman.

PMID- 9922355
TI  - Comparison of long term outcome in patients with or without aortic ring abscess
      treated surgically for aortic valve infective endocarditis.
AB  - OBJECTIVE: To assess the long term prognostic significance of aortic valve ring
      abscess in patients with aortic endocarditis. PATIENTS: A consecutive series of
      75 patients who had surgery for aortic infective endocarditis between 1981 and
      1989; 35 had aortic ring abscesses (group 1) and 40 did not (group 2). Mean age
      did not differ between the two groups. Prosthetic valve endocarditis was present
      in 17% of group 1 and 5% of group 2. Pneumococcal or beta haemolytic
      streptococcal endocarditis was more common in patients with native valve
      endocarditis who had aortic ring abscesses (20% v 5%). DESIGN: Cohort analysis.
      RESULTS: In-hospital mortality (11.4% v 7.5%) and 10 year survival (56% v 66%)
      were not significantly different between groups 1 and 2. In patients with native
      valve endocarditis, 10 year survival was 62% and 66%, respectively for patients
      with or without ring abscess, and 10 year reintervention-free survival was 38% v
      58% (p = 0.11). In these patients, the presence of an intercurrent illness,
      severe congestive heart failure before surgery, and use of valved conduits for
      surgical treatment were predictors of poorer long term survival. At follow up
      residual aortic regurgitation was documented in 72% of patients in group 1 and
      26% in group 2 (p < 0.01). CONCLUSIONS: Aortic valve ring abscess is not an
      independent marker of poor long term outcome in patients with infective
      endocarditis. However, as residual aortic regurgitation appears frequent at
      follow up, specific surgical techniques should be considered in patients with
      paravalvar abscesses.

PMID- 9922357
TI  - Myoarchitecture and connective tissue in hearts with tricuspid atresia.
AB  - OBJECTIVE: To compare the atrial and ventricular myoarchitecture in the normal
      heart and the heart with tricuspid atresia, and to investigate changes in the
      three dimensional arrangement of collagen fibrils. METHODS: Blunt dissection and
      cell maceration with scanning electron microscopy were used to study the
      architecture of the atrial and ventricular musculature and the arrangement of
      collagen fibrils in three specimens with tricuspid atresia and six normal human
      hearts. RESULTS: There were significant modifications in the myoarchitecture of
      the right atrium and the left ventricle, both being noticeably hypertrophied. The
      middle layer of the ventricle in the abnormal hearts was thicker than in the
      normal hearts. The orientation of the superficial layer in the left ventricle in
      hearts with tricuspid atresia was irregular compared with the normal hearts.
      Scanning electron microscopy showed coarser endomysial sheaths and denser
      perimysial septa in hearts with tricuspid atresia than in normal hearts.
      CONCLUSIONS: The overall architecture of the muscle fibres and its connective
      tissue matrix in hearts with tricuspid atresia differed from normal, probably
      reflecting modelling of the myocardium that is inherent to the malformation. This
      is in concordance with clinical observations showing deterioration in pump
      function of the dominant left ventricle from very early in life.

PMID- 9922358
TI  - Imaging of thrombi and assessment of left atrial appendage function: a
      prospective study comparing transthoracic and transoesophageal echocardiography.
AB  - OBJECTIVE: To compare the value of current transthoracic echocardiographic
      systems and transoesophageal echocardiography for assessing left atrial appendage
      function and imaging thrombi. DESIGN: Single blind prospective study. Patients
      were first investigated by transthoracic echocardiography and thereafter by a
      second investigator using transoesophageal echocardiography. The feasibility of
      imaging the left atrial appendage, recording its velocities, and identifying
      thrombi within the appendage were determined by both methods. PATIENTS: 117
      consecutive patients with a stroke or transient neurological deficit. SETTING:
      Tertiary cardiac and neurological care centre. RESULTS: Imaging of the complete
      appendage was feasible in 75% of the patients by transthoracic echocardiography
      and in 95% by transoesophageal echocardiography. Both methods were concordant for
      the detection of thrombi in 10 cases. Transoesophageal echocardiography revealed
      two additional thrombi. In one of these patients, transthoracic echocardiography
      was not feasible and in the other the thrombus had been missed by transthoracic
      examination. In patients with adequate transthoracic echogenicity, the
      specificity and sensitivity of detecting left atrial appendage thrombi were 100%
      and 91%, respectively. Recording of left atrial appendage velocities by
      transthoracic echocardiography was feasible in 69% of cases. None of the patients
      with a velocity > 0.3 m/s had left atrial appendage thrombi. In the one patient
      in whom transthoracic echocardiographic evaluation missed a left atrial appendage
      thrombus, the peak emptying velocity of the left atrial appendage was 0.25 m/s.
      CONCLUSIONS: A new generation echocardiographic system allows for the
      transthoracic detection of left atrial appendage thrombi and accurate
      determination of left atrial appendage function in most patients with a
      neurological deficit.

PMID- 9922360
TI  - Left ventricular wall thickening after surgical correction of anomalous origin of
      left coronary artery from pulmonary artery.

PMID- 9922359
TI  - Cross sectional echocardiographic assessment of the extent of the atrial septum
      relative to the atrioventricular junction in atrioventricular septal defect.
AB  - OBJECTIVE: To study patients with atrioventricular septal defect to determine the
      pathognomonic morphological features of the lesion and the relation between the
      septal structures and the atrioventricular junction. Setting : Tertiary level
      paediatric cardiology centre. METHODS: Cross sectional echocardiograms from 60
      patients were reviewed using qualitative and quantitative analysis. The unifying
      feature was the presence of a common atrioventricular junction. The overall
      dimensions of the septal defect were determined and related to the plane of the
      common junction; the extent of both the atrial and the ventricular septal
      components was then measured according to the site of closure of the bridging
      leaflets. RESULTS: In 48 cases, the common junction was guarded by a common
      valvar orifice, but in 12 cases there were separate right and left valvar
      orifices. Irrespective of the valvar morphology, no significant difference was
      found between the groups in terms of the dimensions of the atrial and ventricular
      septal components. In all patients, the hole permitting shunting at atrial level
      extended below the plane of the atrioventricular junction, with a variable
      position of the leading edge of the atrial septum itself. CONCLUSIONS: The
      atrioventricular junction is a common structure irrespective of valvar
      morphology. In spite of the presence of unequivocal shunting at atrial level, the
      atrial septum is usually a well formed structure, even extending in some below
      the level of the common atrioventricular junction.

PMID- 9922361
TI  - In vitro validation of the luminal measurement of a novel catheter based moulding
      technique.
AB  - OBJECTIVE: To investigate a modified angioplasty balloon catheter, which uses a
      novel balloon polymer to produce luminal moulds. DESIGN: The catheter was tested
      in polyurethane phantoms of diameter 1.5 to 4.0 mm. Inflations were to 1.4
      atmospheres for 20 seconds at 37 degrees C. The moulds were viewed by reinflating
      the balloon to 0. 34 atmospheres and quantified using macrophotography and
      caliper measurement. RESULTS: Evidence of systematic error was found with lumen
      diameters </= 2.0 mm, accuracy being 0.32 to 0.80 mm and precision 0.23 to 0.24
      mm. However, between 2.5 and 4.0 mm the accuracy of measuring luminal diameters
      was 0.01 mm, the precision 0. 06 mm, and the absolute mean error 0.05 mm. The
      results for percentage diameter stenosis were -1.15%, 0.86%, and 1.21%, and for
      lesion length they were 0.20, 0.60, and 0.41 mm, respectively. CONCLUSIONS: The
      prototype catheter shows a high degree of accuracy and precision in phantoms of
      diameter 2.5 to 4.0 mm-the range within which most interventional work is
      performed. Further work on this technique as a method of direct three dimensional
      moulding of the coronary artery lumen is warranted.

PMID- 9922362
TI  - Disparity between studies of the stability of BNP in blood: comparison of
      endogenous and exogenous peptide.

PMID- 9922363
TI  - Giant aneurysm of the left main coronary artery in Takayasu aortitis.
AB  - Takayasu aortitis is a chronic inflammatory vasculitis characterised by stenosis
      or obliteration of large and medium sized arteries. Although coronary arteries
      are affected in approximately 10% of cases, most of the lesions are luminal
      narrowing, and coronary aneurysm formation is extremely rare. A case is described
      of giant aneurysm of the left main coronary artery complicated with Takayasu
      aortitis in a 46 year old Japanese woman who was followed until her death at age
      71. Pronounced intimal proliferation and adventitial fibrous thickening of the
      involved arterial wall usually induce constriction or occlusion at the orifice of
      the main branch of the aorta in Takayasu aortitis. However, systemic
      hypertension, which resulted from renovascular stenoses in this case, is likely
      to have enlarged the vessel lumen before replacement of medial and adventitial
      fibrosis after extensive destruction of medial elastic fibres in the left main
      coronary artery. Moreover, associations such as autoimmune hepatitis, chronic
      thyroiditis, and Sjogren syndrome strongly suggests that Takayasu aortitis may be
      an autoimmune disease.

PMID- 9922364
TI  - A rare case of aortic valve endocarditis caused by Tropheryma whippelii with left
      coronary cusp perforation diagnosed by transoesophageal echocardiography and PCR.

PMID- 9922365
TI  - Intravascular stenting of systemic venous baffle stenosis after corrective
      surgery for double outlet right ventricle with left isomerism.
AB  - A 14 year old girl with double outlet right ventricle, left isomerism, and
      complicated atrial anatomy had undergone corrective surgery with intra-atrial
      rerouting at 5 years of age. Cardiac catheterisation eight years after the
      surgery showed that she had two systemic venous baffle stenoses: between the
      hepatic vein and caval vein, and the caval vein and right atrium. Two Palmaz
      stents were successfully implanted percutaneously through a long sheath and a
      balloon catheter. The stenoses were relieved immediately and her symptoms quickly
      disappeared.

PMID- 9922366
TI  - Chloroquine cardiomyopathy with conduction disorders.
AB  - A 58 year old woman on long term treatment with chloroquine for systemic lupus
      erythematosus presented with cardiac conduction disorders and heart failure with
      hypertrophic cardiomyopathy, which was confirmed by histology to be related to
      chloroquine toxicity. The heart failure improved on stopping chloroquine
      treatment.

PMID- 9922367
TI  - Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and
      mechanisms of action.
AB  - Glucocorticoids are hormone products of the adrenal gland, which have long been
      recognized to have a profound impact on immunologic processes. The communication
      between immune and neuroendocrine systems is, however, bidirectional. The
      endocrine and immune systems share a common "chemical language," with both
      systems possessing ligands and receptors of "classical" hormones and
      immunoregulatory mediators. Studies in the early to mid 1980s demonstrated that
      monocyte-derived or recombinant interleukin-1 (IL-1) causes secretion of hormones
      of the hypothalamic-pituitary-adrenal (HPA) axis, establishing that
      immunoregulators, known as cytokines, play a pivotal role in this bidirectional
      communication between the immune and neuroendocrine systems. The subsequent 10-15
      years have witnessed demonstrations that numerous members of several cytokine
      families increase the secretory activity of the HPA axis. Because this
      neuroendocrine action of cytokines is mediated primarily at the level of the
      central nervous system, studies investigating the mechanisms of HPA activation
      produced by cytokines take on a more broad significance, with findings relevant
      to the more fundamental question of how cytokines signal the brain. This article
      reviews published findings that have documented which cytokines have been shown
      to influence hormone secretion from the HPA axis, determined under what
      physiological/pathophysiological circumstances endogenous cytokines regulate HPA
      axis activity, established the possible sites of cytokine action on HPA axis
      hormone secretion, and identified the potential neuroanatomic and pharmacological
      mechanisms by which cytokines signal the neuroendocrine hypothalamus.

PMID- 9922368
TI  - New perspectives on mechanisms involved in generating epithelial cell polarity.
AB  - Polarized epithelial cells form barriers that separate biological compartments
      and regulate homeostasis by controlling ion and solute transport between those
      compartments. Receptors, ion transporters and channels, signal transduction
      proteins, and cytoskeletal proteins are organized into functionally and
      structurally distinct domains of the cell surface, termed apical and basolateral,
      that face these different compartments. This review is about mechanisms involved
      in the establishment and maintenance of cell polarity. Previous reports and
      reviews have adopted a Golgi-centric view of how epithelial cell polarity is
      established, in which the sorting of apical and basolateral membrane proteins in
      the Golgi complex is a specialized process in polarized cells, and the generation
      of cell surface polarity is a direct consequence of this process. Here, we argue
      that events at the cell surface are fundamental to the generation of cell
      polarity. We propose that the establishment of structural asymmetry in the plasma
      membrane is the first, critical event, and subsequently, this asymmetry is
      reinforced and maintained by delivery of proteins that were constitutively sorted
      in the Golgi. We propose a hierarchy of stages for establishing cell polarity.

PMID- 9922369
TI  - Induction of immunologic tolerance for transplantation.
AB  - In the second half of the 20th century, the transplantation of replacement organs
      and tissues to cure disease has become a clinical reality. Success has been
      achieved as a direct result of progress in understanding the cellular and
      molecular biology of the immune system. This understanding has led to the
      development of immunosuppressive pharmaceuticals that are part of nearly every
      transplantation procedure. All such drugs are toxic to some degree, however, and
      their chronic use, mandatory in transplantation, predisposes the patient to the
      development of infection and cancer. In addition, many of them may have
      deleterious long-term effects on the function of grafts. New immunosuppressive
      agents are constantly under development, but organ transplantation remains a
      therapy that requires patients to choose between the risks of their primary
      illness and its treatment on the one hand, and the risks of life-long systemic
      immunosuppression on the other. Alternatives to immunosuppression include
      modulation of donor grafts to reduce immunogenicity, removal of passenger
      leukocytes, transplantation into immunologically privileged sites like the testis
      or thymus, encapsulation of tissue, and the induction of a state of immunologic
      tolerance. It is the last of these alternatives that has, perhaps, the most
      promise and most generic applicability as a future therapy. Recent reports
      documenting long-term graft survival in the absence of immunosuppression suggest
      that tolerance-based therapies may soon become a clinical reality. Of particular
      interest to our laboratory are transplantation strategies that focus on the
      induction of donor-specific T-cell unresponsiveness. The basic biology,
      protocols, experimental outcomes, and clinical implications of tolerance-based
      transplantation are the focus of this review.

PMID- 9922370
TI  - Mitogen-activated protein kinase: conservation of a three-kinase module from
      yeast to human.
AB  - Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases
      that are activated by diverse stimuli ranging from cytokines, growth factors,
      neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen
      activated protein kinases are expressed in all eukaryotic cells. The basic
      assembly of MAPK pathways is a three-component module conserved from yeast to
      humans. The MAPK module includes three kinases that establish a sequential
      activation pathway comprising a MAPK kinase kinase (MKKK), MAPK kinase (MKK), and
      MAPK. Currently, there have been 14 MKKK, 7 MKK, and 12 MAPK identified in
      mammalian cells. The mammalian MAPK can be subdivided into five families:
      MAPKerk1/2, MAPKp38, MAPKjnk, MAPKerk3/4, and MAPKerk5. Each MAPK family has
      distinct biological functions. In Saccharomyces cerevisiae, there are five MAPK
      pathways involved in mating, cell wall remodelling, nutrient deprivation, and
      responses to stress stimuli such as osmolarity changes. Component members of the
      yeast pathways have conserved counterparts in mammalian cells. The number of
      different MKKK in MAPK modules allows for the diversity of inputs capable of
      activating MAPK pathways. In this review, we define all known MAPK module kinases
      from yeast to humans, what is known about their regulation, defined MAPK
      substrates, and the function of MAPK in cell physiology.

PMID- 9922371
TI  - Mechanisms that regulate the function of the selectins and their ligands.
AB  - Selectins are a family of three cell adhesion molecules (L-, E-, and P-selectin)
      specialized in capturing leukocytes from the bloodstream to the blood vessel
      wall. This initial cell contact is followed by the selectin-mediated rolling of
      leukocytes on the endothelial cell surface. This represents the first step in a
      cascade of molecular interactions that lead to leukocyte extravasation, enabling
      the processes of lymphocyte recirculation and leukocyte migration into inflamed
      tissue. The central importance of the selectins in these processes has been well
      documented in vivo by the use of adhesion-blocking antibodies as well as by
      studies on selectin gene-deficient mice. This review focuses on the molecular
      mechanisms that regulate expression and function(s) of the selectins and their
      ligands. Cell-surface expression of the selectins is regulated by a variety of
      different mechanisms. The selectins bind to carbohydrate structures on
      glycoproteins, glycolipids, and proteoglycans. Glycoproteins are the most likely
      candidates for physiologically relevant ligands. Only a few glycoproteins are
      appropriately glycosylated to allow strong binding to the selectins. Recently,
      more knowledge about the structure and the regulated expression of some of the
      carbohydrates on these ligands necessary for selectin binding has been
      accumulated. For at least one of these ligands, the physiological function is now
      well established. A novel and exciting aspect is the signaling function of the
      selectins and their ligands. Especially in the last two years, convincing data
      have been published supporting the idea that selectins and glycoprotein ligands
      of the selectins participate in the activation of leukocyte integrins.

PMID- 9922372
TI  - Molecular mechanisms of myocardial remodeling.
AB  - "Remodeling" implies changes that result in rearrangement of normally existing
      structures. This review focuses only on permanent modifications in relation to
      clinical dysfunction in cardiac remodeling (CR) secondary to myocardial
      infarction (MI) and/or arterial hypertension and includes a special section on
      the senescent heart, since CR is mainly a disease of the elderly. From a
      biological point of view, CR is determined by 1 ) the general process of
      adaptation which allows both the myocyte and the collagen network to adapt to new
      working conditions; 2) ventricular fibrosis, i.e., increased collagen
      concentration, which is multifactorial and caused by senescence, ischemia,
      various hormones, and/or inflammatory processes; 3) cell death, a parameter
      linked to fibrosis, which is usually due to necrosis and apoptosis and occurs in
      nearly all models of CR. The process of adaptation is associated with various
      changes in genetic expression, including a general activation that causes
      hypertrophy, isogenic shifts which result in the appearance of a slow isomyosin,
      and a new Na+-K+-ATPase with a low affinity for sodium, reactivation of genes
      encoding for atrial natriuretic factor and the renin-angiotensin system, and a
      diminished concentration of sarcoplasmic reticulum Ca2+-ATPase, beta-adrenergic
      receptors, and the potassium channel responsible for transient outward current.
      From a clinical point of view, fibrosis is for the moment a major marker for
      cardiac failure and a crucial determinant of myocardial heterogeneity, increasing
      diastolic stiffness, and the propensity for reentry arrhythmias. In addition,
      systolic dysfunction is facilitated by slowing of the calcium transient and the
      downregulation of the entire adrenergic system. Modifications of intracellular
      calcium movements are the main determinants of the triggered activity and
      automaticity that cause arrhythmias and alterations in relaxation.

PMID- 9922373
TI  - Ten years with CFTR.

PMID- 9922374
TI  - Physiological basis of cystic fibrosis: a historical perspective.
AB  - Physiological Basis of Cystic Fibrosis: A Historical Perspective. Physiol. Rev.
      79, Suppl.: S3-S22, 1999. - Cystic fibrosis made a relatively late entry into
      medical physiology, although references to conditions probably reflecting the
      disease can be traced back well into the Middle Ages. This review begins with the
      origins of recognition of the symptoms of this genetic disease and proceeds to
      briefly review the early period of basic research into its cause. It then
      presents the two apparently distinct faces of cystic fibrosis: 1) as that of a
      mucus abnormality and 2) as that of defects in electrolyte transport. It
      considers principal findings of the organ and cell pathophysiology as well as
      some of the apparent conflicts and enigmas still current in understanding the
      disease process. It is written from the perspective of the author, whose career
      spans back to much of the initial endeavors to explain this fatal mutation.

PMID- 9922375
TI  - Structure and function of the CFTR chloride channel.
AB  - Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79, Suppl.:
      S23-S45, 1999. - The cystic fibrosis transmembrane conductance regulator (CFTR)
      is a unique member of the ABC transporter family that forms a novel Cl- channel.
      It is located predominantly in the apical membrane of epithelia where it mediates
      transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic
      disease cystic fibrosis. The CFTR is composed of five domains: two membrane
      spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory
      (R) domain. Here we review the structure and function of this unique channel,
      with a focus on how the various domains contribute to channel function. The MSDs
      form the channel pore, phosphorylation of the R domain determines channel
      activity, and ATP hydrolysis by the NBDs controls channel gating. Current
      knowledge of CFTR structure and function may help us understand better its
      mechanism of action, its role in electrolyte transport, its dysfunction in cystic
      fibrosis, and its relationship to other ABC transporters.

PMID- 9922376
TI  - CFTR: mechanism of anion conduction.
AB  - CFTR: Mechanism of Anion Conduction. Physiol. Rev. 79, Suppl.: S47-S75, 1999. -
      The purpose of this review is to collect together the results of recent
      investigations of anion conductance by the cystic fibrosis transmembrane
      conductance regulator along with some of the basic background that is a
      prerequisite for developing some physical picture of the conduction process. The
      review begins with an introduction to the concepts of permeability and
      conductance and the Nernst-Planck and rate theory models that are used to
      interpret these parameters. Some of the physical forces that impinge on anion
      conductance are considered in the context of permeability selectivity and anion
      binding to proteins. Probes of the conduction process are considered,
      particularly permeant anions that bind tightly within the pore and block anion
      flow. Finally, structure-function studies are reviewed in the context of some
      predictions for the origin of pore properties.

PMID- 9922377
TI  - Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.
AB  - Control of CTFR Channel Gating by Phosphorylation and Nucleotide Hydrolysis.
      Physiol. Rev. 79, Suppl.: S77-S107, 1999. - The cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- channel is the protein product of the gene
      defective in cystic fibrosis, the most common lethal genetic disease among
      Caucasians. Unlike any other known ion channel, CFTR belongs to the ATP-binding
      cassette superfamily of transporters and, like all other family members, CFTR
      includes two cytoplasmic nucleotide-binding domains (NBDs), both of which bind
      and hydrolyze ATP. It appears that in a single open-close gating cycle, an
      individual CFTR channel hydrolyzes one ATP molecule at the NH2-terminal NBD to
      open the channel, and then binds and hydrolyzes a second ATP molecule at the COOH
      terminal NBD to close the channel. This complex coordinated behavior of the two
      NBDs is orchestrated by multiple protein kinase A-dependent phosphorylation
      events, at least some of which occur within the third large cytoplasmic domain,
      called the regulatory domain. Two or more kinds of protein phosphatases
      selectively dephosphorylate distinct sites. Under appropriately controlled
      conditions of progressive phosphorylation or dephosphorylation, three
      functionally different phosphoforms of a single CFTR channel can be distinguished
      on the basis of channel opening and closing kinetics. Recording single CFTR
      channel currents affords an unprecedented opportunity to reproducibly examine,
      and manipulate, individual ATP hydrolysis cycles in a single molecule, in its
      natural environment, in real time.

PMID- 9922378
TI  - Pharmacology of CFTR chloride channel activity.
AB  - Pharmacology of CFTR Chloride Channel Activity. Physiol. Rev. 79, Suppl.: S109
      S144, 1999. - The pharmacology of cystic fibrosis transmembrane conductance
      regulator (CFTR) is at an early stage of development. Here we attempt to review
      the status of those compounds that modulate the Cl- channel activity of CFTR.
      Three classes of compounds, the sulfonylureas, the disulfonic stilbenes, and the
      arylaminobenzoates, have been shown to directly interact with CFTR to cause
      channel blockade. Kinetic analysis has revealed the sulfonylureas and
      arylaminobenzoates interact with the open state of CFTR to cause blockade.
      Suggestive evidence indicates the disulfonic stilbenes act by a similar mechanism
      but only from the intracellular side of CFTR. Site-directed mutagenesis studies
      indicate the involvement of specific amino acid residues in the proposed
      transmembrane segment 6 for disulfonic stilbene blockade and segments 6 and 12
      for arylaminobenzoate blockade. Unfortunately, these compounds (sulfonylureas,
      disulfonic stilbenes, arylaminobenzoate) also act at a number of other cellular
      sites that can indirectly alter the activity of CFTR or the transepithelial
      secretion of Cl-. The nonspecificity of these compounds has complicated the
      interpretation of results from cellular-based experiments. Compounds that
      increase the activity of CFTR include the alkylxanthines, phosphodiesterase
      inhibitors, phosphatase inhibitors, isoflavones and flavones, benzimidazolones,
      and psoralens. Channel activation can arise from the stimulation of the cAMP
      signal transduction cascade, the inhibition of inactivating enzymes
      (phosphodiesterases, phosphatases), as well as the direct binding to CFTR.
      However, in contrast to the compounds that block CFTR, a detailed understanding
      of how the above compounds increase the activity of CFTR has not yet emerged.

PMID- 9922379
TI  - CFTR is a conductance regulator as well as a chloride channel.
AB  - CFTR Is a Conductance Regulator as well as a Chloride Channel. Physiol. Rev. 79,
      Suppl.: S145-S166, 1999. - Cystic fibrosis transmembrane conductance regulator
      (CFTR) is a member of the ATP-binding cassette (ABC) transporter gene family.
      Although CFTR has the structure of a transporter that transports substrates
      across the membrane in a nonconductive manner, CFTR also has the intrinsic
      ability to conduct Cl- at much higher rates, a function unique to CFTR among this
      family of ABC transporters. Because Cl- transport was shown to be lost in cystic
      fibrosis (CF) epithelia long before the cloning of the CF gene and CFTR, CFTR Cl-
      channel function was considered to be paramount. Another equally valid
      perspective of CFTR, however, derives from its membership in a family of
      transporters that transports a multitude of different substances from
      chemotherapeutic drugs, to amino acids, to glutathione conjugates, to small
      peptides in a nonconductive manner. Moreover, at least two members of this ABC
      transporter family (mdr-1, SUR) can regulate other ion channels in the membrane.
      More simply, ABC transporters can regulate somehow the function of other cellular
      proteins or cellular functions. This review focuses on a plethora of studies
      showing that CFTR also regulates other ion channel proteins. It is the hope of
      the authors that the reader will take with him or her the message that CFTR is a
      conductance regulator as well as a Cl- channel.

PMID- 9922380
TI  - Biosynthesis and degradation of CFTR.
AB  - Biosynthesis and Degradation of CFTR. Physiol. Rev. 79, Suppl.: S167-S173, 1999. 
      Many of the mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene that cause cystic fibrosis interfere with the folding and
      biosynthetic processing of nascent CFTR molecules in the endoplasmic reticulum.
      Mutations in the cytoplasmic nucleotide binding domains, including the common
      allele DeltaF508, decrease the efficiency of CFTR folding, reduce the probability
      of its dissociation from molecular chaperones, and largely prevent its maturation
      through the secretory pathway to the plasma membrane. These mutant CFTR molecules
      are rapidly degraded by cytoplasmic proteasomes by a process that requires
      covalent modification by multiubiquitination. The effects of temperature and
      chemical chaperones on the intracellular processing of mutant CFTR molecules
      suggest that strategies aimed at increasing the folding yield of this protein in
      vivo may eventually lead to the development of novel therapies for cystic
      fibrosis.

PMID- 9922381
TI  - Intracellular CFTR: localization and function.
AB  - Intracellular CFTR: Localization and Function. Physiol. Rev. 79, Suppl.: S175
      S191, 1999. - There is considerable evidence that CFTR can function as a chloride
      selective anion channel. Moreover, this function has been localized to the apical
      membrane of chloride secretory epithelial cells. However, because cystic fibrosis
      transmembrane conductance regulator (CFTR) is an integral membrane protein, it
      will also be present, to some degree, in a variety of other membrane compartments
      (including endoplasmic reticulum, Golgi stacks, endosomes, and lysosomes). An
      incomplete understanding of the molecular mechanisms by which alterations in an
      apical membrane chloride conductance could give rise to the various clinical
      manifestations of cystic fibrosis has prompted the suggestion that CFTR may also
      play a role in the normal function of certain intracellular compartments. A
      variety of intracellular functions have been attributed to CFTR, including
      regulation of membrane vesicle trafficking and fusion, acidification of
      organelles, and transport of small anions. This paper aims to review the evidence
      for localization of CFTR in intracellular organelles and the potential
      physiological consequences of that localization.

PMID- 9922382
TI  - Pathophysiology of gene-targeted mouse models for cystic fibrosis.
AB  - Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis. Physiol. Rev.
      79, Suppl.: S193-S214, 1999. - Mutations in the gene causing the fatal disease
      cystic fibrosis (CF) result in abnormal transport of several ions across a number
      of epithelial tissues. In just 3 years after this gene was cloned, the first CF
      mouse models were generated. The CF mouse models generated to date have provided
      a wealth of information on the pathophysiology of the disease in a variety of
      organs. Heterogeneity of disease in the mouse models is due to the variety of
      gene-targeting strategies used in the generation of the CF mouse models as well
      as the diversity of the murine genetic background. This paper reviews the
      pathophysiology in the tissues and organs (gastrointestinal, airway,
      hepatobiliary, pancreas, reproductive, and salivary tissue) involved in the
      disease in the various CF mouse models. Marked similarities to and differences
      from the human disease have been observed in the various murine models. Some of
      the CF mouse models accurately reflect the ion-transport abnormalities and
      disease phenotype seen in human CF patients, especially in gastrointestinal
      tissue. However, alterations in airway ion transport, which lead to the
      devastating lung disease in CF patients, appear to be largely absent in the CF
      mouse models. Reasons for these unexpected findings are discussed. This paper
      also reviews pharmacotherapeutic and gene therapeutic studies in the various
      mouse models.

PMID- 9922383
TI  - Role of CFTR in airway disease.
AB  - Role of CFTR in Airway Disease. Physiol. Rev. 79, Suppl.: S215-S255, 1999. -
      Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF
      transmembrane conductance regulator (CFTR), which accounts for the cAMP-regulated
      chloride conductance of airway epithelial cells. Lung disease is the chief cause
      of morbidity and mortality in CF patients. This review focuses on mechanisms
      whereby the deletion or impairment of CFTR chloride channel function produces
      lung disease. It examines the major themes of the channel hypothesis of CF, which
      involve impaired regulation of airway surface fluid volume or composition.
      Available evidence indicates that the effect of CFTR deletion alters
      physiological functions of both surface and submucosal gland epithelia. At the
      airway surface, deletion of CFTR causes hyperabsorption of sodium chloride and a
      reduction in the periciliary salt and water content, which impairs mucociliary
      clearance. In submucosal glands, loss of CFTR-mediated salt and water secretion
      compromises the clearance of mucins and a variety of defense substances onto the
      airway surface. Impaired mucociliary clearance, together with CFTR-related
      changes in the airway surface microenvironment, leads to a progressive cycle of
      infection, inflammation, and declining lung function. Here, we provide the
      details of this pathophysiological cascade in the hope that its understanding
      will promote the development of new therapies for CF.

PMID- 9922384
TI  - Identification of peak bone mass QTL in a spontaneously osteoporotic mouse
      strain.
AB  - The whole genome scan for quantitative trait loci (QTLs) specifying peak bone
      mass was performed with the F2 intercrosses of SAMP6, an established murine model
      of senile osteoporosis, exhibiting a significantly lower peak bone mass, and
      SAMP2, exhibiting a higher peak bone mass. Cortical thickness index (CTI), a
      parameter of bone mass of femurs, was measured in 488 F2 progeny at 4 months of
      age, when the animals attained peak bone mass by microphotodensitometry. Genetic
      markers were typed at 90 loci spanning all chromosomes except the Y. By interval
      mapping of 246 male F2 mice, two loci were identified with significant linkage to
      peak bone mass, one on Chromosome (Chr) 11 and another on Chr 13, with a maximum
      lod score of 10.8 (22.2% of the total variance) and 5.8 (10.0%), respectively.
      Another locus on the X Chr was suggestive of a QTL associated oppositely with a
      low peak bone mass to the SAMP2 allele. This association was consistent with the
      distribution of peak bone mass in the F1 and F2. These findings should be useful
      to elucidate the genetics of osteoporosis.

PMID- 9922385
TI  - Mapping and cloning recombinant breakpoints demarcating the hybrid sterility 6
      specific sperm tail assembly defect.
AB  - Variants of the mouse t complex known as t haplotypes (t) express factors that
      perturb sperm differentiation, resulting in the non-Mendelian transmission of t
      from +/t heterozygous males and the sterility of t/t homozygous males. Previous
      studies of mice carrying heterospecific combinations of the t complex have
      revealed a 1-cM candidate locus, Hst6, for the distal-most of these factors,
      Tcd/Tcs2. Males heterozygous for the M. spretus allele of Hst6 and a t haplotype
      (Hst6(s)/t) are sterile, expressing an abnormality in sperm flagellar curvature
      ("curlicue") indistinguishable from one exhibited by sperm from t/t homozygotes.
      Hst6(s)/Hst6(s) males are also sterile; however, sperm produced by these males
      are completely immotile owing to the absence of assembled flagella. Recent
      studies have shown that the complete presentation of "curlicue" derives from
      expression of at least two factors within the locus, Curlicue a (Ccua) proximally
      and Curlicue b (Ccub) distally, with a factor affecting sperm-oolemma
      penetration, Stop1p, mapping between them. In the present report, we have
      examined expression of the Hst6-specific flagellar assembly phenotype in sperm
      from mice homozygous for M. spretus-M. m. domesticus recombinant Chr 17 homologs
      whose breakpoints map within the Hst6 locus. SSLP analysis of these homologs has
      demonstrated that the flagellar assembly defect maps to less than 0.2 cM between
      D17Mit61 and D17Mit135, coincident with Ccua. SSR content analysis of 23 BACs
      mapping to four contigs within the Hst6 locus has resulted in isolation of
      proximal and distal recombinant breakpoints circumscribing the flagellar assembly
      phenotype/Ccua factor. In addition, we have provided increased high-resolution
      mapping of the Stop1p and Ccub factors. These new data enhance our ability to
      isolate and characterize candidates for Tcd/Tcs2.

PMID- 9922386
TI  - Genomic sequence comparison of the human and mouse adenosine deaminase gene
      regions.
AB  - A challenge for mammalian genetics is the recognition of critical regulatory
      regions in primary gene sequence. One approach to this problem is to compare
      sequences from genes exhibiting highly conserved expression patterns in disparate
      organisms. Previous transgenic and transfection analyses defined conserved
      regulatory domains in the mouse and human adenosine deaminase (ADA) genes. We
      have thus attempted to identify regions with comparable similarity levels
      potentially indicative of critical ADA regulatory regions. On the basis of
      aligned regions of the mouse and human ADA gene, using a 24-bp window, we find
      that similarity overall (67.7%) and throughout the noncoding sequences (67.1%) is
      markedly lower than that of the coding regions (81%). This low overall similarity
      facilitated recognition of more highly conserved regions. In addition to the
      highly conserved exons, ten noncoding regions >100 bp in length displayed >70%
      sequence similarity. Most of these contained numerous 24-bp windows with much
      higher levels of similarity. A number of these regions, including the promoter
      and the thymic enhancer, were more similar than several exons. A third block,
      located near the thymic enhancer but just outside of a minimally defined locus
      control region, exhibited stronger similarity than the promoter or thymic
      enhancer. In contrast, only fragmentary similarity was exhibited in a region that
      harbors a strong duodenal enhancer in the human gene. These studies show that
      comparative sequence analysis can be a powerful tool for identifying conserved
      regulatory domains, but that some conserved sequences may not be detected by
      certain functional analyses as transgenic mice.

PMID- 9922387
TI  - Lens epithelial proliferation cataract in segmental trisomy involving mouse
      Chromosomes 4 and 17.
AB  - A dominant induced mutation in the mouse, tightly associated with a reciprocal
      chromosomal translocation between Chrs 4 and 17, causes abnormal head tossing and
      circling behavior (the translocation induced circling mutation, Tim). Affected
      mice develop an unusual anterior subcapsular cataract that appears after birth
      and is progressive. The most likely explanation for the phenotypic observations
      is that the translocation breakpoint disrupted a gene or its regulation. Although
      the Mos protooncogene is located close to the translocation breakpoint and
      transgenic mice that overexpress Mos demonstrate cataracts and circling behavior,
      there were no gross changes in the Mos gene or in its level of expression. The
      morphological changes observed in the lens resemble those seen in some human
      congenital cataract syndromes.

PMID- 9922388
TI  - Genomic structure and chromosomal localization of the mouse gene Punc.
AB  - The mouse gene Punc encodes a member of the immunoglobulin superfamily of cell
      surface proteins. It is highly expressed in the developing embryo in nervous
      system and limb buds. At mid-gestation, however, expression levels of Punc
      decrease sharply. To allow investigation of such a regulatory mechanism, the
      genomic locus encompassing the Punc gene was cloned, characterized, and mapped.
      Fluorescent in situ hybridization was used to determine the chromosomal location
      of the Punc gene of mouse and human. Mouse Punc maps to Chromosome (Chr) 9 in the
      region D-E1, whereas the human PUNC gene is localized to Chr 15 at 15q22.3-23, a
      region known to be syntenic to mouse 9D-E1. The human PUNC gene therefore maps
      close to a genetic locus that is linked to Bardet-Biedl Syndrome, an autosomal
      recessive human disorder. Confirmation for the location of human PUNC was
      obtained through sequence relationships between mouse Punc cDNA, human PUNC cDNA,
      genomic sequence upstream of the murine Punc gene, and human STS markers that had
      been previously mapped on Chr 15. The STS sequence WI-14920 is in fact derived
      from the 3'-untranslated region of the human PUNC gene. WI-14920 had been placed
      at 228cR from the top of the Chr 15 linkage group, which provided positional
      information for the human PUNC gene at high resolution. Thus, this study
      identifies PUNC as the gene corresponding to a previously anonymous marker and
      serves as a basis to investigate its role in genetic disorders.

PMID- 9922389
TI  - Two blood pressure/cardiac mass quantitative trait loci on chromosome 3 in Dahl
      rats.
AB  - Interval mapping was used to identify putative quantitative trait loci (QTL) for
      blood pressure and cardiac mass on Chromosome (Chr) 3 in F1(S x R) x S population
      of 150 rats raised on an 8% NaCl diet. Two genetic markers 95.7 cM apart, D3Wox3
      and D3Mco5 (tightly linked to Edn3), showed "suggestive" linkage to blood
      pressure (LOD = 2.0 and 1.8 respectively). In addition, D3Wox3 showed
      "suggestive" linkage to heart weight (LOD = 2.5), and D3Mco5 showed "suggestive"
      linkage to body weight-adjusted heart weight (LOD = 2.1). Congenic rats
      (designated S.R-Edn3) were constructed by introgressing the R-rat Edn3 allele
      (and flanking loci) into the S strain. On a 2% NaCl diet, S.R-Edn3 rats had lower
      blood pressure (21.4 mm Hg, P = 0. 0005) and heart weight (59 mg, P = 0.0038)
      compared with S rats, confirming the existence of a blood pressure QTL on Chr 3
      near Edn3 even though QTL linkage analysis of blood pressure did not achieve
      stringent statistical criteria for significance. The results of the congenic
      experiment and the large distance between the two putative QTL suggest the
      presence of at least two independent blood pressure/cardiac mass QTL detectable
      on Chr 3 in the Dahl rat model of genetic hypertension.

PMID- 9922390
TI  - Interval mapping of growth in divergent swine cross.
AB  - A genomic scan of 18 swine autosomal chromosomes was constructed with 119
      polymorphic microsatellite (ms) markers to identify quantitative trait loci (QTL)
      for 11 growth traits in the University of Illinois Meishan x Yorkshire Swine
      Resource Family. A significant QTL effect was found for post-weaning average
      daily gain (ADG) between 5.5 and 56 kg of body weight that mapped between markers
      SW373 and SW1301 near the telomere of Chromosome (Chr) 1 q (SSC1). This QTL
      effect had a nominal (pointwise) p-value of 0.000007, a genome wide p-value of
      0.012, and accounted for 26% of the F2 phenotypic variance. The same chromosome
      region also had significant effects on ADG between birth and 56 kg body weight (p
      value =. 000227), and on ADG between 35 and 56 kg (p-value =.00077). These
      observations suggest that a significant QTL for post-weaning growth resides on
      SSC1.

PMID- 9922391
TI  - Genetic variation at the porcine MYF-5 gene locus. Lack Of association with meat
      production traits.
AB  - The number of muscle fibers at birth appears to determine the maximal lean meat
      growth capacity in pigs and in cattle. Development of muscle fibers is regulated
      by the MyoD gene family consisting of MyoD1, myf-5, myf-6, and myogenin. Myf-5 is
      expressed in proliferating myoblasts. Here we report the genomic sequence of the
      porcine myf-5 gene with three microsatellites and two RFLPs located close to the
      coding sequences. Two of the microsatellites are located in the promoter region.
      The allelic distribution differs between breeds and selection lines. In two GY
      selection lines, 1216 pigs of two-generation families were genotyped for the
      HinfI RFLP, which was segregating in the GY breed. The other polymorphic loci are
      physically linked to this RFLP locus, and therefore the results can be
      extrapolated to these loci. Statistical analysis revealed no association with
      birth weight, growth rate, weight at slaughter age, carcass meat weight, and
      backfat thickness. Thus, in this study myf-5 did not explain genetic variation in
      meat (muscle) development in pigs.

PMID- 9922392
TI  - Identification and genetic mapping of bovine chemokine genes expressed in
      epithelial cells.
AB  - RNA fingerprinting by arbitrarily primed (RAP)-PCR was used to identify two
      bovine genes that were differentially expressed in epithelial cells during an
      inflammatory response. RNA fingerprints revealed two differentially amplified
      transcripts when monolayers of Madin-Darby bovine kidney (MDBK) cells were
      stimulated with Escherichia coli O157:H7 lipopolysaccharide (LPS) in combination
      with cycloheximide (CX). Sequence analysis showed that both transcripts encoded
      members of the alpha C-X-C chemokine family; one was interleukin 8 (IL-8), and
      the other was a protein closely related to bovine growth-regulated protein (GRO)
      gamma (89% identical). The latter putative epithelial cell inflammatory protein
      was designated ECIP-1. IL-8 and ECIP-1 genes were placed on the cattle genetic
      map with single-nucleotide polymorphism (SNP) markers amplified from genomic DNA.
      Multi-point linkage analysis indicated that the gene locations were
      indistinguishable from those of serum albumin (ALB) and vitamin D-binding protein
      (GC) on bovine Chromosome (BTA) 6. In humans, ALB and GC are located near IL-8,
      GRO-gamma, and seven other alpha chemokines on Chr 4 (HSA 4q11-4q13), suggesting
      that this gene cluster has been conserved on BTA6. These results provide a
      starting point for characterizing allelic variation in chemokine genes and their
      role in the pathogenesis of bacterial infections in cattle.

PMID- 9922394
TI  - Two SINE families associated with equine microsatellite loci.
AB  - BLAST searches of 61 equine microsatellite sequences revealed two related
      families of retroposons. The first family included seven markers, all of which
      showed significant homology to the Equine Repetitive Element-1 (ERE-1) Short
      Interspersed Nucleotide Element (SINE) sequence. Length of homology ranged from
      76 to 171 bases with identities to the ERE-1 consensus sequence ranging from 71%
      to 83%. The second family referred to as Equine Repetitive Element-2 (ERE-2) has
      a consensus sequence that showed homology to ERE-1 over approximately 60 bases.
      These 60 bases comprised subunit I. Sequence comparisons for the two retroposons
      led to the identification of a subunit II, subunit III, as well as the tRNAser
      subunit. The subunit structure of ERE-1 was tRNAser-I-II. By contrast, the
      subunit structure of ERE-2 was I-III-III. The nine markers related to ERE-2
      showed homology lengths ranging from 84 to 163 bases with identities ranging from
      75% to 99%. In addition to being present in microsatellites, ERE-2 appeared in
      three separate equine genes. It occurred in an intron of DNA-PK, in an
      untranslated region as well as in the promoter of PGHS, and in the coding region
      of PAM. The amino acids corresponding to the ERE-2 sequence in PAM were not
      present in the human or mouse PAM homologs. These amino acids associated with the
      ERE-2 sequence were present on the cytosolic side of the transmembrane domain of
      the PAM enzyme. Microsatellite markers in the ERE-1 and ERE-2 families were found
      throughout the genus equus and also for rhinoceros, indicating that the
      appearance of both retroposons predates the divergence of equids from the other
      perissodactyls. The markers did not amplify in human or bovine DNA. This
      indicated that ERE-1 and ERE-2 are, at least, perissodactyl specific.

PMID- 9922393
TI  - Molecular characterization and chromosomal assignment of the canine protein C
      gene.
AB  - Protein C is a precursor to a serine protease present in the plasma that plays an
      important physiological role in the regulation of blood coagulation. Mutations in
      the human protein C gene have been linked to some cases of Morbus Perthes
      disease, a thrombophilic condition that results in aseptic necrosis of the femur
      head and neck. We have cloned the canine protein C gene to investigate whether
      Morbus Perthes disease in dogs is also caused by mutations within this gene. A
      genomic lambdaFIXII clone was isolated, and 11, 420 bp of DNA sequence were
      determined containing the complete protein C gene (Acc No. AJ001979). As in
      humans, the gene consists of nine exons with the translation start codon located
      in the second exon. The 1.7-kb mRNA contains a 1368-bp open reading frame coding
      for 456 amino acids. With the genomic protein C clone as a probe in a FISH
      experiment, the canine protein C gene was assigned to Chromosome (Chr) 19q21-q22.
      To search for possible mutations, we amplified genomic DNA from one healthy and
      15 clinically and pathohistologically confirmed Morbus Perthes patients. Sequence
      analysis did not reveal any amino acid differences between the affected dogs and
      the normal control. Several nucleotide polymorphisms were detected, which
      however, did not result in an amino acid exchange. From these data we conclude
      that in contrast to human, canine Morbus Perthes disease is most likely not
      caused by mutations within the protein C gene.

PMID- 9922395
TI  - A successful strategy for comparative mapping with human ESTs: 65 new regional
      assignments in the pig.
AB  - Large-scale sequencing of cDNAs from numerous tissues is currently being
      performed within the framework of the Human Genome Project. These expressed
      sequence tags (ESTs) are then mapped on a radiation hybrid panel to produce a
      high-resolution map of human genes. In this report, we estimate the efficiency of
      mapping these ESTs in the pig. A total of 344 human ESTs from Genethon were
      selected for amplification in other species by Zoo-PCR: 186 of these could be
      reproducibly amplified by use of pig DNA and the corresponding human primer
      pairs. One-hundred seven of these were tested on a porcine-rodent somatic cell
      hybrid panel, permitting regional localizations of 65 ESTs with agarose or single
      strand conformation polymorphism analysis gels. The corresponding pig PCR
      products were sequenced: 60 ESTs matched significantly with the expected human
      sequences. Fifty-one of these localizations in the pig are in agreement with the
      comparative mapping data between humans and pigs based on heterologous chromosome
      painting. Seven ESTs that were localized in an unexpected region may indicate new
      chromosomal correspondences. This work significantly increases the number of
      genes mapped on the pig genome and demonstrates that this approach can be
      successfully applied to improve the gene density of mammalian genomic maps in
      chromosomal regions of interest, such as those in which QTL (Quantative Trait
      Loci) have been identified.

PMID- 9922396
TI  - Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4.
AB  - A large number of cDNAs coding for killer cell inhibitory receptors (KIR) and
      immunoglobulin-like transcripts (ILT) have already been described, and some of
      the respective genes are known to map in 19q13.4. To understand the genetic
      relationships of these transcripts, some of which may be alleles from polymorphic
      loci, it is necessary to determine the genomic organization of the region. To do
      so, we performed long-range restriction enzyme mapping of the 19q13.4 region
      along with YAC and PAC contig construction. Eighteen genes could be assigned to a
      chromosomal segment of about 600 kb. Twelve KIR loci are contained within
      approximately 200 kb, bordered by the locus for the Fc receptor for IgA (FCAR) at
      the telomeric side and by a 150-kb cluster containing ILT loci at the centromeric
      side. A further region with a maximal size of 135 kb containing at least one ILT
      gene was identified further centromeric, separated by approximately 50 kb from
      the ILT region near the KIR cluster. The entire KIR/ILT region revealed a
      considerable degree of genetic polymorphism as shown, for example, by different
      restriction maps of two sets of PACs spanning the same region. We suggest the
      designation "Leukocyte Receptor Cluster" (LRC) for this chromosomal segment.

PMID- 9922397
TI  - Genotypic and phenotypic characterization of six new recombinant congenic strains
      derived from NOD/Shi and CBA/J genomes.
AB  - Recombinant Congenic Strains (RCS) are useful for dissecting complex polygenic
      traits. Here, we describe genetic and phenotypic characterization of six new RCS
      generated from outcrosses between NOD/Shi and CBA/LsLt, followed by sib mating of
      first backcross progeny (to CBA) for 20 generations, whereupon genetic and
      phenotypic analysis commenced. Four of the RCS were selected on the basis of
      residual heterozygosity present at F20 in one of the three original RCS. Contrary
      to expectations for RCS developed at first backcross, all derived at least 50% of
      the polymorphic markers typed from the NOD parental strain. Development of
      autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD is a strain-specific
      characteristic. The major genetic component predisposing NOD mice to IDDM, their
      H2(g7) haplotype, was present in all RCS. Nevertheless, the presence of variable
      amounts of CBA genome at non-MHC loci conferred complete resistance in all RCS to
      spontaneous IDDM development, and rendered them strongly resistant to
      cyclophosphamide-induced IDDM. Although the RCS more resemble NOD in regard to
      certain strain-specific characteristics, such as prolificacy, an immunologic
      phenotype that was significantly reduced when compared to both parental strains
      was the number of peripheral CD8(+) T cells. Given the genetic characterization
      presented, these new RCS should prove valuable to investigators interested in
      studying genes controlling differential susceptibilities distinguishing the NOD
      and CBA inbred strain backgrounds.

PMID- 9922398
TI  - Models for prediction and recognition of eukaryotic promoters.

PMID- 9922400
TI  - The imprinted domain in mouse distal Chromosome 7: reagents for mutagenesis and
      sequencing.

PMID- 9922401
TI  - A genetic linkage map of rat Chromosome 15 derived from five F2 crosses.

PMID- 9922399
TI  - Multiplex inheritance of component phenotypes in a murine model of lupus.
AB  - We analyzed the linkage of GN and a wide spectrum of serological phenotypes
      associated with systemic lupus erythematosus in a (NZM2410 x C57BL/6)F2 cross.
      Some phenotypes, such as glomerulonephritis (GN) and anti-chromatin IgG antibody
      production, were more penetrant in females, but others, such as anti-dsDNA
      antibody production, did not show a gender bias. These results suggest that
      gender bias affects only a subset of SLE-component phenotypes, and that NZM2410
      can be used to dissect the genetic basis of this phenomenon. Genome scanning
      linked six chromosomal intervals with the expression of one or more component
      phenotypes. These loci included two Sle loci previously identified in an (NZM2410
      x B6)F1 x NZM2410 backcross, loci identified by others in the NZB/W model. Our
      analysis also suggested two new intervals on chromosomes (Chrs.) 10 and 11.
      Detailed analysis of the segregation of different phenotypes within these
      intervals suggests that they encompass more than one susceptibility locus. This
      clustering has been a common finding in several murine polygenic traits. Each of
      NZM2410 susceptibility loci can be aligned with a specific genetic pathways
      contributing to SLE pathogenesis on the basis of the spectrum of component
      phenotypes expressed.

PMID- 9922403
TI  - Genetic polymorphisms in the leptin gene and their association with fatness in
      four pig breeds.

PMID- 9922402
TI  - A locus responsible for arrest of spermatogenesis is located on rat Chromosome
      12.

PMID- 9922404
TI  - Murine Pkd1 introns 21 and 22 lack the extreme polypyrimidine bias present in
      human PKD1.

PMID- 9922405
TI  - The bicoid-related Pitx gene family in development.

PMID- 9922406
TI  - Decorin, epiphycan, and lumican genes are closely linked on murine Chromosome 10
      and are deleted in lethal steel mutants.

PMID- 9922409
TI  - Emergency department-based HIV screening and counseling: experience with rapid
      and standard serologic testing.
AB  - STUDY OBJECTIVE: We sought to (1) determine whether some emergency departments
      could play an important role in the national strategy of early HIV detection
      through the implementation of a voluntary HIV screening program and (2) describe
      the experience with standard and rapid HIV testing. METHODS: Consenting adults
      were enrolled during 3 distinct phases between 1993 and 1995 for the assessment
      of routine testing only, routine versus rapid testing, and rapid testing only.
      Patients administered the rapid test were given information at the time of the
      visit. We assessed the cost of the program. RESULTS: Of 3,048 patients
      approached, 1,448 (48%) consented, 981 to standard and 467 to rapid testing. Of
      these, 6.4% and 3.2%, respectively, were newly identified as being HIV
      seropositive. More than twice as many new infections were diagnosed among those
      discharged from the ED as among those admitted (55 versus 21). Even among those
      previously tested, 5% proved seropositive. The mean+/-SD time to obtain results
      for the rapid assay performed in the hospital's main laboratory was 107+/-52
      minutes, with 55% leaving the ED before receiving the results. Rapid assays
      performed in the ED satellite laboratory required 48+/-37 minutes, and only 20%
      left before getting the results. Follow-up among HIV-seropositive patients was
      64% for the standard protocol and 73% for the rapid protocol (P >. 20). The
      prearranged HIV clinic intake appointment was kept by 62%. Rapid test sensitivity
      and specificity were 100% and 98.9%, respectively, with 5 initial false-positives
      and no false-negatives. Cost per patient enrolled and counseled was $38. Cost per
      infection detected was $601 for the routine test and $1,124 with the rapid test;
      these prices are competitive with those incurred at other sites. CONCLUSION:
      Emergency department-based HIV testing was well accepted and detected a
      significant number of new HIV infections earlier than might have otherwise been,
      particularly among patients sent home. The rapid test is best performed on-site
      and is very sensitive. Confirmation of initial results is required because of the
      occurrence of occasional false-positive results. With relatively high HIV
      detection and return rates, it is evident that some EDs could play a major role
      in the national strategy of early HIV detection.

PMID- 9922408
TI  - Use of heliox-driven nebulizer therapy in the treatment of acute asthma.
AB  - STUDY OBJECTIVE: To compare the effectiveness of a helium-oxygen mixture with
      that of oxygen alone as an aerosolizing gas for beta-agonist therapy in patients
      with mild to moderate exacerbation of asthma. METHODS: A prospective, single
      blinded study was performed in an urban teaching hospital over a period of 5
      months. A convenience sample of 205 patients with mild to moderate exacerbation
      of asthma were enrolled. The participants were randomly assigned to 1 of 2
      groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10
      L/min of oxygen, 15 minutes apart. The second group received 3 doses of
      albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture
      (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital
      capacity (FVC), and forced expiratory volume in 1 second (FEV1 ) were measured
      before and after each treatment. Only PEFR and FEV1 were used in data analysis.
      RESULTS: Although both the heliox and the oxygen group showed significant
      improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively),
      the difference between the 2 groups was clinically and statistically
      insignificant (P =.56). Similar findings were observed for FEV1. There was no
      difference in rate of admission or rate of complications between the 2 groups.
      CONCLUSION: Despite its ability to decrease the turbulent flow in airways and to
      reach distal pulmonary tissues, heliox had no clinically significant advantage
      over standard therapy in the treatment of mild to moderate asthma. Further large
      scale studies are necessary to determine the clinical efficacy of heliox in this
      setting.

PMID- 9922410
TI  - Antibody titers to hepatitis B surface antigen among vaccinated emergency
      physicians: three years' experience with a wellness booth.
AB  - STUDY OBJECTIVE: To determine antibody titers to hepatitis B surface antigen
      (anti-HBsAg) among previously vaccinated emergency physicians and to assess the
      degree of compliance with Centers for Disease Control and Prevention (CDC)
      postvaccination guidelines. METHODS: A descriptive analysis was performed of anti
      HBsAg titer determinations and vaccination surveys among a self-selected group of
      emergency physicians attending the annual scientific assembly of the American
      College of Emergency Physicians in 1995, 1996, or 1997. RESULTS: Of 943
      participants, titer levels were found to be protective in 768 (81%), borderline
      in 45 (5%), and nonreactive in 130 (14%). A total of 337 participants (36%) had
      not obtained postvaccination titer determinations, as advised by the CDC. More
      than 50% reported an occupational exposure to blood products within the previous
      2 years. CONCLUSION: Despite their high risk for exposure to blood products, many
      previously vaccinated emergency physicians were not in compliance with CDC
      postvaccination guidelines.

PMID- 9922411
TI  - Compliance with universal precautions among emergency department personnel caring
      for trauma patients.
AB  - STUDY OBJECTIVE: Emergency department personnel are at high risk of occupational
      infection with bloodborne pathogens. The objective of this study was to observe
      and analyze the use of barrier precautions among ED personnel caring for trauma
      patients. METHODS: This observational study used videotapes of trauma cases seen
      at an urban Level I trauma center. Study participants were ED and trauma team
      personnel. Trained observers scored breaks in the use of barrier precautions
      during the first 15 minutes of 88 videotaped Level I trauma cases. "Major" breaks
      were scored when ED personnel performed invasive procedures without gloves, mask,
      gown, and adequate eye protection. "Minor" breaks were scored when ED personnel
      were adjacent to a trauma patient (within 1 m) without wearing these items.
      RESULTS: We observed 1 or more major breaks in 33.6% of 304 invasive procedures.
      The most common major break was failure to wear a mask (32.2% of procedures),
      followed by inadequate eyewear (22.2%), no gown (5.6%), and no gloves (3.0%). We
      observed minor breaks during 55.5% of 752 patient encounters. Large and
      statistically significant variations were seen in use rates of barrier
      precautions among different groups of personnel; surgery residents were most
      likely to use precautions, whereas attending surgeons were least likely.
      CONCLUSION: Compliance with universal precautions is poor in this high-risk
      clinical setting. These data provide a baseline for measuring the effectiveness
      of interventions to improve compliance. Videotaped observations are a novel and
      effective tool in this setting.

PMID- 9922412
TI  - Occult pneumonias: empiric chest radiographs in febrile children with
      leukocytosis.
AB  - STUDY OBJECTIVE: We sought to determine the incidence of radiographic findings of
      pneumonia in highly febrile children with leukocytosis and no clinical evidence
      of pneumonia or other major infectious source. METHODS: We conducted a
      prospective cohort study at a large urban pediatric hospital. Clinical practice
      guidelines for the use of chest radiography in febrile children were established
      by the emergency medicine attending staff. All records of emergency department
      patients with leukocytosis (WBC count >/= 20, 000/mm3), triage temperature 39.0
      degreesC or higher, age 5 years or less were reviewed daily for 12 months.
      Physicians completed a questionnaire to note the diagnosis, the presence of
      respiratory symptoms and signs, and the reason for the chest radiograph (if one
      was obtained). Patients were excluded for immunodeficiency, chronic lung disease,
      or major bacterial sources of infection other than pneumonia. Pneumonia was
      defined by an attending radiologist's reading of the radiograph. RESULTS: We
      studied 278 patients. Chest radiographs were obtained in 225 for the following
      reasons: 79 because of respiratory findings suggestive of pneumonia and 146
      because of leukocytosis and no identifiable major source of infection. Fifty
      three patients did not undergo radiography. Pneumonia was found in 32 of 79 (40%;
      95% confidence interval, 20% to 52%) of those with findings suggestive of
      pneumonia and in 38 of 146 (26%; 95% confidence interval, 19% to 34%) of those
      without clinical evidence of pneumonia. If patients who did not have a radiograph
      are assumed to not have pneumonia, the minimum estimate of occult pneumonia was
      38 of 199 patients (19%; 95% confidence interval, 14% to 25%). CONCLUSION:
      Empiric chest radiographs in highly febrile children with leukocytosis and no
      findings of pneumonia frequently reveal occult pneumonias. Chest radiography
      should be considered a routine diagnostic test in children with a temperature of
      39 degreesC or greater and WBC count of 20,000/mm3 or greater without an
      alternative major source of infection.

PMID- 9922413
TI  - A prospective, population-based study of the demographics, epidemiology,
      management, and outcome of out-of-hospital pediatric cardiopulmonary arrest.
AB  - STUDY OBJECTIVES: To perform a population-based study addressing the demography,
      epidemiology, management, and outcome of out-of-hospital pediatric
      cardiopulmonary arrest (PCPA). METHODS: Prospective, population-based study of
      all children (17 years of age or younger) in a large urban municipality who were
      treated by EMS personnel for apneic, pulseless conditions. Data were collected
      prospectively for 3(1/2) years using a comprehensive data collection tool and on
      line computerized database. Each child received standard pediatric advanced
      cardiac life support. RESULTS: During the 3(1/2)-year period, 300 children
      presented with PCPA (annual incidence of 19. 7/100,000 at risk). Of these, 60%
      (n=181) were male (P =.0003), and 54% (n=161) were patients 12 months of age or
      younger (152,500 at risk). Compared with the population at risk (32% black
      patients, 36% Hispanic patients, 26% white patients), a disproportionate number
      of arrests occurred in black children (51.6% versus 26.6% in Hispanics, and 17%
      in white children; P <.0001). Over 60% of all cases (n=181) occurred in the home
      with family members present, and yet those family members initiated basic CPR in
      only 31 (17%) of such cases. Only 33 (11%) of the total 300 PCPA cases had a
      return of spontaneous circulation, and 5 of the 6 discharged survivors had
      significant neurologic sequelae. Only 1 factor, endotracheal intubation, was
      correlated positively with return of spontaneous circulation (P =.032).
      CONCLUSION: This population-based study underscores the need to investigate new
      therapeutic interventions for PCPA, as well as innovative strategies for
      improving the frequency of basic CPR for children.

PMID- 9922414
TI  - Adenosine and pediatric supraventricular tachycardia in the emergency department:
      multicenter study and review.
AB  - STUDY OBJECTIVE: To determine the frequency of successful cardioversion and the
      adverse effects of adenosine treatment in pediatric emergency department patients
      with supraventricular tachycardia (SVT). METHODS: This was a multicenter
      descriptive study with both prospective (convenience sample) and retrospective
      (chart review) patient entry. The setting was 7 urban pediatric EDs with a yearly
      census range of 22,000 to 70,000 visits. Pediatric patients 18 years of age and
      younger who received intravenous adenosine for presumed SVT were eligible.
      RESULTS: Six investigators from 7 pediatric EDs entered 82 patients with 98
      presumed SVT episodes (52 prospective and 46 retrospective) into the study.
      Twenty-five episodes occurred in children younger than 1 year of age. Eight
      patients had congenital heart disease, 59 had a history of SVT, 43 were taking
      cardiac medications (digoxin in 27), 13 had a history of asthma, and 25 presented
      in compensated cardiogenic shock. A total of 193 intravenous doses of adenosine
      were administered; doses were classified as low (<.1 mg/kg [n=18]), medium (.1 to
      <.2 mg/kg [n=116]), or high (>/=.2 mg/kg [n=59]). The dose range was.03 to.5
      mg/kg, and only 2 doses were higher than.3 mg/kg. A total of 95 patient-events
      were determined to be SVT, all but 5 of which were atrioventricular (AV) node
      dependent; 3 events were ventricular tachycardia. The overall cardioversion
      success rate of adenosine was 72% (71/98), and that for AV node-dependent SVT was
      79% (71/90). Cardioversion was successful for 4 patient-events at a low dose, 44
      at a medium dose, and 23 at a high dose of adenosine. Adverse effects occurred in
      22 patients, and no patient had bronchospasm or hemodynamically significant
      arrhythmia. CONCLUSION: Intravenous administration of adenosine led to successful
      cardioversion in 72% of pediatric ED patient-events that were presumed to be SVT.
      A dose range of.1 to.3 mg/kg was found to be most effective. Adenosine was not
      associated with significant adverse effects.

PMID- 9922415
TI  - Car surfing: an uncommon cause of traumatic injury.
AB  - Car surfing is an infrequent cause of traumatic injuries treated by emergency
      physicians. This very dangerous activity can result in serious injury or death.
      We report 5 cases of injuries caused by car surfing seen at our hospital during
      1996 and 1997. All involved head injuries after a fall from a moving motor
      vehicle. There were 3 male and 2 female patients, and 3 cases were fatal. Health
      care providers should be aware of this type of injury and support efforts to
      prevent it.

PMID- 9922416
TI  - Pediatric cardiopulmonary resuscitation: a collective review.
AB  - Little information is available about the effects of CPR in children, although it
      is known that the outcomes are dismal. Examples of unanswered questions include
      which advanced life support (ALS) procedures should be performed out-of-hospital,
      whether high-dose epinephrine improves survival, and the true prevalence of
      ventricular fibrillation as a presenting rhythm. Children differ from adults as
      to the cause and pathophysiology of cardiopulmonary arrest, but prehospital EMS
      and hospital resuscitation teams were initially designed for the care of adults.
      Because pediatric cardiopulmonary arrest is rare, prospective data are difficult
      to gather, and there are few large published studies. The purpose of this
      collective review was to review the current body of knowledge regarding survival
      rates and outcomes in pediatric CPR and, based on this review, to outline a
      course for future research.

PMID- 9922417
TI  - Priorities for research in emergency medical services for children: results of a
      consensus conference.
AB  - STUDY OBJECTIVE: To arrive at a consensus on the priorities for future research
      in emergency medical services for children. METHODS: A consensus group was
      convened using the Rand-UCLA Consensus Process. The group took part in a 3-phase
      process. Round 1 involved reviewing a compendium of relevant research articles
      and answering a mailed questionnaire. Panel members were asked to prioritize
      topics on the basis of the 1993 Institute of Medicine Report on Emergency Medical
      Services for Children. Participants were asked to rate each topic based on the
      significance of the research, and whether the topic would (1) improve general
      knowledge, (2) change behavior, (3) improve health, (4) decrease the cost of
      care, or (5) change public policy. A 4-point Likert scale was used. Participants
      were also asked if the research would require a multicenter study and if the
      research were feasible. Round 2 of the study involved a meeting of the panel,
      where the results of Round 1 were discussed and the topics were reprioritized.
      The topics were given a rank order and a final ranking was done in Round 3.
      RESULTS: The panel considered a list of 32 topics; these were combined and
      reworded to give them more precise meaning. Several new topics were also added.
      Fifteen topics were given a rank order and placed within the 7 broad categories
      of the Institute of Medicine report. Clinical aspects of emergency care, systems
      organization, configuration, and operation and injury prevention were given high
      priority rankings. The first 5 topics were very close in point-rank order.
      CONCLUSION: The panel was able to develop a list of important topics for future
      research in emergency medical services for children that can be used by
      foundations, governmental agencies, and others in setting a research agenda for
      such services.

PMID- 9922419
TI  - Pediatric resuscitation and emergency medical services.

PMID- 9922418
TI  - Evaluation styles for well-appearing febrile children: are you a "risk-minimizer"
      or a "test-minimizer"?

PMID- 9922420
TI  - Acting without asking: an ethical analysis of the Food and Drug Administration
      waiver of informed consent for emergency research.
AB  - This article summarizes the current requirements for a waiver of informed consent
      for emergency research and analyzes ethical issues that are involved. Researchers
      who intend to apply for a waiver of informed consent for emergency research must
      understand that they are asking for the major protector of human subjects, the
      informed consent process, to be removed. In its absence, other protections are
      required. These include communication with the community, family members, and
      others close to the patient. It is unlikely that even these additional
      protections can equal that afforded by an adequate consent process. With this
      understanding, investigators' actions must be in accordance with the highest
      ethical standards. It is therefore necessary for investigators to know the
      ethical implications of conducting controlled research without the subjects'
      consent.

PMID- 9922421
TI  - Initial experience using the Food and Drug administration guidelines for
      emergency research without consent.
AB  - Beginning November 6, 1996, Food and Drug Administration regulation 21 CFR 50.24
      has allowed research without consent in limited circumstances while requiring
      additional patient protection in the form of community consultation and
      disclosure. We report our experience in complying with these regulations in
      Multicenter Vest CPR protocol, the first investigational device study done under
      this new ruling. We found uncertainty in inter-pretation of the requirements for
      community consultation. The acceptance of research without consent varied among
      the parties exposed to this protocol, but neither physicians nor the lay public
      expressed major reservations. The consultation process was time-consuming,
      demanding, and relatively costly. Further clarification of the community
      consultation standard and additional dialogue on this important topic will help
      to foster additional research in cardiopulmonary resuscitation.

PMID- 9922422
TI  - Splenic crisis at high altitude in 2 white men with sickle cell trait.
AB  - This article describes 2 white male patients with probable splenic crisis caused
      by sickle cell trait after travel from sea level to a moderately high altitude.
      Both did well with return to lower altitude and conservative treatment. Although
      rare, this entity should be considered in patients presenting to the emergency
      department with left-sided chest or abdominal pain after travel to moderate or
      high altitude.

PMID- 9922423
TI  - The intubating laryngeal mask: use of a new ventilating-intubating device in the
      emergency department.
AB  - The intubating laryngeal mask airway (ILM) was introduced in 1997 as a
      modification of the classic laryngeal mask airway. In addition to serving as an
      elective or emergency ventilating device, it is designed to allow blind
      intubation. We report 3 cases of airway management in the emergency department of
      Yale-New Haven Hospital where the ILM was used to establish ventilation and
      intubation in patients in whom direct laryngoscopy had failed. The 3 cases are
      representative of situations commonly seen in the ED: the obtunded and apneic
      ("crash airway") patient, failed rapid sequence intubation, and the recognized
      difficult airway/awake intubation. In all 3 cases, a clear airway was established
      on initial placement of the ILM, and intubation was achieved on the first attempt
      at blind advancement of the endotracheal tube. Although the ILM may be an
      important addition to the armamentarium of the emergency physician, proficiency
      in its use requires practice under controlled conditions. We suggest that the
      emergency physician seek out elective practice in either a teaching workshop or
      hospital operating theater.

PMID- 9922424
TI  - Marginal gap of crowns made with a phosphate-bonded investment and accelerated
      casting method.
AB  - STATEMENT OF PROBLEM: Numerous materials and methods have been used for complete
      crown fabrication. Conventional investing and casting procedures for phosphate
      bonded investments require a 2- to 4-hour process before completion. Accelerated
      laboratory techniques have been used, but may not result in castings with equal
      marginal accuracy. PURPOSE: This study measured the marginal gap and determined
      the clinical acceptability of single castings invested in a phosphate-bonded
      investment with the use of conventional and accelerated methods. MATERIAL AND
      METHODS: Forty-four individual stone casts were poured from impressions made from
      a master die. Conventional and accelerated methods of investing and casting were
      followed in the fabrication of 44 single-unit castings. Twenty-two casts were
      used in each of the 2 groups. Each casting and its respective stone die were
      examined with a microscope at 4 predetermined sites. Perpendicular and 25-degree
      tilted measurements of marginal gap were documented for each. Evidence of
      marginal gap was then evaluated by t test. RESULTS: Measurements recorded on the
      perpendicular and on a 25-degree tilt showed no statistically significant
      difference between conventional and accelerated groups. All gap measurements
      except one were within the range of clinical acceptability. The measurements
      revealed that conventional and accelerated perpendicular gap means were 13.2 and
      13.6 microm, respectively, and the average tilted gap means were 31.6 and 32.2
      microm, respectively. CONCLUSIONS: A phosphate-bonded investment (Ceramigold)
      selected for an accelerated casting technique produced single castings within 30
      minutes with marginal gaps comparable to those found that used conventional
      methods.

PMID- 9922425
TI  - Current status of luting agents for fixed prosthodontics.
AB  - STATEMENT OF THE PROBLEM: The long-term clinical outcome of fixed prosthodontic
      treatment depends, in part, on the use of adhesives that can provide an
      impervious seal between the restoration and the tooth. There are several types of
      available luting agents, each possessing unique properties and handling
      characteristics. No one product is ideal for every type of restoration. PURPOSE:
      The purpose of this article is to review available dental luting agents, discuss
      improvements and drawbacks in newly formulated adhesives, and present the
      indications for their use. RESULTS: Each cement type is physically and chemically
      unique. A single adhesive will not suffice in modern day clinical practice.

PMID- 9922426
TI  - Effect of tooth surface roughness on marginal seating and retention of complete
      metal crowns.
AB  - STATEMENT OF PROBLEM: Retention and marginal adaptation factors have major
      influence on the failure of cemented complete veneer crowns. PURPOSE: This study
      investigated the effect of axial surface roughness on the marginal seating and
      retention of silver-palladium crowns luted with zinc phosphate, glass ionomer,
      and resin cements. MATERIAL AND METHODS: Coarse and fine diamond stones were used
      to create various surface roughnesses of premolars. A milling machine was used to
      control the height and angle of the axial walls of tooth preparations. Ten cast
      metal crowns in 6 subgroups were luted with 3 cements (Phosphacap, Fuji Cap I,
      and Panavia 21). Marginal seating was recorded with a Digimatic indicator.
      Retention was determined by measuring the tensile force required to remove a
      metal crown with a Lloyd testing machine. RESULTS: Two-way analysis of variance
      revealed statistically significant differences (P <.001) in retention for both
      luting cements and surface roughness. No significant difference was recorded for
      marginal seating relative to roughness (P =.860) and interaction effects (P
      =.204). Tukey-HSD tests revealed substantial differences in retention among
      Phosphacap, Fuji Cap I, and Panavia 21 cements. Significant differences were not
      confirmed in marginal seating between Fuji Cap I and Phosphacap cements with
      coarse diamonds, and Phosphacap and Panavia 21 cements with fine diamonds.
      CONCLUSIONS: The best retention for complete metal crown was demonstrated for
      tooth preparations ground with coarse diamonds and cemented with Panavia 21
      cement. Differences in axial surface roughness had no effect on the marginal
      seating of the complete metal crowns.

PMID- 9922427
TI  - Ischemic osteonecrosis under fixed partial denture pontics: radiographicand
      microscopic features in 38 patients with chronic pain.
AB  - STATEMENT OF PROBLEM: Previous studies have identified focal areas of alveolar
      tenderness, elevated mucosal temperature, radiographic abnormality, and increased
      radioisotope uptake or "hot spots" within the quadrant of pain in most patients
      with chronic, idiopathic facial pain (phantom pain, atypical facial neuralgia,
      and atypical facial pain). PURPOSE: This retrospective investigation
      radiographically and microscopically evaluated intramedullary bone in a certain
      subset of patients with histories of endodontics, extraction, and fixed partial
      denture placement in an area of "idiopathic" pain. MATERIAL AND METHODS: Patients
      from 12 of the United States were identified through tissue samples, histories,
      and radiographs submitted to a national biopsy service. Imaging tests,
      coagulation tests, and microscopic features were reviewed. Of 38 consecutive
      idiopathic facial pain patients, 32 were women. RESULTS: Approximately 90% of
      subpontic bone demonstrated either ischemic osteonecrosis (68%), chronic
      osteomyelitis (21%), or a combination (11%). More than 84% of the patients had
      abnormal radiographic changes in subpontic bone, and 5 of 9 (56%) patients who
      underwent radioisotope bone scan revealed hot spots in the region. Of the 14
      patients who had laboratory testing for coagulation disorders, 71% were positive
      for thrombophilia, hypofibrinolysis, or both (normal: 2% to 7%). Ten pain-free
      patients with abnormal subpontic bone on radiographs were also reviewed.
      CONCLUSIONS: Intraosseous ischemia and chronic inflammation were suggested as a
      pathoetiologic mechanism for at least some patients with atypical facial pain.
      These conditions were also offered as an explanation for poor healing of
      extraction sockets and positive radioisotope scans.

PMID- 9922428
TI  - Assessment of cold welding properties of the internal conical interface of two
      commercially available implant systems.
AB  - STATEMENT OF PROBLEM: The cone-screw abutment has been shown to diminish
      micromovement by reducing the burden of component loosening and fracture.
      However, anecdotal concern for cold welding of cone-screw joints in implant
      design has been identified as a potential source for lack of retrievability.
      PURPOSE: This comparative study evaluated the loosening torque, as a percentage
      of tightening torque, for the ITI Straumann and Astra Tech (3.5 and 4.0 mm
      diameters) implant systems, which use an 8-degree and 11-degree internal cone,
      respectively. MATERIAL AND METHODS: Implants and abutments from each system were
      mounted in a torque device, and a range of tightening torques was applied.
      Loosening torques were then measured, and the influence of conus angle,
      interfacial surface area, saliva contamination, and time delay to loosening were
      all assessed. RESULTS: The loosening torque only exceeded tightening torque at
      the highest levels, just before component failure, when plastic deformation was
      expected. For all clinically relevant levels of torque, both in a dry environment
      and with components bathed in artificial saliva at 37 degrees C, loosening torque
      was always seen to be 80% to 90% of tightening torque, demonstrating that cold
      welding does not occur. There was a high correlation between loosening and
      tightening torque for all systems tested, but no statistical difference when
      comparing wet versus dry or comparing individual data for each system.
      CONCLUSIONS: It can be concluded that for clinically relevant levels of
      tightening torque, no problems are anticipated with respect to retrievability.

PMID- 9922430
TI  - Position paper regarding diagnosis, management, and treatment of
      temporomandibular disorders. The American Equilibration Society.
AB  - The following position paper regarding diagnosis, management, and treatment of
      temporomandibular disorders (TMD) was authored by Dr Peter Dawson on behalf of
      the American Equilibration Society for presentation to the National Institutes of
      Health, Technology Conference on Management of Temporomandibular Disorders, given
      April 29 through May 1, 1996, in Bethesda, Md.

PMID- 9922429
TI  - Modeling of jaw biomechanics in the reconstructed mandibulectomy patient.
AB  - STATEMENT OF PROBLEM: Biomechanics of occlusal force and indirect calculation of
      temporomandibular joint loading in patients after surgery for head and neck
      cancer is poorly understood. PURPOSE: This study compared occlusal force values
      of 6 mandibulectomy subjects with reconstructed mandibles to 6 noncancer subjects
      with intact mandibles and reports occlusal force predictions from a developed
      computer model simulation of both a mandibulectomy subject with a reconstructed
      mandible and noncancer subject with an intact mandible. MATERIAL AND METHODS:
      Maximum occlusal force was recorded at the first molar and incisal edge in 6
      mandibulectomy subjects who had bony reconstruction of the mandible and 6
      noncancer subjects with an intact mandible. Clinical data were then qualitatively
      compared with occlusal force values generated from an existing computer model
      simulating an average adult, and a developed model simulating an average
      mandibulectomy subject who had bony reconstruction of the mandible. The
      biomechanical parameters modeled also included an estimation of joint force
      magnitude and direction when biting with maximal force on the first molar.
      RESULTS: Clinical data revealed no significant differences in occlusal force
      between the 6 mandibulectomy subjects with bony reconstruction of the mandible
      and 6 noncancer subjects with an intact mandible; however, average molar and
      incisal occlusal force values were 22% and 32% less in mandibulectomy subjects
      with bony reconstruction. Computer simulations of a reconstructed mandibulectomy
      subject predicted that reconstructed subjects would have 45% less molar occlusal
      force, 50% less incisal occlusal force, and a higher joint/tooth force ratio
      compared with a simulated noncancer patient with an intact mandible. CONCLUSIONS:
      There were no significant differences in first molar or incisal occlusal force
      between reconstructed mandibulectomy subjects and noncancer subjects with intact
      mandibles. Trends calculated from computer simulations were consistent with
      clinical findings.

PMID- 9922431
TI  - Comparison of chin and jaw movements during gum chewing.
AB  - STATEMENT OF PROBLEM: Knowledge of mastication is based on studies that use jaw
      tracking equipment in nonroutine settings. Ethologists would argue that such data
      probably does not reflect routine masticatory function. If jaw movements could be
      tracked noninvasively, then the hypothesis that jaw tracking equipment and
      nonroutine settings alter mastication could be investigated. PURPOSE: This study
      quantitatively evaluated the relationship between chin and jaw movements during a
      gum-chewing task. MATERIAL AND METHODS: Masticatory chin and jaw movements of 50
      subjects were tracked in the x-, y-, and z-axes for 15 seconds, which resulted in
      approximately 15 chewing cycles obtained per subject. For each chewing cycle,
      magnitude and timing of displacement, velocity, and acceleration extrema in each
      axis were computed for both jaw and chin movement data. Extrema means were
      calculated for each 15-second trial. The respective means representing chin
      versus jaw movements were compared with linear regression and correlation
      analyses. RESULTS: All mean extrema were significantly correlated (r range 0. 30
      0.99; P <.05). Magnitude correlations were larger than timing correlations for
      acceleration extrema. In contrast, magnitude correlations were smaller than
      timing correlations for displacement extrema. The highest correlation occurred
      for chewing rate. CONCLUSIONS: Chin and jaw movements were correlated during
      chewing; however, only chewing rate was highly predictable from chin movement
      data.

PMID- 9922432
TI  - The influence of mandibular movements on joint sounds in patients with
      temporomandibular disorders.
AB  - STATEMENT OF PROBLEM: There are discrepancies among researchers concerning the
      reliability and use of temporomandibular joint sounds. PURPOSE: This study
      examined the reliability of mandibular movements and sounds and determined the
      correlation between movements and sounds. MATERIAL AND METHODS: The mandibular
      movements of 35 subjects diagnosed with temporomandibular disorders were recorded
      with 2 CCD cameras, and sounds were recorded bilaterally with Panasonic electret
      condenser microphones in the ear canal. Subjects performed 3 movements, each
      repeated 5 times. RESULTS: Reliability of maximum movements across the 5 trials
      was good to excellent, with Intraclass Correlation Coefficients (ICC) between
      0.76 and 0.91 for all movements except protrusion. Temporomandibular sound event
      counts were reliable for most movements, including vertical opening, protrusion,
      and right and left laterotrusion (ICCs between 0.41 and 0.81). Most subjects
      produced sound events either in 100% or in none of the trials. Reliability for
      sound events was better during protrusion (ICCs between 0.56 and 0.81) than
      vertical opening (ICCs 0.41 to 0.64). Subjects with sound events during vertical
      opening (followed by closing) were significantly more likely to have sound events
      during protrusion (followed immediately by vertical opening and closing) (P
      <.01). CONCLUSION: Temporomandibular sound events are generally reliable and
      warrant study regarding their use in classifying and diagnosing patients with
      temporomandibular disorders. Condylar translation, which occurs during both
      vertical opening and protrusion, appears to have a strong influence on the
      production of temporomandibular sound events.

PMID- 9922433
TI  - Elastic retracted oral appliance to treat sleep apnea in mentally impaired
      patients and patients with neuromuscular disabilities.
AB  - STATEMENT OF PROBLEM: Various oral appliances have been successfully used in the
      treatment of sleep apnea. However, it is difficult for mentally impaired patients
      and patients with neuromuscular disabilities to insert and remove the appliance
      and to maintain it intraorally through the night. PURPOSE: This study described
      the fabrication of an elastic retracted-type oral appliance to treat sleep apnea
      in mentally impaired patients and patients with neuromuscular disabilities and to
      evaluate its efficiency. MATERIAL AND METHODS: Five patients, 3 with cerebral
      palsy and 2 with Down's syndrome, with sleep apnea were included in this study.
      Maxillary and mandibular splints were molded individually on casts by using
      copolyester foils. The splints were retracted forward by elastics, attached to
      wire hooks in the maxillary and mandibular incisal areas. The effect of the
      appliance was examined polysomnographically. RESULTS: The apnea index was
      decreased significantly (P <.03) by the appliance. The appliance was easily
      inserted and removed, and the elastic force and mandibular position could be
      adjusted. The appliance, as used in this study, allowed free mandibular movement
      and maintained its correct position during sleep despite involuntary or voluntary
      mandibular movements. CONCLUSIONS: The oral appliance was useful as an
      alternative to relieve the sleep apnea of patients with mental deficiencies and
      neuromuscular disabilities.

PMID- 9922434
TI  - Disinfection of denture base acrylic resin.
AB  - STATEMENT OF PROBLEM: During repair or adjustments of acrylic resin removable
      complete and partial dentures, particles of the acrylic resin from the interior
      of the prosthesis may expose dental personnel to microbial health hazards if the
      prosthesis has not been thoroughly disinfected. PURPOSE: This study investigates
      the efficacy of a commercially prepared microbial disinfectant (Alcide) on the
      external and internal surfaces of acrylic resins. MATERIAL AND METHODS: Four
      groups of acrylic resin were incubated in an experimental model to simulate the
      oral environment over time. Specimens were treated in 2 groups, disinfected and
      not disinfected, and then further grouped by breaking and not breaking. Analysis
      was performed with microbial colony counts, SEM, and statistical analyses.
      RESULTS: Viable microorganisms still remain on the internal and external surfaces
      of treated resins. CONCLUSION: Chlorine dioxide reduces, but does not eliminate,
      viable microorganisms on these dental prostheses.

PMID- 9922435
TI  - Microwave disinfection of denture base materials colonized with Candida albicans.
AB  - STATEMENT OF PROBLEM: Infection of denture materials with Candida albicans is
      common and contributes to denture stomatitis. PURPOSE: This 3-phase investigation
      examined: (1) the efficacy of microwave irradiation against C albicans colonized
      on 3 soft denture liners and 1 heat-polymerized denture base resin, and (2) the
      effect of this irradiation on the hardness of the materials tested. MATERIAL AND
      METHODS: In phase 1, an experimental protocol was developed. Sterilized specimens
      from 2 denture base soft liners and 1 heat-polymerized acrylic resin denture base
      material (n = 45 each) were inoculated with C albicans. Two thirds of the
      specimens were irradiated in a 60 Hz microwave oven for 5 minutes (dry). C
      albicans growth was then assessed with streaked blood agar plates and
      thioglycollate broth. One third of the specimens were not irradiated and served
      as controls. Pretest and posttest Shore A hardness values were obtained and
      compared. For phase 2, 15 specimens from each material group were subjected to
      irradiation (while immersed in water) for 5 minutes; and, 15 from each material
      were subjected to 10- and 15-minute irradiation (dry), with subsequent sterility
      and change in hardness assessments completed as described in phase 1. In phase 3,
      15 specimens from each material group were subjected to repeated 5-minute
      irradiation cycles (while immersed in water), and changes in hardness were
      examined. RESULTS: Only the 5-minute irradiated specimens immersed in water were
      effectively sterilized, as verified by the thioglycollate assay. The effect of
      repeated 5-minute irradiation cycles resulted in a significant change in hardness
      of the PermaSoft specimens. CONCLUSIONS: Five-minute irradiation, while immersed
      in water, killed all C albicans present on the materials tested; and, repeated 5
      minute irradiation significantly affected the hardness of only the PermaSoft
      material.

PMID- 9922436
TI  - The use of a stent-resin-bonded splint combination to stabilize a free gingival
      autograft.
AB  - This article describes the use of a resin-bonded retainer in combination with an
      acrylic resin stent to stabilize a free gingival graft. This retainer also
      prevents migration of muscle attachment after surgery to deepen a section of the
      vestibule where the oral mucosa closely approached the gingival margin. The
      acrylic resin stent is attached to the resin-bonded retainer by means of an
      integrally cast metal framework. After surgery, the retainer is attached to the
      occlusal two thirds of the buccal surfaces of maxillary molar teeth by using the
      acid-etched resin bonding technique. The stent effectively retains the graft, is
      simple to fit, and does not cause any permanent damage to the enamel. It has none
      of the disadvantages of conventional removable acrylic resin stents.

PMID- 9922437
TI  - Intracrown ring for crown and fixed partial denture abutments.
AB  - When a tooth prepared for a crown does not comply with the general principles of
      retention and resistance form, and it is not possible to correct it without
      damage to the biologic structures of the tooth, consideration must be given to
      the purpose of the crown, such as whether it is a single crown, a retainer for a
      fixed restoration, or a retainer for a fixed removable prosthesis with precision
      attachments. The crown prepared with receptacles for internal attachments will
      undoubtedly require more retention and resistance to dislodgment than a single
      crown because of forces that will be applied to it through the removable portion
      of the restoration. The purpose of this article is to present an alternative
      procedure that uses the intracrown ring, which provides additional retention for
      the abutment crown because of the compressible ring. The compressible ring is
      placed in the groove prepared in the lower third of the abutment during the crown
      preparation.

PMID- 9922438
TI  - Fabricating a stable record base for completely edentulous patients treated with
      osseointegrated implants using healing abutments.
AB  - A stable record base is essential for accurate interocclusal centric relation
      records in a completely edentulous patient. In implant prosthodontics, several
      procedures have been suggested for the fabrication of a stable record base.
      However, these procedures necessitate removal of the healing abutments during the
      interocclusal record procedure and the trial denture placement, which makes the
      procedures tedious and time-consuming. When the implant-prosthesis interface is
      subgingival, the patient may also experience discomfort during these procedures.
      This article describes a procedure for fabricating a stable record base that uses
      the healing abutments, which eliminates the necessity of the healing abutment
      removal and its consequences. Advantages and disadvantages of this procedure are
      also discussed.

PMID- 9922439
TI  - Fabrication and use of a surgical template for placing implants to retain an
      auricular prosthesis.
AB  - A procedure is described for the fabrication of a 3-dimensional surgical template
      to guide the placement of implants to retain an auricular prosthesis. This
      procedure requires a diagnostic wax pattern that is checked while on the patient
      to ensure it is positioned correctly and is also the correct size. The wax
      pattern is processed into a clear, methyl methacrylate resin, 3-dimensional
      surgical template. The most effective type of surgical template for planning
      implant placement is a 3-dimensional acrylic template that closely resembles the
      final prosthesis. This template will direct the implant placement where the
      retentive elements are most easily concealed, under the thickest areas of the
      prosthesis, which are the antihelix and antitragus. This location allows the best
      esthetic and functional results. An additional advantage of this technique is
      that it allows the retrieval of the diagnostic wax pattern of the auricle so that
      it can be used to fabricate the definitive prosthesis.

PMID- 9922440
TI  - Procedure for obturating the access canal and preventing the loosening of the
      abutment screw in an implant-retained fixed prosthesis.
AB  - Silicone plugs used for obturating the access canal to retaining screws also act
      as antirotational devices for the screws; however, the procedures to obtain such
      an effect are complex and blind. The purpose of this article is to describe a
      method that would simplify the procedure and allow for checking of results. The
      proposed procedure is simple, efficient, and its results can be verified.

PMID- 9922441
TI  - A simple method of adding palatal rugae to a complete denture.
AB  - Restoring patients' speech is an important goal in complete denture fabrication.
      For those patients who have difficulty with their speech patterns accommodating
      to the introduction of a prosthesis, texture in the palatal region may prove
      helpful. This article describes methods of incorporating palatal rugae in a newly
      fabricated and existing complete denture.

PMID- 9922442
TI  - Custom adaptation of an occlusal plane analyzer to a semiadjustable articulator.
AB  - The use of a semiadjustable articulator has become more popular for prosthodontic
      rehabilitation. An occlusal plane analyzer has long been used to assist the
      operator in the development of an initial mandibular occlusal plane in diagnostic
      contour casts and later as an integral part of both the contours of the
      definitive restorations as well as guidelines for the actual tooth preparations.
      Many manufacturers of semiadjustable articulators offer no such occlusal plane
      analyzers for use with their instruments. This article describes modifications
      for the adaptation of an occlusal plane analyzer to the WhipMix 2240
      semiadjustable articulator, a possibility heretofore unavailable from any
      manufacturer.

PMID- 9922443
TI  - Simple method for creating a casting orientation mark on ringless investment
      molds.

PMID- 9922444
TI  - Substituting Precision Margin Esthetics transmucosal abutments for healing
      abutments.

PMID- 9922445
TI  - A simple, expeditious method for placement of thermoplastic impression material
      for speech aid prostheses.

PMID- 9922446
TI  - Re: Green et al: "Temporomandibular disorders and science: A response to the
      critics".

PMID- 9922447
TI  - Readers round table 

PMID- 9922448
TI  - Nuclear import of the parsley bZIP transcription factor CPRF2 is regulated by
      phytochrome photoreceptors.
AB  - In plants, light perception by photoreceptors leads to differential expression of
      an enormous number of genes. An important step for differential gene expression
      is the regulation of transcription factor activities. To understand these
      processes in light signal transduction we analyzed the three well-known members
      of the common plant regulatory factor (CPRF) family from parsley (Petroselinum
      crispum). Here, we demonstrate that these CPRFs, which belong to the basic-
      region leucine-zipper (bZIP) domain-containing transcription factors, are
      differentially distributed within parsley cells, indicating different regulatory
      functions within the regulatory networks of the plant cell. In particular, we
      show by cell fractionation and immunolocalization approaches that CPRF2 is
      transported from the cytosol into the nucleus upon irradiation due to action of
      phytochrome photoreceptors. Two NH2-terminal domains responsible for cytoplasmic
      localization of CPRF2 in the dark were characterized by deletion analysis using a
      set of CPRF2-green fluorescent protein (GFP) gene fusion constructs transiently
      expressed in parsley protoplasts. We suggest that light-induced nuclear import of
      CPRF2 is an essential step in phytochrome signal transduction.

PMID- 9922450
TI  - Temporal differences in the appearance of NEP-B78 and an LBR-like protein during
      Xenopus nuclear envelope reassembly reflect the ordered recruitment of
      functionally discrete vesicle types.
AB  - In this work, we have used novel mAbs against two proteins of the endoplasmic
      reticulum and outer nuclear membrane, termed NEP-B78 and p65, in addition to a
      polyclonal antibody against the inner nuclear membrane protein LBR (lamin B
      receptor), to study the order and dynamics of NE reassembly in the Xenopus cell
      free system. Using these reagents, we demonstrate differences in the timing of
      recruitment of their cognate membrane proteins to the surface of decondensing
      chromatin in both the cell-free system and XLK-2 cells. We show unequivocally
      that, in the cell-free system, two functionally and biochemically distinct
      vesicle types are necessary for NE assembly. We find that the process of distinct
      vesicle recruitment to chromatin is an ordered one and that NEP-B78 defines a
      vesicle population involved in the earliest events of reassembly in this system.
      Finally, we present evidence that NEP-B78 may be required for the targeting of
      these vesicles to the surface of decondensing chromatin in this system. The
      results have important implications for the understanding of the mechanisms of
      nuclear envelope disassembly and reassembly during mitosis and for the
      development of systems to identify novel molecules that control these processes.

PMID- 9922449
TI  - Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for
      import of Cdk2/cyclin E and Cdc2/cyclin B1.
AB  - Reversible phosphorylation of nuclear proteins is required for both DNA
      replication and entry into mitosis. Consequently, most cyclin-dependent kinase
      (Cdk)/cyclin complexes are localized to the nucleus when active. Although our
      understanding of nuclear transport processes has been greatly enhanced by the
      recent identification of nuclear targeting sequences and soluble nuclear import
      factors with which they interact, the mechanisms used to target Cdk/cyclin
      complexes to the nucleus remain obscure; this is in part because these proteins
      lack obvious nuclear localization sequences. To elucidate the molecular
      mechanisms responsible for Cdk/cyclin transport, we examined nuclear import of
      fluorescent Cdk2/cyclin E and Cdc2/cyclin B1 complexes in digitonin-permeabilized
      mammalian cells and also examined potential physical interactions between these
      Cdks, cyclins, and soluble import factors. We found that the nuclear import
      machinery recognizes these Cdk/cyclin complexes through direct interactions with
      the cyclin component. Surprisingly, cyclins E and B1 are imported into nuclei via
      distinct mechanisms. Cyclin E behaves like a classical basic nuclear localization
      sequence-containing protein, binding to the alpha adaptor subunit of the importin
      alpha/beta heterodimer. In contrast, cyclin B1 is imported via a direct
      interaction with a site in the NH2 terminus of importin-beta that is distinct
      from that used to bind importin-alpha.

PMID- 9922451
TI  - Ca2+-induced Ca2+ release in chromaffin cells seen from inside the ER with
      targeted aequorin.
AB  - The presence and physiological role of Ca2+-induced Ca2+ release (CICR) in
      nonmuscle excitable cells has been investigated only indirectly through
      measurements of cytosolic [Ca2+] ([Ca2+]c). Using targeted aequorin, we have
      directly monitored [Ca2+] changes inside the ER ([Ca2+]ER) in bovine adrenal
      chromaffin cells. Ca2+ entry induced by cell depolarization triggered a transient
      Ca2+ release from the ER that was highly dependent on [Ca2+]ER and sensitized by
      low concentrations of caffeine. Caffeine-induced Ca2+ release was quantal in
      nature due to modulation by [Ca2+]ER. Whereas caffeine released essentially all
      the Ca2+ from the ER, inositol 1,4, 5-trisphosphate (InsP3)- producing agonists
      released only 60-80%. Both InsP3 and caffeine emptied completely the ER in
      digitonin-permeabilized cells whereas cyclic ADP-ribose had no effect. Ryanodine
      induced permanent emptying of the Ca2+ stores in a use-dependent manner after
      activation by caffeine. Fast confocal [Ca2+]c measurements showed that the wave
      of [Ca2+]c induced by 100-ms depolarizing pulses in voltage-clamped cells was
      delayed and reduced in intensity in ryanodine-treated cells. Our results indicate
      that the ER of chromaffin cells behaves mostly as a single homogeneous
      thapsigargin-sensitive Ca2+ pool that can release Ca2+ both via InsP3 receptors
      or CICR.

PMID- 9922452
TI  - Peroxisome synthesis in the absence of preexisting peroxisomes.
AB  - Zellweger syndrome and related diseases are caused by defective import of
      peroxisomal matrix proteins. In all previously reported Zellweger syndrome cell
      lines the defect could be assigned to the matrix protein import pathway since
      peroxisome membranes were present, and import of integral peroxisomal membrane
      proteins was normal. However, we report here a Zellweger syndrome patient
      (PBD061) with an unusual cellular phenotype, an inability to import peroxisomal
      membrane proteins. We also identified human PEX16, a novel integral peroxisomal
      membrane protein, and found that PBD061 had inactivating mutations in the PEX16
      gene. Previous studies have suggested that peroxisomes arise from preexisting
      peroxisomes but we find that expression of PEX16 restores the formation of new
      peroxisomes in PBD061 cells. Peroxisome synthesis and peroxisomal membrane
      protein import could be detected within 2-3 h of PEX16 injection and was followed
      by matrix protein import. These results demonstrate that peroxisomes do not
      necessarily arise from division of preexisting peroxisomes. We propose that
      peroxisomes may form by either of two pathways: one that involves PEX11-mediated
      division of preexisting peroxisomes, and another that involves PEX16-mediated
      formation of peroxisomes in the absence of preexisting peroxisomes.

PMID- 9922453
TI  - An unconventional role for cytoplasmic disulfide bonds in vaccinia virus
      proteins.
AB  - Previous data have shown that reducing agents disrupt the structure of vaccinia
      virus (vv). Here, we have analyzed the disulfide bonding of vv proteins in
      detail. In vv-infected cells cytoplasmically synthesized vv core proteins became
      disulfide bonded in the newly assembled intracellular mature viruses (IMVs). vv
      membrane proteins also assembled disulfide bonds, but independent of IMV
      formation and to a large extent on their cytoplasmic domains. If disulfide
      bonding was prevented, virus assembly was only partially impaired as shown by
      electron microscopy as well as a biochemical assay of IMV formation. Under these
      conditions, however, the membranes around the isolated particles appeared less
      stable and detached from the underlying core. During the viral infection process
      the membrane proteins remained disulfide bonded, whereas the core proteins were
      reduced, concomitant with delivery of the cores into the cytoplasm. Our data show
      that vv has evolved an unique system for the assembly of cytoplasmic disulfide
      bonds that are localized both on the exterior and interior parts of the IMV.

PMID- 9922455
TI  - Characterization of a Chlamydomonas insertional mutant that disrupts flagellar
      central pair microtubule-associated structures.
AB  - Two alleles at a new locus, central pair-associated complex 1 (CPC1), were
      selected in a screen for Chlamydomonas flagellar motility mutations. These
      mutations disrupt structures associated with central pair microtubules and reduce
      flagellar beat frequency, but do not prevent changes in flagellar activity
      associated with either photophobic responses or phototactic accumulation of live
      cells. Comparison of cpc1 and pf6 axonemes shows that cpc1 affects a row of
      projections along C1 microtubules distinct from those missing in pf6, and a row
      of thin fibers that form an arc between the two central pair microtubules.
      Electron microscopic images of the central pair in axonemes from radial spoke
      defective strains reveal previously undescribed central pair structures,
      including projections extending laterally toward radial spoke heads, and a
      diagonal link between the C2 microtubule and the cpc1 projection. By SDS-PAGE,
      cpc1 axonemes show reductions of 350-, 265-, and 79-kD proteins. When extracted
      from wild-type axonemes, these three proteins cosediment on sucrose gradients
      with three other central pair proteins (135, 125, and 56 kD) in a 16S complex.
      Characterization of cpc1 provides new insights into the structure and
      biochemistry of the central pair apparatus, and into its function as a regulator
      of dynein-based motility.

PMID- 9922454
TI  - Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of
      caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner.
AB  - Exit of cytochrome c from mitochondria into the cytosol has been implicated as an
      important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4
      homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9.
      Caspase-9 is thought to propagate the death signal by triggering other caspase
      activation events, the details of which remain obscure. Here, we report that six
      additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell
      free extracts in response to cytochrome c, and that three others (caspases-1, -4,
      and -5) failed to be activated under the same conditions. In vitro association
      assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, 
      2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts
      abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and 
      10, suggesting that caspase-9 is required for all of these downstream caspase
      activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts
      enabled us to order the sequence of caspase activation events downstream of
      caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is
      required for the activation of four other caspases (-2, -6, -8, and -10) in this
      pathway and also participates in a feedback amplification loop involving caspase
      9.

PMID- 9922456
TI  - The small GTP-binding protein rho regulates cortical activities in cultured cells
      during division.
AB  - We have investigated the role of the small GTP-binding protein Rho in cytokinesis
      by microinjecting an inhibitor, C3 ribosyltransferase, into cultured cells.
      Microinjection of C3 into prometaphase or metaphase normal rat kidney epithelial
      cells induced immediate and global cortical movement of actin toward the
      metaphase plate, without an apparent effect on the mitotic spindle. During
      anaphase, concentrated cortical actin filaments migrated with separating
      chromosomes, leaving no apparent concentration of actin filaments along the
      equator. Myosin II in injected epithelial cells showed a diffuse distribution
      throughout cell division. All treated, well-adherent cells underwent cleavage
      like activities and most of them divided successfully. However, cytokinesis
      became abnormal, generating irregular ingressions and ectopic cleavage sites even
      when mitosis was blocked with nocodazole. The effects of C3 appeared to be
      dependent on cell adhesion; less adherent 3T3 fibroblasts exhibited irregular
      cortical ingression only when cells started to increase attachment during
      respreading, but managed to complete cytokinesis. Poorly adherent HeLa cells
      showed neither ectopic cleavage nor completion of cytokinesis. Our results
      indicate that Rho does not simply activate actin-myosin II interactions during
      cytokinesis, but regulates the spatial pattern of cortical activities and
      completion of cytokinesis possibly through modulating the mechanical strength of
      the cortex.

PMID- 9922457
TI  - Dissociation of FAK/p130(CAS)/c-Src complex during mitosis: role of mitosis
      specific serine phosphorylation of FAK.
AB  - At mitosis, focal adhesions disassemble and the signal transduction from focal
      adhesions is inactivated. We have found that components of focal adhesions
      including focal adhesion kinase (FAK), paxillin, and p130(CAS) (CAS) are
      serine/threonine phosphorylated during mitosis when all three proteins are
      tyrosine dephosphorylated. Mitosis-specific phosphorylation continues past
      cytokinesis and is reversed during post-mitotic cell spreading. We have found two
      significant alterations in FAK-mediated signal transduction during mitosis.
      First, the association of FAK with CAS or c-Src is greatly inhibited, with levels
      decreasing to 16 and 13% of the interphase levels, respectively. Second, mitotic
      FAK shows decreased binding to a peptide mimicking the cytoplasmic domain of beta
      integrin when compared with FAK of interphase cells. Mitosis-specific
      phosphorylation is responsible for the disruption of FAK/CAS binding because
      dephosphorylation of mitotic FAK in vitro by protein serine/threonine phosphatase
      1 restores the ability of FAK to associate with CAS, though not with c-Src. These
      results suggest that mitosis-specific modification of FAK uncouples signal
      transduction pathways involving integrin, CAS, and c-Src, and may maintain FAK in
      an inactive state until post-mitotic spreading.

PMID- 9922458
TI  - Neural cell adhesion molecule (N-CAM) is required for cell type segregation and
      normal ultrastructure in pancreatic islets.
AB  - Classical cell dissociation/reaggregation experiments with embryonic tissue and
      cultured cells have established that cellular cohesiveness, mediated by cell
      adhesion molecules, is important in determining the organization of cells within
      tissue and organs. We have employed N-CAM-deficient mice to determine whether N
      CAM plays a functional role in the proper segregation of cells during the
      development of islets of Langerhans. In N-CAM-deficient mice the normal
      localization of glucagon-producing alpha cells in the periphery of pancreatic
      islets is lost, resulting in a more randomized cell distribution. In contrast to
      the expected reduction of cell-cell adhesion in N-CAM-deficient mice, a
      significant increase in the clustering of cadherins, F-actin, and cell-cell
      junctions is observed suggesting enhanced cadherin-mediated adhesion in the
      absence of proper N-CAM function. These data together with the polarized
      distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell
      polarity is also affected. Finally, degranulation of beta cells suggests that N
      CAM is required for normal turnover of insulin-containing secretory granules.
      Taken together, our results confirm in vivo the hypothesis that a cell adhesion
      molecule, in this case N-CAM, is required for cell type segregation during
      organogenesis. Possible mechanisms underlying this phenomenon may include changes
      in cadherin-mediated adhesion and cell polarity.

PMID- 9922459
TI  - Neurolin Ig domain 2 participates in retinal axon guidance and Ig domains 1 and 3
      in fasciculation.
AB  - The optic disk-directed growth of retinal ganglion cell axons is markedly
      disturbed in the presence of polyclonal antineurolin antibodies, which mildly
      affect fasciculation (Ott, H., M. Bastmeyer, and C.A.O. Stuermer, 1998. J.
      Neurosci. 18:3363-3372). New monoclonal antibodies (mAbs) against goldfish
      neurolin, an immunoglobulin (Ig) superfamily cell adhesion/recognition molecule
      with five Ig domains, were generated to assign function (guidance versus
      fasciculation) to specific Ig domains. By their ability or failure to recognize
      Chinese hamster ovary cells expressing recombinant neurolin with deletions of
      defined Ig domains, mAbs were identified as being directed against Ig domains 1,
      2, or 3, respectively. Repeated intraocular injections of a mAb against Ig domain
      2 disturb the disk-directed growth: axons grow in aberrant routes and fail to
      reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3
      disturb the formation of tight fascicles. mAb against Ig domain 2 significantly
      increases the incidence of growth cone departure from the disk-oriented fascicle
      track, while mAbs against Ig domains 1 and 3 do not. This was demonstrated by
      time-lapse videorecording of labeled growth cones. Thus, Ig domain 2 of neurolin
      is apparently essential for growth cone guidance towards the disk, presumably by
      being part of a receptor (or complex) for an axon guidance component.

PMID- 9922460
TI  - Analysis of C-cadherin regulation during tissue morphogenesis with an activating
      antibody.
AB  - The regulation of cadherin-mediated adhesion at the cell surface underlies
      several morphogenetic processes. To investigate the role of cadherin regulation
      in morphogenesis and to begin to analyze the molecular mechanisms of cadherin
      regulation, we have screened for monoclonal antibodies (mAbs) that allow us to
      manipulate the adhesive state of the cadherin molecule. Xenopus C-cadherin is
      regulated during convergent extension movements of gastrulation. Treatment of
      animal pole tissue explants (animal caps) with the mesoderm-inducing factor
      activin induces tissue elongation and decreases the strength of C-cadherin
      mediated adhesion between blastomeres (Brieher, W.M., and B.M. Gumbiner. 1994. J.
      Cell Biol. 126:519-527). We have generated a mAb to C-cadherin, AA5, that
      restores strong adhesion to activin-treated blastomeres. This C-cadherin
      activating antibody strongly inhibits the elongation of animal caps in response
      to activin without affecting mesodermal gene expression. Thus, the activin
      induced decrease in C-cadherin adhesive activity appears to be required for
      animal cap elongation. Regulation of C-cadherin and its activation by mAb AA5
      involve changes in the state of C-cadherin that encompass more than changes in
      its homophilic binding site. Although mAb AA5 elicited a small enhancement in the
      functional activity of the soluble C-cadherin ectodomain (CEC1-5), it was not
      able to restore cell adhesion activity to mutant C-cadherin lacking its
      cytoplasmic tail. Furthermore, activin treatment regulates the adhesion of
      Xenopus blastomeres to surfaces coated with two other anti-C-cadherin mAbs, even
      though these antibodies probably do not mediate adhesion through a normal
      homophilic binding mechanism. Moreover, mAb AA5 restores strong adhesion to these
      antibodies. mAb AA5 only activates adhesion of blastomeres to immobilized CEC1-5
      when it binds to C-cadherin on the cell surface. It does not work when added to
      CEC1-5 on the substrate. Together these findings suggest that the regulation of C
      cadherin by activin and its activation by mAb AA5 involve changes in its cellular
      organization or interactions with other cell components that are not intrinsic to
      the isolated protein.

PMID- 9922461
TI  - The junction-associated protein AF-6 interacts and clusters with specific Eph
      receptor tyrosine kinases at specialized sites of cell-cell contact in the brain.
AB  - The AF-6/afadin protein, which contains a single PDZ domain, forms a peripheral
      component of cell membranes at specialized sites of cell-cell junctions. To
      identify potential receptor-binding targets of AF-6 we screened the PDZ domain of
      AF-6 against a range of COOH-terminal peptides selected from receptors having
      potential PDZ domain-binding termini. The PDZ domain of AF-6 interacts with a
      subset of members of the Eph subfamily of RTKs via its COOH terminus both in
      vitro and in vivo. Cotransfection of a green fluorescent protein-tagged AF-6
      fusion protein with full-length Eph receptors into heterologous cells induces a
      clustering of the Eph receptors and AF-6 at sites of cell-cell contact.
      Immunohistochemical analysis in the adult rat brain reveals coclustering of AF-6
      with Eph receptors at postsynaptic membrane sites of excitatory synapses in the
      hippocampus. Furthermore, AF-6 is a substrate for a subgroup of Eph receptors and
      phosphorylation of AF-6 is dependent on a functional kinase domain of the
      receptor. The physical interaction of endogenous AF-6 with Eph receptors is
      demonstrated by coimmunoprecipitation from whole rat brain lysates. AF-6 is a
      candidate for mediating the clustering of Eph receptors at postsynaptic
      specializations in the adult rat brain.

PMID- 9922463
TI  - Conditional lethality of cell shape mutations of Salmonella typhimurium: rodA and
      mre mutants are lethal on solid but not in liquid medium.
AB  - Round-cell (rodA, mre, divD) derivatives of a conditional alaS mutant of
      Salmonella typhimurium were studied under conditions allowing expression of
      tolerance to lethal cell shape mutations (41 degrees C), and under nontolerant
      conditions (30 degrees C). The rodA22::Tn10d(Kan) derivative grew normally (OD650
      nm) in LB-broth at 30 degrees C; however, doubling of total cell count took much
      longer (130 min) than at 41 degrees C (57 min). Although the cells were able to
      divide in LB-broth at 30 degrees C, viable count on LB-agar at 30 degrees C was
      10(3)-fold lower than on LB-agar at 41 degrees C. Phase-contrast microscopy of
      rodA cells incubated under different conditions showed that their size increased
      on LB-soft agar at 30 degrees C, but they failed to divide and finally lysed. In
      contrast, division occurred in LB-broth at 30 degrees C and also in LB-broth and
      LB-soft agar at 41 degrees C. The mre-17::Tn10d(Kan) derivative acted like the
      rodA strain whereas the divD135::Tn10d(Kan) mutant behaved normally both at 30
      degrees C and 41 degrees C. It is concluded that rodA and mre mutations delay
      cell division, but are lethal only on solid medium. Mutations conferring
      tolerance to "lethal" rodA and mre mutations improve division performance both in
      liquid and solid media.

PMID- 9922462
TI  - Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of
      glioma cells in central nervous system white matter.
AB  - Invasive glioma cells migrate preferentially along central nervous system (CNS)
      white matter fiber tracts irrespective of the fact that CNS myelin contains
      proteins that inhibit cell migration and neurite outgrowth. Previous work has
      demonstrated that to migrate on a myelin substrate and to overcome its inhibitory
      effect, rat C6 and human glioblastoma cells require a membrane-bound
      metalloproteolytic activity (C6-MP) which shares several biochemical and
      pharmacological characteristics with MT1-MMP. We show now that MT1-MMP is
      expressed on the surface of rat C6 glioblastoma cells and is coenriched with C6
      MP activity. Immunodepletion of C6-MP activity is achieved with an anti-MT1-MMP
      antibody. These data suggest that MT1-MMP and the C6-MP are closely related or
      identical. When mouse 3T3 fibroblasts were transfected with MT1-MMP they acquired
      the ability to spread and migrate on the nonpermissive myelin substrate and to
      infiltrate into adult rat optic nerve explants. MT1-MMP-transfected fibroblasts
      and C6 glioma cells were able to digest bNI-220, one of the most potent CNS
      myelin inhibitory proteins. Plasma membranes of both MT1-MMP-transfected
      fibroblasts and C6 glioma cells inactivated inhibitory myelin extracts, and this
      activity was sensitive to the same protease inhibitors. Interestingly,
      pretreatment of CNS myelin with gelatinase A/MMP-2 could not inactivate its
      inhibitory property. These data imply an important role of MT1-MMP in spreading
      and migration of glioma cells on white matter constituents in vitro and point to
      a function of MT1-MMP in the invasive behavior of malignant gliomas in the CNS in
      vivo.

PMID- 9922464
TI  - Transcriptional activity at supraoptimal temperature of growth in the antarctic
      psychrotrophic bacterium Pseudomonas syringae.
AB  - Transcriptional activity was monitored in cells of the Antarctic psychrotrophic
      bacterium Pseudomonas syringae (Lz4W), which does not grow above 30 degrees C. It
      was observed that the bacterium was capable of synthesising RNA at a temperature
      range of 0-37 degrees C, both in vitro and in vivo. The net incorporation of the
      radioactive precursor, [3H]uridine, into RNA was found to be affected at 37
      degrees C. A pulse-chase experiment following a 32P labeling of RNA in vivo
      indicated that the ribosomal RNAs (rRNAs) degrade faster at and above 30 degrees
      C. It was also found that the increased ribonuclease (RNase) activity at high
      temperature might be responsible for this degradation. The attack on ribosomal
      RNAs by RNase took place after their assembly into ribosomal particles. It is
      suggested that the degradation of rRNAs at supraoptimal temperatures might be a
      detrimental factor for growth above 30 degrees C.

PMID- 9922465
TI  - Medium-chain-length poly(beta-hydroxyalkanoate) synthesis from triacylglycerols
      by Pseudomonas saccharophila.
AB  - Pseudomonas saccharophila NRRL B-628 is capable of utilizing agricultural lipids
      for growth. The organism exhibited good growth with triacylglycerol substrates
      that contained saturated fatty acyl moieties such as coconut oil (CO; C10-12
      fatty acids) and tallow (T; C16-18 fatty acids). Electron micrographs of the
      triacylglycerol-grown cells showed the presence of intracellular granules
      indicative of poly(beta-hydroxyalkanoate) (PHA) production. Cells grown in a 250
      ml CO-containing medium produced ca. 0.2 g of medium-chain-length (mcl)-PHA. Gas
      chromatographic analysis showed that beta-hydroxyoctanoic acid (30%), beta
      hydroxydecanoic acid (40%), and beta-hydroxydodecanoic acid (16%) were the major
      monomer repeat-units of the CO-derived polymer. The estimated mean molecular mass
      of the CO-derived mcl-PHA as determined by gel permeation chromatography was 13.1
      x 10(4) g/mol with a polydispersity of 3.16.

PMID- 9922466
TI  - Expression of the copper metallothionein CUPI from Saccharomyces cerevisiae in
      the cyanobacterium Synechococcus R2-PIM8(smtA).
AB  - The coding sequence for Saccharomyces cerevisiae copper metallothionein (CUPI),
      the protein responsible for enhanced sequestration of Cu2+ in yeast, was placed
      under the control of an inducible synthetic Escherichia coli promoter in the
      cyanobacterial vector pTrcIK. Strain R2-PIM8(smtA) of Synechococcus sp. PCC 7942
      was transformed with the resulting construct pMcK2, and the yeast CUPI gene was
      integrated into its genome via homologous recombination. The pMcK2 plasmid
      directed the synthesis of a protein product of the expected size in an in vitro
      E. coli transcription/translation system. In the transgenic cyanobacteria, the
      integrated CUPI gene was transcribed and produced a protein product with the
      expected metallothionein characteristics, as determined by 109Cd2+ binding
      assays. At this level of expression, the yeast metallothionein, although
      functional, did not increase the tolerance range of the transgenic Synechococcus
      to Cu2+ or Cd2+ beyond that of the untransformed R2-PIM8(smtA).

PMID- 9922467
TI  - Introduction and expression of the cry1Ac gene of Bacillus thuringiensis in a
      cereal-associated bacterium, Bacillus polymyxa.
AB  - The abilities of Bacillus polymyxa and Bacillus thuringiensis to survive on the
      rice phyllospere were compared; it was found that B. polymyxa colonizes the crop
      better. This study also showed that B. polymyxa inoculation to rice plants
      increased the shoot and the root growth of the crop. Efforts were made to
      introduce the cry1Ac gene of B. thuringiensis subsp. kurstaki into B. polymyxa so
      that the application of such transgenic B. polymyxa strains would prove to be
      dually beneficial to rice crops both as a biopesticide and as a biofertilizer.
      Immunoblot analysis of the recombinant organism containing the cry1Ac gene,
      strain BP113, indicated efficient expression of this gene in the heterologous
      host. Bioassays with the first instar larvae of the yellow stem borer of rice
      (Scirpophaga incertulas) revealed that the protein preparations from BP113 were
      toxic.

PMID- 9922469
TI  - Isolation of DNA from the uncultured "Candidatus Liberobacter" species associated
      with citrus Huanglongbing by RAPD.
AB  - "Candidatus Liberobacter," the uncultured bacterium associated with citrus
      Huanglongbing (HLB) disease, is an alpha-Proteobacteria, and two species,
      "Candidatus L. africanum" and "Candidatus L. asiaticum, " have been characterized
      by sequence analysis of the 16S rDNA and beta operon (rplKAJL-rpoBC) genes. These
      genes were isolated by PCR and random cloning of DNA from infected plants.
      However, this strategy is laborious and allowed selection of only three
      Liberobacter DNA fragments. In this paper, we described isolation of additional
      genes using Random Amplified Polymorphic DNA (RAPD). In total, 102 random 10-mer
      primers were used in PCR reactions on healthy and Liberobacter-infected plant
      DNA. Eight DNA bands amplified from infected plant DNA were cloned and analyzed.
      Six of them were found to be part of the Liberobacter genome by sequence and
      hybridization experiments. On these DNA fragments, four genes were identified:
      nusG, pgm, omp, and a hypothetical protein gene. These results indicate that RAPD
      can be used to clone DNA of uncultured organisms.

PMID- 9922468
TI  - Adaptive response to cold temperatures in Vibrio vulnificus.
AB  - The effectiveness of rapid chilling or freezing of oysters to reduce Vibrio
      vulnificus levels in shellfish may be compromised by product handling procedures
      that permit cold adaptation. When a V. vulnificus culture was shifted from 35
      degrees C to 6 degrees C conditions, it underwent transition to a non-culturable
      state. Cells adapted to 15 degrees C prior to change to 6 degrees C condition,
      however, remain viable and culturable. In addition, cultures adapted to 15
      degrees C were able to survive better upon freezing at -78 degrees C compared
      with cultures frozen directly from 35 degrees C. Inhibition of protein synthesis
      by addition of chloramphenicol in a V. vulnificus culture immediately prior to
      the exposure to the adaptive temperature eliminated inducible cold tolerance.
      These results suggest that cold-adaptive "protective" proteins may enhance
      survival and tolerance at cold temperatures. In addition, removal of iron from
      the growth medium by adding 2,2'-Dipyridyl prior to cold adaptation decreased the
      viability by approximately 2 logarithm levels. This suggests that iron plays an
      important role in adaptation at cold temperatures. Analysis of total cellular
      proteins on an SDS polyacrylamide gel electrophoresis, labeled with 35S
      methionine during exposure at 15 degrees C, showed elevated expressions of a 6
      kDa and a 40-kDa protein and decreased expression of an 80-kDa protein. These
      results suggest that, for V. vulnificus, survival and tolerance at cold
      temperatures could be due to the expression of cold-adaptive proteins other than
      previously documented major cold shock proteins such as CS7.4 and CsdA. In this
      study, for the first time we have shown that exposure to an intermediate cold
      temperature (15 degrees C) causes a cold adaptive response, helping this pathogen
      remain in culturable state when exposed to a much colder temperature (6 degrees
      C). This adaptive nature to cold temperatures could be important for shellfish
      industry efforts to reduce the risk of V. vulnificus infection from consuming raw
      oysters.

PMID- 9922470
TI  - Extended serotyping scheme for Vibrio anguillarum with the definition and
      characterization of seven provisional O-serogroups.
AB  - The present paper summarizes the serotyping scheme of the fish pathogenic
      bacterium Vibrio anguillarum and defines seven additional O-serogroups. Strains,
      collected in our laboratories that were nontypable with antisera against the
      previously defined 16 O-serotypes, were used for generating new antisera and were
      characterized further by means of LPS profiles, Western blots, and serological
      reactions. On the basis of the results, it is suggested that the seven new O
      serogroups are to be included in the existing serotyping system as serotypes O17
      O23. However, the existence of further V. anguillarum strains that were not
      typable with any of the 23 O-antisera suggested the existence of additional O
      serotypes within this species. The relevance of the description of additional O
      serotypes for the species V. anguillarum is discussed.

PMID- 9922471
TI  - News & notes: production, purification, and properties of an endo-1, 3-beta
      glucanase from the basidiomycete Agaricus bisporus.
AB  - Agaricus bisporus H 25 produced extracellular endo-1, 3-beta-glucanase when grown
      in a static culture at 25 degrees C in a minimal synthetic medium supplemented
      with A. bisporus cell walls plus fructose. Endo-1,3-beta-glucanase was purified
      17.85-fold from 20-day-old culture filtrates by precipitation at 80% ammonium
      sulfate saturation, Sephadex G-75 gel filtration, and preparative PAGE followed
      by electroelution. The purified enzyme yielded a single band in both native and
      SDS-polyacrylamide gels with a molecular mass of 32 kDa (SDS-PAGE) and 33.7 kDa
      (MALDI-MS), showing an isoelectric point of 3.7. The enzyme was active against
      beta-1,3- linkages and, to a lesser extent, against beta-1,6-, exhibiting an
      endohydrolytic mode of action and a glycoprotein nature. Significant activities
      of the endo-glucanase against laminarin and pustulan were observed between pH 4
      and 5.5, and between 40 degrees and 50 degrees C for laminarin, and between 30
      degrees and 50 degrees C for pustulan. The optimum pH and temperature were 4.5
      and 45 degrees C for both substrates.

PMID- 9922472
TI  - The effects of low-frequency ultrasound on Staphylococcus epidermidis.
AB  - Low frequency ultrasound (LFUS) significantly enhances skin permeability to a
      variety of drugs; however, its bacterial effects have not been well studied.
      Staphylococcus epidermidis organisms were grown and standardized to 10(5) cfu/ml
      24 h prior to investigation and suspended in normal saline. LFUS was applied with
      two probes immersed in the bacterial suspensions over a range of suspension
      volumes, intensities, and exposure times. The suspension temperature was
      measured, and a sample was removed, streaked onto blood agar plates, and
      incubated at 37 degrees C for 24 h. Quantitative bacterial counts were then
      obtained. LFUS resulted in significant reductions in bacterial counts that
      correlated with fluid temperature. Probe size and ultrasound intensity appeared
      to affect bacterial counts, but were also correlated with temperature. Bacterial
      growth was minimal with temperatures exceeding 45 degrees C. While LFUS can
      reduce bacterial counts, these conditions have the potential to cause burns in
      humans.

PMID- 9922473
TI  - [Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia
      type-1 (MEN-1)].
AB  - MEN-1 is a hereditary autosomal dominant syndrome characterized by the
      involvement of parathyroid glands, pancreatic islet cells and anterior pituitary
      gland. Today molecular genetics permit gene carrier analysis to compare the data
      obtained with the clinical biochemical tests. The twenty living members of the
      first, second and third generation of a family with MEN-1 were studied to
      determine the presence of genetic markers in MEN-1 loci 11q13, by linkage
      analysis and in affected individuals by biochemical tests and clinical
      examination. Two very informative polymorphic markers immediately flanking the
      MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes
      segregated by two members of the second generation, inherited from their father
      and two of the third generation: the affected one and one presymptomatic. The
      third generation had the affected member with renal stones and elevated PTH, PRL
      and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH.
      Among the members who inherited the normal allele we found one with elevated
      gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic.
      Of one Argentine family studied, molecular diagnosis allowed us to detect one
      presymptomatic carrier in the members at risk. As suggested by the available
      literature, accuracy of molecular diagnosis seems to make it the test of choice
      to exclude those members at risk for MEN-1 inheriting the normal allele.

PMID- 9922474
TI  - [Treatment of post menopausal osteoporosis with intravenous pamidronate in
      patients with esophagogastric pathology].
AB  - Pamidronate is an effective inhibitor of bone resorption; for this reason it is
      used in the treatment of high bone turnover diseases and osteoporosis. Because of
      potential gastric and esophagic side effects their oral use is limited in
      patients with active pathology in these organs. With the aim to evaluate the
      usefulness and to establish the ideal schedule of treatment of intravenous
      pamidronate, we assayed pamidronate infusions (APDIV) in 20 postmenopausal women
      with active gastroesophagical diseases. Ten of these patients received 30 or 45
      mg weekly until they achieved an average dose of 157.50 +/- 9.28 mg/year in one
      month (range: 120-180 mg) (Group A). Another comparable ten women's group
      received 30 or 45 mg every three months or 90 mg every six months; the achieved
      average dose in this group was 166.50 +/- 6.87 mg/year (range: 120-180 mg) (Group
      B). All patients received 1,000 mg elemental calcium daily. Bone mineral density
      in lumbar spine significantly increased in both groups, but this increment (delta
      DMO%) was higher in group B. Bone mineral density in femoral neck was only
      increased in group A. Parathyroid hormone (iPTH) significantly increased at the
      third month but returned to basal values at the end of the year in both groups.
      Parameters of bone remodeling such as osteocalcin (BGP), pyridinoline and
      deoxipyridinolin decreased progressively and remained low at the end of the year.
      The treatment was well tolerated: only two patients in group A and one in Group B
      experienced fever and pseudoflu syndrome; phlebitis was present in one patient in
      the second group. In conclusion, intravenous Pamidronate is an effective and safe
      treatment for postmenopausal osteoporosis specially in these patients with
      esophagicor gastric disorders. Future trials are needed to clarify the ideal dose
      and schedule of treatment.

PMID- 9922475
TI  - [Olpadronate prevents cortical and trabecular bone loss induced by
      supraphysiological dosis of thyroxine in ovariectomized rats].
AB  - The aim of the present report was to clarify the effect of excess T4 on axial and
      peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective
      effect of olpadronate (Olpa) on axial and peripheral bone mass in thyroxine
      treated rats was also investigated. Female Sprague-Dawley rats were used: SHAM,
      OVX + Vh, OVX + Olpa (0.3 mg/kg/week), OVX + T4 (250 micrograms/kg/day) and OVX +
      T4 + Olpa rats. OVX + Vh group presented a BMD lower than SHAM in the tibia (p <
      0.01) but not in femur or lumbar spine; the middle tibia BMD did not change but
      it was lower at the distal (pns.) and proximal levels (p < 0.003) in OVX + Vh.
      OVX + T4 rats presented a BMD significantly lower than OVX + Vh rats in total
      tibia (p < 0.02), femur (p < 0.006) and lumbar spine (p < 0.006). Moreover the
      BMD was lower in all studied areas of the tibia, but it was statistically
      significant only at the middle level (p < 0.004). OVX + Olpa rats had a BMD
      higher than OVX + Vh rats in femur (p < 0.002), lumbar spine (p < 0.0001), total
      (p < 0.001) and proximal tibia (p < 0.001). Surprisingly, total and proximal
      tibia BMD values in OVX + Olpa rats presented a BMD significantly higher than OVX
      + T4 rats in femur (p < 0.001), lumbar spine (p < 0.001), tibia (p < 0.001) and
      proximal tibia (p < 0.0001). It is important to point out that OVX + T4 + Olpa
      BMD was significantly higher than in SHAM rats at the lumbar spine, total and
      proximal tibia (p < 0.01). The present study suggests that although
      supraphysiological thyroid hormone affected both cortical and trabecular bone,
      under estrogen-depleted conditions, the cortical bone appears to be more
      sensitive than the trabecular bone to T4 treatment. We also found that Olpa could
      prevent the peripheral and axial bone loss induced by thyroid hormone excess.

PMID- 9922476
TI  - [The internist and ovarian cancer].
AB  - For the purpose of evaluating the role and participation of the internist in the
      diagnosis of Epithelial Ovarian Cancer (EOC), 81 medical records belonging to
      patients with EOC, were analyzed. The mean age of the patients was 63.5 years old
      (SD 12.33). Of these patients 21% were asked about their personal and familiar
      oncology history during their first office visit. Thirteen patients (16%) were
      asymptomatic in the first consultation. The more frequent symptoms were pain and
      abdominal distention. During this first examination, 46 patients (56.8%)
      presented some evident physical sign, and EOC was suspected in 35 patients (P =
      0.00000004): the most frequent sign was an abdominopelvic mass in 34 patients
      (74%). Forty-six patients with EOC (56.8%) consulted an internist and twenty-four
      patients (29.6%) a gynecologist at first evaluation, without significant
      differences in diagnostic suspicion. Internists did not perform an abdomino
      pelvic palpation. Gynecologists performed the abdomino-pelvic palpation in 74
      patients, and 58 (78.4%) were found to be abnormal. The mean age of patients
      examined by internists was 68.2 years old, that is ten years older than the
      patients examined by gynecologists (P = 0.0007) and 70% were in Stages III and IV
      (P = 0.02). Gynecologists examined 9 asymptomatic patients (P = 0.0003) and 42%
      in Stages III and IV. The more frequent reasons for consultation to internists
      were abdominal pain (23 patients) and distention (17 patients). On the other hand
      metrorrhagia (9 patients) was the most common reason to consult a gynecologist.
      In conclusion, internists were frequent receptors of women with ovarian cancer at
      the first consultation. Their patients were older and with a more advanced
      disease stage. The interrogation concerning the oncology history was insufficient
      and the gastrointestinal symptoms were the most frequent cause for consulting an
      internist. The presence of some physical signs was associated with more
      diagnostic suspicion. The gynecologists examined more asymptomatic patients.

PMID- 9922477
TI  - In acute lymphoblastic leukemia deletion of the tumor suppressor gene P16 is
      associated with abnormal interferon genes.
AB  - The putative tumor-suppressor gene p16 was mapped to human chromosome 9p21, close
      to the interferon alpha cluster. The frequency and association of gene
      alterations of p16, interferon alpha and interferon beta were investigated in a
      total of 39 Acute Lymphoblastic Leukemia (ALL) patients. Of these, 10 patients
      (25.6%) presented abnormalities of at least one of the three genes studied. In 32
      ALL cases studies of the three genes could be accomplished. In 23 out of 32 ALL
      cases the 3 genes studied were normally preserved. In the remaining 9 ALL, p16
      was affected in 8 cases by homozygous deletions. In 2 patients, p16 deletion was
      associated with homozygous deletions for interferon alpha and interferon beta
      genes and in 1 case with total deletion of interferon beta 1 gene and partial
      deletion of interferon alpha. In the remaining 5 cases, p16 was the only gene
      deleted with no alteration of type I interferon genes. These data indicate that
      p16 gene is deleted in a higher frequency than type I interferon genes in ALL.
      Moreover, within the ALL group with p16 gene deletion, 37.5% are associated with
      interferon deletions and in general, ALL with alpha and/or beta interferon gene
      deletions are associated with p16 deletions. Therefore, p16 gene deletion with
      preserved type I interferon genes in some ALL suggests that the absence of this
      cdk inhibitor may disturb the normal cell cycle and favor blast transformation.

PMID- 9922478
TI  - [Survey of sexually transmitted diseases in the region of Rio Cuarto].
AB  - Sexually transmitted diseases (STD) are acquired mainly through sexual
      intercourse, being one of the most frequent groups of infectious diseases
      worldwide and consequently an important public health problem. The aim of this
      paper was to determine the current state of STD and to compare different
      diagnostic methods in the population studied. A total of 1060 samples from
      vaginal flows, endocervical material and urethral discharge were studied during 3
      years. Of the total samples, 583 were positive, 493 in women and 90 in men.
      Microorganisms found in women were: Gardnerella vaginalis (39.3%), Candida
      albicans (21.1%), Trichomonas vaginalis (17.3%), Candida trachomatis (11.3%),
      Neisseria gonorrhoeae (3.2%): Mycoplasma hominis and Ureaplasma urelyticum (6.5%)
      and Treponema pallidum (1.4%), the associations found were, Gardnerella vaginalis
      with Trichomonas vaginalis 5.5%; Gardnerella vaginalis with Candida albicans
      4.9%; Trichomonas vaginalis with Neisseria gonorrhoeae (2.2%) and Gardnerella
      vaginalis with Chlamydia trachomatis (1.9%). In men, gonococcal urethritis (UG)
      represented 37.7% non UG 55.6% and Treponema pallidum 6.7%. These results
      indicate a decrease in sifilis and in UG when compared to previous studies
      showing that gonococcal cervicitis had also decreased. We found an important
      increase in the prevalence of urethritis and non gonococcal cervicitis in
      agreement with world statistics which consider these diseases as the most common
      venereal ones. It is necessary to increase the search for Chlamydia trachomatis
      in pregnant women due to vertical transmission. It should be noted that, in spite
      of certain fluctuations, the incidence of the STD in our area is still
      unacceptably high.

PMID- 9922479
TI  - [Recurrence of vesicular microlithiasis. Controlled study with different dosis of
      ursodeoxycholic acid].
AB  - Recurrent gallstones are the limiting factor for every non surgical treatment. In
      order to determine the optimal prevention therapy, 30 patients after successful
      dissolution therapy of microcholelithiasis (MCL) with ursodeoxycholic acid
      (UDCA), were randomized by the double blind method to receive UDCA therapy. This
      was administered either as 150 mg (N = 15, group I) or 300 mg per day (N = 15,
      group II). There was a follow-up period of 12 months with clinical examination
      every month and upper abdominal sonography on days 180 and 360. Recurrent
      gallstones, after a 12-month period, was 6.7% (1/15) in group II versus 66%
      (10/15) in group I (P < 0.005). When recurrence was examined according to the
      number of gallstones, it reached 8% (1/12) in the solitary MCL vs 55.5% (10/18)
      in multiple MCL (P < 0.005). The recurrence was always symptomatic (biliary pain)
      and developed in 11 out of 30 pts, as MCL in 7 and as biliary sludge in the
      remainder 4. We conclude that a daily dose of 300 mg of UDCA was effective in
      reducing the recurrent gallstones in more than 90% of cases treated for 12
      months. The significant risk factors associated with recurrence were the UDCA low
      dose and multiple stones. Biliary sludge represented 36% of the recurrence.

PMID- 9922480
TI  - [Diagnostic imaging in Cushing's disease and its correlation with postsurgical
      clinical course].
AB  - The purpose of this paper was to assess the accuracy of computed tomography (CT)
      and magnetic resonance (MR) in the preoperative identification of corticotropin
      secreting pituitary adenomas and to evaluate the concordance with the
      postoperative outcome. A total of 44 images of patients with Cushing's disease
      were retrospectively taken into consideration; 23 CT and 29 MR were evaluated.
      Patients were subdivided into remission or persistence, following the
      postoperative outcome and biochemical tests. In 13 out of 23 CT performed, an
      adenoma was found, the remaining 10 being negative. TC sensitivity was 56.5%.
      Twenty five MR were positive and 4 were negative. The overall sensitivity of MR
      in detecting ACTH-secreting adenoma was greater (86.0%, P: 0.0373, after Yates
      correction). After operation, 31 patients (70.5%, Cl 0.70 +/- 0.13) were
      considered to be in remission (27 total remission and 4 partial remission); 23
      had had preoperative visualization of the pituitary tumor and 8 negative
      neuroradiological evaluation. Thirteen patients had persistence of disease as
      shown by sustained hypercotisolism in biochemical tests. In 11 of these patients,
      an adenoma had been preoperatively identified whereas in the remaining 2 no
      evidence of tumor lesion had been detected. An histologically proven tumor was
      found in 33 patients but findings were negative in the remaining 11 cases. Lack
      of histological evidence of an ACTH-secreting adenoma was more frequent in
      patients with persistent hypercortisolism (P < 0.0078). IN CONCLUSION: 1) MR
      seems to be more sensitive than CT for detecting ACTH-secreting adenomas (P:
      0.037, after Yates correction); 2) no relationship was disclosed between the
      absence of imaging signs of adenoma and the postsurgical outcome; 3) the
      remission rate was significantly higher in patients with positive than in those
      with negative histological findings.

PMID- 9922481
TI  - [Prevalence of hypertension in 3154 young students].
AB  - Blood pressure (BP) levels were evaluated in 3154 students (mean age 21 years
      old) of La Plata University, School of Medicine. BP was registered three times in
      each student and the mean was used for all the analyses. Systolic (SBP) and
      diastolic pressure (DBP) were significantly higher in men. Mean SBP was 126 +/-
      13 mm Hg for men and 115 +/- 11 mm Hg for women. Mean DBP was 77 +/- 10 mm Hg and
      74 +/- 9 mmHg for men and women, respectively. The global prevalence of HBP (BP >
      or = 140 and/or 90 mm Hg) was 12% when both sexes were considered together, but
      it was significantly higher in men than in women (20% and 6% respectively; p <
      0.001). Mean BP corresponding to the 95th percentile in each sex was also
      estimated. Taking these values to define high blood pressure (HBP) the cut-off
      point between normal and HBP will be different for each sex (148/93 mm Hg for men
      and 133/88 mm Hg for women). The prevalence of HBP in this survey is high if we
      compare with that of the NHANES III (1988-91, USA, 2%) for a group of the same
      age. However, it is very similar to that of NHANES II (1976-80, USA, 12%), before
      the intensification of educational and primary prevention programs took place.
      The global prevalence of optimal BP (BP < 120/80 mm Hg) was just 44%. The
      relation between Body Mass Index (BMI) and BP levels was also studied, and the
      result was a positive correlation, statistically significant. Mean BP increased
      1.16 mm Hg per unit of increase of BMI. When asking about family history (only
      mother or father) of HBP we could not find any significant difference between the
      students with HBP and the others. Cardiovascular diseases are the first cause of
      death in our country and HBP is one of the most important risk factors. The high
      prevalence of HBP in this young population must be considered when planning
      health care programs.

PMID- 9922482
TI  - Progression of intravaginal infection by herpes simplex-2 in genetically athymic
      mice.
AB  - The purpose of this paper was to study the pathogenesis of wild-type Herpes
      simplex-2 (HSV-2) primary intravaginal (IVAG) infection in genetically athymic
      (nude) mice. Nude (nu/nu) N: NIH(S) and Balb/c mice, as well as their euthymic
      counterparts were IVAG infected with 5 x 10(5) pfu of HSV-2. The progression of
      the infection was followed by HSV-2 immunolabeling using the peroxidase
      antiperoxidase technique in tissue sections of the whole body, electron
      microscopy, and viremia titration at two different time points. 70% of athymic
      NIH mice, 30% of euthymic NIH mice, and 80% of both athymic and euthymic Balb/c
      mice developed acute vulvovaginitis and died between 8-10 days post-infection
      (pi). Viremia was not detected in either athymic or euthymic mice. HSV-2
      replicated in the vulvovaginal, vesical and perianal epithelia, then progressed
      towards the central nervous system mainly along autonomic nerves and ganglia. HSV
      2 antigens were not detected in liver, spleen, kidney, skin, heart, lung or bone
      marrow. The conclusion is that the T-cell immune response seems to limit the IVAG
      infection of NIH mice at the inoculation site, but is not involved in preventing
      HSV-2 dissemination through the blood.

PMID- 9922483
TI  - Telomerase activity in thymomas and mammary gland adenocarcinomas induced by
      polyoma virus in AKR mice.
AB  - Telomerase is an enzyme that stabilizes telomere length in transformed cells and
      tumors. Its role in tumor development is far from clear. In this paper, a new
      experimental model to study telomerase activity during tumorigenesis is
      presented. After infection with Polyoma virus, AKR mice developed thymomas and
      mammary gland adenocarcinomas. Polyoma antigens were observed by the peroxidase
      antiperoxidase technique on tissue sections, and by Western blot on tumor
      extracts. The TRAP assay was performed to detect telomerase activity. It was not
      present in normal mammary gland, but it was positive in mammary gland
      adenocarcinomas. A different pattern was seen in thymic tissues: normal thymus
      had higher telomerase activity than thymomas. The incubation of thymoma extracts
      with normal thymus extracts decreased telomerase activity in the latter. These
      results demonstrate two different patterns of telomerase activity in tumors
      induced by Polyoma virus, and suggest the presence of telomerase inhibitory
      factors in thymomas.

PMID- 9922484
TI  - [Systemic Buschke's scleredema with cardiomyopathy, monoclonal IgG kappa
      gammopathy and amyloidosis. Case report with autopsy].
AB  - A 73 year old retired truck driver and blacksmith was studied in June 1996 for
      thoracic pain and was diagnosed as acute pericarditis which responded well to
      steroid treatment. In January 1997, he noted swelling of the abdominal skin,
      genitalia and limbs, sparing the feet. He was euthyroid, did not have evidence of
      diabetes or a Raynaud's phenomenon. His proteinogram showed an IgG-Kappa
      monoclonal paraprotein M component, 1.31 g/oo. TSH and tetraiodotironine were
      normal; ESR 16 mm in the first hour. As he did not respond to treatment he was
      referred to our hospital in March 1997. On physical examination the most relevant
      findings were a non-pitting edema of the abdomen and lower limbs, sparing the
      feet. An echocardiogram was consistent with an infiltrative cardiomyopathy. Soon
      after his hospitalization his condition worsened suddenly with severe bradicardia
      (28/minute) due to a junctional rhythm and righ bundle branch block. He suffered
      a cardiac arrest and died. The autopsy findings favoured the diagnosis of
      systemic scleredema adultorum of Buschke. Amyloid deposits were also found
      although not abundant, with a similar distribution except in the skin. In this
      article the clinical and autopsy findings are presented in a patient showing
      coexistence of systemic Buschke's scleredema with an infiltrative cardiomyopathy,
      IgG Kappa gammopathy and amyloidosis.

PMID- 9922485
TI  - [Empirical anti-toxoplasma therapy in cerebral AIDS and Chagas disease.
      Presentation of 2 cases, review of the literature and proposal of an algorithm].
AB  - Trypanosoma cruzi is the responsible agent of Chagas disease and is endemic in
      extended areas of South and Central America. There are many previous reports
      indicating that T. cruzi frequently involves the central nervous system in AIDS
      patients. Here, we present two cases illustrating that neurological involvement
      caused by T. cruzi frequently shows a clinical picture similar to that caused by
      Toxoplasma gondil. Since in neurological Chagas disease early treatment has been
      associated with a better outcome and considering that the diagnosis is easily
      reached by the detection of the agent in the cerebrospinal fluid, we propose a
      new algorithm for the management of AIDS patients presenting neurological focal
      lesions in endemic areas for T. cruzi.

PMID- 9922486
TI  - [Spontaneous chagasic peritonitis in a patient with AIDS].
AB  - An AIDS-Chagas association has been extensively reported in the literature
      specially in cardiac and cerebral localizations. A case is presented of a 36 year
      old male patient with a diagnosis of AIDS and positive serology for Chagas, as
      well as chronic hepatopathy and CD4 cell count of 31. While in the hospital he
      developed ascitis which revealed the presence of numerous tripomastigote forms of
      T. cruzi in the ascitic fluid. This clinical presentation of Chagasic
      reactivation has not been reported in the literature.

PMID- 9922487
TI  - [Moderate hyperhomocysteinemia and atherothrombosis].
AB  - Elevated levels of plasma total hornocysteine are now accepted as an independent
      risk factor for premature atherosclerosis. Nutritional, environmental and genetic
      factors may contribute to increase the levels of homocysteine. The exact
      pathogenesis of vascular damage induced by homocysteine is still not completely
      understood. Various mechanisms have been proposed, including a significant
      prooxidative activity, a stimulation of smooth muscle cells proliferation and an
      endothelial dysfunction. Folate, pyridoxine and cyanocobalamin are important
      cofactors for homocysteine metabolism. In most cases, elevated homocysteine can
      be reduced by administration of vitamin supplements. It has not yet been
      demonstrated that reduction in mortality and morbidity can be achieved with these
      regimens. However, food supplementation with folic acid has been recommended for
      treatment or prevention of homocysteine-related disorders in the North American
      population. Appropriate clinical trials are needed to evaluate the effect of
      lowering moderate homocysteine levels on atherosclerosis.

PMID- 9922488
TI  - [Arterial hypertension, cardiomegaly, heart failure and interstitial pulmonary
      images].

PMID- 9922489
TI  - [AIDS and Chagas: the difficulty of globalizing protocols].

PMID- 9922490
TI  - [Sepsis: uncontrolled inflammation or inflammatory dysregulation?].

PMID- 9922491
TI  - [The dilemma of cancer therapy and the oncologist-patient relationship].

PMID- 9922492
TI  - [The dilemma of cancer therapy and the oncologist-patient relationship].

PMID- 9922493
TI  - [Villous and tubulovillous adenomas of the colon and rectum. Results in 30
      patients].
AB  - Colorectal adenomas precede carcinomas as much as they become larger and present
      villous histology. Since colonoscopic polypectomy cannot remove all polyps,
      surgical options include local resection as well as segmental colectomy.
      Significant morbidity and high recurrence rates may occur following individual
      and polyp-related characteristics. This paper focuses the clinical aspects of
      colorectal tubulo-villous adenomas and the results of the surgical treatment.
      PATIENTS AND METHODS: Hospital charts from 30 patients who underwent surgical
      treatment of colorectal tubulovillous adenomas between 1980 and 1997 were
      retrospectively reviewed. RESULTS: Rectal bleeding, urgency and mucus discharge
      were the most frequent clinical findings. Proctologic examination (digital and
      rigid rectosigmoidoscopy) diagnosed the lesion for the majority of cases. Seventy
      per cent of the polyps were in the distal rectum and 60% were larger than 4 cm.
      Transanal resection was the surgical option for one half of the patients and
      segmental colectomy for the other. Fourty-two per cent of the polyps that were
      considered benign as result of preoperative biopsy showed malignant
      transformation when the whole polyp was examined. Recurrence rate was 26.7% and
      6.7% for patients who underwent local resection and segmental colectomy
      respectively. Postoperative complication rate was similar for the two surgical
      groups. CONCLUSIONS: Recurrence may occur frequently after standard local
      resection. Preoperative biopsy examination has no role for the diagnosis of
      malignant transformation. Office proctologic examination diagnoses majority of
      colorectal polyps that may be elected for surgical resection.

PMID- 9922495
TI  - An alternative technique for open laparoscopy.
AB  - Laparoscopic cholecystectomy has become a routine surgical procedure.
      Complications related to use of the laparoscope frequently result from insertion
      of a Veress needle or blind introduction of the primary cannula on its trocar.
      This risk is clearly higher in patients who have undergone previous surgical
      operations. Open insertion with visualisation of abdominal cavity before the
      introduction of the primary cannula reduces the risk of major vascular and
      visceral injury. Nevertheless, open laparoscopy has rarely been adopted mainly
      due to gas leak from the wound and because it is time-consuming. A simple, quick
      and effective technique is described. The authors experience with this technique
      in the last 500 cases has shown that it has no effect on the duration of
      operation, and does not involve a larger skin incision. This technique has been
      associated with no operative difficulty.

PMID- 9922494
TI  - [Antioxidative effect of N2-mercaptopropionylglycine (N2 MPG) in experimental
      acute pancreatitis].
AB  - The N2-Mercaptopropionylglycine (N2-MPG) is a potent antioxidant by inhibiting
      the abnormal production of xantina-oxidase. The aim of this research is to
      analyze the antioxidant capacity of this tiol compound by offering some
      protection to pancreatic tissue in the acute pancreatitis (AP). The induction of
      AP was obtained through two methods: a) supramaximal dose of cerulein; b)
      infusion of 2.5% sodium taurocholate into the biliopancreatic duct of the rat.
      Thirty-six male Wistar rats (220-270 g) were divided into four groups. AP with
      cerulein (Two parenteral doses of 20 micrograms/kg; one hour interval): in two
      groups: GI: nineteen rats previously treated with N2-MPG (100 mg/kg) ten minutes
      before AP. GII (control): seventeen animals which received saline 0.9%. AP with
      taurocholate (0.5 ml into the main biliopancreatic duct): in other two groups:
      GIII: eleven rats previously treated with N2-MPG (100 mg/kg) ten minutes before
      AP. GIV (control): fifteen animals which received saline 0.9%. The albumin
      leakage into the cell interstice as an inflammatory parameter was measured
      through Evans-Blue (EB) colorimetry, that links totally with serum albumin after
      injection into the pancreatic tissue, immediately before induction of AP. The
      rats were sacrificed one hour after. Water tissue content was also measured.
      There was a relevant reduction of EB leakage in GI (344 +/- 27
      micrograms/gtissue) when compared to GII (729 +/- 84 micrograms/gtissue), p <
      0.01, and in GIII (386 +/- 52 micrograms/gtissue) when compared to GIV (543 +/-
      53 micrograms/gtissue), p < 0.05. There was no difference in tissue water content
      between GI (88.2 +/- 0.6%) and GII (87.4 +/- 0.9%), but certainly between GIII
      (77.7 +/- 2.1%) and GIV (82.8 +/- 1.2%), p < 0.05. The amilase levels didn't show
      any difference among the four groups. These results suggest that the use of the
      antioxidant N2-MPG offers a protective action, at least in rats, reducing the
      severity of AP induced by supramaximal dose of cerulein, and even in a more
      severe AP such as produced by sodium taurocholate at 2.5%, although apparently
      not interfering with its pathogenesis. It also strengthens the actual
      participation of free radicals of oxygen in the physiopathology of acute
      pancreatitis.

PMID- 9922496
TI  - Interest of conventional clinical, biochemical and bioimpedance measurements as
      indicators of mortality risk in critical patients.
AB  - Risk assessment is nowadays an essential part of the management of seriously ill
      subjects, and multiple scoring methods are available, based on single or
      preferably multiple determinations. Some of these protocols have been
      successfully used around the world, and they permit the prediction of outcomes in
      different clinical populations. However, many indices are labor-intensive or
      demand an expanded set of biochemical determinations, thus representing an
      economical burden. Aiming to evaluate the prognostic value of ordinary variables
      that are already present in the clinical observation, 50 consecutive patients
      admitted at the intensive care unit were prospectively documented. Methods
      included clinical (age, sex, stay in ICU, FIO2), biochemical (serum albumin,
      hemoglobin, glucose, creatinine, WBC count), and bioimpedance variables
      (resistance, reactance, body impedance coefficient). All these values were
      registered at admission and before discharge or death, and compared with survival
      rate. Initially only WBC count was significantly different in survivors, but
      ongoing documentation revealed that later on, four indices were endowed with
      prognostic impact: serum album, glucose levels, WBC count and FIO2 requirements.
      Organ or function-sustaining procedures were also associated with outcome,
      nominally mechanical ventilation, vasoactive drugs, and enteral/parenteral
      nutrition. Furthermore, patients submitted to two or three of these methods
      exhibited higher mortality than those receiving just one, with even better result
      for those not requiring any. It is concluded that observation of ongoing changes
      in conventional clinical variables available in the clinical chart are a valid
      means of estimating the mortality risk in critical cases.

PMID- 9922497
TI  - [Iron deficiency in female athletes].
AB  - Iron deficiency and anemia have been reported frequently in athletes. In Sao
      Paulo-Brazil among elite athletes overt anemia is uncommon, but our studies
      showed that they were in a borderline anemic state. Sports anemia is used to
      describe both pseudodilutional anemia and the true anemia of athletes. We studied
      12 female young athletes, all with normal hemoglobin. Four athletes had
      laboratory features (serum ferritin, red cell volume, and/or transferrin
      saturation) suggestive of iron deficiency. There are association of high iron
      body stores with cardiac arrhythmia, carotid atherosclerosis, myocardial
      infarction, liver and colorectal cancer but minor iron deficiency may impair the
      physical fitness.

PMID- 9922498
TI  - [Immunohistochemistry diagnosis of fungal infections].
AB  - Because the mycosis incidence has increased a lot with the appearing of AIDS, the
      Immunohistochemistry study among fungus shows the importance of fast methods for
      their identification that have advantage of been a durable method in comparison
      with immunofluorescence and the possibility of making retrospective studies in
      material embedded in paraffin. The Immunohistochemistry reaction with Histoplasma
      capsulatum, Pneumocystis carinii; and Criptococcus neoformans antibodies were
      sensitive, specifics, and intensely positive in all the cases previously
      diagnosed as Histoplasmosis, Pneumocystosis and Cryptococcosis, without cross
      reaction with other fungus; while the anti-Candida albicans antibody showed weak
      positiveness in four Histoplasmosis cases, in one of Paracoccidioidomycosis cases
      and Sporotrichosis case; and the reactions with the antibody anti-P. brasiliensis
      were intensely positive in all the Paracoccidioidomycosis cases and weakly
      positive in two Histoplasmosis and two of the four Candidiasis cases. The
      previous identification of each fungi on tissue sample was made by Grocott
      method. This preliminary study showed that it is necessary to use other kinds of
      antibody and fungus, in order to get more details about the possible occurrence
      of cross-reactions. We suggest the use of new antibodies, with new
      standardizations in order to find the best titles for each reaction and eliminate
      the cross-reactions.

PMID- 9922499
TI  - [Idiopathic facial pain--Part 1: Definition, classification and etiology].
AB  - The present paper introduces a new concept in the physiopathology and treatment
      of the called 'temporomandibular dysfunction'. This paper was divided into two
      parts, this first explaining its definition, aetiology and hypothesis of the
      idiopathic facial pain. The second part, will mention its treatment, prognosis
      and recommendations. Under this new view, this 'dysfunction' is part of the
      called Idiopathic Facial Pain. The idiopathic facial pain is didactically
      subdivided in (1) facial artromialgia, (2) atypical facial pain, (3) atypical
      odontalgia and (4) oral dysestesia. Occlusal factors are less important in its
      aetiology, and psychological and biochemical factors are more recognised. Correct
      diagnosis is essential, and a full history, including psychological and social
      aspects is very important. The present management is based on a working model
      developed in this department and in other world centres, and is revolutionising
      the clinical management of the patients with idiopathic facial pain.

PMID- 9922500
TI  - [Propionic acidemia in the neonatal period].
AB  - Propionic Acidemia is an inherited disorder of organic acid metabolism
      characterized by a wide spectrum of clinical and biochemical findings. Many times
      is present in the neonatal period, when mortality is high and neurologic residua
      in survivors is severe. The present case concerns to a healthy male newborn who
      started with a picture of refusing to feed, lethargy and hypothermia at 49 hours
      of life. He developed a severe neurotoxicity state with metabolic acidosis. The
      laboratory evaluation showed high levels of 3-hidroxi-propionic, 2-metil
      hidroxibutiric and metil-citric in urine, confirming the diagnosis of proprionic
      acidemia.

PMID- 9922501
TI  - [Acute appendicitis following laparoscopic inguinal hernioplasty. Coincidence or
      complication?].
AB  - Intraperitoneal complications related to laparoscopic inguinal hernia repair by
      transabdominal approach had been described. The authors report the first case of
      postoperative acute appendicitis in a patient submitted to a transuretral
      prostate resection and bilateral inguinal hernioplasty by the TAPP technique,
      resulting in a second laparoscopic intervention.

PMID- 9922502
TI  - [Reiter's syndrome and human immunodeficiency virus infection].
AB  - The increase of rheumatic disorders in HIV infected has been known for the last
      decade with special emphasis on Reiter's Syndrome. In spite of common sources of
      HIV and other microorganisms being important in the pathogenesis of Reiter's
      Syndrome, severe immunodeficiency may be important in the development of
      rheumatic diseases, mainly because of the presence of arthritogenic
      microorganisms. The decrease of TCD4 lymphocytes, the increase of TCD8
      lymphocytes and the modification of immune regulation may be important in the
      pathogenesis of Reiter's Syndrome in patients infected by HIV. There is no
      clinical response to nonhormonal anti-inflammatory drugs in the treatment of this
      entity.

PMID- 9922503
TI  - [Muscle-aponeurotic transposition for treatment of anal incontinence].
AB  - The management of anal incontinence varies. It can be treated either clinically
      or surgically depending on its etiology and the intensity of the signs and
      symptoms. The variety of procedures and techniques employed in its treatment is
      proof of the incomprehension of the pathophysiological mechanisms involved as
      well as their diversity. Sphincteroplasties are indicated for those patients with
      well-defined muscle injury, usually resulting from obstetrical trauma, iatrogenic
      surgery or vehicular accidents. In cases of persistent anal incontinence after
      previous sphincteroplasty or those in which extensive destruction of the
      sphincteric musculature is confirmed, muscle-aponeurotic transpositions are an
      attractive option. A detailed survey of the literature of the chief techniques
      utilized and their results is presented.

PMID- 9922504
TI  - [League against pain: a teaching experience].
AB  - The anatomical and physiological basis of pain are subjects of the basic sciences
      in health sciences undergraduate curriculum. Disciplines focussing pain concepts
      and pain therapy are not traditional in the medical and nursing schools programs.
      The description of the organization of the League Against Pain and the
      presentation the students' opinions about their participation in this educational
      program were the objectives of the study. The League is composed by nursing and
      medical students and professionals (physicians of many specialties and nurses).
      The objectives of the League are: the improvement of the teaching about pain
      subjects in the nursing and medical schools; the development of research in
      epidemiological, clinical and therapeutic aspects of pain; the development and
      promotion of a model of multidisciplinary and multiprofessional assistance to
      chronic pain patients. The students considered had improved their abilities in
      pain control and in professional-patients relationship; usefulness and
      satisfaction with the program; need for inclusion of the program in the
      undergraduate courses and that the League is a good model for teaching of medical
      and nursing students in pain.

PMID- 9922505
TI  - [Prevalence and genotypes of hepatitis C virus in blood donors and in patients
      with chronic liver disease and hepatocarcinoma in a Chilean population].
AB  - BACKGROUND: The impact of hepatitis C virus infection in Chile has not been well
      established. AIM: To assess hepatitis C virus infection in normal Chileans and in
      patients with liver disease. SUBJECTS AND METHODS: Antibodies against hepatitis C
      virus were investigated in 21,000 blood donors, 133 patients with non alcoholic
      chronic liver disease and in 50 patients with hepatocarcinoma. Viral RNA was
      studied by polymerase chain reaction in all positive blood donors, in 51 patients
      with chronic liver disease and in all patients with hepatocarcinoma. Hepatitis C
      virus genotype was established using restriction fragment length polymorphism in
      118 RNA positive samples. RESULTS: In blood donors, a 0.3% prevalence of positive
      antibodies was found. The figure for chronic liver disease was 53% and for
      hepatocarcinoma, 48%. Viral RNA was detected in 100% of patients with chronic
      liver disease and hepatocarcinoma and in 68% of blood donors with positive
      antibodies. Genotype 1b was identified in all infected patients with
      hepatocarcinoma, in 86% of patients with chronic liver disease and in 46% of
      blood donors. CONCLUSIONS: Hepatitis C virus infection is an important etiologic
      agent for chronic liver disease in Chile. The predominance of genotype 1b among
      patients with the most severe form of liver disease is in agreement with
      observations made abroad.

PMID- 9922506
TI  - [Interleukin-6 and interferon-gamma release from blood mononuclear cells and
      colonic mucosa from patients with ulcerative colitis].
AB  - BACKGROUND: Cytokines are involved in the pathogenesis of inflammatory bowel
      diseases such as ulcerative colitis and Crohn disease. AIM: To measure cytokine
      release by mononuclear cells of patients with ulcerative colitis. PATIENTS AND
      METHODS: Twelve patients subjected to a diagnostic colonoscopy were studied. Six
      had an ulcerative colitis and six did not have inflammatory changes in the
      colonic mucosa and were considered as control. Mononuclear cells were isolated
      from biopsies of colonic mucosa and from peripheral blood cultivated during 48
      hours with pokeweed mitogen, and Interleukin 6 and interferon-gamma were measured
      in their supernatants. RESULTS: In patients with ulcerative colitis, interleukin
      6 secretion by peripheral blood mononuclear cells was higher than in control
      subjects in the basal period (2212 +/- 424 and 443 +/- 174 pg/ml respectively p =
      0.03) and after stimulation with pokeweed mitogen (16,328 +/- 1275 and 5462 +/-
      322 pg/ml respectively p = 0.03). No differences in interleukin 6 secretion by
      colonic mucosa mononuclear cells were observed. Unstimulated cells did not
      liberate interferon-gamma. The secretion of this lymphokine by stimulated colonic
      mucosa cells was lower in patients with ulcerative colitis than in controls (1571
      +/- 216 and 7953 +/- 389 pg/ml respectively p = 0.03). CONCLUSIONS: Local and
      systemic changes in interleukin 6 and interferon-gamma secretion occur in
      patients with ulcerative colitis. These changes could be related to the
      development of the disease.

PMID- 9922507
TI  - [Polycystic ovary syndrome: relationship of insulin tissular sensitivity, LH
      secretion and ovarian morphophysiologic changes].
AB  - BACKGROUND: Insulin resistance to LH hypersecretion are recognized features of
      polycystic ovary syndrome. Previous studies have suggested that both defects are
      independent from each other. AIM: To examine the relationship between insulin
      sensitivity and LH secretion in women with polycystic ovary syndrome. PATIENTS
      AND METHODS: Eighteen women with clinical and biochemical evidence of
      hyperandrogenism, normal oral glucose tolerance test and polycystic ovaries on
      ultrasonography, were studied. Insulin sensitivity was assessed using the insulin
      tolerance test. LH secretion was studied integrating LH values of blood samples
      taken every 10 minutes for 6 h. Testosterone, testosterone index, SHBG and IGFBP
      1 were measured in three selected samples and ovarian volume was assessed by
      ultrasound. RESULTS: Insulin sensitivity ranged from 0.06 to 0.75 and the area
      under the curve for LH, from 532 to 8.517 IU/L/6 h. No correlation was found
      between these two parameters and between each parameter and ovarian volume or
      androgen concentration. Positive correlations were observed between insulin
      sensitivity and SHBG concentrations (r = 0.612 p < 0.01) and IGFBP-1
      concentrations (r = 0.588 p < 0.001). When compared to patients body mass index
      of less than 30 kg/m2, patients with body mass index over 30 kg/m2 had
      significantly lower insulin sensitivity and higher LH levels. In the latter a
      positive correlation between insulin sensitivity and the area under the curve for
      LH was observed (r = 0.683 p < 0.02). CONCLUSIONS: Obese polycystic ovary
      syndrome patients exhibited an inverse correlation between insulin resistance and
      LH hypersecretion, suggesting a relationship between both defects.

PMID- 9922508
TI  - [Effect of maternal smoking on offspring growth].
AB  - BACKGROUND: Maternal smoking negatively affects birth weight, breast milk volume
      and growth at one month of age. AIM: To study the effect of maternal smoking on
      the growth of three month old infants. SUBJECTS AND METHODS: Ten smoking and 10
      non smoking mothers with one month old children, under exclusive breast feeding,
      were selected for the study. Urinary cotinine levels in the mothers and children
      were measured to assess smoking. Two months later, children were reassessed.
      RESULTS: Smoking mothers consumed a mean of 6.5 cigarettes/day. Compared to non
      smokers, urinary cotinine levels were higher in these mothers (60 +/- 21 and 1428
      +/- 716 ng/ml respectively, p < 0.001) and their offspring (21 +/- 20 and 156 +/-
      101 ng/ml respectively p < 0.001). Compared with smokers, at three months of age,
      children of non smoking mothers had a higher average weight (5829 +/- 498 and
      6325 +/- 427 g, p < 0.02). CONCLUSIONS: Measurement of urinary cotinine levels is
      a reliable and objective measure of maternal smoking and nicotine transfer to the
      offspring. It also allows the assessment of passive smoking. Maternal smoking
      adversely affects child growth at three months of age.

PMID- 9922509
TI  - [Protein diffusion patterns in human saliva].
AB  - BACKGROUND: There are two modes of saliva protein diffusion on a cellulose flat
      matrix. The monophasic mode of diffusion consists in a homogeneous distribution
      of salivary protein components on the matrix. On the contrary, in the biphasic
      mode, an area occupied by nondiffusible proteins is surrounded by an area
      occupied by diffusible proteins. AIM: To study protein diffusion patterns of
      saliva obtained from normal human volunteers. MATERIAL AND METHODS: Saliva was
      obtained from 33 subjects aged 67.5 +/- 12 years old (29 female). Forty
      microliters of saliva were deposited in the center of cellulose disks for protein
      diffusion assays. RESULTS: Thirty three whole saliva samples and 31
      submandibular/sublingual samples showed a biphasic diffusion pattern. On the
      contrary, 62 out of 66 samples of parotid saliva displayed a monophasic diffusion
      pattern. In one parotid saliva samples and 2 submandibular/sublingual samples,
      the diffusion pattern could not be established. Patterns of salivary protein
      diffusion were highly consistent within the same individual. Eighty percent of
      subjects had an unequivocal pattern of saliva protein diffusion. CONCLUSIONS: The
      monophasic mode of saliva protein diffusion is a feature of parotid saliva,
      whereas the biphasic mode is characteristic of submandibular/sublingual and whole
      saliva.

PMID- 9922510
TI  - [Lipids, lipoproteins and apolipoproteins in normal newborns].
AB  - BACKGROUND: In Chile, there is a high prevalence of cardiovascular diseases.
      Because atherosclerosis starts in childhood, it is important to assess serum
      lipid levels in children. AIM: To measure serum lipid levels in normal Chilean
      newborns. SUBJECTS AND METHODS: A sample of umbilical cord venous blood was
      obtained from 156 normal newborns (76 male) immediately after delivery. Total and
      HDL cholesterol, triglycerides, apoprotein A1, B and lipoprotein (a) were
      measured. RESULTS: Mean values for total cholesterol in males, females and in the
      total sample were 60.6, 67.8 and 64 mg/dl respectively. The figures for HDL
      cholesterol were 24.9, 29.3 and 27 mg/dl, for LDL cholesterol were 28.3, 32.4 and
      30 mg/dl, for triglycerides were 37.5, 30.3 and 35 mg/dl, for apoprotein A1 were
      69, 79 and 74 mg/dl, for apoB were 23, 25 and 24 mg/dl and for lipoprotein (a)
      were 1.58, 1.79 and 1.69 mg/dl. Total cholesterol, HDL cholesterol, triglycerides
      and apoprotein A1 were significantly different between sexes. Percentiles 5 and
      95 for total cholesterol were 37 and 111, for HDL cholesterol were 14 and 40, for
      LDL cholesterol were 13 and 57, for triglycerides were 20 and 69, for apoprotein
      A1 were 53 and 101, for apoprotein B were 11 and 48 and for lipoprotein (a) were
      1.3 and 2.1 mg/dl. Five percent of children had apoprotein B values over 48
      mg/dl. CONCLUSIONS: The detection of high levels of apoprotein B in newborns,
      could allow the early identification of individuals with high cardiovascular
      risk.

PMID- 9922511
TI  - [Surface characteristics and antimicrobial sensitivity of clinical strains of
      Acinetobacter spp].
AB  - BACKGROUND: The treatment of nosocomial infections caused by Acinetobacter
      baumannii has been hindered by the easiness of this species to acquire
      antimicrobial resistance. AIM: To study surface hydrophobicity, the presence of
      capsule and antimicrobial susceptibility of nosocomial Acinetobacter spp strains.
      MATERIAL AND METHODS: Ninety four Acinetobacter spp strains isolated from a
      public hospital of Santiago, between July 1995 and April 1996, were studied.
      RESULTS: Compared to Acinetobacter genospecies 3 isolates, A baumannii isolates
      exhibited greater antimicrobial resistance, was uniformly susceptible to imipenem
      and highly resistant to other antimicrobials of clinical use. Most strains of
      biotypes 8 and 9 were hydrophilic and encapsulated, whereas those of infrequent
      biotypes and of Acinetobacter genospecies 3 were, with few exceptions,
      hydrophobic and not encapsulated. CONCLUSIONS: Capsule production might confer a
      greater virulence to Acinetobacter baumannii biotypes 8 and 9, and explain their
      higher prevalence in the studied hospital.

PMID- 9922512
TI  - [Eating disorders in adolescents: clinical and epidemiological aspects].
AB  - OBJECTIVE: To compare in female adolescents clinical and epidemiological aspects
      of eating disorders. METHODS: Three hundred schoolgirls, university students and
      young girls with weight problems who did not score within the pathological range
      of the Eating attitudes test (EAT-40) (group S), one hundred and thirty eight
      schoolgirls, university students and young girls with weight problems who scored
      within the pathological range of the EAT-40 (group SC) and one hundred eating
      disordered patients (group THC) were given the Eating disorders inventory (EDI).
      RESULTS: The EAT-26 emerged as an abbreviated and trustful instrument. The scores
      on the EAT-40 and EDI were lower in group S, intermedial in group SC and higher
      in group THC. The same statistically significant differences (p < 0.001) were
      observed on Interoceptive awareness. Bulimia, Ineffectiveness and Maturity fears.
      Diet (EAT-40-Factor I) (90%) and EDI-Drive for thinness (87%) had the highest
      sensitivity. CONCLUSIONS: The EAT-26, EAT-40 and EDI were useful to confirm an
      eating disorder. On one hand, the profile of the eating disordered patients and
      the adolescents at risk was characterized by a high Drive for thinness and Body
      dissatisfaction and on the other, by a low Interoceptive awareness. Diet and
      Drive for thinness may be helpful for screening large non-clinical groups to
      predict an eating disorder. Finally, the importance of the nutrition assessment
      and primary prevention is emphasized.

PMID- 9922514
TI  - [Collagenous sprue. Clinical case].
AB  - A 47 years old female, treated in 1984 for a non Hodgkin lymphoma, presented in
      1993 with diarrhea with features of steatorrhea. The initial assessment concluded
      that the patient had a gluten induced enteropathy and she had a good clinical
      response to a gluten free diet. In 1996, while still on gluten free diet,
      steatorrhea appeared. A new intestinal biopsy showed sub epithelial collagen
      deposition. After an empiric treatment with prednisone and sulphasalazine,
      steatorrhea abated but subepithelial collagen deposition persisted in intestinal
      biopsies.

PMID- 9922513
TI  - [Results of the National Protocol for Antineoplastic Drugs in the treatment of
      adult acute lymphoblastic leukemia. Experience at the Hospital del Salvador, 1990
      1997].
AB  - BACKGROUND: Acute lymphoblastic leukemia has a different evolution in children
      and adults. Complete remission is achieved in 70-85% of the latter, but only 25
      to 35% have a prolonged disease-free survival. AIM: To assess the treatment
      outcome of adults with acute lymphoblastic leukemia in Chile. PATIENTS AND
      METHODS: A retrospective review of the medical files of 51 adults with acute
      lymphoblastic leukemia treated according to the national protocol for
      antineoplastic drugs, in a public hospital of Santiago. RESULTS: Mean age of
      patients was 35.9 years old and 53% were younger than 20 years old. Complete
      remission was achieved in 64%. Early mortality occurred in 22%, mostly due to
      infections. Treatment failure occurred in 16%. Global survival was 17 months and
      global survival at 5 years was 24%. Prognostic criteria of the protocol, defined
      a low risk group that had a complete remission of 100%, no early deaths and 5
      year disease-free survival of 53%. The group defined as having high risk had a
      complete remission of 47%, a 29% early mortality and a 5 years disease-free
      survival of 6%. CONCLUSIONS: Aiming to improve treatment results in acute
      lymphoblastic leukemia, efforts should be made to improve the management of
      febrile neutropenic patients and to intensify chemotherapy.

PMID- 9922515
TI  - [Cushing with transition from pituitary to adrenal origin. Study with SPECT
      scintigraphy of the adrenal cortex with norcholesterol-I 131 in a case].
AB  - The case of a 49 yr old alcoholic women with clinical and laboratory findings
      that suggested a Cushing syndrome is presented. The functional tests showed
      cortisol suppression greater than 50% of the basal value with 8 mg of
      dexamethasone and no response in the combined dexamethasone/desmopressin test.
      Pituitary Nuclear Magnetic Resonance (NMR) was negative, Abdominal Computed Axial
      Tomography suggested hyperplastic adrenal glands; adrenal nodules were not found
      in the NMR. Pituitary or hipothalamic Cushing with secondary autonomous
      micronodular adrenal hyperplasia was suspected. Norcholesterol-I131 SPECT
      scintigraphy under dexamethasone suppression demonstrated a functional adrenal
      hyperplasia which was hystologically confirmed.

PMID- 9922516
TI  - [Immune modulating effect of intravenous gamma globulin in a patient with
      overlapping syndrome].
AB  - We report a 46 years old woman with a diagnosis of systemic lupus erythematosus
      and scleroderma overlapping syndrome. During treatment with steroids and
      azathioprine, the appearance of paresthesias and a progressive invalidating
      proximal weakness was interpreted as a steroidal myopathy. Steroidal treatment
      was progressively discontinued, but lupic activity and esophageal involvement
      exacerbated. Therefore, the use of immune modulating doses of intravenous gamma
      globulin (2 g/kg/total dose) was decided. The patient received this dose in two
      consecutive days and, 48 hours later, a notable improvement in esophageal
      function and general condition was verified. After six months of follow up, the
      disease remains inactive.

PMID- 9922517
TI  - [Cardiovascular manifestations of obstructive sleep apnea. Effects of the
      treatment].
AB  - There is a direct relationship between obstructive sleep apnea and high blood
      pressure, ischemic heart disease and cerebrovascular disorders. Obstructive sleep
      apnea, defined as an intermittent complete or partial upper airway obstruction
      during sleep, occurs in approximately 4% of adults, although some authors suggest
      a 9% prevalence in women and 24% in men. Due to its high frequency, this
      condition must be considered as another cardiovascular risk factor that should be
      prevented and adequately treated.

PMID- 9922518
TI  - [Severe ovarian hyperstimulation syndrome: an intensive care disease].
AB  - Ovarian hyperstimulation syndrome is a severe and potentially fatal iatrogenic
      disease that affects 2% of women subjected to pharmacological induction of
      ovulation. The newest data on the clinical picture, risk factors, pathophysiology
      and management of this disease, are reviewed.

PMID- 9922519
TI  - [Comparative study of the efficacy of two types of BCG vaccines administered in
      different doses].
AB  - BACKGROUND: In 1993, WHO and UNICEF recommended the administration of 0.05 ml
      doses of BCG, instead of 0.1 ml, to newborns. This recommendation was adopted by
      the Chilean Ministry of Health, using the Merieux vaccine. Subsequently,
      different Health Services detected a high percentage of children without BCG scar
      at the time of their growth and development control. AIM: To assess the efficacy
      of BCG vaccination in a double blind randomized fashion, using two vaccine types
      and different doses. PATIENTS AND METHODS: Newborns of two public hospitals of
      Santiago were randomly assigned to receive the Tokio or Merieux BCG strains in
      doses of 0.05 or 0.1 ml. Ninety five to 125 days after vaccination, vaccine scar
      was measured and inmunogenicity was assessed using the tuberculin test. RESULTS:
      Six hundred newborns (150 in each group) were included in the protocol and
      results were assessed in 408. The percentage of children with a PPD reaction of 0
      mm was 9.3, 3.7, 7.8 and 0% with the Merieux vaccine in doses of 0.1 ml, Tokio
      vaccines in doses of 0.1 ml, Merieux vaccine in doses of 0.05 ml and Tokio
      vaccine in doses of 0.05 ml, respectively. In the same groups the scar diameters
      were 6.4 +/- 3.4, 7.3 +/- 2.7, 5.6 +/- 2.8 and 7.3 +/- 2.9 mm. The observed
      differences for each group are significant, depending on the type of strain and
      dose, but favoring the Tokio type of vaccine. CONCLUSIONS: The BCG scar diameters
      obtained in this study are similar to those obtained in previous works in 1984
      and 1986. This scar is the evidence of vaccination that nurses detect in health
      controls. Therefore the use of 0.1 doses for vaccination, that result in better
      scars and PPD response, is recommended.

PMID- 9922520
TI  - [Biomedical articles by Chilean authors published in international journals in
      1997. A review from MEDLINE].

PMID- 9922521
TI  - [Hepatitis G infection in Chilean patients with hepatitis C virus: a preliminary
      report].

PMID- 9922522
TI  - [History of the Belgian Society of Orthopedic Surgery and Traumatology].

PMID- 9922523
TI  - [History of Acta Orthopaedica Belgica (AOB)].

PMID- 9922524
TI  - [Surgical treatment of fractures and pseudarthrosis prior to Lambotte].

PMID- 9922526
TI  - [Education, formation, verification of knowledge].

PMID- 9922525
TI  - [Reflections on biomechanics].

PMID- 9922527
TI  - [Reflections on the actual state of traumatology of the locomotor apparatus in
      Belgium].

PMID- 9922528
TI  - [Influence of muscular degeneration of the supra- and infra-spinatus on the
      prognosis of surgical repair of the rotator cuff].

PMID- 9922529
TI  - Primary glenohumeral osteoarthritis: clinical and radiographic classification.
      The Aequalis Group.
AB  - One hundred and fifty-one cases of primary glenohumeral osteoarthritis were
      analyzed both clinically and radiographically with CT scanning. There were 76%
      females in this series, and the mean age at operation was 66.8 years. The
      diagnosis was made only with true anteroposterior views of the shoulder which
      show the narrowing of the glenohumeral joint and the presence of osteophytes. The
      arthrogram showed a supra-spinatus tear in 10% of the cases that extended to the
      infra-spinatus in 2.6%. Glenoid retroversion averaged 15.4 degrees. However,
      measurements of glenoid retroversion with CT-scan do not distinguish posterior
      wear from glenoid dysplasia. Posterior subluxation of the humeral head was
      observed in 45% of the cases. We describe a classification of the glenoid
      morphology in three types: Type A (53.5%) is characterized by an equal balance of
      forces acting on the glenoid and a centralized humeral head. Type B (39.5%) has
      asymmetrical posterior force distribution on the glenoid and a posterior
      subluxation of the humeral head. Type C (5%) is arbitrarily defined as glenoid
      retroversion greater than 25 degrees. Posterior subluxation of the proximal
      humeral head did not correlate with either glenoid retroversion or humeral
      retroversion. However, subluxation of the humeral head may be responsible for the
      posterior glenoid erosion and possibly for the biconcave appearance of the
      glenoid observed in primary glenohumeral osteoarthritis. The posterior
      subluxation of the humeral head may still be present after shoulder arthroplasty
      and may be responsible for glenoid loosening due to a "horizontal rocking-horse
      effect".

PMID- 9922530
TI  - [Surgery for lumbago and fibromyalgia].

PMID- 9922531
TI  - [Philosophy of total hip replacement].

PMID- 9922532
TI  - The role of longitudinal tibial rotation in the replaced knee.

PMID- 9922533
TI  - Viable meniscal transplantation.

PMID- 9922534
TI  - [Clubfoot equinovarus: look at the real world].

PMID- 9922535
TI  - [Thoracolumbar fractures. Pathomorphology and indications for treatment].
AB  - The indications for conservative and surgical management of fractures of the
      thoracolumbar spine are reviewed, based upon the morphology of the lesions, which
      is assessed by meticulous analysis of radiographs, CT scan and in some cases MRI.
      The author advocates using the AO classification, which considers several
      subtypes of fractures: compression fractures, distraction fractures and fractures
      with multidirectional displacement. The indication for treatment is based upon
      morphological analysis of the lesions, while other factors such as the general
      condition of the patient or the locally available surgical environment must also
      be taken into consideration. Up to 50% of thoracolumbar fractures can benefit
      from surgical management, with posterior or anterior stabilisation, the latter
      performed through thorascoscopy in selected cases.

PMID- 9922536
TI  - Effect of forearm rotation on grip strength.
AB  - Forearm rotation affects grip strength. In a study with 40 volunteers, an overall
      decrease in grip strength was observed when the forearm rotated from pronation to
      supination. In males grip strength in pronation was significantly lower compared
      to the neutral and supinated position, with the wrist free as well as in an
      immobilized wrist position. In females this was only observed with a free wrist
      position, but with the wrist immobilized, the grip strength was higher in
      supination compared to neutral and pronation.

PMID- 9922537
TI  - Surgical treatment of trigger fingers.
AB  - The surgical treatment of 55 trigger fingers resulted in 87% patient
      satisfaction, without major complications. The mean incapacity was 1.4 weeks.
      Three recurrences were noted; four patients had a slight extension lag and three
      still experienced some local pain.

PMID- 9922538
TI  - Clinical validity of the elbow flexion test for the diagnosis of ulnar nerve
      compression at the cubital tunnel.
AB  - We evaluated the elbow flexion test in 216 elbows without compression of the
      ulnar nerve at the cubital tunnel and without other neuropathies. We used Rayan's
      four positions as our test. The percentage of positive tests was only 3.6% at one
      minute, whereas evaluating the responses at three minutes we saw positive results
      in 16.2%. Therefore we find that if the test is performed for one minute it may
      be useful to help in diagnosing ulnar nerve compression at the cubital tunnel.

PMID- 9922539
TI  - Psychological distress deteriorates the subjective outcome of lumbosacral fusion.
      A prospective study.
AB  - A prospective study was set up to evaluate the influence of psychological
      distress on the outcome of lumbosacral fusion in a group of chronic low back pain
      (CLBP) patients. Response to low back surgical procedures depends upon physical
      and psychological factors. Various reports exist concerning the influence of a
      patient's psychological condition on the outcome of low back surgery. Few
      investigators, however, have checked this influence in a prospective manner. A
      psychogenic back pain score (NPL) was administered to 53 CLBP patients (24 men
      and 29 women) prior to surgery, to evaluate the presence of psychological
      distress. According to the test score patients were divided in an "organic", an
      "uncertain" and a "psychogenic" group. Disability in activities of daily living
      resulting from the back pain was also scored preoperatively with the Oswestry
      Disability Index (ODI). Twelve months after surgery the ODI was readministered to
      the 50 patients available to follow-up. Each group separately showed significant
      improvement of disability 12 months after fusion, however, the "organic" group
      scored significantly better than the "psychogenic" group. Questionnaires about
      back pain, sciatic pain and use of analgesics and Visual Analog Scales regarding
      pain and disability also indicated better results in the "organic" group.
      Psychological distress deteriorates the subjective outcome of lumbosacral spine
      fusion and psychological screening should indeed be an integral part of the
      global assessment of CLBP patients, especially when surgery is considered.

PMID- 9922540
TI  - Acute ulnar collateral ligament injuries of the thumb metacarpophalangeal joint:
      an anatomical and clinical study.
AB  - Treatment of acute injuries of the ulnar collateral ligament of the
      metacarpophalangeal joint of the thumb remains controversial owing to the
      difficulty involved in establishing an accurate diagnosis. Conservative treatment
      may be successful in sprains, but surgical repair has been advocated when the
      ligament is completely torn. The authors performed a comparative study of the
      anatomical lesions of the metacarpophalangeal joint of the thumb with respect to
      degrees of instability. The study was conducted on fresh specimens and
      retrospectively in surgically treated patients. Instabilities greater than 30
      degrees were found to correspond to complete rupture of the ulnar collateral
      ligament of the metacarpophalangeal joint of the thumb, and the stump of the
      ligament was found on the adductor aponeurosis in 5 out of 20 cases. In 2 out of
      9 cases of avulsion-fractures, the fragments were rotated 90 degrees although on
      x-rays they appeared slightly displaced. It is concluded that surgical repair is
      the treatment of choice for instabilities greater than 30 degrees and for
      avulsion-fractures.

PMID- 9922541
TI  - The femoral supracondylar nail: preliminary experience.
AB  - The treatment of supracondylar fractures of the femur with an intramedullary nail
      presents some theoretical advantages. Compared to plate osteosynthesis,
      intramedullary fixation requires less extensive dissection and is biomechanically
      more favorable. In the elderly patient, these characteristics seem important
      since bone quality, extensive procedures and bone grafting remain problematic.
      Since August 1994 we have treated 16 consecutive closed fractures of the distal
      femur (A.O. type: 7 A.1, 2 A.3, 4 C.1, and 3 C.2) with the Green-Seligson-Henry
      intramedullary retrograde supracondylar nail. Twelve elderly and osteoporotic
      patients had suffered low-energy trauma, three young patients had been involved
      in a traffic accident and one other young patient had attempted suicide. The
      operative technique, complications and results are described. All fractures
      healed within a few months (2 to 7) without bone grafting. No failure of the
      fixation material and no deep infection were encountered. With most elderly
      patients the functional result was judged satisfactory, considering the
      population studied. Intraoperative determination of alignment and avoiding
      shortening were the major difficulties, especially with long oblique or
      comminuted fractures. Two major complications were encountered in the young
      population. In one instance nail protrusion in the intercondylar notch caused a
      deep patellar cartilage erosion and sympathetic distrophy leading to a 15 degrees
      flexion deformity. Another young patient needed a quadriceps release at the
      fracture site and subsequently a femoral valgus osteotomy in order to achieve an
      acceptable final result. In elderly osteoporotic patients presenting an isolated
      supracondylar fracture, antegrade nailing remains the "safest" technique by
      avoiding an unnecessary arthrotomy. When previous hip or knee surgery precludes
      the use of antegrade nailing techniques or when the fracture extends into the
      intercondylar region, retrograde supracondylar nailing offers some advantages
      compared to conservative treatment or plate osteosynthesis. On the other hand in
      young patients, anatomic reduction and alignment should be the goal, and open
      reduction with plate osteosynthesis, supplemented by bone grafting if needed,
      should remain the gold standard. When this seems technically impossible, the
      antegrade or retrograde insertion of an intramedullary nail with intraoperative
      assessment of length and fracture alignment is an interesting alternative.

PMID- 9922542
TI  - Patellofemoral pain syndrome in athletes: a 5.7-year retrospective follow-up
      study of 250 athletes.
AB  - Two hundred fifty athletes from a sports clinic, 122 (49%) females and 128 (51%)
      males (mean age 21.1 years), who were diagnosed as having patellofemoral pain
      syndrome (PFPS) and were instructed to practice vastus medialis training,
      returned a completed questionnaire after an average of 5.7 years' follow-up.
      Sixty-eight (27%) were pain-free for an average of 8.1 months: 17 (25%) women and
      51 (75%) men. As to the remaining 182 (73%) who were still suffering, 95 (52%)
      had experienced a decrease in pain, 64 (35%) were unchanged and 23 (13%) had
      experienced an increase in pain. Sixty-eight (37%) described the pain as being
      mild, 88 (48%) as moderate, and 26 (15%) as severe. Athletic activity was
      affected in 184 (74%) of the cases, employment in 16 (6%) cases. The prognosis
      was not correlated with a history of trauma or with age. Athletes with a
      hypermobile patella had a less good prognosis (r = 0.23, p = 0.04). For about
      half of the athletes the prognosis was good, although the other half obtained an
      inadequate result, using a self-training program.

PMID- 9922543
TI  - Arthroplasty of the forefoot in rheumatoid arthritis: long-term results after
      Clayton procedure.
AB  - The present study aims to evaluate long-term results after Clayton resection
      arthroplasty in patients with symptomatic arthritis of the forefeet. From 1970 to
      1995, 109 patients with a total of 184 rheumatoid forefeet underwent Clayton's
      procedure at an average age of 60 years. Forty-seven of them returned with 82
      operated feet for follow-up by means of patient history, physical examination and
      radiograph an average of 12.8 years later. Overall outcome was judged as
      successful in 60 of the 82 cases with complete pain relief, remarkably improved
      gait capacity and use of normal shoes. Sixteen of the feet were definitely
      improved, but slight to moderate pain, inadequate balance and contact with the
      ground, limited walking distance and use of large shoes were signs of decreased
      operation success. The remaining 5 feet showed recurrent splay-foot deformity
      with intolerable pain, functional disability and restricted gait capacity even
      though specially made surgical shoes were used. The Clayton procedure appears to
      be a suitable method for surgical correction of symptomatic rheumatoid forefeet.

PMID- 9922544
TI  - Nontraumatic bilateral first rib fractures.
AB  - The authors report the case of a 21-year old woman who presented bilateral
      spontaneous fractures of the first ribs, in the posterior portion on the right
      side, in the anterior portion on the left side. The pathogenesis of spontaneous
      fractures of the first rib is discussed.

PMID- 9922545
TI  - [Traumatic ruptures of the peroneal tendons treated by free autologous tendon
      graft].
AB  - The authors report a case of traumatic rupture of both peroneal tendons following
      a varus injury of the ankle. The lesion was diagnosed late and was successfully
      treated by a free autologous tendon graft using the distal end of the peroneus
      brevis tendon to restore the peroneus longus, which was also reinforced by a
      plantaris tendon graft. The authors stress the interest of suspecting the lesion
      after acute varus trauma and in cases of chronic instability of the ankle.

PMID- 9922546
TI  - [Isolated traumatic anterior dislocation of the radial head].
AB  - The authors report 2 cases of isolated traumatic anterior dislocation of the
      radial head in children. In the first case, with an acute dislocation, closed
      reduction followed by plaster cast immobilisation for one month gave a good
      result. In the second case, the dislocation was also traumatic in origin but had
      remained unreduced for 5 years. Arthrography of the elbow showed the head to be
      intracapsular. The authors believe that a neocapsule forms in cases of old
      unreduced dislocation and arthrography is therefore of little help to
      differentiate a long standing traumatic dislocation from a congenital
      dislocation. Based on their experience and on the literature, the authors propose
      closed reduction followed by immobilisation as a treatment for acute dislocation;
      old unreduced dislocations cannot be reduced by manipulation and with the
      exception of very symptomatic cases, the authors prefer to avoid open reduction,
      which carries a risk of joint stiffness.

PMID- 9922547
TI  - Fracture of the ossified Achilles tendon.
AB  - The authors report a fracture of an ossified Achilles tendon in a 44-year-old
      male patient who was admitted to the hospital after a minor injury with pain on
      the posterior aspect of his left calf. Examination disclosed a fracture of the
      ossified Achilles tendon. Plain roentgenogram and MRI confirmed Achilles tendon
      ossification and fracture at the distal one-third of the tendon. Surgical
      treatment with excision of the ossified mass and reconstruction with an Achilles
      tendon flap was performed. After two years, the patient has quite good function,
      and MRI shows healing of the tendon.

PMID- 9922548
TI  - [Anterior cruciate ligament prosthesis. Analysis of a failure].
AB  - Prosthetic ligaments of the knee have been very popular in the eighties. It took
      a number of years to become aware of the fact they are unable to provide long
      term stability to the knee joint. This report reviews the development of these
      prostheses, and tries to analyze the reasons for their failure and to find out
      why it took such a long time to demonstrate this failure, in order to draw a
      lesson from the past.

PMID- 9922549
TI  - Frozen shoulder--an algoneurodystrophic process?
AB  - The frozen shoulder syndrome and the Sudeck syndrome are clinically in many
      aspects similar. Radioisotope bone scan shows an increased uptake in the affected
      areas in both diseases, while standard radiographs show a progressive
      demineralization. With measurement of bone-mineral density by quantitative
      digital radiography these local decalcification processes were diagnosed in an
      early stage of the frozen shoulder syndrome: of 12 patients with primary frozen
      shoulder 10 had a bone-mineral density decrease of more than 21% in the humeral
      head of the affected shoulder compared to the unaffected side. In the control
      groups (n = 32) the difference between affected and unaffected side (left and
      right humerus of the healthy probands) was in only one case each above 21%. There
      are several indications in the literature assuming the frozen shoulder to be an
      algoneurodystrophic process. Our observation supports this hypothesis, and may
      possibly lead to earlier diagnosis and improved therapeutic management.

PMID- 9922550
TI  - Neurogenic inflammation and reflex sympathetic dystrophy (in vivo and in vitro
      assessment in an experimental model).
AB  - In the chronic constriction injury (CCI) model, signs and symptoms similar to
      those observed in reflex sympathetic dystrophy (RSD) can be induced by loosely
      ligating a rat sciatic nerve. Skin microcirculatory (inflammation-like) disorders
      may result from release of vasoactive neuropeptides at peripheral endings of
      antidromically acting nociceptive nerve fibers. These antidromic mechanisms may
      account for vasodilation and polymorphonuclear leukocyte (PMN) accumulation in
      the ligated hindpaw. We assessed skin blood flow (SBF) on the ligated side, by
      means of laser Doppler flowmetry, before as well as at day 4 after ligation.
      Postligation SBF measurements were performed before and after selective
      (capsaicin) conduction blockade of the ligated sciatic nerve. The extent of PMN
      accumulation was determined by measuring myeloperoxidase (MPO) activity in muscle
      biopsies obtained from the ligated and contralateral nonligated side. As compared
      to preligation SBF values, we observed an increase at day 4. SBF returned to
      preligation values consequent to capsaicin application. MPO activity, when
      compared to the nonligated side, was higher in biopsies obtained from the ligated
      side. These findings indicate that in the CCI-model, antidromically acting C
      nociceptor nerve fibres increase SBF at 4 days after ligation. In addition, these
      antidromic mechanisms may induce an inflammatory response in the ipsilateral
      hindpaw, mediated by release of neuropeptides from the peripheral endings of
      antidromically acting C-nociceptor nerve fibers. This inflammatory response may
      account for various signs and symptoms as observed in the CCI model and may
      mirror pathophysiological mechanisms of RSD.

PMID- 9922551
TI  - Role of neuropeptides in pathogenesis of reflex sympathetic dystrophy.
AB  - In 1993, a study was undertaken at the Hand Clinics of Loyola University Medical
      Center in Chicago to investigate the role of the neuropeptides in the
      pathogenesis of Reflex Sympathetic Dystrophy. All of the patients had recurrent
      or continuous pain, swelling, and stiffness of one or both extremities following
      either acute trauma or surgical intervention. All of the patients showed a
      markedly increased level of bradykinin as well as calcitonin gene-related
      peptide. The levels of bradykinin were four times as high as the controls. A few
      showed increased levels of the other neuropeptides. With these results, we agree
      with Veldman, Goris and others who consider Reflex Sympathetic Dystrophy to be an
      exaggerated regional inflammatory disorder.

PMID- 9922552
TI  - Results of the treatment of posttraumatic reflex sympathetic dystrophy of the
      upper extremity with regional intravenous blocks of methylprednisolone and
      lidocaine.
AB  - The results of the treatment of 36 patients with posttraumatic reflex sympathetic
      dystrophy of the upper extremity with regional intravenous blocks of
      methylprednisolone and lidocaine are presented. The extremity is exsanguinated
      and a tourniquet is applied. A solution of methylprednisolone, lidocaine and
      heparin is injected. The duration of the block is 20-25 minutes. After the limb
      is anesthetized the affected joints can be manipulated in a progressive,
      controlled fashion. With a 1-year follow-up the response to treatment in 25
      patients (69%) was considered as good (relief of spontaneous pain, no limitation
      in finger movement), in 8 as moderate (22%) and in 3 as poor (9%--the symptoms
      were unaltered or worse). Physiotherapy was applied in all patients (program of
      finger exercises, whirlpool therapy). Complications in 2 cases were transient
      superficial thrombophlebitis of the forearm; in 2 other patients the block was
      interrupted because of severe pain in the limb. We found this method simple, easy
      to perform, safe and inexpensive; the results are comparable to other established
      methods of the treatment i.e. sympathetic blocks or calcitonin.

PMID- 9922553
TI  - A cognitive behavioural theory of anorexia nervosa.
AB  - A cognitive behavioural theory of the maintenance of anorexia nervosa is
      proposed. It is argued that an extreme need to control eating is the central
      feature of the disorder, and that in Western societies a tendency to judge self
      worth in terms of shape and weight is superimposed on this need for self-control.
      The theory represents a synthesis and extension of existing accounts. It is
      'new', not so much because of its content, but because of its exclusive focus on
      maintenance, its organisational structure and its level of specification. It is
      suggested that the theory has important implications for treatment.

PMID- 9922554
TI  - The nature of the depressive experience in analogue and clinically depressed
      samples.
AB  - The use of university students as analogue subjects in depression research
      remains a controversial one, because it is not clear if the depressive experience
      of analogue and clinical samples differs qualitatively or quantitatively.
      Accordingly, this study directly compared 101 adult outpatients with major
      depressive disorder to 175 analogue depressed university students on self-report
      severity ratings of DSM-IV symptoms of major depressive episode. Several goodness
      of-fit indices revealed that the covariance matrices of the depression symptoms
      were very similar in the two samples. These and other results from the study
      supported a phenomenological continuity hypothesis. Further, although the two
      samples differed quantitatively, the nature of the depressive experience did not
      appear to be one of transient and mild distress for many individuals in the
      analogue sample.

PMID- 9922555
TI  - Diagnostic categories of dental anxiety: a population-based study.
AB  - This study aimed to use a population-based sample to assess the psychological
      validity of the Seattle system for diagnosing dentally anxious individuals. This
      system consists of four diagnostic types in which such individuals are
      categorized according to the main source of their fear regarding dental
      treatment. Subjects were 1420 randomly selected adults aged 18 years and over who
      took part in a two-stage mail survey. The questionnaires contained measures of
      dental anxiety and standardized measures of general anxiety and fearfulness.
      Allocation to the Seattle categories was based on responses to four diagnostic
      items. Overall, 16.4% of the sample were dentally anxious. Their distribution
      across the four Seattle types was as follows: type I (simple conditioned phobia)-
      49.6%; type II (fear of catastrophe)--7.8%; type III (generalized anxiety)--19.4%
      and type IV (distrust of dentists)--9.9%. The remaining 13.3% could not be
      categorized. Judging by their scores on measures of dental anxiety, these
      subjects were borderline cases. Scores on the measures of anxiety and fearfulness
      indicated that the diagnostic system was valid and identified sub-groups of the
      dentally anxious population which were internally consistent. However, all
      subjects indicated extreme fear of dental treatment and were broadly similar in
      terms of their cognitive and behavioral responses to dental care. Of particular
      interest was the distribution of diagnoses according to age. Younger subjects
      were more likely to be categorized as type I, while older subjects were more
      likely to be categorized as type III. Overall, the results indicate that dental
      anxiety is a complex fear with a number of components.

PMID- 9922557
TI  - Dissociation in the laboratory: a comparison of strategies.
AB  - Several methods for inducing dissociation in the laboratory were examined in a
      sample of 78 undergraduate students. Participants scoring high or low on the
      Dissociative Experiences Scale participated in three dissociation challenge
      conditions: (a) dot-staring task, (b) administration of pulsed photic and audio
      stimulation and (c) stimulus deprivation. Participants recorded their
      dissociative experiences both before and after each of the three challenge
      conditions. Across conditions, high DES participants reported significantly more
      dissociative sensations than low DES participants, even after controlling for pre
      challenge dissociation. Moreover, regardless of DES status, pulsed photo and
      audio stimulation produced the greatest level of dissociative symptoms. The
      findings suggest that the induction of dissociative symptoms in a nonclinical
      sample is easily accomplished in the laboratory and that those who report more
      dissociative symptoms in their day-to-day life exhibit more pronounced
      dissociative symptoms when undergoing dissociative challenge in the laboratory.
      Implications for the study and treatment of dissociative symptoms are discussed.

PMID- 9922556
TI  - Water trauma and swimming experiences up to age 9 and fear of water at age 18: a
      longitudinal study.
AB  - A small number of retrospective studies on the etiology of specific fears have
      obtained findings consistent with a biological (non-associative) explanation of
      fear acquisition. Unfortunately, reliance on imperfect memory to recall
      conditioning events which occurred many years earlier limits the conclusions that
      can be drawn from such data. The present investigation attempts to overcome this
      methodological shortcoming by examining the relationship between water trauma
      (i.e. conditioning) and water skills (e.g. swimming) before the age of 9 and the
      presence of water fear and phobia at age 18 in a longitudinal birth cohort. We
      found no evidence of a relationship between water confidence and water trauma up
      to the age of 9 and fear of water at age 18. Similar findings were obtained for
      water phobia at age 18 with the exception that study members who were less able
      to immerse themselves in water with confidence at age 9 were more likely to
      report water phobia at age 18. Associative and non-associative explanations of
      these findings were discussed.

PMID- 9922558
TI  - Visual avoidance in specific phobia.
AB  - Cognitive models of anxiety postulate that fear and anxiety serve as programs for
      avoidance of threat-relevant stimuli. We hypothesized that exposure to phobia
      relevant stimuli would lead to visual avoidance in specific phobics. Spider
      phobic, blood-injection-injury phobic, and nonphobic participants were asked to
      view spider, injection, and neutral photographs through a three-channel
      tachistoscope that measured viewing time for each picture. Despite experimenter
      instructions to study the pictures carefully for a subsequent recognition test,
      phobic subjects showed decreased viewing times for threat-relevant pictures as
      compared to neutral pictures. Results are discussed in terms of cognitive models
      of anxiety disorders and implications for exposure-based therapies.

PMID- 9922559
TI  - Cognitive behavior group therapy for body dysmorphic disorder: a case series.
AB  - The treatment of Body Dysmorphic Disorder (BDD) has received little empirical
      attention despite evidence that BDD is a debilitating mental health problem. This
      open case series provides data on a new cognitive-behavioral treatment for BDD.
      Participants diagnosed with BDD were treated in small groups that met for 12
      weekly 90-minute sessions. Patients improved significantly over the course of
      treatment, with reductions in both BDD and depression symptoms. This finding adds
      to a nascent literature documenting the potential efficacy of short-term
      cognitive-behavior therapy for patients suffering from BDD.

PMID- 9922560
TI  - No interactive effects of naltrexone and benzodiazepines on pain during phobic
      fear.
AB  - Animal research has shown that anxiety may inhibit pain through the release of
      endogenous opioids. On the other hand, anxiety is often believed to exacerbate
      pain in clinical situations, and anxiety reduction has been shown to attenuate
      the affective component of pain. In the present study phobic anxiety was induced
      by confronting forty-eight spider phobic subjects with a spider, after which they
      received two mildly painful electrical stimuli at two different current levels.
      The benzodiazepine alprazolam (1 mg) was administered to investigate the
      influence on pain of a reduction in anxiety, while the role of endogenous opioids
      was studied by administering the opioid antagonist naltrexone (50 mg). Alprazolam
      resulted in lower anxiety and pain ratings during pain stimulation, supporting
      the idea that (presumably pain-related) anxiety may increase the experience of
      pain. Naltrexone did not influence pain and anxiety ratings, nor was there a
      significant interaction between the two pharmacological manipulations. These
      findings confirm previous evidence that phobic fear does not necessarily induce
      an endogenous opioid-mediated analgesia.

PMID- 9922561
TI  - Aggression Questionnaire hostility scale predicts anger in response to
      mistreatment.
AB  - We tested the hypotheses that the hostility and anger scales of the Buss and
      Perry (1992) [Buss, A. H. & Perry, M. (1992). The Aggression Questionnaire.
      Journal of Personality and Social Psychology, 63, 452-459.] Aggression
      Questionnaire would predict anger in college students in response to
      mistreatment. We found low and high hostility groups did not differ in anger at
      baseline or after completing a task without provocation, but the high hostility
      group reported greater anger than the low group after the onset of provocation,
      which required all students to redo completed tasks because some students
      (confederates) were observed cheating. Hostility also influenced anxiety and
      depression, but only anger was greater as a result of the provocation in the high
      than in the low hostility group. The anger scale did not predict anger in
      response to provocation, but anger was higher in the high than the low anger
      group before the provocation. These findings support the construct validity of
      the Aggression Questionnaire hostility scale as a measure of suspicion,
      resentment and sensitivity to mistreatment.

PMID- 9922562
TI  - [He drew divine harmonies from his violin (Paganini)].

PMID- 9922563
TI  - [Complex congenital cardiopathies in adults].

PMID- 9922564
TI  - Functional mitral regurgitation.
AB  - Functional MR is an important complication, which adversely affects the prognosis
      of patients with ischemic heart disease or global LV dysfunction. Two-dimensional
      Doppler echocardiography is a noninvasive and useful method for the diagnosis of
      functional MR. However, the pathophysiology of functional MR is not yet
      established, therefore, extensive investigations are necessary to understand its
      basic mechanism and establish effective and practical method for the prevention
      and treatment of functional MR.

PMID- 9922565
TI  - [Controversies on Mahaim's fibers].

PMID- 9922566
TI  - Physical activity and coronary heart disease.

PMID- 9922567
TI  - [Microalbuminuria, arterial hypertension and the cardiovascular risk].

PMID- 9922568
TI  - [The brain in congestive heart failure in the elderly. Cognitive functions in
      heart failure in the elderly (the CHF Italian Study II). The rationale and
      preliminary data].

PMID- 9922569
TI  - [Chlamydia pneumoniae infection and cardiac ischemic syndromes].
AB  - The aim of this study was to assess the presence of Chlamydia pneumoniae
      antibodies in patients with angiographically verified atherosclerotic coronary
      artery disease. A total of 114 consecutive patients were investigated between
      April 1995 and June 1996. Patients were divided into two groups: 72 patients with
      acute myocardial infarction (AMI; 53 men, 19 women, mean age 62.27 +/- 10.1
      years), and 42 patients with chronic ischemic heart disease (CAD; 37 men, 5
      women, mean age 62.75 +/- 9.2 years). A control group of 50 normal subjects
      matched for age (mean 62 +/- 9 years), sex, social status and geographical area
      was used. Identification of Chlamydia pneumoniae was carried out with the
      microimmunofluorescence method, on two serum samples taken from patients on
      admission and after 15 days. The IgM, IgG and IgA anti-Chlamydia pneumoniae
      titers were assessed, values > or = 1:16, > or = 1:32 and > or = 1:8 being
      respectively considered positive. Acute (IgM > or = 16 or four fold rise of IgG
      titer) and chronic (IgG > or = 128 e IgA > or = 32 or only elevated IgA titer)
      infections were analyzed. IgM antibodies were not found in AMI, CAD and control
      groups. IgG positivity (IgG > or = 32) was found in 38% of the control group, in
      58.3% of the AMI group (p < 0.05) and 42.8% of the CAD group (p < 0.01). IgA
      positivity > or = 8) was found in 22% of the control group, in 31.9% of the AMI
      group (NS) and in 33.3% of the CAD group (p < or = 0.05). Acute infection was
      observed in 5.5% of AMI patients and in 12% of CAD patients (NS), whereas no
      subject of the control group showed these values. Chronic infection was observed
      in 9.7% of AMI patients and in 16.6% of CAD patients (NS) whereas nobody of the
      control group showed these values. In conclusion, our results suggest that
      Chlamydia pneumoniae infection is present only in the AMI and CAD groups. It is
      possible to suppose that this infection may be linked to atherosclerosis through
      an endothelial damage or a systemic endogenous procoagulant and inflammatory
      activity.

PMID- 9922570
TI  - [The prognostic value of type-1 myosin heavy chain in the skeletal muscle of
      patients with chronic heart failure of a mild-moderate degree].
AB  - Patients with chronic heart failure (CHF) develop skeletal muscle disease
      (myopathy) that is in part responsible for the decrease of their exercise
      tolerance. While maximal oxygen consumption (VO2), metabolic equivalent (MET) and
      NYHA functional class are good prognostic indices, it is not known whether
      markers of skeletal muscle myopathy could carry the same meaning. We tested the
      hypothesis that myosin heavy chain 1 (MHC1) could have a prognostic value in 18
      patients with different degree of CHF. Patients were enrolled in January 1995 and
      followed up for 3 years. At baseline all subjects performed cardiopulmonary
      exercise test, echocardiography and gastrocnemius needle biopsy for determination
      of MHC1 percentage. Thereafter patients were divided into two groups (A and B)
      according to MHC1 percentage (< or = 70 and > 70). The number of cardiovascular
      events, the time to the first admission to the hospital and the time to death
      were considered as end points in our study. Eighty-three percent of the events
      and all deaths happened in Group A. The time of the first admission and the
      survival curves were worse in Group A (p = 0.008 and p = 0.02 respectively).
      Similar results were obtained when patients were divided according to VO2 (< or =
      18 and > 18 ml/kg/min), MET (< or = 5 and > 5) and NYHA functional class (III/IV
      and I/II). We also observed a correlation between MHC1, VO2 (r = 0.3, p = 0.01),
      MET (r = 0.5, p = 0.0006) and NYHA functional class (r = 0.1, p = 0.07). In
      conclusion, the CHF myopathy, estimated by MHC1 percentage, gives prognostic
      information similar to VO2, MET and NYHA functional class.

PMID- 9922571
TI  - [Aortic valve replacement in patients over 70: a Doppler echocardiographic
      study].
AB  - Aortic valve disease is known to be the most frequent valvular disease in the
      elderly and aortic valve replacement is often the best therapeutic strategy.
      Hemodynamic performance of prostheses is critical in this subset of patients to
      ensure an optimal quality of life. Moreover, old patients with small aortic ostia
      are getting more and more common in clinical practice, making often necessary to
      implant small prostheses. If a significant pressure drop is not achieved,
      hypertrophy persists and left ventricular function may not improve. Such
      conditions have not yet been extensively studied in the elderly. The aim of this
      study was firstly to assess echocardiographically the performance of aortic
      prosthetic heart valves in old patients (> or = 70 years) and compare the results
      obtained in patients with prostheses of different type and size, and secondly to
      evaluate the postoperative changes in left ventricular hypertrophy and function
      in a subset of patients with isolated or prevalent aortic stenosis. One hundred
      fifty-one patients were initially considered; global mortality was 9.3% at 20 +/-
      12 months from intervention. In the 75 patients with a postoperative
      echocardiogram, transprosthetic gradient was 27 +/- 12 (max) and 15.1 +/- 6.6
      (mean) mmHg. Mean functional prosthetic area (FPA) was 1.5 +/- 0.5 cm2. No
      statistically significant differences could be demonstrated between mechanical
      and biological prostheses. Three groups were identified, according to prosthetic
      size (Group 1: diameter < 23 mm, Group 2: diameter 23 mm, Group 3: diameter > 23
      mm). Among groups, max and mean gradients as well as FPA were found to be
      significantly different. Respectively max gradient was 33.2 +/- 13, 26 +/- 11,
      20.2 +/- 7.2 mmHg (p < 0.05), mean gradient was 17.2 +/- 6.1, 15.4 +/- 7.6, 11.7
      +/- 4.3 mmHg (p < 0.01) and FPA was 1.2 +/- 0.3, 1.5 +/- 0.3, 1.8 +/- 0.7 cm2 (p
      < 0.05 between Group 1 and Group 3). In a subgroup of 31 patients with isolated
      or prevalent aortic stenosis, a significant interventricular septal thickness
      reduction was found postoperatively (14.3 +/- 2.3 vs 12.6 +/- 8.0 mm, p < 0.001).
      Posterior wall thickness decreased similarly, but to a lesser extent; left
      ventricular diameters and myocardial mass also significantly decreased (left
      ventricular mass: 186 +/- 45 vs 146 +/- 38 g/m2, p < 0.001). When prosthetic size
      was considered, septal thickness reduction was more evident in Group 1 and Group
      2 (p < 0.05 and p < 0.01). On the contrary, a significant improvement in left
      ventricular diameters was observed only in Group 3 (p < 0.05). Left ventricular
      mass decreased significantly in Group 2 and Group 3 (p < 0.01 and p < 0.05). Such
      improvements could be demonstrated only in those patients (79%) who showed at
      least a 50% reduction in the transvalvular gradient. In this subset, left
      ventricular function also significantly improved (fractional shortening: 29 +/-
      0.7 vs 33 +/- 0.7%, p < 0.02). In conclusion, aortic valve replacement in the
      elderly is a safe and effective therapeutic strategy. In patients with small
      aortic prostheses, the transvalvular gradient was found to be slightly but
      significantly higher as compared to that of larger prostheses. However, left
      ventricular function was good and similar in all subgroups. No significant
      differences were found between mechanical and biological prostheses. In old
      patients with isolated or prevalent aortic stenosis a significant reduction in
      left ventricular hypertrophy and mass is observed within 2 years from
      intervention. An increase in myocardial contractility can also be expected, if at
      least a 50% reduction in transvalvular gradient is obtained.

PMID- 9922572
TI  - [Idiopathic atrial fibrillation of recent onset and atrial stunning: the
      echocardiographic evidence after pharmacological cardioversion].
AB  - Successful cardioversion of atrial fibrillation may result in prolonged recovery
      of normal atrial mechanical function. This prolonged recovery of atrial
      contraction (so-called atrial stunning) might depend on: the amount of energy
      delivered during direct current cardioversion; the time course between the onset
      of atrial fibrillation and the conversion to sinus rhythm; the size of the left
      atrium; the underlying cardiac disease. The aim of this study was to evaluate, in
      subjects with normal atrial size and without heart disease, the phenomenon of
      atrial stunning soon after pharmacological cardioversion of an episode of atrial
      fibrillation of recent onset. Twenty-five patients with an acute episode of
      atrial fibrillation, without evidence of heart disease and M-mode left atrial
      dimension (< or = 40 mm received i.v. propafenone or flecainide 2 mg/kg/10 min in
      order to restore sinus rhythm. Atrial fibrillation lasted < 48 hours in all
      patients. Doppler echocardiography was used to assess atrial function, by
      recording the peak velocity of atrial contraction (A wave). An echocardiographic
      study was performed within 12 hours of successful cardioversion and was repeated
      on day 3, 12 and 30. The size of the left atrium (37 +/- 3.9; 37.57 +/- 2.9; 37.4
      +/- 4; 37.82 +/- 3.7 mm) and peak E velocity (57.97 +/- 18.3; 59.4 +/- 18.3; 59.0
      +/- 16; 59.07 +/- 16.7 cm/s) did not show any significant differences over the
      time, as demonstrated by the serial echocardiographic evaluations. In contrast,
      both peak A velocity (cm/s) and E/A ratio evaluated within 12 hours of
      cardioversion (60.29 +/- 12.3 and 1.0 +/- 0.37) and on day 3 (73.71 +/- 10.7 and
      0.82 +/- 0.27) were statistically different (p < 0.000001 and p < 0.00001). No
      further statistically significant increase was found in subsequent examinations
      (respectively 76.31 +/- 12 and 0.78 +/- 0.24 on day 12, and 76.91 +/- 14.8 and
      0.78 +/- 0.21 on day 30). In conclusion, this study suggests that patients with
      alone atrial fibrillation of recent onset have a delayed recovery of normal
      atrial systolic function even after pharmacological cardioversion.

PMID- 9922573
TI  - [Endothelin-1 variation in the coronary circulation during angioplasty with a
      stent implant].
AB  - Endothelin-1 (ET-1) is an endothelium-derived mediator with vasoconstrictive and
      mitogenic activity which stimulates vascular smooth muscle cell proliferation.
      The aim of this study was to evaluate ET-1 production during percutaneous
      transluminal coronary angioplasty (PTCA) and elective stent implantation. We
      hypothesized that the additional vessel wall trauma induced by stent deployment
      might be associated with a greater production of ET-1. To this end, ET-1 levels
      were measured in 18 patients undergoing PTCA and stenting (12 with left anterior
      descending coronary artery stenosis and 6 with circumflex artery lesion). The
      sampling sites were the coronary ostium and coronary sinus in basal conditions
      (before the procedure), during first balloon inflation, and 5, 20, 60 min after
      the end of first balloon inflation. At baseline, ET-1 levels were higher in the
      coronary sinus than in coronary ostium (1.58 +/- 0.22 vs 1.29 +/- 0.20 pg/ml, p <
      0.001). During first balloon inflation, ET-1 coronary sinus levels significantly
      diminished with respect to the basal levels (1.08 +/- 0.32 vs 1.58 +/- 0.22
      pg/ml, p < 0.001). Further significant variations of ET-1 levels were not
      detected neither following the first balloon inflation nor after stent
      deployment. In conclusion, the culprit lesion seems to produce most of ET-1
      circulating in the coronary tree. This is demonstrated by higher ET-1 levels in
      the coronary sinus compared to coronary ostium at baseline, and even more by the
      significant ET-1 reduction in the coronary sinus during first balloon inflation.
      Despite our expectations, we did not detect any significant ET-1 increase during
      stent deployment.

PMID- 9922574
TI  - [The Magnum wire for the angioplasty of coronary occlusions and stenoses].
AB  - The "Magnum wire" is a stiff shaft, blunt tip wire constructed for recanalization
      of total coronary occlusions. Smaller series have demonstrated superior qualities
      if compared to conventional wires. The purpose of this study was to analyze its
      efficacy in total and nontotal lesions in a large number of consecutive
      procedures. A database analysis identified the use of the Magnum wire in 569
      procedures from October 1992 to February 1995, which accounted for 26% of all
      angioplasties during the time period at our Institution. There were 347 total
      occlusions and 222 nontotal occlusions. Technical success was achieved in 69% of
      total occlusions and 90% of subtotal occlusions. Procedural success was recorded
      in 58 and 75%, respectively. Stents were implanted in 29 patients with total
      occlusion (8%) and 19 patients with nontotal lesions (9%). Acute occlusion of the
      treated lesion occurred in 4.5% of patients with nontotal lesion and 1.5% of the
      patients with total occlusion. In conclusion, the Magnum wire is an efficient
      tool for angioplasty of total occlusions and severe nonocclusive stenoses. In
      light of the complexity of the attempted lesions, achieved success rates were
      remarkable.

PMID- 9922575
TI  - [Recurrent ventricular fibrillation in acute myocardial infarct treated
      successfully by coronary angioplasty: a clinical case in favor of the hypothesis
      of the arrhythmogenicity of the coronary thrombus?].
AB  - We describe a patient with acute myocardial infarction due to thrombotic
      occlusion of the left anterior descending coronary artery. Following thrombolytic
      therapy, five episodes of ventricular fibrillation recurred despite the absence
      of profibrillatory factors other than myocardial ischemia. Because of
      thrombolysis failure, rescue angioplasty associated with coronary stent
      implantation was performed. After successful mechanical artery recanalization, no
      recurrences of the malignant arrhythmia were observed. This case supports the
      concept, recently demonstrated in animals, that the process of intracoronary
      thrombosis itself may have arrhythmogenic effects above and beyond the impact of
      myocardial ischemia induced by coronary occlusion per se.

PMID- 9922576
TI  - [Cardiac tamponade due to a right atrial myxoma].
AB  - A 60-year-old male patient was urgently admitted to the hospital with chest pain,
      anemia and shock. The echocardiographic examination revealed myocardial tamponade
      and, unexpectedly, a mobile mass in the right atrium, prolapsing in the right
      ventricle which was indicative of myxoma. The patient underwent
      pericardiocentesis which showed the presence of blood. Cardiac surgery was then
      performed to remove the tumor which was found to originate in the right atrial
      appendage. There were some adhesions between the atrial appendage and the
      anterior wall of the right ventricle. The tamponade was due to a trauma of some
      small pericardial arteries in the adhesion area. The presence of tamponade and
      right atrial myxoma, is the peculiar finding of the reported case.

PMID- 9922577
TI  - [The transvenous removal of definitive electrocatheters for stimulation and
      defibrillation: the indications, methods and results].

PMID- 9922578
TI  - [The endothelium and the autonomic nervous system].

PMID- 9922579
TI  - [The aging heart: presbycardia].

PMID- 9922580
TI  - [Cerebral protection in surgery on the aortic arch].

PMID- 9922581
TI  - Diagnosis and prognosis of silent ischemia.
AB  - Patients with coronary disease react differently to ischemia. Some (types I and
      II) experience no symptoms, while most patients with silent ischemia have both
      symptomatic and asymptomatic ischemia. The best evidence suggests that prognosis
      is determined by the amount of ischemia, not its presentation. In addition, in
      these patients, silent ischemia during daily living is not common. Prospective
      prognostic studies have not been performed in patients who do not experience
      angina with ischemia, therefore treatment must be individualized in these
      patients, considering the lack of a "warning system".

PMID- 9922582
TI  - [The postinfarct stratification of arrhythmic risk: the return to favor of an
      obsolete fashion or an effective clinical necessity?].

PMID- 9922583
TI  - Single-drug therapy and reduction of left ventricular mass in hypertension.
AB  - Echocardiography has provided most of what is understood today about the
      relationships between human hypertension, cardiac anatomic and functional
      responses. It has proven its value in determining the effects of antihypertensive
      therapy on cardiac structure and function. A growing body of research supports
      initial concerns that not all drugs effective for blood pressure reduction are
      effective for reduction of left ventricular mass and regression of LVH. It has
      been of interest that agents initially believed to be ineffective for left
      ventricular mass reduction (principally diuretics and beta blockers) on the basis
      of pathophysiological theory and inadequate clinical trials, may in fact be quite
      effective for LVH regression, as well as improved cardiac outcomes. Hence,
      supposed inefficacy of these agents for this purpose should no longer be used as
      a reason to disregard long-standing recommendations of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension
      supporting the use of diuretics and beta blockers for the initial pharmacotherapy
      of hypertension.

PMID- 9922584
TI  - [The role of the GH/IGF-1 axis in cardiovascular physiopathology and therapy: the
      lessons from animal studies].

PMID- 9922585
TI  - [Intra- and extravascular volumes in congestive heart failure and their
      redistribution following extracorporeal ultrafiltration].
AB  - In advanced congestive heart failure with fluid retention, extracorporeal
      ultrafiltration (UF) causes persistent relief of edema or anasarca through
      hemodynamic and humoral changes that interrupt refractoriness to diuretics. The
      intra and extravascular fluid partition in congestive heart failure, as well as
      changes occurring in the two compartments following fluid withdrawal with UF, are
      unknown. In 8 congestive heart failure patients with severe fluid retention
      undergoing UF, we measured total (TBV), intrathoracic (ITBV) and pulmonary blood
      volumes (PBV), and extravascular lung water (EVLW). The intra and extravascular
      volumes were evaluated by a fiberoptic thermal dye dilution monitoring system,
      before, at the end of UF (3697 +/- 699 ml) and 24 hours later. Baseline data were
      compared with those of 10 subjects without heart failure undergoing coronary
      bypass surgery. In congestive heart failure patients, as compared with controls,
      TBV was normal, the intrathoracic blood content (ITBV, PBV and PBV/TBV ratio) was
      increased and EVLW was normal. UF did not induce significant changes in TBV and
      in EVLW, and reduced ITBV, PBV and PBV/TBV ratio, suggesting that a shift of
      fluid from the intra to the extrathoracic intravascular compartment occurred.
      Because both TBV and EVLW were not affected by the procedure, the largest
      proportion of fluid removed by UF derived from the systemic extravascular space.
      Both pulmonary wedge and right atrial pressures significantly decreased after UF,
      and cardiac output increased. In conclusion, congestive heart failure is
      associated with normal TBV and EVLW content and with intravascular intrathoracic
      hypervolemia and extrathoracic hypovolemia. UF induces hemodynamic improvement
      through a selective fluid removal from the extravascular systemic space without
      changes in both TBV and EVLW.

PMID- 9922586
TI  - [Dynamic obstruction to left ventricular outflow during dobutamine stress
      echocardiography: the probable mechanisms and clinical implications].
AB  - We observed the development of left ventricular outflow tract dynamic obstruction
      in some patients during dobutamine stress echocardiography. The purpose of this
      study was to identify the possible mechanisms and to consider the clinical
      implications. From 11/04/94 to 01/09/97 we studied 547 patients; 42 patients
      developed dynamic obstruction, defined as a late peak Doppler velocity profile
      that exceeded baseline outflow velocity by at least 1 m/s. The encountered
      mechanisms were: increased myocardial contractility; systolic anterior motion of
      the mitral valve; decreased venous return to the left ventricle, and peculiar
      characteristics of the left ventricular geometry. The results of this study show
      that the dynamic obstruction is mainly due to the first mechanism and secondarily
      to some characteristics of the left ventricular geometry. The hypotension
      observed in a few cases is not related to the dynamic obstruction but to beta 2
      receptor hypersensibility to dobutamine. The symptoms, like dyspnea and chest
      pain, experienced by these patients are related to the dynamic obstruction rather
      than to the presence of coronary artery disease. In conclusion, we think that
      patients who develop dynamic obstruction, without wall motion abnormalities,
      during dobutamine stress echocardiography, may behave pathophysiologically as
      patients with obstructive hypertrophic cardiomyopathy, in whom diastolic
      dysfunction and outflow tract obstruction are responsible for symptoms.
      Therefore, these patients require a pharmacological treatment with beta blockers
      and/or non-dihydropyridine calcium channel blockers.

PMID- 9922588
TI  - [Anatomico-functional changes in the right ventricle of the athlete].
AB  - The aim of this study was to compare the morpho-functional modifications of the
      right cardiac sections of the athlete's heart, with those of sedentary healthy
      control subjects. We studied 24 endurance athletes (mean age 28.17 +/- 7.28
      years), 21 power athletes (mean age 25.86 +/- 4.96 years), and 20 sedentary
      healthy control subjects (mean age 33.22 +/- 6.67 years). We examined the right
      cavities by standard echocardiographic projections and the following parameters
      were evaluated: right ventricular longitudinal diameter; under tricuspid valve
      and medium ventricular transversal diameter immediately under the tricuspid plane
      and at medium ventricular level; right atrial transversal and longitudinal
      diameters. All parameters were corrected for body surface area. Our data showed
      that the right ventricle presents morphological adaptations to endurance
      exercise; modification is represented mainly by an increase in the mean
      transversal ventricular diameter with a consequent reduction in the
      transversal/longitudinal diameter ratio accompanied by modification of the
      ventricular geometry. In addition the data showed an increase in longitudinal and
      transversal diameters of the right atrium. On the contrary, the power athletes
      did not show statistical modification of the right ventricle and atrium. The
      different modifications of the right heart side diameter are probably due to the
      different hemodynamic loading, which is involved in the endurance and power
      training respectively.

PMID- 9922587
TI  - [The absence of a procoagulant effect after TNK-t-PA: a comparison with
      streptokinase and rt-PA].
AB  - A limitation of current fibrinolytic drugs is the procoagulant activity induced
      by their administration. TNK is a mutant of tissue plasminogen activator (t-PA)
      with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and
      slow plasma clearance, which is administered in a single intravenous bolus. In
      this study we investigated the procoagulant effect of TNK-t-PA compared to
      streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute
      myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU
      streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40
      mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with
      contraindications to thrombolysis (control group). All patients received a
      similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn
      before the start of treatment (time 0) and after 2 hours. Thrombin formation was
      assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The
      four patient groups did not differ significantly in age, sex, time to treatment,
      infarct location, and TAT values at time 0 (mean value +/- standard error of the
      mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l
      in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in
      rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK
      treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK
      and controls). In conclusion, our data suggest that, in patients with acute
      myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions,
      is devoid of procoagulant effects, evaluated 2 hours after its administration.

PMID- 9922589
TI  - [Initial experience with the use of abciximab in the salvage treatment of acute
      coronary thrombosis in the Hemodynamics Laboratory].
AB  - The optimal treatment of acute thrombotic complications in the Catheterization
      Laboratory has not been defined yet, due to the limited efficacy shown by various
      pharmacological regimens, even when associated to coronary angioplasty (PTCA).
      The aim of our study was therefore to evaluate the effects of abciximab (ReoPro),
      a new potent inhibitor of the platelet glycoprotein IIb/IIIa, when administered
      as a "rescue" treatment for acute thrombotic coronary occlusion during diagnostic
      or interventional procedures. Sixteen patients (12 males, 4 females, mean age
      59.3 +/- 9.2 years, range 43-77 years), with unstable angina and consecutively
      treated with abciximab due to clinical instability attributable to coronary
      thrombosis angiographically proven during PTCA (9 cases) or diagnostic
      angiography (7 cases), were identified. The individual angiographic films and
      medical records were then reviewed in order to evaluate the effects of treatment
      on coronary flow, thrombus size and occurrence of in-hospital adverse events:
      death, non-fatal acute myocardial infarction (AMI), need for urgent myocardial
      revascularization and hemorrhage. The administration of abciximab, in association
      with PTCA (associated in turn with stent implantation in 8 cases), induced a
      significant increase of coronary TIMI flow grade (0.3 +/- 0.6 vs 2.4 +/- 0.9; p <
      0.05) and a significant decrease of thrombus "score" (size) 2.4 +/- 0.9 vs 1.3 +/
      0.6; p < 0.01). No deaths nor need for urgent myocardial revascularization were
      observed; in 31% of cases (5 patients) evolution towards AMI occurred, while
      however 94% of cases (15 patients) had a coronary occlusion before treatment. No
      major hemorrhagic complications were observed, while in 12% of cases (2 patients)
      a groin hematoma associated with moderate hemoglobin drop, developed. In
      conclusion, the administration of abciximab, associated with the common "rescue"
      interventional procedures, in patients with acute thrombotic coronary occlusion
      in the Catheterization Laboratory, appears to be effective in restoring adequate
      coronary flow and reducing the thrombus size (limiting therefore the evolution
      towards AMI), and safe, not having been associated with significant hemorrhagic
      complications.

PMID- 9922590
TI  - [The heterogeneity of myocardial sympathetic innervation in normal subjects: an
      assessment by iodine-123 metaiodobenzylguanidine scintigraphy].
AB  - 123I-radiolabeled metaiodobenzylguanidine (123I-MIBG) cardiac imaging has been
      used to evaluate the distribution of sympathetic nervous system (SNS) in the
      heart. Different heart diseases have shown impaired cardiac SNS distribution as
      reflected by MIBG activity. The aim of this study was to assess the cardiac
      distribution of SNS in normal subjects, using MIBG imaging. Ten normal subjects
      (1 male and 9 females, mean age 46 +/- 9 years) with no cardiac abnormalities
      underwent myocardial 123I-MIBG scintigraphy, Tc-99m methoxyisobutylisonitrile
      (MIBI) cardiac perfusion imaging and equilibrium radionuclide angiography (RNA).
      Regional myocardial MIBG and MIBI activities were quantitatively evaluated using
      a region of interest analysis. For this purpose, the left ventricle was divided
      into 6 myocardial regions as anterior, apical, inferior, septum, lateral and
      posterolateral. In particular, myocardial MIBG and MIBI activities were measured
      as myocardium to mediastinum ratio. Regional left ventricular function was
      assessed by RNA. Myocardial MIBG uptake was homogeneous in anterior (2.2 +/-
      0.5), inferior (2.5 +/- 0.7), septal (2.4 +/- 0.4), lateral (2.3 +/- 0.4), and
      posterolateral (2.3 +/- 0.4) regions. Conversely, MIBG uptake was significantly
      lower in the apical region (1.9 +/- 0.3) compared to all other left ventricular
      segments (p < 0.05). Regional myocardial perfusion, as measured by MIBI uptake,
      was homogeneous in all regions. No regional left ventricular wall motion
      abnormalities were observed by RNA. In conclusion, our data suggest that a
      decreased MIBG uptake may be observed in the left ventricular apical region of
      normal subjects reflecting reduced sympathetic innervation of the apex. This
      finding is not related to myocardial perfusion or wall motion abnormalities. The
      knowledge of cardiac sympathetic innervation in normal subjects may be helpful to
      assess SNS abnormalities in heart disease.

PMID- 9922591
TI  - [Mini-invasive cardiac surgery: a fashion or an epochal turning-point?].

PMID- 9922592
TI  - The ileal pouch-anal anastomosis: success and failure.

PMID- 9922593
TI  - [Xenograft: great hopes about an old idea].

PMID- 9922595
TI  - [Malignant tumors of the ampulla of Vater. Results of radical excision. A study
      of 39 cases].
AB  - STUDY AIM: From 1971 to 1995, 39 patients underwent curative resection of a
      malignant tumor of the ampulla of Vater. The aim of this retrospective study was
      to report long-term results and to determine factors influencing survival in
      these patients. PATIENTS AND METHODS: Data was collected from patient record
      analysis, correspondence with patients, their family or general physician. Kaplan
      Meier method was used to compare survival data by the log-rank test. Multivariate
      analysis evaluated the impact of each variable on survival. Values with a P value
      of 0.05 or less were considered statistically significant. RESULTS: Resection
      consisted of pylorus preserving pancreaticoduodenectomy (n = 21) or pancreatico
      duodenectomy associated with an antrectomy (n = 18). Overall mortality rate after
      resection was 10% (n = 4). General and specific morbidity rates were 71% and
      2.5%. During the course of the follow-up (completeness: 100%) mean survival was
      80 months (median: 37 months, range: 6-227 months). Five-year survival rate was
      35%. Factors favorably influencing long-term outcome were exposed protruding and
      well differentiated tumors (P = 0.03, P = 0.01, respectively) and negative lymph
      node status (P = 0.0001). Prognosis was poorer if tumor was extended into the
      pancreas (P = 0.04). Among proposed histoprognostic classifications
      (classifications of Martin, Talbot, Shirai, Yamaguchi), an excellent correlation
      was obtained only with TNM classification (P = 0.0001). CONCLUSION: Results of
      the present study suggest that prolonged survival can be obtained following
      radical resection of a malignant tumor of the ampulla of Vater, especially for
      exposed protruding and well differentiated tumors, without extension into the
      pancreas or lymph node metastasis. TNM classification provides an excellent
      predictive value and should be used more systematically.

PMID- 9922594
TI  - [Results of the surgical treatment of severe caustic pharyngo-esophageal
      stenosis. The value of complete reconstruction of the pharynx by transposition of
      the ileum and colon].
AB  - STUDY AIM: The aim of this study was to report the results of pharyngoesophageal
      reconstruction in extensive corrosive strictures and to describe an original
      conception concerning extensive chemical burns of the pharynx with involvement of
      the epiglottis, oro-hypopharyngeal junction and cricopharyngeal pinchcock.
      PATIENTS AND METHODS: A personal series of 253 esophageal reconstructions using
      the colon and ileum is reported. In 124 patients, the cervical anastomosis of the
      graft was performed at the level of the pharynx, and these cases with extensive
      pharyngeal lesions were the basis of this study. The anastomosis was performed
      with the hypopharynx in 27 patients, with the oropharynx in nine and a total
      reconstruction of the pharynx or "pharyngoplasty" was carried out in 69 patients.
      The pharyngoplasty was classified according to the approach, in anterior,
      posterior, lateral, superior (transmandibular) and inferior. In high strictures
      with epiglottic injury, epiglottectomy was necessary in order to prevent
      recurrence. A visceral pharyngoplasty was performed in 61 patients, using the
      colon in 42 and the ileum in 19, a skin reconstruction in six patients and a
      myocutaneous flap in two. RESULTS: The global postoperative mortality rate was
      4.7%. Stenosis of the cervical anastomosis occurred in 4.9% of the whole series.
      With a follow-up from 6 months to 10 years, 70% of the patients resumed a normal
      oral diet, 21% had mild symptoms and 7% had poor results (patients with
      tracheostomy and gastrostomy). CONCLUSION: Extensive chemical burns of the
      pharynx are very severe and their treatment very difficult. For the author, total
      visceral pharyngeal reconstruction is considered to be the procedure of choice,
      using ileopharyngoplasty with realization of an ileal pouch. Good results were
      obtained in 70% of the patients with extensive corrosive strictures.

PMID- 9922596
TI  - [Implantation of autologous chondrocytes for cartilagenous lesions in young
      patients. A study of 24 cases].
AB  - STUDY AIM: The aim of this study was to describe the treatment of symptomatic
      knee cartilage defects on young active patients by autologous chondrocyte
      implantation and to report preliminary results in 24 patients. PATIENTS AND
      METHODS: Since April 1996, 24 selected patients underwent 25 implantations in
      five military hospitals. There were 19 men and five women (all of them practicing
      sports); mean age was 27. Lesions were localized on left (n = 13) and right (n =
      12) aligned and stabilized knees. There were 12 isolated cartilage defects (eight
      OCD and four posttraumatic) and 13 associated with ligament lesions (n = 8) or
      multiple and severe lesions (n = 3 indication of salvage). Mean surface of
      cartilage defects was 6 cm2. Mean preoperative evolution was 11 months and stage
      was grade IV (Outerbridge) for all. The first step was arthroscopy for
      classification and biopsy. The second one was implantation after a 3-week delay
      (for the ex vivo culture) through arthrotomy, under a periosteal flap taken from
      tibia and sutured on the edges of the prepared defect. Weight bearing was allowed
      after the 6th week; MRI was performed at 6, 12, 18, 24 months. The follow up was
      evaluated with three scales: Lysholm 2, Tegner Activity, Cincinnati Knee Rating
      System. RESULTS: Postoperative complications included: algodystrophy (n = 2) and
      phlebitis (n = 1). Four patients were revised at 6 months, seven between 6 and 12
      months, 11 after. The longest follow-up was 26 months. Results were poor in one
      patient (salvage). For the others, pain and swelling decreased after 6 months and
      disappeared after 12 months. CONCLUSION: Autologous chondrocyte implantation used
      in this senes and in a large international ongoing series seems to be the only
      procedure allowing a true long-term regeneration of cartilage defects. Some
      questions remain, on the biological level in relation with the use of some growth
      factors and the risk of chromosomic abnormalities, and on the economical level
      because of the high cost of this technique.

PMID- 9922597
TI  - [Tricalcium phosphate, an antibiotic carrier: a study focused on experimental
      osteomyelitis in rabbits].
AB  - PURPOSE OF THE STUDY: Macroporous beta tricalcium phosphate ceramic beads were
      elaborated to be a resorbable bone substitute and a drug delivery system carrying
      gentamicin or vancomycin. The aim of this study was to evaluate this implant into
      a rabbit experimental osteomyelitis. MATERIAL AND METHOD: Experimentation
      included 24 rabbits and was performed in three stages, according to Norden's
      description. Induction of osteomyelitis was obtained by injection of a sclerosing
      agent and of Staphylococcus aureus through the lateral side of the metaphysis of
      the proximal tibia. Three weeks after inoculation, animals were randomly
      dispatched to one of the three treatment groups. After surgical debridment (to
      collect cinetics data), the first group received no further treatment and was
      considered as a control; the second group received a ceramic implant; the third
      group received a gentamicin-loaded ceramic implant. Euthanasia occurred between 2
      days and 21 days after the debridment. Bone samples were obtained to quantify the
      bacterial and gentamicin bone concentrations. Gentamicin level was also measured
      inside the ceramic implant. Antibiotic concentration was assessed by a
      immunoenzymatic method. RESULTS: Osteomyelitis was obtained in 21 of the 24
      animals (87.5%). Antibiotic release was early and complete (before the third day)
      but gentamicin still remained in the bone for 10 days. Bacterial concentration
      suggested an antimicrobial activity of the implant, but not a full sterilisation
      of the osteomyelitis. CONCLUSION: Norden's experimental osteomyelitis model with
      rabbit was proposed to assess the therapeutic activity of systemic antibiotics,
      but not to evaluate biomaterials. Therefore we have shifted for experimental
      evaluation of biomaterials to a metaphyseal osteomyelitis in the sheep, the
      patterns of which are close from those of the human disease.

PMID- 9922598
TI  - [Virtual laparoscopic anatomy of the esophagogastric junction].
AB  - The anatomy of the GE junction is represented by computer synthetised pictures.
      This method allows to represent different organs from different angles, emphasis
      being put on the laparoscopic angle of vision. This should improve anatomical
      comprehension. The synthetic pictures have been constructed in a figurative
      representation. Fatty tissues have been omitted whereas the peritoneal layers
      covering organs and defining spaces are enhanced.

PMID- 9922599
TI  - [Functional results of the laparoscopic treatment of gastroesophageal reflux
      (followup greater than 2 years)].
AB  - STUDY AIM: The of this study was to evaluate functional results in 70 patients
      operated on for gastroesophageal reflux disease with a follow-up > 2 years, by
      means of a questionnaire sent to them. PATIENTS AND METHODS: Functional results
      were evaluated in the 60 patients who answered the questionnaire. The
      fundoplication (Nissen = 27, Nissen-Rosseti = 21, Toupet (n = 12) was
      laparoscopically performed with a mean follow-up of 3.4 years (range: 2-6.6
      years). A circular wrap (either Nissen or Nissen-Rossetti) had been
      systematically performed except in patients who had an esophageal motility
      disorder, who had a partial wrap according to Toupet. RESULTS: Three patients
      experienced recurrent symptoms of reflux (failure rate: 5%). Thirteen patients
      had mild dysphagia, requiring modification of the oral intake in two cases. No
      patient required dilatation. Fifty patients complained of postoperative side
      effects: flatulence (n = 40), meteorism (n = 24), abdominal pain (n = 16),
      diarrhea (n = 12), impossibility either to vomit (n = 16) or to belch (n = 20).
      Ten patients were symptom free and had neither symptoms of reflux nor side
      effects. Despite undesirable side effects, 46 patients (78%) were very satisfied
      with the operation, six (10%) were satisfied and five (8%) were disappointed.
      CONCLUSION: Recurrent symptoms of reflux were rarely observed (5%) but
      postoperative side effects were frequent (67%). Side effects when present provide
      less discomfort than reflux itself. Patients must be aware of it prior to
      surgery. These results should be confirmed by further assessments.

PMID- 9922600
TI  - [Videolaparoscopic treatment of paraesophageal hiatal hernia].
AB  - STUDY AIM: The aim of this prospective study was to report the results of
      videolaparoscopic repair in a series of ten patients with paraesophageal hernia.
      PATIENTS AND METHODS: From January 1982 to September 1998, ten patients (three
      men and seven women, mean age: 68 years [range: 42-87]) were operated on for
      paraesophageal hernia. An intrathoracic gastric volvulus was present in four
      patients, a severe anemia in four and two were asymptomatic. All interventions
      were performed laparoscopically and included sac resection, crura closure and
      realization of a posterior gastric valve on 270 degrees. RESULTS: There was one
      irruption of gastric juice in the bronchial tree at the beginning of the
      anesthesia which required assisted ventilation for 3 days. The mean follow-up was
      17.5 months (range: 3-50). There was no postoperative diarrhea and no gas bloat
      syndrome. Eight patients complained of postoperative dysphagia which disappeared
      within 6 weeks, except in one patient with esophageal motility disorder
      postoperatively discovered. None of the patients had postoperative
      gastroesophageal reflux. A chest X-ray performed after 1 year detected no hernia
      recurrence in seven patients. There was no recurrent anemia after 6 months.
      CONCLUSION: The videolaparoscopic repair of paraesophageal hernias is feasible
      without any technical difficulties even in aged patients with precarious physical
      conditions. The results are good with a mean follow-up of 17.5 months.

PMID- 9922601
TI  - [Videolaparoscopic treatment of splenic injuries. A study of 5 cases].
AB  - BACKGROUND: When splenic trauma does not require an emergency splenectomy in
      order to achieve hemostasis, the current policy is either observation under close
      surveillance, with transfusions if necessary, or conservative surgical procedure
      through laparotomy. Videolaparoscopic approach has the advantage of achieving in
      the same procedure, complete evacuation of the hemoperitoneum, full investigation
      of the abdominal cavity and repair of the damaged spleen. PATIENTS AND METHODS:
      Over a 4-year period, five patients aged 27.3 years on average, with severe
      splenic trauma but no major hemodynamic disturbance, were operated on by
      emergency laparoscopy. The diagnosis of splenic lesion had been confirmed
      preoperatively by ultrasonography. The procedure performed by open laparoscopy
      included evacuation of the hemoperitoneum and blood clots and splenic hemostasis
      which was achieved by the use of electrocoagulation and biological glue,
      associated in three cases with omentoplasty. Drains were inserted systematically.
      RESULTS: The average length of operation was 75 min. There were no cases of
      conversion, nor mortality, no morbidity. The average duration of hospitalization
      was 10 days. No blood transfusions were required. A CT-scan was performed
      immediately in the postoperative course and served as the baseline for comparison
      during the follow-up. There were no reinterventions. The longest follow-up was 4
      years and the mean follow-up 2.5 years. Laboratory tests or isotopic imaging did
      not detect any change in splenic function. CONCLUSION: In specific defined
      circumstances, videolaparoscopic repair of splenic trauma is justified provided
      that careful attention is paid to the patient's condition.

PMID- 9922602
TI  - [Hyperthyroidism and cancer of the thyroid].
AB  - STUDY AIM: The idea that thyrotoxicosis is insurance against thyroid cancer has
      prevailed for a long time. However this association has been reported frequently
      in the recent literature. The aim of this study is to report our experience
      concerning this association and to discuss its incidence and its consequences in
      the light of the present data. PATIENTS AND METHOD: Among the 734 patients who
      underwent a thyroidectomy between January 1983 and January 1998, there were 125
      patients with hyperthyroidism, ten with associated cancer (8%). All patients were
      female (mean age: 43.8 years) with Graves' disease (n = 2), a toxic adenoma (n =
      5), or a multi nodular toxic goiter (n = 3). The cancer was recognized
      intraoperatively in eight patients. A total thyroidectomy was performed in five
      cases and a total lobectomy associated with a subtotal contralateral lobectomy in
      five cases, completed by a treatment with l131 in nine cases. RESULTS: Concurrent
      carcinoma was present in 10% of the patients with toxic nodular goiter and in
      4.4% in those with Graves' disease. Papillary carcinoma presented in all cases.
      The size of the cancer was between 0.2 and 1.5 cm. Nodal involvement was present
      in one patient. With a follow-up of 1 to 15 years, there was no local recurrence
      and no metastasis. CONCLUSION: The diagnosis of hyperthyroidism does not preclude
      concurrent thyroid carcinoma. The prognostic and therapeutic consequences of this
      association are still debated.

PMID- 9922603
TI  - [Deteriorating choledochal cyst. A case].
AB  - Choledochal cysts have an increased risk of biliary tract malignancy, induced by
      reflux of pancreatic juice and anomalous pancreatobiliary ductal junction. We
      report one case of congenital choledochal cyst in a 68-year-old female whose
      malignancy was revealed by history of pain and jaundice. Pancreatico-duodenectomy
      was performed and the patient was alive 6 months later.

PMID- 9922604
TI  - [Parietal tumor seeding after thoracoscopic surgery: apropos of a case].
AB  - The authors report one case of port site recurrence 5 months after thoracoscopic
      resection of a pulmonary metastasis in a 68-year-old woman.

PMID- 9922605
TI  - [The origin of modern mechanical sutures in surgery: short and long stories, in
      hommage to Mark Ravitch].

PMID- 9922606
TI  - Dentine permeability and tracer tests.
AB  - OBJECTIVES: This paper reviews the evidence for dentine's permeability in order
      to clarify and emphasize its confounding effect on leakage test measurements, and
      hence the need to use special test designs to avoid its effects. METHODS: The
      literature on the subject between 1887 and 1997, including 249 articles.
      CONCLUSIONS: The prerequisite condition for any tracer penetration test is that
      unflawed specimens are themselves impermeable to tracer. Entry of tracer then can
      be used to indicate correctly the location or severity of flaws. The relative
      impermeability of intact dental enamel permits such testing of the enamel
      restoration interface seal, but the same is not true when using dentine, which is
      usually frankly porous to most tracers through its tubules. False positive
      results are very likely. Recent intense interest in dentine bonding agents has
      increased the need and frequency of these tests with dentine, but this serious
      confounding factor has so far generally remained unstated, and has only been
      controlled adequately in one study. If tracer penetration test results are to be
      meaningful, then adequate control is required.

PMID- 9922607
TI  - Clinical evaluation of a posterior composite 10-year report.
AB  - OBJECTIVE: The 10-year findings of one of the studies which comprised the
      multicentre clinical evaluation of a light-cured posterior composite restorative
      are reported, with special emphasis on the reasons and timing of failure of
      restorations included in the study. Effects of the use of rubber dam or cotton
      rolls and aspiration for isolation at the time of placement are considered.
      METHOD: One hundred Class I and II restorations of the resin composite
      investigated were placed by a single operator in a group of selected,
      predominantly young-adult patients under highly controlled conditions, with the
      use of rubber dam or cotton rolls and aspiration for isolation being determined
      according to a scheme of randomisation. The restorations were reviewed clinically
      after 1 week and within 1 month of placement (baseline) and, thereafter, at 6
      months, 1, 2, 3, 4, 5, 6 and 10 years using modified USPHS codes and criteria.
      Epoxy models and photographs were obtained for retrospective analysis. RESULTS:
      After 10 years, 37 restorations were reviewed and 32 restorations were known to
      have failed. Regarding the reasons for failure, loss of occlusal anatomic form
      during the first 5 years and loss of approximal contacts near the end of the
      study accounted for most of the failures. Only two failures were attributed to
      recurrent caries. Few of the restorations found to be clinically satisfactory at
      10 years had retained ideal functional characteristics. Location, Class and size
      of restoration and the method of isolation were not found to significantly
      influence 10-year performance and survival. CONCLUSION: The actual 10-year
      failure rate, estimated to have been between 40 and 50% is considered to have
      been high, notably given the limited incidence of recurrent caries and bulk
      fracture. However, the findings indicate that certain restorations of the
      material investigated, despite the use of outdated operative techniques, may be
      found to perform satisfactorily over periods in excess of 10 years.

PMID- 9922608
TI  - Oral health status of southern Chinese following head and neck irradiation
      therapy for nasopharyngeal carcinoma.
AB  - OBJECTIVE: To investigate the oral health status of patients with nasopharyngeal
      carcinoma (NPC) after completion of radiotherapy. METHODS: Thirty-three NPC
      patients (mean age 53 +/- 10 years) who had completed head and neck radiotherapy
      (3.6 +/- 3.1 years post-operation) were examined. Dental caries, periodontal
      status and oral mucosal lesions were recorded. Stimulated whole saliva (SWS) flow
      rate, pH, buffer capacity and carriage rate of carcinogenic micro-organisms were
      assessed. Jaw opening was measured. RESULTS: Xerostomia was present in all
      patients, while 42% had candidiasis and 21% had limited jaw opening. The mean
      number of teeth present was 22, mean DMFT was 8.0, mean number of untreated root
      caries lesions was 1.4. Both saliva pH and buffering capacity were low while
      Streptococcus mutans and Lactobacillus spp. carriage were high. 52% of the
      patients had no dental care following radiotherapy. Although few patients
      expressed direct dissatisfaction, perceived level of information and of post
      operative dental care was insufficient. CONCLUSIONS: Post-irradiated NPC patients
      constitute a high-risk group for dental root caries and oral candidiasis. The
      carriage rate of Streptococcus mutans and Lactobacillus spp. in this NPC patient
      group was the highest among findings of other similar studies. This may be
      related to the inadequacy of dental care after radiotherapy. Head and neck
      radiotherapy was not associated with periodontal disease.

PMID- 9922609
TI  - Cuspal deflection during polymerisation of composite lutes of ceramic inlays.
AB  - OBJECTIVE: The purpose of this study was to measure the cuspal deflection that
      occurs in teeth as a result of the dimensional changes of resin-based lutes
      during polymerisation. METHODS: Standardised MOD cavities were cut in 15 intact
      human premolar teeth using a custom paralleling device. A ceramic inlay was
      machined by the CEREC 2 system for each tooth ensuring an interface width of 50
      microns (SD = 17.5) at the cavity margin. The 15 teeth were divided into three
      groups of five according to the cementation system employed: a microfilled hybrid
      posterior composite; a compomer restorative; a dual-cure luting composite. The
      inter-cuspal tooth dimension was recorded continuously with a laser micrometer
      assembly during a 2 min photoactivation period and a further 30 min post
      activation period. RESULTS: A clear overall reduction in tooth dimension was
      detectable for the first 10 min of polymerisation. The mean changes ranged from 
      0.02% to -0.06% depending on the nature of the luting material. In addition, all
      samples exhibited a slight expansion of 0.03% during the time of light
      activation. CONCLUSIONS: The dimensional changes that teeth experience during the
      polymerisation of resin-based lutes are clearly detectable. It can be postulated
      that an increase in the dimensions of the teeth during photoactivation occurs as
      a result of expansion of the lute due to the thermal energy delivered.

PMID- 9922610
TI  - The influence of luting cements on the fermentation of sucrose by oral
      microorganisms.
AB  - OBJECTIVES: Three luting cements based on zinc oxide phosphate, glass ionomer or
      composite resin were compared with respect to their influence on the anaerobic
      fermentation of sucrose by human oral bacteria. METHODS: Fifteen standardized
      samples of each of the three luting cements were prepared according to the
      manufacturer's instructions and stored for 72 h at 37 degrees C in distilled
      water, which was also used as elution medium. After removing the samples
      solutions were incubated with human fasting saliva, sucrose and a bicarbonate
      buffer in a Warburg apparatus. Intermediary organic acids resulting from
      anaerobic fermentation of sucrose were quantified indirectly by manometric
      measurement of CO2, released from the buffer. RESULTS: The materials did not
      indicate either an accelerating or an inhibiting effect on the formation of
      organic acids from sucrose. CONCLUSION: In the case of bacterial microleakage
      along the interface between cavity and luting cement, an inhibition of acid
      induced dentin or enamel demineralisation--using the materials investigated-
      cannot be expected.

PMID- 9922611
TI  - Effect of endodontic irrigation solutions on microhardness of root canal dentine.
AB  - OBJECTIVES: This study was undertaken to evaluate the effect of several
      endodontic irrigation solutions on the microhardness of root canal dentine.
      METHODS: Eighteen freshly extracted maxillary incisors were used in this
      experiment. The crowns of teeth were sectioned at the cemento-enamel junction.
      The root canals were instrumented to an apical size #50 file, and irrigated with
      saline solution. The prepared roots were divided equally into two groups each of
      nine roots. Each root was sectioned transversely into cervical, middle and apical
      segments. The three sections of each root were separately mounted in a metal
      chuck with acrylic resin. The coronal dentine surfaces of the root segments were
      polished. The microhardness of the dentine was measured for the purposes of
      control data at 500 microns and 1 mm from the pulpo-dentinal interface. The canal
      portions in the root segments included in the first group were irrigated with 3%
      H2O2 and 5% NaOCl solutions used alternatively, while 17% EDTA solution was the
      irrigation used in the second group. One millilitre of each solution/segment was
      applied for 60 s exposure time. After irrigation, dentine microhardness was re
      assessed and compared with the control values obtained before the irrigation
      treatment. Data were statistically analysed using ANOVA and Scheffe's test.
      RESULTS: The results showed that, irrigation with either H2O2/NaOCl or EDTA
      decreased the microhardness value of root dentine. Irrigation with EDTA gave more
      reduction of dentine hardness compared to H2O2/NaOCl irrigation. The reduction of
      KHN of dentine following the irrigation treatment was statistically significant
      (p < 0.05) at both levels of hardness measurement. CONCLUSIONS: Both H2O2/NaOCl
      and EDTA irrigating solutions significantly reduced the microhardness of root
      canal dentine.

PMID- 9922612
TI  - Cusp fracture resistance in composite-amalgam combined restorations.
AB  - OBJECTIVE: To evaluate the in vitro resistance to fracture and microleakage in
      composite-amalgam combined restorations. METHODS: Seventeen Class I cavities with
      unsupported enamel walls prepared in extracted permanent molar teeth were treated
      with a bonding agent (Scotchbond MP, 3M Dental), the buccal cusps were reinforced
      with a composite resin (Z-100, 3M Dental) and the cavities were then restored
      with amalgam (Permite, Oral B). All teeth were load tested using a special
      fatigue-stress apparatus, immersed in a dye solution and then sectioned for
      examination by stereomicroscopy and scanning electron microscopy (SEM). RESULTS:
      Fractures in enamel supported by composite were present in 11 cases while 12
      specimens included fractures in enamel supported by bonded amalgam. Microleakage
      was observed in 16% of the enamel-amalgam interfaces, 10% of the dentin-amalgam
      interfaces, 7% of the amalgam-composite interfaces, 4% of the composite-enamel
      interfaces and 11% of the composite-dentin interfaces. CONCLUSIONS: Bonded
      amalgam appears to be as effective as bonded composite in supporting undermined
      enamel in terms of resistance to fracture, but composite may have better marginal
      adaptation to enamel compared to bonded amalgam. Good marginal adaptation may be
      observed between amalgam and composite in composite-amalgam restorations.

PMID- 9922613
TI  - Fluoride release from orthodontic bonding agents: a comparison of three in vitro
      models.
AB  - The aim of this in vitro study was to compare fluoride release from two cement
      disc models (partially varnished and unvarnished) of three orthodontic bonding
      materials with fluoride release from the same materials when used to bond an
      orthodontic bracket onto a tooth surface. A resin-modified glass ionomer cement
      (Vitremer) and a compomer material (Dyract Ortho) were compared with a
      conventional resin adhesive (Right-On). Ten discs (3.0 mm diameter and 1.5 mm
      thick) of each material were manufactured in a silicone mould and ten premolar
      teeth were bonded with orthodontic brackets using each material. All the premolar
      teeth were covered with nail varnish up to the bracket periphery and five of the
      discs for each material were coated with nail varnish on both upper and lower
      surfaces which halved the surface area. The fluoride released into 2 ml of
      deionised water, from each tooth or disc, was measured at regular intervals over
      60 days. At 60 days, cumulative fluoride release was highest from the unvarnished
      discs, less for the varnished discs and least from the tooth-bracket model for
      both test materials. Despite having twice the surface area, the unvarnished disc
      model released only 1.2 to 1.5 times more fluoride than the varnished disc model.
      Compared with the tooth-bracket model, the unvarnished discs released 3.0 to 4.5
      times more fluoride, whereas the varnished discs released only 2.2 to 3.7 times
      more fluoride. For the materials tested in this study, halving the surface of the
      discs did not reduce the cumulative fluoride release by half. The tooth/bracket
      model with minimal bonding material demonstrated substantial cumulative fluoride
      release. The pattern of fluoride release was similar for all models tested.

PMID- 9922614
TI  - The influence of dentine bonding systems and their handling characteristics on
      the morphology and micropermeability of the dentine adhesive interface.
AB  - OBJECTIVES: Development of an adequate interfacial seal is fundamental to
      achieving a good dentine bond. This study investigates the influence of the
      properties and application of primers and resin adhesives on dentine interfacial
      morphology and micropermeability, using a fluorescence confocal microscopy
      technique. METHODS: Three commercially available (Optibond, Clearfil Liner Bond
      2, Pertac Universal Bond) and four experimental dentine bonding systems based on
      the total each technique were used in the study. Approximal cavities were
      prepared in third molar teeth and restored using the dentine bonding system (DBS)
      and resin composite. In the interfacial morphology study the primer and adhesive
      bonding system were labelled with fluorescent dyes, while in the
      micropermeability study the pulp chambers were filled with fluorescent labelled
      saline for 3 h. Ten teeth were prepared in each study for each dentine bonding
      system. Teeth were sectioned longitudinally and viewed with a tandem or laser
      scanning confocal microscope. Interfacial micropermeability from the pulpal wall
      was measured using image analysis techniques. RESULTS: All primers and adhesives
      showed good penetration of the prepared dentine, except Pertac Universal Bond
      which manifested 100% micropermeability. The lowest micropermeability results
      were obtained with Clearfil Liner Bond 2, Optibond and a total etch experimental
      system where the primer was applied with agitation and contained no photo
      initiators and the adhesive resin was unfilled. The latter, when used with a
      photosensitive version of the same primer, demonstrated a detrimental effect on
      micropermeability. Light activation of primers in the experimental systems
      coincided with very variable patterns of leakage. CONCLUSIONS: This high
      resolution confocal fluorescence technique enabled both the degree and site of
      micropermeability within the interfaces to be recorded. Matching of primers and
      adhesives in DBS is important to minimize micropermeability. The non-polymerized
      primer system probably retained some elasticity in the hybrid zone and so gave
      less leakage than experimental primers with photo-initiators.

PMID- 9922615
TI  - Aluminium radiopacity standards for dentistry: an international survey.
AB  - OBJECTIVE: The aims of this study were to determine the appropriate composition
      and purity limits of aluminium alloy radiopacity standards for dental
      biomaterials, taking into account the current status in representative
      laboratories worldwide, and to formalise the calculation procedure for processing
      radiopacity data. METHODS: A series of aluminium step-wedges were obtained from
      academic and industrial research laboratories. These were analysed by energy
      dispersive X-ray procedures. The set of step-wedges were independently
      characterised for radiopacity at two University dental schools. RESULTS: The
      percentage of aluminium together with the percentages of minor alloying elements
      (magnesium, manganese, iron and silicon) have been determined as mass
      percentages. For each centre, the optical density versus step-height for all
      wedges was judged to fall on a common curve, with the main exception of one step
      wedge that was found to contain 4% copper, by mass. A suitable calculation
      procedure was described explicitly. CONCLUSION: Of the examined representative
      step-wedges, all but the aluminium--4% copper material were satisfactory and gave
      results comparable with wedges of high purity. Limits should therefore be revised
      for composition of aluminium radiopacity step-wedges or test blocks to a more
      realistic level of purity. Alloys with more than 0.05% copper or 1.0% iron should
      be excluded and the aluminium content should be at least 98% by mass. In the
      calculations deployed for deriving radiopacity as 'equivalent aluminium
      thicknesses', an appropriate linear regression procedure should be employed and
      considerable care taken in the evaluation of materials of low or borderline
      radiopacity, relative to specification limits. The method described is
      principally suitable for materials with radiopacity greater than 1 mm. For
      materials with radiopacity less than 1 mm aluminium, thicker specimens (2 mm)
      should be used.

PMID- 9922616
TI  - Water resistance of resin-bonded joints with time related to alloy surface
      treatment.
AB  - OBJECTIVES: This paper attempts to study the resistance of resin-bonded metallic
      joints to damage in water with time. METHODS: Unlike the shear or tensile test, a
      cleavage test (Double Cantilever Beam test) allows us to follow the crack
      propagation in water, according to the fracture mechanics concept. Moreover, it
      is possible to follow the kinetic degradation of the metal/resin interface
      because this test is not totally destructive to the assembly. We have worked on
      18 batches according to the nature of the alloys (Pd, Pd-Ag, Au, Co-Cr and Ni-Cr)
      and the surface treatment (sandblasting, Silicoater MD, Rocatec, V-Primer). The
      crack length was measured over a period of 20 days. The results are expressed in
      terms of adherence energy. RESULTS: The adherence energy dramatically decreased
      with time in water. The slope of the regression straight line appears to be a
      good criterion for evaluating the durability of the alloy/adhesive interface. We
      have demonstrated the importance of silica coating and, especially, the
      effectiveness of the Rocatec system upon the degree of hydrolytic degradation,
      and have shown how the development of cracks depends upon surface treatment.

PMID- 9922617
TI  - The sham of saving social security first.

PMID- 9922618
TI  - Health care reform and public health: a paper on population-based core functions.
      The Core Functions Project, U.S. Public Health Service, 1993.

PMID- 9922619
TI  - Welfare reform and women's health: review of the literature and implications for
      state policy.
AB  - In August 1996, the Personal Responsibility Work Opportunity Reconciliation Act
      (P.L. 104-193) was signed into law, ending a 60-year federal entitlement
      guaranteeing families some basic level of assistance during periods of economic
      hardship. Several components of this new legislation have the potential to impact
      upon the health and well-being of women and children. We summarize studies
      examining the relationship between welfare participation and physical and mental
      well-being of women and what is known about the effects of poverty on health; the
      patterns of employment among welfare participants and the health consequences of
      low-wage work on women; domestic violence among welfare recipients; the potential
      health consequences of the provisions of the new Temporary Assistance to Needy
      Families (TANF) program for women's and adolescent health; and the consequences
      of the new TANF provisions for the health and well-being of immigrant women. We
      discuss the implications for policy makers in monitoring and minimizing the
      negative impact of welfare reforms on women's health and well-being.

PMID- 9922620
TI  - Pro-drinking messages and message environments for young adults: the case of
      alcohol industry advertising in African American, Latino, and Native American
      communities.
AB  - This paper examines targeted alcohol advertising in three ethnic communities:
      African Americans, Latinos, and Native Americans in the U.S. We focus on the
      appropriation of cultural systems and the reinvention of them as commodities to
      consumers. We outline the specific strategies used in each ethnic community. For
      African Americans, there is an emphasis on selling malt liquor to young adults
      through the use of "power" and gang-related images. For Latinos, there is an
      appropriation of historical and cultural symbols such as the national flags and
      maps of Mexico and Central America. Native Americans have coalesced to keep the
      image of a chief and warrior, Crazy Horse, from being used to market malt liquor.
      Each of the ethnic groups is engaged in action to prevent alcohol-related
      problems in their communities. Generating and implementing solutions is a
      universal social responsibility.

PMID- 9922621
TI  - Does cigarette print advertising adhere to the Tobacco Institute's voluntary
      advertising and promotion code? An assessment.
AB  - OBJECTIVES: This investigation examined whether, despite the Tobacco Institute's
      Voluntary Cigarette Advertising and Promotion Code, current cigarette print
      advertising communicates culturally positive messages to youth about smoking.
      METHODS: Nine hundred thirteen students in grades 6-8 (ages 10-15) were shown a
      sample of four contemporary cigarette print ads (Camel, Marlboro, Newport, and
      Virginia Slims) and completed structured written assessments designed to capture
      their perceptions of each ad. RESULTS: Across the four ads, between 37% and 84%
      of the students reported that the ads communicated to them that smoking will make
      people popular, cool, successful in life, sexy, attractive, and healthy. Sizeable
      percentages of students reported that the ads show people using the product in an
      "exaggerated" way, and that what people in the ads are doing requires "exercise
      and physical energy." The median estimated age of the models in the ads was under
      age 25 for four out of the six models. CONCLUSIONS: As perceived by adolescents,
      current cigarette print advertising violates basic tenets of the Voluntary Code,
      thus bringing into question the tobacco industry's ability to self-regulate image
      advertising. These findings suggest that the FDA ruling to prohibit image
      advertising for tobacco in publications with significant youth readership
      deserves serious consideration.

PMID- 9922622
TI  - Trade Related Aspects of Intellectual Property Rights (TRIPS) and the threat to
      patients: a plea for doctors to respond internationally.
AB  - Many recent international agreements sponsored by bodies such as the World Trade
      Organisation (WTO), aim to facilitate the global free flow of goods, services and
      capital, by opening markets under the threat of trade sanctions. Nation States
      signing such agreements, in particular the Trade Related Aspects of Intellectual
      Property Rights (TRIPS), agree to suffer a sovereignty deficit in order to
      enhance their trading prospects. In the resulting reorganization of trade,
      medicine may be marginalised as merely another industry that must open its
      regional doors in the interests of global corporate productivity. We make a plea
      for medical organizations to lobby in appropriate international forums to create
      "hard" norms that ensure such international trade agreements that adequately
      respect the demands of fundamental ethical principles of the doctor patient
      relationship, principles such as medical loyalty and beneficence.

PMID- 9922623
TI  - Ethical dilemmas in the use of donor gametes.
AB  - Current ethical debate is about the processes of reproductive medicine; the moral
      status of the embryo. Within a societal acceptance of the expansion of
      reproductive medicine worldwide, donated gametes are increasingly being used.
      Medical practice favours anonymity of donors and confidentiality for
      participants. These apparently legitimate concerns are to protect the adults
      involved. They do not address the implications for any children thus created.
      This paper aims to shift the debate and to address specifically the rights and
      needs of the children following gamete donations. How far do they need to know
      about their birth origins? How do they fare as future adults with no knowledge of
      50% of their genetic family histories? Data is now available about how children
      themselves view this and, in accord with international declarations about the
      rights of the child, a radical new approach is urgently needed both in
      reproductive medicine and legal provisions.

PMID- 9922624
TI  - Towards a universal definition of the right to health?
AB  - Despite the fact that the right to health is solidly embedded in various
      international human rights documents, there remains widespread confusion about
      the precise meaning of this right and its legal ramifications. It is widely
      believed that the absence of a universal definition, together with the lack of
      clarity about the nature and scope of corresponding State obligations, impede
      States from realising the aspirations enshrined in the right to health. In fact,
      conceptual unclearness is also likely to discourage national judges and treaty
      monitoring bodies from critically measuring--and if necessary, enforcing--State
      compliance and to deter Non-Governmental Organizations (NGO'S) from using the
      existing national and international system to monitor compliance, to report
      violations and to engage in other activities typically performed by human rights
      advocacy groups. This article seeks to articulate the meaning of the right to
      health, by focusing on its core content and the obligations thought to be
      inherent to this right. Attention will also be paid to the need to design
      accurate human rights indicators to document and analyse trends. A call is made
      for the adoption of a special General Comment on the right to health, not only to
      enable States Parties to the International Covenant on Economic, Social and
      Cultural Rights to better pursue their obligations, but equally to incite more
      academic discussion, to draw the interest of human rights NGO'S and, last but not
      least, to do justice to a right which is intimately related to human dignity, the
      concept underlying all human rights.

PMID- 9922625
TI  - The sensitivity of forensic tests for rape.
AB  - The objective of this study is to provide an overview of the types of forensic
      evidence gathered during clinical examinations in cases of sexual assault, and to
      review the literature regarding the sensitivity of individual procedures. The
      methodology involved a computerized literature search of the MEDLINE, PsycINFO,
      Cinahl and HealthStar databases from 1992 to 1996, and a secondary search
      involving consultation with local facilities and manual searching of reference
      lists. Based on our review, the chance of finding positive evidence is largely
      time-dependent, particularly regarding sperm and seminal products, which are
      weighted most heavily in rape investigations. The best chance of recovering
      seminal evidence is most frequently stated as being less than 50%, with far lower
      chances after 24 hours. Specific tests such as pubic hair combing would not be
      expected to yield evidence in more than 4% of cases. That test, while of low
      sensitivity, is at least not as invasive as some of the others. More invasive
      tests, such as sampling from the rectal cavity, yield positive sperm findings in
      fewer than 2% of cases. The importance of ensuring that those working in the
      field of sexual assault understand that no positive finding on forensic tests
      does not mean that no attack occurred is highlighted. Medico-legal implications
      are discussed and suggestions for future research initiatives are highlighted.

PMID- 9922626
TI  - Medical confidentiality and detainees.
AB  - A doctor who is asked to see a detainee may be one (or both) of the following;
      (i) a treating clinician and (ii) a gatherer of forensic evidence. This dual, and
      sometimes overlapping role can give rise to conflicting ethical and legal duties
      of great complexity. In the UK, the prosecution is obliged under common law to
      disclose to a defendant all "unused" material obtained as potential evidence
      during an investigation. In keeping with this, police surgeons are asked to
      disclose, as a matter of routine, a full set of their clinical records, whether
      or not the detained patient has given consent. This legal requirement conflicts
      with the ethical constraints placed on all doctors registered with the UK's
      General Medical Council. The UK Parliament has debated a new law which helps
      resolve the conflict in favour of maintaining medical confidentiality for
      detainees.

PMID- 9922627
TI  - Induction, identification or folie a deux? Psychodynamics and genesis of
      Munchausen syndromes by proxy and false allegations of sexual abuse in
      adolescents.
AB  - When dealing with Munchausen syndrome by proxy as well as with false allegations
      of sexual abuse, we normally were confronted with complex family dynamics
      especially between mother and child. To date there are no scientific discussions
      on the importance of these dynamics for the development of manifest symptoms in
      the child and regarding the child's contribution. The descriptions of the
      Munchausen syndrome by proxy stressed the maternal pathology from which the
      child's symptoms seemed to be derivable by the concept of simple induction.
      Regarding false allegations of sexual abuse, especially in divorce proceedings,
      even publications on the motives of the inducing parents were rare. This paper
      presents considerations on the object relation dynamics as well as on the
      intrapsychic dynamics of the children and adolescents in question. Related
      forensic psychiatric problems are discussed.

PMID- 9922628
TI  - Perceived coercion related to psychiatric comorbidity and locus of control in
      institutionalized alcoholics.
AB  - One-hundred and four alcoholics, 73 men and 31 women, were treated at Karlsvi
      Rehabilitation Center between November 1990 and December 1992. Fifty-eight
      subjects were compulsorily treated and 46 voluntarily treated. Experiences of
      negatively perceived coercion were assessed in the beginning of treatment and at
      discharge after 5-6 months by using the semi-structural interview according to
      Eriksson-Westrin. Locus of control was measured by using the Swedish version of
      the Rotter-scale for external/internal attribution. Axis I psychiatric
      comorbidity was assessed according to the Structural Clinical Interview, DSM-III
      R (SCID). Ninety-one percent of the compulsorily committed and 56% of the
      voluntarily admitted subjects reported violations of integrity or negatively
      perceived coercion during treatment (p < 0.001); women to a higher extent than
      men (93%/70%, respectively; p < 0.01). At the discharge interview 87% of the
      compulsorily treated subjects and 52% of the voluntarily treated subjects still
      reported that the coercive experiences were wrong or violating to personal
      integrity. Female subjects were less inclined to justify earlier reported
      coercive examples than male subjects (0%/8%, respectively; p < 0.05). Coercive
      implementation fait accompli was reported in 70%, persuasion in 21% and threat in
      9% of the cases. No experiences of force were reported. Subjects with an internal
      locus of control reported negatively perceived coercion to a higher extent than
      subjects with an external locus of control (84%/22%, respectively; p < 0.001).
      Internally oriented subjects were also less inclined to justify the coercive
      experiences at the discharge interview than externally oriented subjects (2%/14%,
      respectively; p < 0.01). Prevalence of psychiatric comorbidity was high (78%).
      Reports of negatively perceived acts of coercion and locus of control were
      unrelated to psychiatric comorbidity. Sixty-seven percent of the subjects were
      homeless. Homelessness was unrelated to locus of control, coercive reports and
      psychiatric comorbidity.

PMID- 9922629
TI  - Forensic psychiatric service in Israel: ten years experience in an in-patient
      hospital unit.
AB  - In 1991 legislators revised the Mental Health Act in Israel, placing
      responsibility for forensic psychiatric evaluations with the district
      psychiatrist. The aim of the present paper is to describe the changing patterns
      of the forensic service in Israel's largest psychiatric hospital in the light of
      changing legislation. In the last 15 years a psychiatric forensic team provided
      evaluations both in an ambulatory clinic and a special in-patient ward. All
      medical records of subjects referred for forensic evaluations between 1982-1992
      were re-examined. Demographic, forensic and psychiatric data were recorded.
      During this period the service experience a 15% increase in the number of
      evaluations. The team tended to prefer ambulatory evaluations. During the latter
      part of the period studied more referrals were with a previous criminal record
      and less with a history of mental disorders. An increase in drug and sex crimes
      was noted with a corresponding decrease in property and financial offences.

PMID- 9922630
TI  - Pharmaceutical regulation in the single European market.
AB  - This paper assesses the impact of new EU-wide drug authorisation procedures. The
      paper examines various attempts to introduce harmonised market authorisation
      routes for pharmaceuticals including the establishment of the multi-state,
      concentration, decentralised and centralised procedures. The paper considers the
      current role of the European Medicines Evaluation Agency and the likelihood that
      its powers will be increased in the future. Finally, the paper assesses whether
      EU regulation has created beneficial market conditions for pharmaceutical
      companies operating in the single European market.

PMID- 9922631
TI  - Informed consent for medical interventions under Turkish law.
AB  - Free and informed consent of the patient is the prerequisite of any medical
      intervention under Turkish law. "Information" comprises the purpose, nature,
      consequences and risks of intervention. "Intervention" is understood in its
      widest sense. The patient has the right to withdraw his consent freely at any
      time. For the patients under age (18 years) or incapacitated persons, informed
      consent is given by the legal representative (parents or guardian). In emergency
      situations, including abortion and sterilization, the practitioner may intervene
      for the benefit of the patient without consent. Furthermore, for purposes of
      treatment of addicts, and in cases of epidemic diseases medical intervention may
      be carried out without consent for health reasons and public safety. The right to
      be informed or not about health and intervention is a patient's personal right.
      These rights are bound strictly to the personal right of the patient.
      Disregarding these rights can cause legal liability of the physician. The
      previous wishes of the patient and the right to refuse treatment of the patient
      must be respected. Legal representatives of minors or incapacitated patients may
      not refuse treatment on their behalf. Treatment without consent or without
      informed consent is a "medical malpractice."

PMID- 9922632
TI  - Research and trade in genetics: how countries should structure for the future.
AB  - This article discusses the international trade issues that will underlie the
      institution of genetic research and technological regimes. As the biotechnology
      industry grows trade considerations will become paramount in structuring domestic
      regimes designed to limit or emphasise certain aspects of genetic research. As
      such, many countries will wish to maintain or enhance their comparative economic
      and strategic advantages vis-a-vis their trading partners. The international
      biotechnology climate will mature within the next fifteen to twenty years.
      Consequently, there will be an impetus towards conducting a multilateral trade
      round on genetic research and technology. The supposition is that this future
      trade round will be similar to the intellectual property negotiations at the
      Uruguay Round of the GATT. Countries that are willing to adopt regimes that are
      very conducive to genetic research will be better placed for the future.

PMID- 9922633
TI  - From make believe to doomsday eve: or should we patent genes?
AB  - Patenting genes and its consequences and justifications in the context of law and
      ethics is a particularly controversial issue, with the potential to affect every
      aspect of our lives. If only a decade ago it seemed merely fiction that
      biotechnology would lead to inventions and progress beyond our imaginations,
      today, we have come to realize that this phenomenon--the art of make-believe--is
      close to becoming reality. In order to establish legal means to control these
      inevitable advances, and prevent a doomsday scenario from becoming fact, this
      paper is aimed at discussing, on the philosophical level, the contradicting moral
      and ethical concerns and justifications of the patenting of genes as well as
      accompanying environmental, constitutional and religious arguments. In order to
      better understand the arena of gene patenting, this paper commences with a brief
      introduction to the property debate of who owns human organs in general, and
      genes in particular. Its target is to confront us with the dilemmas arising in
      this field, as a starting point for finding legal solutions to override the gap
      presently existing, when science sets the rules and law is lagging behind.

PMID- 9922634
TI  - The right to die and physician-assisted suicide medical, legal, and ethical
      aspects (Part I).
AB  - Part 1 of this paper examines the issue of the "Right to Die", and its
      relationship to the discipline of Bioethics and the doctrine of Informed Consent.
      The discussion underlines the role and rights of the patient. A number of
      relevant judgments are quoted, with their implications. Part 2, to be published
      in our next issue, continues the discussion, with emphasis on the subject of
      physician-assisted suicide and the activities of Dr. Kevorkian. Further legal
      cases are quoted with relevant analysis, together with proposed legislation under
      the title "Death with Dignity". Finally, the author points to possible future
      developments in this controversial issue.

PMID- 9922635
TI  - Edward Lyman Munson, M.D.: a biographical study in military medicine.

PMID- 9922636
TI  - Military women's research.
AB  - Until 1994, there was a paucity of research aimed at the female soldier. With the
      dramatic increase in the numbers of military women and their subsequent
      assumption of expanded roles, it is vital that increased research emphasis be
      exerted toward this group. A 1994 Congressional directive mandated that women be
      included in all Department of Defense-sponsored research. This led to the
      establishment of the Defense Women's Health Research Center for
      "multidisciplinary and multi-institutional research" on military women's health
      issues. This article presents demographic data of military women along with
      descriptions of current research endeavors and issues in need of continued and
      future research.

PMID- 9922637
TI  - Female circumcision: the prevalence and nature of the ritual in Eritrea.
AB  - This study evaluates the prevalence, complications, and attitudes concerning the
      practice of female circumcision among the women of Eritrea. Four hundred thirty
      six Eritrean women from rural and urban environments were questioned about their
      perceptions and beliefs concerning female circumcision. Eighty-eight percent of
      those interviewed had undergone some form of female circumcision. Those who
      favored the continuation of the practice were more likely to be rural dwellers
      with little formal education, and they did so primarily out of tradition or
      cultural conformity. The direct and indirect consequences of this practice to the
      health of women and infants are considerable and as complex as the social,
      religious, and traditional factors that have led to its preservation.

PMID- 9922638
TI  - Epidemiology of illness and injury among U.S. Navy and Marine Corps female
      training populations.
AB  - Evidence suggests that female military populations are at greater risk than their
      male counterparts for certain training- and combat-related illnesses and
      injuries. The objective of this prospective, multisite, epidemiological study was
      to define the patterns of illness and injury in military women during training.
      We developed a computer-based outpatient tracking system for prospective data
      collection of all outpatient encounters for use at (1) Officer Candidate School
      (OCS), Quantico; (2) Marine Corps Recruit Depot (MCRD), Parris Island; and (3)
      Recruit Training Command (RTC), Great Lakes. During the study period, 85.8% of
      OCS candidates (260 of 303), 72.4% of MCRD recruits (2,002 of 2,766), and 83.4%
      of RTC recruits (7,395 of 8,865) had at least one medical encounter during
      training. The most common category of medical encounters at all three sites was
      musculoskeletal injury, followed by respiratory and dermatological disorders.
      This study establishes high morbidity rates and identifies medical priorities for
      preventive interventions in Marine Corps and Navy female trainees.

PMID- 9922639
TI  - Wellness intervention with pregnant soldiers.
AB  - The purpose of this study was to measure the effects that wellness program
      intervention for pregnant soldiers, exercise and/or education, had on methods of
      delivery, pregnancy outcomes, rates of complications, Army Physical Fitness Test
      scores, and labor and delivery costs. The study consisted of a retrospective
      review and analysis of 823 active duty Army obstetric and newborn records, 181
      Army Physical Fitness Test records, and 411 initial and 148 postpartum subjective
      questionnaires. Data were collected from records of soldiers who delivered at
      Madigan Army Medical Center (Tacoma, Washington) between January 1992 and
      December 1994. Group I (N = 211) included soldiers who received wellness
      intervention, group II (N = 147) included those who did not receive wellness
      intervention. Limited data from the records of soldiers who delivered before a
      wellness program was offered on post constituted group III, a historical control
      group (N = 413). Group IV included data from a high-risk population (N = 52)
      collected during the wellness program. Data were also divided into additional
      subgroups to ascertain if one aspect of the wellness program (i.e., exercise
      versus education) influenced any or all of the dependent variables. A soldier's
      data were excluded if a pregnancy was terminated before 20 weeks of gestation or
      if it was a multiple gestation. Demographic data and variables were compared
      using multivariate methods of analysis to evaluate the effect of the independent
      variable, wellness intervention. Results indicated that infants of the wellness
      group participants had proportionately increased gestational age and birth
      weight, with reduced incidence of the complications fetal bradycardia,
      hyperbilirubinemia, preeclampsia, and premature labor. Likewise, African-American
      female soldiers in this study, assessed in other studies as a high-risk group,
      had a lower incidence of premature delivery and low birth weight when they
      participated in wellness intervention. Of clinical interest, it appeared as
      though wellness intervention shortened labor duration and reduced the number of
      neonatal intensive care unit admissions and the number of neonatal intensive care
      unit days, which resulted in reduced health care costs.

PMID- 9922641
TI  - The management of endodontically treated teeth using a Computer-Aided Design and
      Computer-Assisted Manufacturing/Computer-Aided Design and Computer-Integrated
      Manufacturing system.
AB  - This article introduces a new approach for restoring endodontically treated
      posterior teeth. Significantly reduced natural tooth structure often remains not
      only because of previous restorative measures but also because of endodontic
      procedures. Cast restorations for these teeth are almost universally recommended.
      The exception to this is the rare instance in which only conservative endodontic
      access openings exist in teeth presenting with no former existing restorations.
      Typically, multiple clinical appointments are required to complete the final cast
      restoration. This article presents Computer-Aided Design and Computer-Assisted
      Manufacturing/Computer-Aided Design and Computer-Integrated Manufacturing
      applications for restorative dentistry that provide the necessary care in an
      expeditious manner.

PMID- 9922640
TI  - Spouse abuse: physician guidelines to identification, diagnosis, and management
      in the uniformed services.
AB  - Spouse abuse is a major social issue in our country. Based on national samples,
      between 10 and 20% of couples report some type of violence during the course of
      their marriage. In the United States, 1.8 million women are physically abused by
      their spouses each year. Within the military, it is estimated that the incidence
      of spouse abuse is even greater than in the civilian sector. Estimates suggest
      that one-third of military spouses experience abuse during their marriage.
      Although 87% of women prefer discussing their victimization with their physician,
      physicians, as a group, have been least effective in helping them. Recently,
      several barriers to physician recognition and intervention in domestic violence
      have been identified, and recommendations for specific training on abuse have
      been published. This paper provides military physicians an in-depth review of the
      guidelines to identification, diagnosis, and management of spouse abuse, with a
      special emphasis on their implementation within the uniformed services.

PMID- 9922642
TI  - Parachuting injuries during Operation Royal Dragon, Big Drop III, Fort Bragg,
      North Carolina, May 15/16, 1996.
AB  - On the night of May 15/16, 1996, the largest parachute assault of United States
      (US) and United Kingdom (UK) airborne forces in 52 years occurred at Fort Bragg,
      North Carolina. This paper describes the injuries sustained in that operation. A
      total of 4,754 (US, N = 3,066; UK, N = 1,688) aircraft exits were made, causing a
      total of 137 (US, N = 73; UK, N = 64) injuries in 117 personnel (US = 68; UK =
      49). There were 15 hospital admissions (US = 8; UK = 7; p = 0.37) and no
      fatalities. The combined exit injury incidence was 24.6 injured soldiers per
      1,000 exits. The US exit injury rate was 22 injured per 1,000 aircraft exits and
      the UK rate was 29 injured soldiers per 1,000 aircraft exits. This difference was
      not statistically significant (p = 0.25). Lower extremity sprains, strains, and
      fractures accounted for the majority of injuries in US and UK forces. UK soldiers
      sustained significantly more of these potentially incapacitating injuries than US
      troops, 16.1 per 1,000 exits versus 9.1 per 1,000 exits, respectively (chi 2 =
      4.07; p = 0.043; relative risk [RR] = 1.70; 95% confidence interval [CI] = 1.01,
      2.86). The UK forces sustained significantly more closed head injuries than US
      forces, 7.1 per 1,000 exits versus 2.3 per 1,000 exits, respectively (chi 2 =
      6.4; p = 0.011; RR = 3.13; 95% CI = 1.23, 7.93). The UK forces also had
      significantly more soldiers with multiple injuries than US forces (RR = 9.15; 95%
      CI = 2.5, 39.7). Factors that may have influenced differences in injury incidence
      include differences in weight of personal equipment and possible differences
      between the drop zones.

PMID- 9922643
TI  - Wartime amputations.
AB  - This paper outlines the causative factors, incidence, and localization of
      extremity amputations of wounded persons treated at the Osijek University
      Hospital (Eastern Slavonia) during 1991 and 1992. The medical documentation of
      5,024 patients was analyzed. Of these, 1,560 patients were treated in the
      hospital (31.0%). A total of 1,916 extremity injuries were found in hospitalized
      wounded patients. Injuries of the lower extremities were found in 1,226 patients
      and injuries of the upper extremities in 690 patients. Gunshot-explosive
      fractures of the extremity bones were diagnosed in 1,122 patients (71.9%): 735
      (47.1%) in the lower extremities and 387 (25.8%) in the upper extremities. In 90
      cases (4.6%), amputation of the extremities (including the fingers) using an open
      circular or flap technique was performed. Large amputations (above the wrist and
      ankle joints) were performed on 40 patients (2.6%). Amputation of the upper
      extremities was performed on 53 patients (58.9%), and amputation of the lower
      extremities was performed on 37 patients (41.1%). Injuries of the major blood
      vessels were treated with primary reconstruction in the upper extremities in 44
      patients and in the lower extremities in 96 patients. Unstable gunshot-explosive
      fractures of the long bones were stabilized with external fixation, and fractures
      of the short bones were stabilized by means of minimal osteosynthesis or external
      fixation. Secondary amputations (on the lower extremities) were performed on 2
      patients because of vascular insufficiency. Not a single secondary amputation
      procedure was performed because of infection, secondary uncontrolled hemorrhage,
      or gas gangrene. Amputation is a radical and irreversible intervention, and
      indications for amputation must be determined by those with great surgical
      experience and good knowledge of military-surgical doctrine.

PMID- 9922644
TI  - Primary trauma care experience of army reserve combat medics: is a new approach
      needed?
AB  - Combat medics play a significant role in any fighting unit. In recent years,
      during times of peace and low-intensity military conflicts, as well as in
      operations other than war, reserve combat medics have been challenged to treat
      major casualties in the field. Although this work requires important manual
      skills, the medics perform basic treatment maneuvers that are not necessarily for
      saving of lives. A sample survey of reserve combat medics revealed that most
      (70%) were engaged in medical care for trauma victims during their regular and
      reserve service. Many (32.5%) were involved in incidents with multiple
      casualties. These incidents included seriously injured victims, with 39.2% of the
      medics being involved with air evacuation and 44.4% with fatalities. Not all
      medics are exposed to major trauma, but for those who are, the numbers of
      patients per medic is not large. Therefore, the need to educate the medics in
      cognitive, and more importantly, in manual skills, is obvious. Suggestions for
      the means to do so are provided.

PMID- 9922645
TI  - An examination of body weight standards and the association between weight and
      health behaviors in the United States Air Force.
AB  - This study examined the weight standards used by the U.S. Air Force and tested
      whether Air Force personnel who exceed the maximum allowable weight standard are
      more likely to engage in health risk behaviors compared with individuals who do
      not exceed current Air Force weight standards. Participants were 32,144
      individuals who completed basic military training from August 1995 to August
      1996. Compared with body mass levels known to predict increased health risks, the
      Air Force maximum allowable weight standards were found to be more stringent for
      women than for men. Furthermore, exceeding the maximum allowable weight standard
      of the weight management programs did not consistently indicate that an
      individual engaged in a less healthy lifestyle than other airmen. Perhaps other
      risk factors, such as cigarette smoking, may be more closely linked to negative
      health consequences than body weight.

PMID- 9922646
TI  - Stability of trimedoxime in concentrated acidic injectable solutions.
AB  - The degradation of trimedoxime in concentrated (114 mg/ml) acidic solutions was
      studied at several temperatures in the pH range 3.0 to 4.3. The degradation
      profile showed a relationship indicative of first-order kinetics. Trimedoxime was
      found to be stable in the pH range 3.0 to 3.8, with maximum stability at pH 3.0.
      The activation energy of the hydrolysis reaction at pH 3.0 was found to be 19.4
      kcal/mol, and the half-life was 124 years. General equations were derived
      relating the half-life of trimedoxime solution to pH and temperature. The t90
      value at 25 degrees C was calculated for each pH value studied and was found to
      be 11 to 18 years within the pH range 3.0 to 3.8.

PMID- 9922647
TI  - Delayed unilateral post-traumatic tremor: localization studies using single
      proton computed tomographic and magnetic resonance spectroscopy techniques.
AB  - We present the case of a 46-year-old former U.S. Marine who developed unilateral
      dystonic tremor responsive to anticholinergic medications 13 years after
      contralateral, combat-induced head trauma. Although conventional neuroimaging
      techniques showed normal brain anatomy, single-proton computed tomographic scans
      demonstrated hypometabolism ipsilateral to the area of old trauma. Proton
      echoplanar spectral imaging demonstrated decreased signal in this same area on
      creatine imaging, which normalized on anticholinergic medication. Choline imaging
      on medication showed a signal void in the clinically suspected basal ganglia
      thalamus region. We believe that these results indirectly suggest a trans
      synaptic origin of the patient's movement disorder.

PMID- 9922648
TI  - Road rash with a rotten odor.
AB  - As military physicians, our mission is to support the fighting force and keep our
      soldiers mission capable. One group of disorders that can quickly cripple a
      fighting force is disorders of the foot. A complete survey of dematologic
      conditions of the foot is quite extensive, but only one comes with its own
      distinctive odor. This foul rash is pitted keratolysis.

PMID- 9922649
TI  - Acute intracranial boxing-related injuries in U.S. Marine Corps recruits: report
      of two cases.
AB  - Serious acute intracranial injuries from boxing are a recognized, albeit rare,
      event. Acute brain injuries such as concussion, hemorrhage, and contusion are
      easily recognized because of their rapid onset of neurological impairment. The
      sequelae of such injuries range from transient diminished cognitive function to
      irreversible brain damage and, on occasion, death. The more serious injuries are
      certainly minimized as a result of regulatory policy, improved medical awareness,
      and the use of safety equipment. The incidence of serious acute head injury in
      amateur boxing and noncompetitive boxing is lower than that found in the
      professional ranks. Our survey of instructional boxing in U.S. Marine Corps basic
      training during an 8-year period detected only three serious acute brain injuries
      incurred by approximately 180,000 participants, equating to one serious head
      injury per 60,000 participants. Serious head injuries constituted an extremely
      small percentage (0.3%) of the approximately 1,100 total boxing-related injuries
      surveyed during the period. We present two cases of serious acute brain injury
      incurred during noncompetitive boxing skills instruction as a part of U.S. Marine
      Corps basic training. A review of the data leads us to conclude that the risk of
      serious head injury in a well-supervised, instructional boxing program is
      relatively minimal. In any case, we recommend that any boxing be appropriately
      supervised and that specialized trauma care and an adequate transport mechanism
      to secure that care be readily available.

PMID- 9922650
TI  - Hypnosis using a communication device to increase magnetic resonance imaging
      tolerance with a claustrophobic patient.
AB  - This is a case report of a patient who prematurely terminated two previous
      magnetic resonance imaging procedures because of his highly claustrophobic
      condition. The patient was induced into a hypnotic trance twice before his third
      magnetic resonance imaging examination and he was given posthypnotic suggestions
      for decreased anxiety and increased physiologic control. Using a communication
      device with headphones on the patient, he was induced into a trance as he entered
      the magnet. This patient was successfully able to cope with this procedure and
      reported great satisfaction with treatment.

PMID- 9922651
TI  - Psychotic symptoms in post-traumatic stress disorder.
AB  - Although many coexisting disorders have been reported with post-traumatic stress
      disorder (PTSD), little reference has been made to the presence of psychotic
      symptoms. Psychotic symptoms are not included in the Diagnostic and Statistical
      Manual of Mental Disorders IV or International Classification of Diseases 10
      diagnoses of PTSD. The hallucinations and delusions described here in two cases
      of PTSD were accompanied by psychotic symptoms. These symptoms clearly differ
      from flashbacks but have a strong symbolic relationship to the trauma, and they
      do not respond to antipsychotic drugs. The question is whether there are two
      separate diagnoses or if psychotic symptoms are an integral part of PTSD. More
      systematic studies are required to explore the possibility of changing the
      current classifications of PTSD to include a diagnosis of PTSD with psychotic
      features.

PMID- 9922652
TI  - Emergency medicine quiz. Clinched fist injury.

PMID- 9922653
TI  - The heartmate left ventricular assist system: first successful implantation in
      Missouri.
AB  - We report a case of the first successful implantation of the HeartMate left
      ventricular assist system as a bridge to heart transplant in the state of
      Missouri. Indications, technique of insertion, patient selection, outcomes and
      future applications are discussed.

PMID- 9922654
TI  - [Clinical tests in the study of pathophysiology of collagen diseases].

PMID- 9922655
TI  - [Approach to symptomatic diagnosis of collagen diseases].

PMID- 9922656
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -erythrocyte sedimentation, C-reactive protein and serum amyloid A protein].

PMID- 9922657
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -rheumatoid factor].

PMID- 9922658
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -antinuclear antibodies and anti-DNA antibodies].

PMID- 9922659
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -anti-topoisomerase I antibodies and anticentromere antibodies].

PMID- 9922660
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -anti-ribonucleoprotein antibodies].

PMID- 9922661
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -antineutrophil cytoplasmic antibodies].

PMID- 9922662
TI  - [Progress in clinical tests and the pathophysiological tests of collagen diseases
      -complement].

PMID- 9922663
TI  - [Progress in clinical tests and the pathophysiological study of collagen diseases
      -blood coagulation disorders].

PMID- 9922664
TI  - [Physiopathological and therapeutic study of collagen diseases based on results
      of clinical tests--role of prostaglandins].

PMID- 9922665
TI  - [Physiopathological and therapeutic therapy of collagen diseases based on results
      of clinical tests--disorders of lymphocyte signal transduction].

PMID- 9922666
TI  - [Physiopathological and therapeutic study of collagen diseases based on results
      of clinical tests--collagen diseases and human leukocyte antigens].

PMID- 9922667
TI  - [Physiopathological and therapeutic study of collagen diseases based on results
      of clinical tests--cytokines and cell adhesion molecules].

PMID- 9922668
TI  - [Animal models of collagen disease].

PMID- 9922669
TI  - [Progress in clinical tests and the physiopathological and therapeutic study of
      collagen diseases (discussion)].

PMID- 9922671
TI  - [Outbreak of diarrhea due to SRSV infection].

PMID- 9922670
TI  - [A case of chorea-ballism with bilateral lesion of the corpus striatum and
      hyperglycemia].

PMID- 9922672
TI  - [A case of adult endocardial fibroelastosis with favorable pregnancy outcome].

PMID- 9922673
TI  - [A case of Behcet's syndrome associated with esophageal ulcer].

PMID- 9922675
TI  - [Basic and clinical study of Chlamydia pneumoniae infections].

PMID- 9922674
TI  - [A case of myasthenia gravis caused by D-penicillamine therapy].

PMID- 9922676
TI  - [Ca+ metabolism in the sarcoplasmic reticulum and the role of ryanodine and IP3
      receptors in the nervous system].

PMID- 9922677
TI  - [Quality of life of patients with cardiovascular diseases].

PMID- 9922678
TI  - [New immunotherapy for patients with neoplasms using tumor antigens recognized by
      T lymphocytes].

PMID- 9922679
TI  - [And the deaf were able to hear. Cochlear implantation].

PMID- 9922680
TI  - [The Danish care of persons with hearing impairment. Medical-audiological
      aspects].

PMID- 9922681
TI  - [Antibiotic prophylaxis in adult critically ill patients in intensive care
      units].
AB  - OBJECTIVES: To determine whether antibiotic prophylaxis reduces respiratory tract
      infections (RTI) and overall mortality in an unselected adults intensive care
      population. SEARCH STRATEGY: Systematic literature search in peer-reviewed
      journals indexed in MEDLINE, examination of relevant proceedings of scientific
      meetings and personal contact with trialists. SELECTION CRITERIA: All randomised
      clinical trials (RCTs), published and unpublished, comparing different forms of
      antibiotic prophylaxis used to reduce RTIs and mortality in unselected adult
      intensive care units (ICUs) populations. DATA COLLECTION AND ANALYSIS: Out of the
      32 RCTs eligible for this review data have been extracted from published reports
      and then complemented with information provided by study investigators for 29
      trials. Data were available only from published reports in the remaining three
      RCTs. For each trial the following information has been sought: a) method of
      randomisation; b) use of blinding techniques; c) number of randomised patients;
      d) number of patients with RTIs; e) number of deaths; f) number of patients
      excluded from the published analysis; g) number of RTIs and number of deaths
      among excluded patients. Pooled estimates of treatment effects across trials have
      been calculated after grouping RCTs in two main, mutually exclusive, categories:
      a) 15 trials testing the effect of a combination of a topical and a systemic
      antibiotic against no prophylactic treatment; b) 17 trials where the experimental
      treatment was a topical antimicrobial preparation. Crude proportions of RTIs and
      mortality were used to calculate the overall treatment effect. We also computed
      the number of ICU patients who need to be treated in order to prevent one
      infection and one death. MAIN RESULTS: Overall 32 RCTs including 5639 patients
      were identified. Pooled estimates of the 15 RCTs (including 3273 patients)
      testing the effect of the topical and systemic antibiotic combination indicate a
      strong significant reduction of both RTIs (OR = 0.36, 95% CI = 0.30-0.43) and
      total mortality (OR = 0.80, 95% CI = 0.68-0.93). Five and 23 patients need to be
      treated to prevent one infection and one death, respectively, using this
      treatment. When data on the effect of the combination based on topical
      antimicrobials were pooled from the 17 available trials (including 2366 patients)
      a marked reduction on RTIs (OR = 0.57, 95% CI = 0.46-0.69) also emerged but no
      corresponding effect on overall mortality (OR = 1.01; 95% CI = 0.84-1.22) was
      found. CONCLUSIONS: After 15 years of clinical research this meta-analysis of 32
      RCTs shows that a regimen of antibiotic prophylaxis based on a combination of a
      systemic and topical antibiotic can reduce both RTIs and overall mortality in ICU
      patients in a way that is both statistically significant and humanly worthwhile.
      Over and above their personal opinions intensivists should take this evidence
      into account when defining their policies.

PMID- 9922682
TI  - [Endocrinology--toward the next century].

PMID- 9922683
TI  - [Methods in the evaluation of medical students].
AB  - The achievements of medical students are decisively dependent on the method of
      evaluation during their education. Frequent testing of these achievements by well
      defined (cross-specialized) problems (involving cases) enables the student to
      quickly correct own knowledge- or skills-deficiencies, while the relevance of the
      curriculum is further visualized. A differentiated panel of tests evaluates both
      the students individual study methods and her ability to make clinical inquiry,
      diagnoses and application of practical skills. An insufficient individual
      performance graded by known minimal specific standards entails a feedback session
      with a counsellor who pin-points defects in the student's knowledge and suggests
      methods for correction. This form of evaluation is expected to be costly, but is
      a necessity to improve the quality of the graduating medical students.

PMID- 9922684
TI  - [Cochlear implantation in children. The first Danish results].
AB  - The aim of this study is to review indication, technique and results of cochlear
      implant (CI) treatment with Nucleus CI-multi-electrode of the first ten children
      operated in Denmark (five children with congenital deafness and five with
      acquired prelingual deafness due to meningitis). In the literature, the
      importance of early referral and operation at the age 2-3 (4) years for
      congenital deafness and as soon as possible on suspicion of acquired deafness
      (meningitis) is stressed. A short survey of our indications, technique and
      rehabilitation is presented. The results of treatment after 11-44 months' use of
      CI are that one child has language almost matching age, four use words and short
      sentences accompanied by support signing, three have sound reaction and say
      single words without sentence building, but of these two children have only used
      CI for a very short time and are improving. Two meningitis sequelae cases had
      cochlear ossification, which made the implantation difficult. Both patients had
      to be operated, and one of them is not using the processor.

PMID- 9922685
TI  - [Perinatal audit in the county of Viborg 1994-1996].
AB  - The purpose of this article is to present the results of the perinatal audit in
      Viborg County during the years 1994-1996. The perinatal deaths in Viborg County
      were classified according to commonly used classifications in perinatal audit
      evaluations, and mortality rates were calculated according to international
      definitions and compared with data from the Danish National Birth Register, 1995.
      During 1994-1996 the perinatal mortality rate decreased from 9.4/1000 deliveries
      to 6.5/1000 deliveries and the neonatal mortality rate decreased from 3.2/1000
      deliveries to 2.4/1000 deliveries. The reductions were not statistically
      significant. No significant difference in mortality rates between Viborg County
      and overall national mortality rates in 1995 was shown.

PMID- 9922686
TI  - [Predictors of sudden death and death from heart failure in patients with heart
      insufficiency are different].
AB  - The purpose was to identify risk factors for the two most common modes of death
      in chronic congestive heart failure (CHF) in 190 consecutive patients discharged
      with CHF. They were examined with clinical evaluation, blood chemistry, chest X
      ray, exercise testing, echocardiography, isotope ventriculography and Holter
      monitoring. Mortality after one year was 21%, after two years 32%. Of 60 deaths,
      33% were sudden and 49% due to pump failure. Multivariate analyses identified
      totally different risk factors for sudden death: ventricular tachycardia, S
      sodium < or = 137 mmol/l, S-magnesium < or = 0.80 mmol/l, S-creatinine > 121
      mumol/l, and maximal change in heart rate during exercise < or = 35/min. For
      death from progressive pump failure: New York Heart Association class 3 + 4,
      delta heart rate over 24 h < or = 50/min, low ejection fraction, high resting P
      noradrenaline, S-urea > 7.6 mmol/l, S-potassium < 3.5 mmol/l, and maximal
      exercise duration < or = 4 min.

PMID- 9922687
TI  - [Attitude of general practitioners to the importance of gender and diet in
      disease prevention].
AB  - Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a
      questionnaire on attitudes to include information on gender and diet in the
      strategy for prevention of coronary heart disease, cancer, osteoporosis, and
      overweight/underweight. Risk factors for disease in general were ranked as
      follows: smoking, alcohol, stress, diet, physical exercise, heredity and hygiene.
      The patients' lack of motivation, insufficient time for each patient, and
      inadequate knowledge about nutrition were stated as barriers to dietary
      counselling. The GPs stated that the gender of the patient was important only to
      the counselling on osteoporosis. Lack of time and insufficient knowledge were
      perceived as barriers for including gender specific issues in prevention. It is
      concluded that GPs consider dietary counselling important but lack time and
      knowledge. The results point at a need for better pre- and postgraduate training
      in nutrition, and for a better reimbursement system for time spent on prevention.

PMID- 9922688
TI  - [Prevention in general practice. Are female and male patients treated the same
      way? A questionnaire study].
AB  - Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a
      questionnaire on practices regarding prevention of coronary heart disease (CHD),
      cancer, osteoporosis, and overweight/underweight. Half of the GPs were questioned
      about the issue of prevention based upon female case stories and the other half
      on male case stories with identical wording. The GPs more often in relation to:
      Prevention of CHD gave dietary counselling and recommended weight loss to
      slightly overweight male than female patients. Prevention of cancers gave dietary
      counselling and recommended weight loss and increase of exercise to female than
      to male patients. Prevention of osteoporosis recommended a supplement of calcium
      and vitamin D to female than to male patients. Treatment of underweight
      recommended weight gain and discussion of psycho-social issues to underweight
      female than male patients. In conclusion, GPs distinguish between men and women
      in relation to prevention strategies in general practice. There is a need for
      well-described prevention and action strategies with relevant gender
      differentiation for use in general practice.

PMID- 9922690
TI  - [Serum inhibin B as a marker of spermatogenesis].

PMID- 9922689
TI  - [Transient arterial hypertension following an adder bite in a six six-year-old
      boy].
AB  - A case of arterial hypertension following an adder bite (Vipera Berus) in a six
      year-old boy is presented. Initially he had gross local symptoms and mild
      systemic symptoms, but was not treated with viper venom antiserum. Ten days after
      the initial admittance he developed symptoms of high blood pressure. Microscopic
      haematuria was found, and renal function was mildly impaired. It was concluded
      that the adder bite had caused the temporary rise in arterial blood pressure and
      renal dysfunction. Treatment with viper venom antiserum is recommended if local
      symptoms progress to involve the trunk or if systemic symptoms evolve.

PMID- 9922691
TI  - [Malaria prophylaxis one more time].

PMID- 9922692
TI  - [Confusion in the care of hearing disorders].

PMID- 9922694
TI  - [Virus inactivation of the donor plasma is not "Dagens Medicin"].

PMID- 9922693
TI  - [The National Board of Health Administration is basically wrong concerning DNA
      analysis].

PMID- 9922695
TI  - [Treatment of primary hyperparathyroidism].

PMID- 9922696
TI  - [Urinary tract diseases].

PMID- 9922697
TI  - [Renal and urinary tract abnormalities in small children].
AB  - The purpose of this study was to investigate frequency and pattern of urological
      abnormalities in children younger than two years of age in the county of
      Frederiksborg, Denmark, with a catchment area of about 350,000 people, and
      furthermore to investigate in which way the urological abnormalities were
      diagnosed. From 1994-1996 a total of 35 children younger than two years of age
      were found to have urological abnormalities. Fourteen patients had a
      ultrasonographical prenatally diagnosed urological abnormality, which was
      confirmed postnatally. Twenty-one children were diagnosed with urological
      abnormalities after presentry with their first urinary tract infection. The
      obstructive urological diagnoses: congenital hydronephrosis, congenital
      megaureter and posterior urethral valves made up to 57% (20/35) of the
      abnormalities. Nine boys were operated upon; three for unilateral hydronephrosis,
      two for posterior urethral valves, one for unilateral megaureter and three for
      phimosis. Two girls were treated with oestrogen for labial fusion. Urological
      abnormalities which were treated were found among the ultrasonographically
      diagnosed abnormalities, apart from phimosis and labial fusion. The frequency of
      urological abnormalities was 0.25% in children younger than two years of age in
      Frederiksborg county. In conclusion, in 1994-1996 the frequency and pattern of
      urological abnormalities in Frederiksborg county was in accordance with the
      figures in the literature. Urological abnormalities requiring treatment were
      diagnosed in 11 children; 55% (6/11) ultrasonographically and 45% (5/11) by
      examination of the external genitalia of children younger than two years of age
      at the time of the first diagnosed urinary tract infection.

PMID- 9922698
TI  - [To whom are roller-skaters harmful? A questionnaire among roller-skaters].
AB  - The number of roller-skaters in Denmark has increased visibly during recent
      years. We found a high incidence of serious injuries among patients (n = 112) who
      attended our emergency department from June 14th to October 14th 1996. One third
      of the patients were diagnosed with a fracture. Increasing numbers of the injured
      roller-skaters use protective gear, mostly wrist splints (37%). Wrist splints
      probably reduce the number of fractures, but do not completely eliminate the risk
      of fracture. It seems that roller-skaters are less harmful to other pedestrians
      than previously assumed.

PMID- 9922699
TI  - [General practitioners want continuing education. Audit registrations among 369
      physicians in Copenhagen].
AB  - The purpose of the study was to evaluate general practitioners' (GPs') interest
      in CME. A medical audit comprising 369 GPs in three counties was conducted in
      1996. During 28,550 consultations the participating GPs recorded clinical
      subject, handling of the consultation, problems in the consultation and perceived
      need for training in relation to the consultation. The interest in CME varied
      from GP to GP and from one clinical subject to another. Desire for CME was
      expressed in relation to 16% of the consultations, most frequently in relation to
      psychiatry, community medicine and musculoskeletal diseases. Theoretical courses
      were the learning style most often preferred, especially for subjects requiring
      biomedical knowledge. Newer educational methods were also listed. Organisers of
      CME for general practitioners should be aware of the wide range of needs and
      wishes for CME among general practitioners.

PMID- 9922700
TI  - [An outpatient unit for early pregnancy. Establishment and effects on the pattern
      of hospital admissions].
AB  - The aim of the study was to evaluate the effect of an assessment of complications
      in early pregnancy in an "early pregnancy unit" opened in May 1993. The purpose
      of the "early pregnancy unit" was to avoid routine admission of women with
      pain/bleeding in early pregnancy. All general practitioners were informed of the
      possibility of referring patients to examination and ultrasonography in the
      "early pregnancy unit" during daytime, instead of acute admission to the ward.
      Data was compiled from the hospital admission and the emergency unit register for
      the years 1992-1996. These showed that admissions for early pregnancy
      complications decreased from 714 (1992) to 315 (1996) accounting for 41% (1992)
      and 16% (1996) of total admissions to the department, and 23% (1992) and 10%
      (1996) of the numbers of deliveries, respectively. Women referred between 00:00
      hours and 7 a.m. accounted for 23% (1992) and 9% of admissions of total
      admissions or of deliveries (1996). It is concluded that initiation of the early
      pregnancy assessment unit resulted in a reduction in the number of admissions.
      The hospital staff experienced a reduced workload during the night.

PMID- 9922701
TI  - [T validity of the diagnosis of urinary tract infection in children under two
      years of age].
AB  - In the Department of Paediatrics at Hillerod a valid diagnosis of urinary tract
      infection in children is defined to be at least 10.000 bacteria/ml. in two
      midstream specimens of urine or any bacterial growth in urine collected by a
      suprapubic aspiration or by bladder catheterisation. We decided to study if these
      criteria were fulfilled in our department, which takes care of urinary tract
      infections in children in the county of Frederiksborg with a catchment area of
      about 350.000 people. From 1994-1996 a total of 60 children younger than two
      years of age were treated for their first suspected urinary tract infection. The
      diagnosis was valid in 37% of the cases. Eighty-eight percent of the children
      received parenteral antibiotics for at least three days, and 86% were discharged
      with prophylactic antibiotics. All underwent urological ultrasonographic
      examination and 70% underwent an isotope micturition cystourethrography. Among
      patients with a valid diagnosis 68% were boys and 50% had urological
      abnormalities, whereas among patients without a valid diagnosis there were 33%
      boys (p < 0.025) and 24% had urological abnormalities (p = 0.0734). A valid
      diagnosis of a first urinary tract infection was established in 0.15% of children
      younger than two years of age in the county of Frederiksborg. This is lower than
      previously reported. The problem of false positive urinary tract infections thus
      may be important in general.

PMID- 9922702
TI  - [Laparoscopic cholecystectomy at a university hospital department. Trends].

PMID- 9922703
TI  - [Demographic and epidemiologic indicators of health care costs. Elderly and
      mentally ill are the most expensive ones within the health care services].

PMID- 9922704
TI  - [Treatment of gallstones in Denmark].

PMID- 9922705
TI  - [Diphtheria--is the immunity satisfactory?].

PMID- 9922706
TI  - The use of essential drugs. Eighth report of the WHO Expert Committee (including
      the revised Model List of Essential Drugs).
AB  - This report presents the recommendations of a WHO Expert Committee responsible
      for updating and revising the Model List of Essential Drugs. The first part
      provides guidance for countries wishing to establish national programmes for
      essential drugs, and includes discussion of quality assurance, essential drugs
      for primary health care, post-registration drug studies, drug information and
      educational activities, and research and development. In the light of increasing
      resistance to antimicrobials, particular attention is drawn to the need for and
      use of reserve antimicrobials. The second part presents the tenth revised model
      list, together with details of changes that have been made, a glossary of terms
      and an alphabetical list of all the drugs included.

PMID- 9922707
TI  - [Desensitizing function of calcium mobilized by the postsynaptic neuronal-type
      nicotinic acetylcholine receptors at the neuromuscular junction].
AB  - Neuronal-type nicotinic acetylcholine receptors (N-nAChR) are co-localized with
      muscle-type (M-)nAChR in the postjunctional endplate membrane of adult skeletal
      muscle fibers. The postsynaptic desensitizing functions of the N-nAChR at the
      neuromuscular junction and at single skeletal muscle cells have been investigated
      using aequorin luminescence and fluorescence confocal imaging. A biphasic
      elevation of local intracellular Ca2+ is elicited by prolonged nicotinic action
      at the mouse muscle endplates. The contractile fast and non-contractile slow Ca2+
      components are operated by postsynaptic M- and colocalized N-type nAChR,
      respectively. We have named the latter slow one RAMIC (receptor-activity
      modulating intracellular Ca2+). The N-nAChR are activated by nicotine and
      choline, and RAMIC are antagonized by methyllycaconitine and dihydro-beta
      erythroidine. Neuromuscular functions may be regulated by a dual nAChR system to
      maintain the normal postsynaptic excitability. Certain N-nAChR may be also
      endowed with the same functional role in the central nervous system.

PMID- 9922709
TI  - [Chemistry of indoles: new reactivities of indole nucleus and its synthetic
      application].
AB  - This review summarizes our studies on the development of new reactivities of the
      indole nucleus and on its application for the synthesis. These studies involve
      the following five main subjects: 1) The Vilsmeier-Haack reaction was applied to
      1,2,3,4-tetrahydrocarbazole and its N-alkyl compounds. The conditions and the
      mechanisms of the formation of three kinds of products obtained from the latter
      compound were clarified, and among the three products, 1,9-dimethylcarbazole-3
      aldehyde was found to be useful for the syntheses of olivacine and ellipticine.
      2) The Fischer indole synthesis of various 2-substituted phenylhydrazones was
      examined in detail and it was found that the Fischer indole synthesis of 2
      sulfonyloxyphenylhydrazones served a new and convenient method for the synthesis
      of 7-oxygenated indoles. This reaction was applied to the synthesis of
      eudistomidin-A. 3) The reactivities of ethyl indole-2-carboxylate for acylation
      and bromination were also studied, and the use of this compound as a starting
      material for the synthesis of 4-methoxy-beta-carbolines was successfully
      investigated. 4) Acylation of ethyl pyrrole-2-carboxylate was concisely studied
      and this reaction was applied to the syntheses of benzene ring-substituted
      indoles and benz[f]indoles involving eupolauramine. 5) Two kinds of method for
      the debenzylation of N-benzylindoles were developed using either AlCl3-benzene or
      methyl lithium, and they are complementary with each other.

PMID- 9922708
TI  - [Cooperation of membrane proteins and cytosolic proteins in metabolic regulation-
      involvement of binding of hexokinase to mitochondria in regulation of glucose
      metabolism and association and complex formation between membrane proteins and
      cytosolic proteins in regulation of active oxygen production].
AB  - Changes in amount and activity of enzyme protein are critical factors in
      regulating intracellular metabolisms. However, since the metabolisms are
      proceeding in environment with complex architecture consisted of various
      membranes, spatial factors should be taken into consideration for the regulation.
      In this review, involvement of interaction between cytosolic and membrane
      proteins in metabolic regulation are discussed. It had been reported that
      hexokinase activity was found in mitochondrial fraction in spite of almost
      exclusive distribution of other glycolytic enzymes to soluble fraction, the
      tendency being marked in the brain and many types of tumor cells whereas
      mitochondrial hexokinase activity was quite low in the liver. Interested in such
      enzyme and tissue specificities, we investigated the significance and mechanism
      of the unique intracellular distribution of hexokinase. We found that
      mitochondria-bound hexokinase was more active than the cytosolic type in
      producing glucose 6-phosphate (G6P), probably due to the advantage in utilizing
      ATP produced in mitochondria. In addition, we also found that the binding
      stabilized hexokinase against G6P inhibition. As to the binding, it was reported
      that G6P released hexokinase from mitochondria while Mg2+ promoted the binding.
      In this respect, we found that polyamines promoted the binding at much lower
      concentration than that of Mg2+, and mitochondria-bound form had small
      hydrophobic domain at terminal region for the binding to porin on the outer
      membrane. Then, we found a protease which specifically cleaved the domain with
      little effect on catalytic activity and molecular size of the bindable form. Such
      a modifying protease was purified and identified as lysosomal cathepsin L. The
      protease activity was high in the liver and low in the brain, suggesting that the
      difference in the activity was responsible for the afore-mentioned tissue
      specificity. On the other hand, we examined regulatory mechanism for active
      oxygen production in neutrophils, since the production of superoxide anion (O2-)
      by NADPH oxidase was very low at the resting state while markedly increased on
      phagocytosis and chemical stimulation. Since the stimulants for the activation
      were so various in chemical nature, we postulated mechanism to converge the
      stimulation to the activation. Incidentally, we found increase in phosphorylation
      of 46-47 K protein, irrespective of the type of stimulation. Use of inhibitors
      and examination on the phosphorylation condition indicated protein kinase C (PKC)
      as the phosphorylating enzyme. In addition, we observed the 46-47 K protein
      existed in cytosol at resting state, while it was translocated to cell membranes
      in concurrence with the phosphorylation. Similar findings were obtained in many
      laboratories and those proteins were named cytosolic activating factors (and then
      p47-phox, etc.). These proteins associate with membrane proteins to constitutes
      the active from of NADPH oxidase. Next, we examined mechanism to shut off the O2-
      production, and found that the inactivation through disassembly of the
      constituents was attained by dephosphorylation of phosphorylated p47-phox by
      cytosolic protein phosphatase. Then we have also found that protein kinases other
      than PKC were involved in regulation of NADPH oxidase activity. Though
      phosphorylation of p47-phox etc. is deeply involved in the activation of NADPH
      oxidase, membrane perturbation, so-called priming, is required for the
      activation. We also reported some possible indications for the priming, and
      possible involvement of cytoskeletons in O2- production. Apart from protein
      phosphorylation, it has been reported that amphiphilic acidic compounds are
      potent activator for NADPH oxidase. We also have examined their effects to find
      that these compounds also caused the assembly of the NADPH oxidase constituents.
      Reversely, amphiphilic basic compounds suppressed suggesting significance of
      introduction of negative charge in NADPH oxidase activat

PMID- 9922710
TI  - [Establishment of microanalysis of prostaglandin metabolites by GC/MS and its
      clinical application].
AB  - We established microdetermination methods of prostaglandin (PG) metabolites by GC
      selected ion monitoring (GC-SIM) and applied them to the clinical investigations.
      At first the microdetermination of delta 17-6-keto-PGF1 alpha, a hydrolyzed
      metabolite of PGI2, is described. An authentic delta 17-6-keto-PGF1 alpha was
      prepared from eicosapentaenoic acid (EPA) incubated with a homogenate from the
      bovine aortic intima. [18O] delta 17-6-Keto-PGF1 alpha was synthesized to obtain
      an internal standard for GC-SIM of delta 17-6-keto-PGF1 alpha. A good linear
      response over the range of 10 pg-5 ng was demonstrated. Chromatographic
      conditions using a MP-65HT column presented nearly baseline separation of delta
      17-6-keto-PGF1 alpha and 6-keto-PGF1 alpha. Furthermore, a monoclonal antibody
      against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate
      delta 17-6-keto-PGF1 alpha in the human blood sera. Using the prepared
      immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly
      detected in the human blood sera by GC/MS analysis. We were able to detect delta
      17-6-keto-PGF1 alpha of the amount ranging from 6 to 26 pg/ml in the human blood
      plasma. The present method can be applied to the determination of delta 17-6-keto
      PGF1 alpha in the human urine and plasma. Diabetes mellitus induces platelet
      alterations such as hyperaggregation. Variations in PG production seem to be
      related to this phenomenon but the changes in PG levels remain unclear. So we
      microanalyzed the 11-dehydrothromboxane B2 (TXB2) and 2,3-dinor-6-keto-PGF1
      alpha, which were stable metabolites of TXA2 and PGI2, in the urine and
      investigated the relationship between the thromboxane/prostacyclin (TX/PGI) ratio
      and diabetes mellitus. The TX/PGI ratio in the urine of diabetics was higher than
      that of healthy volunteers. In murine, the TX/PGI ratio of STZ-induced mice was
      also higher than that of non-induced mice. The ratio of db/db mice also increased
      with the progress of diabetes mellitus. Furthermore, we investigated the
      relationship between the retinal vein occlusion (RVO), a thrombotic disease in
      which the retinal vein is blocked by blood aggregations, and the TX/PGI ratio.
      The TX/PGI level in patients with the RVO, who were not combine diabetes, was
      significantly higher than that in healthy volunteers. One of the causes of the
      RVO may be due to the variation of thromboxane production. This GC-SIM method can
      be used to determine the TX/PGI ratio in the urine.

PMID- 9922711
TI  - [Bioactive saponins and glycosides. XIII. Horse chestnut. (3): Quantitative
      analysis of escins Ia, Ib, IIa, and IIb by means of high performance liquid
      chromatography].
AB  - As a part of our studies on the characterization of bioactive saponin
      constituents of horse chestnut trees, a quantitative method using high
      performance liquid chromatography (HPLC) has been developed for four principle
      saponin constituents, such as escins Ia, Ib, IIa, and IIb, isolated from the
      seeds of European horse chestnut trees (Aesculus hippocastanum L.,
      Hippocastanaceae). As an application of this HPLC method, we examined the
      contents and compositions of these escins in the seeds of Japanese horse chestnut
      trees (A. turbinata BLUME) and in several commercial materials named as "beta
      escin". Additionally, the distribution of escins in the Japanese horse chestnut
      trees was examined, and escins were found to be contained only in the seeds.

PMID- 9922712
TI  - [Determination of sennoside A and sennoside B in formulation using capillary
      electrophoresis].
AB  - The determination of sennoside A (SA) and sennoside B (SB) by capillary zone
      electrophoresis was developed. The separation of SA and SB was performed in 100
      mM of the 3-[cyclohexylamino]-1-propanesulfonic acid (CAPS) buffer (pH 10.0), and
      the migration time of SA and SB was found to be both less than 7 min. This method
      was applied to the analyses of seven commercial formulations containing SA and SB
      without previous treatment. The statistical comparison of the results obtained
      from both capillary electrophoresis and HPLC methods revealed an absolute
      correlation.

PMID- 9922713
TI  - [Antioxidative effects of fluvastatin, and its major metabolites].
AB  - Fluvastatin (FV) is a highly potent inhibitor of 3-hydroxy-3-methylglutaryl-CoA
      (HMG-CoA) reductase. Recently, its antioxidant effect caused by inhibiting the
      formation of low density lipoproteins (LDL) in vitro has been reported. In this
      study, we reported the antioxidant effects of FV and its major metabolites in
      human (M-2, M-3, M-4, M-5, and M-7) on lipid peroxidation using rat liver
      microsomes. The extent of NADPH-induced microsomal (Ms) lipid peroxidation was
      determined by the thiobarbituric acid (TBA) assay. The antioxidant effect of each
      compound was shown as the percentage of inhibition on the formation of TBA
      reactive substances (TBARS) against the vehicle control. Probucol (PR), a potent
      antioxidant drug, was used as a reference control. The concentration of each
      compound in this experiment was set at 0.1 mM (final conc.). FV inhibited the
      formation of TBARS by 30 to 60% without depending on the used Ms concentrations
      (0.025-0.2 mg protein/ml). The antioxidant effects of M-2, M-3, and M-5 were
      comparable to that of FV at low Ms concentrations. At the highest Ms
      concentration, however, the antioxidant effects of these metabolites were
      considerably higher than that of FV. Inhibition of the formation of TBARS by M-4
      or M-7 was approximately 30% of the control and independent of the used Ms
      concentrations. The antioxidant effect of PR was comparable to those of M-2, M-3,
      and M-5 in this study. Pravastatin (PV), a potent inhibitor of HMG-CoA reductase,
      reduced the formation of TBARS around 20% at 0.25 or 0.5 mg protein/ml of Ms
      concentrations. But the value of percentage of inhibition was around 5% at 0.1 or
      0.2 mg protein/ml of Ms concentrations. In conclusion, the antioxidant effects of
      FV, M-2, M-3, and M-5 were found to be comparable to that of PR.

PMID- 9922714
TI  - Morphometric analysis of pancreatic carcinoma by computer-assisted image
      analysis.
AB  - This report describes the results of applying the interactive image analysis
      system for the measurement of some cytological parameters corresponding to
      features of adenocarcinoma of the pancreas. The present experiments were carried
      out by means of the digital cell image analysis of haematoxilyn and eosin stained
      archival standard glass slides of cancer bearing and healthy patients. Four
      different parameters describing the morphology of nuclei and nucleoli were
      selected to quantitate the differences between control and malignant tissues:
      area, perimeter, elongation, and extension. The parameters that showed the
      greatest differences between cancerous and normal pancreas were: area and
      elongation in the case of nuclei as well as area and perimeter for nucleoli.
      However, the results of this study suggest that none of the four analysed
      parameters can be selected alone to discriminate neoplastic from normal cells,
      but could be used all together in diagnosis of pancreatic cancer.

PMID- 9922715
TI  - Effect of tenotomy on extensor digitorum longus muscle in Sprague Dawley rats.
AB  - The effect of tenotomy on Extensor Digitorum Longus (EDL) muscle, brought about
      by removal of anterior tibialis muscle was studied in the rat. Hypertrophy as
      well as hyperplasia of the muscle fibres were observed following tenotomy of
      intact muscle. The transplanted muscle regenerated after tenotomy in the form of
      a flat strap. The weight, length, breadth and total muscle area of intact muscle
      increased but decreased in transplanted muscle following tenotomy. The number of
      muscle fibres/microscopic field increased during the entire experiment in intact
      muscle after tenotomy, while in transplant the number of fibres first decreased
      and then increased. The diameter of intact and transplanted muscle increased
      after tenotomy. The number and diameter of nuclei was normalized at the end of
      experiment in both groups. The DNA and RNA content was increased in intact muscle
      after tenotomy. In transplant DNA and RNA content first increased but than
      decreased. The protein content was increased in intact muscle at the end of the
      experiment but decreased in transplant after tenotomy.

PMID- 9922716
TI  - MRI temporal lobe volume measures and neuropsychologic function in Alzheimer's
      disease.
AB  - The authors performed quantitation of the temporal lobes using magnetic resonance
      imaging in 20 patients with mild-to-moderate Alzheimer's disease, 20 age-matched
      aged control subjects, and 26 healthy young volunteers. Compared to young
      subjects, aged controls showed volume reductions in amygdala (17%, p = 0.02),
      hippocampus (15%, p = 0.0001) and temporal lobe (22%, p = 0.0001). Compared to
      aged controls, Alzheimer's subjects showed further volume reductions in amygdala
      (33%, p = 0.0001) and hippocampus (20%, p = 0.006) but not temporal lobe (7%, p =
      0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly
      with the Mini Mental State (MMSE) score (adjusted r2 = 0.46, p = 0.0006) whereas
      right amygdala volume correlated inversely with the noncognitive ADAS score
      (adjusted r2 = 0.46, p = 0.0006). The authors conclude that significant volume
      changes occur in the temporal lobe in aging and in Alzheimer's disease, with the
      greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal
      neocortical atrophy and temporal limbic atrophy might be associated with
      different patterns of performance and behavior in Alzheimer's patients.

PMID- 9922717
TI  - A new dynamic method for detection of internal jugular valve incompetence using
      air contrast ultrasonography.
AB  - The internal jugular (IJ) valve is the only valve between the heart and the
      brain, preventing venous reflux into the IJ vein. Internal jugular valve
      competence has been tested by IJ venography. Doppler ultrasonography of the IJ
      vein and M-mode ultrasonography of the IJ valve, and color flow imaging (CFI) of
      the IJ vein. However, interpretation of venous Doppler and CFI is difficult, and
      venography is invasive. The purpose of this study was to evaluate the feasibility
      of a new dynamic method to test IJ valve competency, and to review the literature
      regarding the potential clinical importance of this pathophysiology. Ten patients
      had intravenous injection of agitated air and saline during Valsalva maneuver
      with B-mode monitoring and CFI of the right IJ vein. Contrast bubbles were
      clearly identified refluxing into the right IJ vein in 50% of patients. Air
      contrast studies more often showed IJ valve incompetence than CFI. Bubbles
      appeared in the IJ vein within 19.2 sec and persisted up to 282 sec. Bubble
      aggregation was also observed. There was no correlation between positive bubbles
      and the presence of spontaneous echo contrast on baseline B-mode imaging. Air
      contrast ultrasound venography (ACUV) is a new noninvasive method to assess
      competency of the IJ valves. This technique is feasible, appears to be more
      sensitive than CFI, and adds a new dimension to the study of the venous system in
      cerebrovascular disease. Potential clinical application includes evaluation of
      patients with increased central venous pressure, those with morning headaches,
      and those on positive end-expiratory pressure ventilators.

PMID- 9922718
TI  - Diagnostic yield of a 1-MHz transducer in evaluation of the basal cerebral
      arteries.
AB  - The authors examined the efficacy of a 1-MHz transducer in routine ultrasound
      monitoring. Fifty outpatients (34 women, 16 men; mean age, 65 +/- 2) with
      inadequate temporal bone window for examination with 2-MHz transducers were re
      examined with a 1-MHz transducer. Additionally, 50 controls (34 men, 16 women;
      mean age 49 +/- 2) with adequate temporal bone window were examined with both the
      1- and 2-MHz transducers. Signal quality was classified as good (GQ), adequate
      (AQ), or poor (PQ). Finally, 30 normal controls were examined with both
      transducers under standardized conditions, to evaluate potential differences in
      velocity measurements. A total of 90 temporal windows were lacking in the 50
      patients. Use of the 1-MHz transducer resulted in identification of the middle
      cerebral artery in 68 cases (76%; PQ, n = 13; AQ, n = 29; GQ, n = 26), the
      anterior cerebral artery in 51 cases (57%; PQ, n = 23; AQ, n = 17; GQ, n = 11)
      and the posterior cerebral artery in 46 cases (51%; PQ, n = 12; AQ, n = 21; GQ, n
      = 13). Examination was feasible with both transducers in the 50 controls, with
      minimal differences in signal quality between the two transducers. Correlation
      between velocity values acquired with the 1- and 2-MHz transducers was
      significant for all vessels examined. Best values were measured for the middle
      cerebral artery, followed by the anterior cerebral artery and posterior cerebral
      artery. The authors conclude that the use of the 1-MHz transducer increases the
      yield of transcranial Doppler sonography.

PMID- 9922719
TI  - Intima-media thickness of carotid arteries in borderline hypertensives.
AB  - The purpose of this study was to assess the effect of the main risk factors for
      cardiovascular disease on the process of subclinical atherosclerosis in
      originally borderline hypertensives. The relation of far wall common carotid
      artery intima-media thickness (IMT CCA) measured by B-mode ultrasound to smoking,
      body mass index (BMI), blood pressure, lipids, and angiotensin-converting enzyme
      (ACE) gene polymorphism was analyzed. In 48 subjects examined (mean age, 61.9 +/-
      2.54 years), median IMT CCA was 0.708 mm. Statistically significant differences
      in BMI (26.5 vs. 29.2 kg/m2, p < 0.025) and HDL-cholesterol level (1.42 vs. 1.1
      mmol/l, p < 0.025) between the first and third tertile of IMT CCA were found. No
      differences were observed between "controls" and "cases" in blood pressure, total
      cholesterol, and triacylglycerols. No significant differences in IMT CCA were
      found between smokers and nonsmokers and among different alleles of the ACE gene.
      These data reflect the importance of HDL-cholesterol and BMI on the process of
      atherosclerosis within an otherwise homogeneous group of patients.

PMID- 9922720
TI  - Cerebral blood flow velocity during occlusive manipulation of patent ductus
      arteriosus in children.
AB  - Patent ductus arteriosus (PDA) with left-to-right shunting modifies the Doppler
      flow pattern of the intracranial circulation. The ability of increases in
      cerebral blood flow velocity (CBFV) to predict shunt resolution during PDA
      occlusion was evaluated. A 2 MHz transcranial Doppler (TCD) monitored diastolic
      and mean CBFV, plus the systolic/mean CBFV ratio in the middle cerebral artery
      from before (baseline) to immediately after PDA occlusion. Shunt resolution was
      verified by echocardiography and/or angiography. A minimum of 40% increase in
      diastolic-CBFV from baseline was considered successful resolution. Patients were
      age-stratified into group I (< 15 months; n = 23) and group II (> 15 months; n =
      10). Thirty-three children were studied (age, 0.1 to 109 months) during surgical
      (n = 22) or coil occlusions (n = 11). Transcranial Doppler successfully
      identified shunt resolution in 78% of cases in group I, as compared to 0% in
      group II (p < 0.01). Identification rate decreased from 79% in cases of minimum
      ductal diameter of 3 mm (n = 19) to 21% in smaller ductuses (n = 14) (p < 0.01).
      Body weight and left-atrium size (p = 0.004) in group I and PDA diameter in group
      II (p = 0.02), were the only preoperative ductal parameters associated with
      diastolic-CBFV changes after ductus occlusion. Transcranial Doppler detects shunt
      resolution in infants with moderate to large PDAs.

PMID- 9922721
TI  - Crossed cerebellar diaschisis: the role of motor and premotor areas in functional
      connections.
AB  - The authors assessed the relationship between crossed cerebellar diaschisis (CCD)
      and cortico-pontine cerebellar pathway (CPCP) damage in 29 chronic supratentorial
      infarct patients to elucidate the role of motor and premotor areas for functional
      cerebro-cerebellar connections. The CCD rate was calculated from side-to-side
      cerebellar count differences on 123I-IMP single-photon emission computerized
      tomography images. Neuronal damage was estimated by the three scores of computed
      tomography density from equal to normal brain tissue (score 0) to equal to
      cerebrospinal fluid (score 2) in the 4 major regions on CPCP; frontal
      association, motor and premotor, sensory and parietal associations, and the
      posterior limb of the internal capsule. Two-factor factorial ANOVA by the score
      and the region revealed significant differences of the CCD rate in the score
      factor (score 0 or 1 vs. score 2, p = < 0.05) and the independency of these two
      factors. Categories determined by the scores in each region were analyzed by
      multiple stepwise regression analysis using the theory of quantification I, in
      which significant correlation only between CCD and the necrotic density (score 2)
      in motor and premotor areas were demonstrated (r = 0.515, p = < 0.05). The
      authors conclude that neuronal loss in motor and premotor areas seem to
      contribute significantly to functional cerebro-cerebellar disconnections.

PMID- 9922722
TI  - Transcranial Doppler sonography guided by magnetic resonance angiography for
      improved monitoring of intracranial arteries.
AB  - Transcranial Doppler (TCD) sonography combines the advantages of real-time
      hemodynamic information, cost-effectiveness, and bedside application. However,
      measurements can be difficult to reproduce because the spatial resolution and the
      determination of insonation angles are limited. The purpose of this study was to
      use the high anatomic resolution of three-dimensional (3D) magnetic resonance
      angiography (MRA) images for the stereotactic guidance of TCD in order to improve
      the accuracy and reproducibility of TCD examinations. The MRA examinations were
      performed on a 1.5 T scanner using a 3D flow compensated gradient-echo sequence.
      A noninvasive stereotactic mask was used for image registration. The MRA data
      were then transferred to a personal computer. An infrared tracking system
      registered the position of the head and the ultrasound probe during TCD. This
      enabled the authors to superimpose a virtual ultrasound beam onto the MRA
      projections of the intracranial arteries displayed on the monitor of the personal
      computer. This allows the examiner to easily identify the insonated intracranial
      artery and displays the insonation angle. In volunteer examinations (n = 10), the
      accuracy and reproducibility for the localization of specific vessel segments was
      2.48 mm for the middle cerebral artery and 2.81 mm for all insonated intracranial
      arteries (middle cerebral artery, anterior cerebral artery, internal carotid
      artery, and posterior cerebral artery). Without navigation the reproducibility of
      vessel segment insonation dropped to 4.7 mm for the middle cerebral artery and to
      4.84 mm for all vessels. The authors conclude that 3D MRA, acquired as an initial
      procedure in patients with intracranial vascular disorders, can be used to
      provide stereotactic guidance for repeated TCD examinations. This facilitates the
      reproducible insonation of specific vessel segments.

PMID- 9922723
TI  - Orthostatic-mediated hypoperfusion in limb-shaking transient ischemic attack.
AB  - In patients with severe carotid stenosis or total occlusion, episodic
      contralateral motor dysfunction is more likely related to cerebral hypoperfusion
      than epileptogenic activity. A man with orthostatic-mediated right-sided limb
      shaking was found to have total left internal carotid artery occlusion. There was
      prominent reduction of cerebrovascular reserve seen on single photon emission
      computed tomography (SPECT) performed with and without acetazolomide. During
      assumption of an upright position transcranial Doppler (TCD) revealed a marked
      attenuation of the left middle cerebral artery flow pattern not associated with
      changes during electroencephalographic monitoring, even after administration of
      acetazolomide. In this man, limb shaking episodes were attributed to
      hypoperfusion of the contralateral cerebral hemisphere, and not to epileptogenic
      activity.

PMID- 9922724
TI  - Clinical application of magnetoencephalography in a patient with corticobasal
      degeneration.
AB  - Previous neuroimaging studies in corticobasal degeneration (CBD), such as MRI and
      positron emission tomography, showed lateralized cortical atrophy and a decrease
      in cortical oxygen metabolism, respectively. The advantage of
      magnetoencephalography in the research of the auditory system is that activity of
      both hemispheres can be detected separately. Auditory-evoked magnetic fields
      (AEFs) were then applied to a patient with corticobasal degeneration. The
      strength of N100m equivalent current dipoles (ECD) in left hemisphere was
      extremely smaller (20 nAm) than that in right hemisphere (48 nAm). This results
      implies that CBD patient might have a decrease in the number of neurons in the
      primary auditory cortex. This study suggests that AEF measurement is one of the
      most powerful tools for detecting latent impairment of auditory function in
      patients with corticobasal degeneration.

PMID- 9922726
TI  - The economic well-being of elderly people and children in a changing society
AB  - As the United States meets its obligation to provide social security benefits for
      a growing population of elderly people and as the U.S. economy increasingly is
      exposed to global competition, social policy for the elderly population cannot-
      and should not--be developed or assessed in isolation: It should be assessed in
      the context of changing society. This article discusses the growing imbalance in
      the economic conditions of elderly people and children. It argues that this
      growing imbalance should be considered a threat for the social and economic
      development of the United States. It encourages the leaders of the elderly
      population to get involved in the drive to channel more resources to children.

PMID- 9922725
TI  - Neuroimaging findings in a patient recovering from global alexia to spelling
      dyslexia.
AB  - The authors report findings in a 67-year-old right-handed man who had an ischemic
      infarct in the territory of the left posterior cerebral artery. The clinical
      manifestation consisted mainly of total alexia without agraphia. The patient
      gradually recovered, subsequently showing the syndrome of spelling dyslexia.
      Cerebral MR-images revealed a circumscript infarction of medial and basal parts
      of left temporal lobe. In the acute stage [99mTc]HM-PAO SPECT was characterized
      by a diminished uptake in the definitely infarcted area and hyperfixation in the
      region of the left forceps major. Because high retention of HM-PAO indicates
      potentially salvageable tissue after an ischemic event, the depicted area might
      be correlated with the recovery of function. Thus, the authors' neuroimaging data
      give further support to the assumption that the left forceps major is a critical
      area for global alexia, whereas spelling dyslexia is due to involvement of the
      left medio-basal temporal lobe.

PMID- 9922727
TI  - Custodial grandparents in Latino families: patterns of service use and predictors
      of unmet needs
AB  - This article examines patterns of service use and predictors of unmet needs among
      a purposive sample of 74 Latino grandparent caregivers in New York City. Study
      participants tended to be unmarried, middle-aged, and older women who were
      monolingual Spanish speaking and had very low levels of educational attainment
      and income. Nearly all respondents were connected to the formal service system,
      yet they still reported substantial unmet needs. Lack of knowledge was the major
      barrier to service use, and predictors of unmet needs included low education,
      poor health, high levels of life stress, and lack of reliable help with child
      rearing. Implications for policy and practice strategies that focus on role
      related needs of Latino custodial grandparents are discussed.

PMID- 9922728
TI  - Living with HIV/AIDS: the voices of HIV-positive mothers
AB  - The study reported here was undertaken to investigate the experiences of HIV
      positive mothers with the system of services designed to help them, how they cope
      with the infection, particularly as it relates to parenting, and their concerns,
      preferences and plans for the future care of their children. A focus group method
      was selected because it is well suited for this type of exploratory research. A
      total of 40 HIV-positive mothers participated in six different focus groups. The
      issues that emerged from the data analysis revealed that, using systems theory,
      they could be logically classified by the type or level of system in which the
      issue was primarily located. The three system levels were (1) individual and
      family, (2) organizations and providers, (3) policy and community. Within each of
      these categories, issues could be further delineated by whether they provided
      women with resources or presented them with additional stress. Conclusions and
      recommendations for providers are made based on the systems framework that gave
      structure to the results.

PMID- 9922729
TI  - HIV-related stigma in a sample of HIV-affected older female African American
      caregivers
AB  - Older women of color increasingly act as informal caregivers for adults and
      children with HIV disease. Nineteen older female (mostly African American)
      informal caregivers of HIV-infected individuals participated in qualitative
      interviews to explore their experiences with HIV-related stigma. Perceived and
      directly experienced stigma were examined in the context of disclosure of the
      presence of HIV disease. Overt HIV-related stigma was rarely experienced by these
      respondents, primarily because they had not widely disclosed the presence of HIV
      in the family and therefore had not given anyone the opportunity to ostracize or
      judge them. HIV-related stigma was internalized, so that disclosure decisions
      were based on their anticipation of censure. There also was evidence of
      associative stigma and of stigma management. The findings suggest the need for
      social work practitioners to increase awareness of the needs of stigmatized,
      isolated HIV-affected caregivers. Practitioners should conduct aggressive
      outreach and strive to provide more support to this often invisible population of
      caregivers to HIV-infected people.

PMID- 9922730
TI  - Symposium: Towards Optimized Treatment Outcomes for Dental Implants. Toronto,
      Ontario, April 24-25, 1998. Proceedings.

PMID- 9922731
TI  - Mechanisms of endosseous integration.
AB  - Although the clinical term "osseointegration" describes the anchorage of
      endosseous implants to withstand functional loading, it provides no insight into
      the mechanisms of bony healing around such implants. Nevertheless, an
      understanding of the sequence of bone healing events around endosseous implants
      is believed to be critical in developing biologic design criteria for implant
      surfaces. RESULTS AND DISCUSSION: This discussion paper shows that peri-implant
      bone healing, which results in contact osteogenesis (bone growth on the implant
      surface), can be phenomenologically subdivided into three distinct phases that
      can be addressed experimentally. The first, osteoconduction, relies on the
      migration of differentiating osteogenic cells to the implant surface, through a
      temporary connective tissue scaffold. Anchorage of this scaffold to the implant
      surface is a function of implant surface design. The second, de novo bone
      formation, results in a mineralized interfacial matrix, equivalent to that seen
      in cement lines in natural bone tissue, being laid down on the implant surface.
      Implant surface topography will determine if the interfacial bone formed is
      bonded to the implant. A third tissue response, that of bone remodeling, will
      also, at discrete sites, create a bone-implant interface comprising de novo bone
      formation. CONCLUSION: Treatment outcomes in dental implantology will be
      critically dependent on implant surface designs that optimize the biologic
      response during each of these three distinct integration mechanisms.

PMID- 9922732
TI  - The choice of alloplastic materials for oral implants: does it really matter?
AB  - PURPOSE: To provide a review of the overall nature and properties of materials
      used for manufacturing of endosseous dental implants. RESULTS AND DISCUSSION: The
      importance of chemical qualities of implant surfaces is highlighted; special
      reference is given to titanium and its oxides. The process of bioadhesion is
      described, and comments are made on its relation to a range of given
      biomechanical factors. CONCLUSION: In the author's opinion, based on the
      arguments presented, the material properties of alloplastic implant materials
      have a strong influence on implant retention and stability, and thus on an
      implant's capacity to achieve so-called osseointegration.

PMID- 9922733
TI  - Surgical determinants of clinical success of osseointegrated oral implants: a
      review of the literature.
AB  - PURPOSE: This article reviews the current knowledge about the influence of
      surgical factors on implant failure in routine cases and in those where implants
      have been used in conjunction with bone augmentation procedures. MATERIALS AND
      METHODS: Clinical reports published in major scientific journals served as the
      basis for this review. RESULTS: With few exceptions, most clinical reports were
      on screw-shaped titanium implants. High failure rates are associated with poor
      bone quality and the use of short implants in the athrophic maxilla, irradiation,
      and bone-grafting procedures of the athrophic maxilla. Evidence for high long
      term failure rates of press-fit cylinders was found. Moreover, limited clinical
      experience, lack of preoperative antibiotics, and smoking may lead to higher
      failure rates. CONCLUSION: There is a need for further research to increase the
      success rates in the severely resorbed maxilla. Because of a lack of proper
      documentation with respect to the great majority of currently used oral implant
      designs, the influence of different factors and their long-term results remain
      unknown.

PMID- 9922734
TI  - The implant-mucosal interface and its role in the long-term success of endosseous
      oral implants: a review of the literature.
AB  - PURPOSE: This article reviews the literature on the anatomy and the role of the
      implant-mucosal interface in the long-term success of oral endosseous implants.
      MATERIALS AND METHODS: In vitro, in vivo animal, and in vivo human studies are
      reviewed and discussed. RESULTS: The anatomy of the implant-mucosal interface is
      described. The interface shares many features with periodontal mucosa. A
      clinically healthy implant-mucosal interface is a routine and predictable
      occurrence. The validity of using traditional clinical periodontal parameters to
      indicate or predict changes in peri-implant marginal bone height is unproven,
      especially if inflamed mucosal tissues are present. CONCLUSION: In general, the
      human host response of peri-implant mucosa to long-term functional challenges is
      favorable.

PMID- 9922735
TI  - Microbial colonization of the peri-implant environment and its relevance to long
      term success of osseointegrated implants.
AB  - PURPOSE: This article provides a critical examination of the literature on the
      colonization of the peri-implant environment and its impact on clinically
      significant infection, in the context of a comparison with the microbial etiology
      of periodontitis. MATERIALS AND METHODS: Previous journal article bibliographies
      and MEDLINE searches provided comprehensive access to current literature on this
      topic. References that provided significant or novel advancements in knowledge
      were included in this review. Since it was prepared for a workshop that would
      examine this issue critically, this review offers provocative commentary.
      RESULTS: There are many similarities in peri-implant and periodontal
      microbiology, both in health and in infection leading to progressive
      deterioration. Periodontal pockets serve as reservoirs for the colonization of
      implants by periodontal pathogens in partially edentulous patients. Implant
      design and material composition affect the colonization of implant surfaces.
      Infections around implants can be treated by similar strategies used for
      periodontitis. Investigators are beginning to adopt research designs used in
      periodontology to study the pathogenesis and treatment of peri-implant
      infections. Research in this area is impeded by the lack of surrogate variables
      for crestal bone resorption. CONCLUSION: Some implants fail as a result of
      infection, but the frequency of failure by infection or any other cause is
      unknown. This paper suggests areas where much more additional research is needed,
      including critical consideration of strategies that have led to the past few
      decades' advancements in the pathogenesis of periodontitis.

PMID- 9922736
TI  - Imaging techniques and image interpretation for dental implant treatment.
AB  - PURPOSE: This article reviews the literature on radiographic imaging techniques
      and image interpretation for dental implant treatment. MATERIALS AND METHODS:
      MEDLINE was used to identify published peer-reviewed literature for this report.
      RESULTS: Radiographic images are indispensable in the evaluation of osseous
      structures when planning treatment for dental implants. Potential bone sites for
      implant placement can be assessed clinically by means of palpation or probing
      through the mucosa; however, diagnostic imaging provides the best means for
      indirectly measuring bone dimensions. After healing of the implant site, the
      application of radiology is useful to verify the amount of bone adjacent to the
      implant and that the transmucosal abutments fit the implant. Upon completion of
      the implant prosthesis, radiology may be used to monitor initial and long-term
      success of implant treatment. CONCLUSION: Recommendations for the application of
      radiology over the course of treatment are made for various implant cases ranging
      from the overdenture to the single-tooth implant.

PMID- 9922737
TI  - Patient-based assessment of the outcomes of implant therapy: a review of the
      literature.
AB  - PURPOSE: This paper reviews the literature on patient-based assessments of
      implant therapy. MATERIALS AND METHODS: A search of the literature produced 22
      papers describing 19 studies. RESULTS: Only 3 of the 19 studies were randomized
      controlled trials. Consequently, most have design flaws that threaten their
      internal validity. In addition, the measurement of patient-based outcomes was
      generally poor, further weakening the evidence provided by the research conducted
      to date. The randomized trials indicate that implants improve chewing ability and
      satisfaction with dentures but have not demonstrated effects with respect to the
      quality of life. CONCLUSION: Further research is needed using randomized
      controlled trial designs. Outcome measures need to be more carefully selected so
      as to reflect patients' concerns.

PMID- 9922738
TI  - Sensory disturbances associated with implant surgery.
AB  - PURPOSE: This paper presents a critical review of the literature on neurosensory
      disturbances associated with implant surgery. MATERIALS AND METHODS: The reviewed
      literature includes mainly retrospective implant studies and patients' surveys,
      as well as a few prospective psychophysical studies on sensory disorders
      following maxillofacial surgeries. RESULTS: The available data suggest that
      injury to the peripheral branches of the trigeminal nerve and subsequent sensory
      disturbances are potential complications following implant surgery. Cross
      sectional studies suggest that gross tactile sensation was regained in the vast
      majority of patients. However, data on the spatial and temporal patterns of
      recovery of this and other somatic sensation such as fine touch, nociception, and
      temperature sense after implant surgery is still lacking. The prevalence of
      sensory disturbances depends on several factors: the site of implant placement,
      the type of surgical procedures adopted, the design of the studies, the
      sensitivity of the testing methods, the choice of the outcome measures, and the
      terminology used to describe sensory disturbances. Extreme variation in the
      reported prevalence of neurosensory disturbances (0% to 100%) suggest that these
      problems have not been adequately evaluated. CONCLUSION: Although sensory
      disturbances are transient in the majority of implant patients, their profound
      impact on the quality of life of the subjects affected and the possibility that
      they may persist clearly indicate that they should be identified and evaluated
      through prospective studies, using validated testing protocols and outcome
      measures.

PMID- 9922740
TI  - Assessment of implant stability as a prognostic determinant.
AB  - PURPOSE: This paper aims to establish the parameters necessary to monitor
      successful implant placement and osseointegration. RESULTS AND DISCUSSION:
      Implant stability is considered to play a major role in the success of
      osseointegration. Primary implant stability at placement is a mechanical
      phenomenon that is related to the local bone quality and quantity, the type of
      implant and placement technique used. Secondary implant stability is the increase
      in stability attributable to bone formation and remodeling at the implant/tissue
      interface and in the surrounding bone. Techniques for measuring implant stability
      and osseointegration, including the clinical measurement of cutting resistance
      during implant placement and removal torque following osseointegration, are
      discussed. Nondestructive test methods, including impact-based techniques such as
      the Periotest and the Dental Fine Tester, are also discussed. An alternative
      method, resonance frequency analysis, is described in detail. CONCLUSION: It is
      clear that stability both at placement and during function is an important
      criterion for the success of dental implants. Quantitative methods, including
      resonance frequency analysis, can yield valuable information.

PMID- 9922739
TI  - The effects of age, jaw site, and bone condition on oral implant outcomes.
AB  - PURPOSE: This paper reviews literature on age and jaw site in relation to jawbone
      quantity and quality and the osseointegration of endosseous oral implants.
      RESULTS AND DISCUSSION: The condition of jawbone is both age- and site-specific.
      However, increased age does not appear to affect the clinical potential for
      osseointegration or the rate of crestal bone resorption observed around oral
      implants. In contrast, jaw site is related significantly to osseointegration
      potential; mandibular sites tend to be more successful than maxillary sites. The
      reason for this may be that jawbone quality and quantity are often more
      compromised in maxillary than in mandibular sites. However, evaluation of this
      relationship has been hampered by a lack of evidence to support the validity and
      reliability of methods used to assess jawbone condition preoperatively.
      Furthermore, short-term evidence suggests that high rates of implant success can
      be achieved in maxillary sites, even those with low trabecular density, if an
      adequate volume of bone exists to accommodate the implants. Although the rate of
      crestal bone resorption around oral implants is usually low and may not be site
      specific, there is some evidence that it may be greater in sites with less
      preoperative resorption associated with shorter periods of edentulism. This
      pattern of bone loss could jeopardize long-term implant outcomes especially in
      younger implant patients. Another concern in young growing patients is that their
      prosthetic outcome may become compromised because osseointegrated implants cannot
      keep pace with growth and development in surrounding structures. CONCLUSION: To
      improve our understanding of how the age- and site-specificity of jawbone
      condition affects oral implant outcomes, research needs to be aimed at
      establishing reliable and valid measures of preoperative jawbone condition, and
      at better documenting the effects of jawbone condition on oral implant outcomes.

PMID- 9922741
TI  - Successful long-term treatment outcomes in the field of osseointegrated implants:
      prosthodontic determinants.
AB  - PURPOSE: Because existing implant success criteria have not met with widespread
      use, consensus is needed among professionals working in the field as to what
      constitutes implant success. This article discusses implant success within the
      context of prosthesis success, and argues that successful use of implants cannot
      be judged without prosthesis consideration. RESULTS AND DISCUSSION: A framework
      for evaluating clinical success of prosthodontic treatment is presented. A
      context for judging success by presenting related topics that include contrasting
      process and outcome measures, and consideration of long-term outcomes that have a
      tangible meaning to the patient (i.e., are patient-based), is argued for. A
      hierarchy of outcomes is proposed for a better understanding of the relative
      strengths associated with various outcomes. Emphasis is given to the concept of
      prosthodontic treatment being prescribed to reduce the patient-specific burden
      associated with the missing tooth condition. CONCLUSION: The challenge is to
      define the best applications of dental implants within the broad context of
      prosthodontic options through demonstrated advantages over more conventional
      options. A broad understanding of "success" from multiple outcome domains is most
      likely to give the truest measure for implant application within the context of
      possible prosthodontic options for all patients.

PMID- 9922742
TI  - Development and manufacture of prosthodontic components: do we need changes?
AB  - PURPOSE: Prosthodontic components for implant treatment have been developed with
      minimal reported scientific investigation. This paper aims to highlight a number
      of problems caused by this approach to the development and marketing of
      prosthodontic components and to suggest solutions. CONCLUSION: Prosthodontic
      components must be developed with a scientific approach that involves both
      laboratory and clinical testing so as to optimize treatment outcomes in the
      future.

PMID- 9922743
TI  - Determinants of correct clinical reporting.

PMID- 9922744
TI  - Histopathological study of the use of freeze-dried allogenic dentin powder and
      True Bone Ceramic as apical barrier materials.
AB  - The biocompatibility of freeze-dried allogenic dentin powder and True Bone
      Ceramics (TBC), the latter prepared by incineration of bovine bone, as apical
      barrier materials was evaluated histopathologically in dogs. After pulpectomy, 80
      root canals of 53 dog premolar teeth were prepared, and each material was tightly
      packed to the apical stop area. The remainder of the canal was filled with
      guttapercha by the lateral condensation method. Control teeth were filled by the
      lateral condensation method using gutta-percha without constructing apical
      barriers. In both the teeth filled with the dentin powder and those filled with
      TBC, multinucleate giant cells appeared on the bone resorption surface and the
      surface of the root canal wall, and marked bone resorption and positive tartrate
      resistant acid phosphate staining were observed. Hard tissue had formed on the
      root canal wall and the filling material after 3 months. These findings suggest
      that the test materials are nonirritative and compatible with periapical tissue,
      and that they may be useful and clinically applicable as apical barrier
      materials.

PMID- 9922745
TI  - Coronal leakage: endotoxin penetration from mixed bacterial communities through
      obturated, post-prepared root canals.
AB  - Coronal leakage has been considered as one of the major causes of failure in root
      canal treatment. Bacteria have been shown to penetrate the root canal obturating
      materials and influence the periapical tissues. Endotoxin, a component of Gram
      negative bacteria, is a potent inflammatory agent and may be able to penetrate
      obturating materials faster than bacteria. This in vitro study examined the
      possible penetration of post-prepared canals by endotoxin and bacterial cells
      derived from mixed bacterial communities. Results showed that both bacteria and
      endotoxin were able to penetrate the obturating materials in post-prepared
      canals; however, endotoxin penetration was faster than bacterial. If one
      speculates that a similar sequence of events occurs clinically, then such a rapid
      penetration of endotoxin could lead to an early periapical reaction, with
      subsequent treatment failure and need for retreatment or periapical surgery. The
      need for an immediate and proper coronal restoration after root canal treatment
      is therefore reinforced.

PMID- 9922746
TI  - Comparative neurotoxic effects of root canal filling materials on rat sciatic
      nerve.
AB  - The neurotoxic effects of the root canal filling materials--Endomethasone, N2
      Universal, Traitement SPAD, Sealapex, and Calciobiotic Root Canal Sealer (CRCS)-
      were investigated on isolated rat sciatic nerves after local application. All of
      the canal filling materials reversibly inhibited the compound action potential
      (cAP) amplitudes. N2 Universal produced a 50% inhibition in 4.2 +/- 0.2 min.
      Traitement SPAD, Endomethasone, and CRCS produced the same inhibition in 6.4 +/-
      0.3, 6.5 +/- 0.2, and 6.6 +/- 1.1 min, and Sealapex in 9.2 +/- 2.0 min. The
      inhibitory effect of Sealapex decreased fastest, and 43% recovery of cAP
      amplitude was observed in 60 to 70 min. The inhibitory effects of Endomethasone,
      CRCS, and N2 Universal were more pronounced, and 10 to 20% recovery in cAP
      amplitudes were observed in 2 h. The inhibitory effect of Traitement SPAD was
      more persistent with 4% recovery in 2.5 h.

PMID- 9922747
TI  - Effects of CO2 laser in treatment of cervical dentinal hypersensitivity.
AB  - The effectiveness of CO2 laser therapy in the reduction and elimination of
      dentinal hypersensitivity in vivo and its thermal effects on tooth surfaces in
      vitro were investigated. Twenty-three patients with 91 sensitive teeth
      participated in this study and were followed for 3 months. The parameters used
      with CO2 laser were 1 W in a continuous wave mode and irradiation time ranging
      from 5 to 10 s. Hypersensitivity was assessed by thermal stimulus (a blast of air
      from a dental syringe). Thermal effects were measured by thermography using 10
      extracted human teeth. After laser treatment, all patients were immediately free
      from sensitive pain. Over 3 months, the CO2 laser treatment reduced dentinal
      hypersensitivity to air stimulus by 50%. All teeth remained vital with no adverse
      effects. Thermography revealed no temperature increase on irradiated tooth
      surfaces subjected to water coolant. These results show that the CO2 laser is
      useful in the treatment of cervical dentinal hypersensitivity without thermal
      damage to pulp.

PMID- 9922748
TI  - Host mediators in endodontic exudates. I. Indicators of inflammation and humoral
      immunity.
AB  - Exudate is often found in the root canal when entering the chamber and canal of
      teeth with periapical lesions. The aim of this study was to determine possible
      relationships between clinical or radiographic findings and the concentrations of
      different host mediators in endodontic exudates. Thirty-two nonvital teeth with
      periapical symptoms were included in the study. A Clinical Periapical Index was
      developed to quantify clinical findings. Endodontic exudates were collected with
      methylcellulose filter paper strips every 3 min, after opening of the pulp
      chamber. The concentrations of the lysosomal acid glycohydrolase beta
      glucuronidase, IgG, IgA, IgM, and interleukin-1 beta in the endodontic exudates
      were analyzed. The results demonstrated that exudates collected from teeth with
      suppuration (cloudy exudates), and teeth with higher periapical index scores
      (Orstavik et al., 1986) contained higher concentrations of beta-glucuronidase and
      interleukin-1 beta. Furthermore, when the periapical index indicated severe
      involvement, higher IgG was observed in the first samples. The exudates from
      patients who presented with a sinus tract or swelling contained higher
      concentrations of IgM, compared with the patients with only periapical
      sensitivity. Data showed that endodontic exudates from patient with endodontic
      lesions can be analyzed for host mediators, and differences in the mediators were
      seen with different clinical and radiographic symptoms.

PMID- 9922750
TI  - An evaluation of canal morphology at different levels of root resection in
      mandibular incisors.
AB  - One hundred randomly selected mandibular incisors were examined to assess the
      prevalence and location of two canals and to describe the canal anatomy that may
      be encountered during apical surgery. Sections of the root were cut at 1, 2, and
      3 mm from the apex, simulating a 20-degree beveled surgical resection. The
      sections were digitally imaged at x 50 magnification, and canal dimensions were
      measured using imaging software. The prevalence of two canals was 2% at 1 mm, 0%
      at 2 mm, and 1% at 3 mm. At these levels in the roots, the canal was rarely
      divided by hard tooth structure. An isthmus of tissue was present 20% of the time
      at 1 mm, 30% at 2 mm, and 55% at 3 mm. Four distinct canal types were noted: (i)
      round, (ii) oval, (iii) long oval, and (iv) ribbon. In 75% of the teeth, the
      canal shapes varied from one level to the next. The more coronally the root-end
      resection was made, the more elongated the canal tended to become.

PMID- 9922749
TI  - In vitro evaluation of the cytotoxicity and genotoxicity of root canal medicines
      on human pulp fibroblasts.
AB  - An intracanal medicine is often required because microorganisms in the dentinal
      tubes may be difficult to eliminate completely by instrumentation. Phenolic
      compounds are widely used in dental treatment as sedatives for the dental pulp or
      as disinfectants for caries and the root canal. In this study, propidium iodide
      fluorescence and DNA precipitation assay were used to investigated the cytotoxic
      and genotoxic effects of camphorated phenol and camphorated parachlorophenol on
      cultured human pulp fibroblasts in vitro. Both medicines reduced the content of
      double-stranded polynucleic acid of fibroblasts over a 24-h culture period in a
      concentration-dependent manner. Camphorated parachlorophenol was more cytotoxic
      than camphorated phenol. But, both medicines did not cause genotoxicity on pulp
      cells. The advantage of these experimental methods are simplicity and rapidity.
      Furthermore, this experimental system may be useful for preliminary cytotoxicity
      and genotoxicity screening of various dental medicines in vitro.

PMID- 9922751
TI  - A clinical study using the collagen gel Zyplast in endodontic treatment.
AB  - The use of a collagen gel as a hard tissue induction material in fractured and
      undeveloped teeth is reviewed. Three of four cases demonstrate a modest amount of
      hard tissue formation within the pulp space previously occupied by the collagen
      gel. Limitations in positive results, compared with a previous animal study and
      one clinical case report, are probably due to the pre-existence of infection in
      the present study.

PMID- 9922752
TI  - Flare-up rate in pulpally necrotic molars in one-visit versus two-visit
      endodontic treatment.
AB  - This retrospective study compared one-visit versus two-visit endodontic
      treatment. The same technique and materials were used before and after making the
      sole change to one-visit endodontic treatment in 1991. Treatment records of 402
      consecutive patients with pulpally necrotic first and second molars were
      compared. In 201 patients, treatment was provided by debridement and
      instrumentation, followed by obturation at a second visit; whereas the second
      group received single visit therapy. Flare-ups were defined as either patient
      reports of pain not controlled with over-the-counter medication or as increasing
      swelling. Sixteen flare-ups (8%) occurred in the two-visit group versus six flare
      ups (3%) for the one-visit group. This showed an advantage for one-visit
      treatment at a 95% confidence level. In a second comparison, one-visit patients
      who had previously received two-visit treatment for a different pulpally necrotic
      molar served as their own control. No significant differences were present in
      this subgroup of 17 patients.

PMID- 9922753
TI  - A comparison of root surface temperatures using different obturation heat
      sources.
AB  - This study compared root surface temperatures produced during warm vertical
      obturation using the System B Heat Source (SB), the Touch 'n Heat device (TH),
      and a flame-heated carrier (FH). The root canals of 30 maxillary incisor,
      premolar, and mandibular incisor teeth were prepared; divided into three groups;
      and obturated using each heat source. A thermocouple placed 2 mm below the
      cementoenamel junction transferred the temperature rise on the external root
      surface to a digital thermometer. SB surface temperature rise was < 10 degrees C
      for all experimental teeth. TH temperature rise in maxillary incisors and
      premolars was < 10 degrees C; however, > 10 degrees C was observed for mandibular
      incisors. FH produced a > 10 degrees C surface temperature rise in all
      experimental teeth. The critical level of root surface heat required to produce
      irreversible bone damage is believed to be > 10 degrees C. The findings of this
      study suggest that warm vertical condensation with the SB should not damage
      supporting periradicular tissues. However, caution should be used with TH and FH
      on mandibular incisors.

PMID- 9922754
TI  - Macroscopic and microscopic aspects of incinerated teeth.
AB  - Fifty-eight premolars, extracted for orthodontic reasons, were incinerated for
      one hour in a furnace at temperatures varying from 150 degrees C to 1150 degrees
      C, increasing at 100 degrees C intervals. Between 150 degrees C and 700 degrees C
      the teeth changed from light yellow to bluish-white passing through brown. The
      scanning electron microscope showed that at 150 degrees C cracks appeared in the
      enamel, increasing in number as the temperature rose. At 450 degrees C the
      internal surface detached from the dentine and showed the same cracked surface as
      the exterior. Above 1100 degrees C the enamel fragments had a prismatic structure
      difficult to identify due to their melted structure. Dentine retained its tubular
      structure up to 1150 degrees C even when the tubules' diameter decreased at 700
      degrees C. The cementum cracked as the temperature increased. Certain cracked
      areas actually detached at 600 degrees C giving a corroded aspect to the cementum
      and the residual zones became irregular when the temperature rose and eventually
      at 1150 degrees C the cementum was no longer identifiable.

PMID- 9922755
TI  - Discrimination between restorative dental materials by their radiopacity measured
      in film radiographs and digital images.
AB  - The aim of this study was to investigate the possibility of differentiating
      between various dental restorative materials by means of their radiopacity. Ten
      extracted molars and ten canines/anterior teeth were selected for the study. In
      the molar group a class II cavity and in the canines/anterior teeth group a class
      III cavity were cut by airrotor. The cavities were coated with vaseline before
      filling with five molar- and three anterior tooth restorative materials in the
      following sequence: for molars: amalgam, light-cured composite, glass ionomer
      cement, reinforced glass ionomer cement and light-cured composite. After each
      filling sequence radiographs were taken of the teeth on conventional film
      (Ektaspeed Plus) and by two digital systems: a storage phosphor plate (Digora)
      and a ccd-based sensor (Sidexis). Density was measured in the films with a
      densitometer in three areas of "air", in three areas of the class II fillings and
      one area of the class III fillings. The same areas were measured in the digital
      images where the program calculated automatically the mean grey shade values. The
      density values obtained from the filling areas were taken as a proportion of the
      values obtained from the areas of "air". Statistically significant differences in
      material density when related to "air" density (Wilcoxon's test) were observed
      between all materials in film (p < 0.01 for molars and p < 0.02 for
      canines/anterior teeth). For Digora only half of the materials differed
      significantly which was also the case for the Sidexis system (none of the CF
      materials were significantly different). In conclusion, the molar filling
      materials could be distinguished with a high probability in film while the two
      digital systems were less reliable. The results may be useful in forensic
      dentistry.

PMID- 9922756
TI  - An inclusion technique for marking dentures.
AB  - The importance of placing identification markers in dentures is well documented
      and this paper describes a simple and inexpensive technique for doing it. Twenty
      marked upper acrylic simulated dentures and 20 controls (unlabelled) were
      constructed in a standardized mould. Clear laminated labels were produced in a P
      touch 300 electronic lettering system and contained both the patient's
      identification number and suffix ZA (international code for South Africa). The
      markings were both clear and aesthetically acceptable. Strength tests were
      carried out to establish the effect of the mark with the result that no
      significant difference (p70.05) was demonstrated. The routine marking of all
      dentures by this method is advocated.

PMID- 9922757
TI  - Person identification by means of a single unique dental feature.
AB  - The combination of restorative procedures, developmental or acquired defects, or
      abnormalities of teeth enables the forensic dentist to make a meaningful
      comparison of ante- and postmortem data in search of the identity of a person.
      Dental records are not always sufficiently accurate to supply 12 concordant
      points from which a positive identification can be made. Under certain
      circumstances a single feature may be so extraordinary or unique that it alone
      can be sufficient to make a positive identification. Two cases of identification
      in which only one unique feature was used are reported.

PMID- 9922758
TI  - Response to paper by Ohtani S, Yamada Y, Yamamoto I. Age estimation from
      racemization rate using heated teeth.

PMID- 9922759
TI  - The biologic concept for the use of enamel matrix protein: true periodontal
      regeneration.
AB  - Guided tissue regeneration procedures have been used successfully to reestablish
      periodontal attachment. However, this new attachment reportedly differs from the
      original attachment in strength and continuity. Enamel matrix proteins secreted
      by Hertwig's epithelial sheath play an important role in cementogenesis on roots
      and in the development of the periodontal attachment apparatus. Enamel matrix
      protein harvested from developing porcine teeth, or enamel matrix derivative
      (Emdogain), is reported to induce true periodontal regeneration (the attachment
      of new, acellular cementum to the underlying dentin surface). The results of
      experimental and clinical trials of Emdogain are reviewed, and the procedure for
      application of the material is described.

PMID- 9922760
TI  - The predictability of periodontal treatment as measured by tooth loss: a
      retrospective study.
AB  - OBJECTIVE: This study evaluated the predictability of periodontal treatment as
      measured by tooth loss in 114 patients. METHOD AND MATERIALS: The patients were
      selected for the study if they had been treated for moderate-to-advanced
      periodontitis and had received continuous periodontal maintenance every 3 to 6
      months for 5 years or longer. The patients averaged 53 years of age, were equally
      divided by gender, and were maintained an average of 12.5 years. Patients were
      retrospectively assigned, according to the number of teeth lost following active
      periodontal treatment, to the well-maintained group (96 patients, 0 to 3 teeth
      lost), downhill group (15 patients, 4 to 9 teeth lost), or extreme downhill
      (three patients, 10 to 23 teeth lost) group. Teeth were retrospectively assigned
      a questionable or hopeless prognosis. RESULTS: Of the 2,899 teeth present during
      maintenance care, 378 had a questionable prognosis because of furcation
      involvement, and 63 (16.7%) of these teeth were lost. Of the 529 nonfurcated
      teeth that had a questionable prognosis, 68 (12.9%) were lost during the
      maintenance phase of treatment. Ninety-six teeth were given a hopeless prognosis,
      and 32 (33.3%) of these teeth were lost. Surgical treatment of teeth with
      questionable or hopeless prognosis did not improve the retention of these teeth
      in the downhill and extreme downhill groups. CONCLUSION: The prognosis of a
      periodontally compromised tooth in individual patients in difficult to predict
      accurately. A hopeless prognosis is more accurate than a questionable prognosis
      in predicting tooth loss in these patients.

PMID- 9922761
TI  - The use of liners under amalgam restorations: an in vitro study on marginal
      leakage.
AB  - OBJECTIVE: Marginal leakage of amalgam restorations may lead to secondary caries
      and pulpal damage. The purpose of this study was to determine the effect various
      cavity liners might have on microleakage. METHOD AND MATERIALS: Mesio
      occlusodistal amalgam restorations with margins on enamel and dentin were treated
      with different liner materials (an adhesive system, a topical fluoride gel, a
      cavity varnish, and a glass-ionomer cement) in vitro. Following restoration, the
      teeth were submitted to thermocycling in a stained solution and sectioned to
      allow assessment of microleakage. RESULTS: On enamel, the control group (no
      liner) and the glass-ionomer-lined group had equivalent leakage scores and were
      superior to every other group. On dentin, only the glass-ionomer specimens had
      superior performance. The cavity varnish and fluoride-lined specimens exhibited
      the highest leakage scores. CONCLUSION: The use of liners does not reduce
      microleakage on amalgam restorations when the cavity margins remain on enamel. On
      dentin margins, a glass-ionomer liner can reduce microleakage.

PMID- 9922763
TI  - Electrosurgery in dentistry.
AB  - Electrosurgery has been used in dentistry for several decades, but the technique
      is not widely practiced. This article briefly explains the principles of
      electrosurgery and attempts to clear up some misunderstandings about the healing
      of electrosurgical wounds. Clinical application of electrosurgery for the
      management of some common oral conditions is also described.

PMID- 9922762
TI  - Simultaneous bleaching of vital teeth and an open-chamber nonvital tooth with 10%
      carbamide peroxide.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      bleaching a nonvital tooth with an open pulp chamber while simultaneously
      bleaching the other vital teeth with 10% carbamide peroxide. METHOD AND
      MATERIALS: Ten discolored nonvital teeth were treated. Each nonvital tooth was
      prepared as in the conventional "walking bleaching" fashion, so that the gutta
      percha was sealed from the pulp chamber. The 10% carbamide peroxide was injected
      into the chamber of the nonvital tooth and loaded into the custom-fitted tray for
      all teeth. The nonvital teeth were bleached from both the inside and the outside.
      The patient closed the orifice with a cotton pellet during the day and changed
      the cotton pellet after meals. The patient applied fresh solution nightly.
      RESULTS: All teeth were successfully lightened. The time required to lighten the
      nonvital tooth was related to the duration of the discoloration. CONCLUSION: With
      proper patient selection and education, this technique can provide an effective
      way to lighten nonvital and vital teeth simultaneously, especially where extended
      treatment time may be required for difficult discolorations.

PMID- 9922764
TI  - Duplication and dilaceration of a crown with hypercementosis of the root
      following trauma: a case report.
AB  - Trauma to a primary mandibular central incisor resulted in a rare case of
      dilaceration and duplication of crown with hypercementosis of the root in the
      permanent successor. This tooth was extracted. This article highlights the
      consequences of trauma to a primary tooth for a developing permanent successor.

PMID- 9922765
TI  - Integrated orthodontic, surgical, and prosthodontic treatment of advanced
      malocclusion.

PMID- 9922766
TI  - When is caries caries, and what should we do about it?
AB  - Treatment of initial caries, albeit an everyday occurrence for the dental
      practitioner, presents considerable demands of patient assessment and diagnosis.
      Whatever decisions are made--to restore caries or to attempt to arrest its
      progress--the adoption of a maintenance program is of paramount importance.
      Patient motivation, in respect to dietary control and satisfactory oral hygiene,
      is central to a successful outcome, and in the future, practice management
      programs may include RAC as a diagnostic aid. New methods of caries management
      are more dynamic than traditional methods and place restoration of the lesion
      toward the bottom of the list of possible treatments, with the biologic rather
      than the mechanistic approach being a priority. However, the teaching of RAC in
      dental schools and the third-party funding of diagnostic tests and diagnosis are
      also required to reflect the increasing complexity of management of initial
      caries. If restorative intervention is indicated following diagnosis and RAC,
      treatment of initial caries should involve a minimal-intervention adhesive
      technique.

PMID- 9922767
TI  - [Chemoradiotherapy: history and state of the art].
AB  - The idea of combining radiotherapy and chemotherapy goes back to the very
      beginning of the antimitotic drugs era. At that time, this association was mainly
      based on a simple concept: spatial cooperation. The first period was one of so
      called "adjuvant" (post-irradiation) chemotherapy, soon followed by the once
      fashionable "neo-adjuvant" chemotherapy era. Today, concomitant administration of
      both therapies, mainly based on radiosensitization, appears promising, although
      the previous schemes were clearly efficient for some specific indications. In
      1998, radiochemotherapy combinations represent an unavoidable part of the
      anticancer strategy. A number of them have been recognized as the standard
      treatment for some localizations, and there is little risk to imagine that this
      number will increase within the next decade.

PMID- 9922768
TI  - [Biological principles of chemoradiotherapy].
AB  - Radio-chemotherapy combinations, especially their concomitant associations, are
      widely used in the treatment of cancer. The development of these associations has
      been so far related more to clinical research than to laboratory experiments. The
      biological basis of the use of these agents relies on their complementarity which
      concerns the cellular and molecular mechanisms involved in lethality (hypoxia,
      sensitivity throughout the cycle, DNA repair, apoptosis), spatial and temporal
      cooperation, etc. Laboratory experiments can determine favorable conditions for
      additivity, or supra-additivity, but also for infra-additive interactions as well
      as real antagonism which should be avoided in the clinic. It is however often
      difficult to transfer this information into the clinic since the conditions which
      allow additivity or supra-additivity are generally very narrow, and unlikely to
      be realised in the patient. General clinical conditions are more compatible with
      infra-additive interactions.

PMID- 9922769
TI  - [Randomizations!].

PMID- 9922770
TI  - [Clinical evaluation of concomitant chemoradiotherapy and practical
      recommendations].
AB  - The efficacy of concurrent radiochemotherapy should be evaluated in term of
      therapeutic ratio. The aims of treatment are increasing local control and
      possibly overall survival. Acute toxicity should be reported using the WHO
      recommendations, while late toxicity is reported using the scales recommended by
      the EORTC and RTOG Radiotherapy Groups. Moreover, functional, esthetic and
      quality of life considerations should be introduced. The application of these
      treatments needs a well-designed multidisciplinary staff.

PMID- 9922771
TI  - [Local control of the primary tumor. Necessary step in control of cancer].
AB  - There is clear evidence for a cancer cure. The hypothesis behind a treatment with
      curative intent is the ability to eradicate all the cancer cells of a tumour. Out
      of three cancer deaths, one is related to local failure. In some cancers like
      breast carcinoma, death is mainly in relation with the development of distant
      metastases. Even in such a tumour, an improvement in local control can translate
      as better survival. Radiation therapy, often in association with surgery, is
      playing a major role in tumour local control. Such a local control is mandatory
      if cure is at aim. One of the main goals of clinical research is to find a good
      compromise between local control of the disease and a non mutilating surgical
      approach.

PMID- 9922772
TI  - [Concomitant chemoradiotherapy and malignant glial tumors in the adult].
AB  - The prognosis of adult patients with malignant gliomas remains poor despite
      advances in neurosurgery and radiotherapy. Even if chemotherapy has done little
      to improve on these results, except in the treatment of oligodendrogliomas, many
      authors have proposed to test the effect of radiotherapy by adding concomitant
      chemotherapy. Unfortunately, the analysis of these studies is difficult because
      all these protocols are different with a small number of patients. Furthermore,
      there are only a few studies evaluated in well controlled clinical trials with
      homogeneous patient population. Important factors such as tumor grade, patient
      age, and Karnofsky score, which have a strong influence on survival in malignant
      gliomas, are not clearly evaluated. Whatever, all these studies suggest that
      concomitant radio-chemotherapy seems not be promising in the treatment of
      malignant gliomas.

PMID- 9922773
TI  - [Chemoradiotherapy of carcinomas of the upper aerodigestive tract].
AB  - The objective of this study was to review randomized trials which evaluated the
      effect of the radio-chemotherapy in head and neck carcinoma, and which compared
      radiotherapy alone vs the same local treatment plus chemotherapy. Over 40 such
      randomized trials have been performed, which generally showed no statistical
      difference between both arms. However few trials showed a benefit which is almost
      always in favor of the CT arm. Indeed, some trials of concomitant
      chemoradiotherapy have shown a statistically significant benefit in favor of the
      combined treatment. On the contrary, neoadjuvant chemotherapy generally leads to
      no detectable benefit compared to radiotherapy alone. These results have been
      reinforced by those of four randomized trials comparing neoadjuvant
      chemoradiotherapy and the same chemotherapy but given concomitantly with
      radiotherapy. The global effect of chemotherapy on survival of patients with head
      & neck squamous cell carcinoma has been recently evaluated by a meta-analysis
      based on individual patient data which included more than 10,000 patients from 63
      randomized trials. The absolute survival rate benefit at 5 years is 4%, but is
      more pronounced in the concomitant combinations (8% at 5 years). In tumors
      classified as "T3" of the pharyngo-larynx, neoadjuvant chemotherapy followed by
      radiotherapy in good responders can avoid a total laryngectomy without
      significantly compromised survival. In the nasopharynx carcinoma, a few
      randomized studies have been performed, suggesting a benefit in favor of
      chemoradiotherapy. Finally, future randomized trials will determine what are the
      optimal chemoradiotherapy schedules, as well as determining what is the best
      radiotherapy (accelerated, hyperfractionated) to use in combination with
      chemotherapy.

PMID- 9922774
TI  - [Concomitant chemoradiotherapy of cancer of the esophagus].
AB  - Radiation therapy with concomitant chemotherapy is the standard treatment for non
      resectable esophageal carcinoma. For patients with operable tumors, surgery is
      the traditional treatment. However several data have suggested that preoperative
      chemo- and radiotherapy could improve therapeutic results. At the present time,
      no randomized trial has demonstrated, except for adenocarcinoma of the cardia,
      the benefit of preoperative treatment. Other randomized trials are needed to
      determine the role and the optimal modalities of these treatments. This is a
      review of the literature data in concomitant chemotherapy and radiation in the
      management of esophagus.

PMID- 9922775
TI  - [Concomitant chemoradiotherapy in the therapeutic strategy of adenocarcinoma of
      the exocrine pancreas and stomach].
AB  - The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival
      rate lower than 5%. Resection, the gold standard treatment, can be performed in
      less than 10% of patients. Following surgery, the median survival is 12 months
      for the most favorable cancer patients. Concomitant chemoradiation, as an
      adjuvant treatment is superior to surgery alone, in terms of survival; controlled
      trials are currently performed. Neoadjuvant chemoradiation is a new approach,
      potentially able to increase survival and resection rate. This work justifies the
      role of these schemes, in terms of modalities and potential advantages. A second
      part is dedicated to gastric carcinoma, with a review of the current results of
      chemoradiation, whose efficiency, even though a trend can be observed, remains to
      be proven. Prospective adjuvant combined treatments are ongoing, in France and in
      the States.

PMID- 9922776
TI  - [Adjuvant chemoradiotherapy of cancers of the rectum].
AB  - Increasing local control remains a major endpoint in the adjuvant setting of
      rectal cancer. Postoperative concurrent 5FU-based chemotherapy and irradiation
      demonstrated its value in Duke's B and C patients. Toxicity decreased from the
      first studies to the current one's in relation with better radiotherapy
      technique, reduction of chemotherapy duration and quality assurance programs.
      Because preoperative irradiation alone has demonstrated its value on local
      control and overall survival, preoperative combined chemoradiotherapy should be
      investigated. Phase III trials are ongoing comparing preoperative
      radiochemotherapy to either preoperative irradiation alone or to postoperative
      radiochemotherapy. At this moment, if the patient has been operated,
      radiochemotherapy and additional chemotherapy should be offered in the case of
      Duke's B-C tumor. On the other hand, it should be preferably offered preoperative
      radiotherapy in case of T3 resectable T4 and hopefully in the context of a
      controlled clinical trial investigating preoperative concurrent
      radiochemotherapy.

PMID- 9922777
TI  - [Chemoradiotherapy in treatment of cancer of the anal canal].
AB  - In the treatment of anal canal carcinoma, since the work of Nigro, the 5
      fluorouracil-mitomycin C regimen is considered standard when applied
      concomitantly with radiotherapy. Surgery is used mainly to salvage the failures
      after irradiation. Two randomized European trials (EORTC, UKCCCR) have shown that
      the 5-fluorouracil-mitomycin C combination improves local control but not overall
      survival. The RTOG-ECOG trial has shown that mitomycin C improves local control
      when compared to 5-fluorouracil alone. This chemotherapy is responsible for a
      toxic death in 2% of cases. The 5-fluorouracil-cisplatin regimen will possibly
      represent an alternative to the 5-fluorouracil-mitomycin C. Ongoing trials will
      help to answer this question.

PMID- 9922778
TI  - [Concomitant chemoradiotherapy of infiltrating cancers of the bladder].
AB  - Until now, radical cystectomy has been considered the most effective treatment
      for invasive bladder cancer. However it fails to cure more than 50% of patients
      and can result in a mediocre quality of life. In an effort to improve cure rates,
      combined modality regimens have been investigated. Despite the preliminary
      results of early clinical trials, randomized trials have most often failed to
      show any benefit from neoadjuvant or adjuvant chemotherapy or radiotherapy. One
      of the major progress brought by radiotherapy has been the wide use of
      conservative treatment in several cancer, and in the recent years promising
      results have been published with concomitant radio-chemotherapy. The use of
      conservative approach in bladder cancer now appears to be a tangible reality for
      selected patients, but this combined modality have not yet been tested in
      randomized trials.

PMID- 9922779
TI  - [Chemoradiotherapy in cancers of the uterine cervix].
AB  - Treatment of uterine cervix carcinomas is based on radiotherapy and surgery.
      Prognosis of advanced carcinoma leads to the proposal of many combinations. Only
      concurrent radio-chemotherapy demonstrated some interests. Combination of
      radiotherapy and radiosensitisers failed to demonstrate any advantage and in some
      instances was associated with an adverse effect. Hydroxyurea and mitomycin C
      alone or associated were extensively tested without benefit. From modern
      combinations and recent studies, we could conclude that only cisplatin (and
      probably its derivates) can be included in future trials.

PMID- 9922780
TI  - [Respective roles of radiotherapy and chemotherapy in adjuvant treatment of
      cancer of the breast: theoretical importance and feasibility of
      chemoradiotherapy].
AB  - Concomitant radiochemotherapy is of potential interest in the treatment of early
      stage breast cancer. Radiotherapy improves local control after both conservative
      surgery and mastectomy and in this last case also improves overall survival. Some
      questions however still exist concerning the role of the delay between surgery
      and radiotherapy on the efficacy of this treatment. Over 6 months, the benefit
      due to radiotherapy could be reduced. Adjuvant chemotherapy leads to improved
      survival in all categories of patients with breast cancer, either with or without
      axillary-node involvement. Anthracyclin-containing regimens seem to be the most
      efficient, but their superiority on "historical" standard regimens such as
      cyclophosphamide-methotrexate-5-fluorouracil has never been fully established.
      Chemotherapy and radiotherapy have synergistic effects. Used simultaneously,
      their effect on residual disease after surgery could be increased. Moreover, this
      therapeutic modality enables reduction of treatment duration as well as the delay
      between surgery and radiotherapy. Some studies have demonstrated the good
      tolerance of concomitant radiotherapy and FNC (5-fluoro-uracil, mitoxantrone and
      cyclophosphamide) or CMF. Three French randomized trials testing the value of
      concomitant vs sequential radiotherapy + chemotherapy are ongoing. However,
      careful and critical interpretation of survival data will be required to consider
      concomitant chemoradiotherapy as a standard adjuvant treatment of early stage
      breast cancer.

PMID- 9922781
TI  - [Managing cutaneous melanoma].
AB  - Cutaneous melanoma represents the main cause of death among skin cancers. Early
      diagnosis gives, for the time being, the only possibility for high rate of
      curative treatment. Diagnosis is based on pathological findings, and at primary
      tumor stage. Breslow thickness of the lesion is the best prognostic index. At
      local stage of the disease, treatment is precisely codified by international
      recommendations and consensus conferences. Follow-up after surgical treatment is
      also well codified. Treatment of lymph node invasion or metastatic disease is, on
      the other hand, less codified. Despite recent advances, especially in
      immunotherapy, treatment of advanced stages of melanoma remains difficult.

PMID- 9922782
TI  - [Chemotherapy of soft tissue sarcoma in the adult].
AB  - The goal of postoperative treatment in adult soft tissue sarcoma is local
      control, and in high-risk patients prevention of distant failures. Radiation
      therapy is essential after non-radical surgery. The role of adjuvant chemotherapy
      on improvement of overall survival remains to be evidenced; however, recent meta
      analysis data have confirmed its impact on both local and metastatic evolution of
      the disease. Because for both radiotherapy and chemotherapy, delay of treatment
      may be crucial for efficacy following tumor excision, concomitant
      radiochemotherapy should be considered. Review of the literature as well as
      personal results showed the feasibility of postoperative radiochemotherapy in
      adult soft tissue sarcoma, even when the chemotherapeutic associations used
      included an anthracycline. Prospective study of radiochemotherapy should be
      performed in order to assess its real impact in terms of efficacy and toxicity.

PMID- 9922783
TI  - [Combined chemoradiotherapy of tumors in the child].
AB  - The high chemosensitivity of pediatric tumors along with their natural propensity
      for an early distant dissemination have stimulated the interest for chemo
      radiation combinations in children since the mid 50s. Following the early
      experiments in nephroblastomas on the interaction of Actinomycin-D and
      radiotherapy, multiple national and international studies have been conducted
      since the mid 70s with considerable success: nowadays most pediatric tumors enjoy
      a long term survival in excess of 70%. Like their adult counterparts, these
      associations aim to induce an early control of the primary tumor and distant
      spreading (spatial cooperation) but also, more specifically in children, to limit
      the toxicity on normal tissues when treatment intensity can be further reduced.
      The association of an initial chemotherapy followed by local radiation at a dose
      and in a volume adapted to the response to chemotherapy along with associated
      prognostic factors has become widely tested in national and international studies
      conducted in Hodgkin's disease, Ewing's sarcoma, medulloblastomas, and brain
      tumors in the very young. Conversely, concomitant associations have remained
      limited to high-risk subgroups (parameningeal rhabdomyosarcomas for example) due
      to their potential hazards.

PMID- 9922784
TI  - [Does neoadjuvant chemotherapy have a place in treatment with curative intent of
      local or locoregional stage cancer?].
AB  - Neoadjuvant chemotherapy is aimed to allow tumor debulking, organ sparing
      treatment and survival increase. Neoadjuvant chemotherapy has proven its ability
      to perform conservative treatment in breast, head and neck, bladder, oesophageal
      cancers and osteosarcoma. It has not yet proven its impact on overall survival.
      Neoadjuvant chemotherapy requires further studies.

PMID- 9922785
TI  - [Cancer of the esophagus: outcome of neoadjuvant therapy on surgical morbidity
      and mortality].
AB  - Prognosis of oesophageal cancer is poor. There have been phase II-III trials of
      postoperative chemotherapy with the aim of improving survival. Chemoradiotherapy
      seems more promising than both chemotherapy and radiotherapy alone. In contrast,
      better results obtained with chemoradiotherapy were associated with an increase
      in morbidity and mortality, and finally overall survival was uncommonly improved.
      It is necessary to implement new multidisciplinary randomised trial.

PMID- 9922786
TI  - [Pancreatectomy after neoadjuvant chemoradiotherapy for potentially resectable
      exocrine adenocarcinoma of the pancreas].
AB  - The last of the therapeutic modalities proposed for exocrine adenocarcinoma of
      the pancreas which appears to be potentially resectable, neoadjuvant
      chemoradiotherapy has many prerequisites: validation of the diagnosis,
      determination of resectability with a high degree of confidence and palliation of
      biliary obstruction when present. This rather complex strategy does not seem to
      have major deleterious effects on the operative procedure or the postoperative
      course. Only multicentric protocols will, in the near future, give an answer to
      the question of secondary toxic effects and improvement of survival of this new
      therapeutic strategy.

PMID- 9922788
TI  - [Combined curietherapy and chemotherapy].

PMID- 9922787
TI  - [Radiation sensitizing agents for hypoxic cells: past, present and future].
AB  - Hypoxic cells are present in rodent and xenografted human tumours and it has been
      known for a long time that the absence of oxygen in tumours is a factor of
      resistance against ionising radiation. The dose modifying role of oxygen (oxygen
      enhancement ratio) has been largely studied in experimental models. For pO2
      values of 2 mmHg, the relative radiosensitivity of tumour cells is intermediate
      between the maximum sensitivity observed in air and the minimal one observed in
      hypoxia. The measurement of tumour pO2 in patients (polarographic technique) has
      demonstrated the presence of low values (< 10 mmHg) in many different tumour
      sites (ENT, uterine cervix, breast, melanoma, etc). In order to sensitise hypoxic
      tumours, imidazole have been used in patients, but most of the results were
      negative. New methods have been developed in the combination of bioreductive
      drugs of cytotoxic cells to radiotherapy. In this article, we will describe the
      clinical results obtained in patients with radiosensitising chemical agents.

PMID- 9922789
TI  - [Current studies of combined radiotherapy-hormone therapy in localized and
      locally advanced prostatic cancers].
AB  - In locally advanced prostate cancer three clinical randomized trials have shown
      that external irradiation combined with LHRH analogue with or without
      antiandrogen improved survival: disease-free survival, local recurrence-free
      survival, metastasis-free survival (P < 0.001). EORTC trial 22863 alone has shown
      a significant improvement of overall survival (P = 0.001), with an LHRH analogue
      (goserilin acetate, zoladex) started the first day of irradiation and followed
      every 4 weeks for 3 years; for RTOG trial 85-31 the same LHRH analogue started
      during the last week of irradiation and given until relapse increases survival of
      patients with poor differentiated tumours with gleason score ranging from 8 to 10
      (P = 0.03). In locally confined prostate carcinoma randomized trials are ongoing
      to assess the impact of conventional irradiation or three dimensional conformal
      radiotherapy with or without adjuvant hormonotherapy.

PMID- 9922790
TI  - [Are too many antidepressants being prescribed in France?].

PMID- 9922791
TI  - [Depression in the aged: diagnosis and treatment].
AB  - DIAGNOSIS: Recently published research has provided new elements for longstanding
      questions concerning depression in the elderly. The wide differences in
      epidemiological data are largely due to differences in the population studied and
      age-related changes in lifestyle. The relative proportions of syndromic and infra
      syndromic states of depression appear to be different in young adults and elderly
      adults. In addition, it has been demonstrated that non-specialized criteria
      cannot correctly identify depressive disorders in the elderly. Many different
      specific evaluation tools have been developed, but often the available
      instruments used are poorly adapted to the elderly. IN CLINICAL PRACTICE:
      Clinically, it is possible to distinguish between signs of depression, for
      example depressive states with a cognition dysfunction component and early phases
      of dementia, and normal manifestations of the aging process. Somatic signs lack
      specificity but rarely compromise diagnosis. Although the relationship between
      somatic signs and depression in the elderly is complex, our understanding is
      improving constantly. Unlike official taxonomies, certain authors describe
      geriatric depression as a nosologically distinct entity. TREATMENT: The probably
      underestimated need for treatment is directly related to prognosis. Treatment
      should include a psychotherapy component and a drug component. New better
      tolerated and less toxic antidepressors appear to be as effective as tricyclics
      and their derivatives. There is some concern however about side effects. Current
      research will determine whether they are as frequent as with the reference
      treatments. 10 ANTIDEPRESSORS: We discuss published data on 10 available
      antidepressors proposed for geriatric patients (viloxazine, mianserine,
      tianeptine, fluoxetine, moclobemide, paroxetine, citalopram, sertraline,
      minalcipran, venlafaxine).

PMID- 9922792
TI  - [Choice of an antidepressive agent].
AB  - A WIDE SELECTION: New drugs have recently been added to the list of antidepressor
      agents which includes more than 20 compounds in 1998. The mechanisms of action
      are quite different. MECHANISM OF ACTION: Better knowledge of each compound and
      its mechanism of action on the different monoamines functioning in the brain has
      not been sufficient to determine a pharmacoclinical classification of depression.
      Likewise, alone mechanism of action is insufficient for choosing the right drug
      for a given individual. CLINICAL SIGNS: Therapeutic decisions must also take into
      account the clinical and functional features expressed by the patient, focusing
      on the importance of the patient-physician relationship in treating patients with
      states of depression.

PMID- 9922793
TI  - [The risk of suicide].
AB  - HISTORICAL PERSPECTIVE: A certain number of historical elements including the
      progressive loss of religious values and the fact that suicide is considered to
      be an integral part of medical knowledge must be taken into consideration when
      assessing the risk of suicide. The sociological and psychoanalytical approaches
      attempt to help draw the suicidal subject out of the his/her personal implication
      by affecting the social and subconscious aspects of the problem respectively.
      Other elements such as psychiatric, sociocultural, biological and
      psychopathological factors are also involved in evaluating the risk of suicide.
      RISK FACTORS: Durkheim's analysis of the social, familial and occupational
      factors observed in suicide remains pertinent for assessing risk. Psychiatric
      disorders are also highly significant risk factors since some type of disorder is
      found in approximately 90% of all suicide victims. Affective disorders including
      rapidly alternating bipolar behavior, psychoses, particularly schizophrenia, and
      borderline personality are the most frequently observed, especially when
      associated with certain types of behavior such as drug or alcohol abuse. The risk
      related to other factors such as suicidal behavior (attempts or ideation) is
      independent of the psychiatric illness. For example, the risk of successful
      suicide is 30 greater the year after an attempted suicide than in the normal
      population. ASSESSING RISK: There are no known clinical means, notably
      psychometric, which can successfully predict the imminence of suicide. Recent
      studies on brain monoamine levels have shown that a lower 5-HIAA level does play
      some role in suicidal behavior, particularly violent suicide, although there is
      no predictive power for normality. It is important to recall that certain
      advances in the field of psychopathic illnesses offer new insight into concepts
      such as the death instinct and the suicidal act itself.

PMID- 9922794
TI  - [Current trends in the therapeutic use of thymic regulators].
AB  - LITHIUM: Current research in the field of dysthymia therapy is dominated by the
      discovery of alternatives to lithium. Lithium remains however the gold standard,
      whether used alone or combination with anti-seizure drugs such as carbamazepine,
      valpromide or valproate. The most recent data on lithium therapy emphasize the
      need for precaution in case of pregnancy. New interactions, particularly with
      converting enzyme inhibitors, have also been evidenced. Finally, like beta
      blockers, lithium should be tapered off progressively over a two-month period to
      avoid early relapse. OTHER TREATMENTS: New candidate drugs such as lamotrigine
      offer some promising perspectives. For severe states, long-term
      electroconvulsivotherapy can be proposed. Finally, drug therapy should be
      integrated into a structured psychotherapy program in order to favor the
      prevention of relapse and reduce the negative psychosocial consequences of mood
      disorders. Both the patient and close family and friends should participate in
      the psychotherapy; several methods have been developed with promising efficacy to
      be confirmed by controlled studies.

PMID- 9922795
TI  - [Re-evaluating neuroleptics: their antipsychotic properties?].
AB  - ANTIPSYCHOTIC PROPERTIES: Compared with traditional neuroleptics, antipsychotics
      affect receptors other than dopaminergic receptors, particularly serotonin
      receptors. Clinically, antipsychotics have little or no extrapyramidal effects
      and do not induce late dyskinesia. They are effective for productive symptoms. It
      is more difficult to evidence their antideficiency effect. Antipsychotics can
      improve certain cases of resistant schizophrenia. LIMITATIONS OF NEUROLEPTICS:
      Clinical response to traditional neuroleptics is not really satisfactory for
      approximately one quarter of the patients. In addition, problems of tolerance,
      particularly neurological disorders, are important. ATYPICAL NEUROLEPTICS:
      Sulpiride can be considered as a precursor. Amisulpride is a more recent
      derivative. Clozapine, risperidone and olanzapine are also distributed in France.
      Other compounds should be available soon. UNRESOLVED QUESTIONS: The long-term
      effect of these new drugs, whether similar to or superior to classical compounds,
      remains to be determined as well as their long-term safety profile. In addition,
      due to high cost, first line use of these new antipsychotics requires a cost/
      benefit analysis.

PMID- 9922796
TI  - [Follow up of a schizophrenic patient in general practice].
AB  - GEOGRAPHIC SECTORS: In France, the public psychiatric health care system is
      divided into geographic sectors. Each sector is attributed to a psychiatric team
      and health care institutions. Each psychiatric unit in public hospitals is
      responsible for a given sector. LEGAL FRAMEWORK: The legal framework for
      sectorialization was established in 1960 and has been completed by various
      administrative and legislative regulations which define the missions of the
      sector and application modalities. RESOURCE ALLOCATION: Changing attitudes in
      psychiatric care, therapeutic techniques and economic goals have had an effect on
      the notion of sectorialization. Current policies tend towards the development of
      intersector exchange to make better use of available resources and better meet
      the objectives of the public health care system.

PMID- 9922797
TI  - [Behavioral psychotherapy: possibilities in the framework of general medicine].
AB  - A SOLUTION FOR A COMMON PROBLEM: General practitioners regularly see patients
      with psychiatric problems. Cognitive and behavioral therapy offer reasonable
      complements or alternatives to drug therapy. Physicians should be aware of the
      possibilities and inform their patients. VARIOUS INDICATIONS: The principle
      indications are anxiety and depressive states, but indications can be widened to
      other areas such as psychological approach to health and behavioral medicine. A
      RECOGNIZED THERAPY: Cognitive and behavior psychotherapy offers a good
      cost/benefit ratio. More widespread use has been achieved by reinforcing
      university training.

PMID- 9922798
TI  - [Current trends in clinical psychiatric research].
AB  - SCHIZOPHRENIA: The long-standing dopaminergic hypothesis is based on well
      established findings, mainly related to a dysfunction of the mesolimbic C2 and D3
      receptors, negative signs of prefrontal hypodopaminergia concerning the D2 and D4
      receptors. Immune disorders are also involved as well as a possible
      neurodevelopmental component. Finally genetic factors play an important role.
      DEPRESSIVE STATES: Three monoaminergic systems appear to be implicated: the
      catecholaminergic, serotaminergic and homovanilic systems. It is not known
      whether the disorder of the serotaminergic system results from pre-existing
      fragilization or a symptom-related modification. HYPOTHESES CONCERNING
      DEPRESSION: According to the chronobiology hypothesis, certain biological rhythms
      (cortisol, temperature, perhaps melatonin) are desynchronized, a disequilibrium
      which disappears after cure. The fragilization hypothesis is based on the
      progressive development of a stress-related pathological organization in the
      hippocampo-hypothalamo-adrenal axis. PERSPECTIVES: The development of new
      psychotropes remains a challenge to meet the unsatisfied demands in psychiatrics.
      Drugs with rapid action and minimal side effects are needed.

PMID- 9922800
TI  - [How to recognize personality disorders in general medicine].
AB  - DEFINITION: The psychological traits characteristic of an individual define that
      person's personality. A personality disorder is considered to exist when it
      causes the person or his/her family or friends to suffer. Personality disorders
      are often associated with a state of depression, aggravating or prolonging it.
      FUNDAMENTAL ASPECTS: Histrionic, paranoid, obsessional and psychopathic
      personalities are the most well known types of personality disorders, but
      dependent and borderline personalities should not be overlooked. Cognitive and
      behavioral therapies are particularly useful in this field of health care.

PMID- 9922799
TI  - [Psychiatry today].
AB  - A COMMON SITUATION: Primary care physicians often provide care for schizophrenic
      patients. The main approaches include drug regimens, psychotherapy and
      psychosocial support. DRUG THERAPY: Neuroleptics should be given in single drug
      regimens in a continuous protocol for long periods. Side effects, particularly
      neurological effects, can be countered with antiparkinson medication. The aim is
      to reach the best possible balance between the therapeutic effect and side
      effects. PSYCHOTHERAPY: The general practitioner does not necessarily use
      sophisticated psychotherapeutic protocols but rather relies on a certain number
      of attitudes aimed at helping the patient accept the medications and control the
      main pathological mechanisms the schizophrenic state as expressed in the
      relationship with the health care provider. PSYCHOSOCIAL SUPPORT: A series of
      assistance measures (allocations for handicapped adults, adapted housing,
      protection of property) often involve a team of workers who should all take part
      in the therapeutic strategy.

PMID- 9922801
TI  - [Pharmacological management of failure of treatment with antidepressants].
AB  - Depression, a chronic disease and a leading cause of disability worldwide, will
      generate increasing needs in terms of public health in the coming years. Many
      antidepressants are now available. However, these molecules present real
      limitations and disadvantages. Thus there are great expectations on the part of
      the clinicians for more efficient drugs that are better tolerated. How can we
      satisfy such hopes and innovate in this domain today? One original and most
      promising strategy for developing new antidepressants that are more efficient and
      better tolerated involves antagonizing both alpha 2-noradrenergic and 5HT2 and
      5HT3 serotonergic receptors, without blocking 5HT1A serotonergic receptors. The
      technology now available in pharmacological research allows the development of
      such molecules.

PMID- 9922802
TI  - Oxidative modification of low-density lipoproteins in atherothrombosis.
AB  - Oxidative modification of LDL may occur via mechanisms, which are either
      dependent or independent of lipid peroxidation. Peroxidation of lipids in LDL,
      either initiated by radicals or catalysed by myeloperoxidase, results in the
      generation of aldehydes which substitute lysine residues in the apolipoprotein B
      100 moiety and thus in the generation of oxidised LDL. Phospholipase activity,
      prostaglandin synthesis and platelet adhesion/activation are associated with the
      release of aldehydes which induce oxidative modifications of LDL in the absence
      of lipid peroxidation and thus in the generation of malondialdehyde-modified LDL.
      Recently, we have demonstrated an association between coronary artery disease and
      increased plasma levels of oxidised LDL. The increase of circulating oxidised LDL
      is most probably due to backdiffusion of oxidised LDL from the atherosclerotic
      arterial wall in the blood and is independent of plaque instability. Indeed,
      plasma levels of oxidised LDL were very similar in patients with stable coronary
      artery disease and in patients with acute coronary syndromes. Acute coronary
      syndromes were, however, associated with increased release of malondialdehyde
      modified LDL that was independent of necrosis of myocardial cells. Indeed, plasma
      levels of malondialdehyde-modified LDL were very similar in patients with
      unstable angina and patients with acute myocardial infarction, in contrast with
      levels of troponin I which were significantly higher in acute myocardial
      infarction patients. These data suggest that oxidised LDL is rather a marker of
      coronary atherosclerosis whereas malondialdehyde-modified LDL is rather a marker
      of plaque instability and atherothrombosis. At present, in the absence of
      prospective studies, the causative role of oxidatively modified LDL in
      atherothrombosis is, however, not established.

PMID- 9922803
TI  - Effects of spironolactone-altizide on left ventricular hypertrophy.
AB  - OBJECTIVE: To investigate the effects of the association spironolactone (25
      mg)/altizide (15 mg) as monotherapy on left ventricular hypertrophy (LVH) in
      patients with mild to moderate hypertension. Additionally, to study the
      correlation between left ventricular mass (LVM) index and electrocardiographic
      (ECG) criteria for LVH. METHODS AND RESULTS: This was an open, prospective study
      of 6 months. Patients with mild to moderate essential hypertension were treated
      with spironolactone/altizide for two months and were included in the study if
      their blood pressure (BP) at the end of this first treatment period was
      normalised according to protocol criteria (systolic BP < 160 mm Hg and diastolic
      BP < 95 mm Hg). Patients then entered a second 4-month treatment period. LVM was
      determined by echocardiography performed at the beginning of treatment and after
      6 months. LVH was defined as LVM > or = 100 g/m2 in women and LVM > or = 131 g/m2
      in men. Echocardiograms were interpreted blindly by two echocardiography reading
      laboratories. Seventy-one patients with a normalised BP after two months of
      treatment, were enrolled in the study. Changes in LVM index were studied in 31/71
      patients with LVH (25 women and 6 men, mean LVM index +/- (SD) 119.9 +/- 16.4
      g/m2 in women and 147.8 +/- 10.9 g/m2 in men). Spironolactone/altizide
      significantly reduced LVM index by 10%, from 125.3 +/- 22.5 to 114.2 +/- 25.1
      g/m2 (p < 0.005). Posterior and septal wall thickness decreased by 4% (p = 0.06)
      and 5% (p = 0.026), respectively. End-diastolic dimension was reduced by 3%, from
      50.3 +/- 3.3 to 48.9 +/- 3.4 mm (p = 0.006). The posterior wall thickness to end
      diastolic dimension ratio remained unchanged. Complete regression of LVH
      according to mass criteria occurred in 11 patients out of 31 (34.5%). The
      observed changes in ECG voltage criteria were in accordance with a decrease of
      LVM index. CONCLUSION: In this open study, the potassium-sparing diuretic
      spironolactone/altizide decreases LVM index in hypertensive patients, who were
      selected for follow-up because they had echocardiographic LVH and because their
      BP had normalised during an initial 2-month treatment period.

PMID- 9922804
TI  - Plasma lipids, HDL and apolipoproteins, and coronary heart disease in men less
      than 50 years old. A case-control study.
AB  - OBJECTIVE: To determine the predictive value of lipoproteins for early coronary
      heart disease in men less than 50 years old from southern Europe. METHODS AND
      RESULTS: One hundred and fifty-seven men less than 50 years old were
      consecutively evaluated for symptoms of coronary heart disease in a tertiary
      referral hospital. A group of 415 male miners with mean age of 41 +/- 8 years
      without clinical or electrocardiographic evidence of coronary disease served as
      controls. Blood samples were taken by venipuncture as soon as possible after
      admission to the hospital from cases and after 12 hours of fasting in controls.
      Plasma concentrations of total cholesterol (TChol), HDL-cholesterol (HDLChol),
      triglycerides (TG), apoproteins A1 and B and Lp(a) were determined. The odds
      ratios, as estimators of relative risk, were computed using the Mantel-Haenszel
      procedure. The odds ratios from highest to lowest were a TChol/HDLChol ratio
      equal to or greater than 5: 10.7 (95% confidence interval (CI) 6.1 to 18.8), TG >
      2.25 mmol.l-1 and HDLChol < 0.9 mmol.l-1: 7.4 (95% CI 3.9 to 14.1), HDLChol < 0.9
      mmol.l-1: 6.9 (95% CI 4.5 to 10.6), TG > 2.25 mmol.l-1: 3.3 (95% CI 2.0 to 5.3),
      Lp(a) > 30 mg.dl-1: 2.7 (95% CI 1.8 to 4.1), Apo B > 120 mg.dl-1: 2.4 (95% CI 1.3
      to 4.2), non-HDLChol > 5.2 mmol.l-1: 2.2 (CI 1.4 to 3.3), TChol > 6.5 mmol.l-1: 1
      (95% CI 0.6 to 1.6), TChol > 5.2 mmol.l-1: 0.9 (95% CI 0.6 to 1.3). CONCLUSIONS:
      This study indicates that in males less than 50 years a ratio TChol/HDLChol > or
      = 5 presents the greatest risk power for early coronary heart disease. Plasma
      concentrations of TChol alone did not demonstrate to have value as risk factor
      for cardiovascular disease.

PMID- 9922805
TI  - Transient second-degree heart block during dipyridamole myocardial perfusion
      imaging.

PMID- 9922806
TI  - Ischaemic electrocardiographic changes after massive blood transfusion: findings
      based on myocardial scintigraphy using 99mTc-MIBI and 123I-MIBG.
AB  - We performed myocardial scintigraphy on a patient with ischaemic
      electrocardiographic changes after massive blood transfusion. Although there was
      no defect by 99mTc-MIBI scintigraphy, 123I-MIBG scintigraphy was observed
      suggesting denervation after massive blood transfusion. Myocardial scintigraphy
      using 99mTc-MIBI or 123I-MIBG can be useful for the evaluation of myocardial
      dysfunction with reversible myocardial infarction.

PMID- 9922807
TI  - Thrombotic thrombocytopenic purpura: a rare but potential life-threatening
      complication following ticlopidine administration.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a known, although rare, complication
      of ticlopidine treatment. It typically appears within the first days or weeks
      after initiation of therapy. We describe a case of TTP in a 75-year-old patient,
      due to ticlopidine, occurring three weeks after coronary stent implantation. The
      patient responded favourably to fresh frozen plasma exchanges. We are reporting
      this case to emphasize that prognosis depends on prompt diagnosis and early
      treatment, implying careful biochemical monitoring.

PMID- 9922808
TI  - Entrapment of a guide wire during percutaneous occlusion of a coronary artery
      fistula.
AB  - Coronary artery fistulas are extremely rare and coil occlusion by intervention
      techniques seems to be the therapy of choice. We describe the case of a 3-month
      old infant with a coronary artery fistula. During occlusion of the fistula a
      coronary guide wire got entrapped in a small coronary branch, but could be
      successfully retrieved with a microsnare without damage to the heart. The
      microsnare technique prevented rupture of the guide wire.

PMID- 9922809
TI  - Management of fulminant hepatic failure.
AB  - Fulminant hepatic failure is an infrequent but dreadful disease, occurring
      usually in young patients. Despite fulminant hepatic failure is reversible in
      most of the cases, some patients develop brain edema and intracranial
      hypertension, which are the most common cause of death in these patients. Liver
      transplantation significantly improves the prognosis of selected patients in who
      precise criteria predict a low chance of survival. This review summarizes the
      modern standard of care of patients with fulminant hepatic failure, with
      particular underlining of the management of brain oedema and intracranial
      hypertension.

PMID- 9922810
TI  - Posterior approaches in groin hernia repair with prosthesis: open or closed.
AB  - Laparoscopic herniorraphies have been used to reduce the pain and convalescence
      associated with open approaches. However, there is still not any consensus of the
      best approach. We compared open preperitoneal and laparoscopic total
      extraperitoneal approaches in groin hernia repair. METHODS: Thirty-two patients
      underwent open preperitoneal herniorraphy (Group I) and other 32 patients
      underwent total extraperitoneal repair (Group II). Time of surgery was noted.
      Visual Analogue Scale (VAS) was applied to evaluate the postoperative pain
      intensity. RESULTS: Operation time was 35 (20-65) minutes in Group I and 58 (40
      85) minutes in Group II (p < 0.05). The difference of complication ratios between
      two groups was not significant. Laparoscopic approach was associated with less
      pain within postoperative 24 hours as compared to the open technique. However,
      after the first postoperative day, there was no longer statistically significant
      difference between both groups. No recurrence has yet been seen in follow-up
      period of 15 (4-24) months. CONCLUSION: Laparoscopic herniorraphy is associated
      with better results in term of postoperative pain within the first 24 hours as
      compared to open technique.

PMID- 9922811
TI  - The effect of intestinal transit time on bacterial translocation.
AB  - Increase in intraluminal bacterial count, disruption of the mucosal integrity,
      changes in intestinal immunity and transit time are the factors involved in
      bacterial translocation. The relationship between intestinal transit time, intra
      luminal bacterial count and translocation rate were investigated in 40 Wistar
      albino rats. The study was conducted in 4 groups with 10 animals in each. Group I
      (controls): saline + laboratory chow, Group II: saline + oral total parenteral
      nutrition (TPN) solution, Group III: morphine sulfate (MS) + oral TPN solution,
      Group IV: neostigmine bromide (NB) + oral TPN solution. Intestinal transit time
      was measured by using Indium111-labeled diethylene triamine pentaacetic acid
      (DTPA). It was prolonged in the MS-treated group and shortened in the NB-treated
      group (p < 0.01). The frequency of bacterial translocation was 60% in the oral
      TPN solution group, 100% in the MS-treated group, 20% in the NB-treated group and
      10% in controls. Bacterial counts in duodenum, jejunum, ileum and caecum were
      significantly increased (p < 0.001) in the MS-treated group and decreased (p <
      0.05) in the NB-treated group in comparison with the control group. In
      conclusion, the prolongation of intestinal transit time increased the
      intraluminal bacterial count and augmented bacterial translocation. The decrease
      in intestinal transit time had a converse effect.

PMID- 9922812
TI  - Recurrent supra-anastomotic aneurysm following infrarenal aortic repair.
AB  - A 72-year-old woman presented with a recurrent proximal aortic true aneurysm 7
      years after an abdominal aortic aneurysmectomy. It was complicated by a contained
      rupture into the right psoas. The repair was successfully realized through a
      thoraco-abdominal approach. A tube graft was interposed between the proximal
      aorta and the old graft, associated with the reimplantation of the renal
      arteries. A systemic follow-up of abdominal aortic grafts by reliable diagnostic
      methods is advocated to provide a timely and appropriate surgical treatment of
      this major complication.

PMID- 9922813
TI  - Pathologic fractures due to metastatic disease. A retrospective study of 160
      surgically treated fractures.
AB  - Orthopaedic surgeons are increasingly confronted with metastatic fractures. As
      the majority of metastatic fractures never heal, surgical treatment is required.
      The goals of surgical therapy are to achieve early mobilization, relief pain and
      improve quality of life. One hundred twenty nine patients with 160 metastatic
      fractures of a long bone, completed or impending, were retrospectively analysed
      with regard to the type of treatment, effect on pain relief and mobility. Seven
      of the patients (4.4%) died postoperatively, a good functional result was
      obtained in 86.9% of the cases and for all patients a good analgesic effect was
      achieved. In 3.75% of the cases a mechanical complication was seen which needed
      reintervention. In general, the only indication for endoprosthesis is an
      intracapsular or very proximal lesion. In almost all other cases, intramedullary
      nailing is preferred.

PMID- 9922814
TI  - Leiomyosarcoma of the mesocolon.
AB  - Retroperitoneal sarcomas are rare tumours. Although exceptional in the mesocolon,
      they can yet be considered as a special kind of retroperitoneal tumours.
      Leiomyosarcoma represents from 25 to 30% in this location. Clinical features are
      rarely obvious because the symptomatology depends upon displaced or compressed
      adjacent organs. Most authors agree on using the CT-scanner or MRI as diagnostic
      tools. However, the diagnosis is made after a histologic examination permitting
      the establishment of its grade and margins. Only a surgical treatment can offer
      prolonged survival and this can be improved if there is a low histological grade
      and total excision. The mesocolic location facilitates a radical removal and may
      therefore offer a better long-term prognosis.

PMID- 9922815
TI  - Intracaval extension of a recurrent low-grade endometrial stromal sarcoma.
AB  - We report the case of a patient undergoing successful removal of an intracaval
      extension of a recurrent low-grade endometrial stromal sarcoma sixteen years
      after complete surgical resection. Low-grade endometrial stromal sarcoma is rare
      uterine neoplasm with a excellent 5-year survival but with high incidence of
      relapse after a very long time. The tumour has a tendency for lymphatic and
      venous extension. Intracaval extension is an exceptional indication to perform
      caval surgery in the treatment of malignant neoplasm.

PMID- 9922816
TI  - Transaortic coronary patchplasty for isolated main left coronary ostial stenosis:
      a report of five cases.
AB  - The incidence of isolated ostial stenosis of the left main coronary artery varies
      between 0.13% and 2.7%. We performed surgical ostial angioplasty in five patients
      who had isolated left coronary ostial stenosis. One patient had low systemic
      blood pressure and, after the procedure, manifested myocardial ischaemia:
      conventional aortocoronary bypass was performed. The outcome of the four others
      was uneventful. They remained free of symptoms and resumed normal activities.
      Transaortic patch angioplasty might be useful operative method for the isolated
      coronary ostial stenosis, since it restores a more physiologic perfusion of the
      coronary arteries.

PMID- 9922817
TI  - The use of extracorporeal membrane oxygenation in postpneumonectomy pulmonary
      oedema.
AB  - A 59-year-old male developed a severe adult respiratory distress syndrome
      following a right pneumonectomy for pulmonary cancer. Extracorporeal membrane
      oxygenation for 11 days was life-saving. The operation was considered curative,
      but the patient died nine months later with multiple metastases. The pathogenesis
      and treatment for postpneumonectomy pulmonary oedema and an explanation for rapid
      dissemination of the cancer are stated.

PMID- 9922818
TI  - Endogenous dopamine-derived neurotoxins and Parkinson's disease.

PMID- 9922819
TI  - Clinical relevance of the determination of anti-GQ1b antibodies in Miller Fisher
      and Guillain-Barre syndromes.
AB  - Anti-GQ1b antibodies were assayed by an enzyme-linked immunosorbent assay in sera
      from patients with non-neurological disorders (N = 20), and with various
      neurological disorders (N = 59), including nine cases of Miller Fisher syndrome,
      16 cases of Guillain-Barre syndrome and one case of acute post-infectious
      ophthalmoparesis. Such antibodies were found in most cases (8 out of 9) of Miller
      Fisher syndrome, and at very high titres, in one case of Guillain-Barre syndrome
      characterised by an initial ophthalmoparesis, and in the case of isolated post
      infectious ophthalmoparesis. The latter was characterised by a long-lasting
      occurrence of these antibodies. Anti-GQ1b antibodies are specific for an immune
      mediated neuropathy of the cranial, especially oculomotor, nerves.

PMID- 9922820
TI  - Inhibitory effects of mesial temporal partial seizures onto frontal neocortical
      structures.
AB  - PURPOSE: A retrospective evaluation of the ictal temporal tracer uptake and the
      perfusion pattern in other neo- and subcortical structures was performed to
      define typical extratemporal changes of rCBF that might further aid the
      differentiation of temporal and extratemporal seizures. METHOD: Ictal and
      interictal rCBF brain SPECT studies were done in 17 patients with seizures of
      mesial temporal onset according to scalp electroencephalography (EEG) and
      electrocorticography (ECoG) using 99mTc-ECD. Except for hippocampal
      sclerosis/atrophy, which was found in 11/17 patients, no morphologic anomalies
      were detected by MRI. Ictal tracer injections were given immediately after the
      onset of the seizure according to continuous video-EEG monitoring. The injection
      latency was two to twenty seconds. The data acquisition was done 45 minutes after
      the tracer injection using an annular crystal system (Ceraspect, DSI). In 15
      patients a semiquantitative ROI-analysis of the tracer uptake in temporal and
      frontal regions could be obtained. RESULTS: All ictal studies correctly localised
      the affected temporal lobe. A detection of the epileptogenic focus itself was
      successful in 59% of patients while in the remaining patients the maximum of
      tracer uptake was not found to be located in the mesial temporal lobe only. In
      contrast to all other cerebral structures, only within the ipsilateral basal
      frontal cortex a frequent reaction to the temporal seizure was found. The basal
      frontal cortex ipsilateral to the affected temporal lobe showed a reduction of
      tracer uptake between the ictal and interictal study in 82% of patients which was
      semiquantitatively significant using a paired t-test (p < 0.05). Other neo- or
      subcortical structures showed inconsistent results. CONCLUSION: Secondary
      involvement of neocortical temporal structures in ictal rCBF-SPECT with 99mTc-ECD
      occurs early and focal maxima of tracer uptake within the temporal lobe do not
      necessarily represent the epileptogenic focus itself. Seizures of mesial temporal
      origin did not activate but frequently depressed the ipsilateral basal frontal
      tracer uptake during the early ictal phase. This phenomenon may account for some
      aspects of the clinical appearance of mesial temporal seizures.

PMID- 9922821
TI  - Subcutaneous sumatriptan compared with usual acute treatments for migraine:
      clinical and pharmacoeconomic evaluation.
AB  - Cost-effectiveness and cost per successful treatment has been evaluated in 186
      outpatients randomised to treat moderate to severe migraine attacks either with
      subcutaneous sumatriptan 6 mg (n = 97) or with their current therapy (n = 89)
      during an open, multicentre study of 3 months. Within 2 hours, headache severity
      decreased to none/mild in 86% of all attacks in the sumatriptan group (STG)
      compared to 25% in the customary group (CTG). Migraine was alleviated earlier in
      the STG than in the CTG (median 3.78 vs. 13.39 hours, p < 0.0001). The direct and
      total cost of treatment was 133 and 2012 BF, respectively, in the CTG and 1400
      and 2522 BF, respectively, in the STG. Measuring the effectiveness of earlier
      pain relief with sumatriptan, the incremental cost-effective ratios for direct
      and total cost were 132 and 53 BF per hour of relieved pain, respectively. For
      this price, significantly more sumatriptan patients improved their quality of
      life by more than 20% (61.6 vs. 20.6% patients, p < 0.001) and less sumatriptan
      patient consulted a medical professional (11.3 vs. 29.2% patients, p < 0.01),
      used less medication for adverse events (6.2 vs. 22.5%, p < 0.001) and suffered
      less from associated migraine symptoms. The median number of hours of diminished
      work-efficiency (3 vs. 7 hours, p < 0.01) or of suspension of non-professional
      activity (10 vs. 24 hours, p < 0.001) was also significantly lower in the STG.
      The total cost per successfully treated patient was lower in the STG. Sumatriptan
      is more effective, provides a better quality of life, reduces health care
      resource utilisation, and improves work productivity as compared to the CTG,
      thereby resulting in a favourable cost-effectiveness ratio.

PMID- 9922822
TI  - Features of spontaneous improvement in syringomyelia with low-situated cerebellar
      tonsils.
AB  - We analysed four patients who showed spontaneous improvement among the 19
      nonsurgically treated cases of syringomyelia with low-situated cerebellar tonsils
      who visited our outpatient clinic. MR images both before and after improvement
      were available for two of these patients; CT-myelography before improvement and
      MR images after improvement were used for two patients. Consequently, we were
      able to abstract several features from detailed and precise neurological and
      radiological evaluations of these patients. These features consisted of mild
      (rather than severe) disability, as well as three radiological features--a
      rounded shape of the lower edge of the cerebellar tonsils, a low tightness of the
      foramen magnum, an elevation of the tonsils during the course of the disease.
      Results of our radiological analyses were consistent with the theories proposed
      for the pathogenesis of syringomyelia in the light of the CSF flow around the
      foramen magnum. We propose that the features we have isolated are useful in
      determining treatment policies and prognoses of patients with syringomyelia,
      accompanied by low-situated cerebellar tonsils.

PMID- 9922823
TI  - Neurological complications of intravenous immunoglobulin (IVIg) therapy: an
      illustrative case of acute encephalopathy following IVIg therapy and a review of
      the literature.
AB  - We report the case of a 73-year-old man who developed an acute encephalopathy
      during IVIg therapy for AIDP. The signs and symptoms of the encephalopathy
      completely resolved after discontinuation of the treatment. We also reviewed the
      literature over the major neurological complications of IVIg therapy, including
      aseptic meningitis, cerebral infarction, and acute encephalopathy. About 30 cases
      of aseptic meningitis are reported. They are probably related to an
      immunoallergic reaction, caused by the entry of the exogenous IgG into the CSF
      compartment. CSF examinations usually show a neutrophilic or a mixed pleocytosis.
      Three cases of cerebral infarction and 2 patients with acute encephalopathy,
      following IVIg therapy, were also reported in the literature. Cerebral vasospasm,
      cerebral vasculitis, and/or serum hyperviscosity may be implicated in the
      pathogenesis of these neurological complications. There is a clinical similarity
      between these IVIg-related encephalopathy and the "reversible posterior
      leukoencephalopathy syndrome", described by Hinchey et al., 1996.

PMID- 9922824
TI  - Pagetic sarcoma of the calvarium: report of two cases.
AB  - Two cases of calvarium sarcoma with intracranial extension, consecutive to Paget
      disease of the skull are presented. The neurosurgical implications of this rare
      complication of a common disease are reviewed. In both cases, the symptoms of
      malignant degeneration were unspecific and blurred by the presence of a well
      known Paget disease. Increasing headaches, focal neurological deficits and signs
      of intracranial hypertension were observed. Skull X-rays and Computerised
      Tomography did not allow to make the difference between Pagetic bone and sarcoma.
      In the second case, Magnetic Resonance Imaging was the most accurate in
      determining the precise localisation of the tumour, and the subdural invasion.
      Extensive surgical resection was carried out, by craniectomy of the tumoural
      bone, followed by cranioplasty. Dural sinus involvement and tumour
      hypervascularisation caused important peroperative blood loss in both patients.
      In the second case, the tumour invaded the subdural space through a Pacchioni
      granulation. Survival of patients with Pagetic sarcoma seems shorter when
      compared to post-radiation or primitive osteosarcoma, despite adjuvant therapies,
      probably because of late diagnosis and incomplete surgical resection. The mean
      reported survival rate is 6 months. Although the first patient died within 4
      months, in the second case, the authors obtained a more than two year survival
      with aggressive surgery alone. These cases also illustrate the polymorphism of
      sarcomatous degeneration of Pagetic calvarium, the interest of MRI, and the need
      for close surveillance of patients with known Pagets disease of the skull.

PMID- 9922825
TI  - Primary cerebral lymphoma visualised by means of In-111-pentetreotide
      scintigraphy.
AB  - Primary lymphoma of the central nervous system, until recently representing about
      1% of all brain tumours, shows a dramatically increased incidence in the general
      population as well as in high-risk groups (immunocompromised, AIDS), and may rise
      up to 6% in a population of AIDS patients. The clinical presentation is variable
      and cannot reliably be distinguished from other intracerebral tumours. At
      present, CT and MRI are the methods of choice for diagnosing cerebral lymphomas.
      However, their characteristics are not specific. The radiological picture may
      suggest glioma, meningioma, metastatic carcinoma or even a cerebrovascular
      accident. A labelled somatostatin analogue (pentetreotide) has been proposed as a
      new tracer for the imaging of somatostatin receptors, which have been identified
      by immunocytochemical or radioimmunoassay techniques in several organ systems.
      Somatostatin receptors were also identified in surgical biopsy samples from
      patients with Hodgkin and non-Hodgkin lymphoma and extracerebral lymphoma has
      already been visualised in vivo by means of In-111-labelled pentetreotide. While
      CT images of the brain showed a regression of the tumour after radiotherapeutic
      treatment, the scintigraphic images showed persistence of the tumoural tissue,
      corresponding with the clinical evolution and outcome. Furthermore, the absence
      of extra-cerebral lymphoma tissue, seen on the whole body images, was confirmed
      by post-mortem examination. To our knowledge, this is the first report of a
      primary intracerebral lymphoma visualised by means In-111-pentetreotide.

PMID- 9922826
TI  - [Intact ossicular chain cholesteatoma: aspects and results of conservative
      surgery].
AB  - We present a 24 case-study of intact ossicular chain cholesteatomas among 158
      first-look procedures performed between august 93 and april 96 (15%). The
      eradication of the disease was achieved via canal wall up technique without
      disrupting the ossicular chain in 20 cases (84%). Technical procedures are
      described. This new surgical attitude has enabled us to achieve better functional
      results. Second look procedures have not been necessary in all cases and
      occurrence of residuals has not been increased on a 14 months follow up period (2
      cases out of 24 patients: 8%). Therefore, a longer follow up period is necessary
      to validate the results obtained using this recent concept.

PMID- 9922827
TI  - [Bone anchored hearing aid (BAHA): clinical evaluation].
AB  - The bone-anchored hearing aid (BAHA) allows direct bone-conduction through a
      titanium implant. This avoids skin irritation and seems to improve the sound
      quality when compared with a conventional bone hearing aid. Aim of this work was
      to evaluate this new hearing-aid. PATIENTS AND METHODS: 9 patients have been
      operated on between May 1994 and April 1997. Two aural atresia and 7 radical
      mastoidectomy; 6 had prior conventional bone hearing aid and one a bilateral air
      conduction hearing aid. Their mean bone conduction threshold was 28 dB (17-38
      dB). Their maximum speech discrimination score was 100%. Audiological tests and
      questionnaires were used for the evaluation. RESULTS: The mean follow-up was 9
      months (3-35). Osseointegration succeeded in the 9 cases. Skin tolerance was
      excellent in 6 cases. 3 patients had transient adverse skin reactions, with one
      having needed a revision surgery under local anesthesia. All patients use their
      BAHA everyday. The mean prosthesis gain was 36 dB (20-50 dB). Eight patients
      completed the questionnaire. Patients reported an overall satisfaction score
      between 9 and 10 (range 6-10). BAHA advantageously replaced the prior hearing aid
      (mean satisfaction score: 9.1 for BAHA versus 5.9). The only complaints were
      sensitivity to wind noise and lack of a phone connexion.

PMID- 9922828
TI  - [Tongue base reduction with hyoid-epiglottoplasty. A surgical alternative in
      severe sleep apnea syndromes].
AB  - We present preliminary results and indications of tongue base reduction with hyo
      epiglottoplasty for the treatment of severe obstructive sleep apnea syndrome
      (OSAS) due to isolated hyolingual abnormalities. The procedure consists in a
      subtotal resection of the tongue base after identification and derouting of the
      lingual neurovascular bundle. Hypopharyngeal enlargement, epiglottis
      verticalization, floor of the mouth tension and hyoid bone repositioning are also
      performed during the procedure. 14 severe OSAS male patients (mean apnea-hypopnea
      index of 71) were treated in our institution from November 1992 to February 1996.
      Indications were determined after a cephalometric analysis and a magnetic
      resonance imaging evaluation. Results were evaluated on clinical and
      polysomnographic criteria. No neurovascular complications occurred. Clinical
      results were excellent but success rate based on polysomnography was 50%. These
      preliminary results led us to change some of the steps in the technique. We also
      identified a predictive factor of success on the cephalometrics: an oropharyngeal
      area greater than 25 cm2.

PMID- 9922829
TI  - [Clinical, etiologic and therapeutic aspects of chronic sphenoid opacities].
AB  - A series of 23 patients with sphenoid disease were seen between 1992 and 1997.
      The most common symptom was headache. This headache was found to be nonspecific.
      Cranial nerve abnormalities were found in two patients. The different types of
      radiolographic images were analyzed, and compared with the surgical diagnosis.
      Twenty-one patients underwent surgical exploration by intranasal endoscopic
      sphenoidotomy. This approach allowed drainage and inspection of the sinus.

PMID- 9922830
TI  - [En bloc resection of the carotid axis in epidermoid carcinoma of the head and
      neck. Retrospective analysis of 7 cases].
AB  - En bloc resection of carotid artery involved by squamous cell carcinoma was
      performed in 7 patients from 1993 to 1997. Cerebral tolerance was tested with
      qualitative evaluation of cerebral blood flow during preoperative balloon test
      occlusion of the internal carotid artery. Four patients later underwent permanent
      carotid occlusion prior to en bloc resection, 2 patients underwent carotid
      ligation without reconstruction and one patient underwent carotid resection
      associated with carotid reconstruction. The preliminary neurovascular and
      carcinologic results are presented. One patient had definitive stoke
      postoperatively. Follow-up ranged from 3 to 34 months. Two patients died by the
      6th and 26th postoperative month respectively. Among the remaining 5 patients,
      tumoral recurrence occurred in two. Two patients have survived more than 2 years,
      but one of them had local recurrence and distant metastases. Considering these
      data and the review of the literature, selection of patients after carcinologic
      and cerebral tolerance evaluation is important in order to improve survival and
      quality of life of these patients.

PMID- 9922831
TI  - [Value of laser CO2 myringotomy in the treatment of seromucous otitis].
AB  - To date serous otitis media is usually treated by surgical setting of ventilating
      tubes. This technique provides good results on auditory acuity, however,
      complications such as chronic otorrhea, tympanosclerosis and tympanic perforation
      are rather frequently encountered. We present the results of our technique for
      treatment of serous otitis media consisting in a CO2 laser myringotomy. This
      technique was applied in 20 consecutive adult ears. The operatory microscope was
      connected with a co-axial CO2 laser device. The 20 myringotomies performed
      without insertion of ventilating tubes by this technique were all closed after 4
      weeks with an average closing time of 17 days with no complications. In 60% of
      the cases, the serous otitis media was cured after a period of three months. CO2
      laser myringotomy is a valuable alternative technique in the treatment of serous
      otitis media.

PMID- 9922832
TI  - [A new multidirectional sigmoid sinus retractor].
AB  - Retraction of the sigmoid sinus requires a strong instrument. The instruments
      currently available allow only a limited degree of freedom due to their lack of
      mobility and versatility. A new sigmoid sinus retractor (MICRO
      FRANCE/INSTRUMENTARIUM) was constructed to facilitate the surgeon's task by
      offering the following advantages: Three-dimensional mobility of the blade:
      lateral, rotatory and longitudinal, Safe positioning of the retractor by three
      sets of sharp teeth, Fixation of blade by a single screw, Strong retraction
      without giving-way.

PMID- 9922833
TI  - [Parapharyngeal tumors. Apropos of 6 cases].
AB  - We conducted a retrospective study of six patients presenting a parapharyngeal
      tumor and an analysis of data of the literature and recall classification of
      these tumors and their anatomo-clinics characters, therapeutic and diagnostic
      problems highlighting. These tumors are rare and have various origins, their
      treatment is almost always surgical by cervical approach which can be undertaken
      only after a rigorous exploration, systematically associating computed tomography
      scan and magnetic resonance imaging. Transoral resection is strongly advised
      against as it is potentially harmful.

PMID- 9922834
TI  - [Interruption of the lateral sinus in surgery of paraganglioma and acoustic
      neurinoma. Apropos of 2 complications].
AB  - The sigmoid sinus, one of the main structures of the venous cerebral circulation,
      may be interrupted by various pathological or surgical processes. Usually,
      interrupted circulation is compensated by collateral or contralateral venous
      circulation. No neurological deficit is observed. We report two neurological
      complications: cerebellar infarction and intracranial hypertension, secondary to
      lateral sinus interruption during removal of a paraganglioma and an acoustic
      neuroma. Attention is drawn on the importance of preoperative evaluation of the
      venous cerebral circulation to prevent such complications.

PMID- 9922835
TI  - [Atelectasis of the maxillary sinus. Analysis of progression stages. Apropos of 4
      cases].
AB  - We analyzed atelectasic processes occurring in the maxillary sinus. Several
      publications in the literature have tempted to analyze the pathogenesis.
      Clinically the processes are often silent and only revealed when the major
      opthalmological complication, enophthalmia, becomes patent. In other cases there
      is a long history of chronic sinusitis. There is a spectacular retraction of the
      maxillary sinus walls leading to collapse of the orbital floor and enophthalmia.
      We report four cases of maxillary sinusitis with atelectasia of the sinus walls
      at different stages of progression. These observations and data in the literature
      emphasize the importance, whatever the state of development, of endoscopic osteal
      decompression to avoid ophthalmological complications.

PMID- 9922836
TI  - [A case of very late malignant degeneration of pleomorphic adenoma].
AB  - Incomplete excision of a pleomorphic adenoma exposes to a high risk of recurrence
      and tumor spread, making secondary surgery more difficult or a malignant
      transformation with a poor vital prognosis likely. Three histological types of
      pleomorphic adenomas can be observed when the tumor undergoes a transformation,
      namely the carcinoma ex-pleomorphic adenoma, the true malignant mixed tumor and
      the benign metastasizing mixed tumour.

PMID- 9922837
TI  - [Sexual repercussions of prostatic adenoma surgery for the man and his partner.
      Role of retrograde ejaculation].
AB  - Very few patients complain of the sexual repercussions of surgery for benign
      prostatic hyperplasia (one or two per year in a very active Parisian Urology
      department). However, when the patient presents such complaints, they are always
      dramatic and the patient is particularly critical of the surgeon who operated on
      him. In order to more clearly understand the importance of these exceptional
      complaints, associated with marked anxiety, the authors reviewed an IFOP survey
      concerning sexuality in the elderly: at the age when most prostatectomies are
      performed, orgasm is no longer considered to be essential. It is essential to
      always make sure that the patient has clearly understood the explanations given
      to him, which is particularly difficult in foreign patients. Prostatectomy is
      obviously an urological indication, but when it does not constitute an emergency,
      the urologist should defer the operation if his patient still has an active sex
      life (sexual intercourse once a week, for example).

PMID- 9922838
TI  - [The woman and the new methods of treatment of male sexual impotence].
AB  - New treatments for male impotence are now available, mainly sildenafil (oral) and
      prostaglandin 1 (intraurethral). These new treatments, which will be easier to
      use for men, raise problems of acceptability by women. Schematically, women adopt
      certain behaviours in relation to male sexuality, which can be characterized as
      "castrating", "infantile", "not interested", or "narcissistically wounded". New
      treatments, which will certainly be better accepted by patients and their
      partners, must not mask the ubiquitous participation of a psychogenic component
      in all forms of male impotence, including so-called "organic" impotence. The
      management of male impotence can therefore only be conceived in a context of a
      "couple project" after having defined the contribution of medicine and the
      patient's personal investment in finding a solution to his problem. The blind
      prescription and use of a drug wrongly considered to be a "male youth pill" could
      lead to major and probably harmful sociological changes in the context of the
      ever-evolving male-female relationships and in a context of ageing of the
      population.

PMID- 9922839
TI  - [Treatment of stress urinary incontinence in women: rehabilitation or surgery?].
AB  - Considerable progress has been made in the treatment of female urinary
      incontinence over the last 20 years, affecting both surgical treatment, by the
      introduction, apart from reference techniques, of so-called "minimal" techniques,
      which allow an extension of the indications to elderly patients, and medical
      treatment, but also due to the introduction of increasingly better defined
      retraining techniques. A better understanding of the pathophysiology of
      incontinence and the growth of urodynamic techniques allow a better analysis of
      the mechanisms responsible for incontinence, which is often multifactorial. The
      prevalence of female urinary incontinence also gives this disease a considerable
      economic significance. Surgery is therefore no longer currently the only
      treatment that can be proposed to the patient. The respective indications for
      retraining and surgery need to be discussed, bearing in mind that, schematically,
      the 2-year results of surgery achieve 80 to 85% of cure with a more marked
      erosion over time when the initial repair was less solid, and retraining cures
      approximately 30% of women and improves another 30%.

PMID- 9922840
TI  - [Interstitial cystitis].
AB  - Interstitial cystitis is a particular type of cystitis with clear urine,
      essentially observed in women. Persistent painful urinary frequency and bladder
      heaviness are suggestive of the diagnosis. Two different forms have been
      distinguished according to severity: Hunner's ulcer and small capacity bladder;
      bladder distension to 800 ml, followed by haemorrhagic petechiae; with a whole
      series of intermediate forms. The bladder wall undergoes inflammatory
      reorganization, without infection, leading to fibrosis. The disease is improved
      by hydrocortisone instillations. Hunner's ulcer can be treated by partial
      resection. If the cystitis deteriorates, bladder replacement by detubulized
      intestinal graft may be required.

PMID- 9922842
TI  - [Pseudotumorous focal xanthogranulomatous pyelonephritis in children. Apropos of
      a case].
AB  - Xanthogranulomatous pyelonephritis is a particular form of chronic
      pyelonephritis. It is observed less frequently in children and can sometimes
      present with a focal pseudoneoplastic appearance. An 11-year-old child was
      admitted with abdominal pain, alteration of the general state and weight loss
      without fever or palpable mass. Medical imaging was unable to distinguish between
      malignant renal tumour or tuberculosis. The diagnosis was confirmed by the
      inflammatory and purulent appearance of the mass and histopathological
      examination of the biopsy fragment. Percutaneous drainage of the abscess,
      combined with antibiotics provided marked improvement. Despite its rarity and its
      nonspecific clinical features, focal xanthogranulomatous pyelonephritis must be
      considered in order to propose conservative treatment.

PMID- 9922841
TI  - [Therapeutic strategies in urinary tract infections in women].
AB  - Simple acute cystitis is cured by single-dose or 3-day treatment. Complicated
      acute cystitis requires clinical, bacteriological and imaging examinations.
      Treatment must be continued for 10 days and controlled. Acute pyelonephritis in
      women requires bacteriology, ultrasonography and plain x-rays and must be rapidly
      treated by fluoroquinolone or cephalosporin. High-risk acute pyelonephritis
      justifies admission to hospital, more elaborate examinations and active
      treatment.

PMID- 9922844
TI  - [Spontaneous rupture of bladder diverticulum. Apropos of a case].
AB  - We report a case of spontaneous rupture of a bladder diverticulum. A 65-year-old
      man presented with urinary retention and serious infection. At clinical
      examination, the patient had a distended abdomen, tenderness of the left flank
      and left lumbar region and benign prostatic hyperplasia. Urinary catheterisation
      yielded bloody and purulent urine. CT scan showed a paravesical collection
      extending to the left lumbar region. Blood count showed anaemia and leukocytosis.
      Emergency surgical exploration found a large infected bladder diverticulum with
      necrosis and perforation of the wall. Treatment consisted of resection of the
      necrotic tissue and suture of the diverticulum neck. Convalescence was
      uneventful.

PMID- 9922843
TI  - [Bladder paraganglioma (pheochromocytoma): a rare tumor in children. Apropos of a
      case].
AB  - The authors report the first case of bladder paraganglioma in a child admitted to
      their department successfully treated by partial cystectomy. The diagnosis was
      established histologically, after failure of clinical diagnosis. Retrospectively'
      the authors think that preoperative diagnosis should have been possible and
      emphasize the importance of a thorough clinical examination.

PMID- 9922845
TI  - [Urethral diseases in children at surgical departments of the Cotonou Hospital.
      Apropos of 77 cases].
AB  - Over a 6-year period in the surgical departments of Cotonou hospital, urethral
      diseases in children represented 20% of all infantile urological diseases and
      essentially consisted of urethral strictures (26 cases), hypospadias (22 cases),
      posterior urethral valves (12 cases), prolapsed urethral mucosa, the only disease
      observed in girls (9 cases). These diseases generally do not raise any diagnostic
      problems, but the real problem concerns follow-up of these children, who are
      usually lost to follow-up after discharge.

PMID- 9922846
TI  - [Urethral diverticula in women. Apropos of 15 cases].
AB  - Urethral diverticulum is a rare disease, arising in the urethrovaginal septum and
      communicating with the urethra through an orifice. Characterised by clinical
      polymorphism, it is diagnosed by urethrocystography and transvaginal ultrasound.
      We report a series of 15 cases of urethral diverticulum over a 10-year period.
      The mean age of the patients was post-voiding was 36 years (range 24-50). The
      symptoms were recurrent urinary tract infections (66%), post-voiding urethral
      leakage (22%), vaginal pain (22%). Clinical examination found a vaginal mass in
      all patients. Retrograde urethrocystography showed the diverticulum in every
      cases, while IVP confirmed the diagnosis in only 62% of cases. Treatment is
      surgical and consists of removing the diverticulum via a vaginal approach. Short
      and long-term course is favourable. All patients were asymptomatic and the follow
      up urethrocystography showed no diverticular recurrence.

PMID- 9922847
TI  - [Diagnostic value of echocardiography and thoracic spiral CT angiography in the
      diagnosis of acute pulmonary embolism].
AB  - The objective of this study was to define the limits of echocardiography and to
      evaluate thoracic spiral CT angiography (TSCTA) for the diagnosis of pulmonary
      embolism (PE). One hundred twelve consecutive patients, hospitalised for
      suspected PE, were included in this prospective study. All were investigated by
      pulmonary ventilation-perfusion scintigraphy (Sc) and 50 had a high probability
      of PE on this examination. Sc was normal in 22 patients. Forty patients were
      excluded because of an intermediate probability. In 50 patients with PE confirmed
      on Sc, transthoracic echocardiography (TTE) showed only indirect evidence of PE
      (intracavitary thrombus in 4% of cases). TSCTA demonstrated PE in 82% of cases
      and did not show any thrombus image when Sc was normal. Its negative predictive
      value was therefore 70% and its positive predictive value was 100%. Its
      sensitivity varied according to degree of perfusion defect (96% in the case of
      lobar lesion, 66% in the case of segmental lesion and 16% for a subsegmental
      lesion). Multidimensional transoesophageal echocardiography (TOE), performed in
      37 of the 50 patients with PE, only revealed thrombi in the pulmonary tree in 3
      patients (8%), all presenting severe PE. No thrombus was visualized on TOE in
      patients with non-serious PE. All thrombi observed on TOE were also demonstrated
      by TSCTA. In conclusion, TTE usually provides only indirect signs of PE. TOE has
      a poor diagnostic sensitivity for PE. TSCTA has a better sensitivity than TOE for
      the detection of thrombi in the pulmonary artery trunk and proximal centimetres
      of its two branches, but normal CT angiography cannot exclude a distal PE.

PMID- 9922848
TI  - [Predictive indices of the persistence of left ventricular dilatation after valve
      replacement for chronic aortic insufficiency. Echocardiographic study].
AB  - The objective of this study was to define the echocardiographic indices
      predictive of persistence of left ventricular dilatation one year after valve
      replacement for chronic aortic incompetence. Thirty four consecutive patients (32
      men and 2 women, age: 35.6 +/- 10 years) operated for post-rheumatic chronic
      aortic incompetence, were included in this series. All patients were investigated
      by echocardiography less than 15 days before and one, six and twelve months after
      surgery. The parameters studied consisted of measurement of ventricular diameter,
      shortening fraction and ejection fraction as well as aortic incompetence Doppler
      indices (jet-left ventriculr outflow tract diameter, jet-left ventricular outflow
      tract diameter/subaortic diameter ratio, half-pressure time, aortic isthmus end
      diastolic velocity). Preoperative echocardiographic data and the results one year
      after valve replacement were compared for each patient. The left ventricle
      remained more dilated at one year in patients with a preoperative end-diastolic
      diameter > 80 mm, an end-systolic diameter > 55 mm, a shortening fraction < 25%,
      an ejection fraction < 50%, a jet diameter > 16 mm, a jet diameter/subaortic
      diameter ratio > 65% or a half-pressure time < 350 ms. In conclusion; an end
      diastolic diameter > 80 mm, an end-systolic diameter > 55 mm, a shortening
      fraction < 25%, a jet diameter > 16 mm, a jet diameter/subaortic diameter ratio >
      65% and a half-pressure time < 350 ms appear to represent the main predictive
      factors of the persistence of ventricular dilatation one year after aortic valve
      replacement for chronic aortic incompetence.

PMID- 9922849
TI  - [Ultrasonic demonstration of carotid atherosclerosis in black Cameroonian adults
      with cardiovascular risk].
AB  - The objective of this study was to determine the prevalence of carotid
      atherosclerosis in black Cameroonian adults presenting cardiovascular risk
      factors (CVRF). It was based on 77 subjects over the age of 40 years (50 men and
      27 women) with at least one major CVRF, such as hypertension (HT), smoking,
      dyslipidaemia or diabetes mellitus. Obesity [body mass index (BMI), waist/hips
      ratio (W/H)] and hyperuricaemia were also taken into account. Duplex ultrasound
      examination of the carotid arteries was performed with a Siemens apparatus
      equipped with a 7.5 MHz transducer array. An atheromatous plaque was defined as
      medio-intimal thickening > or = 1.5 mm, with either protrusion or
      hyperechogenicity. Risk factors were distributed as follows in our serie: HT:
      82%, Obesity: 49% (W/H) and 32% (BMI); Diabete: 32%; Smoking: 23%;
      Hyperuricaemia: 21%; Hypercholesterolaemia: 13%. 19 subjects (25%) (12 men and 7
      women with a mean age of 63 years) presented one or more atheromatous plaques in
      the carotid arteries. Hyperuricaemia and hypercholesterolaemia were significantly
      correlated with the presence of plaques, with a marked tendency in subjects over
      the age of 70. In this study, hyperuricaemia and advanced age appeared to be
      independent arterial risk factors on multivariate analysis. In conclusion, our
      data show that carotid atherosclerosis does exist in our populations, especially
      in elderly subjects with cardiovascular risk factors. The particular role of
      hyperuricaemia as a predictive factor of atheromatous plaques in black
      Cameroonian subjects needs to be defined.

PMID- 9922850
TI  - [Incidental discovery of asymptomatic Loeffler fibroplastic endocarditis. Report
      of a case].
AB  - The authors report a case of fibroplastic endocarditis discovered during
      echocardiography in an asymptomatic patient in the context of assessment of
      systematized electrocardiographic modifications. The diagnosis, strongly
      suspected on the basis of the cardiac MRI findings, was finally confirmed by
      endocardial biopsy.

PMID- 9922851
TI  - [Ostial stenosis of the common trunk of the left coronary artery 20 years after
      mediastinal irradiation].
AB  - A 43-year-old woman with no risk factors received mediastinal radiotherapy of 35
      Grays at the age of 23 years for Hodgkin's disease, followed by cure of the
      neoplastic disease. Twenty years later, following a threatened infarction
      syndrome, coronary angiography revealed ostial stenosis of the left coronary
      trunk. The course was rapidly unfavourable immediately following the examination.

PMID- 9922852
TI  - [Infectious endocarditis, did it change?].
AB  - Although the incidence and prognosis of infectious endocarditis have remained
      relatively stable for many years, this disease has recently undergone major
      modifications of its aetiological and bacteriological profiles, and has benefited
      from progress in echocardiographic techniques. New diagnostic criteria have been
      proposed and considerable therapeutic progress has been accomplished, in both
      medical (antibiotic therapy) and surgical (conservative surgery, homografts)
      modalities.

PMID- 9922853
TI  - [If stent is indicated, which one should be chosen?].
AB  - Coronary stenting is justified by the prevention of acute angioplasty accidents
      (more or less occlusive, extensive dissection) and by their clearly established
      value in particular cases (chronic occlusion, venous graft, elastic recoil).
      Other clinical situations, such as prevention of restenosis are not absolute
      indications for first-line stenting and some techniques assessing the coronary
      functional appearance (Doppler, pressure) could select candidate patients for
      stenting. The choice of stent depends on the type of coronary lesion and each
      team's experience, bearing in mind that the ideal stent, which does not exist,
      should combine radial force, softness, good visibility, preservation of
      collateral vessels, and must be atraumatic and inexpensive. Finally, when the
      remodelling component of restenosis has been eliminated by stenting, the next
      step will be to limit or even prevent intrastent intimal hyperplasia by
      attractive techniques, which still need to be evaluated (intracoronary
      radiotherapy, gene therapy, etc.).

PMID- 9922854
TI  - [Detection of myocardial viability by stress echocardiography].
AB  - Dobutamine echocardiography has gradually acquired a place among the currently
      available techniques to evaluate myocardial viability. It is a very efficient
      technique, easily accessible and inexpensive. It detects preservation of the
      myocyte contractile apparatus, which unlike other tests best assesses myocardial
      viability. Its value in stunned and hibernating myocardium is herein described.

PMID- 9922855
TI  - [Place of beta blockaders in the treatment of heart failure].

PMID- 9922856
TI  - [Study of the general and topical tolerance of Trinipatch and its clinical
      efficacy in the therapy of chronic stable angina in 5078 coronary disease
      patients].
AB  - Nitrates still play an important role in the treatment of coronary heart disease
      after more than hundred years of use in this indication. Following oral
      administration, they undergo intense gastric hydrolysis, and are largery
      destroyed by the first-pass effect. The development of an attenuation phenomenon
      of the therapeutic effect has been frequently reported during continuous
      treatments at fixed doses. Percutaneous administration of nitroglycerin due to
      the development of transdermal devices palliates these various obstacles.
      Trinipatch is a small, transparent, matricial, monolayer patch with an absorption
      promoter, marketed in two dose-strengths (5 mg/24 h and 10 mg/24 h) by
      Laboratoires Synthelabo. Its systemic and local safety and clinical efficacy were
      studied by 383 private cardiologists and 2,294 general practitioners in 5,079
      coronary patients, between the ages of 19 and 91 years, in two open, multicentre
      trials lasting 3 months. The systemic safety, assessed by adverse event
      reporting, was good. 2.7% of patients experienced adverse events, but only 0.3%
      of patients presented a serious adverse event. The effects most frequently
      encountered were vasodilator effects. A very good stability of cardiovascular
      parameters was observed, with no reflex tachycardia. The local safety, evaluated
      by the Draize scale, was also satisfactory; after 1 month and 3 months of
      treatment, 6.6% and 5.7% of patients presented erythema, usually isolated and
      moderate. The clinical efficacy was evaluated by subjective criteria in the 740
      patients included by cardiologists. A significant reduction of the number of
      angina attacks and the numbers of doses of nitroglycerin was observed. The
      percentage of pain-free patients increased from 18.2% at the start of the study
      to 76% at the end of the trial. These two trials confirmed the good systemic and
      local safety and clinical efficacy of Trinipatch.

PMID- 9922857
TI  - [Picture of the month. Hydatid cyst of cardiac localization].

PMID- 9922858
TI  - [In vitro resistance of Propionibacterium acnes and Staphylococcus epidermidis to
      antibiotics: should our antibiotic prescription practices for the treatment of
      acne be changed?].

PMID- 9922859
TI  - [How should leprosy be treated?].

PMID- 9922860
TI  - [The resistance of Propionibacterium acnes and Staphylococcus epidermidis to
      cyclines. The Research and Study Group on Acne].
AB  - BACKGROUND: A rising percentage of tetracycline-resistant Propionibacterium acnes
      strains has been reported in the English literature. PATIENTS AND METHODS: We
      studied a population of 16 patients with acne who had been treated with oral
      tetracyclines during the preceding year. A bacteriological examination of a skin
      biopsy was obtained in all patients to determine aerobic and anaerobic flora as
      wells as resistance to tetracycline and minocycline. RESULTS: Staphylococcus
      epidermidis strains were frequently resistant to tetracycline (87.5%) as well as
      minocycline (30%). Tetracycline-resistant Propionibacterium acnes were also
      observed (7%). Inversely, we were unable to evidence any minocycline-resistant
      Propionibacterium acnes strains. CONCLUSION: These findings emphasize the
      importance of determining whether therapeutic response is related or not to the
      presence of resistant strains.

PMID- 9922861
TI  - [Leprosy disclosed by polyarthritis].
AB  - BACKGROUND: We report a case of leprosy observed in a French woman who had lived
      in Africa 30 years earlier. The clinical presentation was misleading, suggesting
      connective tissue disease. CASE REPORT: A 69-year-old woman was hospitalized in
      April 1996 for inflammatory joint disease. The first manifestations had developed
      three years earlier and the patient had been on systemic corticosteroid therapy
      associated with anti-malarials since 1993. The clinical presentation
      progressively included neurological and skin manifestations. Histology
      examination gave the diagnosis of lepromatous leprosy. Three-drug anti-leprosy
      treatment in one oral dose was initiated. DISCUSSION: Chronic Mycobacterium
      leprae infection usually leads to overt leprosy with neurological and cutaneous
      involvement. Rheumatological forms are less common and found almost exclusively
      during leprous reactions. The association of inflammatory join pain with
      neurological and skin manifestations wrongly suggested vasculitis. In addition,
      the general corticosteroid therapy certainly was implicated in disease activation
      and progression to a purely lepromatous form.

PMID- 9922862
TI  - [Pilar dysplasia: an early marker of giant axonal neuropathy].
AB  - BACKGROUND: Giant axonal neuropathy is an autosomal recessive condition
      characterized by progressive degeneration of the central and peripheral nervous
      system. Sensoromotor neuropathy develops around 3 years of age. Children have
      particular faces with curly hair. Characteristic pilar anomalies occur early and
      have diagnostic value. CARE REPORT: An Algerian boy born to consanguineous
      parents (first cousins) had language retardation and gait disorders developed
      around 3 years of age. At 9 years, the child was in a cachetic state with valgus
      feet, amyotrophy and diminished muscle force predominating distally, ataxia,
      areflexia, sensoromotor neuropathy and nystagmus. Skin tropism was altered with
      pale, thin and dry skin, cold, cyanotic limbs and thick curly hair.
      Electrophysiology explorations showed signs of chronic sensoromotor
      polyneuropathy with axonal predominance. Brain and spinal MRI revealed cerebellar
      atropy and signs of leukodystrophy. The spinal tap was normal. A neuromuscular
      biopsy confirmed the diagnosis of giant axonal neuropathy. At examination the
      hair was thick with reduced refrangibility and a pseudo-pili torti aspect.
      DISCUSSION: Giant axonal neurpathy is characterized by anomalous organization of
      the cytoskeleton of intermediary filaments in different types of cells. Hair
      anomalies occur early, before onset of neurological signs. At gross examination
      the hair is thick and curly, sometimes crimped and pale. Examination of the pilar
      shaft shows trichorrhexis nodosa, scalloped fringes and lack of internal
      structure. On the molecular level, there is a reduction in the number of bisulfur
      bridges which could be the cause of defective keratin filament alignement.
      Pathogenicaly, the pilar anomalies are considered as a direct manifestation of
      defective keratin organization characteristic of the disease.

PMID- 9922863
TI  - [Cutaneous vasculitis disclosing cat-scratch disease].
AB  - BACKGROUND: We describe a case of cat-scratch disease ingnaugurated by vascular
      purpura and discuss the role of the causal agent, Bartonella henselae. CASE
      REPORT: A 49-year-old woman presented vascular purpura without fever. Skin biopsy
      demonstrated leukocytoclasic vasculitis. She owned a cat and a had a scratch scar
      on the back of her left hand. A few days later, two inflammatory epitrochlear
      lymph nodes suppurated. Catscratch disease was confirmed by serology and PRC
      analysis of pus aspirated from the nodes. The purpura resolved spontaneously in
      three weeks. Left axillary adenopathy developed and suppurated. In spite of four
      antibiotics, the nodes subsided only ten months later, leaving scars. DISCUSSION:
      Two arguments favor Bartonella henselae as the causal agent in this cutaneous
      vasculitis. The simultaneous onset of the two diseases and the absence of another
      cause of vasculitis. This patient did not have Bartonella henselae endocarditis
      which could have explained this vasculitis. Only one case of hypersensitivity
      vasculitis has been described during cat-scratch disease. The exceptional feature
      of this association is perhaps the result of the unawareness of moderate or
      asymptomatic cat-scratch disease. Bartonella henselae was possibility caused
      hypersensitivity vasculitis.

PMID- 9922864
TI  - [Focal familial palmoplantar keratoderma with punctate hyperkeratosis of the
      palmar creases].
AB  - BACKGROUND: Keratosis punctata of the palmar creases is a variant of punctata
      palmoplantar keratoderma. CASE REPORT: Keratosis punctata of the palmar creases
      was observed in a 53 year-old North African male. The lesions presented as small
      keratotic papules confined exclusively to the flexion creases of the palms and
      digits, with a bilateral localization on the soles. The lesions were sensitive to
      pressure. The proband's 19 year-old son had similar lesions. DISCUSSION:
      Keratosis punctata of the palmar creases is characterized by the development of
      small round keratotic papules, electively and exclusively found in the palmar,
      digital, and uncommonly soles creases. The etiology is unknown. The frequency is
      higher in the black population. Although considered as an hereditary palmoplantar
      keratoderma with autosomal dominant transmission, familial cases with
      localizations on the soles is uncommon.

PMID- 9922865
TI  - [Group A beta-hemolytic Streptococcus: an unusual etiology of perianal dermatitis
      in an adult?].
AB  - BACKGROUND: Perianal dermatitis usually occurs in children between 1 and 8 years
      of age. We report a sixth case in an adult. CASE REPORT: A 33 year-old woman
      complained of perianal itching which quickly extended to the vulva and persisted
      in spite of anti-hemorrhoid and anti-fungal treatments. After 12 days, she had
      painful defecation, a well demarcated perianal and vulvar erythema and anal
      collection. Culture from a perianal swab isolated group A beta-hemolytic
      Streptococcus (ABHS). After surgical treatment of the collection and a 7 days
      oral amoxicillin regimen, the patient recovered with no recurrence. DISCUSSION:
      Symptoms of perianal dermatitis are unspecific, leading to delayed diagnosis and
      underestimated frequency. Symptoms consist in perianal erythema. Swab culture
      shows ABHS. The mechanism of colonization of perianal area is not well defined.
      Although treatment with oral penicillin is usually effective, failures and
      relapses have also been reported. Complications such as deep infection or abcess
      formation are infrequent. A bacterial swab should be made in patients with
      persisting perianal erythma.

PMID- 9922866
TI  - [Childhood plaque milia of the inner canthus].
AB  - BACKGROUND: Milia en plaque is an uncommon skin condition usually seen in adult
      women, typically in the retroauricular region. We report a new localization in a
      young child. CASE REPORT: A 6-year-old girl with an uneventful history had
      developed over the last 7 months an erythematous plaque with numerous whitish
      yellow microcysts on the left internal canthus. No local or general favoring
      factor was found. Skin biopsy showed numerous cystic cavities with an epidermal
      lining containing layers of keratin within a moderately inflammatory
      infiltration. The lesion resolved after enucleation of the cysts and no
      recurrence has been observed after 9 months follow-up. DISCUSSION: Milia en
      plaque is a charateristic erythematous lesion covered with cysts. The usual
      localization is the retroauricular region, but other localizations have been
      reported, mainly on the head. This is the first report involving the internal
      canthus and also in such a young child. One case of a 15-year-old boy has been
      discribed. Milia en plaque is often a primary condition as in our case although
      local or general factors may rarely be inductive. Our case illustrates the
      different localizations possible for milia en plaque, with predominance on the
      head, and the possibility of childhood cases. We prefer the term milia en plaque
      rather than retroauricular milia en plaque.

PMID- 9922867
TI  - [Multiple cutaneous cylindromas associated with parotid and submandibular gland
      cylindromas].
AB  - BACKGROUND: Multiple cutaneous cylindromas are uncommonly associated with
      extracutaneous cylindromas. An association between cutaneous cylindromas and
      salivary gland cylindromas would probably not be fortuitous. CASE REPORT: A 66
      year-old man developed multiple cutaneous cylindromas and cylindromas situated in
      the parotid and submaxillary gland. Histology was similar for both localizations.
      DISCUSSION: This association was probably not fortuitous as the histology was
      similar, other cases have been reported in the literature, and recent complaint
      concerned the development of multiple cutaneous cylindromas and salivary gland
      cylindromas. Salivary gland cylindromas should be searched for in patients who
      develop cutaneous cylindromas as they are more aggressive in nature.

PMID- 9922868
TI  - [Granulomatous mycosis fungoides histologically simulating cutaneous
      sarcoidosis].
AB  - BACKGROUND: Granulomatous mycosis fungoides is an uncommon mycosis fungoides. We
      report a misleading case initially thought to be cutaneous sarcoidosis. CASE
      REPORT: A 34-year-old man developed stationary erythematous plaques on the trunk
      and members. Pathology reported a sarcoidal aspect. No extracutaneous sarcoidal
      lesions were found. The lesions resolved with puvatherapy. Five years later, the
      patient developed a voluminous skin tumor in the scapular area. Pathology
      reported granulomatous mycosis fungoides. Radiotherapy was given. Other plaques
      developed on the skin with the same histological aspect as initially and
      disappeared after local applications of chlormethine. During the clinical course,
      the patient developed visceral localizations of mycosis fungoides in the abdomen
      and pelvic nodes which responded to polychemotherapy. DISCUSSION: Histologically,
      granulomatous mycosis fungoides is defined as the association of epidermotropic T
      cell lymphoma with epitheloid and giant cell dermal granulomas and no necrosis.
      Variants may be misleading when the epitheloid and giant cell aspect
      predominates, as in our observation. An analysis of 28 reported cases showed no
      disinction between the clinical features. Clinical course or treatment for
      granulomatous fungoides mycosis or classical fungoid mycosis. Extracutaneous
      sarcoidosis is rarely associated. Most likely, there is a tissue reaction to the
      lymphona.

PMID- 9922869
TI  - [Simple skin tests in the initial evaluation of the tolerance of a topical
      medication or cosmetic].

PMID- 9922870
TI  - [A new diaper rash in infants?].

PMID- 9922871
TI  - [Case for diagnosis. Scurvy].

PMID- 9922872
TI  - [Case for diagnosis. Multiple trichoepitheliomas].

PMID- 9922873
TI  - [Type I Ehlers-Danlos syndrome].

PMID- 9922874
TI  - [Cutaneous complications of inhaled corticoids].

PMID- 9922875
TI  - [Antisepsis in children].

PMID- 9922876
TI  - [Infectious cutaneous pathology after organ transplantation].

PMID- 9922877
TI  - [Knockout mice: advantages and limitations for biological modeling. Definitions,
      principles and examples].

PMID- 9922878
TI  - [23 December 1886: founding of the medical library of the Saint-Louis Hospital].

PMID- 9922879
TI  - [The biology of epidermal stem cells].

PMID- 9922880
TI  - [Corneal cicatrization].

PMID- 9922881
TI  - [Pilar growth: VEGF and fibroblasts of the follicular papilla].

PMID- 9922882
TI  - [Phospholipase B in the guinea pig: a membrane glycoprotein expressed in the
      intestine and the epididymis].

PMID- 9922883
TI  - [Characterization of phospholipase A2 of human skin involved in the control of
      barrier functions].

PMID- 9922884
TI  - [The cornified envelope, corneo-desmosomes and inter-corneocyte cohesion].

PMID- 9922885
TI  - [The effect of estrogens on the permeability of the bronchial mucosa].

PMID- 9922886
TI  - [Monoamine oxidases in the epithelial cells of the proximal tubules: impact on
      kidney function].

PMID- 9922887
TI  - [Dilemmas in cicatrization].

PMID- 9922888
TI  - [Laser Doppler spectral analysis of patients with Raynaud's phenomenon during a
      standardized thermal test].

PMID- 9922889
TI  - [Nitric oxide: protector of the paranasal sinuses?].

PMID- 9922890
TI  - [The role of skin substitutes in the treatment of diabetic ulcer].

PMID- 9922891
TI  - [Cytotoxic T-cell immune response against melanoma antigens].

PMID- 9922892
TI  - [X-linked ichthyosis: development of a new cellular and metabolic model of
      cholesterol sulfate].

PMID- 9922893
TI  - Youth soccer: an epidemiologic perspective.
AB  - The youth soccer movement in the United States is developing at a tremendous
      rate. This article explores the epidemiology of youth soccer including trends in
      participation, injury data, and injury categories that are of specific concern to
      the young athlete. Finally, recommendations are made regarding possible future
      areas of study and research on youth soccer.

PMID- 9922894
TI  - The female athlete triad.
AB  - The opportunities for girls and women to play soccer has rapidly grown and gained
      acceptance in recent years. The benefits of involvement in soccer, both
      physically and psychologically, are overwhelmingly positive. Despite the
      benefits, girls and women involved in soccer are also at risk for medical
      problems as a result of their sports participation. Amenorrhea, disordered
      eating, and premature osteoporosis are entities known together as The Female
      Athlete Triad. The triad occurs in all sports and is associated with significant
      short- and long-term health consequences, and thus remains a concern for all
      involved in the care of the soccer athlete.

PMID- 9922895
TI  - Optimal preparation for the World Cup in soccer.
AB  - In preparing for the World Cup in soccer, the players should recover in the first
      period after their club season. It is, however, important that they try to
      maintain their endurance capacity by frequently performing aerobic low-intensity
      exercise in order to be prepared for the rebuilding period starting about 5 weeks
      before the World Cup. During the rebuilding period, mainly aerobic high-intensity
      exercise, but also various types of anaerobic training, should be performed. At
      the onset of the tournament, the amount of fitness training can be reduced for
      the players who regularly play on the team; however, frequent sessions with
      aerobic high-intensity training are recommended. The training plan should take
      into account the need of each individual player. Players who do not regularly
      play on the team should follow an extensive fitness training program throughout
      all periods.

PMID- 9922896
TI  - The biomechanics of kicking in soccer.
AB  - This article discusses the basics of kicking skill from development stages
      through mechanical characteristics of upper level players. Specific areas that
      are addressed include developmental levels, kicking components, approach angle,
      forces on the support foot, loading of the swing limb and subsequent movement
      toward ball contact, and the mechanics of ball contact and follow-through.

PMID- 9922897
TI  - Fluid and electrolyte replacement in soccer.
AB  - Soccer can be played under a wide range of environmental conditions.
      Traditionally, fluid replacement is limited during the game, but in reality,
      there are numerous opportunities for fluid ingestion during a match. Many of the
      recommendations on fluid replenishment have been directed at continuous exercise,
      and application of those suggestions can be applied to an intermittent sport like
      soccer.

PMID- 9922898
TI  - Medical issues associated with international competition. Guidelines for the
      traveling physician.
AB  - This article describes the concerns and duties of the team physician while
      traveling for international competition. The medical preparedness and social
      interaction required of the team physician are addressed.

PMID- 9922899
TI  - How can injuries be prevented in the World Cup soccer athlete?
AB  - In order to prevent soccer injuries, different risk factors have to be identified
      as intrinsic (e.g., joint stability or muscle imbalance) and extrinsic (e.g.,
      equipment, turf, and rules risk factors). Some preventive measures are discussed
      in this article, such as shin guards, prophylactic braces and taping (or both),
      and proprioceptive training.

PMID- 9922900
TI  - Leg injuries and shin guards.
AB  - Soccer players have a high risk of soft-tissue injuries to their legs. Fractures
      of the tibia and fibula represent a serious potential injury; despite this, the
      incidence of these fractures in soccer players is unknown. Shin guards have
      become the only protective devices that are required by international and
      collegiate soccer associations. Nonetheless, the protective ability of shin
      guards has only been studied to a limited extent. Shin guards are assumed to be
      most effective at reducing leg abrasions and contusions. The role of shin guards
      in protecting against fractures has yet to be determined. Further analysis of the
      clinical effectiveness and biomechanical properties of shin guards is necessary
      to reduce the rate of leg fractures.

PMID- 9922901
TI  - Mechanisms of injury of the anterior cruciate ligament in soccer players.
AB  - Despite the great amount of research that has been focused on the anterior
      cruciate ligament in recent years, relatively little is known about the exact
      mechanisms that cause these injuries. By defining the factors that contribute to
      these injury mechanisms in soccer players, the authors hope to facilitate
      appropriate training methods and work at preventing these serious injuries.

PMID- 9922902
TI  - Groin pain in the soccer athlete: fact, fiction, and treatment.
AB  - Groin pain in the soccer athlete is a common problem accounting for 5% of soccer
      injuries. Groin distribution has proved to be the most common cause of groin
      pain. Other causes are direct trauma, ostetis pubis, muscle injuries, fractures,
      bursitis, hip problems, and hernia and referred pain. Soccer players with groin
      pain present a complex management problem that is discussed.

PMID- 9922903
TI  - Are brain injuries a significant problem in soccer?
AB  - This article examines the types of forces that the brain is subjected to in
      soccer, secondary to both acute brain injury and repetitive heading of the ball.
      The incidence of acute brain injury is reviewed, as well as studies documenting
      the effects of heading the ball. Finally, 10 actions are proposed that would make
      soccer a safer sport with respect to brain injuries and provide avenues for
      further study in this area.

PMID- 9922904
TI  - Muscle injuries associated with soccer.
AB  - Skeletal muscle has a high potential for regeneration and healing. After injuries
      to this tissue the treatment should focus on the limitation of the injury and
      optimization of the inherent regeneration capacity. This article discusses the
      prevalence of muscle injuries in soccer including diagnoses and complications,
      data from basic science, and therapeutic possibilities.

PMID- 9922905
TI  - Are there long-term sequelae from soccer?
AB  - A long-term soccer career seems to increase the risk for early development of
      osteoarthritis in the lower extremity. Soccer constitutes a risk for
      osteoarthritis in two different ways. First, by the increased risk for knee
      injuries in soccer, such as meniscus and anterior cruciate ligament injuries; and
      second, by the high loading on hip and knee joints that occurs in soccer. The
      risk for these undesirable effects of soccer are higher in top-level players.

PMID- 9922906
TI  - Hypogonadotropic hypogonadism.
AB  - This article outlines the changing pattern of gonadotropin-releasing hormone
      (GnRH)-induced gonadotropin secretion across sexual development, a knowledge of
      which is critical to understanding GnRH secretion in pathologic states such as
      hypogonadotropic hypogonadism. The clinical presentation, differential diagnosis,
      and treatment of hypogonadotropic hypogonadism in humans are discussed.
      Particular emphasis is placed on the contribution of frequent sampling studies of
      gonadotropin secretion and genetic studies to understanding the pathophysiology
      and clinical heterogeneity of isolated GnRH deficiency in humans.

PMID- 9922907
TI  - Male fertility disorders.
AB  - Effective treatments for extreme oligozoospermia include in vitro fertilization,
      recovery of sperm through epididymal sperm aspiration or testicular sperm
      aspiration, and direct injection of sperm through intracytoplasmic sperm
      injection. The clinical evaluation of and treatment options for male patients
      with fertility disorders are detailed in this article.

PMID- 9922908
TI  - The genetic basis of male infertility.
AB  - Defective spermatogenesis can be the end result of a multitude of causes, such as
      systemic disease, malnutrition, endocrinologic disorder, genetic defects,
      anatomic obstruction of the passage of spermatozoa, infections, and environmental
      toxins. A genetic basis of infertility is thought to exist in a majority of
      infertile men currently classified as having idiopathic infertility. Despite
      advances in molecular technology, the pathophysiology of spermatogenic failure in
      a majority of infertile men remains unknown. Although a large number of genes and
      loci in experimental animals are associated with sterility, the human homologues
      of most of these genes have not been cloned yet. Infertility is a heterogeneous
      syndrome in men; therefore, it is likely that a multitude of genes and loci will
      be implicated in different infertility subsets.

PMID- 9922909
TI  - Declining male fertility and environmental factors.
AB  - Male reproductive function has recently attracted increasing attention due to
      reports on time-related decline in semen quality. Analysis of retrospective data
      indicates that sperm counts may have declined in some parts of the world, but
      there seem to be regional differences both in the quality of semen and regarding
      the secular trend. Whereas data on sperm counts may be somewhat difficult to
      interpret, there is no doubt that incidence of testicular cancer has increased
      worldwide. In occupational studies, only a few types of exposures were shown to
      have an impact on male reproductive function; lifestyle and general environmental
      factors may play a more important role. Prospective studies on secular and
      geographic trends in male reproductive function are warranted.

PMID- 9922910
TI  - Reproductive effects of nontesticular illness.
AB  - Diseases in other organs may impair the male reproductive system. Acute critical
      conditions such as severe trauma, surgery, myocardial infarction, burns, liver
      failure, intoxication, or starvation are associated with suppression of
      gonadotropin secretion and secondary hypogonadism. With chronic illnesses, a
      primary testicular disorder with elevated gonadotropin levels may occur. This may
      be associated with increased peripheral conversion of androgens to estrogens,
      resulting in clinical presentation of combined androgen deficiency and estrogen
      excess. The association of hypogonadism and feminization with cirrhosis of the
      liver is a classic example. Types of hypogonadism that may occur with chronic
      anemia, chronic renal failure, chronic spinal cord injury, thyroid diseases,
      Cushing's syndrome, diabetes mellitus, obesity, HIV infection, neoplasia, and
      other chronic illnesses are also described. Numerous drugs have side effects on
      the reproductive system.

PMID- 9922911
TI  - Female infertility.
AB  - This article has provided outcome-based evidence using easily understood graphic
      representation of cumulative pregnancy rates whenever possible for the methods
      used to investigate and treat female infertility. A scheme of basic routine
      investigations in specialist practice is developed and clear guidance provided on
      the choice of treatment for each couple.

PMID- 9922912
TI  - Polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is a syndrome and not a disease. It reflects multiple
      potential etiologies and variable clinical presentations that are reviewed in
      this article. In addition to menstrual dysfunction and hyperandrogenism, women
      with polycystic ovary syndrome also may have hypothalamic-pituitary
      abnormalities, polycystic ovaries on pelvic ultrasonography, infertility,
      obesity, and insulin resistance. A familial pattern occurs in some cases,
      suggesting a genetic component to the disorder. The three major pathophysiologic
      hypotheses that have been proposed to explain the clinical findings of the
      disorder as well as treatment options are reviewed in this article.

PMID- 9922913
TI  - Short- and long-term effects of ovulation induction.
AB  - Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin
      releasing hormone is reviewed. The short- and long-term consequences of these
      therapies are discussed in detail.

PMID- 9922914
TI  - Effects of lifestyle and body composition on the ovary.
AB  - Reduction of metabolic fuel availability below the critical level by food
      restriction or increased expenditure is appropriately accompanied by activations
      of multiple neuroendocrine-metabolic changes resulting in anovulation and
      amenorrhea, an important device for endogenous hypothalamic contraception. This
      reproductive strategy in women is required because of the enormous nutritional
      demand for reproductive success.

PMID- 9922915
TI  - Gonadal damage from chemotherapy and radiotherapy.
AB  - Treatment with cytotoxic chemotherapy and radiotherapy is associated with
      significant gonadal damage in men and women. Alkylating agents such as
      cyclophosphamide and procarbazine are the most common agents implicated. The vast
      majority of men receiving procarbazine-containing regimens for the treatment of
      lymphomas become permanently infertile. Cisplatin-based chemotherapy for
      testicular cancer results in temporary azoospermia in most men, with a recovery
      of spermatogenesis in about 50% after 2 years and in 80% after 5 years. There is
      also evidence of Leydig cell impairment in a proportion of these men, although
      the clinical significance of this is not clear. The germinal epithelium is very
      sensitive to radiation-induced damage, with changes to spermatogonia occurring
      following as little as 0.1 Gy and permanent infertility after fractionated doses
      of 2 Gy and above. Cytotoxic-induced premature ovarian failure is age- and drug
      dependent and ensues in approximately half of women treated with procarbazine
      containing chemotherapy for lymphomas. High-dose chemotherapy, total body
      irradiation, and irradiation at an ovarian dose above 6 Gy usually result in
      permanent ovarian failure. The course of ovarian function after chemotherapy is
      variable, and late recovery occurs in some patients. Several methods of
      preserving gonadal function during potentially sterilizing treatment have been
      considered. Currently, sperm banking remains the only proven method in men,
      although hormonal manipulation to enhance the recovery of spermatogenesis and
      cryopreservation of testicular germ cells are possibilities for the future.
      Transposition of the ovaries to allow better shielding during radiotherapy is of
      use in some women, and the prospect of cryopreservation and reimplantation of
      ovarian tissue is promising.

PMID- 9922916
TI  - Disorders of sexual differentiation.
AB  - An infant born with ambiguous genitalia requires an accurate and prompt diagnosis
      so that a management plan can be formulated. This article discusses the signaling
      cascade of genes that controls sexual differentiation. Clinical disorders
      involving sex reversal or ambiguous genitalia are discussed in relation to the
      genes regulating sexual development. An approach to the treatment of these
      disorders is outlined.

PMID- 9922917
TI  - Male hormone replacement therapy including "andropause".
AB  - Adult onset male hypogonadism and the testosterone deficiency of the aging male
      often are under-recognized entities. The etiologies, presentation, and diagnosis
      of hypogonadism and andropause in the adult male are presented. The expected
      therapeutic goals, potential treatment risks, and management of androgen
      replacement therapy for the adult man are reviewed. The advantages and
      disadvantages of the various androgen delivery systems currently available and
      under investigation are discussed.

PMID- 9922918
TI  - Premature ovarian failure.
AB  - In 1% of women, premature ovarian failure develops by 40 years of age, a
      condition causing amenorrhea, infertility, sex steroid deficiency, and elevated
      gonadotropins. Early loss of ovarian function has significant psychosocial
      sequelae and major health implications. These young women have a nearly two-fold
      age-specific increase in mortality rate. Among women with spontaneous premature
      ovarian failure who have a normal karyotype, half have ovarian follicles
      remaining in the ovary that function intermittently. Indeed, pregnancies have
      occurred after the diagnosis of premature ovarian failure. Thus, premature
      ovarian failure should not be considered as a premature menopause. Young women
      with this disorder have a 5% to 10% chance for spontaneous pregnancy. Attempts at
      ovulation induction using various regimens fail to induce ovulation rates greater
      than those seen in untreated patients; however, oocyte donation for women
      desiring fertility is an option. Young women with premature ovarian failure need
      a thorough assessment, sex steroid replacement, and long-term surveillance to
      monitor therapy. Estrogen-progestin replacement therapy should be instituted as
      soon as the diagnosis is made. Androgen replacement should also be considered for
      women with low libido, persistent fatigue, and poor well-being despite taking
      adequate estrogen replacement. Women with premature ovarian failure should be
      followed up for the presence of associated autoimmune endocrine disorders such as
      hypothyroidism, adrenal insufficiency, and diabetes mellitus.

PMID- 9922919
TI  - [Anxiety and somatoform disorders. Their diagnosis, epidemiology, biological
      causes and therapy].

PMID- 9922920
TI  - [Opipramol in comparison to other drugs--new pharmacologic data].

PMID- 9922921
TI  - [Pharmacokinetics and relative bioavailability of opipramol in the new INSIDON-
      sustained release preparation].

PMID- 9922922
TI  - [Opipramol in behavioral pharmacologic anxiety and depression models].

PMID- 9922923
TI  - [Opipramol in anxiety and somatoform disorders. Results of a controlled study].

PMID- 9922924
TI  - [Opipramol (Insidon) in the treatment of somatoform disorders].

PMID- 9922925
TI  - [Subjective experiences of patients with acute neuroleptic-induced akathisia].
AB  - Neuroleptic-induced akathisia is a clinically important neuropsychiatric syndrome
      with mainly subjectively experienced psychic symptoms on the one hand and well
      observable motor signs on the other. There is no general consensus of opinion on
      the relative importance of these two aspects for diagnosing akathisia. Hence,
      differential diagnosis is difficult and in the absence of a biological marker it
      depends crucially on clinical judgement. Systematic investigation of 27 in
      patients via a semistructural interview, a self-assessment scale (20 in-patients)
      and established akathisia rating scales (Hillside, Barnes, Prince Henry Hospital
      and Chouinard) revealed four characteristics of subjective experience in acute
      neuroleptic-induced akathisia: 1. perception of a foreign but nevertheless inner
      compulsion to move; 2. lack of control over motor behaviour; 3. feeling of
      inhibition of purposeful actions and 4. subjectively close or inseparable
      relationship between inner restlessness and restless movements. These features
      are strongly interrelated and correlate with severity of akathisia. They could be
      useful in differentiating akathisia from other states of restlessness. The
      results of this study are discussed in context of the literature on clinical
      phenomenology of akathisia. We propose a symptom-severity model of akathisia
      emphasizing psychodynamic aspects with considerable consequences for diagnosis
      and quantification of the disorder. The model points to the relevance of patient
      exploration for optimizing diagnostic reliability and should be taken into
      account when developing new and valid akathisia rating instruments.

PMID- 9922926
TI  - [Polyneuropathies from solvents].
AB  - Polyneuropathy is a clinically diagnosed disorder. The diagnostic features
      consist mainly of subjective complaints about distally marked paresthesia or
      dysaesthesia, pain and motor disturbances like cramps. Neurological examination
      typically shows weak or absent tendon reflexes (early signs: weak or absent
      Achilles tendon reflexes), distally marked disturbances of sensitivity (early
      sign: reduced sense of vibration), atrophic paresis, cranial nerve impairment and
      disturbances of the autonomic nervous system. Results of additionally performed
      electrophysiological examinations (nerve conduction studies, vibratometry and
      thermotesting) contribute to the diagnosis. Polyneuropathy is undoubtedly induced
      by carbon disulfite, ethylene glycol, n-hexane and methyl-n-butylketone,
      triorthocresyl phosphate and solvent mixtures. Induction of polyneuropathy is
      doubtful with the following substances: tetrachloride, trichlorethylene, styrene,
      toluene. Additional impairment of the central nervous system is often indicated
      by clinical findings of brisk patellar tendon reflexes or the occurrence of
      Babinski's sign.

PMID- 9922927
TI  - [The treatment history of patients with borderline personality disorder in the
      Republic of Germany].
AB  - The present study was undertaken to explore the treatment history of women with
      borderline personality disorder and to provide an estimation of the treatment
      costs. Using a semi-structured interview, forty-five carefully diagnosed patients
      were interrogated about their lifetime treatment history with respect to every
      inpatient and outpatient treatment received for any psychical symptoms, including
      physical treatment after self-injurious behaviour. Results demonstrate an
      extensive and protracted use of psychiatric, psychotherapeutic and physical help,
      and a chaotic course of treatment with discontinuance of treatments as a
      characteristic feature. Treatment costs were estimated at a minimum of 24,000 DM
      per year and patient; 22,000 DM due to hospitalisations. The unsatisfactory
      treatment situation for these patients in the public health system and the
      socioeconomic advantages of a specified treatment programme are discussed.

PMID- 9922928
TI  - [Diagnosis and differential diagnosis of sleep disorders in children].
AB  - Sleep disorders in children are very common and their impact on emotional and
      cognitive functions is considerable. Clinical work necessitates an
      interdisciplinary access to the subject because the scope of sleep medicine is
      related to various medical disciplines (e.g. paediatric neurology, pulmology and
      child psychiatry). Although many sleep problems are seen in both children and
      adults diagnoses, symptoms and pathogenetic factors are quite different in the
      two groups. In childhood especially parent-child interactional factors and
      developmental aspects of the sleep architecture and the sleep-wake cycle have to
      be taken into account leading to different diagnostic and therapeutic approaches.
      In this article we focus on important developmental aspects of childrens' sleep
      problems. Their relationship to neurologic, paediatric and psychiatric diseases
      is demonstrated and finally clear indications to diagnostic procedures,
      especially polysomnography, are given.

PMID- 9922929
TI  - [Calcium antagonistic actions of drugs used in treatment of affective disorders].
AB  - Disturbances of intra- and extracellular calcium levels are often reported during
      the course of affective disorders. In this review calcium antagonistic properties
      of drugs used in the treatment of affective disorders are discussed. The effects
      of calcium channel blockers in animal models of depression and in clinical trials
      are compared to established treatment strategies. Knowledge on changes in calcium
      homoeostasis during the treatment of affective disorders may increase the scope
      of therapeutic options.

PMID- 9922930
TI  - Laboratory evaluation of hypercoagulable states.
AB  - The number of well-characterized hereditary and acquired hypercoagulable
      conditions is increasing, such that in many thrombophilic patients, the
      laboratory can now identify a hypercoagulable condition. This review describes
      the currently known hypercoagulable states that predispose patients to venous,
      and in some instances, arterial thrombosis. For each condition, the discussion
      includes the incidence, magnitude of the thrombotic risk in the general
      population in comparison with symptomatic families, synergistic interactions
      among the various hypercoagulable conditions, molecular pathogenesis, and
      interpretation of laboratory test results. In addition, recommendations for
      laboratory testing are summarized.

PMID- 9922931
TI  - Lupus anticoagulants and antiphospholipid antibodies.
AB  - In recent years, clinical syndromes involving lupus anticoagulants and
      antiphospholipid antibodies have come into increasing clinical prominence. Since
      the discovery that most antiphospholipid antibodies require the presence of
      anionic phospholipid-binding proteins such as B2-glycoprotein I and prothrombin,
      a large number of studies have attempted to delineate the specificity of these
      antibodies. Several mechanisms have been proposed to explain the hypercoagulable
      state associated with these antibodies. This review attempts to summarize these
      data and the challenges that confront efforts to delineate the pathogenesis of
      the prothrombotic state associated with the presence of these antibodies.

PMID- 9922932
TI  - Update on genetic risk factors for thrombosis and atherosclerotic vascular
      disease.
AB  - The strong familial occurrence of venous and arterial thromboembolic disease has
      prompted ongoing research to identify novel risk factors. Polymorphisms in the
      factor VII and prothrombin genes are related to increased thrombosis, but the
      mechanism of increased risk remains to be elucidated. Elevated levels of plasma
      homocysteine and of the variant lipoprotein(a) particle also contribute to
      increased thrombotic risk, due in part to polymorphisms in the apolipoprotein(a)
      gene and the gene for methylene tetrahydrofolate reductase.

PMID- 9922933
TI  - Therapeutic inhibition of thrombin activities, receptors, and production.
AB  - Thrombin mediates acute vascular thrombosis following mechanical denuding injury
      or spontaneous rupture of atherosclerotic plaques. In the process of generating
      thrombin, factor VII/VIIa binds avidly with tissue factor exposed on cellular
      membranes, leading to sequential activation of coagulation serine proteases via
      macromolecular catalytic complexes on phospholipid surfaces. At sites of
      disrupted arteries thrombin activates platelets, blood leukocytes, endothelium,
      and vascular SMCs by cleaving G protein-coupled TRs, mediating SMC intimal
      proliferation in the formation of neointimal vascular lesions. Therapeutic
      strategies targeting thrombin include inactivation of bound thrombin, inhibition
      of TR activation by thrombin, and interruption of thrombin production. In
      patients having orthopedic surgery, inactivating bound thrombin with direct
      antithrombins markedly reduces venous thromboembolism as compared with heparin or
      its derivatives, without significant impairment of hemostasis. Antithrombotic
      effects in arterial thromboembolism, such as acute coronary syndrome, are not
      conclusively benefitted by systemic direct antithrombins when administered at
      safe levels, because interrupting TR-dependent platelet thrombosis demands
      systemic levels of direct antithrombins that compromise hemostatic function.
      Alternative safer strategies evolving from preclinical studies include (1)
      inhibiting thrombin activation of TRs, thereby abolishing platelet recruitment in
      arterial thrombogenesis, while sparing fibrin formation in hemostatic plugs; (2)
      enhancing the formation of endogenous activated protein C by protein C-selective
      thrombin mutants; and (3) preventing thrombin production by inhibiting precursor
      serine protease function and interrupting the formation of both acute thrombosis
      and vascular lesion formation. Tissue factor pathway antagonists are particularly
      promising because they exhibit both efficacy and safety in the prevention of
      thrombosis and vascular lesions.

PMID- 9922934
TI  - Antiplatelet therapy. Aspirin, ticlopidine/clopidogrel, and anti-integrin agents.
AB  - Aspirin is the most widely employed antithrombotic agent in use today and has a
      proven role in the prevention and acute management of atherosclerosis-associated
      arterial thrombotic events. More recently developed antiplatelet agents have been
      found to have specific prophylactic roles associated with percutaneous coronary
      intervention and other clinical settings. This article outlines pharmacologic
      considerations and current clinical knowledge relevant to the use of aspirin,
      ticlopidine, clopidogrel, and the GPIIbIIIa antagonists in the management of
      thrombotic disorders.

PMID- 9922935
TI  - Low-molecular-weight heparins.
AB  - Low-molecular-weight heparins (LMWH) are a new group of parenteral
      anticoagulants. They represent a major clinical advance in anticoagulation since
      the identification of unfractionated heparin (UFH) in 1922 and the introduction
      of the synthetic coumarin derivative, warfarin, in 1948. Their predictable
      pharmacokinetics, increased bioavailability, and longer plasma half-life allow
      for once- or twice-daily dosing and eliminate the need for routine laboratory
      monitoring. This simplified administration stands to alter the clinical practice
      of anticoagulation. This review high-lights recent clinical trials and focuses on
      studies comparing LMWH with the other two major anticoagulants: UFH and coumadin.

PMID- 9922936
TI  - Venous thromboembolic events in pediatric patients. Diagnosis and management.
AB  - Venous thromboembolism is a rapidly increasing secondary complication in children
      being treated for serious, life-threatening, primary diseases. Most current
      management guidelines and recommendations for imaging techniques have been
      extrapolated from the results of trials in adults. This may be less than optimal
      for children as there are important differences. The purpose of this article is
      to summarize the information on venous thromboembolism in children, and offer
      some guidelines for diagnosis, prophylaxis, and therapeutic intervention based on
      the best available evidence.

PMID- 9922937
TI  - Hemophilia. A new approach to an old disease.
AB  - The history of hemophilia diagnosis and therapy has been a turbulent one. We are
      coming full circle, back to the use of genetics as the main diagnostic tool for
      this disease. Therapeutically, the retroviruses that ravaged one generation of
      hemophiliac patients now may participate in the cure for the next generation. The
      hemophilia community hopes that the future of hemophilia care will follow a
      course guided by this modified quote from James Russell Lowell: "New times demand
      new measures, and men [and women]. As the world advances and in time outgrows the
      laws that in our fathers' [and mothers'] days were the best, doubtless after us
      some purer scheme will be shaped out by wiser man [and women] than we, made wiser
      by the steady growth of truth."

PMID- 9922938
TI  - Influences of alkaline ionized water on milk yield, body weight of offspring and
      perinatal dam in rats.
AB  - The authors previously reported that male offspring of mothers rats given
      alkaline ionized water (AKW) showed a significantly higher body weight by day 14
      after birth than did offspring of mother rats given tap water (TPW); furthermore,
      marked myocardial necrosis and fibrosis were observed particularly in the former
      male offspring at the age of 15 weeks. In the present experiment we looked for
      differences in bioparameters, namely the milk yield of mothers and suckled milk
      volume of the offspring, between the AKW- and the TPW-treated groups in order to
      reveal the factors which cause the unusual body weight gain in the offspring.
      Even though we were able to repeat our previous observation (the body weight of
      the male offspring of the AKW group increased significantly more by day 14 and 20
      after birth and of the female by day 20 after birth than did that of the TPW
      group (p < 0.05), no significant difference was noted in any of the
      bioparameters, including those related to milk production and consumption. It is
      thus suspected that the water-hydrated cation, which was transferred either to
      the fetus through the placenta or to the offspring through the milk, might be the
      cause of the unusual body weight increase. Since calcium plays an important role
      in skeletal formation, it is tentatively concluded that the higher calcium
      concentration of AKW enriched the mother, serum calcium which was transferred to
      the fetus through the placenta and to the offspring through the milk.

PMID- 9922939
TI  - Evaluation of rat sperm by flow cytometry: simultaneous analysis of sperm count
      and sperm viability.
AB  - In this study, we conducted a simultaneous analysis of sperm count and viability
      in rats by flow cytometry (FCM). Epididymal fluids were taken from the caudal
      epididymis of 12 to 13 week-old Sprague-Dawley rats. The fluids were weighed and
      mixed with Dulbecco's phosphate buffered saline (D-PBS). Propidium iodide, which
      can stain only dead sperm, was used to distinguish viable and dead sperm. The
      sperm count and viability analyzed by FCM were 1.28 x 10(6)/mg and 78.0%,
      respectively. These values were consistent with the corresponding values (1.39 x
      10(6)/mg and 81.0%) that were directly determined microscopically in the fluids
      of the same sample. In addition, when the original mixture containing sperm was
      diluted two times and four times with D-PBS, or was diluted two times with D-PBS
      containing only killed sperm, the sperm count and viability determined by FCM
      also correlated well with the sperm count (r = 0.96, P < 0.01) and sperm motility
      (r = 0.99, P < 0.01) by direct microscopic observation, respectively. In
      conclusion, the present flow cytometric analysis would be practical for the
      simultaneous determination of sperm count and viability in rat epididymal fluids.

PMID- 9922940
TI  - Methylmercury-induced microtubule depolymerization leads to inhibition of tubulin
      synthesis.
AB  - Methylmercury (MeHg) specifically depolymerizes microtubules and inhibits cell
      proliferation in mouse glioma cells. The effect of microtubule depolymerization
      by MeHg on tubulin synthesis was studied. Tubulin synthesis analyzed by two
      dimensional electrophoresis using [35S]methionine as a tracer was markedly
      inhibited in mouse glioma cells exposed to 5 x 10(-6)M MeHg for 3 hr, which
      completely depolymerized microtubules. Under this condition, density of the
      protein bands other than tubulin in autoradiogram remained unchanged on gradient
      urea-polyacrylamide gels. Furthermore, the decrease in tubulin mRNA level was
      relevant to that in tubulin synthesis, although actin mRNA levels remained
      unchanged. In addition, specific transcription rates of beta-tubulin genes
      appeared to be unaffected under the same experimental condition as above. Thus,
      it is concluded that the disruption of microtubules by MeHg resulted in the
      inhibition of the synthesis of tubulin itself through autoregulatory repression
      in post-transcriptional processes as in the case of colchicine treatment.

PMID- 9922941
TI  - NO depletes cellular ATP contents via inactivation of glyceraldehyde-3-phosphate
      dehydrogenase in PC12 cells.
AB  - Recently, we demonstrated that nitric oxide (NO) reduces ATP generation via
      oxidative phosphorylation coupled with the mitochondrial respiratory chain in
      PC12 cells resulting in induction of apoptotic cell death. To further study the
      correlation between NO-induced ATP depletion and neuronal death, we examined the
      effect of NO on glycolytic ATP generation in PC12 cells, a neuronal model. When
      the oxidative phosphorylation was maximally suppressed by DNP and oligomycin,
      which are inhibitors of the mitochondrial respiratory chain, the cellular ATP
      contents were reduced by sodium nitroprusside (SNP). In addition, the cellular
      ATP contents were further decreased along with a decrease in the activity of
      glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a key enzyme in the glycolytic
      pathway. Benzamide, an inhibitor of poly (ADP-ribose) synthetase, could protect
      the depletion of NAD but had no effect on the depletion of ATP in PC12 cells
      induced by NO. These results suggest that the depletion of ATP in PC12 cells
      caused via the inhibition of G3PDH by NO is one of the mechanisms responsible for
      NO neurotoxicity.

PMID- 9922942
TI  - Induction of rat hepatic cytochromes P450 by toxic ingredients in plants: lack of
      correlation between toxicity and inductive activity.
AB  - "Animal-Plant Warfare" is one of the hypotheses for the evolution of drug
      metabolizing P450s. To address the validity of this hypothesis, we examined the
      induction of xenobiotic-metabolizing P450s by 12 plant toxins in rats, using
      hepatic activity for testosterone metabolism as the index. The compounds tested
      were aconitine, morphine, tubocurarine, physostigmine, pilocarpine, muscarine,
      cocaine, atropine, amygdalin, digitonin, nicotine and solanine. Drinking water
      containing a test compound was given to rats for 4 days, and the hepatic activity
      of testosterone metabolism was determined together with monitoring body weight
      gain and liver weight as the indices of toxicity. The results showed that while
      cocaine and nicotine have a minor ability to increase testosterone 16 beta
      hydroxylase activity, a marker activity for the CYP2B1 and 2, all other compounds
      did not have any such effect. No correlation was observed between a change in 16
      beta-hydroxylase and toxicity caused by toxins. Therefore, these results did not
      support the idea that the inducibility of the CYP2B subfamily in animals is
      acquired through "Animal-Plant Warfare". Several compounds examined here
      increased or decreased hepatic activities of testosterone 2 alpha-, 6 beta-, 7
      alpha- and 16 alpha-hydroxylation and 17-oxidation, indicating a possible effect
      on the CYP2A, 2C and 3A subfamily. Of these effects, a moderate correlation (r <
      0.49) was observed in the changes in the activities of 2 alpha-/16 alpha
      hydroxylation and 17-oxidation vs. that in toxicity. It is therefore suggested
      that inhibition or suppression of the expression of CYP2C11 is one of the
      mechanisms in the toxicity of plant toxins for rats, although it comes from an
      examination using limited numbers of compounds.

PMID- 9922943
TI  - Studies of repeated administration of FK-506 on myocardial metabolism in rats.
AB  - The effect of a 14-day administration of FK-506 at 1 or 3 mg/kg on plasma lipids
      and myocardial energy and glucose metabolism in rats was investigated. FK-506
      increased the level of blood glucose in rats when given daily at an oral dosage
      of 3 mg/kg for 14 days. The plasma level of total cholesterol was significantly
      increased by FK-506 at either 1 or 3 mg/kg, whereas that of triglyceride was not
      changed. There was no significant difference in energy charge potential and the
      lactate/pyruvate ratio of the myocardial tissue between FK-506- and solvent
      treated groups. Because FK-506 administration for 14 consecutive days did not
      disturb myocardial energy and glucose metabolism, its cardiotoxic side effects
      were not recognized in the present experimental toxicological evaluation of rats.

PMID- 9922944
TI  - Histopathological influence of alkaline ionized water on myocardial muscle of
      mother rats.
AB  - We have reported that a marked necrosis and subsequent fibrosis of myocardium
      occurred among male rats 15 weeks old given alkaline ionized water (AKW) during
      gestation and suckling periods, and after weaning. In this study, it was examined
      whether similar lesions would occur in mother rats which were given AKW from day
      zero of gestation to day 20 of lactation. The myocardial lesion in the mother
      rats given AKW showed cell infiltration, vacuolation and fibrosis in the
      papillary muscle of the left ventricle, as were observed in male rats of 15 weeks
      old. Myocardial degeneration may cause a leakage of potassium into the blood that
      results in a higher concentration of potassium in the blood in the test group
      than in that of the control group given tap water.

PMID- 9922946
TI  - Evaluation of allergenic potential of low-molecular compounds by mouse popliteal
      lymph node assay.
AB  - In the present study, the correlation between mouse PLNA results and those
      obtained from GP-PCA and from GP-ASA reactions for sodium 2,4,6
      trinitrobenzenesulfonate dihydrate (TNBS), penicillin G and cephalothin was
      investigated. Next, various drugs were tested using the mouse PLNA to study
      whether PLN reactivity could be related to the potential of the compounds to
      induce allergic and autoimmune disorders in humans. The parameter of the PLNA was
      determined by the PLN cellularity index in BALB/c and A/J mice treated with a
      single subcutaneous injection of compounds. Hartley guinea pigs were immunized
      subcutaneously with the compounds without adjuvant, and then the GP-PCA and GP
      ASA reactions were assessed. The examinations using mice and guinea pigs showed
      that mouse PLN responses to TNBS, penicillin G and cephalothin correlated with
      the allergenicity responses obtained in the GP-PCA reaction to three compounds.
      In the mouse PLNA, ten drugs considered to be well-known inducers of allergic
      side-effects in humans (i.e., penicillin G, cephalothin, ampicillin,
      carbenicillin, cefazolin, cefotaxime, streptomycin, 4-aminoantipyrine,
      chlorhexidine and sulfamethoxazole) caused increases in PLN cellularity indices
      as well. These results indicate that the PLNA may be useful as a short-term and
      simple test system for detecting low-molecular drugs exhibiting allergenicity
      potential.

PMID- 9922945
TI  - Effect of the spine venom from the crown-of-thorns starfish, Acanthaster planci,
      on drug-metabolizing enzyme in rat liver.
AB  - The effect of spine venom from the crown-of-thorns starfish (Acanthaster planci)
      on drug-metabolizing enzymes in rat liver was studied. The spine venom was
      prepared by saturation of spine homogenate with ammonium sulfate and the protein
      fraction precipitating 50% saturation was used as venom B. Venom A was the
      protein precipitated between 50 and 100% saturation. When venom B (100-200 mg/kg)
      was given to rats, liver microsomal GSH S-transferase and cytochrome P450
      activities decreased while cytosolic GSH S-transferase activity was not changed.
      The decrease in these microsomal enzyme activities was seen from 12 hr to 24 hr
      after giving 100 mg/kg of venom B. Rats given venom A died, suggesting an
      involvement of the lethal factor in venom A. The data showed that the spine venom
      B from A. planci depressed microsomal GSH S-transferase and cytochrome P450
      activities in rat liver and that this venom was distinct from the lethal factor
      of the spine venom.

PMID- 9922947
TI  - Sequential alterations in clinical biochemical indicators of renal function in
      5/6 nephrectomized rats--basic study for renal toxicity using 5/6 nephrectomized
      rats.
AB  - It has been established that progression of renal lesions in 5/6 nephrectomized
      rats, in which the total right kidney was removed and two poles of the left
      kidney were excised surgically, and are used as an animal model of renal failure
      in man, can be morphologically divided into three stages. In the present study,
      for establishing a renal toxicity study using this animal model on the
      physiological side, changes of biochemical parameters were sequentially
      investigated in 20 male 5/6 nephrectomized Wistar rats until 26 weeks after
      nephrectomy. Creatinine clearance (CLcre) and water as well as electrolyte
      reabsorption (FRwater and FR Na, K, Cl) were reduced at weeks 2-4, then increased
      slightly from weeks 6 to 10, and reduced again thereafter. On the contrary,
      urinary protein was elevated throughout the experimental period, while albumin
      fraction was increased after week 2 and low-molecular tubular protein increased
      after week 6 by electrophoresis. Urinary LDH also demonstrated high levels
      throughout the observation period, but ALP only increased after week 18. The
      present study thus confirmed that renal function after 5/6 nephrectomy is indeed
      changed in three stages with clinical biochemical parameters, especially CLcre
      and FR Na, K, Cl being good indicators to distinguish the three stages of
      glomerular and tubular dysfunction, respectively. In addition, urinary protein
      fractions by electrophoresis in this animal model were examined for the first
      time, proving useful approach to glomerular and tubular dysfunction.

PMID- 9922948
TI  - Hippocrates: an integrated platform for telemedicine applications.
AB  - This paper describes 'Hippocrates', an integrated platform for telemedicine
      applications. Hippocrates allows computer supported co-operative work based on
      patient data folders consisting of selected diagnostic images, annotation text,
      patient history and other information. All data transferred is encrypted to
      ensure confidentiality and integrity. It operates on a local level over TCP/IP
      LAN environment and on a remote level over public ISDN lines.

PMID- 9922949
TI  - A network-based training environment: a medical image processing paradigm.
AB  - The capability of interactive multimedia and Internet technologies is
      investigated with respect to the implementation of a distance learning
      environment. The system is built according to a client-server architecture, based
      on the Internet infrastructure, composed of server nodes conceptually modelled as
      WWW sites. Sites are implemented by customization of available components. The
      environment integrates network-delivered interactive multimedia courses, network
      based tutoring, SIG support, information databases of professional interest, as
      well as course and tutoring management. This capability has been demonstrated by
      means of an implemented system, validated with digital image processing content,
      specifically image enhancement. Image enhancement methods are theoretically
      described and applied to mammograms. Emphasis is given to the interactive
      presentation of the effects of algorithm parameters on images. The system end
      user access depends on available bandwidth, so high-speed access can be achieved
      via LAN or local ISDN connections. Network based training offers new means of
      improved access and sharing of learning resources and expertise, as promising
      supplements in training.

PMID- 9922950
TI  - A multi-agent architecture for teaching dermatology.
AB  - This work proposes the integration of computer-aided instruction systems in the
      curricula of medical education, and describes an intelligent tutoring system used
      for teaching Dermatology. The Dermatology Tutor uses a self-organized society of
      autonomous software agents which have different capabilities or roles. The
      society contains tutor, medical and information agents which participate in the
      tutoring process and collaborate through deliberation in order to achieve a
      tutoring task. The agents are built according to a BDI architecture, which
      implements the mental attitudes of beliefs (B), desires (D) and intentions (I).
      Each medical agent is a specialist in a medical field, while a tutoring agent,
      which implements a widely accepted dermatology teaching process, coordinates the
      overall operation of the system. Depending on the subject that is to be taught
      during any session, the tutoring agent forms teams of medical agents, which in
      turn use search agents to retrieve information. Although the presented multi
      agent architecture is dedicated to teaching dermatology (since the tutor agent is
      specialized in Dermatology), it can be extended to other domains also with the
      incorporation of other tutor agents.

PMID- 9922951
TI  - Enhancing security and improving interoperability in healthcare information
      systems.
AB  - Security is a key issue in healthcare information systems, since most aspects of
      security become of considerable or even critical importance when handling
      healthcare information. In addition, the intense need for information exchange
      has revealed interoperability of systems and applications as another key issue.
      Standardization can play an important role towards both these issues. In this
      paper, relevant standardization activities are briefly presented, and existing
      and emerging healthcare information security standards are identified and
      critically analysed. The analysis is based on a framework which has been
      developed for this reason. Therefore, the identification of gaps and
      inconsistencies in current standardization, the description of the conflicts of
      standards with legislation, and the analysis of implications of these standards
      to user organizations, are the main results of this paper.

PMID- 9922952
TI  - Backpropagation and adaptive resonance theory in predicting suicidal risk.
AB  - The ability of backpropagation and adaptive resonance theory (ART) neural
      networks to predict the probability of complete suicide, within a two year span,
      in major psychiatric patients was investigated. Variables associated with suicide
      risk were collected from the files of 161 hospitalized psychiatric patients with
      a 10 year or greater history of illness. 84 patients were hospitalized due to
      suicide attempts and 77 had no previous suicide attempts or ideations. Suicide
      attempts were rated as medically serious suicide attempts (MSSA) or non-MSSA and
      used for training the systems. The ability of the neural networks was evaluated
      by screening the extremes of the suicidal spectrum (1) 54 records of patients who
      committed suicide and (2) 150 records of patients who never had suicidal
      thoughts. The records were taken from 3 hospitals, in various geographic regions
      in Israel. Neither neural network system is reliable in predicting suicide,
      however, records from one hospital, Gehah Hospital, were better identified than
      those from the two other hospitals (p < 0.05 for PPV; p < 0.01 for specificity).
      At present, neural networks are not reliable instruments for evaluating suicidal
      risk due to the significant number of false positive results. When low risk was
      indicated reliability was greater (NPV = 75.28%, specificity = 97.10% with ART;
      NPV = 91.76%, specificity = 95.12% with backpropagation). However, PPV, NPV and
      specificity rates of both systems achieved with Gehah Hospital records suggest
      that using a direct-subjective questionnaire may produce better results in the
      future. ART and backpropagation performed similarly in all measurements.

PMID- 9922953
TI  - [Tuberculosis in AIDS patients: the contribution of an analysis of the
      restriction fragment length polymorphism of Mycobacterium tuberculosis isolates].
AB  - BACKGROUND: In this report we study tuberculosis transmission in HIV infected
      patients using molecular epidemiological methods. PATIENTS AND METHODS: We have
      studied 60 M. tuberculosis isolates from 30 HIV infected cases, and their
      clinical-epidemiological data. Susceptibility to tuberculostatic agents and
      electrophoretic patterns using RFLPs (restriction fragment length polymorphisms)
      method were evaluated. Dice's coefficient was used for the similarity analysis.
      RESULTS: Over 73% studied patients were included in clusters using RFLPs
      analysis. This data show that nearly 60% of the tuberculosis cases in our area
      have a recent transmission. Forty per cent of these cases were included in the
      main cluster. The frequency of tuberculostatic-resistant strains in HIV infected
      patients was similar to the that of observed in other patients. We did not find
      correlation between RFLPs clusters and clinical-epidemiological data.
      CONCLUSIONS: Tuberculosis transmission in HIV-positive patients using RFLPs as
      molecular marker shows that 60% of the cases are caused by recently acquired
      strains. We did not find multi-drug resistant strains in our isolates. However
      due to the high transmissibility of these circulating clones, control disease
      measures in this group of risk population are required.

PMID- 9922954
TI  - [Pulmonary cavitation lesions in patients infected with the human
      immunodeficiency virus: an analysis of a series of 78 cases].
AB  - BACKGROUND: To assess the clinical, radiologic and microbiological features of
      lung cavitation and HIV infection. Evaluation of the differences related to this
      disease in the last years. PATIENTS AND METHODS: Retrospective review of all
      patients with lung cavitation and HIV infection admitted at our hospital from
      January 1989 until December 1994 and prospective study of all patients with the
      same characteristics during 1995 and 1996. Lung cavitation was defined as any
      parenchymal lesion, with air content, visible in a simple X-ray and greater than
      1 cm of diameter. Criteria for confirmed, probable or possible diagnosis were
      defined. RESULTS: 78 cases of lung cavitation have been identified in 73
      patients. The radiologic patterns included unilobar and multilobular involvement
      in 31 and 47 cases, respectively. Cavities were multiple and single in 40 and 38
      cases respectively. Findings with fine needle aspiration biopsy (FNAB) were
      diagnostic in 11 out of 14 cases. A clinical diagnosis was performed in all 78
      cases, with microbiological results in 69 cases (88.5%): Mycobacterium
      tuberculosis in 20, Pneumocystis carinii in nine, Pseudomonas aeruginosa in nine,
      Staphylococcus aureus in eight (5 endocarditis with cavitary septic emboli),
      Rhodococcus equi in six, P. aeruginosa and S. aureus in three, Salmonella
      enteritidis in three, Cryptococcus neoformans in two, Aspergillus fumigatus in
      two and others in 7 cases. Confirmed, probable and possible diagnosis was
      considered in 54, 15 and 9 cases, respectively. Thirteen episodes of spontaneous
      pneumothorax were found. CONCLUSIONS: The lung cavitation rate is low, compared
      with the number of admissions related to HIV infection; nevertheless, many of
      them are in close relationship with HIV infection, and most of them are caused by
      treatable infections. It is important to know the clinical and radiological
      characteristics, in order to establish an early diagnosis and an appropriate
      therapy. Pseudomonas aeruginosa is becoming an important cause of lung
      cavitation. In our series, spontaneous pneumo-thorax was not related to
      Pneumocystis carinii pneumonia in 61.5% of cases.

PMID- 9922955
TI  - [The epidemiological surveillance of human immunodeficiency virus (HIV) infection
      in a hospital population of Catalonia. Collaborators in the VIHHOSP project].
AB  - BACKGROUND: AIDS is one of the most important problems of public health in our
      setting. The surveillance of HIV infection in sentinel population is an important
      alternative to the use of the AIDS cases registries, to obtain a dynamic and
      updated information about HIV/AIDS epidemic. The objective of this study was to
      determine the prevalence of HIV infection among the patients from 5 sentinel
      hospitals in Catalonia, Spain. PATIENTS AND METHODS: Unlinked anonymous screening
      of serum from patients aged 15-49 from 5 sentinel hospitals in Catalonia, Spain.
      Samples were broken by age, sex, in-patients or out-patients and clinical
      specialities related to HIV/AIDS or not related. Samples were analyzed in pools
      of five and were tested by the OMS strategy II, for the epidemiological
      surveillance purposes. RESULTS: HIV testing was developed in 9,524 patients, with
      a prevalence of 1.6% (153 samples). The overall prevalence in men was twice that
      of women (2.3% vs. 1.1%). Ages between 25 to 34 had the higher prevalence (3.1%).
      Clinical specialities related with HIV/AIDS had a prevalence twice that of non
      related (2.3% vs. 1.2%). CONCLUSIONS: The HIV prevalence found in this population
      is the highest compared to similar studies performed in other western european
      countries. Our data confirm the pattern of HIV infection for age and sex observed
      in other studies in Catalonia, Spain. This is the first study of sentinel
      surveillance in sentinel hospitals in Spain and give us the base line which will
      serve as a reference to assess the evolution of HIV infection in further studies
      in sentinel hospital populations in Catalonia.

PMID- 9922956
TI  - [The antithrombotic treatment of acute ischemic stroke: a problem solved?].

PMID- 9922957
TI  - [50 years of LE cells: is it time for their retirement?].

PMID- 9922958
TI  - [Training in communication and informed consent in our residency system: what
      information can and should the resident give?].

PMID- 9922959
TI  - [Hypothyroidism in the elderly patient: its clinical significance and
      difficulties in diagnosis and treatment].

PMID- 9922960
TI  - [The nephrotic syndrome, AA amyloidosis and a retroperitoneal tumor mass in a 20
      year-old female patient].

PMID- 9922961
TI  - [Intensive insulin treatment improves metabolic control and preserves residual
      insulin secretion at 5 years from the diagnosis of type-1 diabetes mellitus].

PMID- 9922962
TI  - [The lipid-lowering treatment of ischemic cardiopathy and primary care].

PMID- 9922963
TI  - [Triple treatment for the eradication of Helicobacter pylori infection].

PMID- 9922964
TI  - [Bacteremia due to vancomycin-resistant enterococci in neutropenic cancer
      patients].
AB  - BACKGROUND: The aim of this study was to determine the incidence, clinical
      characteristics and outcome of vancomycin-resistant enterococcal bacteremia.
      PATIENTS AND METHODS: We included all cases of enterococcal bacteremia in
      neutropenic cancer patients documented between January 1986 and December 1995 in
      a 1,000-bed university hospital, where a prospective surveillance of all cases of
      bacteremia is regularly done. Molecular typing was performed on all vancomycin
      resistant strains with the analysis of chromosomic DNA by macrorestriction.
      RESULTS: Seventeen cases of enterococcal bacteremia were documented. Seven (41%)
      were caused by vancomycin-resistant strains (E. faecium 3 and E. gallinarum 4),
      six of which occurred in the last 5 years of the study period. The average age of
      patients was 43 years (18-69) and most of them had acute leukemia. Eighty percent
      of these patients had received vancomycin and/or cephalosporins within 2 weeks
      prior to bacteremia. Previous administration of antibiotics was more frequent in
      patients with bacteremia caused by vancomycin-resistant enterococci than in those
      with bacteremia caused by susceptible strains (86% vs 30%; p < 0.05). The mean
      number of previous antibiotics (2.4 vs 0.8; p < 0.05) as well as days of
      treatment (13.6 vs 4.3; p = 0.05) were also higher among patients with resistant
      enterococcal bacteremia. The overall mortality was 57%. CONCLUSIONS: This study
      shows the emergence of sporadic cases of bacteremia caused by vancomycin
      resistant enterococci in neutropenic cancer patients in our area. This fact seems
      to be related with the previous administration of antibiotics and advice that a
      rational use of these agents is needed.

PMID- 9922965
TI  - [Primary septicemias in pediatric patients. Hospital Infantil de la Paz (1990
      1993)].
AB  - BACKGROUND: Septicemias comprise more than one third of nosocomial infections in
      children. Their risk factors are related with the exposition time, therefore they
      are evaluated in relationship to it. PATIENTS AND METHODS: Prospective
      observational study along 4 years in surgical children and in those entered in
      the Internal Medicine Unit patients of a children Hospital, with stays higher
      than two days. Data were collected from admission to discharge. Bivariant
      analysis of stay time until infection with Wilcoxon-Gehan test, followed by Cox
      regression with time interaction terms for the risk factors that did not fulfill
      the requisite of proportional risks. RESULTS: 4,098 children were studied. 3.8%
      suffered primary septicemia and more than one half had coagulase-negative
      staphylococci. Cox regression showed the following risk factors: type of surgery,
      peripheral and central venous catheter, urinary catheterization, stay previous to
      surgery and duration of intervention. The protection factors were more than 3
      days of antibiotherapy, age higher than 1 year and male sex. The factors with
      interaction with time were: stay previous to surgery, sex and duration of
      intervention. CONCLUSIONS: The stay previous to surgery, antibiotherapy reduction
      and duration of instrumentations are risk factors susceptible to be modified in
      order to reduce the incidence of infection in children. Protection by means of
      antibiotics requires to be evaluated through an ad hoc designed study.

PMID- 9922966
TI  - [The effect of a race 4 hours in duration on the production of beta-endorphin and
      adrenocorticotropic hormone].
AB  - BACKGROUND: Physiological hormone adaptation to a prolonged and submaximum
      exercise is not well known. The present study was designed to evaluate changes in
      plasma levels of beta-endorphin and ACTH before and after a 4 hour pedestrian
      race. SUBJECTS AND METHOD: Fourteen amateur athletes enrolled in a 4-hour race
      were studied. Beta-endorphin and ACTH determinations were performed (double
      antibody IRMA) 10 minutes before and after the race. Simultaneously, heart rate
      and blood pressure were registered. RESULTS: After the race beta-endorphin level
      increased 2.8 times with respect to basal values (X [DE]) (42.2 [20,5] VS 14.9
      [5.1] pM/I; p < 0.0001), and ACTH level increased 3.5 times (110.8 [72.9] vs 31.4
      [14.2] pg/ml; p < 0.0001). There was a positive correlation between the increase
      of beta-endorphin and ACTH and the distance covered by each athlete (r = 0.617, p
      < 0.001 and r = 0.533, p < 0.05, respectively), and between the increase of basal
      and post-race values of both hormones (r = 0.935; p < 0.001). CONCLUSION:
      Prolonged and submaximum exercise provokes beta-endorphin and ACTH increase, and
      is related to the amount of performed exercise. There is a positive correlation
      between the increase of plasma levels of both hormones. Therefore, exercise
      amount could be one of the main modulator mechanism of beta-endorphin and ACTH
      release.

PMID- 9922968
TI  - [Thrombocytopenia in the antiphospholipid syndrome].

PMID- 9922967
TI  - [Acute renal failure in the allogeneic transplantation of hemopoietic
      progenitors. The clinical characteristics in a series of 92 patients].
AB  - BACKGROUND: Analysis of clinical characteristics of acute renal failure (ARF)
      after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS:
      Analysis of 92 patients who developed ARF of 260 patients following BMT. RESULTS:
      ARF incidence was 35.4%. Sixty three percent of ARF occurred before day 20 after
      BMT. Duration of ARF was less of 10 days in 72.8%. ARF was non oliguric in the
      80.4% of cases. Most common ARF etiologies were: multifactorial (37%),
      nephrotoxicity (NPH) (33.7%) and veno-occlusive disease of the liver (VOD)
      (14.1%). ARF secondary to VOD was the most severe: and the longest, where the
      secondary to NPH was less lever and shorter. Hemodialysis (HD) was necessary in
      22.8% of ARF. Mortality in ARF group was 45.6%, higher in HD group (80.9%) than
      in non-HD group (35.2%) (p < 0.0002). CONCLUSIONS: ARF is a frequent complication
      following BMT. It occurs early, has short duration, is non oliguric, mainly
      hemodynamic and carries a whose prognosis.

PMID- 9922969
TI  - [The attitude in a failure to eradicate Helicobacter pylori: surrender or
      fight?].

PMID- 9922970
TI  - [1998: the year of Dr. A. Pedro-Pons].

PMID- 9922971
TI  - [Systemic autoimmune diseases during pregnancy: a practical approach].

PMID- 9922972
TI  - [The intrathoracic hypertension syndrome in a breath-hold diver].

PMID- 9922973
TI  - [Tha markers of secondary uveitis].

PMID- 9922974
TI  - [Tuberculosis and uveitis].

PMID- 9922975
TI  - [ASCUS cytological diagnosis: its value in patients with antecedent
      intraepithelial squamous lesions. Atypical squamous cells of undetermined
      origin].

PMID- 9922976
TI  - [Tumor markers and gastric cancer. TAG-72 is the most useful].

PMID- 9922977
TI  - [Waldenstrom's macroglobulinemia and primary cerebral diffuse large-cell
      lymphoma].

PMID- 9922978
TI  - [Diabetes mellitus and protease inhibitors. A complication to take into account].

PMID- 9922979
TI  - Antimurine retroviral effect of doxycycline.
AB  - The tetracycline family is composed of several molecules whose antibacterial
      properties are due to the fixation on the bacterial ribosomes. Among those,
      doxycycline is one of the most potent antibiotics for which additional features
      have been recently discovered. Doxycycline has been found to inhibit
      metalloproteinases, to decrease gelatinolytic and metastatic activities of cancer
      cells, to have a "chondroprotective" effect in inflammatory arthritides, and to
      have strong antimalarial properties. In this study, a murine retrovirus producing
      cell line (psi CRIP-pXT1) was incubated in variable concentrations of
      doxycycline. The retroviral titer of this cell line was measured by the ability
      to transfer resistance to G418 to NIH/3T3 cells. The retroviral titer was
      significantly decreased by 70% when the packaging cells had been incubated with
      25 microM of doxycycline at 37 degrees C. The ID50 was around 8 micrograms/ml.
      Astonishingly, this effect was not observed at 32 degrees C. The mechanism of
      this effect is still to be determined. It may be useful to be aware of this
      effect for uncovering all of the possible antiviral qualities of doxycycline and
      its related molecules, such as glycylcyclines or anthracyclines.

PMID- 9922981
TI  - Sympathetic and platelet adrenergic activity and salt sensitivity: an
      experimental study.
AB  - The objective of the study was to evaluate the advanced hypothesis that
      genetically predisposed salt-sensitivity contributes to an increased adrenergic
      susceptibility and platelet activity and both these factors play a role in the
      pathogenesis of hypertension in a Dahl rat model. The results showed: i) Dahl
      salt-sensitive rats (DS) gradually develop a diastolic hypertension by the end of
      3 months of age, in spite of the diet they are fed. Low-Na diet (0.5% NaCl) does
      not prevent hypertension but delays its development. High-Na diet (8%)
      exacerbates their hypertension. ii) After 2 months of Na-loading, DS rats
      expressed significantly increased sodium and water retention and increased plasma
      volume by 15%, compared with 2.8% in Dahl salt-resistant (DR) rats on high-Na
      diet. iii) The increased activity of the sympathetic nervous system (SNS) in DS
      rats paralleled the development of hypertension and was stimulated by Na-loading.
      It was assessed by their catecholamines status and heart rate changes. iv)
      Platelet activity of DS rats was increased as reflected in collagen-induced
      nonstimulated and adrenaline-stimulated aggregation, and an increased plasma T x
      B2/6-keto PGF1 alpha ratio. Na-loading further increased platelet activity. v)
      Both DR and DS rat platelets displayed alpha 2-adrenoceptors (A2) of low binding
      capacity (Bmax 25 and 35 fmol/mg protein, respectively) and low affinity (KD 5.6
      nM for both groups), suggesting that platelet alpha 2 adrenoceptors in this
      strain of rats might not play a significant biological role in their increased
      platelet activity. The fact that platelet alpha 2-adrenoceptors do not define the
      stimulation of SNS in DS rat do not exclude their participation in development of
      salt-dependent hypertension, since a genetic defect(s) of these ubiquitous
      receptors (brain, kidney, blood vessels) could still contribute to the
      pathogenesis of the disease.

PMID- 9922980
TI  - The role of oxygen free radicals in isoniazid-induced hepatotoxicity.
AB  - Isoniazid and its metabolites acetylisoniazid, hydrazine and monoacetylhydrazine
      were investigated for generation of oxygen free radicals during incubation with
      rat liver slices. Lipid peroxidation was assessed by the thiobarbituric acid
      reactive substances test using malonaldehyde as the external standard, while
      hepatotoxicity was assessed by histopathology studies. Malonaldehyde formed in
      liver slices after 10 hours of incubation with the drugs was 1.28 +/- 0.24
      nmol/mg for isoniazid (control 1.12 +/- 0.17 nmol/mg); 0.88 +/- 0.45 nmol/mg for
      acetylisoniazid (control 0.84 +/- 0.42 nmol/mg); 1.43 +/- 0.14 nmol/mg for
      monoacetylhydrazine (control 1.10 +/- 0.12 nmol/mg) and 1.36 +/- 0.02 nmol/mg for
      hydrazine (control 1.13 +/- 0.04 nmol/mg). Histologically, all slices exhibited
      hepatic necrosis by 4 hours. However, hydrazine-induced hepatotoxicity was
      characterized by nuclear hyperchromatsia, karyolysis and karyohexis while
      monoacetylhydrazine exhibited hydropic karyomegaly only. Isoniazid and
      acetylisoniazid cytotoxicity exhibited a mixture of the above features such that
      it could be attributed to the two metabolites, hydrazine and monoacetylhydrazine.
      In conclusion, there was no evidence implicating oxygen free radicals in
      isoniazid-induced hepatotoxicity; however, the histopathology findings indicate a
      need for a review of our knowledge on pathognomonic features of isoniazid
      hepatotoxicity.

PMID- 9922982
TI  - Effect of roxatidine bismuth citrate (MX1) against acetylsalicylic acid- and
      indomethacin-induced gastric mucosal damage in rats.
AB  - We have studied the effect of the newly synthesized agent, roxatidine bismuth
      citrate (N-[3-(3-(1-piperidinyl-methyl)phenoxy)propyl]-hydroxyacetamide-2-
      hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex), code name MX1, against
      acetylsalicylic acid (ASA)- and indomethacin-induced gastric mucosal damage in
      rats. Effects of MX1 (12.5, 50, 125, 184, 250 mg/kg) were compared to the effects
      of equimolar doses of roxatidine and bismuth subcitrate. Effect of MX1 (10(-6) M)
      on mucin biosynthesis measured by [3H] glucosamine incorporation in rat gastric
      corpus has been determined. MX1-pretreatment dose-dependently decreased the mean
      ulcer number and length in all doses used in an extent similar to that of
      roxatidine and more pronounced in comparison with bismuth subcitrate. The
      morphometrical results have been confirmed histomorphologically. The biosynthesis
      of mucin was found to be significantly enhanced after MX1 addition. The results
      of the present study suggest that MX1 has a gastroprotective effect against ASA-
      and indomethacin-induced ulcers which might be due both to its H2-blocking and
      mucus-stimulating activity.

PMID- 9922983
TI  - Influence of testosterone on some behavioral reactions of male immature rats.
AB  - The complicated reflex complexes on the basis of orientation exploratory
      behavior, emotional state and pain reaction play an important role in the
      analisator activity of the brain cortex. The rate of inhibition of orientation
      exploratory reactions shows the intensity of the inner inhibition. In a complex
      with other indicators it can characterize the intensity and the mobility of the
      basic nerve processes of the cortex. The role of the neurosteroids has not been
      studied sufficiently in this direction. The results of the present study show the
      role of testosterone in the regulation of the horizontal and vertical locomotor
      activity and the latent period of the pain reaction of male immature rats. They
      are part of an investigation on the role of neurosteroids in adaptive reactions.
      The indicator entropy of the behavior as a characteristic of the organization of
      the behavior of rats in an open field study together with the probability
      structure of the behavior was also used. Testosterone was found to inhibit the
      horizontal and vertical locomotor activity of rats and prolong the latent period
      of the pain reaction in the tail flick test. The effect of the neurosteroid was
      apparent 4 hours after injection and was maintained for 24 hours. It was
      concluded that testosterone might play a role in the regulation of the locomotor
      behavioral acts and of the pain reaction. Testosterone influences all the
      organization of the behavior, it decreases the entropy of the behavior which is
      connected with a precipitation of the process of inhibition of the exploratory
      activity and the emotion reactivity, simultaneously changing the dynamic of the
      behavioral entropy.

PMID- 9922984
TI  - The role of cholecystokinin (CCK), CCK-A or CCK-B receptor antagonists in the
      spontaneous preference for drugs of abuse (alcohol or cocaine) in naive rats.
AB  - A "free choice" two-bottle drinking test paradigm was implemented in naive adult
      male Wistar rats, resulting in a clear identification of rats drinking mainly
      water (water-preferring, WP rats) and rats spontaneously drinking also a
      consistent amount of a solution of cocaine (0.5 mg/ml water, cocaine-drinking, CD
      rats) or ethanol 10% v/v (ethanol-drinking, ED rats). Low, selective doses (5
      micrograms/kg) of the specific cholecystokinin (CCK)-A receptor antagonist L
      364,718 largely reduced the intake of ethanol 10% of ED rats only. In contrast,
      low, selective doses of GV-150013 (5 micrograms/kg) reduced significantly the
      consumption of cocaine of CD rats only. These results indicate that the CCK-A or
      B receptors are selectively involved in the modulation of alcohol or cocaine
      intake, respectively, and suggest an involvement of the CCKergic system in the
      drug-seeking behavior. WP rats and CD rats were then prepared for ex vivo electro
      neurochemical analysis by means of differential pulse voltammetry (DPV) with
      micro-biosensors to monitor catechol, 5-hydroxyindole and peptidergic oxidation
      signals in the nucleus accumbens (nAcc). In this area, the peptidergic signal
      appeared to be related to the oxidation of endogenous CCK, which basal levels
      resulted higher in ED and CD rats than WP rats. Thus, the hypothesis that the
      endogenous tone of the CCK system is higher in the ED and CD rats than in the WP
      rats is proposed, and is supported by the observation that treatment with CCK-5
      (CCK receptor agonist) selectively induced the WP rats to drink alcohol or
      cocaine. The selective effect of the CCK-antagonists on reducing the drug intake
      of ED or CD rats further supports this view, as it suggests that CCK antagonists
      may modify the individual sensitivity towards drugs of abuse set by the
      stimulating effect of high endogenous CCKergic tone over CCK-B or CCK-A receptors
      in spontaneous ED or CD rats, respectively. Therefore, the present data indicate
      that: i) Free-choice models may reveal the presence of individual sensitivity to
      alcohol or cocaine in naive rats; ii) the dopaminergic system is involved within
      the reward state, while peptidergic (CCKergic) activities modulate the drug
      seeking state (craving state); iii) the CCK system could be a new target in the
      study of the drug dependency phenomenon. In particular, the data imply a CCK-A
      receptor mechanism in the regulation of individual sensitivity towards ethanol
      and a CCK-B receptor mechanism in the regulation of individual sensitivity
      towards cocaine. Thus, a potential therapeutic role for CCK-A antagonists in the
      treatment of ethanol abuse and for CCK-B antagonists in the treatment of cocaine
      abuse is proposed.

PMID- 9922985
TI  - 1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from
      patients with renal insufficiency.
AB  - A reduced expression of the vitamin D receptor (VDR) in parathyroid glands of
      uremic animals and humans has been observed. Similar results have been obtained
      by our own group in peripheral blood mononuclear cells (PBMC) from patients with
      secondary hyperparathyroidism to chronic renal failure. However, the reasons for
      these changes are not clear. In the present study, we have investigated the
      specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic
      renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF),
      and 23 healthy women. The mean dissociation constant (KD) was similar in both
      groups of patients and in healthy women (A-CRF: 0.7 +/- 0.5 x 10(-10) M; M-CRF:
      1.1 +/- 0.9 x 10(-10) M; controls: 1.0 +/- 0.6 x 10(-10) M). However, VDR
      concentration was significantly decreased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells
      vs. 2.3 +/- 0.9 fmol/10(7) cells in controls, p < 0.001), whereas no changes were
      seen in M-CRF (1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in
      controls). No correlation was seen between VDR and serum calcitriol or PTH
      levels, when considering both groups of patients together or separately.
      Conversely, a significant negative correlation was found between VDR and serum
      creatinine values when A-CRF and M-CRF were considered altogether (r = -0.63; p <
      0.01). Treatment with two different schedules of oral calcitriol (five patients
      with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7
      days) did not change VDR concentrations. We conclude that the low levels of serum
      1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration
      found in these patients.

PMID- 9922986
TI  - Expression of CD44 variant isoforms in leukocytes of the joint fluid of
      rheumatoid arthritis patients and the effect of steroids.
AB  - Several CD44 variant isoforms have been reported in the synovium of patients with
      rheumatoid arthritis (RA), but the physiological and pathological roles of these
      isoforms have not been identified. In this study, we investigated the expression
      of CD44 variant isoform mRNA using the reverse transcription-polymerase chain
      reaction (RT-PCR) and TaqMan PCR methods in leukocytes of blood and joint fluid
      obtained from the knee joints of 20 RA patients. We also examined the effects of
      steroids (prednisolone and/or dexamethasone palmitate) and some disease-modifying
      antirheumatic drugs (DMARDs) on the expressions of CD44 variants. The expressions
      of CD44H mRNA and CD44V10 mRNA of leukocytes were significantly higher in both
      the blood and joint fluid samples of the RA patients compared with the samples of
      healthy volunteers. The level of CD44V10 mRNA in the leukocytes of the joint
      fluid was higher than that in the blood of the RA patients. These results suggest
      that the increase of CD44V10 mRNA expression in the leukocytes of RA patients can
      induce a focusing of leukocytes on synovial tissue and an infiltration of
      leukocytes into the joint fluid. In the steroid-treated RA patients, the
      expression of CD44H mRNA in the leukocytes was significantly decreased in the
      joint fluid samples, whereas the expression of CD44V10 mRNA of leukocytes was a
      higher level. None of the DMARDs used here showed any influence on the
      expressions of CD44 variants. These results suggest that steroid treatment
      affects CD44H mRNA expression, whereas steroids and DMARDs have no influence on
      CD44V10 mRNA expression. Therefore, only the suppression of CD44H mRNA expression
      will not be enough to control RA. It is possible that the expression of CD44V10
      is associated with a pathway of RA immunological processes.

PMID- 9922987
TI  - Comparison of present pain intensity assessments on horizontally and vertically
      oriented visual analogue scales.
AB  - Contrary results have been reported from studies comparing horizontal and
      vertical orientations of the visual analogue scale (VAS) in non-dental pain
      states. The vertical orientation of the VAS has been used in our department for
      several years while the horizontal orientation is the most commonly used in other
      acute pain models. The present study investigated whether a horizontally oriented
      VAS is as sensitive as a vertically oriented VAS in the assessment of present
      pain after oral surgery. Seventy-four patients recorded their pain intensity
      hourly and half-hourly 15 times during 11 hours after surgery on a horizontal and
      on a vertical 100 mm VAS. Slightly lower mean and median values were observed at
      2/3 of the observation time points for the vertical VAS compared to the
      horizontal VAS. The results from the two scales were compared with analysis of
      variance for repeated measures. No significant differences between the horizontal
      and the vertical VAS-values were found (p = 0.099). Distributions (Kolmogorov
      Smirnov test) and dispersions of data were also similar with the two orientations
      of the VAS. This study shows that a vertically oriented VAS is equally sensitive
      as a horizontally oriented VAS in assessing present pain intensity after oral
      surgery.

PMID- 9922988
TI  - Cognitive implications for H3 and 5-HT3 receptor modulation of cortical
      cholinergic function: a parallel story.
AB  - Evidence reviewed in this paper suggests that interactions of histamine with H3
      receptors decrease the cholinergic tone in the frontal cortex and the
      hippocampus. These interactions may be important in learning and memory. Both H3
      and 5-HT3 receptors represent targets for pharmacological intervention by
      exogenous compounds acting as antagonists. Thus, the use of compounds with such
      properties as either thioperamide (H3 receptor antagonist) or ondansetron (5-HT3
      antagonist) may represent a potential therapy to correct the deficits resulting
      from cholinergic hypofunction.

PMID- 9922989
TI  - [HLA-B27 molecular subtypes and spondylarthropathies].
AB  - The close association between HLA-B27 and spondyloarthropathies remains
      unexplained. Twelve HLA-B27 subtypes designated B*2701 to B*2712 have been
      described in various populations. Variations in the ability of these alleles to
      carry susceptibility to spondyloarthropathies may exist, and may be ascribable to
      differences in endogenous peptide presentation. This hypothesis was evaluated by
      a study of peptide-binding motifs of endogenous peptides extracted from various
      HLA-B27 alleles. A peptide motif with a tyrosine residue at the C-terminus was
      not characteristic of HLA-B27 subtypes carrying susceptibility, consistent with
      the known lack of association of B*2707 with spondyloarthropathies. However, at
      the level of the individual, differences may exist between endogenous peptides
      presented by subtypes that do and do not confer susceptibility.

PMID- 9922990
TI  - [Specific features of nosocomial infections in the elderly at a general hospital
      center. 5 surveys of annual prevalence].
AB  - Specific features of nosocomial infections in patients aged 70 years or older
      admitted to a short-term care medical department in a 400-bed general hospital
      were studied to assist in designing nosocomial infection control programs for
      this population. Data from five annual prevalence surveys were evaluated
      retrospectively. The 517 patients aged 70 years or older were compared to the
      1093 patients younger than 70 years. The older patients were more likely to have
      risk factors for nosocomial infections including severe disease (36.2% vs 19.1%;
      P < 10(-6)), referral from another department (24.6% vs 17.5%; P < 0.01), a long
      hospital stay duration (8.5 days vs 3.5 days), mechanical ventilation (4.3% vs
      1.6%; P < 0.01), an indwelling urinary catheter (12.0% vs 4.0%; P < 10(-7)), and
      a long median duration of urinary catheterization (6 days vs 2 days). The
      prevalence of nosocomial infections was increased nearly two-fold in the older
      patients (10.3% vs 5.6%; P < 0.01), although the difference was statistically
      significant only for urinary tract infections (5.4% vs 1.4%; P < 10(-5)),
      particularly in patients without urinary catheters. After exclusion of all
      patients with urinary tract infections, the prevalence of nosocomial infections
      was similar in the older and younger patients (4.3% vs 3.7%) despite a
      persistently higher frequency of risk factors for nosocomial infection in the
      older group. These results indicate that urinary tract infection should be the
      main target of programs aimed at minimizing nosocomial infection in elderly
      patients admitted to short-term care facilities. Faultless technique is essential
      during urinary catheter insertion. High-quality nursing care contributes
      substantially to the prevention of urinary tract infection in noncatheterized
      patients with urinary incontinence or neurologic disorders.

PMID- 9922991
TI  - [Epidemiology of sinusitis seen in hospitalized patients. Apropos of 77 episodes
      of sinusitis among 72 patients between 1993 and 1996].
AB  - The 77 cases of sinusitis seen in 72 patients admitted to the Briancon Hospital
      between January 1, 1993, and June 30, 1996, were studied. One or both maxillary
      sinuses were involved in 96.8% of cases. Sinus aspiration was done in 95 cases.
      All aspirates were subjected to microbiological studies. Of the 45 aspirates that
      yielded positive cultures, 36 grew one or more pathogenic organisms. The most
      commonly isolated bacteria were Pseudomonas aeruginosa (n = 7), Streptococcus
      pneumoniae (n = 5), and Haemophilus influenzae (n = 5). Nosocomial sinusitis
      defined on a set of criteria including hospital stay duration at onset and an
      acute tempo of evolution contributed 32.5% of cases overall, 55.2% in the
      intensive care unit and 18.7% in all other departments combined. Nosocomial cases
      in the intensive care unit were associated with well-known risk factors, namely
      tracheal intubation with ventilation and presence of a nasogastric tube. Other
      study criteria included the type of organism recovered by culture and whether
      patients ventilated via a tracheal tube had the same organism in their sinus and
      tracheal tube aspirates. Some nonintensive care patients had none of the known
      risk factors for sinusitis; prompt diagnosis and treatment of these cases of
      sinusitis is important to avoid infectious complications, which are, however,
      less common than in intensive care patients.

PMID- 9922992
TI  - Ethanol interactions with other cytochrome P450 substrates including drugs,
      xenobiotics, and carcinogens.
AB  - Chronic ethanol abuse is associated with increased activity of the microsomal
      ethanol-oxidizing system. This effect is due primarily to induction by ethanol of
      a specific cytochrome P450 (CYP2E1) responsible for enhanced oxidation of ethanol
      and other P450 substrates and, consequently, for metabolic tolerance to these
      substances. Furthermore, cytochrome 450 induction increases the activation of
      numerous xenobiotics to toxic metabolites and of chemical carcinogens to reactive
      metabolites, thereby accelerating their adverse effects. Microsomal enzyme
      induction has been associated with increased reactive oxygen species production
      and enhanced lipid peroxidation, as well as with decreased enzymatic and
      nonenzymatic scavenger activity, providing another possible explanation for
      ethanol-mediated toxicity. Yet another effect of chronic alcohol abuse is chronic
      immune system activation, which is the mechanism underlying alcohol-related liver
      disease. The metabolism of steroids and vitamins is catalyzed by P450 and is
      altered in chronic alcoholics. This article reviews recent advances in the
      understanding of ethanol interactions with drugs, toxic agents, and carcinogens,
      as well as with steroids and vitamins.

PMID- 9922993
TI  - [Tumor antigens recognized by T-lymphocytes in human cancers. New advances and
      therapeutic perspectives].
AB  - The melanoma antigen coded by the MAGE-1 gene was the first tumor antigen
      described in human cancer. Genetic, biochemical, and "candidate peptide"
      strategies have been used to identify antigenic peptides presented to T-cells by
      class I major histocompatibility complex antigens. Antigens have now been
      characterized in a wide variety of tumor types. Five categories have been
      described based on expression profile. These antigens are detailed in this
      review. Among the tumor antigens produced as a result of intratumoral mutations,
      some are of special interest because of their potentially oncogenic effects.
      These new data can be expected to lead to the development of novel anticancer
      treatments based on specific immunotherapy. Pilot clinical studies are ongoing.

PMID- 9922995
TI  - Detection of benzo[a]pyrene-DNA adducts from leukocytes from heavy smokers.
AB  - Benzo[a]pyrene is a cigarette smoke component that is metabolized in the human
      body to the diol-epoxide derivative benzo[a]pyrene-trans- 7,8-dihydrodiol-9,10
      epoxide (BPDE-I), which is the final carcinogen. BPDE-I binds covalently to DNA,
      producing BPDE-I-DNA adducts. A competitive immunoenzymetric assay was used to
      measure BPDE-I-DNA adducts in blood samples from 58 heavy smokers, 32 men and 26
      women, attending a smoking cessation clinic. Cigarette consumption was evaluated
      based on urinary continine levels. None of the subjects worked in jobs involving
      exposure to polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene).
      Concentrations of BPDE-I-DNA adducts varied with cigarette consumption, ranging
      from 10.00 to 28.20 fmol/50 micrograms of DNA.

PMID- 9922994
TI  - Kidney ectopeptidases. Structure, functions and clinical significance.
AB  - Kidney ectopeptidases play an important role in the metabolism of different
      peptides. They activate precursor proteins or inactivate peptides including
      hormones, cytokines, vasoactive peptides (angiotensin II, endothelin),
      neuroendocrine hormones, changing local concentration in active peptides. Kidney
      ectopeptidase regulate cell proliferation, adhesion, matrix synthesis, cell
      signaling, cell activation, differentiation and cell-cell communication. The role
      of four major ectopeptidases (aminopeptidase A and N, dipeptidylpeptidase IV, and
      neutral endopeptidase) is presented.

PMID- 9922996
TI  - [Activated protein C resistance in Behcet disease].
AB  - Behcet's disease is a systemic condition of unknown cause characterized in 20 to
      40% of cases by venous and/or arterial thrombosis that is not fully explained by
      the hemostasis disorders reported in the literature. The present study
      investigated resistance to activated protein C in 65 Behcet's disease patients,
      75 normal subjects, and 70 patients with a history of isolated thrombosis. The
      test used involved predilution in factor V-deficient plasma. Activated protein C
      resistance was found in six Behcet's disease patients (9.2%), eight normal
      subjects (10.6%), and 21 patients with isolated thrombosis (30%). Of the 26
      Behcet's disease patients (40%) with a history of thrombosis, only one had
      activated protein C resistance. Activated protein C resistance does not explain
      the increased risk of thrombosis in Behcet's disease patients.

PMID- 9922998
TI  - [Acute articular rheumatism in the child in 1997].
AB  - Nine cases of rheumatic fever were seen from 1982 to 1996. The diagnosis was
      based on Jones criteria. Four of eight children had carditis characterized by
      mitral regurgitation with or without aortic regurgitation and/or atrioventricular
      conduction disturbances. The outcome was favorable in all the patients who had
      carditis initially; one of the patients without initial carditis developed
      permanent cardiac lesions during a recurrence with carditis. In industrialized
      countries, the incidence of rheumatic fever declined starting early in the XXth
      century, then dropped sharply after World War II, and is now extraordinarily low
      (mean annual incidence, 0.5/100,000 schoolage children). In developing countries,
      by contrast, rheumatic fever was recognized only after World War II and remains
      endemic (mean annual incidence, 100 to 200/100,000 schoolage children),
      contributing a substantial proportion of cases of cardiovascular disease. The
      diagnosis is difficult and rests on clinical grounds since there is no specific
      laboratory test. Diagnostic delays are potentially serious. Acute attacks should
      be managed as therapeutic emergencies. Prevention of recurrences rests on long
      term antimicrobial therapy. Rheumatic fever is a disease process resulting from
      an inappropriate immune response to pharyngitis due to a beta-hemolytic group A
      streptotoccus (BHAS). A low standard of living may be a factor in developing
      countries but fails to explain the epidemic flares seen in these areas or the
      residual background incidence in industrialized countries. A role of host-related
      susceptibility to the disease has not been demonstrated. The type-specific
      surface M protein, the main factor associated with high virulence, carries a
      specific epitope on its distal portion. Rheumatogenic strains have been
      identified; most produce mucoid colonies. At a given point in time, within a
      given serotype, the virulence of a specific strain increases. Temporal and
      spatial variations of observed types contribute additional complexity. Adhesion
      of the organisms is followed by release of streptococcal degradation products
      that share antigenic determinants with human tissues including the heart, the
      synovium, and the neurons. The hyaluronate capsule and M protein of the organisms
      are capable of initiating immune responses; their presentation to CD4+ T-cells
      results in lymphokine production, an acute phase humoral response, and a cell
      mediated response potentially responsible for permanent valvular damage. In
      France, the standard of care is to prescribe antimicrobial therapy to all
      patients with pharyngitis or tonsillitis without performing tests to identify the
      causative agent. The introduction of tests for the rapid recognition in routine
      clinical practice of BHAS, which account for only 20 to 30% of all cases of
      pharyngitis and tonsillitis, should allow a more rational approach to the
      treatment of these infections. Reserving antimicrobial therapy to those patients
      with BHAS should not result in an increase in the incidence or rheumatic fever.

PMID- 9922997
TI  - [Cadherins, the development and regeneration of the neuromuscular axis].
AB  - Various cell adhesion molecules of the cadherin family characterize the
      neuromuscular system. During development, cadherins N and M are sequentially
      expressed by myogenic cells during the two waves of myoblast fusion. Two other
      cadherins, called 6 and 11, are also expressed during the embryonic musculature
      development. In adult muscle, cadherins N and M, whose expression is suppressed
      by muscle activity, persist only at the neuromuscular junction and are
      reexpressed at the surface of denervated fibers. Cadherins N, M and E are also
      expressed in adult peripheral nerves. Their differential localization at Schmidt
      Lanterman clefts, Ranvier nodes and neuromuscular junctions suggest that these
      molecules contribute to the stabilization of specialized intercellular contacts.
      In conclusion, a combination of cadherins, the expression of which is spatially
      and temporally regulated, participates in the differentiation and maintenance of
      the organization of the various cellular and tissular components of the
      neuromuscular system.

PMID- 9923000
TI  - [VIDAS Stallertest: clinico-biological evaluation of a new global test for
      respiratory allergy].
AB  - "VIDAS Stallertest" is a new screening test for breathing allergy. It allows the
      detection of 10 different lung specific allergens including domestic acarids
      (D1), pollents (G3, W6, W21, T3 and T9), pets dander (E1 and E2), moulds (M6),
      cockroach (16). The method is an immunoenzymatic reaction that contains a
      cartridge and a cone that is cover with the allergen's mixture and is automated
      on the VIDAS system. The results are compared to various skin tests analyzed by
      instantaneous reading for 102 patients. "VIDAS Stallertest" shows an excellent
      agreement (93%) with the allergic patients as well as with those that are not.
      The specificity of the new screening test is very high (91%). A comparative study
      between "VIDAS Stallertest" and "Phadiatop" performed on 155 consultants in
      allergist office shows a correlation of 93%, a sensitivity and a specificity of
      91 and 95%, respectively. "VIDAS Stallertest" is a reliable method in first
      intention for the general practitioner who faces a putative breathing allergy.
      Moreover, this is an excellent biological check-up for a questionable or negative
      skin test.

PMID- 9922999
TI  - [Direct diagnosis of Chlamydia trachomatis genital infections: culture or PCR?].
AB  - PCR and culturing were compared for the routine diagnosis of Chlamydia
      trachomatis infections. Two laboratories experienced in both techniques
      participated in the study, which included 513 specimens. Both techniques were
      performed on each specimen; the portion of the specimen used for PCR was divided
      in two, and each half was sent to one of the two laboratories, where the tests
      were run in a blinded fashion. The PCR primers used by the two laboratories
      matched different parts of the bacterial genome. PCR inhibitors were looked for
      in all specimens. Overall, PCR was more sensitive than culturing; the difference
      was marked for sperm and endopelvic specimens and nonsignificant for urethral and
      cervical specimens. False-positive PCR results were few in number; there were no
      consistent false-positive results when each specimen was amplified twice. PCR
      inhibitors were rarely present in urethral and cervical specimens but were found
      in 7% of sperm and endopelvic specimens. PCR inhibitors should be looked for
      routinely during PCR testing of sperm or endopelvic specimens.

PMID- 9923001
TI  - Effects of photoperiod and feeding level on perirenal adipose tissue metabolic
      activity and leptin synthesis in the ovariectomized ewe.
AB  - Leptin is secreted by adipose tissue and plays a pivotal role in regulating both
      body energy homeostasis and reproductive function in rodents. Among livestock,
      sheep is a seasonal breeder whose reproductive period is initiated by short
      daylength. We show that plasma leptin and leptin gene expression in perirenal
      adipose tissue were decreased when ovariectomized Lacaune ewes were exposed to
      short days (8 versus 16 h light/d). This effect of the photoperiod occurred
      despite the nutritional status, with leptin levels lower in underfed than in
      refed ewes, and without significant changes in perirenal fat mass and adipocyte
      size. Plasma prolactin and leptin followed a similar pattern suggesting a
      relationship between the two hormones. These findings indicate, for the first
      time, that adipose tissue leptin is modulated by daylength independently of food
      intake, body fatness and gonadal activity. Furthermore, plasma non-esterified
      fatty acids of underfed ewes subjected to short days were more elevated than for
      underfed ewes on long days. On the other hand, refed ewes placed under long
      daylength tended to have a higher adipose tissue lipogenic activity than refed
      ewes on short days. We propose that these adaptations of leptin production and
      lipogenic activity with long photoperiod are of physiological significance for
      body fat deposition, which naturally occurs during long days when food is
      abundant. Conversely, a low leptin level during short days may enhance the
      sensitivity to food deprivation during the natural reproductive season, where any
      food shortage would decrease plasma leptin under a threshold critical for
      reproduction. Furthermore, in this situation, the observed enhanced ability to
      mobilize body fat may be related to the necessity to cope with energy shortage.

PMID- 9923003
TI  - Differences between blood and plasma concentrations of acetate, beta
      hydroxybutyrate, glucose, ammonia and urea: implications for measurement of
      portal net fluxes in ewes.
AB  - The aim of this study was to determine the differences in concentrations of
      various metabolites between blood and plasma, and their implications for the
      measurement of portal net fluxes in ewes. A wide range of concentrations of
      metabolites in arterial and portal blood was induced by submitting three ewes to
      three different levels of intake. Plasma measurements underestimated the portal
      drained viscera net flux for acetate, glucose, ammonia and urea but not for beta
      hydroxybutyrate. The underestimation of net release was low and largely constant
      for acetate (7%). The net flux of glucose tended to be overestimated by plasma
      measurements when it was low, but was underestimated by 25% when high net uptake
      occurred. The underestimation of net fluxes of ammonia and urea increased with
      their magnitude, up to 17% for ammonia release and 41% for urea uptake.

PMID- 9923002
TI  - Effects of maternal ageing and dietary antioxidant supplementation on ovulation,
      fertilisation and embryo development in vitro in the mouse.
AB  - The present study aims to ascertain whether dietary supplementation with a
      mixture of vitamins C and E may prevent the maternal-age-associated decrease in
      both the number of ovulated oocytes after exogenous ovarian stimulation and
      embryo development in vitro in the mouse. Experimental females were fed a
      standard diet supplemented with i) high doses of vitamins C and E from the first
      day of weaning until 12 or 40 weeks of age; or ii) moderate doses of vitamins C
      and E from the first day of weaning until 12 weeks of age or from 22 to 33 weeks
      of age. The age-related reduction in ovulation rate was partially prevented by
      supplementing diet with high doses of vitamins C and E from the first day of
      weaning. Shorter periods of treatment and lower doses of vitamins C and E were
      also efficient in preventing the maternal-age-associated reduction in ovulation
      rate after exogenous ovarian stimulation. No effect of maternal diet on
      fertilisation and embryo development was observed until the blastocyst stage.
      Although any extrapolation to human fertility should be made with caution, these
      findings may have direct implications for preventing or delaying maternal-age
      associated infertility in humans.

PMID- 9923004
TI  - A method for a selective local application of radioactive precursors of nucleic
      acids to the cow ovary.
AB  - Local application of /5-3H/uridine or /6-3H/thymidine to the cow ovary was
      obtained by the instillation of the radioactive solution into a rubber balloon
      ('bursa') tightly enclosing the organ exposed by laparotomy. After 30-90 min the
      exteriorized ovary was replaced in the abdominal cavity. Ovaries were recovered 1
      8 days later and processed for autoradiography. After /5-3H/uridine application
      the peripheral layer of the ovary, containing the follicles in different stages
      of development was most intensely labelled. The labelling by /5-3H/uridine could
      be attributed prevailingly to the cytoplasm of different cells constituting the
      ovary but in some cases the labelling was higher in nuclei. The highest level of
      labelling was seen in the cytoplasm of follicular cells of follicles composed of
      one or two layers of cuboidal cells. Labelling was also detected in the ooplasm
      of oocytes with the maximal number of grains being seen in the first phase of
      their growth. On the other hand, no labelling was detected in the ooplasm of
      oocytes isolated from antral follicles the growth of which had been induced
      previously by hormonal treatment. It is believed that the labelling obtained by
      the described procedure represents to a significant degree RNA. A similar local
      application of /6-3H/thymidine allowed us to obtain labelling restricted
      specifically to nuclei of different cells composing the ovarian tissue. In the
      presented results, the entry of flattened follicular cells of primordial
      follicles in vivo in the S-phase of the cell cycle was demonstrated as well as an
      evident different proliferation rate in the successive stages of follicle
      development. The method proposed here may probably be the way for testing the
      effects of different substances, available only in small quantities, on the cow
      ovary.

PMID- 9923005
TI  - Influence of nutrition on testicular growth in Corriedale rams during spring.
AB  - To study the effect of nutrition on spring testicular growth, four adult
      Corriedale rams were allowed to graze enough to maintain weight (maintenance
      group), while another four rams, in addition to forage, received a supplemental
      grain-based ration (increased gradually from 100 to 400 g during the first 5 d
      and kept at 400 g thereafter) daily for 63 d (supplemented group). Body weight,
      scrotal circumference, inguinal hyperaemia and testicular consistency were
      assessed. Blood concentrations of LH and testosterone were measured for 24 h on
      the day before supplementation began, the day after the animals were fed 200 and
      400 g, and 12 and 28 d after animals began to receive the supplement. On these
      occasions blood contents of non-esterified free fatty acid and beta
      hydroxybutyrate were measured when animals were fasting. Supplemented feeding
      increased body weight within 21 d and scrotal circumference within 35 d (P <
      0.01). Scrotal circumference also increased in rams of the maintenance group (P <
      0.01) but a lower rate than the supplemented group (P < 0.001). In both groups,
      testicular consistency and inguinal hyperaemia increased (P < 0.01). In the
      supplemented group a transient increase (P < 0.01) in LH pulsatility occurred the
      day after rams had received the full supplement (400 g) and 5 d later (day 12).
      However, no difference was found in total testosterone release between groups. In
      conclusion, improved nutrition accelerated the testicular growth in spring,
      although only a transient increase in LH pulsatility was observed. The scrotal
      circumference of rams kept on maintenance diet did also increase, which indicates
      that nutrition is not the only environmental cue responsible for the vernal
      testicular redevelopment in Corriedale rams.

PMID- 9923007
TI  - Reproductive and productive performance in Chios ewes mated in spring or in
      autumn.
AB  - One hundred and sixty adult ewes of the Chios breed were divided randomly into
      two groups. One group was used for breeding in spring (S) and the other in autumn
      (A). In both groups oestrous behaviour was detected once a day. Ovulatory
      activity, 7 d after oestrus, fertility, prolificacy, embryo mortality, birth
      weight of lambs and milk production were recorded. The percentage of ewes which
      exhibited oestrous behaviour was 92 and 100% in S and A groups, respectively,
      while fertility of mated ewes was 98 and 100%. Ovulation rate was significantly
      lower in S than in A ewes (M +/- sd; 2.85 +/- 1.07 versus 3.44 +/- 1.45,
      respectively, P < 0.0001). However, prolificacy did not differ between the two
      groups (2.04 +/- 0.77 versus 2.13 +/- 0.85, for S and A ewes, respectively) as it
      did not increase after an ovulation rate of 4.0. There were no differences in
      birth weights (except for triplets) but total milk production was significantly
      higher in S ewes (257.5 +/- 100.7 kg versus 153.0 +/- 51.9 kg, for S and A,
      respectively, P < 0.001). These results suggest that despite a higher ovulation
      rate in autumn, higher embryonic mortality at this time of the year leads to
      equivalent fertility, prolificacy and birth weight in spring as in autumn.

PMID- 9923006
TI  - Ram lambs need FSH for normal testicular growth, Sertoli cell numbers and onset
      of spermatogenesis.
AB  - The effect of FSH on the development of the testis in the ram lamb was examined
      in two experiments where lambs were passively immunized against ovine beta-FSH
      from birth until 100 or 160 d. In both experiments, immunization resulted in a
      slower testicular growth relative to that of controls. This effect became
      apparent at around the start of the period of rapid testicular growth (60-70 d of
      age) and resulted in testicular weights at the end of treatment ranging from 37
      to 51% of those of control groups. Within the testis, this was reflected in
      shorter seminiferous tubules (48-64% of controls) and in lower numbers of Sertoli
      cells per testis (57-82%). In the rams immunized until 160 d of age,
      spermatogenesis had begun and immunization against FSH provoked a lower
      production of germinal cells which was not solely due to the lower number of
      Sertoli cells but also due to fewer germinal cells being supported by each
      Sertoli cell. However, the numbers of A0 spermatogonia per testis and the daily
      production of the A1 spermatogonia were unaffected by immunization, but the
      production of the B2 spermatogonia and, as a consequence, of leptotene and
      pachytene spermatocytes and of round spermatids were all markedly lower (43-47%
      of controls). These effects were not due to any decreases in the secretion of LH
      or testosterone as seen in the blood levels of these two hormones. These results
      show that, in the ram lamb, FSH is essential for normal testicular development
      and for the establishment of a normal population of Sertoli cells. They also
      confirm that, once spermatogenesis is established, FSH is necessary for a normal
      production of germinal cells, with one or more of the divisions between the A1
      and B2 spermatogonia being sensitive to suppression of FSH.

PMID- 9923008
TI  - Effect of stabilising amino acids on the digestive absorption of heme and non
      heme iron.
AB  - We used the Ussing chamber model to study heme iron absorption by rat duodenal
      mucosa. Heme iron was obtained by enzymic digestion of bovine haemoglobin and
      concentration of heme (HPH). Its uptake and mucosal transfer was compared to iron
      gluconate (Gluc), at 100 microM and 1 mM. At 100 microM iron uptake (Qtot),
      mucosal retention (Qm) and transfer across the mucosa (Qs) was similar for the
      two sources of iron. Qs was significantly higher at 1 mM for Gluc but not for
      HPH, and was associated with higher levels of Qm. Addition of L-histidine did not
      improve iron absorption and indeed it decreased it if iron was provided as Gluc.
      L-cysteine increased the transfer of iron of both sources. In the in vitro model
      using rat digestive mucosa, heme iron appeared to be an efficiently used source
      of iron, which might prevent its accumulation by gut when supplied in excess.

PMID- 9923009
TI  - In vitro study of molecular weight, hydrophobicity and amino acid composition of
      peptides during breakdown of a casein hydrolysate by two strains of Prevotella
      ruminicola.
AB  - The molecular weight, amino acid composition and hydrophobicity of the peptide
      residue produced by hydrolysis of protein by two strains of Prevotella ruminicola
      (23 and S17/3) were determined. These last two characteristics could play a role
      in the control of proteolysis. Both strains produced dipeptidyl peptidases (DAP
      1) but only P. ruminicola 23 synthesised alanine aminopeptidase. The area of 3-5
      kDa peptides decreased, while the peptides directly assimilable by bacteria (0.5
      1 kDa and < 0.5 kDa) increased with strain S17/3, but decreased with P.
      ruminicola 23. The amino acid compositions showed that the proportions of these
      compounds changed little with time and there was proline enrichment. Similarly,
      reverse phase HPLC showed no evidence of enrichment of the culture medium by
      hydrophobic peptides during the growth phase of P. ruminicola. These experiments
      show that the changes in the various peptide classes resulting from the
      hydrolysis and uptake of peptides by P. ruminicola differed with time and
      depended on the strain used. The nature of the enzyme activity and the use of
      other nitrogen sources may explain the difference between the two strains.

PMID- 9923010
TI  - Consequences of ddI-induced reduction of acute SIVmac251 virus load on cytokine
      profiles in cynomolgus macaques.
AB  - This study evaluates the consequences of antiretroviral treatment of the acute
      simian immunodeficiency virus (SIV) primary infection on virus load and cytokine
      responses. Four cynomolgus macaques were inoculated intravenously with a
      pathogenic primary isolate (SIVmac251). Animals were pretreated with 10.8
      mg/kg/day of dideoxyinosine (ddI) from 4 days before inoculation, and treatment
      was continued for 28 days. Proinflammatory (IL6, IL1 beta and TNF alpha) and
      antiinflammatory (IL10) cytokine and lymphokine (IL2, IL4 and IFN gamma)
      polymerase chain reaction (PCR) ratios were monitored in unmanipulated peripheral
      blood mononuclear cells (PBMCs) during acute infection by using a
      semiquantitative reverse transcription (RT)-PCR method. PBMC-associated virus
      loads were dramatically reduced compared to those of placebo-treated macaques.
      Nevertheless, a transient rise in IL6, IL1 beta, TNF alpha and IL10 mRNA
      expression was observed in PBMCs. IL2, IL4 and IFN gamma mRNAs were either
      undetectable or weakly detectable throughout the study, with no major changes.
      Despite a dramatic reduction in the acute viral loads in ddI-treated monkeys,
      early cytokine mRNA profiles were comparable to those of untreated SIVmac251
      infected monkeys. Contrary to what was previously evidenced during primary
      infection with an attenuated SIV clone, no increase in IL2 and IL4 mRNA was
      detected in PBMCs of the ddI-treated monkeys, although these monkeys exhibited
      virus loads similar to those evidenced in macaques infected by attenuated SIV.
      These data indicate that differential lymphokine expression patterns found in
      pathogenic and Nef-truncated SIV-infected monkeys may not be strictly dependent
      on virus load levels.

PMID- 9923011
TI  - Mutations in the human immunodeficiency virus type 1 reverse transcriptase gene
      observed in stavudine and didanosine strains obtained by in vitro passages.
AB  - We have selected a human immunodeficiency virus type 1 (HIV1) using the technique
      of in vitro selection to generate variants that are resistant to didanosine
      and/or stavudine. After serial passages of the Lai strain of HIV1 in MT-2 cells
      in increased concentrations of didanosine-stavudine association, 2 novel
      mutations in reverse transcriptase at codon 57 (Asp-->His) and at codon 98 (AIa-
      >Val) were observed. These mutations were associated with an 11.5-fold increase
      in the didanosine and a 4.5-fold increase in the stavudine 50% inhibitory
      concentration.

PMID- 9923012
TI  - Structure/antigenicity relationship of cyclic and linear peptides mimicking the
      V3 loop of HIV2 envelope glycoprotein.
AB  - We report the structure and antigenicity of the third variable region (V3) of the
      HIV2 envelope glycoprotein by the use of linear and cyclic peptides. To this end,
      a peptide mimicking this region was synthesized and purified, both as an
      iodoacetamidated linear peptide and a disulphide-bridged cyclic peptide. The
      cross-reactivity of three monoclonal antibodies (mAbs) produced against the
      envelope glycoprotein gp140 with the linear and cyclic peptides was tested with
      ELISA. The results showed that the cyclic peptide is a better ligand for the 3
      mAbs 125-F, 125-J and 125-K. The avidity of the mAb/peptide interaction was
      further analysed by determining the concentration of linear or cyclic peptide
      leading to 50% inhibition of mAb-peptide complex formation (K0.5). The K0.5 value
      of mAb 125-F, which displayed the best reactivity with gp140, was estimated to be
      5 times higher for the linear (K0.5 = 1.5 x 10(-6) M) than for the cyclic peptide
      (K0.5 = 3 x 10(-7) M). This indicates a higher affinity of mAb 125-F for the
      cyclic peptide. mAb 125-J, which exhibited a lower avidity for the gp140 compared
      to mAb 125-F, had a similar affinity for the cyclic and the linear peptides (K0.5
      = 3 x 10(-7) M). mAb 125-K had the lowest reactivity with gp140 and its binding
      to adsorbed peptide could not be inhibited by the soluble linear or cyclic
      peptide used up to 10(-5) M. These results suggest that cyclic peptides may have
      a higher propensity for adopting a native-like structure for the peptide/antibody
      interaction. Nuclear magnetic resonance experiments at 25 degrees C in phosphate
      buffer pH 5.4, however, showed that neither peptide displayed a well-defined
      structure.

PMID- 9923013
TI  - Evidence that single-stranded DNA wrapped around the tubulofilamentous particles
      termed "nemaviruses" is the genome of the scrapie agent.
AB  - Homogenized brain tissue from scrapie-infected hamsters and uninfected hamsters
      was subjected to subcellular fractionation to isolate unique tubulofilamentous
      particles termed "nemaviruses". Nucleic acid was purified from the concentrate by
      the phenol/chloroform extraction procedure and by alkaline gel electrophoresis; a
      single band of ssDNA corresponding to about 1.2 kb was visualized. The gel
      purified ssDNA was mixed before inoculation with (a) MgCl2, (b) lipofectin, (c)
      ssDNA-binding protein and (d) normal brain homogenate. Hamsters in group b, c and
      d injected with a mixture of ssDNA developed the clinical disease. Brain
      pathology revealed generalized vacuolation, while animals injected with ssDNA
      mixed with MgCl2 and controls remained healthy. These results suggest that ssDNA
      is the genome of the scrapie agent.

PMID- 9923014
TI  - Identification of membrane antigens important for adsorption of human T-cell
      leukaemia virus type I.
AB  - We isolated three monoclonal antibodies (mAbs), H3e, H11b and H16h, which were
      capable of inhibiting syncytium formation induced in a human T-cell line MOLT-4
      or a human glioma line U251 MG by coculture with human T-cell leukaemia virus
      type I (HTLV-I)-positive human T-cell lines. The mAbs partially inhibited the
      plating of pseudotypes of vesicular stomatitis virus (VSV) bearing envelope
      antigens of HTLV-I. Formation of proviral DNA was also inhibited when indicator
      cells were treated with the mAbs before adsorption of HTLV-I, but not after its
      adsorption. They did not inhibit syncytium formation induced by human
      immunodeficiency virus type 1. Flow cytometry revealed that H16h hardly reacted
      with various HTLV-I-positive T cells, while H3e and H11b reacted with HTLV-I
      positive human cells as well as HTLV-I-negative human cells. H11b and H16h
      immunoprecipitated the membrane antigen with a molecular weight of 20 and 110-130
      kDa, respectively. Western blot analysis showed that H3e, H11b and H16h bound to
      the protein of 20, 20 and 110-130 kDa, respectively. Thus, these findings suggest
      that the 20- and 110-130-kDa cell surface proteins may play a role at the early
      stage of HTLV-I infection.

PMID- 9923015
TI  - Study of human foamy virus proviral integration in chronically infected murine
      cells.
AB  - This report describes integration sites of human foamy virus (HFV) in chronically
      infected BALB/c murine cells that we isolated by inverse PCR and characterized.
      We show that integration of HFV proviral genome mainly occurs in highly
      repetitive and/or transcriptionally active regions and leads to the formation of
      a 4-bp cellular direct repeat sequence at each provirus extremity. As non-random
      deletions were previously described in the HFV be/1 transactivator gene as well
      as in the long terminal repeats (LTRs), these regions were verified in integrated
      HFV. The analysis reveals that, in the studied chronic state, the defective
      interfering virus (delta HFV) is the main integrated proviral form and is always
      associated with a small LTR. Our results show that HFV can use a classic
      retroviral integration process to enter the host cell genome and stress the
      importance of delta HFV and the short LTRs in the establishment of the chronic
      state of infection.

PMID- 9923016
TI  - Selection and characterization of two specific monoclonal antibodies directed
      against the two variants of human herpesvirus-6.
AB  - Monoclonal antibodies (mAbs) specific for human herpesvirus-6 (HHV6) proteins
      were derived from the splenocytes of mice immunized with HHV6 TAN isolate
      infected peripheral blood mononuclear cells. The two mAbs 8C8 and 7C7 reacted by
      means of immunofluorescence and immunoperoxidase assays with both variant A and
      variant B isolates giving two different staining patterns. In infected cells,
      cytoplasmic diffuse staining was observed with mAb 8C8, whereas intense nuclear
      staining was obtained with mAb 7C7. These different locations of viral target
      proteins were confirmed by confocal microscopy. The mAb 8C8 reacted with a family
      of six glycoproteins designated as the gp72 complex in the case of variant A
      strains and gp63 complex in the case of variant B strains. The endoglycosidases H
      and F reduced those glycoproteins to a putative precursor molecule of 58 kDa. The
      mAb 7C7 reacted with 116 and 109 kDa proteins with the two HHV6 variants. These
      two mAbs did not neutralize virion infectivity in the absence of complement. No
      cross-reactivity was observed when these mAbs were used in immunoperoxidase assay
      and immunoblotting against the proteins of human cytomegalovirus or other human
      herpesviruses. Thus, the two mAbs 8C8 and 7C7 may be valuable tools for the
      diagnosis and biological investigation of HHV6 infections.

PMID- 9923017
TI  - A recombinant Toscana virus nucleoprotein in a diagnostic immunoblot test system.
AB  - Sandfly fever, a vector-borne disease endemic in the Mediterranean region, is
      caused by Toscana virus (TOS). The disease is increasingly important as a travel
      related infection. Serological diagnosis is currently dependent on viral antigens
      derived from TOS-infected cell cultures. In this study, we report the cloning and
      expression of the TOS nucleoprotein (N) in Escherichia coli and evaluation of the
      recombinant (r) TOS N protein as an antigen for immunoblot assays. The TOS N gene
      was amplified by reverse-transcriptase polymerase chain reaction and cloned into
      the bacterial expression vector pTrcHis-A. Sera with known TOS antibody status
      were used to evaluate the immunoblot assay. The expressed rTOS N protein was
      purified and used as antigen for immunoblots. By recombinant immunoblot, the TOS
      antibody status (IgM and/or IgG) of the test panel was correctly identified. No
      cross-reactivity was detected. The rTOS N protein is useful as an antigen for
      immunoblot assays, and will enable more laboratories to perform TOS antibody
      diagnosis.

PMID- 9923018
TI  - Inducible expression of herpes simplex virus thymidine kinase from a bicistronic
      HIV1 vector.
AB  - The possibility of protecting human CD4+ lymphocytes from human immunodeficiency
      virus type 1 (HIV1) infection, through a suicide mechanism elicited by the HIV1
      transcription apparatus itself, offers a potentially useful approach for gene
      therapy of the acquired immunodeficiency syndrome. A replication-defective
      lentiviral HIV1 vector (HYIRES-TK) was designed to carry both the hygromycin (Hy)
      phosphotransferase gene for positive selection and the thymidine kinase (TK) gene
      of herpes simplex virus driven by the viral long terminal repeat (LTR). The
      internal ribosome entry site (IRES) from encephalomyocarditis virus was placed
      between the two genes for their efficient simultaneous translation. Transient
      expression of active TK into transfected COS-1 cells was shown to be induced by
      Tat and Rev over a detectable basal level. By providing the missing viral
      proteins in trans, recombinant viruses were generated and used to transduce
      Jurkat cells. The Hy-resistant population of cells was sensitive to ganciclovir
      (GCV) and acyclovir (ACV), a result consistent with a basal level of TK
      expression. Cocultivation of transduced cells with cells chronically infected
      with HIV in the presence of 10 microM ACV, a concentration non-toxic for the
      uninfected cells, resulted in increased killing of cells transduced with the HY
      IRES-TK vector. These data indicate that two genes can be expressed from the
      viral LTR in the context of an HIV1 vector, with the aid of an IRES sequence. The
      expression is inducible by the HIV proteins Tat and Rev and it is possible to
      specifically kill infected cells with subtoxic concentrations of drug. To
      decrease the sensitivity of the transduced cells towards GCV, a variant vector
      expressing a truncated TK was constructed. The truncated version was expressed at
      levels similar to those of wild-type TK but induced sensitivity towards GCV in
      transduced cells that was intermediate between that of untransduced cells and of
      cells expressing wild-type TK.

PMID- 9923019
TI  - Prevalence and patterns of HGV/GBV-C infection in patients with suspected HCV
      related hepatitis.
AB  - Hepatitis G virus (HGV) is a recently described hepatotropic parenterally
      transmitted flavivirus. The presence of HGV was tested in 61 patients with a
      request for confirmation of HCV active infection. Thirty-two patients were in
      haemodialysis and 29 were referred from wards other than nephrology. Active HCV
      and HGV infections were determined by detection of their viral RNA in serum.
      Evaluation of previous HGV infection was carried out by detection of antibodies
      to E2 antigen. HCV prevalence was 62.29% (38/61). HGV-active infection was found
      in 11.47% (7/61) of the population studied: in 18.7% (6/32) of the haemodialysed
      patients and in 3.4% (1/29) of patients belonging to the other group. HGV
      prevalence increased two-fold when previous infection was also considered. HGV
      clearance was prospectively detected in 5 out of the 7 patients with active
      infection, and at an earlier stage for those patients coinfected with HCV. Anti
      E2 seropositivity was associated with HGV clearance in only two patients.

PMID- 9923021
TI  - Biological and clinical responses of west African sheep to Crimean-Congo
      haemorrhagic fever virus experimental infection.
AB  - West African sheep appear to play a central role as virus hosts in the
      maintenance cycle of Crimean-Congo haemorrhagic fever (CCHF) virus in endemic
      areas and also because of their role as a principal host of the CCHF virus tick
      vector. In an effort to clarify CCHF epidemiological significance in sheep, we
      studied the biological and clinical aspects of sheep experimentally infected with
      CCHF virus. West African sheep breeds were infected either by intraperitoneal
      inoculation or by infestation with experimentally CCHF-virus-infected ticks
      (Hyalomma truncatum). A total of 17 sheep including controls as well as 5 lambs
      from their progeny were monitored. A moderate but constant fever was observed
      (39.7 degrees C +/- 0.3) which correlates with the viraemia. Virus was reisolated
      from blood samples taken from day 3 to day 9 postinfection (p.i.) at a mean titre
      of 3.3 log LD50/ml. The virus was detected for a period of time of 7 days in non
      immune sheep and for less than 4 days in previously immunized sheep. In non
      immune sheep, antibody detected by ELISA showed an IgM response on day 7 p.i.,
      followed by an IgG response one day later. Five infected sheep, surveyed for
      liver and kidney biological markers, showed hepatic dysfunction with a moderate
      serum aspartate transferase rise to 210 U/l. Out of four sheep tested for blood
      markers, two showed an abnormal blood cell count, with marked neutrophilia of up
      to 63% lasting for two weeks. Infected pregnant ewes produced antibodies in their
      milk at a significant titre (1:1,000), and antibodies were recovered in the sera
      of nursing lambs from their first meal to 50 days after birth. These findings are
      discussed; they demonstrate that, in spite of a high turnover of local sheep
      herds (median age of 3 years) and long-term CCHF antibody persistence (> 3
      years), sheep can be infected and efficiently transmit the virus at least once in
      a lifetime.

PMID- 9923020
TI  - Genetic evolution of the hypervariable region 1 in hepatitis C virus carriers
      with normal aminotransferase activities.

PMID- 9923023
TI  - [Risk factors in severe asthma].
AB  - Risk factors for severe acute asthma involve the patient, the environment and the
      society in general. In addition, there are strong interrelationships between
      these factors. Personal characteristics linked to acute severe asthma include age
      (teenagers), denial leading to poor compliance, depression with atypical symptoms
      in children, and some medical features of asthma associated with increased
      severity. Environmental factors include airborne allergens, infections, irritants
      such as air pollutants and passive smoking. Life events have not been extensively
      studied but are likely to play a predominant role. The social setting,
      particularly the health care system, acts as an interface between the patient and
      the environment. Most all asthma deaths are avoidable and related to dysfunctions
      in the health care system.

PMID- 9923022
TI  - Molecular epidemiology of Malaysian dengue 2 viruses isolated over twenty-five
      years (1968-1993).
AB  - The limited sequencing approach was used to study the molecular epidemiology of
      24 Malaysian dengue 2 viruses which were isolated between 1968 and 1993. The
      sequences of a 240-nucleotide-long region across the envelope/non-structural 1
      protein (E/NS1) gene junction of the isolates were determined and analysed.
      Alignment and comparison of the nucleotide and deduced amino acid sequences of
      the isolates revealed that nucleotide changes occurred mostly at the third
      position of a particular codon and were of the transition (A<-->G, C<-->U) type.
      Five nucleotide changes resulted in amino acid substitutions. Pairwise
      comparisons of the nucleotide sequences gave divergence values ranging from 0 to
      9.2%. At the amino acid level, the divergence ranged between 0 and 3.8%. Based on
      the 6% divergence as the cut-off point for genotypic classification, the isolates
      were grouped into two genotypes, I and II. Comparison of the nucleotide sequences
      of the Malaysian dengue isolates with those of the dengue viruses of other
      regions of the world revealed that members of genotypes I and II were closely
      related to viruses from the Indian Ocean and Western Pacific regions,
      respectively.

PMID- 9923025
TI  - [Respiration and aging].
AB  - Pulmonary aging is a term used to designate age-related alterations in pulmonary
      function. In includes both respiratory functions (ventilatory mechanics, gas
      exchange) and non-respiratory functions (immunity) of the lung. The age-related
      decline in respiratory function is not linear. Generally after 70 years, PaO2 no
      longer declines and, in elderly men, the FEV1/FVC ratio remains stable. Because
      of the wide variability of reference values, caution should be taken in
      interpreting changes in ventilatory mechanics (e.g. spirometry) in elderly
      people.

PMID- 9923024
TI  - [Ozone and the immune system].
AB  - This review focuses on the effect on health of changes in the immune system
      secondary to ozone exposure and on various mechanistic hypotheses put forward.
      Beyond the problems related to the variability of study criteria (e.g. age, sex,
      concentration and duration of different types of exposure, the slightly volatile
      nature of ozone and the complexity of the immune system), ozone may induce
      immunostimulation as shown by intensified allergic phenomena or immunosuppression
      expressed by increased sensitivity to bacterial infections. Different functions
      of the immune response (for example macrophage and polynuclear phagocytic and
      bactericidal activity, NK activity, cytokine and antibody production ...) are
      affected. In terms of risk, the consequences of these changes depend on their
      intensity, their perennial nature and their association with particular genetic
      characteristics or other forms of external aggression, for example infection. The
      effect of exposure to a mixture of pollutants with unknown interactions should
      also be taken into consideration. Finally, the problem of normal but possibly
      exaggerated immune response to a compound whose allergenicity may have been
      modified by ozone must also be taken into account.

PMID- 9923027
TI  - [Diagnosis of nocturnal respiratory disorders. Review of portable monitoring
      devices. Analysis and evaluation of different polysomnography signals].
AB  - Polysomnography in an attended hospital laboratory setting is the gold standard
      for the diagnosis of sleep-related breathing disorders. However, this method is
      expensive and waiting lists are long. Portable recording devices that can be used
      at home have been recently developed to improve upon the problems of
      polysomnography. We review the recent portable devices validated by
      polysomnography and discuss their precise role in the assessment of sleep-related
      respiratory disorders.

PMID- 9923026
TI  - [Asbestos exposure and pleuropulmonary cancer].
AB  - Pleuropulmonary cancers are recognized asbestos-related diseases. Mesothelioma
      occurs almost uniquely in individuals exposed to asbestos whereas lung cancer is
      strongly associated with smoking. If the asbestos exposure is sufficient however,
      the incidence of lung cancer is higher than would be expected from the smoking
      effect alone. For lung cancer in asbestos workers, asbestosis is not a
      prerequisite for recognition as an occupation-related disease. The intensity and
      duration of exposure to asbestos are factors associated with higher risk of lung
      cancer. These factors can be estimated on the basis of the work history or, when
      necessary, by analyzing mineral dust from available lung tissues.

PMID- 9923028
TI  - [Short-duration nocturnal hypoxemia and persistent pulmonary hypertension].
AB  - Can daily short-duration hypoxemia (4-8 hours) induce pulmonary hypertension and
      right ventricular hypertrophy? A clinical model of this type of hypoxemia does
      exist: isolated nocturnal hypoxemia in patients with obstructive sleep apnea
      syndrome (OSAS) or chronic obstructive pulmonary disease (COPD). By investigating
      the pulmonary hemodynamics of these patients, it should be possible to determine
      whether nocturnal hypoxemia alone can induce pulmonary hypertension. Although
      nocturnal hypoxemia (in OSAS as well as in COPD) can induce acute episodes of
      pulmonary hypertension, it would not appear that nocturnal hypoxemia alone would
      be sufficient to provoke permanent diurnal pulmonary hypertension. This is the
      conclusion of recent studies concerning diurnal pulmonary hemodynamics in OSAS
      and COPD patients exhibiting minimal hypoxemia during the day but significant
      nocturnal desaturation. The therapeutic consequences of these data, particularly
      in COPD are important: current evidence is insufficient to treat with nocturnal
      oxygen therapy COPD patients who have minimal diurnal hypoxemia but significant
      nocturnal desaturation.

PMID- 9923029
TI  - [Smoking in professional soccer players in France].
AB  - An enquiry was conducted to determine the smoking habits of coaches and
      professional soccer players in the first and second division of the French
      championship in 1993 and 1994. The rate of response was 31% for coaches (36
      responded) and 54% for players (257 responded). Among the coaches, 19% were
      smokers, 14% were ex-smokers and 67% were non-smokers; for players, the rates
      were 36%, 3% and 71% respectively. The percentage of smokers was higher in second
      division players (31%) than in first division players (20%). Forty percent smoked
      less than 6 cigarettes a day. Fifty-eight percent of the coaches and 39% of the
      players thought that smoking and sports were compatible. This study shows that
      even the highest level sports are not spared from the effect of smoking. Other
      reports of similar smoking habits have been reported in other sports in France.
      The image of athletes who smoke given by the media is in contradiction with the
      national French policy forbidding tobacco advertising in stadiums.

PMID- 9923030
TI  - [Assessment of three filters for respiratory function tests].
AB  - Several filters specific for respiratory function tests have been on the market
      for several years. Recommended by the manufacturers to avoid contaminating the
      equipment and thus improve patient safety, these filters require a considerable
      financial investment. We studied the passage of diluted blood into artificial
      saliva in a patient model simulating inspiration tests and rapid forced
      expiration to assess the retention capacity of three filters used for respiratory
      function tests: Multi SPIRO MI-90016 (MultiSPIRO), PF 30S (Pall Biomedical) and
      Spirobac (Dar. S.p.A). The mean percentage of passage was 1.48% through the MI
      90016 filter, 57.15% through the PF 30 S filter and 70.45% through the Spirobac
      filter. These findings provide further elements for choosing filters for
      respiratory function tests. Indeed, despite the manufacturers' commercial
      arguments, the technical documents provided do not give necessary information on
      the filtering capacity of the filters on the market. We have observed that two
      out of the three filters tested do no meet the standards expected by clinicians.

PMID- 9923032
TI  - [Methodology for assessing continuing medical education at the first united
      French congress of pneumology].
AB  - The evaluation of continuing medical education (CME) courses will soon become one
      of the tools used to assess post-graduate training, particularly in compliance
      with the recent legislation. In 1997, the organization committee of the French
      congress of pneumology decided to analyze the different methodologies used to
      assess the congress CME courses. The analysis was based on a satisfaction
      questionnaire, a before-after assessment of 4 workshops, and a comparison between
      participants and non-participants in 3 plenary sessions. Mann-Whitney and
      Wilcoxon non-parametric tests were used for statistical analysis. Satisfaction
      scores were high. For the plenary sessions, test results were better for
      participants than for the non-participant controls and for the workshops, test
      results were higher after completion. This type of study can only evaluate the
      level of knowledge acquired and is subject to a selection bias. It cannot analyze
      the practical impact of the courses nor their effect on patient health. Such
      assessment methodologies should be used more widely in order to improve future
      training sessions.

PMID- 9923031
TI  - [Respective influence of occupational and personal factors on respiratory
      function in dairy farmers].
AB  - Occupational and individual factors influencing respiratory function were
      analysed in a sample of dairy farmers. The study protocol included a medical
      questionnaire, an occupational questionnaire, spirometry and allergological tests
      (skin prick tests for a panel of inhalant allergens, serum total IgE level and
      Phadiatop (CAP System). Two hundred and forty-five farmers were studied (140 men,
      105 women with an average age of 45.9 (11.3) years, 35 were smokers, 27 ex
      smokers and 183 non-smokers). A multiple linear regression model was used to
      analyse the correlations between respiratory function and the different
      independent variables. There was a statistically significant negative
      correlations between smoking (expressed in pack-years) and all the respiratory
      function parameters (p < 0.01). Respiratory function was significantly impaired
      in farmers working on traditional farms (p < 0.05 for VC and for FEV1), and the
      respiratory function values increased proportionally with the modernisation of
      the farms (notably using an artificial barn drying system for hay and a
      ventilation system for the cow byres). No significant relationship between
      respiratory function and quantitative indicators of exposure (size of farm,
      amount of livestock, quantity of hay handled during professional lifetime) or
      indicators of IgE-mediated allergy was observed. In conclusion, this study
      suggests that traditional work conditions in farms which have little
      mechanisation are, along with tobacco, the determining factors for the
      respiratory function impairment in dairy farmers.

PMID- 9923033
TI  - [Quebec spirometry reference values].
AB  - Lung volumes forced expiratory flow rates and carbon monoxide diffusing capacity
      (apnea) were measured in 397 non-smoking, nonatopic, asymptomatic subjects (219
      women, 178 men). The equipments and methods for measurements met the ATS
      criteria. The linear regression of the different variables according to age and
      height allowed the elaboration of a new set of predictive equations (Quebec).
      When comparing the different reference values used in North America and Europe,
      it is found that those of Miller and associates as well as those recommended by
      the CECA provide the best description of the Quebec situation. However, we would
      eventually prefer the reference values of Miller and associates over those of the
      CECA, because they better fit the current ATS criteria and also provide
      references for smokers. Lung volumes and forced expiratory flow rates of 97 non
      smoking, nonatopic, asymptomatic manual workers were measured in the same
      conditions and submitted to the same comparisons. Quebec predictive values as
      well as those of Miller and associates isolated the same individuals in the so
      called abnormal zone. We therefore conclude that Quebec's standards should be
      preferred in the Province of Quebec pulmonary function laboratories.

PMID- 9923034
TI  - [Management of hemoptysis in invasive pulmonary aspergillosis].
AB  - Invasive pulmonary aspergillosis is an opportunistic infection occurring in a
      background of severe immune depression. The majority of cases occur in patients
      who have malignant hematologic disease, particularly during chemotherapy
      induction or consolidations phases for acute non-lymphocytic leukemia. The
      principal risk factors are profound (PN < 500 per mm3) and prolonged (very high
      risk beyond 20 days) neutropenia, perturbed phagocyte function and cellular
      immune deficiency (AIDS, immunosuppressive treatment in organ and bone marrow
      recipients). Clinically, invasive pulmonary aspergillosis presents as acute non
      specific pneumonia with cough, chest pain and fever. The severe infection rapidly
      becomes life-threatening. The development of massive hemoptysis is a major risk.
      We report four cases of invasive pulmonary aspergillosis in patients who had
      hemoptysis. All four patients developed non-specific pneumonia resistant to broad
      spectrum antibiotics during post-chemotherapy aplasia. Computed tomography of the
      thorax and bronchoscopy with bronchoalveolar lavage was performed due to the
      occurrence of hemoptysis. In the first two cases, the patients were recovering
      from aplasia. The thoracic CT scan showed evidence of a cavitating mass with
      peripheral vessels. Bronchoscopy findings suggested mucosal lesions. The patients
      were managed surgically. Pathology confirmed the diagnosis of invasive pulmonary
      aspergillosis with the presence of ischemic necrosis of the pulmonary parenchyma
      harboring numerous aspergillus filaments. Outcome was favorable and chemotherapy
      was re-initiated in one case. These two patient died from their hematological
      disease a few months later. The other two patients remained in aplasia. A CT of
      the thorax showed multifocal infiltration with vascular contact. Bronchoscopy was
      again suggestive. One patient developed massive hemoptysis with respiratory
      distress. Embolization was performed but the patient died two days after onset of
      hemoptysis. In the last case, embolization was successful and outcome was
      favorable enabling a bone marrow allograft; the patient died a few months later
      from the hematological disease. The potential gravity of hemoptysis in the course
      of invasive pulmonary aspergillosis should lead to early treatment with emergency
      CT scan and, if possible, bronchoscopy with bronchoalveolar lavage to establish
      the therapeutic strategy based on surgical excision or embolization of the
      pulmonary or bronchial arteries.

PMID- 9923035
TI  - [Acute eosinophilic pneumonia due to hypersensitivity to carbamazepine].
AB  - The authors report a case of hypersensitivity to carbamazepine presenting as an
      acute eosinophilic pneumonia and a probable hypersensitivity myopericarditis in a
      54-year-old patient treated with carbamazepine for three weeks. Treatment
      consisted of stopping the carbamazepine and in prolonged corticosteroid therapy.
      The features of the hypersensitivity syndrome to carbamazepine are mentioned as
      well as the different pulmonary disorders attributable to carbamazepine.

PMID- 9923036
TI  - [Similarities between pleuropulmonary blastoma and Askin tumor].
AB  - Adult pleuropulmonary blastoma is an uncommon mesenchymal tumor of the peripheral
      lung parenchyma composed of undifferentiated cells. The differential diagnosis
      with Askin-Rosai's tumor, an extrapulmonary pleuroparietal neuroectodermal tumor,
      may be a difficult task. We propose a similar therapeutic approach for these two
      malignant conditions: surgical excision associated with chemotherapy and
      autologous bone marrow transplant with adjuvant radiotherapy in case of
      recurrence. These two entities have many epidemiological, clinical, histological
      and immunohistochemical similarities.

PMID- 9923037
TI  - [Hypoxic eosinophilic pneumonia in two patients treated with ACE inhibitors].
AB  - Diffuse hypoxic pneumonia was found to be caused by angiotensin converting enzyme
      (ACE) inhibitors in two patients given enalapril and fosinopril for hypertension.
      Both patients developed sub-acute respiratory failure and lost weight. Imaging
      explorations showed multiple areas of alveolar consolidation, moderate pleural
      effusion and in one case linear opacities. In both cases, peripheral eosinophila
      was found and the bronchoalveolar lavage fluid contained lymphocytes. Progressive
      improvement was achieved after withdrawal of the ACE and corticosteroid therapy
      for three months. Subsequent x-rays and respiratory function tests returned to
      normal apart from persistently low CO diffusion in one patient. In view of other
      cases reported in the literature, ACE inhibitors should probably be included in
      the list of drugs capable of inducing pneumonia, notably eosinophilic pneumonia.

PMID- 9923038
TI  - [Hemoptysis in pneumonia].

PMID- 9923040
TI  - The hepatitis C virus and systemic diseases.

PMID- 9923039
TI  - [Diagnosis of drug allergies].

PMID- 9923041
TI  - Quantifying quality of life: overcoming an apparent paradox to meet an urgent
      need.

PMID- 9923042
TI  - Iloprost as cyclic five-day infusions in the treatment of scleroderma. An open
      pilot study in 20 patients treated for one year.
AB  - OBJECTIVE: To evaluate the safety and efficacy of cyclic intravenous iloprost
      therapy in diffuse or limited scleroderma. METHODS: Twenty patients, 14 women and
      6 men with a mean age of 47.8 +/- 8.2 years, were given iloprost infusions for
      six hours a day during five consecutive days, at a rate of 0.5 to 2 ng/kg/min.
      The course was repeated every three months for one year. Efficacy was evaluated
      based on a scleroderma skin lesion score, an ischemic lesion score, a well-being
      self-assessment score, and lung function tests including measurement of the
      diffusing capacity of the lung for carbon monoxide. Safety was assessed based on
      adverse event collection. RESULTS: The scleroderma skin lesion and ischemic
      lesion scores decreased significantly over the one-year treatment period, from
      37.1 +/- 16.5 to 10.2 +/- 6.9 (P < 0.001) and from 31.8 +/- 19.1 to 2.2 +/- 2.0
      (P < 0.05), respectively. The well-being self-assessment score also showed a
      significant improvement, from 71.4 +/- 16.5 to 15.0 +/- 6.6 (P < 0.001). The
      diffusing capacity for carbon monoxide was decreased in 11 patients at baseline
      and showed a slight, non significant increase in these patients after the
      treatment period. No serious or persistent side effects were recorded.
      CONCLUSION: Cyclic intravenous iloprost therapy was associated with improvements
      in skin changes and in general health, as well as with a slight increase in the
      diffusing capacity of the lung for carbon monoxide. Our data suggest that
      iloprost may act on some of the pathogenetic mechanisms of scleroderma in a way
      that improves the course of the disease.

PMID- 9923043
TI  - Comparison of the Health Assessment Questionnaire and Arthritis Impact
      Measurement Scale in patients with psoriatic arthritis.
AB  - OBJECTIVE: To determine which of two instruments, the Health Assessment
      Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS), was more
      closely correlated with the main parameters reflecting activity and severity of
      psoriatic arthritis. METHODS: Both instruments were administered to 72
      consecutive patients with psoriatic arthritis. RESULTS: Global HAQ and AIMS
      scores were closely correlated with each other (rs = 0.747; P < 0.00001). AIMS
      physical function scales--namely physical activity, dexterity, social activity
      and activities of daily living--were moderately or closely correlated with the
      main clinical disease activity parameters, most notably morning stiffness of
      axial joints (rs = 0.271-0.551). Scales measuring psychological status yielded
      weaker correlations with disease activity parameters (rs = 0.241-0.277) and were
      also correlated with the visual analog scale score for skin lesion severity.
      Morning stiffness of peripheral joints was correlated only with two AIMS scales,
      namely pain (rs = 0.532) and activities of daily living (rs = 0.303). Severity of
      radiological damage of peripheral and axial joints was most closely correlated
      with the scales of physical function, most notably physical activity. The global
      and scale HAQ scores showed moderate to close correlations with the main clinical
      disease activity parameters, most notably morning stiffness of axial joints. The
      global HAQ score was also correlated with radiological carpal involvement and
      with the radiological severity of peripheral joint involvement, whereas only the
      arising and hygiene scales were (moderately) correlated with the radiological
      severity of spinal involvement. CONCLUSION: Although both the HAQ and the AIMS
      were useful in assessing health status in psoriatic arthritis patients, only the
      AIMS captured some of the effects of the skin lesions. Our data also suggest that
      the AIMS may be more effective than the HAQ for evaluating the effect of
      radiological lesions produced by psoriatic arthritis.

PMID- 9923044
TI  - Increased serum C-reactive protein levels by immunonephelometry in patients with
      rapidly destructive hip osteoarthritis.
AB  - OBJECTIVE: To compare serum C-reactive protein levels measured using a highly
      sensitive immunonephelometry method in patients with rapidly destructive versus
      slowly progressive hip osteoarthritis. METHODS: Ten patients meeting criteria for
      rapidly destructive hip osteoarthritis were compared to 25 patients with slowly
      progressive hip osteoarthritis defined as less than 0.20 mm joint space loss over
      the last year. Serum C-reactive protein was assayed using an immunonephelometry
      method with a detection threshold of 0.17 mg/L and a coefficient of variation of
      less than 5%. RESULTS: One patient in each group was excluded because of a C
      reactive protein level greater than 15 mg/L. The mean C-reactive protein level in
      the remaining 33 patients was 3.05 +/- 3.46 mg/L (range, 0.10-14.9 mg/L). Mean C
      reactive protein was significantly higher in the rapidly destructive group than
      in the slowly progressive group (5.61 +/- 4.75 versus 1.94 +/- 1.98 mg/L, P =
      0.01), even after adjustment for potential confounding factors. CONCLUSION: Our
      data suggest that rapidly destructive hip osteoarthritis may be associated with
      some degree of inflammation reflected by a small but significant increase in
      serum C-reactive protein levels.

PMID- 9923045
TI  - Epidemiology and features of knee osteoarthritis in the Ivory Coast.
AB  - We retrospectively studied 369 cases of knee osteoarthritis in 240 patients seen
      at the Cocody Teaching Hospital in Abidjan, Ivory Coast, from November 1984
      through March 1989. There were 126 cases (34.14%) of patellofemoral
      osteoarthritis, 104 cases (28.18%) of femorotibial osteoarthritis and 139 cases
      (37.66%) of global knee osteoarthritis (defined as patellofemoral and
      femorotibial osteoarthritis in the same joint). There was a marked female bias
      (80.42% of patients). Onset was earlier in patellofemoral osteoarthritis (51.25
      years) than in femorotibial osteoarthritis (57.85 years). Half the patients
      (51.25%) were housewives. The Akan and Mande ethnic groups contributed 61.54% and
      33.03% of patients, respectively. Obesity was present in 19.04% of cases of
      patellofemoral osteoarthritis and in 10.57% of cases of femorotibial
      osteoarthritis. Of the patients with femorotibial osteoarthritis, 20.20% had a
      history of arthritis of the knee and of those with global knee osteoarthritis,
      12.23% reported a prior injury to the knee. Varus deformity was found in 24.03%
      and valgus deformity in 19.23% of the patients with femorotibial osteoarthritis.

PMID- 9923047
TI  - Osteopetrosis as a model for studying bone resorption.

PMID- 9923046
TI  - Adhesive capsulitis of the shoulder: therapeutic contribution of subacromial
      bursography.
AB  - OBJECTIVE: To demonstrate the therapeutic value of subacromial bursography (with
      a steroid injection) in adhesive capsulitis of the shoulder inadequately improved
      by arthrographic glenohumeral distension with steroid injection. METHOD: Twenty
      cases of adhesive capsulitis documented by glenohumeral arthrography were studied
      prospectively. A steroid was injected during distension arthrography, which was
      followed by physical therapy. Subacromial bursography without steroid injection
      was done routinely for diagnostic purposes. Constant's simplified score and range
      of motion were determined in each patient at baseline and after one, three, six
      and 12 months. Patients who were inadequately improved after one to three months
      underwent repeat subacromial bursography with steroid injection, followed by
      physical therapy. RESULTS: Of the 20 patients, 13 were noticeably improved 1.7
      months on average after the distension arthrography. Of the remaining seven
      patients, six were improved 0.7 months on average after the bursography with
      steroid injection. CONCLUSION: Glenohumeral distension arthrography with steroid
      injection followed by physical therapy is effective in expediting the
      spontaneously favorable outcome of adhesive capsulitis and also allows to confirm
      the diagnosis. However, the subacromial bursa is almost consistently involved.
      Subacromial bursography with steroid injection can be useful in cases that fail
      to respond to conventional therapy.

PMID- 9923048
TI  - HHV8 status in Kaposi's sarcoma associated with multiple myeloma.
AB  - Kaposi's sarcoma in its sporadic or HIV-related form is due to a gamma
      herpesvirus, the human herpes virus 8 (HHV8). No data have been published on the
      potential role of the HHV8 in Kaposi's sarcoma occurring in multiple myeloma
      patients. A case is reported of a patient in whom four serum samples taken
      between the diagnosis of multiple myeloma and the occurrence of a Kaposi's
      sarcoma one year later tested positive for antibody to the HHV8. Similar findings
      have been reported in patients with other types of Kaposi's sarcoma. PCR studies
      for HHV8 DNA were positive on a Kaposi's sarcoma biopsy but negative on a bone
      biopsy, militating against a role for the HHV8 in the genesis of multiple
      myeloma.

PMID- 9923049
TI  - Tuberculosis of the sternoclavicular joint. Report of two cases.
AB  - The sternoclavicular joint accounts for only 1 to 2% of all cases of peripheral
      tuberculous arthritis and is more often infected by pyogenic organisms than by
      the tubercle bacillus. We report two cases of sternoclavicular joint
      tuberculosis, in a 38-year-old man and a 46-year-old woman without risk factors
      for immune deficiency. Swelling of the joint was the presenting manifestation.
      Laboratory tests indicated inflammation in only one of the patients. The
      intradermal tuberculin test was strongly positive in both patients, whereas
      smears and cultures of sputum and urine samples were negative for the tubercle
      bacillus. Serologic tests for the human immunodeficiency virus were negative.
      Erosions of the affected joint were seen by computed tomography. Histological
      studies of a surgical biopsy specimen confirmed the diagnosis. Cultures of the
      biopsy specimens were negative. The outcome was favorable after treatment with
      rifampin, isoniazid and pyrazinamide for six months in the man and nine in the
      woman. Follow-ups were eight and six months, respectively, at the time of this
      writing. Tuberculosis of the sternoclavicular joint is extraordinarily rare and
      can raise diagnostic problems. The diagnosis should be considered in every
      patient with arthritis in a sternoclavicular joint or unexplained pain in a
      shoulder. Possible complications include compression or erosion of the large
      blood vessels at the base of the neck and migration of tuberculous abscesses to
      the mediastinum.

PMID- 9923051
TI  - Femoral neck stress fracture in a woman with dromomania due to delusions of
      possession.

PMID- 9923050
TI  - Reactive oligoarthritis in a patient with Clostridium difficile pseudomembranous
      colitis. Review of the literature.
AB  - A 57-year-old man developed oligoarthritis of the right sacroiliac joint, knee
      and elbow in the wake of Clostridium difficile pseudomembranous colitis. He was
      HLA B27-positive and had a history of Reiter's syndrome. His joint manifestations
      resolved after a course of nonsteroidal antiinflammatory drug therapy and
      injection of the right knee with triamcinolone acetonide. Clostridium difficile
      should be recognized as a rare cause of reactive arthritis.

PMID- 9923052
TI  - Use of methotrexate in the management of rheumatoid arthritis in Dakar. Potential
      pitfalls.

PMID- 9923053
TI  - Adhesive capsulitis of the shoulder induced by protease inhibitor therapy. Three
      new cases.

PMID- 9923054
TI  - Concomitant ankylosing spondylitis and Sjogren's syndrome in three patients.

PMID- 9923055
TI  - Mucin gene expression and mucin secretion in human airway epithelium.

PMID- 9923056
TI  - Experimentally induced nasal hypersecretion does not reduce the efficacy of
      intranasal levocabastine.
AB  - In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for
      usage on an as-needed basis, because it has a quick onset of action, and many
      patients prefer to take medicine only when they have symptoms. It is a
      prerequisite, however, that nasal hypersecretion during a rhinitis episode does
      not significantly reduce the efficacy of intranasal treatment by washing away the
      drug before it reaches the H1-histamine receptors. In order to investigate this
      problem, we have induced nasal hypersecretion with a methacholine challenge in
      one experiment and in four experiments we have washed the nasal cavities 0.5 min.
      before, 5 min. before, 0.5 min. after and 5 min. after intranasal use of the H1
      antagonist, levocabastine. The symptom response to a subsequent histamine
      challenge was used as the effect parameter. Levocabastine reduced the number of
      histamine-induced sneezes with 81% (p < 0.0001) and the secretion weight with 62%
      (p < 0.001) compared with placebo. Neither methacholine-induced hypersecretion
      nor washing the nose with saline reduced the efficacy of the antihistamine spray.
      We conclude that experimentally induced nasal hypersecretion does not reduce the
      efficacy of the antihistamine spray, and probably the same applies to rhinorrhea
      during an acute episode of allergic rhinitis.

PMID- 9923057
TI  - Mechanisms of IL-6, IL-8, and GM-CSF release in nasal secretions of allergic
      patients after nasal challenge.
AB  - Cytokines are potentially active biological peptides that are known to play an
      important role in several immune responses. Several studies have reported the
      existence of a variety of cytokines in the nasal mucosa of patients with allergic
      rhinitis. However, there are few reports on cytokines released into the nasal
      secretion. In the present study, we investigated the sources, and levels of three
      key proinflammatory cytokines namely, IL-6, IL-8, and GM-CSF in the nasal
      secretion, as well the mechanisms of their release, by ELISA and
      immunohistochemistry. Firstly, we examined the levels of IL-6, IL-8, and GM-CSF
      in the nasal secretion after in vivo nasal challenge with methacholine (MC),
      histamine (HI) and allergen (Ag) in patients with nasal allergy to house dust
      mite (HDMAR). Next, we examined the levels of IL-6, IL-8, and GM-CSF released, in
      vitro, after Ag challenge of nasal scrapings from patients with HDMAR. Finally,
      we examined the sources of these cytokines in the nasal mucosa, by
      immunohistochemistry. After MC challenge in patients with HDMAR, the
      concentration of IL-6, but not IL-8, and GM-CSF, was significantly greater on the
      challenged side than on the contralateral side. Ag and HI provocation induced
      significantly greater levels of IL-6 and IL-8 secretion in patients with HDMAR,
      on the challenged side than on the contralateral side. GM-CSF was only detected
      in the nasal secretion after Ag challenge. Immunoreactivity for IL-6 and IL-8 was
      very similar in that it was predominantly localised to the apical portion of
      epithelial cells, the superficial lamina propria, gland cells, and migrating
      cells. The immunoreactivity for GM-CSF varied slightly from that of IL-6 and IL
      8: strong immunoreactivity was detected in the basal part of epithelial cells,
      basement membrane, glandular ducts, and migrating cells. These results suggest
      that the levels, sources, and mechanisms of release of IL-6, IL-8, and GM-CSF in
      the nasal secretion of patients with HDMAR do vary, but are important in the
      manifestation of the allergic reaction.

PMID- 9923058
TI  - Evaluation of some important anatomical variations and dangerous areas of the
      paranasal sinuses by CT for safer endonasal surgery.
AB  - The purpose of this study is to determine some important variations and dangerous
      areas carrying risks for major complications, in the routine CT examination. We
      also made specific measurements to evaluate the individual differences. This
      prospective study consisted of 111 patients (222 sides). Eighty patients
      underwent coronal, and the rest coronal and axial CT. The depth of lamina
      cribrosa, its distance to the inferior turbinate, and the distance of anterior
      ethmoidal artery (AEA) either to the orbital roof or inferior turbinate were
      measured. Variations of the upper attachment of uncinate process were encountered
      in 23%. AEA coursed freely within ethmoidal cells in 43%. Anterior clinoid
      aeration was seen in 14%, optic canal bulging into the sphenoid sinus in 13% and
      an extreme medial course of the carotid canal in 12% of the patients. The mean
      depth of lamina cribrosa was 5.9 mm, and its mean distance to the inferior
      turbinate was 25.7 mm. The mean distance of AEA to the orbital roof was 13.7 mm,
      and to the inferior turbinate 30.05 mm. Anterior clinoid aeration correlated well
      with the variations of carotid and optic canals, statistically (p < 0.01). A
      detailed CT study will provide important information on the areas carrying risks
      of complications and the size of the area to be worked on.

PMID- 9923059
TI  - Responses to nasal irritation obtained from the human nasal mucosa.
AB  - Responses to chemical irritation can be obtained from the human respiratory
      mucosa in response to stimulation with gaseous CO2; these negative mucosal
      potentials (NMPs) are thought to be summated receptor potentials from
      chemosensitive nociceptors. The present study aimed to investigate the relation
      of this response to both stimulus concentration and perceived intensity. A total
      of 29 healthy volunteers participated. Maximum negative amplitudes occurred 1.1 s
      after stimulus onset. The negativity exhibited a higher coefficient of
      correlation to intensity estimates of the painful sensations (r = .65) than to
      the stimulus concentration (r = .46); it appeared at the same time when the
      subjects' tracking of the painful sensations reached its maximum amplitude. These
      findings suggest that the NMP is suited for the investigation of peripheral
      nociceptive events in man.

PMID- 9923060
TI  - Cefuroxime axetil versus clarithromycin in the treatment of acute maxillary
      sinusitis.
AB  - Acute maxillary sinusitis is a common condition requiring broad-spectrum therapy
      to prevent development of chronic disease. A randomised, double-blind,
      multicentre study was performed to compare the efficacy and safety of cefuroxime
      axetil 250 mg twice daily (n = 185) and clarithromycin 250 mg twice daily (n =
      185), both administered for 10 days, in the treatment of patients with acute
      sinusitis. Efficacy was determined by assessment of clinical response at post
      treatment and follow-up, and by radiological assessment at pre-treatment and
      follow-up. Assessment of days absent from work due to illness was also made. In
      the cefuroxime axetil group, 169/185 (91%) patients were cured/improved at post
      treatment, as were 172/185 (93%) patients receiving clarithromycin and, of these,
      137/169 (81%) and 143/172 (83%) maintained their response at follow-up. Follow-up
      radiography showed a reduction in incidence of air fluid level and/or
      opacification from 96% to 15% (cefuroxime axetil) and from 96% to 11%
      (clarithromycin), and a decrease in frequency of mucosal thickening from 58% to
      28% (cefuroxime axetil) and from 56% to 29% (clarithromycin). Only 10% of
      patients in either group experienced adverse events and days absent from work
      were comparable. This study demonstrated clinical equivalence between twice-daily
      cefuroxime axetil and clarithromycin, both treatments being effective and well
      tolerated.

PMID- 9923061
TI  - Improved nasal breathing in snorers increases nocturnal growth hormone secretion
      and serum concentrations of insulin-like growth factor 1 subsequently.
AB  - In snoring men improved nasal breathing during sleep has been shown to decrease
      snoring and morning tiredness. The aim was to evaluate whether improved nasal
      breathing had any effect on growth hormone (GH) secretion, the nocturnal
      secretion of GH being associated with deep sleep. Forty-two snoring men, mean age
      45 years and mean body mass index 26 kg.m-2, slept every night during one month
      with the Nozovent nostril dilator. Before and at the end of the test period, we
      analysed serum insulin-like growth factor 1 (IGF-1), thyrotropin (TSH), free
      thyroxine (free T4), free 3,5,3'-triiodothyronine (free T3), cortisol and
      testosterone in blood sampled at 08:00 h. Fifteen of the 37 snoring men who
      completed the study experienced a reduction in snoring and were less tired in the
      morning during the test period. In this group, the mean IGF-1 concentration was
      significantly increased (p < 0.05) after one month. There was no significant
      difference in mean IGF-1 level between the snorers and a population sample.
      Likewise, TSH, free T4, free T3, cortisol and testosterone concentrations were
      within normal limits. Snorers with reduced snoring and morning tiredness due to
      improved nasal breathing showed an increase in morning IGF-1 concentration which
      can probably be explained by higher nocturnal GH secretion induced by more deep
      sleep.

PMID- 9923062
TI  - The role of acoustic rhinometry in the pre- and postoperative evaluation of
      surgery for nasal obstruction.
AB  - This is a prospective study evaluating the role of acoustic rhinometry (AR) in
      the measurement of nasal patency before and after surgery for nasal obstruction.
      We examined 27 patients before and 2 to 6 months after septoplasty associated
      with turbinoplasty, cauterisation of the inferior turbinates, rhinoplasty or
      uvulopalatopharyngoplasty in some cases. Surgery was performed for subjective
      nasal obstruction and indication based on symptoms and clinical findings. AR was
      performed after indication was made. Patients were evaluated for this study by
      marking subjective global nasal obstruction on a visual analogue scale and by AR
      before and after decongestion. All patients noted an improvement of subjective
      nasal patency after surgery. Mean unilateral minimal cross-sectional area (MCA)
      of the preoperatively narrower side and total MCA both increased but showed wide
      ranges with also negative results. The total volume of the nasal fossae did not
      increase. The volume of the preoperatively narrower nasal fossa increased with
      surgery, but there are enormous ranges. We could not find any correlation between
      the MCA of the preoperatively narrower side or the total MCA and subjective nasal
      patency, neither before nor after surgery. The same was the case for the volume
      of the nasal fossae. In our opinion AR is not a valuable method for the
      indication or evaluation of surgery for nasal obstruction.

PMID- 9923063
TI  - Wegener's granulomatosis--a review of diagnosis and treatment in 53 subjects.
AB  - We reviewed 79 patients with clinically suspected Wegener's granulomatosis (WG)
      diagnosed in Nottingham between 1990 and 1997. Fifty-three patients were
      confirmed as having WG. We describe the symptoms and signs, features of
      diagnostic significance, ANCA results, biopsy sites, histology, treatment and
      outcome in this group. Nasal symptoms and signs had a positive predictive value
      of 63%, c-ANCA at presentation 100%, and positive nasal biopsy 100%. The negative
      predictive values were 41%; 79% and 74% respectively. From this study, we
      recommend that patients who have a negative ANCA and where there remains a
      clinical suspicion of WG, an ENT examination should be undertaken. Whilst a
      suspicious lesion should be biopsied and a positive histological picture has a
      100% positive predictive value, a negative nasal biopsy does not exclude WG as 5
      patients went on to develop a positive ANCA up to 4 years later. In 11 ANCA
      negative patients where there were signs of nasal mucosal disease, 6 had a
      positive biopsy and this highlights the importance of nasal biopsy. The c-ANCA
      should be repeated in patients with a negative c-ANCA and biopsy results at
      presentation, in whom there remains a clinical suspicion of WG.

PMID- 9923064
TI  - Maxillary sinus mucocoeles--10 cases--8 treated endoscopically.
AB  - Maxillary sinus mucocoeles are rare, but may cause significant problems outside
      the sinus including diplopia and cheek swelling. We present 9 patients suffering
      from maxillary sinus mucocoele, including one patient with bilateral involvement,
      representing 10 involved sinuses. Eight sinuses were treated endoscopically and
      followed-up for 3 to more than 6 years; one of these developed a recurrence. Two
      sinuses were treated using a classical external approach (Caldwell-Luc), one at
      the beginning of our series, and one as the endoscopic technique was difficult to
      perform due to loss of anatomical landmarks. One of these two sinuses developed a
      recurrence and was then successfully treated endoscopically. We discuss the
      aetiology, pathogenesis and appropriate treatment of this unusual condition.
      Endoscopic treatment appears to be effective and leads to minimal recurrence. The
      aim is to perform a wide removal of the medial wall of the maxillary sinus
      including most of the inferior turbinate, immediately posterior to the lachrymal
      duct leaving intact the sinus mucosa. In some cases, however, the endoscopic
      technique can be difficult to perform due to loss of essential anatomical
      landmarks and in these cases recourse to an external approach may be necessary.

PMID- 9923065
TI  - Combined functional endoscopic sinus surgery (FESS): a revisited approach.
AB  - A technique of combined functional endoscopic sinus surgery (FESS) was carried
      out through the nose to clear up the ostiomeatal complex. A small window was then
      created in the canine fossa to remove the maxillary sinus pathology under
      endoscopic control. It aims at the complete removal of maxillary sinus pathology,
      which cannot be safely removed via the middle meatus while preserving the rest of
      the mucosa to ensure sinus rehabilitation. It also helps the surgeon in case of
      difficulty in locating the ostium during FESS. A series of 36 patients was
      studied over a period of two years, with a follow up, up to two years, post
      operatively. The present technique proved to be complementary to FESS with no
      serious complications. It is recommended for cases of recurrent antrochoanal
      polyps, oroantral fistula, sinusitis of dental origin or fungal infection of the
      nose and sinuses.

PMID- 9923066
TI  - Septal mucoperichondrial flap for closure of nostril in atrophic rhinitis.
AB  - The aetiology of primary atrophic rhinitis is still unknown. Treatment of this
      disease is conservative in the first place. Surgery is indicated if the medical
      treatment fails. The aim of surgery is either to narrow the nasal cavity or in
      special cases to close the nostril. Closure of the nostril (Young's operation),
      is achieved by raising a circular skin flap. Raising the skin flap is difficult,
      the suture line may break down and an excessive scar tissue may form resulting in
      vestibular stenosis. We therefore developed a septal mucoperichondrial flap to
      close the nostril. This new and easy technique has been used to treat 17 patients
      with excellent results. The description of this technique and the results of
      surgery will be discussed.

PMID- 9923067
TI  - Septorhinoplasty under general anaesthesia.

PMID- 9923068
TI  - Adolescent depression. Epidemiology, nosology, life stress and social network.
      Minireview based on a doctoral thesis.
AB  - The study engaged a total population of 16-17-year-old urban high-school students
      and 2300 (93%) were screened for depression and previous suicide attempts.
      Adolescents with high depression scores in self-evaluation (12.3%) or reporting
      previous suicide attempts (2.4%) were diagnostically interviewed together with
      one control for each, matched for gender and educational program. After the
      interview self-ratings were completed regarding social network, family climate,
      and life events. Major depression was prevalent during the last year in 5.8% and
      during life time in 11.4%, 4 girls for every boy. A depression with remaining
      symptoms for a year or more was the most common type. Dysthymia without major
      depressive episodes was diagnosed in 1.1%, two girls for every boy. Short
      hypomanic episodes had been experienced by 13.2% of those with major depressive
      disorder. Anxiety disorder was comorbid to depression in one half and conduct
      disorder in one forth of the depressed adolescents. Alcohol was abused by 6.5%
      and used regularly by another 12%. Other drugs were used by 6.5% of depressed
      adolescents and not at all by controls. The depressed used tobacco twice as
      frequently as non-depressed. Social network and family climate were compared
      within the originally matched pairs. Adolescents with long-lasting depressions
      had a smaller and unsatisfying social network. They also had experienced many
      stressful life events related to family adversities, while those with shorter
      depressive episodes had stress related to the peer group. Depressed adolescents
      with comorbid conduct disorder reported insufficient support from the close
      network and a more negative family climate.

PMID- 9923069
TI  - Efficiency of cytological screening for detection of cervical squamous carcinoma.
      A study in the county of Uppsala 1991-1994.
AB  - Squamous carcinoma of the uterine cervix accounts for a considerable mortality
      among gynecological malignancies, although both the incidence of and mortality
      from cervical cancer have decreased in the Nordic countries since 1970. The
      reduction is a result of the cytologic screening program, through which precursor
      lesions can be detected and removed. Our aim was to determine why women in the
      county of Uppsala get cervical cancer despite extensive gynecological screening.
      A retrospective study of all women (43 cases) who developed histologically
      verified cervical squamous carcinoma in the county of Uppsala during the years
      1991 to 1994 was undertaken. A central computer database covering all
      histopathological and cytological material made it possible to compare each
      woman's previous smears or lack of smears with her cancer diagnosis. Twenty women
      (47%, mean age at diagnosis 64.4 years) had not undergone cytological screening.
      Twenty-three women (53%) had been screened at least once within 6 years before
      tumor diagnosis. Of these, 11 (mean age 47.5 years) had had normal smears for the
      last 6 years, 8 (mean age 44.3 years) had shown abnormal cytology for less than
      one year and 4 (mean age 39.0 years) had shown abnormal cytology for more than
      one year and up to 6 years before their cervical cancer diagnosis. Women with
      cervical squamous carcinoma, who are not covered by the gynecological screening
      program (47%) are at increased risk of developing cervical cancer compared with
      other women. Consequently the average age of non-screened women developing cancer
      is considerably higher (64.4 years) than that of women with cancer screened
      previously (44.9 years). In 26% of the total group of women with cervical
      squamous carcinoma previous cytology displayed normal features.

PMID- 9923070
TI  - Recurring themes in oocyte maturation.
AB  - I am pleased to contribute to this special issue of Biology of the Cell in honor
      of Yoshio Masui. Oocyte maturation remains a small enough and young enough field
      that the authors assembled for this issue can trace the entire development of the
      field over the last 30 years, beginning with the early demonstration by Masui
      (1967) and others, that steroids can induce complete maturation of denuded
      oocytes in vitro. Not very long after that Masui and Markert (1971) published the
      seminal paper that identified MPF and CSF activity. In this article I intend to
      highlight recurring themes in oocyte maturation that continue to be actively
      investigated, almost all of which derive from studies pursued at some point in
      time by Masui and his colleagues.

PMID- 9923071
TI  - Cytoplasmic control of nuclear behavior during meiotic maturation of frog
      oocytes.
AB  - The title of this article is taken from a 1971 publication by Yoshio Masui and
      Clement Markert in which they describe the discoveries of the meiotic regulatory
      activities maturation promoting factor and cytostatic factor. Here we review the
      experiments that led to these discoveries and discuss their relation to our
      current knowledge of the biochemistry of oocyte maturation.

PMID- 9923072
TI  - Maturation promoting factor activation in early amphibian embryos: temporal and
      spatial control.
AB  - The cytoplasmic localisation of factors capable of influencing the behaviour of
      nuclei has long been considered a potential mechanisms for generating cell
      differences during development. Yoshio Masui was instrumental in identifying two
      cytoplasmic factors, maturation promoting factor (MPF) and cytostatic factor
      (CSF), defining the first biological assay for their isolation and
      characterisation. These biological assays involved the transfer of cytoplasm
      between amphibian oocytes, MPF being able to promote meiotic maturation
      (progression to MII) and CSF to stabilise the MII state. Masui was subsequently
      involved in developing a 'cell-free' system with the potential for analysis not
      just of MPF and CSF, but many aspects of nucleo-cytoplasmic interaction. Masui
      and Markert initially showed that MPF activity could be generated in enucleate
      oocytes following progesterone stimulation, indicating a cytoplasmic origin.
      Masui subsequently showed that MPF activity was distributed unevenly through the
      egg of Rana pipiens during maturation. In this review we will consider the
      historical context in which the MPF assays were established, then briefly
      consider some of the molecular components that are now known to influence MPF
      activation. We will then consider evidence for the asymmetric activation of MPF
      and the possibility that the nucleus contributes to MPF activation in early
      embryos.

PMID- 9923073
TI  - Raf-1 kinase, a potential regulator of intracellular pH in Xenopus oocytes.
AB  - Xenopus laevis oocytes undergo an increase in intracellular pH (pHi) from 7.2 to
      7.7 due to the up-regulation of Na+/H+ antiporters in their plasma membrane
      during oocyte meiotic maturation. Up-regulation of Na+/H+ exchangers (NHE) found
      in other cell systems appears to be controlled, in some cases, by direct
      phosphorylation of the exchanger. A number of active protein kinases can be found
      in maturing Xenopus oocytes. These include, c-mos kinase, Raf-1 kinase, mitogen
      activated kinase kinase (MAPKK), MAPK, ribosomal S6 kinase (RSK), and histone H-1
      kinase. Our previous study indicated that c-mos kinase, was involved in
      regulating the increase in oocyte pHi. In the current study, we show that when
      mRNA coding for a constitutively active form of Raf-1 kinase (delta N-Raf-1) was
      microinjected into oocytes, the protein product induced an increase in oocyte
      pHi. On the contrary, the injection of mRNA coding for wild-type Raf-1 (WT-Raf-1)
      or a kinase-deficient form of Raf-1 (KD-Raf-1) had no effect on the recipient
      oocyte pHi. 8-Br-cAMP and forskolin blocked the increase in pHi during oocyte
      meiotic maturation, but had no effect on the Raf-1-induced increase in oocyte
      pHi. Studies using antisense c-mos oligos demonstrated that Raf-1 was not working
      via a feedback loop to endogenous c-mos mRNA within the recipient oocytes.
      Experiments using the selective MAPKK inhibitor, PD 98059, indicated that the Raf
      1 effect on oocyte pHi was not mediated by the downstream kinase, MAPKK.
      Therefore, Raf-1 appears to act independently of c-mos kinase in a pathway, not
      involving MAPKK, leading to the up-regulation of the Na+/H+ antiporters in
      Xenopus oocytes.

PMID- 9923074
TI  - Germinal vesicle material is dispensable for oscillations in cdc2 and MAP kinase
      activities, cyclin B degradation and synthesis during meiosis in Xenopus oocytes.
AB  - We have investigated at a molecular level the requirements for germinal vesicle
      (nuclear) material during the course of meiosis in Xenopus oocytes. We present
      the localization of some cell cycle proteins in stage VI oocytes; most of those
      analyzed are cytoplasmic, although some (MAD, 26S proteasome) are distributed
      between the cytoplasm and the germinal vesicle. By analyzing changes in
      individual oocytes, we find that the unphosphorylated form of cyclin B2
      disappears and the phosphorylated form is then degraded in both nucleated and
      enucleated oocytes. Enucleated oocytes are also capable of resynthesizing both
      cyclin B1 and cyclin B2 after the initial degradation and of reactivating cdc2
      kinase. Synthesis of mos protein and activation of MAP kinase concomitant with
      cdc2-cyclin B reactivation are also unaffected by prior removal of the germinal
      vesicle.

PMID- 9923075
TI  - Overexpression of the cytoplasmic retention signal region of cyclin B2, but not
      of cyclin B1, inhibits bipolar spindle formation in Xenopus oocytes.
AB  - Cyclin B, a regulatory subunit of maturation/M-phase promoting factor (MPF), has
      several subtypes in many vertebrate species. However, it is not known whether the
      different B-type cyclins have any different functions in vertebrate cells,
      although their subcellular localizations seem to differ largely from each other.
      To examine the roles of two major B-type cyclins, B1 and B2, in spindle formation
      in M phase, we overexpressed their N-termini in Xenopus oocytes; the N-termini of
      cyclins B1 and B2 contained a cytoplasmic retention signal (CRS), and hence their
      overexpressions were expected to competitively inhibit the subcellular
      localizations of the endogenous cyclins B1 and B2, respectively. Upon entry into
      meiosis I, oocytes overexpressing the cyclin B1 N-terminus formed an apparently
      normal bipolar spindle, but those oocytes overexpressing the cyclin B2 N-terminus
      formed a monopolar (or monoastral) spindle. This defect in bipolar spindle
      formation was observed only when the cyclin B2 N-terminus contained its own CRS
      sequence, and was able to be rescued by overexpression of full-length cyclin B2.
      These results suggest, for the first time, that the correct subcellular
      localization of cyclin B2, but not of cyclin B1, is essential for (the initiation
      of) bipolar spindle formation in Xenopus oocytes.

PMID- 9923076
TI  - An indirect role for cyclin B-Cdc2 in inducing chromosome condensation in Xenopus
      egg extracts.
AB  - We have studied the cytoplasmic mechanism that induces metaphase chromosome
      condensation in cell-free Xenopus egg extracts. To analyze the mechanism
      responsible for inducing chromosome condensation separately from those
      responsible for sperm chromatin remodeling and nuclear envelope disassembly, we
      used Xenopus sperm chromatin that had already been remodeled to nucleosomal
      chromatin by incubating demembranated sperm with egg extracts added with
      lysolecithin. We found that inhibition of cyclin B-Cdc2 with butyrolactone I
      abolished chromosome condensation of the remodeled sperm chromatin by M-phase egg
      extracts, but incubation of the chromatin with active cyclin B-Cdc2 alone did not
      induce chromosome condensation, indicating a requirement for cytoplasmic
      factor(s) in addition to cyclin B-Cdc2 for the induction of chromosome
      condensation. We further demonstrated that if the cyclin B-Cdc2-dependent
      phosphorylation state was protected against dephosphorylation by a preincubation
      of M-phase extracts with ATP-gamma-S, chromosome condensation and phosphorylation
      of chromosomal histone H1 occurred even when extracts were depleted of cyclin B
      Cdc2 activity. The chromosome condensation seen in the absence of cyclin B-Cdc2
      was completely inhibited with another protein kinase inhibitor, 6
      dimethylaminopurine, implying that a protein kinase other than cyclin B-Cdc2 was
      involved in the induction of chromosome condensation. These results strongly
      suggest that a cyclin B-Cdc2-dependent protein kinase cascade is involved in
      inducing chromosome condensation and the phosphorylation of chromosomal histone
      H1.

PMID- 9923077
TI  - Retention in reversed-phase chromatography: partition or adsorption?
AB  - A unified framework within the hermeneutics of the solvophobic theory is employed
      for the treatment of experimental data with nonpolar and weakly polar substances
      in reversed-phase chromatography (RPC), oil-water partitioning and adsorption on
      activated charcoal from dilute aqueous solution. This approach sheds light on the
      energetic similarities between such processes driven by the hydrophobic effect.
      Among several stationary phase models that have been proposed in the literature
      for the physical representation of alkyl-silica bonded phases, the isolated
      solvated hydrocarbon chains model is adopted for the retention in RPC since it
      represents most closely the stationary phase configuration and is not based a
      priori on a partition or adsorption mechanism as some other models are for the
      retention in RPC. Using the fundamental framework of the solvophobic theory, the
      free energy change per unit nonpolar surface area for octanol-water and
      hexadecane-water partitioning, retention in RPC as well as adsorption on
      activated charcoal from dilute aqueous solution at 25 degrees C are evaluated and
      they are found to be in good agreement with the corresponding experimental data.
      Furthermore, such quantities are very similar for all the above mentioned
      processes involving aqueous solution, in contradistinction to the predictions by
      the lattice theory. From the results it follows that these apparently disparate
      processes are subject to the same physicochemical principle. The present study
      demonstrates the capability of the solvophobic theory in describing the
      energetics of processes involving hydrophobic interactions, and exposes the
      difficulties in distinguishing between partition and adsorption mechanisms in RPC
      by using partition models based on the lattice approach. It is concluded that a
      clear distinction between partition and adsorption in RPC of nonpolar elites is
      not apparent from thermodynamic analysis.

PMID- 9923078
TI  - High-performance liquid chromatography with electrospray ionization mass
      spectrometry and diode array ultraviolet detection in the identification of
      flavonol aglycones and glycosides in berries.
AB  - High-performance liquid chromatography-electrospray ionization-mass spectrometry
      (HPLC-ESI-MS) was used to study flavonol aglycones and glycosides in berries. For
      the identification of aglycones, photodiode-array detection (DAD) was also used.
      The HPLC-ESI-MS technique is highly valuable in the identification of flavonol
      aglycones and glycosides from berry extracts. This ionization technique provides
      information on the structure of the aglycones and glycosides without time
      consuming pre-purification or derivatization steps. Quercetin aglycone was
      identified with both ESI-MS and DAD in all of the berries studied. Myricetin
      aglycone was identified with both techniques in three berries. Hexose,
      deoxyhexose-hexose and pentose derivatives of quercetin were the most abundant
      flavonol glycosides identified. Two glycosides of myricetin and one glycoside of
      kaempferol were identified in blackcurrant. To confirm the data obtained using
      the HPLC-ESI-MS procedure, fractions of the glycosides from four berries were
      separated, hydrolyzed, silylated and the sugars were analyzed using gas
      chromatography-mass spectrometry.

PMID- 9923079
TI  - Characterization of metallothionein isoforms by reversed-phase high-performance
      liquid chromatography with on-line post-column acidification and electrospray
      mass spectrometric detection.
AB  - Post-column acidification of the chromatographic effluent was developed to
      eliminate artefacts in investigations of the polymorphism of metallothionein (MT)
      by microbore reversed-phase HPLC with detection by pneumatically assisted
      electrospray mass spectrometry. Metallated species (Cd, Zn and mixed Cd-Zn
      complexes) were decomposed on-line to produce apo metallothioneins of which the
      molecular masses were determined by MS. Besides the simplification of the mass
      spectra taken at the apexes of the chromatographic peaks, the method resulted in
      a 10-fold improvement of the detection limit of metallothionein and allowed a
      more comprehensive and less ambiguous detection and identification of the iso-
      and subisoforms. The method was applied to the characterization of rabbit liver
      metallothioneins: rabbit liver MT (purified by size-exclusion chromatography
      only) and MT-1 and MT-2 isoform fractions purified additionally by anion-exchange
      chromatography.

PMID- 9923080
TI  - Application of analytical and preparative high-speed counter-current
      chromatography for separation of alkaloids from Coptis chinensis Franch.
AB  - Analytical high-speed counter-current chromatography (HSCCC) was used for the
      systematic selection and optimization of the two-phase solvent system to separate
      alkaloids from Coptis chinensis Franch. The optimum solvent system thus obtained
      led to the successful separation of alkaloids from C. chinensis Franch by
      preparative HSCCC. One batch separation yielded four pure alkaloids, including
      palmatine, berberine, epiberberine and coptisine from the crude alkaloid extract.

PMID- 9923081
TI  - Determination of trace level bromate in drinking water by direct injection ion
      chromatography.
AB  - Disinfection byproduct anions such as bromate, chlorite and chlorate pose
      significant health risks, even at low microgram/l levels in drinking water. A
      direct injection, ion chromatographic method was developed using a Dionex AS9-HC
      anion-exchange column with a carbonate eluent and suppressed conductivity
      detection for the determination of these disinfection byproduct anions, and
      bromide, at low microgram/l levels in drinking water. No additional sample
      pretreatment, other than filtration, is required. The method is linear for the
      oxyhalides and bromide over the typical concentration range expected for these
      analytes in drinking water; and quantitative recoveries were obtained for
      drinking water samples spiked at 10 micrograms/l. This ion chromatographic
      method, based on the recently developed AS9-HC column, is applicable for the
      quantitation of bromate in finished drinking water at the 10 micrograms/l maximum
      contaminant level currently being proposed by the US EPA.

PMID- 9923082
TI  - Solid-phase microextraction with pH adjustment for the determination of aromatic
      acids and bases in water.
AB  - Adjusting the pH of water samples before performing solid-phase microextraction
      (SPME) analysis can be used to selectively extract organic acids (at pH 2) and
      bases (at pH 12). Sorption behavior of test organics is predictable based on the
      acid dissociation constant in water. In general, polyacrylate (PA) and Carbowax
      divinylbenzene (CW-DVB) show substantially higher fiber/water sorption
      coefficients (Kd values) than a polydimethylsiloxane (PDMS) coated fiber. Gas
      chromatography-flame ionization detection (GC-FID) detection limits with the CW
      DVB sorbent are approximately 0.5 to 10 ng/ml in a 2-ml water sample for a
      variety of aromatic amines, phenols, and chlorinated phenols, and are
      approximately 1 to 50 ng/ml for the same solutes using the PA sorbent. However,
      the PA fiber is more selective (depending on the water pH) for the acid or base
      components than the CW-DVB fiber. With proper pH adjustment, the recovery of
      spiked aromatic amines and phenols from a surface wetlands water ranged from 73
      to 118% of the known values, with a precision (R.S.D.) of approximately 5 to 20%.
      SPME quantitation of phenols in a coal gasification wastewater using a PA fiber
      also gave excellent agreement with conventional methylene chloride extraction,
      although continued use of a single fiber with this wastewater led to poorer
      precision.

PMID- 9923083
TI  - Levels of metamidophos in air and vegetables after greenhouse applications by gas
      chromatography.
AB  - The diminution of metamidophos residue levels with time in vegetables an
      greenhouse air was investigated after treatment of tomatoes and green beans. A
      gas chromatographic method using dichloromethane as an extraction solvent has
      been developed to analyse metamidophos in vegetables, with obtained recoveries
      higher than 89%. The reliability of several sorbents for air sampling was tested
      using standard atmospheres resulting in recoveries higher than 90% from PUF, XAD
      2, XAD-4 and Supelpak using Soxhlet extraction with acetone. The dissipation of
      metamidophos in greenhouse air was studied 52 h after application. Finally the
      effect of crop, type of greenhouse, season and dose applied on the dissipation
      kinetic of metamidophos in vegetables, was statisTically studied by analysis of
      variance resulting in crop and season being the most significant factors.

PMID- 9923084
TI  - Solid-phase microextraction applied to the analysis of pesticide residues in
      honey using gas chromatography with electron-capture detection.
AB  - The possibilities of using solid-phase microextraction to determine residues of
      pesticides in honey have been examined. For this purpose, three types of fiber
      have been assayed: polyacrylate of 85 microns thickness, and polydimethylsiloxane
      of 7 and 100 microns thickness. They have been applied to the extraction of 21
      pesticides of different chemical families. The effects of the temperature,
      extraction time and ionic strength on the microextraction have been studied,
      proposing the most adequate for each fiber. Under optimized conditions,
      precision, intervals of linearity and detection limits were evaluated.

PMID- 9923085
TI  - Fluorescence detection of proteins and amino acids in capillary electrophoresis
      using a post-column sheath flow reactor.
AB  - A simple laser-induced fluorescence detection method for proteins and amino acids
      in capillary electrophoresis is reported. A sheath flow cell is utilized as a
      post-column reactor for fluorescence derivatization of proteins and amino acids
      by addition of o-phthaldialdehyde-2-mercaptoethanol to the sheath fluid. With the
      use of a 50 microns I.D. capillary, the limits of detection for carbonic
      anhydrase are 0.73 nM or 1.8 amol which represents a five- and two-fold
      improvement, respectively, over the best results previously reported for post
      column detection. In addition, separation efficiencies up to 8.07 x 10(5) are
      achieved and the detector response is linear over three-orders of magnitude.
      These results demonstrate that mixing is adequate and the reaction kinetics are
      rapid enough to provide sensitive detection with this approach. Also, because
      this post-column derivatization scheme requires no instrumental changes to a
      typical sheath flow cell detector, the system can be used for detection of pre
      column labeled analytes and for native fluorescence detection.

PMID- 9923086
TI  - Determination of chlorinated acid herbicides and related compounds in water by
      capillary electrophoresis-electrospray negative ion mass spectrometry.
AB  - Capillary electrophoresis electrospray negative ion mass spectrometry was
      investigated for the determination of chlorinated acid herbicides and several
      phenols in water. Sixteen analytes were separated as their anions in less than 40
      min with a buffer consisting of 5 mM ammonium acetate in isopropanol-water
      (40:60, v/v) at pH 10. A sample stacking technique was used to provide lower
      detection limits and a fortified drinking water sample was made pH 10 and
      analyzed without further processing. Quantitative analyses with an internal
      standard gave recoveries in the 91-124% range and replicate measurements of a
      calibration standard gave relative standard deviations in the range of 3-10%.

PMID- 9923087
TI  - Simultaneous determination of inorganic anions and cations in waters by capillary
      electrophoresis.
AB  - The applicability of a recently proposed capillary electrophoresis technique
      based on the electromigrative sample introduction from both ends of the capillary
      was further investigated for the simultaneous determination of inorganic anions
      and cations in real water samples. The optimized separations were carried out in
      5.0 mmol l-1 copper(II)-ethylenediaminehydroxide and 2.0 mmol l-1 triethanolamine
      electrolyte neutralized with chromic acid to pH 8.0, using indirect UV detection
      at 254 nm. Nine inorganic ions (Cl-, NO3-, SO4(2-), HCO3-, K+, NH4+, Na+, Ca2+
      and Mg2+) were well separated in less than 5 min. The analytical performance of
      the method is discussed in terms of migration time, peak area and corrected peak
      area repeatability, linearity of response and detection limits. To evaluate this
      system, the determination of anions and cations was examined for mineral water,
      tap water and river water samples using Li+ as the internal standard. The
      comparison of the results with ion chromatography and conventional capillary
      electrophoresis is presented.

PMID- 9923088
TI  - Up to date treatment of hepatitis C in adults.

PMID- 9923089
TI  - Meal-related changes in plasma CCK bioactivity in patients with chronic
      pancreatitis.
AB  - In order to clarify whether there is a negative feedback mechanism for CCK
      secretion, we investigated plasma CCK bioactivity in patients suffering from
      chronic pancreatitis (CP) according to the characteristics of their pancreatic
      disease. Basal, meal-stimulated, and integrated release of plasma cholecystokinin
      (CCK) bioactivity was measured in 24 patients with CP and in 12 healthy controls.
      The values obtained were compared between the healthy control group and the CP
      group, and between subgroups of CP patients established on the basis of the
      presence/absence of several parameters: abnormal gastric emptying, abdominal
      pain, steatorrhea, pancreatic calcification, insulin-requiring diabetes mellitus,
      and impairment of pancreatic exocrine functions as indicated by secretin test. A
      bioassay method using pancreatic acini was used to measure plasma CCK
      bioactivity. In the control group, plasma CCK bioactivity increased from a basal
      value of 1.6 +/- 0.7 pmol/L to a maximal increase of 6.6 +/- 4.1 pmol/L, and the
      integrated CCK release following a test meal was 37.7 +/- 19.3 pmol/L.150 min. In
      the CP group, plasma CCK bioactivity increased from 1.6 +/- 0.9 pmol/L to a
      maximal increase of 8.2 +/- 8.7 pmol/L, and the integrated release of CCK was
      43.0 +/- 37.7 pmol/L.150 min. None of the differences between them were
      significant. No significant differences in basal value, maximal increase, or
      integrated plasma CCK release were noted according to any of the parameters of
      the CP patients and the control group. Nor was there any correlation between
      impairment of pancreatic exocrine function and plasma CCK bioactivity. These
      results provide no evidence of a negative feedback mechanism between pancreatic
      exocrine dysfunction and CCK secretion.

PMID- 9923090
TI  - Prolactin and colorectal cancer: is there a connection?
AB  - The purpose of this study was to confirm the reported incidence of
      hyperprolactinemia in colorectal cancer and to find further evidence for an
      ectopic prolactin production by the tumor. MATERIAL AND METHOD: Thirty two
      consecutive patients with an adenocarcinoma of the colon (n = 17) or the rectum
      (n = 15) were included. Preoperative serum prolactin concentrations were
      determined and correlated with CEA concentrations and tumor stages. To exclude an
      ectopic production by the colon cancer, prolactin concentrations were determined
      during the operation, in the peripheral blood and in the efferent venous drainage
      area of the tumor. After resection, immunohistochemical staining for prolactin
      was made in all resected tumors. RESULTS: In all except two patients with a
      rectal cancer, preoperative plasma prolactin concentrations were normal.
      Peroperative serum concentrations of prolactin were high in all patients. No
      significant gradient was found between the peripheral venous concentration and
      the local venous concentration in the drainage area of the tumor.
      Immunohistochemical staining for prolactin was positive in only one rectal
      cancer. Finally, no correlation was found between plasma prolactin concentrations
      and tumor stages or CEA concentrations. CONCLUSION: Our results do not support
      the hypothesis of an ectopic prolactin production by colon adenocarcinoma. Only
      in a subgroup of rectal cancers, an ectopic prolactin production remains
      probable. At present, prolactin cannot be recommended as a tumor marker in
      colorectal cancer.

PMID- 9923091
TI  - Incidence of inflammatory bowel disease in the area of Liege: a 3 years
      prospective study (1993-1996).
AB  - A first prospective epidemiological study of IBD was conducted in the area of
      Liege. The duration of the study was short taking into account the small size of
      the population (1 million inhabitants). Therefore we carried out a 3 years
      prospective study. METHOD: Private and public gastroenterologists completed a
      questionnaire for each new case they diagnosed between 01.06.1993 and 31.05.1996.
      RESULTS: During that period 270 IBD patients were identified: 137 (51%) had
      Crohn's disease (CD), 111 (41%) had ulcerative colitis (UC) including 32
      proctitis (29% of UC) and 22 (8%) had unclassified colitis. The mean annual
      incidence per 10(5) was 4.5 for CD and 3.6 for UC. The female/male ratio was 1,6
      for CD and 0,5 for UC. The median age at the time of diagnosis was 30 years for
      CD and 39 years for UC. The mean time between the onset of symptoms and the
      diagnosis was 6,5 months for CD and only 4,8 months for UC. Family history of IBD
      was found in 15% of patients with CD and in 7% of UC. CONCLUSIONS: These data
      show a high incidence of IBD in the area of Liege. These results confirm those
      reported during the first year of the prospective study which were similar to
      those observed in North-western France. Contrary to the other countries of
      Northern Europe, the incidence of UC is lower than the one of CD. Belgium appears
      to be a privileged country to undertake a national register and to study
      epidemiological aspects of IBD.

PMID- 9923092
TI  - A methodology for consensus conferences. Societe Royale Belge de Gastro
      enterologie.
AB  - Consensus conference is one of the methods proposed to develop clinical practice
      guidelines. This method is used when the topic is limited to a small numbers of
      questions (4 to 6) and when there is a controversy. This process is based on the
      meeting of a jury which reviews the scientific information provided by the
      literature and presented by experts. The consensus conference consists of three
      phases: A preliminary phase during which questions are well defined, experts and
      jury are chosen by a panel of organizers usually designed by scientific
      societies. In the jury there are multidisciplinary specialists, generalists
      practitioners and other people such as nurses, economists, ... Experts conduct
      the review and analysis of the literature. The jury is informed by organizers
      about the methodology of a consensus conference and about the quality of
      scientific information available. The second phase is the plenary session of the
      consensus conference. It lasts one or two days during which the expert's texts
      and presentation are discussed by the jury and a public. The third phase is the
      actual meeting of the jury, behind closed doors, during which conclusions and
      clinical practice guidelines are formulated. Dissemination of these guidelines is
      one of the major factors determining the impact of the consensus conference.
      These guidelines are usually mailed directly to the professionals concerned and
      published in scientific journals and dissiminated via professional associations,
      universities, post graduate training bodies, ... The impact of the conference is
      assessed one or two years after and compared by the same method with the results
      of a preliminary survey before the conference. This process is long and expensive
      but is increasingly used because of the necessity for physicians to assimilate
      and to integrate into their daily clinical practice an increasing mass of
      scientific information.

PMID- 9923093
TI  - Is automatic disinfection between each endoscopy mandatory? Societe Royale Belge
      de Gastro-enterologie.

PMID- 9923094
TI  - Is antiviral treatment (IFN alpha and/or ribavirin) justified in cirrhosis
      related to hepatitis C virus? Societe Royale Belge de Gastro-enterologie.
AB  - AIM: To assess the benefit risk ratio of interferon and ribavirin in the
      treatment of patients with post hepatitis C cirrhosis we summarize the
      spontaneous over mortality of this disease, and made an overview of the
      randomized trials and of other controlled studies. RESULTS: In comparison to
      controls, patients with post hepatitis C cirrhosis have a 17 fold increase risk
      of dying from a liver disease that a control population, and a 6 fold increase
      from primary liver cancer. In France the hepatitis C epidemic which start in the
      sixties explains now the observed dramatic increase in mortality by primary liver
      cancer, both in men and women. Meta-analysis of randomized trials and controlled
      retrospective studies showed that interferon treatment is associated with a
      significant increase in ALT response at the end of the treatment, with a decrease
      in hepatocellular incidence as well as a decrease in mortality in comparison with
      controls. Very few data are published concerning ribavirin alone or in
      combination with interferon in patients with cirrhosis. Preliminary data suggest
      that this combination during 48 weeks permit to obtain in patients with
      compensated cirrhosis 20% of sustained virological response. The safety was
      acceptable but patients with low initial blood cells count must be carefully
      followed. In conclusion this overview clearly demonstrates a benefit-risk ratio
      in favor of treatment in patients with post hepatitis C cirrhosis by interferon.

PMID- 9923095
TI  - Is it justified to give antisecretory drugs before an endoscopy in case of
      symptoms suggestive of gastro-oesophageal reflux disease? Societe Royale Belge de
      Gastro-enterolgie.

PMID- 9923096
TI  - Is surgery the treatment of choice for long term control of gastro-esophageal
      reflux disease?Societe Royale Belge de Gastro-enterolgie.

PMID- 9923097
TI  - Results of the GLEM/LOK survey in Belgium.

PMID- 9923098
TI  - Gastrointestinal decontamination in acute toxic ingestions.

PMID- 9923099
TI  - Acute hepatitis due to poisoning.

PMID- 9923100
TI  - Gastric motor and sensory function testing.

PMID- 9923101
TI  - Non ulcer dyspepsia and Helicobacter pylori.

PMID- 9923102
TI  - Malt lymphoma as first clinical presentation of a celiac disease.
AB  - We report a case of a 35 year-old-woman who suffered from abdominal pain and
      weight loss. Asymptomatic celiac disease was discovered and complicated with a
      MALT Lymphoma in the jejunum. This is an uncommon combination because lymphoma
      that arises in the presence of enteropathy is commonly from T lymphocytes. Also
      because it normally appears in patients with long standing celiac disease who
      report a recrudescence of the abdominal symptoms.

PMID- 9923103
TI  - A case of hairy cell leukemia resembling asymptomatic chronic liver disease on
      presentation.
AB  - Hepatic infiltration in hairy cell leukemia is quite common but results of liver
      test are usually normal. A 44-year-old man with a history of alcohol abuse was
      evaluated for persistent elevation in serum aminotransferases. A percutaneous
      liver biopsy showed an extensive mononuclear cell infiltrate in the sinusoids and
      this finding led to the diagnosis of hairy cell leukemia. Liver involvement in
      hairy cell leukemia is discussed. Hairy cell leukemia should be considered as a
      potential cause of persistent increase in liver-related enzymes.

PMID- 9923104
TI  - Intramural haematoma of the duodenum: a rare cause of duodenal obstruction.
AB  - Intramural haematoma is a rare cause of duodenal obstruction. Its most common
      cause is abdominal trauma. Diagnostic difficulty arises if the patient or the
      child's parents fail to mention the episode of trauma, regarding it as an
      unrelated or insignificant event, as in the presented case. Computed tomography
      is the imaging modality of choice. Intramural duodenal haematoma is best treated
      conservatively, since operative treatment is associated with a high complication
      rate and longer hospitalization.

PMID- 9923105
TI  - The use of microplates in the treatment of dento-alveolar fractures. A case
      report.
AB  - A case of a women is presented who was treated successfully with microplates for
      a dento-alveolar fracture of the mandible.

PMID- 9923106
TI  - [Temporomandibular joint prosthesis. A retrospective study from 1947].
AB  - Degenerative troubles of the temporo-mandibular joint constitute a major
      pathology for the maxillo-facial surgeon. While articular replacements have long
      been developed and used by orthopedic surgeons, none of these seem to give
      satisfaction in the TMJ. After a short historical and physiological recall, a
      number of techniques are described, together with a short evaluation of their
      use. In all 597 cases are reported, whilst an attempt at classification is made
      in the different types of prostheses used, ie interpositional, endo-osseous,
      extra-cortical, and prostheses designed for extensive reconstruction.

PMID- 9923108
TI  - Cervical metastases from pulmonary epidermoid carcinoma.
AB  - A patient with a right latero-cervical swelling of three-months history was
      observed. Fine needle aspiration biopsy showed the presence of metastases of
      epidermoid carcinoma moderately differentiated. No signs or symptoms of head and
      neck neoplasm were presents. After instrumental evaluation the primary neoplasm
      was localised at the left lung and metastases were also localised in the right
      submandibular gland. Although metastases from pulmonary epidermoid carcinoma are
      normally bloodborne, in this case lymphatic metastases involving cervical areas
      were present, probably secondarily the submandibular involvement.

PMID- 9923107
TI  - Comparative study of AgNOR and PCNA in experimental carcinogenesis of salivary
      glands of rats.
AB  - Previous studies regarding experimental carcinogenesis demonstrated that
      submaxillar glands (GSM) submitted to DMBA present cellular modifications of
      progressive gravity in different periods after eight days of the experiment (J.
      Dent. Res 59: 1067, 1980). This current work pursues the objective of
      determining, quantitatively, regions of nucleolar organizations (AgNOR) and
      immunomarkation of the antigen of nuclear proliferation (PCNA) for their possible
      link with the morphostructural findings previously described. By means of
      argentic impregnation, the AgNOR were identified. The histometric was performed
      according to the numeric parameters of AgNOR per nucleus (CABRINI et al. 1992)
      immersed 1000x. A triple blind reading of the five randomly chosen studies from
      each of the twenty cases studies with distinct experimentation stages was
      completed. The results were compared to the normal areas (control group). The
      PCNA was determined immunohistochemically (Avidina-Biotina System Dako). The
      average number of AgNOR was 11 after eight days; 16 after fifteen days and 12
      after twenty days of the experiment (100% adenocarcinoma). In the control group,
      the average number of AgNOR did not exceed 6. The PCNA after eight days was
      negative. The reaction in the tumor area was between 20 and 30% positive. The
      results indicate an increase in the number of AgNOR in relation to the neoplastic
      proliferation, corroborated by PCNA immunodetection.

PMID- 9923109
TI  - [Informed consent: myth or reality?].
AB  - The right to give or withhold free an informed consent is considered in detail,
      historically, ethically and guidelines are suggested for the practitioner.

PMID- 9923110
TI  - [Y chromosome microdeletions in male infertility].

PMID- 9923111
TI  - [Treatment of sexually transmitted diseases].

PMID- 9923113
TI  - [Classification of endometriosis: history and perspective].

PMID- 9923114
TI  - [Current epidemiology of vulvar cancer].
AB  - Cancer of the vulva is a rare disease accounting for only 3 to 5% of all
      gynaecologic cancers. The incidence rates of this cancer vary depending upon the
      country considered, the lowest rates being reported for Asian and African
      populations. An increased incidence of in situ carcinomas of the vulva has been
      noted recently among young women. In this population, the risk factors are: a
      young age at first sexual intercourse, multiple sexual partners, a low socio
      cultural level, previous infection by human papilloma virus (HPV) and smoking. An
      association has also been found with other types of cancers, either in relation
      with HPV-infection or with tobacco use. In contrast, older women are usually
      diagnosed with advanced-stage, squamous or keratinous invasive forms of the
      disease with no clear link with either smoking experience or previous HPV
      infection.

PMID- 9923112
TI  - [Contraceptive use in female transplant recipients].
AB  - The choice of a good contraception is difficult in allograft recipient woman.
      Even if patients recovered a normal menstruation and fertility, the oral and the
      intra-uterine devices contraceptives are contraindicated. If pregnancy occur too
      soon after the transplantation, the survival graft is in danger. According to the
      literature, 50% allograft recipient have begun a pregnancy without medical
      concentration. In this article, we wanted to find the contraceptive method
      effective and appropriate in recent allograft recipient female according to the
      organ grafted. We discuss the new contraceptive methods and advise to avoid, in
      first instance a tubal ligature.

PMID- 9923115
TI  - [Value of peritoneal cytology after hysteroscopy in endometrial adenocarcinoma
      stage I].
AB  - Nineteen clinical stage I adenocarcinoma of the uterus with favourable
      histological prognosis factors (low grade, no myometrial extension, and no pelvic
      node involvement) were diagnosed using a preoperative hysteroscopy. During the
      laparotomy, a peritoneal cytology was performed systematically. The frequency of
      positive peritoneal washings was abnormally high (7 cases) with cytologic
      findings showing grouped cells in large clusters. However, these patients have
      not experienced peritoneal recurrences. The endoscopic procedures may have
      facilitated the transtubal malignant cell dissemination and are questionable in
      front of endometrial carcinoma.

PMID- 9923116
TI  - [Pelvic trauma and pregnancy. Literature review and case report].
AB  - The authors are dealing with a case of a pelvic fracture (right superior pubic
      ramus) after a road traffic accident to a patient who arise a pregnancy with
      twins at twenty five weeks pregnant. Seven per cent of a road traffic accident
      affect pregnancy with a maternal death rate from eight to sixteen per cent and a
      fetal death rate up to fifty seven per cent. Pelvic trauma are more deleterious
      during the pregnancy because of the gravide uterus, of the abdominal injuries
      binding more often, and of pregnancy secondary maternal physiology which lead to
      delay diagnosis and therapeutics. Blunt fetomaternal consequences are ruled by
      pelvic haematomas, uterine rupture, prematurity, acute fetal distress, fetal
      injuries and in utero death. At mid and long range arise the problem of child
      birth way and the risk of mechanical dystocy. Cesarean is store in case of
      vesical and urethral injuries, or perineal injury, several pelvic fractures or in
      case of the pelvic belt fracture moved and not reduced, bringing to a surgical
      unsymmetrical pelvis. In the other cases, the obstetrical prognoses will be done
      after a dialogue with all medical staff and a full synthesis of the file based on
      the fetopelvic comparisons (obstetrics previous, clinic, fetal biometry,
      pelvimetry X ray).

PMID- 9923117
TI  - [Spontaneous and complete uterine rupture on a scarred gravid uterus].
AB  - Uterine rupture is a complication occurring mostly during labour. Spontaneous
      rupture on gravid uterus is rare. We report the 1st case observed on a scarred
      uterus in 32 week gestation in Gyn/Obs clinique at Dakar University Hospital.
      Favorable factors found were: segmento-corporeal scar time, poor technical
      repair. Then, we pose the problems of follow up of these pregnancy involving
      scarred uterus and discuss the interest of evaluating prognosis of the quality of
      the uterine scar.

PMID- 9923118
TI  - [Simple technic for embryo transfer when the transfer is difficult].

PMID- 9923119
TI  - [The scientific venture of Battista Grassi and the discovery of Anopheles in
      malaria].

PMID- 9923120
TI  - [Radio-surgical-histological procedure in the diagnosis and management of non
      palpable breast lesions, suspected from mammography: experience of "Casa Sollievo
      della Sofferenza" Hospital in San Giovanni Rotondo].
AB  - The almost 4-year long experience of the IRCCS--"Casa Sollievo della Sofferenza"
      hospital (FG, Italy) dealing with 165 nonpalpable breast lesions mammographically
      detected is herein presented. According to a protocol based on the previously as
      well as relatively recent described guidelines for the clinico-pathological
      management of such lesions, the authors underline the necessity of a strict
      cooperation between the radiologist, the surgeon and the pathologist. They also
      emphasize the perspectives derived from such a new impact, among which the most
      impressive is the handling and sampling of this relatively new type of material
      with lesions which only rarely are grossly palpable ("pseudononpalpable
      lesions"), whilst often they are truly non palpable being of minute sizes
      ("microlesions") and even grossly "invisible" ("quasi-normal fibrofatty tissue").
      Of note as consequences derived from the strict adherence to this type of
      protocol which anyone should adhere to there are also a decrease of frozen
      section diagnoses, a global increase in the surgical pathology lab workload, the
      ban for taking away any tissue from the lesion or from the area of concern for
      special studies, the technical approach to the identification of
      microcalcifications when they are present, the new questions & answers concerning
      with the completeness and the adequacy of excision, the state of surgical margins
      of the excised specimens, and the possible existence of residual in situ or
      infiltrating disease. The results herein presented area in consonance with those
      from other institutions so confirming the high incidence both of borderline
      lesions and in situ malignancies (overall incidence around 28%) and of the early
      and minute invasive cancers (44%) usually of favourable histological types, among
      truly nonpalpable breast lesions.

PMID- 9923121
TI  - [Primary cutaneous mucormycosis. A case report].
AB  - One case of primary cutaneous mucormycosis developed in the hospital environment
      is reported. Dressings contaminated by hyphae may have been the cause. In
      diabetic or immunodepressed patients this disease may be fatal. Incisional biopsy
      is the only diagnostic tool.

PMID- 9923122
TI  - [Actinomyces infection in a compound odontoma].
AB  - INTRODUCTION: Compound odontoma is an abnormal development of dental tissue which
      is characterized by regular and ordinate structures that resemble a normal tooth.
      Actinomyces is an abnormal inhabitant of the oral cavity which is able to become
      pathological whenever the specific or non specific defense mechanisms of an
      individual may fail. MATERIALS AND METHODS: Described is a case of 60 years old
      male with no deficit of his immune system confirmed by various analysis. There is
      one year history of an intermittent pain to the left half of his mandible. An x
      ray suggests an odontoma. The gengiva, near the lesion, appears to be ulcerated;
      two fistulous tracts with the oral mucosa and one with the skin area are seen.
      After decalcification the tissue obtained from the lesion has been fixed in
      formalin and included in paraffin. The slides were stained with Haematoxilin
      Eosin, PAS and Grocott's silver method. RESULTS: The lesion consists of well
      differentiated enamel and dentin including a fragment of the pulp featuring the
      typical aspects of compound odontoma. In addition the pulp shows an intense
      infiltration of granulocytes, plasma cells and numerous capillaries; around the
      pulp an extensive area of necrosis is present, in which there are eosinophilic
      aggregates of amorphic and granular matrix suggestive of an infection by
      actinomyces. This was confirmed with PAS and by an intense urgyrophilia.
      CONCLUSION: Described is a case of compound odontoma complicated by an
      actinomycosis infection in a patient with a well functioning immune system which
      appears to be the first case reported in the literature, to the best of our
      knowledge.

PMID- 9923123
TI  - [Primitive angiitis of the central nervous system. An autopsy case report].
AB  - Primary angiitis of the central nervous system (PACNS) is a rare vasculitis
      limited to the leptomeningeal and intraparenchymal vessels. Histologically, the
      angiitis may be granulomatous with giant cells, necrotizing, or lymphocytic in
      character, and mixed morphologic types often occur. It is frequently fatal when
      the diagnosis is performed too late. We describe an autopsy case with multiple
      cerebral infarcts.

PMID- 9923124
TI  - Inflammatory pseudotumor of the liver. Report of two cases.
AB  - Inflammatory pseudotumor (IPT) is a rare lesion of the liver. We report two cases
      of IPT of the liver. Patients were a 32-year-old man and a 45-year-old female.
      Preoperative clinical diagnoses were respectively amebic abscess and metastatic
      tumor. Fine needle aspirations were performed and cytopathologic findings were
      compatible with an inflammatory process in both cases. Simple excision was
      performed in the first case and left lobectomy in the second one. Gross
      examination revealed expansive solid tumoral masses which measured 3 x 2 x 2 cm
      and 7 x 5 x 5 cm, respectively. Both lesions were yellow and firm. On microscopic
      examination, lesions were composed of fascicles of plump spindle cells
      intermingled with a varying number of plasma cells, lymphocytes and histiocytes.
      The spindle cell fascicles also contained a moderate amount of intercellular
      collagen. No microorganism was found on PAS, Giemsa, Grocott and Ziehl Nielsen
      stained sections. Plasma cells were immunoreactive for both kappa and lambda
      light chains, revealing their polyclonal nature. Since hepatocellular carcinoma
      is concerned in differential diagnosis, IPT is of particular clinical importance.
      Despite the limited experience with fine needle aspiration cytology,
      histopathologic diagnosis of IPT does not pose great difficulty.

PMID- 9923125
TI  - [Esophagitis and Barrett's esophagus: minimal diagnostic criteria].

PMID- 9923126
TI  - [Genetics of cutaneous melanoma].

PMID- 9923128
TI  - Getting the numbers right.

PMID- 9923127
TI  - [Posthumous ill-treatment. 1804: Napoleon establishes the pathology museum of
      Bologna....].

PMID- 9923129
TI  - Participate, don't alienate.

PMID- 9923130
TI  - Boom or bust.

PMID- 9923131
TI  - Med Bytes.

PMID- 9923132
TI  - Forum on ethics. Genetics: manipulating mother nature.

PMID- 9923133
TI  - Legislating health.

PMID- 9923134
TI  - Do the right thing.

PMID- 9923135
TI  - Privileges primer.

PMID- 9923136
TI  - Forget fair play.

PMID- 9923137
TI  - Best of both worlds.

PMID- 9923138
TI  - Producing physicians for south Texas.
AB  - South Texas, one of the fastest growing regions in the country, remains among the
      most medically underserved, in part, because few students from South Texas enter
      medical school. To address this issue and to increase the diversity of the
      matriculant pool, Baylor College of Medicine (BCM) and The University of Texas
      Pan American (UT-PA) established in 1994 the Premedical Honors College (PHC), a
      rigorous undergraduate program at UT-PA for students from South Texas high
      schools. Students who complete all PHC requirements and BCM prerequisites are
      accepted into BCM upon graduation from UT-PA. Those in good standing receive
      counseling, enrichment experiences, and tuition and fee waivers from UT-PA and
      BCM. The program is increasing the number of students from South Texas
      universities matriculating into medical school, and is expanding the involvement
      of local physicians in undergraduate education, heightening visibility for
      partner institutions, and becoming an effective, replicable bachelor of
      science/doctor of medicine model.

PMID- 9923139
TI  - Shifting the costs of indigent care back to county governments.
AB  - Despite a decade of steadily rising prosperity, Texans are losing health care
      benefits at an alarming rate. As many as 41 million people in this country, or
      15% of the population, lack health care coverage of any kind. Most of these
      people are under age 65 and are gainfully employed, but their employers don't
      provide coverage and/or don't pay them enough to afford it themselves. Most have
      minimum wage jobs and are ineligible for Medicaid. These individuals plant the
      gardens, work in fine restaurants, clean expensive houses, and generally benefit
      the communities in which they reside. Texas law suggests that county governments
      and property owners should pick up the tab for the medically indigent. However,
      as the uninsured numbers grow, county governments are finding ways to extricate
      their taxpayers and the institutions they support from the obligatory role as
      payer of "last resort" for these people. While reimbursement from government
      programs, managed care, and commercial insurers is putting tremendous financial
      pressure on health care providers, the county systems simply are not assuming
      their financial, legal, or ethical responsibilities for those outside the
      protective cover of these programs. In my experience, health care for the
      medically indigent has become "charity care" at the profit and nonprofit
      hospitals in the state. The strain is palpable in the emergency rooms, where by
      law the medical crises of the poor must be treated. This de facto safety net is
      fraying, and our political leaders need to make the painful decision to raise
      sufficient tax revenues to remove the weight.

PMID- 9923140
TI  - Transplacental transfer of radionuclides. A review.
AB  - Transplacental transfer of tritium (H), cesium (Cs), iodine (I), strontium (Sr)
      and plutonium (Pu) has been observed in all examined species with an active
      transfer mechanism for iodine, strontium and plutonium. Cesium and tritiated
      water freely cross the placenta and are distributed approximately uniformly in
      maternal as well as in fetal tissue. In pregnant mice, 137Cs concentrations in
      maternal organs were 4-6 times higher than in the foetus. With increasing weight,
      Cs amounts rise in the foetus. 131I distribution in the foetus before and after
      the beginning of thyroid function is totally different. In an 8-week-old human
      foetus, there was almost no accumulation of 131I in the thyroid gland, while on
      week 14 of gestation more than 40% of the fetal iodine was accumulated in the
      thyroid gland. Radioiodine given only once results in distinctly higher fetal
      maternal ratios than after long-term exposure. Experiments performed to evaluate
      the extent of placental barrier of Sr in comparison to Ca showed a maximum of
      Sr/Ca discrimination early in pregnancy while at the end of pregnancy Sr and Ca
      are transported to almost equal proportions across the placenta. A well-known
      phenomenon is the accumulation of Pu in the yolk-sack of rats such that 80% of
      the total activity is contained in the feto-placental unit. For the extrapolation
      of results from animals to man, experiments should not be confined to laboratory
      animals but include primates. Furthermore, computer softwares like MIRDOSE could
      be used to simulate transplacental distribution.

PMID- 9923141
TI  - Successful treatment of an equine preputial fibrosarcoma using 5
      fluorouracil/evaluation of the treatment using quantitative PCNA and Ki67 (MIB 1)
      immunostaining. (case report).
AB  - An 18-month-old cross-bred Fjord pony colt presenting a fibrosarcoma of the
      prepuce with severe infiltrative growth, was treated by topical application of 5
      fluorouracil. Biopsies were taken before and after a treatment period of 2
      months. As a control, preputial tissue from a healthy horse was biopsied. Tissue
      sections were stained immunohistochemically for Proliferating Cell Nuclear
      Antigen (PCNA) and Proliferation related factor--Ki67 (MIB1). Using computerized
      quantitative image analysis of these sections, Mitotic index (PCNA), Growth
      Fraction (Ki67) and total nuclear area percentage of the dermis were calculated.
      The Mitotic index, growth fraction and total nuclear area percentage were
      significantly (P < 0.001) reduced at the end of the treatment period compared to
      the initial biopsy tissue, but they still were significantly higher than the
      control values, due to a remnant inflammatory reaction to the cytostatic drug.
      After treatment of the lesion, the pony fully recovered with no visible residual
      lesions on the prepuce. On follow-up 6 months after treatment, the horse showed
      no signs of recurrence. The success of the present treatment should encourage
      further clinical trials in cases of malignant fibrous tumours of skin in horses.
      The quantitative analysis of cell proliferation in biopsies can be used to
      evaluate treatment follow-up.

PMID- 9923142
TI  - Weights and blood profiles of the west African hinge-backed tortoise, Kinixys
      erosa and the desert tortoise, Gopherus agassizii.
AB  - The body weight and blood profile were determined in the adult wild West African
      hinge-backed tortoise, Kinixys erosa and the adult wild desert tortoise, Gopherus
      agassizii kept under identical environmental conditions. A comparison between
      sexes showed the male K. erosa had significantly higher packed cell volume and
      haemoglobin concentration and lower body weight and plasma alkaline phosphatase
      values than the female, while no significant sex differences appeared in these
      parameters in G. agassizii. The haematological parameters and plasma levels of
      electrolytes, enzymes, proteins and metabolites did not differ significantly
      between the two species, suggesting that the blood values of K. erosa resembled
      those of G. agassizii under identical environmental conditions.

PMID- 9923144
TI  - Absorption and excretion of cefquinome in coho salmon (Oncorhynchus kisutch) in
      freshwater at 10 degrees C.
AB  - The absorption and elimination of cefquinome in serum and tissues of coho salmon
      were studied. The study was performed in freshwater at 10 degrees C with fish
      weighing 100 +/- 5 g (mean and standard deviation). Single doses of 5, 10 and 20
      mg/kg were administered intraperitoneally to 30 fish for each dose. The maximum
      concentration occurred in the following order; kidney and liver > serum > muscle
      > brain. The pharmacokinetic analysis and predictive withdrawal times were
      calculated using only the dose of 20 mg/kg body weight. The peak cefquinome
      concentrations (Cmax) in serum (3.35 +/- 0.45 micrograms/ml) and muscle (2.87 +/-
      0.53 micrograms/g) were achieved at 12 h. In the brain, the Cmax was 2.18
      micrograms/g at 6 h. The half-lives (t1/2) in serum, muscle, brain, liver and
      kidney were 20.56, 8.93, 9.35, 113.61 and 119.48 h, respectively. With the
      detection limit of 0.015 microgram/g for the cefquinome, the predicted withdrawal
      time with 95% confidence for muscle tissue was 104.2 h at 10 degrees C for the 20
      mg/kg dose. The results suggest that cefquinome could be efficacious and safe for
      the consumer in treating bacterial diseases of coho salmon in fresh water.
      Nevertheless, future studies are required in order to determine an adequate dose
      with the corresponding withdrawal times.

PMID- 9923143
TI  - Hypomagnesemia and mitral valve prolapse in Cavalier King Charles spaniels.
AB  - There is a high incidence of mitral valve prolapse (MVP), an abnormal
      displacement of one or both mitral valve leaflets during systole, in Cavalier
      King Charles Spaniels (CKCS). In humans, MVP is known to be associated with a low
      magnesium status. In this study, the plasma magnesium concentration was measured
      in 30 CKCS without heart failure. It was also investigated whether MVP-severity
      and degree of regurgitation correlated with plasma magnesium and a number of
      parameters of the renin-angiotensin system, and whether 4 weeks magnesium
      supplementation affected plasma magnesium or the high renin/low aldosterone
      profile associated with MVP. A high prevalence of hypomagnesemia was observed:
      plasma concentrations < 0.70 mmol/l were found in 15 dogs (50%) before and in 12
      dogs (40%) after 4 weeks magnesium supplementation. The mean plasma level was
      0.69 +/- 0.07 mmol/l before and 0.71 +/- 0.07 mmol/l after magnesium (P = 0.22).
      Plasma magnesium concentrations did not correlate with MVP-severity and degree of
      regurgitation. Plasma aldosterone levels correlated negatively with MVP-severity
      and positively with the degree of regurgitation, and serum angiotensin-converting
      enzyme activities correlated negatively with the degree of regurgitation.
      Magnesium supplementation had no effects on renin and aldosterone nor on the
      ratio between the two. In conclusion, many CKCS without heart failure have
      hypomagnesemia whether they are fed supplementary magnesium or not--a finding
      which may be associated with the high prevalence of MVP in this breed. Further
      studies, however, are needed to clarify the role of a low magnesium status in
      canine MVP.

PMID- 9923145
TI  - Inhalation anaesthesia for the castration of piglets: CO2 compared to halothane.
AB  - General anaesthesia with 80% CO2/20% O2 and 5% halothane in O2 (mask induction)
      was compared for castration of 3-4 week-old piglets. One group was castrated
      without anaesthesia. Of the noncastrated control groups one had CO2- and one
      halothane anaesthesia, one breathed room air through the induction system, and
      one was held in castration position. The behaviour to induction and castration
      was assessed, and the cortisol-, ACTH- and beta-endorphin plasma concentrations
      were determined to quantify the stress elicited by anaesthesia, castration and
      handling. Violent struggling and vocalization were elicited by CO2 and
      positioning into the mask induction system while breathing room air; halothane
      induction was quiet. CO2 induced profound surgical anaesthesia; whereas under
      halothane anaesthesia some animals exhibited still a slight reaction to
      castration. Recovery was fast, smooth and quite. Permanent violent struggling and
      vocalization were elicited by castration without anaesthesia. Plasma cortisol was
      not a sensitive tool to judge castration stress. The high ACTH and beta-endorphin
      plasma concentrations elicited by CO2 anaesthesia confirm our clinical
      experience. General anaesthesia is fast and safely induced with CO2 in piglets
      and castration can be performed without any reaction, but with CO2 anaesthesia
      the stress is not reduced.

PMID- 9923146
TI  - Studies on equine lipid metabolism. 1. A fluorometric method for the measurement
      of lipolytic activity in isolated adipocytes of rats and horses.
AB  - A simple and sensitive method for direct and continuous monitoring of free fatty
      acid (FFA) release, by measuring the pH-sensitive change in relative fluorescence
      intensity of seminaphthofluorescein (SNAFL-1) is described. The method was
      designed to use a small number of adipocytes isolated from fat pads of rats and
      biopsy specimens of horses for the detection of decreasing pH in fat cell
      suspensions caused by released FFA into the incubation medium. Species specific
      differences of lipolysis were demonstrated when adipocytes of rats and horses are
      incubated with stimulators or inhibitors of lipolysis. Norepinephrine (NE)
      stimulated lipolysis in fat cells of rats whereas adipocytes of horses showed a
      measurable release of FFA when concomitantly incubated with NE and adenosine
      deaminase (ADA) or NE and 8-Phenyltheophylline (8-PT), respectively). The
      incubation of equine fat cells with NE and ADA did not influence the
      antilipolytic response to insulin. The method described enables micro-scaled in
      vitro studies on lipolytic activity.

PMID- 9923147
TI  - Clinical assessment of adventitious movements.
AB  - Many procedures with variable validity and reliability have been developed in
      research settings to evaluate adventitious movements and related phenomena in
      specific populations, e.g., people with schizophrenia treated with dopamine
      antagonists, but these only provide global assessments or rate specific
      movements. A battery for rating individuals with possible movements disorders in
      a comprehensive way in clinical settings is needed so a protocol to assess
      briefly and thoroughly potential movement disorders was videotaped for five
      prepubertal boys with autistic disorder and severe mental retardation in a
      clinical trial. Utilizing a Movement Assessment Battery, four raters
      independently scored videotapes of 10-16 movements assessments of each of the
      five subjects. Experienced raters attained agreement of 59% to 100% on ratings of
      tardive dyskinesia and 48% to 100% on tics. Hindrances to reliability included
      poor quality of some tapes, high activity of subjects, and fatigue of raters.

PMID- 9923148
TI  - Gender portrayals in telephone books for gay community versus Pacific-Bell Yellow
      Pages.
AB  - Photographic images (N = 2,700) from three 1997 Pacific-Bell Yellow Pages (n =
      1,976) and from three 1996-97 gay, lesbian, and bisexual community telephone
      books (n = 724) were classified into three groups by visible features (definite
      male, definite female, and gender nonspecific). The latter were excluded. The
      proportion of male photographic images was larger in gay community books than in
      Pacific-Bell telephone books.

PMID- 9923149
TI  - The MMPI-2 Gender-role scales as measures of sex-typing.
AB  - The validity of the MMPI-2 Gender-role GM/GF scales as measures of sex-typing was
      examined relative to gender classification using the Personality Attributes
      Questionnaires. Although mean differences by sex were in the expected direction,
      the scales did not distinguish sex-typed, androgynous, and undifferentiated
      subjects. Correlations with the PAQ gender scales provided some support for the
      criterion validity of Gender-role GM scale for both men and women and the Gender
      role GF scale for women.

PMID- 9923150
TI  - Measuring life events in a sample of South African students: comparison of the
      Life Experiences Survey and the Schedule of Recent Experiences.
AB  - This study compared the Life Experiences Survey and the Schedule of Recent
      Experiences for a sample of 213 students. Scores on the Life Experiences Survey
      Negative discriminated between rural and urban students and between African
      language speakers and Afrikaans/English speakers. A small but significant
      correlation between Life Experiences Survey-Negative and scores on the Center for
      Epidemiological Studies-Depression scale was found, while there was no
      correlation between scores on the Schedule of Recent Experiences with depression.
      The Life Experiences Survey-Negative was the only significant predictor of
      Depression scores. The Life Experiences Survey-Negative interacted significantly
      with all the measures of social support (Friends, Family, Satisfaction, and
      Number of Supports) in predicting depression, while the Schedule of Recent
      Experiences only interacted significantly with support from Family and Number of
      Supports. The study also provides support for clearly distinguishing between
      desirable and undesirable events, since positive events moderated the correlation
      of negative events with depression. The Life Experiences Survey is a more
      promising measure of life events than the Schedule of Recent Experiences in the
      South African context.

PMID- 9923151
TI  - HIV/AIDS prevention through changing risky sexual behavior among heterosexual
      college students: a 1990's bibliography.
AB  - This paper's supplement provides a noncritically evaluated listing of 126
      references concerning AIDS prevention among college students. College counselors'
      and other mental health workers' access to information can be facilitated through
      a bibliography of relevant literature regarding approaches and their
      effectiveness in changing risky sexual behaviors.

PMID- 9923153
TI  - Psychological symptoms of art students seeking psychotherapy.
AB  - Descriptive data concerning type and severity of psychological symptoms of 162
      art students seeking psychotherapy at an art school counseling service were
      obtained. These undergraduate and graduate students who presented for consecutive
      intakes over one year completed the Symptom Checklist-90-R. Women reported more
      severe symptomatology than men. Eighty-six and four-tenths percent of this sample
      met the criteria for probable psychological disorder. The data demonstrate the
      importance for mental health professionals who work with developing artists to
      provide skilled evaluation and treatment for a wide range of psychological
      disorders, to engage in crisis intervention and consultation and to develop a
      strong referral network for management of medication, long-term treatment, and
      hospitalization when necessary.

PMID- 9923152
TI  - The relationship of coping style to dysphoria, anxiety, and anger.
AB  - This study examines Problem-focused Coping and Emotion-focused Coping, as
      measured by the Revised Ways of Coping Checklist, in relation to Dysphoria,
      Anxiety, Anger, Social Support, and course grades in psychology. Women university
      students (N = 245) were assessed two times six weeks apart. Problem-focused
      Coping was significantly negatively correlated with scores on the Center for
      Epidemiological Studies-Depression scale and with scores on the Self-rating
      Anxiety Scale at both time periods. Emotion-focused Coping was significantly
      positively correlated with scores on these scales and with scores on the State
      Trait Anger scale at both times. Emotion-focused Coping was significantly
      negatively correlated with scores on the Social Support Questionnaire at both
      times and significantly negatively correlated with grades.

PMID- 9923154
TI  - Predictors of scores on the Brief Symptom Inventory for ethnically diverse female
      clients.
AB  - Predictors of Brief Symptom Inventory scores were identified for an ethnically
      diverse group of 60 female psychiatric outpatients, with a modal diagnosis of
      mood disorder. Ethnicity, as well as other variables, were meaningful predictors
      on the Somatic, Phobia, and Positive Symptom Total scales. Mexican- and African
      Americans scored higher than Euro-Americans on these scales. Implications for
      using this measure with diverse clients in similar settings are discussed.

PMID- 9923155
TI  - Authoritarian and socially restrictive attitudes toward mental patients in mental
      health volunteers and nonvolunteers.
AB  - 31 French-Canadian mental health volunteers and 43 nonvolunteers participated in
      a study of the relationship between Authoritarian and Socially Restrictive
      attitudes toward mental patients and the variables of volunteer status, age, sex,
      education, having a mentally ill family member, Locus of Control, Extraversion,
      Psychoticism, Neuroticism, and Social Desirability. Bivariate and partial (Social
      Desirability effects removed) correlations suggested that scores on Authoritarian
      and Socially Restrictive attitudes are higher among older, less educated, less
      extraverted men and women who are not volunteers. Although volunteers compared to
      nonvolunteers had lower scores on Authoritarian and Socially Restrictive
      attitudes, they did not differ in terms of age, having a mentally ill family
      member or scores on Locus of Control, Extraversion, Psychoticism, Neuroticism,
      and Social Desirability; however, volunteers were better educated.

PMID- 9923156
TI  - Relation of tolerance of ambiguity to global and specific paranormal experience.
AB  - We examined the relationship of tolerance of ambiguity to severe global factors
      and specific types of anomalous or paranormal experience. 107 undergraduate
      students completed MacDonald's 1970 AT-20 and the Anomalous Experiences Inventory
      of Kumar, Pekala, and Gallagher. Scores on the five subscales of the Anomalous
      Experiences Inventory correlated differently with tolerance of ambiguity. Global
      paranormal beliefs, abilities, experiences, and drug use were positively
      associated with tolerance of ambiguity, whereas a fear of paranormal experience
      showed a negative relation. The specific types of anomalous experiences that
      correlated with tolerance of ambiguity often involved internal or physiological
      experience, e.g., precognitive dreams, memories of reincarnation, visual
      apparitions, and vestibular alterations. We generally found no effects of age of
      sex. These results are consistent with the idea that some paranormal experiences
      are misattributions of internal experience to external ('paranormal') sources, a
      process analogous to mechanisms underpinning delusions and hallucinations.

PMID- 9923157
TI  - The Schreber case: a reinterpretation from an adult-developmental perspective.
AB  - Previous interpretations of the Schreber case have tended to focus on childhood
      factors which led to Schreber's delusional breakdowns, while ignoring the role of
      adult-developmental issues. In the current paper, a multicausal view is taken,
      considering childhood factors (e.g., being raised by an authoritarian father),
      psychosocial experiences (e.g., the failure to have children and the accompanying
      stress), and adult developmental issues (e.g., the psychological and moral
      challenges involved in assuming the position of judge in a high court) that,
      along with a biological predisposition--played a role in Schreber's mental
      illness. Within the context of this larger view of Schreber's life, it is then
      possible to understand better Schreber's own view--that being changed into a
      woman for God to create a new bread of men--was a solution to his psychological
      situation. This solution, however, is highly symbolic, concrete, and does not
      represent development but, rather, avoidance and a kind of regression. It is
      argued that the introduction of adult-developmental issues in this case allows
      for a more complete understanding of the case. The current account also
      represents an attempt to provide understanding while remaining true to the
      phenomenological experience of Schreber.

PMID- 9923158
TI  - Pragmatic language behaviors of adults diagnosed with chronic schizophrenia.
AB  - 35 adults diagnosed with schizophrenia provided samples of narrative and
      conversational discourse and completed a criterion-referenced test of pragmatic
      language ability. There was a significant relationship between performance on
      pragmatic language tasks and perceived over-all functioning of schizophrenic
      subjects as measured by psychological assessment. Subjects who were perceived as
      functioning at low levels on the Global Assessment of Functioning Scale from the
      Diagnostic and 1994 Statistical Manual of Mental Disorders had low self
      disclosure in conversation, produced less information in narratives, and produced
      more nonscorable items on a criterion-referenced test of pragmatic language.
      Appropriateness of speech suprasegmentals was also related to patients' perceived
      effectiveness as communicators as well as to their perceived over-all functioning
      as measured by the Global Assessment of Functioning Scale.

PMID- 9923159
TI  - Does homosexual activity shorten life?
AB  - Previous estimates from obituaries and pre-1994 sex surveys suggested that the
      median age of death for homosexuals is less than 50 yr. Four contemporary
      databases were used to test that estimate: (1) obituaries in the homosexual press
      from 1993 through 1997 reflected treatment success for those with AIDS but
      suggested a median age of death less than 50 years; (2) two large random
      sexuality surveys in 1994--one in the USA and the other in Britain--yielded
      results consistent with a median age of death for homosexuals of less than 50
      years; (3) the median age of those ever married in Denmark, Sweden, and Norway
      was about 50 years, while that of the ever homosexually partnered was about 40
      yr; further, the married were about 5 times more apt to be old and 4 times less
      apt to be widowed young; and (4) intravenous drug abusers and homosexuals taking
      HIV tests in Colorado had almost identical age distributions. The four lines of
      evidence were consistent with previous findings suggesting that homosexual
      activity may be associated with a lifespan shortened by 20 to 30 years.

PMID- 9923161
TI  - Testing Durkheim's theory of suicide in Hungary.
AB  - Measures of domestic social integration which have been found to account for the
      time-series suicide rate in Hungary quite well also accounted for the time-series
      suicide rates of each province and for villages, towns, and cities.

PMID- 9923160
TI  - Correlates of family competence in families with paternal alcohol abuse.
AB  - The present study explored factors correlated with family competence in families
      with paternal alcohol abuse (N = 20). Family competence is measured by the Family
      Competence Scale in the Beavers Systems Model of Family Functioning. Based on a
      review of the literature, socioeconomic status, parents' psychological symptoms,
      and drinking behaviour were selected as possible correlates of family competence.
      The findings indicated that family competence was correlated with both parents'
      reports of psychological symptoms as measured by SCL-90. The strongest correlate
      of family competence was, however, the socioeconomic status of the family. The
      only aspect of drinking behaviour significantly correlated with family competence
      was severity of the fathers' alcohol abuse. These results indicate the importance
      of including individual factors, family factors, and socioeconomic measures in
      the assessment of families with paternal alcohol abuse.

PMID- 9923162
TI  - Confirmatory factor analysis of the Computer Hassles Scale.
AB  - The objective of this research was to determine the latent structure of the
      Computer Hassles Scale using confirmatory factor analysis. This study employed a
      normative database of 1199 student computer users. Both a priori and a posteriori
      latent structure models were tested using LISREL. The analyses did not support a
      latent structure of the scale based on the scale's original two-factor
      definition. Using various goodness-of-fit indices, a four-factor model was the
      best fit.

PMID- 9923163
TI  - Black South African students' beliefs and attitudes about condoms.
AB  - To investigate the beliefs and attitudes of black South African students
      regarding condoms structured questionnaires were completed anonymously by 1986
      students. Most highly endorsed problems were the large number needed for many
      rounds of sex, partner's feelings of distrust, unpleasantness of purchasing
      condoms, and that condoms injure the vagina. Encouragement of use should be
      responsive to local practices.

PMID- 9923164
TI  - Psychopathological dimensions and lack of insight in schizophrenia.
AB  - The present study investigated the relationships of psychopathological dimensions
      of schizophrenia with Insight in a sample of 100 acute schizophrenic patients.
      Lack of insight was significantly correlated with disorganized, excited and
      negative schizophrenic dimensions but not with other Positive and Negative
      Syndrome Scale dimensions. In addition, when insight was assessed through a
      multidimensional approach, a variety of relationships with the schizophrenic
      dimensions were found.

PMID- 9923165
TI  - Sex differences over age groups in self-posed smiling in photographs.
AB  - The present study was designed to investigate self-posed smiling behavior in
      photographs as a function of both sex and age. The photographs of 1,171 Brazilian
      middle-class people, taken in a wide variety of informal social settings were
      examined. Only 25.7% of the girls and 25.0% of the boys of 2- to 5-yrs-age group
      were seen smiling in the photographs. Older children, adolescents, and adults
      were much more expressive than young children. Furthermore, significantly more
      females were seen smiling than males. Females also smiled more expansively than
      males. Finally, smiling was less frequent among middle-aged and older groups,
      especially among males. The present study replicated the sex difference in self
      posed smiling behavior consistently reported by American researchers examining
      college yearbook photographs. Further, the results are consistent with the
      hypothesis that, besides being associated with emotional experience, smiling has
      a strong social motivation.

PMID- 9923166
TI  - Betrayal trauma in adolescent inpatients.
AB  - For 34 hospitalized adolescents sexual distress was associated with histories of
      abuse by family members as compared to nonabuse or abuse by others, while
      posttraumatic stress was not.

PMID- 9923167
TI  - Dimensions of the Center of Epidemiological Studies-Depression Scale for people
      with arthritis from the UK.
AB  - The aim of this study was to investigate the factor structure and to conduct an
      item analysis of the Center for Epidemiological Studies-Depression Scale (CES-D)
      among people with arthritis from the UK. This 20-item self-report scale was
      designed by Radloff in 1977 to measure depressive symptomatology in the general
      population. Data were drawn from a national study and collected through self
      administered questionnaires mailed to participants, each of whom had a confirmed
      diagnosis of arthritis. Reliability and structure of the scale were examined
      using standard item analysis, internal consistency (Cronbach alpha), and
      principal components analysis. A four-dimensional structure was identified: Self
      worth, Depressed Affect, Positive Affect, and Somatic Disturbance; three items
      loaded on two factors and were excluded from consideration. Comparisons with
      previous studies indicated some differences in the subscales and showed that, in
      this sample, two subscales might be artifacts of measurement. In samples of
      people with arthritis from the UK, use of the total score may not reflect
      accurate depressive symptomatology and the subscale scores should be used with
      caution.

PMID- 9923168
TI  - Clarity of instruction by type-A scoring college teachers.
AB  - In a study of 149 college teachers, their self-reported Type-A scores were
      significantly and positively correlated with their perceived clarity of classroom
      instruction.

PMID- 9923169
TI  - Consistency of felons' written and oral responses for scoring the Environmental
      Deprivation Scale.
AB  - 32 male parolees and probationers were administered the questionnaire form of the
      Environmental Deprivation Scale followed by the standard oral interview for the
      purpose of comparing written responses with oral responses usually necessary to
      score the scale. Pearson correlations were .89 between written and oral responses
      and .97 for rater-rater agreement for scoring the questionnaire form. These
      results suggest that a reliable score for the scale can be obtained from an
      antisocial population without the extensive training and time required to
      administer behavioral interviews. Therefore, substituting group testing in place
      of one-on-one interviews may broaden the utility of the scale.

PMID- 9923170
TI  - Note on Tekman's study of preference judgments for excerpts of music.
AB  - Tekman's study is a useful exploration and benefits from his consideration of
      published research on music; however, his interpretation of music tempo research
      by LeBlanc and associates cannot be supported. It would be worthwhile for Tekman
      to conduct a follow-up study with a larger number of participants and music
      excerpts from other styles of music in addition to art music ("classical" music).

PMID- 9923171
TI  - Depersonalization in kindergarten teachers in relation to rejection of help by
      fellow teachers and emotional support from family.
AB  - The present study investigated the external validity of a model describing the
      reactions of spurned helpers by examining the relation of spurning with burnout
      among kindergarten teachers. A second objective was to explore whether emotional
      support from one's family could reduce the negative effects of feeling spurned on
      burnout. 48 kindergarten teachers in Macau responded to a questionnaire measuring
      feeling spurned, emotional support from family, and depersonalization. Analyses
      indicated the effects of feeling spurned on depersonalization and also the
      benefit of emotional support; however, no evidence was obtained for he proposed
      buffering effect of emotional support.

PMID- 9923172
TI  - Problem-solving in relation to abuse by a partner.
AB  - The present study investigated the usefulness of the construct of abuse-related
      problem-solving in relation to the reported experience of abuse by a partner in
      both clinical and nonclinical samples of women. Data were collected from a
      clinical sample of 101 women who were receiving treatment at a domestic violence
      shelter and from a nonclinical sample of 635 female undergraduates attending a
      medium-sized university. Analysis indicated that women in both samples who
      possessed good abuse-related problem-solving ability reported experiencing less
      abuse from their partners. The usefulness of this construct as well as its
      limitations were noted.

PMID- 9923173
TI  - Structure of the Coolidge Axis II Inventory Personality Disorder Scales from the
      five-factor model perspective.
AB  - Coolidge, et al. in 1994 tested the generality and comprehensiveness of the five
      factor model of personality as applied to personality disorder by performing a
      canonical correlation analysis for the scales from the Coolidge Axis II Inventory
      and the NEO Personality Inventory testing 178 undergraduates (106 men and 72
      women). Their results did not support the generality and comprehensiveness of the
      five-factor model for interpreting the structure of personality disorders. A
      major problem with this study was that the data did not show good simple
      structure and meaningfulness because no rotation was performed for the canonical
      variates. The present study tested the hypothesis that the results of Coolidge,
      et al. might be attributed to the failure to rotate canonical variates to obtain
      good simple structure. For 220 students in introductory psychology (104 men and
      116 women), canonical correlation analysis with varimax rotation was performed
      for scores on the Coolidge Axis II Inventory scales and the NEO Five-Factor
      Inventory scales. The analysis indicated five canonical variate pairs which were
      interpreted as Neuroticism, Extraversion, Openness, Disagreeableness, and
      Conscientiousness, supporting the tested hypothesis as well as the generality and
      comprehensiveness of this model for describing the structure of personality
      disorders.

PMID- 9923174
TI  - AIDS awareness of secondary school pupils in the northern province of South
      Africa.
AB  - This study investigated AIDS awareness in secondary school pupils (mainly
      Northern Sotho and Xitsonga) in the Northern Province of South Africa. The
      randomly chosen sample included 622 Standard 9 pupils (254 boys and 368 girls) in
      the age range of 17 to 24 years (M of 19.3), who were administered a
      questionnaire on awareness of AIDS and socioeconomic status. Over 72% of the
      questions about AIDS were correctly answered, which suggests a fair amount of
      accurate information about AIDS; however, 18% were of the opinion that "AIDS does
      not exist" and 19% that "there is a cure for AIDS." Analysis of variance
      indicated no relationships for sex, age, ethnicity, or socioeconomic status with
      correct answers.

PMID- 9923175
TI  - Engaging in "illusory control" during repeated risk-taking.
AB  - Risk-taking behavior occurs when an individual chooses to engage in a game of
      chance. Although the outcomes of these games are completely random, many
      individuals believe that they can exercise some control over the outcomes. The
      present study examined the extent to which five undergraduate roulette players
      would pay additional money for opportunities to engage in an illusory activity
      that had no influence on the game's outcome, i.e., choosing random numbers rather
      than having the experimenter choose them. All five subjects engaged in this type
      of activity and the extent to which they did was linearly related to the player's
      winnings. These findings may suggest why people continue to gamble when the odds
      of winning are against them.

PMID- 9923176
TI  - Relationship between the Wide Range Achievement Test 3 and the Wechsler
      Individual Achievement Test.
AB  - The present study examined the relationship between the Wide Range Achievement
      Test 3 and the Wechsler Individual Achievement Test for a sample of children with
      learning disabilities in two rural school districts. Data were collected for 87
      school children who had been classified as learning disabled and placed in
      special education resource services. Pearson product-moment correlations between
      scores on the two measures were significant and moderate to high; however, mean
      scores were not significantly different on Reading, Spelling, and Arithmetic
      subtests of the Wide Range Achievement Test 3 compared to those for the basic
      Reading, Spelling, and Mathematics Reasoning subtests of the Wechsler Individual
      Achievement Test. Although there were significant mean differences between scores
      on Reading and Reading Comprehension and on Arithmetic and Numerical Operations,
      magnitudes were small. It appears that the two tests provide similar results when
      screening for reading, spelling, and arithmetic.

PMID- 9923178
TI  - Effect of ease-of-acquisition on naming latency for Japanese kanji: a reanalysis
      of Yamazaki, et al.'s (1997) data.
AB  - Yamazaki, Ellis, Morrison, and Lambon Ralph in 1997 found two age-of-acquisition
      measures exerted greater independent effects on the naming latency of kanji than
      well-established variables such as word frequency. The current study is a sequel
      to that study but has reached a different conclusion. To find a better predictor
      than the two age-of-acquisition measures, Yamazaki, et al.'s data were reanalyzed
      with the new variable, ease-of-acquisition. The main finding was that the
      correlation between ease-of-acquisition at age 13 and naming latency was high .67
      (df = 145, p < .001). The status of ease-of-acquisition and its possible role in
      psycholinguistic research are briefly discussed.

PMID- 9923177
TI  - Sense of coherence as a modifier of occupational stress exposure, stress
      perception, and experienced strain: a study of industrial managers.
AB  - 750 male industrial managers participated in a survey specifying the role of
      sense of coherence in occupational stress. A strong sense of coherence buffered
      from strain almost independently of respondents' age, exposure to stressors, or
      perceived stressors; however, a strong sense of coherence was slightly related to
      the selection of individuals into jobs characterized by relatively low exposure
      to such stressors as lack of control and role ambiguity. Sense of coherence did
      not moderate the relationship among exposure to stressors, perceived stressors,
      and strain experienced.

PMID- 9923179
TI  - Pets and health.
AB  - Beneficial and adverse effects of pets for individuals in a wide range of
      circumstances have been reported. Nevertheless, well-designed unbiased
      experiments and long-term follow-up studies are needed. Pets appear to be
      therapeutic for some individuals and deleterious for others. The controversies
      concerning the effects of pets on health merit objective assessment by unbiased
      researchers.

PMID- 9923180
TI  - Response difficulty: response rate relation and sex of subjects.
AB  - Past research on the relation between response effort and response rate in humans
      has not considered the effect of subjects' sex. Subjects (22 men and 23 women)
      were asked to pull a trigger repeatedly when the force required to pull the
      trigger was varied for each subject at 5, 10, 15, or 20 lb. At the lower force
      requirements, combined, women made more responses than at the combination of the
      two higher force requirements. For men, however, this relation was reversed.
      Possible implications of these findings are discussed.

PMID- 9923181
TI  - MMPI-2 and MMPI-A research with U.S. Latinos: a bibliography.
AB  - This bibliography presents a comprehensive listing of all research conducted on
      U.S. Latinos, including Puerto Ricans, with the MMPI-2 and MMPI-A beginning in
      1989. A total of 52 studies and 6 additional resources are listed. Researchers
      and clinicians could use this bibliography for the culturally appropriate
      application of the MMPI-2/MMPI-A with this growing population.

PMID- 9923182
TI  - Systemic lupus erythematosus and dementia.
AB  - Comparison of Trail-making Parts A and B and the Shipley Conceptual Quotient of
      18 index patients (M age = 29 years) and 18 controls indicated no dementia for
      the index patients.

PMID- 9923183
TI  - Differential prediction of maladjustment scores with the Snyder Hope subscales.
AB  - The present study examined the relation between two Synder Hope subscales
      (Agency: goal motivation; Pathways: goal planning) and adjustment problems (a
      composite of seven MMPI-2 clinical scales). Each of 354 university students
      completed both the Hope Scale and the MMPI-2. Whereas scores on Hope, Agency, and
      Pathways subscales were each negatively related to the maladjustment composite
      score, the relation was significantly stronger for the Agency than for the
      Pathways subscale. For individual clinical scales, the Agency subscale offered
      better prediction than the Pathways subscale for all selected clinical scales
      except Hysteria and Psychopathic Deviate. The Agency subscale also offered better
      prediction than the Hope Scale for Psychaesthenia and Schizophrenia. Applications
      for health professionals and directions for research are discussed.

PMID- 9923184
TI  - Protestant Work Ethic as a moderator of mental and physical well-being.
AB  - This study tested hypotheses about effects of the Protestant Work Ethic on mental
      and physical well-being. The Protestant Work Ethic was expected to enhance mental
      and physical well-being and buffer response to adverse work conditions. Blue
      collar workers (N = 115) filled out questionnaires. As predicted, workers with
      high scores on a Protestant Work Ethic scale are more satisfied with their jobs
      than workers with low scores. General health complaints are partly explained by
      an interaction between Protestant Work Ethic and Job Richness: when jobs lacked
      Job Richness, employees with a high Protestant Work Ethic report fewer General
      Health Complaints than employees with a low Protestant Work Ethic. No interaction
      effect was found of Protestant Work Ethic for the relationship between Physical
      Working Conditions and well-being.

PMID- 9923185
TI  - Death anxiety, coping resources, and comfort with dying patients among nurses in
      AIDS care facilities.
AB  - 437 nursing staff members in seven AIDS residential health care facilities in New
      York City were asked to complete a questionnaire consisting of the Death Anxiety
      Scale, the Coping Resources Inventory, the Comfort with Dying Patients Scale, and
      a Demographic Section. 197 usable questionnaires were returned. There were
      statistically significant racial or ethnic differences in scores on physical
      coping resources, with African-Americans reporting the fewest resources. No
      significant relations were found between scores on death anxiety, coping
      resources, and comfort with dying patients. Multivariate analysis of variance was
      used to assess the interaction of the Nursing group (professional or
      paraprofessional nurses), Death anxiety, and Coping resources with Comfort with
      dying patients. There were no statistically significant differences for death
      anxiety, coping resources, and comfort with dying patients by the Nursing group.

PMID- 9923186
TI  - Characteristics of APA Division 40 Fellows and ABPP Diplomates in clinical
      neuropsychology.
AB  - Diplomate and Fellow status in clinical neuropsychology reflect professional
      competency and a record of significant contributions to the field. This present
      study provides a snapshot of the pathways to these distinctions and focuses on
      the educational history and demographic description of ABPP Diplomates and APA
      Division 40 Fellows. Identification of degree-granting institutions of these
      psychologists provides distal outcome data for training programs. Both
      credentials were identified as midcareer markers, as attainment of either
      required over 12 years of postdoctoral experiences. The pool of Fellows is
      significantly older than the Diplomates, but these data are confounded as 53
      individuals hold both a diploma and Fellow status. Women were underrepresented in
      both groups. In regard to degree specialty, clinical psychology was the most
      prevalent degree program represented; however, the groups appear to be permeable
      to psychologists who received formal training in other subspecialties.

PMID- 9923187
TI  - Disease and depression in older medical patients.
AB  - It was hypothesized that those with systemic diseases such as diabetes mellitus
      would likely have higher prevalence rates of self-reported depressive symptoms
      than those diagnosed with nonsystemic diseases in part due to the disability
      conferred by their diagnosis. Analysis indicated partial support, although, other
      factors may moderate this relationship.

PMID- 9923188
TI  - Abortion affiliation, urban size, and geographic bias of responses to lost
      letters.
AB  - A study using 1800 "lost letters" was designed to test the hypothesis that
      returned responses would be greater in smaller rural communities (population M =
      964) than in a city (population = 60,591) or the suburbs (population = 195,847)
      unless the addressee was affiliated with a pro-abortion group. Returns to
      control, Committee For Free Abortion, and Committee Against Free Abortion
      affiliates were 37.2%, 24.0%, 29.3%, respectively. From the city, the number of
      returned letters was much larger than the number from the suburbs except for
      those letters with an affiliation to the pro-abortion condition. Returned letters
      from the city were fewer than those from smaller rural communities except those
      letters affiliated with the pro-abortion group. More letters affiliated with the
      pro-abortion condition were returned from the suburbs than from the smaller rural
      communities. The geographic condition influenced over-all rates of return. Rates
      were higher when letters were addressed to a city P.O. Box than to a rural one.
      Second, rates were also greater in smaller rural communities for letters bearing
      "in-town" (Molino) and "out-of-town" (Pensacola) addresses than those from the
      city bearing an "out-of-town" (Molino) address. These findings seem to indicate
      the possibility that there may be some geographic bias in the willingness of
      people to help a stranger in need by returning a lost letter.

PMID- 9923190
TI  - Social anxiety and training in neurolinguistic programming.
AB  - The Liebowitz Social Phobia Scale measured the effect of training on social
      anxiety responses of 28 adults prior to and following a 21-day residential
      training, and at 6 mo. follow-up. Significant reductions posttraining and at
      follow-up were evident in the mean self-reported global scale scores on fear and
      avoidance behavior in social situations. The item scores, aggregated to reflect
      the situational domains of formal and informal speaking, being observed by
      others, and assertion, showed significant and continuing reduction from
      posttraining through follow-up. These findings are consistent with the hypothesis
      that this training may be associated with reduced responses to social anxiety,
      but as there was no formal control group, pretest scores from another study were
      used. Interpretation is limited.

PMID- 9923189
TI  - Feedback on ability in counseling, self-efficacy, and persistence on task.
AB  - Self-efficacy in counseling varied with randomly manipulated feedback on ability,
      such that the 29 college students who received negative feedback on their ability
      reported lower self-efficacy than those 16 who received positive feedback.
      Persistence on task, however, was not related to the type of feedback received.

PMID- 9923191
TI  - New NO donors with antithrombotic and vasodilating activities, Part 26.
      Amidoximes and their prodrugs.
AB  - Seventeen amidoximes (2a-q) comprising aliphatic (2a-d), aromatic (2e-n), and bis
      compounds (2o-q) have been synthesized. In the Born test 4
      chlorophenylethenecarboxamidoxime (21) was most active and inhibited the blood
      platelet aggregation induced by collagen with an IC50 = 3 microM. After oral
      administration to rats (60 mg/kg) fourteen compounds significantly inhibited the
      formation of thrombi in arterioles and venules. The strongest effect was observed
      with ethene-bis-carboxamidoxime (2q) (31% in arterioles and 18% in venules). The
      O-ethoxycarbonylderivatives 3 and the corresponding 1,2,4-oxadiazol-5-ones 4,
      which had been synthesized as prodrugs, showed smaller antithrombotic effects.

PMID- 9923192
TI  - Anthracene-1,4,9,10-tetraone derivatives: synthesis and antitumor activity.
AB  - A series of 2-alkylated anthracene-1,4,9,10-tetraone (ATO) derivatives were
      synthesized, and their antitumor action in ICR mice bearing S-180 cells and
      antiproliferative activity against L1210 cells were evaluated. Overall, the
      introduction of an alkyl group (C1-C8) at C-2 enhanced the antiproliferative
      activity. Among 2-(1-hydroxyalkyl)- or 2-(1-acetoxyalkyl)-ATO derivatives, four
      compounds possessing alkyl chain of an intermediate size (C4-C6) gave T/C values
      of > 300%. Acetylation at 1'-OH failed to cause an enhancement in the antitumor
      action, in contrast to a remarkable increase in antiproliferative activity.
      Although there was no direct relationship between antiproliferative activity and
      antitumor action, the compounds with lower antiproliferative activity tended to
      show higher antitumor activity. Further study shows that the antiproliferative
      activity of ATO derivatives may be explained properly neither by redox cycling
      nor arylating capacity.

PMID- 9923193
TI  - Synthesis of 2,5-disubstituted-1,4-benzoquinone derivatives as potential
      antimicrobial and cytotoxic agents.
AB  - A number of 2,5-disubstituted-1,4-benzoquinone derivatives were prepared and
      characterized by elemental analysis, infrared (IR), nuclear magnetic resonance
      (1H-NMR), and mass spectra (MS). These compounds and their synthetic precursors
      were evaluated for their in vitro antimicrobial and cytotoxic activity. The most
      potent antimicrobial compound was the thiadiazolyl derivative 4b, which was 2- to
      4 times more active than the antimicrobial drug sulfathiazole. All the tested
      compounds were active in the Brine Shrimp Lethality (BS) Test. Compound 4e which
      was the most active in the BS test was also found to possess a significant
      cytotoxicity against two tumor cell lines. Some of the compounds were found to be
      mutagenic at relatively high concentration.

PMID- 9923194
TI  - 5-Arylidene-3-aryl-pyrrolidine-2,4-diones with affinity to the N-methyl-D
      aspartate (glycine site) receptor, Part I.
AB  - A series of new 5-arylidene 3-aryl-pyrrolidine-2,4-diones has been prepared.
      Their binding affinity toward the N-methyl-D-aspartate (glycine site) receptor
      has been measured as a basis for more detailed structure-activity relationship
      studies.

PMID- 9923195
TI  - Synthesis of potent non-imidazole histamine H3-receptor antagonists.
AB  - Histamine has been converted into a non-imidazole H3-receptor histamine
      antagonist by addition of a 4-phenylbutyl group at the N alpha-position followed
      by removal of the imidazole ring. The resulting compound, N-ethyl-N-(4
      phenylbutyl)amine, remarkably has a Ki = 1.3 microM as an H3 antagonist. Using
      this as a lead compound, a novel series of homologous O and S isosteric tertiary
      amines was synthesised and structure-activity studies furnished N-(5
      phenoxypentyl)pyrrolidine (Ki = 0.18 +/- 0.10 microM, for [3H]histamine release
      from rat cerebral cortex synaptosomes) which, more importantly, was active in
      vivo. Substitution of NO2 into the para position of the phenoxy group gave N-(5-p
      nitrophenoxypentyl)pyrrolidine, UCL 1972 (Ki = 39 +/- 11 nM), ED50 = 1.1 +/- 0.6
      mg/kg per os in mice on brain tele-methylhistamine levels.

PMID- 9923196
TI  - Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid
      (FAA). Part 3: 2-Heteroaryl derivatives.
AB  - A range of 14 derivatives of flavone-8-acetic acid (FAA) with a heterocyclic
      substituent in place of the 2-phenyl group have been prepared and their anti
      tumour activity evaluated in vitro against a panel of human and murine tumour
      cell lines and in vivo against MAC 15A. Some of the compounds, notably 2c,d and
      s, showed significant in vivo activity and these require further studies in order
      to evaluate their potential for development.

PMID- 9923197
TI  - High altitude maladies: recent trends in medical management.

PMID- 9923198
TI  - Effect of indomethacin on hyperthermia induced by heat stress in broiler
      chickens.
AB  - An investigation was carried out to verify whether the heat stress hyperthermia
      response of broilers is prostaglandin-dependent. Male broiler chickens of the
      Hubbard-Petterson strain, aged 35-49 days, were used. Chickens were injected with
      indomethacin (1 mg/kg intraperitoneally) 15 min before or 2 h after heat exposure
      (at 35 degrees C for 4 h), and rectal temperature was measured before injection
      and up to 4 h thereafter. Birds were separated into two groups with and without
      access to water during heat stress. The increase in rectal temperature was lower
      (P < 0.05) in birds with access to drinking water during heat exposure. All birds
      injected with indomethacin exhibited an increase in rectal temperature,
      irrespective of whether indomethacin was administered before or in the course of
      the rise in temperature. The results revealed that the increase in rectal
      temperature during heat exposure is not prostaglandin-dependent, and that the use
      of cyclooxigenase inhibitors is not recommended to attenuate heat stress
      hyperthermia in broiler chickens.

PMID- 9923199
TI  - Biometeorological classification of daily weather types for the humid tropics.
AB  - This paper describes the methodology for an objective classification of weather
      types for biometeorological purposes in a tropical-humid climate, such as the
      Cuban climate. The classification considers the daily behavior of extreme air
      temperatures, the mean partial vapor pressure, the mean diurnal cloudiness, the
      wind speed at 1300 hours local time, and the occurrence of precipitation during
      the day, in order to identify up to 18 weather types. Descriptions are given of
      the main biometeorological characteristics of some significant weather types,
      considering typical geographical locations, and their seasonal variations related
      to the seasonal pattern of asthma and acute respiratory infections. The
      relationship between the daily occurrence of diseases and the distribution of
      these local weather types is also described. A significant relationship was found
      between the incidence of cardiovascular and neurological diseases and the
      occurrence of hot stress, while the presence of cold and very cold days was
      closely related with increases of bronchial asthma in adults and children. The
      appearance of large meteoropathological reactions in the native population could
      be explained by the day to day pattern of change in the weather types.

PMID- 9923200
TI  - Changes in the seasonality of mortality in Germany from 1946 to 1995: the role of
      temperature.
AB  - Based on records from the Federal Bureau for Statistics of Germany, the
      seasonality of mortality was investigated for the period 1946-1995. Lowest
      mortality rates were found during summer (August or September) while highest
      values were found in winter (January through March). Non-linear regression of all
      monthly mortality data with the average monthly temperatures in Germany revealed
      a significant negative relationship (r = -0.739; n = 600; P < 0.0001). The fact
      that the differences between the long-range monthly temperatures and the
      individual monthly temperatures also showed a distinct relationship to the
      mortality rates speaks against a mere coincidence of both parameters. The
      amplitude of this seasonal rhythm declined steadily within the observation
      period. It is concluded that low temperatures cause an increase in mortality
      rates and that this effect has become less important during recent decades due to
      the increased use of central heating and because of improvements in the public
      health system.

PMID- 9923201
TI  - Marriage season, promptness of successful pregnancy and first-born sex ratio in a
      historical natural fertility population--evidence for sex-dependent early
      pregnancy loss?
AB  - We investigated population-based vital records of the seventeenth and eighteenth
      century French Canadian population to assess the effects of marriage season on
      the outcome of the first births under natural fertility conditions (n = 21,698
      marriages). Promptness of the first successful conception after marriage differed
      according to marriage season; the proportion of marriages with a marriage-first
      birth interval of 8.0-10.0 months was lowest (34%) for marriages in August
      October (P = 0.001). Although the male/female sex ratio of the babies born with
      an interval of 8.0-10.0 months was generally higher (1.10) than those with an
      interval of 10.0-24.0 months (1.05), the marriages in August-October resulted in
      a significantly reduced sex ratio (0.96) among only the prompt conceptions (P =
      0.026). We discuss whether this seasonal reduction of the sex ratio could be
      partly explained by a clustered pregnancy loss of male zygotes in early
      pregnancy.

PMID- 9923202
TI  - New units for indoor air quality: decicarbdiox and decitvoc.
AB  - Two new units are proposed for the evaluation of indoor air quality using the
      decibel concept, which give a much better approximation of the human perception
      of odour intensity, compared to the CO2 and total volatile organic compounds
      (TVOC) concentration scales: the decicarbdiox and the devitvoc. On the
      psychophysical scale according to Yaglou, the weakest odour that can be detected
      by the human smell sensors is equal to one, and corresponds to the lower limit of
      percentage dissatisfaction (PD) of 5.8%. It is equivalent to: (1) a CO2 threshold
      concentration of 485 ppm-0 dB (odour CO2)-0 dCd (decicarbdiox), and (2) a TVOC
      threshold concentration of 50 micrograms m-3-0 dB (odour TVOC)-0 dTv (decitvoc).
      The upper limit is determined by the initial value of toxicity: (1) CO2-15,000
      ppm-134 dCd, and (2) TVOC-25,000 g/m-3-135 dTv. Optimal pollutant values
      (corresponding to PD = 20%) and admissible values (PD = 30%) for unadapted and
      adapted persons are calculated. Long-term tolerable values (determining the sick
      building syndrome range) and short-term tolerable values (the beginning of the
      toxic range) are also stated. The same system used to evaluate noise can be used
      to evaluate air quality. Additionally, the contribution of the individual
      constituents (at present acoustic and odour) to the overall quality of the
      environment can be ascertained. The new units dCd and dTv can express an increase
      or decrease in air contamination, e.g. by the use of air cleaners, new building
      materials etc. The proposed system of using dCd and dTv is compatible with
      BSR/ASHRAE 62-1989 R which can be used to determine the required volume of fresh
      air for ventilation by an improved method, which takes into account different
      levels of required indoor air quality.

PMID- 9923203
TI  - Breast cancer and fatigue: issues for the workplace.
AB  - 1. Women with breast cancer are at high risk for fatigue as a side effect of
      treatment with surgery, radiation, and chemotherapy. The risk is compounded by
      the multiple roles of women who return to work during treatment. 2. The fatigue
      experience includes a physical component of decreased functional status, an
      affective component of emotional distress, and a cognitive component of
      difficulty concentrating. These characteristics of fatigue may present
      significant challenges for employees. 3. The Family Medical Leave Act provides 12
      weeks of unpaid leave to receive medical treatment and/or recover from treatment
      for breast cancer. 4. The nurse in the workplace can assess and monitor the
      effects of fatigue and teach employees to manage fatigue through energy
      conservation, effective use of energy, and health promotion activities to restore
      energy levels.

PMID- 9923204
TI  - Prostate cancer: clinical perspectives.
AB  - 1. When obtaining a screening history for prostate cancer, important risk factors
      include age, family history, and ethnicity. The digital rectal examination
      remains the "gold standard" physical examination screening technique. 2. If
      prostate cancer is detected at an early stage, it is potentially curable. It is
      incumbent upon occupational health care providers to afford those constituents
      who fall into a high risk category, or who are > or = 40 years of age, every
      opportunity for prostate cancer screening. 3. Education is the "sine-qua-non" of
      complete health care provision for prostate cancer clients. The occupational
      health care provider can play a pivotal role in allaying a client's fear and
      misconception of this disease. 4. Providing appropriate assessment and advocacy
      for clients returning to the workplace following diagnosis and treatment of
      prostate cancer is crucial.

PMID- 9923205
TI  - Worksite breast cancer screening programs: a review.
AB  - 1. Breast cancer is a major health problem amenable to secondary prevention for
      reducing morbidity and mortality. 2. Given the large and increasing numbers of
      women in the workplace, breast cancer prevention and control measures should be
      included in workplace health promotion programs. However, despite the increasing
      prevalence of worksite health promotion programs in the United States, the
      prevalence of breast cancer programs in the workplace has been decreasing. 3.
      Despite the limited evaluative research of worksite breast cancer screening
      programs, a number of important conclusions conducted thus far. 4. Additional
      scientifically rigorous evaluation studies of worksite health programs for the
      early detection of breast cancer are needed, and additional innovative workplace
      programs aimed at increasing breast cancer screening need to be developed.

PMID- 9923206
TI  - Alternative and complementary therapies: integration into cancer care.
AB  - 1. Cancer survivors and caregivers in the workplace are using complementary and
      alternative therapies and expect nurses to know about them. 2. Therapies such as
      acupuncture, acupressure, homeopathy, herbal preparations, imagery, and
      Therapeutic Touch among others may help with cancer symptoms or treatment
      effects. 3. Specific strategies, e.g., staff stress management programs,
      inservice or continuing education, inclusion of therapies on assessment forms,
      can be used to begin integrative efforts. 4. The ideal health care system is one
      that integrates alternative and complementary healing therapies into conventional
      care.

PMID- 9923207
TI  - Agricultural workers.

PMID- 9923208
TI  - The Interhospital Interpreter Project.
AB  - My family immigrated to Canada when I was a child. Soon after we arrived, I
      became ill with acute appendicitis. For days, I lay in pain while my parents
      searched desperately for a physician. But in the small Ontario town where we had
      moved, there were no cultural interpreters. My parents faced not just a language
      barrier, but the barrier of a lack of knowledge of the health care system. They
      were unaware that an ill person could seek treatment in the emergency department
      of a general hospital. My parents finally found someone who could help, and I was
      treated just hours before my appendix would have ruptured. I will never forget
      those days of pain and fear.

PMID- 9923209
TI  - Making sense of research.
AB  - Nurses throughout the country are striving to continually provide the highest
      quality of care to clients, despite the shrinking health care budgets of today.
      We are being forced to do more with less, while trying to ensure that our care is
      both effective and efficient. An important step toward ensuring that the benefits
      of our practice match or exceed the cost of providing them is research-based
      practice.

PMID- 9923211
TI  - [The interpreter in an intercultural clinical milieu].
AB  - The public's diversified language profile means that nursing practice must adjust
      to provide the same quality of care to all clients, no matter what language they
      speak. To improve quality and quantity of information exchanged in the nurse
      client-interpreter triangle, the authors have investigated the type of
      information likely to be filtered and studied the various factors underlying the
      interpreter's choice to filter information. The authors also analyzed the values
      interpreters assign to information and the factors that form the background for
      filtering, including mistrust. The authors suggest adequately preparing
      interpreters; using interpreters' expertise; and developing an appropriate
      training program for intercultural interpreters to enable them to better function
      within health care institutions.

PMID- 9923210
TI  - Skin wounds. Assessment and care.
AB  - The primary goal of any skin care program should be prevention of breakdown.
      Unfortunately, that goal is not always achievable. As our bodies age or when they
      become immunosuppressed, incontinent, malnourished, underhydrated, immobile or
      simply fragile, our skin is less able to preserve its integrity or heal on its
      own.

PMID- 9923213
TI  - Using the Internet to support self-care.
AB  - Nurses have long recognized the importance of self-care. In the current
      Information Age, nurses can use the Internet to locate computer- and non-computer
      based programs and tools that encourage people to become active consumers who
      control decisions and actions related to their health. The Internet can support
      self-care in two main ways: by supplying information and by providing a medium
      for interactive social support. But there are pros and cons to such use of the
      Internet.

PMID- 9923212
TI  - Why do we need peer review?
AB  - Some nurses see peer review as a threatening experience and put up defense
      mechanisms to resist change. Others are recognizing it as a popular performance
      appraisal strategy that will enhance their autonomy and accountability within
      their professional practice. But why do we need it? And what are the benefits?

PMID- 9923214
TI  - New Brunswick's activist archivist. Interview by Barbara Sibbald.

PMID- 9923216
TI  - Managing within a culturally diverse environment.
AB  - Canada has long been a multicultural nation, but the increasing ethnic diversity
      of new Canadians has shifted our multicultural make-up. In 1967, the top five
      countries from which immigrants came to Canada were Britain, Italy, United
      States, Germany and Greece. Almost 30 years later, in 1995, the top five sources
      were Hong Kong, India, the Philippines, China and Sri Lanka.

PMID- 9923217
TI  - Link for kids. The Telehealth Project.
AB  - Telehealth is the use of communications and information technology to deliver
      health and health care services and information over large and small distances.
      Through telehealth, health-related services become more accessible to health care
      providers and consumers in rural, remote and underserviced areas.

PMID- 9923215
TI  - Palliative care. An integral part of life's end.
AB  - While the needs of dying individuals and their families have come under
      increasing scrutiny in the past decade, issues related to the needs of older
      adults (75 years or more) who are dying have not been systematically addressed.
      Death and dying are increasingly associated with old age, yet the
      conceptualization of palliative care in later life is not well developed. All too
      often, the philosophy and principles of palliative care are not invoked in the
      care of people who are both old and dying. It is an omission that must cease.

PMID- 9923218
TI  - Educating parish nurses.
AB  - During the early 1980s, as government health care reimbursement systems changed
      in the United States, an interest developed in strengthening healing alliances
      between health care facilities and faith communities. At the same time, Reverend
      Granger Westberg recognized the untapped resources of professional nurses that
      could be made available to parishioners. This recognition led to Westberg's
      pioneering of parish nursing as a way for faith communities to reclaim their
      healing mission. The value of reconnecting nurses to their traditional roots in
      faith communities spread quickly across the United States, and there are now over
      3,000 registered nurses practising within American faith communities.

PMID- 9923219
TI  - [Palliative care, a humanitarian way (Part 1)].
AB  - Fully experiencing the last moments of life, in a setting of relative calm and
      affection, is one of the victories won by the Western movement to rediscover
      death, which began three decades ago. The author describes the fertile ground
      from which this movement emerged and makes no pretence of defending medical
      technology that today supports a multitude of tests in a sort of diagnostic
      obsessiveness before shifting to a therapeutic obsession in treating people with
      incurable disease. The author instead advocates the benefits of death with
      dignity. A well structured analysis of the palliative approach confirms the
      inalienable nature of human freedom and dignity.

PMID- 9923221
TI  - Telephone advice: is it safe?
AB  - Telephone advice in health care is always risky. Until the last few years
      practitioners--with a few exceptions such as poison control personnel--were
      generally warned not to give telephone advice to anyone. The possibility of harm
      resulting, and of a lawsuit against the health care provider, was just too great
      a risk.

PMID- 9923220
TI  - Turning body time to shift time.
AB  - Studies have shown that shift work can have a negative impact on job performance,
      sleep, physical and emotional health, social life, family life, drug use and
      level of job-related stress. For nurses, these negative effects have consequences
      not just for the individual, but for the workplace, as decreased alertness and
      reduced job performance could endanger human lives.

PMID- 9923222
TI  - Dispelling the myths of CPR.
AB  - Without a "do not attempt resuscitation" order on a patient's chart, nurses are
      obliged to initiate cardiopulmonary resuscitation (CPR) on all patients who die
      in hospital. Their discomfort with this situation is often related to the
      perception that resuscitation attempts are being carried out, at best,
      inappropriately and, at worst, unethically.

PMID- 9923223
TI  - "The possibilities are great". Interview by Barbara Sibbald.

PMID- 9923224
TI  - An eating disorders prevention program.
AB  - PROBLEM: To develop, implement, and evaluate a school personnel training program
      on eating disorders. METHODS: The pretest-posttest control group design was used
      to examine effects of this training with 117 high school personnel. Both
      experimental (n = 85) and control (n = 32) groups were given a pretest and a
      posttest on knowledge and attitudes. The experimental group participated in a
      training program. Both groups were asked to keep a 3-month count of students at
      risk for eating disorders. FINDINGS: Results included a significant difference in
      knowledge between the experimental and control groups. School personnel in the
      experimental group were more likely to identify students at risk for developing
      eating disorders. CONCLUSIONS: Training school personnel to identify students at
      risk for eating disorders holds promise as a strategy for dealing with this
      disease. All at-risk students for eating disorders should be further evaluated
      and additional treatment initiated as needed.

PMID- 9923225
TI  - Psychiatric interviews with pediatric gunshot patients.
AB  - PROBLEM: To understand the life experiences of gunshot-injured children to obtain
      information about predisposing factors to injury. METHODS: A pilot study of 16
      hospitalized children (14 males, 2 females) between the ages of 11 and 15 who
      sustained gunshot injuries. Each child was psychiatrically assessed on a medical
      inpatient unit after sustaining a gunshot injury to assess the rate of acute
      stress disorder and other comorbid psychiatric diagnoses. FINDINGS: Findings
      showed gunshot-injured children had a 56% rate of acute stress disorder, and 68%
      had a past psychiatric history. CONCLUSIONS: Gunshot-injured children require
      psychiatric intervention to minimize the long-term effects of acute stress
      disorder. Further research is needed to clarify the relationship of gunshot
      injury and dysfunctional behavior and develop effective treatment options.

PMID- 9923226
TI  - Childhood anger: so common, yet so misunderstood.
AB  - PURPOSE: To review findings of recent research studies on anger in children and
      adolescents, the outcomes of mishandled anger and interventions to promote
      appropriate anger management. SOURCE: Published literature. CONCLUSIONS: Anger
      may be a healthy or unhealthy response in children experiencing small
      frustrations or great injustices. Research findings vary and there is a need to
      clearly define anger and the correlates of anger in children and adolescents. In
      addition, there are limited studies on anger management strategies and their
      effectiveness that would assist healthcare professionals.

PMID- 9923227
TI  - The potential value of small responses and partial solutions.

PMID- 9923228
TI  - Erroneous beliefs about research held by staff nurses.
AB  - BACKGROUND: Experiences in working with nurses conducting research in clinical
      settings have uncovered a number of beliefs that may create unnecessary obstacles
      and limit research efforts. This article discusses these beliefs and provides
      examples. METHOD: Although this article was not conceptualized as a research
      study, the information was gleaned through working with nurses on a day-to-day
      basis as a researcher. RESULTS: Eleven beliefs were identified and discussed.
      CONCLUSION: These beliefs have implications for nurses who are attempting to
      conduct clinical research. The intent of the article is to educate nurses
      regarding the philosophy of science and research methods in this context.

PMID- 9923229
TI  - Accreditation of continuing education: the critical elements.
AB  - Accreditation in nursing continuing education (CNE) is central to professional
      values such as accountability, competence, and knowledgeable practice.
      Organizations choosing to participate in the accreditation/approval system make a
      commitment to quality. This article reviews the history of accreditation, defines
      the language, describes the system and process, and discusses agency/institution
      characteristics that should be in place before beginning an accreditation
      application process. The American Nurses Credentialing Center Commission on
      Accreditation model is used as the prototype.

PMID- 9923230
TI  - A review of preceptorship in undergraduate nursing education: implications for
      staff development.
AB  - Nurse educators regularly develop clinical learning experiences for undergraduate
      students using the expertise of experienced RNs as preceptors. Preceptors help
      students develop a knowledge base and clinical skills. This article reports a
      literature review and summarizes the benefits of preceptorship, outlines
      preceptor responsibilities and qualities, and discusses the process of preceptor
      selection and role preparation. Suggestions for collaborative efforts regarding
      the preceptor experience among staff nurses, nurse educators, and staff
      development educators are highlighted.

PMID- 9923231
TI  - Teaching basic dysrhythmias: what is the best approach?
AB  - Nurses' ability to accurately interpret cardiac dysrhythmias has resulted in
      decreased mortality. Four educational approaches to teaching dysrhythmia
      interpretation were evaluated. Major findings revealed learning was more
      effective when the lecture-discussion approach was used over a 5-week to 10-week
      period of time. Nurses also felt more comfortable with their ability to interpret
      dysrhythmias. These findings have several implications for continuing education
      departments regarding how and over what period of time this content should be
      taught.

PMID- 9923232
TI  - The use of gaming strategies in a transcultural setting.
AB  - Saudi Arabia's vast economic resources have enabled the development of state-of
      the-art hospitals. Nurses recruited from around the world staff these hospitals
      creating one of the most multicultural practice settings in the world. Ethnic,
      educational, and experiential diversity; language and communication barriers; and
      alternative ways of knowing and learning challenge nurse educators to be more
      creative and explore opportunities for greater participation and learning among
      various cultural groups. Gaming, as a teaching-learning strategy for
      multicultural participants, affords the necessary flexibility and nonthreatening
      atmosphere which facilitates positive interactions among different, and often
      competing, communication patterns and learning styles. This article explores how
      and why gaming is as an effective educational strategy in a transcultural
      setting.

PMID- 9923233
TI  - Delaware RNs' reasons for nonparticipation in continuing education.
AB  - A descriptive study determined the reasons for nonparticipation in continuing
      education (CE) for RNs living in Delaware, where lack of CE results in loss of
      licensure. Subjects were asked to complete a 40-item Deterrents to Participation
      Scale with a 13-item demographic questionnaire. The sample (N = 94) identified
      disengagement as the primary factor for predicting nonparticipation in CE, with
      the primary reason being they had higher priorities than CE in their lives.
      Implications for nursing administrators and educators are discussed.

PMID- 9923234
TI  - Creative teams: an experiential activity.
AB  - BACKGROUND: Staff development educators in a Department of Education &
      Development were seeking a creative activity to reinforce the qualities of
      effective teams. METHOD: Staff development educators developed an experiential
      activity that provides an opportunity to observe team behaviors by introducing
      several glitches into a goal-oriented team project. Later, observed team
      behaviors were explored with the group. RESULTS: The activity allowed
      participants to practice collaboration, communication, and problem-solving skills
      while functioning as a team. CONCLUSION: This activity, which is easily adaptable
      to any audience, creatively integrates the principles of adult learning to
      provide participants with an opportunity to discuss and practice behaviors
      necessary for teamwork in the current health care settings.

PMID- 9923235
TI  - Older adults as consumers of health care.

PMID- 9923236
TI  - Identification of alcohol-related problems in older women.
AB  - The stereotype of an alcohol or drug abuser rarely elicits an image of an older
      woman. However, if an expanded definition of alcohol abuse is considered, many
      older women are at risk because of normal changes in the body due to aging and
      the high number of prescription and over-the-counter medications they use. This
      article reviews current knowledge about alcohol-related problems in older women.

PMID- 9923237
TI  - Benefits to volunteers in a community-based health promotion and chronic illness
      self-management program for the elderly.
AB  - 1. Volunteers for health promotion programs tend to be younger and healthier than
      program participants. 2. Volunteers in a health promotion program reported
      improved health and function. 3. Nurses involved in health promotion programs can
      extend their efforts by using trained volunteers.

PMID- 9923238
TI  - Senior centers. Shifting student paradigms.
AB  - The purpose of this study was to evaluate an innovative service learning
      experience for new nursing students involving senior citizen centers. Junior
      nursing students (n = 128) were assigned in cohorts to one of five centers for a
      5-week rotation. A questionnaire was administered post hoc to the students,
      teaching assistants, center directors, and a sample of senior citizens at each
      site. The majority of students believed the experience was a valuable part of the
      curriculum and saw prospects for community health nursing roles. However, they
      had concerns regarding losing time in acute care and relevance and number of
      assignments, and reported some difficulty in applying classroom content in the
      setting. Directors and senior citizens were universally positive about the
      experience. Student and teaching assistant reports were key in revising the
      curriculum. Revisions include logistics of the placement of the experience and
      assignments as well as incorporation of this experience within the community
      context.

PMID- 9923239
TI  - A pilot study on improving oral care in long-term care settings. Part I: Oral
      health assessment.
AB  - Surveys of oral health in long-term care (LTC) settings have consistently
      documented low levels of health. In the complex LTC environment, programs to
      improve oral health have yet to be well defined. The purpose of this pilot
      project was to determine if a program of training for nursing assistants in
      combination with adjunctive aids to oral care could improve resident oral health
      indicators. This pilot study demonstrated improved oral health indexes among
      residents cared for by trained nursing assistants who had access to adjunctive
      oral care aids. Additional studies are needed to define the nature of oral
      caregiving in LTC settings as well as specific regimens which can assure
      continued oral health improvement in this environment.

PMID- 9923240
TI  - A pilot study on improving oral care in long-term care settings. Part II:
      Procedures and outcomes.
AB  - This pilot study attempts to determine if a program of training for nursing
      assistants in combination with adjunctive aids to oral care could improve
      resident oral health indicators. Twelve residents of a county long-term care
      (LTC) facility cared for by a group of nursing assistants who completed a 6-week
      oral health training program constituted the experimental group. Resident Plaque
      Index (PI) and Gingival Index (GI) scores were compared at baseline, and 6 weeks
      and 12 weeks after nursing assistant training to a matched group of residents (n
      = 11) cared for by nursing assistants who had not completed oral health training.
      Both the PI and GI scores of the experimental residents improved significantly
      compared to the control residents between baseline and 12 weeks (Student t test,
      p = .039, p = .017, respectively). This pilot study demonstrated improved oral
      health indexes among residents cared for by trained nursing assistants who had
      access to adjunctive oral care aids. Additional studies are needed to define the
      nature of oral caregiving in LTC settings as well as specific regimens which can
      assure continued oral health improvement in this environment.

PMID- 9923241
TI  - Are older women offered adequate health care?
AB  - The "graying of America" will have profound effects on the health care delivery
      system. With shrinking amounts of health care dollars, nurses and primary care
      providers need to promote health maintenance and disease prevention strategies
      that will foster healthier aging. This study was designed to examine the health
      promotion strategies of family practice physicians and residents. The target
      population was a sample of 201 women age 60 and older. The health maintenance
      issues were counseling about hormone replacement therapy (HRT), urinary
      incontinence (UI), and immunizations. The results clearly demonstrated that older
      women were not adequately immunized or counseled about HRT or UI. Nurses can play
      a pivotal role in changing these practices. Nurses can serve as advocates for
      older woman by encouraging them to request these services, or advanced practice
      nurses can provide these services.

PMID- 9923242
TI  - How do you carry out the Healthy People 2000 and the United States Preventive
      Services Task Force recommendations on immunizations, use of hormone replacement
      therapy, and prevention of incontinence in your older clients? Identify client
      information handouts you provide.

PMID- 9923243
TI  - Advance directives: barriers to completion.
AB  - The concept of advance directives, although sound in theory, appears to be
      failing to meet the needs of many patients. Advance directives have been endorsed
      by both the healthcare profession and the general public, yet few individuals
      have documented their wishes for treatment preferences in end-of-life decisions.
      A review of 15 research articles revealed three main barriers to the completion
      and effective use of advance directives. These barriers are: (a) lack of
      education or knowledge regarding advance directives, (b) difficulties with
      paperwork completion, and (c) discordance between patient, family members or
      proxy, and provider. Future research is suggested to generate information that
      will facilitate meeting the needs of patients and their families in this most
      difficult aspect of healthcare delivery.

PMID- 9923244
TI  - Nursing research conferences: benefit or burden.
AB  - The benefits for presenters and participants of three annual nursing research
      conferences were investigated. Results from 133 on-site program evaluations were
      compared to results of surveys developed to capture presenter and participant
      perspectives, 6-22 months post conference. Data from surveys revealed that
      descriptive exploratory studies (the majority of presentations) were evaluated as
      least useful. One third of participants reported that they attempted to apply
      research findings or clinical innovations to their area of practice. A unique
      finding of this study was that presenters experience post-conference benefits,
      such as publishing, consulting, presenting, and project expansion. The results of
      the post conference evaluations differed from the surveys some months after the
      conferences. Planners of continuing education programs are cautioned against
      future conference development based solely on the initial "glow" of on-site
      program evaluations. Study findings clearly suggest that the benefits of nursing
      research conferences to both participants and presenters far outweigh the
      burdens.

PMID- 9923246
TI  - Bibliography: music therapy.

PMID- 9923245
TI  - Music for untying restrained patients.
AB  - The purpose of this descriptive pilot study was two-fold: (a) to test
      psychometrically an observational instrument designed to measure patient
      behaviors displayed while unrestrained and receiving a musical intervention; and
      (b) to determine the effect of a musical intervention on the behavioral reactions
      of physically restrained patients. The Restraint-Music Response Instrument (RMRI)
      is a 40-item observational checklist consisting of 22 positive and 18 negative
      responses developed by the researchers. Content validity was assessed by a panel
      of experts. The RMRI was tested for interrater reliability using three simulated
      and 10 actual patients. Results suggest that the RMRI is a valid and reliable
      measure of patients' responses to music but requires additional study with a
      control group not receiving the intervention.

PMID- 9923247
TI  - An inefficient mix: a comparative analysis of nurse and physician anesthesia
      providers across New York State.
AB  - This study describes the rural and urban distribution of anesthesia providers
      across New York state and contrasts these findings with national distributions.
      It also documents the existence of an inefficient anesthesia provider mix that
      favors physicians over nurse anesthetists and has a major impact on the cost of
      anesthesia delivery in New York.

PMID- 9923248
TI  - Pain management at the end of life: a critical care perspective.
AB  - The nationwide public push for sweeping changes in the care of the dying has
      highlighted dissatisfaction with the way end-of-life care is provided in critical
      care units. This paper addresses barriers to improving that care, and suggests
      assessments and strategies that nurses could use to improve quality in this
      important area.

PMID- 9923249
TI  - The relationship of mentoring to job satisfaction of critical care nurses.
AB  - Mentoring offers a potential buoy in the sea of change in healthcare. Mentoring
      as a relationship between a novice and an expert can help promote stability in
      nursing. Studies have revealed that mentorship enhances the professional growth
      of nursing leaders and educators, but little is found in literature describing
      mentors for nurses engaged in clinical practice. Seventy-six members of a
      critical care nursing specialty organization's clinical practice network,
      spanning regions across the United States, were surveyed by mail. The
      relationship between mentoring and job satisfaction, as measured by the Index of
      Work Satisfaction, was examined. Scores were higher in the mentored group as
      compared to the group without a mentor, but the relationship was not
      statistically significant. Subjects did identify positive characteristics of a
      mentor.

PMID- 9923250
TI  - Baccalaureate nurse educators' workload and productivity: ascription of values
      and the challenges of evaluation.
AB  - An examination of the productivity of baccalaureate nurse educators relative to
      the importance they ascribe to teaching, scholarship, service and professional
      practice may provide insight into the direction of higher education for nursing.
      This review considers the interdisciplinary debate over how workload is
      distributed and how productivity is evaluated. The complexities of objectifying
      what professors do and how well they do it will be presented. It is suggested
      that we consider alternative approaches to determine workload and evaluate the
      productivity of nurse educators. This analysis affirms our disciplinary strengths
      and may have implications for other professional practice disciplines.

PMID- 9923251
TI  - Bibliography: pain management.

PMID- 9923252
TI  - Establishment of wound ostomy continence clinics.

PMID- 9923253
TI  - Collaboration at the millennium: "we must all hang together, or assuredly we
      shall all hang separately".

PMID- 9923254
TI  - NYPD Blue got it right--the power of the mass media in promoting an understanding
      of incontinence as more than just a hygienic problem.

PMID- 9923255
TI  - A reminder.

PMID- 9923256
TI  - Marketing innovations to nurses, Part 2: Marketing's role in the adoption of
      innovations.
AB  - This article is the second in a two-part series concerning marketing techniques
      to enhance nurses' adoption of innovations. Introducing and getting staff to
      implement new policies and procedures constitute an important part of the WOC
      nurse's role. The application of Rogers' Diffusion of innovation Theory provides
      WOC nurses with a framework to introduce innovations into the clinical setting
      and to change subsequent practice patterns. This article introduces the WOC nurse
      to marketing principles needed to successfully introduce a practice innovation to
      nurse colleagues; it also builds upon Rogers' Diffusion of Innovation Theory and
      presents a sample marketing plan as a template for marketing innovations in the
      clinical setting.

PMID- 9923258
TI  - Impact of a decision tree on chronic wound care.
AB  - OBJECTIVE: To examine the use of a decision tree and its impact on the accuracy
      of decision making for chronic wound care. DESIGN: Descriptive comparative
      design; replication study. SETTINGS AND SUBJECTS: Data were collected from 2
      groups of home care nurses in large urban centers. One group was measured after
      initial contact with the decision tree, and the other group was measured 2 years
      after implementation of the decision tree. INSTRUMENTS: The chronic wound
      management decision tree (CWMDT) designed by Knight was used, in combination with
      pictorial case studies developed by Willey and Swords. METHODS: Edmonton Home
      Care Program nurses, having used a decision tree for 2 years, completed 3
      pictorial case studies without the aid of a written copy of the CWMDT. Current
      accuracy of wound care staging and treatment was compared with the Melchior
      MacDougall and Lander results. After this procedure, Calgary Health Services home
      care nurses completed 3 pictorial case studies to assess the accuracy of wound
      care staging and treatment between 2 groups: with the CWMDT and without the
      CWMDT. A questionnaire was completed on factors identified to influence decision
      making in wound care. MAIN OUTCOME MEASURE: Accuracy and confidence of decision
      making in wound care staging and treatment. RESULTS: Accuracy of decision making
      with use of the CWMDT improved over time, as did accuracy of decision making
      after initial contact with the decision tree. Age, experience in nursing and home
      care, number of in-services attended, and number of chronic wounds treated, were
      not found to correlate with accuracy of decision making. CONCLUSION: A decision
      tree can assist with decision making by guiding the nurse through assessment and
      treatment options.

PMID- 9923257
TI  - A quantitative analysis of pressure and shear in the effectiveness of support
      surfaces.
AB  - PURPOSE: We compared pressure and shear among 3 support surfaces in a controlled
      laboratory setting. METHODS: In this comparative study, interface pressure and
      shear were measured in 11 healthy subjects with use of 3 different Medicare
      approved, group 2 therapeutic support surfaces. Each surface was placed on 1 of 3
      identical platforms, allowing for a fixed, 45-degree head-of-bed (HOB) elevation.
      Multiple pressure readings were taken at each test site and each HOB position
      until a measurement that was determined to be reliable was obtained. A shear
      force measurement was obtained using a noninvasive instrument of proprietary
      design, and a formula linking the effects of shear force and pressure was
      calculated. Data were then compared using analysis of variance; specific
      differences were identified using the post hoc Duncan test. FINDINGS: Pressure
      readings on the nonpowered fluid overlay device were lower at the trochanter than
      when compared with the powered, air-filled overlay (23.7 mm Hg vs 36.7 mm Hg; P =
      .017). Both the nonpowered fluid overlay and the powered air-filled mattress
      provided pressure readings at the sacrum with HOB elevation that were lower than
      those recorded on the powered air-filled overlay (16.2 mm Hg and 19.6 mm Hg vs
      27.5 mm Hg, respectively; P < .001). Pressure measurements taken at the heels,
      supine sacrum, and scapula were not significantly different for any of the
      surfaces. Shear force readings were significantly lower on the nonpowered fluid
      overlay when compared with the powered air-filled overlay and powered air-filled
      mattress (79.3 g vs 257.82 g and 231.38 g, respectively; P = .015). CONCLUSIONS:
      Measurements of shear obtained on the nonpowered fluid overlay support surface
      were significantly lower than those obtained on either of the powered support
      surfaces. Reduction in shear force might explain the accelerated healing observed
      in patients being treated with the nonpowered support surface. Randomized
      clinical trials to validate perceptions of enhanced healing rates are required.

PMID- 9923259
TI  - Pathophysiology and management of venous ulcers.
AB  - Venous ulcers account for the majority of chronic lower extremity wounds. The
      cause of venous ulceration is not completely understood; however, risk factors,
      such as a history of deep venous thrombosis (DVT) and a family history of venous
      ulceration, have been identified. Venous ulceration is postulated to occur when
      fibrin cuffs form, leading to increased diffusion distance and impaired local
      perfusion. This article will review the cause, pathophysiology, clinical
      manifestations, and management of venous ulcers.

PMID- 9923260
TI  - Inhibition of moisture penetration to the skin by a novel incontinence barrier
      product.
AB  - OBJECTIVE: To measure the ability of a multiple-barrier product to inhibit the
      passage of a highly water-soluble tracer into the skin when compared with
      products currently available on the market (Peri-Care; Sween Corp., and Double
      Guard; C. R. Bard, Inc.) DESIGN: Dye extraction from the skin was measured at
      specified intervals and a spectrophotometric measurement of the amount of dye was
      obtained. SETTING AND SUBJECTS: Two groups of light-skinned volunteers, 6 young
      adults subjects, aged 22 to 31 years, and 6 older subjects, aged 61 to 73 years,
      were studied in a controlled laboratory setting. INSTRUMENTS: Spectronic 601
      spectrophotometer. METHODS: Rectangles (1 inch x 4 inch), inscribed on the
      ventral forearm skin, were divided into 4 1 inch x 1-inch squares, onto which 50
      microL of different barrier products were spread. Band-Aids (Johnson & Johnson),
      saturated with 70 microL of an FD&C red dye No. 40 solution, were placed over the
      treated squares and left in place for specified intervals up to 8 hours.
      Similarly treated Band-Aids placed onto untreated skin comprised the controls.
      MAIN OUTCOME MEASURE: Amount of dye extracted from the skin as reflected by
      absorbance spectrophotometry. RESULTS: This multiple-barrier product inhibited
      the passage of the tracer into the skin significantly better than the other 2
      products at all time points, except for 1 point in the elderly group. CONCLUSION:
      Noninvasive preclinical methods show that this prototype barrier cream inhibits
      the absorption onto the skin of a solution simulating the density and ionic
      strength of urine. The advantages and limitations of the methods are clarified
      and directions for clinical research are suggested.

PMID- 9923261
TI  - Patient with a recessed, stenosed stoma located in an irregular, pendulous
      abdomen and the presence of pseudoverrucous lesions.

PMID- 9923282
TI  - Hemolytic crisis: the Dialysis Center of Lincoln experience.

PMID- 9923284
TI  - Unleashed fury. Proposed changes to transplant allocation policy sets off storm
      of reaction

PMID- 9923285
TI  - The ups and downs of a kidney transplant.
AB  - While a kidney transplant is not touted by the renal community as a cure, 38,000
      people are currently waiting for a chance to have one. There are pros and cons of
      being on dialysis versus having a kidney transplant: Dialysis means a 12-hour
      commitment each week, needle sticks, delicate care of your graft or fistula, and
      a careful watch on fluid intake. For transplant patients, flu and infections are
      a constant threat, as is weight gain, bone disease, and the lifetime cost and
      dependency of immunosuppressive medications. But most patients who have a
      transplant--and those who have had one and lost the graft--say they will take the
      risks of dealing with a suppressed immune system over dialysis. Marilyn Buck, a
      recipient of a kidney from her 24-year-old son in 1993, agrees. But it hasn't
      always been easy. Here is her story.

PMID- 9923283
TI  - National Transplantation Pregnancy Registry. Update on pregnancy and renal
      transplantation.

PMID- 9923286
TI  - Should we be more aggressive in honoring a donor's wishes?
AB  - UNOS reported that the number of cadaveric organs procured in 1997 was 5,429,
      virtually unchanged from the previous year. Meanwhile, the number of patients
      waiting for an organ transplant, the majority of them dialysis patients, has
      topped 50,000. How do we make up for the disparity in demand versus the supply?
      The Department of Health and Human Services has announced a new initiative to
      increase donation by 20%. And a new HCFA regulation now requires hospitals to
      report all deaths to its designated organ procurement organization in an effort
      to identify more potential organ donors. The method has proven successful in
      improving organ procurement in two states already. But studies have shown that
      improving organ donation has more deep-seated obstacles: a public that supports
      organ donation in surveys and polls but may not carry through on the actual
      donation when a loved one is a potential candidate, and a medical staff that is
      not trained or remains uncomfortable with asking families to donate at a time of
      grieving. Should we simplify the process and institute presumed consent laws or
      strengthen the legal utility of the organ donor card? In this section, dialysis
      patient Theodore Latour, now awaiting a donor kidney, suggests we take a more
      aggressive approach resembling presumed consent. Two transplant coordinators-
      Alesha Sinclair, RN, CCTC, and Pete Walczak, RN, CCTC--offer a response to his
      views.

PMID- 9923287
TI  - Living donor transplants: how they impact quality of life and family
      relationships?

PMID- 9923288
TI  - HMOs and ESRD: can it work?
AB  - Who wins and who loses in the game of managed care and end-stage renal disease?
      Can capitation fulfill its promise of both improving quality and reducing costs
      in the chronically ill population? In part II of our interview with Ramon G.
      Hannah, MD, MS, the Assistant to the Physician Regional Manager of Operations for
      the Southern California Permanente Medical Group, we discuss the potential for
      pre-ESRD care, how the risks and rewards of capitation could be shared, and what
      quality improvement tools can make an impact on ESRD care. The first part of this
      interview was published in the July issue of NN&I.

PMID- 9923289
TI  - Avoiding the pitfalls when building a new dialysis facility.

PMID- 9923290
TI  - New HCFA rule may impact social work services in ESRD facilities.

PMID- 9923291
TI  - Carve-out contracting for ESRD: what are the opportunities and the risks?

PMID- 9923292
TI  - 1998 U.S. Renal Data System report. Incidence rate remains steady, improvements
      seen in survival.

PMID- 9923293
TI  - A teaching tool for managing hemodialysis access failure.

PMID- 9923294
TI  - Patient centered nephrology: a vanguard approach.

PMID- 9923295
TI  - Cost effectiveness of IDPN therapy measured by hospitalizations and length of
      stay.

PMID- 9923297
TI  - Lundin passes intimate understanding of nephrology onto his patients.

PMID- 9923296
TI  - New dialysis-specific COOP charts may improve ESRD patient assessment.

PMID- 9923298
TI  - Substance abuse and psychiatric issues in transplant recipients and living
      donors.

PMID- 9923299
TI  - The millennium, technology and utopianism.

PMID- 9923300
TI  - Prenatal screening and women's perception of infant disability: a Sophie's Choice
      for every mother.
AB  - Prenatal screening can significantly benefit parents and the community. However,
      it has created a dilemma for women as it requires them to quickly decide whether
      to continue a pregnancy or terminate it should the test indicate a foetal
      abnormality. This can be psychologically traumatic for women torn between their
      connection to an unborn child with all its possible imperfections, and a desire
      to prevent its suffering as a disabled child in later life. A woman must also
      consider her own and her family's future welfare. Extensive research into the
      physical aspects of prenatal screening has not explored the meaning of the
      experience for women or whether termination is the most appropriate option. This
      article examines recent qualitative studies, concluding that women who terminate
      a pregnancy following prenatal screening may experience an acute grief reaction
      or be plagued by guilt and fear that can precipitate marital breakdown.
      Additionally, there is a risk that through striving to eradicate congenital
      disability, a community risks promoting a cult of perfectionism that may have
      discriminatory effects on disabled people.

PMID- 9923302
TI  - A discursive exploration of nursing work in the hospital emergency setting.
AB  - Emergency nurses apply specialist knowledge to the practice of emergency care.
      This paper discusses the ways in which three emergency nurses understand the
      nature of their care from their own frames of reference and experiences and
      presents some of the data collected in a larger study. Various discourses, which
      compete to inform emergency nurses' understandings of practice, are linked with
      the notion of nurses as subjects; that is, each discourse may inform, shape and
      constitute the practice of the nurse and, in turn, the ways in which the patient
      comes to be known and understood. I will examine the ways in which emergency
      nurses come to experience or position themselves vis-a-vis extant forms of
      knowledge of emergency care and the extent to which they articulate new or
      distinctive formulations of emergency care. This paper illuminates the
      commonalities that constitute the discourses of emergency nursing care, and also
      analyse nurses' language which demonstrates that within each discourse
      variations, contradictions and resistances exist. Emergency nursing care occurs
      in a context of a biomedical discourse that dominates, or tends to dominate, the
      work of the emergency setting and so to determine acceptable or possible
      practices. Nevertheless, nurses contest in various ways the 'truths' that they
      understand to underpin their practice. Challenges to biomedical discourses are
      revealed, to some extent, by drawing attention to specific situations and
      particular struggles encountered in emergency nurses' everyday practice.

PMID- 9923301
TI  - Re-framing the representation of women in advertisements for hormone replacement
      therapy.
AB  - This article examines and presents examples of contemporary advertising within
      the medical and health professions that continue the process and organisation of
      knowledge about women and their reproductive bodies. It draws on feminist and
      poststructural perspectives to inform a critical evaluation of the visual
      representations of menopausal women and hormone replacement therapy. These
      representations work to construct certain definitions of the feminine that
      sustain and support existing contradictory cultural meanings and values about
      menopause. I argue that the images continue to misrepresent and define what forms
      of femininity and sexual gender are desirable and acceptable for menopausal
      women. The article addresses the problems of gender discrimination and bias
      within the advertising industry, and illustrates the ways in which readers of
      visual texts may be influenced by stereotypic assumptions concerning a woman's
      lived experience of menopause. It illustrates how specific symbolic images
      directed towards men and women for hormone replacement therapy, testosterone
      deficiency and sexual dysfunction influence the viewer's decision making and
      action responses.

PMID- 9923303
TI  - Exploring the discursive construction of menopause for Thai women.
AB  - The terms 'menopause' and 'mid-life women' have become the subjects of both the
      medical gaze and a billion-dollar industry built by pharmaceutical companies to
      manage the 'problems' of menopause. Menopause is a discursive construction, a
      label that has become endowed with a large number of taken-for-granted
      assumptions about physical and psychological symptoms, self-image and health
      status. These assumptions are based on the medical interests, social
      preoccupations, research and subsequent drug-marketing strategies conducted in
      western societies. Thai society is structured around a different philosophy,
      which has created different meanings for the mid-life woman. This paper explores
      the Western discourses of menopause and the colonizing effect when the
      assumptions underpinning these are imposed on Thai women.

PMID- 9923304
TI  - Phenomenologies as research methodologies for nursing: from philosophy to
      researching practice.
AB  - This paper is concerned with the popularity of phenomenologies and the tensions
      that arise from their use as research methodologies in nursing. Among these
      tensions are: the troublesome issues of adapting a fundamentally philosophical
      means of understanding human being(s) for use as a more pragmatic and robust
      research approach in a practice discipline; the various types of phenomenology
      and the confusions that surround these and other interpretive methodologies,
      particularly within different intellectual and cultural traditions; and the need
      for nursing to find a space in which it can give voice to aspects of its practice
      that are silenced in less existentially oriented methodologies. Although
      phenomenologies are currently popular and possibly fashionable in nursing, there
      are important issues in relation to their use in a methodological sense that
      remain to be addressed.

PMID- 9923306
TI  - 6th International Nurse Practitioner Conference.

PMID- 9923305
TI  - Confronting famine: the case of the Irish Great Hunger.

PMID- 9923307
TI  - Inaugural conference of the Case Management Society of Australia. Case
      management: the critical link.

PMID- 9923308
TI  - Third Nursing Academic International Congress.

PMID- 9923309
TI  - Marie-Francoise Colliere.

PMID- 9923310
TI  - Using anthropology to analyse healthcare situations.
AB  - An anthropological approach to caring has much to offer practising health
      workers, especially nurses. While its attitude towards knowledge differs from
      that used in much traditional medical and clinical education, its capacity to
      draw on the observations and life experiences of both carers and those cared for
      in the design of care plans can provide insights and information crucial to
      recovery and to an extended healthy life. This article models Claude Levi
      Strauss' structural anthropological method within nursing care situations.

PMID- 9923311
TI  - Marie-Francoise Colliere--nurse and ethnohistorian: a conversation about nursing
      and the invisibility of care. Interview by Jocalyn Lawler.

PMID- 9923312
TI  - Truth, virtue and beauty: midwifery and philosophy.
AB  - In this paper, we outline three moments in the history of Western philosophy-
      Classical Greek, Modernity, Postmodernity--and the ways in which issues of truth,
      virtue and beauty have been understood within these philosophical formations. In
      particular, we investigate the ways in which notions of truth, virtue and beauty
      influenced the orthodoxy of birthing practices at these different moments.
      Finally, we examine current, critical reflections on the role of the intellectual
      in postmodern society and use these reflections as a heuristic for understanding
      the role of the contemporary midwife. We suggest that midwifery must reconcile
      two divergent demands. The first is to mobilise the positive, instrumental
      benefits of Western medical science to improve mortality and morbidity outcomes.
      The second is to remain sensitive to the cultural and social meanings attached to
      traditional birthing practices and to understand the roles these play in the well
      being of mother and child.

PMID- 9923313
TI  - Hermeneutic philosophy. Part I: Implications of its use as methodology in
      interpretive nursing research.
AB  - Increasingly, nurses use the philosophy of hermeneutics, especially Heideggerian
      and Gadamerian hermeneutics, to inform interpretive research. However,
      application of the work of these philosophers to interpretive nursing research
      has proved problematic as it fails to recognise, or act upon, obligations
      inherent in their work. Through a review of hermeneutically informed nursing
      research, methodological implications regarding the use of hermeneutic philosophy
      are examined in relation to: (i) the need to address forestructures and pre
      understandings; (ii) checking interpretations with research participants; (iii)
      seeking objectivity, consensus and accuracy in textual interpretation; (iv)
      evaluating interpretations; and (v) gaining entry into the hermeneutic circle.
      This review suggests that despite obligations inherent in Heideggerian and
      Gadamerian hermeneutic philosophy, nurses fail to actualise these obligations in
      their research. In following Heidegger, nurses need to make the scientific theme
      secure by working out their forestructures in terms of the phenomenon under
      investigation. Those following Gadamer need to accept that interpretation seeks
      to manifest textual meanings rather than individual ones. And, whether following
      Heidegger or Gadamer, the way to make manifest textual meanings is to engage with
      the text within the hermeneutic circle by continuing to address forestructures
      and pre-understandings and by considering their influences upon the research.

PMID- 9923314
TI  - Student experiences of nursing health promotion practice in hospital settings.
AB  - It has become evident that the current approaches to health care are inadequate
      for the changing needs of the world. Health promotion has gained recognition as a
      preferred option and many nursing programmes throughout the world have reoriented
      their curricula to incorporate this approach. This paper describes a study that
      was conducted to explicate student experiences of the practice of health
      promotion. Twenty-four students participated in the study; qualitative methods,
      narrative accounts and reflective journals were used to collect the data and the
      data was analysed using van Manen's recommendations for thematic analysis. Three
      major themes emerged: the centrality of caring; empowerment--power, participation
      and partnerships; and the primacy of people. Student narratives are used to
      illustrate the themes.

PMID- 9923315
TI  - Idealised versus tainted femininity: discourses of the menstrual experience in
      Australian magazines that target young women.
AB  - Information and messages concerning health-related issues are not confined to
      material provided by official figures or sources. Much information exists in the
      community and comes from a variety of sources. One such source is the media. This
      paper reports the findings of a study conducted over a 12-month period of
      advertisements for menstrual products in a selection of four monthly Australian
      magazines (n = 48) directed towards young women. The study examined the way in
      which menstruation and the menstrual experience were depicted in terms of page
      space, textual content and visual images. Findings revealed that advertisements
      for menstrual products provided confusing, conflicting and paradoxical messages.
      These included stressing the normality of menstruation while also emphasising the
      importance of keeping it hidden and secret. Menstruation was depicted as being a
      state of tainted (idealised) femininity because of the potential for the
      menstrual silence to be shattered by people finding out. Protection failure was
      depicted as being the ultimate in tainted femininity and a result of a woman's
      incorrect choice of product. Choosing menstrual-care products was depicted as
      simple but, paradoxically, complex and confusing. Women were depicted as
      liberated and sophisticated but images and language related to infancy were used.
      Freedom and liberation were conferred by the use of the advertised product.
      Overall, in common with previous studies, menstruation was depicted as a crisis
      of hygiene that is a risk to femininity. Advertisements for pantyliners suggest
      that femininity itself poses a threat to (idealised) femininity. This study
      demonstrates the crucial role of the media as a source of health information for
      young women.

PMID- 9923316
TI  - Medical science, nursing, and the future.
AB  - Drawing on the work of Evelyn Fox Keller, this paper examines the notion of
      'objectivism' and suggests that medicine as a science is premised upon the denial
      of common mortality. Alternative models for medicine are then examined, including
      the 'romantic science' of Oliver Sacks, and the paper concludes with a brief
      discussion of nursing as a key concept in the articulation of a more
      comprehensive medicine of the future.

PMID- 9923318
TI  - Nursing: the missing ingredient in nurse practitioner education.

PMID- 9923317
TI  - Tolerance in ambiguity: supporting the donor family.

PMID- 9923319
TI  - Complexity and nursing science.

PMID- 9923320
TI  - Unique nursing research methods: the diversity chant of pioneers.

PMID- 9923321
TI  - Standards of nursing and the winds of change.

PMID- 9923322
TI  - Rising above "Drowning in eclecticism".

PMID- 9923324
TI  - The threat of drowning in eclecticism

PMID- 9923323
TI  - Critique of "Drowning in eclecticism".

PMID- 9923325
TI  - Korean adolescents' experiences of smoking cessation: a prelude to research with
      the human becoming perspective.
AB  - Smoking cessation has been identified as an important factor for health and
      quality of life in Korean society. This article explicates Korean adolescents'
      experiences of smoking cessation from the perspective of Parse's human becoming
      theory, as a prelude to conducting research. A nurse was truly present with
      individual students as they shared their experiences of trying to stop smoking.
      Interpreted through the principles and concepts of Parse's theory, the experience
      of quitting smoking is elucidated as a struggle of choosing one's value
      priorities amid the opportunities and limitations inherent in this decision,
      while moving with unique patterns of relating. Staying with the commitment to
      stop smoking is changing one's health and quality of life. The authors briefly
      discuss the implications of this perspective for nursing practice, and identify
      struggling to change as a phenomenon for future research.

PMID- 9923326
TI  - Newman's theory of health as expanding consciousness: research on family
      caregiving in mental illness in Japan.
AB  - The purpose of this study was to apply Newman's theory in family caregiving
      situations in mental illness in Japan. The researcher chose the methodology of
      Newman's theory of health as expanding consciousness because of the good fit
      between Newman's model and the Japanese mindset. The study has provided support
      for the propositions the researcher had entertained prior to embarking on the
      field study. Newman's theory of health as praxis proved to be a viable
      methodology for this population in Japan. The findings support the premise of
      Newman's theory of the person-environment interaction patterns. As a result of
      pattern viewing, the majority of the participants in the study saw possibilities
      for action and decided to act themselves or on behalf of their sick relatives.

PMID- 9923327
TI  - The relationship of self-concept and self-care in children with cancer.
AB  - The purposes of this descriptive study were to examine the relationships between
      self-concept and (a) self-care, (b) dependent-care, and (c) basic conditioning
      factors for children with cancer, and to compare the self-concept of children on-
      and off-therapy. The theoretical framework was Orem's self-care deficit theory of
      nursing. The sample consisted of 74 children with cancer and their mothers.
      Results showed small but significant correlations between variables, providing
      some evidence that if children had higher self-concept scores they performed more
      self-care activities and received more dependent-care from their mothers. The
      self-concept scores of the on- and off-therapy groups were not significantly
      different. This study supports Orem's theory and reinforces the need to promote
      positive self-concept.

PMID- 9923329
TI  - Evidence-based nursing boils down to in the end.

PMID- 9923330
TI  - Ask the family.

PMID- 9923328
TI  - The efficacy of therapeutic touch for improving functional ability in elders with
      degenerative arthritis.
AB  - The purpose of this Rogerian study was to determine whether therapeutic touch
      improved functional ability in elders with arthritis as compared to routine
      treatment and progressive muscle relaxation. Eighty-two non-institutionalized
      elders were randomly assigned to therapeutic touch or progressive muscle
      relaxation treatments. Subjects served as their own control for 4 weeks, then
      received six treatments at 1-week intervals. Pain, tension, mood, and
      satisfaction improved after therapeutic touch and progressive muscle relaxation.
      Hand function improved after therapeutic touch; walking and bending improved
      after progressive muscle relaxation. Functional ability was significantly
      different between the two groups for mobility and hand function. Lower scores
      (indicating better function) were attained by the therapeutic touch group.

PMID- 9923331
TI  - Standing his ground. Interview by Heather Stephen.

PMID- 9923332
TI  - Doing the sums.

PMID- 9923333
TI  - Terra incognita.

PMID- 9923335
TI  - The Christine Hancock column.

PMID- 9923334
TI  - Back to the future.

PMID- 9923336
TI  - Is there a nurse on board?

PMID- 9923337
TI  - Red lights.

PMID- 9923338
TI  - Food for thought. Interview by Ruth Lancaster.

PMID- 9923340
TI  - Every patient deserves a nurse.

PMID- 9923339
TI  - Looking for new ways on pay.

PMID- 9923341
TI  - All together now.

PMID- 9923342
TI  - Living with sickle cell pain.

PMID- 9923343
TI  - Nocturnal enuresis should not be ignored.
AB  - Doctors often dismiss nocturnal enuresis--bedwetting--as a minor problem and
      suggest that the child will 'grow out of it'. Bedwetting can damage the child's
      self-esteem, with long-lasting consequences. Given the range of psychological and
      pharmacological measures available to manage nocturnal enuresis, such a
      conservative approach is unacceptable. These measures are outlined and discussed
      in this article.

PMID- 9923344
TI  - A day surgery post-operative telephone call line.
AB  - The surgical day case unit (SDCU) at Bumley General Hospital recently piloted a
      post-operative telephone service. All patients are called by a registered nurse
      the day after discharge. Audit of the service over six months generated valuable
      information about many aspects of the service, including the incidence of post
      operative problems, pain control and instructions given to patients. The results
      were fed back to staff, who set standards to highlight areas where improvement
      and changes in practice were appropriate.

PMID- 9923345
TI  - How theatre nurses perceive their role: a study.
AB  - The current economic climate makes it increasingly likely that the role of nurses
      in the operating theatre will be scrutinised once again. This article reports on
      how theatre nurses view their work, making some recommendations to try to improve
      the perception of theatre nursing outside operating departments.

PMID- 9923346
TI  - Nursing's nutritional responsibilities.
AB  - This article describes nutrition assessment, focusing on the nurse's nutrition
      responsibilities as a member of the multidisciplinary team.

PMID- 9923347
TI  - Why evidence-based nursing.

PMID- 9923348
TI  - RCN guideline on the management of leg ulcers.
AB  - The treatment of uncomplicated leg ulcers has not always been carried out
      effectively. In this article, the authors introduce an evidence-based clinical
      guideline for the treatment of uncomplicated leg ulcers and highlight some of the
      key recommendations. This is to be launched at Nursing Standard's conference on
      evidence-based nursing this week.

PMID- 9923349
TI  - 'Nurse education is one of those areas where nearly everyone has a strong
      opinion, but not necessarily the same strong opinion as everyone else'.

PMID- 9923350
TI  - Devaluing our profession.

PMID- 9923351
TI  - Pay claim up in Eire.

PMID- 9923352
TI  - Every nurse's business.

PMID- 9923353
TI  - Risks and rights.

PMID- 9923354
TI  - Busy doing quite a lot!

PMID- 9923355
TI  - Health of a nation.

PMID- 9923356
TI  - Within these walls. Interview by Frances Pickersgill.

PMID- 9923357
TI  - Viagra: the facts behind the hysteria.

PMID- 9923358
TI  - Nurse consultant in erectile dysfunction.

PMID- 9923359
TI  - The state of US health insurance.

PMID- 9923360
TI  - The RCN strategy on clinical guidelines.
AB  - There is increasing interest in the potential of clinical guidelines to improve
      the quality of health care. In this report, Lesley Duff outlines areas of
      activity currently being undertaken by the RCN Institute to address these needs.

PMID- 9923362
TI  - The role of the research and development officer.
AB  - This article describes some of the barriers to professional development and
      discusses how research and development (R&D) officers can overcome these and
      support their colleagues in clinical practice.

PMID- 9923361
TI  - Diabetes mellitus types 1 and 2: an overview.
AB  - Large numbers of the population have diagnosed or undiagnosed diabetes. Nurses
      must, therefore, be able to understand the rationale for treatment. Here, the
      author reviews diagnosis, monitoring and the importance of continuing education
      for patients with this condition.

PMID- 9923363
TI  - How to keep student nurses motivated.
AB  - Student nurses on a pre-registration diploma Project 2000 course were poorly
      motivated, skipped lecturers and presented substandard work. This article
      describes how implementing formative assessment and learning contracts helped to
      improve students' attendance, performance and presentation.

PMID- 9923365
TI  - The NHS in winter.

PMID- 9923366
TI  - Snowed under.

PMID- 9923364
TI  - Sexuality in the lives of older people.
AB  - This article aims to explore some of the physical, psychological and social
      aspects of sex and sexuality in later life. It hopes to raise nurses' awareness
      and understanding of sexuality in older people.

PMID- 9923367
TI  - Shock therapy.

PMID- 9923368
TI  - Women's business.

PMID- 9923369
TI  - Nursing is not about to be relieved of it's scapegoat status.

PMID- 9923370
TI  - Down in the mouth.

PMID- 9923371
TI  - Nurse training fails oral exam.

PMID- 9923372
TI  - All mouth.

PMID- 9923373
TI  - Decline and fill.

PMID- 9923374
TI  - Facing cancer.

PMID- 9923376
TI  - Shattered dreams.

PMID- 9923375
TI  - Pick of the bunch.

PMID- 9923377
TI  - Then and now: the changing face of health care.

PMID- 9923378
TI  - Fighting to die with dignity. Interview by Janet Snell.

PMID- 9923379
TI  - Injection technique intravenous--2.

PMID- 9923380
TI  - More safe, less sorry.

PMID- 9923381
TI  - A simple colposcopy examination turned into a nightmare.

PMID- 9923382
TI  - Guillain-Barre syndrome.

PMID- 9923383
TI  - The effectiveness of nursing care after discharge from hospital.
AB  - Increasing pressures on health care services point to a growing role for post
      discharge nursing care. Yet, the evidence concerning such aftercare services has
      been questioned. This article discusses a systematic review of research on the
      effectiveness of nursing care after discharge from hospital. The review shows
      that such care provides no additional benefits compared with usual care.

PMID- 9923384
TI  - Shared governance as a way to involve staff in decision-making.
AB  - Increasing the involvement of clinicians in decision-making is a key part of
      recent NHS policy. One model designed to increase involvement is shared
      governance. This article describes the approach to shared governance developed at
      Kettering General Hospital. Ongoing evaluation of the scheme suggests benefits in
      terms of personal and professional development for those involved.

PMID- 9923385
TI  - Diagnosing and treating genital herpes.

PMID- 9923386
TI  - A back-breaking workload.

PMID- 9923387
TI  - It's time to turn the tide.

PMID- 9923388
TI  - Confronting crises on the home front.

PMID- 9923390
TI  - Nurses fight their corner.

PMID- 9923389
TI  - How assertive should outreach be?

PMID- 9923391
TI  - From Sydney to Siberia.

PMID- 9923393
TI  - Oral hygiene in the elderly: a nursing practice challenge.

PMID- 9923392
TI  - Focus groups: giving voice to the community.

PMID- 9923394
TI  - Reliability and validity of the social abilities component of an Abilities
      Assessment Instrument.

PMID- 9923395
TI  - Back massage can reduce anxiety of elderly residents in long-term care
      institutions.

PMID- 9923396
TI  - Vacuum-assisted closure: wound care technology for the new millennium.

PMID- 9923397
TI  - A pharmacological and HPLC analysis of the excitatory transmitter of the cardiac
      ganglion in the heart of the isopod crustacean Bathynomus doederleini.
AB  - In crustacean neurogenic hearts, the myocardium contracts under the tight control
      of rhythmically active neurons of the cardiac ganglion located inside the heart.
      We demonstrated that the myocardium of Bathynomus doederleini was sensitive to
      glutamate, quisqualate, and kainate, and that the tension of myocardial cells
      developed in a dose-dependent manner. The threshold concentrations were 10(-5) M
      for quisqualate, 10(-4) M for glutamate, and 3 x 10(-4) M for kainate.
      Concanavalin A, known to prevent desensitization of glutamate receptors at
      crustacean neuromuscular junctions, augmented excitatory junctional potentials
      evoked by the cardiac ganglionic neurons in myocardial cells. Using a high
      performance liquid chromatography (HPLC), we analyzed glutamate in extracts of
      the cardiac ganglion and myocardium. We obtained values for glutamate
      concentrations, 8741.2 +/- 184.2 and 678.2 +/- 10.7 pmol/mg, respectively.
      Although we attempted to measure monoamines in the extracts by HPLC, these were
      not detected at measurable (more than 1 fmol per 10-microL sample) levels. In
      conclusion, myocardial cells in isopod crustaceans were suggested to receive
      glutamatergic motor innervation.

PMID- 9923398
TI  - Positive inotropy due to lowering cyclic GMP is also mediated by increases in
      cyclic AMP in control and hypertrophic hearts.
AB  - The aim of the current study was to determine if lowering myocardial cyclic GMP
      by guanylate cyclase inhibition would add independently to the positive inotropic
      effects caused by raising cyclic AMP and if these effects are modified in left
      ventricular hypertrophy (LVH) produced by aortic valve plication. Isoproterenol
      (ISO) (0.1 mg x kg(-1) x min(-1)) was infused into a branch of the left anterior
      descending coronary artery of seven control and eight hypertrophy open-chest
      anesthetized dogs. After 10 min, simultaneous infusion of methylene blue (MB) (2
      mg x kg(-1) x min(-1)) was initiated at the same site. Hypertrophy increased
      heart weight and heart weight/body weight ratio. While both drugs increased left
      ventricular dP/dt(max), no additional global effects were observed in either
      group. Changes in regional variables followed the same pattern in both groups,
      i.e., ISO produced an increase that was enhanced by the addition of MB. ISO
      increased segment shortening, with a significant change in the control group. ISO
      increased regional force in both groups. The addition of MB increased force above
      ISO levels, with a significant change in the LVH group. ISO increased regional
      minute work (g x mm x min(-1)) (control, 1779 +/- 428 to 2541 +/- 500; LVH, 1157
      +/- 253 to 1839 +/- 404) and O2 consumption. MB further increased regional work
      (control, 2993 +/- 952; LVH, 2416 +/- 853) and O2 consumption. ISO raised cyclic
      AMP (pmoles x g(-1)) (control, 468 +/- 41 to 580 +/- 84; LVH, 445 +/- 43 to 562
      +/- 71) and had no effect on cyclic GMP (pmoles x g(-1)) (control, baseline 3.27
      +/- 0.22, ISO 2.87 +/- 0.23; LVH, baseline 6.84 +/- 1.12, ISO 5.66 +/- 0.54). The
      addition of MB lowered cyclic GMP (control, 2.41 +/- 0.26; LVH, 3.68 +/- 0.35),
      but also increased cyclic AMP (control, 1021 +/- 121; LVH, 1107 +/- 134). Similar
      results were observed in control hearts using a specific soluble guanylate
      cyclase inhibitor (ODQ) in terms of changes in local work, O2 consumption, and
      cyclic nucleotides. Thus, at least part of the positive inotropic response to
      lowering cyclic GMP was mediated by changes in cyclic AMP in the current model.
      This was true in both control and LVH animals, although baseline cyclic GMP
      levels were higher, and a larger reduction in cyclic GMP was observed with MB in
      the LVH group.

PMID- 9923399
TI  - Minoxidil accelerates heart failure development in rats with ascending aortic
      constriction.
AB  - To test the ability of the heart to express characteristic geometric features of
      concentric and eccentric hypertrophy concurrently, constriction of the ascending
      aorta was performed in 4-week-old rats. Simultaneously, these rats were treated
      with an arteriolar dilator minoxidil. An examination 6 weeks after induction of
      the hemodynamic overload revealed no signs of congestion in systemic or pulmonary
      circulation in rats with aortic constriction or minoxidil-treated sham-operated
      rats. The magnitude of hemodynamic overload caused by aortic constriction or
      minoxidil treatment could be considered as equivalent, because the same
      enlargement of left ventricular pressure-volume area was necessary to compensate
      for either pressure or volume overload. Myocardial contractility decreased in
      rats with aortic constriction, and the compensation was achieved wholly by the
      marked concentric hypertrophy. Volume overload in minoxidil-treated rats was
      compensated partially by the eccentric hypertrophy and partially by the increased
      myocardial contractility. In contrast, increased lung weight and pleural effusion
      were found in all minoxidil-treated rats with aortic constriction. Unfavorable
      changes in left ventricular mass and geometry, relatively high chamber stiffness,
      and depressed ventricular and myocardial function were responsible for the
      massive pulmonary congestion.

PMID- 9923400
TI  - Long-term supplementation of culture medium with essential fatty acids alters
      alpha-linolenic acid uptake in Caco-2 clone TC7.
AB  - We investigated the influence of four different culture media: 20% fetal bovine
      serum (FBS), 5% FBS, 5% FBS supplemented with 10 mg x L(-1) linoleic acid (18:2(n
      6)) or alpha-linolenic acid (18:3(n-3)) on alpha-linolenic acid apical uptake in
      clone TC7 of human intestinal Caco-2 cell line. Neither cellular viability nor
      cell monolayer integrity and permeability were altered by the four culture
      conditions. Our results show that the different culture media led to changes in
      alpha-linolenic acid maximal rate of uptake (Vmax) but did not alter the apparent
      transport constant (Km). Reducing FBS concentration from 20% to 5% increased
      significantly the rate of alpha-linolenic acid uptake, which was further
      increased by supplementation of the medium with 18:2(n-6) or 18:3(n-3).
      Supplementation with essential fatty acids led to a marked enrichment of brush
      border membrane phospholipids in polyunsaturated fatty acids of the corresponding
      series and decreased significantly the levels of monounsaturated fatty acids.
      Saturated fatty acids, unsaturation index, and cholesterol/fatty acid ratios were
      unchanged. No clear relation could be established between the changes in membrane
      lipid composition and the alterations of alpha-linolenic acid uptake. These
      results indicate a weak influence of membrane lipid composition in the modulation
      of the uptake. Therefore, the increase of uptake following long-term
      supplementation of TC7 cells with essential fatty acids could be attributed to an
      increase of the expression of membrane protein(s) involved in the apical uptake
      of long-chain fatty acids. This remains to be established.

PMID- 9923401
TI  - Conduction block in Purkinje fibers by homogeneous versus localized decrease of
      the gap junction conductance.
AB  - Gap junction channels provide the pathway for the cell-to-cell propagation of
      cardiac action potential. Impairment of junctional conductance decreases
      conduction velocity and can cause block, two conditions that favor ventricular
      arrhythmias and fibrillation by re-entrant excitation. These experiments were
      designed to examine the effects of homogeneous versus localized decrease of the
      gap junction conductance on propagation of action potential in Purkinje fibers
      from sheep hearts. The fibers were mounted in a three-compartment chamber, and
      cell-to-cell conductance was progressively reduced by applying heptanol either
      over a central 2-mm segment or over the whole fiber length. The internal
      resistivities (Ri) at which conduction of the action potential became blocked
      were determined in both cases. With 3.5 mM heptanol in the central compartment,
      conduction failed when Ri was increased by only 3-4.6 times the control values.
      In contrast, when the same concentration of heptanol was added simultaneously to
      all three compartments, Ri had to rise by a factor of 7.5-9.4 before conduction
      became decremental and was blocked. In both situations, dV/dt(max) at the time of
      conduction block was similarly decreased to about 50% of the control values.
      Other parameters being equal, a moderate decrease of the gap junction conductance
      and of the fast sodium current, insufficient to block propagation of the action
      potential when they are homogeneously distributed, become sufficient to interrupt
      conduction if the action potential merges abruptly into a portion of fiber with
      normal internal conductivity at the outlet of the area of increased resistance.
      This greater sensitivity to block is accounted for by the increase in electrical
      load at the discontinuity in the core conductor between the region of increased
      internal resistance and the normal part of fiber that follows. Areas of steep
      transition from high to low input resistances of the core conductor, such as may
      develop in localized ischemia, therefore appear particularly susceptible to
      conduction failure.

PMID- 9923402
TI  - Effects of lactate on force production by mouse EDL muscle: implications for the
      development of fatigue.
AB  - Numerous studies suggest that the accumulation of lactate during exercise
      contributes to the fatigue process. This notion is based on close negative
      correlations between force and intracellular muscle lactate concentrations during
      fatigue and recovery. In this investigation, we attempted to determine if lactate
      directly affects muscle force output. This was accomplished by incubating mouse
      extensor digitorum longus muscles in extracellular concentrations of 10, 20, 30
      and 50 mM L-(+)-lactate at 21 and 37 degrees C and monitoring force output. At 21
      degrees C, 30 and 50 mM, extracellular lactate significantly reduced tetanic
      force (Po 250 ms, 100 Hz) to 95 and 93% of initial, respectively. In addition,
      the rate of force development (+dP/dt) was reduced to 93 and 89% of initial. At
      37 degrees C, the effects of extracellular lactate were augmented as Po was
      reduced to 73 and 62% of initial and +dP/dt was reduced to 55 and 44% of initial
      at 30 and 50 mM, respectively. We next sought to determine if the reduction in Po
      was due to altered sarcoplasmic reticulum (SR) function using a muscle homogenate
      fraction. The rate of AgNO3-induced SR Ca2+ release was depressed by 31% in the
      presence of 25 mM lactate. These results suggest that elevated lactate depresses
      force production by whole muscle and may play some role in the fatigue process.
      In addition, it appears that lactate depresses force production, in part, by
      inhibiting Ca2+ release from the SR.

PMID- 9923403
TI  - Effect of cyclic AMP on the calcium-dependent potassium conductances of rat
      Leydig cells.
AB  - Two potassium conductances have been isolated in rat Leydig cells by their
      sensitivity to cytosolic calcium and to K+ channel blockers. We used the whole
      cell configuration of the patch-clamp technique to investigate their sensitivity
      to cyclic AMP, the main messenger of luteinizing hormone, which stimulates Leydig
      cell steroidogenesis. The voltage-dependent potassium conductance is not modified
      by exposing the cell to 1 mM chlorophenylthio-cyclic AMP (CPT-cAMP), a membrane
      permeant analogue of cAMP. By contrast, the large, calcium-activated potassium
      conductance is upregulated by CPT-cAMP. Furthermore, the latter is potentiated by
      the chloride channel blocker 4-acetamido-4'-isothiocyanato-stilbene-2,2'
      disulfonic acid, sodium salt (SITS).

PMID- 9923404
TI  - Novel attributes of an androgenic steroid-mediated increase in cardiac end
      diastolic stiffness in rats.
AB  - Although cardiac early and mid-diastolic stiffness constants are well accepted as
      being modulated by alterations in myocyte active processes, increments in left
      ventricular end diastolic (LVED) stiffness (LVED k; g x cm(-2)) in classical
      pathological models of a reduced LVED k (e.g., diabetes mellitus (DM) and
      hypertension) are determined largely by the properties of the myocardial
      extracellular matrix (ECM). As such, increases in LVED k in the latter cardiac
      pathologies are insensitive to acute changes in cardiac load, heart rate, and
      contractility. We examined whether the same attributes that apply to changes in
      LVED k in DM and in spontaneously hypertensive rats (SHRs) also apply to an
      androgenic steroid (nandrolone decanoate; 5 mg x kg(-1) biweekly) induced
      increase in LVED k. Myocardial collagen (ECM) characteristics and the capacity of
      acute verapamil-mediated changes in cardiac dynamics to impact on LVED k were
      evaluated after 3 months of steroid treatment to rats, 4 months of DM in rats,
      and in 45-week-old SHRs. Chronic steroid administration increased LVED k (steroid
      = 42 +/- 4, control = 25 +/- 2; p < 0.01). An acute infusion of verapamil to
      steroid-treated rats decreased LVED k to values not different from controls (29
      +/- 3; p < 0.05 as compared with LVED k at baseline). Measures of myocardial
      collagen concentrations, phenotype ratios, and cross-linking were unchanged
      following steroid administration. Verapamil failed to alter the increased LVED k
      that occurs in either rats with DM or in SHRs, despite similar effects on cardiac
      dynamics as those noted in steroid-treated rats. The increased LVED k in the
      former animal models was associated with alterations in the ECM. In conclusion,
      the unique lack of association of the androgenic steroid-induced increase in LVED
      k with alterations in the myocardial ECM and the novel sensitivity of the steroid
      mediated increment in LVED k to acute alterations in cardiac dynamics further
      supports the notion that changes in LVED k should not be considered to be a
      reflection of ECM characteristics in all cardiac conditions.

PMID- 9923405
TI  - Role of NO and angiotensin II in the early development of endothelial functions
      impairment and cardiac hypertrophy in deoxycorticosterone acetate-salt
      hypertension.
AB  - This study was designed to investigate the effects of chronic inhibition of NO
      synthesis as well as chronic angiotensin receptor blockade with losartan in the
      development of hypertension, on mesenteric arterial bed reactivity as well as on
      the development of cardiac and kidney hypertrophy in deoxycorticosterone-salt
      (DOCA) hypertension. Uninephrectomized rats were divided in four experimental
      groups all receiving saline water to drink and treated or not with losartan over
      a period of 9 days. Two of these groups were administered DOCA, one of which
      received also N(G)-nitro-L-arginine-methyl ester (L-NAME) to drink. A third group
      received only L-NAME, while another group received only saline. Systolic blood
      pressure was similarly increased in L-NAME, DOCA, DOCA-L-NAME groups. Cardiac and
      kidney weights were increased in DOCA but significantly reduced in DOCA-L-NAME.
      Losartan prevented the development of hypertension in all groups and also
      prevented cardiac and kidney hypertrophy in DOCA. The hyperreactivity of
      mesenteric arteries to phenylephrine, measured in the presence of indomethacin,
      was endothelium-dependent in both L-NAME groups but not in DOCA rats.
      Pretreatment with BQ 123 did not modify these endothelium-dependent responses in
      L-NAME rats. Chronic losartan prevented endothelium-dependent phenylephrine
      hyperreactivity only in DOCA, whereas only the removal of the endothelium
      attenuated the responsiveness in both L-NAME-treated groups. Vasorelaxations to
      acetylcholine and isoproterenol were attenuated in the three hypertensive groups
      and were normalized only in DOCA and L-NAME treated with losartan. In summary, in
      all hypertensive groups, blood pressure was normalized by losartan independently
      of its effects on endothelial functions. In DOCA, losartan normalized the
      phenylephrine hyperreactivity through an endothelial-dependent mechanism.
      However, in L-NAME-treated groups an endothelial-derived contracting factor,
      other than angiotensin II, endothelin, or vasoconstrictor prostanoids, appears to
      be activated. Both NO and angiotensin II seem to play a role in the early
      development of hypertension and organ hypertrophy in DOCA hypertension.

PMID- 9923406
TI  - Effects of alpha1-antagonists on production and release of aldosterone and other
      steroid hormones by porcine adrenocortical cells in vitro.
AB  - Quinazoline type alpha1-adrenoceptor antagonists (range 10-100 microM) inhibited
      aldosterone release of a cell suspension of porcine adrenocortical cells, potency
      order: doxazosin > prazosin > trimazosin. Phenoxybenzamine also inhibited the
      aldosterone release at a concentration of 100 microM. Alpha1-adrenoceptor
      antagonists from other chemical classes had no measurable effect on the
      aldosterone output from adrenocortical cells in vitro. Agonists selective for
      either alpha1- or beta-adrenoceptors did not affect the aldosterone release. The
      inhibition of the aldosterone release induced by quinazolines was similar with
      different substrates. The small differences between the drug-induced inhibitions
      could be ranked as corticosterone = progesterone > pregnenolone =
      deoxycorticosterone. The doxazosin (10 microM)-induced changes in the release of
      nine steroids indicated that quinazoline-type alpha1-antagonists interfere with
      enzymes of the aldosterone biogenesis pathway involved in C18-oxidation and
      C21beta-hydroxylation, reducing the release of both aldosterone and
      corticosterone. At higher concentrations (100 microM), the C21beta-hydroxylation
      in the cortisol biogenesis pathway is also affected, decreasing the output of
      cortisol and deoxycortisol, but increasing the output of progesterone and OH
      progesterone. Simultaneously, the C17-oxidation and side-chain cleavage is also
      inhibited, decreasing the output of androstenedione. The rank order of
      phenoxybenzamine (100 microM)-induced inhibition of the aldosterone release with
      different substrates is pregnenolone > corticosterone = progesterone >
      deoxycorticosterone. With pregnenolone as substrate, the output of aldosterone,
      corticosterone, and cortisol was reduced to the same extent. The
      dehydroepiandrosterone, androstenedione, and progesterone release was enhanced.
      It seems that phenoxybenzamine is a rather selective inhibitor of the
      mitochondrial P450(11beta/18) enzymes.

PMID- 9923407
TI  - Tachykinins mediate noncholinergic excitatory neural responses in the circular
      muscle of rat proximal colon.
AB  - Using the sucrose-gap technique, we attempted to assess a role for tachykinins
      (TKs) in mediating noncholinergic excitatory junction potential (EJP) and
      contraction, in the circular muscle of rat proximal colon. Excitatory responses
      were evoked by submaximal electrical field stimulation (EFS) in the presence of
      atropine (1 microM), guanethidine (1 microM), indomethacin (10 microM), and
      N(omega)-nitro-L-arginine methyl ester (L-NAME) (100 microM). The NK1 receptor
      antagonist, SR 140,333 (up to 3 microM) or the NK2 receptor antagonists, SR
      48,968 and MEN 10,627 (up to 5 microM) produced a partial inhibition of the
      excitatory responses to EFS. The co-administration of the selective NK1 and NK2
      receptor antagonists produced additive effects on the responses to EFS. Selective
      NK1 receptor agonist, [Sar9, Met (O2)11]-substance P, induced depolarization and
      contraction, antagonized by SR 140,333, but not by NK2 receptor antagonists. NK2
      receptor agonist, [betaAla8]-neurokinin A (4-10), also produced electrical and
      mechanical excitatory effects that were antagonized by SR 48,968 or MEN 10,627,
      but not by the NK1 receptor antagonist. Our results provide evidence that, in
      circular muscle of rat colon, endogenous tachykinins are the main excitatory
      transmitters for nonadrenergic, noncholinergic (NANC) excitation and their action
      is mediated by both NK1 and NK2 receptors.

PMID- 9923408
TI  - Pharmacological profile of the isomers of the GluR-specific agonist ATPA.
AB  - We have synthesized the (R)- and (S)-isomers of 2-amino-3-(3-hydroxy-5-tert
      butylisoxazol-4-yl) propanoate (ATPA) by stereochemically certain routes. Our
      studies in the rat cortical wedge preparation indicate that (R)-ATPA has no
      observable excitatory effect, while (S)-ATPA has an apparent K(D) of 16 microM.
      This excitatory response is unaffected by the specific N-methyl-D-aspartate
      (NMDA) antagonist, D-2-amino-5-phosphonopentanoic acid (DAP5) but is partially
      blocked by 6-nitro-sulfamoyl[f]quinoxalinedione (NBQX) at concentrations that
      attenuate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate
      (AMPA), the effects are however reduced by the nonspecific antagonist kynurenate
      (KYN), indicating an interaction with a class of kainate receptor.

PMID- 9923409
TI  - Increased gene transfer into human CD34+ progenitor cells using retroviral
      vectors produced by a canine packaging cell line.
AB  - Using retroviral supernatants derived from the amphotropic murine packaging cell
      line PA317 and the amphotropic canine packaging cell line (DA), cord blood and
      mobilized peripheral blood CD34+ cells were transduced with the vector LN
      (neomycin resistance) and the vector L-TR/TAT neo (neomycin resistance in
      conjunction with a double-hammerhead ribozyme conferring anti-HIV activity).
      Different multiplicities of infection (MOI) were applied in the setup according
      to vector titrations on NIH-3T3 cells. PA317-based supernatants were tested at
      MOI of 10 and 30. Purified concentrated DA-derived vector preparations were
      tested at MOI of 10, 30, 100, and 300. Immediately after transduction, CD34+
      cells were plated into colony assays in the presence and absence of G418 to
      evaluate the amount of gene transfer and potential toxic effects of the vectors
      on colony growth. The remaining cells were subjected to G418 selection in liquid
      culture for 12 days and subsequently challenged with HIV-1JR-FL to test for
      efficacy of the anti-HIV gene in macrophages derived from transduced CD34+ cells.
      Transduction by the PA317-packaged vectors was maximal at the lowest MOI used and
      did not increase with increasing MOI. In contrast, transduction by the DA
      packaged vectors could be progressively increased using increased MOI. The net
      transduction efficiency per unit of reverse transcriptase activity in the DA
      vector preparations was 8.7-fold higher than in the PA317 vector supernatants.
      HIV-1 challenge of the cells transduced by the ribozyme vector derived from the
      PA317 packaging cells resulted in a 1.5 log inhibition of p24 output compared
      with the control cells containing neomycin resistance only. A 2.5 log inhibition
      of p24 output could be observed in the cell population transduced with DA
      packaged vector supernatants. Compared with retroviral supernatants from PA317
      packaging cell lines, DA packaging line-derived vector preparations demonstrated
      higher transduction efficiency into CD34+ cells, particularly at higher MOI, and
      increased efficacy of the transferred anti-HIV gene when challenged with HIV-1JR
      FL. The increase in transduction efficiency may be due to a higher ratio of
      intact vs. defective vector particles in the DA-derived vector preparations.

PMID- 9923410
TI  - HLAs and risk of acute graft-vs.-host disease after marrow transplantation from
      an HLA-identical sibling.
AB  - We explored the relationship between individual human leukocyte antigens (HLAs)
      and the risk of acute graft-vs.-host disease (GVHD) after allogeneic marrow
      transplantation from HLA-identical siblings. If the repertoire of polymorphic
      peptides encoded by minor histocompatibility loci is limited such that certain
      major histocompatibility complex molecules might not present any peptides that
      cause GVHD, then certain HLA alleles should be associated with a relatively
      reduced risk of GVHD and others should be associated with a relatively increased
      risk. Contrary to results reported in previous studies, we found no convincing
      evidence for associations between HLA antigens and risk of acute GVHD after HLA
      identical marrow transplantation. These results are consistent with the
      hypothesis that the variety of minor histocompatibility antigens is not
      constrained by the repertoire of peptides collectively encoded by minor
      histocompatibility loci.

PMID- 9923411
TI  - A randomized trial of recombinant human interleukin-11 following autologous bone
      marrow transplantation with peripheral blood progenitor cell support in patients
      with breast cancer.
AB  - This study assessed the safety and efficacy of recombinant human interleukin
      (rhIL)-11 in decreasing platelet transfusion requirements in patients with breast
      cancer who were undergoing autologous bone marrow transplantation (ABMT) with
      peripheral blood progenitor cell (PBPC) support. After high-dose therapy with
      cyclophosphamide, cisplatin, and carmustine, 80 patients were randomized to one
      of three treatment groups: placebo (26), 25 microg/kg of rhIL-11 (28), and 50
      microg/kg of rhIL-11 (26). Of those randomized, 75 (94%) received at least one
      dose of the masked study drug and the remaining 5 (6%) withdrew consent before
      study drug administration. In the placebo group, each patient received an average
      12.4 (+/-10.2) platelet transfusions vs. 9.2 (+/-5.0) in the 25-microg/kg rhIL-11
      group (p = 0.17) and 9.9 (+/-3.5) in the 50-microg/kg rhIL-11 group (p = 0.34).
      There was no statistically significant difference between the rhIL-11 groups and
      the placebo group in the median number of days to platelet recovery. Neutrophil
      and red blood cell recovery were similar for all treatment groups. The imbalance
      in the number of patients already alloimmunized at study entry in the rhIL-11
      groups (12) and in the placebo group (1) may have confounded the primary efficacy
      assessment. Most adverse events were related to the high-dose chemotherapy.
      Generally mild edema and minor conjunctival bleeding (grades 1 or 2) were
      statistically associated with rhIL-11 administration (p < 0.04). There was no
      association between rhIL-11 and the occurrence of atrial arrhythmias, although
      there was a suggestion of an association with rhIL-11, 5 of 50 cases vs. 1 of 25
      in the placebo group. Two cardiovascular events, tachycardia and hypotension
      (grade 1 or 2), occurred in the 50-microg/kg rhIL-11 group. The number of
      patients who discontinued study drug dosing because of an adverse event was
      distributed across all treatment groups. In summary, rhIL-11 was safe and well
      tolerated in this study. The results did not demonstrate that rhIL-11 treatment
      significantly decreased platelet transfusion requirements after high-dose
      chemotherapy with ABMT and PBPC support.

PMID- 9923412
TI  - A prospective randomized double-blind trial of antithrombin III concentrate in
      the treatment of multiple-organ dysfunction syndrome during hematopoietic stem
      cell transplantation.
AB  - Many of the complications of high-dose therapy with hematopoietic stem cells are
      caused by or lead to the multiple-organ dysfunction syndrome (MODS). In
      hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII)
      deficiency is independently associated with MODS to the exclusion of transplant
      type, preparative regimen, and bacteremia. In experimental settings, replacement
      of ATIII can ameliorate the severity of MODS that develops in response to a
      variety of pathologic stimuli, suggesting that ATIII supplementation might
      improve the clinical course of MODS in patients undergoing HSCT. We performed a
      study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine
      patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation
      of <90%), central nervous system dysfunction (drop of >4 points in the mini
      mental status exam), or hepatic dysfunction (bilirubin >34 micromol/L [2.0 mg%],
      weight gain of >5% over baseline, and abdominal pain, possibly of hepatic origin)
      with a concomitant ATIII activity of <84% were double-blind randomized to receive
      ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ
      dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin
      placebo. The group randomized to ATIII had a lower severity-of-illness score
      (15.7 +/- 19.2 vs. 28.6 +/- 25.2, p = 0.03), shorter duration of hospitalization
      (14.9 +/- 16.7 vs. 25.7 /- 17.9 days, p = 0.03), and lower hospital charges
      ($138,700 +/- $23,500 vs. $206,400 +/- $34,000). ATIII concentrate was associated
      with improved morbidity of MODS in patients undergoing HSCT when given early in
      the evolution of the syndrome.

PMID- 9923413
TI  - Prolonged erythroid aplasia after major ABO-mismatched transplantation for
      chronic myelogenous leukemia.
AB  - Erythroid engraftment after non-T cell-depleted allogeneic bone marrow transplant
      (BMT) is reviewed in 112 patients treated for chronic myelogenous leukemia (CML).
      Twenty-two of 76 evaluable patients were transplanted over a major ABO-mismatch
      compatibility barrier. These patients showed an increased delay in erythroid
      engraftment and in time to red blood cell transfusion independence when compared
      with ABO-identical or minor mismatched recipients. No difference in granulocyte
      or platelet engraftment was evident. Erythroid engraftment usually occurred
      spontaneously without specific intervention. One patient was found to have
      erythroid hypoplasia at day 201 after BMT, despite therapy with intravenous
      immunoglobulin and high-dose erythropoietin. An anti-A titer of 16,000 was
      documented. This patient was successfully treated with an aggressive course of 18
      plasmapheresis procedures and with donor-type plasma replacement. Delayed
      erythroid engraftment is common after non-T cell-depleted major ABO-mismatched
      BMT in CML, but rarely requires intervention other than transfusion support. Rare
      cases of refractory erythroid aplasia may be treated without additional
      immunosuppression by aggressive plasma exchange with donor-type plasma.

PMID- 9923416
TI  - On optimizing high-pressure freezing: from heat transfer theory to a new
      microbiopsy device.
AB  - High-pressure freezing (HPF) is currently the only method which enables adequate
      cryoimmobilization of biological samples thick enough to describe the bulk of the
      sample. In the current state of HPF instrumentation and preparation methods, the
      technique has not yet reached its full potential. While suspensions can be
      prepared easily for HPF, tissue preparation is restricted by the need to
      compromise between different requirements and difficulties. (i) In order to
      achieve optimal freezing quality, very thin samples are required. (ii) There is
      mechanical difficulty in cutting such thin samples without distorting the
      organization of the tissue. (iii) The cutting and the succeeding preparation
      steps of small samples require long handling times (minutes), which may result in
      physiological and hence structural alterations. Computerized heat transfer
      simulations are presented which confirm that the efficiency of heat extraction
      from cylindrical samples contained within thin-walled metal tubes is higher than
      from standard flat discoid samples sandwiched between relatively thick aluminium
      platelets. Based on this fact, we developed a prototype of a new microbiopsy
      device which enables the quick excision of such cylinders of soft tissues. The
      device utilizes sharp gold needles of an inner diameter of 200 microm and wall
      thickness of 50 microm. The frozen sample contained in the soft gold needle
      permits all the manipulations needed for conventional cryo-preparation techniques
      for electron microscopy (e.g. cryo-sectioning, freeze-fracturing, freeze
      substitution).

PMID- 9923414
TI  - Relationship of tacrolimus (FK506) whole blood concentrations and efficacy and
      safety after HLA-identical sibling bone marrow transplantation.
AB  - A randomized clinical trial comparing tacrolimus with cyclosporine, both with
      short-course methotrexate, as prophylaxis against graft-vs.-host disease (GVHD)
      in allogeneic HLA-matched sibling bone marrow transplant patients was conducted.
      Cyclosporine was dosed to achieve a target concentration range between 150 and
      450 ng/mL during the first 8 weeks after transplant. For tacrolimus, the target
      concentration range was 10-30 ng/mL during the first 8 weeks after transplant. A
      gradual tapering schedule of 20% per month during months 3-6 was then conducted
      for patients in both treatment arms. The efficacy of the immunosuppressive
      regimen was determined by the rate of acute GVHD grades II-IV The toxicity of the
      immunosuppressive regimen was determined by the occurrence of the creatinine
      exceeding 2 mg/dL, the creatinine doubling the baseline value, or the necessity
      for hemodialysis. Correlations between blood concentrations and efficacy and
      toxicity parameters were assessed. For both tacrolimus and cyclosporine,
      increasing blood concentrations were associated with greater renal dysfunction.
      For cyclosporine, there was a nonsignificant trend to an increased incidence of
      grades II-IV acute GVHD with lower cyclosporine blood concentrations (<300
      ng/mL). In contrast, there did not appear to be a relationship between the blood
      concentrations of tacrolimus and the occurrence of acute GVHD. This suggests that
      optimization of efficacy while minimizing the risk for nephrotoxicity could be
      achieved by dosing tacrolimus to a targeted range between 10 and 20 ng/mL.

PMID- 9923417
TI  - High-pressure freezing for immunocytochemistry.
AB  - Ultrastructural immunocytochemistry requires that minimal damage to antigens is
      imposed by the processing methods. Immersion fixation in cross-linking fixatives
      with their potential to damage antigens is not an ideal approach and rapid
      freezing as an alternative sample-stabilization step has a number of advantages.
      Rapid freezing at ambient pressure restricts the thickness of well-frozen
      material obtainable to approximately 15 microm or less. In contrast, high
      pressure freezing has been demonstrated to provide ice-crystal-artefact-free
      freezing of samples up to 200 microm in thickness. There have been few reports of
      high-pressure freezing for immunocytochemical studies and there is no consensus
      on the choice of post-freezing sample preparation. A range of freeze-substitution
      time and temperature protocols were compared with improved tissue architecture as
      the primary goal, but also to compare ease of resin-embedding, polymerization and
      immunocytochemical labelling. Freeze-substitution in acetone containing 2% osmium
      tetroxide followed by epoxy-resin embedding at room temperature gave optimum
      morphology. Freeze-substitution in methanol was completed within 18 h and in
      tetrahydrofuran within 48 h but the cellular morphology of the Lowicryl-embedded
      samples was not as good as when samples were substituted in pure acetone. Acetone
      freeze-substitution was slow, taking at least 6 days to complete, and gave blocks
      which were difficult to embed in Lowicryl HM20. Careful handling of frozen
      samples avoiding rapid temperature changes reduced apparent ice-crystal damage in
      sections of embedded material. Thus a slow warm-up to freeze-substitution
      temperature and a long substitution time in acetone gave the best results in
      terms of freezing quality and cellular morphology. No clear differences emerged
      between the different freeze-substitution media from immunocytochemical labelling
      experiments.

PMID- 9923418
TI  - Structural changes in samples cryofixed by contact with a cold metal block.
AB  - A common method of cryofixation is to bring a specimen rapidly in contact with a
      cold metal block. It is usually thought that during this process the surface of
      the specimen suffers little distortion since it freezes rapidly. Whether this is
      likely depends on the rate at which samples freeze compared with the speed at
      which the sample hits the cold block. There is some discrepancy between the
      published experimentally and theoretically determined freezing rates. As a
      contribution to this debate the distortion in cryofixed, freeze-substituted,
      striated muscle fibres has been investigated. In transverse sections, compression
      can be detected by deviations of the filament lattice from the hexagonal and used
      to estimate the time of freezing. Some specimens were frozen using a Gatan
      Cryosnapper, which freezes by catching the specimen between two nitrogen-cooled
      copper jaws. In addition, the speed with which the jaws close has also been
      determined. The results suggest that freezing of the well-preserved areas occurs
      in substantially less than 1 ms. This conclusion is supported by results obtained
      using metal-mirror apparatus in which the cushioned specimen was dropped onto a
      nitrogen- or helium-cooled copper block. All the specimens frozen against a cold
      block have a flat edge whereas muscle fibres are round. At the very edge there is
      evidence of structural damage as well as the more general lattice distortion.

PMID- 9923420
TI  - Crystallographic analysis of freeze-fracture electron micrographs: application to
      the structure determination of cubic lipid-water phases.
AB  - An original approach combining freeze-fracture electron microscopy and
      quantitative image processing has been developed as an alternative to X-ray
      analysis. It has been applied to the crystallographic study of different lipid
      water cubic phases [bicontinuous or micellar and of type I (oil-in-water) or type
      II (water-in-oil)] and has enabled significant advances in the study of these
      phases. Freeze-fracture electron microscopy has revealed that the cubic phases
      fracture preferentially along a few crystallographic directions which appeared on
      the images as noisy planar fracture surfaces containing periodic information. The
      visibility of the corresponding unit cells has been considerably improved by
      image-filtering techniques based on correlation averaging, allowing a
      quantitative analysis of the fracture images to be made. This analysis yielded
      faithful information on the symmetries of the cubic structure (rotation axes and
      mirror planes) as well as on the structure of the cubic phase itself. Eventually,
      the different parameters that determine the most favourable fracture pathways
      within the structures were established. This novel approach constitutes a
      powerful tool of general interest, complementary to X-ray diffraction, for
      solving complex ordered macromolecular structures at low resolution.

PMID- 9923419
TI  - A cryoclamp for the rapid cryofixation of the isolated blood-perfused rabbit
      cardiac papillary muscle preparation at predefined times during the contraction
      cycle.
AB  - There is increasing evidence that the distribution of monovalent cations in
      cardiac cells may be non-uniform, particularly in the region immediately beneath
      the sarcolemma, and we have proposed that a build-up of sodium in this region
      could be an important factor in the development of ischaemia-reperfusion injury.
      Electron probe X-ray microanalysis is ideal for the study of such changes in
      distribution but the application of the technique to this problem imposes severe
      requirements on the specimen and on the method for cryofixation. The specimen
      must be perfused through its vasculature so that it can be made truly ischaemic
      and be successfully reperfused. It is necessary to be able to cryofix the
      specimen without disturbance of its blood supply, electrical stimulation or
      temperature. It is also important to know the time in the contraction cycle when
      cryofixation occurs. Here we describe the design of an automated cryofixation
      device which can be used to cryofix a blood perfused papillary muscle preparation
      at predetermined time points in the contraction cycle. Preliminary data obtained
      from the analysis of rabbit papillary muscles subjected to varying periods of
      ischaemia are included as an example of the use of the cryoclamp.

PMID- 9923421
TI  - Effect of isometric contraction on threshold somatosensory evoked potentials.
AB  - We previously described the augmentation of sensory nerve action potential
      amplitudes after near and remote isometric muscle contraction. In this study, we
      wished to determine if the sensory cortex was involved in this process. In this
      prospective, intrinsically controlled study, we studied threshold somatosensory
      evoked potentials in 12 normal subjects with stimulation of the median nerve at
      5.1 Hz. The subjects were tested during the following conditions: baseline, 25%,
      and 75% maximum isometric abductor digiti minimi contraction for 4 min. Each of
      these conditions was recorded before, during, and 4 min and 8 min after
      contraction. Results showed that at 25% contraction, there was a significant
      temporal increase in N9 amplitude (2.1-2.6 microV; P = 0.05, analysis of
      variance, repeated measures) and a decrease in N20 amplitude with 75% contraction
      (1.9-1.6 microV; P = 0.03, analysis of variance, repeated measure). No
      significant changes were noted in the spinal cord or brainstem recordings. In
      conclusion, it appears that augmentation of the brachial plexus peripheral
      nervous system recording occurs concurrently with central inhibitory gating. The
      possibility of peripheral nervous system adaptability will be discussed.

PMID- 9923422
TI  - Survey of injuries and protective gear worn by in-line skaters in public parks.
AB  - In-line skating, also known as rollerblading, has become popular as a
      recreational activity as well as a mode of transportation. Increased
      participation has been accompanied with a marked rise in major and minor
      injuries. The objective of this study was to survey active in-line skaters and to
      describe their demographic features, formal training, protective gear used, and a
      history of incurred injuries. A questionnaire was distributed to randomly
      selected in-line skaters in a large public park in New York City. Of the 223
      skaters who responded, 128 were male and 95 were female. Ages ranged from 12 to
      64 (mean, 29) yr. Some kind of injury was reported by 87 (39%) of the
      participants. The majority of those injuries occurred when the skaters were
      beginners (46). Skin abrasions and musculoligamentous injuries were the most
      common. Only 15 (17.2%) sought medical treatment, and of these, 5 were treated
      for fractures: 3 at the wrist and 1 each at the ankle and knee. The knee was the
      most commonly injured part of the body (24.7%), followed by the elbow and wrist.
      Approximately 5% of all injuries involved the head. Many skaters did not wear
      helmets or knee pads, even though they owned this equipment. There was a strong
      preference for wearing wrist pads, either alone or with other protective gear.
      This suggests that skaters have learned that the wrist is particularly vulnerable
      to serious injury and should be protected.

PMID- 9923423
TI  - Mylohyoid late responses elicited with intraoral stimulation.
AB  - Many disorders affect the trigeminal nerve, highlighting the need for
      electrodiagnostic methods to evaluate this cranial nerve. The purpose of this
      study was to develop and refine clinical nerve conduction techniques for
      examining mylohyoid late responses and to establish normative clinical data.
      Intraoral stimulation of the mylohyoid nerve was performed on normal volunteers
      using a pediatric stimulator taped to a tongue depressor. Mylohyoid direct and
      late responses were recorded with surface electrodes over the mylohyoid muscles.
      Mylohyoid late responses with supraorbital nerve stimulation and blink reflexes
      were also elicited. Fifty-four subjects, 65% females, with an average age of 39.2
      (standard deviation, 13.4) yr, were studied. Direct mylohyoid responses were
      elicited in all subjects with a mean of 1.8 (standard deviation, 0.3) ms and
      amplitude of 4.1 (standard deviation, 1.4) mV. Late responses occurred in 94%
      ipsilaterally at an average latency of 32.4 (standard deviation, 6.5) ms and in
      90% contralaterally at 32.4 (standard deviation, 5.6) ms. Two distinct late
      responses, the second occurring at an average of 72.3 (standard deviation, 12.4)
      ms with intraoral stimulation were noted in 25% of subjects. Only 11% of subjects
      had mylohyoid late responses with supraorbital stimulation. Blink (R1) reflexes
      occurred in 89% (10.9 ms; standard deviation, 0.7 ms), ipsilateral R2 responses
      in 88% (35.2 ms; standard deviation, 3.4 ms), and contralateral R2 responses in
      69% (36.2 ms; standard deviation, 4.0 ms). Mylohyoid late responses are present
      in most normal subjects. The neuroanatomical pathways mediating these responses
      require delineation. These nerve conduction techniques may be useful in
      evaluating patients with suspected trigeminal nerve disorders.

PMID- 9923424
TI  - Changes in the quality of life of hemiplegic stroke patients with time: a
      preliminary report.
AB  - To evaluate the influence of time on the quality of life of hemiplegic stroke
      patients living at home, we analyzed a sample of 45 outpatients. The sample was
      divided into two groups, according to the delay between the discharge time from
      hospital and the assessment (Group 1, fewer than 6 mo; Group 2, more than 6 mo
      after discharge). We hypothesized that patients in Group 2 would have a lower
      level of quality of life than patients in Group 1. Disability was assessed with
      the Functional Independence Measure, and the quality of life was assessed with
      the Reintegration to Normal Living Index. Both groups were comparable with regard
      to demographic and stroke characteristics. There was no statistically significant
      difference in Functional Independence Measure scores (global and subscales).
      Reintegration to Normal Living Index-perception of self subscale scores were
      significantly lower in Group 2. At the item level, quality of life scores were
      also significantly lower in Group 2 for indoor mobility (Mann-Whitney U test; P =
      0.001), self-care needs (P = 0.005), personal relationships (P = 0.02), and the
      handling of life events (P = 0.05). These results confirm our hypothesis and
      suggest that quality of life may deteriorate in some domains over time, even when
      the disability level is unchanged, but these results need to be replicated in
      prospective studies with larger samples of stroke survivors.

PMID- 9923425
TI  - Normal values for sensory thresholds in the cervical dermatomes: a critical note
      on the use of Semmes-Weinstein monofilaments.
AB  - In many healthy subjects, sensory thresholds for touch using Semmes-Weinstein
      monofilaments appear to be higher than the 2.83 filament, which some authors have
      suggested as a screening instrument. The currently proposed normal values, the
      interpretation of results, as well as the calibration of the filaments are
      questioned. A normative study of 20 normal subjects using Semmes-Weinstein
      monofilaments was undertaken at a pain clinic in a university hospital. The main
      outcome measures were sensory thresholds (touch) in dermatomes C3 to C8. Per
      subject, 24 sites were tested and 50 sites in dermatome C5 left of one subject.
      The threshold distribution patterns were analyzed. The mean threshold expressed
      in log (10 x F; with F = force in milligrams) of all sites (n = 480) in normal
      subjects was 3.10 (95% confidence interval, 2.34-3.86). The mean threshold per
      subject was 3.10 (range, 2.70-3.50). The mean threshold of 50 sites in dermatome
      C5 left of one healthy subject was 3.22 (range, 2.42-4.02). In the study
      contained herein, sensory thresholds in the cervical dermatomes have been shown
      to be higher than the generally proposed normal values. The cervical dermatomes
      show thresholds from 0.13 to 8.47 mN. This concurs with other authors. Results
      depend on the testing method, which in this study was different from previous
      studies. The testing method must be described accurately. The distribution of
      thresholds within all tested sites, dermatomes, subjects, or even within one
      dermatome in one subject are comparable. Individual results have to be related to
      the mean of the subject to determine abnormality. Calibration of the
      monofilaments is important. When these terms are met, testing with Semmes
      Weinstein monofilaments is an easy, reliable, and relatively inexpensive method
      of quantitative sensory testing and can be a useful tool in the process of
      rehabilitation.

PMID- 9923427
TI  - Cerebral autoregulation during whole-body hypothermia and hyperthermia stimulus.
AB  - The purpose of the study contained herein was to investigate the effects of old
      traditional physiotherapeutic treatments on cerebral autoregulation. Treatment
      consisted of complete body immersion in cold or warm water baths. Fifteen
      volunteers were investigated by means of transcranial Doppler sonography and a
      servo-controlled noninvasive device for blood pressure measuring. One group of 8
      volunteers (mean age, 27.2+/-3.5 yr; gender, 3 females/5 males) was subjected to
      cold baths of 22 degrees C for 20 min Another group of 7 volunteers (mean age,
      52.1+/-8.5 yr; gender, 4 females/3 males) took hyperthermic baths at rising water
      temperatures from 36 degrees to 42 degrees C, increased by 1 degree C every 5
      min. Each volunteer in both groups underwent autoregulation tests two to four
      times before, during, and after the thermic bath. Dynamic autoregulation was
      measured by the response of cerebral blood flow velocity to a transient decrease
      of the mean arterial blood pressure, induced by rapid deflation of thigh cuffs.
      The autoregulation index, i.e., a measure of the speed of change of cerebral
      autoregulation, was used to quantify the response. Further parameters were core
      temperature, blood pressure (mm Hg) and CO2et. During hypothermic baths, core
      temperature decreased by 0.3 degrees C (P = 0.001), measured between preliminary
      phase and the end of the bath; the autoregulation index decreased significantly
      (P < 0.05) from 5.3 before the bath to 4.25 during the bath. During hyperthermic
      baths, the autoregulation index increased from 6.0 to 7.5 and 8.9 (P < 0.001),
      with an increase of core temperature of 0.4 degrees C. The main cerebral
      autoregulation system is dependent on changes of core temperature, provoked by
      hypothermic or hyperthermic whole-body thermostimulus. Application of
      hyperthermic baths increased the autoregulation index, and hypothermic baths
      decreased the autoregulation index. Further studies are needed to prove the
      positive effects of thermo-stimulating water applications on cerebral
      hemodynamics in patients with cerebral diseases.

PMID- 9923426
TI  - Efficacy of home cervical traction therapy.
AB  - Cervical traction is administered by various techniques ranging from supine
      mechanical motorized cervical traction to seated cervical traction using an over
      the-door pulley support with attached weights. Duration of cervical traction can
      range from a few minutes to 20 to 30 min, once or twice weekly to several times
      per day. Anecdotal evidence suggests efficacy and safety, but there is no
      documentation of efficacy of cervical traction beyond short-term pain reduction.
      Because of a clinical impression that a simplified, inexpensive, over-the-door
      home cervical traction method of treatment requiring 5 min of cervical traction
      twice daily was efficacious for both cervical pain and radiculopathic syndromes,
      we undertook a retrospective study of 58 outpatients treated between 1994 and
      1996. Age range was 29 to 84 (mean, 56) yr. Twenty-three males and 35 females
      were classified as Grade 1 to Grade 3 according to the Quebec Task Force of
      Whiplash-Associated Disorders Cohort Study. Outcomes were as follows: Grade 1
      (mild)--4 of 4 (100%) patients improved; Grade 2 (moderate)--34 of 44 (77%)
      patients improved (P < 0.01), 5 were unchanged, and 5 felt their symptoms were
      aggravated by cervical traction; Grade 3 (patients with radiculopathy)--9 of 10
      (90%) patients improved (P < 0.01). In a retrospective study, a brief (3-5 min),
      over-the-door home cervical traction modality provided symptomatic relief in 81%
      of the patients with mild to moderately severe (Grade 3) cervical spondylosis
      syndromes. Prospective, randomized assessment of cervical traction for this and
      other methods is needed.

PMID- 9923428
TI  - Proprioceptive function in knees with and without total knee arthroplasty.
AB  - The goal of this study was to evaluate the differences in angle reproduction
      capability after nonconstrained posterior cruciate ligament retaining total knee
      arthroplasty after a follow-up time of 63.9 months compared with the healthy
      contralateral leg and a control group. In 28 total knee arthroplasty patients
      (mean age, 65.7 yr) and 25 control subjects (mean age, 55.7 yr), 16 measurements
      were made between 0 degrees and 90 degrees in 30 degree steps. The leg was
      positioned by the examiner and then relaxed; afterward, the subject was asked to
      reproduce the original position. Each measurement was made with the patient or
      control being blindfolded and not blindfolded to assess the influence of visual
      control. We found significant differences in total knee arthroplasty patients in
      contrast to healthy subjects. Without visual control, the mean deviation of the
      total knee arthroplasty group starting with a 0 degree angle was 7.7+/-5.9
      degrees and 4.6+/-4.7 degrees for the healthy subjects. With visual control, the
      mean deviation in the patient group was 11+/-7.5 degrees, and in the control
      group, it was 7.2+/-5.0 degrees. Total knee arthroplasty patients did not show
      significant differences between the operated on and the contralateral knee. Also,
      in the total knee arthroplasty group, significant differences could not be found
      comparing reproduction with and without visual control and comparing both
      starting positions. In the control group, significant differences could be found
      comparing visual and nonvisual control in the 60 degree angle. The comparison
      between the 30 and 60 degree repositioning from both 0 and 90 degree starting
      positions showed a significant difference in the 60 degree angle. In summary,
      reduced proprioceptive capabilities are present after knee arthroplasty in both
      the operated on and the contralateral leg in our study group. Postoperative
      complaints can perhaps be explained by a loss of proprioceptive capabilities,
      especially at the 60 degree angle. The operative technique should involve special
      care of ligaments and muscles to preserve stability and receptors as well.
      Rehabilitation should pay more attention to the remaining receptors.

PMID- 9923429
TI  - Comparison of sperm quantity and quality in antegrade V retrograde ejaculates
      obtained by vibratory penile stimulation in males with spinal cord injury.
AB  - Reduced fertility in men with spinal cord injury results from the inability to
      ejaculate and poor semen quality. Vibratory penile stimulation can induce
      ejaculation in many men with spinal cord injuries, but few studies have reported
      the effects of repeated vibratory stimulation on quantitative semen analysis
      tests. Fourteen spinal cord-injured males were enrolled in a prospective study to
      develop a quantitative profile of antegrade and retrograde ejaculate specimens
      collected during repeated vibratory stimulation. Antegrade specimens were
      obtained in 51 (84%) and retrograde specimens were obtained in all of the 61
      trials (100%). Sperm were present in 70% and 64% of the antegrade and retrograde
      samples, respectively. Of the patients who underwent repeated vibratory
      stimulation attempts, three showed marked improvement in sperm counts and
      characteristics with repeated vibration and five showed normal fluctuation or no
      change in semen quality. Overall, there was a trend toward higher sperm counts in
      the antegrade samples (mean, 74.1 million) than in the retrograde samples (mean,
      40 million), but no statistical significance was found. Mean sperm motility,
      sperm progressive motility, and percent normal sperm morphology were not
      significantly different between antegrade and retrograde specimens. Fructose and
      zinc, semen markers that reflect the presence of a true ejaculate, were present
      in all antegrade and retrograde specimens. In conclusion, (1) both antegrade and
      retrograde ejaculation occur with vibratory penile stimulation, with antegrade
      samples containing greater numbers of sperm but retrograde samples also having
      significant sperm counts, (2) repeated vibration may increase sperm concentration
      or may result in only minimal changes reflective of normal fluctuations, and (3)
      vibratory stimulation results in true ejaculation, as evidenced by semen markers.

PMID- 9923431
TI  - Morbidly obese patients with pulmonary disease--a retrospective study of four
      cases: a brief report.
AB  - Morbid obesity is a common chronic condition that predisposes affected
      individuals to a decrease in functional status. The purpose of this case series
      is to highlight the benefit of institutional rehabilitation for this subgroup of
      patients. A 6-mo retrospective review of 117 consecutive admissions to the
      rehabilitation unit of a municipal hospital center was conducted. A total of four
      patients (3.4%) met the criteria for morbid obesity. We present the brief case
      histories of these four subjects. All showed significant functional improvement
      and were able to return home after a mean length of stay of 61 days. They each
      required specialized rehabilitation intervention and specialized equipment such
      as extra large beds and oversize walkers. All four subjects had obstructive
      pulmonary disease, accounting for their initial hospital admission. This study
      demonstrates that inpatient rehabilitation improves functional status in morbidly
      obese patients. Further research regarding physiatric intervention in the
      morbidly obese patient is needed.

PMID- 9923432
TI  - Preserved motor evoked potentials fail to predict functional outcome in
      quadriplegia because of bilateral lesions of the supplementary motor areas: a
      brief report.
AB  - We present a patient with a lesion of the mesial frontal cortex, including the
      supplementary motor areas bilaterally, who on clinical examination revealed no
      spontaneous movements, although neurophysiological examination indicated
      integrity of the corticospinal tract to thenar and tibialis anterior muscles
      bilaterally. The patient was alert, speech was hesitant, and he was able to move
      his hands only on command. The role of the supplementary motor areas in planning,
      setting, and execution of skillful voluntary movements has been previously
      established by direct cortical electrical stimulation and studies of regional
      cerebral blood flow. The findings in our patient support the role of the
      supplementary motor areas in initiating movements. The presence of motor evoked
      potentials after acute insults to the brain is considered to be associated with a
      good functional outcome. This is in contrast to our patient who did not show
      improvement in motor performance, despite preserved motor evoked potentials.
      Hence, in the case of bilateral lesions to the supplementary motor areas sparing
      the corticospinal tract, the presence of motor evoked potentials may not predict
      functional recovery.

PMID- 9923430
TI  - Hemiplegia and contralateral upper limb claudication--a case of dual disability
      from pseudoaneurysm of the brachiocephalic artery: a brief report.
AB  - Thromboembolic obstruction of the brachiocephalic artery can have significant
      functional consequences because it threatens arterial circulation to the right
      upper limb and right cerebrum. A case is presented of a young man who sustained
      right basal ganglia infarct 2 mo after suffering multiple gunshot wounds to his
      chest. The severity of his hemiplegia rendered his left arm nonfunctional. Later,
      he developed progressive symptoms of right upper limb claudication, making it
      impossible to perform activities of daily living independently with the
      hemiplegic technique. Arteriography revealed a pseudoaneurysm near the
      bifurcation of the brachiocephalic artery; the likely source was thromboembolism
      to the right common carotid and right subclavian artery. Surgical ligation of the
      subclavian artery and vascular bypass from the common carotid to the brachial
      artery restored blood flow to his right upper limb. The arm claudication was
      relieved, and he was again able to perform activities of daily living
      independently. This case represents an unusual cause of dual disability with
      bilateral upper limb dysfunction from a single thromboembolic source. Accurate
      diagnosis and treatment prevented this patient from developing permanent
      impairment and restored him to functional independence.

PMID- 9923433
TI  - Varicosities of the paravertebral plexus of veins associated with nocturnal
      spinal pain as imaged by magnetic resonance venography: a brief report.

PMID- 9923434
TI  - Medical decision-making with persons who are minimally conscious: a commentary.

PMID- 9923436
TI  - Weaning from mechanical ventilation in a general rehabilitation center: a
      commentary.

PMID- 9923435
TI  - Denial of chronic pain--a disturbing new management paradigm: a commentary.

PMID- 9923437
TI  - Use of sequential medical trials in rehabilitation research.
AB  - Although randomized, clinical trial designs represent the pinnacle of research
      excellence, they are often difficult to implement in natural or clinical
      settings. An alternative approach to analysis of data collected during
      rehabilitation research is the sequential medical trial design. In a sequential
      medical trial, subjects are serially recruited and the results are continuously
      analyzed. The use of preconstructed sequential charts remove the need for
      clinicians to perform complicated statistical analyses and allow an immediate
      visual indication of the direction the results are taking. Benefits of sequential
      medical trials are as follows: as soon as enough data are collected to show
      treatment preference, the trial is stopped; a trial that is showing no beneficial
      or even harmful effects can be quickly terminated; fewer subjects are needed
      (without loss of statistical power); features such as randomization, blinding,
      and cross-over designs can be included; the design suits the serial nature of
      rehabilitation practice. Limitations to sequential medical trials are that in
      simple designs extraneous factors cannot be controlled for and that multiple
      dependent variables are difficult to assess. This article discusses the theory
      behind the sequential medical trial design and outlines how to plan a sequential
      medical trial, recruit subjects, construct and use a simple sequential chart, and
      analyze and interpret the results. Examples of sequential medical trials used in
      rehabilitation research are presented. It is hoped that this article will
      increase the exposure of this useful design and result in greater use of
      sequential medical trials by rehabilitation professionals.

PMID- 9923438
TI  - The Fanconi anemia group C gene product modulates apoptotic responses to tumor
      necrosis factor-alpha and Fas ligand but does not suppress expression of
      receptors of the tumor necrosis factor receptor superfamily.
AB  - Exposure of hematopoietic progenitor cells (HPC) from mice and humans with
      Fanconi anemia group C (FAC) to interferon-gamma (IFN-gamma) or tumor necrosis
      factor-alpha (TNF-alpha) at doses too low to inhibit growth of normal HPC induces
      profound apoptotic responses. Because the IFN-gamma hypersensitivity of cells
      lacking the FAC protein is mediated, in part, through priming of the Fas pathway,
      and because several other members of this family are capable of inducing
      apoptosis either alone or in concert with each other, we tested the hypothesis
      that IFN-gamma induces increased expression of members of the TNF receptor (TNFR)
      superfamily in cells nullizygous for the FAC gene. Using isogenic human Epstein
      Barr virus-transformed lymphoblast cell lines and c-kit+ bone marrow cells from
      mice with inactivating mutations of the FAC locus, we quantified mRNA levels by
      reverse transcriptase polymerase chain reaction and surface expression of the
      gene products by flow cytometry of TNFR1, TNFR2, Fas, CD30, CD40, and nerve
      growth factor receptor. We found that neither constitutive nor IFN-gamma-induced
      expression of these receptors was influenced by the absence of a functional FAC
      gene product, and expression of these receptors was not suppressed in nullizygous
      cells complemented with the normal FAC cDNA. We conclude that, although
      exaggerated apoptotic responses in FAC-deficient cells are at least partially
      mediated through activation of members of the TNFR superfamily, the normal FAC
      protein does not function as a direct suppressor of this family of molecules and
      inactivation of FAC does not augment expression of these proteins.

PMID- 9923440
TI  - Chronopharmacologic aspects of continuous AcSDKP infusion in mice.
AB  - Inconsistent results characterized N-acetyl-Ser-Asp-Lys-Pro (AcSDKP or
      Goralatide) effects upon hematologic proliferation, possibly because its
      circadian organization had been overlooked. We investigated the circadian changes
      in AcSDKP disposition in plasma and in bone marrow during continuous infusion and
      AcSDKP effects upon the circadian rhythms in bone marrow granulomonocytic
      precursors (CFU-GM) and circulating blood cell counts. One hundred ninety-six
      male B6D2F1 mice received a constant infusion of AcSDKP (24 microg/ day) or 0.9%
      NaCl for 7 days, using an osmotic minipump. All mice were synchronized with an
      alternation of 12 hours of light and 12 hours of darkness for 3 weeks prior to
      study. Mice were sacrificed on the fifth or seventh infusional day at 3, 9, 15,
      or 21 hours after light onset (HALO) in order to assess plasma and bone marrow
      AcSDKP concentrations, CFU-GM, and/or circulating blood cell counts. In control
      mice, plasma and bone marrow AcSDKP concentrations displayed a circadian rhythm
      with a maximum level during the dark span, at 21 and 15 HALO respectively, while
      CFU-GM, leukocyte, lymphocyte, and monocyte counts peaked during early light.
      Continuous AcSDKP infusion increased fivefold mean plasma AcSDKP level at 3 or 9
      HALO, thus inverted its physiologic rhythm and suppressed the CFU-GM peak that
      normally occurs at these times. This inhibition however, was indirect, because
      the rhythms in bone marrow AcSDKP concentration were similar with or without
      AcSDKP infusion. Conversely, mean leukocyte and lymphocyte counts were
      significantly reduced with AcSDKP infusion, while their circadian rhythms
      remained unaffected and were amplified. The results indicate that AcSDKP
      pharmacology displays circadian rhythmicity and warrant the exploration of
      chronopharmacologic schedules of AcSDKP delivery for further protecting bone
      marrow against chemotherapy insults.

PMID- 9923439
TI  - Long-term bone marrow cultures in Diamond-Blackfan anemia reveal a defect of both
      granulomacrophage and erythroid progenitors.
AB  - The hematopoietic defect of Diamond-Blackfan anemia (DBA) results in selective
      failure of erythropoiesis. Thus far, it is not known whether this defect
      originates from an intrinsic impediment of hematopoietic progenitors to move
      forward along the erythroid pathway or to the impaired capacity of the bone
      marrow (BM) microenvironment to support proliferation and differentiation of
      hematopoietic cells. Reduced longevity of long-term bone marrow cultures, the
      most physiologic in vitro system to study the interactions of hematopoietic
      progenitors and hematopoietic microenvironment, is consistent with a defect of an
      early hematopoietic progenitor in DBA. However, stromal adherent layers from DBA
      patients generated in a long-term culture system, the in vitro counterpart of BM
      microenvironment, did not show evidence of any morphologic, phenotypic, or
      functional abnormality. Our major finding was an impaired capacity of enriched
      CD34+ BM cell fraction from DBA patients, cultured in the presence of normal BM
      stromal cells, to proliferate and differentiate along the erythroid pathway. A
      similar impairment was observed in some DBA patients along the granulomacrophage
      pathway. Our result points to an intrinsic defect of a hematopoietic progenitor
      with bilineage potential that is earlier than previously suspected as a relevant
      pathogenetic mechanism of the disease. The finding of impaired granulopoiesis in
      some DBA patients underlines the heterogeneity of this rare disorder.

PMID- 9923441
TI  - Interleukin-8: an autocrine/paracrine growth factor for human hematopoietic
      progenitors acting in synergy with colony stimulating factor-1 to promote
      monocyte-macrophage growth and differentiation.
AB  - We previously reported that alteration of the function of heterotrimeric Gi2
      proteins altered proliferation of murine macrophages in response to colony
      stimulating factor-1 (CSF-1). Here we show that a Gi2 agonist, C-X-C chemokine
      interleukin-8 (IL-8), regulates monocyte-macrophage growth and differentiation.
      In the absence of serum, IL-8 (10 ng/mL) synergized with CSF-1 to stimulate
      murine monocyte-macrophage proliferation, enhanced proliferation of purified
      human CD34+ cells and increased the number and size of CSF-1-induced monocyte
      macrophage colonies formed by purified CD34+ cells in semisolid medium. Next, as
      both CD34+ cells and monocyte-macrophages can produce IL-8, we used an anti-human
      IL-8 antibody to block an eventual activation of IL-8 receptors by autocrine IL
      8. Preincubation with anti-human IL-8 antibody (20-40 microg/mL) inhibited the
      proliferation as well as the monocyte-macrophage colony clonogenicity of purified
      human CD34+ cells. Hence, in addition to being a powerful neutrophil
      chemoattractant, IL-8 also acts as an autocrine/paracrine growth factor for human
      hematopoietic progenitors, promoting the growth and differentiation of cells of
      monocytic lineage.

PMID- 9923442
TI  - Analysis of erythropoietin and erythropoietin receptor genes expression in cattle
      during acute infection with Trypanosoma congolense.
AB  - Acute Trypanosoma congolense infection induced moderate, transient anemia in
      N'Dama cattle (trypanotolerant) and severe anemia in Boran cattle
      (trypanosusceptible). Erythropoietin receptor (EpoR) was cloned and sequenced
      from the two breeds of cattle. A single position mutation of Tyr in the Boran to
      His in the N'Dama predicted amino acid sequence was revealed. The mRNA
      transcription of erythropoietin (Epo) in kidneys and EpoR in the bone marrow of
      infected cattle was determined by competitive reverse transcription and the
      polymerase chain reaction (RT-PCR). Though Epo mRNA transcription increased in
      the kidneys during infection, the increase was not significantly different
      (p>0.05) between the two breeds of infected cattle. The level of EpoR transcripts
      in the bone marrow of infected N'Damas was significantly higher (p<0.05) than
      that detected in the marrows from infected Boran cattle. While infection seem to
      increase levels of transcription of IL-1alpha and beta, and TNFalpha in kidneys
      from both Boran and N'Dama cattle, no significant difference was detected in the
      level of mRNAs of these cytokines in the kidney from the two breed of cattle. The
      amount of IFNgamma mRNA transcripts were not changed with infection in N'Dama
      cattle, while on the contrary a significant higher levels of IFNgamma was found
      in kidneys from infected Boran cattle as compared to the other groups. A
      significant (p<0.05) increase in the levels of IL-1alpha and beta, and IFNgamma
      mRNA transcripts were detected in the marrows of infected Borans as compared to
      the infected N'Dama cattle. In this study the increase in the level of TNFalpha
      mRNA in the marrows of the two infected breeds was not different. This implies
      there is no negative effect of TNFalpha on hematopoiesis during acute infection.
      These findings suggest that the levels of Epo and EpoR in the infected Boran
      cattle were inadequate for their degree of anemia, which might be due in part to
      high expression of IFNgamma during acute infection with T. congolense.

PMID- 9923443
TI  - Maturation and developmental stage-related changes in fetal globin gene
      expression are reproduced in transiently transfected primary adult human
      erythroblasts.
AB  - A novel system is described, which uses transfection of primary human
      erythroblasts for the study of gene regulation in differentiating human red
      cells. This system includes a protocol for liquid culture of erythroid
      progenitors, which reproduces developmental differences in globin gene expression
      found between adult and cord blood as well as the maturation-related changes in
      fetal globin levels observed in adult cells. Reporter constructs driven by globin
      gene promoters were electroporated into adult and cord blood-derived
      erythroblasts at different time points during culture. Both the developmental
      stage and maturation-related differences in endogenous fetal and adult globin
      gene expression could be reproduced by the transiently transfected reporter
      constructs. Transfection of primary human erythroblasts during differentiation
      provides a previously unavailable opportunity to study dynamic aspects of
      erythropoiesis.

PMID- 9923444
TI  - Late expression of red cell membrane protein 4.2 in normal human erythroid
      maturation with seven isoforms of the protein 4.2 gene.
AB  - The expression of protein 4.2 in normal human erythroid cells was studied
      utilizing erythroblasts from bone marrow and erythroid cells cultured by the two
      phase liquid culture method from burst-forming unit erythroid (BFU-E) in
      peripheral blood. As opposed to spectrin, which was expressed in erythroid
      progenitors or very early erythroblasts, protein 4.2 was first detected in late
      erythroblasts with a morphology nearly identical to orthochromatic erythroblasts.
      Among the various major membrane proteins, the expression of protein 4.2 was the
      latest. At the gene level, protein 4.2 gene mRNA was expressed in early
      erythroblasts. During normal erythroid maturation, the expression of seven
      different protein 4.2 gene products was observed by Southern blot analysis. These
      seven gene products appeared to be derived from protein 4.2 gene in the presence
      or absence of skipping of the 90 bp in exon 1, exon 3, and/or exon 5, as judged
      by deduction from the protein 4.2 sequence. Therefore, it can be speculated that
      protein 4.2 is expressed after the cytoskeletal network has been constructed and
      assembled with integral proteins in the membrane lipid bilayer.

PMID- 9923446
TI  - Retroviral transduction of enriched hematopoietic stem cells allows lifelong Bcl
      2 expression in multiple lineages but does not perturb hematopoiesis.
AB  - Transduction of hematopoietic stem cells with a novel retrovirus has allowed long
      term expression of human Bcl-2 in multiple hematopoietic lineages. Thy-1.2lo Sca
      1+ H-2Khi stem cells enriched from the bone marrow of 5-fluorouracil-treated (Ly5
      2) mice were infected with the bcl-2 retrovirus and injected into (Ly5-1)
      irradiated recipients. Analysis at 5 months indicated that reconstitution of
      hematopoiesis occurred predominantly from donor-derived (Ly5-2+) stem cells and
      that, in half the mice (18 of 35), most blood cells derived from virally
      transduced stem cells. The level of Bcl-2 expression achieved with the retroviral
      vector approached that of a well-characterized transgenic vector and could be
      sustained for life in several blood cell lineages. In the 25 mice assessed at 10
      months, human Bcl-2 was readily detectable in 62+/-22% of Ly5-2+ peripheral blood
      leukocytes. More detailed analysis of a cohort killed between 14 and 20 months
      established that human Bcl-2 protein could be detected in B and T lymphocytes,
      granulocytes, macrophages, and some immature erythroid cells. Furthermore,
      hematopoietic stem cells from the bone marrow of these mice maintained Bcl-2
      expression in hematopoietic tissues of secondary recipients for at least another
      19 months. These data provide clear evidence for efficient infection of primitive
      hematopoietic stem cells and for maintenance of proviral expression for over 2.5
      years, the lifespan of mice. The level of exogenous Bcl-2 was sufficient to
      enhance survival of B and T lymphoid cells, granulocytes, and myeloid colony
      forming cells cultured under suboptimal conditions, but hematopoiesis in the mice
      was not notably perturbed.

PMID- 9923445
TI  - A human erythropoietin receptor gene mutant causing familial erythrocytosis is
      associated with deregulation of the rates of Jak2 and Stat5 inactivation.
AB  - The erythropoietin receptor (EpoR) has been previously shown to contain a
      cytoplasmic C-terminal negative regulatory domain, experimental deletion or
      mutation of which leads to increased sensitivity of expressing cells to the
      effects erythropoietin (Epo). We have studied a naturally occurring C-terminal
      truncation mutant of the human EpoR by stably transfecting the growth factor
      dependent hematopoietic tissue culture cell line 32D with expression plasmids
      containing either the wildtype or mutant human EpoR cDNA, thus rendering the
      cells dependent on Epo for viability and proliferation. In Epo dose-response
      assays, cells expressing the mutant EpoR displayed hyperresponsiveness to Epo
      compared with cells expressing comparable numbers of the wild-type EpoR cultured
      in the presence of fetal bovine serum. We investigated whether enhanced Epo
      sensitivity of cells expressing the truncated EpoR is associated with alteration
      in Epo receptor-mediated activation of Stat5, which could have a role in Epo
      induced proliferation. Although maximal Stat5 activation in response to a given
      concentration of Epo was comparable in 32D cells expressing the wild-type or
      truncated EpoRs, the time course of Epo-induced Stat5 activation was very
      different. Gel-mobility shift studies revealed the presence of Stat5 DNA-binding
      activity in nuclear and cytoplasmic extracts of cells expressing the truncated
      EpoR for a significantly longer time than that observed in similar extracts of
      cells expressing the wild-type EpoR consistent with decreased rate of
      inactivation of Stat5 in cells expressing the mutant EpoR. Epo-dependent tyrosine
      phosphorylation of both Stat5 and Jak2 was also substantially prolonged in cells
      expressing the truncated EpoR. These results suggest a role for Stat5 in
      regulation of Epo-mediated cell growth and implicate altered kinetics of Epo
      induced Jak2 and Stat5 activation in the pathogenesis of familial erythrocytosis
      associated with this naturally occurring EpoR gene mutation.

PMID- 9923447
TI  - A novel growth-factor-dependent myeloid cell line derived from mouse bone marrow
      cells contains progenitors endowed with high proliferative potential.
AB  - Constitutive expression of human colony-stimulating factor-1 receptor (CSF-1R)
      confers long-lasting CSF-1-dependent proliferation to mouse myeloid cell lines.
      We developed mice transgenic for human CSF-1R because mouse CSF-1 cannot activate
      human CSF-1R. Then bone marrow cells from transgenic mice were plated onto MS-5
      stromal cells expressing the membrane form of human CSF-1 (2M-1 cells) in order
      to combine the hematopoietic supporting properties of stromal cells and the
      proliferative effects of CSF-1. Thus, we were able to derive a hematopoietic cell
      line, called 47.10, that grew indefinitely under these conditions, whereas no
      cell line could be developed from nontransgenic mice. Proliferation of 47.10
      cells is severely affected by neutralizing anti-CSF-1R monoclonal antibodies.
      Morphologic and cytofluorometry analysis established that most 47.10 cells are
      immature myelomonocytic cells. Consistent with this phenotype, the myeloid
      transcription factor PU.1, but not the erythroid transcription factor GATA-1, is
      expressed in 47.10 cells. A few 47.10 cells (3-5%) do not express lineage
      specific markers; they differentiate spontaneously to lineage-positive cells
      after replating on 2M-1 cells. In agar cultures, 47.10 cells form 7- and 14-day
      colonies in response to a cocktail of granulocyte/macrophage colony-stimulating
      factor (2.5 ng/mL), interleukin-3 (1 ng/mL), and mouse CSF-1 (10 ng/mL). Under
      these conditions, about 0.5% of 47.10 cells formed large 14-day colonies (>1 mm)
      composed of mature monocytes and granulocytes, reflecting the presence of
      progenitors endowed with high proliferative potential (HPP-47.10 cells). In
      conclusion, we have characterized a novel continuous myeloid cell line presenting
      a hierarchical structure similar to that of the bone marrow progenitor cell
      compartment.

PMID- 9923448
TI  - Selectively induced high MRP gene expression in multidrug-resistant human HL60
      leukemia cells.
AB  - A subclone HL60/DOX was selected from a human leukemic HL60 cell line for
      resistance to doxorubicin (DOX) by exposure to stepwise increasing concentrations
      of the drug and coexposure to a potential P-glycoprotein (P-gp) inhibitor,
      cepharanthine (a biscoclaurine alkaloid). Compared with the parent HL60 cells,
      the HL60/DOX cells were 13.0-fold more resistant to DOX and showed multidrug
      resistant (MDR) phenotype characterized by 4.6-fold, 2.3-fold, and 5.7-fold cross
      resistance to vincristine, pirarubicin, and etoposide, respectively, but no cross
      resistance to alkylating agent, cisplatin. Immunocytochemical analyses using the
      specific monoclonal antibody, MRPr1, and quantitative analyses using a
      competitive reverse transcription-polymerase chain reaction (CRT-PCR) confirmed
      overexpression of MRP gene products (about 8-fold determined by CRT-PCR) in this
      resistant clone. The P-gp expression was not detectable by the monoclonal
      antibody, C219, in the HL60/DOX cells, and that was consistent with extremely low
      levels of mdr1 mRNA expression determined by CRT-PCR in this clone. Drug
      accumulation and efflux studies demonstrated the significantly increased efflux
      rate of DOX compared to the parent HL60 cells. This enhancement of DOX efflux was
      reversed by the addition of 10 microM verapamil. To investigate the additional
      underlying mechanisms contributing to MDR phenotype in the HL60/DOX cells, the
      levels of DNA topoisomerases (Topo) including Topo I, Topo IIalpha, and Topo
      IIbeta, and gamma-glutamylcystein synthetase (y-GCS) expression were determined
      using CRT-PCR techniques. Normal expression of each enzyme at the transcriptional
      level was demonstrated in this resistant clone. Southern blot analysis of the
      gene organization in the HL60/DOX cells revealed the amplification of MRP gene.
      These results indicate that alteration of the drug accumulation from enhanced
      efflux appears to be a major mechanism(s) of MDR phenotype and attributable to
      high levels of MRP expression in the HL60/DOX cells. Overexpression of MRP in
      this clone is regulated by the genomic amplification of DNA and increased levels
      of the MRP mRNA, independently with the normal expression of Topo I, Topo
      IIalpha, Topo IIbeta, or gamma-GCS.

PMID- 9923449
TI  - Expression of a foreign protein in human megakaryocytes and platelets by
      retrovirally mediated gene transfer.
AB  - Recent progress in the culture of human megakaryocytes (MKs) has led to the
      capacity to produce platelets in vitro. This capability enables investigation
      into the possibility of modifying platelet structure and/or function by
      genetically altering the MK. To this end, a cDNA for the murine CD9 (mCD9) cell
      surface protein was introduced into MK progenitors by retrovirally mediated gene
      transfer and subsequently detected in cultured MKs with a monoclonal antibody
      (MoAb) that specifically recognizes the murine protein. CD34+ human peripheral
      blood or marrow progenitors, enriched by immunomagnetic bead selection, were
      cultured for 5 days in the presence of growth factors, including stem cell factor
      and thrombopoietin, to induce MK progenitors into the cell cycle. The stimulated
      cells were then cocultured with the mCD9 retroviral producer cell line for 3
      days, followed by culture in serum-depleted medium for 3 to 7 additional days.
      Flow cytometry analysis using the anti-CD9 MoAb and TAB, a MoAb recognizing human
      GPIIb, revealed that a large proportion (40-100%) of the MKs expressed mCD9. To
      ascertain whether these cells were capable of producing mCD9+ platelets, flow
      cytometry analysis was performed at a time when proplatelets were observed in the
      culture. mCD9 was detected in up to 59% of the TAB+ platelet-sized particles.
      Because deteriorating MKs can produce platelet-sized particles in vitro,
      experiments were performed to determine whether mCD9+ TAB+ particles were
      functionally active. Addition of phorbol myristate acetate resulted in the
      redistribution of P-selectin (CD62) from the alpha granule to the platelet
      surface as detected by MoAbs S12 and G5 in three-color flow cytometry analyses.
      These studies showed that up to 76% of the mCD9+ TAB+ particles were functionally
      active. The data show that retrovirally mediated gene transfer is a viable
      approach for genetically altering MK progenitors, resulting in platelets that
      express heterologous proteins.

PMID- 9923451
TI  - Immature megakaryocytes undergo apoptosis in the absence of thrombopoietin.
AB  - We examined withdrawal effects of recombinant mouse Tpo (rm-Tpo) on the apoptosis
      of mature and immature megakaryocytes in in vitro experiments. Apoptotic
      megakaryocytes were detected by double staining for acetylcholinesterase and by
      the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. When the purified
      mature megakaryocytes were cultured with or without rm-Tpo, the numbers of viable
      megakaryocytes, apoptotic megakaryocytes, and megakaryocytes with cytoplasmic
      processes were not significantly different between the two groups. In contrast,
      purified immature megakaryocytes underwent apoptosis when rm-Tpo was absent from
      the culture system. Murine bone marrow cells were cultured with rm-Tpo (50 U/mL)
      on days 1-7 to generate immature megakaryocytes and subsequently were cultured
      with different concentrations of rm-Tpo (0-50 U/mL) on days 8-14. The number of
      viable megakaryocytes was decreased and that of apoptotic megakaryocytes was
      increased by rm-Tpo in a dose-dependent manner. These results indicated a clear
      relation between the rm-Tpo level and the apoptosis of immature megakaryocytes.

PMID- 9923450
TI  - The prolonged hematologic effects of a single injection of PEG-rHuMGDF in normal
      and thrombocytopenic mice.
AB  - A single injection of > or =10 microg/kg PEG-rHuMGDF in mice causes a dose
      dependent increase in circulating platelets beginning on day 3 and peaking on
      days 5-6. The mean platelet volume and platelet distribution width at doses > or
      =100 microg/kg initially increase in a dose-dependent fashion and later decrease.
      However, the mean platelet volume does not change when platelets are incubated
      with PEG-rHuMGDF in vitro. The number of marrow megakaryocytes increases in a
      dose-dependent fashion as early as day 1 and peaks on day 3. Marrow megakaryocyte
      colony-forming units (CFU-Meg) do not increase on days 1-3 at a dose of 100
      microg/kg (a dose that increases platelet numbers two- to threefold and may be
      clinically relevant), but the relative frequency of high ploidy megakaryocytes
      and the proportion of large marrow megakaryocytes (29-50 microm in diameter)
      increases. After a dose of 1,000 microg/kg the percentage of megakaryocytes in
      mitosis peaks at 24-48 hours and the percentage of megakaryocytes incorporating
      BrdU is maximal at 48 hours, the relatively delayed peak of BrdU incorporation
      most likely representing endomitosis. The relative frequency of type II and III
      megakaryocytes peaks on days 3 and 4, respectively. Pharmacokinetic analysis of
      PEG-rHuMGDF shows peak serum concentrations at 2-4 hours and a terminal half-life
      of 11.4+/-2.5 hours. A single injection of PEG-rHuMGDF ameliorates carboplatin
      induced megakaryocytopenia and thrombocytopenia in a dose-response dependent
      fashion. In conclusion, a single injection of PEG-rHuMGDF increases megakaryocyte
      and platelet production in normal and myelo-suppressed mice.

PMID- 9923452
TI  - Distinct actions of interleukin-9 and interleukin-4 on a hematopoietic stem cell
      line, EMLC1.
AB  - EMLC1 is a hematopoietic stem cell line that depends on stem cell factor (SCF)
      for growth and generates lymphoid, erythroid and myeloid progenitors in the
      presence of different cytokines. We have studied signaling events leading to cell
      proliferation and differentiation of EMLC1 mediated by interleukin (IL)-4 and IL
      9. It was found that IL-9 enhances SCF-induced cell proliferation and promotes
      erythropoietin (EPO)-dependent erythroid differentiation of EMLC1 cells. However,
      IL-9 alone cannot support the growth of this cell line. In contrast, IL-4 by
      itself is sufficient to promote the growth of EMLC1 cells, even in the absence of
      SCF. Antiphosphotyrosine immunoblots of total cell lysates demonstrated that IL-4
      and IL-9 induce tyrosine phosphorylation of different cellular substrates. Both
      IL-4 and IL-9 stimulated tyrosine phosphorylation of SHP-2, whereas the 90-kD
      tyrosine phosphorylated protein induced by IL-9 stimulation is Stat3. We have
      also shown that IL-4 is much more potent than IL-9 in inducing the expression of
      primary response gene c-myc. It was further determined that c-myc antisense
      oligodeoxynucleotide blocked IL-4 supported cell growth. Taken together, these
      results indicate that IL-4 may serve as a growth-promoting factor for
      hematopoietic stem cells, and IL-9 enhances both growth and erythroid
      differentiation of primitive hematopoietic progenitors. The results also suggest
      that differences in tyrosine phosphorylation induced by IL-4 and IL-9 may in part
      determine their distinct biological functions.

PMID- 9923453
TI  - Mobilization of peripheral blood progenitor cells for human immunodeficiency
      virus-infected individuals.
AB  - Gene therapy is becoming one of the most promising modalities for the treatment
      of acquired immunodeficiency syndrome. The purpose of this study was to
      investigate the mobilization and collection of peripheral blood progenitor cells
      from human immunodeficiency virus (HIV)-infected individuals using granulocyte
      colony-stimulating factor (G-CSF). A total of 10 patients (9 male, 1 female;
      median age 36.5 years) with varying circulating CD4+ cell counts (13.9
      1467/microL) were administered 10 microg/kg G-CSF daily for 6 days. Peripheral
      white blood cells (WBCs), CD34+ cell counts, lymphocyte subsets, and plasma
      viremia were monitored before each G-CSF injection. An average sixfold increase
      in WBCs was observed, which stabilized on day 4 or thereafter. The level of CD34+
      cells was increased by 20-fold, and did not differ between days 5 and 6. Smaller
      increases in CD4+, CD8+, and CD4+CD8+ cells were observed. HIV viral load, as
      measured by RNA copy number in plasma, was not significantly altered by G-CSF
      administration. The leukapheresis product (LP), collected on day 7, contained an
      average of 6.25+/-4.52 (mean +/- standard deviation) x 10(10) WBCs and 3.08+/
      2.98 x 10(6) CD34+ cells/kg. The levels of different CD34+ cell subsets were
      similar to those in the LPs of G-CSF-mobilized healthy individuals from an
      earlier study. Primitive hematopoietic cells (CD38- and CD38-HLA-DR+ cells) were
      detected in LPs (1.19+/-0.46% and 0.87+/-0.23%, respectively, of CD34+ cells).
      All parameters (WBC counts, lymphocyte populations, CD34+ cells, and HIV-1 RNA
      copies) measured 3 weeks after leukapheresis returned to baseline values. The
      administration of G-CSF was well tolerated by the HIV patients; side effects
      included bone pain, headache, flulike symptoms, and fatigue. There were no
      correlations between baseline CD4+ cell count and the WBCs, mononuclear cells, or
      CD34+ cells collected in the LP. Similarly, no correlation existed between
      baseline CD4+ and CD34+ cells, peak CD34+ cells, or days to achieve peak CD34+
      cell counts after G-CSF mobilization. Our results showed that: (1) maximal
      mobilization can be achieved after 4 days of G-CSF administration; (2)
      therapeutic quantities of hematopoietic cells can be collected and used for gene
      therapy; and (3) G-CSF administration is well tolerated and does not cause a
      clinically significant increase in viremia.

PMID- 9923454
TI  - Synergy of growth factors during mobilization of peripheral blood precursor cells
      with recombinant human Flt3-ligand and granulocyte colony-stimulating factor in
      rabbits.
AB  - The potential of recombinant human (rh)Flt3 ligand (FL), alone or in combination
      with other recombinant growth factors, to mobilize peripheral blood precursor
      cells (PBPCs) was examined in an animal model. Adult outbred New Zealand White
      rabbits received subcutaneous injections daily for 14 days in a standardized
      protocol; whole blood cell counts and colony-forming unit-granulocyte/macrophage
      (CFU-GM) colonies were measured 3 times weekly during the injection period and
      for an additional observation period of 14 days. Two animals in each group were
      treated as follows: 200 or 500 microg/kg FL, 10 microg/kg granulocyte colony
      stimulating factor (G-CSF), 10 or 75 microg/kg stem cell factor (SCF), 10
      microg/kg G-CSF + 500 microg/kg FL, 10 microg/kg G-CSF + 75 microg/kg SCF + 500
      microg/kg FL. Both G-CSF and FL induced a sustained and dose-dependent increase
      in the leukocyte count to a maximum of 5-fold. They were additive in combination,
      leading to a tenfold increase in white blood cell counts. No consistent pattern
      was observed for platelet counts or red blood cells. No toxic side effects were
      seen. Both G-CSF and FL mobilized CFU-GM in a dose-dependent fashion to a 59-fold
      increase for G-CSF and 116-fold for FL. Maximum mobilization occurred on day 4
      with G-CSF and on day 11 with FL. G-CSF + FL in combination acted
      synergistically, inducing a 503-fold increase of CFU-GM over baseline. The
      addition of SCF to this combination did not alter leukocyte counts or CFU-GM
      mobilization. Our results indicate that FL is a potent and safe agent for the
      mobilization of PB-PCs and is synergistic with G-CSF.

PMID- 9923455
TI  - The hemoglobin-deficit mouse: cure of the anemia following bone marrow
      transplantation with normal marrow.
AB  - The hemoglobin-deficit mouse mutant (hbd) is characterized by a severe microcytic
      anemia that is inherited in an autosomal-recessive manner. Previous results from
      our laboratory indicated that normal mice develop anemia if they are transplanted
      with bone marrow from mutant animals. Furthermore, we demonstrated a delay in
      erythroid reconstitution from hbd marrow compared to normal marrow. Although
      these experiments show a defect that is intrinsic to hbd marrow, it is unclear if
      the hbd phenotype is solely the result of a bone marrow-derived defect. To
      exclude an environmental influence on hbd anemia, we attempted to cure the defect
      by transplanting normal marrow into the hbd mouse. We observed that the
      transplanted animals converted to a normal phenotype. These results indicated
      that the defect is bone marrow derived. In contrast to the microcytosis mutant
      whose defective gene is ubiquitously expressed, our data suggest that the
      defective gene product is specific to hematopoietic cells.

PMID- 9923456
TI  - Combined positive/negative purging and transplantation of peripheral blood
      progenitor cell autografts in breast cancer patients: a pilot study.
AB  - This trial studied the feasibility and efficiency of a novel procedure of double
      purging to eliminate tumor cells from leukapheresis products of stage IV breast
      cancer patients. After induction and mobilization therapy, 35 leukapheresis
      products from 16 breast cancer patients were subjected to CD34+ enrichment (i.e.,
      positive selection) with the Isolex 300 device and subsequent immunomagnetic
      depletion of tumor cells (i.e., negative selection) using a cocktail of three
      monoclonal antibodies directed against epithelial antigens. Patients with
      clinical response to induction chemotherapy proceeded to tandem high-dose
      chemotherapy, which consisted of melphalan (140 mg/m2) followed by retransfusion
      of the purged graft. After hematologic recovery, patients received ifosfamide 14
      g/m2, carboplatin 1.5 g/m2, and etoposide 1.5g/m2 (ICE), again followed by
      autografting. After positive selection, a median purity of 96.6% CD34+ cells
      (range 48.4-99.2%) and a recovery of 56.8% (range 25.8-92.6%) were achieved.
      Subsequent negative purging resulted in a median CD34+ purity of 97.2%. Overall
      CD34+ recovery after both purging procedures was 51.1% (range 18.5-82.4%). Tumor
      cells were detectable in 8 of 16 (50%) starting fractions before purging. After
      both purging cycles, only 1 of 16 autografts remained positive for tumor cells
      compared to 3 of 16 after CD34+ selection. A calculated purging efficiency of 2
      to >4 log was achieved. Engraftment was rapid, reaching > or =500/microL
      neutrophils on day +10 after melphalan and on day +9 after ICE. A platelet count
      of > or =20.000/microL was reached on day +12 after melphalan and on day +11
      after ICE. Thus, combining positive and negative purging is feasible, further
      enhances purging efficiency, and does not compromise the quality of the graft,
      leading to rapid engraftment after high-dose chemotherapy.

PMID- 9923457
TI  - Endogenous hematopoietic reconstitution induced by human umbilical cord blood
      cells in immunocompromised mice: implications for adoptive therapy.
AB  - Human umbilical cord blood (HUCB) cells show promising advantages over bone
      marrow (BM) cells for a variety of diseases that require transplantation. We
      observed that lethally irradiated SJL/J mice given a single injection of HUCB
      cells survive, whereas vehicle-injected mice do not. Because survival is not due
      to long-term engraftment of HUCB cells, we used this HUCB/mouse model to
      investigate additional therapeutic benefits of HUCB cells. We investigated the
      mechanism by which HUCB cells accelerated endogenous hematopoiesis in mice that
      received either lethal (9.5 Gy) or lower-dose (8.0 Gy) radiation and then were
      given a single injection of HUCB mononuclear cells. Compared to irradiated
      control mice, the lethally irradiated, HUCB-injected group showed significant
      increases in peripheral white blood cell counts, red blood cell indices, and
      granulocyte-macrophage colony-forming units (CFU-GM) by 3 weeks. In contrast, no
      significant differences in these parameters were observed between control and
      HUCB-injected mice that received the lower dose of irradiation. Moreover,
      regardless of the radiation dose, only HUCB-injected mice exhibited immune
      responses comparable to those of age-matched normal mice. The clinical relevance
      of these observations was determined in long-term, culture-initiating cell assays
      with human BM stem cells and irradiated (gamma-) HUCB cells. CFU-GM colonies were
      detectable in cultures containing gamma-HUCB cells by day 15, but were
      undetectable in cultures without gamma-HUCB cells until day 40, suggesting a
      hematopoietic stimulatory role for HUCB cells. Overall, the results indicate that
      in addition to their use for transplantation, HUCB cells also may be used as an
      adjuvant therapy to enhance hematopoietic reconstitution and immunocompetence of
      the host. This hematopoiesis-enhancing effect represents a heretofore
      unrecognized function of HUCB cells.

PMID- 9923458
TI  - A local renin--angiotensin system in the bone marrow: hypothesis and clues.

PMID- 9923459
TI  - The best model of a cat is a cat, especially the same cat.

PMID- 9923460
TI  - Quick, automatic, and general activation of orthographic and phonological
      representations in young readers.
AB  - Second through 6th graders were presented with nonword primes (orthographic,
      pseudohomophone, and control) and target words displayed for durations (30 and 60
      ms) that were brief enough to prevent complete processing. Word reading skills
      were assessed by 3 word and nonword naming tasks. Good readers exhibited more
      orthographic priming than poor readers at both durations and more pseudohomophone
      priming at the short duration only. This suggests that good readers activate
      letter and phonemic information more efficiently than poor readers. Good readers
      also exhibited an equal amount of priming at both durations, whereas poor readers
      showed greater priming at the longer duration. This suggests that activation was
      not under strategic control. Finally, priming was reliable for both high- and low
      frequency targets. This suggests that readers activate consistent information
      regardless of target word characteristics. Thus, quick, automatic, and general
      activation of orthographic and phonological information in skilled readers
      results from the precision and redundancy of their lexical representations.

PMID- 9923461
TI  - Quality of adult book reading affects children's emergent literacy.
AB  - The authors assessed the relative benefits of 3 styles of adult book reading for
      preschoolers' emergent literacy. A describer style focused on describing pictures
      during the reading, a comprehender style focused on story meaning, and a
      performance-oriented style introduced the book and discussed story meaning on
      completion. Forty-eight 4-year-olds were randomly assigned to receive 1 of the 3
      reading styles over a 6-week period. Pretests and posttests measured children's
      receptive vocabulary, print, and story comprehension skills. A describer style of
      reading resulted in the greatest overall benefits for children's vocabulary and
      print skills, but a performance-oriented style was also beneficial when
      children's initial skill levels were taken into account. Future book-reading
      interventions should be tailored to children's initial skill levels.

PMID- 9923462
TI  - Young children learn to produce passives with nonce verbs.
AB  - Younger and older children (mean ages = 2 years 11 months and 3 years 5 months)
      learned 2 nonce verbs in a full passive or active transitive construction. When
      asked patient-focused questions encouraging passive-voice replies (e.g., "What
      happened to the ball?") or agent-focused questions encouraging active-voice
      replies (e.g., "What did Elmo do?"), children used a variety of strategies to
      meet the demands of the questions, usually without changing the construction in
      which the verb occurred. In Study 2 in which passive and active constructions
      were primed, 40% of the almost 3-year-old children used an active-introduced verb
      in a passive construction and 35% used a passive-introduced verb in an active
      transitive construction when discourse demands encouraged them to do so. Thus,
      before their 3rd birthdays, some children have an understanding of the passive
      and active transitive constructions general enough to support productive usages
      with newly learned verbs.

PMID- 9923463
TI  - Effects of prosodic stress and serial position on syllable omission in first
      words.
AB  - The authors documented syllable omission in one child's multisyllabic vocabulary
      from 10 to 20 months of age to evaluate L. Gerken's (1991, 1994a, 1994b) proposal
      that children organize their productions according to a trochaic metrical (strong
      weak) template and omit syllables from target utterances that do not conform to
      this pattern. The trochaic template hypothesis was not supported by these early
      productions. Results indicated that the likelihood of producing a target syllable
      was influenced primarily by the strength of the prosodic stress placed on it and
      secondarily by its serial order within a word. Over time, the child demonstrated
      an increasing ability to include syllables with weaker prosodic stress in
      multisyllabic productions. Omissions became much less common with the onset of 2
      word speech.

PMID- 9923464
TI  - Word learning in the context of referential and salience cues.
AB  - Adult referential behavior (gaze direction) and salience (target activation) were
      independently manipulated in a study of novel word learning. Children (seventy
      five 18-month-olds and seventy-two 24-month-olds) were trained in different
      conditions with a novel word in the context of 2 remote-controlled toys. In
      response to the novel word at test, 24-month-olds tended to pick out the toy to
      which the adult referred in all conditions. They also tended to use the novel
      word appropriately. Comprehension by 18-month-olds was good when the salience of
      the toy did not conflict with the adult's referential intent, but it was
      disrupted when referential and salience cues conflicted and when referential cues
      were not available. Results imply that, at 24 months, children use the
      referential intent of the speaker to learn new words, but when first learning
      words, children may have a less secure grasp on the meaning of speakers'
      referential cues.

PMID- 9923465
TI  - Children's goals and strategies in response to conflicts within a friendship.
AB  - Little is known about the skills required for friendship, as distinct from those
      required for peer acceptance. The present study examined whether children's goals
      and strategies in friendship conflict situations are predictive of their
      friendship adjustment, after accounting for level of peer acceptance. Fourth- and
      5th-grade children (N = 696) responded to 30 hypothetical situations in which
      they were having a conflict with a friend. Results indicated that children's
      goals were highly related to their strategies and that children's goals and
      strategies were predictive of their real-life friendship adjustment. Pursuing the
      goal of revenge toward a friend was the goal or strategy most strongly associated
      with lacking friends and having poor-quality friendships. Gender differences were
      also found for each goal and strategy, with girls displaying a more prosocial
      goal and strategy orientation than boys.

PMID- 9923466
TI  - Children's interactions in triads: behavioral profiles and effects of gender and
      patterns of friendships among members.
AB  - In all, 56 triads of same-sex 3rd-, 4th-, and 5th-grade children were observed
      during an intimate discussion, a cooperative puzzle task, a competitive game, and
      free play. Observers coded triadic interaction using a Q sort and individual
      process ratings. Of particular interest was how gender and the pattern of
      friendship ties among group members related to children's behavior. Triads of
      girls were more intimate, exchanged more information, and were less aggressive
      than were triads of boys. Analyses of within-gender variability revealed 2
      prototypical types of triads among boys but only 1 among girls. Girls and boys
      expressed similar attitudes toward triadic interaction in postsession interviews.
      However, girls', but not boys', attitudes were closely linked to the quality of
      interactions during the session. For both sexes, interaction was not strongly
      influenced by the initial configuration of friendship ties among triad members.

PMID- 9923467
TI  - The power of friendship: protection against an escalating cycle of peer
      victimization.
AB  - This study examined 2 aspects of friendship (presence and perceived qualities of
      a best friend) as moderators of behavioral antecedents and outcomes of peer
      victimization. A total of 393 children (188 boys and 205 girls) in the 4th and
      5th grades (mean age = 10 years 7 months) participated during each of 2 waves of
      data collection in this 1-year longitudinal study. Results indicated that teacher
      reported internalizing and externalizing behaviors predicted increases in peer
      reported victimization, but the relation of internalizing behaviors to increases
      in victimization was attenuated for children with a protective friendship.
      Victimization predicted increases in internalizing and externalizing behaviors
      but only for children without a mutual best friendship. Results highlight the
      importance of peer friendships in preventing an escalating cycle of peer abuse.

PMID- 9923468
TI  - Elementary school children's explicit and implicit memory for faces of preschool
      classmates.
AB  - This study examined elementary school children's memories for faces of preschool
      classmates after a 3-year interval. Children recognized their former classmates
      at an above-chance level, but their level of recognition was significantly lower
      than the level shown by the preschool teachers. Children showed implicit memory
      of classmates by making fewer errors while performing a face-matching task in
      classmate conditions than in control conditions. However, the classmate advantage
      on the face-matching task was found to decrease across the 3-year interval.
      Several findings in this study pointed to functional independence of implicit and
      explicit memory (e.g., children's explicit recognition memory, but not implicit
      memory, was related to amount of time children spent together at preschool).

PMID- 9923469
TI  - On facts and conceptual systems: young children's integration of their
      understandings of germs and contagion.
AB  - Five studies argue against claims that preschoolers understand a biological germ
      theory of illness. In Studies 1-3, participants were read stories in which
      characters develop symptoms (e.g., a bellyache) caused by germs, poisons, or
      events (e.g., eating too much candy) and were asked whether another character
      could catch the symptoms from the first. Few children made judgments in terms of
      germs as part of an underlying causal process linking the origin of a symptom to
      its subsequent transmission. Some children may have reasoned simply that certain
      kinds of symptoms are likely to be contagious. Studies 4 and 5 undermined the
      claim that preschoolers understand germs to be uniquely biological causal agents.
      Young children did not attribute properties to germs as they did for animate
      beings or for plants. It is suggested that children undergo conceptual
      reorganization in constructing a Western adult understanding of germs.

PMID- 9923470
TI  - How children change their minds: strategy change can be gradual or abrupt.
AB  - This study investigated patterns of change in children's strategies for solving
      mathematical equivalence problems. The strategies children expressed in speech
      and in gesture were assessed both before and after an instructional intervention.
      In the intervention, children received either no input, accuracy feedback, or
      feedback plus instruction about a principle, an analogy, or a procedure. From
      pretest to posttest, many children changed both the variability of their strategy
      use and the content of their strategy repertoires. Patterns of change depended on
      type of instruction and on children's initial level of variability. Children who
      received instruction were especially likely to generate new strategies, and
      children with high variability were especially likely to abandon prior
      strategies. Gradual change was most common; however, many children modified their
      repertoires abruptly. Abrupt strategy change was especially prevalent among
      children who received procedure-based instruction and among children with low
      initial variability.

PMID- 9923471
TI  - Information seeking and achievement motivation in middle childhood and
      adolescence: the role of conceptions of ability.
AB  - Two studies confirmed that maladaptive responses to failure in ego-involving
      settings depend on acquisition of the differentiated concept of ability (DCA) in
      early adolescence (J. G. Nicholls, 1984). Information seeking, performance, and
      interest in task versus ego-involving conditions were examined among 190 pupils
      in Grades 4 and 8 and 139 pupils in Grades 5-6 who had or had not acquired the
      DCA. Age and conception of ability had similar effects. Pupils who had acquired
      the DCA responded to the task condition with strivings to learn and requests for
      information relevant to acquiring mastery and to the ego condition with strivings
      to outperform others and requests for normative feedback. Failure undermined
      information seeking, performance, and interest in the ego condition only after
      acquisition of the DCA. Surprisingly, pupils who had not acquired the DCA
      responded to both conditions with strivings to assess normative success but
      displayed neither the costs of ego involvement nor the benefits of task
      involvement.

PMID- 9923472
TI  - Early fraction calculation ability.
AB  - Three- to 7-year-olds' ability to calculate with whole-number, fraction, and
      mixed-number amounts was tested using a nonverbal task in which an amount was
      displayed and then hidden (J. Huttenlocher, N. C. Jordan, & S. C. Levine, 1994).
      Next, an amount was added to or subtracted from the hidden amount. The child's
      task was to determine the hidden amount that resulted from the transformation.
      Although fraction problems were more difficult than whole-number problems,
      competence on all problem types emerged in the early childhood period.
      Furthermore, there were striking parallels between the development of whole
      number and fraction calculation. This is inconsistent with the hypothesis that
      early representations of quantity promote learning about whole numbers but
      interfere with learning about fractions (e.g., R. Gelman, 1991; K. Wynn, 1995,
      1997).

PMID- 9923473
TI  - Gender differences in emotional expressivity and self-regulation during early
      infancy.
AB  - Eighty-one 6-month-old infants and their mothers were videotaped in Tronick's
      face-to-face still-face paradigm to evaluate gender differences in infant and
      maternal emotional expressivity and regulation. Male infants had greater
      difficulty than female infants in maintaining affective regulation during each
      episode, including the still face. Mother-son dyads had higher synchrony scores
      than mother-daughter dyads but took longer in repairing interactive errors. In
      addition, maternal affect, matching, rate of change between matching and
      mismatching states, and synchrony in the play preceding the still face
      differentially mediated male and female infants' responses to the still face and
      reunion play. The developmental implications of these gender differences are
      discussed.

PMID- 9923474
TI  - Developmental models of infant and childhood temperament.
AB  - The developmental courses of specific temperamental constructs were explored by
      using structural equation model fitting. Maternal ratings were obtained from
      either 2 or 3 different temperament questionnaires for 180 children at 3, 6, 12,
      18, 24, 36, and 48 months of age. Several formal structural models were fit in
      infancy (3-18 months), in the toddler-preschooler period (24-48 months), and
      across all measurement occasions. In infancy, the autoregressive simplex model
      fit well for all 4 composites considered: Positive Emotionality, Distress-Anger,
      Fear, and Activity Level. In contrast to the considerable change in temperament
      during infancy, temperament appears to be very stable from 24 to 48 months of
      age, and a common factor model fits well with these data. Across all measurement
      occasions, models that allowed for stability in temperament to be at least
      partially mediated through intermediate forms of the trait fit best.

PMID- 9923475
TI  - Development of inhibitory control across the life span.
AB  - The stop-signal procedure was used to examine the development of inhibitory
      control. A group of 275 participants, 6 to 81 years of age, performed a visual
      choice reaction time (go) task and attempted to inhibit their responses to the go
      task when they heard a stop signal. Reaction times to the stop and go signals
      were used to assess performance in inhibition and response execution,
      respectively. Results indicated the speed of stopping becomes faster with
      increasing age throughout childhood, with limited evidence of slowing across
      adulthood. By contrast, strong evidence was obtained for age-related speeding of
      go-signal reaction time throughout childhood, followed by marked slowing
      throughout adulthood. Hierarchical regression confirmed that the age-related
      change in inhibitory control could not be explained by general speeding or
      slowing of responses. Findings are discussed in regard to the contrast between
      the development of inhibition and response execution and the utility of the stop
      signal procedure.

PMID- 9923476
TI  - Entry behavior and emotion regulation abilities of developmentally delayed boys.
AB  - This study investigated the social deficits of developmentally delayed children.
      Participants were 48 five-year-old to eight-year-old boys. Delayed children (n =
      20) were compared with nondelayed children of similar chronological age (CA
      nondelayed; n = 20) and of similar mental age (n = 8). The behavior and emotion
      regulation strategies of participants were assessed in an analogue entry
      situation. Delayed children were just as able as nondelayed children to
      understand the play themes of others but were more intrusive in delivering their
      entry attempts. Delayed children appeared to have less effective emotion
      regulation strategies for coping with entry failure and were more likely to
      increase their use of disruptive entry strategies over time than CA nondelayed
      children.

PMID- 9923477
TI  - Mother-infant affect synchrony as an antecedent of the emergence of self-control.
AB  - This study examined relations between mother-infant affect synchrony and the
      emergence of children's self-control. Mother-infant face-to-face play and infant
      difficult temperament were examined at 3 and 9 months. Maternal and infant
      affective states at play were coded in 0.25-s frames, and synchrony was computed
      with cross-correlation functions. Self-control, verbal IQ, and maternal warm
      discipline were assessed at 2 years. Maternal synchrony with infant affect at 3
      months (infant-leads-mother-follows relation) and mutual synchrony at 9 months
      (cross-dependence between maternal and infant affect) were each related to self
      control at 2 years when temperament, IQ, and maternal style were partialed.
      Infant temperament moderated the relations of synchrony and self-control, and
      closer associations were found between mutual synchrony and self-control for
      difficult infants. Shorter lags to maternal synchrony at 3 months were
      independently related to self-control. The mutual regulation of affect in
      infancy, as moderated by temperament, is proposed as an important contributor to
      the emergence of self-regulation.

PMID- 9923478
TI  - The emergence of gender difference in depressed mood during adolescence: the role
      of intensified gender socialization.
AB  - The prevalence of depressive mood was examined in a representative and nationwide
      sample of approximately 12,000 Norwegian adolescents. From the age of 14, girls
      scored 0.5 SD above boys in depressed mood, a difference that was stable
      throughout the adolescent period. At the age of 12, no gender difference was
      found. The gender difference was due to girls becoming more depressed from 13 to
      14 years of age. An extended version of the gender intensification hypothesis (J.
      P. Hill & M. E. Lynch, 1983) was tested as an explanation for the gender
      difference in depressed mood. Structural equation modeling and regression
      analyses showed that the gender difference could be explained, in part, by
      increased developmental challenges for girls--pubertal development,
      dissatisfaction with weight and attainment of a mature female body, and increased
      importance of feminine sex role identification. Depressed mood was not associated
      with masculinity or school change, as had been predicted.

PMID- 9923479
TI  - Homelessness and its relation to the mental health and behavior of low-income
      school-age children.
AB  - This study examined the relationship between housing status and depression,
      anxiety, and problem behaviors among children age 6 and older who were members of
      low-income, single-parent, female-headed families. Participants were 80 homeless
      and 148 never homeless children living in Worcester, Massachusetts. Children in
      both groups had recently been exposed to various severe stressors. Mother
      reported problem behaviors were above normative levels for both homeless and poor
      housed youths but self-reported depression and anxiety were not. Controlling for
      other explanatory variables, housing status was associated with internalizing
      problem behaviors but not with externalizing behaviors. Among homeless youths,
      internalizing behavior problems showed a positive but curvilinear relationship
      with number of weeks having lived in a shelter. Housing status was not associated
      with self-reported depression and anxiety. Findings are discussed in terms of
      their implications for programmatic interventions and in light of recent welfare
      reform.

PMID- 9923480
TI  - Family instability and the problem behaviors of children from economically
      disadvantaged families.
AB  - This longitudinal study examined the relation between family instability and the
      problem behaviors of children from economically disadvantaged families. Family
      instability was assessed when the children were ages 5 and 7 and included number
      of residence changes, changes of intimate caregiver relationships, and recent
      negative life events. The results showed direct concurrent relations between
      family instability and preschool children's externalizing behavior in the context
      of other family process variables, relations between subsequent family
      instability and 1st-grade children's internalizing behavior (i.e., with preschool
      behavior ratings controlled), and an effect for persistent instability across
      grade. Moderator effects were also found for child variables, including gender,
      temperamental adaptability, and prior externalizing scores.

PMID- 9923481
TI  - Maltreated and nonmaltreated preschoolers' conceptions of hypothetical and actual
      moral transgressions.
AB  - Maltreated and nonmaltreated preschoolers' (mean age = 4 years 6 months)
      judgments regarding hypothetical and actual moral transgressions were examined.
      Thirty-six maltreated children (17 physically abused and 19 neglected) and 19
      comparison nonmaltreated children judged, justified, and evaluated affective
      responses to 6 hypothetical moral transgressions. Perpetrators and victims also
      judged and evaluated affective responses to actual classroom moral
      transgressions. All children evaluated moral transgressions as very serious,
      punishable, and wrong in the absence of rules. Moral judgments and justifications
      differed as a function of context (hypothetical vs. actual) and type of
      transgression but not maltreatment status. Affective responses differed as a
      function of maltreatment subtype and gender. Maltreated and nonmaltreated
      children may differ in the organization of their affective responses rather than
      in their moral evaluations.

PMID- 9923482
TI  - Infant arousal in an en-face exchange with a new partner: effects of prematurity
      and perinatal biological risk.
AB  - Very low birth weight (VLBW) infants of higher (n = 18) and lower (n = 29)
      perinatal biological risk were contrasted at 4 months adjusted age with healthy
      full-term infants (n = 32) in their arousal during a standardized peekaboo game
      with an examiner. VLBW infants showed less positive arousal, more negative
      arousal, and 3 mixtures of behavioral cues across the peekaboo game seldom seen
      for full-term infants-strong cues of both positive and negative arousal, strong
      cues of negative arousal alone, and no strong cues of either positive or negative
      arousal. Contrary to expectations, perinatal biological risk did not strongly
      predict variations in arousal within the VLBW group. Possible changes in how
      internal and external sources of arousal are integrated provide one explanation
      for the presence of strong relationships between perinatal biological risk and
      social responsiveness near term age and their disappearance by 4 months of age.

PMID- 9923483
TI  - Electrophysiological evidence of developmental changes in the duration of
      auditory sensory memory.
AB  - In behavioral studies, children's memory for tonal frequency has been found to
      persist for less time than adults' (T. A. Keller & N. Cowan, 1994). The present
      study was done to evaluate the argument that this effect is due to changes in
      auditory sensory memory and not to attentional mechanisms. This question was
      investigated using mismatch negativity (MMN), an auditory event-related potential
      considered to be insensitive to attention. Participants were 6-7-, 8-10-, and 11
      12-year-old children and adults. They were presented with trains of stimuli,
      beginning with either a standard (1000 Hz) or a deviant (1200 Hz) tone with
      trains separated by either 1 s or 8 s. All 4 groups exhibited MMNs after delays
      of 1 s, but only the adults and oldest children exhibited MMNs after 8 s,
      indicating that there are maturational changes in the duration of auditory
      sensory memory.

PMID- 9923484
TI  - Seeing it happen and knowing how it works: how children understand the relation
      between perceptual causality and underlying mechanism.
AB  - Two experiments studied how 5- to 10-year-olds integrate perceptual causality
      with their knowledge of the underlying causal mechanism. Children learned about 2
      devices by which a ball dropped into one end of a box made a bell ring at the
      other end, either immediately (contiguous mechanism) or after a delay
      (noncontiguous mechanism). When 1 ball was dropped first and a 2nd ball was
      dropped after a delay, and then the bell rang immediately, 5- and 7-year-olds
      chose the contiguous cause regardless of the mechanism inside. This was not due
      to lack of specific knowledge or problems with salient distractors. The results
      suggest a link between temporal contiguity and causality in children's
      understanding. Children also considered causal mechanism, in agreement with
      previous research, but they may not understand that mechanism is superordinate to
      perceptual cues for causality.

PMID- 9923485
TI  - Small incision cataract surgery and placement of posterior chamber intraocular
      lenses in patients with diabetic retinopathy.
AB  - BACKGROUND AND OBJECTIVE: Diabetic patients undergoing cataract surgery have been
      demonstrated to have a guarded prognosis. Small incision cataract surgery has
      been postulated to cause fewer complications than other techniques of cataract
      extraction. We looked at small incision cataract surgery to see how diabetics
      fared. PATIENTS AND METHODS: One hundred fifty-four eyes of diabetic patients
      were evaluated preoperatively through dilated fundus examination and Snellen
      visual acuity. The eyes then underwent small incision cataract surgery and were
      followed, undergoing periodic ophthalmoscopy, Snellen visual acuity measurement
      and additional postoperative therapeutic and surgical intervention. RESULTS:
      Final visual acuity improved by two Snellen lines or more in 61 out of 154 (40%)
      eyes. Final visual acuity worsened in 38 out of 154 (25%) eyes. CONCLUSIONS: Our
      results are similar to those reported for extracapsular surgery and
      phacoemulsification, suggesting that the prognosis is guarded for diabetics, even
      when undergoing small incision cataract surgery.

PMID- 9923486
TI  - Decreased prevalence of retinopathy of prematurity in an inner-city hospital.
AB  - BACKGROUND AND OBJECTIVE: Improvements in care of low birth weight preterm
      infants has led to an increased survival of this population. It is not known
      whether the improved care has decreased the prevalence of retinopathy of
      prematurity (ROP), or whether the survival of even smaller infants has increased
      the prevalence. The purpose of this study was to determine the prevalence of ROP
      in an inner-city hospital during two time periods to determine whether the
      prevalence is changing. PATIENTS AND METHODS: The frequency and characteristics
      of ROP were compared between a 10-month observation period in 1995-1996 and
      published data from a similar time period in 1988-1989. RESULTS: There were fewer
      cases of ROP per live births less than 1500 g during 1995-1996 compared with 1988
      1989 (P< .0001). This included both mild and severe ROP. When the two racial
      subgroups were examined separately, there was a statistically significant decline
      for the black (P < .001) but not the Hispanic population (P = .12). The Mantel
      Haenszel chi2 test confirmed that the decline was statistically significant when
      the two groups were combined (P < .001). CONCLUSIONS: In this population, the
      prevalence of ROP appears to have decreased between 1995-1996 and 1988-1989. The
      subgroup experiencing the biggest decline was black infants. Other studies should
      be performed to investigate whether the frequency of ROP has also declined in
      other settings.

PMID- 9923487
TI  - Total internal reflection of laser light in eyes filled with silicone oil.
AB  - BACKGROUND AND OBJECTIVES: This is the first report of clinical settings in which
      total internal reflection of laser light in eyes filled with silicone oil was
      observed. The authors analyze this phenomenon and outline the potential hazards
      it may present to patient, surgeon, and operating room personnel. MATERIALS AND
      METHODS: The authors observed significant reflection of laser light off the
      silicone-water interface both intraoperatively and in the clinic. The critical
      angle according to Snell's law (i.e., the angle at which total internal
      reflection occurs at the interface between silicone oil and vitreous) was
      calculated. The critical angle was found to be 71.9691 degrees(72 degrees).
      RESULTS: An analysis of each of the clinical conditions where this phenomenon was
      observed is presented. Clinical and surgical implications are discussed.
      CONCLUSIONS: The hazard of total internal reflection of laser light in eyes
      filled with silicone oil should be recognized by ophthalmologists to avoid
      possible complications. Techniques for overcoming and circumventing the
      difficulties resulting from this phenomenon are proposed.

PMID- 9923488
TI  - Silicone oil removal using a self-sealing corneal incision under topical
      anesthesia.
AB  - BACKGROUND AND OBJECTIVE: To report the results of silicone oil removal from
      aphakic eyes using a self-sealing clear corneal incision under topical
      anesthesia. PATIENTS AND METHODS: Twenty-two eyes of 22 patients who had pars
      plana vitrectomy combined with silicone oil injection underwent silicone oil
      removal under topical anesthesia using a self-sealing clear corneal incision.
      Mean time between silicone oil injection and removal was 3.1+/-1.42 months.
      Fourteen eyes were filled with 1300 cs of silicone oil and 8 eyes were filled
      with 5700 cs of silicone oil. The removal was performed with passive washout in
      the eyes filled with 1300 cs of silicone oil and with active aspiration in the
      eyes filled with 5700 cs of silicone oil. RESULTS: All of the 22 silicone oil
      removal procedures performed under topical anesthesia had clear corneal incisions
      that did not require suturing at the end of surgery. Three cases that had 1300 cs
      of silicone oil required aspiration because of residual silicone oil bubbles.
      CONCLUSION: Silicone oil can be removed from the aphakic eye using a self-sealing
      corneal tunnel incision under topical anesthesia.

PMID- 9923489
TI  - Intraoperative stress experienced by surgeons and assistants.
AB  - BACKGROUND AND OBJECTIVE: To determine the intraoperative stress on surgeons and
      assistants during cataract surgery, 12 surgeons and 3 assisting nurses were
      assessed based on their level of professional experience. METHODS: Surgeons were
      classified as inexperienced, intermediate, or experienced. Nurse assistants were
      classified as inexperienced or experienced. The intraoperative heart rates and
      urine adrenaline levels of each participant were measured. RESULTS: Inexperienced
      surgeons and nurse assistants had the highest heart rates at the beginning of
      surgery, and the rates tended to decrease toward the end of surgery. All values
      were higher than the other two groups throughout surgery. In surgeons with
      intermediate experience, the heart rates were not as high as in the inexperienced
      personnel; however, the heart rates were high throughout the surgery. The heart
      rate in one intermediate surgeon was markedly increased when a surgery was
      simultaneously broadcast on closed-circuit television. In experienced surgeons
      and a nurse assistant, the measurements increased slightly. CONCLUSIONS: The
      variations in heart rates and urine adrenaline levels showed characteristic
      patterns based on the experience of the surgical personnel.

PMID- 9923490
TI  - Sclerokeratoplasty versus penetrating keratoplasty in anterior staphyloma.
AB  - BACKGROUND AND OBJECTIVE: To assess the efficacy of the newer surgical technique
      of sclerokeratoplasty in spherical anterior staphyloma of the cornea and to
      compare it with total penetrating keratoplasty. PATIENTS AND METHODS: A
      randomized, prospective clinical trial in 20 eyes with acquired spherical
      anterior staphylomas was undertaken. Ten eyes each underwent sclerokeratoplasty
      (group 1) or total penetrating keratoplasty (group 2). The parameters evaluated
      were visual acuity, keratometry, graft status, and complications. Patients were
      observed for a minimum of 1 year. RESULTS: Best spectacle-corrected visual acuity
      of 6/60 or better with astigmatism of less than 3 D was achieved in all but one
      patient in group 1 in contrast to 5 cases in group 2. Postoperative complications
      included epithelial defects, shallow anterior chamber, hyphema, and uveitis,
      which did not significantly vary between the 2 procedures. Secondary glaucoma was
      significant associated with group 2 as compared with group 1. At the end of 1
      year, no significant difference in the graft clarity was present. Grafts were
      clear 3+ or more in 8 eyes in group 1 and in 5 eyes in group 2. Good cosmetic
      results were achieved in cases of sclerokeratoplasty due to the absence of
      corneal opacification and suture marks. CONCLUSION: Sclerokeratoplasty is a
      useful alternative to total penetrating keratoplasty in cases of acquired
      spherical anterior staphylomas of the cornea with good anatomic and useful visual
      outcome.

PMID- 9923491
TI  - Intraocular pressure reduction following phacoemulsification cataract extraction
      with posterior chamber lens implantation in glaucoma patients.
AB  - BACKGROUND AND OBJECTIVE: To evaluate changes in intraocular pressure (IOP)
      following uneventful phacoemulsification cataract extraction with posterior
      chamber intraocular lens implantation (Phaco/PC IOL) in primary open-angle
      glaucoma (POAG) patients. PATIENTS AND METHODS: The authors retrospectively
      reviewed preoperative and postoperative IOP in 31 consecutive medically
      controlled POAG patients who underwent uneventful Phaco/PC IOL. None of the
      patients had prior intraocular surgery. RESULTS: The mean preoperative IOP in the
      POAG group was 18.1+/-3.1 mm Hg with patients receiving a mean of 1.7
      antiglaucoma medications. With a mean follow-up of 16.4 months, the average
      postoperative IOP in the POAG group was 15.2+/-2.9 mm Hg (P < .001, Student's t
      test) with patients receiving a mean of 0.7 antiglaucoma medication (P < .001).
      CONCLUSION: Phaco/PC IOL may be associated with a significant decrease in IOP in
      POAG patients, allowing for decreased postoperative antiglaucoma medication.

PMID- 9923492
TI  - Surgical revision of glaucoma shunt implants.
AB  - BACKGROUND AND OBJECTIVE: To determine the efficacy of surgical revision of
      glaucoma shunt implants in patients with advanced glaucoma. PATIENTS AND METHODS:
      The records of 13 patients who underwent revision of their shunt implants were
      retrospectively reviewed. RESULTS: Surgical success was achieved in: 3 of 3
      patients (100%) with drainage tube malposition or extrusion; 1 of 6 patients
      (17%) with occlusion of the intracameral portion of the drainage tube; and 1 of 4
      patients (25%) with elevated intraocular pressure secondary to fibrous capsule
      formation over the implant. CONCLUSIONS: Surgical revision of glaucoma shunt
      implants is a useful procedure in patients who develop tube malposition or
      extrusion. Surgical revision is much less effective in patients with tube
      occlusion or fibrous capsule formation. Failure of the shunts due to recurrent
      fibrosis is commonly observed.

PMID- 9923493
TI  - Extrusion and granuloma formation with mersilene mesh brow suspension.
AB  - BACKGROUND AND OBJECTIVE: A variety of biologic or synthetic materials have been
      used in brow suspension ptosis surgery. We describe extrusion and granuloma
      formation in 5 cases of congenital ptosis operated with Mersilene mesh sling.
      PATIENTS AND METHODS: Case reports with review of literature. RESULTS: Two cases
      of extrusion and 3 cases of granuloma formation were encountered in 79 eye lids
      of 52 (6.3%) patients performed for the treatment of congenital ptosis. Mersilene
      mesh fibers in the cut surface and a foreign body reaction were found by
      microscopic evaluation of tissue harvested at the time of surgical removal of the
      sling. CONCLUSION: Despite the operative precautions, the probability of
      extrusion and granuloma formation should be in mind in cases of congenital ptosis
      operated with Mersilene mesh sling, a synthetic material.

PMID- 9923494
TI  - Chorioretinal venous anastomosis for central retinal vein occlusion: transvitreal
      venipuncture.
AB  - The authors describe an eye with a central retinal vein occlusion that developed
      chorioretinal anastomoses following transvitreal venipuncture, a vitreoretinal
      surgical technique.

PMID- 9923495
TI  - Krypton laser photocoagulation of peripapillary choroidal neovascular membrane.
AB  - The Macular Photocoagulation Study criteria require that at least 1.5 clock hours
      of temporal peripapillary retina be spared when treating choroidal neovascular
      membrane in that location. The authors successfully treated peripapillary
      choroidal neovascular membrane involving temporal 180 degrees with the krypton
      laser without any loss of visual acuity and central field.

PMID- 9923497
TI  - Lacrimal sac dilatation in balloon dacryocystoplasty.
AB  - The authors report a case of balloon dacryocystoplasty in a patient who had a
      dilated lacrimal sac found in conventional surgery. A 52-year-old woman presented
      with persistent epiphora after a failed balloon dacryocystoplasty. She underwent
      an external dacryocystorhinostomy. The lacrimal sac was found to be dilated at
      its lower part, adjacent to the nasolacrimal ductus. Flaps were created more
      superiorly than usual. The operation was unsuccessful after 3 months. Previous
      balloon dacryocystoplasty, which is reported to be a harmless procedure, may pose
      some difficulty in subsequent conventional surgery.

PMID- 9923496
TI  - Penetrating eye injury from a metal wedge.
AB  - The authors describe a patient with a penetrating ocular injury from a metal
      wedge, a common hand tool used by road service technicians for the purpose of
      opening a locked car door. The patient had a penetrating eye injury from a metal
      wedge when its sharp end released from a car door lock and retracted upward,
      striking the right eye. No report exists of ocular injury using a metal wedge for
      its intended purpose of opening a car door lock. The use of polycarbonate lenses
      might afford some protection.

PMID- 9923498
TI  - A simple "lasso" for intraocular foreign bodies.
AB  - Three patients had foreign bodies in their anterior chambers following
      penetrating ocular injuries. These foreign bodies were removed by a closed
      chamber technique using a simple loop. The loop was created by a 22-gauge
      intravenous cannula and a 7-0 polypropylene suture. Retained cilia in one patient
      and metallic foreign bodies in two patients were removed using this intraocular
      "lasso." Sutures were not placed at the incision sites at the end of the surgery.
      This is an inexpensive and easy to prepare technique that introduces minimal
      surgical trauma. In addition, two hands are not needed for loop manipulation.
      This technique may be an excellent alternative for removal of small intraocular
      foreign bodies.

PMID- 9923499
TI  - The continuous-injection technique to reduce complications during retrobulbar
      anesthesia.
AB  - Retrobulbar as well as peribulbar anesthesia remain relatively risky procedures;
      retrobulbar hemorrhage and especially globe penetration or perforation can have
      blinding consequences. Our continuous-injection-technique greatly reduces these
      risks whether used for retrobulbar or peribulbar anesthesia. If the
      ophthalmologist starts injecting the agent while advancing the needle, the fluid
      pushes tissues away, possibly preventing a hemorrhage. Since resistance against
      the plunger is instantaneously experienced if the needle impacts the sclera, the
      ophthalmologist is adequately warned before actual perforation of the sclera
      occurs.

PMID- 9923500
TI  - The use of rectus abdominis sheath for wrapping of the hydroxyapatite orbital
      implants.
AB  - Because of the decreasing availability of whole eye donation, the source of
      banked sclera is becoming less available. We used autogenous Rectus abdominis
      sheath (RAS) as an alternative to banked sclera in wrapping the hydroxyapatite
      (HA)orbital implant. Five anophthalmic patients were included in this study from
      July 1994 to December 1997. Identical surgical methods were used in every case.
      The average follow-up time was 18.4 months. The motility associated with sheath
      wrapped HA implants was excellent and good vascular ingrowth was found in each
      patient during peg drilling. The complications are minimal in all the cases. Use
      of RAS as wrapping material for HA orbital implant has promising results. The RAS
      served as a practical substitute for banked donor sclera.

PMID- 9923501
TI  - Quantitative image sequence analysis of fundus fluorescein angiography.
AB  - Interpretation of retinal angiographic studies has heretofore been largely
      qualitative. The temporal properties associated with fluorescein fluorescence of
      normal and pathologic fundus features are quantified to potentiate pixel
      assignment and fundus feature quantitation for clinical studies where precise
      image metrology is vital. Fluorescein angiography studies were digitized, and
      temporally sequential images were spatially registered with polynomial warping
      algorithms, allowing for the construction of a three-dimensional angiogram
      vector. Temporal profiles through spatially registered, temporally sequential
      pixels were computed. Fundus feature fluorescence behavior was quantified. Fundus
      features may be discriminated on the basis of spatio-temporal fluorescein
      fluorescence properties. Pixel assignment based on spatio-temporal relationships
      will facilitate fundus feature quantitation.

PMID- 9923502
TI  - Factors affecting image acquisition during scanning laser polarimetry.

PMID- 9923503
TI  - Increase of crevicular interleukin 1beta under academic stress at experimental
      gingivitis sites and at sites of perfect oral hygiene.
AB  - This study analyses the effects of academic stress on crevicular interleukin
      1beta(I1-1beta) both at experimental gingivitis sites and at sites of perfect
      oral hygiene. I1-1beta is thought to play a predominant role in periodontal
      tissue destruction. 13 medical students participating in a major medical exam
      (exam group) and 13 medical students not participating in any exam throughout the
      study period (control group) volunteered for the study. In a split-mouth-design,
      they refrained from any oral hygiene procedures in two opposite quadrants for 21
      days (experimental gingivitis) while they maintained perfect hygiene levels at
      the remaining sites. Crevicular fluid was sampled for further I1-1beta analysis
      at teeth 5 and 6 of the upper jaw at days 1, 5, 8, 11, 14, 18 and 21 of the
      experimental gingivitis period. Exam students showed significantly higher I1
      1beta levels than controls both at experimental gingivitis sites (area under the
      curve, exam group: 1240.64+/-140.07; control group: 697.61+/-111.30; p=0.004) and
      at sites of perfect oral hygiene (exam group: 290.42+/-63.19; control group:
      143.98+/-42.71; p = 0.04). These results indicate that stress might affect
      periodontal health by increasing local I1-1beta levels especially when oral
      hygiene is neglected.

PMID- 9923504
TI  - Tobacco smoking and gingival neutrophil activity in young adults.
AB  - The influence of smoking on the activity of the gingival neutrophils in young
      periodontally healthy adults was studied. The neutrophil activity was measured in
      terms of the gingival crevicular fluid (GCF) levels of elastase, lactoferrin
      (LF), alpha-1-antitrypsin (alpha-1-AT), alpha-2-macroglobulin (alpha-2 MG) and
      protein. 30 healthy dental students with no clinical signs of periodontitis, 15
      smokers (8 women and 7 men) aged 20-32 years and 15 non-smokers (7 women and 8
      men) aged 22-31 years, volunteered to take part in the investigation. The
      gingival inflammation was registered at 6 sites and the GCF volume was collected
      from the same sites. The GCF volume was measured with a Periotron 6000. The
      elastase activity was measured with a chromogenic low molecular substrate and the
      LF alpha-1-AT, alpha-2-MG levels were determined with ELISA. The protein
      concentration was measured by the Bradford method. The results showed a
      statistically significantly lower GCF volume among smokers as compared to non
      smokers. No significant difference was found in the elastase activity/microl of
      the GCF supernatant between smokers and non-smokers but there was a large inter
      individual variation. Nor did the concentrations of LF, alpha-1-AT, alpha-2-MG
      and protein per microl GCF differ significantly between the 2 groups. The results
      suggest that the influence of smoking on the examined factors associated with
      neutrophil activity is limited under healthy or slightly inflamed gingival
      conditions giving only small amounts of GCF.

PMID- 9923505
TI  - Retention of fluoride/triclosan in plaque following different modes of
      administration.
AB  - The aim of the present investigation was to compare: (i) de novo plaque
      formation, and (ii) fluoride and triclosan concentration in approximal plaque,
      when a NaF/triclosan/Gantrez-containing dentifrice slurry or a mouthrinse were
      administrated during a 2-week period of no mechanical plaque control. 10 subjects
      rinsed for 60 s, 2x daily, for a 14-day period with one of the following 3 test
      products: (A) a dentifrice slurry including 1 ml of a NaF/triclosan/Gantrez
      dentifrice mixed with 10 ml of tap water, (B) 10 ml of a NaF/triclosan/ Gantrez
      mouthrinse, or (C) 10 ml of a NaF mouthrinse. De novo plaque formation was
      assessed on days 4, 7 and 14 using the Turesky's modification of the Quigley and
      Hein index system. Samples of approximal plaque were obtained immediately after
      clinical examination on day 14. The samples were analyzed with respect to
      concentration of fluoride and triclosan using an ion-specific electrode and a
      HPLC system, respectively. The 14-day period was repeated using another test
      product until all 10 subjects had used all 3 test products in a randomized order.
      The results showed that: (i) significantly more fluoride was retained in the
      approximal plaque following periods A and B than period C, and (ii) less plaque
      was formed during period B than periods A and C.

PMID- 9923506
TI  - Microbiological features and crevicular fluid aspartate aminotransferase enzyme
      activity in early onset periodontitis patients.
AB  - Gingival crevicular fluid (GCF) reflects the immune and inflammatory reactions
      and the specific host-microbe interactions that lead to periodontal diseases.
      Aspartate aminotransferase enzyme (AST) is one of the components of GCF that is
      released as a result of cell death. In this study, periodontal sites (4
      sites/patient) with a probing depth of > or =5 mm in early onset periodontitis
      (EOP) patients were first examined for the AST levels in GCF by the Periogard
      periodontal tissue monitor. To be eligible for the study, each of the patients
      had at least 1 AST positive site with clinical inflammatory changes (AST+, CIC+)
      and 1 AST negative site with no or minimum clinical inflammatory changes (AST-,
      CIC-). In 15 EOP patients who met the entry criteria, 30 AST+, CIC+ sites (1st
      group) and 19 AST-, CIC- sites (2nd group) were evaluated for microbiological
      variables. Certain microbial species, including Porphyromonas gingivalis,
      Actinobacillus actinomycetemcomitans and Prevotella intermedia were detected more
      frequently (p<0.001, p<0.001 and p<0.05, respectively) in the 1st group, while
      gram-positive facultative organisms such as Actinomyces species were found more
      often (p<0.001) in the 2nd group. Parallel to the AST levels, the 2nd group had a
      lower number of total bacteria and proportion of obligate anaerobic and
      capnophilic micro-organisms than the first group (p<0.05 and p<0.05,
      respectively). Within the scope of this study, AST activity and microbiological
      data were found in agreement in the examined groups. These findings are
      encouraging and indicate the need for further studies to evaluate the ability of
      the AST test to differentiate the microbial flora of progressing sites and those
      that are inflamed, but not progressing.

PMID- 9923507
TI  - A cross-sectional study into the prevalence of root caries in periodontal
      maintenance patients.
AB  - The aim of this cross-sectional study was to investigate cross-sectionally the
      prevalence and several risk indicators of root caries in 45 periodontal
      maintenance patients, who had been actively treated for adult periodontitis 11-22
      years ago. These patients were part of a routine 3-6 monthly maintenance
      schedule. Active and inactive root caries and root fillings were recorded, as
      well as coronal caries experience. Plaque and bleeding scores, number of exposed
      root surfaces, rate of saliva secretion, saliva buffering capacity, mutans
      streptococci counts and Lactobacilli were also scored. From the total of 45 study
      subjects, 37 patients (82%) showed root lesions (root caries and/or root
      fillings), while only 8 patients were free of any root lesions. On average, there
      were 4.3 root lesions per patient (range 0-19) in the present study. 10 patients
      had active root caries lesions. Of all damaged root surfaces, 9% were active
      lesions, mostly located on mandibular teeth at lingual and vestibular sites: 40%
      were inactive lesions often detected at vestibular sites. The remaining damaged
      root surfaces (51%) were restored; they were equally divided over both jaws. A
      higher number of root lesions was observed in those patients with >106 mutans
      streptococci/ml saliva. Although the actual number of lesions per patient was low
      in relation to the large number of sites with gingival recession, the results
      from this cross-sectional study in periodontal maintenance patients indicate
      that: (1) root caries can be regarded as a complication in periodontal
      maintenance patients; (2) the individual number of root lesions correlate with
      individual dental plaque scores; (3) a high number of root lesions is associated
      with high counts of salivary mutans streptococci; (4) no relation between root
      caries and coronal caries experience, salivary secretion rate or salivary
      buffering capacity seems present. Therefore, repeated oral hygiene instructions
      and adjunctive preventive measures including diet counseling and fluoride rinses,
      as well as fluoride and chlorhexidine varnishes, should be advocated in high-risk
      patients.

PMID- 9923508
TI  - Action potential conduction block of nerves in vitro by potassium citrate,
      potassium tartrate and potassium oxalate.
AB  - OBJECTIVES: Potassium salts in desensitising formulations are believed to act by
      blocking nerve conduction. The aim of this study was to assess the ability of
      some organic potassium salts to block action potential conduction and to compare
      their effects with potassium chloride and potassium nitrate. MATERIALS AND
      METHOD: Potassium citrate, oxalate or tartrate were added to Krebs' solutions to
      raise the potassium concentration to 8-64 mM. The test solutions were applied to
      rat spinal nerves in a bath while monitoring the compound action potentials
      evoked by electrical stimulation. RESULTS: All potassium salts attenuated the
      compound action potential in a dose-dependent manner. There were no significant
      differences between the effects of potassium tartrate and potassium citrate
      solutions (p>0.1) which caused significantly greater compound action potential
      attenuation than the same concentrations of potassium oxalate (p<0.05). On the
      basis of the potassium ion concentration required to cause 50% attenuation of the
      compound nerve action potential, the relative potencies of the potassium salts
      were: citrate = tartrate> oxalate>chloride =nitrate. CONCLUSION: Potassium
      citrate and potassium tartrate were more effective than other potassium salts in
      blocking nerve conduction and may be more effective dentinal desensitising
      agents.

PMID- 9923509
TI  - Periodontal probing depth and subgingival temperature in smokers and non-smokers.
AB  - The aim of this study was to investigate the difference in subgingival
      temperature between smokers and non-smokers at different probing depths, and the
      effect of probing depth on subgingival temperature for smokers and non-smokers.
      20 smokers and 20 non-smokers, with adult periodontitis, and retained upper
      anterior teeth were included. Initially sublingual temperatures were recorded,
      followed by subgingival temperature, pocket probing depth, and bleeding upon
      probing measurements at 3 buccal points at probing depths of 2, 3, 4, 5, and 6 mm
      for each of the anterior teeth. Sublingual temperatures were consistently higher
      than subgingival temperatures. The subgingival temperature measurements of
      pockets which bled upon probing, were subtracted from the sublingual temperature
      to produce temperature differentials (delta T), independent of individual body
      temperature, that were compared between smokers and non-smokers. The relationship
      between probing depth and delta T was examined in, and between, smokers and non
      smokers for bleeding sites. delta T was found to decrease linearly with the
      increase of probing depth, suggesting a subsequent increase of subgingival
      temperature. Smokers were found to have significantly increased delta
      T(suggesting lower subgingival temperatures) compared to non-smokers, at probing
      depths of 2, 3, 4, and 5 mm. The differences in delta T for sites 6 mm in depth
      were not statistically significant between the 2 groups. It is concluded that for
      maxillary buccal anterior sites, there is a decrease of temperature differentials
      with an increase of probing depth at bleeding sites for both smokers and non
      smokers. Smokers had higher temperature differentials compared to non-smokers, at
      probing depths of 2, 3, 4 and 5 mm.

PMID- 9923510
TI  - Prevalence and distribution of bone defects in moderate and advanced adult
      periodontitis.
AB  - The purpose of the present investigation was to evaluate the prevalence and
      distribution of different forms of bone defects using direct observation during
      periodontal surgery. 286 patients with moderate or advanced adult periodontitis
      diagnosed during clinical and radiographic examination provided a sample of 5476
      teeth. After full thickness mucoperiosteal flaps were raised, osseous defects
      were explored and classified according to their morphology as interdental
      craters, hemisepta and infrabony defects with 1, 2, 3 or 4 osseous walls. 981
      defects were detected; 533 were in the maxilla and 448 in the mandible (15.4% and
      22.4%, respectively, of the teeth examined). The posterior mandibular segment had
      the highest % of teeth with defects (33.8%) followed by the posterior maxillary
      segment (19.9%). The proportions of teeth with defects in the anterior segments
      of both arches were similar. The comparison between maxilla and mandible showed a
      highly significant difference for the posterior segments (p= 0.00001) but no
      difference for the anterior segments (p=0.88). The distribution of defects
      differed between the maxilla and the mandible, both for the posterior and
      anterior segments. Craters accounted for almost half the defects, being more
      prevalent in posterior segments, while hemisepta formed the lowest proportion.
      Anatomical variations in shape and the original morphology of the alveolar bone
      between the maxilla and the mandible and the anterior and posterior regions might
      have been the reason for the differences observed.

PMID- 9923511
TI  - Effects of nicotine on periodontal ligament fibroblasts in vitro.
AB  - Cigarette smoking is associated with increased incidence of periodontal disease
      and poor response to therapy. In the present study, we examined the effects of
      nicotine on several functions of periodontal ligament fibroblasts (PDLF):
      proliferation, attachment, alkaline phosphatase production and chemotaxis.
      Nicotine concentrations varying from 5 ng/ml to 250 microg/ml were tested.
      Proliferation of cells was studied by the incorporation of 3H-thymidine, and a
      dose-dependent inhibition was observed with concentrations > or =100 ng/ml.
      Similar results were observed when studying the attachment of the cells on
      plastic surfaces, using a colorimetric method. The inhibition of attachment was
      even more evident after 6 h incubation of the cells with nicotine. The activity
      of alkaline phosphatase, as determined with the substrate p-nitrophenyl
      phosphate, in both conditioned medium (CM) and cellular extract (CE), was also
      significantly decreased in a concentration-related fashion. Finally, the
      chemotaxis of PDLE as examined by a modification of the Boyden's blind-well
      chamber technique, was inhibited in a dose-dependent manner. The degree of
      inhibition varied from 15% with the lowest concentration of nicotine (50 ng/ml),
      to almost 90% with the highest (5 microg/ml). The results show that nicotine can
      have direct adverse effects on various functions of the periodontal cells.

PMID- 9923512
TI  - Reconstruction of anatomically complicated periodontal defects using a
      bioresorbable GTR barrier supported by bone mineral. A 6-month follow-up study of
      6 cases.
AB  - 6 anatomically complicated periodontal intrabony defects in 6 patients were
      surgically reconstructed using a bioresorbable GTR barrier supported by
      cancellous bovine bone mineral. Following cause-related periodontal treatment,
      open-flap surgery was performed to expose the defects. After debridement, the
      defects were filled with the bone mineral and covered with the barrier. All
      patients were advised to rinse 2 x daily with an 0.2% chlorhexidine digluconate
      solution and to avoid brushing in the operated area for 6 weeks. The treatment
      results were evaluated clinically and radiographically 6 months after surgery.
      All defects healed uneventfully and all patients maintained a high standard of
      plaque control throughout the study. Probing assessments during surgery showed a
      bone defect depth and width of on average 7.2 and 2.8 mm. The corresponding
      measures on presurgical intra-oral radiographs were 7.9 and 2.6 mm, respectively.
      Clinical attachment level (CAL) gain averaged 5.3 mm, corresponding to 73% of the
      original bone defect depth. Radiographically, the defect fill averaged 6.2 mm or
      80% of the original radiographic bone defect. It was concluded that the placement
      of bovine bone mineral beneath bioresorbable GTR barriers facilitates the
      clinical handling of the barrier and enhances the space for potential periodontal
      reconstruction of anatomically complicated defects. It remains, however, to be
      ascertained to what degree the achieved clinical and radiographic results reflect
      a gain in new connective tissue attachment and alveolar bone.

PMID- 9923513
TI  - Failure of mass antibiotic prophylaxis to control a prolonged outbreak of
      meningococcal disease in an Israeli village.
AB  - In January 1994 mass antibiotic prophylaxis was undertaken in the contiguous
      villages of Deir el-Asad and B'ine in northern Israel (combined population of
      11600) in response to a prolonged outbreak of serogroup B meningococcal infection
      with an overall annual rate of 37.4 cases of infection per 100000 residents. The
      average case fatality rate in the villages was 23% compared with 11% in Israel
      during the same period. Neisseria meningitidis group B was identified in 9 of 13
      (69%) cases. Seven of these were subtype P1.7,16. The persistence of the outbreak
      with its accompanying public reaction prompted the establishment of an
      intervention programme that included antibiotic prophylaxis for the whole
      community with monitoring for pharyngeal carriage of meningococci in a stratified
      sample of the population. The objectives were to achieve a reduction of carriage
      of the outbreak strain and to reduce morbidity and mortality. A total of 1036
      pharyngeal swabs were taken 1 day before and 6 weeks after treatment. Antibiotic
      prophylaxis was administered in one dose: children under 5-years-old received
      ceftriaxone i.m.; all others received oral ciprofloxacin. Overall, 96% of the
      population received treatment. The carriage rate was 8.3% prior to treatment
      (three serogroup B:14:P1.7,16), and 1.3% afterwards (one serogroup B:14:P1.7,16).
      The intervention failed to eradicate carriage of the putative outbreak strain, or
      to reduce the incidence and fatality rates in the villages. The outbreak finally
      terminated in late 1996. Public health professionals should bear this experience
      in mind when faced with prolonged, localized, nonexplosive outbreaks of
      meningococcal disease associated with low carriage rates of the outbreak strain.

PMID- 9923514
TI  - Antibacterial activity of meropenem against Pseudomonas aeruginosa, including
      antibiotic-induced morphological changes and endotoxin-liberating effects.
AB  - The in vitro effects of meropenem on Pseudomonas aeruginosa were examined by
      studying (i) the inhibitory and bactericidal concentrations of meropenem versus
      those of imipenem for clinical isolates; (ii) changes in bacterial morphology
      during in vitro culture; and (iii) release of endotoxin induced by meropenem
      compared with that induced by other antipseudomonal compounds. Meropenem MIC90
      and MBC90 values for 108 clinical isolates were 2 and 4.8 mg/l compared to 4.5
      and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and
      scanning electron microscopy showed that meropenem induced the formation of
      indeterminate bacterial cell forms at drug concentrations of 1-2.5 mg/l (0.5- to
      1.25-fold the MIC), while spheroplasts predominated at drug levels exceeding 5
      mg/l (2.5-fold the MIC). Determination of free and EDTA-releasable endotoxin
      activity by means of the Limulus lysate test showed that both meropenem and
      imipenem liberated significantly less endotoxin than did ceftazidime. Therefore,
      although meropenem binds to penicillin-binding proteins (PBPs) 2 and 3 (in
      contrast to imipenem, which binds to PBP2 only), endotoxin release should not be
      a cause of concern when treating systemic gram-negative infections with this
      drug.

PMID- 9923515
TI  - Strain-specific differences in the amount of Shiga toxin released from
      enterohemorrhagic Escherichia coli O157 following exposure to subinhibitory
      concentrations of antimicrobial agents.
AB  - There is no consensus regarding the benefit versus harm of antibiotic therapy for
      treatment of disease due to enterohemorrhagic Escherichia coli O157. The effects
      in vitro of subinhibitory concentrations of 13 antimicrobial agents on the
      release of Shiga toxin (Stx) by three different Escherichia coli O157 strains
      expressing Stx 1 or Stx 2 either alone or in combination were investigated. The
      Stx-induced cell death of Vero cells was determined using a colorimetric assay
      based on the measurement of lactate dehydrogenase (LDH) released into the
      supernatant from the cytosol of damaged cells. Growth of all O157 strains in
      broth cultures containing subinhibitory concentrations of cotrimoxazole,
      trimethoprim, azithromycin, or gentamicin was accompanied by a marked increase in
      the release of Stx. Exposure to cefixime, ceftriaxone, or erythromycin caused a
      marked increase in the release of Stx by the O157 strain producing Stx 2 alone,
      but decreased toxin production was observed with the Stx 1 producer and the
      strain producing Stx 1 and Stx 2. Exposure to ampicillin caused increased Stx
      release in the Stx 2-producing strain but had no effect on Stx production in the
      other two test isolates. Exposure to penicillin G, streptomycin, ciprofloxacin,
      fosfomycin, or sulfamethoxazole caused an increase in toxin production in two of
      the three test strains in each case, while decreases were observed for the other
      isolates. The response of Escherichia coli O157 isolates to subinhibitory
      concentrations of antibiotics seems to be highly dependent on the nature of the
      strain involved.

PMID- 9923516
TI  - Comparison of the ligase chain reaction with solid and liquid culture media for
      routine detection of Mycobacterium tuberculosis in nonrespiratory specimens.
AB  - The aim of this study was to compare the results of a commercial assay based on
      the ligase chain reaction [(LCR) LCx Probe System MTB; Abbott, USA] with those of
      culture in liquid medium (Septi-Chek AFB; Becton-Dickinson, USA) and culture on
      the egg-based Lowenstein-Jensen solid medium for the direct detection of
      Mycobacterium tuberculosis complex in nonrespiratory specimens. The results were
      analyzed according to the standard definition of a true-positive result. Two
      hundred thirty-five nonrespiratory samples routinely submitted to rule out
      tuberculosis were analyzed. All samples were smear-negative. Mycobacterial growth
      in either culture medium was detected in 18 (7.6%) specimens: Mycobacterium
      tuberculosis was recovered from seven (38.9%) specimens cultured on Lowenstein
      Jensen medium and from 18 (100%) specimens cultured in Septi-Chek AFB. The LCR
      protocol was positive in 22 specimens. None of the LCR-negative controls showed
      positive results. All samples positive by culture on Lowenstein-Jensen medium
      were positive by culture in liquid medium and by the LCR assay. However,
      Mycobacterium tuberculosis was detected by culture in liquid medium in two
      specimens that were negative by the LCR assay, whereas six specimens negative by
      culture in liquid medium were positive by the LCR protocol; three of these were
      identified as true-positive results of the LCR assay. The sensitivity,
      specificity, and positive and negative predictive values were 33.3%, 100%, 100%,
      and 93.8%, respectively, for Lowenstein-Jensen medium; 85.7%, 100%, 100%, and
      98.6% for the liquid medium; and 90.4%, 98.5%, 86.3%, and 99% for the LCR assay.
      These findings indicate that the LCR assay may be a valid method of high
      diagnostic yield for direct detection of Mycobacterium tuberculosis complex in
      nonrespiratory specimens.

PMID- 9923517
TI  - Comparison of a nonradiometric system with Bactec 12B and culture on egg-based
      media for recovery of mycobacteria from clinical specimens.
AB  - The MB/BacT (Organon-Teknika, USA) is a fully automated, rapid, nonradiometric
      system for the culture of mycobacteria from clinical samples. The rate of
      recovery of mycobacteria and the time to detection obtained with the MB/ BacT
      were compared with those obtained with Lowenstein-Jensen and Coletsos solid media
      and Bactec 7H12 (12B) (Becton-Dickinson, USA) broth when 600 processed specimens
      were inoculated into all media in parallel. Specimens included 383 respiratory
      samples, 20 urine samples, 23 purulent exudates, 13 stool samples, 103 blood
      samples, 14 bone marrow aspirates, and 44 body fluid samples or aspirates.
      Overall, 106 mycobacterial isolates comprising six species were recovered, of
      which 100 (94.3%) were detected with MB/BacT, 98 (92.5%) with egg-based media,
      and 96 (90.2%) with Bactec 12B. The recovery rates of Mycobacterium tuberculosis
      complex with MB/BacT, egg-based media, and Bactec 12B were 98.7%, 93.7, and
      89.9%, respectively. The average number of days to detection of single
      mycobacterial isolates was 14.2 days for MB/BacT, 26.1 days for egg-based media,
      and 11.7 days for Bactec 12B. The contamination rates were higher in MB/BacT (5%)
      than in Bactec 12B (1.8%) or egg-based media (1.5%). MB/BacT is a reliable,
      nonradiometric, less labor-intensive alternative to Bactec 12B for recovery of
      mycobacteria, but, as with other liquid culture methods, MB/BacT should be used
      in combination with a solid medium, not on its own.

PMID- 9923518
TI  - Comparison of virulence between clinical and environmental isolates of
      Aspergillus fumigatus.
AB  - Using a mixed infection model of murine invasive pulmonary aspergillosis, the
      comparative virulence of three clinical and four environmental isolates of
      Aspergillus fumigatus was investigated after intranasal inoculation. Coloured
      conidiospore mutants were first derived from clinical strains by ultraviolet
      mutagenesis and then compared with the parental strains and environmental
      strains. When the slight reductions in virulence associated with the spore colour
      mutations were taken into account, some environmental strains were shown to be
      less virulent than their corresponding clinical strains. It has yet to be
      determined whether these differences can account for the observation that many
      patients with invasive pulmonary aspergillosis appear to be infected with a
      single strain of Aspergillus fumigatus.

PMID- 9923519
TI  - Potential utility of recombinant human GM-CSF as adjunctive treatment of
      refractory oropharyngeal candidiasis in AIDS patients.
AB  - The aim of the study was to investigate the use of granulocyte macrophage-colony
      stimulating factor (GM-CSF) as an adjunctive treatment for clinically refractory
      mucosal candidiasis in patients with advanced AIDS. Three patients with advanced
      AIDS and oropharyngeal candidiasis clinically refractory to azoles or
      amphotericin B received GM-CSF for 14 days along with either fluconazole or
      amphotericin B. All three patients showed clinical improvement and mycological
      improvement without any adverse events. Thus, GM-CSF may be a possible
      alternative as adjunctive therapy in the management of refractory mucosal
      candidiasis in patients with advanced AIDS.

PMID- 9923520
TI  - False-positive tests for syphilis associated with human immunodeficiency virus
      and hepatitis B virus infection among intravenous drug abusers. Valencian Study
      Group on HIV Epidemiology.
AB  - The role of HIV, hepatitis C virus, and hepatitis B virus infections in the
      production of biological false-positive reactions for syphilis was evaluated in
      two large samples of intravenous drug abusers and homosexual men attending AIDS
      prevention centers in Spain. A significantly increased odds ratio (OR) for false
      positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76-2.83]
      was observed for HIV-seropositive intravenous drug abusers; biological false
      positive reactions were also more frequent (OR 1.73, 95% CI 1.30-2.31) among
      intravenous drug abusers who were hepatitis B virus seropositive but not among
      those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48-1.69). Among
      homosexuals, the association between HIV and biological false-positive reactions
      was restricted to subjects who were also intravenous drug abusers, indicating the
      crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers
      with a previous biological false-positive reaction yielded a false-positive
      result in their subsequent visit.

PMID- 9923521
TI  - Multicentre evaluation of a commercial test for the rapid diagnosis of
      Clostridium difficile-mediated antibiotic-associated diarrhoea.
AB  - An immunoassay for the detection of Clostridium difficile toxin A in stool
      samples (Clearview C. DIFF A; Unipath, UK) was evaluated against the cell
      cytotoxicity assay using 407 stool samples from patients suspected to have, or
      considered at risk of, antibiotic-associated diarrhoea. Of the samples tested, 98
      were positive and 280 were negative by both tests (sensitivity 83.1%, specificity
      96.9%). Following resolution of the 29 discrepant results, the sensitivity and
      specificity of the immunoassay were 91% and 98%, respectively, and the
      sensitivity for the cell cytotoxicity assay was calculated as 91.5%, with a
      specificity of 99%. The Clearview C. DIFF A test proved to be a rapid simple
      assay for the detection of Clostridium difficile toxin A in stool samples. The
      test was equally suited to single or batch testing, required minimal sample
      handling, and provided results within 30 min of applying the sample to the test
      unit.

PMID- 9923522
TI  - Evaluation of methods for isolation of Salmonella species using modified
      semisolid Rappaport-Vassiliadis medium and Salmonella-Shigella agar.
AB  - A total of 197 Salmonella strains were isolated from 1717 stool samples on
      salmonella-shigella agar and modified semisolid Rappaport-Vassiliadis medium
      before and after enrichment in selenite broth. Better sensitivity was obtained
      with salmonella-shigella agar than in direct plating (89.2% vs. 64.4%, P<0.0001)
      and after broth enrichment (96.4% vs. 88.1%, P<0.01). The incidence of false
      positive results using modified semisolid Rappaport-Vassiliadis medium was higher
      than that obtained using salmonella-shigella agar combined with the oxidase and
      C8 esterase tests in direct plating (33 vs. 2 strains) and after enrichment (43
      vs. 0 strains). Thus, based on its performance modified semisolid Rappaport
      Vassiliadis medium could be a suitable option for isolation of salmonellae from
      stool samples in clinical microbiology laboratories.

PMID- 9923523
TI  - Kinetics and toxicity of liposomal and conventional amikacin in a patient with
      multidrug-resistant tuberculosis.
AB  - The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for
      advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20
      mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly
      thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses.
      Accumulation occurred with alternate-day, but not weekly, dosing. The serum
      levels of amikacin obtained with the liposomal preparation were considerably
      greater than those obtained with the conventional preparation (range, 81-457 mg/l
      vs. 4.1-37.7 mg/l). The liposomal amikacin was well tolerated and led to clinical
      improvement, but it failed to achieve a microbiological response. The patient's
      sputum remained smear- and culture-positive during the treatment period with
      liposomal amikacin and for 9 months afterward.

PMID- 9923524
TI  - Treatment options for chronic prostatitis due to vancomycin-resistant
      Enterococcus faecium.
AB  - Prostatitis due to vancomycin-resistant enterococci has not been previously
      described. Reported here is a case of chronic prostatitis due to Enterococcus
      faecium, resistant to vancomycin, ampicillin, ciprofloxacin and doxycycline, in a
      42-year-old liver transplant recipient. Treatment with a combination of rifampin
      and nitrofurantoin for 6 weeks resulted in long-lasting cure. Other antimicrobial
      agents active in vitro against vancomycin-resistant enterococci, such as
      quinupristin/ dalfopristin and chloramphenicol, are unlikely to achieve
      sufficient prostatic tissue levels to be successfully utilized for treatment of
      this condition.

PMID- 9923525
TI  - Three cases of tuberculosis after heart transplantation in Spain.
AB  - Three cases are presented of tuberculosis occurring in a series of 410 heart
      transplant recipients in a Spanish hospital, representing a rate of 0.73%. Twenty
      eight cases reported in the literature are also reviewed. In most series
      reported, tuberculosis occurred in a small percentage of heart transplant
      recipients, the average rate being 1.25%. Compared to the general population, a
      higher percentage (28%) of extrapulmonary and disseminated forms of the disease
      is seen in these patients. Although a cure without recurrence can usually be
      achieved with a conventional anti-tuberculous antibiotic regimen, the disease is
      still associated with a significant mortality rate of 11%. Guidelines for the
      early diagnosis and treatment of these patients are discussed.

PMID- 9923526
TI  - Chorioamnionitis as an apparent source of vertical transmission of Staphylococcus
      cohnii and Ureaplasma urealyticum to a neonate.

PMID- 9923527
TI  - A case of Listeria murray/grayi bacteremia in a patient with advanced Hodgkin's
      disease.

PMID- 9923529
TI  - Treatment of pediatric patients with acute group A beta-hemolytic streptococcal
      tonsillopharyngitis.

PMID- 9923528
TI  - Acute pancreatitis as a complication of ritonavir therapy in a patient with AIDS.

PMID- 9923530
TI  - Mycobacterial lymphadenitis after initiation of highly active antiretroviral
      therapy.

PMID- 9923531
TI  - Genital ulcer in an AIDS patient with disseminated leishmaniasis.

PMID- 9923532
TI  - Neutralising antibody response to oral poliovirus vaccine after primary
      immunisation with inactivated poliovirus vaccine.

PMID- 9923533
TI  - Antistaphylococcal and antistreptococcal killing kinetics of ciprofloxacin,
      ofloxacin, sparfloxacin, and trovafloxacin.

PMID- 9923534
TI  - Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness
      of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in
      tumor-bearing mice.
AB  - PURPOSE: The pharmacokinetics (PK), biodistribution and therapeutic efficacy of
      cisplatin encapsulated in long-circulating pegylated (Stealth) liposomes (SPI
      077) were compared with those of nonliposomal cisplatin in two murine (C26 colon
      carcinoma and Lewis lung) tumor models. METHODS: In therapeutic effectiveness
      studies, mice bearing murine C26 or Lewis lung tumors received multiple
      intravenous doses of SPI-077 or cisplatin in a variety of treatment schedules and
      cumulative doses. In the PK and biodistribution study, mice received a single
      intravenous bolus injection of 3 mg/kg of either SPI-077 or cisplatin 14 days
      after inoculation with 10(6) C26 tumor cells. Plasma and tissues were analyzed
      for total platinum (Pt) content by graphite furnace (flameless) atomic absorption
      spectrophotometery (GF-AAS). RESULTS: Efficacy studies showed that SPI-077 had
      superior antitumor activity compared to the same cumulative dose of cisplatin.
      When lower doses of SPI-077 were compared to cisplatin at its maximally tolerated
      dose in Lewis lung tumors, equivalent SPI-077 antitumor activity was seen at only
      half the cisplatin dose. Higher cumulative doses of SPI-077 were well tolerated
      and had increased antitumor effect. SPI-077 PK were characterized by a one
      compartment model with nonlinear (saturable) elimination, whereas cisplatin PK
      were described by a two-compartment model with linear elimination. SPI-077 had a
      55-fold lower [corrected] volume of distribution, 3-fold higher peak plasma
      levels, and a 60-fold larger plasma AUC compared with cisplatin. In addition, SPI
      077-treated animals displayed a 4-fold reduction in Pt delivered to the kidneys
      (primary target organ of toxicity) relative to cisplatin, but a 28-fold higher
      tumor AUC than cisplatin. CONCLUSIONS: Based on the results of our studies,
      encapsulation of cisplatin in long-circulating pegylated liposomes has overcome
      limitations experienced with other liposomal cisplatin formulations. SPI-077 has
      a prolonged circulation time and increased tumor Pt disposition, and its
      antitumor effect is significantly improved compared to cisplatin in murine colon
      and lung cancer models.

PMID- 9923535
TI  - Epirubicin-containing high-dose chemotherapy followed by autologous hematopoietic
      progenitor cell transfusion for patients with chemotherapy-sensitive metastatic
      breast cancer: results of 5-year follow-up.
AB  - PURPOSE: Conventional chemotherapy for metastatic breast cancer results in very
      few long-term survivors. With a view to overcoming this problem, we hypothesized
      that a higher rate of complete response (CR) would lead to more long-term
      survivors. Therefore, we conducted a phase II study of epirubicin-containing high
      dose chemotherapy (HDC) followed by autologous hematopoietic progenitor cell
      transfusion in patients who were sensitive to induction chemotherapy. METHODS:
      The induction chemotherapy consisted of doxorubicin 60 mg/m2, cyclophosphamide
      750 mg/m2 and fluorouracil 750 mg/m2 on day 1. Supported by G-CSF, this
      chemotherapy was repeated for at least three cycles at intervals of 2 weeks until
      the achievement of > 50% tumor regression. The HDC comprised epirubicin 120 mg/m2
      on day 1, cyclophosphamide 60 mg/kg on days 1 to 3 and thiotepa 6 mg/kg on days 1
      to 3, followed by autologous bone marrow transplantation and peripheral blood
      stem cell transfusion. RESULTS: Of 25 patients who achieved a partial response to
      the induction chemotherapy, 17 were treated with the HDC. Of the 15 patients
      evaluable for response, 10 achieved a CR (67%), giving an overall CR rate of 43%
      (10/25). The disease-free survival rate at 5 years was 27%. The median duration
      of overall survival was 21 months and the overall survival rate at 5 years was
      31%. However, the survival curves were not significantly different from those of
      the historical controls who achieved a CR or PR to conventional chemotherapy.
      There were three early deaths, one as a consequence of disease progression and
      two treatment-related (sepsis and heart failure). Diarrhea (grade 3, 76%) and
      stomatitis (grade 3-4, 29%) were the dose-limiting toxicities. CONCLUSIONS: The
      present study suggests that epirubicin-containing HDC is able to induce a high
      rate of CR, but its benefit in terms of survival is still unclear. To determine
      whether HDC can achieve a cure in some patients, further studies in a larger
      number of patients, with a longer follow-up, are necessary.

PMID- 9923536
TI  - Inhibition of paclitaxel elimination in the isolated perfused rat liver by
      Cremophor EL.
AB  - PURPOSE: Cremophor can alter the pharmacokinetics of cytotoxic drugs, including
      doxorubicin and etoposide. In view of its presence in the formulation of
      paclitaxel, the aim of this study was to investigate the influence of Cremophor
      on the hepatobiliary elimination of paclitaxel. METHODS: In a recirculating
      isolated perfused rat-liver system the elimination of 1.7 mg paclitaxel given as
      a bolus into the perfusate reservoir was monitored in perfusate and bile in
      controls and after the administration of either 80 or 800 microl Cremophor. The
      higher dose of Cremophor yields clinically relevant perfusate concentrations.
      Paclitaxel was measured in perfusate, bile, and liver tissue by high-performance
      liquid chromatography. RESULTS: Cremophor caused a dose-dependent inhibition of
      the elimination of paclitaxel, with a statistically significant mean value +/-SD,
      n=3; (P < 0.05 versus controls Bonferroni t-test) 9-fold increase in AUC (2227+/
      106 versus 245+/-40 microg ml(-1) min), 9-fold decrease in total clearance (0.8+/
      0.1 versus 7.0+/-1.1 ml/min), and 5-fold increase in elimination half-life (92+/
      14 versus 18+/-4 min) being observed after a dose of 800 microl Cremophor. With
      the addition of Cremophor the amount of paclitaxel remaining after 3 h increased
      in perfusate from none to 20%, increased in liver tissue from 4% to 18%, and
      remained constant in bile at 11-13%. In the control group, 86% of the paclitaxel
      dose was recovered in bile as five putative metabolites, which were measured in
      paclitaxel equivalents, with the major metabolite. M3 co-eluting with 3'-p
      hydroxypaclitaxel. This decreased to 45% of the dose on the addition of
      Cremophor, and the ratio of M3 to paclitaxel in bile decreased. CONCLUSIONS:
      Cremophor inhibits the hepatic elimination of paclitaxel in the isolated perfused
      rat liver, primarily by preventing the drug from reaching sites of metabolism and
      excretion. The presence of Cremophor in the paclitaxel formulation may therefore
      contribute to the nonlinear pharmacokinetics and pharmacodynamics of paclitaxel.

PMID- 9923537
TI  - In vitro translation of a 2.3-kb splicing variant of the hamster pgp1 gene whose
      presence in transfectants is associated with decreased drug resistance.
AB  - PURPOSE: P-glycoprotein (P-gp), a product of the Chinese hamster pgpl gene,
      confers multidrug resistance to mammalian cells in which it is overexpressed
      either by transfection or as a result of drug selection. It is encoded by a 4.3
      kb mRNA and in its unglycosylated form has a predicted molecular weight of
      approximately 141 kDa. When a cDNA containing this sequence is transfected into
      drug-sensitive Chinese hamster lung cells and is expressed under the control of
      the beta-actin promoter, both the full-length 4.3-kb mRNA and a 2.3-kb transcript
      are produced. The latter results from a splicing event that utilizes near
      consensus 5' and 3' splicing signals resident in the full-length mRNA, and it has
      also been found to be present in cell lines that express the native gene.
      Therefore, it is a splicing product of pgpl per se. This report is concerned with
      the biological relevance of this transcript. METHODS: In vitro transcription and
      translation experiments were used to show that the putative open reading frame of
      the 2.3-kb transcript encodes a novel 57-kDa protein (p57pgp1) that contains
      transmembrane domains 9-12 and the C-terminal ATP binding fold of P-gp. To
      elucidate the function of p57pgp1, expression vectors containing cDNAs
      representing (1) the 2.3-kb transcript, (2) the full-length 4.3-kb mRNA, and (3)
      a splice-disabled 4.3-kb transcript in which production of the 2.3-kb transcript
      is eliminated by an in-frame mutation at the 3' splice site, were constructed and
      transfected into DC-3F cells. Additional expression vectors in which p57pgp1
      represented the N-terminus of a green fluorescent protein fusion construct were
      also prepared and used for transient expression studies. RESULTS: Overexpression
      of the 2.3-kb transcript alone did not confer multidrug resistance. Transfectants
      in which both the 4.3-kb transcript and the 2.3-kb transcript were present,
      compared with transfectants in which no 2.3-kb transcript was expressed, but in
      which the level of expression of the 4.3-kb mRNA alone was the same, showed
      little change in cross-resistance pattern. However, the overall level of
      resistance in the latter cells was increased by approximately twofold. Hence the
      presence of the 2.3-kb transcript was associated with a decrease in drug
      resistance. In vitro transcription and translation experiments and transient
      expression studies indicate that p57pgp1 can be expressed both in vitro and in
      vivo. CONCLUSION: These results demonstrate that a splicing variant of pgp1
      contains an open reading frame capable of translation in vitro and in vivo and
      suggest that alterations in splicing may contribute both directly and indirectly
      to the overall mechanism of pgp1-mediated multidrug resistance in CHL cells.

PMID- 9923538
TI  - Effect of Tween-80 on cell killing by etoposide in human lung adenocarcinoma
      cells.
AB  - PURPOSE: The non-ionic detergent Tween-80, a surface-active agent, has been shown
      to modulate the cytocidal effect of certain antitumor agents. In the present
      study, we sought to determine whether or not Tween-80 could enhance the antitumor
      effect of etoposide (VP16) in human lung cancer cells in vitro. METHODS: Survival
      fractions were measured by growth inhibiton assays of PC14, H69, KB, and
      PC14/CDDP (the corresponding cisplatin-resistant subline of PC14) cells. An in
      vitro clonogenic assay of PC14 and PC14/CDDP cells was undertaken after
      incubation for 10-12 days in RPMI-1640 medium with 20% fetal calf serum and 1.72%
      methyl cellulose, plus continuous exposure to VP16 with Tween-80. We also
      investigated the direct toxicity of Tween-80 to PC14 and PC14/CDDP cells using a
      clonal assay. The intracellular accumulation of VP16 was further analyzed using
      [3H]VP16 in PC14, PC14/CDDP, A549, KB and H69 cells, and compared with that of
      daunorubicin (DNR), a hydrophilic anti-cancer agent, using [3H]DNR in PC14, A549
      and KB cells. RESULTS: It was found that PC14/CDDP had collateral sensitivity to
      VP16 and Tween-80 markedly enhanced the killing effect of VP16 not only of PC14
      cells but also of PC14/CDDP cells while exerting little cytotoxic effect.
      Moreover, Tween-80 increased the intracellular accumulation of VP16 in PC14,
      PC14/CDDP and A549 cells, and not in KB and H69 cells. Tween-80 did not increase
      the intracellular DNR levels in PC14, A549 and KB cells. CONCLUSIONS: Tween-80
      was shown to potentiate the cytotoxicity of VP16 against several human lung
      adenocarcinoma cells by increasing the accumulation of VP16 in vitro. Tween-80
      mediated sensitization of lung adenocarcinoma cells to VP16 is considered to be
      related to both the characteristics of the cell membrane in adenocarcinoma cells
      and the lipotropic properties of VP16. These results suggest that this
      combination might have the potential to improve the therapeutic index of VP16 in
      human lung adenocarcinoma.

PMID- 9923539
TI  - Pharmacokinetics of melphalan in isolated limb perfusion.
AB  - The pharmacokinetics of melphalan was studied by sampling of tissue and plasma in
      72 rats that underwent isolated hyperthermic limb perfusion under different
      conditions. A miniaturized extracorporeal circulation system for small animals
      was used for perfusion of the rat hindlimb. Melphalan levels (L-phenylalanine
      mustard, L-PAM) were determined by high-performance liquid chromatography (HPLC).
      The temperature of the perfusate plasma and tissue, pH, administration method,
      and flow rate were modified and compared with regard to their influence on
      pharmacokinetic parameters. The highest tissue penetration of melphalan was
      observed under the following conditions: (a) pH range of the perfusate plasma
      between 7.3 and 7.7 (physiological environment), (b) temperature range of the
      perfusate from 40 degrees to 41.5 degrees C (destruction of cellular carrier
      systems at higher temperatures and increased inactivation by hydrolysis of
      melphalan above 41.5 degrees C), (c) application of melphalan as a single dose
      into the reservoir of the extracorporeal circuit (optimal tissue penetration),
      and (d) reduced perfusate flow (prolonged contact time between perfusate and
      tissue).

PMID- 9923540
TI  - The p53 tumor suppressor gene in anticancer agent-induced apoptosis and
      chemosensitivity of human gastrointestinal cancer cell lines.
AB  - PURPOSE: While the target of many anticancer agents has been identified, the
      processes leading to killing of the cancer cells and the molecular basis of
      resistance to the drugs are not well understood. We used human gastrointestinal
      cancer cell lines and examined how anticancer agents induced cell killing and how
      the chemosensitivity of these lines was determined. METHODS: Twelve
      gastrointestinal cancer cell lines were examined for the presence of either a
      wild-type or mutant p53 gene by direct sequencing. We also determined whether or
      not cell killing would occur when the cell lines were exposed to anticancer
      drugs. The sensitivity to the anticancer agents was determined based on colony
      formation. RESULTS: All 12 gastrointestinal cancer cell lines carried either a
      wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the
      wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were
      exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil
      (5-FU), cell death ensued. In these cells, the population of cells in G1 phase
      increased after exposure to high-dose anticancer agents, but cells in G2 phase
      increased when exposed to low-dose anticancer agents. Our observations support
      the concept that cells carrying the wild-type p53 gene tend to be sensitive to
      etoposide and DXR and, in particular, deletion of the p53 function results in a
      greater resistance to anticancer agents. CONCLUSION: Based on our findings, human
      gastrointestinal cancer-related cell death apparently occurs via a p53-dependent
      pathway. A relationship was observed between the induction of cell death and
      chemosensitivity.

PMID- 9923541
TI  - Effects of SCH 59228, an orally bioavailable farnesyl protein transferase
      inhibitor, on the growth of oncogene-transformed fibroblasts and a human colon
      carcinoma xenograft in nude mice.
AB  - The products of the Ha-, Ki-, and N-ras proto-oncogenes comprise a family of 21
      kDa guanine nucleotide-binding proteins which play a crucial role in growth
      factor signal transduction and in the control of cellular proliferation and
      differentiation. Activating mutations in the ras oncogenes occur in a wide
      variety of human tumors. Ras proteins undergo a series of posttranslational
      processing events. The first modification is addition of the 15-carbon isoprene,
      farnesyl, to a Cys residue near the carboxy-terminus of Ras. Prenylation allows
      the Ras oncoprotein to localize to the plasma membrane where it can initiate
      downstream signalling events leading to cellular transformation. Inhibitors of
      the enzyme which catalyzes this step, farnesyl protein transferase (FPT), are a
      potential class of novel anticancer drugs which interfere with Ras function. SCH
      59228 is a tricyclic FPT inhibitor which inhibits the farnesylation of purified
      Ha-Ras with an IC50 of 95 nM and blocks the processing of Ha-Ras in Cos cells
      with an IC50 of 0.6 microM. SCH 59228 has favorable pharmacokinetic properties
      upon oral dosing in nude mice. The in vivo efficacy of SCH 59228 was evaluated
      using a panel of tumor models grown in nude mice. These included several rodent
      fibroblast lines expressing mutationally-activated (val12) forms of the Ha-Ras
      oncogene. In some cases, these proteins contain their native C-terminal sequence
      (CVLS) which directs farnesylation. In one model, the C-terminal sequence was
      altered to CVLL, making the expressed protein a substrate for a distinct prenyl
      transferase, geranylgeranyl protein transferase-1. When dosed orally at 10 and 50
      mg/kg (four times a day, 7 days a week) SCH 59228 significantly inhibited tumor
      growth of cells expressing farnesylated Ha-Ras in a dose-dependent manner; over
      90% growth inhibition was observed at the 50 mg/kg dose. Tumor growth of cells
      expressing the geranylgeranylated form of Ha-Ras was less potently inhibited.
      Growth of tumors derived from a rodent fibroblast line expressing activated Ki
      Ras containing its native C-terminal sequence (CVIM), which preferentially
      directs farnesylation, was also inhibited by SCH 59228. Inhibition in the Ki-Ras
      model was less than that observed in the Ha-Ras model. In contrast, tumors
      derived from cells transformed with the mos oncogene were not significantly
      inhibited even at the highest dose level. SCH 59228 also significantly and dose
      dependently inhibited the growth of human colon adenocarcinoma DLD-1 xenografts
      (which express activated Ki-ras). These results indicate that SCH 59228 possesses
      in vivo antitumor activity upon oral dosing in tumor models expressing activated
      ras oncogenes. This is the first report of oral antitumor activity with an FPT
      inhibitor. These results are discussed in light of recent observations on
      alternative prenylation of some Ras isoforms.

PMID- 9923542
TI  - Use of V79 cells with stably transfected cytochrome P450 cDNAs in studying the
      metabolism and effects of cytotoxic drugs.
AB  - PURPOSE: Studying the metabolism of cytotoxic drugs has become increasingly
      necessary to predict clinically significant drug-drug interactions and to
      understand the basis of interindividual variations in the pharmacokinetics of
      anticancer agents. The aim of this study was to determine the feasibility of
      using V79 Chinese hamster fibroblasts, which are stably transfected with
      cytochrome P450 (CYP) cDNAs, to study the metabolism of cytotoxic drugs in vitro.
      METHODS: The 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT)
      assay was used to determine cell survival after incubation with drugs. Gas
      chromatography/mass spectroscopy was used for the quantitation of metabolites of
      cyclophosphamide and ifosfamide in culture medium. The coculture technique was
      used to study the generation of cytotoxic metabolites in culture medium. RESULTS:
      After treatment with either cyclophosphamide or ifosfamide (100 microM to 1 mM)
      cytotoxicity was demonstrated in only cytochrome CYP2B1- and cytochrome CYP3A4
      expressing cells. Treatment of parental nontransfected cells that were cocultured
      with CYP-expressing cells with cyclophosphamide resulted in increased sensitivity
      to this drug. All active and inactive metabolites of cyclophosphamide and
      ifosfamide were detected in the culture medium. Cyclophosphamide-induced
      cytotoxicity in CYP2B1- and CYP3A4-expressing cells was abrogated by metyrapone
      and midazolam/ troleandomycin, respectively. Paclitaxel showed greater
      cytotoxicity against parental V79 cells than against the CYP2BI-, 2E1-, or 3A4
      expressing cells, which was also influenced by cotreatment with CYP inhibitors.
      CONCLUSIONS: Stable expression of CYP cDNAs by V79 cells provided an in vitro
      system to study cytotoxic drug metabolism. Cell viability and metabolite assays
      were used to determine the differential metabolism and effects in different CYP
      transfected cell lines treated with cytotoxic drugs. The potential use of this
      V79 cell expression system is in studying enzymes involved in the metabolism of
      cytotoxic drugs, especially early in drug development. In addition, this system
      may be used to determine drug interactions that may influence the outcome of
      therapy in patients with cancer.

PMID- 9923543
TI  - Inability to escalate vinorelbine dose intensity using a daily x3 schedule with
      and without filgrastim in patients with metastatic breast cancer.
AB  - PURPOSE: Vinorelbine (Navelbine) is a semi-synthetic vinca alkaloid with
      documented activity in breast cancer. The major dose-limiting toxicity (DLT) when
      given weekly is myelosuppression with minimal neurologic toxicity. This phase I
      study attempted to define the maximally tolerated dose (MTD) and the DLT of
      vinorelbine on a daily x3 schedule with and without filgrastim support. METHODS:
      A total of 19 patients with stage IV breast cancer were enrolled in separate
      studies at Duke University Medical Center (DUMC) and the Dana-Farber Cancer
      Institute (DFCI). Eligible patients could have received up to two prior
      chemotherapy regimens in the metastatic setting and had to have an ANC >
      1500/mm2, PLT > 100000 m3, creatinine < 2.0 mg/dl, bilirubin < 2.0 mg/dL, SGOT
      not more than three times normal, and performance status 0-1. Vinorelbine was
      administered using a daily x3 schedule every 3 weeks. The protocols were designed
      to study dose escalation with and without growth factor support. At DUMC, in the
      initial phase of the study, the starting dose was 15 mg/m2 per day and dose
      escalations of 5 mg/m2 were planned until DLT developed and the MTD was defined.
      DLT was defined as granulocytopenia < 500/mm3 for > 7 days, grade IV
      thrombocytopenia, febrile neutropenia, or grade III or greater nonhematologic
      toxicity. In the second phase of the study, growth factor support was given with
      vinorelbine at the MTD. Filgrastim at a dose of 5 microg/kg was started on day 4
      of the 21-day cycle and was continued until the neutrophil count exceeded 10000
      cells/ mm3. At DFCI, all patients received growth factor starting on day 4 and
      the starting dose of vinorelbine was 25 mg/m2. RESULTS: At DUMC, DLT was seen at
      20 mg/m2 in three of three patients and included febrile neutropenia, grade IV
      neutropenia > 7 days, grade III neurotoxicity, and grade III vomiting. Despite
      the addition of filgrastim, DLT was again seen at 20 mg/m2 and included grade III
      neurotoxicity (jaw pain, abdominal pain, constipation, ileus) and grade IV
      mucositis. Three patients at DFCI were treated with vinorelbine at a dose of 25
      mg/m2 with growth factor support, and two developed DLT including febrile
      neutropenia, neutropenia > 7 days, and grade III stomatitis. CONCLUSIONS: Our
      effort to escalate the dose intensity of vinorelbine on this schedule was not
      successful and was complicated by hematologic and nonhematologic toxicity. A
      daily x3 schedule of vinorelbine should not be pursued as an alternative
      treatment regimen in patients with previously treated metastatic breast cancer.

PMID- 9923544
TI  - Multiple DNA repair mechanisms and alkylator resistance in the human
      medulloblastoma cell line D-283 Med (4-HCR).
AB  - PURPOSE: We have previously reported preferential repair of DNA interstrand
      crosslinks in the 4-hydroperoxycyclophosphamide-resistant human medulloblastoma
      cell line D-283 Med (4-HCR). We now report further studies that explored the
      potential mechanisms underlying this repair. METHODS: Limiting dilution assays
      and Western, Southern, and Northern blots were used to compare specific
      differences between D-283 Med (4-HCR) and its parental line D-283 Med. RESULTS: D
      283 Med (4-HCR) was cross-resistant to melphalan and 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU), with O6-alkylguanine-DNA alkyltransferase (AGT) levels of
      466+/-164 fmol/mg protein; AGT levels in the parental line, D-283 Med, were 76+/
      96 fmol/mg. The increase in AGT activity was not a result of gene amplification.
      Depleting AGT with O6-benzylguanine partially restored sensitivity to BCNU. Both
      cell lines were deficient in the human mismatch protein MutLalpha. ERCC4 mRNA and
      poly(ADP-ribose) polymerase levels were similar in both cell lines, and ERCC1
      mRNA levels were 2- to 2.5-fold lower in D-283 Med (4-HCR). Topoisomerase I
      levels were 2- to 2.5-fold higher in D-283 Med compared with D-283 Med (4-HCR).
      CONCLUSION: These results, while illustrating the multiple differences between D
      283 Med and D-283 Med (4-HCR), do not explain the enhanced DNA interstrand
      crosslink repair seen in D-283 Med (4-HCR).

PMID- 9923545
TI  - Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkyltransferase.
AB  - PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant
      to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA
      interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells
      are cross-resistant to 1,3-bis(2-chloroethyl)- -nitrosourea, but partial
      sensitivity is restored after elevated levels of O6-alkylguanine-DNA
      alkyltransferase (AGT) are depleted by O6-benzylguanine (O6-BG). Studies were
      conducted to define the activity of 4-HC and 4
      hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) after AGT is
      depleted by O6-BG. METHODS: Limiting dilution and xenograft studies were
      conducted to define the activity of 4-HC and 4
      hydroperoxydidechlorocyclophosphamide with or without O6-BG. RESULTS: The
      activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4
      HCR) was increased after AGT depletion by O6-BG preincubation. Similar studies
      with Chinese hamster ovary cells, with or without stable transfection with a
      plasmid expressing the human AGT protein, revealed that the AGT-expressing cells
      were significantly less sensitive to 4-HC and 4
      hydroperoxydidechlorocyclophosphamide. Reaction of DNA with 4-HC, phosphoramide
      mustard, or acrolein revealed that only 4-HC and acrolein caused a decrease in
      AGT levels. CONCLUSIONS: We propose that a small but potentially significant part
      of the cellular toxicity of cyclophosphamide in these cells is due to acrolein,
      and that this toxicity is abrogated by removal of the acrolein adduct from DNA by
      AGT.

PMID- 9923546
TI  - Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte
      colony-stimulating factor (GCSF) support in patients with metastatic breast
      cancer and limited prior therapy.
AB  - PURPOSE: Early phase II evaluation of intravenous bolus mitoxantrone indicated
      objective response rates of 17 36% in patients with metastatic breast cancer.
      Subsequently, it has been suggested that continuous infusion may be the optimal
      way to administer this drug in order to achieve maximal cytotoxic effect with
      minimal toxicity. We present the results of a phase II study that evaluated the
      efficacy and side effects of mitoxantrone administered at the maximally tolerated
      dose by continuous infusion in patients with metastatic breast cancer. METHODS:
      This study included 16 patients with metastatic breast cancer and limited
      previous therapy for their metastatic disease. Mitoxantrone, 1.5 mg/m2 per day,
      was given by continuous intravenous infusion for 14 consecutive days repeated
      every 21 days with concomitant granulocyte colony-stimulating factor support.
      Dose escalation was allowed. RESULTS: No complete tumor response was seen. Two
      patients (13%, CI 0-29%) had a partial response, nine patients (56%) had
      progressive disease and the remaining five patients (31%) had stable disease on
      therapy. The major dose-limiting side effect was myelotoxicity. Two of the 16
      patients (13%) experienced asymptomatic cardiotoxicity that required
      discontinuation of therapy. CONCLUSIONS: Our results indicate limited antitumor
      activity and significant toxicity of mitoxantrone given by continuous infusion as
      second-line chemotherapy for metastatic breast cancer. The objective response
      rate documented in this study is inferior to response rates reported with other
      second-line regimens, particularly the taxanes, now available for this patient
      population.

PMID- 9923547
TI  - Pharmacokinetics of paclitaxel in an anephric patient.
AB  - PURPOSE: To assess the pharmacokinetics of paclitaxel for recurrent Wilms' tumor
      in an anephric pediatric patient receiving hemodialysis. METHODS: Paclitaxel was
      administered at a dose of 250 mg/m2 and 350 mg/m2 by 24-h continuous intravenous
      (IV) infusion as two consecutive courses, respectively, separated by
      approximately 3 weeks. Paclitaxel plasma concentrations were measured by high
      performance liquid chromatography (HPLC). RESULTS: Paclitaxel disposition was
      comparable to that reported in similarly treated children with normal renal
      function. For the first course (250 mg/ m2), paclitaxel concentrations were best
      fit by a two-compartment, first-order model. The calculated pharmacokinetic
      parameters were 0.312 h(-1) for the first-order rate constant of elimination
      (Ke), 52.4 l/m2 for the apparent volume of distribution (Vc), 0.170 h(-1) and
      0.105 h(-1) for the first-order rate constants for transit from central to
      peripheral compartments (Kcp) and peripheral to central compartments (Kpc),
      respectively, 16.9 microM x h for the area under the plasma concentration-versus
      time curve (AUC), and 273 ml/min per m2 for average clearance (Cl). The
      concentration-versus-time data with the second course (at the higher dosage of
      350 mg/m2) were better described by a two-compartment model with saturable
      elimination. The calculated pharmacokinetic parameters were 12.0 micromol x h(-1)
      for the maximal rate of elimination (Vm1-0), 0.158 microM for the concentration
      at which the rate of elimination is 50% of maximal (Km1-0), 0.809 h(-1) for Kcp,
      0.0792 h(-1) for Kpc, 23.5 l/m2 for Vc, 20.9 microM x h for AUC, and 327 ml/min
      per m2 for Cl. Paclitaxel was undetectable in the dialysate. CONCLUSIONS: The
      level of systemic exposure in our anephric patient was comparable to or lower
      than that achieved in patients with normal renal function at similar dosages. The
      patient tolerated therapy without problems. It appears that pediatric patients in
      renal failure can be treated with paclitaxel as a 24-h continuous infusion at
      doses similar to those used in patients with normal renal function.

PMID- 9923548
TI  - Antitumor activity, distribution, and metabolism of 13-cis-retinoic acid as a
      single agent or in combination with tamoxifen in established human MCF-7
      xenografts in mice.
AB  - PURPOSE: The efficacy of 13-cis-retinoic acid (13-CRA) given as a single agent or
      in combination with tamoxifen (TAM) was determined in athymic nude mice bearing
      advanced s.c. MCF-7 human breast cancers. METHODS: 13-CRA alone was given by
      gavage at doses ranging from 26.4 to 200 mg/kg. TAM alone was given by gavage at
      doses of 7.5, 15, 30, or 60 mg/kg. For combination studies, each dose of TAM was
      followed 4 h later by 13-CRA at doses of 25, 50, 100, or 200 mg/kg. All
      treatments began on day 12 and were continued for 3 weeks. RESULTS: The median
      time to two doublings recorded for the control and for 13-CRA and TAM given as
      single agents at the highest dose were 22.2, 29.2, and 54.7 days, respectively.
      In combination, 100 and 200 mg/kg 13-CRA with 7.5 mg/kg TAM resulted in a delay
      in tumor growth at least as high as that achieved with highest-dose TAM alone,
      but the effect was not synergistic. Pharmacokinetic analysis of 13-CRA was
      performed in plasma, liver, and tumor from mice bearing 0.5- to 2.0 g carcinomas
      following a single dose of 100 mg/kg 13-CRA. Results showed that 13-CRA was
      metabolized differently in various tissues, but concentrations of 13-CRA detected
      in tumor were in the range reported to be active in vitro. all-trans-Retinoic
      acid (ATRA) concentrations were about 5% of the 13-CRA concentrations detected in
      plasma, 68% of those found in liver, and 20% of those found in tumor. 4-oxo-CRA
      represented between 2% and 10% of 13-CRA concentrations detected in plasma and
      liver but was not detected in tumor. Furthermore there was no difference in peak
      plasma 13-CRA concentrations found in the same tissues at 30 min after a single
      dose or after the eighth dose of 100 mg/kg 13-CRA or 13-CRA and TAM. Mean 13-CRA
      concentrations detected in liver and tumor were 50-90% and 16-30% of plasma peak
      concentrations, respectively. No difference in 4-oxo-CRA concentration was
      observed between the treatment groups. CONCLUSIONS: These data suggest that 13
      CRA is not effective against established human breast tumor xenografts despite
      the stability of the pharmacokinetics of 13-CRA and the generation of ATRA as a
      metabolite. The addition of 13-CRA to TAM did not improve the efficacy of TAM
      against these estrogen-receptor-positive xenografts.

PMID- 9923549
TI  - Efficacy of suramin against human prostate carcinoma DU145 xenografts in nude
      mice.
AB  - PURPOSE: Toward developing a model to study the mechanism of action of suramin
      against prostate cancer, we identified the effect of suramin on the growth of
      xenografts of the androgen-independent human prostate carcinoma DU145 cell line
      and our subline of suramin-resistant (SR) DU145 cells which are less responsive
      to suramin in vitro. METHODS: Athymic nude mice bearing DU145 or SR DU145
      xenografts were treated intraperitoneally (IP) once weekly with normal saline
      (vehicle control) or suramin in normal saline. For data analysis mice were
      grouped as follows: 0 mg/kg (controls), < 210 mg/kg, 210 to 260 mg/kg, or >260
      mg/kg suramin. RESULTS: The growth of DU 145 xenografts was slowed by treatment
      with 210 to 260 mg/kg suramin IP once weekly: differences in tumor volume for the
      210 to 260 mg/kg group compared with the control group on days 29 and 57 showed
      growth inhibited by 43% and 55%, respectively. At the same time, growth of SR DU
      145 xenografts generally was not slowed by suramin treatment at any dose, but
      appeared to be enhanced to some degree by all doses of suramin during the typical
      slower initial growth phase of xenografts of this cell line: differences in tumor
      volume compared with control on day 29 showed growth enhanced by 100% to 342%.
      Mice treated with 210 to 260 mg/kg maintained nadir suramin plasma levels near
      our clinically relevant target of 1 x 10(-4) M. CONCLUSIONS: Suramin, without
      concomitant corticosteroid therapy, was effective in slowing the growth of DU145
      xenografts in nude mice at clinically relevant plasma suramin levels. The data
      showing efficacy for DU145 xenografts was supported by the lack of efficacy at
      the same time for xenografts of cells known to be less responsive to suramin in
      vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels.
      In discussions on the utility of suramin our data should be considered as support
      for continuing the study of suramin in the treatment of advanced, androgen
      independent prostate cancer.

PMID- 9923550
TI  - Inhibitory effect of suramin in rat models of angiogenesis in vitro and in vivo.
AB  - The aim of the present study was to test the ability of the chemotherapeutic
      agent suramin to inhibit angiogenesis in experimental models in vitro and in
      vivo. In the culture of rat aortic rings on fibronectin, suramin dose-dependently
      inhibited vascular cell growth, achieving the maximal effect (mean - 88% versus
      controls, P < 0.05) at 400 microg/ml. Image analysis showed that suramin could
      inhibit microvessel sprouting in fibrin from rat aortic rings as evaluated by the
      ratio between the cellular area and the mean gray value of the sample (sprouting
      index); suramin at 50 microg/ml significantly reduced the sprouting index from
      the control value of 0.35+/-0.04 to 0.14+/-0.02 mm2/gray level (P < 0.05).
      Likewise, the area occupied by cells was 19.2+/-1.8 mm2 as compared with 41.8+/
      4.2 mm2 in controls (P < 0.05). In the rat model of neovascularization induced in
      the cornea by chemical injury, suramin at 1.6 mg/eye per day reduced the length
      of blood vessels (0.7+/-0.1 mm as compared with 1.5+/-0.1 mm in controls, P <
      0.05). In the same model the ratio between the area of blood vessels and the
      total area of the cornea (area fraction score) was decreased by suramin from
      0.19+/-0.02 in controls to 0.03+/-0.003 (P < 0.05). Suramin given i.p. at 30 mg/
      kg per day markedly inhibited the neovascularization induced in the rat mesentery
      by compound 48/80 or conditioned medium from cells secreting the angiogenic
      protein fibroblast growth factor-3 (FGF-3). The area fraction score in control
      rats treated with compound 48/80 was 0.31+/-0.03, and this was reduced to 0.07+/
      0.01 by suramin (P < 0.05). After i.p. administration of FGF-3 the area fraction
      score was reduced by suramin from 0.29+/-0.03 to 0.05+/-0.01 (P < 0.05). These
      results provide evidence that suramin exerts inhibitory effects on angiogenesis
      in both in vitro and in vivo models.

PMID- 9923551
TI  - Measurement of delivery and metabolism of tirapazamine to tumour tissue using the
      multilayered cell culture model.
AB  - PURPOSE: Efficient extravascular penetration is essential for the optimal
      activity of most anticancer drugs and is particularly relevant to bioreductive
      cytotoxins which target hypoxic cells that can be located distal to functional
      blood vessels within tumours. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N
      oxide; Triazone; SR 259075; formerly SR 4233) is a lead bioreductive cytotoxin
      currently undergoing clinical evaluation. It exhibits preferential cytotoxicity
      towards cells at reduced oxygen tension, and could complement existing anticancer
      therapies where hypoxic cells are believed to constitute a refractory population.
      We assessed the ability of tirapazamine to penetrate tumour tissue using an in
      vitro multilayered cell culture (MCC) model. METHODS: Diffusion of tirapazamine
      through oxic and hypoxic multilayered cell cultures composed of SiHa. human
      cervical carcinoma cells, was measured using a dual reservoir diffusion apparatus
      from which samples were quantified via HPLC. Drug concentration kinetics from
      both reservoirs were analysed using a mathematical model for diffusion and
      metabolism within the MCC. Results were then applied to a second mathematical
      model which described extravascular drug penetration within a tumour cord, the
      sheath of cells surrounding a blood vessel. RESULTS: The diffusion coefficient of
      tirapazamine within SiHa MCCs was determined as 7.0+/-0.5 x 10(-7) cm2/s and the
      maximal metabolic rate for hypoxic MCCs, Vmax, as 1.5+/-0.4 microM/s. The
      thickness of individual tissue cultures was determined by diffusion of tritiated
      water (HTO). A linear relationship was shown to exist between tissue thickness
      and the inverse of permeability to HTO. Experimental results were used to
      simulate drug distribution within a tumour cord. These simulations indicate that,
      when tirapazamine is administered via intravenous infusion, a stable tirapazamine
      distribution throughout the cord occurs within 15 min with cells most peripheral
      to the blood vessel exposed to only 10% of the blood drug concentration. Under
      these conditions, the simulations predict cell kill to be limited to the first 75
      microm of tissue surrounding a blood vessel. CONCLUSION: This study indicates
      that extravascular penetration of tirapazamine to peripheral cells existing at
      low oxygen tension may be limited by the metabolism of tirapazamine by more
      proximal cells existing at moderate oxygen tension. Simulations found that
      tirapazamine reached only 10% of the blood concentration at cells most peripheral
      to blood vessels. These results indicate that tirapazamine would be significantly
      cytotoxic only to cells located within approximately 75 microm of blood vessels.
      Further MCC-based modelling of extravascular drug penetration would serve as a
      means of identifying new antitumour agents with location-specific activity.

PMID- 9923553
TI  - Effects of amifostine on perfused isolated rat heart and on acute doxorubicin
      induced cardiotoxicity.
AB  - PURPOSE: To determine the effects of amifostine on an isolated perfused rat-heart
      model and its protective activity with regard to cardiotoxic doxorubicin
      perfusion. METHODS: Langendorff constant-pressure isolated rat-heart preparations
      were used to analyze the effects of the drugs during a 40-min period of perfusion
      after a 20-min stabilization interval. The first study was conducted with
      amifostine alone (controls and 10(-6), 10(-5), and 10(-4) M amifostine; n=6 in
      each group). The second study was conducted with amifostine and doxorubicin
      (controls, 2.5 x 10(-5) M doxorubicin, 2.5 x 10(-5) M doxorubicin and 10(-5) M
      amifostine, and 2.5 x 10(-5) M doxorubicin and 10(-4) M amifostine; n=4 in each
      group). RESULTS: Amifostine had no significant effect on hemodynamic parameters
      at 10(-6), 10(-5), and 10(-4) M concentrations. However. amifostine increased the
      coronary flow expressed as a percentage+/-SEM of the baseline flow as follows:
      82+/-4% for controls, 95+/-6% for 10(-6) M amifostine, (P=0.13), 111+/-4% for 10(
      5) M amifostine (P < 0.01), and 104+/-3% for 10(-6) M amifostine (P < 0.01). When
      we commenced an amifostine perfusion 20 min in advance of and then during a 40
      min perfusion with doxorubicin, at a cardiotoxic concentration of 2.5 x 10(-5) M
      the left ventricular pressures (LVDP, expressed as percentages +/-SEM of the
      baseline LVDP before doxorubicin) were 55+/-3% for the doxorubicin controls, 68+/
      2% for doxorubicin with 10(-5) M amifostine (P=0.05), and 80+/-3% for doxorubicin
      with 10(-4) M amifostine (P < 0.01). Whether this protective effect might be
      related to the known free-radical-scavenging activity of amifostine remains to be
      determined. CONCLUSION: On a Langendorff-type model of rat heart, 10(-5) and 10(
      4) M amifostine alone induced a coronary dilation and, when associated with a
      cardiotoxic concentration of 2.5 x 10(-5) M doxorubicin, 10(-5) and 10(-4) M
      amifostine displayed a cardioprotective effect.

PMID- 9923552
TI  - Bioavailability and phase II study of oral UFT plus leucovorin in patients with
      relapsed or refractory colorectal cancer.
AB  - PURPOSE: This study was undertaken to address the influence of concurrent
      administration on the pharmacokinetics of UFT (uracil plus tegafur) and
      leucovorin (LV), and to measure the antitumor activity of a 28-consecutive-day
      oral regimen of UFT plus LV in patients with relapsed or refractory colorectal
      cancer. METHODS: Patients with advanced measurable colorectal cancer who had
      failed previous therapy with intravenous bolus 5-fluorouracil (5-FU) were
      eligible. Patients were treated with UFT 300 mg/m2 per day plus LV 90 mg per day
      in three divided doses every 8 h for 28 days, repeated at 35-day intervals. In
      addition, a three-treatment by three-period crossover bioavailability comparison
      of oral LV 30 mg plus UFT 200 mg versus either LV or UFT alone was scheduled for
      the 8 days preceding the first cycle of therapy. RESULTS: Of 19 patients
      enrolled, 18 were assessable for pharmacokinetics and response. When LV was
      coadministered with UFT, there were no statistically significant effects on
      tegafur, uracil, or 5-FU Cmax, AUC, or Tmax with the exception of a delayed Tmax
      for tegafur (P=0.03). No statistically significant differences were found in LV
      and 5-methyltetrahydrofolate plasma levels when LV was administered alone or with
      UFT. However, wide interpatient variability was observed for all parameters.
      There were no antitumor responses seen. CONCLUSIONS: Although the Tmax for
      tegafur is delayed with the concurrent administration of LV, there were no
      differences (P > 0.05) in any pharmacologic parameters that are of likely
      clinical significance. However, the great interpatient variability observed in
      UFT and LV pharmacology may have obscured true bioavailability effects in this
      small patient population. Daily oral UFT plus LV is inactive as second-line
      therapy in patients who have failed bolus 5-FU.

PMID- 9923554
TI  - Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)
      adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by
      oral administration.
AB  - 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine (Cl-F-araA) is a
      novel deoxyadenosine analog, which inhibits DNA synthesis by inhibiting DNA
      polymerase alpha and ribonucleotide reductase. Cl-F-araA shows potent
      antiproliferative activity against several leukemic cell lines including those of
      human origin and is also effective against murine solid tumors, in particular
      being curative against colon tumors. PURPOSE: We therefore decided to investigate
      whether Cl-F-araA is effective against human colon tumors, in particular by oral
      administration, since it has improved stability compared with other
      deoxyadenosine analogs. METHODS: Antiproliferative activity in vitro was
      determined from cell counts. Subcutaneously inoculated xenograft models and a
      liver micrometastases model were used for assessment of antitumor activity in
      vivo. RESULTS: Cl-F-araA showed potent antiproliferative activity against four
      human colon tumor cell lines (HCT116, HT-29, DLD-1, WiDr), with a 50% growth
      inhibitory concentration (IC50) of 0.26 microM with a 72-h exposure. This
      activity was greater than those of fludarabine desphosphate and cladribine, other
      deoxyadenosine analogs, which showed IC50 values of 19 microM and 0.35 microM,
      respectively. Cl-F-araA showed potent antitumor activity against four human colon
      tumor xenograft models (HT-29, WiDr, Co-3, COLO-320DM) in a 5-day daily
      administration schedule, which was shown to be the most effective of three
      administration regimens tested (single, twice-weekly, 5-day daily). In
      particular, oral administration showed significantly superior activity, with a
      regressive or cytostatic growth curve, compared with intravenous administration.
      In addition, Cl-F-araA was effective at only one-sixteenth of the maximum dose
      tested in a 10-day daily administration schedule. Therapeutic efficiency seemed
      to increase in proportion to the frequency of administration. Cl-F-araA also
      decreased liver micrometastases created by intrasplenic injection of human colon
      tumor cells, leading to complete suppression at the maximum dose tested.
      CONCLUSIONS: These results suggest that Cl-F-araA might be clinically effective
      against human colon cancers using a daily oral administration schedule.

PMID- 9923555
TI  - The antitumor efficacy of cytotoxic drugs is potentiated by treatment with PNU
      145156E, a growth-factor-complexing molecule.
AB  - PNU 145156E (formerly FCE 26644) is a noncytotoxic molecule whose antitumor
      activity is exerted through the formation of a reversible complex with
      growth/angiogenic factors, thus inhibiting their induction of angiogenesis. We
      studied in vitro and in vivo the activity of PNU145156E in combination with the
      four cytotoxic drugs doxorubicin, cyclophosphamide, methoxymorpholinyldoxorubicin
      (MMDX, FCE 23762, PNU152243), and 9-aminocamptothecin against M5076 murine
      reticulosarcoma. In vitro, PNU 145156E did not modify the cytotoxicity of the
      four drugs or the cell-cycle block induced by doxorubicin. In vivo, at the
      optimal dose of each compound, the antitumor activity was significantly increased
      in all combinations, with no associated increase in general toxicity being
      observed. In healthy mice treated with cyclophosphamide or doxorubicin the
      association with PNU 145156E did not enhance the myelotoxic effect induced by the
      two cytotoxics. These results indicate that two drugs affecting solid tumor
      growth through two different mechanisms-growth factor blockage and cell
      proliferation can be combined, resulting in increased antitumor efficacy with no
      additive toxicity.

PMID- 9923556
TI  - Intrathecal 5-fluoro-2'-deoxyuridine (FdUrd) for the treatment of solid tumor
      neoplastic meningitis: an in vivo study.
AB  - To evaluate the possible intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for
      neoplastic meningitis, its antitumor activity and neurotoxicity in vivo were
      assessed. FdUrd at doses in the range 5-100 microg/animal was effective against
      meningeal carcinomatosis using Walker 256 carcinoma cells in rats and MM46
      mammary cancer cells in mice and against meningeal gliomatosis using 203 glioma
      cells in mice. After four intrathecal injections, FdUrd at these doses also
      showed minimal neurotoxicity in the C57BL/6 mouse brain. To estimate the
      mechanism of FdUrd efficacy, thymidine phosphorylase (TPase) and thymidine kinase
      (TK), key enzymes in the metabolism of FdUrd, were measured in rat, mouse and
      normal human brain tissue, and in human brain tumor tissues and cerebrospinal
      fluid (CSF) from patients with malignant brain tumors including meningeal
      carcinomatosis. TPase levels were lower in brain and malignant brain tumors than
      in other organs and their tumors. Moreover, the activity of TPase in the gray
      matter of human brain, which faces the cerebrospinal fluid across the cortical
      surface and into which malignant cells invade in meningeal carcinomatosis, was
      lower than that in the white matter. TK was undetectable, and TPase was detected
      (at very low concentrations) in only 4 of 56 patients with brain tumors or
      meningeal carcinomatosis. These findings indicate that brain tissue and CSF are
      favorable sites for FdUrd chemotherapy because the rate of conversion of FdUrd to
      5-FU would be minimal. In conclusion, FdUrd is potentially useful for intrathecal
      treatment of neoplastic meningitis from primary brain tumors and systemic cancer.

PMID- 9923557
TI  - Docetaxel and granulocyte colony-stimulating factor in patients with advanced non
      small-cell lung cancer previously treated with platinum-based chemotherapy: a
      multicenter phase II trial.
AB  - PURPOSE: To investigate the activity of docetaxel and granulocyte colony
      stimulating factor support (G-CSF) in patients with advanced non-small-cell lung
      cancer (NSCLC) previously treated with cisplatin. PATIENTS AND METHODS: A total
      of 60 patients with locoregional and metastatic NSCLC who had relapsed or
      progressed after first-line treatment with cisplatin-based regimens were enrolled
      into the trial. Docetaxel at 100 mg/m2 was given as a 1-h infusion with G-CSF
      (rhG-CSF given s.c. at 150 microg/m2) support from day 2 to day 8 every 3 weeks;
      all patients received premedication with corticosteroids. RESULTS: In all, 1
      (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial
      response (PR), respectively, for an overall response rate of 25% (95% CI 14.0
      35.9%); stable disease (SD) and progressive disease (PD) were documented in 18
      (30%) and 27 (45%) patients, respectively. The median duration of response was 20
      weeks and the median time to tumor progression was 28 weeks. The median overall
      survival was 32 weeks and the 1-year survival rate was 23%. A total of 263
      courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia
      occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients
      requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade
      2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4
      (7%). Other toxicities were mild. CONCLUSIONS: Docetaxel has considerable single
      agent activity in patients with NSCLC who have relapsed or progressed after first
      line chemotherapy with cisplatin-based regimens.

PMID- 9923558
TI  - Fractionated administration of high-dose cyclophosphamide: influence on dose
      dependent changes in pharmacokinetics and metabolism.
AB  - PURPOSE: The alkylating agent cyclophosphamide (CP) is a prodrug that is
      metabolized to both cytotoxic and inactive compounds. We have previously shown
      that following dose escalation from conventional-dose (CD) to high-dose (HD)
      levels; the fraction of the dose cleared by bioactivation is significantly
      decreased (66% versus 48.5%) in favor of inactivating elimination pathways when
      the HD is given as a single 1-h infusion. Based on the concept of bioactivating
      enzyme saturation with increasing doses, we investigated the influence of
      fractionated application of HD-CP on dose-dependent changes in metabolism.
      PATIENTS AND METHODS: Plasma concentrations of CP (measured by high-performance
      liquid chromatography, HPLC) and urinary concentrations of CP and its major
      metabolites (quantified by [31P]-nuclear magnetic resonance spectroscopy; [31P]
      NMR spectroscopy), were determined in four patients with high-risk primary breast
      cancer who received adjuvant chemotherapy including both CD-CP (500 mg/ m2
      infused over 1 h) and split HD-CP (50 mg/kg infused over 1 h on each of 2
      consecutive days (d): d1 and d2. RESULTS: (Data are given as mean values for CD
      and d1/d2 of HD, respectively). Systemic clearance (CL) of CP was similar during
      CD and d1 of HD, but significantly increased on d2 of HD (CL: 83 and 78/115
      ml/min; P < 0.01 for d1 versus d2). The latter was translated into an increase in
      formation CL of both active (+ 16.4 ml/min) and inactive metabolites (+ 17.6 ml/
      min) and reflects autoinduction of metabolism. As compared with CD-CP, no
      statistically significant decrease was observed in the relative contribution of
      bioactivation CL to overall CL during both days of HD (63% versus 57%/53%).
      Recovery of intact CP in 24-h urine corresponded to 24%, 29%, 22% of the dose (P
      < 0.05 for d1 versus d2 of HD). CONCLUSIONS: Following dose escalation of CP,
      dividing the high dose over 2 days instead of one single infusion may favorably
      impact the metabolism of CP in terms of bioactivation. In addition, on day 2 of a
      split regimen, renal elimination of CP is decreased, which implies that more drug
      is available for metabolism.

PMID- 9923560
TI  - Hydrogen peroxide-induced vascular relaxation in porcine coronary arteries is
      mediated by Ca2+-activated K+ channels.
AB  - Hydrogen peroxide (H2O2) elicited concentration-dependent relaxation of
      endothelium-denuded rings of porcine coronary arteries. The relaxation induced by
      the H2O2 was markedly attenuated by 10 microM 1H-[1,2,4]oxadiazolo
      [4,3,a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase, or by
      100 nM charybdotoxin, an inhibitor of large-conductance Ca2+-activated K+ (KCa)
      channels. A combination of the ODQ and charybdotoxin abolished the H2O2-induced
      relaxation. Pretreatment with 25 microM of an Rp stereoisomer of adenosine-3',5'
      cyclic monophosphothioate (Rp-cAMPS), 20 microM glibenclamide, or 1 mM 4
      aminopyridine did not affect the vascular response to H2O2. The presence of
      catalase at 1000 U/ml significantly attenuated the H2O2-induced relaxation.
      Exposure of cultured smooth muscle cells to H2O2 activated KCa channels in a
      concentration-dependent manner in cell-attached patches. Pretreatment with
      catalase significantly inhibited the activation of KCa channels. Rp-cAMPS did not
      inhibit the H2O2-induced activation of KCa channels. The activation of KCa
      channels by H2O2 was markedly decreased in the presence of ODQ. However, even in
      the presence of ODQ, H2O2 activated KCa channels in a concentration-dependent
      manner. In inside-out patches, H2O2 significantly activated KCa channels through
      a process independent of cyclic guanosine 3',5'-monophosphate (cGMP). In
      conclusion, H2O2 elicits vascular relaxation due to activation of KCa channels,
      which is mediated partly by a direct action on the channel and partly by
      activation of soluble guanylate cyclase, resulting in the generation of cGMP.

PMID- 9923559
TI  - Reciprocal change in angiotensinogen mRNA expression in rat myocardium and liver
      after myocardial infarction.
AB  - The aim of this study was to analyze sequential change of angiotensinogen (Ao)
      mRNA expression in rat liver and noninfarcted myocardium after myocardial
      infarction (MI). Female sprague-Dawley rats were subjected either to left
      coronary artery occlusion or sham operation. Three weeks after MI, coronary
      artery ligation resulted in comparable infarct sizes. A hypokinetic thin anterior
      wall and remarkable dilatation of the left ventricle, as well as decreased
      contractility (left ventricular end-systolic dimension = 6.0+/-0.4, 3.3+/-0.2, LV
      end-diastolic dimension = 7.9+/-0.3, 5.9+/-0.2 mm, and fractional shortening =
      25.3+/-3.1%, 45.1+/-3.3%) were shown in the MI and sham group, respectively, by
      echocardiography (P < 0.01). Experimental MI caused a significant fall in
      systolic blood pressure (MI 90+/-5.0, vs sham 130+/-7.5 mmHg; P< 0.01) and
      significantly higher left ventricular end-diastolic pressure (MI 21+/-1.5, vs
      sham 11+/-1.0 mmHg: P < 0.01). At 4, 18, and 24h after MI, liver Ao mRNA levels,
      as shown by Northern blot analysis, had increased by up to four times
      (Ao/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) = 1.4+/-0.1 and 6.0+/-0.2 at
      baseline and 4h after MI, respectively (P < 0.01). After sham surgery, however,
      the corresponding increase was slight (maximal 1.5-fold). Three days after MI,
      liver mRNA had returned to the baseline level. In contrast, ATG mRNA expression
      in noninfarcted myocardium, as shown by reverse transcription-polymerase chain
      reaction and Southern blotting, decreased transiently during the acute phase. It
      returned to its baseline level within 3 days, and then increased further (Ao/
      GAPDH = 2.9+/-0.6, 0.3+/-0.1, 3.2+/-0.8, and 3.7+/-0.8 at baseline, 24h, 3 days,
      and 3 weeks after MI, respectively). In conclusion, it can be stated that after
      MI, the Ao gene contributes, acutely in the liver and chronically in the
      myocardium, to the maintenance of hemodynamic homeostasis during the acute phase
      and ventricular remodeling during the chronic phase.

PMID- 9923561
TI  - Halofuginone inhibits neointimal formation of cultured rat aorta in a
      concentration-dependent fashion in vitro.
AB  - Halofuginone, an anticoccidial quinoazolinone, can specifically inhibit collagen
      type alpha1 (I) synthesis and gene expression, and also inhibits cultured smooth
      muscle cell proliferation. The aim of this study was to investigate the effect of
      halofuginone on neointimal formation of rat aorta after culture in a
      concentration-dependent manner in vitro. Thoracic aorta of Wistar rats was
      removed and manipulated to damage the endothelium under sterile conditions, and
      culture for 15 days in halofuginone-free or halofuginone-added culture medium (n
      = 20). Segments of cultured aorta were studied by histologic and
      immunohistochemical methods. Proliferation of neointimal layers consisting of
      loose multilayer cellular structure was observed in the halofuginone-free control
      group after 15 days of rat aorta culture, and neointimal formation was
      significantly decreased as an increasing concentration of halofuginone was added.
      As with precultured fresh aorta, no intimal proliferation was observed in the
      cultured segments of aorta with 500 ng/ml halofuginone added to culture medium.
      The proliferation of cell nuclear antigen index was significantly higher in the
      halofuginone-free control group than that in the halofuginone-added groups. The
      present results suggest that halofuginone can inhibit neointimal formation of rat
      aorta after culture in a concentration-dependent fashion in vitro.

PMID- 9923562
TI  - Association between the degree of platelet-derived growth factor-A chain mRNA
      expression and coronary arteriosclerosis in the transplanted heart.
AB  - Although intimal and medial proliferation of smooth muscle cells is recognized as
      one of the key mechanisms in the development of graft coronary arteriosclerosis,
      the role of platelet-derived growth factor (PDGF) in this process is still
      uncertain, because of the undetermined pathogenesis of graft coronary
      arteriosclerosis (GCA). In the present study, the correlation between the extent
      of GCA and the degree of PDGF-A chain expression in cardiac grafts was
      investigated in 21 rats with GCA of varying extent. Lewis rats underwent
      heterotopic heart transplantation from Wistar King donors and were treated with
      cyclosporine A (10 mg/kg/day) (n = 7), 15-deoxyspergualin (5 mg/kg/day) (n = 7),
      or Multiglycosidorum tripterygii (MT) (30 mg/kg/day) (n = 7). Histological
      evaluations of coronary arteriosclerosis, as well as Northern blot analysis of
      graft PDGF-A chain expression were made, 60 days after transplantation. Graft
      coronary arteriosclerosis of varying extent was observed among the 21
      transplanted hearts. Significant correlations were found between the PDGF-A chain
      mRNA expression of cardiac allograft and the grade of arterial intimal thickening
      (Spearman's r = 0.76, P < 0.005) as well as the incidence of diseased vessels (r
      = 0.82, P < 0.001). The PDGF-A chain mRNA expression of the cardiac allograft is
      associated with the extent of GCA, indicating that PDGF-A plays an important role
      in the development of GCA.

PMID- 9923563
TI  - Heat shock protein expression in hearts hypertrophied by genetic and nongenetic
      hypertension.
AB  - Genetically hypertensive animals are characterized by greater thermosensitivity
      and overexpression of heat shock proteins (HSP) upon thermal stimulation. We
      examined HSP72 expression under conditions of brief coronary occlusion or thermal
      stimulation, and the effects of the severity of these stimuli and of myocardial
      hypertrophy on the expression in hearts of spontaneously hypertensive rat (SHR)
      and Wistar Kyoto rat (WKY) groups, A snare was created around the left coronary
      artery in the SHR (n = 16) and WKY (n = 19) groups. In 7 WKY rats, the ascending
      aorta was banded and a snare was created simultaneously (WKY-AoB). By tying the
      snare, 4 weeks later, we applied 5- or 10-min coronary occlusion without opening
      the chest. For thermal stimulation, the SHR (n = 13) and WKY (n = 11) rats were
      placed in a 42 degrees C chamber for 15 or 40 min. The mRNA or protein level was
      estimated 1 or 24h after stimulation. In the SHR vs WKY groups, the mRNA and
      protein levels were higher after 5-min occlusion or 15-min thermal stimulation.
      After 10-min occlusion or 40-min thermal stimulation the difference was no longer
      observed. The overexpression was not observed in the WKY-AoB group despite the
      presence of hypertrophy similar to that seen in the SHR group (3.11+/-0.11 vs
      3.20+/-0.06 mg/g in left ventricular weight/body weight). The HSP72 was
      overexpressed in hearts of genetically hypertensive animals after brief ischemia.
      Differential expression between the two groups was observed after mild stimuli,
      but not after more severe stimuli. Cardiac hypertrophy was not a major factor for
      determining the overexpression of HSP72.

PMID- 9923564
TI  - Change in heart rate variability preceding ST elevation in a patient with
      vasospastic angina pectoris.
AB  - A case of vasospastic angina (VSA) in a 62-year-old man with frequent ST
      elevation throughout the day was reported. His coronary angiogram showed that
      intracoronary methylergometrine had induced total occlusion due to a vasospasm.
      Analysis by Holter monitoring suggested that the autonomic nervous system would
      contribute differently to the initiation of the coronary spasm depending on
      whether the VSA attacks occurred during the daytime or at night. During the
      nighttime, the high-frequency power (HF: 0.15-0.4 Hz) decreased during the 2 min
      before ST elevation, and the heart rate increased immediately before ST
      elevation. The low-frequency power (LF: 0.04-0.15 Hz) and the ratio of LF to HF
      (LF/HF) did not significantly change before ST elevation. In contrast, each of
      the heart rate variability components and the heart rate did not significantly
      change before ST elevation during the daytime. Thus, the pathophysiology of VSA
      during the daytime and nighttime seems to be different in its relation to
      autonomic tone. During the nighttime, vagal withdrawal may be a component of the
      mechanisms leading to VSA, while during the daytime, a change in autonomic tone
      may not play a major role in this case.

PMID- 9923565
TI  - Echocardiography of a right atrial mass in hepatocellular carcinoma.
AB  - Antemortem diagnosis of hepatocellular carcinoma with a tumor thrombus extending
      into the right atrium has been rarely observed. Although echocardiography allows
      easy detection of the intracardiac mass, reports of echocardiographic
      descriptions of a right atrial mass associated with hepatocellular carcinoma are
      few. Herein, we describe two cases of hepatocellular carcinoma with a tumor
      thrombus in the right atrium detected by transthoracic echocardiography. In one
      of the patients we also performed transesophageal echocardiography. Neither
      patient had cardiac symptoms or signs. Thus, echocardiographic examination is
      very important in patients with hepatocellular carcinoma, with or without cardiac
      symptoms and signs.

PMID- 9923566
TI  - Assessment of deep vein thrombosis prophylaxis in surgical patients: a study
      conducted at Nancy University Hospital, France.
AB  - OBJECTIVE: This retrospective evaluation aimed to assess the adequacy of
      prophylaxis against thromboembolism prescribed to surgical patients at the
      authors' institution, and to compare it with generally accepted published
      guidelines. Aspects considered were indications for prophylaxis, regimens used
      and monitoring. METHODS: Eleven units (nine surgical and two surgical intensive
      care) took part in the survey on a voluntary basis. The clinical audit system
      used involved developing a set of criteria based on existing guidelines,
      comparing observed practice with those recommendations, analysing the factors
      underlying any deviation and developing corrective measures. RESULTS: When the
      medical records of 117 patients hospitalized in October 1995 were examined,
      prophylaxis against deep vein thrombosis was documented in 86 (low molecular
      weight heparin in 85, dextran in one). No associated physical preventative
      measures were recorded. Indications and dosage were appropriately handled in
      90.7% and 75.2% of patients, respectively. Ninety-five cases were outside the
      reference criteria: 74 for excluded surgical indications, 13 which involved
      laparoscopy, and eight in which spinal or epidural anaesthesia was administered.
      Platelet count was performed in 73.8% of cases before prophylactic treatment, and
      in 23.10% during its course. Anti-Xa activity was measured in 0.4% of cases.
      Analysis of causes showed that guidelines were not complied with either because
      of lack of organization, or because of disagreement with them. DISCUSSION: In
      this study, indications for prophylaxis were well established and heparin dosages
      used were not fundamentally flawed. The weak point in practice was a failure to
      carry out platelet counts, particularly during the course of treatment.
      Appropriate corrective action consists of disseminating guidelines and relevant
      information, and using a preoperative checklist to assess thromboembolic risk.
      CONCLUSION: Physicians agree that opportunities to improve preventative practices
      exist, and that the quality improvement programme should be pursued.

PMID- 9923567
TI  - Relation between unbound plasma concentrations and toxicity in a prolonged oral
      etoposide schedule.
AB  - OBJECTIVE: This study was undertaken in order to evaluate the impact of
      pharmacokinetics on the toxicity of oral etoposide administered daily for 21
      days. METHODS: The daily dose was 50 mg/m2. Thirty-two patients 24 males and
      eight females, 36 76 years old, treated for various tumour types), were
      evaluated. Blood samples were obtained on day 1 for all patients, and on day 21
      for 16 patients. Plasma etoposide concentrations were determined by high
      performance liquid chromatography, and etoposide plasma protein binding by
      equilibrium dialysis. RESULTS: On day 1, the mean value (with coefficient of
      variation for interindividual variability) for the unbound fraction (fu), area
      under the concentration versus time curve (AUC), and unbound AUC was 9.8% (59%),
      34 mg x h/l (39%), and 3.5 mg x h/l (92%), respectively. The ratio between AUC on
      day 1 and day 21 ranged between 0.5 and 1.8 (mean 0.9, with CV 33%). The plasma
      trough unbound concentrations and the unbound AUCs both corresponding to the
      first administration were significantly higher in the 11 patients who had a
      severe neutropenia than in the 21 patients who had no or moderate toxicity.
      However, total etoposide concentrations did not differ between these two groups.
      A limited sampling strategy using the NONMEM program and a database of 89
      patients previously studied was performed. The optimal sampling schedule (i.e. 1,
      4, and 24 h after oral etoposide administration) allowed to obtain the AUC
      accurately on day 1. CONCLUSION: Individual adjustment of oral etoposide based on
      unbound pharmacokinetics after the first administration appears relevant and
      feasible.

PMID- 9923568
TI  - Education in clinical pharmacology at the Rijeka School of Medicine, Croatia.
AB  - OBJECTIVE: Irrational drug prescribing is a global problem that exists both in
      developed and developing countries. Education is the key to improved
      effectiveness and safety in drug therapy. Development of clinical pharmacology
      (CP) as an independent discipline at the Rijeka School of Medicine has been slow
      and unsatisfactory. It was taken only as a part of some postgraduate courses. In
      the 1995/1996 academic year clinical pharmacology was offered for the first time
      to sixth year medical students as a non-mandatory subject. The purpose of this
      study was to emphasize the importance of education in clinical pharmacology at
      the Rijeka School of Medicine. METHODS: This survey was an uncontrolled study
      based on responses to questionnaires and a test consisting of written patient
      problems given to sixth year medical students and to general practitioners who
      were following a course in clinical pharmacology. RESULTS: The results of the
      questionnaire showed that both undergraduate and postgraduate students consider
      that they are not being adequately trained to prescribe drugs rationally and that
      they believe that clinical pharmacology should become a mandatory subject in the
      undergraduate medical curriculum. The results of the written patient problem test
      support this. Both groups of students demonstrated greater skills in solving the
      diagnostic part than the therapeutic part of the test. A great improvement in the
      students' ability to solve the therapeutic part was observed after they had
      completed the CP course. CONCLUSION: The results of this survey underline the
      necessity of education in clinical pharmacology.

PMID- 9923569
TI  - Cardiovascular effects of mibefradil in hypertensive patients with obstructive
      sleep apnea.
AB  - OBJECTIVE: Hypertension is often seen in obstructive sleep apnea (OSA) and is
      characterized by increased sympathetic activity, depressed baroreflex and
      accentuated vascular responsiveness. The objective of this study was to
      investigate the effects of the new T-selective calcium channel blocker mibefradil
      on invasively measured blood pressure (BP) and heart rate in hypertensive
      patients with OSA. METHODS: The present study was a double-blind, randomized and
      placebo-controlled before and after trial in two parallel groups. Fifty-three men
      aged 23 69 years with systemic hypertension and OSA were recruited from the
      Outpatient Department of the Marburg University Sleep Laboratory and hospitalized
      for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8
      days. The main outcome measure was the mean arterial (radial) BP monitored
      continuously during nocturnal sleep and during standardized daytime physical and
      psychological performance testing. RESULTS: Mibefradil lowered mean arterial BP
      and heart rate with (SD) during the entire measurement period compared with
      placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34
      (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal
      sleep and performance testing, including graded exercise. Adverse events did not
      differ compared with placebo. CONCLUSION: Mibefradil is an effective but well
      tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in
      conditions known to increase BP.

PMID- 9923570
TI  - Ciprofibrate treatment in patients with atherogenic lipoprotein phenotype:
      effects on HDL quality, LDL susceptibility to oxidation and DNA damage.
AB  - OBJECTIVES: This study was conducted to examine a complex effect of ciprofibrate
      therapy in patients with atherogenic lipoprotein phenotype. METHODS: Effects of
      ciprofibrate were studied on HDL subpopulations, HDL ability to esterify
      cholesterol (FER(HDL)), susceptibility of LDL to oxidation as well as on in vivo
      oxidative DNA damage in peripheral lymphocytes, measured as strand breaks (SBs)
      by the comet assay. RESULTS: Ciprofibrate treatment significantly decreased total
      cholesterol, and triglycerides, and increased HDL-cholesterol. The FER(HDL)
      showed a significant reduction (29.5+/-7.4 to 23+/-7.5% x h(-1), P=0.0001). The
      relative concentrations of HDL subclasses did not differ between baseline and
      after treatment. Ciprofibrate induced a significant increase in LDL oxidation lag
      time (93+/-7 to 102=11 min, P=0.02) and a decrease in DNA strand breaks (34.0+/
      16.2 to 17.8+/-7.5, P=0.02). A significant correlation between maximal rate of
      diene production and strand breaks was found (r=0.55, P=0.01). These findings may
      be explained by an improvement of LDL resistance to oxidation, resulting in a
      decrease in oxidatively modified LDL's cytotoxic effect. CONCLUSION: Ciprofibrate
      treatment favourably affected the quality of plasma HDL, probably by the
      improvement of triglyceride rich lipoprotein metabolism and/or LDL subpopulation
      profile, increased LDL resistance to oxidation, and decreased the level of DNA
      damage in peripheral lymphocytes.

PMID- 9923572
TI  - Effects of very low dose and enteric-coated acetylsalicylic acid on prostacyclin
      and thromboxane formation and on bleeding time in healthy subjects.
AB  - OBJECTIVE: Low dose acetylsalicylic acid (ASA) is widely used as an anti
      aggregatory agent in the primary and secondary prevention of cardiovascular
      diseases. In an effort to spare prostacyclin formation and to reduce
      gastrointestinal side-effects, both very low doses and enteric-coated
      formulations of ASA have been introduced. However, it still remains unclear
      whether these different formulations and dosages are equally effective with
      respect to inhibition of platelet aggregation and thromboxane A2 (TXA2)
      formation. METHODS: In a randomized study, we therefore investigated the effects
      of 100 mg ASA plain (p), 100 mg ASA enteric-coated (ec) and 40 mg ASA (p) to 36
      healthy male subjects given for 7 days on platelet aggregation and endogenous
      prostanoid formation rates. Platelet aggregation and platelet TXB2 release in
      platelet rich plasma (PRP) and serum TXB2 and 6-keto-PGF1alpha levels were
      determined at baseline and after 7 days of each medication. The urinary
      metabolites of TXA2 (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6-keto
      PGF1alpha) were measured by gas chromatography/tandem mass spectrometry in 24-h
      urines at baseline and on day 7 of each medication. RESULTS: Collagen-induced
      platelet aggregation was 73.1+/-1.6% of maximal aggregation at baseline. It was
      inhibited by 68.9%, 58.6% and 24.0% by ASA 100 mg plain, 100 mg enteric-coated,
      and 40 mg plain on day 7, respectively. Platelet TXB2 release was 11592.0+/-367.5
      pg x ml(-1) PRP. It was inhibited by 90.1%, 86.5%, and 55.2% by ASA 100 mg plain,
      100 mg enteric-coated, and 40 mg plain, respectively. Serum TXB2 was almost
      completely reduced on day 7 by 100 mg ASA, but not by 40 mg ASA; serum 6-keto
      PGF1alpha was slightly, but significantly reduced in all three groups. Urinary
      2,3-dinor-TXB, excretion was 196.0+/-41.5 pg x mg(-1) creatinine at baseline. It
      was reduced by 80.3% and 79.1% by ASA 100 mg plain and enteric-coated,
      respectively (each P < 0.05 versus baseline), but only by 55.4% by ASA 40 mg
      plain (P < 0.05 versus both formulations of ASA 100 mg). CONCLUSIONS: Our present
      data show that the plain and enteric-coated formulations of 100 mg ASA are
      equally effective in inhibiting platelet aggregation, platelet thromboxane
      production, and urinary 2,3-dinor-TXB2 excretion rates. In contrast, a very low
      dose of 40 mg ASA was significantly less effective in inhibiting these indices of
      platelet activation in healthy human subjects. ASA enteric-coated 100 mg may be a
      useful alternative to 100 mg ASA (p) in patients with gastrointestinal side
      effects, whereas 40 mg ASA (p) may be too low to inhibit sufficiently platelet
      activity in patients with cardiovascular diseases in whom platelet activity is
      increased.

PMID- 9923571
TI  - Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs.
AB  - OBJECTIVE: To analyse drug-specific clinical characteristics and to investigate
      the possible influence of epidemiological and other factors on thrombocytopenia
      induced by selected non-cytotoxic drugs. METHODS: A retrospective analysis of
      drug-induced thrombocytopenia reported to the Danish Committee on Adverse Drug
      Reactions. One-hundred and ninety-two cases induced by the most frequently
      reported drugs were included and analysed from data extracted from report forms
      and discharge summaries. RESULTS: Pronounced drug-specific differences in the
      clinical appearance of thrombocytopenia were registered. Severe thrombocytopenia
      with haemorrhagic manifestations was reported following exposure to gold salts,
      non-steroid anti-inflammatory drugs, sulfonamide antibiotics, cinchona alkaloids
      and vaccines. Valproic acid-induced thrombocytopenia was dose-dependent. The
      differences were primarily determined by the drug itself and also by its usage
      pattern. No specific patient-related factor responsible for the heterogeneity of
      the clinical appearance of the adverse reaction was identified. Factors related
      to the physician, such as monitoring recommendations or level of attention
      towards the adverse reaction, seemed to be of little significance. CONCLUSION:
      The primary determinant of the clinical characteristics of thrombocytopenia
      induced by noncytotoxic drugs is the offending drug.

PMID- 9923573
TI  - Pharmacokinetics of a novel 5-lipoxygenase inhibitor (ABT-761) in pediatric
      patients with asthma.
AB  - OBJECTIVE: The pharmacokinetics of an N-hydroxyurea analog, ABT-761 in asthmatic
      pediatric patients with asthma were investigated. METHODS: A total of 24 patients
      were enrolled into this 8-day single- and multiple-dose study. Patients received
      daily doses of ABT-761 according to their body weight: patients of 20-38 kg
      received 50 mg; patients >38 kg but < or = 55 kg received 100 mg, and patients
      >55 kg received 150 mg. RESULTS: The mean values for the terminal phase t1/2 were
      16-17 h after multiple-dose administration. When normalized for body weight, the
      mean day 8 Cl(f) values for 50-, 100-mg, and 150-mg doses were 0.57 (n=13), 0.51
      (n=10), and 0.43 (n=1) ml x min(-1) x kg(-1), respectively, while the mean Vz/f
      values ranged from 0.75 to 0.77 l x kg(-1). The mean accumulation ratio observed
      (day 8 to day 1 AUC0-24 ratio) of ABT-761 was approximately 1.7, which is
      consistent with the t1/2 of this drug. Body weight, age, and body surface area
      were virtually identical in explaining the variability in dose-normalized Cmax
      and AUC values (R2=0.61-0.68). The percents of variance explained by these three
      variables were within a range of 3% for each pharmacokinetic parameter.
      CONCLUSIONS: The pharmacokinetics of ABT-761 in children were similar to those
      previously reported in adults. Body weight, age, or body surface area can be used
      to provide dosing adjustment for ABT-761 in pediatric patients.

PMID- 9923574
TI  - Assessment of the value of therapeutic monitoring of tacrine in Alzheimer's
      disease.
AB  - OBJECTIVES: The purpose of this study was to validate the lower end of the
      putative therapeutic range of serum tacrine concentrations of 7-20 ng ml(-1) in
      the treatment of Alzheimer's disease. METHODS: The relationship between dose,
      steady-state serum tacrine concentrations and change in MMSE score (a measure of
      cognitive function) was examined in 106 Alzheimer's disease patients who had been
      treated with the drug for 12 weeks. RESULTS: In all, 72% of patients showed some
      response, but there was no relationship between dose and the chance of a
      favourable outcome. The proportion of patients with serum concentrations above 7
      ng x ml(-1) who improved (79%) was significantly greater than that of those with
      serum concentrations below this level (47%) (P < 0.02). Also, a significantly
      greater proportion of patients with serum concentrations above both 5 ng x ml(-1)
      and 9 ng x ml(-1) showed improvement in comparison to those with concentrations
      below these levels. CONCLUSIONS: This study indicates that therapeutic monitoring
      of serum tacrine concentrations might increase the possibility of responding to
      tacrine by some 68%. This represents an important contribution to the management
      of Alzheimer's disease patients with this drug, and may also be relevant to the
      use of the newer generation of cholinesterase inhibitors.

PMID- 9923575
TI  - Estimation of the area under the concentration-versus-time curve of carboplatin
      following irinotecan using a limited sampling model.
AB  - OBJECTIVES: The aim of this study was to develop limited sampling models for
      estimating the area under the concentration-versus-time curve (AUC) of
      carboplatin. METHODS: Based on pharmacokinetic analyses of 14 patients who
      received 300 mg x m2 of carboplatin over a 90-min infusion following irinotecan,
      we developed limited sampling models with stepwise multiple linear regression
      analysis. We validated these models to be unbiased and precise using
      pharmacokinetic data of a second group of 14 patients. We also compared the
      observed and the predicted AUC in the patients using Calvert's formula with the
      patients' renal function. RESULTS: We developed the following models: AUC (mg x
      ml(-1) x min) = 0.784 x C4 + 1.30 (r2=0.930) and AUC=0.100 x C0.25 + 0.597 x C4 +
      0.140 (r=0.992), where C0.25 and C4 denote unbound plasma concentrations (microg
      x ml(-1)) of carboplatin at 0.25 h and 4 h after the end of infusion,
      respectively. These models were validated to be unbiased and precise: a mean
      prediction error (MPE) with standard deviation (SD) = 2.41 (9.45)% and a root
      mean squared error (RMSE) = 9.42% for the one-sample model, and MPE with (SD) =
      1.22 (5.56)% and RMSE = 5.49% for the two-sample model. We also calculated
      predicted AUC in the patients using Calvert's formula: MPE with (SD)= -5.87
      (21.5)% and RMSE = 21.5%. CONCLUSIONS: These estimations were, as expected, more
      accurate than the prediction using Calvert's formula based on patients' renal
      function. The result of this study confirmed the idea that the pharmacokinetic
      parameters derived from limited sampling models would be more suitable for
      pharmacokinetic analysis of carboplatin than those obtained using Calvert's
      formula.

PMID- 9923576
TI  - Can oral contraceptive steroids influence the elimination of nifedipine and its
      primary pryidine metabolite in humans?
AB  - OBJECTIVE: To investigate the influence of oral contraceptives on cytochrome P450
      3A4 (P450NF) activity. METHODS: In 23 healthy women, the pharmacokinetics of
      nifedipine and its main metabolite dehydronifedipine in plasma were assessed
      after a single oral dose, prior to and after intake of one of two oral
      contraceptive formulations, one containing 2 mg dienogest and 0.03 mg
      ethinylestradiol (group A) and the other containing 0.125 mg levonorgestrel and
      0.03 mg ethinylestradiol (group B). RESULTS: While the intake of two oral
      contraceptives for 21 days did not influence the plasma concentration-time curve
      of unchanged nifedipine, mean AUC0-23.5 h and the mean Cmax values of
      dehydronifedipine were significantly lower in both groups tested/(24% in group A
      and 25% in group B). This observation may indicate a reduced formation rate of
      metabolites and reflects an inhibition of cytochrome P450 3A4 activity. The
      activation of the same or other metabolic degradation mechanism(s) could explain
      this result. CONCLUSION: The investigation presented demonstrates the importance
      of metabolite measurement when in vivo studies are undertaken to investigate
      different influences on drug metabolizing ability.

PMID- 9923577
TI  - Fluvoxamine inhibits the CYP2C19-catalysed metabolism of proguanil in vitro.
AB  - OBJECTIVE: The potent CYP1A2 inhibitor fluvoxamine has recently been shown also
      to be an effective inhibitor of the CYP2C19-mediated metabolism of the
      antimalarial drug proguanil in vivo. The purpose of the present study was to
      confirm this interaction in vitro. METHODS: A high-performance liquid
      chromatography (HPLC) method was developed to assay 4-chlorophenylbiguanide (4
      CPBG) and cycloguanil formed from proguanil by microsomes prepared from human
      liver. The limit of detection was 0.08 nmol mg-'. h-I. RESULTS: The formation of
      4-CPBG and cycloguanil could be described by one-enzyme kinetics, indicating that
      the formation of the two metabolites is almost exclusively catalysed by a single
      enzyme, i.e. CYP2C19 within the concentration range used, or that the
      contribution of an alternative low-affinity enzyme, probably CYP3A4, is very low.
      This notion was confirmed by the lack of potent inhibition by four CYP3A4
      inhibitors: ketoconazole, bromocriptine, midazolam and dihydroergotamine.
      Fluvoxamine was a very effective inhibitor of the oxidation of proguanil,
      displaying Ki values of 0.69 micromol x l(-1) for the inhibition of cycloguanil
      formation and 4.7 micromol x l(-1) for the inhibition of 4-CPBG formation. As
      expected, the CYP2C19 substrate omeprazole inhibited the formation of both
      metabolites with an IC50 of 10 micromol x l(-1). Norfluoxetine and sulfaphenazole
      inhibited proguanil oxidation with Ki values of 7.3-16 micromol x l(-1),
      suggesting that the two compounds are moderate inhibitors of CYP2C19.
      CONCLUSIONS: Fluvoxamine is a fairly potent inhibitor of CYP2C19 and it has the
      potential for causing drug-drug interactions with substrates for CYP2C19 such as
      imipramine, clomipramine, amitriptyline and diazepam. The combination of
      fluvoxamine and proguanil can not be recommended.

PMID- 9923578
TI  - Neither dapsone hydroxylation nor cortisol 6beta-hydroxylation detects the
      inhibition of CYP3A4 by HIV-1 protease inhibitors.
AB  - OBJECTIVE: This study examined the use of dapsone N-hydroxylation and cortisol
      6beta-hydroxylation, well accepted in vivo probes of cytochrome P4503A4 (CYP3A4)
      activity, on defining the effect of three HIV protease inhibitors on CYP3A4
      activity. METHODS: Subjects from University Hospital Infectious Disease Clinic
      about to be started on indinavir, and subjects from two clinical studies, one
      using ritonavir and the other using amprenavir, were recruited to participate in
      the study. Subjects received dapsone 100 mg p.o. followed by an 8-h urine
      collection for dapsone, dapsone N-hydroxylamine, cortisol, and 6beta
      hydroxycortisol concentrations before HIV protease inhibitor administration, and
      3 4 weeks into receiving HIV protease inhibitors. RESULTS: None of the HIV
      protease inhibitors demonstrated statistically significant alterations in dapsone
      recovery ratio and 6beta-hydroxycortisol/cortisol ratio. In fact, with ritonavir,
      the dapsone recovery ratio tended to increase rather than decrease, suggesting
      induction. These negative results were found despite evidence of CYP3A4
      inhibition by these three HIV protease inhibitors via published drug-drug
      interactions with drugs that are substrates for CYP3A4. CONCLUSIONS: These in
      vivo assays used to probe CYP3A4 activity are suboptimal, most likely because of
      the presence of extrahepatic sites of metabolism for both dapsone and cortisol,
      and multiple CYP isozymes involved in dapsone N-hydroxylation.

PMID- 9923579
TI  - Saliva-resistant coating of tablets prevents oral release of penicillin: plasma
      but not saliva equivalence.
AB  - OBJECTIVE: To investigate saliva and plasma concentrations of penicillin after
      the intake of a conventional phenoxymethylpenicillin (PcV) tablet and a tablet
      with saliva-resistant coating (PcVsr), both containing 1 g penicillin. METHODS:
      The study had an open randomized crossover design and involved 24 healthy
      subjects. Saliva and blood were sampled intermittently for 6 h after tablet
      intake. RESULTS: Within the first 10 min after tablet intake penicillin was
      detected in saliva in ten subjects taking PcV and in none taking PcVsr (P <
      0.001). These initial saliva concentrations were short-lasting, but in some
      subjects 50 to 100 times higher than those following the peak concentration in
      plasma, i.e. at 40 min or more after swallowing. From 40 min and onwards the
      saliva concentrations of penicillin were very similar for the two formulations.
      The elimination of high initial saliva concentrations may diminish ecological
      disturbances of the mouth flora as well as removing the unpleasant taste of
      penicillin. The plasma concentrations of penicillin were similar for the two
      formulations throughout the 6-h sampling period and the mean ratio of the area
      under the plasma concentration-time curve was 99% for PcVsr in relation to PcV,
      the 90% confidence interval being 86-115%. The corresponding values for the
      maximum plasma concentration were 108% and 93 127%. The time to maximum
      concentration was 45 min for PcVsr and 41 min for PcV. Thus, with regard to
      standard criteria which are based on systemic (plasma) concentrations, the
      formulations were bioequivalent despite the substantial difference in initial
      local (saliva) concentrations. CONCLUSION: Saliva-resistant coating of tablets
      can prevent oral release of penicillin without affecting the plasma
      concentrations. From a clinical point of view both local and systemic equivalence
      should be established before bioequivalence is assumed.

PMID- 9923580
TI  - Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium
      antagonist, in healthy subjects.
AB  - OBJECTIVES: The study was conducted to investigate whether oral co-administration
      with citrus juices significantly affects the pharmacokinetics and/or
      pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in
      healthy male subjects. Grapefruit juice and orange juice, which were both
      commercially available, were used in this study. METHODS: Sixteen healthy male
      Japanese subjects participated in this study and were divided into two groups for
      grapefruit juice and orange juice treatment. The study followed an open-labelled
      crossover design, comparing the effects of a single oral dose of 2 mg pranidipine
      taken together with 250 ml citrus juice or 250 ml water. Serum pharmacokinetics
      of pranidipine, adverse reactions, blood pressure, heart rate, 12-lead ECG,
      haematology, clinical chemistry and urinalysis were measured throughout the
      study. RESULTS: For grapefruit juice, mean Cmax and AUC0-24 h were significantly
      higher than those of water (P=0.0003 and 0.0005, respectively, ANOVA) with the
      ratios of log transformed values being 1.50 and 1.74, respectively. There were no
      differences in tmax and t1/2 between the juice and water treatments. A
      significant increase in heart rate (P=0.0240, ANOVA with repeated measurements)
      was observed in the juice treatment whereas there were no significant differences
      in systolic and diastolic blood pressure between the two treatments. For orange
      juice, a small decrease in mean Cmax was observed compared with water (P=0.0218,
      ANOVA) with the ratio being 0.86, but there was no significant difference in AUC0
      24h between the two treatments. No marked differences were observed in tmax and
      t1/2. Oral pranidipine administration with orange juice did not affect heart
      rate, systolic and diastolic blood pressures or other parameters for safety
      evaluation. CONCLUSIONS: Oral co-administration with grapefruit juice and
      pranidipine was associated with increased bioavailability and changed the
      pharmacodynamics of pranidipine, particularly with regard to heart rate. Orange
      juice intake with pranidipine did not markedly affect the pharmacokinetics and no
      clinically significant changes were observed in the pharmacodynamics and safety
      evaluation.

PMID- 9923581
TI  - The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of
      buspirone.
AB  - OBJECTIVE: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake
      inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of
      buspirone, a non-benzodiazepine anxiolytic agent, were investigated. METHODS: In
      a randomized, placebo-controlled, two-phase cross-over study, ten healthy
      volunteers took either 100 mg fluvoxamine or matched placebo orally once daily
      for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of
      buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were
      measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h.
      RESULTS: The total area under the plasma buspirone concentration-time curve was
      increased 2.4-fold (P < 0.05) and the peak plasma buspirone concentration 2.0
      fold (P < 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone
      was not affected. The ratio of the total area under the plasma concentration-time
      curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6)
      by fluvoxamine (P < 0.05). The results of the six pharmacodynamic tests remained
      unchanged. CONCLUSION: Fluvoxamine moderately increased plasma buspirone
      concentrations and decreased the production of the active 1-PP metabolite of
      buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4
      mediated first-pass metabolism of buspirone by fluvoxamine. However, this
      pharmacokinetic interaction was not associated with impairment of psychomotor
      performance and it is probably of limited clinical significance.

PMID- 9923582
TI  - Pharmacokinetics and safety of propiverine in patients with fatty liver disease.
AB  - OBJECTIVE: The present study was designed to assess the pharmacokinetics of
      propiverine after single and multiple dosing in patients with and without fatty
      liver disease. METHODS: The serum concentration-time curves of propiverine and
      its main metabolite propiverine-N-oxide were investigated in 12 patients with
      mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml
      x min(-1)) and in 12 controls (antipyrine clearance 42.8 ml x min(-1)). Subjects
      were treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg
      t. i. d.) to reach steady state. RESULTS: No significant differences were
      observed for propiverine and its main metabolite with regard to peak serum
      concentration (Cmax), area under the serum concentration-time curve (AUC) and
      elimination half-life (t1/2). Adverse events were reported by 12 patients. Five
      patients with fatty liver disease and seven patients with normal liver function
      complained of dry mouth and/or blurred vision. All adverse events reported were
      transient and mild. CONCLUSION: No pharmacokinetic differences relevant for
      safety were observed, comparing patients with and without fatty liver disease
      following repeated oral administration of propiverine. Thus there seems to be no
      need to adjust the dose in patients with mild to moderate impairment of liver
      function.

PMID- 9923583
TI  - The interaction of the lipase inhibitor orlistat with ethanol in healthy
      volunteers.
AB  - OBJECTIVES: The primary objective was to investigate the possible interference of
      ethanol on the orlistat effect on inhibition of dietary fat absorption and the
      possible interference of orlistat on the pharmacokinetics of ethanol. Secondary
      objectives were to assess the tolerability during concomitant dosing of orlistat
      and ethanol and to determine the ethanol effect on plasma levels of orlistat.
      METHODS: This was a double-blind, placebo-controlled, parallel, randomized study
      performed in 30 (three parallel groups of ten subjects each) healthy normal
      weight male subjects between the ages of 20 and 30 years. A 5-day run-in period
      to accustom subjects to a standardized diet of 2500 kcal/day (30% fat) and to
      establish baseline fecal fat excretion was followed by a 6-day treatment period.
      Subjects were randomly assigned to one of three treatment groups (A = orlistat
      120 mg t.i.d. and ethanol placebo, B = orlistat 120 mg t.i.d. and 40 g ethanol qd
      on days -1 and 6, and 40 g bid on days 1-5, and C = orlistat placebo tid and 40 g
      ethanol qd on days -1 and 6, and 40 g b.i.d. on days 1 5). Serial blood samples
      were collected for determination of ethanol serum concentrations at specified
      times over 5 h after each dose of ethanol on days -1 and 6, and for determination
      of orlistat plasma concentrations on days 1, 3, 5, and 6. Feces were collected
      quantitatively on days -5 through 8 for analysis of fecal fat. RESULTS: The means
      of baseline-corrected fecal fat excretion values were comparable: 23.7 g for
      group A (orlistat) and 22.7 g for group B (orlistat and ethanol). No significant
      difference was found regarding ethanol pharmacokinetic parameters between
      treatments with orlistat and placebo. No apparent differences existed between the
      number of plasma samples with measurable orlistat concentrations in groups A and
      B. CONCLUSION: Concomitant ingestion of social amounts of ethanol did not alter
      the inhibitory effect of orlistat on dietary fat absorption during short-term
      treatment (6 days) with orlistat. Short-term treatment with orlistat had no
      significant influence on ethanol pharmacokinetics.

PMID- 9923584
TI  - The arylamine N-acetyltransferase (NAT2) polymorphism and the risk of adverse
      reactions to co-trimoxazole in children.
AB  - OBJECTIVE: The evaluation of the importance of the genetically determined
      acetylation defect for the development of adverse reactions to co-trimoxazole in
      children. METHODS: The study comprised 48 children aged 3 months to 3 years, who
      were being treated for interstitial pneumonia with co-trimoxazole. During the
      treatment, daily clinical examinations and biochemical tests to monitor the
      functions in various organs enabled us to detect adverse reactions to the drug.
      The therapy was continued or discontinued according to the results of these
      examinations. In all children we identified the genotype coding for N
      acetyltransferase (NAT2). For this purpose, DNA was isolated from peripheral
      blood. Polymerase chain reaction (PCR) was then carried out, followed by
      restriction mapping with the KpnI, Ddel, TaqI, and BamHI endonucleases in order
      to identify the four mutations at the NAT2 gene locus: 481C-->T; 803A-->G; 590G-
      >A and 857G-->A, respectively. RESULTS: In 29 children (60%) various adverse
      effects occurred and in 19 children (40%) no adverse reactions to treatment
      occurred. We found statistically significant differences in the occurrence of the
      identified wt alleles, and alleles with 590A and 857A mutations between the two
      groups of children studied. In the group with adverse effects, 87% of children
      had genotype coding for slow acetylation and only 13% had genotypes containing
      the wt allele. In the group without adverse effects the results were reversed:
      89% had genotypes with the wt allele, and only 2 children (10%) were found to
      have the homozygotic mutation (slow acetylation). CONCLUSION: The results show
      that the occurrence of adverse effects from co-trimoxazole is closely connected
      with the genotype coding for slow acetylation.

PMID- 9923585
TI  - Genetic polymorphism of CYP2D6 in North Indian subjects.
AB  - OBJECTIVES: CYP2D6 polymorphism of clinical relevance occurs with variable
      frequency in different ethnic groups. Since this polymorphism has not been
      studied in a North Indian population, the present study was undertaken. METHODS:
      One hundred healthy unrelated North Indian subjects received 30 mg
      dextromethorphan (DM) orally at bed-time. The amounts of DM and its metabolite,
      dextrorphan (DR), excreted in 8 h urine were estimated by high performance liquid
      chromatography. Metabolic ratio (DM/DR excreted in 8 h) was used as an index of
      the metabolic status of an individual. RESULTS: The analysis of the data by
      frequency distribution histogram, probit and NTV plots demonstrated bimodal
      distribution of the North Indian subjects with respect to hepatic CYP2D6. Out of
      100 subjects, 97 were extensive metabolizers (EMs), whereas three were poor
      metabolizers (PMs). EMs and PMs excreted 29.82 and 2.67 micromol DR (mean value)
      and 2.59 and 8.82 micromol DM (mean value) in 8 h, respectively. MR and log MR
      was 197- and 2.2-fold higher in PMs versus EMs. The antimode value of zero was
      determined by visual observation in frequency distribution histogram and
      inflection point in probit plot. CONCLUSION: From this study, it can be concluded
      that the PM phenotype of CYP2D6 occurs with a frequency of 3% (95% confidence
      interval of 0.33%-6.33%) in North Indians.

PMID- 9923586
TI  - Drug treatment for hypertension in Finnish primary health care.
AB  - OBJECTIVE: To analyse the prescribing patterns of antihypertensive drugs in
      Finnish primary health care and to describe the profiles of monotherapy and
      combination therapy in relation to the duration of high blood pressure. METHODS:
      Thirty out of 250 primary health care centres were randomly selected for the
      study. All doctors (n=337) from the participating health centres recorded all
      hypertensive patients (n=4405) during a 2-week period in May 1995. Adequate
      information was obtained concerning 4294 hypertensives, of whom 65% were women
      with a mean age for the total study population of 64 years. 85% of the patients
      (n=3638) had antihypertensive medication which was classified into five main
      categories: diuretics, beta blocking agents, calcium channel blockers, ACE
      inhibitors and hypotensives. RESULTS: Of the patients using antihypertensive
      medication, 48% were undergoing monotherapy and 52% combination therapy. Beta
      blocking agents were the most frequently prescribed drugs for hypertension, being
      used by half of the patients. ACE inhibitors and diuretics were prescribed in a
      different manner for male and female hypertensives, with men receiving more ACE
      inhibitors and women more diuretics. The number of antihypertensive drugs
      increased with the duration of hypertension, though 38% of the patients having
      hypertension for over 10 years were still undergoing monotherapy. Among patients
      undergoing combination therapy, 75% received two different agents, most often a
      diuretic with a beta blocking agent. CONCLUSIONS: With increasing duration of
      hypertension, the number of antihypertensive drugs also increased. Beta blocking
      agents were the drug of choice for all patients. For women, combination therapy
      more frequently included diuretics, whereas ACE inhibitors were favoured for men.

PMID- 9923587
TI  - The teaching of pharmacology in Italian medical schools: the point of view of
      Italian doctors.
AB  - OBJECTIVE: A survey was carried out to gather the opinions of doctors about the
      current method of teaching pharmacology in Italy. METHODS: A questionnaire was
      mailed to 3860 doctors, who were asked a series of questions regarding the
      teaching of pharmacology to medical students in Italian universities. RESULTS AND
      CONCLUSIONS: The great majority of those who replied considered the teaching they
      received to be mainly theoretical. The doctors thought that much more time and
      attention should be dedicated to those pharmacology subjects that are more
      closely connected to physiopathology and clinical practice (clinical
      pharmacology).

PMID- 9923588
TI  - Skin absorption of Dexamphetamine base--a case report.

PMID- 9923589
TI  - Acetylcholinesterase assay may predict cognitive response of Alzheimer patients
      to eptastigmine treatment.

PMID- 9923590
TI  - Naproxen concentrations in articular tissues after prolonged treatment with
      naproxen sodium in patients with arthritis of the hip.

PMID- 9923591
TI  - Life-threatening vasculitis related to quinidine occurring in a healthy volunteer
      during a clinical trial.

PMID- 9923592
TI  - Hepatitis B core particles as a universal display model: a structure-function
      basis for development.
AB  - Because it exhibits a remarkable capability to accept mutational intervention and
      undergo correct folding and self-assembly in all viable prokaryotic and
      eukaryotic expression systems, hepatitis B core (HBc) protein has been favored
      over other proposed particulate carriers. Structurally, the unusual alpha-helical
      organization of HBc dimeric units allows introduction of foreign peptide
      sequences into several areas of HBc shells, including their most protruding
      spikes. Progress toward full resolution of the spatial structure as well as
      accumulation of chimeric HBc-based structures has brought closer the knowledge
      based design of future vaccines, gene therapy tools and other artificial
      particulate objects.

PMID- 9923593
TI  - Functional reconstitution of RNase P activity from a plastid RNA subunit and a
      cyanobacterial protein subunit.
AB  - The plastid (cyanelle) from the Glaucocystophyceae alga Cyanophora paradoxa
      contains an RNase P RNA subunit (P RNA) similar to the cyanobacterial P RNA. We
      have synthesized this RNA by in vitro transcription and analyzed its activity in
      the absence or presence of the RNase P protein subunit (P protein) from
      Escherichia coli and the cyanobacterium Synechocystis sp. PCC 6803. In contrast
      to the bacterial P RNA, the cyanelle P RNA is not active in the absence of
      protein in any of the conditions tested. A functional enzyme could be
      reconstituted with the Synechocystis protein but not with the E. coli protein.
      This is the first demonstration of RNase P activity reconstitution from
      organellar and bacterial subunits.

PMID- 9923594
TI  - Generalised bilayer perturbation from peptide helix dimerisation at membrane
      surfaces: vesicle lysis induced by disulphide-dimerised melittin analogues.
AB  - The effects of covalent dimerisation of melittin by disulphide formation in
      cysteine-substitution analogues, (melittin K23C)2 and (melittin K23Q,Q25C)2, on
      the kinetics of pore formation in phosphatidylcholine small unilamellar vesicles
      was measured under low ionic strength conditions. The initial rate of melittin
      induced pore formation increased with the square of the peptide concentration,
      whereas both disulphide-dimerised melittin analogues showed a first-order
      dependence of pore formation rates on peptide concentration. These results
      indicate that peptide dimerisation is rate-limiting for pore formation under
      these conditions. A model for a generalised bilayer perturbation resulting from
      the self-association of a pair of peptide helices at the membrane surface is
      proposed which may have implications for a number of biological processes that
      involve the interaction of helical polypeptides with membranes.

PMID- 9923595
TI  - Cell-free production and stable-isotope labeling of milligram quantities of
      proteins.
AB  - We have improved the productivity of an Escherichia coli cell-free protein
      synthesis system. First, creatine phosphate and creatine kinase were used as the
      energy source regeneration system, and the other components of the reaction
      mixture were optimized. Second, the E. coli S30 cell extract was condensed by
      dialysis against a polyethylene glycol solution to increase the rate of
      synthesis. Third, during the protein synthesis, the reaction mixture was dialyzed
      against a low-molecular-weight substrate solution to prolong the reaction. Thus,
      the yield of chloramphenicol acetyltransferase was raised to 6 mg/ml of reaction
      mixture. Stable-isotope labeling of a protein with 13C/15N-labeled amino acids
      for NMR spectroscopy was achieved by this method.

PMID- 9923596
TI  - Mapping of T7 RNA polymerase active site with novel reagents--oligonucleotides
      with reactive dialdehyde groups.
AB  - Oligonucleotides of a novel type containing 2'-O-beta-ribofuranosyl-cytidine were
      synthesized and further oxidized to yield T7 consensus promoters with dialdehyde
      groups. Both types of oligonucleotides were tested as templates, inhibitors, and
      affinity reagents for T7 RNA polymerase and its mutants. All oligonucleotides
      tested retained high affinity towards the enzyme. Wild-type T7 RNA polymerase and
      most of the mutants did not react irreversibly with oxidized oligonucleotides.
      Affinity labeling was observed only with the promoter-containing dialdehyde group
      in position (+2) of the coding chain and one of the mutants tested, namely Y639K.
      These results allowed us to propose the close proximity of residue 639 and the
      initiation region of the promoter within initiation complex. We suggest the
      oligonucleotides so modified may be of general value for the study of protein
      nucleic acid interactions.

PMID- 9923597
TI  - Functional expression of alpha-latrotoxin in baculovirus system.
AB  - To facilitate the study of the mechanism of alpha-latrotoxin action, it is
      necessary to create a biologically active recombinant toxin. Mature alpha
      latrotoxin is naturally produced by post-translational cleavage, probably at two
      furin sites located at the N- and C-termini of the precursor. A recombinant
      baculovirus has now been constructed, which encodes the melittin signal peptide
      fused to the 130-kDa mature toxin between the furin sites. Insect cells, infected
      with this baculovirus, secreted recombinant alpha-latrotoxin. This was partially
      purified and proved indistinguishable from the natural toxin with respect to its
      molecular mass, immunostaining, toxicity to mice, binding to alpha-latrotoxin
      receptors (latrophilin or neurexin Ialpha) and electrophysiological recording in
      the mouse diaphragm. The successful expression of recombinant alpha-latrotoxin
      permits mutational analysis of the toxin.

PMID- 9923598
TI  - Evidence for the co-existence of glutathione reductase and trypanothione
      reductase in the non-trypanosomatid Euglenozoa: Euglena gracilis Z.
AB  - Two NADPH-dependent disulfide reductases, glutathione reductase and trypanothione
      reductase, were shown to be present in Euglena gracilis, purified to homogeneity
      and characterized. The glutathione reductase (Mr 50 kDa) displays a high
      specificity towards glutathione disulfide with a KM of 54 microM. The amino acid
      sequences of two peptides derived from the trypanothione reductase (Mr 54 kDa)
      show a high level of identity (81% and 64%) with sequences of trypanothione
      reductases from trypanosomatids. The trypanothione reductase is able to
      efficiently reduce trypanothione disulfide (KM 30.5 microM) and
      glutathionylspermidine disulfide (KM 90.6 microM) but not glutathione disulfide,
      nor Escherichia coli thioredoxin disulfide, nor 5,5'-dithiobis(2-nitrobenzoate)
      (DTNB). These results demonstrate for the first time (i) the existence of
      trypanothione reductase in a non-trypanosomatid organism and (ii) the coexistence
      of trypanothione reductase and glutathione reductase in E. gracilis.

PMID- 9923599
TI  - Characterization of the bleomycin resistance determinant encoded on the
      transposon Tn5.
AB  - The transposon Tn5 carries a gene, ble, which confers resistance to bleomycin
      (Bm) and gives a survival advantage to its host cell. We found that the ble gene
      product, designated BLMT, is a binding protein with a strong affinity for Bm.
      BLMT quenched both the antibacterial and DNA-cleaving activities of Bm, when
      incubated with the antibiotic. An electron spin resonance spin-trapping analysis
      showed that BLMT inhibits the generation of Bm-induced hydroxyl radical, by
      trapping Bm but not the hydroxyl radical. Western blot analysis using an anti
      BLMT monoclonal antibody revealed that BLMT is immunologically distinct from Bm
      binding proteins from Streptomyces verticillus, Staphylococcus aureus and
      Streptoalloteichus hindustanus. Escherichia coli, transformed with a mutant ble
      having leucine instead of proline at N-terminal amino acid position 7, lost
      resistance to Bm, although the cell maintained the survival benefit. This
      suggests that the Bm resistance mediated by ble is independent of its ability to
      give a survival advantage to the host bacterium.

PMID- 9923600
TI  - The extracellular processing of HIV-1 envelope glycoprotein gp160 by human
      plasmin.
AB  - Cleavage of the envelope glycoprotein precursor gp160 of HIV-1 is a prerequisite
      for the infectivity of HIV-1, and occurs at least in part before gp160 reaches
      the cell surface. Kexin/subtilisin-related endopeptidases are proposed enzyme
      candidates for this intracellular processing. In this study, we reveal the
      possibility that plasminogen binds to the cell surface and part of gp160 escaping
      intracellular processing is cleaved by plasmin extracellularly. Plasmin cleaves
      gp160 precisely at the C-terminal arginine residue of gp120, and the processing
      is effectively inhibited by an analogue peptide of the cleavage motif (RXK/RR)
      and by plasmin inhibitors.

PMID- 9923601
TI  - Impact of the lysine-188 and aspartic acid-189 inversion on activity of trypsin.
AB  - The impact of the charge rearrangement on the specificity of trypsin was tested
      by an inversion of sequence K188D/D189K maintaining the integrity of the charges
      of the substrate binding pocket when switching their polarity. In native trypsin,
      aspartate 189 situated at the bottom of the primary substrate binding pocket
      interacts with arginine and lysine side chains of the substrate. The kinetic
      parameters of the wild-type trypsin and K188D/D189K mutant were determined with
      synthetic tetrapeptide substrates. Compared with trypsin, the mutant K188D/D189K
      exhibits a 1.5- to 6-fold increase in the Km for the substrates containing
      arginine and lysine, respectively. This mutant shows a approximately 30-fold
      decrease of its k(cat) and its second-order rate constant k(cat)/Km decreases
      approximately 40- and 150-fold for substrates containing arginine and lysine,
      respectively. Hence, trypsin K188D/D189K displays a large increase in preference
      for arginine over lysine.

PMID- 9923602
TI  - Regulation of voltage-dependent K+ channels by methionine oxidation: effect of
      nitric oxide and vitamin C.
AB  - Methionine oxidation is known to alter functional properties of a transient A
      type potassium channel expressed in Xenopus oocytes. We show here that nitric
      oxide (NO) slows down the K+ channel inactivation time course by oxidizing a
      critical methionine residue in the inactivation ball domain of the channel
      protein. We also demonstrate that the channel protein is protected from
      methionine oxidation by the enzyme methionine sulfoxide reductase and the
      antioxidant vitamin C.

PMID- 9923603
TI  - Isolation of p-hydroxycinnamaldehyde as an antibacterial substance from the saw
      fly, Acantholyda parki S.
AB  - We purified an antibacterial substance from larvae of the saw fly, Acantholyda
      parki S., and identified its molecular structure as p-hydroxycinnamaldehyde. We
      then synthesized it by reduction of p-hydroxycinnamic acid. The antibacterial
      activity of the synthetic p-hydroxycinnamaldehyde was equal to that of the
      authentic substance. This molecule was found to have a broad antibacterial
      spectrum against not only Gram-negative, but also Gram-positive bacteria.
      Furthermore, it showed antifungal activity against Candida albicans. We suggest
      that this substance may play a role in the defense system of this insect. This is
      the first report of p-hydroxycinnamaldehyde of animal origin.

PMID- 9923604
TI  - Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting
      cells.
AB  - Interleukin-1beta (IL-1beta) is a potent inflammatory cytokine involved in type 1
      diabetes and acts through defined IL-1beta signaling pathways. In the present
      work we describe induction of DNA binding activity to signal transducer and
      activator of transcription (STAT) in response to IL-1beta in clonal insulin
      secreting cells. Moreover, IL-1beta activates a short isoform of STAT-3 that
      potently stimulates transcription. Immunoprecipitation studies reveal an
      interaction between the activated STAT-3 and the IL-1 receptor accessory protein
      indicating an association between the two signaling pathways. This may be a novel
      point of transduction cross talk and an additional mechanism utilised by IL-1beta
      in the pancreatic beta-cell during the process of type 1 diabetes.

PMID- 9923605
TI  - Interferon-gamma inhibits the myofibroblastic phenotype of rat palatal
      fibroblasts induced by transforming growth factor-beta1 in vitro.
AB  - Interferon-gamma (IFN-gamma), a multifunctional cytokine, has been noted as a
      potential therapeutic agent for various fibrotic disorders, including excessive
      scar tissue formation. We previously reported that transforming growth factor
      beta1 (TGF-beta1) induced the myofibroblastic phenotype in palatal fibroblasts
      derived from palatal mucosa, and that such effects might have a close link to
      palatal scar formation. In the present study, we examined the effects of IFN
      gamma on TGF-beta1-pretreated palatal fibroblasts for the purpose of clarifying
      the suppressive potency against myofibroblastic phenotype expression in vitro.
      IFN-gamma significantly altered the spindle morphology of TGF-beta1-pretreated
      palatal fibroblasts into the polygonal one that was similar to the non-treated
      palatal fibroblasts. This change was parallel with a decrease in the expression
      of alpha-smooth muscle actin protein, a marker for myofibroblast, as determined
      by immunoblot analysis. Northern blot analysis showed that IFN-gamma inhibited
      proalpha2(I) collagen mRNA expression that was stimulated by TGF-beta1
      pretreatment for 24 h. Furthermore, IFN-gamma decreased the cell contractility
      enhanced by TGF-beta1 pretreatment for 24 h in a three-dimensional collagen gel
      culture system. These results suggest that IFN-gamma may have negative effects
      with regard to controlling the myofibroblastic phenotype induced by TGF-beta1 in
      palatal fibroblasts.

PMID- 9923606
TI  - Generation of hydrogen peroxide precedes loss of mitochondrial membrane potential
      during DNA alkylation-induced apoptosis.
AB  - Pulsed field gel electrophoresis showed that the initiation time of DNA breakage
      induced by the DNA alkylating agent duocarmycin A, which is not a redox-cycling
      agent, was almost the same in the human leukemia cell line HL-60 and its H2O2
      resistant clone HP100. Catalase activity of HP100 cells was much higher than that
      of HL-60 cells. Duocarmycin A-mediated DNA ladder formation in HP100 cells was
      delayed compared with that in HL-60 cells, suggesting the involvement of H2O2 in
      duocarmycin A-induced apoptosis. Flow cytometry demonstrated that peroxide
      formation preceded loss of mitochondrial membrane potential (delta psi m) in
      cells treated with duocarmycin A. Then, caspase-3 was activated, followed by DNA
      ladder formation. These findings suggest that DNA damage by duocarmycin A induces
      H2O2 generation, which causes delta psi m loss and subsequently caspase-3
      activation, resulting in apoptosis.

PMID- 9923607
TI  - The role of subunit composition on prepulse facilitation of the cardiac L-type
      calcium channel.
AB  - Facilitation of calcium current by depolarizing prepulses has been observed in
      many cells including cardiac muscle. The mechanism underlying prepulse
      facilitation is controversial with respect to the requirements of channel
      subunits and cAMP kinase. We found that coexpression of the cardiac alpha1C-a
      subunit with the cardiac beta2a subunit significantly promotes the facilitation
      of I(Ba) by strong depolarizing prepulses. The magnitude of I(Ba) facilitation
      depended on the voltage potential of the prepulse and the interval duration
      between prepulse and test pulse. Prepulse facilitation was not affected by
      coexpression of AKAP79 and conditions favoring cAMP-dependent phosphorylation.
      Prepulse facilitation was also observed in cells expressing an alpha1C-a subunit
      which was truncated at residue 1733 removing the cAMP kinase site at Ser-1928.
      Facilitation was abolished by coexpression of the alpha2delta-1 or alpha2delta-3
      subunit. We conclude that the expressed alpha1C-a beta2a complex is sufficient to
      support prepulse facilitation. Facilitation is prevented by coexpression of the
      alpha2delta subunit.

PMID- 9923608
TI  - In vitro assembly of a beta2 cytochrome b559-like complex from the chemically
      synthesised beta-subunit encoded by the Synechocystis sp. 6803 psbF gene.
AB  - The alpha- and beta-subunits of cytochrome b559 encoded by the psbE and psbF
      gene, respectively, are essential components of photosystem II. The exact
      structure of this cytochrome is not yet known. The beta-subunit of the
      Synechocystis sp. 6803 cytochrome b559 complex was synthesised by means of solid
      phase peptide synthesis. Under reducing conditions, two beta-peptide molecules
      could be assembled specifically with one haem to form a beta2 cytochrome b559
      like complex. The spectral properties and the midpoint redox potential (48+/-5
      mV) of the in vitro assembled beta2 cytochrome are nearly identical to those of
      the low potential form of the native cytochrome b559.

PMID- 9923609
TI  - Determination of the distance between Y(Z)ox* and QA-* in photosystem II by
      pulsed EPR spectroscopy on light-induced radical pairs.
AB  - Out-of-phase electron spin echo envelope modulation (ESEEM) spectroscopy was used
      to determine the distances within two consecutive radical pair states initiated
      by a laser flash in photosystem II membrane fragments at pH 11. The distance
      between the spin density centers of the primary electron donor cation radical,
      P680+*, and the reduced plastoquinone acceptor, QA-*, has been found to be 27.7+/
      0.7 A in agreement with previous results. Near room temperature and at high pH,
      P680+* is reduced by Y(Z), a redox active tyrosine residue, on a sub-microsecond
      timescale. As a consequence, the subsequent radical pair state, Y(Z)ox*-QA-*,
      could be investigated after almost complete reduction of P680+* by Y(Z). The
      determined dipolar electronic spin-spin coupling within the radical pair
      Y(Z)ox*QA-* corresponds to a distance of 34+/-1 A between the two molecules.

PMID- 9923610
TI  - Identification and cloning of a novel cellular protein Naf1, Nef-associated
      factor 1, that increases cell surface CD4 expression.
AB  - The nef gene of human and simian immunodeficiency virus is a key factor in
      acquired immunodeficiency syndrome pathogenesis and virus replication. Several
      Nef-induced phenomena, including the down-regulation of CD4 molecule, have been
      previously reported. In this study, we have identified and cloned a novel
      cellular protein Naf1 (Nef-associated factor 1), which associated with Nef in the
      yeast two-hybrid system and pull-down assay. The Naf1 gene generates two isoforms
      (Naf1alpha and beta) containing four coiled-coil structures. The Naf1 mRNA is
      ubiquitously expressed in human tissues with strong expression in peripheral
      blood lymphocytes and spleen. Naf1 overexpression increased cell surface CD4
      expression. Nef suppressed this Naf1-induced augmentation of CD4 expression,
      providing a novel mode of Nef action in CD4 down-regulation.

PMID- 9923611
TI  - Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy,
      inhibit the proinflammatory transcription factor NF-kappaB.
AB  - Activation of transcription factor NF-kappaB is elevated in several chronic
      inflammatory diseases and is responsible for the enhanced expression of many
      proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica
      dioica) are used as antiinflammatory remedies in rheumatoid arthritis.
      Standardized preparations of these extracts (IDS23) suppress cytokine production,
      but their mode of action remains unclear. Here we demonstrate that treatment of
      different cells with IDS23 potently inhibits NF-kappaB activation. An inhibitory
      effect was observed in response to several stimuli, suggesting that IDS23
      suppressed a common NF-kappaB pathway. Inhibition of NF-kappaB activation by
      IDS23 was not mediated by a direct modification of DNA binding, but rather by
      preventing degradation of its inhibitory subunit IkappaB-alpha. Our results
      suggests that part of the antiinflammatory effect of Urtica extract may be
      ascribed to its inhibitory effect on NF-kappaB activation.

PMID- 9923612
TI  - Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast
      Pichia pastoris can stimulate neurite outgrowth.
AB  - The human amyloid precursor-like protein 2 (APLP2) is a member of the Alzheimer's
      disease amyloid precursor protein (APP) gene family. The human APLP2 ectodomain
      (sAPLP2) was expressed in the yeast Pichia pastoris and the recombinant sAPLP2
      was purified from the culture medium in a single step by metal-chelating
      Sepharose chromatography. The neuritotrophic activity of APLP2 was compared to
      the APP isoforms sAPP695 and sAPP751 on chick sympathetic neurones. APLP2 had
      neurite outgrowth-promoting activity similar to that of the APP isoforms. This
      suggests that APP and APLP2 have a similar or related role and supports the idea
      of a redundancy in function between the APP-gene family proteins.

PMID- 9923613
TI  - The human and rat forms of multiple inositol polyphosphate phosphatase:
      functional homology with a histidine acid phosphatase up-regulated during
      endochondral ossification.
AB  - We have derived the full-length sequences of the human and rat forms of the
      multiple inositol polyphosphate phosphatase (MIPP); their structural and
      functional comparison with a chick histidine acid phosphatase (HiPER1) has
      revealed new information: (1) MIPP is approximately 50% identical to HiPER1, but
      the ER-targeting domains are divergent; (2) MIPP appears to share the catalytic
      requirement of histidine acid phosphatases, namely, a C-terminal His residue
      remote from the RHGxRxP catalytic motif; (3) rat MIPP mRNA is up-regulated during
      chondrocyte hypertrophy. The latter observation provides a context for proposing
      that MIPP may aid bone mineralization and salvage the inositol moiety prior to
      apoptosis.

PMID- 9923614
TI  - Cloning, sequencing and functional expression of a novel human thioredoxin
      reductase.
AB  - The DNA sequence encoding a novel human thioredoxin reductase has been
      determined. The protein is predicted to have 524 amino acids including a
      conserved -Cys-Val-Asn-Val-Gly-Cys catalytic site and a selenocysteine containing
      C-terminal -Gly-Cys-SeCys-Gly. The predicted molecular mass is 56.5. The newly
      identified TR sequence exhibits 54% identity to a previously reported human
      thioredoxin reductase and 37% identity to human glutathione reductase. Transient
      transfection of human embryonal kidney cells results in a 5-fold increase in
      thioredoxin reductase activity but no increase in glutathione reductase activity.

PMID- 9923615
TI  - A novel mouse beta defensin, Defb2, which is upregulated in the airways by
      lipopolysaccharide.
AB  - Studies have shown that beta defensins are present in the human airways and may
      be relevant to the pathogenesis of cystic fibrosis lung disease. Here we report
      the identification of a novel mouse gene, Defb2, which shows sequence similarity
      to previously described mouse and human airway beta defensins. Defb2 does not
      appear to be expressed in the airways of untreated mice but it is upregulated in
      response to lipopolysaccharide. The induced expression of this gene by an
      inflammatory stimulus strongly suggests that this defensin contributes to host
      defence at the mucosal surface of the airways.

PMID- 9923617
TI  - Quality control of culture media--perspectives and problems.
AB  - The Working Party on Culture Media (WPCM) of the International Union of
      Microbiological Societies (IUMS) has promoted and facilitated the development of
      methods for quality control of culture media used for the detection and
      enumeration of food-borne microorganisms since the early 1980s. While progress
      has been made in establishing protocols to test for productivity and selectivity
      of media, problems associated with the influence of food constituents and
      background microflora, as well as the presence of sublethally injured cells in
      test foods, are yet to be fully addressed before optimum methods for assessing
      the quality of media can be defined. However, for various reasons, the
      development of standardised procedures which account for the influence of food
      constituents or state of debilitation of target microorganisms may not be
      practical or even desirable.

PMID- 9923618
TI  - Quality assurance in food microbiology--a novel approach.
AB  - The introduction of quality systems as a requirement of laboratory accreditation
      is causing microbiologists to review current practices. The need for Quality
      Assurance (QA) in food microbiology is of growing importance and this paper
      presents a novel approach to implementing QA based on a system which is analogous
      to the Hazard Analysis Critical Control Point approach adopted by the food
      industry. The basis of the QA system is the recognition of Quality Assessment
      Points (QAPs). Several Quality Control and monitoring practices are suggested for
      each of the QAPs with the overall aim of developing a Total Quality Assurance
      system for food microbiology laboratories.

PMID- 9923616
TI  - Non-specific effects of methyl ketone peptide inhibitors of caspases.
AB  - Caspases are a family of cysteine proteases which play a crucial role in
      apoptosis and inflammation. The involvement of caspases in these processes can be
      demonstrated by their irreversible inhibition with fluoromethyl ketone and
      chloromethyl ketone derivatives of peptides resembling the cleavage site of known
      caspase substrates. These inhibitors irreversibly alkylate the cysteine residue
      in the active site of caspases. In this study we show that a biotinylated
      fluoromethyl ketone peptide inhibitor of caspases (z-VAD.fmk) also efficiently
      affinity-labeled cathepsin B and cathepsin H. In addition, the caspase inhibitors
      z-VAD.fmk, z-DEVD.fmk and Ac-YVAD.cmk also efficiently inhibited cathepsin B
      activity in vitro and in tissue culture cells at concentrations that are
      generally used to demonstrate the involvement of caspases.

PMID- 9923619
TI  - Development of standard methods with special reference to Europe.
AB  - For a long time, many different microbiological methods were used around the
      world in order to enumerate or detect contaminants in foods. The development of
      commercial, but also scientific and technical exchanges between countries has
      stimulated new developments and a desire to harmonize methods. The example of
      AFNOR (French Association for Standardization) is first presented. Then, the new
      developments under CEN (European Committee for Standardization) are described,
      emphasizing a Measurements and Testing project. The MicroVal project, now
      integrated as a task force within CEN Technical Committee 275/Working Group 6 is
      described. Finally, the possibility of working towards an international consensus
      through the Codex Alimentarius is discussed.

PMID- 9923620
TI  - MicroVal: a European approach to the certification of new microbiological
      methods. MicroVal secretariat.
AB  - Reference methods, such as those published by ISO (International Standards
      Organisation), are often laborious, expensive, and time consuming. More
      convenient, cheaper and more rapid methods are therefore often preferred for
      daily use. However, results obtained with such methods should be accepted by
      official control laboratories and trade partners, MicroVal, a European project
      for the validation and approval of alternative methods for the microbiological
      analysis of food and beverages, was set up to achieve this. A description is
      given of MicroVal. The general rules and certification procedures are described,
      as well as how the certification is organised. MicroVal aims at certifying
      alternative methods, i.e. methods which perform as well as internationally
      standardised methods. Whenever possible, an ISO standard method is used as the
      reference. Certification of alternative methods should ensure their acceptance by
      governmental inspection laboratories and laboratories in the food trade, thus
      facilitating commerce within the European Union.

PMID- 9923621
TI  - AOAC validation of qualitative and quantitative methods for microbiology in
      foods. Association of Official Agricultural Chemists.
AB  - The purpose of AOAC International is promoting quality measurements and methods
      validation in the analytical sciences. The actual work of developing and testing
      methods is done by a network of AOAC members and volunteers. Validation of the
      methods is established by the AOAC Official Methods Program. The objective of
      this program is to provide analytical methods for which performance
      characteristics have been validated to the highest degree of confidence through
      an independent, multiple laboratory collaborative study. The performance
      characteristics for quantitative microbiological methods include repeatability,
      reproducibility and critical relative difference, while the characteristics for
      qualitative methods are sensitivity and specificity. The Official Methods Program
      is illustrated by a practical example of a collaborative study through which
      salmonella detection by motility enrichment on Modified Semi-solid Rappaport
      Vassiliadis (MSRV) medium was adopted as an Official Method.

PMID- 9923622
TI  - Strategies in the development of media for the detection of food-borne pathogens.
AB  - Successful medium development is dependent on using a systematic approach and
      also by giving due consideration to the factors which can influence the
      performance of the medium at the various stages of assessment. The most important
      factors to be considered are: (i) the properties of the target organisms, (ii)
      the selection of test strains, (iii) the methods of evaluation, (iv) the basal
      medium and growth supplements, (v) the properties of the medium, and (vi) the
      intended use of the medium. If these are investigated fully then culture media
      can be optimised to fulfil the demands of modem microbiology techniques used for
      detection and confirmation of bacteria.

PMID- 9923623
TI  - The use of reference materials in quality assurance programmes in food
      microbiology laboratories.
AB  - Nine different reference materials (RMs) for use in food and water microbiology
      have been developed with the support of the European Commission (EC). The
      production process of RMs is based on spray drying bacteria suspended in milk.
      The highly contaminated milk powder (HCMP) obtained is mixed with sterile milk
      powder to achieve the desired level of contamination and is subsequently filled
      into gelatine capsules. The HCMP may need to be stabilised by storage for more
      than a year before a stable RM can be prepared. The HCMP are mixed with sterile
      milk powder using a pestle and mortar in order to produce homogeneous RMs. For
      routine use of RMs Shewhart control charts can be produced. Based on log10
      transformed counts, control limits are calculated. Rules for the interpretation
      of results facilitate the detection of out of control situations. Besides RMs
      there are also CRMs (Certified Reference Materials) that are certified by the EC
      Community Bureau of Reference (BCR) and are intended for occasional use. Based on
      the BCR certificate, user tables are produced presenting the 95% confidence
      limits for the number of capsules likely to be examined in practice. Also power
      analysis is made to indicate the minimum difference between the certified value
      and the observed geometric mean value in relation to the number of capsules
      examined.

PMID- 9923624
TI  - Update on media for isolation of Enterobacteriaceae from foods.
AB  - Testing for 'total' Enterobacteriaceae, coliforms and Escherichia coli as marker
      organisms in foods and detection of specific pathogens of the family
      Enterobacteriaceae, including pathogenic E. coli, Salmonella, Shigella and
      Yersinia spp. is widely applied in many food control laboratories. This review
      describes some recent developments in culture media for these organisms. Methods
      for enumeration of E. coli include the standard MPN technique, a membrane-filter
      method and the use of media containing chromogenic and fluorogenic indicators for
      beta-D-glucuronidase (GUD) activity. Shiga toxin-producing E. coli O157 strains
      usually do not ferment sorbitol and are GUD-negative. These characteristics are
      used in selective media for these organisms, such as cefixime tellurite sorbitol
      MacConkey agar. For the detection of salmonellae, motility enrichment in Modified
      Semisolid Rappaport-Vassiliadis (MSRV) medium shows equal or better results than
      the use of standard Rappaport-Vassiliadis broth. Addition of nitrofurantoin to
      diagnostic semisolid salmonella agar and to xylose lysine desoxycholate agar
      favours the isolation of S. enteritidis. Recently developed salmonella media use
      different selective and diagnostic properties, such as acid formation from
      propylene glycol, glucuronate fermentation, fermentation of glycerol and addition
      of Tergitol 4 as selective agent. The isolation of Shigella spp. from foods is
      rather difficult and further evaluation of suggested isolation systems and the
      development of more effective methods for the isolation of this pathogen are
      needed. Yersinia enterocolitica includes both pathogenic and nonpathogenic
      biotypes and serogroups. As no single procedure will recover all pathogenic
      strains of Y. enterocolitica, the use of two isolation procedures in parallel is
      recommended.

PMID- 9923625
TI  - Proficiency testing schemes--their role in quality assurance.

PMID- 9923626
TI  - The working party on culture media (WPCM).

PMID- 9923627
TI  - A formal system of approval for monographs in the pharmacopoeia of culture media-
      statement from the IUMS-ICFMH working party on culture media.
AB  - A categorization system for monographs on culture media is outlined which will
      lead to more rapid publication and a formal division into three classifications;
      draft, proposed and approved. This should assist the quality assurance and
      accreditation processes in food microbiology laboratories.

PMID- 9923628
TI  - A new expression for selectivity of liquid and solid media--statement from the
      IUMS-ICFMH working party on culture media.

PMID- 9923629
TI  - Monographs published by the IUMS-ICFMH working party on culture media.

PMID- 9923630
TI  - Immunoregulation of experimental autoimmune encephalomyelitis: editorial
      overview.

PMID- 9923631
TI  - Antigen-driven regulation of experimental autoimmune encephalomyelitis.

PMID- 9923632
TI  - Cytokines as intrinsic and exogenous regulators of pathogenesis in experimental
      autoimmune encephalomyelitis.

PMID- 9923633
TI  - Immune cell entry to the CNS--a focus for immunoregulation of EAE.
AB  - T-cell-derived cytokines are therefore individually unnecessary and collectively
      insufficient for microglial response. This somewhat provocative interpretation
      does not exclude a role for T-cell cytokines in induction of a microglial
      response in EAE, but it may be easier to show a non-requirement then to prove
      such a role. The point that emerges is that cytokine production in the CNS
      parenchyma is itself dependent on the prior infiltration of immune cells, and
      that without immune cell entry, EAE does not occur. This identifies events at the
      BBB, and in particular in the perivascular space, as critical immunoregulatory
      events in development and progression of EAE.

PMID- 9923634
TI  - Chemokine regulation of CNS T-cell infiltration in experimental autoimmune
      encephalomyelitis.

PMID- 9923635
TI  - Cytokines and antibodies in myelin oligodendrocyte glycoprotein-induced
      experimental allergic encephalomyelitis.

PMID- 9923636
TI  - Tumour necrosis factor-alpha and lymphotoxin-alpha in the pathology of
      experimental autoimmune encephalomyelitis: is either one responsible or is there
      another ligand-mediating disease?

PMID- 9923637
TI  - The comeback of the elusive "suppressor" cell: an update on the regulatory
      network in EAE.

PMID- 9923638
TI  - Bystander suppression in experimental autoimmune encephalomyelitis: where and how
      does it occur?

PMID- 9923639
TI  - TCR peptide-reactive T cells and peripheral tolerance to myelin basic protein.

PMID- 9923640
TI  - T-cell design: optimizing the therapeutic potential of autoreactive T cells by
      genetic modification.
AB  - Autoreactive CD4+ Th2 cells have been shown to be therapeutic in the treatment of
      EAE. However, their full therapeutic potential has yet to be realized. Genetic
      modification of autoreactive Th2 T cells may provide the means for delivering
      therapeutic transgene factors to autoimmune inflammatory lesions. Optimum
      therapeutic effects may be achieved by designing Th2 T cells in such a way that
      expression of transgene factors is regulated by antigen-inducible IL4, IL5 or
      IL10 transgene promoters. The innate antiinflammatory effects of the native
      autoreactive Th2 T cell may be enhanced by incorporating transgene regenerative
      growth factors in the T-cell design. Such factors may include remyelination
      growth factors (PDGF-A, bFGF, and IGF-I) that complement each other by acting
      predominantly at different stages in the development of mature myelinating
      oligodendrocytes. Moreover, in light of recent findings indicating extensive
      axonal damage during MS, neuroprotective transgene factors may prove to be
      therapeutic when delivered to EAE lesions by autoreactive Th2 T cells. Thus,
      optimum therapeutic effects may require multiple transfers of autoreactive Th2 T
      cells producing several distinct complementary transgene factors. In addition,
      the pathogenicity of epitope spreading and the inherent instability of self
      recognition during EAE may require serial transfer of genetically modified T
      cells reacting to multiple self determinants.

PMID- 9923641
TI  - Peptide binding and editing: generation of TCR ligands.

PMID- 9923642
TI  - Signalling through the TCR.

PMID- 9923643
TI  - Antigen receptors in lymphoid cell development and lymphocyte activation.

PMID- 9923644
TI  - Th1 and Th2 cells.

PMID- 9923645
TI  - Pathogenic and protective T-cell responses in autoimmune diseases.

PMID- 9923646
TI  - Pathogenic and protective responses in parasitic infections.

PMID- 9923647
TI  - Protective T-cell responses against tumours.

PMID- 9923648
TI  - Cellular and extracellular biology of the latent transforming growth factor-beta
      binding proteins.
AB  - The latent transforming growth factor-beta binding proteins (LTBP) are a recently
      identified family of widely expressed multidomain glycoproteins that range in
      size from 125 kDa to 240 kDa. Four LTBP genes have been described, and the
      homology of latent transforming growth factor-beta binding proteins molecules to
      the fibrillins has resulted in their inclusion in the so-called 'fibrillin
      superfamily'. They form intracellular covalent complexes with latent transforming
      growth factor-beta and target these growth factors to the extracellular matrix.
      This review describes their structure, summarizes current understanding of their
      dual roles as growth factor binding proteins and components of the extracellular
      matrix, and highlights their significance in tissue development and disease.

PMID- 9923649
TI  - Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by tumor promoter
      okadaic acid is mediated by stress-activated protein kinases Jun N-terminal
      kinase and p38.
AB  - Collagenase-1 (matrix metalloproteinase-1, MMP-1) is expressed by several types
      of cells, including fibroblasts, and apparently plays an important role in the
      remodeling of collagenous extracellular matrix in various physiologic and
      pathologic situations. Here, we have examined the molecular mechanisms of the
      activation of fibroblast MMP-1 gene expression by a naturally occurring non
      phorbol ester type tumor promoter okadaic acid (OA), a potent inhibitor of
      serine/threonine protein phosphatase 2A. We show that in fibroblasts OA activates
      three distinct subgroups of mitogen activated protein kinases (MAPKs):
      extracellular signal-regulated kinase1,2 (ERK1,2), c-Jun N-terminal-kinase/stress
      activated protein kinase (JNK/SAPK) and p38. Activation of MMP-1 promoter by OA
      is entirely blocked by overexpression of dual-specificity MAPK phosphatase CL100.
      In addition, expression of kinase-deficient forms of ERK1,2, SAPKbeta, p38, or
      JNK/SAPK kinase SEK1 strongly inhibited OA-elicited activation of MMP-1 promoter.
      OA-elicited enhancement of MMP-1 mRNA abundance was also strongly prevented by
      two chemical MAPK inhibitors: PD 98059, a specific inhibitor of the activation of
      ERK1,2 kinases MEK1,2; and SB 203580, a selective inhibitor of p38 activity.
      Results of this study show that MMP-1 gene expression in fibroblasts is
      coordinately regulated by ERK1,2, JNK/SAPK, and p38 MAPKs and suggest an
      important role for the stress-activated MAPKs JNK/SAPK and p38 in the activation
      of MMP-1 gene expression. Based on these observations, it is conceivable that
      specific inhibition of stress-activated MAPK pathways may serve as a novel
      therapeutic target for inhibiting degradation of collagenous extracellular
      matrix.

PMID- 9923650
TI  - Hyperhomocysteinemia induces elastolysis in minipig arteries: structural
      consequences, arterial site specificity and effect of captopril
      hydrochlorothiazide.
AB  - Hyperhomocysteinemia is a risk factor for arterial diseases, and the
      deterioration of the arterial elastic structures is one of the possible
      mechanisms underlying this epidemiological association. The aim of this paper is
      to quantitatively characterize such structural alterations and to explore their
      causes in a previous model of dietary induced mild hyperhomocysteinemia in
      minipigs. After four months, both a morphodensitometrical analysis of the elastic
      structure and a biochemical analysis of elastin and elastase activities were
      performed on the infrarenal abdominal aorta (IRAA) and the proximal left
      interventricular coronary artery (LIVCA) of control (C), hyperhomocysteinemic (H)
      and captopril-hydrochlorothiazide (Cp-Htz, 25 + 12.5 mg/d)-treated (H+/-Cp)
      minipigs (n = 8/group). Hyperhomocysteinemia was found to induce an increase in
      parietal elastolytic metalloproteinase activities. It resulted in opening and
      enlargement of fenestrae through the medial elastic laminae and in a decrease in
      medial elastin content (p < 10(-3)), expressed as well as volume density (%) as
      weight concentration (microg elastin/mg dry tissue). The thickness of the media
      and its basic lamellar organization was unchanged. The reduction in volume
      density was more dramatic in LIVCA (H: 4.7 +/- 0.9 vs C: 8.8 +/- 2.4), where it
      was evenly distributed within the media, than in IRAA (H: 6.7 +/- 1.1 vs C: 9.3
      +/- 1.2), where the deep medial layers were less affected. Cp-Htz partly
      prevented the hyperhomocysteinemia-induced reduction of the medial elastin
      content in LIVCA (5.7 +/- 1.2) and IRAA (7.9 +/- 1.4). This effect, occurring in
      the subintimal layers of the media in both arteries but not in the deeper layers,
      resulted in a less beneficial effect in LIVCA than in IRAA. This result parallels
      the moderate beneficial therapeutic effect of ACE inhibitors against coronary
      atherosclerosis in humans. This paper reports for the first time a quantitative
      analysis of the arterial site-dependent deterioration of the elastic structure
      caused by mild hyperhomocysteinemia and the involvement of metalloproteinases in
      this process. These results confirm that the plaque-independent damage to elastic
      structure previously described in hyperhomocysteinemic-atherosclerotic minipigs
      was mainly due to homocysteine. This highlights that the metalloproteinase
      related elastolysis and the subsequent structural deterioration is one of the
      major events underlying the epidemiological association between mild
      hyperhomocysteinemia and arterial diseases.

PMID- 9923651
TI  - An alpha2(I) glycine to aspartate substitution is responsible for the presence of
      a kink in type I collagen in a lethal case of osteogenesis imperfecta.
AB  - Type I collagen synthesized by cultured skin fibroblasts was analyzed
      biochemically and molecularly to characterize the defect in a patient affected by
      lethal Osteogenesis Imperfecta. The SDS-Urea-PAGE of procollagen and collagen
      revealed a broad alpha1(I) band, a normal alpha2(I) and another alpha2(I) band
      migrating equidistant between alpha1 and alpha2. When synthesized in the presence
      of alphaalpha'-dipyridyl, an inhibitor of prolyl and lysyl hydroxylation,
      procollagen and collagen of media and cell layers contained both normal and
      slower alpha2(I), but only normal alpha1(I). The persistence of the two forms of
      alpha2(I) chains suggested a mutation in a COL1A2 gene. CNBr cleavage of collagen
      yielded overmodified alpha1(I) CB3 and CB7 peptides and delayed migration of the
      alpha2(I) CB3-5 peptide. A delayed CB3-5 was also found after alpha,alpha'
      dipyridyl treatment. These data localized the mutation between aa 353 and 551 in
      alpha2(I) (CB3-5). Sequencing the subcloned alleles in this region revealed a G-
      >A transition at nt 1671 in one allele, changing Gly 421 to Asp in an alpha2(I)
      chain. The mutation was demonstrated to occur on the paternally derived allele,
      using a common C-->A polymorphism at alpha2(I) nt 1585 and by the presence of a
      rare variant, Arg618-->Gln (Phillips et al., 1990), in the paternal genomic DNA
      and the proband's mutant allele. Procollagen processing was normal. The Tm of the
      slow alpha2(I) collagen was 2 degrees C lower than the control, indicating
      decreased triple helix stability. Mutant collagen was incorporated in the
      extracellular matrix deposited by cultured fibroblasts. The dramatic delay in
      alpha2(I) electrophoretic mobility must be induced by the Gly-->Asp substitution,
      since the Arg-->Gln variant causes only mild electrophoretic delay. Substantial
      delay in gel mobility even in the absence of overmodification suggested the
      presence of a kink in the mutated alpha2(I) chains. Rotary shadowing electron
      microscopy of secreted fibroblast procollagen confirmed the presence of a kink in
      the region of the helix containing the glycine substitution. The kinking of the
      collagen helix occurs in the absence of dimer formation. Kinking may interfere
      with normal helix folding, as well as with the interactions of collagen fibrils
      with the collagenous and non-collagenous extracellular matrix proteins.

PMID- 9923652
TI  - New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction
      in rheumatoid arthritis: destruction from above.
AB  - Our aim was to investigate the collagenolytic potential and localization of
      matrix metalloproteinase-2 (MMP-2) in relation to its regulatory proteins
      membrane type MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) in
      rheumatoid arthritis (RA). For this purpose, we have used purification of MMP-2,
      MMP-8, MMP-9 and interstitial type I, II and III collagens; SDS
      PAGE/densitometric collagenase activity assay; zymography; Western blotting;
      reverse transcriptase polymerase chain reaction; in situ hybridization; and
      immunofluorescence, ABC, ABC-APAAP double immunostainings. MMP-2 degraded human
      type II collagen almost as effectively as MMP-8, whereas MMP-9 did not cleave
      type II collagen. In synovial tissue, MT1-MMP, TIMP-2 and MMP-2 were found in
      synovial lining in fibroblast- and macrophage-like cells, in stromal cells and in
      vascular endothelium. MT1-MMP, TIMP-2 and MMP-2 were strongly expressed in the
      pannocytes of the invasive pannus at the interface, but staining was weak and/or
      there were few positive cells both "above" and "below" the soft-to-hard tissue
      (cartilage and/or bone) interface. Rheumatoid synovial tissue extract contained
      proteolytically active 62/59 kDa MMP-2 and 43 kDa MT1-MMP, but no free TIMP-2.
      These results indicate that components of the ternary MT1-MMP/TIMP-2/MMP-2
      complex are coexpressed in the normal synovial lining and in its pathological
      extension on the hyaline articular cartilage. MMP-2 may participate in the
      remodeling of the normal lining and also seems to be localized/focalized to
      pannocytes at a site critical for tissue destruction in arthritis.

PMID- 9923653
TI  - Laminin 5 can promote assembly of the lamina densa in the skin equivalent model.
AB  - Skin equivalents were prepared by culturing human keratinocytes on the surface of
      type I collagen gel contracted by human skin fibroblasts (dermal equivalents) and
      by raising the gel to an air-liquid interface. A stratified squamous epithelium
      was formed with a well-differentiated cornified layer at the top of keratinocyte
      layers within 7 days after plating of the keratinocytes on the dermal
      equivalents. Although major basement membrane components such as collagens IV and
      VII and laminin 5 were detected immunohistochemically at the dermal-epidermal
      junction, a lamina densa was rarely observed by electron microscopy even in 14
      day skin equivalents. When laminin 5 (1, 5 or 20 microg/ml) was added to the
      culture medium on day 7 through day 14, types IV and VII collagens at the dermal
      epidermal junction stained more strongly by immunohistochemistry compared with
      the control. Patches of lamina densa were present along the epidermal-dermal
      junction, and vesicles containing electron-opaque sheets approximately 0.6 microm
      in diameter that reacted with anti-collagen IV antibody were also observed in
      basal keratinocytes in 14-day skin equivalents by electron microscopy.
      Morphometric analysis showed that the total length of lamina densa along the
      dermal-epidermal junction as well as in the vesicles increased up to 180%, 230%
      or 520% of control cultures by the addition of laminin 5 (1, 5 or 20 microg/ml,
      respectively). These results suggest that laminin 5 accelerates formation of the
      lamina densa along the dermal-epidermal junction of the skin equivalents,
      depending on the concentration of laminin 5 supplemented exogenously.

PMID- 9923654
TI  - Regulation of osteopontin gene expression during egg shell formation in the
      laying hen by mechanical strain.
AB  - The aim of this study is to evaluate the regulation of the osteopontin (OPN) gene
      expression by non-hormonal stimuli, such as calcium flux and mechanical strain
      during the daily egg cycle in the oviduct of the laying hen. After the egg enters
      the eggshell gland (ESG), the OPN gene is expressed by the epithelium cells in
      two waves: first by the basal cells and only then by the apical cells of the
      epithelium. A reduction in OPN gene expression was observed 1 h prior to laying.
      The calbindin gene, which marks the onset of calcification, was found to be
      expressed in the glandular epithelium starting 2 h after OPN gene expression. In
      addition, the formation of soft shells was accompanied by a reduction in
      calbindin, but not in OPN, gene expression. The application of a mechanical
      strain comparable to that induced by an egg led to induction of OPN gene
      expression at a normally quiescent phase in the cyclical expression of this gene.
      The induction of the gene was time- and strain-dependent and temporally similar
      to that induced by the entry of the egg into the ESG. In contrast, the calbindin
      gene was not affected by mechanical strain. The ESG of the laying hen provides a
      system to study the effect of a mechanical strain on matrix protein production in
      vivo, in a relevant physiological setting. The finding suggests that, in contrast
      to calbindin, OPN gene expression is not regulated by calcium flux but rather by
      the mechanical strain imposed by the resident egg.

PMID- 9923655
TI  - Retention of cartilage oligomeric matrix protein (COMP) and cell death in
      redifferentiated pseudoachondroplasia chondrocytes.
AB  - Cartilage oligomeric matrix protein (COMP) is a large extracellular glycoprotein
      that is found in the territorial matrix surrounding chondrocytes. Two skeletal
      dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1)
      are caused by mutations in the calcium binding domains of COMP. In this study, we
      identified two PSACH mutations and assessed the effect of these mutations on
      redifferentiated chondrocyte structure and function. We confirmed, in vitro, that
      COMP is retained in enormous cisternae of the rough endoplasmic reticulum (rER)
      and relatively absent in the PSACH matrix. The rER accumulation may compromise
      chondrocyte function, leading to chondrocyte death. Moreover, while COMP appears
      to be deficient in the PSACH matrix, the matrix appeared to be normal but the
      over-all quantity was reduced. These results suggest that the abnormality in
      linear growth in PSACH may result from decreased chondrocyte numbers which would
      also affect the amount of matrix produced.

PMID- 9923656
TI  - Identification of chicken and C. elegans fibulin-1 homologs and characterization
      of the C. elegans fibulin-1 gene.
AB  - Fibulin-1, a member of the emerging family of fibulin proteins, is a component of
      elastic extracellular matrix fibers, basement membranes and blood. Homologs of
      fibulin-1 have been described in man, mouse and zebrafish. In this study, we
      describe the isolation and sequencing of chicken fibulin-1C and D cDNA variants.
      We also describe identification of a C. elegans cDNA encoding fibulin-1D and
      cosmids containing the C. elegans fibulin-1 gene. Using the cDNA, RT-PCR and
      computer-based analysis of genomic sequences, the exon/intron organization of the
      C. elegans fibulin-1 gene was determined. The C. elegans fibulin-1 gene is
      located on chromosome IV, is approximately 6 kb in length, contains 16 exons and
      encodes fibulin-1C and D variants. Comparative analysis of the deduced amino acid
      sequences of nematode and chicken fibulin-1 variants with other known vertebrate
      fibulin-1 polypeptides showed that the number and organization of structural
      modules are identical. The results of this study indicate that the structure of
      the fibulin-1 protein has remained highly conserved over a large period of
      evolution, suggestive of functional conservation.

PMID- 9923657
TI  - Laminin localization in enterocytic basement membrane of rat small bowel grafts.
      A light and electron microscopic study.
AB  - In vitro laminins stimulate numerous biological effects, such as cell migration,
      proliferation, attachment and differentiation. In vitro laminins influence
      immunocompetent cells and in vivo possibly play an important role in graft
      rejection. To establish how laminins could be involved in the regulation of acute
      rejection of small bowel allografts (with and without immunosuppression), we
      investigated laminin distribution in rat small bowel allografts four days after
      transplantation, i.e., before the onset of histological signs of rejection, using
      antibodies against alpha1, beta1, gamma1 chain of laminin-1. In immunosuppressed
      allografts, the ultrastructure of the enterocytic basement membrane appeared
      normal, but no laminin staining was seen in this membrane, although basement
      membranes of intramural blood vessels and muscle cells were normally stained. In
      non-operated immunosuppressed rats, laminin staining was clearly reduced in the
      enterocytic basement membrane, demonstrating that cyclosporin A is able to affect
      this membrane. Since only rats in which laminin is altered survive, this laminin
      alteration in the enterocytic basement membrane presumably plays an important
      role in overcoming the acute rejection.

PMID- 9923658
TI  - A novel and simple immunocapture assay for determination of gelatinase-B (MMP-9)
      activities in biological fluids: saliva from patients with Sjogren's syndrome
      contain increased latent and active gelatinase-B levels.
AB  - Here we describe a new principle for accessing the activity of the different
      members of the human matrix-metalloproteinases (MMPs) by a colorimetric assay.
      Using protein engineering, a modified pro-urokinase was made in which the
      activation sequence, normally recognized by plasmin (ProArgPheLys/IleIleGlyGly),
      was replaced by a sequence that is specifically recognized by MMPs
      (ArgProLeuGly/IleIleGlyGly). The active urokinase resulting from the activation
      of this modified pro-urokinase by MMPs can be measured directly using a
      chromogenic peptide substrate for urokinase. The assay has been made specific for
      MMP-9 using an MMP-9 specific monoclonal antibody. Using this antibody MMP-9 is
      captured from biological fluids or tissue culture media, and MMP-activity of both
      active and latent MMP-9 can be analysed. We determined the gelatinase-B (MMP-9)
      activity present in saliva from patients with Sjogren's syndrome. Using a general
      gelatinase assay with radioactively-labeled gelatinated collagen it was observed
      that gelatinase activity was slightly, though not significantly, increased in
      patients: general gelatinase activity in patients versus healthy controls: 17.0
      +/- 4.9 vs 12.2 +/- 2.5 x 10(4) cpm/ml (p > 0.05, and 44.0 (4.0 vs 36.1 +/- 1.9 x
      10(4) cpm/ml (p > 0.05), for active and latent gelatinase, respectively. However,
      using the immunocapture activity assay (using modified urokinase) specifically
      MMP-9 activity was measured, which was significantly increased in saliva from
      patients compared to healthy controls: MMP-9 (already active): patients 8.9 +/-
      2.5 U/mg, controls 1.0 +/- 0.5 U/mg (p = 0.002); latent plus active MMP-9:
      patients 53.1 +/- 9.8 U/mg, controls 16.5 +/- 2.6 U/mg (p = 0.01). This assay,
      measuring MMP-9 activity using modified pro-urokinase as a substrate can easily
      be adapted for the specific detection of the various members of the MMP-family or
      other difficult to measure proteases, in a format that can be used for high
      throughput screening of compounds or samples.

PMID- 9923659
TI  - Exogenous non-crosslinked collagen enhances granulation tissue formation in
      dermal excision wounds in guinea pigs.
AB  - Based on previous observations indicating a role for collagen peptides in
      eliciting a positive feedback for collagen biosynthesis, this study was initiated
      to elucidate the effect of non-crosslinked collagen on granulation tissue
      formation in dermal excision wounds. The wounds were treated with either non
      crosslinked or crosslinked native collagen, or left untreated as controls.
      Granulation tissue was analyzed for collagen type I mRNA, for levels of
      interstitial collagen and for the number of blood vessels. The results indicated
      significant increases in procollagen type I mRNA, in interstitial collagen, in
      the number of blood vessels and in epithelial advance in the non-crosslinked
      collagen-treated wounds relative to the untreated controls. It is assumed that
      the presence of non-crosslinked collagen in a healing wound enhances both
      procollagen type I biosynthesis and the repair process of dermal wounds, due to
      the more readily released collagen peptides derived from this exogenous collagen
      dressing.

PMID- 9923661
TI  - Does bound water contribute to the stability of collagen?

PMID- 9923660
TI  - Epitope-specific monoclonal antibodies against human C-terminal procollagen
      alpha1(III)-propeptide.
AB  - We have generated monoclonal antibodies against recombinant C-terminal human
      procollagen alpha1(III) propeptide (PIIICP), produced in E. coli in high yields.
      The monoclonal antibodies were screened for epitope specificity using recombinant
      truncated PIIICP. Several antibodies were identified which recognized different
      regions of the PIIICP molecule. The ability of the antibodies to detect PIIICP
      antigens in human cell line lysates and supernatants was demonstrated. As PIIICP
      antigens are a key marker of extracellular matrix metabolism, the monoclonal
      antibodies described here should be of value for clinical and basic research.

PMID- 9923662
TI  - Can physics deliver another biological revolution?

PMID- 9923663
TI  - US biologists propose launch of electronic preprint archive.

PMID- 9923664
TI  - Energy department revises terms of Venter deal after complaints.

PMID- 9923666
TI  - Senator seeks reassurance on NIH budget.

PMID- 9923665
TI  - Gene therapy pushes on, despite doubts.

PMID- 9923667
TI  - Lab guidelines aim to prevent misconduct.

PMID- 9923669
TI  - Neurobiology. Modulation minimizes masking.

PMID- 9923668
TI  - Cell cycle. Checkpoint on the nuclear frontier.

PMID- 9923670
TI  - Signal transduction. An anchor for activation.

PMID- 9923671
TI  - Alan Hodgkin (1914-98)

PMID- 9923672
TI  - Sign language 'heard' in the auditory cortex.

PMID- 9923673
TI  - A single myosin head moves along an actin filament with regular steps of 5.3
      nanometres.
AB  - Actomyosin, a complex of actin filaments and myosin motor proteins, is
      responsible for force generation during muscle contraction. To resolve the
      individual mechanical events of force generation by actomyosin, we have developed
      a new instrument with which we can capture and directly manipulate individual
      myosin subfragment-1 molecules using a scanning probe. Single subfragment-1
      molecules can be visualized by using a fluorescent label. The data that we obtain
      using this technique are consistent with myosin moving along an actin filament
      with single mechanical steps of approximately 5.3 nanometres; groups of two to
      five rapid steps in succession often produce displacements of 11 to 30
      nanometres. This multiple stepping is produced by a single myosin head during
      just one biochemical cycle of ATP hydrolysis.

PMID- 9923674
TI  - Entropic trapping of macromolecules by mesoscopic periodic voids in a polymer
      hydrogel.
AB  - The separation of macromolecules such as polymers and DNA by means of
      electrophoresis, gel permeation chromatography or filtration exploits size
      dependent differences in the time it takes for the molecules to migrate through a
      random porous network. Transport through the gel matrices, which usually consist
      of full swollen crosslinked polymers, depends on the relative size of the
      macromolecule compared with the pore radius. Sufficiently small molecules are
      thought to adopt an approximately spherical conformation when diffusing through
      the gel matrix, whereas larger ones are forced to migrate in a snake-like
      fashion. Molecules of intermediate size, however, can get temporarily trapped in
      the largest pores of the matrix, where the molecule can extend and thus maximize
      its conformational entropy. This 'entropic trapping' is thought to increase the
      dependence of diffusion rate on molecular size. Here we report the direct
      experimental verification of this phenomenon. Bragg diffraction from a hydrogel
      containing a periodic array of monodisperse water voids confirms that polymers of
      different weights partition between the hydrogel matrix and the water voids
      according to the predictions of the entropic trapping theory. Our approach might
      also lead to the design of improved separation media based on entropic trapping.

PMID- 9923675
TI  - A nanomechanical device based on the B-Z transition of DNA.
AB  - The assembly of synthetic, controllable molecular mechanical systems is one of
      the goals of nanotechnology. Protein-based molecular machines, often driven by an
      energy source such as ATP, are abundant in biology. It has been shown previously
      that branched motifs of DNA can provide components for the assembly of nanoscale
      objects, links and arrays. Here we show that such structures can also provide the
      basis for dynamic assemblies: switchable molecular machines. We have constructed
      a supramolecular device consisting of two rigid DNA 'double-crossover' (DX)
      molecules connected by 4.5 double-helical turns. One domain of each DX molecule
      is attached to the connecting helix. To effect switchable motion in this
      assembly, we use the transition between the B and Z forms of DNA. In conditions
      that favour B-DNA, the two unconnected domains of the DX molecules lie on the
      same side of the central helix. In Z-DNA-promoting conditions, however, these
      domains switch to opposite sides of the helix. This relative repositioning is
      detected by means of fluorescence resonance energy transfer spectroscopy, which
      measures the relative proximity of two dye molecules attached to the free ends of
      the DX molecules. The switching event induces atomic displacements of 20-60 A.

PMID- 9923676
TI  - Responses of auditory-cortex neurons to structural features of natural sounds.
AB  - Sound-processing strategies that use the highly non-random structure of natural
      sounds may confer evolutionary advantage to many species. Auditory processing of
      natural sounds has been studied almost exclusively in the context of species
      specific vocalizations, although these form only a small part of the acoustic
      biotope. To study the relationships between properties of natural soundscapes and
      neuronal processing mechanisms in the auditory system, we analysed sound from a
      range of different environments. Here we show that for many non-animal sounds and
      background mixtures of animal sounds, energy in different frequency bands is
      coherently modulated. Co-modulation of different frequency bands in background
      noise facilitates the detection of tones in noise by humans, a phenomenon known
      as co-modulation masking release (CMR). We show that co-modulation also improves
      the ability of auditory-cortex neurons to detect tones in noise, and we propose
      that this property of auditory neurons may underlie behavioural CMR. This
      correspondence may represent an adaptation of the auditory system for the use of
      an attribute of natural sounds to facilitate real-world processing tasks.

PMID- 9923677
TI  - Kainate receptors mediate synaptic transmission between cones and 'Off' bipolar
      cells in a mammalian retina.
AB  - Light produces a graded hyperpolarization in retinal photoreceptors that
      decreases their release of synaptic neurotransmitter. Cone photoreceptors use
      glutamate as a neurotransmitter with which to communicate with two types of
      bipolar cell. Activation of metabotropic glutamate receptors in 'On' bipolar
      cells initiates a second-messenger cascade that can amplify small synaptic inputs
      from cones. In contrast, it is not known how the ionotropic glutamate receptors
      that are activated in 'Off' bipolar cells are optimized for transmitting small,
      graded signals. Here we show, by recording from a cone and a synaptically
      connected 'Off' bipolar cell in slices of retina from the ground squirrel, that
      transmission is mediated by glutamate receptors of the kainate-preferring
      subtype. In the dark, a cone releases sufficient neurotransmitter to desensitize
      most postsynaptic kainate receptors. The small postsynaptic current that persists
      (<5% of maximum) is quickly modulated by changes in presynaptic voltage. Since
      recovery from desensitization is slow (the decay time constant is roughly 500
      milliseconds), little recovery can occur during the brief (roughly 100
      millisecond) hyperpolarization that is produced in cones by a flash of light. By
      limiting the postsynaptic current, receptor desensitization prevents saturation
      of the 'Off' bipolar cell's voltage response and allows the synapse to operate
      over the cone's entire physiological voltage range.

PMID- 9923678
TI  - Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord.
AB  - Glutamate, the major excitatory neurotransmitter in the central nervous system,
      activates three different receptors that directly gate ion channels, namely
      receptors for AMPA (alpha-amino-3-hydroxy-5-methyl isoxozole propionic acid),
      NMDA (N-methyl-D-aspartate), and kainate, a structural analogue of glutamate. The
      contribution of AMPA and NMDA receptors to synaptic transmission and plasticity
      is well established. Recent work on the physiological function of kainate
      receptors has focused on the hippocampus, where repetitive activation of the
      mossy-fibre pathway generates a slow, kainate-receptor-mediated excitatory
      postsynaptic current (EPSC). Here we show that high-intensity single-shock
      stimulation (of duration 200 microseconds) of primary afferent sensory fibres
      produces a fast, kainate-receptor-mediated EPSC in the superficial dorsal horn of
      the spinal cord. Activation of low-threshold afferent fibres generates typical
      AMPA-receptor-mediated EPSCs only, indicating that kainate receptors may be
      restricted to synapses formed by high-threshold nociceptive (pain-sensing) and
      thermoreceptive primary afferent fibres. Consistent with this possibility,
      kainate-receptor-mediated EPSCs are blocked by the analgesic mu-opiate-receptor
      agonist Damgo and spinal blockade of both kainate and AMPA receptors produces
      antinociception. Thus, spinal kainate receptors contribute to transmission of
      somatosensory inputs from the periphery to the brain.

PMID- 9923679
TI  - The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and
      senescence through the ink4a locus.
AB  - The bmi-1 gene was first isolated as an oncogene that cooperates with c-myc in
      the generation of mouse lymphomas. We subsequently identified Bmi-1 as a
      transcriptional repressor belonging to the mouse Polycomb group. The Polycomb
      group comprises an important, conserved set of proteins that are required to
      maintain stable repression of specific target genes, such as homeobox-cluster
      genes, during development. In mice, the absence of bmi-1 expression results in
      neurological defects and severe proliferative defects in lymphoid cells, whereas
      bmi-1 overexpression induces lymphomas. Here we show that bmi-1-deficient primary
      mouse embryonic fibroblasts are impaired in progression into the S phase of the
      cell cycle and undergo premature senescence. In these fibroblasts and in bmi-1
      deficient lymphocytes, the expression of the tumour suppressors p16 and p19Arf,
      which are encoded by ink4a, is raised markedly. Conversely, overexpression of bmi
      1 allows fibroblast immortalization, downregulates expression of p16 and p19Arf
      and, in combination with H-ras, leads to neoplastic transformation. Removal of
      ink4a dramatically reduces the lymphoid and neurological defects seen in bmi-1
      deficient mice, indicating that ink4a is a critical in vivo target for Bmi-1. Our
      results connect transcriptional repression by Polycomb-group proteins with cell
      cycle control and senescence.

PMID- 9923680
TI  - Robustness in bacterial chemotaxis.
AB  - Networks of interacting proteins orchestrate the responses of living cells to a
      variety of external stimuli, but how sensitive is the functioning of these
      protein networks to variations in their biochemical parameters? One possibility
      is that to achieve appropriate function, the reaction rate constants and enzyme
      concentrations need to be adjusted in a precise manner, and any deviation from
      these 'fine-tuned' values ruins the network's performance. An alternative
      possibility is that key properties of biochemical networks are robust; that is,
      they are insensitive to the precise values of the biochemical parameters. Here we
      address this issue in experiments using chemotaxis of Escherichia coli, one of
      the best-characterized sensory systems. We focus on how response and adaptation
      to attractant signals vary with systematic changes in the intracellular
      concentration of the components of the chemotaxis network. We find that some
      properties, such as steady-state behaviour and adaptation time, show strong
      variations in response to varying protein concentrations. In contrast, the
      precision of adaptation is robust and does not vary with the protein
      concentrations. This is consistent with a recently proposed molecular mechanism
      for exact adaptation, where robustness is a direct consequence of the network's
      architecture.

PMID- 9923681
TI  - Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein.
AB  - DNA damage activates a cell-cycle checkpoint that prevents mitosis while DNA
      repair is under way. The protein Chk1 enforces this checkpoint by phosphorylating
      the mitotic inducer Cdc25. Phosphorylation of Cdc25 by Chk1 creates a binding
      site in Cdc25 for 14-3-3 proteins, but it is not known how 14-3-3 proteins
      regulate Cdc25. Rad24 is a 14-3-3 protein that is important in the DNA-damage
      checkpoint in fission yeast. Here we show that Rad24 controls the intracellular
      distribution of Cdc25. Elimination of Rad24 causes nuclear accumulation of Cdc25.
      Activation of the DNA-damage checkpoint causes the net nuclear export of Cdc25 by
      a process that requires Chk1, Rad24 and nuclear-export machinery. Mutation of a
      putative nuclear-export signal in Rad24 impairs the nuclear exclusion of Rad24,
      the damage-induced nuclear export of Cdc25 and the damage checkpoint. Thus, Rad24
      appears to function as an attachable nuclear-export signal that enhances the
      nuclear export of Cdc25 in response to DNA damage.

PMID- 9923682
TI  - Genomic-sequence comparison of two unrelated isolates of the human gastric
      pathogen Helicobacter pylori.
AB  - Helicobacter pylori, one of the most common bacterial pathogens of humans,
      colonizes the gastric mucosa, where it appears to persist throughout the host's
      life unless the patient is treated. Colonization induces chronic gastric
      inflammation which can progress to a variety of diseases, ranging in severity
      from superficial gastritis and peptic ulcer to gastric cancer and mucosal
      associated lymphoma. Strain-specific genetic diversity has been proposed to be
      involved in the organism's ability to cause different diseases or even be
      beneficial to the infected host and to participate in the lifelong chronicity of
      infection. Here we compare the complete genomic sequences of two unrelated H.
      pylori isolates. This is, to our knowledge, the first such genomic comparison. H.
      pylori was believed to exhibit a large degree of genomic and allelic diversity,
      but we find that the overall genomic organization, gene order and predicted
      proteomes (sets of proteins encoded by the genomes) of the two strains are quite
      similar. Between 6 to 7% of the genes are specific to each strain, with almost
      half of these genes being clustered in a single hypervariable region.

PMID- 9923683
TI  - Protein dynamics from NMR.
AB  - The past several years have seen the development of a significant number of new
      multidimensional NMR methods for the study of molecular dynamics spanning a wide
      range of time scales. Applications involving a large number of different
      biological systems have emerged and correlations with function have been
      established. Unique insights are obtained that are not available from structure
      alone, indicating the importance of dynamics studies for understanding function.

PMID- 9923684
TI  - Protein chemical shift analysis: a practical guide.
AB  - Proper protein chemical shift analysis requires careful experimental measurements
      and the implementation of standardized referencing procedures. In this article we
      outline the steps necessary to ensure proper chemical shift referencing and the
      selection criteria for choosing appropriate "random coil" amino acid chemical
      shift values for predicting, comparing, and assigning 1H, 13C, and 15N resonances
      in proteins. By making use of these standardized conditions we demonstrate how
      several recently developed methods, namely homologous assignment techniques and
      empirical chemical shift contour maps (or hypersurfaces), can significantly
      improve the accuracy of chemical shift prediction for 1H, 13C, and 15N nuclei. In
      addition to illustrating the potential utility of chemical shift prediction, we
      also outline procedures for identifying secondary structure elements through
      heteronuclear chemical shift analysis and further demonstrate how empirical shift
      contour maps can actually be used to refine, and more importantly generate,
      reasonably good three-dimensional protein structures.

PMID- 9923686
TI  - Blurring the distinction between slow and intermediate chemical exchange.
AB  - NMR is a vital tool for measuring the dynamics of biological macromolecules in
      solution. The chemical exchange observed is often divided into slow or
      intermediate exchange. Slow exchange affects principally the z magnetizations of
      the system and is observed in modified spin-lattice relaxation experiments.
      Intermediate exchange gives rise to broadening and coalescence in the spectrum
      itself. This broadened spectrum is often considered as a whole, but we have shown
      that it is better to regard it as a sum of transitions, with a generalized
      picture of the transition probability. In this paper, we give explicit
      expressions for the lineshape for two sites and review some of the recent
      applications of chemical exchange in biochemical NMR.

PMID- 9923685
TI  - The solution conformations of amino acids from molecular dynamics simulations of
      Gly-X-Gly peptides: comparison with NMR parameters.
AB  - The conformations that amino acids can adopt in the random coil state are of
      fundamental interest in the context of protein folding research and studies of
      protein-peptide interactions. To date, no detailed quantitative data from
      experimental studies have been reported; only nuclear magnetic resonance
      parameters such as chemical shifts and J coupling constants have been reported.
      These experimental nuclear magnetic resonance data represent averages over
      multiple conformations, and hence they do not provide unique structural
      information. I have performed relatively long (2.5 ns) molecular dynamics
      simulations of Gly-X-Gly tripeptides, surrounded by explicit water molecules,
      where X represents eight different amino acids with long side chains. From the
      trajectories one can calculate time averaged backbone chemical shifts and 3J(NH
      alpha) coupling constants and compare these with experimental data. These
      calculated quantities are quite close to the experimental values for most amino
      acids, suggesting that these simulations are a good model for the random coil
      state of the tripeptides. On the basis of my simulations I predict 3J(alphabeta)
      coupling constants and present dihedral distributions for the phi, psi, as well
      as chi1 and chi2 angles. Finally, I present correlation plots for these dihedral
      angles.

PMID- 9923687
TI  - NMR for the design of functional mimetics of protein-protein interactions: one
      key is in the building of bridges.
AB  - Using the design of bivalent and bridge-binding inhibitors of thrombin as an
      example, we review an NMR-based experimental approach for the design of
      functional mimetics of protein-protein interactions. The strategy includes: (i)
      identification of binding residues in peptide ligands by differential resonance
      perturbation, (ii) determination of protein-bound structures of peptide ligands
      by use of transferred NOEs, (iii) minimization of larger protein and peptide
      ligands on the basis of NMR structural information, and (iv) linkage of two
      weakly binding mimetics to produce an inhibitor with enhanced affinity and
      specificity. This approach can be especially effective for the design of potent
      and selective functional mimetics of protein-protein interactions because it is
      less likely that the surfaces of two related proteins or enzymes share two
      identical binding sites or regions.

PMID- 9923689
TI  - Theoretical calculations of acid-dissociation constants of proteins.
AB  - The purpose of this review is to introduce several computational procedures for
      the determination of acid-dissociation constants (pKa) of titratable groups in
      proteins. Several concepts, such as continuum electrostatics and the exact
      meaning of intrinsic and apparent pKas, will be explained in some detail. Each of
      the methods will be judged on its merits, and some comparisons between the
      methods will be presented. While the emphasis of this review will be on
      theoretical formulations, the experimental determination by means of nuclear
      magnetic resonance will be briefly explained. The determination of individual pKa
      values by nuclear magnetic resonance in combination with computationally
      determined pKas can provide unique information about the pH-dependent properties
      of proteins and their complexes with peptides, DNA, and ligands.

PMID- 9923688
TI  - An NMR study of ligand binding by maltodextrin binding protein.
AB  - Proton NMR spectra of maltodextrin binding protein from Escherichia coli were
      used to monitor conformational changes that accompany ligand binding. Chemical
      shift changes associated with the binding of different maltodextrins to
      maltodextrin binding protein were studied using one-dimensional difference
      spectra. Line-shape analysis of an isolated upfield methyl resonance was used to
      measure the kinetics of maltose binding at several temperatures. Maltose and
      linear maltodextrins caused similar changes to the upfield protein spectrum with
      no detectable differences between alpha and beta sugar anomers. Binding of a
      cyclic ligand, beta-cyclodextrin, caused smaller chemical shift changes than
      binding of linear maltodextrins. Two maltodextrin derivatives were also studied.
      Both maltohexaitol and maltohexanoic acid gave one-dimensional difference spectra
      that were intermediate between those of linear maltodextrins and beta
      cyclodextrin. The methyl resonances at -1 and -0.35 ppm were assigned to leucine
      160 on the basis of homonuclear COSY and TOCSY experiments and theoretical
      chemical shift calculations using the X-ray crystal structure of maltodextrin
      binding protein.

PMID- 9923690
TI  - Quadrupolar metal ion NMR studies of metalloproteins.
AB  - We present a summary of the quadrupolar metal ion NMR studies of metalloproteins
      conducted in our laboratory in recent years. The approaches we employ can be
      subdivided into two categories: (i) the use of low-frequency metal nuclei to
      probe metal ion binding sites in small proteins, exemplified by 43Ca NMR studies
      of alpha-lactalbumins and calcium-binding lysozymes, and (ii) the novel detection
      of the central transition of half-integer quadrupolar nuclei of moderate
      frequency bound to large metalloproteins, typified by 27Al, 45Sc, 69,71Ga, and
      51V NMR studies of the transferrins. We highlight the chemical information
      regarding the nature of metal ion binding sites that can be obtained from this
      technique and emphasize the salient parameters that an investigator must consider
      to successfully apply quadrupolar NMR to the study of biological macromolecules.

PMID- 9923691
TI  - NMR spectroscopic studies of I = 1/2 metal ions in biological systems.
AB  - This article reviews the use of nuclear magnetic resonance methods of spin 1/2
      metal nuclei to probe the metal binding site(s) in a variety of metalloproteins.
      The majority of the studies have involved native Zn(II) and Ca(II)
      metalloproteins where there has been isostructural substitution of these metal
      ions with the I = 1/2 (111/113)Cd(II) ion. Also included are recent studies that
      have utilized the 109Ag(I) ion to probe Cu(I) sites in yeast metallothionein and
      199Hg(II) as a probe of the metal binding sites in mercury resistance proteins.
      Pertinent aspects for the optimal execution of these experiments along with the
      procedures for the metal substitution reactions are discussed together with the
      presentation of a 113Cd chemical shift correlation map with ligand type and
      coordination number. Specific examples of protein systems studied using the
      (111/113)Cd and 109Ag nuclei include the metallothionein superfamily of Zn(II)-
      and Cu(I)-binding proteins from mammalian, invertebrate, and yeast systems. In
      addition to the structural features revealed by these metal ion nuclear magnetic
      resonance studies, important new information is frequently provided about the
      dynamics at the active-site metal ion. In an effort for completeness, other less
      frequently used spin 1/2 metal nuclei are mentioned.

PMID- 9923692
TI  - Structure-function relationships of antimicrobial peptides.
AB  - Antimicrobial peptides are ubiquitously produced throughout nature. Many of these
      relatively short peptides (6-50 residues) are lethal towards bacteria and fungi,
      yet they display minimal toxicity towards mammalian cells. All of the peptides
      are highly cationic and hydrophobic. It is widely believed that they act through
      nonspecific binding to biological membranes, even though the exact nature of
      these interactions is presently unclear. High-resolution nuclear magnetic
      resonance (NMR) has contributed greatly to knowledge in this field, providing
      insight about peptide structure in aqueous solution, in organic cosolvents, and
      in micellar systems. Solid-state NMR can provide additional information about
      peptide-membrane binding. Here we review our current knowledge about the
      structure of antimicrobial peptides. We also discuss studies pertaining to the
      mechanism of action. Despite the different three-dimensional structural motifs of
      the various classes, they all have similar amphiphilic surfaces that are well
      suited for membrane binding. Many antimicrobial peptides bind in a membrane
      parallel orientation, interacting only with one face of the bilayer. This may be
      sufficient for antimicrobial action. At higher concentrations, peptides and
      phospholipids translocate to form multimeric transmembrane channels that seem to
      contribute to the peptide's hemolytic activity. An understanding of the key
      features of the secondary and tertiary structures of the antimicrobial peptides
      and their effects on bactericidal and hemolytic activity can aid the rational
      design of improved analogs for clinical use.

PMID- 9923693
TI  - NMR studies of the antimicrobial salivary peptides histatin 3 and histatin 5 in
      aqueous and nonaqueous solutions.
AB  - Conformational studies of the salivary peptides histatin 3 (H3) and histatin 5
      (H5) were performed by NMR and circular dichroism (CD) in aqueous and nonaqueous
      solutions. Histatin 5 has no defined structure in H2O but adopts a more helical
      conformation in dimethyl sulfoxide and aqueous trifluoroethanol. This is in
      agreement with the CD analysis, which shows no secondary structure in H2O but
      increasing helical content in the presence of trifluoroethanol. CD analysis shows
      that H3 has less propensity to form a helical structure than H5 in similar
      conditions. The NMR analysis of H3 in H2O at pH 7.4 reveals that its
      conformational mobility is less than that of H5 as indicated by the observation
      of backbone cross peaks alphaN (i, i + 1) and NN (i, i + 1) and the slow
      exchanging amide protons in the C-terminus. However, H3 remains essentially
      unordered as suggested by the lack of longer range nuclear Overhauser effects
      (NOEs) in the NOESY spectrum. H3 becomes much more ordered in a mixture of 50:50
      H2O-dimethyl sulfoxide as indicated by the numerous NOEs, including several side
      chain to side chain and side chain to backbone connectivities. Our data suggest
      that in these conditions H3 contains a turn in the region of K13 to K17 and
      possibly a 3(10) helix at the C-terminus. This study demonstrates that H3 and H5
      are both conformationally mobile and that each adopt different types of
      conformations in aqueous and nonaqueous solutions.

PMID- 9923694
TI  - NMR and CD conformational studies of bradykinin and its agonists and antagonists:
      application to receptor binding.
AB  - Most physiological processes are regulated by peptides that perform their
      functions by interacting with specific receptors on cells. Specific conformations
      of the peptides are required for correct interactions to take place, and a
      knowledge of the biologically important conformation is vital for the
      understanding of biological function. Over the last few years extensive studies
      using nuclear magnetic resonance and circular dichroism have been carried out on
      bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) and its antagonists
      with the objective of developing new drugs to combat severe pathologies
      associated with its production. In the present review, these techniques for the
      determination of peptide conformation are reviewed and applied to the study of
      bradykinin and its antagonists. Modeling of these conformational data in the
      presence of the B2 receptor or an antibody allows the biologically active
      conformations to be deduced and these are presented in this review.

PMID- 9923695
TI  - Sequence-specific 1H NMR resonance assignments and secondary structure of human
      apolipoprotein C-I in the presence of sodium dodecyl sulfate.
AB  - Apolipoprotein (apo) C-I is a 57-residue exchangeable plasma protein distributed
      mainly in high and very low density lipoprotein. In this report we present the
      nuclear magnetic resonance spectra of native apoC-I and synthetic apoC-I,
      containing selected 15N-labelled amino acids, in the presence of sodium dodecyl
      sulfate. The proton resonances of apoC-I are assigned and the secondary structure
      is estimated from the difference of measured alpha-proton chemical shifts to
      random coil values and the observed NOE interactions. According to these data
      apoC-I forms two helices, Val-4-Lys-30 and Leu-34-Lys-52, linked by an
      unstructured region Gln-31-Glu-33. The N-terminal segments of each helix, Val-4
      Gly-15 and Leu-34-Met-38, appear to be more flexible than the helical core
      regions Asn-16-Lys-30 and Arg-39-Lys-52.

PMID- 9923696
TI  - NMR evidence for a conformational adaptation of apolipophorin III upon lipid
      association.
AB  - A characteristic property of amphipathic exchangeable apolipoproteins is an
      ability to exist alternately in lipid-free and lipid-bound states. In the present
      study, we have used 1H-15N-heteronuclear single quantum correlation spectroscopy
      to probe structural changes of apolipophorin III upon lipid association, by
      monitoring alterations of the chemical shifts of specific amino acids as a
      function of lipid titration. 15N-valine-, 15N-leucine-, 15N-lysine-, and 15N
      glycine-labeled apolipophorin III were used in titration experiments with the
      micelle-forming lipid dodecylphosphocholine. In the absence of lipid, valine and
      leucine residues are located in the hydrophobic interior of the apolipophorin III
      helix bundle and their resonances resist chemical shift changes below the
      critical micelle concentration of dodecylphosphocholine. At the critical micelle
      concentration, however, dramatic and abrupt chemical shift changes occur,
      apparently coincident with formation of a protein-lipid micelle complex, as
      judged by significant line-width broadening of the crosspeaks. By contrast,
      apolipophorin III lysine and glycine residues are located on the hydrophilic
      surfaces of amphipathic alpha-helices or in loop regions, exposed to solvent.
      Their crosspeaks display either a chemical shift change similar to that seen for
      hydrophobic residues or a more gradual chemical shift change, beginning at very
      low dodecylphosphocholine concentrations. These results indicate that an
      interaction occurs between specific solvent-exposed lysine residues and
      dodecylphosphocholine below the critical micelle concentration of this lipid,
      whereas valine and leucine residues are not accessible to monomeric
      dodecylphosphocholine. At the critical micelle concentration, however, the
      availability of a newly formed lipid surface induces apolipophorin III binding,
      concomitant with conformational opening of the helix bundle, exposing its
      hydrophobic surfaces for binding to the dodecylphosphocholine micellar surface.
      Subsequently, hydrophobic residues undergo characteristic spectral changes.
      Subtle differences in behavior of specific hydrophobic residues, in terms of
      their response to dodecylphosphocholine titration and relative locations in the
      helix-bundle conformation, suggest that one end of the molecule may initiate
      contact with the lipid surface, followed by helix bundle opening.

PMID- 9923697
TI  - NMR structural studies on antifreeze proteins.
AB  - Antifreeze proteins (AFPs) are a structurally diverse class of proteins that bind
      to ice and inhibit its growth in a noncolligative manner. This adsorption
      inhibition mechanism operating at the ice surface results in a lowering of the
      (nonequilibrium) freezing point below the melting point. A lowering of
      approximately 1 degree C, which is sufficient to prevent fish from freezing in
      ice-laden seawater, requires millimolar AFP levels in the blood. The solubility
      of AFPs at these millimolar concentrations and the small size of the AFPs
      (typically 3-15 kDa) make them ideal subjects for NMR analysis. Although fish
      AFPs are naturally abundant, seasonal expression, restricted access to polar
      fishes, and difficulties in separating numerous similar isoforms have made
      protein expression the method of choice for producing AFPs for structural
      studies. Expression of recombinant AFPs has also facilitated NMR analysis by
      permitting isotopic labeling with 15N and 13C and has permitted mutations to be
      made to help with the interpretation of NMR data. NMR analysis has recently
      solved two AFP structures and provided valuable information about the disposition
      of ice-binding side chains in a third. The potential exists to solve other AFP
      structures, including the newly described insect AFPs, and to use solid-state NMR
      techniques to address fundamental questions about the nature of the interaction
      between AFPs and ice.

PMID- 9923698
TI  - Two-dimensional 1H and 15N NMR titration studies of hisactophilin.
AB  - We have used two-dimensional 1H-15N heteronuclear single quantum correlation
      spectroscopy to measure the pH dependence of backbone amide group chemical shifts
      in the actin binding protein hisactophilin over the pH range 5.7-11.1. Most of
      the resonances can be analyzed using a simple equation involving a single
      apparent ionization constant, pK(app). The majority of resonances in the protein
      titrate with pK(app) values of 5.6-7.4. The results can be rationalized in terms
      of titration of many histidine residues in hisactophilin. The titration data
      provide direct experimental support for the proposed models of the atomic basis
      of actin and membrane binding by hisactophilin.

PMID- 9923700
TI  - Molecular mechanisms of calmodulin's functional versatility.
AB  - Calmodulin (CaM) is a primary Ca2+-binding protein found in all eukaryotic cells.
      It couples the intracellular Ca2+ signal to many essential cellular events by
      binding and regulating the activities of more than 40 different proteins and
      enzymes in a Ca2+-dependent manner. CaM contains two structurally similar domains
      connected by a flexible central linker. Each domain of the protein binds two Ca2+
      ions with positive cooperativity. The binding of Ca2+ transforms the protein into
      its active form through a reorientation of the existing helices of the protein.
      The two helices in each helix-loop-helix Ca2+-binding motif are almost
      antiparallel in Ca2+-free CaM. The binding of Ca2+ induces concerted helical pair
      movements and changes the two helices in each Ca2+ binding motif to a nearly
      perpendicular orientation. These concerted helix pair movements are accompanied
      by dramatic changes on the molecular surface of the protein. Rather than
      exhibiting a flat, hydrophilic molecular surface as seen in Ca2+-free CaM, the
      Ca2+-saturated form of the protein contains a Met-rich, cavity-containing
      hydrophobic surface in each domain. These hydrophobic surfaces are largely
      responsible for the binding of CaM to its targets. The unique flexibility and
      high polarizability of the Met residues located at the entrance of each
      hydrophobic pocket together with other hydrophobic amino acid residues create
      adjustable, sticky interaction surface areas that can accommodate CaM's targets,
      which have various sizes and shapes. Therefore, CaM is able to bind to a large
      array of targets without obvious sequence homology. Upon binding to its target
      peptides, the unwinding of the central linker allows the two domains of the
      protein to engulf the hydrophobic face of target peptides of differing lengths.
      The binding of Ca2+ reduces the backbone flexibility of CaM. Formation of
      complexes with its target peptides further decreases the backbone motion of CaM.

PMID- 9923699
TI  - The NMR angle on troponin C.
AB  - The calcium-induced structural changes in the skeletal muscle regulatory protein
      troponin C involve a transition from a closed to an open structure with the
      concomitant exposure of a large hydrophobic interaction site for target proteins.
      NMR solution structural studies have served to define this conformational change
      and elucidate the mechanism of the linkage between calcium binding and the
      induced structural changes. These structural movements are described in terms of
      interhelical angles in these largely helical proteins. Oddly, the most recent
      structure of the cardiac system challenges the central paradigm because the
      calcium-bound structures are not open. The kinetics, energetics, and dynamics of
      these proteins have also been investigated using NMR.

PMID- 9923701
TI  - A change-in-hand mechanism for S100 signalling.
AB  - S100 proteins are a group of small dimeric calcium-binding proteins making up a
      large subclass of the EF-hand family of calcium-binding proteins. Members of this
      family of proteins have been proposed to act as intracellular calcium modulatory
      proteins in a fashion analogous to that of the EF-hand sensor proteins troponin-C
      and calmodulin. Recently, NMR spectroscopy has provided the three-dimensional
      structures of the S100 family members S100A6 and S100B in both the apo- and
      calcium-bound forms. These structures have allowed for the identification of a
      novel calcium-induced conformational change termed the change-in-hand mechanism.
      Helix III of the C-terminal calcium-binding loop changes its helix-helix
      interactions (or handness) with the remainder of the molecule primarily owing to
      the reorientation of the backbone in an effort to coordinate the calcium ion.
      This reorientation of helix III exposes several residues in the C-terminus and
      linker regions of S100B resulting in the formation of a hydrophobic patch
      surrounded be a number of acidic residues. This site is the proposed region for
      protein-protein recognition.

PMID- 9923702
TI  - Effect of peptide binding on amide proton exchange rates in the PDZ2 domain from
      human phosphatase hPTP1E.
AB  - Amide hydrogen-deuterium exchange rates were measured in the PDZ2 domain from
      human phosphatase hPTPIE by 1H-15N heteronuclear NMR spectroscopy. Protection
      factors were calculated for the slowly exchanging hydrogens in both the free PDZ2
      domain and its complex with an octapeptide peptide, R-N-E-I-Q-S-L-V, derived from
      the C-terminus of the Fas receptor. Aside from a short alpha-helical region
      alpha1 (amino acids A-45 to D-49), the pattern of highly protected amides
      correlated well with the presence of hydrogen bonds in elements of the secondary
      structure. Hydrogen-bonded amides showed relatively fast exchange rates with half
      lives of less than 9 h at pD 7.6 and 8 degrees C. Protection factors, calculated
      as the ratio of theoretical (denatured) and observed exchange rates, showed less
      dispersion in maximal values than did the actual exchange rates. This behavior
      and the large pH dependence of the exchange rates suggest that amide exchange is
      close to the EX2 limit. In this limit, exchange of the most protected amides
      occurs through a global unfolding mechanism. The free energy of the unfolding
      calculated from the largest protection factors is 4.8 +/- 0.4 kcal/mol (1 cal =
      4.184 J). This deltaG(o) closely matches the value measured by experiments with
      guanidine hydrochloride and fluorescence emission spectroscopy. Peptide binding
      to PDZ2 resulted in mostly global effects and stabilized the folded domain by 1.4
      kcal/mol.

PMID- 9923703
TI  - NMR studies of tandem WW domains of Nedd4 in complex with a PY motif-containing
      region of the epithelial sodium channel.
AB  - Nedd4 (neuronal precursor cell-expressed developmentally down-regulated 4) is a
      ubiquitin-protein ligase containing multiple WW domains. We have previously
      demonstrated the association between the WW domains of Nedd4 and PPxY (PY) motifs
      of the epithelial sodium channel (ENaC). In this paper, we report the assignment
      of backbone 1H alpha, 1HN, 15N, 13C', 13C alpha, and aliphatic 13C resonances of
      a fragment of rat Nedd4 (rNedd4) containing the two C-terminal WW domains,
      WW(II+III), complexed to a PY motif-containing peptide derived from the beta
      subunit of rat ENaC, the betaP2 peptide. The secondary structures of these two WW
      domains, determined from chemical shifts of 13C alpha and 13C beta resonances,
      are virtually identical to those of the WW domains of the Yes-associated protein
      YAP65 and the peptidyl-prolyl isomerase Pin1. Triple resonance experiments that
      detect the 1H alpha chemical shift were necessary to complete the chemical shift
      assignment, owing to the large number of proline residues in this fragment of
      rNedd4. A new experiment, which correlates sequential residues via their 15N
      nuclei and also detects 1H alpha chemical shifts, is introduced and its utility
      for the chemical shift assignment of sequential proline residues is discussed.
      Data collected on the WW(II+III)-betaP2 complex indicate that these WW domains
      have different affinities for the betaP2 peptide.

PMID- 9923704
TI  - RING fingers and B-boxes: zinc-binding protein-protein interaction domains.
AB  - The cysteine-rich zinc-binding motifs known as the RING and B-box are found in
      several unrelated proteins. Structural, biochemical, and biological studies of
      these motifs reveal that they mediate protein-protein interactions. Several RING
      containing proteins are oncoproteins and recent data indicate that proapoptotic
      activities can be mediated through the RING. 1H NMR methods were used to
      determine the structures of RINGs and a B-box domain and to monitor the
      conformational changes these motifs undergo upon zinc ligation. This review
      discusses in detail the structural features of the RING and B-box domains.
      Further, possible structure function relationships for these motifs particularly
      in their role as protein interaction domains are discussed.

PMID- 9923705
TI  - The structure and function of HPr.
AB  - Histidine-containing phosphocarrier protein, HPr, was one of the early protein
      tertiary structures determined by two-dimensional 1H-NMR. Tertiary structures for
      HPrs from Escherichia coli, Bacillus subtilis, and Staphylococcus aureus have
      been obtained by 1H NMR and the overall folding pattern of HPr is highly
      conserved, a betaalpha betabeta alphabeta alpha arrangement of three alpha
      helices overlaying a four-stranded beta-sheet. High-resolution structures for
      HPrs from E. coli and B. subtilis have been obtained using 15N- and 13C-labeled
      proteins. The first application of NMR to the understanding of the structure and
      function of HPr was to describe the phosphohistidine isomer, Ndelta1-P-histidine
      in S. aureus phospho-HPr, and the unusual pKas of the His-15 side chain. The pKa
      values for the His-15 imidazole from more recent studies are 5.4 for HPr and 7.8
      for phospho-HPr from E. coli, for example. A consensus description of the active
      site is proposed for HPr and phospho-HPr. In HPr, His-15 has a defined
      conformation and N-caps helix A, and is thus affected by the helix dipole. His-15
      undergoes a small conformational change upon phosphorylation, a movement to allow
      the phosphoryl group to be positioned such that it forms hydrogen bonds with the
      main chain amide nitrogens of residue 16 (not conserved) and Arg-17. Interactions
      between residue 12 side chain (not conserved: asparagine, serine, and threonine)
      and His-15, and between the Arg-17 guanidinium group and the phosphoryl group,
      are either weak or transitory.

PMID- 9923706
TI  - New perceptions of transcription factor properties from NMR.
AB  - The complementarity of NMR and X-ray crystallography for biomacromolecular
      studies has been particularly evident in analysis of transcription factor
      structures and interactions. While X-ray crystallography can be used to tackle
      relatively complicated structural problems including multicomponent (three and
      higher) complexes, NMR studies have provided new insights into the nature of
      protein-DNA and protein-protein interactions that would be difficult to obtain by
      other biophysical methods. We describe herein some of the novel and important
      information recently derived from NMR studies of transcription factors.

PMID- 9923707
TI  - Assigning the NMR spectra of aromatic amino acids in proteins: analysis of two
      Ets pointed domains.
AB  - The measurement of interproton nuclear Overhauser enhancements (NOEs) and
      dihedral angle restraints of aromatic amino acids is a critical step towards
      determining the structure of a protein. The complete assignment of the resonances
      from aromatic rings and the subsequent resolution and identification of their
      associated NOEs, however, can be a difficult task. Shown here is a strategy for
      assigning the 1H, 13C, and 15N signals from the aromatic side chains of
      histidine, tryptophan, tyrosine, and phenylalanine using a suite of homo- and
      hetero-nuclear scalar and NOE correlation experiments, as well as selective
      deuterium isotope labelling. In addition, a comparison of NOE information
      obtained from homonuclear NOE spectroscopy (NOESY) and 13C-edited NOESY
      heteronuclear single quantum correlation experiments indicates that high
      resolution homonuclear two-dimensional NOESY spectra of selectively deuterated
      proteins are invaluable for obtaining distance restraints to the aromatic
      residues.

PMID- 9923708
TI  - NMR spectroscopic and enzymatic studies of DNA hairpins containing mismatches in
      the EcoRI recognition site.
AB  - We have correlated the structural perturbations caused by DNA mismatches with the
      enzymatic data of the interaction of the restriction endonuclease EcoRI with DNA.
      Oligonucleotides d(CGAGAATTCTCA5GAXAATTCT) (X = G, A, T) and
      d(CGCGAATTYGCGT4CGCXAATTCGCG) (Y = C, X = G, T and Y = A, X = T) containing
      single mismatches within the EcoRI recognition site were characterized by NMR
      spectroscopy and by their EcoRI substrate properties. UV melting and gel
      electrophoresis studies confirm that the oligonucleotides form hairpin
      structures. The presence of either a CT or a CA mismatch results in markedly
      lower Tm and van't Hoff enthalpies compared with the fully base paired control.
      NMR imino proton spectra of these hairpins demonstrate that the perturbation
      caused by the two mispairs or a noncanonical AT pair is localized and limited to
      one or two base pairs on either side of the perturbation. The DNA hairpin
      structures containing single mismatches, and to a lesser extent also sequences
      with a single noncanonical base pair, are substrates for the restriction
      endonuclease. In addition to the strand scission at the nonperturbed GpA
      phosphodiester bond some cleavage is observed at the mismatched position. The
      interactions of the CA and CT mismatched hairpin with the enzyme are
      characterized by binding constants that are only 33 and 57 times lower,
      respectively, than that for the canonical sequence, corresponding to 8-10 kJ x
      mol(-1) less favorable free binding energy. This, taken together with the NMR
      data, indicates that the CA and CT mismatches have only small effects on the
      EcoRI recognition of the DNA substrate. We conclude that two out of the three
      hydrogen bonds that characterize the interaction of EcoRI with the CG base pair
      in the canonical sequence can still be formed for either the CT or CA mismatched
      recognition site.

PMID- 9923709
TI  - NMR studies of DNA duplexes containing alpha-anomeric nucleotides and polarity
      reversals.
AB  - We present a summary of our research to date on a family of self-complementary
      DNA decamers containing single alpha-anomeric nucleotides flanked by 3'-3' and 5'
      5' phosphodiester linkages from the perspective of the salient NMR techniques
      employed to shed light on the structural and dynamic properties of these
      sequences. Research into this class of synthetic alpha-/beta-oligonucleotides
      containing mixed strand disposition may have medical relevance given their
      recently documented efficacy as antisense therapeutics.

PMID- 9923710
TI  - Solid-state NMR studies of proteins: the view from static 2H NMR experiments.
AB  - The application of solid-state 2H NMR spectroscopy to the study of protein and
      peptide structure and dynamics is reviewed. The advantages of solid-state NMR for
      the study of proteins are considered, and the particular advantages of solid
      state 2H NMR are summarized. Examples of work on the integral membrane protein
      bacteriorhodopsin, and the membrane peptide gramicidin, are used to highlight the
      major achievements of the 2H NMR technique. These examples demonstrate that
      through the use of oriented samples, it is possible to obtain both structural and
      dynamic information simultaneously.

PMID- 9923711
TI  - Solid-state 2H NMR study of methyl-d3-cobalamin.
AB  - A solid-state 2H NMR study of methyl-d3-cobalamin has been performed as a
      function of temperature to provide information concerning the character and
      energetics of the motion performed by this unique bioorganometallic methyl group.
      Analysis of the 2H NMR line shape indicates that the methyl group undergoes rapid
      three-fold rotation, and that the Co-C-2H angle lies between 105.9 and 109.5
      degrees. Determination of the spin-lattice relaxation times T1 shows that the
      relaxation is anisotropic, consistent with a "jumping" motion of the methyl group
      rather than rotational diffusion. This also provides the activation energy to
      methyl jumps as 8.3 +/- 1.3 kJ/mol. It is proposed that this energetic barrier
      may be a useful probe of changes in the electronic character of the Co-C bond
      that accompany the biological role of this molecule in such enzymes as methionine
      synthase.

PMID- 9923712
TI  - Recent developments in solid-state nuclear magnetic resonance of quadrupolar
      nuclei and applications to biological systems.
AB  - Recent advances in nuclear magnetic resonance (NMR) methodology and improvements
      in high-field NMR instrumentation have generated a new wave of research interests
      in the application of solid-state NMR to the study of quadrupolar nuclei. These
      developments now permit increasingly complex biological systems to be probed by
      quadrupolar NMR. In this review I describe a few recent developments in NMR
      studies of quadrupolar nuclei and demonstrate the potential of solid-state
      quadrupolar NMR in the study of biological systems. In particular, I discuss the
      application of solid-state NMR of (17)O, 67Zn, 59Co, 23Na, and 39K nuclei with a
      prognosis for future work.

PMID- 9923713
TI  - Solid-state NMR studies of magnetically aligned phospholipid membranes: taming
      lanthanides for membrane protein studies.
AB  - The addition of lanthanides (Tm3+, Yb3+, Er3+, or Eu3+) to a solution of long
      chain phospholipids such as dimyristoylphosphatidylcholine (DMPC) and short-chain
      phospholipids such as dihexanoylphosphatidylcholine (DHPC) is known to result in
      a bilayer phase in which the average bilayer normal aligns parallel to an applied
      magnetic field. Lanthanide-doped bilayers have enormous potential for the study
      of membrane proteins by solid-state NMR, low-angle diffraction, and a variety of
      optical spectroscopic techniques. However, the addition of lanthanides poses
      certain challenges to the NMR spectroscopist: coexistence of an isotropic phase
      and hysteresis effects, direct binding of the paramagnetic ion to the peptide or
      protein of interest, and severe paramagnetic shifts and line broadening. Lower
      water concentrations and larger DMPC/DHPC ratios than those typically used in
      bicelles consistently yield a single oriented bilayer phase that is stable over a
      wide range of temperature (approximately 35-90 degrees C). Among the above choice
      of lanthanides, Yb3+ is found to give minimal paramagnetic shifts and line
      broadening at acceptably low concentrations necessary for alignment (i.e.,
      Yb3+/DMPC mole ratios equal to or greater than 0.01). Finally, the addition of a
      phospholipid chelate, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-
      diethylenetriaminepent aacetic acid, is observed to significantly reduce
      paramagnetic broadening and presumably prevent direct association of the peptide
      with the lanthanide ions.

PMID- 9923714
TI  - Polyelectrolyte-induced domains in lipid bilayer membranes: the deuterium NMR
      perspective.
AB  - Domain formation in lipid bilayer membranes can occur through electrostatic
      interactions between charged lipids and oppositely charged polyelectrolytes, such
      as proteins or polynucleic acids. This review describes a novel method for
      examining such domains in lipid bilayers, based on 2H NMR spectroscopy. The 2H
      NMR spectrum of choline-deuterated phosphatidylcholine is sensitive to, and
      reports on, lipid bilayer surface charge. When a charged lipid bilayer is exposed
      to an oppositely charged polyelectrolyte, the latter binds electrostatically to
      the bilayer surface and attracts charged lipids into its vicinity. The resulting
      inhomogeneous charge distribution produces overlapping 2H NMR subspectra arising
      from phosphatidylcholine within charge-enriched versus charge-depleted regions.
      Such spectral details as the quadrupolar splittings and the relative intensities
      of the subspectra permit a complete analysis of the domain composition, size,
      and, within limits, lifetime. Using 2H NMR, domain formation in lipid bilayer
      membranes can be observed with both cationic and anionic polyelectrolytes,
      whether of natural or synthetic origin. Domain size and composition prove to be
      sensitive to the detailed chemical structure of both the polyelectrolyte and the
      charged lipids. Within the domains there is always a stoichiometric anion/cation
      binding ratio, indicating that the polyelectrolyte lies flat on the membrane
      surface. The amount of phosphatidylcholine within the domain varies as a function
      of its statistical availability, in accordance with the predictions of a recent
      thermodynamic model of domain formation. When the molecular weight of the
      polyelectrolyte is varied, the domain size alters in accordance with the
      predictions of classical polymer physics. As expected for a predominantly
      electrostatic phenomenon, the observed domains dissipate at high ionic strength.

PMID- 9923715
TI  - Interaction between lipid bilayers and a new class of antineoplastic agents
      derived from arylchloroethylurea: a 2H solid-state NMR study.
AB  - We have investigated the interaction between a new class of antineoplastic agents
      derived from arylchloroethylurea (CEU) and model membrane of
      dimyristoylphosphatidylcholine by deuterium nuclear magnetic resonance
      spectroscopy. The results indicate that the drug incorporates in the bilayer and
      causes an increase of the lipid acyl chain order, this effect being greater close
      to the interfacial region of the lipid bilayer. The increase in ordering is
      dependent on the nature (degree of ramification, length of the alkyl chain, and
      presence of a sulfur atom) as well as on the position of the R substituent and is
      correlated with the cytotoxicity of the drugs. More specifically, the more
      cytotoxic drugs, such as 4-sec-butyl CEU, are those having a bulky ramified
      substituent and those for which the ordering effect on the lipid bilayer is the
      smallest. On the other hand, the ordering effect is greater and seen all along
      the lipid acyl chains for the long-chain CEUs, such as n-hexadecyl CEU, which
      have been shown to have very weak cytotoxic activity. Finally, the results
      obtained as a function of the drug concentration indicate that the ordering
      effect is seen for lipid to drug molar ratios as low as 20:1.

PMID- 9923716
TI  - Diagnosis of cancer in humans by 1H NMR of tissue biopsies.
AB  - We describe methodology for the diagnosis of human cancer, at high levels of
      accuracy, sensitivity, and specificity, by 1H NMR of tissue biopsies. This method
      is made robust and accurate by careful specimen preparation, and by multivariate
      analysis of spectral data. Examples are presented for the diagnosis of cancer of
      the prostate gland and the ovary. The potential for use of these methods
      noninvasively, in vivo, is shown to be very positive.

PMID- 9923717
TI  - Human cerebral neoplasms studied using MR spectroscopy: a review.
AB  - Of primary central nervous system tumors treated each year, the majority are
      glioma, followed by meningioma and then pituitary adenoma. While the use of
      magnetic resonance (MR) and computed tomographic imaging is well established in
      the diagnosis and management of such tumors, these techniques have a limited role
      in determining the metabolic state, either prior to or following therapy.
      Multinuclear MR spectroscopy, on the other hand, provides information on tumor
      metabolism and the effect of therapy on tumor viability. This paper reviews MR
      spectroscopic studies performed on patients with central nervous system tumors
      and discusses the impact that such studies have had on tumor diagnosis and
      management.

PMID- 9923718
TI  - A review of in vivo 1H magnetic resonance spectroscopy of cerebral ischemia in
      rats.
AB  - A number of metabolic alterations are initiated by cerebral ischemia including
      dramatic increases in lactate concentration, decreases in N-acetylaspartate,
      choline, and creatine concentrations, as well as changes in amino acid levels. A
      review of proton nuclear magnetic resonance spectroscopy studies of focal and
      global cerebral ischemia in rats is presented here. In particular, studies in
      neonatal rats have shown that a continued elevation of lactate levels without
      recovery after hypoxia-ischemia or a decrease in N-acetylaspartate concentration
      at any time are indicative of deleterious outcome. Studies of the effect of
      temperature on ischemic damage in a model of focal ischemia showed that outcome
      improved with mild hypothermia. Again, lack of recovery of lactate upon
      reperfusion was shown to be indicative of poor outcome. Dichloroacetic acid was
      used to treat rats with focal ischemic damage. Animals subjected to transient
      ischemia that were treated with dichloroacetic acid showed significant decreases
      in lactate concentration.

PMID- 9923719
TI  - The role of the N-acetylaspartate multiplet in the quantification of brain
      metabolites.
AB  - N-Acetylaspartate, whose methyl singlet is the primary magnetic resonance marker
      of neuronal dysfunction, also gives rise to a sequence-dependent, strongly
      coupled multiplet that overlaps the resonances of several other metabolites.
      Results are presented in this paper of a full numerical calculation of the
      response of the strongly coupled aspartate multiplet of N-acetylaspartate to a
      PRESS pulse sequence employing practical slice-selective pulses. These
      calculations, confirmed by experiments on phantoms, demonstrate the ability to
      predict the dependence of the response of strongly coupled spins on pulse design,
      as well as on interpulse evolutions, thereby facilitating a more rigorous
      comparison of the use of spectral fitting routines employed to extract metabolite
      concentrations on different instruments.

PMID- 9923720
TI  - Effect of temperature on the kinetics of lactate production and clearance in a
      rat model of forebrain ischemia.
AB  - To investigate the effect of brain temperature on metabolic perturbations during
      and following forebrain ischemia, localized 1H magnetic resonance spectroscopy
      was used to measure the kinetics of lactate production and clearance in a rat
      model of 12- or 20-min forebrain ischemia (two-vessel occlusion with hypotension)
      at a brain temperature of either 34.5 +/- 0.5 degrees C or 37.5 +/- 0.5 degrees
      C. During ischemia, lactate production was modeled with apparent first order
      kinetics. Hypothermia did not affect the rate or the extent of lactate production
      during ischemia. Upon reperfusion, a delay in the decrease of the cerebral
      lactate level was found in the normothermia groups. Such a delay was absent in
      hypothermia groups, which may reflect faster resumption of cerebral oxidative
      metabolism upon reperfusion in the hypothermic animals. The rate constant for
      lactate clearance postischemia was larger for normothermic animals and for the 20
      min ischemia groups, perhaps because of increased blood-brain barrier
      permeability following more severe ischemia.

PMID- 9923721
TI  - Cardiac magnetic resonance spectroscopy.
AB  - The article reviews cardiac magnetic resonance spectroscopy (MRS) in Canada. 31P
      MRS has been used to study cardiac energetics and intracellular pH in hearts
      subjected to ischemia-reperfusion and to evaluate the effects of pharmacological
      interventions. 23Na, 87Rb, and 7Li MRS have provided unique probes to study ion
      balance and fluxes in intact tissue under normal and stressful physiological
      conditions. 1H MRS has been used to monitor the accumulation of lactate and
      lipids in hearts subjected to ischemia-reperfusion and follow the effects of diet
      on cardiac lipid levels and function. The isolated rat heart has been used most
      commonly to study the effects of pharmacological agents on energy balance, pH,
      ion fluxes, and contractile function of the heart subjected to ischemia
      reperfusion. The pig heart has been developed as an alternative to the rodent
      heart because its metabolism is more similar to that of the human heart. Human
      atrial appendages have been useful in evaluating the effects of preservation
      strategies (temperature, composition of preservation solutions) on energy levels.
      The pig heart model has been useful in evaluating the effects of preservation
      solutions on cardiac function of hearts destined for transplantation. An isolated
      blood-perfused pig heart model has been developed to assess the effects of
      cardioplegic strategies on the preservation of contractile function of hearts
      following surgery on the heart. An in vivo canine model has been used to study
      myocardial infarction and the effects of therapies to reduce the infarct zones
      and areas of the heart at risk of infarction. Studies of human hearts in vivo
      have provided insight into the metabolic adaptations that occur in individuals
      living at high altitudes.

PMID- 9923722
TI  - Noninvasive assessment of pharmaceutical intervention during myocardial ischemia
      reperfusion in a canine model using two-dimensional 31P chemical shift imaging.
AB  - The metabolic effects during myocardial ischemia and sustained reperfusion of the
      antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored
      with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish
      any correlation between metabolic changes and infarct size. Spectroscopy followed
      changes in high-energy phosphate concentrations and myocardial intracellular pH
      during 2 h of left anterior descending coronary artery occlusion and 3 subsequent
      weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA
      enhanced magnetic resonance imaging was used to assess the extent of myocardial
      injury (infarct size). Microspheres were used to document the zone at risk and
      the success of reperfusion. Whereas diltiazem appeared to reduce the derangement
      in high-energy phosphates during coronary occlusion, there was no significant
      change in infarct size when compared with a previously studied control group.
      Propranolol, which produced a lesser decline in pH during occlusion and smaller
      pH changes during early reperfusion, was associated with a significant reduction
      in the degree of tissue necrosis (compared with controls). There was an inverse
      correlation (r = -0.51) between the change in myocardial pH (occlusion end to
      immediate reperfusion) and the recovery index (an index of myocardial salvage).
      By 1 h into reperfusion, there was a stronger inverse correlation between pH and
      infarct size (r = -0.75), implying a protective effect of delaying pH recovery
      during early reperfusion and indicating the potential use of this parameter as a
      predictor of tissue viability.

PMID- 9923723
TI  - Magnetic resonance imaging of regenerating and dystrophic mouse muscle.
AB  - Magnetic resonance imaging allows serial visualization of living muscle.
      Clinically magnetic resonance imaging would be the first step in selecting a
      region of interest for assessment of muscle disease state and treatment effects
      by magnetic resonance spectroscopy. In this study, magnetic resonance imaging was
      used to follow dystrophy and regeneration in the mdx mouse, a genetic homologue
      to human Duchenne muscular dystrophy. It was hypothesized that images would
      distinguish normal control from mdx muscle and that regenerating areas
      (spontaneous and after an imposed injury) would be evident and evolve over time.
      T2-weighted images of hind-limb muscles were obtained on anaesthetized mice in a
      horizontal bore 7.1-T experimental magnet. Magnetic resonance images of mdx
      muscle appeared heterogeneous in comparison to homogeneous images of control
      muscle. Foci of high intensity in mdx images corresponded to dystrophic lesions
      observed in the histologic sections of the same muscles. In addition, it was
      possible to follow chronologically the extent of injury and repair after an
      imposed crush injury to mdx muscle. These results should make it possible to
      obtain meaningful magnetic resonance spectra from particular regions of interest
      in muscle as viewed in magnetic resonance images (i.e., regenerating,
      degenerating, normal muscle) acquired during neuromuscular diseases and treatment
      regimens.

PMID- 9923724
TI  - Chronic ethanol administration alters hepatic rates of glycerol phosphorylation
      and glycerol 3-phosphate oxidation: a dynamic in vivo 31P magnetic resonance
      spectroscopy study.
AB  - We used dynamic in vivo 31P magnetic resonance spectroscopy to noninvasively
      study the metabolism of glycerol by the liver in living rats, as a means of
      detecting subtle metabolic changes induced by chronic ethanol consumption. Rats
      subjected to chronic ethanol consumption and their pair-fed controls were given a
      metabolic load of glycerol (0.75 or 1.3 mL glycerol x kg body mass(-1), i.p. or
      i.v) under normoxic or hyperoxic (98% O2) conditions. Changes in the level of
      glycerol 3-phosphate were followed in situ by monitoring the hepatic 31P
      phosphomonoester resonance every 7 or 13 min for up to 330 min. When challenged
      with a large dose of glycerol, chronic ethanol-treated rats exhibited less
      accumulation of glycerol 3-phosphate than controls, independent of the route of
      administration of the glycerol or whether the two groups were fasted or fed. For
      example, 1.3 mL glycerol x kg(-1) i.v. under normoxic conditions resulted in a
      two-fold increase in phosphomonoester in ethanol-treated rats compared with a
      five-fold increase in controls. The ethanol-treated rats also showed a slower
      rate of phosphorylation of glycerol and slower oxidation of glycerol 3-phosphate
      than controls, indicating decreased activities of the glycerol kinase and
      glycerol 3-phosphate dehydrogenase steps, and hence slower glycerol utilization.
      The rate of glycerol utilization was dose and oxygen concentration dependent.
      Kinetic analysis indicated that the chronic ethanol-induced decrease in the
      glycerol 3-phosphate dehydrogenase reaction was due to a decreased rate of NADH
      reoxidation in the liver, likely owing to a decrease in oxygen supply or
      utilization in the ethanol-treated rats. These observations support the
      hypothesis of pre-existing hypoxia in rat liver after chronic ethanol
      administration. This study demonstrates the utility of dynamic in vivo 31P
      magnetic resonance spectroscopy in following the metabolism of a glycerol load as
      a sensitive, nonperturbing, and potentially clinically applicable test of liver
      function.

PMID- 9923725
TI  - The effect of dietary flaxseed supplementation on organic anion and osmolyte
      content and excretion in rat polycystic kidney disease.
AB  - Progression of chronic renal failure in the Han:SPRD-cy rat polycystic kidney
      disease is associated with renal depletion of citric acid cycle metabolites and
      betaine. Amelioration of this disease by a soy protein diet is associated with
      retention of citric acid cycle anions, despite increased excretion, and
      preservation of tissue levels of betaine. As we have recently found that modest
      dietary supplementation with flaxseed preserves renal function and reduces
      histologic injury in the Han:SPRD-cy rat, we undertook a high-resolution 1H NMR
      spectroscopic study of urine and renal tissue extracts from Han:SPRD-cy rats to
      explore the renal biochemical consequences of a flaxseed diet. There was no
      significant dietary effect upon organic anion, methylamine, or osmolyte excretion
      in healthy animals. There was increased citrate excretion in Han:SPRD-cy rats fed
      flaxseed. Urinary ammonium excretion did not differ, suggesting that the observed
      increase in citrate excretion was not due to an alkaline effect of diet. Tissue
      extract studies revealed that disease amelioration was associated with tissue
      retention of succinate and betaine. Amelioration of Han:SPRD-cy rat polycystic
      kidney disease by diet is associated with alteration in the handling of citric
      acid cycle metabolites. Betaine may have a metabolic role in the reduction of
      chronic renal injury.

PMID- 9923726
TI  - Spatial and temporal resolution of functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging has become an invaluable tool for cognitive
      neuroscience, despite the fact that many of the physiological mechanisms giving
      rise to the effect are not well understood. We review the known biochemical and
      physiological basis of the technique and discuss how, within the noted limits,
      one might fully exploit the spatial and temporal resolution that is intrinsic to
      the very high magnetic fields that we use for human studies. This noninvasive
      brain mapping technique relies on the changes in blood oxygenation, blood volume,
      and blood flow, and we discuss some of the issues influencing the effects of
      these hemodynamic parameters on image intensity.

PMID- 9923727
TI  - 1997 Sir William Refshauge Lecture. Skeletal muscle glucose metabolism during
      exercise: implications for health and performance.
AB  - Skeletal muscle glucose uptake and metabolism are major determinants of whole
      body glucose metabolism in response to exercise and insulin stimulation. An
      understanding of the mechanisms responsible for increased muscle glucose uptake
      under these conditions is crucial for identifying strategies that enhance insulin
      action and exercise performance. Regular exercise, by favourably influencing the
      intramuscular determinants of glucose uptake, enhances insulin action. For this
      reason, it is recommended in the prevention and management of disease states that
      are characterised by insulin resistance ("metabolic syndrome"). Increased
      skeletal muscle glucose uptake, as a consequence of carbohydrate ingestion,
      maintains carbohydrate supply to contracting muscle, at a time when glycogen
      levels are reduced, and is associated with enhanced performance. Thus, both
      health and exercise performance are influenced by the metabolism of glucose
      within skeletal muscle.

PMID- 9923728
TI  - The effect of a high-carbohydrate diet on the skill performance of midfield
      soccer players after intermittent treadmill exercise.
AB  - This study examined the effect of a high-carbohydrate diet on the performance of
      dribbling and shooting skills of recreational soccer players. Six male midfield
      soccer players first completed 60 minutes of intermittent treadmill exercise,
      followed either by a mixed or a high-carbohydrate diet for 48 hours. A modified
      Zelenka Functional Performance Test was then administered, followed by the
      intermittent treadmill exercise and another skills test. Subjects then repeated
      the protocol two weeks later under the alternative dietary regime. Blood samples
      were obtained pre exercise and after each procedure for Hematocrit and
      concentrations of hemoglobin, plasma glucose and lactate. Heart rate was recorded
      during and after each procedure. Repeated measures MANOVA revealed (1) the skill
      performance was not impaired by the intermittent treadmill exercise (p > 0.05);
      (2) the high-carbohydrate diet did not increase the ability of players to shoot
      or dribble (p > 0.05); (3) a significant increase in heart rate during the post
      treadmill exercise skill test compared with that during the pre treadmill
      exercise test (p < 0.05); (4) a significant order by time effect for hematocrit
      (p < 0.05); (5) no significant differences in plasma glucose, plasma lactate or
      hemoglobin concentrations between tests (p > 0.05); and (6) a significant
      decrease in body mass from pre to post dietary regime within both conditions (p <
      0.05). It is speculated that either (1) muscle glycogen depletion may not impair
      the ability of the player to execute game skills; (2) an alternative fatigue
      mechanism such as dehydration or increased lactate production may be causative
      factors in the reduction in skill performance; or (3) the treadmill protocol
      employed failed to induce a degree of glycogen depletion or fatigue large enough
      to cause a significant fall in skill performance.

PMID- 9923729
TI  - The duration of predicting trials influences time to fatigue at critical power.
AB  - The present study compared times to fatigue at CP which had been calculated from
      relatively long duration predicting trials. With eight recreationally active
      males (mean age +/- SE = 18.6 +/- 2.1 years) having first cycled to fatigue on
      five occasions at different fixed work rates, CP was calculated in three ways: 1.
      using data from the three lowest exercise intensities (CPl); 2. using data from
      all five exercise intensities (CPa); and 3. using data from the highest three
      exercise intensities (CPh). Although CP was calculated using a linear and a three
      parameter non-linear model, there were insufficient suitable data to complete the
      latter analysis. After three days and over an eight day period, the subjects
      cycled for up to 60 minutes at each of the three CPs calculated using the linear
      model. Analysis revealed that despite high linearity with the five-point work
      time regression (average r2=0.996), CPl, CPa and CPh significantly differed to
      each other (268 +/- 17.5W; 285 +/- 12.1W; 321 +/- 8.8W respectively; p<0.05).
      Significant differences were also found between times to fatigue at CPl, CPa and
      CPh (42.9 +/- 3.9, 39.9 +/- 4.6 and 34.4 +/- 2.7 minutes respectively; p<0.05).
      The data show that when CP is calculated using a linear work-time regression,
      time to fatigue at CP is significantly influenced by the duration of predicting
      trials. Moreover, exercise at CP could only be maintained for 43 minutes despite
      CP being calculated from predicting trials averaging between 10 and 25 minutes.

PMID- 9923730
TI  - The relationship between aerobic fitness and both power output and subsequent
      recovery during maximal intermittent exercise.
AB  - The primary aim of the study was to establish a link between aerobic adaptation
      and both the recovery from maximal short duration exercise, and the ability to
      maintain power output in a subsequent bout. The question as to whether the
      aerobic adaptations facilitating recovery are centrally or peripherally located
      was also examined. Male university level rugby and soccer players (n=20)
      volunteered for the study. Mean (SD) age, mass and maximal oxygen uptake (VO2
      max) was 21.9 (1.8) years, 84.7 (12.7) kg and 52.7 (6.9) ml x kg(-1) x min(-1)
      respectively. Subjects completed six 15s maximal intensity sprints (90s active
      recovery) on a Monark friction braked cycle ergometer. A significant relationship
      (r=-.49, P=0.03) was obtained between VO2 max (mL x kg(-1) x min(-1)) and the
      percent drop-off in mean power in bouts 5 and 6 compared with bout 1. A
      correlation of r=-.62 (P=0.002) was obtained between VO2 max (mL x kg(-1) x min(
      1)) and the percent drop off in peak power in bouts 5 and 6 compared with bout 1.
      A significant correlation was obtained between arterial venous oxygen difference
      and the drop in mean power (r=-.54, P=0.02) but not with the drop in peak power
      (r=-.22, P=.36). There was no significant relationship between cardiac output and
      the drop in mean power (r=-.16, P=.51) or the drop in peak power (r=-.02, P=.94).
      Percent drop-off in oxygen consumption, when compared with the first, in the
      second (RVO2(30-60)), third (RVO2(60-90)), fourth (RVO2(90-120)) and fifth
      (RVO2(120-150)) 30s time periods of recovery following the intermittent protocol
      was calculated. Correlations between VO2 max (ml x kg(-1) x min(-1)) and these
      variables were (r=.51, P=-0.03), (r=.44, P=0.06), (r=.63, P=-0.003) and (r=.6,
      P=0.007) respectively. Consequently it was concluded that maximal oxygen uptake
      particularly the peripheral component, is an important determinant of the ability
      to perform intermittent exercise of this nature and to recover between bouts.

PMID- 9923731
TI  - A survey of injuries sustained in the game of touch.
AB  - Three hundred and forty-five Touch football players were retrospectively surveyed
      to determine the nature and incidence of injuries sustained over a one year
      period. The definition of injury was that it prevented playing or training for at
      least one week. A total of 177 injuries were sustained by 117 players who
      participated in a total of 1043 hours of playing and training each week. The
      injury rate was 4.85/1000 hours of playing or training which was less than in
      other football codes. This rate was significantly more (p < 0.05) among males and
      no relationship was evident based on representative or training status. 71% of
      injuries were to the lower limb. 23% of all injuries involved the ankle. Less
      than 3% of injuries affected the head or neck. 54% of injuries were considered
      mild in that they only prevented playing or training for less than two weeks.
      Only 17% of injuries were stated to have been caused by contact with another
      player. This study found that the injury rate in Touch was much less than in
      other football codes.

PMID- 9923732
TI  - The effects of eccentric exercise on neuromuscular function of the biceps
      brachii.
AB  - This study investigated the effects of a bout of exercise-induced muscle damage
      on strength and motor skill of the elbow flexor muscles. Eight subjects performed
      35 maximal isokinetic eccentric elbow flexions at 90 degrees sec(-1) and maximal
      voluntary contraction (MVC) force, surface electromyography (EMG), plasma
      creatine kinase (CK) and tracking error associated with a one-dimensional elbow
      flexion/extension visuomotor pursuit task were studied at intervals up to 28 days
      after exercise. Subjects showed a post-exercise decline in MVC (mean = 63 +/- 11%
      (s.d.) of pre-exercise after 1 day, p<0.02) and were still significantly weaker
      at 21 days. The delayed-onset plasma CK rise and the absence of any quantitative
      change in surface EMG suggest that the observed weakness was related to muscle
      fibre damage. Tracking performance decreased in all subjects with the greatest
      tracking error occurring 1 day post-exercise (mean = 127% +/- 20% of control
      value, p<0.02). There was a significant negative correlation between strength and
      tracking performance following exercise (r2 = 0.724). The results demonstrate
      that performance in activities requiring fine motor control will be impaired for
      a number of days following a bout of damaging exercise.

PMID- 9923733
TI  - Reproducibility of knee laxity assessment results using the dynamic cruciate
      tester.
AB  - The purpose of the study was to examine reproducibility of knee laxity
      measurements obtained using the Dynamic Cruciate Tester (DCT) from day-to-day,
      set-to-set, and trial-to-trial. In Part I, peak anterior tibial translation (ATT)
      was assessed for 1 anterior cruciate ligament (ACL) deficient and 16 control
      subjects during two sets of three active trials (maximal isometric quadriceps
      contractions) and three passive trials (240 N load) conducted over four
      consecutive days. In Part II, peak ATT was recorded for 12 chronic ACL deficient
      subjects during one set of five active and five passive trials within one day.
      Results were analysed using mixed repeated measures ANOVA designs with intraclass
      reliability coefficients (ICC) calculated from the ANOVA results. There were no
      significant differences in the mean peak ATT results among the four tests days or
      between the two test sets conducted within a day, with ICC ranging from R1 =
      0.939 to 0.980. It was concluded peak ATT measurements obtained using the DCT
      were reproducible from day-to-day and set-to-set. A significant main effect of
      trial was found on both active (F(2,32) = 13.93; p < 0.001) and passive (F(2,32)
      = 57.21; p < 0.001) peak ATT results. It was therefore recommended a full
      pretrial should be conducted before knee laxity assessment using the DCT to
      ensure reproducible results.

PMID- 9923734
TI  - Purification of the glycoprotein G from viral haemorrhagic septicaemia virus, a
      fish rhabdovirus, by lectin affinity chromatography.
AB  - A new method for the isolation of glycoprotein G from viral haemorrhagic
      septicaemia virus (VHSV), a fish rhabdovirus, was developed by using affinity
      chromatography with immobilized Concanavalin A (ConA). The glycoprotein G was
      isolated from detergent solubilized concentrated virions and from large-volume
      virion-free supernatants from VHSV infected cells (soluble form). The purity
      achieved was higher than 85%. The estimated recovery of the initial glycoprotein
      G present in the virions was between 20 and 50%. These glycoprotein G
      preparations showed the presence of about 30% of trimers by ultracentrifugation,
      reacted with antibodies to the phosphatidylserine binding domain (p2) in a pH
      dependent manner by ELISA and bound phosphatidylserine in a pH-dependent manner
      by solid-phase binding assays. These data suggest that ConA purified glycoprotein
      G conserved most of its native properties and conformation.

PMID- 9923735
TI  - Detection of each of the causal agents of groundnut rosette disease in plants and
      vector aphids by RT-PCR.
AB  - Detection of the three agents of groundnut rosette disease (groundnut rosette
      assistor virus, groundnut rosette virus and its satellite RNA) in plants and
      vector aphids by reverse transcription-polymerase chain reaction (RT-PCR) is
      reported. Three procedures for extraction of total RNA from groundnut were
      tested, of which two were found to be useful in giving RNA of sufficient quality
      for RT-PCR. Of these two, the total RNA extraction kit supplied by Qiagen was
      found to be the most versatile for extraction of all three agents from individual
      vector aphids (Aphis craccivora). Both groundnut rosette assistor virus and
      groundnut rosette virus could be detected from total RNA extracted from a single
      aphid that had been exposed to either green or chlorotic rosette-infected
      groundnut plants. They could be detected in aphids stored in 70% ethanol for up
      to 30 days at room temperature. However, satellite RNA could be amplified only
      when total RNA extracted from two or more aphids was used. Groundnut rosette
      assistor virus, groundnut rosette virus and its satellite RNA were detected by RT
      PCR in aphids that had been exposed only to groundnut rosette diseased plants
      containing all three agents. The potential of RT-PCR in studying certain key
      issues of rosette disease epidemiology is discussed.

PMID- 9923736
TI  - Affinity purification of HC-Pro of potyviruses with Ni2+-NTA resin.
AB  - The HC-Pro of zucchini yellow mosiac virus (ZYMV) was found to bind to Ni2+-NTA
      resin with or without His-tagging. The binding stringency was similar to that
      observed in proteins with a zinc finger motif like the HC-Pro. Using this
      characteristic we developed an efficient and rapid method (2-3 h) for
      purification of the HC-Pro of several potyviruses. A dominant protein of about
      150 kDa was extracted and identified as the HC-Pro of ZYMV by means of
      immunoblotting. About 150 microg of HC-Pro were partially purified from the
      soluble fraction of 1 g of leaves. High titers of HC-Pro protein were obtained
      from plants infected with four potyviruses [ZYMV, watermelon mosaic virus II
      (WMVII), papaya ringspot virus (PRSV) and turnip mosaic virus (TuMV)]. The HC
      Pros of potato virus Y (PVY) and tobacco vein mottling virus (TVMV) did not bind
      to the Ni2+-NTA resin. The ZYMV-HC-Pro purified by the Ni2+-NTA resin could bind
      in vitro to ZYMV virions blotted onto a membrane. All the HC-Pros which had been
      successfully purified by the Ni2+-NTA resin were bound in vitro to membrane
      blotted ZYMV coat protein. However, only the HC-Pros of ZYMV and WMVII were able
      to mediate aphid transmission of purified ZYMV virions. The purification
      procedure described herein is efficient and convenient, and enables HC-Pro for a
      number of potyviruses to be obtained in larger amounts and at higher purity than
      possible by means of most existing methods, based on ultracentrifugation.

PMID- 9923737
TI  - Optimization of packaging of adeno-associated virus gene therapy vectors using
      plasmid transfections.
AB  - Adeno-associated Virus (AAV) is attracting wide attention as a potential human
      gene therapy vector. The advantages of this vector system are that it is
      naturally defective, it readily integrates into the target cell's genome and is
      considered to be nonpathogenic. AAV infects a wide variety of cell and tissue
      types. The major disadvantages of the vector are its small size and the labor
      intensive procedures required to prepare large amounts of the vector for clinical
      studies. In this manuscript we have systematically tested a number of variables
      in the packaging procedure to determine the optimal conditions for successful
      vector preparation. Using an AAV vector that expresses the green fluorescent
      protein and the most commonly used packaging plasmid, pAAV/Ad, we determined the
      optimal conditions for; lysis of the transfected cultures, ratio of packaging to
      vector plasmids, day of harvest after transfection, storage conditions,
      multiplicity of infection of helper adenovirus, and the time of adenovirus
      infection. These results have important relevance for investigators that are
      using AAV vectors for heterologous gene transfer studies.

PMID- 9923738
TI  - Detection of GB virus C RNA by GBV-C LCx and two PCR assays with primers from the
      5' non-coding and NS5B region.
AB  - The objective of this study was to compare the sensitivity of three different
      reverse transcriptase-polymerase chain reaction (RT-PCR) based tests, for
      detection of GB virus C (GBV-C) RNA. One commercial and two 'in house' RT-PCR
      assays were employed in the testing of serum samples from 114 chronic hepatitis C
      infected individuals. A part of the 5' non-coding region (5'NCR) of the GBV-C
      genome was amplified by the GBV-C LCx assay (Abbott) and one of the 'in house' RT
      PCR tests. In the other 'in house' RT-PCR a segment of the NS5B region was
      amplified. The 'in house' assays included the use of internal controls that were
      co-amplified with use of the same outer PCR primers as the virus targets. The GBV
      C LCx from Abbott and 5'NCR 'in house' PCR tests detected 28 and 27 GBV-C
      positive individuals, respectively. The sample positive only in the LCx test was
      confirmed by the 'in house' 5'NCR RT PCR using an increased virus input. In
      comparison, the NS5B 'in house' PCR test detected 24 of the GBV-C positive
      samples. One sample showed no amplification of internal controls/virus target in
      the 5'NCR 'in house' PCR and another samples was amplification negative in the
      NS5B PCR. The PCR assays with primers from the 5'NCR of the virus genome e.g. the
      GBV-C LCx, were more sensitive compared with RT-PCR using primers from the NS5B
      region. The GBV-C LCx seemed to be the most sensitive and robust assay. Internal
      controls included in the 'in house' assays identified two samples with failure of
      the amplification.

PMID- 9923739
TI  - An efficient way to introduce unique restriction endonuclease sites into a
      baculovirus genome.
AB  - Recombinant baculoviruses which can be linearized at unique sites with
      restriction endonucleases can greatly facilitate the construction of other
      recombinants including baculovirus expression vectors and site-specific mutants.
      We designed a strategy to introduce unique restriction endonuclease sites at
      virtually any location in a baculovirus genome. The unique sites were first
      introduced onto a transfer plasmid which also contained in the vector portion of
      the plasmid an E. coli lacZ gene and a Sse8387I site, a sequence which is not
      found in the viral genome. Cotransfection of the transfer plasmid and circular
      viral DNA generated single-crossover recombinant viruses which could be
      distinguished as blue plaques in the presence of X-gal, a chromogenic indicator
      for lacZ. Single-crossover recombinants were purposefully isolated and propagated
      to generate double-crossover recombinants. Viral DNA isolated from the mixed
      virus population was digested with Sse8387I to linearize only the single
      crossover viral DNA; double-crossover recombinants in the progeny viral
      population resulting from transfection with the Sse8387I-linearized viral DNA
      mixture were thus highly enriched, making the task of screening much easier. To
      demonstrate the feasibility of this approach, we introduced Bsu36I sites into the
      orf24 and the vlf-1 regions of Autographa californica multiple-nucleocapsid
      nuclear polyhedrosis virus (AcMNPV) to generate recombinant viruses vncBsuorf24
      and vncBsuvlf1, respectively. Both recombinant viruses were obtained by screening
      only ten plaques. This method should also be applicable to other kinds of
      mutations and may be applicable to other double-stranded DNA viruses.

PMID- 9923741
TI  - Quantitation of herpes simplex viral DNA in Vero cells for evaluation of an
      antiviral agent using the polymerase chain reaction.
AB  - A method for quantitation of the DNA of Herpes simplex virus type 2 (HSV-2)
      infected Vero cells by the polymerase chain reaction (PCR) was developed. This
      method allowed recognition of several molecules of viral DNA among the total DNA
      extracted from cells. The method could be applied to a very large range (10(-0)
      10(-7)) of initial amounts of template. Products of PCR were collected after each
      cycle for kinetic analysis. Products were subjected to electrophoresis and
      amplified bands were stained with ethidium bromide. The intensity of fluorescence
      of each band was measured with a charge-coupled device (CCD) image analyzer. The
      time course of increases in the relative yield of viral DNA was determined. Two
      fold amplification of viral DNA occurred each 6-h cycle from 7 h after infection.
      Using this method, the yields of viral DNA after treatment with the drug
      acyclovir (ACV) at 0.1 and 2 microg/ml were about 1/10 and 1/80 of those from
      nontreated infected cells, respectively. These results indicate that this method
      makes clear the inhibitory effect of ACV on the synthesis of viral DNA.

PMID- 9923740
TI  - Strongly enhanced sensitivity of a direct anti-HIV-1/-2 assay in seroconversion
      by incorporation of HIV p24 ag detection: a new generation vironostika HIV Uni
      Form II.
AB  - The clinical sensitivity of the current anti-HIV assays is based for an important
      part on their reactivity with seroconversion panels. The most sensitive assay
      closes the seroconversion window as much as possible, thereby reducing the risk
      of transmitting false negative donations obtained from individuals infected
      recently. Because of the absence of anti-HIV antibodies during the early phase of
      infection, the seroconversion window can be narrowed partially by detection of
      HIV p24 Ag. To achieve this, the highest affinity anti-p24 binding antibodies
      were selected with BlAcore and applied in a direct assay format. To achieve
      optimal conditions for the anti-HIV part of the assay the HIV specific antigens
      viral HIV-1 gp160, HIV-2 gp36 and HIV-1 group O gp41 peptides were used. These
      antigens and antibodies were applied for microELISA coating as well as in the
      conjugate pearl, which is present in the well of the microELISA plate. The
      (analytical) anti-HIV-1/-2 and anti-HIV-1 group O sensitivity of this new assay,
      Vironostika HIV Uni-Form II Ag/Ab, is at least at the level of the current
      Vironostika HIV Uni-Form II plus O. When compared to the Vironostika HIV Uni-Form
      II plus O, the seroconversion window is narrowed by 1-2 weeks due to the
      incorporation of HIV p24 Ag detection. The level of reactivity of the anti-HIV
      and HIV Ag detection part can be improved by about a factor 2 by applying
      continuous shaking during sample incubation. Initial studies suggested that the
      specificity of the assay is identical to that of the Vironostika HIV Uni-Form II
      plus O, namely > 99.9%. Monitoring of proper execution of the assay handling
      steps was facilitated by implementing a purple dye in the conjugate pearl.
      Colourless specimen diluent changes into a green fluid upon dissolving of the
      conjugate pearl and turns subsequently into blue/purple upon sample addition.
      These visual changes can also be determined by spectrophotometric measurement at
      620 nm.

PMID- 9923742
TI  - Culture amplification in human colon adenocarcinoma cell line (CaCo-2) combined
      with an ELISA as a supplementary assay for accurate diagnosis of rotavirus.
AB  - Culture amplification in colon adenocarcinoma cell line (CaCo-2) combined with
      enzyme immunoassay (Pathfinder ELISA) was developed as a supplementary tool for
      rotavirus diagnosis. One hundred and thirty stools in which results by
      polyacrylamide gel electrophoresis (PAGE) were in agreement with those obtained
      by ELISA were amplified in the CaCo-2 cell line. After the first passage 100%
      specimens were revealed as positive by ELISA. This result was confirmed by PAGE
      and direct electron microscopy (EM) which increased the rates of rotavirus
      detection up to 100% after the third and fifth cell passages, respectively. All
      of the amplified negative stools were confirmed as negative. Among discordant
      results, three of the eight specimens positive by ELISA but negative by PAGE were
      confirmed as true positive after the third cell passage. False positive ELISA
      results could be discarded when the samples were culture amplified and retested
      by the same ELISA. Using the CaCo-2 amplification-ELISA as supplementary assay,
      sensitivity and specificity were 1.000 and 0.953 for ELISA and 0.917 and 1.000
      for PAGE, respectively. The combined CaCo-2 cell line amplification-immunoassay
      method proved to be suitable both to evaluate increase in sensitivity of newly
      developed rotavirus assays and for rotaviral amplification before antigen assays.

PMID- 9923743
TI  - Simplified procedure for fractionation and structural characterisation of complex
      mixtures of N-linked glycans, released from HIV-1 gp120 and other highly
      glycosylated viral proteins.
AB  - HIV-1 gp120 is heavily glycosylated containing 24 N-glycosylation sites, and this
      makes elucidation of the significance of glycans at individual glycosylation
      sites a difficult task. A procedure is described where a complex mixture of
      biologically radiolabelled glycans of gp120, derived from a relatively small
      number of virus-infected cells may be characterized by a combination of N
      glycanase release, single lectin separation, and normal phase HPLC (NP-HPLC). The
      method was applied in analysis of three N-linked glycosylation sites essential
      for the in vivo priming of T-cells, specific for an epitope in their vicinity
      (Sjolander, S., Bolmstedt, A., Akerblom, 1996. Virology 215, 124-133.). The
      carbohydrate compositions of wild type gp120 and of mutant variants gp120 lacking
      one, two, or all of these three active N-linked glycans were analysed. Cells were
      infected with r-vaccinia virus expressing wild-type gp120 or mutated gp120, or
      were infected with HIV-1BRU (wild type) or mutant virus variants. HIV-1
      glycoproteins were purified by immunosorbent affinity chromatography and released
      glycans were separated on lectins, then analysed with NP-HPLC. Our data showed
      that the structural composition of glycans occupying two of the three
      glycosylation sites was heterogeneous but the site located adjacent to the T-cell
      epitope was equipped with one large, high mannose-type structure (> 11 units)
      with the capacity to cover a substantial part of the gp120 surface.

PMID- 9923744
TI  - A novel expression system based on host-range expansion of baculovirus.
AB  - A host range expanded recombinant Autographa californica multiple-nucleocapsid
      nucleopolyhedrosis virus AcMNPV/r2 was obtained by cotransfection of the bacmid
      DNA from Escherichia coli DH10Bac along with a plasmid pBmH-M containing HindIII
      M fragment of Bombyx mori nuclear polyhedrosis virus (BmNPV) genomic DNA. A
      recombinant transposon vector carrying a mutant green fluorescent protein gene
      (GFP) and a polyhedrin gene was constructed. Transposition was carried out in
      both E. coli DH10Bac and E. coli DH10BmH, which contains AcMNPV/r2 and a helper
      plasmid. Recombinant DNAs were transfected into Sf-9 cells to generate
      recombinant virus AcMNPV/r3 and AcMNPV/r4 respectively. Viral stock of AcMNPV/r4
      was then infected into Bombyx mori cells (BmN) and Bombyx mori larvae (silkworm).
      Analysis shows that GFP was highly expressed in Bombyx mori larvae. This
      expression system, is practicable therefore for mass production of foreign gene
      products.

PMID- 9923745
TI  - Development and analysis of a tick-borne encephalitis virus infectious clone
      using a novel and rapid strategy.
AB  - In less than 1 month we have constructed an infectious clone of attenuated tick
      borne encephalitis virus (strain Vasilchenko) from 100 microl of unpurified virus
      suspension using long high fidelity PCR and a modified bacterial cloning system.
      Optimization of the 3' antisense primer concentration was essential to achieve
      PCR synthesis of an 11 kb cDNA copy of RNA from infectious virus. A novel system
      utilising two antisense primers, a 14-mer for reverse transcription and a 35-mer
      for long PCR, produced high yields of genomic length cDNA. Use of low copy number
      Able K cells and an incubation temperature of 28 degrees C increased the genetic
      stability of cloned cDNA. Clones containing 11 kb cDNA inserts produced colonies
      of reduced size, thus providing a positive selection system for full length
      clones. Sequencing of the infectious clone emphasised the improved fidelity of
      the method compared with conventional PCR and cloning methods. A simple and rapid
      strategy for genetic manipulation of the infectious clone is also described.
      These developments represent a significant advance in recombinant technology and
      should be applicable to positive stranded RNA viruses which cannot easily be
      purified or genetically manipulated.

PMID- 9923746
TI  - Differentiation of rice tungro bacilliform virus strains by restriction analysis
      and DNA hybridization.
AB  - Rice tungro bacilliform virus (RTBV) is one of the two viruses that cause tungro
      disease. Four RTBV strains maintained in the greenhouse for 4 years, G1, G2, Ic,
      and L, were differentiated by restriction fragment length polymorphism (RFLP)
      analysis of the native viral DNA. Although strains G1 and Ic had identical
      restriction patterns when cleaved with Pst1, BamHI, EcoRI, and EcoRV, they can be
      differentiated from strains G2 and L by EcoRI and EcoRV digestion. These same
      endonucleases also differentiate strain G2 from strain L. When total DNA extracts
      from infected plants were used instead of viral DNA, and digested with EcoRV,
      identical restriction patterns for each strain (G2 and L) were obtained from
      roots, leaves, and leaf sheaths of infected plants. The restriction patterns were
      consistent from plant to plant, in different varieties, and at different times
      after inoculation. This technique can be used to differentiate RTBV strains and
      determine the variability of a large number of field samples.

PMID- 9923747
TI  - Detection of antibodies to equine arteritis virus by enzyme linked immunosorbant
      assays utilizing G(L), M and N proteins expressed from recombinant baculoviruses.
AB  - Indirect enzyme linked immunosorbant assays (ELISAs) utilizing the three major
      structural proteins (M, N, and G(L)) of equine arteritis virus (EAV) expressed
      from recombinant baculoviruses were developed. A large panel of sera collected
      from uninfected horses, and from animals experimentally and naturally infected
      with EAV or vaccinated with the modified live virus vaccine against equine viral
      arteritis, were used to characterize the humoral immune response of horses to the
      three major EAV structural proteins. The data suggest that the M protein was the
      major target of the equine antibody response to EAV. The responses of individual
      animals varied and ELISAs that utilized individual EAV structural proteins were
      not reliable for detecting antibodies in all sera that contained neutralizing
      antibodies to EAV. An ELISA based on a cocktail of all three EAV structural
      proteins, however, was used successfully to detect antibodies in most equine sera
      that were positive in the standard serum neutralization assay following natural
      or experimental EAV infection (100% specificity, 92.3% sensitivity). In contrast,
      this ELISA did not reliably detect antibodies in the sera of vaccinated horses.
      EAV frequently causes a persistent infection in stallions and all sera from
      carrier stallions evaluated in this study had obvious reactivity with the N
      protein, whereas seropositive non-carrier stallions, mares and geldings did not
      respond consistently to the N protein.

PMID- 9923748
TI  - Minimizing DNA recombination during long RT-PCR.
AB  - Recent developments have made it possible to reverse transcribe RNA and amplify
      cDNA molecules of > 10 kb in length, including the HIV-1 genome. To use long
      reverse transcription combined with polymerase chain reaction (RT-PCR) to best
      advantage, it is necessary to determine the frequency of recombination during the
      combined procedure and then take steps to reduce it. We investigated the
      requirements for minimizing DNA recombination during long RT-PCR of HIV-1 by
      experimenting with three different aspects of the procedure: conditions for RT,
      conditions for PCR, and the molar ratios of different templates. We used two
      distinct HIV-1 strains as templates and strain-specific probes to detect
      recombination. The data showed that strategies aimed at completing DNA strand
      synthesis and the addition of proofreading function to the PCR were most
      effective in reducing recombination during the combined procedure. This study
      demonstrated that by adjusting reaction conditions, the recombination frequency
      during RT-PCR can be controlled and greatly reduced.

PMID- 9923749
TI  - Generation of influenza transfectants using purified recombinant nucleocapsid
      protein.
AB  - Affinity-purified type A influenza virus nucleocapsid protein expressed by a
      recombinant baculovirus vector was used in in vitro RNA transcription reactions
      to create RNP complexes containing a synthetic influenza A virus NS gene. When
      used in transfection assays, the baculovirus-expressed NP was shown to be
      biologically active allowing the efficient isolation of transfectant viruses
      containing the artificially-introduced NS gene. The results demonstrate that NP
      is the only virion protein necessary in the reconstituted RNP complexes used for
      transfection thus eliminating the need for purified RNP complexes containing
      active polymerase.

PMID- 9923750
TI  - Isolation of HIV-1 RNA from plasma: evaluation of seven different methods for
      extraction (part two).
AB  - Some new commercial methods for the extraction of viral RNA have been introduced
      recently. In addition to the study published previously (Verhofstede, C.,
      Reniers, S., Van Wanzeele. F., Plum J., 1996. AIDS 8, 1421-1427), seven different
      methods (four newly developed and three reference methods) for extraction of HIV
      1 RNA from plasma have been evaluated. The RNA preparation method that gave the
      best results (acceptable reproducibility, highest sensitivity, reasonable price,
      fast and easy to perform), was the QIAamp Viral RNA kit from QIAgen. The High
      Pure Viral RNA Kit (Boehringer Mannheim) as well as the non-commercialised
      extraction kits were also very sensitive. The non-commercial tests seem less
      suitable for routine use and for the processing of large number of samples. Two
      methods, RNA Insta-Pure LS (Eurogentec) and PANext RNA extraction kit 1 (NTL,
      PANsystems GmbH) are not adapted for HIV plasma extraction. The single step
      methods using glass fibre or silica column are rapid (from 60 to 75 min depending
      on the number of wash steps) and although the price is high they are cheaper than
      the Boom extraction methods: High Pure Viral RNA Kit (Boehringer Mannheim)
      ($3.3/sample), QIAamp Viral RNA Kit (Qiagen) ($3.6/sample), Boom extraction
      ($5/sample). The Qiagen kit is the only kit that combines sensitivity with
      reproducibility, it is commercialised, rapid and affordable in price and can be
      automated. For most of the methods evaluated the inter-test variability was
      acceptable (mean variation coefficient between duplicate extractions varied
      between 26.4 and 48.6%).

PMID- 9923751
TI  - Identification of S-(1,2-dichlorovinyl)glutathione in the blood of human
      volunteers exposed to trichloroethylene.
AB  - Healthy male and female human volunteers were exposed to 50 ppm or 100 ppm
      trichloroethylene (Tri) by inhalation for 4 h. Blood and urine samples were taken
      at various times before, during, and after the exposure period for analysis of
      glutathione (GSH), related thiols and disulfides, and GSH-derived metabolites of
      Tri. The GSH conjugate of Tri, S-(1,2-dichlorovinyl)glutathione (DCVG), was found
      in the blood of all subjects from 30 min after the start of the 4-h exposure to
      Tri to 1 to 8 h after the end of the exposure period, depending on the dose of
      Tri and the sex of the subject. Male subjects exposed to 100 ppm Tri exhibited a
      maximal content of DCVG in the blood at 2 h after the start of the exposure of
      46.1 +/- 14.2 nmol/ml (n = 8), whereas female subjects exposed to 100 ppm Tri
      exhibited a maximal content of DCVG in the blood at 4 h after the start of the
      exposure of only 13.4 /- 6.6 nmol/ml (n = 8). Pharmacokinetic analysis of blood
      DCVG concentrations showed that the area under the curve value was 3.4-fold
      greater in males than in females, while the t1/2 values for systemic clearance of
      DCVG were similar in the two sexes. Analysis of the distribution of individual
      values indicated a possible sorting, irrespective of gender, into a high- and a
      low-activity population, which suggests the possibility of a polymorphism. The
      mercapturates N-acetyl-1,2-DCVC and N-acetyl-2,2-DCVC were only observed in the
      urine of 1 male subject exposed to 100 ppm Tri. Higher contents of glutamate were
      generally found in the blood of females, but no marked differences between sexes
      were observed in contents of cyst(e)ine or GSH or in GSH redox status in the
      blood. Urinary GSH output exhibited a diurnal variation with no apparent sex- or
      Tri exposure-dependent differences. These results provide direct, in vivo
      evidence of GSH conjugation of Tri in humans exposed to Tri and demonstrate
      markedly higher amounts of DCVG formation in males, suggesting that their
      potential risk to Tri-induced renal toxicity may be greater than that of females.

PMID- 9923752
TI  - Endocrine and reproductive function in ewes exposed to the organochlorine
      pesticides lindane or pentachlorophenol.
AB  - The effects of lindane (LIN, gamma-hexachlorocyclohexane) and pentachlorophenol
      (PCP) on reproduction and general endocrine function were examined in breeding
      ewes as a model for wild and domestic ungulates, which may be exposed to low
      levels of pesticides that are potential endocrine-disrupting chemicals. Ewes (n =
      13/group) were fed either a control untreated diet (CON), or a diet treated with
      LIN (1 mg/kg/d) or PCP (1 mg/kg/d) during the 5 wk prior to mating and throughout
      pregnancy and lactation. Mating response, ovulation rate, follicle and corpus
      luteum size, gestation length, pregnancy rate, lambing rate, and lamb birth
      weight were recorded. After weaning, 6 ewes from each group were bled at 15-min
      intervals for 8 h during the day and night and for 1 h before and 5 h after i.v.
      administration of gonadotropin-releasing hormone, thyroid-stimulating hormone
      (TSH), and adrenocorticotropin, to measure serum concentrations of luteinizing
      hormone, follicle-stimulating hormone, thyroxine (T4), and cortisol. Ewes were
      then killed and endocrine tissues examined histologically. Pregnancy rate as a
      result of matings taking place at the synchronized estrus was significantly
      decreased by the lindane treatment However, PCP and lindane did not markedly
      affect any other aspect of reproductive function studied. In PCP-treated ewes,
      serum concentrations of T4 were significantly reduced compared to control ewes
      during the day and night; however, the T4 response to TSH was not altered by PCP
      treatment. No other measured endocrine parameters were consistently affected by
      lindane or PCP. Thyroid follicle size was significantly increased in the LIN and
      PCP ewes compared to the control ewes. Low serum concentrations of T4 in the PCP
      ewes may have resulted in increased TSH secretion and increased thyroid follicle
      size. In conclusion, although pesticide treatments had no serious adverse effects
      on reproductive function in breeding ewes, PCP reduced T4 concentration, which in
      the long term could influence reproductive and general performance.

PMID- 9923753
TI  - Region-specific decrease of dopamine and its metabolites in brains of mice given
      ergotamine.
AB  - Ergot alkaloids (EA) such as the ergopeptine alkaloid ergotamine (ET) are
      adrenergic, dopaminergic, and serotonergic agents. The objective of this
      experiment was to investigate regional brain neurotransmitter alterations caused
      by EA. Male BALB/c mice were treated s.c. daily with ergotamine tartrate for 10 d
      at 0 (saline), 0.4, 2, 10, or 50 mg/kg body weight. Twenty-four hours after the
      last treatment, animals were sacrificed and brains dissected. Regional
      concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and
      metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole
      3-acetic acid (5-HIAA) were measured by high-performance liquid chromatography
      (HPLC). Moreover, selected organ weights and plasma prolactin (PRL) were
      determined. Dopamine concentration was significantly reduced by ET at all doses
      in the striatal and hypothalamic regions. A reduction of the DA metabolite HVA
      occurred in striatum at only the highest dose, whereas in the hypothalamus both
      HVA and DOPAC were markedly reduced. Concentrations of NE, MHPG, 5-HT, and 5-HIAA
      were not affected by treatment in these regions. In the cerebellum, MHPG was
      significantly elevated at the 50 mg/kg dose. No effect of treatment was observed
      in the cerebrum, medulla, and midbrain. Further, no treatment-related differences
      in plasma PRL and organ weights other than a significant liver weight decrease at
      intermediate doses were found. Therefore, the effects of ET were predominantly
      upon DA metabolism in the corpus striatum and hypothalamus. The reductions in DA,
      HVA, and DOPAC indicate decreased DA synthesis.

PMID- 9923754
TI  - Effect of styrene on monoamine oxidase B activity in rat brain.
AB  - Previous studies have indicated that workers exposed to styrene present a
      decreased activity of platelet monoamine oxidase B (MAO B), suggesting that this
      biochemical assay may represent a biomarker for styrene-induced neurotoxicity.
      This study was undertaken to determine whether exposure to styrene would cause
      changes in MAO B activity in the target organ--the brain. Groups of rats were
      exposed to styrene by inhalation at concentrations of 300 ppm for 4 wk or 50 ppm
      for 13 wk. Both treatments caused significant decreases of MAO B activity in
      several brain areas, while MAO A activity was not affected. Decreases in MAO B
      activity were also found in brainstem of rats given styrene (400 mg/kg) or
      styrene oxide (100 mg/kg) by i.p. injection for 2 wk. Styrene, styrene oxide, and
      other styrene metabolites (mandelic acid, phenylglyoxylic acid, and styrene
      glycol) had no direct inhibitory effect on brain MAO B activity when tested in
      vitro. These results indicate that exposure to low concentrations of styrene
      alters MAO B activity in rat brain, suggesting that the observed changes in human
      platelets may reflect alterations in the nervous system.

PMID- 9923755
TI  - Focusing attention on cognitive impairment in spinocerebellar ataxia.

PMID- 9923756
TI  - Continuing medical education in neurology: an archives of neurology initiative.

PMID- 9923757
TI  - Late-onset myasthenia gravis: a changing scene.
AB  - The prevalence of myasthenia gravis (MG) among middle-aged and older patients has
      increased. Patients with early-onset MG live longer than before, but there is
      also an increase in late-onset MG (onset of the disease after the age of 50 years
      in patients with no clinical or paraclinical evidence of a thymoma).
      Epidemiological data support using the age of 50 years to separate early- and
      late-onset MG. The main immunological difference between early- and late-onset MG
      is the presence of antibodies to muscle titin, which are detected in
      approximately 50% of patients with late-onset MG. Treatment of late-onset MG has
      to be tailored both to the age of the patient and to the immunological findings
      of that particular form of MG.

PMID- 9923758
TI  - Stem cell technology for basic science and clinical applications.

PMID- 9923759
TI  - Diagnostic criteria for Parkinson disease.
AB  - The clinical diagnosis of Parkinson disease (PD) is based on the identification
      of some combination of the cardinal motor signs of bradykinesia, rigidity,
      tremor, and postural instability, but few attempts have been made to develop
      explicit diagnostic criteria. We propose a clinical diagnostic classification
      based on a comprehensive review of the literature regarding the sensitivity and
      specificity of the characteristic clinical features of PD. Three levels of
      diagnostic confidence are differentiated: Definite, Probable, and Possible. The
      diagnoses of Possible and Probable PD are based on clinical criteria alone.
      Neuropathologic confirmation is required for the diagnosis of Definite PD in
      patients with the clinical diagnosis of Possible or Probable PD. Criteria for
      histopathologic confirmation of PD are also presented.

PMID- 9923761
TI  - The Heidenhain variant of Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: To investigate whether typical neuropathological and radiological
      findings can be identified in patients with the clinical diagnosis of the
      Heidenhain variant of Creutzfeldt-Jakob disease (CJD). DESIGN: Case study. The
      clinical symptoms, neuropathological findings, electroencephalograms, magnetic
      resonance images, and cerebrospinal fluid samples of 14 Heidenhain cases were
      evaluated. Neuropathological changes were compared with those in a group of 14
      patients with ataxia as the leading clinical sign. SETTING: A university
      hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance
      Study. PATIENTS: Medical records of 169 neurologically examined patients with
      prospectively classified and neuropathologically confirmed CJD were analyzed.
      MAIN OUTCOME MEASURE: Difference in neuropathological and radiological findings
      between patients with the Heidenhain variant and other patients with CJD.
      RESULTS: Of 169 patients with confirmed CJD, 20% showed characteristic clinical
      findings such as blurred vision, visual field restriction, metamorphopsia, or
      cortical blindness. Disease course of the Heidenhain group, as compared with the
      group of all patients with definite CJD, was significantly shorter (5.7 months vs
      7.5 months; P=.02, t test). Neuropathological examination of patients with the
      Heidenhain variant showed most pronounced changes in the occipital lobe but less
      damage in the cingulate gyrus and basal ganglia compared with 14 patients with
      CJD who had ataxia as the leading clinical sign. Eleven (92%) of 12 genetically
      analyzed Heidenhain cases were homozygous for methionine at codon 129 of the
      prion protein gene (PRNP). In 9 of 9 cases, the 14-3-3 protein was present. In 7
      (78%) of 9 cases, the level of neuron-specific enolase was elevated, with a
      concentration above 35 ng/mL. Periodic sharp-wave complexes were observed in 11
      (78%) of the 14 cases. In 7 (63%) of 11 patients, magnetic resonance images
      showed symmetric hyperintensities in the basal ganglia in the T2- and proton
      weighted sequence. In 4 of 11 cases the T2- and proton density-weighted images
      showed a pronounced signal increase confined to the gray matter of the occipital
      and visual cortex. Isolated atrophy of the visual cortex was noticeable in 2 of
      11 cases. CONCLUSIONS: The clinical presentation of the Heidenhain variant of CJD
      was shown to correlate with the neuropathological findings of gliosis and nerve
      cell loss. In patients with visual disorders of unclear origin and signs of
      dementia, the differential diagnosis of a Heidenhain variant of CJD must be taken
      into consideration.

PMID- 9923760
TI  - Spinocerebellar ataxia type 2: clinical features of a pedigree displaying
      prominent frontal-executive dysfunction.
AB  - BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is a recently delineated cause
      of autosomal dominant cerebellar ataxia type I. The basic clinical neurologic
      features of SCA2 have been described in the literature, but neuropsychological
      features have not, despite statements that some patients became demented.
      OBJECTIVE: To describe the clinical and neuropsychological features of patients
      from a pedigree with SCA2. PATIENTS AND METHODS: We studied 8 affected members of
      an Australian pedigree of northern Italian origin with autosomal dominant
      cerebellar ataxia type I caused by SCA2. Patients underwent clinical neurologic
      examination and abbreviated neuropsychological testing, while some also underwent
      magnetic resonance imaging. The results were compared with pooled results from
      previously published studies of patients with SCA2. RESULTS: The pedigree
      displayed anticipation, with earlier onset in later generations, and there was an
      inverse correlation between repeat number and age at onset. The principal
      difference from other clinical reports of SCA2 was our finding of unequivocal
      frontal-executive dysfunction in 5 of 6 individuals who could be tested
      quantitatively, despite Mini-Mental State Examination scores in the nondemented
      range. This feature did not appear to correlate with either repeat size or
      duration of illness. CONCLUSIONS: In light of a recent report of frontal
      executive dysfunction in spinocerebellar ataxia type III, we postulate that this
      pattern may be common to the autosomal dominant cerebellar ataxias and frequently
      may be overlooked because of the insensitivity of routine screening tests such as
      the Mini-Mental State Examination.

PMID- 9923762
TI  - A pedigree with a novel presenilin 1 mutation at a residue that is not conserved
      in presenilin 2.
AB  - OBJECTIVE: To disclose a novel mutation of the presenilin 1 (PS1) gene
      responsible for early-onset Alzheimer disease and to clarify genotype-phenotype
      correlation that should help to establish the function of this protein.
      BACKGROUND: The PS1 and presenilin 2 (PS2) genes carry missense mutations in
      families with Alzheimer disease. The PS1 and PS2 proteins have similar
      structures, and all presently known mutations are in nucleotides coding for amino
      acids that are conserved between the 2 presenilins. METHODS: Sequence and
      restriction fragment length polymorphism analyses of PS1 gene of DNA from a
      pedigree with early-onset Alzheimer disease. RESULTS: Sequence analysis disclosed
      a novel PS1 mutation in a pedigree of Japanese origin with early-onset Alzheimer
      disease. This mutation, which is predicted to cause a missense substitution of
      lysine for glutamic acid, occurred at codon 123 of PS1 that was not a conserved
      residue in PS2. The 2 patients of this pedigree shared an early clinical
      phenotype consisting of later-onset, progressive aphasia, but preserved
      visuospatial ability, which was indistinguishable from those of other PS1
      associated Alzheimer disease cases. CONCLUSION: These results demonstrate that a
      missense mutation in a region not conserved between PS1 and PS2 can cause
      Alzheimer disease.

PMID- 9923763
TI  - Decreases in T-cell tumor necrosis factor alpha binding with interferon beta
      treatment in patients with multiple sclerosis.
AB  - OBJECTIVE: To investigate the effects of interferon beta treatment on T-cell
      tumor necrosis factor alpha (TNF-alpha) binding (which is a possible marker for T
      cell-dependent immune function) in patients with multiple sclerosis. DESIGN: The
      TNF-alpha binding on T lymphocytes from patients with stable relapsing-remitting
      multiple sclerosis was assayed before and 3 and 6 months after the start of
      treatment with interferon beta. SETTING: The study was performed on ambulatory
      patients in a tertiary care center. PATIENTS: Eighteen patients with clinically
      definite stable relapsing-remitting multiple sclerosis (13 women and 5 men; mean
      [+/-SD] age, 32.6+/-7.1 years) were selected consecutively. Clinical status was
      defined according to the Expanded Disability Status Scale. All patients were
      treated with 8 x 10(6) U of interferon beta-1b subcutaneously every other day.
      Eighteen age- and sex-matched healthy subjects, with no family history of
      neuropsychiatric disorders, served as controls. RESULTS: T lymphocytes from
      untreated patients with multiple sclerosis had significantly more TNF-alpha
      receptors than those from controls (mean+/-SE, 837+/-33 vs 135+/-5 receptors per
      cell). After 3 months of treatment with interferon beta-1b, they showed a
      significant decrease (P<.001) in TNF-alpha binding (452+/-29 receptors per cell).
      After 6 months, T-cell TNF-alpha maximal receptor numbers were even lower (345+/
      35 receptors per cell). CONCLUSION: Given that increased TNF-alpha binding might
      be linked to lymphocyte activation, our data demonstrate that a major effect of
      interferon beta-lb treatment is to decrease T-cell activation.

PMID- 9923764
TI  - T-cell apoptosis in inflammatory neuromuscular disorders associated with human
      immunodeficiency virus infection.
AB  - BACKGROUND: Apoptosis is one of the major mechanisms of CD4+ T-cell depletion in
      human immunodeficiency virus (HIV) infection. T cells in human inflammatory
      myopathies in HIV-negative individuals rarely undergo apoptosis. Currently, there
      is no information available concerning the fate of T cells in HIV-associated
      myositis and polyneuropathies. OBJECTIVE: To investigate whether apoptosis occurs
      in inflammatory lesions of muscle and nerve biopsy specimens of untreated HIV
      positive patients with neuromuscular disorders. METHODS: T-cell apoptosis was
      investigated in muscle and nerve specimens from 12 patients with HIV-associated
      polymyositis and 8 patients with HIV-associated inflammatory polyneuropathy.
      These were compared with specimens from 36 HIV-negative patients with other
      inflammatory myopathies and from 18 patients with inflammatory polyneuropathies.
      Apoptosis was assessed according to morphological criteria and with the use of in
      situ labeling methods. RESULTS: In none of the HIV-associated disorders did we
      observe a substantial proportion of apoptotic T cells as assessed by nuclear
      morphological findings and in situ labeling techniques. Fas expression was up
      regulated only in a few inflammatory cells. Positive labeling for Fas ligand was
      not associated with increased apoptosis of surrounding T cells. Nuclei of
      degenerating muscle fibers and macrophages did not show morphological signs of
      apoptosis and were not labeled by the tailing reaction. CONCLUSIONS: Similar to
      their idiopathic counterparts, in HIV-related polymyositis and inflammatory
      neuropathy, T-cell inflammation is not cleared by apoptosis. The observations are
      consistent with the non-self-limited nature of endomysial or endoneural
      inflammation and suggest that in HIV-positive patients, the T-cell elimination is
      differentially regulated in the lymphoid organs as compared with neuromuscular
      tissues.

PMID- 9923765
TI  - Peripheral nerve function in HIV infection: clinical, electrophysiologic, and
      laboratory findings.
AB  - OBJECTIVE: To determine the effects of immunodeficiency, nutritional status, and
      concurrent systemic disease on peripheral nerve function in acquired
      immunodeficiency syndrome. DESIGN: Survey of subjects infected with human
      immunodeficiency virus (HIV), recruited as part of a prospective study of
      neuromuscular complications of HIV infection. SETTING: A neuro-acquired
      immunodeficiency syndrome outpatient clinic in a university medical center.
      PATIENTS: A consecutive sample of 251 HIV-infected individuals. Primary care
      providers referred subjects to the study for evaluation of neurologic symptoms or
      for prospective neurologic assessment. MAIN OUTCOME MEASURES: Standardized
      history and neurologic examination, laboratory tests (complete blood cell count,
      serum albumin level, vitamin B12 level, and T-lymphocyte subsets), and
      electrophysiologic testing of sural, tibial, and ulnar nerves. RESULTS: The most
      frequent neurologic diagnosis was distal symmetrical polyneuropathy (DSP) (38%).
      The most common clinical features were nonpainful paresthesias (71%),
      abnormalities of pain and temperature perception (71%), and reduced or absent
      ankle reflexes (66%). Patients with DSP were significantly older (P=.009), and
      had lower CD4 lymphocyte cell counts (P=.004) and lower hemoglobin levels
      (P=.004) than those without DSP. Deterioration of values on nerve conduction
      studies, irrespective of the clinical diagnosis of DSP, was significantly
      correlated with low CD4 counts, aging, abnormal serum albumin and hemoglobin
      levels, and weight loss. Most of these factors co-correlated, and, with the
      exception of age, no single variable significantly accounted for changes in
      results of nerve conduction studies when the influence of other factors was
      eliminated. CONCLUSION: The combination of several factors, including age,
      immunosuppression, nutritional status, and chronic disease, contributes to distal
      peripheral nerve dysfunction in HIV infection.

PMID- 9923766
TI  - Multiple system atrophy: the putative causative role of environmental toxins.
AB  - BACKGROUND: Whereas a number of studies have investigated the putative role of
      environmental toxins in the pathogenesis of idiopathic Parkinson disease, the
      possibility of such a role in multiple system atrophy has received little
      attention. DESIGN AND SETTING: Review of records of patients examined in the
      Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of
      Medicine, Houston, Tex, from July 1, 1977, to February 4, 1998. PATIENTS: We
      reviewed 100 consecutive medical records of patients who satisfied the diagnostic
      criteria for multiple system atrophy formulated by the Consensus Committee of the
      American Autonomic Society and the American Academy of Neurology. INTERVENTION:
      The type and amount of toxin exposure were verified by history and examination of
      records whenever possible. Severity of parkinsonism was assessed by clinical
      rating scales. MAIN OUTCOME MEASURE: Development of multiple system atrophy after
      environmental toxin exposure. RESULTS: Eleven patients had a notable history of
      heavy exposure to environmental toxins. One patient with multiple system atrophy
      confirmed by postmortem evaluation was exposed to high concentrations of
      malathion, diazinon, and formaldehyde, while the other patients with multiple
      system atrophy had well-documented high exposures to agents including n-hexane,
      benzene, methyl isobutyl ketone, and pesticides. The case studied pathologically
      demonstrated extensive advanced glial changes, including glial cytoplasmic
      inclusions in deep cerebellar white matter, brainstem, cortex (superior frontal,
      insula) and putamen, with notable cell loss and depigmentation of the substantia
      nigra and locus ceruleus. CONCLUSION: While many studies report a possible role
      of environmental toxins in Parkinson disease, such a role is even more likely in
      multiple system atrophy, as this is a sporadic disease.

PMID- 9923767
TI  - Clinical correlates of vascular parkinsonism.
AB  - BACKGROUND: Parkinsonism may be due to other causes besides Parkinson disease
      (PD). Vascular parkinsonism (VP) has not been well defined and the clinical
      correlates of VP have not been clarified. OBJECTIVES: To seek evidence for or
      against the role of cerebrovascular disease in parkinsonism, and to identify
      clinical features that suggest a vascular origin. DESIGN: Retrospective chart
      review of patients with parkinsonism. A vascular rating scale was used to
      identify 2 patient groups, 1 with strong evidence of cerebrovascular disease
      (VP), and 1 with idiopathic PD. Clinical features of parkinsonism were then
      compared between the 2 patient groups. SETTING: A Movement Disorders Clinic,
      Baylor College of Medicine, Houston, Tex, a tertiary referral center. PATIENTS:
      Three hundred forty-six patients, 69 with VP and 277 with PD. RESULTS: The VP and
      PD groups were clearly differentiated in terms of evidence of cerebrovascular
      disease (P<.001 to P<.00001). Patients with VP were older, more likely to present
      with gait difficulty rather than tremor, and less likely to respond to the use of
      levodopa compared with patients with PD (P<.00001). Patients with VP were also
      significantly more likely to have predominant lower body involvement, postural
      instability, a history of falling, dementia, corticospinal findings, incontinence
      (P<.00001), and pseudobulbar effect (P<.05). CONCLUSIONS: These differences in
      clinical features suggest a different pathogenesis of parkinsonism in these 2
      patient groups. The strong evidence of cerebrovascular disease in the VP group
      and the differences in clinical features support the concept of VP as a distinct
      clinical entity. We conclude that compared with PD, patients with parkinsonism
      associated with vascular disease are more likely to present with gait difficulty
      and postural instability rather than tremor, have a history of stroke and risk
      factors for stroke, and fail to respond to levodopa therapy.

PMID- 9923768
TI  - Developmental deficits in adult patients with arteriovenous malformations.
AB  - BACKGROUND: Cerebral arteriovenous malformations (AVMs) are congenital masses of
      arteries and veins that appear to undergo an unclear "maturation" for many years.
      Using structured interviews, we compared developmental history of adult patients
      with AVM with a comparison group of patients with cerebral tumor or aneurysm.
      OBJECTIVE: To determine whether a remote history of developmental abnormality in
      adult patients with AVM might be an early marker of cerebral status. DESIGN:
      Adult patients with AVM and a comparison group of patients with cerebral aneurysm
      or low-grade tumor participated in a survey. SETTING: Urban medical school-based
      tertiary care center. PATIENTS: Forty-four randomly selected patients with AVM
      from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15
      randomly chosen patients from the institution's Cerebral Aneurysm Database and
      all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low
      grade tumor and who could be contacted. MAIN OUTCOME MEASURES: A brief,
      structured interview adapted from the Centers for Disease Control and Prevention
      for its 1994 study of the prevalence of learning disabilities in American
      children. We defined the positive occurrence of a condition as an affirmative
      answer to the question, " Did have (condition) during his/her school-age years?"
      Each patient was also asked if there had been any problems in the following skill
      areas: reading, writing, listening, speaking, attention, impulsivity,
      organization, mathematics, or drawing. The AVM size was calculated on the
      angiographic film by measuring its longest diameter in any dimension. RESULTS:
      Patients with AVM were significantly more likely to report a positive occurrence
      to any survey question (P<.05). Two thirds of all patients with AVM (66%)
      reported at least 1 skill difficulty during their school years, significantly
      more than the comparison group (P<.001). Neither the maximum AVM diameter nor the
      occurrence of hemorrhage as an adult differed between patients with AVM with and
      without early skill difficulty. CONCLUSIONS: Patients with AVM are more likely to
      report a developmental learning disorder than patients with tumor or aneurysm
      despite the absence of other neurologic symptoms of diseases not diagnosed for
      another 20 years. These data support the notion that disorders of behavioral and
      intellectual function are sensitive markers of early cerebral status.

PMID- 9923769
TI  - Marchiafava-Bignami disease: computed tomographic scan, 99mTc HMPAO-SPECT, and
      FLAIR MRI findings in a patient with subcortical aphasia, alexia, bilateral
      agraphia, and left-handed deficit of constructional ability.
AB  - OBJECTIVES: To report and discuss the neuropsychological deficits and
      neuroimaging findings in a patient with probable Marchiafava-Bignami disease.
      DESIGN AND METHOD: A right-handed woman with chronic alcoholism demonstrated
      mutism, impaired comprehension of spoken language, alexia, and right-handed
      agraphia. The syndrome of interhemispheric disconnection was manifested by left
      handed deficit of constructional ability and agraphia. The patient underwent
      brain computed tomographic scans, technetium 99 hexylmethylpropylene amineoxime
      single photon emission computed tomography, and magnetic resonance imaging (MRI)
      that also included fluid attenuated inversion recovery images. SETTING: Clinical
      neurology department. RESULTS: The patient's symptoms were related to scattered
      lesions of the corpus callosum and to extensive symmetrical lesions of the
      centrum semiovale. Only the latter were detected by computed tomographic scans.
      Results of single photon emission computed tomography did not show areas of focal
      hypoperfusion. Results of fast spinecho MRI showed all lesions were hyperintense
      in T1-weighted images and hypointense in T2-weighted images. Fluid attenuated
      inversion recovery images revealed that periventricular lesions had a hypointense
      core surrounded by a hyperintense rim; callosal lesions were still hyperintense.
      CONCLUSIONS: We believe that our patient's symptoms are due to the discontinuous
      affection of the corpus callosum and to the bilateral cutting of the outflow from
      the cortex. The MRI findings may be interpreted as indicating central necrosis
      and peripheral demyelination of periventricular lesions and demyelination of the
      corpus callosum. The combined use of fast spin echo and fluid attenuated
      inversion recovery MRI reproduced with more accuracy than fast spin echo MRI
      alone some features of Marchiafava-Bignami disease known from observations at
      autopsy.

PMID- 9923770
TI  - Isolated, chronic, epilepsia partialis continua in an HIV-infected patient.
AB  - BACKGROUND: The characteristic clinical feature of epilepsia partialis continua
      (EPC) is chronic focal myoclonus, usually involving the distal part of one
      extremity. A variety of pathogenetic factors have been implicated in EPC. In
      children, the most common cause is Rasmussen encephalitis; in adults, it is
      vascular disease or tumor involving the sensorimotor cortex. Epileptic seizures
      are a relatively common manifestation of central nervous system involvement in
      patients infected with human immunodeficiency virus (HIV), but, to our knowledge,
      isolated, chronic EPC has not been previously reported. OBJECTIVE: To describe a
      case of typical EPC in a patient infected with HIV. DESIGN AND SETTING: Case
      report from an epilepsy center. PATIENT: A 58-year-old man infected with HIV had
      continuous myoclonus that involved the right arm and was associated with
      intermittent motor seizures. The electroencephalographic findings were normal at
      the onset of the symptoms, but left central theta rhythm appeared later. Serial
      magnetic resonance imaging scans obtained over a 3-month period showed a
      progressively increasing left rolandic T2-weighted hypersignal. Histologic study
      of a stereotactic biopsy specimen demonstrated inflammation characterized by
      perivascular mononuclear cell infiltration. The only detectable cause was HIV
      infection. Immunocytochemical tests ruled out JC virus. Neuropsychological
      testing showed no evidence of cognitive impairment. An electroencephalographic
      electromyographic "back-averaging" study showed a reproducible transient left
      biphasic complex preceding the bursts by about 30 milliseconds on the C3 and F3
      electrodes, thus demonstrating that the myoclonus was of cortical origin. High
      dose corticosteroid (prednisone, 100 mg/d) and anti-HIV- 1 therapy led to marked
      radiological and clinical improvement. Infection with HIV enhances the risk of
      seizures, but, to our knowledge, this is the first reported case of
      "inflammatory" EPC. CONCLUSIONS: The present case suggests that the possibility
      of central nervous system involvement by HIV-1 should be taken into account in
      the diagnostic workup of patients with EPC. This case also indicates that
      treatment can be effective.

PMID- 9923771
TI  - "Toilet seat" sciatic neuropathy.

PMID- 9923772
TI  - Sleep and narcolepsy.

PMID- 9923774
TI  - Neurology International Partnership Program.

PMID- 9923773
TI  - Methodological pitfalls in evaluating clinical tests.

PMID- 9923775
TI  - Mohs micrographic excision of lentigo maligna using Mel-5 for margin control.

PMID- 9923776
TI  - Dermatopathology in Europe: dreams and realities.

PMID- 9923777
TI  - Clinical characteristics and long-term outcome of patients with generalized patch
      and/or plaque (T2) mycosis fungoides.
AB  - OBJECTIVES: To study the long-term results of treatment of patients with
      generalized patch and/or plaque mycosis fungoides and to identify clinical
      characteristics predictive of survival and response to treatment. DESIGN: A
      single-center, 35.5-year retrospective cohort analysis. SETTING: Private referral
      medical center. PATIENTS: One hundred seventy-six patients with generalized patch
      and/or plaque (T2) mycosis fungoides. MAIN OUTCOME MEASURES: Long-term actuarial
      survival and freedom-from-relapse results as calculated by the Kaplan-Meier
      method. RESULTS: The long-term (35.5-year) survival of patients with T2 mycosis
      fungoides is worse than the expected survival of a race-, age-, and sex-matched
      control population (P<.001). The median survival of the T2 group is 11.7 years.
      Patients younger than 58 years (median age) at presentation have a more favorable
      overall and disease-specific survival than the patients who are 58 years or older
      (P<.001 vs P<.025). Patient sex or race had no significant effect on overall
      survival. Patients who presented with palpable clinically significant lymph nodes
      (stage IIA) had long-term survival results similar to those without
      lymphadenopathy (stage IB), despite improved freedom-from-relapse outcome for
      patients with stage IB. Twenty-four percent of patients who progressed to more
      advanced disease had a lower complete response rate to initial therapy than did
      other patients (21% vs 65%) (P<.001). Patients who received total skin electron
      beam therapy had a better complete response rate than patients treated with
      topical mechlorethamine hydrochloride alone; the relapse-free results were
      superior in patients with a total dose of 30 Gy or higher and in patients who
      received topical mechlorethamine as adjuvant therapy following total skin
      electron beam therapy. Despite differences in freedom-from-relapse results among
      different treatment groups, long-term overall or disease-specific survivals were
      not significantly different. CONCLUSIONS: A significant proportion (24%) of
      patients with generalized patch and/or plaque (T2) mycosis fungoides experience
      disease progression to a more advanced clinical stage, and nearly 20% eventually
      die of the disease. Younger patients have a more favorable disease-specific long
      term outcome than patients who are older. Presence of lymphadenopathy (stage IIA)
      at diagnosis does not predict worse long-term survival outcome. Clinical features
      predictive of disease progression include initial lymphadenopathy (stage IIA) and
      lack of complete response to initial treatment. Despite superior complete
      response rate to a 30-Gy or higher dose of total skin electron beam therapy,
      topical mechlorethamine proves to be a cost-effective initial treatment for
      patients with T2 disease. The concept of an adjuvant therapy after irradiation is
      appealing, although it may not lead to improved long-term survival.

PMID- 9923778
TI  - Cutis marmorata telangiectatica congenita: clinical features in 35 cases.
AB  - OBJECTIVE: To evaluate the distribution of skin lesions, clinical features, and
      associated abnormalities in children with cutis marmorata telangiectatica
      congenita at onset and during follow-up. DESIGN: Retrospective survey of the
      available medical data with an average follow-up of 1 year 5 months (range, 0-7
      years). SETTING: Pediatric Dermatology Unit (Department of Dermatovenereology) of
      the Sophia Children's Hospital in Rotterdam, the Netherlands. PATIENTS: The
      diagnosis of cutis marmorata telangiectatica congenita was clinically established
      in 35 patients between July 1988 and February 1997. In 33 cases, the typical
      mottled, blue-violet pattern was present from birth and was readily visible at
      rest. In 2 cases, the skin lesions initially appeared less reticulated, mimicking
      a capillary malformation. RESULTS: The skin lesions were almost generalized in 4
      children (11%), whereas they were more localized in the other 31 children (89%).
      Associated anomalies, usually minor and sometimes questionable, were noted in 80%
      of the patients. Most patients showed a definite improvement of their mottled
      vascular skin lesions within 2 years. The lesions had totally disappeared, or
      only faded residual lesions remained. CONCLUSIONS: We believe that cutis
      marmorata telangiectatica congenita is a relatively mild condition. The prognosis
      is usually good, with minor associated anomalies. Improvement of the mottled,
      vascular pattern is usually observed within 2 years. We recommend careful
      clinical examination of all patients to exclude any associated anomalies.
      Patients should be referred to a neurologist or an ophthalmologist only if
      symptoms are present or if vascular lesions are present around the eyes.

PMID- 9923779
TI  - The prevalence of factor V Leiden mutation in patients with leg ulcers and venous
      insufficiency.
AB  - OBJECTIVES: To study the prevalence of factor V Leiden mutation in patients with
      chronic venous insufficiency and venous leg ulcers, compared with a control
      group, and to find out whether factor V Leiden mutation is more frequent in
      patients with chronic venous insufficiency and a history of deep venous
      thrombosis. DESIGN: A case control study. SETTING: Three outpatient
      dermatological clinics. PATIENTS: Ninety-two patients (37 men, 55 women) with
      venous leg ulcers and 53 control patients (23 men, 30 women). MAIN OUTCOME
      MEASURE: Factor V Leiden mutation. RESULTS: Factor V Leiden mutation was
      significantly more frequent in patients with chronic venous insufficiency and
      venous leg ulcers than in the control group (23% vs 7.5%; P=.03), and the
      patients with factor V Leiden mutation were more likely to have a history of
      venous thromboembolism (91% vs 48%, P=.002). Also, recurrent deep venous
      thrombosis (38% vs 14%) and recurrent leg ulcerations (9 episodes or more)
      occurred more frequently in the patients with factor V Leiden mutation (43% vs
      19%, P=.01). No difference was observed in venous refill time or in the presence
      of dermatoliposclerosis and atrophie blanche. CONCLUSIONS: Factor V Leiden
      mutation is more frequent in patients with venous leg ulceration than in the
      control group and the general population. Patients with factor V Leiden mutation
      have an increased risk of developing deep venous thrombosis and recurrent leg
      ulceration.

PMID- 9923780
TI  - Body-site distribution of melanocytic nevi in young Australian children.
AB  - OBJECTIVE: To investigate the body-site distribution of melanocytic nevi (MN)
      with respect to habitually and intermittently sun-exposed surfaces. DESIGN: Cross
      sectional survey of MN prevalence. SETTING: Townsville (19.16 degrees S),
      Queensland, Australia. PARTICIPANTS: Random sample of 506 1- to 6-year-old white
      children who were born and raised in Townsville (response, 87.6%). MAIN OUTCOME
      MEASURES: Site-specific counts and densities (number per square meter) of MN.
      RESULTS: Densities of MN of all sizes were highest on the outer forearms,
      followed by the outer upper arms, neck, and face. The feet had the lowest density
      of MN. Densities of MN of 2 mm or greater were highest on the upper arms and
      trunk. Boys had higher densities of MN of all sizes on the neck than girls (P =
      .002). Girls had higher densities of MN of 2 mm or greater on the lower legs (P =
      .006) and thighs (P = .005) than boys. Habitually sun-exposed body sites had
      higher densities, particularly of small MN, than relatively sun-protected sites,
      and larger MN were most prevalent on the intermittently exposed skin of the
      trunk. CONCLUSIONS: These children have higher total body and site-specific MN
      counts and densities than children from elsewhere, and their MN are distributed
      over the body in a way that implicates exposure to sunlight. As sun exposure in
      childhood and MN are risk factors for melanoma, intervention studies are required
      to determine if MN can be prevented.

PMID- 9923781
TI  - Mycophenolate is effective in the treatment of pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris is a potentially life-threatening autoimmune
      disease. Although combination therapies with prednisone and azathioprine are
      usually effective in controlling the disease, some patients either do not respond
      to this treatment or show early relapses. OBJECTIVE: To find out whether
      mycophenolate mofetil would be an effective drug in controlling pemphigus
      vulgaris in patients who failed initial treatment with azathioprine and
      prednisone. RESULTS: Twelve patients who were initially diagnosed as having
      pemphigus vulgaris and had relapsed while undergoing treatment with azathioprine
      (1.5-2 mg/kg of body weight) and prednisolone (2 mg/kg of body weight)
      subsequently received combination therapy with mycophenolate mofetil (2 x 1 g/d)
      and prednisolone (2 mg/kg of body weight per day). Eleven of the 12 patients
      responded to therapy and showed no relapse of their disease even after tapering
      of the steroid dose. One patient did not respond. Toxic effects were low with
      only mild gastrointestinal symptoms in 5 patients and mild lymphopenia (World
      Health Organization grade I) in 9 patients. During the 9- to 12-month follow-up,
      none of the 11 patients showed reappearance of pemphigus lesions. CONCLUSION:
      Treatment of pemphigus vulgaris with mycophenolate is a safe and effective
      treatment.

PMID- 9923782
TI  - Pulse intravenous cyclophosphamide therapy in pemphigus.
AB  - BACKGROUND: Adjuvant therapy is commonly used in pemphigus to mitigate the high
      morbidity and mortality associated with the use of corticosteroids and improve
      disease control. However, these adjuvant agents are not without adverse effects
      of their own, including an increased risk of malignancy with the use of oral
      immunosuppressives. Intravenous pulse cyclophosphamide, which may be more
      efficacious and less toxic than oral immunosuppressives, has been used
      successfully in the treatment of pemphigus. OBJECTIVE: To review 9 patients with
      severe or previously recalcitrant pemphigus who were treated with intravenous
      pulse cyclophosphamide therapy. RESULTS: Six of the 9 patients responded to
      therapy, with 2 patients achieving remission from skin lesions. Five patients
      were able to decrease their daily dose of prednisone, and 1 was able to
      discontinue the use of prednisone completely. Most patients experienced minimal
      or no adverse effects. CONCLUSIONS: Intravenous pulse cyclophosphamide may be an
      alternative treatment option in patients with pemphigus recalcitrant to standard
      therapy. The decreased cumulative dose of cyclophosphamide observed with monthly
      pulse doses may reduce the incidence of secondary malignancies when compared with
      continuous oral therapy. Controlled trials are needed to further evaluate the
      efficacy of this mode of therapy.

PMID- 9923783
TI  - Sweet's syndrome and erythema nodosum: the simultaneous occurrence of 2 reactive
      dermatoses.
AB  - BACKGROUND: The simultaneous occurrence of Sweet's syndrome (SS) and erythema
      nodosum (EN) in 1 patient is rare. Our review of the literature revealed only 11
      biopsy-proved cases in which the 2 reactive dermatoses occurred together. None
      were associated with an underlying malignant neoplasm. OBSERVATIONS: We report a
      biopsy-proved case of SS and EN occurring simultaneously in a patient with an
      underlying malignant neoplasm (specifically, acute myelogenous leukemia). We also
      report another biopsy-proved case of SS and EN occurring simultaneously in a
      patient with underlying Crohn's disease. CONCLUSIONS: The simultaneous occurrence
      of SS and EN in 1 patient is rarely reported. Both disorders are reactive
      dermatoses that share many overlapping features. Although individually
      distinctive, SS and EN are also part of a growing continuum of reactive
      dermatoses. Our expanded understanding of the similarities and simultaneous
      manifestation of SS and EN may help us in the future to identify a common
      underlying mechanism of pathogenesis.

PMID- 9923784
TI  - Allergic contact and photoallergic contact dermatitis to plant and pesticide
      allergens.
AB  - BACKGROUND: The panel of patch test allergens used for the evaluation of patients
      with suspected photoallergy typically does not include plant and pesticide
      allergens. The prevalence of allergic contact dermatitis and photoallergic
      contact dermatitis to plant and pesticide allergens was determined for this
      subgroup of patients. OBSERVATION: Positive reactions were detected in 12 of 26
      patients who were tested with our photoallergen series: 5 with allergic contact
      dermatitis, 5 with photoallergic contact dermatitis, and 2 with both. Four of the
      12 patients had positive patch and photo-patch test reactions to plant allergens,
      pesticide allergens, or both. The positive patch test reactions were to the
      plants Taraxacum officinale (dandelion) and Tanacetum vulgare (tansy) and to the
      pesticides folpet and captafol. Positive photo-patch test reactions were to the
      pesticides folpet and captan. The histories of the patients suggested that 2 or 3
      of the 4 patients had clinically relevant reactions. In the other 8 patients,
      positive reactions to the patch and photo-patch tests included fragrances,
      sunscreens, and antibacterial agents. CONCLUSION: Plant and pesticide allergens
      should be included in the patch and photo-patch test series used for the
      evaluation of patients with suspected photoallergy.

PMID- 9923785
TI  - The new herpesviruses: emerging pathogens of dermatological interest.
AB  - OBJECTIVES: To discuss the current knowledge of 3 recently discovered human
      herpesviruses (HHV-6, HHV-7, and HHV-8), and to provide a dermatological point of
      view. DATA SOURCES: References identified from bibliographies of pertinent
      articles in the English language. STUDY SELECTION AND DATA EXTRACTION: Articles
      were selected according to their impact factor and the interest for
      dermatologists. DATA SYNTHESIS: As the other members of the family Herpesviridae,
      HHV-6, HHV-7, and HHV-8 may cause a primary infection, establish latent infection
      in a specific set of cells of their host, and then reactivate if conditions of
      altered immunity develop. The main pathological conditions associated with them
      are discussed. CONCLUSIONS: Human herpesvirus 6, HHV-7, and HHV-8 have provided
      new insights in some dermatological diseases. Although new studies are needed,
      they may have a profound impact on dermatology in the years to come.

PMID- 9923786
TI  - Therapy of pemphigus vulgaris.

PMID- 9923787
TI  - Use of topical products for maintaining remission in rosacea.

PMID- 9923788
TI  - Pathogenesis of exercise-induced urticarial vasculitis lesions: can the changes
      be extrapolated to all leukocytoclastic vasculitis lesions?

PMID- 9923789
TI  - Prednisone is more effective than prednisolone metasulfobenzoate in the treatment
      of bullous pemphigoid.

PMID- 9923790
TI  - Butyl nitrite-induced acrocyanosis in an HIV-infected patient.

PMID- 9923791
TI  - Satoyoshi syndrome.

PMID- 9923792
TI  - Topical tetracycline treatment of erosive oral lichen planus.

PMID- 9923793
TI  - Acute generalized exanthematous pustulosis induced by metronidazole: the role of
      patch testing.

PMID- 9923794
TI  - Growth hormone, alone and in combination with insulin, increases whole body and
      skeletal muscle protein kinetics in cancer patients after surgery.
AB  - OBJECTIVE: To investigate the impact of growth hormone, alone and in combination
      with insulin, on the protein kinetics of patients with upper gastrointestinal
      (GI) tract cancer who have undergone surgery and are receiving total parenteral
      nutrition (TPN). SUMMARY BACKGROUND DATA: Patients with malignancies of the upper
      GI tract are at increased risk for malnutrition and perioperative death and
      complications. Standard nutritional support has not significantly altered
      outcome. Growth hormone (GH) and insulin have been shown to have some benefit in
      patients with cancer; however, their action in patients undergoing resection has
      not previously been studied. METHODS: Thirty patients undergoing surgery for
      upper GI tract malignancies were prospectively randomized into one of three
      nutritional support groups after surgery: 10 patients received standard TPN, 10
      received TPN plus daily injections of GH, and 10 received daily GH, systemic
      insulin, and TPN. The patients underwent a protein kinetic radiotracer study on
      the fifth day after surgery to determine whole body and skeletal muscle protein
      kinetics. RESULTS: Patients who received standard TPN only were in a state of
      negative skeletal muscle protein net balance. Those who received GH and insulin
      had improved skeletal muscle protein net balance compared with the TPN only
      group. Whole body protein net balance was improved in the GH and the GH and
      insulin groups compared with the TPN only group. GH and insulin combined did not
      improve whole body net balance more than GH alone. GH administration
      significantly increased serum IGF-1 and GH levels. Insulin infusion significantly
      increased serum insulin levels and the insulin/glucagon ratio. CONCLUSION: Growth
      hormone and GH plus insulin regimens improve protein kinetic parameters in
      patients with upper GI tract cancer who are receiving TPN after undergoing
      surgery.

PMID- 9923796
TI  - The evolution of surgical nutrition: nutrient and anabolic interventions.

PMID- 9923795
TI  - A submaximal dose of insulin promotes net skeletal muscle protein synthesis in
      patients with severe burns.
AB  - OBJECTIVE: To investigate the hypothesis that a submaximal insulin dose reverses
      the net muscle catabolism associated with severe burns, and to determine its
      effects on amino acid kinetics. SUMMARY BACKGROUND DATA: The authors previously
      showed that a maximal dose of insulin administered to patients with severe burns
      promoted skeletal muscle glucose uptake and net protein synthesis. However, this
      treatment was associated with caloric overload resulting from the large
      quantities of exogenous glucose required to maintain euglycemia, and hypoglycemia
      was a potential problem. METHODS: Thirteen patients were studied after severe
      burn injury (>60% total body surface area). Patients were randomly treated by
      standard care (n = 5) or with exogenous insulin (n = 8). Data were derived from
      an arteriovenous model with primed-continuous infusions of stable isotopes and
      biopsies of the vastus lateralis muscle. RESULTS: Net amino acid balance was
      significantly improved with insulin treatment. Skeletal muscle protein synthesis
      was significantly greater in the group receiving insulin, whereas muscle protein
      breakdown was not different between the groups. This submaximal dose of insulin
      did not affect glucose or amino acid uptake or require a greater caloric intake
      to avoid hypoglycemia. CONCLUSIONS: Submaximal insulin can promote muscle
      anabolism without eliciting a hypoglycemic response.

PMID- 9923798
TI  - Stented versus nonstented pancreaticojejunostomy after pancreatoduodenectomy: a
      prospective study.
AB  - OBJECTIVE: To compare morbidity and mortality rates of stented versus nonstented
      pancreaticojejunostomy after partial pancreatoduodenectomy. BACKGROUND DATA:
      Despite a marked reduction in the mortality rate after partial
      pancreatoduodenectomy in recent years, leakage of the pancreaticojejunostomy
      still occurs in 5% to 25% of patients and remains the major source of
      complications. METHODS: The authors compared the morbidity and mortality rates of
      85 consecutive patients who had a partial pancreatoduodenectomy with (n = 44) or
      without (n = 41) temporary stented external drainage of the pancreatic duct
      between 1994 and 1997. RESULTS: A pancreatic fistula was diagnosed in 3 of the 44
      patients (6.8%) with stents versus 12 of the 41 patients (29.3%) without stents.
      Surgical reintervention was necessary in 1 of the 3 patients with a pancreatic
      fistula in the stented group and 3 of the 12 patients with a pancreatic fistula
      in the nonstented group. There were two deaths after surgery, both in the
      nonstented group. The median hospital stay after surgery was 13 days in patients
      with stents and 29 days in patients without stents. CONCLUSION: In this
      nonrandomized prospective observational study, temporary external drainage of the
      pancreatic duct with a PVC tube significantly reduced the leakage rate of the
      pancreaticojejunostomy as well as the duration of hospital stay after partial
      pancreatoduodenectomy. Although promising, these observations require
      confirmation by further studies.

PMID- 9923799
TI  - Quality of life after laparoscopy-assisted Billroth I gastrectomy.
AB  - OBJECTIVE: To evaluate the quality of life of patients who had undergone
      laparoscopy-assisted Billroth I gastrectomy (LAG) for cure of cancer. SUMMARY
      BACKGROUND DATA: In 1994, the authors reported the first case of LAG for early
      gastric cancer, and this approach quickly has been adopted by Japanese surgeons.
      However, little is known about the subjective clinical results of this less
      invasive surgery. METHODS: Quality of life was estimated using the 24-item
      questionnaire with a scoring system of 1, 2, and 3 and was compared between 41
      consecutive patients with LAG and 35 with conventional open gastrectomy. All
      patients underwent Billroth I gastrectomy for early gastric cancer from January
      1993 to July 1997 and were alive without recurrence. RESULTS: Patients who had
      undergone LAG were taking a normal diet (100%) with >66% of volume at each meal
      (90%), showed no decreased performance status (90%), and were satisfied with
      their surgical results (88%). Patients with LAG, when compared with open
      gastrectomy, showed significantly better results with regard to weight loss,
      difficulty in swallowing, heartburn and belch, early dumping syndrome, and total
      score. LAG was better accepted by the patients. CONCLUSIONS: Quality of life
      after Billroth I gastrectomy was significantly better in patients in whom a
      laparoscopic technique was used than in those who underwent a conventional
      method. LAG is less invasive and better accepted by patients and is the procedure
      of choice for the treatment of early gastric cancer.

PMID- 9923800
TI  - Computerized nuclear morphometry: a new morphologic assessment for advanced
      gastric adenocarcinoma.
AB  - OBJECTIVE: To evaluate the correlation between the morphologic nuclear features
      and clinicopathologic parameters in patients with advanced gastric cancer.
      SUMMARY BACKGROUND DATA: Nuclear profiles have been reported as useful prognostic
      predictors in various cancers. Data from computerized morphometries are objective
      and quickly derived using conventional microscopic analysis. However, this image
      analysis of nuclear features has rarely been applied to investigations of gastric
      adenocarcinoma. Moreover, it remains to be shown what types of biologic factors
      influence the nuclear features. METHODS: Morphometric nuclear features (nuclear
      area, perimeter, and shape) were analyzed in 202 patients with serosal-invaded
      gastric cancer (stage II and III) who underwent curative gastrectomy. In each
      case, 300 cancer nuclei were analyzed on routine hematoxylin and eosin-stained
      slides through the use of a computer-assisted image analysis system by tracing
      the nuclear profiles (magnification x400) on a computer monitor. The morphometric
      data were compared with patient survival, clinicopathologic status, DNA ploidy
      pattern of tumors, expression of p53 protein, and proliferative activity of
      cancer cells. RESULTS: Lymph node metastasis, lymphatic invasion, and venous
      invasion were more frequently detected in patients with large nuclear areas.
      Significant correlations were detected between the size of the nuclear area of
      cancer cells and the biologic factors of tumors, such as expression of p53, Ki-67
      labeling index, and DNA ploidy pattern. The 5-year survival rate of the 100
      patients in the large-nuclear group (nuclear area >45.3 microm2) was 47.6% and
      was significantly lower than the 74.4% rate of the 98 patients in the small
      nuclear group (nuclear area < or =45.3 microm2). Moreover, the nuclear area was
      found to be an independent prognostic factor in the multivariate analysis.
      CONCLUSIONS: Gastric cancer cells with a large nuclear area express mutated p53
      protein and have high proliferative activity. Moreover, such cancer cells have
      high potential for invasion to the microvessels in the gastric wall. Thus,
      nuclear morphometry is a new and useful morphologic predictor for metastatic
      potential in advanced gastric cancer.

PMID- 9923797
TI  - Murine mentors: transgenic and knockout models of surgical disease.
AB  - OBJECTIVE: Transgenic and knockout technologies have emerged from the "molecular
      biology revolution" as unprecedented techniques for manipulating gene function in
      intact mice. The goals of this review are to outline the techniques of creating
      transgenic and knockout mice, and to demonstrate their use in elucidation of the
      molecular mechanisms underlying common surgical diseases. SUMMARY BACKGROUND
      DATA: Gain of gene function is created by transgenic technology, whereas gene
      function is ablated using gene knockouts. Each technique has distinctive
      applications and drawbacks. A unique feature of genetically manipulated mice is
      that combinatorial genetic experiments can be executed that precisely define the
      functional contribution of a gene to disease progression. Transgenic and knockout
      mouse models of wound healing, cardiovascular disease, transplant immunology, gut
      motility and inflammatory bowel disease, and oncology are beginning to illuminate
      the precise molecular regulation of these diseases. Transgenic technology has
      also been extended to larger mammals such as pigs, with the goal of using genetic
      manipulation of the xenogenic immune response to increase the availability of
      transplant organs. Continual refinements in gene manipulation technology in mice
      offer the opportunity to turn genes on or off at precise time intervals and in
      particular tissues, according to the needs of the investigator. Ultimately,
      investigation of disease development and progression in genetically manipulated
      mammals may delineate new molecular targets for drug discovery and provide novel
      platforms for drug efficacy screens. CONCLUSIONS: Emulation of human disease and
      therapy using genetically manipulated mammals fulfills a promise of molecular
      medicine: fusion of molecular biochemistry with "classical" biology and
      physiology. Surgeons have unique skills spanning both worlds that can facilitate
      their success in this expanding arena.

PMID- 9923801
TI  - Assessment of cervical lymph node metastasis in esophageal carcinoma using
      ultrasonography.
AB  - OBJECTIVE: To evaluate the efficacy of ultrasonography for the diagnosis of
      cervical lymph node metastasis in esophageal carcinoma. SUMMARY BACKGROUND DATA:
      Ultrasound (US) examination is useful for diagnosing lymph node metastasis.
      However, few reports have examined its role in the decision to perform cervical
      lymph node dissection in esophageal carcinoma. METHODS: Ultrasound examination
      was performed to evaluate cervical lymph node metastasis in 519 patients with
      esophageal carcinoma. The patients were divided into 5 groups according to
      treatment received: group 1, 153 patients who underwent curative resection of
      primary tumor by right thoracotomy and complete bilateral cervical
      lymphadenectomy; group 2, 112 patients who underwent curative resection of
      primary tumor by right thoracotomy but without cervical lymphadenectomy; group 3,
      78 patients who underwent esophagectomy by left thoracotomy or blunt dissection
      with or without removal of cervical lymph nodes; group 4, 76 patients with
      palliative resection without cervical lymphadenectomy; and group 5, 100 patients
      without any surgical treatment. US diagnosis was compared with histologic
      findings or cervical lymph node recurrence. RESULTS: Lymph node metastasis was
      detected in 30.8% of patients (160/519). The sensitivity, specificity, and
      accuracy of US diagnosis in group 1 were 74.5%, 94.1%, and 87.6%, respectively.
      Cervical lymph node recurrence was seen in 7 patients (4.6%) in group 1, in 4
      patients (3.6%) in group 2, and 3 patients (3.8%) in group 3. Although the
      incidence of cervical lymph node metastasis as determined by US examination was
      high in groups 4 and 5, almost none of the patients died of cervical lymph node
      metastasis. CONCLUSIONS: Ultrasound examination plays a useful role in the
      decision to perform cervical lymph node dissection in patients with esophageal
      carcinoma, particularly in those with potentially curative dissection.

PMID- 9923802
TI  - Transforming growth factor-betas and their signaling receptors are coexpressed in
      Crohn's disease.
AB  - OBJECTIVE: To evaluate mechanisms that contribute to tissue repair and tissue
      remodeling in Crohn's disease (CD). SUMMARY BACKGROUND DATA: Transforming growth
      factor-betas (TGF-betas) are involved in different chronic inflammatory
      disorders. They function by binding to two receptors, type I (TbetaR-I) subtype
      ALK5 and type II (TbetaR-II), which are concomitantly required for signal
      transduction. METHODS: Tissues were obtained from 18 patients with CD (10 female
      patients, 8 male patients, median age 38.7 years [range 16 to 58 years])
      undergoing surgery because of CD-related complications. Tissue samples of 18
      healthy organ donors (10 female subjects, 8 male subjects, median age 50.3 years
      [range 15 to 65 years]) served as controls. The expression and localization of
      TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-IALK5, TbetaR-II, and TbetaR-III were
      studied by Northern blot analysis, in situ hybridization, and
      immunohistochemistry. RESULTS: On Northern blot analysis, 94% of the CD samples
      exhibited enhanced TGF-beta1, TGF-beta3, and TbetaR-II mRNA expression compared
      with controls. TGF-beta2 was increased in 72%, TbetaR-IALK5 in 72%, and TbetaR
      III in 82% of the patients with CD. On in situ hybridization and
      immunohistochemical analysis, TGF-beta1, TbetaR-IALK5, and TbetaR-II were seen to
      be colocalized in the lamina propria cells and in the lymphocytes closest to the
      luminal surface, but also in the remaining epithelial cells, and in fibroblasts
      of CD tissue samples. CONCLUSIONS: The concomitant overexpression of TGF-betas
      and their signaling receptors in CD points to a potential role of these
      regulatory molecules in the pathophysiology of CD. Activation of TGF-beta
      mediated pathways might promote the repair of mucosal injury by enhancing the
      process of reepithelization, but might also contribute to extracellular matrix
      generation and subsequently to intramural fibrosis and intestinal obstruction.

PMID- 9923803
TI  - Role of nodal involvement and the periductal soft-tissue margin in middle and
      distal bile duct cancer.
AB  - OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct
      cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA:
      Lymph node involvement and neural plexus invasion are the prognostic factors most
      amenable to surgery in Bm and Bi disease. However, a detailed analysis of these
      factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease
      (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise
      determination was made of lymph node involvement and neural plexus invasion.
      Important prognostic factors were examined by clinicopathologic study to apply
      these findings to surgical management. RESULTS: Frequencies of nodal involvement
      for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and
      superior pancreaticoduodenal lymph nodes were most commonly involved. Neural
      plexus invasion occurred in 20% of patients, particularly involving the plexus in
      the hepatoduodenal ligament and pancreatic head. Tumor was present at the
      surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively.
      Five-year survival rates were 65% in the absence of nodal metastasis and 21% with
      nodal metastasis. A significant correlation existed between absence of tumor at
      the surgical margin and survival. A Cox proportional hazard model projected
      absence of tumor at the surgical margin, followed by nodal involvement, as the
      strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical
      margin and nodal involvement are important independent prognostic factors in Bm
      and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal
      vein resection, is necessary for patients with Bm disease, and a wide nodal
      dissection is essential in all patients.

PMID- 9923804
TI  - Prognostic factors after hepatic resection for hepatocellular carcinoma
      associated with Child-Turcotte class B and C cirrhosis.
AB  - OBJECTIVE: To evaluate prognostic factors after resection of hepatocellular
      carcinoma (HCC) in patients with Child-Turcotte class B and C cirrhosis. SUMMARY
      BACKGROUND DATA: Although hepatic resection remains the mainstay in the treatment
      of HCC and can be performed with low morbidity and mortality rates in patients
      without cirrhosis, its role is poorly defined for patients with severe cirrhosis.
      METHODS: From 1986 to 1996, partial hepatectomy was performed for HCC in 63
      patients with Child-Turcotte class B (n = 46) and C (n = 17) cirrhosis. There
      were 46 men and 17 women, with an average age of 61.2 years (range 35 to 79
      years). Associated conditions were diabetes mellitus in 45, esophageal varices in
      32, severe hypersplenism in 26, cholelithiasis in 13, gastroduodenal ulcer in 6,
      and hiatal hernia, gastric lymphoma, splenic abscess, and pancreatic cyst each in
      1. Concomitant surgical procedures were performed for most of these conditions.
      RESULTS: Major complications occurred in 17 patients (27%), six (9.5%) of whom
      died within 1 month after surgery. The overall in-hospital death rate was 14.3%.
      Liver failure and intraabdominal sepsis were mostly fatal complications. The
      overall and disease-free survival rates, respectively, were 70.2% and 64.5% at 1
      year, 43.5% and 23.8% at 3 years, and 21.4% and 14.9% at 5 years. Multivariate
      analysis with the Cox regression model revealed that favorable factors for
      survival were Child class B, no transcatheter arterial embolization before
      surgery, young age, and low alanine aminotransferase (ALT) level before surgery.
      CONCLUSIONS: Hepatic resection can provide a favorable result in young patients
      with HCC complicating Child class B cirrhosis with low hepatitis activity, but
      transcatheter arterial embolization before surgery should be avoided in such
      patients.

PMID- 9923805
TI  - Delay in diagnosis of breast cancer.
AB  - OBJECTIVES: To assess the consequences of physician delay in the diagnosis of
      breast cancer by comparing stage, treatment, and outcome of patients with and
      without delay, and to identify patient characteristics that may make diagnosis
      more difficult. SUMMARY BACKGROUND INFORMATION: Delay in diagnosis of breast
      cancer is the most common clinical scenario resulting in malpractice litigation.
      METHODS: The records of 1014 patients were reviewed and the events preceding the
      diagnosis were reconstructed. Accurate assessment of the physician delay in
      diagnosis could be made for 606 patients, 51 (8%) with physician delay >3 months.
      Patients with delay were comparable to patients without delay in terms of age,
      height, weight, age at menarche, pregnancies, children, proportion in menopause,
      age at menopause, and family history of breast cancer. RESULTS: Thirty-six
      percent of patients who had a delay in diagnosis had normal mammograms versus 7%
      of patients without delay. Cancers in patients with delay were significantly
      larger on average than in those without delay, but there were no significant
      differences in pathology, differentiation, nodal status, TNM stage, treatment, or
      outcome. CONCLUSIONS: Physician delay in the diagnosis of breast cancer is
      common, and patients with delay are similar to patients without delay, although
      they are more likely to have normal mammograms. The consequences of physician
      delay in terms of stage at diagnosis, treatment, and outcome were not
      statistically significant.

PMID- 9923806
TI  - Surgical management of Merkel cell carcinoma.
AB  - OBJECTIVES: To characterize the natural history of Merkel cell carcinoma (MCC)
      and to analyze the influence of patient, tumor, and treatment-related variables
      on survival and recurrence. SUMMARY BACKGROUND DATA: Approximately 425 cases of
      MCC have been described in the literature. This study represents the largest
      experience reported. METHODS: A review was performed of patients who had been
      treated at Memorial Sloan-Kettering Cancer Center for MCC between 1969 and 1996.
      Follow-up data were available for 102 of the 109 (94%) patients identified.
      RESULTS: The overall 5-year disease-specific survival rate was 74%. The median
      follow-up was 35 months. For all patients, the only independent predictor of
      survival was the tumor stage at presentation. For patients with stage I disease,
      the tumor size at presentation was also an independent predictor of survival.
      Recurrence of disease occurred in 55 patients (55%), and the most common site of
      first recurrence was within the draining lymph nodes (n = 35). Elective lymph
      node dissection was the only parameter independently predictive of improved
      relapse-free survival. The overall disease-specific survival rate after
      recurrence was 62%. Predictors of improved disease-specific survival after
      recurrence included nodal as compared to local or distant recurrence, the ability
      to render the patient free of disease after recurrence, and a disease-free
      interval of >8 months. CONCLUSION: The prognosis for patients with MCC is
      favorable, and even after recurrence the majority of patients experience long
      term survival. Incorporation of size into the staging system more accurately
      predicts survival in patients with stage I disease. Although elective lymph node
      dissection decreased the rate of recurrence, it was not associated with improved
      overall survival.

PMID- 9923807
TI  - Posttranslational modifications of cardiac and skeletal muscle proteins by
      reactive oxygen species after burn injury in the rat.
AB  - OBJECTIVE: To determine the involvement of oxidative damage in muscle wasting
      after burn injury. SUMMARY BACKGROUND DATA: Burn injury damages tissue at the
      site of the burn and also affects peripheral tissue. There is evidence to suggest
      that reactive oxygen species may be generated in increased amounts after burn,
      and these may contribute to wound healing and to posttranslational modifications
      of tissue constituents distant from the wound site. METHODS: The oxidation of
      muscle proteins was assessed, using the dinitrophenylhydrazine assay for carbonyl
      content, in muscles of rats after a full-thickness skin scald burn covering 20%
      of the total body surface area, over a 6-week period. In this model, rats failed
      to incur normal body weight or muscle weight gain. RESULTS: Soleus, extensor
      digitorum longus, diaphragm, and heart ventricle proteins were oxidatively
      damaged after injury. The extent of tissue protein oxidation, however, differed
      depending on the time points studied. In general, higher levels of protein
      carbonyl group formation, an indicator of oxidative damage, were found to occur
      within 1 to 5 days after injury, and the oxidized protein content of the various
      tissues decreased during the later stages. Both sarcoplasmic and myofibrillar
      carbonyl-containing proteins accumulated in diaphragm 3 days after burn injury
      and were rapidly removed from the tissue during a 2-hour in vitro incubation.
      This coincided with increased proteolytic activity in diaphragm. CONCLUSIONS:
      These observations suggest that the loss of proteins modified by reactive oxygen
      species may contribute to the burn-induced protein wasting in respiratory and
      other muscles by a proteolytically driven mechanism.

PMID- 9923809
TI  - Disseminated intravascular coagulation and sustained systemic inflammatory
      response syndrome predict organ dysfunctions after trauma: application of
      clinical decision analysis.
AB  - OBJECTIVE: To determine the accuracy of disseminated intravascular coagulation
      (DIC) and sustained systemic inflammatory response syndrome (SIRS) in predicting
      posttrauma multiple organ dysfunction syndrome (MODS) and to find a simple
      laboratory test for detecting MODS. SUMMARY AND BACKGROUND DATA: In trauma
      patients, the duration of SIRS is the main determinant for MODS and outcome.
      METHODS: One hundred thirty-six patients with trauma were classified into
      subgroups according to the duration of SIRS: patients without SIRS (n = 27),
      patients with SIRS for <2 days (n = 52), and patients with SIRS for > or =3 days
      (n = 57). Platelets and five coagulation and fibrinolytic laboratory tests for
      diagnosing DIC were measured on the day of admission and on days 1 through 4
      after admission. Simultaneously, the DIC score was determined. The diagnostic
      accuracy of DIC and sustained SIRS for the prediction of MODS was determined
      using likelihood ratios. A receiver operating characteristic curve of platelet
      counts for predicting MODS was also constructed. RESULTS: Platelet counts showed
      significant differences among the three groups. The incidence of DIC, acute
      respiratory distress syndrome, and MODS was significantly higher in patients with
      SIRS for > or =3 days compared with those in the other groups, and they had a
      poor outcome. Likelihood ratios of DIC and SIRS for > or =3 days for predicting
      posttrauma MODS were 11.6 and 6.25, respectively. Platelet counts (80 x 10(9)/l)
      on day 1 had a sensitivity of 83.3% and a specificity of 100% for predicting
      MODS. CONCLUSIONS: Disseminated intravascular coagulation and sustained SIRS are
      strong determinants for posttrauma MODS. This retrospective analysis supports the
      possibility that platelet counts can be used as a simple laboratory test for
      predicting MODS. This hypothesis requires proof using a prospective clinical
      survey.

PMID- 9923808
TI  - Effect of topical local anesthetic application to skin harvest sites for pain
      management in burn patients undergoing skin-grafting procedures.
AB  - OBJECTIVE: To determine if topical administration of local anesthesia, applied to
      fresh skin-harvest sites, reduces pain and analgesic requirements after surgery.
      SUMMARY BACKGROUND DATA: Nonopioid treatments for pain after therapeutic
      procedures on patients with burns have become popular because of the side effects
      associated with narcotics. The topical administration of local anesthesia
      originally offered little advantage because of poor epidermal penetration.
      METHODS: This study compares 2% lidocaine with 0.5% bupivacaine or saline,
      topically applied after skin harvest, to determine what effect this may have on
      pain and narcotic use. Sixty patients with partial- or full-thickness burns to
      approximately 10% to 15% of their body were randomly divided into three groups:
      group 1 received normal saline, group 2 had 0.5% bupivacaine, and group 3 had 2%
      lidocaine sprayed onto areas immediately after skin harvest. Blood samples were
      subsequently obtained to measure concentrations of the local anesthetic.
      Hemodynamic variables after surgery, wake-up times, emetic symptoms, pain, and
      narcotic use were compared. RESULTS: Higher heart rates were noted in the placebo
      group than in those receiving lidocaine or bupivacaine. No differences were noted
      in recovery from anesthesia or emetic symptoms. Pain scores were lower and 24
      hour narcotic use was less in patients who received lidocaine. Plasma lidocaine
      levels were greater than bupivacaine at all time points measured. CONCLUSIONS:
      Topical lidocaine applied to skin-harvest sites produced an analgesic effect that
      reduced narcotic requirements compared with patients who received bupivacaine or
      placebo. Local anesthetic solutions aerosolized onto skin-harvest sites did not
      affect healing or produce toxic blood concentrations.

PMID- 9923811
TI  - Reconstructive surgery for ischemic-type lesions at the bile duct bifurcation
      after liver transplantation.
AB  - OBJECTIVE: To assess the feasibility, morbidity, mortality, and clinical success
      rate of surgical reconstruction of the biliary system in patients with ischemic
      type biliary lesions in their liver graft. SUMMARY BACKGROUND DATA: After liver
      transplantation, strictures in the biliary tree with secondary sludge formation
      can occur in the absence of vascular problems. Jaundice, pruritus, and recurrent
      cholangitis are predominant clinical features leading to considerable morbidity.
      Interventional measures are the first-line treatment but are frequently only of
      transient success. Retransplantation is usually considered when interventional
      treatment is not effective. METHODS: Surgical exploration and reconstruction was
      performed in 17 patients with ischemic-type biliary strictures at a median of 2
      years after liver transplantation. Findings during surgery, surgical strategies,
      and postsurgical courses are described. Clinical symptoms and biochemical
      parameters of cholestasis and liver function were analyzed in the postsurgical
      course. RESULTS: During surgery, all 17 patients were found to have strictures or
      sclerotic changes involving the hepatic bifurcation and extrahepatic bile duct.
      Sludge or stones were present in nine patients. In 14 patients with viable bile
      ducts proximal to the bifurcation, surgical reconstruction was performed by
      resection of the bifurcation and hepaticojejunostomy. In three patients with more
      extensive biliary destruction, portoenterostomy with or without peripheral
      hepatojejunostomy was performed. The prevalence rate of biliary infection at
      surgery was 93%; the predominant organisms were Candida and enterococci. The
      perioperative mortality rate was 0%. Clinical symptoms and biochemical parameters
      became normal or were considerably improved in 14 of 16 patients (88%).
      CONCLUSIONS: The hepatic bifurcation seems to be a predominant site for ischemic
      type biliary changes after liver transplantation. Surgical treatment by resection
      of the bifurcation and reconstruction by high hepaticojejunostomy is a safe and
      highly effective approach leading to cure or persistent major improvement in most
      patients.

PMID- 9923810
TI  - Thoracic duct in patients with multiple organ failure: no major route of
      bacterial translocation.
AB  - OBJECTIVE: To determine whether translocation of bacteria or endotoxin occurred
      into the thoracic duct in patients with multiple organ failure (MOF). SUMMARY
      BACKGROUND DATA: Translocation of bacteria or endotoxin has been proposed as a
      causative factor for MOF in patients without an infectious focus, although it has
      rarely been demonstrated in patients at risk for MOF. Most studies have
      investigated the hematogenic route of translocation, but it has been argued that
      lymphatic translocation of bacteria or endotoxin by the thoracic duct is the
      major route of translocation. METHODS: The thoracic duct was drained for 5 days
      in patients with MOF caused either by generalized fecal peritonitis (n = 4) or by
      an event without clinical and microbiologic evidence of infection (n = 4).
      Patients without MOF who were undergoing a transthoracic esophageal resection
      served as controls. In lymph and blood, concentrations of endotoxin,
      proinflammatory cytokines, and antiinflammatory cytokines were measured. RESULTS:
      Endotoxin concentrations in lymph and blood of patients with MOF ranged from 39
      to 63 units per liter and were not significantly different from concentrations in
      patients without MOF. The quantity of endotoxin transported by the thoracic duct
      in the study group was small. In patients with MOF, low levels of proinflammatory
      cytokines and high levels of antagonists of these cytokines were found.
      CONCLUSION: This study provides evidence that translocation (especially of
      endotoxin) occurs into the thoracic duct. However, these data do not support the
      concept that the thoracic duct is a major route of bacterial translocation in
      patients with MOF.

PMID- 9923812
TI  - Outcome of femoropopliteal angioplasty.
AB  - OBJECTIVE: To assess prospectively the outcome of femoropopliteal angioplasty and
      investigate prognostic indicators of success. BACKGROUND: Percutaneous
      transluminal angioplasty is commonly used to treat symptomatic femoropopliteal
      stenoses or occlusions, but the durability of the procedure is uncertain.
      METHODS: Seventy-four consecutive patients treated by femoropopliteal angioplasty
      for intermittent claudication (43), rest pain (4), and tissue loss (27) were
      followed by assessment of symptoms, ankle-brachial pressure index (ABPI) to
      measure hemodynamic outcome, and duplex monitoring of velocity gradient at the
      angioplasty site to identify restenosis at 1 day and 3, 6, 9, and 12 months.
      Univariate comparisons, life table analysis, and backward stepwise regression
      were used to investigate factors predicting the symptomatic and hemodynamic
      outcome and restenosis. RESULTS: Technical success was obtained in 67 patients
      (91%); failure occurred in 7 patients. At 1 year, a successful symptomatic
      outcome was achieved in 35 patients (51%), hemodynamic success was achieved in 41
      patients (58%), and restenosis developed in 39%. ABPI at 24 hours after
      angioplasty was the most significant variable predicting a symptomatic outcome,
      hemodynamic outcome, and restenosis at 12 months. Life table analysis
      demonstrated that in 24% of patients with a 24-hour ABPI > or =0.9, restenosis
      developed by 12 months, compared with 64% of patients with a 24-hour ABPI <0.9.
      CONCLUSION: Only half of the patients treated by femoropopliteal angioplasty had
      symptomatic improvement at 1 year, raising concern about the cost-benefit ratio
      of this procedure. Restoration of ABPI to >0.9 predicted a favorable outcome.

PMID- 9923813
TI  - Angiographic 20-year follow-up of 61 consecutive patients with internal thoracic
      artery grafts.
AB  - OBJECTIVE: To assess the behavior of internal thoracic artery (ITA) grafts versus
      venous grafts in repeated angiograms up to 20 years. SUMMARY BACKGROUND DATA: Use
      of ITA grafts to bypass left anterior descending artery stenosis has been shown
      to be associated with improved survival in patients undergoing coronary artery
      bypass grafting. METHODS: Sixty-one consecutive patients who received one or two
      ITA grafts and who underwent surgery from Oct. 5, 1971, to Dec. 18, 1973, in
      Helsinki University Central Hospital, Finland, were included in this prospective
      follow-up series. Fifty-six of the patients (92%) also received at least one
      venous graft. The number of distal anastomoses was 157, of which 47.7% (75) were
      performed with ITA grafts. The median age of the patients was 47.7 years (range
      30.0 to 63.1), and 85% (52) were men. RESULTS: After 20 years of follow-up, 18/20
      (90%) of the survivors underwent angiography; the patency rate was 88.9% for ITA
      grafts and 47.8% for venous grafts. Cumulative graft patency at 20 years, using
      all the information obtained from repeated angiographic examinations and
      autopsies, was also calculated to eliminate selection bias. The cumulative 20
      year patency rate was 81% for ITA-left anterior descending artery anastomoses,
      53.8% for venous graft-right coronary artery anastomoses, and 48.5% for venous
      graft-left circumflex artery anastomoses. In paired comparisons between
      anastomoses, the patency time of the ITA-left anterior descending artery
      anastomoses was on average 2.8 years longer than the venous graft-left circumflex
      artery patency time and 2.6 years longer than the venous graft-right coronary
      artery. CONCLUSIONS: Internal thoracic artery grafts, especially in left anterior
      descending artery anastomoses, should be considered as a primary solution in
      coronary artery bypass grafting surgery in patients with >10 years of life
      expectancy; if venous grafting is preferred, further evidence is needed.

PMID- 9923814
TI  - A new orally active antitumor 1R,2R-cyclohexanediamine-platinum(IV) complex:
      trans-(n-valerato)chloro(1R,2R-cyclohexanediamine) (oxalato)platinum(IV).
AB  - PURPOSE: The authors have previously reported that trans-bis(n-valerato)(1R,2R
      cyclohexanediamine) (oxalato)platinum(IV) (C5-OHP), an oxaliplatin derivative, is
      an orally active antitumor agent in an intraperitoneal (i.p.) L1210 murine
      leukemia model. In this study, several oxaliplatin derivatives of the general
      formula trans-(carboxylato)chloro(1R,2R-cyclohexanediamine)(oxala to)platinum(IV)
      were synthesized in order to find new derivatives with greater oral activity than
      C5-OHP in a clinically predictive tumor model. In the formula, the carboxylate
      and chloride ligands are situated in axial positions. METHOD: Four complexes with
      the axial carboxylate ligands n-butyrate, n-valerate, n-caproate or n-heptanoate
      were synthesized and designated C4-OHP-Cl, C5-OHP-Cl, C6-OHP-Cl and C7-OHP-Cl,
      respectively. The oral antitumor activity of the complexes was evaluated against
      the murine reticulosarcoma M5076 implanted subcutaneoulsy (s.c.) in to male BDF1
      mice. The complexes were administered orally daily for 5 days in two cycles
      initiated on days 5 and 12 postimplantation. The physicochemical properties were
      examined by measuring the concentrations of the complexes in test solutions at
      intervals by HPLC. The pharmacokinetic behaviors of C5-OHP-Cl, C6-OHP-Cl and C5
      OHP following a single oral administration were studied in non-tumor-bearing male
      BDFl mice. RESULTS: Of the complexes synthesized in this study, C5-OHP-Cl, which
      exhibited high activity in the i.p. L1210 model, was found to be orally active in
      the s.c. M5076 model while C5-OHP was not. The in vitro reduction of the
      complexes by ascorbate was much more rapid than that of C5-OHP, while the
      complexes were more stable than C5-OHP in HCl-acidic and alkaline solutions.
      Pharmacokinetic study showed that Cmax and AUC0 24h values of plasma total and
      filterable platinum of C5-OHP-Cl were four to six times greater than those of C5
      OHP, indicating that C5-OHP-Cl was absorbed more than C5-OHP. CONCLUSION: C5-OHP
      Cl was found to be a superior 1-OHP derivative C5-OHP, exhibiting significant
      oral antitumor activity in the s.c. M5076 model. The enhanced activity of C5-OHP
      Cl was considered to be due in part to increased susceptibility to reduction and
      increased gastrointestinal absorption. C5-OHP-Cl is a suitable candidate for
      further study as an oral cancer chemotherapy agent.

PMID- 9923815
TI  - A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high
      dose carboplatin as primary treatment of patients with small-volume residual
      ovarian cancer.
AB  - PURPOSE: Because intraperitoneal (i.p.) therapy may provide a therapeutic
      advantage and because hyperthermia enhances carboplatin (CBDCA) cytotoxicity, we
      evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via
      continuous hyperthermic peritoneal perfusion (CHPP) in patients with small-volume
      residual ovarian cancer. PATIENTS AND METHODS: Six patients underwent optimal
      cytoreductive procedures (residual disease < or =5 mm) as initial treatment of
      stages II and III epithelial ovarian adenocarcinoma. All patients received a 90
      min CHPP at a CBDCA dose of 800-1200 mg/m2, with the perfusate being recirculated
      rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures
      of 41-43 degrees C. Plasma, perfusate, and urine samples were collected and
      platinum was quantified by flameless atomic absorption spectrophotometry.
      RESULTS: At no time did any patient's core temperature exceed 40 degrees C. Peak
      perfusate platinum concentrations were 8- to 15-fold higher than peak
      ultrafilterable plasma concentrations. The permeability-area product was
      extremely high and variable (14-90 ml/min), resulting in a regional advantage of
      1.9-5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose
      limiting hematologic toxicity was observed at a dose of 1200 mg/m2 and this was
      associated with a CBDCA AUC in plasma of 11 mg min ml(-1). CONCLUSION: CHPP with
      CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose
      limiting hematologic toxicities observed at 1200 mg/m2, correlated with the
      plasma CBDCA exposure established when lower doses of CBDCA are given
      systemically. The pharmacokinetic data are consistent with the expected effect of
      vigorous mixing on the exposed peritoneal surface area. Variable drug absorption
      and clearance make the prediction of systemic exposure highly uncertain. These
      findings may have important implications for novel therapies given i.p.

PMID- 9923816
TI  - In vitro pharmacology of cryptophycin 52 (LY355703) in human tumor cell lines.
AB  - PURPOSE: Cryptophycin 52 (LY355703) is a new member of the cryptophycin family of
      antitumor agents that is currently undergoing clinical evaluation for cancer
      chemotherapy. The mechanism of action of the cryptophycin class of compounds is
      associated with an action on microtubules. This report details the
      pharmacological profile of this new clinical compound in a panel of human tumor
      cell lines. METHODS: Antiproliferative effects of cryptophycin 52 were measured
      indirectly by detection of the metabolic reduction of alamarBlue. Cytoxicity was
      assessed by enzymatic dye activation (calcein AM) combined with dye exclusion
      (ethidium homodimer) and by clonogenicity assay. Cell cycle effects were
      evaluated using flow cytometry and fluorescence microscopy. RESULTS: Both
      antiproliferative and cytotoxic effects of cryptophycin 52 were concentration-
      and time-dependent. IC50 values for antiproliferative activity in both solid and
      hematologic tumor cell lines were in the low picomolar range, and without
      exception, were significantly below values for the antimitotic agents paclitaxel
      and vinblastine. Flow cytometry and microscopic examination of tumor cells
      treated with cryptophycin 52 indicated that they accumulated in the mitotic phase
      of the cell cycle. Cryptophycin 52 was tested for its sensitivity to multidrug
      resistance in several paired cell lines in which a sensitive parental line was
      matched with a multidrug-resistant derivative line. The resistant lines have been
      shown to over express Pgp and/or MRP multidrug-resistance transport factors.
      Compared to other antimitotic agents (paclitaxel, vinblastine, vincristine), the
      potency of cryptophycin 52 was shown to be minimally affected in multidrug
      resistant cells compared to their sensitive parental lines. CONCLUSION:
      Cryptophycin 52 has potent antimitotic, antiproliferative and cytotoxic activity
      in in vitro human tumor cell models. It is significantly more potent and less
      sensitive to multidrug resistance mechanisms than other antimitotic antitumor
      agents currently used in cancer therapy. These characteristics may translate into
      therapeutic advantages for the clinical use of cryptophycin 52 in cancer
      chemotherapy.

PMID- 9923817
TI  - Pharmacokinetics of dolasetron with coadministration of cimetidine or rifampin in
      healthy subjects.
AB  - PURPOSE: Dolasetron is a selective 5-HT3 receptor antagonist. The purpose of this
      study was to determine the effect of cimetidine and rifampin on the steady-state
      pharmacokinetics of orally administered dolasetron and its active reduced
      metabolite, hydrodolasetron. METHODS: A group of 18 healthy men (22 to 44 years
      old) were randomized to receive each of the following three treatments in a three
      period cross-over design: 200 mg dolasetron daily (treatment A); 200 mg
      dolasetron daily plus 300 mg cimetidine four times daily (treatment B); or 200 mg
      dolasetron daily plus 600 mg rifampin daily (treatment C). Each study period was
      separated by a 14-day washout period. Serial blood samples were collected before
      the first dose (baseline) on day 1 and at frequent intervals up to 48 h after the
      morning dose on day 7 for quantification of dolasetron and its metabolites,
      hydrodolasetron (both isomers), 5'OH hydrodolasetron, and 6'OH hydrodolasetron.
      Serial urine samples were also collected at baseline and during the periods 0-24
      and 24-48 h following the morning dose on day 7, and analyzed for dolasetron and
      its metabolites. RESULTS: Plasma and urine dolasetron concentrations were below
      quantifiable concentrations for all three treatments. Mean steady-state area
      under the plasma concentration-time curve (AUCss(0-24)) of hydrodolasetron
      increased by 24%, mean apparent clearance (CLapp.po) decreased by 19%, and
      maximum plasma hydrodolasetron concentration (Cmax,ss) increased by 15% when
      dolasetron was coadministered with cimetidine. When dolasetron was given with
      rifampin, mean hydrodolasetron AUCss(0-24) decreased by 28%, CLapp.po, increased
      by 39%, and hydrodolasetron Cmax,ss decreased by 17%. Small differences were
      found in mean tmax (0.7 to 0.8 h), CLr (2.0 to 2.6 ml/min per kg), and t1/2 (7.4
      to 8.8 h) for hydrodolasetron between treatment periods. Approximately 20% and 2%
      of the dolasetron dose were excreted in urine as the R(+) isomer and S(-) isomer
      of hydrodolasetron, respectively, across all three treatments. Dolasetron
      mesylate was well tolerated in this study during all three treatment periods,
      with the highest incidence of adverse events reported during the control period
      when dolasetron mesylate was given alone. CONCLUSION: Based on the small changes
      in the pharmacokinetic parameters of dolasetron and its active metabolites, as
      well as the favorable safety results, no dosage adjustments for dolasetron
      mesylate are recommended with concomitant administration of cimetidine or
      rifampin.

PMID- 9923818
TI  - Metabolism of 6-mercaptopurine in the erythrocytes, liver, and kidney of rats
      during multiple-dose regimens.
AB  - PURPOSE: To describe the metabolism of 6-mercaptopurine (6-MP) in erythrocytes
      and tissues of rats after repeated administration of 6-MP at two dose levels and
      to provide evidence that in vivo modulation of 6-MP anabolism can be obtained by
      simultaneous treatment with ribavirin or hydroxyurea, two inhibitors of enzymes
      involved in the bioactivation of 6-MP to the active 6-thioguanine nucleotides (6
      TGN). METHODS: Rats were treated i.p. with 6-MP at 12.5 and 25 mg/kg daily for 12
      days and erythrocyte, liver, and kidney levels of 6-mercaptopurine nucleotides (6
      MPN) and 6-TGN were investigated during the accumulation phase and for 50 days
      after the end of treatment. In combination studies, ribavirin at 75 and 100 mg/kg
      per day (for 6-MP, 25 and 12.5 mg/kg per day) or hydroxyurea at 200 mg/kg per day
      were given i.p. for 12 days. The measurements of thionucleotide levels in rat
      samples were performed by high-pressure liquid chromatography (HPLC). RESULTS:
      The maximal concentration (Cmax) and the area under the concentration versus time
      curve (AUC) of 6-MPN and 6-TGN in erythrocytes and tissues increased
      significantly after the administration of 6-MP at 25 mg/kg per day as compared
      with 12.5 mg/kg per day. In particular, the Cmax and AUC of 6-TGN in erythrocytes
      of rats treated with 6-MP at 25 mg/kg per day were approximately 5-fold higher
      than the 6-TGN values observed following treatment at 12.5 mg/kg per day.
      Moreover, 6-TGN levels in erythrocytes were significantly higher than those of 6
      MPN (910.9+/-53.1 and 286.8+/-23.4 pmol/8 x 10(8) cells for 6-TGN and 6-MPN,
      respectively, P < 0.05) after treatment with 6-MP at 25 mg/kg per day. The
      administration of ribavirin, an inhibitor of inosine monophosphate dehydrogenase,
      in association with 6-MP increased the amount of 6-MPN detected in erythrocytes
      and tissues while reducing 6-TGN levels in samples. The production and
      accumulation of 6-MPN and 6-TGN were increased in erythrocytes and tissues by
      hydroxyurea, an inhibitor of ribonucleotide reductase. Finally, a significant
      correlation between thionucleotide concentrations and erythrocyte counts was
      observed. CONCLUSION: The overall results demonstrate that 6-MP is actively
      metabolized in rats and that its biotransformation can be modulated by agents
      acting on enzymes of the purine metabolism, resulting in significant changes in
      erythrocyte and tissue levels of 6-MPN and 6-TGN. These findings provide evidence
      that the rat is a suitable model for investigation of the metabolism of 6-MP and
      its possible pharmacologic modulation.

PMID- 9923819
TI  - A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R)
      in patients with relapsed and refractory acute myeloid leukemia.
AB  - PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble
      truncated form of the type 1 full-length membrane-bound receptor that binds IL-1
      with identical affinity to that of the membrane form. As such, it may have
      clinical potential by sequestering IL-1, thereby preventing it from binding to
      its membrane-bound receptor and eliciting a biological effect. As IL-1 has been
      shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I
      trial of rhu IL-1R was conducted in patients with relapsed and refractory acute
      myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were
      sequentially treated on one of three dose levels, receiving a single intravenous
      (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.)
      injections with the option of an additional 14 days of treatment if a response of
      stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2,
      s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000
      microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v.
      bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to
      limited drug availability, the study was designed to only examine these three
      dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non
      hematological toxicity related to the study drug and the maximum tolerated dose
      was not reached. No IL-1R-blocking antibodies developed during the course of the
      study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during
      and after rhu IL-IR administration. The terminal half-life after i.v. dosing was
      at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to
      360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c.
      dosing respectively. No patient had a complete, partial or minor response to
      treatment; four had stable disease and seven had progressive disease.
      CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent
      antileukemic effect at the doses administered.

PMID- 9923821
TI  - Protection against doxorubicin-induced cardiotoxicity in weanling rats by
      dexrazoxane.
AB  - PURPOSE: Dexrazoxane (DZR) protects against anthracycline-induced cardiotoxicity
      in several laboratory animal species and in patients with breast cancer.
      Encouraging results have also been obtained in a limited number of pediatric
      oncology patients. We conducted studies to determine the safety and
      cardioprotective activity of DZR in the doxorubicin (DOX)-treated weanling rat
      simulating the rapidly growing immature child. METHODS: Male weanling rats and
      young adult rats, 20 days old and 7 weeks old, respectively, were given 1 mg/kg
      DOX i.v., either alone or with 20 mg/kg DZR, once weekly for 7 weeks. Rats were
      sacrificed at weeks 8, 12 or 26 following blood collection for hematology and
      serum chemistry. Hearts were weighed and examined histologically. RESULTS: DOX,
      either alone or with DZR, inhibited growth, and body weight remained below that
      of controls throughout the 26 weeks of study. There were no biologically
      significant hematologic changes in either the DOX- or DZR + DOX-treated young
      rats. DOX caused a slight increase in liver and kidney weights relative to body
      weight and a slight increase in serum cholesterol and triglycerides in the young
      rats. These effects were ameliorated or delayed by DZR. DOX, either alone or with
      DZR, caused a marked atrophy of the testes in the young rats which had recovered
      by week 26. In the mature rats, DOX caused a significant decrease in the WBC 1
      week after the last treatment, and the WBC was significantly lower in the rats
      given DZR + DOX compared to those given DOX alone. There were marked increases in
      liver and kidney weight, serum cholesterol and triglycerides in the mature rats
      given DOX alone but not in those given DZR + DOX. There was also a marked
      testicular atrophy in the mature rats given either DOX or DZR + DOX but, unlike
      that observed in the young rats, this had not returned to normal by week 26. DOX
      induced cardiotoxicity was less severe in the younger rats than in the mature
      rats but in both age groups, the lesion progressed rapidly until week 12, 5 weeks
      after the last dose, and remained relatively stable or progressed slightly
      thereafter. DZR provided significant cardioprotection in both age groups at all
      time points examined. Moreover, in both age groups, the severity of the
      cardiomyopathy in the DZR-treated rats was somewhat less at week 26 than it was
      at week 12. CONCLUSIONS: The results indicate that the pharmacologic effects of
      DZR, including its ability to protect against cardiotoxicity, are similar in
      immature and adult male animals treated with DOX.

PMID- 9923820
TI  - Activity of fenretinide plus chemotherapeutic agents in small-cell lung cancer
      cell lines.
AB  - PURPOSE: Fenretinide [N-(4-hydroxyphenyl)retinamide, 4HPR], a synthetic retinoid,
      is a potent inducer of apoptosis in small-cell lung cancer (SCLC) cell lines that
      may act through the generation of reactive oxygen species, suggesting that it may
      enhance the activity of other cytotoxic agents. In light of 4HPR's clinical
      potential and potent activity against SCLC cells, we evaluated the in vitro
      activity of 4HPR in combination with cisplatin, etoposide or paclitaxel. METHODS:
      The growth-inhibitory activities of single-agent 4HPR, cisplatin, etoposide or
      paclitaxel, and combinations of 4HPR and individual chemotherapeutic agents, were
      evaluated using an MTT assay in two SCLC cell lines. Each two-drug combination
      was studied over a range of concentrations at a fixed ratio corresponding to the
      ratio of the IC5 values of the individual agents. Data were analyzed by median
      effect analysis as previously applied to drug combination studies. RESULTS: All
      four agents inhibited growth in a dose-dependent manner in the NCI-H82 and NCI
      H446 SCLC cell lines. At clinically reported drug concentrations that resulted in
      over 50% growth inhibition, the activities of the combinations 4HPR and cisplatin
      and 4HPR and etoposide were more than additive in both cell lines, and the
      activity of 4HPR plus paclitaxel was more than additive in NCI-H446 cells.
      CONCLUSION: 4HPR's potent single-agent activity, minimal toxicity, and potential
      synergy with standard cytotoxic drugs will allow for the development of promising
      investigational regimens for the treatment of patients with SCLC.

PMID- 9923822
TI  - Failure of oral nitrate and calcium channel blocker therapy to prevent 5
      fluorouracil-related myocardial ischemia: a case report.
AB  - BACKGROUND: Myocardial ischemia induced by 5-fluorouracil (5-FU) is a relatively
      rare, but potentially serious, occurrence. Some case reports have indicated that
      recurrent ischemia may be prevented if 5-FU is resumed after pretreatment with
      antianginal therapy. METHODS: A 54-year old woman was diagnosed with stage IIA
      squamous cell carcinoma of the anus. Treatment with concurrent radiation and
      chemotherapy (mitomycin-C and 5-FU) was initiated with curative intent. RESULTS:
      The patient had no evidence of underlying coronary artery disease based on
      history, physical examination or ECG. Approximately 48 h after initiation of 5-FU
      infusion the patient developed anginal pain associated with ECG changes
      compatible with ischemia. After resolution of ischemia and ruling out of
      myocardial infarction, coronary arteriography demonstrated normal coronary
      arteries. In an attempt to prevent myocardial ischemia, calcium channel blocker
      and nitrate therapy was started, but anginal pain with ECG change recurred when 5
      FU was resumed. This necessitated selection of an alternative chemotherapy
      regimen. CONCLUSIONS: Even in the presence of normal coronary arteries,
      antianginal therapy may not preclude the occurrence of potentially serious 5-FU
      induced myocardial ischemia. For patients who experience 5-FU-induced myocardial
      ischemia, development of alternative chemotherapy regimens should be considered.

PMID- 9923823
TI  - Phase II study of CI-958 in colorectal cancer.
AB  - PURPOSE: We completed a phase II trial of CI-958 (NSC 635371) in patients with
      advanced colorectal cancer given at a dose of 700 mg/m2 every 21 days. METHODS:
      All 15 patients had metastatic disease and had been previously treated with one 5
      fluorouracil-based regimen in an adjuvant (six) or metastatic (nine) setting.
      RESULTS: None of the patients treated with CI-958 had an objective response to
      treatment. Median survival was 4.8 months after the start of treatment.
      Leukopenia was the major toxicity, but no patient experienced febrile
      neutropenia. An acute febrile reaction was seen after infusion in four of the
      first nine patients treated. This was abrogated by pretreatment with
      dexamethasone in the remaining patients. CONCLUSIONS: CI-958 was not effective at
      this dose and schedule in patients with previously treated advanced colorectal
      cancer.

PMID- 9923824
TI  - Lack of correlation between mitotic arrest or apoptosis and antitumor effect of
      docetaxel.
AB  - PURPOSE: To determine, as we did for paclit-axel, whether mitotic arrest and
      apoptosis induced in murine tumors in vivo by docetaxel correlate with the drug's
      antitumor effect and whether the antitumor efficacy of docetaxel depends on p53
      mutational status of tumors. METHODS: C3Hf/Kam mice were implanted with one of
      the following 15 syngeneic tumors: seven adenocarcinomas (MCa-4, MCa-29, MCa-35,
      MCa-K, OCa-I, ACa-SG, and HCa-I), two squamous cell carcinomas (SCC-IV and SCC
      VII), five sarcomas (FSa, FSa-II, Sa-NH, NFSa, and Sa-4020) and one lymphoma (Ly
      TH). When the tumors had grown to 8 mm in diameter, the mice were treated with
      31.3 mg/kg docetaxel i.v. Tumor growth delay was the endpoint of docetaxel's
      antitumor effect. In separate groups of mice, mitotic arrest and apoptosis were
      determined micromorphometrically 1 to 72 h after docetaxel treatment. Tumors were
      assayed for their p53 status by sequence analysis of RNA prepared from freshly
      excised tumors. RESULTS: Docetaxel caused statistically significant growth delay
      in six of seven adenocarcinomas, three of five sarcomas, and the lymphoma, but
      not in either of the squamous cell carcinomas. The drug induced mitotic arrest in
      all tumor types, but to various degrees ranging from 6.4+/-0.4% to 25.1+/-0.1%.
      In contrast, docetaxel induced appreciable apoptosis in only 5 of 15 tumors, with
      10.3+/-1.6% being the highest apoptotic value. Neither mitotic arrest nor
      apoptosis were significantly correlated with tumor growth delay. However, tumors
      that responded to docetaxel by significant tumor growth delay histologically
      displayed massive cell destruction by cell lysis, and four of these tumors also
      showed marked infiltration with mononuclear lymphoid cells. Of the 15 tumors only
      3 had mutant p53. CONCLUSIONS: Docetaxel exhibited a strong antitumor effect in
      two-thirds of murine tumors, and on a milligram per kilogram basis was more
      effective than paclitaxel against the same tumors. The drug was a potent inducer
      of mitotic arrest but a weak inducer of apoptosis, neither of which correlated
      with its antitumor effect. Tumor cell lysis appeared to be a major mode of tumor
      cell destruction and can be regarded as the main mechanism underlying antitumor
      efficacy of docetaxel. In contrast, paclitaxel's antitumor efficacy is related to
      its ability to induce apoptosis. At the molecular level, there was no dependency
      of antitumor efficacy of docetaxel on p53 mutational status of tumors.

PMID- 9923825
TI  - The venotonic drug hydroxyethylrutosiden does not prevent or reduce docetaxel
      induced fluid retention: results of a comparative study.
AB  - PURPOSE: Fluid retention, which includes peripheral edema, ascites, pleural or
      pericardial effusion, or a combination of these that is sometimes associated with
      significant weight gain, is one of the most troublesome cumulative side effects
      of docetaxel. A suggestive observation from the data base available at the
      manufacturer (Rhone-Poulenc Rorer) was that patients who received venotonic drugs
      appeared to tolerate more courses of docetaxel. This prompted a comparative study
      to investigate whether the venotonic drug hydroxyethylrutosiden could reduce or
      delay docetaxel-related fluid retention. METHODS: A total of 85 patients with
      metastatic breast cancer who were treated with docetaxel at a dose of 100 mg/m2
      with corticoid comedication were allocated to receive either 300 mg
      hydroxyethylrutosiden given orally four times daily (group A) or no
      hydroxyethylrutosiden (group B). The end point for analysis was the development
      of fluid retention of > or = grade 2. RESULTS: Fluid retention of > or = grade 2
      was reported in 14 of 42 patients (33%) in group A and in 15 of 43 patients (35%)
      in group B and occurred after a median of 4 cycles of docetaxel in both groups.
      Weight gain was similar in groups A and B. CONCLUSION: We conclude that
      hydroxyethylrutosiden does not reduce or delay the incidence and severity of
      docetaxel-related fluid retention.

PMID- 9923826
TI  - Safety and potential effectiveness of daunorubicin-containing liposomes in
      patients with advanced recurrent malignant CNS tumors.

PMID- 9923827
TI  - Vinorelbine-related acute cardiopulmonary toxicity.
AB  - Three cases of possible acute cardiopulmonary toxicity following the
      administration of vinorelbine are reported. The symptoms mimicked acute cardiac
      ischemia. However, neither ECG changes nor elevations of serum enzymes were
      observed. The outcome is favorable in 90% of patients developing this adverse
      event. The putative mechanism remains to be elucidated.

PMID- 9923828
TI  - Percivall Pott.

PMID- 9923829
TI  - Protocols for the examination of tumors of diverse sites: introduction. Cancer
      Committee, College of American Pathologists.
AB  - This issue of the ARCHIVES includes previously unpublished protocols for the
      examination of specimens removed from patients with cancer of diverse sites. We
      provide a historical context for the development of these protocols and describe
      the process of development and approval. General information about the structure
      and content of the protocols is also provided. Cancer protocol development is an
      important step in the process of standardized cancer reporting. The value of such
      standardized reporting is discussed.

PMID- 9923831
TI  - Protocol for the examination of specimens from patients with primary cardiac
      tumors: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923830
TI  - Protocol for the examination of specimens from patients with malignant germ cell
      and sex cord-stromal tumors of the testis, exclusive of paratesticular
      malignancies: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923832
TI  - Protocol for the examination of specimens from patients with carcinomas of renal
      tubular origin, exclusive of Wilms tumor and tumors of urothelial origin: a basis
      for checklists. Cancer Committee, College of American Pathologists.

PMID- 9923833
TI  - Protocol for the examination of specimens from patients with carcinomas of the
      endometrium: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923835
TI  - Protocol for the examination of specimens from patients with malignant pleural
      mesothelioma: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923834
TI  - Protocol for the examination of specimens from patients with carcinoma of the
      fallopian tube: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923836
TI  - Protocol for the examination of specimens from patients with malignant tumors of
      the thyroid gland, exclusive of lymphomas: a basis for checklists. Cancer
      Committee, College of American Pathologists.

PMID- 9923837
TI  - Protocol for the examination of specimens from patients with gestational
      trophoblastic malignancies: a basis for checklists. Cancer Committee, College of
      American Pathologists.

PMID- 9923838
TI  - Protocol for the examination of specimens from patients with carcinomas of the
      cervix: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923839
TI  - Protocol for the examination of specimens from patients with carcinoma of the
      vagina: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923840
TI  - Protocol for the examination of specimens from patients with non-Hodgkin's
      lymphoma: a basis for checklists. Cancer Committee, College of American
      Pathologists.

PMID- 9923841
TI  - Protocol for the examination of specimens from patients with Hodgkin's disease: a
      basis for checklists. Cancer Committee, College of American Pathologists.

PMID- 9923842
TI  - Infection in a cystic fibrosis patient.

PMID- 9923843
TI  - Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder
      of the brain presenting as human immunodeficiency virus-associated encephalopathy
      in a child with acquired immunodeficiency syndrome.
AB  - The association of the Epstein-Barr virus with human immunodeficiency virus
      associated primary central nervous system lymphomas is well known. We describe a
      pediatric patient infected with human immunodeficiency virus who developed a
      lesion in the central nervous system that appeared to be histologically reactive
      and that proved to be an Epstein-Barr virus-associated monoclonal B-cell
      lymphoproliferative disorder by molecular analysis. An 8-year-old girl was
      diagnosed with vertically transmitted human immunodeficiency virus infection at
      age 5, for which she was treated empirically with a combination of zidovudine and
      didanosine. At the age of 7 years, during evaluation for entry into an
      antiretroviral protocol, a single hypodense frontal lobe lesion was identified by
      computed tomography. After unsuccessful treatment for presumed toxoplasmosis and
      progressive neurologic deterioration, a stereotactic brain biopsy was performed.
      Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to
      be cytologically reactive, polymerase chain reaction and in situ hybridization
      studies revealed a monoclonal Epstein-Barr virus-associated B-cell
      lymphoproliferative disorder, which was reminiscent of polymorphic B-cell
      hyperplasia observed in the setting of immunosuppression following organ
      transplantation. Postoperative therapy included steroids and antiretroviral
      therapy. The lesion decreased slightly in size, and the child's neurologic status
      was relatively unremarkable for 5 months. Subsequently, she developed
      cytomegalovirus retinitis, progressive encephalopathy, and died with
      pancytopenia. This case represents a newly described manifestation of Epstein
      Barr virus-associated lymphoproliferative disorder, a diagnosis that should be
      considered in patients with neurologic symptoms and immunodeficiency. In
      addition, this case exhibited histologic features reminiscent of posttransplant
      lymphoproliferative disease, a histologic pattern that to our knowledge has not
      previously been reported in the setting of acquired immunodeficiency syndrome.

PMID- 9923844
TI  - A Bcr/Abl kinase antagonist for chronic myelogenous leukemia: a promising path
      for progress emerges.

PMID- 9923845
TI  - The butler did it: search for killer(s) of Kaposi's sarcoma cells in preparations
      of human chorionic gonadotropin.

PMID- 9923847
TI  - Thanks, but no thanks: breast cancer group declines funding.

PMID- 9923846
TI  - aHIF: the missing link between HIF-1 and VHL?

PMID- 9923848
TI  - Using HER2 to choose chemotherapy in breast cancer: is it ready for the clinic?

PMID- 9923850
TI  - Giving new meaning to the word "watchdog"?

PMID- 9923849
TI  - How should HER2 status be determined?

PMID- 9923851
TI  - What ever happened to ...?: A 10-year retrospective.

PMID- 9923852
TI  - British commence war on tobacco.

PMID- 9923853
TI  - Cell and molecular biology of simian virus 40: implications for human infections
      and disease.
AB  - Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered
      in 1960 as a contaminant of polio vaccines that were distributed to millions of
      people from 1955 through early 1963. SV40 is a potent DNA tumor virus that
      induces tumors in rodents and transforms many types of cells in culture,
      including those of human origin. This virus has been a favored laboratory model
      for mechanistic studies of molecular processes in eukaryotic cells and of
      cellular transformation. The viral replication protein, named large T antigen (T
      ag), is also the viral oncoprotein. There is a single serotype of SV40, but
      multiple strains of virus exist that are distinguishable by nucleotide
      differences in the regulatory region of the viral genome and in the part of the T
      ag gene that encodes the protein's carboxyl terminus. Natural infections in
      monkeys by SV40 are usually benign but may become pathogenic in immunocompromised
      animals, and multiple tissues can be infected. SV40 can replicate in certain
      types of simian and human cells. SV40-neutralizing antibodies have been detected
      in individuals not exposed to contaminated polio vaccines. SV40 DNA has been
      identified in some normal human tissues, and there are accumulating reports of
      detection of SV40 DNA and/or T-ag in a variety of human tumors. This review
      presents aspects of replication and cell transformation by SV40 and considers
      their implications for human infections and disease pathogenesis by the virus.
      Critical assessment of virologic and epidemiologic data suggests a probable
      causative role for SV40 in certain human cancers, but additional studies are
      necessary to prove etiology.

PMID- 9923854
TI  - Induction of programmed cell death in Kaposi's sarcoma cells by preparations of
      human chorionic gonadotropin.
AB  - BACKGROUND: Isolation of the first neoplastic acquired immunodeficiency syndrome
      related Kaposi's sarcoma (KS) cell line (KS Y-1) has furthered understanding of
      the pathogenesis of KS. Studies with KS Y-1 cells have indicated that inhibition
      of KS cell proliferation occurs in early pregnancy in mice and after treatment
      with certain commercial preparations of human chorionic gonadotropin (hCG, a
      pregnancy hormone purified from urine). The activity of the commercial
      preparations has been attributed to an hCG-associated factor(s) (HAF). While
      several clinical benefits of HAF are clearly evident, the basis for its anti-KS
      properties remains unknown. We investigated the apoptosis-inducing effects of HAF
      and the expression of apoptosis-related proteins in KS cells. METHODS: KS Y-1 and
      KS SLK cells were treated with clinical-grade crude preparations of hCG,
      recombinant hCG, or urine fractions exhibiting anti-KS activity and then examined
      for features of apoptosis. Levels of proteins associated with apoptosis were
      monitored by western blot analysis, and cell DNA content was assessed by flow
      cytometry. Tumors induced in mice by inoculation of KS Y-1 cells were treated
      with preparations of hCG, and the tumors were examined for cell morphology and
      also for DNA fragmentation by use of the terminal deoxynucleotidyl transferase
      mediated digoxigenin-deoxyuridine triphosphate nick-end-labeling (TUNEL) assay.
      RESULTS: The HAF present in some preparations of hCG and in urine fractions has
      the ability to induce apoptosis in KS cells in vitro and in vivo. HAF-triggered
      apoptosis was preceded by increased levels of the apoptosis-related proteins c
      Myc and c-Rel and cell accumulation in Go/G1 phase of the cell cycle. KS Y-1
      cells transfected with a c-Myc complementary DNA showed elevated rates of
      apoptosis. CONCLUSION: The anti-KS activity of HAF appears to induce apoptosis.
      Such activity suggests a role for HAF in pregnancy-related regulation of cell
      death.

PMID- 9923856
TI  - Plasma levels of insulin-like growth factor-I and lung cancer risk: a case
      control analysis.
AB  - BACKGROUND: Insulin-like growth factors (IGFs), in particular IGF-I and IGF-II,
      strongly stimulate the proliferation of a variety of cancer cells, including
      those from lung cancer. To examine the possible causal role of IGFs in lung
      cancer development, we compared plasma levels of IGF-I, IGF-II, and an IGF
      binding protein (IGFBP-3) in patients with newly diagnosed lung cancer and in
      control subjects. METHODS: From an ongoing hospital-based, case-control study, we
      selected 204 consecutive patients with histologically confirmed, primary lung
      cancer and 218 control subjects who were matched to the case patients by age,
      sex, race, and smoking status. IGF-I, IGF-II, and IGFBP-3 plasma levels were
      measured by enzyme-linked immunosorbent assay and then divided into quartiles,
      based on their distribution in the control subjects. Associations between the IGF
      variables and lung cancer risk were estimated by use of odds ratios (ORs).
      Reported P values are two-sided. RESULTS: IGF and IGFBP-3 levels were positively
      correlated (all r>.27; all P<.001). High plasma levels of IGF-I were associated
      with an increased risk of lung cancer (OR = 2.06; 95% confidence interval [CI] =
      1.19-3.56; P = .01), and this association was dose dependent in both univariate
      and multivariate analyses. Plasma IGFBP-3 showed no association with lung cancer
      risk unless adjusted for IGF-I level; when both of these variables were analyzed
      together, high plasma levels of IGFBP-3 were associated with reduced risk of lung
      cancer (OR = 0.48; 95% CI = 0.25-0.92; P = .03). IGF-II was not associated with
      lung cancer risk. CONCLUSIONS: Plasma levels of IGF-I are higher and plasma
      levels of IGFBP-3 are lower in patients with lung cancer than in control
      subjects. If these findings can be confirmed in prospective studies, measuring
      levels of IGF-I and IGFBP-3 in blood may prove useful in assessing lung cancer
      risk.

PMID- 9923857
TI  - Human papillomavirus infection and esophageal cancer: a nationwide
      seroepidemiologic case-control study in Sweden.
AB  - BACKGROUND: Infection with human papillomavirus (HPV) type 16 has been implicated
      as a risk factor for esophageal squamous cell carcinoma in three
      seroepidemiologic studies. We conducted a larger, population-based study to
      verify this association and to investigate possible confounding factors. METHODS:
      We performed a nationwide case-control study in Sweden of HPV16 or HPV18
      infection and risk of esophageal squamous cell carcinoma or
      esophageal/gastroesophageal adenocarcinoma. Tumors were strictly classified by
      their location and histologic type. Case subjects with incident cancers and
      population-based control subjects donated blood samples and were interviewed in
      person about potential confounding factors. An enzyme-linked immunosorbent assay
      was used to detect HPV seropositivity. Multivariate analyses were conducted to
      study relationships between HPV seropositivity, level of education, smoking (all
      tobacco) status, alcohol consumption, and cancer risk. RESULTS: We compared 121
      case subjects with esophageal squamous cell carcinoma and 173 case subjects with
      adenocarcinoma of the esophagus or gastroesophageal junction with 302 population
      based control subjects. The age- and sex-adjusted odds ratios (ORs) for squamous
      cell carcinoma were 1.0 (95% confidence interval [CI] = 0.5-2.0) for persons
      seropositive for HPV16 and 0.5 (95% CI = 0.2-1.1) for persons seropositive for
      HPV18 in comparison with seronegative individuals. The corresponding ORs for
      adenocarcinoma were 1.2 (95% CI = 0.7-2.2) and 0.2 (95% CI = 0.1-0.7),
      respectively. Adjustments for smoking status, alcohol consumption, and level of
      education did not alter the results. CONCLUSIONS: We found no evidence of a
      positive association between HPV16 or HPV18 infection and either form of
      esophageal cancer. Our results do not support conclusions from previous studies.

PMID- 9923855
TI  - aHIF: a natural antisense transcript overexpressed in human renal cancer and
      during hypoxia.
AB  - BACKGROUND: Nonpapillary renal carcinoma is the predominant form of human kidney
      cancer and represents a distinct disease entity, morphologically and molecularly,
      from papillary renal carcinoma. We have discovered a natural antisense transcript
      that is complementary to the 3' untranslated region of hypoxia inducible factor
      alpha (HIF1alpha) messenger RNA (mRNA) and is strikingly overexpressed
      specifically in nonpapillary kidney cancer. HIF1alpha encodes a protein that is
      known to have two important functions: 1) to act as a transcription factor for
      hypoxia inducible genes and 2) to stabilize p53 protein during hypoxia. Because
      of the importance of HIF1alpha, we have characterized this natural antisense
      transcript, which we have named "aHIF." METHODS: Differential display, reverse
      transcription-polymerase chain reaction, ribonuclease protection, and DNA
      sequencing methods were used in our analysis. RESULTS AND CONCLUSIONS: We show
      the following: 1) aHIF is a natural antisense transcript derived from HIF1alpha
      gene sequences encoding the 3' untranslated region of HIF1alpha mRNA; 2) aHIF is
      specifically overexpressed in all nonpapillary clear-cell renal carcinomas
      examined, but not in the papillary renal carcinomas examined; 3) aHIF is
      overexpressed in an established nonpapillary renal carcinoma cell line under both
      normoxic (i.e., normal aerobic) and hypoxic conditions; and 4) although aHIF is
      not further induced by hypoxia in nonpapillary disease, it can be induced in
      lymphocytes where there is a concomitant decrease in HIF1alpha mRNA. To our
      knowledge, this is the first case of overexpression of a natural antisense
      transcript exclusively associated with a specific human malignant disease.

PMID- 9923858
TI  - In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase
      inhibitor.
AB  - BACKGROUND: The leukemia cells of approximately 95% of patients with chronic
      myeloid leukemia and 30%-50% of adult patients with acute lymphoblastic leukemia
      express the Bcr/Abl oncoprotein, which is the product of a fusion gene created by
      a chromosomal translocation [(9:22) (q34;q11)]. This oncoprotein expresses a
      constitutive tyrosine kinase activity that is crucial for its cellular
      transforming activity. In this study, we evaluated the antineoplastic activity of
      CGP57148B, which is a competitive inhibitor of the Bcr/Abl tyrosine kinase.
      METHODS: Nude mice were given an injection of the Bcr/Abl-positive human leukemia
      cell lines KU812 or MC3. Tumor-bearing mice were treated intraperitoneally or
      orally with CGP57148B according to three different schedules. In vitro drug wash
      out experiments and in vivo molecular pharmacokinetic experiments were performed
      to optimize the in vivo treatment schedule. RESULTS: Treatment schedules
      administering CGP57148B once or twice per day produced some inhibition of tumor
      growth, but no tumor-bearing mouse was cured. A single administration of
      CGP57148B caused substantial (>50%) but short-lived (2-5 hours) inhibition of
      Bcr/Abl kinase activity. On the basis of the results from in vitro wash-out
      experiments, 20-21 hours was defined as the duration of continuous exposure
      needed to block cell proliferation and to induce apoptosis in these two leukemia
      cell lines. A treatment regimen assuring the continuous block of the Bcr/Abl
      phosphorylating activity that was administered over an 11-day period cured 87%
      100% of treated mice. CONCLUSION: These data indicate that the continuous block
      of the oncogenic tyrosine kinase of Bcr/Abl protein is needed to produce
      important biologic effects in vivo.

PMID- 9923859
TI  - Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector
      encoding safety-modified simian virus 40 T antigen.
AB  - BACKGROUND: Evidence that simian virus 40 (SV40) is associated with human
      mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant
      vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could
      have clinical utility. To address this potential need, we designed a novel
      vaccinia virus construct that encodes an SV40 Tag in which oncogenic domains were
      excluded and immunogenic domains were preserved. We named this recombinant
      construct vaccinia-encoding safety-modified SV40 Tag (vac-mTag). METHODS:
      Purified vac-mTag was characterized by DNA sequencing, reverse transcription
      coupled polymerase chain reaction, western blot analysis, and immunocytochemical
      techniques. Induction of Tag-specific immunity was examined by cytolytic T-cell
      assays, and the efficacy of vac-mTag in protecting animals against Tag-expressing
      tumors and in treating pre-established microscopic tumors was evaluated in vac
      mTag-immunized BALB/c mice. RESULTS: The immune response elicited by vac-mTag in
      C57BL/6 and BALB/c mice included an SV40 Tag-specific cytolytic T-lymphocyte
      activity against syngeneic (identical genetic background) SV40 Tag-expressing
      tumor targets. Immunization of mice with a single dose of vac-mTag resulted in
      potent protection against subsequent challenge with a lethal mouse cancer
      expressing SV40 Tag. In addition, single-dose vac-mTag immunization
      coadministered with interleukin 2 produced a possible therapeutic effect against
      a preadministered microscopic (but lethal) burden of Tag-expressing tumor cells
      in vivo. CONCLUSION: vac-mTag induces an effective immune response in mice that
      is specific for a tumor-associated antigen. This response protects against a
      lethal tumor challenge and results in a possible therapeutic effect against Tag
      expressing tumors in vivo. Thus, vac-mTag provides a new avenue for the
      development of therapies for human cancers thought to be associated with SV40.

PMID- 9923860
TI  - Influence of dietary calcium and vitamin D on diet-induced epithelial cell
      hyperproliferation in mice.
AB  - BACKGROUND: Previous epidemiologic and laboratory studies, including some from
      our own laboratory, have suggested that a high-fat diet increases risk of cancer
      development in the pancreas, prostate, colon, and breast and that carcinogenesis
      in some of these organs may be influenced by alterations in dietary calcium and
      vitamin D. In this study, we sought to investigate the effect of added dietary
      calcium or vitamin D on the development of epithelial cell hyperproliferation
      induced by a Western-style diet in the exocrine pancreas, prostate, and mammary
      gland of mice. METHODS: Four-week-old C57BL/6J mice were given either a control
      diet (American Institute of Nutrition [AIN]-76A), a Western-style diet
      (containing reduced calcium and vitamin D and the fat level of the average human
      Western diet), or a putative chemopreventive diet (a Western-style diet with the
      addition of dietary calcium and vitamin D). Nine weeks after dietary
      intervention, osmotic pumps were implanted in the mice to provide 3 days of
      bromodeoxyuridine (BrdU) infusion. All P values are two-sided. RESULTS: Mice on
      the Western-style diet had statistically significant increases in BrdU-labeling
      indices of epithelial cells in the interlobular (P = .015) and intralobular (P =
      .012) ducts and centroacinar cells (P = .001) of the pancreatic duct system, the
      dorsal lobe of the prostate (P = .045), and the terminal ducts of the mammary
      gland (P = .032), compared with mice in the respective control diet groups.
      Adding dietary calcium and vitamin D markedly suppressed the Western-style diet
      induced hyperproliferation of epithelial cells in those tissues (P = .001-.033).
      CONCLUSIONS: This study confirms previous findings that a Western-style diet
      produces hyperproliferation of epithelial cells in several organs and that the
      changes can be prevented by increasing dietary calcium and vitamin D alone.

PMID- 9923861
TI  - Role of various carotenoids in lung cancer prevention.

PMID- 9923862
TI  - How adolescents get their cigarettes: implications for policies on access and
      price.

PMID- 9923864
TI  - Unexplained deaths in infancy.

PMID- 9923863
TI  - Re: Tamoxifen for prevention of breast cancer: report of the National Surgical
      Adjuvant Breast and Bowel Project P-1 study.

PMID- 9923865
TI  - Bridging the gulf in war syndromes.

PMID- 9923866
TI  - Antemortem diagnosis of variant Creutzfeldt-Jakob disease.

PMID- 9923867
TI  - The information wars.

PMID- 9923868
TI  - Therapy for retinopathy of prematurity.

PMID- 9923869
TI  - Allergy priming early in life.

PMID- 9923870
TI  - Protective effects of erythema nodosum in coccidioidomycosis.

PMID- 9923871
TI  - Health of UK servicemen who served in Persian Gulf War.
AB  - BACKGROUND: Various symptoms in military personnel in the Persian Gulf War 1990
      91 have caused international speculation and concern. We investigated UK
      servicemen. METHODS: We did a cross-sectional postal survey on a random sample of
      Gulf War veterans (Gulf War cohort, n=4248) and, stratified for age and rank,
      servicemen deployed to the Bosnia conflict (Bosnia cohort, n=4250) and those
      serving during the Gulf War but not deployed there (Era cohort, n=4246). We asked
      about deployment, exposures, symptoms, and illnesses. We analysed men only. Our
      outcome measures were physical health, functional capacity (SF-36), the general
      health questionnaire, the Centers for Disease Control and Prevention (CDC)
      multisymptom criteria for Gulf War illness, and post-traumatic stress reactions.
      FINDINGS: There were 8195 (65.1%) valid responses. The Gulf War cohort reported
      symptoms and disorders significantly more frequently than those in the Bosnia and
      Era cohorts, which were similar. Perception of physical health and ability were
      significantly worse in the Gulf War cohort than in the other cohorts, even after
      adjustment for confounders. Gulf War veterans were more likely than the Bosnia
      cohort to have substantial fatigue (odds ratio 2.2 [95% CI 1.9-2.6]), symptoms of
      post-traumatic stress (2.6 [1.9-3.4]), and psychological distress (1.6 [1.4
      1.8]), and were nearly twice as likely to reach the CDC case definition (2.5 [2.2
      2.8]). In the Gulf War, Bosnia, and Era cohorts, respectively, 61.9%, 36.8%, and
      36.4% met the CDC criteria, which fell to 25.3%, 11.8%, and 12.2% for severe
      symptoms. Potentially harmful exposures were reported most frequently by the Gulf
      War cohort. All exposures showed associations with all of the outcome measures in
      the three cohorts. Exposures specific to the Gulf were associated with all
      outcomes. Vaccination against biological warfare and multiple routine
      vaccinations were associated with the CDC multisymptom syndrome in the Gulf War
      cohort. INTERPRETATION: Service in the Gulf War was associated with various
      health problems over and above those associated with deployment to an unfamiliar
      hostile environment. Since associations of ill health with adverse events and
      exposures were found in all cohorts, however, they may not be unique and causally
      implicated in Gulf-War-related illness. A specific mechanism may link vaccination
      against biological warfare agents and later ill health, but the risks of illness
      must be considered against the protection of servicemen.

PMID- 9923872
TI  - Is there a Gulf War syndrome?
AB  - BACKGROUND: UK veterans of the Gulf War report more ill health than servicemen
      who were not deployed to the Gulf War. We investigated whether the pattern of
      symptom reporting by veterans of the Gulf War differed from that in active
      servicemen who had not fought in the Gulf War or who had fought in other
      conflicts. METHODS: We used a population-based cross-sectional design. We sent a
      standardised survey that asked about 50 physical symptoms to three UK military
      cohorts; men who had served in the Gulf War, those who had served in the Bosnia
      conflict, and men who had been in active service but not deployed to the Gulf War
      (Era cohort). We used exploratory factor analysis to identify underlying factors
      and describe the factor structure of the symptoms reported in the Gulf War
      cohort. Confirmatory factor analysis was used to test the fit of this factor
      structure in the Bosnia and Era cohorts. FINDINGS: Three factors in the Gulf War
      cohort together accounted for about 20% of the common variance. We labelled the
      factors mood, respiratory system, and peripheral nervous system, according to the
      symptoms that loaded on to them. In the confirmatory factor analysis, the factor
      structure identified in the Gulf War cohort fitted reasonably well in the Bosnia
      and Era cohorts. INTERPRETATION: Although results from complex modelling
      procedures need to be interpreted with caution, our findings do not support a
      unique Gulf War syndrome. The mechanisms behind increased self-reporting of
      symptoms need further investigation.

PMID- 9923873
TI  - Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases
      with tonsil biopsy samples.
AB  - BACKGROUND: Prion diseases are associated with the accumulation of an abnormal
      isoform of cellular prion protein (PrPSc), which is the principal constituent of
      prions. Prions replicate in lymphoreticular tissues before neuroinvasion,
      suggesting that lymphoreticular biopsy samples may allow early diagnosis by
      detection of PrPSc. Variant Creutzfeldt-Jakob disease (variant CJD) is difficult
      to distinguish from common psychiatric disorders in its early stages and
      definitive diagnosis has relied on neuropathology. We studied lymphoreticular
      tissues from a necropsy series and assessed tonsillar biopsy samples as a
      diagnostic investigation for human prion disease. METHODS: Lymphoreticular
      tissues (68 tonsils, 64 spleens, and 40 lymph nodes) were obtained at necropsy
      from patients affected by prion disease and from neurological and normal
      controls. Tonsil biopsy sampling was done on 20 patients with suspected prion
      disease. Tissues were analysed by western blot to detect and type PrPSc, by PrP
      immunohistochemistry, or both. FINDINGS: All lymphoreticular tissues obtained at
      necropsy from patients with neuropathologically confirmed variant CJD, but not
      from patients with other prion diseases or controls, were positive for PrPSc. In
      addition, PrPSc typing revealed a consistent pattern (designated type 4t)
      different from that seen in variant CJD brain (type 4) or in brain from other CJD
      subtypes (types 1-3). Tonsil biopsy tissue was positive in all eight patients
      with an adequate biopsy sample and whose subsequent course has confirmed, or is
      highly consistent with, a diagnosis of variant CJD and negative in all patients
      subsequently confirmed to have other diagnoses. INTERPRETATION: We found that if,
      in the appropriate clinical context, a tonsil biopsy sample was positive for
      PrPSc, variant CJD could be diagnosed, which obviates the need for a brain biopsy
      sample to be taken. Our results also show that variant CJD has a different
      pathogenesis to sporadic CJD.

PMID- 9923874
TI  - Non-invasive diagnosis of venous thromboembolism in outpatients.
AB  - BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute
      venous thromboembolism based on clinical probability assessment of deep-vein
      thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower
      limb venous compression ultrasonography, and lung scan to reduce the need for
      phlebography and pulmonary angiography. METHODS: 918 consecutive patients
      presenting at the emergency ward of the Geneva University Hospital, Geneva,
      Switzerland, and Hopital Saint-Luc, Montreal, Canada, with clinically suspected
      venous thromboembolism were entered into a sequential diagnostic protocol.
      Patients in whom venous thromboembolism was deemed absent were not given
      anticoagulants and were followed up for 3 months. FINDINGS: A normal D-dimer
      concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism
      in 286 (31%) members of the study cohort, whereas DVT by ultrasonography
      established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of
      the remaining patients. Venous thromboembolism was also deemed absent in patients
      with low to intermediate clinical probability of DVT and a normal venous
      ultrasonography (236 [26%] patients), and in patients with a low clinical
      probability of PE and a non-diagnostic result on lung scan (107 [12%] patients).
      Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of
      the patients, respectively. Hence, a non-invasive diagnosis was possible in 866
      (94%) members of the entire cohort. The 3-month thromboembolic risk in patients
      not given anticoagulants, based on the results of the diagnostic protocol, was
      1.8% (95% CI 0.9-3.1). INTERPRETATION: A diagnostic strategy combining clinical
      assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis
      in the vast majority of outpatients with suspected venous thromboembolism, and
      appeared to be safe.

PMID- 9923875
TI  - Development of allergen-specific T-cell memory in atopic and normal children.
AB  - BACKGROUND: In the past 20-30 years, there has been an increase in prevalence of
      allergic respiratory diseases, particularly amongst children. This study is a
      prospective analysis of the postnatal maturation of T-helper cell (Th) responses
      to aeroallergens in atopic and non-atopic infants. METHODS: We measured
      mononuclear-cell proliferative and cytokine responses to specific allergens and
      tetanus toxoid in blood samples from atopic and non-atopic infants every 6 months
      from birth to 2 years of age. Cytokine analyses of responses to housedust-mite
      allergen used ELISA and reverse-transcriptase PCR. We also measured responses to
      Fel d1 (cat allergen) and tetanus toxoid. FINDINGS: Samples from 18 atopic and 13
      non-atopic infants showed low-level Th2-skewed allergen-specific responses at
      birth, with little accompanying specific interferon-gamma production. Neonatal
      Th2 responses were lower in the atopic group than in the non-atopic group; the
      differences were significant for interleukin-4 (mRNA: beta-actin ratio 0.48 [SE
      0.15] vs 0.15 [0.06], p=0.049), interleukin-6 (4750 [48] vs 1352 [51] pg/mL
      culture fluid, p=0.003), interleukin-10 (1162 [228] vs 485 [89], p=0.015), and
      interleukin-13 (7.1 [0.9] vs 0.9 [0.3], p=0.008). There was rapid suppression of
      Th2 responses during the first year of life in non-atopic children, but there was
      consolidation of responses in atopic children, associated with defective neonatal
      interferon-gamma production. INTERPRETATION: The continuation of fetal allergen
      specific Th2 responses during infancy is a defining feature of the inductive
      phase of atopic disease, and is associated with decreased capacity for production
      of the Th1 cytokine interferon y by atopic neonates. These findings provide a
      plausible mechanism for persistence of the fetal Th2 responses during early
      childhood in atopic individuals and subsequent expression of disease.

PMID- 9923876
TI  - Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1
      infected patients treated with highly active antiretroviral therapy.
AB  - BACKGROUND: Prophylactic drugs for Pneumocystis carinii pneumonia (PCP) are
      strongly recommended for HIV-1-infected patients with CD4 cell counts of less
      than 200 cells/microL. Because of the highly active antiretroviral therapy
      (HAART) currently available, we speculated that prophylaxis can be discontinued
      in patients with CD4 cell counts of more than 200 cells/microL. METHODS: In this
      prospective observational study, PCP prophylaxis (primary or secondary) was
      discontinued in HIV-1-infected patients whose CD4 cell count had increased above
      200 cells/microL (documented twice with an interval of at least 1 month) as a
      result of HAART. Patients and their CD4 cell counts were monitored every 3
      months. The primary endpoint of the study was the occurrence or reoccurrence of
      PCP. FINDINGS: 78 patients were enrolled: 62 patients were receiving prophylaxis
      for primary prevention of PCP and 16 patients for secondary prevention of PCP. At
      the time of discontinuation of prophylaxis, the mean CD4 cell count was 347
      cells/microL, and HIV-1-RNA was not detectable in 61 patients. The lowest mean
      CD4 cell count during prophylaxis was 79 cells/microL. Patients stopped
      prophylaxis 9.8 (SD 6.4) months after they started HAART. The mean follow-up
      after discontinuation of prophylaxis was 12.7 (SD 7.6) months, and none of the
      patients developed PCP (97.5% one-sided CI 0-4.4%). INTERPRETATION: The
      preliminary results of this study indicate that PCP prophylaxis can be stopped
      safely in HIV-1-infected patients whose CD4 cell counts have increased above 200
      cells/microL after treatment with HAART.

PMID- 9923877
TI  - Dementia and snoring.

PMID- 9923878
TI  - A brief clinical instrument to classify frailty in elderly people.

PMID- 9923879
TI  - Developing teeth as biomarker of dioxin exposure.

PMID- 9923880
TI  - Sex ratio after exposure to dioxin-like chemicals in Taiwan.

PMID- 9923881
TI  - Dobrava hantavirus in Russia.

PMID- 9923882
TI  - Imported melioidosis in England and Wales.

PMID- 9923883
TI  - Implications of age-based policies for influenza immunisation.

PMID- 9923884
TI  - Risk of breast cancer in offspring of male breast-cancer patients.

PMID- 9923885
TI  - Lipid-lowering drugs and homocysteine.

PMID- 9923886
TI  - Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic
      cholestasis of pregnancy.

PMID- 9923887
TI  - Monitoring HIV-1 treatment in immune-cell subsets with ultrasensitive
      fluorescence-in-situ hybridisation.

PMID- 9923888
TI  - Motor cortex stimulation for phantom limb pain.

PMID- 9923889
TI  - New treatments for alcohol dependency better than old.

PMID- 9923890
TI  - Michael Smith: working to stop Canada's brain drain.

PMID- 9923891
TI  - Prevention better than cure?

PMID- 9923892
TI  - Huge percentage of women volunteer for zidovudine project.

PMID- 9923894
TI  - Platelet GPIIb-IIIa blockers.
AB  - Regardless of the event that stimulates the aggregation of platelets, the
      receptor alpha(IIb)beta3--one of a family of adhesion receptors known as
      integrins--has a key role in the process. The past decade has seen the
      publication of 10 phase III (randomised) clinical trials of four members of a new
      class of antiplatelet drugs, the GPIIb-IIIa blockers, targeted at this important
      receptor. Three (abciximab, eptifibatide, and tirofiban) are licensed for human
      use. 10 other GbIIb-IIIa blockers are in phase II or III human studies. In all 10
      placebo-controlled trials, done in the clinical settings of percutaneous coronary
      intervention or acute coronary syndrome in patients on aspirin, the endpoints
      favoured the active drug, with a risk reduction for death or non-fatal myocardial
      infarction of about 21% overall. With attention to heparin dose the risk of
      bleeding is not a major concern with these agents. The GPIIb-IIIa blockers are
      taking the clinician and patient out of the era of aspirin monotherapy when
      platelet inhibition is required.

PMID- 9923893
TI  - Role of maintenance treatment in opioid dependence.
AB  - Methadone maintenance treatment (MMT) involves the daily administration of the
      oral opioid agonist methadone as a treatment for opioid dependence-a persistent
      disorder with a substantial risk of premature death. MMT improves health and
      reduces illicit heroin use, infectious-disease transmission, and overdose death.
      However, its effectiveness is compromised if low maintenance doses of methadone
      (<60 mg) are used and patients are pressured to become prematurely abstinent from
      methadone. Pregnancy and psychiatric comorbidity are not contraindications for
      MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone,
      buprenorphine) may increase patient choice and avoid some of the more unpleasant
      aspects of MMT. The public-health challenge for the future is to develop and
      continue to deliver safe and effective forms of opioid maintenance treatment to
      as many opioid-dependent individuals as can benefit from them.

PMID- 9923895
TI  - Politics, power, and pediatrics.

PMID- 9923896
TI  - Prevention of dementia: Syst-Eur trial.

PMID- 9923897
TI  - Prevention of dementia: Syst-Eur trial.

PMID- 9923898
TI  - Prevention of dementia: Syst-Eur trial.

PMID- 9923899
TI  - Treatment of trichuris infection with albendazole.

PMID- 9923900
TI  - Treatment of trichuris infection with albendazole.

PMID- 9923901
TI  - Paraffin and body-packers.

PMID- 9923902
TI  - Paraffin and body-packers.

PMID- 9923903
TI  - Interleukin-6 concentrations in neonatal sepsis.

PMID- 9923904
TI  - Socioeconomic status and bowel cancer.

PMID- 9923905
TI  - Reversible Huntington's disease--lesion to the globus pallidus?

PMID- 9923906
TI  - HIV vaccine: how long must we wait?

PMID- 9923907
TI  - HIV vaccine: how long must we wait?

PMID- 9923909
TI  - Antibiotic resistance in Helicobacter pylori.

PMID- 9923908
TI  - Antibiotic resistance in Helicobacter pylori.

PMID- 9923910
TI  - Psychiatrists' attitudes to euthanasia.

PMID- 9923911
TI  - Psychiatrists' attitudes to euthanasia.

PMID- 9923912
TI  - Drop-outs in tamoxifen prevention trials.

PMID- 9923915
TI  - Picturing the brain on the web.

PMID- 9923913
TI  - Catalytic converters and prevention of suicides.

PMID- 9923916
TI  - The Nobel chronicles. 1934: George Hoyt Whipple (1878-1976); George Richard Minot
      (1885-1950); William Perry Murphy (1892-1987).

PMID- 9923917
TI  - Sketches from The Lancet. Smoking.

PMID- 9923918
TI  - Whither human pathology?

PMID- 9923919
TI  - Recommendations for the reporting of soft tissue sarcomas. Association of
      Directors of Anatomic and Surgical Pathology.

PMID- 9923920
TI  - A germline hMSH2 alteration is unrelated to colonic microsatellite instability in
      patients with ulcerative colitis.
AB  - Recently, a polymorphism in the hMSH2 DNA mismatch repair gene has been
      associated with the development of dysplasia in ulcerative colitis (UC) patients.
      This polymorphism is of interest because DNA mismatch repair defects result in
      alterations in microsatellite stability. The current study was designed to
      determine whether this hMSH2 polymorphism associates with the development of
      microsatellite instability and dysplasia in UC patients. The hMSH2 genotype of 96
      UC patients was determined by direct DNA sequencing. In addition, we examined 363
      samples of colonic mucosa from 93 of these UC patients for microsatellite
      mutation by polymerase chain reaction (PCR) at eight loci. Three cases had
      insufficient DNA for microsatellite instability studies. The hMSH2 polymorphism
      was identified in 13 of the 96 patients examined (13.5%). The polymorphism was
      observed in 7 of 46 patients with dysplasia (15.2%), and in 6 of 50 patients
      without dysplasia (12.0%). Microsatellite instability was identified in 35 tissue
      samples (25 regenerative, one indefinite for dysplasia, eight dysplasias, and one
      invasive carcinoma) from 26 patients. Two patients with microsatellite
      instability had the hMSH2 alteration. The 11 remaining patients had the hMSH2
      polymorphism, but no evidence of microsatellite mutations with any of the markers
      tested. We were unable to confirm the previously reported findings that the
      specific germline hMSH2 alteration represents a marker for increased risk of
      dysplasia in patients with UC, nor is it responsible for the development of
      microsatellite instability in these patients.

PMID- 9923921
TI  - Morphological features of the human umbilical vein in normal, sickle cell trait,
      and sickle cell disease pregnancies.
AB  - Pathological changes often occur in the placenta of women with sickle cell
      disease (SCD). These alterations are caused by sickling of erythrocytes and
      vasoocclusion in the placental circulation, leading to regional hypoxia. However,
      the morphological status of the umbilical cord, which is in close physical
      association with the placenta, is not documented under such conditions. To
      explore this, the umbilical vein structure in healthy, sickle cell trait (the
      heterozygous state), and SCD pregnancies was studied using scanning (SEM) and
      transmission electron microscopy (TEM). Interestingly, the sickle cell trait
      umbilical vein architecture was morphologically similar to that in control veins,
      whereas numerous alterations were seen in the SCD umbilical vein wall. In SEM,
      the SCD umbilical vein endothelial cells showed atypical morphologies. TEM
      analysis of the tunica media showed (1) smooth muscle cell proliferation and
      increase in the thickness of the basement membrane underlying the cells; (2)
      areas of necrosis; (3) reduplication of the inner elastic lamina. Such features
      were often seen in sickle patients vasculature at autopsy. Our findings could
      have importance because tissue hypoxemia is an integral part of vasoocclusion. We
      conclude that the SCD umbilical vein may be an additional tool for studying
      vasoocclusion in sickle cell disease.

PMID- 9923922
TI  - Gallbladder adenomas have molecular abnormalities different from those present in
      gallbladder carcinomas.
AB  - Although most gallbladder carcinomas evolve from dysplasia and carcinoma in situ,
      the role of gallbladder adenomas in the pathogenesis of gallbladder carcinoma is
      still controversial. A series of molecular changes including loss of
      heterozygosity (LOH) at 17p (TP53 gene), 13q (RB gene), 18q (DCC gene), and 9p21
      (CDKN2a gene) chromosomal regions have been identified in dysplasias, carcinomas
      in situ, and invasive carcinomas of the gallbladder, whereas mutations in K- and
      N-ras genes are rare. To determine whether the molecular abnormalities of
      adenomas are similar to those found in carcinomas, we obtained extracted DNA from
      precisely microdissected tissue from 16 gallbladder adenomas (14 pyloric and 2
      intestinal-type). We determined the presence of mutations in TP53, K- and N-ras
      genes, and LOH at five chromosomal regions (5q22 APC-MCC region, RB, TP53, DCC
      and 9p21-CDKN2a). For the TP53 mutation study, single strand conformational
      polymorphism (SSCP) analysis in exons 4 to 8 were performed. K- and N-ras
      mutations detection was performed by designed restriction fragment length
      polymorphism (RFLP) method and sequencing. Only a single LOH (at 5q22) was
      detected in a gallbladder adenoma of intestinal type. No mutations at the TP53
      were detected. Four adenomas (25%) showed K-ras mutations (two in codon 12 and
      two in codon 61). We conclude that gallbladder adenoma lacks the molecular
      changes frequently detected in dysplasia, carcinoma in situ, and invasive
      carcinoma of the gallbladder. Likewise the occurrence of K-ras mutations at codon
      12 and 61 in 25% of adenomas strongly suggests that these lesions are not
      precursors of invasive gallbladder carcinoma.

PMID- 9923923
TI  - Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.
AB  - Placental trophoblasts are the primary source of serum inhibin during pregnancy.
      We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and
      compare the results with those for established markers of trophoblastic
      differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term
      placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three
      gestational, one testicular, one mediastinal), and five placental site
      trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha
      subunit of inhibin, hPL, and beta-hCG. Additionally, six first-trimester
      placentas were immunolabeled with antibody to inhibin alone. Trophoblastic
      subpopulations were assessed for the number of positive cells (1% to 24% = 1+,25%
      to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta
      and HM was similar, because beta-hCG was the most sensitive marker (4+) of
      syncytiotrophoblasts followed by inhibin (3-4+) and hPL (2-3+). Immunolabeling of
      syncytiotrophoblasts in CC was similar to that in term placenta and HM, except
      for negative hPL staining in two cases. In HM, inhibin labeling of intermediate
      trophoblasts (2-3+) was less than that for hPL (3-4+). In CC, inhibin and hPL
      labeling of intermediate trophoblasts was more variable with negative hPL
      reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT,
      inhibin immunolabeling was a better marker than hPL in two cases, inferior in
      two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than
      that for beta-hCG, but did not have the often marked background staining that was
      present with beta-hCG. Immunolabeling of trophoblast subpopulations for inhibin
      was similar between first-trimester placenta, term placenta, and HM. We conclude
      that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia
      and should be included in the antibody panel with beta-hCG and hPL.

PMID- 9923924
TI  - Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: a
      study of 28 cases.
AB  - Extraskeletal osteosarcoma (EOSA), a rare malignant soft tissue tumor, is by
      definition unattached to the skeleton and composed of malignant cells of
      osteoblastic phenotype which produce osseous matrix (ie, neoplastic bone).
      Because of its location, it can mimic other soft tissue tumors, and its matrix
      can be mistaken for hyalinized collagen. Antiosteocalcin (OC) and antiosteonectin
      (ON), antibodies against two abundant human bone proteins, are explored in the
      diagnosis of EOSA. Twenty-eight cases coded as EOSA (n=24) or probable EOSA (n =
      4) were identified from the Soft Tissue Registry of the Armed Forces Institute of
      Pathology (Washington DC). All cases had paraffin blocks available for
      immunohistochemistry. OC and ON (Biodesign International, Kennebunk, ME, clones
      OC1 and OST1) immunostaining for tumor cells and matrix was graded on a four
      tiered grading system: 1 = focal (< 50%) weak staining; 2 = focal strong
      staining; 3 = diffuse (> or = 50%) weak staining; and 4 = diffuse strong
      staining. Patient ages ranged from 9 to 80 years, with a mean age of 57 years.
      There were 9 female patients and 19 male patients. The tumor sizes ranged from
      1.5 to 15 centimeters, with a mean size of 5.8 centimeters. Locations included
      the lower extremity (n=14), trunk (n=9), upper extremity (n=4), and head and neck
      (n=1). Subtypes included 12 osteoblastic, 4 fibroblastic, 2 chondroblastic, 2
      well differentiated, 1 telangiectatic, 1 small cell, and 6 giant cell rich EOSAs;
      the latter resembled giant cell rich malignant fibrous histiocytomas with
      neoplastic bone formation. All tumors had both neoplastic cells and bony tumor
      matrix to evaluate. OC was 82% sensitive for EOSA neoplastic cells (1 to 4+),
      with immunostaining of neoplastic cells away from bone in 91% of cases, and 75%
      for bony tumor matrix (2 to 4+). ON was 93% sensitive for EOSA neoplastic cells
      (2 to 4+), yet only 39% for bony tumor matrix (1 to 4+). In 100% giant cell rich
      EOSA, neoplastic cells were positive for OC and ON (2 to 4+). OC showed 100%
      specificity for osteoblasts as it was nonreactive in all nonbone cells. ON was
      not specific for osteoblasts but consistently immunostained other cell types in
      our EOSA tumors: fibroblasts (100%), pericytes (96%), endothelial cells (92%),
      chondrocytes (5/5), basal layer of skin epithelium (1/4), nerves (2/2), and
      osteoclastic giant cells (64%). ON also stained several other cell types in
      normal and neoplastic tissues in our battery of preliminary stainings; OC was
      negative in all nonosteoblastic tissues and tumors. Both OC and ON were specific
      for osteoid matrix as they were nonreactive in both collagen and cartilage
      matrix. OC is a sensitive and specific marker for bone cells and would be helpful
      in identifying EOSA, even in the absence of neoplastic bone on small biopsies. ON
      and OC (more sensitive) will both distinguish malignant bone from collagen and
      cartilage matrix, essential to the diagnosis of EOSA.

PMID- 9923925
TI  - Fibrosis/cirrhosis after orthotopic liver transplantation.
AB  - The causes and pathologic changes leading to fibrosis and cirrhosis after
      orthotopic liver transplantation (OLT) are not fully defined. The computerized
      pathology files were searched for cases of fibrosis/cirrhosis after OLT. Of 493
      grafts from 435 patients, 35 grafts from 32 patients of posttransplantation liver
      fibrosis/cirrhosis were identified and retrieved (7%). Detailed histopathologic
      examinations of all post-OLT liver biopsy specimens were performed in conjunction
      with clinical, virologic, serologic, and molecular diagnostics information. Two
      cases with subcapsular septa and fibrous tissue close to hilum were excluded as
      false positives. Fibrosis/cirrhosis was confirmed in the remaining 33 grafts. In
      20, the underlying cause was recurrent viral hepatitis, including eight with
      hepatitis C, 10 with hepatitis B, and two with combined hepatitis C and B.
      Another two with pretransplantation chronic hepatitis B developed cirrhosis
      without detectable virologic markers after OLT; these were biliary type secondary
      to obstruction in one, and chronic changes due to severe graft ischemia in one.
      Three patients acquired hepatitis C after OLT, with molecular confirmation
      available in two. In five patients, the underlying causes were Budd-Chiari
      syndrome and autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent
      primary biliary cirrhosis, alcohol-induced liver disease, and recurrent bile duct
      carcinoma. Three cases had centrilobular fibrosis but without bridging septa or
      cirrhosis as a result of chronic rejection. It was concluded that (1) Cirrhosis
      after OLT is uncommon (7%). (2) Chronic rejection does not lead to cirrhosis, but
      it may result in centrilobular fibrosis. (3) In most (70%) cases, cirrhosis after
      OLT is attributed to recurrent or acquired viral hepatitis.

PMID- 9923926
TI  - Peripheral T and putative natural killer cell lymphomas commonly coexpress CD95
      and CD95 ligand.
AB  - The CD95 (Fas)/CD95 ligand (CD95L) system is an important mechanism triggering
      apoptosis, and CD95L expression has recently been implicated for immune evasion
      and aggressive behavior in malignancies. This study aimed to investigate CD95 and
      CD95L expression in lymphomas and the possible relationship with tumor cell
      apoptosis, with emphasis on the natural killer (NK) cell lymphomas, which are
      highly aggressive neoplasms and frequently exhibit tumor cell apoptosis/necrosis.
      Frozen sections of 82 cases of lymphomas obtained from Queen Elizabeth Hospital
      and Caritas Medical Center, Hong Kong, were immunostained with polyclonal anti
      CD95 and anti-CD95L antibodies. The NK-cell lymphomas were also studied for
      apoptosis by in situ end labeling (ISEL) method, and zonal tumor cell death was
      evaluated semiquantitatively. The cases studied included 27 NK-, 22 T-, and 33 B
      cell lymphomas. CD95 was expressed in 25 (93%) NK-, 11 (50%) T-, and 14 (42%) B
      cell lymphomas. CD95L was expressed in 19 (70%) NK-, 15 (68%) T-, and 3 (9%) B
      cell lymphomas. There was significant difference in the frequency of CD95
      expression between B- and NK- (P < .001), and between T- and NK-cell lymphomas (P
      < .05), and in CD95L expression between B- and T- (P < .01) or NK-cell (P < .01)
      lymphomas. Zonal tumor cell death was present in 21 (78%) NK-cell lymphomas and 1
      (4.5%) T-cell lymphoma and showed no correlation with CD95 or CD95L expression.
      ISEL analysis showed apoptosis predominantly in the viable areas in only 5 (24%)
      NK-cell lymphomas. In conclusion, CD95L is frequently expressed in NK- and T-cell
      lymphomas, but rarely in B-cell lymphomas. Zonal tumor cell death is not
      correlated with CD95 or CD95L expression and thus the CD95/CD95L system probably
      does not contribute significantly to this phenomenon. We postulate that the
      frequent expression of CD95L by NK- and T-cell lymphomas may mediate local or
      systemic tissue damage and immune evasion, and may contribute to the clinical
      aggressiveness of these tumors.

PMID- 9923927
TI  - In situ hybridization: a molecular approach for the diagnosis of the
      microsporidian parasite Enterocytozoon bieneusi.
AB  - Microsporidia are emerging as opportunistic pathogens in patients with acquired
      immunodeficiency syndrome (AIDS). Enterocytozoon bieneusi is the most commonly
      reported microsporidium that is detected in gastrointestinal specimens. This
      report describes an in situ hybridization technique with a 30-base specific
      synthetic DNA probe for detection of E bieneusi by light microscopy. Formalin
      fixed paraffin-embedded duodenal biopsy specimens from three patients with AIDS,
      chronic diarrhea, and E bieneusi infection confirmed by electron microscopy were
      used in this study. Light microscopic examination after colorimetric detection
      allowed the identification of different stages of the pathogen's life cycle in
      the cytoplasm of enterocytes. No cross-reactivity was noted between the probe and
      human DNA. Our study underscores the applicability of a synthetic-labeled
      oligonucleotide for the detection and identification of E bieneusi in clinical
      samples.

PMID- 9923928
TI  - Chronic recurrent multifocal osteomyelitis in children: diagnostic value of
      histopathology and microbial testing.
AB  - Chronic recurrent, unifocal or multifocal osteomyelitis (CRMO), an inflammatory
      disorder of unknown origin, involves different osseous sites and may be
      associated with palmoplantar pustulosis. Bacterial cultures of affected tissue
      were reported negative in nearly all cases. Radiological and magnetic resonance
      imaging features of CRMO have been described, but differential diagnosis remains
      difficult, including rheumatic diseases, bacterial osteomyelitis, and malignancy.
      Although definite diagnosis relies on histopathologic confirmation by biopsy,
      histopathologic criteria have not been defined. Because CRMO may be treated with
      nonsteroidal antiinflammatory drugs, but not antibiotics, distinguishing CRMO
      from bacterial osteomyelitis is of major importance. Histopathologic analysis of
      12 patients with CRMO indicated a wide variation of reparative changes of bone,
      but chronic inflammation could not be found at all sites in the same biopsy. The
      inflammatory infiltrate was mostly scattered, consisting mainly of lymphocytes,
      plasma cells, histiocytes, and also few neutrophil granulocytes.
      Immunohistochemistry showed a predominance of CD3(+), CD45RO(+) T-cells, which
      were mainly CD8(+). In addition, CD20(+) B cells and CD68(+) macrophages were
      abundant in each biopsy specimen. Mild lymphocytic and granulocytic infiltrates
      were also detected in three synovial biopsy specimens obtained from adjacent
      joints. All bacterial and fungal cultures from native biopsy tissues were
      negative. Amplification of partial-length 16S ribosomal DNA by polymerase chain
      reaction (PCR) using broad-range eubacterial primers was below the detection
      limit in all patients. Because histopathologic features alone may not provide
      conclusive evidence, CRMO should be included in the differential diagnosis of
      chronic inflammatory bone lesions in children, and the definite diagnosis should
      be made by the clinical picture, x-ray studies, bone scan, bacterial culture, and
      histopathologic analysis in a multidisciplinary approach.

PMID- 9923929
TI  - Aberrant crypt foci in patients with neoplastic and nonneoplastic colonic
      disease.
AB  - Aberrant crypt foci (ACF) are putative preneoplastic lesions that might represent
      the earliest morphological lesion visible in colonic carcinogenesis. However,
      findings concerning the growth and morphological features of these lesions in
      human studies suggest that ACF are highly heterogeneous in nature. In this study,
      we evaluated the morphological features of a large number of ACF in colon mucosa
      of 26 patients with colorectal carcinoma (CRC), four patients with adenoma as
      well as seven patients with nonneoplastic colonic diseases. By dissecting
      microscope, 508 ACF were identified, and of these, 378 were sampled for
      histological examination. The median ACF density (number of ACF/cm2) was
      significantly higher in the left colon than in the right colon (0.047 v 0.014
      ACF/cm2). Unexpectedly, in our series, the overall ACF density was higher in the
      nonneoplastic colonic diseases than in CRC (0.13 v 0.032 ACF/cm2, P=.0087), cases
      of nonneoplastic diseases, however, being limited to 7 patients. ACF were
      significantly larger in colons with CRC or adenoma than in colons with
      nonneoplastic disease (P < .03). On histological examination, we observed 133 ACF
      with normal epithelium, 189 ACF with hyperplasia, 27 ACF with atypical
      hyperplasia, and 29 ACF with dysplasia. We noted a progressive increase of median
      ACF size from normal mucosa to hyperplasia, atypical hyperplasia, and dysplasia.
      Dysplastic ACF were more frequently observed in patients with CRC or adenoma and
      showed predominantly elongated crypt orifices (P < .0001). We conclude that ACF
      are histologically heterogeneous, encompass a spectrum of lesions of which only a
      subset are associated with dysplasia and then represent an early step in
      colorectal carcinogenesis. ACF with dysplasia are characterized by larger size,
      elongated crypt orifices, and an association with CRC.

PMID- 9923930
TI  - Evaluation of gastric mucosal biopsy site and number for identification of
      Helicobacter pylori or intestinal metaplasia: role of the Sydney System.
AB  - Pathologists are frequently asked to evaluate gastric mucosal biopsy specimens
      for the presence of Helicobacter pylori infection and for potentially important
      changes such as intestinal metaplasia. No agreed-on system is both available and
      prospectively shown to provide reliable estimates of the underlying pathological
      condition. The Sydney System combined topographical, morphological, and causative
      information for evaluation of gastric biopsy specimens and provided
      recommendations regarding biopsy site and number. Both the biopsy sites and
      number were changed in 1994. Gastric biopsy specimens from patients who had
      multiple biopsies performed on predetermined sites were examined to compare the
      original and the revised Sydney Systems for the detection of intestinal
      metaplasia and H pylori. The diagnosis based on both versions of the Sydney
      System was then compared with that obtained by evaluating all specimens. Forty
      six patients were studied, 20 with H pylori infection and 36 with intestinal
      metaplasia. Using either version of the Sydney System correctly categorized H
      pylori infection status in 100%. Both the original and the revised Sydney
      recommendations seriously underestimated the prevalence of intestinal metaplasia.
      Intestinal metaplasia was missed in more than 50% of those with confirmed
      intestinal metaplasia. No set or site of biopsy specimens was found that could
      reliably exclude the presence of intestinal metaplasia. Current and future
      studies that use the Sydney System as basis for detecting intestinal metaplasia
      are not likely to be reliable. Likewise, using the Sydney System to test
      posttherapy or with time will not accurately reflect the true status of
      intestinal metaplasia.

PMID- 9923931
TI  - Sensitive detection of rare Ewing's sarcoma cells in peripheral blood by reverse
      transcriptase polymerase chain reaction.
AB  - Disseminated disease is very important in the clinical assessment of pediatric
      sarcomas. Several reports suggest that reverse transcriptase polymerase chain
      reaction (RT-PCR) holds great promise in the early staging of cancer patients in
      general. However, the complexities of these protocols hamper adequate
      standardization, and their application as routine diagnostic tools has been
      difficult. The aim of this study is to assess the actual minimal number of tumor
      cells that may be detected by RT-PCR in a blood sample. Specific tumor cell
      dilutions from a Ewing's sarcoma cell line reconstituted in peripheral blood from
      healthy individuals were "ficolled" and submitted to RNA extraction for cDNA
      preparation and PCR amplification of the t(11-22) (q24;q12) fusion transcript.
      After PCR amplification, we were able to detect the EWS/FI-1 chimeric gene
      product at a dilution of 10 tumor cells per 1 or 2 mL of blood. Our simple method
      supports a role for routine clinical use of RT-PCR in the detection of
      circulating Ewing's sarcoma cells.

PMID- 9923932
TI  - Polysomies but not Y chromosome losses have prognostic significance in pTa/pT1
      urinary bladder cancer.
AB  - A disturbed cellular DNA content is of potential diagnostic and prognostic
      relevance in urinary bladder cancer. To evaluate the prognostic significance of
      individual chromosomal aberrations in superficial bladder cancer, specimens of
      105 tumors (67 pTa, 38 pT1) were examined by fluorescence in situ hybridization
      (FISH). FISH allows quantitation of chromosomes on a cell by cell level.
      Centromere probes for the chromosomes Y, 1, and 17 were used. There was a strong
      association between polysomies of the chromosomes 1 (found in 46% of tumors) and
      17 (40% of tumors, P < .0001). Polysomies (1 and 17) were significantly more
      frequent in pT1 than in pTa tumors (P < .0001 each). In pTa tumors, polysomies of
      both chromosomes were linked to a high risk of recurrences; polysomy 17 was
      associated with an increased risk of progression (P < .05 each). There was no
      significant association between polysomies and an unfavorable prognosis in pT1
      carcinomas. Previous studies had suggested a prognostic role of Y losses in
      bladder cancer. However, Y losses were not linked to recurrences or tumor
      progression in pTa or pT1 tumors of 67 male patients. These data show that marked
      genetic differences exist between pTa and pT1 carcinomas. They also indicate that
      polysomies of different chromosomes may have prognostic relevance in pTa urinary
      bladder cancer.

PMID- 9923933
TI  - Cranial and extracranial fasciitis of childhood: a clinicopathologic and
      immunohistochemical study.
AB  - Fasciitis of various types constitutes a distinctive category of soft tissue
      lesions whose microscopic features are known for their potential to evoke a
      pathological diagnosis of one or another type of sarcoma. Nodular fasciitis is
      the archetype of this group of "fibrous tumors." Cranial fasciitis is considered
      a nonneoplastic lesion similar to nodular fasciitis, which is seen almost
      exclusively in infants and children and has unique clinicopathologic features.
      The current study documents our experience with fibrous-myofibroblastic
      proliferations in extracranial sites, mainly in the head and neck region of young
      children, whose histological features resemble those of cranial fasciitis. These
      lesions were composed of loosely arranged spindle to stellate cells in a myxoid
      background. One patient in the study had both cranial and extracranial
      involvement. Some histological overlap between nodular fasciitis and cranial
      extracranial fasciitis was noted, but the latter lesion tended to be more uniform
      in appearance than nodular fasciitis with its fascicular, spindle cell features
      and variability in histological patterns within the same lesion, unlike the more
      consistently uniform myxoid appearance of the cranial and extracranial lesions.
      Immunohistochemically, the spindle cells of the extracranial lesions and the one
      case of cranial fasciitis co-expressed vimentin and smooth muscle actin. The
      extracranial lesions had a predilection for children in the first year of life
      with all cases occurring at or before 2 years of age, unlike nodular fasciitis,
      which is rarely seen in the first 4 to 5 years of life. The cranial and
      extracranial fasciitides should be differentiated from the fibromatoses that tend
      to locally recur, unlike the nonrecurring behavior of these lesions in common
      with the other types of fasciitis.

PMID- 9923934
TI  - Prevalence of developmental and inflammatory lesions in nonmolar first-trimester
      spontaneous abortions.
AB  - The management of patients with first-trimester spontaneous abortions is
      handicapped by two problems: difficulty in recognizing conceptions that abort
      because of abnormal karyotypes and an incomplete understanding of what causes
      abortions with normal karyotypes. Our goals in this study were to define features
      useful in distinguishing normal from abnormal karyotype and to identify
      pathological processes contributing to abortions with a normal karyotype. The
      study population consisted of 668 well-characterized first-trimester spontaneous
      abortions derived from a larger study of 1,054 consecutively karyotyped
      spontaneous abortions. Clinical factors increased in specimens with normal
      karyotype were maternal age younger than 20 years (P=.0003) and autoimmune
      markers (P=.0474). Developmental features associated with abnormal karyotype were
      developmental stage less than 6 weeks (P=.0017), hydropic villi greater than 1 mm
      (P=.0004), and villi with two or more dysmorphic features (P=.0001).
      Developmental stage greater than 11.5 weeks was increased with normal karyotype
      (P=.0001). Histological features increased in specimens with a normal karyotype
      were chronic intervillositis (P=.0003), increased perivillous fibrin deposition
      with intermediate trophoblast (P=.0006), decidual plasma cells (P=.0040),
      deciduitis without plasma cells (P=.0660), and chronic villitis (P=.1581).
      Overall, 19% of samples with a normal karyotype versus 8% with abnormal karyotype
      had one or more of these findings (P < .0001). Autoimmune markers, chronic
      intervillositis, and increased perivillous fibrin with intermediate trophoblast
      all had positive predictive values greater than 85% for normal karyotype, whereas
      dysmorphic villi had a positive predictive value of 90% for abnormal karyotype.
      Patients with recurrent spontaneous abortion and normal karyotype were more
      likely to have one or more of the histological features listed above (31%) than
      patients with normal karyotype and no prior abortions (13%) and patients with
      recurrent abortion and abnormal karyotype (11%).

PMID- 9923935
TI  - Central hyalinizing clear cell carcinoma of the mandible and the maxilla a
      clinicopathologic study of two cases with an analysis of the literature.
AB  - We describe two cases of primary intraosseous hyalinizing clear cell carcinomas
      of the jaws. One tumor arose in the mandible, the other in the maxilla. Both
      patients were adult women. Histologically, both tumors were characterized by a
      population of clear, glycogen-rich cells arranged in solid nests, trabeculae, and
      occasional single files, surrounded by a markedly hyalinized fibrous stroma. In
      close admixture with the clear cells, a second component of smaller cells having
      eosinophilic cytoplasms was also noted. Focal areas of squamous metaplasia were
      seen in one of the tumors. Neither nuclear pleomorphism nor mitotic activity were
      conspicuous features. Mucicarmine stains were negative in both tumors.
      Immunohistochemically, the tumor cells expressed cytokeratins and epithelial
      membrane antigen. Stains for S100 protein, smooth muscle specific actin, and
      carcinoembryonic antigen were all negative. Both patients are alive and well 14
      and 17 months respectively after the diagnosis without evidence of metastasis or
      recurrence. The major importance of recognizing the existence of this rare form
      of salivary gland-type adenocarcinoma arising as a primary lesion in the mandible
      or the maxilla lies in avoiding misdiagnosing it as other primary or metastatic
      clear cell neoplasms, including various odontogenic clear cell tumors, other
      primary intraosseous salivary gland tumors, and metastatic clear cell
      adenocarcinomas from other organs, particularly the kidney.

PMID- 9923936
TI  - Ectopic thyroid in the adrenal gland.
AB  - We report two cases of intraadrenal thyroid gland tissue, both found by abdominal
      computed tomography (CT) scan and ultrasound echography. Histologically, the
      lesions were composed of mature thyroid follicles, varying in size, and some with
      cystic dilatation. Immunohistochemical staining for thyroglobulin confirmed their
      thyroid follicular nature. In neither case was there any evidence of thyroid
      gland cancer or teratomatous elements. Clinical examinations, including CT,
      ultrasound echography, and scintscanning did not show any tumorous lesions in the
      thyroid gland or elsewhere. The cause of ectopic thyroid in the adrenal gland is
      not known. It seems difficult to explain these ectopic lesions on the basis of
      developmental error because their location is distant from the path of
      embryological descent of the thyroid. The most important practical consideration
      is that they must be distinguished from metastatic deposits from a clinical point
      of view.

PMID- 9923937
TI  - Microsatellite instability and gastric cancer subtypes.

PMID- 9923938
TI  - Human papillomavirus in spontaneous abortion.

PMID- 9923939
TI  - Prostatic adenocarcinoma with glomeruloid features.

PMID- 9923940
TI  - Athens Declaration for Healthy Cities.

PMID- 9923941
TI  - For debate: public health leadership--do we have it? Do we need it?

PMID- 9923942
TI  - The clinical epidemiology ward round: can we teach public health medicine at the
      bedside?
AB  - BACKGROUND: The clinical epidemiology ward round (CEWR) is an educational tool
      for integrating the teaching of epidemiology with clinical paediatrics. It aims
      to facilitate the acquisition of the knowledge, skills and attitudes that promote
      the effective application of epidemiological insights into routine clinical
      practice. This paper describes experience of the CEWR in a UK medical school and
      initial student responses to it. METHODS: Since 1995, the CEWR has formed an
      integral part of the clinical teaching given to all final phase medical students
      during their eight-week child health course at the University of Glasgow. It took
      place in a general paediatric ward of the Royal Hospital for Sick Children,
      Glasgow. Groups of up to seven students were taught by a clinical epidemiologist
      with a strong research interest, as well as clinical experience, in child health.
      Each round lasted approximately 90 minutes and the teaching style was informal
      and interactive. At the end of the child health course, students were asked a
      series of questions relating to the CEWR's educational objectives. RESULTS: The
      evaluation indicated that the CEWR had been well received by students, 85 per
      cent of whom said it was an excellent or good idea in principle, and 71 per cent
      of whom said it worked well in practice. Most students seemed unconvinced about
      its role in reinforcing epidemiological knowledge or in clinical skill
      development. CONCLUSION: The CEWR requires further development but offers a
      potentially inexpensive, effective and enjoyable vehicle for integrating the
      teaching of two previously separate components of the curriculum.

PMID- 9923943
TI  - A primary care perspective of meningococcal disease.
AB  - BACKGROUND: It is generally agreed that pre-admission benzyl penicillin improves
      the outcome in infection by Neisseria meningitidis. Even so, only a minority of
      cases in Birmingham received such treatment. The aim of this study was,
      therefore, to determine the views of general practitioners (GPs) in Birmingham on
      the early management of meningococcal disease, including the use of parenteral
      antibiotics. METHODS: A standard semi-structured confidential questionnaire was
      posted to GPs on the list of Birmingham Family Health Services Authority. The
      questions covered the GPs' clinical experience of meningococcal infection and
      their views on the pre-hospital management of suspected cases of Neisseria
      meningitidis. RESULTS: Completed questionnaires were received from 372 GPs, a
      response rate of 70 per cent. Nearly all GPs said they carried benzyl penicillin
      in their on-call bag (353; 95 per cent) and would give it to a patient they
      suspected had meningococcal disease (361; 97 per cent). A total of 208 GPs (56
      per cent) would not give parenteral chloramphenicol to a patient they suspected
      had meningococcal disease and a penicillin allergy, and only 25 (7 per cent)
      carried it as an alternative antibiotic. The most common reason for not giving
      chloramphenicol was unfamiliarity with dosages (132; 63.5 per cent). CONCLUSIONS:
      The vast majority of GPs in Birmingham would apparently give benzyl penicillin to
      a patient they suspected had meningococcal infection. No single issue emerged to
      explain why pre-admission administration of benzyl penicillin was so low. Further
      work is being carried out locally to help translate positive attitudes into a
      change in behaviour.

PMID- 9923944
TI  - Impact of infection on mortality and hospitalization in the North East of
      England.
AB  - BACKGROUND: Current modes of presentation of mortality and hospitalization data,
      based on codes in Chapter 1 of the International Classification of Diseases
      (ICD), hide the true importance of infection and other microbial diseases
      (infections). Our aim was to produce a new aggregation of ICD-9 to estimate their
      true impact. METHODS: ICD-9 codes for infections, irrespective of ICD-9 chapter,
      were extracted to form the new aggregation. We reanalysed routine mortality (1979
      1983 and 1989-1993) and hospital finished consultant episode data (FCEs) (1989
      1993) in the area of the former Northern Regional Health Authority (population
      approximately 3 million) using the new aggregation of codes. This area is in the
      North East of England. Age- and sex-specific rates of death and FCE from
      infection were calculated using mid-1981 and mid-1991 population estimates.
      RESULTS: Using ICD-9 Chapter 1 codes, 839 (0.4 per cent) deaths in 1989-1993 were
      classified as due to infection, compared with 12655 (6.7 per cent) with the new
      aggregation. In 1979-1983, 10.3 per cent of all deaths were due to infection. The
      highest rates of infection death were in the oldest age groups and infants. FCEs
      for infections were 1.2 per cent using ICD-9 Chapter 1 codes, but 5.4 per cent
      using the new aggregation. The highest rates of infection FCEs were in infants.
      Most infection deaths and hospitalizations were for respiratory disorders. Using
      the new aggregation, infection moved from the 13th ranking cause of death to the
      third ranking cause; and from the 15th ranking cause of hospitalization to the
      10th. CONCLUSIONS: The usual method of presenting data coded by ICD-9 chapters
      greatly understates the contribution of infection to morbidity and mortality and
      may mislead policy makers assessing the priority to be given to infections.

PMID- 9923945
TI  - Do women who undergo further investigation for breast screening suffer adverse
      psychological consequences? A multi-centre follow-up study comparing different
      breast screening result groups five months after their last breast screening
      appointment.
AB  - BACKGROUND: In 1995-1996 about 53500 women aged 50-64 attending for routine
      breast screening were called back for further investigation after an initial
      mammogram. Even when women were found to be clear after further investigation,
      significant adverse psychological consequences (PCs) can remain one month later.
      This follow-up study investigates whether residual emotional effects persisted
      five months after women received a clear result. METHODS: Women who had
      previously completed a questionnaire one month after their last breast screening
      appointment, at which they had a clear result, were invited to complete a further
      postal questionnaire four months later (five months after their last
      appointment). We compare women who received a clear result after assessment
      without fine needle aspiration cytology (FNAC), after assessment with FNAC, after
      a benign biopsy, and those who had been placed on early recall, with those who
      received a clear result after mammography (reference group). RESULTS: The
      response rate was 76 per cent (215/284). All groups of women who went on for
      further investigation suffered significantly greater adverse psychological
      consequences (PCs) at five months than women who were given a clear result after
      mammography. Compared with 10 per cent (5/52) of women who received a clear
      result after a basic mammogram, adverse psychological consequences were
      experienced by 59 per cent (27/46, p<0.00001) of the women who were placed on six
      month early recall, 61 per cent (14/23, p<0.0001) of women who had benign
      surgical biopsy, 44 per cent (18/41, p<0.0001) of women who received a clear
      result after assessment (with FNAC), and 45 per cent (23/51, p<0.0001) of women
      who received a clear result after assessment (without FNAC). Whereas all groups
      who had gone on for further investigations had experienced a significant decrease
      in PCs between one month and five months, those who were placed on six month
      early recall showed no significant difference in PCs between these two time
      periods. Other factors relating to adverse experiences as a result of breast
      screening are reported. CONCLUSION: Despite receiving a clear final result, women
      who undergo further investigation suffer significantly greater adverse
      psychological consequences five months after their last screening appointment
      than women who receive a clear result after mammography.

PMID- 9923946
TI  - Objectives of genetic counselling: differing views of purchasers, providers and
      users.
AB  - BACKGROUND: This study aimed to compare the views of purchasers, providers and
      users about the objectives of genetic counselling. METHODS: A modified Delphi
      technique was used, incorporating two postal questionnaires that were sent to six
      study groups with a three-month interval: purchasers (public health doctors (n =
      37) and regional advisers in general practice (n = 35)); providers (clinical
      geneticists (n = 33) and genetic counsellors (n = 25)); and users (out-patients
      (n = 36) and members of genetic support groups (n = 32)). The response rate for
      the first questionnaire was 115/198 (58 per cent) and for the second, 102/198 (52
      per cent). The first questionnaire asked an open-ended question about what the
      objectives of genetic counselling should be and asked respondents to rank order
      them. The second questionnaire summarized the views expressed in the first
      questionnaire and asked respondents to rank order the most frequently cited and
      most highly ranked five objectives. RESULTS: The five most frequently cited and
      highly ranked objectives from Questionnaire One were, in descending order:
      provide information, give support, facilitate decision-making, assess risk and
      achieve understanding. In response to Questionnaire Two, purchasers differed from
      providers and users in rating 'facilitate decision-making' more highly than did
      providers and users. By contrast, providers and users rated 'give information'
      more highly than did purchasers. CONCLUSIONS: Purchasers hold different views
      from providers and users about what the objectives of genetic counselling should
      be. This raises two questions: (1) Which views are or should be most influential
      in the future development of genetic counselling? (2) By what processes can more
      than one view on genetic counselling be integrated?

PMID- 9923947
TI  - The contracting round: achieving health gain or financial balance?
AB  - In the 1991 National Health Service reforms, health authorities became
      responsible for the health of their resident population, and they contract for
      health services from NHS providers - trusts and primary care services. A case
      study in Camden and Islington, an inner London health district, during 1996-1997
      shows that contracting was directed more towards achieving financial balance than
      health objectives. Reasons include the inflationary effect of competition within
      an internal market, the power of administrators in decision-making within the
      health authority, and lack of adequate financial accounting in the NHS to relate
      costs to health outcomes. The introduction of programme budgets for districts
      would provide more cost-effective use of the nation's resources.

PMID- 9923948
TI  - Quality indicators for general practice: which ones can general practitioners and
      health authority managers agree are important and how useful are they?
AB  - BACKGROUND: The aim of the study was to assess the face validity of quality
      indicators being proposed for use in general practice by health authorities.
      METHOD: A national survey of health authorities was carried out to identify
      quality indicators being proposed for use in general practice. A two-stage Delphi
      process was used to establish general practitioners' (GPs') and health authority
      managers' views on the face validity of identified indicators. A total of 240
      separate indicators identified by health authorities and the NHS Executive as
      potential markers of the quality of general practice care were assessed.
      Indicators related to access, organizational performance, preventive care, care
      for a small number of chronic diseases, prescribing and gatekeeping. The subjects
      were a purposive sample of 47 health authority managers and 57 general practice
      course organizers. RESULTS: Thirty-six indicators received median validity scores
      of 8 or 9 out of a maximum possible score of 9. Of this set, 83 per cent was
      rated identically by both groups of respondents. Prescribing and gatekeeping
      indicators generally received low validity scores. CONCLUSION: Acceptable face
      valid indicators were identified for all domains except gatekeeping. However, the
      indicators rated by the sample do not cover all aspects of care. No indicators
      were proposed for use by health authorities relating to effective communication,
      care of acute illness, health outcomes or patient evaluation. Although it is
      possible to develop indicators of general practice care which have face validity
      in the view of both GPs and managers, these will be very partial measures of
      quality. In the indicators used in this study, no explicit distinction was made
      between indicators designed to assess minimum standards with which all practices
      should comply, and indicators which could be used to reward higher levels of
      performance. Failure to separate these will result in antagonism from
      practitioners to quality improvement initiatives in the NHS, and a failure to
      engage the profession in improving quality of care.

PMID- 9923949
TI  - Episiotomy and perineal tears in low-risk UK primigravidae.
AB  - BACKGROUND: The aim of the study was to determine the rates and to describe the
      risk factors for episiotomy and perineal tears in low-risk primigravidae. METHOD:
      A cross-sectional survey of 101 randomly selected NHS hospitals in the UK was
      carried out between February 1993 and January 1994. Subjects were 40 consecutive
      low-risk primigravidae in each hospital. The main outcome measures were number
      and reasons for episiotomy, and number and degree of perineal tears. RESULTS: A
      large proportion of women (83 per cent) experienced some form of perineal trauma.
      Forty per cent of the women had an episiotomy only, 6 per cent an episiotomy and
      perineal tear, and 37 per cent perineal or other tears without episiotomy. The
      main reasons for performing an episiotomy were foetal distress (27 per cent),
      impending tear (25 per cent) and delay of the second stage of labour (21 per
      cent). Fifty-nine per cent of women with a delayed second stage had a spontaneous
      vaginal delivery and 41 per cent required instrumental assistance. The likelihood
      of having an episiotomy increased with the duration of the second stage of
      labour, irrespective of type of delivery. Episiotomy rates varied appreciably
      throughout regions and hospitals in the United Kingdom, ranging from 26 to 67 per
      cent. There was also a large regional variation in the rates of perineal trauma;
      generally, high rates of one outcome were associated with low rates of the other.
      Compared with white women, women from the Indian sub-continent were almost twice
      as likely and those from the Orient almost five times as likely to have an
      episiotomy. CONCLUSIONS: The magnitude of the geographical variation suggests a
      lack of uniformity in indications for performing episiotomies and that guidelines
      for performing episiotomies may need to be reviewed. The rates of episiotomy in
      women from the Indian sub-continent and Orient were very high compared with those
      for white women, and this requires clarification and explanation, as they are
      contrary to rates experienced in these ethnic groups in other countries.

PMID- 9923950
TI  - Occupation and risk of hip fracture.
AB  - BACKGROUND: Physical activity in old age probably protects against hip fracture.
      However, very little is known about the impact of occupation during working life,
      in terms of its physical activity level and the socio-economic status (SES) it
      indicates, on the risk of hip fracture in later life. METHOD: A population-based
      case-control study was conducted on 416 subjects to investigate relationships
      between risk of hip fracture and occupational physical activity and occupation
      related SES. Occupational physical activity was coded according to the proportion
      of the working day at ages 20 and 50 years that the subjects were likely to have
      spent sitting. The Australian Classification of Standard Occupations (ASCO) was
      used as the basis for the coding of SES, indicated by job titles. RESULTS:
      Compared with those in the intermediate category, women with a sedentary job at
      age 50 years (odds ratio (OR) 7.2, 95 per cent confidence interval (CI) 1.2-41.9)
      or a mainly weight-bearing job (OR 5.1, 95 per cent CI 1.1-23.2) had an increased
      risk of hip fracture. A decreasing hip fracture risk with increasing SES of the
      longest held job was also observed. CONCLUSION: The finding of a J-shaped
      relationship in women between occupational physical activity and risk of hip
      fracture supports the need for research into the most effective types of exercise
      for maintenance of bone strength. Furthermore, the protective effect of SES
      demonstrated in this study still need to be corroborated in other studies before
      establishing evidence of a causal relationship.

PMID- 9923951
TI  - Healthy housing--advice for students.

PMID- 9923952
TI  - Lowering blood pressure: a systematic review of sustained effects of non
      pharmacological interventions.
AB  - BACKGROUND: Risk factors for raised blood pressure include obesity, physical
      inactivity, high dietary salt intake, stress, and high alcohol consumption. Much
      less is known about the effects on blood pressure of modification of these risk
      factors for the purposes of disease prevention. A systematic review and meta
      analysis of randomized controlled trials (RCTs) was conducted to estimate the
      effects of various non-pharmacological interventions on blood pressure. METHODS:
      RCTs of single interventions aimed at altering these risk factors among adults
      aged 45 or older with and without hypertension, and with at least six months
      follow-up were included. MEDLINE was the primary source and the boundaries of the
      study were from 1966 to April 1995. RESULTS: The majority of RCTs were of short
      duration and did not provide guidance on the sustainability of effects and were
      excluded. Totals of eight RCTs of salt restriction, eight RCTs of weight
      reduction, eight of stress management, eight of exercise, and one of alcohol
      reduction of longer than six months duration were found. Net (i.e. intervention -
      control group) systolic blood pressure changes, mean mm Hg (with 95 per cent
      confidence intervals in parentheses), in hypertensives were as follows: salt
      restriction -2.9 (-5.8,0.0), weight loss -5.2 (-8.3,-2.0), stress control -1.0 (
      2.3,+0.3), and exercise -0.8 (-5.9,+4.2). Smaller changes were found in
      normotensive participants: salt restriction -1.3 (-2.7,+0.1), weight loss -2.8 (
      3.9,-1.8), exercise -0.2 (-2.8,+2.4), and alcohol reduction -2.1 (-4.1,-0.1).
      Some interventions (e.g. stress control in normotensives) were not examined in
      either hypertensives or normotensives. The majority of RCTs were of low
      methodological quality and bias often tended to increase the changes observed.
      Few of the trials controlled for the confounding effects of concurrent changes in
      other blood pressure risk factors. CONCLUSION: These net changes are probably
      overestimates of the effects that might be achieved by non-pharmacological
      interventions. There is a need for large-scale, long duration trials of these non
      pharmacological interventions in both hypertensive patients and normotensive
      people to determine effect sizes more accurately.

PMID- 9923953
TI  - Meeting women's need for a flexible abortion service: retrospective study of a
      specialist day-care unit.
AB  - BACKGROUND: Services for women seeking termination of pregnancy under the
      National Health Service have persistently failed to meet targets on accessibility
      and quality of care. A specialist day-care service was established in Lincoln in
      April 1993, taking referrals from general practitioners and family planning
      doctors via a dedicated telephone line and offering specialist counselling and
      the option of medical termination. The impact of this service was investigated in
      a retrospective study. METHODS: Women attending Lincoln County Hospital with an
      unwanted pregnancy between April 1991 and March 1996 were included. Demographic
      details and data on in-hospital care were obtained from the Patient
      Administration System; resident population data were obtained from routine
      sources; dates of last menstrual period and referral were obtained from samples
      of patient records and entries in ward diaries; patient satisfaction was assessed
      by questionnaire in a consecutive sample of 44 women. RESULTS: The number of
      terminations provided at Lincoln County Hospital increased from 24 to 40 per
      month at the time the service began. The proportion of the resident population's
      demand met by the local provider increased from 48 per cent to 83 per cent.
      Terminations before nine weeks increased from 24 per cent to 43 per cent; those
      beyond 12 weeks fell from 15 per cent to 7 per cent. Median gestational age at
      termination fell from 76 days to 60 days. Forty per cent of suitable women opted
      for medical termination. CONCLUSIONS: The new service was associated with a
      pronounced and sustained improvement in National Health Service termination of
      pregnancy. When offered the choice, many women opted for medical termination.

PMID- 9923954
TI  - The impact of obstetric risk factors and socioeconomic characteristics on
      utilization of antenatal care.
AB  - BACKGROUND: The objective of the study is to assess the impact of obstetric risk
      status and defined risk factors on utilization of antenatal care in a Swedish
      county. METHODS: An area-based, population study was carried out with
      retrospective review of standardized patient records before (n = 2008) and after
      (n = 1874) the introduction of a reduced schedule for surveillance of pregnancy.
      For assessment of individual risk factors a multiple regression model is used.
      RESULTS: Overall the number of contacts per pregnancy decreased from 13.2 to
      11.4. With the reduced routine programme the difference between low-risk and high
      risk women increased from 1.1 to 2.7 visits on average. In the multiple
      regression model socioeconomic characteristics had little influence on the use of
      antenatal care. Previous obstetric complications increased compliance to the
      schedule after the programme change. Complications during current pregnancy were
      important for the number of extra visits planned by the staff. Self referrals
      were most influenced by symptoms but in-patient care was influenced by multiple
      factors. The total explanatory ability of the regression model was low for time
      of first visit to the antenatal care unit and referrals for ultrasound
      examinations. CONCLUSIONS: With a reduced routine programme the surveillance
      became better apportioned to obstetric risk. Even a combination of medical or
      obstetric risk factors with socioeconomic characteristics explain only part of
      the variation in utilization of antenatal care.

PMID- 9923956
TI  - Hospital use by an ageing cohort: an investigation into the association between
      biological, behavioural and social risk markers and subsequent hospital
      utilization.
AB  - BACKGROUND: The aims of the study were to describe the pattern of hospital
      utilization (acute and mental health sectors) of the Paisley-Renfrew MIDSPAN
      cohort and assess the influence of biological, behavioural and social 'risk
      factors' (established at the time of screening) on subsequent hospital
      admissions. METHOD: A cohort analysis was carried out in Paisley and Renfrew, two
      post-industrial towns in West Central Scotland. This used a linked data set
      covering a 23 year follow-up period to combine original 'risk'-related data with
      subsequent routine hospital admissions data. The subjects were 8349 women and
      7057 men, aged 45-64 in the early to mid-1970s, and representing approximately 80
      per cent of the eligible population. The main outcome measures were patterns of
      hospital utilization (acute and mental health sectors), 'any acute hospital
      admission', 'a serious acute hospital admission' and 'death' (relative risks of
      each outcome were calculated for all risk factors). RESULTS: The following
      patterns of hospital utilization were found. Only 5 per cent experienced a mental
      health admission but mean stay was long (265 bed days per cohort member
      admitted). In contrast, 79 per cent experienced at least one acute hospital stay.
      The age-specific proportions of cohort members requiring admission increased over
      time but the growth in acute episodes was even higher (suggesting increasing
      rates of multiple admission). For non-survivors, 42 per cent of all acute
      episodes (55 per cent of bed days) took place during the 12 months before death.
      Analysis of risk factors (using Cox's proportional hazards model) of 'any
      admission' and 'a serious admission' showed forced expiratory volume (FEV1), age,
      sex, smoking status, blood pressure, blood sugar, body mass index, cholesterol
      and deprivation category to be important predictors. CONCLUSIONS: Despite the
      desirability of alternative settings of care for the chronically ill and dying, a
      high proportion of hospital bed days were required near the time of death. The
      absolute size of the demand for hospital services within the cohort was
      strikingly large and increasing over time. Strategies to address the tide of
      rising admissions will have to confront the increasing proportion of individuals
      requiring admission as well as the growth in multiple admissions. Those who were
      at higher risk of admission were the older members of the cohort (especially
      men), those with low FEV1, smokers, those who were underweight or obese, the
      small number with abnormal levels of blood sugar, those with high blood pressure
      and those who lived in the most deprived areas. Thus, programmes which affect
      these determinants of ill health may be useful in reducing age-specific admission
      rates.

PMID- 9923955
TI  - Trends in intentional injury deaths in children and teenagers (1980-1995).
AB  - BACKGROUND: The aim of the study was to describe patterns and trends in
      intentional injury death rates in children and teenagers. METHODS: Analyses were
      carried out on data from the Office of National Statistics on all intentional
      injury deaths in people aged 0 to 19 years, in England and Wales, from 1980 to
      1995. Trends in death rates were examined using Poisson regression modelling, and
      class-specific death rates were estimated using the Registrar General's Standard
      Classification of Occupations. RESULTS: Between 1980 and 1995, there has been a
      substantial fall in the unintentional injury death rate, but no reduction in the
      intentional injury death rate. Intentional injuries made up 13 per cent of injury
      and poisoning deaths in 1980, and 25 per cent of such deaths in 1995. Each year
      in England and Wales an average of 335 children and teenagers die as a result of
      homicide, suicide and injuries of undetermined intent. Older teenagers (15-19
      years) account for 70 per cent of intentional injury deaths, children 0-4 years
      account for 18 per cent, and children 5-15 years account for 12 per cent. Of the
      5361 intentional injury deaths, 45 per cent were classified as injury
      undetermined whether accidentally or purposely inflicted, 35 per cent were
      classified as suicide, and 20 per cent were classified as homicide. With the
      exception of suicide, there are steep social class gradients for each category of
      intentional injury. The homicide rate for children in social class V is 17 times
      that for children in social class I. For all intentional injury, homicide,
      suicide and injuries of undetermined intent, the relative risk of death for
      manual vs. non-manual was higher for the four year period 1992-1995 than in the
      four year period 1980-1983. CONCLUSIONS: Intentional injury is responsible for an
      average of 335 deaths of children and teenagers each year in England and Wales.
      Unlike for unintentional injury, there has been no reduction in death rates from
      intentional injury, which now accounts for 25 per cent of all injury deaths.
      There is a steep social class gradient in intentional injury death rates, which
      has widened over the period 1980-1995.

PMID- 9923957
TI  - Quarterly communicable disease review April to June 1998. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 9923958
TI  - The UK Annual Patient Satisfaction Survey: can it really reflect the quality of
      the NHS?

PMID- 9923959
TI  - Performance assessment.

PMID- 9923960
TI  - To reintroduce school BCG or abolish it - the dilemma for the newly formed health
      authorities.

PMID- 9923961
TI  - Does breast cancer screening depend on a wobbly hypothesis?

PMID- 9923962
TI  - Minor surgery and general practice.

PMID- 9923963
TI  - Increased uridine kinase (ATP: uridine 5'-phosphotransferase; EC 2.7.1.48)
      activity in human and rat tumors.
AB  - The activity of uridine kinase (ATP: uridine 5'-phosphotransferase; EC 2.7.1.48),
      the rate-limiting enzyme of the UMP salvage pathway, was measured in human
      ovaries and ovarian carcinomas, in a spectrum of six rat hepatomas of different
      growth rates and in eleven normal rat tissues of high and low cell renewal rates.
      In a standard isotopic method developed for the 100,000 x g fraction, uridine
      kinase activity was linear for 20 min and proportional with protein concentration
      over a range of 0.1 to 0.8 mg per 0.1 ml reaction mixture. The apparent Kms for
      uridine, ATP and Mg++ in normal rat liver were 5.0, 3.4 and 1.5 mM and in the
      rapidly growing hepatoma 3924A, 0.8, 2.1 and 1.1 mM, respectively. In normal
      control ACl/N and Buffalo strain rat livers, kinase activity ranged from 159 to
      180 nmol/h/mg protein. In hepatomas of slow and intermediate growth rates, kinase
      activity increased to 1.5- to 2.6-fold, and in hepatomas of rapid growth rates,
      to 5.1- to 5.8-fold over that of the relevant control, normal livers. When
      hepatoma 3924A tissue culture cells were plated and expressed their proliferative
      program, kinase activity increased to 2.1-fold in early log phase. To further
      clarify the linkage between uridine kinase and cell replicating capacity, the
      enzyme activity was measured in rat organs of high and low cell renewal. The
      kinase activity in liver of adult male Wistar rats was 176 +/- 6 nmol/h/mg
      protein. Activities in thymus, spleen and bone marrow were 4.7-, 2.1-, and 1.8
      fold, respectively, of rat liver values; in adipose tissue, the activities were
      low. The decay rates of uridine kinase were examined in rats injected with a high
      dose of cycloheximide, which inhibits protein biosynthesis by 90%. The t(1/2) of
      the kinase in rat bone marrow was 0.64 h, in rat liver longer than 6 h. In human
      ovary and ovarian carcinoma, the apparent Kms for uridine were 11.5 and 0.5 mM,
      respectively. In human ovary (n = 3), kinase activity was 38 nmol/hr/mg protein;
      in ovarian carcinoma (n = 6), the activity increased to 5- to 13-fold over that
      in ovary. The positive linkage of uridine kinase activity with proliferation and
      transformation is apparent in human ovarian carcinomas and in rat hepatomas of
      different growth rates. Therefore, the increased uridine kinase activity should
      be an interesting target for anticancer chemotherapy.

PMID- 9923964
TI  - Effect of vitamin C on androgen independent prostate cancer cells (PC3 and Mat-Ly
      Lu) in vitro: involvement of reactive oxygen species-effect on cell number,
      viability and DNA synthesis.
AB  - Studies have described the protective role of vitamin C (ascorbic acid) in
      certain types of cancer. In this study, we report the effects of vitamin C
      treatment of two androgen independent prostate cancer cell lines from human (PC3)
      and rat (Mat-Ly-Lu or MLL) sources. In vitro treatment of PC3 and MLL with sodium
      ascorbate acid (0-10 mM) resulted in a decrease in cell viability and thymidine
      incorporation into DNA. These effects of vit. C were dose and time dependent.
      Ascorbate induced these changes through the production of hydrogen peroxide since
      addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen
      peroxide, inhibited the effects of ascorbate on these cell lines. In contrast,
      superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen
      peroxide did not prevent ascorbate-induced changes emphasizing the involvement of
      reactive oxygen species (ROS) in cellular damage. That singlet oxygen scavengers
      such as sodium azide and hydroquinone, hydroxyl radical scavengers such as D
      mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbate on
      thymidine incorporation suggests that these free radicals are not involved in
      cellular damage. In conclusion, these results suggest that vitamin C inhibits
      tumor growth by virtue of producing reactive oxygen species. These results
      suggest that ascorbate is a potent anticancer agent for prostate cancer cells.

PMID- 9923965
TI  - Inhibition effect of propargylglycine on human fibrosarcoma HT-1080 cell
      invasiveness.
AB  - Effect of propargylglycine (2-Amino-4-pentynoic acid, PPG) on invasive property
      of human fibrosarcoma HT-1080 cell was investigated. PPG treatment of HT-1080
      significantly reduced the total cellular metallothioneins (MTs) contents, and the
      resistance of HT-1080 against heavy metals toxicity decreased with the decrease
      of the MTs contents. The HT-1080 cell invasion to reconstituted basement membrane
      Matrigel (MG) was inhibited by the PPG treatment in a PPG concentration-dependent
      fashion. The inhibition was due to the lowering of HT-1080 cells attachment to MG
      and degradation activity of matrix metalloproteinases (MMPs) secreted from HT
      1080 by the PPG treatment. However, the chemotactic ability of the PPG treated HT
      1080 was enhanced. Our results suggest that MTs concentration levels in a
      malignant tumor cell are closely related to its invasiveness, and if MTs level of
      tumor cell can be controlled, cancer metastasis may be able to be controlled.

PMID- 9923966
TI  - Enolase activity in chicken embryo primary retina cells is not affected by
      exposure to a 60-Hz electric field.
AB  - This study was to determine the extent of alteration of enolase specific
      activities in chicken embryo retina primary cells in culture when exposed to an
      ELF (extremely low frequency) electric field at 60 Hz. Results showed no
      alteration of enolase activity and enolase mRNA levels. In this study, sham vs.
      control experiments were also conducted to neutralize ambient AC magnetic fields,
      stray magnetic fields and variations in field uniformity. Under similar
      conditions, the specific activity of enolase is decreased in neuroblastoma cell
      line (NG108). It is apparent from this study that primary cells either are not
      affected by these exposure conditions or the effect is transient and warrants no
      damage.

PMID- 9923967
TI  - Extracellular glutamine level reduction enhances 5-fluorouracil cytotoxicity.
AB  - Cultured P388 (murine) and CEM (human) leukemia cells were exposed to medium
      including either 5-fluorouracil (5-FU) or methotorexate (MTX). The level of drug
      was less than the ID50 value obtained in RPMI 1640 medium (control). Enhancement
      of drug cytotoxicity was determined with medium in which asparagine or glutamine
      level had been reduced to 60% of the level of the control. Proliferation of both
      types of cells for 3 days showed the cytotoxicities of the drugs. Asparagine
      reduced medium showed no enhancement of cytotoxicity in comparison with control,
      while glutamine reduced medium enhanced the cytotoxicity of 5-FU, but not that of
      MTX. Regulation of extracellular glutamine level seemed to affect stage G1 of the
      cell cycle, as found in the previous result with adriamycin.

PMID- 9923968
TI  - The distribution of tissue fibronectin and sialic acid in human breast cancer.
AB  - Our findings indicate that sialic acid and fibronectin levels in breast tumors
      are higher than those in normal tissues. The mean tissue fibronectin and sialic
      acid concentrations for patients with breast cancer were 30.90 +/- 9.68 microg/mg
      protein and 21.60 +/- 9.35 microg/mg protein, respectively, and for normal
      controls were 12.47 +/- 5.69 microg/mg protein, respectively. Tissue fibronectin
      and sialic acid can be important markers for human breast cancer.

PMID- 9923969
TI  - The salubrious effects of ascorbic acid on cyclophosphamide instigated lipid
      abnormalities in fibrosarcoma bearing rats.
AB  - The combined effect of cyclophosphamide and ascorbic acid on plasma lipids and
      lipoprotein profiles are important since, ascorbic acid encumbered the lipid
      abnormalities initiated by cyclophosphamide during cancer chemotherapy. Hence,
      the study was launched to appraise the salutary role of ascorbic acid in
      cyclophosphamide administered fibrosarcoma bearing rats. Fibrosarcoma cell line
      induced rats were treated with cyclophosphamide (10 mg/kg body weight) and
      ascorbic acid (200 mg/kg body weight) individually and in combination for 28
      days. The concentration of plasma lipids and lipoprotein profiles were determined
      in control and experimental animals. The untreated, as well as cyclophosphamide
      administered fibrosarcoma bearing rats, divulged significantly increased levels
      of plasma total cholesterol, triglycerides, phospholipids, VLDL- and LDL
      cholesterol, as compared with their respective control animals. In contrast,
      ester and HDL-cholesterol levels exhibited a marked decrease in these animals.
      Similar observations were also noticed in liver lipid values, as well. However,
      these lipid abnormalities were corrected by the co-administration of ascorbic
      acid. These results suggested, that some clinical entanglement of
      cyclophosphamide was refrained by co-administration of ascorbic acid in tumor
      stress condition.

PMID- 9923971
TI  - A short synthetic peptide (DTRPAP) induces anti-mucin (MUC-1) antibody, which is
      reactive with human ovarian and breast cancer cells.
AB  - The present study describes the production of a synthetic hexapeptide (DTRPAP)
      based anti-mucin (MUC-1) antibody, similar to those produced using either the
      intact mucin antigen or tumor extracts. This antibody was generated by
      immunization of rabbits with the synthetic peptide conjugated to bovine serum
      albumin as a carrier. Using both the ELISA and FACS analysis methods, we have
      shown that the antibody is reactive with human ovarian and breast cancer cells,
      but not with normal epithelial breast cells. This antibody is different from the
      previously reported anti-mucin HMFG-1, HMFG-2 and SM-3 monoclonal antibodies,
      since competitive experiments with the free synthetic peptide revealed only a 30%
      inhibition of HMFG-1 binding to the ovarian (OVCAR-3) cancer cells, as compared
      to 78% inhibition of the anti-synthetic peptide antibody. The peptide was non
      inhibitory for HMFG-2, and induced a significant and reproducible stimulation of
      the SM-3 binding activity to the tumor cells.

PMID- 9923972
TI  - Plasma and erythrocyte total antioxidant status in patients with benign and
      malign breast disease.
AB  - The study was carried out on 25 women with breast cancer, 25 with fibrocystic
      breast disease and 19 healthy subjects. Antioxidant enzyme activities and total
      antioxidant status (AOX) were measured in erythrocyte and plasma of patients and
      healthies. Among the studied parameters, the erythrocyte Glutathione Peroxidase
      (GSH-Px) and Catalase (CAT) activities of patients with breast cancer were
      significantly different as compared to the control group values (p < 0.002 and p
      < 0.001) respectively. There was no correlation between total antioxidant status
      and any of these enzymes in erythrocyte and plasma activities of subjects.
      However, the positive correlation was found between erythrocyte and plasma
      Superoxide Dismutase [SOD(CuZn)] activities in all groups. Our results indicate
      that enzymatic and nonenzymatic antioxidants are differentially altered in human
      breast tumors. Since the total antioxidant status measurement isn't sufficient to
      evaluate the oxidant damage in breast disease, antioxidant enzymes must be
      measured separately in order to get additional information.

PMID- 9923970
TI  - Effects of detergents on P-glycoprotein atpase activity: differences in
      perturbations of basal and verapamil-dependent activities.
AB  - P-glycoprotein (P-gp), a plasma membrane glycoprotein associated with the
      multidrug resistance phenotype, is responsible for the ATP-dependent efflux of
      various amphiphilic drugs. Using membrane vesicles prepared from the multidrug
      resistant cell line DC-3F/ADX, we studied the perturbation of the basal (i.e. in
      the absence of drug) and verapamil-dependent P-gp ATPase activities induced by
      various detergents, at non-solubilizing, as well as at solubilizing,
      concentrations. The progressive membrane solubilization with increasing detergent
      concentration was monitored by light scattering and centrifugation experiments.
      For non-solubilizing detergent concentrations, all tested detergents except DOC
      induced a partial inhibition of P-gp ATPase activity, which was not correlated
      with the amount of the various tested detergents incorporated in the membranes.
      Analysis of the verapamil-induced P-gp activation reveals that P-gp ATPase
      activity is differently modulated by the various detergents at non-solubilizing
      concentrations. Thus, specific interactions between P-gp and detergents are more
      likely to occur rather than a global membrane perturbation. After solubilization
      by the various tested detergents, the basal P-gp ATPase activity was virtually
      completely inhibited, except in the presence of CHAPS which was able to preserve
      this activity at a level comparable to that measured in native membranes.
      However, the verapamil-induced P-gp ATPase activation was lost during P-gp
      solubilization by CHAPS, but recovered after dilution of CHAPS below its critical
      micellar concentration. These observations indicate specific interactions between
      P-gp and CHAPS molecules within the mixed micelles. On the whole, our data
      evidencing specific interactions P-gp/detergents are consistent with the location
      of the drug transport sites on P-gp transmembrane domains.

PMID- 9923973
TI  - Biochemical characterization of in vivo alkylating agent resistance of a murine
      EMT-6 mammary carcinoma. Implication for systemic involvement in the resistance
      phenotype.
AB  - While cancer drug resistance has been extensively studied in cell culture, little
      is known about more clinically relevant in vivo resistance. The in vivo
      resistance of a murine mammary carcinoma EMT-6 to alkylating agents was
      demonstrated in the present study to be associated with multiple biochemical
      changes. These included an up to 1.5-fold increase in activity of phase II drug
      metabolizing enzymes (DMEs), such as glutathione (GSH), glutathione reductase
      (GR), glutathione S-transferase (GST), glutathione peroxidase (GPX) and aldehyde
      dehydrogenase (ALDH), and an up to 88% decrease of phase I DME activity [7
      ethoxycumarin O-deethylase (ECOD), P450 reductase (PR)] in the resistant tumors
      compared with the parental tumor. Transplant of either parental or resistant
      tumors to mice was accompanied by a decrease of both phase I and phase II DME
      activity in the livers of female Balb/C mice compared with the non-tumor mice.
      Moreover, at the protein level, while cytochrome P450 (CYP) IIB1/2 in the liver
      of mouse bearing both the sensitive and the resistant tumor was significantly
      diminished compared to that in the liver of non-tumor control mouse in Western
      analysis, there was actually an increase of this protein in the liver of the host
      bearing either of the two resistant tumors compared to that of the sensitive
      tumor-bearing animal. Although this in vivo resistance phenotype is not expressed
      in cell culture, the profile of most of the enzyme changes in the resistant
      tumors remained similar in in vitro culture of the isolated tumor cells.
      Collectively, these results demonstrate that this in vivo alkylating agent
      resistance is associated with multiple changes of both phase I and phase II DMEs
      in the resistant tumors, and some of these, such as CYP IIB1/2 protein are
      further altered in the resistant tumor-bearing mouse liver, suggesting a
      potential role of systemic factors in this resistance phenotype.

PMID- 9923974
TI  - Activities of the enzymes participating in purine and free-radical metabolism in
      cancerous human colorectal tissues.
AB  - Activities of adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide
      dismutase, glutathione peroxidase and catalase enzymes were measured in cancerous
      and non-cancerous adjacent colorectal tissues from 10 patients. Activities of DNA
      turn-over enzymes (ADA, 5'NT and XO) were found increased and those of free
      radical metabolizing enzymes (SOD, GSH-Px and CAT) decreased in cancerous tissues
      compared with those of non-cancerous adjacent ones. Malondialdehyde (MDA)
      concentrations in cancerous tissues were also found higher than those of non
      cancerous tissues, which indicated accelerated lipid peroxidation in the
      cancerous tissues. In the correlation analysis, disordered enzymatical relations
      were observed between the enzymes of both metabolic pathways. Results suggest
      that activities of purine metabolizing enzymes increase to cope with accelerated
      purine metabolism in cancerous tissues and, enzymatic antioxidant defense
      potential of cancerous tissues decreases due to carcinogenic processes in the
      tissues. Reduced antioxidant defense system makes the cancerous tissue more
      vulnerable to toxic effects of some free-radical species.

PMID- 9923975
TI  - Evolution towards hormone independence of the MXT mouse mammary tumor is
      associated with a gradual change in its estrogen receptor molecular polymorphism.
AB  - Using a method based on [3H]tamoxifenaziridine ([3H]TAZ) labeling, sequential
      immunoadsorption with anti-ER monoclonal antibodies, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis(SDS-PAGE) and fluorography, we observed a
      striking change inthe estrogen receptor (ER) electrophoresis pattern of the
      transplantable MXT mouse mammary tumor. Early, ER "rich" tumors (approximately
      100 fmol/mg prot) displayed classical cytosolic 67 and 50 KDa bands. These bands
      disappeared in favor of a "cytosolic" 35 KDa band during progression towards
      undifferentiated ER "poor" tumors (approximately 25 fmol/mg prot). Although we
      can not rule out that this 35 KDa peptide results from in vivo ER proteolysis, it
      seems unique in view of the following: 1. It is immunoadsorbed not only by an
      anti-ER monoclonal antibody (H-222) directed to the hormone-binding domain, but
      also by an anti-ER monoclonal antibody (H-226) which interacts with an epitope in
      the A/B region close to the DNA-binding domain and is mainly exposed under
      activation conditions. 2. It does not bind [3H]estradiol([3H]E2) and a tentative
      to restore its [3H]E2 binding capacity with calmodulin and ATP was unsuccessful.
      The observation of similar approximately 35 KDa ERs in the nuclear fraction of
      early tumor transplants and in control uterus suggests that this peptide is
      already in an activated form. Structural alterations of ER and/or associated
      "anchorage" nuclear proteins may beat the origin of its cytosolic localization.
      Moreover, the fact that the addition of calmodulin and ATP to late MXT
      transplants cytosols fails to increase their [3H]E2 binding capacity indicates
      that the low ER content of these tumors does not result from a deficiency in the
      phosphorylation status of the receptor.

PMID- 9923976
TI  - Potentiation of the 5-aminolevulinic acid-based photodynamic therapy with
      cyclophosphamide.
AB  - We have investigated the efficacy of the Photodynamic Therapy (PDT) from 5
      aminolevulinic acid (ALA) in combination with an antineoplastic agent using an in
      vitro-in vivo model developed in our laboratory. The alkylant cyclophosphamide
      (CY) was chosen because there is evidence of the porphyrinogenic properties of
      this drug. Male BALB/c mice bearing a transplantable mammary adenoarcinoma were
      given two doses of 35 mg de CY/kg wt. i.p. and 9 mg/kg wt intratumorally. At 16,
      22 and 40 hrs after the last injection of CY the animals were sacrificed and
      explants of 2 mg of tumor were incubated 2 hrs in a medium containing 0.6 mM ALA;
      and then irradiated with a He-Ne laser. Innocula of 1 mm3 of irradiated and non
      irradiated tissue were then injected subcutaneously under the right and left
      flanks of a normal mouse, respectively. The efficacy of the treatment was
      determined following the growth of the tumor from day 10 after tumor
      implantation. Under the present conditions a 30% increased efficacy was observed
      in the case of the explants treated with CY 40 hrs after the last i.p. injection.
      Porphyrins in the liver and tumor and other tissues of the injected mice were
      also determined; except for a slight increase in tumor and liver, 40 and 22 hrs
      after CY i.p. injection respectively, no other changes were observed in any
      tissue, as compared with not CY treated mice. These results indicate that future
      treatment, combining the tumor localizing properties of endogenously formed
      porphyrins from ALA and antineoplasic drugs such as cyclophosphamide, should be
      encouraged.

PMID- 9923977
TI  - Nineteenth Annual Interdisciplinary Cancer Research Workshop.

PMID- 9923978
TI  - Metabotropic glutamate receptors are associated with non-synaptic appendages of
      unipolar brush cells in rat cerebellar cortex and cochlear nuclear complex.
AB  - Unipolar brush cells (UBCs) are a class of small neurons that are densely
      concentrated in the granular layers of the vestibulocerebellar cortex and dorsal
      cochlear nucleus. The UBCs form giant synapses with individual mossy fibre
      rosettes on the dendrioles which make up their brush formations and are provided
      with numerous, unusual non-synaptic appendages. In accord with the glutamatergic
      nature of mossy fibres, our previous post-embedding immunocytochemical studies
      indicated that various ionotropic glutamate receptor subunits are localized at
      the post-synaptic densities of the giant synapses, whereas the non-synaptic
      appendages are immunonegative. On the contrary, the metabotropic glutamate
      receptors mGluR1alpha and mGluR2/3 are situated at the non-synaptic appendages
      and are lacking at the post-synaptic densities. Other authors, however, have
      shown that antibodies to these metabotropic receptors stain both appendages and
      post-synaptic densities. In the present study, we have re-evaluated the
      distribution of metabotropic glutamate receptors in the UBCs of the cerebellum
      and the cochlear nuclear complex by light and electron microscopic pre-embedding
      immunocytochemistry with subtype-specific antibodies. We confirm that UBCs
      dendritic brushes are densely immunostained by antibody to mGluR1alpha
      particularly in the cerebellum and that antibody to mGluR2/3 labels at least a
      percentage of the UBC brushes in both the cerebellum and cochlear nuclei. At the
      ultrastructural level, it appears that mGluR1alpha and mGluR2/3
      immunoreactivities are not associated with the post-synaptic densities of the
      giant mossy fibre-UBC synapses, but instead are concentrated on the non-synaptic
      appendages of the cerebellar UBCs. The non-synaptic appendages, therefore, may be
      an important avenue for regulating the excitability of UBCs and mediating
      glutamate effects on their still unknown intracellular signal transduction
      cascades. We also show that the pre-synaptic densities of UBC dendrodendritic
      junctions are mGluR2/3 positive. As previously demonstrated, antibodies to
      mGluR1alpha and mGluR2/3 label subsets of Golgi cells. Antibody to mGluR5 does
      not stain UBCs in the cerebellum and cochlear nucleus and reveals the
      somatodendritic compartment of Golgi cells situated in the core of the cerebellar
      granular layer, whilst cochlear nucleus Golgi cells are mGluR5 negative.

PMID- 9923979
TI  - Distribution of mitochondria within Muller cells--I. Correlation with retinal
      vascularization in different mammalian species.
AB  - The distribution of mitochondria within retinal glial (Muller) cells and neurons
      was studied by electron microscopy, by confocal microscopy of a mitochondrial dye
      and by immunocytochemical demonstration of the mitochondrial enzyme GABA
      transaminase (GABA-T). We studied sections and enzymatically dissociated cells
      from adult vascularized (human, pig and rat) and avascular or pseudangiotic
      (guinea-pig and rabbit) mammalian retinae. The following main observations were
      made. (1) Muller cells in adult euangiotic (totally vascularized) retinae contain
      mitochondria throughout their length. (2) Muller cells from the periphery of
      avascular retinae display mitochondria only within the sclerad-most end of Muller
      cell processes. (3) Muller cells from the vascularized retinal rim around the
      optic nerve head in guinea-pigs contain mitochondria throughout their length. (4)
      Muller cells from the peripapillar myelinated region ('medullary rays') of the
      pseudangiotic rabbit retina contain mitochondria up to their soma. In living
      dissociated Muller cells from guinea-pig retina, there was no indication of low
      intracellular pH where the mitochondria were clustered. These data support the
      hypothesis that Muller cells display mitochondria only at locations of their
      cytoplasm where the local O2 pressure (pO2) exceeds a certain threshold. In
      contrast, retinal ganglion cells of guinea-pig and rabbit retinae display many
      mitochondria although the local pO2 in the inner (vitread) retinal layers has
      been reported to be extremely low. It is probable that the alignment of
      mitochondria and the expression of mitochondrial enzymes are regulated by
      different mechanisms in various types of retinal neurons and glial cells.

PMID- 9923980
TI  - Distribution of mitochondria within Muller cells--II. Post-natal development of
      the rabbit retinal periphery in vivo and in vitro: dependence on oxygen supply.
AB  - The occurrence and localization of mitochondria within glial (Muller) cells and
      neurons of the peripheral (avascular) rabbit retina was studied electron
      microscopically and by immunocytochemical demonstration of the mitochondrial
      enzyme GABA transaminase (GABA-T). Post-natal development in vivo was compared
      with development of organ cultures from neonatal rabbit retinae, grown over 2
      weeks in vitro. The adult pattern of mitochondrial localization (restriction to
      the sclerad end of the cells) was observed from the beginning of enzyme
      expression at early post-natal stages. However, when neonatal retinal pieces were
      grown in vitro with their vitread surface exposed to the air, their Muller cells
      contained mitochondria along most of their length. When functionally developed
      retinae from postnatal day 14 were explanted in vitro, they retained their
      sclerad mitochondrial distribution for almost 24 h but thereafter the inner
      portions of their cytoplasm became occupied by mitochondria within a few hours.
      This was achieved mainly by mitochondrial migration rather than by formation of
      new mitochondria because it was not prevented by cycloheximide-induced inhibition
      of protein synthesis. These data support the following hypotheses: (1) the
      mitochondrial distribution in Muller cells is determined by the local cytoplasmic
      O2 pressure (pO2), (2) existing mitochondria move towards cytoplasmic regions of
      sufficient pO2 by rather rapid migration and (3) the start of this migration is
      delayed by almost 24 h due to the action of as yet unknown control mechanisms. In
      contrast, the mitochondrial content of retinal ganglion and amacrine cells in the
      vitread retinal layers was virtually independent of the source and level of
      oxygen supply.

PMID- 9923981
TI  - Quantitative freeze-fracture analysis of the frog neuromuscular junction synapse-
      I. Naturally occurring variability in active zone structure.
AB  - The orderly arrays of intramembranous particles (IMPs) found in the p-face of
      freeze-fracture replicas of the frog neuromuscular junction ('active zones') are
      believed to be involved in transmitter release. Some or all of the particles
      represent voltage-dependent Ca2+ channels. Since there is a great heterogeneity
      in the amount of transmitter released by different frog motor nerve terminals we
      sought to determine whether active zone (AZ) structure displayed a similar
      heterogeneity by using a novel freeze-fracture procedure providing large, intact
      replicas containing significant portions of motor nerve terminals from the
      cutaneous pectoris muscle of the frog, Rana pipiens. Using only junctions in
      which more than 50 AZs or more than 50 microm of nerve terminal were included in
      the fractures, we measured AZ length, AZ intramembranous particle density,
      terminal width at each AZ, space between AZs, the angle of AZ orientation with
      respect to the longitudinal axis of the nerve terminal, exposed pre-synaptic
      nerve terminal surface area and a calculated value for mean AZ length per unit
      terminal length. The analysis led to the following conclusions. There is an
      approximate 5-fold range in mean AZ length/micrometre terminal length. Terminal
      width is a good predictor of AZ length. Particle density does not vary
      significantly within a given AZ, nor between AZs from the same or different
      junctions. The distance between AZs is not related to AZ length, i.e. shorter AZs
      are no more or less likely to be closer to the adjacent AZ. The probability of
      release from any AZ on action potential invasion is small. If most of the IMPs
      are Ca2+ channels, either the probability of channel opening or the efficacy of
      triggering release is very low or both. That the variability in release efficacy
      in different terminals is much greater than ultrastructural variability in
      terminals suggests that regulation of release is dominated by physiological
      processes that do not have obvious ultrastructural correlates. On the other hand,
      the apparent excess of AZ relative to the number of vesicles released indicates
      that the amount and variability in amount of AZ is important in ways that need to
      be elucidated.

PMID- 9923982
TI  - Quantitative freeze-fracture analysis of the frog neuromuscular junction synapse-
      II. Proximal-distal measurements.
AB  - Neurotransmitter release from different parts of frog motor nerve terminals is
      often non-uniform. There is a decrease in release efficacy from the distal
      regions of frog motor nerve terminal branches. Since release is thought to occur
      near the double arrays of large intramembranous particles that constitute the pre
      synaptic active zones (AZs), we have examined quantitatively the proximal-distal
      distribution of AZ structure, using a novel freeze-fracture technique that
      produces replicas of large fractions of terminals, including the region of nerve
      entry. This enables us to know the proximal distal orientation of each branch.
      From 23 end-plates we have obtained fractures of 72 branches. For 27 of these
      branches we have obtained continuous fractures both greater than 25 microm in
      length and with sufficient information to determine their proximal distal
      polarity. Only a few of these branches showed a marked distal decrease in AZ
      length/unit length of terminal, while several junctions had short regions (5-10
      microm), either proximally or distally, that exhibited amounts of AZ that were
      substantially greater or smaller than the mean value for that terminal branch.
      The terminal area, post-synaptic gutter width and nerve terminal width all
      exhibit some distal decline concomitant with the distal tapering of nerve
      terminal branches. AZ length tends to have the least decline compared to the
      other parameters. Thus, the vast majority of frog motor nerve terminal branches
      do not display a significant proximal-distal gradient in the amount of AZ
      structure / microm terminal length. The present data do not provide an obvious
      ultrastructural correlate for the distal decline in transmitter release that some
      authors have observed.

PMID- 9923983
TI  - Attitudes to hearing difficulty and hearing aids and the outcome of audiological
      rehabilitation.
AB  - First time hearing aid candidates (N = 135) in a NHS setting were administered
      the Hearing Attitudes in Rehabilitation Questionnaire (HARQ) designed to assess
      attitudes to acquired hearing loss and hearing aids and 92% of them were followed
      up 3-9 months after fitting. Attitude scores, age, sex and sensory thresholds
      were related to six self-report outcome measures by use of logistic regression.
      The major findings were that patients who were least distressed by their hearing
      difficulties and reported not wanting or needing a hearing aid used their aids
      least frequently and evaluated them less highly in listening situations. An
      attitude that wearing a hearing aid was stigmatizing was not predictive of
      outcome except a report of more difficulty in handling the aid. There were some
      low but significant correlations between attitudes and sensory thresholds and
      thresholds also contributed to the prediction of outcome in a few instances.

PMID- 9923984
TI  - Use of homeopathy in the treatment of tinnitus.
AB  - Tinnitus is a prevalent condition which has no practical and effective
      pharmacological treatment. In the absence of relief by conventional routes,
      sufferers are increasingly turning to 'alternative' or 'complementary' medicine.
      This paper reports the evaluation of a homeopathic preparation 'Tinnitus' by a
      double-blind, placebo-controlled clinical trial. The remedy was taken in tablet
      form at a homeopathic D60 potency. Perceived intensity and intrusiveness of the
      tinnitus was assessed at four points during the trial by subjective procedures
      (visual analogue scales and questionnaires) and by a battery of audiological
      measurements. Although questionnaire responses indicated that the homeopathic
      preparation was preferred to placebo by 14 of the 28 subjects, an analysis of
      variance indicated that neither the VAS scores nor the audiological measures
      showed significant improvement in tinnitus symptoms in response to 'Tinnitus'
      versus the placebo. It was concluded that 'Tinnitus' could not be shown to be
      more effective than the matched placebo.

PMID- 9923985
TI  - Automatic classification of transiently evoked otoacoustic emissions using an
      artificial neural network.
AB  - The increasing use of transiently evoked otoacoustic emissions (TEOAE) in large
      neonatal hearing screening programmes makes a standardized method of response
      classification desirable. Until now methods have been either subjective or based
      on arbitrary response characteristics. This study takes an expert system approach
      to standardize the subjective judgements of an experienced scorer. The method
      that is developed comprises three stages. First, it transforms TEOAEs from
      waveforms in the time domain into a simplified parameter set. Second, the
      parameter set is classified by an artificial neural network that has been taught
      on a large database TEOAE waveforms and corresponding expert scores. Third,
      additional fuzzy logic rules automatically detect probable artefacts in the
      waveforms and synchronized spontaneous emission components. In this way, the
      knowledge of the experienced scorer is encapsulated in the expert system software
      and thereafter can be accessed by non-experts. Teaching and evaluation of the
      neural network was based on TEOAEs from a database totalling 2190 neonatal
      hearing screening tests. The database was divided into learning and test groups
      with 820 and 1370 waveforms respectively. From each recorded waveform a set of 12
      parameters was calculated, representing signal static and dynamic properties. The
      artifical network was taught with parameter sets of only the learning groups.
      Reproduction of the human scorer classification by the neural net in the learning
      group showed a sensitivity for detecting screen fails of 99.3% (299 from 301
      failed results on subjective scoring) and a specificity for detecting screen
      passes of 81.1% (421 of 519 pass results). To quantify the post hoc performance
      of the net (generalization), the test group was then presented to the network
      input. Sensitivity was 99.4% (474 from 477) and specificity was 87.3% (780 from
      893). To check the efficiency of the classification method, a second learning
      group was selected out of the previous test group, and the previous learning
      group was used as the test group. Repeating learning and test procedures yielded
      99.3% sensitivity and 80.7% specificity for reproduction, and 99.4% sensitivity
      and 86.7% specificity for generalization. In all respects, performance was better
      than for a previously optimized method based simply on cross-correlation between
      replicate non-linear waveforms. It is concluded that classification methods based
      on neural networks show promise for application to large neonatal screening
      programmes utilizing TEOAEs.

PMID- 9923987
TI  - British Society of Audiology Short Papers Meeting on Experimental Studies of
      Hearing and Deafness: British Journal of Audiology, 32.2, 1998.

PMID- 9923986
TI  - Bilateral otoacoustic emissions pass in a baby with Mondini deformity and
      subsequently confirmed profound bilateral hearing loss.
AB  - Evoked otoacoustic emissions are well established as a hearing screening
      technique and are used extensively in paediatric audiology. They are believed to
      originate from the outer hair cells and can be detected in almost 100% of
      normally hearing ears; even a mild hearing loss has been shown to abolish
      otoacoustic emissions. Results are presented of a baby boy born at 29 weeks'
      gestation requiring 77 days of neonatal care, but experiencing no complications
      following discharge from the neonatal unit. This child had clear bilateral evoked
      otoacoustic emissions at almost four months of age, but was subsequently found to
      have a profound bilateral hearing impairment and absent otoacoustic emissions.
      Radiological investigations revealed bilateral Mondini dysplasia, and this child
      has now been implanted with a multi-channel MXM Digisonic cochlear implant. He is
      progressing well and shows awareness of sound. Approximately 10 previous cases of
      otoacoustic emissions occurring in profoundly deaf ears have been reported in the
      literature. Although it is likely that this child's hearing loss was progressive
      in nature, the authors believe that this is the first reported case of
      otoacoustic emissions being recorded in the presence of Mondini dysplasia. This
      raises concerns about the use of neonatal screening in isolation without adequate
      mechanisms for later identification of hearing impairment, although it is
      acknowledged that it represents a rare situation.

PMID- 9923988
TI  - Response to Stockwell CW. Vestibular testing: Past, present, future. Br J Audiol
      1997; 31: 387-398.

PMID- 9923989
TI  - Comparison of regional myocardial velocities assessed by quantitative 2
      dimensional and M-mode color Doppler tissue imaging: influence of the signal-to
      noise ratio of color Doppler myocardial images on velocity estimators of the
      Doppler tissue imaging system.
AB  - M-mode color Doppler imaging of the myocardium affords a greater sampling rate
      and signal-to-noise (S/N) ratio than 2-dimensional (2D) imaging. In this study,
      we compared myocardial velocities assessed by 2D and M-mode Doppler tissue
      imaging (DTI) at the same site and evaluated the influence of the S/N ratio on
      velocity estimates of the currently used DTI systems. In patients with and
      without impaired regional left ventricular function, myocardial velocities
      assessed by 2D DTI were lower than those obtained with M-mode DTI. The difference
      between regional velocities derived from both imaging techniques was positively
      correlated with the extent of the "black zone," which could be considered as
      indirectly reflecting the S/N ratio for each frame. Thus in the clinical setting
      and on currently used echocardiographs, 2D DTI may provide underestimated
      regional myocardial velocities when compared with M-mode, mainly because of the
      influence of the lower sampling rate and S/N ratio on velocity estimators of the
      imaging system.

PMID- 9923990
TI  - Left ventricular diastolic properties of hypertensive patients measured by pulsed
      tissue Doppler imaging.
AB  - Examination of left ventricular (LV) diastolic dysfunction in hypertensive
      patients has been based on parameters obtained from the transmitral flow velocity
      during pulsed Doppler echocardiography. However, these parameters are affected by
      loading conditions. We evaluated LV diastolic function along the longitudinal and
      transverse axes by pulsed tissue Doppler imaging (TDI) in 50 hypertensive (HT)
      patients and 36 age-matched healthy volunteers (N). Transmitral flow velocity was
      recorded by pulsed Doppler echocardiography. LV posterior wall motion velocity
      along the longitudinal and transverse axes also was recorded by pulsed TDI. In
      both groups, peak early diastolic velocity of the LV posterior wall (Ew) along
      the transverse axis (N: 15.8+/-5.2 cm/s, HT: 12.2+/-4.4 cm/s) was higher than
      that along the longitudinal axis (N: 12.7+/-3.1 cm/s, HT: 9.5+/-3.3 cm/s). Peak
      atrial systolic velocity of the LV posterior wall (Aw) along the longitudinal
      axis (N: 9.1+/-1.8 cm/s, HT: 9.7 +/-2.6 cm/s) significantly exceeded that along
      the transverse axis (N: 8.0+/-2.2 cm/s, HT: 8.4+/-2.4 cm/s) in both groups. The
      Ews were lower and the Aws were higher along both axes in the patient group than
      in the control group. The time intervals from the aortic component of the second
      heart sound to the peak of the early diastolic wave (IIA-Ews) along both the
      transverse (N: 142+/-18 ms, HT: 154+/-19 ms) and longitudinal (N: 151 16 ms, HT:
      162+/-20 ms) axes were longer in the patient group. In 29 patients, Ews along
      both axes correlated negatively (transverse: r = -0.80, P < .0001; longitudinal:
      r = -0.71, P < .0001) and IIA-Ews correlated positively (transverse: r = 0.81, P
      < .0001; longitudinal: r = 0.74, P < .001) with the time constant of the LV
      pressure decay during isovolumic diastole. The Aws along both axes in the 24
      patients without pseudonormalization in transmitral flow velocity correlated
      positively (transverse: r = 0.60, P < .001; longitudinal: r = 0.74, P < .0001)
      with the LV end-diastolic pressure. In conclusion, LV relaxation and filling
      along the longitudinal and transverse axes were impaired in many patients with
      hypertension. Pulsed TDI was useful for evaluating LV diastolic dynamics in this
      disease.

PMID- 9923991
TI  - Three-dimensional echocardiographic determination of left ventricular volumes and
      function by multiplane transesophageal transducer: dynamic in vitro validation
      and in vivo comparison with angiography and thermodilution.
AB  - The goal of this study was to validate 3-dimensional echocardiography by
      multiplane transesophageal transducer for the determination of left ventricular
      volumes and ejection fraction in an in vitro experiment and to compare the method
      in vivo with biplane angiography and the continuous thermodilution method. In the
      dynamic in vitro experiment, we scanned rubber balloons in a water tank by using
      a pulsatile flow model. Twenty-nine measurements of volumes and ejection
      fractions were performed at increasing heart rates. Three-dimensional
      echocardiography showed a very high accuracy for volume measurements and ejection
      fraction calculation (correlation coefficient, standard error of estimate, and
      mean difference for end-diastolic volume 0.998, 2.3 mL, and 0.1 mL; for end
      systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%,
      and -0.4%, respectively). However, with increasing heart rate there was
      progressive underestimation of ejection fraction calculation (percent error for
      heart rate below and above 100 bpm 0.59% and -8.6%, P < .001). In the in vivo
      study, left ventricular volumes and ejection fraction of 24 patients with
      symmetric and distorted left ventricular shape were compared with angiography
      results. There was good agreement for the subgroup of patients with normal left
      ventricular shape (mean difference +/-95% confidence interval for end-diastolic
      volume 5.2+/-6.7 mL, P < .05; for end-systolic volume -0.5+/-8.4 mL, P = not
      significant; for ejection fraction 2.4%+/-7.2%, P = not significant) and
      significantly more variability in the patients with left ventricular aneurysms
      (end-diastolic volume 23.1+/-56.4 mL, P < .01; end-systolic volume 5.6+/-41.0 mL,
      P = not significant; ejection fraction 4.9%+/-16.0%, P < .05). Additionally, in
      20 critically ill, ventilated patients, stroke volume and cardiac output
      measurements were compared with measurement from continuous thermodilution.
      Stroke volume as well as cardiac output correlated well to thermodilution (r =
      0.89 and 0.84, respectively, P < .001), although both parameters were
      significantly underestimated by 3-dimensional echocardiography (mean difference
      +/-95% confidence interval = -6.4+/-16.0 mL and -0.6+/-1.6 L/min, respectively, P
      < .005).

PMID- 9923992
TI  - Duration of pulmonary venous atrial reversal flow velocity and mitral inflow a
      wave: new measure of severity of cardiac amyloidosis.
AB  - Transmitral Doppler flow patterns of patients with cardiac amyloidosis evolve
      from an early impaired relaxation to an advanced restrictive pattern. This
      reflects increasing severity of diastolic dysfunction and hence left ventricular
      filling pressures. The duration of the pulmonary venous atrial reversal flow was
      recently shown to exceed that of the mitral inflow A wave in patients with left
      ventricular end-diastolic pressure greater than 15 mm Hg. The objective of this
      study was to assess the utility of this index as a measure of the severity of
      cardiac amyloidosis. Comprehensive transthoracic 2-dimensional and pulsed-wave
      Doppler echocardiograms of the pulmonary venous and transmitral flows were made
      of 23 patients (10 women) with biopsy-proven diagnosis of primary systemic
      amyloidosis and of 49 subjects as age-matched normal controls. The amyloidosis
      group was divided into non-restrictive and restrictive subgroups on the basis of
      the patients' transmitral inflow deceleration time (>150 and < or =150 ms,
      respectively). The durations of the pulmonary venous atrial reversal and mitral
      inflow A wave were measured, and the differences between the flow durations were
      compared with the control and published data in the nonrestrictive and
      restrictive groups. The mean duration of the pulmonary venous atrial reversal was
      significantly longer in the amyloid than the control group (P < .01). The mean
      duration of the mitral inflow A wave was significantly shorter in the restrictive
      group than both the nonrestrictive and the control groups (P < .05). The duration
      of the pulmonary venous atrial reversal exceeded that of the mitral inflow A wave
      in all patients with cardiac amyloidosis. The difference in duration between
      pulmonary venous atrial reversal and mitral inflow A wave was significantly
      greater in the amyloidosis group compared with the normal group, and this index
      varied significantly within the amyloid group between the abnormal relaxation and
      the restrictive groups. The difference in the duration between the pulmonary
      venous atrial reversal and the mitral inflow A wave is a reliable index of
      diastolic function and can be used to assess the severity of cardiac amyloidosis.

PMID- 9923993
TI  - Effect of gender and left ventricular dysfunction on the incidence of hypotension
      induced by dobutamine stress echocardiography.
AB  - BACKGROUND: Of patients who undergo dobutamine stress echocardiography (DSE), 14%
      to 38% experience hypotension that sometimes requires termination of the test
      before an adequate cardiac work-load is reached. The mechanisms of hypotension
      reportedly are related to peripheral vasodilation, a decrease in cardiac output,
      and left ventricular (LV) cavity obliteration. DSE is performed increasingly in
      women and in patients with LV dysfunction. However, the impact of gender and LV
      dysfunction on DSE-induced hypotension has not been elucidated. METHODS AND
      RESULTS: Clinical, hemodynamic, and echocardiographic characteristics were
      studied in 412 patients undergoing DSE, 82 patients with an LV ejection fraction
      of 40% or less, and 147 women. Hypotension, defined as a decrease in systolic
      blood pressure of at least 20 mm Hg, occurred in 117 (28%) patients. Hypotension
      was more common in women than men (36% vs 24%, P = .01). Hypotension was also
      more common in older adults (P = .004), persons taking diuretics (P = .025) or
      angiotensin-converting enzyme inhibitors (P = .01), and persons with higher
      baseline blood pressures (P < .0001). Hypotension was not related to the use of
      beta blockers, calcium channel blockers, digoxin, nitrates, LV dimensions, or
      ejection fraction. CONCLUSIONS: The incidence of DSE-induced hypotension is
      related to gender but not to the level of LV systolic function. It also is
      associated significantly with higher age, and use of angiotensin-converting
      enzyme inhibitors or diuretics.

PMID- 9923994
TI  - Importance of intraoperative transesophageal echocardiography during coronary
      artery surgery without cardiopulmonary bypass.
AB  - The goal of this study was to assess left ventricular segmental wall motion (SWM)
      abnormalities during coronary artery bypass grafting (CABG) without
      cardiopulmonary bypass (CPB), and its impact on the immediate postoperative
      outcome. Transesophageal echocardiography was used intraoperatively in 27
      patients (mean age 57 years) who had CABG without CPB. Images obtained with a 5
      MHz biplane transesophageal echocardiographic probe in the transgastric and
      transesophageal planes were recorded before, during, and after 48 coronary artery
      clampings for saphenous vein or internal mammary artery anastomosis.
      Transthoracic echocardiography was performed 1 day before surgery and on the
      seventh postoperative day. During the 48 coronary artery clampings, 31 (64%) new
      SWM abnormalities were found. At the time of chest closure, complete recovery
      occurred in 16 (50%) segments, partial recovery in 10 (33%), and no recovery in 5
      (17%). On the seventh postoperative day the new SWM abnormalities persisted in
      all 5 segments without recovery at the end of the surgery and in 2 of 10
      (20%)segments with partial recovery (group 1). Group 1 had higher variation on
      the echocardiographic point score index between the beginning and end of surgery,
      higher enzymatic levels, more ST-T changes on the electrocardiogram, and more
      clinical problems than group 2 (patients without new SWM abnormalities on the
      seventh postoperative day) (P < .05). We concluded that new SWM abnormalities of
      the left ventricle occur during CABG without CPB as assessed by intraoperative
      transesophageal echocardiography. Persistence of these abnormalities at the end
      of surgery may be a predictor of SWM dysfunction and clinical problems in the
      immediate postoperative period.

PMID- 9923995
TI  - Simultaneous Doppler and catheter transvalvular pressure gradients across St Jude
      bileaflet mitral valve prosthesis: in vivo study in a chronic animal model with
      pediatric valve sizes.
AB  - A mixture of valve types has been used in previous in vivo studies to assess the
      accuracy of Doppler echocardiography compared with catheter-measured pressure
      gradients across prosthetic mitral valves. However, limited data exist regarding
      the most commonly used bileaflet mechanical valve. We studied 14 sheep with St
      Jude Medical mechanical mitral valves. Continuous wave Doppler data were obtained
      across each of the 3 valve orifices. Hemodynamic data were obtained
      simultaneously by direct measurements with catheters. Valve sizes commonly used
      in the pediatric population in the mitral position (23 mm, 25 mm, and 27 mm) were
      studied. Linear regression analyses of Doppler-predicted versus catheter-measured
      gradients provided correlation coefficients ranging from 0.75 to 0.91. Agreement
      analysis demonstrated a scatter of Doppler data about the regression line.
      Although a reasonably good correlation of Doppler-predicted peak and mean
      pressure gradients across bileaflet mechanical valves exists in the mitral
      position, caution is needed when this method is applied to patients. Doppler
      overestimation was greatest across the 23-mm valves. Analyses of the specific
      orifice interrogated demonstrated higher estimated pressure gradients across the
      central orifice compared with the side orifices.

PMID- 9923996
TI  - Transesophageal echocardiographic diagnosis of a mycotic ascending aortic
      pseudoaneurysm as a source of embolism.
AB  - Pseudoaneurysm of the ascending aorta may develop after aortic injury from trauma
      or surgery. We report a case of dehiscence of an aortic graft leading to
      ascending aortic pseudoaneurysm that was diagnosed by transesophageal
      echocardiography. In addition, the transesophageal echocardiogram identified the
      pseudoaneurysm as the likely cause of a saddle embolus to the iliac bifurcation
      of the aorta. This case is also unique in that the patient's pseudoaneurysm was
      infected with fungus.

PMID- 9923997
TI  - Echocardiographically diagnosed cardiac echinococcus complicated by embolic
      intraventricular thrombus.
AB  - A young woman had cerebral embolism caused by an unusual complication of an
      asymptomatic cardiac hydatid cyst. The diagnosis of the cyst by means of
      echocardiography was confirmed by surgery as well as nuclear magnetic resonance,
      computed tomography, and serologic tests. Transesophageal echocardiography
      revealed a thrombus in the left ventricle that was situated aside the cyst. It
      was thought to be the source of an embolus. Surgical removal of the cyst was
      successful. Cerebral damage was reduced by administration of heparin.

PMID- 9923998
TI  - Ischemic neurologic event in a child as a result of ventricular septal aneurysm.
AB  - Aneurysm of the interventricular septum without a shunt was found by means of
      transthoracic echocardiography in a 6-year-old boy with acute hemiparesis. Until
      the time of the incident, he had been healthy. The aneurysmal sac contained 2
      clots, presumably resulting in the ischemic cerebral infarct. On the basis of the
      echocardiographic scan, successful surgery was performed. To the best of our
      knowledge, this is the first report describing such dramatic sequelae of
      interventricular septal aneurysm.

PMID- 9923999
TI  - Large gradient across a partially ligated left atrial appendage.
AB  - The left atrial appendage is frequently ligated during mitral valve surgery to
      decrease the future risk of embolic events. The postoperative detection of a
      partially occluded left atrial appendage has previously been reported with the
      use of transesophageal echocardiography. We describe an unusual case in which
      Doppler echocardiography demonstrated a remarkably high-velocity jet emanating
      from a partially ligated left atrial appendage.

PMID- 9924000
TI  - Pan-valvular annular calcification in Takayasu's arteritis: report of 3 cases.
AB  - Takayasu's arteritis is a chronic inflammatory arteriopathy. It mainly affects
      the aortic arch and its main branches. The aortic valve annulus and coronary and
      pulmonary arteries are rarely affected. Mitral and tricuspid annular
      calcification were not reported previously. We identified mitral annular
      calcification by using transthoracic echocardiography in 3 patients with
      Takayasu's arteritis, in whom none had any of the reported causes of mitral
      annular calcification. Two of them had concomitant tricuspid and aortic annular
      calcification.

PMID- 9924001
TI  - Left atrial leiomyosarcoma: double occurrence and double recurrence--report of
      one case.
AB  - In October 1996 a 67-year-old man underwent transthoracic and transesophageal
      echocardiography (TEE) because of dyspnea on exertion and was found to have 2
      left atrial cardiac masses. The 2 masses were surgically removed from the atrium
      and showed histopathologic and ultrastructural features of a leiomyosarcoma.
      Seven months later a double recurrence of left atrial masses was found with TEE;
      the patient refused surgery and decided instead to receive chemotherapy. In May
      1998 he was in stable condition (New York Heart Association class III), but a
      further growth of the 2 left atrial masses was observed at TEE. We describe the
      echocardiographic features of the 2 cardiac masses and the clinical and
      prognostic implications.

PMID- 9924003
TI  - El Nino and the dynamics of vectorborne disease transmission.
AB  - The objective of the study was to investigate the relationship between reported
      incidence of dengue fever and El Nino southern oscillation (ENSO) in 14 island
      nations of the South Pacific. Using a mixed ecological study design, we
      calculated correlations between annual averages of the southern oscillation index
      (SOI), local temperature and rainfall, and dengue fever. We also calculated
      temporal correlations between monthly reports of dengue fever cases on different
      islands. There were positive correlations between SOI and dengue in 10 countries.
      In five of these (including all of the larger islands) there were also positive
      correlations between SOI and estimates of local temperature and/or rainfall.
      There were temporal correlations between monthly reports of dengue cases within
      two groups of countries. Climate changes associated with ENSO may trigger an
      increase in dengue fever transmission in larger, more populated islands where the
      disease is endemic. There was also evidence of propagation of infection from
      larger islands to smaller neighbors. Unlike the initiation of epidemics, this
      transfer between islands appears to be independent of interannual climate
      variations, pointing to the importance of modulating factors in dengue
      transmission such as population density and travel. In the future, models of the
      impact of climate change must attempt to account for these factors.

PMID- 9924002
TI  - Developmental synergism of steroidal estrogens in sex determination.
AB  - Gonadal sex in the red-eared slider turtle, Trachemys scripta, is determined by
      incubation temperature during embryonic development. Evidence suggests that
      temperature determines sex by influencing steroid hormone metabolism and/or
      sensitivity: steroidogenic enzyme inhibitors or exogenous sex steroid hormones
      and their man-made analogs override (or enhance) temperature effects on sex
      determination. Specifically, nonaromatizable androgens and aromatase inhibitors
      induce testis differentiation at female-producing temperatures, whereas
      aromatizable androgens and estrogens induce ovary differentiation at male
      producing temperatures. Moreover, natural estrogens and temperature synergize to
      produce more females than would be expected if estrogens and temperature had
      purely additive effects on sex determination. In this study, we use sex reversal
      of turtle embryos incubated at a male-producing temperature to examine synergism
      among steroidal estrogens: estrone, 17ss-estradiol, and estriol. A low dose of
      17ss-estradiol (200 ng) showed significant synergism when administered with a
      single low dose of estriol (10 ng). Likewise, a single low dose of estrone (250
      ng) had a synergistic effect when combined with the same low dose of estriol (10
      ng). We conclude that the weak natural estrogens estrone and 17ss-estradiol
      synergize with a low dose of the more potent estriol to reverse gonadal sex
      during the critical period of sexual differentiation. These results suggest that
      weak environmental estrogens may also synergize with stronger natural estrogens.

PMID- 9924004
TI  - Exposure estimates to disinfection by-products of chlorinated drinking water.
AB  - Exposure to disinfection by-products (DBPs) of drinking water is multiroute and
      occurs in households serviced by municipal water treatment facilities that
      disinfect the water as a necessary step to halt the spread of waterborne
      infectious diseases. Biomarkers of the two most abundant groups of DBPs of
      chlorination, exhaled breath levels of trihalomethanes (THMs) and urinary levels
      of two haloacetic acids, were compared to exposure estimates calculated from in
      home tap water concentrations and responses to a questionnaire related to water
      usage. Background THM breath concentrations were uniformly low. Strong
      relationships were identified between the THM breath concentrations collected
      after a shower and both the THM water concentration and the THM exposure from a
      shower, after adjusting for the postshower delay time in collecting the breath
      sample. Urinary haloacetic acid excretion rates were not correlated to water
      concentrations. Urinary trichloroacetic acid excretion rates were correlated with
      ingestion exposure, and that correlation was stronger in a subset of individuals
      who consumed beverages primarily within their home where the concentration
      measurements were made. No correlation was observed between an average 48-hr
      exposure estimate and the urinary dichloroacetic acid excretion rate, presumably
      because of its short biological half-life. Valid biomarkers were identified for
      DBP exposures, but the time between the exposure and sample collection should be
      considered to account for different metabolic rates among the DBPs. Further,
      using water concentration as an exposure estimate can introduce misclassification
      of exposure for DBPs whose primary route is ingestion due to the great
      variability in the amount of water ingested across a population.

PMID- 9924005
TI  - Use of the Caco-2 cell model to assess the relative lead-chelating ability of
      diasterioisomers of 2,3-dimercaptosuccinic acid.
AB  - The purpose of this study was to examine the mechanisms of lead (Pb) uptake by
      human intestinal cells and to compare the intestinal transport and relative lead
      chelating ability of two diastereoisomeric forms (i.e., meso and racemic) of 2, 3
      dimercaptosuccinic acid (DMSA). The model used was the human adenocarcinoma (Caco
      2) cell monolayer. The Caco-2 cells were cultured in flasks for examination of
      cellular uptake of lead and subsequent chelation of the lead by the DMSA isomers.
      For assessment of the comparative intestinal transport of the diastereoisomers,
      the Caco-2 cells were cultured on semipermeable supports. The effects of N
      ethylmaleimide and 1,25-dihydroxyvitamin D3 (vitamin D3) on the uptake of lead by
      the Caco-2 monolayer were examined to determine the contributions of sulfhydryl
      binding and calcium-binding protein, respectively, to the lead uptake process.
      Analysis of lead was performed using both macro- and micro-proton-induced X-ray
      emission (PIXE), and DMSA was measured spectrophotometrically following
      derivatization with 5,5'-dithiobis-2-nitrobenzoic acid. Results from micro-PIXE
      imaging suggest that lead is bound on the surface of the cell, and that
      sulfhydryl binding may be an important step in the uptake of lead by the Caco-2
      cells. Macro-PIXE results indicate that the racemic form of DMSA may be more
      effective in chelating lead from within the cell. Comparison of the transport of
      the two DMSA diastereoisomers indicates that the racemic form is transported
      across the Caco-2 monolayer more readily than the meso form.

PMID- 9924006
TI  - Acute gastrointestinal effects of graded levels of copper in drinking water.
AB  - The objective of this study was to determine the acute gastrointestinal effects
      caused by the consumption of drinking water containing graded levels of added
      copper. Sixty healthy, adult women were randomly assigned to receive copper
      [Cu(II)] at four concentrations in their drinking water following a Latin-square
      design. Each group (n = 15) received tap water with no added copper, 1, 3, and 5
      mg Cu/l of added copper sulfate for a 2-week study period, followed by 1 week of
      standard tap water. The subjects recorded their water consumption and
      gastrointestinal symptoms daily on a special form. The average daily consumption
      of water was 1.64 liters per subject, regardless of the amount of copper added.
      Final serum copper, ceruloplasmin, and liver enzymes were measured in all
      subjects and were not different from baseline concentrations. Twenty-one subjects
      (35%) recorded gastrointestinal disturbances sometime during the study, 9 had
      diarrhea, some with abdominal pain and vomiting, and 12 subjects presented
      abdominal pain, nausea, or vomiting. There was no association between copper
      levels in drinking water and diarrhea. However, nausea, abdominal pain, or
      vomiting were significantly related to copper concentrations in water. The
      recorded incidence rate of these symptoms was 5, 2, 17, and 15% while ingesting
      water with 0, 1, 3, and 5 mg Cu/l, respectively (overall [chi]2 = 11.3, p<0.01;
      Cu [less than/equal to]1 mg/l versus Cu [Greater than/equal to]3 mg/l, [chi]2,
      p<0.01). When subjects interrupted their consumption of drinking water with added
      copper, most symptoms disappeared. We conclude that under the conditions of the
      study, there was no association between aggregate copper in drinking water within
      the range of 0-5 mg/l and diarrhea, but a [Greater than/equal to]3 mg Cu/l level
      of ionized copper was associated with nausea, abdominal pain, or vomiting.
      Additional studies with sufficient numbers of subjects are needed to define
      thresholds for specific gastrointestinal symptoms with precision and to
      extrapolate these results to the population at large.

PMID- 9924007
TI  - Exposure to atmospheric radon.
AB  - We measured radon (222Rn) concentrations in Iowa and Minnesota and found that
      unusually high annual average radon concentrations occur outdoors in portions of
      central North America. In some areas, outdoor concentrations exceed the national
      average indoor radon concentration. The general spatial patterns of outdoor radon
      and indoor radon are similar to the spatial distribution of radon progeny in the
      soil. Outdoor radon exposure in this region can be a substantial fraction of an
      individual's total radon exposure and is highly variable across the population.
      Estimated lifetime effective dose equivalents for the women participants in a
      radon-related lung cancer study varied by a factor of two at the median dose, 8
      mSv, and ranged up to 60 mSv (6 rem). Failure to include these doses can reduce
      the statistical power of epidemiologic studies that examine the lung cancer risk
      associated with residential radon exposure.

PMID- 9924008
TI  - Relationship between allergic contact dermatitis and electrophilicity.
AB  - To evaluate the role of electrophilicity in the induction of allergic contact
      dermatitis (ACD) in humans, we compared the structure-activity relationship (SAR)
      model of ACD with those of electrophilic and nonelectrophilic subsets of
      chemicals in the ACD database. For these analyses, electrophilicity was defined
      as the potential of a chemical to induce mutations in Salmonella. It was found
      that electrophilicity accounted for approximately 30-40% of ACD-inducing ability,
      and the remainder was associated with nonelectrophilic structures. The
      identification of these moieties opens the possibility for studying their role in
      ACD.

PMID- 9924009
TI  - Customer exposure to MTBE, TAME, C6 alkyl methyl ethers, and benzene during
      gasoline refueling.
AB  - We studied customer exposure during refueling by collecting air samples from
      customers' breathing zone. The measurements were carried out during 4 days in
      summer 1996 at two Finnish self-service gasoline stations with "stage I" vapor
      recovery systems. The 95-RON (research octane number) gasoline contained
      approximately 2.7% methyl tert-butyl ether (MTBE), approximately 8.5% tert-amyl
      methyl ether (TAME), approximately 3.2% C6 alkyl methyl ethers (C6 AMEs), and
      0.75% benzene. The individual exposure concentrations showed a wide log-normal
      distribution, with low exposures being the most frequent. In over 90% of the
      samples, the concentration of MTBE was higher (range <0.02-51 mg/m3) than that of
      TAME. The MTBE values were well below the short-term (15 min) threshold limits
      set for occupational exposure (250-360 mg/m3). At station A, the geometric mean
      concentrations in individual samples were 3.9 mg/m3 MTBE and 2. 2 mg/m3 TAME. The
      corresponding values at station B were 2.4 and 1.7 mg/m3, respectively. The
      average refueling (sampling) time was 63 sec at station A and 74 sec at station
      B. No statistically significant difference was observed in customer exposures
      between the two service stations. The overall geometric means (n = 167) for an
      adjusted 1-min refueling time were 3.3 mg/m3 MTBE and 1.9 mg/m3 TAME. Each day an
      integrated breathing zone sample was also collected, corresponding to an
      arithmetic mean of 20-21 refuelings. The overall arithmetic mean concentrations
      in the integrated samples (n = 8) were 0.90 mg/m3 for benzene and 0.56 mg/m3 for
      C6 AMEs calculated as a group. Mean MTBE concentrations in ambient air (a
      stationary point in the middle of the pump island) were 0.16 mg/m3 for station A
      and 0.07 mg/m3 for station B. The mean ambient concentrations of TAME, C6 AMEs,
      and benzene were 0.031 mg/m3, approximately 0.005 mg/m3, and approximately 0.01
      mg/m3, respectively, at both stations. The mean wind speed was 1.4 m/sec and mean
      air temperature was 21 degreesC. Of the gasoline refueled during the study, 75%
      was 95 grade and 25% was 98/99 grade, with an oxygenate (MTBE) content of 12.2%.

PMID- 9924010
TI  - Reproductive and morphological condition of wild mink (Mustela vison) and river
      otters (Lutra canadensis) in relation to chlorinated hydrocarbon contamination.
AB  - We assessed chlorinated hydrocarbon contamination of mink and river otters on the
      Columbia and Fraser River systems of northwestern North America, in relation to
      morphological measures of condition. We obtained carcasses of mink and river
      otters from commercial trappers during the winters 1994-1995 and 1995-1996.
      Necropsies included evaluation of the following biological parameters: sex, body
      mass and length, age, thymus, heart, liver, lung, spleen, pancreas, kidney,
      gonad, omentum, adrenal gland and baculum masses, baculum length, and stomach
      contents. Livers were analyzed, individually or in pools, for residues of
      organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), dibenzo-p
      dioxins, and dibenzofurans. Contaminant levels were relatively low compared to
      those documented in other North American populations, although they ranged higher
      than those detected during an earlier survey (1990-1992) of these regional
      populations. Body condition varied slightly among collection regions, but showed
      no relationship with contaminant burden. Mink from the upper Fraser River had
      less fat stores and also had some of the lowest OC contamination levels observed.
      Similarly, a few individuals with enlarged livers and kidneys had low contaminant
      levels. Although a few individual animals with gross abnormalities of
      reproductive systems did not show high levels of contamination, there was a
      significant negative correlation between total PCB concentrations (as Aroclor
      1260) and baculum length in juvenile mink (r = 0.707; p = 0.033; n = 8). The
      association of juvenile baculum length with eventual reproductive success is
      unknown, but further characterization of reproductive organ morphology and
      relationship to contaminants should be undertaken in a larger subset of these
      populations.

PMID- 9924011
TI  - Air pollution and daily mortality in Seoul and Ulsan, Korea.
AB  - The relationship between air pollution and daily mortality for the period 1991
      1995 was examined in two Korean cities, Seoul and Ulsan. The observed
      concentrations of sulfur dioxide (SO2; mean = 28.7 ppb), ozone (O3; mean = 29.2
      ppb), and total suspended particulates (TSP; mean = 82.3 microg/m3) during the
      study period were at levels below Korea's current ambient air quality standards.
      Daily death counts were regressed separately in the two cities, using Poisson
      regression on SO2, O3, and/or TSP controlling for variability in the weather and
      seasons. When considered singly in Poisson regression models controlling for
      seasonal variations and weather conditions, the nonaccidental mortality
      associated with a 50-ppb increment in a 3-day moving average of SO2
      concentrations, including the concurrent day and the preceding 2 days, was 1.078
      [95% confidence interval (CI), 1.057-1.099] for Seoul and 1.051 (CI, 0.991-1.115)
      for Ulsan. The rate ratio was 1.051 (CI, 1.031-1.072) in Seoul and 0.999 (CI, 0.
      961-1.039) in Ulsan per 100 microg/m3 for TSP, and 1.015 (CI, 1. 005-1.025) in
      Seoul and 1.020 (0.889-1.170) in Ulsan per 50 ppb for 1-hr maximum O3. When TSP
      was considered simultaneously with other pollutants, the TSP association was no
      longer significant. We observed independent pollution effects on daily mortality
      even after using various approaches to control for either weather or seasonal
      variables in the regression model. This study demonstrated increased mortality
      associated with air pollution at both SO2 and O3 levels below the current World
      Health Organization recommendations.

PMID- 9924013
TI  - Cyclosiloxanes produce fatal liver and lung damage in mice.
AB  - To examine the toxicity of cyclosiloxanes (CSs), the predominant low molecular
      weight cyclic silicones found in breast implants, we injected female CD-1 mice
      intraperitoneally with different doses of distillate (3.5-35 g/kg body weight)
      containing cyclosiloxane D3 (hexamethylcyclotrisiloxane; CS-D3), cyclosiloxane D4
      (octamethylcyclotetrasiloxane; CS-D4), cyclosiloxane D5
      (decamethylcyclopentasiloxane; CS-D5), and cyclosiloxane D6
      (dodecamethylcyclohexasiloxane; CS-D6). The distillate was found to be lethal and
      all the mice injected with 35 g/kg died within 5-8 days. The median lethal dose
      (LD50) for distillate was estimated to be approximately 28 g/kg. These mice
      developed inflammatory lesions of the lung and liver as well as liver cell
      necrosis with elevated serum levels of alanine aminotransferase, aspartate
      aminotransferase, and lactic acid dehydrogenase. Administration of CS-D4 alone
      also produced lethality in these mice with an LD50 of 6-7 g/kg. CS-D4-treated
      mice also exhibited pulmonary and hepatic lesions and elevated serum enzymes.
      Analysis of LD50 data indicates that CS-D4 is about as toxic as carbon
      tetrachloride or trichloroethylene. We measured hydroxyl radical formation in CS
      D4-treated mice and found increases of approximately 20-fold in liver and
      approximately 7-fold in lung on day 4 following injection. Our findings are
      significant because in vitro experiments have demonstrated that CSs can migrate
      out of breast implants, and in mouse experiments CSs have been shown to be widely
      distributed in many organs after a single subcutaneous injection and to persist
      for at least a year.

PMID- 9924012
TI  - No threshold dose for estradiol-induced sex reversal of turtle embryos: how
      little is too much?
AB  - Risk assessments for nongenotoxic chemicals assume a threshold below which no
      adverse outcomes are seen. However, when an endogenous chemical, such as 17ss
      estradiol (E2), occurs at a concentration sufficient to cause an effect, the
      threshold is already exceeded. Under these circumstances, exogenous estradiol is
      not expected to provide a threshold dose. This principle is demonstrated for E2
      in the red-eared slider, a turtle with temperature-dependent sex determination.
      In this species, gonadal sex is determined by egg incubation temperature; female
      development requires endogenous estrogen produced by elevated temperature. While
      normal production of females by endogenous estrogens is not an adverse effect,
      exogenous estrogens can sex reverse presumptive males, which can be an adverse
      effect. A large dose-response study was conducted using seven doses and a vehicle
      control (starting n = 300/group); a single E2 dose was applied to the eggshell of
      recently laid eggs. Animals were sexed after hatching. The incubation temperature
      chosen, 28.6 degrees C, generates a minority of females. Thus, the criteria for
      testing the threshold hypothesis were met, i.e., there is evidence that there is
      endogenous estrogen and that it generates an irreversible response. The lowest E2
      dose tested, 400 pg/egg (40 ng/kg), sex reversed 14.4% of the animals,
      demonstrating very low dose sensitivity. The data were fit with a modified
      Michaelis-Menten equation, which provided an estimate of 1.7 ng/egg for
      endogenous estradiol. The median effective dose (ED50) was 5.0 +/- 2.0 ng/egg
      (95% confidence limits), of which 1.7 ng/egg was endogenous estradiol and 3.3
      ng/egg came from the applied estradiol. There was no apparent threshold dose for
      E2. A smaller replication confirmed these results. These results provide a simple
      biologically based dose-response model and suggest that chemicals which act
      mechanistically like E2 may also show no threshold dose. If so, even low
      environmental concentrations of such chemicals may carry risk for sex reversal.

PMID- 9924014
TI  - Absence of certainty is not synonymous with absence of risk.

PMID- 9924015
TI  - Complex cleanup.

PMID- 9924016
TI  - Environmental casualties of the war on drugs.

PMID- 9924017
TI  - MicroCAT & mouse.

PMID- 9924019
TI  - "Dip-Pen" nanolithography 
AB  - A direct-write "dip-pen" nanolithography (DPN) has been developed to deliver
      collections of molecules in a positive printing mode. An atomic force microscope
      (AFM) tip is used to write alkanethiols with 30-nanometer linewidth resolution on
      a gold thin film in a manner analogous to that of a dip pen. Molecules are
      delivered from the AFM tip to a solid substrate of interest via capillary
      transport, making DPN a potentially useful tool for creating and functionalizing
      nanoscale devices.

PMID- 9924018
TI  - Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase
      complexes.
AB  - The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways
      by many receptors coupled to heterotrimeric guanine nucleotide binding proteins
      (G proteins) requires the activation of Src family tyrosine kinases. Stimulation
      of beta2 adrenergic receptors resulted in the assembly of a protein complex
      containing activated c-Src and the receptor. Src recruitment was mediated by beta
      arrestin, which functions as an adapter protein, binding both c-Src and the
      agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src
      binding or in the ability to target receptors to clathrin-coated pits, acted as
      dominant negative inhibitors of beta2 adrenergic receptor-mediated activation of
      the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding,
      which terminates receptor-G protein coupling, also initiates a second wave of
      signal transduction in which the "desensitized" receptor functions as a critical
      structural component of a mitogenic signaling complex.

PMID- 9924020
TI  - Visible quantum cutting in LiGdF4:Eu3+ through downconversion 
AB  - For mercury-free fluorescent lamps and plasma display panels, alternative
      luminescent materials are required for the efficient conversion of vacuum
      ultraviolet radiation to visible light. Quantum cutting involving the emission of
      two visible photons for each vacuum ultraviolet photon absorbed is demonstrated
      in Eu3+-doped LiGdF4 with the concept of downconversion. Upon excitation of Gd3+
      with a high-energy photon, two visible photons can be emitted by Eu3+ through an
      efficient two-step energy transfer from Gd3+ to Eu3+, with a quantum efficiency
      that approaches 200 percent.

PMID- 9924021
TI  - Argon-lead isotopic correlation in mid-atlantic ridge basalts 
AB  - Step-heating analyses for Mid-Atlantic Ridge glass samples show that maximum
      40Ar/36Ar values correlate with 206,207,208Pb/204Pb. These correlations hold for
      the whole Atlantic Ocean and therefore are unlikely to result from shallow-level
      contamination processes. Instead, they are taken as mixing hyperbolae between the
      degassed-depleted upper mantle and a recycled component characterized by high
      206Pb/204Pb ratios (19 to 21) and low 40Ar/36Ar ratios (300 to 1000). These
      relations imply that argon may also be a tracer of mantle recycling.

PMID- 9924022
TI  - Electrical conductivity in the precambrian lithosphere of western canada 
AB  - The subcrustal lithosphere underlying the southern Archean Churchill Province
      (ACP) in western Canada is at least one order of magnitude more electrically
      conductive than the lithosphere beneath adjacent Paleoproterozoic crust. The
      measured electrical properties of the lithosphere underlying most of the
      Paleoproterozoic crust can be explained by the conductivity of olivine. Mantle
      xenolith and geological mapping evidence indicate that the lithosphere beneath
      the southern ACP was substantially modified as a result of being trapped between
      two nearly synchronous Paleoproterozoic subduction zones. Tectonically induced
      metasomatism thus may have enhanced the subcrustal lithosphere conductivity of
      the southern ACP.

PMID- 9924023
TI  - Continental drainage in north america during the phanerozoic from Nd isotopes 
AB  - Neodymium (Nd) isotopic data show consistent patterns in the sources of
      sedimentary rocks in North America at a continental scale. Between 600 and 450
      million years ago (Ma), ancient continental shield sources dominated. Around 450
      Ma, detritus from the Caledonian-Appalachian mountains overwhelmed sediment from
      all older sources, and is documented over large areas of the southern, western,
      and northern margins of North America. This material continued to dominate the
      sediment supply until about 150 Ma, probably due to cannibalistic recycling of
      sedimentary rocks formed earlier. Around 150 Ma, the rising western Cordillera
      delivered new and different detritus to the sedimentary system.

PMID- 9924024
TI  - 13C-Depleted carbon microparticles in >3700-Ma sea-floor sedimentary rocks from
      west greenland 
AB  - Turbiditic and pelagic sedimentary rocks from the Isua supracrustal belt in west
      Greenland [more than 3700 million years ago (Ma)] contain reduced carbon that is
      likely biogenic. The carbon is present as 2- to 5-micrometer graphite globules
      and has an isotopic composition of delta13C that is about -19 per mil (Pee Dee
      belemnite standard). These data and the mode of occurrence indicate that the
      reduced carbon represents biogenic detritus, which was perhaps derived from
      planktonic organisms.

PMID- 9924025
TI  - Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC.
AB  - The protein encoded by the c-MYC proto-oncogene is a transcription factor that
      can both activate and repress the expression of target genes, but few of its
      transcriptional targets have been identified. Here, c-MYC is shown to repress the
      expression of the heavy subunit of the protein ferritin (H-ferritin), which
      sequesters intracellular iron, and to stimulate the expression of the iron
      regulatory protein-2 (IRP2), which increases the intracellular iron pool. Down
      regulation of the expression of H-ferritin gene was required for cell
      transformation by c-MYC. These results indicate that c-MYC coordinately regulates
      genes controlling intracellular iron concentrations and that this function is
      essential for the control of cell proliferation and transformation by c-MYC.

PMID- 9924026
TI  - T lymphocyte costimulation mediated by reorganization of membrane microdomains.
AB  - Although dispensable, costimulation through CD28 facilitates activation of naive
      T lymphocytes. CD28 engagement led to the redistribution and clustering of
      membrane and intracellular kinase-rich raft microdomains at the site of T cell
      receptor (TCR) engagements. Although not affecting TCR down-regulation, this
      process led to higher and more stable tyrosine phosphorylation of several
      substrates and higher consumption of Lck. These results may provide a general
      mechanism for amplifying receptor signaling by reorganization of membrane
      microdomains.

PMID- 9924027
TI  - Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID
      mice by HIV vectors.
AB  - Efficient gene transfer into human hematopoietic stem cells (HSCs) is an
      important goal in the study of the hematopoietic system as well as for gene
      therapy of hematopoietic disorders. A lentiviral vector based on the human
      immunodeficiency virus (HIV) was able to transduce human CD34+ cells capable of
      stable, long-term reconstitution of nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) mice. High-efficiency transduction occurred in the
      absence of cytokine stimulation and resulted in transgene expression in multiple
      lineages of human hematopoietic cells for up to 22 weeks after transplantation.

PMID- 9924028
TI  - Acetogenesis from H2 plus CO2 by spirochetes from termite guts.
AB  - Pure cultures of termite gut spirochetes were obtained and were shown to catalyze
      the synthesis of acetate from H2 plus CO2. The 16S ribosomal DNA sequences of two
      strains were 98 percent similar and were affiliated with those of the genus
      Treponema. However, neither was closely related to any known treponeme. These
      findings imply an important role for spirochetes in termite nutrition, help to
      reconcile the dominance of acetogenesis over methanogenesis as an H2 sink in
      termite hindguts, suggest that the motility of termite gut protozoa by means of
      attached spirochetes may be based on interspecies H2 transfer, and underscore the
      importance of termites as a rich reservoir of novel microbial diversity.

PMID- 9924029
TI  - Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive human disease associated with multiple deletions of skeletal muscle
      mitochondrial DNA (mtDNA), which have been ascribed to a defect in communication
      between the nuclear and mitochondrial genomes. Examination of 12 MNGIE probands
      revealed homozygous or compound-heterozygous mutations in the gene specifying
      thymidine phosphorylase (TP), located on chromosome 22q13.32-qter. TP activity in
      leukocytes from MNGIE patients was less than 5 percent of controls, indicating
      that loss-of-function mutations in TP cause the disease. The pathogenic mechanism
      may be related to aberrant thymidine metabolism, leading to impaired replication
      or maintenance of mtDNA, or both.

PMID- 9924030
TI  - Immortal time: circadian clock properties of rat suprachiasmatic cell lines.
AB  - Cell lines derived from the rat suprachiasmatic nucleus (SCN) were screened for
      circadian clock properties distinctive of the SCN in situ. Immortalized SCN cells
      generated robust rhythms in uptake of the metabolic marker 2-deoxyglucose and in
      their content of neurotrophins. The phase relationship between these rhythms in
      vitro was identical to that exhibited by the SCN in vivo. Transplantation of SCN
      cell lines, but not mesencephalic or fibroblast lines, restored the circadian
      activity rhythm in arrhythmic, SCN-lesioned rats. Thus, distinctive oscillator,
      pacemaker, and clock properties of the SCN are not only retained but also
      maintained in an appropriate circadian phase relationship by immortalized SCN
      progenitors.

PMID- 9924031
TI  - Horizontal propagation of visual activity in the synaptic integration field of
      area 17 neurons.
AB  - The receptive field of a visual neuron is classically defined as the region of
      space (or retina) where a visual stimulus evokes a change in its firing activity.
      At the cortical level, a challenging issue concerns the roles of feedforward,
      local recurrent, intracortical, and cortico-cortical feedback connectivity in
      receptive field properties. Intracellular recordings in cat area 17 showed that
      the visually evoked synaptic integration field extends over a much larger area
      than that established on the basis of spike activity. Synaptic depolarizing
      responses to stimuli flashed at increasing distances from the center of the
      receptive field decreased in strength, whereas their onset latency increased.
      These findings suggest that subthreshold responses in the unresponsive region
      surrounding the classical discharge field result from the integration of visual
      activation waves spread by slowly conducting horizontal axons within primary
      visual cortex.

PMID- 9924032
TI  - Chemical etiology of nucleic acid structure: comparing pentopyranosyl-(2'-->4')
      oligonucleotides with RNA.
AB  - All four members of the family of pentopyranosyl-(2'-->4') oligonucleotide
      systems that contain beta-ribo-, beta-xylo-, alpha-lyxo-, or alpha
      arabinopyranosyl units as repeating sugar building blocks are found to be much
      stronger Watson-Crick base-pairing systems than RNA. The alpha-arabinopyranosyl
      system is the strongest of all and in fact belongs to the strongest
      oligonucleotide base-pairing systems known. Whatever the chemical determinants by
      which nature selected RNA as a genetic system, maximization of base-pairing
      strengths within the domain of pentose-derived oligonucleotide systems was not
      the critical selection criterion.

PMID- 9924033
TI  - Reduced immunotoxicity and preservation of antibacterial activity in a releasable
      side-chain carbapenem antibiotic.
AB  - A carbapenem antibiotic, L-786,392, was designed so that the side chain that
      provides high-affinity binding to the penicillin-binding proteins responsible for
      bacterial resistance was also the structural basis for ameliorating
      immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring
      retained antibacterial activity while safely expelling the immunodominant
      epitope. L-786,392 was well tolerated in animal safety studies and had
      significant in vitro and in vivo activities against methicillin- and vancomycin
      resistant Staphylococci and vancomycin-resistant Enterococci.

PMID- 9924034
TI  - Viagra: a botched test case for rationing.

PMID- 9924035
TI  - Gulf war syndrome.

PMID- 9924036
TI  - What urologists say they do for men with prostate cancer.

PMID- 9924037
TI  - Patients' priorities.

PMID- 9924038
TI  - Elder abuse.

PMID- 9924040
TI  - In brief 

PMID- 9924039
TI  - UK issues guidance on prescribing Viagra.

PMID- 9924041
TI  - Clinton offers healthcare funding ideas.

PMID- 9924042
TI  - Researchers discover how opiates cause immunosuppression 

PMID- 9924043
TI  - Fibre does not protect against colon cancer 

PMID- 9924044
TI  - College plans help for children in war zones 

PMID- 9924046
TI  - GPs criticised by ombudsman.

PMID- 9924045
TI  - Doctors may report violence to police.

PMID- 9924047
TI  - Adult stem cells may be redefinable 

PMID- 9924048
TI  - BMA warns of arrival of genetic weapons.

PMID- 9924049
TI  - Inquiry calls for checks on staff who work with elderly.

PMID- 9924050
TI  - Bristol inquiry appoints doctor to its panel.

PMID- 9924051
TI  - The man from SMAC.

PMID- 9924052
TI  - Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial
      with six year follow up.
AB  - OBJECTIVE: To evaluate the efficacy of using a nicotine patch for 5 months with a
      nicotine nasal spray for 1 year. DESIGN: Placebo controlled, double blind trial.
      SETTING: Reykjavik health centre. SUBJECTS: 237 smokers aged 22-66 years living
      in or around Reykjavik. INTERVENTIONS: Nicotine patch for 5 months with nicotine
      nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119).
      Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the
      fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray
      was available for up to 1 year. Both groups received supportive treatment. MAIN
      OUTCOME MEASURE: Sustained abstinence from smoking. RESULTS: Sustained abstinence
      rates for the patch and nasal spray group and patch only group were 51% v 35%
      after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32;
      P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16%
      after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03,
      1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08)
      [corrected]. CONCLUSIONS: Short and long term abstinence rates show that the
      combination of using a nicotine patch for 5 months with a nicotine nasal spray
      for 1 year is a more effective method of stopping smoking than using a patch
      only. The low percentage of participants using the nasal spray at 1 year, and the
      few relapses during the second year, suggest that it is not cost effective to use
      a nasal spray for longer than 7 months after stopping a patch.

PMID- 9924053
TI  - Clinical findings for the first 1000 Gulf war veterans in the Ministry of
      Defence's medical assessment programme.
AB  - OBJECTIVE: To review the clinical findings in the first 1000 veterans seen in the
      Ministry of Defence's Gulf war medical assessment programme to examine whether
      there was a particular illness related to service in the Gulf. DESIGN: Case
      series of 1000 veterans who presented to the programme between 11 October 1993
      and 24 February 1997. SUBJECTS: Gulf war veterans. MAIN OUTCOME MEASURES:
      Diagnosis of veterans' conditions according to ICD-10 (international
      classification of diseases, 10th revision). Cases referred for psychiatric
      assessment were reviewed for available diagnostic information from consultant
      psychiatrists. RESULTS: 588 (59%) veterans had more than one diagnosed condition,
      387 (39%) had at least one condition for which no firm somatic or psychological
      diagnosis could be given, and in 90 (9%) veterans no other main diagnosis was
      made. Conditions characterised by fatigue were found in 239 (24%) of patients. At
      least 190 (19%) patients had a psychiatric condition, which in over half was due
      to post-traumatic stress disorder. Musculoskeletal disorders and respiratory
      conditions were also found to be relatively common (in 182 (18%) and 155 (16%)
      patients respectively). CONCLUSION: Many Gulf war veterans had a wide variety of
      symptoms. This initial review shows no evidence of a single illness,
      psychological or physical, to explain the pattern of symptoms seen in veterans in
      the assessment programme. As the veterans assessed by the programme were all self
      selected, the prevalence of illness in Gulf war veterans cannot be determined
      from this study. Furthermore, it is not known whether the veterans in this study
      were representative of sick veterans as a group.

PMID- 9924054
TI  - Current status of long term ventilation of children in the United Kingdom:
      questionnaire survey.
AB  - OBJECTIVES: To identify the number and current location of children, aged 0 to 16
      years, requiring long term ventilation in the United Kingdom, and to establish
      their underlying diagnoses and ventilatory needs. DESIGN: Postal questionnaires
      sent to consultant respiratory paediatricians and all lead clinicians of
      intensive care and special care baby units in the United Kingdom. SUBJECTS: All
      children in the United Kingdom who, when medically stable, continue to need a
      mechanical aid for breathing. RESULTS: 141 children requiring long term
      ventilation were identified from the initial questionnaire. Detailed information
      was then obtained on 136 children from 30 units. Thirty three children (24%)
      required continuous positive pressure ventilation by tracheostomy over 24 hours,
      and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%),
      tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying
      conditions included neuromuscular disease (n=62; 46%), congenital central
      hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial
      syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25;
      18%). 93 children were cared for at home. 43 children remained in hospital
      because of home circumstances, inadequate funding, or lack of provision of home
      carers. 96 children were of school age and 43 were attending mainstream school.
      CONCLUSIONS: A significant increase in the number of children requiring long term
      ventilation in the United Kingdom has occurred over the past decade. Contributing
      factors include improved technology, developments in paediatric non-invasive
      ventilatory support, and a change in attitude towards home care. Successful
      discharge home and return to school is occurring even for severely disabled
      patients. Funding and home carers are common obstacles to discharge.

PMID- 9924055
TI  - Dilemmas in treating early prostate cancer: the evidence and a questionnaire
      survey of consultant urologists in the United Kingdom.

PMID- 9924056
TI  - What it's all about 

PMID- 9924058
TI  - The difference 

PMID- 9924057
TI  - Privacy, dignity, and confidentiality: interview study with structured
      questionnaire.

PMID- 9924059
TI  - Prevalence of anxiety and depressive illness and help seeking behaviour in
      African Caribbeans and white Europeans: two phase general population survey.
AB  - OBJECTIVE: To determine the prevalence of common mental disorders (anxiety and
      depression) and help seeking behaviour in African Caribbeans and white Europeans.
      DESIGN: Two phase survey in a general population sample. The first phase
      comprised screening with the 12 item general health questionnaire; the second
      phase was standardised psychiatric assessment and interview about help seeking.
      SETTING: People registered with four general practices in central Manchester.
      PARTICIPANTS: Of 1467 people randomly selected from family health services
      authority lists, 864 were still resident. 337 African Caribbeans and 275 white
      Europeans completed the screening phase (response rate 71%); 127 African
      Caribbeans and 103 white Europeans were interviewed in the second phase. MAIN
      OUTCOME MEASURES: One month period prevalence of anxiety and depressive disorders
      in each ethnic group. RESULTS: 13% of African Caribbeans (95% confidence interval
      10% to 16%) and 14% (10% to 18%) of white Europeans had one or more disorder.
      Anxiety disorders were significantly less common among African Caribbeans (3% (1%
      to 5%) v 9% (6% to 12%) in white Europeans). Depressive disorders were
      significantly more common among African Caribbean women than white women
      (difference 8% (1% to 15%)). Medical help seeking was similar in the two groups,
      but African Caribbeans with mental disorders were more likely to seek additional
      help from non-medical sources (12/29 v 5/29, P=0.082). CONCLUSIONS: In an inner
      city setting the prevalence of common mental disorders is similar in these two
      ethnic groups.

PMID- 9924060
TI  - Retrospective analysis of census data on general practitioners who qualified in
      South Asia: who will replace them as they retire?
AB  - OBJECTIVES: To determine the number and geographical distribution of general
      practitioners in the NHS who qualified medically in South Asia and to project
      their numbers as they retire. DESIGN: Retrospective analysis of yearly data and
      projection of future trends. SETTING: England and Wales. SUBJECTS: General
      practitioners who qualified medically in the countries of Bangladesh, India,
      Pakistan, and Sri Lanka and who were practising in the NHS on 1 October 1992.
      MAIN OUTCOME MEASURES: Proportion and age of general practitioners who qualified
      in South Asia by health authority; the Benzeval and Judge measure of population
      need at the health authority level. RESULTS: 4192 of 25 333 (16.5%) of all
      unrestricted general practitioners practising full time on 1 October 1992
      qualified in South Asian medical schools. The proportion varied by health
      authority from 0.007% to 56.5%. Roughly two thirds who were practising in 1992
      will have retired by 2007; in some health authorities this will represent a loss
      of one in four general practitioners. The practices that these doctors will leave
      seem to be in relatively deprived areas as measured by deprivation payments and a
      health authority measure of population need. CONCLUSION: Many general
      practitioners who qualified in South Asian medical schools will retire within the
      next decade. The impact will vary greatly by health authority. Those health
      authorities with the greatest number of such doctors are in some of the most
      deprived areas in the United Kingdom and have experienced the most difficulty in
      filling vacancies. Various responses will be required by workforce planners to
      mitigate the impact of these retirements.

PMID- 9924062
TI  - New Year's Eve 

PMID- 9924061
TI  - Science, medicine, and the future: Parkinson's disease.

PMID- 9924063
TI  - ABC of sexual health: assessing and managing male sexual problems.

PMID- 9924064
TI  - Sharing decisions with patients: is the information good enough?

PMID- 9924066
TI  - On seeing a kangaroo 

PMID- 9924065
TI  - Narrative based medicine: narrative based medicine in an evidence based world.

PMID- 9924067
TI  - Deprivation and emergency admissions for cancers. Other possible explanations for
      findings need to be explored.

PMID- 9924069
TI  - Bulimic eating patterns should be stabilised in polycystic ovarian syndrome.

PMID- 9924068
TI  - Effect of flutamide on survival in patients with pancreatic cancer. Study needs
      to be repeated on a much larger scale.

PMID- 9924070
TI  - Wrist watches must be removed before washing hands.

PMID- 9924071
TI  - Intravenous beta blockade in acute myocardial infarction. Doubts exist about
      external validity of trials of intravenous beta blockade.

PMID- 9924072
TI  - Storing methadone in babies' bottles puts young children at risk.

PMID- 9924073
TI  - Standards in advertising. Has Didronel PMO been proved to protect against
      osteoporosis?

PMID- 9924074
TI  - Intensive cognitive behaviour therapy for chronic schizophrenia. Specific effect
      of cognitive behaviour therapy for schizophrenia is not proved.

PMID- 9924075
TI  - Implementing research findings in developing countries. Skills for appraising
      evidence must be taught.

PMID- 9924076
TI  - Using research findings in clinical practice. Doctors advocating evidence based
      medicine may be out of touch with real medicine.

PMID- 9924077
TI  - Safety of genetically engineered foods is still dubious.

PMID- 9924078
TI  - Sir geoffrey bateman 

PMID- 9924079
TI  - Steps needed to solve NHS workforce problems 

PMID- 9924080
TI  - BMA's annual meeting 

PMID- 9924081
TI  - A season in hell 

PMID- 9924082
TI  - Dobson's complaint: the story of the chester porphyria 

PMID- 9924083
TI  - Partners of the heart 

PMID- 9924084
TI  - Textbook of clinical medicine for asia 

PMID- 9924085
TI  - Viagra, rationed 

PMID- 9924087
TI  - The sharp edge of damocles 

PMID- 9924086
TI  - Website of the week 

PMID- 9924089
TI  - A big week 

PMID- 9924088
TI  - Science night 

PMID- 9924090
TI  - Nicotine nasal spray with patch is effective in stopping smoking 

PMID- 9924092
TI  - More children are being ventilated long term 

PMID- 9924091
TI  - No single illness explains pattern of symptoms in gulf war veterans 

PMID- 9924094
TI  - Depression is common in african caribbeans in UK inner cities 

PMID- 9924093
TI  - Privacy and dignity are lacking on children's wards 

PMID- 9924095
TI  - Retirement of asian GPs will cause problems for recruitment 

PMID- 9924096
TI  - Spinal anticipation and cortical correction: coordination of movements (1930).

PMID- 9924097
TI  - What does EMG tell us about muscle function?
AB  - EMG recordings are frequently used to obtain a better understanding in the
      coordination of movements. However, EMG is made up by the weighted summation of
      activity of many motor units with different contractile properties. Recent
      studies have revealed that different motor units contribute to muscle force in
      different motor tasks. The flexible recruitment of motor units with various
      contractile properties allows a flexible tuning of muscle properties, but also
      complicates the interpretation of EMG activity.

PMID- 9924098
TI  - Patterns of center of presure migration during prolonged unconstrained standing.
AB  - Prolonged (>30 min) unconstrained standing (PUS) was studied in 10 young healthy
      subjects. The usual methods of stabilographic analysis assume a random center of
      pressure (COP) migration. This study was based on the opposite idea and showed
      that during PUS, specific and consistent patterns of the COP migration can be
      recognized by a computer algorithm. Three COP migration patterns were found: (a)
      shifting, a fast displacement of the average position of COP from one region to
      another; (b) fidgeting, a fast and large displacement and returning of COP to
      approximately the same position; and (c) drifting, a slow continuous displacement
      of the average position of COP. A software code was written and default parameter
      values were chosen for recognizing COP migration patterns. For 30-min PUS the
      following patterns were identified: Shifting was generally observed every 316 +/-
      292 sec in the anterior-posterior (a-p) direction with an average shift amplitude
      of 17 +/- 15 mm, and every 199 +/- 148 sec in the medial-lateral (m-l) direction
      with an average shift amplitude of 22 +/- 38 mm. Corresponding time intervals for
      fidgeting were 59 +/- 15 sec in the a-p direction and 49 +/- 16 sec in the m-l
      direction. The average drift-to-drift interval was 319 +/- 173 sec in the a-p
      direction and 529 +/- 333 sec in the m-l direction.

PMID- 9924099
TI  - Instant equilibrium point and its migration in standing tasks: rambling and
      trembling components of the stabilogram.
AB  - A method of decomposing stabilograms into two components, termed rambling, was
      developed. The rambling component reveals the motion of a moving reference point
      with respect to which the body's equilibrium is instantly maintained. The
      trembling component reflects body oscillation around the reference point
      trajectory. The concepts of instant equilibrium point (IEP) and discrete IEP
      trajectory are introduced. The rambling trajectory was computed by interpolating
      the discrete IEP trajectory with cubic spline functions. The trembling trajectory
      is found as a difference between the approximated rambling trajectory and the COP
      trajectory. Instant values of the horizontal ground reaction force at a zero time
      lag. It suggests that trembling is strongly influenced by a restoring force
      proportional to the magnitude of COP deviation from the rambling trajectory and
      acts without a time delay. An increment in relative COP position per unit of the
      restoring force in mm/N, was on average 1.4 +/- 0.4. The contribution of rambling
      and trembling components in the stabilogram was ascertained. The rambling
      variability is approximately three times larger than the trembling variability.

PMID- 9924100
TI  - Structural constraints on the coordination of concurrent rotations of the head
      and a steering device.
AB  - Concurrent movements of different effectors are subject to structural constraints
      that facilitate certain patterns of coordination but impede others. The
      constraints for concurrent rotations of the head and a bimanually operated
      steering device were explored in two experiments. To indicate structural
      constraints, the difference between concurrent periodic rotations in same and
      different directions with respect to the variable error of synchronization was
      used. The first experiment showed less error for rotations in same directions
      than for rotations in opposite directions. In the second experiment, the same
      result was obtained with a horizontal and a backward-tilted steering wheel.
      Adding gaze shifts to head oscillations increased the accuracy of synchronization
      but did not affect the difference between both coordination patterns. In contrast
      to the synchronization of head and steering device, the variable error of
      synchronization of gaze and steering wheel did not differ between both modes of
      coordination; the error was again reduced when head oscillations were added to
      the saccades between eccentric fixation targets. This suggests space related (or
      allocentric) constraints, which most likely originate from concurrent
      specifications of movement directions in coupled spatiotopic maps so that the
      specification of rotations in the same direction is facilitated in comparison to
      rotations in opposite directions.

PMID- 9924102
TI  - Magnetic Effect on Ion-Exchange Kinetics.
AB  - Effects of magnetic exposure on an ion-exchange process are investigated,
      employing ion-exchange resins. The electrolyte solution, resin suspension, and
      water are mixed in a container, and the mass transfer coefficient is determined
      by measuring the change of the ionic concentration in the bulk. Two methods of
      magnetic exposure are performed: case (1) in which only the electrolyte solution
      is exposed to the magnetic field and case (2) in which only the resin suspension
      is exposed to the magnetic field. The following features are found in both cases:
      (i) the film mass transfer rate reduces by about 5% when the exposure time is
      greater than 25 min, (ii) the magnetic effect is reduced by adding the alcohol,
      (iii) the magnetic effect remains for about 3 days but disappears after 6 days,
      and (iv) the magnetic effect is observable in the solutions of structure
      disordering ions, but not in the solutions of structure-ordering ions. As for the
      temperature dependence, the magnetic effect decreases with temperature in case
      (1) but it stays constant in case (2). It is postulated that the magnetic effects
      are attributable to the stabilization of water molecules around the structure
      ordering ion and those on the resin surface. Copyright 1999 Academic Press.

PMID- 9924101
TI  - The role of ErbB receptor signaling in cell fate decisions by cortical
      progenitors: evidence for a biased, lineage-based responsiveness to different
      ligands.
AB  - We recently identified the required collaborative signaling of TGFalpha and
      collagen type IV to regulate cell fate choice in the cerebral cortex, measured by
      the expression of the limbic system associated membrane protein (LAMP) by
      nonlimbic, sensorimotor progenitors. We show that activation of different members
      of the erbB receptor family can similarly modulate the specification of cortical
      area fate. The region of the cerebral wall from which progenitor cells arise does
      not influence the response to the neuregulin-1 or TGFalpha, but a subpopulation
      of progenitors is not competent to express LAMP in response to neuregulin-1. The
      heterogeneity in the responsiveness by progenitors to the two growth factors is
      reflected in the expression of different repertoires of erbB receptors. Using
      clonal analysis, we demonstrate that there may be a lineage-dependent mechanism
      regulating the ability of neuronal progenitors to respond to specific inductive
      cues that control cell fate.

PMID- 9924103
TI  - Aggregation Behavior of Tyloxapol, a Nonionic Surfactant Oligomer, in Aqueous
      Solution.
AB  - The aggregation behavior of Tyloxapol, a nonionic surfactant oligomer with a
      repeating unit close to Triton X-100 (TX100), and a maximum degree of
      polymerization of about 7, has been investigated in aqueous solution by means of
      fluorescence probing, time-resolved fluorescence quenching (TRFQ) and
      transmission electron microscopy at cryogenic temperature (cryo-TEM). The plot of
      the pyrene fluorescence intensity ratio I1/I3 against the Tyloxapol concentration
      shows no clear evidence of a critical micelle concentration contrary to TX100.
      Nevertheless, the fitting of these data, assuming a partition of pyrene between
      Tyloxapol aggregates and water, yields cmc values in the micromolar range, i.e.,
      about a hundred times lower than for the "monomer" TX100. The values of I1/I3 at
      high surfactant concentrations indicate that Tyloxapol micelles provide pyrene a
      less polar environment than TX100 micelles. The use of the viscosity-sensitive
      probe 1,3-dipyrenylpropane indicates that the microviscosity of Tyloxapol
      micelles is quite high, three to four times larger than that for TX100 micelles,
      and decreases rapidly with increasing temperature. Also the microviscosities of
      both TX100 and Tyloxapol micelles are larger than those for the micelles of the
      nonionic ethoxylated surfactant C12E9. The aggregation numbers of Tyloxapol and
      of TX100 micelles measured using TRFQ increase with temperature, with the
      Tyloxapol micelles being smaller than the TX100 micelles. Cryo-TEM shows that the
      Tyloxapol micelles remain spheroidal up to a concentration of about 10 wt%. At 15
      wt%, some regions of ordered elongated micelles are also observed which may be
      the precursors of the hexagonal phase known to occur at about 35 wt%. Copyright
      1999 Academic Press.

PMID- 9924104
TI  - Surface Science of a Filled Polydimethylsiloxane-Based Alkoxysilane-Cured
      Elastomer: RTV11.
AB  - Characterization of a filled polydimethylsiloxane (PDMS)-based elastomer, RTV11,
      is reported. Included in this work is resin characterization, kinetics of cure as
      a function of catalyst concentration, and surface properties of pristine and
      water-aged films. X-ray spectroscopy for chemical analysis (ESCA), dynamic
      contact angle (DCA) analysis, and ATR-IR were used to characterize cured films.
      ESCA reveals C and Si peaks in ratios expected for PDMS, but CaCO3 which
      comprises 32% of the bulk is not detected. The surface of cured RTV11 films is
      thus predominantly a PDMS network crosslinked by a siliceous domain, the latter
      comprising about 1.3% by weight. The presence of Ca was confirmed by energy
      dispersive X-ray analysis (EDX) which probes at micron depth. Stability of films
      in water was evaluated by tapping mode atomic force microscopy (TM-AFM), mass
      loss, changes in contact angles, ESCA, and optical microscopy. TM-AFM images of
      films aged in water for three months show an increase in surface roughness due to
      the formation of micro-pits which occupy about 4% of the surface. Gravimetric
      analysis showed fully cured films lose mass at a rate of about 0.09%/wk over a
      three month period in water. The mass loss associated with pitting/surface
      roughening comprises only 0.85% of that measured gravimetrically and by analysis
      of immersion water. Analysis of Si and Ca in the storage water was performed by
      inductively coupled plasma atomic emission spectroscopy (ICP-AES) in order to
      quantify the products of surface erosion. An unexpected finding was the surface
      depletion-limited loss of CaCO3 during the first two months of immersion. The
      results of surface analytical studies are discussed in the context of the use of
      alkoxysilane cured PDMS resins for nontoxic fouling release applications.
      Copyright 1999 Academic Press.

PMID- 9924105
TI  - Effect of Block and Graft Copolymers on the Stability of Colloidal Silica.
AB  - We use dynamic light scattering to measure the time-dependent increase of the
      average hydrodynamic radius of colloidal silica particles in the presence of
      salt. This increase appears to be linear in time up to twice the radius of
      unaggregated particles. The method is a very useful tool in monitoring the
      stabilizing effect of adsorbed polymers. Four different series of diblock and
      graft copolymers were used to stabilize an aqueous silica dispersion against
      aggregation by salt. For two series of nonselectively adsorbing diblock
      copolymers with relatively low adsorbed amounts, we found a clear correlation
      between the adsorbed amount and the stabilization: a higher adsorbed amount leads
      to slower aggregation and thus provides a better stabilization. This is
      rationalized in terms of retarded bridge formation. Excellent steric
      stabilization was obtained with a series of amphiphilic diblock copolymers and
      with two graft copolymers. All these polymers produce adsorbed layers with a
      clear "anchor-buoy" structure, either due to selective solvency (amphiphilic
      diblocks) or selective adsorption (graft copolymers). Such layers cannot form
      bridges so that the layers are purely repulsive. Copyright 1999 Academic Press.

PMID- 9924106
TI  - A Model for Metal Adsorption on Montmorillonite.
AB  - A consistent thermodynamic model is developed for metal sorption on expanding 2:1
      layer clays such as montmorillonite. The particle of clay, including lamellae and
      interlayers, is represented as a porous solid bearing a permanent negative charge
      (resulting from isomorphic substitution) with an infinite plane interface (i.e.,
      edges) with the solution. Cation exchange occurs inside the clay particle as the
      result of the negative potential of the clay. Surface complexation reactions take
      place at the interface whose surface charge and potential are pH dependent. The
      potential in the bulk of the clay and near the interface, as well as the surface
      potential-surface charge density relation, are calculated taking into account the
      effect of the permanent negative charge. The results are discussed and compared
      with the classic Gouy-Chapman theory. A subroutine (Clayeql) with the new
      potential-charge relationships is implemented in the thermodynamic equilibrium
      program Mineql +3.0 and is used to fit an extensive published experimental data
      set on adsorption of transition metals on montmorillonite. The model is shown not
      only to fit satisfactorily all the data, but also to explain specific features of
      adsorption on clays compared to oxides. In particular, the increase in the
      surface concentration of protons with decreasing ionic strength is successfully
      reproduced and the weaker dependence of metal sorption on pH compared to oxides
      is correctly fitted. Copyright 1999 Academic Press.

PMID- 9924107
TI  - Kinetics and Mechanism of Two-Electron Reduction of Surfacial Ferric Ions of
      Colloidal Ferrofluid by l-Ascorbic Acid in Aqueous Acidic Medium.
AB  - The kinetics of electron transfer from l-ascorbic acid (H2A) to ferrofluid (FF)
      in dilute aqueous acidic solutions (pH 2.5-4.0) was investigated
      spectrophotometrically in detail as a function of [H2A], [FF], [H+], ionic
      strength, and temperature. FF was found to be reduced and the reduction was first
      order dependent on both H2A and FF concentrations. An inverse first order
      dependence in H+ ion concentration and no dependence on ionic strength were
      observed. Kinetic, electrochemical, spectrophotometric, and thermodynamic results
      are interpreted in terms of a mechanism involving a rate-determining outer-sphere
      one-electron transfer from H2A to FF followed by a subsequent and kinetically
      rapid transfer of the second electron of H2A to the same molecule of FF, which
      was already reduced by one electron in rate-determining step. This overall two
      electron transfer process from H2A to the same molecule of FF is discussed and
      compared with other closely related reactions. Copyright 1999 Academic Press.

PMID- 9924108
TI  - Influence of Oxygen Plasma Treatment of PAN-Based Carbon Fibers on Their
      Electrokinetic and Wetting Properties.
AB  - Oxygen plasma treatment was used to modify the surfaces of high-tenacity
      polyacrylonitrile-based carbon fibers. Changes in the surface composition of
      plasma-treated fibers were investigated by electrokinetic (zeta-potential)
      measurements as well as by wetting studies to evaluate the solid surface tension.
      Treating carbon fibers in an oxygen plasma results in an increased surface
      acidity, as can be seen from the overall shape of the zeta = f(pH) function and
      from the shift of the isoelectric points toward lower pH. The increased surface
      polarity improves the wetting behavior versus water. Although the fibers become
      more hydrophilic, the adsorption of ions from the electrolyte solution, which
      should compete with water adsorption, increases. Almost no changes in the surface
      morphology could be monitored by scanning electron microscopy. However, wetting
      and zeta-potential measurements confirm changes at the fiber surface. zeta
      Potential measurements and wetting (contact angle) measurements complement each
      other. This allows observation of changes taking place in the surface chemistry
      after modifications applied to industrially available unmodified carbon fibers.
      Copyright 1999 Academic Press.

PMID- 9924109
TI  - The Effect of Membrane Charge on Gold Nanoparticle Synthesis via Surfactant
      Membranes.
AB  - The effect of vesicle membrane structure and charge on the synthesis of gold
      nanoparticles was investigated. The vesicle membranes were comprised of either
      negatively charged soy lipids or mixtures of charge neutral and negatively
      charged soy lipids. Palladium ions bound to the membranes served as the catalyst
      for metal particle synthesis using an electroless metallization procedure. The
      size range of particles synthesized using membranes comprised of only negatively
      charged lipids (5-15 nm) was significantly smaller than those synthesized using
      mixtures of negatively charged and charge-neutral lipids (2-180 nm). X-ray
      diffraction revealed that the average crystallite size decreased with increasing
      palladium ion content of the membranes. It also showed that the average
      crystallite size was smaller for particles synthesized using vesicles comprised
      of only soy phoshohydroxyethanol lipids than for particles synthesized using
      vesicles comprised of only soy phosphatidic acid lipids. Particles synthesized
      with membranes comprised of only negatively charged lipids were encapsulated
      within the resulting lipid membrane matrix. FT-IR of the lipid matrix indicated
      that the matrix was formed as the result of ionic bridging of the lipid phosphate
      headgroups with gold ions. Copyright 1999 Academic Press.

PMID- 9924110
TI  - Simultaneous In-Situ Measurement of Local Particle Size, Particle Concentration,
      and Velocity of Aerosols.
AB  - Photon correlation spectroscopy has been applied to the characterization of
      (quasi-)monodisperse aerosols. The experiments were carried out with an
      experimental standard pin hole setup on laminar flowing aerosols of the
      submicrometer particle size range. It is shown that beside local mean particle
      size and local aerosol velocity simultaneously the local particle number
      concentration may be obtained from a single measured autocorrelation function.
      The proposed procedure does not require calibration. It is pointed out that
      measurement conditions can be adapted to the properties of the aerosol to be
      characterized, thus allowing characterization of aerosols over a wide parameter
      range, e.g., it is not restricted to the case of low particle concentration. The
      experimental results are compared to data from literature, data from reference
      measurements and data from a theoretical model, respectively. The method can also
      be usefull for characterization of other fluid-particle systems as hydrosols.
      Copyright 1999 Academic Press.

PMID- 9924111
TI  - Thermodynamics of Micellization of Surfactants of Low Aggregation Number: The
      Aggregation of Propranolol Hydrochloride.
AB  - The self-association of propranolol hydrochloride in aqueous solution has been
      studied as a function of temperature. The critical concentration (C*) and the
      degree of ionization (alpha) were determined by conductivity measurements at
      temperatures over the range 298.15 to 313.15 K. The enthalpy change on
      aggregation in water was measured by microcalorimetry. To calculate changes in
      the thermodynamic properties of aggregation the mass action model for high and
      low aggregation numbers was applied, the latter model giving better agreement
      between experimental and theoretical enthalpy changes. Copyright 1999 Academic
      Press.

PMID- 9924112
TI  - Nonlinear Stability of an Electrified Interface Supporting Surface Charges
      between Two Viscous Fluids.
AB  - The charged boundary between two viscous fluid media is taken to be under the
      influence of a vertical constant electric field producing surface charges. We
      illustrate the solution of the nonlinear perturbation using the method of
      multiple scales. In the neutral stability the relation between surface charge
      density and surface viscous force is obtained. Because the viscosity ratio has
      the same value as the dielectric constant ratio a singularity in the nonlinear
      coefficient of Schrodinger equation is observed and gradually creates a growth in
      the instability. Previous works have failed to recognize this singularity by not
      including the effects of viscosity. The absence of surface viscous force leads to
      decay in the surface charge density and a growth in the stability occurs. Global
      stability and local instability are observed in the stability diagrams. The
      duality mechanism is observed for the electric field, the surface charge density,
      and the stratified kinematic viscosity. Further, the behavior away from neutral
      stability is explained by examination of the dynamical system. It is observed
      that the stabilizing or destabilizing role for the surface charge density has
      been related to the destabilizing or stabilizing role of the density influence.
      Copyright 1999 Academic Press.

PMID- 9924113
TI  - The Effect of Cholesterol on the Solution Structure of Proteins of Photosystem
      II. Protein Secondary Structure and Photosynthetic Oxygen Evolution.
AB  - Cholesterol induces large perturbations in the physical properties of membranes,
      especially in the structural organization of the phospholipid bilayers and the
      aggregation and solubility of proteins at physiological temperatures. This study
      was designed to examine the interaction of cholesterol with lipid and proteins of
      chloroplasts photosystem II (PSII) submembrane fractions in air dried film at pH
      6-7 with cholesterol concentrations of 0.01 to 20 mM. Fourier transform infrared
      difference spectroscopy with its self-deconvolution and second derivative methods
      as well as curve-fitting procedures are used, in order to determine the
      cholesterol binding mode, the protein conformational changes, and the structural
      properties of cholesterol-protein complexes. Correlations between the effect of
      cholesterol on the protein secondary structure and the rate of oxygen evolution
      in PSII are also established. Spectroscopic evidence showed that at low
      cholesterol concentration (0.01 and 0.1 mM), minor chol-protein and chol-lipid
      interactions (through hydrogen bonding) occur with no major perturbations of the
      protein secondary structure. As cholesterol concentration increases (5 and 10 and
      20 mM), major alterations of the protein secondary structure are observed from
      that of the alpha-helix 47% (uncomplexed protein) to 43-39% (complexes) and the
      beta-sheet structure 18% (uncomplexed protein) to 22-26% (complexes). Those
      changes coincide with a partial decrease in the rate of the oxygen evolution (8
      33%) is observed in the presence of cholesterol at high concentration. Copyright
      1999 Academic Press.

PMID- 9924114
TI  - Preparation of Palladium Ultrafine Particles in Reverse Micelles.
AB  - The preparation of palladium ultrafine particles by the reduction of Pd(NH3)4Cl2
      with hydrazine in AOT/isooctane reverse micellar solutions has been studied. By
      the analyses of high-resolution electron microscope, electron diffraction
      pattern, and XRD, the resultant particles have been found to be pure fcc
      palladium. Their sizes were observed to increase first and then approach constant
      values with increases in the molar ratio of water to AOT (omega0) and in the
      concentration of Pd(NH3)4Cl2, but were not significantly affected when the
      concentration ratio of hydrazine to Pd(NH3)4Cl2 was above 10, the AOT
      concentration increased from 0.1 to 1.0 M, the temperature varied from 15 to 35
      degreesC, and the pH of aqueous phase of Pd(NH3)4Cl2 was between 7 and 12. In
      addition, the kinetic study of particle formation indicated that the nucleation
      time needed several minutes. After nucleation, the particles grew to their final
      sizes within several to tens of minutes. The formation rates were found to be
      faster at larger omega0 values and higher AOT and Pd(NH3)4Cl2 concentrations.
      Copyright 1999 Academic Press.

PMID- 9924115
TI  - Studies on Indian Ocean Manganese Nodules.
AB  - The effects of alkali (sodium hydroxide) treatment on the physico-chemical
      properties and catalytic activity for H2O2 decomposition and CO oxidation of
      Indian Ocean manganese nodules have been studied. The surface area, surface
      oxygen, surface hydroxyl groups, etc. increase with alkali treatment up to 0.05 M
      and there after show a decreasing trend. The high catalytic activity of 0.05 M
      NaOH treated samples are correlated with the surface properties. Copyright 1999
      Academic Press.

PMID- 9924116
TI  - Adsorption Mechanism of Conventional and Dimeric Cationic Surfactants on Silica
      Surface: Effect of the State of the Surface.
AB  - The aim of this study was to investigate the effect of the state of the silica
      surface and of the surfactant molecular structure on the adsorption of cationic
      surfactants onto silica. Thus, the adsorption of DTAB (dodecyltrimethylammonium
      bromide) and of the dimeric surfactant 12-2-12 (ethanediyl-1,2
      bis(dodecyldimethylammonium bromide)) on raw silica (SiNa) and on HCl-washed
      silica (SiH) has been investigated under "free" system conditions. The amount of
      surfactant adsorbed (adsorption isotherm), the sodium ion and bromide ion
      concentrations and the pH in the equilibrated supernatant, and the silica
      particle electrophoretic mobility have been measured along the isotherms. The
      adsorption mechanisms of the two surfactants on the raw and washed silica are
      qualitatively similar. Nevertheless, important quantitative differences are
      observed which are all due to (i) the larger number of surface sites present at
      the surface of SiNa with respect to SiH and (ii) the larger ionic strength of the
      supernatant in SiNa/surfactant systems with respect to SiH/surfactant systems,
      due to the much larger amount of sodium ions released by SiNa upon surfactant
      binding. Thus, the amounts of surfactant adsorbed at the point of zero charge and
      at saturation of the silica particles, of sodium ions released by the surface and
      the decrease of critical micelle concentration (cmc) in the supernatant with
      respect to pure water are all larger for the raw silica than for the treated
      silica. For the four silica/surfactant systems investigated, the first adsorption
      step corresponds to the adsorption of individual surfactant ions on the negative
      sites of the silica surface. It is driven by electrostatic interactions and
      strongly dependent on the number of surface sites and ionic strength associated
      to the released ions. At the end of the first adsorption step, which is clearly
      seen with SiH/surfactant systems, the second adsorption step starts. This step is
      driven by hydrophobic interaction between surfactant alkyl chains and results in
      the formation of surface aggregates. The surfactant adsorption on the surface is
      shown to continue even after the cmc in the supernatant is reached. Copyright
      1999 Academic Press.

PMID- 9924117
TI  - The Interfacial Tension between Acrylic Monomers and Polymers and Non-ionic
      Surfactants Investigated by the Automatic Sessile Drop Method.
AB  - Time dependent interfacial tensions between CCl4, butyl acrylate (BA), and methyl
      methacrylate (MMA) and water have been measured, using nine different aryl and
      alkyl poly(oxyethylene) surfactants with between 10 and 40 OE-groups. The effect
      of adding BA/MMA and BA/MMA/acrylic acid (AA) polymers to the monomer systems has
      also been evaluated. In all systems the interfacial tension, after a very fast
      initial drop, decreases slowly due to dissolution of the surfactant inside the
      oil. The magnitude of this decrease is dependent on the hydrophilicity of the
      surfactant and the oil. The equilibrium values, when plotted against the HLB of
      the surfactants show a minimum that shifts toward higher HLB as the oil's
      polarity increases. BA and CCl4 show similar behavior, but with MMA as a more
      polar oil. Added polymer generally lowers the time dependent decrease because of
      decreased surfactant solubility in monomer/polymer mixtures. The BA/MMA copolymer
      also generally increases the interfacial tension both with and without
      surfactants, but the increase is less with surfactants around the surface tension
      minimum. A BA/MMA/AA terpolymer neutralizes or even reverses the increasing
      effect in the BA/polymer system because of this polymer's more hydrophilic
      nature. Copyright 1999 Academic Press.

PMID- 9924118
TI  - The Dependence of the Apparent Contact Angles on Gravity.
AB  - We have studied theoretically the effect of gravity on the rough solid-liquid
      interface and have shown that its tension is enhanced by gravity when gas is
      adsorbed at it. As a result, the apparent contact angle on rough surfaces, which
      has been considered not to be influenced by gravity so far, can be raised by
      gravity. The calculated dependence of contact angles on gravity under the
      ordinary conditions of the sessile drop method is large enough to detect by
      experiment. The observed asymmetrical deviations from Wenzel's contact angle
      caused by the gas adsorption at the solid-liquid interface and by the liquid
      adsorption at the solid-gas interface are explained in terms of this
      gravitational effect. Copyright 1999 Academic Press.

PMID- 9924119
TI  - Orogenic Displacement of Protein from the Air/Water Interface by Competitive
      Adsorption.
AB  - The displacement of proteins from an air/water interface by surfactant has been
      visualized by atomic force microscopy (AFM) through the imaging of Langmuir
      Blodgett films formed on mica. Three different proteins were studied: beta
      casein, a largely random coil protein, and two globular proteins, beta
      lactoglobulin and alpha-lactalbumin. The proteins were displaced from both spread
      and coadsorbed films using the nonionic surfactant Tween 20. The combined use of
      AFM with studies of surface tension and surface rheology have revealed the
      mechanism of protein desorption from the air/water interface. The surfactant is
      found to adsorb at defects in the protein network and these nucleated sites then
      grow, compressing the protein network. At sufficiently high surface pressures the
      network fails, releasing proteins that then desorb from the interface. We have
      called this mechanism orogenic displacement. Stress propagation through beta
      casein films is homogeneous resulting in the growth of circular surfactant
      domains. beta-Lactoglobulin and alpha-lactalbumin form stronger networks and
      stress propagation is restricted resulting in the growth of irregular (fractal)
      surfactant domains. The AFM images also provide direct evidence for the formation
      of elastic (gel-like) protein networks at the air/water interface. Copyright 1999
      Academic Press.

PMID- 9924120
TI  - Surface Area Evaluation of Montmorillonite.
AB  - Adsorption of molecules of different sizes on montmorillonite and on hydroxy-Al
      montmorillonite was studied to examine the effect of sorbate size on the
      experimental value of the surface area of the clays. For each clay the number of
      adsorbate units at the adsorption maximum per gram of clay produces a single
      hyperbolic curve, when plotted as a function of the area occupied by adsorbate,
      in the range of areas of 22-180 A2 per sorbate. The equations of the curves are:
      N A = 657.7 m2/g for the clay and N A = 202.8 A0.27 for the hydroxy-Al
      montmorillonite. A dependence of the surface area of the hydroxy-Al
      montmorillonite on adsorbate size was observed and was attributed to surface
      irregularities produced by hydroxy-Al interlayering. Copyright 1999 Academic
      Press.

PMID- 9924121
TI  - Simultaneous Determination of Surface Tension and Density of Polymer Melts Using
      Axisymmetric Drop Shape Analysis.
AB  - By employing a new strategy, we show that axisymmetric drop shape analysis (ADSA)
      can be used to determine simultaneously the surface tension and the density of
      polymer melts from sessile drops at elevated temperatures. To achieve this, two
      developments were necessary. First, the ADSA algorithm had to be modified to
      replace the density by the mass of the drop as an input parameter. Since ADSA
      also yields the volume, the density became output rather than input. Second, a
      closed high-temperature chamber whose temperature could be precisely controlled
      and a sample holder that allowed the formation of highly axisymmetric sessile
      drops at elevated temperatures had to be developed. For a typical polymeric
      material (polystyrene), it is demonstrated that measurements with sessile drops
      yield essentially the same surface tension values and temperature coefficients as
      measurements with pendant drops. The densities determined with ADSA are
      comparable to independent PVT results. Copyright 1999 Academic Press.

PMID- 9924122
TI  - Surface Structural Ion Adsorption Modeling of Competitive Binding of Oxyanions by
      Metal (Hydr)oxides.
AB  - Spectroscopy has provided a progressive flow of information concerning the
      binding mechanism(s) of ions and their surface-complex structure. An important
      challenge in surface complexation models (SCM) is to connect the molecular
      microscopic reality to macroscopic adsorption phenomena. This is important
      because SCM alone provide insufficient insight in the binding mechanisms, and
      moreover, it is a priori not obvious that SCM, which describe the pH dependent
      adsorption correctly in simple systems, will predict the ion interaction under
      multicomponent conditions. This study elucidates the primary factor controlling
      the adsorption process by analysing the adsorption and competition of PO4, AsO4,
      and SeO3. We show that the structure of the surface-complex acting in the
      dominant electrostatic field can be ascertained as the primary controlling
      adsorption factor. The surface species of arsenate are identical with those of
      phosphate and the adsorption behavior is very similar. On the basis of the
      selenite adsorption, we show that the commonly used 2pK models are incapable to
      incorporate in the adsorption modeling the correct bidentate binding mechanism
      found by spectroscopy. The use of the bidentate mechanism leads to a proton
      oxyanion ratio and corresponding pH dependency that are too large. The
      inappropriate intrinsic charge attribution to the primary surface groups and the
      condensation of the inner sphere surface complex to a point charge are
      responsible for this behavior of commonly used 2pK models. Both key factors are
      differently defined in the charge distributed multi site complexation (CD-MUSIC)
      model and are based in this model on a surface structural approach. The CD-MUSIC
      model can successfully describe the macroscopic adsorption phenomena using the
      surface speciation and binding mechanisms as found by spectroscopy. The model is
      also able to predict the anion competition well. The charge distribution in the
      interface is in agreement with the observed structure of surface complexes.
      Copyright 1999 Academic Press.

PMID- 9924123
TI  - Dielectric Dispersion of Colloidal Suspensions in the Presence of Stern Layer
      Conductance: Particle Size Effects.
AB  - In this work, we discuss the role that particle size plays in the manifestations
      of surface conduction on the dielectric response of colloidal dispersions. To
      that aim, experimental data on the dielectric constant of polystyrene suspensions
      of two different particle diameters (23 and 530 nm) are first compared to the
      predictions of a classical or standard model (E. H. B. DeLacey and L. R. White,
      J. Chem. Soc. Faraday Trans. 2 77, 2007 (1983)), and it is found that, while the
      latter explains reasonably the dielectric behavior of the smallest particles, it
      considerably underestimates the phenomenon in the case of large particles. To
      explain these results in terms of contributions of ion motions in the inner
      region of the double layer of the particles, the approach followed by C. S.
      Mangelsdorf and L. R. White (J. Chem. Soc. Faraday Trans. 86, 2859 (1990)) is
      used to incorporate surface conductance in the theory of dielectric response of
      suspensions. In ac fields it is found that the model considerably improves the
      comparison between theory and experiment, whereas its use seems unnecessary for
      the smallest particles, where, whatever the combination used for the parameters
      of the theory, its predictions do not differ from the standard theory. Only in
      the case of the larger particles studied does the introduction of surface
      conductance play any role. A comparison between both types of theoretical results
      in a wide range of particle sizes demonstrates that Stern layer conductance
      always increases the magnitude of the low-frequency dielectric constant of
      suspensions, but its effect is less important the smaller the particle size and
      the larger the zeta potential for fixed ionic conditions in the dispersion
      medium. Copyright 1999 Academic Press.

PMID- 9924124
TI  - Comparative Studies of Carbon Blacks by Thermogravimetry and Nitrogen Adsorption.
AB  - Thermodesorption behavior of water, n-butanol, and n-heptane from different
      carbon blacks was studied by thermogravimetry. It was shown that differences in
      interactions of these adsorbates with the carbon blacks studied can be monitored
      by this technique. The adsorbates' polarity is essential in controlling
      thermodesorption from low surface area carbon blacks while this factor seems to
      be less important in the case of high surface area samples. The relative
      thermodesorption plot was introduced and used to analyze thermogravimetric data.
      It was shown that this method provides information about surface heterogeneity
      similar to that obtained from the comparative adsorption plot. In addition,
      thermogravimetric results are related to nitrogen adsorption data. Copyright 1999
      Academic Press.

PMID- 9924125
TI  - Covalent Modification of Emulsified beta-Casein Resulting from Lipid
      Peroxidation.
AB  - Competitive displacement of adsorbed protein from emulsion droplets by the
      surfactant Tween 20 has been used to determine the influence of the oil phase and
      aging on the behavior of beta-casein, the displaced protein being analyzed by
      reverse-phase high performance liquid chromatography HPLC. Unlike soluble beta
      casein or the protein displaced from tetradecane droplets where aging had no
      effect on the appearance of the HPLC profile, the protein displaced from a soya
      oil emulsion interface was observed to change. As the soya oil emulsion aged, the
      retention time of the protein decreased. Mass spectrometry of the modified
      protein showed that the molecular weight increased, indicating that some form of
      covalent modification was occurring. Gas chromatography-mass spectrometry of
      steam distillates of the samples showed the presence of a variety of aldehydes in
      microfluidized soya oil samples that were not present in either the original oil
      or the tetradecane emulsions. Aldehydes, particularly alpha,beta-unsaturated
      aldehydes (enals), which are the major components formed in these soya oil
      emulsions, are known to react with nucleophilic amino acid side chains such as
      lysine. This is the probable cause of the observed modification of the emulsified
      protein. These aldehydes, whose concentration increased with storage time, are
      formed by peroxidation of the unsaturated fatty acyl chains present in the soya
      oil as a result of the microfluidization process used in the preparation of the
      emulsions. The tryptic peptide pattern also changed with age due to modification
      of the primary structure of the protein. Potential consequences of these chemical
      changes arising as a result of microfluidization are discussed. Copyright 1999
      Academic Press.

PMID- 9924126
TI  - On the Possibility of Glue Contaminations in the Surface Force Apparatus.
AB  - A noninterferometric device has been employed to measure the surface forces
      between glass spheres. The aim was to investigate how the presence of a large
      area of the Epikote resin used with the surface force apparatus affects the
      interactions between clean glass spheres in pure water and in 10 mM NaCl.
      Copyright 1999 Academic Press.

PMID- 9924127
TI  - Preparation of Polymer-Stabilized Noble Metal Colloids.
AB  - A series of polymer-stabilized platinum and palladium colloids were prepared via
      methanol reduction for the investigation of the preparation conditions. Through
      TEM observation and catalytic hydrogenation of olefins, it was found that adding
      a suitable amount of NaOH was good for small-sized colloidal particles and higher
      catalytic hydrogenation activity. Copyright 1999 Academic Press.

PMID- 9924128
TI  - Emulsification through Area Contraction.
AB  - Emulsification requiring very little input energy can be induced at an oil-water
      interface that is initially in a state of equilibrium. The process involves
      destabilization, through contraction, of local interfacial regions. For
      emulsification to occur, it is necessary for the interfacial structure to have no
      resistance to surface shearing. Such a mechanism of emulsification may have
      important implications for the approach to solving emulsion problems in the
      petroleum industry. Copyright 1999 Academic Press.

PMID- 9924129
TI  - Density of Pure, Associating Fluids near the Solid-Liquid Interface.
AB  - In the present letter, we study the role of hydrogen bonds on the density of a
      pure, associating liquid in the solid-liquid interfacial region. The approach
      followed by us is to treat the liquid phase as comprising (i) oligomers/clusters
      of various sizes formed between the molecules of associating components present
      in the liquid/solid phases and (ii) holes. The interfacial properties of the
      resulting multicomponent system are then obtained using the monolayer theory
      proposed earlier by us (Suresh and Naik, 1996, 1997). The resulting expressions
      are found to be remarkably simple. To clearly demonstrate the accuracy of the
      proposed theory, results for the density of water-like molecules (each possessing
      two proton donor and two proton acceptor sites) near a hard wall are compared
      against those of available Monte-Carlo simulations (Segura and Chapman, 1995) and
      the density functional theory (Segura et al., 1997). Copyright 1999 Academic
      Press.

PMID- 9924130
TI  - Predictive Sagiv-Stroeve Model for Diffusion through Monolayer and Multilayer
      Films.
AB  - A one-parameter model has been derived by A. Sagiv and P. Stroeve for diffusion
      through crystalline monolayer and multilayer Langmuir-Blodgett films (J. Colloid
      Interface Sci. 204, 173 (1998)). The model can describe well a number of
      experimental observations. The parameter that is needed for the model, the
      activation rate constant (k), is obtained by fitting the experimental data. It is
      shown in this letter that the parameter can be calculated independently; hence,
      the model can be predictive. Examples for predictions are given. Copyright 1999
      Academic Press.

PMID- 9924131
TI  - Editorial announcement 

PMID- 9924132
TI  - Dental microwear of Griphopithecus alpani.
AB  - The examination of microscopic dental wear allows inferences to be made about
      diet in extinct species. This study reconstructs the diet of Griphopithecus
      alpani, a 15 Ma fossil hominoid from the Miocene site of Pasalar in north-western
      Turkey, using scanning electron microscopy (SEM) to examine the microscopic wear
      on its molar teeth. The microwear patterns of Griphopithecus are compared with
      those of three extant hominoid taxa-Gorilla gorilla gorilla, Pan troglodytes
      verus, and Pongo pygmaeus pygmaeus. The microwear on three occlusal wear surfaces
      is examined in this study, and sex and age differences are also included.
      Analysis of variance is performed on the following microwear variables-feature
      density, pit density, striation density, the ratio of pits relative to
      striations, pit widths, and striation widths. Griphopithecus has significantly
      higher microwear feature densities and higher percentages of pits than Gorilla.
      It also has larger pit frequencies and narrower striations than both Pan and
      Gorilla. There are no significant differences between the microwear patterns of
      Griphopithecus and Pongo. This suggests that the diet of Gripho-pithecus was more
      similar to that of Pongo, which consumes mainly fruit, and occasionally hard and
      unripe fruits and nuts, than to that of Pan and Gorilla. In addition, the high
      percentage of pits displayed by Griphopithecus may indicate that it was ingesting
      harder fruits and/or objects than the extant hominoids, although this is not a
      significant difference. There also are consistent variations in the microwear
      present on the three different wear facets examined in the study-Phase II facets
      display more microwear and pitting than the Phase I surface examined. The results
      of this study do not indicate variation in dental microwear according to sex or
      age.

PMID- 9924133
TI  - The quaternary cuban platyrrhine Paralouatta varonai and the origin of Antillean
      monkeys.
AB  - We describe recently recovered dental and mandibular remains of the Cuban
      platyrrhine Paralouatta varonai, previously known from the holotype only (a
      nearly complete skull with very worn teeth). We also expand on the original
      description of the type specimen. Paralouatta is one of three extinct taxa of
      Greater Antillean Quaternary monkeys known from craniodental remains. The other
      two, Xenothrix mcgregori and Antillothrix bernensis, occurred in Jamaica and
      Hispaniola, respectively. It has been common practice to assume that Antillean
      monkeys were more closely related to individual mainland taxa than to each other.
      Thus, P. varonai was thought to be related to Alouatta; Antillothrix bernensis to
      Saimiri or Cebus; and X. mcgregori to Callicebus, or to callitrichines, or even
      to be of unknown affinity. With the discovery of well-preserved dental remains of
      Paralouatta, it can now be ascertained that this species was in fact very
      different from Alouatta. Cladistic analysis reveals a sister-group relationship
      between Antillothrix and Paralouatta, followed on the cladogram by Xenothrix and
      Callicebus (last taxon being the closest mainlaind relative of the Antillean
      clade). This conclusion has an important biogeographic implication: recognition
      of an Antillean clade, as advocated here, assumes only one primate colonization
      from the South American mainland, not several as previously believed.

PMID- 9924134
TI  - South Turkwel: a new pliocene hominid site in Kenya.
AB  - New fossils discovered south of the Turkwel River in northern Kenya include an
      associated metacarpal, capitate, hamate, lunate, pedal phalanx, mandibular
      fragment, and teeth. These fossils probably date to around 3.5 m.y.a. Faunal
      information suggests that the environment at South Turkwel was predominantly
      bushland. The mandibular and dental remains are fragmentary, but the postcranial
      fossils are informative. Comparisons with Australopithecus, modern human,
      chimpanzee and gorilla hand bones suggest that the Turkwel hominid was most like
      Australopithecus afarensis and A. africanus. Carpometacarpal articulations are
      intermediate between those of modern humans and African apes, suggesting enhanced
      gripping capabilities compared with extant apes. The hamulus was strikingly
      large, similar in proportion only to Neandertals and some gorillas, suggesting
      the presence of powerful forearms and hands. There are no indicators of
      adaptations to knuckle-walking or suspensory locomotion in the hand, and the
      pedal phalanx suggests that this hominid was habitually bipedal.

PMID- 9924135
TI  - Nails and claws in primate evolution.
AB  - The issue of whether nails or claws were present on the digits of the last common
      ancestor of living primates is central to the understanding of the ecological
      context in which the order originated. Two lines of evidence are available, the
      shape (claw, nail, toilet-claw) and the histological structure (one or two horny
      strata). Here we review the existing data regarding the shape and histological
      structure of cheirideal appendages in primates and present new information from a
      wide range of living primates. We demonstrate the presence of a typical toilet
      claw in Daubentonia madagascariensis and discuss its consequences, since the
      alleged lack of such structures in this species has long obscured the issue. The
      general view that primate nails, with the exception of those in New World
      primates, consist of only one layer is disproved by the presence of two distinct
      strata in the nails of the feet of three out of seven catarrhine species
      examined, as well as in Lemur catta. The combined new and old data indicate that
      the last common ancestor of the extant primates had lost the typical mammalian
      claws of its ancestors and developed nails on all pedal digits except digit II,
      which bore a toilet-claw. All nails as well as the toilet-claw originally
      consisted of two layers. We present a new hypothesis regarding the adaptational
      significance of these changes.

PMID- 9924136
TI  - 'Homo rudolfensis' Alexeev, 1986-fact or phantom?

PMID- 9924137
TI  - Is "Homo rudolfensis" a valid species?

PMID- 9924138
TI  - Editorial Statement.

PMID- 9924139
TI  - A Structural Equation Model of the Effects of Negative Affectivity, Leader-Member
      Exchange, and Perceived Job Mobility on In-role and Extra-role Performance: A
      Chinese Case.
AB  - In this paper, we contrast the effects of leader-member exchange (LMX) with the
      effects of perceived job mobility on in-role performance and organizational
      citizenship behavior (OCB). We further model negative affectivity as the
      antecedent of both LMX and perceived job mobility and suggest that LMX and
      perceived job mobility mediated the relationship between negative affectivity and
      performance. We obtained matching data from supervisor and subordinates in a
      major battery manufacturing company in southern China. Subordinates provided the
      negative affectivity, perceived job mobility, and LMX assessment, and their
      immediate supervisors provided the in-role performance and OCB assessment.
      Results from a structural equation analysis show that both LMX and perceived job
      mobility predicted OCB. Instead of being a direct antecedent of OCB, the
      relationship between negative affectivity and OCB is found to be mediated by LMX
      and perceived job mobility. Theoretical implications of the results are
      discussed. Copyright 1999 Academic Press.

PMID- 9924140
TI  - Long and Short Routes to Success in Electronically Mediated Negotiations: Group
      Affiliations and Good Vibrations.
AB  - To understand why e-mail negotiations break down, we investigated two distinct
      elements of negotiators' relationships with each other: shared membership in a
      social group and mutual self-disclosure. In an experiment, some participants
      negotiated with a member of an outgroup (a student at a competitor university),
      whereas others negotiated with a member of an ingroup (a student at the same
      university). In addition, some negotiators exchanged personal information with
      their counterparts, whereas others did not. When neither common ingroup status
      nor a personalized relationship existed between negotiators, negotiations were
      more likely to end in impasse. These results are attributable to the positive
      influence of mutual self-disclosure and common group membership on negotiation
      processes and rapport between negotiators. Copyright 1999 Academic Press.

PMID- 9924141
TI  - Evidence against Rank-Dependent Utility Theories: Tests of Cumulative
      Independence, Interval Independence, Stochastic Dominance, and Transitivity.
AB  - This study tests between two modern theories of decision making. Rank- and sign
      dependent utility (RSDU) models, including cumulative prospect theory (CPT),
      imply stochastic dominance and two cumulative independence conditions. Configural
      weight models, with parameters estimated in previous research, predict systematic
      violations of these properties for certain choices. Experimental data
      systematically violate all three properties, contrary to RSDU but consistent with
      configural weight models. This study also tests whether violations of stochastic
      dominance can be explained by violations of transitivity. Violations of
      transitivity may be evidence of a dominance detecting mechanism. Although some
      transitivity violations were observed, most choice triads violated stochastic
      dominance without violating transitivity. Judged differences between gambles were
      not consistent with the CPT model. Data were not consistent with the editing
      principles of cancellation and combination. The main findings are interpreted in
      terms of coalescing, the principle that equal outcomes can be combined in a
      gamble by adding their probabilities. RSDU models imply coalescing but configural
      weight models violate it, allowing configural weighting to explain violations of
      stochastic dominance and cumulative independence. Copyright 1999 Academic Press.

PMID- 9924142
TI  - Naturally-occurring antisperm antibodies in men: interference with fertility and
      implications for treatment.
AB  - Naturally-occurring antisperm antibodies in men are a relative cause of
      infertility, being the fertility impairment related with the degree of sperm
      autoimmunization. The impairment of sperm penetration through the cervical mucus
      represents the best established mechanism of the antibody interference with
      fertility. Another mechanism may involve complement-mediated sperm injury and
      opsonizing effect through the female genital tract. Finally, sperm-bound
      antibodies can interfere with sperm functions involved in the fertilization
      process, mainly in the sperm-zona pellucida interaction. While some mechanisms of
      the antibody-interference with fertility depend only on the degree of sperm
      autoimmunization (e.g., inhibition of cervical mucus penetration), other
      mechanisms (e.g., interference with gametes interaction) could or could not occur
      depending on the relevance in the fertilization process of the specific
      antigen(s) recognized by antisperm antibodies, which are policlonal in nature.
      Intrauterine insemination is an effective treatment when sperm autoimmunization
      is low or moderate, mainly if combined with corticosteroid treatment and
      superovulated cycles. On the contrary, its effectiveness in cases of high degree
      of sperm autoimmunization is controversial. The resort to "high tech" procedures
      is mandatory when other less invasive approaches have failed or they may also be
      chosen as a first-choice method in cases of high degree of sperm
      autoimmunization. Since in most reports the fertilization rate with in vitro
      fertilization and embryo transfer (IVF-ET) was significantly lower in the
      presence of sperm-bound antibodies than in the case of other indications, the
      likelihood of fertilization is higher with intracytoplasmatic sperm injection
      (ICSI), where the reported fertilization rates are similar to those in other
      indications, or even higher.

PMID- 9924143
TI  - The chromosomal 2'-N-acetyltransferase of Providencia stuartii: physiological
      functions and genetic regulation.
AB  - Intrinsic chromosomal acetyltransferases involved in aminoglycoside resistance
      have been identified in a number of bacteria. In Providencia stuartii, a
      chromosomal acetyltransferase (AAC(2')-Ia) has been characterized in detail. In
      addition to the ability to acetylate aminoglycosides, the AAC(2')-Ia enzyme has
      at least one physiological function, which is the acetylation of peptidoglycan.
      This modification is likely to influence the autolytic system in P. stuartii. The
      regulation of aac(2')-Ia expression is extremely complex involving at least seven
      regulatory genes acting in at least two pathways. This complexity in regulation
      indicates that aac(2')-Ia expression must be tightly controlled in response to
      different environmental conditions. This presumably reflects the importance of
      maintaining correct levels of peptidoglycan acetylation. In this review, a
      summary of data will be presented involving both the physiological and genetic
      aspects of aac(2')-Ia in P. stuartii.

PMID- 9924144
TI  - Signal relays in the VEGF system.
AB  - A considerable progress has been made during the past years in elucidating the
      molecular actors of angiogenesis. Vascular endothelial growth factor turned out
      to represent the major inducer of angiogenesis. Optional splicing of its pre
      messenger RNA generates various isoforms which differ not only by their storage
      in the extracellular matrix but also by their signaling pathways. VEGF binds and
      activates two tyrosine kinase receptors called VEGFR1 and VEGFR2 and neuropilin
      1. The elucidation of the transduction pathways of each receptor suggests that
      VEGFR1 mediates cell migration whereas VEGFR2 mediates cell proliferation. The
      construction of internal images of VEGF by the anti-idiotypic antibody strategy
      allowed us to determine that quiescent endothelial cells need to be activated by
      so far unknown factors to become competent to respond to mitogenic signals and
      acquire an angiogenic phenotype. The discovery of the mechanisms of action of the
      VEGF system has allowed the design of promising drugs which already entered the
      pre-clinical or clinical assays.

PMID- 9924145
TI  - Nothin' but 'net?

PMID- 9924146
TI  - Myocardial necrosis in "pure unstable angina": identification of high-risk
      subgroups or a contradiction in terms?

PMID- 9924147
TI  - Treatment of diffuse coronary lesions: a time for randomized trials.

PMID- 9924148
TI  - Much ado about thrombin.

PMID- 9924149
TI  - Defining risk in unstable angina: current trial design does not tell us who
      should be treated and with what therapy.

PMID- 9924150
TI  - Diagnostic performance of cardiac troponin I in suspected acute myocardial
      infarction: implications for clinicians.

PMID- 9924151
TI  - Clinical implications of intravascular ultrasound imaging for stenting
      procedures.

PMID- 9924152
TI  - Understanding racial differences in the use of thrombolytic therapy: what more do
      we need to know?

PMID- 9924153
TI  - The enduring value of Killip classification.

PMID- 9924154
TI  - Infectious causes of atherosclerosis.

PMID- 9924155
TI  - Is all unstable angina the same? insights from the Coronary Angioplasty Versus
      Excisional Atherectomy Trial (CAVEAT-I). The CAVEAT-Investigators.
AB  - BACKGROUND: Certain characteristics of unstable angina have been associated with
      worse clinical outcomes after percutaneous revascularization procedures. METHODS
      AND RESULTS: We compared outcomes of patients with (n = 690) and those without (n
      = 320) unstable angina in the Coronary Angioplasty Versus Excisional Atherectomy
      Trial (CAVEAT-I) by unstable angina subgroup: rest chest pain, postinfarction
      chest pain, chest pain with ischemic electrocardiographic changes, chest pain
      with recent acceleration, and no chest pain. Regression models were constructed
      to predict in-hospital and 6-month composite end point death, infarction, bypass
      surgery, percutaneous revascularization, and abrupt closure (in-hospital) or
      restenosis (6 months) for each subgroup. Only chest pain with
      electrocardiographic changes predicted the composite in-hospital outcome (24% vs
      17% with no chest pain, P =.0374.) This subgroup also had a greater acute gain,
      more late loss, and more restenosis than patients in the other subgroups. Rest
      chest pain carried a higher incidence of the composite 6-month outcome (39.9% vs
      29% with no chest pain, P =.0472). For all unstable angina categories,
      atherectomy was associated with worse overall outcomes than angioplasty.
      CONCLUSIONS: Patients with unstable angina have more complications of
      percutaneous revascularization than patients without unstable angina, but event
      rates vary by anginal subgroup. The clinical presentation may help to identify
      unstable angina patients at particularly high risk for adverse outcomes.

PMID- 9924156
TI  - Frequency and efficacy of glycoprotein IIb/IIIa therapy for treatment of
      threatened or acute vessel closure in 1332 patients undergoing percutaneous
      transluminal coronary angioplasty.
AB  - BACKGROUND: Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of
      thrombocyte aggregation and thrombus formation. Several large-scale randomized
      studies for prevention of thrombotic complications have shown their potential to
      reduce these complications in patients undergoing percutaneous transluminal
      coronary angioplasty (PTCA). It was the purpose of this observational trial to
      assess the frequency and efficacy of primary GP IIb/IIIa antagonist therapy as a
      bailout procedure for the prevention of threatened or abrupt vessel closure in
      patients after conventional balloon angioplasty. METHODS AND RESULTS: From
      January 1995 to December 1996, PTCA was performed in 1332 consecutive patients
      with coronary artery disease. Overall, threatened or abrupt vessel closure was
      observed in 63 (4.7%) patients of the patient population. In these patients,
      abciximab was administered (0.25 mg/kg body weight intravenous bolus, followed by
      a 12-hour infusion at 10 mg/min). Repeat PTCA was performed shortly after the
      administration of the abciximab bolus to achieve an optimal flow at the time of
      active GP IIb/IIIa therapy. One day after intervention, early follow-up
      angiography was performed. Follow-up after 1 year included the clinical status of
      all patients and, if possible, control angiography. Overall, the preintervention
      minimum lumen diameter (MLD) measured 0.74 +/- 0.27 mm and the diameter stenosis
      was 75% +/- 24%. The postintervention MLD increased to 2.60 +/- 0.55 mm, and the
      diameter stenosis decreased to 24% +/- 22%. At 24-hour angiographic follow-up,
      the MLD decreased to 2.47 +/- 0.49 mm and the diameter stenosis increased to 28%
      +/- 24%, correspondingly. The thrombus score decreased from 2.8 +/- 1.5 before
      abciximab treatment to 0.88 +/- 0.81 after abciximab treatment, and Thrombolysis
      In Myocardial Infarction flow grade increased from 2.1 +/- 1.1 to 2.9 +/- 0.3. In
      hospital events occurred in 2 patients. Both patients had to undergo emergency
      coronary artery bypass grafting (1 of these patients died). During long-term
      follow-up, there were 10 clinical events (1 death, 3 repeat PTCA, and 6 coronary
      artery bypass graft operations for restenosis at the target lesion site). The
      cumulative event rate after 1 year (including acute and follow-up events) for
      both the total group and for the target vessel was 19%. CONCLUSIONS: The results
      of this study demonstrate that GP IIb/IIIa antagonists are able to prevent vessel
      occlusion after PTCA complicated by subsequent threatened or abrupt vessel
      closure. In these situations, GP IIb/IIIa antagonists provide effective treatment
      for the reduction of thrombus at the target lesion site, which constitutes a
      second key element for threatened or abrupt vessel occlusion.

PMID- 9924157
TI  - Video networking of cardiac catheterization laboratories.
AB  - BACKGROUND: The purpose of this study was to assess the feasibility and accuracy
      of a video telecommunication network to transmit coronary images to provide on
      line interaction between personnel in a cardiac catheterization laboratory and a
      remote core laboratory. METHODS: A telecommunication system was installed in the
      cardiac catheterization laboratory at Kaiser Hospital, Los Angeles, and the core
      laboratory at the University of California, Irvine, approximately 40 miles away.
      Cineangiograms, live fluoroscopy, intravascular ultrasound studies and images of
      the catheterization laboratory were transmitted in real time over a dedicated T1
      line at 768 kilobytes/second at 15 frames/second. These cases were performed
      during a clinical study of angiographic guidance versus intravascular ultrasound
      (IVUS) guidance of stent deployment. During the cases the core laboratory
      performed quantitative analysis of the angiograms and ultrasound images. Selected
      images were then annotated and transmitted back to the catheterization laboratory
      to facilitate discussion during the procedure. RESULTS: A successful
      communication hookup was obtained in 39 (98%) of 40 cases. Measurements of
      angiographic parameters were very close between the original cinefilm and the
      transmitted images. Quantitative analysis of the ultrasound images showed no
      significant difference in any of the diameter or cross-sectional area
      measurements between the original ultrasound tape and the transmitted images. The
      telecommunication link during the interventional procedures had a significant
      impact in 23 (58%) of 40 cases affecting the area to be treated, the size of the
      inflation balloon, recognition of stent underdeployment, or the existence of
      disease in other areas that was not noted on the original studies. CONCLUSIONS:
      Current video telecommunication systems provide high-quality images on-line with
      accurate representation of cineangiograms and intravascular ultrasound images.
      This system had a significant impact on 58% of the cases in this small clinical
      trial. Telecommunication networks between hospitals and a central core laboratory
      may facilitate physician training and improve technical skills and judgement
      during interventional procedures. This project has implications for how
      multicenter clinical trials could be operated through telecommunication networks
      to ensure conformity with the protocol.

PMID- 9924159
TI  - Economic impact on physicians and hospitals of proposed changes in Medicare
      reimbursement for coronary interventions.
AB  - BACKGROUND: The federal government is implementing changes in reimbursement for
      angioplasty and coronary stenting. These include reductions in physician
      reimbursement and a redesignation of intracoronary stents to a different
      diagnosis-related group than other methods of intracoronary intervention.
      OBJECTIVE: The aim of this study was to examine the financial impact on
      physicians and hospitals of proposed federal reimbursement policies for
      percutaneous coronary revascularization procedures. METHODS: We modeled the
      financial effects of 3 different stenting strategies: strategy I is the most
      conservative, with stents reserved for addressing lab complications; strategy II
      stents are used for suboptimal results after attempts at conventional
      percutaneous transluminal coronary angioplasty (PTCA); strategy III is the most
      aggressive, with initial stenting of all accessible lesions. We used economic
      data on PTCA and stent costs from a 1996 dataset and made assumptions about PTCA
      and stent success rates and restenosis rates based on published data. RESULTS:
      Under current reimbursement policies, physician revenues and profits are
      approximately equal under all 3 stenting strategies. After the proposed changes,
      there is a slight financial incentive for physicians to pursue the more
      aggressive strategy III, but the major financial effect is a substantial overall
      decline in revenues with any of the 3 strategies. For hospitals, the present
      situation strongly favors the more conservative strategies, but after the
      proposed changes the more aggressive stenting strategies will be more profitable,
      thus realigning physician and hospital incentives. Health care delivery
      organizations that combine physician and hospital income streams achieve the
      greatest financial stability. CONCLUSIONS: Current reimbursement policies for
      angioplasty and stenting have created misaligned incentives between physicians
      and hospitals. Proposed changes do not present physicians with large economic
      incentives to pursue aggressive versus conservative stent strategies but
      substantially address the current disparity in hospital financial incentives.

PMID- 9924158
TI  - Effectiveness of heparin in preventing thrombin generation and thrombin activity
      in patients undergoing coronary intervention.
AB  - BACKGROUND: Thrombus is important in the pathophysiology of several complications
      of angioplasty, including abrupt closure and restenosis. Levels of prothrombin
      fragment F1.2 and fibrinopeptide A reflect thrombin generation and activity. The
      effect of angioplasty on levels of these markers is unclear. METHODS: Patients
      undergoing either balloon angioplasty (n = 30) or directional atherectomy (n = 9)
      were treated with heparin to maintain an activated clotting time of >300 seconds.
      Levels of F1.2, fibrinopeptide A, and thrombin-antithrombin complex were measured
      in the coronary sinus and coronary artery before and after intervention.
      Angiograms were reviewed for lesion morphologic characteristics and dissection.
      RESULTS: There was no evidence for thrombin generation or increased thrombin
      activity after angioplasty regardless of lesion morphologic characteristics,
      dissection, type of intervention, or blood sampling site. In fact, coronary sinus
      concentrations of F1.2 decreased after intervention (median 0.31 nmol/L; 25th
      percentile 0.26 nmol/L, 75th percentile 0.37 nmol/L) before intervention to 0.23
      nmol/L (25th percentile 0.19 nmol/L, 75th percentile 0.34 nmol/L) after
      intervention (P =.002). CONCLUSIONS: Angioplasty performed in the presence of
      adequate heparin inhibited thrombin even when there was complex lesion morphology
      or dissection. These data suggest that heparin provides satisfactory thrombin
      inhibition during routine angioplasty.

PMID- 9924160
TI  - Clinical risk factors for ischemic complications after percutaneous coronary
      interventions: results from the EPIC trial. The EPIC Investigators.
AB  - BACKGROUND: Most analyses of complications after percutaneous coronary
      intervention have been limited to angiographic predictors of abrupt closure. We
      sought to determine the relation between baseline clinical and angiographic
      characteristics and clinical ischemic events and whether treatment with the
      platelet glycoprotein IIb/IIIa receptor antagonist c7E3 reduced ischemic events
      differentially in patients with distinct lesion morphologic characteristics. In
      the EPIC trial, a bolus and infusion of c7E3 decreased the 30-day incidence of
      death, myocardial infarction, and need for revascularization by 35% in 2099 high
      risk patients. METHODS: We used logistic regression modeling to determine the
      relations between these patients' baseline clinical and angiographic
      characteristics and the composite primary end point. We also constructed
      multivariable models with interaction terms to assess treatment effect on
      prespecified, core laboratory-assessed, coronary morphologic characteristics.
      RESULTS: The most important predictors of a poor outcome were low weight (chi
      square = 10.5, P =.001) and preprocedural percent stenosis (chi-square = 15.0, P
      <.001). History of hypertension, nonwhite race, and peripheral vascular disease
      were also associated with an increased risk, as were all measures of lesion
      complexity except calcification and presence of a side branch. The treatment
      benefit with abciximab was significantly greater with less complex than with more
      complex lesion morphologic characteristics. CONCLUSIONS: Future risk models
      should include these baseline characteristics to define the risk for ischemic
      complications in individual patients, and treatment with abciximab should not be
      predicated on lesion morphologic findings alone.

PMID- 9924161
TI  - Systemic and translesional activation of coagulation, fibrinolytic, and
      inhibitory systems in candidates for coronary angioplasty: basal state and effect
      of successful dilation.
AB  - OBJECTIVES: Thrombosis is a major contributor to complications associated with
      coronary interventions. It is unclear whether patients who have undergone
      angioplasty are predisposed to thrombus formation because of underlying
      perturbations in their hemostatic equilibrium. METHODS: Concentration or activity
      was measured for 14 plasma proteins involved in the coagulation, fibrinolytic,
      and inhibitory systems. Baseline systemic measurements were compared between
      patients undergoing balloon angioplasty (n = 15) and normal subjects (n = 32),
      with sampling repeated at the end of the procedure. To better assess the local
      hemostatic environment near the site of dilation, intracoronary arterial samples
      were also obtained just proximal and distal to the dilated stenosis. RESULTS:
      Multiple differences in measured coagulation proteins were found at baseline
      between the angioplasty candidates and control subjects, including higher mean
      concentration of plasma fibrinogen (P <.001) and lower high-molecular-weight
      kininogen concentration (P <.01) and factor XII activity (P <.01). Concentrations
      of the inhibitory proteins antithrombin III and protein S also differed
      significantly (P <.001 and P <.01, respectively), with a trend toward lower
      protein C concentration as well (P <.05). Finally, heightened fibrinolysis was
      suggested by a marked increase in mean plasma d-dimer concentration in the
      angioplasty candidates (293 +/- 191 ng/mL vs 116 +/- 31 ng/mL, P <.01), with a
      more modest increase in tissue plasminogen activator (P <.05) and decrease in
      alpha2-antiplasmin (P <.001). Importantly, none of the parameters obtained during
      the procedure differed significantly from samples obtained before and after
      angioplasty, and no translesional gradients were observed. CONCLUSIONS: Patients
      with active ischemic syndromes who are considered candidates for coronary
      angioplasty demonstrate significant and multiple alterations in their
      coagulation, inhibitory, and fibrinolytic systems. However, no further changes
      were observed during coronary dilation, either systemically or locally, after
      pretreatment with typical doses of heparin and aspirin.

PMID- 9924162
TI  - Direct comparison of early elevations of cardiac troponin T and I in patients
      with clinical unstable angina.
AB  - BACKGROUND: The aim of this study was to compare the prognostic efficacy of
      cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina.
      METHODS: We studied 74 patients with chest pain at rest, electrocardiographic
      evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine
      kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and
      cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All
      patients had blood drawn at baseline and 8 hours thereafter. The prospectively
      defined end point was the proportion of patients identified by each assay as
      having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same
      percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1
      or both markers. In 13 there were elevations of both. Ten patients had elevations
      of only one (5 for each marker). In 51 patients, no elevations were present.
      Death or nonfatal myocardial infarction was more frequent in patients with
      elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The
      prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the
      difference between the 2 markers when compared directly was not statistically
      significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both
      markers identify myocardial damage in equal numbers of patients with clinical
      unstable angina. Patients with elevations had a worse short-term outcome. The
      significance of the minor differences in prognostic value will require additional
      studies.

PMID- 9924163
TI  - Long-term follow-up study of coronary reconstruction with multiple stents.
AB  - BACKGROUND: Conventional balloon angioplasty of very long de novo coronary
      lesions or very long coronary dissection caused by angioplasty is associated with
      low success and high complication rates. Multiple intracoronary stents have been
      used to treat both conditions, although long-term efficacy has not been defined.
      METHODS AND RESULTS: Between June 1993 and December 1995, 47 consecutive patients
      underwent native coronary angioplasty and stenting with 4 or more stents covering
      at least 2 consecutive diseased coronary segments. Preangioplasty and
      poststenting diameter stenoses were 81% +/- 13% and 21% +/- 12%, respectively.
      Reference vessel diameters were 3.53 +/- 0.55 mm proximal to the stents and 2. 95
      +/- 0.62 mm distal to the stents. Average lesion length was 63 +/- 20 mm. The
      number of stents used was 4.5 +/- 1 per vessel (from 4 to 7). Gianturco Roubin I
      stents were used in all patients. Coronary Palmaz-Schatz stents were used as
      supplementary stents in 3 patients. Angiographic success was 100%. In-hospital
      outcomes include 1 death, 1 coronary bypass surgery, no Q-wave myocardial
      infarction, and 7 non-Q-wave myocardial infarctions. Long-term follow-up at 430
      +/- 199 days was completed in all patients. Thirty-five (76%) patients were
      asymptomatic, 8 (17%) had class 1 or 2 angina, 1 had a myocardial infarction, 13
      (28%) underwent repeat angioplasty, 2 patients had subsequent elective bypass
      surgery, and 3 died during follow-up. CONCLUSIONS: Multiple intracoronary stents
      for very long lesions or dissection can be performed with acceptable immediate
      and long-term outcomes.

PMID- 9924164
TI  - Physical examination in valvular aortic stenosis: correlation with stenosis
      severity and prediction of clinical outcome.
AB  - BACKGROUND AND METHODS: The goal of this study was to examine the ability of
      physical examination to predict valvular aortic stenosis severity and clinical
      outcome in 123 initially asymptomatic subjects (mean age 63 +/- 16 years, 70%
      men) followed up for a mean of 2.5 +/- 1.4 years. RESULTS: Doppler aortic jet
      velocity correlated with systolic murmur intensity (P =.003) and timing (P
      =.0002), a single second heart sound (P =.01), and carotid upstroke delay (P
      <.0001) and amplitude (P <.0001). However, no physical examination findings had
      both a high sensitivity and a high specificity for the diagnosis of severe
      valvular obstruction. Clinical end points were reached in 56 subjects (46%),
      including 8 deaths and 48 valve replacements for symptom onset. Univariate
      predictors of outcome included carotid upstroke delay (P =.0008) and amplitude (P
      =.0006), systolic murmur grade (P <.0001) and peak (P =.0003), and a single
      second heart sound (P =.003). On multivariate Cox regression analysis, the only
      physical examination predictor of outcome was carotid upstroke amplitude (P
      =.0001). CONCLUSIONS: Although physical examination findings correlate with
      stenosis severity, echocardiography still is needed to exclude severe obstruction
      reliably when this diagnosis is suspected.

PMID- 9924165
TI  - Underutilization of antithrombotic therapy in elderly rural patients with atrial
      fibrillation.
AB  - BACKGROUND: Antithrombotic agents are underutilized in elderly patients with
      atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri,
      rural patients were given antithrombotic therapy less often than rural patients
      for unclear reasons. METHODS AND RESULTS: The charts of 597 hospitalized Medicare
      patients discharged between October 1, 1993, and December 31, 1994, from urban
      and rural hospitals in Missouri were reviewed. In addition to antithrombotic
      therapy prescribed at the time of discharge, patient and physician information,
      relative contraindications to antithrombotic therapy, and risk factors for stroke
      were identified. Rural and urban patients were similar in terms of age, sex, and
      risk factors for stroke. At least one stroke risk factor was noted in 87% of
      rural patients and in 84% of urban patients. Urban patients were more likely to
      have a relative contraindication to antithrombotic therapy compared with rural
      patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58%
      vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly
      more often than noncardiologists (69% vs 52%, P =.003). CONCLUSIONS: Elderly
      rural patients with atrial fibrillation receive antithrombotic therapy less
      frequently than urban patients despite having a similar high-risk profile and
      fewer relative contraindications. Primary care physicians prescribe
      antithrombotic therapy less often than cardiologists, which is one of the reasons
      for this underutilization.

PMID- 9924166
TI  - SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK: an
      international randomized trial of emergency PTCA/CABG-trial design. The SHOCK
      Trial Study Group.
AB  - BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients
      hospitalized with acute myocardial infarction (MI). Nonrandomized studies suggest
      reduced mortality rate with revascularization. TRIAL DESIGN: The SHOCK trial is a
      multicenter, randomized, and unblinded study with a Registry for trial-eligible
      and ineligible nonrandomized patients. The trial is testing the hypothesis that a
      direct invasive strategy of emergency revascularization for patients with
      cardiogenic shock complicating acute MI will reduce 30-day all-cause mortality
      rate by 20 absolute percentage points compared with initial medical
      stabilization. Eligibility criteria include development of CS within 36 hours of
      an acute transmural MI as evidenced by ST elevation or new left bundle branch
      block MI; clinical criteria for CS with hemodynamic confirmation; absence of a
      mechanical, iatrogenic, or other cause of shock; and enrollment within 12 hours
      of CS diagnosis. Patients randomly assigned to emergency revascularization
      immediately undergo coronary angiography, with percutaneous transluminal coronary
      angioplasty or coronary artery bypass grafting depending on the coronary anatomy.
      Patients assigned to initial medical stabilization may undergo revascularization
      >/=54 hours after randomization. END POINTS: The primary end point is all-cause
      30-day mortality after randomization. Secondary end points include death at trial
      termination, changes in left ventricular dimensions and function measured by
      echocardiography at randomization and 2 weeks later, and changes in quality of
      life and physical functioning from 2 weeks after discharge to 6 months after MI.

PMID- 9924167
TI  - Clinical predictors of in-hospital prognosis in unstable angina: ECLA 3. The ECLA
      Collaborative Group.
AB  - OBJECTIVES: Because of recent changes in the treatment of unstable angina, we
      wanted to reassess the short-term prognostic value of clinical and
      echocardiographic variables. METHODS: This was an observational, prospective
      study that included 1038 nonselected consecutive patients admitted to coronary
      care units for unstable angina. RESULTS: Baseline characteristics were age 60.18
      +/- 16 years, history of prior myocardial infarction in 336 patients (32%), and a
      history of previous angina in 817 patients (78.7%). Angina during the 48 hours
      before admission was observed in 1004 patients (96.7%) and ST-segment changes on
      admission electrocardiogram occurred in 385 patients (37%). In-hospital treatment
      consisted of nitrates in 81.4% of patients, aspirin in 88.6%, beta-blockers in
      71%, intravenous heparin in 34.5%, subcutaneous heparin in 23%, and angioplasty
      or coronary artery bypass grafting in 25.1%. After admission, angina occurred in
      443 patients (40.8%), refractory angina in 223 patients (21.5%), and death or
      myocardial infarction in 84 patients (8.1%). At admission, the independent
      predictors of myocardial infarction or death identified by multivariate logistic
      regression analysis were ST-segment depression (odds ratio [OR] 2.13, 95%
      confidence interval [CI] 1.23 to 3.68, P =.006), prior angina (OR 2.23, 95% CI
      0.98 to 5.05, P =.05), number of episodes of angina within the previous 48 hours
      (OR 1.63, 95% CI 0.98 to 2.70, P =.05), and history of smoking (OR 0.69, 95% CI
      0.56 to 0.85, P =.004). Age greater than 65 years (OR 1.49, 95% CI1.09 to 2.03, P
      = 0.03) was significantly related to in-hospital death. The area under the
      receiver operating characteristic curve for application of this model was 0.59.
      Sensitivity was 80% with a specificity of only 33%. Refractory angina after
      admission showed a strong relation with an adverse short-term outcome.
      CONCLUSIONS: With current therapy, clinical and electrocardiographic variables
      provide useful information about the short-term outcome of unstable angina.
      However, this model has low specificity to identify high-risk patients. Future
      studies about the incremental value of the new serum markers such as troponin T
      and C-reactive protein to assist in identification of high-risk patients are
      necessary.

PMID- 9924168
TI  - Implementation of serum cardiac troponin I as marker for detection of acute
      myocardial infarction.
AB  - BACKGROUND: The goal of this prospective study was to assess whether cardiac
      troponin I (cTnI) could replace creatine kinase (CK)-MB mass as the serum
      biochemical marker for detection of acute myocardial infarction (AMI). METHODS
      AND RESULTS: Over a 3-month period, 327 nonselected, consecutive patients were
      evaluated for AMI with the use of modified World Health Organization criteria
      including serial electrocardiographs and CK-MB mass determinations at admission
      and 6, 12, and 24 hours after admission. cTnI measurements were also made at all
      time points. Sixty-two (19%) patients were diagnosed with AMI. Diagnostic
      sensitivity and specificity for peak concentrations were equivalent or better for
      cTnI (100%; 96.3%) compared with CK-MB (88. 2%; 93.2%) and total CK (73.5%;
      84.6%), respectively. cTnI demonstrated 100% negative predictive accuracy for
      ruling out AMI. Further, cTnI maintained a high diagnostic sensitivity (>94%) up
      to 96 hours after onset of chest pain compared with CK-MB and total CK (both 50%
      sensitive) in patients with AMI. However, patients with documented Q-wave
      infarctions had a significantly longer clearance compared with non-Q-wave
      infarctions (dagger(1/2) 24.2 vs 7.3 hours, respectively; P <.01). There was a
      significant (P <.02) positive correlation (r = 0.89) between increasing CK-MB
      mass and increasing cTnI for AMI specimens. CONCLUSIONS: These findings have
      strongly supported our clinical implementation of cTnI, replacing CK-MB mass as
      the preferred marker for detection of AMI.

PMID- 9924169
TI  - Lower thrombolytic use for African Americans with myocardial infarction: an
      influence of clinical presentation?
AB  - BACKGROUND: After myocardial infarction, African Americans have been reported to
      undergo fewer catheterization and revascularization procedures than whites, but
      few studies have addressed racial variations in the delivery of thrombolytic
      therapy. METHODS: We conducted a retrospective analysis of data prospectively
      collected on consecutive patients admitted with acute myocardial infarction to
      the 16-bed coronary care unit of a large, urban teaching hospital. RESULTS: Over
      a 5-year period, 1948 consecutive patients were admitted with acute myocardial
      infarction to a single coronary care unit. Thrombolysis was administered to 19%
      of 1024 African Americans and 29% of 924 whites (P <.01). The initial diagnostic
      impression on admission was "definite" infarction less often in African Americans
      (30%) than in whites (43%, P <.001), a difference that appeared to largely
      account for the difference in thrombolytic administration in a multivariable
      model. Mortality adjusted for age and concomitant illnesses was similar in
      African Americans compared with whites (relative risk 1.0, 95% confidence
      interval 0.78 to 1.51). CONCLUSIONS: Much of the racial variation in thrombolytic
      administration could be accounted for by differences in clinical presentation, an
      issue that requires further study.

PMID- 9924170
TI  - C-Reactive protein and coronary artery disease: additional evidence of the
      implication of an inflammatory process in acute coronary syndromes.
AB  - BACKGROUND: Inflammation might promote the development of atherosclerosis, and
      high levels of C-reactive protein (CRP) and fibrinogen are associated with an
      increased risk of acute coronary events. OBJECTIVE: We assessed the levels of CRP
      and other risk factors in patients with angiographically documented coronary
      artery disease compared with healthy volunteers and patients undergoing coronary
      angiography who had normal coronary angiograms. METHODS: Ultrasensitive
      immunoassay was used to measure CRP levels in 142 patients with coronary disease
      (group 1), 37 patients with normal coronary angiograms (group 2), and 37 control
      healthy subjects (group 3). RESULTS: CRP levels were higher in group 1 (7.1 +/-
      11.2 mg/L) compared with group 2 (4.8 +/- 4.0 mg/L) and group 3 (2.3 +/- 3.6
      mg/L). In group 1, CRP levels were higher for patients with previous myocardial
      infarction (8.7 +/- 9.2 mg/L) or unstable angina (11.6 +/- 18.8 mg/L). Though CRP
      levels in patients with coronary artery disease and stable symptoms were higher
      compared with healthy volunteers (5.15 +/- 7.2 mg/L vs 2.3 +/- 3.6 mg/L, P <.05),
      they were similar to those observed in the control population of patients with
      normal coronary angiograms (4.8 +/- 4.0 mg/L). Furthermore, CRP levels were
      positively correlated to plasma fibrinogen but not to Chlamydia pneumoniae or
      Helicobacter pylori serology. CONCLUSION: These results suggest that CRP has a
      strong association with acute coronary events but do not support the hypothesis
      that CRP is a potent determinant of chronic stable coronary disease.

PMID- 9924171
TI  - Hospitalization of patients with heart failure: National Hospital Discharge
      Survey, 1985 to 1995.
AB  - BACKGROUND: In the United States, heart failure has emerged as the leading first
      listed diagnosis among hospitalized older adults. METHODS: The number and
      prevalence of hospitalizations, procedure use, and discharge outcomes for men and
      women aged >/=35 years hospitalized with heart failure were estimated from
      National Hospital Discharge Survey data for the years 1985 through 1995. RESULTS:
      In 10 years, the number of hospitalizations increased from 577,000 to 871,000 for
      a first-listed diagnosis and from 1.7 to 2.6 million for any diagnosis of heart
      failure. Almost 78% of men and 85% of women hospitalized with heart failure were
      aged >/=65 years. Among persons hospitalized with any diagnosis of heart failure,
      in-hospital mortality rate decreased from 1985 to 1995 whereas prevalence of
      discharge to long-term care increased. In 1995, 67% of male patients were
      discharged home, 12% were discharged to long-term care, and 8% died during
      hospitalization; the corresponding values for female patients were 58%, 21%, and
      8%. Men had twice the prevalence of invasive cardiac procedures as did women
      during hospitalization. CONCLUSIONS: The growing burden of heart failure can be
      expected to increase during the next decade unless innovative interventions and
      primary and secondary prevention strategies are implemented.

PMID- 9924172
TI  - Association of Killip class on admission and left ventricular dilatation after
      myocardial infarction: a closer look into an old clinical classification.
AB  - BACKGROUND: Early identification of patients in whom left ventricular dilatation
      is likely to occur may have important therapeutic implications. Thus the purpose
      of this study was to evaluate the relation between Killip class on admission and
      subsequent left ventricular dilatation after acute myocardial infarction. METHODS
      AND RESULTS: We serially evaluated 129 consecutive patients by two-dimensional
      and Doppler echocardiography on days 1, 2, 3, and 7, at 3 and 6 weeks, and at 3,
      6, and 12 months after infarction. Killip class on admission >1 was found in 29
      of 129 (22.5%) patients, and they had significantly higher end-systolic and end
      diastolic volume indexes and wall motion score index from day 1 onward compared
      with patients with Killip class 1, whereas ejection fraction was lower during the
      follow-up period in these patients. Patients with Killip class >1 showed the
      progressive increase of end-diastolic (68.2 +/- 2.99 to 88.0 +/- 7.55 ml/m2, p =
      0.001) and end-systolic volume indexes (43.9 +/- 2.67 to 56.3 +/- 6. 18 ml/m2, p
      = 0.004) during the follow-up period, whereas ejection fraction and wall motion
      score index remained unchanged. In patients with Killip class 1, end-systolic
      volume index did not change (30.8 +/- 1.06 to 33.8 +/- 2.15 ml/m2, p = 0.064),
      ejection fraction increased (49.3% +/- 0.99% to 51.8% +/- 1.17%, p = 0.027), and
      wall motion score index decreased (1.50 +/- 0.03 to 1.35 +/- 0.04, p < 0. 001).
      End-systolic volume index was the major independent correlate of Killip class,
      followed by history of diabetes and peak creatine kinase level. No association
      was found between Doppler indexes of diastolic filling and Killip class on
      admission. CONCLUSIONS: Killip class >1 on admission is associated with both
      acute and long-term left ventricular dilatation. On the other hand, Killip class
      1 is associated with favorable left ventricular functional indices, and it
      appears that left ventricular function in these patients may improve over time.
      Initial end-systolic volume index but not ejection fraction is the major
      correlate of Killip class.

PMID- 9924173
TI  - Intravascular ultrasound and stent implantation: intraobserver and interobserver
      variability.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) imaging can be used to optimize
      implantation of intracoronary stents; the variability of the measurements,
      however, remains unclear. Our aim in this study was to determine the
      intraobserver and interobserver variability of IVUS measurements after stent
      implantation. METHODS: Ninety-four patients underwent implantation of 100 Palmaz
      Schatz stents in 98 lesions (79 de novo and 19 restenotic). IVUS measurements
      (3.5F, 30 MHz) of proximal and distal reference sections and of the smallest
      stent lumen were performed by 2 investigators. RESULTS: Intraobserver and
      interobserver correlations, respectively, were r = 0.96 and 0.93 for the proximal
      reference, r = 0.94 and 0.92 for the distal reference, and r = 0.97 and 0.97 for
      minimal stent lumen. Stent expansion (minimal lumen in the stent/mean reference
      area) showed a variability of r = 0.80 and 0.70. Taking a cutoff point of 90% for
      adequacy of stent expansion, observers agreed in only 77% whether the stent was
      adequately or inadequately expanded. CONCLUSIONS: IVUS enables reproducible lumen
      measurements in stents and reference sections. The degree of stent expansion,
      however, underlies a high measurement variability that can lead to different
      therapeutic strategies.

PMID- 9924174
TI  - Peroxisome proliferator-activated receptor alpha: role in rodent liver cancer and
      species differences.
AB  - Peroxisome proliferators (PPs) are chemicals of industrial and pharmaceutical
      importance that elicit liver carcinogenesis by a non-genotoxic mechanism. One of
      the intriguing properties of PPs is that the pleiotropic effects of these
      compounds (including increased DNA synthesis and peroxisome proliferation) are
      seen in rats and mice only, but not humans. It is important to determine the
      risks to humans of environmental and therapeutic exposure to these compounds by
      understanding the mechanisms of non-genotoxic hepatocarcinogenesis in rodents. To
      understand this apparent lack of human susceptibility, attention has focused on
      the peroxisome proliferator-activated receptor alpha (PPARalpha), which appears
      to mediate the effects of PPs in rodents. It is also known to mediate the
      hypolipidaemic effects that fibrate drugs exert on humans with elevated plasma
      cholesterol and triglyceride levels. Human PPARalphas share many functional
      characteristics with the rodent receptors, in that they can be transcriptionally
      activated by PPs and regulate specific gene expression. However, one key
      difference is that PPARalpha is less abundant in human than in rodent liver,
      which has led to the suggestion that species differences result from quantitative
      differences in gene expression. In this review we describe the effects of PPs and
      what is known of the molecular mechanisms of action and species differences with
      respect to rodents and man. Attention will be given to differences in the amounts
      of PPARalpha between species as well as the 'qualitative' aspects of PPARalpha
      mediated gene regulation which might also explain the activation of some genes
      and not of others in human liver by PPs.

PMID- 9924175
TI  - Gene therapy strategies for the treatment of pituitary tumours.

PMID- 9924176
TI  - Tyrosine kinases play a permissive role in glucose-induced insulin secretion from
      adult rat islets.
AB  - The role(s) played by protein tyrosine kinases (PTKs) in the regulation of
      insulin secretion from pancreatic beta cells is not clear. We have examined the
      effects of glucose, the major physiological insulin secretagogue, on the tyrosine
      phosphorylation state of islet proteins, and assessed beta cell insulin secretory
      responses in the presence of PTK inhibitors. Under basal conditions islets
      contained many proteins phosphorylated on tyrosine residues, and glucose (20 mM;
      5-15 min) was without demonstrable effect on the pattern of tyrosine
      phosphorylation, in either the absence or presence of the protein tyrosine
      phosphatase (PTP) inhibitor, sodium pervanadate (PV). PV alone (100 microM)
      increased tyrosine phosphorylation of several islet proteins. The PTK inhibitors
      genistein (GS) and tyrphostin A47 (TA47) inhibited islet tyrosine kinase
      activities and glucose-, 4alpha ketoisocaproic acid (KIC)- and sulphonylurea
      stimulated insulin release, without affecting glucose metabolism. GS and TA47
      also inhibited protein serine/threonine kinase activities to a limited extent,
      but had no effect on Ca2+, cyclic AMP- or phorbol myristate acetate (PMA)-induced
      insulin secretion from electrically permeabilised islets. These results suggest
      that PTK inhibitors exert their inhibitory effects on insulin secretion proximal
      to Ca2+ entry and it is proposed that they act at the site of the voltage
      dependent Ca2+ channel which regulates Ca2+ influx into beta cells following
      nutrient- and sulphonylurea-induced depolarisation.

PMID- 9924177
TI  - Cloning and characterisation of the gene encoding mole rat (Spalax ehrenbergi)
      growth hormone.
AB  - In mammals the structure of pituitary GH is generally strongly conserved,
      reflecting a slow basal rate of molecular evolution. However, on a few occasions
      the rate has increased - markedly during the evolution of primates and
      artiodactyls, and to a small extent during the evolution of rodents and rabbit -
      giving rise to marked differences between GH sequences of these species. In order
      to extend knowledge of rodent GHs we have cloned and characterised part of the GH
      gene of the Eurasian mole rat (Spalax ehrenbergi) using genomic DNA and a PCR
      technique. The sequence of all of the coding region and 5' untranslated region
      (UTR), most of the 3' UTR and part of the promoter region is described. The
      overall organisation of the mole rat GH gene is similar to that of GH genes from
      other mammals. The proximal Pit-1 sequence in the gene promoter differs somewhat
      from that of rat or mouse. The deduced sequence for the mature GH from mole rat
      differs from that of pig GH (thought to be identical to the ancestral placental
      mammal GH sequence) at 7 residues and from rat, mouse and hamster GHs at 9 to 12
      residues. Only one or two of these substitutions involve residues close to the
      receptor-binding sites of the hormone.

PMID- 9924178
TI  - Differential immunolocalization of estrogen receptor alpha and beta in rat ovary
      and uterus.
AB  - In order to investigate the localization of estrogen receptor (ER) alpha and
      ERbeta in the reproductive organs in the rat, polyclonal antibodies were raised
      to each specific amino acid sequence. The Western blot with anti-ERalpha antibody
      showed a 66 kDa band in rat ovary and uterus, while that with anti-ERbeta
      antibody detected a 55 kDa band in rat ovary, uterus and prostate. The ligand
      independent nuclear localization of the two receptors was verified by
      immunocytochemistry. By immunohistochemistry, the nuclei of glandular and luminal
      epithelial cells in the uterus were stained with anti-ERalpha antibody, whereas
      only the nuclei of glandular epithelium cells were stained with anti-ERbeta
      antibody. In rat ovary, positive signals were shown with anti-ERbeta antibody in
      the nuclei of granulosacells. No specific immunostaining was observed with anti
      ERalpha antibody. Although ERbeta was immunostained at the proestrous, metestrous
      and diestrous stages, the immunoreactivity of ERbeta was hardly detected at the
      estrous stage in rat ovary. Thus, we show differential expression of ERalpha and
      ERbeta in rat uterus and ovary at the protein level, which may provide a clue for
      understanding the roles of the two receptors in reproductive organs.

PMID- 9924179
TI  - GnRH agonist treatment decreases progesterone synthesis, luteal peripheral
      benzodiazepine receptor mRNA, ligand binding and steroidogenic acute regulatory
      protein expression during pregnancy.
AB  - We have demonstrated that continuous administration of a gonadotropin-releasing
      hormone agonist (GnRH-Ag) suppresses luteal steroidogenesis in the pregnant rat.
      We further demonstrated that the peripheral-type benzodiazepine receptor (PBR)
      and the steroidogenic acute regulatory protein (StAR) play key roles in
      cholesterol transport leading to steroidogenesis. The purpose of this study was
      to understand the cellular and molecular mechanisms involved in the suppression
      of luteal steroidogenesis leading to a fall in serum progesterone levels in GnRH
      Ag-treated rats during early pregnancy. Pregnant rats were treated individually
      starting on day 8 of pregnancy with 5 microgram/day GnRH-Ag using an osmotic
      minipump. Sham-operated control rats received no treatment. At 0, 4, 8 and 24 h
      after initiation of the treatment, rats were killed and corpora lutea (CL) were
      removed for PBR mRNA, protein and radioligand binding analyses, immunoblot 1-D
      gel analysis of StAR, P450 scc and 3beta-hydroxysteroid dehydrogenase as well as
      2-D gel analysis of StAR. The treatment decreased the luteal PBR mRNA expression
      at all time periods starting at 4 h compared with that in corresponding sham
      controls. GnRH-Ag also reduced, in the CL, the PBR protein/ligand binding, the
      StAR protein and P450 scc protein and its activity as early as 8 h after the
      treatment and they remained low compared with those in corresponding sham
      controls. The data from 2-D gel studies suggest that the majority of the decrease
      in StAR protein appears to be in the phosphorylated forms of StAR. Thus, we have
      demonstrated, for the first time, the presence of PBR and StAR in the pregnant
      rat CL and that the coordinated suppression of these proteins involved in the
      mitochondrial cholesterol transport along with P450 scc by GnRH-Ag leads to
      reduced ovarian steroidogenesis.

PMID- 9924180
TI  - The decrease in the short variant of gsalpha protein is associated with an
      increase in [3H]CGP12177 binding, [3H]ouabain binding and Na, K-ATPase activity
      in brown adipose tissue plasma membranes of cold-acclimated hamsters.
AB  - Sucrose density gradient purified plasma membranes isolated from brown adipose
      tissue of cold-acclimated hamsters (4-10 weeks at 0-4 degreesC) were analysed for
      the content of the short (GsalphaS) and long (GsalphaL) variants of Gsalpha
      protein (the alpha subunit of the stimulatory G protein) and compared with the
      membranes isolated from control animals. The relative ratio between the two
      variants (GsalphaS/GsalphaL) decreased from 0.48 to 0.24 (P<0.01). This result,
      obtained by electrophoretic resolution of membrane proteins by standard SDS-PAGE
      and an immunoblot analysis with an antiserum oriented against an internal
      sequence of Gsalpha, was verified by resolution on urea-containing gels and an
      antiserum oriented against the C-terminus decapeptide of Gsalpha. Under these
      conditions, the GsalphaS/GsalphaL ratio was decreased from 0.41 to 0.31 (P<0.05).
      The total amount of both isoforms (GsalphaS plus GsalphaL) decreased to 83%
      (P<0.05) or 68% (P<0.01) by standard or urea SDS-PAGE respectively. These data
      demonstrate that cold-acclimation of hamster brown adipose tissue is associated
      with preferential decrease in the plasma membrane density of the short variant of
      the Gsalpha protein.%This decrease was paralleled by an increase in the other
      plasma membrane constituents, [3H]CGP12177 binding sites, [3H]ouabain binding
      sites and Na,K-ATPase activity to 147%, 212% and 191% respectively.

PMID- 9924181
TI  - Poly(ADP-ribose)polymerase activation determines strain sensitivity to
      streptozotocin-induced beta cell death in inbred mice.
AB  - Streptozotocin (STZ) is believed to induce pancreatic beta cell death in mice by
      depleting the cell of NAD+NADH. The drug is known to cause a greater depletion of
      beta cell NAD+NADH in C57bl/6J mice than in Balb/c mice. To investigate the basis
      for this strain difference, we compared the effects of streptozotocin on poly(ADP
      ribose)polymerase (PARP) activation - the major site of NAD consumption, and on
      mitochondrial activity - the major site of NAD production.%A significant strain
      difference was demonstrated in STZ-induced PARP activation (fmol NAD
      incorporated/min/microgram DNA+/-s.e.m.: Balb/c control 2.28+/-0.14, Balb STZ
      3.11+/-0.25; C57bl/6J control 2.57+/-0.29, C57bl/6J STZ 4.17+/-0.24). In
      comparison, no strain difference could be demonstrated in hydrogen-peroxide
      induced PARP activation. No strain differences could be detected in the activity
      of STZ-treated islet mitochondria as measured by determining ATP production
      (pmol/microgram protein/h+/-s. e.m.: Balb/c control 0.20+/-0.02, Balb/c STZ
      0.15+/-0.02; C57bl/6J control 0.23+/- 0.03, C57bl/6J STZ 0.15+/-0.02) or by 3-[4,
      5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction
      (change in optical density/mg protein+/-s.e.m.: Balb/c control 10.19+/-0.62,
      Balb/c STZ 6.01+/-1.17; C57bl/6J control 6. 15+/-0.98, C57bl/6J STZ 5.81+/
      0.96).% The strain difference in STZ-induced NAD depletion appears to be due to a
      difference in NAD consumption and not a difference in a mitochondrial process
      involved in replacing decreasing NAD concentrations. It is unlikely that a strain
      difference in the enzymic activity of PARP is responsible for strain differences
      in the effects of STZ, as no strain differences in hydrogen-peroxide-induced PARP
      activation could be detected. Thus the greater PARP activation, NAD depletion and
      beta cell death observed in C57bl/6J islets may be due to greater levels of DNA
      damage or differences in the DNA excision repair processes.

PMID- 9924182
TI  - Insulin-glucocorticoid interactions in the regulation of acetyl-CoA carboxylase
      alpha transcript diversity in ovine adipose tissue.
AB  - Transcription of the acetyl-CoA carboxylase (ACC)-alpha gene is initiated from
      two promoters, promoter I (PI) and promoter II (PII) such that transcripts
      demonstrate heterogeneity in their 5' untranslated regions (UTR). Exons 1 and 2
      (E1 and E2) are the primary exons in transcripts initiated from PI and PII
      respectively; E5 is the first coding exon present in all transcripts. In addition
      alternative exon splicing results in transcripts that either include or exclude a
      47 nucleotide sequence corresponding to E4, such that E[1/4/5] and E[1/5] type
      transcripts result from PI activity, whereas transcripts containing E[2/4/5] or
      E[2/5] in the 5'UTR result from PII. In subcutaneous adipose tissue from non
      pregnant non-lactating sheep approximately 60% of ACC-alpha transcripts are
      derived from PI, of which 85% are the E[1/5] type. Lactation resulted in an 88%
      reduction in total PI transcripts, of which the E[1/5] type was reduced 90% and
      the E[1/4/5] type 80%. By contrast lactation reduced the total levels of PII
      transcripts by only 50%. Culture of explants from the subcutaneous depot of
      lactating sheep with insulin plus dexamethasone for 72 h resulted in an 8-fold
      increase in both E[1/4/5] and E[1/5] types when compared with explants prior to
      culture. PII transcripts, by contrast, were increased 2-fold by culture in
      insulin plus dexamethasone and this was entirely attributed to an increase in the
      expression of the E[2/4/5] type. Dexamethasone acts to potentiate the action of
      insulin on PI and PII transcript abundance and this effect is greatest for PI
      transcripts. This study has demonstrated that repression of the ACC-alpha gene in
      adipose tissue during lactation is largely achieved through attenuation of PI
      transcript abundance and may be related, in part, to a change in the sensitivity
      of the apparatus that regulates PI transcript steady-state levels to insulin.

PMID- 9924183
TI  - Glucocorticoids increase retinoid-X receptor alpha (RXRalpha) expression and
      enhance thyroid hormone action in primary cultured rat hepatocytes.
AB  - We have previously demonstrated that dexamethasone (DEX) enhances the T3
      dependent increase in type I 5'-deiodinase (5'DI) mRNA in primary cultured rat
      hepatocytes grown as spheroids. Here we report that DEX-enhanced T3
      responsiveness also occurs in two other T3-regulated hepatic genes, Spot 14 and
      malic enzyme. This enhancement was inhibited by pretreatment with cycloheximide
      and the stability of 5'DI and Spot 14 mRNAs was not affected by DEX. We thus
      hypothesized that a factor(s) that augments T3-responsiveness is induced by DEX.
      Among the possible candidates examined, retinoid-X receptor alpha (RXRalpha),
      which is a main heterodimer partner with T3 receptor, appeared to be involved.
      Whereas DEX increased the amount of RXRalpha mRNA, it did not affect the
      expression of other possible factors such as steroid receptor coactivator-1 and
      the binding protein of cAMP response element-binding protein. Northern and
      Western blot analysis, and electrophoretic mobility shift assay revealed that DEX
      increased RXRalpha expression at both the mRNA and protein levels. Maximal
      increase in RXRalpha protein was achieved with the addition of physiological
      concentrations of DEX (10(-8) M). To test whether the DEX-induced increase in
      RXRalpha affects ligand-dependent transcriptional activation through other
      receptors that form heterodimer with RXR, we examined its effect on the retinoic
      acid (RA)/RA receptor (RAR) system. Indeed, DEX also enhanced the RA-dependent
      increase in RARbeta mRNA in a cycloheximide-sensitive manner. Increase in the
      level of RXRalpha in hepatocytes by infection with the RXRalpha-expressing
      adenovirus resulted in enhancement of the T3-dependent increase in 5'DI mRNA.
      These results strongly suggest that the DEX-induced augmentation of T3
      responsiveness in cultured hepatocytes is mediated, in part, by the increased
      expression of RXRalpha.

PMID- 9924184
TI  - Cyclin D3 in the mouse uterus is associated with the decidualization process
      during early pregnancy.
AB  - In the mouse, the attachment reaction between the blastocyst trophectoderm and
      the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of
      pregnancy and is rapidly followed by transformation of stromal cells into
      decidual cells (decidual cell reaction). This process can also be induced
      experimentally (deciduoma) by intraluminal oil infusion in the uterus on day 4 of
      pseudopregnancy. The decidual cell reaction is associated with up- and down
      regulation of many genes in a cell-specific manner. Using mRNA differential
      display, we identified cyclin D3 as one of the genes that is upregulated in the
      uterus at the sites of blastocyst apposition during the attachment reaction. The
      levels of expression were low in the morning of days 1-4 as determined by
      Northern hybridization. In situ hybridization analysis showed that on days 1 and
      2, signals were primarily localized in uterine epithelial cells, while signals
      were detected in both the stromal and epithelial cells on days 3 and 4. In
      contrast, with the initiation and progression of decidualization on days 5, 6 and
      7, the levels of cyclin D3 mRNA were remarkably upregulated in stromal cells both
      at the mesometrial and the antimesometrial poles. However, on day 8, signals were
      primarily localized in stromal cells at the mesometrial decidual bed. Implanting
      blastocysts on these days also expressed cyclin D3 mRNA. In the progesterone
      treated delayed implanting mice, the uterine levels of cyclin D3 mRNA were modest
      at the sites of blastocyst apposition, but were upregulated with the onset of
      implantation by estradiol-17beta. However, the decidual expression of cyclin D3
      mRNA was not dependent on the presence of blastocysts, since increased expression
      also occurred in experimentally induced deciduoma in the absence of blastocysts.
      The importance of cyclin D3 in decidualization was further examined in Hoxa-10
      deficient mice which show defective decidualization. The expression of cyclin D3
      mRNA in Hoxa-10(-/-) uteri on day 5 was severely compromised after application of
      a deciduogenic stimulus on day 4 of pseudopregnancy. Collectively, the results
      suggest that cyclin D3 could be important for the process of decidualization.

PMID- 9924185
TI  - Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary
      adrenal axis.

PMID- 9924186
TI  - Review: The role of leukaemia inhibitory factor in the establishment of
      pregnancy.
AB  - Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine required for
      blastocyst implantation in mice. Uterine expression of LIF and that of its
      receptors has been demonstrated in a number of mammalian species indicating that
      LIF may have widespread importance in the establishment of pregnancy. The
      variations in the reaction of the uterus in preparation for and during
      implantation are considerable between species and understanding the differences
      and similarities assists in the interpretation of how this cytokine functions.
      Recent studies suggest that reduced endometrial LIF contributes to human
      infertility. Studies also demonstrate a potential role in placentation and fetal
      development. Thus, LIF has become an important cytokine warranting further
      investigation in the human. It is anticipated that when the mechanisms underlying
      normal embryonic and endometrial development are elucidated, fertility and
      infertility will be more precisely understood and hence able to be effectively
      controlled.

PMID- 9924187
TI  - Amino acid transformation of oscillatory Ca2+ signals in mouse pancreatic beta
      cells.
AB  - Glucose-induced increase of cytoplasmic Ca2+ in pancreatic beta-cells is usually
      manifested as slow oscillations from the basal level. The significance of this
      rhythmicity for maintaining normal beta-cell function with periodic variations of
      circulating insulin made it of interest to investigate how the oscillatory Ca2+
      signal was affected by various amino acids. Individual mouse beta-cells were very
      sensitive to alanine, glycine and arginine, sometimes responding with a
      transformation of the oscillations into sustained elevation of cytoplasmic Ca2+
      at amino acid concentrations as low as 0.1 mM. Stimulation of the entry of Ca2+,
      obtained either by raising the extracellular concentration or by prolonging the
      open state of the voltage-dependent Ca2+ channels with BAY K 8644, resulted in
      reappearance of the rhythmic activity in the presence of the amino acids.
      Oscillatory Ca2+ signals in intact islets were more resistant to transformation
      by amino acids than those of individual beta-cells. It is therefore suggested
      that signals from the adjacent cells make it possible for beta-cells situated in
      islets to overcome a suppression of the oscillatory activity otherwise seen in
      the presence of alanine, glycine or arginine.

PMID- 9924188
TI  - The antiprogestin RU486 dissociates LH and FSH secretion in male rats: evidence
      for direct action at the pituitary level.
AB  - Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult
      male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing
      FSH and decreasing LH secretion. In subsequent experiments we evaluated the
      involvement of testicular or adrenal secretory products, as well as hypothalamic
      LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of
      gonadotrophins. The first day of RU486 injection was designated day 1, subsequent
      days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or
      RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen
      flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii)
      bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle
      or were sham operated. To ascertain whether the secretion of LHRH is involved in
      the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion
      into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486
      treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100
      ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000
      h on days 2 and 4. Controls were given saline. All animals were decapitated at
      1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and
      testosterone assays.%While ADX had no effect on FSH and LH secretion in either
      oil- or RU486-treated rats, the removal of androgen negative feedback with
      flutamide treatment or by ORCH substantially increased serum levels of FSH and LH
      in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No
      differences in pituitary stalk plasma LHRH concentrations were found between oil-
      and RU486-treated rats. Injection of LHRH increased serum FSH and LH
      concentrations in oil-treated rats but only, and to a lesser extent, LH
      concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum
      concentrations of FSH and LH in both oil- and RU486-treated rats. These results
      suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level,
      and that FSH secretion increased in response to a reduction in the negative
      feedback of androgen.

PMID- 9924189
TI  - Parotid gland tissue is able partially to assume pituitary functions under the
      influence of hypothalamic factors: in vivo and in vitro studies.
AB  - To test whether salivary tissue can secrete pituitary hormones, female Sprague
      Dawley rats were hypophysectomized (hypox) and the following were transplanted to
      the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30),
      muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with
      dentist's cement. In addition a group of rats (group 1, n=22) remained intact as
      controls. All groups were followed for 8 months. Daily vaginal smears showed
      normal cyclicity in controls and constant dioestrus in all hypox groups. Blood
      samples, taken once every 30 days before and after LHRH stimulation, showed
      significantly lower (P<0.001) plasma LH values in all hypox groups compared with
      controls. In group 3, a gradual and significant increase (P<0.05) was observed in
      the LH response to LHRH in parallel with a partial recovery of oestrous smears.
      No LH modification was observed in the other hypox groups. Plasma prolactin (PRL)
      levels were also very low in all hypox groups and were unaltered throughout the
      study. At the end of the experiments, half the animals were killed by
      decapitation and the hypothalamic-pituitary areas carefully dissected,
      homogenized and analysed for LH and PRL content. The remaining animals were
      perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues.
      Hypothalamic and transplant areas were carefully dissected, frozen, cut and
      submitted to immunochemical procedures. LH content in the graft of group 3
      animals was markedly (P<0.001) lower than in the control pituitary, but
      significantly higher (P<0.05) than in the other hypox groups. Immunochemistry
      showed LH and PRL positive cells in the graft of group 3 animals, whereas neither
      positive cells, nor LH content were observed in the parotid gland in situ.
      Experiments were completed with in vitro cultures of parotid glands in the
      presence or absence (controls) of synthetic hypothalamic hormones or rat
      hypothalamic extracts. After 1.5 weeks of culture, a significantly higher LH
      concentration (P<0.05) was observed in the wells treated with synthetic
      hypothalamic hormones (216+/-46 pg/ml vs 41+/-6 pg/ml in controls). When
      hypothalamic extracts were used, the LH levels increased more markedly (1834+/
      190 pg/ml vs 36+/-6 pg/ml in controls) and those values were maintained during 3
      weeks of culture. Immunostaining of these cultures showed a positive LH reaction
      in the epithelial cells found in the hypothalamic extract-treated wells. Both in
      vivo and in vitro studies confirm the transdifferentiation of parotid gland
      tissue to pituitary hormone-producing cells under hypothalamic influence.

PMID- 9924190
TI  - Salivary gland is capable of GH synthesis under GHRH stimulation.
AB  - Twelve female rats weighing approximately 150 g received in the submaxillary
      gland a pellet capable of releasing 3.5 microg GHRH/h for 60 days. Another eight
      sex- and weight-matched animals received placebo pellets in the same place. After
      two months the animals were killed, heart blood was collected and pituitary and
      submaxillary glands were carefully dissected. Pituitary GH content in both
      placebo- and GHRH-treated animals showed similar values, but plasma GH and IGF-I
      levels were significantly lower in the animals carrying GHRH pellets (P<0.03);
      these animals also had a significantly higher GH content in the submaxillary
      gland (19.2+/-8 ng/mg protein) compared with the placebo-treated group (1.1+/-0.3
      ng/mg protein). GH mRNA was present only in the submaxillary gland of GHRH
      treated rats as determined by PCR-Southern blot and by in situ hybridization
      methods. It is concluded that high local GHRH levels are capable of inducing
      transdifferentiation in submaxillary gland cells to synthesize GH.

PMID- 9924191
TI  - Vitamin D analogue EB1089-induced prostate regression is associated with
      increased gene expression of insulin-like growth factor binding proteins.
AB  - Vitamin D analogues have an antiproliferative effect on prostate cancer cells in
      vitro and thus have been proposed as candidates for chemoprevention of prostate
      cancer. Insulin-like growth factor (IGF)-I has been shown to protect cells from
      apoptosis and plays an essential role in normal prostate physiology. We have
      studied the effects of the 1,25-dihydroxyvitamin D3 analogue EB1089 on the IGF
      system in the prostate in vivo. Treatment of rats with EB1089 for 14 days caused
      a 25% decrease in ventral prostate weight. Apoptosis was detected in prostate
      sections of EB1089-treated rats by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling(TUNEL) assay and histologic examination of
      hematoxylin/eosin stained tissue sections indicated that secretory epithelial
      cells were flattened, a characteristic of cells undergoing pressure-induced
      atrophy. Ventral prostate regression was associated with 15- to 25-fold increases
      in gene expression of IGF-binding proteins (IGFBPs)-2,-3,-4 and -5. We also
      observed a 40-fold increase in prostatic IGF-I mRNA levels in response to EB1089.
      Although we have previously shown that castration of rats leads to upregulation
      of IGFBPs in the ventral prostate, EB1089 treatment had no effect on serum levels
      of dihydrotestosterone or free testosterone. These results suggest that prostate
      regression induced by EB1089 may be related to alterations in availability of IGF
      I as a result of increased production of IGFBPs.

PMID- 9924192
TI  - Influence of rat placental lactogen-I on the development of whole rat embryos in
      culture.
AB  - Rat placental lactogen-I (rPL-I), the first prolactin-like hormone expressed in
      the placenta during pregnancy in the rat, is known to influence maternal
      functions. In the present study, we have investigated the effects of rPL-I on the
      growth and development of cultured whole rat embryos. Rat embryos, with or
      without ectoplacental cone (EPC) attached, were explanted at day 9 of gestation.
      After 48 h of culture, the embryos, enclosed by the yolk sacs, were assessed by
      the presence of visible heart contractions ('heart beats'), crown-rump length
      (CRL) and yolk sac diameter (YSD). When intact embryos with EPC were cultured,
      the concentrations of rPL-I and rPL-II (products of EPC) in the medium were 850+/
      841 and 92+/-181 ng/ml respectively (means+/-s.e.m.). In embryo cultures with the
      EPC removed, rPL-I levels decreased to</=10 ng/ml, and only 70% of the embryos
      were viable, with visible heart beats. In the viable embryos, both CRL and
      embryonic DNA synthesis were reduced compared with controls, and the addition of
      rPL-I (1 microg/ml) did not prevent this reduction. YSD and yolk sac DNA
      synthesis were also reduced compared with control embryos, and the addition of
      rPL-I significantly prevented this decrease by 45%. In embryos cultured without
      EPC in the presence of neutralizing rabbit anti-rat prolactin serum (anti-rPRL),
      embryonic and yolk sac DNA synthesis were reduced by 35% compared with embryos
      exposed to normal rabbit serum. Addition of rPL-I significantly increased
      (P<0.05) embryonic and yolk sac growth. Thus the effects of rPL-I on embryo
      growth could only be seen in the absence of prolactin. The addition of human
      prolactin in the presence of anti-rPRL also resulted in significant increases
      (P<0.05) in embryonic DNA synthesis and CRL. These results suggest that rPL-I may
      substitute for prolactin to influence the growth of the rat embryo.

PMID- 9924193
TI  - Isolation of radiochemically pure 125I-labeled human thyrotropin receptor and its
      use for the detection of pathological autoantibodies in sera from Graves'
      patients.
AB  - We report a method for the purification and radioactive labeling of human TSH
      receptor (TSHR). The method is based on the construction of a fusion TSHR (TSHR
      Xa-BIO) which consists of the N-terminal 725 amino acids of human TSHR linked to
      the 4-amino acid Xa protease cleavage site and the 87-amino acid C-terminal
      domain of the biotin carboxyl carrier protein subunit of Escherichia coli acetyl
      CoA carboxylase (the C-terminal domain directs the efficient posttranslational
      biotinylation of the protein). TSHR-Xa-BIO was produced in HeLa cells using
      recombinant vaccinia virus. The expressed protein was fully functional and was
      biotinylated with an efficiency of about 90%. Streptavidin-agarose-immobilized
      TSHR-Xa-BIO was labeled with 125I using the chloramine T oxidation procedure and
      specifically eluted from the solid phase after cleavage with protease Xa.
      Isolated native radiochemically pure 125I-labeled TSHR specifically interacted
      with pathological autoantibodies in the sera of patients with Graves' disease,
      and thus could be useful for the detection of these autoantibodies by
      immunoprecipitation analysis.

PMID- 9924194
TI  - GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle
      tissues of hypophysectomised rats.
AB  - Changes in GH secretion are associated with changes in serum lipoproteins,
      utilisation of fuels and body composition. Since lipoprotein lipase (LPL) is a
      key enzyme in the regulation of lipid and lipoprotein metabolism, changes in LPL
      activity may contribute to these effects of GH. The present study was undertaken
      to investigate the role of GH and the GH-dependent growth factor, IGF-I, in the
      regulation of LPL in heart, skeletal muscle and adipose tissue. Female rats were
      hypophysectomised at 50 days of age. One week later, hormonal therapy was
      commenced. All hypophysectomised rats received l-thyroxine and cortisol. Adipose
      tissue, the heart, soleus and gastrocnemius muscles were excised after 1 week of
      hormonal therapy. The effect of insulin injections on adipose tissue and heart
      LPL activity was also studied. In separate experiments, LPL activity in post
      heparin plasma was measured. Hypophysectomy had no effect on adipose tissue LPL
      activity, whereas activity was reduced in heart, soleus and gastrocnemius muscle
      tissues. GH treatment had no significant effect on LPL activity in adipose tissue
      or soleus muscle, but increased the LPL activity in heart and gastrocnemius
      muscle. GH treatment increased post-heparin plasma LPL activity. Recombinant
      human IGF-I treatment (1.25 mg/kg per day) markedly reduced LPL activity in
      adipose tissue, but had no effect in muscle tissues. The effect of IGF-I
      treatment on adipose tissue LPL was not reflected by a decrease in post-heparin
      plasma LPL activity. Daily injections of insulin for 7 days increased LPL
      activity in adipose tissue but had no effect on heart LPL activity. In adipose
      tissue, LPL mRNA levels tended to decrease as a result of IGF-I treatment. In the
      muscle tissues, no significant effects of hypophysectomy, GH or IGF-I treatment
      on LPL mRNA levels were observed.%It is concluded that GH increases heart and
      skeletal muscle tissue LPL activity, which probably contributes to an increased
      post-heparin plasma LPL activity. The effect of GH on muscle LPL activity is
      probably not mediated by IGF-I or insulin. Insulin and IGF-I have opposite
      effects on LPL activity in adipose tissue.

PMID- 9924195
TI  - Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell
      cycling in G1 in human prostate epithelium.
AB  - Transforming growth factor-beta1 (TGFbeta1) is inhibitory to most epithelia, but
      its role in the control of proliferation of prostatic epithelium is unclear. In
      some cells, TGFbeta1 inhibition is achieved by up-regulation of cyclin-dependent
      kinase (cdk) inhibitors including p15, p21 and p27. Our aims were to determine
      whether the effects of TGFbeta1 on human prostatic epithelial cell cycle kinetics
      were mediated by alterations in the levels of the cdk inhibitors p15, p16, p21
      and p27 and hypo-phosphorylated retinoblastoma protein (Rb). Human prostatic
      epithelial cells in primary culture were grown in the presence of TGFbeta1 (0-10
      ng/ml) for up to 4 days and proliferation assessed using a [3H]thymidine uptake
      assay. Levels of p15, p16, p21 and p27 were measured at both mRNA and protein
      level by means of a reverse transcriptase PCR-based assay and Western analysis.
      Rb and cdk2 levels were measured. Exogenous TGFbeta1 (0-5 ng/ml) inhibited
      proliferation. This was associated with blocking of the cell cycle at G1, and up
      to 4-fold increases in p15, p21 and p27 mRNA levels, but no change was observed
      in p16 mRNA levels; these changes were not blocked by cycloheximide. Increased
      levels of p15, p21 and p27 protein were also accompanied by increased levels of
      hypo-phosphorylated Rb and decreased cdk2 kinase activity. TGFbeta1 has mainly
      inhibitory effects on benign human prostatic epithelium, which are caused by up
      regulation of cdk inhibitors, hypo-phosphorylation of Rb and delaying of the cell
      cycle in G1.

PMID- 9924196
TI  - A novel mutation in the human thyroid peroxidase gene resulting in a total iodide
      organification defect.
AB  - In this study we describe a novel mutation of the thyroid peroxidase (TPO) gene
      that resulted in a total iodide organification defect. TPO activity and thyroxine
      formation in thyroglobulin in the thyroid gland of the patient were below the
      limits of detection. However, TPO mRNA was detectable at a similar size and
      concentration as compared with normal thyroid tissues when measured by Northern
      blot analysis. Sequence analysis of the TPO gene showed the presence of two
      mutations, a missense mutation in exon 7 and C insertion in exon 14. These
      mutations were heterozygous and located in different alleles. The latter mutation
      has already been reported as one of the mutations of the TPO gene resulting in
      total iodide organification defect. The former mutation was further analysed by
      mRNA transfection studies in which mutated mRNA was transfected to CHO-K1 cells
      by electroporation. The results of transfection studies showed that the cells
      transfected with mutated mRNA expressed similar size TPO molecules to those of
      cells transfected with wild-type mRNA but that they lacked TPO activity. The two
      mutations of the TPO gene resulting in the total iodide organification defect in
      the patient cosegregated from her parents.

PMID- 9924197
TI  - Nitric oxide synthase acutely regulates progesterone production by in vitro
      cultured rabbit corpora lutea.
AB  - We examined the presence and the regulation of nitric oxide (NO) synthase (NOS)
      using in vitro cultured corpora lutea (CL) obtained from rabbits at days 4 and 9
      of pseudopregnancy. The role of NO and NOS on steroidogenesis was also
      investigated using the same CL preparations after short-term incubations (30 min
      and 2 h) with the NO donor, sodium nitroprusside (NP), the NOS inhibitor, Nomega
      nitro-l-arginine methyl ester (l-NAME) and prostaglandin (PG) F-2alpha. The basal
      NOS activity was greater in CL at day 4 than at day 9, and was also differently
      modulated by PGF-2alpha, depending on the age of the CL. The addition of PGF
      2alpha to day 4 CL had no effect, but PGF-2alpha on day 9 caused a threefold
      increase in NOS activity. NP caused a two- to fivefold decrease in release of
      progesterone from CL of both ages, and this inhibitory effect on steroidogenesis
      was reversed by l-NAME. All treatments failed to modify basal androgens and
      17beta-oestradiol was not detectable in either control or treated CL. These
      results suggest that NO is effectively involved in the regulation process of
      steroidogenesis, independently of 17beta-oestradiol. PGF-2alpha had no effect on
      day 4, but induced luteolysis on day 9, by reducing progesterone (P</=0. 01) to
      about 18% of control. The luteolytic action of PGF-2alpha was completely reversed
      by co-incubation with l-NAME, thus supporting the hypothesis that luteolysis is
      mediated by NO. The addition of NP or l-NAME did not modify the in vitro release
      of PGF-2alpha. We hypothesised that PGF-2alpha upregulates NOS activity and,
      consequently, the production of NO, which acutely inhibits progesterone release
      from day 9 CL of pseudopregnant rabbits.

PMID- 9924199
TI  - Effect of bacterial endotoxin on the in vitro release of Type II phospholipase-A2
      and prostaglandin E2 from human placenta.
AB  - The aim of this study was to establish the effect of bacterial endotoxin
      lipopolysaccharide (LPS) on the release of Type II phospholipase-A2 (PLA2) and
      prostaglandin E2 (PGE2) from late-pregnant human placental tissue incubated in
      vitro. Under basal conditions, immunoreactive Type II PLA2 and PGE2 were released
      from tissue explants in a time-dependent manner (up to 24 h, ANOVA, P<0. 0001,
      n=6). The release of these mediators was not associated with a loss of cell
      membrane integrity, as indicated by concentrations of the intracellular enzyme,
      lactate dehydrogenase (LDH), in the incubation medium. Incubation of explants in
      the presence of LPS (0. 001-100 microg LPS/ml) significantly decreased PLA2
      tissue content (P<0.02, n=6) and increased the accumulation of PLA2 and PGE2 in
      the incubation medium (P<0.0001, n=6). The data obtained in this study indicated
      that Type II PLA2 and PGE2 are released from term placenta under basal conditions
      and that LPS stimulated their release. The associated decrease in PLA2 tissue
      content is consistent with the hypothesis that LPS induces the release of stored
      PLA2. This study identifies one pathway by which products of bacterial infection
      may induce the release of a pro-inflammatory, extracellularly active PLA2 from
      intrauterine tissues that may promote the formation of phospholipid metabolites
      involved in the process of labour and delivery (e.g. the prostaglandins).

PMID- 9924200
TI  - Molecular forms of circulating adrenomedullin in patients with congestive heart
      failure.
AB  - In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)
      glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a
      biologically active mature form, AM(1-52)-NH2 (mAM), by enzymatic amidation. We
      recently reported that immunoreactive AM in human plasma consists of mAM and iAM.
      To clarify the pathophysiological roles of mAM and iAM in heart failure, we
      established an assay method to specifically detect mAM, and we determined the
      plasma concentrations of mAM and iAM in 68 patients with congestive heart failure
      (CHF). The plasma mAM concentrations of the CHF patients classified as being
      class I or II of New York Heart Association (NYHA) functional classification were
      significantly greater than those of the 28 healthy controls, and a further
      increase was noted in the class III or IV patients. Similar increases in plasma
      iAM were also observed in these patients compared with controls. The increased
      plasma mAM and iAM in 12 patients with exacerbated CHF were significantly reduced
      by treatment of their CHF for 7 days. In addition, the plasma concentrations of
      both mAM and iAM were significantly correlated with pulmonary capillary wedge
      pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio,
      heart rate, and the plasma concentrations of atrial and brain natriuretic
      peptides in the CHF patients. Thus the plasma concentrations of both mAM and iAM
      were increased progressively in proportion to the severity of CHF. These results
      suggest that, though the role of iAM remains to be clarified, mAM acts against
      the further deterioration of heart failure in patients with CHF.

PMID- 9924198
TI  - Glucose transporter 2 concentrations in hyper- and hypothyroid rat livers.
AB  - The deterioration of glucose metabolism frequently observed in hyperthyroidism
      may be due in part to increased gluconeogenesis in the liver and glucose efflux
      through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a
      facilitative glucose transporter localized to the liver and pancreas, may play a
      role in this distorted glucose metabolism. We examined changes in the levels of
      GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or
      methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An
      oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose
      tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats
      (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased
      in hyperthyroid rats and were not decreased in hypothyroid rats compared with
      euthyroid rats. The same results were obtained with a densitometric assay. These
      findings suggest that changes in the liver GLUT 2 concentration may contribute to
      abnormal glucose metabolism in thyroid disorders.

PMID- 9924201
TI  - Cellular distribution and ontogeny of insulin-like growth factors (IGFs) and IGF
      binding protein messenger RNAs and peptides in developing rat pancreas.
AB  - To determine the role of insulin-like growth factors (IGFs) and their binding
      proteins (IGFBPs) in the development of the pancreas, and specifically of the
      islets of Langerhans, we have examined the cellular distribution and
      developmental changes in the expression of IGFs and IGFBPs in the pancreas of the
      fetal and neonatal rat between 19.5 days of gestation and postnatal day 28. This
      represents a period of substantial growth and restructuring of the beta cell
      component in islets of this species. IGF-I, IGF-II, and IGFBPs-1 to -6 mRNAs were
      localized by in situ hybridization, and peptides by immunohistochemistry, in
      histological sections. IGF-II mRNA was highly expressed in islet cells and some
      ductal epithelial cells in late fetal and early neonatal life, but was barely
      detectable by postnatal day 28. IGF-II peptide showed a similar distribution. IGF
      I mRNA was barely detected in the fetus or neonate and was localized
      predominantly in the ductal and acinar tissues after postnatal day 7. IGF-I
      immunoreactivity was associated with some islet cells in the fetus and neonate,
      suggesting an endocrine rather than a paracrine source. We performed co
      localization studies to assess whether the distribution of IGFs within the
      pancreas might be due to a sequestration by locally produced IGFBPs. The presence
      of mRNAs for both IGFBPs-1 and -2 was minimal in the pancreas prior to postnatal
      day 7, although subsequently IGFBP-1 mRNA was seen in islet cells, while IGFBP-2
      mRNA was localized in both islets and acinar tissues. In contrast, both IGFBPs-1
      and -2 immunoreactivities were identified in islets from late fetal life,
      suggesting a circulatory source for these IGFBPs during early pancreatic
      development. IGFBPs-3 to -5 mRNAs and immunoreactivities were identified within
      islet cells throughout fetal and neonatal life, with IGFBPs-3 and -5 being mainly
      associated with the alpha cell-rich islet mantle. The results show a
      compartmentalization of IGFs within pancreatic tissue, reflecting both paracrine
      and endocrine sources. The localization and action of IGFs in pancreas likely
      involves sequestration and distribution by endogenous as well as circulating
      IGFBPs.

PMID- 9924203
TI  - Dietary advice in systemic sclerosis: the dangers of a high fibre diet.

PMID- 9924202
TI  - Intra-articular hyaluronan treatment for osteoarthritis.

PMID- 9924204
TI  - An overview of rheumatological research in the European Union.
AB  - OBJECTIVES: To evaluate the distribution and scope of papers published by authors
      from the European Union (EU) in rheumatological journals and the impact of
      rheumatological research in the EU in comparison with that produced elsewhere.
      METHODS: Papers published during the year 1995 in the 17 rheumatological journals
      screened by ISI were considered. The journal impact factor (IF) was noted. All
      key words, both those reported by the authors and those attributed by ISI, were
      identified and their frequency was calculated using a special purpose program.
      RESULTS: 2331 papers were published in the rheumatological literature during
      1995. Of them, 1316 (56.5%) came from the EU (29.4% from the UK, 17.4% from
      France, 11.5% from Germany, and 10.8% from Italy) and 544 (23.3%) from the USA.
      The mean IF of EU papers was approximately 2 in comparison with 3.5 for the USA
      and 2.4 for other countries. In 1995, 2680 key words attributed by the authors
      and 5651 attributed by ISI appeared in the rheumatological literature. Less than
      a quarter of them was cited more than twice. The leading key words were
      rheumatoid arthritis for diseases and methotrexate for drugs. CONCLUSIONS:
      Bibliometric findings are useful to follow research trends. These data show the
      relevance of EU rheumatological research and the high scientific production of
      small countries. Dispersion of key words should be avoided and journal editors
      should promote their standardisation.

PMID- 9924206
TI  - Improving musculoskeletal clinical skills teaching. A regionwide audit and
      intervention study.
AB  - OBJECTIVE: To identify factors that influence medical students' perceptions of
      the quality of a clinical skills course; to apply these factors to the course at
      one hospital; to measure the effect of this change. DESIGN: Cross sectional
      questionnaire survey; application of identified factors; repeat questionnaire
      survey. SETTING: Three teaching hospitals and five district general hospitals in
      north east England. SUBJECTS: Third year medical students attending locomotor
      clinical skills courses in two consecutive years. MAIN OUTCOME MEASURES: Score
      awarded by students in five categories; numbers of patients seen by each student;
      comparisons with other clinical skills weeks. RESULTS: Response rates were 71 of
      150 and 89 of 161. Factors associated with a high awarded score were:
      organisation of the course by a rheumatologist (p < 0.01); teaching from a
      rheumatologist (p < 0.01); higher number of patients seen (r = 0.76). Mean number
      of patients seen varied widely, from 7 per student at one hospital to 20.4 at
      another. Teaching hospitals scored poorly. In the second year, after making
      changes at one teaching hospital the mean total score improved (p < 0.01), and
      students saw more patients (p < 0.01). The ranking of this hospital rose from 6
      to 1. The additional cost of the modified course was 640 pounds per student.
      CONCLUSIONS: The standard of teaching of locomotor clinical skills varies widely
      and can be improved by application of factors identified in this survey, although
      additional costs are incurred.

PMID- 9924205
TI  - Estimating the burden of musculoskeletal disorders in the community: the
      comparative prevalence of symptoms at different anatomical sites, and the
      relation to social deprivation.
AB  - BACKGROUND: Epidemiologically-based rheumatology healthcare needs assessment
      requires an understanding of the incidence and prevalence of musculoskeletal
      disorders in the community, of the reasons why people consult in primary care,
      and of the proportion of people who would benefit from referral to secondary care
      and paramedical services. This paper reports the first phase of such a needs
      assessment exercise. SPECIFIC OBJECTIVE: To estimate the relative frequency of
      musculoskeletal pain in different, and multiple, anatomical sites in the adult
      population. SETTING: Three general practices in the former Tameside and Glossop
      Health Authority, Greater Manchester, UK, a predominantly urban area. DESIGN:
      Population survey. METHODS: An age and sex stratified sample of 6000 adults from
      the three practices was mailed a questionnaire that sought data on demographic
      factors, musculoskeletal symptoms (pain in the past month lasting for more than a
      week), and physical disability (using the modified Health Assessment
      Questionnaire--mHAQ). The areas of pain covered were neck, back, shoulder, elbow,
      hand, hip, knee, and multiple joints. The Carstairs index was used as a measure
      of social deprivation of the postcode sector in which the person lived. RESULTS:
      The response rate after two reminders was 78.5%. Non-responders were more likely
      to live in areas of high social deprivation. People who lived in more deprived
      areas were also more likely to report musculoskeletal pain, especially backpain.
      After adjusting for social deprivation the rates of musculoskeletal pain did not
      differ between the practices and so their results were combined. After adjustment
      for social deprivation, the most common site of pain was back (23%; 95% CI 21,
      25) followed by knee (19%; 95% CI 18, 21), and shoulder (16%; 95% CI 14, 17). The
      majority of subjects who reported pain had pain in more than one site. The
      prevalence of physical disability in the community rose with age. It was highest
      in those with multiple joint problems but was also high in those with isolated
      back or knee pain. CONCLUSION: Musculoskeletal pain is common in the community.
      People who live in socially deprived areas have more musculoskeletal symptoms.
      Estimates of the overall burden of musculoskeletal pain that combine the results
      of site specific surveys will be too high, those that do not adjust for
      socioeconomic factors will be too low.

PMID- 9924207
TI  - IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus.
AB  - OBJECTIVE: To ascertain the prevalence of IgE and non-IgE mediated allergic
      disorders in patients with systemic lupus erythematosus (SLE). METHODS: 49 SLE
      cases (all satisfying at least four "Revised ARA Criteria") and 98 healthy, age,
      and sex matched controls (randomly selected through two urban general practices
      and one rural general practice) were interviewed by telephone to screen for a
      history of allergy. Subjects with a history of allergic rhinitis, asthma or
      atopic eczema then underwent skin prick testing to confirm underlying IgE
      mediated disease. RESULTS: Analysis of the data by conditional logistic
      regression revealed no significant difference in frequency of allergic disorders
      in SLE cases and controls (odds ratio (OR) 0.92, 95% confidence intervals (CI)
      0.45, 1.86). In addition a subgroup analysis of subjects with IgE
      mediated/associated atopic disorders, showed that cases and controls were at a
      similar risk of having these conditions (OR 0.90, 95% CI 0.41, 1.96).
      CONCLUSIONS: This study suggests that people with SLE are not at an increased
      risk of IgE mediated/associated allergic disorders, in contrast with previous
      reports.

PMID- 9924208
TI  - Synovial mast cell responses during clinical improvement in early rheumatoid
      arthritis.
AB  - OBJECTIVES: To determine the synovial mast cell response in early rheumatoid
      arthritis (RA) during clinical improvement, and to examine for relations with
      clinical and histological parameters of disease activity. METHODS: Twenty two
      synovial samples were obtained from six patients with RA using needle
      arthroscopy. The mean disease duration at baseline was eight months, and two to
      three further samples were obtained over a mean follow up period of 15 months
      during which treatment initiated clinical improvement occurred. Sections were
      immunostained to detect MCT and MCTC mast cells and correlations were sought
      between clinical and histological data. RESULTS: The overall mean synovial mast
      cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast
      cells/mm2 in the superficial and deeper synovial layers respectively. The MCT
      subset predominated, outnumbering MCTC by 3:1. There was a significant
      correlation between the histological inflammation index and the MCT density, (r =
      0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant
      subset of mast cells varied in individual patient's synovia over time, with a
      trend towards restriction of the mast cell response to the superficial synovium
      during clinical improvement. CONCLUSIONS: The mast cell response in early RA is
      characterised by substantial expansion of predominantly MCT mast cells that
      correlates with histological indices of inflammation. During clinical
      improvement, this expansion tended to become more superficial. Taken together
      with previous studies of long duration RA, which implicate MCTC cells in synovial
      damage and disease progression, these results suggest that MCT and MCTC mast
      cells may possess distinct functions in the spectrum of inflammatory events
      occurring during RA.

PMID- 9924209
TI  - Influence of non-inherited maternal HLA-DR antigens on susceptibility to
      rheumatoid arthritis.
AB  - OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens
      (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased
      compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study
      was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in
      parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in
      97 RA patients and their parents. NIMA and NIPA frequencies were compared,
      stratified according to the presence of DR4 and/or the shared epitope (SE).
      RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4
      (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study
      this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of
      SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger
      than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36,
      13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4
      alleles and the susceptibility to RA was observed in two independent populations.

PMID- 9924210
TI  - The faux profil (oblique view) of the hip in the standing position. Contribution
      to the evaluation of osteoarthritis of the adult hip.
AB  - OBJECTIVE: The technique and results of a special oblique radiograph of the hip
      called the "faux profil" (FP) of the hip are described. The FP was evaluated for
      the detection of joint space narrowing in incipient osteoarthritis of the hip
      (OAH) as compared with the anteroposterior (AP) radiograph. METHODS: 58 hips with
      incipient osteoarthritis (joint space narrowing, 0-25% on the AP view) in 48
      patients were identified among 200 consecutive patients fulfilling American
      College of Rheumatology criteria for OAH. Joint space narrowing was measured on
      the AP and FP radiographs of these 58 hips. RESULTS: The FP view provides a true
      lateral projection of the femoral head and neck, and an oblique view of the
      acetabulum tangential to its superoanteromedial edge. On this view, the width of
      the anterosuperior and posteroinferior parts of the joint space can be measured
      and compared. Among the 58 hips with incipient OAH, 36 (62%) showed joint space
      narrowing on the AP view and 51 (91%) on the FP view. Among the 22 hips without
      joint space narrowing on the AP radiograph, 16 (72.7%) showed joint space
      narrowing on the FP view, involving the anterosuperior part of the joint in 11
      cases and the posteroinferior part in five cases. CONCLUSION: The FP view in the
      standing position should be used in incipient OAH as a complement to the AP view
      in patients with suspected OAH but no joint space narrowing on the AP radiograph.
      In this situation, nearly three quarters of hips in the study had joint space
      narrowing on the FP view, usually in the anterosuperior part and less often in
      the posteroinferior part of the joint.

PMID- 9924211
TI  - Mortality and causes of death in a Swedish series of systemic sclerosis patients.
AB  - OBJECTIVES: To analyse survival rates and the causes of death in a systemic
      sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant
      neoplasms and their possible association with oral cyclophosphamide (CYC)
      treatment. METHODS: Survival was calculated for 249 SSc patients followed up for
      up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 decreased
      patients were subdivided according to causes of death and its relation to SSc.
      Fatal malignancies in CYC treated patients were compared with those occurring in
      non-CYC treated patients. RESULTS: The overall 5 and 10 year survival rates were
      86% and 69% respectively. There was a 4.6-fold increased risk of death, as
      compared with the general population. Prognosis was worse in the diffuse
      cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous
      involvement (1SSc) and female subgroups. Of the 49 deaths, 24 were attributable
      to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension,
      pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the
      risk of dying of cancer. CONCLUSIONS: Mortality is increased both in the SSc
      population as a whole and in its different subsets (dSSc and 1SSc). Prognosis is
      worst among male patients with dSSc. However, the 5 year survival rate was better
      than those reported from earlier studies. Most patients die of cardiopulmonary
      disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused
      by chronic inflammatory disease of the lung. In this study, CYC treatment was not
      associated with an increased incidence of fatal malignant neoplasms.

PMID- 9924212
TI  - Treatment of staphylococcal septic arthritis in rabbits by systemic antibiotics
      and intra-articular corticosteroids.
AB  - OBJECTIVE: To assess the effect of intra-articular corticosteroids added to
      systemic antibiotics in experimental septic arthritis. METHODS: Rabbits were
      injected intra-articularly by Staphylococcus epidermidis. Rabbits received no
      additional treatment and served as control (group 1), were treated with systemic
      antibiotics (group 2), or treated with systemic antibiotics and intra-articular
      corticosteroids (group 3). After 15 days animals were killed and joint
      histopathological-histochemical parameters were assessed. RESULTS: All rabbits
      survived the experiment. The treated groups (2-3) had lower histological
      histochemical scores in comparison with the untreated group (1). Group 3 had
      significantly lower scores in joint sections in comparison with group 2: (mean
      (SD) 6.5 (1.4) v 4.0 (1.0), p = 0.001 and 7.4 (2.6) v 4.2 (2.2), p = 0.01),
      because of lower damage expressed in clustering of chondrocytes, pannus
      formation, proteoglycan depletion, and synovitis. CONCLUSION: Addition of local
      corticosteroids to systemic antibiotics in septic arthritis seems to be harmless,
      and improves joint histological-histochemical parameters in this experimental
      setting.

PMID- 9924214
TI  - Increased erythrocyte aggregation as an indicator for an aggressive clinical
      course in Behcet's disease: a prospective study.
AB  - OBJECTIVE: Changes in blood rheology, especially increased erythrocyte
      aggregation (EA) might play an important part in the development of arterial and
      venous thrombotic lesions. A prospective study was designed to evaluate EA in
      patients with Behcet's disease (BD) and to see if this parameter is predictive
      for the future development of vascular complications, such as deep vein
      thrombosis of various organ systems and uveitis. METHODS: EA was measured by a
      photometric Myrenne aggregometer in 38 patients with BD at the time of initial
      diagnosis and in 40 age and sex matched healthy controls (HC). RESULTS: During a
      median follow up period of 13.5 months, 13 patients developed vascular-ocular
      complications (eight deep vein thrombosis, nine uveitis, and four both deep vein
      thrombosis and uveitis). Patients were further divided into two groups: BD-a with
      mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular
      complications. EA values at high shear rate (M) and at low shear rate (M1) were
      compared among the groups. CONCLUSION: EA values at M and M1 were significantly
      higher in BD-b than BD-a and HC (p < 0.001). These results suggest that
      determination of EA rates might be useful to identify subgroups who are likely
      candidates for developing vascular-ocular complications in BD and management of
      factors known to affect blood rheology might be beneficial.

PMID- 9924213
TI  - T cell derived cytokines in psoriatic arthritis synovial fluids.
AB  - OBJECTIVE: The aim of this study was to investigate the concentrations of T cell
      derived cytokines in the synovial fluids (SFs) of patients with psoriatic
      arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis
      (OA). METHODS: Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor
      beta (TNF beta), and interferon gamma (INF gamma) and Th2 type cytokines (IL4,
      IL10) were measured by means of enzyme linked immunosorbent assays. RESULTS: IL2
      was usually not detectable in any of the disease groups. TNF beta was found in 3
      of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower
      concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p < 0.002). INF
      gamma was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p > 0.05). IL4 was
      present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of
      20 RA SFs (0.63 (0.09) pg/ml; p < 0.01). IL10 was found in 4 of 27 PsA SFs (12.3
      (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p < 0.0001). In all OA SFs
      cytokine concentrations were below the limit of detection. CONCLUSION: The
      pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs.
      However, both the frequency and the concentrations of cytokines were lower in PsA
      SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines
      altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs
      suggests the presence of activated T cells in the inflamed joint tissues and
      their participation in the immunoinflammatory events.

PMID- 9924215
TI  - Matrix metalloproteinase activity in equine synovial fluid: influence of age,
      osteoarthritis, and osteochondrosis.
AB  - OBJECTIVE: To investigate the influence of age, osteoarthritis (OA), and
      osteochondrosis (OC) on the matrix metalloproteinase (MMP) activity in the
      synovial fluid (SF) of equine joints. METHODS: SF was collected from normal and
      osteoarthritic metacarpophalangeal joints (normal: 14 adult, 28 juvenile; OA: 22
      adult). And from normal and osteochondrotic tarsocrural joints (5 months: 11
      normal, 8 OC; 11 months: 7 normal, 6 OC). Subsequently, overall MMP activity was
      measured. RESULTS: The level of active MMPs was almost twofold higher in SF from
      juvenile horses (age up to 11 months) than in SF from mature animals (4-30 years;
      p < 0.001). In juvenile horses MMP activity was higher in 5 month old foals than
      in 11 month old foals (p < 0.01). In adult horses MMP activity was independent of
      age. In OA joints the activity was nearly twice as high as in normal joints (p <
      0.001). In OC joints MMP activity was not significantly different from normal,
      age matched, control joints. CONCLUSIONS: MMP activity in SF from normal adult
      joints is not related to age. In juvenile joints MMP activity is significantly
      higher than activity in joints from adult animals. It is hypothesised that the
      gradual decrease in MMP activity with increasing age reflects the declining
      metabolic activity resulting from ceasing growth and the accompanying decrease in
      cartilage remodelling. The increased MMP activity in osteoarthritis joints most
      likely reflects matrix destruction. In osteochondrosis MMP mediated matrix
      degradation appears not to be different from normal joints.

PMID- 9924216
TI  - Disturbance of the menstrual pattern after local injection with triamcinolone
      acetonide.

PMID- 9924217
TI  - Molecular mechanisms of anaesthesia: light at the end of the channel?

PMID- 9924218
TI  - The Intensive Care Society and the British Journal of Anaesthesia.

PMID- 9924219
TI  - Sevoflurane pharmacokinetics: effect of cardiac output.
AB  - Sevoflurane uptake (Vsevo) can be predicted by the square root of time model or
      the four-compartment model. However, Vsevo and the effect of cardiac output on
      anaesthetic uptake have not been quantified clinically. After obtaining IRB
      approval and informed consent, 34 adult patients received closed-circuit
      anaesthesia with sevoflurane for 1 h. The end-expired sevoflurane concentration
      was maintained at 2.6% by infusion of liquid sevoflurane into the breathing
      system. In a subgroup of 12 patients, cardiac output was measured every 5 min by
      thermodilution (CO group). The effect of patient characteristics (age, height,
      weight, body surface area) and cardiac output on Vsevo were determined, and Vsevo
      was compared with the theoretical models. In the CO group, measured cardiac
      output was used in the formulae of these models. A two-exponential curve
      described average Vsevo well: Vsevo (ml liquid) = 0 + 1.62 x (1 - e(-2.3)xt) +
      18.1 x (1 - e(-0.0089xt), r2 > 0.999. There was no correlation between Vsevo and
      patient characteristics, except that Vsevo was greater in patients with a greater
      cardiac output (r2 = 0.36) and cardiac index (r2 = 0.35). The rate of sevoflurane
      uptake decreased less than predicted by the square root of time and four
      compartment models, even when measured cardiac output was used in the formulae.
      These findings confirm that the square root of time and four-compartment models
      do not accurately predict anaesthetic uptake. In addition, uptake of sevoflurane
      cannot be predicted by patient characteristics but was higher in patients with a
      higher cardiac output.

PMID- 9924220
TI  - Spinal anaesthesia for paediatric day-case surgery: a double-blind, randomized,
      parallel group, prospective comparison of isobaric and hyperbaric bupivacaine.
AB  - We have compared bupivacaine 5 mg ml-1, either isobaric in saline 0.9% or
      hyperbaric in 8% glucose, for spinal anaesthesia in 100 children, aged 2-115
      months, in a double-blind, randomized, parallel group, prospective study.
      Children were premedicated with diazepam 0.5 mg kg-1 orally. Seventy-two children
      were sedated before, and 25 children after, lumbar puncture, with either propofol
      or thiopental (thiopentone). After lumbar puncture in the lateral decubitus
      position with a 24-27-gauge paediatric spinal needle, isobaric or hyperbaric
      bupivacaine 5 mg ml-1 was injected in a dose of 0.3-0.5 mg kg-1 using a blinded
      procedure. Maximum cephalad extent of the block was tested by transcutaneous
      electrical stimulation. The success rate of the block was greater with hyperbaric
      bupivacaine (96%) compared with isobaric bupivacaine (82%) (P = 0.025, 95%
      confidence intervals (CI) 0-28%). Intense motor block was associated with
      adequate sensory block. Spread and duration of sensory block showed a similar
      wide scatter in both groups. The highest median level of sensory block was T4
      (range T1-12) in the isobaric group and T4 (T1-7) in the hyperbaric group. Times
      to two segment regression of block were similar: 80 (55-190) min in the isobaric
      and 80 (30-190) min in the hyperbaric group. Cardiovascular stability was good.
      Etilefrin was administered to one child to treat hypotension and atropine to one
      child to treat bradycardia. The study gave an impression of a delayed onset time
      of spinal block, as most of the nine children who required either fentanyl or a
      sedative for a mild reaction to skin incision had complete block when transferred
      to the recovery room after operation. Five children developed a mild, position
      dependent headache.

PMID- 9924221
TI  - Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1%
      bupivacaine with 0.0002% fentanyl for analgesia during labour.
AB  - We have compared analgesia during labour provided by two epidural drug regimens,
      in a double-blind, randomized, controlled study. Group A received 10-ml bolus
      doses of 0.1% bupivacaine with fentanyl 2 micrograms ml-1 while group B received
      0.25% plain bupivacaine 10 ml. Analgesia provided by both techniques was similar,
      but women in group A retained motor power in their legs and 60% chose to get out
      of bed. Duration of labour and time from insertion of the epidural to delivery
      was similar in both groups, but in group A, duration of the second stage was
      significantly shorter (P = 0.0003; 95% confidence interval (CI) -1.17, -0.27 h)
      and the incidence of forceps delivery was lower (P = 0.032). Maternal
      satisfaction with epidural analgesia, as assessed by VAS, was higher in group A
      (P = 0.04; 95% CI -0.001, 10.001).

PMID- 9924222
TI  - Local anaesthetic infiltration for surgical exodontia of third molar teeth: a
      double-blind study comparing bupivacaine infiltration with i.v. ketorolac.
AB  - We studied 40 patients undergoing surgical removal of at least two third molar
      teeth under general anaesthesia. Patients were allocated randomly to one of two
      groups: group B (n = 20) received bupivacaine up to 2 mg kg-1, infiltrated around
      the inferior alveolar nerves bilaterally, and group K (n = 20) received ketorolac
      10 mg i.v. at the start of surgery. There were no significant differences between
      the two groups in postoperative pain scores measured at 1 h using a visual
      analogue scale. Group K had a significantly lower incidence of side effects
      related to intraoral anaesthesia. Swallowing, speech and oral continence were
      significantly better. Group K scored higher for overall patient satisfaction,
      measured using a visual analogue scale. We failed to demonstrate any difference
      in early postoperative recovery (coughing, laryngospasm, stridor or arterial
      oxygen desaturation) between the groups. We conclude that the use of 0.5%
      bupivacaine infiltration was no more effective than a single 10-mg injection of
      ketorolac while giving rise to a higher rate of "minor" airway complications and
      lower patient acceptability.

PMID- 9924223
TI  - Differential onset of median nerve block: randomized, double-blind comparison of
      mepivacaine and bupivacaine in healthy volunteers.
AB  - We have compared the delay in onset of 1% mepivacaine and 0.33% bupivacaine in
      different nerve fibre types in 10 volunteers undergoing median nerve blocks, in a
      randomized, double-blind, crossover study. Hot, cold, pinprick and light touch
      sensations, compound motor action potentials (CMAP), sensory nerve action
      potentials (SNAP) and skin temperature were recorded at 2-min intervals. Hot,
      cold, pinprick, light touch sensations, SNAP and CMAP were significantly
      inhibited, and skin temperature was significantly increased after administration
      of both agents. The first noticeable reduction in cold sensation was detected
      later after bupivacaine compared with mepivacaine, but after a delay similar to
      that of other nerve functions. Bupivacaine and mepivacaine inhibited SNAP and
      CMAP with a similar time delay to steady-state. Bupivacaine produced steady-state
      inhibition of hot and cold sensations significantly later than mepivacaine;
      nevertheless, the sequence that sensory modalities failed, with few exceptions,
      and the extent of anaesthesia at 40 min were similar for both agents. Our
      technique provides a novel, multi-modal method of comparing local anaesthetics
      and related agents over time.

PMID- 9924224
TI  - Effect of anxiety on the rate of gastric emptying of liquids.
AB  - The efficacy of preoperative fasting is reduced in the presence of any factor
      which delays gastric emptying. We examined the association between anxiety and
      gastric emptying in adult patients undergoing elective surgery. Immediately
      before operation, 21 patients completed both a Spielberger state trait inventory
      (used to quantify current anxiety state (STAIs) and anxiety predisposition
      (STAIt)), and the Amsterdam preoperative anxiety and information scale (used to
      quantify anxiety and need for information). Gastric emptying was measured using
      the paracetamol absorption technique. Four to 10 weeks later, gastric emptying
      and STAI were measured again. Patients were more anxious before than after
      operation (STAIs = mean 35.4 (SD 10.9) and 25 (4.1), respectively; P = 0.0004).
      Neither anxiety state (P = 0.40) nor measures of anxiety relative to anxiety
      predisposition (P = 0.86) influenced gastric emptying (as measured by area under
      the paracetamol absorption-time curve). This contrasts with previous findings
      that anxiety in patients with low anxiety predisposition scores delays gastric
      emptying.

PMID- 9924225
TI  - Prophylactic antiemetic therapy with granisetron in women undergoing
      thyroidectomy.
AB  - We have evaluated the efficacy and safety of granisetron, a selective 5
      hydroxytryptamine type-3 receptor antagonist, for the prevention of postoperative
      nausea and vomiting (PONV) in women undergoing thyroidectomy. In a prospective,
      randomized, placebo-controlled, double-blind study, 100 ASA I patients, aged 30
      57 yr, received placebo or granisetron at three different doses (20, 40 or 100
      micrograms kg-1) (n = 25 each), i.v., immediately before induction of
      anaesthesia. A standard general anaesthetic technique was used. A complete
      response, defined as no PONV and no need for another rescue antiemetic during the
      first 3 h after anaesthesia, was seen in 36%, 44%, 92% and 92% of patients who
      received placebo, granisetron 20 micrograms kg-1, 40 micrograms kg-1 and 100
      micrograms kg-1, respectively; corresponding values during the next 21 h after
      anaesthesia were 40%, 44%, 88%, and 88% (P < 0.05; overall Fisher's exact
      probability test). There were no clinically important adverse events in any
      group. We conclude that granisetron 40 micrograms kg-1 was an effective
      antiemetic for the prevention of PONV after thyroidectomy. Increasing the dose to
      100 micrograms kg-1 provided no further benefit.

PMID- 9924226
TI  - Laser stimulation of acupuncture point P6 reduces postoperative vomiting in
      children undergoing strabismus surgery.
AB  - We conducted a double-blind, randomized, placebo-controlled study to investigate
      the effectiveness of P6 acupuncture on postoperative vomiting in children
      undergoing strabismus surgery. Acupuncture was performed by laser stimulation
      with a low-level laser. Laser stimulation of P6 was administered 15 min before
      induction of anaesthesia and 15 min after arriving in the recovery room. In the
      laser stimulation group, the incidence of vomiting was significantly lower (25%)
      than that in the placebo group (85%).

PMID- 9924227
TI  - Perioperative reliability of an on-site prothrombin time assay under different
      haemostatic conditions.
AB  - Perioperative use of laboratory coagulation assays is limited by the delay in
      obtaining results. The management of haemostasis during major surgical procedures
      requires rapid and accurate measurement of the prevailing coagulation status. In
      this prospective study, we have evaluated the reliability of on-site prothrombin
      time assessed by the portable coagulation monitor CoaguChek-Plus compared with
      standard laboratory assays during elective non-cardiac surgery. Sixty-two
      patients were assigned to one of three groups: group A = normal preoperative
      coagulation where minor intraoperative blood loss is expected; group B = normal
      preoperative coagulation where major intraoperative blood loss is expected; and
      group C = preoperative anticoagulation and minor intraoperative blood loss
      expected. On-site prothrombin time and laboratory prothrombin time showed poor
      correlation in group A (r2 = 0.24; bias (2 SD) 1.80 (3.34) S) and group B (r2 =
      0.30; 1.43 (3.12) S). The correlation in group C was better (r2 = 0.71; 1.41
      (1.92) S). We conclude that prothrombin time measured with the CoaguCheck-Plus
      monitor did not appear to be suitable for the management of haemostasis.

PMID- 9924228
TI  - Laryngeal mask airway and incidence of gastro-oesophageal reflux in paralysed
      patients undergoing ventilation for elective orthopaedic surgery.
AB  - We have studied the incidence of gastro-oesophageal reflux associated with the
      laryngeal mask airway (LMA) in 82 paralysed patients undergoing ventilation for
      elective orthopaedic surgery. Anaesthesia was managed by skilled LMA users. A pH
      sensitive probe was passed nasally into the oesophagus before induction and
      recordings made during five phases of anaesthesia. Anaesthesia was induced with
      propofol and fentanyl and maintained with 0.5-1.5% isoflurane and nitrous oxide
      in oxygen. Neuromuscular block was produced with vecuronium and the train-of-four
      count maintained at < or = 1. Towards the end of surgery, neuromuscular function
      was allowed to recover spontaneously. All LMAs were inserted at the first attempt
      and ventilation was successful in all patients. There were no adverse airway
      events. Mean oesophageal pH values during each phase of anaesthesia were: before
      insertion 5.88 (SD 0.77), placement 5.85 (0.74), maintenance 5.89 (0.73),
      emergence 5.71 (0.78) and removal 5.82 (0.75). There were no reflux events (pH <
      4.0) during any phase of anaesthesia. We conclude that the incidence of gastro
      oesophageal reflux is low in paralysed patients undergoing ventilation for
      elective orthopaedic surgery when antagonism of neuromuscular block is avoided.
      The validity of these findings for unskilled LMA users is unknown.

PMID- 9924229
TI  - Assessment of intubating conditions in adults after induction with propofol and
      varying doses of remifentanil.
AB  - We have assessed intubating conditions in three groups of 60 ASA I or II patients
      after induction of anaesthesia with propofol 2 mg kg-1 and remifentanil 0.5, 1.0
      or 2.0 micrograms kg-1. Tracheal intubation was graded according to ease of laryn
      goscopy, position of the vocal cords, coughing, jaw relaxation and movement of
      the limbs. Intubation was successful in 80%, 90% and 100% of patients after
      remifentanil 0.5, 1.0 or 2.0 micrograms kg-1, respectively. Overall intubating
      conditions were regarded as acceptable in 20%, 50% and 80% of patients,
      respectively. All three groups had a decrease in arterial pressure after
      induction but there was no difference between groups. The decrease in arterial
      pressure was not regarded as clinically significant. Intubating conditions were
      best after induction with remifentanil 2 micrograms kg and propofol 2 mg kg-1.

PMID- 9924230
TI  - Performance of proportional and continuous nitric oxide delivery systems during
      pressure- and volume-controlled ventilation.
AB  - We have evaluated the effect of delivering nitric oxide using a continuous flow
      system (CFS) or two commercially available proportional gas injection systems
      (PGIS), Nodomo (Drager, Lubeck, Germany) and Pulmonox-Mini (Messer Griesheim
      Austria, Gumpoldskirchen, Austria) on measured and simulated concentrations of
      nitric oxide. Nitric oxide concentration was measured in a bench test at five
      sites in the inspiratory breathing system during volume- or pressure-controlled
      ventilation and mathematically simulated using a mixing chamber model. For a
      target concentration of 10 parts per million (ppm) at the "Y" piece, simulated
      nitric oxide concentrations were 1.9-139 ppm for CFS, 0.3-22 ppm for the Nodomo
      and 0.0-31 ppm for the Pulmonox-Mini near the nitric oxide administration site.
      However, peak concentrations decreased rapidly along the inspiratory system.
      Measured and simulated variations depended on the nitric oxide delivery system,
      site of measurement and tidal volume. Measured variations were four times smaller
      in the Nodomo than in the Pulmonox-Mini and CFS. As inappropriate mixing may
      occur even with PGIS, nitric oxide should probably not be administered near the
      "Y" piece.

PMID- 9924231
TI  - Effects of dantrolene on the diaphragm muscle of the normal and myopathic
      hamster.
AB  - Dantrolene is the only known effective treatment for malignant hyperthermia.
      However, its effects on the myopathic diaphragm remain unknown. The effects of
      dantrolene 10(-8) to 10(-4) mol litre-1 on diaphragm muscle strips in normal (n =
      12) and myopathic hamsters (n = 13) were investigated in vitro in response to
      tetanic stimulation. We studied contraction under isotonic and isometric
      conditions. Data are presented as mean (SD) percent of baseline. Dantrolene
      induced a negative inotropic effect in normal and myopathic hamsters but no
      significant difference was observed between groups (active force at 10(-4) mol
      litre-1; 34 (7) vs 32 (11)%; ns). We conclude that dantrolene induced a
      comparable negative inotropic effect on diaphragm muscle in normal and myopathic
      hamsters.

PMID- 9924232
TI  - Critical haemoglobin concentration in anaesthetized dogs: comparison of two
      plasma substitutes.
AB  - We have explored systemic and regional tolerance to haemodilution during
      anaesthesia with two different synthetic colloids. Eighteen dogs undergoing
      mechanical ventilation during anaesthesia with ketamine were submitted to
      progressive normovolaemic haemodilution with either gelatin (GEL; n = 9) or
      hydroxyethylstarch (HES; n = 9) administered on a 1:1 ratio. Systemic oxygen
      delivery was calculated from measurement of thermodilution cardiac output and
      arterial oxygen content, while systemic oxygen consumption was determined from
      expired gas analysis. Mesenteric oxygen delivery and consumption were determined
      using ultrasonic flow measurements, and arterial and mesenteric venous oxygen
      contents. The critical haemoglobin concentration (i.e. the haemoglobin value
      below which oxygen consumption becomes oxygen delivery dependent) was mean 3.6
      (SD 0.8) g dl-1 in the GEL and 3.5 (1.5) g dl-1 in the HES group. The mesenteric
      critical oxygen extraction ratio (O2ER) (GEL 50.1 (12.1)%; HES 48.5 (13.4)%) was
      significant lower than the systemic critical O2ER (GEL 66.1 (8.4)%; HES 67.7
      (7.1)%). There were no significant differences between the GEL and HES groups for
      any of these variables, or in the amount of colloid administered. During the
      study, oxygen delivery decreased almost linearly with reduction in haemoglobin,
      indicating a lack of cardiac output response to anaemia during ketamine
      anaesthesia.

PMID- 9924233
TI  - Suppression of parasympathetic reflex vasodilatation in the lower lip of the cat
      by isoflurane, propofol, ketamine and pentobarbital: implications for mechanisms
      underlying the production of anaesthesia.
AB  - We have compared the effects of isoflurane, propofol, ketamine and pentobarbital
      on parasympathetic reflex vasodilatation to investigate their involvement in GABA
      mediated synaptic inhibition, enhancement of which is thought to underlie the
      action of many anaesthetic agents. In cats anaesthetized with urethane-alpha
      chloralose, parasympathetic reflex vasodilation in the ipsilateral lower lip was
      elicited by electrical stimulation of the central cut end of the lingual nerve.
      Isoflurane and pentobarbital both produced marked dose-dependent inhibition of
      this vasodilator response. In contrast, propofol and ketamine had no effect on
      parasympathetic reflex vasodilation. Administration of a GABA antagonist
      (picrotoxin) reversed the inhibition produced by isoflurane (previous results)
      and pentobarbital (present study). Our results suggest that isoflurane and
      pentobarbitone inhibit parasympathetic reflex vasodilatation via a GABA-mediated
      mechanism, but that propofol and ketamine have no such effect. Our results with
      propofol cast doubt on its presumed mechanism of action as an anaesthetic.

PMID- 9924234
TI  - Volatile anaesthetics have differential effects on recombinant m1 and m3
      muscarinic acetylcholine receptor function.
AB  - Muscarinic acetylcholine signalling plays major roles in regulation of
      consciousness, cognitive functioning, pain perception and circulatory
      homeostasis. Halothane has been shown to inhibit m1 muscarinic signalling.
      However, no comparative data are available for desflurane, sevoflurane or
      isoflurane, nor have the anaesthetic effects on the m3 subtype (which is also
      prominent in the brain) been studied. Therefore, we have investigated the effects
      of these compounds on isolated m1 and m3 muscarinic receptor function.
      Defolliculated Xenopus oocytes expressing recombinant m1 or m3 muscarinic or (for
      comparison) AT1A angiotensin II receptors were voltage clamped, and Ca(2+)
      activated Cl- currents (ICl(Ca)) induced by acetyl-beta-methylcholine (Mch) or
      angiotensin II were measured in the presence of clinically relevant
      concentrations of halothane, sevoflurane, desflurane or isoflurane. To determine
      the site of action of the volatile anaesthetics we compared anaesthetic effects
      on m1, m3 and AT1A receptor function and studied the effects of volatile
      anaesthetics on signalling induced by intracellular injection of the second
      messenger IP3. Desflurane had a biphasic effect on m1 signalling, enhancing at a
      concentration of 0.46 mmol litre-1 but depressing at 0.92 mmol litre-1. A
      similar, although not significant, trend was observed with m3 signalling.
      Isoflurane had no effect on m1 signalling, but profoundly inhibited m3
      signalling. Sevoflurane depressed the function of m1 and m3 signalling in a dose
      dependent manner. Halothane, similar to its known effect on m1 signalling, dose
      dependently depressed m3 function. ICl(Ca) induced by intracellular injections of
      IP3 were unaffected by all four anaesthetics. Similarly, none of the anaesthetics
      tested affected AT1A signalling. Absence of interference with AT1A signalling and
      intracellular pathways suggest that the effects of anaesthetics on muscarinic
      signalling most likely result from interactions with the m1 or m3 receptor
      molecule. Multiple interaction sites with different affinities may explain the
      biphasic response to desflurane. Anaesthetic-specific effects on closely related
      receptor subtypes suggest defined sites of action for volatile anaesthetics on
      the receptor protein.

PMID- 9924235
TI  - Effects of isoflurane on receptor-operated Ca2+ channels in rat aortic smooth
      muscle.
AB  - We have investigated the effects of isoflurane on receptor-operated Ca2+ channels
      (ROC) in vascular smooth muscle. In isolated rat thoracic aortic rings denuded of
      endothelium, the effects of isoflurane on phenylephrine-induced contraction and
      Ca2+ influx were evaluated in the presence of supramaximal doses of nifedipine or
      verapamil. Under isometric tension recording, the aortic rings were precontracted
      by phenylephrine 300 nmol litre-1 and exposed to 1.2%, 2.3% or 3.5% isoflurane.
      Phenylephrine-induced precontraction was enhanced with 2.3% isoflurane by mean
      8.1 (SD 9.3)% (P < 0.05 vs 0% isoflurane). The constrictor effect of 2.3%
      isoflurane was not inhibited by depletion of intracellular Ca2+ stores with
      ryanodine 20 mumol litre-1, but was abolished in a Ca(2+)-free solution or by
      SK&F 96,365 30 mumol litre-1, an ROC blocker. Isoflurane-induced contraction was
      accompanied by increased intracellular free Ca2+ concentration, monitored using
      fura PE3. Unidirectional 45Ca2+ influx measurement in phenylephrine-stimulated
      aortic strips revealed that the mean amount of Ca2+ influx was significantly (P <
      0.05) enhanced by 1.2% and 2.3% isoflurane, which were 117.1% and 119.7% of
      control values, respectively. Our results strongly suggest that isoflurane
      enhanced Ca2+ influx through ROC that had been submaximally activated by
      phenylephrine.

PMID- 9924236
TI  - Antioxidant effects of propofol in human hepatic microsomes: concentration
      effects and clinical relevance.
AB  - Propofol is known to possess antioxidant properties. There is controversy
      regarding the mechanisms by which the drug produces its antioxidant effects and
      the significance of these effects in relation to plasma concentrations of
      propofol in clinical practice. We studied the effects of increasing
      concentrations of Intralipid, propofol, butylated hydroxytoluene (BHT) and a
      vitamin E analogue (Trolox C) in 0.9% saline on non-enzymic and enzymic lipid
      peroxidation in human hepatic microsomes, and on concentrations of antioxidant
      enzymes in a Hep G2 cell line. Propofol showed significant inhibition of lipid
      peroxidation, but was less potent than BHT or Trolox C. IC50 values for non
      enzymic and enzymic lipid peroxidation were mean 9.47 (SD 0.86) and 7.39 (0.84)
      mumol litre-1 for propofol, 1.30 (0.57) and 0.32 (0.02) mumol litre-1 for BHT and
      2.34 (0.68) and 0.35 (0.04) mumol litre-1 for Trolox C, respectively. The
      antioxidant activities of propofol were substantially retained in the presence of
      up to 30 g litre-1 of human serum albumin. Propofol at concentrations of up to
      100 mumol litre-1 had no significant effect on the activities of antioxidant
      enzymes. Clinically relevant concentrations of propofol produced significant
      inhibition of both enzymic and non-enzymic lipid peroxidation in hepatic
      microsomal preparations, possibly as a result of accumulation in lipophilic
      environments. Measurement of antioxidant effects of drugs in aqueous media may
      have little relevance to their effects in protecting against lipid peroxidation
      in biological systems.

PMID- 9924237
TI  - Continuous spinal anaesthesia.

PMID- 9924238
TI  - The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v.
      fentanyl.
AB  - We studied 10 healthy volunteers given itraconazole 200 mg orally, once daily or
      placebo for 4 days in a crossover study. i.v. fentanyl 3 micrograms kg-1 was
      given on day 4. Plasma concentrations of fentanyl were measured by
      radioimmunoassay and ventilatory frequency and peripheral arteriolar oxygen
      saturation were also measured. Fentanyl-induced subjective effects (drowsiness,
      itching, nausea, performance, feeling of drug effect) were measured by visual
      analogue scales. The pharmacokinetics and pharmacodynamics of fentanyl were
      similar after both itraconazole and placebo. Thus although itraconazole is a
      strong inhibitor of the cytochrome 3A enzymes responsible for metabolism of
      fentanyl in vitro, it did not affect the i.v. pharmacokinetics of fentanyl in
      humans.

PMID- 9924239
TI  - Thiopental attenuates relaxation and cyclic GMP production in vascular smooth
      muscle of endotoxin-treated rat aorta, independent of nitric oxide production.
AB  - As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by
      nitric oxide donor drugs, we have tested if it suppresses cGMP formation and
      increases vascular tone after induction of calcium-calmodulin-independent nitric
      oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli
      lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental
      on tension, cGMP concentrations and nitrite accumulation were determined.
      Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted
      aortic rings before LPS treatment, but caused no significant effects on tension
      in the presence of L-arginine 10 mumol litre-1 after LPS treatment. L-Arginine 1
      mumol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated
      aorta in a concentration-dependent manner. This was reduced by thiopental 0.3-1
      mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations
      of nitrite, the end product of nitric oxide; this was not affected by thiopental
      1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS
      induced vascular smooth muscle without affecting nitric oxide production.

PMID- 9924240
TI  - Patient-controlled interscalene analgesia with ropivacaine after major shoulder
      surgery: PCIA vs PCA.
AB  - We have compared the efficacy of patient-controlled interscalene analgesia (PCIA)
      using ropivacaine with patient-controlled analgesia (PCA) using nicomorphine in
      60 patients (n = 30 in each group), in a prospective, randomized study. In both
      groups, all patients received interscalene block with 0.75% ropivacaine before
      induction of anaesthesia. Six hours after interscalene block, patients in group
      PCIA received continuous infusion of 0.2% ropivacaine at a rate of 5 ml h-1 with
      a bolus dose of 3 or 4 ml and a lockout time of 20 min; patients in group PCA
      received continuous infusion of nicomorphine 0.5 mg h-1 and a bolus dose of 2 or
      3 mg with a lockout time of 20 min. Control of pain was significantly better from
      12 to 48 h after operation (except at 42 h) in group PCIA. Nausea and pruritus
      occurred significantly more frequently in group PCA. Patient satisfaction was
      greater in group PCIA. We conclude that the use of 0.2% ropivacaine using PCIA
      was an efficient way of managing pain after major shoulder surgery and compared
      favourably with PCA nicomorphine in terms of pain relief, side effects and
      patient satisfaction.

PMID- 9924242
TI  - Airway control during percutaneous dilatational tracheostomy: pilot study with
      the intubating laryngeal mask airway.
AB  - Percutaneous dilatation tracheostomy has become a common procedure for bedside
      insertion of tracheostomy tubes in the intensive care unit. Management of the
      airway during the procedure using the laryngeal mask airway (LMA) and other
      methods has been described. The intubating laryngeal mask airway has several
      potential benefits for airway management during percutaneous dilatation
      tracheostomy compared with the LMA. These include the use of both the fibreoptic
      bronchoscope and tracheal tube if necessary. We report the results of a pilot
      study of 10 patients that illustrates these advantages.

PMID- 9924241
TI  - Remifentanil prevents an increase in intraocular pressure after succinylcholine
      and tracheal intubation.
AB  - We have studied changes in intraocular pressure (IOP) in 30 patients after
      succinylcholine (suxamethonium) and tracheal intubation following administration
      of propofol 2 mg kg-1 and either remifentanil 1 microgram kg-1 (group R) or
      saline (group S). IOP was measured before induction, before administration of
      succinylcholine and the study drug, before intubation and for every 1 min after
      intubation for 5 min. There was a significant decrease in IOP in group R compared
      with group S from the time of administration of the study drugs to the end of the
      study (P < 0.006).

PMID- 9924243
TI  - The intubating laryngeal mask airway (ILMA): initial experience in Singapore.
AB  - We have evaluated the intubating laryngeal mask airway (ILMA) for ventilation and
      for blind tracheal intubation. After induction of anaesthesia with fentanyl 1
      microgram kg-1 and propofol 3 ml kg-1, the ILMA was placed successfully on the
      first attempt in all 100 patients. After administration of atracurium 0.5 mg kg
      1, blind tracheal intubation was successful in 97% of patients--50% on the first
      attempt, 42% on the second and 5% on the third. Success was improved by pulling
      the metal handle of the ILMA towards the intubator in an "extension" manoeuvre,
      if intubation was not possible on the first attempt. These findings confirm the
      effectiveness of the ILMA in an Asian population.

PMID- 9924244
TI  - Laryngotracheal separation after attempted hanging.
AB  - The successful management of a 29-yr-old patient with tracheal separation between
      rings one and two after attempted hanging is described. Increasing difficulty
      with ventilation via a tracheal tube and surgical emphysema indicated the need
      for a tracheostomy. The diagnosis was made during the tracheostomy procedure when
      it was observed that the tracheal tube was protruding through the incomplete
      transection of the trachea such that Murphy's eye was aligned with the lower
      tracheal stump. The patient underwent primary anastomosis of the trachea with
      placement of a Lorenz tracheal stent. On subsequent follow-up he had evidence of
      damage to both recurrent laryngeal nerves. The signs and symptoms of
      laryngotracheal separation after blunt trauma are described. A review of the
      airway management has been made as it requires combined anaesthetic and surgical
      expertise. Injuries to the trachea may have severe, life-threatening consequences
      and early diagnosis and management reduce morbidity and mortality.

PMID- 9924245
TI  - A complication of peribulbar block in a patient with exophthalmos.
AB  - A patient with marked exophthalmos secondary to thyroid eye disease presented for
      tarsorrhaphy and removal of orbital fat. A single superolateral peribulbar
      injection was performed. After injection of 3.5 ml of local anaesthetic solution,
      the globe suddenly dislocated anteriorly. This complication has not been
      described previously. In patients with exophthalmos, general anaesthesia should
      be considered as the method of choice for ophthalmic procedures.

PMID- 9924246
TI  - Pituitary apoplexy after spinal anaesthesia.
AB  - We report the case of a previously healthy 51-yr-old male who underwent an
      uneventful total hip replacement under spinal anaesthesia. His immediate
      postoperative course was complicated by the development of a severe frontal
      headache. Initial conservative treatment included oral analgesics and an epidural
      blood patch. The headache persisted and was followed by progressive vision loss
      and a right partial third nerve palsy. The patient was almost blind at the time
      of transfer to our neurosurgical unit. Relevant investigations revealed marked
      hyponatraemia (serum sodium concentration 122 mmol litre-1) and second-degree
      heart block (Mobitz I). A CT scan showed a pituitary tumour and confirmed the
      clinical diagnosis of pituitary apoplexy. Urgent craniotomy was scheduled and a
      large necrotic pituitary adenoma was excised. The postoperative course was
      uneventful with return of near normal vision at the time of discharge. Clinicians
      should consider this diagnosis when focal neurological deficits occur with post
      dural puncture headache.

PMID- 9924247
TI  - Epidural anaesthesia for caesarean section in an achondroplastic dwarf.
AB  - We describe the anaesthetic management of a parturient with achondroplasia
      presenting for Caesarean section under epidural anaesthesia. A block extending
      from T4 to S4 was established over 25 min using a total of 12 ml of 2.0%
      lidocaine (lignocaine) with epinephrine (adrenaline) 1:200,000 and fentanyl 37.5
      micrograms. Apart from mild discomfort during peritoneal incision, her
      perioperative course was uneventful. Achondroplasia is reviewed and the
      anaesthetic implications of the condition are discussed.

PMID- 9924248
TI  - Transient radicular irritation after spinal anaesthesia with 2% isobaric
      mepivacaine.
AB  - Several cases have been reported in which symptoms suggestive of transient
      radicular irritation occurred after the use of lidocaine (lignocaine) for spinal
      anaesthesia. We report three patients in whom we observed similar symptoms after
      uneventful spinal anaesthesia using isobaric 2% mepivacaine.

PMID- 9924249
TI  - Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium.
      1975.

PMID- 9924250
TI  - Propofol and postoperative nausea and vomiting.

PMID- 9924251
TI  - Anaesthesia in Third World countries.

PMID- 9924253
TI  - Practical airway assessment.

PMID- 9924252
TI  - Current practice of local anaesthesia for ocular surgery.

PMID- 9924254
TI  - Anaesthetic for telescopic procedures in the thorax.

PMID- 9924255
TI  - Appropriate size of the laryngeal mask airway in adults.

PMID- 9924256
TI  - Appropriate size of the laryngeal mask airway in adults.

PMID- 9924257
TI  - Paddle size in defibrillation.

PMID- 9924258
TI  - An extrapyramidal reaction to ondansetron.

PMID- 9924259
TI  - Postdural puncture headache after combined spinal-epidural analgesia and
      anaesthesia.

PMID- 9924260
TI  - Pharmacokinetics of propofol during conscious sedation using target-controlled
      infusion.

PMID- 9924261
TI  - Dietary factors and postprandial lipaemia.

PMID- 9924262
TI  - The effect of acute carbohydrate load on the monophasic or biphasic nature of the
      postprandial lipaemic response to acute fat ingestion in human subjects.
AB  - Previous studies in this laboratory have elicited a monophasic response in
      postprandial plasma triacylglycerol (TAG) level with fat intakes of 0.5 g fat/kg
      body weight accompanied by about 17 g carbohydrate as lactose. Recent studies
      involving the same level of fat with a higher level of carbohydrate, 136 g of
      which 60 g was sucrose, appeared to elicit a biphasic response. The present study
      compared these two test meals and showed a significant meal x time interaction
      for plasma total TAG (P = 0.0228) reflecting a monophasic response with the lower
      carbohydrate test meal. The higher-carbohydrate meal induced significantly higher
      insulin and glucose-dependent insulinotropic polypeptide responses (P = 0.0009
      and P = 0.0041 respectively). A significant meal x time interaction was seen for
      plasma non-esterified fatty acids (P = 0.0437). The biphasic plasma TAG response
      seen with the high-carbohydrate meal largely reflected the TAG-rich lipoprotein
      (TRL) or chylomicron fraction, which would tend to suggest a biphasic pattern of
      absorption. This was borne out by TRL-TAG fatty acid compositions. Both peak in
      the biphasic response showed active incorporation of the main dietary fatty
      acids, 18:1n-9, 18:2n-6 and 18:3n-3 into TRL-TAG. These results indicate that
      under the specific test-meal conditions used in the present study, a biphasic
      pattern of fat absorption was seen.

PMID- 9924263
TI  - African plant foods rich in non-starch polysaccharides reduce postprandial blood
      glucose and insulin concentrations in healthy human subjects.
AB  - The effects of two vegetable flours, prepared from the African plants Detarium
      senegalense Gmelin, a legume, and Cissus rotundifolia, a shrub, on postprandial
      blood glucose and insulin concentrations in human subjects, were investigated.
      Chemical analysis indicated that these flours contained significant amounts of
      NSP. The detarium in particular was found to be a rich source of water-soluble
      NSP (SNSP). The flours were incorporated into two types of breakfast meal, a stew
      meal and a wheat bread meal, containing 50 g and 70 g available carbohydrate
      respectively. Both meals also contained 10-12 g NSP, the major fraction of which
      was SNSP. Control and fibre-rich meals were consumed on separate days in
      randomized order by two different groups of subjects (n 5, stew meals; n 10,
      bread meals). Venous blood samples were taken at fasting (0 min) and
      postprandially at 30 min intervals for 2.5 h and the plasma analysed for glucose
      and insulin. Compared with the controls, detarium and cissus meals elicited
      significant reductions (P < 0.006) in plasma glucose levels at most postprandial
      time points and for area-under-the-curve (AUC) values (AUC reductions 38-62%).
      Significant reductions (P < 0.002) in plasma insulin levels at various
      postprandial time points and for AUC values were also seen after detarium and
      cissus breads (AUC reductions 43 and 36% respectively), but not after the fibre
      rich stew meals. SNSP and starch are possibly the main, but not the only,
      components responsible for the glucose- and insulin-lowering effects of cissus
      flour. The main SNSP fraction of detarium, identified as a high-molecular-weight
      xyloglucan, is likely to be a primary factor in determining the physiological
      activity of detarium flour.

PMID- 9924264
TI  - Physical and chemical transformations of cereal food during oral digestion in
      human subjects.
AB  - Chemical and physical transformations of solid food begin in the mouth, but the
      oral phase of digestion has rarely been studied. In the present study, twelve
      healthy volunteers masticated mouthfuls of either bread or spaghetti for a
      physiologically-determined time, and the levels of particle degradation and
      starch digestion before swallowing were compared for each food. The amounts of
      saliva moistening bread and spaghetti before swallowing were, respectively, 220
      (SEM 12) v. 39 (SEM 6) g/kg fresh matter. Particle size reduction also differed
      since bread particles were highly degraded, showing a loss of structure, whereas
      spaghetti retained its physical structure, with rough and incomplete reduction of
      particle size. Starch hydrolysis was twice as high for bread as for spaghetti,
      mainly because of the release of high-molecular-mass alpha-glucans. The
      production of oligosaccharides was similar after mastication of the two foods,
      respectively 125 (SEM 8) and 92 (SEM 7) g/kg total starch. Starch hydrolysis,
      which clearly began in the mouth, depended on the initial structure of the food,
      as in the breakdown of solid food. These significant physical and chemical
      degradations of solid foods during oral digestion may influence the entire
      digestive process.

PMID- 9924265
TI  - The effect of short-term calcium supplementation on biochemical markers of bone
      metabolism in healthy young adults.
AB  - The influence of Ca supplementation of the usual diet for 14 d on biochemical
      markers of bone turnover was investigated in healthy young adults aged 21-26
      years. In a crossover study, eighteen subjects (five male and thirteen female)
      were randomly assigned to their self-selected diet (about 22 mmol Ca/d) or their
      self-selected diet with a 20 mmol/d Ca supplement (about 40 mmol Ca/d) for 14 d
      followed by crossover to the alternative diet for a further 14 d. During each
      dietary period fasting morning first void urine samples (last 3 d) and fasting
      blood serum samples (morning of twelfth day) were collected. Ca supplementation
      reduced urinary excretion of pyridinoline (14%) and deoxypyridinoline (16%)
      (biochemical markers of bone resorption) but had no effect on biochemical markers
      of bone formation (serum osteocalcin and bone-specific alkaline phosphatase; EC
      3.1.3.1). It is concluded that Ca supplementation of the usual diet in young
      adults suppresses bone resorption over a 2-week period. If sustained, this could
      result in suppression of the bone remodelling rate and an increase in bone mass
      over time. The findings of this short-term study with a relatively small number
      of young adults highlight the need for a longer-term intervention study of the
      effect of increased Ca intake on bone mass in this age group.

PMID- 9924267
TI  - Maternal reports of child illness and the biochemical status of the child: the
      use of morbidity interviews in rural Bangladesh.
AB  - In a longitudinal study of child growth and nutritional status in Bangladesh,
      child morbidity was recorded using health interviews with the mother. The aim of
      the present study was to establish whether maternal reports of child illness were
      associated with the biochemical health status of the child. Children aged 2-5
      years (n 117) took part in the study and their mothers were interviewed every
      fortnight by Bangladeshi fieldworkers. Maternal reports of diarrhoea were
      associated with significantly lower plasma albumin concentrations (P < 0.001),
      poorer intestinal permeability (P < 0.001), higher plasma immunoglobulin A levels
      (P < 0.005) and higher alpha-1-antichymotrypsin (ACT) levels (P < 0.05) compared
      with children reported to be healthy. Children with fever had significantly
      higher ACT (P < 0.001) and lower albumin (P < 0.05) levels compared with their
      healthy counterparts. Respiratory infections (RI) were not associated with any
      significant changes; however, reports of RI with fever were associated with
      significantly higher levels of ACT than either illness individually (interaction
      P < 0.05). These highly significant associations between maternal reports of
      illness and biochemical profiles of child health support the use of health
      interviews in developing countries.

PMID- 9924266
TI  - Lutein ester in serum after lutein supplementation in human subjects.
AB  - Lutein, one of the major carotenoids present in serum, is also widely consumed by
      most populations. For the purpose of testing the potential health benefits of
      several carotenoids, lutein was supplied as part of an intervention trial to test
      whether the consumption of these food constituents reduces oxidative damage to
      human tissue components. Lutein from a natural source (15 mg/d as mixed ester
      forms) was supplied for 4 months to eighteen non-smoking, apparently healthy
      volunteers (nine men, nine women) aged 25-45 years. The serum carotenoid profile
      was analysed at baseline and monthly thereafter. On average, lutein
      concentrations increased 5-fold after the first month of supplementation (mean
      1.34 (range 0.6-3.34) mumol/l). On reviewing the results, in those volunteers
      whose lutein levels surpassed 1.05 mumol/l (fourteen of seventeen), we
      tentatively identified lutein monopalmitate along with another unidentified ester
      (possibly from a monoketocarotenoid) in serum. Lutein levels returned to baseline
      values and ester forms were not present 3 months after supplementation was
      discontinued. Their concentrations did not correlate with, and represented less
      than 3% of, lutein levels achieved in serum. They were observed before
      development of, and despite the presence of, carotenodermia. To our knowledge,
      this is the first time xanthophyll esters have been described in human serum. In
      view of the fact that xanthophyll esters have not been previously reported in
      serum and chylomicrons, it seems unlikely that these ester forms would be a
      reflection of the contents of the capsule. They may indicate a 'ceiling effect'
      on or saturation of the transport capacity for xanthophylls, and may have been re
      esterified in vivo because of the unusual dietary conditions. The determination
      of the physiological importance of this finding will require further
      investigation, although neither haematological nor biochemical changes were
      detected.

PMID- 9924268
TI  - Intestinal degradation in pigs of rye dietary fibre with different structural
      characteristics.
AB  - In order to investigate the effects of dietary fibre (DF) characteristics on
      carbohydrate degradation and the metabolism in the large intestine, pigs were fed
      on four rye-bread diets (based on whole rye, pericarp/testa, aleurone or
      endosperm) with differences in characteristics and amount of DF. The
      degradability of DF in the large intestine varied greatly between diets. The
      pericarp/testa DF was hardly degraded in the large intestine, whereas endosperm
      DF was extensively and rapidly degraded in the caecum. Caecal degradation of
      aleurone DF was also limited, leaving more material to be degraded in the colon.
      The undegradable pericarp/testa DF was characterized by high contents of lignin,
      cellulose, ferulic acids and highly substituted arabinoxylans (the major DF
      component in rye). Ingestion of this diet resulted in increased faecal bulk and
      reduced transit time, but with low colonic pH and the lowest concentrations of
      shortchain fatty acids (SCFA). The aleurone diet, on the other hand, led to a
      fermentation pattern which may be considered more optimal, with lower colonic pH
      and higher concentrations of SCFA, in particular butyric acid. Despite the large
      differences in carbohydrate fermentation only minor significant effects on the
      presence of protein degradation products and on histological measurements (height
      and diameter of colonic crypts and thickness of the muscularis external) were
      observed.

PMID- 9924269
TI  - Caecal fermentation and energy accumulation in the rat fed on indigestible
      oligosaccharides.
AB  - The energetic contribution from, and effects on the gastrointestinal tract of,
      indigestible oligosaccharides in growing rats were compared with those of sucrose
      (S). S and two types of oligosaccharides, fructo-oligosaccharide (Fru) and 6'
      galacto-oligosaccharide (Gal) were added to a basal diet at a level of 100 g/kg.
      The basal diet was given either ad libitum (group B) or at a level approximately
      90% of the ad libitum intakes of the Fru and Gal groups (group BR). During a 50 d
      feeding period, feed intake, digestibilities of nutrients, and digesta retention
      times using liquid (Co-EDTA) and particulate (Cr-cell-wall constituents) markers
      were measured. The carcass and the contents of the stomach and caecum were
      sampled on the last day of the experimental period. There was no significant
      difference in feed intake between groups other than BR. Addition of Fru and Gal
      to the basal diet resulted in increased crude ash digestibility and decreased
      crude protein and fat digestibilities. Mean retention times of digesta markers
      were increased by addition of Fru and Gal to the diet, and this was associated
      with enlargement of the caecum. Concentrations and amounts of total organic acids
      in the caecum were higher in groups Fru and Gal than the other groups. The amount
      of energy accumulated in the carcass of rats in the Gal group was significantly
      (P < 0.05) lower than that of rats fed on S but not Fru. Contributions to energy
      accumulation tended to be different between Fru and Gal; these were associated
      with differences in composition of caecal organic acids and of fatty acids in
      body fat.

PMID- 9924270
TI  - Comparison of egg-yolk protein hydrolysate and soyabean protein hydrolysate in
      terms of nitrogen utilization.
AB  - Egg-yolk protein hydrolysate (YPp) is an alternative protein source in formulas
      for infants with intolerance to cow's milk or soyabean protein, or for patients
      with intestinal disorders. However, the nutritional value of YPp has never been
      investigated. YPp was prepared by enzymic hydrolysis of delipidated yolk protein,
      which led to an average peptide length of 2.6 residues. Three experiments were
      performed. In Expt 1, we compared the intestinal absorption rate of YPp and
      soyabean protein hydrolysate (SPp) in rats. YPp and SPp solutions were injected
      into the duodenum of anaesthetized rats and blood samples were taken from the
      portal vein at 7, 15, 30, 60, and 120 min. A higher amino acid concentration in
      the serum of the YPp group demonstrated that YPp was absorbed faster than SPp. In
      Expt 2, the effects of dietary YPp and SPp on body-weight gain, protein
      efficiency ratio (PER) and feed efficiency ratio (FER) were determined. At the
      end of the experiment, body weight had increased in both groups, while PER and
      FER were significantly higher in rats fed on YPp. In Expt 3, to investigate the
      effects of dietary YPp and SPp on N metabolism, we determined the biological
      value and net protein utilization. Yolk protein was the reference protein.
      Biological value and net protein utilization values were very similar between
      animals fed on yolk protein and YPp diets, and significantly higher than in rats
      fed on the SPp diet. The present findings demonstrate that there is no adverse
      effect of hydrolysis of yolk protein on N utilization, and that the nutritive
      value of YPp is similar to that of yolk protein and superior to that of SPp.

PMID- 9924271
TI  - The effects of maternal intake and gestational age on materno-fetal transport of
      vitamin C in the guinea-pig.
AB  - The effects of maternal intake and gestational age on materno-fetal transport of
      vitamin C were investigated in female Dunkin-Hartley guinea-pigs. Twenty-four
      time-mated dams were fed on either a moderate-vitamin C (group A) or a high
      vitamin C (group B) diet, throughout pregnancy. At days 49, 63 and 66 of
      gestation, and at term, three animals from each group were killed and fetuses
      removed by hysterectomy. Plasma, liver, kidney, lungs, heart, placenta and
      amniotic fluid were collected from dams and fetuses and subsequently analysed for
      vitamin C. Fetal plasma and amniotic fluid concentrations showed negative
      associations with gestational age for both dietary groups, independent of an
      effect of dam (P < 0.001). A similar, though not significant, effect of
      gestational age was observed on placental vitamin C and group A fetal tissue
      concentrations. Fetal plasma, placental and amniotic fluid vitamin C
      concentrations were significantly higher in group B than group A (P < 0.001),
      suggesting the influence of maternal diet. Although the level of maternal vitamin
      C intake can influence the circulating concentration in the fetus, there is a
      decrease associated with increasing gestational age, independent of the maternal
      diet. The gestational age-dependent change in the fetal accumulation of vitamin C
      may reflect changes in the rate of placental transfer.

PMID- 9924272
TI  - Molecular biology and nutrition: the quest for integration.

PMID- 9924273
TI  - Regulatory signals in messenger RNA: determinants of nutrient-gene interaction
      and metabolic compartmentation.
AB  - Nutrition has marked influences on gene expression and an understanding of the
      interaction between nutrients and gene expression is important in order to
      provide a basis for determining the nutritional requirements on an individual
      basis. The effects of nutrition can be exerted at many stages between
      transcription of the genetic sequence and production of a functional protein.
      This review focuses on the role of post-transcriptional control, particularly
      mRNA stability, translation and localization, in the interactions of nutrients
      with gene expression. The effects of both macronutrients and micronutrients on
      regulation of gene expression by post-transcriptional mechanisms are presented
      and the post-transcriptional regulation of specific genes of nutritional
      relevance (glucose transporters, transferrin, selenoenzymes, metallothionein,
      lipoproteins) is described in detail. The function of the regulatory signals in
      the untranslated regions of the mRNA is highlighted in relation to control of
      mRNA stability, translation and localization and the importance of these mRNA
      regions to regulation by nutrients is illustrated by reference to specific
      examples. The localization of mRNA by signals in the untranslated regions and its
      function in the spatial organization of protein synthesis is described; the
      potential of such mechanisms to play a key part in nutrient channelling and
      metabolic compartmentation is discussed. It is concluded that nutrients can
      influence gene expression through control of the regulatory signals in these
      untranslated regions and that the post-transcriptional regulation of gene
      expression by these mechanisms may influence nutritional requirements. It is
      emphasized that in studies of nutritional control of gene expression it is
      important not to focus only on regulation through gene promoters but also to
      consider the possibility of post-transcriptional control.

PMID- 9924274
TI  - Effect of breakfast fat content on glucose tolerance and risk factors of
      atherosclerosis and thrombosis.
AB  - Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5.5 g
      fat; L), or a moderately-fatty, (25.7 g fat; M) breakfast of similar energy
      contents for 28 d. Other meals were under less control. An oral glucose tolerance
      test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at
      13.30 hours on day 29. There were no significant treatment differences in fasting
      serum values, either on day 1 or at the termination of treatments on day 29. The
      following was observed on day 29: (1) the M breakfast led to higher OGTT C
      peptide responses and higher areas under the curves (AUC) of OGTT serum glucose
      and insulin responses compared with the OGTT responses to the L breakfast (P <
      0.05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with
      treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59% lower with
      treatment L than with treatment M, between 09.00 and 13.20 hours (P < 0.0001),
      and lower with treatment L than with treatment M during the OGTT (P = 0.005); (4)
      serum triacylglycerol (TAG) concentrations were similar for both treatments,
      especially during the morning, but their origins were different during the
      afternoon OGTT when the Svedberg flotation unit 20-400 lipid fraction was higher
      with treatment L than with treatment M (P = 0.016); plasma apolipoprotein B-48
      level with treatment M was not significantly greater than that with treatment L
      (P = 0.086); (5) plasma tissue plasminogen-activator activity increased after
      breakfast with treatment L (P = 0.0008), but not with treatment M (P = 0.80).
      Waist:hip circumference was positively correlated with serum insulin and glucose
      AUC and with fasting LDL-cholesterol. Waist:hip circumference and serum TAG and
      insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA
      and glucose AUC were correlated. A small difference in fat intake at breakfast
      has a large influence on circulating diurnal NEFA concentration, which it is
      concluded influences adversely glucose tolerance up to 6 h later.

PMID- 9924275
TI  - Resistant starch in the Italian diet.
AB  - Resistant starch (RS) has been defined as the sum of starch and starch
      degradation products that reach the human large intestine (Champ, 1994), and it
      is now regarded as a sub-fraction of starch with a positive impact on colonic
      welfare and lipid metabolism. An early estimate of the RS intake in Europe gave
      an average value of approximately 4 g/d (Dyssler & Hoffem, 1994a). However, since
      no information is available for Italy, the aim of the present study was to
      estimate the intake of RS in the Italian diet by direct analysis of RS in a range
      of typical foods representing the main sources of starch intake in the country.
      The selection of representative foods and of food consumption data were based on
      published results of the National Food Consumption Study conducted during the
      1980s by the National Institute of Nutrition on 10,000 households, using weighed
      food records plus inventory methodologies (Saba et al. 1990; Turrini et al.
      1991). Three main groups of foods were considered: cereals (pasta, rice, bread
      and bread products, and pastries), potatoes, legumes. Different commercial brands
      for each sample were purchased, according to the known presence on the market.
      Samples were prepared 'as eaten' and submitted to simulated chewing, followed by
      total and resistant starch determination using the enzymic procedure published as
      a result of the EC Concerted Action EURESTA (Champ, 1992). From these results,
      the estimated average intake of RS in Italy was found to be 8.5 g/d, with
      regional differences (from 7.2 g/d in the north-west to 9.2 g/d in the south)
      mainly due to the different consumption of some typical Italian starchy food
      (bread, pasta, legumes).

PMID- 9924277
TI  - Absorption of lycopene from single or daily portions of raw and processed tomato.
AB  - To study the relationship between lycopene intake and plasma concentration, ten
      healthy female subjects were given one or more portions of tomato puree or fresh
      raw tomato containing 16.5 mg total lycopene (all-trans + cis forms). In Expt 1
      subjects (n 9) were randomly assigned the single portions of the two tomato
      products and blood samples were collected to follow the change in plasma
      carotenoid concentrations within the first 12 h and on each of the following 5 d
      (104 h). In Expt 2 subjects (n 10) were divided into two groups of five each
      receiving daily dietary portions of tomato puree or fresh raw tomato containing
      16.5 mg total lycopene for 7 d. Fasting blood samples were collected daily. In
      Expt 1 the plasma total lycopene (all-trans + cis forms) concentration, after the
      single portions of tomato puree and raw tomato, varied significantly over time,
      with a first peak reached after 6 h, a further increase after 12 h and a slow
      decrease until 104 h. In Expt 2, when the tomato products were given daily, there
      was a day-by-day increase in the plasma total lycopene concentration, and through
      the following week of a diet without tomato there was a gradual decrease.
      However, values did not return to basal concentrations. Plasma total lycopene
      concentration was higher after the tomato puree intake than after the raw tomato
      in both the first (F(1,8) 7.597; P < 0.025) and the second experiments (F(1,8)
      12.193; P < 0.01) demonstrating a significant effect of food matrix on
      absorption.

PMID- 9924276
TI  - Net energy value of non-starch polysaccharide isolates (sugarbeet fibre and
      commercial inulin) and their impact on nutrient digestive utilization in healthy
      human subjects.
AB  - The energy value of NSP has been expressed as their metabolizable energy (ME)
      content. The aim of the present study was to determine whether differences in ME
      and net energy (NE) contents were similar for insoluble and soluble NSP. Nine
      healthy young men were offered three diets according to a Latin-square design (3
      x 3) with three repetitions: diet C (control), diet B (control + 50 g sugarbeet
      fibre/d) and diet I (control + 50 g commercial inulin/d). After a 16 d adaptation
      period to NSP isolate, food intake was controlled (duplicate meal method) and
      faeces and urine were collected for 8 d. A period of 60 h was devoted to
      measurement of energy expenditure (EE) by whole-body indirect calorimetry. NSP
      isolate ingestion induced significant increases in the number of defecations and
      stool weight resulting from increases in water, DM and microbial mass excretion.
      After deduction of microbial N, differences in faecal N excretion between diets
      were not significantly different. Urinary N excretion was slightly decreased by
      sugarbeet fibre or commercial inulin ingestion but the N balances for the diets
      were not significantly different. Diet energy, N and lipid apparent
      digestibilities decreased by only 1-2%. Commercial inulin was entirely fermented
      and fermentability of sugarbeet fibre averaged 0.886 (SD 0.117). Sugarbeet fibre
      and commercial inulin ME values averaged 10.7 (SD 1.2) and 13.0 (SD 2.3) kJ/g DM
      respectively. NSP-isolate ingestion caused significant (sugarbeet) and
      nonsignificant (inulin) increases in daily EE. The maintenance NE contents of
      sugarbeet fibre and inulin averaged 5.0 (SD 5.0) and 11.9 (SD 1.3) kJ/g DM
      respectively. Differences in maintenance NE contents of NSP isolates were much
      greater than differences in ME values.

PMID- 9924278
TI  - A comparison of the short-term kinetics of zinc metabolism in women during
      fasting and following a breakfast meal.
AB  - The physiological importance and mechanism of the postprandial fall in plasma Zn
      concentration is not well understood. In order to gain further information on
      this apparent redistribution of plasma Zn, a stable isotope, 70Zn, was used to
      study the effect of a breakfast meal on plasma Zn kinetics. Nine women
      participated in two trials, a fasting trial and a breakfast-meal trial; five of
      the women participated in a third trial in which the energy content of the
      breakfast meal was doubled. At each trial, 0.1 mg of 70Zn was infused
      intravenously, and the plasma disappearance of the isotope was analysed using a
      two-compartment model of Zn kinetics. Plasma Zn concentration fell significantly
      following the two trials in which the subjects were given meals, reaching low
      points that were 13 and 19%, respectively, below concentrations at comparable
      times during the fasting trial. Kinetic analysis revealed that after the doubled
      breakfast meal there was a significant fall (P < 0.007) in the size of the most
      rapidly turning over Zn pool (pool (a)) from 2.90 (SE 0.13) mg in the fasting
      state to 2.47 (SE 0.14) mg postprandially. The fractional turnover rate of pool
      (a) to other extravascular Zn pools, i.e. outside the two-compartment system, was
      also significantly elevated after the doubled breakfast meal (P < 0.05). These
      results suggest that the decline in plasma Zn concentration following a meal is
      due to a redistribution of Zn from the plasma to other more slowly turning over
      extravascular pools that may be involved in the assimilation and metabolism of
      fuels following food intake.

PMID- 9924279
TI  - Transfers of N metabolites across the ovine liver in response to short-term
      infusions of an amino acid mixture into the mesenteric vein.
AB  - The effect of acute (4.5 h) infusions into the mesenteric vein of an amino acid
      (AA) mixture, which simulated the composition of rumen microbial protein, on net
      transfers of NH3, urea and total AA across the portal-drained viscera (PDV) and
      liver in the ovine has been examined. Four wether sheep were surgically prepared
      with vascular catheters across the PDV and liver (Lobley et al. 1995) and were
      offered a basal diet of 1000 g grass pellets/d (approximately 1.4 x energy
      maintenance). Each animal was infused at weekly intervals with one of four
      dilutions of the AA mixture. These dilutions provided 0.44, 0.88, 1.32 and 1.84
      mmol AA-N/min infused, the lowest of which approximately doubled the net
      absorption of AA-N from the basal diet. Animals were treated with heparin to
      allow continuous collection of blood by peristaltic pump for 2 h preceding, and
      between 0.5-2.5 and 2.5-4.5 h after, the start of the AA infusions. Blood flow in
      the hepatic artery increased (100 v. 208 g/min; P = 0.002) in response to AA
      infusion, while hepatic portal venous flow decreased (2090 v. 1854 g/min; P =
      0.006). The AA infusion also stimulated O2 uptake by the PDV (P < 0.001) and
      liver (P = 0.016). Absorption across the PDV and hepatic removal of NH3 were
      unchanged between basal and amino acid infusion conditions. Urea-N removal across
      the PDV was unaltered, but hepatic production increased (P < 0.001) with level of
      AA infusion. During infusions, net appearance of AA across the PDV was below the
      theoretical level. This may have been due to inhibition of AA uptake from the
      small intestine, and/or increased removal by the digestive tract of AA from the
      systemic circulation associated with greater arterial concentrations. Hepatic
      extraction of AA increased with level of infusion, both for total AA and those
      included in the infusate. Total hepatic urea-N production tended towards a
      maximum (estimated as 2 mumol N/g liver wet weight per min). The AA removed by
      the liver and not used for ureagenesis remained similar (170 mumol AA-N/min)
      between basal and AA infusions. This was presumed available for anabolic purposes
      (mainly synthesis of export proteins). The proportion of net AA-N appearance
      (absorption plus infused) across the PDV removed by the liver declined from 0.71
      to 0.53 between basal and AA infusions. In contrast to findings from cattle (Wray
      Cahen et al. 1997), increased AA infusion did not alter the net removal of
      glutamine across the liver. This may reflect differences between the studies in
      NH3: AA-N absorbed. Further differences between the cattle study and the current
      findings may relate to the different physiological state (pregnancy v. growth),
      which may alter the partition of AA between anabolic and catabolic fates.

PMID- 9924280
TI  - Passage through the rumen and the large intestine of sheep estimated from faecal
      marker excretion curves and slaughter trials.
AB  - External digesta markers (Yb-labelled diets and Co-EDTA) were given orally as a
      pulse dose to four pairs of Rasa Aragonesa twin ewe lambs, fed on either chopped
      or ground and pelleted lucerne hay, in order to estimate slow (k1) and fast (k2)
      rates of passage of liquid and solid phase from faecal marker excretion curves.
      After the faecal sampling period daily doses of the same markers were infused
      continuously for 5 d and the animals slaughtered. Concentrations of markers in
      the different compartments of the gut were determined and used to calculate mean
      retention times. The results showed that the rumen and the large intestine were
      the two main mixing compartments of the gut, accounting for more than 95% of
      total mean retention time. Rates of passage estimated from faecal marker
      excretion did not accurately represent marker kinetics in the compartments of the
      gut derived from slaughter data. Accuracy in the estimation of fractional outflow
      rate from rumen (kR) by k1 was higher for low values of kR whereas k2
      consistently overestimated large intestine outflow rate (kLI), especially for
      high values of kR. The relationship between outflow rates from the main two
      mixing compartments was important in influencing the accuracy of prediction of
      faecal estimates.

PMID- 9924281
TI  - Effects of L-carnitine supplementation of diets differing in energy levels on
      performance, abdominal fat content, and yield and composition of edible meat of
      broilers.
AB  - Responses to supplemental dietary L-carnitine of broilers fed on diets with
      different levels of metabolizable energy (ME) were investigated using growth
      performance and some carcass measurements. Three isonitrogenous diets containing
      13.5, 12.8 or 12.2 MJ ME/kg were formulated, with or without supplemental L
      carnitine (50 mg/kg) and fed ad libitum from 18 to 53 d of age. Supplemental L
      carnitine increased body-weight gain (BWG) and improved feed conversion (FC)
      during the first 2 weeks of study. FC was also improved during the fourth week of
      the experiment. Weights of breast yield and thigh meat yield were significantly
      increased, whereas quantity and percentage of abdominal fat were reduced by
      supplemental L-carnitine. A significant interaction between supplemental dietary
      L-carnitine and dietary energy level was noted for BWG and FC during the second
      week of study.

PMID- 9924283
TI  - Pre- and probiotics: where are we today? Introduction.

PMID- 9924282
TI  - Vitamin A deficiency induces morphometric changes and decreased functionality in
      chicken small intestine.
AB  - The effect of vitamin A on chicken intestinal mucosal morphology and
      functionality was tested in relation to severe and mild vitamin A deficiency and
      vitamin A repletion. Compared with rats and mice, chickens have a very quick
      response to a deficient dietary intake. Severe vitamin A deficiency altered the
      small intestine of chickens at both the biochemical and the morphological levels.
      It caused the loss of mucosal protein, reduced villus height and crypt depth and
      diminished activities of disaccharidases, transpeptidase and alkaline phosphate
      (EC 3.1.3.1). The ratios RNA:DNA, RNA:protein and protein:DNA, and the DNA
      concentrations in 1 g intestinal tissue, together with morphological
      measurements, provided knowledge about the pattern of lesion. The results
      indicated that (1) lack of vitamin A influenced cellular hyperplasia as it caused
      an increase in DNA content and in the number of enterocytes per villus; (2) lack
      of vitamin A influenced cellular hypertrophy as it decreased the protein:DNA
      ratio. There was no difference in mucosal enzyme activity between the two
      deficient groups. The repletion group exhibited a remarkable increase in mucosal
      enzyme activity only 4 d after switching to the control diet. The evidence
      presented in our paper suggests that the low vitamin A supply interferes with the
      normal activity of chicken intestinal mucosa as it influences the processes of
      proliferation and maturation of enterocytes.

PMID- 9924284
TI  - Prebiotics and synbiotics: concepts and nutritional properties.
AB  - The main role of diet is to provide enough nutrients to meet the requirements of
      a balanced diet, while giving the consumer a feeling of satisfaction and well
      being. The most recent knowledge in bioscience supports the hypothesis that diet
      also controls and modulates various functions in the body, and, in doing so,
      contributes to the state of good health necessary to reduce the risk of some
      diseases. It is such an hypothesis which is at the origin both of the concept of
      'functional food' and the development of a new scientific discipline of
      'functional food science'. In the context of this paper the potential 'functional
      foods' to be discussed are the prebiotics and the synbiotics. The prebiotics
      developed so far are the non-digestible oligosaccharides and especially the non
      digestible fructans among which chicory fructans play a major role. The chicory
      fructans are beta (2-1) fructo-oligosaccharides classified as natural food
      ingredients. They positively affect various physiological functions in such a way
      that they are already or may, in the future, be classified as functional food
      ingredients for which claims of functional effects or of disease risk reduction
      might become authorized. They are classified as prebiotic and have been shown to
      induce an increase in the number of bifidobacteria in human faecal flora. As part
      of a synbiotic-type product, they are already bifidogenic at a dose of 2.75 g/d
      and the effect lasts for at least 7 weeks. The other potential functional effects
      are on the bioavailability of minerals, but also, and more systemically, on the
      metabolism of lipids. Potential health benefits may concern reduction of the risk
      of intestinal infectious diseases, cardiovascular disease, non-insulin-dependent
      diabetes, obesity, osteoporosis and cancer. However, except for the prebiotic
      effect, and tentatively the improvement of calcium bioavailability, the evidence
      to support such effects is still missing in humans though hypotheses already
      exist to justify nutrition studies.

PMID- 9924285
TI  - Health benefits of probiotics.
AB  - This paper reviews the evidence for the claims of health benefits derived from
      the use of probiotics. A brief history of probiotics and the types of probiotics
      currently used and the criteria for the selection of probiotics is discussed. The
      ability of probiotics to enhance the nutritional content and bioavailability of
      nutrients and the scientific evidence for the usefulness of probiotics in
      alleviating the symptoms of lactose intolerance and in enhancing growth
      development is examined. The remainder of the review focuses on studies of a
      specific probiotic, Lactobacillus GG which has been extensively investigated for
      its health benefits in humans and animals. These studies severe as a model for
      the potential benefits of probiotics. The ability of Lactobacillus GG to treat or
      prevent diarrhoeal disease, to serve as an adjuvant for vaccines, to prevent
      rotavirus-induced diarrhoea, to prevent milk-based allergic reactions, alcohol
      induced liver disease and colon cancer are presented. The review concludes with a
      discussion of the data supporting the safety of probiotics.

PMID- 9924286
TI  - Dietary modulation of the human gut microflora using prebiotics.
AB  - The human colonic flora has both beneficial and pathogenic potentials with
      respect to host health. There is now much interest in manipulation of the
      microbiota composition in order to improve the potentially beneficial aspects.
      The prebiotic approach dictates that non-viable food components are specifically
      fermented in the colon by indigenous bacteria thought to be of positive value,
      e.g. bifidobacteria, lactobacilli. Any food ingredient that enters the large
      intestine is a candidate prebiotic. However, to be effective, selectivity of the
      fermentation is essential. Most current attention and success has been derived
      using non-digestible oligosaccharides. Types primarily being looked at include
      those which contain fructose, xylose, soya, galactose, glucose and mannose. In
      particular, fructose-containing oligosaccharides, which occur naturally in a
      variety of plants such as onion, asparagus, chicory, banana and artichoke, fulfil
      the prebiotic criteria. Various data have shown that fructo-oligosaccharides
      (FOS) are specifically fermented by bifidobacteria. During controlled feeding
      studies, ingestion of these prebiotics causes bifidobacteria to become
      numerically dominant in faeces. Recent studies have indicated that a FOS dose of
      4 g/d is prebiotic. To exploit this concept more fully, there is a need for
      assessments of (a) improved determination of the gut microbiota composition and
      activity; (b) the use of molecular methodologies to assess accurately prebiotic
      identities and develop efficient bacterial probing strategies; (c) the prebiotic
      potential of raw and processed foods; and (d) the health consequences of dietary
      modulation.

PMID- 9924287
TI  - Development of consumer probiotics for the US market.
AB  - Curiosity about probiotic bacteria is high. This is not surprising given the
      rapid growth of the natural products market in the USA, which was 22% in 1995
      (New Hope Natural Media, Boulder, CO). Although probiotic cultures are only one
      component of that market, this trend shows that consumers in the USA are
      increasingly taking a pro-active stance towards their health and are purchasing
      products not only to eliminate what is perceived as dietary negatives but to
      increase the levels of dietary positives (Wrick, 1995). This shift in consumer
      attitude bodes well for the development of the American probiotic market. This
      article describes the composition, promotion and labelling of probiotic
      containing products, discusses attributes of commercial probiotic bacteria, and
      estimates the size of the probiotic market in the USA. This market information
      was obtained from several published (Anon, 1996a,b) and unpublished but
      commercially available (SPINS Information Services, San Francisco, CA and New
      Hope Natural Media, Boulder, CO) sources.

PMID- 9924288
TI  - Prevention of colon cancer by pre- and probiotics: evidence from laboratory
      studies.
AB  - Oligofructose and inulin, selective fermentable chicory fructans, have been shown
      to stimulate the growth of bifidobacteria which are regarded as beneficial
      strains in the colon. Studies were designed to evaluate inulin (Raftiline) and
      oligofructose (Raftilose), for their potential inhibitory properties against
      aberrant crypt foci (ACF) formation in the colon of rats. ACF are putative
      preneoplastic lesions from which adenomas and carcinomas may develop. The results
      of this study demonstrate that dietary administration of oligofructose and inulin
      inhibits the formation of preneoplastic lesions in the colon suggesting the
      potential colon tumour inhibitory properties of chicory fructans. Since these
      prebiotics selectively stimulate the growth of bifidobacteria, tumour inhibitory
      activity of lyophilized cultures of Bifidobacterium longum (BL) against
      azoxymethane (AOM)-induced colon carcinogenesis in rats and modulating effect of
      these cultures on colonic tumour cell proliferation, ornithine decarboxylase
      (ODC) activity, and ras-p21 oncoprotein expression were investigated. Dietary
      administration of lyophilized cultures of BL strongly suppressed AOM-induced
      colon tumour development. Inhibition of colon carcinogenesis was associated with
      a decrease in colonic mucosal cell proliferation and colonic mucosal and tumour
      ODC and ras-p21 activities.

PMID- 9924289
TI  - Effects of probiotics and prebiotics on blood lipids.
AB  - Since the early work of Mann and Spoerry, probiotics in the form of fermented
      milk products have been reputed to have cholesterol-lowering properties in
      humans. However, studies conducted since the early 1970s have produced equivocal
      findings, with interpretation of the outcomes complicated by use of excessive
      quantities of product, inadequate sample sizes, failure to control nutrient
      intake and energy expenditure and variations in baseline blood lipids. More
      recent studies are of better quality, but fail to provide convincing evidence
      that 'live' fermented milk products have cholesterol-lowering efficacy in man.
      Future studies using probiotics should ensure adequate sample sizes sufficient to
      detect relatively small changes in blood cholesterol and should be conducted over
      longer periods of time. The recent introduction of the concept of prebiotics has
      directed attention towards the possibility that alterations in gut microflora
      induced by the fermentation of non-digestible components of the diet may also
      have the potential to influence systemic lipid metabolism. This possibility has
      been strengthened by the observation that in animals, dietary
      oligofructosaccharides cause suppression of hepatic triglyceride and VLDL
      synthesis, resulting in marked reductions in triglyceride, and to a lesser extent
      cholesterol, levels. Evidence for similar effects in humans is sparse and more
      studies are needed, particularly with respect to effects on postprandial
      triglyceride concentrations.

PMID- 9924290
TI  - European market developments in prebiotic- and probiotic-containing foodstuffs.
AB  - A growing number of food manufacturers in western Europe are beginning to explore
      the commercial opportunities for foodstuffs containing health-promoting microbial
      food supplements (probiotics) and health-promoting non-digestible food
      ingredients (prebiotics). A prebiotic is considered to affect the host
      beneficially by selectively stimulating the growth and/or activity of one or a
      limited number of naturally present or introduced bacterial species in the colon,
      also leading to a claimed improvement in host health. Increasingly, probiotics
      and prebiotics are used in combination, this being termed a synbiotic (Gibson &
      Roberfroid, 1995). Throughout European history, fermented milk products in
      particular have been considered beneficial to health, but only in recent years
      has there been scientific support for these beliefs. Issues considered important
      to the continuing development of this growing market are proof of safety, proof
      of efficacy, consumer education, market positioning, price and appropriate health
      claims strategies. Until recently, much of the innovation in the use of
      probiotics and prebiotics has been in the dairy cabinet, with an ever-growing
      number and range of 'health-promoting' yoghurts and yoghurt-type fermented milk
      being made available to the European consumer, a market which is currently
      estimated to be worth in excess of $US2 billion per annum (Hilliam et al. 1997).
      However, prebiotics are beginning to find increasing application outside the
      dairy sector, particularly in baked goods. A key driver behind the broadening
      application of prebiotics has been the pro-active stance taken by key prebiotic
      suppliers such as Beghin-Say, Orafti and Cosucra. To date, market activity in
      probiotic- and prebiotic-containing foods has centred around three health
      propositions, namely improving general gut health, lowering blood cholesterol and
      improving the body's natural defences.

PMID- 9924291
TI  - Responding to the challenge of clinical practice variations.

PMID- 9924292
TI  - Lens cell growth and posterior capsule opacification: in vivo and in vitro
      observations.

PMID- 9924293
TI  - Terminology of sub-RPE deposits: do we all speak the same language?

PMID- 9924294
TI  - Variation in indications for cataract surgery in the United States, Denmark,
      Canada, and Spain: results from the International Cataract Surgery Outcomes
      Study.
AB  - BACKGROUND/AIMS: International comparisons of clinical practice may help in
      assessing the magnitude and possible causes of variation in cross national
      healthcare utilisation. With this aim, the indications for cataract surgery in
      the United States, Denmark, the province of Manitoba (Canada), and the city of
      Barcelona (Spain) were compared. METHODS: In a prospective multicentre study,
      patients scheduled for first eye cataract surgery and aged 50 years or older were
      enrolled consecutively. From the United States 766 patients were enrolled; from
      Denmark 291; from Manitoba 152; and from Barcelona 200. Indication for surgery
      was measured as preoperative visual status of patients enlisted for cataract
      surgery. Main variables were preoperative visual acuity in operative eye, the VF
      14 score (an index of functional impairment in patients with cataract) and ocular
      comorbidity. RESULTS: Mean visual acuity were 0.23 (USA), 0.17 (Denmark), 0.15
      (Manitoba), and 0.07 (Barcelona) (p < 0.001). When restricting the sample to eyes
      with normal retina and macula, no significant difference between United States
      and Denmark was observed (p > 0.05). Mean VF-14 scores were 76 (USA), 76
      (Denmark), 71 (Manitoba), and 64 (Barcelona) (p < 0.001). CONCLUSION: Similar
      indications for cataract surgery were found in the United States and Denmark.
      Significantly more restricted indications were observed in Manitoba and
      Barcelona. Possible explanations for the results are discussed, including
      differences in sociodemographic characteristics, access to care, surgeons'
      willingness to operate, and patient demand.

PMID- 9924295
TI  - Laser scanning tomography of localised nerve fibre layer defects.
AB  - AIMS: Retinal nerve fibre layer photography is a well established method to
      qualitatively document early structural changes which might be induced by primary
      open angle glaucoma. The aim was to analyse localised retinal nerve fibre layer
      (RNFL) defects in a new quantitative way with respect to surface topography,
      defect width, and surface reflectivity by means of the technique of confocal
      scanning laser tomography. METHODS: 12 eyes of 12 patients with a localised RNFL
      defect documented in RNFL photographs and a normal appearance of the optic disc
      were enrolled in the study. Using confocal laser scanning tomography (Heidelberg
      retina tomograph, HRT) a series of 32 optical section images from different focal
      planes of the retina at the site of the RNFL defects were obtained. The optical
      section images, the reflectivity images, and the topographic images were analysed
      regarding the visibility of the RNFL defects. The mean surface height and the
      reflectance at the sites of the RNFL damage were measured and compared with the
      adjacent apparently normal retina. The width of the RNFL defect at 1 mm distance
      from the disc border was evaluated. RESULTS: RNFL defects could be detected in
      nine of 12 reflectivity images (75%). Single optical section images displayed the
      RNFL defects in 12 of 12 eyes. The defect width ranged from 0.11 to 1.0 mm. In
      six of 12 eyes a surface depression (34 (SD 5) microns; range 21-47 microns) was
      present. The reflectance ratio ranged from 0.68 to 0.94 at the site of the RNFL
      defect. In eyes with a glaucomatous scotoma in a 6 degrees grid visual field
      (VF), the defect width was at least 0.25 mm. Surface depression and low
      reflectance ratio were found irrespective of the presence of a scotoma in the 6
      degrees grid VF. CONCLUSION: The majority of localised RNFL defects can be
      detected in reflectivity images from laser scanning tomograms. Localised RNFL
      defects may be differentiated according to surface topography into those with and
      those without a measurable surface depression. A small but deep RNFL defect is
      not necessarily associated with a scotoma in routine 6 degrees grid VF static
      perimetry.

PMID- 9924297
TI  - Does raised intraocular pressure begin in utero?
AB  - AIM: To determine whether fetal and infant growth, as assessed by weight at birth
      and weight at 1 year, are related to intraocular pressure. METHODS: 717 men and
      women born in Hertfordshire between 1920 and 1930, for whom records of birth
      weight and weight at 1 year were available, were examined. Visual fields were
      assessed using the Takagi central 25 degrees 75 point static threshold screening
      program. Tonometry was performed using the Perkin's tonometer. The disc was
      assessed by direct ophthalmoscopy through dilated pupils. RESULTS: A significant
      inverse relation was found between systolic blood pressure and birth weight.
      However, no association was found between birth weight or weight at 1 year and
      intraocular pressure, cup/disc ratio, or visual field defects. CONCLUSIONS: There
      was no evidence to support fetal or infant growth as being important factors for
      the subsequent development of raised intraocular pressure.

PMID- 9924296
TI  - Vertical cup/disc ratio in relation to optic disc size: its value in the
      assessment of the glaucoma suspect.
AB  - AIMS: The vertical cup/disc ratio (CDR) has long been used in the assessment of
      the glaucoma suspect, though the wide range of CDR values in the normal
      population limits its use. Cup size is related physiologically to disc size and
      pathologically to glaucomatous damage. Disc size can be measured at the slit lamp
      as the vertical disc diameter (DD). The ability of the CDR, in relation to DD, to
      identify glaucomatous optic discs was investigated. METHODS: 88 normal, 53 early
      glaucoma, and 59 ocular hypertensive subjects underwent stereoscopic optic disc
      photography and clinical biometry. Photographs were analysed in a masked fashion
      by computer assisted planimetry. The relation between vertical cup diameter and
      DD was explored by linear regression, and expressed in terms of CDR. The upper
      limit of normal was defined by the 95% prediction intervals of this regression
      (method 1) and by the upper 97.5 percentile for CDR (method 2). The sensitivity
      and specificity of CDR to identify an optic disc as glaucomatous was tested with
      these disc size dependent and disc size independent cut offs in small, medium,
      and large discs. RESULTS: The CDR was related to DD by the equation CDR = (-1.31
      + (1.194 x DD))/DD. The sensitivity in small, medium, and large discs was 80%,
      60%, and 38% respectively for method 1 and 33%, 67%, and 63% respectively for
      method 2. Specificity was 98.9% (method 1) and 97.7% (method 2). CONCLUSIONS: The
      CDR, relative to disc size, is useful clinically, especially to assist in
      identifying small glaucomatous discs.

PMID- 9924298
TI  - Ocular contact time of a carbomer gel (GelTears) in humans.
AB  - BACKGROUND/AIMS: Carbomers are widely used in products for the treatment of dry
      eye; however, the polymer gel thins on addition of probes (for example,
      fluorescein salt) confounding the comparison of products by objective clinical
      tests such as spectrophotofluorimetry or scintigraphy. A novel method of
      radiolabelling carbomer gels, with minimum change to their rheology, has
      permitted the non-invasive evaluation of precorneal residence of the gel in
      volunteers using gamma scintigraphy. The technique was used to evaluate the
      precorneal clearance of the liquid phase and of a suspended particulate in
      GelTears. METHODS: Low sodium technetium-99m labelled
      diethylenetriaminepentacetic acid (99mTc-DTPA) was used to label carbomer 940
      gel, either adsorbed onto sterile charcoal to model an entrapped drug, or added
      directly to the gel to a final activity of 1 MBq per 25 microliters dose. The
      clearance of the labelled gels was then compared with 99mTc-DTPA labelled saline
      in 12 volunteers. RESULTS: The addition of the low sodium radiopharmaceutical
      produced insignificant rheological changes in the gel compared with conventional
      99mTc-DTPA labelling. The residence times on the eye of the gel formulations were
      significantly greater than that of the saline control. At 8 minutes postdosing,
      the label levels retained (mean (SD)) on the ocular surface were: saline, 7%
      (7%); 99mTc-DTPA gel, 42% (27%); and 99mTc-carbon gel, 42% (20%) of administered
      dose. There was no difference observed in the precorneal distribution between
      99mTc-DTPA solution and particulate markers. CONCLUSIONS: These data demonstrate
      that carbomer based gels significantly extend contact of solutes or suspended
      solids with the corneal surface. The method of labelling does not significantly
      change the initial viscosity and is superior to previous methods which have used
      sodium salts (for example, sodium fluorescein) and therefore underestimate
      contact time.

PMID- 9924300
TI  - Conjunctival impression cytology for vitamin A deficiency in the presence of
      infectious trachoma.
AB  - BACKGROUND/AIMS: Increased morbidity and mortality from a number of infectious
      diseases have been associated with vitamin A deficiency. Trachoma and vitamin A
      deficiency are both important causes of blindness in Nepal. The purpose of this
      study was to determine the association between the diagnosis of vitamin A
      deficiency by conjunctival impression cytology and the diagnosis of infectious
      trachoma by the polymerase chain reaction (PCR) in the Lumbini zone of Nepal.
      METHODS: 70 children under the age of 11 in a rural village in the Lumbini zone
      were examined for clinical evidence of active trachoma. The conjunctiva of each
      child was tested for ocular Chlamydia trachomatis infection using PCR, and for
      loss of goblet cells (a sign of subclinical vitamin A deficiency) using
      conjunctival impression cytology. RESULTS: The presence of infectious trachoma
      was associated with the loss of goblet cells on conjunctival impression cytology
      (p = 0.02). This relation was present and significant even when adjusted for age
      (p = 0.05) and degree of inflammation (p = 0.02). In fact, even subclinical
      infection with chlamydia was associated with an abnormal conjunctival impression
      cytology (p = 0.02). CONCLUSIONS: Children with infectious trachoma are
      significantly more likely to have an abnormal conjunctival impression cytology,
      even if the infection is subclinical. Thus, the diagnosis of vitamin A deficiency
      from conjunctival impression cytology alone should be made with some caution in
      areas with endemic trachoma. Further studies will be needed to determine the
      cause of this association.

PMID- 9924299
TI  - Treatment of common ocular allergic disorders; a comparison of lodoxamide and
      NAAGA.
AB  - BACKGROUND/AIMS: Lodoxamide tromethamine and N-acetyl-aspartyl glutamic acid
      (NAAGA) are mast cell stabilisers, both of which have been shown to be effective
      in the treatment of allergic conjunctivitis. The aim of this study was to compare
      the two compounds in patients with common ocular allergic disorders. METHODS: 73
      patients participated in a double masked, randomised multicentre study. Diagnoses
      were chronic allergic conjunctivitis, vernal conjunctivitis, seasonal and atopic
      conjunctivitis. 36 patients were treated with lodoxamide 0.1% and 37 with NAAGA
      4.9%, the drops being instilled four times daily for up to 56 days. RESULTS: The
      overall opinion of the physicians and the patients was in favour of lodoxamide at
      day 10 of the study. At this time, 86% of lodoxamide treated and 49% of NAAGA
      treated patients considered they had improved. The patients' opinion favoured
      lodoxamide at day 28 and both physicians' and patients' evaluations were in
      favour of lodoxamide at day 42. Evaluation of signs and symptoms indicated
      superiority of lodoxamide at days 42 and 56. Both treatments were well tolerated.
      CONCLUSION: While both lodoxamide and NAAGA treatments are associated with
      clinical improvements in patients with allergic conjunctivitis, lodoxamide may
      have an earlier onset of action.

PMID- 9924301
TI  - Correlation between surface water contamination with amoeba and the onset of
      symptoms and diagnosis of amoeba-like keratitis.
AB  - AIM: A seasonal variation was noted in the incidence of amoeba-like keratitis in
      Iowa. The level of contamination of amoeba in surface water has been found
      previously to vary on a monthly basis for Tulsa, Oklahoma, a region with a
      similar climate. It was hypothesised that this seasonal variation in amoeba-like
      keratitis correlated with the concentration of amoeba in surface water. METHODS:
      The monthly variation in the onset of symptoms was determined and date of
      diagnosis in 137 cases of amoeba-like keratitis, in Iowa, from January 1993 to
      the end of December 1996. RESULTS: Over a 4 year period a significant variation
      was found, on a monthly basis, in the onset of symptoms as reported by the
      patient. There were two peak periods per year when the onset of symptoms was most
      frequent: June and November. This corresponded closely with the concentration of
      amoeba in the ground water reported for a similar region in the mid-west (Tulsa,
      Oklahoma). A yearly increase was found in the number of cases diagnosed from
      January 1993 to the end of December 1996. CONCLUSIONS: This study supports the
      hypothesis that the concentration of amoeba in surface water may influence the
      rate of an amoeba-like keratitis infection.

PMID- 9924302
TI  - Internal resection of posterior uveal melanomas.
AB  - AIMS: To evaluate the safety and efficacy of internal resection in the treatment
      of malignant melanoma of the choroid. METHODS: 32 consecutive patients with
      histopathologically proved malignant choroidal melanomas were treated with
      internal resection. 29 of the 32 (90.6%) tumours were within 2 disc diameters of
      the optic nerve or fovea. The surgery was performed at two university centres by
      one of the authors. Follow up was between 1 and 85 months (mean 40.1 months).
      RESULTS: Three patients developed distant metastases and died of malignant
      melanoma (metastatic and mortality rate 9.4%). In one case, distant metastases
      developed in association with an intraocular recurrence. There have been no other
      intraocular recurrences. The most common postoperative complication was vitreous
      haemorrhage, which occurred in 12 patients (37.5%); cataract occurred in eight
      eyes; and three patients developed retinal detachment postoperatively. Three of
      the operated eyes have been enucleated (9.4%); a total of four (12.5%) have lost
      light perception. 10 patients (31.2%) had visual acuities of 6/60 or better and
      18 of 32 (56.3%) were between 6/120 and light perception. CONCLUSION: These data
      suggest that the internal resection of posterior uveal melanomas is a reasonable
      globe saving management option. This treatment modality is particularly well
      suited to elevated tumours in close proximity to the optic nerve or fovea.

PMID- 9924304
TI  - Frequency of asymptomatic choroidal metastasis in patients with disseminated
      breast cancer: results of a prospective screening programme.
AB  - AIM: To determine the frequency of visually asymptomatic choroidal metastasis in
      patients with disseminated breast cancer and its dependence on the incidence of
      metastasis by number and site of other organ metastases. METHODS: From January
      1995 until April 1997 120 patients irradiated for disseminated breast cancer
      underwent ophthalmological screening for choroidal metastasis. No patient was
      symptomatic for ocular disease. 68 out of 120 patients were found to have
      metastases in one organ and 52 patients had metastases in more than one organ.
      80% of the patients had bone metastases, 25% lung metastases, 22% liver
      metastases, 15% brain metastases, and 22% had metastases in other organs.
      RESULTS: Six patients (5%) were found to have asymptomatic choroidal metastases.
      Five patients had unilateral and one patient bilateral metastases. 52 patients
      with more than one involved organ had a significantly higher risk for
      asymptomatic choroidal metastasis (6/52, 11%) than 68 patients with metastases in
      only one organ (0/68) (p = 0.006). In univariate analysis a significantly higher
      risk was seen for patients with lung metastases (14% choroidal metastases versus
      2% in patients without lung metastases, p = 0.03) and for patients with brain
      metastases (17% choroidal metastases versus 3% in those without brain metastases,
      p = 0.04). CONCLUSION: In disseminated breast cancer the incidence of
      asymptomatic choroidal metastases was 5% and increased to 11% when more than one
      organ was involved in metastatic spread. Risk factors for choroidal metastases
      were dissemination of disease in more than one organ and the presence of lung and
      brain metastases.

PMID- 9924303
TI  - Role of chemotherapy alone or in combination with hyperthermia in the primary
      treatment of intraocular retinoblastoma: preliminary results.
AB  - BACKGROUND: The efficacy of the etoposide-carboplatin combination in extraocular
      retinoblastoma is well known. This drug combination is therefore used in
      intraocular retinoblastoma, as primary reduction chemotherapy, before local
      treatment. The use of carboplatin in combination with diode laser hyperthermia as
      local treatment (thermochemotherapy) has been recently described as a
      conservative approach avoiding external beam radiotherapy in posterior pole
      tumours. METHODS: All patients were reviewed, who were treated for retinoblastoma
      at the Institut Curie between June 1994 and October 1995, in whom treatment
      included either reduction chemotherapy or thermochemotherapy or both modalities
      successively. 23 patients presenting with unilateral (three) or bilateral (20)
      intraocular retinoblastoma received neoadjuvant chemotherapy consisting of two
      courses of etoposide 150 mg/m2/day and carboplatin 200 mg/m2/day for 3 days. 15
      patients (17 eyes), eight of whom had already received neoadjuvant chemotherapy,
      were treated by thermochemotherapy. RESULTS: Neoadjuvant chemotherapy: overall,
      seven eyes in seven patients could be treated conservatively, avoiding external
      beam irradiation, with a median follow up of 14 months. Thermochemotherapy:
      external beam irradiation was avoided for 14 of the 17 eyes treated. CONCLUSION:
      Integration of neoadjuvant chemotherapy and combined treatment with carboplatin
      and diode laser, into the therapeutic armamentarium for retinoblastoma allows use
      of more aggressive treatments such as enucleation and external beam radiation.

PMID- 9924305
TI  - Phenotype of a British North Carolina macular dystrophy family linked to
      chromosome 6q.
AB  - AIMS: To document the phenotype of an autosomal dominant macular dystrophy
      diagnosed as having North Carolina macular dystrophy (NCMD) in this British
      family, and to verify that the disease locus corresponds with that of MCDR1 on
      chromosome 6q. METHODS: 37 family members were examined and the phenotype
      characterised. DNA samples from the affected members, 19 unaffected and five
      spouses, were used to perform linkage analysis with six microsatellite marker
      loci situated within the MCDR1 region of chromosome 6q. RESULTS: Every affected
      family member had lesions characteristic of NCMD, which developed early in life
      and usually remain stable thereafter. Although fundus changes are evident in the
      periphery, all tests revealed that functional loss is restricted to the macula.
      Some patients with large macular lesions had good visual acuity with fixation at
      the edge of the lesion at 5 degrees eccentricity. Significant linkage to the
      MCDR1 locus on chromosome 6q was obtained with three marker loci, with a maximum
      lod score of 5.9 (q = 0.00) obtained with D6S249. CONCLUSION: This family has the
      typical phenotype NCMD, and the causative gene was linked to the disease locus
      (MCDR1) on chromosome 6q. Early onset and localisation of the disease to the
      central macula allow specialisation of eccentric retina in some eyes with
      resultant good visual acuity.

PMID- 9924306
TI  - Prophylactic laser treatment in early age related maculopathy reduced the
      incidence of exudative complications.
AB  - AIM: To investigate the effect of prophylactic laser treatment on drusen area and
      incidence of exudative lesions in patients with soft drusen maculopathy. METHODS:
      In a prospective study, patients with early age related maculopathy (ARM) and
      good visual acuity were randomized to laser treatment or to a control group. Each
      group consisted of two subgroups: a fellow eye group and a bilateral drusen
      group. At 3 years, 36 of 38 enrolled patients remained in the study.
      Photocoagulation was performed with an argon green laser, approximately 100 mild
      laser burns being placed on and between the drusen in a perifoveal temporal
      horseshoe-shaped area. Both cases and controls were subjected to fundus colour
      photographs and fluorescein angiograms at regular intervals, and the drusen area
      was calculated in both photographs and angiograms. At baseline, there were no
      significant differences (p > 0.3-0.8) in drusen area between the groups. RESULTS:
      In the treatment group, mean drusen area decreased significantly in the fundus
      photographs as well as in the angiograms (p < 0.001). Visual acuity and colour
      contrast sensitivity (CCS) did not change significantly. All these results are
      valid also for the subgroups. In the control group, however, mean drusen area
      increased significantly (p < 0.001). Mean visual acuity decreased significantly
      (p < 0.01) as did the colour contrast sensitivity along the tritan axis (p =
      0.02). For the fellow eye control group (n = 7), the increase in drusen area in
      fundus photographs and the decrease in CCS along the tritan axis were not
      statistically significant (p = 0.57 and p = 0.37, respectively). Furthermore, at
      3 years, five patients in the control group showed exudative lesions (1/7 in the
      fellow eye group and 4/12 in the bilateral drusen group), whereas no such
      complications occurred in the treatment group. One patient developed a small
      atrophy, however. Thus, there is now a significant difference (p = 0.047),
      however with a large 95% confidence interval, 0.06-0.46, regarding exudative
      complications between the treated group and the control group in our small
      patient material. CONCLUSION: Perifoveal mild laser treatment causes a reduction
      in drusen area in patients with soft drusen maculopathy and may lower the
      incidence of exudative lesions.

PMID- 9924307
TI  - Videofunduscopy and videoangiography using the scanning laser ophthalmoscope in
      Vogt-Koyanagi-Harada syndrome.
AB  - AIM: To observe pathophysiological changes in patients with Vogt-Koyanagi-Harada
      (VKH) syndrome using the scanning laser ophthalmoscope (SLO) to perform
      videofunduscopy, and indocyanine green (ICG) and fluorescein videoangiography.
      METHODS: 18 patients diagnosed with VKH syndrome were studied. 15 patients were
      examined in both acute and convalescent phases, and three patients were examined
      in the convalescent phase only. Retrospective review of charts was performed to
      obtain data on visual acuities, clinical findings, and results of cerebrospinal
      fluid cytology and histocompatibility leucocyte antigen D locus testing. RESULTS:
      Videofunduscopy revealed abnormalities in the central macula at the level of the
      retinal pigment epithelium or choroid in 40% of patients in the acute phase and
      83% of patients in the convalescent phase. ICG videoangiography showed irregular
      hypofluorescence (80%), slow or patchy filling (67%), indistinct or fewer
      choroidal vessels (73%), filling defects (73%), and focal leakage (33%) in
      patients in the acute phase. These changes improved with systemic corticosteroid
      treatment, although at least one ICG videoangiographic abnormality persisted into
      the convalescent phase in 83% of patients in the absence of clinical
      inflammation. In contrast, fluorescein videoangiography revealed fewer and
      decreased severity of abnormalities, with greater resolution in the convalescent
      phase when compared with ICG videoangiography. CONCLUSIONS: SLO videofunduscopy
      and videoangiography revealed numerous abnormalities in patients with VKH
      syndrome, many of which persisted well after clinical recovery, suggesting the
      development of permanent morphological changes in the fundus. ICG
      videoangiography was more sensitive than fluorescein videoangiography in
      delineating abnormalities in layers deep to the sensory retina.

PMID- 9924308
TI  - Lens epithelial cell regression on the posterior capsule with different
      intraocular lens materials.
AB  - BACKGROUND/AIMS: Posterior capsular opacification (PCO) is caused by
      proliferation and migration of lens epithelial cells (LECs) across the posterior
      capsule and is the commonest cause of reduced vision after cataract surgery. The
      influence of intraocular lens (IOL) material on the process of LEC migration was
      studied. METHODS: 90 eyes underwent standardised extracapsular surgery, with
      capsulorhexis and "in the bag" IOL placement. They were randomised to receive a
      three piece 6 mm lens of PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort
      Worth, TX, USA). On days 7, 30, 90, 180, and years 1 and 2 high resolution
      digitised retroillumination images were taken of the posterior capsule. The
      presence of LECs was determined at 90 days and 2 years, and their progression or
      regression was established by serial examination of images. RESULTS: LECs were
      seen in 93% of silicone and 97% of PMMA IOLs at 90 days, compared with 46% of
      polyacrylic (p < 0.001). At year 2 LECs were present in all patients with
      silicone or PMMA lenses, whereas 62% of patients with polyacrylic IOLs had LECs
      (p < 0.001). Of those patients with LECs at day 90 LEC regression occurred in 8%
      with silicone IOLs and 15% of PMMA cases, compared with 83% of patients with
      polyacrylic IOLs (p < 0.0001). CONCLUSION: The presence of LECs on the posterior
      capsule was considerably lower with polyacrylic than PMMA or silicone IOLs and
      LEC regression occurred more frequently. The lower incidence of LECs and the
      higher rate of regression may explain why PCO formation appears to be reduced
      with polyacrylic lenses. This has important clinical implications for the
      prevention of PCO.

PMID- 9924309
TI  - Analysis of effects of stimulation in vitro of ovalbumin primed lymph node cells
      on adoptive transfer of experimental immune mediated blepharoconjunctivitis in
      Lewis rats.
AB  - AIM: To analyse the role of stimulation in vitro of lymphocytes on the
      augmentation of experimental immune mediated blepharoconjunctivitis (EC, formerly
      EAC) in Lewis rats induced by adoptive transfer. METHODS: Two weeks after
      immunisation with ovalbumin (OVA), rat draining lymph nodes were collected and 50
      x 10(6) cells were injected into naive syngeneic recipients either directly or
      after culture in vitro with OVA, concanavalin A (Con A), or purified protein
      derivative (PPD) for 3 days. Four days after injection the rats were topically
      challenged with OVA. 24 hours later, they were sacrificed and eyes and spleens
      were harvested for histology and proliferation assay. In some experiments, naive
      recipient rats were irradiated with 7 Gy gamma ray before transfer. The
      expression of adhesion molecules and cytokine profile of OVA primed lymph node
      cells were also investigated. RESULTS: Both infiltrated cell number and
      splenocyte proliferation in the recipients of stimulated cells were higher than
      those of unstimulated cells. In vitro stimulation with OVA or Con A induced a
      severe cellular infiltration, while stimulation with PPD did not. Irradiation
      markedly diminished cellular infiltration. Stimulation in vitro upregulated the
      CD4/CD8 ratio by four times and augmented expression of CD25, I-A, ICAM-1
      molecules on OVA primed lymph node cells by about five times. IFN-gamma was
      detected in OVA primed cells by stimulation in vitro, while IL-4 mRNA was
      extinguished by stimulation in vitro. CONCLUSIONS: Augmentation of EC by
      stimulation in vitro of transferred lymphocytes might depend on the upregulation
      of expression of cell surface molecules and cytokine shift as well as augmented
      antigen specificity.

PMID- 9924310
TI  - Treatment of uveitis with recombinant human interleukin-13.
AB  - AIM: To evaluate the anti-inflammatory cytokine interleukin-13 (IL-13) for the
      treatment of uveitis. METHODS: Uveitis was induced in monkeys by immunisation
      with human retinal S-antigen. Starting at the onset of disease, the animals were
      treated with IL-13 at 25 micrograms/kg, or vehicle control, injected
      subcutaneously once a day for 28 days. Intraocular inflammation was scored by
      indirect ophthalmoscopy for a period of 56 days. Circulating leucocyte levels
      were monitored. RESULTS: Uveitis started unilaterally in all but one animal. IL
      13 inhibited inflammation both in the eyes in which the disease was present when
      the treatment was initiated (p = 0.0001), and in the contralateral initially
      negative eyes (p = 0.0001). After cessation of therapy, there was a progressive
      increase of inflammation in the IL-13 treated group. However, the beneficial
      effect of IL-13 extended into the 4 week follow up period. IL-13 produced an
      increase in circulating polymorphonuclear neutrophils and a decrease in
      lymphocytes. CONCLUSION: Administration of IL-13 appears to be a promising
      modality of treatment for severe uveitis.

PMID- 9924311
TI  - Possible role for nitric oxide releasing nerves in the regulation of ocular blood
      flow in the rat.
AB  - AIM: To investigate the role of nitrergic nerves in the regulation of ocular
      blood flow. METHODS: Conscious, lightly restrained rats were treated with either
      the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI), or the
      nonselective inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and ocular
      blood flow was measured ex vivo from tissue samples, using the fully quantitative
      [14C]-iodoantipyrine technique. RESULTS: In the peripheral circulation, L-NAME
      produced an increase in arterial blood pressure (+22%) while 7-NI had no effect.
      In contrast, both 7-NI and L-NAME produced significant decreases in ocular blood
      flow (-31% and -59% respectively). The ocular vascular resistance calculated from
      ocular blood flow and mean arterial blood pressure increased by 29% following 7
      NI, but by 130% following L-NAME. CONCLUSIONS: Nitric oxide releasing neurons may
      play an important contributory role in regulating ocular blood flow.

PMID- 9924313
TI  - Idiopathic keratoconus in a patient with congenital rubella syndrome.

PMID- 9924314
TI  - Pseudouveitis as a manifestation of hyperlipidaemia.

PMID- 9924312
TI  - Allergic eye disease mechanisms.

PMID- 9924315
TI  - Detection of anticytomegalovirus antibody synthesis in the anterior chamber in
      Vogt-Koyanagi-Harada syndrome.

PMID- 9924316
TI  - Bilateral small retinal infiltrates during rickettsial infection.

PMID- 9924317
TI  - Progressive outer retinal necrosis in a patient with cutaneous non-Hodgkin's T
      cell lymphoma (Sezary syndrome)

PMID- 9924318
TI  - Myopia.

PMID- 9924319
TI  - Automated perimetry by optometrists in patients at low risk of glaucoma.

PMID- 9924321
TI  - Towards a more accurate assessment of the malignant potential in conjunctival
      melanosis.

PMID- 9924320
TI  - Cortically visually impaired children: a need for more study.

PMID- 9924322
TI  - The baby with poor visual contact.

PMID- 9924323
TI  - Visual behaviours of neurologically impaired children with cerebral visual
      impairment: an ethological study.
AB  - BACKGROUND/AIMS: Visual functions of neurologically impaired children with
      permanent cerebral visual impairment (CVI) can be difficult to determine. This
      study investigated the behavioural profile of CVI children by means of
      ethological observations in order to gain a better understanding of their visual
      functions. METHODS: Video registrations of nine subjects who were unable to
      undergo more orthodox methods of visual function testing were observed and
      analysed by an ethologist. RESULTS: A series of behaviours (direct signs) and
      supportive or confirming behavioural elements (indirect signs) indicating some
      visual perception in the children were found. CONCLUSION: Detailed ethological
      observations of visual behaviour were shown to be useful for analysing visual
      functions of children with permanent CVI.

PMID- 9924324
TI  - Simulating binocular visual field status in glaucoma.
AB  - AIMS: To simulate the central binocular visual field using results from merged
      left and right monocular Humphrey fields. To assess the agreement between the
      simulation and the binocular Humphrey Esterman visual field test (EVFT). METHOD:
      59 consecutive patients with bilateral glaucoma each recorded Humphrey 24-2
      fields for both eyes and binocular EVFT on the same visit. EVFT results were used
      to identify patients exhibiting at least one defect (< 10 dB) within the central
      20 degrees of the binocular field. This criterion is relevant to a patient's
      legal fitness to drive in the UK. Individual sensitivity values from monocular
      fields are merged to generate a simulated central binocular field. Results are
      displayed as a grey scale and as symbols representing defects at the < 10 dB
      level. Agreement between patients failing the criterion using the simulation and
      the EVFT was evaluated. RESULTS: Substantial agreement was observed between the
      methods in classifying patients with at least one defect (< 10 dB) within the
      central binocular field (kappa 0.81; SE 0.09). Patients failing this criterion
      using the EVFT results were identified by the binocular simulation with high
      levels of sensitivity (100%) and specificity (86%). CONCLUSIONS: Excellent
      agreement exists between the simulated binocular results and EVFT in classifying
      glaucomatous patients with central binocular defects. A rapid estimate of a
      patient's central binocular field and visual functional capacity can be
      ascertained without extra perimetric examination.

PMID- 9924325
TI  - Relation between size of optic disc and thickness of retinal nerve fibre layer in
      normal subjects.
AB  - AIMS: To evaluate the relation between the optic disc size and the thickness of
      the peripapillary retinal nerve fibre layer (RNFL) in normal Japanese subjects by
      means of scanning laser polarimetry. METHODS: Scanning laser polarimetry was
      performed in 60 normal subjects. One eye of each subject was randomly selected
      for study. Using a scanning laser polarimeter, the integral of RNFL thickness was
      measured totally and regionally within a circular band located 1.75 disc
      diameters from the centre of the optic disc. The correlation between the optic
      disc size and the integral of RNFL thickness was examined. RESULTS: The optic
      disc size showed a significant correlation with the integral of RNFL thickness (R
      = 0.497, p < 0.001). A significant negative correlation was observed between the
      optic disc size and the ratio of inferior integral to total integral of RNFL
      thickness (R = -0.274, p = 0.034). CONCLUSIONS: The cross sectional area occupied
      by the RNF, measured by scanning laser polarimetry increased significantly with
      an increase in optic disc size while the ratio of inferior to total cross
      sectional area decreased significantly. These facts should be considered when one
      evaluates the RNFL thickness in patients with progressive optic neuropathies such
      as glaucoma.

PMID- 9924326
TI  - Longer-term visual outcome of eyes with retinopathy of prematurity treated with
      cryotherapy or diode laser.
AB  - AIMS: Visual outcome of 66 eyes in 37 patients who had undergone treatment with
      either cryotherapy or diode laser for threshold retinopathy of prematurity was
      assessed. METHODS: 17 patients, representing 30 eyes treated with cryotherapy,
      were examined at between 56 and 98 months corrected age (median 68 months). 20
      patients representing 36 eyes treated with diode laser, were examined at between
      30 and 66 months corrected age (median 51 months). Structural outcome was
      categorised as: optimal--flat posterior pole; suboptimal--macular ectopia, optic
      nerve hypoplasia, retinal fold involving the macula, and retinal detachment
      involving the macula. RESULTS: Optimal structural outcome was, in the absence of
      amblyopia, associated with optimal visual acuity (of 6/12 or better) in all
      cases, with most eyes achieving a visual acuity of 6/9 or 6/6. Suboptimal
      structural outcome was invariably associated with suboptimal visual acuity.
      Amblyopia was present in eight out of 20 cryotherapy treated eyes and in five out
      of 26 laser treated eyes with an optimal structural outcome. Refractive errors
      were significantly less in laser treated eyes as was the incidence of
      anisometropic amblyopia. CONCLUSION: Eyes treated with either cryotherapy or
      diode laser for threshold retinopathy of prematurity with optimal structural
      outcome are associated with development of optimal visual acuity--that is, 6/12
      or better. Treatment with either cryotherapy or laser does not in itself reduce
      the visual potential of these eyes.

PMID- 9924327
TI  - Comparison of the safety and efficacy of the fixed combination of
      dorzolamide/timolol and the concomitant administration of dorzolamide and
      timolol: a clinical equivalence study. International Clinical Equivalence Study
      Group.
AB  - AIMS: To compare the tolerability and efficacy of a fixed combination solution of
      dorzolamide/timolol (Cosopt), administered twice daily with the concomitant
      administration of its components, dorzolamide (Trusopt) twice daily and timolol
      (Timoptic) twice daily. METHODS: After a 2 week timolol run in, patients with
      open angle glaucoma or ocular hypertension were randomised (1:1) to receive
      treatment with either the dorzolamide/timolol combination solution twice daily
      (combination) or the dorzolamide solution twice daily plus timolol maleate
      solution twice daily (concomitant) for 3 months. RESULTS: 299 patients were
      entered and 290 patients completed the study. Compared with the timolol baseline,
      additional IOP lowering of 16% was observed at trough (hour 0) and 22% at peak
      (hour 2) at month 3 in both the concomitant and combination groups. The IOP
      lowering effects of the two treatment groups were clinically and statistically
      equivalent as demonstrated by the extremely small point differences (concomitant-
      combination) observed in this study--0.01 mm Hg at trough and 0.08 mm Hg at peak.
      The safety variables of the concomitant and combination groups were very similar.
      Both combination and concomitant therapy were well tolerated and few patients
      discontinued due to adverse effects. CONCLUSIONS: The dorzolamide/timolol
      combination solution administered twice daily is equivalent in efficacy and has a
      similar safety profile to the concomitant administration of the components
      administered twice daily.

PMID- 9924328
TI  - Three year visual outcome for treated stage 3 retinopathy of prematurity:
      cryotherapy versus laser.
AB  - BACKGROUND/AIMS: In the management of retinopathy of prematurity (ROP), several
      studies have demonstrated laser photocoagulation to be as effective as
      cryotherapy in reducing the incidence of unfavourable structural outcome.
      However, few data are available on the functional outcome. The 3 year visual
      acuity outcome of infants treated with laser or cryotherapy in a neonatal unit is
      presented. METHODS: The case notes of 34 infants (64 eyes) treated with
      cryotherapy, between 1989 and 1992, and 32 infants (59 eyes) treated with laser,
      between 1992 and 1995, were reviewed. RESULTS: In the cryotherapy group 69% of
      eyes had a favourable structural outcome. Of these structurally successful eyes
      62.5%, 35.0%, and 33.3% of eyes had visual acuities within normal limits at the
      12 month, 24 month, and 36 month corrected age milestones respectively. In the
      laser group 93% of eyes had a favourable structural outcome. Of these
      structurally successful eyes 96.4%, 66.7%, and 59.5% of eyes had visual acuities
      within normal limits at the 12 month, 24 month, and 36 month corrected age
      milestones respectively. CONCLUSION: In the management of ROP, when laser
      photocoagulation induces a structurally successful result, the potential for
      normal visual acuity development at 3 years is high. Whether the poorer
      functional outcome of the eyes treated with cryotherapy is an artefact of the
      historical nature of the study or as a result of an adverse effect of the
      destructive transcleral application is unknown.

PMID- 9924329
TI  - Screening for abnormal levels of hyperopia in children: a non-cycloplegic method
      with a hand held refractor.
AB  - AIMS: High hyperopia constitutes the majority of refractive errors in large scale
      visual screening at preschool ages. The authors aimed to assess the validity of
      the Retinomax hand held refractor to detect high hyperopia in a refractive
      screening performed without cycloplegia and carried out on children aged 9-36
      months. They considered +1.5 D of manifest hyperopia to be the threshold value
      and abnormal absolute hyperopia to be above +3.5 D. METHODS: Of the 897 children
      screened without cycloplegia, 220 were refracted with cycloplegia. The validity
      of several thresholds of manifest hyperopia was estimated by receiver operating
      characteristic (ROC) curves using cycloplegic measures as a reference. The
      reproducibility of Retinomax measurements was assessed. Normal and quick mode
      measurements were compared using the Wilcoxon test. RESULTS: The manifest
      threshold of +1.5 D offered the best combination of sensitivity (70.2%),
      specificity (94.6%), positive predictive value (78.6%), and negative predictive
      value (91.9%) to disclose abnormal absolute hyperopia. A good agreement was
      obtained between the various measurements using Retinomax on the same subject. In
      the results of this survey, there is no evidence that accommodation is minimised
      in the normal mode of measurement compared with the quick mode. CONCLUSION: The
      Retinomax hand held infrared autorefractor is a suitable instrument to diagnose
      abnormal hyperopia (manifest hyperopia > +1.5 D) in noncycloplegic refractive
      screening at preschool ages. It is suggested as the quick mode of measurement as
      it is more feasible in children (success rate 98.5%).

PMID- 9924330
TI  - Ophthalmological long-term follow up of preterm infants: a population based,
      prospective study of the refraction and its development.
AB  - BACKGROUND: Numerous studies have reported an increased risk of refractive errors
      in prematurely born infants, but only few have been long-term and strictly
      population based. METHODS: A 3.5 year ophthalmological long term follow up of 248
      preterm infants was performed. The infants had been included in a previous
      epidemiological study of retinopathy of prematurity (ROP) (birth weight < or =
      1500 grams). The incidence of refractive errors and development of refraction
      were studied, based on retinoscopies at 6 and 30 months of corrected age.
      RESULTS: The overall incidence of myopia was 8% at 6 months, of which 35% was
      transient, and 10% at 30 months. Of the cryotreated infants, 30-40% were myopic
      at both retinoscopies. The incidence of astigmatism was 52% at 6 months and 26%
      at 30 months. Astigmatism was associated with ROP, but not with cryotreated ROP
      itself. Astigmatism "against the rule" was commoner than astigmatism "with the
      rule". Anisometropia occurred in 6.5% of the infants at 6 months and in 8.4% at
      30 months. The incidence of anisometropia was higher in eyes with ROP,
      particularly in cryotreated eyes, which tended to have high and persistent
      anisometropia. CONCLUSION: The risk of refractive errors is higher in preterm
      infants than in infants born at term, and also prematurely born infants without
      ROP do run an increased risk of having myopia and anisometropia. We recommend
      follow up examinations with retinoscopy for all infants included in screening
      programmes for ROP.

PMID- 9924331
TI  - Disposable contact lens use as a risk factor for microbial keratitis.
AB  - AIMS: A case-control study was performed to evaluate soft contact lens (SCL) wear
      modality as a risk factor for microbial keratitis. METHODS: Contact lens wearers
      presenting as new patients to Moorfields Eye Hospital accident and emergency
      department during a 12 month period completed a self administered questionnaire
      detailing demographic data and contact lens use habits. Cases were patients with
      a clinical diagnosis of SCL related microbial keratitis. Controls were SCL users
      attending with disorders unrelated to contact lens wear. Odds ratios (estimates
      of relative risks) and 95% confidence limits (CL) were calculated through
      multivariable logistic regression analysis. RESULTS: There were 89 cases and 566
      controls. A substantially increased risk with 1-4 weekly disposable SCL compared
      with non-disposable SCL was identified among both daily wear (DW) (odds ratio =
      3.51, 95% CL 1.60-7.66, p = 0.002) and extended wear (odds ratio 4.76, 95% CL
      1.52-14.87, p = 0.007) users after adjustment for demographic, lens use and
      hygiene variables. Other significant factors among DW users were "occasional"
      overnight use, use of chlorine based (as opposed to other chemical) systems in
      combination with poor storage case hygiene, and irregular disinfection.
      CONCLUSION: Properties of some disposable SCL may be partly responsible for these
      excess risks. It is also possible, however, that this finding is largely a
      reflection of widespread complacency among patients and practitioners with
      respect to disposable SCL fitting and use.

PMID- 9924332
TI  - Corneoscleral transplantation for end stage corneal disease.
AB  - AIM: To describe the prognosis and complications of corneoscleral transplantation
      in the management of end stage eye disease. METHODS: A case series is presented
      of 23 patients who have undergone corneoscleral transplantation (> or = 11 mm).
      Patients were examined for visual acuity, intraocular pressure, recurrence of
      disease process, epithelialisation of the graft, signs of rejection, and other
      potential complications. RESULTS: 14 patients retained their eye, with six
      maintaining a clear graft. Vision ranged from 6/30 to no perception of light. 13
      patients developed glaucoma (range 25-69 mm Hg), with six patients requiring
      surgical intervention. 12 patients required tarsorrhaphy to promote
      epithelialisation. Only two grafts resulted in typical rejection. CONCLUSIONS:
      The technique of corneoscleral transplantation can salvage otherwise end stage
      eye disease, but the results are poor with respect to maintenance of vision.
      These patients need careful follow up because of potential complications of
      glaucoma, epithelial defects, rejection, and recurrence of disease.

PMID- 9924333
TI  - Severe form of juvenile corneal stromal dystrophy with homozygous R124H mutation
      in the keratoepithelin gene in five Japanese patients.
AB  - AIM: To confirm the mutation of the keratoepithelin gene in patients with a
      severe form of superficial juvenile granular corneal dystrophy (GCD). METHODS:
      Five Japanese probands in whom GCD was diagnosed after histopathological
      examination and who developed severe manifestations of GCD in their first decade
      of life were investigated. Other affected family members of two probands were
      also examined. All probands were the offspring of consanguineous parents. DNA was
      extracted from their peripheral blood leucocytes and mutational analysis of the
      gene was performed by the polymerase chain reaction and direct sequencing.
      RESULTS: Four of the five probands underwent their first keratectomy or
      keratoplasty in their teens and subsequently underwent a second or third
      keratoplasty. Each proband had a homozygous G-->A transition at codon 124,
      replacing Arg-->His, of the keratoepithelin gene. Their moderately affected
      family members were heterozygous for the mutation. CONCLUSIONS: This finding
      suggests that the severity of the corneal phenotype depends on the dose effect of
      the mutant gene.

PMID- 9924334
TI  - Randomised prospective masked study comparing patient comfort following the
      instillation of topical proxymetacaine and amethocaine.
AB  - AIMS: To evaluate the claim that topical proxymetacaine produces little or no
      discomfort on instillation by comparing it against topical amethocaine. METHODS:
      This randomised, masked, double blind, prospective study involved 53 consecutive
      patients. Each patient received one drop of amethocaine 0.5% in one eye and one
      drop of proxymetacaine 0.5% in the other. The duration of the stinging sensation
      and degree of discomfort (using descriptive and a linear analogue method) for
      each topical anaesthetic was assessed. RESULTS: The mean duration of stinging was
      3.2 seconds for proxymetacaine and 22.1 seconds for amethocaine the difference
      being statistical significant (p < 0.001). The mean descriptive discomfort score
      was 2.6 for proxymetacaine and 14.2 for amethocaine (p = 0.01). The mean linear
      analogue score was 5.8 for proxymetacaine and 35.6 for amethocaine (p < 0.001).
      Proxymetacaine had a successful tonometry rate of 93% and amethocaine 98%.
      CONCLUSION: This clinical study confirms that proxymetacaine is more comfortable
      on instillation than amethocaine. Minimising unnecessary patient discomfort is
      not only ideal, but encourages cooperation in apprehensive patients especially in
      children.

PMID- 9924335
TI  - Modified Bagolini striated glass test: clinical applications of starlight test in
      binocular visual field screening.
AB  - AIM: To introduce the "starlight" test which was devised to check binocular
      vision in normal conditions of seeing in a rapid, easy, and cost effective manner
      and to estimate the possibility of its clinical use in screening the binocular
      visual field of patients. METHOD: The Bagolini striated glass test consists of
      optically plano lenses with imperceptible parallel scratches that barely blur the
      environment but produce two perpendicular luminous stripes (right eye stripe of
      45 degrees and left eye stripe of 135 degrees) when subjects with normal
      binocular vision view one light source. Unlike the original Bagolini test, the
      starlight test uses three light sources in horizontal or vertical lines according
      to the testing purposes and the subject is asked to fixate upon the centre light.
      Through Bagolini glasses, the subject observes the resulting grid-like pattern
      and the state of binocular visual field of the subject can be roughly estimated.
      RESULTS: Normal subjects and patients with strabismus, visual field loss from
      intracranial diseases, glaucoma, retinitis pigmentosa, and functional visual loss
      were examined using the starlight test and findings from each case were
      discussed. CONCLUSIONS: The starlight test, which was made by hand at a low cost,
      is a simple test that can be used clinically. It provides information about the
      state of binocular vision of patients in normal conditions of seeing. It is also
      useful because it enables the examiner to share similar experiences with the
      examinee. The results suggest it can be effective in visual field screening.

PMID- 9924336
TI  - Automatic full field analysis of perfusion images gained by scanning laser
      Doppler flowmetry.
AB  - BACKGROUND: Scanning laser Doppler flowmetry (SLDF) enables the measurement of
      the laser Doppler frequency shift in retinal tissue. This process allows the
      quantification of retinal and optic nerve head perfusion in an area of 2.7 mm x
      0.7 mm within 2 seconds and with a spatial resolution of 10 microns x 10 microns.
      Owing to the local heterogeneity of the retinal microcirculation itself and to
      heart associated pulsation the capillary retinal blood flow depends on location
      and time. Because of technical limitations measurements of flow are only valid in
      retinal points with adequate brightness and focus, and away from big vessels. To
      include the heart beat associated pulsation and the spatial heterogeneity of
      retinal blood flow into the evaluation of blood flow an algorithm was developed
      examining automatically the whole SLDF perfusion image. AIM: To report
      intraobserver reliability and interobserver reliability of a new method for
      analysing automatically full field perfusion images. METHOD: The base of blood
      flow calculation by the automatic full field perfusion image analyser (AFFPIA)
      was 16,384 intensity time curves of all pixels of the whole perfusion image
      gained by the SLDF. AFFPIA calculates the Doppler frequency shift and the
      haemodynamic variables flow, volume, and velocity of each pixel. The resulting
      perfusion image was processed with respect to (1) underexposed and overexposed
      pixels, (2) saccades, and (3) the retinal vessel tree. The rim area and the
      saccades were marked interactively by the operator. The capillaries and vessels
      of the retinal vessel tree were identified automatically by pattern analysis.
      Retinal vessels with a diameter greater than 30 microns, underexposed or
      overexposed areas, and saccades were excluded automatically. Based on the whole
      perfusion image total mean flow, total mean volume, total mean velocity, standard
      deviation, cumulative distribution curve of flow, and the capillary pulsation
      index were calculated automatically. Heart beat associated pulsation of capillary
      blood flow was estimated by plotting the mean capillary flow of each horizontal
      line against time. Intraobserver reliability was estimated by measuring 10 eyes
      of 10 subjects on five different days by one observer. Interobserver reliability
      of AFFPIA was evaluated by analysing 10 perfusion maps by five different
      operators. To find a baseline of retinal blood flow, perfusion maps of 67 eyes of
      normal subjects with a mean age of 40.4 (SD 15) years were evaluated by AFFPIA.
      RESULTS: The coefficient of reliability of the intraobserver reproducibility of
      flow was 0.74. The coefficient of reliability of the interobserver
      reproducibility was 0.95. The juxtapapillary retinal capillary flow was
      temporally 484 (SD 125), nasally 450 (117); the rim area capillary flow was 443
      (110). The mean capillary pulsation index of retinal flow was 0.56 (0.14).
      CONCLUSION: Retinal blood flow evaluation by the AFFPIA increases significantly
      the interobserver reliability compared with conventional evaluation of 100
      microns x 100 microns areas in SLDF images with the original Heidelberg retina
      flowmeter software. The intraobserver reliability of AFFPIA was in the same range
      as conventional evaluation.

PMID- 9924337
TI  - Use of scanning laser ophthalmoscopy to monitor papilloedema in idiopathic
      intracranial hypertension.
AB  - AIMS: To determine the sensitivity of confocal scanning laser ophthalmoscopy
      (SLO) in detecting clinically significant changes in papilloedema secondary to
      idiopathic intracranial hypertension (IIH) and the correlation with visual field
      loss. METHODS: Eight patients--three new, two recurrent, and three chronic cases
      of IIH--were examined over a 9 month period with SLO (Heidelberg retina
      tomograph) of optic nerve head and 30-2 Humphrey visual fields (six cases). Optic
      disc swelling (volume) was assessed in each eye using a circular contour line
      placed around the swollen optic nerve head on the mean image of three topographic
      images. Nine volume measurements from single images in each eye of every patient
      were performed on one occasion to assess repeatability. RESULTS: In the five
      acute cases optic disc volumes (range 1-16 mm3) decreased with treatment to
      stable, normal levels. Three of these had mild, reproducible, field defects which
      resolved. Two chronic cases had stable or fluctuating disc volume with no
      detectable change in grade of papilloedema and mild field loss. In one case which
      underwent theco-peritoneal shunting both disc volume and field worsened,
      indicating therapeutic failure. Both improved postoperatively. CONCLUSIONS: SLO
      has a high sensitivity for detecting small changes in disc volumes and correlates
      closely with visual field change in the short term. It can confirm therapeutic
      failure by detecting stable or increasing disc volume. Decreasing volume may
      indicate resolution of papilloedema or secondary optic atrophy, so accompanying
      funduscopy and visual fields remain essential.

PMID- 9924338
TI  - Azithromycin for ocular toxoplasmosis.
AB  - AIMS: To investigate the efficacy of azithromycin in patients with ocular
      toxoplasmosis. METHODS: 11 immunocompetent patients with ocular toxoplasmosis
      were treated with azithromycin (500 mg the first day, followed by 250 mg/day for
      5 weeks). Ocular and systemic examinations were performed during active retinitis
      episodes and all patients were followed for at least 1 year. RESULTS: The
      intraocular inflammation disappeared within 4 weeks in seven patients, including
      two cases with progressive retinitis despite previous treatment with
      pyrimethamine, sulphadiazine, and folinic acid. Recurrence of retinitis occurred
      in three patients (27%) within the first year of follow up. No systemic side
      effects of azithromycin were encountered. CONCLUSION: These results indicate that
      although azithromycin cannot prevent recurrent disease it may be an effective
      alternative for patients with ocular toxoplasmosis who cannot tolerate standard
      therapies.

PMID- 9924339
TI  - Flashing lights in thyroid eye disease: a new symptom described and (possibly)
      explained.
AB  - BACKGROUND/AIMS: Some patients with restrictive thyroid ophthalmopathy, referred
      for consideration of extraocular muscle surgery, complained of flashing lights in
      the superior visual field on upgaze. The frequency was assessed and the
      pathogenesis of this previously unreported symptom explored. METHODS: 30 patients
      were recruited, all of whom had tight inferior recti and were in the burnt out
      phase of thyroid eye disease. They were directly questioned regarding any
      symptoms of photopsia and their records were examined with respect to disease
      status and treatment, ocular motility, intraocular pressure, retinal status, and
      surgical intervention. Magnetic resonance imaging (MRI) and cine MRI scans were
      reviewed for evidence of globe compression. The frequency of symptoms was
      compared with an age and sex matched control group. RESULTS: Three patients
      spontaneously complained of flashing lights. A further nine patients had this
      symptom when directly questioned. 18 patients had no symptoms. None of the 33
      control patients had symptoms on direct questioning. Sagittal MRI and cine MRI
      failed to demonstrate globe compression by the inferior rectus muscle even in
      cases that showed an intraocular pressure rise in upgaze. CONCLUSION: A new
      symptom of flashing lights in upgaze has been identified in thyroid eye disease
      patients with tight inferior recti. It is suggested that the lights are likely to
      be phosphenes as a result of either compression of the globe by a tight inferior
      rectus or traction on the insertion of the inferior rectus. The small amount of
      globe compression required to produce phosphenes seems to be beyond the
      resolution limit of MRI.

PMID- 9924340
TI  - Intraocular lens implants and risk of endophthalmitis.
AB  - AIM: To investigate the possible association between the use of three piece
      foldable silicone polypropylene (SPP) intraocular lenses (IOLs) and an increased
      risk of postoperative endophthalmitis. METHODS: A retrospective analysis was
      conducted of all cases of postoperative endophthalmitis following
      phacoemulsification surgery in a single unit over a 3 year period. The incidence
      of postoperative endophthalmitis in eyes with SPP IOLs was compared with the
      incidence in eyes with single piece polymethylmethacrylate (PMMA) IOLs. RESULTS:
      772 cataract extractions by phacoemulsification were performed. One (0.16%) of
      the 622 patients with PMMA IOLs developed endophthalmitis. Excluding one patient
      who had aplastic anaemia, five (3.33%) of 150 patients with SPP IOLs developed
      endophthalmitis. The relative risk for postoperative endophthalmitis associated
      with the use of the SPP IOL compared with the PMMA IOL was 20.1 (p = 0.015).
      CONCLUSION: This study adds further evidence to the concept that SPP IOLs can be
      a significant risk factor in the development of postoperative endophthamitis.

PMID- 9924341
TI  - MIB-1 and PC-10 immunostaining for the assessment of proliferative activity in
      primary acquired melanosis without and with atypia.
AB  - AIMS: To compare the proliferative activity of intraepithelial melanocytes in
      primary acquired melanosis (PAM) without atypia and PAM with atypia by
      immunohistochemical staining for the Ki-67 antigen and the proliferating cell
      nuclear antigen (PCNA). METHODS: Formalin fixed, paraffin embedded sections from
      35 archival specimens of PAM without atypia (n = 19) and with atypia (n = 16)
      were studied by immunostaining with MIB-1 and PC-10 monoclonal antibodies that
      react with the Ki-67 antigen and PCNA respectively. The results were calculated
      as the mean number of positive cells per eyepiece grid. All specimens were
      evaluated by two masked observers, and the interobserver reproducibility was
      assessed. RESULTS: The means of the positive cell count in PAM with atypia were
      significantly higher compared with PAM without atypia for both observers, in both
      the PC-10 and the MIB-1 stained sections. In a linear least square model that
      estimated the interobserver and between group variation, the difference of MIB-1
      and PC-10 positive cell count between PAM without and with atypia remained highly
      significant. The difference between the observers was not significant.
      CONCLUSIONS: Immunostaining with MIB-1 and PC-10 demonstrated that PAM with
      atypia has higher proliferative activity than PAM without atypia. This method was
      found to be reproducible between different observers.

PMID- 9924342
TI  - Gefarnate increases PAS positive cell density in rabbit conjunctiva.
AB  - AIMS: The effects of three drugs for the treatment of gastritis and gastric ulcer
      -gefarnate, ecabet sodium, and troxipide--on periodic acid Schiff (PAS) positive
      cell density in rabbit conjunctiva in vivo were investigated. METHODS: Eye drops
      containing gefarnate (0.1%, 1%), ecabet sodium (0.1%, 1%), or troxipide (0.1%,
      1%) were instilled in both eyes of rabbits, six times a day for 7 days. On the
      eighth day, filter paper was gently pressed on the bulbar and palpebral
      conjunctiva, and impression cytology was performed with PAS staining. Three
      points in each specimen were selected randomly, and PAS stained cells were
      counted. RESULTS: The instillation of gefarnate increased PAS positive cell
      density significantly at the concentration of 1% (p < 0.05). In contrast,
      instillation of ecabet sodium or troxipide failed to change PAS positive cell
      density. CONCLUSIONS: These results demonstrated that gefarnate stimulates PAS
      positive cell density in rabbit conjunctiva.

PMID- 9924343
TI  - Evaluation of loss of heterozygosity and microsatellite instability in human
      pterygium: clinical correlations.
AB  - AIMS: To evaluate the incidence of loss of heterozygosity (LOH) and
      microsatellite instability (MI) in pterygia and their possible correlation with
      clinical variables. METHODS: 50 pterygia, blood, and conjunctival specimens were
      obtained. A personal and family history was recorded for each patient.
      Amplification of 15 microsatellite markers at regions 17p, 17q, 13q, 9p, and 9q
      was performed using the polymerase chain reaction. The electrophoretic pattern of
      DNA from pterygia was compared with the respective pattern from blood and
      conjunctiva. RESULTS: LOH incidence was the highest at 9p (48%), followed by 17q
      (42%). Only three cases displayed MI. LOH incidence at individual markers was
      positively correlated with recurrence (D9S59, p = 0.11 and D9S270, p = 0.16),
      family history of neoplasia (D13S175, p = 0.09), altitude of present residence
      (D9S112, p = 0.1), duration of the existence of pterygium (D9S144, p = 0.06), and
      inversely correlated with age (D9S59, p = 0.09). Concerning chromosome arms, LOH
      was positively correlated with the altitude of present residence (13q and 17p, p
      = 0.03) and duration of the existence of pterygium (13q and 17p, p = 0.09).
      CONCLUSIONS: LOH is a common event whereas MI is a very uncommon one at the
      examined markers in pterygium, indicating the presence of putative tumour
      suppressor genes implicated in the aetiopathogenesis of the disease. The fact
      that LOH at 9q31-33 was more frequent in recurrent pterygia and also correlated
      with known risk factors such as young age and high altitude of residence, implies
      a possible predictive value of this finding for postoperative recurrence.

PMID- 9924345
TI  - The safety of laser pointers: myths and realities.

PMID- 9924344
TI  - Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with
      Sorsby's fundus dystrophy or retinitis pigmentosa.
AB  - BACKGROUND/AIMS: Tissue inhibitor of metalloproteinases-3 (TIMP-3) is normally
      synthesised by the retinal pigment epithelium (RPE) and deposited in Bruch's
      membrane. Mutations in the TIMP3 gene cause Sorsby's fundus dystrophy (SFD),
      which is characterised by thickening of Bruch's membrane, choroidal
      neovascularisation, and photoreceptor degeneration. To elucidate the role of TIMP
      3 in human retinal degenerative diseases, we immunolocalised TIMP-3 in eyes with
      SFD caused by the Ser-181-Cys TIMP3 gene mutation or retinitis pigmentosa (RP;
      not caused by TIMP3 mutations). METHODS: Standard light microscopic
      immunocytochemistry, including antigen retrieval, was used to localise TIMP-3 in
      paraffin sections of human eyes: two with SFD, three with different genetic forms
      of RP, and two normal. RESULTS: In the SFD eyes, the thickened Bruch's membrane
      was strongly TIMP-3 positive except where RPE cells had degenerated. Similarly,
      in the RP eyes, Bruch's membrane was TIMP-3 positive except where RPE cells were
      lost, consistent with ongoing RPE mediated turnover of TIMP-3 in this region. In
      areas of total photoreceptor loss, migrated RPE cells formed cuffs around blood
      vessels in the RP retinas. Thick, TIMP-3 positive extracellular matrix (ECM)
      deposits associated with the migrated RPE cells occluded some vascular lumina,
      correlating with the observed loss of inner retinal neurons in RP. CONCLUSIONS:
      TIMP-3 is a component of the increased ECM sequestered in Bruch's membrane in
      SFD. Further information is needed on normal TIMP-3/ECM interactions in Bruch's
      membrane and the effect of mutant TIMP-3 on this process. The finding of TIMP-3
      accumulations in retinas with RP not caused by TIMP-3 mutations emphasises the
      importance of ECM remodelling in normal and diseased human eyes.

PMID- 9924346
TI  - Ultrasound biomicroscopic images of the anterior chamber angle of a patient with
      posterior polymorphous dystrophy.

PMID- 9924347
TI  - HIV retinopathy at seroconversion.

PMID- 9924348
TI  - Xerophthalmia and short bowel syndrome.

PMID- 9924349
TI  - Visual impairment due to bilateral corneal endothelial failure following
      simultaneous bilateral cataract surgery.

PMID- 9924350
TI  - Symptomatic acute raised IOP following hemodialysis in a patient with end stage
      renal failure.

PMID- 9924351
TI  - Episcleral melanoma without conjunctival or uveal involvement.

PMID- 9924352
TI  - Intraocular metastasis of endodermal sinus tumour.

PMID- 9924353
TI  - Congenital lenticular pigmentation.

PMID- 9924354
TI  - Fluorescein and indocyanine green angiography in arteritic anterior ischaemic
      optic neuropathy.

PMID- 9924355
TI  - Intraocular and extraocular bleeding after intracameral injection of tissue
      plasminogen activator.

PMID- 9924356
TI  - Visual limitations assessment in patients with glaucoma.

PMID- 9924357
TI  - Insulin-like growth factor type 1--friend or foe?

PMID- 9924358
TI  - Pulsatile ocular blood flow.

PMID- 9924359
TI  - Preschool vision screening: a recent report calls for a halt.

PMID- 9924360
TI  - Evidence that upregulation of serum IGF-1 concentration can trigger acceleration
      of diabetic retinopathy.
AB  - BACKGROUND: Acute reduction of chronic hyperglycaemia can accelerate early
      diabetic retinopathy. In adolescent patients with Mauriac's syndrome, this
      phenomenon is related to an upregulation of subnormal serum IGF-1 levels. AIM: To
      obtain longitudinal data on serum IGF-1 and retinopathy status in poorly
      controlled adult insulin dependent (type 1) diabetic patients without Mauriac's
      syndrome, in whom hyperglycaemia is reduced by intensive insulin therapy.
      METHODS: Four patients with chronic severe insulin deficiency and early micro
      angiopathy were studied prospectively. Changes in plasma glucose, HbA1c, serum
      IGF-1 levels, proteinuria, retinopathy, and clinical status were followed up
      closely. RESULTS: Reducing hyperglycaemia from > 16 mmol/l (equivalent to HbA1c >
      11%) to < 10 mmol/l (HbA1c < 8%) within 5 months increased serum IGF-1 levels by
      70-220%. While proteinuria and symptomatic neuropathy regressed, retinopathy
      progressed from the mild to the severe non-proliferative stage with maculopathy
      (n = 4), and to the proliferative stage (n = 1). Laser coagulation was commenced
      upon the appearance of sight threatening macular oedema (n = 4). CONCLUSION:
      Upregulation of serum IGF-1 preceding retinal deterioration in these patients
      suggests a cause-effect relation, consistent with earlier experimental and
      clinical data.

PMID- 9924361
TI  - Pulsatile ocular blood flow investigation in asymmetric normal tension glaucoma
      and normal subjects.
AB  - AIMS: This study was designed to investigate pulsatile ocular blood flow (POBF)
      in normal tension glaucoma (NTG) patients and in normal controls. NTG patients
      with unilateral field loss were evaluated to compare POBF values between eyes
      with and without field loss. METHODS: POBF measurements from more than 1500
      subjects were collected during a period of 6 months from six optometric centres.
      Subjects with systemic vascular diseases (such as systemic hypertension and
      diabetes), ophthalmic diseases, a positive family history of glaucoma, and those
      individuals receiving treatment with systemic beta blockers were excluded on the
      basis of a questionnaire. For comparison, 95 NTG patients with unilateral field
      loss, selected from 403 consecutive patients with NTG, underwent POBF testing.
      For each individual age, sex, intraocular pressure, refraction, and pulse rate
      were entered into a database. RESULTS: Data from 777 subjects were included in
      the analysis. POBF measurements of patients and subjects were compared allowing
      for differences in age, sex, intraocular pressure, refraction, and pulse rate.
      POBF was significantly lower in eyes of NTG patients with and without field loss
      (p < 0.001 and p = 0.01 respectively). Eyes of NTG patients with field loss
      showed significantly lower POBF than the contralateral eyes with normal field (p
      < 0.001). CONCLUSIONS: POBF was significantly lower in eyes of NTG patients with
      and without field loss than in normal subjects, suggesting that differences in
      ocular blood perfusion are relevant to the development of NTG and are detectable
      from the early stage of the disease. Furthermore, the finding of lower POBF in
      NTG eyes with field loss than in the contralateral eyes with normal field
      suggests that haemodynamic differences between fellow eyes contribute to
      determine the side of onset of the disease.

PMID- 9924362
TI  - Cyclosporin A therapy in refractory non-infectious childhood uveitis.
AB  - AIMS: To assess the immunosuppressive efficacy, steroid sparing effect and
      adverse effects of cyclosporin A (CsA) therapy in refractory non-infectious
      childhood uveitis. METHODS: A retrospective case series review of the medical
      records of children on CsA therapy attending a tertiary referral centre for
      refractory endogenous uveitis was performed. Low dose (< or = 5.0 mg/kg/day) CsA
      therapy was started either as monotherapy or in combination with other agents.
      The CsA immunosuppressive efficacy was assessed by visual acuity and binocular
      indirect ophthalmoscopy (BIO) score outcomes and steroid sparing effect by growth
      charts and ability to withdraw or maintain a low steroid dose. Possible CsA
      adverse effects were monitored by routine biochemistry (including serum
      creatinine) and haematological tests, blood pressure recordings, and symptoms.
      RESULTS: 14 patients (25 eyes, 10 males, four females) were recruited with
      steroid failure as the most common CsA indication. Age (mean (SD)) at start of
      CsA therapy was 8.7 (4.1) years with a duration of CsA therapy of 20.9 (range 3.5
      88.3) months at a maintenance CsA dose of 4.0 (1.0) mg/kg/day. From baseline,
      visual acuity improved or was maintained in 23 (92%) eyes and BIO score improved
      in 19 (76%) eyes. Height centiles were preserved and the maintenance prednisolone
      dose was 6.3 (3.3) mg/day, where required, in 10 (71%) patients. Nephrotoxicity
      was not observed, with transient systemic hypertension developing in one patient.
      Minor adverse effects were more common but were well tolerated. CONCLUSIONS:
      Cyclosporin A therapy is effective and safe in the medium term, if closely
      monitored, in refractory non-infectious childhood uveitis.

PMID- 9924363
TI  - Bilateral involvement by age related maculopathy lesions in a population.
AB  - AIMS: To describe the influences of age and sex on the frequency of bilateral age
      related macular degeneration (AMD) and age related maculopathy (ARM) lesions.
      METHODS: The Blue Mountains Eye Study examined 3654 older Australians, 82% of
      permanent residents living in an area west of Sydney. Stereo macular photographs
      were graded for AMD (neovascular maculopathy and geographic atrophy) and early
      ARM lesions (soft drusen, reticular drusen, hyperpigmentation, and
      hypopigmentation). RESULTS: Among 230 gradable cases of AMD or early ARM, 183
      (80%) were bilateral. For AMD, 39/69 cases (57%) were bilateral, while for early
      ARM, 123/161 cases (77%) had signs in both eyes. Of the individual lesions,
      reticular drusen (91%) and indistinct soft drusen (79%) were most frequently
      present in both eyes. Geographic atrophy was bilateral in 56%, neovascular AMD in
      40%, and distinct soft drusen in 47%, while hyperpigmentation was bilateral in
      38% and hypopigmentation in only 28% of cases. A consistent age related increase
      in bilateral distribution was observed for most lesions. After adjusting for
      effects of age, current smoking, and AMD family history AMD and ARM component
      lesions, except for soft drusen, were more frequently bilateral in women. This
      sex difference was significant only for neovascular AMD, odds ratio 7.7 (95%
      confidence intervals 1.3-46.7). An AMD family history was more frequently
      reported in cases with bilateral involvement. CONCLUSIONS: This study has
      documented differences in the age related bilaterality of individual ARM
      components with higher bilateral rates for reticular or indistinct soft drusen
      compared with other lesions. The increased bilaterality of most ARM lesions among
      women is likely to contribute to the increased age adjusted risk of AMD blindness
      found in women.

PMID- 9924364
TI  - Risk of developing CMV retinitis following non-ocular CMV end organ disease in
      AIDS patients.
AB  - AIM: To describe the risk of developing cytomegalovirus (CMV) retinitis after a
      first episode of extraocular CMV disease in AIDS patients. METHODS: A review of
      the clinical records of 20 AIDS patients, without CMV retinitis, with
      histologically confirmed extraocular CMV disease, was performed. The main outcome
      measures were occurrence of CMV retinitis, time to development of CMV retinitis,
      relation to maintenance therapy, and survival. RESULTS: A CMV retinitis was
      diagnosed in 17 of 20 (85%) patients with an immunohistologically confirmed
      diagnosis of extraocular CMV disease after a mean follow up of 6.4 months. Four
      patients received maintenance therapy. Three of them developed retinitis after a
      mean of 9.6 months (range 2-16 months). Sixteen did not receive maintenance and
      retinitis was diagnosed in 14 of them after a mean of 5.7 months (range 2-11
      months). Mean survival was 9.9 months after the diagnosis of extraocular disease,
      and 4.5 months after the diagnosis of retinitis. In the four patients receiving
      maintenance therapy, mean survival was 11.5 months, and in the 16 other patients
      mean survival was 9.5 months. Patients did not receive protease inhibitors.
      CONCLUSION: In the preprotease inhibitor era extraocular CMV disease strongly
      predisposes to the subsequent development of CMV retinitis. Although maintenance
      therapy did not prevent the occurrence of retinitis, the time period between both
      events seems to lengthen considerably. In patients receiving maintenance survival
      is also longer.

PMID- 9924365
TI  - Effect of plasma colloid osmotic pressure on intraocular pressure during
      haemodialysis.
AB  - BACKGROUND: In a previous case report, it was shown that an increase in plasma
      colloid osmotic pressure induced by the removal of fluid during haemodialysis was
      instrumental in decreasing intraocular pressure. The relation between changes in
      intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and
      body weight before and after haemodialysis is evaluated. METHODS: Intraocular
      pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight
      were evaluated before and after haemodialysis in 36 patients. RESULTS:
      Intraocular pressure and plasma osmolarity both decreased significantly after
      haemodialysis (p < 0.0001). Plasma colloid osmotic pressure increased
      significantly after haemodialysis (p < 0.0001). Body weight decreased
      significantly because of the removal of fluid during haemodialysis (p < 0.0001).
      No significant correlation was found between the change in intraocular pressure
      and that in plasma osmolarity (r = -0.206, p = 0.2297), whereas the change in
      intraocular pressure was correlated with the change in plasma colloid osmotic
      pressure (r = -0.510, p = 0.0012) and the change in body weight (r = 0.534, p =
      0.0006). A significant correlation was found between the change in plasma colloid
      osmotic pressure and that in body weight (r = -0.756, p < 0.0001). CONCLUSION:
      The change in intraocular pressure was inversely correlated with the increase in
      plasma colloid osmotic pressure caused by the removal of fluid during
      haemodialysis.

PMID- 9924366
TI  - Prevalence and management of elevated intraocular pressure in patients with
      Graves' orbitopathy.
AB  - AIMS: To investigate the prevalence and to discuss the necessity of treating
      elevated intraocular pressures (IOP) in patients with Graves' orbitopathy (GO).
      In addition, to study the effects of orbital decompression and extraocular muscle
      surgery on IOP. METHODS: The records of consecutive patients with GO referred in
      a 5 year period were studied and those selected, in which glaucoma medication had
      been prescribed, or a diagnosis of primary open angle glaucoma (POAG) or of
      ocular hypertension (> or = 22 mm Hg) (OH) had been made. The necessity of
      treating these patients with glaucoma medication was questioned and the effects
      of corticosteroids, orbital decompression, and extraocular muscle surgery on the
      IOP were evaluated. RESULTS: Of 482 patients with GO, 23 (4.8%) met the inclusion
      criteria. Four patients (0.8%) had POAG, four had elevated IOPs and visual field
      defects consistent with dysthyroid optic neuropathy, and 15 (3.1%) had only
      elevated IOPs. Five patients with OH showed a permanent drop of IOP after orbital
      decompression, two had a marked decrease of their IOP after recession of the
      inferior rectus muscle. CONCLUSIONS: POAG has the same prevalence in the general
      Dutch population as in the GO subgroup. The combination of elevated IOPs and
      visual field defects in GO patients may be attributed to other mechanisms than
      obstructed aqueous outflow in the trabecular meshwork and should be treated
      accordingly. Orbital decompression and extraocular muscle surgery may lower the
      IOP in patients with GO.

PMID- 9924367
TI  - Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high
      tension primary open angle glaucoma.
AB  - BACKGROUND: Ocular pulse amplitude (OPA) is reduced in normal tension primary
      open angle glaucoma (NTP) patients when compared with healthy age matched
      controls (CTL) while increased OPA appears to protect ocular hypertensive
      patients from visual field loss. If NTP is accompanied by vasospasm, as in
      roughly half of the primary open angle glaucoma (POAG) population (independent of
      intraocular pressure, IOP), calcium channel blockers increase OPA and thus
      stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but
      do not activate (compromised) ocular perfusion. METHODS: The influence of
      dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three
      times daily, one eye) on OPA, IOP, blood pressure, and heart rate was
      investigated in a randomised, prospective, masked clinical trial assessing the
      acute effects of dorzolamide v placebo before and 2 days after application in 33
      cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who
      provided informed consent. RESULTS: Following application of dorzolamide (D) IOP
      (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5) and in CTLD (16.0 (0.5)/12.3
      (0.5)) was highly significantly (p < 0.001) reduced and was significantly (p <
      0.03) reduced in vehicle (V) treated eyes (HTPv: 20.3 (0.4)/19.0 (0.4)) and CTLv:
      15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA
      (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was
      significantly (p < 0.05) increased and unaffected in vehicle treated eyes when
      compared with respective baseline measurements. Systemic perfusion variables were
      also unchanged. CONCLUSION: Dorzolamide increased OPA in HTP and CTL. Drugs
      stimulating OPA may improve prognosis of POAGs.

PMID- 9924368
TI  - Correlation between Octopus perimetry and fluorescein angiography after strontium
      90 plaque brachytherapy for subfoveal exudative age related macular degeneration.
AB  - AIM: To evaluate the correlation between the central visual field and changes in
      fluorescein angiography and fundus photography in patients treated with strontium
      plaque radiotherapy for subfoveal exudative age related macular degeneration
      (AMD). METHODS: Octopus program 34 automated static perimetry, fluorescein
      angiography, and colour fundus photography were performed on 19 patients at
      baseline and at 12 months after strontium-90 plaque therapy. A schematic picture
      outlining the areas of hyperfluorescent neovascular membranes and subretinal
      blood was drawn of a projected 30 degrees fundus fluorescein angiogram. This
      drawing was superimposed on the size adjusted Octopus visual field. The changes
      in retinal sensitivity were calculated and related to angiographic changes.
      RESULTS: Three of the 19 patients had a reliability factor (RF) > 15% and were
      excluded from further analysis. In the remaining 16 patients the mean defect (MD)
      and loss variance (LV) values remained unchanged in patients showing regression
      of the choroidal neovascular membrane (CNVM) to irradiation at 12 months. MD was
      7.7 (SD 1.7) at baseline and 7.6 (1.9) at 12 months (p = 0.86), and LV was 32.6
      (13.9) at baseline and 32.4 (15.7) at 12 months (p = 0.94). However, in patients
      with progression of the CNVM at 12 months, both the MD and LV increased
      significantly during the 12 month follow up (MD from 7.3 (2.9) to 13.1 (3.6) (p =
      0.05) and LV from 31.0 (22.9) to 71.8 (24.1) (p = 0.017)). When comparing the
      mean retinal sensitivity in the area of the primary CNVM (including classic,
      occult, and haemorrhagic components), the results were analogous: in patients
      with a regression of the CNVM after irradiation the mean sensitivity remained
      almost unchanged. It was 10.3 (6.4) dB at baseline and 9.4 (7.3) dB at 12 months
      (p = 0.58). In five out of 11 patients (45%) with regression of the CNVM, the
      mean retinal sensitivity even improved by 2.0-5.0 dB in the area of the original
      lesion during follow up. Instead, in patients showing progression of the CNVM at
      12 months, there was a significant loss in mean retinal sensitivity--from 9.9
      (4.6) dB at baseline to 1.0 (1.1) dB at 12 months (p = 0.019). The mean retinal
      sensitivity in the area of the irradiated but clinically normal retina during
      follow up was not significantly altered (21.5 dB at baseline, 19.7 dB at 12
      months (p = 0.10)). CONCLUSIONS: Regression of subfoveal choroidal membranes in
      AMD after focal strontium irradiation is connected with stabilisation or even
      improvement of retinal sensitivity in central visual field measured by automated
      perimetry. Strontium plaque irradiation does not change the sensitivity in
      clinically normal paramacular retina during a 12 month follow up.

PMID- 9924369
TI  - RA/DA cumulative curve analysis of local and diffuse neuroretinal rim area damage
      in glaucoma patients.
AB  - AIM: To evaluate the validity of cumulative rim/disc area (RA/DA) curve analysis
      as a clinical tool for the identification of glaucoma induced optic disc
      pathology. METHODS: 71 normal and 83 glaucomatous eyes were evaluated from a
      series of 154 subjects recruited for this study. For each eye, the cumulative
      distribution of RA/DA was calculated from 36 equally spaced rim sectors of each
      optic disc obtained by the automatic evaluation of simultaneous videographics
      (Image-net X Rev.3/51b). To increase the sensitivity of this analysis in early
      glaucoma and in normal eyes, these cumulative curves were subsequently divided
      into two equal segments and the slopes of their respective regression lines
      compared. RESULTS: The median RA/DA value obtained from the 36 sectors was
      significantly different in glaucomatous eyes compared with normals (p < 0.001).
      Nevertheless, the curves (5th-95th percentile of the cumulative curves
      distribution) of early glaucomatous eyes fell within the normal range. When the
      cumulative curve of these marginal cases was then divided into two equal
      segments, the comparison of the slopes of the regression lines showed a
      significant difference (p < 0.05) in 100% of early glaucomatous eyes.
      Furthermore, normal eyes were shown to be true negatives in 93% of the cases in
      which no significant difference between the two slopes was observed. CONCLUSION:
      Analysis of the RA/DA cumulative curve from 36 sectors of the optic disc was a
      valid method for the identification of glaucomatous disc pathology; however, a
      further calculation of the slopes of the two RA/DA regression lines was needed to
      identify early glaucomatous damage.

PMID- 9924370
TI  - Development of a disease specific quality of life questionnaire for patients with
      Graves' ophthalmopathy: the GO-QOL.
AB  - AIM: To develop a reliable and valid disease specific quality of life
      questionnaire (the GO-QOL) for patients with Graves' ophthalmopathy (GO), that
      can be used to describe the health related quality of life and changes in health
      related quality of life over time as a consequence of disease and treatment.
      METHODS: 70 consecutive GO patients (age > 18 years) who were referred for the
      first time to the combined outpatient clinic of the orbital centre and the
      department of endocrinology completed the 16 questions of the GO-QOL. Additional
      information on general quality of life and disease characteristics was obtained.
      Construct validity and internal consistency of the disease specific questionnaire
      was determined, based on principal component analysis, Cronbach alphas and
      correlations with MOS-24, three subscales of the SIP, demographic, and clinical
      measures. RESULTS: The a priori expected subdivision of the questionnaire in two
      subscales, one measuring the consequences of double vision and decreased visual
      acuity on visual functioning, and one measuring the psychosocial consequences of
      a changed appearance, was confirmed in the principal component analysis. Both
      scales had a good reliability and high face validity. Correlations with other
      measures supported construct validity. Mean scores (range 0-100) were 54.7 (SD
      22.8) for visual functioning and 60.1 (24.8) for appearance (higher score =
      better health). CONCLUSION: The GO-QOL is a promising tool to measure disease
      specific aspects of quality of life in patients with GO and provides additional
      information to traditional physiological or biological measures of health status.

PMID- 9924371
TI  - Knowledge, attitudes, and self care practices associated with age related eye
      disease in Australia.
AB  - AIM: To determine the level of correct knowledge about common eye disease and
      attitudes towards blindness prevention and treatment, and how these factors
      influence self care practices in a population based sample. METHODS: A cluster
      random sample of the Victorian population was interviewed. The study population
      comprised residents aged 40 years of age or older living in five randomly
      selected Melbourne metropolitan suburbs and four randomly selected rural areas of
      Victoria. Questions were asked to ascertain each person's knowledge of common age
      related eye disease--that is, cataract, age related macular degeneration (AMD),
      and glaucoma. A subsample of the population was also asked questions to determine
      their attitudes to blindness prevention and treatment. All respondents were asked
      the year of their last visit to an eye practitioner. RESULTS: A total of 3184
      (89%) eligible residents were assessed. Sex (females), age (younger people),
      higher levels of education (secondary, trade, or tertiary education), recent
      visit to an eye practitioner (within the past 2 years) and English spoken at home
      appeared to be significant predictors of knowledge of common age related eye
      conditions. Younger people believed blindness prevention and blindness treatment
      were the highest priorities compared with other diseases; people who spoke
      English at home and people with knowledge of common age related eye disease also
      considered blindness treatment to be the highest priority compared with other
      diseases. People with a previous diagnosis of age related eye disease, older
      people, females, people with correct knowledge of common eye diseases, and those
      who spoke English at home were significantly more likely to be under eye care. No
      interaction was found between knowledge and positive attitudes to self care
      practices. CONCLUSION: These data show that there is a large gap in the public's
      knowledge and understanding of eye disease that will need to be understood for
      eye health promotion activities.

PMID- 9924372
TI  - Ultrasonic assessment of rhinostomy size following external
      dacryocystorhinostomy.
AB  - AIM: To assess the dimensions and patency of the surgical epithelial fistula
      after external dacryocystorhinostomy, using B mode ultrasonography to define the
      postoperative soft tissue anastomosis. METHODS: 12 patients undergoing 16
      external dacryocystorhinostomies, with the creation of large osteotomies, were
      included in a prospective study. The horizontal and vertical dimensions of the
      bone ostium was recorded during surgery and compared with the ultrasonographic
      dimensions of the soft tissue anastomosis at 1 day, 2 weeks, and 6 months after
      surgery. Functional patency was confirmed with dye testing and irrigation.
      RESULTS: Compared with an osteotomy of between 100 and 380 mm2 (mean 235 mm2),
      the soft tissue anastomosis on the day after surgery was, in all cases, markedly
      smaller (72-252 mm2; mean 144 mm2, or 61% of the bone window). The soft tissue
      anastomosis decreased to between 8 and 208 mm2 (mean 98 mm2; 68% of immediate
      postoperative value) at 2 weeks and 3-208 mm2 (mean 71 mm2; 49% of immediate
      postoperative value) at 6 months. 14 of the 16 (88%) dacryocystorhinostomies were
      functional at the end of the study, the two failures being associated with marked
      contracture of the soft tissue anastomosis; the outcome of surgery correlated
      significantly with the area of the anastomosis at 2 weeks (chi 2 = 16.3; p <
      0.01) and at 6 months (chi 2 = 16.0, p = 0.01). CONCLUSIONS: B mode
      ultrasonography provides a simple and effective method for assessing the size of
      the soft tissue anastomosis after external dacryocystorhinostomy and there is a
      significant reduction in size after surgery, to which the functional outcome of
      surgery appears related. As the initial soft tissue anastomosis cannot be larger
      than (and is, on average, about 60% of) the area of the osteotomy, this
      emphasises the paramount importance of a large rhinostomy to the success of
      lacrimal surgery.

PMID- 9924373
TI  - Anterior suspended flaps: a modified approach for external dacryocystorhinostomy.
AB  - BACKGROUND/AIMS: External dacryocystorhinostomy (DCR) is a reliable but difficult
      surgical technique for the treatment of any obstruction of the lacrimal drainage
      system lying distal to the internal opening of the common canaliculus. In this
      prospective study, a simplified external DCR procedure and the results obtained
      on a series of 45 consecutive patients, in which traditional external DCR was
      indicated, are described. METHODS: In this modified procedure only very large and
      mobile anterior flaps of the lacrimal sac and nasal mucosa are created. Thanks to
      the large size and the great motility the two flaps can be easily sutured. Two
      double armed 6/0 polyglycolic acid sutures are used to join the two flaps, to
      elevate them anteriorly in order to avoid adhesions with underlying tissues, and
      to approximate the deep planes of the wound. The mean operative time was
      measured. RESULTS: At the end of follow up period (mean 17 months, range 14-24
      months) all patients had no sign or symptoms of tearing and normal Jones I dye
      test. The mean operative time was 28.6 minutes (range 23-44 minutes). CONCLUSION:
      We believe that our modified technique can be used to simplify and speed up
      traditional external DCR without decreasing its well known reliability.

PMID- 9924374
TI  - Emmetropisation, axial length, and corneal topography in teenagers with Down's
      syndrome.
AB  - AIM: To study the refractive status and corneal topography in Down's syndrome.
      METHOD: A matched cohort subgroup of 50 individuals with Down's syndrome in the
      Manchester area aged 15-22 years was studied by refraction, corneal topography, A
      scan biometry, slit lamp examination, and orthoptic examination. RESULTS: (1) A
      linear relation was found between axial length and spherical equivalent
      refraction. There was no statistical relation between keratometry and the axial
      length. (2) 80% of the group had a hyperopic refraction (mean +2.46 D, range +0.5
      to +7.5 D); 18% were myopic (mean -2.75 D, range -0.5 to -8.0 D); and 2% were
      emmetropic (within plus or minus 0.5 D of zero). The overall mean spherical
      equivalent refraction was +1.43 (SD 2.86) D. 63% of eyes could see 6/12 or better
      and 66% of the individuals had a binocular vision of 6/12 or better. (3) Corneal
      topography was generally of a regular "bow tie" pattern, but there was a high
      incidence of oblique cylinders. Mean cylinder strength was 1.14 (1.15) D. (4) The
      prevalence of overt keratoconus was 2%. 6% had corneal topography with inferior
      steepening which may be a preclinical keratoconic process. CONCLUSIONS: In this
      cohort of late teenagers with Down's syndrome, emmetropisation has failed to
      occur in most individuals. In a similar aged group of non-disabled individuals
      one would expect about 83% emmetropic (plus or minus 0.25 D), 13% myopic, and 4%
      hyperopic. The wide spread of oblique cylinders and the small proportion of with
      the rule astigmatism is probably related to this failure of emmetropisation. The
      prevalence of 2% keratoconus in Down's syndrome compares with that found by other
      authors of between 5.5 and 15%. The 6% with inferior steepening on topography
      will be followed up over the next few years to see if there is any development of
      clinical keratoconus. Hence we will see if corneal topography is useful as a
      screening tool for preclinical keratoconus in this high risk group.

PMID- 9924375
TI  - Impairment of ocular surface epithelium barrier function in patients with atopic
      dermatitis.
AB  - AIMS: To assess the integrity of the ocular surface epithelium in patients with
      atopic dermatitis from the viewpoint of its barrier function. METHODS: 49
      patients with atopic dermatitis with blepharoconjunctivitis (ABC group), 27 age
      matched patients with seasonal or perennial allergic conjunctivitis (AC group),
      and 20 volunteers with normal healthy eyes (NH group) were assigned to this
      study. Ocular surface epithelium barrier function was evaluated by the
      fluorophotometric method using a slit lamp fluorophotometer. 3 microliters of
      0.5% sodium fluorescein was instilled into the conjunctival sac of the right eye
      and fluorescein uptake (ng/ml) 30 minutes later (20 minutes after eye washing)
      was measured in the central cornea and the temporal bulbar conjunctiva.
      Fluorophoto metric measurements performed were analysed in each group and
      compared between the groups. RESULTS: The ABC group showed significantly higher
      fluorescein uptake (mean 28.2 (SEM 3.3) ng/ml) in the cornea than the AC (11.4
      (2.2), p = 0.001) and NH groups (9.3 (2.1), p = 0.001). There was no significant
      difference between the AC and NH groups (p = 0.930). The ABC group also showed
      significantly higher fluorescein uptake in the bulbar conjunctiva (393.4 (54.0))
      than the AC (182.9 (24.6), p = 0.011) and NH groups (169.3 (29.1), p = 0.012).
      There was also no significant difference in fluorescein uptake between the AC
      group and the NH group (p = 0.987). CONCLUSION: This study suggested that ocular
      surface epithelium barrier function is impaired in patients with atopic
      dermatitis with blepharoconjunctivitis.

PMID- 9924376
TI  - Visual outcome and prognostic factors after magnetic extraction of posterior
      segment foreign bodies in 40 cases.
AB  - AIMS: To evaluate the clinical features as well as the visual and anatomical
      outcome in eyes with magnetic posterior segment foreign bodies, to identify
      prognostic factors after removal using an electromagnet. METHODS: The records of
      40 patients with posterior segment foreign bodies were retrospectively reviewed
      for 6 years (1989-94). Post-traumatic cataracts and secondary retinal detachments
      were treated using conventional surgical techniques. Pars plana vitrectomy was
      used only for late complications. The mean follow up was 30 months (6-71).
      Clinical factors were studied using univariate analysis. RESULTS: The most common
      findings before treatment of these 40 eyes were lens wound, hyphaema, vitreous
      haemorrhage, and retinal impairment. The foreign body was in the vitreous (85%)
      or minimally embedded in the retina (15%). Initial visual acuity was worse or
      equal to 20/40 in 70% of the cases. Subsequent to surgical treatment, a cataract
      was reported in 60% of the patients. Postoperative complications included retinal
      detachment (15%) and phthysis (5%). The prognosis was worse in cases with
      intraocular foreign body of largest diameter > or = 3 mm, an initial visual
      acuity less than 20/200, or the presence of post-traumatic retinal detachment.
      Presence of initial intravitreous haemorrhage, hyphaema, or intraocular tissue
      prolapse did not appear to affect the prognosis. CONCLUSION: The long term visual
      acuity results indicated that wound repair associated with conventional magnet
      extraction in an emergency is a viable treatment for posterior segment magnetic
      foreign bodies in this selected group. At the time of diagnosis, size of foreign
      body (< 3 mm) and initial visual acuity > or = 20/200 were predictors of good
      visual outcome after primary magnetic extraction.

PMID- 9924377
TI  - "Johnny Poppers": a cause of serious ocular injury.
AB  - AIMS/BACKGROUND: The causes of blunt ocular trauma are many and diverse. We
      present two cases of ocular injury caused by an unusual form of weapon called a
      "Johnny Popper". There follows a theoretical and experimental evaluation of the
      velocity of the projectiles fired by this device. METHODS: A Johnny Popper was
      constructed under expert guidance. The elastic properties of the device were
      measured and this allowed calculation of a theoretical exit velocity of the
      projectiles fired. The weapon was subsequently fired under test conditions which
      permitted the exit velocity of the projectiles fired to be measured directly.
      RESULTS: The theoretical velocity of the projectiles was calculated as 80 ms-1
      and the experimentally measured velocity was 57 ms-1. CONCLUSIONS: Johnny Poppers
      are a previously undescribed and unique form of home made weapon. They are
      intended for playful mischief, but have the potential to cause serious ocular
      trauma.

PMID- 9924378
TI  - Recombinant tissue plasminogen activator in cases with fibrin formation after
      cataract surgery: a prospective randomised multicentre study.
AB  - AIMS: This study investigated the effect of tissue plasminogen activator (tPA) in
      patients with severe intracameral fibrin after extracapsular cataract extraction
      or phacoemulsification with posterior chamber intraocular lens implantation.
      METHODS: A randomised prospective multicentre study was carried out in 86
      patients with intraocular fibrin formation 2-8 days after cataract surgery. While
      the first group (n = 41) received only anti-inflammatory drugs, a single anterior
      chamber injection of tPA (10 micrograms) as an additional treatment to the
      standard was given in the second group (n = 44). On days 1, 2, 14, and 90 after
      randomisation, the visual acuities, slit lamp findings, and intraocular pressures
      were documented in standardised protocols. Efficacy of treatment was judged by
      the rate of fibrinolysis (primary objective), the frequency of synechiae, and
      central capsular fibrosis (secondary objectives). RESULTS: The incidence and
      quantity of intraocular fibrin were significantly lower in the patients treated
      with tPA than in the control group (p < 0.05). The frequencies of synechiae were
      reduced by tPA injection. The capsule fibrosis noted after 3 months was
      significantly lower in the tPA group (p = 0.027). No ocular side effects were
      noted after the tPA injections. CONCLUSIONS: Lysis of postcataract fibrin
      formation is accelerated and increased by a single intracameral injection of 10
      micrograms tPA in addition to standard anti-inflammatory treatment. The findings
      suggest that the tPA injection reduces posterior capsule fibrosis, which still
      has to be addressed in larger study populations and with a long term follow up.

PMID- 9924379
TI  - Suramin inhibits wound healing following filtering procedures for glaucoma.
AB  - BACKGROUND: Trabeculectomies are the most frequently performed procedures in
      surgically treating eyes with glaucoma. Failures are caused by fibrosis in the
      external ostium of the filtering procedure. In order to inhibit the fibrotic
      wound healing reaction, a new pharmacological approach using suramin, which
      inhibits a variety of important growth factors was used. METHODS: Pigmented
      rabbits were used and filtering procedures performed. Suramin was applied with
      concentrations ranging from 10 mg/ml to 333 mg/ml once during surgery and four
      times following surgery. The success of the filtering procedure was assessed by
      intraocular pressure measurements. To evaluate possible intraocular toxic
      effects, treated eyes were histopathologically evaluated after 4 weeks, and the
      ciliary body adjacent to the site of application was examined using electron
      microscopy. RESULTS: With concentrations of suramin of 200 mg/ml and 333 mg/ml,
      the trabeculectomies were patent longer than in the controls and in eyes operated
      with mitomycin C, which currently is the most frequently used antiproliferative
      drug to enhance the outcome of surgery in humans. No severe toxic effects to the
      ciliary epithelium were seen in suramin treated eyes. CONCLUSIONS: This study
      demonstrates for the first time the efficiency of a substance that broadly
      inhibits the action of growth factors on target cells in the setting of ocular
      wound healing. In this in vivo model, suramin has been shown to be highly
      effective in preventing scarring and in having fewer toxic side effects than
      usually used antimetabolites. These results therefore may suggest a new approach
      to the surgical treatment of glaucoma.

PMID- 9924380
TI  - Relation between pressure determined by ophthalmodynamometry and aortic pressure
      in the dog.
AB  - AIMS: Ophthalmodynamometry has been used extensively since the last century;
      however, controversy surrounds what it actually measures. This study was set up
      to determine the relation between ophthalmodynamometric (ODP) and systemic blood
      pressures. METHODS: Aortic pressure was continuously monitored and altered by
      phlebotomy in six anaesthetised dogs, while ophthalmodynamometry was performed,
      by directly altering intraocular pressure. Maxillary artery pressure was
      monitored in two animals. All pressure transducers were zeroed at eye level.
      RESULTS: Mean ODP was 96.6% (1.6%) (95% confidence interval, n = 49) of aortic
      pressure. Mean maxillary artery pressure was 95.7% (5.5%) (95% CI, n = 16) of
      aortic pressure. ODP was 1.9 (0.6) mm Hg (95% CI, n = 33) higher than maxillary
      artery pressures. CONCLUSION: ODP was only slightly below aortic pressure and not
      significantly different from maxillary artery pressure, the analogue of the
      internal carotid artery in humans. These results also suggest a retinal artery
      collapse pressure of at least 1.9 mm Hg.

PMID- 9924381
TI  - Role of the endothelium in modulating functional responses of isolated bovine
      anterior ciliary arteries to vasoconstrictor agonists.
AB  - BACKGROUND/AIMS: Endothelium dependent vasodilatation is an important regulator
      of blood flow to the eye but its role has not been investigated in vessels
      supplying the ciliary body. This study assessed the role of the endothelium in
      modulating vasoconstrictor responses of the intraocular bovine anterior ciliary
      artery. METHODS: Bovine anterior ciliary arteries (n = 33) were mounted in a
      myograph, containing physiological salt solution at 37 degrees C, for isometric
      force measurement. Cumulative concentration-response curves were obtained to the
      constrictor agonists 5-hydroxytryptamine (5-HT), noradrenaline, phenylephrine,
      prostaglandin, F2 alpha, endothelin-1, and KCl in both endothelium intact and
      denuded arteries. RESULTS: All vasoconstrictors produced sustained contractile
      responses which were unaffected by the removal of the endothelium. Responses to 5
      HT were also unaffected by inhibition of nitric oxide synthase. CONCLUSION: These
      results indicate that neither agonist stimulated nor basal release of nitric
      oxide from the endothelium modulates responses to vasoconstrictor agonists in the
      isolated bovine anterior ciliary artery when measured in a no flow isometric
      system.

PMID- 9924382
TI  - Brain natriuretic peptide: identification of a second natriuretic peptide in
      human aqueous humour.
AB  - AIMS/BACKGROUND: To measure aqueous humour levels of brain natriuretic peptide
      (BNP) and atrial natriuretic peptide (ANP) in humans. To compare peptide levels
      in glaucomatous and control eyes to test the hypothesis that these peptides are
      increased in glaucoma. BNP and ANP are cyclic endopeptides whose principal
      biological effects are natriuresis and vasodilatation. Experimental glaucoma in
      animal models results in elevated aqueous ANP. Intravenous ANP administration in
      both animals and humans causes lowering of intraocular pressure (IOP). There are
      equivocal data to support a role for ANP in IOP regulation in human eyes. There
      are as yet no published data on BNP in human aqueous humour. METHOD: This was a
      case-control study. Cases were primary open angle, pseudoexfoliation, and mixed
      mechanism glaucoma eyes undergoing trabeculectomy. Controls were cataract
      extraction eyes. There were 47 trabeculectomy eyes (44 patients) and 47 cataract
      extraction eyes (46 patients) matched for age, sex, race, systemic medications,
      and type of anaesthetic. 100-200 microliters of aqueous humour were aspirated by
      paracentesis as the first step in the surgical procedure. Peptide levels were
      later measured by radioimmunoassay. RESULTS: The presence of BNP and ANP in human
      aqueous humour was confirmed. BNP was present in higher concentrations than ANP.
      BNP levels tended to be greater in control eyes--glaucoma median 56.5 (range 0
      3526.5) pg/ml versus control median 65.16 (range 0-1788) pg/ml (Wilcoxon signed
      rank test p = 0.78). ANP levels tended to be greater in glaucoma eyes than in
      controls: glaucoma median 3 (range 0-68.5) pg/ml versus control median 0 (range 0
      60) pg/ml (Wilcoxon signed rank test p = 0.82). ANP and BNP were log linearly
      related in both groups (r glaucoma group = 0.961, r control group = 0.894).
      CONCLUSION: This is the first report of BNP and ANP in human aqueous humour.
      Peptide levels did not differ significantly between glaucoma and cataract
      extraction eyes. A linear relation between log BNP and ANP was found. Further
      studies are required to clarify the role of these peptides in aqueous humour
      production and IOP regulation.

PMID- 9924384
TI  - Retinopathy associated with pancreatitis in a child with maple syrup urine
      disease.

PMID- 9924383
TI  - Normal tension glaucoma--a practical approach.

PMID- 9924386
TI  - Retinal haemorrhage caused by "ecstasy".

PMID- 9924385
TI  - Immediate postoperative objective refraction as an indication to final refraction
      in phacoemulsification surgery.

PMID- 9924387
TI  - Latanoprost and cystoid macular oedema in a pseudophake.

PMID- 9924389
TI  - Do all patients with CMV retinitis require life long anti-CMV therapy?

PMID- 9924388
TI  - Factor V Leiden mutation in association with idiopathic intracranial
      hypertension.

PMID- 9924391
TI  - Successful penetrating keratoplasty in an infant after extended storage of
      infantile donor cornea.

PMID- 9924390
TI  - Spontaneous and sustained resolution of CMV retinitis in patients receiving
      highly active antiretroviral therapy.

PMID- 9924392
TI  - Choroidal melanoma in a patient with retinitis pigmentosa and Usher's syndrome.

PMID- 9924393
TI  - Diagnosis of activated protein C resistance in retinal vein occlusion.

PMID- 9924394
TI  - Peripapillary circle of Zinn-Haller.

PMID- 9924395
TI  - Effectiveness of occlusion therapy in ametropic amblyopia.

PMID- 9924396
TI  - High prevalence of recurrent symptoms following uncomplicated traumatic corneal
      abrasion.

PMID- 9924397
TI  - Cluster of four cases of inadvertent injury to the globe secondary to peribulbar
      anaesthesia.

PMID- 9924398
TI  - Telemedicine and computers in diabetic retinopathy screening.

PMID- 9924399
TI  - The bilobed island flap in nasal ala reconstruction.
AB  - A bilobed island flap with an extended subcutaneous pedicle including part of the
      transverse portion of the elevator muscle of the nasal ala is described. This
      flap was employed for nasal ala reconstruction in 21 patients following excision
      of malignancy. The series includes 12 females and 9 males ranging in age from 25
      to 83 years. In 19 patients, the reconstruction spared the mucosa layer and in
      two a skin graft was used under the flap to reconstruct the lining. The flap was
      viable in all cases and the aesthetic outcome satisfactory. The rotation fold dog
      ear is eliminated. In planning the BIF the length of its lobes (proximal and
      distal), should be equal to the defect; the width of the proximal lobe, compared
      to the defect, and the distal lobe compared to the proximal lobe should be
      progressively narrower.

PMID- 9924400
TI  - Facial contour reconstruction in localised lipodystrophy using free radial
      forearm adipofascial flaps.
AB  - Unilateral facial contour deformities in two patients with localised
      lipodystrophies were reconstructed with free radial forearm adipofascial flaps.
      At follow-up of 5 and 4 years there is no significant downward gravitation, and
      the flaps have maintained their integrity and bulk. Both the patients have had
      significant improvement in their self-consciousness of appearance. Since the
      donor site was closed primarily, a linear forearm scar remains the only donor
      site morbidity.

PMID- 9924401
TI  - Reconstruction of posterior mandibular defects with soft tissue using the rectus
      abdominis free flap.
AB  - Immediate reconstruction of posterior mandibular composite defects by replacement
      with vascularised bone is ideal in principle, but may have excessive morbidity
      for certain patients who, because of poor general health or a poor tumour
      prognosis, are not good candidates for a complex surgical procedure. Also, if the
      temporomandibular joint (TMJ) is missing, the continuity of the entire mandible
      cannot be restored without either reconstructing the TMJ or resorting to a
      prosthesis. For such patients, reconstruction of the posterior defect without
      bone using a rectus abdominis free flap or other soft-tissue flap may be a good
      alternative. A series of 21 patients with posterior mandibular defects underwent
      this type of reconstruction. The patients reconstructed only with soft tissue
      were found to have a reasonable cosmetic appearance, and speech and swallowing
      function were very acceptable. For posterior mandibular defects that include a
      missing condyle this approach is an acceptable alternative, especially for
      patients who are poor candidates for more complex surgical procedures.

PMID- 9924402
TI  - Alterations in nasal sensibility following open rhinoplasty.
AB  - Alterations of nasal sensibility following open rhinoplasty were studied both
      subjectively and objectively. In a prospective study, 25 patients were included.
      All patients underwent open rhinoplasty using a middle columellar incision.
      Subjective questioning and objective testing of nasal sensibility using the
      Semmes-Weinstein monofilaments were obtained preoperatively and both 3 weeks and
      1 year after surgery. The match-paired Student's t-test was used for statistical
      analysis. At 3 weeks after surgery, there was subjective and significant
      objective alteration of sensibility in the area of skin supplied by the external
      nasal nerve (nasal tip and adjacent upper columella). This altered sensibility,
      however, recovered by 1 year after surgery. The recovery was thought to be due
      either to recovery of the external nasal nerve itself, or to collateral sprouting
      from the nerves supplying the adjacent areas of nasal skin.

PMID- 9924403
TI  - Primary repair of an incomplete unilateral cleft lip: avoiding an elongated lip
      and achieving a straight suture line.
AB  - The methods designed for the repair of a complete cleft lip should not be used to
      repair an incomplete cleft lip. This results too often in the postoperative
      drooping of the white lip on the affected side because in most incomplete cleft
      lips there is more tissue on the cleft side than in complete cleft lip. We
      present and discuss the refinements we made in our original technique for
      complete cleft lip in order to adapt it to incomplete cleft lip repair. The skin
      design at the white skin roll follows Cronin's method with an incision
      perpendicular to the vermilion border. The suture that pulls the edges of the
      angular incisions together pushes on the white skin roll caudally. This ensures
      that the peak of the Cupid's bow on the cleft side does not droop
      postoperatively. It also ensures that it does not take on an acute angle and that
      the vermilion border will be a continuous line without a break. We do not create
      a triangular flap at the vermilion border, but we raise a triangular flap at the
      alar base on the cleft side and advance it to the bottom of the columella. This
      creates the nostril sill and corrects the flared alar base. The resulting suture
      line is completely straight and runs along the philtral column. In this way, the
      postoperative elongation of the white lip on the cleft side can be prevented.

PMID- 9924404
TI  - Chronic non-specific parotid sialadenitis.
AB  - Chronic non-specific sialadenitis of the parotid gland is an insidious
      inflammatory disorder which is characterised by intermittent, often painful,
      swelling of the gland. The disease tends to progress and may lead to the
      formation of a fibrous mass. The purpose of this paper is to review our
      experience in the surgical management of patients with chronic non-specific
      parotid sialadenitis. In a consecutive series of 100 patients treated for benign
      parotid disease, 19 were found to have chronic non-specific sialadenitis; 10 were
      male and 9 female. Mean age was 46 years and the mean duration of symptoms was
      4.6 years. Sialography was performed in two-thirds of the patients and 17
      patients were treated by superficial parotidectomy. Thirteen patients developed
      temporary facial nerve weakness and three Frey's syndrome. Three patients
      complained of temporary paraesthesia of the cheek, and two developed painful
      neuroma of the greater auricular nerve. Although there were two cases of
      infection of the parotid duct remnant, no recurrence of deep lobe sialadenitis or
      fistula formation was noted. Histologically, 3 lesions showed mild chronic
      sialadenitis, the rest had widespread involvement of the gland, and prolonged
      duration of symptoms was associated with extensive and severe involvement of the
      gland. Superficial parotidectomy has a very high success rate, with minimal long
      term complications, and should be offered early in established cases, to reduce
      unnecessary morbidity.

PMID- 9924406
TI  - An investigation into changes in lung function and the subjective medical
      benefits from breast reduction surgery.
AB  - The aim of this study was to assess the respiratory changes following reduction
      mammaplasty in women presenting for elective surgery; In addition, to assess
      whether these changes might be related to any symptomatic improvement. This was a
      prospective study examining women attending for breast reduction surgery over a 3
      month period. Preoperative pulmonary function studies (PFTs) and a symptom
      questionnaire were completed before operation. These were repeated 6-8 weeks
      after surgery. Pulmonary function testing was carried out in all cases by the
      same operator. The study was carried out within a sub regional centre for plastic
      and reconstructive surgery. Local Ethics committee approval was obtained.
      Nineteen healthy women mean age 34.9 years and with a mean Body Mass Index of
      27.62 were recruited. The mean weight of excised breast tissue was 1546 g. All
      preoperative pulmonary function tests were within normal limits. Six of the women
      smoked, none changed their smoking habits over the course of this study. Changes
      in pulmonary function studies were analysed using the paired t-test. A 'P' value
      of < 0.05 was considered to be significant. Seventeen women had a post operative
      improvement in PFTs. Statistically significant improvements were obtained for
      changes in peak expiratory flow rate (PEFR, P = 0.005) and peak inspiratory flow
      rate (PIFR, P < 0.0001). The 'P' values for changes in FEV1 (forced expired
      volume in 1 second) and FEV1/FVC (forced vital capacity) did not reach
      significance, whilst the 'P' value for the change in FVC was statistically
      significant (P = 0.01), although the actual mean change was small (0.07 litres).
      The study sample was too small to relate these changes to mass of excised tissue
      or BMI. All women taking part claimed an increased confidence and a cessation in
      analgesic use. Other reported benefits included an improved exercise tolerance
      (12/19), reduced sleep disturbance (4/19) and reduced breathing difficulties
      (1/19).

PMID- 9924405
TI  - Stereolithographic (SL) biomodelling in craniofacial surgery.
AB  - BACKGROUND: Stereolithographic (SL) biomodelling allows 3D CT to be used to
      generate solid plastic replicas of anatomical structures (biomodels). Case
      reports in the literature suggest that such biomodels may have a use in
      craniofacial surgery but no large series or assessment of utility has been
      reported. A prospective trial to assess the utility of biomodelling in
      craniofacial surgery has been performed. METHODS: Forty patients with complex
      craniofacial abnormalities were selected and 3D CT scanning performed. The data
      of interest was used to guide a laser to selectively polymerise photosensitive
      resin to manufacture SL biomodels. The biomodels were used for patient education,
      diagnosis and operative planning. An assessment protocol was designed to test the
      hypothesis that biomodels in addition to standard imaging had greater utility in
      the surgery performed than the standard imaging alone. RESULTS: Anecdotally
      surgeons found biomodelling useful in 40 complex craniofacial operations. The
      formal assessment of the first 10 cases suggested biomodels improved operative
      planning (image 76%, image with biomodel 97%, P < 0.01) and diagnosis (image
      82.5%, image with biomodel 99.25%, P < 0.01). Surgeons estimated that the use of
      biomodels had reduced operating time by a mean of 16% and were cost effective at
      a mean price of $1100 AUS. CONCLUSION: Biomodelling was reported as an intuitive,
      user-friendly technology that facilitated diagnosis, operative planning and
      communication between colleagues and patients. Limitations of the technology were
      manufacturing time and cost.

PMID- 9924407
TI  - Bilateral breast reconstruction in very thin patients with extended free TRAM
      flaps.
AB  - A lateral extension of the free TRAM flap design is described for use in
      unusually thin patients who desire bilateral autologous tissue breast
      reconstruction. Because of the exceptionally good blood supply to the free TRAM
      flap, the lateral extensions are viable even when the flap is folded double to
      increase its thickness and projection. To increase the volume of the
      reconstructed breast, the flaps can be extended as far laterally as the surface
      of the operating table will permit. With this approach, bilateral TRAM flap
      breast reconstruction is possible even for extremely thin patients.

PMID- 9924408
TI  - Umbilicosculpture: a concept revisited.
AB  - After birth the umbilicus is the only naturally formed visible scar on the body.
      To reconstruct a neo-umbilicus following abdominoplasty various local
      interposition flaps have been described to circumvent a circular scar contracture
      and to recreate a superior hood. The additional scarring with these techniques
      can give an operated look to the neo-umbilicus. The importance of gravity in the
      formation of a superior hood is highlighted and the issue of circular scar
      contractures is addressed. Emphasis is placed on sculpturing the peri-umbilical
      fat to enhance contour and on placing the circular scar deep in the neo
      umbilicus.

PMID- 9924409
TI  - An investigation into the role of waterproofing in a two-stage hypospadias
      repair.
AB  - In our unit a two-stage procedure, using a full thickness preputial graft, has
      been adopted as the method of choice for the repair of hypospadias proximal to
      the coronal sulcus. In 1993 an audit was undertaken to establish our complication
      rate for this procedure. Twenty-two consecutive patients who completed a two
      stage repair between January 1988 and December 1993 were studied. An unacceptably
      high fistula rate was identified (63%, 14/22 cases). Consequently our technique
      was modified by transposing a vascularised flap of preputial areolar tissue over
      the urethral suture line, at the time of urethroplasty. A second group of 22
      consecutive patients, operated upon between January 1994 and July 1997, were
      subsequently investigated and a dramatic improvement in the fistula rate was
      demonstrated (4.5%, 1/22 cases). These cases represent a subgroup of almost 200
      cases, which the senior author has managed over the last 10 years. The senior
      author undertook or supervised the surgery in all 44 cases, which were the focus
      of this study, and the introduction of a waterproofing layer represents the only
      change in technique.

PMID- 9924410
TI  - Consenting and consulting for cosmetic surgery.

PMID- 9924411
TI  - Pharmacological enhancement of cutaneous flap survival with topical dimethyl
      sulphoxide and hydrogen peroxide.
AB  - The present study was designed to investigate, in a rabbit model, the value of
      topical application of a solution of hydrogen peroxide (H2O2) 8% + dimethyl
      sulphoxide (DMSO) 50% in order to reduce ischaemic failure in random skin flaps.
      Two parallel, cephalad-based para-midline random cutaneous flap (10 cm x 2.5 cm)
      were elevated and resutured in place on the dorsum of 40 New Zealand rabbits. The
      80 flaps thus obtained were then randomly divided into one control group and
      three experimental groups of 20 flaps each. Flaps from the control group (Group
      A) were topically treated with saline, while flaps from experimental Group B were
      treated with H2O2 8%, flaps from experimental Group C with DMSO 50%, and flaps
      from experimental Group D with a solution of 50% DMSO + 8% H2O2. Each solution
      was topically applied to the flaps, 20 ml three times a day for 7 days, starting
      in the immediate postoperative period. Transcutaneous oxygen tension (PtcO2)
      measurements were carried out in all flaps 72 h after flap elevation. The
      percentage of surviving skin area of each flap was determined by planimetry 7
      days after flap elevation. The mean surviving area of the Group A (control) flaps
      was 71%, the mean surviving area of the Group B (H2O2-treated) flaps was 72%, the
      mean surviving area of the Group C (DMSO-treated) flaps was 76%, and that of the
      Group D (DMSO+H2O2-treated) flaps was 92%. While no statistically significant
      differences were found between the survival rates of both the flaps treated with
      H2O2 or DMSO alone and that of the control group, the mean surviving rate of the
      DMSO+H2O2 treated flaps (+20%) was statistically higher than that of the control
      flaps. Similarly, a statistically significant difference has been found between
      the mean PtcO2 values of the DMSO+H2O2 flaps and those of the other three groups
      of flaps.

PMID- 9924412
TI  - Axonal regeneration through muscle autografts submitted to local anaesthetic
      pretreatment.
AB  - Freeze-thawed muscle grafts (FTMG) have been used as an alternative to nerve
      grafts for the reconstruction of peripheral nerve defects, although their use has
      some disadvantages. For instance, FTMG may fragment easily after freeze-thawing,
      a fact impairing their use for surgery. In this study we describe a method to
      obtain muscle autografts based on the myotoxic properties of local anaesthetics.
      Fifteen adult rats had their left tibialis anterior muscles injected
      transcutaneously with 0.3 ml of 2% lidocaine hydrochloride. Twenty-four hours
      later the injected muscle was removed and a lidocaine muscle graft (LMG) was
      obtained by trimming the muscle to a rectangular block of approximately 1.0 cm in
      length. The left sciatic nerve was exposed in the mid-thigh region and a segment
      removed so that a final 1.0 cm-long gap was produced. The LMG was coaxially
      autografted to the epineurium between the proximal and distal nerve stumps. In
      another 15 rats, the sciatic nerve gap was repaired with FTMG obtained from the
      tibialis anterior muscle. Surgical procedures were similar in both groups. Axonal
      regeneration and muscle reinnervation were studied quantitatively and
      ultrastructurally 60 days after the insertion of LMG and FTMG. The results showed
      that axonal regeneration with the LMG was qualitatively similar to that observed
      with the FTMG, with no significant differences between groups. We conclude that
      LMG was a successful muscle graft and a suitable alternative to other denaturing
      methods, without the disadvantages of FTMG.

PMID- 9924413
TI  - Use of a regulating flap in the treatment of a large arteriovenous malformation
      of the scalp.
AB  - A patient presented with a large arteriovenous malformation (AVM) of the scalp.
      Afferent arterial embolisation followed by repeated surgical partial excision did
      not prevent recurrence and haemorrhage. The malformation was controlled with a
      latissimus dorsi muscle free flap which was positioned on the malformation. Five
      years later, haemorrhages did not recur and the nidus has disappeared on the
      angiogram. The positioning of a well-vascularised free tissue transfer provided
      long-term palliation and the authors believe that this flap acted as a
      'regulating flap'. As repeated surgery of these large AVMs always leads to rapid
      recurrences, the authors recommend treating large AVMs directly with a regulating
      flap when total excision is not possible.

PMID- 9924414
TI  - Radial artery aneurysm in a case of neurofibromatosis.
AB  - Vasculopathy as part of the syndrome of neurofibromatosis is well recognised,
      although rarely identified clinically. A recent report describes a case with
      rupture of an aneurysm of the superficial femoral artery. We present a case of
      radial artery aneurysm, a previously unreported complication of neurofibromatosis
      affecting the upper limb.

PMID- 9924415
TI  - Modified adjustable technique to anchor the levator muscle to the flap used in
      total upper eyelid reconstruction.
AB  - Total, full thickness loss of the upper eyelid due to trauma, was reconstructed
      using the Mustarde total upper lid reconstruction method. The immobile flap was
      then anchored to the avulsed levator muscle at a second stage, using the
      technique described by Collin and O'Donnell for the correction of eyelid ptosis.
      We modified the technique by using two rows of anchor sutures instead of one and
      found it effective in raising the reconstructed eyelid in the traumatic case
      presented.

PMID- 9924416
TI  - Problems encountered in a questionnaire-based study intended to investigate the
      use of prophylactic antibiotics by plastic surgeons in the UK.

PMID- 9924417
TI  - Adaptation to the loss of the stereoscopic image in microsurgery.

PMID- 9924418
TI  - Successful treatment of a giant congenital melanocytic naevus with high-energy
      pulsed CO2 laser.

PMID- 9924419
TI  - Familial multiple glomus tumours: differential diagnosis and relation to carotid
      body/glomus jugulare tumours.

PMID- 9924420
TI  - The use of scalp flap as graft donor area.

PMID- 9924421
TI  - Naming of parts: a presentation of facial surface anatomical terms.

PMID- 9924422
TI  - Closure of the skin defect overlying infected non-union by skin traction.

PMID- 9924423
TI  - Pressure sores in pregnancy.

PMID- 9924424
TI  - The origin of gut and pancreatic neuroendocrine (APUD) cells--the last word?
AB  - The evidence that gut and pancreatic endocrine cells are not derivatives of the
      neural crest is overwhelming: yet this conclusion is still not universally
      accepted. In this editorial attention is drawn to the body of experimental
      evidence which points conclusively to gut and pancreatic endocrine cells arising
      from endoderm, not the neural crest, the neurectoderm or neuroendocrine
      programmed epiblast.

PMID- 9924425
TI  - Silver development in microscopy and bioanalysis: past and present.
AB  - With the experience accumulated from more than a century of silver applications
      in biology and medicine, physical development has become a powerful bioanalytical
      tool for marker amplification in blotting procedures, in situ hybridization,
      immunocytochemistry, histochemistry, and cytochemistry. Early, empirical
      techniques of silver impregnation followed by development in a reducing solution
      (chemical developer), or a solution which contained both silver reducers and
      silver salts (physical developer) were often capricious and suffered from
      unwanted silver precipitation caused by light and self-nucleation. To accommodate
      the modern demand for accurate physical development, various strategies have been
      devised to counter these problems. One approach has been to introduce organic
      colloids into the developer to keep the silver ions and reducer molecules apart,
      whilst excluding light by using a dark-room or by covering the solution. Albumen,
      gelatin, and complex polysaccharides have all been tested, but gum arabic is
      preferred. In addition, further control can be achieved by slowing down the rate
      of development with low pH and by changing from silver nitrate to silver lactate,
      which dissociates more slowly. Effective colloid protection in a physical
      developer is also provided by the inclusion of tungsten salts which can delay
      light-catalysed silver reduction and keep the developer clear for many minutes.
      The same result has been achieved by complexing the silver salt in the physical
      developer with very large organic molecules, restricting ionization. 'Light
      insensitive' commercial designer products have resulted. Probably no single
      formulation can satisfy all conditions of use, but with increased understanding
      of the mechanisms of physical developers a more flexible, user-friendly approach
      is anticipated.

PMID- 9924426
TI  - Expression of co-stimulatory factor B7-2 on the intrahepatic bile ducts in
      primary biliary cirrhosis and primary sclerosing cholangitis: an
      immunohistochemical study.
AB  - Co-stimulatory factors B7-1 (CD80) and B7-2 (CD86) and their ligands, including
      CD28, are important for the efficient presentation and persistence of an antigen
      specific immune reaction. Hitherto, there has been a paucity of data on the roles
      of such co-stimulatory factors in immune-mediated biliary diseases. In this
      investigation, the hepatic immunohistochemical expression of B7-1 and B7-2 has
      been studied, with emphasis on intrahepatic biliary epithelia, using wedge
      biopsies from 22 patients with primary biliary cirrhosis (PBC), seven with
      primary sclerosing cholagitis (PSC), and, as controls, eight cases of
      extrahepatic biliary obstruction, eight of chronic viral hepatitis C, and three
      histologically normal livers. In 10/22 (45 per cent) patients with PBC and 3/7
      (43 per cent) patients with PSC, B7-2, but not B7-1, was expressed on the
      epithelial cells of small intrahepatic bile ducts and bile ductules. This
      expression was manifest as diffuse but variable cytoplasmic staining. Such B7-2
      positive bile ducts were not seen in controls. Positive staining was found only
      in the early stage of PBC and PSC. In PBC and PSC, almost all lymphocytes in the
      portal tracts, including those around the damaged bile ducts, were positive for
      CD28, a ligand of B7-2. These results suggest that B7-2 expression on biliary
      epithelial cells is involved in antigen presentation and perhaps in bile duct
      destruction in PSC and PBC.

PMID- 9924427
TI  - Frequent p53 gene mutations in serrated adenomas of the colorectum.
AB  - Serrated adenoma has been recently proposed as a distinct histological lesion of
      the colorectum. This study examined p53 immunoreactivity, mutations of exons 5-8
      of the p53 gene, codon 12 of the Ki-ras gene by PCR-SSCP analyses, and
      microsatellite instability in 19 serrated adenomas, ten adenocarcinomas in/with
      serrated adenomas, 23 hyperplastic nodules, four hyperplastic polyps and 29
      tubular adenomas of the colorectum. Eleven of 11 (100 per cent) serrated adenomas
      had p53 immunoreactivity and all six (100 per cent) adenocacinomas in/with
      serrated adenomas exhibited moderate to severe p53 immunoreactivity. It was
      confirmed that 9 of 19 (47 per cent) serrated adenomas and 5 of 10 (50 per cent)
      adenocarcinomas in/with serrated adenomas harboured p53 gene mutations. On the
      other hand, no p53 gene mutation was detected in the other colorectal lesions.
      Meanwhile, 11 (58 per cent) serrated adenomas and six (60 per cent)
      adenocarcinomas in/with serrated adenomas had Ki-ras gene mutations, as also did
      9 of 23 (39 per cent) hyperplastic nodules, 3 of 4 (75 per cent) hyperplastic
      polyps, and 12 of 29 (41 per cent) tubular adenomas. Microsatellite instability
      was detected in one (5 per cent) serrated adenoma and one (10 per cent)
      adenocarcinoma in a serrated adenoma. The other lesions did not show
      microsatellite instability. Serrated adenomas had significantly frequent p53 gene
      mutations compared with hyperplastic lesions or tubular adenomas (p < 0.005). On
      the other hand, they did not exhibit significant differences in mutations of the
      Ki-ras gene or in microsatellite instability. Genetic changes were then examined
      in small parts of serrated adenomas, such as the upper or lower parts of crypts,
      to determine the extent of gene mutations by using a microdissection technique.
      Exon 15 of the APC gene and the DCC gene, in addition to the p53 and Ki-ras genes
      and microsatellite instability, were analysed. Identical mutations of the p53
      gene were found in both invasive adenocarcinomas and adjacent serrated adenomas
      by direct sequencing, suggesting single clonal origins for those lesions.
      Mutations of the APC gene and microsatellite instability were heterogeneous in
      some lesions. No loss of heterozygosity (LOH) of the DCC gene was found. These
      findings suggest that mutations of the p53 gene are the most characteristic
      genetic alterations in serrated adenomas, as a relatively early event in a
      multistep carcinogenic pathway of this type of colorectal lesion, that might be
      distinct from the ordinary adenoma-carcinoma sequence or from carcinogenesis via
      mutations of mismatch repair genes.

PMID- 9924428
TI  - Co-expression of CD79a (JCB117) and CD3 by lymphoblastic lymphoma.
AB  - Acute lymphoblastic leukaemia/lymphoma is a malignant disorder derived from the
      clonal proliferation of lymphoid precursor cells. Whether the tumour cells are of
      B- or T-cell type is an important criterion for prognosis which has not been
      available previously to pathologists, due to the lack of a reliable early B-cell
      marker functioning on routinely processed material. This has changed with the
      production of monoclonal antibodies against the B-cell signalling molecule CD79a.
      CD79a is expressed on normal and neoplastic B cells from the early stages of B
      cell maturation and has been considered to be B-cell-specific. Currently
      available antibodies against CD79a, in particular JCB117, allow the
      identification of B cells, and hence B lymphoblastic disease, in paraffin
      embedded material. In this study, the expression of CD79a (JCB117) and CD3 has
      been investigated in 149 cases of T and 68 cases of B lymphoblastic
      leukaemia/lymphoma. For the first time, co-expression of CD79a (JCB117) and CD3
      is reported in 10 per cent of cases of T lymphoblastic leukaemia/lymphoma. This
      finding raises questions about the co-expression of T- and B-cell markers in the
      development of lymphocytes, benign as well as malignant, and alerts pathologists
      to a potential problem in diagnosis.

PMID- 9924429
TI  - Collagenase-3 expression is associated with advanced local invasion in human
      squamous cell carcinomas of the larynx.
AB  - Collagenase-3 (MMP-13) is a matrix metalloproteinase recently identified on the
      basis of differential expression in normal breast tissues and in breast
      carcinoma. To date, collagenase-3 expression has been reported only in breast
      carcinomas and in articular cartilage of arthritic patients; the presence and
      possible implication of this enzyme in the progression of other malignant tumours
      are unknown. In this study collagenase-3 mRNA expression has been analysed by
      northern blot in a series of 35 matched squamous cell carcinomas of the larynx
      and the corresponding adjacent non-neoplastic tissues. In addition, mRNA
      expression of membrane type 1-matrix metalloproteinase (MT1-MMP) and gelatinase
      A, two matrix metalloproteinases which have the ability to activate collagenase-3
      in vitro, was also examined in the same cases. No collagenase-3 expression was
      detected in any of the 35 normal mucosae, but collagenase-3 mRNA was observed in
      20 of the 35 carcinomas (57 per cent). Western blot analysis revealed the
      presence of collagenase-3 protein in those carcinomas with high levels of mRNA
      expression, whereas no protein was detected in the carcinomas with negative mRNA
      expression, or in any of the normal tissues. The protein was localized
      predominantly in tumour epithelial cells. Collagenase-3 expression correlated
      significantly with better histological differentiation of the tumours (p =
      0.026), as well as with advanced local invasion (p = 0.026). Collagenase-3
      upregulation was also significantly associated with MT1-MMP and gelatinase A
      overexpression. These findings suggest that collagenase-3 expression may
      contribute to the progression of a significant subset of squamous cell carcinomas
      of the larynx and that its coordinate overexpression with MT1-MMP and gelatinase
      A may have a cooperative effect in the progression of the tumours.

PMID- 9924431
TI  - Expression of CD44 standard and variant-v6 proteins in transitional cell bladder
      tumours and their relation to prognosis during a long-term follow-up.
AB  - The expression of the standard CD44 (CD44s) and its v6 isoform (CD44v6) was
      analysed immunohistochemically in 173 cases of transitional cell bladder cancer.
      The results of immunohistochemical analyses were related to established
      prognostic factors and clinical follow-up data. The expression intensity of CD44s
      in non-basal tumour cells was significantly related to TN classification, S-phase
      fraction (SPF), mitotic index, grade, density of tumour infiltrating lymphocytes.
      The expression intensity of CD44v6 in non-basal tumour cells was inversely
      related to DNA ploidy, SPF, and mitotic index. The expression intensity of CD44v6
      in basal tumour cells was also inversely related to T-category, grade, papillary
      status, DNA ploidy, SPF, and mitotic index. Strong expression of CD44s in non
      basal tumour cells was related to unfavourable outcome in univariate analysis (p
      = 0.008), whereas the strong expression of CD44v6 in both non-basal cells (p =
      0.005) and basal cells (p = 0.0008) was related to high survival probability. In
      multivariate survival analysis, the expression intensity of CD44v6 was
      independently related to favourable outcome in muscle invasive tumours, while in
      superficial tumours, CD44s was an independent prognostic factor. The results
      suggest that the expression of CD44s and CD44v6 is associated with malignant
      features and prognosis in bladder cancer.

PMID- 9924430
TI  - Chromogranin A gene expression in non-small cell lung carcinomas.
AB  - Evidence for the existence of neuroendocrine (NE) differentiation in non-small
      cell lung carcinomas (NSCLCs) is at present based on histochemical,
      ultrastructural, and immunohistochemical data. The aim of this study was to
      investigate the extent of NE differentiation in NSCLCs as revealed by mRNA
      analysis. Different techniques including immunohistochemistry (IHC), northern
      blot analysis (NBA), and reverse transcriptase-polymerase chain reaction (RT-PCR)
      were employed in parallel to reveal the panendocrine marker chromogranin A (CgA).
      The data were related to pathological, immunocytochemical (PGP 9.5,
      synaptophysin, Leu-7 and neuron-specific enolase), and prognostic indicators.
      Forty surgically resected cases of NSCLC (24 squamous cell carcinomas, 12
      ordinary type adenocarcinomas, 3 bronchiolo-alveolar carcinomas, and 1 anaplastic
      large cell carcinoma), in which fresh frozen material was available for mRNA
      analysis, were collected. CgA immunoreactivity was present in five cases (12.5
      per cent), generally confined to a minority of the neoplastic cell population. By
      RT-PCR, CgA mRNA was found in 20 cases (50 per cent), including the five tumours
      positive by IHC. A statistically significant correlation was found between the
      two techniques. By NBA, no CgA mRNA expression was detected. Leu-7
      immunoreactivity was present in 15 per cent of cases, NSE in 52.5 per cent,
      synaptophysin in 10 per cent, and PGP 9.5 in 82.5 per cent. In NSCLC, no
      correlations were found between CgA production, as detected by IHC or RT-PCR
      methods, and the histological type, stage, grade and proliferative activity of
      tumours, or the disease-free interval. It is concluded that CgA gene expression
      can be revealed in NSCLC at both mRNA and protein levels and that RT-PCR is a
      valuable tool for identifying NE differentiated NSCLCs. Our data suggest that NE
      differentiation does not represent an independent prognostic factor in surgically
      resected NSCLCs.

PMID- 9924432
TI  - Detection of oestrogen receptors in non-invasive and invasive transitional cell
      carcinomas of the urinary bladder using both conventional immunohistochemistry
      and the tyramide staining amplification (TSA) technique.
AB  - In a retrospective immunohistochemical study, the expression of oestrogen
      receptors has been investigated in paraffin-embedded transitional cell carcinomas
      of the urinary bladder with antibody 6F11, using both a conventional
      immunohistochemical detection system and the highly sensitive tyramide staining
      amplification (TSA) technique. The study comprised 88 invasive and 97 non
      invasive carcinomas of 101 female (mean age 68.4 years) and 84 male (mean age
      68.2 years) patients. Oestrogen receptors were detected in 34 (18 per cent)
      carcinomas with conventional immunohistochemistry and 46 (25 per cent) with TSA.
      Using TSA, oestrogen receptors were significantly more often detectable in
      invasive (32/88) than in non-invasive carcinomas (14/97) and in G2/G3 (37/122)
      rather than in G1 (9/63) carcinomas. There were no associations between patients'
      age and sex and the expression of oestrogen receptors. The functional
      significance of oestrogen receptor expression in a subset of transitional cell
      carcinomas of the urinary bladder remains to be determined.

PMID- 9924433
TI  - Expression of androgen receptor and growth factors in premalignant lesions of the
      prostate.
AB  - Analysis of growth factors and receptors in putative premalignant lesions of
      prostatic adenocarcinoma should aid our understanding of their growth pathways.
      Sixty prostatic TURP (transurethral resection of the prostate) specimens
      exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic
      intraepithelial neoplasia (PIN) lesions were assayed by immunohistochemistry for
      androgen receptor (AR), epidermal growth factor receptor (EGFR), c-erbB-2,
      transforming growth factor-alpha (TGF-alpha), vascular endothelial growth factor
      (VEGF), fibroblast growth factor-2 (FGF-2), MIB-1, E-cadherin, and high molecular
      weight keratin. Expression of these factors in the lesions was compared with that
      in the co-existing benign prostatic hyperplasia (BPH) or prostatic
      adenocarcinoma. Strong AR nuclear staining was observed in the luminal cells, but
      not the basal cells, of BPH and PIN lesions and in all the carcinomas examined. A
      similar growth factor and receptor profile was demonstrated in the secretory
      epithelium of high-grade PIN and carcinoma with a tendency to higher expression
      of membranous EGFR and c-erbB-2 and cytoplasmic TGF-alpha, and lower levels of
      FGF-2 than in low-grade PIN or BPH glands. Also, increased rates of
      proliferation, as estimated by MIB-1 stained cells, were observed in high-grade
      PIN in comparison with low-grade PIN and BPH and were not confined to the basal
      layer. AAH lesions resembled neither BPH nor carcinoma. Proliferation was
      virtually absent (MIB-1 expression); both AR and E-cadherin expression was
      significantly reduced; and, with the exception of FGF-2, all the other growth
      factors and receptors studied were absent. The results presented would support a
      premalignant role for high-grade PIN, whilst AAH would appear to represent a
      quiescent phenotype unlikely to progress to neoplasia.

PMID- 9924434
TI  - Epithelial-mesenchymal transdifferentiation and extracellular matrix gene
      expression in pleomorphic adenomas of the parotid salivary gland.
AB  - Mesenchymal and epithelial cell differentiation are assumed to be dichotomic
      primary events in embryonic development. In this study, pleomorphic adenomas of
      the parotid gland were analysed as a model which shows morphological features of
      both epithelial and mesenchymal tissue types. Using matrix gene expression
      profiles as a supplementary criterion for the identification of cellular
      phenotypes, areas with unequivocal epithelial and mesenchymal differentiation
      could be demonstrated. Many areas displayed a transitional phenotype with cells
      showing both epithelial and mesenchymal features. The data provide evidence that
      epithelial-mesenchymal transitions represent the basic principle of the tisuse
      heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the
      potential of adult (neoplastic) epithelial cells to transdifferentiate into
      mesenchymal cells in vivo.

PMID- 9924435
TI  - Vascular endothelial growth factor is constitutively expressed in normal human
      salivary glands and is secreted in the saliva of healthy individuals.
AB  - The expression of vascular endothelial growth factor (VEGF), a specific mitogen
      for endothelial cells, was examined in salivary glands and in normal saliva. In
      normal salivary glands, VEGF mRNA and protein were strongly present in acinar
      cells, whereas little or no VEGF was found in ductal cells. In chronically
      inflamed glands, VEGF protein was in addition present in ductal elements and in
      infiltrating mononuclear cells. No difference of VEGF expression was observed
      between benign and malignant salivary gland tumours. By ELISA, whole saliva of 24
      healthy individuals contained up to 2.5 ng/ml (mean 1.4 ng/ml; SD 0.77 ng/ml) of
      VEGF, confirming the constitutive secretion of this cytokine by human salivary
      glands. Western blot analysis of normal saliva under non-reducing conditions
      detected anti-VEGF reactive protein moieties of approximately 46 kD,
      corresponding to VEGF secreted by cells in tissue culture. Additional anti-VEGF
      reactive proteins of approximately 60 and 90 kD were detected in the saliva of
      some individuals. The presence of considerable quantities of VEGF in normal human
      saliva suggests an important role for this cytokine in the maintenance of the
      homeostasis of mucous membranes, with rapid induction of neoangiogenesis by
      salivary VEGF helping to accelerate wound healing within the oral cavity.
      Moreover, salivary VEGF may permeabilize intraglandular capillaries and thus
      participate in the regulation of saliva production itself.

PMID- 9924436
TI  - Hypertrophic scarring is associated with epidermal abnormalities: an
      immunohistochemical study.
AB  - The role of epidermal keratinocytes in the early phases of normal unimpaired
      wound healing has been studied extensively. However, little is known about the
      cell biological processes in the epidermis and the basal membrane zone during the
      later phases of dermal matrix formation and remodelling of the scar tissue. This
      study investigated epidermal growth and differentiation and maturation of the
      basal membrane zone. Biopsies were taken from (clinically) hypertrophic and non
      hypertrophic scars at 3 and 12 months after a breast-reduction operation. Tissues
      were analysed using immunohistochemical techniques. The data showed that
      epidermal abnormalities with respect to differentiation persist up to 3 months,
      as witnessed by the expression of cytokeratin 16. Remarkably, hypertrophic scars
      that remained hypertrophic throughout the period of analysis (up to 12 months)
      showed significantly more cytokeratin 16 expression at 3 months, when compared
      either with normal scars or with hypertrophic scars that became normal after 12
      months. Staining for Ki-67 antigen, a marker for cell proliferation, revealed an
      increase in basal keratinocyte proliferation rate in 3-month-old hypertrophic
      scars compared with non-hypertrophic scars. After 12 months, this difference had
      disappeared completely and the number of cycling basal cells had returned to
      normal values. Three-month-old hypertrophic scars showed more acanthosis than non
      hypertrophic scars of the same age, irrespective of whether they remained
      hypertrophic or became normal scars. After 12 months, this difference was no
      longer present. Staining for various heparan sulphate proteoglycan epitopes
      revealed that restoration of the basal membrane was incomplete at 3 months, but
      was complete at 12 months with respect to this component. No differences in the
      expression of several components of the basal membrane zone (heparan sulphate
      proteoglycan, laminin, tenascin) were noted between hypertrophic and non
      hypertrophic scars. These data show that in the early phase of hypertrophic
      scarring, epidermal abnormalities are found compared with normal wound healing.
      In addition, early (3 months) epidermal abnormalities are associated with the
      clinical outcome at 12 months. These findings raise the possibility that the
      epidermal compartment is involved in the pathogenic process.

PMID- 9924437
TI  - Procollagen-positive fibroblasts predominantly express fibrogenic growth factors
      and their receptors in human encapsulation process against foreign body.
AB  - This paper addresses the in situ expression of transforming growth factor-beta
      (TGF-beta), platelet-derived growth factor (PDGF), and their receptors in the
      encapsulation process against a foreign body, using 20 cases of the titanium
      miniplate as a model of the foreign body, used clinically to fix a fractured
      mandible. Fibrous tissue formed during the encapsulation process was composed of
      scar-like and fibrogenic layers, with the former directly facing the foreign
      body. By immunohistochemistry using pre-fixed frozen sections, only the
      fibrogenic layer was characterized by expression of type I procollagen (PC-I).
      Spindle-shaped mesenchymal cells in the fibrogenic layer expressed TGF-beta
      isoforms and receptors, PDGF isoforms, and PDGF beta-receptor. In contrast, the
      scar-like layer had few such cells. In both layers, spindle-shaped cells did not
      express Ki-67 in their nuclei. Double immunofluorescence microscopy for cell
      identification revealed that most PC-I-positive fibroblasts expressed both
      isoforms and receptors of TGF-beta and PDGF in the fibrogenic layer, while in
      contrast, they were expressed by only a small number of CD68-positive
      macrophages. These results suggest that in the maintenance stage of the human
      encapsulation process against a foreign body, both TGF-beta and PDGF function
      cooperatively via their receptors in the fibrogenic layer, with such stimuli
      markedly diminished in the scar-like layer.

PMID- 9924438
TI  - Tumours derived from HTLV-I tax transgenic mice are characterized by enhanced
      levels of apoptosis and oncogene expression.
AB  - In order to investigate the role that the human T-lymphotropic virus type I (HTLV
      I) tax oncogene plays in apoptosis and transformation in vivo, four lines of HTLV
      I tax transgenic mice were generated under the regulatory control of the CD3
      epsilon promoter-enhancer sequence. These mice develop a variety of phenotypes
      including mesenchymal tumours, which develop at wound sites, and salivary and
      mammary adenomas. In situ DNA fragment labelling and immunocytochemical analysis
      of these tumours reveals that they display enhanced levels of apoptosis, which is
      associated with elevated levels of Myc, Fos, Jun, and p53 protein expression.
      Furthermore, double immunofluorescent staining shows that Tax expression and
      apoptosis co-localize, indicating that Tax expression is closely associated with
      apoptosis in vivo.

PMID- 9924439
TI  - An animal model for copper-associated cirrhosis in infancy.
AB  - In Indian childhood cirrhosis (ICC) and related disorders of infancy, hepatic
      copper overload is associated with cirrhosis. Since copper administration alone
      has not been shown to induce cirrhosis in animals, synergy between copper and a
      second hepatotoxin has been suggested. This study investigates the ability of
      long-term exposure to copper and a pyrrolizidine alkaloid, retrorsine, to produce
      a model of copper-associated cirrhosis in rats. Groups of rat pups suckled on
      mothers fed 25 mg/kg diet retrorsine were weaned onto a diet containing 0.5 g/kg
      diet copper and retrorsine in varying dosage for 13 weeks. Histological
      similarities between the human disease and rats given copper with retrorsine 5
      mg/kg diet included parenchymal destruction, fibrosis, nodular regeneration, and
      copper accumulation. There were significant histological differences from the
      human disorder, possibly attributable to inter-species variability or the
      critical timing or duration of exposure to hepatotoxins in the neonatal period.
      The hypothesis that ICC results from copper and a second hepatotoxin has not been
      disproved.

PMID- 9924440
TI  - Proposal for the assessment of quantitative dermal exposure limits in
      occupational environments: Part 1. Development of a concept to derive a
      quantitative dermal occupational exposure limit.
AB  - Dermal uptake of chemicals at the workplace may contribute considerably to the
      total internal exposure and so needs to be regulated. At present only qualitative
      warning signs--the "skin notations"--are available as instruments. An attempt was
      made to develop a quantitative dermal occupational exposure limit (DOEL)
      complementary to respiratory occupational exposure limits (OELs). The DOEL refers
      to the total dose deposited on the skin during a working shift. Based on
      available data and experience a theoretical procedure for the assessment of a
      DOEL was developed. A DOEL was derived for cyclophosphamide and 4,4-methylene
      dianiline (MDA) according to this procedure. The DOEL for MDA was tested for
      applicability in an actual occupational exposure scenario. An integrated approach
      is recommended for situations in which both dermal and respiratory exposures
      contribute considerably to the internal exposure of the worker. The starting
      point should be an internal health based occupational exposure limit--that is,
      the maximum dose to be absorbed without leading to adverse systemic effects. The
      proposed assessment of an external DOEL is then either based on absorption rate
      or absorption percentage. The estimation of skin penetration seems to be of
      crucial importance in this concept. If for a specific substance a maximal
      absorption rate can be estimated a maximal skin surface area to be exposed can be
      assessed which may then serve the purpose of a DOEL. As long as the actual skin
      surface exposed is smaller than this maximal skin surface area the internal OEL
      will not be exceeded, and therefore, no systemic health problems would be
      expected, independent of the dermal dose/unit area. If not, the DOEL may be
      interpreted as the product of dermal dose/unit area (mg/cm2) and exposed skin
      surface area (cm2). The proposed concept for a DOEL is relevant and can be made
      applicable for health surveillance in the occupational situation where dermal
      exposure contributes notably to the systemic exposure. Further research should
      show whether this concept is more generally applicable.

PMID- 9924441
TI  - Proposal for the assessment to quantitative dermal exposure limits in
      occupational environments: Part 2. Feasibility study for application in an
      exposure scenario for MDA by two different dermal exposure sampling methods.
AB  - OBJECTIVE: To evaluate two different techniques for assessing dermal exposure to
      4,4'-methylene dianiline (MDA) in a field study. The results were used to test
      the applicability of a recently proposed quantitative dermal occupational
      exposure limit (DOEL) for MDA in a workplace scenario. METHODS: For two
      consecutive weeks six workers were monitored for exposure to MDA in a factory
      that made glass fibre reinforced resin pipes. Dermal exposure of the hands and
      forearms was assessed during week 1 by a surrogate skin technique (cotton
      monitoring gloves) and during week 2 by a removal technique (hand wash). As well
      as the dermal exposure sampling, biological monitoring, measurement of MDA
      excretion in urine over 24 hours, occurred during week 2. Surface contamination
      of the workplace and equipment was monitored qualitatively by colorimetric wipe
      samples. RESULTS AND CONCLUSIONS: Geometric means of daily exposure ranged from
      81-1762 micrograms MDA for glove monitoring and from 84-1783 micrograms MDA for
      hand washes. No significant differences, except for one worker, were found
      between exposure of the hands in weeks 1 and 2. Significant differences between
      the mean daily exposure of the hands (for both weeks and sampling methods) were
      found for all workers. The results of the colorimetric wipe samples indicated a
      general contamination of the workplace and equipment. Excretion of MDA in 24 hour
      urine samples ranged from 8 to 249 micrograms MDA, whereas cumulative MDA
      excretion over a week ranged from 82 to 717 micrograms MDA. Cumulative hand wash
      and MDA excretion results over a week showed a high correlation (R2 = 0.94). The
      highest actual daily dermal exposure found seemed to be about 4 mg (hand wash
      worker A on day 4), about 25% of the external DOEL. Testing of compliance by
      means of a biological limit value (BLV) led to similar results for the same
      worker. It is concluded that both dermal exposure monitoring methods were
      applicable and showed a compatible performance in the present exposure scenario,
      where the exposure relevant to dermal absorption is considered mainly restricted
      to hands. The concept for a DOEL seemed to be relevant and applicable for
      compliance testing and health surveillance in the situation under investigation.

PMID- 9924442
TI  - Does living near a constellation of petrochemical, steel, and other industries
      impair health?
AB  - OBJECTIVES: To investigate concern that local industrial air pollution in
      Teesside, England, was causing poor health, several areas there were compared
      with parts of the City of Sunderland. METHODS: Populations in similar social and
      economic circumstances but varying in their proximity to major industries were
      compared. Study populations lived in 27 housing estates in Teesside and
      Sunderland, north east England, with some data from subsets of estates. The
      estates were aggregated into zones (designated as A, B, and C in Teesside where A
      is closest to and C furthest from industry, and S in Sunderland). Zone S provided
      a reference area. The hypothesis was that a health gradient both within Teesside
      (A > B > C) and between Teesside and Sunderland (ABC > S) would indicate a
      possible health effect of local industrial air pollution. Data presented were:
      mortality (1981-91) from 27 housing estates; population self completion
      questionnaire survey data (1993, 9115 subjects) from 15 housing estates; and
      general practitioner (GP) consultation data (1989-94) from 2201 subjects in 12
      Teesside estates. RESULTS: The populations in the four zones were comparable for
      indicators including smoking habits, residential histories, and unemployment. All
      cause and cause specific mortalities were high compared with England and Wales.
      Mortality in all Teesside zones (ABC) combined was mostly higher than in zone S.
      In people aged 0-64, lung cancer and respiratory disease showed gradients with
      highest mortality in areas closest to industry (A > B > C and ABC > S). The
      association was clearest for lung cancer in women (0-64 years old, trend across
      zones ABC, p = 0.07, directly standardised rate ratio relative to zone S was 169
      (95% confidence interval (95% CI) 116-122)). There were no important, consistent
      gradients in the hypothesised direction between zones in consultation rates in
      general practice, and self reported respiratory and nonrespiratory health
      including asthma. CONCLUSIONS: There was no clear evidence that living close to
      industry was associated with morbidity, including asthma, or for most measures of
      mortality. For lung cancer in women the gradients indicated a health effect of
      local industrial air pollution. In the age group 0-64 observed gradients in lung
      cancer in men and mortality from respiratory disease in men and women were
      consistent with the study hypothesis, although not significant. The reasons for
      the different patterns at different ages, and between men and women, remain a
      puzzle.

PMID- 9924443
TI  - Evaluation of chronic respiratory effects in the potato processing industry:
      indications of a healthy worker effect?
AB  - OBJECTIVE: To investigate the occurrence of chronic respiratory effects of
      exposure to organic dust in the potato processing industry. METHODS: Self
      reported chronic respiratory symptoms and spirometric lung function were assessed
      in a cross sectional study among 135 potato processing workers. A comprehensive
      study of current exposure to dust, endotoxin, and potato antigens had been
      performed previously. Workers were grouped into low and high exposure categories
      for each of the three exposure indices. Relations between exposure concentrations
      and respiratory health variables were investigated either by calculating
      prevalence rate ratios or by performing linear regression analyses. Atopy was
      assessed by measuring total immunoglobulin E (IgE) and specific IgE to five
      common aeroallergens in serum samples of workers. RESULTS: Evident relations
      between current exposure indices and respiratory health in the entire group were
      not found. Workers employed < or = 5 years showed a two-fold higher prevalence of
      respiratory symptoms, lower lung function, and higher endotoxin exposure than
      workers employed for > 5 years. Also, atopy was more prevalent in workers
      employed < or = 5 years. After stratification for duration of employment,
      negative effects of endotoxin on lung function among workers employed < or = 5
      years were suggested. CONCLUSIONS: This study does not show chronic respiratory
      effects of exposure to organic dust in the potato processing industry, despite
      the fact that the levels of exposure to endotoxin found in this industry have
      been reported to be associated with decreases in lung function in other
      occupational settings. A likely explanation for not detecting apparent effects
      might be that many symptomatic workers drop out of this industry a few years
      after starting the job, suggesting a healthy worker effect.

PMID- 9924444
TI  - Smoking and musculoskeletal disorders in the metal industry: a prospective study.
AB  - OBJECTIVES: To obtain longitudinal information of the relation between smoking
      and musculoskeletal disorders in an industrial setting. METHODS: The associations
      of lifetime tobacco exposure (pack-years), current smoking status, and stopping
      smoking with back and limb disorders were studied in a cohort of white collar and
      blue collar employees in a metal industry. Measurements were made three times at
      5 year intervals. Two thirds of an initial sample of 902 took part in both re
      examinations. Musculoskeletal morbidity was measured as the abundance of symptoms
      during the past year and as clinical findings assessed by a physiotherapist
      (upper decile score/score difference = index category). Logistic regression and a
      generalised estimating equation were used, allowing for sociodemographic
      variables, physical workload, body mass index, exercise activity, and mental
      distress. RESULTS: By comparison with never smokers, exposure of 10-< 20 pack
      years, the odds ratio (OR) (95% confidence interval (95% CI) of the 10 year
      change in neck-shoulder symptoms was 3.1 (1.4 to 6.8), in low back symptoms 2.4
      (1.1 to 5.1), in upper limb symptoms 1.9 (NS), and in lower limb symptoms 3.4
      (1.5 to 7.8). The highest exposure category of > or = 20 pack-years was
      associated with the change in upper limb findings 2.9 (1.4 to 6.2) and lower limb
      findings 2.9 (1.2 to 7.2). Those who continued to smoke through the follow up
      period had a higher increase in clinical findings 2.5 (1.1 to 5.9) than never
      smokers. There was a dose-response in the association of smoking intensity with
      future musculoskeletal symptoms. Also, those who stopped smoking during the
      follow up had a higher increase in symptoms 4.4 (2.0 to 9.9) and findings 3.5
      (1.4 to 8.8) than never smokers. CONCLUSION: Smoking seems to predict the
      development in the occurrence of musculoskeletal symptoms and signs. Stopping
      smoking is associated with high morbidity.

PMID- 9924446
TI  - Asbestos lung burden and asbestosis after occupational and environmental exposure
      in an asbestos cement manufacturing area: a necropsy study.
AB  - OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale
      Monferrato until 1986: in previous studies a substantial increase in the
      incidence of pleural mesothelioma was found among residents without occupational
      exposure to asbestos. To estimate exposure to asbestos in the population, this
      study evaluated the presence of histological asbestosis and the lung burden of
      asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the
      consecutive series of necropsies performed at the Hospital of Casale Monferrato
      between 1985 and 1988. A sample of lung parenchima was collected and stored for
      48 out of 55 necropsies. The AF concentration was measured with a TEM electron
      microscope with x ray mineralogical analysis. The ABs were counted and fibrosis
      evaluated by optical microscopy. The nearest relative of each subject was
      interviewed on occupational and residential history. Mineralogical and
      histological analyses and interviews were conducted in 1993-4. RESULTS:
      Statistical analyses included 41 subjects with AF, AB count, and interview.
      Subjects without occupational exposure who ever lived in Casale Monferrato had an
      average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with
      asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two
      women with no occupational asbestos exposure. One of them had been teaching at a
      school close to the factory for 12 years. Ten subjects had experienced
      occupational asbestos exposure, seven in asbestos cement production: mean
      concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had
      asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding
      of environmental asbestosis confirm that high asbestos concentration was common
      in the proximity of the factory. Subjects not occupationally exposed and ever
      living in Casale Monferrato tended to have higher AB concentration than subjects
      never living in the town (difference not significant). The concentrations of ABs
      and AFs were higher than those found in other studies on nonoccupationally
      exposed subjects.

PMID- 9924445
TI  - Respiratory health of cigar factory workers.
AB  - OBJECTIVES: To determine whether occupational exposure to raw tobacco causes
      respiratory or allergic diseases, an excess of respiratory symptoms, a decrease
      in lung function, or parenchymal changes in chest radiography among Finnish cigar
      workers. METHODS: This cross sectional study included all Finnish cigar workers
      (n = 106) exposed to raw tobacco and also a group of unexposed matched referents.
      Data were collected with a self administered questionnaire, flow volume
      spirometry, measurements of diffusing capacity of the lung for carbon monoxide,
      chest radiography and skin prick tests. A questionnaire was also sent to former
      workers of the factory. RESULTS: There were no significant differences between
      the groups in the prevalence of respiratory symptoms and chest radiography
      findings. Nine of 102 tobacco workers had pulmonary fibrosis of at least 1/0
      (according to the International Labour Organisation (ILO) 1980 classification)
      and the corresponding figure was five for the referents. The tobacco workers
      tended to have a low forced vital capacity (FVC), and they had impaired forced
      expiratory volume in 1 second and lower means of the maximal expiratory flow at
      25% of the FVC significantly more often than the referents. Diffusing capacity
      tended to be lower among the referents. The referents more often had atopy and
      earlier atopic diseases than the exposed workers. These results indicate the
      possibility of selection among the exposed workers. CONCLUSIONS: No excess of
      prevalence of respiratory symptoms in the tobacco workers was found. According to
      the questionnaire episodes of allergic alveolitis may have occurred in the cigar
      factory workers. However, in the absence of impairments in lung function and
      radiological changes it was not possible to distinguish humidifier fever and
      allergic alveolitis. In exposure conditions that include humidification of the
      air humidifier, fever and allergic alveolitis constitute a risk for tobacco
      workers. No effects were shown of exposure to tobacco dust on lung function.

PMID- 9924447
TI  - An epidemiological study of acute carbon monoxide poisoning in the West Midlands.
AB  - OBJECTIVES: To describe the epidemiology of carbon monoxide (CO) poisoning in a
      defined population, identifying those at greatest risk from acute poisoning
      resulting in admission to hospital or death. METHODS: A retrospective study with
      routinely collected information, set in the former West Midlands Regional Health
      Authority; population of 5.2 million. The data comprised 939 deaths and 701
      hospital admissions due to CO poisoning between January 1988 to December 1994.
      The main outcome measures were age and sex standardised incidence rates (SIRs)
      for non-intentional, suicidal, and undetermined poisonings for health authorities
      and the linear relation with socioeconomic deprivation. RESULTS: Overall rate of
      non-intentional poisonings over the 7 year period was 7.6/100,000, an annual rate
      of 1.1/100,000. The 7 year rates were highest in people > or = 85; men
      24.0/100,000 and women 19.7/100,000. For suicides the 7 year rate was
      19.6/100,000, an annual rate of 2.8/100,000. The 7 year rates were highest for
      men of 35-39, 64.1/100,000, and for women aged 45-49, 15.3/100,000. None of the
      causes of poisoning were related to deprivation. Non-intentional poisonings
      showed a strong seasonal variation with the highest rates being recorded in the
      months October to March. Increased rates of poisoning were found in the rural
      districts of the West Midlands. There seems to have been a decline in suicides
      coinciding with the introduction of three way catalytic converters on cars.
      CONCLUSIONS: Elderly people and the very young are at the greatest risk from non
      intentional CO poisoning and rates are highest in the winter months. Although
      deaths from non-intentional CO poisoning are declining nationally, in the West
      Midlands they have remained stable and hospital admissions are increasing. It is
      not solely an urban phenomenon with rates for non-intentional CO poisoning and
      suicides higher in the rural districts. Health authorities need to consider all
      populations in any prevention programme. Further work is needed to establish the
      extent of the burden of chronic CO poisoning and the impact of catalytic
      converters on suicides.

PMID- 9924448
TI  - Stress in farmers: a survey of farmers in England and Wales.
AB  - OBJECTIVES: To investigate potential sources of stress for farmers in England and
      Wales METHOD: A postal questionnaire was sent to a randomly selected group of 800
      members of the National Farmers' Union and 200 members of the Farmers' Union of
      Wales. RESULTS: 500 questionnaires (51%) were returned completed between October
      1995 and March 1996. Farmers had problems with record keeping and paperwork
      (62%), difficulty understanding forms (56%), and problems arising from the
      effects of new legislation and regulations (49%). Nearly a quarter (23%) reported
      financial problems and most worried about money (79%). Very few were socially
      isolated, with over 90% having at least one confidant. 70% worked > 10 hours a
      day, and 31% had health problems which interfered with their work, including more
      than a quarter of those < 50. 16% of the sheep farmers reported symptoms which
      they attributed to organophosphate poisoning. The farmers most vulnerable to
      financial and other problems were those with small farms and mixed farming
      operations. Farmers in Wales also seemed more vulnerable than those in England,
      but a lower response rate from members of the Farmers' Union of Wales means this
      difference should be interpreted cautiously. CONCLUSION: The survey confirms
      findings from several regional studies that many farmers are experiencing
      considerable stress from various causes. Local and national initiatives to assist
      farmers, including outreach programmes, should be encouraged. Policy makers
      should be aware of the potential impact of legislation, particularly on the more
      vulnerable groups.

PMID- 9924449
TI  - Psychosocial factors at work and sickness absence in the Gazel cohort: a
      prospective study.
AB  - OBJECTIVE: To test whether psychosocial factors at work are predictors of rates
      of sickness absence. METHODS: The study population consisted of middle aged men
      and women employed by the French national electricity and gas company (EDF-GDF)
      in various occupations and followed up since 1989 by annual self administered
      questionnaires and independent data obtained from the medical and personnel
      departments of EDF-GDF. The 1995 questionnaire provided information about three
      psychosocial work factors: psychological demands, decision latitude, and social
      support at work. Sick-ness absence data were provided by the company's social
      security department. The occurrence of spells and days of absence in the 12
      months after completion of the 1995 questionnaire was studied. Potential
      confounding variables were age, smoking, alcohol, and marital status, assessed in
      the 1995 questionnaire, and educational level and occupation, assessed from data
      provided by the personnel department. This study was restricted to the 12,555
      subjects of the initial cohort who were still working and answered the self
      administered questionnaire in 1995. RESULTS: Low levels of decision latitude were
      associated with more frequent and longer sickness absences among men and women.
      Low levels of social support at work increased the numbers of spells and days of
      absence among men only. These associations weakened after adjustment for
      potential confounding factors, but remained significant. CONCLUSION: The study
      indicates that psychosocial factors at work, especially decision latitude, are
      predictive of sickness absence.

PMID- 9924450
TI  - Immunological markers among workers exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin.
AB  - OBJECTIVES: To examine the association of immune cell number and function with
      occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD). METHODS: A cross sectional medical survey. The exposed
      participants were employed at two chemical plants between 1951 and 1972 in the
      manufacture of 2,4,5-trichlorophenate and its derivatives. The reference group
      consisted of people with no occupational exposure to phenoxy herbicides who lived
      within the communities of the workers. Data from a total of 259 workers and 243
      unexposed referents were included in the analysis of immune function. Laboratory
      tests for immune status included enumeration of circulating leukocyte and
      lymphocyte populations, proliferative responses of circulating lymphocytes to
      mitogens and antigens, and serum concentrations of the major immunoglobulins and
      complement factor C3. RESULTS: The workers had substantial exposure to substances
      contaminated with TCDD, as indicated by a lipid adjusted mean serum TCDD
      concentration of 229 ppt compared with a mean of 6 ppt in the unexposed
      referents. Workers were divided into categories based on their serum TCDD
      concentration. For all categories except the lowest, with values of serum TCDD
      comparable with the unexposed referents, there were increased odds of having
      lower counts of CD26 cells (activated T cells) (odds ratio (OR) 1.0, 95%
      confidence interval (95% CI) 0.5 to 1.8 for TCDD < 20 ppt; OR 1.6, 95% CI 0.8 to
      3.2 for TCDD 20-51 ppt; OR 2.7, 95% CI 1.4 to 5.1 for TCDD 52-125 ppt; OR 2.6,
      95% CI 1.4 to 4.9 for TCDD 125-297 ppt; OR 2.4, 95% CI 1.3 to 4.6 for TCDD 298
      3389 ppt). A less consistent finding was decreased spontaneous proliferation of
      cultured lymphocytes. However, increases were found in proliferation of
      lymphocytes in response to concanavalin and pokeweed in workers in the high TCDD
      category. Age, cigarette smoking, and alcohol were significant predictors of
      several immunological outcomes. CONCLUSIONS: Associations between serum TCDD
      concentration and both a decrease in circulating CD26 cells and decreased
      spontaneous background proliferation were the major findings of this study. These
      results are unlikely to be of clinical importance but may reflect limited
      evidence for an association between immunological changes in workers and high
      serum concentrations of TCDD, or chance findings resulting from the evaluation of
      multiple immunological variables.

PMID- 9924451
TI  - Occurrence of self reported hand eczema in Swedish bakers.
AB  - OBJECTIVES: To estimate the risk of bakers developing hand eczema. The importance
      of atopy was studied as well as change of job due to hand eczema. METHODS: A
      retrospective cohort study was performed among bakers trained in Swedish trade
      schools in 1961-89 (n = 2923). School referents followed other programmes (n =
      1258); population controls were randomly selected from the general population (n
      = 1258). A questionnaire on self reported hand eczema, year of onset of hand
      eczema, change of work due to hand eczema, childhood eczema, family atopy, and
      work history was posted to all participants. RESULTS: The incidence of hand
      eczema among male controls was 4.4-5.4 cases/1,000 person-years compared with
      16.7 for bakery work. The corresponding figures for women were 11.3-14.1 compared
      with 34.4. The relative risk for male bakers was 3.5 (95% confidence interval
      (95% CI) 2.8 to 4.5) and for female bakers 2.8 (2.2 to 3.6). Skin atopy increased
      the incidence about threefold and a synergistic effect of atopy and exposure was
      indicated. Also, bakers had changed job significantly more often than controls.
      CONCLUSIONS: Swedish bakers, mainly working during the 1970s and 1980s, have
      about a threefold increased risk of hand eczema. There seems to be a synergistic
      effect of atopy and occupational exposure.

PMID- 9924452
TI  - Mortality and cancer incidence in Swedish battery workers exposed to cadmium and
      nickel.
AB  - OBJECTIVE: To follow up cancer incidence and mortality in a group of Swedish
      battery workers exposed to nickel hydroxide and cadmium oxide. METHODS: 869
      workers, employed at least one year between the years 1940 and 1980 were followed
      up until 1992. Vital status and causes of death were obtained from the Swedish
      cause of death registry. Cancer morbidity was retrieved from the Swedish cancer
      registry. Regional reference rates were used to compute the expected numbers of
      deaths and cancers. RESULTS: Up to 31 December, 1992, a total of 315 deaths (292
      in men and 23 in women) had occurred in the cohort. For men, the overall
      standardised mortality ratio (SMR) was 106 (95% confidence interval (95% CI) 93.7
      to 118) and for women 83.8 (95% CI 53.1 to 126). The SMRs for total cancer
      mortality were 125 (95% CI 98.2 to 157) for men and 69.5 (95% CI 25.5 to 151) for
      women. The SMR for lung cancer in men was 176 (95% CI 101 to 287). No lung
      cancers were found among female workers. Up to 31 December, 1991, a total of 118
      cancers had occurred in the cohort. A significantly increased standardised
      incidence ratio (SIR) was found for cancer of the nose and nasal sinuses in men,
      three cases v 0.36 expected, yielding an SIR of 832 (95% CI 172 to 2430).
      Applying a 10 year latency period in cohort members exposed to > or = 1000
      micrograms cadmium/m3, the SIR was 1107 (95% CI 134 to 4000). Similarly, for
      cohort members exposed to 2000 micrograms nickel/m3, the SIR was 1080 (95% CI 131
      to 3900). CONCLUSION: There was an increased overall risk for lung cancer, but no
      exposure-response relation between cumulative exposure to cadmium or nickel and
      risk of lung cancer. There was a highly significant increased risk of cancer of
      the nose and nasal sinuses, which may be caused by exposure to nickel or cadmium
      or a combination of both exposures.

PMID- 9924453
TI  - Estimation of the past and future burden of mortality from mesothelioma in
      France.
AB  - OBJECTIVES: Firstly to evaluate future mortality from mesothelioma in France with
      an age-period-cohort approach and evaluate different hypotheses on risk of
      mesothelioma for the most recent birth cohort. Secondly to compare the results
      with a British and an American study. Thirdly to study if any trends were
      detectable on data for women which would be consistent with the consequences of
      increasing environmental exposure to asbestos. METHODS: Estimates of mortality
      from mesothelioma among men and women in France from 1950 to 1995 were based on
      the analysis of the pleural cancer mortality data coded 163 in the ninth revision
      of the international classification of diseases (ICD-9). Correction factors were
      used to derive the mortality from mesothelioma from these data, based on two
      regional registries. The analysis of the past mortality data has been performed
      by an age-cohort model (with a maximum likelihood technique). Predictions of
      deaths from mesothelioma over the next 50 years were based on four different
      assumptions on the risk of death from mesothelioma in future birth cohorts.
      RESULTS: The predicted lifetime probability of dying from mesothelioma increases
      until the last birth cohort 1964-8 among men whereas it decreases strongly from
      the 1954-8 birth cohort among women. The projected numbers of deaths from
      mesothelioma in France until 2020 are similar, whichever hypothesis is
      considered: around 20,000 deaths from mesothelioma might occur among men and 2900
      among women from 1996 to 2020. CONCLUSIONS: French data show an increasing
      lifetime probability of death from mesothelioma in the more recent male cohorts.
      Although the mortality burden can be predicted until 2020, and is intermediate
      between the United Kingdom and United States estimates, there is still high
      uncertainty on the figures after 2020. No increase is found in women, and this
      does not support the hypothesis that current environmental exposure to asbestos
      could be associated with a detectable risk of death. Specific surveillance should
      be set up to monitor future trends or their absence.

PMID- 9924454
TI  - Lung cancer and mesothelioma in the pleura and peritoneum among Swedish
      insulation workers.
AB  - OBJECTIVES: To estimate the risk of cancer and death in Swedish insulation
      workers some years after their exposure to asbestos had stopped. One hypothesis
      was that the risk of lung cancer would tend to decrease some years after the
      exposure had ended. METHODS: In a cohort study the cancer morbidity and cause of
      death was investigated in 248 insulation workers and compared with the
      corresponding morbidity and mortality in the general population. Due to stringent
      regulations, exposure to asbestos of all types had almost ended in Sweden in the
      mid-1970s. Through a questionnaire, surviving insulation workers were asked about
      their exposure to asbestos and their smoking habits. RESULTS: Between 1970 and
      1994 there were 86 deaths compared with the 46.0 expected (standardised incidence
      ratio (SIR) 1.9; 95% confidence interval (95% CI) 1.5 to 2.3), the increase was
      mainly due to an increased cancer mortality. The morbidity was increased for lung
      cancer (11 cases v 2.5 expected (SIR 4.4; 95% CI 2.2 to 7.9)), peritoneal
      mesothelioma (seven cases; no expected incidence could be calculated as the
      occurrence is too rare in the general population), cancer in pancreas (five cases
      v 0.7 expected (SIR 7.1; 95% CI 2.3 to 16.7)). No cases of pleural mesothelioma
      were found. The risk of lung cancer did not tend to approach that of the general
      population after the exposure to asbestos decreased. CONCLUSIONS: In the 1980s
      and the early 1990s, Swedish insulation workers still have a highly increased
      risk of diseases related to asbestos. The attributable risk for death and cancer
      was about 50%. The study also confirms the previous finding that mesothelioma in
      insulation workers seems to be situated in the peritoneum more often than in the
      pleura.

PMID- 9924455
TI  - Road traffic and adverse respiratory effects in children. SIDRIA Collaborative
      Group.
AB  - OBJECTIVES: To investigate the relation between traffic indicators in the area of
      residence and the occurrence of chronic respiratory disorders in children.
      METHODS: A population based survey was conducted in 10 areas of northern and
      central Italy (autumn 1994 to winter 1995) in two age groups (6-7 and 13-14
      years). Information on several respiratory disorders and on traffic near
      residences was collected with a questionnaire given to children and to their
      parents. The sample analysed included 39,275 subjects (response rate 94.4%).
      Outcomes were: (a) early (first 2 years of life) respiratory diseases, and (b)
      current respiratory disorders (asthma, wheeze, cough, or phlegm in the past
      year). Odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for
      several potential confounders, were estimated from logistic regression models.
      Main results were stratified by level of urbanisation (metropolitan areas, other
      centres). RESULTS: In the metropolitan areas, high frequency of lorry traffic in
      the street of residence was associated with significantly increased risks for
      many adverse respiratory outcomes. Among early respiratory diseases, the
      strongest associations were found for recurrent bronchitis (OR 1.69, 95% CI 1.24
      to 2.30), bronchiolitis (1.74, 1.09 to 2.77) and pneumonia (1.84, 1.27 to 2.65),
      although no association was detected for episodes of wheezing bronchitis. All the
      current respiratory disorders were positively and consistently associated with
      frequency of lorry traffic, particularly the most severe bronchitic and wheezing
      symptoms: persistent phelgm for > 2 months (1.68; 1.14 to 2.48), and severe
      wheeze limiting speech (1.86; 1.26 to 2.73). No or weaker associations with heavy
      vehicular traffic were detected in urban and rural areas and no increased risks
      were found in the whole sample with the reported traffic density in the zone of
      residence. After extensive evaluations, the potential of reporting bias seems
      unlikely. CONCLUSION: Exposure to exhausts from heavy vehicular traffic may have
      several adverse effects on respiratory health of children living in metropolitan
      areas, increasing the occurrence of lower respiratory tract infections early in
      life and of wheezing and bronchitic symptoms at school age.

PMID- 9924456
TI  - Crystalline silica and risk of lung cancer in the potteries.
AB  - OBJECTIVE: To evaluate crystalline silica as a human carcinogen. METHODS: A
      cohort of 5115 men, born 1916-45 and employed in the pottery, refractory, and
      sandstone industries of Stoke-on-Trent was identified from occupations subject to
      health surveillance by the local Silicosis Medical Board (now the Department of
      Social Security). Detailed occupational and smoking histories, and records of
      small parenchymal opacities on periodic radiographs were extracted from medical
      records. An exposure matrix was derived from some 1400 personal or static dust
      samples and tested against the presence of small parenchymal opacities in a
      subcohort of 1080 men employed for at least 10 years, who had started working in
      the industry before 1960. RESULTS: Standardised mortality ratios (SMRs)
      calculated against mortalities for Stoke-on-Trent, with 95% confidence intervals
      (95% CIs), were raised for all causes (1.15 (1.05 to 1.26)), lung cancer (1.28
      (0.99 to 1.62)) and non-malignant respiratory disease (2.04 (1.55 to 2.65)).
      Average concentration and duration of exposure to silica were, taken together,
      significantly related to the presence of small opacities (> or = 1/0). In a
      nested case-referent analysis of 52 cases of lung cancer and 197 matched
      referents, conditional logistic regression gave a significantly increased odds
      ratio (OR) for average silica concentration (micrograms/m3.100), after adjustment
      for smoking, of 1.66 (1.14 to 2.41) but not for duration of exposure nor, in
      consequence, for cumulative exposure. CONCLUSION: The association between risk of
      lung cancer and quantitative estimates of silica exposure supports the SMR
      analysis and implies that crystalline silica may well be a human carcinogen.

PMID- 9924457
TI  - Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers.
AB  - OBJECTIVES: To study the role of individual and occupational risk factors for
      asthma in furniture workers. METHODS: 296 workers were examined (258 men, 38
      women) with a questionnaire of respiratory symptoms and diseases, baseline
      spirometry, bronchial provocative test with methacholine, and skin prick tests.
      Non-specific bronchial hyperreactivity was defined as when a provocative dose
      with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8
      mg and atopy in the presence of at least one positive response to skin prick
      tests. Workers were subdivided into spray painters (exposed to low concentrations
      of diisocyanates and solvents), woodworkers (exposed to wood dusts), and
      assemblers (control group). RESULTS: The prevalences of attacks of shortness of
      breath with wheezing and dyspnoea were higher in spray painters (13.5% and 11.5%
      respectively) than in woodworkers (7.7% and 6.3%) or in assemblers (1.6% and
      1.6%); prevalences of chronic cough, asthma, and rhinitis were also slightly but
      not significantly higher in spray painters and in woodworkers than in assemblers.
      The difference in the prevalence of respiratory symptoms among the job titles was
      due to the atopic subjects, who showed a higher prevalence of chronic cough,
      wheeze, shortness of breath with wheeze, dyspnoea, and asthma in spray painters
      than in the other groups. The prevalence of non-specific bronchial
      hyperreactivity in subjects who performed bronchial provocative tests was 17.7%,
      with no significant difference among groups. Asthma symptoms were significantly
      associated with non-specific bronchial hyperreactivity. Asthma-like symptoms plus
      non-specific bronchial hyperreactivity was found in 4% of assemblers, 10% of
      woodworkers, and 13.3% of spray painters (chi 2 = 2.6, NS). Multiple logistic
      analysis taking into account individual (smoke, atopy, age) and occupational (job
      titles) risk factors confirmed that spray painters had higher prevalence of
      chronic cough than assemblers, and a trend in increasing the prevalence of
      shortness of breath with wheeze, dyspnoea, and asthma. CONCLUSIONS: Painters in
      the furniture industry, particularly atopic subjects, are at higher risk of
      asthma-like symptoms than other job titles. In these workers asthma-like symptoms
      are more sensitive than non-specific bronchial hyperreactivity in detecting a
      negative effect of the occupational exposure.

PMID- 9924459
TI  - Monetary incentives: a useful strategy for enhancing enrollment and promoting
      participation in HIV/STD risk reduction interventions.

PMID- 9924458
TI  - Does the US Navy attract young women who smoke?
AB  - OBJECTIVE: To assess whether the United States Navy is disproportionately
      attracting and recruiting female smokers from the civilian sector. METHODS:
      Standardised comparisons of cigarette use among Navy women recruits and civilian
      women were conducted with data from a 1996-97 Department of Defense study and the
      1994 National Health Interview Survey. RESULTS: Young Navy women recruits (18-22
      years) had significantly higher rates of current and heavy smoking than their
      civilian counterparts after adjusting for differences in sociodemographic
      characteristics. Smoking rates among older recruits and civilian women (23-30
      years) were not significantly different. CONCLUSIONS: It seems that the Navy
      attracts young civilian women who already smoke, many of whom smoke heavily.

PMID- 9924460
TI  - Tuberculosis recommendations.

PMID- 9924461
TI  - HIV drug resistance: genotypic assays and their possible applications.

PMID- 9924462
TI  - Prepackaged therapy for urethritis: the "MSTOP" experience in Cameroon.
AB  - RATIONALE: The social marketing of STD treatment may be a strategy to increase
      the availability of effective therapy for urethritis in male patients. OBJECTIVE:
      To evaluate a pilot project of social marketing of urethritis treatment packages.
      The project, initially designed for over the counter sale in private pharmacies,
      was finally restricted by national health authorities to primary healthcare
      settings in Yaounde and Douala, Cameroon. METHODS: Monthly sales of packages
      containing antibiotics, condoms, partner referral cards, and written information
      on STDs were monitored by the social marketing agency. Structured interviews were
      conducted with a sample of traceable patients who had consulted for urethritis.
      Structured interviews completed by focus group discussions were conducted among
      healthcare providers. Interview findings were further validated by a "mystery
      patient" survey, using surrogate patients. Lastly, 15 key informants among the
      decision markers involved in the project were interviewed in depth. Local
      independent consultants carried out the whole evaluation. RESULTS: A total of
      1392 treatment packages were sold in 10 months. Patients who had purchased the
      package reported high compliance with the treatment, with 99% taking the single
      dose of cefuroxime-axetil and 83% completing the course of doxycycline. 76%
      notified all or some partners, and 84% of those who had sex during treatment used
      condoms. In contrast, only 27% of trained healthcare providers prescribed
      "MSTOP". They questioned the omission of laboratory diagnosis, the selection of
      antibiotics, and the duration of therapy. Public health authorities were also
      sceptical about the choice of antibiotics and viewed the initial project as an
      overt encouragement of self medication. CONCLUSIONS: Although the MSTOP project
      was not implemented in the way it had initially been designed, it highlighted the
      patients' interest in the product. Public health authorities in Cameroon should
      have been made aware of the limitations of the formal sector's response to STD
      care among men before over the counter sale of prepackaged therapy could have
      been considered as an alternative approach to inadequate self medication.

PMID- 9924463
TI  - What about money? Effect of small monetary incentives on enrollment, retention,
      and motivation to change behaviour in an HIV/STD prevention counselling
      intervention. The Project RESPECT Study Group.
AB  - OBJECTIVES: We studied the effect of small monetary incentives and non-monetary
      incentives of similar value on enrollment and participation in clinic based
      HIV/STD prevention counselling. We examined incident STDs to try to assess
      whether participants offered money may be less motivated to change risky
      behaviours than those offered other incentives. METHODS: Patients from five US
      STD clinics were invited to enroll in a multisession risk reduction counselling
      intervention and, based on their enrollment date, were offered either $15 for
      each additional session or non-monetary incentives worth $15. The two incentive
      groups were compared on participants' enrollment, completion of intervention
      sessions, and new STDs over the 24 months after enrollment. RESULTS: Of 648
      patients offered money, 198 (31%) enrolled compared with 160 (23%) of 696
      patients offered other incentives (p = 0.002). Enrollees in the two incentive
      groups had similar baseline characteristics, including condom use. Of the 198
      participants offered money, 109 (55%) completed all sessions compared with 59
      (37%) of the participants offered other incentives (p < 0.0001). Comparing those
      offered money with those offered other incentives STD rates were similar after 6,
      12, and 24 months. CONCLUSIONS: Small monetary incentives enhanced enrollment and
      participation compared with other incentives of similar value. Regardless of
      incentive offered, participants had similar post-enrollment STD rates, suggesting
      that the type of incentive does not adversely affect motivation to change
      behaviour. Money may be useful in encouraging high risk individuals to
      participate in and complete counselling or other public health interventions.

PMID- 9924464
TI  - Managing STIs identified after testing outside genitourinary medicine
      departments: one model of care.
AB  - OBJECTIVES: To develop a local strategy for managing cases of Chlamydia
      trachomatis (CT) and Neisseria gonorrhoeae (GC) which have been identified in the
      departments of obstetrics and gynaecology (O&G). METHODS: Weekly notification
      from the local microbiology laboratory to genitourinary medicine (GUM)
      departments of all positive CT and GC results generated by tests performed in the
      two local O&G departments. Direct contact made by GUM departments to index
      patients identified and "fast track" appointments made. Data recorded for future
      audit include numbers attending, details of health adviser input, and success of
      contact tracing. RESULTS: Over 18 months, 294 women were identified and 231 (78%)
      attended GUM departments; 142 (48%) had received antibiotics before attending GUM
      departments and of these, 58 (41%) had risked reinfection by an untreated partner
      and 48 (20%) were found on screening to have a previously undiagnosed genital
      infection. Over 90% were interviewed by a health adviser. Appropriate follow up
      was achieved in 87% of index cases. Of the contacts, 194 were treated--150 in the
      local GUM department. Of these 150 men, 99 (66%) had an identifiable genital
      infection and 84% of those with CT/non-gonococcal urethritis were asymptomatic.
      There have been no complaints either formal or informal, by women managed by this
      system. CONCLUSIONS: GUM clinics are the ideal setting to achieve successful
      treatment of patients with sexually acquired infections, which must include
      notification and treatment of their partners if reinfection is to be avoided. For
      patients with infections diagnosed on other settings, such as O&G, a system of
      direct notification of results to GUM departments by an agreed protocol can be
      highly successful. For such a system to work, close cooperation and trust between
      departments is essential.

PMID- 9924465
TI  - Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses
      for discrimination of cerebral lymphoma and toxoplasmosis in AIDS.
AB  - OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and
      thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA
      detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma
      and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32
      patients infected with HIV who had focal CNS lesions on MRI as a result of either
      lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had
      toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only
      seven patients--four with toxoplasmosis, two with lymphoma, and one with both
      diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with
      lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23
      patients, appearances did not discriminate between lymphoma and toxoplasmosis;
      nine patients had single lesions, of these eight had lymphoma (p = 0.044, two
      tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma
      and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine
      patients with single lesions on MRI and 201Tl SPET with focal accumulation eight
      had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with
      lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid
      discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with
      focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI
      with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios
      less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in
      CSF is highly sensitive and specific for cerebral lymphoma.

PMID- 9924466
TI  - Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection:
      a randomised, double blind, placebo controlled trial.
AB  - BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity
      against human immunodeficiency virus (HIV), with complete inhibition of HIV
      replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan
      investigators reported that oral administration of an extremely low dose (150
      IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS
      related complex and AIDS symptoms and resolution of opportunistic infections
      without additional treatment. Moreover, loss of HIV antibody seropositivity was
      reported in approximately 10% of treated patients. Subsequent small studies
      failed to substantiate these spectacular claims, but controversy on the efficacy
      of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with
      WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50,
      who had not received any drugs with antiretroviral activity in the previous 3
      months. The patients were randomly assigned in a double blind fashion either to
      150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended
      from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112
      subjects had already received 28 weeks of treatment and been discontinued from
      the study. RESULTS: Both study groups were comparable with respect to all
      baseline characteristics studied, except that the nHuIFN-alpha group had slightly
      lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo
      group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted
      for CD4+ lymphocyte counts at entry. In both treatment groups there was
      relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and
      placebo had similar mortality, disease progression rates, decline of CD4+
      lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms.
      No patient reverted to HIV-1 seronegative antibody status. Serious adverse events
      were not seen. Quality control of the study medication documented that the active
      drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large,
      randomised, double blind, placebo controlled study did not show any benefit from
      oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients
      with symptomatic HIV infection.

PMID- 9924467
TI  - Influence of genital infection on cervical cytology.
AB  - OBJECTIVE: To ascertain whether the presence of genital infection adversely
      affects smear quality. METHOD: A prospective study of all patients having
      cytology performed. The presence of genital infection was recorded and compared
      with the smear result. RESULTS: The presence of genital infection was not
      associated with inadequate cytology. Inflammatory changes were found in
      association with symptomatic candidiasis, trichomoniasis, Chlamydia trachomatis
      infection, primary herpes simplex, and the finding of 21-30 polymorphs per high
      power field (averaged over 10 fields) on cervical samples. Inadequate cytology
      was significantly associated with the smear taker. CONCLUSION: The presence of
      genital infection at the time of cytology does not increase the rates of
      inadequacy, and opportunistic cytology should not be deferred as the patient may
      default from further appointments.

PMID- 9924468
TI  - Randomised double blind trial of EMLA for the control of pain related to
      cryotherapy in the treatment of genital HPV lesions.
AB  - OBJECTIVE: To evaluate the efficacy of EMLA (eutectic mixture of local
      anaesthetic) for the control of pain related to cryotherapy for the treatment of
      human papilloma virus (HPV) in the outpatient setting. DESIGN: A randomised,
      double blind, placebo controlled study. SUBJECTS: 40 patients (20 male and 20
      female) with external genital HPV involving an area of no greater than 1 cm2.
      SETTING: The Capital Health Sexually Transmitted Disease Clinic, Edmonton,
      Alberta, Canada. RESULTS: Patients in whom EMLA was utilised reported
      significantly lower scores than those in the control group. Women reported pain
      scores of 4.7/10 and 0.9/10 in placebo and EMLA groups respectively (p < 0.01).
      Men reported pain scores of 6.4/10 and 3.1/10 in placebo and EMLA groups
      respectively (p < 0.01). Men reported significantly higher pain scores than women
      in the EMLA groups (p < 0.01). There was no significant difference in pain scores
      between men and women in the placebo groups. CONCLUSION: EMLA can provide
      efficacious topical anaesthesia before cryotherapy for the treatment of external
      genital HPV.

PMID- 9924469
TI  - Periurethral gland abscess: aetiology and treatment.
AB  - OBJECTIVES: To establish some characteristics of patients with periurethral gland
      abscess, its microbiological profile, and response to treatment. METHOD: The
      patients were seen at the Khami Road Clinic, Bulawayo, a municipal STD referral
      clinic, serving an urban population. Twenty consecutive men with periurethral
      abscesses were studied. Demographic data and a sexual history were obtained from
      each patient. Aspirates from the abscess cavities and urethral swabs were
      collected for microbiology, and blood samples taken for syphilis and HIV
      serology. The patients were treated by aspiration of the abscess cavities,
      followed by a single injection of kanamycin 2.0 g followed by a 1 week course of
      oral doxycycline 100 mg twice daily. RESULTS: Neisseria gonorrhoeae was cultured
      from three aspirates and five urethral specimens. Chlamydia trachomatis was found
      in two aspirates and three urethral specimens. Other organisms isolated included
      Gram negative and anaerobic bacilli. HIV antibody was detected in 13 of 18
      patients tested. The response to initial treatment was good, but the abscesses
      ruptured in two patients, one of whom developed a urinary fistula. One patient
      required treatment with an alternative antimicrobial regimen. CONCLUSION: This
      study demonstrated a role for N gonorrhoeae and possibly for C trachomatis in the
      aetiology of periurethral abscess. The prevalence of HIV infection in these
      patients was high. The results of treatment of periurethral abscess by aspiration
      of pus and followed by antimicrobial therapy covering both N gonorrhoeae and C
      trachomatis were acceptable.

PMID- 9924471
TI  - Prospective cohort study of female sex workers and the risk of HIV infection in
      Alicante, Spain (1986-96).
AB  - OBJECTIVE: To measure the incidence of HIV infection over a 10 year follow up in
      a cohort of female commercial sex workers in Alicante (Spain), and to determine
      factors associated with high risk of infection. METHODS: A prospective cohort
      study was carried in an AIDS information and prevention centre in Alicante,
      Spain. Of the 1388 female sex workers who initially sought the services of the
      centre since September 1986, 657 completed at least one additional follow up
      visit before December 1996. Main outcome measures were infection with HIV-1 and
      reported risk behaviours. RESULTS: During 1815 person years of observation among
      657 female sex workers who were free of HIV infection (negative test), 16 women
      developed of HIV infection (incidence rate of HIV infection = 8.8 cases/1000
      woman years, 95% confidence interval (CI): 5.4-14.4). Reported current use of
      injecting drugs at the first visit was associated with an increased risk of HIV
      infection (relative risk, RR = 12.87, 95% CI: 4.81-34.15) as well as having an
      usual partner with injecting drug addiction (RR = 20.89, 95% CI: 7.44-58.70).
      Infection also was associated with younger age (RR for 1 year = 0.86, 95% CI:
      0.76-0.96). After multivariate adjustment using Poisson regression analysis, the
      factors that remained significantly associated with the risk of HIV infection
      were current use of injecting drugs (RR = 4.61, 95% CI: 1.37-15.46), and having a
      usual partner with injecting drug addiction (RR = 10.08, 95% CI: 2.94-34.57).
      There was also some evidence that a younger age could be related to infection.
      CONCLUSION: These data suggest that the risk of HIV infection among this cohort
      of female sex workers in Alicante is predominately associated with the use of
      injecting drugs, and having a regular partner with injecting drug addiction. An
      increasing number of clients did not play a role in the risk of infection.

PMID- 9924470
TI  - Isolation and characterisation of T lymphocytes from the urethra of patients with
      acute urethritis.
AB  - OBJECTIVES: To investigate local cellular immune responses in patients with acute
      urethritis. METHODS: We have established T cell lines from the urethral exudate
      and examined their phenotype by flow cytometry. As controls, T cell lines were
      cultured from first pass urine specimens of asymptomatic healthy individuals.
      RESULTS: Using interleukin 2 (IL-2) alone a T cell line was obtained on only one
      occasion. Following culture with IL-2, and subsequent expansion by a single
      stimulation with irradiated allogenic peripheral blood mononuclear cells (PBMC),
      phytohaemagglutinin (PHA), and IL-2, it was possible to establish T cell lines
      from 6/6 acute urethritis patients. T cell lines were also obtained from 4/12
      controls subjects, but required repetitive rounds of stimulation with mitogen and
      allogeneic PBMC to produce sufficient cell numbers for analysis. Three of the
      patient T cell lines were dominated by T cells expressing the gamma delta
      receptor. CONCLUSION: The gamma delta T cell subset has been associated with
      immune responses at mucosal surfaces and has the ability to recognise certain
      bacterial antigens. The gamma delta T cell response may represent an important
      aspect of the immune response to organisms associated with acute urethritis.

PMID- 9924473
TI  - In vitro activity of several antimicrobial agents against Neisseria gonorrhoeae
      in the western region of the Kingdom of Saudi Arabia.

PMID- 9924472
TI  - Detection of Chlamydia trachomatis in genital swabs: comparison of commercial and
      in house amplification methods with culture.
AB  - AIMS: To evaluate the sensitivity of the Roche Cobas, Roche Amplicor plate kit,
      ligase chain reaction (LCR), and an in house polymerase chain reaction (PCR) by
      titration of purified elementary bodies (EB) and also to test 245 urethral and
      endocervical specimens for Chlamydia trachomatis by the four assays as well as
      conventional culture. STUDY DESIGN: EB titrations were run in duplicate in each
      commercial assay and six times in the in house PCR. Clinical samples were
      aliquoted and tested by each assay and were considered positive if C trachomatis
      was detected by two or more separate tests or if the sample was either culture or
      immunofluorescence positive. Major outer membrane protein (MOMP) specific primers
      were used as a confirmatory assay for the in house PCR. RESULTS: The in house
      PCR, Roche Cobas Amplicor, LCR, and Amplicor plate kit gave detection limits of
      approximately 1, 1-2, 2, and 2-4 EBs respectively. By the criteria described
      above for definition of a C trachomatis positive result in clinical samples we
      identified 23 true positives among the 245 clinical specimens. The in house PCR
      detected all 23 giving a sensitivity of 100% and a specificity of 98%. The Roche
      Cobas Amplicor, Roche Amplicor plate kit, and LCR detected 21, 19, and 19 of
      these respectively giving sensitivities of 87.5%, 82%, and 82% respectively and
      specificities of 99.5%, 99%, and 100% respectively. The culture gave a
      sensitivity of 78% and specificity of 100%. CONCLUSION: All four amplification
      assays had a greater sensitivity than the culture used routinely in this
      laboratory. The in house plasmid PCR had the greatest sensitivity and when
      combined with confirmation by immunofluorescence detected the greatest number of
      positives. This increased sensitivity is likely to have been achieved by the use
      of a DNA purification step and of nested primers in the amplification stage and
      their combined use in routine diagnostic assays for chlamydia might increase the
      frequency of C trachomatis detections. However, this assay is much less user
      friendly than the two semiautomated commercial assays investigated in this study.

PMID- 9924474
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from men with
      urethritis in Kenya.

PMID- 9924475
TI  - Genital ulcers associated with acute Epstein-Barr virus infection.
AB  - To date there have been only five reported cases of females with genital
      ulceration associated with primary Epstein-Barr virus infection. We describe two
      further patients and review the clinical features of all seven cases, noting the
      typical features, particularly purple ulcer margins and systemic symptoms, which
      should alert the physician to consider this diagnosis.

PMID- 9924476
TI  - Extragenital donovanosis of the foot.
AB  - An extremely rare case of primary extragenital donovanosis affecting the dorsa of
      right foot is reported. Clinical and histopathological features of the disease
      are described and the rarity, absence of genital lesions, and consequent
      difficulty in diagnosis are discussed.

PMID- 9924477
TI  - HPV testing in cervical screening.

PMID- 9924478
TI  - Lymphangioma circumscriptum of the penis.

PMID- 9924479
TI  - Post-exposure prophylaxis (PEP) after non-occupational risk of HIV infection.

PMID- 9924480
TI  - Outbreak of hepatitis A in homosexual men in Riverside.

PMID- 9924482
TI  - Erectile Dysfunction Alliance.

PMID- 9924481
TI  - Prevalence of sexually transmitted diseases in pregnant women in Suva, Fiji.

PMID- 9924483
TI  - Mycobacterium genavense infection in a UK based patient with AIDS: diagnosis
      using molecular techniques.

PMID- 9924484
TI  - Heterosexual transmission of HIV in Scotland.

PMID- 9924485
TI  - Epithelial ovarian cancer.

PMID- 9924486
TI  - Tamoxifen for prevention of breast cancer.

PMID- 9924487
TI  - Growth-hormone-releasing factor for growth hormone deficiency.

PMID- 9924488
TI  - Palivizumab (Synagis) for prevention of RSV infection.

PMID- 9924489
TI  - How to safeguard your clinical data. Security systems against crashes, thieves,
      and hackers.

PMID- 9924490
TI  - Echocardiography for mitral valve prolapse?

PMID- 9924491
TI  - Going solo.

PMID- 9924492
TI  - Carbon monoxide poisoning. Early awareness and intervention can save lives.
AB  - Each year, particularly during the heating season, thousands of people are
      poisoned by carbon monoxide, with potentially devastating outcomes. Initial
      diagnosis can be difficult because symptoms closely resemble those of influenza
      and are often misinterpreted. Dr Tomaszewski discusses diagnosis and treatment,
      including the benefits and risks of hyperbaric oxygen therapy.

PMID- 9924493
TI  - Recognizing atypical manifestations of GERD. Asthma, chest pain, and
      otolaryngologic disorders may be due to reflux.
AB  - The presence of common symptoms, such as heartburn and regurgitation, usually
      make the diagnosis of gastroesophageal reflux disease (GERD) fairly
      straightforward. However, extraesophageal symptoms of GERD, such as asthma,
      noncardiac chest pain, and hoarseness, are often not recognized and therefore are
      poorly managed. This article sheds light on the atypical manifestations of GERD
      as well as current approaches to diagnosis and treatment.

PMID- 9924494
TI  - Cold injuries. Protecting your patients from the dangers of hypothermia and
      frostbite.
AB  - Hypothermia may occur in any part of the country but is an especially important
      concern among people who enjoy cold weather sports. Prompt recognition and
      treatment are paramount, since many hypothermia victims have recovered from very
      low body temperatures. Therefore, even if someone appears to be dead from
      exposure to cold, resuscitative efforts should be started and continued until the
      proper core body temperature is reached. Although frostbite is often considered
      minor, it can cause permanent tissue damage. Preparation is the key to protecting
      patients from the effects of cold weather, and frostbite, frostnip, and
      hypothermia should always be taken seriously. Treatment in a medical facility can
      make the difference between full recovery and lifelong problems.

PMID- 9924495
TI  - The downside of snowboarding. Common injuries in novices and those seeking
      'hospital air'.
AB  - Depending on where you live, you may never have treated a snowboarding injury.
      However, some of your patients (or maybe your own children) may return from a
      vacation in the Rockies sporting a snowboarding injury and needing immediate
      treatment or follow-up care. How familiar are you with the injury patterns
      specific to this increasingly popular sport? Read on for an introduction to the
      world of snowboarding and helpful guidelines on how to recognize and treat common
      snowboarding injuries.

PMID- 9924496
TI  - Injuries in cross-country skiing. Trail markers for diagnosis and treatment.
AB  - Cross-country skiers can suffer acute injuries, such as sprains of the ulnar
      collateral ligament of the thumb, the medial collateral ligament of the knee, and
      the ankle. They are also subject to overuse injuries, including arthritic changes
      in the great toe, and are at risk for cold-related injuries. Most of these
      injuries can be treated conservatively, and some can be avoided with adequate
      preparation and training.

PMID- 9924497
TI  - Invasion of the fleshy papules. Syringomas.

PMID- 9924498
TI  - What's new in Alzheimer's disease treatment? Reasons for optimism about future
      pharmacologic options.
AB  - There is reason for optimism about future treatment options for Alzheimer's
      disease, despite uncertainties about which subgroups of patients will respond to
      treatment, the magnitude of therapeutic effects, the duration of benefit, and the
      long-term outcomes from disease-modifying agents. Because Alzheimer's disease is
      a heterogeneous disorder, the range of treatment responses likely will remain
      variable. The decision to initiate treatment must be individualized to the
      therapeutic goals of the patient and his or her caregiver. Advances in the
      understanding of the pathogenesis of Alzheimer's disease have led to new
      treatment strategies. Augmentation of cholinergic function through the use of
      acetylcholinesterase inhibitors with favorable side-effect profiles (e.g.,
      donepezil, possibly metrifonate) can create the potential for improved memory and
      cognition. Antiinflammatory drugs, estrogen, alpha-tocopherol, selegiline, and
      ginkgo biloba are the subject of ongoing clinical trials to determine their
      effectiveness in Alzheimer's disease. Future treatment strategies will likely
      include a combination of acetylcholinesterase inhibitors and disease-modifying
      agents. A greater understanding of the pathogenesis of Alzheimer's disease may
      lead to the development of new neuroprotective agents. The long-term human and
      social costs, as well as potential benefits, of prolonging the natural course of
      the disease can only become evident with study of these agents in years to come.

PMID- 9924499
TI  - Management of type 2 diabetes mellitus. Institute for Clinical Systems
      Integration.

PMID- 9924500
TI  - Violence in the emergency department. Managing aggressive patients in a high
      stress environment.

PMID- 9924501
TI  - How to resolve stool retention in a child. Underwear soiling is not a behavior
      problem.
AB  - Many parents do not realize their child has stool retention when they bring him
      or her for an office visit. Some complaints that may be a tip-off and should
      prompt questioning about stool frequency and underwear soiling are vague
      abdominal pain, urinary incontinence, and stools so large they plug the toilet. A
      rectal examination is usually adequate to confirm the diagnosis. Management
      begins with educating parents that leaking of liquid stool around impaction and
      onto underwear is completely involuntary, so the child should never be scolded or
      embarrassed. Stool retention may begin because of unpleasant or unavailable
      toilet facilities, constipation, or painful elimination and often becomes self
      perpetuating. Impaction must be removed immediately; magnesium citrate solution
      is usually effective. To allow the rectum to return to its normal size, which can
      take an extended time, stool must be kept soft and movable with administration of
      mineral oil and appropriate dietary choices (eg, fruit, juice, fiber). Recurrence
      is common, so ongoing measures and follow-up are important.

PMID- 9924502
TI  - How to spot scabies in infants.

PMID- 9924503
TI  - Playing it safe in winter.
AB  - Outdoor activities can be an exciting part of winter, provided you are prepared
      and can protect yourself from cold, windy, and wet conditions. Remember that
      temperatures need not be extremely low for injuries to occur, and even people
      living in warm climates are vulnerable to "exposure." Young age, old age,
      physical problems, and medications also play a role. Here is some information to
      help you stay safe.

PMID- 9924504
TI  - [Public laboratories for vaccine production: a new paradigm].
AB  - In Latin America and the Caribbean, public laboratories that produce vaccines
      have contributed in varying degrees to the control and eradication of vaccine
      preventable diseases, and several of them are manufacturing vaccines that are
      routinely applied in national immunization programs, such as the vaccine against
      tuberculosis (made with the bacillus of Calmette-Guerin, BCG), the triple vaccine
      against diphtheriatetanus-pertussis (DTP), tetanus toxoid (TT), the vaccine
      against measles and the oral vaccine against polio. Thanks to recent scientific
      strides, one can foresee an important increase in the number of safe and
      effective vaccines that will be available in the near future for use in routine
      vaccination programs. However, there are high costs involved in developing such
      vaccines and in protecting the intellectual property rights involved, and few
      laboratories in Latin America have the technical capacity to research and develop
      these vaccines. Such factors will affect the speed with which they are
      assimilated into vaccination programs in countries of the Region. Currently,
      public laboratories that manufacture vaccines in the Region are not equipped to
      compete in this new scenario and run the risk of being completely outmarketed.
      Thus, they must radically change their style of management and their scientific
      and technical capabilities, backed by a commitment from governments to improve
      and strengthen those political and financial aspects that can assure that
      national laboratories participate in the sustainable supply of vaccines to
      immunization programs, as well as in researching, developing, and producing new
      vaccines.

PMID- 9924505
TI  - Stroke in Trinidad and Tobago: burden of illness and risk factors.
AB  - This study describes the burden of stroke on hospital services in a Caribbean
      community. The settings are the two main acute general hospitals in Trinidad
      observed over a 12-month period. All subjects were admitted with a clinical
      diagnosis of acute stroke. The measures were hospital admission rates, length of
      hospital stay, case-fatality rates, disability at discharge, and risk factors for
      stroke. There were 1,105 hospital admissions with a diagnosis of stroke. The
      median length of stay was 4 days, with an interquartile range of 2 to 9, and
      stroke accounted for approximately 9,478 bed days per annum. The hospital
      admission fatality rate was 29%. Among surviving patients, 437 (56%) were
      severely disabled at discharge. Age-standardized admission rates for first
      strokes in persons aged 35-64 years were 114 (95% CI: 83 to 145) per 100,000 in
      Afro-Trinidadian men and 144 (109 to 179) in Indo-Trinidadian men. The equivalent
      rates for women were 115 (84 to 146) and 152 (118 to 186). Among patients with
      first strokes, 348/531 (66%) reported physician-diagnosed hypertension, but only
      226 (65%) of these reported being on antihypertensives at admission. Stroke in
      Trinidad and Tobago is associated with a high case-fatality rate and severe
      disability in survivors. Modifiable risk factors were reported in a majority of
      stroke cases, and there is a need to develop effective preventive strategies.

PMID- 9924506
TI  - [Analysis of fluoride concentration in mineral waters in the Araraquara region in
      Brazil].
AB  - It has been shown that people of all ages can benefit from the topical and
      systemic effects of water fluoridation. However, the increase in consumption of
      bottled water, either to substitute for or supplement consumption of water from
      public sources, has implications for safe fluoride supplementation. Taking that
      into consideration, in 1995 we analyzed the fluoride content in 31 commercial
      brands of mineral water in the region of Araraquara, state of Sao Paulo, Brazil.
      Fluoride concentration as determined by our analysis was compared to the
      concentration of fluoride specified on each label. Only 25% of the products
      studied listed the fluoride concentration on their labels. In addition, among 31
      mineral water brands, 26 listed the date when the chemical analysis to determine
      chemical composition had been performed. Of these, 20 had not been put through
      the annual chemical analysis determined by Brazilian law. Based on these results,
      if the mineral waters tested had been the only source of drinking water, fluoride
      supplementation would have been necessary in 69% of the samples analyzed. In the
      case of children up to 6 years of age who use products containing fluoride, such
      as topical gels, mouthwashes or toothpastes, supplementation should be
      recommended only if commercially bottled water is the only source of water used,
      not only for drinking but for cooking as well.

PMID- 9924507
TI  - Spatial distribution of insecticide resistance in Caribbean populations of Aedes
      aegypti and its significance.
AB  - To monitor resistance to insecticides, bioassays were performed on 102 strains of
      the dengue vector Aedes aegypti (L.) from 16 countries ranging from Suriname in
      South America and through the chain of Caribbean Islands to the Bahamas, where
      the larvicide temephos and the adulticide malathion have been in use for 15 to 30
      years. There was wide variation in the sensitivity to the larvicide in mosquito
      populations within and among countries. Mosquito strains in some countries such
      as Antigua, St. Lucia, and Tortola had consistently high resistance ratios (RR)
      to temephos, ranging from 5.3 to 17.7. In another group of countries--e.g.,
      Anguilla and Curacao--mosquitoes had mixed levels of resistance to temephos (RR =
      2.5-10.6), and in a third group of countries, including St. Kitts, Barbados,
      Jamaica, and Suriname, mosquitoes had consistently low levels of resistance to
      temephos (RR = 1-4.6) (P < 0.05). On occasion significantly different levels of
      resistance were recorded from neighboring A. aegypti communities, which suggests
      there is little genetic exchange among populations. The impact of larval
      resistance expressed itself as reduced efficacy of temephos to kill mosquitoes
      when strains were treated in the laboratory or in the field in large container
      environments with recommended dosages. Although a sensitive strain continued to
      be completely controlled for up to 7 weeks, the most resistant strains had 24%
      survival after the first week. By week 6, 60% to 75% of all resistant strains of
      larvae were surviving the larval period. Responses to malathion in adult A.
      aegypti varied from a sensitive population in Suriname (RR = 1.3) to resistant
      strains in St. Vincent (RR = 4.4), Dominica (RR = 4.2), and Trinidad (RR = 4.0);
      however, resistance was generally not on the scale of that observed to temephos
      in the larval stages and had increased only slightly when compared to the levels
      that existed 3 to 4 years ago. Suggestions are made for a pesticide usage policy
      for the Caribbean region, with modifications for individual countries. This would
      be formulated based on each country's insecticide-resistance profile. Use of
      physical and biological control strategies would play a more critical role than
      the use of insecticides.

PMID- 9924508
TI  - [Resurgence of the measles epidemic: situation in Minas Gerais, Brazil].
AB  - This study aims to describe the measles vaccination campaigns that have been
      carried out in the state of Minas Gerais, Brazil, since 1988; to highlight their
      importance in the control of the disease, and to pinpoint the age groups at risk
      during the recent epidemic, which began in 1996, spread all over the country, and
      declined in 1998. However, the analysis includes only data up to September 1997.
      The methodology used was based on the birth cohort analysis design. Data compared
      by cohorts included target population and vaccination coverage for each campaign,
      and measles incidence rates during the present epidemic. Results show that the
      more opportunities for exposure to vaccination campaigns, the lesser the risk for
      having measles in any birth cohort. In 1997, the relative risk for getting
      measles was 15.38 (IC 95%: 9.89 to 23.93) for the cohort under 2 years of age,
      which had not had the opportunity to be exposed to any vaccination campaigns, as
      compared to cohorts between 3 and 19 years of age with two or more opportunities
      of exposure to vaccination campaigns. On the basis of the experiences analyzed,
      catch-up measles vaccination campaigns as well as follow-up campaigns-
      particularly when routine vaccination did not achieve sufficient coverage--have
      had an outstanding role in controlling the measles epidemic in the state of Minas
      Gerais. We therefore suggest making the measles vaccine immediately available to
      all birth cohorts that did not have the opportunity for exposure to past
      vaccination campaigns and intensifying epidemiological surveillance. Moreover, it
      is necessary to find ways to improve routine vaccination coverage in order to
      achieve the 95% goal set by the National Plan to Eliminate Measles by the Year
      2000.

PMID- 9924509
TI  - [The World Health Organization is 50 years old].
AB  - In celebration of the World Health Organization's 50th anniversary, this article
      features WHO's contribution to the world by examining its current activities in
      the areas of health, human rights, and development. It briefly summarizes events
      leading to its establishment over the period from 1851 to 1948, which marks the
      year when WHO assumed its role as a specialized body of the United Nations.
      Quoting from various articles in WHO's Constitution, it illustrates the
      principles that prompt its actions and that have led nations to become aware of
      their potential goals, thus steering them toward a brighter future. A brief
      overview of the last 20 years ends with the introduction of WHO's new Director
      General, Dr. Gro Harlem Brundtland.

PMID- 9924510
TI  - Safe Motherhood 2000 programs: objective, design, and evaluation.

PMID- 9924511
TI  - [Environmental primary care for the 21st century].
AB  - Primary environmental care combines the original strategy proclaimed at Alma-Ata
      as primary health care and the conception of integral rural development that
      emerged from the agrarian policies of Third World countries during the seventies.
      Within the renewed goal of health for all in the 21st century, the primary
      environmental care strategy may be considered as all those actions necessary to
      improve and protect the local surroundings through foresight and prevention of
      possible problems, with tasks institutionalized at the local level. Analysis and
      practice of this strategy are based on a model focused on the promotion of human
      beings, the environment, and social development. Furthermore, it is founded on
      critical theory and has a holistic perspective. This operational frame encourages
      participation and action, thus endowing individuals, communities, and societies
      with the power to make decisions. In this way, leadership is created for the
      sustainable development of nations.

PMID- 9924512
TI  - [Survival of Vibrio cholerae 01 in freshwater surface and endemic cholera: a
      geological hypothesis].
AB  - The danger that cholera is becoming endemic in Latin America makes it imperative
      to know the geographic location of aquatic environments where ecological
      conditions favor long-term survival of the toxigenic Vibrio cholerae O1 El Tor
      biotype, and such aquatic environments should be sampled to determine if they
      harbor this microorganism. For efficient and effective sampling, it would be
      useful to know what kinds of waters are ecologically suitable for the survival of
      this pathogen during periods between epidemics, and where these bodies of water
      are located. This paper presents the hypothesis that toxigenic V. cholerae O1's
      ability to survive in surface freshwaters tends to be inversely related to the
      altitude above sea level of these freshwaters.

PMID- 9924513
TI  - Effectiveness of nutrition centers in Ceara state, northeastern Brazil.
AB  - Childhood malnutrition has been a major, long-standing health concern in
      northeastern Brazil. In response, during 1992-1994, the state government of
      Ceara, with financial support from the World Bank, established 34 new nutrition
      centers. During 1996 an evaluation of the centers was conducted to determine
      their effectiveness in treating children with malnutrition and to identify
      weaknesses in the system and possible solutions. Also evaluated were the adequacy
      of resources, admission and discharge criteria, staff training, and community
      satisfaction. Effectiveness was found to be low. Treatment procedures did not
      conform with World Health Organization recommendations. Rates of weight gain were
      inadequate, and the mean duration of rehabilitation--8.7 months--was too long.
      Case fatality in two centers was unacceptably high, 40% and more. Entry and exit
      criteria for rehabilitation were ill defined, resulting in some nonmalnourished
      children being enrolled. Few staff were adequately trained; knowledge was weak,
      especially about case management; and mothers were not effectively instructed.
      Recommendations include setting objectives for the centers, improving referral
      systems, standardizing entry criteria, improving case management, and
      establishing performance indicators.

PMID- 9924514
TI  - [Acute poisoning from pesticides: human and economic costs].
AB  - The use of pesticides has produced great agricultural benefits and, at the same
      time, serious public health problems that need to be solved. According to studies
      performed in the 1980s and 1990s, every year about half a million to one and a
      half million cases of acute pesticide poisoning are notified, together with 3,000
      to 28,000 deaths. The purpose of this study was to draw attention to the
      incidence of acute pesticide poisoning and to the social and economic costs that
      are attributable to pesticides in different parts of the world. We present data
      on the economic importance of the pesticide industry and describe the situation
      of acute poisonings from exposure to pesticides and consumption of contaminated
      foods. Such data show that pesticide poisonings are more frequent in developing
      countries than in industrialized countries, even though developing countries
      consume less pesticides. We also estimate the economic costs of pesticide
      poisonings and examine certain other aspects of the situation, underscoring the
      need to reduce pesticide use.

PMID- 9924515
TI  - [Opinion of medical and nursing students on the autonomy of adolescents in health
      care services].
AB  - In an effort to better understand some of the ethical and legal dilemmas that
      health professionals face in their daily activities, this study identified and
      analyzed the opinions and expectations of medical and nursing students at the
      University of Sao Paulo, Brazil, regarding the autonomy of adolescents in
      receiving health care services. Over the 1995-1996 period, interviews were done
      with students in the first and last years of their programs in the School of
      Medicine and the School of Nursing of the University of Sao Paulo. The results
      from the first-year students were compared with those of the final-year students.
      The interview questions dealt with such issues as providing medical care to
      adolescents when a parent or guardian was not present, adolescents making their
      own decisions on health care services, the confidentiality of information that
      adolescents provide, the circumstances in which that information could be given
      to parents or guardians, and situations where there were conflicts between the
      decisions of parents and adolescents. Despite variations among the opinions and
      expectations of the students, the overall results suggest that most of the
      medical and nursing students do not accept the concept of "health adulthood" or
      autonomy for adolescents and that the students instead choose to rely on current
      legal definitions of adulthood.

PMID- 9924516
TI  - [Differences in infant mortality within Bolivia].
AB  - There was an overall decrease in infant mortality in Bolivia between the national
      censuses of 1976 and of 1992. That general pattern, however, in fact conceals
      differences in trends from one department to another, as well as between urban
      and rural areas. In order to elucidate this situation, in 1996 the reducible
      differences in mortality were analyzed. This was done by comparing the infant
      mortality rate in each department of the country with the lowest rate found in
      the other departments and calculating the possible reduction if all the
      departments had had the same level of achievement. Using a similar approach,
      urban areas were compared with rural ones. The results show that in four
      departments of Bolivia (Beni, Oruro, Pando, and Potosi) the differences in
      mortality rates increased in comparison to the other departments. That is, in
      those four departments infant mortality has not fallen as much as could be
      expected given the general trends in the country. Similarly, the decline in
      infant mortality rates in the rural areas has lagged behind the decreases seen in
      urban areas. Quantifying these differences makes it possible to propose goals for
      the national policy of sustainable human development.

PMID- 9924517
TI  - Occurrence of Cryptosporidium oocysts and Giardia cysts in water supplies of San
      Pedro Sula, Honduras.
AB  - During June 1996, water supplies of the city of San Pedro Sula, Honduras, were
      sampled to obtain an assessment of Cryptosporidium oocyst and Giardia cyst
      concentrations. Each sample was concentrated and stained with an indirect
      immunofluorescent antibody, and parasites were counted through microscopic
      analysis. In three surface water supplies, Cryptosporidium oocyst concentrations
      ranged from 58 to 260 oocysts per 100 L, and Giardia cysts were present in
      concentrations ranging from 380 to 2100 cysts per 100 L. Unlike the surface water
      samples, groundwater had a higher concentration of Cryptosporidium oocysts
      (26/100 L) than Giardia cysts (6/100 L), suggesting that the groundwater aquifer
      protects the water supply more effectively from larger Giardia cysts.
      Cryptosporidium oocyst concentrations are within the typical range for surface
      water supplies in North America whereas Giardia cyst concentrations are elevated.
      Efforts should be made to protect raw water from sources of contamination.

PMID- 9924518
TI  - [Burns: characteristics of cases treated in a teaching hospital in Ribeirao Preto
      (Sao Paulo), Brazil].
AB  - Burns are a significant health problem in Brazil, but there have been few data
      collected that could shape treatment and prevention programs. To help overcome
      that knowledge gap, this study looked at the types of accidents and the
      characteristics of 138 burn patients admitted into the burn unit of the
      University of Sao Paulo Hospital in Ribeirao Preto, state of Sao Paulo, Brazil,
      between November, 1991, and December, 1993. Patient charts were reviewed to
      collect data on age, sex, region of the body affected, burn depth and surface
      affected, agent causing the burn, and circumstances in which the burn happened.
      Of the 138 cases, 71% occurred in the home. In 50% of all accidents the victims
      were children. Boiling water was the agent responsible for 59% of the accidents
      among children younger than 3 years of age; fuel alcohol used in the home for
      cooking and other purposes caused 57% of the accidents among children between 7
      and 11 years, the most affected pediatric group. Among adults, the group between
      20 and 39 years of age was the most affected (23%); 84% of the victims in this
      age group were male. Seventeen percent of all cases involved adult males at work.
      Women suffered burns in accidents at home (67%) and in suicide-related events
      (33%). Seventy-five percent of the suicide cases were women. The strategies to
      reduce the incidence of burn injuries should aim at eliminating environmental
      risk factors and implementing educational programs disseminated through radio and
      television.

PMID- 9924519
TI  - Influenza virus epidemiological surveillance in Argentina, 1987-1993, with
      molecular characterization of 1990 and 1993 isolates.
AB  - This report describes findings from epidemiological surveillance of influenza
      virus in two cities in Argentina (Mar del Plata and Cordoba) from 1987 to 1993.
      It includes information on reporting and serologic characterization of isolated
      influenza viruses. In addition, determination was made of the nucleotide
      sequences of the HA1 subunits of five type A (subtype H3) viral strains isolated
      in the epidemics of 1990 and 1993. The incidence of illness, type of viruses
      isolated, and H gene sequences were similar to what has been reported from other
      parts of the world during the same period. The H3 strains isolated in the 1990
      and 1993 seasons were somewhat removed in their molecular characteristics from
      the strains the World Health Organization recommended for vaccines for those
      years, and appeared closer to the strains recommended for vaccination in
      subsequent seasons.

PMID- 9924520
TI  - [Sessions of clinical anatomy in Mexico at the dawn of the 21st century].
AB  - The authors present a defense of postmortem clinical anatomy sessions, which
      contributed enormously to the development of clinical medicine but which today
      draw little interest in medical studies. Nevertheless, the sessions still provide
      an unrivalled exercise in diagnosis for medical students and an excellent method
      of continuing education for practicing professionals. Autopsies make it possible
      to confirm or correct clinical diagnoses, including those obtained through highly
      complex technological procedures; they contribute to the discovery of new
      diseases and other abnormalities; they promote research; they provide reliable
      statistics on morbidity and mortality; they produce useful genetic information;
      they facilitate interdisciplinary discussion and knowledge exchange; and they can
      serve as an indicator of the quality of medical care. The authors recommend
      reviving the high academic standards of postmortem clinical anatomy sessions and
      urge professionals in health institutions to contribute as much as possible to
      the continuation and improvement of these sessions.

PMID- 9924521
TI  - Underlying reasons for sexual conduct and condom use among expatriates posted in
      AIDS endemic areas.
AB  - Among people who work abroad, sexual activity and therefore the risk of HIV
      infection appear to be relatively high. Little is known about the factors that
      influence sexual conduct when staying abroad, separated from their usual social
      environment. This is why 55 expatriates who had been sexually active in AIDS
      endemic areas were selected for an in-depth interview from the original sample of
      864 Dutch expatriates participating in a study on sexual behaviour and HIV
      infection. The social and cultural context in which the sexual contacts took
      place was addressed in these interviews. Qualitative analysis of the data led to
      the identification of four styles with regard to the meaning of and motivations
      for having sex abroad: 'the unprepared', 'the fanatical', 'the unaffected' and
      'the slightly accessible'. These styles are described separately and attention is
      paid to the association of these styles with protection behavior.

PMID- 9924522
TI  - Sexual behaviour and condom use in the general population of Spain, 1996.
AB  - A national household survey of a representative sample of 9,984 individuals aged
      15 years or over, carried out in 1996 using a combination of face-to-face
      interviews and self-completion questionnaires, was analyzed in order to describe
      the frequency of HIV sexual risk behaviours and condom use in Spain. Of a total
      of 8,101 persons (81%) who completed the questionnaire, 37% reported no sexual
      partner during the previous 12 months, 57% reported one partner and 6% reported
      more than one partner. Three per cent reported engaging in HIV sexual risk
      behaviour (i.e. more than one partner and failure to use a condom
      systematically), a pattern of behaviour which showed independent positive
      association with the male sex, an age of 20-59 years and being unmarried. Among
      those who had casual sexual partners during the preceding 12 months, 38% had
      always used condoms. In the multivariate analysis, failure to use a condom
      systematically with casual partners was associated with a higher age and being
      married. Of those who had regular partners during the previous 12 months, 26% had
      always used condoms, a finding associated with a lower age, higher educational
      level, unmarried status and non-cohabitation with the sexual partner. This survey
      has furnished some useful indicators for prevention purposes. Periodic repetition
      of this survey would enable possible changes in sexual risk behaviours to be
      detected.

PMID- 9924523
TI  - Cultures of sexual adventurism as markers of HIV seroconversion: a case control
      study in a cohort of Sydney gay men.
AB  - A case control analysis within an ongoing cohort study was used to examine
      differences between seroconverters and men who remained HIV-negative. The cases
      were interviewed within one to 13 months prior to their seroconversion. Their
      responses to a structured questionnaire were compared with those of HIV-negative
      controls drawn from the same time period and from the same longitudinal study,
      Sydney Men and Sexual Health. Data collected from both cases and controls
      included: demographic and contextual variables, knowledge of HIV transmission,
      sexual practices, drug and alcohol use and attitudinal factors. The aim was to
      compare the sexual behaviours, and the social and cultural contexts of such
      behaviours, of men prior to their HIV seroconversion with men who did not
      seroconvert. Twenty-three men had seroconverted within the cohort. Cases were
      identified by a positive HIV antibody test or self-report of positive HIV status
      following a previous negative HIV test. Three-hundred-and-sixty-nine controls
      were selected on the basis of being HIV negative at interview in 1994, and having
      at least one subsequent medically-confirmed negative HIV antibody test.
      Univariate predictors of seroconversion were: being in a regular relationship
      with a known HIV-positive partner, drug use, and engaging in a range of anal and
      esoteric sexual practices. Practices commonly used to enhance sexual pleasure,
      such as group sex, watching and being watched having sex, the use of sex toys and
      dressing up/fantasy, were engaged in more frequently by seroconverters. Engaging
      in these esoteric sexual practices was highly correlated with drug use,
      involvement in the gay community and engagement in a wide range of anal
      practices. In the multivariate analysis independent predictors of seroconversion
      were: younger age; being in a regular relationship with a known HIV-positive
      partner; believing withdrawal to be safe with regard to HIV transmission; and
      range of esoteric practices. These results indicate the importance of the social
      and cultural contexts of particular sexual practices and consequent HIV
      transmission. Sexually adventurous men may be at increased risk for HIV because
      they seek sex within particular sexual sub-cultures.

PMID- 9924524
TI  - Community pharmacist perspectives on HIV/AIDS and interventions for injection
      drug users in Canada.
AB  - In several countries, community pharmacies play a major role in the provision of
      HIV prevention services to injection drug users (IDUs). In this study, results
      from a national Canadian Survey of Community Pharmacies and HIV/AIDS Prevention
      are used to describe pharmacists' perspectives on HIV/AIDS and services to IDUs,
      and explore the relationship between personal and organizational characteristics
      and the level of support for HIV/AIDS prevention initiatives. A mailed
      questionnaire was directed to a random sample of 2,017 pharmacist owner-managers.
      The response rate was 84.6%. Results suggest that current services to IDUs
      primarily are limited to discretionary needle and syringe sales to non-diabetics,
      with almost three-quarters supportive. Staff safety was an important
      consideration in the provision of this service (77%), while remuneration was the
      lowest (27%). Community pharmacists were most comfortable with the provision of
      counselling, advice and literature (X = 2.6) and environmental and technological
      interventions (X = 2.4) and least supportive of provision of services as part of
      a programme (X = 1.6) and legalization of drugs or prescription of methadone (X =
      1.9). Female pharmacists were more likely to support preventive measures such as
      the provision of counselling or advice, and males were more likely to promote
      legislative change. Pharmacists appear generally willing to expand their services
      in the fight against HIV/AIDS. However, it is not feasible to expect uniform
      programmes to be immediately introduced. While organizational, educational and
      policy changes may facilitate programme development, individual pharmacy and
      pharmacist discretion remains important.

PMID- 9924525
TI  - The acceptability of a computer HIV/AIDS risk assessment to not-in-treatment drug
      users.
AB  - The purpose of this paper is to report the results of a study assessing the
      acceptability of a computer HIV risk assessment instrument administered to not-in
      treatment drug users. The study asked three questions related to acceptability:
      (1) are drug users comfortable responding to HIV risk questions using the
      computer assessment; (2) do drug users feel that they possess the requisite skill
      to respond to questions using a computer; and (3) do drug users believe that the
      responses they provide using the computer assessment will remain private and
      confidential. This study differs from other assessments of the acceptability of
      computer assisted data collection in that the population of interest has only
      limited education and interaction with computers. Furthermore, the study was
      implemented under field conditions. To conduct the study, an existing HIV risk
      assessment instrument was adapted for use with the computer. Only slight
      modifications were made to the content of the instrument. To facilitate data
      collection with this population, audio enhancement and touch screen were used.
      Three scales measuring comfort, skill and perceived privacy were developed.
      Results of analysis showed that drug users are comfortable responding to an HIV
      risk assessment using computer assisted interviewing. Drug users also perceived
      that they possessed the requisite skill to successfully complete the interview.
      And, study participants reported that they believed that their responses using
      the computer interview would remain private and confidential. Only minor
      differences in scale scores based on sociodemographic characteristics were found
      among study participants. Implications of the findings are discussed.

PMID- 9924526
TI  - The relative importance of factors which influence order of injecting with a
      shared needle and syringe.
AB  - Injecting drug users (IDUs) in Adelaide, South Australia, rated the likelihood of
      first use of a shared needle and syringe by persons who have characteristics
      which have previously been suggested as influencing order of injecting. This
      enabled the relative importance of these factors to be assessed. It was found
      that those who supply their own drug and injecting equipment have the greatest
      likelihood of using first, but it is also somewhat advantageous if one is able to
      promote one's needs, has recently been tested for HIV or is at home when the
      opportunity to inject arises. Older IDUs and regular users may be slightly
      advantaged, as may those who inject others and those who were denied first use
      the last time sharing occurred. A model for predicting order of use is proposed.

PMID- 9924527
TI  - The moral universe of injecting drug users in the era of AIDS: sharing injecting
      equipment and the protection of moral standing.
AB  - Recent work on HIV counselling suggests that the protection of the moral status
      of the recipient is a key factor in the successful uptake of advice. This study
      suggests it may be equally important in the uptake of health promotion messages.
      A discourse analysis of the talk of 20 young injecting drug users (IDUs)
      identified a contradiction between their asserted self-identity as careful and
      socially responsible injectors, and their admission of risky lending and
      borrowing of injecting equipment. This contradiction was resolved by the
      production of discourses of exoneration, differentially tailored to the moral
      implications of lending and of borrowing. Lenders argued a form of 'market
      morality' wherein it was the duty of each to accept the consequences of his/her
      decisions. Lenders were therefore morally exonerated since moral failure was the
      'borrowers'. Borrowing was usually depicted as 'desperate measures' for which
      moral culpability was disavowed because of 'powerlessness'. The exception of
      routine borrowing, acknowledged as risky and against community norms, was
      accounted for in a nihilistic discourse of indifference to infection and death.
      The need for a 'counter discourse' around notions of community is discussed.

PMID- 9924528
TI  - Personal social networks and HIV status among women on methadone.
AB  - This objective of this study was to examine the association between a women's HIV
      status and specific (IDUs) characteristics of her social networks with respect to
      (1) number of injection drug users (2) number of drug partners and (3) number of
      HIV-positive contacts in her personal networks, after controlling for the
      respondent's demographic characteristics and drug use. Participants were
      recruited through posted announcements in three methadone clinics in Harlem, New
      York City. Individuals were considered eligible if they were enrolled as patients
      in one of the clinics for at least three months. A social network questionnaire
      modeled after the General Social Survey network section was developed by the
      investigators. Face-to-face interviews were conducted by trained interviewers and
      included demographics, drug use, self-reported HIV status of the woman and her
      network members, and the social network structures. Univariate analyses found
      that HIV-positive and HIV-negative women had different network profiles. HIV
      positive women were more likely to associate with a higher number of current drug
      users, injection drug users, injection drug users who were HIV-positive, drug
      partners, drug partners who used injection drugs, and drug partners who were HIV
      positive. Multivariate analyses indicated that HIV-positive respondents were more
      likely to associate with HIV-positive network members than their HIV-negative
      counterparts. The findings suggest that to better understand the spread of HIV
      among female drug users and to design more effective HIV/AIDS prevention
      programmes, efforts should move beyond focusing on individual attributes to
      address the contextual dynamics of social networks.

PMID- 9924529
TI  - The cost of home-based care for HIV/AIDS patients in Zimbabwe.
AB  - From a study on the cost and quality of community home-based care (CHBC) for
      HIV/AIDS patients in Zimbabwe, programme and household costs were estimated.
      Interviews, using a structured questionnaire, were held with 60 patients and
      caregivers sampled from six types of established CHBC schemes. Detailed cost
      information was collected from four home care programmes, two urban and two
      rural. The cost of a home visit in the two urban programmes studied was estimated
      to be Z$129 (US$16) in one, and Z$183 (US$23) in the other. In one of the two
      rural schemes, the cost of a home visit was Z$313 (US$38), in the other this was
      Z$343 (US$42). A large proportion of these costs were not of direct benefit to
      the patients, as approximately 56-75% of the total cost per home visit was spent
      getting to the patient. The costs of a home visit in a rural home-based care
      programme corresponded to the costs of 2.7 inpatient days in a district hospital.
      The family cost of caring for a bedridden AIDS patient over a three-month period
      was estimated to be between Z$556-841. Caregivers spent as much as 2.5-3.5 hours
      a day on routine patient care. The programme costs are high, and schemes do not
      generally assess effectiveness, nor cost-effectiveness. The high cost of home
      visits leads to less frequent visits, leaving a larger part of both the burden
      and the cost of care to the families and the patients.

PMID- 9924530
TI  - Medications used for paediatric HIV infection in the USA, 1991-1992.
AB  - Medications constituted the third largest health care expenditure for children
      infected with the human immunodeficiency virus (HIV). Previous literature had not
      investigated volume or cost of pharmaceuticals consumed by individual patients.
      The US Agency for Health Care Policy & Research (AHCPR) therefore sponsored the
      AIDS Cost & Services Utilization Survey (ACSUS) to measure utilization of health
      care services, including medications. Starting in 1991, it surveyed 100 children
      with AIDS and 41 HIV-infected children (via adult proxies) six times at quarterly
      intervals and collected their outpatient bills. These children reported using
      5,634 prescriptions and had 5,026 bills. Children with AIDS reported more
      prescriptions than HIV-infected children. On the basis of CD4 counts and age,
      14.2% of children had indications for antiretrovirals, but did not receive them;
      and 17.7% warranted PCP prophylaxis but did not receive it. Outpatient bills
      averaged $2,325 and inpatient bills averaged $7,725 per year. These amounts
      projected nationally to $48.2 million annually, mostly paid by Medicaid.

PMID- 9924531
TI  - WHO Global AIDS statistics.

PMID- 9924532
TI  - Malaria and anaemia at different altitudes in the Muheza district of Tanzania:
      childhood morbidity in relation to level of exposure to infection.
AB  - Parallel monthly surveys of children aged 6-71 months were conducted in the
      Muheza district of Tanzania. The aim was to compare highland villages, where the
      mean, annual entomological inoculation rate (EIR) for malaria is 34 and mean
      annual prevalences of parasitaemia range from 33%-76%, with culturally similar
      villages of the lowlands, where the mean EIR is 405 and prevalences of
      parasitaemia range from 80%-84%. The total survey population could be divided
      into six geographical subgroups, which can be arranged in order of increasing
      prevalence of parasitaemia. The prevalences of dense parasitaemia, of febrile
      malaria, and of anaemia all increased in the same order across this series of
      groups, the trends being statistically significant. The results of previous
      studies have indicated a paradoxical effect whereby children in regions with a
      lower exposure to malarial infection suffer, in the long term, a higher incidence
      of severe attacks of malaria. In the present study there was no sign of any such
      paradoxical inverse relationship between the level of exposure and the prevalence
      of malarial illness or anaemia. However, child mortality rates are similar in the
      highlands and lowlands, as are the median ages of children admitted to hospital.
      Overall, the present findings indicate that, for the populations studied, an
      artificial reduction in EIR would be beneficial, even in the long term, with
      regard to the chronic effects of malaria. This does not necessarily conflict with
      previous studies reporting opposite conclusions with regard to the incidence of
      severe,acute effects.

PMID- 9924533
TI  - Treatment of antimony-unresponsive Indian visceral leishmaniasis with ultra-short
      courses of amphotericin-B-lipid complex.
AB  - High cost is the principal drawback of treating visceral leishmaniasis (VL; kala
      azar) with any of the new lipid formulations of amphotericin B. The aim of the
      present study was to see if the costs of treatment with such drugs could be
      reduced by using ultra-short courses. Amphotericin-B-lipid complex (ABLC) was
      given to 77 Indian patients with antimony-unresponsive VL, either as a single
      infusion of 5 mg/kg (Group A) or two infusions, each of 5 mg/kg, given 5 days
      apart (Group B) or on consecutive days (Group C). Other than the anticipated
      higher fever and chills, treatment was well-tolerated. On day 19 after first
      infusion, 72 patients were considered apparent cures: 24 (89%) of the 27 in Group
      A; all 24 (100%) in Group B; and 24 (92%) of the 26 patients in Group C. Six
      months after treatment, 19 (70%) of 27 in Group A, 19 (79%) of 24 in Group B, and
      21 (81%) of 26 in Group C were healthy, relapse-free and considered definitive
      cures. These cure rates were not statistically different. All 18 treatment
      failures (five initial non-responders and 13 relapses) were cured after treatment
      with a 5-day course of ABLC at a higher dose (10-15 mg/kg.day). In a related
      analysis of hospital plus drug costs for treating antimony-unresponsive VL, short
      course ABLC (1-5 days) was compared with conventional amphotericin B (0.75-1.0
      mg/kg on alternate days over 30-34 days). This analysis, which included the cost
      of re-treatment, identified one short-course ABLC regimen with an overall
      estimated expense which was only modestly higher than that of amphotericin B.
      Together, the present results provide further support for the use of ABLC in the
      management of VL patients who fail antimony therapy.

PMID- 9924534
TI  - Epidemiological identification of Chinese individuals putatively susceptible or
      insusceptible to Schistosoma japonicum: a prelude to immunogenetic study of human
      resistance to Asian schistosomiasis.
AB  - An epidemiological method, field-tested in Hunan, China, to identify residents
      potentially susceptible or insusceptible to endemic schistosomiasis japonica is
      described, as a prelude to selection of subjects for immunogenetic studies. After
      an initial cross-sectional survey on two islands (Qingshan and Niangashan-
      population 2990) in 1995-1996, an informative cohort (N = 249) was selected for
      treatment and 9-month follow-up to measure exposure and re-infection. Both the
      population prevalence (15.8%) and the geometric mean intensity of infection (26.2
      eggs/g faces) indicated that the islands were moderately endemic for
      schistosomiasis. Exposure measurements revealed a strong, positive, linear
      association (r = 0.70) between daily activity diaries and direct water-contact
      observation. Individuals identified as stool-positive for schistosomiasis had
      significantly more water contact than those who were egg-negative (P = 0.03).
      Almost all (93%) of the cohort had ultrasonographic evidence of periportal
      fibrosis before treatment but in only 1.2% was this fibrosis scored > 1 in terms
      of the stages identified by the World Health Organization. At the follow-up it
      was possible to classify the 249 subjects into three, distinct, exposure
      infection epidemiological groups. The first group (N = 20) was susceptible to re
      infection and constituted 8% of the cohort. The second group (N = 61) was
      apparently insusceptible to re-infection despite the continuing high levels of
      exposure and included 24% of the cohort. The other 68% of the cohort (N = 168)
      remained uninfected but were at most only moderately exposed, or had a status
      indeterminate due to non-compliance. This epidemiological identification of
      susceptibles and insusceptibles for schistosomiasis japonica' links field and
      ongoing laboratory studies aimed at characterising the genetic and immunological
      factors associated with resistance to re-infection and/or disease.

PMID- 9924535
TI  - Morbidity induced by Schistosoma haematobium infections, as assessed by
      ultrasound before and after treatment with praziquantel, in a recently expanded
      focus (Senegal River basin).
AB  - Seven years after the completion of two dams in the Senegal River basin, 203
      individuals from four villages around Podor in the middle valley, where
      Schistosoma haematobium infections were present, were examined in June 1995. In
      December 1995 a single dose of praziquantel (40 mg/kg) was given to each of these
      subjects, who were re-examined in April 1996. Clinical and parasitological signs
      of infection were investigated at both examinations, and ultrasonography was
      performed to check for lesions of the urinary tract induced by S. haematobium. As
      uninfected controls, 200 people from four villages where S. haematobium was
      absent were similarly examined, in November 1995. Prior to treatment, bladder
      irregularities were observed in 43% of the subjects from Podor but only 6% of the
      uninfected controls. The severity of the bladder lesions visible by
      ultrasonography was significantly associated with intensity of infection, despite
      the generally low levels of infection in the subjects mean = 13.1 eggs/10 ml
      urine). Four months after treatment, however, the frequency of bladder
      irregularities among the subjects (11%) was similar to that in the uninfected
      controls and intensities of infection and other clinical signs of disease had
      also significantly declined. The prevalence of haematuria, for example, fell from
      35% pre-treatment to 10% post-treatment. The results indicate that the onset of
      S. haematobium morbidity can be relatively rapid even in areas with seasonal and
      low levels of transmission, and demonstrate that treatment to reduce morbidity in
      such areas is important and could be relatively simple and very effective.

PMID- 9924536
TI  - The use of a stereological method to estimate the volume of Schistosoma mansoni
      granulomas: the effect of zinc deficiency.
AB  - A quantitative, stereological method to assess the volume of Schistosoma mansoni
      granulomas is presented and its use demonstrated in a study of zinc-deficient
      animals. Twenty-six mice were divided into two groups, and given zinc-deficient
      or control food. After 4 weeks, the mean weight gain and thymus size were lower
      in the mice on the zinc-deficient diet. Eight mice in each group were then each
      infected with 60 S. mansoni cercariae and these mice were killed 12 weeks post
      infection. There were then more eggs in the livers of the zinc-deficient mice
      than in those of the infected controls (7400/female worm v. 3300/female worm; P =
      0.02), probably because of impaired intestinal egg expulsion and impaired
      resorption of eggs in the deficient mice. The median proportion of each liver
      occupied by granulomas was 0.11 among the zinc-deficient mice and 0.09 among the
      pair-fed, control mice (P = 0.08), and the median liver volumes were 1400 and
      1450 microliters (P = 0.49), respectively. The computed median volume of all the
      granulomas in each liver was 160 microliters in zinc-deficient and 132
      microliters in control mice (P = 0.32), while median granuloma volume per egg was
      8.6 and 8.7 nl (P = 0.93), respectively. In contrast to conventional methods,
      modern stereological methods can provide estimates of granuloma volume or
      granuloma volume fractions without any assumptions about the size, shape,
      orientation or distribution of the granulomas in the liver.

PMID- 9924537
TI  - A method to determine the coverage of ivermectin distribution in onchocerciasis
      control programmes.
AB  - Onchocerciasis is a human filarial infection responsible for an estimated 750,000
      blind and severely visually disabled people. In some African countries, this
      disease represents the main cause of blindness, with considerable socio-economic
      impact on the affected communities. Since the introduction of ivermectin as a
      microfilaricidal agent, there is hope that visual loss from onchocerciasis can be
      eliminated through community-based ivermectin-distribution programmes. The
      African Programme for Onchocerciasis Control (APOC) has now been initiated, by
      the World Health Organization and World Bank, to distribute ivermectin in 19
      African countries where onchocerciasis is endemic. Estimates of ivermectin
      coverage in distribution programmes for onchocerciasis control have so far been
      based on the number of treatments given, in any one year, to a target population.
      There is a need for a standardized method to evaluate, measure and monitor
      coverage over time. In April 1996, a cluster random-sampling method was used to
      calculate coverage with ivermectin in an urban population of 30,000 people in the
      Central African Republic. The method was adapted from that used to determine
      coverage by the WHO Expanded Programme on Immunization. It proved to be
      inexpensive and easy to perform, requiring only local equipment and personnel.
      The method used and results obtained in Bossangoa and the potential use of the
      technique in other distribution programmes are discussed.

PMID- 9924538
TI  - Microcapsule agglutination test for the diagnosis of leptospirosis in Thailand.
AB  - Sera from 82 cases of leptospirosis (confirmed by micro-agglutination tests or
      IFAT) and 108 patients with other diseases were investigated using the
      microcapsule agglutination test (MCAT) for leptospirosis. The overall sensitivity
      (90.2%), specificity (96.3%), positive predictive value (94.9%), negative
      predictive value (92.9%), and accuracy of the MCAT (93.7%) were encouraging. MCAT
      is simple, can be performed by unskilled personnel with minimum laboratory
      facilities, and produces results in 3 h. MCAT would be a reliable serodiagnostic
      test for rapidly screening individuals for leptospirosis, in various geographical
      areas of Thailand.

PMID- 9924539
TI  - Proposed standardization of assessment protocols for plant molluscicides for use
      in self-help control programmes.
AB  - Several candidate plant molluscicides have been identified for possible
      incorporation into self-help control programmes against schistosomiasis, but
      their full potential has yet to be realised. This has been, in the most part, due
      to the absence of standardized assessment and toxicity protocols, and
      subsequently the inability to register crude plant products in their country of
      origin or internationally. In an attempt to solve this dilemma, a series of
      protocols has been designed which will provide a useful standardized guideline
      for investigations into plant molluscicides, as well as precipitate moves towards
      the establishment of internationally accepted guidelines for the assessment of
      various categories of plant biopesticides. Ultimately, being able to register a
      crude plant extract will permit health organizations such as the World Health
      Organization to promote the use of such material, especially in self-help control
      programmes, thereby improving the health standards of rural communities.

PMID- 9924540
TI  - Spontaneous splenic rupture in malaria.

PMID- 9924541
TI  - Impact of the seasonal migration of labour forces on the spread of malaria.

PMID- 9924542
TI  - Cystic and alveolar echinococcosis in Turkey.
AB  - Hydatid disease due to cystic echinococcosis (CE) is one of the most important
      public-health and economic problems in Turkey. Human CE occurs throughout Turkey
      whereas alveolar echinococcosis (AE) predominantly occurs in the eastern
      Anatolian region of the country. Human AE is also endemic in eastern Azarbaijan
      and northern Iran. Reports of approximately 207 cases of AE and 21,303 cases of
      CE in Turkey were published over the periods 1962-1995 and 1987-1994,
      respectively. Most of the data on cases of hydatid disease in Turkey and the
      Middle East have been collected from hospital records.

PMID- 9924543
TI  - Quinine and mefloquine in the treatment of multidrug-resistant Plasmodium
      falciparum malaria in pregnancy.
AB  - Between 1991 and 1996, 372 pregnant women with uncomplicated, multidrug-resistant
      Plasmodium falciparum malaria, living on the western border of Thailand, were
      treated with either mefloquine (N = 194), quinine (N = 93) or both drugs (N =
      85). Antimalarial treatment was generally well tolerated; the most common side
      effects were dizziness (42%) and tinnitus (35%) following quinine, and anorexia
      (23%) and dizziness (36%) following mefloquine. In the patients treated for
      primary infections with melfloquine, 6% failed to clear their parasitaemia by day
      7 and 28% failed by day 42. The corresponding figures for quinine were 4% and
      23%, respectively. The failure rates in the 117 women treated for recrudescent
      infections were higher, the increase being significant for quinine (38%; P =
      0.03) but not for mefloquine (37%). The percentage of pregnant women who had
      patent gametocytaemia on presentation ranged from 4%-19%. Over 50% of the
      patients were anaemic (haematocrit < 30%) on presentation and 52% of those not
      anaemic on enrolment developed anaemia during follow-up. Mefloquine and quinine,
      the only antimalarials generally available for the treatment of highly drug
      resistant P. falciparum in pregnancy, give unsatisfactory treatment responses
      when used as single agents. New, safe and effective regimens are needed for the
      treatment of pregnant women with multidrug-resistant falciparum malaria.

PMID- 9924544
TI  - Status of chloroquine efficacy against falciparum malaria in the Mola area of
      Kariba district, Zimbabwe.
AB  - The therapeutic efficacy of chloroquine was assessed, during the 1997
      transmission season, using 64 cases of uncomplicated, falciparum malaria
      originating from 18 villages in the Mola area of Kariba district, Zimbabwe.
      Chloroquine effected a modest reduction in asexual parasite density and clinical
      symptoms. The mean density of asexual parasites on day 3 post-treatment was
      24.94% (95% confidence interval = 13.59%-36.30%) of that on day 0, and 78% of the
      patients followed-up for at least 1 week were free of parasitaemia on day 7.
      However, there was appreciable therapeutic failure. The early treatment failure
      rate (i.e. by day 3) was 21% and about 6% of the cases exhibited increasing
      asexual parasitaemia despite treatment. Late treatment failures (i.e. by day 14)
      occurred in 32% of the malaria cases, and 52% of the patients were ultimately
      considered failures. All the failures were successfully treated with sulfadoxine
      pyrimethamine or quinine. Chloroquine therefore has declining parasitological and
      clinical value as the first-line, presumptive treatment for uncomplicated,
      falciparum malaria in the study area, necessitating strategies to cope with
      resistant cases. The proportion of the patients failing to be treated
      successfully with chloroquine, one of the largest reported in Zimbabwe to date,
      may-force major policy reviews in the near future. It is recommended that the
      second-line antimalarial, sulfadoxine-pyrimethamine, be distributed to health
      centre level in the study area, backed up by the decentralised confirmation of
      diagnosis. Measures to deal with treatment failures at local health centres are
      proposed.

PMID- 9924546
TI  - Evaluation of dogs as sentinels of the transmission of Trypanosoma cruzi in a
      rural area of north-western Argentina.
AB  - Dogs, the main domestic reservoirs of Trypanosoma cruzi in the Argentine chaco,
      may be useful as sentinels of vector-mediated transmission of Trypanosoma cruzi
      in control programmes if canine infections acquired by all other routes could be
      excluded. In the present study, in the province of Santiago del Estero,
      Argentina, the dog populations in the neighbouring villages of Amama, Trinidad,
      Mercedes, Villa Matilde and Pampa Pozo were studied immediately before spraying
      of residual insecticides (in 1992 in Amama, Trinidad and Mercedes and 1993-1994
      in the other villages) and twice during a subsequent programme of triatomine
      surveillance (in 1994 and 1996). Overall seropositivity for Trypanosoma cruzi
      infection (i.e. the proportion of dogs found positive by at least two different
      serological tests in any one survey) steadily declined from 65% (54/83) in 1992
      to 39% (70/182) in 1994 and 15% (36/237) in 1996. No seroconversion was detected
      between the 1994 and 1996 surveys in any dog aged > 2 years. However, among the
      dogs aged < 2 years (which were born after virtual elimination of Triatoma
      infestans from the villages), seropositivity fell from 15% (12/81) in 1994 to 5%
      (6/131) in 1996. Thirteen demographic, behavioural and entomological variables
      were analysed by logistic multiple-regression analysis for their association with
      seropositivity in dogs born locally during the surveillance programme. The total
      number of Triatoma guasayana collected in the bedroom areas of the owner's house,
      having a mother which was seropositive for Trypanosoma cruzi, and the number of
      seropositive dogs with which it cohabited were all found to be significant
      predictors of seropositivity in any dog. The results are the first indication
      that Triatoma guasayana is the vector responsible for the new cases of
      Trypanosoma cruzi infection seen in dogs in domestic or peridomestic sites during
      the surveillance programme.

PMID- 9924545
TI  - The association of pallor with haemoglobin concentration and mortality in severe
      malaria.
AB  - To identify a marker associated with poor outcome in severe malaria that requires
      no technology, the relationship between the presence of pallor and mortality was
      reviewed retrospectively in 291 Zambian children with cerebral malaria. The mean
      (S.D.) haemoglobin concentration among the 222 children assessed as having pallor
      on admission was significantly lower than that among the 69 children not
      considered to have pallor [6.0 (1.9) v. 9.2 (1.6) g/dl; P < 0.0005]. Thirty-nine
      (17.6%) of the children presenting with pallor died, compared with only five
      (7.2%) of those without pallor (P = 0.036). The adjusted odds of death in
      children with pallor on admission was 2.8 times higher than that in children
      without pallor (95% confidence interval = 1.03-7.7; P = 0.044). The clinical
      observation of pallor may therefore identify children with low haemoglobin
      concentrations and a high risk of mortality. Whether mothers and village health
      workers can be taught to recognize pallor in a child with malaria and then to
      seek early medical attention will need to be determined in further studies.

PMID- 9924547
TI  - Lack of a nitric-oxide response during the course of Leishmania infantum
      infection in the golden hamster (Mesocricetus auratus), with or without treatment
      with liposomal amphotericin B.
AB  - Liver and spleen volumes and serum concentrations of nitrate (the end-product of
      NO in vivo), albumin, gamma-globulin, protein, creatine and urea were measured
      during the course of progressive infections with Leishmania infantum MON-1
      (MHOM/PR/93/CRE29) in 10 Syrian golden hamsters. Each hamster was infected by
      intraperitoneal injection with 4 x 10(7) promastigotes. Five of the infected
      animals were treated, with 6 mg liposomal amphotericin B (L-AmB)/kg given by
      intracardiac injection, on day 107 post-infection (p.i.). Compared with those in
      the uninfected hamsters used as controls, the liver volumes in the infected
      animals became significantly enlarged by day 40 p.i. (38% larger than the
      controls; P < 0.001) whereas significant enlargement of the spleen was first
      detected on day 72. Each infected animal had detectable serum levels of
      antileishmanial antibodies on day 72. There were significant elevations in gamma
      globulin concentration as early as day 40 (P < 0.05) but significant falls in
      albumin concentrations were only detected from day 107 (P < 0.001). Nitrate,
      creatinine and urea concentrations remained unchanged during the course of
      infection, even after L-AmB treatment. Serum nitrate levels were not enhanced by
      L. infantum infection nor by the L-AmB treatment which induced a 98.2% decrease
      in parasite burden. The lack of NO production in visceral leishmaniasis, with or
      without L-AmB treatment, points to the unresponsiveness of inducible nitric oxide
      synthase in this rodent model.

PMID- 9924548
TI  - Extensive genetic variation revealed in adjacent populations of the schistosome
      intermediate host Biomphalaria pfeifferi from a single river system.
AB  - Random amplified polymorphic DNA (RAPD) analysis was used to study genetic
      variation among schistosome hosts of the species Biomphalaria pfeifferi. The
      analysed snails came from 15 sites along a 6-km stretch of a Zimbabwean river,
      providing data on genetic-geographical relationships over, probably, the smallest
      scale yet studied for any snail intermediate host species. Only 6% of the DNA
      fragments were common to all snails, and snail populations as geographically
      close as 100 m were genetically distinct. The most genetically polymorphic snail
      populations were those collected within and downstream from human water-contact
      sites.

PMID- 9924549
TI  - Soil factors influencing the distribution of Oncomelania quadrasi, the
      intermediate host of Schistosoma japonicum, on Bohol Island, Philippines.
AB  - Soil conditions essential to the survival of Oncomelania quadrasi on Bohol Island
      in the Philippines were examined to clarify the factors limiting distribution of
      the snail and to develop a method for breeding large numbers of the snail in the
      laboratory. Soil samples in and around snail habitats were analysed and used for
      breeding experiments in the laboratory. Experiments using paddy soil derived from
      different parent materials revealed that the numbers of juvenile snails hatched
      varied widely between several soil samples. The best soils for reproduction
      generally had a pH of 5.6-7.9 and > 200 mg of available CaO/100 g. These soil
      factors, in addition to shade and moisture, determine the optimum conditions for
      the breeding of O. quadrasi in the field as well as in the laboratory. The
      determination of the optimum conditions for laboratory breeding of O. quadrasi
      and other intermediate snail hosts should facilitate detailed study of the hosts
      and the development of better methods to control or eradicate schistosomiasis and
      other snail-transmitted diseases.

PMID- 9924550
TI  - In-vitro uptake of ivermectin by adult male Onchocerca ochengi.
AB  - Ivermectin is not lethal to the adult worms of Onchocerca volvulus or to those of
      O. ochengi, a cattle parasite closely related to O. volvulus. Although ivermectin
      penetrates the nodules in which the adults of these nematodes live, it is not
      known what levels of the drug enter the worms. Adult male O. ochengi were
      incubated in [3H]ivermectin in a saturated solution of unlabelled ivermectin
      (11.44 microM), to measure uptake by the oral and transcuticular routes, and in
      [3H]inulin, to ascertain if oral ingestion occurs in vitro. Uptake of
      [3H]ivermectin was high [1040 disintegrations/min (d.p.m.) at 3 h, representing a
      mean total of 86 pmoles ivermectin/worm] and occurred predominantly by the
      transcuticular route. Viability of worms was not reduced by this exposure, and
      uptake continued for up to 12 h. Only low levels of [3H]inulin (four d.p.m.) were
      detected in worms, indicating that the gut is probably not functional in vitro.
      Scanning and transmission electron microscopy revealed that the epicuticle of
      both sexes had an irregular surface which was pitted with a honeycomb structure
      in males, and rough and abundantly folded in females. These structures greatly
      increased the absorptive surface of the worms. In conclusion, ivermectin is able
      to enter adult O. ochengi males at concentrations sufficient to kill non-filarial
      nematodes.

PMID- 9924551
TI  - Human gnathostomiasis caused by Gnathostoma doloresi, with particular reference
      to the parasitological investigation of the causative agent.
AB  - Gnathostomiasis caused by Gnathostoma doloresi Tubangui was observed in a 46-year
      old Japanese man, a clerk, who resided in the Fukuoka prefecture of Kyushu
      district, in southern Japan. The first symptom noted by the patient was
      epigastric pain, which occurred 3 days after he had consumed the raw flesh of a
      brook trout, Oncorhynchus masou masou (Brevoort), from a trout farm in
      neighbouring Kumamoto prefecture. Three days later, he developed creeping
      eruptions on his trunk. The eruptions spread and the patient was admitted to
      hospital 18 days after eating the trout. No nematode larvae were found in any of
      four skin biopsies collected on admission. However, vesicles appeared on the
      lower abdomen of the patient 20 days after he had eaten the trout, and a small
      nematode was removed from one of them. One day after the nematode had been
      excised, a cutaneous swelling suddenly occurred on the patient's lower left jowl
      and this persisted for a week. All the skin abnormalities gradually decreased
      from day 25 post-ingestion and had disappeared by day 30. The isolated nematode
      was identified as an advanced third-stage larva of G. doloresi, based on its
      morphology and the number of hooklets on its head-bulb.

PMID- 9924552
TI  - Anti-sporozoite immunity and impregnated bednets in Tanzanian villages.

PMID- 9924553
TI  - Serological response to Leishmania infantum in a patient treated with prednisone.

PMID- 9924554
TI  - Recognition and management of childhood cardiac arrhythmias.
AB  - Cardiac arrhythmias are common in children, but most of them are benign and do
      not signify underlying heart disease. However, the main tachyarrhythmias (SVT and
      VT) can cause cardiovascular collapse, and should therefore be treated promptly.
      Drug treatment is generally effective and is appropriate in stable patients. DC
      shock is the treatment of choice in patients with compromised circulation. There
      is a wide array of antiarrhythmic drugs and though they are generally safe, most
      of them have the potential for serious adverse effects. Hence, there is a need to
      exercise caution and balanced judgement in prescribing them. It is perhaps best
      for the general duty paediatric staff to be familiar with a select few, and stick
      to them if possible. Management of most cases of cardiac arrhythmia in children
      is within the competence of non-cardiologist paediatric staff. But in some
      instances cardiology referral will be required, either for further
      investigations, for decision regarding longterm drug therapy, or for more
      technical management modalities.

PMID- 9924555
TI  - The early natural history of vertically transmitted HIV-1 infection in African
      children from Durban, South Africa.
AB  - Forty-eight children with vertically transmitted HIV-1 infection and 93
      uninfected infants were followed up at regular intervals from birth for a mean of
      26 months. They were examined physically, growth and development were assessed
      and illnesses recorded. Seventy per cent of infected infants were symptomatic by
      6 months. Relative risks in the infected infants were highest for lymphadenopathy
      (4.56; CI 2.7-7.7), failure to thrive (4.48; 2.57-7.81), and neurological
      abnormalities (3.32; 1.9-5.58). The most frequent findings were diarrhoea (78%),
      pneumonia (76%) and lymphadenopathy (70%). Thrush and pneumonia occurred early
      but declined over time, whereas diarrhoea and neurological abnormalities occurred
      later and increased in frequency. A diagnosis of AIDS was made in 44% of infected
      infants by 12 months of age. Mortality in infected infants was 35.4%, and 76% of
      deaths occurred within the 1st year. About two-thirds of HIV-infected infants
      survived into early childhood. In South African children with vertically acquired
      HIV-1 infection the onset of disease is early and deterioration to AIDS and death
      are rapid. Infected infants can be easily recognized clinically, the majority by
      6 months of age.

PMID- 9924556
TI  - A prospective study of bacterial meningitis in children from north-eastern Libya.
AB  - During a 14-month period, 77 children (excluding neonates) with bacterial
      meningitis were studied. The causative organisms were identified in 60 children:
      Haemophilus influenzae in 26 (34%), Streptococcus pneumoniae in 20 (26%), Gram
      negative enteric bacilli in nine (12%) and beta-haemolytic streptococci group A
      in one. No organism was identified in 17 (22%) cases. The male to female ratio
      was 1.2:1. The age group most affected was between 2 and 12 months. The case
      mortality rate was 13% and nine children (12%) were left with permanent
      neurological sequelae.

PMID- 9924557
TI  - Shigellosis in children: a clinico-epidemiological comparison between Shigella
      dysenteriae type I and Shigella flexneri.
AB  - We reviewed the clinical and epidemiological features of 390 children under 5
      years of age infected with either Shigella dysenteriae type I or Shigella
      flexneri attending a diarrhoea treatment centre from 1993 to 1995 in Dhaka,
      Bangladesh. Older age (24 months or more), underweight and wasting but not
      stunting were the host factors significantly more associated with Shigella
      dysenteriae type I infection than in Shigella flexneri-infected children.
      Moreover, use of antibiotics at home, use of water from tubewells or pipe-water
      for drinking and lack of sanitary facilities for defaecation were the behavioural
      and environmental factors strongly associated with S. dysenteriae type I
      infection. Children with diarrhoea due to S. flexneri presented with more
      watery/liquid stools and had a shorter duration of illness. Duration of diarrhoea
      for 4 or more days was typical of S. dysenteriae type I infection. Interventions
      to address malnutrition and to promote environmental hygiene would be predicted
      to offer greater protection against shigellosis due to S. dysenteriae than S.
      flexneri.

PMID- 9924558
TI  - Infant feeding practices in Papua New Guinea.
AB  - Concern about a possibly increasing prevalence of bottle-feeding led in 1995 to
      an Infant Feeding Survey of 1822 mothers attending urban health facilities.
      Infant feeding practices including feeding of colostrum, exclusive breastfeeding,
      weaning practices and bottle-feeding were assessed. This revealed that 28.8% of
      mothers had not given colostrum to their babies, that 43.5% of 3-month-old babies
      were exclusively breastfed, and that solids were introduced before 4 months of
      age in over half of the study population. Bottle-feeding was used by 20% of the
      study population. Feeding practices differed in women of Highlands and of Coastal
      origin. The findings emphasize the need to strengthen health education programmes
      which take into account the mothers' different cultural backgrounds. The issue of
      breast-feeding by mothers in paid employment needs to be addressed.

PMID- 9924559
TI  - The effect of theophylline on apnoea and hypoxaemic episodes in the premature
      neonate during the 1st 3 days after birth.
AB  - Although the effect of theophylline on apnoea is well documented, its influence
      on hypoxaemic episodes in premature neonates is less well known. To investigate
      the influence of the drug on both parameters, 37 apnoeic neonates were monitored
      before and after theophylline treatment. Incidents and densities of pathological
      apnoea (cessation of nasal airflow > or = 20 seconds) were recorded. A fall of >
      or = 10% for > 10 seconds in peripheral oxygen saturation was classified as a
      hypoxaemic episode. Ethical constraints precluded the inclusion of a control
      group. Each infant served as its own control. Theophylline serum concentrations
      were 5.6 (3.4), 8 (7.1) and 8 (5.3) mg/l on days 1, 2 and 3, respectively. The
      apnoea incidents and densities decreased significantly (p = 0.0001) from baseline
      on all 3 days. The total number of hypoxaemic episodes, as well as those not
      associated with pathological apnoea, decreased, though not significantly.
      However, those hypoxaemic episodes associated with pathological apnoea and a fall
      in pulse rate of > or = 20% decreased significantly from baseline on day 2 only.
      Throughout the study period, over 80% of hypoxaemic episodes were not associated
      with apnoea. It is concluded that in the doses used, theophylline was more
      effective in reducing apnoea than hypoxaemic episodes in premature neonates.

PMID- 9924560
TI  - Awareness of environmental issues and the acceptance of CFC-free inhalers.
AB  - With the recent availability of a chlorofluorocarbon (CFC)-free metered dose
      inhaler (MDI) (Airomir), a patient survey was carried out to evaluate awareness
      of the role of CFCs in our environment and acceptance of this new inhaler. A
      questionnaire survey was conducted on parents and guardians of 201 children.
      Depending on respondents' preference, the interview was conducted in English
      (71%), Chinese (23%), Malay (5%) or Tamil (1%). A 'taste' test was also conducted
      on 103 of these children. Only 13% (26/201) of parents/guardians were aware that
      MDIs contained CFCs. Although 70% of children were in favour of the new taste of
      the CFC-free inhaler, the cost of the new inhaler was an important consideration
      for parents and guardians in their decision to switch to the new inhaler. The
      majority (93%) were willing to switch if its cost were equivalent to their
      current inhaler. This study has provided pertinent information with regard to
      acceptance of CFC-free inhalers which should be considered when making the
      inevitable switch to environmentally friendly inhalers.

PMID- 9924561
TI  - Causes of mortality in twins in a rural region of The Gambia, West Africa.
AB  - Little is known about birth or mortality rates of twins in The Gambia. There are
      no reports of the causes of death among twins in sub-Saharan Africa. We
      identified twin births and deaths from a community-based study which had been
      carried out in a large rural region of The Gambia over a 5-year period from 1989
      to 1993. The overall twinning rate excluding stillbirths was 14.3 (95% CI 12.9,
      15.8) per 1000 live deliveries. This was significantly lower among the Mandinka
      ethnic group (8.8 per 1000) than among the Serahulis (15.1 per 1000) or Fulas
      (18.3 per 1000). The early-neonatal, late-neonatal and post-neonatal twin
      mortality rates were 114.0, 45.9 and 64.2 per 1000 live twin births,
      respectively. In comparison, the early-neonatal, late-neonatal and post-neonatal
      mortality rates of singletons were 18.6, 16.0 and 41.1 per 1000, respectively. In
      the post-neonatal period, malnutrition was more frequently a cause of death among
      twins than among singletons (7.8 per 1000 twin births vs 2.0 per 1000 singleton
      births; p = 0.0008). Appropriate strategies for preventing malnutrition are
      required for this high-risk group.

PMID- 9924562
TI  - Spontaneous rupture of infantile umbilical hernia: report of three cases.
AB  - Three Nigerian infants with spontaneous rupture of an umbilical hernia are
      described. In two, hernias developed in the neonatal period following umbilical
      sepsis. Rupture occurred at the ages of 2 and 3 months, respectively, and was
      probably precipitated by raised intra-abdominal pressure resulting from excessive
      crying. The third child had a large, ulcerated umbilical hernia which ruptured at
      10 months and was precipitated by damage to the overlying skin. The children were
      treated successfully.

PMID- 9924563
TI  - Serum lipoprotein (a) concentrations among Arab children: a hospital-based study
      in Kuwait.
AB  - Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for premature
      atherosclerosis and coronary heart disease, both of which are prevalent among
      Kuwaitis. Our objective was to measure serum lipids, including Lp(a), in Arab
      children and compare them with values reported for other ethnic groups. To that
      end, serum concentrations of Lp(a), total cholesterol [T-CHOL], high density
      lipoprotein [HDL], low density lipoprotein [LDL], and triglyceride [TG] were
      assessed in 103 Arab children. The mean and median Lp(a) were 140.4 mg/l and 95
      mg/l, respectively. The Lp(a) frequency distribution was skewed to the right with
      the highest frequencies appearing at low levels. Serum Lp(a) correlated
      positively with T-CHOL and LDL but did not correlate with age, HDL and TG. Only
      nine children (8.7%) had serum Lp(a) levels associated with increased
      cardiovascular risk, namely > or = 300 mg/l.

PMID- 9924564
TI  - Two Afro-Trinidadian siblings with end-stage renal disease.
AB  - The case histories of two Afro-Trinidadian brothers aged 8 and 11 years who
      developed end-stage renal disease (ESRD) are presented. Neither had had cause in
      the past to seek medical attention for any renal-related illness. At presentation
      both had anaemia, growth failure and other clinical and laboratory evidence of
      ESRD. Kidney histology in one child was consistent with familial juvenile
      nephronophthisis (NPH). This is a common cause of ESRD in children in other
      countries but it has not been recognized previously in Trinidadian and other West
      Indian children, and should be considered as a possible aetiology in West Indian
      children presenting with renal failure.

PMID- 9924565
TI  - Gangrenous cholecystitis due to kala-azar.

PMID- 9924566
TI  - The efficacy of alternative spacer devices for delivery of aerosol therapy to
      children with asthma.
AB  - Spacer devices are important aids for use with metered dose inhalers in children
      with asthma. However, expense and unavailability of commercially produced spacers
      in developing countries have limited their use. Home-made spacers in the form of
      cups or bottles are widely used despite a lack of data confirming their efficacy.
      We investigated the relative efficacy of three spacers (a commercially available
      spacer, a modified 500-ml cold drink bottle and a polystyrene cup) for delivery
      of aerosolized drugs to asthmatic children older than 5 years. We also
      investigated the effect of leaks in the delivery system by comparing delivery via
      a sealed and an unsealed cold drink bottle. Lung deposition of aerosolized Tc-99m
      DTPA inhaled via spacer was measured in 30 patients. The median aerosol
      deposition in the lungs was significantly greater for the conventional spacer
      than for the cup (31.5% vs 9.5%; Z = -2.8, p = 0.005). Median aerosol deposition
      for the conventional spacer and sealed bottle were equivalent (40.5% vs 44%).
      Aerosol deposition from the sealed and unsealed bottle was significantly
      different (43.5% vs 24%; Z = -2.54, p = 0.01); however, the unsealed bottle was
      more efficient than the cup. We conclude that a modified 500-ml cold drink bottle
      is an efficient spacer. Leaks in this system are a major factor affecting the
      amount of drug deposited. The modified polystyrene cup is not an efficient
      spacer, delivering between a third and a fifth of the dose that other spacers
      were capable of delivering.

PMID- 9924567
TI  - Kangaroo care versus incubator care in the management of well preterm infants--a
      pilot study.
AB  - This pilot study was conducted to compare the effectiveness of the kangaroo care
      method with current, mainly incubator-based care in managing well preterm infants
      in a tertiary level hospital in a developing country. Altogether, 74 infants (37
      per group) were consecutively allocated to receive either kangaroo care or
      incubator care. After adjusting for age and weight on admission to the study, we
      found that infants in the kangaroo care group gained twice as much weight per day
      (20.8 vs 10.2 g, p = 0.0001), had a shorter stay in hospital (16.6 vs 20.7 days,
      p = 0.0457) and had a better survival rate (0% vs 9% deaths). Also, they were ill
      less frequently, but after adjusting for age and weight this difference was not
      significant. This pilot study suggests that the kangaroo care method has major
      advantages over incubator care of preterm infants in our hospital. Hospitals
      which cannot use incubators optimally may find kangaroo care to be a better
      method of improving perinatal and neonatal morbidity and mortality.

PMID- 9924568
TI  - Respiratory viruses in children attending a major referral centre in Saudi
      Arabia.
AB  - Viral respiratory infections are common causes of illness in infants and
      children. Examination of clinical specimens submitted for diagnosis during a 3
      year period (August 1993-July 1996) at King Faisal Specialist Hospital and
      Research Center (KFSH & RC) in Riyadh revealed a wide spectrum of diseases
      associated with the isolation of five respiratory viruses. Severity of disease
      ranged from mild upper respiratory illness to threatening lower respiratory
      illnesses including bronchiolitis and pneumonia. Of the 256 isolates, respiratory
      syncytial virus (RSV) accounted for 73 (28.5%), adenoviruses for 70 (27.3%),
      influenza viruses for 61 (23.8%), enteroviruses for 39 (15.2%) and para-influenza
      for 13 (2.3%). Viruses were found more frequently in children attending emergency
      or paediatric wards than in outpatients. RSV appears in November and the seasonal
      peak occurs during January and February. Influenza activity begins in September
      and peaks in November and December. Para-influenza type I emerges in winter and
      para-influenza type III follows the influenza epidemic and may be detected
      sporadically in summer. The other viruses (enteroviruses, adenoviruses) were
      isolated throughout the year.

PMID- 9924569
TI  - Epidemiology of clinical hyperbilirubinaemia in Al Ain, United Arab Emirates.
AB  - All infants born at Al Ain Hospital, United Arab Emirates between 1 January and
      30 June 1995 who developed clinically relevant hyperbilirubinaemia defined as
      jaundice requiring investigation and treatment were prospectively studied. Of the
      2300 live births, 85 (3.7%) developed hyperbilirubinaemia. Of these, 22 were
      premature, 22 had ABO haemolytic disease of the newborn, eight had G6PD
      deficiency (Mediterranean), seven had breast-milk jaundice, five were born to
      mothers with diabetes mellitus and one had Rh incompatibility. No specific factor
      was identified in 20 (24%). Significant differences in the distribution of
      diagnostic categories were found among the major ethnic groups in the population
      studied. This first study of the epidemiology of clinically relevant
      hyperbilirubinaemia in this community identified locally relevant risk factors
      and highlighted areas of health care which, if modified, might reduce the
      incidence of hyperbilirubinaemia.

PMID- 9924570
TI  - Epidemics of aseptic meningitis due to enteroviruses following national
      immunization days in Bahrain.
AB  - We report two successive epidemics of aseptic meningitis due to enteroviruses
      (EV) observed after national immunization days against polio. Meningitis due to
      echovirus 30 occurred from July 1995 to the end of January 1996, mostly among
      children aged 0-12 years (95.1% of cases), and meningitis due to echovirus 4
      occurred from May 1996 to the end of September 1996 in the same age group. There
      were 286 and 169 cases, respectively. Specimens from several representative cases
      were sent to the WHO Collaborating Center for Virus Reference and Research
      Laboratory for serological testing and virus detection, including polymerase
      chain reaction (PCR) studies. Using those tests, evidence of echovirus 30
      infection was found in 44% of the children who were sampled during the first
      epidemic and 45.5% during the second. During echovirus 30 and echovirus 4
      epidemics, a similar decline in the age-specific attack rate from 19.1/10,000 and
      10.1/10,000 population aged 12 years to 2.4/10,000 and 3.6/10,000 population aged
      13 years was observed, respectively.

PMID- 9924571
TI  - Characterization of VP6 subgroup, VP7 and VP4 genotype of rotavirus strains in
      Lusaka, Zambia.
AB  - In a previous study, rotavirus infection was determined in young children at the
      University Teaching Hospital in Lusaka. In this study, selected rotavirus strains
      were characterized by monoclonal antibody assay to the VP6 subgroup antigen
      present and by hybridization analysis of the VP7 and VP4 genes carried by the
      virus. The majority of the strains were characterized as a VP6 subgroup II, VP7
      serotype G1 strain with a long electropherotype and bearing the VP4 P8 genotype.
      A further four minor rotavirus strains with a long RNA electropherotype and
      subgroup II antigen were also observed to be circulating bearing G1 or G4 VP7
      genes and the VP4 P8 genotype. Two electrophoretic strains with differing short
      RNA electropherotypes and subgroup I antigenicity were also present. These
      strains hybridized to the VP7 type G2 and VP4 P4 genotype probes.

PMID- 9924572
TI  - Clinical predictors of outcome in hypoxic ischaemic encephalopathy in term
      neonates.
AB  - Thirty-eight full-term infants with hypoxic ischaemic encephalopathy were
      followed up prospectively to determine simple predictors of outcome at 1 year.
      Three predictors of outcome, based on clinical examination alone, were evaluated.
      These were presence of seizures, grading of encephalopathy and neurobehavioural
      assessment at discharge from the hospital. Development was assessed using the
      Bayley scales of infant development, and a mental and motor quotient below 85 was
      considered to be delayed development. At 1 year, 15 infants showed delayed
      development; five of them had cerebral palsy. Predictive values were determined
      for each indicator. Seizures per se did not affect the outcome. All infants with
      mild encephalopathy were normal. The predictive value of moderate-to-severe
      encephalopathy was 50%. Abnormal neurobehaviour at the age of 7 days or at
      discharge, if earlier, was found to be the best predictor of outcome with a
      predictive value of 91.6%.

PMID- 9924573
TI  - Chloramphenicol in children: dose, plasma levels and clinical effects.
AB  - Despite concerns about adverse effects, chloramphenicol (CMC) continues to be
      used in certain situations and, due to its low therapeutic index and variable
      pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our
      centre, CMC finds applications in typhoid and meningitis and TDM is routinely
      performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore
      decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in
      children, who constitute most of our patients. Our objective was also to develop
      strategies to improve our TDM for CMC use. Data were collected from 168 children
      given CMC for various indications and monitored by the TDM service. Plasma CMC
      was determined by HPLC and used to adjust doses to maintain concentrations within
      a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and
      haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged
      40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations
      were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days
      and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine
      children with other diagnoses died. Side-effects were confined to mild reversible
      haematological abnormalities which developed in 11% of children at plasma
      concentrations which tended to be high. We conclude that CMC remains useful in
      children with typhoid. Its use for other indications, however, should be
      reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer
      role is defined by well designed prospective studies.

PMID- 9924574
TI  - Clinical epidemiology of paediatric disease at Nchelenge, north-east Zambia.
AB  - In a combined retrospective and prospective 4-year study of 6412 children
      consecutively admitted to St Paul's Hospital, Nchelenge, north-east Zambia, the
      clinical epidemiology of paediatric disease was described. One diagnosis per
      admission was noted. Protein-energy malnutrition (PEM) was diagnosed clinically
      and by means of a modified Wellcome scheme using weight-for-height and Z scores.
      Correlation coefficients were calculated between monthly admission rates and
      relative humidity, rainfall and temperature. The age distribution of admitted
      children showed several distinct groups. Type I (malaria, acute gastro-enteritis,
      pneumonia and meningitis) had its peak in the 1st 7 months of age, type II (burn
      wounds and measles) had its main prevalence between the ages of 2 and 4 years,
      and type III (trauma, typhoid fever, snake bite and tropical ulcer) occurred
      mainly between 4 and 14 years of age. Admission rates for PEM, PEM subtypes,
      pneumonia, trauma and snake bite correlated with wet season variables. Malaria
      and acute gastro-enteritis were extremely common throughout the year. A measles
      epidemic in the dry season was initially followed by an increase in marasmus,
      whereas oedematous malnutrition only assumed epidemic proportions associated with
      a post-measles rise in admission rates of pneumonia. Clinical epidemiological
      data at the district level is a powerful tool for understanding the pattern of
      serious paediatric disease in the community.

PMID- 9924575
TI  - Paediatric enema syndrome in a rural African setting.
AB  - We have observed a distinct clinical syndrome amongst acutely unwell children
      frequently associated with the administration of a traditional medicine enema. We
      describe the clinicopathological features of this 'enema syndrome' based on
      retrospective case note review of 50 consecutive admissions to a South African
      rural district hospital. Admission was frequently prompted by sudden, marked
      clinical deterioration following enema administration (68% seen within 24 h).
      Respiratory distress with tachypnoea, abdominal distension, hypotonia and loss of
      consciousness occurred frequently. In-hospital mortality was 28% and was higher
      in those receiving herbal (43%) rather than chemical (21%) enemas. Hyperkalaemia,
      leucocytosis (> 15,000 mm3) and respiratory distress occurred more frequently in
      those who died. Diagnosis of an underlying illness was established in 78%. Whilst
      the majority of enemas are given without incident, children struggling with an
      underlying illness may be unable to tolerate rectally administered traditional
      medicines. Toxic chemical substances in frequent use may increase complication
      rates.

PMID- 9924576
TI  - The impact of short stature on child morbidity in a rural African community.
AB  - This study was undertaken to assess whether short stature in children under 5
      years of age is associated with an increased risk of acute or persistent
      diarrhoea, acute respiratory infection, or indeed any illness, taking account of
      possible confounding factors such as whether breastfed, water quality, degree of
      household crowding, age and gender. After initial anthropometric assessment, the
      morbidity and diet of a cohort of 403 Somali children were recorded for 1 year at
      2-week intervals. In multivariate analyses of the findings, adjustments were made
      for the possible confounding factors listed. Short stature was associated with an
      increased incidence of acute diarrhoea (< -2 SD score, RR 1.7, 95% CI 1.3-2.2)
      and with a risk of developing persistent diarrhoea, but not with the incidence of
      acute respiratory infections. When adjusting for age only, short stature
      increased the risk of developing any illness, but this association was not shown
      when adjusting for the other possible confounding factors. There was a dose
      effect relationship between different degrees of short stature and acute
      diarrhoea, with an increased incidence of acute diarrhoea among the shortest
      children. Efforts were made to account for the possibility of reverse causality,
      which seemed not to change the main findings. Thus, short stature seemed to
      increase the risk of subsequent acute diarrhoea in children under 5 years of age.

PMID- 9924577
TI  - Impact of a case management protocol for childhood pneumonia in a rural Zambian
      hospital.
AB  - This study aimed to assess the impact of adopting the WHO case management
      protocol for childhood pneumonia in a district hospital in rural Zambia. The
      subjects were children under 5 years of age with a diagnosis of pneumonia,
      admitted in the 9-month period following introduction of the WHO protocol.
      Management and outcome were compared with a historical control group admitted
      during the same period in the previous year. There were 158 children in the
      intervention group and 135 controls with similar age and sex distribution. Both
      groups were malnourished (mean weight-for-age Z score in subjects = -1.91, in
      controls = -1.83). There was no significant difference in the numbers receiving
      parenteral antibiotics or supplementary fluids in each group. However, children
      in the intervention group were significantly more likely to receive oxygen (odds
      ratio 4.7, 95% confidence interval 2.8-8.1, p < 0.0001). Mortality was
      significantly greater in the control group (case fatality rate, 25%) compared
      with the intervention group (case fatality rate, 15%; chi 2 = 4.6; p = 0.032).
      The introduction of the WHO protocol for management of childhood pneumonia and
      training of staff in its use was accompanied by a fall in mortality from this
      condition in a rural hospital. The improved survival rate may be related to the
      more frequent use of oxygen.

PMID- 9924578
TI  - Neonatal meningitis and septicaemia caused by Burkholderia pseudomallei.
AB  - We report a case of meningitis and one of fatal septicaemia in neonates due to
      Burkholderia pseudomallei and review the literature on neonatal melioidosis.
      Pneumonia was the primary presentation and was complicated by shock in the latter
      case. The epidemiological findings suggest that the cases reported from Malaysia
      were community-acquired in contrast with those from the USA and Thailand.

PMID- 9924579
TI  - Tuberculous meningitis and co-infection with HIV.
AB  - The clinical, laboratory and radiological features of 30 children with clinically
      diagnosed tuberculous meningitis (TBM) who were HIV-seronegative were compared
      with those of ten HIV-infected children with TBM. Such comparative data are not
      currently available in the literature and so are an important addition to our
      knowledge of the HIV-TB co-infection epidemic. In comparison with the HIV
      negative children, those infected with HIV were younger, had a shorter duration
      of symptoms and were more often Mantoux-negative (HIV-positive 23% vs HIV
      negative 70%; p = 0.01). On presentation, all children in both groups were in MRC
      TBM stages II or III. Clinical features were similar in both groups but computed
      tomography of the brain showed more ventricular enlargement (HIV-positive 80% vs
      HIV-negative 63%), gyral enhancement (HIV-positive 60% vs HIV-negative 17%; p =
      0.01) and cerebral atrophy (HIV-positive 40% vs HIV-negative 17%). Outcome was
      considerably worse in the HIV-positive children, of whom 30% died (vs HIV
      negative 0/30; p = 0.01) and the remainder were moderately (HIV-positive 30% vs
      HIV-negative 24%) or severely (HIV-positive 30% vs HIV-negative 19%) handicapped
      at the end of treatment. While clinical features were not markedly different in
      HIV-infected and uninfected children with TBM, abnormal radiological findings
      were more common in the HIV-infected group and outcome was considerably worse. Co
      existing HIV encephalopathy and diminished immune competence undoubtedly
      contributed to the more severe clinical and neuro-radiological features.

PMID- 9924580
TI  - Electroencephalographic photosensitivity among Zimbabwean youths.
AB  - To clarify the factors associated with electroencephalographic (EEG)
      photosensitivity, the records of patients who had EEG examinations in the city of
      Harare, Zimbabwe between 1968 and 1996 were studied. EEG photosensitivity was
      confirmed in 107 of a total of 9082 youths (aged 0-25 years), giving an overall
      photosensitivity prevalence of 1.17% in the study population. Photosensitivity
      occurred more frequently in females than in males, and the peak age period for
      its occurrence was during adolescence. A significantly higher prevalence of
      photosensitivity was recorded among Whites and Asians than among Blacks, while
      the Coloured population had an intermediate prevalence. The monthly and seasonal
      incidence of photosensitivity in the present study showed no correlation with the
      prevailing mean monthly or seasonal temperatures, sunshine duration and sunlight
      intensity in Harare during the period covered by the study. These findings
      indicate that sunshine-related factors do not play a dominant role in the
      occurrence of photosensitivity, thereby negating previous opinions which
      attributed the relative rarity of photosensitivity in black Africans to high
      levels of exposure to sunshine in tropical Africa. Our findings therefore
      corroborate the view that photosensitivity depends primarily on genetic rather
      than environmental factors.

PMID- 9924581
TI  - Bacteraemia in cerebral malaria.
AB  - As part of a treatment trial of cerebral malaria, blood cultures were done in 276
      Gambian children, aged between 1 and 9 years, with cerebral malaria. Fourteen
      (5%) of these were positive. The organisms isolated were Staphylococcus aureus
      (6), coliforms (4), Pseudomonas spp. (2), Salmonella spp. (1) and Streptococcus
      spp. (1). Thirteen of these children survived, most without appropriate
      antibiotic treatment. Most of the retrieved organisms were therefore suspected to
      be contaminants. Bacteraemia complicating cerebral malaria is not common in The
      Gambia, and routine antibiotic treatment of children with cerebral malaria is not
      warranted.

PMID- 9924582
TI  - Neonatal meningitis in Addis Ababa: a 10-year review.
AB  - In a hospital population-based retrospective study of neonatal meningitis, 55
      cases were identified over a period of 10 years. The prevalences of meningitis
      for preterm and term newborns were 3.66 and 0.97 per 1000, respectively (22/6465
      vs 33/36638; p < 0.01). The overall prevalence was 1.37 per 1000 live births.
      Twenty-two (40%) babies with meningitis died, more preterm than term (13/22 vs
      9/33; p < 0.05). Known maternal risk factors for neonatal meningitis were
      observed in 15 (27%) babies. The risk factors were more common in preterm than in
      term newborns (10/22 vs 5/33; p < 0.05). The common causative organisms were
      Klebsiella pneumoniae, Escherichia coli and Enterobacter spp. which together
      accounted for 67% of all CSF isolates. These organisms were evenly distributed
      between early- and late-onset meningitis, and among term and preterm newborns.
      Seven of 33 (21%) of the surviving newborns developed neurological complications.
      The short-term sequelae were hydrocephalus, spastic paresis and seizures.

PMID- 9924583
TI  - Screening for congenital hypothyroidism in cognitively delayed children.
AB  - During the period January 1994 to December 1997, a total of 560 cognitively
      delayed children were prospectively screened for congenital hypothyroidism in the
      paediatric neurology clinic at Jordan University Hospital. Seventeen (3%)
      children were diagnosed to have congenital hypothyroidism. Mean age at diagnosis
      was 15 months (range 1.8-72 months). Main presenting symptoms (other than
      cognitive delay) were seizures, lethargy, poor feeding, constipation and
      prolonged neonatal jaundice. Thirteen (76.5%) of the 17 extrathyroid-associated
      anomalies involved the central nervous system (CNS). This finding reflects the
      study population chosen for the present study. All 17 patients had some degree of
      cognitive improvement ranging from slight improvement to achieving normal
      milestones after taking L-thyroxine. Congenital hypothyroidism is common in
      cognitively delayed children. The presence of major abnormality of the CNS should
      not be regarded as the only possible cause of cognitive delay and thyroid
      function should be assessed in such children.

PMID- 9924584
TI  - An epidemic of dengue haemorrhagic fever/dengue shock syndrome in tropical India.
AB  - An epidemic of dengue haemorrhagic fever/dengue shock syndrome occurred in
      Chennai, South India in 1989 during and following the rainy season. Sixty-nine
      infants and children admitted to the Institute of Child Health and Hospital for
      Children with a brief febrile illness associated with skin and mucous membrane
      bleeds and/or shock were studied. Forty-nine had antibodies to dengue viruses.
      The specific serotype of the virus responsible could not be identified owing to
      cross-reacting antibodies. Primary infection occurred in 11 cases, secondary
      infection in 17 cases, antibodily titres were indicative of 'probable' dengue
      infection in 16 and were uninterpretable in five. In 11 cases, serology could not
      be done. The pattern of disease in these 60 cases was similar, with a high
      mortality. Haemoconcentration was not a feature in the majority and the Hess test
      was negative in all those tested. Nine cases with a similar but milder illness
      tested negative for dengue.

PMID- 9924585
TI  - Kawasaki disease in a paediatric hospital in Riyadh.
AB  - This is an analysis of the records of 29 children with Kawasaki disease (KD)
      admitted to Sulaimania Children's Hospital (SCH) in Riyadh in the period between
      January 1989 and December 1996. The aim was to review our experience with KD in
      Riyadh and the ability of our paediatricians to recognize the disease. The number
      of cases admitted from 1993 to 1996 (23) was significantly higher than the number
      of cases (six) admitted from 1989 to 1892. Of the 29 children who finally met the
      diagnosis of Kawasaki disease, 19 (66%) were diagnosed on admission.

PMID- 9924586
TI  - Parenting stress among mothers of Malaysian children with cerebral palsy:
      predictors of child- and parent-related stress.
AB  - A hospital study was carried out to compare parenting stress among 87 Malaysian
      mothers of children with cerebral palsy and a control group (comprising 87
      mothers of children without disability who attended the walk-in paediatric
      clinic), using the Parenting Stress Index (PSI) questionnaire. Multiple
      regression analysis was used to determine socio-demographic and medical factors
      associated with child-domain stress (CDS) and parent-domain stress (PDS). Mothers
      of children with cerebral palsy scored significantly higher than control subjects
      on all sub-scales of CDS and PDS (p < 0.01), except for the sub-scale of 'role
      restriction'. The presence of cerebral palsy (p < 0.001) and activities of daily
      living (ADL) scores (p < 0.001) were significantly associated with CDS. Factors
      predictive of PDS were ADL scores (p < 0.001), number of hospitalizations over
      the past year (p = 0.024), level of maternal education (p = 0.018) and Chinese
      mothers (p < 0.001). Although this study demonstrated that Malaysian mothers of
      children with cerebral palsy experienced higher levels of stress than controls,
      the impact of cerebral palsy per se on parenting stress was modified by other
      factors such as increased care-giving demands, low maternal education and ethnic
      background. Habilitation should be directed at easing the burden of daily care,
      minimizing hospital re-admissions and targeting appropriate psychosocial support
      at specific subgroups to change parental perception and expectations.

PMID- 9924587
TI  - Prediction of illness severity and outcome of children symptomatic following
      kerosene ingestion.
AB  - Kerosene pneumonitis is usually self-limiting and secondary infection is rare.
      Long-term studies in developed countries have produced conflicting results about
      complications. The position in developing countries, where children are exposed
      to adverse environmental and nutritional factors, is unknown. The aim of the
      present work was to determine whether there is an increase in respiratory or
      other illnesses following kerosene pneumonitis and whether these changes could be
      related to the severity of the initial lung damage. Fifty-seven children with
      clinical signs of pneumonitis were examined on admission and after overnight
      observation. Clinical signs were assessed for their usefulness for predicting
      severity. Cases and matched neighbourhood controls were seen every 2 weeks for 3
      months. The time to predict most reliably the severity of short-term ill effects
      was 12-24 hours after the initial insult. There was no significant difference in
      respiratory symptoms during the 3-month follow-up in cases compared with
      controls. However, mild diarrhoea and fever were reported significantly more
      often in cases than in controls. Morbidity after clinical recovery was not shown
      to be a problem, irrespective of the severity of the acute event.

PMID- 9924588
TI  - Astrovirus infection in South Africa: a pilot study.
AB  - Astroviruses have been shown to be important aetiological agents associated with
      gastroenteritis in children, as have rotaviruses and the enteric adenoviruses.
      However, no inclusive studies have been conducted in South Africa to allow a
      comparison of the relative roles of these different viral agents. In this study,
      stool specimens were obtained between 1991 and 1993 from 225 young children with
      acute gastro-enteritis. These were examined for the presence of astroviruses
      using a monoclonal antibody-based ELISA, and for rotaviruses and enteric
      adenoviruses using commercially available kits. A control group of 56 infants and
      young children without symptoms of diarrhoeal illness was included in the study.
      Astroviruses were detected in 7% of the stools compared with 20% infected with
      rotaviruses and only 3% infected with enteric adenoviruses. In the control group,
      one specimen each had astrovirus or adenovirus and two shed rotaviruses. The
      astrovirus prevalence observed in this study is similar to that reported in other
      developing communities. Rotavirus and astrovirus infections were more prevalent
      in the autumn and early winter than in other seasons. Astrovirus and rotavirus
      infections predominated in children between 3 and 22 months of age.

PMID- 9924589
TI  - Is zero dose oral polio vaccine effective in preterm babies?
AB  - A randomized controlled trial was done to compare seroconversion following a
      single dose of trivalent oral polio vaccine (TOPV) in preterm babies, vaccinated
      at two different post-conception ages, with that of term newborns. Sixty-two
      consecutive preterm babies < or = 35 weeks were randomly allocated to two groups.
      Group A was vaccinated 'early' at 34-35 weeks and group B 'late' at 38-40 weeks
      post conception. The two groups were comparable in birthweight [mean (SD) 1594 g
      (118) and 1599 g (126), respectively] and gestational age [mean (SD) 33.2 (1.2)
      and 33 (1.3) weeks, respectively]. A control group of 36 term babies (group C)
      were vaccinated in the 1st week of life. Polio virus antibodies were measured
      immediately before and 6-8 weeks after vaccination. Group A had seroconversion
      rates of 54.2, 12.5 and 12.5% against polio virus types 1, 2 and 3, respectively,
      group B had rates of 60.0, 8.0 and 16.0%, and group C rates of 53.6, 10.7 and
      14.3%. Differences in the seroconversion rates in the three groups were not
      statistically significant. The conversion rates against types 2 and 3 are much
      lower than in previous studies. We conclude that preterm babies vaccinated at 34
      35 weeks post conception show seroconversion rates similar to those in term
      newborns.

PMID- 9924590
TI  - Transcutaneous measurement of hyperbilirubinaemia: comparison of the Minolta
      jaundice meter and the Ingram icterometer.
AB  - The effectiveness of two different non-invasive transcutaneous bilirubin
      measurement devices was compared with serum bilirubin levels in 96 healthy
      newborns. Transcutaneous measurements were obtained with the Minolta Air Shields
      jaundice meter and the Ingram icterometer and serum bilirubin levels were
      determined by a direct spectrophotometric method (Bilitron 444). A linear
      correlation existed between serum bilirubin values and the readings on both the
      Minolta jaundice meter (r = 0.83) and the Ingram icterometer (r = 0.78). The
      Kappa coefficient was 0.66. the sensitivity, specificity and positive and
      negative predictive values were 100%, 56%, 33% and 100% for the Minolta jaundice
      meter and 100%, 48%, 29% and 100% for the Ingram icterometer, respectively. The
      high sensitivity and negative predictive value of both devices render them
      suitable for screening neonatal hyperbilirubinaemia. However, because of its low
      cost, the Ingram icterometer is preferable to the more complex and expensive
      Minolta jaundice meter, especially in countries with a high birth rate, such as
      Turkey.

PMID- 9924591
TI  - Respiratory rates of Indian infants under 2 months of age.
AB  - There are few data from developing countries, including India, on the normal
      range of the respiratory rate (RR) recorded by observation. To determine the
      normal range of RR in infants up to 8 weeks of age and to define tachypnoea, we
      studied 100 healthy infants, 50 of normal birthweight and 50 of low birthweight)
      at 1, 2, 4, 6 and 8 weeks of age. The RR was recorded by observation and
      auscultation simultaneously for 60 seconds on each visit when the baby was either
      asleep or awake and content. The median RRs ranged between 42 and 43 breaths/min
      in infants of normal birthweight and 40 and 44 breaths/min. in low birthweight
      infants. Inter-age variability up to 8 weeks of age was very slight and
      statistically insignificant. Only 2-10% of the infants at any given age had a RR
      > or = 60/min. At all ages, RR by observation was higher than that by
      auscultation (p < 0.001). Neither birthweight nor gender significantly influenced
      the RR. When awake, infants had significantly higher RRs than when asleep. The RR
      extrapolated from a 15-second breath count was significantly lower (p < 0.05
      0.01), whereas results from 30-second counts were similar to 60-second counts.
      Our data endorse the use of a RR > or = 60 breaths/min. counted for 1 minute as a
      cut-off to define tachypnoea in infants < 2 months of age.

PMID- 9924592
TI  - Salmonella enteritidis meningitis in a healthy neonate.

PMID- 9924593
TI  - Reducing temperature in febrile children.

PMID- 9924594
TI  - Cost effectiveness in palliative care.

PMID- 9924595
TI  - Do specialist palliative care teams improve outcomes for cancer patients? A
      systematic literature review.
AB  - The objective of the study was to determine whether teams providing specialist
      palliative care improve the health outcomes of patients with advanced cancer and
      their families or carers when compared to conventional services. The study
      involved a systematic literature review of published research. The source of the
      data included studies identified from a systematic search of computerized
      databases (Medline, psychINFO, CINAHL and BIDS to the end of 1996), hand
      searching specialist palliative care journals, and studying bibliographies and
      reference lists. The inclusion criteria for articles were that the study
      considered the use of specialist palliative care teams caring for patients with
      advanced cancer. Articles were assessed and data extracted and synthesized, with
      studies graded according to design. A variety of outcomes were considered by the
      authors. These addressed aspects of symptom control, patient and family or carer
      satisfaction, health care utilization and cost, place of death, psychosocial
      indices and quality of life. Overall, 18 relevant studies were identified,
      including five randomized controlled trials. Improved outcomes were seen in the
      amount of time spent at home by patients, satisfaction by both patients and their
      carers, symptom control, a reduction in the number of inpatient hospital days, a
      reduction in overall cost, and the patients' likelihood of dying where they
      wished to for those receiving specialist care from a multiprofessional palliative
      care team. It was concluded that all evaluations were of services considered to
      be leading the field, or were pioneering training and treatments. However, when
      compared to conventional care, there is evidence that specialist teams in
      palliative care improve satisfaction and identify and deal with more patient and
      family needs. Moreover, multiprofessional approaches to palliative care reduce
      the overall cost of care by reducing the amount of time patients spend in acute
      hospital settings.

PMID- 9924596
TI  - Relationships between symptom relief, quality of life, and satisfaction with
      hospice care.
AB  - Hospices were founded to alleviate suffering at the end of life. Quality
      improvement in hospices should, therefore, target patients' subjective
      assessments of their care and its outcomes. However, little is known about the
      relationships among subjective measures of care among hospice patients. The aim
      was to assess the relationships between hospice patients' physical and
      psychological symptoms, quality of life, and satisfaction with inpatient care.
      This was achieved with a prospective cohort study of 42 patients admitted to an
      Australian hospice's inpatient service during a two-month study period. The
      Edmonton symptom assessment system, McGill quality of life questionnaire, and a
      new measure of patients satisfaction with hospice inpatient care were used. It
      was shown that while there were marked variations in symptoms and quality of life
      scores, most patients were satisfied with their care. Satisfaction on the day
      after admission was lower among patients with worse quality of life scores (r = 
      0.40, P = 0.008), but there was no correlation with symptoms (r = -0.12, P =
      0.43). Among the 26 patients (62%) with at least one subsequent inpatient
      interview, satisfaction was correlated with both worse quality of life (r = 
      0.51, P = 0.01) and symptoms (r = -0.41, P = 0.05). The symptom, quality of life,
      and satisfaction scales all had sufficient precision to identify patients with
      significant changes between the two interviews. It can be concluded that
      satisfaction with hospice care was associated with quality of life more than
      symptoms, although symptoms became important later during inpatient stays.
      Patients can assess their care and can provide valuable information for improving
      palliative care.

PMID- 9924597
TI  - Do hospital palliative care teams improve symptom control? Use of a modified STAS
      as an evaluation tool.
AB  - The support team assessment schedule (STAS) has previously been validated as an
      evaluation tool for community palliative care teams and inpatient units. This
      study reports on use of an expanded STAS (E-STAS) to determine symptom prevalence
      and outcome for inpatients and outpatients referred to a multiprofessional
      hospital palliative care team. E-STAS forms were completed on patients at
      referral and twice weekly thereafter. Between August 1996 and May 1997, 352
      patients had one or more E-STAS forms completed; 122 of this group had three or
      more assessments. One-hundred-and-eighty-two patients were male and 170 were
      female, the median age was 68.5 years (range 26-101 years) and all but 27 (8%)
      had malignant disease. Of the symptoms assessed on referral, the most common were
      psychological distress 93%, anorexia 73%, pain 59%, mouth discomfort 59%,
      depression 40%, constipation 36%, breathlessness 32%, nausea 24% and vomiting
      13%. In the 122 patients where three or more assessment were completed,
      statistically significant improvements from first to last assessment were seen in
      all symptoms except depression. This study suggests that E-STAS may be a useful
      tool to evaluate interventions by a hospital palliative care team in patients
      with advanced disease.

PMID- 9924598
TI  - Where do cancer patients die? Ten-year trends in the place of death of cancer
      patients in England.
AB  - Although studies have found that 50-70% of cancer patients would prefer to die at
      home, there has been a trend towards the hospitalization of the dying in many
      countries. No study has attempted to analyse the changes in place of death in
      detail. The aim was to analyse the 10-year trends in place of death of cancer
      patients, by region and by diagnosis, within England. To do this, data on the
      place of death and patients' characteristics were derived from death
      registrations for all cancer deaths between the years 1985-94. We examined trends
      in the place of death for the whole of England, for each region separately and
      for the main cancer diagnoses. The results show that there were over 1.3 million
      death registrations from cancer during the 10 years. The mean age increased over
      the period from 69.9 years in 1985, to 71.3 years in 1994. The percentage who
      died in a UK National Health Service (NHS) hospital or nursing home fell
      gradually from 58% (1985) to 47.3% (1994), while the percentage who died in non
      NHS hospitals, nursing homes, hospices and communal establishments increased. The
      percentage who died at home fell slightly but steadily between 1985 and 1992 from
      27% to 25.5% and since then increased slightly to 26.5% in 1994. The percentage
      of home deaths was lowest in the two Thames regions (less than 25%) and highest
      in the West Midlands, Anglia and Oxford (over 29%). These differentials were
      maintained across age groups and diagnoses. Older people and women were less
      likely to die at home than younger people and men. Significant trends showing an
      increase in home deaths were found in two regions: North Thames and South Thames.
      Patients with cancers of the lung, colorectum, respiratory organs, bone or
      connective tissue and lip, oral cavity and pharynx were more likely to die at
      home (over 29% in 1994) than patients with cancers of the (breast (women, 25% in
      1994) or the lymphatic or haematological system 16% in 1994). It can be concluded
      that the trend towards a reducing home death rate from cancer in England appears
      to have halted, although this varies between regions. This has implications for
      primary care services. Although hospital is still the most common place of death
      from cancer, the percentage of cancer patients who die in hospital is reducing.
      The largest rise is in the increasing use of hospices and communal
      establishments, including residential and nursing homes. Given the ageing
      population, this trend is likely to continue.

PMID- 9924599
TI  - The attitude of health care professionals toward the availability of hospice
      services for cancer patients and their carers in Saudi Arabia.
AB  - The main objectives of this study were to assess cancer care and the need for
      establishing hospice/palliative care for cancer patients and their carers in
      Saudi Arabia. Six-hundred-and-ninety-five participants (136 cancer patients, 161
      informal carers, and 398 health care professionals) were recruited from oncology
      centres in four major regions of Saudi Arabia. Each group was asked to complete a
      questionnaire specifically designed to meet the aims of the study. The data
      obtained from the three different questionnaires indicated that the level of
      cancer care in the Ministry of Health hospitals was poor compared to other
      hospitals such as the King Faisal Specialist Hospital and Research Centre,
      military hospitals or university hospitals in the kingdom, perhaps due to the
      absence of home care services or periodic follow-up by their regional hospitals.
      It was also reported that the shortage of drugs used in cancer management, the
      severe restriction of prescribing narcotic analgesics and lack of cancer care
      knowledge were the major impediments to providing good cancer care. Thus, the
      strong inter-relationship among Saudi families, the present poor status of cancer
      care, cancer patients' and their carers' acceptability of hospice services and of
      the willingness of health care professionals to receive training in palliative
      care, illustrate the need for initiating the provision of palliative care
      services in the Saudi health system.

PMID- 9924600
TI  - The relationship between opioid use and laxative use in terminally ill cancer
      patients.
AB  - The frequency of the use of laxatives, and the relationship between doses of
      laxatives and of opioid analgesia, were determined by a prospective study of 498
      hospice inpatients with advanced cancer. Laxatives were required by 87% of
      patients taking oral strong opioids, 74% of those on weak opioids and 64% of
      those not receiving opioid analgesia. The form of the relationship appears to be
      hyperbolic, as suggested by the presentation of the results arranged by opioid
      quartile and by the improved correlation obtained by subjecting the opioid data
      to a logarithmic transformation. It is concluded that opioids account for about a
      quarter of the constipation found in terminally ill cancer patients in a hospice.
      However, the dose of laxative required is likely to be significantly higher if an
      opioid is being taken than if not. The form of the relationship between laxative
      and strong opioid doses is what might be expected from the mediation of opioid
      induced constipation by opioid receptors.

PMID- 9924601
TI  - Health professionals' responses to multiple sclerosis and motor neurone disease.
AB  - This study compares the responses of health professionals to multiple sclerosis
      (MS) and motor neurone disease (MND) in order to determine similarities and
      variations in responses to the two disorders and the issues critical to caring
      for patients with these conditions. Health professionals were more negative about
      MND compared with MS in terms of the amount they felt able to offer patients,
      their confidence in managing patients and their ability to convey hope. For a
      number of issues concerning the management of patients, the level of difficulty
      experienced by health professionals was similar for both MS and MND. These were
      resource issues, the health professionals' ability to remain positive in the face
      of progressive disability, interdisciplinary team problems and difficulties
      regarding patient care. The main concern of health professionals, for both
      conditions, was the effect of progressive disability on the patient. For MND,
      management issues which health professionals found comparatively more difficult
      than for MS were patients' short prognosis and impending death, communication
      problems and progressive disability. Issues which were comparatively more
      difficult for MS than MND were changes in patients' affect, cognition and
      personality, problems with planning care because of the disorder's unpredictable
      course, problems with diagnosis such as making and disclosing the diagnosis, and
      the tendency for patients to be difficult or demanding. Some notable differences
      in responses between health professionals in different health care settings were
      found. The findings have implications for changing health professionals'
      conceptualization of 'hope', developing ways of improving communication between
      health professionals in different health care settings so as to enable them to
      learn from each other's expertise and experiences and redressing gaps in service
      provision, especially for young people with MS.

PMID- 9924602
TI  - The drawback of the Hospital Anxiety and Depression Scale in the assessment of
      depression in hospice inpatients.

PMID- 9924603
TI  - Use of an unstructured patient-held record in palliative care.

PMID- 9924604
TI  - Developing a research culture for palliative care.

PMID- 9924605
TI  - Comprehensive mutational analysis of the TSC1 gene: observations on frequency of
      mutation, associated features, and nonpenetrance.
AB  - We performed a comprehensive analysis for mutations in the TSC1 gene using
      Southern blot analysis, and SSCP and heteroduplex analysis of amplified exons in
      13 families with genetic linkage to the TSC1 region, 22 small families without
      linkage information, and 126 sporadic patients. 17 unique mutations were
      identified in 21 patients. Mutations were found in 7/13 (54%) TSC1-linked
      families, 1/22 (5%) small families without linkage, and 13 of 126 (10%) sporadic
      cases. The mutations were all chain-terminating, with 14 small deletions, 1 small
      insertion, and 6 nonsense mutations. In families with mutations, all individuals
      carrying a mutation met formal diagnostic criteria for TSC, apart from a 3-year
      old girl who had inherited a deletion mutation, and who had no seizures, normal
      intelligence, normal abdominal ultrasound, and hypomelanotic macules only on
      physical exam. We assessed the incidence and severity of mental retardation in
      the 13 sporadic patients with TSC1 mutations versus the entire sporadic cohort,
      and found no significant difference. The observations indicate that TSC1
      mutations are all inactivating, suggest that TSC1 disease occurs in only 15-20%
      of the sporadic TSC population, and demonstrate that presymptomatic TSC does
      occur.

PMID- 9924606
TI  - A PDZ domain-containing protein with homology to Diphor-1 maps to human
      chromosome 1q21.
AB  - The novel gene, Diphor-1, was recently cloned from rat kidney and shown to
      increase phosphate uptake in cells when co-expressed with a Na(+)-Pi
      cotransporter, indicating that it may play a substantial role in cellular
      phosphate balance. Previously, the phosphate wasting disorder, autosomal dominant
      hypophosphatemic rickets (ADHR) was mapped to chromosome 12p13 by linkage
      analysis. In the present work, PDZK1, a PDZ domain-containing protein highly
      homologous to rat Diphor-1, was shown to be expressed in human kidney. Based upon
      its sequence similarity to rat Diphor-1, we considered PDZK1 a feasible candidate
      gene for ADHR. PDZK1 was found to localize to human chromosome 1q21, thereby
      ruling it out as a candidate for ADHR.

PMID- 9924607
TI  - Analysis of Australian Crohn's disease pedigrees refines the localization for
      susceptibility to inflammatory bowel disease on chromosome 16.
AB  - A number of localizations for the putative susceptibility gene(s) have been
      identified for both Crohn's disease and ulcerative colitis. In a genome wide
      scan, Hugot et al. (1996) identified a region on chromosome 16 which appeared to
      be responsible for the inheritance of inflammatory bowel disease in a small
      proportion of families. Subsequent work has suggested that this localization is
      important for susceptibility to Crohn's disease rather than ulcerative colitis
      (Ohmen et al. 1996; Parkes et al. 1996). We investigated the contribution of this
      localization to the inheritance of inflammatory bowel disease in 54 multiplex
      Australian families, and confirmed its importance in a significant proportion of
      Crohn's disease families; we further refined the localization to a region near to
      D16S409, obtaining a maximum LOD score of 6.3 between D16S409 and D16S753.

PMID- 9924608
TI  - Structure and organization of the human deoxyribonuclease II (DNase II) gene.
AB  - The structure of the human gene for deoxyribonuclease II (DNase II; EC 3.1.22.1)
      was determined using several specific primers based on the human DNase II cDNA
      sequence [Yasuda et al. (1998). J. Biol. Chem. 273, 2610-2616] in a polymerase
      chain reaction-based strategy. The gene spanned about 6 kb and consisted of 6
      exons. No canonical TATA or CAAT boxes could be identified within the 1341
      nucleotides upstream of the putative transcription start site, although the 5'
      flanking region contained a CpG island and several putative binding motifs for
      transcription factors Sp1 and ETF. These properties indicate that the DNase II
      gene is a housekeeping gene and this is compatible with its ubiquitous expression
      in human tissues. Three different cleavage/polyadenylation sites were identified
      in the 3'-flanking region, leading to the production of multiple DNase II mRNA
      species. However, a comparison of the entire translated sequences of the gene
      from a pair of subjects with homozygous DNase II phenotypes H and L revealed no
      differences in the nucleotide sequences.

PMID- 9924609
TI  - Major gene control of human body height, weight and BMI in five ethnically
      different populations.
AB  - Pedigree samples were collected from five ethnically and geographically different
      populations: Kirghizians, Turkmenians, Chuvashians, Israelis and Mexicans. All
      studied individuals were assessed for body height, weight and BMI. The sample
      size in the studied pedigrees ranged from 381 to 1811 individuals. Segregation
      analysis of these traits preliminarily adjusted for sex and age was performed by
      means of program package MAN that provides parameter estimates for the major gene
      effects, for the residual within the genotype correlations between relatives and
      for the assortative mating. By the usual transmission probability tests, the
      'environmental' model was strongly rejected for all measured traits in all 5
      populations. The major gene mode of inheritance, however, was accepted for all
      traits. The results of analysis in 5 populations were remarkably similar, and
      showed that except for Mexican sample, the proportion of variance attributable to
      major gene effect ranged between 37 and 53% for body weight and height. In the
      Mexican sample it explained only about 14% of the body weight variation. The
      proportion of inter-individual variation in BMI attributable to major gene effect
      was consistently lower in all populations in comparison with height and weight
      and ranged between 17 and 40%. Strong assortative mating in body height, as
      estimated by correlation between putative major gene genotypes in spouses, was
      found in four populations, not including Mexican pedigrees.

PMID- 9924610
TI  - Semiparametric linkage analysis using pseudolikelihoods on neighbouring sets.
AB  - For many complex diseases, study has suggested that the disease genes influence
      not only the occurrence of the disease, but also the age of onset. Current
      methods in linkage analysis are mainly concentrated on affected relative pairs or
      affected family members, and age of onset information is either ignored or is
      taken into account by specifying age-dependent penetrances for liability classes.
      In fact, affected relatives with different ages of onset may be the result of
      different genetic aetiologies and unaffected relatives are censored at the study
      time. Therefore, incorporation of age of onset and including contrasts between
      affected and unaffected pedigree members are important components of effective
      analysis for the detection of linkage with genetic markers. We use multiple
      markers to infer the inheritance vector in order to extract information about the
      inheritance pattern of the disease allele in a pedigree. For a given inheritance
      vector, we define two neighbour sets for each individual based on allele
      identical by descent (IBD). We then use the within-set and between-sets
      conditional hazard ratios to characterize the dependence of age of onset among
      relatives. A pseudolikelihood ratio test is proposed for testing linkage.
      Simulated and real data sets are used to illustrate these new statistical
      methods.

PMID- 9924611
TI  - A branching non-linear autoregressive model for the transmission of the fragile X
      dynamic repeat mutation.
AB  - A non-linear time series version of a model for the transmission of fragile X
      previously described in Ashley & Sherman (1995) is developed. The model retains
      the biological features of the Ashley/Sherman model but is easier to generalize
      and in particular allows the inclusion of covariates such as haplotype to model
      different paths and random effects to model family effects. The model is fitted
      to data from Murray et al. (1997) and its properties are illustrated in a
      simulation study.

PMID- 9924612
TI  - Statistically robust approaches for sib-pair linkage analysis.
AB  - Many traits that distinguish one individual from another, such as height or
      weight, are clearly heritable and yet vary continuously in populations.
      Continuous, heritable variation in trait levels presumably reflects the
      segregation of multiple genes, but elucidation of the genetic architecture of
      quantitative traits has been limited. Haseman & Elston (1972) developed a
      genetically robust method (HE) for detecting linkage to quantitative trait loci
      using sib-pairs. The method is based on a simple linear regression of the squared
      sib-pairs trait difference on the proportion of alleles shared identical by
      descent at a marker locus. Linkage is detected by a negative slope which has been
      traditionally assessed by a standard t-test. Wan, Cohen & Guerra (1997) have
      shown that the standard t-test is robust to the violations of the stochastic
      assumptions underlying the test. In practice, however, the standard t-test, based
      on least-squares regression, is sensitive to outliers. The presence of outliers
      in the data can lead to false positive and false negative linkage results.
      Accordingly we have developed and evaluated a statistically robust procedure for
      the HE approach to linkage. The procedure is based on robust regression.
      Simulation studies show that this robust procedure has greater power than the
      standard t-test in the presence of outliers, and has similar power to the
      standard t-test in the absence of outliers. This robust procedure also shows
      greater power than rank-based approaches either in the absence or presence of
      outliers. To illustrate the methods using real data we reanalyse data from two
      lipoprotein systems that motivated this work.

PMID- 9924613
TI  - Learning from Henry Spira.

PMID- 9924614
TI  - Henry Spira's search for common ground on animal testing.

PMID- 9924615
TI  - The ethics of animal research: what are the prospects for agreement?

PMID- 9924616
TI  - Painism: some moral rules for the civilized experimenter.

PMID- 9924617
TI  - Bringing both sides together.

PMID- 9924618
TI  - From vilification to accommodation: making a common cause movement.

PMID- 9924619
TI  - The role of an academic center in promoting common goals.

PMID- 9924620
TI  - The use of animals in biomedical research and teaching: searching for a common
      goal.

PMID- 9924621
TI  - Validation and regulatory acceptance of alternatives.

PMID- 9924622
TI  - Australian animal ethics committees: we have come a long way.

PMID- 9924623
TI  - On animal experimentation: Seeking common ground. CQ sources/bibliography.

PMID- 9924625
TI  - The global ethics of latex gloves: reflections on natural resource use in
      healthcare.

PMID- 9924626
TI  - Environmental ethics and medical ethics: some implications for end-of-life care,
      Part I.

PMID- 9924624
TI  - Germ-line therapy for mitochondrial disease: some ethical objections.

PMID- 9924627
TI  - Calmodulin regulation of Ca2+ entry in Jurkat T cells.
AB  - We have previously proposed a role for calmodulin (CaM) in the regulation of
      initiation of Ca2+ entry in Jurkat T cells, as well as in the regulation of the
      current that mediates Ca2+ entry, IT. In this report, we provide evidence for the
      mechanism of CaM action. We have previously shown that activation-induced Ca2+
      entry into Jurkat T cells is mediated by a current we have called IT. In the
      whole cell variation, but not the perforated patch variation, of the patch clamp
      technique, this current is short-lived (under 6 min) suggesting that the current
      is under the control of a diffusible component of the cytosol. Addition of CaM to
      the whole cell recording pipette solution maintained IT for up to 20 min,
      suggesting that CaM may be this diffusible component. Pharmacological inhibitors
      of CaM blocked the augmentation of IT normally induced by an activating stimulus.
      Cells electroporated in the presence of anti-CaM antibodies had reduced influx of
      extracellular Ca2+, with no change in release of Ca2+ from the internal stores.
      These observations suggest that T cell receptor engagement initiates Ca2+ influx
      by a pathway that likely includes CaM, which may in turn regulate IT. Influx of
      extracellular Ca2+ is required for cellular proliferation, and inhibition of CaM
      by pharmacological inhibitors reduced cellular proliferation. This same
      inhibition of proliferation was seen in cells electroporated with anti-CaM
      antibodies. This suggests that inhibition of CaM and/or IT may be a target for
      therapeutic inhibition of inappropriate T cell proliferation.

PMID- 9924628
TI  - Pituitary adenylate cyclase-activating polypeptides 38 and 27 increase cytosolic
      free Ca2+ concentration in porcine somatotropes through common and distinct
      mechanisms.
AB  - Ca2+ plays an essential role in pituitary adenylate cyclase-activating
      polypeptide (PACAP)-stimulated growth hormone (GH) secretion from porcine
      somatotropes. Here, Indo-1 microfluorimetry was used to investigate the dynamics
      of free cytosolic Ca2+ concentration ([Ca2+]i) in single porcine somatotropes in
      response to PACAP38 and PACAP27. We also evaluated the relative contributions of
      extra- and intracellular Ca2+ sources and of cAMP-dependent protein kinase (PKA)
      and phospholipase C (PLC). A high proportion of somatotropes responded to PACAP38
      (79.4%) and PACAP27 (68.4%) with [Ca2+]i rises that could be followed by a
      refractory plateau (type 1 response), or by a decrease in [Ca2+]i during which
      somatotropes were responsive to a subsequent PACAP pulse (type II response).
      Although Ca2+ profiles in response to both peptides were similar, PACAP38-induced
      [Ca2+]i rises were higher. Somatotrope response to PACAP38 or PACAP27 was
      markedly reduced by removing extracellular Ca2+, blocking Ca2+ entry through L
      type voltage sensitive Ca2+ channels (VSCC), or inhibiting PKA. Conversely, Ca2+
      depletion from intracellular stores or PLC inactivation did not affect the
      response to PACAP27 but considerably reduced maximal [Ca2+]i induced by PACAP38.
      We conclude that both peptides stimulate extracellular Ca2+ influx through L-type
      VSCC by a PKA-dependent mechanism. However, PACAP38 also triggers a PLC-mediated
      Ca2+ mobilization from intracellular stores, thereby indicating that the two
      molecular forms of PACAP activate common and distinct second messenger pathways
      within porcine somatotropes.

PMID- 9924629
TI  - Histamine causes Ca2+ entry via both a store-operated and a store-independent
      pathway in bovine adrenal chromaffin cells.
AB  - The characteristics and properties of the increase in cytosolic [Ca2+] that
      occurs in bovine adrenal medullary chromaffin cells on exposure to histamine have
      been investigated. Specifically, these experiments were conducted to determine
      how much external Ca2+ enters the cell through a (capacitative) Ca2+ entry
      pathway activated as a consequence of intracellular Ca2+ store mobilization,
      relative to that which enters independently of store depletion via other channels
      activated by histamine. In Fura-2 loaded cells continued exposure to histamine
      (10 microM) caused a rapid but transient increase in cytosolic [Ca2+] followed by
      a lower plateau that was sustained as long as external Ca2+ was present. In the
      absence of external Ca2+, only the initial brief transient was observed. In cells
      previously treated with thapsigargin (100 nM) in Ca(2+)-free medium to deplete
      the internal Ca2+ stores, histamine caused no increase in cytosolic [Ca2+] when
      external Ca2+ was absent. Re-introduction of external Ca2+ to thapsigargin
      treated store-depleted cells caused a sustained increase in cytosolic [Ca2+] that
      was further increased (P < 0.0002) upon exposure to histamine. The histamine
      evoked increase was prevented by the H1-receptor antagonist, mepyramine (2
      microM). A comparison was made between store-dependent Ca2+ entry consequent upon
      store mobilization with histamine in Ca(2+)-free medium and plateau phase Ca2+
      entry resulting from stimulation with histamine in Ca(2+)-containing medium. The
      latter was found to be approximately 3 times greater in magnitude than the former
      (P << 0.0001) at the same concentration of histamine (10 microM). It is concluded
      that histamine causes Ca2+ entry not only via a capacitative entry pathway
      secondary to internal store mobilization, but also causes substantial Ca2+ entry
      through other pathways.

PMID- 9924630
TI  - Sphingosylphosphorylcholine and sphingosine-1-phosphate mobilize cytosolic
      calcium through different mechanisms in human airway epithelial cells.
AB  - The sphingosine derivatives sphingosylphosphorylcholine (SPC) and sphingosine-1
      phosphate (S1P) caused a similar elevation of the intracellular Ca2+
      concentration ([Ca2+]i) in an immortalized airway epithelial cell line (CFNP9o-)
      incubated in Ca(2+)-free medium. The maximal effect was obtained with 2 microM
      SPC and 0.1 microM S1P and was sensitive to pre-incubation with pertussis toxin,
      indicating the involvement of a Gi/G(o) type of G protein. In Ca2+ containing
      medium, [Ca2+]i elevation by SPC was significantly higher than that by S1P, due
      to the fact that SPC was able to stimulate Mn2+ entry, whereas S1P was
      ineffective. SPC, but not S1P, caused a dose-dependent production of total
      inositol phosphates. Conversely, S1P, but not SPC, increased the level of
      phosphatidic acid. These findings suggest the presence of two distinct receptors,
      specific for SPC and S1P, respectively. Depletion of intracellular Ca2+ stores by
      SPC makes cells unable to respond to a subsequent addition of S1P. Conversely,
      cells do respond to SPC after a challenge with S1P, suggesting that the two
      receptors likely share one or more intracellular signalling component(s).

PMID- 9924631
TI  - Differential sensitivity to nickel and SK&F96365 of second messenger-operated and
      receptor-operated calcium channels in rat submandibular ductal cells.
AB  - The intracellular concentration of calcium ([Ca2+]i) of rat submandibular ductal
      cells was measured with the intracellular fluorescent dye Fura-2. Carbachol (100
      microM) and ATP (1 mM) both increased the [Ca2+]i. The late response to ATP was
      blocked by 0.5 mM Ni2+. This concentration of Ni2+ also blocked the increase of
      the [Ca2+]i and the uptake of manganese and calcium in response to 2'- and 3'-O
      (4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP, 100 microM), a specific
      agonist of P2X receptors from salivary glands. The increase of the [Ca2+]i in
      response to 2-methylthioadenosine 5'-triphosphate (2-MeSATP, 100 microM) a
      specific P2Y agonist in salivary glands or to a muscarinic agonist (carbachol)
      was not affected by 0.5 mM Ni2+. Only higher concentrations of Ni2+ (in the
      millimolar range) inhibited the uptake of extracellular calcium in response to
      carbachol. SK&F96365, a blocker of store-operated calcium channels, inhibited the
      uptake of extracellular calcium in response to carbachol without affecting the
      response to BzATP. It is concluded that at low concentrations (below 0.5 mM),
      Ni2+ inhibits the non-specific cation channel coupled to P2X receptors. The
      uptake of extracellular calcium by store-operated calcium channels is inhibited
      by higher concentrations of Ni2+ and by SK&F96365.

PMID- 9924633
TI  - Mapping of a carboxyl-terminal active site of parathyroid hormone by calcium
      imaging.
AB  - We recently showed that the C-terminal fragment PTH (52-84) effectively increases
      intracellular free calcium ([Ca2+]i) in a subset of growth plate chondrocytes not
      activated by the N-terminal PTH fragment (1-34). Here we characterize the active
      site on C-terminal PTH (52-84) with respect to calcium (Ca2+)-signaling and the
      mechanism involved by using synthetic PTH-subfragments in digital CCD ratio
      imaging experiments. Our results show amino acids 73-76 to be the core region for
      increasing [Ca2+]i. Ryanodine (1 microM), caffeine (10 mM), lithium (2 mM), or
      cyclopiazonic acid (2-5 microM), agents that interfere with intracellular Ca2+
      release, all failed to block PTH (52-84) induced [Ca2+]i increases. Depletion of
      extracellular calcium ([Ca2+]o) blocked PTH (52-84) induced [Ca2+]i increases,
      indicating a transmembrane Ca2+ influx. In contrast to voltage-gated and Ca2+
      release activated Ca2+ influx, PTH (52-84) evoked Ca2+ influx was not blocked by
      nickel (1 mM). We conclude that PTH amino acids 73-76 are essential for
      activation of a nickel-insensitive Ca2+ influx pathway in growth plate
      chondrocytes that is likely to be of relevance for matrix calcification, a key
      step in endochondral bone formation.

PMID- 9924632
TI  - cGMP production is coupled to Ca(2+)-dependent nitric oxide generation in rabbit
      parotid acinar cells.
AB  - We investigated the mechanism of guanosine 3',5'-monophosphate (cGMP) production
      in rabbit parotid acinar cells. Methacholine, a muscarinic cholinergic agonist,
      stimulated cGMP production in a dose-dependent manner but not isoproterenol, a
      beta-adrenergic receptor stimulant. Methacholine-stimulated cGMP production has
      been suggested to be coupled to Ca2+ mobilization, because intracellular Ca2+
      elevating reagents, such as thapsigargin and the Ca2+ ionophore A23187, mimicked
      the effect of methacholine. The cGMP production induced by Ca2+ mobilization has
      also been suggested to be coupled to nitric oxide (NO) generation because the
      effects of methacholine, thapsigargin and A23187 on cGMP production were blocked
      by NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric
      oxide synthase (NOS), and hemoglobin, a scavenger of nitric oxide (NO). Sodium
      nitroprusside (SNP), a NO donor, stimulated cGMP production. Furthermore,
      methacholine stimulated NO generation, and NOS activity in the cytosolic fraction
      in rabbit parotid acinar cells was exclusively dependent on Ca2+. These findings
      suggest that cGMP production induced by the activation of muscarinic cholinergic
      receptors is coupled to NO generation via Ca2+ mobilization.

PMID- 9924634
TI  - Images of Ca2+ flux in astrocytes: evidence for spatially distinct sites of Ca2+
      release and uptake.
AB  - In this study, we have developed a mathematical method to derive the Ca2+ fluxes
      underlying agonist-evoked Ca2+ waves in cultured rat cortical astrocytes.
      Astrocytes were stimulated with norepinephrine (100 nM) to evoke Ca2+ waves,
      which were recorded by measuring Fluo-3 fluorescence changes with high spatial
      and temporal resolution. Normalized fluorescence (delta F/F) was analyzed in
      discrete cellular spaces in a series of successive slices along the length of the
      cell. From these data, Ca2+ flux was then calculated using a one dimensional
      reaction-diffusion equation which utilizes the temporal and spatial derivatives
      of the fluorescence data and the diffusion coefficient of Ca2+ in the cytosol.
      This method identified distinct sites of positive flux (Ca2+ release into the
      cytosol) and of negative flux (Ca2+ removal from cytosol) and showed that in
      astrocytes, sites of Ca2+ release from stores regularly alternate with sites of
      Ca2+ removal from the cytosol. Cross correlation analysis of the two distribution
      patterns gave positive correlation at 2 microns out of phase and a negative
      correlation in phase. Thapsigargin-induced Ca2+ waves were analyzed to determine
      if the negative flux was due to Ca2+ uptake via thapsigargin-sensitive Ca2+
      pumps. Negative flux sites were still found under these conditions, suggesting
      that multiple mechanisms of Ca2+ removal from the cytosol may contribute to
      negative flux sites. This method of calculation of flux may serve as a means to
      describe the distribution of functional ion channels and pumps participating in
      cellular Ca2+ signalling.

PMID- 9924635
TI  - Passive Ca2+ binding in ventricular myocardium of neonatal and adult rats.
AB  - In this study, passive Ca2+ binding was determined in ventricular homogenates
      (VH) from neonatal (4-6 days) and adult rats, as well as in digitonin
      permeabilized adult ventricular myocytes. Ca2+ binding sites, both endogenous and
      exogenous (Indo-1 and BAPTA) were titrated. Sarcoplasmic reticulum and
      mitochondrial Ca2+ uptake were blocked by thapsigargin and Ru360, respectively.
      Free [Ca2+] ([Ca2+]F) was measured with Indo-1 and bound Ca2+ ([Ca2+]B) was the
      difference between [Ca2+]F and total Ca2+. Apparent Ca2+ dissociation constants
      (Kd) for BAPTA and Indo-1 were increased by 10-20 mg VH protein/ml (from 0.35 to
      0.92 microM for Indo-1 and from 0.20 to 0.76 microM for BAPTA) and also by
      ruthenium red in the case of Indo-1. Titration with successive CaCl2 additions
      (2.5-10 nmoles) yielded delta[Ca2+]B/delta[Ca2+]F for the sum of [Ca2+]B at all
      three classes of binding sites. From this function, the apparent number of
      endogenous sites (Ben) and their Kd (Ken) were determined. Similar Ken values
      were obtained in neonatal and adult VH, as well as in adult myocytes (0.68 +/-
      0.14 microM, 0.69 +/- 0.13 microM and 0.53 +/- 0.10 microM, respectively).
      However, Ben was significantly higher in adult myocytes than in adult VH (1.73 +/
      0.35 versus 0.70 +/- 0.12 nmol/mg protein, P < 0.01), which correspond to
      approximately 300 and 213 mumol/l cytosol. This indicates that binding sites are
      more concentrated in myocytes than in other ventricular components and that Ben
      determined in VH underestimates cellular Ben by 29%. Although Ben values in
      nmol/mg protein were similar in adult and neonatal VH (0.69 +/- 0.12), protein
      content was much higher in adult ventricle (125 +/- 7 versus 80 +/- 1 mg
      protein/g wet weight, P < 0.01). Expressing Ben per unit cell volume (accounting
      for fractional mitochondrial volume, and 29% dilution in homogenate), the passive
      Ca2+ binding capacity at high-affinity sites is approximately 300 and 176 mmol/l
      cytosol in adult and neonatal rat ventricular myocytes, respectively. Additional
      estimates suggest that passive Ca2+ buffering capacity in rat ventricle increases
      markedly during the first two weeks of life and that adult levels are attained by
      the end of the first month.

PMID- 9924636
TI  - Acute gastroenteritis.
AB  - Acute gastroenteritis represents a frequent cause of morbidity and mortality
      among children in the developing world as well as morbidity in the developed
      world. Despite the large number of potential etiologic agents, management of
      gastroenteritis is uniform and aimed to prevent the two major complications,
      dehydration and malnutrition. Current guidelines emphasize the use of oral
      rehydration and the early reintroduction of age-appropriate foods. These
      guidelines are reviewed here, the underlying principles discussed, and practical
      points provided.

PMID- 9924637
TI  - Fatal carnitine palmitoyltransferase II deficiency in a newborn: new phenotypic
      features.
AB  - We describe the term male infant of asymptomatic, healthy nonconsanguineous
      parents presenting on the first day of life with nonketotic hypoglycemia,
      seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and
      ventricular arrhythmias. Cranial ultrasound revealed cystic dysplasia with
      several foci of hyperechogenicity within the right basal ganglia. Free carnitine
      was markedly decreased in the urine and plasma with a pronounced elevation of
      plasma long-chain acylcarnitines. Fibroblast carnitine palmitoyltransferase II
      activity was reduced to 26% and 38% in the father and mother, respectively. The
      infant expired on day 5 of life from malignant ventricular tachy-arrhythmias.
      Diffuse lipid accumulation was evident at autopsy, including in the liver, heart,
      kidney, adrenal cortex, skeletal muscle, and lungs. This new case of infantile
      CPT-II deficiency illustrates the severity of the early onset form of CPT-II
      deficiency.

PMID- 9924638
TI  - Should renal ultrasonography be done routinely in children with first urinary
      tract infection?
AB  - To reassess the impact of renal ultrasonography on the care of children with
      first febrile urinary tract infection (UTI) we conducted a computer search and
      review of medical records of (1) all children who were admitted to our hospital
      with first febrile urinary tract infection and underwent renal ultrasonography
      during a 25-month period beginning February 1, 1995, (2) all children diagnosed
      by ultrasound to have hydronephrosis during the same time period. Of a total of
      124 patients with UTI, renal ultrasound appeared normal or showed evidence of
      acute pyelonephritis in 105 (84.7%), and in another nine (7.2%) it showed only
      minor findings. In 10 children (8.1%) ultrasound showed hydronephrosis and/or
      hydroureter. In eight of the latter 10, voiding cystourethrography showed
      vesicoureteral reflux; in one, posterior urethral valves; and in one, who had a
      unilateral nonobstructed dilatated system, cystography appeared normal. Except
      for the last patient, who was given prophylactic antibiotics and continued to
      have urinary tract infections, in no other case did ultrasound alone have any
      impact on the patient's management. Four children with both abnormal-appearing
      renal ultrasound and voiding cystourethrography required surgical intervention.
      One hundred of the 124 children had a voiding cystourethrogram. In 38 children it
      detected vesicoureteral reflux and, in another two, bladder abnormalities. Thirty
      five of those with abnormal-appearing cystogram but without an indication for
      surgery were given prophylactic antibiotics. During the same 25-month period, 63
      children without urinary tract infection were diagnosed by ultrasound with
      hydronephrosis. In 45 of them (71.4%) the urologic abnormality had already been
      detected by prenatal ultrasound. Fourteen of these 45 children (31.1%) required
      surgery, all for congenital anomalies related to obstructive uropathy. We
      conclude that routine renal ultrasonography in children with first urinary tract
      infection has negligible influence on their clinical management. This seems to be
      due to the recent widespread use, in industrialized countries, of maternal-fetal
      ultrasonography, which already detects a significant number of children with
      congenital obstructive uropathy prenatally. On the other hand imaging of the
      lower urinary tract is of high yield and contributes significantly to patient
      care. Therefore, whereas imaging of the lower urinary tract should continue to be
      done routinely in children with first urinary tract infection, renal ultrasound
      may be reserved for more select cases.

PMID- 9924639
TI  - Airway responsiveness to inhaled albuterol in patients with pulmonary
      hypertension.
AB  - We studied patients with pulmonary hypertension who had evidence of bronchial
      responsiveness to inhaled albuterol. The records of all patients evaluated for
      lung transplantation were reviewed: the charts of patients with pulmonary
      hypertension, either primary (PPH, n = 46) or Eisenmenger's syndrome (n = 12),
      were abstracted. Measurements of lung function revealed equal numbers of patients
      with normal, restrictive, obstructive, and mixed abnormalities. None were more
      than moderate. Airway responsiveness was defined as an increase of forced
      expiratory volume in 1 second (FEV1) > 15% or forced expiratory flow between 25%
      and 75% of the vital capacity (FEF25-75) > 25%. Of the 24 PPH and nine
      Eisenmenger's patients, 14 and four, respectively, had reversible airflow
      obstruction. These patients were more likely to have a history of atopic disease
      and to have responded to calcium channels blockers during hemodynamic monitoring.
      They did not have more severe pulmonary hypertension, as measured by hemodynamic
      monitoring. Four patients had a history of asthma, which required hospitalization
      in three. Reversible airflow obstruction occurred in half of the patients with
      pulmonary hypertension and was clinically important in at least three.

PMID- 9924640
TI  - Neonatal infrared axillary thermometry.
AB  - The authors compared axillary skin temperatures (AT) measured with an infrared
      (IR) thermometer (Lightouch Neonate, Exergen Corp) with rectal temperatures (RT)
      in 16 newly born term infants under radiant warmers (RW) and in cribs. Twelve
      stable, growing premature infants in incubators were also studied. This new
      device may be useful because of safety and rapid results (1 second), but clinical
      accuracy is unknown. For term infants, mean (SD) RT-AT difference was 0.1 (0.48)
      degree C under RW and 0.25 (0.17) degree C 2 hours later in cribs. For premature
      infants in incubators the mean RT-AT difference was 0.09 (0.16) degree C.
      Axillary temperatures measured by IR thermometer approximate RT for newly born
      term infants in cribs and stable premature infants in incubators. For newly born
      term infants under RW, RT-AT differences vary more widely, limiting clinical
      usefulness in this setting. The device, the unique age of this population, and
      the RW environment may play a role.

PMID- 9924641
TI  - Duck and take cover.

PMID- 9924642
TI  - A preterm infant with knee swelling.

PMID- 9924643
TI  - Serum leptin is elevated out of proportion to the body mass index in adolescent
      females with familial combined hyperlipidemia (FCH).

PMID- 9924644
TI  - Hypertonic 3% saline infusion by nasogastric tube for the treatment of severe
      symptomatic hyponatremia.

PMID- 9924645
TI  - Resident documentation of diagnostic impression in sexual abuse evaluations.

PMID- 9924646
TI  - Neuroradiologic review of intracranial infection.
AB  - The detection of intracranial infection continues to be a common reason for
      neuroradiologic examination. This review covers the neuroradiologic findings of
      the variety of common infections. It includes meningitis and its complications,
      as well as bacterial, viral, tuberculous, fungal, and parasitic diseases.
      Finally, a review of the common infections associated with AIDS is presented.
      With an increased ability to recognize such infections, radiologists should be
      able to supply their clinical colleagues with more specific diagnoses.

PMID- 9924647
TI  - Sexual abuse in eating disorder subtypes and control women: the role of comorbid
      substance dependence in bulimia nervosa.
AB  - OBJECTIVE: The relationship between sexual abuse and eating disorders remains
      uncertain. Recent data have raised the possibility of differential rates of
      sexual abuse among subtypes of eating disorders. METHODS: We studied women with
      three subtypes of eating disorders: (1) 26 anorexia nervosa subjects (AN); (2) 20
      bulimia nervosa subjects with comorbid substance dependence (BN + SDD); and (3)
      27 bulimia nervosa subjects without substance dependence (BN - SDD). We compared
      women with these eating disorder subtypes to 44 control women (CW). Sexual abuse
      rates and diagnoses were assessed through direct structured interviews. RESULTS:
      We found an order effect for sexual abuse which was most common (65%) in BN + SDD
      subjects, followed by a rate of 37% in BN - SDD subjects and 23% in AN subjects.
      Subjects of all eating disorder subtypes had significantly higher rates of sexual
      abuse compared to a rate of 7% in CW subjects. DISCUSSION: Women with BN + SDD
      had the highest frequency and the most severe history of sexual abuse. However,
      the causal relationship between eating disorders and sexual abuse remains to be
      elucidated.

PMID- 9924648
TI  - Are serotonin selective reuptake inhibitors effective in underweight anorexia
      nervosa?
AB  - OBJECTIVE: Recent data suggest that serotonin selective reuptake inhibiter (SSRI)
      medication is useful in preventing relapse in weight-restored anorexics. Our
      clinical impression has been that SSRIs are not effective in patients who are
      underweight with anorexia nervosa. METHOD: In order to determine whether there
      was any benefit for SSRI medication in underweight anorexics, we compared two
      groups of underweight anorexics upon admission to our inpatient hospital using a
      retrospective chart review. RESULTS: Sixty percent of anorexic patients were
      taking an SSRI upon admission to our inpatient hospital. The 24 subjects taking
      an SSRI were compared to the 16 subjects not taking an SSRI. These two groups had
      similar ages and body weights as well as scores for measures of anxiety and
      depression and most core eating disorder symptoms. DISCUSSION: These results
      suggest that SSRI medication had no effect on clinical symptoms of malnourished
      underweight anorexics.

PMID- 9924649
TI  - Effectiveness of fluoxetine therapy in bulimia nervosa regardless of comorbid
      depression.
AB  - OBJECTIVE: To evaluate fluoxetine efficacy in the treatment of bulimia nervosa
      patients with or without comorbid depression. METHOD: Two parallel, multicenter,
      double-blind, randomized, placebo-controlled fluoxetine clinical trials were
      retrospectively analyzed to determine the effect of comorbid depression on
      bulimia treatment response. Patients were stratified by their 21-item Hamilton
      Rating Scale for Depression (HAMD21) scores at baseline and by the presence or
      absence of historical or current depression. Change from baseline to endpoint in
      the number of binge eating and vomiting episodes was used to assess efficacy.
      RESULTS: Fluoxetine 60 mg treatment statistically significantly reduced (p < .05)
      the median number of binge eating and vomiting episodes. These improvements were
      independent of baseline HAMD21 score and of historical or current comorbid
      depression diagnosis. DISCUSSION: Fluoxetine 60 mg was effective in treating
      bulimia nervosa, regardless of the presence or absence of comorbid depression.
      Fluoxetine's efficacy in treating bulimia nervosa is not simply a secondary
      effect of its antidepressant properties.

PMID- 9924650
TI  - Brain glucose metabolism in eating disorders assessed by positron emission
      tomography.
AB  - OBJECTIVE: As anorectic and bulimic patients present similar clinical and
      neurobiological symptoms, the purpose of this study was to compare brain glucose
      metabolism at rest in these patients. METHODS: Positron emission tomography with
      (18-F)-fluorodeoxyglucose was used to evaluate cerebral glucose metabolism
      (CMRglu) in 10 normal-weight bulimic women, in 10 underweight anorectic patients,
      and in 10 age- and sex-matched healthy volunteers. RESULTS: Absolute global
      cortical glucose activity was significantly lower in anorectic patients compared
      with bulimic and control subjects. Anorectic patients compared with normal
      control subjects also showed higher relative CMRglu in the inferior frontal
      cortex and in the basal ganglia, and putamen and caudate relative hypermetabolism
      when compared with bulimic patients. Thus, both eating disorder groups differed
      from control subjects in low relative parietal values of glucose. DISCUSSION:
      While absolute global metabolism seems to be related to weight loss, we can
      hypothesize either a common parietal cortex dysfunction in eating disorders or a
      particular sensitivity of this cortex to consequences of eating disturbances.

PMID- 9924651
TI  - Prior treatment received by patients with bulimia nervosa.
AB  - OBJECTIVE: This study examined the frequency with which subjects with bulimia
      nervosa (BN) presenting for treatment or follow-up studies had previously
      received either adequate pharmacologic treatment or cognitive-behavioral therapy
      (CBT). METHOD: Semistructured telephone screening of individuals who called in
      response to advertisements about research studies was used to establish diagnoses
      and to clarify prior pharmacologic and psychotherapeutic treatments for BN.
      RESULTS: Of 581 women responding, 353 (60.8%) had probable BN. Overall, 61.4% of
      these subjects had received psychotherapy (96.7%) but rarely CBT (6.9%). Over one
      half (63.7%) had received pharmacologic treatment, most commonly with fluoxetine
      (72.5%). Of those having received any medication treatment, 46.2% were judged to
      have received at least one adequate trial. Overall, 35.0% of those previously
      treated had received at least one prior course of adequate pharmacotherapy or CBT
      for BN. CONCLUSION: Although efficacious treatments for BN have been established,
      they have not been received by most individuals presenting for further treatment.

PMID- 9924652
TI  - Natural course of a community sample of women with binge eating disorder.
AB  - OBJECTIVE: A community sample of women with binge eating disorder (BED) was
      followed for a period of 6 months, in order to examine the natural course of the
      disorder. METHOD: Baseline, 3-, and 6-month assessments were conducted. The
      following variables were examined: eating disorder symptomatology, importance of
      weight or shape, psychopathology, social adjustment, childhood sexual abuse,
      childhood obesity, parental obesity, and parental psychopathology. RESULTS: After
      the 3-month follow-up, 10 of the original sample of 31 participants dropped out
      of the study; drop-outs were more likely to have reported a history of sexual
      abuse. Of the 21 remaining participants, 11 continued to suffer from full
      syndrome BED at 6-month follow-up, while the remaining 10 appeared to be in
      partial remission. There were no significant baseline predictors of outcome.
      CONCLUSION: It appears that for some women with BED, the eating disorder improves
      with a decrease in binge eating and importance of weight or shape. For others,
      the eating disorder symptoms remain constant.

PMID- 9924653
TI  - Loneliness, dysphoria, dietary restraint, and eating behavior.
AB  - The study was designed to examine Herman and Polivy's restrained eating theory
      (Journal of Abnormal Psychology, 84, 666-672, 1975) using two different methods:
      situational-experimental and dispositional-correlational. Fifty-eight female
      college students were administered the revised UCLA Loneliness Scale, the Beck
      Depression Inventory (Short Form), and the Restraint scale. Subsequently, the
      students were subjected to either a neutral, sad, or loneliness mood induction
      and then ate cookies under the pretext of participating in a taste test.
      Consistent with expectation, dieters tended to consume more food in the
      loneliness than neutral mood condition, whereas nondieters displayed the opposite
      pattern. A comparable pattern was found in the relation between the revised UCLA
      Loneliness Scale and food consumption with respect to Restraint; the amount of
      food consumed increased as a function of loneliness for high restrained eaters,
      whereas the amount of food consumed decreased as a function of loneliness for low
      restrained eaters. There were no appreciable effects of the sad mood induction,
      nor prediction by dispositional depression, regarding the amount of food consumed
      as a function of dietary restraint. The findings were discussed with respect to
      the motivational role that loneliness may play in inhibiting and disinhibiting
      food consumption.

PMID- 9924654
TI  - Perfection as acculturation: psychological correlates of eating problems in
      Chinese male and female students living in the United States.
AB  - OBJECTIVE: The purpose of this study was to assess the relationship between
      acculturation, self-esteem, depression, and characteristics associated with
      eating disorders among Chinese university students in the United States. METHOD:
      A self-report questionnaire which included an acculturation scale (SL-ASIA),
      Center for Epidemiologic Studies of Depression (CES-D), Index of Self Esteem
      (ISE), and the Eating Disorders Inventory (EDI) was administered to 197 Chinese
      university students in the United States (93 females and 104 males). RESULTS:
      Highly acculturated females reported significantly higher EDI total scores, more
      maturity fears, and a greater sense of ineffectiveness. Males who were less
      acculturated also reported high ineffectiveness while high male scores on
      acculturation were associated with greater perfectionism. Overall, females
      reported more body dissatisfaction and drive for thinness, and respondents with
      high acculturation reported more perfectionism and interoceptive awareness.
      DISCUSSION: The impact of perfecting onself or one's body as a means of
      acculturating is discussed along with potential gender differences in perceived
      efficacy in a new culture.

PMID- 9924655
TI  - Body image among men and women in a biracial cohort: the CARDIA Study.
AB  - OBJECTIVE: To examine body image in a population-based, biracial cohort. METHOD:
      Body image measures were obtained on 1,837 men (45% Black) and 1,895 women (51%
      Black) in the CARDIA study. Subscales of the Multidimensional Body Self-Relations
      Questionnaire (Appearance Evaluation and Appearance Orientation) and a measure of
      body size dissatisfaction were obtained. RESULTS: Blacks were more invested in
      appearance than Whites and women were more invested than men. Women were more
      dissatisfied with size and overall appearance than men, and White men were more
      dissatisfied with appearance than Black men. Black and White women were similarly
      dissatisfied with size and appearance. However, after adjustment for age, body
      mass index, and education, Black women were more satisfied with both dimensions
      than White women. Obesity was strongly associated with body dissatisfaction
      across all gender-ethnicity groups. DISCUSSION: Significant differences in body
      image were apparent by gender and ethnicity, and different patterns were evident
      depending on the dimension considered.

PMID- 9924656
TI  - Events and the onset of eating disorders: correcting an "age old" myth.
AB  - BACKGROUND: Previous reports have suggested differences between early and late
      onset cases both in anorexia nervosa and bulimia nervosa. In anorexia nervosa,
      women with late onset are thought to be more likely to develop symptoms in
      response to life events than early onset cases. Women developing anorexia in
      response to life events are also considered to show different background
      features. In bulimia nervosa, it is not known whether rates of life events before
      onset differ in bulimics who develop their disorder at different stages in life.
      METHOD: Previously published data were reanalyzed to examine differences between
      women whose eating disorder did or did not develop in response to stress. Seventy
      two women with anorexia nervosa (48 with a severe provoking agent) and 29 women
      with bulimia nervosa (22 with a severe provoking agent) were administered
      semistructured interviews to assess life events and difficulties in the year
      before onset, childhood adversity, and other clinical features. RESULTS: In both
      anorexia nervosa and bulimia nervosa, subjects with or without a severe provoking
      agent did not differ from each other on age or childhood variables. The only
      significant difference found was that, in women developing anorexia nervosa,
      those who later developed bulimic symptoms alongside their anorexia reported a
      lower rate of provoking agents (31%) than those anorexic women who either
      maintained their restriction (76%) or went on to develop normal weight bulimia
      nervosa (69%). CONCLUSION: There are no differences between women whose eating
      disorder develops in response to stress and those who do not. Women presenting
      for treatment with anorexia nervosa of the binge-purge subtype are unlikely to
      have developed their illness in response to a severe provoking agent.

PMID- 9924657
TI  - Lesbians, bisexual women, and body image: an investigation of gender roles and
      social group affiliation.
AB  - OBJECTIVE: This study examined the effects of considering oneself to be
      masculine, feminine, or androgynous in appearance, of having friends who share
      one's gender and sexual orientation, and of affiliating with three subcommunities
      within the lesbian society on various aspects of body image. METHOD: Self-report
      measures were obtained from 188 lesbian and bisexual females. RESULTS: Feminine
      women reported lower body satisfaction than did androgynous or masculine
      identified subjects. Those whose friends shared their sexual orientation and
      gender had more positive body images than those whose friends shared only gender.
      In contrast, community affiliation was unrelated to body satisfaction.
      DISCUSSION: Within-group differences among lesbians may be central to
      understanding body image in this group.

PMID- 9924659
TI  - Interrater reliability of a Danish version of the Morgan Russell scale for
      assessment of anorexia nervosa.
AB  - OBJECTIVE: To study the interrater reliability of a Danish version of the Morgan
      Russell scale for assessment of patients with anorexia nervosa, and subsequently
      to clarify the existing rating instructions. METHOD: Ten patients undergoing
      treatment for anorexia nervosa at a regional center participated and had their
      interview videotaped. Two interviews were reserved for a training phase only. The
      group of raters comprised eight clinicians, and measures of interrater
      reliability were computed using intraclass correlation coefficient (ICC).
      RESULTS: The ICC for the total score was good (0.79), while reliability for the
      single items varied from poor to excellent (0.14-0.99). Internal consistency as
      expressed by Cronbach's coefficient alpha was acceptable (0.74). DISCUSSION: The
      Morgan Russell scale stands out as an easily applied and reliable measure of
      severity of anorexia nervosa, though the rating instructions need clarification
      in some items.

PMID- 9924658
TI  - Antioxidant status in anorexia nervosa.
AB  - OBJECTIVE: The study of the antioxidant status in female adolescents (N = 82)
      with anorexia nervosa, by the measurement of erythrocyte tocopherol
      concentration, and the determination of activities of the main antioxidant
      enzymes: superoxide dismutase, catalase, glutathione peroxidase, and glutathione
      reductase. METHOD: Tocopherol was measured by high-performance liquid
      chromatography (HPLC) with ultraviolet (UV) detection, and antioxidant enzyme
      activities by spectrometric methods using a Cobas Fara automated centrifugal
      analyzer. RESULTS: Tocopherol was significantly decreased in the anorexic
      patients compared to reference values (p < .02). In 21% of patients, tocopherol
      levels were below the reference interval. Superoxide dismutase activity was
      significantly decreased (p < .0001), while catalase activity was increased (p <
      .0001). The activity of the glutathione system enzymes did not show significant
      differences between patients and controls. DISCUSSION: The deficient
      concentration of erythrocyte tocopherol together with the altered antioxidant
      enzyme activities suggest a certain degree of oxidative damage in anorexia
      nervosa owing to both factors deficient micronutrient intake and oxidative
      stress.

PMID- 9924660
TI  - A role for Helicobacter pylori in the gastrointestinal complaints of eating
      disorder patients?
AB  - Eating disorder patients frequently present with gastrointestinal complaints.
      Helicobacter pylori is an etiologic factor in type B gastritis, gastric and
      duodenal ulcers, and may cause nausea and anorexia. OBJECTIVE: To determine
      whether or not there is an increased prevalence of H. pylori infection in
      patients with eating disorders. METHOD: Serum H. pylori IgG antibody and
      gastrointestinal symptoms were assessed in 32 patients admitted for inpatient
      treatment of anorexia nervosa and/or bulimia nervosa. RESULTS: Eating disorder
      patients did not have an increased rate of detectable serum H. pylori IgG
      antibody. DISCUSSION: There is not an increased prevalence of H. pylori infection
      in eating disorder patients. Thus, the increased frequency of gastrointestinal
      complaints in eating disorder patients cannot be attributed to H. pylori
      infection.

PMID- 9924661
TI  - Rapid recovery from anorexia nervosa after a life-threatening episode with severe
      thrombocytopenia: report of three cases.
AB  - We report the cases of three patients with anorexia nervosa (AN) who each
      recovered rapidly after experiencing a life-threatening episode with severe
      thrombocytopenia. All three cases were the typical restricting-type of AN,
      occurring in adolescence. They refused to be admitted to a hospital until their
      general condition had been severely deteriorated. Their lowest platelet counts
      were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic
      tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal
      bleeding were observed. The bone marrow examination showed apparent hypoplasia in
      two patients. No evidence of disseminated intravascular coagulation or
      autoantibody to platelets was detected. The platelet counts recovered rapidly by
      water and nutritional supplementation. The recovery from the AN itself was
      excellent in all three patients without specific psychotherapy.

PMID- 9924662
TI  - Collaboration in community based rehabilitation agencies.
AB  - One of the strategies which non-government organizations (NGOs) involved in
      Community Based Rehabilitation (CBR) use to develop their organizations and
      maximize their impact is through collaboration with other partners. A survey
      conducted by the International Centre for the Advancement of CBR identified
      collaboration styles, concerns, opportunities, and barriers among NGOs working in
      disability. Discussion focuses on differences between collaboration in
      industrialized and less developed countries; on resource dependency; and on
      structural characteristics of organizations that influence their interactions.
      The limited public concern for disability issues is viewed as a principal reason
      for the broad collaboration patterns which are seen in this field.

PMID- 9924663
TI  - Predictors of early retirement and rehabilitation for use in a screening to
      detect workers in need of rehabilitation.
AB  - In the German pension insurance sector a screening is being suggested to ensure
      the participation in rehabilitation measures of workers at risk of health-related
      early retirement. Screening presupposes empirical indicators of rehabilitation
      needs. A study is presented that determined predictors of early retirement and
      rehabilitation from longitudinal data for use in a screening for the selection of
      workers likely to be in need of rehabilitation. We gathered longitudinal data by
      conducting a second survey with a cohort for which the first survey had delivered
      clinical findings, lab. values, medical diagnoses and self reports regarding
      morbidity, medication, health-related behavior, family- and occupational-related
      strains, and sociodemographic information (first survey T0: 1975/76, n = 3.968;
      second survey T1: 1992/93, n = 28.463). The survey of T1 also comprised inquiries
      of the pension insurance institutions concerning the retirement and
      rehabilitation status for pension-insured study subjects (n = 1.794). Based on
      these subjects, using multi- and bivariate regression analysis, we determined
      those T0 variables which were significantly related to the events of early
      retirement (98 cases/357 controls), rehabilitation (127 cases/200 controls) and
      early retirement or rehabilitation (185 cases/270 controls) in the period T0-T1.
      The significant T0 variables were subsequently used for the definition of a
      selection index which measured rehabilitation need by a simple sum score (number
      of significant T0 variables present). We tested the discriminative power of this
      index for a subsample of the cohort (cases who retired early or underwent
      rehabilitation and controls). The index classified 68% of the cases correctly.
      The sensitivity reached 57% and the specificity 76%. In connection with this
      result, the long prognostic time interval (up to 17 years) has to be considered.
      In the case of screening the preselection of workers via the index would occur at
      the same time as the medical assessment of the actual need for rehabilitation. An
      earlier study showed that this would raise sensitivity and specificity of an
      index based on predictors of early retirement substantially.

PMID- 9924664
TI  - Perspectives on prognosis of soft tissue musculoskeletal disorders.
AB  - This paper reflects on the state of evidence related to the prognosis of soft
      tissue musculoskeletal disorders. Prediction of the likely clinical course,
      duration and outcomes for individuals with such disorders is an important task of
      rehabilitation clinicians. Criteria used to evaluate the validity of evidence on
      prognosis are reviewed. Application of these criteria to the literature on three
      soft tissue disorders reveals methodological weaknesses in the majority of
      existing studies. Yet strengthening the rigour of future research according to
      clinical epidemiological criteria may not capture the important factors which
      prolong disability in individuals with soft tissue injuries. Specific
      considerations related to case definitions, prognostic factors, study design,
      conceptual frameworks and study setting are recommended.

PMID- 9924665
TI  - Enhancing work outcome for three persons with traumatic brain injury.
AB  - A case study approach is used to illustrate how three survivors of severe
      traumatic brain injury were able to gain and maintain employment with the
      assistance of a supported employment programme. Emphasis on the different types
      of accommodations, including the design and implementation of compensatory
      strategies, is provided for each case. Finally, on overview of steps that can be
      taken to enhance the use of such strategies on the job is presented.

PMID- 9924666
TI  - Physical 'disability' in Bantu languages: understanding the relativity of
      classification and meaning.
AB  - The terminology related to 'physical disability' in proto-Bantu and in
      contemporary Bantu languages of Zone L are examined for a better understanding of
      African classification and meaning. The methods used in the examination include
      'words and things' and ethnographic fieldwork. In proto-Bantu, nominal classes
      are used to categorize disability as both human and non-human. Based on the
      distribution of terminology, a support for differing regional and historical
      meaning is developed. The most ancient meaning links physical disability to
      'becoming heavy' out of which variants developed. In contemporary Bantu languages
      in Zone L, the widespread use of the term -lema reemphasizes categorization in
      both human and non-human, and the use of meaning found in proto-Bantu is evident.
      However, ethnographic work in the same language area indicates that other terms
      are important to an understanding of classification and meaning related to
      physical disability in Zone L. These terms relate to sorcery or reincarnation as
      meanings attached to disability.

PMID- 9924667
TI  - Behavioural problems among visually impaired between 6 months and 5 years.
AB  - The prevalence and types of behavioural problems among legally blind children
      were assessed by employing a cohort study design in a well defined geographic
      area. One hundred and eighty two children between the ages of 6 months and 5
      years were consecutively assessed over a period of 13 years. A standardized
      ophthalmological, neurodevelopmental and physical examination, a parental
      interview and video recording were employed. Diagnostic classification was based
      on the DSM-III-R criteria (American Psychiatric Association, 1987). Behavioural
      problems were documented in 49%. In 61% of these, three disorders were
      identified: (1) overanxious (n = 14), (2) oppositional with or without attention
      deficit hyperactivity (n = 15), and avoidant with or without stereotypy (n = 26).
      The first category is associated with partial sightedness and the third with
      neurodevelopmental deficits. The prevalence of behavioural problems among blind
      children is high and therefore a careful psychological monitoring and assistance
      should be offered to them and their parents.

PMID- 9924668
TI  - A quality of life assessment package: disease specific measure for pacemaker and
      cardiac rehabilitation patients.

PMID- 9924669
TI  - Usefulness of test: manual muscle testing, goniometry, and daily activities for
      differential diagnosis of Duchenne muscular dystrophy, Becker's mild muscular
      dystrophy and Becker's severe muscular dystrophy.

PMID- 9924670
TI  - Contingent valuation as a method for measuring the effects of rehabilitation.

PMID- 9924671
TI  - Association of work attitudes and mental health with level or type of income
      support received by unemployed people with disabilities.

PMID- 9924672
TI  - Methodology of home planning within interdisciplinary team.

PMID- 9924673
TI  - The present situation of the use of hearing aids in rural areas of Sri Lanka:
      problems and future prospects.

PMID- 9924674
TI  - Efficacy of short term training in education of children with mental retardation
      to teachers of visually impaired students.

PMID- 9924675
TI  - A model for diagnostics in neurological rehabilitation: an answer to 'the
      biopsychosocial disease consequence model in rehabilitation' of Talo et al.
AB  - In 1996, Talo et al. published their comprehensive version of a bio-psycho-social
      disease consequence model in rehabilitation, which deals with 'model development
      in the Finnish "Work hardening" programme for chronic pain'. The explanations
      given here serve to check the theoretical background of this model for certain
      basic assumptions as well as for the possibility to transfer it to other fields
      of rehabilitation. This is done from the viewpoint of neurological
      rehabilitation. The starting point is the consideration that the conceptions
      underlying the ICIDH are not suitable to serve as a mainstay of a model for
      diagnostics in rehabilitation because they do not reflect essential
      characteristics of the diagnostic process which is the basis for intervention. A
      model for diagnostics in neurological rehabilitation is contrasted to that of
      Talo et al. Regarding the theoretical background this model has different
      characteristics compared to that developed by the Finnish authors. It is guided
      by the process of gaining cognition in two different ways: (1) On the assumption
      that the diagnostic process reflects the same principles basically valid for
      theory-development in science, the basis of the model are conceptions for
      description and explanation of a patient's current condition. (2) Due to a
      holistic idea of disablement these conceptions are related to the individual's
      bio-psychosocial existence. As it relates to the model developed by Talo et al.
      this one represents a type of 'meta-level'. With regard to the long-term
      objective the main interest associated with the alternative model refers to its
      implications concerning the conception of the rehabilitation process as a
      prerequisite for internal quality management.

PMID- 9924676
TI  - Social consequences of long term impairments and disabilities: conceptual
      approach and assessment of handicap.
AB  - OBJECTIVES: To present a conceptual model of disablement adapted from the WHO
      model and to conduct a pilot study with a measurement tool (LIFE-H) of the
      concepts of life habits and handicap situations. DESIGN: Content validity and
      test-retest reliability study. SETTING: General community. PARTICIPANTS: A panel
      of 12 experts of rehabilitation for the process of content validity and 49
      individuals with spinal cord disorders (adults and children) for the reliability
      study. OUTCOMES MEASURES: a person's life habits (activities of daily living and
      social roles). RESULTS: The LIFE-H questionnaire was designed to assess the
      handicap situations observed in daily life of individuals with disability. The
      experts concluded that the LIFE-H items covered most of a person's life habits
      (ADL and social roles) and that it could be used to determine the appearance of
      handicap situations. The LIFE-H total score showed a good level of reliability
      for the children and the adult samples (ICC = 0.73 and 0.74, respectively). Taken
      individually, a majority of life habit categories have shown a moderate to high
      reliability level (ICC > or = 0.50) while a few life habit categories such as the
      interpersonal relationship or nutrition showed a lower reliability level.
      CONCLUSION: The development of LIFE-H allows fulfillment of the need to determine
      the disruptions in life habits of persons with disabilities.

PMID- 9924678
TI  - Implementation of new technology for persons with mental retardation and the
      importance of staff education.
AB  - Few studies have been conducted with focus on implementation of assistive
      technology for persons with mental retardation at day centres. This study
      elucidates some of the factors affecting the implementation and also reveals the
      results from an empirical survey on education and attitudes towards usage of new
      technology by day centre staff. The importance of staff education on mental
      retardation, assistive technology, adaptation of devices and methods for training
      is stressed.

PMID- 9924677
TI  - Factors contributing to patient satisfaction with rehabilitation following
      stroke.
AB  - This study charted changes in patient satisfaction with their rehabilitative
      progress over time, and examined the relative contributions of several factors to
      satisfaction. Participants were assessed on admission to and discharge from
      rehabilitation, and six and 12 months after discharge. The study was undertaken
      in the rehabilitation unit at Repatriation General Hospital, in Adelaide, South
      Australia. Participants were 60 12-month stroke survivors who had undergone an
      inpatient rehabilitation programme. Satisfaction with progress in five areas of
      function was assessed using a five point rating scale. Functional outcome was
      assessed with the Australian ADL Index (competence and performance), lifestyle
      activities with the Frenchay Activities Index, knowledge of stroke with the
      Stroke Care Information Test, depression with the Zung Self-Rating Depression
      Scale, family functioning with the McMaster Family Assessment Device, and
      patients' expectations of rehabilitation by a qualitative assessment.
      Satisfaction with progress improved with time, particularly for dressing and
      washing, but for mobility declined after discharge. Satisfaction with progress
      was consistently influenced by the return to previous lifestyle activities,
      depression, family functioning, understanding of stroke, and clarity of
      expectations on admission to rehabilitation. It is important that the concept of
      successful rehabilitation acknowledges the perspective of the patient.

PMID- 9924679
TI  - Psychological evaluations of patients operated for idiopathic scoliosis by the
      Harrington method.
AB  - A study group of 204 patients operated for idiopathic scoliosis by the Harrington
      method at The Orthopedic Hospital of the Invalid Foundation (Orton) between 1970
      and 1975 was studied to evaluate the integration of these patients into society
      regarding work outside the home, and to evaluate the patients' adaptation to
      their illness and factors relating to this adaptation. A brief intelligence test
      was also given. The mean age at the time of the first operation was 14 years, and
      at the time of follow-up it was 33 years. Eighty-four percent of the patients
      were female. The patients completed a questionnaire, which was also sent to an
      age and gender matched control group. The results show that these patients with
      idiopathic scoliosis appear to be predominantly content with their lives. These
      scoliosis patients tend to form families later in life than the controls, and
      have fewer and less satisfying sexual relationships than the controls. These
      scoliosis patients feel that their illness has mostly influenced their
      participation in work outside the home and their partaking in physical
      activities, but these influences were slight and also influenced by education.
      The studied patients had some fears about the heredity of their illness, but only
      those dissatisfied with their lives let it influence their childbearing.

PMID- 9924680
TI  - Physical training of school children with spastic cerebral palsy: effects on
      daily activity, fat mass and fitness.
AB  - Effects of two 9-month sports programmes (four or two sessions per week) on level
      of daily physical activity (PA), fat mass (FM), and physical fitness were
      assessed in children with spastic cerebral palsy (CP; n = 20, 9.2 +/- 1.4 yr),
      randomly assigned to an experimental and control group after matching. Four
      sessions per week tended to increase PA ratio (24-h energy expenditure/sleeping
      (resting) energy expenditure) after 9 months from 1.34 +/- 0.25 to 1.55 +/- 0.18
      (P = 0.07; not different versus controls). FM increased continuously in the
      control group (after 9 months + 1.1 +/- 1.6 kg, P < 0.05), whereas the
      experimental groups showed no changes. Training (respectively four and two
      sessions) increased peak aerobic power 35% (P < 0.01; P < 0.05 versus controls)
      and 21% (P < 0.01; P = 0.17 versus controls). Results also suggest that training
      has a favourable effect on isokinetic muscle strength. No training-related
      effects were found on anaerobic power. It was concluded that although aerobic
      training has a limited effect on PA in children with CP, it may prevent
      deterioration in body composition and muscle strength. Furthermore, training has
      a favourable effect on peak aerobic power.

PMID- 9924681
TI  - Integration into work of unemployed new immigrant women from single parent
      families.
AB  - In recent years, Israel has absorbed hundreds of thousands of people from the
      former USSR. For most of them the migration constituted a situation of weighty
      pressure arising from the changes and shocks encountered in all areas of life: on
      the emotional, family, social and employment levels. One of the most prominent
      among the new immigrants is the single-parent segment, which constitutes 13.6%
      (17,750 single-parent family units) of the immigrant population, headed in the
      great majority of cases by mothers. The employment situation is particularly
      severe in the segment, owing to their special family circumstances, which make it
      difficult for them to find suitable employment. The economic implications of this
      state of affairs are grave and frequently lead to poverty. This article describes
      a project for the integration into work of unemployed female immigrants by means
      of two parallel programmes: (1) workshop for job-seeking skills; (2)
      establishment and operation of a self-help group. Both of these programmes are
      backed by a social support network that took shape during the course of the
      project. The components of the programmes are described and the findings
      consequent to their operation are presented.

PMID- 9924682
TI  - Rehabilitation hospitalism.

PMID- 9924683
TI  - Employment outcomes following spinal cord injury.

PMID- 9924684
TI  - A person with intellectual and visual disabilities achieving independent task
      performance through a self-operated instruction system.

PMID- 9924685
TI  - Correlates of stress level in Chinese mothers of a child with mental retardation.

PMID- 9924686
TI  - Quality of care on a stroke rehabilitation ward: the use of urinary incontinence
      as tracer.

PMID- 9924687
TI  - A web-based risk management and medical-legal curriculum for graduate medical
      education.
AB  - An educational Web site on the topic of risk management and medical-legal issues
      was designed. The site incorporates a 25-question multiple-choice quiz where
      resident responses were stored in a database for quantitative analysis. Residents
      who browsed the educational module scored significantly higher on the quiz (81%)
      than those who did not (62%). The authors conclude that the Web site and
      accompanying quiz database offer a practical solution for the uniform delivery of
      risk management in graduate medical education.

PMID- 9924688
TI  - How a computer-based training module for the marine medic was developed.
AB  - This article is a discussion of how a prototype Computer-based Training (CBT)
      program module was developed by a team of people representing different
      nationalities and from various professions including nursing, engineering, and
      medical graphics. Multimedia solutions that would facilitate the training of
      Marine corpsmen to perform their mission as first responder in combat incidents
      were examined. Three separate software models were evaluated. The prototype
      chosen was selected because of its simplicity, user-friendliness, and cost
      effectiveness.

PMID- 9924689
TI  - The misrepresented uterus. The progression of uterine depictions in anatomical
      atlases between the sixteenth and eighteenth centuries.
AB  - Between the sixteenth and eighteenth centuries, the depiction of the female
      uterus progressed toward greater anatomical accuracy. However, as Karen Newman
      (1996) indicates, common elements persist throughout such illustrations: the
      fetus is represented as an active inhabitant of the uterus while the female body
      is rendered as either passive or absent.

PMID- 9924690
TI  - A three-dimensional animation of the classical pathway of the complement cascade.
AB  - This paper describes the creation of a three-dimensional animation showing the
      classical pathway of the complement cascade, made in Studio Strata Pro Blitz
      (v1.75+) on the Macintosh computer. An analysis of two dimensional depictions of
      the process from the chapters of current textbooks of immunology revealed
      inconsistencies; animation was used to demonstrate how these difficulties can be
      overcome.

PMID- 9924692
TI  - Why should organizations for professionals such as biomedical communicators hold
      conferences?

PMID- 9924693
TI  - Donor-recipient polymorphism of the proteinase 3 gene: a potential target for T
      cell alloresponses to myeloid leukemia.
AB  - The curative effect of allogeneic bone marrow transplantation (BMT) is in part
      due to an alloresponse of donor lymphocytes against recipient leukemia termed the
      graft versus leukemia (GvL) effect. To identify target antigens for the GvL
      response on leukemia cells, we looked for polymorphism of proteinase 3, a primary
      granule protein overexpressed in myeloid leukemias. The study was carried out in
      10 patients with hematologic diseases and their HLA-identical marrow donors. By
      polymerase chain reaction (PCR)-single strand conformation polymorphism assay,
      followed by direct sequencing of the PCR products, we found seven DNA
      polymorphisms. One of them encodes for either an isoleucine or a valine at
      position 119 of the amino acid sequence. Peptides that span the polymorphic site,
      at amino acids 115-124, were shown to bind in vitro to the HLA-A2 molecule. We
      screened 23 HLA-A2 patients with myeloid leukemia and their HLA-identical donors
      for this polymorphism. No relapse was found in the group of 4 evaluable patients
      who possessed at least one allele absent in their donor, whereas 7 of the 15
      remaining evaluable patients relapsed. These data support the possibility that T
      cell responses to allelic differences of proteinase 3 could be used as a basis
      for designing leukemia-specific adoptive T-cell therapy in acute and chronic
      myeloid leukemias.

PMID- 9924694
TI  - HLA-A, -B, -C genotyping and expression in human nonlymphoid tumor cell lines.
AB  - A combination of molecular genotyping and protein biochemistry methods was used
      to assess the HLA-A, -B, -C genotyping and expression of six tumor cell lines.
      Four cell lines had been previously HLA typed by conventional serologic methods.
      Two could not be typed by serology because deficient in the surface expression of
      HLA-A, -B, -C molecules. As shown herein, all the 25 alleles carried by the six
      tested cell lines were typed at the DNA level. In addition, discrepancies between
      the previous serologic and the present DNA typing results were detected in 9 of
      the 21 tested serologic specificities. Typing at the protein level by isoelectric
      focusing and allele-specific monoclonal antibodies confirmed the DNA typing data.
      Our results exemplify the limits of the serologic typing procedures and
      demonstrate that molecular methods are highly desirable to conduct functional
      experiments and identify HLA losses in neoplastic cells at single allele level.

PMID- 9924695
TI  - Prolonged upregulation of the expression of HLA class I antigens and
      costimulatory molecules on melanoma cells treated with 5-aza-2'-deoxycytidine (5
      AZA-CdR).
AB  - The immunogenic potential of melanoma cells and their recognition by the host's
      cytotoxic cells depends on the presence and on the level of expression of human
      leukocyte antigen (HLA) class I antigens, costimulatory molecules and melanoma
      associated antigens (MAA), on neoplastic cells. In this study, we demonstrate
      that the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR),
      significantly (p < 0.05) enhanced the constitutive expression of HLA class I
      antigens, HLA-A1 and -A2 alleles, and of the costimulatory molecules
      intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3,
      on a panel of 12 melanoma cells. This upregulation peaked at day 4, slowly
      decreased thereafter, and returned to baseline levels 32 days after the end of
      treatment. In addition, treatment with 5-AZA-CdR induced a persistent expression
      of MAGE-1 in Mel 275 melanoma cells; this was still detectable, by reverse
      transcriptase polymerase chain reaction, 60 days after the end of treatment. In
      contrast, 5-AZA-CdR did not affect the constitutive expression of the high
      molecular weight-MAA by the melanoma cells investigated. These observations,
      together with data obtained comparing the effect of 5-AZA-CdR with that of
      interferon-gamma, strongly suggest that 5-AZA-CdR may have prospective
      therapeutic implications in active and/or passive specific immunotherapy for
      human melanoma.

PMID- 9924696
TI  - Local expression of cytokines in human colorectal carcinoma: evidence of specific
      interleukin-6 gene expression.
AB  - The expression of cytokine mRNAs in tumor tissue, normal mucosa, and peripheral
      blood mononuclear cells (PBMCs) was studied in 12 patients with colorectal cancer
      undergoing surgical resection, to characterize local immune conditions. mRNA
      transcripts for interleukin (IL)-1 beta, IL-2, IL-2-R(p55), IL-4, IL-5, IL-6, and
      IL-10 were detected using the reverse transcriptase-polymerase chain reaction (RT
      PCR) technique. IL-6 mRNA was expressed in tumor tissue in 83% of the cases but
      only in one case in normal mucosa (p < 0.001); serum levels of IL-6 did not show
      any correlation with IL-6 mRNA; IL-1 beta transcripts were present in all tumor
      tissue samples; no IL-4 expression was detected; IL-2 mRNA was only present in
      two tumors; IL-2R(p55) mRNA was found in 58% of tumors but not in normal mucosae
      (p = 0.005). The expression of IL-10 suggests that it does not play a central
      role in colorectal cancer immunosuppression, and cytokine expression in PBMCs
      indicates a different and independent activation. This study suggests a pattern
      of expression of inflammatory cytokines in the tumor microenvironment, probably
      produced by infiltrating immune cells. The absence of the specific immune
      activating cytokines, IL-2 and IL-4, could indicate an impairment of the
      anticancer immune response; IL-2R results confirm the dysregulation of the IL
      2/IL-2R activation pathway. These findings may lead to a better understanding of
      the role of cytokines and especially IL-6 at the tumor site and hence their
      importance in developing an effective immunotherapy.

PMID- 9924697
TI  - Effects of OK-432 on the proliferation and cytotoxicity of lymphokine-activated
      killer (LAK) cells.
AB  - We studied the effect of a streptococcal preparation, OK-432, on the cytotoxicity
      and the proliferation of lymphokine-activated killer (LAK) cells for use in
      adoptive immunotherapy. Peripheral blood mononuclear cells (PBMC) were derived
      from healthy donors and patients with malignant brain tumors. We divided PBMC
      into two groups; these cells then were stimulated with interleukin-2 in the
      presence or absence of OK-432. OK-432 was added only in the initial 3 days during
      the 3-week midterm culture period. Then, we compared OK-432-stimulated LAK (OK
      LAK) cells with standard LAK (sLAK) cells in terms of their rate of proliferation
      and cytotoxicity. OK-LAK cells proliferated more rapidly than sLAK cells. The
      cytotoxicity of OK-LAK cells increased, whereas that of sLAK cells decreased. We
      also investigated the phenotypic differences between these two types of LAK cells
      and found that, on day 21, the OK-LAK cells consisted mostly of CD3-CD56+ NK
      cells, whereas the sLAK cells consisted mostly of CD3+CD56- T cells. The
      difference in their level of cytotoxic potential might be explained by the
      difference of predominant phenotype.

PMID- 9924698
TI  - An in vivo model to study immunotoxin-induced vascular leak in human tissue.
AB  - Phase I/II clinical trials using ricin A chain-containing immunotoxins (RTA-ITs)
      in > 125 patients with lymphoma have established that vascular leak syndrome
      (VLS) is the dose-limiting toxicity. A similar side effect has also been
      described for other immunotoxins (ITs) and for cytokines, growth factors,
      antibodies, and chemotherapeutic agents. To better reproduce the conditions
      underlying vascular leak syndrome in patients treated with immunotoxins, human
      skin grafts were transplanted onto SCID mice and modifications in the graft were
      studied after systemic administration of a RTA-IT. Compared with mice receiving
      saline, an increase in wet/dry weight ratios of these grafts was observed in mice
      injected with RTA-IT. An increase in the permeability of the human blood vessels
      was also demonstrated by the extravasation of Carbon Black and the accumulation
      of Evans Blue dye in the graft. Taken together, these observations suggest that
      the RTA-IT can induce VLS-like manifestations. This model should facilitate the
      testing of potential inhibitors of VLS, which might reduce the toxicity of ITs
      and other therapeutic agents.

PMID- 9924699
TI  - Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic
      agents in tumor cell lines that are drug resistant due to mutated p53.
AB  - Several studies suggest that tumor necrosis factor-alpha (TNF) is able to
      overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell
      lines that are drug resistant due to a mutation in the tumor suppressor gene p53
      is unclear. Therefore, we studied the in vitro cytotoxic effects of TNF combined
      with various cytotoxic agents in a model consisting of a human ovarian cancer
      cell line containing endogenous wild-type p53 (wtp53) and sublines that were made
      drug resistant against various cytotoxic agents by transfection of several forms
      of mutated p53 (mtp53). Using the microculture tetrazolium assay, the cytotoxic
      effects of TNF alone, the cytotoxic agents VM-26, melphalan, cisplatin,
      vinblastine, paclitaxel, and mitoxantrone, plus the combined effects of 10 ng/ml
      TNF added 30 min before various concentrations of the cytotoxic agents were
      established. Compared with the control cell line (A2780/cmv), two cell lines
      transfected with mtp53 (A2780/m248 and A2780/m273) showed increased resistance
      against several cytotoxic agents but also an enhanced sensitivity to TNF.
      Interaction of TNF with the cytotoxic drugs was additive in the drug-sensitive
      control cell line as well as in the drug-resistant sublines. However, because of
      the increased sensitivity of A2780/m248 to TNF at the dose used for the
      combinations, the combination of TNF with several cytotoxic drugs reduced the
      level of resistance in A2780/m248 compared with the control cell line A2780/cmv.
      In conclusion, this study shows that addition of TNF can ameliorate resistance to
      cytotoxic agents in a subline that is drug-resistant because of mutated p53. This
      reduction in resistance by TNF is not due to synergistic interaction, but to
      collateral sensitivity to TNF.

PMID- 9924700
TI  - Evidence of a cellular immune response against sialyl-Tn in breast and ovarian
      cancer patients after high-dose chemotherapy, stem cell rescue, and immunization
      with Theratope STn-KLH cancer vaccine.
AB  - Seven ovarian and 33 breast high-risk stage II/III and stage IV cancer patients
      received high-dose chemotherapy followed by stem cell rescue. Thirty to 151 days
      after stem cell transplantation, the patients received their first immunotherapy
      treatment with Theratope STn-KLH cancer vaccine. Most patients developed
      increasing IgG anti-STn titers to a sustained peak after the fourth or fifth
      immunizations. Only one patient had elevated CA27.29 (MUC1 mucin) serum levels at
      trial entry. Five of the seven patients with preimmunotherapy elevated serum
      CA125 levels demonstrated decreasing CA125 levels during immunotherapy,
      consistent with an antitumor response. Evidence of STn antigen-specific T-cell
      proliferation was obtained from 17 of the 27 evaluable patients who received at
      least three immunotherapy treatments. Eleven of the 26 patients tested had
      evidence of an anti-STn TH1 antigen-specific T-cell response as determined by
      interferon-gamma, but not interleukin (IL)-4, production. After immunization,
      lytic activity of peripheral blood lymphocytes (PBLs) tested against a lymphokine
      activated killer (LAK)-sensitive cell line, a natural killer (NK)-sensitive cell
      line, and an STn-expressing cancer cell line (OVCAR) increased significantly. In
      vitro IL-2 treatment of the PBLs after vaccination greatly enhanced killing of
      the STn+ cancer cell line. Evidence of the development of OVCAR specific killing
      activity, over and above that seen due to LAK or NK killing, is presented. These
      studies provide the strongest evidence in humans of the development of an
      antitumor T-cell response after immunization with a cancer-associated
      carbohydrate antigen.

PMID- 9924701
TI  - Heat shock protein antibodies in sarcoma patients undergoing 41.8 degrees C whole
      body hyperthermia.
AB  - Previous in vitro studies of sarcoma and normal cell lines exposed to 41.8
      degrees C (x 60 min) demonstrated selective increased expression of members of
      the heat shock protein (HSP) family 70 on the cell surface of the sarcoma cells
      only. One implication of these data relates to the clinical application of
      targeting a stress-inducible, tumor-specific immune response. We therefore
      elected to measure immune response parameters (i.e., serum antibodies against
      HSP70i, 60, and 27) in six patients with sarcoma using a Western blot technique.
      These study patients received one to four successive 41.8 degrees C whole-body
      hyperthermia (WBH) x 60-min treatments (given every 3 weeks). We also tested the
      serum of 10 untreated healthy control subjects for the same parameters. In all
      patients, baseline HSP antibody levels were detectable; in no case did WBH result
      in an increase in HSP antibodies. The serum of one patient with sarcoma
      demonstrated a strong nonfluctuating reaction against HSP27 before and after WBH
      that had no obvious correlation; this was not observed in the sera of the control
      subjects. This study suggests that WBH does not induce a B-cell response to HSP
      family 70 antigens; these data, however, do not exclude the possibility of NK
      cell activation due to HSP antigen presentation.

PMID- 9924702
TI  - Interferon-gamma production by T lymphocytes from renal cell carcinoma patients:
      evidence of impaired secretion in response to interleukin-12.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine that enhances the cytolytic
      activity, proliferation, and interferon-gamma (IFN-gamma) production by T
      lymphocytes and natural killer cells, and has significant antitumor activity in a
      variety of murine tumor models. The induction of interferon (IFN)-gamma by IL-12
      in tumor-bearing mice plays an important role in its antitumor activity. We
      therefore examined the effects of IL-12 on IFN-gamma production by T cells
      derived from patients with renal cell carcinoma (RCC), including freshly isolated
      tumor infiltrating lymphocytes (T-TIL), matched peripheral blood T cells (T-PBL),
      and RCC-specific TIL lines. IL-12 alone induced IFN-gamma secretion by T cells
      from normal individuals and appeared to act synergistically with either IL-2 or
      anti-CD3 antibody. In contrast, it failed to stimulate significant IFN-gamma
      secretion by T-PBL and T-TIL from RCC patients. This unresponsive state in T-PBL
      appeared selective because IFN-gamma was produced when cells were stimulated with
      either phytohemagglutinin or anti-CD3 antibody. Moreover, costimulation through
      the T-cell receptor (TCR)/CD3 complex or with IL-2 made T-PBL from RCC patients
      responsive to IL-12, possibly secondary to the upregulation of IL-12R (beta
      chain). A selective loss of IL-12-dependent production of IFN-gamma was also
      consistently observed in two of three established RCC-specific TIL lines.
      Although these cell lines did not respond to any concentration of IL-12, they did
      produce IFN-gamma after ligation of the TCR/CD3 or stimulation with IL-2, IL-12
      also acted either syngeristically or additively with IL-2, anti-CD3 antibody, or
      autologous tumor cells to induce IFN-gamma production. The observed decreases in
      IFN-gamma production in response to IL-12 may have a negative effect on the
      development of T-cell immunity. The clinical importance of these findings during
      in vivo administration of IL-12 remains to be determined.

PMID- 9924703
TI  - Low-dose monoclonal antibody CC49 administered sequentially with granulocyte
      macrophage colony-stimulating factor in patients with metastatic colorectal
      cancer.
AB  - The clinical and immunologic effects of murine monoclonal antibody (mAb) CC49
      administered at a low dose sequentially with granulocyte-macrophage colony
      stimulating factor (GM-CSF) were examined. Fourteen patients with metastatic
      colorectal cancer received 1 mg of unconjugated CC49 on day 1; on day 15 they
      began 125 micrograms/m2 GM-CSF by subcutaneous injection daily for 14 days,
      followed by 7 days of rest. Another 14 days of GM-CSF were then administered,
      followed by 7 days of rest. This 56-day cycle was repeated in patients whose
      cancer did not progress. Therapy was well tolerated; adverse allergic reactions
      were not observed. Objective tumor responses were not observed. Increases in
      antiidiotypic (T2) and anti-antiidiotypic (T3) cellular responses were observed,
      as were increases in human antimouse antibody levels. In contrast, the expression
      of Fc receptors on CD14+ peripheral blood monocytes decreased. This pilot study
      demonstrates idiotypic cellular immunologic effects of antitumor murine mAb, even
      at the doses used for imaging, and supports the sequential administration of GM
      CSF as an adjuvant to mAb-based immunogens.

PMID- 9924704
TI  - Induction of immunomediated diseases by recombinant human granulocyte-macrophage
      colony-stimulating factor during cancer treatment?
AB  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is
      widely used in the treatment or prevention of neutropenia induced by cytostatic
      regimens. Recent studies with this cytokine have shown several local and/or
      systemic side effects. We herein report on four patients with different tumor
      entities receiving GM-CSF as a part of their intensified cytostatic regimen. All
      four patients developed immune phenomena (sicca syndrome, seropositive
      arthralgia, hyperthyroidism, and pneumonitis, respectively) during or after
      subcutaneous treatment with GM-CSF. Pathologic alterations in immunologic serum
      parameters as well as histopathologic findings accompanied the clinical symptoms.
      These observations suggest that the therapeutic application of GM-CSF might be
      involved in the clinical emergence of autoimmune diseases.

PMID- 9924705
TI  - JC virus and chronic lymphocyte leukemia.

PMID- 9924707
TI  - The effect of probucol on oxidized cholesterol disposition in hyperlipidaemic
      patients.
AB  - Probucol is a cholesterol-lowering and antioxidant drug that has been shown to
      inhibit or delay the progression of atherosclerosis. This antiatherosclerotic
      effect may result from the removal of oxidized cholesterol on the surface of low
      density lipoprotein (LDL). To investigate whether probucol transfers oxidized
      cholesterol from LDL to urine, urine samples were obtained from five patients
      with hypercholesterolaemia treated with 500-mg probucol orally daily and from
      five healthy controls. Using gas chromatography-mass spectrometry, we identified
      cholesteryl-6-(2,6-di-tertiary butylphenol-4)-thioether (CT) in the urine samples
      from patients with hypercholesterolaemia but not from healthy controls. This
      result suggests that probucol is hydrolysed to form 4-mercapto-2,6-di-tertiary
      butylphenol (MBP) which conjugates with cholesterol-5 alpha, 6 alpha-epoxide,
      oxidized cholesterol, resulting in the formation of CT in vivo. In addition to
      its hypolipidaemic and antioxidant actions, probucol may act to prevent
      atherosclerosis by increasing the urinary excretion of oxidized cholesterol.

PMID- 9924706
TI  - Effect of an alpha-glucosidase inhibitor (voglibose), in combination with
      sulphonylureas, on glycaemic control in type 2 diabetes patients.
AB  - A multicentre study was conducted to evaluate the effect of the alpha-glucosidase
      inhibitor, voglibose, on glycaemic control in 113 patients with type 2 diabetes
      whose blood glucose control was poor on treatment with a sulphonylurea drug. The
      patients were treated for 24 weeks with 0.6 mg voglibose, given orally three
      times daily, before a meal, together with their usual sulphonylurea drug
      treatment. In the 86 patients who completed the study, fasting plasma glucose, 2
      h post-prandial plasma glucose and haemoglobin showed statistically significant
      decreases in FPG, 2h-PPG and HbA1c compared with the baseline (P < 0.05) at
      almost all time-points during treatment. No serious adverse reactions were
      reported and there were no significant changes in mean body weights. Plasma
      glucose control was considered to be improved in 65% of patients; there were no
      adverse events in 92.9% of patients. The results suggest that the combined use of
      this alpha-glucosidase inhibitor and sulphonylurea drugs may be effective in
      controlling plasma glucose in patients with type 2 diabetes and that this
      combination might delay the onset of vascular complications in these patients.

PMID- 9924708
TI  - Right ventricular impairment in patients with chronic respiratory failure on home
      oxygen therapy--non-invasive assessment using a new Doppler index.
AB  - We evaluated the usefulness of the newly defined Doppler index combining systolic
      and diastolic myocardial performance, in assessing right-heart dysfunction in 29
      patients with chronic respiratory failure caused by old tuberculosis who were on
      24-h home oxygen therapy. We measured tricuspid inflow velocity, right
      ventricular outflow velocity, late/early diastolic peak velocities (A/E), the
      ratio between pre-ejection period and ejection time (PEP/ET), and the new index
      of systolic and diastolic myocardial performance (SDMP) calculated as
      (isovolumetric contraction time + isovolumetric relaxation time)/ejection time.
      The calculated A/E, PEP/ET and SDMP in our patients were significantly higher
      than those in age-matched healthy subjects (n = 37, mean age 67 +/- 8 years).
      There was no overlap in the SDMP index between healthy subjects and patients and
      the index was not influenced by heart rate. Our results suggest that SDMP index
      is a better marker than A/E and PEP/ET for the assessment of right-ventricular
      impairment.

PMID- 9924709
TI  - Phagocytotic activity of macrophages separated from corpus lutea of
      pseudopregnant rabbits.
AB  - Macrophage activity as indicated by phagocytosis in the corpus luteum at the
      luteolysis stage was examined in rabbits during pseudopregnancy. The day of
      induction of pseudopregnancy was regarded as day 0, and the phagocytotic activity
      of macrophages obtained from luteal tissues was examined on days 7 and 16. When
      sheep red blood cells (SRBCs) were used to assess phagocytotic activity there was
      no difference in phagocytosis between days 7 and 16 but, when sensitized SRBCs
      were used to assess phagocytotic activity, the activity of macrophages on day 16
      was more than double that on day 7 (P < 0.05). These results indicate that
      immunomediated phagocytosis of luteal macrophages is enhanced at the luteolysis
      stage (day 16). This phenomenon may contribute to the process of luteolysis.

PMID- 9924710
TI  - A comparison of plasma polymorphonuclear leucocyte elastase levels in obese and
      lean individuals.
AB  - Increased release of polymorphonuclear leucocyte (PMNL) elastase, when the PMNLs
      are activated, can damage tissues in vivo. It was postulated that PMNL elastase
      might have a tissue-remodelling effect in the body and that obese individuals
      might have less PMNL elastase activity than lean individuals. To test this
      hypothesis, plasma PMNL elastase levels were determined in 70 obese individuals
      and 30 lean normal controls. The PMNL elastase levels (determined by enzyme
      linked immunosorbent assay) in the obese group (median 36.2 ng/ml) did not differ
      significantly from those in the lean healthy controls (32.6 ng/ml; P = 0.5).

PMID- 9924711
TI  - Comparison of the efficacy, safety and tolerability of azithromycin and co
      amoxiclav in the treatment of acute periapical abscesses.
AB  - The activity, safety and tolerability of the azalide azithromycin were compared
      with those of co-amoxiclav in the treatment of acute periapical abscesses in
      adults in an open, randomized, multicentre comparative study. Patients of either
      sex, recruited from 106 dental practices in Belgium, were aged between 18 and 75
      years and had acute periapical abscesses not requiring drainage, confirmed by
      radiology. Azithromycin was administered as a 500-mg tablet orally once daily for
      3 days (n = 150) and co-amoxiclav as a 625-mg capsule three times daily, for 5-10
      days (n = 153). Both before and after treatment, masticatory pain, percussion
      pain, headache, and oedema and redness of soft tissue were graded on a four-point
      scale. Overall clinical success (cure plus improvement) was seen in 131/144 (91%)
      evaluable patients receiving azithromycin and in 142/148 (96%) receiving co
      amoxiclav (difference not significant). There was no significant difference
      between the two groups in the incidence or severity of adverse events or in the
      number of discontinuations because of adverse events.

PMID- 9924712
TI  - Lung-volume reduction in parallel with coronary heart surgery: a case report.
AB  - For patients with severe disabling emphysema, lung-volume reduction surgery has
      recently been introduced as an alternative to transplantation. Performing
      parenchyma resection from appropriate areas can improve pulmonary functions in
      selected patients having severe emphysema with a flattened diaphragm. We report
      the case of a patient, who urgently needed coronary revascularization and was
      otherwise inoperable because of severe chronic obstructive pulmonary disease
      (COPD). We carried out lung-volume reduction surgery at the same time as the
      coronary bypass.

PMID- 9924713
TI  - The impact of occupational medicine specialty practice on the injury rate and
      lost-time incidence in industry of a community.

PMID- 9924714
TI  - The factor structure of the Profile of Mood States (POMS) and its relationship to
      occupational lead exposure.
AB  - The Profile of Mood States (POMS) is an instrument composed of six mood scales
      that were developed using clinical populations. This study examines the
      replicability of the POMS factor structure in lead-smelter workers and its
      association with demographic variables and lead exposure. Four hundred sixty
      seven current and retired smelter workers completed the POMS, and a factor
      analysis was performed on the individual items. Two multiple regressions in the
      currently employed workers (n = 340) with a mean age of 40 years (range, 20-63
      years) were used to compare the relationship of the resulting POMS factors with
      demographic characteristics and two measures of occupational lead exposure:
      current blood lead level (mean, 28 micrograms/dL; range, 4-62 micrograms/dL) and
      working-lifetime integrated blood lead level (mean, 711 micrograms-yr/dL; range,
      1-1537 micrograms-yr/dL). Factor analysis produced one factor, labeled "general
      distress," that was composed mainly of items from five of the six POMS subscales
      (anger, confusion, depression, fatigue, and tension) and a second factor labeled
      "psychological adjustment." Demographic variables, including education, age, and
      alcohol use, were significantly related to the "general distress" factor score.
      After the effects of the demographic variables were accounted for, the "general
      distress" factor was significantly related to integrated blood lead level but not
      current blood lead level. Integrated blood lead level, a measure of cumulative
      lead exposure that included prior high exposure, was significantly related to the
      POMS "general distress" factor, while a current blood lead level that was
      relatively low was unrelated. As expected, POMS psychological adjustment was not
      related to lead exposure. Factor analysis did not support the use of six separate
      POMS subscales in this occupational population.

PMID- 9924715
TI  - Occupational exposure to tetrachloroethene and its effects on the kidneys.
AB  - Occupational exposure to tetrachloroethene (TCE) has been reported to cause early
      adverse effects on the kidneys. We investigated the effects of TCE exposure on
      the kidneys in 82 exposed and 19 nonexposed workers from four dry-cleaning shops
      in The Netherlands. The mean inhaled amount of TCE in the exposed group, which
      was assessed by determination of its concentration in alveolar air samples, was
      8.4 mg/m3 (range, 2.2-44.6 mg/m3). This value corresponds to a mean 8-hour time
      weighted average exposure of 7.9 mg/m3 (range, 1-221 mg/m3). A chronic dose index
      (CDI) was estimated from data on the current TCE dose and the occupational
      history of the individual subjects. The mean CDI in the exposed group was 400
      months X mg/m3 (range, 12-4882 months X mg/m3). Effects on the tubules were
      assessed with the parameters N-acetyl-beta-D-glucosaminidase, beta-galactosidase,
      alanine aminopeptidase, and retinol-binding protein (RBP) in urine. Early effects
      on the glomeruli were monitored with the parameter albumin in urine. Total
      protein in urine was determined for the general assessment of effects on the
      glomeruli and tubules. The tubular parameter RBP was increased in the exposed
      group, compared with the nonexposed group. None of the other parameters differed
      between the study groups, and none of the renal-effect parameters correlated with
      the TCE dose or the CDI. In conclusion, occupational exposure to TCE may cause a
      minor effect on the tubular RBP at exposure levels below the Dutch occupational
      exposure limit (240 mg/m3).

PMID- 9924716
TI  - Chest wall pain and possible rhabdomyolysis after chloropicrin exposure. A case
      series.
AB  - Three cases are summarized in which persistent chest wall pain, as well as
      elevations of creatine phosphokinase (CK) levels, occurred after exposure to
      chloropicrin vapor in an agricultural chemicals facility. Both the severity of
      the symptoms and the degree of biochemical abnormality appeared to follow a dose
      response relationship. Myoglobinuria, on the other hand, was not found. Elevation
      of CK after chloropicrin exposure has not previously been reported and may
      represent low-grade rhabdomyolysis. Workups performed after symptomatic
      chloropicrine exposure should include CK-level determination.

PMID- 9924717
TI  - Simultaneous p-tert-butylphenol-formaldehyde resin and p-tert-butylcatechol
      contact allergies in man and sensitizing capacities of p-tert-butylphenol and p
      tert-butylcatechol in guinea pigs.
AB  - In patients who are hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP
      F-R), it is necessary, for diagnostic, therapeutic, and preventive reasons, to
      know the identity of the primary sensitizing substances, their sensitizing
      capacities, and their crossreaction patterns. The aims of this study were to
      investigate the presence of a simultaneous p-tert-butylcatechol (PTBC) contact
      allergy in individuals who were hypersensitive to PTBP-F-R, to investigate the
      sensitizing capacity of PTBC and p-tert-butylphenol (PTBP) in guinea pigs, and to
      study any crossreaction patterns. In 294 dermatitis patients tested with PTBP-F-R
      and PTBC, there was a statistically significant over-representation of
      simultaneous test reactions. Use of the guinea pig maximization test demonstrated
      that PTBC is a strong sensitizer giving crossreactions to PTBP. PTBP, however,
      failed to induce sensitization.

PMID- 9924719
TI  - Hodgkin's disease, work, and the environment. A review.
AB  - Hodgkin's disease (HD), a lymphoma with an annual incidence in the United States
      of approximately 7500 cases, primarily affects the lymph nodes, spleen, and
      liver. The point of this article is to critically review the literature regarding
      the purported relationships between HD, certain occupations, and exposure to
      chemical agents. Attention will also be focused on recent advances in molecular
      genetics in the etiology of this ailment. A MEDLINE search was conducted to
      assess case-control and mortality evaluations that investigated links between HD
      and certain occupations and exposure to designated hazards. A review of citations
      in the Silver Platter Occupational and Environmental Medicine CD-ROM database was
      also conducted to ensure that all pertinent reports were obtained. Of the
      industries evaluated, woodworking showed the most consistent link between an
      increased risk of HD (relative risk, 1.8 to 7.2), but not all studies conducted
      showed positive associations. Although certain chemicals (ie, chlorophenols,
      pesticides) were reported as risks, no chemical was consistently and
      unambiguously linked with HD. Recent investigative work, however, points to a
      major etiological role for the Epstein-Barr virus (EBV), genetic fragments of
      which have been noted in Reed-Sternberg cells, the classic malignant cells of HD.
      The occupation most consistently associated with HD appears to be woodworking,
      although no specific chemical has been consistently linked with this lymphoma.
      The most persuasive evidence regarding the cause of HD arises from recent
      studies, including epidemiological, clinical, and genetic studies, that point to
      a major role by the EBV.

PMID- 9924718
TI  - Lung cancer and occupational risk factors in Greece.
AB  - This study estimated the proportion of lung cancer in Greece that was
      attributable to occupational exposure. Two hundred eighty-two patients with lung
      cancer and 494 controls were interviewed about their socioeconomic
      characteristics, sex, age, and occupational, smoking, and residential histories.
      Each subject was classified as exposed or unexposed to known occupational lung
      carcinogens. Because of the small number of females exposed, only males were
      included in the multivariate analyses. When the occupationally exposed subjects
      were compared with the unexposed subjects and an adjustment for smoking was made,
      the relative risk for lung cancer was 2.9 (95% confidence interval, 1.95-4.31).
      If 5% to 10% of the Greek population were occupationally exposed, the
      attributable risk would be 9.9% to 16.6%, respectively. Occupational exposures
      conferred an additional risk that was approximately threefold that of smoking
      alone. Risks increased in a dose-response fashion with increasing cigarette
      consumption.

PMID- 9924720
TI  - Incorporating an environmental/occupational medicine theme into the medical
      school curriculum.
AB  - Medical schools have been slow in teaching students how to recognize and
      intervene in occupationally and environmentally related illnesses. In this
      article, we report on the efforts at one medical school, in which an occupational
      medicine physician teamed with medical school educators developed, implemented,
      and evaluated an environmental/occupational medicine (EOM) curriculum that was
      introduced in several locations, using a thematic approach. This effort resulted
      in new EOM content being added to eight core courses in a developmental sequence
      and the creation of several elective experiences. We describe techniques and
      strategies that might be useful at other institutions in promoting the EOM theme
      and improving communication. Occupational/environmental physicians and educators
      can play leadership roles in raising interest in EOM within the medical school
      setting and in developing and implementing an EOM curriculum.

PMID- 9924721
TI  - Injuries and illnesses among hospital workers in Ohio. A study of workers'
      compensation claims from 1993 to 1996.
AB  - Occupational illnesses and injuries are common problems facing workers and
      employers. The purpose of this study was to determine the nature and extent of
      illnesses and injuries among hospital workers in Ohio. All workers' compensation
      claims for 22 hospitals in Ohio during the period 1993-1996 were reviewed. The
      majority of the claims were for sprain and strain injuries. Most of the claims
      were approved. Back injury was the leading cause of injury in both genders, and
      females reported a significantly higher percentage of back injuries. The
      incidence rates for injuries and illnesses were lower than national rates for
      other industries. Generally, there was a downward trend in the number of claims
      during the study period. A negative linear trend in injury rates by hospital size
      was detected. Our findings suggest the need for safety programs, especially in
      smaller hospitals, with the goal of preventing sprain and strain injuries.

PMID- 9924722
TI  - Disabling occupational morbidity in the United States. An alternative way of
      seeing the Bureau of Labor Statistics' data.
AB  - The United States Bureau of Labor Statistics' (BLS) annual survey of occupational
      injuries and illnesses (ASOII) is one of the most frequently utilized sources of
      data on national occupational morbidity. In 1992 the BLS introduced a new and
      expanded survey method that collects more detailed data on cases with days-away
      from-work (DAW). However, to date, the BLS has not released any official
      publication that contains a comprehensive set of crosstabulated part-of-body (BP)
      and nature-of-injury (NOI) data. To improve the understanding of national DAW
      case morbidity estimates, the study presented here utilized a special data-call
      and data-reduction strategy to identify the leading ASOII BP-NOI combinations for
      DAW cases by frequency, incidence rate, and severity (median DAW) for 1994. The
      results indicated the significance of disability associated with discrete trauma
      (ie, resulting from instantaneous or sudden events) in the US workplace. While
      morbidity associated with back pain clearly continued as the most frequent type
      of disabling case, fractures at critical anatomical sites (eg, pelvic region,
      leg, shoulder) were responsible for the most lengthy disability absences from
      work in 1994. In some instances these findings were contrary to conclusions
      typically inferred from BLS publications.

PMID- 9924723
TI  - The European perspective. New dimensions in pulmonary research.

PMID- 9924724
TI  - Control of airway function during and after exercise in asthmatics.
AB  - Control of airway function during and after exercise in asthmatics. Med. Sci.
      Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S4-S11, 1999. In asthmatics, airway
      function can be quite variable during exercise depending on the level of exercise
      intensity, the duration of exercise, and whether the exercise is at constant load
      or variable in intensity. Airway diameter can be affected by activity of
      parasympathetic and sympathetic nerves, by systemic mediators such as
      catecholamines, and by local mediators such as histamine or leukotrienes.
      Asthmatic airways are populated with more inflammatory cells than normal airways,
      and bronchoconstrictor mediator release from these cells is probably caused by
      drying of the mucosa during and after periods of increased ventilation. There are
      a few bronchodilating mediators present in both asthmatic and normal airways that
      could protect against this bronchoconstriction, including prostaglandin PGE2 and
      nitric oxide. Although it is clear that many of the inflammatory mediators play a
      role in causing bronchoconstriction after exercise, the role of either
      bronchoconstrictor or bronchodilator mediators in controlling airway function
      during exercise has yet to be resolved. In addition, the mechanical interaction
      between lung parenchyma and airways may provide a bronchodilating influence. In
      conclusion, the variability in airway function during exercise in asthmatics
      could be caused by balance among various bronchodilator and bronchoconstrictor
      mediators, but it may also reflect a mechanical effect of varying levels of
      ventilation.

PMID- 9924725
TI  - Mechanical ventilatory constraints in aging, lung disease, and obesity:
      perspectives and brief review.
AB  - Mechanical ventilatory constraints in aging, lung disease, and obesity;
      perspectives and brief review. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.),
      pp. S12-S22, 1999. One of the most difficult tasks of cardiopulmonary exercise
      testing is to determine the influence of ventilatory limitations on the
      ventilatory response to exercise. Currently there is no generally accepted method
      in which to quantify the magnitude of mechanical ventilatory constraints during
      exercise. Nor is there agreement on how to quantify maximal ventilatory capacity.
      To address these issues, this article focuses on the evaluation of mechanical
      ventilatory constraints during exercise and provides an overview of the
      mechanical ventilatory constraints that are encountered with aging, lung disease,
      and obesity.

PMID- 9924726
TI  - High altitude pulmonary edema.
AB  - High altitude pulmonary edema. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.),
      pp. S23-S27, 1999. Altitude, speed and mode of ascent, and, above all, individual
      susceptibility are the most important determinants for the occurrence of high
      altitude pulmonary edema (HAPE). This illness usually occurs only 2-5 d after
      acute exposure to altitudes above 2500-3000 m. Chest radiographs and CT scans
      show a patchy predominantly peripheral distribution of edema. Wedge pressure is
      normal at rest, and there is an excessive rise of pulmonary artery pressure (PAP)
      that precedes edema formation and appears to be a crucial pathophysiologic factor
      for HAPE. Additional factors such as an inflammatory response and/or a decreased
      fluid clearance from the lung may, however, be necessary for the development of
      this noncardiogenic pulmonary edema. Bronchoalveolar lavage in patients with
      mostly advanced HAPE shows evidence of inflammatory response with increased
      permeability. There are, however, no prospective data to decide whether the
      inflammatory response is a primary cause of HAPE or a consequence of edema
      formation. Supplemental oxygen is the primary treatment in areas with medical
      facilities whereas the treatment of choice in remote mountain areas is immediate
      descent. When this is impossible and supplemental oxygen is not available,
      treatment with nifedipine is recommended until descent is possible. Even
      susceptible individuals can avoid HAPE when they ascend slowly with an average
      gain of altitude not exceeding 300-350 m.d-1 above an altitude of 2500 m.

PMID- 9924727
TI  - Cardiopulmonary limitations to exercise in restrictive lung disease.
AB  - Cardiopulmonary limitations to exercise in restrictive lung disease. Med. Sci.
      Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S28-S32, 1999. Restrictive lung
      disease encompasses a large and diverse group of disorders characterized by a
      diminished lung volume. These disorders exhibit common pathophysiologic features
      including abnormal gas exchange caused by loss of functioning alveolar-capillary
      unit, abnormal respiratory muscle energetics caused by altered mechanical
      ventilatory function, and secondary hemodynamic and cardiac dysfunction. Impaired
      gas exchange is the most prominent exercise abnormality in interstitial lung
      disease and eventually develops in other causes of lung restriction as well.
      Measurements of diffusing capacity (DLCO) and alveolar-arterial oxygen tension
      gradient during exercise are more sensitive detectors of disease than
      measurements at rest. Excessive dead space ventilation is common in pulmonary
      parenchymal, pleural, and thoracic diseases, leading to a higher minute
      ventilation and ventilatory work during exercise. The associated increase in the
      metabolic energy requirement of respiratory muscles may exceed 50% of available
      total body oxygen delivery and result in insufficient energy delivery to
      nonrespiratory muscles that sustain locomotion. Pulmonary arterial hypertension
      develops secondarily to an increased pulmonary vascular resistance. In addition,
      diastolic filling of the ventricles during exercise may be restricted by
      pulmonary fibrosis or anatomical restriction of the pleura and thorax,
      contributing to secondary cardiac dysfunction. Examples of heart-lung interaction
      are illustrated by the patient after unilateral pneumonectomy. These
      pathophysiologic changes help explain why functional disability in these patients
      is often out proportion to the impairment in lung function.

PMID- 9924728
TI  - Exercise-induced asthma: diagnosis and treatment for the recreational or elite
      athlete.
AB  - Exercise-induced asthma: diagnosis and treatment for the recreational or elite
      athlete. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S33-S38, 1999.
      Exercise-induced asthma (EIA) is found in 10-50% of recreational and elite
      athletes, depending on the population studied. The diagnosis may be made with
      symptoms (cough, wheeze, chest tightness, etc. with exercise) and with pulmonary
      function measurements (spirometry or peak flow measurements) before and after
      exercise. Most patients respond well to pre-exercise treatment with an inhaled
      quick-acting beta agonist. Some patients require additional therapy such as pre
      exercise inhaled cromolyn, daily inhaled steroids, salmeterol, theophylline,
      leukotriene modifiers, or other agents. An occasional patient presents with the
      symptoms of EIA but responds poorly to treatment. Further investigation may lead
      to a totally different diagnosis such as vocal cord dysfunction. For most
      athletes with EIA, proper diagnosis and treatment will allow them to complete at
      any level.

PMID- 9924729
TI  - The treatment of schizophrenia: a survey of the literature. 1929.

PMID- 9924730
TI  - Behavioral rehabilitation and the reduction of aggressive and self-injurious
      behaviors with cognitively impaired, chronic psychiatric inpatients.
AB  - Aggressive behavior has been identified as a significant concern and occupational
      hazard in psychiatric inpatient settings. Several factors, including lax or
      unclear ward structure, have been identified as contributing to the exhibition of
      aggressive behavior. Token economies are effective in increasing ward structure
      and reducing aggressive behavior. This study evaluated the effects of
      rehabilitation programming, based on Gordon Paul's social learning approach
      (SLA), on rates of aggressive and self-injurious behaviors in a group of
      cognitively impaired, chronic psychiatric inpatients, compared to three long-term
      wards of similar patients. While no differences were found between the two groups
      prior to implementing SLA procedures, lower rates of aggression and self
      injurious behavior were observed at one and two years on the Paul-derived ward.
      These results support the use of Paul's approach with multiply-impaired
      psychiatric inpatients in reducing patient aggression.

PMID- 9924731
TI  - Predictors of receiving aftercare 1, 3, and 18 months after a psychiatric
      emergency room visit.
AB  - This study used logistic regression to predict the receipt of aftercare within
      one, three, and eighteen months of an emergency room visit for individuals with a
      severe mental illness. Two psychiatric history variables (had previous
      psychiatric admissions and was currently receiving outpatient treatment) and one
      system responsiveness variable (was not admitted at the index emergency room
      visit) predicted receiving aftercare at all three points in time. In general,
      variables measuring a client's psychiatric history and the responsiveness of the
      treatment system appear to be better predictors of the receipt of aftercare than
      client background variables.

PMID- 9924732
TI  - Subtyping obsessive compulsive patients by depressive symptoms: a retrospective
      pilot study.
AB  - Depression is a frequent comorbid condition in obsessive compulsive disorder
      (OCD) patients and may impact upon treatment prognosis. Identification of OCD
      "subtypes" might ultimately aid in treatment decision-making as it has in other
      psychiatric disorders. A retrospective pilot study was performed examining
      depressive and OCD symptomatology by analyzing the relation between factor scores
      on the Beck Depression Inventory (BDI) and the Maudsley Inventory (MOCI) in 41
      OCD patients. Total BDI score was significantly correlated with total MOCI score
      (r = .36, p < .02). Checking was correlated with Retarded depression (r = .30, p
      < .05). Doubting correlated with both Guilty depression (r = .48, p < .002) and
      Retarded depression (r = .37, p < .02). None of the canonical correlations were
      significant. At p < .08, the first canonical correlation approached significance.
      The data were interpreted cautiously as suggesting that some OCD patients may
      exhibit symptoms of Doubting together with Guilty depression and Retarded
      depression symptoms. These data need replication in a larger, prospective study
      design.

PMID- 9924733
TI  - HIV service provision and training needs in outpatient mental health settings.
AB  - OBJECTIVE: Despite high rates of HIV infection among people with serious mental
      illness little is known about the provision of HIV related services in outpatient
      mental health settings. This study examined HIV service provision and staff
      training needs among New York State outpatient providers. METHODS: An anonymous
      survey regarding patient characteristics, provision of routine HIV risk
      assessment, general HIV service provision, and staff training needs regarding HIV
      was sent to the directors of all New York State Office of Mental Health licensed
      and certified outpatient programs. RESULTS: Less than one-third of respondents
      stated that HIV risk assessment was performed routinely upon intake. Programs
      that served more HIV identified patients were more likely to have staff trained
      in HIV service provision. The number of identified HIV infected patients also
      influenced the frequency with which programs stated that their staff needed
      additional training in HIV risk interviewing, with clinics serving over 100 known
      HIV infected patients annually reporting the least training need and clinics
      serving between 11-50 known HIV infected patients annually reporting the most
      training need. CONCLUSIONS: It appears that clinics with large numbers of known
      HIV infected patients have mobilized to deal with the unique needs of these
      patients by providing specialty services and training staff in HIV service
      provision. However, the majority of clinics have failed to realize that severe
      mental illness is associated with behaviors that place individuals at risk of HIV
      infection or else routine HIV risk assessment would be more common.

PMID- 9924735
TI  - Is there a Neurobiology of Love? Proceedings of a conference. Stockholm, Sweden,
      August 28-31, 1996.

PMID- 9924734
TI  - Using clinical and criminal involvement factors to explain homelessness among
      clients of a psychiatric probation and parole service.
AB  - This study sought to examine the rate of homelessness and the extent to which
      lifetime homelessness was associated with clinical factors, such as diagnosis and
      treatment history; or criminal factors, such as criminal behavior and arrest
      history, among psychiatric probationers and parolees. Nearly half of the clients
      screened had experienced homelessness in their lifetime. In a logistic regression
      model to explain lifetime homelessness, significant factors were younger age,
      less education, a greater number of lifetime arrests, a schizophrenia diagnosis,
      and reporting both an alcohol and drug problem. Implications for service delivery
      with this population are discussed.

PMID- 9924736
TI  - The evolutionary antecedents to love.
AB  - Behaviors are adaptations to the physical, biotic, and social environments. Great
      diversity exists among vertebrates in reproductive behaviors and the
      neuroendocrine mechanisms underlying these behaviors. Study of this diversity
      illuminates species, population, and sex differences in hormone-brain-behavior
      relations. It also can provide insights into how and why certain neuroendocrine
      mechanisms evolved. Discoveries in evolution and ecology, neuroscience and
      endocrinology, are complementary and interrelated, and when applied in behavioral
      neuroscience, the investigator's perspective is less constrained by existing
      dogma. Naturally-occurring organisms not typically studied can be especially
      useful as their unusual adaptations illustrate alternative solutions to
      particular problems. Indeed, they 'often force one to abandon standard methods
      and standard points of view' with the result that, 'in trying to comprehend their
      special and often unusual adaptation, one often serendipitously stumbles on new
      insights' (Bartholomew, 1982). Thus, to ignore comparative research would greatly
      limit our understanding of the evolution of hormone-behavior relations. As
      Bullock (1984) admonishes, "without due consideration of the neural and
      behavioral correlates of differences between higher taxa and between closely
      related families, species, sexes, and stages, we cannot expect to understand our
      nervous systems or ourselves".

PMID- 9924737
TI  - Generic aspects of primate attachments: parents, offspring and mates.
AB  - We examine behavioral and physiological aspects of primate emotional attachments
      in the context of four relationships: infant-to-parent, parent-to-infant, and
      adult male-to-female and adult female-to-male in a monogamous New World species.
      Emotional attachments in each of these relationships show striking similarities
      at a basic functional level. The nature of these similarities suggests that they
      are produced by the same psychoneuroendocrine core, which appears to be present
      in all mammals. We also consider the development of each of kind of attachment.
      In contrast to fundamental similarities in the expression of attachment, their
      development in each case appears to be based on distinct, species-typical
      dispositions and constraints.

PMID- 9924738
TI  - Neuroendocrine perspectives on social attachment and love.
AB  - The purpose of this paper is to review existing behavioral and neuroendocrine
      perspectives on social attachment and love. Both love and social attachments
      function to facilitate reproduction, provide a sense of safety, and reduce
      anxiety or stress. Because social attachment is an essential component of love,
      understanding attachment formation is an important step toward identifying the
      neurobiological substrates of love. Studies of pair bonding in monogamous
      rodents, such as prairie voles, and maternal attachment in precocial ungulates
      offer the most accessible animal models for the study of mechanisms underlying
      selective social attachments and the propensity to develop social bonds. Parental
      behavior and sexual behavior, even in the absence of selective social behaviors,
      are associated with the concept of love; the analysis of reproductive behaviors,
      which is far more extensive than our understanding of social attachment, also
      suggests neuroendocrine substrates for love. A review of these literatures
      reveals a recurrent association between high levels of activity in the
      hypothalamic pituitary adrenal (HPA) axis and the subsequent expression of social
      behaviors and attachments. Positive social behaviors, including social bonds, may
      reduce HPA axis activity, while in some cases negative social interactions can
      have the opposite effect. Central neuropeptides, and especially oxytocin and
      vasopressin have been implicated both in social bonding and in the central
      control of the HPA axis. In prairie voles, which show clear evidence of pair
      bonds, oxytocin is capable of increasing positive social behaviors and both
      oxytocin and social interactions reduce activity in the HPA axis. Social
      interactions and attachment involve endocrine systems capable of decreasing HPA
      reactivity and modulating the autonomic nervous system, perhaps accounting for
      health benefits that are attributed to loving relationships.

PMID- 9924739
TI  - Oxytocin may mediate the benefits of positive social interaction and emotions.
AB  - During breastfeeding or suckling, maternal oxytocin levels are raised by
      somatosensory stimulation. Oxytocin may, however, also be released by nonnoxious
      stimuli such as touch, warm temperature etc. in plasma and in cerebrospinal
      fluid. Consequently, oxytocin may be involved in physiological and behavioral
      effects induced by social interaction in a more general context. In both male and
      female rats oxytocin exerts potent physiological antistress effects. If daily
      oxytocin injections are repeated over a 5-day period, blood pressure is decreased
      by 10-20 mmHg, the withdrawal latency to heat stimuli is prolonged, cortisol
      levels are decreased and insulin and cholecystokinin levels are increased. These
      effects last from 1 to several weeks after the last injection. After repeated
      oxytocin treatment weight gain may be promoted and the healing rate of wounds
      increased. Most behavioral and physiological effects induced by oxytocin can be
      blocked by oxytocin antagonists. In contrast, the antistress effects can not,
      suggesting that unidentified oxytocin receptors may exist. The prolonged latency
      in the tail-flick test can be temporarily reversed by administration of naloxone,
      suggesting that endogenous opioid activity has been increased by the oxytocin
      injections. In contrast, the long-term lowering of blood pressure and of cortisol
      levels as well as the sedative effects of oxytocin have been found to be related
      to an increased activity of central alpha 2-adrenoceptors. Positive social
      interactions have been related to health-promoting effects. Oxytocin released in
      response to social stimuli may be part of a neuroendocrine substrate which
      underlies the benefits of positive social experiences. Such processes may in
      addition explain the health-promoting effects of certain alternative therapies.
      Because of the special properties of oxytocin, including the fact that it can
      become conditioned to psychological state or imagery, oxytocin may also mediate
      the benefits attributed to therapies such as hypnosis or meditation.

PMID- 9924740
TI  - Love: an emergent property of the mammalian autonomic nervous system.
AB  - The evolution of the autonomic nervous system provides an organizing principle to
      interpret the adaptive significance of mammalian affective processes including
      courting, sexual arousal, copulation, and the establishment of enduring social
      bonds. According to the Polyvagal Theory (Porges, 1995, 1996, 1997), the well
      documented phylogenetic shift in the neural regulation of the autonomic nervous
      system passes through three stages, each with an associated behavioral strategy.
      The first stage is characterized by a primitive unmyelinated visceral vagus that
      fosters digestion and responds to threat by depressing metabolic activity.
      Behaviorally, the first stage is associated with immobilization behaviors. The
      second stage is characterized by the sympathetic nervous system that is capable
      of increasing metabolic output and inhibiting the visceral vagus to foster
      mobilization behaviors necessary for 'fight or flight'. The third stage, unique
      to mammals, is characterized by a myelinated vagus that can rapidly regulate
      cardiac output to foster engagement and disengagement with the environment. The
      mammalian vagus is neuroanatomically linked to the cranial nerves that regulate
      social engagement via facial expression and vocalization. The Polyvagal Theory
      provides neurobiological explanations for two dimensions of intimacy: courting
      and the establishment of enduring pair-bonds. Courting is dependent upon the
      social engagement strategies associated with the mammalian vagus. The
      establishment of enduring pair-bonds is dependent upon a co-opting of the
      visceral vagus from an immobilization system associated with fear and avoidance
      to an immobilization system associated with safety and trust. The theory proposes
      that the phylogenetic development of the mammalian vagus is paralleled by a
      specialized communication, via oxytocin and vasopressin, between the hypothalamus
      and the medullary source nuclei of the viscera vagus, which facilitates sexual
      arousal, copulation, and the development of enduring pair-bonds.

PMID- 9924741
TI  - Effects of early stress on adult affiliative behavior.
AB  - The recently evolved mammalian species preservative behavior as opposed to the
      ancient self preservative behavior involves parental care, nursing, social
      interaction, pair bonding and mutual defense. Gonadal steroids together with
      oxytocin are critical for this affiliative, attachment behavior. When there is
      stressful loss of control, gonadotrophins are diminished, and the self
      preservative, fight-flight catecholamine coping response takes priority. It is
      suggested that self preservation is associated with left hemispheric brain
      function and that species preservation is associated with right hemispheric
      function. Stress during infancy that is severe enough to create insecure
      attachment has a dissociative effect, disrupting right hemispheric emotional
      functioning and species preservative behavior, and a permanent bias towards self
      preservation can become an adult trait. In such a person with impaired
      affiliation, corticoid responses may be deficient. The coronary type A behavior
      pattern common in our society exhibits some of this deficiency in species
      preservative activity.

PMID- 9924742
TI  - Social isolation and cardiovascular disease: an atherosclerotic pathway?
AB  - This paper outlines two pathways through which social support can influence the
      prevention or progression of cardiovascular disease: health behaviors and
      neuroendocrine mechanisms. Its primary focus is on neuroendocrine pathways,
      reviewing data which suggest that lack of social support is etiologically related
      to coronary artery lesion development through two mechanisms: sympathetic
      adrenomedullary influences on platelet function, heart rate and blood pressure in
      the initial endothelial injury; and pituitary-adrenal cortical factors involved
      in smooth muscle cell proliferation during progression of the lesion after injury
      has taken place. It hypothesizes that the buffering effect of social support on
      the cardiovascular system is mediated primarily through mechanisms associated
      with the release of oxytocin.

PMID- 9924743
TI  - Social relationships and the management of stress.
AB  - Two different types of social relationships exist in mammalian social systems:
      dominance relationships and social bondings. This article shows that both are
      crucial for the management of stress. The following general conclusions are
      derived: (1) In stable social systems, established dominance relationships result
      in predictable behaviour. As a consequence, low positions in the hierarchy do not
      necessarily lead to enhanced endocrine stress responses. Under conditions of
      instability, however, distinct increases in the activities of the pituitary
      adrenocortical- and the sympathetic-adrenomedullary systems are found; (2) The
      ability to establish and to respect dominance relationships is a prerequisite to
      build up stable social systems. Whether this ability is realized, however,
      depends on social experiences made during behavioural development. The time
      around puberty seems to be essential for the acquisition of those social skills
      needed to adapt to unfamiliar conspecifics in a non-stressful and non-aggressive
      way; (3) Stress responses can be ameliorated by the presence of members of the
      same species. This phenomenon is called social support. In general, social
      support cannot be provided by any conspecific, but the ability to give social
      support is restricted to bonding partners. In most mammalian species mothers are
      important bonding partners for their infants. In some species bondings also occur
      between adult individuals; and (4) On a physiological level the bonding partner
      reduces the activities of the pituitary-adrenocortical- and the sympathetic
      adrenomedullary systems. On a psychological level he/she can be regarded as a
      'security-giving and arousal-reducing structure'. This is true irrespective of
      whether the bonding partner is the mother, in the case of an infant, or a male or
      a female in the case of an adult individual.

PMID- 9924744
TI  - Role of the vomeronasal input in maternal behavior.
AB  - This article reviews the role of the vomeronasal system in the induction of
      parental behavior in female and male rats, using, primarily, the sensitization
      model. The following questions are addressed: (1) Is the vomeronasal system
      sexually dimorphic? (2) Do the sex differences found in the VNS underlie those
      seen in behavior? (3) Do mechanisms, other than the classical 'organizational'
      effects of perinatal gonadal steroids, play a role in the organization of
      behavioral phenotypes in parental behavior? and (4) Does vomeronasal input play a
      role in the formation of the mother infant bond in humans? The first question has
      been answered throughout the 1980's in various studies of the organizational
      actions of postnatal exposure to gonadal steroids. The second aim has been
      addressed in a functional approach by lesion and neural activation studies. The
      experiments which lead us to consider the hypothesis that nonsteroidal factors in
      development, and specifically GABA, could account for the expression of parental
      care are reviewed. Finally, research relevant to the existence of a vomeronasal
      organ in humans and a possible pheromonal input in the formation of mother-infant
      bonds in humans is reviewed.

PMID- 9924745
TI  - Love as sensory stimulation: physiological consequences of its deprivation and
      expression.
AB  - For the present purpose, love is defined as one's having stimulation that one
      desires. The nature of the stimulation can range on a continuum from the most
      abstract cognitive, to the most direct sensory, forms. Thus, this definition of
      love encompasses having an emotional bond with a person for whom one yearns, as
      well as having sensory stimulation that one desires. We address some of the
      physiological and perceptual consequences both of having, and of not having,
      love. We propose a neural mechanism by which deprivation of love may generate
      endogenous, compensatory sensory stimulation that manifests itself as
      psychosomatic illness. In addition, we propose a neuroendocrine mechanism
      underlying sexual response and orgasm. The latter includes vaginocervical sensory
      pathways to the brain that can produce analgesia, release oxytocin, and/or bypass
      the spinal cord via the vagus nerve. We present evidence of the existence of non
      genital orgasms, which suggests that genital orgasm is a special case of a more
      pervasive orgasmic process. Through recent studies, the mechanisms and
      manifestations of love and its deprivation are becoming better understood. The
      better is our understanding of love, the greater is our respect for the
      significance and potency of its role in mental and physical health.

PMID- 9924746
TI  - Oxytocin and addiction: a review.
AB  - Neuropeptides affect adaptive central nervous system processes related to opiate
      ethanol and cocaine addiction. Oxytocin (OXT), a neurohypophyseal neuropeptide
      synthesized in the brain and released at the posterior pituitary, also is
      released in the central nervous system (CNS). OXT acts within the CNS and has
      been shown to inhibit the development of tolerance to morphine, and to attenuate
      various symptoms of morphine withdrawal in mice. In rats, intravenous self
      administration of heroin was potently decreased by OXT treatment. In relation to
      cocaine abuse, OXT dose-dependently decreased cocaine-induced hyperlocomotion and
      stereotyped grooming behavior. Following chronic cocaine treatment, the
      behavioral tolerance to the sniffing-inducing effect of cocaine was markedly
      inhibited by OXT. Behavioral sensitization to cocaine, on the other hand, was
      facilitated by OXT. OXT receptors in the CNS--mainly those located in limbic and
      basal forebrain structures--are responsible for mediating various effects of OXT
      in the opiate- and cocaine-addicted organism. Dopaminergic neurotransmission-
      primarily in basal forebrain structures--is another important biochemical
      mediator of the central nervous system effects of OXT. Tolerance to ethanol (e.g.
      hypothermia-inducing effect of ethanol) also was inhibited by OXT.

PMID- 9924747
TI  - Neurosteroids: a novel function of the brain.
AB  - Neurosteroids are synthetized in the central and peripheral nervous system,
      particularly but not exclusively in myelinating glial cells, from cholesterol or
      steroidal precursors imported from peripheral sources. They include 3-hydroxy
      delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA),
      their sulfates, and reduced metabolites such as the tetrahydroderivative of
      progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-TH PROG).
      These compounds can act as allosteric modulators of neurotransmitter receptors,
      such as GABAA, NMDA and sigma receptors. Progesterone (PROG) is also a
      neurosteroid, and a progesterone receptor (PROG-R) has been identified in
      peripheral and central glial cells. At different places in the brain,
      neurosteroid concentrations vary according to environmental and behavioral
      circumstances, such as stress, sex recognition and aggressiveness. A
      physiological function of neurosteroids in the central nervous system is strongly
      suggested by the role of hippocampal PREGS with respect to memory, observed in
      aging rats. In the peripheral nervous system, a role for PROG synthesized in
      Schwann cells has been demonstrated in the repair of myelin after cryolesion of
      the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may
      be important to study the effect of abnormal neurosteroid
      concentrations/metabolism with a view to the possible treatment of functional and
      trophic disturbances of the nervous system.

PMID- 9924749
TI  - Rapid weight gain, at least in some women, is an expression of a neuroendocrine
      state characterized by reduced hypothalamic dopaminergic tone.
AB  - A group of 17 consecutive regularly menstruating women who gained at least 5 kg
      the previous year (Group 1) was compared with a control group of similar age,
      parity and social class (Group 2). Galactorrhea was observed in 6/17 women from
      group 1 and in 1/16 women from group 2 (chi 2 4.571; p < .05). Average morning
      prolactin levels were higher in group 1 (8.15 +/- 4.92 micrograms/l) than in
      group 2 (5.29 +/- 2.48 micrograms/l; p < .05). The two groups were similar in
      their morning thyroxin, triiodothyronine, TSH, estradiol, cortisol, gastrin,
      cholecystokinin, somatostatin, oxytocin, insulin and IGF-1 levels. Leptin levels
      were significantly higher in group 1 than in group 2 (18.85 +/- 10.63
      micrograms/l vs. 10.15 +/- 6.38 micrograms/l; p < .02) but this difference could
      be attributed exclusively to the higher body mass index (BMI) of group 1
      (MANCOVA). Analysis of the distribution of basal prolactin levels in group 1
      revealed a skewed distribution due to the presence of six outliers (Barnett and
      Lewis test associated with Mahalanobis distance) whose values were higher than
      the highest value found in group 2. These outliers were henceforth considered as
      subgroup 1a, and the remnant patients in group 1 as subgroup 1b. Besides the
      expected difference in basal prolactin levels between subgroups 1a and 1b (13.72
      +/- 3.69 and 5.12 +/- 1.81 micrograms/l, respectively) and the higher frequency
      of galactorrhea in group 1a (4/6 vs. 2/11; p < .05) no other differences were
      observed in clinical or basal biochemical parameters. Following domperidone (10
      mg, i.v.) the percentual increase in prolactin (delta Prl 20'/Prl 0') was
      significantly lower in group 1 than in group 2 (23.9 + 15.2 vs. 37.0 +/- 21.2; p
      < .05). In absolute values, the prolactin rise in subgroup 1a (100.7 +/- 45.5
      micrograms/l) was significantly lower (p < .02) than that of subgroup 1b (157.3
      +/- 50.3 micrograms/l) and group 2 (152.7 +/- 34.5 micrograms/l). Group 1 (and
      each one of its two sub-groups) also differed from group 2 in a higher incidence
      of meaningful life-events the year preceding the study. This study confirms
      previous observations that recent weight gain in women is preceded by important
      life-events and is associated with galactorrhea and increased prolactin levels in
      a number of them. Besides, it provides evidence that the increased prolactin
      levels are due to reduced hypothalamic dopaminergic tone.

PMID- 9924748
TI  - Oxytocin receptor mRNA expression in rat brain: implications for behavioral
      integration and reproductive success.
AB  - The nonapeptide, oxytocin (OT), has been implicated in a wide range of
      physiological, behavioral and pharmacological effects related to learning and
      memory, parturition and lactation, maternal and sexual behavior, and the
      formation of social attachments. Specific G-protein linked membrane bound OT
      receptors mediate OTs effects. The unavailability of highly selective
      pharmacological ligands that discriminate the OT receptor from the highly
      homologous vasopressin receptors (V1a, V1b and V2 subtypes) has made it difficult
      to confirm specific effects of oxytocin, particularly in brain regions where OT
      and multiple AVP receptor subtypes may be coexpressed. Here, data on the oxytocin
      receptor (OTR) messenger ribonucleic acid (mRNA) localization in brain are
      presented in the context of a model that proposes a reproductive state-dependent
      role for steroid-hormone restructuring of neural circuits, and a role for
      oxytocin in the integration of neural transmission in pathways subserving: (1)
      steroid-sensitive reproductive behaviors; (2) learning; and (3) reinforcement. It
      is hypothesized that social attachments emerge as a consequence of a conditioned
      association between OT-related activity in these pathways and the eliciting
      stimulus.

PMID- 9924750
TI  - Is there discrimination against ethnic minorities applying to Scottish medical
      schools?

PMID- 9924751
TI  - Bodily disfigurement and its relevance in the care of patients in the NHS.

PMID- 9924752
TI  - Consensus conference on atrial fibrillation in hospital and general practice.

PMID- 9924753
TI  - HIV in Scotland--the challenge ahead.

PMID- 9924754
TI  - The management of acute headache in adults in an acute admissions unit.
AB  - There have been no previously published studies about acute admissions with
      headaches to a medical admissions ward. In our retrospective case-note study of
      all patients admitted with headaches to the acute medical admission ward of
      Ninewells Hospital, Dundee over a six-month period, there were 114 admissions
      with headache (2.4% of all admissions). CT scans were done in 68 (59.6%) and were
      abnormal in 21 patients. Twenty four patients (21.1%) had serious underlying
      causes for headaches. Predictors for CT abnormalities are discussed. Eighteen
      patients had lumbar punctures and six had abnormal results. Most patients were
      discharged after one day, nine were transferred to the neurosurgical unit and
      there were two deaths. Deficiencies in record keeping were identified as was a
      lack of precision in diagnosis. Changes in practice are needed to improve patient
      care and perhaps national guidelines are required.

PMID- 9924755
TI  - Screening for anxiety and depression in adult general medical in-patients in a
      Scottish District General Hospital.
AB  - We prospectively screened for anxiety and depression by administering the HAD
      scale to consecutive general medical patients admitted to a Scottish District
      General Hospital (DGH) over a calendar month. Age, gender, and use of
      psychotropic medications were also recorded. Of 119 patients (49 male) aged 16 to
      92 years, "Probable presence of anxiety" was recorded in 23%, and "Probable
      presence of depression" in 19%. There was no significant difference between male
      and female patients or between different age groups. Formal psychological
      management was not available on site. Sixty-seven per cent of patients with
      "Probable presence of anxiety" and 61% with "Probable presence of depression"
      received no psychotropic medications. Despite a high prevalence of psychological
      distress amongst general medical in-patients, anxiety and depression are
      consistently under-diagnosed and under-treated. Screening for psychological
      distress, followed, where indicated, by psychological and/or pharmacological
      intervention, should be a fundamental element of holistic, patient-centred care
      in general medicine.

PMID- 9924756
TI  - Is the increase in asthma prevalence occurring in children without a family
      history of atopy?
AB  - We investigated the familial associations of asthma and atopic disease in a
      population in which the prevalence of asthma and atopy is increasing. Interviewer
      administered abbreviated family history questionnaires were applied in 416
      families with a total of 1005 children ascertained through index children
      attending fracture and dressing clinics. The prevalence of reported asthma
      (22.5%), eczema (24%) and hayfever (20%) in the children was high but similar to
      previous studies in this population. Asthma was reported in 20.8% of children of
      parents without a history of asthma and 18% of children of parents without any
      history of atopic disease. Logistic regression analysis of outcomes in the index
      children showed increased risk of atopic disease associated with parental history
      of the same atopic disease. The presence of an affected sibling was associated
      with an increased risk of eczema (OR 3.04 CI 1.83-5.05) or hayfever (OR 1.79 CI
      0.97-3.3) but not asthma (OR 1.18 CI 0.66-2.08). Increasing number of siblings
      was associated with reduced risk although this was significant only for hayfever
      (OR 0.62 CI 0.41-0.86). Although the presence of affected relatives is associated
      with an increased risk of atopic disease the high prevalence of reported atopic
      disease, particularly asthma. in children of parents without a family history of
      atopic disease suggests that much of the increase in asthma prevalence is
      occurring in children without a significant genetic predisposition. Childhood
      asthma developing in what would previously have been regarded as low risk
      families may differ in its aetiology from classical atopic asthma.

PMID- 9924757
TI  - An islander with seizures.
AB  - This case describes a man with progressive refractory epilepsy whose death was
      witnessed during a seizure. Initial brain imaging was normal, but following
      prolonged episodes of non-convulsive status epilepticus, progressive right-sided
      temporal atrophy developed over a period of two years. The clinical picture and
      postmortem examination were consistent with the diagnosis of Rasmussen's
      encephalitis, a rare condition with a bleak prognosis.

PMID- 9924758
TI  - Clinical audit; who is auditing who?
AB  - Clinical audit is the principal means by which current clinical practice is
      improved. Doctors in training must gain positive experience of audit as juniors,
      so as to establish the importance of audit for future practice. Good audit
      requires involvement of doctors in training, a high level of participation and a
      leading role to be taken by the professional bodies. To examine the degree to
      which such criteria are met currently, the quality and prevalence of clinical
      audit, the participation of junior doctors in audit, and the preparedness of
      medical professional bodies' to guide audit were assessed. One hundred and twenty
      six junior and senior house officers in three Edinburgh hospitals were
      administered questionnaires in person, whilst eight Royal Colleges, the British
      medical Association and the General Medical Council were assessed by the quality
      of their written guidelines for audit. The data showed that only thirteen out of
      twenty four specialties, which employed half the juniors, utilised clinical
      audit. Half of these audit programs were structured to lead to improved patient
      care. Surprisingly, only three out of ten professional bodies were able to
      provide good quality audit information. In conclusion, clinical audit is not
      universal practice and many existing audit programs are inappropriately
      structured. Commonly, doctors at all levels seemed unaware of the goals of
      clinical audit. In addition, the majority of professional bodies provide poor
      information, thereby impeding successful audit by doctors in training. Clinical
      audit will not succeed until such deficiencies are rectified.

PMID- 9924759
TI  - Buchu--South Africa's amazing herbal remedy.
AB  - Buchu leaves and oil of buchu were used by the indigenous people of South Africa
      for hundreds of years. The medicinal use of buchu was taken up by the early Dutch
      settlers and later introduced into the pharmaceutical industry in the UK. Buchu
      preparations are now used as a diuretic and for a wide range of conditions
      including stomach aches, rheumatism, bladder and kidney infections and coughs and
      colds.

PMID- 9924760
TI  - Transfusion of the HIV-seropositive patient: immunomodulation, viral
      reactivation, and limiting exposure to EBV (HHV-4), CMV (HHV-5), and HHV-6, 7,
      and 8.

PMID- 9924761
TI  - Inactivation of viruses, bacteria, protozoa, and leukocytes in platelet
      concentrates: current research perspectives.

PMID- 9924762
TI  - Platelet surface P-selectin measurements in platelet preparations: an
      international collaborative study. Biomedical Excellence for Safer Transfusion
      (BEST) Working Party of the International Society of Blood Transfusion (ISBT).

PMID- 9924763
TI  - Laboratory measurement of fetomaternal hemorrhage and its clinical relevance.

PMID- 9924764
TI  - How understanding donor behavior should shape donor selection.

PMID- 9924765
TI  - Police perspectives on responding to mentally ill people in crisis: perceptions
      of program effectiveness.
AB  - In this study, we sampled sworn police officers from three law enforcement
      agencies (n = 452), each of which had different system responses to mentally ill
      people in crisis. One department relies on field assistance from a mobile mental
      health crisis team, a second has a team of officers specially trained in crisis
      intervention and management of mentally ill people in crisis, and a third has a
      team of in-house social workers to assist in responding to calls. Calls involving
      mentally ill people in crisis appear to be frequent and are perceived by most of
      the officers to pose a significant problem for the department; however, most
      officers reported feeling well prepared to handle these calls. Generally,
      officers from the jurisdiction with a specialized team of officers rated their
      program as being highly effective in meeting the needs of mentally ill people in
      crisis, keeping mentally ill people out of jail, minimizing the amount of time
      officers spend on these calls, and maintaining community safety. Officers from
      departments relying on a mobile crisis unit (MCU) and on police-based social
      workers both rated their programs as being moderately effective on each of these
      dimensions except for minimizing officer time on these calls where the MCU had
      significantly lower ratings.

PMID- 9924767
TI  - The role of the psychologist in crisis/hostage negotiations.
AB  - Over the past three decades, there has been a noted increase in hostage and
      barricade incidents involving perpetrators with a variety of emotional, economic,
      and political motives. A hostage incident may be defined as an incident in which
      (a) perpetrator(s) hold(s) one or more persons against their will in a location
      known to police. A barricade incident, on the other hand, is an incident without
      hostages in which a perpetrator is barricaded, also in a location known to police
      and refusing to surrender. Approximately 25 years ago, a theory of crisis/hostage
      negotiations was developed which has been continuously refined in field
      applications. This article will define the goal of crisis/hostage negotiation,
      review the history of hostage taking from biblical times to the present, review
      the utilization of psychologists and other mental health consultants by police
      crisis/hostage negotiation teams, and discuss the four roles and related
      functions of psychologists on crisis/hostage negotiation teams.

PMID- 9924766
TI  - Mental health consultant to law enforcement: Secret Service development of a
      Mental Health Liaison Program.
AB  - The Mental Health Liaison Program developed and used by the Secret Service is
      presented as a model for comprehensive, multidimensional interactions between law
      enforcement and mental health systems, with particular focus on assessing and
      preventing violent behavior. The structure of the program pairs consultants-
      psychologists and psychiatrists--with Secret Service field offices to provide (a)
      consultation regarding risk assessment and case management of individuals who
      threaten or display inappropriate interest in the President or other protectees;
      (b) training for agents on risk assessment, mental illness, and mental health
      care issues; and (c) liaison activities between the Secret Service and the mental
      health community. Practical benefits to the Secret Service are discussed to
      encourage more systematic use of broad based psychological and psychiatric
      consultation to law enforcement, with a goal of enhanced intersystem
      communication and collaboration. The need for program evaluation and outcome
      research is discussed in the context of applying the model to improve other
      mental health and law enforcement systems interactions.

PMID- 9924768
TI  - A preliminary analysis of medical futility decisionmaking: law and professional
      attitudes.
AB  - Judicial decisions reviewed in this article indicate that courts have taken two
      disparate approaches to disputes over futility of treatment. To explore whether a
      consensus on medical futility is developing among hospitals, the authors
      conducted a nationwide survey of health care professionals at hospitals.
      Respondents assigned importance ratings to factors used in recent futility
      decisions made at their institutions. The resulting importance ratings showed
      significant variation by characteristics of the institution (comparing
      respondents from for-profit, not-for-profit, and government hospitals) and by
      profession of the respondent (comparing physicians and nurses). The respondents'
      judgments endorsed three distinct strategies for making futility decisions (i.e.,
      emphasis on the patient's decision preferences, providing for the patient and
      family, and adhering to objective medical and social norms).

PMID- 9924769
TI  - Special perspective an immodest proposal: should treating mental health
      professionals be barred from testifying about their patients?
AB  - Notwithstanding ethical rules that address therapeutic and forensic role
      conflicts for psychologists and psychiatrists, overzealous patient advocacy by
      therapists, tightened reimbursement for therapy, and a growth market for forensic
      psychology and psychiatry, have led many therapists to appear willingly as
      forensic experts on behalf of their patients. Existing ethical rules, as well as
      other proposed approaches to address this problem, assume that it can be resolved
      by modest changes in existing practice that permit therapists to testify as long
      as their testimony avoids psycholegal opinions. This essay questions whether
      these modest changes can adequately address this problem and advances
      consideration of a more radical proposal to address this problem, prohibiting
      therapists from testifying about their patients.

PMID- 9924770
TI  - Consensus translational initiation sites of marine invertebrate phyla.
AB  - The efficiency of translational initiation depends upon the sequence context
      surrounding the AUG codon (1, 2, 3). A purine at position -3 contributes
      critically to context, but other neighboring nucleotides are also important.
      Nucleotide frequencies at these neighboring positions vary among distant taxa (4,
      5). We have analyzed the translational initiation sites of cnidarian, echinoderm,
      molluscan, annelid, and crustacean sequences in nucleotide sequence databases.
      These taxa conform to the pattern of a strong preference for a purine at -3, but
      the frequencies of nucleotides at neighboring positions are characteristic for
      each taxon. The consensus translational initiation sequences of the marine
      invertebrate taxa are also different from those of vertebrates and single-celled
      eukaryotes. These consensus sequences are useful guides for predicting
      translational initiation sites in cDNA clones.

PMID- 9924772
TI  - Functional significance of the co-localization of taste buds and teeth in the
      pharyngeal jaws of the largemouth bass, Micropterus salmoides.
AB  - Studies of feeding behavior in the largemouth bass, Micropterus salmoides,
      revealed that live goldfish or artificial food balls are ingested in three
      discrete steps: inhalation of the food into the oral cavity, passage through the
      pharyngeal cavity, and swallowing. Food balls with or without a feeding stimulant
      were inhaled with equal frequency; thus, vision was clearly the major sense
      affecting inhalation. However, food balls with defined concentrations of a
      feeding stimulant were swallowed in a dose-dependent manner, whereas food balls
      without a feeding stimulant were promptly expelled. Thus, gustation played a
      major role in stimulating swallowing. Videotaped observations of feeding behavior
      suggested that both food processing and gustation occur in the pharynx and take
      place before the swallowing of either goldfish or food balls. The well-developed
      pharyngeal jaws of largemouth bass consist of six major pads of caniform teeth in
      the upper pharynx and two pads in the lower pharynx. Scanning electron microscopy
      showed that taste buds were abundant around most of these pharyngeal teeth.
      Histological sections prepared from all pharyngeal pads revealed that both
      elevated and flattened taste buds occur with the teeth. The morphology of these
      taste buds was typical of that described in other teleosts. Neuronal profiles,
      visualized with an HNK-1 monoclonal antibody, were observed entering each taste
      bud. The antibody also selectively stained a group of one to four putative
      sensory cells in each taste bud and the distal processes of these cells in the
      receptor area. The co-localization of teeth and taste buds on the pharyngeal jaws
      indicates that food processing and gustation both occur there, and that together
      these processes determine whether a potential food item is swallowed.

PMID- 9924774
TI  - Reproduction-associated immunoreactive peptides in the nervous systems of
      prosobranch gastropods.
AB  - Antibodies against reproductive peptides of Aplysia and Lymnaea were used to
      localize homologous immunoreactive peptides in the nervous systems of three
      prosobranch species: Busycon canaliculatum, Concholepas concholepas, and Tegula
      atra. Positive control experiments in L. stagnalis demonstrated the broad species
      range of the anti-egg-laying hormone (anti-ELH) antibody used in this study, and
      showed binding of anti-alpha-caudodorsal-cell peptide (anti-alpha-CDCP) to the
      same cells in cerebral and buccal ganglia. Dot immunoassays with synthetic ELH
      confirmed the reactivity and sensitivity (< 0.1 microgram) of the anti-ELH
      antibody. Experiments with preadsorbed antibody or no primary antibody confirmed
      its specificity. In B. canaliculatum, clusters of more than 300 neuronal cell
      bodies immunoreactive to both anti-ELH and anti-alpha-CDCP were observed along
      the medial margins of left and right cerebral ganglia. Anti-alpha-CDCP reacted
      with additional small populations of cerebral ganglion neurons not stained by
      anti-ELH. Anti-ELH and anti-alpha-CDCP also reacted with overlapping but
      different small populations of neurons in buccal ganglia. In C. concholepas and T
      atra, ELH-like immunoreactivity was found in cerebral ganglia, and in T. atra in
      fibers in the cerebral ganglia and cerebral-pedal connectives. Thus, cerebral
      ganglia are the major locus of the ELH-like immunoreactivity in prosobranchs.

PMID- 9924775
TI  - Late postembryonic development of the symbiotic light organ of Euprymna scolopes
      (Cephalopoda: Sepiolidae).
AB  - The symbiotic light organ of the sepiolid squid Euprymna scolopes undergoes
      significant anatomical, morphological, and biochemical changes during
      development. Previously we described the embryonic organogenesis and early
      postembryonic development of the light organ. During embryogenesis, tissues are
      developed that will promote the onset of an association with Vibrio fischeri, the
      light organ symbiont. Upon inoculation, and in response to the first interactions
      with the bacterial symbionts, the light organ undergoes a dramatic morphogenesis
      during the first 4-5 days of postembryonic development. Here we describe the
      final developmental stage of the light organ system, a period of late
      postembryonic development in which particular tissues of the light organ mature
      that eventually mediate the functional symbiosis. The maturation of the light
      organ occurs within 1 to 2 weeks posthatch and entails two principal processes:
      (1) changes in the shape of the organ and elaboration of the accessory tissues
      that modify the bacterially produced light; and (2) branching of the epithelial
      crypts, where the bacterial symbionts reside, and restriction of epithelial cell
      proliferation to the deepest branches of the crypts. The gross morphological
      changes of the organ occur in the absence of V. fischeri, although rudiments of
      the ciliated field of the hatchling remain in animals not exposed to the
      microbial symbiont.

PMID- 9924777
TI  - Axial patterning in the leech: developmental mechanisms and evolutionary
      implications.

PMID- 9924778
TI  - Hox genes in arthropod development and evolution.

PMID- 9924779
TI  - Heterochronic genes in development and evolution.

PMID- 9924780
TI  - A common theme for LIM homeobox gene function across phylogeny?

PMID- 9924782
TI  - Prediction of height from percutaneous tibial length amongst Oriya population.
AB  - Establishing individuality on the mutilated part of a dead body is quite a
      difficult work in forensic medicine. Among the factors required, to establish
      individuality of an unidentified dead body or any mutilated part of such dead
      body, height is one of them. In the present work an attempt has been made to
      calculate the height from the percutaneous tibial length (PCTL) as measured by
      surface anatomical landmarks that is between the most prominently palpable part
      of the medial condyle of tibia and tip of the medial malleolus. To find out the
      relationship of PCTL with that of the height and to evolve a regression equation
      formula necessary statistical evaluation has been done on the data obtained from
      1,000 adult individuals comprising of 500 males and 500 females. By using the
      regression equation formula so derived the height of an individual can be
      calculated by the help of PCTL, when only the mutilated ley portion is available
      for autopsy examination.

PMID- 9924783
TI  - Fatalities from black powder percussion handguns.
AB  - Three suicides and one homicide from black powder muzzle loading handguns are
      reported and the muzzle velocities of two weapons are recorded. The fatal head
      shots caused wide wound tracts traversing the brains and intracerebral
      haemorrhages remote from the tract were present in every case. The skulls showed
      considerable fractures which were pronounced in the cases of contact shots but
      were also present when the range of fire was 5 m. These extensive injuries from
      soft lead spheres with muzzle velocities of only approximately 200 m/s are
      attributed to the expansion of the spheres. The regularly occurring deformation
      resulted in 13-16 mm calibre missiles in the cases of .44 spheres. The special
      features of black powder such as incomplete and slow combustion resulted in
      intense soot deposits in the vicinity of the entrance wound and in long ranges
      the gunshot residues travelled. In contact shots, large pocket-like underminings
      even in deeper tissue layers, abundant soot along the trajectory and skin burns
      were observed.

PMID- 9924785
TI  - Polymorphic sites in human mitochondrial DNA control region sequences: population
      data and maternal inheritance.
AB  - Sequence analysis of the mitochondrial DNA (mtDNA) control region is of central
      importance for forensic identity testing as well as for studies of human
      evolution. Here we report the sequencing data of the hypervariable regions I and
      II from 50 unrelated individuals from a western German population (Rhine area).
      In regions I and II, 52 and 26 sites of sequence polymorphism, respectively, were
      noted. Nucleotide substitution rather than insertion/deletion was the majority of
      variation. The distribution showed a large bias towards transitional changes than
      transversional changes. Furthermore we investigated uniparental inheritance in
      seven CEPH families each family with 7-9 maternal descendants. Most maternal
      relatives shared identical mtDNA sequences. Additionally sequences were compared
      for father:child pairs and as expected no evidence for paternal transmission of
      mtDNA was observed. The high variability of mtDNA control region sequences
      permits utility in forensic identity investigations. The data also indicate that
      the neomutation rate seems to be very low from one generation to the other.

PMID- 9924784
TI  - Random amplified polymorphic DNA (RAPD) typing of necrophageous insects (Diptera,
      Coleoptera) in criminal forensic studies: validation and use in practice.
AB  - To permit quick identification of arthropods, random amplified polymorphic DNA
      typing (RAPD) was used to support classical morphological and medico-legal
      analysis of maggots on a human corpse. The method was employed to determine if
      maggots which were found on the inside of a body bag were identical (a) with
      maggots found on the outside of the bag, and (b) pupae found on the floor under
      the corpse. Pre-mixed RAPD reaction beads together with semiautomatic computer
      aided analysis of the PCR products are shown to discriminate between closely
      related necrophageous insect species (flies and beetles) found on corpses. From
      the 11 RAPD primers used, one alone was sufficient in resolving a practical
      forensic situation. This is the first report of a forensic application of RAPD
      DNA typing.

PMID- 9924786
TI  - Fluorescent multiplex analysis of nine STR loci: Spanish population data.
AB  - A total of 171 Caucasians living in Andalucia (southern Spain) have been typed
      for nine short tandem repeat (STR) loci by multiplex PCR amplification using a
      commercially available kit (Profiler Plus; Perkin-Elmer, Norwalk, CT, USA) and
      semi-automatic electrophoresis (ABI Prism 377 DNA Sequencer, Applied Biosystems,
      Foster City, CA, USA). The kit enables typing of the STR loci D3S1358, VWA, FGA,
      D5S818, D13S317, D7S820, D8S1179, D21S11, and D18S51. All loci, except D7S820,
      meet Hardy-Weinberg equilibrium. Because of the large number of loci that can be
      analyzed, the power of discrimination (PD) is greater than 0.99999, and the
      probability of exclusion (PE) reaches 0.99991 in our population sample.

PMID- 9924787
TI  - GPT genotyping by polymerase chain reaction and restriction fragment length
      polymorphism analysis.
AB  - Polymorphism of GPT was investigated in blood samples from 241 unrelated Japanese
      individuals by PCR-RFLP analysis. Three common types were identified which agreed
      with those obtained by starch gel electrophoresis. The allele frequencies were
      GPT*1 = 0.604 and GPT*2 = 0.396. The population data fitted the Hardy-Weinberg
      law. The PCR-RFLP patterns of GPT were also demonstrated in semen, and the types
      coincided with those in the corresponding blood. The present method permitted GPT
      genotyping in bloodstains and semen stains stored for 20 years. The GPT system
      determined by PCR-RFLP can still be a useful supplement in medicolegal
      individualization of biological stains.

PMID- 9924788
TI  - Report of the European DNA Profiling Group (EDNAP)--an investigation of the
      hypervariable STR loci ACTBP2, APOAI1 and D11S554 and the compound loci D12S391
      and D1S1656.
AB  - This paper describes the results of three collaborative exercises which continues
      the EDNAP theme to explore whether uniformity of DNA profiling results could be
      achieved between European laboratories using STRs. In an earlier exercise,
      complex hypervariable AAAG-repeat STR loci were investigated, but reproducibility
      was found to be poor because of the variation of techniques used by participating
      laboratories. In the exercise reported here, an internal allelic ladder composed
      of ACTBP2 and D11S554 fragments was distributed. This ladder was used to size
      ACTBP2 analysed by a "singleplex" PCR amplification and D11S554 combined with
      APOAI1 in a separate "duplex" reaction. Laboratories were asked to test 7 blood
      stains, one of which was a known control, and to report the results to the co
      ordinating laboratory. The exercise demonstrated that ACTBP2 showed good
      reproducibility between laboratories, whereas further testing would be needed to
      validate APOAI1 and D11S554 for interlaboratory comparisons. In separate
      exercises, the simple loci D12S391 and D1S1656 were tested; both of these showed
      excellent reproducibility between laboratories.

PMID- 9924789
TI  - Molecular evidence against phylogenetically distinct host races of the pea aphid
      (Acyrthosiphon pisum).
AB  - Pea aphid (Acyrthosiphon pisum) clones have been shown to be adapted to
      particular host plant species but it is unknown whether there are host races. A
      1101 base pair region of the mitochondrial cytochrome oxidase I gene (COI) was
      sequenced for 21 pea aphid clones that had been collected from different host
      plants in Canada and the U.S.A. Only five closely related mitochondrial
      haplotypes were found. A maximum likelihood phylogeny was estimated for these
      five haplotypes and four related aphid species: Acyrthosiphon macrosiphum, A.
      kondoi, Fimbriaphis fimbriata, and Macrosiphum creelii. Pea aphids from the same
      host plant species were no more likely to have the same mitochondrial haplotype
      than aphids from different host plant species. In addition, aphids from the same
      geographical regions were no more likely to have the same mitochondrial haplotype
      than aphids from different geographic regions. I therefore reject the hypothesis
      that there are monophyletic host races of the pea aphid.

PMID- 9924790
TI  - Nonallelic noncomplementation models in mice: the first arch and lidgap-Gates
      mutations.
AB  - We tested for complementation between two Mendelian mutations in mice, Far (first
      arch) and lgGa (lidgap-Gates). Each of these mutations gives greater than 70%
      risk of the birth defect, open eyelids, in homozygotes and gives little or no
      risk in heterozygotes. Far and lgGa are known to not be alleles; Far maps to Chr
      2 and lgGa maps to Chr 13. However the cross between +/Far (on the BALB/cGaBc
      strain) and lgGa/lgGa (on the LGG/Bc strain) gave 32% (48/149) of progeny
      affected with open eyelids at birth: 63% (45/71) of the double heterozygote,
      +/Far, +/lgGa, compared with 4% (3/78) of the +/+, +/lgGa progeny. That is, the
      complementation test suggests that Far and lgGa are alleles, whereas the mapping
      data show that they are not. We interpret the result of the Far by lgGa test as
      an example of nonallelic noncomplementation (or "false allelism") in mammals, and
      suggest that this phenomenon might be expected because open eyelids at birth
      involves a developmental threshold. Our data also show that both the embryonic
      and the maternal background genotypes strongly influence the risk of open eyelids
      in the Far by lgGa crosses. The risk to the double heterozygote (+/Far, +/lgGa)
      is highest (77%) with Far from the BALB/cGaBc rather than the ICR/Bc (0%) strain
      and in a BALB/cGaBc (77%) rather than an LGG/Bc (50%) dam in the reciprocal
      cross. This effect of genetic context on risk is also predicted by the threshold
      model. Based on our data on open eyelids at birth, we suggest that false allelism
      may be common in mammalian birth defects that result from failure to meet
      developmental thresholds, even when the "causal" mutations are Mendelian.

PMID- 9924791
TI  - Arabidopsis YAC restriction mapping.
AB  - The approach of partial restriction mapping and vector hybridisation has been
      used to restriction map and align six yeast artificial chromosomes (YACs)
      corresponding to the top arm (approximately 27.9 centiMorgans, cM) of Arabidopsis
      chromosome 5 and confirm the chimeric nature of a further four clones which map
      to this region. The restriction endonucleases Sma1 and Sfi1 which recognise rare
      medium frequency sites in the Arabidopsis genome were used. This work has
      restriction mapped a 315 kb region that includes a number of genes implicated in
      floral development, namely PISTILLATA and TOUSLED, and a number of
      uncharacterized genes involved in male gametogenesis (e.g., Ms1 and Ms37). The
      information generated can be used to transcriptionally map genes to this contig
      and will provide data for the isolation of several uncharacterized floral
      development genes which lie in this region. This approach has demonstrated how
      large tracts of YAC DNA can be mapped and aligned to show the presence/absence of
      chimeric YAC clones and provide detailed restriction knowledge for a large
      genomic region to help facilitate the positional cloning of genes.

PMID- 9924792
TI  - Inheritance of male hybrid sterility in the house musk shrew (Suncus murinus,
      Insectivora, Soricidae).
AB  - Two geographic races of the house musk shrew (Suncus murinus) were crossed and
      intercrossed in the laboratory. Many cases of male sterility were detected among
      the hybrids. Segregation analysis of the pedigree data showed that the
      inheritance of male sterility in interracial hybrids of S. murinus can be
      described within the framework of monogene polyallele model with sterility of a
      single allele combination. This model is similar if not identical to that
      proposed by Dobzhansky and Muller.

PMID- 9924793
TI  - Chromosomal structural rearrangement of Paeonia brownii and P. californica
      revealed by fluorescence in situ hybridization.
AB  - Chromosomal structural rearrangement in Paeonia brownii and P. californica (2n =
      10) was studied by in situ hybridization using 18S rDNA probes. Six major rDNA
      sites were detected in mitotic cells of P. californica; six major and two minor
      rDNA sites were found in P. brownii. Two cytotypes (A and B), with different
      chromosomal morphology and (or) rDNA locations, were observed in the population
      of P. californica. Cytotype A, with rDNA sites only on the short arms of
      chromosomes, was considered to be the normal cytotype. Both translocation and
      pericentric inversion may have occurred to give rise to cytotype B, in which one
      homolog of chromosome 4 has rDNA sites on both arms while its homolog has no rDNA
      sites: one homolog of chromosome 3 has a rDNA site on the long arm. Two
      rearranged cytotypes, C and D, were observed in the population of P. brownii.
      Given that the normal cytotype of P. brownii is most likely to have six major
      rDNA sites on the short arms of chromosomes 3, 4, and 5, and two minor sites on
      the short arms of chromosome 2, cytotype C may have resulted from a translocation
      between the short arm of one homolog of chromosome 2 and the long arm of one
      homolog of chromosome 4, and cytotype D may have resulted from a translocation
      between the short arm of one homolog of chromosome 3 and the long arm of one
      homolog of chromosome 4. These results supported previous observations, based on
      meiotic configurations, that chromosomal structural rearrangement occurred
      frequently in P. brownii and P. californica.

PMID- 9924794
TI  - Isolation and characterization of a satellite DNA family in the Saccharum
      complex.
AB  - EaCIR1, a 371-bp Erianthus-specific satellite DNA sequence, was cloned from TaqI
      restricted genomic DNA after agarose-gel electrophoresis. This sequence has 77%
      homology with a 365-bp satellite of Helictotrichon convolutum and 72% homology
      with a 353-bp tandem repeat sequence from Oryza sativa. PCR primers defined in
      the conserved regions of these repetitive sequences were used to isolate other
      satellite DNAs in different representatives of the Saccharum complex: SoCIR1 in
      Saccharum officinarum, SrCIR1 in Saccharum robustum, SsCIR1 and SsCIR2 in
      Saccharum spontaneum, and MsCIR1 in Miscanthus sinensis. EaCIR1 and SoCIR1 were
      localized to subtelomeric regions of the chromosomes by fluorescence in situ
      hybridization. Southern hybridization experiments, using two representatives of
      this repeat sequence family as probes, illustrated contrasting species
      specificity and demonstrated the existence of similar repetitive elements in
      sorghum and maize.

PMID- 9924795
TI  - A transient assay for evaluating promoters in wheat endosperm tissue.
AB  - A transient assay was developed for the evaluation of promoter sequences in wheat
      endosperm tissue. A deletion series from an omega-secalin gene promoter, located
      on chromosome 1RS.1DL of specific wheat lines, were translationally fused to a
      uidA reporter gene. These promoters were evaluated for expression in wheat
      endosperm tissue after integration of the DNA into the cell using microprojectile
      bombardment. The results were compared with those obtained using other transient
      assay systems.

PMID- 9924796
TI  - Effects of restriction endonucleases on nucleolar organizing regions in the ant
      Tapinoma nigerrimum.
AB  - The effects of some restriction endonucleases (REs) on the nucleolar organizing
      regions and on the genes for ribosomal RNA (rDNA) were analyzed using the
      nucleolar organizing region of the chromosome 6 of Tapinoma nigerrimum as an
      experimental model, since, in accordance with previous studies, the genes for
      ribosomal RNA seem to be present only in this chromosome. In situ non-digestion
      of the nucleolar organizing region was observed when EcoRI and HindIII were used.
      However, very evident digestion and partial digestion respectively were observed
      when HaeIII and Tru9I were used. Southern blot analysis realized on naked DNA
      digested with the same REs and using rDNA of Drosophila melanogaster as probe
      showed that there are target sequences for these enzymes in the rDNA. In
      accordance with the results obtained, the rDNA is poor in EcoRI and HindIII
      sequences, contains moderate amounts of Tru9I sequences and is rich in HaeIII
      sequences. All the data obtained suggest that in the nucleolar organizing region
      of Tapinoma nigerrimum, the major, if not the only, limiting factor affecting in
      situ digestion by the REs used is the presence and frequency of their specific
      restriction targets. Consequently, extraction of DNA from this chromosome region
      depends on the size of the fragments originated.

PMID- 9924797
TI  - CART, a new anorectic peptide.
AB  - Cocaine and amphetamine regulated transcript peptide (CART), is a recently
      discovered hypothalamic peptide with a potent appetite suppressing activity. In
      the rat the CART gene encodes a peptide of either 129 or 116 amino acid residues
      whereas only the short form exists in humans. The predicted signal sequence is 27
      amino acid residues resulting in a prohormone of 102 or 89 residues. The C
      terminal end of CART, consisting of 48 amino acid residues and 3 disulphide
      bonds, is thought to constitute a biologically active part of the molecule. In
      the central nervous system CART is highly expressed in many hypothalamic nuclei,
      some of which are involved in regulating feeding behaviour. The CART mRNA is
      regulated by leptin, and the expressed CART is a potent inhibitor of feeding that
      even overrides the feeding response induced by neuropeptide Y. The putative CART
      receptor is therefore a potential therapeutic target for an anti-obesity drug.

PMID- 9924798
TI  - Leptin.
AB  - Leptin is an adipocyte hormone that signals nutritional status to the central
      nervous system (CNS) and peripheral organs. Leptin is also synthetized in the
      placenta and in gastrointestinal tract, although its role in these tissues is not
      yet clear. Circulating concentrations of leptin exhibit pulsatility and circadian
      rhythmicity. The levels of plasma leptin vary directly with body mass index and
      percentage body fat, and leptin contributes to the regulation of body weight.
      Leptin plasma concentrations are also influenced by metabolic hormones, sex, and
      body energy requirements. Defects in the leptin signaling pathway result in
      obesity in animal models. Only a few obese humans have been identified with
      mutations in the leptin gene or in the leptin receptor; however, most cases of
      obesity in humans are associated with high leptin levels. Thus, in humans obesity
      may represent a state of leptin resistance. Minute-to-minute fluctuations in
      peripheral leptin concentrations influence the activity of the hypothalamic
      pituitary-ovarian and hypothalamic-pituitary-adrenal axes, indicating that leptin
      may be a modulator of reproduction, stress-related endocrine function, and
      behavior. This suggests potential roles for leptin or its antagonists in the
      diagnosis, pathophysiology and treatment of several human diseases.

PMID- 9924799
TI  - NM23-NDP kinase.
AB  - NM23 belongs to a large family of structurally and functionally conserved
      proteins consisting of 4-6 identically folded subunits of approximately 16-20
      kDa. These oligomeric proteins exhibit nucleoside diphosphate kinase (NDPK)
      activity that catalyzes nonsubstrate specific conversions of nucleoside
      diphosphates to nucleoside triphosphates. Many NM23 proteins bind DNA. In vivo,
      NM23-NDPKs regulate a diverse array of cellular events including growth and
      development. They are also implicated in the pathogenesis and metastasis of
      tumors. The mechanism whereby NM23 regulates gene expression is proposed to
      entail DNA-binding and subsequent alterations in promoter DNA structure.
      Accordingly, NM23 has the potential to become a useful reagent for gene
      manipulations.

PMID- 9924800
TI  - Properties and functions of the thiamin diphosphate dependent enzyme
      transketolase.
AB  - This review highlights recent research on the properties and functions of the
      enzyme transketolase, which requires thiamin diphosphate and a divalent metal ion
      for its activity. The transketolase-catalysed reaction is part of the pentose
      phosphate pathway, where transketolase appears to control the non-oxidative
      branch of this pathway, although the overall flux of labelled substrates remains
      controversial. Yeast transketolase is one of several thiamin diphosphate
      dependent enzymes whose three-dimensional structures have been determined.
      Together with mutational analysis these structural data have led to detailed
      understanding of thiamin diphosphate catalysed reactions. In the homodimer
      transketolase the two catalytic sites, where dihydroxyethyl groups are
      transferred from ketose donors to aldose acceptors, are formed at the interface
      between the two subunits, where the thiazole and pyrimidine rings of thiamin
      diphosphate are bound. Transketolase is ubiquitous and more than 30 full-length
      sequences are known. The encoded protein sequences contain two motifs of high
      homology; one common to all thiamin diphosphate-dependent enzymes and the other a
      unique transketolase motif. All characterised transketolases have similar kinetic
      and physical properties, but the mammalian enzymes are more selective in
      substrate utilisation than the nonmammalian representatives. Since products of
      the transketolase-catalysed reaction serve as precursors for a number of
      synthetic compounds this enzyme has been exploited for industrial applications.
      Putative mutant forms of transketolase, once believed to predispose to disease,
      have not stood up to scrutiny. However, a modification of transketolase is a
      marker for Alzheimer's disease, and transketolase activity in erythrocytes is a
      measure of thiamin nutrition. The cornea contains a particularly high
      transketolase concentration, consistent with the proposal that pentose phosphate
      pathway activity has a role in the removal of light-generated radicals.

PMID- 9924801
TI  - Inactivation and conformational changes of fatty acid synthase from chicken liver
      during unfolding by sodium dodecyl sulfate.
AB  - Fatty acid synthase is an important enzyme participating in energy metabolism in
      vivo. The inactivation and conformational changes of the multifunctional fatty
      acid synthase from chicken liver in SDS solutions have been studied. The results
      show that the denaturation of this multifunctional enzyme by SDS occurred in
      three stages. At low concentrations of SDS (less than 0.15 mM) the enzyme was
      completely inactivated with regard to the overall reaction. For each component of
      the enzyme, the loss of activity occurred at higher concentrations of SDS.
      Significant conformational changes (as indicated by the changes of the intrinsic
      fluorescence emission and the ultraviolet difference spectra) occurred at higher
      concentrations of SDS. Increasing the SDS concentration caused only slight
      changes of the CD spectra, indicating that SDS had no significant effect on the
      secondary structure of the enzyme. The results suggest that the active sites of
      the multifunctional fatty acid synthase display more conformational flexibility
      than the enzyme molecule as a whole.

PMID- 9924802
TI  - The role of glutamine, serum and energy factors in growth of enterocyte-like cell
      lines.
AB  - BACKGROUND: Glutamine is routinely added to most cell cultures. Glutamine has
      been found to be the preferential nutrient to the rapidly replicating intestinal
      mucosa, but whether this is a metabolic effect or due to other properties of this
      amino acid is not determined. To study the importance of glutamine on the growth
      of two enterocyte-like cell lines, the effects of depriving the media or
      supplementing it with glutamine were assessed in media with different serum and
      energy supplements. METHODS: CaCo-2 and HT-29 cells were grown in serum-free
      medium, with fetal bovine or synthetic serum, and with or without glucose or
      galactose. The glutamine content was varied between 0 and 4 mM. All growth assays
      were performed in triplicate by counting in a hemocytometer. RESULTS: Both cell
      lines were dependent of serum factors for growth, but displayed distinct
      requirements on glutamine supplementation. Glutamine was an obligate supplement
      with dose-dependent correlation to growth (r = 0.87, p < 0.01) for CaCo-2 cells
      cultured in synthetic, but not in fetal bovine serum. In HT-29 cells, the
      correlation between glutamine and growth was significant (r = 0.68, p < 0.05)
      only in fetal bovine serum in the absence of galactose. CONCLUSION: This study
      shows that glutamine has different growth stimulating effects on two enterocyte
      like cell lines studied. This could reflect different modes of action of
      glutamine on proliferation and differentiation in an enterocyte cell population.

PMID- 9924803
TI  - Effects of 6-aminonicotinamide on levels of soluble proteins and enzyme
      activities in various tissues of Japanese quail.
AB  - The effects of 6-aminonicotinamide (6-AN) on the levels of soluble proteins and
      enzyme activities in various tissues of Japanese quail were investigated. SDS
      polyacrylamide gel electrophoresis showed that the soluble proteins with
      molecular masses corresponding to 160.4 and 52.5 kDa were either missing or
      present at lower concentrations in the brain of the 6-AN treated group compared
      to those in the control group. The soluble liver proteins with molecular masses
      200, 120 and 70.5 kDa were missing in the treated group compared to those in the
      control while those of a molecular mass 15.1 kDa were found to be present at
      higher concentrations. Similarly, treatment with 6-AN decreased the concentration
      of soluble proteins in pectoral muscle with molecular masses 92.3, 54.5, 43.5,
      41.2, 34.5, 27.5, 20.1 and 17.5 kDa and increased those with molecular masses
      96.5, 37.7, 25.0, 19.3, 16.6, 13.8 and 10.8 kDa. In the heart, soluble proteins
      with molecular mass 84.6 kDa were increased. There was a marked reduction in the
      treatment group in the concentration of NAD in pectoral muscle but not in other
      tissues. A similar observation was also made with total RNA levels. The specific
      activity of malic enzyme was markedly increased by 6-AN treatment in the kidney
      and pectoral muscle but reduced in the liver. 6-Phosphogluconate dehydrogenase
      and lactate dehydrogenase activities were markedly reduced in the liver.
      Glyceraldehyde-3-phosphate dehydrogenase activity was significantly decreased in
      liver and pectoral muscle. NAD glycohydrolase activity was markedly decrease in
      pectoral muscle. Acetylcholinesterase activity was markedly reduced in liver but
      was enhanced in pectoral muscle. The results suggest that the metabolic actions
      of 6-AN are specific for certain proteins in the liver and muscle with the effect
      being most pronounced in muscle. The effects are also quite distinct from those
      by its analogue 3-acetylpyridine.

PMID- 9924804
TI  - Glutathione modulates lipid composition of human colon derived HT-29 cells.
AB  - Glutathione (GSH) is important in maintaining intracellular thiol status. The
      present study looked at the effect of GSH depletion on lipid composition of colon
      derived HT-29 cells. GSH was depleted in HT-29 cells by incubation either with
      buthionine-S, R-sulfoximine (BSO) or diethylmaleate (DEM). GSH was restored
      during early periods of cells growth by supplementation of growth medium with
      either GSH ester or N-acetyl cysteine (NAC). Lipids were analysed following GSH
      depletion and supplementation. Among the neutral lipids, an increase in free
      cholesterol and diacylglycerol and decrease in cholesteryl ester and
      triacylglycerol were seen in GSH-depleted cells as compared to control cells.
      There were no detectable free fatty acids either in control or GSH-depleted
      cells. Among the phospholipids, a decrease in phosphatidylcholine and
      phosphatidylinositol and an increase in phosphatidylethanolamine were observed.
      These changes were a completely reversed by supplementation of BSO-treated cells
      with GSH ester and partially reversed by N-acetyl cysteine. These results suggest
      that the GSH status of the cell plays an important role in the lipid composition
      of the cells.

PMID- 9924806
TI  - Immunochemical detection of oxidative DNA damage in cancer and aging using anti
      reactive oxygen species modified DNA monoclonal antibody.
AB  - The formation of reactive oxygen species (ROS), although a normal cellular
      activity, is considerably enhanced under chronic inflammatory conditions and
      ischemia. These species have been implicated in various disorders, mutagenesis,
      carcinogenesis and aging. Of many macromolecules, DNA is the most susceptible to
      hydroxyl radical, the most reactive of the ROS. The present study is designed to
      detect oxidative DNA damage in cancer patients and healthy aged humans using an
      anti-ROS-DNA monoclonal antibody (mAb). Purified calf thymus DNA fragments
      (approximate size 400 bp) were modified with OH, generated by UV-irradiation (254
      nm) of hydrogen peroxide. ROS-modified DNA was characterized by UV-spectroscopy,
      melting temperature, alkaline sucrose density gradient ultracentrifugation and
      ion-exchange chromatography. ROS-DNA showed single strand breaks, decrease in Tm,
      modification of thymine (58.3%) and guanine (20%). The mAb generated against ROS
      DNA was characterized for antigen binding specificity by competition ELISA.
      Monoclonal antibody showed strong binding to ROS-modified DNA, its modified
      fragments, polynucleotides and bases. With the exception of native DNA, binding
      of unmodified polynucleotides and bases was much lower. The mAb distinctly
      recognized DNA samples from lymphocytes of healthy aged humans and gave maximum
      inhibitions of 49, 53, 64 and 70%, while not reacting with DNA from young
      population. Similarly, oxidative lesions in DNA from cancer patients were also
      efficiently recognized by the mAb. DNA from healthy controls served as negative
      control. The studies demonstrate that the mAb, although cross-reactive,
      preferentially binds ROS-modified epitopes on DNA. High reactivity of mAb to DNA
      samples from cancer patients and healthy aged humans indicates increased
      oxidative stress leading to DNA damage.

PMID- 9924805
TI  - Interaction of IgG immunoglobulins with the guinea pig peritoneal macrophage Fc
      gamma receptors. Effect on the association of the receptors with the membrane
      skeleton and the cytoskeleton.
AB  - Binding of ligands to cell surface receptors may induce an interaction of the
      receptors with the cytoskeleton and/or membrane skeleton and decrease the
      solubility of the receptors in nonionic detergents. Cytochalasins, reagents
      affecting the structure of microfilaments, inhibit some cell functions induced by
      cross-linking of the receptors with ligands. Information concerning the function
      of the cytoskeleton in insolubilization of Fc gamma receptors (Fc gamma R) and in
      Fc gamma R-mediated signal transmission is rather limited. The aim of this work
      was to investigate the effect of binding of homologous (guinea pig IgG1 and IgG2)
      and heterologous (rabbit IgG) immunoglobulins to guinea pig peritoneal
      macrophages on association of the macrophage Fc gamma receptors with the membrane
      skeleton and cytoskeleton. Cross-linking the macrophage Fc gamma receptors with
      immunoglobulin ligands induced insolubilization of the receptors in nonionic
      detergents suggesting association of the receptors with the membrane skeleton and
      the cytoskeleton. The ligands showed differential effects depending on a subclass
      and origin of the IgG used. The process of association of the Fc gamma receptors
      with the skeletons was fast and did not depend on temperature. Treatment of
      insoluble complexes with cytochalasin D, DNAse I or colchicine showed that actin
      microfilaments and microtubules play a role, at least partially, in
      insolubilization of the cross-linked macrophage Fc gamma receptors. Inhibition of
      insolubilization of the macrophage Fc gamma receptors by genistein indicated that
      tyrosine kinases are involved in the process of insolubilization. The association
      with the skeletons might be a part of the process of transduction of a signal
      which depended on the subclass and origin of IgG used and on the type of the Fc
      gamma receptor.

PMID- 9924807
TI  - Porcine pyridoxal kinase c-DNA cloning, expression and confirmation of its
      primary sequence.
AB  - Porcine brain pyridoxal kinase has been cloned. A 1.2 kilo-based cDNA with a 966
      base pair open reading frame was determined from a porcine brain cortex cDNA
      library using PCR technique. The DNA sequence was shown to encode a protein of
      322 amino acid residues with a molecular mass of 35.4 kDa. The amino acid
      sequence deduced from the nucleotide sequence of the cDNA was shown to match the
      partial primary sequence of pyridoxal kinase. Expression of the cloned cDNA in E.
      coli has produced a protein which displays both pyridoxal kinase activity and
      immunoreactivity with monoclonal antibodies raised against natural enzyme from
      porcine brain. With respect to the physical properties, it is shown that the
      recombinant protein exhibits identical kinetic parameters with the pure enzyme
      from porcine brain. Although the primary sequence of porcine pyridoxal kinase has
      been shown to share 87% homology with the human enzyme, we have shown that the
      porcine enzyme carries an extra peptide of ten amino acid residues at the N
      terminal domain.

PMID- 9924808
TI  - Differential regulation of MAP kinase activity by corticotropin-releasing hormone
      in normal and neoplastic corticotropes.
AB  - Corticotropin-releasing hormone (CRH) plays an important role in regulating the
      development and function of hypothalamic-pituitary-adrenal axis. The mechanisms
      by which CRH regulates tissue-specific growth, differentiation and gene
      expression remain to be established. In the present study, we show that CRH
      differentially regulates MAP kinase activity in normal ovine anterior pituitary
      cells and mouse corticotrope AtT20 cells. Incubation of ovine normal anterior
      pituitary cells with CRH increased MAP kinase activity, an effect mimicked by
      cAMP and inhibited by the protein kinase A inhibitor H89. In contrast, incubation
      of mouse pituitary tumor AtT20 cells with CRH inhibited MAP kinase activity, an
      effect also mimicked by forskolin and inhibited by H89. This decrease in MAP
      kinase activity occurred with a time course similar to the increase seen in
      normal anterior pituitary cells. Furthermore, both effects of CRH on MAP kinase
      activity were inhibited by atrial natriuretic peptide (ANP). ANP also reversed
      the inhibition of DNA synthesis induced by CRH in AtT20 cells. Thus, CRH may
      differentially regulate cell growth in sheep normal anterior pituitary and mouse
      tumor corticotropes by modulating MAP kinase activity through a mechanism
      dependent on cAMP production and subject to regulation by ANP.

PMID- 9924810
TI  - Conversion of native oligomeric to a modified monomeric form of human C-reactive
      protein.
AB  - C-reactive protein (CRP) is a pentameric oligoprotein composed of identical 23 kD
      subunits which can be modified by urea-chelation treatment to a form resembling
      the free subunit termed modified CRP (mCRP). mCRP has distinct physicochemical,
      antigenic, and biologic activities compared to CRP. The conditions under which
      CRP is converted to mCRP, and the molecular forms in the transition, are
      important to better understand the distinct properties of mCRP and to determine
      if the subunit form can convert back to the pentameric native CRP form. This
      study characterized the antigenic and conformational changes associated with the
      interconversion of CRP and mCRP. The rate of dissociation of CRP protomers into
      individual subunits by treatment in 8 M urea-10 mM EDTA solution was rapid and
      complete in 2 min as assayed by an enzyme-linked immunofiltration assay using
      monoclonal antibodies specific to the mCRP. Attempts to reconstitute pentameric
      CRP from mCRP under renaturation conditions were unsuccessful, resulting in a
      protein retaining exclusively mCRP characteristics. Using two-dimensional urea
      gradient gel electrophoresis, partial rapid unfolding of the pentamer occurred
      above 3 M urea, a subunit dissociation at 6 M urea, and further subunit unfolding
      at 6-8 M urea concentrations. The urea gradient electrophoresis results suggest
      that there are only two predominant conformational states occurring at each urea
      transition concentration. Using the same urea gradient electrophoresis conditions
      mCRP migrated as a single molecular form at all urea concentrations showing no
      evidence for reassociation to pentameric CRP or other aggregate form. The results
      of this study show a molecular conversion for an oligomeric protein (CRP) to
      monomeric subunits (mCRP) having rapid forward transition kinetics in 8 M urea
      plus chelator with negligible reversibility.

PMID- 9924809
TI  - Presence of intestinal, liver and heart/adipocyte fatty-acid-binding protein
      types in the liver of a chimaera fish.
AB  - Five fatty-acid-binding proteins from the liver of the elephant fish
      (Callorhynchus callorhynchus), a chimaera fish that belongs--together with the
      elasmobranchs--to the ancient chondrichthyes class were isolated and
      characterized. The purification procedures for these proteins involved gel
      filtration, anion-exchange chromatography, and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis as a last step. They were submitted to "in
      gel" tryptic or cyanogen bromide digestion and the resulting peptides were
      separated by high performance liquid chromatography and then sequenced by Edman
      degradation. According to their partial amino acid sequences, one of them
      presents the highest identity with fatty-acid-binding proteins from human and
      catfish liver, another three with those from mammalian heart or adipose tissue
      and the fifth with the mammalian intestinal fatty-acid-binding protein. The
      presence of various members of this protein family, as now found in elephant fish
      and previously in catfish (Rhamdia sapo) liver, does not occur in mammalian liver
      which express only one a characteristic fatty-acid-binding protein.

PMID- 9924811
TI  - Pretesting tumors.

PMID- 9924812
TI  - Breath of fresh liquid.

PMID- 9924813
TI  - The puzzle of hypertension in African-Americans.

PMID- 9924814
TI  - How limbs develop.

PMID- 9924815
TI  - Adenylosuccinate synthetase genes: molecular cloning and phylogenetic analysis of
      a highly conserved archaeal gene.
AB  - Adenylosuccinate synthetase (PurA) catalyzes the first step in the de novo AMP
      synthesis and has been extensively studied in both Bacteria and Eukarya. We
      cloned the purA gene from the hyperthermophilic archaeon, Pyrococcus furiosus.
      The gene appears to be individually transcribed and encodes a protein of 339
      amino acids. The amino acid sequence comparison with other archael PurAs found
      from recent genome analyses indicated that two deletions, one central and the
      other C-terminal, are a common feature of archaeal PurAs. None of the 21 PurA
      homologues analyzed from Eukarya and Bacteria exhibited this feature. Amino acid
      sequences of PurAs in Archaea showed 64% average identities which were
      significantly higher than the 50% and 55% calculated for Bacteria and Eukarya,
      respectively. Several residues conserved in PurAs of both Eukarya and Bacteria
      and shown to be of catalytic importance are missing in the archaeal PurAs.
      Phylogenetic analysis using PurA as the marker grouped life into 3 domains, hence
      it was consistent with results derived from 16-18S ribosomal RNA sequences. The
      topology within the three domains, in general, portrayed the hitherto accepted
      evolutionary relationship among the organisms utilized. PurA can, thus, serve as
      an additional marker to evaluate phylogenetic inferences drawn from sequence data
      from rRNA and other conserved genes. The presence of two unique deletions in both
      euryarchaeal and crenarchaeal PurAs, but not in those of Bacteria and Eukarya, is
      a strong evidence confirming the common lineage of these two subdomains of
      Archaea.

PMID- 9924816
TI  - Characterization of the genes for the biosynthesis of the compatible solute
      ectoine in the moderately halophilic bacterium Halomonas elongata DSM 3043.
AB  - The ectoine synthesis genes of the moderately halophilic bacterium Halomonas
      elongata DSM 3043 have been precisely located in a 2.8-kb EcoRI region of a
      cosmid clone previously isolated (CANOVAS, D., VARGAS, C., IGLESIAS-GUERRA, F.,
      CSONKA, L. N., RHODES, D., VENTOSA, A., NIETO, J. J.: Isolation and
      characterization of salt-sensitive mutants of the moderate halophile Halomonas
      elongata and cloning of the ectoine synthesis genes. J. Biol. Chem. 272, 25794
      25801, 1997). This region was sequenced and three open reading frames were found
      corresponding to the genes ectA (encoding the diaminobutyric acid acetyl
      transferase), ectB (encoding the diaminobutyric acid aminotransferase) and ectC
      (encoding the ectoine synthase). These three genes were able to restore the salt
      tolerance of two H. elongata mutants defective in the synthesis of ectoine
      (strains CHR62 and CHR63). However, the H. elongata ectoine synthesis genes did
      not confer to Escherichia coli the ability to synthesize ectoine. Transposon
      insertion in the salt-sensitive mutant strain CHR63 was exactly mapped within the
      ectC gene. Moreover, sequences homologous to the H. elongata ect region have been
      found in a number of moderately halophilic bacteria belonging to the genera
      Halomonas and Chromohalobacter.

PMID- 9924817
TI  - Desulfovibrio aminophilus sp. nov., a novel amino acid degrading and sulfate
      reducing bacterium from an anaerobic dairy wastewater lagoon.
AB  - A mesophilic strain of sulfate-reducing bacterium, designated ALA-3T (T = type
      strain), was isolated from an anaerobic lagoon of a dairy wastewater treatment
      plant. The curved, Gram-negative, non-sporeforming cells (0.2 x 3.0-4.0 microns)
      existed singly or in chains, and were motile by single polar flagella. Optimum
      growth occurred at 35 degrees C and pH 7.5 on a medium containing lactate and
      sulfate. Thiosulfate or sulfite but not elemental sulfur, nitrate, or fumarate
      could also replace sulfate as an electron acceptor. Formate, alanine, aspartate,
      leucine, isoleucine, valine, and methionine, H2/CO2 and ethanol also served as
      electron donors with sulfate as an electron acceptor. Pyruvate, casamino acids,
      peptone, serine, glycine, cysteine and threonine were fermented. Sulfite and
      thiosulfate were disproportionated to sulfate and sulfide. The G + C content of
      the DNA was 66 mol % G + C. Phylogenetic analysis revealed that Desulfovibrio
      africanus was the nearest relative (similarity of 89%). Strain ALA-3T is
      physiologically and phylogenetically different from other Desulfovibrio species,
      and is designated Desulfovibrio aminophilus sp. nov. (DSM 12254).

PMID- 9924818
TI  - Phylogenetic identification of two major nitrogen-fixing bacteria associated with
      sugarcane.
AB  - Acetobacter diazotrophicus and Herbaspirillum seropedicae were identified by
      genetic methods based on 16S rRNA sequences. A specific PCR method in combination
      with probing was developed for A. diazotrophicus. The PCR system includes four
      primers, of which the primers named AC (CTGTTTCCCGCAAGGGAC) and DI
      (GCGCCCCATTGCTGGGTT) generated an 445 bp amplicon in all of the 11 A.
      diazotrophicus strains tested. The phylogenetic position of H. seropedicae was
      determined. H. seropedicae forms with Oxalobacter formigenes a separate lineage
      in the beta-subclass of Proteobacteria.

PMID- 9924819
TI  - Molecular identification of Photorhabdus luminescens strains by amplification of
      specific fragments of the 16S ribosomal DNA.
AB  - Sequence variation within the variable region of the 16S rRNA at position 440 to
      480 allowed the synthesis of specific PCR primers for the identification of
      groups within the species Photorhabdus luminescens, symbionts of entomopathogenic
      nematodes of the genus Heterorhabditis. For the second PCR primer the highly
      conserved region at 755 to 795 was used. The P. luminescens type strain specific
      primer could not recognize any other P. luminescens strain. The primer TEMPERATUS
      based on the sequence of strain DSM12190 (isolated from North West European H.
      megidis strain HSH2) identified all P. luminescens associated with H. megidis
      from North West Europe and two isolates from closely the related nematode strains
      from Ireland. The primer TROPICUS based on strain DSM12191 (isolated from the
      nematode type strain H. indica strain LN2) identified P. luminescens of tropical
      origin isolated from H. indica. Symbionts of H. bacteriophora could not yet be
      separated into well described groups with the primers used. A comparison of
      sequence data resulted in the identification of additional groups. The non
      symbiotic P. luminescens isolates are distinct in the variable region. The group
      HELIOTHIDIS contains 15 P. luminescens associated with H. bacteriophora from
      North East America. The MARELATUS group contains symbionts of the nematode H.
      marelatus from the West Coast of the US. The data together with the specific
      symbiotic association of P. luminescens strains with different nematode species
      support the division of the taxon P. luminescens into different species.

PMID- 9924820
TI  - Contribution to phenotypic and genotypic characterization of Bacillus
      licheniformis and description of new genomovars.
AB  - A study of phenotypic and genotypic characteristics was carried out on 182
      strains isolated from soil of different geographical areas; the type strains were
      B. licheniformis, B. subtilis, B. pumilus, B. cereus and B. coagulans. The
      results showed, primarily on the basis of phenotypic features, that all the
      isolates belonged to the B. licheniformis species, however DNA relatedness
      studies revealed only 161 to be genetically related to B. licheniformis, the DNA
      relatedness levels ranging from 66 to 100%. The other 21 isolates appeared to be
      genetically distinct not only from B. licheniformis but also from B. subtilis and
      B. pumilus, where there were low levels of DNA relatedness (from 4 to 37%).
      Nevertheless the ARDRA results indicate that the 21 atypical isolates were
      phylogenetically related to B. licheniformis. Our data and the phenotypic
      homogeneity found suggest the presence of three different genomovars.

PMID- 9924821
TI  - Molecular diversity and relationship within Lactococcus lactis, as revealed by
      randomly amplified polymorphic DNA (RAPD).
AB  - Lactococcus lactis strains are widely used in industrial dairy fermentations.
      Conventional phenotypic tests have been used for years to classify members of
      this species into two subspecies, lactis and cremoris, and play a key role in the
      choice of strains to be used in particular cheese fermentations. DNA
      hybridisation techniques have also been used for strain classification, giving
      rise to two genome homology groups. However, results showed discrepancies between
      the two methods of classification. We applied the randomly amplified polymorphic
      DNA fingerprinting (RAPD) technique to resolve previous contradictions in
      lactococcal classifications. Unlike usual RAPD methods, we use three primers to
      classify 113 strains and integrate the resulting information by a digitised
      programme used for this purpose. Our analysis revealed three major RAPD groups,
      designated G1, G2 and G3. G1 and G3 contain strains of the lactis subspecies, and
      G2 contains strains of the cremoris subspecies, as previously defined by
      phenotypic characteristics. Moreover, group G1 corresponds to one genome homology
      group, and groups G2 and G3 correspond to the second one. The taxonomic structure
      within L. lactis is therefore unusual: two distinct genetic groups of strains
      show indistinguishable phenotypes, while conversely, two phenotypically distinct
      groups are genetically homologous. We hypothesize that a subfamily of the subsp.
      lactis group gave rise to the cremoris subspecies.

PMID- 9924822
TI  - Analysis of LMW RNA profiles of Frankia strains by staircase electrophoresis.
AB  - An optimized technique of polyacrylamide gel electrophoresis, Staircase
      Electrophoresis (SCE), was applied to determine the stable Low Molecular Weight
      RNA (LMW RNA) profiles of 25 Frankia strains from diverse geographic origins and
      host specificity groups as well as species from other actinomycete genera.
      Application of the technique permits the rapid identification of Frankia strains
      and their differentiation from other actinomycetes. The isolates used in this
      study were grouped in eight clusters, each comprising strains with identical LMW
      RNA profiles. Comparison of these results with others obtained from DNA sequences
      or DNA hybridization methods suggest a high degree of complexity in the genus
      Frankia. Application of SCE to profile LMW RNA should in the future facilitate
      biodiversity studies of Frankia and discrimination of new species.

PMID- 9924823
TI  - Nearly identical 16S rRNA sequences recovered from lakes in North America and
      Europe indicate the existence of clades of globally distributed freshwater
      bacteria.
AB  - We compared bacterial 16S ribosomal RNA gene sequences recovered from Lake
      Loosdrecht, the Netherlands, to reported sequences from lakes in Alaska and New
      York State. In each of the three lake systems, which differ in pH and trophic
      state, some sequence types were found without related sequences (sequence
      identity < 90%) in the data sets from the other two systems. Two sequences in the
      Actinomycetes and Verrucomicrobia radiations were more closely related to
      sequences from the New York lakes data set than to any other sequence in the
      global databases. However, the most striking similarities were found in the
      subdivisions alpha and beta of the Proteobacteria. In these subdivisions three
      different clusters of highly related bacteria were identified (97-100% sequence
      identity) that were represented in all three lake regions. The clusters contained
      no members other than freshwater bacteria. One cluster falls within a
      monophyletic aquatic supergroup that apparently diverged early in evolution into
      an exclusive freshwater cluster and an exclusive marine cluster, the so-called
      SAR11 cluster. The detection of these three bacterial clades in lakes
      distinguished by geographic distance as well as physical and chemical diversity
      suggests that these organisms are dispersed globally and that they possess unique
      functional capabilities enabling successful competition in a wide range of
      freshwater environments.

PMID- 9924824
TI  - Phylogenetic and physiological diversity of sulphate-reducing bacteria isolated
      from a salt marsh sediment.
AB  - The phylogenetic and physiological diversity of sulphate-reducing bacteria
      inhabiting a salt marsh rhizosphere were investigated. Sulphate-reducing bacteria
      were isolated from a salt marsh rhizosphere using enrichment cultures with
      electron donors thought to be prevalent in the rhizosphere of Spartina
      alterniflora. The relationship between phylogeny and nutritional characteristics
      of 10 strains was investigated. None of the isolates had 16S rRNA sequences
      identical to other delta subclass sulphate-reducers, sharing 85.3 to 98.1%
      sequence similarity with 16S rRNA sequences of their respective closest
      relatives. Phylogenetic analysis placed two isolates, obtained with ethanol as an
      electron donor, within the Desulfovibrionaceae. Seven isolates, obtained with
      acetate, butyrate, propionate, or benzoate, were placed within the
      Desulfobacteriaceae. One isolate, obtained with butyrate, fell within the
      Desulfobulbus assemblage, which is currently considered part of the
      Desulfobacteriaceae family. However, due to the phylogenetic breadth and
      physiological traits of this group, we propose that it be considered a new
      family, the "Desulfobulbusaceae." The isolates utilised an array of electron
      donors similar to their closest relatives with a few exceptions. As a whole, the
      phylogenetic and physiological data indicate isolation of several sulphate
      reducing bacteria which might be considered as new species and representative of
      new genera. Comparison of the Desulfobacteriaceae isolates' 16S rRNA sequences to
      environmental clones originating from the same study site revealed that none
      shared more than 86% sequence similarity. The results provide further insight
      into the diversity of sulphate-reducing bacteria inhabiting the salt marsh
      ecosystem, as well as supporting general trends in the phylogenetic coherence of
      physiological traits of delta Proteobacteria sulphate reducers.

PMID- 9924825
TI  - Sulfur oxidation in rice field soil: activity, enumeration, isolation and
      characterization of thiosulfate-oxidizing bacteria.
AB  - In rice paddy fields the bulk soil is anoxic, but oxygenated zones occur in the
      surrounding of the rice roots to where oxygen is transported via the aerenchyma
      system of the rice plants. In the anaerobic soil compartments sulfate is consumed
      by sulfate-reducing bacteria. In the rhizosphere the reduced sulfur compounds can
      be reoxidized by sulfur-oxidizing bacteria. Measurements of the potential
      activity of thiosulfate-oxidizing bacteria in soil slurries derived from planted
      rice soil microcosms showed turnover rates of 2-6 mumol d-1 g-dw-1. Thiosulfate
      was oxidized to sulfate with tetrathionate as intermediate. Most probable number
      (MPN) enumeration with three aerobic media and one anaerobic nitrate-amended
      medium showed that thiosulfate-oxidizing bacteria were abundant in paddy soil and
      in rhizosphere soil at numbers of 10(5) to 10(6) per gram dry weight soil. Nine
      isolates of S-oxidizing bacteria were obtained from enrichment cultures or from
      the highest dilutions of the MPN series and were affiliated to four different
      phylogenetic groups. These isolates were characterized by physiological
      properties and by comparative 16S rDNA sequence analysis. Three isolates (TA1
      AE1, TA1-A1 and TA12-21) were shown to be facultatively chemolithoautotrophic
      strains of Ancylobacter aquaticus. Three further isolates (Tv6-2b, Z2A-6A and Z4A
      2A) were also facultatively chemolithoautotrophic and were affiliated with the
      Xanthobacter sp. group, probably representing new strains of X. flavus or X.
      tagetidis. Strain SZ-2111 was phylogenetically related to Bosea thiooxidans.
      However, the genus Bosea is described as obligately heterotrophic, whereas strain
      5Z-2111 was able to grow autotrophically. The isolates 5Z-C1 and TBW3 were
      obligate chemolithoautotrophs and were closely affiliated with Thiobacillus
      thioparus. Our results showed that S-oxidizing bacteria were abundant and active
      in rice paddy soil and consisted of physiologically and phylogenetically diverse
      populations.

PMID- 9924826
TI  - Analysis of broad-scale differences in microbial community composition of two
      pristine forest soils.
AB  - Broad-scale differences in soil microbial community composition were analyzed in
      two contrasting soils using DNA reassociation and % G + C profiles for analysis
      on the community-level, and filter- and whole cell hybridization techniques for a
      coarse-level characterization of larger phylogenetic groups of bacteria.
      Reassociation analysis of DNA from bacterial fractions extracted from the organic
      soil Seim and the mineral soil Hau revealed similar complexity of the communities
      with 5700 and 4900 different bacterial genomes (g soil [dry wt])-1, respectively.
      Thermal denaturation studies showed wide % G + C distributions in DNA from
      bacteria of both soils. Differences in the median % G + C with 55 to 61% for the
      bacterial community in soil Seim and 61 to 66% for that in soil Hau indicated a
      higher proportion of bacteria with a high DNA G + C content in soil Hau. In situ
      hybridization with fluorescent (Cy3-labeled) probes targeting larger phylogenetic
      groups showed minor differences between both soils, and between direct detection
      of bacteria in dispersed soil slurries and in bacterial fractions extracted from
      soils through about 90% of the total bacteria were lost during extraction. In
      dispersed slurries of both soils, only probes ALF1b, SRB385, and PLA46 hybridized
      to cells accounting for more than 1% of the DAPI-stained cells, while numbers
      obtained after hybridization with probes ARCH915, BET42a, GAM42a, HGC69a, and
      CF319a were below the detection limit set at < 1%. These results were confirmed
      by in situ hybridization with horseradish peroxidase (HRP)-labeled probes and
      subsequent Cy3-tyramide signal amplification. In contrast, dot blot hybridization
      with probe HGC69a indicated significant amounts of Gram-positive bacteria with a
      high DNA G + C content in both soils. These could subsequently be visualized in
      non-dispersed soil slurries by in situ hybridization with HRP-labeled probe
      HGC69a and Cy3-tyramide signal amplification. Filamentous Gram-positive bacteria
      with a high DNA G + C content, likely actinomycetes, which are present in soil
      Hau in significant numbers are obviously destroyed by procedures used for soil
      dispersion.

PMID- 9924827
TI  - Diversity of lactic acid bacteria associated with ducks.
AB  - The diversity of lactic acid bacteria occurring in the crop and intestinal
      content of ducks of different ages (5 to 34 days) was evaluated using the RAPD
      PCR technique and comparative sequence analysis of 16S rRNA. Cluster analysis
      derived from isolates grown on Rogosa agar used for the enrichment of lactic acid
      bacteria, revealed at least twenty six different groups of organisms representing
      species, subspecies and strains belonging to Streptococcus, Enterococcus,
      Pediococcus, Weissella and Lactobacillus. Homofermentative and heterofermentative
      lactobacilli were identified, belonging to the phylogenetically defined Lb.
      acidophilus, Lb. salivarius and Lb. reuteri groups.

PMID- 9924829
TI  - Can geriatric psychiatry services make a difference?

PMID- 9924828
TI  - Group specific PCR-detection of potential trichothecene-producing Fusarium
      species in pure cultures and cereal samples.
AB  - A PCR based assay (Tox5 PCR) which analyses Fusarium species potentially
      producing trichothecenes was developed using a pair of primers derived from the
      DNA-sequence of the trichodiene synthase gene (tri5). The primer pair was tested
      using DNA isolated from a variety of strains representing 64 species and
      varieties of Fusarium as well as from other fungi, bacteria and cereals. A 658 bp
      PCR fragment was specifically amplified with DNA isolated from strains of species
      belonging to the Fusarium sections Discolor, Sporotrichiella, Arthrosporiella,
      Gibbosum, and "Dlaminia". PCR products obtained were sequenced. Alignment to tri5
      sequences given in the literature revealed a high degree of homology. Results of
      the PCR developed correlated well with literature data on the trichothecene
      producing capabilities of the respective species. Potential trichothecene
      producing fusaria were detected in contaminated cereals and malts using the Tox5
      PCR assay. Intensity of the signals produced were well correlated with the
      concentration of deoxynivalenol (DON) in samples of wheat.

PMID- 9924830
TI  - Practice of geriatric psychiatry and mental health services for the elderly:
      results of an international survey.
AB  - The authors conducted a survey of members of the International Psychogeriatric
      Association (IPA) to determine the state of development of both the profession of
      geriatric psychiatry and services for mentally ill elderly. Ratings for both
      issues were based on a scale of 1 to 4, with 1 being little to no development and
      4 being the highest. A rating of 2 was set as the desired minimum, and 12
      countries met this goal in both categories, with 6 more countries reaching this
      goal in service development only. We conclude that although the field of
      geriatric psychiatry and services for mentally ill elderly are still
      underdeveloped in much of the world, in many countries they are developed
      sufficiently enough that the IPA is in an excellent position to provide both
      information and technical assistance to nations wishing to advance.

PMID- 9924831
TI  - Postsecondary education and dementia risk in older Jesuit priests.
AB  - Lack of early childhood education has been implicated as a risk factor for
      dementia in late life. It is unclear whether dementia risk is also associated
      with less education in the adult years. The purpose of the present study was to
      determine whether amount of postsecondary education (i.e., education beyond the
      high school or 12th-grade level) is associated with dementia after age 60.
      Cognitive function (assessed by a neuropsychological test battery) and the
      prevalence of dementia (assessed by clinical criteria) were determined in 86
      Jesuit priests (age 60 to 98) who had from 0 to 23 years of postsecondary
      education. Logistic regression was used to estimate the odds of dementia as a
      function of postsecondary education. The risk of dementia was increased in those
      with less postsecondary education (odds ratio = 3.4; 95% confidence interval, 1.2
      to 10.0) after adjustment for age, IQ, and depression. These findings support an
      association between amount of postsecondary education and risk of dementia in
      late life.

PMID- 9924832
TI  - Premorbid personality traits in Alzheimer's disease: do they predispose to
      noncognitive behavioral symptoms?
AB  - The purpose of this study was to examine whether premorbid personality traits
      predispose to noncognitive symptoms in Alzheimer's disease (AD). The Munich
      Personality Test was used to evaluate caregivers' perception of personality prior
      to symptom onset in 56 outpatients with probable AD. Caregivers also completed
      the "mood" and "disturbed behavior" scales of the Nurses' Observation Scale for
      Geriatric Patients. A neuropsychiatrist rated depressive symptoms on the Cornell
      Scale for Depression and the occurrence of personality change in four domains
      according to ICD-10. Under statistical control of confounding variables, results
      showed a moderate association between (high) premorbid neuroticism, subsequent
      troublesome behavior, and personality change, on the one hand, and (low)
      frustration tolerance and depression, on the other. Premorbid personality traits
      may indeed predispose to subsequent noncognitive symptoms in AD.

PMID- 9924833
TI  - A stimulation-retreat special care unit for elders with dementing illness.
AB  - Two equivalent special care nursing home units for elders with dementing illness
      were randomly designated as experimental and control units for an intervention
      called the "stimulation-retreat" model. This model introduced a set of staffing
      and program changes whose purpose was to diagnose, prescribe, and apply a package
      of care according to individual needs for additional stimulation or relief from
      stimulation ("retreat"). A total of 49 experimental and 48 control unit residents
      completed 12 months of care and were evaluated at baseline, 6 months, and 12
      months. It was hypothesized that the intervention would not affect the basic
      disability (cognitive and activities of daily living functions), would improve
      negative behaviors and observed affects, and would have maximum impact in
      increasing positive behaviors and affects. Over time, most functions worsened,
      including negative attributes and affects. Lesser decline in positive affect and
      increases in external engagement, however, led to the conclusion that the
      intervention showed a marginally significant and selective effect on positive
      behaviors and affect.

PMID- 9924834
TI  - Behavioral approaches for reducing agitation in residents of long-term-care
      facilities: critical review and suggestions for future research.
AB  - Many residents in long-term-care facilities demonstrate agitated behaviors.
      Research on behavioral approaches for reducing agitation in nursing home
      residents has been conducted during the past 25 years. This research is
      critically reviewed in this article and suggestions for future research are
      offered. Empirical evidence suggests that behavioral approaches are effective.
      Antecedent control strategies have been shown to reduce physically nonaggressive
      behaviors. Both aggressive and verbally agitated behaviors have been successfully
      treated by manipulating reinforcing consequences of these behaviors. Future
      research in this area needs to test behavioral treatments using randomized group
      designs, compare behavioral interventions to other treatments used alone or in
      combination, specify criteria for clinically significant improvement, diversify
      and ascertain the validity of assessment methods, and verify the maintenance of
      treatment effects over relatively long follow-up periods.

PMID- 9924835
TI  - Reliability and validity of a new measure of severity of delirium.
AB  - The objective of this study was to assess the psychometric properties of a new
      instrument, the Delirium Index (DI), to measure changes in the severity of the
      symptoms of delirium among patients previously diagnosed with delirium. Subjects
      were medical inpatients aged 65 and over diagnosed with delirium by the Confusion
      Assessment Method. Interrater reliability of the DI was .78 between research
      assistants (concordance coefficient) and was .88 between research assistants and
      geriatric psychiatrists. Criterion validity, assessed by the correlation between
      DI and Delirium Rating Scale scores (Spearman's correlation coefficient, r), was
      .84. Construct validity was assessed using correlations of the DI with two
      measures of current function for convergent validity (r = -.60, -.70) and two
      measures of function before admission for discriminant validity (r = .26,-.42).
      We conclude that the DI has acceptable levels of interrater reliability,
      criterion validity, and construct validity.

PMID- 9924836
TI  - When others decide: reasons for allowing patients with Alzheimer's disease to
      participate in nontherapeutic research.
AB  - The quality of information given to family members of patients with Alzheimer's
      disease was studied. The patients had participated in a pharmacological
      investigation. The relatives were generally satisfied with the information given,
      and perceived it as adequate. The reasons given for allowing the patients to
      participate in the investigation were mainly altruistic.

PMID- 9924837
TI  - Hallucinogens at the turn of the century: an introduction.

PMID- 9924838
TI  - Psychoactive plants and ethnopsychiatric medicines of the Matsigenka.
AB  - For the Matsigenka of the Peruvian Amazon, health and well-being in daily life
      depend upon harmonious relationships within the social group and with the spirit
      world. Psychoactive plants play a crucial role in curing disrupted social
      relationships while giving humans access to the otherwise remote, parallel world
      of spirits. Different species and cultivars of psychoactive plants, as well as
      varying admixtures and doses, are used to obtain different intensities and
      qualities of psychoactive experience, depending upon the individual's goals.
      Strongly psychoactive plants are used by shamans to travel to the realm of
      spirits. A number of mild to strongly psychoactive plants are used by male
      hunters to purify their souls and improve their aim. Mildly psychoactive plants
      are used to improve women's concentration for spinning and weaving cotton, to
      control negative emotions such as grief and anger, to manipulate the content of
      dreams, and to pacify sick or frightened children. A majority of such remedies
      come from the botanical families of Rubiaceae, Solanaceae and Cyperaceae, known
      sources of psychoactive compounds. Interdisciplinary research into the culture,
      botany and pharmacology of psychoactive plants in indigenous medical systems
      contributes to a better understanding of the role of psychological states in
      human health and well-being.

PMID- 9924839
TI  - Hallucinogenic drugs and plants in psychotherapy and shamanism.
AB  - Western psychotherapy and indigenous shamanic healing systems have both used
      psychoactive drugs or plants for healing and obtaining knowledge (called
      "diagnosis" or "divination" respectively). While there are superficial
      similarities between psychedelic-assisted psychotherapy and shamanic healing with
      hallucinogenic plants, there are profound differences in the underlying worldview
      and conceptions of reality. Four paradigms are reviewed: (1) psychedelic
      psychotherapy within the standard Western paradigm--here the drug is used to
      amplify and intensify the processes of internal self-analysis and self
      understanding; (2) shamanic rituals of healing and divination, which involve
      primarily the shaman or healer taking the medicine in order to be able to "see"
      the causes of illness and know what kind of remedy to apply; (3) syncretic folk
      religious ceremonies, in which the focus seems to be a kind of community bonding
      and celebratory worship; and (4) the "hybrid shamanic therapeutic rituals," which
      incorporate some features of the first two traditions. There are two points in
      which the worldview of the shamanic and hybrid shamanic ceremonies differs
      radically from the accepted Western worldview: (1) the belief and assumption
      (really, perception) that there are multiple realities ("worlds") that can be
      explored in expanded states of consciousness; and (2) the belief that "spirits,"
      the beings one encounters in dreams and visions, are just as real as the physical
      organism.

PMID- 9924840
TI  - Human nature and the nature of reality: conceptual challenges from consciousness
      research.
AB  - Holotropic states (a large special subgroup of nonordinary states of
      consciousness) have been the focus of many fields of modern research, such as
      experiential psychotherapy, clinical and laboratory work with psychedelic
      substances, field anthropology, thanatology, and therapy with individuals
      undergoing psychospiritual crises ("spiritual emergencies"). This research has
      generated a plethora of extraordinary observations that have undermined some of
      the most fundamental assumptions of modern psychiatry, psychology, and
      psychotherapy. Some of these new findings seriously challenge the most basic
      philosophical tenets of Western science concerning the relationship between
      matter, life, and consciousness. This article summarizes the most important major
      revisions that would have to be made in our understanding of consciousness and of
      the human psyche in health and disease to accommodate these conceptual
      challenges. These areas of changes include: a new understanding and cartography
      of the human psyche; the nature and architecture of emotional and psychosomatic
      disorders; therapeutic mechanisms and the process of healing; the strategy of
      psychotherapy and self-exploration; the role of spirituality in human life; and
      the nature of reality.

PMID- 9924841
TI  - Hallucinogens, serotonin and obsessive-compulsive disorder.
AB  - The serotonin (5-HT) neurotransmitter system has been implicated in the
      pathophysiology of several neuropsychiatric disorders, especially obsessive
      compulsive disorder (OCD). Blockade of 5-HT reuptake appears to be an important
      initial neurobiological event in the therapeutic mechanism of action of
      antiobsessional drugs. However, for reasons that continue to be poorly
      understood, clinical improvement following initiation of treatment with 5-HT
      reuptake inhibitors can take up to eight to 12 weeks, and most patients do not
      fully improve. Recent data suggest that activation of 5-HT2A and/or 5-HT2C
      receptors may be important for the improvement of OCD symptoms. Most psychedelic
      drugs are potent agonists at 5-HT2A and 5-HT2C receptors and their binding
      potency to these receptors is strongly correlated with their human potency as
      hallucinogens. This article will briefly review the relevant clinical and
      preclinical studies relating to the effects of hallucinogens on OCD. These data
      suggest that activation of 5-HT2 receptors by hallucinogens may lead to acute
      reduction of, as well as possible longer-lasting beneficial effects on, the
      symptoms of OCD. Evidence for and against involvement of 5-HT2A and/or 5-HT2C
      receptors in the therapeutic effects of drug therapies for OCD are reviewed.
      Issues related to the pharmacological properties and safety of psychedelic drugs,
      when considered as potential treatments for patients with OCD, are summarized.
      The authors suggest that controlled trials of potent 5-HT2 agonists in people
      suffering from OCD are warranted.

PMID- 9924842
TI  - Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination
      for severe adverse interactions.
AB  - The Amazonian psychoactive plant beverage ayahuasca has attracted increasing
      interest in recent years. Little attention has been given, however, to
      potentially dangerous interactions with other drugs. In particular, the
      interaction between the potent monoamine oxidase-inhibiting harmala alkaloids in
      ayahuasca and the selective serotonin reuptake inhibitor (SSRI) class of
      antidepressants may induce a serotonin syndrome with potentially grave outcome.
      Caution is advised when combining ayahuasca with certain pharmaceutical drugs.

PMID- 9924843
TI  - A method of conducting therapeutic sessions with MDMA.
AB  - A method for preparing clients and conducting therapeutic sessions with 3,4
      methylenedioxymethamphetamine (MDMA) is described, with emphasis on the need for
      careful attention to the mental set of therapists and clients and the setting of
      the session. The therapists' belief was that MDMA inhibited the fear response to
      a perceived emotional threat, allowing the client to place the emotional sequelae
      of past experiences into a more realistic perspective in their current emotional
      lives and relationships. Clients were carefully screened and prepared until they
      had a clear purpose for the session, including a willingness to experience and to
      learn from anything that might happen. Sympathomimetic effects of MDMA determined
      the medical contraindications, and clients with histories of serious functional
      psychiatric impairments were excluded. Total doses of 75-150 mg, plus 50 mg if
      requested later, were administered, followed by clients lying down and listening
      to music with eyeshades and headphones during the peak MDMA effect. Screening and
      follow-up questionnaires were utilized. Two case histories are presented: a man
      achieving relief of pain from multiple myeloma, and a woman finding relief from
      problems as the daughter of Holocaust survivors. Use of consciousness-altering
      drugs in other contexts is discussed.

PMID- 9924844
TI  - Treatment of alcoholism using psychedelic drugs: a review of the program of
      research.
AB  - Following Albert Hofmann's discovery of LSD's psychoactive properties in 1943,
      and previous to their scheduling as controlled substances, the psychedelic drugs
      were widely studied--six international conferences and hundreds of papers
      discussed their potential therapeutic usefulness. The observation that the
      frightening experience of delirium tremens sometimes led alcoholics to moderate
      their alcohol intake suggested to early psychedelic researchers that the
      "psychotomimetic" experience thought to be produced by LSD could be used to treat
      alcoholism. A number of hypothesis-generating studies employing a variety of
      research designs to examine this premise were completed, but relatively few
      controlled trials attempted hypothesis testing. After twenty-five years of study,
      a combination of flawed methodology, uneven results and social reprehension led
      to the abandonment of research on the therapeutic use of psychedelic drugs,
      leaving many avenues of inquiry unexplored and many questions unanswered. Today,
      after a thirty-year hiatus, this research is gradually being resumed, and there
      is renewed interest in the findings of previous studies. This article explores
      the history of one branch of psychedelic research, the therapeutic use of LSD in
      the treatment of alcoholism, and of the events that led to the relabeling of the
      "hallucinogens" as drugs of abuse.

PMID- 9924845
TI  - Dr. Leary's Concord Prison Experiment: a 34-year follow-up study.
AB  - This study is a long-term follow-up to the Concord Prison Experiment, one of the
      best-known studies in the psychedelic psychotherapy literature. The Concord
      Prison Experiment was conducted from 1961 to 1963 by a team of researchers at
      Harvard University under the direction of Timothy Leary. The original study
      involved the administration of psilocybin-assisted group psychotherapy to 32
      prisoners in an effort to reduce recidivism rates. This follow-up study involved
      a search through the state and federal criminal justice system records of 21 of
      the original 32 subjects, as well as personal interviews with two of the subjects
      and three of the researchers: Timothy Leary, Ralph Metzner and Gunther Weil. The
      results of the follow-up study indicate that published claims of a treatment
      effect were erroneous. This follow-up study supports the emphasis in the original
      reports on the necessity of embedding psilocybin-assisted psychotherapy with
      inmates within a comprehensive treatment plan that includes post-release, nondrug
      group support programs. Despite substantial efforts by the experimental team to
      provide post-release support, these services were not made sufficiently available
      to the subjects in this study. Whether a new program of psilocybin-assisted group
      psychotherapy and post-release programs would significantly reduce recidivism
      rates is an empirical question that deserves to be addressed within the context
      of a new experiment.

PMID- 9924847
TI  - Cardiac transgenic and gene-targeted mice as models of cardiac hypertrophy and
      failure: a problem of (new) riches.

PMID- 9924846
TI  - Reflections on the Concord Prison project and the follow-up study.

PMID- 9924848
TI  - Nitrate therapy is an alternative to furosemide/morphine therapy in the
      management of acute cardiogenic pulmonary edema.
AB  - BACKGROUND: Nitrates are superior to furosemide in the management of acute
      pulmonary edema associated with myocardial infarction; however, their role in the
      absence of infarction is unclear. METHODS AND RESULTS: A randomized comparison
      was undertaken of the relative effectiveness of primary therapy with either
      intravenous morphine/furosemide (men/women; n = 32) or nitroglycerin/N
      acetylcysteine (NTG/NAC; n = 37) in consecutive patients with acute pulmonary
      edema. The primary end point was change in PaO2/FIO2 over the first 60 minutes of
      therapy. Secondary end points were needed for mechanical respiratory assistance
      (ie, continuous positive airway pressure via mask or intubation and ventilation)
      and changes in other gas exchange parameters. Both treatment groups showed
      improvement in oxygenation after 60 minutes of therapy; however, this reached
      statistical significance only with NTG/NAC therapy. There was no significant
      difference between groups in the assessed parameters (95% CI for differences in
      Pao2/FIO2: furosemide/morphine -12 to 23 and NTG/NAC 4 to 44), a finding also
      confirmed in 32 patients presenting with respiratory failure. Only 11% of the
      study group required mechanical ventilatory assistance (continuous positive
      airway pressure in 4 patients and intubation and ventilation in 3 patients).
      CONCLUSIONS: NTG/NAC therapy is as effective as furosemide/morphine in the
      initial management of acute pulmonary edema, regardless of the presence or
      absence of respiratory failure. The necessity for mechanical ventilatory
      assistance is infrequent in these patients, regardless of the initial medical
      treatment regimen.

PMID- 9924849
TI  - Efficacy and safety of carvedilol in patients with chronic heart failure
      receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure
      Research Collaborative Group.
AB  - BACKGROUND: The beta-blocker/vasodilator carvedilol is found to have beneficial
      effects in patients with chronic heart failure. However, the safety and efficacy
      of this agent in the presence of concomitant amiodarone therapy has not been
      previously determined. METHODS AND RESULTS: We retrospectively analyzed the
      Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study
      of 415 patients with mild to moderate ischemic heart failure where amiodarone was
      administered as part of the treatment therapy (in 52 patients). After the open
      label carvedilol run-in, patients received carvedilol (target dose 25 mg twice
      daily) or placebo for an average of 19 months. The main adverse events during
      this double-blind period were worsened heart failure, hypotension/dizziness,
      bradycardia/atrioventricular block, and aggravation of angina. By Chi square
      analysis, carvedilol and amiodarone together were not associated with a greater
      overall incidence of adverse effects than either drug alone. The beneficial
      effects of carvedilol on left ventricular ejection that were observed in the main
      trial were preserved in the presence of amiodarone. CONCLUSIONS: Carvedilol is a
      useful additional therapy for patients with chronic heart failure already
      receiving amiodarone. Carvedilol can be added to amiodarone in these patients
      without expectation of increased adverse effects or loss of clinical efficacy.

PMID- 9924850
TI  - Beta-blockade and amiodarone therapy: twin brothers from different parents.

PMID- 9924851
TI  - The relationship between cardiac function and neuropsychological status among
      heart transplant candidates.
AB  - BACKGROUND: Cognitive deficits among heart transplant candidates have been well
      documented. This study was designed to examine the hypothesis that impaired
      cognitive test performance among heart transplant candidates may be attributed,
      in part, to decreased cerebral perfusion secondary to poor cardiac function.
      METHODS AND RESULTS: Sixty-two patients participated in the study who underwent
      heart catheterization within 1 day of completing a battery of cognitive tests.
      Multiple demographic and patient characteristics were examined for their
      potential moderating role in the relationship between measures of cardiac
      function and cognitive performance including age, education, race, gender,
      psychiatric history, medication usage, cardiac surgical history, and self
      reported symptoms of depression and anxiety. Only age and education were
      significantly related to cognitive performance (P < .01). Thus, partial
      correlation analyses controlling for age and education were used to examine the
      relationship between cardiac function and cognitive performance. In general,
      increasing hemodynamic pressure variables (ie, pulmonary artery pressure and
      right atrial pressure), and to a lesser extent cardiac output and cardiac index,
      were related (r = - .32 to - .43; P < .01) to decreased performance on cognitive
      tasks that assessed simple attention, speed of mental processing, and mental
      flexibility (Digit Span-Forward, Trail Making Test-Part B, Symbol Digits
      Modalities Test, and Stroop Neuropsychological Screening Test). Left ventricular
      ejection fraction, systemic and pulmonary vascular resistance, and mean arterial
      pressure were largely unrelated to cognitive performance in this sample of
      patients with end stage cardiac disease. CONCLUSIONS: Hemodynamic pressure
      variables seem to be most consistently related (ie, inversely) to cognitive
      functioning among heart transplant candidates.

PMID- 9924852
TI  - Regulation of regional norepinephrine spillover in heart failure: the effect of
      angiotensin II and beta-adrenergic agonists in the forearm circulation.
AB  - BACKGROUND: Prejunctional receptors for angiotensin II (A-II) and norepinephrine
      (NE) have been reported to facilitate NE release. If operative in patients with
      congestive heart failure (CHF), such receptors could participate in positive
      feedback cycles amplifying sympathoactivation. METHODS AND RESULTS: A-II and
      isoproterenol (ISO) would increase regional NE spillover via facilitation of
      presynaptic release of NE in the forearm circulation of patients with chronic
      stable CHF. A-II, ISO, and nitroprusside (NP) were sequentially infused into the
      brachial arteries of 10 patients with chronic stable CHF, which was attributed to
      dilated cardiomyopathy. Forearm blood flow (FBF) was measured via plethysmography
      and regional spillover of NE was measured by using the isotope dilution method of
      Esler. A-II (5 ng/min) produced a nonsignificant decline in FBF (1.87+/-0.14 to
      1.46+/-0.1 mL/100 g/min, P = .07) and did not change regional NE spillover (418+/
      128 to 409+/-121 ng/min). ISO increased FBF from 1.6+/-0.12 to 4.3+/-0.7 mg/100
      g/min (P < .001). Regional NE spillover increased from 337+/-86 to 856+/-300
      ng/min (P < .001). Venous NE and regional extraction of NE did not change. NP
      increased FBF from 2.0+/-0.3 to 6.3+/-1.2 mL/100 g/min (P < .001; P = NS v change
      with ISO) and also increased regional NE spillover (301+/-99 to 712+/-288 ng/min,
      P < .001; P = NS v change with ISO). As with ISO, venous NE and extraction of NE
      were not altered. CONCLUSIONS: Mild vasoconstrictor infusions of A-II do not
      increase regional NE spillover in the forearm circulation of patients with CHF.
      The beta-adrenergic agonist ISO does increase regional spillover, but the effect
      seems to be primarily related to flow rather than presynaptic stimulation of NE
      release. These data argue against an important positive feedback loop involving A
      II and NE on sympathoactivation, at least with the dosages of the agonists
      studied and in the limb circulation in chronic stable CHF.

PMID- 9924853
TI  - AT1 angiotensin II receptor inhibition in pacing-induced heart failure: effects
      on left ventricular performance and regional blood flow patterns.
AB  - BACKGROUND: AT1 angiotensin II (AT1 Ang II) receptor activation has been shown to
      cause increased vascular resistance in the systemic (SVR), pulmonary (PVR), and
      coronary vasculature which may be of particular importance in the setting of
      congestive heart failure (CHF). The overall goal of this study was to examine the
      effects of acute AT1 Ang II receptor inhibition on left ventricular (LV) pump
      function, systemic hemodynamics, and regional blood flow patterns in the normal
      state and with CHF, both at rest and with treadmill-induced exercise. METHODS AND
      RESULTS: Pigs (25 kg) were instrumented to measure cardiac output (CO), SVR, and
      PVR, and LV myocardial blood flow distribution in the conscious state and were
      assigned to one of two groups: (1) pacing-induced CHF (240 bpm for 3 weeks, n =
      6) or (2) sham controls (n = 5). Measurements were obtained at rest and after
      treadmill exercise (15 degrees for 10 minutes). Studies were repeated 30 minutes
      after intravenous infusion of a low (1.1 mg/kg) or high (125 mg/kg) dose of the
      AT1 Ang II antagonist, valsartan. The low dose of valsartan reduced the Ang II
      pressor response by approximately 50% but had a minimal effect on arterial
      pressure, whereas the high dose eliminated the Ang II pressor response and
      reduced resting blood pressure by approximately 20%. With CHF, CO was reduced at
      rest (2.5+/-0.2 v 3.9+/-0.1 L/min) and with exercise (6.4+/-0.5 v 7.8+/-0.5
      L/min) compared with controls (P < .05). Valsartan at the low and high dose
      increased resting CO by 28% in the control and CHF groups, but did not affect CO
      with exercise. Resting SVR in the CHF group was higher than controls (2,479+/-222
      v 1,877+/-65 dyne x s x cm(-5), P < .05), but SVR fell to a similar degree with
      exercise (1,043+/-98 v 1,000+/-77 dyne x s x cm(-5)). The low and high dose of
      valsartan reduced resting SVR by more than 30% in both the control and CHF
      groups. PVR was increased by more than twofold in the CHF group at rest. The high
      dose of valsartan reduced resting PVR with CHF, but had no further effect with
      exercise. LV myocardial blood flow was reduced with pacing CHF, particularly with
      exercise. With exercise and CHF, a low or high dose of valsartan reduced coronary
      vascular resistance, but LV myocardial blood flow remained reduced from normal
      values. CONCLUSIONS: Heightened AT1 Ang II receptor activity occurred in this
      model of CHF, which contributed to alterations in systemic hemodynamics and
      vascular resistive properties. By using a low dose of a selective AT1 Ang II
      receptor antagonist reduced SVR, PVR, and coronary vascular resistive properties
      and therefore may provide beneficial effects in a setting of CHF.

PMID- 9924854
TI  - Angiotensin AT1 receptor inhibition, angiotensin-converting enzyme inhibition,
      and combination therapy with developing heart failure: cellular mechanisms of
      action.
AB  - BACKGROUND: Past studies have shown that angiotensin-converting enzyme inhibition
      (ACEI) alone, angiotensin AT1 receptor blockade (AT1 block) alone, and combined
      treatment have differential effects on left ventricular (LV) function and
      geometry with developing congestive heart failure (CHF). The purpose of this
      study was to more carefully examine the cellular basis for these differential
      effects by using a model of pacing CHF. METHODS AND RESULTS: Pigs were randomly
      assigned to five groups: (1) rapid pacing (240 bpm) for 3 weeks (n = 9), (2)
      concomitant ACEI (benazeprilat, 0.187 mg/kg/day) and pacing (n = 9), (3)
      concomitant AT1 block (valsartan, 3 mg/kg/day) and pacing (n = 9), (4)
      concomitant ACEI and AT1 receptor blockade (benazeprilat/valsartan, 0.05/3
      mg/kg/day, respectively) and pacing (n = 9), and (5) sham controls (n = 10). The
      dosage protocol was based on obtaining a 50% reduction in angiotensin I and
      angiotensin II pressor response with no significant effects on mean basal
      arterial pressure. In the pacing group, LV fractional shortening (LVFS) fell
      compared with control group (13.4+/-1.4 v 39.1+/-1.0%, P < .05). With AT1 block,
      LVFS was unchanged from pacing only. ACEI and combined treatment increased LVFS
      from pacing values (25.2+/-0.9 v 20.9+/-1.9%, respectively, P < .05). LV myocyte
      shortening velocity was reduced with chronic pacing compared with control group
      (27.2+/-0.6 v 58.6+/-1.2 microm/s, P < .05) and remained reduced with AT1 block
      (28.0+/-0.5 microm/s, P < .05). Myocyte shortening velocity increased with ACEI
      or combination treatment (36.9+/-0.7 v 42.3+/-0.8 microm/s, respectively, P <
      .05). Concomitant treatment with either ACEI or AT1 blockade normalized myocyte
      action potential duration. In the combined ACEI and AT1 blockade group, all
      parameters of the myocyte action potential were unchanged from control values.
      CONCLUSIONS: This study showed that combined ACEI and AT1 receptor blockade
      produced beneficial effects on myocyte contractility and electrophysiology when
      compared with either monotherapy alone and therefore may provide unique benefits
      with CHF.

PMID- 9924855
TI  - Isoform-specific alterations in cardiac and erythrocyte Na+,K+-ATPase activity
      induced by norepinephrine.
AB  - BACKGROUND: Myocardial Na+,K+-ATPase activities are decreased in congestive heart
      failure because of an increase in plasma norepinephrine levels, but it is
      difficult to monitor the activities in the clinical setting. METHODS AND RESULTS:
      This study investigated whether erythrocyte Na+,K+-ATPase activity can reflect
      myocardial enzyme activity and whether isoform-specific alterations occur in the
      presence of catecholamine. Na+,K+-ATPase activity was measured by the
      colorimetric method by using the left ventricular myocardium and erythrocytes
      prepared from eight rabbits given norepinephrine for 7 days and from eight
      control rabbits that received saline. The protein levels of total catalytic
      subunit and alpha1- or alpha3-isoform of Na+,K+-ATPase were determined by Western
      blot analysis. Na+,K+-ATPase activity was lower in both myocardium and
      erythrocytes from norepinephrine-treated rabbits than control rabbits (P < .01
      and P < .01, respectively). There was a close correlation in Na+,K+-ATPase
      activity between myocardium and erythrocytes (r = .963). Total catalytic subunit
      protein level was lower in myocardium from norepinephrine-treated rabbits than
      control rabbits, but the alpha1-isoform level was similar between the two groups.
      The alpha3-isoform level was lower in norepinephrine-treated rabbits than control
      rabbits. In erythrocytes, alpha1-isoform was lower in norepinephrine-treated
      rabbits than control rabbits. CONCLUSIONS: Na+,K+-ATPase activity in myocardium
      could be reflected in erythrocyte membrane, although there was a difference in
      isoform-specific regulation between the two.

PMID- 9924856
TI  - New method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy
      material.
AB  - BACKGROUND: Excessive lengthening of cardiac myocytes attributed to series
      addition of sarcomeres is a consistent feature of left ventricular dilation in
      chronic heart failure. Currently, it is not feasible to assess myocyte
      dimensions, particularly myocyte length, in a manner that is of potential
      diagnostic usefulness. METHODS AND RESULTS: Isolated myocytes from three groups
      of normal rats (100, 200, and 300 g) were obtained by using two different
      methods: (1) digestion of formalin-fixed myocardial tissue using potassium
      hydroxide (KOH) and (2) retrograde aortic perfusion of fresh hearts with
      collagenase. There was no difference in mean cell length between the two methods.
      The KOH method was also used to isolate intact, rod-shaped myocytes from formalin
      fixed human cadaver left ventricles (control, n = 3; heart failure, n = 3) and
      from human right ventricle biopsy specimens (n = 6). Confirming our previous work
      using collagenase-isolated myocytes from fresh human explants, left ventricular
      myocytes from failing hearts showed longer mean cell length compared with control
      hearts. Data from human right ventricle biopsy specimens confirmed our previous
      finding in rats that myocyte lengthening is less pronounced in this chamber in
      heart failure. CONCLUSIONS: The KOH method can be used to obtain reliable
      measurements of myocyte length and other cellular parameters from myocardial
      biopsies and autopsy material. Such data may be useful in the diagnostic
      assessment of remodeling associated with heart failure.

PMID- 9924857
TI  - Genetically engineered mice: model systems for left ventricular failure.

PMID- 9924858
TI  - Who is managing your care?

PMID- 9924859
TI  - Pregnancy after loss.

PMID- 9924860
TI  - Internet technology: resources for perinatal nurses.
AB  - The Internet and the World Wide Web (WWW) are being discussed in many forums.
      This huge body of information is becoming a widely used research tool. Within the
      last few years, the WWW has grown enormously. In 1993, there were approximately
      130 WWW sites. By 1997, experts estimated there were over a million sites on the
      web, many of them useful for nurses and accessible from the nearest computer. For
      perinatal nurses in practice, research, or education the need for information is
      great. Nurses need current data for clinical decision making, policy writing,
      patient education, continuing education, and research. Understanding how to use
      the Internet, being aware of its advantages and disadvantages, and knowing how to
      critically examine what is available will assist perinatal nurses in making use
      of this newest form of information technology.

PMID- 9924861
TI  - Uterine myomas: treatment options.
AB  - Myomas (also called fibroids) are the most common solid pelvic tumors. Treatment
      options for myomas include medical and surgical management. The goals of medical
      management are to shrink the myoma and reduce its blood supply. Surgical
      interventions include therapies for women who wish to preserve fertility or
      retain their uterus. Newer treatment options include myomectomy achieved through
      an abdominal, laparoscopic, or hysteroscopic approach. Nurses assess and counsel
      women regarding treatment options.

PMID- 9924862
TI  - Home visits: strategies to protect the breastfeeding newborn at risk.
AB  - The breastfeeding mother whose infant is at risk for lactation failure that may
      lead to dehydration, weight loss, and hyperbilirubinemia can be assisted and
      supported in the home by maternal-child nurses, certified as lactation
      consultants, working collaboratively with the attending physician, midwife, or
      nurse practitioner. In this article, case reports illustrate interventions
      carried out in the home. Risk factors and clinical indicators of breastfeeding
      problems usually are present before hospital discharge. Health care providers
      should be on the alert for them so that management strategies can be started
      immediately after hospital discharge to ensure good patient outcomes.

PMID- 9924863
TI  - Physical activity and postpartum well-being.
AB  - OBJECTIVE: To describe reported patterns of postpartum physical activity and to
      identify benefits or risks associated with postpartum physical activity at 6
      weeks postpartum. DESIGN: Secondary analysis of longitudinal data collected
      prenatally and postpartum in a study of obstetric outcomes at a midwestern
      tertiary-care center and its ambulatory satellite and hospital clinics.
      PARTICIPANTS: One thousand three women completed a questionnaire at the 6-week
      postpartum clinic visit. Mean age was 29.7 years, and mean education level was
      15.3 years. VARIABLES OF INTEREST: Participation in vigorous exercise, change in
      postpartum activity level, postpartum weight retention, infant feeding method,
      maternal postpartum adaptation, and participation in activities for fun. RESULTS:
      Nearly 35% reported doing vigorous exercise with a modal frequency of three times
      per week. More active women had retained significantly less weight (8.6 lb [3.9
      kg]) than their less active counterparts (11.3 lb [5.1 kg]). Vigorous exercisers
      demonstrated a consistent pattern of better scores on measures of postpartum
      adaptation and were more likely than nonexercisers to participate in fun
      activities, such as socializing, hobbies, and entertainment. Breastfeeding was
      not adversely affected by vigorous exercise. CONCLUSIONS: These exploratory
      results indicate that physical and psychologic benefits may accrue to postpartum
      women who are able to exercise vigorously and avoid decreasing their usual level
      of activity. A prospective randomized test of this relationship is warranted.
      Although positive outcomes of physical activity have been demonstrated in the
      population at large, exercise has rarely been an element in postpartum care
      plans. Nurses who care for women after childbirth should assess women's exercise
      goals and support them in their desired activities.

PMID- 9924865
TI  - Individual, family, and relationship predictors of young women's sexual risk
      perceptions.
AB  - OBJECTIVE: To identify the individual, dyad, and family variables that influence
      young women's perceptions of risk for sexually transmitted diseases (STDs),
      including human immunodeficiency virus (HIV). DESIGN: Cross-sectional telephone
      survey using forced-choice questioning. Data were analyzed using first-order
      correlations and logistic regression. SETTING: Participants were recruited from a
      mid-Atlantic study of young adults and from volunteers at a mid-Atlantic
      university and surrounding community. PARTICIPANTS: A convenience sample of 93
      sexually active, unmarried, heterosexual women, ages 17-26 years. The majority of
      the study sample was white. MAIN OUTCOME MEASURE: Respondents were asked to
      estimate their own level of risk for STDs, including HIV, using the responses no,
      low, moderate, and high risk. Responses were later recoded into no risk versus
      some risk. RESULTS: Communication with parents about sexual risk decreased the
      odds that women would see themselves as being at no risk. Consistent condom use,
      relationship satisfaction, and perceiving the partner as no risk increased the
      odds that women would believe they were at no risk. CONCLUSIONS: Nurses can
      incorporate these and other study findings into the design of sexual risk
      reduction programs. Programs that enhance parent-teen communication about sexual
      risks and assist young women to examine their perceptions of their partners may
      be more effective than programs that provide information only.

PMID- 9924864
TI  - An early intervention program for adolescent mothers: a nursing demonstration
      project.
AB  - OBJECTIVE: To improve health outcomes in a vulnerable population of adolescent
      mothers and their infants. DESIGN: Effects of an intensive early intervention
      program (EIP) are compared with those of traditional public health nursing (TPHN)
      care. SETTING: A large California county with urban and rural communities, an
      ethnically diverse population, and a high teen birth rate. PARTICIPANTS: One
      hundred twenty-one young mothers and their children from impoverished and
      predominantly minority backgrounds. INTERVENTIONS: During pregnancy and through 1
      year postpartum, participants (n=63) in the EIP were provided with 4 prenatal
      classes and approximately 17 home visits by specially trained public health
      nurses. Interventions addressed health issues, sexuality and family planning,
      life skills, the maternal role, and social support systems. Participants in TPHN
      (n=58) received three home visits (for intake, prenatal care, and postpartum/well
      baby care information). MAIN OUTCOME MEASURES: Antepartum, intrapartum, and
      newborn medical records; maternal responses to written questionnaires; and nurse
      interviews. RESULTS: Early program outcomes indicate reduced premature birth
      rates for both groups compared with national data on adolescent mothers, and
      fewer days of infant hospitalization during the first 6 weeks postpartum for the
      EIP participants. CONCLUSION: Public health nurse care (both traditional and
      intensive) significantly improved perinatal outcomes; the intensive intervention
      significantly reduced the number of infant hospitalization days.

PMID- 9924866
TI  - SIDS risk factor awareness: assessment among nursing students.
AB  - OBJECTIVE: To test the hypotheses that nursing students (a) have limited
      knowledge of risk factors for sudden infant death syndrome (SIDS) and the
      American Academy of Pediatrics (AAP) recommendation of placing infants on their
      backs or sides for sleep, and (b) after careful education about SIDS, would
      retain this information and teach it to parents. DESIGN: A pretest questionnaire
      was used to identify knowledge of 13 risk factors and personal recommendation for
      sleep position. Participants attended a lecture on SIDS and received written
      educational material. A posttest was completed after 6 weeks. SETTING: Nursing
      students were assessed during their family practice course. PARTICIPANTS: Fifty
      one 4th-year nursing students (mean age 28.4 years, SD=7.6) enrolled in the BSN
      program completed the pretest; 29 completed the identical posttest. INTERVENTION:
      A lecture on SIDS and SIDS risk factors with written educational material after
      the pretest. MAIN OUTCOME MEASURES: Pretest and posttest responses. RESULTS: The
      Mann-Whitney test and McNemar chi-square analyses were used to determine factors
      on the pretest which influenced the awareness of prone position and to compare
      pretest and posttest data. On the pretest, 69% of students were aware of the AAP
      recommendation but significantly more (92%) were aware on the posttest. Posttest
      responses increased significantly for 12 of the 13 risk factors; 41% of the
      students identified all 13 risk factors on the posttest, in contrast to 0% on the
      pretest. On both the pretest and posttest, 93% of students stated that it was
      important to discuss their infant's sleep position with parents. Posttest results
      showed that students unanimously recommend the side or back sleep position.
      CONCLUSION: Nursing students were aware of the AAP recommendation, yet their
      knowledge of other risk factors was limited. A careful educational process
      resulted in retention of information about the AAP recommendation and other risk
      factors. In addition, students were willing to teach parents to place their
      infants on the back or side to sleep.

PMID- 9924867
TI  - Clinical approaches in the assessment of childbearing fatigue.
AB  - Modifications of the Fatigue Symptoms Checklist can be used clinically to assess
      fatigue during the childbearing year. Data from a series of studies provide
      beginning norms that can be used to interpret clinical scores and point to the
      potential importance of assessments to pregnancy complications and maternal
      performance. Consistent with North American Nursing Diagnosis Association (NANDA)
      definition of fatigue and the theory of unpleasant symptoms, fatigue and
      performance are important phenomena critical to the experience of pregnancy and
      assumption of the maternal role.

PMID- 9924868
TI  - Differential diagnosis of fatigue in women.
AB  - The incidence of fatigue among women has been reported to be higher than among
      men. Life events such as childbirth, menopause, and socially imposed roles may
      confer unique vulnerability. Effective treatment of fatigue is dependent on
      accurate diagnosis. The mechanisms of fatigue are not well understood, but
      physiologically based fatigue can be differentiated from psychogenic fatigue.
      Such differentiation helps to direct and enhance the effectiveness of
      interventions.

PMID- 9924869
TI  - What happens when fatigue lingers for 18 months after delivery?
AB  - OBJECTIVE: To understand the consequences when mothers experience fatigue
      throughout the first 18 months after birth. DESIGN: Secondary analysis of data
      from a longitudinal study. Fatigue was measured five times between birth and 18
      months after delivery. SETTING: Data for the longitudinal study were collected in
      different settings (hospital, telephone, and homes). PARTICIPANTS: White mothers
      who delivered full-term neonates of normal birth weight in a community hospital
      (N=229). MAIN OUTCOME MEASURES: Persistent fatigue was operationally defined as
      the report of at least one symptom of fatigue at all five time periods. The
      association between persistent fatigue and performance outcomes (maternal health,
      infant health, and infant development) was tested. RESULTS: Results were
      significant using alpha of .05. Persistent fatigue is associated with perceived
      maternal health and infant development at 18 months but not infant health.
      CONCLUSIONS: Findings suggest that persistent fatigue may have a negative effect
      on performance outcomes for mothers and infants. Assessment for fatigue symptoms
      should be part of each nursing contact and interpreted as a pattern. Helping
      mothers choose methods of symptom relief and energy conservation can benefit both
      the mother and the infant.

PMID- 9924870
TI  - Birth-related fatigue in 34-36-week preterm neonates: rapid recovery with very
      early kangaroo (skin-to-skin) care.
AB  - OBJECTIVE: To test preterm neonates' physiologic and behavioral responses when
      placed skin-to-skin on their mother's chests, called kangaroo care (KC), for the
      first 6 hours after birth, instead of having the neonates go to an intensive care
      unit. DESIGN: Convenience sampling was used in this descriptive study to enroll
      neonates who were given continuous KC beginning soon after birth in the delivery
      room and continuing for 6 hours. Heart rate, respiratory rate, oxygen saturation,
      abdominal temperature, and behavioral state were recorded each minute. SETTING:
      Data were collected in the delivery room and in a private labor room in tropical
      Cali, Colombia. PARTICIPANTS: Six 34-36-week preterm neonates with 5-minute APGAR
      scores of 6 or more were enrolled. Two neonates had grunting respirations before
      KC was begun. RESULTS: Temperature rose rapidly to thermoneutral range. With few
      exceptions, heart rate, respiratory rate, and oxygen saturation remained within
      normal limits; grunting respirations in two neonates disappeared with warmed
      humidified oxygen and continuous KC. Sleep predominated, and neonates were
      discharged home by 48 hours being fully breastfed, suggesting that KC was an
      environment conducive to recovery from fatigue. CONCLUSIONS: These data suggest
      that KC beginning in the delivery room can be given safely and perhaps with
      benefit to 34-36-week gestation neonates who appear healthy at birth. Kangaroo
      care was conducive to recovery from birth-related fatigue.

PMID- 9924871
TI  - The cycloid type and its differentiation from core schizophrenia: a
      phenomenological approach.
AB  - The heterogeneity within schizophrenia or the group of schizophrenias remains a
      vexing and limiting problem. An alternative to the "classic" explanatory
      construct of a schizophrenic unitary psychosis is the current concept of a
      positive/negative dichotomy with or without mixed type. However, the validation
      by findings from brain imaging, specificity, and prognostic validity of these
      multiple-entity approaches are still uncertain. Psychopathology is challenged to
      identify discrete types as homogenous as possible, providing closer relationship
      to distinct disease processes. Such types are to be defined by one or more axial
      syndromes, syndromes in an essential, not correlative, sense. One of these types
      is embraced by the term cycloid psychosis, implying a good prognosis. Using an
      integrative phenomenological methodology, the present study is able to show the
      specific quality of phenomena occurring in this type to pinpoint their "inner"
      relationships and to demonstrate cycloid syndromes as axial syndromes in the
      phenomenological sense. Thus, it is shown that positive symptoms in the cycloid
      type are different from those in core schizophrenia. In addition to the quality
      and inner coherence of the constituent elements, the absence of structural
      deformations of (1) emotional expression and affect, (2) thought, and (3)
      movement impulses and sequences is the decisive specificity feature that allows
      differentiation of the cycloid type from poor-prognosis core schizophrenia. These
      syndromes of structural deformations are the axial syndromes of core
      schizophrenia, occurring with or without "productive" (positive) phenomena. Its
      conceptualization makes a contribution to the actual negative-symptom discussion
      shifting the perspective from a low specific level (e.g., abulia) to phenomena of
      higher specificity. On the basis of a precise definition of cycloid axial
      syndromes, previous operationalization suggestions are reviewed and evaluated,
      and an alternative approach is outlined. Finally, it is hypothesized that the
      cycloid type may be a primary neurotransmitter disease, while core schizophrenia
      seems closer to the pathophysiological mechanisms described in Stevens' theory.

PMID- 9924872
TI  - The neuroleptic malignant syndrome: an Indian experience.
AB  - A study was performed to investigate the clinical presentation and outcome of the
      neuroleptic malignant syndrome (NMS) in a large teaching psychiatric hospital in
      India. Thirteen cases were identified after a thorough search of intensive care
      unit (ICU) records during the 4-year period between 1990 and 1993. Information
      collected from these cases was then compared against data from a representative
      control group of 252 inpatients who received neuroleptics, drawn randomly from
      each of the 4 years of the study. Statistical comparisons were made using
      Student's t test, the chi-square test, and Fisher's exact test. The incidence of
      NMS was 1.41 per 1,000 cases treated with neuroleptics (95% confidence interval,
      0.71 to 2.14 per 1,000) and the mortality from NMS was 38%. Patients who
      developed NMS had a significantly higher incidence of coexisting physical or
      neurological illness and received a higher mean neuroleptic dose. Neuroleptic
      loading rates were not different in the NMS and control samples. Fluphenazine
      decanoate was implicated as a causative factor of NMS in a significantly higher
      proportion of these patients. The group with a fatal outcome was significantly
      older and received a higher neuroleptic dose than the control group, but not
      compared with the group that recovered.

PMID- 9924873
TI  - Social adjustment and self-esteem in remitted patients with unipolar and bipolar
      affective disorder: a case-control study.
AB  - To evaluate social adjustment and self-esteem in patients with unipolar (UP) and
      bipolar (BP) affective disorder and to examine demographic and clinical
      correlates of these variables, outpatients with UP and BP disorder in remission
      for at least 12 months were consecutively recruited and individually matched to
      control subjects with no personal or family history of psychiatric illness (UP
      control matched pairs, n = 23; BP-control matched pairs, n = 27). Subjects
      completed the Rosenberg Self-Esteem scale (SES) and the self-report version of
      the Social Adjustment Scale (SAS). UP patients reported significantly worse
      overall social adjustment than their matched controls (P = .009), specifically in
      the area of social and leisure activities (P = .0003) and poorer self-esteem (P =
      .02). When separated by gender, only the female UP group manifested significant
      findings on the SAS. BP patients reported poorer self-esteem than their controls
      (P = .04), but were not significantly different on the SAS. Although the patients
      were not clinically depressed, a worse social adjustment was significantly
      associated with a higher score on the Hamilton Depression Scale (HAM-D) in both
      groups. In the UP group, this association was absent when the analysis was
      limited to patients receiving antidepressant pharmacotherapy. The findings
      indicate that (1) UP patients, particularly women, experience substantial
      difficulties in social adjustment, primarily in social and leisure activities,
      even during stable clinical remission, and (2) in both UP and BP patients,
      adjustment problems are related to depressive symptoms even though these are
      minimal in severity.

PMID- 9924874
TI  - Recurrent major depressive disorder among human immunodeficiency virus (HIV)
      positive and HIV-negative intravenous drug users: findings of a 3-year
      longitudinal study.
AB  - A longitudinal study was conducted to investigate the association between human
      immunodeficiency virus (HIV) infection, history of major depressive disorder
      (MDD), and persistent or recurrent MDD among intravenous drug users. Psychiatric
      disorders were assessed in a sample of HIV-positive (HIV+) and HIV-negative (HIV
      ) intravenous drug users every 6 months for 3 years. Results indicated that HIV
      status and baseline MDD independently predicted persistent or recurrent episodes
      of MDD after gender, drug use, ethnicity, income, and the presence other
      psychiatric disorders were controlled statistically. Among HIV+ intravenous drug
      users with baseline MDD, 90% experienced at least one subsequent episode of MDD
      and 47% experienced at least three subsequent episodes of MDD. However, less than
      40% of intravenous drug users with current MDD received treatment for emotional
      problems. These findings indicate that intravenous drug users with HIV infection
      and a history of MDD are at considerable risk for future episodes of MDD or
      recurrent MDD, and that increased provision of treatment for intravenous drug
      users with MDD may be necessary.

PMID- 9924876
TI  - Predictors of 1-year outcome for patients with panic disorder.
AB  - The course of panic disorder (PD) is often prolonged, but factors that affect the
      social outcome have not yet been made clear. The aim of this study was to find
      predictors of outcome for patients with PD. The subjects were 65 outpatients (28
      men and 37 women) with PD (DSM-III-R) who were treated at our hospital for more
      than 1 year. The factors affecting 1-year outcome were evaluated by multiple
      regression analysis. We found that the following were predictors of poor social
      outcome in PD: (1) severe agoraphobia at the first psychiatric examination and
      (2) long duration of illness before the first psychiatric consultation.
      Furthermore, the complication of hypochondriacal symptoms predicted a poor
      outcome for PD. Early attention to agoraphobia and hypochondriasis is essential
      for the treatment of PD, and early introduction to psychiatric treatment is
      recommended.

PMID- 9924875
TI  - Panic disorder and cigarette smoking behavior.
AB  - Smoking has been discussed both as a risk factor for panic disorder and as a
      contributing factor to elevated cardiovascular risk in panic disorder patients.
      Smoking habits and their association with panic disorder were studied in a sample
      of 102 panic disorder patients. Both for female and for male patients, rates of
      smokers and of exsmokers were substantially higher than in the general
      population. However, a surprisingly high number of patients had succeeded in
      reducing or quitting cigarette smoking because of their panic disorder, although
      they experienced little benefit in regard to panic symptoms from doing so. We
      conclude that the motivation for changing smoking habits is high in this
      population with elevated smoking prevalence and should be taken into
      consideration by therapists.

PMID- 9924877
TI  - Order of onset of substance abuse and depression in a sample of depressed
      outpatients.
AB  - Drug abuse has been thought to cause depression, or to serve as a form of self
      medication for depression. Our objective was to examine whether specific types of
      drug abuse preceded or followed the onset of depression. A retrospective, blinded
      case-controlled assessment of the drug and depressive history of depressed
      outpatients was conducted. Three hundred seventy-five patients with major
      depressive disorder were evaluated for comorbid drug dependence using the
      Structured Clinical Interview for DSM-III-R (SCID). They were selected from the
      psychiatric outpatient department of a metropolitan teaching hospital and grouped
      into homogeneous classes of drug dependence including alcohol, cannabis, cocaine,
      amphetamine, LSD, hypnosedative, opiate, and polysubstance use. We determined the
      percent of depressed patients with each specific type of drug abuse, their age of
      onset of depression and onset of specific drug abuse, and the mean number of
      lifetime depressive episodes for each patient. We found that alcohol dependence
      followed the onset of first life depression by 4.7 years (P = .02, two-tailed).
      Among polydrug-dependent patients, each drug abused followed the onset of
      depression, except for LSD, which coincided with the onset of depression. Among
      polydrug users, cocaine dependence occurred 6.8 years after the first major
      depressive episode (P = .007) and alcohol dependence 4.5 years after the onset of
      depression (P = .007). Opiate and sedative users had the least number of lifetime
      depressive episodes (3.7), and LSD and cocaine users had the greatest number
      (12.2). We conclude that alcohol and cocaine use in this sample of depressed
      outpatients conformed to a pattern of self-medication.

PMID- 9924878
TI  - Comparison of buying behavior in depressed patients presenting with or without
      compulsive buying.
AB  - Compulsive buying is defined as repetitive impulsive and excessive buying leading
      to personal and familial distress. This study compares the buying behavior of
      depressed patients presenting with or without compulsive buying. The weight of
      promotional factors such as sales and advertising campaigns was systematically
      assessed. The impulsive nature of compulsive buying and the choice of items
      purchased were also investigated. For this purpose, we studied buying behavior
      among 52 inpatients diagnosed for major depressive episode with DSM-IV criteria.
      None of the patients presented mania or hypomania, obsessive-compulsive disorder,
      or alcohol or drug abuse or dependence disorder. We assessed the prevalence of
      compulsive buying and compared the "buying style" among patients with (CB+) and
      without (CB-) compulsive buying. The diagnosis of depression was assessed with
      the Mini International Neuropsychiatric Interview (MINI). The diagnosis of
      compulsive buying was made using standardized criteria and a specific rating
      scale. All patients answered a specific questionnaire assessing the phenomenology
      of the buying behavior. Twenty-one of 52 depressives presented with compulsive
      buying. The CB+ group was not more sensitive to promotional factors. They did not
      seek sales or use loans significantly more than others. Upon entering a shop, the
      CB+ subjects did not change their choice more often than others. CB+ subjects
      were significantly more often alone while shopping (85% of cases v61% of CB-
      group, p = .05). Most purchases from the CB+ group were self-gifts or gifts to
      others (50.4% v 23.5%, p = .003); 14.4% of purchases in the CB+ group (v 2.2% in
      CB- group, P = .045) were made because the patients believed their social status
      requires acquisition. Items to be bought were more often considered by CB+
      subjects as occasions not to be missed (31.4% v15.1%, P = .03). Purchases were
      significantly (57% v 16%) less often used than expected by the CB+ group (P =
      .002). Most purchases, in addition, represented gifts for oneself or others and
      were used significantly less often than expected.

PMID- 9924879
TI  - Different types of self-injurious behavior in bulimia nervosa.
AB  - In a previous study, we demonstrated the validity of the distinction, in bulimia
      nervosa (BN), between compulsive self-injurious behavior (SIB), such as hair
      pulling and onycophagia, and impulsive SIB, such as skin cutting and burning. The
      aim of the present study is to investigate the clinical and psychological
      correlates of these two categories of SIB in BN. The sample consisted of 175
      consecutive patients with BN, diagnosed according to DSM-IV criteria. Subjects
      were assessed by means of a semistructured interview and self-reported
      questionnaires (Eating Disorders Inventory [EDI] and Hopkins Symptom Checklist
      [SCL-90]). In our sample, impulsive SIB appeared to be associated with suicide
      attempts, a history of sexual abuse, and depression. On the other hand,
      compulsive SIB seemed to be related to a lack of awareness towards emotions and
      body sensations, greater obsessionality, and a shorter duration of illness.

PMID- 9924880
TI  - A mathematical typology analysis of DSM-III-R personality disorder
      classification: grade of membership technique.
AB  - This study employed grade of membership (GoM) analysis in a clinical setting to
      determine if the DSM-III-R personality disorder (PD) diagnostic criteria cluster
      into recognizable disorders resembling the official axis II nosology. The GoM
      model, based on fuzzy-set theoretic concepts, explicitly examines medical
      diagnostic systems by quantitatively identifying and characterizing subpatterns
      of illness within a broad class. A semistructured assessment of 110 outpatients
      was performed for 12 PDs and their 112 diagnostic criteria. GoM analysis was
      performed using internal variables of the 112 PD criteria rated as present or
      absent. Demographic variables, axis I and II diagnosis (structured clinical
      Interview for DSM [SCID]), and treatment response (Global Adjustment Scale [GAS])
      information were used as external validators. Four pure types (PT) provided the
      most satisfactory solution to the data. PT-I is characterized by marked
      maladaptive personality pathology, which is manipulative, egocentric, impulsive,
      and alloplastic. PT-II consists primarily of exaggerated socially anxious and
      detached traits. PT-III is sociably dependent and autoplastic. PT-IV is
      essentially asymptomatic. GoM provides a more parsimonious handling of the PD
      criteria than provided by classifying according to DSM categories. The analysis
      fails to confirm the natural occurrence of any single specific axis II PD or
      cluster.

PMID- 9924881
TI  - Latent structure analysis of DSM-IV borderline personality disorder criteria.
AB  - The aim of this study was to evaluate the structure of DSM-IV borderline
      personality disorder (BPD) criteria. The study group consisted of 564
      consecutively admitted inpatients and outpatients. BPD criteria discriminatory
      power was tested by using corrected item-to-total and item-to-diagnosis
      correlations. Weighted least-squares (WLS) confirmatory factor analysis (CFA) was
      used to assess the fit of DSM-IV BPD unidimensional model. The categorical model
      of BPD was tested by exploratory latent class analysis (LCA). Item analysis
      suggested a hierarchy in BPD criteria discriminatory power, even if with
      different rank order with respect to the DSM-IV model. CFA showed a unifactorial
      structure with congeneric items as the best fitting model for DSM-IV BPD criteria
      (chi2 = 18.89, df= 27, P > .87). LCA showed evidence for three latent classes;
      heterogeneity was observed only among subjects falling below DSM-IV diagnostic
      threshold for BPD. These results support the categorical model of BPD, even if
      with several differences with respect to DSM-IV.

PMID- 9924882
TI  - Atypical depression in private practice depressed outpatients: a 203-case study.
AB  - The prevalence of DSM-IV atypical depression and comparisons between atypical and
      typical depression were studied in 203 consecutive unipolar and bipolar depressed
      outpatients presenting for treatment of depression in private practice. The
      prevalence of atypical depression was 31%. Of the variables investigated
      (unipolar/bipolar diagnosis, age at baseline/onset of first major depressive
      episode, gender, psychosis, comorbidity, chronicity, duration of illness,
      recurrence, and severity), a bipolar II diagnosis was significantly more common,
      the age at baseline and duration of illness were significantly lower, and the
      proportion of females and psychiatric comorbidity were significantly higher in
      atypical versus typical depression. Secondary analysis showed that bipolar II
      atypical depression had a significantly earlier age at baseline/onset and
      affected more females, but there were no other significant differences versus
      typical depression. The findings suggest important clinical differences between
      atypical and typical depression, and a bipolar II subtype may be separated from
      the broad category of atypical depression.

PMID- 9924883
TI  - Increasing plasma neopterin and persistent plasma endothelin during follow-up
      after acute cerebral ischemia.
AB  - Release of inflammatory mediators from leukocytes and endothelial release of
      vasoactive factors are both important in the pathogenesis of atherosclerosis. To
      evaluate the concentrations of a specific marker for macrophage activation,
      neopterin, and the potent endothelial derived vasoconstrictive peptide endothelin
      1 (ET-1), during the acute and chronic stages of cerebral ischemia, plasma
      concentrations of neopterin and ET-1 were measured in 59 patients with acute
      cerebral infarction or transient ischemic attack (median age 73 years, range 43
      93, 27 men) and after a 1-year follow-up in 57/59 (97%) of patients. Plasma
      neopterin was higher at follow-up (6.3 nmol/L [3.7-21.6] vs 5.6 nmol/L [3.5
      17.2]; p < 0.05) than at the acute stage, whereas the plasma ET-1 concentration
      was unchanged. Plasma concentrations of both neopterin and ET-1 correlated
      directly with age both in the acute stage (r = 0.42 and r = 0.35, respectively; p
      < 0.01) and after follow-up (r = 0.34; p < 0.05 and r = 0.27; p = 0.05,
      respectively). In conclusion, plasma neopterin increased after acute cerebral
      ischemia, indicating chronic inflammatory activity and continuous macrophage
      activation in ischemic cerebrovascular diseases.

PMID- 9924885
TI  - Smooth muscle differentiation in human vein wall at valvular level: comparison
      with nonvalvular wall and correlation with venous function.
AB  - The aim of this study was to evaluate local differences in smooth muscle
      differentiation in venous valves of patients suffering from chronic venous
      insufficiency, in relation to functional hemodynamic parameters measured by echo
      Doppler. These functional parameters did not correlate with smooth muscle
      differentiation at the valvular site. These results failed to support an
      initiating role of valvular structure in the development of chronic venous
      insufficiency. However, this work stresses differences in cellular
      differentiation of valve wall and nonvalvular smooth muscle cells in culture, and
      we found histologic differences in the structure of endovein and media
      (connective tissue relative content) between valvular and nonvalvular venous
      wall. The presence of smooth muscle cells in the valve cusp was demonstrated by
      smooth muscle alpha-actin-specific labeling and was observed to be restricted to
      one side of the valve cusp.

PMID- 9924884
TI  - Carotid disease in patients scheduled for coronary artery bypass: analysis of 678
      patients.
AB  - The purpose of this article is to investigate the frequency of carotid disease
      and to identify high-risk groups among patients scheduled for isolated coronary
      artery bypass grafting (CABG) procedures under nonemergent conditions. A total of
      678 consecutive patients underwent preoperative carotid artery duplex scanning
      (CADS) before CABG procedures. Morphology of carotid artery was determined and
      five groups were formed. Age, sex, cervical bruit, diabetes mellitus (DM),
      hypertension, smoking, history of cerebrovascular event (CVE), peripheral
      vascular disease (PVD), and severity of coronary artery disease were investigated
      to describe the high-risk group for carotid artery disease. In 41% of patients
      carotid examination produced normal findings; 46.2% had less than 60% luminal
      stenoses, 7.1% had 60-79% stenoses, 4.6% had 80-99% stenoses, and 1.2% had total
      occlusion. Previous cerebral ischemic events (CVE) (p<0.05), hypertension (p <
      0.01), smoking (p < 0.01), advanced age (p < 0.01), and female sex (p < 0.01)
      were identified as high-risk factors for carotid artery stenoses. There was a
      linear association between carotid disease and coronary disease (p < 0.05).
      Documentation of previous CVE, hypertension, smoking, advanced age, female sex,
      and severe coronary artery disease may be helpful in identifying patients at high
      risk for carotid artery stenoses.

PMID- 9924886
TI  - Diagnosis of deep venous thrombosis of the lower limbs: it is premature to
      introduce ultrasound as a routine method.
AB  - Ultrasound is sometimes employed as an alternative technique to phlebography in
      the diagnosis of deep venous thromboses (DVT). To evaluate the efficacy of
      ultrasound, 74 patients suspected of DVT in the lower limbs were examined with
      both ultrasound and phlebography. The results indicate that positive reports
      following ultrasound examination are reliable but that negative reports are not
      very dependable. The authors urge, therefore, a degree of caution before
      ultrasound is introduced as a routine method in hospital care.

PMID- 9924887
TI  - Early detection of anthracycline-induced cardiotoxicity by radionuclide
      angiocardiography.
AB  - For the early detection of myocardial damage associated with anthracycline
      therapy, electrocardiography, echocardiography, and radionuclide
      angiocardiography were used to assess cardiac function in 37 patients receiving
      anthracyclines (ie, adriamycin and daunorubicin at a total dose of 100-2,030
      mg/m2). None of the patients developed clinical congestive heart failure. There
      were no significant changes of electrocardiographic and echocardiographic
      parameters after anthracycline administration. The left ventricular ejection
      fraction did not change significantly on radionuclide angiocardiography. However,
      the 1/3 peak filling rate (PFR) corrected by the end-diastolic count (EDC) (1/3
      PFR/EDC) and the 1/3 filling fraction (1/3 FF), the indices of early diastolic
      function, showed a significant decrease. These findings suggest that the 1/3
      PFR/EDC and 1/3 FF determined by radionuclide imaging are useful for detecting
      silent myocardial damage induced by anthracyclines.

PMID- 9924888
TI  - Usefulness of cardiopulmonary bypass in reconstruction of inferior vena cava
      occupied by renal cell carcinoma tumor thrombus.
AB  - Aggressive surgical treatment in renal cell carcinoma is still controversial. The
      aim of this paper is to assess inferior vena caval (IVC) reconstruction for
      suprahepatic vena caval renal cell carcinoma (RCC) tumor thrombus. Twelve
      patients with suprahepatic vena caval thrombus from renal cell carcinoma who
      underwent surgical repair with cardiopulmonary bypass were evaluated. The vena
      caval defect was reconstructed by direct suture, patch repair, or graft
      replacement. Of 12 patients undergoing partial cardiopulmonary bypass, tumor
      thrombus extended to the junction of the hepatic vein in three patients and to
      the right atrium in one. Tumor thrombus was removed manually or with balloon
      catheter. Tumor thrombus in the right atrium was removed during electrical
      ventricular fibrillation. Repair of the IVC was performed by direct suture of the
      IVC wall in two patients, patch repair with expanded polytetrafluoroethylene
      (EPTFE) graft in seven, and graft replacement with an EPTFE graft in three. There
      were no operative deaths and the only postoperative complication was one patient
      death from pulmonary emboli. The four patients with nonlocalized disease died
      within 2 years, but four patients lived for more than 3 years postoperatively.
      Survival was 37.5% at 3 years and 18.8% at 5 years by the Kaplan-Meier's method.
      CONCLUSIONS: (1) Partial cardiopulmonary bypass is useful for the control of
      bleeding when tumor thrombus in the IVC extends to the junction of the hepatic
      vein. (2) Nephrectomy with tumor thrombectomy of the IVC is valuable, and long
      term survival is possible in patients without distant metastases or regional
      lymph node metastases.

PMID- 9924889
TI  - Accelerated coronary reperfusion through the use of rapid bedside cardiac markers
      -case reports.
AB  - Each year, acute myocardial infarctions (AMI) account for more than half a
      million deaths in the United States. Complicating treatment of AMI is the
      difficulty in accurately diagnosing the event, for patients have nondiagnostic
      electrocardiograms (ECG) more than 50% of the time. In this population, cardiac
      markers are essential to confirm the diagnosis. The new bedside cardiac markers,
      which use eight drops of whole blood and require 15 minutes to be read negative,
      make it possible to shorten time needed to diagnose AMI. One hundred twenty-seven
      consecutive patients presented to the emergency department complaining of
      atypical chest pain. All had ECGs that were nondiagnostic for myocardial
      infarction. Serial cardiac markers were performed: myoglobin, troponin I, rapid
      myoglobin, and rapid troponin I. One hundred eighteen patients with negative
      serial cardiac markers had exercise treadmill tests in the emergency department.
      Nine patients with positive serial cardiac markers received emergent primary
      angioplasty. Six of the nine patients were treated based on the positive results
      of the rapid bedside cardiac markers. A 100% correlation existed between the
      quantitative serum results and the rapid bedside markers. With the availability
      of rapid bedside assays, dependency on the laboratory can be minimized, since
      quantitative cardiac markers require at least 1 hour of turnaround time. Rapidly
      and correctly diagnosing AMIs in patients with ECGs nondiagnostic for AMI has
      always been a dilemma. Rapid bedside assays enable the physician to accurately
      diagnose myocardial infarction and safely decrease the time in evaluating chest
      pain, thus maximizing the benefits of early reperfusion.

PMID- 9924890
TI  - Primary stenting of the superior mesenteric artery for treatment of chronic
      mesenteric ischemia--a case report.
AB  - Percutaneous transluminal angioplasty (PTA) has been well described in the
      treatment of mesenteric artery stenoses but has met with limited success in
      ostial lesions. The authors describe a case of a 79-year-old woman diagnosed with
      chronic mesenteric ischemia associated with a 22-pound weight loss and
      postprandial pain. The celiac axis and inferior mesenteric artery were occluded.
      A high-grade, calcified stenosis was present in the proximal superior mesenteric
      artery. This was treated with primary stent placement using a Palmaz stent
      deployed from an axillary approach. A brief discussion of mesenteric ischemic and
      visceral artery PTA is included.

PMID- 9924891
TI  - Palmar aneurysm accompanied by ipsilateral clubbing finger--a case report.
AB  - A 33-year-old man presented with a palmar aneurysm accompanied by painful
      ipsilateral clubbing finger in his right hand. Following resection of the
      aneurysm and arterial reconstruction with a cephalic vein graft, the pain in his
      fingers disappeared. Histologic examination identified the resected tissue as a
      true aneurysm. The clubbing finger was ascribed to chronic ischemia due to a
      stenotic lesion associated with palmar arch hypoplasia and aneurysm. The
      following is the first reported case of palmar aneurysm accompanied by
      ipsilateral clubbing finger.

PMID- 9924892
TI  - Congenitally corrected transposition of the great arteries with a patent foramen
      ovale in an 81-year-old man--a case report.
AB  - Congenitally corrected transposition of the great arteries is a rare cardiac
      anomaly with a poor prognosis. In this report, the authors describe an 81-year
      old man admitted to the hospital with generalized fatigue, chest pain, and
      cyanosis. Computed tomography and cardiac catheterization revealed corrected
      transposition of the great arteries. Transesophageal echocardiography disclosed
      moderate right atrioventricular regurgitation and a right-to-left shunt across a
      patent foramen ovale during systole. Because this patient had no other congenital
      cardiac anomalies, the right-to-left shunt through the patent foramen ovale was
      thought to be the major cause of cyanosis.

PMID- 9924893
TI  - Absence of the azygos vein associated with double superior vena cava--a case
      report.
AB  - A rare case of absence of the azygos vein associated with double superior vena
      cava is presented. Imaging findings on plain chest film and on contrast-enhanced
      computed tomography are described, and the embryology of azygos and hemiazygos
      veins is reviewed.

PMID- 9924894
TI  - Titer of tumor necrosis factor receptor: can it be a predictor of the development
      of deep vein thrombosis and pulmonary embolism?

PMID- 9924895
TI  - Seizure-refractory period after a single stimulation and inhibition of seizures
      after repetitive stimulation in the gerbil: effects on blood cortisol levels.
AB  - PURPOSE: To determine the epileptic response of gerbils to external shock
      stimulus, assessing blood cortisol levels as a parameter to determine stress
      conditions. METHODS: Five sets of two-month-old Mongolian gerbils were stimulated
      to elicit seizures by the clapping of a sheaf of papers. Stimulation was done
      once a week over a 10-week period to obtain a stable situation and a similar
      response in all the animals. Four of the sets were killed to collect blood
      samples: those not manipulated; those stimulated twice a day for 5 days; those
      stimulated once to obtain samples immediately after seizure recovery; and those
      stimulated once to obtain samples 30 min after seizure recovery. Blood samples
      from the fifth set of animals were taken in vivo from the retro-orbital plexus.
      RESULTS: Eliciting seizures with this stimulus, twice a day in a repetitive way,
      prevented further induced seizures from the second day of stimulation on. Changes
      in the gerbils' behavior--from exploratory to escape mode--were also observed.
      The blood cortisol levels found in the sets of animals killed without induced
      seizures were similar to the others, regardless of whether the animals had been
      subjected to repetitive stimulation. Additionally, significant decreases in blood
      cortisol levels were detected in the animals killed immediately and 30 min after
      recovering from an induced epileptic episode. CONCLUSIONS: The normal refractory
      period in gerbils can be estimated at 1 h. The lack of correlation between
      cortisol levels and the inhibition of seizure-elicitation through repetitive
      stimulation supports the environmental and exploratory hypothesis of seizure
      generation rather than a stress hypothesis.

PMID- 9924896
TI  - The neuropathology of hyperthermic seizures in the rat.
AB  - PURPOSE: Single and repeated hyperthermic seizures were induced in rats beginning
      at age 22 days to determine the neuroanatomic consequences to the hippocampus and
      to compare these changes with those in the hippocampi of patients with temporal
      lobe epilepsy (TLE) experiencing febrile seizures. METHODS: Hyperthermic seizures
      were induced by placing rats in a bath of water at 45 degrees C for 4 min.
      Seizures were visually observed, and some animals also were monitored
      electroencephalographically. Neurodegeneration was examined with a silver stain,
      whereas granule cell sprouting was detected with the Timm stain. RESULTS: In a
      majority of rats, hyperthermia-induced tonic-clonic seizures ranged in duration
      from 30 s to 6 min; the seizure duration increased with the number of seizures.
      No neurodegeneration was detectable in these animals, although there was
      sprouting of granule cell collaterals into the inner molecular layer (IML) of the
      dentate. In a small number of animals, the short seizures evolved into status
      epilepticus, and neuronal degeneration was present in the hippocampus and other
      parts of the temporal lobe, and the mediodorsal thalamus. CONCLUSIONS: This study
      confirms the relation between hyperthermia and seizure occurrence. It shows in
      particular that, as in the human, only prolonged seizures such as status
      epilepticus cause a pattern of neurodegeneration similar to that observed in
      human TLE.

PMID- 9924897
TI  - Muscarinic receptors mediate carbachol-induced inhibition of maximal electroshock
      seizures in the nucleus reticularis pontis oralis.
AB  - PURPOSE: Previous reports from this laboratory indicated a role for N-methyl-D
      aspartic acid (NMDA) and gamma-aminobutyric acid (GABA) receptors among the
      neuronal mechanisms of the nucleus reticularis pontis oralis (RPO) that regulate
      the tonic hindlimb extension (THE) component of maximal electroshock seizures
      (MESs) in rats. This study was intended to determine the role of cholinergic
      mechanisms in the RPO regulation of THE. METHODS: Rats were surgically prepared
      with microinjection guide cannulas for the focal administration of drug solutions
      directly into the RPO. MES was induced with corneal electrodes. RESULTS: RPO
      microinjection of carbachol significantly inhibited the incidence of THE. RPO
      microinjection of atropine by itself had no effect on the seizure response but
      significantly antagonized the anticonvulsant effect induced by RPO microinjection
      of carbachol. The selective nicotinic agonist dimethylpiperizinium (DMPP) by
      itself had no effect on THE. RPO microinjection of 10 ng pertussis toxin by
      itself had no effect on THE but significantly antagonized the anticonvulsant
      effect induced by RPO microinjection of carbachol. CONCLUSIONS: RPO
      microinjection of carbachol inhibited the THE component of MESs in rats. The
      carbachol effect appeared to be mediated by muscarinic receptors as the
      anticonvulsant activity was antagonized by atropine, and the selective nicotinic
      agonist DMPP induced no anticonvulsant activity. Because pertussis toxin acts to
      inhibit muscarinic receptor-linked G proteins, the pertussis toxin antagonism of
      carbachol also supports a muscarinic mechanism of action.

PMID- 9924898
TI  - Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe
      epilepsy.
AB  - PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography
      (PET) reveals regional hypometabolism in 60-80% of patients with mesial temporal
      lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the
      epileptogenic zone. The pathophysiology underlying this widespread change is
      unknown. This study evaluated the relation between hippocampal neuronal loss and
      hypometabolism in patients with MTLE. METHODS: Forty-three patients with MTLE
      after anterior temporal lobectomy were included. Pathology demonstrated mesial
      temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET
      scans were graded by visual analysis on a scale ranging from normal (grade 1) to
      severe (grade 5) hypometabolism. Neuronal counting was performed in the
      subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal
      density of patients was compared with that of seven autopsy controls. Data were
      compared by using Student's t tests and Kruskal-Wallis one-way analysis of
      variance (ANOVA). RESULTS: Significant neuronal loss in CA1 through CA4 and DG
      was found in patients compared with controls. Neuronal density in the subiculum,
      CA1, CA4, and DG did not correlate with severity of hypometabolism. However,
      patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus
      patients with normal studies. CONCLUSIONS: This study supports a previous
      observation that degree of FDG-PET hypometabolism does not parallel severity of
      hippocampal neuronal loss in MTLE.

PMID- 9924899
TI  - NMDA-receptor activity visualized with (S)-[N-methyl-11C]ketamine and positron
      emission tomography in patients with medial temporal lobe epilepsy.
AB  - PURPOSE: To determine whether neurochemical activation of the N-methyl-D
      aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured
      as binding of 11C-labeled (S)-[N-methyl]ketamine, in patients with medial
      temporal lobe epilepsy (MTLE). METHODS: Eight patients with MTLE who were
      evaluated regarding epilepsy surgery underwent positron emission tomography (PET)
      with (S)-[N-methyl-11C]ketamine. The presurgical investigations included magnetic
      resonance imaging (MRI), PET with 18F-fluoro-deoxyglucose (18FDG), and seizure
      monitoring by using video-EEG. The uptake of (S)-[N-methyl-11C]ketamine in the
      temporal lobe of ictal onset was compared with the contralateral side and
      correlated to changes in regional glucose metabolism measured by PET with 18FDG.
      RESULTS: (S)-[N-methyl-11C]ketamine rapidly reached the brain, and high
      radioactivities were measured in the striatum, thalamic nuclei, and cortical
      regions. Overall the brain uptake and regional binding potentials of (S)-[N
      methyl-11C]ketamine were similar to measurements observed previously in healthy
      controls. However, 20 min after administration, when blood flow influence was
      negligible, a side-to-side comparison revealed a 9-34% reduction of tracer
      radioactivity in the temporal lobes of ictal onset. At earlier times, the
      differences in binding potentials were less pronounced, 9-21%. The magnitude and
      distribution of the reduction were similar to the metabolic pattern seen on PET
      scans with 18FDG. CONCLUSIONS: Radioactivity uptake of intravenously administered
      (S)-[N-methyl-11C]ketamine was reduced in temporal lobes of ictal in patients
      with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion,
      focal atrophy, or other factors.

PMID- 9924900
TI  - Muscarinic receptor loss and preservation of presynaptic cholinergic terminals in
      hippocampal sclerosis.
AB  - PURPOSE: Prior single-photon emission tomography studies showed losses of
      muscarinic acetylcholine receptor (MAChR) binding in patients with refractory
      mesial temporal lobe epilepsy. Experimental animal studies demonstrated transient
      losses of MAChR due to electrically induced seizures originating in the amygdala.
      However, the relations between cholinergic synaptic markers, seizures, and
      underlying neuropathology in human temporal lobe epilepsy are unknown. We tested
      the hypotheses that human brain MAChR changes are attributable to hippocampal
      sclerosis (HS), and that HS resembles axon-sparing lesions in experimental animal
      models. METHODS: We measured MAChR binding-site density, an intrinsic neuronal
      marker, within the hippocampal formation (HF) in anterior temporal lobectomy
      specimens from 10 patients with HS and in 10 autopsy controls. Binding-site
      density of the presynaptic vesicular acetylcholine transporter (VAChT) was
      measured as a marker of extrinsic cholinergic afferent integrity. MAChR and VAChT
      results were compared with neuronal cell counts to assess their relations to
      local neuronal losses. RESULTS: Reduced MAChR binding-site density was
      demonstrated throughout the HF in the epilepsy specimens compared with autopsy
      controls and correlated in severity with reductions in cell counts in several HF
      regions. In contrast to MAChR, VAChT binding-site density was unchanged in the
      epilepsy specimens compared with autopsy controls. CONCLUSIONS: Reduction in
      MAChR binding in HS is attributable to intrinsic neuronal losses. Sparing of
      afferent septal cholinergic terminals is consistent with the hypothesis that an
      excitotoxic mechanism may contribute to the development of HS and refractory
      partial epilepsy in humans.

PMID- 9924901
TI  - Familial epilepsy with unilateral and bilateral malformations of cortical
      development.
AB  - PURPOSE: To describe a family in whom two sisters with epilepsy, mental
      retardation, and microcephaly had different malformations of cortical development
      detected by magnetic resonance imaging (MRI). METHODS: Clinical investigation of
      the patients and their family. High-resolution MRI, cognitive testing, and
      repeated EEG recording in both patients. RESULTS: In one patient, the
      malformation was bilateral and diffuse but much more pronounced in the parietal
      and occipital regions, with MRI characteristics indicating pachygyria
      polymicrogyria. In the other patient, the abnormality involved the right
      hemisphere, predominating around the perisylvian region, with MRI more clearly
      indicative of polymicrogyria. A brother also had severe epilepsy, diffuse EEG
      abnormalities, mental retardation, and microcephaly, but could not be studied
      neuroradiologically. CONCLUSIONS: Lack of MRI studies in the parents and brother
      does not allow a precise hypothesis on the mode of transmission. However,
      findings from this family indicate that unilateral malformations of cortical
      development detected during investigations after seizure onset may be genetically
      based, suggesting that a single genetic abnormality could be responsible for
      bilateral or unilateral malformations.

PMID- 9924902
TI  - Visual and quantitative ictal EEG predictors of outcome after temporal lobectomy.
AB  - PURPOSE: We investigated whether visual and quantitative ictal EEG analysis could
      predict surgical outcome after anteromesial temporal lobectomy (AMTL) in which
      mesial structures, basal, and temporal tip cortex were resected. METHODS: We
      retrospectively reviewed 282 presurgical scalp-recorded ictal EEGs (21- to 27
      channel) from 75 patients who underwent AMTL. We examined the pattern of seizure
      onset (frequency, distribution, and evolution) and estimated the principal
      underlying cerebral generators by using a multiple fixed dipole model that
      decomposes temporal lobe activity into four sublobar sources (Focus 1.1). We
      correlated findings with a 2-year postoperative outcome. RESULTS: Sixteen
      patients had seizures with a well-lateralized, regular 5 to 9-Hz rhythm at onset,
      that most often had a temporal or subtemporal distribution. All patients became
      seizure free after surgery. In 51 patients, seizure onset was remarkable for
      lateralized slow rhythms (<5 Hz), which sometimes appeared as periodic
      discharges, were often irregular and stable only for short periods (<5 s), and
      had a widespread lateral temporal distribution. Among these a favorable surgical
      outcome was encountered in patients with seizures having prominent anterior-tip
      sources ( 16 of 17 seizure free), whereas those with dominant lateral or oblique
      sources had a less favorable outcome (three of 14 and 13 of 18, respectively).
      Irregular, nonlateralized slowing characterized seizure onsets in eight patients.
      Three patients became seizure free after surgery. CONCLUSIONS: Both visual and
      quantitative sublobar source analysis of scalp ictal EEG can predict surgical
      outcome in most cases after AMTL and complement non-invasive presurgical
      evaluation.

PMID- 9924903
TI  - Improvement and deterioration of seizure control during the postsurgical course
      of epilepsy surgery patients.
AB  - PURPOSE: To determine the factors associated with changes in seizure control
      during the postsurgical course of epilepsy surgery patients. METHODS: Evaluation
      of patients after consecutive temporal and frontal resection whose seizure
      frequency was scored for each year of postsurgical follow-up. In each cohort,
      patients with a change in their seizure control after the first postsurgical year
      were compared with control subjects to determine factors that may be responsible
      for the change. RESULTS: Thirty-three (15%) of 214 temporal lobectomy versus 12
      (20%) of 59 frontal resection patients experienced a change in seizure control
      (p>0.05). Ten (5%) of 214 temporal lobectomy versus nine (15%) of 59 frontal
      resection patients experienced an improvement in seizure control (p = 0.009), but
      23 (11%) of 214 temporal lobectomy versus three (5%) of 59 frontal resection
      patients had a worsening in seizure control (p>0.05). In temporal lobectomy
      patients, preoperative unilateral temporal epileptiform discharges were
      associated with improvement (p = 0.03), whereas older age at surgery was
      associated with worsening of seizure control (p = 0.007). In frontal resection
      patients, presence of a congenital central nervous system (CNS) anomaly was
      associated with late improvement in seizure control (p = 0.006). CONCLUSION:
      During the postsurgical course, an improvement in seizure control is more common
      after frontal resection than after temporal lobectomy. Factors associated with
      improvement are the presence of a congenital CNS abnormality in frontal resection
      patients, and the occurrence of preoperative unilateral epileptiform discharges
      in temporal lobectomy patients. Older age at temporal lobectomy may be associated
      with greater risk of worsening seizure control.

PMID- 9924904
TI  - Lamotrigine concentrations in human serum, brain tissue, and tumor tissue.
AB  - PURPOSE: Although lamotrigine (LTG) has been used for years as an antiepilepic
      drug (AED), there are no data on penetration into the brain with the exception of
      a single case report. It was our aim to determine the LTG content in the brain
      and the tumor tissue and to bring the same into relation to the serum
      concentration and protein binding in neurosurgically operated patients. METHODS:
      Neurosurgical intervention was performed on 11 patients with brain tumors. Tumor
      tissue was removed, and LTG kinetics was carried out for 12 h. LTG was determined
      by means of (HPLC) and the protein binding by means of ultrafiltration. RESULTS:
      At the time of the section of the tumor, the LTG concentrations in the serum were
      an average of 3.7 microg/ml (range, 1.1-9.8); in the brain, an average of 6.8
      microg/g (range, 1.0-14.9); and in the tumor, an average of 4.4 microg/g (range,
      2.0-8.3). Brain/serum and tumor/serum ratios of 2.8 and 1.9, respectively, result
      from these data. The protein binding was on average 68% (range, 46-96).
      CONCLUSIONS: LTG is a lipophile AED with a moderate protein binding that
      penetrates brain tissue well and can be proven even in the tumor tissue.

PMID- 9924905
TI  - Dose-Response Study of Vigabatrin as add-on therapy in patients with uncontrolled
      complex partial seizures.
AB  - PURPOSE: This placebo-controlled, randomized, double-blind, multicenter study
      examined the efficacy and safety of three daily doses of vigabatrin (VGB; 1, 3,
      or 6 g) as add-on therapy in 174 patients with previously uncontrolled complex
      partial seizures with or without secondary generalization. METHODS: A 12-week
      pretreatment assessment period was followed by drug therapy with a 6-week
      titration period and a 12-week maintenance phase. RESULTS: VGB doses of 3 and 6
      g/day reduced median monthly frequency of seizures by 4.3 and 4.5 seizures,
      respectively, compared with 0.2 seizures for placebo (p = 0.0001). The
      percentages of patients classified as therapeutic successes (> or =50% reduction
      in seizure frequency) were 7% for placebo and 24, 51, and 54% for patients taking
      daily VGB doses of 1, 3, and 6 g, respectively; the comparison with placebo was
      significant for all treatment groups. The linear trend for dose response was
      highly significant (p< or =0.0001) for both median monthly seizure frequency and
      therapeutic success. Vigabatrin was well tolerated, causing no clinically
      significant changes in laboratory parameters, brain magnetic resonance imaging,
      evoked potentials, cognitive function, or psychosocial tests. Fatigue,
      drowsiness, and dizziness were the most common treatment-related adverse events
      in all treatment groups. Dropouts due to adverse events were higher in the 6
      g/day group. CONCLUSIONS: VGB was significantly more effective than placebo as
      add-on therapy in reducing seizure frequency. VGB at 3 and 6 g/day produced the
      best efficacy: however, adverse events may limit the use of the 6-g/day dose in
      some patients.

PMID- 9924906
TI  - Psychosis after resection of ganglioglioma or DNET: evidence for an association.
AB  - PURPOSE: David Taylor and Murray Falconer suggested that some patients may
      develop a psychotic illness after resection of a ganglioglioma that led to
      intractable seizures. They implied that the mechanism of this association
      remained unclear. This concept is currently not universally accepted (M. Trimble,
      personal communication). METHODS: We studied six children or young adults from
      four centers who developed psychosis after resection of a ganglioglioma or
      dysembryoplastic neuroepithelioma (DNET). RESULTS: All patients were operated on
      because of intractable epilepsy. The lesions involved mainly the temporal lobe.
      Patients had good outcomes for seizure control. In none of the six was
      potentially psychogenic medication used nor were the psychotic symptoms postictal
      in nature. The psychosis was schizophreniform with paranoid features and
      prominent depressive symptoms. Although some behavioral abnormalities were
      described preoperatively, none had been psychotic before operation. This type of
      psychotic reaction was not encountered in the four centers in a comparable period
      after resection of other types of lesions. This complication is rare; it occurred
      in only one of 39 patients who had such a lesion resected. CONCLUSIONS: Psychotic
      illness may rarely occur after resection of a ganglioglioma or DNET for treatment
      of intractable epilepsy. This does not seem to occur after removal of other types
      of lesions. Because the patients had good outcomes for seizures, the mechanism
      may be related to "forced normalization." The original observations of Taylor and
      Falconer are confirmed by this study; the reasons for the selective occurrence,
      however, remain speculative.

PMID- 9924908
TI  - Cross-cultural adaptation and use of the epilepsy psychosocial effects scale:
      comparison between the psychosocial effects of chronic epilepsy in Sweden and the
      United Kingdom.
AB  - PURPOSE: To establish Swedish weightings for the Epilepsy Psycho-Social Effects
      Scale (EPSES) and examine differences between Sweden and the U.K. in attitudes
      toward chronic epilepsy. METHODS: After translation and back-translation of the
      EPSES into Swedish, weightings were established through a paired comparison study
      in which 24 epilepsy professionals participated. The EPSES was then given to a
      hospital-based sample of 57 patients with chronic epilepsy and the results
      compared with a British sample matched for age, sex, and frequency of seizures.
      RESULTS: In the professional judgments of the EPSES statements, there were
      statistically significant differences in only four of 42 statements. Attitudes to
      employment, to medication, and to fear of seizures were considered more serious
      in the U.K., whereas social isolation was considered more a problem in Sweden.
      Patient attitudes to chronic epilepsy were found to be largely similar in the
      U.K. and Sweden; however, attitudes to employment, to the future, and to fear of
      seizures were significantly more a problem for patients in the U.K. CONCLUSIONS:
      The results indicate a great similarity in the interpretation of problems as
      measured by the EPSES in the U.K. and in Sweden. The differences in attitudes
      found are discussed in relation to economic and legislative differences between
      the two countries. Social as well as cultural differences should be taken into
      account when using standardized questionnaires. It is suggested that culturally
      specific weightings should be calculated and that these should be reevaluated at
      regular intervals.

PMID- 9924907
TI  - Autosomal dominant nocturnal frontal lobe epilepsy: an electroclinical study of a
      Norwegian family with ten affected members.
AB  - PURPOSE: The aim of the study was to describe in detail the electroclinical
      findings associated with a mutation in the acetylcholine receptor in a Norwegian
      family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
      Furthermore, we compared the clinical features associated with this mutation with
      those of an Australian family with a different mutation at the same locus, as
      well as with those of eight Italian families with ADNFLE and without a verified
      mutation in this gene. METHODS: We obtained medical records from all of the 10
      known affected members of the Norwegian family. A personal interview and a
      clinical neurologic examination were carried out in six of them. Interictal and
      ictal scalp EEG recordings were obtained in eight and three, respectively,
      computed tomography/magnetic resonance imaging (CT/MRI) in five, and blood
      samples for genetic analysis in seven individuals. The clinical features after an
      insertion of a leucine residue in the alpha4 subunit of the neuronal nicotinic
      acetylcholine receptor are examined. Furthermore, the clinical features that
      accompany this insertion and the clinical features associated with a missense
      mutation (Ser248Phe) in the same gene were compared. RESULTS: All the affected
      individuals had a seizure semiology consistent with frontal lobe seizures. Their
      seizures started in childhood (mean age, 8 years) and were often misinterpreted
      as benign nocturnal parasomnias, nocturnal paroxysmal dystonia, or a psychiatric
      disorder. The affected family members were of normal intellect and showed no
      abnormalities at neurologic and neuroradiologic examinations. Interictal scalp
      EEG registrations were mostly normal, ictal scalp EEG registrations in three
      individuals revealed left frontal low-voltage epileptiform discharges in two, and
      only shallow arousal preceding the attack in one. Although the seizure
      susceptibility varied among the affected individuals, the epilepsy course was
      mostly benign. CONCLUSIONS: Patients with ADNFLE, either with the 776ins3
      mutation or the Ser248Phe mutation, and those without any recognized mutation in
      the acetylcholine receptor, have strikingly homogeneous phenotypes, and it seems
      difficult to separate them on clinical grounds.

PMID- 9924909
TI  - Telephone validation of the Quality of Life in Epilepsy Inventory-89 (QOLIE-89).
AB  - PURPOSE: To assess the psychometric properties of the Quality of Life in Epilepsy
      Inventory-89 (QOLIE-89) administered via telephone and to compare these
      properties with data gathered through self-administration. METHODS: A study of
      139 patients with epilepsy was undertaken at three clinical sites in the United
      States. Patients participated in both telephone interview (T) and self
      administration (S). Order effect was controlled through randomization (T-S and S
      T). Twenty-eight S-T subjects participated in an assessment of the 2-week
      reproducibility of telephone interviews. RESULTS: Internal consistency and test
      retest reliability levels of the QOLIE-89 overall score were very high across
      method of administration (T = 0.98; S = 0.98; ICC of T = 0.96). Scores were
      significantly related to mood (Profile of Mood States, r = -0.76, for both
      methods, p<0.001) and two indicators of epilepsy severity (seizure frequency in
      the past month, T: r = 0.52, p<0.0001; S: r = 0.54, p<0.0001; days since last
      seizure, T: r = 0.28, p<0.001; S: r = 0.25, p<0.01), with no significant
      differences in coefficients by method of administration. Performance of the
      measure was consistent for patients with unimpaired and impaired memory, using
      the Rivermead Behavioural Memory Test, and across level of education.
      CONCLUSIONS: Results of this study indicate telephone interview is a viable
      option for evaluating HRQL in persons with epilepsy and support the reliability
      and validity of the QOLIE-89 regardless of method of administration.

PMID- 9924910
TI  - Violence and epilepsy: a close relation between violence and postictal psychosis.
AB  - PURPOSE: We investigated the incidence of well-directed violent behavior and
      suicide attempts in patients with temporal lobe epilepsy, with special attention
      to postictal psychosis. METHODS: We compared 57 episodes of postictal psychosis
      with 62 episodes of acute interictal (or alternative) psychosis and with 134
      complex partial seizures. All patients were matched for age and for age at onset
      of seizures. RESULTS: The incidence of well-directed violent behavior against
      human beings was significantly higher (23%) during postictal psychotic episodes
      than during acute interictal episodes (5%) and postictal confusion (1%). Suicide
      attempts were also more frequent during postictal psychosis (7%) than during
      either acute interictal psychosis (2%) or postictal confusion (0%). CONCLUSIONS:
      Our study showed that well-directed violent and self-destructive behavior was not
      a feature of epileptic psychosis in general but a specific hallmark of postictal
      psychosis.

PMID- 9924911
TI  - Benign familial neonatal convulsions followed by benign epilepsy with
      centrotemporal spikes in two siblings.
AB  - PURPOSE: To report on sibling cases with benign familial neonatal convulsions
      (BFNC) followed by benign epilepsy with centrotemporal spikes (BECT). METHODS:
      Case histories and EEGs were obtained for the two siblings with neonatal and
      subsequent epileptic seizures in one pedigree with BFNC. RESULTS: The family
      included six affected cases of BFNC in two generations: the proband, the
      proband's mother and two sisters, and the proband's maternal uncle and his
      daughter. The proband developed a generalized tonic convulsion 2 days after birth
      with no apparent cause and normal interictal EEG, and experienced a total of 18
      episodes of tonic or clonic seizures or both by age 9 months. In the follow-up
      course, an EEG recording showed rolandic discharges at 2 years, and a sylvian
      seizure occurred at 4 years during sleep. On carbamazepine therapy, the last
      seizure was recorded at 9 years after a total of 11 episodes of sylvian seizures,
      with normal EEGs after 12 years. The proband's sister experienced nine episodes
      of brief tonic seizures between 7 and 9 days after birth, and also developed
      eight episodes of sylvian seizures from 4 to 7 years, with rolandic discharges on
      EEG until age 9 years. All of the family members had normal psychomotor
      development, with no neurologic sequelae. CONCLUSIONS: This report of BFNC
      followed by BECT in sibling cases is significant in view of the genetic analysis
      and the classification of epilepsies and epileptic syndromes.

PMID- 9924912
TI  - Spitting automatism in complex partial seizures: a nondominant temporal
      localizing sign?
AB  - PURPOSE: Spitting as an ictal automatism has been rarely reported. We aimed to
      establish its potential lateralizing and localizing significance. METHODS: Review
      of patients undergoing surgery for intractable epilepsy at two comprehensive
      epilepsy centers. RESULTS: Five patients were found who had spitting as a
      stereotyped automatism of their complex partial seizures. All had evidence of
      right temporal ictal onset and underwent resective surgery. Two had tumors; one,
      a cavernous angioma; one, hippocampal gliosis, and one, hippocampal sclerosis. We
      found no instances of ictal spitting in patients with left hemisphere onset.
      CONCLUSIONS: Spitting as an automatism in complex partial seizures, although
      uncommon, may be a localizing sign to the nondominant temporal lobe.

PMID- 9924913
TI  - Lack of association between juvenile myoclonic epilepsy and HLA-DR13.
AB  - PURPOSE: We sought to replicate and extend a previously reported positive
      association between juvenile myoclonic epilepsy and HLA-DR13. METHODS: Ninety
      three subjects with juvenile myoclonic epilepsy and 93 normal blood donors,
      entirely of white origin with their families mostly of French extraction,
      underwent DNA-based HLA-DR13 and DQB6 typing. RESULTS: None of the investigated
      alleles or combination of alleles (DRB1*1301-DQB1*0603 or DRB1*1302-DQB1*0604)
      showed a significant difference between patients and controls. CONCLUSIONS:
      Unlike previously reported positive association, in this population, there is no
      evidence that susceptibility to juvenile myoclonic epilepsy is associated with
      HLA-DR13.

PMID- 9924914
TI  - It's time to revise the definition of status epilepticus.

PMID- 9924915
TI  - The revised operational definition of generalised tonic-clonic (TC) status
      epilepticus in adults.

PMID- 9924916
TI  - Riding on a carousel with IFN-alpha and TNF-alpha.

PMID- 9924917
TI  - Understanding uveitis through the eyes of a horse: relevance of models of ocular
      inflammation to human disease.

PMID- 9924918
TI  - Effect of type I interferon on experimental autoimmune uveoretinitis in rats.
AB  - In order to establish a scientific basis for the potential use of type I
      interferons (IFNs) in clinical uveitis, we examined the effect of a preparation
      of IFN-alpha/beta on experimental autoimmune uveoretinitis (EAU). Lewis rats were
      immunized with bovine interphotoreceptor retinoid-binding protein (IRBP) and
      given daily intramuscular injections of 10(5) IU mouse natural IFN-alpha/beta.
      Intraocular inflammation was assessed by slit-lamp biomicroscopy and
      histopathological examination. Rats treated daily with IFN-alpha/beta starting on
      the day of IRBP immunization showed decreased intraocular inflammation as well as
      a slight delay in onset of inflammation when compared to control rats. This
      effect was also observed to a lesser extent in rats treated during either the
      induction phase of EAU only, or starting immediately after the onset of
      inflammation in the effector phase of EAU. Measurement of IRBP-stimulated
      splenocyte proliferation and serum anti-IRBP antibody subtypes did not reveal a
      significant difference between IFN-alpha/beta-treated rats and control rats.
      Measurement of cytokine production by IRBP-stimulated splenocytes in vitro showed
      significantly decreased TNF-alpha for IFN-alpha/beta-treated rats compared to
      control, but no difference for IFN-gamma, IL-2, IL-4, and IL-10. These results
      indicate that systemic administration of IFN-alpha/beta suppresses IRBP-induced
      EAU in rats, and suggest that such suppression may be mediated in part by a
      reduction in TNF-alpha production.

PMID- 9924919
TI  - Transient loss of prostaglandin synthetic capacity in rabbit iris-ciliary body
      following anterior chamber paracentesis.
AB  - The trauma-induced acute ocular inflammatory response has been characterized by
      investigating the kinetics of blood-aqueous barrier (BAB) breakdown,
      prostaglandin (PG) accumulation in the aqueous humor, and cyclooxygenase (PGH
      synthase) activity of the iris-ciliary body (ICB) following paracentesis in the
      NZA rabbit. BAB breakdown was assessed by quantifying plasma protein
      extravasation into the anterior chamber. PGE2 and 6-keto-PGF(1alpha)
      concentrations in the aqueous humor were quantified by radioimmunoassay. The
      capacity of ICB tissue homogenates to generate eicosanoids from exogenously
      supplied [I-14C]-arachidonic acid was assessed radiometrically by HPLC.
      Paracentesis resulted in a rapid and dramatic increase in aqueous humor PGE2
      concentrations. Within 10 minutes, PGE2 concentrations increased 937-fold, from
      6.2+/-4.9 pg/ml to maximal concentrations of 5810+/-3829 pg/ml. PG synthesis was
      followed temporally by an increase in aqueous humor protein, with peak levels
      (53.1 mg/ml) achieved within 30 minutes post paracentesis. Both PGE2 and protein
      levels gradually declined to near baseline levels 48 hours after trauma. ICB
      homogenates from naive animals produced significant amounts of eicosanoids (total
      PG=2.95 nmol/ 10 min/100 mg tissue). HHT (12 hydroxy-heptadecatrienoic acid) was
      produced in the greatest quantity, followed by PGE2alpha, PGI2, and TXB2/ PGF2 .
      Notably, following paracentesis, eicosanoid synthesis by the isolated ICB was
      observed to diminish abruptly. Formation of all eicosanoids was uniformly reduced
      by approximately 40% five minutes following paracentesis, with an 81% decrease in
      synthetic activity at 15 minutes. Eicosanoid synthetic capacity was only restored
      to baseline 48 hours post paracentesis. These findings suggest that, following
      ocular trauma, temporal changes occur in ICB PG synthetic activity that may
      impact on the selection of an optimal dosing paradigm for efficacy testing of
      topically administered NSAIDs.

PMID- 9924920
TI  - Retinal immunopathology in horses with uveitis.
AB  - BACKGROUND: Equine uveitis is a spontaneous disorder of horses that can serve as
      a model for the study of human uveitis. Although the initial presentation is that
      of an anterior uveitis, retinal involvement has been noted in some cases. We
      report here the immunohistopathology of retinas from horses with uveitis.
      METHODS: Sections of eyes recovered from horses with naturally occurring uveitis
      and from Shetland ponies with experimental leptospira-induced uveitis were
      stained by hematoxylin and eosin for histopathological evaluation.
      Immunohistochemistry was used to evaluate retinas for MHC Class II antigen
      expression and infiltration of T and B lymphocytes. RESULTS: Histopathological
      abnormalities in retinas from horses with uveitis ranged from minimal to total
      loss of retinal tissue. MHC Class II antigen-positive round and dendritiform
      cells were seen in these retinas, but were not seen in retinas from horses
      without uveitis. There was no significant reactivity noted in the retinal pigment
      epithelial cells or Muller cells. Numbers of MHC Class II antigen-expressing
      cells and T lymphocytes correlated with the extent of retinal histopathology. B
      lymphocytes were seen primarily in retinas from horses that were seroreactive for
      Leptospira interrogans serovar pomona. Retinas from ponies with experimental
      uveitis had changes similar to those from horses with spontaneous uveitis.
      CONCLUSIONS: These results suggest that retinal pathology may be a primary
      immunological event in equine uveitis, provide evidence that leptospira
      associated uveitis may be a distinct subset of equine uveitides, underscore the
      relevance of the study of equine uveitis to human uveitis, and support the
      plausibility of a post-infectious immunopathogenesis of some naturally occurring
      uveitides in both humans and horses.

PMID- 9924921
TI  - Ciliary body melanoma masquerading as chronic uveitis.
AB  - PURPOSE: To report a case of ciliary body melanoma that masqueraded as chronic
      uveitis. METHODS: A patient experienced persistent unilateral panuveitis and
      elevated intraocular pressure. Inflammation and pressure worsened after cataract
      extraction and lens implantation. Diagnostic vitrectomy was non-revealing.
      RESULTS: Repeat vitrectomy and lens implant removal revealed a ciliary body mass,
      suggestive of melanoma. Ultrasonography and clinical evaluation by the retinal
      oncologists supported this diagnosis. The uveitis persisted despite aggressive
      medical treatments, including methotrexate. Proton beam irradiation of the
      melanoma led to resolution of uveitis and restoration of normal intraocular
      pressure. CONCLUSION: Ciliary body melanoma can present as chronic uveitis and
      refractory glaucoma.

PMID- 9924922
TI  - Immune privilege in the retina.
AB  - As new Ag-specific and non-Ag-specific mechanisms contributing to ocular immune
      privilege are revealed, the relevance of old paradigms properly comes into
      question. My lab has a particular interest in the immune privilege of the retina.
      While the presence of active mechanisms of tolerance, such as immune deviation,
      is now well-established, we propose that sequestration provides the first line of
      immune privilege in the retina. When it fails, active, inducible mechanisms
      provide backup to protect the integrity of the retina and vision. Some of the
      observations that led to our hypotheses and their supporting experiments are
      discussed below.

PMID- 9924923
TI  - The clinico-ophthalmological spectrum of antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a hypercoagulable disorder with highly
      variable symptomatology including ocular manifestations. Antiphospholipid
      antibodies (aPL) are the serologic markers of this clinical entity. Our aim was
      to note the main associated ocular features of APS and elucidate which pathogenic
      mechanisms may participate. Retinal vascular thrombosis and different neuro
      ophthalmologic manifestations, such as optic neuropathy and amaurosis fugax, may
      be considered as the ocular hallmarks of this syndrome. Ocular features due to
      aPL-induced thrombosis should be treated with anticoagulant drugs. Conversely,
      for the treatment of ocular features due to immunological mechanisms such as
      vasculitis, immunosuppressive regimes seem to be more appropriate.

PMID- 9924924
TI  - Comparison of the cytotoxic effects of corticoids on the neoplastic B cells.
AB  - Many clinical trials have been engaged to prove the benefits of new drugs in the
      treatment of hematological tumours. However, no real progress have occurred in
      diseases such as multiple myeloma, the association of melphalan and prednisone is
      still the mainstay of the treatment. During all these years, the family of
      glucocorticoids have not been totally studied. Their efficiency in the cure of
      lymphoid malignancies has been early recognised, but still to be based on their
      anti-inflammatory potency for the dosages. Only few works reported the comparison
      between members of this family. We demonstrate in this work, in vitro, with a
      cell line of medium sensibility and a B cell of tumoral origin grew up in our
      laboratory, that exists some differences in the anti-neoplastic potency of the
      more commonly used corticoids. If the order in which we can class these drugs is
      not surprising and empirically known, the importance of the differences observed
      need a special attention. We also found that these drugs might have stimulatory
      effects, at various degree in function of their concentrations, on the
      proliferation of the B cell lines. Theses side effects coupled to the efficiency
      variations of each corticoid present the need of paying more attention to the
      choice of the molecule implied in the chemotherapy.

PMID- 9924925
TI  - Comparative analysis of class I, II and III epitope-detecting CD34 monoclonal
      antibodies by quantitative flow cytometry.
AB  - The aim of this study was to compare different CD34 monoclonal antibodies (MAbs)
      belonging to three different classes: MY10 class I, QBend10 class II, a mixture
      of three selected MAbs class I and II designated as CD34 Pool, and 8G12 class
      III. Bone marrow (BM) samples from 13 healthy donors were analyzed for: 1)
      percentage of CD34+ cells, 2) quantitative expression of CD34 epitopes (antigen's
      density - AgD) using a quantitative indirect immunofluorescence (QIFI) test, 3)
      study of CD34+ cell subsets defined by CD34 and CD38 coexpression. 8G12 MAb
      showed the highest reactivity with regard to the percentage of detected CD34+
      cells and AgD on these cells. A nearly identical percentage of CD34+ cells was
      detected with CD34 Pool, but with a lower AgD. With QBend10, the percentage of
      CD34 expressing cells was insignificantly decreased and the AgD was slightly
      lower. The expression of the MY10 epitope was the lowest and was detected on the
      lowest number of CD34+ cells. Concerning CD34 and CD38 coexpressing subset, we
      observed that 8G12 class III MAb detected CD34loCD38dim cells with comparable
      efficiency with MY10 class I MAb, but with significantly higher level than
      QBend10 class II and CD34 Pool class I+II MAbs. The CD34hiCD38dim subset was
      detected with the same efficiency by QBend10, CD34 Pool or 8G12 MAbs but with
      significantly higher frequency than MY10 MAb. IN CONCLUSION: class II and III
      MAbs appear preferable for flow cytometric quantification of CD34+ cells; for
      CD34+ cell subsets determination class III MAbs should be suitable.

PMID- 9924926
TI  - Early infectious complications after bone marrow transplantation requiring
      medical ICU admission.
AB  - The objective of this study was to define the type, the incidence and the outcome
      of early infectious complications (mean interval between day 1 post-BMT and the
      onset of fever was 9+/-3 days) occurring in granulocytopenic bone marrow
      transplant recipients, requiring medical intensive care unit admission. Over a
      five-years period, forty-one patients with microbiologically confirmed infection
      were enrolled, with a statistically significant higher frequency of allogeneic
      marrow transplant recipients (51%, p < 0.02). Infectious pneumonia occurred in 24
      patients (59%), septicemia with septic shock in ten patients (24%), catheter
      related infection in 5 patients (12%) and meningitis in 2 patients (5%) (p <
      0.001). Twenty-six patients died (63%). Among the patients with confirmed
      infectious pneumonitis, which occurred most frequently in allogeneic marrow
      recipients (p < 0.02), 16 died (67%). This poor outcome was related to the
      requirement of mechanical ventilation. Eight patients (80%) with septicemia and
      septic shock and the two patients with meningitis died. Bacteria (Pseudomonas
      aeruginosa and Staphylococcal species) were the most common isolated in
      bronchoalveolar lavage fluid and blood cultures. We found a lower incidence of
      fungal or viral infections compared to previous studies. Empiric antimicrobial
      therapy in the cases of patients admitted in ICU may be included antibiotics anti
      Pseudomonas and anti-Staphylococcus, as the ecology of hematology unit. The
      requirement of mechanical ventilation is the main adverse prognostic factor in
      transplanted patients. At ICU admission, patients with hepatic failure combined
      with respiratory failure represented a subgroup with a dismal prognosis.

PMID- 9924927
TI  - Leukemic pleural effusion in B-cell prolymphocytic leukemia.
AB  - The occurrence of leukemic pleural effusion is a rare complication in chronic
      lymphocytic leukemia and has not been reported in B-cell prolymphocytic leukemia
      (B-PLL). We report a case of pleural effusion revealing a B-PLL. The diagnosis
      was made on the cytological and immunological characteristics of cells in the
      blood and pleural effusion. This patient was treated with fludarabine and was in
      complete remission after three courses. This observation may have clinical
      implications for the use of new adenoside nucleotide analogues in symptomatic B
      PLL.

PMID- 9924928
TI  - A case report: CD8 expression in B-cell chronic lymphocytic leukemia (B-CLL).
      Prognostic significance of the aberrant CD8 expression.
AB  - The human CD8 molecule is usually expressed on T lymphocytes or natural killer
      cells but not on normal B cells. Over a course of 5 years, we followed a case of
      B-CLL which aberrantly expressed the CD8 molecule. During this period, the
      clinical and hematological conditions of the patient were stable. This B-CLL
      presented a typical immunophenotype (HLA DR+, CD19+, CD5+, CD23+) with monotypic
      expression of surface immunoglobulin light chain kappa. We confirmed the CD8
      expression on these leukemia cells by using double labelling and different
      antibodies directed against this antigen. We measured the quantitative expression
      of the CD8 molecule. The number of CD8 molecules per cell was clearly lower on
      these malignant B cells than on normal T lymphocytes. In order to evaluate the
      prognostic significance of this CD8 expression, we quantitated in parallel other
      markers such as CD5, CD23, CD22, CD11c. During 5 years, this aberrant CD8
      expression persisted and was associated with an increase of the CD23 and a
      decrease of CD22 levels, known to correlate with a good prognosis in agreement
      with the karyotype analysis. Altogether our results led us to conclude that the
      aberrant CD8 expression in this case of B-CLL may correlate with a non-aggressive
      form of lymphoproliferative disorder.

PMID- 9924929
TI  - Potential roles for focal adhesion kinase in development.
AB  - Focal adhesion kinase (pp125FAK or FAK) is a protein tyrosine kinase which is
      associated with intracellular signalling cascades which are initiated when the
      integrin family of cell adhesion molecules engage extracellular matrix molecules.
      In cultured cells, this molecule is physically associated with focal adhesions,
      which are well-defined regions of intimate cell-to-substratum adhesion. In this
      location, it interacts with other proteins of the focal adhesion to activate
      intracellular signalling events associated with cell adhesion. The in vitro
      expression of FAK and its level of phosphorylation appear to be related to
      several physiological phenomena, including cell spreading, cell differentiation,
      cell locomotion and cell death. Because these phenomena are all of critical
      importance during morphogenesis, and because FAK is expressed in embryonic cells,
      evidence has been accumulating to indicate that FAK may be an important modulator
      of developmental processes. In this review, this evidence is surveyed together
      with evidence from analogous situations, such as tumour cell migration and
      invasiveness. Although evidence suggesting a role for FAK in morphogenesis is
      accumulating, current uncertainties regarding its cytoplasmic location and its
      molecular interactions in vivo make it difficult to reach definitive conclusions
      regarding the significance of its contributions to developmental processes.

PMID- 9924930
TI  - Pallidal and cerebellar inputs to thalamocortical neurons projecting to the
      supplementary motor area in Macaca fuscata: a triple-labeling light microscopic
      study.
AB  - We investigated the interrelationship between the supplementary motor area (SMA)
      thalamocortical projection neurons and the pallidothalamic and cerebellothalamic
      territories in the monkey (Macaca fuscata) using a combination of three tracers
      in a triple labeling paradigm. Thalamic labeling was analyzed following
      injections of the anterograde tracers, biotinylated dextran amine (BDA) into the
      internal segment of the globus pallidus (GPi) and wheat germ agglutinin
      conjugated to horseradish peroxidase (WGA-HRP) into the contralateral cerebellar
      interpositus and dentate nuclei. In addition, the retrograde tracer cholera toxin
      subunit B (CTB) was injected into the physiologically identified hand/arm
      representation of SMA. The tissue was processed sequentially using different
      chromogens in order to visualize all three tracers in a single section. We found
      that the SMA thalamocortical neurons occupied a wide band extending from the
      ventral anterior nucleus pars principalis (VApc) through the ventral lateral
      nucleus pars oralis (VLo) and the ventral lateral nucleus pars medialis (VLm) and
      into to the ventral lateral nucleus pars caudalis (VLc) including a portion of
      ventral posterior lateral nucleus pars oralis (VPLo) and nucleus X. The heaviest
      CTB labeling was found in VLo with dense plexuses of BDA labeled pallidothalamic
      fibers and swellings often observed superimposed upon retrogradely labeled CTB
      cells. In addition, dense foci of cerebellothalamic WGA-HRP anterograde label
      were observed coinciding with the occasional retrogradely CTB labeled neurons in
      VLc and transitional zones between VApc, VLo and VPLo. Our light microscopic
      results suggest that the SMA receives thalamic inputs with afferents largely
      derived from GPi and minor inputs originating from the cerebellum.

PMID- 9924931
TI  - Morphology of the oocyte-follicular connection in the mare.
AB  - The present study characterised the oocyte-follicular connection (i.e., oocyte
      fixation site) in Graafian follicles of the mare morphologically. Antral
      follicles were dissected in toto from ovaries obtained from oestrous, dioestrous
      and transitional mares after slaughter. The location of the cumulus oophorus
      complex in relation to the ovulation fossa, the width and density of the blood
      vessels surrounding the cumulus oophorus complex, the relative dimensions and
      histological aspects of the cumulus oophorus were investigated. For
      ultrastructural analysis of the junctional regions, cumulus-oocyte complexes were
      recovered in vivo by transvaginal ultrasound-guided follicle aspiration. The
      location of the oocyte fixation site was independent of mare, follicular size and
      stage of the oestrous cycle. In 82% of follicles, the oocytes were embedded in a
      broad based cell mount. The width and density of the blood vessels surrounding
      the oocyte fixation site were correlated to each other, but independent of
      follicular size and cyclic stage. The histological appearance of the cumulus
      oophorus varied, especially in respect to the compactness, and loosening of the
      cumulus cell population was observed in several medium-sized follicles from
      dioestrous mares. Loosening of the cumulus cell population was apparently
      associated with decreased interdigitation between adjacent corona radiata cells.
      It can be concluded that the fixation site of the equine cumulus oophorus complex
      represents a firm cellular anchorage between follicular wall and oocyte.
      Furthermore, the location of the cumulus oophorus complex in relation to the
      ovulation fossa and characteristics of the surrounding blood vessels is
      independent of follicular size and cyclic stage.

PMID- 9924932
TI  - Cerebral and pial microvessels: differential expression of gamma-glutamyl
      transpeptidase and alkaline phosphatase.
AB  - Pial microvessels have several important blood-brain barrier (BBB)
      characteristics in common with cerebral microvessels, despite lacking their
      astrocytic ensheathment. We have therefore determined whether they have the same
      distribution of two enzymes, gamma-glutamyl transpeptidase (GGTP) and alkaline
      phosphatase, both of which are known to be astrocyte-dependent. GGTP was absent
      from all rat pial microvessels but strongly present in brain cortical
      capillaries. Alkaline phosphatase was heterogeneously expressed in pial
      microvessels, including capillaries, but strongly positive in brain cortical
      capillaries. Diffusible, inductive factors produced by astrocytes could account
      for these differences in enzyme distribution between the two vessel types.
      Furthermore, differences in expression between the two markers may reflect their
      differing sensitivities to the astrocytic factors. Caution is urged in the common
      usage of the pial microvessel as a model system in BBB studies.

PMID- 9924933
TI  - Serotonergic neurons and processes in the adult and developing retina of
      Ichthyophis kohtaoensis (Amphibia; Gymnophiona).
AB  - Ichthyophis kohtaoensis is a tropical, limbless amphibian species with extremely
      small eyes (540 microm in adults). Adapted to a subterranean, burrowing mode of
      life, orientation and prey capture are predominantly guided by olfaction. The
      only visually guided behavior seems to be negative phototaxis. As
      electrophysiological single cell recordings have so far failed,
      immunohistochemical transmitter studies are a starting-point for a functional
      investigation of the visual system of this group of amphibians. In the present
      study, the organization and development of the serotonergic system have been
      examined in the retinae of embryonic, larval and adult I. kohtaoensis, using an
      antiserum against serotonin. Labeled somata are situated in the inner nuclear
      layer, presumably representing amacrine cells, and in the ganglion cell layer.
      However, some immunoreactive cells are located in the middle of the inner nuclear
      layer that send processes to both plexiform layers, probably representing bipolar
      cells. An additional type of immunoreactive soma, situated in the inner plexiform
      layer, have been found only in retinae of embryonic stages. Varicose serotonergic
      fibers form a diffuse plexus that covers the whole inner plexiform layer.
      Immunolabeled fibers can occasionally be demonstrated in the optic nerve head.
      During retinal development, the distribution and number of transmitter-expressing
      cells changes but no general reduction of the visual system is detectable. Adult
      stages still have a serotonergic system comparable to amphibians with a well
      developed visually guided behavior indicating that the eyes of I. kohtaoensis
      although being of minor importance in a subterranean habitat, retain all the
      elements of functioning sense organs.

PMID- 9924934
TI  - Versican in human fetal skin development.
AB  - The extracellular matrix of human fetal skin differs substantially from that of
      adult skin. Fetal skin contains sparse amounts of fibrillar collagen enmeshed in
      a highly hydrated amorphous matrix composed of hyaluronan and sulfated
      proteoglycans. Both fetal and adult skin contain two major interstitial
      proteoglycans that are extracted by chaotrophic agents and detergents. These are
      the large chondroitin sulfate proteoglycan versican and the small dermatan
      sulfate proteoglycan decorin. For this study, proteoglycans extracted from fetal
      and adult skin were compared on Western blots to determine the relative amounts
      of versican. Decorin present in the same samples provided an internal standard
      for these studies. Fetal skin differed from adult skin in that it contained a
      significantly higher proportion of versican than did adult skin.
      Immunohistochemical studies compared early-fetal with mid-fetal skin and found
      that versican was a significant component of the interstitial extracellular
      matrix at both of these stages of skin development. However, by the mid-fetal
      period, interstitial versican became restricted to the upper half of the dermis,
      although versican also continued to be highly expressed around hair follicles,
      glands, and vasculature in the lower half of the dermis. Fetal skin extracts
      differed from an adult skin extract by the presence of a 66-kDa protein
      immunologically related to versican and by the absence of a 17-kDa core protein
      of a proteoglycan related to decorin. Both of these molecular species may
      represent degradation products of their respective proteoglycans. Monoclonal
      antibodies which detect epitopes in native chondroitin sulfate glycosaminoglycan
      chains recognized versican extracted from fetal skin. However, the tissue
      distribution of these antigens did not entirely conform to that for versican core
      protein, suggesting that versican in different regions of the skin may be
      substituted with glycosaminoglycan chains with different microchemistries. The
      results of these studies indicate that human fetal skin is structurally different
      from adult skin in terms of both the distribution and the composition of the
      large, aggregating chondroitin sulfate proteoglycan versican.

PMID- 9924935
TI  - Comparison of enteric neuronal morphology as demonstrated by Dil-tracing under
      different tissue-handling conditions.
AB  - The aim of this study was to determine locations and morphologies of enteric
      neurons innervating the small intestinal mucosa of the pig after application of
      the carbocyanine tracer Dil onto a single villus. The tissue was processed in two
      ways: incubation (1) of fixed material (postmortem tracing) for several months
      and (2) of living specimens within organotypic culture in vitro for several days
      (supravital tracing). In both procedures Dil-labelled neurons were found in the
      three ganglionated plexuses, the internal and external submucous plexus as well
      as the myenteric plexus. Postmortem tracing revealed different neuronal
      morphologies. Adendritic type II neurons were present in all three plexuses, type
      IV neurons with short, scarcely branched, polarly emerging dendrites were mainly
      found in the myenteric plexus and small dendritic neurons were mainly present in
      the internal submucous plexus. The latter may correspond to minineurons hitherto
      described only immunohistochemically. Tracing within tissue culture showed somata
      of neurons and, partly, proximal segments of processes to be labelled. Subsequent
      immunohistochemistry using general neuronal markers revealed some neurons to be
      adendritic type II neurons. Visualization of dendrites was less clear, hampering
      an accurate morphological classification of dendritic neurons. Our results
      suggest that neurons of all ganglionated enteric nerve plexuses of the pig
      participate in the innervation of the mucosa, and that postmortem tracing
      revealed enteric neuronal morphology more clearly than supravital tracing. Since
      the former method cannot be applied for deciphering the chemical coding of
      enteric neurons, combination of both methods will extend our knowledge of the
      morphological substrate for the intrinsic neuronal microcircuits in the
      gastrointestinal tract.

PMID- 9924936
TI  - The development of the endotheliochorial mink placenta: light microscopy and
      scanning electron microscopical morphometry of maternal vascular casts.
AB  - The development of the mink endotheliochorial placenta has been studied by means
      of light microscopy and scanning electron microscopy of maternal vascular
      corrosion casts. The placental blood vessels of three groups of mink,
      representing early, intermediate and near-term gestational ages were either
      perfusion fixed for histology, or instilled with liquid plastic in order to
      prepare vascular casts, which were examined qualitatively and/or quantitatively.
      The maternal component of the placental vascular system evolves from
      preimplantation blood vessels between the endometrial glands, into which the
      initial feto-maternal contact is made. The influence of highly invasive
      syncytiotrophoblast provokes a transition of the maternal capillaries into
      extensively anastomosing sinusoids with a subsequent modification of their
      endothelial cells into large cells with luminal protrusions. Three-dimensionally,
      the sinusoids are arranged as vascular crypts. This implies a villous-crypt type
      of interdigitation for the mink, but since the fetal capillaries surround the
      maternal sinusoids as a dense network a labyrinth is formed. The vascular crypts
      are supplied by very short arterioles, branching from maternal stem arteries,
      which arise from branches of the uterine artery and move straight to the surface
      of the endometrium. Venous outlets of the sinusoids converge onto venules and
      large stem veins in the deepest portion of the endometrium. This architectural
      pattern persists until term. Morphometry was used to confirm the qualitative
      observations in vascular casts. The diameter of maternal vascular crypts
      significantly increased from 137.3+/-21.9 microm in early gestation up to 217.8+/
      80.9 microm in the intermediate stage and 431.8+/-119.5 microm near-term, when
      compared to the paraplacental zone in early gestation (82.2+/-19.5 microm). The
      capillary or sinusoidal diameter also increased significantly from intermediate
      stage (42.9+/-11.8 microm) to near term (60.1+/-16.7 microm), whereas the
      difference in the paraplacental zone (7.3+/-2.1 microm) and early gestation
      (13.0+/-3.2 microm) was not statistically significant.

PMID- 9924937
TI  - Immunoreactivity for calcium-binding proteins in the claustrum of the monkey.
AB  - The claustrum is topographically and reciprocally connected with many different
      cortical areas, and anatomical and physiological data suggest it is composed of
      functionally distinct subdivisions. We asked if the distribution of cells
      immunoreactive for three calcium-binding proteins, parvalbumin, calbindin D-28k
      and calretinin would delineate functional subdivisions in the claustrum. We also
      asked if, as in cortex, different cell types were immunoreactive for the
      different proteins. We found that cells with parvalbumin-ir were large,
      multipolar cells. Cells immunoreactive for calretinin were bipolar cells with
      elongated cell bodies and beaded dendrites. There were three different types of
      cells immunoreactive for calbindin. The most numerous were small cells with round
      or oval cell bodies and numerous fine, winding processes. A second type were
      large multipolar, cells that resembled the parvalbumin-ir cells. The third class
      were bipolar cells with large, elongated cell bodies. Each type of cell resembles
      a cell type described in earlier Golgi studies, and each has a morphological
      cortical counterpart. While the different cell types varied in density, each was
      seen over the anterior-posterior and dorsal-ventral extent of the claustrum.

PMID- 9924938
TI  - Tension and bending, but not compression alone determine the functional
      adaptation of subchondral bone in incongruous joints.
AB  - In the present study, we tested the hypothesis that tension and bending, rather
      than compression alone, determine the functional adaptation of subchondral bone
      in incongruous joints. We investigated whether tensile stresses in the
      subchondral bone of the humero-ulnar articulation are affected by the direction
      of muscle and joint forces, and whether the tensile stresses are large enough to
      cause microstructural adaptation, specifically a preferential alignment of the
      trabeculae and the subchondral collagen fibres. Using a previously validated
      finite element model of the human humero-ulnar joint, we calculated the contact
      pressure, the principal compressive and tensile stresses, and the strain energy
      density in the subchondral bone for various flexion angles. A bicentric (ventro
      dorsal) pressure distribution was found in the joint at 30 degrees to 120 degrees
      of flexion, with contact pressures of up to between 2.5 and 3 MPa in the ventral
      and dorsal aspects of the ulnar joint surface, but less than 0.5 MPa in the
      centre. The principal tensile stress in the subchondral bone of the trochlear
      notch quantitatively exceeded the principal compressive stress at low flexion
      angles (maximum 8.2 MPa), and the distribution of subchondral strain energy
      density differed substantially from that of the contact stress (r=-0.72 at 30
      degrees and r=+0.58 at 90 degrees of flexion). No important tensile stress was
      computed in the trochlea humeri. On contact radiography, we found sagittally
      orientated subarticular trabeculae in the notch, running tangential to the
      surface. Furthermore, we observed sagittally orientated split lines in the
      subchondral bone of the notch of 20 cadaver joints, suggesting a ventro-dorsal
      orientation of the collagen fibres. The trochlea humeri, on the other hand, did
      not show a preferential direction of the subchondral split lines, these findings
      confirming the predictions of tensile stresses in the model. We conclude that,
      due to the important contribution of tension to subchondral bone stress, the
      distribution of subchondral density cannot be directly employed for assessing the
      long term distribution of joint pressure at the cartilage surface. The magnitude
      of the tensional stress varies considerably with the direction of the muscle and
      joint forces, and it appears large enough to cause functional adaptation of the
      subchondral bone on a microstructural level.

PMID- 9924939
TI  - Characterization of lactococci isolated from minimally processed fresh fruit and
      vegetables.
AB  - Lactic acid bacteria isolated from minimally processed fresh fruit and vegetable
      products were identified as Lactococcus lactis subsp. lactis on the basis of
      phenotypic tests, presence of lactococcal IS elements, and partial sequence
      analysis of the 16S rRNA gene. Isolated bacteria were differentiated using pulsed
      field gel electrophoresis of SmaI digests of genomic DNA. Sprouted seeds were the
      best source of strains, and lactococci appear to be the dominant microflora on
      these products during the period they are intended to be eaten. Although these
      plant strains showed many similarities to strains of L. lactis used as dairy
      starter cultures, their carbohydrate fermentation patterns were unusual and
      probably reflect their environmental origin. Most strains fermented sucrose and
      xylose, and some also fermented raffinose and melibiose. Most of the bacteriocin
      producing strains produced nisin, and nisin genes could also be detected in
      strains that showed no bacteriocin activity, or that produced a different
      bacteriocin with a narrow spectrum of activity. One strain produced nisin but was
      unable to ferment sucrose, properties that have been generally regarded as
      linked. These strains may have uses as biopreservatives for minimally processed
      plant products.

PMID- 9924940
TI  - Detection of pathogenic Yersinia enterocolitica in enrichment media and pork by a
      multiplex PCR: a study of sample preparation and PCR-inhibitory components.
AB  - A multiplex PCR assay including sample preparation was developed to detect viable
      pathogenic strains of Yersinia enterocolitica in PCR-inhibitory samples, such as
      pork and enrichment media. The method developed was used to simultaneously detect
      the plasmid-borne virulence gene yadA and a Yersinia-specific region of the 16S
      rRNA gene. According to an auto-agglutination test for virulence-plasmid-bearing
      strains of Y. enterocolitica, all potential pathogenic strains tested were
      detected by the assay. A DNA extraction procedure, an aqueous two-phase system
      composed of polyethylene glycol 4000 and dextran 40 and a buoyant density
      centrifugation method, based on Percoll, were compared with regard to their
      efficiency in separating Yersinia enterocolitica from PCR inhibitors originating
      from enrichment media and pork. Using the density gradient centrifugation method
      resulted in a detection level of 4.0 x 10(2) CFU Y. enterocolitica per ml
      enrichment media. To ensure detection of viable bacteria a short enrichment step
      was included in the sample preparation together with the density gradient
      centrifugation. When this sample treatment method was evaluated with a selective
      enrichment medium together with a background flora inoculated with approximately
      1.0 x 10(1) CFU per ml of Y. enterocolitica and incubated at 25 degrees C, a
      positive PCR result was obtained after 6 to 8 h. Our results indicate that
      selective enrichment followed by buoyant density gradient centrifugation provides
      a convenient and user-friendly sample preparation method prior to PCR.

PMID- 9924941
TI  - Colonisation and competitiveness of Aspergillus and Penicillium species on maize
      grain in the presence of Fusarium moniliforme and Fusarium proliferatum.
AB  - The effects of different steady-state water activity levels (a(w), 0.93, 0.95 and
      0.98) and temperature (15 and 25 degrees C) on colonisation patterns of
      Aspergillus and Penicillium spp., when colonising irradiated maize grain in the
      presence of Fusarium moniliforme and Fusarium proliferatum were assayed in terms
      of populations (colony forming units, CFUs g grain(-1)), seed infection and
      colonisation rates. The activity of F. moniliforme and F. proliferatum in grain
      reduced the presence of Aspergillus flavus, Aspergillus niger, Aspergillus
      ochraceus to some extent, particularly at 15 degrees C and higher water
      availabilities (0.95-0.98 a(w)). In contrast, colonisation patterns of
      Penicillium implicatum on maize grain were unaffected by either Fusarium spp. in
      terms of CFUs or seed infection. Correlations were made between CFUs, seed
      infection, growth rates and niche overlap indices and hyphal interactions to try
      and link key indicators of competitiveness and dominance by an individual
      species.

PMID- 9924942
TI  - Detection of beer spoilage bacteria Megasphaera and Pectinatus by polymerase
      chain reaction and colorimetric microplate hybridization.
AB  - Anaerobic bacteria of the genera Megasphaera and Pectinatus cause beer spoilage
      by producing off flavours and turbidity. Detection of these organisms is
      complicated by the strict anaerobic conditions and lengthy incubation times
      required for their cultivation, consequently there is a need for more rapid
      detection methods. A polymerase chain reaction (PCR) method and a colorimetric
      microplate hybridization assay were developed for the rapid and specific
      detection of Megasphaera cerevisiae and Pectinatus spp. A biotinylated primer
      pair was designed for the amplification of a 403 base pair (bp) fragment of the
      M. cerevisiae 16S rRNA gene and a primer pair from literature was used for the
      amplification of an 816 bp fragment of Pectinatus 16S rRNA gene. Amplified PCR
      products were analyzed by the colorimetric microplate hybridization method in
      which a biotinylated PCR product was captured by streptavidin and hybridized with
      a digoxigenin-labelled oligonucleotide probe. In the final step an enzyme-linked
      antibody and a colorimetric reaction were utilized. A simple and rapid sample
      treatment was set up for the PCR detection of contaminants in beer. Detection of
      M. cerevisiae (> or = 5 x 10(3) colony forming units [cfu]/100 ml) and Pectinatus
      frisingensis (> or = 5 x 10(5) cfu/100 ml) in beer was successful, but the
      sensitivity of the assay still needs to be improved for direct detection of the
      small amounts of bacteria present in beer.

PMID- 9924943
TI  - Changes in the contents of fat-soluble vitamins and provitamins during tempe
      fermentation.
AB  - The content and formation of fat-soluble vitamins and provitamins during tempe
      fermentation was studied with 14 different strains of Rhizopus sp. All strains
      investigated form carotenoids in small amounts during fermentation, but beta
      carotene formation was only found in fermentations with six Rhizopus strains. The
      highest increase of beta-carotene production was to be seen from 34 to 48 h of
      fermentation. Soybean seeds did not contain ergosterol in detectable amounts.
      Ergosterol was produced by all Rhizopus strains in concentrations of up to 750
      microg g(-1) tempe dry weight (dw) during a 34 h fermentation period and of up to
      1610 microg g(-1) tempe dw during a 96 h fermentation period. The amounts of
      gamma-tocopherol in soybeans ranged from 192.4 to 231.8 microg g(-1) dw. Soybean
      seeds contained only free, not esterified tocopherols. During fermentation the
      total amount of vitamin E remained constant but the content of free tocopherols
      decreased. The content of vitamin K1 in soybeans is not strongly effected by
      tempe fermentation with pure cultures of Rhizopus sp.

PMID- 9924944
TI  - The spoilage flora of vacuum-packaged, sodium nitrite or potassium nitrate
      treated, cold-smoked rainbow trout stored at 4 degrees C or 8 degrees C.
AB  - The spoilage flora of vacuum-packaged, salted, cold-smoked rainbow trout fillets,
      with or without the addition of nitrate or nitrite, stored at 4 degrees C and 8
      degrees C, was studied. Of 620 isolates, lactic acid bacteria were the major
      fraction (76%), predominating in all samples of spoiled product. However, the
      phenotypical tests used were insufficient to identify the lactic acid bacteria to
      the species level. Gram-positive, catalase-positive cocci, gram-negative, oxidase
      negative rods and gram-negative, oxidase-positive rods were found in 6%, 16% and
      2% of the samples, respectively. Of 39 gram-positive, catalase-positive cocci, 29
      were identified as staphylococci and 10 as micrococci. Eighty-five isolates were
      found to belong to the family Enterobacteriaceae, with 45 of those being Serratia
      plymuthica. Eleven isolates from the nitrate treated samples stored at 8 degrees
      C were identified as Pseudomonas aeruginosa. The occurrence of P. aeruginosa and
      staphylococci in the nitrate-containing samples, stored at 8 degrees C, may cause
      problems with respect to the safety of the product. The types of lactic acid and
      other bacteria in the spoilage flora were generally reduced by the addition of
      nitrate or nitrite to fillets.

PMID- 9924945
TI  - Production of esters by Staphylococci.
AB  - The ability of resting cells and extracellular concentrates of Staphylococci to
      synthesize ethyl esters was studied in the presence of ethanol and short chain
      acids considered individually. All the strains synthesized ethyl esters, S.
      warneri was the highest producer and S. carnosus the lowest. Resting cells
      esterified preferentially butanoic acid, extracellular concentrates esterified
      butanoic, valeric and hexanoic acids. Acetic, decanoic and branched acids were
      poorly esterified. The activity of the extracellular concentrates with ethanol
      and butanoic acid was not modified by the pH (pH 5.5 or 7.0); but it was
      decreased at a temperature of 14 degrees C compared to 24 degrees C. For the
      resting cells it was the opposite, the activity was inhibited by acid pH and was
      not influenced by the temperatures. So the Staphylococci could produce esters
      during sausage manufacture.

PMID- 9924946
TI  - Interaction of Bifidobacterium and Salmonella during associated growth.
AB  - Interaction of 15 Bifidobacterium (belonging to species B. animalis, B. globosum
      and B. breve) and six Salmonella (belonging to species S. enteritidis and S.
      typhimurium) strains was examined during associated growth at optimum conditions
      for the two genera. All strains of Bifidobacterium investigated were antagonistic
      to Salmonella. Three strains of Bifidobacterium bactericidal to Salmonella were
      identified. The kinetics of Salmonella inhibition was as follows: growth of
      Salmonella was inhibited before the end of the exponential phase, then succeeded
      by a rapid decrease of live-cell numbers at the beginning of the stationary
      phase, after which the cell death rate was lower. Growth of Bifidobacterium in
      the associated cultures was similar to that in monocultures.

PMID- 9924947
TI  - Microbiological quality of Icelandic cooked-peeled shrimp (Pandalus borealis).
AB  - Iceland is a major producer of cold water shrimp, Pandalus borealis. In recent
      years considerable attention has been given to improve hygiene in the factories
      producing cooked, peeled and frozen shrimp. To keep track of the bacteriological
      status of the end product, shrimp from most of the factories is routinely
      analysed bacteriologically by the request of shrimp exporters. This paper reports
      on the results of a bacteriological analysis of 7913 samples of shrimp from 26
      Icelandic factories over a 6-year period. The results showed that the geometric
      mean of APC (at 35 degrees C) was 1718 per g and 57% of the samples had APC under
      1000 per g. Some 70% of the samples had less than one coliform per g and 99.9% of
      the samples had less than one faecal coliform per g. Staphylococcus aureus was
      detected in less than 0.2% of the samples. The results show improvement in
      bacterial profiles, mainly total coliforms, over the 6-year period. Overall, the
      results show acceptable bacterial numbers in the finished product, indicating a
      high level of hygiene. Listeria spp. were, however, found in 270 of 3331 samples
      examined or 8.1%. Species identification was done on 49 of the 270 positive
      samples. The proportion of L. monocytogenes was found to be 26.5%.

PMID- 9924948
TI  - Oat bran beta-gluco- and xylo-oligosaccharides as fermentative substrates for
      lactic acid bacteria.
AB  - The influence of oat bran oligosaccharides on carbohydrate utilization and
      fermentation end-products was studied with reference to three different lactic
      acid bacteria (LAB: Lactobacillus rhamnosus, Lactobacillus plantarum and
      Lactococcus lactis). The main results were that all three LAB utilized oat beta
      gluco-oligosaccharides, while only L. plantarum utilized xylo-oligosaccharides.
      The main products of LAB metabolism were lactic acid, acetic acid, formic acid
      and ethanol. The results indicated that oat beta-gluco-oligosaccharides and xylo
      oligosaccharides induce LAB to form the end-products of a typical mixed-acid
      fermentation. The formation of mixed-acid production from xylo-oligosaccharides
      was mainly due to the starvation of cells. This study indicates that oat bran
      oligosaccharides affect both qualitatively and quantitatively the fermentation
      end-products of LAB grown on these substrates. This should be taken into account
      when selecting strains for new fermented cereal based food products.

PMID- 9924949
TI  - Technology in neonatal intensive care--a study on parents' experiences.
AB  - A comprehensive health technology assessment is needed to meet the demands of
      holistic health care. We performed a qualitative study to describe the parents'
      experiences of the nursing care of sick newborn infants. The parents of seven
      full-term infants in a neonatal intensive care unit were interviewed. The parents
      found the intensive care unit shocking. The equipment with wiring, tubing and
      blinking lights looked frightening. The parents felt very unpleasant because of
      the audible signals. The technological environment was oppressive, which caused
      the parents to feel as outsiders in their parental role and delayed the
      development of their ability to participate in the care of the child. To relieve
      the anxiety of the parents and to promote their ability to take care of their
      newborn child, parental experiences should be taken into account when developing
      devices. Special attention should be given to designing the outside appearance
      and the audible signals and alarms of the equipment.

PMID- 9924950
TI  - Home polysomnography norms for children.
AB  - Home polysomnography (PSG) by means of ambulatory monitoring systems has distinct
      advantages over sleep laboratory recordings, especially for children. However,
      normative data have been lacking. Norms for conventional PSG variables were
      compiled for 60 children age 5-16 years using the Oxford Medilog ambulatory
      monitoring system. Recordings were confined to a single night in view of previous
      demonstrations that the sleep on the first night is not significantly affected by
      the recording procedure. The results are presented in 5 age subgroups. Broad
      comparisons with published laboratory PSG norms for children of the same ages
      suggest that in home recordings sleep duration is longer, and slow wave sleep is
      much more pronounced with a commensurate reduction in stage 2 NREM sleep. That
      is, sleep quality and quantity appears better at home even when adaptation to the
      laboratory situation has been promoted. These new normative data are considered
      valuable for both clinical and research purposes where physiological sleep
      studies in children are required.

PMID- 9924951
TI  - An opportunity for exploitation of research in biomedical engineering: the EC
      Life Sciences Demonstration Projects.
AB  - To validate clinically a new stereotactic device for real-time monitored
      minimally-invasive brain surgery; to perform the first European phase I clinical
      trials of Boron Neutron Capture Therapy (BNCT) for treatment of glioblastoma,
      using the facility of the Community Joint Research Centre (JRC) in Petten, on
      forty patients from six different European centres. These are typical objectives
      of the current EC BIOMED 2 demonstration projects. The number of supported
      projects under BIOMED is now 16 in 1998, and will be in total around 80 for the
      three Life Sciences and Technologies Programmes. Demonstration is expected to
      play a major role in the Fifth Framework Programme, particularly in its so-called
      "Key Actions". This article addresses three of the main issues for potential
      applicants: the readiness for demonstration, the content of the consortium, and
      the dissemination strategy.

PMID- 9924953
TI  - Principal stress analysis in LDA measurement of the flow field downstream of 19
      mm Sorin Bicarbon heart valve.
AB  - Heart valve replacement has become, since many years, a common surgical practice.
      Along with the improvement that the patients' health has derived from it,
      however, a certain amount of risk could not be avoided, bound to the inevitable
      hemodynamic disturbances that an artificial device generates. A major
      shortcoming, often reported, is the formation of thrombus on the edge of the
      prosthetic valve, with a possible obstruction of the orifices through which blood
      should normally flow undisturbed. Hemolysis is another possible consequence of
      the implantation of a mechanical heart valve, generally correlated to turbulence
      downstream of prosthetic heart valves (PHV). As it is agreed upon by many
      researchers, the risk of thrombogenicity or hemolysis is higher in those valves
      that are more subject to promote turbulence and flow separation in the flow
      through them. In the following paper, we present a study of the turbulence
      related shear stress downstream of a bileaflet valve of minimum size (19 mm
      external diameter) Sorin Bicarbon. This size was chosen, accordingly to the Food
      & Drug Administration (FDA) draft guidance suggestion to investigate the worst
      case in turbulence promoted by PHVs, in order to have the highest velocity
      gradients and shear stresses for the FDA-stated cardiac output (6 1/min), related
      to maximum Reynolds number conditions. Velocity data were collected with the two
      dimensional laser Doppler anemometry (LDA) technique; whereas this approach does
      not investigate directly all three components of the flow field, in the present
      case (bileaflet valves) it is not a limitation to the assessment of the maximum
      turbulence shear stress (TSS), thanks to the two-dimensional flow nature
      downstream of bileaflet models. Data taken in coincident mode were elaborated in
      order to determine the maximum shear stress in the measured points in the flow
      field, using the 2D Principal Stress Analysis (PSA). The consequences of a
      variable principal normal stress direction all along the measured profile will be
      illustrated in terms of differences between measured and maximum shear stresses.
      Results show the need to estimate the maximum values for the TSS and the
      direction along which it is obtained to correctly define the turbulent flow field
      downstream of PHVs.

PMID- 9924952
TI  - Evaluation of forced oscillation technique for early detection of airway
      obstruction in sleep apnea: a model study.
AB  - The forced oscillation technique (FOT) is a non-invasive method which may be
      suitable for assessing upper airway obstruction in obstructive sleep
      apnea/hypopnea syndrome (OSAS) patients. The aim of this study was to determine
      in vitro if FOT can provide an early detection index of total or partial upper
      airway occlusion. A respiratory system analog was developed which includes an
      upper airway analog that allows simulation of upper airway collapse (thus
      mimicking the situation in patients with OSAS). We simulated different degrees of
      upper airway obstructions ranging from 0 (unobstructed airways) to 1 (total
      occlusion). Furthermore, we imitated the collapsible upper airway wall by means
      of elastic membranes with ten different wall compliances ranging from 3.3 x 10(
      4) to 1 1/mbar. For the two stiffest rubber membranes (Cwall = 0.01 and 3.3 x 10(
      4) l/mbar) the absolute value of the impedance (?Z?) showed a marked increase for
      obstructions greater than 0.6. For the two membranes with the highest wall
      compliances (Cwall = 0.03 and 1 1/mbar) obstructions with an increase in ?Z?
      could not be detected before the obstruction reached 0.8. For degrees of
      obstruction less than 0.6 the phase angle of collapsible membranes with low
      compliance (stiff airway wall) were about 1.5pi which significantly differed from
      phase angles of 1.77pi measured in membranes with high compliance (elastic airway
      wall); p < 0.01. We hypothesized that stiffness of upper airway walls corresponds
      with their muscle tone, i.e., stiff airway walls are related with high muscle
      tone and vice versa. Thus, a decrease in upper airway muscle activity would cause
      an increase of upper airway wall elasticity that enables upper airway collapse.
      As a consequence the phase angle phi could be expected to change from values
      characterizing stiff membranes to values characterizing more elastic membranes
      which could be used as early indicator for obstructive respiratory events. We
      have frequently observed such changes in morphology of phi(t) data obtained from
      patients with OSAS.

PMID- 9924954
TI  - CE marking of medical devices.

PMID- 9924955
TI  - Estimation of analogue pre-filtering characteristics for CORSA standardisation.
AB  - This paper is concerned with devising a standard procedure for determining the
      gain and phase responses of the analogue filters used to pre-process pulmonary
      signals prior to their digitisation. The customary high-pass filtering, in
      particular, will strongly affect the time-domain wave-shapes of digitised signals
      and this must be taken into account when analysing the signals. Several means of
      determining the effect of the high-pass filtering are investigated and a
      measurement procedure is proposed which may be easily carried out using simple
      laboratory equipment.

PMID- 9924956
TI  - The epidemiology of malaria in Rondonia (Western Amazon region, Brazil): study of
      a riverine population.
AB  - We report on a longitudinal study concerning the incidence of malaria in a
      riverine population (Portuchuelo) settled on the riverbanks of Rio Madeira, in
      the State of Rondonia, Brazil. We found the incidence of malaria to be seasonal,
      prevailing in the dry months of June and July. The Annual Parasite Index (API)
      was 292/1000 inhabitants, almost three times that of the state of Rondonia for
      the same period. In contrast with other studied Rondonian populations, malaria in
      Portuchuelo was more prevalent in youngsters < 16 years old, particularly in the
      0-1 year age group. Adults were relatively spared, particularly those over 50
      years. Besides being indicative of indoor transmission, these facts may suggest
      the existence of a certain degree of acquired resistance to infection and/or of
      lessened symptoms in older people. Riverine populations are spread over the
      entire Amazon region where most of its members were born. Due to the permanent
      presence of malaria among riverine populations, we are proposing that they may
      act as perennial reserves of malaria and, therefore, as sources of infection for
      migrants or eventual settlers at their vicinity. To date, the opposite view has
      been generally held. Anopheles darlingi, the main vector species in the area, is
      essentially sylvatic, which contributes to make the control of malaria highly
      problematic. The only hopes for control rest on permanent surveillance and the
      prompt treatment of patients, which are also problematic considering the vastness
      of the Amazon region and the remoteness of some of its riverine settlements.

PMID- 9924957
TI  - Antibody response to the N and C-terminal regions of the Plasmodium vivax
      Merozoite Surface Protein 1 in individuals living in an area of exclusive
      transmission of P. vivax malaria in the north of Brazil.
AB  - Recently, we found that a recombinant protein based on the 19 kDa C-terminal
      region of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP1(19)) was
      recognized by a large proportion of individuals naturally infected. The present
      study was designed to determine the prevalence of antibody to PvMSP1(19) in
      individuals from the village of Cotijuba, northern Brazil, where only P. vivax
      transmission occurs. Immuno-epidemiological studies on the prevalence of antibody
      to the C-terminus of PvMSP1 are of particular importance as this region of MSP1
      is being intensively studied as a prime candidate for development of a vaccine
      against malaria. We evaluated the antibody response to PvMSP1(19), and compared
      it to the N-terminal region of PvMSP1 and to blood stage antigens. The total
      frequencies of individuals with IgG to blood stages, PvMSP1(19) or the N-terminal
      region of PvMSP1 were 76.6, 42.3 and 29.8%, respectively. The frequency of
      responders to PvMSP1(19) did not increase with age. However, the frequency of
      responders to this recombinant protein was significantly higher (77.4%) in
      individuals with a recent ( < 6 months) history of malaria, when compared to
      subjects whose last malaria attack occurred more than 6 months before (43.9%), or
      to individuals without a past history of symptomatic malaria (6.25%). These
      results confirm earlier studies by demonstrating that the PvMSP1(19) is highly
      immunogenic in individuals recently exposed to P. vivax malaria.

PMID- 9924958
TI  - Human intestinal infection due to coccidia in Mozambique: two cases.
AB  - A case of intestinal infection by Cryptosporidium parvum and another of
      intestinal Isospora belli infection, both in AIDS patients, are described. The
      two patients presented pulmonary tuberculosis symptoms and watery diarrhoea.
      Modified Ziehl-Neelsen stain of stools gave a definitive diagnosis in both cases.
      They are the first reports of intestinal coccidia infections in AIDS patients
      described in Mozambique.

PMID- 9924959
TI  - Saliva ELISA: a method for the diagnosis of chronic Chagas disease in endemic
      areas.
AB  - An indirect enzyme linked immunosorbent assay (ELISA) was applied to saliva to
      detect chronic infection by Trypanosoma cruzi in humans. Saliva samples from 114
      Chagas' disease chronically infected individuals, characterized by three
      serological tests and clinical evaluation and from 100 healthy controls were
      tested for T. cruzi specific IgG antibodies. At dilution of 1 in 2, specific
      antibodies were detected in saliva samples from 103 of 114 samples from infected
      patients and 5 of 100 controls (sensitivity 90.4%, specificity 95%). There was no
      significant correlation between the antibody titre and cardiac or
      gastrointestinal tract disease. This assay possesses some advantages over other
      methods as saliva collection is non-invasive, requires no special equipment and
      whole saliva gave reproducible results. Although serology remains the gold
      standard for T. cruzi infection, these results suggest that T. cruzi specific
      salivary antibody detection may provide a screening diagnostic test and
      contribute to epidemiological studies of chronic trypanosomiasis infection in
      endemic areas.

PMID- 9924960
TI  - Plant products used as mosquito repellents in Guinea Bissau, West Africa.
AB  - By standardized interviews of people in 23 rural villages, in the Oio region of
      Guinea Bissau, we collected data on which plant species and plant derived
      products or methods people use to reduce mosquito biting activity. The following
      plants were used to reduce numbers of mosquitoes indoors at night: fresh or
      smouldering Hyptis suaveolens Poit. (Lamiaceae), smoke of the bark of Daniellia
      oliveri Rolfe (Caesalpiniaceae), smoke of the infructescence of Elaeis guineensis
      Jacq. (Arecaceae), smoke of the seed capsules of Parkia biglobosa (Jacq.) Benth.
      (Mimosaceae), smoke of the leaves of Azadirachta indica A.Juss. (Meliaceae) and
      Eucalyptus sp. (Myrtaceae), fresh Ocimum canum Sims (Lamiaceae), and fresh Senna
      occidentalis (L.) Link (Caesalpiniaceae). In two field experiments we estimated
      the 'repellent activity' of certain of these plants and compared their efficacies
      with those of two commercially available mosquito repellents, i.e. 'positive'
      controls. In the first experiment we tested: smouldering H. suaveolens (85.4%
      repellency); fresh H. suaveolens (73.2%); burning of the bark of D. oliveri
      (74.7%); and smoke of the leaves of Eucalyptus (72.2%). In the second experiment
      we tested: smouldering H. suaveolens (83.6% repellency); fresh H. suaveolens
      (66.5%); burning of the bark of D. oliveri (77.9%); smoke of the leaves of A.
      indica (76.0%); smoke of the infructescence of E. guineensis (69.0%); fresh O.
      canum (63.6%); and fresh S. occidentalis; (29.4%). All the products tested,
      except S. occidentalis were significantly more effective than the negative
      control.

PMID- 9924961
TI  - Praziquantel side effects and efficacy related to Schistosoma mansoni egg loads
      and morbidity in primary school children in north-east Ethiopia.
AB  - A total of 611 Schistosoma mansoni infected primary school children from three
      schools in north-east Ethiopia were treated with praziquantel at 40 mg/kg body
      weight in a single dose. Pre-treatment, 40.4% had no presenting symptoms and 30
      40% had nausea, abdominal cramps and/or bloody-mucoid diarrhoea. None of the pre
      treatment symptoms was related to nutritional status, intensity of S. mansoni egg
      excretion, or to the presence of other concomitant intestinal parasitic
      infections. During the first 4-6 h post-treatment observation period, 90 (14.7%)
      children self-presented with severe gastro-intestinal symptoms. Children who self
      presented with severe symptoms had a higher mean age and mean S. mansoni egg
      excretion compared with children who did not self-present. The following day a
      total of 529 (86.6%) children, including all who self-presented during the first
      4-6 h post-treatment, reported for clinical check-up and were subjected to a
      structured questionnaire interview on symptoms they had experienced over the time
      lapse following treatment. Among these, 91.5% reported one or more treatment
      related symptoms which were at times severe. Abdominal cramps (86.9%), diarrhoea
      with blood and/or mucus (49.5%), dizziness (31.2%) and vomiting (24.9%) were the
      most common treatment related symptoms. Skin rash with oedema were observed in
      four cases. Among treatment related symptoms, the combination of abdominal cramps
      with vomiting, bloody diarrhoea, vomiting alone and general weakness were
      significantly higher among the malnourished. A proportion of these symptoms
      increased with increasing categories of S. mansoni egg excretion before and after
      adjusting for nutritional status and concurrent intestinal parasitic infections.
      Overall, the cure rate of praziquantel, among 541 children who had stool
      examination 5 weeks after treatment was 83.2% and this rate decreased with
      increasing pre-treatment egg counts. In conclusion, most of the treatment related
      symptoms were mild. However, some of the objective symptoms were at times severe
      and may reduce drug compliance in primary health care based population
      chemotherapy.

PMID- 9924962
TI  - Polymerase chain reaction characterization of trypanosomes in Glossina morsitans
      submorsitans and G. tachinoides collected on the game ranch of Nazinga, Burkina
      Faso.
AB  - The polymerase chain reaction was used to characterize the trypanosomes infecting
      Glossina morsitans submorsitans and G. tachinoides in the game ranch of Nazinga,
      Burkina Faso, situated near an agropastoral zone. Dissection of 435 tsetse flies,
      and PCR analysis of 166 infected flies were conducted to assess the
      epidemiological situation. Trypanosomes of the Nannomonas subgenus were the most
      abundant in the two tsetse species (80.4% and 73.7% of identified infections in
      G. m. submorsitans and G. tachinoides respectively). T. vivax and T. brucei
      infection rates were comparable between the two tsetse species. Mature infection
      pattern identified by PCR differed from overall infections, mainly because T.
      simiae infections did not mature, whereas T. vivax represented the predominant
      taxon. Parasitological and PCR results showed some discrepancies; possibly some
      typical Duttonella strains could not be recognized by the sets of primers used.
      The technologies used in this work helped to determine the high trypanosomosis
      risk in this area.

PMID- 9924964
TI  - Differences in saliva composition among three Brazilian populations of
      Panstrongylus megistus (Hemiptera, Reduviidae).
AB  - Comparisons of electrophoretic profiles of triatomines (Panstrongylus megistus)
      from the Brazilian states of Bahia (BA), Minas Gerais (MG) and Santa Catarina
      (SC) revealed differences in the composition of the saliva between the three
      populations. A phenogram constructed on the basis of the most representative
      electrophoretic banding patterns allowed the specimens tested to be divided into
      two groups. The BA and SC populations could be completely separated while some
      individuals from MG could be placed in each group. The BA population presented
      fewer bands than the MG and SC ones. The populations studied also differed with
      regard to their degree of association with human habitations (sylvatic,
      peridomiciliary and/or intradomiciliary) and our results suggest that the
      proteinaceous composition of the saliva of the three distinct populations of
      triatomines could be related to the hosts each is likely to encounter.

PMID- 9924963
TI  - Identification of African Paragonimidae by multivariate analysis of the eggs.
AB  - A study of metacercariae and adult Paragonimidae revealed the existence in West
      Africa of four species, of which two are largely recorded in literature
      (Paragonimus africanus and Paragonimus uterobilateralis), one was suspected
      (Paragonimnus westermani-like) and one remained unrecorded in Africa
      (Euparagonimus sp). Among the two last ones, P. westermani-like was probably
      confused with P. africanus, and Euparagonimus sp. with P. uterobilateralis. P.
      westermani-like adult worms differed from P. africanus by the morphology of
      ovary, testes and the size of the metraterm eggs. Euparagonimus could be
      identified by a short excretory bladder in metacercariae. The discriminant
      functions established on eggs measurements (average, maximum and minimum length,
      average, maximum and minimum width) were able to separate the isolates into four
      groups. The largest eggs (97 x 59 microm) belonged to P. westermani-like, the
      medium sized eggs were ascribed to P. africanus (91 x 49 microm) and to
      Euparagonimus sp. (84 x 50 microm), and the smaller eggs (69 x 42 microm) were
      identified as P. uterobilateralis. Three Paragonimidae were identified in
      Cameroon: P. westermani-like, P. africanus and Euparagonimus sp. Additionally, P.
      uterobilateralis, P. westermani-like, and Euparagonimus sp. were found in the
      Congo, Gabon, and the Ivory Coast, respectively.

PMID- 9924965
TI  - In vitro promastigote fitness of putative Leishmania (Viannia)
      braziliensis/Leishmania (Viannia) peruviana hybrids.
AB  - In order to initiate studies on the phenotypic properties of hybrids vs. their
      putative parents, the in vitro growth behaviour of promastigotes was compared for
      15 stocks characterised as Leishmania (Viannia) braziliensis, Leishmania
      (Viannia) peruviana and putative hybrids (isolated from the Eastern Andean valley
      of Huanuco, Peru). Five sets of three stocks, each set including a
      L.(V.)braziliensis, a L.(V.)peruviana and a putative hybrid, were constituted
      randomly and counted daily close to isolation from man (ten to 18 subcultures).
      Hybrids and L.(V.)peruviana presented similar growth characteristics, and they
      displayed a growth capacity (growth rate and cell density at stationary phase)
      significantly lower than the one of L.(V.)braziliensis. Following prolonged in
      vitro maintenance of one of the sets, the hybrid kept its lower growth capacity.
      The contrast between the difficulty to grow in vitro these putative hybrids, and
      their high isolation rate from natural populations is discussed.

PMID- 9924966
TI  - A drug incubation Glossina infectivity test (DIGIT) to assess the susceptibility
      of Trypanosoma congolense bloodstream forms to trypanocidal drugs
      (Xenodiagnosis).
AB  - Blood was collected from two Sahelian goats, experimentally infected with either
      a drug-sensitive cloned population of Trypanosoma congolense (IL 1180) or a
      multiple drug-resistant T. congolense stock (Samorogouan/89/CRTA/267) and
      incubated at 37 degrees C for 30 min and 12 h, respectively, in the presence of
      different drug concentrations (0.5, 1.0, 10.0 and 100.0 microg/ml blood) of
      diminazene aceturate or isometamidium chloride. After that, the
      trypanosome/blood/drug suspensions were offered to tsetse flies (2100 teneral
      Glossina morsitans submorsitans) through an in vitro feeding system, using a
      silicone membrane. All tsetse flies were dissected and examined for the presence
      of trypanosomes in labrum, hypopharynx and midgut 20 days after their infective
      blood-meals. Infectivity of the drug-sensitive cloned population was already
      completely abolished after incubation with 0.5 microg/ml of both drugs; however,
      13.6-42.2% of tsetse having been fed on untreated blood had developed an
      infection. In contrast, no significant differences were observed in the infection
      rates between the experimental groups and their control groups when fed on blood
      infected with the multiple drug-resistant stock after incubation for 30 min with
      up to 10 microg/ml of diminazene or isometamidium. In consequence, tsetse appear
      to be a useful tool in the assessment of drug susceptibility of typanosome
      populations.

PMID- 9924967
TI  - Yeast culture volatiles as attractants for Rhodnius prolixus: electroantennogram
      responses and captures in yeast-baited traps.
AB  - Responses to air currents carrying volatiles from yeast cultures were measured by
      means of electroantennograms (EAGs) in the haematophagous bug Rhodnius prolixus
      and we tested yeast-baited traps in the laboratory. The volatiles liberated by
      yeast cultures generated a clear electrophysiological response, much higher than
      that obtained during stimulation with clean air. The addition of yeast cultures
      to the traps dramatically increased overnight capture. A modification performed
      on the traps was effective for this species, as the bugs were immobilised once
      they fell into the device. Our results demonstrate that yeast culture volatiles
      are attractive for R. prolixus. The results obtained by means of
      electroantennogram techniques represent the first electrophysiological evidence
      of the perception of yeast volatiles by the antennae of a triatomine bug. We
      discuss the relevance of our results in view of currently used sampling
      techniques and control strategies.

PMID- 9924968
TI  - Prevalence of intestinal parasites in Cuban acquired immunodeficiency syndrome
      (AIDS) patients.
AB  - A coproparasitological study was carried out on 67 acquired immunodeficiency
      syndrome (AIDS) patients admitted at the Institute of Tropical Medicine 'Pedro
      Kouri'. The results were compared with 136 HIV-seronegative patients (control
      group) who were also hospitalised in the same period. In both groups
      monoparasitism was more prevalent than polyparasitism and intestinal protozoa
      were more prevalent than helminths. At least one intestinal parasite was found in
      34 (51%) of the 67 AIDS patients and in 65 (48%) of the control group patients.
      Intestinal coccidia were only detected in AIDS patients; Cryptosporidium spp. was
      the most prevalent, with eight cases (11.9%), followed by Cyclospora cayetanensis
      with two cases (3.0%) and Isospora belli in one case (1.5%). The microsporidia
      Encephalitozoon (Septata) intestinalis and Enterocytozoon bieneusi were not
      detected. With regard to the prevalence of other pathogenic intestinal parasites
      in AIDS patients and the control group, no differences were found.

PMID- 9924969
TI  - MAP2 expression in developing dendrites of human brainstem auditory neurons.
AB  - Immunostaining of cytoskeletal elements has proved to be a useful technique for
      tracing ontogenetic development in the human central auditory system. In the
      present study, dendritic development in brainstem auditory nuclei (dorsal and
      ventral cochlear nuclei, medial and lateral superior olivary nuclei, and inferior
      colliculus) was studied using an antibody to a microtubule-associated protein,
      MAP2, a molecule which stabilizes dendritic processes by promoting assembly of
      microtubules. At 21-22 weeks of gestation, cells within the auditory nuclei first
      demonstrate cytoplasmic MAP2 immunoreactivity, but no dendritic structures have
      formed. Filamentous background staining at this stage may represent
      immunoreactivity in astrocytic processes. By the 24th fetal week, somata of
      auditory neurons are strongly immunostained and have developed short dendritic
      processes. During the perinatal period, dendrites extend up to 100-120 microm in
      length but are still sparsely branched and lack terminal formations. By the sixth
      postnatal month, neurons in all auditory nuclei have acquired dendritic arbors
      with a mature appearance. Thus MAP2 immunohistochemistry demonstrates that
      dendrogenesis in human brainstem auditory nuclei begins 16 weeks prior to term
      birth but does not reach the stage of mature dendritic morphology until several
      months into the postnatal period. This extended course of development implies a
      significant period of time during which neuronal activity could influence
      dendritic structure and function.

PMID- 9924970
TI  - Immunohistochemical localization of DARPP32 in striatal projection neurons and
      striatal interneurons in pigeons.
AB  - DARPP32 is a D1-receptor associated signaling protein found in striatal
      projection neurons in mammals, including both substance P-containing (SP+)
      neurons and enkephalinergic (ENK+) projection neurons. The present study used
      immunohistochemical single- and double-labeling to examine the cellular
      localization of DARPP32 in pigeon striatum. Single-label studies revealed that
      DARPP32 is present in numerous medium-sized striatal perikarya and DARPP32+ axons
      and terminals were seen to profusely innervate the two major striatal projection
      targets, the pallidum and the substantia nigra. The single-labeling studies
      indicated that about 60% of all striatal perikarya labeled for DARPP32+ in
      striatum, which exceeds the abundance of either SP+ or ENK+ perikarya. Single
      labeling studies also showed that the abundance of DARPP32+ fibers and terminals
      in pallidum exceeds that of either SP+ or ENK+ fibers and terminals in pallidum.
      Double-labeling found that 30-50% of striatal SP+ perikarya and 7-24% of ENK+
      striatal perikarya labeled for DARPP32 in pigeon, and confirmed that DARPP32 was
      found in both SP+ and ENK+ fibers and terminals in pallidum. In contrast to its
      prevalence in striatal projection neurons, DARPP32 was virtually absent from
      cholinergic and NPY+ striatal interneurons, as also true in mammals. Our data are
      consistent with the interpretation that many SP+ neurons and many ENK+ neurons in
      avian striatum possess D1-type dopamine receptors and use a DARPP32 signalling
      pathway, although this may be more common for SP+ than for ENK+ neurons.

PMID- 9924971
TI  - What are the facts and artifacts of the pathogenesis and etiology of Alzheimer
      disease?
AB  - Over the past decade, an increased clinical awareness, together with advances in
      biochemical, cellular, and molecular analyses, have catapulted the study of
      Alzheimer disease to the forefront of biomedical research. During this time, a
      great number of theories, regarding disease pathogenesis, have come and gone but
      several have persisted. Here, we critically evaluate these theories in an attempt
      to delineate the facts from the artifacts.

PMID- 9924972
TI  - Aromatic L-amino acid decarboxylase- and tyrosine hydroxylase
      immunohistochemistry in the adult human hypothalamus.
AB  - The distribution of cell bodies immunoreactive for tyrosine hydroxylase and
      aromatic L-amino acid decarboxylase was studied in the adult human hypothalamus.
      Many neurons in the posterior (A11) and caudal dorsal hypothalamic areas (A13) as
      well as in the arcuate (A12) and periventricular (A14) zone were immunoreactive
      for the two enzymes, suggesting that they were dopaminergic. Numerous tyrosine
      hydroxylase-immunoreactive neurons, which were not immunoreactive for aromatic L
      amino acid decarboxylase, could be seen in the paraventricular, supraoptic and
      accessory nuclei (A15) as well as in the rostral dorsal hypothalamic area. These
      were considered to be non-dopaminergic. Conversely, large numbers of small
      neurons immunoreactive for aromatic L-amino acid decarboxylase but not for
      tyrosine hydroxylase, were identified in the premammillary nucleus (D8), zona
      incerta (D10), lateral hypothalamic area (D11), anterior portion of the
      dorsomedial nucleus (D12), suprachiasmatic nucleus (D13), medial preoptic area
      and bed nucleus of the stria terminalis (D14). In the human hypothalamus, besides
      dopaminergic cell bodies, there exists a large number of tyrosine hydroxylase
      only and aromatic L-amino acid decarboxylase-only neurons, whose physiological
      roles remain to be determined.

PMID- 9924973
TI  - Changes in GAD- and GABA- immunoreactivity in the spinal dorsal horn after
      peripheral nerve injury and promotion of recovery by lumbar transplant of
      immortalized serotonergic precursors.
AB  - We have utilized RN46A cells, an immortalized neuronal cell line derived from E13
      brainstem raphe, as a model for transplant of bioengineered serotonergic cells.
      RN46A cells require brain-derived neurotrophic factor (BDNF) for increased
      survival and serotonin (5HT) synthesis in vitro and in vivo. RN46A cells were
      transfected with the rat BDNF gene, and the 46A-B14 cell line was subcloned.
      These cells survive longer than 7 weeks after transplantation into the
      subarachnoid space of the lumbar spinal cord and synthesize 5HT and BDNF. Chronic
      constriction injury (CCI) of the sciatic nerve was used to induce chronic
      neuropathic pain in the affected hindpaw in rats. Transplants of 46A-B14 cells
      placed 1 week after CCI alleviated chronic neuropathic pain, while transplants of
      46A-V1 control cells, negative for 5HT and without the BDNF gene, had no effect
      on the induction of thermal and tactile nociception. When endogenous cells of the
      dorsal horn which contain the neurotransmitter gamma-aminobutyric acid (GABA) and
      its synthetic enzyme glutamate decarboxylase (GAD) were immunohistochemically
      quantified in the lumbar spinal cord 3 days and 1-8 weeks after CCI, the number
      of GABA- and GAD-immunoreactive (ir) cells decreased bilateral to the nerve
      injury as soon as 3 days after CCI. At 1 week after CCI, the number of GABA-ir
      cells continued to significantly decline bilaterally, returning to near normal
      numbers on the side contralateral to the nerve injury by 8 weeks after the nerve
      injury. The number of GAD-ir cells began to increase bilaterally to the nerve
      injury at 1 week after CCI and continued to significantly increase in numbers
      over normal values by 8 weeks after the nerve injury. When examined 2 and 8 weeks
      after CCI plus cell transplants, the transplants of 46A-B14 cells reversed the
      increase in GAD-ir cell numbers and the decrease in GABA-ir cells by 1 week after
      transplantation, while 46A-V1 control cell transplants after CCI had no effect on
      the changes in numbers of GAD-ir or GABA-ir cells. Collectively, these data
      suggest that altered 5HT levels, and perhaps BDNF secretion, related to the
      transplants ameliorate chronic pain and reverse the induction and maintenance of
      an endogenous pain mechanism in the dorsal horn. This induction mechanism is
      likely dependent on altered GAD regulation and GABA synthesis, initiated by CCI.

PMID- 9924974
TI  - Supramolecular ligands: monomer structure and protein ligation capability.
AB  - The aim of this work was to define the chemical structure of compounds self
      assembling in water solutions, which appear to interact with proteins as single
      ligands with their supramolecular nature preserved. For this purpose the ligation
      to proteins of bis azo dyes, represented by Congo red and its derivatives with
      designed structural alterations, were tested. The three parameters which
      characterize the reactivity of supramolecular material were determined in the
      same conditions for all studied dyes. These were: A) stability of the assembly
      products; B) binding to heat-denatured protein (human IgG); and C) binding to
      native protein (rabbit antibodies in the immune complex) measured by the
      enhancement of hemagglutination. The structural differences between the Congo red
      derivatives concerned the symmetry of the molecule and the structure of its non
      polar component, which occupies the central part of the dye molecule and is
      thought to be crucial for self-assembly. Other dyes were also studied for the
      same purpose: Evans blue and Trypan blue, bis-ANS and ANS, as well as a group of
      compounds with a structural design unlike that of bis azo dyes. Compounds with
      rigid elongated symmetric molecules with a large non-polar middle fragment are
      expected to form a ribbon-like supramolecular organization in assembling. They
      appeared to have ligation properties related to their self-assembling tendency.
      The compounds with different structures, not corresponding to bis azo dyes, did
      not reveal ligation capability, at least in respect to native protein. The
      conditions of binding to denatured proteins seem less restrictive than the
      conditions of binding to native molecules. The molten hydrophobic protein
      interior becomes a new binding area allowing for complexation of even non
      assembled molecules.

PMID- 9924975
TI  - Effect of polyisobutylcyanoacrylate nanoparticles and lipofectin loaded with
      oligonucleotides on cell viability and PKC alpha neosynthesis in HepG2 cells.
AB  - The aim of the present study was to evaluate the inhibitory effect on protein
      kinase C alpha (PKC alpha) neosynthesis of antisense oligonucleotides delivered
      by two types of carriers. First, PKC alpha antisense oligonucleotides were
      associated with polyisobutylcyanoacrylate (PIBCA) nanoparticles pre-coated with
      cetyltrimethyl ammonium bromide (CTAB), a hydrophobic cation. Adsorption of
      oligonucleotides onto PIBCA nanoparticles was shown to be a saturating process.
      From these studies, it was possible to identify two types of particles:
      positively and negatively charged. Secondly, Lipofectin was used as another
      carrier system. These systems were incubated with HepG2 cells. Toxicity was
      evaluated by the MTT assay, and PKC alpha neosynthesis was determined by Western
      blots in conditions where nanoparticles and Lipofectin were not inducing
      cytotoxicity. It was observed that both mismatch and antisense oligonucleotides
      induced an inhibition of PKC alpha neosynthesis when loaded onto cationic or
      anionic nanoparticles as well as when complexed to cationic liposomes
      (Lipofectin). This non-specific effect was only observed in the phase of PKC
      alpha neosynthesis when the cells were first depleted in PKC alpha by phorbol 12
      myristate beta-acetate (12-PMA) and in the absence of serum. These results
      strongly suggest that delivery systems, PIBCA nanoparticles or Lipofectin,
      containing a positively charged component (CTAB or cationic lipids), are able to
      induce a perturbation in the intracellular metabolic activity. In conclusion, it
      was shown that the commonly used strategy of oligonucleotides targeting with
      cationic non-viral vectors may display non-specific effects which can lead to
      artifactual results.

PMID- 9924976
TI  - A pseudoknotted tRNA variant is a substrate for tRNA (cytosine-5)
      methyltransferase from Xenopus laevis.
AB  - tRNA post-transcriptional modification enzymes of Xenopus laevis were proposed
      previously to belong to two major groups according to their sensitivity to
      structural perturbations in their substrates. To further investigate the
      structural variations tolerated by these enzymes, the tRNA-like domain of turnip
      yellow mosaic virus RNA (88 nucleotides in length) has been microinjected into
      the oocytes of Xenopus laevis. This RNA possesses 12 potential target nucleotides
      for modification within a structure including a pseudoknotted folding, an
      extended anticodon stem, and unusual D-loop/T-loop interactions. Results indicate
      that only cytosine-42, a position equivalent to C-49 in canonical tRNAs, was
      quantitatively modified into m5C in the microinjected RNA. Modification was
      detected to high levels, indicating that at least one enzyme tolerates non
      canonical structural features.

PMID- 9924977
TI  - Selected phenotypes of ihf mutants of Escherichia coli.
AB  - In attempts to identify subunit-specific phenotypes of ihf mutants we analyzed
      viability, thermoresistance and protein synthesis patterns in ihfA and ihfB
      mutants and their respective parental strains. Despite some detected differences
      in the two-dimensional protein patterns, no significant subunit-specific,
      physiological effects could be observed. Each mutant was less viable and less
      thermoresistant than the wild type strain. Moreover, in contrast to the wild type
      the mutants did not reduce global protein synthesis after prolonged culturing.
      Examination of expression of transcriptional fusions allowed us to demonstrate
      autoregulation of both genes by IHF. Additional IHF binding sites in the
      regulatory region of both ihf genes were footprinted.

PMID- 9924978
TI  - The protein sequence of an archaeal catalase-peroxidase.
AB  - The gene encoding a catalase-peroxidase of archaeal origin, the halophilic
      catalase-peroxidase from Haloarcula marismortui, was sequenced. The primary
      structure proposed was confirmed by Edman degradation and mass spectrometry
      analyses of proteolytic fragments of the purified protein. The open reading frame
      in the gene corresponds to 731 amino acids and the calculated mass of the mature
      protein (deleted of the N-terminal methionine) is 81,253.65 Da, in reasonable
      agreement with the value of 81,292 +/- 9 Da previously measured by mass
      spectrometry. Southern and Northern blot analyses showed that the protein is
      encoded by a single gene as a monocistronic transcript. The protein sequence
      shows a high level of identity with bacterial catalase-peroxidases, with strongly
      conserved regions around the heme binding histidines. Similarly to other soluble
      halophilic proteins, it shows the excess of acidic residues that has been
      associated with solvation in halophilic adaptation.

PMID- 9924979
TI  - 13C-NMR spectroscopic evaluation of the citric acid cycle flux in conditions of
      high aspartate transaminase activity in glucose-perfused rat hearts.
AB  - A new mathematical model, based on the observation of 13C-NMR spectra of two
      principal metabolites (glutamate and aspartate), was constructed to determine the
      citric acid cycle flux in the case of high aspartate transaminase activity
      leading to the formation of large amounts of labeled aspartate and glutamate. In
      this model, the labeling of glutamate and aspartate carbons by chemical and
      isotopic exchange with the citric acid cycle are considered to be interdependent.
      With [U-13C]Glc or [1,2-(13)C]acetate as a substrate, all glutamate and aspartate
      carbons can be labeled. The isotopic transformations of 32 glutamate isotopomers
      into 16 aspartate isotopomers or vice versa were studied using matrix operations;
      the results were compiled in two matrices. We showed how the flux constants of
      the citric acid cycle and the 13C-enrichment of acetyl-CoA can be deduced from
      13C-NMR spectra of glutamate and/or aspartate. The citric acid cycle flux in
      beating Wistar rat hearts, aerobically perfused with [U-13C]glucose in the
      absence of insulin, was investigated by 13C-NMR spectroscopy. Surprisingly,
      aspartate instead of glutamate was found to be the most abundantly-labeled
      metabolite, indicating that aspartate transaminase (which catalyses the
      reversible reaction: (glutamate + oxaloacetate <--> 2-oxoglutarate + aspartate)
      is highly active in the absence of insulin. The amount of aspartate was about two
      times larger than glutamate. The quantities of glutamate (G0) or aspartate (A0)
      were approximately the same for all hearts and remained constant during
      perfusion: G0 = (0.74 +/- 0.03) micromol/g; A0 = (1.49 +/- 0.05) micromol/g. The
      flux constants, i.e., the fraction of glutamate and aspartate in exchange with
      the citric acid cycle, were about 1.45 min(-1) and 0.72 min(-1), respectively;
      the flux of this cycle is about (1.07 +/- 0.02) micromol min(-1) g(-1). Excellent
      agreement between the computed and experimental data was obtained, showing that:
      i) in the absence of insulin, only 41% of acetyl-CoA is formed from glucose while
      the rest is derived from endogenous substrates; and ii) the exchange between
      aspartate and oxaloacetate or between glutamate and 2-oxoglutarate is fast in
      comparison with the biological transformation of intermediate compounds by the
      citric acid cycle.

PMID- 9924980
TI  - Reactivity of trypsin in reverse micelles: pH-effects on the W0 versus enzyme
      activity profiles.
AB  - pH-Dependence of hydrolytic activity of trypsin has been studied in cationic
      reverse micellar system of cetyltrimethylammonium bromide (CTAB) in (50% v/v)
      chloroform/isooctane using a positively charged substrate N(alpha)-benzoyl-L
      arginine ethyl ester (BAEE). The pH of the medium was varied from 4.0 to 8.5 with
      addition of 0.025 M citrate-phosphate buffer containing 1 mM CaCl2. Optimum pH
      for maximum enzyme activity, pH(opt) in reverse micelles is found to be similar
      to that observed in bulk aqueous solution (8.0-8.5). However, changes in activity
      of trypsin (k(cat)) as a function of water content W0 (W0 = [H2O]/[CTAB]) in
      reverse micelles are found to be pH dependent. At low pH (4.0) and low water
      content (W0 = 5) the enzyme is more active in reverse micelles than in bulk
      aqueous solution by a factor of 2. This 'superactivity' is lost at higher W0
      values and the k(cat) in reverse micelles is found to be similar to that observed
      in aqueous bulk. At pH 5, the enzyme activity is found to be independent of W0
      while at pH 6.0-6.5 the enzyme activity is low at W0 5 and increases with water
      content to a constant value which is still 50% lower than that in aqueous buffer.
      Above pH 7, the W0-activity profile becomes distinctly bell shaped with W0
      optimum around 10-15. The enzyme activity at optimum W0 is close to that observed
      in aqueous bulk.

PMID- 9924981
TI  - Linker histone binding to superhelical DNA: electrophoretic and filter binding
      studies.
AB  - It has been known for years that linker histones bind preferentially to
      supercoiled DNA. This preference has been demonstrated by a number of different
      techniques including deoxyribonucleoprotein electrophoresis, sedimentation, and
      filter binding under non-competitive conditions. In an attempt to further study
      this issue, we used one- and two-dimensional electrophoretic gels and filter
      binding under competitive conditions, with all DNA forms of interest being
      simultaneously present in the incubation mixture. Comparison between results
      obtained by the two methods showed that whereas the preference for superhelical
      molecules was clearly seen in the electrophoretic gels, the filter binding assay
      failed to reveal this preference. These results reveal limitations to the filter
      binding technique, which must be borne in mind in studies involving superhelical
      DNA molecules.

PMID- 9924982
TI  - Viruses: exquisite models for cell strategies.
AB  - Because of the small size of their genome, viral genes have been forerunners in
      helping us understand gene expression. It is also because of their small size
      that viruses have elaborated the amazing variety of strategies that enables them
      to produce all the proteins they require for their multiplication. As a
      consequence, many of the strategies of expression known to occur in cell systems
      were first demonstrated in viruses. The aim of this review is to highlight the
      contribution of viruses to our knowledge of cell processes.

PMID- 9924983
TI  - Increased expression of a hemimethylated oriC binding protein, SeqA, in an aphA
      mutant.
AB  - In Escherichia coli, the origin of DNA replication, oriC, becomes transiently
      hemimethylated at the GATC sequences immediately after initiation of replication
      and this hemimethylated state is prolonged because of its sequestration by a
      fraction of outer membrane. This sequestration is dependent on a hemimethylated
      oriC binding protein such as SeqA. We previously isolated a clone of phage lambda
      gt11 called hobH, producing a LacZ fusion protein which recognizes hemimethylated
      oriC DNA. Very recently, Thaller et al. (FEMS Microbiol. Lett. 146 (1997) 191
      198) found that the same DNA segment encodes a non-specific acid phosphatase, and
      named the gene aphA. We show here that the interruption of the aphA reading frame
      by kanamycin resistance gene insertion, abolishes acid phosphatase (NAP)
      activity. Interestingly, in the membrane of the null mutant, the amount of SeqA
      protein is about six times higher than that in the parental strain, suggesting
      the existence of a regulatory mechanism between SeqA and NAP expression.

PMID- 9924984
TI  - Inhibitory effects of anions and active site amino acid sequence of chicken liver
      L-2-hydroxyacid oxidase A, a member of the FMN-dependent alpha-hydroxyacid
      oxidizing enzyme family.
AB  - Monocarboxylic acids with aliphatic chains were found to be mixed inhibitors of
      chicken liver L-2-hydroxyacid oxidase A when L-2-hydroxy-4-methylthiobutanoic
      acid was used as the substrate. The finding that the binding affinity of the
      enzyme for monocarboxylic acids was directly proportional to the number of carbon
      atoms in the chain strongly suggests that in addition to the electrostatic
      interaction due to the carboxyl moiety, hydrophobic forces may also be involved
      in the binding affinity of monocarboxylic acids to the enzyme's active site.
      Oxalate, a dicarboxylic acid, also resulted in a mixed-type inhibition of chicken
      liver L-2-hydroxyacid oxidase A, and, surprisingly, its binding affinity to the
      enzyme was found to be quite high as compared with monocarboxylic acids. This is
      probably due to the fact that the two carboxyl groups of oxalate give rise to
      electrostatic interactions with the positively charged side chains of two
      adjacent residues in the polypeptide chain. The inhibitory effects of other
      dicarboxylic acids was found to decrease as the number of carbon atoms in the
      chain increased. Oxamate was found however to be a novel type of potent inhibitor
      of the enzyme. All in all, these kinetic studies and the amino acid sequence
      determination in the active site region after limited proteolysis of the
      polypeptide chain definitely establish that chicken liver NADH/FMN containing L-2
      hydroxyacid oxidase A is a member of the FMN-dependent alpha-hydroxyacid
      oxidizing enzyme family.

PMID- 9924985
TI  - Phospholipid dependence of membrane-bound phospholipase A2 in ras-transformed NIH
      3T3 fibroblasts.
AB  - Although the activation of phospholipase A2 (PLA2) in ras-transformed cells has
      been well documented, the mechanisms underlying this activation are poorly
      understood. In this study we tried to elucidate whether the membrane phospholipid
      composition and physical state influence the activity of membrane-associated PLA2
      in ras-transformed fibroblasts. For this purpose membranes from non-transfected
      and ras-transfected NIH 3T3 fibroblasts were enriched with different
      phospholipids by the aid of partially purified lipid transfer protein. The
      results showed that of all tested phospholipids only phosphatidylcholine (PC)
      increased PLA2 activity in the control cells, whereas in their transformed
      counterparts both PC and phosphatidic acid (PA) induced such effect. Further we
      investigated whether the activatory effect was due only to the polar head of
      these phospholipids, or if it was also related to their acyl chain composition.
      The results demonstrated that the arachidonic acid-containing PC and PA molecules
      induced a more pronounced increase of membrane-associated PLA2 activity in ras
      transformed cells compared to the corresponding palmitate-stearate- or oleate-
      containing molecular species. However, we did not observe any specific effect of
      the phospholipid fatty acid composition in non-transformed NIH 3T3 fibroblasts.
      In ras-transformed cells incubated with increasing concentrations of arachidonic
      acid, PLA2 activity was altered in parallel with the changes of the cellular
      content of this fatty acid. The role of phosphatidic and arachidonic acids as
      specific activators of PLA2 in ras-transformed cells is discussed with respect to
      their possible role in the signal transduction pathways as well as in the
      processes of malignant transformation of cells.

PMID- 9924986
TI  - Glycosyl phosphatidylinositol (GPI)/inositolphosphate glycan (IPG): an
      intracellular signalling system involved in the control of thyroid cell
      proliferation.
AB  - In porcine thyrocytes, TSH alone does not induce cell growth. Recently, it has
      been demonstrated that acute stimulation by TSH of porcine thyrocytes leads to
      release an inositolphosphate glycan (IPG) described as a putative second
      messenger for various growth factors in different cell types. IPG isolated from
      porcine thyrocytes induces proliferation of fibroblasts EGFR T17 and porcine
      thyrocytes. In porcine thyrocytes we have confirmed that cell growth requires the
      presence of both TSH and insulin. This effect is reproduced by 8-bromo cyclic AMP
      suggesting a mediation by intracellular cyclic AMP. Cooperative effects between 8
      bromo cyclic AMP and IPG have also been evidenced and are in favour of a
      crosstalk between distinct signalling pathways.

PMID- 9924987
TI  - Effect of N-terminal deletions on the activity of pokeweed antiviral protein
      expressed in E. coli.
AB  - Pokeweed antiviral protein (PAP) from Phytolacca americana is a highly specific N
      glycosidase removing adenine residues (A4324 in 28S rRNA and A2660 in 23S rRNA)
      from intact ribosomes of both eukaryotes and prokaryotes. Due to the ribosome
      impairing activity the gene coding for mature PAP has not been expressed so far
      in bacteria whereas the full-length gene (coding for the mature 262 amino acids
      plus two signal peptides of 22 and 29 amino acids at both N- and C-termini,
      respectively) has been expressed in Escherichia coli. In order to determine: 1)
      the size of the N-terminal region of PAP which is required for toxicity to E.
      coli; and 2) the location of the putative enzymatic active site of PAP, 5'
      terminal progressive deletion of the PAP full-length gene was carried out and the
      truncated forms of the gene were cloned in a vector containing a strong
      constitutive promoter and a consensus Shine-Dalgarno ribosome binding site. The
      ribosome inactivation or toxicity of the PAP is used as a phenotype characterized
      by the absence of E. coli colonies, while the mutation of PAP open reading frames
      in the small number of survived clones is used as an indicator of the toxicity to
      E. coli cells. Results showed that the native full-length PAP gene was highly
      expressed and was not toxic to E. coli cells although in vitro ribosome
      inactivating activity assay indicated it was active. However, all of the N
      terminal truncated forms (removal of seven to 107 codons) of the PAP gene were
      toxic to E. coli cells and were mutated into either out of frame, early
      termination codon or inactive form of PAP (i.e., clone PAP delta107). Deletion of
      more than 123 codons restored the correct gene sequence but resulted in the loss
      of the antiviral and ribosome inactivating activities and by the formation of a
      large number of clones. These results suggest that full-length PAP (with N- and C
      terminal extensions) might be an inactive form of the enzyme in vivo presumably
      by inclusion body formation or other unknown mechanisms and is not toxic to E.
      coli cells. However, it is activated by at least seven codon deletions at the N
      terminus. Deletions from seven through to 107 amino acids were lethal to the
      cells and only mutated forms (inactive) of the gene were obtained. But deletion
      of more than 123 amino acids resulted in the loss of enzymatic activity and made
      it possible to express the correct PAP gene in E. coli. Because deletion of Tyr94
      and Val95, which are involved in the binding of the target adenine base, did not
      abolish the activity of PAP, it is concluded that the location previously
      proposed for PAP enzymatic active site should be reassessed.

PMID- 9924988
TI  - H-NMR and CD studies on the structural transition of serum albumin in the acidic
      region--the N-->F transition.
AB  - Helical content (f(alpha)) of bovine mercaptalbumin (BMA) showed the
      characteristic two-step decrease in the acidic region, one corresponding to the N
      ->F transition (pH 4.40-->3.75; f(alpha), 0.68-->0.58) and the other to the F-->E
      transition (the acid-expansion) (pH 3.60-->2.90; falpha, 0.58-->0.48). However,
      falpha of human serum albumin (HSA) mainly decreased in the N-->F transition (N-
      >F, pH 4.6-->3.4; falpha, 0.70-->-0.55 and F-->E, below pH 3.0; falpha, 0.55-
      >0.52). The difference in pH-profile of f(alpha) between BMA and HSA might be due
      to the microheterogeneity. The 1H-NMR spectra and cross-relaxation times (T(IS))
      from irradiated to observed protein protons, which reflect the structural
      fluctuation and/or mobilability in proteins, were measured on the N-, F-, E-forms
      of HSA and BMA, and the N*-form (8.23 M urea, neutral pD) of iodoacetamide
      blocked HSA (IA-HSA) and bovine serum albumin (IA-BSA). The 1H-NMR spectra and
      elongations of T(IS) values for the F- and E-forms of HSA and the E-form of BMA
      were quite similar to those for the N*-form of IA-HSA and IA-BSA, indicating the
      liberation of the intramolecular motion in the F- and E-forms. Those for the F
      form of BMA were intermediate between the N- and E-form. The present results
      together with the reported data on hydrodynamic radii and D-H exchange reaction,
      indicate that the F-form of HSA and presumably BMA has a native-like globule form
      with a highly helical state and fluctuating tertiary structure. Thus, all of the
      present findings on the F-form of serum albumin seem to be in accord with the
      structural features for the F-form suggested by Foster's group (1-3, 19, 20, 22,
      23) and the molten globule state demonstrated by Dolgikh et al. (40), and Ohgushi
      and Wada (36, 37).

PMID- 9924989
TI  - Solution conformations of deltorphin-I obtained from combined use of quantitative
      2D-NMR and energy calculations: a comparison with dermenkephalin.
AB  - Deltorphin-I, Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 and dermenkephalin, Tyr-D-Met-Phe
      His-Leu-Met-Asp-NH2, two highly related opioid peptides from frog skin, display
      very similar N-termini but strikingly different C-terminal tails. Nevertheless,
      both peptides are highly potent at, and exquisitely selective for the delta
      opioid receptor. To identify common determinants concuring to the remarkably
      efficient targeting of deltorphin-I and dermenkephalin, combined use of
      quantitative two-dimensional nuclear magnetic resonance (53 dipolar interactions
      studied at four temperatures) and energy calculations using simulated annealing
      generated five groups of deltorphin-I conformers. These groups were pooled into
      two families whose overall conformation could be described either by a left
      handed helix (Family I) or by a big loop (Family II), both stabilized by H-bonds.
      Proximity of D-Ala2-Phe3-Asp4 and Val5-Val6-Gly7 triads is an obvious structural
      similarity between almost all groups in both families of structures. Whereas
      differences between the two families originated mostly from a transition at psi
      Asp4 backbone dihedral angle, the backbone structures at segment 1-4 are similar
      and spatial arrangements of Tyr1 (t) and Phe3 (g-) are identical in one group of
      each family. Moreover, these two groups have a N-terminal tetrapeptide whose
      conformation most closely resembles that of a well-defined group of structures
      for dermenkephalin. Altogether, these results suggest that conformational
      attributes that are common to dermenkephalin and deltorphin-I, i.e., the backbone
      conformation of the N-terminal tetrapeptide and preferential orientations in the
      side-chain of Tyr1 (t) and Phe3 (g-) underlie their ability to bind with high
      selectivity to the delta-opioid receptor.

PMID- 9924991
TI  - Sequence-assisted peptide synthesis (SAPS).
AB  - In solid-phase peptide synthesis (SPPS) the growing peptide chain may undergo
      chain aggregation which can cause serious synthetic problems. A number of
      investigations concerning this problem have been reported in the chemical
      literature. During a study of such "difficult sequences" using the Fmoc
      protection strategy, we have observed that peptide-chain aggregation may be
      significantly reduced when certain amino acid sequences are incorporated C
      terminally (1). Thus, synthesis of the difficult poly-alanine, (Ala)n, sequence
      (n < or = 20) has been investigated with (Lys(Boc))m (m < or = 6) and (Glu(tBu))m
      (m > or = 6) as pre-sequences. With m > or = 3, peptides are obtained as single,
      homogeneous products while a complex mixture of deletion peptides and
      corresponding Fmoc-protected peptides is formed (n > or = 6) without the pre
      sequence. A mixed pre-sequence, (Lys(Boc)Glu(tBu))3, has a similar favorable
      effect on the synthetic results, but the positive effect seems confined to a
      rather narrow framework of amino acids and side-chain protecting groups in the
      pre-sequence as discussed in the article. Among other reputedly difficult
      sequences the synthesis of H-(Thr-Val)5-OH, H-Val-Asn-Val-Asn-Val-Gln-Val-Gln-Val
      Asp-OH, the Acyl Carrier Protein (65-74) and the human insulin B-chain has been
      investigated. In all cases introduction of a pre-sequence gives rise to
      satisfactory synthetic results. In the latter case, the lysine pre-sequence may
      be cleaved enzymatically to give the desB30 insulin B-chain. NIR-FT Raman studies
      of the synthesis of the poly-alanine, (Ala)n, sequences have shown that the pre
      sequence (Lys(Boc))6 shifts the conformation of the growing peptide chain from a
      beta-structure (n > or = 6) to a random coil conformation (1c). This result is in
      agreement with the general observation that SPPS proceeds optimally under random
      coil conditions.

PMID- 9924990
TI  - Reduced amide pseudopeptide analogues of a malaria peptide possess secondary
      structural elements responsible for induction of functional antibodies which
      react with native proteins expressed in Plasmodium falciparum erythrocyte stages.
AB  - A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time
      within the 1513 malaria peptide KEKMV motif to obtain a set of five
      pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide
      coded 1513, derived from the MSP-1 protein. This high-binding motif included in
      the 1513 peptide is involved in the attachment of the malarial parasite to human
      erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP
      HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance
      experiments allowed definition of the five pseudopeptide analogues' secondary
      structural features. Such structures are present in only a very few molecules in
      the 1513 parent peptide. A molecular model demonstrating the solution of the
      three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed
      on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated
      to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not
      only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic
      processing proteins but also different SPf(66)n malaria vaccine batches
      containing the native sequence. In addition, the mAbs were able to modify the
      kinetics of Plasmodium falciparum parasites' intraerythrocytic development and
      their ability to invade new RBCs. The presented evidence suggests that peptide
      bond-modified peptides could reproduce a transient state in 1513's native
      sequence and represent useful candidates in the development of a second
      generation of effective malarial vaccines.

PMID- 9924992
TI  - First record of host defence peptides in tadpoles. The magnificent tree frog
      Litoria splendida.
AB  - Tadpoles of the Magnificent Tree Frog Litoria splendida produce host defence
      peptides early in their development and well before metamorphosis. Peptides were
      identified and characterized using high performance liquid chromatography and
      electrospray mass spectrometry. No host defence peptides were identified in the
      eggs. The neuropeptide caerulein was detected 10 d after egg deposition, and the
      antibiotic peptides caerin 1.1, caerin 1.6 and caerin 3.1 first appeared at 14 d.
      The concentration of peptides increases with the onset of metamorphosis at 84 d,
      when the host-defence peptide profile is the same as that of the adult.

PMID- 9924993
TI  - Solid-phase synthesis, conformational analysis, and biological activity of AVR9
      elicitor peptides of the fungal tomato pathogen Cladosporium fulvum.
AB  - The race-specific peptide elicitor AVR9 of the fungal pathogen Cladosporium
      fulvum specifically induces a hypersensitive response in tomato genotypes
      carrying the complementary resistance gene Cf-9. The total chemical syntheses of
      this 28-residue AVR9 peptide containing three disulfide bonds, and of three
      mutant peptides [R8K]AVR9, [F10A]AVR9 and [F21A]AVR9, have been accomplished. The
      syntheses were carried out using a stepwise solid-phase approach based on tBoc
      chemistry. The disulfide bridges were formed by air oxidation. The correctness of
      the chemical structure of all folded synthetic peptides was confirmed by combined
      NMR and MS analyses. The biological activity and a number of physicochemical
      properties of folded synthetic AVR9 are identical to those of native fungal 28
      residue AVR9. The overall conformations of the folded synthetic mutant peptides
      were comparable to that of synthetic wild-type AVR9 as demonstrated by NMR
      spectroscopy. Mutant [R8K]AVR9 showed a threefold higher, and mutant [F10A]AVR9 a
      threefold lower necrosis-inducing activity when compared to synthetic wild-type
      AVR9. However, mutant [F21A]AVR9 showed hardly any necrosis-inducing activity.
      Affinity for polyclonal antibodies raised against native fungal AVR9 is
      positively correlated with the necrosis-inducing activity of the synthetic AVR9
      peptides ([R8K]AVR9 > wild-type AVR9 > [F10A]AVR9 > [F21A]AVR9).

PMID- 9924994
TI  - Detection of human antibodies using "convergent" combinatorial peptide libraries
      or "mixotopes" designed from a nonvariable antigen: application to the EBV viral
      capsid antigen p18.
AB  - We have previously described the use of synthetic combinatorial "convergent"
      libraries, or "mixotopes" as immunogens or as antigens to represent naturally
      hypervariable sequences. The success of this approach suggests that such a
      mixture of closely related peptides could, at least in part, conveniently
      represent a nonvariable epitope during its multiple interactions with an antibody
      population. To address this possibility, we have designed from a non-variable
      immunodominant peptide of the EBV-viral capsid antigen of 18 kD (VCAp18) a series
      of three mixotopes containing from 65,000 to 16 million combinatorial sequences.
      The reactivity of VCAp18 and its three derived mixotopes was examined in ELISA
      towards a collection of 74 human sera from documented EBV-negative or EBV
      positive donors, and analyzed in terms of sensitivity and specificity. Following
      the observation that the two least degenerated mixotopes could improve the
      sensitivity of detection of some sera of low reactivity for VCAp18, we decided to
      combine each mixotope with the VCAp18 peptide. In the case of the least
      degenerated mixotope in combination with VCAp18, sensitivity and specificity for
      immunoenzymatic EBV-serodiagnosis, were enhanced to 100%. Our results suggest
      that synthetic "convergent" combinatorial peptide libraries or "mixotopes,"
      designed from nonvariable antigens, could be useful adjuncts to an antigenic
      single-sequence peptide in immunoenzymatic serodiagnosis.

PMID- 9924995
TI  - Aggregation of A beta Alzheimer's disease-related peptide studied by dynamic
      light scattering.
AB  - The aggregation behavior of the major component of Alzheimer's disease-related,
      amyloid peptides, Abeta-(1-40) and Abeta-(1-42), was studied in solution using
      dynamic light scattering. With most solvents employed, we found fibrils
      coexisting with oligomeric Abeta species. Pronounced differences were observed in
      aggregation of Abeta-(1-40) and (1-42) sequences in acetonitrile-water mixtures.
      Cofactors such as Zn2+ were found to induce deaggregation of Abeta instead of
      aggregation. The results indicated that the initial state of the peptide
      immediately after synthesis is rather poorly defined. Using freezing instead of
      lyophilization after the final peptide synthesis step, may partially relieve
      these problems.

PMID- 9924996
TI  - Carboxy-terminal extension stabilizes the topological stereoisomers of guanylin.
AB  - The peptide hormone guanylin constitutes two topological stereoisomers, which are
      connected through an equilibrium of interconversion. To investigate the
      importance of amino acid residues in the central region between the inner
      cysteines and at the carboxy terminus for this isomerism, synthetic derivatives
      of guanylin were compared by HPLC, 2D1H NMR spectroscopy and by their guanylyl
      cyclase-C (GC-C)-activating potency. An increase in the central sterical bulk by
      introduction of diiodo-Tyr9 had virtually no effect on the isomerization
      kinetics. Compared to guanylin, carboxy-terminal amidation did not affect the
      equilibrium between the two isoforms either. In contrast, two significantly
      stabilized isomers were obtained by extending the carboxy terminus of guanylin
      with one additional leucine resembling the characteristic of human uroguanylin
      isomers. This effect was intensified by a further Lys-Lys extension, thus
      revealing that the conformational exchange between the guanylin isomers is
      dependent on the extent of the sterical hindrance in the carboxy-terminal region
      of this peptide. Demonstrated by 2D NMR spectroscopy, the separated isomers of
      the carboxy-terminally extended derivatives of guanylin exhibit unambiguously
      closely related structures as found originally for guanylin isomers, which are
      only detectable as a mixture. Because only one of the stabilized guanylin isomers
      activates guanylyl cyclase-C, the three-dimensional structure of the GC-C
      activating guanylin isomer is now defined. The stabilized isoforms of guanylin
      described in this study represent suitable tools for the separate functional
      investigation of the GC-C-agonistic isomer of guanylin as well as of its isomeric
      counterpart.

PMID- 9924997
TI  - Screening of combinatorial peptide libraries: identification of ligands for
      affinity purification of proteins using a radiological approach.
AB  - Peptides deduced from peptide libraries may serve as affinity ligands for protein
      purification. Identification of a ligand that binds the protein of interest
      depends highly on the screening method used. One approach which offers simple and
      direct detection involves screening a solid-phase peptide library against a
      radiolabeled target protein. We have developed a radiological screening method,
      using 14C as a radioactive label, that offers high resolution and sensitivity.
      Less than 100 DPM/bead are detectable after a one-day exposure using
      autoradiography. The validity of the technique was illustrated by screening a
      solid-phase hexameric-peptide library spiked with YNFEVL-beads against 14C
      labeled ribonuclease S-protein. For this particular system, the amount of protein
      bound to a single bead was estimated to be in the femtomolar range with a
      peptide:protein ratio of 500:1. Finally, a portion of the library was screened
      against 14C-labeled fibrinogen. Three peptides deduced from the library, WQEHYN,
      WQETYQ, and YENYGY, purified fibrinogen from a mixture with albumin.

PMID- 9924999
TI  - Interference pattern in the urethral sphincter: a quantitative electromyographic
      study in patients before and after radical retropubic prostatectomy.
AB  - OBJECTIVE: Radical retropubic prostatectomy (RRP) involves removal of the bladder
      neck where the proximal urethral sphincter is located. Assuming that this
      sphincter participates in urinary continence mechanisms, removal of this
      sphincter might increase the interference pattern in the distal urethral
      sphincter as a compensatory mechanism. MATERIAL AND METHODS: We examined the
      distal (striated) urethral sphincter before and after surgery with quantitative
      EMG techniques in ten patients. RESULTS: No compensatory activity was
      demonstrated, but tendencies towards a decreased number of turns at rest (41 pre
      op/27 post-op) and an increased mean amplitude at maximal activation (334 microV
      pre-op/408 microV post-op) in the interference pattern in the muscle were
      recorded using the turns/amplitude (T/A) analysis. The fibre density was 1.71
      before and 1.96 after surgery (p = 0.08), indicating a peripheral nerve lesion.
      CONCLUSIONS: The numerical reduction of turns during rest can be explained by
      disturbed feedback, indicating that not only efferent, but also sensory afferent
      nerve fibres can be involved in an iatrogen lesion during prostatic surgery. The
      increased mean amplitude at maximal activation was probably due to reinnervated
      motor units with increased amplitudes.

PMID- 9924998
TI  - Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference
      values in screening for prostate cancer--a study of a randomly selected
      population of 2,400 men.
AB  - Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400
      randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with
      prostate cancer were diagnosed. The PSA results were correlated to the diagnosis,
      the men's age, and the prostate volume. Least square regression analysis was used
      to calculate the 95% upper confidence intervals for PSA in each year of age in
      men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii)
      PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A
      significant correlation was found between PSA and prostate volume, between PSA
      and age, and between the prostate volume and age. The calculated annual growth of
      the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted
      upper PSA reference values for the three age categories studied (55-59, 60-64 and
      65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4
      ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were
      17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the
      PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA
      cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The
      median PSA values and median prostate volumes calculated for men with benign
      findings may serve as a reference in future studies.

PMID- 9925000
TI  - Autotransfusion supported by erythropoietin therapy in transurethral resection of
      the prostate.
AB  - We investigated the collection and transfusion of autologous blood after
      treatment with EPO in 68 BPH patients (including 10 controls) who were scheduled
      to undergo TUR-P. All patients received oral and/or intravenous iron supplements.
      Assessments were made based on the preoperative increase in blood hemoglobin
      levels including autologous blood predonation (deltaHb). The deltaHb in patients
      undergoing collection of 600 ml of blood were as follows: control group: -0.36 +/
      0.57 g/dl; EPO group, 9 x 3000 units intravenously: 1.15 +/- 0.83 g/dl; EPO
      group, 6 x 6000 units intravenously: 0.79 +/- 0.80 g/dl; EPO group, 3 x 12,000
      units subcutaneously: 1.47 +/- 0.62 g/dl. In patients undergoing collection of
      800 ml of blood, the results were as follows: EPO group, 3 x 12,000 units
      subcutaneously: 1.80 +/- 0.69 g/dl; EPO group, 3 x 24,000 units subcutaneously:
      2.03 +/- 0.77 g/dl. All EPO-treated patients successfully underwent surgery using
      their own blood, and none of them required homologous transfusion. The increase
      of Hb was greater in the patients treated with EPO than in controls, allowing
      safe preoperative blood collection even in elderly patients. In patients with
      relatively severe BPH, homologous transfusion could be avoided and surgery was
      performed safely.

PMID- 9925002
TI  - Increased prevalence of urinary tract infections and anomalies in infants with
      pyloric stenosis.
AB  - We performed a retrospective analysis of all patients admitted to our institution
      with a diagnosis of infantile hypertrophic pyloric stenosis (IHPS) during a 10
      year period from 1985-95 in order to assess the possible association between IHPS
      and urinary tract infections (UTIs). All 285 patients with IHPS had radiological
      or ultrasonographic confirmation of that diagnosis and underwent the Ramstedt
      procedure. Those who continued to be symptomatic were evaluated for UTI by urine
      analysis and culture. Positive cases were further evaluated for urinary system
      anomalies. The male:female ratio of IHPS was 3.4:1. Concomitant UTI was diagnosed
      in 8 patients by suprapubic aspiration or bladder catheterization. The prevalence
      of UTI in this series was 2.8%, 20-fold higher than the expected prevalence.
      Three of the 8 patients with UTI (37.5%) had urinary tract anomalies. These
      findings suggest an association between IHPS and UTI. We recommend that all IHPS
      patients be evaluated for UTI and positive cases undergo further evaluation for
      urinary anomalies.

PMID- 9925001
TI  - The higher injury risk of abnormal kidneys in blunt renal trauma.
AB  - OBJECTIVE: To investigate the vulnerability of abnormal kidneys in blunt trauma,
      and to determine clinical features which enable identification of patients at
      risk of renal abnormality, hence modifying their management. MATERIAL AND
      METHODS: The medical records of 120 patients with blunt renal trauma were
      reviewed. Presence of pre-existing renal abnormalities, clinical symptoms,
      contrast study findings, associated injuries and the estimated impact velocity
      were recorded. RESULTS: Pre-existing renal abnormalities were found in 23
      patients (19%). Patients with renal abnormalities had a lower rate of associated
      trauma to other abdominal organs, a lower Injury Severity Score (ISS) and their
      kidneys were more frequently injured by low velocity impacts. Of the patients
      with normal kidneys requiring surgery, hemodynamics and/or severity of the renal
      lesions triggered the operative indications in all cases, whereas most (57%) of
      the abnormal kidneys were operated because of their underlying renal pathology.
      CONCLUSION: Patients at risk for harbouring renal pathology are characterized by
      the association of monotrauma, macroscopic hematuria and low impact velocity. In
      this clinical setting, contrast studies should be generously indicated, since the
      management of abnormal kidneys unmasked by trauma is, to a large extent,
      dependent on the type of pathology.

PMID- 9925003
TI  - Decreased levels of S-100 protein in non-ulcer interstitial cystitis.
AB  - Interstitial cystitis (IC) is a chronic debilitating condition which mainly
      affects women. Accumulated evidence indicates that IC is a heterogeneous
      syndrome. As compared to classic IC, the non-ulcer type of IC appears to be
      different concerning symptomatic, endoscopical and histological findings, as well
      as in response to various forms of treatment. S-100 is a neural protein
      considered to be located primarily in the axons. To explore further the
      neurogenic nature of the disease, we compared bladder wall S-100 content in
      controls and in patients with classic and non-ulcer IC. We noticed a decrease in
      S-100 content in non-ulcer IC as compared to controls. This may be an expression
      of altered peripheral innervation in non-ulcer IC, which, in turn, may be an
      indication of primary neurogenic etiology. The difference in S-100 content
      between classic and non-ulcer IC supports the hypothesis that they represent
      separate entities, which may explain differences in response to various
      treatments.

PMID- 9925004
TI  - Prevalence of positive urinary dipstick analysis (leucocyte esterase, nitrite,
      haemoglobin, or glucose) in a population of 3645 adult subjects--consequence for
      measurement of urinary albumin excretion rate.
AB  - OBJECTIVES: To assess prevalence of positive urinary dipstick analysis for
      leucocyte esterase, nitrite, haemoglobin, or glucose in the general population
      and measure the urinary albumin excretion rate (UAER) in subjects with or without
      a positive dipstick analysis. DESIGN: A cross-sectional study of 3645 subjects.
      SETTING: An unselected urban population study. MAIN OUTCOME MEASURES: Prevalence
      data of positive dipstick analyses and UAER values. RESULTS: Prevalence data of a
      positive dipstick analysis were 12%, 4%, 3% and 6%, respectively, for leucocyte
      esterase, nitrite, haemoglobin, and glucose. Subjects with any positive dipstick
      analysis had significantly higher UAER than subjects with a negative analysis:
      4.9 (4.4-5.3) (geometric mean (95% confidence interval)) vs 3.0 (2.9-3.1) mg 24
      h(-1) (p < 0.001). CONCLUSIONS: Prevalence data of positive urinary dipstick
      analyses in a large population based study are provided. Subjects with any
      positive finding had higher UAER than controls. Exclusion of subjects with a
      positive finding is recommended in studies of UAER as a cardiovascular risk
      factor in non-diabetic subjects.

PMID- 9925005
TI  - Peritoneal dialysis access: a comparison of peritoneoscopic and surgical
      insertion techniques.
AB  - Prospectively collected data were analysed comparing 108 consecutive
      peritoneoscopically (n = 65) and surgically (n = 43) placed peritoneal dialysis
      catheters during a three-year period. Catheter-linked mechanical complications
      occurred more often in the peritoneoscopical group, and pericatheteral leakage
      ended in catheter loss in 13.8%. Overall probability of catheter survival in the
      peritoneoscopic group at 12, 24 and 36 months was 73%, 56% and 24%, and in the
      surgical group 87%, 87% and 66%, respectively (p < 0.05). Rates of infectious
      complications, peritonitis and exit site infections were similar.

PMID- 9925006
TI  - Prevesical and inguinal abscess following intravesical BCG instillation.
AB  - Many complications have been described, both local and systemic, with
      intravesical BCG in the treatment and prophylaxis of superficial bladder
      carcinoma. The case discussed herein is a pelvic and inguinal abscess after BCG
      instillation for high-grade superficial bladder cancer.

PMID- 9925007
TI  - Internal jugular vein haemodialysis catheter-induced right atrium endocarditis-
      case report and review of the literature.
AB  - We present a case of right-sided endocarditis as a life-threatening complication
      of having a jugular vein haemodialysis catheter inadvertently placed in the right
      atrium. The mechanisms of direct traumatization of the endocardium by the
      catheter tip and continuous inoculation of bacteria onto the endocardial surface
      make dual lumen catheter-induced endocarditis similar to the pathophysiology of
      experimental endocarditis in animals. Therefore, the catheter tip should be
      placed in the distal superior vena cava during cannulation. Once endocarditis is
      present, removal of catheters and a 4-6-week course of intravenous antibiotics
      guided by the sensitivity test are recommended.

PMID- 9925008
TI  - Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant
      recipient treated with cyclosporine A.
AB  - Since cyclosporine A (CsA) had been used in renal transplant recipients,
      important improvements in short-term and long-term graft survivals have been
      detected. In spite of these improvements CsA seems to have several adverse
      effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other
      organs and systems (skin, liver, nervous system, etc.) and causes, increased
      risks of infections and malignancies. Hypomagnesemia is one of the side effects
      of CsA therapy, but it is a rare condition in living related donor renal
      transplant recipients. It may also cause multi-system dysfunction, especially
      hypocalcemia and hypokalemia, which cannot be corrected without magnesium
      therapy. In addition, rhabdomyolysis was detected in animals, but it has not been
      reported in living related donor renal transplant recipients. In this case
      report, a living related donor renal transplant recipient who suffered from
      hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and
      discussed.

PMID- 9925009
TI  - Splenunculus mimicking late local recurrence of renal cell carcinoma.
AB  - We report on a case of a splenunculus found in the renal fossa 14 years after
      left transperitoneal radical nephrectomy and splenectomy for renal cell
      carcinoma. The significance of splenunculi in differential diagnosis of space
      occupying lesions in the left renal bed is discussed.

PMID- 9925010
TI  - Leiomyoma of the urinary bladder causing tamponade.
AB  - Benign mesenchymal tumours of the bladder are rare, accounting for only 1-5% of
      bladder neoplasms. We describe what appears to be the first reported case of
      massive bleeding from a leiomyoma of the urinary bladder causing tamponade
      requiring emergency surgery.

PMID- 9925012
TI  - The tip link's role in asymmetric stereocilia motion of chick cochlear hair
      cells.
AB  - The symmetry of chick cochlear hair bundle motion was examined in this study.
      Isolated segments from the basilar papilla were incubated in vitro in either
      normal or low calcium medium, which is known to disrupt tip links. Stereociliary
      bundles, stimulated with an oscillating water microjet, were oriented in profile
      and viewed in slow motion at high magnification with stroboscopic illumination.
      The displacement of the tallest hair in the bundle was fixed to 20 degrees peak
      to-peak (P-P) motion. The angular deflections of the shortest and tallest hairs
      were then measured in both the positive (towards the tallest hair) and negative
      (towards the shortest) directions with respect to the non-stimulated position of
      the hair. The tallest hairs exhibited nearly symmetric motion in medium
      containing normal and low calcium. The shortest hairs, in normal calcium,
      displayed considerable asymmetry with angular deflections in the positive
      direction significantly larger than in the negative direction. This asymmetric
      motion disappeared after incubation in low calcium. The shortest hair angular
      displacement in the negative direction, however, was the same in both normal and
      low calcium conditions. These results indicated that the tallest and shortest
      hairs moved with equal angular deflection in the negative direction, while in the
      positive direction the shortest hair moved through a significantly greater
      angular deflection than the tallest hair. The implication of this finding is that
      the tip links contributed significantly to hair bundle motion in the positive
      direction only.

PMID- 9925011
TI  - Postnatal development of the organ of Corti in cats: a light microscopic
      morphometric study.
AB  - This study quantitatively characterizes the development of the major
      morphological features of the organ of Corti during the first 2 weeks postnatal,
      the period when the cat auditory system makes the transition from being
      essentially non-functional to having nearly adult-like responses. Four groups of
      kittens (n = 3) were studied at one day postnatal (P1), P5, P10, P15, and
      compared to adults. Measurements were made of the organ of Corti at 3 cochlear
      locations: 20%, 60% and 85% of basilar membrane length from the base cochlear
      locations which in the adult correspond to best frequencies of approximately 20
      kHz, 2 kHz and 500 Hz, respectively. In addition, measurements of basilar
      membrane length and opening of the tunnel of Corti were made in 20 cochlear
      specimens from kittens aged P0-P6. Results indicate that: (i) at P0 the basilar
      membrane has attained adult length, and the tunnel of Corti is open over
      approximately the basal one-half of the cochlea; (ii) the initial opening of the
      tunnel of Corti occurs at a site about 4 mm from the cochlear base (best
      frequency of approximately 25 kHz in the adult cochlea); (iii) the thickness of
      the tympanic cell layer decreases markedly at the basal 20-kHz location; (iv) the
      areas of the tunnel of Corti and space of Nuel and the angulation of the inner
      hair cells (IHC) relative to the basilar membrane all show marked postnatal
      increases at both the middle and apical locations; (v) IHC are nearly adult-like
      in length and shape at birth, whereas the OHC (at 2-kHz and 500-Hz locations)
      undergo marked postnatal changes; (vi) disappearance of the marginal pillars and
      maturation of the supporting cells are not yet complete by P15.

PMID- 9925013
TI  - Distal separation of chick cochlear hair cell stereocilia: analysis of contact
      constraint models.
AB  - One model often used in the study of hair bundle micromechanics assumes simple
      geometric relationships between hair displacements, constrained by contact
      between neighboring hairs at their distal tips. Recent observations of hair
      bundle motion provided the opportunity to evaluate the contact-constraint model
      against measured displacements for the tallest and shortest sensory hairs. A
      contact-constraint model was developed based on the geometry of a single column
      of stereocilia. The model used morphological data from chick hair bundles for
      which displacement data in the excitatory and inhibitory directions were also
      available. For each hair bundle, a unique sensory hair radius was determined so
      that the calculated resting bundle morphology matched the measured values. The
      model was then evaluated against the displacement data for each hair bundle. In
      each case, the model underestimated the excitatory displacement of the shortest
      hairs. Failure of the model to accurately predict bundle motion raises the
      possibility of a distal separation between the hairs at rest. It is suggested
      that tip links pull the hairs through this separation during excitatory
      deflections. Perhaps at damaging levels of displacement, the hairs suddenly come
      into contact, tip-link tension dramatically increases, and the tip-links are
      fractured.

PMID- 9925014
TI  - Acquired resistance to acoustic trauma by sound conditioning is primarily
      mediated by changes restricted to the cochlea, not by systemic responses.
AB  - Hearing loss caused by intense sound exposure can be significantly reduced by pre
      exposing subjects to moderate-level acoustic stimuli. This phenomenon occurs in a
      variety of mammals. We investigated whether sound conditioning provides acquired
      resistance to acoustic trauma through local mechanisms selectively in the
      conditioned ears or if systemic mechanisms are involved that would yield
      contralateral protection in unconditioned ears. Guinea pigs (group I) in which
      one external ear canal was occluded were exposed to conditioning sound (2-20 kHz,
      85 dB SPL, 5 h/day, 10 days). After removing the occlusion, the animals were then
      subjected bilaterally to intense noise (2-20 kHz, 110 dB SPL, 5 h) 5 days after
      the last conditioning exposure. Animals without ear canal occlusion were also
      exposed to the intense sound without conditioning (group II) or following the
      same conditioning exposure (group III). Intense sound exposure caused
      significantly greater permanent ABR threshold shifts at all frequencies tested
      (4, 8, 12, 16 and 20 kHz) in group II than in group III. In group I, the occluded
      ears showed significantly greater threshold shifts at all frequencies compared to
      the unoccluded ears. The threshold shifts in the occluded ears in group I were
      identical to those observed in group II; and the shifts in unoccluded ears in
      group I were identical to those in group III. Protective effects provided by
      sound conditioning were almost the same in group III and in the unoccluded ears
      in group I. The extent of hair cell damage supported the physiological findings.
      These results indicate that acquired resistance to acoustic trauma provided by
      sound conditioning is restricted to the cochlea exposed to conditioning sound,
      suggesting that conditioning protection is mediated primarily by the changes that
      occur locally within the conditioned cochlea. This animal model, with unilateral
      external ear canal occlusion during sound conditioning, is useful for studies of
      the mechanisms of conditioning protection.

PMID- 9925015
TI  - Adjustable frequency selectivity of auditory forebrain neurons recorded in a
      freely moving songbird via radiotelemetry.
AB  - One of the hearing system's basic properties that determines the detection of
      signals is its frequency selectivity. In the natural environment, a songbird may
      achieve an improved detection ability if the neuronal filters of its auditory
      system could be sharpened to adapt to the spectrum of the background noise. To
      address this issue, we studied 35 multi-unit clusters in the input layer of the
      primary auditory forebrain of nine European starlings (Sturnus vulgaris).
      Microelectrodes were chronically implanted in this songbird's cortex analogue and
      the neuronal activity was transmitted from unrestrained birds via a miniature FM
      transmitter. Frequency tuning curves (FTCs) and inhibitory sidebands were
      determined by presenting a matrix of frequency-level combinations of pure tones.
      From each FTC, the characteristic frequency (CF) and several parameters
      describing the neurons' filter characteristics were derived and compared to the
      same recording site's filter function while simultaneously stimulating with a
      continuous CF tone 20 dB above the response threshold. Our results show a
      significant improvement of frequency selectivity during two-tone stimulation,
      indicating that spectral filtering in the starling's auditory forebrain depends
      on the acoustic background in which a signal is presented. Moreover, frequency
      selectivity was found to be a function of the time over which the stimulus
      persisted, since FTCs were much sharper and inhibitory sidebands were largely
      expanded several milliseconds after response onset. Neuronal filter bandwidths
      during two-tone stimulation in the auditory forebrain are in good agreement with
      psychoacoustically measured critical bandwidths in the same species.
      Radiotelemetry proved to be a powerful tool in studying neuronal activity in
      freely behaving birds.

PMID- 9925017
TI  - Breed differences in deafferentation-induced neuronal cell death and shrinkage in
      chick cochlear nucleus.
AB  - Removal of functional presynaptic input can result in a variety of changes in
      postsynaptic neurons in the central nervous system, including altered metabolism,
      changes in neuronal cell size, and even death of the postsynaptic cell. Age
      dependent neuronal cell death and shrinkage has been documented in second order
      auditory neurons in the chick brainstem (nucleus magnocellularis, NM) following
      cochlea removal (Born and Rubel, 1985. J. Comp. Neurol. 231, 435-445). Here we
      examined whether the extent of neuronal cell death and shrinkage is also breed
      dependent. We performed unilateral cochlea removal on both hatchling and adult
      birds of either a broiler breed (Arbor Acres Cross) or egg layer breed (Hy-Line,
      H and N) and killed birds one week later. Changes in neuronal cell number and
      cross sectional area were determined from Nissl-stained sections. We observed 25%
      neuronal cell loss and a 15-20% decrease in neuronal cross sectional area after
      cochlea removal in either broiler or egg layer hatchling birds. In adult birds,
      however, neuronal cell loss is breed-dependent. Adult egg layer birds lose an
      average of 37% of NM neurons after cochlea removal, while adult broiler birds
      show no cell loss. In both breeds of adult birds, cochlea removal results in a
      20% decrease in neuronal cross sectional area. These results suggest that
      analysis of differences between breeds as well as ages of birds will prove
      fruitful in determining how afferent input controls neuronal survival and
      metabolism.

PMID- 9925016
TI  - Modulation of cochlear blood flow by extracellular purines.
AB  - Humoral adenosine 5'-triphosphate (ATP), adenosine and uridine 5'-triphosphate
      (UTP) have been shown to have a role in controlling local blood flow in a variety
      of tissues. The presence of P1 and P2 receptors in the cochlea, and particularly
      the highly vascular region, the stria vascularis, implies a vasoactive role for
      these compounds in the inner ear. To test the effect of extracellular purines and
      pyrimidines on cochlear blood flow, cochleae from anaesthetised guinea-pigs were
      perfused with ATP (1 microM-10 mM), adenosine (1 microM-10 mM) and UTP (1 mM) in
      artificial perilymph while blood flow through the cochlea was measured. An acute
      perilymphatic perfusion technique was established via tubing placed through a
      hole in the bone overlying scala tympani of the first cochlear turn, with an
      outlet hole in scala vestibuli of the fourth turn. Blood flow was measured by
      placing the probe of a laser Doppler blood perfusion monitor on the bone
      overlying the stria vascularis in the third cochlear turn. ATP and adenosine
      produced a significant dose dependent increase in cochlear blood flow (28.8
      229.0% and 35.8-258.1%, respectively). The effect of ATP (100 microM) on cochlear
      blood flow was reduced in the presence of reactive blue 2 (1 mM) and
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (1 mM). The blood flow
      response to adenosine (10 microM) was reduced in the presence of 1,3
      dimethylxanthine (theophylline, 100 microM), but not with either 3,7-dimethyl-1
      propargylxanthine (10 microM) or 8-cyclopentyl-1,3-dipropylxanthine (10 microM).
      UTP did not produce any change in the cochlear blood flow. To determine if the
      ATP effect was also mediated by adenosine derived from ectonucleotidase activity,
      the perilymphatic compartment was perfused with either ATP plus theophylline (100
      microM) or with the non-metabolisable form of ATP, adenosine 5'-O-(3
      thiophosphate) (ATPgammaS, 100 microM). The effect of ATP on cochlear blood flow
      was unaffected with the inclusion of theophylline while ATPgammaS produced an
      increase in cochlear blood flow similar to the one observed with ATP. These
      findings indicate that extracellular ATP and its metabolite adenosine have a
      modulatory role in cochlear blood flow possibly mediated by both P1 and P2
      receptors.

PMID- 9925018
TI  - Modulation of frequency selectivity by Na+- and K+-conductances in neurons of
      auditory thalamus.
AB  - In thalamic neurons, frequency-filter properties arise from intrinsic membrane
      properties which transform sensory inputs to thalamocortical signals. They also
      contribute to the tendency for the membrane to generate synchronized
      oscillations. We studied the frequency selectivities of thalamocortical neurons
      in the rat ventral medial geniculate body (MGBv) in vitro, using whole-cell
      recording techniques, sinewave (swept 'ZAP' or single) current inputs and
      pharmacological blockade of membrane currents. In a voltage range that was
      subthreshold to spike genesis, the frequency responses below 20 Hz were voltage
      dependent, they exhibited lowpass characteristics at depolarized potentials and
      bandpass resonance (near 1 Hz) in the activation range (approximately -65 to -50
      mV) of the low-threshold Ca2+-current (I(T)). A temperature increase of > 10
      degrees C in 3 neurons did not change this voltage-dependence and increased the
      frequency of maximum resonance to 2 Hz. The removal of extracellular Ca2+, its
      equimolar substitution with Mg2+ or blockade of I(T) with Ni2+ (0.5 mM)
      completely blocked the resonance at hyperpolarized potentials or rest, as well as
      the low-threshold Ca2+-spike (LTS). Blockade of high threshold Ca2+-currents with
      Cd2+ (50 microM) did not affect the resonance. These data implied that, like the
      LTS, an activation of I(T) produced the membrane resonance. An increased ZAP
      current input evoked action potentials near the resonant frequency as well as
      Cd2+-sensitive high-threshold Ca2+-spikes at depolarized membrane potentials and
      very low frequencies. By blocking a persistent Na+-current (I(NaP)), tetrodotoxin
      (300 nM) reduced the magnitude of the frequency response without affecting the
      frequency preference. The response was larger in amplitude, especially at
      frequencies lower than the maximum resonant frequency, when we used 4
      aminopyridine (0.05-0.1 and 1-2 mM), Ba2+ (0.2 mM) or Cs+ (3 mM) to block voltage
      dependent K+-currents. From these data, we suggest that A-type (I(A) and I(As))
      and inwardly rectifying (I(KIR)) K+-currents modulate resonance, changing the
      quality of the lowpass filter function. We conclude that the generation of
      membrane resonance in MGBv neurons depends critically on I(T)-activation while
      the quality of the frequency response is subject to modulation by voltage
      dependent conductances. The frequency selectivities in MGBv may contribute to
      lowpass filter functions for auditory transmission during wakefulness and
      oscillations observed during sleep.

PMID- 9925019
TI  - Auditory brainstem response forward-masking recovery functions in older humans
      with normal hearing.
AB  - We investigated the auditory brainstem response (ABR) recovery from forward
      masking using toneburst maskers and probes. Two subject groups matched for
      hearing thresholds were evaluated: normal-hearing young adults (21-40 years) and
      older subjects (63-77 years) with normal audiometric thresholds. Stimuli
      consisted of 1, 4 and 8 kHz tonebursts, with 2-4 cycle rise/fall time and no
      plateau. Forward maskers were tonebursts of the same frequency, with a 5 ms
      rise/fall time and a 20 ms plateau time. Probes were presented at 40 dB above
      threshold, and the forward masker was adjusted to a level that just eliminated
      the ABR to the 40 dB sensation level toneburst when the probe onset occurred at
      masker offset. Forward-masker intervals varied from 2 to 64 ms. ABR wave V
      latencies were similar for the young and old age groups regardless of toneburst
      frequency. Under forward-masking conditions, wave V latency was prolonged for the
      shorter intervals, and recovered to baseline latency by 64 ms. The forward-masker
      recovery functions were nearly identical for the two age groups for the 1 kHz
      toneburst. In contrast, there were clear differences in the recovery functions
      for the two age groups for the 4 and 8 kHz tonebursts. Specifically, the mean
      latency shift was greater for the aged group for forward-masker intervals of 16
      ms or less. The two age groups showed identical latency shifts for longer forward
      masker intervals. These data demonstrate prolonged recovery from forward masking
      in older human subjects. As these subjects had audiometric thresholds within
      normal limits, one plausible interpretation of this finding is that the prolonged
      recovery time is a manifestation of an aging effect on the central auditory
      nervous system rather than the periphery.

PMID- 9925020
TI  - Expression of membrane-bound and cytosolic guanylyl cyclases in the rat inner
      ear.
AB  - Membrane-bound guanylyl cyclases (GCs) are peptide hormone receptors whereas the
      cytosolic isoforms are receptors for nitric oxide. In the inner ear, the membrane
      bound GCs may be involved in the regulation of fluid homeostasis and the
      cytosolic forms possibly play a role in signal processing and regulation of local
      blood flow. In this comprehensive study, we examined, qualitatively and
      quantitatively, the transcription pattern of all known GC isoforms in the inner
      ear from rat by RT-PCR. The tissues used were endolymphatic sac, stria
      vascularis, organ of Corti, organ of Corti outer hair cells, cochlear nerve,
      Reissner's membrane, vestibular dark cells, and vestibular sensory cells. We show
      that multiple particulate (GC-A, GC-B, GC-D, GC-E, GC-F and GC-G) and several
      subunits of the heterodimeric cytosolic GCs (alpha1, alpha2, beta1 and beta2) are
      expressed, albeit at highly different levels. GC-C was not found. GC-A and the
      soluble subunits alpha1 and beta1 were transcribed ubiquitously. GC-B was present
      in all tissues except stria vascularis, which contained GC-A and traces of GC-E
      and GC-G. GC-B was by far the predominant membrane-bound isoform in the organ of
      Corti (86%), Reissner's membrane (75%) and the vestibulum (80%). Surprisingly, GC
      E, a retinal isoform, was detected in significant amounts in the cochlear nerve
      (8%) and in the organ of Corti (4%). Although the cytosolic GC is a heterodimer
      composed of an alpha and a beta subunit, the mRNA transcription of these subunits
      was not stoichiometric. Particularly in the vestibulum, the transcription of the
      beta1 subunits was at least four-fold higher than of the alpha1 subunit. The data
      are compatible with earlier suggestions that membrane receptor GCs may be
      involved in the control of inner ear electrolyte and fluid composition whereas NO
      stimulated GC isoforms mainly participate in the regulation of blood flow and
      supporting cell physiology.

PMID- 9925021
TI  - Age-related changes in [3H]strychnine binding in the vestibular nuclei of rats.
AB  - Glycine plays an important role as a neurotransmitter in the four vestibular
      nuclei (VN). The objective of this study was to determine if the levels of
      glycine-receptor binding in the VN change as a function of age. Quantitative
      receptor autoradiography was performed on brainstem sections from three age
      groups (3, 18 and 26 months) of Fischer 344 rats to assess binding in the VN.
      Glycine receptors were localized using [3H]strychnine binding. Strychnine binding
      declined monotonically with increasing age, such that the level of strychnine
      binding in each of the VN in the 28-month-old animals was approximately one-half
      that in the 3-month-olds. The age-related decrease in levels of strychnine
      binding suggest altered glycinergic function in the VN, which may in turn
      contribute to disturbances in equilibrium observed in the elderly.

PMID- 9925022
TI  - Pseudospontaneous activity: stochastic independence of auditory nerve fibers with
      electrical stimulation.
AB  - We describe a novel signal processing strategy for cochlear implants designed to
      emphasize stochastic independence across the excited neural population. The
      strategy is based on the observation that high rate pulse trains may produce
      random spike patterns in auditory nerve fibers that are statistically similar to
      those produced by spontaneous activity in the normal cochlea. We call this
      activity 'pseudospontaneous'. A supercomputer-based computational model of a
      population of auditory nerve fibers suggests that different average rates of
      pseudospontaneous activity can be created by varying the stimulus current of a
      fixed-amplitude, high-rate pulse train, e.g. 5000 pps. Electrically-evoked
      compound action potentials recorded in a human cochlear implant subject are
      consistent with the hypothesis that such a stimulus can desynchronize the fiber
      population. This desynchronization may enhance neural representation of temporal
      detail and dynamic range with a cochlear implant and eliminate a major difference
      between acoustic and electric hearing.

PMID- 9925023
TI  - Changes in distortion product otoacoustic emissions during prolonged noise
      exposure.
AB  - The aim of this study was to evaluate the reduction in 2f1-f2 distortion product
      otoacoustic emission (DPOAE) amplitude resulting from prolonged noise exposures.
      A group of five chinchillas was exposed continuously to an octave-band noise
      centered at 4.0 kHz for a total of 42 days, 6 days at each of seven exposure
      levels. Exposure level increased in 8-dB steps from 48 to 96 dB SPL. DPOAE input
      output (I/O) functions were measured at octave intervals over a range of primary
      tone f2 frequencies between 1.2 and 9.6 kHz. Measurements were obtained (1) pre
      exposure, (2) during days 3-6 of each 6-day exposure, and (3) 4 weeks after the
      final exposure. Continuous noise exposure caused a reduction in DPOAE amplitude
      that was greatest at f2 frequencies within and above (3.4-6.8 kHz) the octave
      band noise exposure. For these f2 frequencies, DPOAE amplitudes decreased as
      exposure level increased up to approximately 72-80 dB SPL; higher exposure levels
      failed to cause any further reduction in DPOAE amplitude. The noise level at
      which DPOAE amplitude began to decrease was approximately 50 dB SPL. Above this
      critical level, DPOAE amplitude decreased 1.3 dB for every dB increase in noise
      level up to approximately 75 dB SPL.

PMID- 9925024
TI  - Influence of spontaneous otoacoustic emissions on distortion product otoacoustic
      emission amplitudes.
AB  - Although the influence of the levels and ratios of the primary stimulus on the
      amplitude of distortion product otoacoustic emissions (DPOAEs) has been studied
      intensely, the influence of the presence of spontaneous otoacoustic emissions
      (SOAEs) has been investigated less thoroughly. The present investigation analysed
      whether the unilateral presence of 58 SOAEs in 43 normal-hearing adults was
      related to larger DPOAEs in the ear with SOAEs compared to the contralateral ear
      having no SOAEs. The study was designed such that the only factor that could
      influence the amplitude of DPOAEs was the presence of SOAEs. Input/output (I/O)
      functions were collected in response to primary tones that were presented in 5-dB
      steps from 70 to 40 dB SPL at the frequency of the unilaterally recorded SOAE of
      each subject. The primary outcome was the demonstration of statistically
      significant (P < 0.05) larger DPOAEs in ears exhibiting SOAEs than in ears
      without measurable SOAEs, except at the highest stimulus level of 70 dB SPL.
      These results suggest that SOAEs play an additive role in the measurement of
      DPOAEs. The enhancing effect of the unilateral presence of SOAEs on DPOAEs was
      statistically significant for 65 dB SPL and lower levels of primary tones. The
      authors speculate that passive cochlear properties begin to participate in the
      generation of DPOAEs at primary-stimulus levels greater than 65 dB SPL.

PMID- 9925025
TI  - Antibody deposition in the stria vascularis of the MRL-Fas(lpr) mouse.
AB  - The MRL-Fas(lpr) mouse, a model of multisystemic, organ non-specific autoimmune
      disease, has been proposed as a model of immune-mediated inner ear disease.
      Preliminary studies indicate that it develops cochlear pathology focused in the
      stria vascularis including intracellular edema and degeneration which develops in
      the absence of an inflammatory infiltrate but in the presence of antibody
      deposition. It was thus hypothesized that the antibodies found in the stria were
      mediating a direct pathologic effect on this structure, without recruiting
      classical inflammatory mediators. It was further hypothesized that the antibodies
      deposited within the stria would be derived from the non-complement fixing
      isotypes and subclasses, which are known to be able to mediate direct pathologic
      effects on target tissues. This study utilized immunohistologic techniques to
      identify the antibody isotypes and subclasses deposited within the stria
      vascularis of the MRL-Fas(lpr) mouse. Results indicate that all antibody isotypes
      and subclasses can be identified within the stria vascularis in the absence of
      complement. Thus, antibody deposition was not restricted to non-complement fixing
      antibodies. While it is possible that antibodies are mediating direct pathologic
      effects within the stria, the non-specific nature of the antibody deposition may
      indicate that these antibodies are not responsible for the observed pathology.
      Rather, other mechanisms, such as metabolic and genetic etiologies, must also be
      considered.

PMID- 9925026
TI  - The existence region of Huggins' pitch.
AB  - Huggins' pitch (HP) can be heard when listening to white noise which is diotic at
      all frequencies except for a narrow band over which the interaural phase of the
      noise changes progressively through 360 degrees. The detectability (d') of HP was
      measured for 11 center frequencies between 100 Hz and 3200 Hz in half-octave
      steps. The listeners' task was to discriminate HP stimuli from diotic noises in a
      single-interval, YES/NO task. Detectability was simultaneously compared with that
      of pure tones presented interaurally out of phase and masked by diotic white
      noise (NoS pi). The levels of the tones were set so that they would fall below
      masked threshold monaurally at the higher frequencies tested. All four listeners
      showed similar patterns of detectability at high frequencies for both the Huggins
      pitch stimuli and the masked tones. The results showed that HP can be detected at
      higher frequencies than previously reported; all four listeners could detect both
      the tones and HP to some extent at 2256 Hz and one listener could also detect HP
      at 3200 Hz. The results demonstrate that both HP and NoS pi stimuli show a sharp
      drop in detectability at around 1500 Hz, but remain detectable at higher
      frequencies.

PMID- 9925027
TI  - cAMP mediates transepithelial K+ and Na+ transport in a strial marginal cell
      line.
AB  - Because cytoplasmic cAMP has been reported to be the secondary messenger
      mediating K+ transport in marginal cells of freshly isolated stria vascularis,
      the possible role of cAMP in ion transport processes of an immortalized marginal
      cell line (MCPV-8) showing evidence of K+ and Na+ reabsorption was evaluated in
      this study. Confluent MCPV-8 monolayers were mounted into Ussing chambers and
      perfused on both sides with perilymph-like Ringer's solution. Transepithelial
      short-circuit current (I(SC)), resistance (R(T)) and open-circuit voltage (V(T))
      were measured using voltage clamp technique. The following results were obtained.
      (1) Addition of forskolin (10(-4) M) to the basolateral perfusate increased I(SC)
      to 311 +/- 42%; no significant change in RT was observed. Addition of BaCl2 (2
      mM) to the apical perfusate at the maximal response of forskolin blocked 50-60%
      of I(SC) and subsequent addition of amiloride (10(-5) M) to the apical perfusate
      further blocked I(SC) to a value close to 0. (2) To evaluate the effect of
      cellular cAMP on Ba2+-sensitive K+ current, amiloride-sensitive Na+ current was
      blocked first by addition of amiloride (10(-5) M) to the apical perfusate;
      subsequent addition of 3-isobutyl-1-methylxanthine (IBMX, 1 mM) or N6,2'-O
      dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP, 1 mM) to the basolateral
      perfusate increased I(SC) to 175 +/- 13 and 411 +/- 32%, respectively. The
      stimulated I(SC) was blocked to close to 0 by addition of BaCl2 (2 mM) to the
      apical perfusate. N2,2'-O-Dibutyrylguanosine 3',5'-cyclic monophosphate (dbcGMP,
      1 mM) had no effect on I(SC). (3) To assess the effect of cellular cAMP on
      amiloride-sensitive Na+ current, Ba2+-sensitive K+ current was blocked in advance
      by addition of BaCl2 to the apical perfusate; subsequent addition of IBMX or
      dbcAMP to the basolateral perfusate increased I(SC) to 219 +/- 21% and 388 +/-
      39%, respectively. The stimulated I(SC) was blocked to close to 0 by addition of
      amiloride to the apical perfusate. dbcGMP had no effect on I(SC). Hence, these
      results suggest that cellular cAMP is the secondary messenger that mediates the
      transepithelial transport of both K+ and Na+ in MCPV-8 monolayers.

PMID- 9925028
TI  - On the factors required for obtaining protection against noise trauma by prior
      acoustic experience.

PMID- 9925029
TI  - Antioxidant status and dialysis: plasma and saliva antioxidant activity in
      patients with fluctuating urate levels.
AB  - The present study is concerned with the influence of processes occurring during
      dialysis on the antioxidant capacity of plasma and saliva. The biological fluids
      were also tested for uric acid and total protein content. Before hemodialysis,
      plasma antioxidant status of hemodialyzed patients appears slightly higher than
      the corresponding status in normal subjects; after hemodialysis it is found
      unchanged. The result can be explained by a balance between a reduction in uric
      acid plasma content, due to the dialytic procedure, and an increase in protein
      content, possibly due to a dialysis-related hemoconcentration. Moreover, pre
      dialysis total antioxidant capacity of whole saliva samples is higher than in
      healthy individuals and drastically decreases towards normal values following
      dialytic procedure. Our data indicate a certain concentration of the uric acid in
      the saliva of hemodialyzed patients and evidence that both total protein
      concentration and uric acid level show a good correlation with saliva total
      antioxidant capacity, suggesting that proteins are major antioxidants of this
      fluid. Further observations are needed to assess whether this improved saliva
      antioxidant ability has any consequence on the periodontal conditions of
      hemodialyzed subjects.

PMID- 9925030
TI  - Carvedilol inhibition of lipid peroxidation. A new antioxidative mechanism.
AB  - To define the molecular mechanism(s) of carvedilol inhibition of lipid
      peroxidation we have utilized model systems that allow us to study the different
      reactions involved in this complex process. Carvedilol inhibits the peroxidation
      of sonicated phosphatidylcholine liposomes triggered by FeCl2 addition whereas
      atenolol, pindolol and labetalol are ineffective. The inhibition proved not to be
      ascribable (a) to an effect on Fe2+ autoxidation and thus on the generation of
      oxygen derived radical initiators; (b) to the scavenging of the inorganic
      initiators O2*- and *OH; (c) to an effect on the reductive cleavage of organic
      hydroperoxides by FeCl2; (d) to the scavenging of organic initiators. The
      observations that (a) carvedilol effectiveness is inversely proportional to the
      concentration of FeCl2 and lipid hydroperoxides in the assay; (b) the drug
      prevents the onset of lipid peroxidation stimulated by FeCl3 addition and; (c) it
      can form a complex with Fe3+, suggest a molecular mechanism for carvedilol
      action. It may inhibit lipid peroxidation by binding the Fe3+ generated during
      the oxidation of Fe2+ by lipid hydroperoxides in the substrate. The lag time that
      carvedilol introduces in the peroxidative process would correspond to the time
      taken for carvedilol to be titrated by Fe3+; when the drug is consumed the Fe3+
      accumulates to reach the critical parameter that stimulates peroxidation.
      According to this molecular mechanism the antioxidant potency of carvedilol can
      be ascribed to its ability to bind a species, Fe3+, that is a catalyst of the
      process and to its lipophilic nature that concentrates it in the membranes where
      Fe3+ is generated by a site specific mechanism.

PMID- 9925032
TI  - Variability of oxygen radical absorbance capacity (ORAC) in different animal
      species.
AB  - The oxygen radical absorbance capacity (ORAC) was measured both in whole (ORAC-T)
      and deproteinized (ORAC-AS) plasma samples of human, pig, cow, rabbit, dog, cat,
      sheep, horse, dolphin, turkey, guinea-hen and chicken. In the 12 species, ORAC-T
      data, expressed as micromoles of peroxyl radicals trapped by 11 of sample, were
      found scattered between 8,600 and 23,000 micromol/l. The species with the highest
      ORAC-T values were cat among mammals and chicken among avies. ORAC-AS values
      ranged between 600 and 2000 micromol/l, with the highest values found in dolphin
      and sheep among mammals, while chicken was first among avies. In the 12 species,
      the relative contribution of ORAC-AS in relation to ORAC-T ranged from 5% to 20%.
      Protein SH-groups and uric acid were measured in plasma of all species, but no
      significant correlation was found between thiols and ORAC-T values or between
      uric acid and ORAC-AS values. Our results show that: (1) the ORAC method is
      reproducible and sensitive enough to be used in the comparison of the peroxyl
      radical absorbance capacity of protein and non-protein plasma components in
      different animal species; (2) both in mammals and in avies, there is a deep intra
      class heterogeneity of ORAC-T and ORAC-AS values; (3) by considering most
      species, plasma proteins and lipoproteins account for about 85-90% of the overall
      peroxyl-radical trapping capacity. In the dolphin only, the protein contribution
      decreases to 80%; (4) uric acid accounts for about one-half of the ORAC-AS value
      in human, guinea-hen and for about one-third in chicken, while it provides a very
      limited contribution in other species. We conclude that species with the highest
      ORAC-T, like cat and chicken, or with the highest ORAC-AS, like dolphin, are
      interesting models to study the reasons of such a marked antioxidant defense in
      the plasma.

PMID- 9925031
TI  - OxLDL-induced macrophage cytotoxicity is mediated by lysosomal rupture and
      modified by intralysosomal redox-active iron.
AB  - Oxidized low density lipoprotein (oxLDL) is believed to play a central role in
      atherogenesis. LDL is oxidized in the arterial intima by mechanisms that are
      still only partially understood. OxLDL is then taken up by macrophages through
      scavenger receptor-mediated endocytosis, which then leads to cellular damage,
      including apoptosis. The complex mechanisms by which oxLDL induces cell injury
      are mostly unknown. This study has demonstrated that oxLDL-induced damage of
      macrophages is associated with iron-mediated intralysosomal oxidative reactions,
      which cause partial lysosomal rupture and ensuing apoptosis. This series of
      events can be prevented by pre-exposing cells to the iron-chelator,
      desferrioxamine (DFO), whereas it is augmented by pretreating the cells with a
      low molecular weight iron complex. Since both DFO and the iron complex would be
      taken up by endocytosis, and thus directed to the lysosomal compartment, the
      results suggest that the normal contents of lysosomal low molecular weight iron
      may play an important role in oxLDL-induced cell damage, presumably by catalyzing
      intralysosomal fragmentation of lipid peroxides and the formation of toxic
      aldehydes and oxygen-centered radicals.

PMID- 9925033
TI  - Intra and intermolecular charge effects on the reaction of the superoxide radical
      anion with semi-oxidized tryptophan in peptides and N-acetyl tryptophan.
AB  - The reaction of the superoxide radical anion (O2-*), with the semi-oxidized
      tryptophan neutral radical (Trp*) generated from tryptophan (Trp) by pulse
      radiolysis has been observed in a variety of functionalized Trp derivatives
      including peptides. It is found that the reaction proceeds 4-5 times faster in
      positively charged peptides, such as Lys-Trp-Lys, Lys-Gly-Trp-Lys and Lys-Gly-Trp
      Lys-O-tert-butyl, than in solutions of the negatively charged N-acetyl tryptophan
      (NAT). However, the reactivity of O2-* with the Trp* radical is totally inhibited
      upon binding of these peptides to micelles of negatively charged SDS and is
      reduced upon binding to native DNA. By contrast, no change in reactivity is
      observed in a medium containing CTAB, where the peptides cannot bind to the
      positively charged micelles. On the other hand, the reactivity of the Trp*
      radical formed from NAT with O2-* is reduced to half that of the free Trp* in
      buffer but is markedly increased in CTAB micelles. The models studied here
      incorporate elements of the complex environment in which Trp* and O2-* may be
      concomitantly formed in biological system and demonstrate the magnitude of the
      influence such elements may have on the kinetics of reactions involving these two
      species.

PMID- 9925034
TI  - Short-term parenteral application of alpha-tocopherol leads to increased
      concentration in plasma and tissues of the rat.
AB  - Numerous studies suggest that supplemental vitamin E prior to or during vast
      surgeries might diminish or even prevent ischemia/reperfusion-induced injuries.
      In the present placebo-controlled study male Sprague-Dawley rats were
      supplemented parenterally or orally with alpha-tocopherol for three consecutive
      days. The applied amount of alpha-tocopherol was 2.3 micromol per day for oral
      and 1.2 micromol per day for parenteral supplementation. The enrichment of
      vitamin E concentrations in plasma and tissue samples (aortic endothelium, liver,
      and lung) was determined by HPLC. The vitamin E level was elevated following
      intravenous supplementation in plasma (21.4 +/- 1.9 micromol/L vs. 10.2 +/- 1.7
      micromol/L in parenteral control group), in aortic endothelium (1.1 +/- 0.2
      pmol/mm2 vs. 0.5 +/- 0.1 pmol/mm2) and in liver and lung (41.3 +/- 7.5 pmol/mg
      vs. 22.9 +/- 6.5 pmol/mg and 75.6 +/- 13.6 pmol/mg vs. 51.7 +/- 5.9 pmol/mg,
      respectively). Oral supplementation for three days also led to an increased level
      in liver (38.2 +/- 7.7 pmol/mg vs. 22.9 +/- 6.6 pmol/mg in oral control group)
      and in lung (67.8 +/- 5.7 pmol/mg vs. 51.7 +/- 9.3 pmol/mg) but not in aortic
      endothelium or plasma (0.8 +/- 0.3 pmol/mm2 vs. 0.6 +/- 0.3 pmol/mm2 and 12.0 +/-
      2.2 micromol/L vs. 10.7 +/- 2.6 micromol/L).

PMID- 9925035
TI  - Oxidative modification of human low-density lipoprotein by horseradish peroxidase
      in the absence of hydrogen peroxide.
AB  - Heme-peroxidases, such as horseradish peroxidase (HRP), are among the most
      popular catalysts of low density lipoprotein (LDL) peroxidation. In this model
      system, a suitable oxidant such as H2O2 is required to generate the hypervalent
      iron species able to initiate the peroxidative chain. However, we observed that
      traces of hydroperoxides present in a fresh solution of linoleic acid can promote
      lipid peroxidation and apo B oxidation, substituting H2O2. Spectral analysis of
      HRP showed that an hypervalent iron is generated in the presence of H2O2 and
      peroxidizing linoleic acid. Accordingly, careful reduction of the traces of
      linoleic acid lipid hydroperoxide prevented formation of the ferryl species in
      HRP and lipid peroxidation. However, when LDL was oxidized in the presence of
      HRP, the ferryl form of HRP was not detectable, suggesting a Fenton-like reaction
      as an alternative mechanism. This was supported by the observation that carbon
      monoxide, a ligand for the ferrous HRP, completely inhibited peroxidation of LDL.
      These results are in agreement with previous studies showing that myoglobin
      ferryl species is not produced in the presence of phospholipid hydroperoxides,
      and emphasize the relevance of a Fenton-like chemistry in peroxidation of LDL and
      indirectly, the role of pre-existing lipid hydroperoxides.

PMID- 9925036
TI  - Antioxidant properties of the decarboxylated dimer of aminoethylcysteine
      ketimine: assessment of its ability to scavenge peroxynitrite.
AB  - The natural sulfur compound aminoethylcysteine ketimine decarboxylated dimer
      (AECK dimer) has been investigated for its ability to act as peroxynitrite
      scavenger. It has been found that the product efficiently protects against the
      nitration of tyrosine and the inactivation of alpha1-antiproteinase by
      peroxynitrite. The tyrosine nitration can be completely prevented by 100 microM
      AECK dimer which appears as effective as the antioxidants glutathione and N
      acetylcysteine. The AECK dimer was also found to limit surface charge alteration
      of low density lipoprotein induced by peroxynitrite. These findings indicate that
      the AECK dimer is a strong protective agent against peroxynitrite damage and that
      it could play an important role in the defence against oxidative stress in human
      diseases.

PMID- 9925037
TI  - Electron spin resonance detection of extracellular superoxide anion released by
      cultured endothelial cells.
AB  - OBJECTIVE AND METHODS: Endothelium produces oxygen-derived free radicals which
      play a major role in vessel wall physiology and pathology. Whereas NO* production
      from endothelium has been extensively characterized, little is known about
      endothelium-derived O2-*. In the present study, we determined the O2-* production
      of bovine aortic endothelial cells (BAEC) using the spin trap 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) and electron spin resonance (ESR) spectroscopy. RESULTS:
      An ESR adduct DMPO-OH detected in the supernatant of BAEC after stimulation with
      the calcium ionophore A23187 originated from the trapping of extracellular O2-*,
      because coincubation with superoxide dismutase (30 U/ml) completely suppressed
      the ESR signal, whereas catalase (2000 U/ml) had no effect. A23187 stimulated
      extracellular O2-* production in a time- and dose-dependent manner. The coenzymes
      NADH and NADPH both increased the ESR signal, whereas a flavin antagonist,
      diphenylene iodonium, abolished the ESR signal. Phorbol myristate acetate
      potentiated, whereas bisindolylmaleimide I inhibited the A23187-stimulated O2-*
      production, suggesting the involvement of protein kinase C. These signals were
      not altered L-NAME, a NO-synthase inhibitor, suggesting that the endogenous
      production of NO* did not alter O2-* production. Finally, the amount of O2-*
      generated by A23187-stimulated post-confluent BAEC was one order of magnitude
      higher than that evoked by rat aortic smooth muscle cells stimulated under the
      same conditions.

PMID- 9925038
TI  - Inhibition of oxidant-induced lipid peroxidation in cultured renal tubular
      epithelial cells (LLC-PK1) by quercetin.
AB  - The protective effect of quercetin against oxidant-induced cell injury
      (hypoxanthine/xanthine oxidase system) was studied in the renal tubular
      epithelial cell line LLC-PK1. Pretreatment with quercetin provided protection
      from structural and functional cell damage in a concentration-dependent manner
      (10-100 microM). Comparison with structural variants revealed that the protective
      property of quercetin depends on the number of hydroxyl substituents in the B
      ring, the presence of an extended C-ring chromophore, 3-D-planarity and
      lipophilicity, indicating that membrane affinity is essential for protection. The
      hypothesis that quercetin exerts its protective effects via inhibition of lipid
      peroxidation was further examined. Protection by quercetin was found when lipid
      peroxidation, assessed by the release of malondialdehyde, was initiated by H2O2
      or by the combination of 1-chloro-2,4-dinitrobenzene and aminotriazole. In
      contrast, the bioflavonoid was not protective when oxidative cell damage was
      induced by menadione and occurred in the absence of lipid peroxidation. These
      data suggest that cytoprotective effects of quercetin are related to membrane
      affinity and may be explained by interruption of membrane lipid peroxidation
      rather than by intracellular scavenging of oxygen free radicals.

PMID- 9925039
TI  - Introduction to the featured section: genetic research on smoking.

PMID- 9925040
TI  - A genetic association for cigarette smoking behavior.
AB  - Dopaminergic genes are likely candidates for heritable influences on cigarette
      smoking. In an accompanying article, Lerman et al. (1999) report associations
      between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack
      of smoking, late initiation of smoking, and length of quitting attempts. The
      present investigation extended their study by examining both smoking behavior and
      personality traits in a diverse population of nonsmokers, current smokers, and
      former smokers (N = 1,107). A significant association between SLC6A3-9 and
      smoking status was confirmed and was due to an effect on cessation rather than
      initiation. The SLC6A3-9 polymorphism was also associated with low scores for
      novelty seeking, which was the most significant personality correlate of smoking
      cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism
      have altered dopamine transmission, which reduces their need for novelty and
      reward by external stimuli, including cigarettes.

PMID- 9925041
TI  - Evidence suggesting the role of specific genetic factors in cigarette smoking.
AB  - Twin studies suggest that propensity to smoke and ability to quit smoking are
      influenced by genetic factors. As a means of investigating the risk of smoking
      associated with genetic polymorphisms in the dopamine transporter (SLC6A3) and
      the D2 dopamine receptor (DRD2) genes, a case-control study of 289 smokers and
      233 nonsmoking controls and a case series analysis of smokers were conducted. A
      significant effect for SLC6A3 and a significant gene-gene interaction were found
      in a logistic regression model, indicating that individuals with SLC6A3-9
      genotypes were significantly less likely to be smokers, especially if they also
      had DRD2-A2 genotypes. Smokers with SLC6A3-9 genotypes were also significantly
      less likely to have started smoking before 16 years of age and had prior smoking
      histories indicating a longer period of prior smoking cessation. This study
      provides preliminary evidence that the SLC6A3 gene may influence smoking
      initiation and nicotine dependence.

PMID- 9925043
TI  - Eating orientation, postcessation weight gain, and continued abstinence among
      female smokers receiving an unsolicited smoking cessation intervention.
AB  - Predictors of weight gain following smoking cessation were assessed among 1,219
      female smokers enrolled in a health maintenance organization. Women randomized to
      the treatment group received a cessation intervention without regard to their
      interest in quitting smoking. It was hypothesized that cessation would result in
      subsequent weight gain and postcessation weight gain would be associated with
      scores on a modified Restraint Scale, the Disinhibition Scale, and a scale
      assessing tendency to eat during periods of negative affect. Persons who
      abstained from smoking over the 18-month study gained more weight than did
      intermittent smokers and continuous smokers, and among 762 women who reported at
      least 1 on-study attempt to quit smoking, 36% gained weight. Weight gain was
      associated with disinhibited eating and negative affect eating but not with
      restrained eating. Weight gain also was associated with continued abstinence from
      smoking.

PMID- 9925042
TI  - Interactive versus noninteractive interventions and dose-response relationships
      for stage-matched smoking cessation programs in a managed care setting.
AB  - This study compared interactive and noninteractive smoking cessation
      interventions for a population of smokers who were all members of 1 division of a
      managed care company. In addition, it examined whether a dose-response
      relationship existed. Screening was completed for 19,236 members who were
      contacted by telephone or mail. Of the 4,653 who were identified as smokers,
      85.3% were enrolled. A 2 Intervention (interactive or noninteractive) x 4
      Contacts (1, 2, 3, or 6 contacts) x 4 Occasions (0, 6, 12, and 18 months) design
      was used. The interactive intervention was stage-matched expert-system reports
      plus manuals; the noninteractive intervention was stage-matched manuals. Contact
      occurred in 1 of 4 series (1, 2, 3 or 6 contacts) at 3-month intervals. The
      expert system outperformed the stage-matched manuals, but there was no clear dose
      response relationship for either intervention.

PMID- 9925044
TI  - Underreporting sensitive behaviors: the case of young women's willingness to
      report abortion.
AB  - Accurate reports are important in health research, yet abortions are
      underreported in surveys by almost half. This study examined influences on
      reporting of abortion among adolescents. Participants were 63 young women from
      varied ethnic backgrounds who had undergone abortions at urban abortion clinics.
      Participants reported on their willingness to be honest about their abortion in
      various research settings and in comparison with other sensitive topics.
      Willingness to report was also examined in relation to the sponsor of the
      research, the mode of administration, and the characteristics of the interviewer.
      Adolescents indicated less willingness to report abortion than some behaviors
      such as cigarette smoking, but they were more willing to report abortion than
      family income, oral sex, or anal sex. Comparison of willingness to report across
      research settings indicated that face-to-face interviews appear to generate more
      accurate reporting than telephone surveys. The implications of these findings for
      the study of other health behaviors are discussed.

PMID- 9925045
TI  - Effects of hostility on ambulatory blood pressure and mood during daily living in
      healthy adults.
AB  - This study (a) tested the effects of hostile attributes on ambulatory blood
      pressure (BP), heart rate, and mood monitored repeatedly over 3 days in 100
      healthy men and women and (b) determined whether the cardiovascular effects of
      trait hostility were moderated by mood. Multilevel random-coefficients regression
      analyses showed that hostile individuals exhibited higher systolic and diastolic
      BP and rated their current moods as more negative and less positive throughout
      the monitoring. Individuals low in hostility exhibited high BP only during the
      few occasions when they experienced negative mood. However, these patterns were
      true only when participants were classified by Potential for Hostility ratings
      from the Structured Interview (R. H. Rosenman, 1978), not by the Cynical Hostile
      Attitudes score derived from the Cook-Medley scale. Results provide convergent
      and ecological validity of interview rating of hostility and illuminate one
      possible dynamic mechanism by which overt hostile behaviors might contribute to
      the rates of increased cardiovascular morbidity and mortality.

PMID- 9925046
TI  - Improving adjustment to chronic illness through strategic self-presentation: an
      experimental study on a renal dialysis unit.
AB  - Laboratory studies show that strategic self-presentations strongly influence
      private self-evaluations. The present study experimentally manipulated self
      presentations of dialysis patients' coping skills in order to influence their
      adjustment. In all, 42 renal dialysis patients matched for diabetes, gender, and
      dialysis years were randomly assigned to 3 conditions; adjustment was assessed at
      baseline, post-intervention, and 1 month follow-up. Patients in a self
      presentation condition selectively presented themselves as successful copers in a
      videotaped interview, ostensibly as part of a training program for new patients.
      Patients in a problem disclosure condition discussed problems with managing their
      illness. Control group patients viewed a medical videotape about adjusting to
      dialysis. Patients in the self-presentation condition reported better adjustment,
      fewer physical symptoms, and more coping skills 1 month later, compared with
      patients in the other 2 conditions. In addition, coping skills were shown to
      mediate the relationship between strategic self-presentation and adjustment.

PMID- 9925047
TI  - Social control in personal relationships: impact on health behaviors and
      psychological distress.
AB  - This study examines associations among social control, health behavior change,
      and psychological distress. Social control refers to interactions between social
      network members that entail regulation, influence, and constraint. Social control
      is predicted to have dual effects leading to better health practices while also
      arousing psychological distress. A random sample of 242 individuals answered
      questions about health practices, overall exposure to social control in their
      networks, and social control attempts made by a specific network member. Analyses
      yielded mixed support for the hypotheses, but analyses of responses to the social
      control attempts of a specific network member did reveal that social control
      predicted less health-compromising behavior and more health-enhancing behavior as
      well as more distress. The results suggest that social control warrants greater
      attention in efforts to understand how personal relationships influence health.

PMID- 9925048
TI  - A comparative test of the theory of reasoned action and the theory of planned
      behavior in the prediction of condom use intentions in a national sample of
      English young people.
AB  - Based on the theories of reasoned action (TRA) and planned behavior (TPB),
      predictors of condom use intentions were investigated in 949 young people (16-24
      years of age) from a national survey conducted in England. Contrary to
      expectations, the TPB did not perform significantly better than the TRA, even
      among women. Measures of past behavior were the best predictors of intentions and
      attenuated the effects of attitude and subjective norm. There was only weak
      evidence for the multiplicative assumption underlying the TRA and TPB. Although
      the TRA components were not the strongest predictors, the beliefs on which they
      are based are potentially amenable to change through information-based
      intervention programs. A number of practical suggestions for developing
      intervention strategies are offered.

PMID- 9925049
TI  - Occupational health psychology: historical roots and future directions.
AB  - Occupational health psychology (OHP) is a term first coined by Jonathan Raymond
      in 1990, yet OHP has historical, international roots dating at least to the early
      decades of the twentieth century. It involves research and practice to create
      healthy workplaces. This article has 4 sections. The 1st section discusses
      psychology's long history of concern for occupational health in industrial
      organizations, beginning with Hugo Munsterberg's study of industrial accidents
      and human safety in the late 1800s. The 2nd section focuses on OHP's movement
      from the convergence of public health and preventive medicine with health and
      clinical psychology in an industrial/organizational context. The 3rd section
      addresses the central issues of organizational and individual health through the
      framework of preventive management. The article concludes with OHP case examples
      drawn from the Chaparral Steel Company, the U.S. Air Force, and Johnson &
      Johnson.

PMID- 9925051
TI  - Complementary/alternative medicine for asthma: we do not know what we need to
      know.

PMID- 9925050
TI  - The theory of planned behavior and smoking cessation.
AB  - A sample of 84 smokers attending health promotion clinics in a primary care
      setting completed questionnaires that assessed the main constructs of the theory
      of planned behavior, perceived susceptibility, and past cessation attempts.
      Regression analyses revealed that intention to quit smoking was primarily
      predicted by perceived behavioral control and perceived susceptibility. At 6
      month follow-up, the making of a quit attempt was predicted by intention and the
      number of previous quit attempts, whereas the length of the quit attempt was
      predicted solely by the length of the longest recent quit attempt. The results
      suggest that interventions should focus on perceptions of susceptibility and
      control to increase smokers' motivation to quit. However, further work is
      required to identify the social cognitive variables that ensure that initial quit
      attempts are translated into longer term abstinence.

PMID- 9925052
TI  - Steroids in COPD: the nearly eternal question.

PMID- 9925053
TI  - Causes of chronic airway diseases.

PMID- 9925054
TI  - Full polysomnography in the home: has it come of age?

PMID- 9925055
TI  - Circulating natriuretic peptides: a biologic marker of tissue injury?

PMID- 9925056
TI  - Antimicrobial therapy of ventilator-associated pneumonia: how to select an
      appropriate drug regimen.

PMID- 9925057
TI  - Pharmacokinetics of rifampin under fasting conditions, with food, and with
      antacids.
AB  - STUDY OBJECTIVES: Determine the intrasubject and intersubject variability in, and
      the effects of food or antacids on, the pharmacokinetics of rifampin (RIF).
      DESIGN: Randomized, four-period crossover phase I study. SUBJECTS: Fourteen
      healthy male and female volunteers. INTERVENTIONS: Subjects ingested single doses
      of RIF, 600 mg, under fasting conditions twice, with a high-fat meal, and with
      aluminum-magnesium antacid. They also received standard doses of isoniazid,
      pyrazinamide, and ethambutol. MEASUREMENTS AND MAIN RESULTS: Serum was collected
      for 48 h and assayed by high-pressure liquid chromatography. Data were analyzed
      using noncompartmental methods and a compartmental analysis using nonparametric
      expectation maximization. Both fasting conditions produced similar results: a
      mean RIF maximal serum concentration (Cmax) of 10.54+/-3.18 microg/mL, the time
      at which it occurred (Tmax) of 2.42+/-1.32 h, and the area under the curve from
      time zero to infinity (AUC0-infinity) of 57.15+/-13.41 microg x h/mL. These
      findings are similar to those reported previously. Antacids did not alter these
      parameters (Cmax of 10.89+/-5.22 microg/mL, Tmax of 2.36+/-1.28 h, and AUC0
      infinity of 58.37+/-18.49 microg x h/mL). In contrast, the Food and Drug
      Administration high-fat meal reduced RIF Cmax by 36% (7.27+/-2.29 microg/mL),
      nearly doubled Tmax (4.43+/-1.09 h), but reduced AUC0-infinity by only 6%
      (55.20+/-14.48 microg x h/mL). CONCLUSIONS: These changes in Cmax, Tmax, and AUC0
      infinity can be avoided by giving RIF on an empty stomach whenever possible.

PMID- 9925058
TI  - The detection of airborne Mycobacterium tuberculosis using micropore membrane air
      sampling and polymerase chain reaction.
AB  - STUDY OBJECTIVES: Mycobacterium tuberculosis (MTb) bacilli are carried on
      airborne droplet nuclei produced by aerosolization that can occur from coughing,
      talking, or even singing. Because of their prolonged period of suspension, they
      can be filtered from the air onto a porous medium and readily detected using
      polymerase chain reaction (PCR). DESIGN: Prospective cohort analysis. SETTING:
      Samples of circulating air were collected over a 12-month period from within the
      rooms of 10 hospitalized patients who were under respiratory isolation to rule
      out MTb infection. A small laboratory pump was used to draw ambient air at a rate
      of 2 L/min over a 6-h period through a 0.2-microm polycarbonate membrane filter
      placed near the patient's bed. Analysis of the membrane filters was conducted
      using PCR. Sputum cultures for MTb were performed simultaneously, and the results
      of smears stained for acid-fast bacilli (AFB) were noted. MEASUREMENTS AND
      RESULTS: MTb complex was successfully detected by PCR in six of seven patients in
      whom sputum MTb cultures were subsequently positive, and in zero of three with
      subsequently negative sputum cultures. Sampling in one patient with a positive
      culture, in whom PCR results were negative, was only carried out for 2 h due to
      pump malfunction. One of the six PCR-positive patients was AFB-smear negative at
      the time of air sampling. CONCLUSIONS: Our preliminary findings indicate that the
      technique of Micropore membrane air sampling with PCR analysis has important
      applications in the epidemiology and diagnosis of MTb.

PMID- 9925059
TI  - Tuberculous pleural effusion in children.
AB  - STUDY OBJECTIVES: To describe the age distribution, clinical, laboratory,
      radiographic, and bacteriologic findings of pediatric patients with tuberculous
      pleural effusion. DESIGN: A retrospective study. PATIENTS AND METHODS: We have
      identified all cases of primary pulmonary tuberculosis in children < 18 years,
      reported to the health department. We have collected information from medical
      records regarding demographics, clinical findings, bacteriologic results, and
      evolution. Chest radiographs obtained at the time of initial evaluation were
      reviewed independently by two groups of radiologists who were blind to the
      clinical and epidemiologic data. RESULTS: Between January 1983 and December 1996,
      175 children < 18 years were diagnosed as having primary pulmonary tuberculosis.
      Among them, 39 patients (22.1%) showed pleural effusion on chest radiograph. The
      mean age of patients with tuberculous pleural effusion was significantly higher
      (13.52+/-0.5 years vs 6.97+/-0.42 years). The sensitivity of the tuberculin test
      is 97.4% for an induration > or = 5 mm. Pleural fluid analysis shows a
      lymphocytic exudative effusion. Chest radiograph review showed unilateral pleural
      effusion in all cases. Pleural effusion was the sole radiographic manifestation
      in 41% of cases. Parenchymal disease is associated in 23 cases (59%).
      Bacteriologic confirmation of tuberculosis was achieved in 22 cases (56.4%).
      Cultures of pleural fluid and biopsy material both yielded Mycobacterium
      tuberculosis in 15 of 34 (44.1%) and 12 of 18 (66.6%), respectively, for samples
      under study. Pleural biopsy specimens showed granulomatous inflammation in 18 of
      23 cases (78.3%). Antituberculous therapy for 6 to 9 months was effective in all
      cases. Transient side effects occurred in 1 of 39 patients (2.9%). CONCLUSIONS:
      Pleural effusion accounts for 22.1% of cases of pediatric pulmonary tuberculosis.
      Parenchymal consolidation is the most common associated radiographic finding.
      Bacteriologic confirmation was achieved in 56.4% of cases. A short course of
      chemotherapy is effective.

PMID- 9925060
TI  - The effect of high-dose inhaled beclomethasone dipropionate in patients with
      stable COPD.
AB  - BACKGROUND: The benefits of inhaled corticosteroids in the management of COPD are
      less apparent than they are in asthma therapy, and the potential for adverse
      systemic effects of high-dose inhaled corticosteroids has been recognized
      recently. It is therefore essential to know the maximal obtainable benefits in
      order to assess the risk/benefit ratio of this treatment. PURPOSE: The aim of
      this study was to investigate the maximal obtainable benefits of high-dose
      inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used
      in combination with adequate doses of regular bronchodilators in patients with
      stable COPD. STUDY DESIGN: Thirty patients with stable COPD completed a
      randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d
      of BDP or with a matching placebo using a metered-dose inhaler with a spacer
      device for 4 weeks during each treatment period. All of the patients continued to
      inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide
      qid. RESULTS: The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the
      placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP,
      five patients demonstrated a response in their FEV1 of more than 8.5% of the
      predicted value, which was above the range that covered 95% of the distribution
      of the placebo response. The mean absolute improvement in the FEV1 in these 5
      objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25
      objective nonresponders. Symptom scores for wheezing and dyspnea were
      significantly better with BDP than with placebo. Hoarseness and sore throat were
      associated more with BDP treatment. CONCLUSION: Although a considerable minority
      of patients benefited substantially from this treatment, the overall outcome does
      not seem to justify the widespread use of this treatment in the light of
      increasing recognition of the potential adverse systemic effects of high-dose
      inhaled corticosteroids.

PMID- 9925061
TI  - Theophylline for irreversible chronic airflow limitation: a randomized study
      comparing n of 1 trials to standard practice.
AB  - STUDY OBJECTIVE: To compare quality of life and exercise capacity (primary aim),
      and drug usage (secondary aim), between groups of patients with irreversible
      chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key
      Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard
      practice. DESIGN: Randomized study of n of 1 trials vs standard practice.
      SETTING: Outpatient departments in two tertiary care centers. PATIENTS: Sixty
      eight patients with irreversible CAL who were symptomatic despite the use of
      inhaled bronchodilators, and who were unsure whether theophylline was helping
      them following open treatment, were randomized into n of 1 trials (N=34) or
      standard practice. INTERVENTIONS: The n of 1 trials (single-patient, randomized,
      double-blind, multiple crossover comparisons of the effect on dyspnea of
      theophylline vs a placebo) followed published guidelines. Standard practice
      patients stopped taking theophylline but resumed it if their dyspnea worsened. If
      their dyspnea then improved, theophylline was continued. In both groups, a
      decision about continuing or stopping the use of theophylline was made within 3
      months of randomization. MEASUREMENTS AND RESULTS: The primary outcomes (the
      chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at
      baseline, 6 months, and 12 months by personnel blinded to treatment group
      allocation. No between-group differences (n of 1 minus standard practice) were
      seen in within-group changes over time (1 year minus baseline) in the CRQ
      Physical Function score (point estimate on the difference, -2.8; 95% confidence
      limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the
      difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the
      difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in
      the secondary outcome of the proportion of patients taking theophylline at 6 and
      12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during
      theophylline treatment compared with placebo treatment. CONCLUSIONS: Using n of 1
      trials to guide theophylline therapy in patients with irreversible CAL did not
      improve their quality of life or exercise capacity, or reduce drug usa e, over 1
      year compared to standard practice. Under the objective conditions of an n of 1
      trial, 21% of patients with CAL responded to theophylline. There remains a
      rationale for considering theophylline in patients with irreversible CAL who
      remain symptomatic despite the use of inhaled bronchodilators, but the use of n
      of 1 trials to guide this decision did not yield clinically important advantages
      over standard practice.

PMID- 9925062
TI  - Respiratory symptoms and pulmonary function in an elderly nonsmoking population.
AB  - OBJECTIVE: To examine risk factors for chronic airway disease (CAD) in elderly
      nonsmokers, as determined by pulmonary function tests (PFTs), and to correlate
      reported respiratory symptoms with PFT measures. DESIGN: An observational survey.
      SETTING: Several communities in California. MEASUREMENTS: Exposures and
      respiratory history were assessed by standardized questionnaire. PFTs were
      performed and prediction equations derived. RESULTS: Significant risk factors for
      obstruction on PFTs in multiple logistic regression included reported
      environmental tobacco smoke (ETS) exposure (relative risk [RR]=1.44), parental
      CAD or hay fever (RR=1.47), history of childhood respiratory illness (RR=2.15),
      increasing age, and male sex. The number of years of past smoking was of
      borderline significance (RR=1.29 for 10 years of smoking; p=0.06). The prevalence
      of obstruction on PFTs was 24.9% in those with definite symptomatic CAD, compared
      with 7.5% in those with no symptoms of CAD. The prevalence of obstruction was
      36.0% among those with asthma and 70.6% among those with emphysema. Also,
      symptomatic CAD correlated with reduction in lung function by analysis of
      covariance. The mean percent predicted FEV1 adjusted for covariates was 90.6% in
      persons with definite symptoms of CAD, compared with 97.8% in those without it (p
      < 0.001). CONCLUSIONS: Age, sex, parental history, childhood respiratory illness,
      and reported ETS exposures were significant risk factors for obstruction on PFTs.
      Self-reported respiratory symptoms also correlated significantly with PFTs.

PMID- 9925063
TI  - Discontinuous incremental threshold loading test: measure of respiratory muscle
      endurance in patients with COPD.
AB  - STUDY OBJECTIVE: To assess the discontinuous incremental threshold loading (DC
      ITL) test as a measure of respiratory muscle endurance for patients with COPD in
      terms of perceived breathing difficulty, reliability, and validity. DESIGN: The
      DC-ITL test was repeated three times at weekly intervals under identical test
      conditions. SETTING: Clinical research laboratory. PATIENTS: Forty-eight patients
      with moderate to severe COPD. MEASUREMENTS AND RESULTS: Rating of perceived
      breathing difficulty (RPBD) was measured at the end of each stage of the DC-ITL
      test with a Borg category-ratio scale. The maximal inspiratory pressure (PImax)
      was measured before and after the DC-ITL test. Breathing patterns were measured
      during the DC-ITL test. The mean (+/-SD) for RPBD at the maximal load was 6.3
      (3.1), 6.6 (2.8), and 6.7 (2.7) for visits one, two, and three, respectively (not
      significant). The mean relative maximal load for the DC-ITL test (peak mouth
      pressure as a percent of PImax) at the last completed stage was 59+/-23%, 62+/
      20%, and 63+/-19% for visits one, two, and three, respectively (not significant).
      Test-retest reliability was r1,2=0.82 and r2,3=0.69 for relative maximal load and
      r1,2=0.90 and r2,3=0.90 for absolute maximal load (peak mouth pressure). Tidal
      volume decreased (p < 0.01) and respiratory rate increased (p < 0.01) from the
      next-to-the-last to the last completed stage. PImax decreased after the DC-ITL
      test (p < 0.01). CONCLUSIONS: Moderate breathing difficulty was experienced
      during the DC-ITL test. The test was reliable and the results of this study
      support its validity as a measure of respiratory muscle endurance.

PMID- 9925064
TI  - Lung volumes in 4,774 patients with obstructive lung disease.
AB  - STUDY OBJECTIVES: To determine the correlates of static lung volumes in patients
      with airways obstruction, and to determine if static lung volumes differ between
      asthma and COPD. PATIENTS AND METHODS: We examined the data from all of the adult
      patients (mean age of 69) who were referred to a pulmonary function laboratory
      from January 1990 through July 1994 with an FEV1/FVC ratio of < 0.70 and tested
      using a body plethysmograph. Correlates were determined using regression
      analysis. MEASUREMENTS AND RESULTS: Of the 4,774 patients observed with evidence
      of airways obstruction, 61% were men. Self-reported diagnoses included asthma,
      19%; emphysema or COPD, 23%; chronic bronchitis, 1.5%; and alpha1-antiprotease
      deficiency, 0.6%. Fifty-six percent of the patients did not report a respiratory
      disease. The degree of hyperinflation, as determined by the residual volume
      (RV)/total lung capacity (TLC) ratio, or the RV % predicted (but not the TLC %
      predicted), was strongly associated with the degree of airways obstruction (the
      FEV1 % predicted). Patients with moderate to severe airways obstruction and high
      RV and TLC levels were more likely to have COPD than asthma. Of the 1,872
      patients with a reduced vital capacity determined by spirometry testing, 87% had
      hyperinflation as defined by the RV/TLC, and 9.5% had a low TLC (with less severe
      airways obstruction). CONCLUSION: In patients found to have airways obstruction
      by spirometry, the additional measurement of static lung volumes added little to
      the clinical interpretation.

PMID- 9925065
TI  - Improvements in lung function, exercise, and quality of life in hypercapnic COPD
      patients after lung volume reduction surgery.
AB  - STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on
      patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We
      prospectively examined morbidity, mortality, quality of life (QOL), and
      physiologic outcome, including spirometry, gas exchange, and exercise performance
      in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1),
      and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg
      (group 2). RESULTS: All preoperative physiologic and QOL indices were more
      impaired in the hypercapnic patients than in the eucapnic patients. The
      hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing
      capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction
      of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements.
      However, after surgery both groups exhibited improvements in FVC (group 1, p <
      0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung
      capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group
      1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p <
      0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1,
      p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1,
      p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02),
      and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001).
      However, because the magnitude of improvement was similar in both groups, and the
      hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk
      distance remained significantly lower post-LVRS in the hypercapnic patients.
      There was no difference in mortality between the groups (p=0.9). CONCLUSIONS:
      Patients with moderate to severe resting hypercapnia exhibit significant
      improvements in spirometry, gas exchange, perceived QOL, and exercise performance
      after bilateral LVRS. The maximal achievable improvements in postoperative lung
      function are related to preoperative level of function; however, the magnitude of
      improvement can be expected to be similar to patients with lower resting PaCO2
      levels. Patients should not be excluded from LVRS based solely on the presence of
      resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains
      to be determined.

PMID- 9925066
TI  - Lack of correlation of symptoms with specialist-assessed long-term asthma
      severity.
AB  - STUDY OBJECTIVES: To validate three indicators of asthma severity as defined in
      the National Asthma Education Program (NAEP) guidelines (ie, frequency of
      symptoms, degree of airflow obstruction, and frequency of use of oral
      glucocorticoids), alone and in combination, against severity as assessed by
      pulmonary specialists provided with 24-month medical chart data. DESIGN: Cross
      sectional comparison of questionnaire and clinical-based markers of asthma
      severity with physician-assessed severity based on chart review. The
      pulmonologists did not have access to the results of the baseline evaluations
      when making their severity assessments. SETTING AND PARTICIPANTS: Study
      participants were 193 asthmatic members (age range, 6 to 55 years) of a large
      health maintenance organization who underwent a baseline evaluation as part of a
      separate longitudinal study. This evaluation consisted of spirometry, skin prick
      testing, and a survey that included questions on symptoms and medication use. The
      participants in the ancillary study were selected, based on their baseline
      evaluation, to reflect a broad range of asthma severity. RESULTS: Based on the
      chart review, 86 of the study subjects (45%) had mild disease, 90 (45%) had
      moderate disease, and 17 (9%) had severe disease. This physician-assessed
      severity correlated highly (p < or = 0.013) with NAEP-based indices of severity
      based on oral glucocorticoid use (never, infrequently for attacks, frequently for
      attacks, and daily use) and on spirometry (FEV1 > 80% predicted, 60 to 80%
      predicted, and <60% predicted). It did not, however, correlate with current
      asthma symptoms (< or = once/week, 2 to 6 times/week, daily) (p=0.87). A
      composite severity score based on spirometry and the glucocorticoid use data
      still provided an overall agreement of 63%, with a weighted kappa of 0.40.
      CONCLUSIONS: While current symptoms are the most important concern of patients
      with asthma, they reflect the current level of asthma control more than
      underlying disease severity. Investigators must therefore use caution when
      comparing groups of patients for whom severity categorization is based largely on
      symptomatology. This observation, that symptoms alone do not reflect disease
      severity, becomes even more important as health-care delivery moves closer to
      protocols/practice guidelines and "best treatment" programs that rely heavily on
      symptoms to guide subsequent treatment decisions.

PMID- 9925067
TI  - Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute
      asthma.
AB  - PURPOSE: The optimal dose of albuterol to use in the treatment of acute asthma
      has yet to be established. The National Asthma Education and Prevention Program
      (NAEPP) recommends a starting dose of 2.5 to 5 mg of aerosolized albuterol every
      20 min, although European authorities recommend higher doses. The purpose of this
      study was to compare 2.5 vs 7.5 mg of nebulized albuterol for the treatment of
      acute asthma. SUBJECTS: We studied 160 patients presenting to the emergency
      department with acute asthma. METHODS: On enrollment, patients underwent baseline
      testing, including initial spirometry. All patients received prednisone, 60 mg,
      orally. Patients then received in a randomized, double-blinded fashion, nebulized
      albuterol either 2.5 or 7.5 mg every 20 min for a total of three doses.
      Spirometry was repeated after each of the first two treatments and again 40 min
      after completion of the three treatments. RESULTS: The pretreatment FEV1 was
      36.9+/-16.6% of predicted normal in the low-dose group vs 41.5+/-15.4% of
      predicted normal in the high-dose group (not significant [NS]). The patients in
      the low-dose group had a 50.3+/-62.6% improvement in FEV1 pretreatment to post
      treatment, whereas those in the high-dose group had a 44.6+/-48.2% improvement in
      FEV1 (NS). There was no difference in the admission rate in the low-dose group
      (43%) as compared with that of the high-dose group (39%; NS). CONCLUSION: We
      conclude that there is no advantage to the routine administration of doses of
      albuterol higher than 2.5 mg every 20 min. It is possible that there may be an
      advantage in the most severely obstructed patients, although this study did not
      enroll enough patients with very severe asthma to evaluate this. As has been
      previously demonstrated, patients who subsequently require admission have a
      diminished response to albuterol. This decreased responsiveness is seen with the
      first aerosol administration and is unaffected by increasing the dose.

PMID- 9925068
TI  - Variable extrathoracic airflow obstruction and chronic laryngotracheitis in Gulf
      War veterans.
AB  - STUDY OBJECTIVES: To study the flow-volume loop for evidence of variable
      extrathoracic airflow obstruction in Persian Gulf War veterans. DESIGN:
      Retrospective case-control, single-center study. SETTING: The pulmonary division
      of an academic health-care center. SUBJECTS: A convenience sample of the Persian
      Gulf Registry. MEASUREMENTS AND INTERVENTIONS: (1) Midvital capacity ratio (ratio
      of maximum forced midexpiratory to maximum forced midinspiratory flow). This
      ratio is the criterion standard for the diagnosis of variable extrathoracic
      airflow obstruction. (2) Evaluation of the anatomy and function of the
      extrathoracic airway by fiberoptic bronchoscopy. (3) Further investigation into
      the airway abnormality by histologic evaluation of tracheal biopsy samples in
      Gulf War veterans only. RESULTS: Midvital capacity was > 1.0 in 32 of 37 Gulf War
      veterans compared with only 11 of 38 control subjects. The mean (+/-SD) value was
      1.37+/-0.4 among Gulf War veterans and 0.88+/-0.3 among control subjects
      (p=0.0000005). FVC and its ratio to FEV1 were normal in all these subjects.
      Bronchoscopy showed inflamed larynx and trachea in all (n=17) Gulf War veterans.
      Histologic study showed chronic inflammation of the trachea in everyone (n=12)
      who had an adequate biopsy sample. CONCLUSION: Physicians should be made aware of
      the presence of chronic inflammation of the upper airways and inspiratory airflow
      limitation in a number of Gulf War veterans.

PMID- 9925069
TI  - Effects of sodium bicarbonate administration on the exercise tolerance of normal
      subjects breathing through dead space.
AB  - STUDY OBJECTIVE: The purpose of this study was to determine whether the
      administration of sodium bicarbonate to normal individuals would increase their
      PaCO2 and thereby decrease the ventilatory requirements at a given workload.
      DESIGN: In this double-blind crossover study, six normal men ingested either 3
      mEq/kg NaHCO3 or 1 mEq/kg NaCl once a day for 5 days, in addition to 40 mg of
      furosemide and 40 mEq KCl. After each 5-day treatment, the subjects underwent a
      symptom-limited maximal bicycle ergometer exercise test while breathing through
      external dead space (with a volume of approximately 50% of their FEV1), a second
      exercise test without any external dead space, and an assessment of their
      respiratory response to hypercapnia. RESULTS: The administration of the NaHCO3
      resulted in a significant increase in the arterial HCO3- from 20.8 to 24.0 mEq/L
      and a significant increase in the PaCO2 from 31.7 to 36.9 mm Hg at rest that
      persisted during exercise. During exercise periods with the added dead space, the
      Borg scores were significantly lower at each workload after the subjects received
      bicarbonate, but the maximal exercise level did not increase. The mean (+/-SD)
      slope of the mouth occlusion pressure response to hypercapnia was significantly
      lower after the administration of NaHCO3 than after NaCl, respectively: 0.73+/
      0.41 vs 1.27+/-0.97 cm H2O/mm Hg. CONCLUSION: From this study we conclude that
      the administration of NaHCO3 results in a significant increase in the PaCO2,
      decreases the ventilation and the Borg score at equivalent workloads, and
      decreases the hypercapnic response in normal individuals.

PMID- 9925070
TI  - Sensitivity and specificity of radioisotope right-left shunt measurements and
      pulse oximetry for the early detection of pulmonary arteriovenous malformations.
AB  - STUDY OBJECTIVES: To assess the effectiveness of pulse oximetry and radioisotope
      measurement of right-to-left (R-L) shunt for the early detection of pulmonary
      arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic
      telangiectasia (HHT). DESIGN: Patients with HHT had serial measurements of the
      following: (1) arterial oxygen saturation (SaO2) by pulse oximetry in erect and
      supine positions, and on maximal exercise using cycle ergometry; (2) quantitative
      radioisotope measurements of R-L shunt using IV 99mTc-labeled macroaggregates of
      albumin; and (3) routine pulmonary function. After percutaneous transcatheter
      embolization of all PAVMs with feeding vessel diameters > 3 mm, residual PAVMs
      were assessed with selective digital subtraction pulmonary angiography. Using
      postembolization angiography as the "gold standard," SaO2 and radioisotope shunt
      measurements after embolization were analyzed retrospectively using logistic
      regression to assess the ability of each test to predict for the presence of
      residual PAVMs. RESULTS: Of the 66 patients included, 40 had small PAVMs
      remaining postembolization. Using univariate logistic regression, radioisotope
      shunt and erect saturation showed a significant relationship with the presence of
      residual PAVMs (p=0.001, 0.005, respectively). Erect SaO2 < or = 96% had 73%
      sensitivity and 35% specificity for detecting PAVMs. Radioisotope shunt >3.5% of
      cardiac output had 87% sensitivity and 61% specificity for detecting PAVMs.
      CONCLUSIONS: These results confirm that noninvasive measurements are useful in
      the screening of patients with HHT for the presence of PAVMs without need for
      angiography and its associated risks, and that radionuclide scanning is better
      than pulse oximetry.

PMID- 9925071
TI  - Portable computerized polysomnography in attended and unattended settings.
AB  - STUDY OBJECTIVE: We compared the validity of a new portable polysomnographic
      recorder against a laboratory-based polysomnographic system from the same
      manufacturer. DESIGN AND PATIENTS: Simultaneous, full polysomnographic recordings
      from the portable device (PSGP) and the laboratory-based system (PSGL) were
      obtained using separate sets of sensors on 20 patients referred for investigation
      of sleep apnea. SETTING: After initial optimization of signals, the portable
      device was left unattended in 10 of the patients (to simulate home studies),
      while in the other 10 the signals were reviewed on a laptop computer screen and
      adjustments to electrode or sensor placement made as needed during the studies.
      Recordings were manually scored by a technologist blinded to the origin of the
      data. MEASUREMENTS AND RESULTS: The quality of signals was comparable between the
      PSGP and PSGL studies, apart from a slight decrease in respiratory signal quality
      during PSGP studies that led to reduced confidence in respiratory event scoring.
      SaO2 signal loss was also greater in unattended PSGP. There was good agreement
      between PSGP and PSGL for sleep variables and the apnea-hypopnea index (r=0.99).
      The periodic limb movement index was slightly lower during unattended PSGP.
      Blinded physician assessment of the records led to a recommendation for repeat
      studies due to poor signal quality in one (10%) attended and one (10%) unattended
      portable recording. There was no significant discordance between PSGP and PSGL in
      the final diagnostic formulations. CONCLUSION: Portable polysomnography is a
      viable alternative to laboratory-based polysomnography and may be improved
      further by better sensor attachment.

PMID- 9925072
TI  - Quality of life in patients with obstructive sleep apnea: effect of nasal
      continuous positive airway pressure--a prospective study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common condition and is associated
      with excessive daytime sleepiness and neuropsychological dysfunction. There is
      limited evidence on the effect of OSA on the quality of life and its response to
      nasal continuous positive airway pressure (nCPAP) treatment. STUDY OBJECTIVE: To
      determine the effect of nCPAP on the quality of life in patients with OSA.
      DESIGN: Prospective determination of nCPAP effect in a case-series analysis.
      PATIENTS: We studied 29 patients (23 were male and 6 were female) with a mean (+/
      SE) age of 4.4+/-2.3 years, a body mass index 36.3+/-2.0 kg/height (m)2, and a
      diagnosis of OSA with respiratory disturbance index (RDI; apnea/hypopnea) of 77+/
      9 events/h. MEASUREMENTS AND RESULTS: The quality of life was assessed by
      administering a Medical Outcomes Study Short Form-36 questionnaire before and
      after 8 weeks of nCPAP therapy in polysomnographically documented OSA. All
      dimensions of the quality of life were significantly impaired when compared with
      an age- and gender-matched population, expressed as a percentage of normative
      data: physical functioning, 75%; vitality, 41%; role functioning (physical, 54%;
      emotional, 61%; social, 66%); general health, 88%; and mental health, 76%. nCPAP
      therapy significantly improved the sleep-disordered breathing and sleep
      fragmentation. The nCPAP level for the group was 9.4+/-0.7 cm H2O. Eight weeks of
      nCPAP therapy improved vitality (75%), social functioning (90%), and mental
      health (96%). The magnitude of improvement was related to the degree of quality
      of life impairment prior to treatment, rather than to the severity of disease as
      measured by the RDI and arousal indices. CONCLUSIONS: All aspects of the quality
      of life, from physical and emotional health to social functioning, are markedly
      impaired by OSA. nCPAP therapy improved those aspects related to vitality, social
      functioning, and mental health.

PMID- 9925073
TI  - Elevated plasma atrial natriuretic peptide levels after occlusion of the thoracic
      aorta.
AB  - STUDY OBJECTIVE: The influence of occlusion of the thoracic aorta by an
      intraluminal balloon on plasma atrial natriuretic peptide (ANP) levels was
      evaluated in humans. METHODS: The changes in plasma ANP and plasma norepinephrine
      levels, and hemodynamic parameters were measured in 10 patients under general
      anesthesia undergoing regional chemotherapy treatment involving the 15-min
      inflation and subsequent deflation of an intraaortic balloon. RESULTS: The
      hemodynamic changes observed were similar to those seen during aortic clamping
      and declamping in patients undergoing vascular surgery. Plasma ANP levels
      (median+/-SD) measured 1 min after inflation (146+/-117 pg/mL) and 1 min after
      deflation (168+/-189 pg/mL) of the aortic balloon were significantly higher than
      baseline values (83+/-55 pg/mL), with a mean increase, respectively, of 92% and
      97% (95% confidence intervals [CI], 50 to 147% and 53 to 152%). Plasma ANP levels
      were still elevated 30 min after deflation (121+/-94 pg/mL), a 56% increase (95%
      CI, 21 to 100%), although the hemodynamic parameters had already returned to
      their baseline levels. There was no evidence that the hemodynamic variables were
      associated with changes in plasma ANP levels (all p values > 0.30). In addition,
      there was no evidence of an association between plasma ANP and plasma
      norepinephrine levels at any of the four individual sampling points (p > 0.17).
      Thirty minutes after deflation, however, norepinephrine levels were higher than
      baseline values. CONCLUSIONS: The changes in plasma ANP levels after aortic
      occlusion and reinstitution of blood flow may be dependent on parameters other
      than atrial stretch and pressure.

PMID- 9925074
TI  - Can retrograde cardioplegia alone provide adequate protection for cardiac valve
      surgery?
AB  - BACKGROUND: When aortic insufficiency is present, antegrade delivery of
      cardioplegia requires coronary cannulation. Use of retrograde cardioplegia
      simplifies administration. The efficacy of the retrograde route alone in ensuring
      adequate myocardial protection may be assessed by the clinical outcome. METHODS
      AND RESULTS: We used closed transatrial coronary sinus perfusion as the sole
      method of cardioplegia delivery in 100 patients who underwent valve operations,
      either isolated or combined with coronary (n=24), ascending aortic aneurysm
      (n=8), or other procedures. Eighty-one patients were in New York Heart
      Association (NYHA) Class III or IV; 23 had undergone previous heart operations;
      23 were admitted from the coronary care unit (CCU); and 20 had left ventricular
      ejection fraction (LVEF) of < or = 40%. Operative mortality was 2%. An intra
      aortic balloon pump was required in eight patients. On univariate analysis,
      perioperative use of inotropes (n=26) was related to age > or = 70 years
      (p=0.02), COPD (p=0.05), pulmonary hypertension (p=0.005), higher NYHA Class
      (p=0.0006), preoperative heart failure (p=0.006), lower LVEF (p=0.0003), urgency
      (p=0.00001), admission from the CCU (p=0.006), repeat operation (p=0.03),
      coronary artery disease (p=0.02), and longer ischemic (p=0.02) and bypass times
      (p=0.0003). On multivariate stepwise logistic regression analysis, use of
      inotropes was related to preoperative lower LVEF (p=0.02) and urgency of
      operation (p=0.0002). Perioperative complications included ventricular arrhythmia
      in six, heart block in one, renal dysfunction in nine, and stroke in two
      patients; no patient had myocardial infarction. CONCLUSION: Good clinical results
      can be obtained by using retrograde cardioplegia alone without prior doses of
      antegrade cardioplegia in all valve operations.

PMID- 9925075
TI  - Atrial thrombi resolution after prolonged anticoagulation in patients with atrial
      fibrillation.
AB  - BACKGROUND: Cardioversion of atrial fibrillation in nonanticoagulated patients
      may be associated with clinical thromboembolism. Prolonged anticoagulation with
      warfarin before cardioversion of atrial fibrillation produces a marked reduction
      of cardioversion-related thromboembolism. The benefit of anticoagulant therapy is
      generally believed to be due to atrial thrombi organization. PATIENTS AND
      METHODS: Transesophageal echocardiography (TEE) is highly accurate for diagnosis
      of atrial thrombi and gives the possibility to serially evaluate the effects of
      anticoagulant therapy. One hundred twenty-three patients with atrial fibrillation
      lasting longer than 2 days underwent TEE before cardioversion. An atrial thrombus
      was identified in 11 patients (9%), and was always confined to the left atrial
      appendage. TEE was repeated after a median of 4 weeks of oral warfarin. Atrial
      thrombus had completely resolved in 9 of 11 patients (81.8%; 95% CI, 48.2 to
      97.7%); in two patients, clot was still present. No patient had clinical
      thromboembolism between the two TEE studies. CONCLUSIONS: In the population of
      our study, a prolonged course of warfarin therapy was associated with resolution
      of atrial thrombi in the majority of patients. According to these data, the
      mechanism of thromboembolism reduction with 4 weeks of anticoagulation before
      cardioversion in patients with atrial fibrillation seems to be related mainly to
      thrombus lysis rather than organization. Due to the possibility of thrombus
      persistence even after prolonged anticoagulation, follow-up with TEE before
      cardioversion is necessary to document thrombus resolution.

PMID- 9925076
TI  - Neoadjuvant etoposide, ifosfamide, and cisplatin followed by concomitant thoracic
      radiotherapy and continuous cisplatin infusion in stage IIIb non-small cell lung
      cancer.
AB  - OBJECTIVE: To determine the applicability and safety of an ifosfamide, cisplatin,
      and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant
      thoracic radiotherapy and cisplatin continuous infusion in locally advanced non
      small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients (stage
      IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant
      thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted
      of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection),
      and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic
      support using recombinant human methionyl granulocyte colony stimulating factor.
      Patients who achieved a response or a stabilization were planned to receive a
      split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4
      week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6
      mg/m2 daily was administered using an autonomous chemotherapy delivery device.
      Total plasma platinum titration was performed daily during the two courses in
      five of the patients. Analyses were done on an intent-to-treat basis. RESULTS:
      Thirty-nine of the 44 patients received the three-cycle chemotherapy program.
      Received dose intensity was 82%. Thirty-eight patients received the radiotherapy
      and, among them, 35 received the complete concomitant continuous cisplatin
      infusion. Objective (complete) response rates were 48% (7%) at the end of
      chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end
      of the first radiotherapy cycle, the mean total plasma platinum concentration was
      twice as high as that of the residual postinduction chemotherapy concentration.
      During induction chemotherapy, myelosuppression was the limiting toxicity
      requiring hospital readmission in 23 patients. During radiotherapy, the main
      toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was
      observed using the subjective objective management analytic--late effects of
      normal tissue score without life-threatening pulmonary function impairment. None
      of the patients died from toxic reactions. Probability of survival at 1, 2, and 3
      years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local
      relapse in 63% of the patients, brain metastases in 24%, and hematogeneous
      metastases to other sites in 13%. CONCLUSION: Neoadjuvant VIP followed by
      concomitant radiotherapy-chemotherapy is feasible, but the split-course
      radiotherapy did not prevent a high rate of local recurrences. The high rate of
      toxic reactions requiring hospital readmission limits further development of such
      an aggressive regimen in NSCLC.

PMID- 9925077
TI  - Intrapulmonary cytokine accumulation following BAL and the role of endotoxin
      contamination.
AB  - STUDY OBJECTIVES: BAL induces alveolar inflammation, but its effects on
      intrapulmonary cytokines and the mechanisms causing inflammation are uncertain.
      The objectives of this study were: (1) to characterize cytokine response in the
      lungs to BAL, and (2) to determine whether endotoxin is introduced into the lungs
      during BAL, which could promote BAL-induced inflammation. DESIGN AND METHODS: We
      performed two BAL procedures in healthy volunteers separated by 4 (n=6), 24
      (n=5), or 72 h (n=3). The initial BAL was performed in the right middle lobe
      (RML) and the second BAL was performed in the same location and the lingula.
      Concentrations of interleukin-8 (IL-8), interleukin-1 (IL-1beta), and
      transforming growth factor-beta were measured by enzyme-linked immunosorbent
      assay and tumor necrosis factor-alpha (TNF-alpha) bioactivity was determined.
      Endotoxin contents of saline (10 and 20 mL) infused through bronchoscopes as well
      as BAL fluids recovered from six subjects were assessed by limulus amebocyte
      assay. RESULTS: At 4 h after the initial lavage, but not at later times, BAL
      fluid recovered from the RML contained increased concentrations of IL-8 and IL
      1beta, and increased TNF-alpha bioactivity. BAL fluid recovered from the lingula
      contained increased concentrations of TNF-alpha only at 4 h. All BAL samples
      tested contained detectable endotoxin as did all saline aliquots instilled
      through bronchoscopes. CONCLUSIONS: There is intrapulmonary accumulation of the
      cytokines TNF-alpha, IL-8, and IL-1beta in the lavaged lung within 4 h after BAL;
      this accumulation resolves by 24 h. Endotoxin contamination of the lungs during
      bronchoscopy may contribute to BAL-induced lung inflammation.

PMID- 9925078
TI  - The importance of physical fitness in the performance of adequate cardiopulmonary
      resuscitation.
AB  - The aim of the present investigation was to evaluate the influence of the
      physical fitness of a cardiopulmonary resuscitation (CPR) provider on the
      performance of and physiologic response to CPR. To this end, comparisons were
      made of sedentary and physically active subjects in terms of CPR performance and
      physiologic variables. Two study groups were established: group P (n=14),
      composed of sedentary, professional CPR rescuers (mean [+/-SD]; age, 34+/-6
      years; VO2max, 32.5+/-5.5 mL/kg/min), and group Ex (n=14), composed of physically
      active, nonexperienced subjects (age, 34+/-6 years; VO2max, 44.5+/-8.5
      mL/kg/min). Each subject was required to perform an 18-min CPR session, which
      involved manual external cardiac compressions (ECCs) on an electronic teaching
      mannequin following accepted standard CPR guidelines. Subjects' gas exchange
      parameters and heart rates (HRs) were monitored throughout the trial. Variables
      indicating the adequacy of the ECCs (ECC depth and the percentage of incorrect
      compressions and hand placements) also were determined. Overall CPR performance
      was similar in both groups. The indicators of ECC adequacy fell within accepted
      limits (ie, an ECC depth between 38 and 51 mm). However, fatigue prevented four
      subjects from group P from completing the trial. In contrast, the physiologic
      responses to CPR differed between groups. The indicators of the intensity of
      effort during the trial, such as HR or percentage of maximum oxygen uptake
      (VO2max) were higher in group P subjects than group Ex subjects, respectively
      (HRs at the end of the trial, 139+/-22 vs 115+/-17 beats/min, p < 0.01;
      percentage of VO2max after 12 min of CPR, 46.7+/-9.7% vs 37.2+/-10.4%, p < 0.05).
      These results suggest that a certain level of physical fitness may be beneficial
      to CPR providers to ensure the adequacy of chest compressions performed during
      relatively long periods of cardiac arrest.

PMID- 9925079
TI  - Blast lung injury from an explosion on a civilian bus.
AB  - OBJECTIVE: To assess clinical signs and management of primary blast lung injury
      (BLI) from explosions in an enclosed space and to propose a BLI severity scoring
      system. DESIGN: Retrospective analysis. PATIENTS: Fifteen patients with primary
      BLI resulting from explosions on two civilian buses in 1996. RESULTS: Ten
      patients were extremely hypoxemic on admission (PaO2 < 65 mm Hg with oxygen
      supplementation). Four patients remained severely hypoxemic (PaO2/fraction of
      inspired oxygen (FIO2) ratio of < 60 mm Hg) after mechanical ventilation was
      established and pneumothoraces were drained. Initial chest radiographs revealed
      bilateral lung opacities of various sizes in 12 patients (80%). Seven patients
      (47%) had bilateral pneumothoraces and two patients had a unilateral
      pneumothorax. Five (33%) had clinically significant bronchopleural fistulae.
      After clinical and laboratory data were collected, a BLI severity score was
      defined based on hypoxemia (PaO2/FIO2 ratio), chest radiographic abnormalities,
      and barotrauma. Severe BLI was defined as a PaO2/FIO2 ratio of < 60 mm Hg,
      bilateral lung infiltrates, and bronchopleural fistula; moderate BLI as a
      PaO2/FIO2 ratio of 60 to 200 mm Hg and diffuse (bilateral/unilateral) lung
      infiltrates with or without pneumothorax; and mild BLI as a PaO2/FIO2 ratio of >
      200, localized lung infiltrates, and no pneumothorax. Five patients developed
      ARDS with Murray scores > 2.5. Respiratory management included positive pressure
      ventilation in the majority of the patients and unconventional methods (ie, high
      frequency jet ventilation, independent lung ventilation, nitric oxide, and
      extracorporeal membrane oxygenation) in patients with severe BLI. Of the four
      patients who had severe BLI, three died. All six patients with moderate BLI
      survived, and four of five with mild BLI survived (one with head injury died).
      CONCLUSIONS: BLI can cause severe hypoxemia, which can be improved significantly
      with aggressive treatment. The lung damage may be accurately estimated in the
      early hours after injury. The BLI severity score may be helpful in determining
      patient management and prediction of final outcome.

PMID- 9925080
TI  - Noninvasive positive pressure ventilation: successful outcome in patients with
      acute lung injury/ARDS.
AB  - BACKGROUND: There is increasing support for the use of noninvasive positive
      pressure ventilation (NPPV) in the treatment of patients with acute respiratory
      failure. Highest success rates are recorded in patients with exacerbation of
      COPD, particularly in patients presenting primarily with hypercarbic respiratory
      failure. Success has been more limited in patients with acute hypoxemic
      respiratory failure, and there are few reports of NPPV in patients with acute
      lung injury (ALI) or ARDS. OBJECTIVES: We report the outcome of 12 episodes of
      ALI/ARDS in 10 patients treated with NPPV. DESIGN: Experiential cohort study.
      SETTING: Tertiary referral center and university hospital ICU. INTERVENTION:
      Provision of NPPV in patients with ALI/ARDS. RESULTS: Group median (range) APACHE
      (acute physiology and chronic health evaluation) II score was 16 (11 to 29).
      Success rate (avoidance of intubation and no further assisted ventilation for 72
      h) was achieved on six of nine occasions (66%) when NPPV was used as the initial
      mode of assisted ventilation. It failed after three episodes of planned (1) or
      self (2) extubation. Duration of successful NPPV was 64.5 h (23.5 to 80.5 h) with
      ICU discharge in the next 24 to 48 h for three of six patients. Unsuccessful
      episodes lasted 7.3 h (0.1 to 116 h) with need for conventional ventilation for
      an additional 5 days (2.7 to 14 days). Survival (ICU and hospital) for the 10
      patients was 70%. CONCLUSIONS: In a group of hemodynamically stable patients with
      severe ALI, NPPV had a high success rate. NPPV should be considered as a
      treatment option for patients in stable condition in the early phase of ALI/ARDS.

PMID- 9925081
TI  - The role of anaerobes in patients with ventilator-associated pneumonia and
      aspiration pneumonia: a prospective study.
AB  - CONTEXT: Aspiration of oropharyngeal material, with its high concentration of
      anaerobic bacteria, has been implicated in the pathogenesis of both ventilator
      associated pneumonia (VAP) and aspiration pneumonitis (AP). Consequently,
      patients with these disorders are usually treated with antimicrobial agents with
      anaerobic activity. OBJECTIVE: To determine the incidence of anaerobic bacteria
      in patients with VAP and AP. DESIGN: Prospective, nonrandomized, interventional
      study. SETTING: University-affiliated community teaching hospital. PATIENTS AND
      INTERVENTIONS: We performed sequential blind protected specimen brush (PSB)
      sampling and mini-BAL in 143 patients with 185 episodes of suspected VAP and 25
      patients with AP who required mechanical ventilation. Quantitative aerobic and
      anaerobic cultures were performed on all specimens. Pneumonia was considered to
      be present when either > 500 cfu/mL cultured from blind PSB sampling or > 5,000
      cfu/mL cultured from mini-BAL were present. RESULTS: Using the predefined
      criteria, bacterial pneumonia was diagnosed in 63 of 185 suspected VAP episodes
      (34%) and 12 of 25 patients with AP (48%). At least one dose of an antibiotic was
      given in the 24 h prior to bacteriologic sampling in 106 suspected VAP episodes
      (57%) and in 12 patients with AP (48%). More than one pathogen was isolated from
      11 VAP and four AP patients. Pseudomonas aeruginosa, Staphylococcus aureus, and
      enteric Gram-negative organisms were isolated most frequently from patients with
      VAP. In the patients with AP, enteric Gram-negative organisms were isolated in
      patients with GI disorders and Streptococcus pneumoniae and Haemophilus
      influenzae predominated in patients with "community-acquired" aspiration. Only
      one anaerobic organism was isolated from the entire group of patients;
      Veillonella paravula was isolated from a blind PSB specimen in a patient with
      suspected aspiration pneumonia. CONCLUSION: Despite painstaking effort, we were
      able to isolate only one anaerobic organism (nonpathogenic) from this group of
      patients. The spectrum of aerobes in patients with VAP was similar to that
      reported in the literature. The organisms found in patients with AP was a
      reflection of the organisms likely to colonize the oropharynx. The use of
      antibiotics with anaerobic coverage may not be necessary in patients with
      suspected VAP and AP. Furthermore, penicillin G and clindamycin may not be the
      antibiotics of choice in patients with AP.

PMID- 9925082
TI  - The effect of heliox on nebulizer function using a beta-agonist bronchodilator.
AB  - OBJECTIVE: To evaluate nebulizer performance when heliox was used to power the
      nebulizer. METHODS: Conventional and continuous nebulizer designs were evaluated.
      The conventional nebulizer was used with 5 mg albuterol and flows of 8 L/min air,
      8 L/min heliox, and 11 L/min heliox; it was also used with 10 mg albuterol and a
      heliox flow of 8 L/min. The continuous nebulizer was set to deliver 10 mg of
      albuterol over 40 min at flows of 2 L/min air, 2 L/min heliox, and 3 L/min
      heliox; it was also used with 20 mg albuterol and a heliox flow of 2 L/min. A
      cotton plug at the nebulizer mouthpiece was used to trap aerosol during simulated
      spontaneous breathing. The amount of albuterol deposited on the cotton plug was
      determined spectrophotometrically. Particle size was determined using an 11-stage
      cascade impactor. RESULTS: For both nebulizer designs, particle size and inhaled
      mass of albuterol decreased significantly (p < 0.001) when the nebulizer was
      powered with heliox rather than air. When powered with heliox, the reduction in
      inhaled mass of albuterol was less for the conventional nebulizer (16%) than the
      continuous nebulizer (67%). The nebulization time, however, was more than twofold
      greater with heliox (p < 0.001). Increasing the flow of heliox increased the
      particle size (p < 0.05), inhaled mass of albuterol (p < 0.05), and inhaled mass
      of particles 1 to 5 microm (p < 0.05) to levels similar to powering the nebulizer
      with air at the lower flow. Increasing the albuterol concentration in the
      nebulizer and using the lower heliox flow increased the inhaled mass of albuterol
      (p < 0.05) while maintaining the smaller particle size produced with that flow.
      CONCLUSIONS: The use of heliox to power a nebulizer affects both the inhaled mass
      of medication and the size of the aerosol particles. The flow to power the
      nebulizer should be increased when heliox is used.

PMID- 9925083
TI  - Systemic distribution of talc after intrapleural administration in rats.
AB  - STUDY OBJECTIVES: Many reports have shown the efficacy of talc to induce an
      effective pleurodesis. However, there is little information about the side
      effects related to this sclerosing agent. The objective of this experimental
      study is to recognize the systemic distribution of talc after its instillation
      into the pleural space of rats. DESIGN: Forty animals were assigned to receive
      talc through a catheter placed in a left minimal thoracotomy. They were randomly
      divided in two groups: group 1 received 20 mg of talc and group 2 received 10 mg
      in the same total volume of 1 mL of saline solution. Half of the animals in each
      group were killed 24 h and the other half 48 h after the procedure. BAL was
      collected and histologic sections of both lungs, chest wall, liver, kidneys,
      spleen, heart, and brain were examined. Crystals were tracked using polarized
      light and we have used a "birefringent particles index of deposition" in an
      attempt to quantify the amount or talc encountered in different organs. RESULTS:
      Talc crystals were found in every organ of all animals studied (100%). There was
      no statistical difference either on the dose of talc used or in the time of
      death. The amount of talc was statistically different in the organs, which made
      us divagate about a route of absorption. CONCLUSIONS: We conclude that there is a
      progressive deposition of talc particles in the organs examined after its
      administration into the pleural space of normal rats. This report suggests that
      there is a rapid absorption of talc through the pleural surface and that the
      systemic distribution thereafter is not dose related. Further studies are
      necessary to assess the amount of crystals and the clinical correlation to these
      findings.

PMID- 9925084
TI  - Degradation of histamine solutions used for bronchoprovocation.
AB  - STUDY OBJECTIVES: To determine optimal storage conditions for histamine
      diphosphate (HDP) solutions used for bronchoprovocation. DESIGN: HDP was
      dissolved in buffered saline solution to concentrations of 0.125 to 16 mg/mL and
      stored in 3-mL unit dose syringes at different temperatures for varying lengths
      of time, with and without protection from fluorescent light. SETTING: Dark
      freezer (-20 degrees C), dark refrigerator (4 degrees C), and laboratory counter
      top (20 degrees C) illuminated by fluorescent light (375 foot-candles).
      MEASUREMENTS: HDP concentrations were measured after the solutions were prepared
      and during storage by a high-performance liquid chromatographic assay that
      differentiates histamine from its break down products. RESULTS: All dilutions
      were sterile after preparation and contained 97 to 110% of the labeled amount of
      HDP. Solutions constantly exposed to fluorescent light (375 foot-candles) and
      room temperature (20 degrees C) contained only 20 to 37% of the initial
      concentrations after 7 days. The same dilutions stored at room temperature, but
      protected from light, contained 83 to 94% of the initial concentrations.
      Dilutions stored in the dark in a refrigerator (4 degrees C) retained 97% of the
      initial concentrations after 8 weeks, while dilutions stored in the dark freezer
      (-20 degrees C) were stable for 12 months. CONCLUSIONS: Exposure to fluorescent
      light at room temperature results in degradation of histamine solutions used for
      bronchoprovocation. Dilutions stored in unit dose syringes and protected from
      light are stable for at least 8 weeks in the refrigerator and up to 12 months
      frozen. Once removed from the refrigerator or freezer, the solutions should be
      used within 6 h or discarded.

PMID- 9925085
TI  - Characterization of an animal model of ventilator-acquired pneumonia.
AB  - To develop an experimental model of ventilator-acquired pneumonia (VAP), we
      investigated whether healthy piglets could develop endogenously acquired
      pulmonary infection as a result of prolonged mechanical ventilation (MV). Thirty
      three piglets underwent MV with anesthesia, analgesia, and paralysis produced by
      continuous infusion of midazolam, fentanyl, and pancuronium bromide. Ten animals
      received antibioprophylaxis with ceftriaxone (ATB group) and 23 received no
      antibiotics (control group). Eighteen control animals and 9 ceftriaxone-treated
      animals completed the 4-day study protocol. The presence of pneumonia on day 4
      was ascertained by multiple pulmonary biopsy specimens, processed for microscopic
      examination and quantitative cultures. The anesthetic regimen provided
      satisfactory electrolyte balance and cardiovascular stability. Under these
      circumstances, 17 of 18 animals and 4 of 9 animals developed VAP in the control
      and the ATB groups, respectively. Lesions of different grades of severity were
      unevenly distributed through both lungs with a predominance and a higher severity
      in dependent lung segments. Noninfectious lesions frequently associated with VAP
      in humans were not observed. Pneumonia was usually polymicrobial with a
      predominance of Gram-negative organisms. Most of the causative organisms
      originated from the oropharynx. Histologic lesions and lung bacterial
      concentrations were less in the ATB group than in control animals. We then
      investigated the effects of intrabronchial challenge with bacterial pathogens in
      the absence of MV. Intrabronchial bacterial inoculation resulted in the
      development of pneumonia that spontaneously resolved even when using very highly
      titrated inocula. Therefore, MV seems to be the main predisposing factor in the
      development of pneumonia in this model. This model that resembles human VAP in
      its histologic, bacteriologic, and pathogenic aspects may be useful to further
      study pathogenesis, diagnosis, prevention, and therapy of VAP.

PMID- 9925086
TI  - The 1997 Asthma Management Guidelines and therapeutic issues relating to the
      treatment of asthma. National Heart, Lung, and Blood Institute.
AB  - In 1997, the National Heart, Lung, and Blood Institute released the Second Expert
      Panel Report on the Guidelines for the Diagnosis and Management of Asthma as a
      follow-up to the first report issued in 1991. Implementation of the
      recommendations from this report could have a potentially huge impact on care and
      treatment of asthma in the United States. Even though the Guidelines are
      expansive, there are some areas related to the pharmacologic component that
      warrant further discussion and clarification. These are: (1) safety and efficacy
      of available asthma medications, (2) clinical efficacy comparisons of inhaled
      corticosteroids, (3) comparative risks among inhaled corticosteroids, and (4)
      expectations of different delivery systems used with inhaled corticosteroids.

PMID- 9925087
TI  - Development of housing programs to aid in the treatment of tuberculosis in
      homeless individuals: a pilot study.
AB  - STUDY OBJECTIVES: To describe our experience with novel supervised housing
      programs developed to aid in the treatment of tuberculosis (TB) in homeless
      individuals, including a preliminary analysis of their effectiveness and estimate
      of potential cost savings. DESIGN: Retrospective chart review. SETTING: A county
      TB control program. METHODS: The San Diego County TB Control Program's computer
      database was used to identify homeless individuals placed in one of two
      supervised housing programs for treatment of TB [Young Men's Christian
      Association (YMCA), for noninfectious patients, or Bissell House, for infectious
      patients]. Charts for all these patients were reviewed and information regarding
      their demographics, underlying medical conditions, therapy, microbiologic markers
      of response to therapy, hospitalizations, and participation in supervised housing
      programs was recorded. MEASUREMENTS AND RESULTS: The sputum culture conversion
      and treatment completion rates for those housed in the YMCA were 100 and 84.6%,
      respectively. Of the patients in the Bissell House program, 100% had converted
      their smear and culture. In addition, all patients in this program completed an
      adequate course of supervised therapy. These rates of microbiologic conversion
      and treatment completion compare favorably with historical data from San Diego
      County and other locations. Estimated cost savings for placing medically stable
      infectious patients in the Bissell House for respiratory isolation and supervised
      treatment were estimated to be $27,034 per patient. CONCLUSIONS: Use of
      supervised housing to aid in treatment of TB in the homeless appears to be
      effective and results in substantial cost savings. A larger multicenter study
      should be considered to confirm these findings and better quantify the cost
      effectiveness of such programs.

PMID- 9925088
TI  - The utility of a somatostatin-type receptor binding peptide radiopharmaceutical
      (P829) in the evaluation of solitary pulmonary nodules.
AB  - OBJECTIVE: Many neoplasms including small cell cancers more densely express
      somatostatin-type receptors or more avidly bind somatostatin than granulomatous
      and other nonmalignant processes. While non-small cell neoplasms of the lung have
      not yet been shown to demonstrate this receptor expression, previous studies have
      documented non-small cell lung cancer detection with somatostatin analog
      scintigraphy. This phenomenon can be conceivably exploited utilizing technetium
      Tc-99m P829 (P829), a unique low molecular weight somatostatin-type receptor
      binding polypeptide radiopharmaceutical. The objective of this study was to
      determine the ability of P829 scintigraphy to noninvasively differentiate
      malignant and nonmalignant solitary pulmonary nodules (SPNs). METHODS: The
      radiopharmaceutical technetium 99mTc-P829 was utilized for scintigraphy including
      single photon emission computed tomography. Thirty individuals with indeterminate
      SPNs of > or = 1 cm and significant risk factors for primary lung cancer were
      identified and underwent P829 scintigraphy. Tissue diagnosis was then established
      by transthoracic needle biopsy specimens. RESULTS: Fourteen subjects demonstrated
      abnormal P829 scans in the region of the radiographic abnormality. Twelve of this
      group had biopsy specimens revealing neoplasia. Two subjects with necrotizing
      granuloma on biopsy specimen had abnormal P829 scans in the region of the nodule.
      Sixteen subjects had no abnormal P829 tracer uptake in the region of the nodule.
      Fourteen subjects had benign diagnoses on biopsy specimens. One member of this
      group with a non-diagnostic biopsy specimen refused thoracotomy and remains
      radiographically stable at 24 months of follow-up. One subject with a squamous
      cell carcinoma demonstrated no P829 activity in the region of the nodule. The
      specificity of P829 scintigraphy based on transthoracic needle biopsy specimen
      was 88%. The sensitivity was 93%. P829 scintigraphy correctly identified or
      excluded malignancy in 27 of 30 subjects. CONCLUSIONS: P829 scintigraphy reliably
      identified or excluded malignancy in radiographically indeterminate solitary
      pulmonary nodules. The sensitivity and specificity compared favorably with the
      reported results of F-18 fluorodeoxyglucose positron emission tomographic
      imaging.

PMID- 9925089
TI  - TNM staging of lung cancer: a quick reference chart.
AB  - Lung cancer is the leading cause of cancer mortalities. TNM Staging, which has
      recently been revised, remains an important guide to treatment and prognosis of
      lung cancer. In this article, we propose a simple chart that can be used as a
      quick reference consolidating all the information necessary to obtain an accurate
      staging.

PMID- 9925090
TI  - Catching patients: tuberculosis and detention in the 1990s.
AB  - The resurgence of tuberculosis (TB) in the early 1990s, including multidrug
      resistant strains, led health officials to recommend the use of involuntary
      detention for persistently nonadherent patients. Using a series of recently
      published articles on the subject, this paper offers some opinions on how
      detention programs have balanced protection of the public's health with patients'
      civil liberties. Detained persons are more likely than other TB patients to come
      from socially disadvantaged groups. Health departments have generally used
      coercion appropriately, detaining patients as a last resort and providing them
      with due process. Yet health officials still retain great authority to bypass
      "least restrictive alternatives" in certain cases and to detain noninfectious
      patients for months or years. Misbehavior within institutions may inappropriately
      be used as a marker of future nonadherence with medications. As rates of TB and
      attention to the disease again decline, forcible confinement of sick patients
      should be reserved for those persons who truly threaten the public's health.

PMID- 9925091
TI  - The 1997 International Staging System for non-small cell lung cancer: have all
      the issues been addressed?
AB  - The International Staging System for Lung Cancer has been revised recently.
      Important changes have been made to allow better correlation of prognoses and
      direction of management. The classification of synchronous pulmonary nodules in
      the same lobe as the primary tumor as T4 stage IIIB may imply a poorer outcome
      than is warranted, while the designation of a similar stage for malignant pleural
      effusion may not be reflective of the very poor prognosis associated with this
      extent of disease.

PMID- 9925092
TI  - Occupational asthma: a longitudinal study on the clinical and socioeconomic
      outcome after diagnosis.
AB  - AIM: To evaluate the clinical outcome and socioeconomic consequences of
      occupational asthma (OA). SUBJECTS AND METHODS: Twenty-five patients with OA both
      to high- and low-molecular-weight agents (3 and 22, respectively) confirmed by
      specific inhalation challenge were followed up for 12 months after the diagnosis.
      Upon diagnosis, each patient received a diary on which to report peak expiratory
      flow rate (PEFR), symptoms, drug consumption, expenses directly or indirectly
      related to the disease, as well as information regarding personal socioeconomic
      status. At each follow-up visit (1, 3, 6, and 12 months), the patients underwent
      clinical examination, spirometry, methacholine (Mch) challenge, and assessment of
      diary-derived parameters and socioeconomic status. Asthma severity (AS) was
      classified into four levels, based on symptoms, drug consumption, and PEFR
      variability. RESULTS: At 12 months, 13 patients (group A) had ceased exposure;
      the remaining 12 patients (group B) continued to be exposed. At diagnosis, FEV1
      percent and provocative dose causing a 20% fall in FEV1 (PD20) of Mch were lower
      in group A than in group B; patients of group A were also characterized by
      significantly higher basal AS levels. At 12 months, no significant variation in
      FEV1 percent or PD20 was found for either group, while AS levels improved in both
      groups, the change being more marked for group A than group B. Pharmaceutical
      expense at 12 months significantly (p < 0.05) decreased, as compared with the
      first month, in group A, whereas it tended to increase in group B. In group A, 9
      of 13 subjects had reported a deterioration of their socioeconomic status as
      compared with 2 of 12 in group B (p < 0.01). A significant loss of income was
      registered in patients of group A (median 21.45, 25th to 75th percentiles 16.9 to
      25.8 Italian liras x 10(6) on the year preceding diagnosis and 15.498, 10.65 to
      21.087 Italian liras x 10(6) on the year after diagnosis; p < 0.01), whereas no
      significant change was seen for patients in group B. CONCLUSIONS: In OA,
      cessation of exposure to the offending agent results in a decrease in asthma
      severity and in pharmaceutical expenses, but it is associated with a
      deterioration of the individual's socioeconomic status (professional downgrading
      and loss of work-derived income). There appears to be a great need for
      legislation that facilitates the relocation of these patients.

PMID- 9925093
TI  - Video-assisted thoracoscopic closure of the delayed bronchial rupture after
      thoracoscopic resection of mediastinal bronchogenic cyst.
AB  - Video-assisted thoracoscopic surgery (VATS) is an effective and less invasive
      modality for management of mediastinal disorders, but various complications can
      result from the procedure. This report describes a case of delayed rupture of the
      bronchus intermedius which occurred on postoperative day 1 after the patient
      underwent complete thoracoscopic removal of a mediastinal bronchogenic cyst (BC)
      with pericystic adhesions to the bronchus. The bronchial rupture was successfully
      treated by conventional surgical instruments through limited thoracotomy with
      video-assisted thoracoscopic guidance. In recognition of this possibility, VATS
      for a BC with adhesions should be carefully performed. Additionally, the role of
      VATS in bronchial repair is beneficial.

PMID- 9925095
TI  - A 50-year-old woman with gradual deterioration of oxygenation after lung
      transplantation.

PMID- 9925094
TI  - Clinical conference on management dilemmas: progressive pneumonia in a patient
      receiving long-term steroid therapy.

PMID- 9925096
TI  - Inability to measure lung volumes in a man with congestive heart failure.

PMID- 9925097
TI  - Multiple nodular opacities on chest radiograph after lung transplantation.

PMID- 9925098
TI  - The "fairy ring": a new radiographic finding in sarcoidosis.
AB  - A patient who had the "fairy ring" finding shows another new radiographic
      presentation of pulmonary sarcoidosis that clinicians can add to the list of
      signs of the disease.

PMID- 9925099
TI  - Successful treatment of pulmonary lymphangioleiomyomatosis with progestins: a
      case report.
AB  - The diagnostic approach, clinical evolution, and treatment of a patient with
      primary pulmonary lymphangioleiomyomatosis are reported. This patient presented a
      restrictive respiratory syndrome resistant to conventional glucocorticoid
      therapy. The diagnosis, based on clinical and histologic examinations, was
      confirmed by immunohistochemical localization of one of the desmins, the smooth
      muscle cell actin, and HMB45 antigen. The patient received treatment with an anti
      estrogenic agent (tamoxifen citrate) and high doses of medroxyprogesterone
      acetate, an antigonadotropic progestin. Respiratory function improved rapidly
      with clinical relief.

PMID- 9925100
TI  - Hemoptysis due to MDI therapy in a patient with permanent tracheostomy: treatment
      with mask AeroChamber.
AB  - Persistent minor hemoptysis resulted from extensive granulation tissue on the
      main carina and adjacent bronchi due to frequent spraying of metered-dose inhaler
      (MDI)-generated aerosol medications directly into a permanent tracheostomy.
      Salbutamol, containing oleic acid, was considered the most likely cause. After an
      AeroChamber equipped with an infant mask was interposed between the MDI and the
      tracheal stoma, hemoptysis and the pathologic changes gradually resolved.

PMID- 9925101
TI  - Two cases of repeatedly recurrent atypical thymoma.
AB  - Two cases of repeatedly recurrent thymoma with myasthenia gravis are detailed
      here. A 41-year-old woman had 5 recurrent thymomas, including local recurrences
      and lumbar and lung metastases; she was alive at the time of this writing, which
      was 22 years after her first surgery. A 36-year-old man had 3 recurrent thymomas,
      including local recurrence, dissemination, and lung metastasis; he was alive at
      the time of this writing, which was 16 years after his first surgery. Both
      recurrent lesions were diagnosed as "atypical thymoma" with moderate nuclear
      atypia. The patients with atypical thymoma must be followed up carefully due to a
      possible recurrence. Surgical treatment with chemoradiotherapy can lengthen their
      survival.

PMID- 9925102
TI  - A transitional variant of Castleman's disease presenting as a chylous pleural
      effusion.
AB  - Castleman's disease is an uncommon clinicopathologic entity that results in
      unregulated growth of lymphoid tissue. It may present as benign involvement of
      one lymph node group or as multicentric disease with serious systemic symptoms.
      Pleural effusions are an uncommon manifestation of Castleman's disease. We
      present a patient with Castleman's disease who initially presented with a chylous
      pleural effusion.

PMID- 9925103
TI  - Tension fecopneumothorax due to colonic perforation in a diaphragmatic hernia.
AB  - A traumatic diaphragmatic hernia is a well-known complication following blunt
      abdominal or penetrating thoracic trauma. Although the majority of cases are
      diagnosed immediately, some patients may present later with a diaphragmatic
      hernia. A tension fecopneumothorax, however, is a rarity. We report on a patient
      who, 2 years after being treated for a stab wound to the chest, presented with an
      acute tension fecopneumothorax caused by the incarceration of the large bowel in
      the thoracic cavity after an intrathoracic perforation. The etiology and
      management of this condition are discussed.

PMID- 9925104
TI  - Kirschner wire embolization to the heart: an unusual cause of pericardial
      tamponade.
AB  - A 50-year-old man presented with an abrupt onset of sharp, pleuritic, right-sided
      chest pain. A chest radiograph revealed a metallic foreign body over the cardiac
      silhouette; a chest CT scan localized the object to within the wall of the right
      ventricle. The patient subsequently developed pericardial tamponade necessitating
      pericardiocentesis. A 25-mm-long Kirschner wire protruding through the wall of
      the right ventricle was removed via thoracotomy. Forty-two months previously, the
      patient had undergone open reduction and fixation of a left radius fracture with
      two Kirschner wires. Clinicians caring for patients with orthopedic wires in
      place should be aware of wire migration with cardiac embolization as a potential
      complication.

PMID- 9925105
TI  - Airway obstruction arising from blood clot: three reports and a review of the
      literature.
AB  - Airway obstruction due to presence of blood clot occurs in a variety of clinical
      settings; however, it is not always preceded by hemoptysis. The impact on
      respiratory function may be minimal or result in life-threatening ventilatory
      impairment. Three illustrative cases and a comprehensive literature review are
      presented. The presence of endobronchial blood clot is suggested by the clinical
      and radiographic findings of focal airway obstruction. The diagnosis is
      established by direct endoscopic evaluation. Initial efforts at removal of the
      airway clot, if warranted, involve lavage, suctioning, and forceps extraction
      through a flexible bronchoscope. If unsuccessful, further management options
      include rigid bronchoscopy, Fogarty catheter dislodgment of the clot, and topical
      thrombolytic agents.

PMID- 9925106
TI  - Lymphangioleiomyomatosis Registry.

PMID- 9925107
TI  - Noninvasive positive pressure ventilation in the emergency department.

PMID- 9925108
TI  - Limitations to study on noninvasive ventilation.

PMID- 9925109
TI  - On perception, perspicuity, and precision.

PMID- 9925110
TI  - Objective evaluations of the results of treatment for snoring and sleep apnea.

PMID- 9925111
TI  - Ventricular tachycardia during dobutamine stress myocardial contrast imaging.

PMID- 9925112
TI  - Use of the cardiopulmonary risk index.

PMID- 9925113
TI  - Building scientific consensus: the importance of dietary fiber.

PMID- 9925114
TI  - Is it the drink or the drinker? Circumstantial evidence only raises a
      probability.

PMID- 9925115
TI  - Early iron deficiency anemia and later mental retardation.

PMID- 9925116
TI  - Effects of small-intestinal fat and carbohydrate infusions on appetite and food
      intake in obese and nonobese men.
AB  - To determine whether the satiating effects of nutrients in the small intestine
      are lower in obese than in nonobese people, 9 healthy, obese men [age: 18-33 y;
      body mass index (BMI; in kg/m2) 30.4-40.8] and 11 healthy, nonobese men (age: 18
      33 y; BMI: 19.1-26.4) received an intraduodenal infusion of saline (control),
      lipid ( 11.97 kJ/min, or 2.86 kcal/min), or glucose (11.97 kJ/min) for 120 min on
      separate days. Fullness, hunger, and nausea were assessed by visual analogue
      scales. After the infusions, a meal was offered and food intake was quantified.
      There was no difference in appetite ratings between the obese and nonobese
      subjects during the infusions, in the amount or macronutrient composition of food
      eaten after the infusions, or in the time taken to eat the meals. Both the lipid
      and glucose infusions were associated with greater fullness than the control
      infusion. The energy content of the food eaten was less after the lipid infusion
      than after either the control or glucose infusion (P < 0.01): lipid infusion
      suppressed energy intake by 22% compared with the control infusion and by 15%
      compared with the glucose infusion. Suppression of energy intake after
      intraduodenal nutrient infusions was due to slower eating (P < 0.01).
      Intraduodenal infusions of fat suppressed appetite and food intake more than did
      equienergetic infusions of carbohydrate in both obese and nonobese young men, and
      the responses to intraduodenal fat and glucose were not affected by obesity. The
      latter observation suggests that established obesity is not associated with
      reduced small-intestinal responses to dietary fat or carbohydrate.

PMID- 9925117
TI  - Changes in resting energy expenditure after weight loss in obese African American
      and white women.
AB  - BACKGROUND: Previous studies showed that resting energy expenditure (REE) is
      lower in obese African American women than in obese white women. It is unknown,
      however, whether there are racial differences in how REE responds to weight loss
      and energy restriction. OBJECTIVE: We assessed REE, body composition, and
      respiratory quotient before and after weight loss in obese black and white women.
      DESIGN: We measured REE by indirect calorimetry and body composition by
      densitometry before and after 20-24 wk of treatment with a 3870-4289-kJ/d diet.
      Subjects were 109 obese females (24 black, 85 white) with a mean (+/-SD) body
      mass index (in kg/m2) of 36.3+/-5.0, weight of 95.7+/-12.6 kg, and age of 42.3+/
      8.1 y. RESULTS: Before treatment, REE, adjusted for body composition, was
      significantly lower in black than in white subjects (P = 0.001). Black subjects
      lost significantly less weight during treatment than did white subjects (13.4+/
      5.9 kg or 14.2+/-5.7% compared with 16.4+/-5.6 kg or 17.0+/-5.7%, respectively; P
      = 0.04). Analyses that controlled for initial REE and changes in fat mass and fat
      free mass showed that blacks had significantly greater decreases in REE after
      treatment than did whites (9.9+/-7.3% compared with 6.3+/-7.4%; P = 0.02).
      CONCLUSION: This study suggests that weight loss results in greater reductions in
      REE in obese black women than in obese white women. These data underscore the
      need to consider both biological and behavioral factors when setting expectations
      and assessing outcomes for obesity treatment in African American women.

PMID- 9925118
TI  - Regional leptin kinetics in humans.
AB  - BACKGROUND: Leptin is known to be cleared by the kidney, a tissue with
      substantial leptin receptor mRNA expression; however, lung, liver, and muscle
      tissues also express leptin receptor messenger RNA and it is not known whether
      these tissues also clear leptin from the circulation. OBJECTIVE: This study was
      conducted to determine whether net leptin clearance takes place in the pulmonary,
      splanchnic, and leg tissue beds to a similar extent as in the kidney. DESIGN:
      Plasma leptin concentrations were measured in blood entering and exiting the
      renal bed, pulmonary bed, splanchnic bed, and leg in 4 groups of subjects.
      Regional plasma flow was measured in 3 of the 4 groups. RESULTS: Renal leptin
      uptake was substantial, whereas no net uptake of leptin by the splanchnic or
      pulmonary vascular beds was detected; leg tissue was a net leptin producer. Net
      leptin release by leg tissue, relative to leg adipose tissue mass, was comparable
      with that reported previously for abdominal subcutaneous adipose tissue.
      CONCLUSION: These results confirm that the kidney is a significant site of leptin
      clearance in humans, whereas pulmonary and splanchnic beds are not.

PMID- 9925119
TI  - Pentadecanoic acid in serum as a marker for intake of milk fat: relations between
      intake of milk fat and metabolic risk factors.
AB  - BACKGROUND: The fatty acid composition of the diet is known to be partially
      reflected by the fatty acid composition of serum lipids. OBJECTIVE: We examined
      whether pentadecanoic acid (15:0) in serum lipids can be used as a marker for
      intake of milk fat, the major dietary source of 15:0. We also investigated the
      relations between intake of milk fat and cardiovascular disease risk factors.
      DESIGN: Sixty-two 70-y-old men completed 7-d dietary records. The intake of milk
      products was studied in relation to the proportions of 15:0 in serum cholesterol
      esters and phospholipids, as well as to the clinical characteristics of these
      men, by using Spearman's rank correlation. RESULTS: The proportions of 15:0 in
      serum cholesterol esters were positively related to butter intake (r = 0.36. P =
      0.004) and to the total amount of fat from milk products (r = 0.46, P < 0.0001):
      15:0 in phospholipids was related to the amount of fat from milk and cream (r =
      0.34, P = 0.008) and to the total amount of fat from milk products (r = 0.34, P =
      0.008). Inverse associations were found between intake of milk products and body
      mass index, waist circumference, LDL-HDL ratio, HDL triacylglycerols, and fasting
      plasma glucose, whereas relations to HDL cholesterol and apolipoprotein A-I
      tended to be positive. CONCLUSIONS: The results suggest that 15:0 in serum can be
      used as a marker for intake of milk fat. The explanation for the inverse
      associations between the intake of milk products and certain cardiovascular risk
      factors is not known.

PMID- 9925120
TI  - Cholesterol-lowering effects of dietary fiber: a meta-analysis.
AB  - BACKGROUND: The effects of dietary soluble fibers on blood cholesterol are
      uncertain. OBJECTIVE: This meta-analysis of 67 controlled trials was performed to
      quantify the cholesterol-lowering effect of major dietary fibers. DESIGN: Least
      squares regression analyses were used to test the effect on blood lipids of
      pectin, oat bran, guar gum, and psyllium. Independent variables were type and
      amount of soluble fiber, initial cholesterol concentration, and other important
      study characteristics. RESULTS: Soluble fiber, 2-10 g/d, was associated with
      small but significant decreases in total cholesterol [-0.045 mmol L(-1).g soluble
      fiber(-1) (95% CI: -0.054, -0.035)] and LDL cholesterol [-0.057 mmol.L(-1).g(-1)
      (95% CI: -0.070, -0.044)]. The effects on plasma lipids of soluble fiber from
      oat, psyllium, or pectin were not significantly different. We were unable to
      compare effects of guar because of the limited number of studies using 2-10 g/d.
      Triacylglycerols and HDL cholesterol were not significantly influenced by soluble
      fiber. Lipid changes were independent of study design, treatment length, and
      background dietary fat content. CONCLUSIONS: Various soluble fibers reduce total
      and LDL cholesterol by similar amounts. The effect is small within the practical
      range of intake. For example, 3 g soluble fiber from oats (3 servings of oatmeal,
      28 g each) can decrease total and LDL cholesterol by approximately 0.13 mmol/L.
      Increasing soluble fiber can make only a small contribution to dietary therapy to
      lower cholesterol.

PMID- 9925121
TI  - Energy expenditure of young Polynesian and European women in New Zealand and
      relations to body composition.
AB  - BACKGROUND: Reduced energy expenditure and excessive energy intake have been
      hypothesized to cause obesity. New Zealanders of Polynesian origin have a higher
      prevalence of obesity than do those of European origin. OBJECTIVE: We
      investigated relations between components of energy expenditure and body
      composition. DESIGN: We measured total energy expenditure (TEE) and resting
      metabolic rate (RMR) in 80 young women [40 New Zealand (NZ) Polynesian and 40 NZ
      European] aged 18-27 y by the doubly labeled water method and indirect
      calorimetry, respectively. Each group was partitioned into nonobese and obese on
      the basis of percentage body fat. RESULTS: TEE and body weight were highly
      correlated in nonobese NZ Europeans (n = 23, r = 0.76, P < 0.001), obese NZ
      Europeans (r = 0.58, P = 0.016), and nonobese NZ Polynesians (n = 25, r = 0.59, P
      = 0.002) but not in obese NZ Polynesians (r = 0.11, P = 0.70). Activity energy
      expenditure (AEE = TEE - RMR) was similar in obese Polynesians and Europeans
      (mean+/-SD: 5.5+/-2.2 and 5.2+/-1.9 MJ/d, respectively), but significantly higher
      in nonobese Polynesians (5.7+/-2.5 MJ/d) than in their European counterparts
      (3.8+/-1.9 MJ/d, P = 0.005). Similar trends were seen when AEE adjusted for body
      weight and TEE/RMR were compared among the subgroups. Body weight and RMR
      together accounted for 66% of the variation in TEE for the European group but
      only 17% for the Polynesian group. CONCLUSION: Care should be taken in applying
      "Caucasian norms" relating to energy expenditure to NZ Polynesian people.

PMID- 9925122
TI  - Wine intake and diet in a random sample of 48763 Danish men and women.
AB  - BACKGROUND: Variation in diet associated with drinking patterns may explain why
      wine seems to reduce ischemic heart disease mortality. OBJECTIVE: Our objective
      was to study the association between intake of different alcoholic beverages and
      selected indicators of a healthy diet. DESIGN: This was a cross-sectional study
      conducted in Copenhagen and Aarhus, Denmark, from 1995 to 1997, and included 23
      284 men and 25 479 women aged 50-64 y. The main outcome measures were groups of
      selected foods that were indicators of a healthy dietary pattern. RESULTS: Wine,
      as compared with other alcoholic drinks, was associated with a higher intake of
      fruit, fish, cooked vegetables, salad, and the use of olive oil for cooking in
      both men and women. Men who preferred beer and spirits had odds ratios of 0.42
      (95% CI: 0.39, 0.45) and 0.51 (95% CI: 0.43, 0.60), respectively, for a high
      intake of salad compared with those who preferred wine. Higher wine intake was
      associated with a higher intake of healthy food items compared with intake of <
      or = 2.5 glasses of wine/mo; odds ratios for drinkers of between 30 and 135
      glasses of wine/mo for all the chosen indicators of healthy diet varied between
      1.23 and 4.20, and were all strongly significant. CONCLUSION: Wine drinking is
      associated with an intake of a healthy diet. This finding may have implications
      for the interpretation of previous reports of the relation between type of
      alcoholic beverage and mortality.

PMID- 9925123
TI  - Postprandial lipid, glucose, insulin, and cholecystokinin responses in men fed
      barley pasta enriched with beta-glucan.
AB  - BACKGROUND: Fiber regulates the rate and site of lipid and carbohydrate digestion
      and absorption and thus can modify the alimentary responses to a meal. When fiber
      sources containing viscous polysaccharides are included in a meal, a slower rate
      of carbohydrate and lipid absorption will modify the alimentary hormone and lipid
      responses. OBJECTIVE: We investigated in 11 healthy men the response of insulin,
      glucose, cholecystokinin, and lipid to 2 test meals containing beta-glucan.
      DESIGN: One of the meals was high in fiber (15.7 g) and the other meal was low in
      fiber (5.0 g). The low-fiber meal contained pasta made with wheat flour. The high
      fiber meals contained pasta prepared by replacing 40% of the wheat with 2 types
      of barley flour: barley naturally high in beta-glucan and the other a flour
      enriched in beta-glucan during processing. RESULTS: Plasma glucose and insulin
      concentrations increased significantly after all meals but the insulin response
      was more blunted after the barley-containing meals. The test meals were low in
      fat (25% of energy) but elicited an increase in plasma triacylglycerol and
      cholecystokinin. Cholecystokinin remained elevated for a longer time after the
      barley-containing meals. After the low-fiber meal, plasma cholesterol
      concentrations did not change significantly; however, 4 h after the barley
      containing meals, the cholesterol concentration dropped below the fasting
      concentration and was significantly lower than that after the low-fiber meal.
      CONCLUSIONS: Carbohydrate was more slowly absorbed from the 2 high-fiber meals.
      Consumption of the barley-containing meals appeared to stimulate reverse
      cholesterol transport, which may contribute to the cholesterol-lowering ability
      of barley.

PMID- 9925124
TI  - Consumption of fructooligosaccharides does not favorably affect blood glucose and
      serum lipid concentrations in patients with type 2 diabetes.
AB  - BACKGROUND: Fructooligosaccharides have been claimed to lower fasting glycemia
      and serum total cholesterol concentrations, possibly via effects of short-chain
      fatty acids produced during fermentation. OBJECTIVE: We studied the effects of
      fructooligosaccharides on blood glucose, serum lipids, and serum acetate in 20
      patients with type 2 diabetes. DESIGN: In a randomized, single-blind, crossover
      design, patients consumed either glucose as a placebo (4 g/d) or
      fructooligosaccharides (15 g/d) for 20 d each. Average daily intakes of energy,
      macronutrients, and dietary fiber were similar with both treatments. RESULTS:
      Compliance, expressed as the proportion of supplements not returned, was near
      100% during both treatments. Fructooligosaccharides did not significantly affect
      fasting concentrations (mmol/L) of serum total cholesterol (95% CI: -0.07, 0.48),
      HDL cholesterol (-0.04, 0.04), LDL cholesterol (-0.06, 0.34), serum
      triacylglycerols (-0.21, 0.44), serum free fatty acids (-0.08, 0.04), serum
      acetate (-0.01, 0.01), or blood glucose (-0.37, 0.40). CONCLUSIONS: We conclude
      that 20 d of dietary supplementation with fructooligosaccharides had no major
      effect on blood glucose, serum lipids, or serum acetate in patients with type 2
      diabetes. This lack of effect was not due to changes in dietary intake,
      insufficient statistical power, or noncompliance of the patients.

PMID- 9925125
TI  - Serum and urinary magnesium in young diabetic subjects in Bangladesh.
AB  - BACKGROUND: Magnesium imbalance, implicated in diabetes mellitus both as a cause
      and a consequence, has not yet been investigated in subgroups of subjects with
      malnutrition-related diabetes mellitus. which is prevalent in young patients in
      tropical developing countries such as Bangladesh. OBJECTIVE: The present study
      evaluated the serum and urinary magnesium concentrations in groups of young
      diabetic subjects in Bangladesh. DESIGN: Forty patients newly diagnosed with
      diabetes [13 with fibrocalculus pancreatic diabetes (FCPD), 13 with protein
      deficient diabetes (PDDM), and 14 with type 2 diabetes mellitus] were studied
      along with 13 healthy control and 13 malnourished control subjects [body mass
      index (in kg/m2) < 19]. Magnesium was measured by atomic absorption
      spectrophotometry. RESULTS: Malnutrition itself was not related to the serum
      glucose (fasting: 3.68+/-0.74 and 4.11+/-0.29 mmol/L; postprandial: 6.30+/-0.41
      and 6.00+/-0.24 mmol/L for healthy and malnourished control subjects,
      respectively) or serum or urinary magnesium (serum: 0.73+/-0.03 and 0.75+/-0.05
      mmol/L: urinary: 232+/-124 and 243+/-88 mmol Mg/mol creatinine for healthy and
      malnourished control subjects, respectively) concentration. Subjects with FCPD
      and PDDM had significantly lower serum magnesium concentrations (PDDM: 0.68+/
      0.06 mmol/L, FCPD: 0.66+/-0.07 mmol/L) than those in both control groups. In
      contrast with 0% of healthy and 7.7% of malnourished control subjects, 42.85% of
      type 2 diabetic subjects, 61.54% of those with PDDM, and 69.23% of those with
      FCPD were hypomagnesemic. Subjects with FCPD and PDDM had significantly higher
      urinary excretion of magnesium than the healthy and malnourished control subjects
      and the type 2 diabetic subjects. Hypermagnesuria paralleled hypomagnesemia.
      CONCLUSIONS: Malnutrition may not itself give rise to glucose intolerance, and
      serum magnesium deficiency seems to be a consequence rather than a cause of
      diabetes mellitus.

PMID- 9925126
TI  - Vitamin K intake and hip fractures in women: a prospective study.
AB  - BACKGROUND: Vitamin K mediates the gamma-carboxylation of glutamyl residues on
      several bone proteins, notably osteocalcin. High serum concentrations of
      undercarboxylated osteocalcin and low serum concentrations of vitamin K are
      associated with lower bone mineral density and increased risk of hip fracture.
      However, data are limited on the effects of dietary vitamin K. OBJECTIVE: We
      investigated the hypothesis that high intakes of vitamin K are associated with a
      lower risk of hip fracture in women. DESIGN: We conducted a prospective analysis
      within the Nurses' Health Study cohort. Diet was assessed in 72327 women aged 38
      63 y with a food-frequency questionnaire in 1984 (baseline). During the
      subsequent 10 y of follow-up, 270 hip fractures resulting from low or moderate
      trauma were reported. RESULTS: Women in quintiles 2-5 of vitamin K intake had a
      significantly lower age-adjusted relative risk (RR: 0.70; 95% CI: 0.53, 0.93) of
      hip fracture than women in the lowest quintile (< 109 microg/d). Risk did not
      decrease between quintiles 2 and 5 and risk estimates were not altered when other
      risk factors for osteoporosis, including calcium and vitamin D intakes, were
      added to the models. Risk of hip fracture was also inversely associated with
      lettuce consumption (RR: 0.55; 95% CI: 0.40, 0.78) for one or more servings per
      day compared with one or fewer servings per week), the food that contributed the
      most to dietary vitamin K intakes. CONCLUSIONS: Low intakes of vitamin K may
      increase the risk of hip fracture in women. The data support the suggestion for a
      reassessment of the vitamin K requirements that are based on bone health and
      blood coagulation.

PMID- 9925127
TI  - Effect of daily and weekly micronutrient supplementation on micronutrient
      deficiencies and growth in young Vietnamese children.
AB  - BACKGROUND: Micronutrient deficiencies remain common in preschool children in
      developing countries. Interventions focus on single micronutrients and often lack
      effectiveness. Weekly instead of daily supplementation may improve effectiveness.
      OBJECTIVE: The efficacy of weekly and daily supplementation in reducing anemia
      prevalence and in improving the zinc, vitamin A, and growth status of 6-24-mo-old
      Vietnamese children was investigated. DESIGN: In this double-blind, placebo
      controlled trial, the daily group (n = 55) received 8 mg elemental Fe (as iron
      sulfate), 5 mg elemental Zn (as zinc sulfate), 333 microg retinol, and 20 mg
      vitamin C 5 d/wk for 3 mo. The weekly group (n = 54) received 20 mg Fe, 17 mg Zn,
      1700 microg retinol, and 20 mg vitamin C once a week. A third group (n = 54)
      received a placebo only. Venous blood samples were collected at the start and end
      of the supplementation period and anthropometric measurements were taken at the
      start and 3 mo after the end of supplementation. RESULTS: At baseline, 45.6% of
      subjects had hemoglobin concentrations < 110 g/L, 36.3% had zinc concentrations <
      10.71 micromol/L, and 45.6% had retinol concentrations <0.70 micromol/L.
      Hemoglobin, retinol, and zinc concentrations of both the weekly and daily groups
      increased similarly compared with the placebo group (P < 0.001). There was no
      significant difference in growth between the supplemented groups and the placebo
      group. However, the height-for-age of subjects stunted at baseline increased with
      z scores of 0.48 (P < 0.001) and 0.37 (P < 0.001) for the daily and weekly
      groups, respectively. CONCLUSIONS: Weekly and daily supplementation improved
      hemoglobin, zinc, and retinol concentrations similarly. Neither intervention
      affected growth of the overall population, but growth of children stunted at
      baseline was improved through both types of supplementation.

PMID- 9925128
TI  - Effect of fruit juice intake on urinary quercetin excretion and biomarkers of
      antioxidative status.
AB  - BACKGROUND: Epidemiologic studies suggest that foods rich in flavonoids might
      reduce the risk of cardiovascular disease. OBJECTIVE: Our objective was to
      investigate the effect of intake of flavonoid-containing black currant and apple
      juice on urinary excretion of quercetin and on markers of oxidative status.
      DESIGN: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL)
      consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4,
      and 9.6 mg quercetin/d. RESULTS: Urinary excretion of quercetin increased
      significantly with dose and with time. The fraction excreted in urine was 0.29
      0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate
      increased during intervention because of the ascorbate in the juice. Total plasma
      malondialdehyde decreased with time during the 1500-mL juice intervention,
      indicating reduced lipid oxidation in plasma. Plasma 2-amino-adipic semialdehyde
      residues increased with time and dose, indicating a prooxidant effect of the
      juice, whereas erythrocyte 2-aminoadipic semialdehyde and gamma-glutamyl
      semialdehyde concentrations, Trolox-equivalent antioxidant capacity, and ferric
      reducing ability of plasma did not change. Glutathione peroxidase activity
      increased significantly with juice dose. CONCLUSIONS: Urinary excretion of
      quercetin seemed to be a small but constant function of quercetin intake. Short
      term, high intake of black currant and apple juices had a prooxidant effect on
      plasma proteins and increased glutathione peroxidase activity, whereas lipid
      oxidation in plasma seemed to decrease. These effects might be related to several
      components of the juice and cannot be attributed solely to its quercetin content.

PMID- 9925129
TI  - Bioavailability of vitamin D from wild edible mushrooms (Cantharellus
      tubaeformis) as measured with a human bioassay.
AB  - BACKGROUND: The bioavailability of vitamin D from mushrooms in humans is unknown.
      OBJECTIVE: We investigated the bioavailability of vitamin D from wild edible
      mushrooms (Cantharellus tubaeformis) using the increase in serum 25
      hydroxyvitamin D concentrations as a measure of vitamin D bioavailability.
      DESIGN: Twenty-seven volunteers with serum 25-hydroxyvitamin D concentrations <60
      nmol/L (mean : 38.5 nmol/L; range: 15-60 nmol/L) were randomly divided into 3
      groups of 9 persons each. For 3 wk, excluding Saturdays and Sundays, group 1
      received mushrooms (C. tubaeformis) providing 14 microg ergocalciferol/d with
      their lunch, group 2 (control) received an ergocalciferol supplement providing 14
      microg/d, and group 3 (also a control) received no supplementation. RESULTS: At
      the beginning of the study, mean serum 25-hydroxyvitamin D concentrations did not
      differ significantly among the groups (P = 0.280). When all 3 groups were
      considered, serum 25-hydroxyvitamin D concentrations showed different time
      related changes among the groups during the study: group (P = 0.388), time (P =
      0.000), and group x time (P = 0.001). When groups 1 and 2 were compared with
      group 3, serum 25-hydroxyvitamin D concentrations at 3 wk differed significantly
      between groups 1 and 3 (P = 0.032) as well as between groups 2 and 3 (P = 0.004).
      Serum 25-hydroxyvitamin D concentrations at 3 wk did not differ significantly
      between groups 1 and 2 (P = 0.317). CONCLUSIONS: We showed for the first time
      that ergocalciferol was well absorbed from lyophilized and homogenized mushrooms
      in humans and that vitamin D bioavailability can be studied in humans with such
      an experimental protocol.

PMID- 9925130
TI  - Low-dose folic acid supplementation decreases plasma homocysteine concentrations:
      a randomized trial.
AB  - BACKGROUND: An elevated plasma total homocysteine concentration is a risk factor
      for cardiovascular disease and neural tube defects. A high daily intake of
      supplemental folic acid is known to decrease total homocysteine concentrations.
      OBJECTIVE: We studied the effect of low-dose folic acid administration (250 or
      500 (microgram/d) for 4 wk on plasma total homocysteine concentrations and folate
      status. We also investigated whether total homocysteine concentrations and blood
      folate concentrations returned to baseline after an 8-wk washout period. DESIGN:
      In this placebo-controlled study, 144 healthy women aged 18-40 y received 500
      microgram folic acid/d, 500 microgram folic acid every second day (250
      microgram/d), or a placebo tablet with their habitual diet (mean dietary folate
      intake: 280 microgram/d). RESULTS: Administration of 250 and 500 microgram folic
      acid/d for 4 wk significantly increased folate concentrations in plasma (P <
      0.001) and red blood cells (P < 0.01). Total homocysteine concentrations
      decreased significantly (P < 0.001) in women (n = 50) who took 250 microgram
      folic acid/d [mean (+/-SEM) deviation from baseline: - 11.4 +/- 198%] and in
      women (n = 45) who took 500 microgram folic acid/d (-21.8 + 1.49%). Eight weeks
      after the end of the intervention period (week 12), plasma total homocysteine
      concentrations in the folic acid-supplemented groups had not returned to baseline
      (week 0). CONCLUSIONS: Doses of folic acid as low as 250 microgram/d, on average,
      in addition to usual dietary intakes of folate significantly decreased plasma
      total homocysteine concentrations in healthy, young women. An 8-wk washout period
      was not sufficient for blood folate and plasma total homocysteine concentrations
      to return to baseline concentrations.

PMID- 9925131
TI  - Threonine kinetics in preterm infants fed their mothers' milk or formula with
      various ratios of whey to casein.
AB  - BACKGROUND: Plasma threonine concentrations are elevated in infants fed formula
      containing a whey-to-casein protein ratio of 60:40 compared with concentrations
      in infants fed formula containing a ratio of 20:80 or human milk (60:40).
      OBJECTIVE: We studied whether degradation of excess threonine was lower in
      formula-fed infants than in infants fed their mothers' milk. DESIGN: Threonine
      kinetics were examined in 17 preterm infants (gestational age: 31+/-2 wk: birth
      weight: 1720+/-330 g) by using an 18-h oral infusion of [1-13C]threonine at a
      postnatal age of 21+/-11 d and weight of 1971+/-270 g. Five infants received
      breast milk. Formula-fed infants (n = 12) were randomly assigned to receive 1 of
      3 formulas (5.3 g protein/MJ) that differed only in the whey-to-casein ratio
      (20:80, 40:60, and 60:40). RESULTS: Threonine intake increased significantly in
      formula-fed infants with increasing whey content of the formula (48.5, 56.4, and
      63.2 micromol.kg(-1).h(-1), respectively; pooled SD: 2.2; P = 0.0001), as did
      plasma threonine concentrations (228, 344, and 419 micromol/L, respectively;
      pooled SD: 75; P = 0.03). Despite a generous threonine intake by infants fed
      breast milk (58.0+/-16.0 micromol.kg(-1).h(-1), plasma threonine concentrations
      remained low (208+/-41 micromol/L). Fecal threonine excretion and net threonine
      tissue gain, estimated by nitrogen balance, did not differ significantly among
      groups. Threonine oxidation did not differ significantly among formula-fed
      infants but was significantly lower in formula-fed infants fed than in infants
      fed breast milk (17.1% compared with 24.3% of threonine intake, respectively).
      CONCLUSION: Formula-fed infants have a lower capacity to oxidize threonine than
      do infants fed breast milk.

PMID- 9925132
TI  - Early childhood anemia and mild or moderate mental retardation.
AB  - BACKGROUND: Previous studies questioned the link between early childhood anemia
      and detrimental child development. OBJECTIVE: A population-based study was
      conducted to examine the association between early childhood anemia and mild or
      moderate metal retardation at 10 y of age. DESIGN: The present study linked early
      childhood nutrition data collected by the Special Supplemental Program for Women,
      Infants, and Children (WIC) and school records. Hemoglobin values were used to
      determine the relation between anemia in early life and children's placement in
      special education classes for mild or moderate mental retardation. Subjects were
      all participants in the WIC program. A computer program was used to link data
      from birth, WIC, and school records. RESULTS: Logistic regression showed an
      increased likelihood of mild or moderate mental retardation associated with
      anemia, independent of birth weight, maternal education, sex, race-ethnicity, the
      mother's age, or the child's age at entry into the WIC program. CONCLUSION: These
      findings support the proposition that efforts to prevent mild and moderate mental
      retardation should include providing children with adequate nutrition during
      early childhood.

PMID- 9925133
TI  - Diet, physical activity, and gallstones--a population-based, case-control study
      in southern Italy.
AB  - BACKGROUND: Gallstones are a highly prevalent condition; however, the nutritional
      and lifestyle risk factors of this disease are not well understood. OBJECTIVE: We
      evaluated the association between diet, physical activity, and incident cases of
      gallstones diagnosed by ultrasound in a population-based, case-control study.
      DESIGN: One hundred patients with newly diagnosed gallstones and 290 randomly
      selected control subjects without gallstones were enrolled in the study. The
      presence of gallstones was determined by ultrasonography. Both patients and
      control subjects completed a questionnaire about their usual diet and physical
      activity for the 12 mo before the ultrasonography. The association between diet
      and physical activity and risk of gallstone formation was analyzed by using
      multiple logistic regression. RESULTS: Body mass index and intake of refined
      sugars were directly associated with risk of gallstone formation, whereas
      physical activity, dietary monounsaturated fats, dietary cholesterol, and dietary
      fibers from cellulose were inversely associated with risk of gallstone formation.
      Saturated fats were a risk factor for gallstone formation and the association
      appeared to be stronger for men than for women. CONCLUSION: These findings
      suggest that a sedentary lifestyle and a diet rich in animal fats and refined
      sugars and poor in vegetable fats and fibers are significant risk factors for
      gallstone formation.

PMID- 9925134
TI  - Fat malabsorption in cystic fibrosis patients receiving enzyme replacement
      therapy is due to impaired intestinal uptake of long-chain fatty acids.
AB  - BACKGROUND: Pancreatic enzyme replacement therapy frequently fails to correct
      intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The
      reason for this failure is unknown. OBJECTIVE: We investigated whether fat
      malabsorption in CF patients treated with pancreatic enzymes is caused by
      insufficient lipolysis of triacylglycerols or by defective intestinal uptake of
      long-chain fatty acids. DESIGN: Lipolysis was determined on the basis of breath
      13CO2 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy
      after they ingested 1.3-distearoyl,2[1-13C]octanoyl glycerol ([13C]MTG).
      Intestinal uptake of long-chain fatty acids was determined by analyzing plasma
      [13C]linoleic acid ([13C]LA) concentrations after patients ingested [13C]LA. For
      3 d, dietary intakes were recorded and feces were collected. RESULTS: Fecal fat
      excretion ranged from 5.1 to 27.8 g/d (mean+/-SD: 11.1+/-7.0 g/d) and fat
      absorption ranged from 79% to 93% (89+/-5%). There was no relation between breath
      13CO2 recovery and dietary fat absorption (r = 0.04) after ingestion of [13C]MTG.
      In contrast, there was a strong relation between 8-h plasma [13C]LA
      concentrations and dietary fat absorption (r = 0.88, P < 0.001). CONCLUSION: Our
      results suggest that continuing fat malabsorption in CF patients receiving enzyme
      replacement therapy is not likely due to insufficient lipolytic enzyme activity,
      but rather to incomplete intraluminal solubilization of long-chain fatty acids,
      reduced mucosal uptake of long-chain fatty acids, or both.

PMID- 9925135
TI  - Gas production in human ingesting a soybean flour derived from beans naturally
      low in oligosaccharides.
AB  - BACKGROUND: Ingestion of soy products may cause excessive intestinal gas. This
      gas results from colonic bacterial fermentation of the indigestible
      oligosaccharides raffinose and stachyose, which are present in high
      concentrations in legumes. OBJECTIVE: The objective of the study was to compare
      gas production and gaseous symptoms in healthy volunteers after ingestion of 34
      and 80 g soy flour made from either conventional soybeans or soybeans naturally
      low in indigestible oligosaccharides. DESIGN: In a double-blind, randomized,
      crossover protocol, breath hydrogen (an indicator of carbohydrate malabsorption),
      flatus frequency, and abdominal symptoms were assessed after subjects ingested
      the soy products and after 2 control meals (rice or lactose-hydrolyzed milk).
      RESULTS: The sum of breath-hydrogen concentrations for 8 h was significantly
      greater (P < 0.005) after 34 g conventional soy (60.4+/-9.4 ppm) than after low
      oligosaccharide soy (34.3+/-8.1 ppm). Greater differences were observed with 80-g
      doses: 157.9+/-19.4 ppm after conventional soy and 50.8+/-6.8 ppm after low
      oligosaccharide soy (P < 0.001). Flatus frequency (7.5+/-1.9 times/12 h) was
      significantly greater (P = 0.039) after ingestion of 80 g conventional soy than
      after the control, rice meal (3.2+/-0.8 times/12 h), whereas flatus frequency
      after the low-oligosaccharide soy meal (3.9+/-0.7 times/12 h) was comparable with
      that after the rice meal. There were no significant differences in the severity
      of other abdominal symptoms. CONCLUSION: Soy flour derived from low
      oligosaccharide soybeans resulted in less gas production than that derived from
      conventional soybeans.

PMID- 9925136
TI  - A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose
      intolerance.
AB  - BACKGROUND: Lactose intolerance is the most common disorder of intestinal
      carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of
      lactobacilli with properties of marked intestinal adherence and high beta
      galactosidase activity. OBJECTIVE: This study was designed to determine whether
      oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant
      state. DESIGN: We studied 42 subjects with self-reported lactose intolerance and
      performed breath-hydrogen tests to determine whether they were lactose
      maldigesters. Subjects with established lactose maldigestion (n = 24) were
      invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group
      or a non-omeprazole-treated group, but 6 subjects chose not to participate. All
      randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4
      twice per day for 7 d and stool samples were collected. Breath-hydrogen tests
      were performed and symptom scores were recorded at baseline and after
      lactobacilli ingestion. RESULTS: Lactose maldigestion was established in 24 of 42
      subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting
      subjects, overall hydrogen production and symptom scores after ingestion of
      Lactobacillus acidophilus BG2FO4 were not significantly different from baseline
      values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from
      7 subjects. CONCLUSIONS: Lactose intolerance is overreported in subjects with
      gastrointestinal symptoms after lactose ingestion. Treatment of lactose
      maldigesting subjects with and without hypochlorhydria with Lactobacillus
      acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion
      significantly after lactose ingestion.

PMID- 9925137
TI  - Prospective study of dietary protein intake and risk of hip fracture in
      postmenopausal women.
AB  - BACKGROUND: The role of dietary protein intake in osteoporosis remains
      controversial. Protein is an important structural component of bone and protein
      supplementation improves the medical outcome of hip fracture patients, but it is
      unknown whether protein intake can reduce the incidence risk of hip fracture.
      OBJECTIVE: The relation between intake of protein and other nutrients and
      subsequent incidence of hip fracture was evaluated. DESIGN: Nutrient intake was
      assessed with a food-frequency questionnaire in a cohort of Iowa women aged 55-69
      y at baseline in 1986. Incident hip fractures were ascertained through follow-up
      questionnaires mailed to participants in 1987 and 1989 and verified by physician
      reports. RESULTS: Forty-four cases of incident hip fractures were included in the
      analyses of 104338 person-years (the number of subjects studied times the number
      of years of follow-up) of follow-up data. The risk of hip fracture was not
      related to intake of calcium or vitamin D, but was negatively associated with
      total protein intake. Animal rather than vegetable sources of protein appeared to
      account for this association. In a multivariate model with inclusion of age, body
      size, parity, smoking, alcohol intake, estrogen use, and physical activity, the
      relative risks of hip fracture decreased across increasing quartiles of intake of
      animal protein as follows: 1.00 (reference), 0.59 (95% CI: 0.26, 1.34), 0.63
      (0.28, 1.42), and 0.31 (0.10, 0.93); P for trend = 0.037. CONCLUSION: Intake of
      dietary protein, especially from animal sources, may be associated with a reduced
      incidence of hip fractures in postmenopausal women.

PMID- 9925138
TI  - Microalbuminuria, glomerular filtration rate, and dietary fat and protein intakes
      in type 1 diabetes.

PMID- 9925139
TI  - Whole-body bone mineral content in premature infants measured at full-term age.

PMID- 9925140
TI  - Evaluation of vitamin E potency.

PMID- 9925141
TI  - Definition of sensitivity and specificity.

PMID- 9925142
TI  - Seasonal vitamin D in African American and white infants.

PMID- 9925143
TI  - An overview of the National Kidney Foundation-Dialysis Outcomes Quality
      Initiative Implementation.
AB  - Rigorously developed clinical practice guidelines have the potential to improve
      outcomes and favorably alter practice patterns. Because of widespread community
      concerns over the quality of dialysis care, the National Kidney Foundation
      initiated a Dialysis Outcomes Quality Initiative (NKF-DOQI) in March 1995 in an
      effort to create evidence-based best-practice clinical guidelines. Independent
      interdisciplinary Work Groups reviewed the available body of scientific
      literature on four selected topics: hemodialysis adequacy, peritoneal dialysis
      adequacy, vascular access, and anemia. More than 11,000 publications were
      identified, of which 1,500 were considered relevant and were subjected to
      structured review. Draft guidelines, with supporting rationales of their
      evidentiary basis, were subjected to a three-stage public and organizational
      review process. The final guidelines were issued in the fall of 1997. Because the
      potential benefit of guidelines depends on their implementation, planning for the
      implementation of NKF-DOQI was begun simultaneously with its review process. A 3
      year implementation plan, with specific priorities and estimated costs, was
      developed and set into action by the end of 1997. The main objectives of the
      rather diverse and multifaceted plan of action are translating the NKF-DOQI
      Guidelines into clinical practice, building on what has been accomplished, and
      continued evaluation and review of the Guidelines.

PMID- 9925144
TI  - Implementation of the Peritoneal Dialysis Adequacy Guidelines: a personal
      perspective.
AB  - I describe some of the political issues surrounding the National Kidney
      Foundation-Dialysis Outcomes Quality Initiative project as I perceived them. I
      then discuss what I would do differently, what I recommend to encourage
      implementation, and why regulatory concerns are well founded. I close with
      technical issues including expansion, simplification, and corrections.

PMID- 9925145
TI  - Implementation of the Dialysis Outcomes Quality Initiative Vascular Access
      Guidelines.
AB  - To better care for patients with chronic renal failure and end-stage renal
      disease, the National Kidney Foundation has published a set of Clinical
      Guidelines, the Dialysis Outcomes Quality Initiative, based on current available
      evidence and, where such evidence is lacking, the expert opinions of current
      leaders in vascular access research. These Guidelines were developed to
      standardize the care of chronic renal failure and end-stage renal disease
      patients. This report describes some of the more important aspects of these
      recommendations and the authors' implementation strategies.

PMID- 9925146
TI  - Implementation of the Anemia Guidelines.
AB  - Implementation of the National Kidney Foundation-Dialysis Outcomes Quality
      Initiative (NKF-DOQI) Guidelines for the treatment of the anemia of chronic renal
      failure is a great challenge to all concerned with the improvement in the quality
      of life and survival of patients with chronic renal failure. These include
      physicians, nurses, technicians, dietitians, social workers, administrators, and
      private and public (Health Care Financing Administration) payers of the care. The
      principles of the process of implementation are reviewed and the barriers that
      can prevent implementation are discussed, showing how most of these can be
      overcome. Several of the more controversial Guidelines are discussed in detail,
      showing that with protocols that address the means for implementation, the goals
      of these Guidelines can be achieved.

PMID- 9925148
TI  - The importance of performance evaluation in implementation of the Dialysis
      Outcomes Quality Initiative Guidelines.
AB  - To determine the extent to which actual practices become more consistent over
      time with those advocated in Dialysis Outcomes Quality Initiative Guidelines,
      clinical performance measures (CPMs) that are based on the DOQI Guidelines will
      need to be developed and implemented. CPMs also can be used to evaluate the
      effectiveness of interventions that are undertaken to promote compliance with
      specific Guideline recommendations, to validate DOQI Guidelines that were based
      in whole or in part on expert opinion, and to protect against erosion of the
      quality of care delivered to end-stage renal disease patients that could occur as
      a result of economic pressures. To achieve these goals, CPMs must be valid,
      reliable, and practical to use. A federally sponsored effort to develop such CPMs
      is currently underway. This report presents an overview of CPMs and the
      challenges involved in developing technically sound specifications for CPMs that
      are based on DOQI guidelines.

PMID- 9925147
TI  - Forum of the End-Stage Renal Disease Networks' role in implementing the National
      Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical Practice
      Guidelines.
AB  - The development and release of the National Kidney Foundation-Dialysis Outcomes
      Quality Initiative (NKF-DOQI) Clinical Practice Guidelines marks an important
      step in the on-going process of improving the renal dialysis patient's outcomes.
      The Forum of End-Stage Renal Disease (ESRD) Networks' role in this process should
      be considered within the context of its mission and the ESRD Networks'
      Congressional mandate. In addition, facilitating the implementation of the NKF
      DOQI Guidelines is one component of the Forum's current quality-related agenda.
      Environmental trends and current research indicate a variety of factors critical
      to the successful implementation of the NKF-DOQI Guidelines. The Forum's plan
      encompasses each of the following key elements: defining and evaluating the
      Guidelines and clinical performance measures (CPMs); prioritizing and locally
      disseminating NKF-DOQI Guidelines; converting NKF-DOQI Guidelines into CPMs;
      expanding the information infrastructure; and conducting quality activities and
      engaging local physicians. Keeping in mind the broader national agenda for
      quality improvement in the renal community, including continuing medical
      education programs focused on quality measurement and improvement tools and
      techniques, developing decision support tools and increasing on-line access to
      evidence-based reports and literature is important as well. Carrying out the
      Forum's plan for implementing the NKF-DOQI Guidelines, in collaboration with
      national nephrology professional and patient organizations, will facilitate
      Guideline adoption and use across the renal community.

PMID- 9925149
TI  - The role of the health care team in the implementation of the National Kidney
      Foundation-Dialysis Outcomes Quality Initiative: a case study.
AB  - The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI)
      provides an opportunity to review multidisciplinary practice in end-stage renal
      disease settings across the country. The role of the nephrology nurse, nephrology
      technician, renal dietitian, and nephrology social worker are reviewed through a
      case presentation referencing NKF-DOQI Guidelines. Each discipline provides an
      overview of its respective assessments and interventions focused on improving the
      patient's outcome.

PMID- 9925150
TI  - The role of patients in the implementation of the National Kidney Foundation
      Dialysis Outcomes Quality Initiative.
AB  - Patients have a fundamental right to be involved in making decisions that affect
      their health care treatment and outcomes. Patients need to be knowledgeable about
      disease process and treatment options to exercise this right. The National Kidney
      Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice
      Guidelines on Hemodialysis Adequacy, Peritoneal Dialysis Adequacy, Treatment of
      Anemia of Chronic Renal Failure, and Vascular Access, introduced in 1997, include
      new clinical recommendations that may impact patient treatment choices. Access to
      these guidelines presents a unique professional opportunity to empower patients
      through education related to NKF-DOQI. This article highlights the role of
      patients in implementing NKF-DOQI in light of studies conducted by two renal
      patient organizations, the National Kidney Foundation (NKF) and the American
      Association of Kidney Patients (AAKP). Results from the AAKP survey indicate that
      end-stage renal disease patients are willing to change behavior to feel better
      and live longer. Results from the NKF focus study show that dialysis patients
      need to receive information about NKF-DOQI and understand its direct impact on
      patient outcomes. In addition, results from both studies reveal that patients
      feel strongly about participating in health care decisions that impact on their
      treatment and outcomes.

PMID- 9925151
TI  - The role of providers in implementation of the National Kidney Foundation
      Dialysis Outcomes Quality Initiative: Fresenius Medical Care North America
      perspective.
AB  - This is a brief review of the history of utilization of quality indicators by a
      major dialysis provider and how those indicators have been modified in response
      to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF
      DOQI). Fresenius Medical Care North America (FMCNA) has monitored adequacy of
      dialysis, anemia management, and nutrition therapy for a number of years, using a
      self-directed continuous quality improvement program. FMCNA supports the NKF-DOQI
      Guidelines and has used the DOQI as it continues to enhance its patient quality
      care program. Specific goals and action thresholds of that program are
      delineated.

PMID- 9925152
TI  - The cost of implementing the Dialysis Outcomes Quality Initiative Clinical
      Practice Guidelines.
AB  - For a clinical practice guideline to be accepted by the end-user, the system of
      reimbursement for the targeted service must be favorable. The National Kidney
      Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Guideline
      recommendations were developed without primary concern for the costs of their
      execution. Arguably, an unfavorable financial environment and excessive
      mercantile behavior by providers and payers would offer a considerable hindrance
      to their implementation. Toward addressing these concerns, three leaders in the
      development of the DOQI Guidelines for the Treatment of Anemia of Chronic Renal
      Failure, Hemodialysis Adequacy, and Vascular Access, have evaluated the
      hypothesis that implementing the recommendations of the DOQI Guidelines will
      increase the treatment costs for dialysis providers but will effect savings in
      the entire end-stage renal disease (ESRD) program. Their analyses suggest that
      under the current reimbursement system, this assumption may be true. However,
      restructured global reimbursement in the ESRD program will permit financial
      incentives for dialysis providers and the payer to coincide.

PMID- 9925153
TI  - Blood flow rate: an important determinant of urea clearance and delivered Kt/V.
AB  - Implementation of the Dialysis Outcomes Quality Initiative (DOQI) Guidelines for
      hemodialysis adequacy will necessitate an increase in delivered Kt/V for many
      patients. Before increasing Kt/V by prolonging the patient's treatment time, it
      is important to verify that the prescribed dialyzer urea clearance is being
      achieved. The principal determinant of dialyzer urea clearance is blood flow
      rate. Actual blood flow rates are frequently less than the nominal blood flow
      rate displayed by the dialysis machine, particularly at higher flow rates,
      leading to lower than expected urea clearances. The major reason for the
      reduction in blood flow rate is a low pressure in the arterial blood line
      proximal to the blood pump. This effect can be mitigated by the use of large bore
      access needles. For quality assurance purposes, actual blood flow rates should be
      determined by correcting nominal blood flow rates for pressure effects using
      empirical relationships or by using an ultrasonic flow meter. Because a poorly
      functioning blood access may further reduce the effective blood flow rate, blood
      access performance should also be monitored regularly.

PMID- 9925154
TI  - Practical guide to measuring adequacy of dialysis.
AB  - Measurement of adequacy of small solute clearance on hemodialysis (HD) and
      peritoneal dialysis (PD) is important. In HD, formal urea kinetic modelling (UKM)
      is recommended because it is theoretically more accurate than the urea reduction
      ratio (URR) and because it allows prospective selection of an adequate
      prescription. However, the URR is simpler and has an important role to play.
      Precise attention to the methodology of sampling the post-HD blood urea is
      important. In PD, both Kt/V and creatinine clearance should be measured, and the
      main concerns relate to logistic problems in collection and processing of
      dialysate samples. In both HD and PD, a well-defined standardized methodology for
      measuring adequacy indices should be in place in each dialysis unit.

PMID- 9925155
TI  - The effect of blood draw methodology on selected nutritional parameters in
      chronic renal failure.
AB  - The reliability and validity of any clinical laboratory test is directly affected
      by the integrity of the blood specimen obtained for analysis. Renal failure
      patients undergo a high number of laboratory tests, primarily to monitor the
      quality of care. Subsequent tests to confirm laboratory abnormalities are costly
      and place the patient at unnecessary risk for additional blood loss. Three of the
      four Health Care Financing Administration core clinical outcome indicators have
      nutritional implications and use laboratory values as part of review criteria:
      adequacy of dialysis, albumin, and anemia. National Kidney Foundation-Dialysis
      Outcomes Quality Initiative (DOQI) Clinical Practice Guidelines have recommended
      standardized predialysis and postdialysis blood draw procedures to increase
      accuracy for adequacy of dialysis. The National Committee on Clinical Laboratory
      Standards publishes peer-reviewed guidelines for venipuncture. Together, the
      adoption of these standards would minimize preanalytical variation and improve
      the data used to monitor the quality of care in renal patients.

PMID- 9925156
TI  - Optimizing vascular access: a team perspective using the National Kidney
      Foundation-Dialysis Outcomes Quality Initiative Guidelines.
AB  - The implementation of the Dialysis Outcomes Quality Initiative (DOQI) Vascular
      Access Guidelines can appear as an overwhelming task. This article suggests very
      basic and practical actions the entire end-stage renal disease (ESRD) team can
      take to help put the DOQI Guidelines into every day practice. The simple format
      of an early prerenal education program may help increase the number of native
      arterio-venous fistula placed in new ESRD patients. The focus is on the ESRD team
      working together to remove common barriers preventing the implementation of the
      DOQI Guidelines. Examples about the role the social worker and renal dietitian
      can fulfill as part of the Guideline implementation are presented. This article
      is based on previous personal work experience as a member of the ESRD Team and as
      a Work Group Member.

PMID- 9925157
TI  - The impact of the Dialysis Outcomes Quality Initiative Guidelines on the care of
      the pediatric end-stage renal disease patient.
AB  - The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI)
      Guidelines for hemodialysis and peritoneal dialysis adequacy, management of
      vascular access, and management of anemia are based primarily on evidence derived
      from the experience of adult dialysis patients. However, these Guidelines can
      also be used to improve the care of children with end-stage renal disease (ESRD).
      Some of the guidelines are directly applicable to pediatric dialysis patients,
      such as the preferential use of the internal jugular vein for placement of a
      central venous catheter for dialysis. Other Guidelines, such as targets for
      adequacy of hemodialysis and peritoneal dialysis, serve as minimal standards of
      care for children with little supporting data specific to pediatrics. The
      importance of early referral and proactive care for children and adults with
      chronic renal failure is emphasized in all of the Guidelines. Optimum care should
      include early discussion of transplantation and choice of dialysis modality,
      preservation of sites for future vascular access, and early attention to anemia
      and nutrition. Clinical algorithms should be developed to implement the current
      Guidelines while data are generated to support modification of any of the
      recommendations for children.

PMID- 9925158
TI  - Vaccine coverage.

PMID- 9925159
TI  - More on measles.

PMID- 9925160
TI  - Procter & Gamble responds on olestra.

PMID- 9925161
TI  - Photo was "right on".

PMID- 9925163
TI  - Report calls for managed health care to be shaped to children's needs.

PMID- 9925162
TI  - IOM on core functions.

PMID- 9925164
TI  - Not all health plan consumers protected equally, study finds.

PMID- 9925165
TI  - Graduate education programs in life sciences should curtail growth.

PMID- 9925166
TI  - US, Russia collaborate on post-traumatic stress.

PMID- 9925167
TI  - Public health officials to get new communication tools.

PMID- 9925169
TI  - Brundtland's World Health Organization: a test case for United Nations reform.
AB  - Gro Harlem Brundtland, who became Director General of the World Health
      Organization in July 1998, has created a small revolution at the WHO headquarters
      in Geneva. She is in the process of changing how WHO works, how it interacts with
      other parts of the United Nations system, and how it enlists ministries, whole
      governments, universities, and other private organizations to improve health in
      the world. Here, the Editor describes the reorganization, the new people and
      resources, and prospects for setting a precedent in United Nations reform.

PMID- 9925168
TI  - Drug prohibition and public health: 25 years of evidence.
AB  - FOR THE PAST 25 YEARS, the US has pursued a drug policy based on prohibition and
      the vigorous application of criminal sanctions for the use and sale of illicit
      drugs. The relationship of a prohibition-based drug policy to prevalence patterns
      and health consequences of drug use has never been fully evaluated. To explore
      that relationship, the author examines national data on the application of
      criminal penalties for illegal drugs and associated trends in their patterns of
      use and adverse health outcomes for 1972-1997.Over this 25-year period, the rate
      at which criminal penalties are imposed for drug offenses has climbed steadily,
      reaching 1.5 million arrests for drug offenses in 1996, with a tenfold increase
      in imprisonment for drug charges since 1979. Today, drug enforcement activities
      constitute 67% of the $16 billion Federal drug budget and more than $20 billion
      per year in state and local enforcement expenditures, compared with $7.6 billion
      for treatment, prevention, and research.Despite an overall decline in the
      prevalence of drug use since 1979, we have seen dramatic increases in drugrelated
      emergency department visits and drug-related deaths coinciding with this period
      of increased enforcement.Further, while black, Hispanic, and white Americans use
      illegal drugs at comparable rates, there are dramatic differences in the
      application of criminal penalties for drug offenses. African Americans are more
      than 20 times as likely as whites to be incarcerated for drug offenses, and drug
      related emergency department visits, overdose deaths, and new HIV infections
      related to injecting drugs are many times higher for blacks than whites.These
      outcomes may be understood as public health consequences of policies that
      criminalize and marginalize drug users and increase drug-related risks to life
      and health.

PMID- 9925170
TI  - Can a community inject public health values into transportation questions?

PMID- 9925171
TI  - Injuries associated with snowmobiles, Alaska, 1993-1994.
AB  - OBJECTIVE: To characterize the nature and burden of snowmobile injuries in Alaska
      by examining injury deaths and hospitalizations associated with snowmobiles and
      comparing these with injury deaths and hospitalizations associated with on-road
      motor vehicles. METHODS: The authors used vital statistics, medical examiner,
      Department of Public Safety, and Department of Transportation records to identify
      snowmobile injury deaths, and used vital statistics mortality files to identify
      on-road motor vehicle injury deaths. The Alaska Trauma Registry provided data on
      hospitalizations. The number of vehicles in use in 1993-1994 was estimated from
      snowmobile sales and on-road motor vehicle registrations. RESULTS: For 1993-1994,
      injury death and hospitalization rates were greater for snowmobiles than for on
      road motor vehicles. In northern Alaska, snowmobile injuries outnumbered on-road
      motor vehicle injuries. A total of 26 snowmobile injury deaths were reported; 7
      decedents drowned after breaking through ice and 8 were ejected from vehicles.
      More than half (58%) of the snowmobile injury deaths involved a natural object
      such as a boulder, ravine, or river. Of the 17 decedents for whom blood alcohol
      concentrations were available, 11 (65%) had blood alcohol concentrations > or =
      100 mg/dL. CONCLUSIONS: Natural obstacles and alcohol intoxication contribute to
      the high risk of injury death associated with snowmobile use. Injury control
      strategies, including trail development and improvement, should be evaluated.

PMID- 9925172
TI  - Farm tractor safety in Kentucky, 1995.
AB  - OBJECTIVE: Tractor rollovers are a major cause of farm injuries and fatalities.
      The authors used data from a statewide surveillance study to estimate the
      prevalence of safety features such as rollover protective structures, seat belts,
      and power take-off shields on farm tractors in Kentucky. METHODS: Using data from
      the Farm Family Health and Hazard Surveillance Project, the authors report on the
      prevalence of farm tractor safety features by size of farm, by region of the
      state, by number of tractors per farm, and by tractor age and estimate the
      prevalence of tractors equipped with rollover protection by region and for the
      state as a whole. RESULTS: Of the estimated 85,446 family-owned farms in Kentucky
      with at least one tractor, an estimated 55.6%, or 47,515 farms, do not have a
      tractor equipped with a rollover protective structure. Few tractors that are 10
      years old or older were found to be equipped with seat belts; no tractors that
      were more than 20 years old were equipped with seat belts. CONCLUSIONS: Kentucky,
      with an estimated 25 to 30 tractor-related fatalities each year, may contribute
      up to 20% of the total number of farm tractor fatalities in the nation. The
      overall prevalence of rollover protective structures on tractors in Kentucky is
      lower than estimates for other states as reported in national survey data. The
      study's findings suggest the need to target smaller farms with one or two
      tractors for retrofitting of rollover protective structures and for tractor
      safety programs.

PMID- 9925174
TI  - Using the birth certificate to monitor smoking during pregnancy.

PMID- 9925173
TI  - Evaluation of four maternal smoking questions.
AB  - OBJECTIVE: The authors evaluated four questions about maternal smoking during
      pregnancy for use on birth certificates. METHODS: Question 1 (yes/no format) and
      Question 2 (trimester-specific design) were tested among 1171 women who delivered
      at two Kaiser Permanente medical centers in northern California. Responses to
      Questions 1 and 2 were compared with smoking information provided by participants
      in telephone interviews conducted during pregnancy. Question 3 (multiple choice
      format) and Question 4 (month- and grouped month-specific design) were tested
      among 900 women who enrolled in a statewide prenatal screening program and who
      delivered in 20 hospitals in four Central Valley counties. Responses to Questions
      3 and 4 were compared with mid-pregnancy serum cotinine levels. The authors
      evaluated the four questions in terms of conciseness, response rate, data
      accuracy, and type of data requested. RESULTS: Questions 1 and 2 were the most
      concise. Response rates could not be calculated for Questions 1 and 2. Response
      rates were 86.0% for Question 3 and 74.2% for Question 4. Sensitivity was 47.3%
      for Question 1, 62.1% for Question 2, 83.8% for Question 3, and 86.7% for
      Question 4. The types of data requested by Questions 2 and 4 seem to best satisfy
      the needs of the broad audience of birth certificate users. CONCLUSIONS: No
      single question was clearly superior. The authors propose a combination of
      Questions 2 and 4, which asks about average number of cigarettes smoked per day
      in the three months before pregnancy and in each trimester of pregnancy.

PMID- 9925175
TI  - Trial marriage: Florida's experience in consolidating HIV/AIDS, STD, and TB
      programs.
AB  - After a three-year experiment in consolidating services, the Florida Department
      of Health has again separated programs for the prevention and control of
      HIV/AIDS, sexually transmitted diseases (STDs), and tuberculosis. The authors
      report that while there were some clear advantages to consolidating services,
      especially programs dealing with HIV and other STDs, the individual programs
      suffered in some important ways. The authors describe Florida's effort to
      preserve the positive programmatic and administrative aspects of the consolidated
      approach and to apply the lessons learned.

PMID- 9925176
TI  - Hoarding of animals: an under-recognized public health problem in a difficult-to
      study population.
AB  - OBJECTIVE: The objective of this study was to better characterize the problem of
      hoarding, or pathological collecting, of animals. METHODS: The author summarized
      data from a convenience sample of 54 case reports from 10 animal control agencies
      and humane societies across the country. RESULTS: The majority (76%) of hoarders
      were female, and 46% were 60 years of age or older. About half of the hoarders
      lived in single-person households. The animals most frequently involved were
      cats, dogs, farm animals, and birds. The median number of animals per case was
      39, but there were four cases of more than 100 animals in a household. In 80% of
      cases animals were reportedly found dead or in poor condition. Prevalence
      estimates extrapolated from these data range from 700 to 2000 U.S. cases
      annually. CONCLUSIONS: Public health authorities should recognize that animal
      hoarding may be a sentinel for mental health problems or dementia, which merit
      serious assessment and prompt intervention. Improved cooperation between humane
      societies and public health authorities could facilitate the resolution of animal
      hoarding cases.

PMID- 9925177
TI  - Reproductive health in South Africa.

PMID- 9925178
TI  - An algorithm to match registries with minimal disclosure of individual
      identities.

PMID- 9925180
TI  - Growth hormone response to growth hormone-releasing hormone stimulation in
      obsessive-compulsive disorder.
AB  - Two groups of 30 patients with obsessive-compulsive disorder and 30 age- and sex
      matched healthy control subjects were given a growth hormone-releasing hormone
      (GHRH) stimulation test to determine: (1) whether the downstream function of the
      somatotropic axis (growth hormone = GH, somatomedin-C = SMD-C) was impaired; (2)
      what might be the central alteration responsible for such impairment; and (3)
      whether alterations might be linked to the etiopathogenesis of the disease. Basal
      values of GH and SMD-C were the same in patients and control subjects, but GH
      responses to GHRH stimulation were significantly lower in patients than in
      control subjects. The absence of a pathology of basal GH and SMD-C concentrations
      indicates that the blunted GH responses to GHRH stimulation are not due to a
      negative feedback mechanism and suggests that a central neurotransmitter
      neuropeptide pathology might be involved in the phenomenon.

PMID- 9925179
TI  - Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes
      excluded in generalized social phobia.
AB  - Social phobia, particularly the generalized form, is strongly familial and
      frequently comorbid with major depression, panic disorder, and obsessive
      compulsive disorder. It has also recently been shown to be responsive to
      selective serotonin reuptake inhibitors. We conducted a study to determine if
      generalized social phobia is genetically linked to either of two candidate genes:
      the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR)
      gene. Rates of social phobia (using several phenotype definitions) were
      ascertained and blood samples obtained from consenting first-degree family
      members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was
      performed using the polymerase chain reaction (PCR). Linkage was tested using
      LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis
      indicated that failure to find linkage was unlikely due to inadequate statistical
      power. These findings reasonably exclude linkage between generalized social
      phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects
      cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects
      of 5HT on other neurotransmitter systems may be involved.

PMID- 9925181
TI  - Dissociation of affect recognition and mood state from blunting in patients with
      schizophrenia.
AB  - The present study was designed to investigate the relationships between
      expression, perception, and experience of emotion in schizophrenic patients with
      and without affective blunting. Cognitive processing speed, emotional perception,
      and emotional experience were assessed in 25 schizophrenic patients grouped
      according to scores on a measure of overt emotional expression (Rating Scale for
      Emotional Blunting). Results showed dissociation of emotional expression from
      emotional perception and emotional experience. Blunted schizophrenic patients
      were no more impaired in the perception of emotion (Profile of Nonverbal
      Sensitivity) than non-blunted schizophrenic patients. In addition, groups did not
      differ in intensity of emotional experience as quantified on the self-report of
      arousal state (Positive and Negative Affect Scales). Accuracy of perception and
      reported experience of emotion did not differ between groups as a function of
      emotional valence. Cognitive processing speed (Symbol Digit Modalities Test;
      SDMT) was related to blunting score and to perception accuracy, although the SDMT
      did not differ between groups. Results are discussed in terms of a
      neuropathological basis for impairment of emotional expression.

PMID- 9925182
TI  - Divided attention in major depression.
AB  - Depressive illness has been reported to interfere with effortful processing,
      which requires conscious attention. The aim of this study was to evaluate divided
      attention in depressed patients, as a function of the degree of difficulty of the
      task performed. Tasks designed to measure unimodal and bimodal reaction times
      were presented to 10 patients with major depression and 10 normal control
      subjects. Performance was evaluated both before treatment when the patients were
      depressed and after treatment when they had recovered. Unlike the unimodal
      trials, the bimodal reaction time tasks were designed to evaluate decision-making
      under conditions in which attention was divided between two perceptual channels.
      Reaction times were measured under two different conditions in order to assess
      the extent of the response delay induced by divided attention, modality shifting,
      and decision processing. During simple response tasks, the depressed patients
      displayed significantly greater lengthening of reaction times when their
      attention was divided between two perceptual channels. This cross-modal delay
      effect occurred both for stimuli of the same modality and when shifting between
      modalities. The cross-modal delay effect was evident only for the choice tests in
      both the depressed and the recovered patients, but only the recovered patients
      were as accurate as the control subjects. These results suggest that the need for
      decision processing in depressed patients results in a failure to allocate the
      mental resources required to complete interchannel shifting, when attention is
      divided between two perceptual channels. These data are consistent with the
      hypothesis that attentional regulation is impaired in major depression.

PMID- 9925183
TI  - Effects of specific dopamine D1 and D2 receptor antagonists and agonists and
      neuroleptic drugs on emotional defecation in a rat model of akathisia.
AB  - An increase in emotional defecation in rats in a well-habituated environment
      induced by neuroleptic drugs (NDef) has been proposed as a model for neuroleptic
      induced akathisia. We examined the effects of dopamine receptor antagonists and
      agonists on this model. A selective dopamine D1 antagonist (SCH 23390) and a
      selective D2 antagonist (raclopride) induced increased defecation at higher
      doses, and demonstrated a synergistic effect at lower doses. Selective D1 (SKF
      82958) and D2 (quinpirole) agonists did not have a significant effect on
      defecation, nor did they reverse the effect of haloperidol. In a further pilot
      study, we explored the effects of typical and atypical neuroleptics on this
      model. The haloperidol and risperidone treated rats produced more faecal boli
      than those treated with clozapine, thioridazine and chlorpromazine, with the
      former being non-significantly greater than the vehicle-treated group. The
      results of our studies suggest that NDef is most probably an effect of central
      dopamine antagonism that is not specific to D1 or D2 receptors, but that the two
      receptor subtypes have a synergistic effect. It is unlikely to be due to actions
      of neuroleptics on 5HT2 or alpha1 receptors as has sometimes been suggested. The
      results have implications for our understanding of the pathogenesis of akathisia.

PMID- 9925184
TI  - An investigation of ethnic and gender differences in the pharmacodynamics of
      haloperidol.
AB  - The objective of this study was to examine neuroleptic effectiveness among Asians
      and Caucasians, and to investigate inter-ethnic pharmacodynamic differences.
      Asians and Caucasians suffering a first episode of psychosis were maintained on
      low oral doses of haloperidol (2 mg/day) for the first week of treatment. Doses
      were increased weekly until the optimal therapeutic dosage was achieved. This was
      defined as the point at which subjects: (a) experienced significant clinical
      improvement; or (b) developed extrapyramidal side effects. Plasma haloperidol and
      prolactin were measured at intake, at the end of first week of the treatment on
      haloperidol 2 mg/day, and at optimal therapeutic dosage. The average optimal
      dosage for Asians and Caucasians was equal. However, at the end of the first week
      of haloperidol at a fixed dose of 2 mg, Caucasian males had significantly lower
      plasma haloperidol levels than Asian males while no ethnic differences in
      haloperidol levels were found among females. There were no ethnicity or gender
      effects on plasma prolactin response after 1 week of treatment. Ethnicity and
      gender may affect haloperidol metabolism.

PMID- 9925185
TI  - Prevalence of symptoms of depression in a nationwide sample of Korean adults.
AB  - The prevalence and correlates of symptoms of depression in a nationwide sample of
      Korean adults, collected during the National Health and Health Behavior
      Examination Survey, were examined. A probability sample of 3,711 respondents (a
      response rate of 81.3%) completed the Center for Epidemiologic Studies Depression
      Scale (CES-D) and a variety of sociodemographic questions. In this sample 23.1%
      of males and 27.4% of females had scores above the cutoff point of 16 (probable
      depression) on the CES-D scale, and 6.8% of males and 10.4% of females were above
      the cutoff point of 25 (severe, definite depression). Apart from a few reports
      describing Afro-American and Puerto-Rican samples, these rates were somewhat
      higher than those found in the US and Western countries. In this report, female
      gender, fewer than 13 years of education, and disrupted marriage
      (widowed/divorced/separated) proved to be statistically significant predictors of
      severe, definite symptoms of depression.

PMID- 9925186
TI  - Childhood parental loss and schizophrenia: evidence against pathogenic but for
      some pathoplastic effects.
AB  - Childhood parental loss has been associated with a number of psychiatric
      disorders in adulthood. The present article aims to examine, firstly, the
      etiologic relationship between early parental loss and later development of
      schizophrenia and, secondly, the pathoplastic effect of the former on the
      symptomatology of the latter. We have administered semi-structured interviews
      inquiring into psychopathology and early separation experiences to a
      representative sample of first-visit patients to the 31 hospitals and clinics all
      over Japan (n=1963) and also to a community sample in a small city in Japan
      (n=218). When 225 patients diagnosed with schizophrenia according to DSM-III-R
      criteria were compared with 122 healthy control subjects without any lifetime
      psychiatric disorder, controlled for sex and age, there was no statistically
      significant difference in the rates of childhood parental loss (death or
      separation). As regards the pathoplastic effects, it was found that schizophrenic
      men were less likely to present with negative symptoms if they had experienced
      separation from the father, and were more likely to show panic attacks if they
      had experienced separation from the mother. Schizophrenic women were more likely
      to present with hallucinations if they had suffered any loss of the father.
      Childhood parental loss is not pathogenic of schizophrenia but appears to exert
      some pathoplastic influences on its presenting symptoms.

PMID- 9925187
TI  - Peripheral-type benzodiazepine receptors in diagnostic subtypes of schizophrenic
      patients.
AB  - The peripheral-type benzodiazepine receptor (pBZD-R; also called the omega-3
      receptor or the mitochondrial benzodiazepine receptor) seems to play a critical
      role in the production of neurosteroids, which are able to alter the electrical
      properties of neuronal membranes and thus the firing patterns of neurons.
      Putative endogenous ligands are the diazepam-binding inhibitor and its processing
      products, as well as porphyrins, some of them, in the case of porphyria, are well
      known to give rise to certain aspects of neuropsychiatric disorders, such as
      schizophrenic-like symptoms. Previous findings of altered benzodiazepine binding
      sites in post-mortem brain samples and platelets from small samples of
      schizophrenic patients have been inconclusive. Therefore we investigated
      characteristic binding parameters (Bmax, Kd) of the granulocytic pBZD-R by using
      the selective ligand PK11.195 in 53 subjects, fulfilling ICD-10 and DSM-IV
      criteria of schizophrenia. The binding parameters in our total group of 53
      schizophrenic patients did not differ from those in healthy subjects. However,
      Bmax values were significantly reduced in schizophrenic patients with
      predominantly negative symptoms (residual type) compared to schizophrenic
      patients with predominantly positive symptoms, i.e. paranoid (-50%) and catatonic
      subtype (-38%). Moreover, only residual type schizophrenics exhibited a
      significantly reduced binding capacity compared to healthy subjects (-38%). More
      studies are warranted to clarify the functional significance of this binding site
      in the pathogenesis of negative symptoms.

PMID- 9925188
TI  - Serologic survey of adult patients with obsessive-compulsive disorder for neuron
      specific and other autoantibodies.
AB  - A subset of patients with pediatric onset obsessive-compulsive disorder (OCD) and
      tic syndromes (e.g. Tourette's syndrome) have symptom onset or exacerbation
      associated with infection. Some of these patients have been demonstrated to have
      antineuronal antibodies reactive with nuclei of the basal ganglion. It has been
      hypothesized that these patients have an immune process initiated by infection
      that affects the basal ganglion and causes obsessive-compulsive symptoms. The
      term pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS) has been coined to describe those patients with
      evidence of recent group A beta hemolytic streptococcal infection. We tested the
      serum from 13 adult patients with obsessive-compulsive disorder for panels of
      autoantibodies that serve as markers of autoimmunity in the practice of neurology
      and internal medicine. We investigated the frequency of neuron-specific
      autoantibodies [N-type and P/Q-type voltage-gated calcium channel antibodies,
      type 1 Purkinje cell antibodies, types 1 and 2 antineuronal nuclear antibodies,
      amphiphysin antibodies, and glutamic acid decarboxylase (65 kDa) antibodies],
      other organ-specific autoantibodies (muscle acetylcholine receptor-binding
      antibodies, striated muscle antibodies, thyroid microsomal and thyroglobulin
      antibodies), and non-organ-specific autoantibodies (antinuclear antibodies,
      antimitochondrial antibodies, and smooth muscle antibodies) to determine if any
      of these antibodies might serve as a serological marker for adult OCD or yield
      evidence of an autoimmune diathesis. Although most of our subjects had onset of
      OCD before 19 years of age (N=8) or before puberty (N=4), the study revealed no
      humoral evidence of autoimmunity involving the neuron-, organ-, and non-organ
      specific antibodies that we assayed.

PMID- 9925190
TI  - Direct assessment of improvement in winter depression with a visual analogue
      scale: high reliability and validity.
AB  - Reliability and validity of direct visual analogue scale (VAS) ratings of
      improvement were assessed in 162 patients with Seasonal Affective Disorder,
      Winter Depression type (W-SAD), after light treatment for 6 consecutive days. The
      patients were rated with the Montgomery-Asberg Depression Rating Scale (MADRS)
      and a scale for the 'atypical' symptoms hypersomnia, hyperphagia and carbohydrate
      craving (the ATYP scale) before and after treatment. After treatment the patients
      also self-rated their global improvement on a 10-cm VAS, with anchoring points of
      'No improvement' and 'Complete improvement'. VAS ratings were repeated several
      times, with 1-4 weeks between assessments, in a follow-up period, always
      referring to improvement in relation to baseline, and accompanied by a statement
      whether there had been any change since the former VAS rating. Shortly after
      treatment there was a mean reduction of 59.8% on the MADRS and 57.1% on the ATYP
      score, and 58.4% improvement as measured by the VAS. VAS rating correlated highly
      with percentage reduction of MADRS scores (r=0.85) and somewhat less with
      reduction of ATYP scores (r=0.64). VAS ratings in the follow-up period showed an
      extremely high test-retest reliability (r=0.96) for two consecutive ratings
      between which the patient stated that there had been no definite change. The
      results support the use of VAS ratings for assessment of global improvement after
      light treatment in patients suffering from W-SAD; use in other kinds of
      depression and with other types of treatment remains to be explored.

PMID- 9925189
TI  - Relationship between SCL-90, Maudsley Personality Inventory and CCK4-induced
      intracellular calcium response in T cells.
AB  - This study examined the relationship between the Symptom Checklist 90 (SCL-90),
      Maudsley Personality Inventory (MPI) and cholecystokinin 4 (CCK4)-induced
      intracellular calcium response in T cells. Fifty-two normal volunteers were 37
      males and 15 females; they ranged in age from 23 to 44 years. Measures included
      CCK4-induced intracellular calcium response in T cells, SCL-90 scores, and MPI.
      Paranoid ideation and interpersonal sensitivity in SCL-90 showed a significant
      negative association with CCK4-induced intracellular calcium response. Absent
      were sex differences and extroversion and neuroticism correlations. There were no
      significant differences between men and women in SCL-90 or MPI scores. There was
      no correlation among extroversion and neuroticism and CCK4-induced intracellular
      calcium response. CCKB receptor function might play a role in paranoid ideation
      and interpersonal sensitivity.

PMID- 9925191
TI  - Diagnostic subgrouping of depressed patients by principal component analysis and
      visualized pattern recognition.
AB  - A data-analytical method is described for identifying behavioral and biological
      variables in psychiatric patients with predictive value in defining clinical
      subgroups. The procedure, based on principal component analysis (PCA) and
      graphical analysis, was applied in a group of 28 depressed patients. The 28
      depressed patients of unipolar type were observed for up to 15 years for re
      evaluation of the diagnoses at the start of the study. Platelet monoamine oxidase
      activity, post-dexamethasone serum cortisol and serum melatonin predicted two
      main clinical subgroups as well as a smaller subgroup of bipolar patients. The
      selection procedure revealed which of several variables were predictive of
      subgroups that were not possible to identify by univariate methods. The three
      biological variables may thus be useful in further assessment of clinical
      subgroups of unipolar depressed patients studied by other research groups.

PMID- 9925192
TI  - Relationships between low red blood cell count and clinical response to
      fluoxetine in depressed elderly patients.
AB  - Biological variables specifically linked with serotonin deficiency were assessed
      in geriatric depression. Sixteen depressed patients, all > or = 60 years of age
      and with scores on the Montgomery-Asberg Depression Rating Scale (MADRS) > or =
      20, were treated with fluoxetine (20 mg/day) for 42 days. Biological variables
      measured on days 1 and 42 included whole blood and plasma serotonin, plasma total
      and free tryptophan, and platelet paroxetine and ketanserin binding. Seven of the
      16 patients showed a positive clinical response (i.e. MADRS score < or = 12 at
      day 42). The pre-treatment red blood cell count was the variable most related to
      clinical response; low levels were found in almost all responders. To a lesser
      extent, plasma free tryptophan before treatment was also correlated to
      therapeutic response, with lower values being found in responders. During
      treatment, plasma free tryptophan was increased in responders and decreased in
      non-responders. The finding that elderly depressed patients with low pre
      treatment red blood cell counts subsequently responded to fluoxetine treatment is
      consistent with the view that tryptophan, the precursor of serotonin in brain, is
      taken up by red blood cells.

PMID- 9925193
TI  - Practice expense.

PMID- 9925194
TI  - Total knee arthroplasty in Paget's disease: technical problems and results.
AB  - Eleven total knee arthroplasties performed in 10 patients with Paget's disease
      were reviewed at 2 to 16 years postoperatively. Cemented total knee
      arthroplasties were performed in all cases. Range of motion improved by 21
      degrees postoperatively and the follow-up Knee Society score averaged 83 points.
      One knee was rated poor with a score <70 points; this knee was the only knee with
      a loose component. All components resting on pagetic bone had a solid interface
      on radiographic review at an average of 5.7 years postoperatively. Although
      technical difficulties are encountered in achieving correct alignment and
      exposing the knee with local Paget's disease, good long-term outcome can be
      achieved.

PMID- 9925195
TI  - Hip fracture in the elderly: the effect of anesthetic technique.
AB  - Seven hundred forty-nine community-dwelling, previously ambulatory, elderly
      patients who sustained a femoral neck or intertrochanteric fracture underwent
      prospective follow-up to determine whether anesthetic technique (spinal or
      general) had an effect on inpatient morbidity and mortality, or 1-year mortality.
      One hundred seven patients were excluded from the study as the anesthetic
      technique was "predetermined" based on a underlying medical condition. Of the
      remaining 642 patients, 362 (56.4%) received general and 280 (43.6%) received
      spinal anesthesia. Twenty (3.1%) patients died during hospitalization; 73 (11.4%)
      patients developed one or more postoperative medical complications. The 1-year
      mortality rate was 12.1%. There was no difference in inpatient morbidity and
      mortality, or 1-year mortality rates between patients receiving general or spinal
      anesthesia.

PMID- 9925196
TI  - Cementless coated and noncoated Mathys acetabular cups: radiographic and
      histologic evaluation.
AB  - This study evaluated 185 cementless Mathys coated and uncoated acetabular cups
      inserted for total hip replacement since September 1984. All of the cups were
      high-density polyethylene. Sixty were uncoated (group A), 96 were coated with
      hydroxyapatite (group B), and 29 were coated with titanium (group C). Cup
      survival was assessed clinically, histologically, and radiographically, and a
      computer-assisted EBRA method was used to evaluate cup migration. After a mean
      follow-up of 8 years, five cups in group A that had previously shown migration
      were revised as a result of aseptic loosening, while no loosening of hip sockets
      occurred in groups B and C. These results suggest that Mathys cups should be used
      only if coated with hydroxyapatite or titanium. Furthermore, the histologic
      evaluation in four cups from groups B and C revealed normal bone formation
      without inflammation or fibrotic tissue around the cups, promising long-term
      survival.

PMID- 9925197
TI  - Pediatric vertebral and spinal cord tumors: a retrospective study of
      musculoskeletal aspects of presentation, treatment, and complications.
AB  - Fifty-two pediatric patients with documented vertebral and spinal cord tumors
      were reviewed to evaluate the musculoskeletal manifestations of presentation,
      treatment, and management of complications. Diagnoses included 16 malignant and
      36 nonmalignant vertebral and spinal cord tumors. Mean age at diagnosis was 8
      years 1 month, and the male-to-female ratio was 1.7:1. Overall, there was an
      average delay in diagnosis of 12 months for this group of patients. Mean clinical
      follow-up was 5 years. The two most common reasons for presentation were pain
      (67%) and spinal deformity (46%). Initial plain radiographs were positive in 82%
      of patients. Postlaminectomy spinal deformity occurred at a rate of 45% in
      patients undergoing laminectomies, and 60% of those with deformity required
      spinal fusion. Overall, 67% of the 52 patients underwent spinal fusion, with a 9%
      asymptomatic pseudarthrosis rate. Complications were common, with 1.9
      complications per patient; 59% of complications required surgical management.
      There were no perioperative deaths. At follow-up, 19% of patients had neurologic
      deficits ranging from neurogenic bladder to lower extremity weakness and
      difficulty walking to quadriplegic. Eighty-six percent of patients were
      ambulating without difficulty at follow-up. The survival rate was 94% and the
      local recurrence rate was 27% at most recent follow-up.

PMID- 9925198
TI  - Tensile force in limb lengthening: histogenesis or only mechanical elongation.
AB  - Although bone response can be evaluated by radiography, there have been no
      reports in human confirming formation of new soft tissue in limb lengthening.
      This study evaluated the tensile force between pin clamps in 14 lower limb
      lengthenings. Legs were lengthened 0.5 mm every 12 hours and the tensile was
      measured continuously. The tensile force increased simultaneously with each
      lengthening and decreased gradually. However, the reduction rate of tensile force
      during the nighttime (120+/-22%) was significantly higher than that during the
      daytime (72+/-10%). This differed from the stress relaxation phenomenon shown by
      viscoelastic material and suggested the presence of other phenomena such as
      histogenesis.

PMID- 9925199
TI  - MRI description of vertebral osteomyelitis, neoplasm, and compression fracture.

PMID- 9925200
TI  - Calcium pyrophosphate deposition disease mimicking infection in the lumbar spine.

PMID- 9925201
TI  - Malignant lymphoma at the site of a total hip replacement.

PMID- 9925202
TI  - Biplane osteotomy and epiphysiodesis of the distal radius for correction of wrist
      deformity due to distal ulnar growth arrest.

PMID- 9925203
TI  - Radiologic case study. Rapidly progressive neuroarthropathy secondary to diabetes
      mellitus.

PMID- 9925204
TI  - E. P. Pope Memorial Award to Dr. John J. Andrews.

PMID- 9925205
TI  - Reproduction of lesions of postweaning multisystemic wasting syndrome in
      gnotobiotic piglets.
AB  - Neonatal gnotobiotic piglets were inoculated with tissue homogenates and low- and
      high-passage cell culture material to determine if the lesions of the newly
      described porcine postweaning multisystemic wasting syndrome (PMWS) could be
      reproduced. For this, 17 3-day-old gnotobiotic piglets were inoculated
      intranasally with pelleted chloroform-treated, filtered extracts from cell
      cultures, filter-sterilized homogenates of lymphoid tissue from PMWS-affected
      piglets, or control materials. Piglets were maintained in germ-free isolators for
      up to 5 weeks after infection prior to euthanasia and collection of samples for
      analysis. All piglets inoculated with the viral inocula developed lesions typical
      of PMWS, including generalized lymphadenopathy, hepatitis, nephritis,
      interstitial pneumonia, myocarditis, and gastritis. Porcine circovirus (PCV), as
      well as porcine parvovirus (PPV), was detected in tissues by virus reisolation,
      polymerase chain reaction analysis, or immunohistochemistry. All infected piglets
      developed moderate to high titers of antibody to PCV and moderate titers to PPV.
      No lesions, virus, or virus-specific antibodies were detected in sham-inoculated
      or uninoculated control piglets. These studies demonstrate that the lesions of
      PMWS can be experimentally reproduced in gnotobiotic piglets using filterable
      viral agents derived from pigs with PMWS and provide an experimental basis for
      further investigation into the pathogenesis and control of this emerging
      infectious disease in swine.

PMID- 9925206
TI  - Sensitivity comparison for detection of respiratory bovine coronaviruses in nasal
      samples from feedlot cattle by ELISA and isolation with the G clone of HRT-18
      cells.
AB  - A monoclonal antibody-based capture enzyme-linked immunosorbent assay (ELISA) was
      developed to detect respiratory bovine coronavirus (RBCV) antigens in nasal swabs
      collected from cattle showing signs of respiratory tract disease following
      shipping. These samples had been previously tested for RBCV by inoculation of G
      clone cultures of human rectal tumor cells (HRT-18G) and for bovine herpes virus
      1, parainfluenza virus 3, bovine adenovirus, bovine respiratory syncytial virus,
      and bovine viral diarrhea virus on other specifically permissive cell cultures.
      RBCV has not previously been recognized as an important etiological factor in the
      bovine respiratory disease complex of feedlot cattle. Thirty of 100 samples
      tested positive for RBCV antigen by capture ELISA in contrast to 38 of 100
      samples that yielded RBCV isolates in G clone cells. Samples yielding other
      bovine respiratory viruses in the absence of RBCV were negative in the capture
      ELISA, which was based on the use of a single monoclonal antibody that recognizes
      one RBCV epitope on the S glycoprotein with the broadest reactivity with
      different strains of RBCV tested. Some RBCV strains may not be detected by this
      ELISA, which may account for the higher percentage of RBCV-infected cattle
      detected by RBCV isolation. However, the ELISA was simple to perform, sensitive,
      and specific and was more rapid than virus isolation. This assay will be useful
      for processing large numbers of field samples in future epidemiologic and
      diagnostic studies of RBCV infections of cattle.

PMID- 9925207
TI  - Seroneutralization of porcine reproductive and respiratory syndrome virus
      correlates with antibody response to the GP5 major envelope glycoprotein.
AB  - To determine the structural protein of the porcine reproductive and respiratory
      syndrome virus (PRRSV) involved in the production of neutralizing antibodies
      following clinical infection, correlation was studied between virus
      neutralization capability of convalescent pig sera and antibody response to the
      open reading frames (ORFs) 3-, 4-, 5-, and 7-encoded proteins GP3, GP4, GP5, and
      N, respectively. Individual virus genes were cloned into the pGEX-4T-1 vector,
      and the recombinant viral proteins were expressed in Escherichia coli fused to
      the glutathione S-transferase (GST) protein. The resulting GST-ORF3, GST-ORF4,
      GST-ORF5, and GST-ORF7 recombinant fusion proteins were purified by
      electroelution and used as antigens for serologic testing by indirect enzyme
      linked immunosorbent assay and western immunoblotting. The overall antibody (IgG
      and IgM) titers to PRRSV of pooled convalescent pig sera were first determined by
      indirect immunofluorescence, and then sera with specific IgG titers > 1:1,024
      were tested for their specific virus neutralization activity and reactivity to
      individual recombinant fusion proteins. Except for the early immune response (as
      revealed by the presence of specific IgM), neutralizing titers were correlated
      with anti-GP5 titers but not with anti-GP3 and anti-GP4 titers. The correlation
      between virus neutralization and anti-GP5 titers was significant (r = 0.811, P <
      or = 0.001).

PMID- 9925208
TI  - Detection of porcine reproductive and respiratory syndrome virus by reverse
      transcription-polymerase chain reaction using different regions of the viral
      genome.
AB  - Serologic studies have revealed strain variability between American and European
      isolates and among American isolates of porcine reproductive and respiratory
      syndrome virus (PRRSV). The objective of this study was to develop an assay for
      the routine diagnosis of PRRSV in field specimens using reverse transcription
      polymerase chain reaction (RT-PCR) amplification of conserved genomic regions.
      Twenty-four field isolates of PRRSV from different regions of the USA were
      analyzed in the study. Six primer pairs from open reading frames (ORFs) 4, 6, and
      7 of the American strain (ATCC VR-2332) and from ORF 1b of the Lelystad strain
      were used for the amplification of the viral genome by PCR. Amplification
      products of the expected sizes were obtained from all isolates by PCR
      amplification of ORF 7, the gene encoding the nucleocapsid protein.
      Oligonucleotide primers designed to amplify ORFs 4 and 6 detected 92% and 96% of
      the isolates, respectively, whereas primers for the amplification of ORF 1b
      detected 88% of all isolates. The specificity of the amplified products of ORF 7
      from 7 field isolates and 2 reference strains was confirmed by chemiluminescent
      hybridization using an internal digoxigenin-labeled DNA probe. Sequence analysis
      of this region indicated variation in the nucleotide sequence of 2 isolates that
      did not hybridize with the internal probe. These results indicate that ORF 7 may
      serve as a potential target for the detection of PRRSV strains by RT-PCR and that
      genomic variability should be considered when nucleic acid hybridization is used
      to confirm the specificity of PCR amplification for diagnostic purposes.

PMID- 9925209
TI  - Differential serologic response to Mycoplasma ovipneumoniae and Mycoplasma
      arginini in lambs affected with chronic respiratory disease.
AB  - An enzyme-linked immunoabsorbent assay (ELISA) was used to evaluate the levels of
      antibodies to Mycoplasma ovipneumoniae and M. arginini in lambs with chronic
      respiratory disease. Sera were obtained from lambs in several flocks at various
      stages of the clinical disease and tested with sodium dodecyl sulfate (SDS)
      treated M. ovipneumoniae and M. arginini whole cells and a crude capsular extract
      of M. ovipneumoniae as the antigens. There were low levels of antibody to M.
      ovipneumoniae in flocks sampled at the early stages of infection, whereas
      increased levels of antibody were present in lambs from flocks that had
      apparently recovered from the clinical disease. Slowly rising titers of
      circulating antibodies to M. ovipneumoniae were confirmed by sequential bleeding
      of lambs during the course of the clinical disease. However, antibody levels of
      M. arginini were more likely to increase earlier in the disease process. There
      was significant cross-reactivity between the 2 SDS-treated antigens in both the
      ELISA test and western immunoblotting. In contrast, the crude capsular extract
      was specific for detecting antibodies to M. ovipneumoniae.

PMID- 9925210
TI  - An IgG avidity ELISA to discriminate between recent and chronic Neospora caninum
      infection.
AB  - The avidity of IgG antibodies directed to Neospora caninum was measured using an
      IgG avidity enzyme-linked immunosorbent assay (ELISA) employing N. caninum
      proteins incorporated into immunostimulating complexes as antigen. In this ELISA,
      low-affinity antibodies were eluted by adding an incubation step with urea after
      the serum incubation. The antibody titers obtained with and without incubation
      with urea were then used to calculate the IgG avidity values. Analysis of
      sequential sera collected from experimentally infected calves revealed that the
      avidity increased during the course of infection. Three weeks after infection,
      the IgG avidity was 9-18%, and 24 weeks later it had increased to 58-76%. Cattle
      naturally infected for more than 6 months all had avidities >50%. The results in
      this study, however preliminary, indicate that the IgG avidity ELISA can be used
      to discriminate between recent and chronic N. caninum infections and may
      therefore be a valuable complement to IgG assays in epidemiologic studies of N.
      caninum infection in cattle.

PMID- 9925211
TI  - Detection of Lawsonia intracellularis in swine using polymerase chain reaction
      methodology.
AB  - The polymerase chain reaction (PCR) was evaluated for its usefulness as a
      diagnostic tool to detect Lawsonia (ileal symbiont) intracellularis. Porcine ilea
      were collected from swine cases submitted to the Iowa State University Veterinary
      Diagnostic Laboratory between December 1, 1994, and June 30, 1995. Sampling was
      random, with no regard to health status. There were 621 ileum scrapings evaluated
      using the PCR technique. Thirty-five of the samples were positive, either by PCR
      or conventional diagnostic methods such as histology and Warthin-Starry silver
      stain. These 35 samples were further evaluated by Warthin-Starry silver stain and
      indirect immunofluorescent antibody test (IFAT) to confirm the presence of L.
      intracellularis in the tissue sections. Of the 26 samples positive by PCR, 22
      were positive by IFAT. Sixteen of the 22 were also positive when stained with
      Warthin-Starry and evaluated microscopically for typical bacteria. Nine of the
      original samples were negative by all 3 techniques. PCR appears more sensitive
      and specific for L. intracellularis detection than Warthin-Starry stain and IFAT.
      This study provides evidence that PCR may be useful as a reference standard for
      the detection of L. intracellularis. PCR may be an appropriate monitoring tool
      for swine herds because it is a rapid procedure that could be applied to batch
      testing. Although the test is currently too laborious and expensive for routine
      diagnostic use, there may be situations in which it is justified because of the
      advantages of greater sensitivity and specificity.

PMID- 9925212
TI  - Clostridium difficile: a survey of fecal carriage in cats in a veterinary medical
      teaching hospital.
AB  - Fecal samples collected from 245 cats over a 6-month period were analyzed for the
      presence of Clostridium difficile. After culture on selective media, isolates
      were identified by a latex agglutination test, and the presence of toxin A and
      toxin B gene sequences was determined by polymerase chain reaction. Clostridium
      difficile was isolated from 23 (9.4%) of the cats, and 34.8% of that group were
      colonized with toxigenic strains. All of the cats colonized with toxigenic C.
      difficile had > or = 1 of the risk factors (antibiotic use, antineoplastic
      therapy, immunosuppressive virus infection) associated with C. difficile
      infection in humans. Clostridium difficile was not found in any of the cats from
      a clinically healthy outpatient group of cats examined from the same hospital nor
      in cats from a specific-pathogen-free research colony on the same campus tested
      during the same time period. The data obtained in this study confirm the presence
      of C. difficile in cats at a veterinary teaching hospital. DNA fingerprinting
      analysis of these isolates allowed separation of the strains into 5 groups. Type
      4 strain found in 7 cats was also recovered from the floor drain in the same
      hospital, suggesting a possible source of infection. Whether the organism is of
      clinical significance in diarrheal diseases of cats remains to be determined.

PMID- 9925213
TI  - Evaluation of C3H/HeJ mice for xenodiagnosis of infection with Ehrlichia
      chaffeensis.
AB  - Because mice are experimentally susceptible to infection with Ehrlichia species,
      C3H/HeJ mice were evaluated as a potential xenodiagnostic model for detection of
      infection with and isolation of E. chaffeensis. Intraperitoneal inoculation of
      mice with E. chaffeensis-infected DH82 cell cultures produced seroconversion,
      with peak serum antibody titers of 1:256, at high dosages (>1.9 x 10(4) infected
      cells) but not at low dosages (1.9 or 1.9 x 10(2) infected cells). Ehrlichia
      chaffeensis was not reisolated from blood samples collected from inoculated mice
      on postinoculation day 21. Nested polymerase chain reaction (PCR), using primers
      specific for E. chaffeensis, was positive for only 2/70 (2.9%) tissue samples. A
      field evaluation in which C3H/HeJ mice were inoculated with blood and lymph node
      suspensions from 5 seropositive white-tailed deer, including 3 deer that were PCR
      positive for E. chaffeensis, failed to produce seroconversion in mice. The lack
      of seroconversion at low dosages, the failure to reisolate at any dosage, and the
      inability to confirm infection in PCR-positive field samples suggests C3H/HeJ
      mice are not a sensitive model for xenodiagnosis or detection of E. chaffeensis.

PMID- 9925214
TI  - Evaluation of low sodium:potassium ratios in dogs.
AB  - The results of general chemistry profiles of canine patients from Angell Memorial
      Animal Hospital, Boston, Massachusetts, during 1993 were reviewed for low (<24)
      serum sodium:potassium (Na:K) ratios. Thirty-seven dogs had low Na:K ratios. The
      medical records for 34 these patients were available and sufficiently complete to
      identify conditions that were associated with low Na:K ratios. Of these 34 dogs,
      8 (24%) had hypoadrenocorticism, and 14 had renal disease. Twenty-two of the 34
      (65%) had Na:K ratios between 24 and 20. Of these 22 dogs, 9 (41%) had renal or
      urinary tract disease, and 2 (9%) had hypoadrenocorticism. Other diagnoses in
      this group included pancreatic disease (3), disseminated neoplasia (3),
      circulatory disturbance (2), pyometra (1), mushroom poisoning (1), and behavior
      problem (1). Eight of 34 dogs had Na:K ratios between 19.9 and 15. Of these 8
      dogs, 4 (50%) had urinary tract disease, 2 had hypoadrenocorticism, 1 had
      pancreatic disease, and 1 had severe anemia and hypoproteinemia due to severe
      parasitism. All of the 4 dogs with Na:K ratios <15 had hypoadrenocorticism, and 1
      of these 4 had concurrent renal failure. In all dogs, serum potassium
      concentration was above the laboratory's reference range, but sodium was below
      the laboratory's reference range in only 18 dogs (53%). Two of the 8 (25%) dogs
      with hypoadrenocorticism had serum sodium concentrations within the laboratory's
      reference range. In this population, low Na:K ratios were invariably associated
      with hyperkalemia but not always with hyponatremia. Although numerous conditions
      were associated with a low Na:K ratio, renal disease was the most common.
      Hypoadrenocorticism was present in only 13% of dogs with Na:K ratios between 24
      and 15 but was present in all dogs with Na:K ratios <15.

PMID- 9925215
TI  - The prevalence of Cryptosporidium and Giardia spp. in fecal samples from free
      ranging white-tailed deer (Odocoileus virginianus) in the southeastern United
      States.
AB  - The prevalence of Cryptosporidium sp. and Giardia sp. in fecal samples collected
      from free-ranging white-tailed deer (Odocoileus virginianus) was determined for
      animals in Virginia and Mississippi. The 34 Virginia samples came from young of
      the year (< or =6 months of age) presented to the Wildlife Center of Virginia,
      and the 360 Mississippi samples came from animals (> or =6 months of age)
      collected from 42 different sites across the state. Cryptosporidial oocysts were
      detected in 8.8% and 5.0% and Giardia sp. cysts were detected in 2.9% and 1.1% of
      the samples from Virginia and Mississippi, respectively. Analysis of data by
      collection site was not possible because of the small number of samples from some
      sites. Therefore, collection sites in Mississippi were grouped by the stream
      basin in which they occurred. Binary logistic regression analysis indicated the
      probability of infection with Cryptosporidium sp. decreased with increasing age
      of animal in all positive stream basins except 1, in which the pattern was
      reversed. This is the first report of either Cryptosporidium sp. or Giardia sp.
      in free-ranging white-tailed deer. The role of white-tailed deer in the
      epidemiology of these parasites is unknown. However, this study demonstrates that
      white-tailed deer shed cysts and oocysts of both parasites in the environment and
      must be considered potential sources of contamination.

PMID- 9925216
TI  - Intrapericardial neoplasia in dogs.
AB  - A retrospective study was conducted from 1,919 necropsies of dogs, and 52 cases
      were selected on the basis of primary or metastatic neoplasia in the pericardium,
      the heart base, or the myocardium. Primary intrapericardial neoplasms were more
      frequent than intrapericardial metastases. Hemangiosarcomas were the most
      frequent primary neoplasms, followed by chemodectomas. Lymphomas were the most
      frequent metastatic neoplasms, followed by fibrosarcomas and rhabdomyosarcomas.
      Other neoplasms, either primary or metastatic, occurred rarely.

PMID- 9925217
TI  - Toxicosis in cattle from concurrent feeding of monensin and dried distiller's
      grains contaminated with macrolide antibiotics.
AB  - Consumption of monensin-containing feed contaminated with macrolide antibiotic
      residues resulted in the death of cattle from multiple feedlots in south-central
      Kansas. Cattle were fed milo dried distiller's grains (DDG) with solubles from a
      common source in conjunction with the ionophore antibiotic, monensin. Deaths
      occurred as early as 72-96 hours after feeding and were preceded by either no
      premonitory signs or 1 or more of the following: anorexia, depression, dyspnea,
      locomotor deficits, and recumbency. Significant gross lesions were pulmonary and
      mesenteric edema, hepatomegaly, and generalized myocardial and skeletal muscle
      pallor that was confirmed histologically as acute myodegeneration and necrosis.
      Other significant histologic lesions included centrolobular hepatocellular
      necrosis, congestion, and pulmonary interstitial and alveolar edema with fibrin
      exudation. Animals that survived beyond 6 weeks had poor weight gain and
      coalescing foci of myocardial fibrosis with residual myocardial degeneration.
      Analysis of trace mineral supplements for monensin were within the manufacturer's
      label range. The DDG samples from affected feedlots had 50-1,500 ppm of
      erythromycin, clarithromycin, and related macrolide antibiotic analogues, which
      originated in the alcohol residue. In a preliminary feeding trial, cattle fed
      this contaminated DDG in combination with monensin had clinical signs and died
      with gross and histologic findings comparable to those of the field cases. Even
      though rations supplemented with the contaminated DDG contained approved levels
      of monensin, the clinical and postmortem findings were consistent with those
      expected for monensin toxicosis. The presence of macrolide antibiotic residues in
      the contaminated feed appeared to affect the biotransformation of otherwise
      nontoxic levels of monensin, leading to clinical ionophore toxicosis.

PMID- 9925219
TI  - Predictive values of fetal histopathology and immunoperoxidase staining in
      diagnosing bovine abortion caused by Neospora caninum in a dairy herd.

PMID- 9925218
TI  - Diagnostic investigations of toxoplasmosis in four swine herds.

PMID- 9925220
TI  - Optimizing the diagnostic use of a small clinical biopsy.

PMID- 9925221
TI  - Evaluation of a commercial system for the identification of Ornithobacterium
      rhinotracheale.

PMID- 9925222
TI  - Evaluation of the hemagglutination-inhibition assay using a baculovirus-expressed
      hemagglutinin-neuraminidase protein for detection of Newcastle disease virus
      antibodies.

PMID- 9925223
TI  - Diagnosis of canine babesiosis by Percoll gradient separation of parasitized
      erythrocytes.

PMID- 9925224
TI  - A vision of health care and informatics in 2008.
AB  - By the year 2008, a major reorganization of health care services in the United
      States will have evolved from the solo- and group-practice models of the 1940s,
      with fee-for-service and insurer-indemnification financing and paper-based
      information systems, to nationwide managed care plans employing enhanced computer
      based information systems.

PMID- 9925226
TI  - Applications of telemedicine and telecommunications to disaster medicine:
      historical and future perspectives.
AB  - Disaster management utilizes diverse technologies to accomplish a complex set of
      tasks. Despite a decade of experience, few published reports have reviewed
      application of telemedicine (clinical care at a distance enabled by
      telecommunication) in disaster situations. Appropriate new telemedicine
      applications can improve future disaster medicine outcomes, based on lessons
      learned from a decade of civilian and military disaster (wide-area) telemedicine
      deployments. This manuscript reviews the history of telemedicine activities in
      actual disasters and similar scenarios as well as ongoing telemedicine
      innovations that may be applicable to disaster situations. Emergency care
      providers must begin to plan effectively to utilize disaster-specific
      telemedicine applications to improve future outcomes.

PMID- 9925227
TI  - An ethnographic, controlled study of the use of a computer-based histology atlas
      during a laboratory course.
AB  - OBJECTIVE: To evaluate the use and effect of a computer-based histology atlas
      during required laboratory sessions in a medical school histology course. DESIGN:
      Ethnographic observation of students' interactions in a factorial, controlled
      setting. MEASUREMENTS: Ethnographer's observations; student and instructor self
      report survey after each laboratory session with items rated from 1 (least) to 7
      (best); microscope practicum scores at the end of the course. RESULTS: Between
      groups assigned the atlas and those not, the ethnographer found qualitative
      differences in the semantic categories used by students in communicating with
      each other and with the faculty. Differences were also found in the quality of
      the interactions and in the learning styles used with and without the computer
      present in the laboratory. The most interactive learning style was achieved when
      a pair of students shared a computer and a microscope. Practicum grades did not
      change with respect to historical controls. Students assigned the atlas, compared
      with those not assigned, reported higher overall satisfaction (a difference in
      score of 0.1, P = 0.003) and perceived their fellow students to be more helpful
      (a difference of 0.11, P = 0.035). They rated the usefulness of the microscope
      lower (a difference of 0.23, P<0.001). CONCLUSION: A computer-based histology
      atlas induces qualitative changes in the histology laboratory environment. Most
      students and faculty reacted positively. The authors did not measure the impact
      on learning, but they found that there are aspects of using the atlas that
      instructors must manipulate to make learning optimal. Ethnographic techniques can
      be helpful in delineating the context and defining what the interventions might
      be.

PMID- 9925228
TI  - Attitudes of first-year medical students toward the confidentiality of
      computerized patient records.
AB  - OBJECTIVES: To investigate the attitudes of students entering medical school
      toward the confidentiality of computerized medical records. DESIGN: First-year
      medical students at the Vanderbilt University School of Medicine responded to a
      series of questions about a hypothetic breach of patient's privacy through a
      computerized patient record system. MEASUREMENTS: The individual authors
      independently grouped the blinded responses according to whether they were
      consistent with then-current institutional policy. These preliminary groupings
      were discussed, and final categorizations were made by consensus. RESULTS: While
      most students had a sense of what was right and wrong in absolute terms, half the
      class suggested at least one course of action that was deemed to be inconsistent
      with institutional policies. CONCLUSIONS: The authors believe that medical
      schools should directly address ethical and legal issues related to the use of
      computers in clinical practice as an integral part of medical school curricula.
      Several teaching approaches can facilitate a greater awareness of the issues
      surrounding technology and medicine.

PMID- 9925229
TI  - Image acquisition context: procedure description attributes for clinically
      relevant indexing and selective retrieval of biomedical images.
AB  - OBJECTIVE: To support clinically relevant indexing of biomedical images and image
      related information based on the attributes of image acquisition procedures and
      the judgments (observations) expressed by observers in the process of image
      interpretation. DESIGN: The authors introduce the notion of "image acquisition
      context," the set of attributes that describe image acquisition procedures, and
      present a standards-based strategy for utilizing the attributes of image
      acquisition context as indexing and retrieval keys for digital image libraries.
      METHODS: The authors' indexing strategy is based on an interdependent
      message/terminology architecture that combines the Digital Imaging and
      Communication in Medicine (DICOM) standard, the SNOMED (Systematized Nomenclature
      of Human and Veterinary Medicine) vocabulary, and the SNOMED DICOM microglossary.
      The SNOMED DICOM microglossary provides context-dependent mapping of terminology
      to DICOM data elements. RESULTS: The capability of embedding standard coded
      descriptors in DICOM image headers and image-interpretation reports improves the
      potential for selective retrieval of image-related information. This favorably
      affects information management in digital libraries.

PMID- 9925230
TI  - Representing information in patient reports using natural language processing and
      the extensible markup language.
AB  - OBJECTIVE: To design a document model that provides reliable and efficient access
      to clinical information in patient reports for a broad range of clinical
      applications, and to implement an automated method using natural language
      processing that maps textual reports to a form consistent with the model.
      METHODS: A document model that encodes structured clinical information in patient
      reports while retaining the original contents was designed using the extensible
      markup language (XML), and a document type definition (DTD) was created. An
      existing natural language processor (NLP) was modified to generate output
      consistent with the model. Two hundred reports were processed using the modified
      NLP system, and the XML output that was generated was validated using an XML
      validating parser. RESULTS: The modified NLP system successfully processed all
      200 reports. The output of one report was invalid, and 199 reports were valid XML
      forms consistent with the DTD. CONCLUSIONS: Natural language processing can be
      used to automatically create an enriched document that contains a structured
      component whose elements are linked to portions of the original textual report.
      This integrated document model provides a representation where documents
      containing specific information can be accurately and efficiently retrieved by
      querying the structured components. If manual review of the documents is desired,
      the salient information in the original reports can also be identified and
      highlighted. Using an XML model of tagging provides an additional benefit in that
      software tools that manipulate XML documents are readily available.

PMID- 9925231
TI  - The challenge to health informatics for 1999-2000: form creative partnerships
      with industry and chief information officers to enable people to use information
      to improve health.

PMID- 9925232
TI  - Gabapentin add-on treatment: how many patients become seizure-free? An open-label
      multicenter study.
AB  - The aim of the study was to find out the percentage of patients with localization
      related epilepsy achieving complete seizure control with gabapentin (GBP) add-on
      therapy. Patients under anti-epileptic drug monotherapy during 8 weeks baseline
      (BSL) with 6 or more seizures were treated with GBP for 26 weeks up to 2400
      mg/day. Patients obtaining complete seizure control of all seizures or any
      partial seizure type during the last 8 weeks were calculated. Seizure frequency
      was compared between BSL and last 8 weeks. In all, 110 patients were enrolled (92
      completed, 18 discontinued): mean age of the completers: 37.6 years (range 16
      72), median seizure frequency per 28 days at BSL: 6.8 (2.5-24.5), mean duration
      of epilepsy: 17.6 years (0.2-51.4), mean duration with GBP for completers: 182.8
      days (144-187). Complete seizure control of all seizures was achieved in 8.7% of
      patients (simple partial seizures: 13.3%, complex partial seizures 24.3%,
      secondarily generalized seizures: 61.5%): 38% of the patients became seizure-free
      in at least 1 seizure-type; 40% experienced adverse events. Assessment for
      quality of life (QoL) and trough plasma levels of GBP did not correlate with the
      good effect of GBP.

PMID- 9925233
TI  - Surgical treatment of epilepsy--clinical, radiological and histopathological
      findings in 139 children and adults.
AB  - The present study relates clinical and radiological data to histopathological
      diagnoses in the first 139 patients (children and adults) in the Goteborg
      Epilepsy Surgery series. Temporal lobe resections were most common (54.0%)
      followed by frontal lobe (18.0%) and multilobar resections (11.5%). All
      histopathological specimens were re-evaluated in connection with this study.
      Parenchymal malformations and atrophic-gliotic lesions were the most common
      histopathological findings. Microdysgenesis was more common than major
      malformations (24.5% versus 11.5%). When the MRI scans were blindly re-evaluated
      the MRI findings correlated with histopathological diagnosis in all of the
      vascular malformations, in 77.8% of the tumours, in 76.5% of the cases with
      hippocampal sclerosis but only in 28.6% of the major cortical development
      malformations. Hemispherectomies carried the best seizure outcome prognosis
      followed by temporal lobe resections (75.0% versus 57.3% seizure free 2 years
      after surgery). Vascular malformations carried the best, and microdysgenesis the
      worst prognosis (76.9% versus 39.4% seizure free).

PMID- 9925225
TI  - The basis for using the Internet to support the information needs of primary
      care.
AB  - Synthesizing the state of the art from the published literature, this review
      assesses the basis for employing the Internet to support the information needs of
      primary care. The authors survey what has been published about the information
      needs of clinical practice, including primary care, and discuss currently
      available information resources potentially relevant to primary care. Potential
      methods of linking information needs with appropriate information resources are
      described in the context of previous classifications of clinical information
      needs. Also described is the role that existing terminology mapping systems, such
      as the National Library of Medicine's Unified Medical Language System, may play
      in representing and linking information needs to answers.

PMID- 9925234
TI  - Large scale screening of the mitochondrial DNA reveals no pathogenic mutations
      but a haplotype associated with multiple sclerosis in Caucasians.
AB  - We report the first large-scale screening of mitochondrial (mt) DNA in 77
      Caucasian patients with relapsing-remitting or secondary progressive form of
      multiple sclerosis (MS) and in 84 Caucasian controls by using the method of
      restriction site polymorphism and haplotype analysis. No pathogenic mtDNA
      mutation was found in association with MS. However, mtDNA haplotypes K* and J*
      defined by the simultaneous presence of Ddel restriction sites at nucleotides
      10,394 and 14,798 of the mtDNA in haplogroups K and J showed association with MS
      at a P-value of 0.001. A relative increase of MS patients compared to controls
      either with the J* or with the K* haplotype (+10,394Ddel/+14,798Ddel in
      haplogroup J or K) also was detected (each with a P<0.05). No distinct phenotypic
      characteristics of MS were observed when clinical data of patients with
      haplotypes K* or J* were analyzed. In addition to previous complete sequencing in
      several MS patients, the population screening of mtDNA presented here suggests
      that mtDNA point mutations are not likely to be involved in the pathogenesis of
      typical forms of MS. However, the mitochondrial genetic background (haplotype K*
      and J*) may moderately contribute to MS susceptibility. The reported association
      between MS and Leber's hereditary optic nerve atrophy, a disease caused by mtDNA
      point mutations preferentially occurring in haplogroup J, may be at least in part
      related to the overlapping mitochondrial genetic background of the two diseases.

PMID- 9925235
TI  - Parkinsonism: siblings share Helicobacter pylori seropositivity and facets of
      syndrome.
AB  - OBJECTIVE: Given a history of peptic ulcer is more frequent in parkinsonism, to
      investigate the role of Helicobacter pylori in its pathogenesis and of cross
      infection in familial aggregation. METHODS: Facets of parkinsonism were
      quantified in 33 elderly subjects with idiopathic parkinsonism and in their 39
      siblings with double the number of controls, all obeying inclusion/exclusion
      criteria. Specific-IgG antibody was assayed. RESULTS: Siblings, compared with
      controls, had brady/hypokinesia of gait (P< or =0.002), bradykinesia of hands (P
      = 0.01), abnormal posture (P = 0.001), rigidity (P < 0.001) and
      seborrhoea/seborrhoeic dermatitis (P = 0.02). Both parkinsonians and siblings
      differed from controls in the odds of being H. pylori seropositive [odds ratios
      3.04 (95% C.I.: 1.22, 7.63) and 2.94 (1.26, 6.86) respectively, P < 0.02],
      seropositivity being found in 0.70 of sufferers. CONCLUSION: Familial
      transmission of chronic infection plus part of syndrome links Helicobacter with
      causality. Seropositivity not being universal throughout parkinsonism, consequent
      on gastric atrophy +/- sporadic antibiotic exposure, might explain less
      aggressive disease in older sufferers.

PMID- 9925237
TI  - Clinical features and genetic analysis of a Spanish family with spinocerebellar
      ataxia 6.
AB  - OBJECTIVE: To present the clinical features and DNA analysis of a Spanish SCA6
      family. MATERIAL AND METHODS: Four symptomatic members of the family (mean age at
      onset: 53.75+/-5.21) were examined. SCA6 CAG trinucleotide repeat was analysed in
      the proband by the polymerase chain reaction (PCR). RESULTS: Early dysphagia,
      ophthalmoparesis and neck dystonia in the oldest patient, without the loss of
      vibratory and proprioceptive sensation supporting the theory of phenotypic
      variability within families with SCA6. Our results are in accordance with the
      theory that the size of the repeat pattern correlates with the age at onset of
      the symptoms. Analysis of the SCA6 CAG trinucleotide repeat at the CACNA1A gene
      in the patient's DNA demonstrated an expanded allele of 22 CAG repeat units.
      CONCLUSIONS: This study identifies phenotypic differences in the surviving
      kindred. The diagnosis of SCA6 in family members or single affected patients can
      be made by direct molecular analysis. This makes predictive testing possible.

PMID- 9925236
TI  - Alpha-dihydroergocryptine in Parkinson's disease: a multicentre randomized double
      blind parallel group study.
AB  - INTRODUCTION: A multicentre randomized double-blind parallel group study was
      carried out on 68 patients suffering from idiopathic Parkinson's disease (PD)
      treated with L-dopa for at least 1 year with inadequate therapeutic
      responsiveness. The aim of the study was to compare the efficacy of alpha
      dihydroergocryptine (alpha-DHEC) vs lisuride as an adjunct therapy to L-dopa on
      dyskinesias and clinical fluctuations (Unified Parkinson's Disease Rating Scale
      [UPDRS] part IV), on the symptoms pattern (Columbia University Rating Scale
      [CURS]), on disability (Northwestern University Disability Scale [NUDS]), and to
      evaluate the incidence of adverse events. PATIENTS AND METHODS: Thirty-two
      patients (18 males, 14 females with a mean age of 64.5+/-1.5 SEM) were randomized
      to alpha-dihydroergocryptine and 36 (16 males, 20 females with a mean age of
      61.8+/-1.4) to lisuride. The treatment lasted 3 months and the dosage was
      increased until it reached 60 mg/day of alpha-dihydroergocryptine and 1.2 mg/day
      of lisuride, while the L-dopa dosage was kept constant in both groups. Per
      protocol and intention to treat analyses were performed on response variables.
      RESULTS: The adjunctive treatment with the two dopamine agonists determined a
      significant improvement of PD symptoms in both groups. Alpha-dihydroergocryptine
      showed a superior efficacy in reducing the clinical complications (P < 0.01 by
      ANOVA). The number of patients complaining of adverse events was 8 out of 32
      (25%) for alpha-dihydroergocryptine and 24/36 (67%) for lisuride (P < 0.05).
      CONCLUSION: Alpha-dihydroergocryptine effect seems to be superior to that of
      lisuride both in terms of reduction of L-dopa therapy long term motor
      complications (UPDRS part IV) as well as in terms of the incidence and severity
      of adverse events.

PMID- 9925238
TI  - Postural control and lifetime alcohol consumption in alcohol-dependent patients.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between alcohol
      consumption and postural control in alcohol-dependent patients. MATERIAL AND
      METHODS: Posturographic measurements were performed in 82 abstinent patients and
      in 54 healthy controls. The findings in the patients were compared with those in
      the controls as well as with the daily alcohol consumption, the consumption
      during 6 months before the admission for alcohol withdrawal therapy and the
      estimated lifetime alcohol consumption. RESULTS: Postural control was impaired in
      alcohol-dependent patients compared to healthy controls. This impairment was
      related with the lifetime alcohol consumption, but not with the alcohol
      consumption per day and prior to admission, respectively. Comparing healthy
      controls, and alcohol-dependent patients with an estimated lifetime alcohol
      consumption of < 1000 kg and > or = 1000 kg revealed a significant increase in 6
      of 8 sway parameters. Furthermore, the lifetime alcohol consumption increased
      significantly from patients with normal posturographic and clinical findings to
      those with abnormalities in both examinations. CONCLUSION: This study suggests
      that postural imbalance in abstinent alcohol-dependent patients is related to the
      lifetime alcohol consumption.

PMID- 9925239
TI  - Second European Stroke Prevention Study: antiplatelet therapy is effective
      regardless of age. ESPS2 Working Group.
AB  - BACKGROUND: The Second European Stroke Prevention Study (ESPS2) was a randomized,
      placebo-controlled trial that investigated the efficacy of low-dose
      acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in
      combination, in the secondary prevention of ischemic stroke. The trial
      demonstrated that the combination was significantly more effective than either
      agent used alone. The aim of the present study was to evaluate the influence of
      age on the efficacy of ASA and DP, alone or in combination, in the secondary
      prevention of stroke in the ESPS2 population. METHODS AND RESULTS: A total of
      6602 patients were recruited to the ESPS2 and there were 4 treatment groups: ASA
      (25 mg twice daily), DP (200 mg twice daily), ASA and DP in a combined
      formulation, or placebo. Primary endpoints were stroke, death, and stroke or
      death together. The endpoints evaluated in the present study were stroke, stroke
      and/or death, and vascular events. Stroke was the qualifying event in 76% of the
      patients, while 24% had a transient ischaemic attack. Patients were reviewed at 3
      month intervals for 2 years. The study population consisted of 2565 (39%)
      patients aged less than 65 years, 2240 (34%) patients aged between 65 and 74
      years, and 1797 (27%) patients aged 75 years and over. Advancing age was
      associated with an increased incidence of endpoints in all 4 treatment groups.
      The combination of ASA and DP significantly reduced the incidence of all
      endpoints, compared with placebo, in each age group. There was no influence of
      age on the efficacy of antiplatelet therapy for any of the evaluated endpoints.
      Relative risk reductions of treatment compared with placebo were 11.1-27.6% in
      the ASA group, 8.0-18.7% in the DP group, and 20.3-45.2% in patients receiving
      combination therapy. CONCLUSION: This study clearly demonstrates that combination
      therapy with DP and ASA is superior to either agent used alone in the secondary
      prevention of ischemic stroke, irrespective of the age of the patient.

PMID- 9925240
TI  - Interrater reliability of plaque morphology classification in patients with
      severe carotid artery stenosis.
AB  - OBJECTIVE: Ultrasonographic assessment of carotid artery plaque morphology is
      widely used to identify patients at high risk for stroke. However, the
      reliability of plaque analysis in high-grade stenosis is uncertain. We determined
      the interrater reliability of sonographic plaque morphology analysis in patients
      with severe carotid artery stenosis. MATERIALS AND METHODS: Duplex Doppler was
      performed on 114 patients with 80-99% stenosis of the internal carotid artery
      using a Siemens Quantum 2000 D with a handheld 7.5 MHz transducer. B-mode
      pictures with and without color coding were printed on a Sony color video printer
      UP-5000 W. Three raters independently evaluated plaque echolucency,
      heterogeneity, calcification, and surface structure. Interrater agreement was
      calculated by a jackknife procedure generating kappa values and two-sided 95%
      confidence intervals. RESULTS: Kappa values and 95% confidence intervals were
      0.05 (-0.07 to 0.16) for plaque surface structure, 0.15 (0.02 to 0.28) for plaque
      heterogeneity, 0.18 (0.09 to 0.29) for plaque echogenicity, and 0.29 (0.19 to
      0.39) for plaque calcification. The upper bounds of all of the confidence
      intervals were below the 0.40 level suggested for minimal reliability.
      CONCLUSION: The low interrater agreement indicated that unaided visual assessment
      of static B-mode pictures to assess plaque morphology in patients with severe
      carotid artery stenosis is not reliable. Other evaluation procedures and
      standardized criteria, as yet undeveloped, are needed to improve reliability.

PMID- 9925241
TI  - TCD, MRA and MRI in acute cerebral ischemia.
AB  - OBJECTIVES: The aim of this study was to determine accuracy of transcranial
      Doppler ultrasound (TCD) and compare efficacy of three non-invasive tests [TCD,
      magnetic resonance angiography (MRA), and magnetic resonance imaging (MRI)] in
      patients with acute cerebral ischemia. MATERIAL AND METHODS: This prospective
      study involved 30 patients. MRI, MRA, and TCD were performed within 24 h after
      onset of ictus. The 2nd MRI was repeated at 48-72 h and was used as the standard
      for the evaluation of sensitivity and specificity of MRA, TCD, and initial MRI.
      RESULTS: TCD showed a sensitivity of 96% and a specificity of 33% for recognizing
      abnormal cerebral blood flow velocities. MRA showed a sensitivity of 46% and a
      specificity of 75% for assessing intracranial vascular anatomy, while initial MRI
      revealed a sensitivity of 84% and a specificity of 100% for evaluation of
      ischemic parenchymal changes. CONCLUSION: Our results revealed that TCD is an
      accurate indicator of blood flow status and correlated well with MRI, MRA
      abnormalities in acute stroke.

PMID- 9925242
TI  - Right parietal infarction with concomitant mutism.
AB  - Right brain damage results in a variety of cognitive and behavioural
      dysfunctions. Mutism however, has been described only with left or bihemispheric
      lesions involving the parietal lobe. We report an elderly man who had left
      faciobrachial monoparesis and concomitant mutism. His auditory-verbal
      comprehension was intact. MRI revealed a right parietal infarct involving the
      cortical and subcortical regions. Recovery from mutism during the course of
      treatment was abrupt and complete with no residual dysarthria. A possibility of
      diaschisis or impaired modulation of left hemispheric function due to right
      cerebral infarct, presenting as conversion reaction, is proposed for this rare
      association.

PMID- 9925243
TI  - What does photodynamic therapy have to offer radiation oncologists (or their
      cancer patients)?
AB  - Major advances have recently been made in photodynamic therapy (PDT) for clinical
      application, including the development of more powerful photosensitizers and
      light sources and suitable light applicators. PDT is emerging as an attractive
      new form of cancer therapy, suitable for treating superficial lesions (less than
      1 cm in depth) and carcinoma in situ, or as an adjuvant to surgery for more bulky
      disease. PDT is therefore complementary to radiotherapy which is better suited to
      treating larger tumours. There are some qualitative similarities between light
      distribution in tissue during superficial illumination and ionizing radiation
      dose distributions during external beam irradiation, or between interstitial PDT
      and brachytherapy, although the geometric scale is very different (visible light
      penetrates a maximum of 5-10 mm in tissue). The contribution of scattered light
      to tissue irradiance is much greater than for ionizing radiation and in situ
      light dosimetry is very important (although rather complicated) to ensure
      adequate illumination without over-treating. Dosimetry and treatment planning are
      highly advanced for ionizing radiation and are routine in all radiotherapy
      departments. Proper in situ light dosimetry and dose distribution calculation for
      PDT is in its infancy. Physicists have an important role to play in the further
      optimization of clinical PDT and much of the infrastructure and expertise present
      in the radiotherapy department is ideally suited to accommodate PDT. In this
      review, parallels and contrasts are made between PDT and ionizing radiation for
      both mechanistic and dosimetric aspects of the therapies. A summary of the most
      interesting clinical applications is also given.

PMID- 9925244
TI  - Indications and treatment schedules for irradiation of benign diseases: a survey.
AB  - BACKGROUND: The interest in the treatment of benign diseases with radiotherapy
      has grown particularly in the Western part of the world. Questions about the
      effectiveness and risks of radiotherapy for these disorders have to be answered
      in the light of new information from clinical research, dose calculations and
      risk estimates. New indications for irradiation of non-malignant diseases, e.g.
      vascular disorders, such as macular degeneration and prevention of stent
      restenosis, are appearing. As a starting point for further discussions and
      publications in this area, the authors, with the help of the European Society for
      Therapeutic Radiology and Oncology (ESTRO), performed a survey of current
      practice and of opinion amongst ESTRO members. METHODS: A questionnaire was
      circulated in 1996 to 1348 institutes listed in the 1995 ESTRO directory asking
      whether the respondents considered a list of the 28 most common benign disorders
      as being a good indication for radiotherapy. Details of the frequency of such
      treatments and of treatment schedules used were requested. RESULTS AND
      CONCLUSIONS: A large variation in indications and treatment schedules was
      detected throughout the world. This variation confirms the inadequate information
      on which such treatments are based and stresses the importance of careful
      clinical studies and trials as well as clear understanding of any risks involved.

PMID- 9925245
TI  - Radiation-induced impairment of bone healing in the rat femur: effects of
      radiation dose, sequence and interval between surgery and irradiation.
AB  - BACKGROUND AND PURPOSE: Impairment of osseous healing in treatment combining
      surgery and radiotherapy is a frequent complication. Its dependence on sequence
      and interval was studied in a defined experimental model. MATERIALS AND METHODS:
      The effect of pre- and postoperative irradiation by single doses of X-rays on
      osseous closure of a 1.2 mm drill hole in the rat femur was measured 6 or 7 weeks
      after surgery in histological sections using morphometrical methods. RESULTS:
      Irradiation delivered between 1 day and 6 months before surgery resulted in a
      reduction of bone healing following very similar dose response relationships;
      there was no evidence of any slow repair of latent radiation damage.
      Radiosensitivity of bone healing during the first 3 days after surgery was not
      different from preoperative irradiation; however, irradiation 4 days or later
      after surgery failed to reduce osseous healing even after very high radiation
      doses. CONCLUSION: Tolerance increases enormously if radiotherapy is given later
      than 4 days after surgery. This has great implications for combined radiotherapy
      and surgery schedules involving bone reconstruction, but may be even more
      important for radiotherapy applied to prevent heterotopic ossification after
      total hip arthroplasty. Biologically, target cell regeneration alone is
      insufficient to account for the drastic rise in radiotolerance; it must be
      accompanied by an increase in cellular resistance due to differentiation.

PMID- 9925246
TI  - Fractionated total body irradiation in allogeneic bone marrow transplantation in
      leukemia patients: analysis of prognostic factors and results in 136 patients.
AB  - BACKGROUND AND PURPOSE: The results of a single-institution series of patients
      with chronic and acute leukemias are analyzed with regard to literature-reported
      predictor variables. MATERIALS AND METHODS: Between 1985 and 1994, 136 patients,
      82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL),
      received a uniform preparatory regimen of fractionated total body irradiation
      (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow
      transplantation. Eighty-six patients were considered to be in early phase of
      disease (CML in chronic phase or AL in first complete remission) and 50 in
      advanced phase (all those beyond first remission or first chronic phase). Ninety
      five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted
      BM. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of
      the whole series were 43% and 31%, and median survival was 43 and 10 months,
      respectively. A Cox proportional hazard model identified variables related to
      overall and disease-free survival. For OS, graft versus host disease (GVHD) was
      the first independent variable (P < 0.0001), followed by age (P < 0.001), T
      depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05).
      With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and
      GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were
      reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16
      patients suffered late complications. CONCLUSIONS: Our results confirm the
      curability of early phase leukemias with standard fractionated TBI-induced
      Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated
      TBI schedule as employed in our series, T-cell depletion negatively affected the
      outcome.

PMID- 9925247
TI  - Fractionated high dose rate brachytherapy moulds--a precise treatment for
      carcinoma of the pinna.
AB  - BACKGROUND AND PURPOSE: The aim of this paper is to describe a fractionated high
      dose rate brachytherapy procedure for the treatment of small superficial cancers
      of the pinna and to report the outcome in a small series of patients. MATERIALS
      AND METHODS: Thirteen patients with superficial cancers of the pinna, not
      invading cartilage, have been treated and in the majority of cases the tumour
      thickness was determined by a transdermal ultrasound measurement. For the single
      plane moulds the prescribed surface dose was 45 Gy in eight fractions over 5 days
      and the moulds were constructed such that the full thickness of the disease, as
      determined by the ultrasound measurement, would lie within the 80% isodose
      surface. One case was treated with a sandwich mould and in this case the dose was
      reduced to 42.5 Gy. The treatment machine was a high dose rate microselectron,
      which contains a single stepping iridium source. RESULTS: The radiation reactions
      were of moderate severity, but were limited to the high dose volume. In all cases
      there was complete tumour resolution and rapid healing occurred leaving a barely
      perceptible scar. There were no recurrences over a minimum follow-up time of 18
      months and there were no late radiation complications in this period.
      CONCLUSIONS: The treatment of superficial carcinoma of the pinna by means of HDR
      moulds is a safe and reliable technique. In this small series of patients there
      was total tumour control with excellent cosmesis.

PMID- 9925248
TI  - Three-dimensional dosimetry using polymer gel and magnetic resonance imaging
      applied to the verification of conformal radiation therapy in head-and-neck
      cancer.
AB  - BACKGROUND AND PURPOSE: It was our aim to investigate NMR-based BANG gel
      dosimetry as a three-dimensional dosimetry technique in conformal radiotherapy.
      MATERIALS AND METHODS: The BANG gel consisting of gelatin, water and co-monomers
      was first validated in a cylindrical glass flask for a single standard beam.
      Next, the gel contained in a human neck-shaped cast was used to verify a
      treatment plan for the conformal irradiation of a concave tumour in the lower
      neck. Magnetic resonance relaxation rate images were acquired and, based on an
      appropriate calibration of the gel, converted to absorbed dose distributions. The
      resulting maps were compared with dose distributions measured using radiographic
      film. RESULTS: The gel-measured dose profiles of standard beams agreed within 3%
      (root mean square difference) with the profiles measured with high spatial
      resolution by a diamond detector. For the multi-beam conformal treatment, the
      difference map between gel-measured and film-measured dose distributions revealed
      a noise component and a more systematic deviation including structural or space
      coherent patterns. The mean absolute value of the difference amounted to 8%. A
      number of possible causes for this deviation are designated. CONCLUSIONS: Polymer
      gel dosimetry in combination with magnetic resonance imaging is a promising
      method for dosimetric verification of conformal radiotherapy.

PMID- 9925249
TI  - Secondary neutron and photon dose in proton therapy.
AB  - BACKGROUND AND PURPOSE: The dose due to secondary neutrons and photons in proton
      therapy was estimated with Monte Carlo simulations. Three existing facilities
      treating eye and deep-seated tumours were taken into account. The results of the
      calculations related to eye proton therapy were verified with measurements.
      MATERIALS AND METHODS: The simulations were performed with the FLUKA code.
      Neutron fluence was measured inside an Alderson phantom (type ART) with
      activation techniques. RESULTS: The maximum dose due to secondaries produced in a
      passive beam delivery system was estimated to be of the order of 10(-4) and 10(
      2) Gy per therapy Gy for eye and deep tumour treatments, respectively. In the
      case of irradiations of deep-seated tumours carried out with an active system,
      the dose was of the order of 10(-3) Gy per therapy Gy. CONCLUSIONS: The dose due
      to secondaries depends on the geometry of the beam delivery system and on the
      energy of the primary beam and is lower in the healthy tissues distant from the
      target volume.

PMID- 9925250
TI  - Modulated electron beams using multi-segmented multileaf collimation.
AB  - BACKGROUND AND PURPOSE: Conformal radiation therapy by modulation of photon and
      electron beams has been described for many techniques. Modulation of electron
      beams with the use of either bolus or altered scanned beams is reported. Our
      institution previously investigated the use of MLC for fixed static electron
      fields. The results were dismal due to the wide penumbra associated with
      multileaf collimated electrons scattered from foils. The purpose of this study
      was to decipher whether multi-segmented electron beams using MLC would provide a
      useful and practical modulated beam by taking advantage of matching the diffuse
      beam edges. MATERIALS AND METHODS: We started by planning simple target shapes,
      such as wedged and parabolic shapes. We optimized the segment widths, weights,
      gaps between segments and energies. We then irradiated phantoms using film to
      confirm the calculations. The study was limited to single-plane irradiation. We
      also planned and measured isodoses for a parotid target volume that possessed
      varying depths from surface to medial aspect. RESULTS: We found that we could
      optimize distributions by using the treatment depth and points of inflection to
      derive optimal segments. The planned treatments using a simple CET (coefficient
      of equivalent thickness) algorithm were confirmed with reasonable success. A 24
      cm wide target was treated with nine segments in under 5 min, while most cases,
      including the parotid volume, were treated in under 3 min. CONCLUSIONS: We have
      developed a technique to complement a photon modulation program by treating
      lesions close to the surface. The debate as to whether this technique is optimal
      and more efficient than a bolus technique continues. We are currently devising
      methods for optimizing modulated electron MLC beams in multiple planes.

PMID- 9925251
TI  - Boron neutron capture therapy: re-irradiation response of the rat spinal cord.
AB  - PURPOSE: To evaluate the retreatment response of the CNS to BNC irradiation using
      a rat spinal cord model. MATERIALS AND METHODS: Fischer 344 rats were irradiated
      with single doses of 6 MeV X-rays which were 22, 40 or 80% of a total effect
      (TE). An additional group of rats was irradiated with a single exposure of
      thermal neutrons in the presence of the neutron capture agent boronophenylalanine
      (BPA) to a dose that represented 82% of the TE. After an interval of 26 weeks,
      animals were re-irradiated using various single doses of thermal neutrons in
      combination with BPA. RESULTS: The re-irradiation ED50 doses represented 77, 80
      or 50% of the TE after an initial X-ray dose of 22, 40 or 80% of the TE,
      respectively. The re-irradiation ED50 dose was 55% of the TE after an initial BNC
      irradiation dose representing 82% of the TE. CONCLUSION: The level of the initial
      radiation damage had a direct bearing on the re-irradiation response. Recovery
      following initial treatment with BNC irradiation was similar to that after
      initial irradiation with X-rays.

PMID- 9925252
TI  - A cone-beam megavoltage CT scanner for treatment verification in conformal
      radiotherapy.
AB  - PURPOSE: A prototype scanner for large-volume megavoltage computed tomography
      (MVCT) in a clinical set-up is described. The ultimate aim is to improve
      treatment accuracy in conformal radiotherapy through patient set-up error
      reduction and transit dosimetry. MATERIALS AND METHODS: The scanner consists of a
      custom-built 2D CsI(Tl) crystal array viewed by a lens and a CCD camera. Image
      acquisition is synchronized with radiation pulses. The 2D projections resulting
      from a single continuous 360 degrees gantry rotation are reconstructed using a
      cone-beam tomography algorithm. Prior to reconstruction, the raw projections are
      calibrated and corrected for centre of rotation movement and accelerator output
      fluctuation. The performance of the system has been evaluated by reconstructing
      projections of open fields, test objects and a humanoid phantom. RESULTS:
      Hundreds of 2D projections can be acquired with a clinically-acceptable data
      collection time (about 2 min) and dose (approximately 40 cGy, with a possible
      four-fold reduction). A maximum density resolution of about 2% is achieved
      offering some soft tissue discrimination without using image enhancement tools. A
      spatial resolution of 2.5 mm is obtained. The reconstructed image intensity is
      linear with electron density over the range of interest. Coronal or sagittal
      slices through the 3D reconstruction of the humanoid phantom show a better
      delineation of structures than the corresponding portal images taken at the same
      orientation. CONCLUSIONS: A similar image quality to our current single-slice
      MVCT scanner is achieved with the advantage of providing tens of tomographic
      slices for a single gantry rotation. This work demonstrates the feasibility of
      clinical cone-beam MVCT and indicates how this prototype can be improved.

PMID- 9925253
TI  - Paclitaxel is preferentially cytotoxic to human cervical tumor cells with low Raf
      1 kinase activity: implications for paclitaxel-based chemoradiation regimens.
AB  - BACKGROUND AND PURPOSE: Low Raf- kinase activity has been reported to be
      associated with radioresistance in epithelial tumor cell lines and with
      paclitaxel sensitivity in cervical tumor cells. Paclitaxel might thus be
      effective in eliminating radioresistant clones from cervical tumors, even in the
      absence of synergistic interaction between these therapeutic modalities. We thus
      established the relationship between Raf-1 kinase activity and radiosensitivity
      in human cervical tumor cells and determined if paclitaxel is preferentially
      cytotoxic to radio-resistant tumor clones. MATERIALS AND METHODS: We established
      and contrasted the radiation and paclitaxel sensitivity of 12 human cervical
      tumor clones that exhibited a wide range of Raf-1 kinase activity. RESULTS: Raf-1
      kinase activity was inversely correlated (P = 0.001) with SF2 values in the 12
      cervical tumor clones studied. Paclitaxel was preferentially cytotoxic to
      radioresistant tumor clones, with the level of paclitaxel-induced cytotoxicity
      being significantly (P = 0.0016) influenced by Raf-1 kinase activity levels.
      CONCLUSIONS: Our in vitro data indicate that there are marked, but completely
      opposite, Raf-1 kinase dependencies of radiation and paclitaxel cytotoxicity in
      cervical tumor cells. The use of combined paclitaxel and radiotherapy treatment
      may thus lead to higher local control rates for squamous cell carcinoma of the
      cervix. Circumstantially, our data suggest that the greatest therapeutic gains
      might accrue if paclitaxel was administered when there is the greatest proportion
      of tumor clones with low Raf-1 kinase activity. It may thus be desirable to use
      paclitaxel towards the end of radiotherapy treatment or post-radiotherapy as
      consolidation therapy.

PMID- 9925254
TI  - Dosimetric impact of computed tomography calibration on a commercial treatment
      planning system for external radiation therapy.
AB  - The Hounsfield units into density conversion for a commercial treatment planning
      system (TPS) is discussed. The impact of an average calibration table provided by
      the manufacturer on computed doses was investigated when a customer calibration
      could not be included in the TPS. The maximum error determined on the computed
      monitor units per Gy was found to be about 2%, being below 1% on average. The
      relative importance of the parameters used for CT image acquisition is also
      discussed. The applied voltage was the most relevant parameter leading to errors
      in the reconstructed Hounsfield numbers of about 300 units for high densities.

PMID- 9925255
TI  - Simplified non-looping functional loop technique for HDR brachytherapy.
AB  - The loop technique has been employed in interstitial implantation of head and
      neck cancers for decades. However, cable-driven afterloading sources may be
      unable to negotiate the curve of the loop. The technique allows separate
      afterloading of each catheter ensuring a good dose distribution to the surface of
      the implanted structure.

PMID- 9925256
TI  - An external marker for accurate patient positioning in radiotherapy CT scanning.

PMID- 9925257
TI  - Comment on: A randomized double-blind phase III study of nimorazole as a hypoxic
      radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx
      carcinoma. Results of the the Danish Head and Neck Cancer Study (DAHNCA) Protocol
      5-85.

PMID- 9925258
TI  - Comment on: Conservative surgery and radiotherapy in early stage breast cancer: a
      comparison between tumourectomy and quadrantectomy.

PMID- 9925259
TI  - Comment on: Tumor volume as a response predictor in radiotherapy.

PMID- 9925260
TI  - Isolation in immunodeficient mice of Sarcocystis neurona from opossum (Didelphis
      virginiana) faeces, and its differentiation from Sarcocystis falcatula.
AB  - Sarcocystis neurona was isolated in nude mice and gamma-interferon knockout mice
      fed sporocysts from faeces of naturally infected opossums (Didelphis virginiana).
      Mice fed sporocysts became lethargic and developed encephalitis. Protozoa were
      first found in the brain starting 21 days post-inoculation. Sarcocystis neurona
      was recovered in cell culture from the homogenate of liver, spleen and brain of a
      nude mouse 11 days after feeding sporocysts. The protozoa in mouse brain and in
      cell culture multiplied by schizogony and mature schizonts often had a residual
      body. Sarcocystis falcatula, which has an avian-opossum cycle, was not infective
      to nude or knockout mice. Protozoa were not found in tissues of nude mice or
      knockout mice after subcutaneous injection with culture-derived S. falcatula
      merozoites and sporocysts from the faeces of opossums presumed to contain only S.
      falcatula. Results demonstrate that S. neurona is distinct from S. falcatula, and
      that opossums are hosts for both species.

PMID- 9925261
TI  - Antigenic variation and the murine immune response to Giardia lamblia.
AB  - The protozoan parasite Giardia lamblia is an important causative agent of acute
      or chronic diarrhoea in humans and various animals. During infection, the
      parasite survives the host's reactions by undergoing continuous antigenic
      variation of its major surface antigen, named VSP (variant surface protein). The
      VSPs form a unique family of cysteine-rich proteins that are extremely
      heterogeneous in size. The relevance of antigenic variation for the survival in
      the host has been most successfully studied by performing experimental infections
      in a combined mother/offspring mouse system and by using the G. lamblia clone
      GS/M-83-H7 (human isolate) as model parasite. In-vivo antigenic variation of G.
      lamblia clone GS/M-83-H7 is characterised by a diversification of the intestinal
      parasite population into a complex mixture of different variant antigen types. It
      could be shown that maternally transferred lactogenic anti-VSP IgA antibodies
      exhibit cytotoxic activity on the Giardia variant-specific trophozoites in
      suckling mice, and thus express a modulatory function on the proliferative
      parasite population characteristics. Complementarily, in-vitro as well as in-vivo
      experiments in adult animals indicated that non-immunological factors such as
      intestinal proteases may interfere into the process of antigen variation in that
      they favour proliferation of those variant antigen-type populations which resist
      the hostile physiological conditions within the intestine. These observations
      suggest that an interplay between immunological and physiological factors, rather
      than one of these two factor alone, modulates antigenic diversification of a G.
      lamblia population within an experimental murine host and thus influences the
      survival rate and strategy of the parasite.

PMID- 9925262
TI  - Intracellular alkalinisation in Vero cells parasitised by Trypanosoma cruzi.
AB  - We studied the intracellular pH of Vero cells parasitised by Trypanosoma cruzi,
      using different methods: fluorimetric measurement after labelling the cells with
      the pH-sensitive intracellular fluorescent dye 2',7',-bis-(2-carboxyethyl)-5-(and
      6)-carboxyfluorescein, acetoxymethyl ester; flow cytometry; and image analysis
      after staining the cells with neutral-red vital stain. The results show that the
      intracellular pH of the parasitised cells rose in comparison with that of the
      uninfected control cells. A study of the population of parasitised cells made by
      flow cytometry allowed us to subdivide the cells from the infected cultures into
      two populations according to their pH as obtained by fluorimetric measurements.
      Image analysis showed that the cell cytoplasm was more alkaline in the vicinity
      of the sites containing parasites. Treatment of the parasitised cells with
      amiloride, ouabain, or with 4.4'-diisothiocyano-2,2'-stilbene disulphate
      consistently lowered the pH values of the parasitised cells, but not sufficiently
      to return to the values of the non-parasitised control cells. When the control
      cells were subject to similar treatments with the inhibitors, only amiloride
      acidified the cytoplasm to any extent. The basification undergone by the
      parasitised cells was independent of the transport systems and may be a
      consequence of the release of NH4+ by the intracellular amastigotes.

PMID- 9925263
TI  - Changes in antigen and glycoprotein patterns during the development of
      Oesophagostomum dentatum.
AB  - During its development from free-living infectious third-stage larvae to the
      adult worms in the large intestines of pigs, Oesophagostomum dentatum experiences
      several environmental changes. Differences in protein patterns can reflect such
      changes. Somatic and ES antigens and glycoproteins of pre-parasitic, histotropic
      and intestinal stages were compared by single-dimension SDS-PAGE and stage
      specific proteins were defined. Furthermore, fourth-stage larvae derived from
      different sources--in-vitro cultivation and intestinal contents--were compared
      and also found to be different. It is hypothesised that O. dentatum reacts to
      environmental stimuli by differential expression of specific proteins as a
      possible mode of adaptation to the host.

PMID- 9925264
TI  - Is there a fixed number of niches for endoparasites of fish?
AB  - Kennedy and Guegan, based on Cornell and Lawton (J Anim Ecol 1992;61:1-12), found
      a "curvilinear" relationship (the "fundamental form" of the relationship for
      parasite communities) between infracommunity and component community richness,
      and interpreted this as meaning that only processes acting within the
      infracommunities can explain the limitation in the number of parasite species in
      a given host. The research described here shows that an asymptotic relationship
      is the consequence of the differential likelihoods of parasite species to appear
      in an infracommunity as determined by transmission rates and intrinsic lifespans.
      Processes operating at the infracommunity level are not necessary to explain the
      curvilinear relationship. Even communities much richer than those found in
      European freshwater fishes cannot be assumed to be "saturated" in the sense that
      further species cannot be added over evolutionary time.

PMID- 9925265
TI  - Characterisation of Trypanosoma cruzi populations by DNA polymorphism of the
      cruzipain gene detected by single-stranded DNA conformation polymorphism (SSCP)
      and direct sequencing.
AB  - Fifty fresh isolates of Trypanosoma cruzi from Triatoma dimidiata vectors and 31
      from patients with Chagas' disease were analysed for DNA polymorphisms within the
      432-bp core region of the cruzipain gene which encodes the active site of
      cathepsin L-like cystein proteinase. The cruzipain gene showed signs of
      polymorphism consisting of four different DNA sequences in Central and South
      American isolates of T. cruzi. The PCR fragments of Guatemalan isolates could be
      divided into three groups, Groups 1, 2 and 3, based on different patterns of
      single-stranded DNA conformation polymorphism. All of the strains isolated from
      Brazil, Chile, and Paraguay, except for the CL strain, showed a Group 4 pattern.
      Two to four isolates from each group were analysed by cloning and sequencing. A
      silent mutation occurred between Groups 1 and 2, and five nucleotides and two aa
      substitutions were detected between Groups 1 and 3. The DNA sequence of Group 4
      contained five nucleotides and one aa substitution from Group 1. All of the DNA
      sequences corresponded well with the single-stranded DNA conformation
      polymorphism. The Group 1 isolates, the majority in the Guatemalan population
      (70/81, 86.4%), were isolated from both triatomines and humans, but Group 3 were
      isolated only from humans. Moreover, the Group 2 isolates were detected only in
      triatomine vectors (9/50; 18%), but never in humans (0/32, P<0.05) suggesting
      that this group has an independent life-cycle in sylvatic animals and is
      maintained by reservoir hosts other than humans.

PMID- 9925266
TI  - A Cryptosporidium parvum oocyst low molecular mass fraction evokes a CD4+ T-cell
      dependent IFN-gamma response in bovine peripheral blood mononuclear cell
      cultures.
AB  - T-Cell antigens that induce the in-vitro interferon-gamma response during
      Cryptosporidium parvum infection of neonatal calves were identified. A total
      oocyst extract was separated into a high and a low Mr fraction by a
      microfiltration technique. Both the high and low Mr fractions evoked an in-vitro
      interferon-gamma response in naturally infected animals, although strong
      individual differences between the hosts were observed. Using a complement
      mediated technique CD4+ T-cells or WC1+gammadelta T-cells were depleted,
      whereupon the remaining lymphocyte cultures were stimulated with the different
      antigen preparations. It was shown that the in-vitro interferon-gamma response of
      Cryptosporidium-infected calves is CD4+ T-cell-dependent.

PMID- 9925267
TI  - Fuchsin fluorescence and autofluorescence in Cryptosporidium, Isospora and
      Cyclospora oocysts.
AB  - Cryptosporidium parvum and Isospora belli oocysts stained with carbol-fuchsin, as
      in a modified Ziehl Neelsen technique, fluoresce bright red under green light
      (546nm). Cryptosporidium oocysts tend to fluoresce more brightly the less
      intensely stained they appear under transmitted light; this is not the case with
      Isospora. Fuchsin-stained Cyclospora cayetanensis oocysts fluoresce rather dimly,
      but those not taking the dye retain their typical autofluorescence.
      Cryptosporidium and Isospora oocysts are also autofluorescent, appearing violet
      under u.v. light (365 nm), and green under violet (405 nm) and blue-violet light
      (436 nm). Their autofluorescence does not survive the staining procedure.

PMID- 9925268
TI  - Intestinal Cryptosporidium sp. infection in the Egyptian tortoise, Testudo
      kleinmanni.
AB  - An adult Egyptian tortoise (Testudo kleinmanni) presented with clinical signs of
      enteritis and died 5 weeks after initiation of antibiotic therapy. Histological
      examination of the small intestine revealed heavy infection with Cryptosporidium
      sp.; over 80% of epithelial cells harboured the pathogen. No Cryptosporidium
      developmental stages were present in the stomach or the lungs. The intestinal
      lamina propria and mucosa were infiltrated by heterophils, lymphocytes and
      macrophages. The present study constitutes the first report of Cryptosporidium
      sp. infection in T. kleinmanni, and the first histological documentation of
      intestinal cryptosporidiosis in Chelonia.

PMID- 9925269
TI  - Eimeria species in the Pearson Island Rock Wallaby, Petrogale lateralis pearsoni.
AB  - Four species of previously described Eimeria were identified from oocysts present
      in the faeces of Pearson Island rock wallabies, Petrogale lateralis pearsoni from
      Pearson Island, South Australia. Eimeria petrogale and Eimeria sharmani have been
      reported in P. lateralis; however, the presence of Eimeria godmani and Eimeria
      inornata expands the suite of eimerian species known in rock wallabies of the
      "lateralis" complex. These observations indicate that the host distribution of
      Eimeria species in rock wallabies is more diverse than previously thought, and
      supports the hypothesis that these coccidia have an ancient association with rock
      wallabies which persisted as the hosts radiated.

PMID- 9925270
TI  - Production of monoclonal antibodies against target schistosomal antigen secreted
      in the urine of Schistosoma mansoni-infected patients.
AB  - This study was undertaken to develop an immunodiagnostic test of active human
      schistosomiasis mansoni using a monoclonal antibody which targets urinary
      schistosomal antigen. Polyclonal antisera raised in rabbits against the processed
      urine of Schistosoma mansoni-infected patients showed very high and significant
      reactivity with ES product of ova compared with other different S. mansoni
      antigens. The monoclonal antibody (4.23) was reactive with repetitive epitopes of
      S. mansoni soluble egg antigen and ES product of ova with molecular mass range of
      65-23 kDa and 80-23 kDa, respectively. It recognised different stages of the
      parasite life-cycle, with no cross reaction with Fasciola or hydatid antigen.
      MAbs were characterised by isotyping, immunoelectrophoresis, SDS-PAGE and the
      enzyme-linked immunoelectrotransfer blot technique, ELISA, and their recognition
      of carbohydrate or protein antigenic epitopes by periodate oxidation and
      trichloroacetic acid treatment of the antigen. It was used for detection of
      circulating schistosomal antigen in an antigen capture antibody sandwich ELISA on
      sera and urines of 58 S. mansoni-infected patients, 17 S. haematobium-infected
      patients, 15 parasite-free negative healthy controls and sera from 13
      schistosomiasis-free patients harbouring Fasciola or hydatid infections. The
      percentage sensitivity of the assay in the serum of S. mansoni-infected patients
      was 98.4% and in urine 94.8%. A positive correlation was found between the number
      of faecal S. mansoni eggs and the circulating antigen, both in serum and in
      urine. Antigen circulating in urine correlated with that in the sera of S.
      mansoni patients. These data provide a sensitive and non-invasive method almost
      comparable with the use of sera for immunodiagnosis of schistosomiasis and an
      indirect way to reflect the intensity of infection.

PMID- 9925271
TI  - Distinguishing Oesophagostomum dentatum from Oesophagostomum quadrispinulatum
      developmental stages by a single-strand conformation polymorphism method.
AB  - At some life-cycle stages, it is impossible to distinguish between the two
      species of porcine nodular worm, Oesophagostomum dentatum and Oesophagostomum
      quadrispinulatum, using morphological features. A PCR-based single-strand
      conformation polymorphism technique was established to overcome this limitation.
      The rDNA region spanning the second internal transcribed spacer was amplified by
      PCR from genomic DNA from morphologically well-defined adult worms. The PCR
      products were then denatured and subjected to electrophoresis in a non-denaturing
      gel matrix. Single-strand conformation polymorphism analysis of the products
      generated characteristic and reproducible patterns for each of the two species
      and allowed their unequivocal delineation. The single-strand conformation
      polymorphism was also applied effectively to assess the purity of nine laboratory
      maintained cultures of infective third-stage larvae believed to be monospecific
      for O. dentatum or O. quadrispinulatum. The analysis showed that all six O.
      dentatum cultures were indeed monospecific, whereas the three cultures believed
      to be monospecific for O. quadrispinulatum were either a mixture of O. dentatum
      and O. quadrispinulatum larvae or pure O. dentatum larvae. These findings
      demonstrated the usefulness of the single-strand conformation polymorphism
      approach for the routine monitoring of the purity of parasite "lines" and
      indicated its value for studies on the population biology of porcine nodular
      worms.

PMID- 9925272
TI  - Characterisation of anisakid nematodes with zoonotic potential by nuclear
      ribosomal DNA sequences.
AB  - Larvae of three species of anisakid nematode from fish, Anisakis simplex,
      Hysterothylacium aduncum and Contracaecum osculatum, were characterised
      genetically using a molecular approach. The nuclear ribosomal DNA region spanning
      the first internal transcribed spacer, the 5.8S gene and the second internal
      transcribed spacer was amplified and sequenced. The lengths of the first and
      second internal transcribed spacer sequences of the three species ranged from 392
      to 449 bp and 262 to 347 bp, respectively, whereas the 5.8S sequence was 157 bp.
      For the three species, the G+C contents for the three regions of ribosomal DNA
      ranged from 42.4 to 52.2%. While no intraspecific variation was detected in the
      second internal transcribed spacer or 5.8S sequence of any species examined, one
      polymorphic nucleotide position was detected in the first internal transcribed
      spacer sequence for A. simplex and H. aduncum. The extent of sequence differences
      in the first (approximately 34-45%) and second (approximately 50-53%) internal
      transcribed spacers among the species was greater than in the 5.8S gene
      (approximately 3-5%). Based on the sequence differences, PCR-based restriction
      fragment length polymorphism and single-strand conformation polymorphism methods
      were established for the unequivocal delineation of the three species. These
      methods should provide valuable tools for studying the life-cycle, transmission
      pattern(s) and population structure of each of the three anisakid nematodes
      examined herein, and for the diagnosis of anisakiasis in humans and animals.

PMID- 9925273
TI  - Sequence heterogeneity in a repetitive DNA element of Fasciola.
AB  - A repetitive DNA sequence used as a specific probe for Fasciola hepatica
      infections in snails was examined in F. hepatica and Fasciola gigantica (36
      individuals) specimens from five continents. The degree of intraspecific identity
      ranged from 79 to 99% in F. hepatica and from 93 to 99% in F. gigantica. The
      interspecific identity ranged from 81 to 100%, confirming the suggestion that the
      DNA probe sequence could be used worldwide as an epidemiological tool for the
      examination of the intermediate host snail in fasciolosis. Differentiation
      between F. hepatica and F. gigantica infections in snails was not possible using
      the probe.

PMID- 9925274
TI  - Variation in the sequence of a mitochondrial NADH dehydrogenase I gene fragment
      among six natural populations of Schistosoma japonicum from China.
AB  - The present study investigated the level of genetic variation among Schistosoma
      japonicum populations of different geographical origins from mainland China.
      Polymerase chain reaction-based methods were employed to determine the sequence
      for a subunit of the mitochondrial NADH dehydrogenase I gene for populations from
      Zhejiang, Anhui, Jiangxi, Hunan, Hubei and Sichuan. No variation was detectable
      in the NADH dehydrogenase I sequence within populations from Zhejiang and Hubei,
      whereas sequence variation of 0.2% was detected within populations from Anhui,
      Jiangxi, Hunan and Sichuan. Pairwise comparison of the sequences representing the
      six different populations revealed genetic differences ranging from 0 to 0.6%.

PMID- 9925275
TI  - Evaluation of the infectivity of Trichinella spp. for reptiles (Caiman sclerops).
AB  - Experimental inoculation with nine well-characterised Trichinella isolates was
      performed on caimans (Caiman sclerops) to determine their infectivity for
      reptiles belonging to the family Crocodilidae. As controls, the same larval
      batches of Trichinella isolates were inoculated into mice and guinea pigs. It was
      suggested that Trichinella pseudospiralis was more likely to infect reptiles than
      encapsulating species, but whereas all Trichinella species established in mice
      and guinea pigs, the caimans remained negative. The finding that caimans could
      not be experimentally infected contrasts with a recent report on infections in
      farmed crocodiles (Crocodylus niloticus).

PMID- 9925276
TI  - Most of the species on Earth are parasites.

PMID- 9925277
TI  - Does the presence of Spirometra erinacei reduce the efficacy of praziquantel
      against Echinococcus granulosus in dogs?

PMID- 9925278
TI  - Cytotoxic effect of substitution at 2-, 6-, and 2,6-positions in ascorbic acid on
      malignant cell line.
AB  - In recent years L-ascorbic acid (AA) and its isomers have raised considerable
      interest as anticancer agents, although the mechanism has remained largely
      unknown. AA isomers are nearly identical in their physical and chemical
      properties but differ widely in their biological properties. AA, a lactone sugar,
      has a number of reactive positions, especially at 2- and 6-. Although there are a
      number of reports on the cytotoxic effect of AA and its isomers on malignant and
      nonmalignant cell lines, no work has been reported on the comparative effects of
      substitutions at these active sites. This study, then, investigates the
      comparative cytotoxicity of such substitutes on the malignant leukemia P388 cell
      line in culture. We tested a series of 2-, 6- and 2,6- disubstituted AA
      derivatives, comprising the following: i) substitution at 2-position: -PO4, -SO4,
      O-Me, O-octadecyl; ii) substitution at 6-position: -PO4, -SO4, -palmitate, 
      stearate; and iii) substitution at 2,6-position: -dipalmitate. About 50,000 P388
      cells/ml were incubated with and without AA derivatives in a final concentration
      of 1000, 500, 100, 10 and 1 microg/ml in triplicate and counted after 72 hrs. All
      2-substituted and the 2,6-substituted AA derivatives tested were nontoxic and
      ineffective in preventing cell growth. In contrast, all 6-substituted AA
      derivatives were very toxic at all levels, even at the lowest concentration.
      These results suggest that substitution at 2-, 6- and 2,6-positions in AA have a
      different effect on toxicity. The 2-, and 2,6-substituted AA derivatives are
      stable compounds, resistant to hydrolysis which render them inactive. The
      cytotoxicity of the 6-substituted derivatives may be explained by one of the
      following mechanisms, yet to be explored: i) the hydrolysis rate may differ; or
      ii) the chemical structure itself may affect toxicity. Further studies are in
      progress to understand the mechanism.

PMID- 9925279
TI  - Profiles of the fatty acids in the plasma membrane of human brain tumors.
AB  - Several studies demonstrated that certain fatty acids have specific effects on
      tumor cells. n-3 series fatty acids (alpha-linolenic acid, eicosapentaenoic acid
      and docosahexaenoic acid) may suppress the carcinogenesis, whereas n-6 series
      fatty acids (arachidonic acid, linoleic acid) may exert tumor promoting effects.
      In this study, 19 patients with various brain tumors and 12 control brain tissues
      were studied. n-3, n-6, n-9 unsaturated fatty acids and certain saturated fatty
      acids levels were measured in the plasma membrane of tumor or control brain
      tissues by capillary gas chromatography. We found that the level of
      docosahexaenoic acid from n-3 series fatty acids was significantly lower in
      gliomas and meningiomas than controls (p = 0.000). Total n-3 fatty acids level
      was also significantly lower in tumors than controls (p = 0.000). The levels of
      linoleic acid, arachidonic acid and dihomogamma linolenic acid from n-6 series
      were significantly higher in gliomas and meningiomas compared with controls (p =
      0.000). Total n-6 fatty acids level was also significantly higher in tumors than
      controls (p = 0.000). Furthermore, in total n-9 fatty acids, total unsaturated
      fatty acids and total saturated fatty acids levels, there were no significant
      differences in gliomas and meningiomas compared with controls (p = 0.6840, p =
      0.4388 and p = 0.4343, respectively). This findings suggest that n-6 fatty acids
      can act as a tumor-promoting agent in human brain tumors.

PMID- 9925280
TI  - Chemical, metabolic and immunological characterization of gangliosides of human
      glioma cells.
AB  - The patterns of ganglioside profiles were studied in 10 human glioma and one
      melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1
      4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1
      1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha
      2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant
      constituents. The activities of the two key enzymes, GM3 synthetase and
      lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the
      ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl
      showed more pronounced difference in the synthetic rate of each ganglioside type,
      in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines.
      On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of
      above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the
      ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and
      A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant
      type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the
      antibody binding to these gangliosides were examined in native forms in the cell
      membrane and in chemically-isolated forms. The intensity of reaction against
      chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and
      GM2 was more reactive than GM3; however, the reactivities on the cell surface did
      not correlate with the chemical content indicating other factors to influence
      their immunoreactivities.

PMID- 9925281
TI  - Breast cancer and benign breast disease patients evaluated in relation to
      oxidative stress.
AB  - In this study, breast cancer (n = 23) and benign breast disease (n = 15) patients
      were evaluated in relation to oxidative stress. The extent of lipid peroxidation
      was assessed by measuring thiobarbituric acid reactive substances (TBARS) in
      plasma. Erythrocyte glutathione peroxidase (GSH Px), CuZn speroxide dismutase
      (CuZn SOD), glutathione (GSH) and plasma vitamin E, cholesterol Fe, Zn, Cu levels
      were analysed in both groups GSH Px (p < 0.01), vitamin E (p < 0.001), Zn (p <
      0.01), Cu (p < 0.05) and cholesterol (p < 0.01) concentrations were found to be
      significantly increased, TBARS level (p < 0.01) significantly decreased in breast
      cancer patients in comparison to benign breast disease group.

PMID- 9925282
TI  - Effects of cytoskeletal inhibitors on the accumulation of vincristine in a
      resistant human lung cancer cell line with high level of polymerized tubulin.
AB  - We have previously established a vincristine resistant human lung cancer cell
      line (PC-9/VCR) by a stepwise exposure of parental line PC-9 to vincristine. In
      this study the resistant cells showed enhanced vincristine cytotoxicity in the
      presence of cytochalasin B and D. The increase in cytotoxicity was associated
      with an enhanced accumulation and a reduced efflux of vincristine. Colchicine and
      taxol had no effects on vincristine accumulation. Several cytoplasmic proteins
      were overexpressed in the resistant cells. The two major ones, with molecular
      weights of 58.8 kDa and 83.2 kDa, were shown by western blotting to be beta
      tubulin and actin, respectively. The polymerized tubulin level in the resistant
      cells was significantly (p < 0.05) higher than that in the parental cells. These
      results suggest that the cellular cytoskeletons might play an important role in
      VCR resistance in the PC-9/VCR human lung cancer cell line.

PMID- 9925283
TI  - Native fluorescence spectroscopy of normal and malignant epithelial cells.
AB  - Native fluorescence spectroscopy of normal human oral and malignant epithelial
      cells was studied under uv excitation. Differences were observed in the
      excitation spectra between normal and malignant epithelial cells for 340 nm
      emission. The observed differences may be utilized for both discrimination and
      changes associated with the amino acid residues in the cellular proteins.

PMID- 9925284
TI  - The instability of polyhydroxylated aromatic protein tyrosine kinase inhibitors
      in the presence of manganese.
AB  - Inhibition of the tyrosine kinase activity of Src by forty-three different
      compounds from five chemical families (cinnamic acid, salicylic acid, phenol,
      coumarin and flavonoid derivatives) representing plant and microbial secondary
      metabolites were studied in the presence of MgCl2 versus MnCl2. Within each
      chemical family, compounds containing multiple hydroxyl substituents demonstrated
      the greatest inhibitor potency. The ortho-substituted dihydroxy compounds were
      the most inhibitory. Except for the flavonoids, inhibition was higher in the
      presence of manganese compared to that observed with magnesium. UV-Vis spectra,
      HPLC, and mass spectrometric analyses demonstrate that manganese catalyzed the
      oxidation of these compounds. The general instability of such compounds,
      especially in the presence of manganese, and the associated problems it causes in
      the use of such compounds for developing selective protein tyrosine kinase
      inhibitors, is discussed.

PMID- 9925285
TI  - The effects of reverse micelles on the reaction mechanism of alpha-chymotrypsin.
AB  - Reverse micelles were employed to test the accuracy of the widely accepted
      mechanism for alpha-chymotrypsin in a highly structured aqueous system similar to
      intracellular conditions. Results yielded from spectrophotometrical assays of the
      alpha-chymotrypsin catalyzed hydrolysis of both p-nitrophenyl acetate (p-NPA) and
      p-nitrophenyl trimethylacetate (p-NPTA) were kinetically analyzed to determine
      constants typical of the proposed mechanistic model. This was accomplished
      through the establishment of a control, i.e. the well studied buffer system, for
      comparison between the reverse micellular environment and a bulk aqueous
      solution. Control group results yielded kinetic constants in favor of the
      proposed mechanism (Km = 1.55 x 10(-5) +/- 1.40 x 10(-6) M for p-NPA and a Km =
      4.97 x 10(-6) +/- 2.29 x 10(-7) M, Km(app) = 4.92 x 10(-6) +/- 2.33 x 10(-8) M,
      k2 = 4.34 x 10(-3) +/- 1.31 x 10(-3), k(cat) = 1.96 x 10(-3) +/- 2.47 x 10(-4),
      and Ks = 1.60 x 10(-5) +/- 4.61 x 10(-6) M for p-NPTA). In contrast, similar
      reactions of the enzyme in a reverse micellular system produced kinetic constants
      atypical to that representative of the textbook mechanism. (Km = 1.59 x 10(-4) +/
      2.70 x 10(-5) M, Ks = -8.67 x 10(-5) +/- 4.46 x 10(-5) M and Km(app) = -4.80 x
      10(-5) +/- 7.05 x 10(-5) M for p-NPA and Km = 1.95 x 10(-4) +/- 9.28 x 10(-5) M,
      Km(app) = -1.79 x 10(-4) +/- 2.36 x 10(-5) M, and Ks = -3.95 x 10(-4) +/- 1.18 x
      10(-4) M for p-NPTA). In addition to negative kinetic constants, alpha
      chymotrypsin seemed to display characteristics indicative of super-activity and a
      hysteretic response. Overall, the widely accepted mechanism for alpha
      chymotrypsin appeared to fail within the confines of reverse micelles, due to the
      direct influence of the system's highly structured form.

PMID- 9925286
TI  - Evaluation of the cytotoxic activity of polyethers isolated from Laurencia.
AB  - In this paper, we report on the conformational analysis of several polyether
      triterpenes with a squalene carbon skeleton which exhibited significant cytotoxic
      activity using a Monte Carlo conformational search and spectroscopical data.
      These studies indicate that the conformation of the side chain C-14/C-19 and the
      arrangement and direction of this chain may be among the fundamental factors
      related to the activity of this type of metabolites.

PMID- 9925288
TI  - Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of
      substituted 3-chloro-5,8-dimethoxy-1,4-naphthoquinone and related compounds.
AB  - 2-Amino (6), 2-alkylamino (7-8), 2-methoxy (9), 2-acetamido (10), and 5,8
      diacetoxy (11) derivatives of the lead compound 2,3-dichloro-5,8-dimethoxy-1,4
      naphthoquinone (4) were synthesized, together with 6,7-dichloro-5,8dimethoxy-1,4
      naphthoquinone (5), a positional isomer of 4. Antiplatelet, antiinflammatory, and
      antiallergic activities were evaluated, and most compounds were quite potent in
      all assays. Compounds 5 and 9-11 were especially active; however, 5 was
      ineffective against neutrophil superoxide formation, and 10 was ineffective
      against mast cell degranulation.

PMID- 9925287
TI  - Ligand binding to I2 imidazoline receptor: the role of lipophilicity in
      quantitative structure-activity relationship models.
AB  - A series of 2-trans-styryl-imidazoline (tracizoline) congeners were designed and
      tested to develop 2-D and 3-D QSAR models for their binding to imidazoline (I2)
      receptor. The important role of lipophilicity was assessed by classical 2-D QSAR
      study (Hansch approach) and by comparative molecular field analysis (CoMFA) with
      the inclusion of the molecular lipophilicity potential (MLP), as an additional
      descriptor, besides standard steric and electrostatic fields. Results from these
      studies were compared to those obtained in a previous modeling study of I2
      receptor ligands and integrated into a new, comprehensive model, based on about
      sixty I2 receptor ligands. This model revealed, at the three-dimensional level,
      the most significant steric, electrostatic, and lipophilic interactions
      accounting for high I2 receptor affinity.

PMID- 9925290
TI  - Synthesis of a tetracyclic, conformationally constrained analogue of delta8-THC.
AB  - A tetracyclic, conformationally constrained analogue of delta8-THC (2) has been
      synthesized in which a two carbon bridge exists between C2 and C2'. Two
      conceptually related syntheses of 2 are described, both of which employ 5,7
      dimethoxy-4-oxo-1,2,3,4-tetrahydronaphthoic acid (11) as starting material. This
      substrate was converted to 5,7dimethoxy-2-propyl-1,2,3,4-tetrahydronaphthalene
      (7) and its 4-keto derivative (18). Demethylation of 11 and 18 provided the
      corresponding resorcinols, which were condensed with trans-p-menthadienol to
      afford cannabinoid 2, and a keto derivative (20). LiA1H4/A1C1(3) reduction of 20
      provided 2. Cannabinoid 2 has relatively low affinity for the cannabinoid brain
      receptor (Ki = 703+/-98 nM).

PMID- 9925289
TI  - Synthesis and antiviral activity of a new series of 4-isothiazolecarbonitriles.
AB  - A series of 4-isothiazolecarbonitriles was synthesized and screened for in vitro
      antiviral activity. The effect of various substituents on the phenyl ring, as
      well as the substitution of the phenyl for other aromatic and heteroaromatic
      rings, was examined to establish the requirements for optimum activity. The most
      active member of the series, 3methylthio-5-phenyl-4-isothiazolecarbonitrile,
      exhibited a high level of activity against enteroviruses polio 1 and ECHO 9.
      Preliminary studies on its mechanism of action indicated that this compound had
      an effect on an early event in the replication of poliovirus type 1.

PMID- 9925291
TI  - Synthesis, characterization, and anticonvulsant activity of enaminones. Part 5:
      investigations on 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothizin-4[10H]-one
      derivatives.
AB  - A new series of anticonvulsant 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin
      4[10H]-on es is herein reported. 2-Aminothiophenols underwent cyclocondensation
      with 4-carboalkoxy-5-methylcyclohexane-1,3-diones in refluxing dimethylsulfoxide
      (DMSO) to yield 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-on es,
      4ak. In the case of the carbo-tert-butoxy derivatives (4c and 4k) prolonged
      reaction times led to the isolation of the respective 3-unsubstituted-2-methyl
      2,3-dihydro-1H-phenothiazin-4[10H]-ones (41 and 4m) instead. Significant
      anticonvulsant activity was displayed by these analogues, most particularly 4k,
      which was active at 30 mg/kg intraperitoneally (ip) in mice in the maximal
      electroshock seizure (MES) evaluation, with no toxicity noted at dosages up to
      300 mg/kg. Oral (p.o.) rat evaluation of 4k in the MES evaluation provided an
      ED50 of 17.60 mg/kg, with no toxicity noted at dosages up to 500 mg/kg, providing
      a protective index (PI = TD50/ED50) > 28.40. These compounds represent the first
      reported series of phenothiazines which possess anticonvulsant activity.

PMID- 9925292
TI  - The discovery and structure-activity relationships of nonpeptide, low molecular
      weight antagonists selective for the endothelin ET(B) receptor.
AB  - The systematic modification of the ETA selective N-(5-isoxazolyl)benzene
      sulfonamide endothelin antagonists to give ETB selective antagonists is reported.
      The reversal in selectivity was brought about by substitution of the 4-position
      with aryl and substituted aryl groups. Of all the aromatic substituents studied,
      the para-tolyl group gave rise to the most active and selective ETB antagonist.
      Larger substituents caused a decrease in both ETB activity and selectivity. A
      similar trend was observed by substitution at the 5-position of the N-(5
      isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group
      was again found to be optimal for the ETB activity and selectivity. The
      structural features that were found to be favorable for binding to the ETB
      receptor, that is, the presence of a linear, conjugated pi-system of definite
      shape and size, have been successfully incorporated into the design of ETB
      selective polycyclic aromatic sulfonamides antagonists.

PMID- 9925293
TI  - Novel small renin inhibitors containing 4,5- or 3,5-dihydroxy-2-substituted-6
      phenylhexanamide replacements at the P2-P3 sites.
AB  - Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6
      phenylhexanamide fragment at the P2-P3 sites have been prepared and evaluated.
      The four possible diastereomeric diols of the two series of inhibitors were
      synthesized to determine the optimal configuration of the carbinol centers for
      these replacements. The most potent inhibitors of each series, la and 2c have a
      molecular weight of only 503 and IC50 values of 23 and 20 nM in a human plasma
      renin assay at pH 6.0. Their very low aqueous solubility limited their further
      evaluation. The efficacy of these P2-P3 replacements is a result of their ability
      to maintain the important hydrogen-bonds with the enzyme. Due to conformational
      differences with the dipeptide, adjustment at the P2 side chain was required.
      These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal
      dipeptide replacements.

PMID- 9925294
TI  - Structural basis for selective inhibition of COX-2 by nimesulide.
AB  - Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the
      enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1).
      Molecular modelling studies have been carried out on complexes of 1 with COX-1
      and with mutants of COX-1 simulating COX-2. These indicate that the mutations
      I523V and S516A largely contribute to the selectivity. A comparative study with
      SC-558 2 has also been performed.

PMID- 9925295
TI  - Preparation and biological activity of novel tricyclic GPIIb/IIIa antagonists.
AB  - Antagonists of the glycoprotein GPIIb/IIIa are a promising class of
      antithrombotic agents offering potential advantages over present antiplatelet
      agents (i.e., aspirin and ticlopidine). Novel tricyclic nonpeptidal GPIIb/IIIa
      antagonists have been prepared and evaluated in vitro as antagonists of
      fibrinogen binding to the purified GPIIb/IIIa receptor and as inhibitors of
      platelet aggregation. The work presented demonstrates the robustness of the
      benzodiazepinedione (BZDD) scaffold, which can be functionalized at the N1-C2
      amide as well as at C7, to provide structural diversity and allow optimization of
      the physiochemical and pharmacological properties of the BZDD based GPIIb/IIIa
      antagonists. In addition, the resulting new class of tricyclic GPIIb/IIIa
      antagonists could be used to probe for additional binding interactions on the
      GPIIb/IIIa receptor and perhaps lead to BZDD based GPIIb/IIIa antagonists with
      increased potency. The tricyclic molecules reported herein demonstrate that a
      heterocyclic ring can be fused to the benzodiazepinedione scaffold with retention
      of anti-aggregatory potency and in the case of tetrazole 30i, increased potency
      relative to the bicyclic analogue 1c.

PMID- 9925296
TI  - Synthesis and pharmacology of the isomeric methylheptyl-delta8
      tetrahydrocannabinols.
AB  - The synthesis of the 3-heptyl, and the eleven isomeric 3-methylheptyl-delta8
      tetrahydrocannabinols (3-7, R and S methyl epimers, and 8) has been carried out.
      The synthetic approach entailed the synthesis of substituted resorcinols, which
      were subjected to acid catalyzed condensation with trans-para-menthadienol to
      provide the delta8-THC analogue. The 1'-, 2'- and 3'-methylheptyl analogues (3-5)
      are considerably more potent than delta8-THC. The 4'-, 5'- and 6'-methylheptyl
      isomers (6-8) are approximately equal in potency to delta8-THC.

PMID- 9925297
TI  - Synthesis of some thieno gamma lactam monocarboxylic acids with high
      antibacterial activity: a new look at an old molecular system.
AB  - Synthesis and antibacterial activity of some novel monocyclic thienyl gamma
      lactams are reported. The compounds have been synthesized by a two-step process
      consisting of, first, intermolecular Michael addition, followed by intramolecular
      amidification between suitable arylamino malonate and 3-(2'-thienyl) acryloyl
      chloride and then hydrolysis cum in situ decarboxylation of the diacid. The
      compounds showed moderate to high antibacterial activity against gram positive
      and gram negative bacteria.

PMID- 9925298
TI  - Syntheses of amino nitrones. Potential intramolecular traps for radical
      intermediates in monoamine oxidase-catalyzed reactions.
AB  - Monoamine oxidase (MAO) is a flavin-dependent enzyme that catalyzes the oxidative
      deamination of a variety of amine neurotransmitters and toxic amines. Although
      there have been several studies that support the intermediacy of an amine radical
      cation and an alpha-radical during enzyme catalysis, there is no direct, i.e.
      EPR, evidence for these species as they are formed. Amino nitrones have been
      designed which, upon radical formation would produce an intermediate that is a
      resonance structure of the corresponding nitroxyl radical, which should be
      observable by EPR spectroscopy. Syntheses of seven different amino nitrones,
      three acyclic, and four cyclic analogues were attempted. The protected amino
      nitrones were stable, but all three of the acyclic amino nitrones were unstable.
      One of the cyclic analogues was very stable (39), one was stable only in organic
      solvents (40), one was stable only in aqueous medium below pH 6.5 (41), and the
      other (42) was stable for just a short time at room temperature, decomposing to a
      stable free radical. None of these analogues produced a MAO-catalyzed radical,
      yet 41 is a poor substrate (Km=0.2mM; k(cat) = 0.034 min-1) and 39 is a mixed
      inhibitor (Ki = 26.5 mM). Although this approach does not appear to be applicable
      to amino nitrones, it should be a valuable approach for other enzymes where
      radical intermediates are suspected and nonamine nitrones can be utilized.

PMID- 9925299
TI  - The design, synthesis, and evaluation of novel conformationally rigid analogues
      of sialyl Lewis(x).
AB  - The design and synthesis of a series of analogues of sialyl Lewis(x)(1) which
      incorporate conformationally rigid tetralin and naphthalene ring systems(2-4) has
      led to novel compounds which have similar potency to 1 as inhibitors of cell
      adhesion.

PMID- 9925300
TI  - Indole and benzimidazole derivatives as steroid 5alpha-reductase inhibitors in
      the rat prostate.
AB  - A novel series of indole and benzimidazole derivatives were synthesized and
      evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among
      these compounds, 4-?2-[1-(4,4'-dipropylbenzhydryl)indole-5
      carboxamido]phenoxy?buty ric acid (15) and its benzimidazole analogue 25 showed
      potent inhibitory activities for rat prostatic 5alpha-reductase (IC50 values of
      9.6+/-1.0 and 13+/-1.5 nM, respectively), with the potency very close to that of
      finasteride. Compound 30, in which the moiety between the benzene ring and amide
      bond was replaced by quinolin-4-one ring, showed almost equipotent activity
      (IC50= 19+/-6.2nM) with the correspondent amide derivative 13. This result was
      consistent with the previous observation that the coplanarity of this moiety
      might contribute to the potent inhibitory activity.

PMID- 9925301
TI  - Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3
      arylisoquinoline derivatives.
AB  - In this study a series of 3-arylisoquinoline derivatives were synthesized and
      cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional
      quantitative structure-activity relationship was investigated using the
      comparative molecular field analysis (CoMFA). The results suggested that the
      electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were
      strongly correlated with the antitumor activity. Considerable predictive ability
      (cross-validated r2 as high as 0.721) was obtained through CoMFA.

PMID- 9925302
TI  - Hybrid peptides constructed from RES-701-1, an endothelin B receptor antagonist,
      and endothelin; binding selectivity for endothelin receptors and their
      pharmacological activity.
AB  - Hybrid peptides were constructed from endothelin B receptor (ET(B)) selective
      antagonist RES-701-1 (1) and endothelin (ET-1). They have N-terminal 10 amino
      acids derived from 1 and C-terminal 10 amino acids derived from ET-1. RES-701-1(1
      10)-[Ala15]ET-1(12-21) and its analogues substituted or truncated at the residues
      derived from RES-701-1 had proved to possess high receptor binding activity
      selective for ETB as well as 1. Substitutions at the residues derived from ET-1
      had produced some analogues that possessed high affinity not only for ETB but for
      ETA. Although all analogues had antagonistic effects on ETA, some analogues had
      proved to function as agonist on ETB confirmed by the changes in intracellular
      calcium concentrations of ET receptor-transfected COS-7 cells. We have found four
      types of ET receptor-binding peptides: (1) ETB-selective agonist with weak ETA
      antagonism (3, KT7421); (2) ETB-selective antagonist with weak ETA antagonism
      (29, KT7539); (3) ETB agonist with potent ETA antagonism (27, KT7538); and (4)
      non-selective ETA/ETB antagonist (26, KT7540).

PMID- 9925303
TI  - Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate
      modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3-and
      5-end-modification, with anti-HIV-1 activity.
AB  - We have found that a hexadeoxyribonucleotide (5'TGGGAG3', R-95288), Koizumi, M.
      et al. Bioorganic & Medicinal Chemistry, 1997, 5, 2235, bearing a 3,4
      dibenzyloxybenzyl (3,4-DBB) group at the 5'-end and a 2-hydroxyethylphosphate at
      the 3'-end, has high anti-HIV-1 activity and the least cytotoxicity in vitro and
      in vivo. In order to synthesize more potent hexadeoxyribonucleotides, we
      substituted phosphodiester (P-O) bonds in the 6-mer with the least
      phosphorothioate (P-S), phosphoramidate (P-N), or methylphosphonate (P-Me) bonds.
      When more than two P-N or P-Me bonds were introduced into a 6-mer, the phosphate
      modified 6-mers had weak or no anti-HIV- activity, in spite of quadruplex
      structure formation. However, when P-S bonds were substituted for P-O bonds, anti
      HIV-1 activity of their 6-mers did not dramatically decrease, compared with
      compounds substituted with P-N or P-Me bonds. The results suggest that the
      formation of a quadruplex structure is not always sufficient for anti-HIV-1
      activity of the 6-mer, and that net negative charges derived from P-O or P-S
      bonds in the quadruplex are important for anti-HIV-1 activity. Moreover, among
      various phosphate-modified ODNs, we found that the anti-HIV-1 activity of ODN PS7
      with only one P-S bond was the same as that of R-95288, both having a high
      stability in human plasma.

PMID- 9925304
TI  - Structure-based design, synthesis and evaluation of conformationally constrained
      cysteine protease inhibitors.
AB  - The inhibition of cysteine proteases is being studied as a strategy to combat
      parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain
      is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of
      Chagas' disease. A crystal structure of cruzain, covalently inactivated by
      fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to
      design potential inhibitors. Conformationally constrained gamma-lactams
      containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone
      (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of
      ca. 20 nM against the Leishmania major protease and ca. 50 nM versus falcipain,
      an important cysteine protease isolated from Plasmodium falciparum. However, all
      of the conformationally constrained inhibitors were weak inhibitors of cruzain,
      compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors
      (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent
      second order inhibition rate constant (k(inact)/Ki) of 634,000s(-1)M(-1). A
      significant reduction in activity was also observed with acyclic inhibitors 30
      and 51 containing alpha-methyl phenylalanine residues at the P2 position. These
      data indicate that the pyrrolidinone ring, especially the quarternary center at
      P2, interferes with the normal substrate binding mode with cruzain, but not with
      falcipain or the leishmania protease.

PMID- 9925305
TI  - Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the
      related methano analogues. Remarkable effect of the nucleobases and the
      cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase.
AB  - A series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2a,b
      and (Z)-2a,b, as well as the related methano analogues (+/-)-3a,b and (+/-)-4a,b
      were prepared for evaluation of their PNP inhibitory activities. The cyclopopane
      ring and the hypoxanthine residue were found to increase the profile of
      inhibitory activity. The IC50 and Ki values of difluoro?(1R*,2S*)-2-[2-(6-oxo-6,9
      dihydro-1H-9-purinyl)ethyl]cycl opropyl?methylphosphonic acid (+/-)-3b toward PNP
      purified from Cellulomonas sp. were determined to be 70 nM and 8.8 nM,
      respectively.

PMID- 9925306
TI  - CH/pi interactions in the crystal structure of class I MHC antigens and their
      complexes with peptides.
AB  - The crystal structure of class I major histocompatibility complex antigens (MHC)
      bound to their specific ligand peptides were analyzed, in the context of the
      CH/pi interaction, with use of a computer program CHPI. A number of short CH/Csp2
      distances have been shown at the boundary of the heavy chain and beta2
      microglobulin. These interactions are conserved between species, human versus
      murine. A number of contacts shorter than the conventional van der Waals distance
      have been disclosed between CH hydrogens and aromatic side-chain groups in the
      MHC/peptide complexes. The CH/pi interaction has been suggested to contribute to
      the specificity in the complex formation of class I MHC.

PMID- 9925307
TI  - Syntheses and preventive effects of analogues related to 1alpha,25-dihydroxy
      2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) on bone mineral loss in ovariectomized
      rats.
AB  - Analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED
      71) (2), 26,27-dimethyl ED-71 (3) and 26,27-diethyl ED-71 (4), were synthesized
      from lithocholic acid (5). In the study of the preventive effects of these
      analogues and ED-71 (2) on bone mineral loss in ovariectomized rats, 26,27
      dimethyl ED-71 (3) showed the most potent activity.

PMID- 9925308
TI  - Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine
      esters as potential prodrugs of acyclovir.
AB  - 2-Amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a
      d were synthesized as potential prodrugs of acyclovir, and were evaluated for
      their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in
      HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2
      hydroxyethoxymethyl)purine (3) with trimethylamine in THF/DMF (4:1) followed by a
      reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2
      in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O,
      (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) in DMF in the presence of a catalytic amount
      of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the
      prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary
      recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%)
      and comparable to that of valacyclovir (50%). The prodrug 4d protected dose
      dependently the mortality of HSV-1-infected mice, and the group treated with 4d
      at a dose of 400 mg/kg showed the longest mean survival day (14.6+/-3.1 days)
      (mean+/-S.D.).

PMID- 9925309
TI  - Rat liver microsomal enzyme catalyzed oxidation of 1-cyclopropyl-4-phenyl-1,2,3,6
      tetrahydropyridine.
AB  - NADPH supplemented rat liver microsomal enzyme preparations catalyze the
      conversion of 1-cyclopropyl4-phenyl-1,2,3,6-tetrahydropyridine to the p
      hydroxyphenyl (low yield), descyclopropyl (high yield) and 2,3-dihydropyridinium
      and, subsequently, pyridinium (intermediary yield) metabolites. When the methine
      proton of the cyclopropyl group was replaced with a deuteron, a normal deuterium
      isotope effect (1.4) was observed on the formation of the decyclopropylated
      metabolite and an inverse isotope effect (0.6) on the dihydropyridinium
      metabolite. A larger deuterium isotope effect (3.6) was observed on the ring
      alpha-carbon oxidation pathway with the 2,2,6,6-d4 analogue as substrate. These
      results and the observation that the ratios of the rates of these two alpha
      carbon oxidation pathways are independent of initial substrate concentrations
      suggest that both pathways are catalyzed by the same active site of one form of
      P450. These transformations are discussed in terms of metabolic pathways that
      have been proposed for the cytochrome P450 catalyzed alpha-carbon oxidation of
      amines.

PMID- 9925310
TI  - Effects of parent Shamo cocks on the histochemical properties of M. iliotibialis
      lateralis and M. supracoracoideus on their crossbred broilers.
AB  - 1. Four Shamo (a Japanese game bird) cocks showing different characteristics in
      the histochemical properties of M. iliotibialis lateralis (ITL) were crossed with
      White Rock hens to produce male and female crossbred broilers of the 4 lines (90
      d of age). Normal broilers (56 d) were used, for comparison. 2. Histochemical
      properties of ITL and M. supracoracoideus (SC) were compared among the crossbred
      lines and normal broilers. Myofibres were divided into Types II R, II I and II W
      showing high, moderate and low reduced nicotinamide adenine dinucleotide
      dehydrogenase (NADH-DH) activities, respectively. 3. In the ITL of the crossbred
      cockerels, the percentage of Type II R and II I fibres decreased and conversely
      Type II W increased in comparison to those in the Shamo. 4. Sex differences of
      the histochemical properties were recognised only in the ITL of the crossbred, in
      which the percentage of Type II R fibres was greater in the male. 5. The
      different characteristics of the parent Shamo cocks were reproduced only in the
      different fibre type composition of the ITL muscle in the crossbred cockerels. 6.
      The histochemical features of fibre type seemed to develop with bird age,
      particularly subsarcolemmal accumulation of formazan granules (indicating high
      NADH-DH activity) in Type IIR fibres. 7. Breed, line, sex and age differences in
      the histochemical properties were demonstrated clearly in ITL but not in SC.

PMID- 9925311
TI  - Assessment of alpha-tocopheryl acetate supplementation, addition of salt and
      packaging on the oxidative stability of raw turkey meat.
AB  - 1. One-day-old turkey poults (n = 14) were randomised into 2 groups (n = 7) and
      fed diets containing 20 (E20) and 600 (E600) mg all-rac-alpha-tocopheryl
      acetate/kg food for 21 weeks prior to slaughter. Two batches were formed from E20
      meat (E20) and E20 plus 10 g salt/kg (E20S). Two similar batches were formed from
      E600 meat (E600) and E600 plus 10 g salt/kg (E600S). 2. The effects of alpha
      tocopheryl acetate supplementation and salt addition on the oxidative stability
      of raw turkey patties was investigated during aerobic and vacuum-packaged
      refrigerated (4 degrees C) storage. 3. Dietary alpha-tocopheryl acetate
      supplementation reduced TBARS (thiobarbituric acid reacting substances) numbers
      for raw overwrapped and vacuum-packaged turkey leg and breast patties. 4. Dietary
      alpha-tocopheryl acetate had the greatest influence on TBARS numbers for raw
      overwrapped turkey leg patties. 5. The addition of 10 g salt/kg increased TBARS
      numbers for overwrapped and vacuum-packaged turkey leg and breast patties. 6.
      Vacuum-packaged patties remained more oxidatively stable than similarly treated
      overwrapped patties throughout the experimental period.

PMID- 9925312
TI  - Strategies to improve the nutritive value of rice bran in poultry diets. III. The
      addition of inorganic phosphorus and a phytase to duck diets.
AB  - 1. In the first of 2 experiments ducklings grown from 2 to 19 d were given diets
      with 0, 200 or 400 g rice bran, with or without a phytase and with 1 or 3 g
      inorganic phosphorus (Pi) per kg for rice bran-based diets only. In the 2nd
      experiment rice bran concentrations were 0, 300 or 600 g rice bran per kg with or
      without a phytase and 1 g Pi/kg. Ducks were grown from 19 to 40 d of age. 2. In
      experiment 1, a response to phytase was observed for weight gain and food intake
      on most diets except those with 200 g rice bran (3 g Pi) and 4.00 g rice bran (1
      g P)i/kg. Main effects showed that 400 g rice bran depressed growth rate and food
      conversion ratio (FCR); increasing Pi depressed food intake, while food phytase
      increased food intake and growth rate over 2 to 19 d. There were several
      interactions. Dry matter and P retention were reduced but N digestibility
      improved when rice bran was increased from 200 g to 400 g/kg at 2 to 10 d of age;
      apparent metabolisable energy (AME) and calcium retentions were improved, similar
      results being seen at 10 to 19 d of age. Calcium and P retentions increased with
      the addition of food phytase and, at 10 to 19 d of age, phytase increased dry
      matter digestibility. Increasing Pi improved calcium and P retention, but only at
      2 to 10 d of age. 3. Tibia ash (g or g/kg) content of bone was lowest on the diet
      without rice bran and without phytase; Pi concentration had no effect but phytase
      increased tibia ash on diets with 0 and 200 g rice bran and 1 g Pi/kg. Retention
      of several minerals in tibia ash declined at the highest rice bran inclusion
      rate; Pi level and phytase both increased Mg retention. 4. In experiment 2, food
      intake and growth rate of ducks, but not FCR, declined as rice bran inclusion
      increased from 0 to 600 g/kg. Phytase improved growth rate but not food intake
      and FCR on all 3 diets. Dry matter digestibility declined with increasing rice
      bran inclusion, but AME increased; retention of P and Mg declined but those of Ca
      and Fe increased. Phytase improved dry matter digestibility and retention of N
      and P. AME also increased but this was only on diets with 0 and 600 g rice
      bran/kg. There were reductions of 8% and 10% in P excreted in experiments 1 and 2
      respectively when food phytase was added. 5. Tibia ash declined with increasing
      dietary inclusion of rice bran. Zn and Mn in ash tended to decline and Mg to
      increase; Ca and P showed no change in concentration in tibia ash. Again, phytase
      increased tibia ash content in bone. 6. It was concluded that there were a number
      of unexpected benefits from adding a food phytase to these diets, which resulted
      in improved nutrient yield and bird performance, although several of the diets
      appeared to be adequate in available P.

PMID- 9925313
TI  - Strategies to improve the nutritive value of rice bran in poultry diets. IV.
      Effects of addition of fish meal and a microbial phytase to duckling diets on
      bird performance and amino acid digestibility.
AB  - 1. Ducklings were given diets with vegetable protein (VP) and 0 or 600 g rice
      bran/kg; fish meal (60 g/kg) and a phytase (+, -) were added to the diets (VP +
      AP). An additional 40 g soyabean meal/kg was added to the diet with rice bran (VP
      ++). Amino acid digestibility and mineral retention were measured in the lower
      ileum of ducklings killed at 23 d of age. Acid insoluble ash was used as an inert
      marker. Trypsin and amylase activities were also measured and weights of the
      pancreas and small intestine recorded at slaughter. 2. Addition of soyabean meal
      (VP ++) to the diet with rice bran improved growth rate and food intake compared
      to the diet without (VP) and gave the same food intake and growth rate as the
      comparable basal diet (VP) without rice bran. Fish meal improved growth rate on
      the diets without rice bran and improved food intake on this diet (VP + AP). Rice
      bran depressed growth rate and food conversion ratio (FCR); protein source
      affected growth rate, food intake and FCR; phytase increased food intake only.
      There were several interactions. 3. Determined total amino acid composition of
      the diets appeared to meet the essential amino acid requirements of ducklings.
      Rice bran depressed the ileal digestibility of virtually all amino acids and
      phytase had no direct effect, although there were interactions. Fish meal
      addition to diets with rice bran improved the apparent digestibility of several
      essential amino acids as well as that of dry matter and crude protein. 4. Ileal
      retention of some minerals and tibia ash content were reduced by rice bran. Fish
      meal and phytase inclusion increased P retention and ash in tibia. 5. Higher
      intestinal trypsin activity and increased pancreas size were seen in ducklings on
      diets with rice bran compared to those without. Intestinal amylase activity was
      reduced in ducklings given rice bran, probably because of its low starch content.
      6. The stimulating effect of fish meal on duckling performance was probably
      caused in part by the improvement in the digestibility of some amino acids. The
      addition of small amounts of minerals in fish meal may have increased mineral
      retention. Phytase gave benefits anticipated from our previous work, but also
      improved lysine and threonine digestibility in diets containing vegetable protein
      only.

PMID- 9925314
TI  - Effects of sweet, bitter and soaked micronised bitter lupins on duckling
      performance.
AB  - 1. The feeding value of sweet white lupins (Lupinus albus variety Hanli), bitter
      lupins (Lupinus angustifolius) and soaked micronised bitter lupins on male Pekin
      duckling performance was examined. 2. Four isocaloric and isonitrogenous diets
      were formulated with 1 containing no lupin and the other 3 containing 400 g/kg
      sweet, bitter or soaked micronised bitter lupins. The 3 lupin diets were then
      blended appropriately to produce 16 experimental diets containing 0, 50, 100,
      200, 300 and 400 g/kg sweet, bitter and soaked micronised bitter lupins, and fed
      to Cherry Valley Super M Pekin ducklings for 6 weeks. 3. The feeding of bitter
      lupins to ducklings at 200, 300 and 400 g/kg diet resulted in a poorer
      performance (P < 0.01) with regard to body weight gain, food intake and food
      conversion ratio than feeding the control diet. Carcase moisture was higher and
      carcase fat content lower (P < 0.01) at the 400 g/kg concentration only. No
      significant differences were observed with carcase protein or carcase ash
      content. No significant differences were observed between treatments and the
      control when different amounts of sweet or soaked micronised bitter lupins were
      fed. 4. There were significant linear adverse responses (P < 0.01) with bitter
      lupins in most of the variables studied whereas no responses were observed with
      sweet or soaked micronised bitter lupins as the concentration of lupins in the
      diet increased. The soaked micronised bitter lupins performed as well as the
      sweet lupins, showing that the amount of bitter lupins used in duckling diets can
      be increased to 400 g/kg after this treatment.

PMID- 9925315
TI  - Effect of season and dietary energy concentration on composition and strength of
      skin in naked neck fowl.
AB  - 1. Two experiments, in spring and summer, were conducted to evaluate the effect
      of dietary energy concentration on the composition and strength of the skin of
      naked neck fowl. The heterozygous naked neck birds were also compared with their
      normally feathered sibs under summer temperatures. 2. The average temperatures
      were 21.2 degrees C and 27.1 degrees C in spring and summer experiments,
      respectively. Three concentrations of dietary energy were fed to the birds. The
      diets used were: a low energy diet of 12.12 MJ ME/kg; a medium energy diet of
      12.96 MJ ME/kg; and a high energy diet of 13.79 MJ ME/kg. Two protein
      concentration per energy treatment, 230 and 200 g/kg, respectively were used from
      0 to 3 and 3 to 7 weeks of age. 3. A significant season sex interaction showed
      that the skin of males had higher protein and collagen and lower dry matter and
      fat content than that of females, when grown under summer conditions. No sex
      differences were present under spring conditions. 4. The differences between
      sexes was not significant in spring but males had stronger skin than females in
      summer. Neither ambient temperature nor dietary energy concentration
      significantly affected skin displacement of naked neck birds. 5. In comparing the
      naked neck and their normally feathered sibs in the summer experiment, it was
      found that naked neck birds had lower skin fat content and higher skin protein
      content than normally feathered birds.

PMID- 9925316
TI  - Influence of dietary energy on bird performance, carcase parts yields and
      nutrient composition of breast meat of heterozygous naked neck broilers reared at
      natural optimum and summer temperatures.
AB  - 1. Heterozygous naked neck birds were raised under natural spring (average 21.2
      degrees C) and summer temperatures (average 27.1 degrees C) to investigate the
      influence of dietary energy on broiler performance, carcase yield and nutrient
      composition of breast meat. 2. Birds were fed on a low energy diet of 12.12 MJ
      ME/kg, a medium energy diet of 12.96 MJ ME/kg and a high energy diet of 13.79 MJ
      ME/kg with 2 protein concentrations per energy treatment, 230 and 200 g/kg, from
      0 to 3 and 3 to 7 weeks of age, respectively. 3. Summer rearing resulted in a
      decrease in body weight, body weight gain, carcase weight and carcase part yields
      of birds. 4. Increasing dietary energy from 12.12 to 13.79 MJ ME/kg increased
      body weight at 3 and 7 weeks, body weight gains from 0 to 3 and 3 to 7 weeks,
      carcase weights and relative abdominal fat weights of birds in a linear manner.
      There was no effect of dietary energy on the nutrient composition of breast meat.
      5. It was concluded that there was no differences in dietary energy requirements
      of heterozygous naked neck birds when grown under natural optimum (21.2 degrees
      C) and summer temperatures (27.1 degrees C).

PMID- 9925317
TI  - Optimum dietary arginine:lysine ratio for broiler chickens is altered during heat
      stress in association with changes in intestinal uptake and dietary sodium
      chloride.
AB  - 1. The effects of varying the dietary arginine:lysine (Arg:Lys) ratio for broiler
      chickens at thermoneutral and high temperatures was studied in a series of 5
      experiments which measured intestinal epithelial transport or evaluated growth
      and food efficiency with practical diets or diets supplemented with L-arginine
      free base. 2. The growth studies showed that increasing the Arg:Lys ratio at high
      temperatures produced consistent improvements in food conversion without any loss
      in growth. 3. Increasing dietary sodium chloride concentration reduced the
      Arg:Lys ratio necessary for optimum food conversion. 4. Food conversion responses
      were improved whether L-arginine free base was used as a dietary supplement in
      place of an inert filler or practical diets with differing ingredients were used
      to vary the Arg:Lys ratio. 5. In the presence of an equimolar concentration of
      lysine the uptake of arginine by the intestinal epithelium of heat-stressed
      broilers was reduced significantly compared with that of broilers at
      thermoneutral temperatures. 6. The results indicate that the ideal amino acid
      balance for broilers varies with ambient temperature.

PMID- 9925318
TI  - Neem (Azadirachta indica) kernel meal in the diet of White Leghorn layers.
AB  - 1. Neem kernel meal (NKM) was incorporated into a standard layer diet at 0, 100,
      150 and 200 g/kg, replacing parts of the soyabean meal and deoiled rice bran.
      Each diet was offered to 18 White Leghorn layers (25 weeks, 50% egg production)
      in individual cages for a period of 12 weeks. 2. Results indicated significantly
      lower food intakes (P < 0.01), rates of egg production and egg weights in birds
      fed on the diets with NKM at 150 and 200 g/kg. Fertility and hatchability were
      also adversely affected by the higher inclusion rates of NKM. 3. Except for lower
      egg shell weight and shell thickness (P < 0.05) in hens fed NKM at 150 and 200
      g/kg, the internal egg quality characteristics were comparable in all groups. 4.
      Feeding NKM beyond 100 g/kg to laying hens significantly (P < 0.01) reduced the
      content of haemoglobin, erythrocyte count, packed cell volume, serum calcium and
      uric acid concentrations. However, the leucocyte count, plasma glucose
      concentration and serum glutamate oxaloacetate transaminase activity were
      unaltered. Serum glutamate pyruvate transaminase activity was significantly (P <
      0.05) reduced in birds fed NKM at 200 g/kg. 5. Thus NKM at 100 g/kg in a layer
      diet would appear to be safe and cost-effective.

PMID- 9925319
TI  - Oviposition patterns and plasma melatonin rhythms in response to manipulations of
      the light:dark cycle.
AB  - 1. In 2 experiments with Single Comb White Leghorn hens, the effects of different
      light:dark cycles (LD-cycles) upon oviposition patterns and plasma melatonin
      rhythms were studied. In experiment 1, a 28-h ahemeral LD-cycle (12L:16D) was
      used. In experiment 2, a normal 24-h LD-cycle (16L:8D) was applied and the
      effects of a sudden 8-h forward or backward shift of the 8-h dark period (that is
      phase-advanced or phase-delayed LD-cycle) were studied. 2. The oviposition
      patterns as well as the plasma melatonin rhythms were fully synchronised with
      both LD-cycles (24-h or 28-h). The 2 rhythms were gradually re-synchronised after
      phase shifts, and the melatonin response phase-led the oviposition response by 2
      cycles. Thus, the change of the melatonin rhythm coincided with the change of the
      (presumed) open period for LH-release. 3. In the unchanged 24-h LD-cycle,
      ovipositions occurred almost exclusively (98.9%) during light hours, whereas in
      the 28-h LD-cycle, ovipositions occurred primarily (84.5%) during the last 9 h of
      the dark period. 4. In both LD-cycles and after changes of the LD-cycle, light
      always suppressed plasma melatonin, regardless of previous light history. During
      dark periods, concentrations were elevated but, interestingly, only if darkness
      had also been experienced during the same time period 24 h earlier. This
      indicates that light has a direct inhibiting effect upon pineal melatonin
      release, while actual melatonin release during darkness is controlled by an
      endogenous clock.

PMID- 9925320
TI  - Effect of constant and of changing photoperiod on plasma LH and FSH
      concentrations and age at first egg in layer strains of domestic pullets.
AB  - 1. ISA Brown pullets were transferred from 8 to 14 h or from 14 to 8 h
      photoperiods at 35 or 56 d of age. Controls were maintained on constant 8 or 14 h
      photoperiods from day 1. 2. Blood samples were obtained immediately before each
      daylength change and subsequently at 7 d intervals until 1st egg in the treated
      groups and at 70 d of age and then at 14 d intervals until 1st egg in the
      constant photoperiod controls. Plasma luteinising hormone (LH) and follicle
      stimulating hormone (FSH) concentrations were determined using homologous
      radioimmunoassays. 3. Prior to 16 weeks, LH was consistently higher in birds on
      constant 14 h photoperiods than in those on constant 8 h, but was down-regulated
      as birds approached maturity so that LH concentrations in the 2 groups were
      similar during the final 10 d before the first egg was laid. FISH concentrations
      rose steadily with age but with a tendency for concentrations to be higher in the
      8 h than in the 14 h treatment. Birds on constant 8 h daylengths matured 18.3 d
      later than those on constant 14 h photoperiods. 4. A 6 h increment in photoperiod
      given at 35 d or 56 d, resulted in an increase in LH within 7 d in both cases.
      FSH concentration did not respond to an increase in photoperiod at 35 d but rose
      following the same increase at 56 d. This was associated with a 3-week advance in
      sexual maturity, whilst age at 1st egg in birds photostimulated at 35 d was
      similar to the age with a constant 14 h photoperiod. 5. LH concentration fell
      when photoperiod was reduced from 14 to 8 h at either 35 or 56 d and remained
      below the constant 8 h controls for many weeks before rising to a concentration
      not significantly different from other groups in the final 10 d before 1st egg.
      FSH concentrations in birds exposed to a decreased daylength at 35 d, although
      more oscillatory, were similar to the constant 8 h photoperiod controls. In birds
      exposed to the same decrease at 56 d, FSH concentration initially tumbled but was
      similar in the 2 groups during the latter stages of rearing; neither differed
      significantly from the constant daylength controls during the 60 d before 1st
      egg. Sexual maturity in both groups given a reduction in photoperiod was delayed
      by about 2 weeks compared with constant 8 h controls. 6. Change in FSH
      concentration following an increase in daylength was a better predictor of age at
      1st egg than change in LH. However, FSH concentrations after 14 weeks of age were
      rather similar in short day and long day controls and in the 2 groups given
      reductions in photoperiod at 35 d and 56 d, despite differences of nearly 5 weeks
      in mean age at 1st egg amongst these 4 treatments.

PMID- 9925321
TI  - Performance, incidence of metabolic disturbances and endocrine variables of food
      restricted male broiler chickens.
AB  - 1. This experiment was carried out to evaluate the productive and physiological
      consequences of a slight but long term food restriction of male broiler chickens
      from 2 commercial strains. 2. Cobb-500 and Ross chickens were submitted to a 20%
      food restriction from 8 to 21 d of age. Strain, food programme and their
      interactive effects were analysed in terms of consequences upon performance,
      mortality, incidence of sudden death syndrome (SDS) and ascites syndrome (AS),
      index of right cardiac hypertrophy and plasma concentrations of hormones related
      to metabolism and growth (T3, T4, T3:T4 ratio, IGF-I and GH). 3. Although some
      catch-up growth was observed by refeeding previously restricted birds after 22 d
      of rearing, food restriction decreased (P < or = 0.05) body weight at market age
      (42 d) irrespective of the strain, but improved (P < or = 0.05) food conversion.
      4. The incidence of mortality was not high in non-restricted birds but SDS and AS
      caused more than 50% of deaths. Hypertrophic cardiac index was observed in
      chickens of both strains after 4 weeks of age and was higher in ad libitum fed
      birds. 5. During the period of food restriction, plasma T3 and IGF-I
      concentrations decreased whereas plasma T4 and GH concentrations increased
      compared to those of the age-matched ad libitum fed counterparts. During the
      subsequent ad libitum feeding period, few differences in circulating hormone
      concentrations were observed, except for the higher mean GH litres in previously
      food-restricted chickens at 35 d of age. 6. These results indicate that even a
      non-severe food restriction negatively affects body weight of 42-d-old male
      broilers but these are benefits with improved food efficiency and diminished
      mortality from metabolic disturbances. The hormone results suggest that the
      degree of food restriction applied was not severe because there was a very fast
      adaptive response with small and transient alterations in T3, T4 and GH plasma
      concentrations during the period of compensatory growth.

PMID- 9925322
TI  - Refeeding increases hepatic insulin-like growth factor-I (IGF-I) gene expression
      and plasma IGF-I concentration in fasted chicks.
AB  - 1. We examined the influence of refeeding after 2 d of fasting on plasma insulin
      like growth factor-I (IGF-I) concentration and hepatic IGF-I gene expression in
      chickens at 6 weeks of age. 2. Hepatic IGF-I mRNA was measured by ribonuclease
      protection assay and plasma IGF-I concentration was determined by
      radioimmunoassay. 3. Plasma IGF-I concentration decreased following fasting,
      increased to the level of fed controls after 2 h of refeeding but then fell back
      to the level of fasted chickens after 6 h of refeeding. 4. Fasting reduced
      hepatic IGF-I mRNA concentrations to less than half of those in the fed controls.
      Refeeding increased IGF-I mRNA sharply at 2 h after refeeding, but by 6 h after
      refeeding they had taller back again to levels significantly lower than at 2 h.
      5. A significant correlation between plasma IGF-I concentration and hepatic IGF-I
      gene expression was found, suggesting that when chicks are refed after 2 d of
      fasting, the short-term increase in plasma IGF-I concentration may be partly
      regulated by the alteration in hepatic IGF-I mRNA.

PMID- 9925323
TI  - Tissue concentrations of sulphaquinoxaline administered in the food of laying
      hens.
AB  - 1. Sulphaquinoxaline (SQ) was fed to laying hens at a dietary level of 400 mg/kg
      for 3 successive days. SQ contents (mg/kg) in the blood, kidney, liver, ovary,
      muscle (thigh) and adipose tissue collected on 1, 2, and 3 d after the start of
      feeding were determined by HPLC. The relationship between the SQ content in the
      tissues and times (d) of SQ feeding was analyzed statistically. 2. Dietary SQ was
      distributed throughout the whole body. 3. Contents in tissues, except the kidney,
      had already reached a plateau by day 1 after the start of administration whereas
      in the kidney it increased linearly throughout the 3 days. 4. The plateau values
      of SQ in the tissues were much greater than those of sulphamonomethoxine and
      sulphadimethoxine.

PMID- 9925324
TI  - Changes in the somatosensory evoked potentials and spontaneous
      electroencephalogram of broiler chickens during exposure to gas mixtures.
AB  - 1. Six week-old broiler chickens implanted with electroencephalogram (EEG)
      recording and somatosensory stimulating electrodes were exposed to either 90%
      argon in air, a mixture of 30% carbon dioxide and 60% argon in air or a mixture
      of 30% oxygen and 40% carbon dioxide (balance nitrogen) for 2 min, to determine
      the times to onset of changes in spontaneous EEG and the loss of somatosensory
      evoked potentials (SEPs) and thus unequivocal loss of consciousness. 2. In
      addition, after a 2 min exposure to the carbon dioxide-oxygen mixture, some
      broilers were allowed to recover in air and their EEGs and SEPs were continuously
      recorded until the return of normal EEG and SEPs. During this period, the time to
      return of response to comb pinching was also determined in 10 broilers. 3. All
      broilers exposed to either argon or the carbon dioxide-argon mixture died within
      2 min, whereas, only 3 out of 17 broilers died during the 2 min exposure to the
      carbon dioxide-oxygen mixture. 4. During exposure to argon, unlike the other 2
      gas mixtures, the majority of broilers showed high amplitude, low frequency
      electrical activity in the EEG on average at 10 s. The mean times to onset of EEG
      suppression were 17, 19 and 40 s after exposure to argon, the carbon dioxide
      argon mixture and the carbon dioxide-oxygen mixture, respectively. An isoelectric
      EEG occurred on average at 58 and 41 s after exposure to argon and the carbon
      dioxide-argon mixture, respectively. An isoelectric EEG did not occur in broilers
      which were exposed to the carbon dioxide-oxygen mixture. 5. The SEPs were
      abolished in broilers on average 32 and 24 s after exposure to argon and the
      carbon dioxide-argon mixture, respectively. During exposure of broilers to the
      carbon dioxide-oxygen mixture the SEPs were abolished in the majority of birds on
      average at 47 s, however, 2 out of 14 birds retained their SEPs for the entire
      period of 2 min exposure to this gas mixture. 6. During the recovery after
      exposure to the carbon dioxide oxygen mixture, response to comb pinching and SEPs
      returned either at the time of, or soon after, the onset of high frequency
      electrical activity in the suppressed EEG of broilers. The mean times to return
      of response to comb pinching and SEPs were 52 and 43 s, respectively. 7. Based on
      the time to onset of EEG suppression or loss of SEPs, exposure of broilers to
      either 90% argon in air, or a mixture of 30% carbon dioxide and 60% argon in air,
      resulted in quicker loss of consciousness than during exposure to a mixture of
      40% carbon dioxide, 30% oxygen and 30% nitrogen. The time to return of
      consciousness after a 2 min exposure to the carbon dioxide-oxygen mixture was
      also found to be rapid.

PMID- 9925325
TI  - Egg shell colour is affected by laying cage design.
AB  - 1. When laying hens are stressed some retain their eggs in the shell gland beyond
      the normal time of laying and this can result in the deposition of extra
      cuticular calcium which makes brown eggs appear paler. 2. Three different types
      of enriched modified cage were compared: the location where eggs were laid was
      recorded and shell colour was measured using a reflectometer. 3. In 2 types of
      cage with enclosed nest boxes more eggs (80%) were laid in the nests than in a
      design with nest hollows in the open part of the cage (41%). 4. The eggs from the
      cages with enclosed nests were darker (had less extraneous calcium) than those
      with open nest hollows. This implies that in the designs with nest boxes fewer
      eggs had been retained and the hens may have been less stressed. 5. The results
      support previous evidence that to reduce stress and improve welfare it is
      desirable to provide enclosed nest sites for caged laying hens.

PMID- 9925326
TI  - Validation of a high-performance liquid chromatographic method for the
      determination of norfloxacin and its application to stability studies (photo
      stability study of norfloxacin).
AB  - The development and validation study of a sensitive, rapid, reproducible, easy
      and precise reversed-phase high-performance liquid chromatographic assay for
      norfloxacin (NFLX) samples from photo-stability of solid dosage forms, without
      using gradient elution, extraction methods and without using counter-ion has been
      carried out. The method showed excellent linearity (r2> or =0.999) in the range 1
      20 microg ml(-1) using a Lichrosorb-RP-8 column (10 microm, 20 cm x 4.6 mm) and
      UV-detection (278 nm) at ambient temperature. This method showed good efficiency
      for the analysis of photodegraded NFLX samples, and was applied to study the
      photo-stability of NFLX tablets under different conditions (direct sun light,
      ultraviolet light and fluorescent light). It was proven that the use of a
      disintegrant can increase the photo-stability of the NFLX in the tablets. This
      effect was studied in directly compressible tablets with microcrystalline
      cellulose (MCC) and mannitol for direct compression.

PMID- 9925327
TI  - Development of an assay for the extraction and quantification of nine 5-n-alkyl-5
      ethyl barbituric acids in various rat tissues.
AB  - Methods were developed to quantify a series of nine homologous 5-n-alkyl-5-ethyl
      barbituric acids in 15 rat tissues. Tissue homogenates were spiked with one of
      four multicomponent mixtures (methyl to n-propyl, n-propyl to n-pentyl, n-pentyl
      to n-heptyl and n-pentyl to n-nonyl). Liquid-liquid extraction was used to
      extract the homologues from the rat tissues. Reverse phase HPLC with UV detection
      at 214 nm was used to separate and quantify the individual barbiturates. The
      limit of detection for each respective homologue was 1 microg x g(-1) except skin
      and bone (2 microg x g(-1)). The methodology developed reduced a potential 135
      individual assays to a more manageable 16.

PMID- 9925328
TI  - Liquid chromatographic analysis of physostigmine salicylate and its degradation
      products.
AB  - A simple stability-indicating HPLC assay has been developed for physostigmine
      salicylate, capable of following its degradation. A 250 x 5 mm i.d. column packed
      with 10 microm Bondapak C18 was used, with a mobile phase of acetonitrile -
      ammonium acetate (pH 6.0; 0.1 M) (50:50, v/v) and flow rate 1.2 ml x min(-1). All
      peaks are eluted in <10 min and the method has good precision. The optimum
      wavelength for detection of degradation products is 305 nm. Application of the
      assay for a commercial preparation of physostigmine salicylate for injection is
      presented.

PMID- 9925329
TI  - Structure elucidation and conformational properties of synthetic cannabinoids (-)
      2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibe nzo [b,d]pyranyl)-2
      hexyl-1,3-dithiolane and its methylated analog.
AB  - The synthetic cannabinoid (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy
      6H-dibenzo[b,d]+ ++pyranyl)-2-hexyl-1,3-dithiolane (AMG-3) is a cannabimimetic
      molecular probe with one of the highest binding affinities reported to date.
      Therefore, due to its potential pharmacological importance, its structure was
      sought to be elucidated and its conformational properties were studied using a
      combination of 1D, 2D NMR spectroscopy and molecular modelling. The structure of
      its methylated analog (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H dibenzo
      [b,d]pyranyl-1-methoxy)-2-hexyl-1,3 dithiolane (AMG-18), was also studied and its
      conformational properties were compared with AMG-3. AMG-18 lacks of the phenolic
      hydroxyl group a strict requirement for cannabimimetic activity and is almost
      devoid of any biological activity. The conformational analysis studies showed
      that 1',1' dithiolane ring restricted the orientation preferences of alkyl chain.
      This may account for the high binding affinity of AMG-3 to cananbinoid receptors.
      Grid scan search studies showed different preferences of possible adopting
      dihedral values of phenolic hydroxyl group and its methyl ether. These
      observations may account for their differences in biological activity.

PMID- 9925330
TI  - Potentiometric sensor for methylene blue based on methylene blue-silicotungstate
      ion association and its pharmaceutical applications.
AB  - A methylene blue (MB) poly(vinyl chloride) membrane sensor based on MB
      silicotungstate (SLT) ion association as electroactive material was described.
      The linear response covered the range 1 x 10(-3)-1 x 10(-6) mol x dm(-3) MB
      solution, with a slope 52.0+/-0.8 mV decade(-1) (pH range 3.0-10.0). The
      detection limit was 7.65 x 10(-7) mol x dm(-3). The electrode showed stability,
      good reproducibility and fast response. Interferences from common inorganic
      cations, some organic base were negligible. These characteristics of the
      electrode enabled it to be used successfully for the determination of MB in
      injection. There was a good agreement for the results of MB content in injection
      between potentiometric method and USP standard procedure.

PMID- 9925331
TI  - An experimental design approach to the optimisation of a flow injection analysis
      method for glycine.
AB  - A flow injection analysis method for the determination of glycine, based on the
      reaction with ortho-phtalaldehyde and N-acetylcysteine in a basic buffer, was
      optimised. In the first step screening of the variables, to select the most
      important ones, was performed using: (i) a half-fraction factorial design and
      (ii) a quarter-fraction factorial design, for five factors at two levels. The
      effects of the factors on the peak height were calculated from both screening
      designs and compared. For the half-fraction factorial design (resolution IV), the
      significance of the factor effects on the peak height was checked by: (i)
      comparing them with a critical effect, calculated from two-factor interactions
      and based on a t-test, (ii) using a non parametric approach and (iii) drawing a
      normal probability plot. For the quarter-fraction factorial design (resolution
      III) the significance of the effects of the factors on the peak height was
      checked using: (i) a randomization test method, (ii) the non parametric method
      and (iii) a normal probability plot. In the second step, the factor found to be
      of importance was optimised using the uniplex method.

PMID- 9925332
TI  - Spectrophotometric and atomic absorption spectrometric determination of certain
      cephalosporins.
AB  - Two sensitive spectrophotometric and atomic absorption spectrometric procedures
      are developed for the determination of certain cephalosporins (cefotaxime sodium
      and cefuroxime sodium). The spectrophotometric methods are based on the charge
      transfer complex formation between these drugs as n-donors and 7,7,8,8
      tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (p-CA) as pi-acceptors to
      give highly coloured complex species. The coloured products are measured
      spectrophotometrically at 838 and 529 nm for TCNQ and p-CA, respectively. Beer's
      law is obeyed in a concentration range of 7.6-15.2 and 7.1-20.0 microg x ml(-1)
      with TCNQ, 95.0-427.5 and 89.0-400.5 microg x ml-1 with p-CA for cefotaxime
      sodium and cefuroxime sodium, respectively. The atomic absorption spectrometric
      methods are based on the reaction of the above cited drugs after their alkali
      hydrolysis with silver nitrate or lead acetate in neutral aqueous medium. The
      formed precipitates are quantitatively determined directly or indirectly through
      the silver or lead content of the precipitate formed or the residual unreacted
      metal in the filtrate by atomic absorption spectroscopy. The optimum conditions
      for hydrolysis and precipitation have been carefully studied. Beer's law is
      obeyed in a concentration range of 1.9-11.4 and 1.78-8.90 microg x ml(-1) with
      Ag(I), 14.2-57.0 and 13.3-53.4 microg x ml-1 with Pb(II) for cefotaxime sodium
      and cefuroxime sodium, respectively (for both direct and indirect procedures).
      The spectrophotometric and the atomic absorption spectrometric procedures hold
      well their accuracy and precision when applied to the analysis of cefotaxime
      sodium and cefuroxime sodium dosage forms.

PMID- 9925333
TI  - Determination of astemizole, terfenadine and flunarizine hydrochloride by ternary
      complex formation with eosin and lead(II).
AB  - A simple and sensitive spectrophotometric method has been established for the
      determination of astemizole(I), terfenadine(II) and flunarizine
      hydrochloride(III) based on ternary complex formation with eosin and lead(II).
      The method does not involve solvent extraction. The colour of the produced
      complex is measured at 547.5 nm for (I) and (III), while (II) is measured at
      540.7 nm. Appropriate conditions were established for the colour reaction and for
      the eosin: Pb(II): drug ratio to obtain maximum sensitivity. Under the proposed
      conditions, the method is applicable over concentration range of 4.1-37.6, 11.8
      47.2 and 2.4-19.1 microg x ml(-1) with mean percentage recovery of 99.20+/-0.63,
      99.76+/-0.39 and 99.60+/-0.47% for (I), (II) and (III), respectively. The
      suggested method was applied for determination of (I), (II) and (III) in
      pharmaceutical preparations. Through the use of a non-ionic surfactant
      (methylcellulose), prior extraction of the drugs was unnecessary. The results
      obtained demonstrated that the method is equally accurate, precise and
      reproducible as the official or reported methods. For the purpose of enhancing
      the sensitivity, a fluorescence quenching method for determination of the studied
      drugs via ternary complex formation was also investigated. The detection limit
      for the studied drugs (I), (II) and (III) was 0.94-7.1 microg x ml(-1) with mean
      percentage recovery of 99.84+/-0.29, 99.24+/-0.36 and 99.34+/-0.26%,
      respectively. The results obtained by applying the proposed methods were
      statistically analyzed and compared with those obtained by official or reference
      methods. Unlike other reported ion-pair techniques, the suggested methods have
      the advantage of being applicable for the determination of the three drugs in
      their pharmaceutical dosage forms without prior extraction. They are recommended
      for quality control and routine analysis where time, cost effectiveness and high
      specificity of analytical techniques are of great importance.

PMID- 9925334
TI  - Spectrofluorimetric determination of prenalterol hydrochloride in pharmaceutical
      preparations and biological fluids.
AB  - A simple and highly sensitive fluorimetric method was developed for the routine
      determination of prenalterol hydrochloride in bulk, in dosage forms and in
      biological fluids. The method is based on the fluorescence induced by reaction of
      the nitroso-derivative of prenalterol hydrochloride with 2-cyanoacetamide in the
      presence of ammonia. The different experimental parameters were carefully studied
      and incorporated into the procedure. The fluorescence is measured at 440 nm after
      excitation at 368 nm. Fluorescence intensity is a linear function of prenalterol
      hydrochloride concentration over the range of 0.1-2.8 microg x ml(-1) in the
      solution finally measured. A proposal for the reaction pathway was suggested.

PMID- 9925335
TI  - Reversed-phase ion-pair HPLC determination of some water-soluble vitamins in
      pharmaceuticals.
AB  - A reversed-phase ion-pair high-performance liquid chromatografic method (RP-IPC)
      was developed to assay some water-soluble vitamins in solution dosage forms.
      Vitamins of the B-group B1, B2, B3, and B6, including vitamin C were determined
      in Oligovit coated tablets. In Beviplex coated tablets the vitamins B1, B2, B3,
      B6 and p-aminobenzoic acid were analysed. Hexanesulphonic acid sodium salt and
      triethanolamine in water methanol were used as mobile phase with adjusting pH to
      2.8 with orthophosphoric acid. Phenol was used as an internal standard. For
      quantitative simultaneous analysis of vitamins in pharmaceutical formulations,
      the method of internal standard was used. All parameters for the validation of
      the method are given.

PMID- 9925336
TI  - Cathodic adsorptive stripping voltammetric determination of the anti-inflammatory
      drug indomethacin.
AB  - Sensitive voltammetric methods have been developed for the determination of the
      anti-inflammatory, anti-pyretic and analgesic drug indomethacin sodium. The
      methods are based on the controlled adsorptive preconcentration of the drug on a
      hanging mercury drop electrode (HMDE), followed by tracing the voltammogram in a
      cathodic potential scan. The modes used are cyclic voltammetry (CV), cathodic
      stripping voltammetry (CSV) and differential pulse stripping voltammetry (DPSV).
      Amounts as low as 10 nM (10 ng x ml(-1)) (60 s preconcentration) by CSV and 0.5
      microM (190 ng x ml(-1)) (300 s) by DPSV can be determined accurately. The R.S.D.
      at the 1 x 10(-6) M level is 1.4%. The interference of some metal ions and the
      application of the method to analysis of urine, plasma and pharmaceutical
      formulations are described.

PMID- 9925337
TI  - Determination of rifampicin and its main metabolite in plasma and urine in
      presence of pyrazinamide and isoniazid by HPLC method.
AB  - A reversed phase HPLC method is described for the simultaneous estimation of
      rifampicin and its major metabolite desacetyl rifampicin, in the presence of
      isoniazid and pyrazinamide, in human plasma and urine. The assay involves simple
      liquid extraction of drug, metabolite and internal standard (rifapentine) from
      biological specimens and their subsequent separation on a C18 reversed phase
      column and single wavelength UV detection. In plasma as well as in urine samples,
      all the three compounds of interest eluted within 17 min. Using methanol-sodium
      phosphate buffer (pH 5.2; 0.01 M) (65:35, v/v) as mobile phase under isocratic
      conditions, it was established that isoniazid, pyrazinamide and ascorbic acid
      (added to prevent oxidative degradation of analytes) did not interfere with the
      analyte peaks. Recoveries (extraction efficiency) for drug were greater than 90%
      in both plasma and urine, whereas for metabolite the values were found to be 79
      and 86% in plasma and urine, respectively. The plasma and urine methods were
      precise (total coefficient of variation ranged from 5 to 23%) and accurate (-7 to
      5% of the nominal values) for both the analytes. Individual variance components,
      their estimates and their contribution to the total variance were also
      determined. Using the same method, unknown samples supplied by WHO were assayed
      and good correlations were obtained between the found and intended values. The
      method developed proved to be suitable for simultaneous estimation of rifampicin
      and desacetyl rifampicin in plasma and urine samples.

PMID- 9925338
TI  - Spectrophotometric and atomic absorption spectrometric determination of ramipril
      and perindopril through ternary complex formation with eosin and Cu(II).
AB  - Two sensitive, spectrophotometric and atomic absorption spectrometric procedures
      are developed for the determination of ramipril and perindopril. Both methods are
      based on the formation of a ternary complex, extractable with chloroform, between
      copper(II), eosin and the two cited drugs. Spectrophotometrically under the
      optimum condition, the ternary complexes showed an absorption maximum at 535 nm,
      with apparent molar absorptivities of 6.55 and 4.00 x 10(3) mol(-1) x cm(-1) and
      Sandell's sensitivities of 5.80 x 10(-2) and 1.04 x 10(-1) microg x cm(-2) for
      perindopril and ramipril, respectively. The solution of ternary complex obeyed
      Beer's law in concentration ranges 10-60 and 20-100 microg x ml(-1) for
      perindopril and ramipril, respectively. The proposed method was applied to the
      determination of the two cited drugs in pharmaceutical tablets. The atomic
      absorption spectrometric method, directly through the quantitative determination
      of copper content of the organic extract of the complex, was also investigated
      for the purpose of enhancing the sensitivity of the determination. The
      spectrophotometric and atomic absorption spectrometric procedures hold their
      accuracy and precision well when applied to the determination of ramipril and
      perindopril dosage forms.

PMID- 9925339
TI  - Determination of trace elements in a large series of spent peritoneal dialysis
      fluids by atomic absorption spectrometry.
AB  - An analytical procedure is reported for the determination of six elements in a
      large series of spent dialysis fluid samples. Determinations of aluminium,
      chromium, copper, manganese and iron were made by electrothermal atomic
      absorption spectrometry (ETAAS) with Zeeman background correction, while zinc was
      analysed by flame atomic absorption spectrometry (FAAS). Because of the complex
      matrix with high salt content and a high content of proteins, the measurement
      parameters were optimised for each particular element determined by ETAAS. The
      samples were collected in polyethylene eppendorf cups and stored in a freezer at 
      20 degrees C. When the elements were determined by ETAAS the standard addition
      method was applied in the calibration procedure. The sample (10 microl) was
      injected into a cuvette and careful drying and long ashing of samples at
      temperatures between 850 and 1000 degrees C performed. Triton X-100 was added
      before each determination to reduce the matrix effects of the proteins. Zinc was
      determined by FAAS in an air acetylene flame under the usual recommended
      procedure, calibrating with aqueous standards. The limits of detection (3sigma
      basis) were 1.0 microg x l(-1) for aluminium, 0.20 microg x l(-1) for chromium,
      0.40 microg x l(-1) for copper, 0.20 microg x l(-1) for manganese, 0.50 microg x
      l(-1) for iron and 5.0 microg x l(-1) for zinc. The reproducibility of the
      measurements for aluminium, copper, iron and zinc was better than +/-3.0%. It was
      worse for manganese and chromium (+/-6.0 and +/-12.0%, respectively), since these
      two elements were present in very low concentrations in all the samples analysed.

PMID- 9925340
TI  - LC/MS/MS analysis of vesnarinone and its principal metabolites in plasma and
      urine.
AB  - An LC/MS/MS assay was developed and successfully used to quantitate vesnarinone
      and its principal metabolites (OPC-8230, OPC-18136, and OPC-18137) in human
      plasma and urine. Samples were pre-treated with liquid-solid extraction followed
      by simultaneous monitoring of primary and daughter ions which were used for the
      identification and quantitation of the analytes on LC/MS/MS. This assay offers
      advantages of specificity, speed and greater sensitivity over the previously
      developed HPLC-UV assay. The lower limit of quantitation is 500 ng x ml(-1) for
      vesnarinone and 20 ng x ml(-1) for OPC-8230, OPC-18137, and OPC-18136 in plasma.
      Methodology is similar for the estimation of these analytes in urine with the
      lower limit of quantitation being 500 ng x ml(-1) for vesnarinone and 100 ng x
      ml(-1) for each metabolite. Ascorbic acid was added to stabilize the analytes
      from degradation. This LC/MS/MS method was developed to overcome many practical
      problems associated with the HPLC method. The LC/MS/MS method offers the
      flexibility of analyzing additional metabolites and changing the linearity range
      to accommodate the differences in linear range (200-10000 ng x ml(-1) for
      vesnarinone and 20-1000 for metabolites) for the analytes.

PMID- 9925341
TI  - High-performance frontal analysis for drug-protein binding study.
AB  - High-performance frontal analysis (HPFA) is a novel analytical method which
      enables simultaneous determination of total and unbound drug concentrations under
      drug-plasma protein binding condition. HPFA can be achieved using separation
      systems such as HPLC and CE. This paper deals with the principle and feature of
      HPFA method and its application to the stereoselective protein binding study.
      HPFA allows a simple analysis following direct sample injection, and does not
      suffer from undesirable drug adsorption on membrane nor leakage of bound drug
      through the membrane which are often encountered in conventional ultrafiltration
      and dialysis methods. HPFA can be easily incorporated into on-line HPLC system.
      By coupling HPFA with a chiral HPLC column, the unbound concentration of a
      racemic drug can be determined enantioselectively. The detection limit can be
      improved by coupling of HPFA with a preconcentration column. High-performance
      capillary electrophoresis/frontal analysis (HPCE/FA) enables to determine unbound
      concentrations enantioselectively with ultramicro injection volume, and is hence
      useful especially for the binding study of proteins which are scarce and
      difficult to obtain.

PMID- 9925342
TI  - Comparison of the complexation of fluoroquinolone antimicrobials with metal ions
      by nuclear magnetic resonance spectroscopy.
AB  - The complexation of fluoroquinolone antimicrobials with various metal ions have
      been studied in aqueous solution (pD 2.5, 37 degrees C) by 1H and 13C-NMR
      spectroscopy. The compounds examined are levofloxacin, ciprofloxacin and
      lomefloxacin. In each drug, new signals have appeared by the addition of Al3+,
      suggesting that the complexes are formed between the drug and Al3+ and that the
      ligand exchange is slow on the NMR time scale. Solution structure of the major
      species in the presence of 2.0 mol equiv of Al3+ has been proposed based on the
      large downfield shifts of some specific protons. Signals of both the coordinated
      and free drugs have shown slight broadening at 90 degrees C due to the enhanced
      rate in ligand dissociation process, though the coalescence phenomena are not
      observed even at this temperature. Thus, the complexes are supposed to be stable
      at the physiological condition. Titration experiments have revealed that the
      binding ability of levofloxacin toward Al3+ is much stronger than that of
      ciprofloxacin and lomefloxacin at pD 2.5. In contrast to the complexation with
      Al3+, the binding of these drugs with other metal ions such as Ca2+ and Mg2+ is
      much weaker; NMR signals have shown no appreciable downfield shift by the
      addition of Ca2+ and Mg2+. Based on these results, it is concluded that the
      fluoroquinolone antimicrobials examined in the present study at pD 2.5 exist as
      stable complexes in the presence of Al3+ and the absorptivity of the drugs on
      oral administration could be affected by Al3+.

PMID- 9925343
TI  - Evidence of defective cardiovascular regulation in insulin-dependent diabetic
      patients without clinical autonomic dysfunction.
AB  - (1) Autonomic dysfunction is a well recognised complication of diabetes mellitus
      and early detection may allow therapeutic manoeuvres to reduce the associated
      mortality and morbidity. We sought to identify early cardiovascular autonomic
      neuropathy using spectral analysis of heart rate and systolic blood pressure
      variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes
      mellitus (DM) and 30 matched control subjects were studied. In addition to
      standard tests of autonomic function, heart rate and systolic blood pressure
      variability were assessed using power spectral analysis. From the frequency
      domain analysis of systolic blood pressure and R-R interval, the overall gain of
      baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were
      normal in both groups. Total spectral power of R-R interval was reduced in the
      Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/-
      S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P <
      0.0001). Systolic blood pressure low-frequency power was increased in the
      diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low
      frequency/high frequency ratio for heart rate variability was significantly
      higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a
      relative sympathetic predominance. When absolute powers were expressed in
      normalised units, these differences persisted. There were significant reductions
      in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to
      controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and
      standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of
      cardiovascular variability detects autonomic dysfunction more frequently in Type
      1 DM patients than conventional tests, and is suggestive of an abnormality of
      parasympathetic function. The abnormality of baroreceptor-cardiac reflex
      sensitivity could be explained by this impairment of parasympathetic function and
      this may predispose to the development of hypertension and increase the risk of
      sudden cardiac death. Using spectral analysis methods may allow detection of
      early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to
      slow the progression.

PMID- 9925344
TI  - Effect of gemfibrozil on serum levels of prostacyclin and precursor fatty acids
      in hyperlipidemic patients with Type 2 diabetes.
AB  - Lipid-lowering fibrate drugs are known to affect the synthesis of fatty acids,
      which may alter the prostacyclin synthesis in diabetic patients. Therefore, the
      serum levels of precursor fatty acids and 6-keto-prostaglandin F1alpha (6-keto
      PGF1alpha) were determined in ten hyperlipidemic patients with Type 2 diabetes
      before and after administration of gemfibrozil (900 mg/day) for 3 months, in
      comparison with the results in seven non-diabetic hyperlipidemic patients.
      Gemfibrozil significantly reduced the serum concentration of dihomo-7-linolenic
      acid, total cholesterol and triglycerides, but did not affect the serum levels of
      arachidonic acid and 6-keto PGF1alpha in diabetic and non-diabetic patients.
      Thus, gemfibrozil did not affect the synthesis of prostacyclin in spite of the
      reduction of precursor fatty acids in diabetic and non-diabetic patients.

PMID- 9925345
TI  - The changes of lacunar state during a 5-year period in NIDDM.
AB  - With the increment of the aged, primary and secondary prevention of
      cerebrovascular disease in the Japanese diabetics are crucial problems. Early
      detection of asymptomatic infarction, not rare in diabetics, is important in the
      view of cost benefits. Little is known about the development and progression of
      asymptomatic infarction. We investigated the number of lacuna during a period of
      5 years in 51 non-insulin-dependent diabetes mellitus (NIDDM). At the initiation
      of this study, 22 patients were free from lacuna and another 29 patients had
      asymptomatic multiple lacunae. In the former patients, no risk factors were
      different between the 13 patients with still no lacuna and the nine patients with
      lacuna-developed after 5 years. In the latter patients, the 17 patients with
      worsening lacunar state had significantly higher systolic blood pressure, and a
      higher prevalence of macroalbuminuria than the 12 patients with no increment of
      lacuna. Multiple logistic regression analysis showed that macroalbuminuria after
      5 years was the only contributing factor to the increased lacuna. Therefore, in
      the NIDDM, macroalbuminuria induced an increase of lacuna in magnetic resonance
      imaging, although numbers of cases were relatively small. Prevention of the
      development of macroalbuminuria are essential to avoid the progression of
      asymptomatic lacuna.

PMID- 9925346
TI  - Decreased mitochondrial DNA content in peripheral blood precedes the development
      of non-insulin-dependent diabetes mellitus.
AB  - Qualitative changes in mitochondrial DNA (mtDNA), such as mutations and
      deletions, have been implicated in the pathogenesis of diabetes mellitus. In
      addition to the qualitative changes, mtDNA is subject to quantitative changes,
      and is vulnerable to oxidative stress, resulting in both qualitative and
      quantitative changes. This study was performed to investigate whether
      quantitative changes in mtDNA occur in non-insulin-dependent diabetes mellitus
      (NIDDM) patients and also in pre-diabetic subjects. MtDNA content from peripheral
      blood was measured by slot-blot analysis in 55 NIDDM patients and 29 age- and sex
      matched control subjects. We have also analysed the mtDNA copies by quantitative
      polymerase chain reaction (PCR) method in 23 pre-diabetic subjects who converted
      to diabetic in 2 years and 22 age- and sex-matched control subjects who remained
      non-diabetic. Mean mtDNA quantity measured by slot blot method was 35% lower in
      patients with NIDDM than in control subjects (12.3+/-8.1 vs. 19.1+/-8.2 AU/microg
      DNA; P < 0.05). MtDNA quantities did not correlate with age, body mass index,
      duration of diabetes or HbA1c levels. We have also found that the mtDNA copies in
      subjects who converted to diabetes in 2 years were lower than in controls even
      before the development of diabetes (102.8+/-41.5 vs. 137.8+/-67.7 copies/pg
      template DNA P < 0.05). Inverse correlations were noted between mtDNA content and
      baseline waist hip circumference ratio (WHR) (r = -0.31, P < 0.05), and fasting
      glucose level (r = - 0.35, P < 0.05), diastolic blood pressure (r = -0.36, P <
      0.05), and WHR (r = -0.40, P < 0.01) after development of diabetes. In
      conclusion, we demonstrate that the content of mtDNA decreases in peripheral
      blood of patients with NIDDM and the lower mtDNA levels precede the development
      of diabetes.

PMID- 9925347
TI  - Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type
      2 diabetics and patients with android type obesity.
AB  - The role of tumor necrosis factor-alpha in insulin resistance has been studied in
      59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy
      lean controls. Immunoreactive concentrations and bioactivity of serum tumor
      necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12
      months, five times per patients, by using ELISA and L929 cell cytotoxicity
      bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha
      concentrations and bioactivity have been found in both, the Type 2 diabetic and
      obese groups as compared to the healthy persons. Tumor necrosis factor-alpha
      concentrations and bioactivity have showed a significant positive linear
      correlation with the elevated basal serum C-peptide levels and body mass indexes
      in both groups of patients. According to these data the cytokine might play a
      role in insulin resistance in obesity as well in Type 2 diabetes.

PMID- 9925348
TI  - The use of Acarbose in Type 2 diabetic patients in secondary failure: effects on
      glycaemic control and diet induced thermogenesis.
AB  - Acarbose, an alpha-glucosidase inhibitor, delays the absorption of complex
      carbohydrates and sucrose, thereby lowering post-prandial blood glucose. In this
      study, we evaluated the effects of Acarbose on glycaemic control in Type 2
      diabetic patients in secondary oral hypoglycaemic agent failure. Due to its mode
      of action, we also used indirect calorimetry to examine its effects on energy
      expenditure (EE), diet induced thermogenesis (DIT) and respiratory quotient (RQ)
      after a standard breakfast (440 calories with 60 g carbohydrates). A total of 12
      patients (male/female, 8/4; age, 56+/-9 years; duration of diabetes 10.1+/-4.6
      years; body mass index (BMI) 29.6 + 2.7 kg/m2) with poor glycaemic control
      (HbA1c, 8.8+/-0.9%) completed 8 weeks treatment with Acarbose (100 mg). After
      treatment, HbAlc was lower compared to the baseline (8.8+/-0.9% vs. 8.0+/-0.9%; t
      = 2.7; P = 0.02). Acarbose acutely lowered post-prandial blood glucose and
      insulin area under the curve by a mean of 16.9% and 9.2%, respectively. Long term
      changes in HbA1c correlated strongly with acute changes in blood glucose area due
      to Acarbose administration (r = 0.87; P < 0.01). There was a significant effect
      of Acarbose on EE and DIT for the first 120 min post meal (F3,92 = 3.4; P = 0.03,
      F2,69 = 6.3; P = 0.008, respectively). After Acarbose treatment, RQ was lower at
      30 min compared to the baseline (0.86+/-0.04 before, and 0.83+/-0.05 after; t =
      2.8; P = 0.02). In conclusion, Acarbose improves glycaemic control and changes
      post-prandial energy expenditure of Type 2 diabetic patients in secondary
      failure. The magnitude of long term reduction in hyperglycaemia differs amongst
      individuals. This is largely due to intrinsic variations in patients' response to
      Acarbose rather than differences in medication compliance or dietary composition.

PMID- 9925349
TI  - Dietary profile of urban south Indians and its relations with glycaemic status.
AB  - This study was done to analyse the dietary profile of urban south Indian adults.
      It was also aimed to study, if the dietary profile influenced the glycaemic and
      anthropometric data. Dietary details were collected in a representative urban
      sample of 900 study subjects in the epidemiological survey for diabetes conducted
      in 1995 in the city of Madras. The details were collected by a 24-h recall
      method. All the dietary factors were similar in the non-diabetic (NGT) and newly
      diagnosed diabetic cases, but the values were lower in known diabetic cases due
      to dietary modifications (P < 0.001 for all compared to NGT and new diabetic
      cases). For further analysis, known diabetic cases were deleted and the rest were
      combined as one group. Men consumed higher calories (2066+/-437, range 1028-3662
      kcal) than women (1745+/-343, range 870-3260 kcal) (P < 0.01). Older persons
      consumed lower calories and percentages of the proximate principles in diet were
      proportionately lower. Higher calorie consumption was due to consumption of
      higher quantities of food and not any specific dietary factor. BMI, WHR, plasma
      glucose, serum cholesterol and triglycerides were not significantly influenced by
      the total calorie consumption. Calorie consumption was higher in persons engaged
      in strenuous physical activity. Total calories and proportionately the proximate
      principles of diet were less in the high income group. The similarity in diet in
      the non-diabetic and the newly diagnosed diabetic persons showed that the
      development of diabetes was probably not related to changes in dietary habits.
      Lower consumption of calories and carbohydrates by the known cases of diabetes
      was due to the dietary modifications introduced in the management of the disease.
      Lower calorie consumption in women and older people could be related to lower
      physical activity. This study shows a uniform dietary pattern among the different
      strata of society with minor variations based on age, gender and physical
      activity. No difference has been noted in dietary habits of the newly diagnosed
      diabetic subjects and the non-diabetic adults.

PMID- 9925350
TI  - Non-insulin-dependent diabetes in Kuwait: prevalence rates and associated risk
      factors.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a major clinical and public
      health problem in Kuwait. The objective of the study was to determine prevalence
      rates of NIDDM among a representative sample of the Kuwaiti adult population aged
      20 and older in two out of five governorates and identify the associated risk
      factors for the disease. A total of 3003 subjects (1105 men and 1898 women) were
      interviewed and examined by the research team during the period September 1995 to
      June 1996. A specially designed questionnaire was completed and the physical
      examination included height, weight and blood pressure measurements. Fasting
      blood samples were withdrawn, centrifuged immediately and refrigerated.
      Interpretation of oral glucose tolerance tests were based on the World Health
      Organisation diagnostic criteria for diabetes mellitus (1985). The denominator
      used for computing the prevalence was obtained from the 1995 Kuwait census. The
      overall prevalence of NIDDM in this study was found to be 14.8% (14.7% in men,
      14.8% in women). Diabetic subjects presented at a relatively young age,
      prevalence rate in the age group 20-39 was 5.7% (95% confidence interval, 4.4
      7.0) and in the age group 40-59 was 18.3% (95% confidence interval, 16.1-20.6).
      Obesity was found to be a significant risk factor, P < 0.001. The strong
      association of family history of NIDDM (adjusted odds ratio = 1.80, P < 0.001)
      suggests a genetic component. Hypertension was markedly associated with NIDDM and
      IGT (P < 0.001). With the demographic transition which already started among the
      Kuwaiti population and if the prevalence of NIDDM remains the same, aging of the
      population will contribute to even more upward trends in prevalence of abnormal
      glucose tolerance with its serious impact on morbidity and mortality among the
      Kuwaiti population. The strong association between hypertension and NIDDM may
      suggest a common approach to the prevention and control of these two conditions.

PMID- 9925351
TI  - A case-control study on risk factors for Type 1 diabetes in Taipei City.
AB  - To search for non-genetic risk factors for Type 1 diabetes among Chinese, a total
      of 117 Type 1 diabetes patients identified from the Taipei Type 1 Diabetes
      Registry and 193 frequency-matched controls with normal glucose tolerance were
      recruited. The controls were selected from classmates or colleagues of cases with
      similar distributions of age, sex, and parental and individual educational
      levels. Information on Type 1 diabetes risk factors was obtained through
      standardized interviews according to a structured questionnaire administered by
      two trained nurses. In the univariate analyses, the order of pregnancy of the
      study subject, the number of spontaneous and induced abortions reported by the
      mother before giving birth to the study subjects, the duration of breast-feeding
      and monthly family income were significantly associated with Type 1 diabetes in a
      dose-response manner. There was a U-shaped relationship with Type 1 diabetes for
      birth weight and paternal age at the conception of the study subjects. After
      further adjustment for multiple risk factors through logistic regression
      analysis, the biological gradient for pregnancy order, duration of breast
      feeding, and the U-shaped relationship for paternal age remained statistically
      significant.

PMID- 9925352
TI  - Troglitazone ameliorates insulin resistance in a diabetic patient with Prader
      Willi syndrome.
AB  - We report a patient with Prader-Willi syndrome (PWS) complicated by diabetes
      mellitus. PWS is a genetic disorder characterized by obesity, mental retardation
      and hypogonadism. Glucose intolerance in this syndrome is thought to be secondary
      to insulin resistance associated with morbid obesity. Therapy was directed
      primarily at decreasing insulin resistance and thereby improving glucose
      intolerance by the administration of troglitazone, which increases insulin
      sensitivity. Changes in glucose disposal rate assessed by euglycemic
      hyperinsulinemic clamp test were measured, as well as glucose and insulin
      responses to a 75 g-OGTT before and after troglitazone therapy. Glucose disposal
      rate increased by 36% and plasma glucose responses to 75 g-OGTT decreased by
      about 50% during 12 weeks of troglitazone therapy despite slight weight gain.
      Thus, troglitazone has beneficial effects on glycemic control by improving
      insulin sensitivity in patients with PWS complicated by diabetes mellitus.

PMID- 9925353
TI  - Differential alterations in left and right ventricular G-proteins in congestive
      heart failure due to myocardial infarction.
AB  - In order to examine the status of G-proteins in congestive heart failure due to
      myocardial infarction, the left coronary artery in rats was ligated and animals
      assessed after 4, 8 and 16 weeks. Sham-operated control and experimental animals
      were used for the preparation of membranes from the viable (uninfarcted) left and
      right ventricles. Adenylyl cyclase activities in the presence of pertussis toxin
      and cholera toxin were increased and decreased in left ventricles from all
      groups, respectively. On the other hand, adenylyl cyclase activities in 8 and 16
      week experimental right ventricles were unaltered in the presence of pertussis
      toxin and increased in the presence of cholera toxin. Depression of adenylyl
      cyclase activities in left ventricles from all groups as well as in the right
      ventricle at 4 weeks were not evident when enzyme activity was determined in the
      pertussis toxin-treated membranes in the absence or presence of Gpp(NH)p. Cholera
      toxin-catalyzed ADP ribosylation was decreased in left ventricles from all
      infarcted groups and increased in the right ventricles at 8 and 16 weeks whereas
      the pertussis toxin-catalyzed ADP ribosylation was increased in all experimental
      tissues except in the right ventricles at 8 and 16 weeks. G(s alpha)-protein
      content was decreased in the left ventricle at 16 weeks and increased in the
      right ventricles at 8 and 16 weeks of myocardial infarction. On the other hand,
      G(i alpha)-protein content was increased in left ventricles from all infarcted
      groups and the 4-week right ventricle but was unaltered in 8 and 16-week right
      ventricles. An increase in mRNA abundance for G(i alpha)-protein was seen in both
      left and right ventricles following myocardial infarction. A significant increase
      in mRNA level for G(s alpha)-protein was observed in all left ventricles and 8
      week right ventricle following the coronary occlusion. These results suggest that
      changes in Gs- and Gi-proteins in the failing heart due to myocardial infarction
      are chamber-specific and are dependent upon the stage of congestive heart
      failure.

PMID- 9925354
TI  - Effect of ischemic preconditioning on myocardial oxygen consumption during
      ischemia.
AB  - Ischemic preconditioning (IPC) in the heart may reduce myocardial energy demand.
      The present study was undertaken to examine changes in myocardial oxygen
      consumption (MVO2) during ischemia by IPC in Langendorff perfused rat hearts. We
      assessed MVO2 during ischemia from the measurement of mitochondrial cyt. aa3
      redox state by a two-wavelength reflectance spectrophotometry where T(1/2), the
      time from the onset of ischemia to the point for half reduction of cyt. aa3, was
      assumed to represent MVO2. The heart was preconditioned by three cycles of 5 min
      ischemia plus 5 min reperfusion and then subjected to 30 min global ischemia
      followed by reperfusion for 30 min. The T(1/2) was significantly longer in the
      preconditioned heart (30 +/- 6 s, n = 10) than the control heart (14 +/- 5 s, n =
      9, P<0.001), indicating a reduction of MVO2 during ischemic period by IPC. The
      prolongation of T(1/2) was evident after only one IPC episode. When the heart was
      perfused with high K+ solution to abolish MVO2 for contractions, we still found
      the prolongation of T1(1/2) in the preconditioned heart (116 +/- 12 s, n = 6)
      compared to the control heart (86 +/- 10 s, n = 6, P<0.01), suggesting that
      decrease in contractile activity may be, in part but not completely, responsible
      for the reduction of MVO2. In contrast, the prolongation of T(1/2) was completely
      abolished by administration of a NO synthase inhibitor N omega-nitro-L-arginine
      in the high K+ arrested heart, demonstrating involvement of NO in the reduction
      of MVO2, presumably by suppression of mitochondrial respiratory chain. In
      conclusion, IPC reduces MVO2 during ischemia. The reduction of MVO2 in the
      preconditioned heart may be accounted for by decreased contractile activity and
      by depression of respiratory chain by NO.

PMID- 9925355
TI  - Correlation of myocyte lengthening to chamber dilation in the spontaneously
      hypertensive heart failure (SHHF) rat.
AB  - Chronic congestive heart failure of various etiologies is characterized by
      progressive chamber dilation. Although myocyte lengthening is involved, it is not
      known if this cellular change can account for all of the chamber dilation. The
      controversy is due largely to technical limitations in collecting data on chamber
      circumference, myocyte length, and sarcomere length simultaneously. To address
      this issue, the contributions of myocyte and sarcomere lengthening to progressive
      chamber dilation in spontaneously hypertensive heart failure (SHHF) rats was
      examined using a new approach. Female SHHF rats (n=31) were examined at various
      time points between 2 months of age and the onset of end-stage heart failure (18
      months or older). A new method enabled simultaneous collection of data on myocyte
      length, sarcomere length, and chamber circumference using formalin-fixed tissue.
      Reliability of cellular measurements was confirmed with an alternate method. LV
      myocyte length increased linearly between 2 and 24 months of age due to series
      addition of sarcomeres. Myocyte length increased in direct proportion to chamber
      circumference during this period (r=0.93, P<0.001). Results suggest that myocyte
      lengthening alone can account for chamber dilation in the progression to heart
      failure. Excessive myocyte lengthening is a slow, progressive change that begins
      long before clinical signs and symptoms of heart failure appear in this model of
      hypertension and failure. Since myocyte remodeling in hypertensive humans with
      and without failure is known to resemble that in SHHF rats, these data should
      provide important insight into chamber dilation and the progression of heart
      failure in humans.

PMID- 9925356
TI  - Ventricular fibrillation-induced intracellular Ca2+ overload causes failed
      electrical defibrillation and post-shock reinitiation of fibrillation.
AB  - Despite high efficacy, electrical defibrillation shocks can fail or ventricular
      fibrillation (VF) is reinitiated after the application of the initial shock. The
      goal of this study was to determine whether [Ca2+]i overload, induced by VF
      itself, can cause failed electrical defibrillation and post-shock reinitiation of
      VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by
      indo-1 fluorescence) and defibrillation energies (assessed by a modified
      implantable cardioverter defibrillator) in intact perfused rat hearts during
      pacing-induced sustained VF (10 min) in the absence of ischemia. We found that
      increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the
      defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and
      also increased the total defibrillation energy (TDE) required for stabilization
      of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition,
      both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05).
      Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit
      [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks
      led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In
      contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i
      overload after initially successful shocks were often followed by synchronized
      spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In
      conclusion, the present study showed for the first time that VF-induced [Ca2+]i
      overload can cause failed electrical defibrillation and post-shock reinitiation
      of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a
      crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.

PMID- 9925357
TI  - The thrombin receptor elevates intracellular calcium in adult rat ventricular
      myocytes.
AB  - While there is evidence that thrombin receptor activation leads to contractile
      dysfunction and induces arrhythmias in ischemic/reperfused cardiac tissue,
      thrombin is variably reported to modulate intracellular calcium in
      cardiomyocytes. The present study demonstrates that thrombin receptor activation
      leads to a rise in intracellular calcium in adult ventricular myocytes and serves
      to reconcile previous discrepant findings. The thrombin receptor-derived agonist
      peptide (SFLLRN, a portion of the tethered ligand created by thrombin's
      proteolytic actions) increases cytosolic calcium and twitch amplitude in
      cardiomyocytes isolated from adult ventricles. The truncated control peptide
      FLLRN has no effect, establishing that the response to SFLLRN results from a
      specific agonist peptide-receptor interaction. However, the response to SFLLRN
      occurs only at high agonist peptide concentrations and thrombin itself is
      inactive. This result is not compatible with an action of SFLLRN at a distinct
      protease-activated receptor (PAR-2; which is activated by SFLLRN, but not by
      thrombin), since SLIGRL (a ligand which is selective for PAR-2, but not the
      thrombin receptor) has no effect. Rather, the enzyme-based cell isolation
      procedure may partially cleave the thrombin receptor and influence cell
      responses, since concentrations of SFLLRN which are sub-threshold in
      enzymatically disaggregated myocytes significantly increase the force of
      isometric contraction of intact rat papillary muscles. These studies provide the
      first evidence that thrombin receptor activation leads to a change in
      intracellular calcium and a positive inotropic response in adult ventricular
      myocardium.

PMID- 9925358
TI  - The PKC activator PMA preconditions rabbit heart in the presence of adenosine
      receptor blockade: is 5'-nucleotidase important?
AB  - While there is good evidence that both protein kinase C (PKC) and adenosine are
      involved in ischemic preconditioning, their sequence in the intracellular
      signaling cascade is in dispute. One hypothesis proposes that PKC activation
      causes release of adenosine which then protects the heart, while the other
      proposes that adenosine stimulates PKC which in turn causes protection.
      Accordingly, we studied the effects of specified sequences of pharmacologic
      triggers and blockers on the infarct-sparing effect of a preconditioning
      protocol. The combination of the adenosine receptor agonist R(-)N6-(2
      phenylisopropyl) adenosine (PIA) and the PKC blocker chelerythrine would be
      protective only if the first hypothesis were correct. On the other hand, the
      combination of the adenosine receptor blocker 8-(p-sulfophenyl) theophylline
      (SPT) and a PKC activator would be protective only if the second hypothesis were
      correct. Isolated, Krebs-perfused rabbit hearts experienced 30 min of regional
      ischemia and 2 h of reperfusion. Infarct size was quantitated by
      triphenyltetrazolium chloride staining. In untreated control hearts, 30.0 +/-
      2.7% of the risk zone infarcted. Fifty nmol/l PIA for 20 min starting 10 min
      prior to ischemia resulted in only 8.4 +/- 1.9% infarction (P<0.01), while the
      combination of PIA and 5 micromol/l chelerythrine resulted in large infarcts of
      27.8 +/- 3.2%. This attenuation of the protective effect continued to be observed
      even when the PIA infusion was continued to the end of the reperfusion period.
      Conversely, 0.2 nmol of the PKC activator phorbol 12-myristate 13-acetate (PMA)
      infused during the 10-min interval prior to ischemia protected the hearts (6.5 +/
      1.3% infarction, P<0.01 v control). And protection persisted when PMA-treated
      hearts were also exposed to 100 microM SPT for 35 min starting 5 min prior to
      ischemia (9.5 +/- 1.9% infarction, P<0.01 v control). When PKC activation by the
      PKC-coupled agonist phenylephrine was continued to the end of ischemia and
      adenosine blockade was extended throughout the reperfusion period by prolonged
      infusion of SPT, protection was unaffected. The administration of either SPT or
      chelerythrine alone did not confer any protection (32.5 +/- 3.3 and 34.0 +/- 3.2%
      infarction, respectively). Thus, because the combination of PKC activation and
      adenosine receptor blockade was protective while that of adenosine receptor
      agonist and PKC blockade was not, adenosine receptors must be upstream of PKC in
      preconditioning.

PMID- 9925359
TI  - Whole body heat shock fails to protect mouse heart against ischemia/reperfusion
      injury: role of 72 kDa heat shock protein and antioxidant enzymes.
AB  - The transgenic mice overexpressing heat shock protein 72 (HSP72) or antioxidants
      have been reported to be more resistant to myocardial ischemia/reperfusion
      injury. However, it remains unknown whether whole body heat stress (HS) which may
      induce HSP72 or endogenous antioxidants affords similar protection in the mouse
      heart. Adult male mice were treated with either HS (42 degrees C for 15 min) or
      anesthesia only (SC) against a group of non-stressed controls (NC). At 6 or 24 h
      later, the hearts were excised and perfused at a constant pressure of 55 mmHg in
      Langendorff mode. Following 30 min equilibration, hearts were subjected to 20 min
      of global ischemia and 30 min reperfusion (37 degrees C). Ventricular force was
      measured by a force-displacement transducer attached to the apex. Leakage of
      intracellular enzymes (CK, LDH) was measured in coronary efflux. Infarct size was
      determined by tetrazolium staining. The results showed that no significant
      differences between HS, SC, and NC groups in ventricular contractile function, CK
      and LDH release, or infarct size were observed at either time window. HS enhanced
      the expression of HSP72 in mouse hearts by two- to three-fold, whereas
      antioxidant enzyme activities (catalase and MnSOD) did not change significantly.
      We conclude that HS does not precondition the isolated perfused mice hearts
      against ischemia/reperfusion injury, despite induction of HSP72.

PMID- 9925360
TI  - Complications associated with rapid caffeine application to cardiac myocytes that
      are not voltage clamped.
AB  - The rapid application of caffeine to cardiac myocytes is commonly used to assess
      changes in the Ca2+ content of the sarcoplasmic reticulum (SR) and to study other
      parameters of intracellular Ca2+ regulation. Here we examined the effects of
      rapid caffeine application on membrane potential, intracellular Ca2+, and cell
      shortening in ventricular myocytes (rat, rabbit, guinea pig, dog) and atrial
      myocytes (rabbit) that were not voltage clamped. Conditioning pacing was used to
      achieve a steady-state level of SR Ca2+ loading prior to caffeine (10 mM)
      application. Caffeine transiently depolarized myocytes as expected from
      activation of forward Na+-Ca2+ exchange. However, we also found in each species
      (50% rat, 36% rabbit ventricular, 53% rabbit atrial, 56% guinea pig, 31% dog)
      that the caffeine-induced depolarization could also trigger an action potential.
      Caffeine-triggered potentials were completely blocked by thapsigargin (1 microM).
      The Ca2+ transient and contraction that accompanied caffeine-triggered action
      potentials had a larger magnitude and slower rate of decline (or relaxation) than
      occurred during caffeine-induced subthreshold depolarizations. Thus, the use of
      rapid caffeine application to study SR function and [Ca2+]i regulation in
      myocytes that are not voltage clamped can yield erroneous results.

PMID- 9925361
TI  - Sustained left ansae subclaviae stimulation for a 5-hour period inhibits cesium
      induced ventricular arrhythmogenesis in rabbits.
AB  - The acute stimulation of the left ansae subclaviae (LAS) augments cesium chloride
      (Cs)- induced early afterdepolarizations (EADs) and ventricular arrhythmias.
      However, the effect of sustained cardiac sympathetic nerve stimulation on Cs
      induced arrhythmogenesis remains to be elucidated. Three protocols were used. In
      protocol A, seven rabbits received continuous LAS stimulation for 5 h (study
      group), and were then given bolus injections of Cs at 5-min intervals (initial
      dose 1.5 mmol/kg, followed by repetitive doses 1 mmol/kg). Another eight rabbits
      received the same dose of Cs after a 5-h observation period without LAS
      stimulation (control group). The effects of 2 h of LAS stimulation were also
      assessed in five rabbits of each group. In protocol B, a bolus injection of Cs (1
      mmol/kg) was administered during atrial pacing (cycle length: 250 ms) after a 5-h
      period with (study group, n = 5) or without (control group, n = 5) LAS
      stimulation, and the amplitude of Cs-induced EADs was measured. In protocol C, a
      bolus injection of isoproterenol (0.05 mg/kg) was given after a 5-h period with
      (study group, n = 5) or without (control group, n = 5) LAS stimulation to assess
      the sensitivity to beta-adrenergic stimulation. In protocol A, the cumulative
      doses of Cs required for the induction of ventricular tachycardia (VT) and
      fibrillation (VF) were significantly greater in the study group than in the
      control group (4.4 +/- 0.1 v 2.8 +/- 0.3 mmol/kg for VT, P<0.05; 5.8 +/- 0.3 v
      4.1 +/- 0.4 mmol/kg for VF, P<0.05). However, 2 h of LAS stimulation did not
      influence the cumulative doses of Cs required for the induction of VT and VF. In
      protocol B, the amplitude of Cs-induced EADs was significantly lower in the study
      group than in the control group. In protocol C, the increase in rate-pressure
      product by isoproterenol was significantly less in study than in control groups
      (3492 +/- 612 v 6504 +/- 829, P<0.05). These results suggest that sustained LAS
      stimulation exerts a protective effect against Cs-induced arrhythmogenesis in the
      rabbit heart, which may be partially explained by desensitization to the beta
      adrenergic stimulation.

PMID- 9925362
TI  - Cyclic stretch down-regulates calcium transporter gene expression in neonatal rat
      ventricular myocytes.
AB  - Abnormal intracellular Ca2+ handling in hypertrophied and failing hearts is
      partly due to changes in Ca2+ transporter gene expression, but the mechanisms
      responsible for these alterations remain largely unknown. We previously showed
      that intrinsic mechanical load (i.e. spontaneous contractile activity) induced
      myocyte hypertrophy, and down-regulated SR Ca2+ ATPase (SERCA2) gene expression
      in cultured neonatal rat ventricular myocytes (NRVM). In the present study, we
      examined whether extrinsic mechanical load (i.e. cyclic stretch) also induced
      NRVM hypertrophy, and led to down-regulation of SERCA2 and other Ca2+ transporter
      genes which have been associated with cardiac hypertrophy and failure in vivo.
      NRVM were maintained in serum-free culture medium under control conditions, or
      subjected to cyclic mechanical deformation (1.0 Hz, 20% maximal strain, 48 h).
      Under these conditions, cyclic stretch induced NRVM hypertrophy, as evidenced by
      significant increases in total protein/DNA ratio, myosin heavy chain (MHC)
      content, and atrial natriuretic factor (ANF) secretion. Cyclic stretch also
      induced the MHC isoenzyme "switch" which is characteristic of hemodynamic
      overload of the rat heart in vivo. Cyclic stretch significantly down-regulated
      SERCA2 and ryanodine receptor (RyR) mRNA and protein levels, while simultaneously
      increasing ANF mRNA. In contrast, Na+-Ca2+ exchanger and phospholamban mRNA
      levels were unaffected. Load-dependent SERCA2 and RyR down-regulation was
      independent of Ca2+ influx via voltage-gated, L-type Ca2+ channels, as cyclic
      stretch down-regulated SERCA2 and RyR mRNA levels in both control and verapamil
      treated NRVM. These results indicate that extrinsic mechanical load (in the
      absence of other exogenous stimuli) induces NRVM hypertrophy and causes down
      regulation of Ca2+ transporter gene expression. This in vitro model system should
      prove useful to dissect the intracellular signaling pathways responsible for
      transducing this phenotype during cardiac hypertrophy and heart failure in vivo.

PMID- 9925363
TI  - Molecular cloning of rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein).
AB  - Rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein), a membrane-bound enzyme
      requiring millimolar concentrations of Ca2+ or Mg2+ for maximal hydrolysis of
      ATP, has been purified to apparent homogeneity. Tryptic digestion and amino acid
      sequencing was used to design an oligonucleotide probe for screening a rat heart
      cDNA library; this produced a partial cDNA clone (pND2.1), and sequencing of a
      400 base pair portion revealed a 100% homology to human platelet CD36. Northern
      blotting with pND2.1 detected a 3.1 kb transcript in rat heart but not in other
      tissues. Interspecies expression analysis (cardiac tissue total RNA blot probed
      with pND2.1) detected a approximately 2.0 kb transcript in canine, rabbit and
      porcine heart, whereas transcripts of a 4.1 kb, approximately 3.0 kb and 2.1 kb
      were observed in human cardiac tissue. A rat genomic DNA Southern blot, probed
      with pND2.1, indicated that there was a single copy of the gene in the rat
      genome. Expression of the pND2.1 cDNA in E. coli produced an 89 kDa polypeptide
      recognized by anti-human CD36 antibody but not by anti-rat Ca2+/Mg2+ ectoATPase
      antibody. It is concluded that rat cardiac Ca2+/Mg2+ ectoATPase is tightly
      associated with a protein highly homologous to the adhesion molecule CD36.

PMID- 9925364
TI  - Distinct molecular phenotypes in murine cardiac muscle development, growth, and
      hypertrophy.
AB  - The onset of cardiac hypertrophy is associated with characteristic changes in
      myocardial gene expression that are thought to recapitulate a developmental gene
      program. We report here the first gene expression profile of the murine
      myocardium, using a rapid method of quantitative expression analysis based on
      real-time analytical RT-PCR. This assay was used to measure expression levels of
      29 genes in (1) late stage development as represented by day 1 neonatal
      ventricles, (2) normal cardiac growth in 3 and 18 month old mice, and (3) cardiac
      hypertrophy following pressure overload by aortic constriction. For males and
      females normal growth is not associated with differential expression although
      there is elevated expression of skeletal and smooth muscle actin mRNA's in males
      compared to females. Using normal adult ventricles as a reference, there are many
      qualitative and quantitative differences between the day 1 neonatal myocardium
      and experimental cardiac hypertrophy. These data suggest that the response to POL
      involves a subset of re-expressed developmental genes together with altered
      expression of genes not necessarily associated with cardiac development.

PMID- 9925365
TI  - Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury
      in transgenic mice.
AB  - Generation of free radicals upon reperfusion has been cited as one of the major
      causes of ischaemia/reperfusion injury. The following series of experiments was
      designed to study the effect of manganese superoxide dismutase (MnSOD)
      overexpression in transgenic mice on ischemia/reperfusion injury. A species of
      1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was
      detected in the hearts of transgenic mice with no changes in the other
      antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an
      increased labeling of MnSOD mainly in the heart mitochondria of the transgenic
      mice. When these hearts were perfused as Langendorff preparations for 45 min
      after 35 min of global ischemia, the functional recovery of the hearts, expressed
      as heart rate x left ventricular developed pressure, was 52 +/- 4% in the
      transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This
      protection was accompanied by a significant decrease in lactate dehydrogenase
      release from the transgenic hearts. Overexpression of MnSOD limited the infarct
      size in vivo in a left coronary artery ligation model. Our results demonstrate
      that overexpression of MnSOD renders the heart more resistant to
      ischemia/reperfusion injury.

PMID- 9925366
TI  - Vascular remodeling and altered protein expression during growth of coronary
      collateral arteries.
AB  - The cellular mechanism of growth of coronary collateral vessels (adaptive
      arteriogenesis) is still poorly understood. To define a possible role of an
      altered expression pattern of cellular and matrix proteins in this process we
      implanted a constricting device around the left circumflex artery in 25 canine
      hearts and sacrificed the animals at the time of initiation (3 weeks), high
      activity (6 weeks) and discontinuation (8 weeks) of vessel growth. Methods were
      electron microscopy, labeling with Ki-67, the TUNEL method and immunofluorescence
      with confocal laser microscopy. As described earlier, the collateral vessels
      increased in wall thickness by the formation of a neointima without luminal
      narrowing. We report here for the first time that extensive vascular remodeling
      including migration, proliferation and apoptosis in all cell types takes place
      during the growth phase but not in more mature vessels. The most obvious
      difference with normal vessels is the reiteration of an embryonal expression
      pattern in smooth muscle cells of the neointima which includes a significant
      reduction of desmin and alpha-smooth muscle actin, calponin and vinculin.
      Fibronectin as a promoter of migration and adhesion was abundant, its antagonist
      tenascin and chondroitin sulfate showed patchy localization. A completely new
      finding in arteriogenesis is the involvement of mast cells releasing histamine
      and serotonin and probably cytokines. Vascular protein expression returned to
      almost normal at 8 weeks indicating cessation of remodeling. We conclude that in
      collateral vessel development an altered cellular and matrix protein expression
      is involved in a drastic case of positive vascular remodeling finally resulting
      in mature vessels 20-fold increased in size which are capable of maintaining the
      functional and structural integrity of the myocardium at risk.

PMID- 9925367
TI  - Regulation of intracellular free Mg2+ concentration in isolated rat hearts via
      beta-adrenergic and muscarinic receptors.
AB  - Regulation of the intracellular free magnesium concentration ([Mg2+]i) was
      investigated in isolated rat hearts, using 31P-nuclear magnetic resonance (31P
      NMR). [Mg2+]i was found to be slowly and significantly decreased during prolonged
      application of isoproterenol (ISO) through beta-adrenergic receptor stimulation,
      and restored by subsequent washouts. The ISO-induced decrease in [Mg2+]i was
      antagonized by addition of a muscarinic receptor agonist, carbachol (CCh). In the
      presence of atropine, CCh did not exert this effect. A water-soluble forskolin
      derivative, NKH477, which directly activates adenylate cyclase, also caused a
      decrease in [Mg2+]i, which could be antagonized by CCh, but a greater
      concentration was required as compared to the ISO case. The manner of [Mg2+]i
      regulation mimicked those noted for the action potential duration and the Ca2+
      channel current, in which cAMP is known to act as a second messenger. Even in the
      presence of a Ca2+ channel blocker, verapamil, [Mg2+]i was reversibly decreased
      by ISO. Changes in the intracellular ATP concentration demonstrated any clear
      correlation with changes in [Mg2+]i. These results suggest that [Mg2+]i can be
      controlled by a balance of sympathetic and parasympathetic activities. cAMP may
      play a key role in the [Mg2+]i regulation via beta-adrenergic and muscarinic
      receptors, although some other metabolic pathways also appear to be involved.
      Hormonally induced changes in [Mg2+]i have possible clinical significance.

PMID- 9925368
TI  - Carnitine promotes heat shock protein synthesis in adriamycin-induced
      cardiomyopathy in a neonatal rat experimental model.
AB  - In order to evaluate carnitine protective strategy and its relationship with heat
      shock protein induction, female Sprague-Dawley neonatal rats, body weight 40 g,
      were randomized into four groups: control, adriamycin, carnitine and carnitine
      adriamycin. Adriamycin was injected i.v. at a dose of 27 mg/kg (0.1 ml).
      Carnitine was administered i.v. (20 mg/0.1 ml) before each subdose of adriamycin
      and then per os (180 mg/kg) daily for 12 weeks. Body weight was recorded weekly.
      Ventricular wall thickness and cellular damage percentage were morphometrically
      and ultrastructurally determined, respectively. The determinations were realized
      monthly until the third month after treatment. The heat shock protein 25 content
      in the supernatant of the homogenized heart tissue was determined by Western blot
      analysis. Eight and 12 weeks after treatment, body weight and ventricular wall
      thickness decreased much more in adriamycin groups than in control and carnitine
      ones. At the same time, electron microscopic analysis of adriamycin left
      ventricular wall samples showed loss of myofibrils, swollen mitochondria and
      vacuoles. Carnitine-adriamycin treated rats resemble control groups more than
      adriamycin treated samples. Moreover, de-novo synthesis of heat shock protein was
      three times more induced in carnitine-adriamycin rats than in adriamycin ones.
      Carnitine may enhance the cell-protecting mechanism based on an induction of
      shock protein, and this first cellular response could reduce the severity of late
      adriamycin-cardiomiopathy.

PMID- 9925369
TI  - Pyruvate potentiates beta-adrenergic inotropism of stunned guinea-pig myocardium.
AB  - This study tested the hypotheses that the sensitivity of stunned myocardium to
      beta-adrenergic stimulation is diminished, and that metabolic intervention with
      pyruvate can restore beta-adrenergic responsiveness to pre-ischemic levels.
      Isolated working guinea-pig hearts metabolizing 10 mM glucose were stunned by 45
      min of low flow ischemia, and pyruvate and/or isoproterenol treatments were
      initiated 15 and 30 min after reperfusion, respectively. The dose: response for
      cardiac power from 0.1-100 nM isoproterenol was significantly shifted to the
      right in stunned hearts: EC50 (nm) increased from 0.3 +/- 0.06 to 5.2 +/- 1.86.
      Pyruvate (5 mM) largely restored isoproterenol responsiveness of stunned
      myocardium, lowering EC50 to 1.1 +/- 0.34 nM. Maximum power was similar in each
      group. Additional stunned hearts were treated with intermediate (2 nM) or high
      (30 nM) isoproterenol concentrations with or without pyruvate. Combining
      treatments produced a significant interaction at the low dose of isoproterenol,
      increasing cardiac power (mJ x min(-1) x g(-1)) to 149 +/- 20, twice the sum of
      the individual treatments (2 nM isoproterenol: 34 +/- 11; pyruvate: 33 +/- 8).
      Cyclic AMP content was unaltered by isoproterenol or pyruvate alone but was
      increased 41% by the combination. Power was maximized by 30 nM isoproterenol,
      which tripled cyclic AMP content; pyruvate did not augment these responses, but
      lessened the isoproterenol-induced decline in cytosolic phosphorylation
      potential. CONCLUSIONS: Beta-adrenergic inotropism is attenuated in stunned
      myocardium, although the maximal response is unchanged. Pyruvate potentiated the
      effects of sub-maximal doses of isoproterenol without depleting cellular energy
      reserves further, and attenuated energy depletion by high doses of isoproterenol.
      Pyruvate may allow restoration of contractile performance with lower,
      energetically less costly doses of beta-adrenergic agents.

PMID- 9925370
TI  - Decreased susceptibility of contractile function to hypoxia/reoxygenation in
      chronic infarcted rat hearts.
AB  - Cardiac hypertrophy is associated with modifications in Ca2+ transport processes,
      enzymes of energy metabolism and antioxidant capacity. It is unknown whether
      these changes occur in infarct-induced hypertrophy with regard to an altered
      susceptibility to ischemia/reperfusion injury. We examined changes in
      sarcoplasmic reticulum (SR) Ca2+ transport, creatine kinase (CK) system, and the
      antioxidant enzymes glutathionperoxidase (GSH-Px) and superoxide dismutase (SOD)
      in rats 6 weeks after infarction due to coronary ligation (MI). Phenotypic
      modifications v sham operation (SHAM) were related to the contractile response of
      hypertrophied papillary muscle to hypoxia/reoxygenation for 30 min each. Under
      aerobic conditions we observed in MI v SHAM: decreases in isometric contraction
      and relaxation rate, a reduced Vmax-equivalent of sarcomeric shortening, a faster
      twitch-to-twitch decay of post-rest potentiation (PRC) which correlated closely
      to the decrease in SR Ca2+ uptake (-25%), a decrease in CK activity (-20%),
      reduced CK-MI and CK-MM, increased CK-MB and CK-BB, and enhanced activities of
      SOD (40%) and GSH-Px (50%). During hypoxia, an initial increase in peak force
      (PF) was followed by a slower PF decline in MI v SHAM. Reoxygenation caused a
      recovery of PF to approximately 30% in both groups; rates of contraction and
      relaxation recovered better in MI. In SHAM but not MI, twitch-to-twitch decay of
      PRC was accelerated after reoxygenation v aerobic control. The results suggest
      that adaptive changes in SR Ca2+ handling, CK isoenzymes and antioxidant enzymes
      may contribute to higher resistance against reduced oxygen supply and
      reoxygenation in hypertrophy due to MI.

PMID- 9925371
TI  - Angiotensin AT1 receptor inhibition in pacing induced heart failure: effects on
      left ventricular myocardial collagen content and composition.
AB  - The progression of left ventricular (LV) dilation with congestive heart failure
      (CHF) is associated with an increased incidence of morbidity and mortality. The
      LV myocardial extracellular matrix has been implicated to play an important role
      in maintaining chamber shape and myocyte alignment. While angiotensin II AT1
      receptor (Ang AT1) receptor activation has been demonstrated to contribute to
      increased vascular resistance with the CHF, whether activation of the myocardial
      Ang AT1 receptor system contributes to LV dilation and myocardial collagen
      remodelling with CHF remains unclear. The goal of this study was to examine the
      effects of Ang AT1 receptor inhibition on LV geometry and myocardial collagen
      content and structure with the development of pacing CHF. Pigs (25 kg) were
      instrumented in order to measure LV function in the conscious state and were
      assigned to one of three groups: (1) Pacing CHF: rapid atrial pacing (240 bpm)
      for 3 weeks (n = 7); (2) Pacing CHF and Ang AT1 Block: concomitant Ang AT1
      receptor blockade (valsartan, Novartis, Basel 60 mg/day) and rapid pacing (n =
      7); (3) sham controls (n = 7). The Ang AT1 receptor antagonist was delivered by
      osmotic minipump and this dose has been demonstrated previously to significantly
      blunt the Ang-II pressor response. LV pump function and geometry was assessed by
      echocardiography and LV myocardial collagen content by computer assisted
      histomorphometry and biochemistry. In the pacing CHF group, LV fractional
      shortening was reduced (17 +/- 2 v 45 +/- 1%) and LV end-diastolic dimension
      increased (5.91 +/- 0.09 v 3.75 +/- 0.07 cm) compared to controls (P<0.05). In
      the pacing CHF and Ang AT1 blockade group, LV pump function and dimensions were
      similar to untreated pacing CHF values. The relative content of LV myocardial
      fibrillar collagen was reduced with pacing CHF (7.6 +/- 0.4 v 11.3 +/- 0.6%)
      compared to controls (P<0.05), and was similarly reduced in the pacing CHF and
      Ang AT1 receptor blockade group (8.3 +/- 0.4%, P<0.05). LV myocardial
      hydroxyproline was reduced with pacing CHF compared to controls (2.35 +/- 0.21 v
      2.89 +/- 0.42 mg/gdwt, P<0.05). While reduced with pacing CHF and Ang AT1
      receptor blockade (2.54 +/- 0.25 mg/gdwt), this was not significantly different
      from controls (P=0.23). Ang AT1 receptor inhibition in this model of CHF did not
      appear to favorably affect the degree of LV dilation and myocardial collagen
      structure. These results suggest that activation of the myocardial Ang AT1
      receptor may not significantly contribute to LV remodelling with pacing CHF.

PMID- 9925372
TI  - Characterization of a novel gene encoding zinc finger domains identified from
      expressed sequence tags (ESTs) of a human heart cDNA database.
AB  - Seven types of zinc finger protein (ZFP) genes based on the combinations of
      cysteine and histidine residues were found in a human heart cDNA database. Here
      we report the isolation of 360 cDNA clones encoding putative ZFPs. Of these, 154
      (42.8%) represent C2H2-type ZFPs, 101 (28.1%) represent C2C2-type, five (1.4%)
      represent C2HC-type, 71 (19.7%) represent C2HC4C(HD)-type, three (0.8%) represent
      C3H-type, eight (2.2%) represent C3HC4-type and 18 (0.5%) represent combination
      type (genes containing more than one type of zinc finger). Among these 360 ZFPs,
      a novel ZFP cDNA named HFHZ (human fetal heart ZFP) with sequence homology to a
      Kruppel-associated box (KRAB) was identified. Sequencing the full-length of this
      cDNA clone identified an open reading frame of 711 bp that encodes a 237 amino
      acid protein with a predicted molecular weight of 27.7 kDa. Sequence analysis
      indicated that HFHZ contained a truncated KRAB box at the N-terminus and two C2H2
      zinc fingers at the C-terminus. The transcript of HFHZ is highly expressed in
      fetal heart and moderately expressed in fetal brain but not expressed in fetal
      liver as revealed by reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis suggesting that HFHZ is not expressed ubiquitously. The 3.3-fold higher
      expression in the fetal heart than in the adult heart suggests that HFHZ mRNA is
      downregulated in the process of development. In addition, the relatively high
      expression (1.9-fold) of HFHZ observed in the hypertrophic as compared to the
      normal adult heart suggests that this fetal gene is reactivated in response to
      hypertrophic stimuli. Chromosomal localization by in situ hybridization revealed
      that this gene is in 19q13.1, a region containing genes involved in both cell
      cycle and developmental regulation.

PMID- 9925373
TI  - Regulation of vascular smooth muscle migration by mitogen-activated protein
      kinase and calcium/calmodulin-dependent protein kinase II signaling pathways.
AB  - Platelet-derived growth factor BB (PDGF BB) activation of the mitogen-activated
      protein kinases (MAPK), ERK1 and ERK2, has been shown to be necessary for mitogen
      stimulated proliferation, but its role in regulating cell migration and its
      relationship to other chemotactic signaling events, such as CamKII activation,
      has not been defined. Using a modified Boyden chamber apparatus, we tested the
      effects of a selective inhibitor of the upstream activator of ERK1/2, MEK1, on
      PDGF-stimulated rat aortic vascular smooth muscle cells (VSMCs) alone and in
      combination with KN62, a selective inhibitor of CamKII. The MEK1 inhibitor,
      PD98059, caused a dose-dependent reduction in ERK2 activity that paralleled a
      decrease in migration up to 60%. This inhibition of migration was similar to that
      seen with KN62 and the combined effects of both inhibitors were non-additive.
      Although KN62 did not affect ERK2 activity in response to PDGF, PD98059 markedly
      inhibited PDGF-stimulated CamKII activity, suggesting that activation of CamKII
      by PDGF was dependent on ERK activity and that the effects of ERK inhibition on
      migration may be mediated through its ability to inhibit CamKII activity. To
      directly test this, VSMCs were infected with a recombinant adenovirus expressing
      constitutively activated CamKII. Infection reversed the inhibitory effects of
      KN62 on migration, but had no effect on the inhibition of migration seen with
      PD98059. These results suggest that while MAPK may act upstream of CamKII to
      control its activation in response to PDGF, it also regulates migration
      independently of CamKII activation.

PMID- 9925374
TI  - Muscle unloading induces slow to fast transitions in myofibrillar but not
      mitochondrial properties. Relevance to skeletal muscle abnormalities in heart
      failure.
AB  - Muscle deconditioning is a common observation in patients with congestive heart
      failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or
      prolonged bed rest. To gain further insight into metabolic and mechanical
      properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal
      muscles, we induced experimental muscle deconditioning by hindlimb suspension
      (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound
      muscle atrophy, increased proportion of fast type II fibers as well as fast
      myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned
      fiber bundles of soleus muscle directed towards the fast muscle phenotype.
      Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the
      LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic
      profile. Creatine kinase (CK) and myokinase activities were increased in HS
      soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in
      soleus, with no change in EDL. However, oxygen consumption rate assessed in situ
      in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g
      dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as
      well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved
      in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial
      respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS
      soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/-
      10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control
      EDL), was found. The results show that muscle deconditioning induces a
      biochemical and functional slow to fast phenotype transition in myofibrillar and
      cytosolic compartments of postural muscle, but not in the mitochondrial
      compartment, suggesting that these compartments are differently regulated under
      conditions of decreased activity.

PMID- 9925375
TI  - Selective induction of Na,K-ATPase alpha3 subunit mRNA abundance in cardiac
      myocytes by retinoic acid.
AB  - Retinoic acid (RA) is a high affinity ligand for a nuclear receptor which
      regulates transcription in target cells. Specific effects of RA on cardiac
      development and myocardial cell hypertrophy have been demonstrated; however,
      little information exists concerning RA-mediated regulation of cardiac genes.
      This study was initiated to investigate whether RA regulates Na,K-ATPase subunit
      gene expression in primary cultures of neonatal rat cardiac myocytes. Northern
      blot analyses demonstrated that NA, K-ATPase alpha3 subunit mRNA content was
      stimulated three-fold by RA. The effect of RA on alpha3 subunit gene expression
      was selective as RA treatment had no effect on either Na,K-ATPase alpha1, alpha2
      or beta1 subunit mRNAs. A stimulatory effect of RA on Na,K-ATPase alpha3 gene
      transcription was not evident in either transient transfection or nuclear run-on
      studies, suggesting that augmentation of alpha3 mRNA content by RA was due to a
      post-transcriptional mechanism. Finally, RA diminished the magnitude of the
      thyroid hormone (T3)-mediated increase in Na,K-ATPase beta1 subunit mRNA, while
      RA had no effect on the stimulation of alpha3 mRNA content by T3.

PMID- 9925376
TI  - Increased expression of connective tissue growth factor in the infarct zone of
      experimentally induced myocardial infarction in rats.
AB  - Connective tissue growth factor (CTGF), a 36- to 38-kDa peptide, is selectively
      induced by transforming growth factor-beta and has been suggested to contribute
      to tissue repair. To test the hypothesis that CTGF is expressed in myocardial
      infarct tissue following acute myocardial infarction (AMI), we examined CTGF
      expression after AMI was experimentally induced in rats. Myocardial infarction
      was induced by left coronary artery ligation in male Sprague-Dawley rats.
      Northern blotting demonstrated that the CTGF mRNA expression on days 2, 7 and 14
      was increased by 6-, 23- and 8-fold, respectively, compared to that in the pre
      ligation hearts. In situ hybridization revealed CTGF mRNA signals on day 2 in
      myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells
      (presumably myofibroblasts and fibroblasts) located between surviving myocytes in
      the infarct peripheral zone. On day 7, the signals were observed in the inner
      lesion of the infarct around infarct granulation tissue. Western blotting
      demonstrated that the CTGF protein expression on days 2, 7 and 14 was increased
      compared to the pre-ligation hearts. Immunopositive staining for CTGF was
      observed in the inner lesion of the infarct tissue on day 7. In conclusion, the
      findings demonstrated the increased expression of CTGF in the infarct tissue.
      Myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells
      (presumably myofibroblasts and fibroblasts) were the cells responsible for CTGF
      production.

PMID- 9925377
TI  - Activation of alpha1-adrenergic receptor during Ca2+ pre-conditioning elicits
      strong protection against Ca2+ overload injury via protein kinase C signaling
      pathway.
AB  - The objective was to test the hypothesis that transient activation of the alpha1
      adrenergic receptor mimics the beneficial effects of Ca2+ preconditioning on the
      Ca2+ paradox (Ca2+ PD) injury in rat hearts, and that the protection is mediated
      by protein kinase C (PKC) signaling pathway. Langendorff-perfused rat hearts were
      subjected to the Ca2+ PD (10 min of Ca2+ depletion followed by 10 min of Ca2+
      repletion). The effects of alpha1-adrenergic receptor activation and other
      interventions on functional, biochemical and pathological changes were assessed.
      In hearts pretreated with 50 micromol/l phenylephrine, left ventricular end
      diastolic pressure and coronary flow were significantly preserved after Ca2+ PD;
      furthermore, peak loss of lactate dehydrogenase was significantly decreased while
      ATP was significantly preserved. A remarkable preservation of cell structure was
      observed in phenylephrine-treated hearts in contrast to non-treated Ca2+ PD
      hearts. However, pre-conditioning elicited by phenylephrine caused only a mild
      improvement in left ventricular developed pressure (LVDP) as opposed to its
      impressive recovery of left ventricular end-diastolic pressure (LVEDP), heart
      rate (HR), or coronary flow (CF). The salutary effects of phenylephrine on the
      Ca2+ PD injury were almost similar to those observed in hearts which underwent
      Ca2+ pre-conditioning (CPC) or were pretreated with 1-stearoyl-2-arachidonoyl
      glycerol (SAG), a potent PKC activator. In phenylephrine pretreated hearts, PKC
      isoform-alpha was localized in the sarcolemma and nucleus, while PKC-delta and
      PKC-epsilon were localized in the cell membrane, and intercalated disk
      respectively. Prazosin, a specific alpha1-adrenergic receptor antagonist
      completely abolished the beneficial effects of phenylephrine on the Ca2+ PD and
      blocked translocation of PKC isoforms. In addition, prazosin (1 micromol/l) also
      reversed salutary effects of CPC. Moreover, the beta-adrenergic antagonist,
      propranolol, had no effect on the protection provided by phenylephrine against
      the Ca2+ PD injury. This study suggests that the activation of the alpha1
      adrenergic receptor confers protection against the lethal injury of the Ca2+ PD
      via PKC-mediated signaling pathways. The protection is shared by stimuli common
      with calcium pre-conditioning.

PMID- 9925378
TI  - Cytoplasmic sodium, calcium and free energy change of the Na+/Ca2+-exchanger in
      rat ventricular myocytes.
AB  - The relationship between changing driving force of the Na+/Ca2+-exchanger
      (deltaG(exch)) and associated cytosolic calcium fluxes was studied in rat
      ventricular myocytes. DeltaG(exch) was abruptly reversed by the reduction of
      extracellular sodium ([Na+]o) with or without sustained depolarization by the
      elevation of potassium ([K+]o). Cytosolic sodium ([Na+]i) and calcium ([Ca2+]i)
      were measured with SBFI and indo-1 respectively and the time course of recovery
      of deltaG(exch) was calculated. Following abrupt reversal of deltaG(exch) from
      +4.1 to -9.2 kJ/mol [Na+]i exponentially decreased from 9.6-2.5 mmol/l (t(1/2)
      about 30 s) and [Ca2+]i transiently increased to a peak value after about 30 s.
      Negative values of deltaG(exch) were associated with an increase and positive
      values with a decrease of [Ca2+]i. Equilibrium (deltaG(exch) = 0) was reached
      after about 30 s coinciding with the time to peak [Ca2+]i. After 180 s
      deltaG(exch) reached a new steady state at +3.5 kJ/mol. Inhibition of SR with
      ryanodine or thapsigargin reduced the amplitude of the [Ca2+]i transient and
      shifted its peak to 80 s, but did not affect the time course of [Na+]i changes.
      In the presence of ryanodine or thapsigargin the time required for deltaG(exch)
      to recover to equilibrium was also shifted to 80 s. When we changed the
      deltaG(exch) to the same extent by the reduction of [Na+]o in combination with a
      sustained depolarization, [Na+]i decreased less and the amplitude of [Ca2+]i
      transient was much enhanced. This increase of [Ca2+]i was completely abolished by
      verapamil. DeltaG(exch) only recovered to a little above equilibrium (+1 kJ/mol).
      Inhibition of the Na+/K+-ATPase with ouabain entirely prevented the decrease of
      [Na+]i and caused a much larger increase of [Ca2+]i, which remained elevated;
      deltaG(exch) recovered to equilibrium and never returned to positive values. The
      rate of change of total cytosolic calcium was related to deltaG(exch), despite
      the fact that the calcium flux associated with the exchanger itself contributed
      only about 10%; SR related flux contributed by about 90% to the rate of change of
      total cytosolic calcium. In summary, reduction of [Na+]o causes reversal of the
      Na+/Ca2+-exchanger and its driving force deltaG(exch), a transient increase of
      [Ca2+]i and a decrease of [Na+]i. The influx of calcium associated with reversed
      deltaG(exch) triggers the release of calcium from SR. Both the decrease of [Na+]i
      and the increase of [Ca2+]i contribute to the recovery of deltaG(exch) to
      equilibrium. The time at which deltaG(exch) reaches equilibrium always coincides
      with the time to peak of [Ca2+]i transient. Activation of the Na+/K+-ATPase is
      required to reduce [Na+]i and recover deltaG(exch) to positive values in order to
      reduce [Ca2+]i. We conclude that deltaG(exch) is a major regulator of cytosolic
      calcium by interaction with SR.

PMID- 9925379
TI  - Apoptosis of skeletal muscle myofibers and interstitial cells in experimental
      heart failure.
AB  - Congestive heart failure (CHF) is characterized by a limb skeletal muscle
      myopathy with shift from the slow aerobic, fatigue resistant fibers, to the fast,
      anaerobic ones, and muscle bulk loss. Apoptosis (A) has been recently
      demonstrated to play a role in several cardiovascular diseases. AIM OF THE STUDY:
      we have investigated the role of A in the skeletal muscle of the hindlimbs in an
      experimental model of CHF. ANIMALS AND METHODS: CHF was induced in 7 males 80-100
      g Sprague-Dawley rats with 30 mg/kg monocrotaline. Five age and diet matched
      controls were also studied. The time course of A was also studied in additional
      animals at day 0, 17, 24 and 30 days. RESULTS: At day 27 the electrophoretic
      analysis of myosin heavy chains (MHCs) demonstrated in the CHF rats the
      occurrence of a myopathy, with disappearance of slow MHC1 in the Tibialis
      Anterior (TA), and a significant shift from the slow to the fast isoforms in the
      soleus and EDL. With in situ DNA nick-end labelling (TUNEL) we found in the TA of
      CHF animals a significantly higher number of TUNEL positive nuclei (0.43 +/- 0.24
      v 0.08 +/- 0.02, P<0.02 and TUNEL positive myonuclei (0.031 +/- 0.012 v 0.0025 +/
      0.005, P<0.02). The time course of A showed a progressive rise in interstitial
      and myocyte A, accompanied by a drop in fibers cross-sectional area and muscle
      weight/body weight, that came out to be significant at 30 days. Western blot
      showed a lower expression of Bcl-2 at 27 days and a further drop at 30 days in
      the CHF rats. Double staining for TUNEL and antibody against anti-MHC2a and anti
      MHC2b + 2x showed that A occurs non-selectively in all the myofiber types.
      BetaANP and Right Ventricle Mass/Volume (RVM/V) correlated significantly with
      total apoptotic nuclei. CONCLUSIONS: In CHF myofibers A can lead to muscle
      atrophy. Endothelial cells A may produce an imbalance in myofibres nutrition with
      relative ischemia that triggers the preferential synthesis of fast anaerobic
      myosin as an adaptive mechanism or alternatively induce myofibres death.

PMID- 9925380
TI  - Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in
      canine ischemic myocardium.
AB  - Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart,
      ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood
      flow. On the other hand, since ACE inhibitors also inhibit kininase II which
      results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac
      nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was
      undertaken to test whether ACE inhibitors increase the cardiac NO levels and
      coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left
      anterior descending coronary artery was perfused through an extracorporeal bypass
      tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3
      microg/kg/min was infused into the bypass tube for 10 min after reduction of
      coronary blood flow due to partial occlusion of the bypass tube, coronary blood
      flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite
      no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of
      either imidaprilat or cilazaprilat, bradykinin and the end-products of NO
      (nitrate + nitrite) concentrations of coronary venous blood were markedly
      increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin
      receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO
      synthase). We also observed increases in cardiac bradykinin and NO levels due to
      either imidaprilat or cilazaprilat in the low constant coronary blood flow
      condition. It is concluded that ACE inhibitors can increase cardiac NO levels via
      the accumulation of bradykinin in the ischemic myocardium.

PMID- 9925381
TI  - Nitric oxide synthase in experimental autoimmune myocarditis dysfunction.
AB  - This study reports the expression of inducible nitric oxide synthase (NOS) in
      heart from autoimmune myocarditis mice associated with an alteration in their
      contractile behavior. By mean of the production of [U-14C]citrulline from [U
      14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in
      autoimmune atria that was normally absent. The iNOS activity decreased with
      administration of dexamethasone and in mice treated with monoclonal anti
      interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase
      C activity (staurosporine) but not calcium/calmodulin (trifluoperazine)
      attenuated the iNOS activity. Moreover, autoimmune atria presented contractile
      alterations (lower values of dF/dt than control). The in vivo treatment with
      inhibitors of NOS activity or anti-IFN-gamma mAb or dexamethasone improved the
      contractile activity of autoimmune atria with no change in the contractility of
      normal atria. The results suggest that the infiltrative cells in myocarditis
      heart have a potential role in cardiac dysfunction by production of IFN-gamma and
      subsequent expression of iNOS, that in turn alter the contractile behavior of the
      heart. The data indicate that cytokines induced activation of L-arginine nitric
      oxide pathway in myocarditis atria leading to contractile dysfunction.

PMID- 9925382
TI  - mRNA expression of glycolytic enzymes and glucose transporter proteins in
      ischemic myocardium with and without reperfusion.
AB  - It is known that ischemia commonly increases exogenous glucose utilization by
      accelerating glucose uptake and flux rates through the Embden-Meyerhof pathway.
      Constitutive enzymes regulate the rate of glycolysis and in turn are regulated by
      product inhibition and allosteric controls. The purpose of this report was to
      test whether mRNA abundance for select glycolytic enzymes, and glucose transport
      proteins, is also modified. Six intact working pig hearts with coronary flow
      controlled by extracorporeal perfusion were compared at the following conditions:
      (1) aerobic control perfusion; (2) ischemia affected by a 60% decrease in left
      anterior descending (LAD) coronary perfusion: (3) ischemia again affected by a
      60% decrease in LAD flow followed by a 40-min interval of aerobic reflow; (4) an
      intermittent ischemia and reflow protocol including four cycles of similar LAD
      flow reductions (5 min per cycle) interspersed with 15-20 min of aerobic
      reperfusion; (5) a 4-day model designed to produce myocardial chronic
      hibernation: and (6) mild ischemia induced by a 40% decrease in LAD flow for 85
      min to produce certain adaptations compatible with short-term hibernation. In
      each heart, mRNA abundance was measured from LAD and circumflex (LCF) perfused
      myocardium for hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate
      dehydrogenase and the two glucose transporter isomers, GLUT 4 and GLUT 1. mRNA
      data from LAD myocardium in intervention hearts were normalized to those from LAD
      tissue in the control heart (LADc) and with LCF values in the same intervention
      hearts. Signal variance around unity in the LAD tissue, with respect to that of
      the LCF myocardium, in the control heart compared closely (44 and 41% in two
      separate runs, respectively). GLUT 1/GLUT 4 ratios in the LAD and LCF beds of
      this heart also agreed closely. LAD/LADc ratios were increased for hexokinase
      (1.69), phosphofructokinase (3.69), and glyceraldehyde-3-phosphate dehydrogenase
      (2.29) in the ischemia heart and for phosphofructokinase (3.90), glyceraldehyde-3
      phosphate dehydrogenase (2.20), GLUT 4 (1.55) and GLUT 1 (2.20) in the
      ischemia/reflow heart. There was no evidence of excess signal in the intermittent
      ischemia/reflow, chronic hibernation, or mild ischemia hearts. Altered signal
      from LCF myocardium was also suggested. These data indicate that mRNA abundance
      for select glycolytic enzymes and transporter proteins is increased in ischemic
      myocardium with or without reperfusion and offers a possible mechanism for
      increased protein activity in settings of diminished regional coronary flow.

PMID- 9925383
TI  - Fatty acid ethyl esters: potentially toxic products of myocardial ethanol
      metabolism.
AB  - The chronic consumption of alcohol has proven detrimental to heart tissue and can
      lead to alcohol-induced heart muscle disease, a condition which may result in
      arrhythmias, cardiomegaly, and congestive heart failure. A search for the
      molecular mechanism underlying observed alcohol-induced end-organ damage, such as
      that seen in heart, has lead to the discovery of a nonoxidative pathway for the
      metabolism of alcohol in several human tissues including heart, brain, pancreas,
      and liver. It has been revealed that nonesterified fatty acids are esterified
      with ethanol to produce fatty acid ethyl esters (FAEE), neutral molecules which
      can accumulate in mitochondria and impair cell function. The observation that
      FAEEs are synthesized at high rates in the heart, and other organs that lack
      oxidative ethanol metabolism, provides a plausible link between the observed
      tissue damage, the ingestion of alcohol, and the subsequent development of
      alcohol-induced heart muscle disease. The synthesis of FAEEs are catalyzed by
      FAEE synthase enzyme, four of which have been characterized and purified to
      homogeneity from the human myocardium. Further analysis of these FAEE synthase
      enzymes opens up a new possibility to characterize and map a gene for alcohol
      induced end-organ damage, such as that observed in heart and other organs. FAEEs
      have been found to be important metabolites of alcohol and are most commonly
      accumulated in those organs which are damaged by alcohol abuse, i.e. heart. It
      may now be important to establish a genetic link between alcohol abuse and
      alcohol-induced heart muscle disease in order to understand the mechanism of
      alcohol-induced cardiomyopathy.

PMID- 9925384
TI  - An activator protein-1 (AP-1) response element on pro alpha1(l) collagen gene is
      necessary for thyroid hormone-induced inhibition of promoter activity in cardiac
      fibroblasts.
AB  - Thyroid hormone-induced ventricular hypertrophy is characterized by the absence
      of fibrosis. Previously, we demonstrated that thyroid hormone inhibits collagen
      type I gene expression in the myocardium and in cardiac fibroblasts. We also
      demonstrated that thyroid hormones act as inhibitor of pro alpha1(l) collagen
      promoter activity. In this study we determined the sequences on pro alpha1(l)
      collagen gene and transcription factors in cardiac fibroblasts involved in the
      inhibitory effect of 3,3',5-triiodothyronine (T3). Transient transfection of
      cells with chloramphenicol acetyl transferase (CAT)-linked deletion mutants of
      pro alpha1(l) collagen promoter demonstrated that the inhibitory effect of T3 is
      transmitted via proximal sequences(-225/+115). Gel shift analysis using [32P]
      labeled -225/+115 gene fragment and nuclear proteins of cardiac fibroblasts
      showed T3-induced DNA binding by two proteins. Analysis of non-overlapping
      restriction sub-fragments by gel shift along with supershift analysis with
      antibodies to types alpha and beta thyroid hormone receptors identified the lower
      molecular weight DNA-binding protein as beta receptor and confirmed that the T3
      induced protein-DNA binding sites are located at -15/+115. Selective base
      mutation (C in place of G at +93 and G in place of C at +97) in the activator
      protein-1 (AP-1) core binding motif(+92/+97) abolished the higher molecular
      weight T3-induced DNA-protein complex obtained with [32P]-labeled wild type
      sequences (-225/+115). Additional gel shift analyses using an oligonucleotide
      containing the AP-1 core binding motif, as an unlabeled competitor and as [32P]
      labeled probe, confirmed the T3-induced protein binding to an AP-1 site.
      Transient transfection with CAT-linked -225/+115 sequences in which the AP-1 site
      was mutated abolished the T3-induced inhibition of CAT activity. Together, these
      findings identify sequences necessary for T3-induced inhibition of collagen type
      I promoter to which thyroid hormone receptor type beta and protein(s) with
      affinity for AP-1 element bind. They also demonstrate that the AP-1 response
      element located on these sequences is necessary for T3-induced inhibition of pro
      alpha1(l) collagen promoter activity. These data identify molecular mechanisms
      involved in thyroid hormone-induced inhibition of collagen expression in the
      heart.

PMID- 9925385
TI  - Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal
      and hypertrophied rat myocardium.
AB  - The direct inotropic effect of angiotensin II on the myocardium is still
      controversial and little information exists as to its potential modification by
      heart disorders. Therefore, this study performed simultaneous measurements of
      isometric force and intracellular Ca2+ concentrations ([Ca2+]i) in left
      ventricular papillary muscles from sham-operated and aortic-banded rats at 10
      weeks post-surgery. Angiotensin II (10(-6) M) induced a reduction of peak
      systolic [Ca2+]i (0.56 +/- 0.03 to 0.48 +/- 0.04 microM; P<0.05) and a parallel
      but insignificant diminution of developed tension (10.5 +/- 1.3 to 9.6 +/- 0.8
      mN/mm2) in normal papillary muscles from sham-operated animals. Hypertrophied
      papillary muscles from aortic-banded rats demonstrated a significant decline in
      both peak systolic [Ca2+]i (0.51 +/- 0.02 to 0.44 +/- 0.01 microM; P<0.05) and
      developed tension (8.4 +/- 1.1 to 6.8 +/- 1.7 mN/mm2; P<0.05) after addition of
      angiotensin II. The time courses of the mechanical contraction and the
      intracellular Ca2+ signal were prolonged by angiotension II in both groups.
      Isoproterenol dose-dependently increased developed tension and peak systolic
      [Ca2+]i in papillary muscles from sham-operated rats. In contrast, the positive
      inotropic response to isoproterenol was markedly reduced in hypertrophied muscles
      despite a seemingly unimpaired increase in peak systolic [Ca2+]i. Pretreatment
      with angiotensin II (10(-6) M) resulted in a significant attenuation of the
      systolic [Ca2+]i response to isoproterenol stimulation in both normal and
      hypertrophied papillary muscles. Neither the bradykinin B2 antagonist icatibent
      (10(-6) M) nor the nitric oxide (NO) inhibitor L-NMMA (10(-6) M) abolished the
      depressant effects of angiotension II. Thus, ANG II induces a parallel decline of
      the mechanical performance and Ca2+ availability in rat myocardium. These effects
      are more distinct in hypertrophied than in normal muscle and become accentuated
      during beta-adrenergic stimulation. The underlying mechanism is not associated
      with the NO pathway but might involve a negative functional coupling between the
      angiotensin and beta-adrenergic-receptor complex.

PMID- 9925386
TI  - Metabolic differences between hearts of patients with aortic valve disease and
      hearts of patients with ischaemic disease.
AB  - The hypertrophic hearts of patients with aortic valve disease are likely to have
      metabolic demands different from hearts with ischaemic disease. In this study we
      measured the myocardial concentration of ATP, ADP, lactate and 16 different amino
      acids in left ventricular biopsies collected from patients with aortic valve
      disease and from patients with ischaemic heart disease. Compared to hearts with
      ischaemic disease, hypertrophic hearts had significantly higher concentrations of
      ATP, but lower concentrations of lactate, branched-chain amino acids and alanine.
      These differences have important implications for energy metabolism and protein
      turnover in the two pathologies.

PMID- 9925387
TI  - Abstracts of the XV Meeting of the Japanese Section of the International Society
      for Heart Research. "Potassium Channels in Cardiovascular Diseases and
      Cardioprotection". December 9-11, 1998, Tokyo, Japan.

PMID- 9925388
TI  - Voice recognition transcription: surely the future but is it ready?

PMID- 9925389
TI  - MR pancreatography: a useful tool for evaluating pancreatic disorders.
AB  - Magnetic resonance (MR) pancreatography is being used with increasing frequency
      as a noninvasive alternative to diagnostic endoscopic retrograde pancreatography
      in the evaluation of the pancreatic duct and various pathologic conditions of the
      pancreas. This recently developed technique allows improved spatial resolution
      and permits imaging of the entire pancreatico-biliary tract during a single
      breath hold. MR pancreatography can help identify the course and drainage pattern
      of the pancreatic duct and is useful in diagnosing congenital anomalies such as
      pancreas divisum and annular pancreas without the risk of inducing pancreatitis.
      In some instances, MR pancreatography may demonstrate duct disruption and
      associated fluid collections resulting from trauma. In recurrent acute
      pancreatitis, MR pancreatography is useful in suggesting the cause of the
      disease; in chronic pancreatitis, it is useful in depicting ductal anatomy,
      detecting strictures or intraductal calculi prior to surgery, and detecting
      complications such as pseudocysts and fistulas. In addition, MR pancreatography
      performed in conjunction with abdominal MR imaging is useful in identifying
      pancreatic malignancies as well as in establishing resectability and preventing
      unnecessary preoperative stent placement.

PMID- 9925390
TI  - MR cholangiography: technical advances and clinical applications.
AB  - Magnetic resonance (MR) cholangiography is a fast, accurate, noninvasive
      alternative to endoscopic retrograde cholangiography (ERC) in the evaluation of
      biliary tract disease. Technical improvements in imaging sequences (eg, half
      Fourier rapid acquisition with relaxation enhancement) and use of phased-array
      coils allow high-quality imaging comparable to that available with ERC. In
      choledocholithiasis, common bile duct stones as small as 2 mm can be detected
      with MR cholangiography and appear as low-signal-intensity foci within the high
      signal-intensity bile. MR cholangiography may help establish the diagnosis of
      malignant obstruction and is useful in the evaluation of patients in whom ERC was
      unsuccessful or incomplete. The role of MR cholangiography in the evaluation of
      intrahepatic duct disease continues to evolve. MR cholangiography plays a crucial
      role in evaluating postsurgical biliary tract alterations and can be used to
      demonstrate a variety of congenital anomalies of the biliary tract (eg, aberrant
      ducts, choledochal cysts, pancreas divisum). In addition, intentional or
      incidental imaging of the gallbladder with MR cholangiography can be used to
      identify calculi or help determine the presence and extent of neoplastic disease.

PMID- 9925391
TI  - Aortic dissection: diagnosis and follow-up with helical CT.
AB  - Acute aortic dissection is a cardiovascular emergency that requires prompt
      diagnosis and treatment. Helical computed tomography (CT) allows diagnosis of
      acute aortic dissection with a sensitivity and specificity of nearly 100%. With
      helical CT, a dissection involving the ascending aorta (type A in the Stanford
      classification) can be differentiated from one distal to the left subclavian
      artery (type B). Helical CT can also be used to identify atypical forms of aortic
      dissection such as intramural hematoma, penetrating atherosclerotic ulcer,
      ruptured type B dissection, and atypical configurations of the intimal flap.
      Helical CT is useful in follow-up of aortic dissection by allowing assessment of
      early and late changes after surgery or medical treatment. Such changes include
      postoperative complications of type A dissection, healing of intramural hematoma,
      progression of intramural hematoma, and aneurysms of the true or false lumen.
      Helical CT can also be used to monitor potentially life-threatening ischemic
      complications of abdominal branch vessels.

PMID- 9925392
TI  - Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign
      variants.
AB  - A rapidly emerging clinical application of positron emission tomography (PET) is
      the detection and staging of cancer with the glucose analogue tracer 2-[fluorine
      18]fluoro-2-deoxy-D-glucose (FDG). Proper interpretation of FDG PET images
      requires knowledge of the normal physiologic distribution of the tracer,
      frequently encountered physiologic variants, and benign pathologic causes of FDG
      uptake that can be confused with a malignant neoplasm. One hour after intravenous
      administration, high FDG activity is present in the brain, the myocardium, and-
      due to the excretory route--the urinary tract. Elsewhere, tracer activity is
      typically low, a fact that allows sensitive demonstration of tracer accumulation
      in many malignant neoplasms. Interpretive pitfalls commonly encountered on FDG
      PET images of the body obtained 1 hour after tracer administration can be
      mistaken for cancer. Such pitfalls include variable physiologic FDG uptake in the
      digestive tract, thyroid gland, skeletal muscle, myocardium, bone marrow, and
      genitourinary tract and benign pathologic FDG uptake in healing bone, lymph
      nodes, joints, sites of infection, and cases of regional response to infection
      and aseptic inflammatory response. In many instances, these physiologic variants
      and benign pathologic causes of FDG uptake can be specifically recognized and
      properly categorized; in other instances, such as the lymph node response to
      inflammation or infection, focal FDG uptake is nonspecific.

PMID- 9925393
TI  - Correlation of lesion appearance and histologic findings for the nodes of a
      breast MR imaging interpretation model.
AB  - An interpretation model for evaluating magnetic resonance (MR) images of the
      breast was constructed that allowed differentiation of benign from malignant
      palpable or mammographically visible abnormalities. Architectural features define
      each node of the model. Investigation was subsequently made of the histologic
      findings in individuals within each node and of the frequency with which each
      histologic finding manifested as a particular architectural feature to determine
      whether nodal location and specific histologic findings are mutually predictive.
      The strongest associations were found between fibrocystic change and smooth
      masses, fibroadenoma and lobulated masses with nonenhancing internal septations,
      invasive ductal carcinoma (with or without ductal carcinoma in situ [DCIS]) and
      enhancing irregular or spiculated masses, invasive tubular carcinoma or radial
      scar and spiculated masses, medullary or colloid carcinoma and enhancing
      lobulated masses, invasive lobular carcinoma and the absence of a focal mass,
      DCIS and ductal enhancement, and DCIS (with or without invasive ductal carcinoma)
      and regional enhancement. Nodal location and histologic findings proved to be
      mutually predictive within the model; that is, the nodal location of MR imaging
      features within the model can be used to predict histologic findings and vice
      versa.

PMID- 9925394
TI  - Lumbar facet joint arthrography with the posterior approach.
AB  - Lumbar facet joint (LFJ) arthrography with intraarticular injections of long
      acting steroids and local anesthetics is routinely used for therapeutic purposes
      in selected patients for relief of low back pain. The procedure may also be used
      for diagnostic reasons to establish the source of such pain. However, because
      direct access to the LFJ space is not always possible owing to degenerative
      changes such as osteophytes, another posterior approach has been proposed for LFJ
      arthrography. With the patient in the prone position, a spinal needle is inserted
      vertically into the inferior recess of an LFJ with fluoroscopic guidance and the
      patient under local anesthesia. To facilitate puncture, cushions are placed under
      the patient's abdomen to flatten normal lumbar lordosis, which enlarges the
      inferior recess of the LFJ. Use of cushions also results in a decrease in tissue
      thickness in the patient, thereby improving image quality and decreasing
      radiation exposure. LFJ arthrography can demonstrate the causative role of facet
      disease in abnormalities responsible for low back pain or sciatica and can be
      performed easily and rapidly with this direct posterior approach.

PMID- 9925395
TI  - The ribs: anatomic and radiologic considerations.
AB  - The ribs are essential structures of the osseous thorax and provide information
      that aids in the interpretation of radiologic images. Techniques for making
      precise identification of the ribs are useful in detection of rib lesions and
      localization of lung lesions. The big rib sign and the vertical displacement sign
      can be used to differentiate the right and left ribs on lateral chest
      radiographs. The clavicle, the xiphoid process, and the sternal angle may be used
      as anatomic landmarks for rib counting on computed tomographic scans. For rib
      counting on lateral chest radiographs, the sternal angle or the 12th rib may be
      used. Anatomic rib variants include developmental deformities, cervical rib, and
      short rib and may mimic true rib diseases. Detection of thoracic deformities such
      as funnel chest (pectus excavatum) and barrel-shaped thorax requires an awareness
      of the strong correlation between the transverse appearance of the thorax and
      costal shape. Shadows around the rib cage (eg, rib companion shadows, sharp lines
      along the lower margin of the ribs, rib overlying shadows) may mimic pleural and
      extrapleural disease on frontal chest radiographs. It is imperative that the
      radiologist be familiar with normal rib anatomy, normal rib variants, and the
      radiologic appearance of the ribs to prevent misdiagnosis.

PMID- 9925396
TI  - Congenital cystic masses of the neck: radiologic-pathologic correlation.
AB  - Cervical congenital cystic masses constitute an uncommon group of lesions usually
      diagnosed in infancy and childhood. The most common congenital neck mass is the
      thyroglossal duct cyst. The diagnosis is easily established from the presence of
      a cystic lesion in the anterior midline portion of the neck. The vast majority of
      branchial cleft cysts arise from the second branchial cleft. They can occur
      anywhere from the oropharyngeal tonsillar fossa to the supraclavicular region of
      the neck. Cystic hygroma is the most common form of lymphangioma. In the neck,
      cystic hygromas are most commonly found in the posterior cervical space. They
      typically extend into adjacent structures without respecting the fascial planes.
      Dermoid and epidermoid cysts result from sequestration of ectodermal tissue. The
      floor of the mouth is the most common location in the neck. Cervical thymic cysts
      are very uncommon lesions and are found anywhere from the angle of the mandible
      down to the sternum. Laryngoceles are classified into internal, external, and
      mixed types and have a frequent association with laryngeal carcinoma.

PMID- 9925397
TI  - Radiation interactions and internal dosimetry in nuclear medicine.
AB  - The decay of a radioactive nucleus leads to the emission of energy in the form of
      photons or charged particles. The form and energy of the radiation emitted will
      depend on the decaying nucleus. Some of the emitted energy will be absorbed by
      target organs; the ratio of the absorbed energy to the mass of the target is the
      radiation dose. Charged particles traveling in a medium slow down because of
      interactions between the electric charge of the particle and that of the orbital
      electrons and nuclei of the medium. These interactions transfer energy from the
      charged particle to the orbital electrons and the nuclei of the medium. A photon
      may be transmitted through a medium or may be attenuated by the medium. Of the
      four mechanisms by which photons interact with matter, two are important in the
      energy range of interest in nuclear medicine: the photoelectric effect and
      Compton scattering. The internal radiation dose from radionuclides used in
      nuclear medicine can be estimated with the Medical Internal Radiation Dose (MIRD)
      method. Important aspects of the MIRD method include the concepts of source and
      target organs, energy emitted per decay, absorbed fraction, S value, cumulated
      activity, and effective dose equivalent.

PMID- 9925398
TI  - A radiology department intranet: development and applications.
AB  - An intranet is a "private Internet" that uses the protocols of the World Wide Web
      to share information resources within a company or with the company's business
      partners and clients. The hardware requirements for an intranet begin with a
      dedicated Web server permanently connected to the departmental network. The heart
      of a Web server is the hypertext transfer protocol (HTTP) service, which receives
      a page request from a client's browser and transmits the page back to the client.
      Although knowledge of hypertext markup language (HTML) is not essential for
      authoring a Web page, a working familiarity with HTML is useful, as is knowledge
      of programming and database management. Security can be ensured by using scripts
      to write information in hidden fields or by means of "cookies." Interfacing
      databases and database management systems with the Web server and conforming the
      user interface to HTML syntax can be achieved by means of the common gateway
      interface (CGI), Active Server Pages (ASP), or other methods. An intranet in a
      radiology department could include the following types of content: on-call
      schedules, work schedules and a calendar, a personnel directory, resident
      resources, memorandums and discussion groups, software for a radiology
      information system, and databases.

PMID- 9925399
TI  - Prostatic carcinoma.

PMID- 9925401
TI  - Adrenal adenoma and hematoma mimicking a collision tumor at MR imaging.

PMID- 9925402
TI  - Pediatric case of the day. Ewing sarcoma of the rib with intraspinal extension.

PMID- 9925403
TI  - Breast imaging case of the day. Florid sclerosing adenosis.

PMID- 9925404
TI  - Gastrointestinal case of the day. Primary leiomyosarcoma of the IVC with Budd
      Chiari syndrome.

PMID- 9925405
TI  - General case of the day. Desmoplastic small round cell tumor of the abdomen with
      scrotal metastases.

PMID- 9925407
TI  - US case of the day. Complete brain duplication with fusion at the posterior fossa
      (diprosopus tetraophthalmos)

PMID- 9925406
TI  - Neuroradiology case of the day. Vertebral artery dissection and stroke.

PMID- 9925408
TI  - Meeting report. Neural Developments.

PMID- 9925409
TI  - 4th Annual meeting of the British HIV Association (BHIVA). Oxford, 27-29 March
      1998. Abstracts.

PMID- 9925410
TI  - Sedimentation of generalized systems of interacting particles. III. Concentration
      dependent sedimentation and extension to other transport methods.

PMID- 9925411
TI  - Compression therapy: a new demonstration of its effectiveness.

PMID- 9925412
TI  - Proceedings of the 12th International Conference on Lymphoid Tissues and Germinal
      Centers in Immune Reactions: Part 2.

PMID- 9925413
TI  - Thyrotropin-Releasing Hormone and Related Peptides on the Dawning of a New
      Millennium. Symposium proceedings. Kos, Greece, June 5-7, 1998.

PMID- 9925414
TI  - Proceedings of the 3rd International Conference on Advances in Pulmonary
      Rehabilitation and Management of Chronic Respiratory Failure. Florence, Italy,
      March 11-14, 1998. Part 2 of 2.

PMID- 9925415
TI  - Challenging tradition in the treatment of patellofemoral disorders.

PMID- 9925416
TI  - Research priorities in respiratory nursing.

PMID- 9925417
TI  - The enhanced Canadian dentists' investment program: serving you better.

PMID- 9925418
TI  - American Cancer Society Workshop on Breast Cancer Treatment-Related Lymphedema.
      New York, New York, USA. February 20-22, 1997.

PMID- 9925419
TI  - On the problem of a regulatory role of active oxygen species in cells.

PMID- 9925420
TI  - Project meeting report: International Workshop on Inuit Autopsy & Related
      Studies. October 2-3, 1997, Quebec, Canada.

PMID- 9925421
TI  - [Articles published in 1998].

PMID- 9925422
TI  - Primary breast lymphoma.
AB  - Breast involvement by non-Hodgkin lymphoma is uncommon. Differences between
      primary and secondary breast lymphoma have been well-defined. However,
      histopathological features, therapeutic approach and outcome are still debated.
      We report the clinical and pathological features of 5 cases of malignant lymphoma
      primarily involving the breast. The literature is extensively reviewed paying
      particular attention to pathological features, therapeutic approach and survival
      analysis. All patients were women; the median age was 63.2 yr. The clinical
      course was indistinguishable from that of breast carcinoma. High-grade lymphoma
      was found in 4 cases; T cell lineage antigens were expressed in one case. All
      patients were in stage I or II. Treatment consisted of chemotherapy and/or
      radiotherapy. The follow-up period ranged from 20 to 54 months (mean, 33.2). All
      patients are still in complete clinical remission. Analysis of the literature
      showed that about 80% of cases are high grade lymphoma. In this group, stage I at
      presentation statistically gives the best survival rate; surgery does not appear
      to have a role in high-grade lymphoma treatment.

PMID- 9925424
TI  - Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse
      transcriptase activity.
AB  - Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory
      system of bivalves, was first reported in oysters in 1969. Since that time, the
      disease has been determined to be transmissible through water-borne exposure, but
      the etiological agent has not been unequivocally identified. In order to
      determine if a viral agent, possibly a retrovirus, could be the causative agent
      of DN, transmission experiments were performed, using both a cell-free filtrate
      and a sucrose gradient-purified preparation of a cell-free filtrate of DN
      positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was
      used to determine if reverse transcriptase was present in tissues or hemolymph
      from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy
      clams by injection with whole DN cells, but not with cell-free filtrates prepared
      from either tissues from DN positive clams, or DN cells. The cell-free
      preparations from DN-positive tissues and hemolymph having high levels of DN
      cells in circulation exhibited positive reactions in the PCR-enhanced reverse
      transcriptase assay. Cell-free preparations of of hemolymph from clams having low
      levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams,
      and normal soft shell clam tissues did not produce a positive reaction in the PCR
      enhanced reverse transcriptase assay.

PMID- 9925423
TI  - Gastric cancer: epidemiologic and biological aspects.
AB  - Although temporal trends and regional-racial variations in gastric cancer
      incidence have led to the formulation of different hypotheses, no definite
      association has been seen between this disease and any behavioural or genetic
      determinant. In fact, several aetiological factors have been associated with risk
      of gastric cancer, but not without controversy. Various studies have suggested
      that genetic factors might be of importance in the pathogenesis of gastric
      tumours. In fact, stomach carcinoma occurs more frequently among close relatives
      of affected individuals than in the general population and some of the most
      common pre-cancerous lesions seem to be genetically determined. In the light of
      this circumstantial evidence, we decided to investigate the role of various
      genetic alterations in gastric cancer in order to study their relationship with
      aetiopathogenesis and disease progression and their value as indicators of risk
      and prognosis. Our main areas of interest were: i. c-Ha-ras locus polymorphism;
      ii, truncated c-myc gene variant; iii. loss of heterozygosity, iv. p53 gene
      mutations; v. oncogene amplification; vi. oncogene amplification proliferative
      activity and their relation to prognosis in gastric cancer.

PMID- 9925425
TI  - Goussia carpelli (Protozoa: Coccidia) infection in stressed and immunosuppressed
      common carp Cyprinus carpio.
AB  - Goussia carpelli causes enteritic coccidiosis in juvenile carp. In nature it
      affects carp fry (1 to 2 mo old) and fish (3 to 4 mo old) which are subjected to
      environmental stress. Carp treated with corticosteroids or subjected to
      temperature stress in the laboratory produced higher numbers of oocysts during
      the primary infection. Resistance to reinfection via the fecal contamination
      route, however, was not reduced by the application of hydrocortisone,
      dexamethasone, or X-ray irradiation given both prior to and concurrently with
      reinfection. The administration of hydrocortisole or irradiation did not induce a
      relapse of a previous infection. Carp which had been immunosuppressed by
      hydrocortisole injection during a primary infection were also refractory to a
      secondary infection via fecal contamination. The results of these experiments
      suggest that the mechanisms which are responsible for the resistance of carp to
      secondary infections with Goussia carpelli were not affected by hydrocortisole,
      dexamethasone or X-ray treatment.

PMID- 9925426
TI  - Cochliopodium minus, a scale-bearing amoeba isolated from organs of perch Perca
      fluviatilis.
AB  - A scale-bearing amoeba isolated from gills and other organs of perch Perca
      fluviatilis Linnaeus, 1758 was identified as Cochliopodium minus Page, 1976. This
      assignment was suggested by light microscopy and confirmed by ultrastructural
      study of both the strain isolated from perch and the environmental strain of C.
      minus (CCAP 1537/1A) serving as a control. This has been the first electron
      microscopic definition of C. minus and, in addition, the first identification of
      an amoeba with a theca-like cover found to infect fish. The ability of the fish
      strain of C. minus to colonize gills and also internal body organs was proved
      experimentally.

PMID- 9925427
TI  - Amphibians and larvae of aquatic insects as new paratenic hosts of Anguillicola
      crassus (Nematoda: Dracunculoidea), a swimbladder parasite of eels.
AB  - Amphibians (tadpoles of the frog Bombina bombina [L.] and the newt Triturus
      vulgaris [L.]) and aquatic insects (larvae of the alderfly Sialis lutaria [L.]
      [Megaloptera], dragonflies Sympetrum sanguineum [Miller] and Coenagrion puella
      [L.] [Odonata], and the caddisfly Oligotrichia striati [L.] [Trichoptera]) were
      found to serve as paratenic hosts for the third-stage larvae (L3) of the nematode
      Anguillicola crassus Kuwahara, Niimi et Itagaki, 1974, a pathogenic swimbladder
      parasite of the eel Anguilla anguilla (L.) in Europe and elsewhere. This is the
      first evidence that, in addition to prey fishes and some aquatic snails,
      amphibians and aquatic insects can serve as paratenic hosts for this nematode
      parasite. A. crassus third-stage larvae were found, largely unencapsulated
      (encapsulated only in S. lutaria), mostly in the body cavity, on the gut surface
      and, less often, in the liver and in the subcutaneous tissue of legs in
      amphibians, and in the body cavity and on the gut surface in insect larvae; they
      could survive for at least 49 d in T. vulgaris and 69 d in S. lutaria. The
      capability of these larvae from S. lutaria (69 d post-infection) to infect the
      definitive host (eel) was confirmed by experimental infection of an eel.

PMID- 9925428
TI  - Development of a nested polymerase chain reaction for amplification of a sequence
      of the p57 gene of Renibacterium salmoninarum that provides a highly sensitive
      method for detection of the bacterium in salmonid kidney.
AB  - Nucleic acid-based assays have shown promise for diagnosing Renibacterium
      salmoninarum in tissues and body fluids of salmonids. Development of a nested
      polymerase chain reaction (PCR) method to detect a 320 bp DNA segment of the gene
      encoding the p57 protein of R. salmoninarum is described. Whereas a conventional
      PCR for a 383 bp segment of the p57 gene reliably detected 1000 R. salmoninarum
      cells per reaction in kidney tissue, the nested PCR detected as few as 10 R.
      salmoninarum per reaction in kidney tissue. Two DNA extraction methods for the
      nested PCR were compared and the correlation between replicate samples was
      generally higher in samples extracted by the QIAamp system compared with those
      extracted by the phenol/chloroform method. The specificity of the nested PCR was
      confirmed by testing DNA extracts of common bacterial fish pathogens and a panel
      of bacterial species reported to cause false-positive reactions in the enzyme
      linked immunosorbent assay (ELISA) and the fluorescent antibody test (FAT) for R.
      salmoninarum. Kidney samples from 74 naturally infected chinook salmon were
      examined by the nested PCR, the ELISA, and the FAT, and the detected prevalences
      of R. salmoninarum were 61, 47, and 43%, respectively.

PMID- 9925429
TI  - In vitro studies of teicoplanin binding to rat tissues and erythrocytes.
AB  - Teicoplanin is a large polar antibiotic with a large distribution volume (Vss =
      1.2-2.8 l/kg) despite extensive binding to plasma albumin. To understand this
      observation, binding of 3H-teicoplanin to 10% rat tissue homogenates was
      determined in vitro by ultracentrifugation in the presence of teicoplanin (1-30
      microg/ml). Binding and efflux from erythrocytes were also studied. The in vitro
      total-to-unbound tissue concentration ratio (Kpu) differed widely but for each
      tissue was concentration independent. Upon correction for the plasma unbound
      fraction, there was discrepancy between the in vitro and in vivo tissue-to-plasma
      concentration ratios (KP), the latter calculated from previously published tissue
      and plasma concentration-time data using the area method. Moreover, calculation
      of Vss from in vitro Kp (8.10 l/kg) overestimated the in vivo value. These
      results suggest that in vivo teicoplanin binds to cell membranes and enters some
      but not all cells, such as erythrocytes.

PMID- 9925430
TI  - A bed-net safari.

PMID- 9925431
TI  - Death due to diphtheria.

PMID- 9925432
TI  - What type of travelers would benefit from combined vaccination against hepatitis
      A and B?

PMID- 9925433
TI  - Motion sickness--questions and answers.

PMID- 9925434
TI  - Change, relationships, and accountability: marks of a vibrant society.

PMID- 9925437
TI  - Treatment of hepatic metastases from colorectal carcinoma.

PMID- 9925438
TI  - Perspectives in amino acid and protein geochemistry. Proceedings of a conference.
      Washington DC, USA. April 5-7, 1998. Abstracts.

PMID- 9925436
TI  - Role of the ileocecal junction in the motor response to intestinal resection.
AB  - Extensive resections of the distal small intestine are associated with motor
      disruption in the proximal remnant. Luminal contents such as bacteria and short
      chain fatty acids may play a role. We evaluated the effect of bypass of the
      ileocecal junction (ICJ) on the motor response to a 50% distal resection. Thirty
      five dogs were divided into three groups: transection control (TC, n = 11); 50%
      distal resection with intact ICJ (DR, n = 12), and 50% distal resection with
      jejunocolostomy to bypass the ICJ (DRBP, n = 12). Motor activity, intestinal
      transit, nutrition, absorption, and motor active hormones were studied over a 3
      month period. Caloric intake was reduced and nutritional status similarly
      impaired in both resected groups. Steatorrhea, however, was significantly greater
      after DRBP. Intestinal structural adaptation was similar in both resected groups
      at 12 weeks. Animals in the bypass group demonstrated elevated intraluminal short
      chain fatty acid and anaerobic bacterial counts. Migrating motor complex
      frequency was similar in the three groups; distal starts, however, were more
      frequent in both resected groups. Clustered contractile activity was prominent in
      the remnant after both DR and DRBP (50% and 32% recording time occupied by
      clusters, respectively [not significant]). Basal levels of peptide YY were
      increased following resection and this increase was unaffected by ICJ bypass.
      Postprandial neurotensin concentrations were transiently increased after distal
      bowel resection. In contrast, the postprandial neurotensin response was abolished
      following resection with bypass of the ICJ. Basal motilin levels were reduced
      following resection alone but not after resection with ICJ bypass. The motor
      response to resection does not appear to be related to alterations in circulating
      levels of hormones localized to the distal ileum; neither does it seem to be
      influenced by luminal bacteria and short-chain fatty acids or retention of a
      sphincteric mechanism at the ICJ. These findings also raise questions about the
      role of short-chain fatty acids and bacteria in the generation of the various
      distinctive motor patterns of the distal ileum. Resection of the distal ileum
      through loss of the receptor site for either retarding reflexes or bile salt
      absorption may be of greater importance in determining the motor response to
      resection.

PMID- 9925435
TI  - The pathogenesis of cholesterol gallstones a review.

PMID- 9925439
TI  - Synthesis and biological evaluation of 2,2-disubstituted 2-aminoethanols:
      analogues of FTY720.
AB  - Desymmerization of symmetric FTY720 by substitution of different alkyl groups for
      one of the prochiral hydroxymethyl groups was performed. The size of the alkyl
      groups and the absolute configuration at quaternary carbon were important on
      immunosuppressive activity.

PMID- 9925440
TI  - Potent 3-spiropiperidine growth hormone secretagogues.
AB  - Systematic SAR studies of the different regioisomers and homologues of the
      spiro(indane-1,4-piperidine) moiety in the growth hormone secretagogue L-162,752
      are presented. Among them, spiro(3H-1-benzopyran-2,3-piperidine) was found to
      afford secretagogues with low nanomolar in vitro activity.

PMID- 9925441
TI  - Design and synthesis of a water-soluble taxol analogue: taxol-sialyl conjugate.
AB  - Glycosidation, using the methylthio derivative of N-acetylneuraminic acid 3, of
      linker alcohol 4 in DME with "long-range participation" produced the alpha
      glycosyl linkage with high stereoselectivity. The alpha-linked sialic acid 2 was
      introduced in taxol without protection of the alcohol functionality in sialic
      acid.

PMID- 9925443
TI  - Resources for women with epilepsy and health care providers.

PMID- 9925442
TI  - Proceedings of the John Coghlan Festschrift Symposium. Future Perspectives in
      Molecular Endocrinology. Melbourne, Australia, 30-31 October 1997.

PMID- 9925444
TI  - Retraction. Interferon-gamma is essential for the development of cerebral
      malaria.

PMID- 9925445
TI  - [French Pancreas Club. Saint-Malo, 15-17 October 1998. Abstracts].

PMID- 9925446
TI  - On the threshold of translating basic enteric neuroscience advances.

PMID- 9925447
TI  - Image of the month. Pneumatosis intestinalis.

PMID- 9925448
TI  - Do trypsin 2-alpha-1-antitrypsin complexes occur naturally in the circulation?

PMID- 9925449
TI  - Implant occlusion: revelations from the past 5 years.

PMID- 9925451
TI  - Introduction. Early identification and assessment of emerging health technology.

PMID- 9925450
TI  - The cytotoxic enterotoxin of Aeromonas hydrophila is aerolysin.

PMID- 9925453
TI  - 1st International Symposium. Rectal Cancer: Recent Advances in Diagnosis and
      Treatment. Germany, October 1-3, 1998. Abstracts.

PMID- 9925452
TI  - Care of Depression in Older Patients. Proceedings of a symposium. Copenhagen,
      Denmark, 7-8 November 1998.

PMID- 9925454
TI  - Proceedings of the Waltham International Symposium on Pet Nutrition and Health in
      the 21st Century. Orlando, Florida, USA. May 25-29, 1997.

PMID- 9925455
TI  - Impact of European policy on drug development.

PMID- 9925456
TI  - Prospective blinded study of the relationship between plasma homocysteine and
      progression of symptomatic peripheral arterial disease.
AB  - PURPOSE: An elevated plasma homocysteine level is an established risk factor for
      atherosclerotic coronary heart disease (CHD), cerebrovascular disease (CVD), and
      lower extremity occlusive disease (LED). An elevated plasma homocysteine level
      can be reduced by therapy with folate and vitamins B6 and B12. An accurate
      evaluation of the role of vitamin therapy requires knowledge of the influence of
      plasma homocysteine levels on the progression of CHD, CVD, and LED. METHODS: The
      Homocysteine and Progression of Atherosclerosis Study is a blinded prospective
      study of the influence of homocysteine and of other atherosclerotic risk factors
      on the progression of disease in patients with symptomatic CVD, LED, or both.
      This study is set in a university hospital vascular surgery clinic and the
      General Clinical Research Center. Consecutive patients with stable symptomatic
      CVD or LED underwent baseline clinical, laboratory, and vascular laboratory
      testing for homocysteine and other risk factors and were examined every 6 months.
      The primary endpoints were ankle brachial pressure index, duplex scan-determined
      carotid stenosis, and death. The secondary endpoints were the clinical
      progressions of CHD, LED, and CVD. The hypothesis that was tested was whether the
      progression of symptomatic CVD or LED was more frequent or more rapid in patients
      with elevated plasma homocysteine levels. plasma homocysteine levels. RESULTS:
      After a mean follow-up period of 37 months (range, 1 to 78 months) for deaths
      from all causes (>14 micromol/L; elevated, 18.6%; normal, 9.4%; P = .022), deaths
      from cardiovascular disease (elevated, 12.5%; normal, 6.3%; P = .05) and the
      clinical progression of CHD (highest 20% of homocysteine levels, 80%; lowest 20%
      of homocysteine levels, 39%; P = .007) were significantly more frequent or more
      rapid by life-table analysis when the homocysteine levels were elevated.
      Multivariate Cox proportional hazards regression model showed a significant
      independent and increasing relationship between the plasma homocysteine levels
      and the time to death (relative risk for highest one third of homocysteine
      values, 1.6; 95% confidence interval [CI], 1.04 to 2.56; P = 029; and relative
      risk for highest one fifth of homocysteine values, 3.13; 95% CI, 1.69 to 6.64; P
      = .0001). After an adjustment for age, smoking, hypertension, diabetes,
      cholesterol, and the vascular laboratory progression of CVD or LED, each 1.0
      micromol/L increase in the plasma homocysteine levels resulted in a 3.6% increase
      (95% CI, 0.0% to 6.6%; P = .06) in the risk of death (all causes) at 3 years and
      a 5.6% increase (95% CI, 2.2% to 8.5%; P = .003) in the risk of death from
      cardiovascular disease. CONCLUSION: We conclude that elevated plasma homocysteine
      levels are associated significantly with death, with death from cardiovascular
      disease, and with the progression of CHD in patients with symptomatic CVD or LED.
      These results strongly mandate clinical trials of homocysteine-lowering vitamin
      therapy in such patients.

PMID- 9925457
TI  - In memoriam. George Pearman Fulton, Jr. (1914-1998).

PMID- 9925458
TI  - [Antisense oligonucleotides arrest the synthesis of disease promoting proteins].

PMID- 9925459
TI  - AIDS--New Zealand.

PMID- 9925460
TI  - [Nordisk Medicine 1929-1998. Thanks and farewell!].

PMID- 9925461
TI  - [Scientific fraud and misconduct--need for comprehensive terminology].

PMID- 9925462
TI  - Stimarec report.

PMID- 9925463
TI  - Cancer resources in the United States.

PMID- 9925464
TI  - [Solutions in ambulatory child and adolescent psychiatry--study of clinical
      evaluation].
AB  - The effects of an systemic approach to outpatient child and adolescent psychiatry
      was hardly proved up to now. According to a study of clinical evaluation we
      analyzed a sample of more than 600 cases out of our work with about 1900
      children, adolescents and young adults and their families. This study includes a
      catamnestic exploration regarding to the two-years-outcome. As a result we found,
      that the systemic approach is of high clinical utility in outpatient therapy with
      young clients and their families. The indication of systemic therapy is
      discussed.

PMID- 9925466
TI  - [Regional group, the inbred strains, and the mutational strains of medaka].

PMID- 9925465
TI  - [Genetic resources of Drosophila melanogaster that support the progress of life
      sciences].

PMID- 9925467
TI  - Neuroscience institute breaks new ground.

PMID- 9925468
TI  - Which Jefferson was the father?

PMID- 9925469
TI  - Immortalized cells seem cancer-free so far.

PMID- 9925470
TI  - RNA study suggests cool cradle of life.

PMID- 9925471
TI  - American Society for Cell Biology. Bacteria pull cell skeletons out of the
      closet.

PMID- 9925472
TI  - American Society for Cell Biology. An all-purpose protein shock absorber.

PMID- 9925473
TI  - American Society for Cell Biology. Homing in on a sperm receptor.

PMID- 9925474
TI  - Ancient child burial uncovered in Portugal.

PMID- 9925475
TI  - Silver-tongued Neandertals?

PMID- 9925476
TI  - Fertility technique regulation.

PMID- 9925477
TI  - Beyond sloth--physical activity and weight gain.

PMID- 9925478
TI  - RNA, whither goest thou?

PMID- 9925480
TI  - T cell production slowed, not exhausted?

PMID- 9925479
TI  - Did early African hominids eat meat?

PMID- 9925481
TI  - How stimulant drugs may calm hyperactivity.

PMID- 9925482
TI  - Scientific leaders balk at broad data release.

PMID- 9925483
TI  - India prepares research, policy initiatives.

PMID- 9925484
TI  - Genetic engineers aim to soup up crop photosynthesis.

PMID- 9925485
TI  - Animal rights.

PMID- 9925486
TI  - Animal rights.

PMID- 9925487
TI  - Animal rights.

PMID- 9925488
TI  - Animal rights.

PMID- 9925489
TI  - Animal rights.

PMID- 9925490
TI  - Animal rights.

PMID- 9925491
TI  - Physician-scientists--endangered and essential.

PMID- 9925492
TI  - You are what you eat.

PMID- 9925494
TI  - Probing Europa's third dimension.

PMID- 9925493
TI  - HIV vaccines. Magic of the occult?

PMID- 9925495
TI  - What maintains memories?

PMID- 9925496
TI  - Cloning 3.0?

PMID- 9925497
TI  - Gene sequencing. Size matters.

PMID- 9925499
TI  - Nepal 1996: results from the family health survey.

PMID- 9925500
TI  - Proceedings of the 7th NRSP-7/USDA Workshop Drugs in Aquaculture: Current Status,
      Future Goals.

PMID- 9925498
TI  - Tanzania 1996: results from the demographic and health survey.

PMID- 9925501
TI  - [Taxotere in various solid tumors].

PMID- 9925502
TI  - Proceedings of the 4th Slide Workshop of the Society of Hematopathology.
      Extranodal hematopoietic/lymphoid disorders. Pittsburgh, Pennsylvania, USA.
      September 1997.

PMID- 9925503
TI  - Strategies for influencing outcomes in pre-ESRD and ESRD patients: a special
      conference. 1998. Proceedings.

PMID- 9925504
TI  - APIC position paper: prevention of device-mediated bloodborne infections to
      health care workers. Association for Professionals in Infection Control and
      Epidemiology, Inc.

PMID- 9925505
TI  - Absorbable self-reinforced poly-L-lactide wires, screws and rods in the fixation
      of fractures and arthrodeses and mini tacks in the fixation of ligament ruptures.

PMID- 9925506
TI  - Special issue dedicated to Dr. Willem Kolff on the 60th anniversary of his
      medical career.

PMID- 9925507
TI  - Genetic methods for assessing antimicrobial resistance.

PMID- 9925508
TI  - Comparative in vitro activities of meropenem, imipenem, temocillin, piperacillin,
      and ceftazidime in combination with tobramycin, rifampin, or ciprofloxacin
      against Burkholderia cepacia isolates from patients with cystic fibrosis.
AB  - We evaluated the activities of meropenem, imipenem, temocillin, piperacillin, and
      ceftazidime by determination of the MICs for 66 genotypically characterized
      Burkholderia cepacia isolates obtained from the sputum of cystic fibrosis
      patients. In vitro synergy assays, as performed by the time-kill methodology, of
      two- and three-drug combinations of the beta-lactams with tobramycin, rifampin,
      and/or ciprofloxacin were also performed with 10 strains susceptible,
      intermediate, or resistant to fluoroquinolones. On the basis of the MICs,
      meropenem and temocillin were the most active beta-lactam agents, with MICs at
      which 90% of isolates are inhibited of 8 and 32 micrograms/ml, respectively. The
      addition of ciprofloxacin significantly enhanced the killing activities of
      piperacillin, imipenem, and meropenem against the 10 strains tested (P < 0.05).
      The best killing activity was obtained with the combination of meropenem and
      ciprofloxacin, with bactericidal activity of 3.31 +/- 0.36 log10 CFU/ml (P <
      0.05). Compared to the activity of the two-drug beta-lactam-ciprofloxacin
      combination, the addition of rifampin or tobramycin did not significantly
      increase the killing activity (P > 0.05). The three-drug combinations (with or
      without ciprofloxacin) significantly enhanced the killing activities of
      piperacillin, imipenem, and meropenem relative to the activities of the beta
      lactams used alone (P < 0.05). The combination beta-lactam-ciprofloxacin
      tobramycin was the combination with the most consistently synergistic effect.

PMID- 9925509
TI  - Exposure to antibiotics induces expression of the Mycobacterium tuberculosis sigF
      gene: implications for chemotherapy against mycobacterial persistors.
AB  - The sigF gene encodes an alternate sigma factor found in Mycobacterium
      tuberculosis and related pathogenic mycobacteria. Determination of conditions of
      sigF expression is an important step in understanding the conditional gene
      regulation which may govern such processes as virulence and dormancy in
      mycobacteria. We constructed an in-frame translational lacZ-kan fusion within the
      sigF gene to determine the conditions of sigF expression. This reporter construct
      was expressed from a multicopy plasmid in a strain of BCG harboring an integrated
      luciferase reporter gene under the control of the mycobacteriophage L5 gp71
      promoter. Antibiotic exposure, in particular, ethambutol, rifampin, streptomycin,
      and cycloserine treatment, increased the level of SigF reporter specific
      expression in a dose-dependent fashion. The level of SigF reporter specific
      expression increased over 100-fold in late-stationary-phase growth compared to
      that in exponential growth. During the exponential phase, SigF specific
      expression could be induced by a number of other stresses. Anaerobic metabolism
      induced SigF by greater than 150-fold, particularly in the presence of
      metronidazole. Cold shock increased the level of SigF specific expression, while
      heat shock decreased it. Oxidative stress was also an important inducer of SigF
      specific expression; a greater induction was seen with cumene hydroperoxide than
      with hydrogen peroxide. Comparisons of bacterial viability as determined by the
      luciferase assay or by plating serial dilutions revealed that luciferase gp71
      dependent activity was an unreliable predictor of the numbers of CFU during
      stationary-phase growth and anaerobic metabolism. The induction of sigF following
      antibiotic exposure suggests that this bacterial transcription factor may control
      genes which are important for mycobacterial persistence in the host during
      chemotherapy.

PMID- 9925510
TI  - Variation in the composition and pore function of major outer membrane pore
      protein P2 of Haemophilus influenzae from cystic fibrosis patients.
AB  - We investigated the relationship between susceptibility to beta-lactam
      antibiotics and variation in the major outer membrane protein P2 (OmpP2; also
      called porin) of persistent nonencapsulated Haemophilus influenzae isolated from
      cystic fibrosis patients. Nine OmpP2 variants were selected from two distinct H.
      influenzae strains from two patients extensively treated with beta-lactam
      antibiotics. The variants differed in their susceptibilities to at least two beta
      lactam antibiotics. By detergent extraction and column chromatography, OmpP2 was
      purified from two variants that were derived from strain 70 and that differed
      notably in their susceptibilities to beta-lactam antibiotics. The proteins were
      reconstituted into black lipid membranes for measurement of porin function. OmpP2
      from the more resistant isolate (isolate 70b) had a smaller channel conductance
      than OmpP2 of the more susceptible isolate (isolate 70f). DNA sequencing of ompP2
      of these isolates revealed single nonsynonymous base differences; there were
      changes in the amino acid sequence corresponding to surface-exposed loops 4, 5,
      6, and 8. Changes in loops 4, 5, and 6 were previously shown to result in
      antigenic differences. Beside these mutations, variants of strain 70 showed
      additional mutations in loop 1 and nonexposed loop 3. Taken together, our results
      suggest that in variants of strain 70, nonsynonymous point mutations accumulated
      both in the sequences of ompP2 coding for antigen-variable loops and in other
      loops, notably, loops 1 and 3. The latter changes are suggested to affect the
      permeability of the porin channel.

PMID- 9925511
TI  - Amphotericin B and fluconazole affect cellular charge, macrophage phagocytosis,
      and cellular morphology of Cryptococcus neoformans at subinhibitory
      concentrations.
AB  - Amphotericin B (AmB) and fluconazole (FLU) are the major antifungal drugs used in
      the treatment of cryptococcosis. Both drugs are believed to exert their
      antifungal effects through actions on cell membrane sterols. In this study we
      investigated whether AmB and FLU had other, more subtle effects on C. neoformans
      that could contribute to their therapeutic efficacy. C. neoformans cells were
      grown in media with subinhibitory concentrations of either AmB or FLU and
      analyzed for cellular charge, phagocytosis by macrophages with antibody and
      complement opsonins, appearance by scanning electron and light microscopies, and
      release of the capsular polysaccharide glucuronoxylomannan into the culture
      medium. Growth in the presence of either AmB or FLU resulted in major reductions
      in cellular charge, as measured by determination of the zeta potential.
      Phagocytosis studies demonstrated that exposure of C. neoformans to subinhibitory
      concentrations of AmB or FLU enhanced phagocytosis by macrophages. Scanning
      electron microscopy revealed that a large proportion of cells had an altered
      capsular appearance. Cells grown in medium with either AmB or FLU were smaller
      and released more glucuronoxylomannan into the culture medium than cells grown
      without antibiotics. The results suggest additional mechanisms of action for AmB
      and FLU that may be operative in body compartments where drug levels do not
      achieve the MICs. Furthermore, the results suggest mechanisms by which AmB and
      FLU can cooperate with humoral and cellular immune defense systems in controlling
      C. neoformans infections.

PMID- 9925512
TI  - glmM operon and methicillin-resistant glmM suppressor mutants in Staphylococcus
      aureus.
AB  - The Staphylococcus aureus phosphoglucosamine mutase gene glmM was shown to be the
      last gene of a three-cistron operon, orf1-orf2-glmM. One transcriptional start
      was identified upstream of orf1, and a second start producing a monocistronic
      transcript was identified upstream of glmM. Disruption of glmM abolished GlmM
      production, decreased methicillin resistance, and resulted in teicoplanin
      hypersusceptibility without affecting the production of the endogenous penicillin
      binding proteins and PBP 2'. Complementation of the glmM mutation by the complete
      glmM operon restored both methicillin resistance and normal teicoplanin
      susceptibility. In contrast, a highly methicillin-resistant suppressor mutant
      obtained by selection for growth in the presence of methicillin remained GlmM
      deficient and teicoplanin hypersusceptible. The suppressor mutation was not
      linked to the glmM operon but was correlated with decreased autolysis and
      increased production of a 49-kDa protein, suggesting that there is an alternative
      pathway for glucosamine-1-phosphate synthesis in S. aureus.

PMID- 9925513
TI  - Mechanism underlying levofloxacin uptake by human polymorphonuclear neutrophils.
AB  - The mechanism of radiolabeled levofloxacin ([3H]levofloxacin) uptake by human
      polymorphonuclear neutrophils (PMNs) was investigated by a classical velocity
      centrifugation technique. PMNs were incubated with levofloxacin for 5 to 180 min
      under various conditions before centrifugation through an oil cushion.
      Radioactivity was measured in the cell pellet to determine the amount of cell
      associated drug. The uptake of levofloxacin was moderate with a cellular
      concentration/extracellular concentration ratio of about 4 to 6. Levofloxacin
      accumulated in PMNs parallel to the extracellular concentration, without
      saturation, over the range of 2.5 to 200 mg/liter (linear regression analysis: r
      = 0.92; P < 0.001). The activation energy was low (36 +/- 7.2 kJ/mol).
      Levofloxacin uptake was increased in Ca(2+)-depleted, EGTA-containing medium by
      approximately 33% (P = 0.022), while Ni2+, a Ca2+ channel inhibitor, inhibited it
      in a concentration-dependent manner, with the concentration that inhibited 50% of
      control uptake being approximately 2.65 mM. Verapamil (an L-type Ca2+ channel
      inhibitor) and other pharmacologic agents which modify Ca2+ homeostasis did not
      modify levofloxacin uptake. Interestingly, Ca2+ and Mg2+ inhibited levofloxacin
      uptake in a concentration-dependent manner. EGTA, Ni2+, and verapamil did not
      modify levofloxacin efflux; thapsigargin, a Ca2+ pool-releasing agent, modestly
      increased the intracellular retention of levofloxacin. In addition, contrary to
      other fluoroquinolones, probenecid at 1 to 10 mM did not modify either
      levofloxacin uptake or efflux. These data are consistent with a mechanism of
      passive accumulation of levofloxacin in PMNs. Extracellular Ca2+ and Mg2+ may
      influence the structural conformation of levofloxacin or the lipophilicity of PMN
      membranes, thus explaining their effect on levofloxacin uptake.

PMID- 9925514
TI  - Genetic variation and susceptibilities to protease inhibitors among subtype B and
      F isolates in Brazil.
AB  - The genetic variation of the human immunodeficiency virus type 1 (HIV-1) protease
      gene (prt) permits the classification of HIV-1 strains into five distinct
      protease subtypes, which follow the gag subtyping patterns. The susceptibilities
      of non-B-subtype strains to protease inhibitors (PIs) and other antiretroviral
      drugs remain largely unknown. Subtype F is the main non-B strain contributing to
      the Brazilian epidemic, accounting for 15 to 20% of these infections. In this
      work, we report the findings on 81 isolates from PI-naive Brazilian patients
      collected between 1993 and 1997. In addition, the relevant PI resistance
      mutations and their phenotypes were determined in vitro for 15 of these patients
      (B = 9 and F = 6). Among these, the subtype F samples evidenced high
      sensitivities in vitro to ritonavir and indinavir, with MICs at which 50 and 90%
      of the isolates are inhibited similar to those of both the Brazilian and the U.S.
      subtype B isolates. Analysis of the 81 Brazilian prt sequences demonstrated that
      the subtype F consensus sequence differs from the U.S. and Brazilian subtype B
      consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and
      L89M). The frequency of critical PI resistance substitutions (amino acid changes
      D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean,
      2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K,
      36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. These observations
      document the relative rarity of resistance to PIs in the treatment of patients
      infected with HIV-1 subtype F in South America.

PMID- 9925515
TI  - The thiocarboxanilide nonnucleoside inhibitor UC781 restores antiviral activity
      of 3'-azido-3'-deoxythymidine (AZT) against AZT-resistant human immunodeficiency
      virus type 1.
AB  - N-[4-Chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furanca rbothioamide
      (UC781) is an exceptionally potent nonnucleoside inhibitor of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We found that a 1:1
      molar combination of UC781 and 3'-azido-3'-deoxythymidine (AZT) showed high-level
      synergy in inhibiting the replication of AZT-resistant virus, implying that UC781
      can restore antiviral activity to AZT against AZT-resistant HIV-1. Neither the
      nevirapine plus AZT nor the 2',5'-bis-O-(t-butyldimethylsilyl)-3'-spiro-5"-(4"
      amino-1",2"-oxathi ole- 2",2"-dioxide plus AZT combinations had this effect.
      Studies with purified HIV-1 reverse transcriptase (from a wild type and an AZT
      resistant mutant) showed that UC781 was a potent inhibitor of the
      pyrophosphorolytic cleavage of nucleotides from the 3' end of the DNA
      polymerization primer, a process that we have proposed to be critical for the
      phenotypic expression of AZT resistance. Combinations of UC781 plus AZT did not
      act in synergy to inhibit the replication of either wild-type virus or UC781
      resistant HIV-1. Importantly, the time to the development of viral resistance to
      combinations of UC781 plus AZT is significantly delayed compared to the time to
      the development of resistance to either drug alone.

PMID- 9925516
TI  - A rapid non-culture-based assay for clinical monitoring of phenotypic resistance
      of human immunodeficiency virus type 1 to lamivudine (3TC).
AB  - Monitoring for lamivudine (3TC) resistance is important both for the clinical
      management of human immunodeficiency virus type 1 (HIV-1)-infected patients
      treated with 3TC and for surveillance of transmission of 3TC-resistant HIV-1. We
      developed a novel non-culture-based assay for the rapid analysis of phenotypic
      resistance to 3TC of HIV-1 in plasma. The assay measures the susceptibility of
      HIV-1 reverse transcriptase (RT) activity to 3TC triphosphate (3TC-TP) in plasma.
      RT detection was done by the Amp-RT assay, an ultrasensitive PCR-based RT assay.
      Under our assay conditions, we found that 5 microM 3TC-TP inhibited RT activity
      from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not
      from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance
      mutations (77L/116Y/151M or 62V/75I/77L/116Y/151M). Mixing experiments showed a
      detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV
      1. To validate the assay for the detection of phenotypic resistance of HIV-1 to
      3TC in plasma samples, HIV-1 RT in 30 plasma specimens collected from 15 patients
      before and during therapy with 3TC was tested for evidence of phenotypic
      resistance by the Amp-RT assay. The results were compared with those of genotypic
      analysis. The RT in 12 samples was found to be 3TC sensitive, while the RT in 18
      samples had evidence of phenotypic resistance. All 12 samples with 3TC-sensitive
      RT had WT genotypes at codon 184 and were retrieved before treatment with 3TC. In
      contrast, all 18 specimens with 3TC-resistant RT were posttherapy samples. This
      assay provides a simple, rapid, and reliable method for the detection of
      phenotypic resistance of HIV-1 to 3TC in plasma.

PMID- 9925517
TI  - Clinical pharmacokinetics of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5
      yl)methyl]cytosine in human immunodeficiency virus-infected patients.
AB  - The pharmacokinetics and bioavailability of 1-[((S)-2-hydroxy-2-oxo-1,4,2
      dioxaphosphorinan-5-yl)methyl]cytosi ne (cyclic HPMPC) were examined at four
      doses in 22 patients with human immunodeficiency virus infection. Two groups of
      six patients received a single dose of cyclic HPMPC at 1.5 or 3.0 mg/kg of body
      weight by each of the oral and intravenous routes in a random order with a 2-week
      washout period between administrations. Additional patients received single
      intravenous doses of cyclic HPMPC at 5.0 mg/kg (n = 6) or 7.5 mg/kg (n = 4).
      Serial serum and urine samples were collected at intervals over 24 h after
      dosing. The concentrations of cyclic HPMPC and cidofovir in serum and urine
      samples were determined by validated reverse-phase ion-pairing high-performance
      liquid chromatography methods with derivatization and fluorescence detection.
      After intravenous administration of cyclic HPMPC, concentrations of cyclic HPMPC
      declined in a biexponential manner, with a mean +/- standard deviation half-life
      of 1.09 +/- 0.12 h (n = 22). The pharmacokinetics of cyclic HPMPC were
      independent of dose over the dose range of 1.5 to 7.5 mg/kg. The total clearance
      of cyclic HPMPC from serum and the volume of distribution of intravenous cyclic
      HPMPC were 198 +/- 39.6 ml/h/kg and 338 +/- 65.1 ml/kg, respectively (n = 22).
      The renal clearance of cyclic HPMPC (132 +/- 27.3 ml/h/kg; n = 22) exceeded the
      creatinine clearance (86.2 +/- 16.3 ml/h/kg), indicating active tubular
      secretion. The cyclic HPMPC excreted in urine in 24 h accounted for 71.3% +/-
      16.0% of the administered dose. Cidofovir was formed from cyclic HPMPC in vivo
      with a time to the maximum concentration in serum of 1.64 +/- 0.23 h (n = 22).
      Cidofovir levels declined in an apparent monoexponential manner, with a mean
      terminal half-life of 3.98 +/- 1.26 h (n = 22). The cidofovir excreted in urine
      in 24 h accounted for 9.40% +/- 2.33% of the administered cyclic HPMPC dose.
      Exposure to cidofovir after intravenous administration of cyclic HPMPC was dose
      proportional and was 14.9% of that from an equivalent dose of cidofovir. The
      present study suggests that intravenous cyclic HPMPC also has a lower potential
      for nephrotoxicity in humans compared to that of intravenous cidofovir. The oral
      bioavailabilities of cyclic HPMPC were 1.76% +/- 1.48% and 3.10% +/- 1.16% with
      the administration of doses of 1.5 and 3.0 mg/kg, respectively (n = 6 per dose).
      The maximum concentrations of cyclic HPMPC in serum were 0.036 +/- 0.021 and
      0.082 +/- 0.038 microgram/ml after the oral administration of doses of 1.5 and
      3.0 mg/kg, respectively. Cidofovir reached quantifiable levels in the serum of
      only one patient for each of the 1.5- and 3.0-mg/kg oral cyclic HPMPC doses.

PMID- 9925518
TI  - Stage-specific activity of pentavalent antimony against Leishmania donovani
      axenic amastigotes.
AB  - The standard treatment of human visceral leishmaniasis involves the use of
      pentavalent antimony (SbV) compounds. In recent years increasing numbers of
      clinical failures of treatment with SbV have been reported, probably due to the
      development of parasite resistance to this compound. The mode of action and
      mechanisms of resistance to SbV have not been fully elucidated. In the present
      study an axenic amastigote culture was used to study the in vitro responses of
      Leishmania donovani to SbV. Susceptibility to both sodium stibogluconate and
      meglumine antimoniate was found to be stage specific. Amastigotes were 73 to 271
      times more susceptible to SbV than were promastigotes. As opposed to SbV,
      trivalent antimony (SbIII) was similarly toxic to both developmental stages. When
      promastigotes were transformed to amastigotes, susceptibility to meglumine
      antimoniate developed after 4 to 5 days, upon the completion of differentiation.
      In contrast, with transformation from amastigotes to promastigotes, resistance to
      meglumine antimoniate was acquired rapidly, within 24 h, before the completion of
      differentiation. The culture of promastigotes at an acidic pH (5.5) or at an
      elevated temperature (37 degrees C) alone did not lead to the appearance of SbV
      susceptibility, emphasizing the requirement of both these environmental factors
      for the development of SbV susceptibility. A previously isolated sodium
      stibogluconate (Pentostam)-resistant L. donovani mutant (Ld1S.20) is also
      resistant to meglumine antimoniate, indicating cross-resistance to SbV-containing
      compounds. In contrast, no cross-resistance was found with SbIII, suggesting a
      mechanism of SbV resistance different from that described in Leishmania
      tarentolae. These data show that L. donovani susceptibility to SbV is parasite
      intrinsic, stage specific, and macrophage independent.

PMID- 9925519
TI  - Escherichia coli ATCC 35218 as a quality control isolate for susceptibility
      testing of Haemophilus influenzae with haemophilus test medium.
AB  - Current National Committee for Clinical Laboratory Standards (NCCLS)
      susceptibility guidelines for quality control testing with Haemophilus influenzae
      do not include a beta-lactamase-producing strain that could detect the
      deterioration of the beta-lactamase inhibitor components of amoxicillin
      clavulanic acid, ampicillin-sulbactam, and piperacillin-tazobactam. The objective
      of the study was to determine if comparable quality control results for
      Escherichia coli ATCC 35218, a beta-lactamase-producing strain, would be produced
      for the three beta-lactam-beta-lactamase inhibitor agents with Haemophilus test
      medium and Mueller-Hinton medium. The criteria used in this study to determine if
      Haemophilus test medium was acceptable for quality control testing of E. coli
      ATCC 35218 was that 100% of the results obtained with an antimicrobial agent
      methodology combination needed to be within the acceptable NCCLS ranges
      established with Mueller-Hinton medium. The MIC testing results obtained by the
      broth microdilution and E-test methods with amoxicillin-clavulanic acid and
      piperacillin-tazobactam were all within the NCCLS ranges; however, the results
      obtained with ampicillin-sulbactam by both methods were not within the NCCLS
      ranges. Acceptable results were obtained by the disk diffusion methodology with
      ampicillin-sulbactam and piperacillin-tazobactam but not with amoxicillin
      clavulanic acid. When performing susceptibility testing with H. influenzae with
      the beta-lactam-beta-lactamase inhibitors, in addition to quality control testing
      with H. influenzae ATCC 49247, testing of E. coli ATCC 35218 on Haemophilus test
      medium is an effective way to monitor the beta-lactamase inhibitors in some
      antimicrobial agent-methodology combinations.

PMID- 9925520
TI  - In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa
      overexpressing the active efflux system MexA-MexB-OprM.
AB  - During a 6-month period, 21 pairs of Pseudomonas aeruginosa isolates susceptible
      (pretherapy) and resistant (posttherapy) to antipseudomonal beta-lactam
      antibiotics were isolated from hospitalized patients. In vivo emergence of beta
      lactam resistance was associated with the overexpression of AmpC beta-lactamase
      in 10 patients. In the other 11 patients, the posttherapy isolates produced only
      low, basal levels of beta-lactamase and had increased levels of resistance to a
      variety of non-beta-lactam antibiotics (e.g., quinolones, tetracyclines, and
      trimethoprim) compared with the levels of beta-lactamase production and
      resistance of their pretherapy counterparts. These data suggested the involvement
      of the MexA-MexB-OprM active efflux system in the multidrug resistance phenotype
      of the posttherapy strains. Immunoblotting of the outer membrane proteins of
      these 11 bacterial pairs with a specific polyclonal antibody raised against OprM
      demonstrated the overexpression of OprM in all the posttherapy isolates. To
      determine whether mutations in mexR, the regulator gene of the mexA-mexB-oprM
      efflux operon, could account for the overproduction of the efflux system,
      sequencing experiments were carried out with the 11 bacterial pairs. Eight
      posttherapy isolates were found to contain insertions or deletions that led to
      frameshifts in the coding sequences of mexR. Two resistant strains had point
      mutations in mexR that yielded single amino acid changes in the protein MexR,
      while another strain did not show any mutation in mexR or in the promoter region
      upstream of mexR. Introduction of a plasmid-encoded wild-type mexR gene into five
      posttherapy isolates partially restored the susceptibility of the bacteria to
      selected antibiotics. These results indicate that in the course of antimicrobial
      therapy multidrug-resistant active efflux mutants overexpressing the MexA-MexB
      OprM system may emerge as a result of mutations in the mexR gene.

PMID- 9925521
TI  - Electrolytic generation of oxygen partially explains electrical enhancement of
      tobramycin efficacy against Pseudomonas aeruginosa biofilm.
AB  - The role of electrolysis products, including protons, hydroxyl ions, reactive
      oxygen intermediates, oxygen, hydrogen, and heat, in mediating electrical
      enhancement of killing of Pseudomonas aeruginosa biofilms by tobramycin (the
      bioelectric effect) was investigated. The log reduction in biofilm viable cell
      numbers compared to the numbers for the untreated positive control effected by
      antibiotic increased from 2.88 in the absence of electric current to 5.58 in the
      presence of electric current. No enhancement of antibiotic efficacy was observed
      when the buffer composition was changed to simulate the reduced pH that prevails
      during electrolysis. Neither did stabilization of the pH during electrical
      treatment by increasing the buffer strength eliminate the bioelectric effect. The
      temperature increase measured in our experiments, less than 0.2 degree C, was far
      too small to account for the greatly enhanced antibiotic efficacy. The addition
      of sodium thiosulfate, an agent capable of rapidly neutralizing reactive oxygen
      intermediates, did not abolish electrical enhancement of killing. The bioelectric
      effect persisted when all of the ionic constituents of the medium except the two
      phosphate buffer components were omitted. This renders the possibility of
      electrochemical generation of an inhibitory ion, such as nitrite from nitrate, an
      unlikely explanation for electrical enhancement. The one plausible explanation
      for the bioelectric effect revealed by this study was the increased delivery of
      oxygen to the biofilm due to electrolysis. When gaseous oxygen was bubbled into
      the treatment chamber during exposure to tobramycin (without electric current), a
      1.8-log enhancement of killing resulted. The enhancement of antibiotic killing by
      oxygen was not due simply to physical disturbances caused by sparging the gas
      because similar delivery of gaseous hydrogen caused no enhancement whatsoever.

PMID- 9925522
TI  - Characterization and nucleotide sequence of CARB-6, a new carbenicillin
      hydrolyzing beta-lactamase from Vibrio cholerae.
AB  - A clinical strain of Vibrio cholerae non-O1 non-O139 isolated in France produced
      a new beta-lactamase with a pI of 5.35. The purified enzyme, with a molecular
      mass of 33,000 Da, was characterized. Its kinetic constants show it to be a
      carbenicillin-hydrolyzing enzyme comparable to the five previously reported CARB
      beta-lactamases and to SAR-1, another carbenicillin-hydrolyzing beta-lactamase
      that has a pI of 4.9 and that is produced by a V. cholerae strain from Tanzania.
      This beta-lactamase is designated CARB-6, and the gene for CARB-6 could not be
      transferred to Escherichia coli K-12 by conjugation. The nucleotide sequence of
      the structural gene was determined by direct sequencing of PCR-generated
      fragments from plasmid DNA with four pairs of primers covering the whole sequence
      of the reference CARB-3 gene. The gene encodes a 288-amino-acid protein that
      shares 94% homology with the CARB-1, CARB-2, and CARB-3 enzymes, 93% homology
      with the Proteus mirabilis N29 enzyme, and 86.5% homology with the CARB-4 enzyme.
      The sequence of CARB-6 differs from those of CARB-3, CARB-2, CARB-1, N29, and
      CARB-4 at 15, 16, 17, 19, and 37 amino acid positions, respectively. All these
      mutations are located in the C-terminal region of the sequence and at the surface
      of the molecule, according to the crystal structure of the Staphylococcus aureus
      PC-1 beta-lactamase.

PMID- 9925523
TI  - ParC and GyrA may be interchangeable initial targets of some fluoroquinolones in
      Streptococcus pneumoniae.
AB  - To evaluate the role of known topoisomerase IV and gyrase mutations in the
      fluoroquinolone (FQ) resistance of Streptococcus pneumoniae, we transformed
      susceptible strain R6 with PCR-generated fragments encompassing the quinolone
      resistance-determining regions (QRDRs) of parC or gyrA from different recently
      characterized FQ-resistant mutants. Considering the MICs of FQs and the GyrA
      and/or ParC mutations of the individual transformants, we found three levels of
      resistance. The first level was obtained when a single target, ParC or GyrA,
      depending on the FQ, was modified. An additional mutation(s) in a second target,
      GyrA or ParC, led to the second level. The highest increases in resistance levels
      were seen for Bay y3118 and moxifloxacin with the transformant harboring a double
      mutation in both ParC and GyrA. When a single modified target was considered,
      only the ParC mutation(s) led to an increase in the MICs of pefloxacin and
      trovafloxacin. In contrast, the GyrA or ParC mutation(s) could lead to increases
      in the MICs of ciprofloxacin, sparfloxacin, grepafloxacin, Bay y3118, and
      moxifloxacin. These results suggest that the preferential target of trovafloxacin
      and pefloxacin is ParC, whereas either ParC or GyrA may both be initial targets
      for the remaining FQs tested. The contribution of the ParC and GyrA mutations to
      efflux-mediated FQ resistance was also examined. Active efflux was responsible
      for two- to fourfold increases in the MICs of ciprofloxacin for the
      transformants, regardless of the initial FQ resistance levels of the recipients.

PMID- 9925524
TI  - Characterization of SFO-1, a plasmid-mediated inducible class A beta-lactamase
      from Enterobacter cloacae.
AB  - Enterobacter cloacae 8009 produced an inducible class A beta-lactamase which
      hydrolyzed cefotaxime efficiently. It also hydrolyzed other beta-lactams except
      cephamycins and carbapenems. The activity was inhibited by clavulanic acid and
      imipenem. The bla gene was transferable to Escherichia coli by electroporation of
      plasmid DNA. The molecular mass of the beta-lactamase was 29 kDa and its pI was
      7.3. All of these phenotypic characteristics of the enzyme except for inducible
      production resemble those of some extended-spectrum class A beta-lactamases like
      FEC-1. The gene encoding this beta-lactamase was cloned and sequenced. The
      deduced amino acid sequence of the beta-lactamase was homologous to the AmpA
      sequences of the Serratia fonticola chromosomal enzyme (96%), MEN-1 (78%),
      Klebsiella oxytoca chromosomal enzymes (77%), TOHO-1 (75%), and FEC-1 (72%). The
      conserved sequences of class A beta-lactamases, including the S-X(T)-X(S)-K
      motif, in the active site were all conserved in this enzyme. On the basis of the
      high degree of homology to the beta-lactamase of S. fonticola, the enzyme was
      named SFO-1. The ampR gene was located upstream of the ampA gene, and the AmpR
      sequence of SFO-1 had homology with the AmpR sequences of the chromosomal beta
      lactamases from Citrobacter diversus (80%), Proteus vulgaris (68%), and
      Pseudomonas aeruginosa (60%). SFO-1 was also inducible in E. coli. However, a
      transformant harboring plasmid without intact ampR produced a small amount of
      beta-lactamase constitutively, suggesting that AmpR works as an activator of ampA
      of SFO-1. This is the first report from Japan describing an inducible plasmid
      mediated class A beta-lactamase in gram-negative bacteria.

PMID- 9925525
TI  - A broad-spectrum microbicide with virucidal activity against sexually transmitted
      viruses.
AB  - Sodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic
      alcohol, possesses surfactant properties but also denatures and unfolds both
      monomeric and subunit proteins. In preliminary experiments, we demonstrated that
      SDS is a potent inactivator of herpes simplex virus type 2 and human
      immunodeficiency virus type 1 at concentrations comparable to those used for the
      surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing
      the capsid proteins of nonenveloped viruses. In this report, we demonstrate
      inactivation of rabbit, bovine, and human papillomaviruses after brief treatment
      with dilute solutions of SDS. Effective concentrations were nontoxic to rabbit
      skin and to split-thickness grafts of human foreskin epithelium. This is the
      first report of a microbicidal surfactant that will inactivate papillomaviruses.
      We propose that SDS is now a candidate microbicide for formulation and testing
      with humans.

PMID- 9925526
TI  - Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole
      and amphotericin B for treatment of histoplasmosis in immunocompetent mice.
AB  - A murine model of intratracheally induced histoplasmosis was used to evaluate a
      new triazole antifungal agent, Schering (SCH) 56592, for treatment of
      histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and
      itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth
      dilution method. The MICs at which 90% of the isolates are inhibited were for
      0.019 microgram/ml for SCH 56592, 0.5 microgram/ml for amphotericin B, and < or =
      0.019 microgram/ml for itraconazole. Survival studies were done on groups of 10
      B6C3F1 mice with a lethal inoculum of 10(5). All mice receiving 5, 1, or 0.25 mg
      of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every
      other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only
      44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal
      burden studies done in similar groups of mice with a sublethal inoculum of 10(4)
      showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen
      tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH
      56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with
      lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH
      56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were
      measured 3 and 24 h after the last dose in mice (groups of five to seven mice),
      each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75
      and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592,
      10 mg/kg/day (2.15 micrograms/ml at 3 h and 0.35 microgram/ml at 24 h); SCH
      56592, 1 mg/kg/day (0.54 microgram/ml at 3 h and none detected at 24 h);
      itraconazole, 75 mg/kg/day (22.53 micrograms/ml at 3 h and none detected at 24
      h); itraconazole, 10 mg/kg/day (1.33 micrograms/ml at 3 h and none detected at 24
      h). Confirmatory results were obtained by high-pressure liquid chromatography
      assay. These studies show SCH 56592 to be a promising candidate for studies of
      treatment of histoplasmosis in humans.

PMID- 9925527
TI  - Activities of newer fluoroquinolones against Streptococcus pneumoniae clinical
      isolates including those with mutations in the gyrA, parC, and parE loci.
AB  - Resistance to fluoroquinolone (FQ) antibiotics in Streptococcus pneumoniae has
      been attributed primarily to specific mutations in the genes for DNA gyrase (gyrA
      and gyrB) and topoisomerase IV (parC and parE). Resistance to some FQs can result
      from a single mutation in one or more of the genes encoding these essential
      enzymes. A group of 160 clinical isolates of pneumococci was examined in this
      study, including 36 ofloxacin-resistant isolates (MICs, > or = 8 micrograms/ml)
      recovered from patients in North America, France, and Belgium. The
      susceptibilities of all isolates to clinafloxacin, grepafloxacin, levofloxacin,
      sparfloxacin, and trovafloxacin were examined by the National Committee for
      Clinical Laboratory Standards reference broth microdilution and disk diffusion
      susceptibility testing methods. Among the ofloxacin-resistant strains, 32 of 36
      were also categorized as resistant to levofloxacin, 35 were resistant to
      sparfloxacin, 29 were resistant to grepafloxacin, and 19 were resistant to
      trovafloxacin. In vitro susceptibility to clinafloxacin appeared to be least
      affected by resistance to the other FQs. Eight isolates with high- and low-level
      resistance to the newer FQs were selected for DNA sequence analysis of the
      quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE.
      The DNA and the inferred amino acid sequences of the resistant strains were
      compared with the analogous sequences of reference strain S. pneumoniae ATCC
      49619 and FQ-susceptible laboratory strain R6. Reduced susceptibilities to
      grepafloxacin and sparfloxacin (MICs, 1 to 2 micrograms/ml) and trovafloxacin
      (MICs, 0.5 to 1 microgram/ml) were associated with either a mutation in parC that
      led to a single amino acid substitution (Ser-79 to Phe or Tyr) or double
      mutations that involved the genes for both GyrA (Ser-81 to Phe) and ParE (Asp-435
      to Asn). High-level resistance to all of the compounds except clinafloxacin was
      associated with two or more amino acid substitutions involving both GyrA (Ser-81
      to Phe) and ParC (Ser-79 to Phe or Ser-80 to Pro and Asp-83 to Tyr). No mutations
      were observed in the gyrB sequences of resistant strains. These data indicate
      that mutations in pneumococcal gyrA, parC, and parE genes all contribute to
      decreased susceptibility to the newer FQs, and genetic analysis of the QRDR of a
      single gene, either gyrA or parC, is not predictive of pneumococcal resistance to
      these agents.

PMID- 9925528
TI  - Effects of NorA inhibitors on in vitro antibacterial activities and
      postantibiotic effects of levofloxacin, ciprofloxacin, and norfloxacin in
      genetically related strains of Staphylococcus aureus.
AB  - NorA is a membrane-associated multidrug efflux protein that can decrease
      susceptibility to fluoroquinolones in Staphylococcus aureus. To determine the
      effect of NorA inhibition on the pharmacodynamics of fluoroquinolones, we
      evaluated the activities of levofloxacin, ciprofloxacin, and norfloxacin with and
      without various NorA inhibitors against three genetically related strains of S.
      aureus (SA 1199, the wild-type; SA 1199B, a NorA hyperproducer with a grlA
      mutation; and SA 1199-3, a strain that inducibly hyperproduces NorA) using
      susceptibility testing, time-kill curves, and postantibiotic effect (PAE)
      methods. Levofloxacin had the most potent activity against all three strains and
      was minimally affected by addition of NorA inhibitors. In contrast, reserpine,
      omeprazole, and lansoprazole produced 4-fold decreases in ciprofloxacin and
      norfloxacin MICs and MBCs for SA 1199 and 4- to 16-fold decreases for both SA
      1199B and SA 1199-3. In time-kill experiments reserpine, omeprazole, or
      lansoprazole increased levofloxacin activity against SA 1199-3 alone by 2 log10
      CFU/ml and increased norfloxacin and ciprofloxacin activities against all three
      strains by 0.5 to 4 log10 CFU/ml. Reserpine and omeprazole increased norfloxacin
      PAEs on SA 1199, SA 1199B, and SA 1199-3 from 0.9, 0.6, and 0.2 h to 2.5 to 4.5,
      1.1 to 1.3, and 0.4 to 1.1 h, respectively; similar effects were observed with
      ciprofloxacin. Reserpine and omeprazole increased the levofloxacin PAE only on SA
      1199B (from 1.6 to 5.0 and 3.1 h, respectively). In conclusion, the NorA
      inhibitors dramatically improved the activities of the more hydrophilic
      fluoroquinolones (norfloxacin and ciprofloxacin). These compounds may restore the
      activities of these fluoroquinolones against resistant strains of S. aureus or
      may potentially enhance their activities against sensitive strains.

PMID- 9925529
TI  - Pharmacokinetics of mefloquine combined with artesunate in children with acute
      falciparum malaria.
AB  - Combining artemisinin or a derivative with mefloquine increases cure rates in
      falciparum malaria patients, reduces transmission, and may slow the development
      of resistance. The combination of artesunate, given for 3 days, and mefloquine is
      now the treatment of choice for uncomplicated multidrug-resistant falciparum
      malaria acquired on the western or eastern borders of Thailand. To optimize
      mefloquine administration in this combination, a prospective study of mefloquine
      pharmacokinetics was conducted with 120 children (4 to 15 years old) with acute
      uncomplicated falciparum malaria, who were divided into four age- and sex-matched
      groups. The patients all received artesunate (4 mg/kg of body weight/day orally
      for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with
      food, (ii) a split dose (15 mg/kg on day 2 and 10 mg/kg on day 3) with food,
      (iii) a single dose (25 mg/kg) on day 0 without food, or (iv) a single dose (25
      mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2
      was associated with a mean (95% confidence interval) increase in estimated oral
      bioavailability of 72% (36 to 109%). On day 2 coadministration with food did not
      increase mefloquine absorption significantly, and there were no significant
      differences between patients receiving split- and single-dose administration. In
      combination with artesunate, mefloquine administration should be delayed until
      the second or third day after presentation.

PMID- 9925530
TI  - Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene expression
      in livers of mice infected with an HCV-vaccinia virus recombinant.
AB  - Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide.
      Current treatments are not curative for most infected individuals, and there is
      an urgent need for both novel therapeutic agents and small-animal models which
      can be used to evaluate candidate drugs. A small-animal model of HCV gene
      expression was developed with recombinant vaccinia virus vectors. VHCV-IRES
      (internal ribosome entry site) is a recombinant vaccinia viral vector containing
      the HCV 5' nontranslated region (5'-NTR) and a portion of the HCV core coding
      region fused to the firefly luciferase gene. Intraperitoneal injection of VHCV
      IRES produced high levels of luciferase activity in the livers of BALB/c mice.
      Antisense oligonucleotides complementary to the HCV 5'-NTR and translation
      initiation codon regions were then evaluated for their effects on the expression
      of these target HCV sequences in BALB/c mice infected with the vaccinia virus
      vector. Treatment of VHCV-IRES-infected mice with 20-base phosphorothioate
      oligonucleotides complementary to the sequence surrounding the HCV initiation
      codon (nucleotides 330 to 349) specifically reduced luciferase expression in the
      livers in a dose-dependent manner. Inhibition of HCV reporter gene expression in
      this small-animal model suggests that antisense oligonucleotides may provide a
      novel therapy for treatment of chronic HCV infection.

PMID- 9925531
TI  - Efflux pump-mediated quinolone resistance in Staphylococcus aureus strains wild
      type for gyrA, gyrB, grlA, and norA.
AB  - Fluoroquinolone efflux was studied in 47 Staphylococcus aureus clinical strains
      with MICs of ciprofloxacin (CFX) of < or = 2 micrograms/ml. Forty-three strains
      were wild type for gyrA, gyrB, and grlA quinolone resistance-determining regions
      and for norA and its promoter region. Forty of these strains (MICs of CFX, 0.1 to
      0.2 microgram/ml) did not show efflux of fluoroquinolones. Three strains (MICs of
      CFX, 1 to 2 micrograms/ml) showed efflux. These results suggest that efflux can
      appear in S. aureus clinical strains in the absence of mutations in norA and its
      promoter.

PMID- 9925532
TI  - Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients
      with respiratory tract infections in Spain: results of a 1-year (1996-1997)
      multicenter surveillance study. The Spanish Surveillance Group for Respiratory
      Pathogens.
AB  - A nationwide susceptibility surveillance of 1,113 Streptococcus pneumoniae
      isolates was carried out and found the following percentages of resistance:
      cefuroxime, 46%; penicillin, 37%; macrolides, 33%; aminopenicillins, 24%;
      cefotaxime, 13%; and ceftriaxone, 8%. A significant (P < 0.05) seasonality
      pattern for beta-lactam antibiotics was observed. Resistance to macrolides was
      higher (P < 0.05) in middle-ear samples. Higher percentages of resistance to
      cefuroxime and macrolides were observed among penicillin-intermediate and 
      resistant strains, whereas high frequencies of resistance to aminopenicillins and
      expanded-spectrum cephalosporins were observed only among penicillin-resistant
      strains.

PMID- 9925533
TI  - Therapeutic effects of benzoxazinorifamycin KRM-1648 administered alone or in
      combination with a half-sized secretory leukocyte protease inhibitor or the
      nonsteroidal anti-inflammatory drug diclofenac sodium against Mycobacterium avium
      complex infection in mice.
AB  - The effects of half-sized secretory leukocyte protease inhibitor or diclofenac
      sodium administered alone or in combination with the benzoxazinorifamycin KRM
      1648 on the therapeutic efficacy of KRM-1648 against Mycobacterium avium complex
      (MAC) in mice were studied. Neither of the two anti-inflammatory drugs affected
      the efficacy of KRM-1648, while they exerted significant modulating effects on
      tumor necrosis factor alpha production by MAC-infected macrophages.

PMID- 9925534
TI  - Enterococci with acquired vancomycin resistance in pigs and chickens of different
      age groups.
AB  - Results of isolation of glycopeptide-resistant enterococci from fecal samples of
      pigs and chickens were found to differ strongly depending upon the type and age
      of animals and isolation technique (direct selective plate or broth enrichment).
      Isolations were frequent in broiler chickens and in sows but rare in layer
      chickens.

PMID- 9925535
TI  - Updated sequence information for TEM beta-lactamase genes.
AB  - The sequences of the promoter regions and of the structural genes for 13
      penicillinase, extended-spectrum, and inhibitor-resistant TEM-type beta
      lactamases have been determined, and an updated blaTEM gene nomenclature is
      proposed.

PMID- 9925536
TI  - Fungal lethality, binding, and cytotoxicity of syringomycin-E.
AB  - Syringomycin-E (SE) was significantly lethal to Aspergillus and Fusarium species
      at between 1.9 and 7.8 micrograms/ml. SE complexed with the following fungal wall
      constituents (in order of binding): beta-1,3-glucan > chitin > mannan >
      ergosterol = cholesterol. Cytotoxicity in HeLa cells was proportional to the SE
      concentration, while the amount required for cytotoxicity was 3 to 20 times that
      needed to kill 95% of the fungi tested.

PMID- 9925537
TI  - Mutations in 23S rRNA in Helicobacter pylori conferring resistance to
      erythromycin do not always confer resistance to clarithromycin.
AB  - Mutations conferring resistance to erythromycin or clarithromycin in Helicobacter
      pylori were studied. Mutation A2142G was consistently associated with
      clarithromycin MIC of > 256 micrograms/ml, whereas mutants carrying A2143G had
      MICs ranging from < or = 0.016 to > 256 micrograms/ml, suggesting that additional
      factors account for the observed multiple levels of resistance to clarithromycin.

PMID- 9925538
TI  - Human herpesvirus 8 DNA load in leukocytes of human immunodeficiency virus
      infected subjects: correlation with the presence of Kaposi's sarcoma and response
      to anticytomegalovirus therapy.
AB  - Specific human herpesvirus 8 (HHV-8) DNA sequences were found in leukocytes of 12
      of 29 (41.4%) AIDS subjects with Kaposi's sarcoma (KS), whereas they were found
      in 4 of 43 (9.3%) AIDS subjects without KS (P = 0.003), although the peak HHV-8
      DNA load in PCR-positive subjects with KS (mean, 425 copies per 0.2 microgram of
      DNA) did not significantly differ from the one found in PCR-positive patients
      without KS (mean, 218 copies). The use of intravenous ganciclovir or foscarnet
      therapy to treat cytomegalovirus disease did not affect the HHV-8 DNA load in
      seven patients for whom serial samples were analyzed.

PMID- 9925539
TI  - Pharmacokinetics of the antiviral agent beta-D-2',3'-didehydro-2',3'-dideoxy-5
      fluorocytidine in rhesus monkeys.
AB  - The values of the pharmacokinetic parameters of the nucleoside antiretroviral
      agent beta-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) in rhesus
      monkeys were determined with a two-compartment model after the administration of
      a single dose. The average values for the terminal half-life, renal clearance,
      and total systemic clearance for the intravenous administration route were 3.6 h
      and 0.31 and 0.43 liter.kg-1.h-1, respectively. The oral bioavailability of D
      D4FC averaged 41%. For the intravenous administration route, 76% of the compound
      was recovered intact in the urine within 8 h, indicating that D-D4FC was
      eliminated mainly by renal excretion. D-D4FC was detected in the cerebrospinal
      fluid (CSF) at similar concentrations after administration by both the
      intravenous and oral routes. D-D4FC levels in plasma and CSF were higher than the
      median effective concentration for human immunodeficiency virus type 1 in vitro.

PMID- 9925540
TI  - Haemophilus influenzae and Moraxella catarrhalis from patients with community
      acquired respiratory tract infections: antimicrobial susceptibility patterns from
      the SENTRY antimicrobial Surveillance Program (United States and Canada, 1997).
AB  - Between February and June of 1997, a large number of community-acquired
      respiratory tract isolates of Haemophilus influenzae (n = 1,077) and Moraxella
      catarrhalis (n = 503) from 27 U.S. and 7 Canadian medical centers were
      characterized as part of the SENTRY Antimicrobial Surveillance Program. Overall
      prevalences of beta-lactamase production were 33.5% in H. influenzae and 92.2% in
      M. catarrhalis with no differences noted between isolates recovered in the United
      States and those from Canada. Among a total of 21 different antimicrobial agents
      tested, including six cephalosporins, a beta-lactamase inhibitor combination,
      three macrolides, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX),
      rifampin, chloramphenicol, five fluoroquinolones, and quinupristin-dalfopristin,
      resistance rates of > 5% with H. influenzae were observed only with cefaclor
      (12.8%) and TMP-SMX (16.2%).

PMID- 9925541
TI  - Activity of a heat-induced reformulation of amphotericin B deoxycholate
      (fungizone) against Leishmania donovani.
AB  - The heat treatment of amphotericin B deoxycholate (Fungizone), which was
      previously shown to induce superaggregation and decrease the toxicity of the drug
      to mammalian cells, increased its activity against Leishmania donovani in BALB/c
      mice, whereas it reduced its toxicity. Heat treatment preserved the activity of
      Fungizone against L. donovani HU3-infected mouse peritoneal macrophages.

PMID- 9925542
TI  - Diversification of Escherichia coli expressing an SHV-type extended-spectrum beta
      lactamase (ESBL) during a hospital outbreak: emergence of an ESBL-hyperproducing
      strain resistant to expanded-spectrum cephalosporins.
AB  - Twelve SHV-type extended-spectrum beta-lactamase (ESBL)-producing Escherichia
      coli lac mutant isolates were recovered in October 1997 from 11 patients of the
      neonatal ward in a Warsaw hospital. The outbreak was clonal; however, some of the
      isolates expressed a much higher level of resistance to several beta-lactam
      antibiotics, including expanded-spectrum cephalosporins. This phenotype has been
      attributed to beta-lactamase hyperproduction correlating with the multiplication
      of ESBL gene copies, as was demonstrated for representative isolates.

PMID- 9925543
TI  - Resistance of Pseudomonas aeruginosa to imipenem induced by eluates from
      siliconized latex urinary catheters is related to outer membrane protein
      alterations.
AB  - The activity of imipenem against Pseudomonas aeruginosa HUS-3 decreased by 16
      times in the presence of substances eluted from siliconized latex urinary
      catheters (SLUCs). SLUCs did not inactivate imipenem or increase beta-lactamase
      activity. The outer membrane of P. aeruginosa HUS-3 grown in the presence of
      eluate lacked an OprD-like protein and expressed a new 50-kDa protein. The
      decreased activity of imipenem against P. aeruginosa in the presence of SLUCs is
      related to the loss of an OprD-like protein and the expression of a new outer
      membrane protein.

PMID- 9925544
TI  - Interplay between chromosomal beta-lactamase and the MexAB-OprM efflux system in
      intrinsic resistance to beta-lactams in Pseudomonas aeruginosa.
AB  - We investigated the role of chromosomal beta-lactamase and the MexAB-OprM efflux
      system in intrinsic resistance to beta-lactams in Pseudomonas aeruginosa.
      Determination of the susceptibilities of a series of isogenic mutants with
      impaired production of the beta-lactamase and the efflux system to 16 beta
      lactams including penicillins, cephems, oxacephems, carbapenems, and a monobactam
      demonstrated that the intrinsic resistance of P. aeruginosa to most of the beta
      lactams is due to the interplay of both factors.

PMID- 9925545
TI  - Mycobacteriocidal action of exogenous nitric oxide.
AB  - We tested the hypothesis that exposure of extracellular Mycobacterium
      tuberculosis to low concentrations (< 100 ppm) of nitric oxide (NO) for short
      periods (24 h or less) will result in microbial killing. We observed that NO had
      both dose- and time-dependent cidal effects that were very significant by two-way
      analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001],
      respectively). Conceivably, extracellular bacilli in patients with pulmonary
      tuberculosis might be vulnerable to exogenous NO.

PMID- 9925546
TI  - Detection of gyrA mutations among 335 Pseudomonas aeruginosa strains isolated in
      Japan and their susceptibilities to fluoroquinolones.
AB  - gyrA point mutations in 335 clinical Pseudomonas aeruginosa isolates were
      examined mainly by nonisotopic single-strand conformation polymorphism analysis
      and direct sequencing. Seven types of missense gyrA mutations were observed in 70
      of 335 strains (20.9%), and ciprofloxacin MICs were > or = 3.13 micrograms/ml for
      63 of 70 strains (90.0%). These included two double point mutations and three
      novel mutations (Ala-67-->Ser plus Asp-87-->Gly, Ala-84-->Pro, and Gln-106-
      >Leu). Thr-83-->Ile mutants were predominantly observed (63 of 70 mutants) and
      showed high-level fluoroquinolone resistance (ciprofloxacin MIC at which 50% of
      isolates are inhibited, 25 micrograms/ml).

PMID- 9925547
TI  - Primary targets of fluoroquinolones in Streptococcus pneumoniae.
AB  - Mutants of wild-type Streptococcus pneumoniae IID553 with mutations in parC were
      obtained by selection with trovafloxacin, levofloxacin, norfloxacin, and
      ciprofloxacin. All of the parC mutants were cross-resistant to the selecting
      agents but were not resistant to gatifloxacin and sparfloxacin. On the other
      hand, gyrA mutants were isolated by selection with gatifloxacin and sparfloxacin.
      The gyrA mutants were cross-resistant to gatifloxacin and sparfloxacin but were
      not resistant to the other fluoroquinolones tested. These results suggest that in
      wild-type S. pneumoniae the primary target of trovafloxacin, levofloxacin,
      norfloxacin, and ciprofloxacin is topoisomerase IV, whereas the primary target of
      gatifloxacin and sparfloxacin is DNA gyrase.

PMID- 9925548
TI  - An alternative animal model for comparison of treatments for cryptococcal
      meningitis.
AB  - Weanling outbred rats were infected with Cryptococcus neoformans by direct
      percranial puncture and inoculation into the cranium. A lethal infection ensued.
      Treatment with LY295337, a depsipeptide with antifungal activity, was effective
      in prolonging survival and reducing fungal counts in brain tissue. Weanling rats
      are an acceptable model for the study of central nervous system infection with C.
      neoformans.

PMID- 9925549
TI  - Expression in Escherichia coli of a new multidrug efflux pump, MexXY, from
      Pseudomonas aeruginosa.
AB  - Two new genes (mexXY) similar to mexAB, mexCD, and mexEF and mediating multidrug
      resistance were cloned from the chromosome of Pseudomonas aeruginosa. Elevated
      ethidium extrusion was observed with Escherichia coli cells harboring the plasmid
      carrying mexXY. This MexXY system confers higher resistance to fluoroquinolones
      than the MexAB and MexCD systems, and E. coli ToIC or P. aeruginosa OprM is
      necessary for the function of the MexXY system.

PMID- 9925550
TI  - In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium
      falciparum in comparison with those of standard antimalarial drugs.
AB  - The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM;
      mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%)
      showed decreased susceptibility to benflumetol. Benflumetol was slightly more
      potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak
      correlations in the responses to benflumetol and pyrimethamine, chloroquine,
      amodiaquine, artemether, quinine, and pyronaridine were observed, and these
      correlations are insufficient to suggest cross-resistance. Benflumetol may be an
      important alternative drug for the treatment of chloroquine-resistant malaria.

PMID- 9925551
TI  - Comparative activities of clinafloxacin, grepafloxacin, levofloxacin,
      moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin and nonquinolones
      linozelid, quinupristin-dalfopristin, gentamicin, and vancomycin against clinical
      isolates of ciprofloxacin-resistant and -susceptible Staphylococcus aureus
      strains.
AB  - The activities of eight fluoroquinolones and linezolid, quinupristin-dalfopristin
      (Synercid), gentamicin, and vancomycin were tested against 96 ciprofloxacin
      susceptible and 205 ciprofloxacin-resistant Staphylococcus aureus strains.
      Overall, clinafloxacin, followed by moxifloxacin and trovafloxacin, was the most
      active quinolone tested. For all isolates, linezolid and quinupristin
      dalfopristin showed activities that were at least comparable to vancomycin, with
      no cross-resistance to any other test compound.

PMID- 9925552
TI  - Carbapenem activities against Pseudomonas aeruginosa: respective contributions of
      OprD and efflux systems.
AB  - While meropenem MICs were strongly influenced by the presence or absence of the
      MexAB-OprM efflux pump in both OprD-proficient and -deficient strain backgrounds,
      MICs of imipenem and of ER-35786 remained unchanged, demonstrating that meropenem
      is a substrate of MexAB-OprM but not imipenem and ER-35786. In vitro, all three
      carbapenems selected loss of OprD as a first mechanism of resistance. However, in
      an OprD-deficient background, meropenem was able to select MexAB-OprM
      overproducers as a secondary resistance mechanism, while ER-35786 selected a
      mutant cross-resistant to sparfloxacin and cefpirome.

PMID- 9925553
TI  - Italian survey on comparative levofloxacin susceptibility in 334 clinical
      isolates of Pseudomonas aeruginosa.
AB  - A national survey on susceptibility patterns of 334 Pseudomonas aeruginosa
      isolates from intensive care units and hematology and oncology wards from 13
      Italian hospitals compared the in vitro activity of levofloxacin, an injectable
      oral fluoroquinolone, to those of ciprofloxacin, ofloxacin, ceftazidime,
      imipenem, amikacin, and gentamicin. Amikacin and imipenem had the best
      susceptibility profiles. The activity of levofloxacin was superior to those of
      the other quinolones and was comparable to that of ceftazidime. The effect of
      levofloxacin in vitro on P. aeruginosa clinical isolates suggests that further
      clinical investigations are warranted.

PMID- 9925554
TI  - Biophysical characterization of fungal phytases (myo-inositol hexakisphosphate
      phosphohydrolases): molecular size, glycosylation pattern, and engineering of
      proteolytic resistance.
AB  - Phytases (myo-inositol hexakisphosphate phosphohydrolases) are found naturally in
      plants and microorganisms, particularly fungi. Interest in these enzymes has been
      stimulated by the fact that phytase supplements increase the availability of
      phosphorus in pig and poultry feed and thereby reduce environmental pollution due
      to excess phosphate excretion in areas where there is intensive livestock
      production. The wild-type phytases from six different fungi, Aspergillus niger,
      Aspergillus terreus, Aspergillus fumigatus, Emericella nidulans, Myceliophthora
      thermophila, and Talaromyces thermophilus, were overexpressed in either
      filamentous fungi or yeasts and purified, and their biophysical properties were
      compared with those of a phytase from Escherichia coli. All of the phytases
      examined are monomeric proteins. While E. coli phytase is a nonglycosylated
      enzyme, the glycosylation patterns of the fungal phytases proved to be highly
      variable, differing for individual phytases, for a given phytase produced in
      different expression systems, and for individual batches of a given phytase
      produced in a particular expression system. Whereas the extents of glycosylation
      were moderate when the fungal phytases were expressed in filamentous fungi, they
      were excessive when the phytases were expressed in yeasts. However, the different
      extents of glycosylation had no effect on the specific activity, the
      thermostability, or the refolding properties of individual phytases. When
      expressed in A. niger, several fungal phytases were susceptible to limited
      proteolysis by proteases present in the culture supernatant. N-terminal
      sequencing of the fragments revealed that cleavage invariably occurred at exposed
      loops on the surface of the molecule. Site-directed mutagenesis of A. fumigatus
      and E. nidulans phytases at the cleavage sites yielded mutants that were
      considerably more resistant to proteolytic attack. Therefore, engineering of
      exposed surface loops may be a strategy for improving phytase stability during
      feed processing and in the digestive tract.

PMID- 9925555
TI  - Biochemical characterization of fungal phytases (myo-inositol hexakisphosphate
      phosphohydrolases): catalytic properties.
AB  - Supplementation with phytase is an effective way to increase the availability of
      phosphorus in seed-based animal feed. The biochemical characteristics of an ideal
      phytase for this application are still largely unknown. To extend the biochemical
      characterization of wild-type phytases, the catalytic properties of a series of
      fungal phytases, as well as Escherichia coli phytase, were determined. The
      specific activities of the fungal phytases at 37 degreesC ranged from 23 to 196
      U. (mg of protein)-1, and the pH optima ranged from 2.5 to 7.0. When excess
      phytase was used, all of the phytases were able to release five phosphate groups
      of phytic acid (myo-inositol hexakisphosphate), which left myo-inositol 2
      monophosphate as the end product. A combination consisting of a phytase and
      Aspergillus niger pH 2.5 acid phosphatase was able to liberate all six phosphate
      groups. When substrate specificity was examined, the A. niger, Aspergillus
      terreus, and E. coli phytases were rather specific for phytic acid. On the other
      hand, the Aspergillus fumigatus, Emericella nidulans, and Myceliophthora
      thermophila phytases exhibited considerable activity with a broad range of
      phosphate compounds, including phenyl phosphate, p-nitrophenyl phosphate, sugar
      phosphates, alpha- and beta-glycerophosphates, phosphoenolpyruvate, 3
      phosphoglycerate, ADP, and ATP. Both phosphate liberation kinetics and a time
      course experiment in which high-performance liquid chromatography separation of
      the degradation intermediates was used showed that all of the myo-inositol
      phosphates from the hexakisphosphate to the bisphosphate were efficiently cleaved
      by A. fumigatus phytase. In contrast, phosphate liberation by A. niger or A.
      terreus phytase decreased with incubation time, and the myo-inositol tris- and
      bisphosphates accumulated, suggesting that these compounds are worse substrates
      than phytic acid is. To test whether broad substrate specificity may be
      advantageous for feed application, phosphate liberation kinetics were studied in
      vitro by using feed suspensions supplemented with 250 or 500 U of either A.
      fumigatus phytase or A. niger phytase (Natuphos) per kg of feed. Initially,
      phosphate liberation was linear and identical for the two phytases, but
      considerably more phosphate was liberated by the A. fumigatus phytase than by the
      A. niger phytase at later stages of incubation.

PMID- 9925556
TI  - Analysis of nifH gene pool complexity in soil and litter at a Douglas fir forest
      site in the Oregon cascade mountain range.
AB  - Nitrogen-fixing microbial populations in a Douglas fir forest on the western
      slope of the Oregon Cascade Mountain Range were analyzed. The complexity of the
      nifH gene pool (nifH is the marker gene which encodes nitrogenase reductase) was
      assessed by performing nested PCR with bulk DNA extracted from plant litter and
      soil. The restriction fragment length polymorphisms (RFLPs) of PCR products
      obtained from litter were reproducibly different than the RFLPs of PCR products
      obtained from the underlying soil. The characteristic differences were found
      during the entire sampling period between May and September. RFLP analyses of
      cloned nifH PCR products also revealed characteristic patterns for each sample
      type. Among 42 nifH clones obtained from a forest litter library nine different
      RFLP patterns were found, and among 64 nifH clones obtained from forest soil
      libraries 13 different patterns were found. Only two of the patterns were found
      in both the litter and the soil, indicating that there were major differences
      between the nitrogen-fixing microbial populations. A sequence analysis of clones
      representing the 20 distinct patterns revealed that 19 of the patterns had a
      proteobacterial origin. All of the nifH sequences obtained from the Douglas fir
      forest litter localized in a distinct phylogenetic cluster characterized by the
      nifH sequences of members of the genera Rhizobium, Sinorhizobium, and
      Azospirillum. The nifH sequences obtained from soil were found in two additional
      clusters, one characterized by sequences of members of the genera Bradyrhizobium,
      Azorhizobium, Herbaspirillum, and Thiobacillus and the other, represented by a
      single nifH clone, located between the gram-positive bacteria and the
      cyanobacteria. Our results revealed the distinctness of the nitrogen-fixing
      microbial populations in litter and soil in a Douglas fir forest; the differences
      may be related to special requirements for degradation and mineralization
      processes in the plant litter.

PMID- 9925557
TI  - Monitoring methanotrophic bacteria in hybrid anaerobic-aerobic reactors with PCR
      and a catabolic gene probe.
AB  - We attempted to mimic in small upflow anaerobic sludge bed (UASB) bioreactors the
      metabolic association found in nature between methanogens and methanotrophs. UASB
      bioreactors were inoculated with pure cultures of methanotrophs, and the
      bioreactors were operated by using continuous low-level oxygenation in order to
      favor growth and/or survival of methanotrophs. Unlike the reactors in other
      similar studies, the hybrid anaerobic-aerobic bioreactors which we used were
      operated synchronously, not sequentially. Here, emphasis was placed on monitoring
      various methanotrophic populations by using classical methods and also a PCR
      amplification assay based on the mmoX gene fragment of the soluble methane
      monooxygenase (sMMO). The following results were obtained: (i) under the
      conditions used, Methylosinus sporium appeared to survive better than
      Methylosinus trichosporium; (ii) the PCR method which we used could detect as few
      as about 2,000 sMMO gene-containing methanotrophs per g (wet weight) of granular
      sludge; (iii) inoculation of the bioreactors with pure cultures of methanotrophs
      contributed greatly to increases in the sMMO-containing population (although the
      sMMO-containing population decreased gradually with time, at the end of an
      experiment it was always at least 2 logs larger than the initial population
      before inoculation); (iv) in general, there was a good correlation between
      populations with the sMMO gene and populations that exhibited sMMO activity; and
      (v) inoculation with sMMO-positive cultures helped increase significantly the
      proportion of sMMO-positive methanotrophs in reactors, even after several weeks
      of operation under various regimes. At some point, anaerobic-aerobic bioreactors
      like those described here might be used for biodegradation of various chlorinated
      pollutants.

PMID- 9925560
TI  - Composition and enzymatic activity of the extracellular matrix secreted by
      germlings of botrytis cinerea.
AB  - Germlings of Botrytis cinerea, an important fungal pathogen of plants, produce an
      extracellular matrix (ECM), or ensheathing film, that serves, in part, in their
      attachment (R. P. Doss, et al., Appl. Environ. Microbiol. 61:260-265, 1995). The
      composition of this film has been ascertained by using samples obtained by
      growing germlings on a glass surface, removing the fungal mycelium by vigorous
      washing, and collecting the tightly attached film by scraping the substratum with
      a razor blade. Slightly over half of the dry weight of the ECM was found to be
      carbohydrates (about 20%), proteins (about 28%), and lipids (about 6%).
      Hydrolysis of the carbohydrate portion of the ECM revealed that glucose was the
      most prominent monosaccharide present, comprising about 60% of the total
      monosaccharides. Also present were mannose (about 35%) and myo-inositol (about
      5%). The proteinaceous fraction of the ECM was made up of a number of
      polypeptides separable by polyacrylamide gel electrophoresis. The lipid fraction
      of the ECM, analyzed by thin-layer chromatography, was made up of several simple
      lipid components, including free fatty acid, mono- and triacylglycerol, wax
      ester, fatty alcohol, and several unidentified components. No complex lipids were
      detected. Isolated ECM exhibited polygalacturonase and laccase activity and was
      able to catalyze the hydrolysis of p-nitrophenyl butyrate, a model substrate for
      assessing cutinase activity. Cellulase, pectin lyase, and pectin methyl esterase
      activities were noted with both heated and unheated ECM preparations. Proteinase
      activity was not detected.

PMID- 9925558
TI  - Novel interaction between laccase and cellobiose dehydrogenase during pigment
      synthesis in the white rot fungus Pycnoporus cinnabarinus.
AB  - When glucose is the carbon source, the white rot fungus Pycnoporus cinnabarinus
      produces a characteristic red pigment, cinnabarinic acid, which is formed by
      laccase-catalyzed oxidation of the precursor 3-hydroxyanthranilic acid. When P.
      cinnabarinus was grown on media containing cellobiose or cellulose as the carbon
      source, the amount of cinnabarinic acid that accumulated was reduced or, in the
      case of cellulose, no cinnabarinic acid accumulated. Cellobiose-dependent quinone
      reducing enzymes, the cellobiose dehydrogenases (CDHs), inhibited the redox
      interaction between laccase and 3-hydroxyanthranilic acid. Two distinct proteins
      were purified from cellulose-grown cultures of P. cinnabarinus; these proteins
      were designated CDH I and CDH II. CDH I and CDH II were both monomeric proteins
      and had apparent molecular weights of about 81,000 and 101,000, respectively, as
      determined by both gel filtration and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The pI values were approximately 5.9 for CDH I and 3.8 for CDH
      II. Both CDHs used several known CDH substrates as electron acceptors and
      specifically adsorbed to cellulose. Only CDH II could reduce cytochrome c. The
      optimum pH values for CDH I and CDH II were 5.5 and 4.5, respectively. In in
      vitro experiments, both enzymes inhibited laccase-mediated formation of
      cinnabarinic acid. Oxidation intermediates of 3-hydroxyanthranilic acid served as
      endogenous electron acceptors for the two CDHs from P. cinnabarinus. These
      results demonstrated that in the presence of a suitable cellulose-derived
      electron donor, CDHs can regenerate fungal metabolites oxidized by laccase, and
      they also supported the hypothesis that CDHs act as links between cellulolytic
      and ligninolytic pathways.

PMID- 9925559
TI  - Molecular analysis of ammonia-oxidizing bacteria of the beta subdivision of the
      class Proteobacteria in compost and composted materials.
AB  - Although the practice of composting animal wastes for use as biofertilizers has
      increased in recent years, little is known about the microorganisms responsible
      for the nitrogen transformations which occur in compost and during the composting
      process. Ammonia is the principle available nitrogenous compound in composting
      material, and the conversion of this compound to nitrite in the environment by
      chemolithotrophic ammonia-oxidizing bacteria is an essential step in nitrogen
      cycling. Therefore, the distribution of ammonia-oxidizing members of the beta
      subdivision of the class Proteobacteria in a variety of composting materials was
      assessed by amplifying 16S ribosomal DNA (rDNA) and 16S rRNA by PCR and reverse
      transcriptase PCR (RT-PCR), respectively. The PCR and RT-PCR products were
      separated by denaturing gradient gel electrophoresis (DGGE) and were identified
      by hybridization with a hierarchical set of oligonucleotide probes designed to
      detect ammonia oxidizer-like sequence clusters in the genera Nitrosospira and
      Nitrosomonas. Ammonia oxidizer-like 16S rDNA was detected in almost all of the
      materials tested, including industrial and experimental composts, manure, and
      commercial biofertilizers. A comparison of the DGGE and hybridization results
      after specific PCR and RT-PCR suggested that not all of the different ammonia
      oxidizer groups detected in compost are equally active. amoA, the gene encoding
      the active-site-containing subunit of ammonia monooxygenase, was also targeted by
      PCR, and template concentrations were estimated by competitive PCR. Detection of
      ammonia-oxidizing bacteria in the composts tested suggested that such materials
      may not be biologically inert with respect to nitrification and that the fate of
      nitrogen during composting and compost storage may be affected by the presence of
      these organisms.

PMID- 9925562
TI  - 1,4-benzoquinone reductase from Phanerochaete chrysosporium: cDNA cloning and
      regulation of expression.
AB  - A cDNA clone encoding a quinone reductase (QR) from the white rot basidiomycete
      Phanerochaete chrysosporium was isolated and sequenced. The cDNA consisted of
      1,007 nucleotides and a poly(A) tail and encoded a deduced protein containing 271
      amino acids. The experimentally determined eight-amino-acid N-terminal sequence
      of the purified QR protein from P. chrysosporium matched amino acids 72 to 79 of
      the predicted translation product of the cDNA. The Mr of the predicted
      translation product, beginning with Pro-72, was essentially identical to the
      experimentally determined Mr of one monomer of the QR dimer, and this finding
      suggested that QR is synthesized as a proenzyme. The results of in vitro
      transcription-translation experiments suggested that QR is synthesized as a
      proenzyme with a 71-amino-acid leader sequence. This leader sequence contains two
      potential KEX2 cleavage sites and numerous potential cleavage sites for
      dipeptidyl aminopeptidase. The QR activity in cultures of P. chrysosporium
      increased following the addition of 2-dimethoxybenzoquinone, vanillic acid, or
      several other aromatic compounds. An immunoblot analysis indicated that induction
      resulted in an increase in the amount of QR protein, and a Northern blot analysis
      indicated that this regulation occurs at the level of the qr mRNA.

PMID- 9925561
TI  - Green fluorescent protein as a noninvasive stress probe in resting Escherichia
      coli cells.
AB  - We constructed and characterized three stress probe plasmids which utilize a
      green fluorescent protein as a noninvasive reporter in order to elucidate
      Escherichia coli cellular stress responses in quiescent or resting cells.
      Cellular stress levels were easily detected by fusing three heat shock stress
      protein promoter elements, those of the heat shock transcription factor sigma32,
      the protease subunit ClpB, and the chaperone DnaK, to the reporter gene gfpuv.
      When perturbed by a chemical or physical stress (such as a heat shock, nutrient
      [amino acid] limitation, or addition of IPTG [isopropyl-beta-D
      thiogalactopyranoside], acetic acid, ethanol, phenol, antifoam, or salt [osmotic
      shock]), the E. coli cells produced GFPuv, which was easily detected within the
      cells as emitted green fluorescence. Temporal and amplitudinal mapping of the
      responses was performed, and the results revealed regions where quantitative
      delineation of cell stress was afforded.

PMID- 9925563
TI  - Quantifying microbial diversity: morphotypes, 16S rRNA genes, and carotenoids of
      oxygenic phototrophs in microbial mats.
AB  - We quantified the diversity of oxygenic phototrophic microorganisms present in
      eight hypersaline microbial mats on the basis of three cultivation-independent
      approaches. Morphological diversity was studied by microscopy. The diversity of
      carotenoids was examined by extraction from mat samples and high-pressure liquid
      chromatography analysis. The diversity of 16S rRNA genes from oxygenic
      phototrophic microorganisms was investigated by extraction of total DNA from mat
      samples, amplification of 16S rRNA gene segments from cyanobacteria and plastids
      of eukaryotic algae by phylum-specific PCR, and sequence-dependent separation of
      amplification products by denaturing-gradient gel electrophoresis. A numerical
      approach was introduced to correct for crowding the results of chromatographic
      and electrophoretic analyses. Diversity estimates typically varied up to twofold
      among mats. The congruence of richness estimates and Shannon-Weaver indices based
      on numbers and proportional abundances of unique morphotypes, 16S rRNA genes, and
      carotenoids unveiled the underlying diversity of oxygenic phototrophic
      microorganisms in the eight mat communities studied.

PMID- 9925564
TI  - Degradation of starch-poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate)
      bioplastic in tropical coastal waters.
AB  - Extruded bioplastic was prepared from cornstarch or poly(beta-hydroxybutyrate-co
      beta-hydroxyvalerate) (PHBV) or blends of cornstarch and PHBV. The blended
      formulations contained 30 or 50% starch in the presence or absence of
      polyethylene oxide (PEO), which enhances adherence of starch granules to PHBV.
      Degradation of these formulations was monitored for 1 year at four stations in
      coastal water southwest of Puerto Rico. Two stations were within a mangrove
      stand. The other two were offshore; one of these stations was on a shallow
      shoulder of a reef, and the other was at a location in deeper water. Microbial
      enumeration at the four stations revealed considerable flux in the populations
      over the course of the year. However, in general, the overall population
      densities were 1 order of magnitude less at the deeper-water station than at the
      other stations. Starch degraders were 10- to 50-fold more prevalent than PHBV
      degraders at all of the stations. Accordingly, degradation of the bioplastic, as
      determined by weight loss and deterioration of tensile properties, correlated
      with the amount of starch present (100% starch >50% starch > 30% starch > 100%
      PHBV). Incorporation of PEO into blends slightly retarded the rate of
      degradation. The rate of loss of starch from the 100% starch samples was about
      2%/day, while the rate of loss of PHBV from the 100% PHBV samples was about
      0.1%/day. Biphasic weight loss was observed for the starch-PHBV blends at all of
      the stations. A predictive mathematical model for loss of individual polymers
      from a 30% starch-70% PHBV formulation was developed and experimentally
      validated. The model showed that PHBV degradation was delayed 50 days until more
      than 80% of the starch was consumed and predicted that starch and PHBV in the
      blend had half-lives of 19 and 158 days, respectively. Consistent with the
      relatively low microbial populations, bioplastic degradation at the deeper-water
      station exhibited an initial lag period, after which degradation rates comparable
      to the degradation rates at the other stations were observed. Presumably,
      significant biodegradation occurred only after colonization of the plastic, a
      parameter that was dependent on the resident microbial populations. Therefore, it
      can be reasonably inferred that extended degradation lags would occur in open
      ocean water where microbes are sparse.

PMID- 9925566
TI  - A strategy for detection of viruses in groundwater by PCR.
AB  - We evaluated the use of the PCR for detection of enteric viruses in groundwater.
      To do this, we used an improved sample-processing technique and a large-volume
      amplification protocol. The objective of this study was to use advanced molecular
      techniques to develop a rapid and simple method which can be used by the water
      industry for detection of viral contamination in a variety of water samples. The
      strategy described here fulfills the water industry's need for a rapid, reliable,
      easily performed method for analyzing groundwater for virus contamination.
      Viruses were detected after concentration from at least 400 gallons (1,512
      liters) of water by a filter adsorption and elution method, which resulted in a
      concentrate containing viruses. A total of 150 samples were analyzed by
      performing cell culture assays for enteroviruses and by performing reverse
      transcription PCR (RT-PCR) analyses for enteroviruses, hepatitis A virus, and
      rotavirus. Thirteen samples (8.7%) produced cellular cytopathic effects when the
      Buffalo green monkey cell line was used. When primers specific for enteroviruses
      were used in RT-PCR, 40 of 133 samples (30.1%) tested positive for the presence
      of enterovirus RNA. When hepatitis A virus-specific primers were used, 12 of 139
      samples (8.6%) were considered positive for the presence of hepatitis A viral
      RNA. The RT-PCR analysis performed with rotavirus-specific primers identified 18
      of 130 samples (13.8%) that were positive for rotavirus RNA sequences. Our sample
      processing technique and large-volume PCR protocol (reaction volume, 300
      microliter) resulted in sufficient removal or dilution of inhibitors so that more
      than 95% of the samples could be assayed by PCR. Because of its sensitivity for
      detecting viral nucleic acid sequences, PCR analysis should produce more positive
      results than cell culture analysis. Since either cell culture analysis or PCR can
      reveal only a "snapshot" of the quality of the groundwater being sampled, PCR
      seems to be a desirable rapid initial screening tool.

PMID- 9925565
TI  - Anaerobic versus aerobic degradation of dimethyl sulfide and methanethiol in
      anoxic freshwater sediments.
AB  - Degradation of dimethyl sulfide and methanethiol in slurries prepared from
      sediments of minerotrophic peatland ditches were studied under various
      conditions. Maximal aerobic dimethyl sulfide-degrading capacities (4.95 nmol per
      ml of sediment slurry. h-1), measured in bottles shaken under an air atmosphere,
      were 10-fold higher than the maximal anaerobic degrading capacities determined
      from bottles shaken under N2 or H2 atmosphere (0.37 and 0. 32 nmol per ml of
      sediment slurry. h-1, respectively). Incubations under experimental conditions
      which mimic the in situ conditions (i. e., not shaken and with an air headspace),
      however, revealed that aerobic degradation of dimethyl sulfide and methanethiol
      in freshwater sediments is low due to oxygen limitation. Inhibition studies with
      bromoethanesulfonic acid and sodium tungstate demonstrated that the degradation
      of dimethyl sulfide and methanethiol in these incubations originated mainly from
      methanogenic activity. Prolonged incubation under a H2 atmosphere resulted in
      lower dimethyl sulfide degradation rates. Kinetic analysis of the data resulted
      in apparent Km values (6 to 8 microM) for aerobic dimethyl sulfide degradation
      which are comparable to those reported for Thiobacillus spp., Hyphomicrobium
      spp., and other methylotrophs. Apparent Km values determined for anaerobic
      degradation of dimethyl sulfide (3 to 8 microM) were of the same order of
      magnitude. The low apparent Km values obtained explain the low dimethyl sulfide
      and methanethiol concentrations in freshwater sediments that we reported
      previously. Our observations point to methanogenesis as the major mechanism of
      dimethyl sulfide and methanethiol consumption in freshwater sediments.

PMID- 9925567
TI  - Multiple alpha-glucoside transporter genes in brewer's yeast.
AB  - Maltose and maltotriose are the two most abundant fermentable sugars in brewer's
      wort, and the rate of uptake of these sugars by brewer's yeast can have a major
      impact on fermentation performance. In spite of this, no information is currently
      available on the genetics of maltose and maltotriose uptake in brewing strains of
      yeast. In this work, we studied 30 brewing strains of yeast (5 ale strains and 25
      lager strains) with the aim of examining the alleles of maltose and maltotriose
      transporter genes contained by them. To do this, we hybridized gene probes to
      chromosome blots. Studies performed with laboratory strains have shown that
      maltose utilization is conferred by any one of five unlinked but highly
      homologous MAL loci (MAL1 to MAL4 and MAL6). Gene 1 at each locus encodes a
      maltose transporter. All of the strains of brewer's yeast examined except two
      were found to contain MAL11 and MAL31 sequences, and only one of these strains
      lacked MAL41. MAL21 was not present in the five ale strains and 12 of the lager
      strains. MAL61 was not found in any of the yeast strains. In three of the lager
      strains, there was evidence that MAL transporter gene sequences occurred on
      chromosomes other than those known to carry MAL loci. Sequences corresponding to
      the AGT1 gene, which encodes a transporter of several alpha-glucosides, including
      maltose and maltotriose, were detected in all but one of the yeast strains.
      Homologues of AGT1 were identified in three of the lager strains, and two of
      these homologues were mapped, one to chromosome II and the other to chromosome
      XI. AGT1 appears to be a member of a family of closely related genes, which may
      have arisen in brewer's yeast in response to selective pressure.

PMID- 9925568
TI  - Toxicity, binding, and permeability analyses of four Bacillus thuringiensis Cry1
      delta-endotoxins using brush border membrane vesicles of Spodoptera exigua and
      Spodoptera frugiperda.
AB  - The binding and pore formation properties of four Bacillus thuringiensis Cry1
      toxins were analyzed by using brush border membrane vesicles from Spodoptera
      exigua and Spodoptera frugiperda, and the results were compared to the results of
      toxicity bioassays. Cry1Fa was highly toxic and Cry1Ac was nontoxic to S. exigua
      and S. frugiperda larvae, while Cry1Ca was highly toxic to S. exigua and weakly
      toxic to S. frugiperda. In contrast, Cry1Bb was active against S. frugiperda but
      only marginally active against S. exigua. Bioassays performed with iodinated
      Cry1Bb, Cry1Fa, and Cry1Ca showed that the effects of iodination on toxin
      activity were different. The toxicities of I-labeled Cry1Bb and Cry1Fa against
      Spodoptera species were significantly less than the toxicities of the unlabeled
      toxins, while Cry1Ca retained its insecticidal activity when it was labeled with
      125I. Binding assays showed that iodination prevented Cry1Fa from binding to
      Spodoptera brush border membrane vesicles. 125I-labeled Cry1Ac, Cry1Bb, and
      Cry1Ca bound with high-affinities to brush border membrane vesicles from S.
      exigua and S. frugiperda. Competition binding experiments performed with
      heterologous toxins revealed two major binding sites. Cry1Ac and Cry1Fa have a
      common binding site, and Cry1Bb, Cry1C, and Cry1Fa have a second common binding
      site. No obvious relationship between dissociation of bound toxins from brush
      border membrane vesicles and toxicity was detected. Cry1 toxins were also tested
      for the ability to alter the permeability of membrane vesicles, as measured by a
      light scattering assay. Cry1 proteins toxic to Spodoptera larvae permeabilized
      brush border membrane vesicles, but the extent of permeabilization did not
      necessarily correlate with in vivo toxicity.

PMID- 9925569
TI  - Attachment of the yeast Rhodosporidium toruloides is mediated by adhesives
      localized at sites of bud cell development.
AB  - The basidiomycetous yeast Rhodosporidium toruloides (anamorph, Rhodotorula
      glutinis) is a common phylloplane epiphyte with biocontrol potential. To
      understand how R. toruloides adheres to plant surfaces, we obtained nonadherent
      fungal mutants after chemical mutagenesis with methane-sulfonic acid ethyl ester.
      Sixteen attachment-minus (Att-) mutants were identified by three methods: (i)
      screening capsule-minus colonies for loss of adhesive ability; (ii) enrichment
      for mutants unable to attach to polystyrene; and (iii) selection for reduced
      fluorescence of fluorescein isothiocyanate-concanavalin A (Con A)-stained cells
      by fluorescence-activated cell sorting. None of the 16 mutants attached to
      polystyrene or barley leaves. The lectin Con A eliminated adhesion in all of the
      wild-type isolates tested. Hapten competition assays indicated that Con A bound
      to mannose residues on the cell surface. Adhesion of wild-type R. toruloides was
      transient; nonadhesive cells subsequently became adhesive, with bud development.
      All Att- mutants and nonattaching wild-type cells lacked polar regions that
      stained intensely with fluorescein isothiocyanate-Con A and India ink. Lectin,
      enzyme, and chemical treatments showed that the polar regions consisted of alkali
      soluble materials, including mannose residues. Tunicamycin treatment reduced wild
      type adhesion, indicating that the mannose residues could be associated with
      glycoproteins. We concluded that compounds, including mannose residues, that are
      localized at sites of bud development mediate adhesion of R. toruloides to both
      polystyrene and barley leaf surfaces.

PMID- 9925570
TI  - Genotype analysis of Escherichia coli strains isolated from children and chickens
      living in close contact.
AB  - Escherichia coli isolates from rectal swabs from 62 chickens and stools from 42
      children living in close contact with chickens on the same farms in Kiambu
      district, Kenya, were compared for their genetic relatedness. Antibiotic
      susceptibility profiles broadly categorized isolates from the children and from
      the chickens into two separate clusters: the majority (144; 85.5%) of the E. coli
      isolates from children were multidrug resistant, while the majority (216; 87.1%)
      of the E. coli isolates from chickens were either fully susceptible or resistant
      only to tetracycline. Sixty- and 100- to 110-MDA plasmids were found to encode
      the transferable resistance to co-trimoxazole and tetracycline. HindIII
      restriction endonuclease digestion of the 60- and 100- to 110-MDA plasmids
      produced four distinct patterns for isolates from children and three distinct
      patterns for isolates from chickens. XbaI digestion of genomic DNA followed by
      pulsed-field gel electrophoresis (PFGE) analysis produced 14 distinct clusters.
      There were six distinct PFGE clusters among the isolates from children, while
      among the isolates from chickens there were seven distinct clusters. Only one
      PFGE cluster contained isolates from both children and chickens, with the
      isolates displaying an approximately 60% coefficient of similarity. This study
      showed that although several different genotypes of E. coli were isolated from
      children and chickens from the same farms, the E. coli strains from these two
      sources were distinct.

PMID- 9925571
TI  - Screening, nucleotide sequence, and biochemical characterization of an esterase
      from Pseudomonas fluorescens with high activity towards lactones.
AB  - A genomic library of Pseudomonas fluorescens DSM 50106 in a lambdaRESIII phage
      vector was screened in Escherichia coli K-12 for esterase activity by using alpha
      naphthyl acetate and Fast Blue RR. A 3.2-kb DNA fragment was subcloned from an
      esterase-positive clone and completely sequenced. Esterase EstF1 was encoded by a
      999-bp open reading frame (ORF) and exhibited significant amino acid sequence
      identity with members of the serine hydrolase family. The deduced amino acid
      sequences of two other C-terminal truncated ORFs exhibited homology to a
      cyclohexanone monooxygenase and an alkane hydroxylase. However, esterase activity
      was not induced by growing of P. fluorescens DSM 50106 in the presence of several
      cyclic ketones. The esterase gene was fused to a His tag and expressed in E.
      coli. The gene product was purified by zinc ion affinity chromatography and
      characterized. Detergents had to be added for purification, indicating that the
      enzyme was membrane bound or membrane associated. The optimum pH of the purified
      enzyme was 7.5, and the optimum temperature was 43 degreesC. The showed highest
      purified enzyme activities towards lactones. The activity increased from gamma
      butyrolactone (18.1 U/mg) to epsilon-caprolactone (21.8 U/mg) to delta
      valerolactone (36.5 U/mg). The activities towards the aliphatic esters were
      significantly lower; the only exception was the activity toward ethyl caprylate,
      which was the preferred substrate.

PMID- 9925572
TI  - Manganese deficiency can replace high oxygen levels needed for lignin peroxidase
      formation by Phanerochaete chrysosporium.
AB  - The combined effects of Mn and oxygen on lignin peroxidase (LIP) activity and
      isozyme composition in Phanerochaete chrysosporium were studied by using shallow
      stationary cultures grown in the presence of limited or excess N. When no Mn was
      added, LIP was formed in both N-limited and N-excess cultures exposed to air, but
      no LIP activity was observed at Mn concentrations greater than 13 mg/liter. In
      oxygen-flushed, N-excess cultures, LIP was formed at all Mn concentrations, and
      the peak LIP activity values in the extracellular fluid were nearly identical in
      the presence of Mn concentrations ranging from 3 to 1,500 mg/liter. When the
      availability of oxygen to cultures exposed to air was increased by growing the
      fungus under nonimmersed liquid conditions, higher levels of Mn were needed to
      suppress LIP formation compared with the levels needed in shallow stationary
      cultures. The composition of LIP isozymes was affected by the levels of N and Mn.
      Addition of veratryl alcohol to cultures exposed to air did not eliminate the
      suppressive effect of Mn on LIP formation. A deficiency of Mn in N-excess
      cultures resulted in lower biomass and a lower rate of glucose consumption than
      in the presence of Mn. In addition, almost no activity of the antioxidant enzyme
      Mn superoxide dismutase was observed in Mn-deficient, N-excess cultures, but the
      activity of this enzyme increased as the Mn concentration increased from 3 to 13
      mg/liter. No Zn/Cu superoxide dismutase activity was observed in N-excess
      cultures regardless of the Mn concentration.

PMID- 9925574
TI  - Effect of acetate on molecular and physiological aspects of Clostridium
      beijerinckii NCIMB 8052 solvent production and strain degeneration.
AB  - The addition of sodium acetate to chemically defined MP2 medium was found to
      increase and stabilize solvent production and also increase glucose utilization
      by Clostridium beijerinckii NCIMB 8052. RNA and enzyme analyses indicated that
      coenzyme A (CoA) transferase was highly expressed and has higher activity in C.
      beijerinckii NCIMB 8052 grown in MP2 medium containing added sodium acetate than
      in the microorganism grown without sodium acetate. RNA analysis suggested the
      existence of a sol operon and confirmed the presence of a ptb-buk operon in C.
      beijerinckii NCIMB 8052. In addition to CoA transferase, C. beijerinckii NCIMB
      8052 grown in MP2 medium containing added acetate demonstrated higher acetate
      kinase- and butyrate kinase-specific activity than when the culture was grown in
      MP2 medium containing no added acetate. Southern blot analysis with chromosomal
      DNA isolated from solventogenic and degenerated C. beijerinckii NCIMB 8052
      indicated that C. beijerinckii NCIMB 8052 strain degeneration does not involve
      loss of the CoA transferase genes. The addition of acetate to MP2 medium may
      induce the expression of the sol operon, which ensures solvent production and
      prevents strain degeneration in C. beijerinckii NCIMB 8052.

PMID- 9925573
TI  - Effect of O-side-chain-lipopolysaccharide chemistry on metal binding.
AB  - Pseudomonas aeruginosa PAO1 produces two chemically distinct types of
      lipopolysaccharides (LPSs), termed A-band LPS and B-band LPS. The A-band O-side
      chain is electroneutral at physiological pH, while the B-band O-side chain
      contains numerous negatively charged sites due to the presence of uronic acid
      residues in the repeat unit structure. Strain PAO1 (A+ B+) and three isogenic LPS
      mutants (A+ B-, A- B+, and A- B-) were studied to determine the contribution of
      the O-side-chain portion of LPS to metal binding by the surfaces of gram-negative
      cells. Transmission electron microscopy with energy-dispersive X-ray spectroscopy
      was used to locate and analyze sites of metal deposition, while atomic absorption
      spectrophotometry and inductively coupled plasma-mass spectrometry were used to
      perform bulk quantitation of bound metal. The results indicated that cells of all
      of the strains caused the precipitation of gold as intracellular, elemental
      crystals with a d-spacing of 2.43 A. This type of precipitation has not been
      reported previously for gram-negative cells and suggests that in the organisms
      studied gold binding is not a surface-mediated event. All four strains bound
      similar amounts of copper (0.213 to 0.222 micromol/mg [dry weight] of cells) at
      the cell surface, suggesting that the major surface metal-binding sites reside in
      portions of the LPS which are common to all strains (perhaps the phosphoryl
      groups in the core-lipid A region). However, significant differences were
      observed in the abilities of strains dps89 (A- B+) and AK1401 (A+ B-) to bind
      iron and lanthanum, respectively. Strain dps89 caused the precipitation of iron
      (1.623 micromol/mg [dry weight] of cells) as an amorphous mineral phase (possibly
      iron hydroxide) on the cell surface, while strain AK1401 nucleated precipitation
      of lanthanum (0.229 micromol/mg [dry weight] of cells) as apiculate, surface
      associated crystals. Neither iron nor lanthanum precipitates were observed on the
      cells of other strains, which suggests that the combination of A-band LPS and B
      band LPS produced by a cell may result in a cell surface which promotes the
      formation of metal-rich precipitates. We therefore propose that the negatively
      charged sites located in the O-side chains are not directly responsible for the
      binding of metallic ions; however, the B-band LPS molecule as a whole may
      contribute to overall cell surface properties which favor the precipitation of
      distinct metal-rich mineral phases.

PMID- 9925575
TI  - Staphylokinase as a plasminogen activator component in recombinant fusion
      proteins.
AB  - The plasminogen activator staphylokinase (SAK) is a promising thrombolytic agent
      for treatment of myocardial infarction. It can specifically stimulate the
      thrombolysis of both erythrocyte-rich and platelet-rich clots. However, SAK lacks
      fibrin-binding and thrombin inhibitor activities, two functions which would
      supplement and potentially improve its thrombolytic potency. Creating a
      recombinant fusion protein is one approach for combining protein domains with
      complementary functions. To evaluate SAK for use in a translational fusion
      protein, both N- and C-terminal fusions to SAK were constructed by using hirudin
      as a fusion partner. Recombinant fusion proteins were secreted from Bacillus
      subtilis and purified from culture supernatants. The rate of plasminogen
      activation by SAK was not altered by the presence of an additional N- or C
      terminal protein sequence. However, cleavage at N-terminal lysines within SAK
      rendered the N-terminal fusion unstable in the presence of plasmin. The results
      of site-directed mutagenesis of lysine 10 and lysine 11 in SAK suggested that a
      plasmin-resistant variant cannot be created without interfering with the plasmin
      processing necessary for activation of SAK. Although putative plasmin cleavage
      sites are located at the C-terminal end of SAK at lysine 135 and lysine 136,
      these sites were resistant to plasmin cleavage in vitro. Therefore, C-terminal
      fusions represent stable configurations for developing improved thrombolytic
      agents based on SAK as the plasminogen activator component.

PMID- 9925577
TI  - Ethanol synthesis by genetic engineering in cyanobacteria.
AB  - Cyanobacteria are autotrophic prokaryotes which carry out oxygenic photosynthesis
      and accumulate glycogen as the major form of stored carbon. In this research, we
      introduced new genes into a cyanobacterium in order to create a novel pathway for
      fixed carbon utilization which results in the synthesis of ethanol. The coding
      sequences of pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adh) from
      the bacterium Zymomonas mobilis were cloned into the shuttle vector pCB4 and then
      used to transform the cyanobacterium Synechococcus sp. strain PCC 7942. Under
      control of the promoter from the rbcLS operon encoding the cyanobacterial
      ribulose-1, 5-bisphosphate carboxylase/oxygenase, the pdc and adh genes were
      expressed at high levels, as demonstrated by Western blotting and enzyme activity
      analyses. The transformed cyanobacterium synthesized ethanol, which diffused from
      the cells into the culture medium. As cyanobacteria have simple growth
      requirements and use light, CO2, and inorganic elements efficiently, production
      of ethanol by cyanobacteria is a potential system for bioconversion of solar
      energy and CO2 into a valuable resource.

PMID- 9925576
TI  - Diversity of free-living and attached bacteria in offshore Western Mediterranean
      waters as depicted by analysis of genes encoding 16S rRNA.
AB  - In a previous study (S. G. Acinas, F. Rodriguez-Valera, and C. Pedros-Alio, FEMS
      Microbiol. Ecol. 24:27-40, 1997), community fingerprinting by 16S rDNA
      restriction analysis applied to Mediterranean offshore waters showed that the
      free-living pelagic bacterial community was very different from the bacterial
      cells aggregated or attached to particles of more than about 8 micrometer. Here
      we have studied both assemblages at three depths (5, 50, and 400 m) by cloning
      and sequencing the 16S rDNA obtained from the same samples, and we have also
      studied the samples by scanning electron microscopy to detect morphology
      patterns. As expected, the sequences retrieved from the assemblages were very
      different. The subsample of attached bacteria contained very little diversity,
      with close relatives of a well-known species of marine bacteria, Alteromonas
      macleodii, representing the vast majority of the clones at every depth. On the
      other hand, the free-living assemblage was highly diverse and varied with depth.
      At 400 m, close relatives of cultivated gamma Proteobacteria predominated, but as
      shown by other authors, near the surface most clones were related to phylotypes
      described only by sequence, in which the alpha Proteobacteria of the SAR11
      cluster predominated. The new technique of rDNA internal spacer analysis has been
      utilized, confirming these results. Clones representative of the A. macleodii
      cluster have been completely sequenced, producing a picture that fits well with
      the idea that they could represent a genus with at least two species and with a
      characteristic depth distribution.

PMID- 9925578
TI  - Anaerobic benzene biodegradation linked to nitrate reduction.
AB  - Benzene oxidation to carbon dioxide linked to nitrate reduction was observed in
      enrichment cultures developed from soil and groundwater microcosms. Benzene
      biodegradation occurred concurrently with nitrate reduction at a constant ratio
      of 10 mol of nitrate consumed per mol of benzene degraded. Benzene biodegradation
      linked to nitrate reduction was associated with cell growth; however, the yield,
      8.8 g (dry weight) of cells per mol of benzene, was less than 15% of the
      predicted yield for benzene biodegradation linked to nitrate reduction. In
      experiments performed with [14C]benzene, approximately 92 to 95% of the label was
      recovered in 14CO2, while the remaining 5 to 8% was incorporated into the
      nonvolatile fraction (presumably biomass), which is consistent with the low
      measured yield. In benzene-degrading cultures, nitrite accumulated
      stoichiometrically as nitrate was reduced and then was slowly reduced to nitrogen
      gas. When nitrate was depleted and only nitrite remained, the rate of benzene
      degradation decreased to almost zero. Based on electron balances, benzene
      biodegradation appears to be coupled more tightly to nitrate reduction to nitrite
      than to further reduction of nitrite to nitrogen gas.

PMID- 9925579
TI  - Influence of light intensity on methanotrophic bacterial activity in Petit Saut
      Reservoir, French Guiana.
AB  - One year after impoundment in January 1994, methanotrophic bacteria in Petit Saut
      Reservoir (French Guiana) were active at the oxic-anoxic interface. This activity
      was revealed by the sudden extinction of diffusive methane emission (600 metric
      tons of CH4. day-1 for the whole lake surface area, i.e., 360 km2). Lifting of
      inhibition was suspected. After reviewing the potential inhibitors of this
      physiological guild (O2, NH4+, sulfides) and considering the similarities with
      nitrifiers, we suggest that sunlight influenced the methanotrophic bacteria. On
      the basis of phospholipid analysis, only a type II methanotrophic community was
      identified in the lake. Both growth and methanotrophic activity of an enriched
      culture, obtained in the laboratory, were largely inhibited by illumination over
      150 microeinsteins. m-2. s-1. These results were confirmed on a pure culture of
      Methylosinus trichosporium OB3B. In situ conditions showed that water
      transparency was quite stable in 1994 and 1995 and that the oxycline moved
      steadily deeper until January 1995. Considering the mean illumination profile
      during this period, we showed that removal of methanotrophic growth inhibition
      could only occur below a 2-m depth. The oxycline reached this level in October
      1994, allowing methanotrophic bacteria to develop and to consume the entire
      methane emission 4 months later.

PMID- 9925580
TI  - Production of medium-chain-length poly(3-hydroxyalkanoates) from gluconate by
      recombinant Escherichia coli.
AB  - It was shown recently that recombinant Escherichia coli, defective in the beta
      oxidation cycle and harboring a medium-chain-length (MCL) poly(3
      hydroxyalkanoate) (PHA) polymerase-encoding gene of Pseudomonas, is able to
      produce MCL PHA from fatty acids but not from sugars or gluconate (S. Langenbach,
      B. H. A. Rehm, and A. Steinbuchel, FEMS Microbiol. Lett. 150:303-309, 1997; Q.
      Ren, Ph.D. thesis, ETH Zurich, Zurich, Switzerland, 1997). In this study, we
      report the formation of MCL PHA from gluconate by recombinant E. coli. By
      introduction of genes coding for an MCL PHA polymerase and the cytosolic
      thioesterase I ('thioesterase I) into E. coli JMU193, we were able to engineer a
      pathway for the synthesis of MCL PHA from gluconate. We used two expression
      systems, i.e., the bad promoter and alk promoter, for the 'thioesterase I- and
      PHA polymerase-encoding genes, respectively, which enabled us to modulate their
      expression independently over a range of inducer concentrations, which resulted
      in a maximum MCL PHA accumulation of 2.3% of cell dry weight from gluconate. We
      found that the amount of PHA and the 'thioesterase I activity are directly
      correlated. Moreover, the polymer accumulated in the recombinant E. coli
      consisted mainly of 3-hydroxyoctanoate monomers. On the basis of our data, we
      propose an MCL PHA biosynthesis pathway scheme for recombinant E. coli JMU193,
      harboring PHA polymerase and 'thioesterase I, when grown on gluconate, which
      involves both de novo fatty acid synthesis and beta-oxidation.

PMID- 9925581
TI  - Isolation and characterization of a Mycobacterium species capable of degrading
      three- and four-ring aromatic and aliphatic hydrocarbons.
AB  - Mycobacterium sp. strain CH1 was isolated from polycyclic aromatic hydrocarbon
      (PAH)-contaminated freshwater sediments and identified by analysis of 16S rDNA
      sequences. Strain CH1 was capable of mineralizing three- and four-ring PAHs
      including phenanthrene, pyrene, and fluoranthene. In addition, strain CH1 could
      utilize phenanthrene or pyrene as a sole carbon and energy source. A lag phase of
      at least 3 days was observed during pyrene mineralization. This lag phase
      decreased to less than 1 day when strain CH1 was grown in the presence of
      phenanthrene or fluoranthene. Strain CH1 also was capable of using a wide range
      of alkanes as sole carbon and energy sources. No DNA hybridization was detected
      with the nahAc gene probe, indicating that enzymes involved in PAH metabolism are
      not related to the well-characterized naphthalene dioxygenase gene. DNA
      hybridization was not detected when the alkB gene from Pseudomonas oleovorans was
      used under high-stringency conditions. However, there was slight but detectable
      hybridization under low-stringency conditions. This suggests a distant
      relationship between genes involved in alkane oxidation.

PMID- 9925582
TI  - Production and distribution of endoglucanase, cellobiohydrolase, and beta
      glucosidase components of the cellulolytic system of Volvariella volvacea, the
      edible straw mushroom.
AB  - The edible straw mushroom, Volvariella volvacea, produces a multicomponent enzyme
      system consisting of endo-1,4-beta-glucanase, cellobiohydrolase, and beta
      glucosidase for the conversion of cellulose to glucose. The highest levels of
      endoglucanase and cellobiohydrolase were recorded in cultures containing
      microcrystalline cellulose (Avicel) or filter paper, while lower but detectable
      levels of activity were also produced on carboxymethyl cellulose, cotton wool,
      xylitol, or salicin. Biochemical analyses of different culture fractions in
      cultures exhibiting peak enzyme production revealed that most of the endoglucase
      was present either in the culture filtrate (45.8% of the total) or associated
      with the insoluble pellet fraction remaining after centrifugation of homogenized
      mycelia (32.6%). Cellobiohydrolase exhibited a similar distribution pattern, with
      58.9% of the total enzyme present in culture filtrates and 31.0% associated with
      the pellet fraction. Conversely, most beta-glucosidase activity (63.9% of the
      total) was present in extracts of fungal mycelia whereas only 9.4% was detected
      in culture filtrates. The endoglucanase and beta-glucosidase distribution
      patterns were confirmed by confocal laser scanning microscopy combined with
      immunolabelling. Endoglucanase was shown to be largely cell wall associated or
      located extracellularly, with the highest concentrations being present in a
      region 1 to 2 microm wide immediately adjacent to the outer surface of (and
      possibly including) the hyphal wall and extending 60 to 70 microm from the hyphal
      tip. Immunofluorescence patterns indicated little if any intracellular
      endoglucanase. Most beta-glucosidase was located intracellularly in the apical
      area extending 60 to 70 microm below the hyphal tip, although enzyme was also
      evident in the extracellular region extending approximately 15 microm all around
      the hyphal tip and trailing back along the length of the hypha. The regions of
      the hypha located some distance from the apical region appeared to be devoid of
      intracellular beta-glucosidase, and the enzyme appears to be associated almost
      exclusively with, or located on the outside surface of, the hyphal wall.

PMID- 9925583
TI  - High-affinity transport of choline-O-sulfate and its use as a compatible solute
      in Bacillus subtilis.
AB  - We report here that the naturally occurring choline ester choline-O-sulfate
      serves as an effective compatible solute for Bacillus subtilis, and we have
      identified a high-affinity ATP-binding cassette (ABC) transport system
      responsible for its uptake. The osmoprotective effect of this trimethylammonium
      compound closely matches that of the potent and widely employed osmoprotectant
      glycine betaine. Growth experiments with a set of B. subtilis strains carrying
      defined mutations in the glycine betaine uptake systems OpuA, OpuC, and OpuD and
      in the high-affinity choline transporter OpuB revealed that choline-O-sulfate was
      specifically acquired from the environment via OpuC. Competition experiments
      demonstrated that choline-O-sulfate functioned as an effective competitive
      inhibitor for OpuC-mediated glycine betaine uptake, with a Ki of approximately 4
      microM. Uptake studies with [1, 2-dimethyl-14C]choline-O-sulfate showed that its
      transport was stimulated by high osmolality, and kinetic analysis revealed that
      OpuC has high affinity for choline-O-sulfate, with a Km value of 4 +/- 1 microM
      and a maximum rate of transport (Vmax) of 54 +/- 3 nmol/min. mg of protein in
      cells grown in minimal medium with 0.4 M NaCl. Growth studies utilizing a B.
      subtilis mutant defective in the choline to glycine betaine synthesis pathway and
      natural abundance 13C nuclear magnetic resonance spectroscopy of whole-cell
      extracts from the wild-type strain demonstrated that choline-O-sulfate was
      accumulated in the cytoplasm and was not hydrolyzed to choline by B. subtilis. In
      contrast, the osmoprotective effect of acetylcholine for B. subtilis is dependent
      on its biotransformation into glycine betaine. Choline-O-sulfate was not used as
      the sole carbon, nitrogen, or sulfur source, and our findings thus characterize
      this choline ester as an effective compatible solute and metabolically inert
      stress compound for B. subtilis. OpuC mediates the efficient transport not only
      of glycine betaine and choline-O-sulfate but also of carnitine, crotonobetaine,
      and gamma-butyrobetaine (R. Kappes and E. Bremer, Microbiology 144:83-90, 1998).
      Thus, our data underscore its crucial role in the acquisition of a variety of
      osmoprotectants from the environment by B. subtilis.

PMID- 9925585
TI  - Hydrolysis of pork muscle sarcoplasmic proteins by lactobacillus curvatus and
      lactobacillus sake.
AB  - Lactobacillus curvatus CECT 904 and Lactobacillus sake CECT 4808 were selected on
      the basis of their proteolytic activities against synthetic substrates. Further,
      the effects of whole cells, cell extracts, and a combination of both enzymatic
      sources on muscle sarcoplasmic proteins were determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and reverse-phase high-performance liquid
      chromatography analyses. Strains of both species displayed proteinase activities
      on five sarcoplasmic proteins. The inoculation of whole cells caused a
      degradation of peptides, whereas the addition of cell extracts resulted in the
      generation of both hydrophilic and hydrophobic peptides. This phenomenon was
      remarkably more pronounced when L. curvatus was involved. Whole cells also
      consumed a great amount of free amino acids, while the addition of intracellular
      enzymes contributed to their generation. L. sake accounted for a greater release
      of free amino acids. In general, cell viability and also proteolytic events were
      promoted when cell suspensions were provided with cell extracts as an extra
      source of enzymes.

PMID- 9925586
TI  - Leaching of pyrite by acidophilic heterotrophic iron-oxidizing bacteria in pure
      and mixed cultures.
AB  - Seven strains of heterotrophic iron-oxidizing acidophilic bacteria were examined
      to determine their abilities to promote oxidative dissolution of pyrite (FeS2)
      when they were grown in pure cultures and in mixed cultures with sulfur-oxidizing
      Thiobacillus spp. Only one of the isolates (strain T-24) oxidized pyrite when it
      was grown in pyrite-basal salts medium. However, when pyrite-containing cultures
      were supplemented with 0.02% (wt/vol) yeast extract, most of the isolates
      oxidized pyrite, and one (strain T-24) promoted rates of mineral dissolution
      similar to the rates observed with the iron-oxidizing autotroph Thiobacillus
      ferrooxidans. Pyrite oxidation by another isolate (strain T-21) occurred in
      cultures containing between 0.005 and 0.05% (wt/vol) yeast extract but was
      completely inhibited in cultures containing 0.5% yeast extract. Ferrous iron was
      also needed for mineral dissolution by the iron-oxidizing heterotrophs,
      indicating that these organisms oxidize pyrite via the "indirect" mechanism.
      Mixed cultures of three isolates (strains T-21, T-23, and T-24) and the sulfur
      oxidizing autotroph Thiobacillus thiooxidans promoted pyrite dissolution; since
      neither strains T-21 and T-23 nor T. thiooxidans could oxidize this mineral in
      yeast extract-free media, this was a novel example of bacterial synergism. Mixed
      cultures of strains T-21 and T-23 and the sulfur-oxidizing mixotroph Thiobacillus
      acidophilus also oxidized pyrite but to a lesser extent than did mixed cultures
      containing T. thiooxidans. Pyrite leaching by strain T-23 grown in an organic
      compound-rich medium and incubated either shaken or unshaken was also assessed.
      The potential environmental significance of iron-oxidizing heterotrophs in
      accelerating pyrite oxidation is discussed.

PMID- 9925584
TI  - Identification and characterization of a lysis module present in a large
      proportion of bacteriophages infecting Streptococcus thermophilus.
AB  - A lysis module encoded by the temperate bacteriophage phiO1205 was identified.
      This lysis module contains a lysin gene, designated lyt51, and two putative holin
      encoding genes, designated lyt49 and lyt50. lyt51 encodes a lytic enzyme
      specifically directed against streptococcal cell walls. Similar to other phage
      encoded lysins, Lyt51 appears to have a modular design in which the N-terminal
      portion corresponds to its enzymatic activity while the C-terminal region is
      responsible for its substrate binding specificity. The two putative holin
      encoding genes, lyt49 and lyt50, located immediately upstream of lyt51, were
      identified on the basis of their homology to other identified holin-encoding
      genes. Expression of lyt49 or lyt50 in Escherichia coli was shown to cause cell
      death and leakage of the intracellular enzyme isocitrate dehydrogenase into the
      growth medium without apparent lysis of the cells. Southern blotting experiments
      demonstrated that at least one of the three components of the identified lysis
      module is present in all members of a large collection of bacteriophages,
      indicating that components of this lysis module are widespread among
      bacteriophages infecting Streptococcus thermophilus.

PMID- 9925587
TI  - Molecular analysis of expression of the lantibiotic pep5 immunity phenotype.
AB  - The lantibiotic Pep5 is produced by Staphylococcus epidermidis 5. Within its
      biosynthetic gene cluster, the immunity gene pepI, providing producer self
      protection, is localized upstream of the structural gene pepA. Pep5 production
      and the immunity phenotype have been found to be tightly coupled (M. Reis, M.
      Eschbach-Bludau, M. I. Iglesias-Wind, T. Kupke, and H.-G. Sahl, Appl. Environ.
      Microbiol. 60:2876-2883, 1994). To study this phenomenon, we analyzed pepA and
      pepI transcription and translation and constructed a number of strains containing
      various fragments of the gene cluster and expressing different levels of
      immunity. Complementation of a pepA-expressing strain with pepI in trans did not
      result in phenotypic immunity or production of PepI. On the other hand, neither
      pepA nor its product was found to be involved in immunity, since suppression of
      the translation of the pepA mRNA by mutation of the ATG start codon did not
      reduce the level of immunity. Moreover, homologous and heterologous expression of
      pepI from a xylose-inducible promoter resulted in significant Pep5 insensitivity.
      Most important for expression of the immunity phenotype was the stability of pepI
      transcripts, which in the wild-type strain, is achieved by an inverted repeat
      with a free energy of -56.9 kJ/mol, localized downstream of pepA. We performed
      site-directed mutagenesis to study the functional role of PepI and constructed
      F13D PepI, I17R PepI, and PepI 1-65; all mutants showed reduced levels of
      immunity. Western blot analysis indicated that F13D PepI and PepI 1-65 were not
      produced correctly or were partially degraded, while I17R PepI apparently was
      less efficient in providing self-protection than the wild-type PepI.

PMID- 9925588
TI  - Identification of lactic acid bacteria from chili bo, a Malaysian food
      ingredient.
AB  - Ninety-two strains of lactic acid bacteria (LAB) were isolated from a Malaysian
      food ingredient, chili bo, stored for up to 25 days at 28 degreesC with no
      benzoic acid (product A) or with 7,000 mg of benzoic acid kg-1 (product B). The
      strains were divided into eight groups by traditional phenotypic tests. A total
      of 43 strains were selected for comparison of their sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) whole-cell protein patterns with a
      SDS-PAGE database of LAB. Isolates from product A were identified as
      Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus farciminis,
      Pediococcus acidilactici, Enterococcus faecalis, and Weissella confusa. Five
      strains belonging to clusters which could not be allocated to existing species by
      SDS-PAGE were further identified by 16S rRNA sequence comparison. One strain was
      distantly related to the Lactobacillus casei/Pediococcus group. Two strains were
      related to Weissella at the genus or species level. Two other strains did not
      belong to any previously described 16S rRNA group of LAB and occupied an
      intermediate position between the L. casei/Pediococcus group and the Weissella
      group and species of Carnobacterium. The latter two strains belong to the cluster
      of LAB that predominated in product B. The incidence of new species and
      subspecies of LAB in chili bo indicate the high probability of isolation of new
      LAB from certain Southeast Asian foods. None of the isolates exhibited
      bacteriocin activity against L. plantarum ATCC 14917 and LMG 17682.

PMID- 9925589
TI  - Genetic and morphological characterization of Cladobotryum species causing cobweb
      disease of mushrooms.
AB  - Cladobotryum dendroides (= Dactylium dendroides) has hitherto been regarded as
      the major causal agent of cobweb disease of the cultivated mushroom, Agaricus
      bisporus. Nucleotide sequence data for the internal transcribed spacer (ITS)
      regions of four Cladobotryum/Hypomyces species reported to be associated with
      cobweb disease, however, indicate that the most common pathogen is now C.
      mycophilum. This cobweb pathogen varies somewhat in conidial septation from
      published descriptions of C. mycophilum and lacks the distinctive colony odor.
      ITS sequencing revealed minor nucleotide variation which split isolates of the
      pathogen into three subgroups, two comprising isolates that were sensitive to
      methylbenzimidazole carbamate (MBC) fungicides and one comprising MBC-resistant
      isolates. The MBC-resistant isolates, which were only obtained from Ireland and
      Great Britain, clustered together strongly in randomly amplified polymorphic DNA
      (RAPD) PCR analysis, suggesting that they may be clonal. The MBC-sensitive
      isolates were more diverse. A RAPD fragment of 800 to 900 bp, containing a
      microsatellite and found in the MBC-resistant isolates, also indicated their
      clonal nature; the microsatellites of these isolates contained the same number of
      GA repeats. Smaller, polymorphic microsatellites, similarly comprising GA
      repeats, in the MBC-sensitive isolates in general correlated with their
      geographic origin.

PMID- 9925590
TI  - Cold-active serine alkaline protease from the psychrotrophic bacterium Shewanella
      strain ac10: gene cloning and enzyme purification and characterization.
AB  - The gene encoding serine alkaline protease (SapSh) of the psychrotrophic
      bacterium Shewanella strain Ac10 was cloned in Escherichia coli. The amino acid
      sequence deduced from the 2,442-bp nucleotide sequence revealed that the protein
      was 814 amino acids long and had an estimated molecular weight of 85,113. SapSh
      exhibited sequence similarities with members of the subtilisin family of
      proteases, and there was a high level of conservation in the regions around a
      putative catalytic triad consisting of Asp-30, His-65, and Ser-369. The amino
      acid sequence contained the following regions which were assigned on the basis of
      homology to previously described sequences: a signal peptide (26 residues), a
      propeptide (117 residues), and an extension up to the C terminus (about 250
      residues). Another feature of SapSh is the fact that the space between His-65 and
      Ser-369 is approximately 150 residues longer than the corresponding spaces in
      other proteases belonging to the subtilisin family. SapSh was purified to
      homogeneity from the culture supernatant of E. coli recombinant cells by affinity
      chromatography with a bacitracin-Sepharose column. The recombinant SapSh (rSapSh)
      was found to have a molecular weight of about 44,000 and to be highly active in
      the alkaline region (optimum pH, around 9.0) when azocasein and synthetic
      peptides were used as substrates. rSapSh was characterized by its high levels of
      activity at low temperatures; it was five times more active than subtilisin
      Carlsberg at temperatures ranging from 5 to 15 degreesC. The activation energy
      for hydrolysis of azocasein by rSapSh was much lower than the activation energy
      for hydrolysis of azocasein by the subtilisin. However, rSapSh was far less
      stable than the subtilisin.

PMID- 9925591
TI  - Antilisterial activity of peptide AS-48 and study of changes induced in the cell
      envelope properties of an AS-48-adapted strain of Listeria monocytogenes.
AB  - The peptide AS-48 is highly active on all Listeria species. It has a bactericidal
      and bacteriolytic mode of action on Listeria monocytogenes CECT 4032, causing
      depletion of the membrane electrical potential and pH gradient. The producer
      strain Enterococcus faecalis A-48-32, releases sufficient amounts of AS-48 into
      the growth medium to suppress L. monocytogenes in cocultures at enterococcus-to
      listeria ratios above 1 at 37 degreesC or above 10 at 15 degreesC. As the
      temperature decreases, the bactericidal effects of AS-48 are less pronounced, but
      at 2.5 microgram/ml it still can inhibit the growth of listeria at 6 degreesC. AS
      48 is highly active on liquid cultures, although concentrations above 0.2
      microgram/ml are required to avoid adaptation of listeria. AS-48-adapted cells
      can be selected at low (but still inhibitory) concentrations, and they can be
      inhibited completely by AS-48 at 0.5 microgram/ml. The adaptation is lost
      gradually upon repeated subcultivation. AS48(ad) cells are cross-resistant to
      nisin and show an increased resistance to muramidases. Their fatty acid
      composition is modified: they show a much higher proportion of branched fatty
      acids as well as a higher C15:0 An-to-C17:0 An ratio. Resistance to AS-48 is also
      maintained by protoplasts from AS48(ad) cells. Electron microscopy observations
      show that the cell wall of AS48(ad) cells is thicker and less dense. The
      structure of wild-type cells is severely modified after AS-48 treatment: the cell
      wall and the cytoplasmic membrane are disorganized, and the cytoplasmic content
      is lost. Intracytoplasmic membrane vesicles are also observed when the wild-type
      strain is treated with high AS-48 concentrations.

PMID- 9925592
TI  - Effect of compressed carbon dioxide on microbial cell viability.
AB  - In order to study the influence of compressed carbon dioxide, over a range of
      pressures (1.5 to 5.5 MPa) and exposure times (up to 7 h), on the survival of
      Escherichia coli, Saccharomyces cerevisiae, and Enterococcus faecalis, a new
      pressurizable reactor system was conceived. Microbial cells were inoculated onto
      a solid hydrophilic medium and treated at room temperature; their sensitivities
      to inactivation varied greatly. The CO2 treatment had an enhanced efficiency in
      cell destruction when the pressure and the duration of exposure were increased.
      The effects of these parameters on the loss of viability was also studied by
      response-surface methodology. This study showed that a linear correlation exists
      between microbial inactivation and CO2 pressure and exposure time, and in it
      models were proposed which were adequate to predict the experimental values. The
      end point acidity was measured for all the samples in order to understand the
      mechanism of microbial inactivation. The pHs of the treated samples did not vary,
      regardless of the experimental conditions. Other parameters, such as water
      content and pressure release time, were also investigated.

PMID- 9925593
TI  - Inactivation of toluene 2-monooxygenase in Burkholderia cepacia G4 by alkynes.
AB  - High concentrations of acetylene (10 to 50% [vol/vol] gas phase) were required to
      inhibit the growth of Burkholderia cepacia G4 on toluene, while 1% (vol/vol) (gas
      phase) propyne or 1-butyne completely inhibited growth. Low concentrations of
      longer-chain alkynes (C5 to C10) were also effective inhibitors of toluene
      dependent growth, and 2- and 3-alkynes were more potent inhibitors than their 1
      alkyne counterparts. Exposure of toluene-grown B. cepacia G4 to alkynes resulted
      in the irreversible loss of toluene- and o-cresol-dependent O2 uptake activities,
      while acetate- and 3-methylcatechol-dependent O2 uptake activities were
      unaffected. Toluene-dependent O2 uptake decreased upon the addition of 1-butyne
      in a concentration- and time-dependent manner. The loss of activity followed
      first-order kinetics, with apparent rate constants ranging from 0.25 min-1 to
      2.45 min-1. Increasing concentrations of toluene afforded protection from the
      inhibitory effects of 1-butyne. Furthermore, oxygen, supplied as H2O2, was
      required for inhibition by 1-butyne. These results suggest that alkynes are
      specific, mechanism-based inactivators of toluene 2-monooxygenase in B. cepacia
      G4, although the simplest alkyne, acetylene, was relatively ineffective compared
      to longer alkynes. Alkene analogs of acetylene and propyne-ethylene and propylene
      were not inactivators of toluene 2-monooxygenase activity in B. cepacia G4 but
      were oxidized to their respective epoxides, with apparent Ks and Vmax values of
      39.7 microM and 112.3 nmol min-1 mg of protein-1 for ethylene and 32.3 microM and
      89.2 nmol min-1 mg of protein-1 for propylene.

PMID- 9925594
TI  - A mutation that improves soluble recombinant hemoglobin accumulation in
      Escherichia coli in heme excess.
AB  - High-level expression of soluble recombinant human hemoglobin (rHb) in
      Escherichia coli was obtained with several hemoglobin variants. Under identical
      conditions, two rHbs containing the Presbyterian mutation (Asn-108-->Lys) in beta
      globin accumulated to approximately twofold less soluble globin than rHbs
      containing the corresponding wild-type beta-globin subunit accumulated. The beta
      globin Providence(asp) mutation (Lys-82-->Asp) significantly improved soluble rHb
      accumulation compared to the wild-type beta-globin subunit and restored soluble
      accumulation of rHbs containing the Presbyterian mutation to wild-type levels.
      The Providenceasp substitution introduced a negatively charged residue into the
      normally cationic 2,3-bisphosphoglycerate binding pocket, potentially reducing
      the electrostatic repulsion in the absence of the polyanion. The average soluble
      globin accumulation when there was coexpression of di-alpha-globin and beta-Lys
      82-->Asp-globin (rHb9.1) and heme was present in at least a threefold molar
      excess was 36% +/- 3% of the soluble cell protein in E. coli. The average total
      accumulation (soluble globin plus insoluble globin) was 56% +/- 7% of the soluble
      cell protein. Fermentations yielded 6.0 +/- 0. 3 g of soluble rHb9.1 per liter 16
      h after induction and 6.4 +/- 0.2 g/liter 24 h after induction. The average total
      globin yield was 9.4 g/liter 16 h after induction. High-level accumulation of
      soluble rHb in E. coli depends on culture conditions, the protein sequence, and
      the molar ratio of the heme cofactor added.

PMID- 9925595
TI  - Detection of methanotrophs in groundwater by PCR.
AB  - Methanotrophic bacteria have significant potential for bioremediation, which
      would require methods for monitoring the presence and activity of these organisms
      in environmental samples. In this study, PCR was used to detect methanotrophic
      bacteria. Primers were designed on the basis of a partial sequence of pmoA, which
      encodes one of the proteins of the particulate methane monooxygenase. Specific
      amplification of a portion of pmoA was obtained with template DNA isolated from
      lab strains of methanotrophs. A pmoA product was also obtained by using DNA from
      groundwater. The identity of the PCR product was confirmed by sequencing or by
      amplification with a nested primer. Reverse transcriptase PCR detected pmoA mRNA.

PMID- 9925596
TI  - Functional analyses of the promoters in the lantibiotic mutacin II biosynthetic
      locus in Streptococcus mutans.
AB  - The lantibiotic bacteriocin mutacin II is produced by the group II Streptococcus
      mutans. The mutacin II biosynthetic locus consists of seven genes, mutR, -A, -M, 
      T, -F, -E, and -G, organized as two operons. The mutAMTFEG operon is transcribed
      from the mutA promoter 55 bp upstream of the translation start codon for MutA,
      while the mutR promoter is 76 bp upstream of the mutR structural gene. Expression
      of the mutA promoter is regulated by the components of the growth medium, while
      the mutR promoter activity does not seem to be affected by these conditions.
      Inactivation of mutR abolishes transcription of the mutA operon but does not
      affect its own promoter activity. The expressions of both mutA and mutR promoters
      are independent of the growth stage, while the production of mutacin II is only
      elevated at the early stationary phase. Taken together, these results suggest
      that expression of the mutacin operon is regulated by a complex system involving
      transcriptional and posttranscriptional or posttranslational controls.

PMID- 9925598
TI  - Influence of carbohydrate starvation and arginine on culturability and amino acid
      utilization of lactococcus lactis subsp. lactis.
AB  - Two strains of Lactococcus lactis subsp. lactis were used to determine the
      influence of lactose and arginine on viability and amino acid use during
      carbohydrate starvation. Lactose provided energy for logarithmic-phase growth,
      and amino acids such as arginine provided energy after carbohydrate exhaustion.
      Survival time, cell numbers, and ATP concentrations increased with the addition
      of arginine to the basal medium. By the onset of lactose exhaustion, the
      concentrations of glycine-valine and glutamate had decreased by as much as 67% in
      L. lactis ML3, whereas the serine concentration increased by 97% during the same
      period. When no lactose was added, the concentrations of these amino acids
      remained constant. Similar trends were observed for L. lactis 11454. Without
      lactose or arginine, L. lactis ML3 was nonculturable on agar but was viable after
      2 days, as measured by fluorescent viability stains and intracellular ATP levels.
      However, L. lactis 11454 without lactose or arginine remained culturable for at
      least 14 days. These data suggest that lactococci become viable but nonculturable
      in response to carbohydrate depletion. Additionally, these data indicate that
      amino acids other than arginine facilitate the survival of L. lactis during
      carbohydrate starvation.

PMID- 9925597
TI  - Characterization of fatty acid composition, spore germination, and thermal
      resistance in a nisin-resistant mutant of Clostridium botulinum 169B and in the
      wild-type strain.
AB  - The membrane fatty acids, thermal resistance, and germination of a nisin
      resistant (Nisr) mutant of Clostridium botulinum 169B were compared with those of
      the wild-type (WT) strain. In the membranes of WT cells, almost 50% of the total
      fatty acids were unsaturated, but in those of Nisr cells, only 23% of the fatty
      acids were unsaturated. WT and Nisr spores contained similar amounts
      (approximately 23%) of unsaturated fatty acids, but the saturated straight
      chain/branched-chain ratio was significantly higher in Nisr spores than in WT
      spores. These fatty acid differences suggest that Nisr cell and spore membranes
      may be more rigid, a characteristic which would interfere with the pore-forming
      ability of nisin. Nisr C. botulinum did not produce an extracellular nisin
      degrading enzyme, nor were there any differences in the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis patterns of coat proteins extracted from WT
      and Nisr spores, eliminating these as possible reasons for nisin resistance. Nisr
      spores had thermal resistance parameters similar to those of WT spores. In WT
      spores, but not in Nisr spores, nisin caused a 40% reduction in thermal
      resistance and a twofold increase in the germination rate. Because the nisin
      induced increase in the germination rate of WT spores occurred only in the
      presence of a germinant (a molecule that triggers germination), nisin can be
      classified as a progerminant (a molecule that stimulates germination only in the
      presence of a germinant).

PMID- 9925599
TI  - De novo synthesis of 4,5-dimethoxycatechol and 2, 5-dimethoxyhydroquinone by the
      brown rot fungus Gloeophyllum trabeum.
AB  - The new dimethoxycatechol 4,5-dimethoxy-1,2-benzenediol (DMC) and the new
      dimethoxyhydroquinone 2,5-dimethoxy-1,4-benzenediol (DMH) were isolated from
      stationary cultures of the brown rot fungus Gloeophyllum trabeum growing on a
      glucose mineral medium protected from light. The structure was elucidated by gas
      chromatography-mass spectrometry through comparison to a synthetic standard.
      Further confirmation was obtained by forming a dimethoxyoxazole derivative by
      condensation of DMC with methylene chloride and through examination of methylated
      derivatives. DMC and DMH may serve as ferric chelators, oxygen-reducing agents,
      and redox-cycling molecules, which would include functioning as electron
      transport carriers to Fenton's reactions. Thus, they appear to be important
      components of the brown rot decay system of the fungus.

PMID- 9925600
TI  - Genetic evidence that high noninduced maltase and maltose permease activities,
      governed by MALx3-encoded transcriptional regulators, determine efficiency of gas
      production by baker's yeast in unsugared dough.
AB  - Strain selection and improvement in the baker's yeast industry have aimed to
      increase the speed of maltose fermentation in order to increase the leavening
      activity of industrial baking yeast. We identified two groups of baker's strains
      of Saccharomyces cerevisiae that can be distinguished by the mode of regulation
      of maltose utilization. One group (nonlagging strains), characterized by rapid
      maltose fermentation, had at least 12-fold more maltase and 130-fold-higher
      maltose permease activities than maltose-lagging strains in the absence of
      inducing sugar (maltose) and repressing sugar (glucose). Increasing the
      noninduced maltase activity of a lagging strain 13-fold led to an increase in CO2
      production in unsugared dough. This increase in CO2 production also was seen when
      the maltose permease activity was increased 55-fold. Only when maltase and
      maltose permease activities were increased in concert was CO2 production by a
      lagging strain similar to that of a nonlagging strain. The noninduced activities
      of maltase and maltose permease constitute the largest determinant of whether a
      strain displays a nonlagging or a lagging phenotype and are dependent upon the
      MALx3 allele. Previous strategies for strain improvement have targeted glucose
      derepression of maltase and maltose permease expression. Our results suggest that
      increasing noninduced maltase and maltose permease levels is an important target
      for improved maltose metabolism in unsugared dough.

PMID- 9925602
TI  - Purification and properties of a xylan-binding endoxylanase from Alkaliphilic
      bacillus sp. strain K-1.
AB  - An alkaliphilic bacterium, Bacillus sp. strain K-1, produces extracellular
      xylanolytic enzymes such as xylanases, beta-xylosidase, arabinofuranosidase, and
      acetyl esterase when grown in xylan medium. One of the extracellular xylanases
      that is stable in an alkaline state was purified to homogeneity by affinity
      adsorption-desorption on insoluble xylan. The enzyme bound to insoluble xylan but
      not to crystalline cellulose. The molecular mass of the purified xylan-binding
      xylanase was estimated to be approximately 23 kDa. The enzyme was stable at
      alkaline pHs up to 12. The optimum temperature and optimum pH of the enzyme
      activity were 60 degrees C and 5.5, respectively. Metal ions such as Fe2+, Ca2+,
      and Mg2+ greatly increased the xylanase activity, whereas Mn2+ strongly inhibited
      it. We also demonstrated that the enzyme could hydrolyze the raw lignocellulosic
      substances effectively. The enzymatic products of xylan hydrolysis were a series
      of short-chain xylooligosaccharides, indicating that the enzyme was an
      endoxylanase.

PMID- 9925601
TI  - LlaFI, a type III restriction and modification system in Lactococcus lactis.
AB  - We describe a type III restriction and modification (R/M) system, LlaFI, in
      Lactococcus lactis. LlaFI is encoded by a 12-kb native plasmid, pND801, harbored
      in L. lactis LL42-1. Sequencing revealed two adjacent open reading frames (ORFs).
      One ORF encodes a 680-amino-acid polypeptide, and this ORF is followed by a
      second ORF which encodes an 873-amino-acid polypeptide. The two ORFs appear to be
      organized in an operon. A homology search revealed that the two ORFs exhibited
      significant similarity to type III restriction (Res) and modification (Mod)
      subunits. The complete amino acid sequence of the Mod subunit of LlaFI was
      aligned with the amino acid sequences of four previously described type III
      methyltransferases. Both the N-terminal regions and the C-terminal regions of the
      Mod proteins are conserved, while the central regions are more variable. An S
      adenosyl methionine (Ado-Met) binding motif (present in all adenine
      methyltransferases) was found in the N-terminal region of the Mod protein. The
      seven conserved helicase motifs found in the previously described type III R/M
      systems were found at the same relative positions in the LlaFI Res sequence.
      LlaFI has cofactor requirements for activity that are characteristic of the
      previously described type III enzymes. ATP and Mg2+ are required for
      endonucleolytic activity; however, the activity is not strictly dependent on the
      presence of Ado-Met but is stimulated by it. To our knowledge, this is the first
      type III R/M system that has been characterized not just in lactic acid bacteria
      but also in gram-positive bacteria.

PMID- 9925603
TI  - Chemical and sensory changes associated with microbial flora of Mediterranean
      boque (Boops boops) stored aerobically at 0, 3, 7, and 10 degreesC.
AB  - The development of a microbial population and changes in the physicochemical and
      sensorial characteristics of Mediterranean boque (Boops boops), called gopa in
      Greece, stored aerobically at 0, 3, 7, and 10 degreesC were studied. Pseudomonads
      and Shewanella putrefaciens were the dominant bacteria at the end of the storage
      period, regardless of the temperature tested. Enterobacteria and Brochothrix
      thermosphacta also grew, but their population density was always 2 to 3 log10 CFU
      g-1 less than that of pseudomonads. The concentration of potential indicators of
      spoilage, glucose and lactic acid, decreased while that of the alpha-amino groups
      increased during storage. The concentrations of these carbon sources also
      decreased on sterile fish blocks inoculated with strains isolated from fish
      microbial flora. The organic acid profile of sterile fish blocks inoculated with
      the above-mentioned bacteria and that of naturally spoiled fish differed
      significantly. An excellent correlation (r = -0.96) between log10 counts of S.
      putrefaciens or Pseudomonas bacteria with freshness was observed in this study.

PMID- 9925604
TI  - Characteristics of garden dormice that contribute to their capacity as reservoirs
      for lyme disease spirochetes.
AB  - To describe the contribution of garden dormice to the epizootiology of Lyme
      disease, we compared their reservoir capacity for these pathogens to that of
      other sympatric hosts. Garden dormice are trapped most abundantly during early
      spring and again during midsummer, when their offspring forage. They are closely
      associated with moist forests. Garden dormice serve as hosts to nymphal ticks far
      more frequently than do other small mammals. Spirochetal infection is most
      prevalent in dormice, and many more larval ticks acquire infection in the course
      of feeding on these than on other rodents in the study site. Mature dormice
      appear to contribute more infections to the vector population than juveniles do.
      Replete larval ticks generally detach while their dormouse hosts remain within
      their nests. The population of garden dormice contributes five- to sevenfold more
      infections to the vector population than the mouse population does. Their
      competence, nymphal feeding density, and preference for a tick-permissive habitat
      combine to favor garden dormice over other putative reservoir hosts of Lyme
      disease spirochetes.

PMID- 9925605
TI  - Purification and characterization of a novel 5-oxoprolinase (without ATP
      hydrolyzing activity) from Alcaligenes faecalis N-38A.
AB  - A novel type of 5-oxoprolinase was found in a cell extract of strain N-38A, which
      was later identified as Alcaligenes faecalis. The enzyme in the cell extract was
      purified to a homogeneous state with a yield of 16.6%. The molecular weight of
      the purified enzyme was estimated to be 47,000 by both sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and gel filtration, suggesting that the enzyme
      is a monomeric protein. The enzyme specifically catalyzed a decyclization of L
      pyroglutamate without hydrolyzing ATP and also without any requirements for metal
      ions such as Mg2+ and K+. The optimal pH for the decyclization was 7.4. The
      reaction was reversible. The equilibrium constant of the reaction, Keq = [L
      glutamate]/[L-pyroglutamate], was evaluated to be approximately 0. 035, which
      indicates that the reaction tends to form L-pyroglutamate. The amino-terminal
      amino acid sequence of the enzyme was H-Glu-Pro-Arg-Leu-Asp-Thr-Ser-Gln-Leu-Tyr
      Ala-Asp-Val-His-Phe-. No protein with a similar sequence was found in the DNASIS
      database. Based on these data, it was strongly suggested that the enzyme
      described here is a novel type of 5-oxoprolinase.

PMID- 9925606
TI  - Diversity of arbuscular mycorrhizal fungus populations in heavy-metal
      contaminated soils.
AB  - High concentrations of heavy metals have been shown to adversely affect the size,
      diversity, and activity of microbial populations in soil. The aim of this work
      was to determine how the diversity of arbuscular mycorrhizal (AM) fungi is
      affected by the addition of sewage-amended sludge containing heavy metals in a
      long-term experiment. Due to the reduced number of indigenous AM fungal (AMF)
      propagules in the experimental soils, several host plants with different life
      cycles were used to multiply indigenous fungi. Six AMF ecotypes were found in the
      experimental soils, showing consistent differences with regard to their tolerance
      to the presence of heavy metals. AMF ecotypes ranged from very sensitive to the
      presence of metals to relatively tolerant to high rates of heavy metals in soil.
      Total AMF spore numbers decreased with increasing amounts of heavy metals in the
      soil. However, species richness and diversity as measured by the Shannon-Wiener
      index increased in soils receiving intermediate rates of sludge contamination but
      decreased in soils receiving the highest rate of heavy-metal-contaminated sludge.
      Relative densities of most AMF species were also significantly influenced by soil
      treatments. Host plant species exerted a selective influence on AMF population
      size and diversity. We conclude based on the results of this study that size and
      diversity of AMF populations were modified in metal-polluted soils, even in those
      with metal concentrations that were below the upper limits accepted by the
      European Union for agricultural soils.

PMID- 9925608
TI  - Estimating bacterial growth parameters by means of detection times.
AB  - We developed a new numerical method to estimate bacterial growth parameters by
      means of detection times generated by different initial counts. The observed
      detection times are subjected to a transformation involving the (unknown) maximum
      specific growth rate and the (known) ratios between the different inoculum sizes
      and the constant detectable level of counts. We present an analysis of variance
      (ANOVA) protocol based on a theoretical result according to which, if the
      specific rate used for the transformation is correct, the transformed values are
      scattered around the same mean irrespective of the original inoculum sizes. That
      mean, termed the physiological state of the inoculum, alpha, and the maximum
      specific growth rate, mu, can be estimated by minimizing the variance ratio of
      the ANOVA procedure. The lag time of the population can be calculated as lambda =
      -ln alpha/mu; i.e. the lag is inversely proportional to the maximum specific
      growth rate and depends on the initial physiological state of the population. The
      more accurately the cell number at the detection level is known, the better the
      estimate for the variance of the lag times of the individual cells.

PMID- 9925607
TI  - The chlorocatechol-catabolic transposon Tn5707 of Alcaligenes eutrophus NH9,
      carrying a gene cluster highly homologous to that in the 1,2,4-trichlorobenzene
      degrading bacterium Pseudomonas sp. strain P51, confers the ability to grow on 3
      chlorobenzoate.
AB  - Alcaligenes eutrophus (Ralstonia eutropha) NH9, isolated in Japan, utilizes 3
      chlorobenzoate as its sole source of carbon and energy. Sequencing of the
      relevant region of plasmid pENH91 from strain NH9 revealed that the genes for the
      catabolic enzymes were homologous to the genes of the modified ortho-cleavage
      pathway. The genes from strain NH9 (cbnR-ABCD) showed the highest homology (89 to
      100% identity at the nucleotide level) to the tcbR-CDEF genes on plasmid pP51 of
      the 1,2,4-trichlorobenzene-degrading bacterium Pseudomonas sp. strain P51, which
      was isolated in The Netherlands. The structure of the operon, including the
      lengths of open reading frames and intervening sequences, was completely
      conserved between the cbn and tcb genes. Most nucleotide substitutions were
      localized within and proximal to the cbnB (tcbD) gene. The difference in the
      chloroaromatics that the two strains could use as growth substrates seemed to be
      due to differences in enzymes that convert substrates to chlorocatechols. The
      restriction map of plasmid pENH91 was clearly different from that of pP51 except
      in the regions that contained the cbnR-ABCD and tcbR-CDEF genes, respectively,
      suggesting that the chlorocatechol gene clusters might have been transferred as
      units. Two homologous sequences, present as direct repeats in both flanking
      regions of the cbnR-ABCD genes on pENH91, were found to be identical insertion
      sequences (ISs), designated IS1600, which formed a composite transposon
      designated Tn5707. Although the tcbR-CDEF genes were not associated with similar
      ISs, a DNA fragment homologous to IS1600 was cloned from the chromosome of strain
      P51. The sequence of the fragment suggested that it might be a remnant of an IS.
      The two sequences, together with IS1326 and nmoT, formed a distinct cluster on a
      phylogenetic tree of the IS21 family. The diversity of the sources of these IS or
      IS-like elements suggests the prevalence of ISs of this type.

PMID- 9925609
TI  - Role of microcystins in poisoning and food ingestion inhibition of Daphnia
      galeata caused by the cyanobacterium Microcystis aeruginosa.
AB  - The effects of microcystins on Daphnia galeata, a typical filter-feeding grazer
      in eutrophic lakes, were investigated. To do this, the microcystin-producing wild
      type strain Microcystis aeruginosa PCC7806 was compared with a mcy- PCC7806
      mutant, which could not synthesize any variant of microcystin due to mutation of
      a microcystin synthetase gene. The wild-type strain was found to be poisonous to
      D. galeata, whereas the mcy- mutant did not have any lethal effect on the
      animals. Both variants of PCC7806 were able to reduce the Daphnia ingestion rate.
      Our results suggest that microcystins are the most likely cause of the daphnid
      poisoning observed when wild-type strain PCC7806 is fed to the animals, but these
      toxins are not responsible for inhibition of the ingestion process.

PMID- 9925610
TI  - Control of flavor development in wine during and after malolactic fermentation by
      Oenococcus oeni.
AB  - During malolactic fermentation in wine by Oenococcus oeni, the degradation of
      citric acid was delayed compared to the degradation of malic acid. The maximum
      concentration of diacetyl, an intermediary compound in the citric acid metabolism
      with a buttery or nutty flavor, coincided with the exhaustion of malic acid in
      the wine. The maximum concentration of diacetyl obtained during malolactic
      fermentation was strongly dependent on the oxygen concentration and the redox
      potential of the wine and, to a lesser extent, on the initial citric acid
      concentration. The final diacetyl concentration in the wine was also dependent on
      the concentration of SO2. Diacetyl combines rather strongly with SO2 (Kf = 7.2 x
      10(3) M(-1) in 0.1 M malate buffer [pH 3.5] at 30 degrees C). The reaction is
      exothermic and reversible. If the concentration of SO2 decreases during storage
      of the wine, the diacetyl concentration increases again.

PMID- 9925611
TI  - Isolation of a bacterial strain able to degrade branched nonylphenol.
AB  - Conventional enrichment of microorganisms on branched nonylphenol (NP) as only
      carbon and energy source yielded mixed cultures able to grow on the organic
      compound. However, plating yielded no single colonies capable, alone or in
      combination with other isolates, of degrading the NP in liquid culture.
      Therefore, a special approach was used, referred to as "serial dilution-plate
      resuspension," to reduce culture complexity. In this way, one isolate, TTNP3,
      tentatively identified as a Sphingomonas sp., was found to be able to grow on NP
      in liquid culture. Remarkably, this isolate was able to be filtered through a
      0.45-micrometer-pore-diameter filter. Moreover, isolate TTNP3 did not form
      visible colonies on mineral medium with NP, and it formed visible colonies on R2A
      agar only after a prolonged incubation of 1 week. High-performance liquid
      chromatography and gas chromatography-mass spectroscopy analysis of the culture
      media indicated that the strain starts the degradation of NP with a fission of
      the phenol ring and preferably uses the para isomer of NP and not the ortho
      isomer. No distinct accumulation of an intermediary product could be observed.

PMID- 9925612
TI  - Use of the integration elements encoded by the temperate lactococcal
      bacteriophage TP901-1 to obtain chromosomal single-copy transcriptional fusions
      in Lactococcus lactis.
AB  - Previously we showed that only one phage-expressed protein (Orf1), a 425-bp
      region upstream of the orf1 gene (presumably encoding a promoter), and the attP
      region are necessary and also sufficient for integration of the bacteriophage
      TP901-1 genome into the chromosome of Lactococcus lactis subsp. cremoris (B.
      Christiansen, L. Brondsted, F. K. Vogensen, and K. Hammer, J. Bacteriol. 178:5164
      5173, 1996). In this work, a further analysis of the phage-encoded elements
      involved in integration was performed. Here we demonstrate that even when the
      orf1 gene is separated from the attP region, the Orf1 protein is able to promote
      site-specific integration of an attP-carrying plasmid into the attB site on the
      L. lactis subsp. cremoris chromosome. Furthermore, the first detailed deletion
      analysis of an attP region of a phage infecting lactic acid bacteria was carried
      out. We show that a fragment containing 56 bp of the attP region, including the
      core, is sufficient for the site-specific integration of a nonreplicating plasmid
      into the chromosome of L. lactis subsp. cremoris when the orf1 gene is donated in
      trans. The functional 56-bp attP region of TP901-1 is substantially smaller than
      minimal attP regions identified for other phages. Based on the deletion analysis,
      several repeats located within the attP region seem to be necessary for site
      specific integration of the temperate bacteriophage TP901-1. By use of the
      integrative elements (attP and orf1) expressed by the temperate lactococcal
      bacteriophage TP901-1, a system for obtaining stable chromosomal single-copy
      transcriptional fusions in L. lactis was constructed. Two promoter-reporter
      integration vectors containing the reporter gene gusA or lacLM, encoding beta
      glucuronidase or beta-galactosidase, respectively, were constructed. Immediately
      upstream of both genes are found translational stop codons in all three reading
      frames as well as multiple restriction enzyme sites suitable for cloning of the
      promoter of interest. By transformation of L. lactis subsp. cremoris MG1363
      containing the integrase gene on a replicating plasmid, the promoter-reporter
      integration vectors integrated with a high frequency site specifically into the
      chromosomal attachment site attB used by bacteriophage TP901-1.

PMID- 9925613
TI  - Alterations in adhesion, transport, and membrane characteristics in an adhesion
      deficient pseudomonad.
AB  - A stable adhesion-deficient mutant of Burkholderia cepacia G4, a soil
      pseudomonad, was selected in a sand column assay. This mutant (ENV435) was
      compared to the wild-type strain by examining the adhesion of the organisms to
      silica sand and their transport through two aquifer sediments that differed in
      their sand, silt, and clay contents. We compared the longitudinal transport of
      the wild type and the adhesion mutant to the transport of a conservative chloride
      tracer in 25-cm-long glass columns. The transport of the wild-type strain was
      severely retarded compared to the transport of the conservative tracer in a
      variety of aquifer sediments, while the adhesion mutant and the conservative
      tracer traveled at similar rates. An intact sediment core study produced similar
      results; ENV435 was transported at a faster rate and in much greater numbers than
      G4. The results of hydrophobic interaction chromatography revealed that G4 was
      significantly more hydrophobic than ENV435, and polyacrylamide gel
      electrophoresis revealed significant differences in the lipopolysaccharide O
      antigens of the adhesion mutant and the wild type. Differences in this cell
      surface polymer may explain the decreased adhesion of strain ENV435.

PMID- 9925614
TI  - Evaluation of toxic effects of aeration and trichloroethylene oxidation on
      methanotrophic bacteria grown with different nitrogen sources.
AB  - In this study we evaluated specific and nonspecific toxic effects of aeration and
      trichloroethylene (TCE) oxidation on methanotrophic bacteria grown with different
      nitrogen sources (nitrate, ammonia, and molecular nitrogen). The specific toxic
      effects, exerted directly on soluble methane monooxygenase (sMMO), were evaluated
      by comparing changes in methane uptake rates and naphthalene oxidation rates
      following aeration and/or TCE oxidation. Nonspecific toxic effects, defined as
      general cellular damage, were examined by using a combination of epifluorescent
      cellular stains to measure viable cell numbers based on respiratory activity and
      measuring formate oxidation activities following aeration and TCE transformation.
      Our results suggest that aeration damages predominantly sMMO rather than other
      general cellular components, whereas TCE oxidation exerts a broad range of toxic
      effects that damage both specific and nonspecific cellular functions. TCE
      oxidation caused sMMO-catalyzed activity and respiratory activity to decrease
      linearly with the amount of substrate degraded. Severe TCE oxidation toxicity
      resulted in total cessation of the methane, naphthalene, and formate oxidation
      activities and a 95% decrease in the respiratory activity of methanotrophs. The
      failure of cells to recover even after 7 days of incubation with methane suggests
      that cellular recovery following severe TCE product toxicity is not always
      possible. Our evidence suggests that generation of greater amounts of sMMO per
      cell due to nitrogen fixation may be responsible for enhanced TCE oxidation
      activities of nitrogen-fixing methanotrophs rather than enzymatic protection
      mechanisms associated with the nitrogenase enzymes.

PMID- 9925615
TI  - Lethal effect of Rickettsia rickettsii on its tick vector (Dermacentor
      andersoni).
AB  - Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, was
      lethal for the majority of experimentally and transovarially infected Rocky
      Mountain wood ticks (Dermacentor andersoni). Overall, 94.1% of nymphs infected as
      larvae by feeding on rickettsemic guinea pigs died during the molt into adults
      and 88. 3% of adult female ticks infected as nymphs died prior to feeding. In
      contrast, only 2.8% of uninfected larvae failed to develop into adults over two
      generations. Infected female ticks incubated at 4 degreesC had a lower mortality
      (80.9%) than did those held at 21 degreesC (96.8%). Rickettsiae were vertically
      transmitted to 39.0% of offspring, and significantly fewer larvae developed from
      infected ticks. The lethal effect of R. rickettsii may explain the low prevalence
      of infected ticks in nature and affect its enzootic maintenance.

PMID- 9925616
TI  - Phylogenetic differences between particle-associated and planktonic ammonia
      oxidizing bacteria of the beta subdivision of the class Proteobacteria in the
      Northwestern Mediterranean Sea.
AB  - The aim of this study was to determine if there were differences between the
      types of ammonia-oxidizing bacteria of the beta subdivision of the class
      Proteobacteria associated with particulate material and planktonic samples
      obtained from the northwestern Mediterranean Sea. A nested PCR procedure
      performed with ammonia oxidizer-selective primers was used to amplify 16S rRNA
      genes from extracted DNA. The results of partial and full-length sequence
      analyses of 16S rRNA genes suggested that different groups of ammonia-oxidizing
      bacteria were associated with the two sample types. The particle-associated
      sequences were predominantly related to Nitrosomonas eutropha, while the
      sequences obtained from the planktonic samples were related to a novel marine
      Nitrosospira group (cluster 1) for which there is no cultured representative yet.
      A number of oligonucleotide probes specific for different groups of ammonia
      oxidizers were used to estimate the relative abundance of sequence types in
      samples of clone libraries. The planktonic libraries contained lower proportions
      of ammonia oxidizer clones (0 to 26%) than the particulate material libraries (9
      to 83%). Samples of the planktonic and particle-associated libraries showed that
      there were depth-related differences in the ammonia oxidizer populations, with
      the highest number of positive clones in the particle-associated sample occurring
      at a depth of 700 m. The greatest difference between planktonic and particle
      associated populations occurred at a depth of 400 m, where only 4% of the clones
      in the planktonic library were identified as Nitrosomonas clones, while 96% of
      these clones were identified as clones that were related to the marine
      Nitrosospira species. Conversely, all ammonia oxidizer-positive clones obtained
      from the particle-associated library were members of the Nitrosomonas group. This
      is the first indication that Nitrosomonas species and Nitrosospira species may
      occupy at least two distinct environmental niches in marine environments. The
      occurrence of these groups in different niches may result from differences in
      physiological properties and, coupled with the different environmental conditions
      associated with these niches, may lead to significant differences in the nature
      and rates of nitrogen cycling in these environments.

PMID- 9925617
TI  - High-level formation of active Pseudomonas cepacia lipase after heterologous
      expression of the encoding gene and its modified chaperone in Escherichia coli
      and rapid in vitro refolding.
AB  - The lipase from Pseudomonas cepacia ATCC 21808 (recently reclassified as
      Burkholderia cepacia) is widely used by organic chemists for enantioselective
      synthesis and is manufactured from recombinant P. cepacia harboring on a plasmid
      the clustered genes for lipase and its chaperone. High levels of expression of
      inactive lipase (40%) in Escherichia coli were achieved with pCYTEXP1 under the
      control of the strong, temperature-inducible lambdaPRL promoter. However, no
      overexpression of the lipase chaperone was achieved in E. coli. Thus, chemical
      refolding of inactive lipase in the absence of its chaperone yielded only 25
      U/mg, compared to 3,470 U of the purified lipase secreted by recombinant P.
      cepacia per mg. Sequence analysis of the chaperone revealed a high GC content
      (>90%) in the 5' region of the gene and the presence of a putative membrane
      anchor at the N terminus. Hence, the 5' region of the gene was replaced by a
      synthetic fragment, and the putative membrane anchor was removed by deletion of
      the first 34 or 70 N-terminal amino acids. Only truncation of the gene led to
      overexpression of the chaperone (up to 60%) in E. coli. With this chaperone, it
      was possible to obtain for the first time in a simple refolding procedure a
      highly active Pseudomonas lipase (classes I and II) expressed in E. coli with a
      specific activity of up to 4,850 U/mg and a yield of 314,000 U/g of E. coli wet
      cells.

PMID- 9925618
TI  - Changes in bacterial and eukaryotic community structure after mass lysis of
      filamentous cyanobacteria associated with viruses.
AB  - During an experiment in two laboratory-scale enclosures filled with lake water
      (130 liters each) we noticed the almost-complete lysis of the cyanobacterial
      population. Based on electron microscopic observations of viral particles inside
      cyanobacterial filaments and counts of virus-like particles, we concluded that a
      viral lysis of the filamentous cyanobacteria had taken place. Denaturing gradient
      gel electrophoresis (DGGE) of 16S ribosomal DNA fragments qualitatively monitored
      the removal of the cyanobacterial species from the community and the appearance
      of newly emerging bacterial species. The majority of these bacteria were related
      to the Cytophagales and actinomycetes, bacterial divisions known to contain
      species capable of degrading complex organic molecules. A few days after the
      cyanobacteria started to lyse, a rotifer species became dominant in the DGGE
      profile of the eukaryotic community. Since rotifers play an important role in the
      carbon transfer between the microbial loop and higher trophic levels, these
      observations confirm the role of viruses in channeling carbon through food webs.
      Multidimensional scaling analysis of the DGGE profiles showed large changes in
      the structures of both the bacterial and eukaryotic communities at the time of
      lysis. These changes were remarkably similar in the two enclosures, indicating
      that such community structure changes are not random but occur according to a
      fixed pattern. Our findings strongly support the idea that viruses can structure
      microbial communities.

PMID- 9925619
TI  - Characterization of two novel propachlor degradation pathways in two species of
      soil bacteria.
AB  - Propachlor (2-chloro-N-isopropylacetanilide) is an acetamide herbicide used in
      preemergence. In this study, we isolated and characterized a soil bacterium,
      Acinetobacter strain BEM2, that was able to utilize this herbicide as the sole
      and limiting carbon source. Identification of the intermediates of propachlor
      degradation by this strain and characterization of new metabolites in the
      degradation of propachlor by a previously reported strain of Pseudomonas (PEM1)
      support two different propachlor degradation pathways. Washed-cell suspensions of
      strain PEM1 with propachlor accumulated N-isopropylacetanilide, acetanilide,
      acetamide, and catechol. Pseudomonas strain PEM1 grew on propachlor with a
      generation time of 3.4 h and a Ks of 0.17 +/- 0.04 mM. Acinetobacter strain BEM2
      grew on propachlor with a generation time of 3.1 h and a Ks of 0.3 +/- 0.07 mM.
      Incubations with strain BEM2 resulted in accumulation of N-isopropylacetanilide,
      N-isopropylaniline, isopropylamine, and catechol. Both degradative pathways were
      inducible, and the principal product of the carbon atoms in the propachlor ring
      was carbon dioxide. These results and biodegradation experiments with the
      identified metabolites indicate that metabolism of propachlor by Pseudomonas sp.
      strain PEM1 proceeds through a different pathway from metabolism by Acinetobacter
      sp. strain BEM2.

PMID- 9925620
TI  - A novel chromogenic ester agar medium for detection of Salmonellae.
AB  - A novel agar medium, chromogenic Salmonella esterase (CSE) agar, for the
      differentiation of salmonellae is described. The agar contains peptones and
      nutrient extracts together with the following (grams per liter unless otherwise
      specified): 4-[2-(4-octanoyloxy-3, 5-dimethoxyphenyl)-vinyl]-quinolinium-1
      (propan-3-yl carboxylic acid) bromide (SLPA-octanoate; bromide form), 0.3223;
      lactose, 14. 65; trisodium citrate dihydrate, 0.5; Tween 20, 3.0; ethyl 4
      dimethylaminobenzoate, 0.035% (wt/vol), novobiocin, 70 mg liter-1. The key
      component of the medium is SLPA-octanoate, a newly synthesized ester formed from
      a C8 fatty acid and a phenolic chromophore. In CSE agar, the ester is hydrolyzed
      by Salmonella spp. to yield a brightly colored phenol which remains tightly bound
      within colonies. After 24 h of incubation at 37 or 42 degreesC, colonies of
      typical Salmonella spp. were burgundy colored on a transparent yellow background,
      whereas non-Salmonella spp. were white, cream, yellow or transparent. CSE agar
      was evaluated by using a panel of strains including a high proportion of
      Salmonella and non-Salmonella strains giving atypical reactions on other
      differential agars. The sensitivity (93.1%) of CSE agar for non-typhi salmonellae
      compared favorably with those of Rambach (82. 8%), xylose-lysine-deoxycholate
      (XLD; 91.4%), Hektoen-enteric (89.7%), and SM ID (91.4%) agars. The specificity
      (93.9%) was also comparable to those of other Salmonella media (SM ID agar,
      95.9%; Rambach agar, 91.8%; XLD agar, 91.8%; Hektoen-enteric agar, 87.8%).
      Strains of Citrobacter freundii and Proteus spp. giving false-positive reactions
      with other media gave a negative color reaction on CSE agar. CSE agar enabled the
      detection of >30 Salmonella serotypes, including agona, anatum, enteritidis,
      hadar, heidelberg, infantis, montevideo, thompson, typhimurium, and virchow,
      which accounted for 91.8% of the salmonella isolates recorded by the Public
      Health Laboratory Service (Colindale, London, England) for 1997.

PMID- 9925621
TI  - Simultaneous monitoring of cell number and metabolic activity of specific
      bacterial populations with a dual gfp-luxAB marker system.
AB  - A dual marker system was developed for simultaneous quantification of bacterial
      cell numbers and their activity with the luxAB and gfp genes, encoding bacterial
      luciferase and green fluorescent protein (GFP), respectively. The bioluminescence
      phenotype of the luxAB biomarker is dependent on cellular energy status. Since
      cellular metabolism requires energy, bioluminescence output is directly related
      to the metabolic activity of the cells. By contrast, GFP fluorescence has no
      energy requirement. Therefore, by combining these two biomarkers, total cell
      number and metabolic activity of a specific marked cell population could be
      monitored simultaneously. Two different bacterial strains, Escherichia coli
      DH5alpha and Pseudomonas fluorescens SBW25, were chromosomally tagged with the
      dual marker cassette, and the cells were monitored under different conditions by
      flow cytometry, plate counting, and luminometry. During log-phase growth, the
      luciferase activity was proportional to the number of GFP-fluorescent cells and
      culturable cells. Upon entrance into stationary phase or during starvation,
      luciferase activity decreased due to a decrease in cellular metabolic activity of
      the population, but the number of GFP-fluorescing cells and culturable cells
      remained relatively stable. In addition, we optimized a procedure for extraction
      of bacterial cells from soil, allowing GFP-tagged bacteria in soil samples to be
      quantitated by flow cytometry. After 30 days of incubation of P. fluorescens
      SBW25::gfp/lux in soil, the cells were still maintained at high population
      densities, as determined by GFP fluorescence, but there was a slow decline in
      luciferase activity, implicating nutrient limitation. In conclusion, the dual
      marker system allowed simultaneous monitoring of the metabolic activity and cell
      number of a specific bacterial population and is a promising tool for monitoring
      of specific bacteria in situ in environmental samples.

PMID- 9925622
TI  - Poly-3-hydroxybutyrate in Legionella pneumophila, an energy source for survival
      in low-nutrient environments.
AB  - Chloroform-soluble material was extracted from two strains of L. pneumophila
      serogroup 1 following growth in continuous culture. The purified material was
      identified as poly-3-hydroxybutyrate (PHB) by nuclear magnetic resonance
      spectroscopy and by gas chromatography-mass spectrometry. PHB yields of up to 16%
      of cell dry weight were extracted from culture samples. The PHB was located in
      electron-dense intracellular inclusions, which fluoresced bright yellow when
      stained with the lipophilic dye Nile red. A Nile red spectrofluorometric assay
      provided a more accurate and reliable determination of the PHB content. PHB
      accumulation increased threefold during iron-limited culture and was inversely
      related to the concentration of iron metabolized. Chemostat-grown cells survived
      in a culturable state for at least 600 days when incubated at 24 degreesC in a
      low-nutrient tap water environment. Nile red spectrofluorometry and flow
      cytometry demonstrated that PHB reserves were utilized during starvation. PHB
      utilization, as revealed by the decline in mean cellular fluorescence and cell
      complexity, correlated with loss of culturability. Fluorescence microscopy
      provided visual evidence of PHB utilization, with a marked reduction in the
      number of Nile red-stained granules during starvation. Heat shock treatment
      failed to resuscitate nonculturable cells. This study demonstrates that L.
      pneumophila accumulates significant intracellular reserves of PHB, which promote
      its long-term survival under conditions of starvation.

PMID- 9925623
TI  - Regulatory factors associated with synthesis of the osmolyte glycine betaine in
      the halophilic methanoarchaeon Methanohalophilus portucalensis.
AB  - The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize de
      novo and accumulate beta-glutamine, Nepsilon-acetyl-beta-lysine, and glycine
      betaine (betaine) as compatible solutes (osmolytes) when grown at elevated salt
      concentrations. Both in vivo and in vitro betaine formation assays in this study
      confirmed previous nuclear magnetic resonance 13C-labelling studies showing that
      the de novo synthesis of betaine proceeded from glycine, sarcosine, and
      dimethylglycine to form betaine through threefold methylation. Exogenous
      sarcosine (1 mM) effectively suppressed the intracellular accumulation of
      betaine, and a higher level of sarcosine accumulation was accompanied by a lower
      level of betaine synthesis. Exogenous dimethylglycine has an effect similar to
      that of betaine addition, which increased the intracellular pool of betaine and
      suppressed the levels of Nepsilon-acetyl-beta-lysine and beta-glutamine. Both in
      vivo and in vitro betaine formation assays with glycine as the substrate showed
      only sarcosine and betaine, but no dimethylglycine. Dimethylglycine was detected
      only when it was added as a substrate in in vitro assays. A high level of
      potassium (400 mM and above) was necessary for betaine formation in vitro.
      Interestingly, no methylamines were detected without the addition of KCl. Also,
      high levels of NaCl and LiCl (800 mM) favored sarcosine accumulation, while a
      lower level (400 mM) favored betaine synthesis. The above observations indicate
      that a high sarcosine level suppressed multiple methylation while dimethylglycine
      was rapidly converted to betaine. Also, high levels of potassium led to greater
      amounts of betaine, while lower levels of potassium led to greater amounts of
      sarcosine. This finding suggests that the intracellular levels of both sarcosine
      and potassium are associated with the regulation of betaine synthesis in M.
      portucalensis.

PMID- 9925624
TI  - Green fluorescent protein as a reporter to monitor gene expression and food
      colonization by Aspergillus flavus.
AB  - Transformants of Aspergillus flavus containing the Aequorea victoria gfp gene
      fused to a viral promoter or the promoter region and 483 bp of the coding region
      of A. flavus aflR expressed green fluorescence detectable without a microscope or
      filters. Expression of green fluorescent protein fluorescence was correlated with
      resistance to aflatoxin accumulation in five corn genotypes inoculated with these
      transformants.

PMID- 9925625
TI  - Phylogenetic diversity of symbiotic methanogens living in the hindgut of the
      lower termite Reticulitermes speratus analyzed by PCR and in situ hybridization.
AB  - A phylogenetic analysis of the sequences of 60 clones of archaeal small-subunit
      rRNA genes amplified from the termite Reticulitermes speratus revealed that most
      of them (56 clones) clustered in the genus Methanobrevibacter. Three clones were
      classified in the order Thermoplasmales. The Methanobrevibacter-related symbionts
      were detected by in situ hybridization analysis.

PMID- 9925626
TI  - Evaluation of immunomagnetic separation for recovery of infectious
      Cryptosporidium parvum oocysts from environmental samples.
AB  - Two commercial immunomagnetic separation (IMS) kits for Cryptosporidium were
      compared for recovery of oocysts from environmental samples. Oocyst recovery
      efficiencies with the Dynal and Crypto-Scan kits ranged from 62 to 100% and 34 to
      74%, respectively, for seeded environmental water concentrates (turbidity of 210
      to 11,480 nephelometric turbidity units). Recovery efficiencies were dependent on
      the mechanism of agitation during the magnetic capture procedure. An assay
      combining in vitro cell culture and reverse transcriptase PCR demonstrated that
      oocysts recovered by IMS retained their infectivity.

PMID- 9925627
TI  - Isolation of Deinococcus species from commercial oyster extract.
AB  - Deinococci with radiation resistance greater than that of Deinococcus radiophilus
      (ATCC 27603) were isolated from three commercial oyster extracts stored at 4, 20,
      and 30 degreesC. During storage the number of other bacteria declined and
      deinococci became the predominant group in the microflora, particularly at 20
      degreesC, although at 30 degreesC the number of deinococci as well rapidly
      declined. The results suggest that the natural habitat of deinococci is an
      aerobic environment containing a slightly elevated saline content, soluble
      protein, and low sugar levels.

PMID- 9925628
TI  - New assay for rhizobitoxine based on inhibition of 1-aminocyclopropane-1
      carboxylate synthase.
AB  - Rhizobitoxine is synthesized by the legume symbiont Bradyrhizobium elkanii and
      the plant pathogen Burkholderia andropogonis. Rhizobitoxine competitively
      inhibited 1-aminocyclopropane-1-carboxylate (ACC) synthase bLE-ACS2 from the
      tomato, a key enzyme in the pathway of ethylene biosynthesis. Based on this
      inhibition of ACC synthase, we have developed a new assay for rhizobitoxine.

PMID- 9925629
TI  - Effect of aromatic compounds on cellular fatty acid composition of Rhodococcus
      opacus.
AB  - In cells of Rhodococcus opacus GM-14, GM-29, and 1CP, the contents of branched
      (10-methyl) fatty acids increased from 3% to 15 to 34% of the total fatty acids
      when the cells were grown on benzene, phenol, 4-chlorophenol, chlorobenzene, or
      toluene as the sole source of carbon and energy, in comparison with cells grown
      on fructose. In addition, the content of trans-hexadecenoic acid increased from
      5% to 8 to 18% with phenol or chlorophenol as the carbon source. The 10-methyl
      branched fatty acid content of R. opacus GM-14 cells increased in a dose-related
      manner following exposure to phenol or toluene when toluene was not utilized as
      the growth substrate. The results suggest that 10-methyl branched fatty acids may
      participate in the adaptation of R. opacus to lipophilic aromatic compounds.

PMID- 9925630
TI  - Comparative study of biological properties and electrophoretic characteristics of
      lipopolysaccharide from eel-virulent and eel-A virulent Vibrio vulnificus
      strains.
AB  - In Vibrio vulnificus, virulence for eels is associated with serovar E strains. In
      this study, we investigated some biological properties of purified
      lipopolysaccharides (LPSs) from serovar E and non-serovar E strains. Purified
      LPSs retained their O-polysaccharidic side chains and did not show any
      differences that could be related to host specificity, except for serological
      differences.

PMID- 9925632
TI  - Exopolysaccharide-producing bacteria from sugar beets.
AB  - Six hundred microorganisms were isolated from sugar beets collected from
      different parts of Finland to study their slime production. A total of 170 of
      them produced exopolysaccharides, of which 35% were heteropolysaccharides. The
      yield of heteropolysaccharides from sucrose was lower than that of dextrans. Five
      isolates, which were chosen for closer study, were identified as Leuconostoc
      mesenteroides (two species), Rahnella aquatilis (two species), and Enterobacter
      amnigenus.

PMID- 9925631
TI  - Enhancement of solar water pasteurization with reflectors.
AB  - A simple and reliable method that could be used in developing countries to
      pasteurize milk and water with solar energy is described. A cardboard reflector
      directs sunshine onto a black jar, heating water to pasteurizing temperatures in
      several hours. A reusable water pasteurization indicator verifies that
      pasteurization temperatures have been reached.

PMID- 9925633
TI  - Isolation of fecal coliform bacteria from the diamondback terrapin (Malaclemys
      terrapin centrata).
AB  - Total and fecal coliform bacteria were isolated from the cloaca and feces of the
      estuarine diamondback terrapin. The majority of samples contained fecal
      coliforms. Escherichia coli was the predominant fecal coliform species isolated,
      and members of the genus Salmonella were isolated from 2 of 39 terrapins. Fecal
      coliform numbers are used to regulate shellfish harvests, and diamondback
      terrapins inhabit the brackish-water habitats where oyster beds are found;
      therefore, these findings have implications for the efficacy of current
      regulatory parameters in shellfishing waters.

PMID- 9925634
TI  - Detection of shiga-like toxin (stx1 and stx2), intimin (eaeA), and
      enterohemorrhagic Escherichia coli (EHEC) hemolysin (EHEC hlyA) genes in animal
      feces by multiplex PCR.
AB  - A multiplex PCR was developed for the rapid detection of genes encoding Shiga
      toxins 1 and 2 (stx1 and stx2), intimin (eaeA), and enterohemolysin A (hlyA) in
      444 fecal samples derived from healthy and clinically affected cattle, sheep,
      pigs, and goats. The method involved non-solvent-based extraction of nucleic acid
      from an aliquot of an overnight culture of feces in EC (modified) broth. The
      detection limit of the assay for both fecal samples and pure cultures was between
      18 and 37 genome equivalents. stx1 and hlyA were the most commonly encountered
      virulence factors.

PMID- 9925635
TI  - A comparative study of methods to validate formaldehyde decontamination of
      biological safety cabinets.
AB  - Methods of validation of formaldehyde decontamination of biological safety
      cabinets were compared. Decontamination of metal strips inoculated with
      Mycobacterium bovis, poliovirus, or Bacillus spp. spores was compared with the
      results obtained with three biological indicators. Conditions for successful
      decontamination, particularly relative humidity, were defined. The Attest 1291
      biological indicator was the only biological indicator which was an aid in the
      detection of gross decontamination failure.

PMID- 9925636
TI  - RNAi and double-strand RNA.

PMID- 9925637
TI  - "Cre"-ating mouse mutants-a meeting review on conditional mouse genetics.

PMID- 9925638
TI  - Telomeric chromatin modulates replication timing near chromosome ends.
AB  - Saccharomyces cerevisiae telomeric DNA replicates late in S phase, and telomeric
      genes are transcriptionally silent. Transcriptional repression of telomere
      proximal genes results from silent chromatin initiating at the chromosome end,
      but the relationship between telomeric chromatin and DNA replication is unknown.
      Mutations in SIR3, a silent chromatin component, cause telomeric DNA on
      chromosome V to replicate much earlier because of earlier initiation of a nearby
      replication origin, the Y' ARS. A second telomere-proximal ARS, from an X
      element, does not act as an origin in a wild-type strain, whereas in a sir3 cell
      it does. We conclude that telomeric chromatin has a Sir3-dependent inhibitory
      effect on DNA replication.

PMID- 9925639
TI  - A role for ATR in the DNA damage-induced phosphorylation of p53.
AB  - Phosphorylation at Ser-15 may be a critical event in the up-regulation and
      functional activation of p53 during cellular stress. In this report we provide
      evidence that the ATM-Rad3-related protein ATR regulates phosphorylation of Ser
      15 in DNA-damaged cells. Overexpression of catalytically inactive ATR (ATRki) in
      human fibroblasts inhibited Ser-15 phosphorylation in response to gamma
      irradiation and UV light. In gamma-irradiated cells, ATRki expression selectively
      interfered with late-phase Ser-15 phosphorylation, whereas ATRki blocked UV
      induced Ser-15 phosphorylation in a time-independent manner. ATR phosphorylated
      p53 at Ser-15 and Ser-37 in vitro, suggesting that p53 is a target for
      phosphorylation by ATR in DNA-damaged cells.

PMID- 9925640
TI  - Vein expression is induced by the EGF receptor pathway to provide a positive
      feedback loop in patterning the Drosophila embryonic ventral ectoderm.
AB  - The presence of a single EGF receptor in Drosophila is contrasted by multiple
      ligands activating it. This work explores the role of two ligands, Spitz and
      Vein, in the embryonic ventral ectoderm. Spitz is a potent ligand, whereas Vein
      is an intrinsically weak activating ligand. We show that secreted Spitz emanating
      from the midline, triggers expression of vein in the ventral-most cell rows, by
      inducing expression of the ETS domain transcription factor Pointed P1. In the
      absence of Vein, lateral cell fates are not induced when Spitz levels are
      compromised. The positive feedback loop of Vein generates a robust mechanism for
      patterning the ventral ectoderm.

PMID- 9925641
TI  - Multiple docking sites on substrate proteins form a modular system that mediates
      recognition by ERK MAP kinase.
AB  - MAP kinases phosphorylate specific groups of substrate proteins. Here we show
      that the amino acid sequence FXFP is an evolutionarily conserved docking site
      that mediates ERK MAP kinase binding to substrates in multiple protein families.
      FXFP and the D box, a different docking site, form a modular recognition system,
      as they can function independently or in combination. FXFP is specific for ERK,
      whereas the D box mediates binding to ERK and JNK MAP kinase, suggesting that the
      partially overlapping substrate specificities of ERK and JNK result from
      recognition of shared and unique docking sites. These findings enabled us to
      predict new ERK substrates and design peptide inhibitors of ERK that functioned
      in vitro and in vivo.

PMID- 9925642
TI  - Nim1-related kinases coordinate cell cycle progression with the organization of
      the peripheral cytoskeleton in yeast.
AB  - The mechanisms that couple cell cycle progression with the organization of the
      peripheral cytoskeleton are poorly understood. In Saccharomyces cerevisiae, the
      Swe1 protein has been shown previously to phosphorylate and inactivate the cyclin
      dependent kinase, Cdc28, thereby delaying the onset of mitosis. The nim1-related
      protein kinase, Hsl1, induces entry into mitosis by negatively regulating Swe1.
      We have found that Hsl1 physically associates with the septin cytoskeleton in
      vivo and that Hsl1 kinase activity depends on proper septin function. Genetic
      analysis indicates that two additional Hsl1-related kinases, Kcc4 and Gin4, act
      redundantly with Hsl1 to regulate Swe1. Kcc4, like Hsl1 and Gin4, was found to
      localize to the bud neck in a septin-dependent fashion. Interestingly, hsl1 kcc4
      gin4 triple mutants develop a cellular morphology extremely similar to that of
      septin mutants. Consistent with the idea that Hsl1, Kcc4, and Gin4 link entry
      into mitosis to proper septin organization, we find that septin mutants incubated
      at the restrictive temperature trigger a Swe1-dependent mitotic delay that is
      necessary to maintain cell viability. These results reveal for the first time how
      cells monitor the organization of their cytoskeleton and demonstrate the
      existence of a cell cycle checkpoint that responds to defects in the peripheral
      cytoskeleton. Moreover, Hsl1, Kcc4, and Gin4 have homologs in higher eukaryotes,
      suggesting that the regulation of Swe1/Wee1 by this class of kinases is highly
      conserved.

PMID- 9925643
TI  - ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA
      deadenylation/degradation system.
AB  - We have developed an in vitro mRNA stability system using HeLa cell cytoplasmic
      S100 extracts and exogenous polyadenylated RNA substrates that reproduces
      regulated aspects of mRNA decay. The addition of cold poly(A) competitor RNA
      activated both a sequence-specific deadenylase activity in the extracts as well
      as a potent, ATP-dependent ribonucleolytic activity. The rates of both
      deadenylation and degradation were up-regulated by the presence of a variety of
      AU-rich elements in the body of substrate RNAs. Competition analyses demonstrated
      that trans-acting factors were required for RNA destabilization by AU-rich
      elements. The approximately 30-kD ELAV protein HuR specifically bound to RNAs
      containing an AU-rich element derived from the TNF-alpha mRNA in the in vitro
      system. Interaction of HuR with AU-rich elements, however, was not associated
      with RNA destabilization. Interestingly, recombinant ELAV proteins specifically
      stabilized deadenylated intermediates generated from the turnover of AU-rich
      element-containing substrate RNAs. These data suggest that mammalian ELAV
      proteins play a role in regulating mRNA stability by influencing the access of
      degradative enzymes to RNA substrates.

PMID- 9925644
TI  - Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1.
AB  - In the early Caenorhabditis elegans embryo, maternally expressed PIE-1 protein is
      required in germ-line blastomeres to inhibit somatic differentiation, maintain an
      absence of mRNA transcription, and block phosphorylation of the RNA polymerase II
      large subunit (Pol II) carboxy-terminal domain (CTD). We have determined that PIE
      1 can function as a transcriptional repressor in cell culture assays. By fusing
      PIE-1 sequences to the yeast GAL4 DNA-binding domain, we have identified a PIE-1
      repression domain that appears to inhibit the transcriptional machinery directly.
      A sequence element that is required for this repressor activity is similar to the
      Pol II CTD heptapeptide repeat, suggesting that the PIE-1 repression domain might
      target a protein complex that can bind the CTD. An alteration of this sequence
      element that blocks repression also impairs the ability of a transgene to rescue
      a pie-1 mutation, suggesting that this repressor activity may be important for
      PIE-1 function in vivo.

PMID- 9925645
TI  - p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step.
AB  - Cell-cycle arrest is thought to be required for differentiation of muscle cells.
      However, the molecules controlling cell-cycle exit and the differentiation
      step(s) dependent on cell-cycle arrest are poorly understood. Here we show that
      two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation
      of skeletal muscle and alveoli in the lungs. Mice lacking both p21 and p57 fail
      to form myotubes, display increased proliferation and apoptotic rates of
      myoblasts, and display endoreplication in residual myotubes. This point of arrest
      during muscle development is identical to that of mice lacking the myogenic
      transcription factor myogenin, indicating a role for cell-cycle exit in myogenin
      function. Expression of myogenin, p21, and p57 is parallel but independent, and
      in response to differentiation signals, these proteins are coordinately regulated
      to trigger both cell-cycle exit and a dependent muscle-specific program of gene
      expression to initiate myoblast terminal differentiation and muscle formation.

PMID- 9925647
TI  - High density lipoprotein receptors, binding proteins, and ligands.
AB  - Several HDL binding proteins, quite disparate in structure, have recently been
      cloned and their role in HDL metabolism is currently being assessed. High density
      lipoprotein binding protein, HBP (vigilin), which lacks a transmembrane domain is
      responsive to cell cholesterol levels, but its physiological significance remains
      unknown. On the other hand much is known about SR-B1, a member of the class B
      scavenger receptors. The level of SR-B1 expression correlates with both the
      selective transfer of cholesteryl ester into cells and cholesterol efflux from
      cells, the transfers probably mediated after docking of HDL at the cell surface.
      SR-B1 exhibits broad ligand specificity and, in animal models, appears to be
      regulated by the action of pituitary hormones that stimulate steroidogenesis,
      suggesting an important role for steroid hormone production in supplying
      precursor cholesterol. Another candidate HDL receptor, HB2, one of a pair of
      liver HDL binding proteins, shows high sequence homology with adhesion molecules,
      particularly activated leukocyte-cell adhesion molecule (ALCAM). When HB2 is
      overexpressed in cells, HDL binding increases. After PMA-induced differentiation
      of monocytes into macrophages, HB2 mRNA is strikingly elevated, which correlates
      with increased binding of HDL, but is down-regulated by cholesterol loading of
      macrophages. The ligand specificity of the HDL receptors, confounded by
      nonspecific lipid interactions, remains controversial. Their affinity for apoA-I
      versus apoA-I/A-II-rich HDL particles has clinical implications; both specific
      sequences in apoA-I and amphipathic alpha-helices may determine binding events.
      Post-receptor-mediated signalling events may regulate cell functions which,
      although not primarily related to lipid transport, nevertheless protect against
      coronary artery disease. Growing evidence for the involvement of lipid-poor apoA
      I as a mediator of such pathways is also discussed.

PMID- 9925646
TI  - Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response
      to BMP signaling.
AB  - Previous work has indicated that signals from the floor plate and notochord
      promote chondrogenesis of the somitic mesoderm. These tissues, acting through the
      secreted signaling molecule Sonic hedgehog (Shh), appear to be critical for the
      formation of the sclerotome. Later steps in the differentiation of sclerotome
      into cartilage may be independent of the influence of these axial tissues.
      Although the signals involved in these later steps have not yet been pinpointed,
      there is substantial evidence that the analogous stages of limb bud
      chondrogenesis require bone morphogenetic protein (BMP) signaling. We show here
      that presomitic mesoderm (psm) cultured in the presence of Shh will differentiate
      into cartilage, and that the later stages of this differentiation process
      specifically depend on BMP signaling. We find that Shh not only acts in
      collaboration with BMPs to induce cartilage, but that it changes the competence
      of target cells to respond to BMPs. In the absence of Shh, BMP administration
      induces lateral plate gene expression in cultured psm. After exposure to Shh, BMP
      signaling no longer induces expression of lateral plate markers but now induces
      robust chondrogenesis in cultured psm. Shh signals are required only transiently
      for somitic chondrogenesis in vitro, and act to provide a window of competence
      during which time BMP signals can induce chondrogenic differentiation. Our
      findings suggest that chondrogenesis of somitic tissues can be divided into two
      separate phases: Shh-mediated generation of precursor cells, which are competent
      to initiate chondrogenesis in response to BMP signaling, and later exposure to
      BMPs, which act to trigger chondrogenic differentiation.

PMID- 9925648
TI  - Effects of estrogenic oral contraceptives on the lipoprotein B particle system
      defined by apolipoproteins E and C-III content.
AB  - Apolipoproteins E and C-III are modulators of lipoprotein metabolism that could
      affect development of atherosclerosis. The prevalence in plasma of apoB
      containing particles (LpB) that contain either apoE or apoC-III, both or neither,
      and the effect of estrogen on these lipoproteins are unknown. The LpB particle
      system, defined by the presence or absence of apoE or C-III, was studied in 13
      normolipidemic women, 7 nonusers and 6 users of oral contraceptives. Fasting
      plasma was separated by anti-apoE and C-III affinity chromatography and
      ultracentrifugation into four types of VLDL, IDL, and LDL particles: with apoE
      but not apoC-III (E+C-), apoC-III but not apoE (E-C+), both (E+C+) or neither (E
      C-). The predominant VLDL particles were E-C- (42% in nonusers, 56% in users) and
      E+C+ (39% in nonusers, 24% in users), suggesting that apoE and apoC-III mainly
      exist together in VLDL. In IDL, E-C- was the major fraction (74% nonusers, 81%
      users), and in LDL, it was 99% in both groups. The triglycerides in VLDL and IDL
      were mainly contained in C+ particles (79% and 66% of the total VLDL and IDL
      triglycerides, respectively). Within VLDL, IDL, and LDL, E-C- particles had the
      smallest size and E+C+ or E-C+ the largest. Users had higher concentrations of
      VLDL E-C- (280%) and IDL E-C- (90%) particles than nonusers. They also had higher
      free cholesterol and cholesteryl ester concentrations associated with these
      fractions and with VLDL E-C+. The triglyceride contents of VLDL E-C- particles
      were lower in users of oral contraceptives than in nonusers. This study
      demonstrates that the elevated VLDL TG concentrations in users of estrogen
      dominant oral contraceptives is mainly caused by an increased concentration of
      small VLDL particles that have reduced TG content, and that do not have apoE and
      C-III. These particles may have lower atherogenicity than particles enriched with
      apoE and C-III.-Khoo, C., H. Campos, H. Judge, and F. M. Sacks. Effects of
      estrogenic oral contraceptives on the lipoprotein B particle system defined by
      apolipoproteins E and C-III content.

PMID- 9925649
TI  - Phenotypic consequences of a deletion of exons 2 and 3 of the LDL receptor gene.
AB  - Screening for structural alterations of the low density lipoprotein (LDL)
      receptor gene by Southern blot analysis revealed an abnormal band pattern in one
      subject with a clinical diagnosis of homozygous familial hypercholesterolemia
      (FH). The molecular defect was further characterized by polymerase chain reaction
      and cDNA sequencing. These analyses identified a 4.8 kb in-frame deletion of
      exons 2 and 3, where exon 1 was spliced to exon 4. This deletion is expected to
      produce a receptor that has lost the two first cysteine-rich repeats of the
      ligand-binding domain. Previously published data of in vitro site-directed
      mutagenesis has shown that binding of LDL to such a receptor is reduced to 70% of
      normal. A mild phenotype in our FH homozygote is consistent with that
      observation. In contrast, heterozygotes carrying this deletion have a relatively
      more severe phenotype that is comparable to that of heterozygotes carrying a null
      allele. A severe phenotype was also found in a compound heterozygote carrying
      this deletion. Possible mechanisms for this phenotypic variability are discussed.
      Rodningen, O. K., S. Tonstad, J. D. Medh, D. A. Chappell, L. Ose, and T. P.
      Leren. Phenotypic consequences of a deletion of exons 2 and 3 of the LDL receptor
      gene.

PMID- 9925650
TI  - Molecular defects underlying Wolman disease appear to be more heterogeneous than
      those resulting in cholesteryl ester storage disease.
AB  - Human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) is essential for
      the intralysosomal metabolism of cholesteryl esters and triglycerides taken up by
      receptor-mediated endocytosis of lipoprotein particles. The key role of the
      enzyme in intracellular lipid homeostasis is illustrated by two lysosomal storage
      diseases inherited as autosomal recessive traits. Wolman disease, associated with
      deficient hLAL activity, leads to massive intracellular substrate accumulation
      and is always fatal in early infancy. Cholesteryl ester storage disease (CESD),
      in contrast, is characterized by very low levels of enzymic activity sufficient
      to allow survival of the affected patients into adulthood. In order to elucidate
      the underlying molecular defects in Wolman disease, we have characterized the
      hLAL gene in two female Wolman patients of German and Turkish origin by SSCP and
      DNA sequence analysis. Our results demonstrate that the German proband was
      compound heterozygous for an 8-bp deletion in exon 3 and a 2-bp deletion in exon
      4 of the hLAL gene. These frameshift mutations lead to protein truncation at
      amino acid positions 24 and 116 and to complete loss of hydrolytic activity. The
      Turkish proband, in contrast, was homozygous for a G(1064)-->T substitution in
      exon 10 of the hLAL gene which converts the completely conserved glycine (GGG)
      residue at position 321 of the mature enzyme to tryptophan (TGG). In vitro
      expression of the hLAL(Gly(321)-->Trp) cDNA construct revealed that the amino
      acid replacement results in a more than 99% reduction of neutral lipid
      hydrolysis. The mutations provide new insights into the molecular basis of Wolman
      disease which is apparently more heterogeneous at the genetic level than
      cholesteryl ester storage disease.-Lohse, P., S. Maas, P. Lohse, A. C. Sewell, O.
      P. van Diggelen, and D. Seidel. Molecular defects underlying Wolman disease
      appear to be more heterogeneous than those resulting in cholesteryl ester storage
      disease.

PMID- 9925651
TI  - Hepatic lipase activity influences high density lipoprotein subclass distribution
      in normotriglyceridemic men. Genetic and pharmacological evidence.
AB  - Several studies have reported an inverse relationship between hepatic lipase
      activity and plasma high density lipoprotein (HDL) cholesterol concentrations.
      The purpose of the present study was to determine whether genetic and
      pharmacological variation in hepatic lipase activity alters the distribution of
      HDL subclasses. Two independent analytical methods (nuclear magnetic resonance
      and gradient gel electrophoresis) were used to compare HDL subclass distributions
      in 11 homozygotes for the -514C allele of hepatic lipase and in 6 homozygotes for
      the -514T allele. Mean hepatic lipase activity was 45 +/- 15 mmol. l(-1). hr(-1)
      in -514C homozygotes and 20 +/- 7 mmol. l(-1). hr(-1) in -514T homozygotes. Both
      analytical methods indicated that HDL(2b) was significantly higher and HDL(3a)
      was significantly lower in -514T homozygotes than in -514C homozygotes. No
      differences were noted in the other HDL fractions (HDL(2a), HDL(3b), and
      HDL(3c)). To determine the effects of increased hepatic lipase activity, 20 men
      were given the synthetic anabolic steroid, stanozolol. Stanozolol treatment
      increased hepatic lipase activity more than two-fold (38 +/- 18 to 85 +/- 25
      mmol. l(-1). hr(-1) ), and markedly reduced the plasma concentrations of the
      larger HDL subclasses (HDL(2b) and HDL(2a)). The plasma concentrations of the
      smallest HDL subclasses (HDL(3b) and HDL(3c)) were unchanged by stanozolol
      treatment. Taken together, these genetic and pharmacological data indicate that
      variation in hepatic lipase activity has highly specific effects on the
      distribution of HDL subclasses in the circulation.-Grundy, S. M., G. L. Vega, J.
      D. Otvos, D. L. Rainwater, and J. C. Cohen. Hepatic lipase activity influences
      high density lipoprotein subclass distribution in normotriglyceridemic men:
      genetic and pharmacological evidence.

PMID- 9925652
TI  - In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques
      treated with female hormones.
AB  - Premenopausal women and postmenopausal women given estrogen are protected from
      cardiovascular diseases compared with men. Previous studies investigated whether
      estrogen treatment protects low density lipoprotein (LDL) from in vitro oxidation
      as a potential mechanistic explanation for the beneficial effect of estrogen.
      Results of these studies are mixed, and very few studies considered aspects of
      LDL that influence LDL oxidation. This study investigated whether treating
      postmenopausal female cynomolgus macaques with conjugated equine estrogens (CEE),
      medroxyprogesterone acetate (MPA), CEE + MPA, or tamoxifen, a mixed estrogen
      receptor agonist/antagonist, would protect LDL from in vitro oxidation. LDL was
      isolated from monkeys fed an atherogenic diet for 12 weeks or the same diet with
      CEE, MPA, CEE + MPA, or tamoxifen added at levels equivalent (on a caloric basis)
      to those given to women. LDL was subjected to Cu(2+) (3 micromol/L) or 2,2'
      azobis(2-amidinopropane) dihydrochloride (AAPH, 1 mmol/L) and LDL oxidation was
      determined by the lag time before rapid formation of conjugated dienes and by the
      maximal rate of conjugated diene formation (propagation rate). Lag times and
      propagation rates were not affected by treatment. Lag times for Cu(2+) oxidation
      were related to LDL tocopherol while lag times for AAPH oxidation were related to
      high density lipoprotein (HDL) cholesterol and to LDL molecular weight.
      Multivariate analysis showed that LDL alpha- and gamma-tocopherol together could
      explain 27% of the variation in Cu(2+) mediated lag time (P < 0.005) among
      animals while HDL cholesterol, LDL gamma-tocopherol, and LDL molecular weight
      combined could explain 40% of the variation in AAPH- mediated lag time (P =
      0.0006) among animals. After adjustment for these predictors, LDL lag times were
      not affected by treatment. In conclusion, in monkeys treated with female
      hormones, multiple factors influence in vitro low density lipoprotein (LDL)
      oxidation; future work will be needed to determine whether estrogen alters
      oxidation of LDL in the artery.-Schwenke, D. C., J. D. Wagner, and M. R. Adams.
      In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques
      treated with female hormones.

PMID- 9925653
TI  - Lipoproteins inhibit macrophage activation by lipoteichoic acid.
AB  - Regulation of lipid metabolism during infection is thought to be part of host
      defense, as lipoproteins neutralize endotoxin (LPS) and viruses. Gram-positive
      infections also induce disturbances in lipid metabolism. Therefore, we
      investigated whether lipoproteins could inhibit the toxic effects of lipoteichoic
      acid (LTA), a fragment of gram-positive bacteria. LTA activated RAW264.7
      macrophage cells, stimulating production of tumor necrosis factor (TNF) in a dose
      dependent matter, but produced less TNF than that seen after LPS activation. High
      density (HDL) or low density lipoprotein (LDL) alone inhibited the ability of LPS
      to stimulate TNF production, but had little effect on the activation by LTA. When
      a maximally effective dose of LTA was mixed with lipoproteins and 10% lipoprotein
      depleted plasma (LPDP), the ability of LTA to stimulate macrophage production of
      TNF was inhibited. HDL, LDL, and the synthetic particle, Soyacal, when mixed with
      LPDP, were able to inhibit the ability of LTA to activate macrophages.
      Lipopolysaccharide-binding protein (LBP) substituted for LPDP in catalyzing
      lipoprotein neutralization of LTA by HDL. Antibody to LBP inhibited the ability
      of LPDP to induce LTA neutralization by HDL.Thus, lipoproteins can prevent
      macrophage activation by fragments from both gram-positive and gram-negative
      microorganisms.-Grunfeld, C., M. Marshall, J. K. Shigenaga, A. H. Moser, P.
      Tobias, and K. R. Feingold. Lipoproteins inhibit macrophage activation by
      lipoteichoic acid.

PMID- 9925654
TI  - Characterization of apolipoprotein E7 (Glu(244)-->Lys, Glu(245)--->Lys), a mutant
      apolipoprotein E associated with hyperlipidemia and atherosclerosis.
AB  - Previously, a mutant apolipoprotein (apo) E, apolipoprotein E7 (Glu(244)-->Lys,
      Glu(245)--->Lys), has been identified in association with hyperlipidemia and
      atherosclerosis. To investigate the effects of its structural changes on
      lipoprotein metabolisms and its correlation with atherosclerosis, we
      characterized this mutant apoE with respect to its receptor-binding, heparin
      binding, and lipoprotein association. In a competitive binding assay, apoE7.
      dimyristoylphosphatidylcholine displayed a defective binding to the low density
      lipoprotein (LDL) receptor. The concentration of apoE7 required for 50%
      displacement of (125)I-labeled LDL was 0.223 microg/ml, while that for apoE3 was
      0.048 microg/ml. ApoE7 possesses only 23% of normal binding activity. To
      investigate the lipoprotein preference of apoE7, we determined the relative
      amounts of apoE7 in plasma lipoprotein fractions obtained by ultracentrifugation
      or gel filtration. Like human apoE4, apoE7 was preferentially associated with the
      very low density lipoproteins (VLDL). For determination of heparin-binding
      activity, apoVLDL was applied to a heparin-Sepharose affinity column and the
      bound materials were eluted with a salt gradient. The apoE7 was eluted at a
      higher NaCl concentration (157 mm) than apoE3 (126 mm), indicating that this
      mutant has a higher affinity for heparin than does apoE3. While the reduced
      receptor-binding activity indicates delayed clearance of the triglyceride-rich
      lipoproteins, the preferential association of apoE7 with larger-size lipoproteins
      and the stronger interaction with heparin may compensate, to some extent, for the
      delayed clearance of triglyceride-rich lipoproteins. The strong interaction with
      proteoglycans in the arterial wall seems to be one of the possible explanations
      for the association of apoE7 with atherosclerosis.-Yamamura, T., L-M. Dong, and
      A. Yamamoto. Characterization of apolipoprotein E7 (Glu(244)-->Lys, Glu(245)--
      >Lys), a mutant apolipoprotein E associated with hyperlipidemia and
      atherosclerosis.

PMID- 9925655
TI  - Analysis of pristanic acid beta-oxidation intermediates in plasma from healthy
      controls and patients affected with peroxisomal disorders by stable isotope
      dilution gas chromatography mass spectrometry.
AB  - In this paper we report the development of highly sensitive, selective, and
      accurate stable isotope dilution gas chromatography negative chemical ionization
      mass spectrometry (GC-NCI-MS) methods for quantification of peroxisomal beta
      oxidation intermediates of pristanic acid in human plasma: 2,3-pristenic acid, 3
      hydroxypristanic acid, and 3-ketopristanic acid. The carboxylic groups of the
      intermediates were converted into pentafluorobenzyl esters, whereas hydroxyl
      groups were acetylated and ketogroups were methoximized. Hereafter, the samples
      were subjected to clean-up by high performance liquid chromatography. Analyses
      were performed by selected monitoring of the carboxylate anions of the
      derivatives. Control values of all three metabolites were established (2,3
      pristenic acid: 2-48 nm, 3-hydroxypristanic acid: 0.02-0.81 nm, 3-ketopristanic
      acid: 0.07-1.45 nm). A correlation between the concentrations of pristanic acid
      and its intermediates in plasma was found. The diagnostic value of the methods is
      illustrated by measurements of the intermediates in plasma from patients with
      peroxisomal disorders. It is shown that in generalized peroxisomal disorders, the
      absolute concentrations of 2,3-pristenic acid, 3-hydroxypristanic acid, and 3
      ketopristanic acid were comparable to those in the controls, whereas relative to
      the pristanic acid concentrations these intermediates were significantly
      decreased. In bifunctional protein deficiency, elevated levels of 2,3-pristenic
      acid and 3-hydroxypristanic acid were found. 3-Ketopristanic acid, although
      within the normal range, was relatively low when compared to the high pristanic
      acid levels in these patients.-Verhoeven, N. M., D. S. M. Schor, E. A. Struys, E.
      E. W. Jansen, H. J. ten Brink, R. J. A. Wanders, and C. Jakobs. Analysis of
      pristanic acid beta-oxidation intermediates in plasma from healthy controls and
      patients affected with peroxisomal disorders by stable isotope dilution gas
      chromatography mass spectrometry.

PMID- 9925656
TI  - Pregnancy modifies the alpha2-beta-adrenergic receptor functional balance in
      rabbit fat cells.
AB  - The sympathetic nervous system controls lipolysis in fat by activation of four
      adrenergic receptors: beta1, beta2, beta3, and alpha2. During pregnancy, maternal
      metabolism presents anabolic and catabolic phases, characterized by modifications
      of fat responsiveness to catecholamines. The contributions of the four adrenergic
      receptors to adipocyte responsiveness during pregnancy have never been studied.
      Our aim was to evaluate the influence of pregnancy on adrenergic receptor
      mediated lipolysis in rabbit white adipocytes. Functional studies were performed
      using subtype-selective and non-selective adrenergic receptor agonists. Overall
      adrenergic responsiveness was measured with the physiological agonist
      epinephrine. Non-adrenergic agents were used to evaluate different steps of the
      lipolytic cascade. The alpha2- and beta1/beta2-adrenergic receptor numbers were
      determined with selective radioligands. Non-adrenergic agents revealed that
      pregnancy induced an intracytoplasmic modification of the lipolytic cascade in
      inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in
      beta1- and specially beta3-mediated lipolysis. The amounts of adipocyte
      beta1/beta2- and alpha2-adrenergic receptors were increased in pregnant rabbits.
      Epinephrine effects revealed an increased contribution of alpha2-adrenergic
      receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These
      results indicate that pregnancy regulates adipocyte responsiveness to
      catecholamines mainly via the alpha2- and beta3-adrenergic pathways. Pregnancy
      induces an intracytoplasmic modification of the lipolytic cascade, probably via
      hormone-sensitive lipase, with differences according to fat location.-Bousquet
      Melou, A., C. Munoz, J. Galitzky, M. Berlan, and M. Lafontan. Pregnancy modifies
      the alpha2-beta-adrenergic receptor functional balance in rabbit fat cells.

PMID- 9925657
TI  - Presecretory degradation of apolipoprotein [a] is mediated by the proteasome
      pathway.
AB  - Plasma levels of atherogenic lipoprotein [a] (Lp[a]) vary over a 1000-fold range
      and are largely determined by the gene for its unique glycoprotein,
      apolipoprotein [a] (apo[a]). The apo[a] locus comprises more than 100 alleles,
      encoding proteins from <300 to >800 kDa. Using primary baboon hepatocyte
      cultures, we previously demonstrated that differences in the secretion efficiency
      of apo[a] allelic variants contribute to the variation in plasma Lp[a] levels. In
      the current study, we investigated the mechanism of apo[a] presecretory
      degradation. The proteasome inhibitors, acetyl-leucyl-leucyl-norleucinal and
      lactacystin, prevented apo[a] degradation and increased apo[a] secretion.
      Transfection with an HA-tagged ubiquitin construct demonstrated the accumulation
      of ubiquitinated apo[a] in the presence of lactacystin. These results suggest a
      role for the cytoplasmic proteasome in apo[a] proteolysis. Apo[a] that
      accumulated intracellularly in the presence of lactacystin remained sensitive to
      endo-B-N-glucosaminidase H, and apo[a] degradation was reversibly inhibited by
      brefeldin A, suggesting that transport to a post-endoplasmic reticulum (ER) pre
      medial Golgi compartment is required for apo[a] degradation. Newly synthesized
      apo[a] bound to the ER chaperone calnexin and conditions that enhanced this
      interaction prevented apo[a] degradation, suggesting that calnexin can protect
      apo[a] from proteolysis. These studies provide further support for the role of
      the proteasome in endoplasmic reticulum quality control, and expand this role to
      one that influences plasma levels of the atherogenic lipoprotein Lp[a].-White, A.
      L., B. Guerra, J. Wang, and R. E. Lanford. Presecretory degradation of
      apolipoprotein[a] is mediated by the proteasome pathway.

PMID- 9925658
TI  - Effect of variation in the apo A-IV gene on body mass index and fasting and
      postprandial lipids in the European Atherosclerosis Research Study II. EARS
      Group.
AB  - The aims of the study were to investigate associations of the apolipoprotein
      (apo) A-IV polymorphisms Thr347Ser and Gln360His with anthropomorphic
      measurements and fasting and postprandial lipids in subjects participating in the
      European Atherosclerosis Research Study II (EARS II). The allelic frequencies of
      Ser347 and His360 were 0.185 and 0.067, respectively, in the sample as a whole.
      There were no significant differences in rare allele frequency between cases
      (offspring of fathers who suffered a myocardial infarction before the age of 55
      years) and controls. Control subjects who were carriers of Ser347 had
      significantly higher body mass indices (BMIs), waist:hip ratios, total and low
      density lipoprotein cholesterol and triacylglycerol (TG) concentrations (all P <
      or = 0.02) than control subjects who were non-carriers, but these effects were
      not seen in the cases. Control subjects who were carriers of His360 had lower
      BMIs (P = 0.04), cholesterol and TG concentrations (both P < or = 0.07) compared
      to non-carriers, but these effects were not seen in the cases. After consumption
      of an oral fat load, carriers of His360 who were most obese (subjects in the
      third tertile of BMI) had significantly reduced postprandial lipemia (P < 0.03,
      as assessed by area under the curve).-Fisher, R. M., H. Burke, V. Nicaud, C.
      Ehnholm, and S. E. Humphries. Effect of variation in the apoA-IV gene on body
      mass index and fasting and postprandial lipids in the European Atherosclerosis
      Research Study II.

PMID- 9925659
TI  - Relationship between phospholipid transfer protein activity and HDL level and
      size among inbred mouse strains.
AB  - Because of the paucity of data on phospholipid transfer protein (PLTP) activity
      and lipoprotein phospholipid in mouse strains, plasma PLTP activity (PLTA),
      plasma phospholipid and cholesterol, HDL phospholipid and cholesterol, and HDL
      size distribution were determined in 15 inbred mouse strains. The 15 inbred mouse
      strains differed in their relatedness to one another and consisted of six largely
      unrelated groups: Castaneus, Swiss, C57BL, AKR, DBA, and NZB. Lipid and PLTA
      analyses were performed on plasma pools from male and female mice that had fasted
      for 4 h prior to blood draw. Among the representative unrelated strains fed the
      chow diet, there was a highly significant relationship between PLTA and plasma
      phospholipid (r(s) = 0.727, P < 0.01), HDL phospholipid (r(s) = 0.762, P < 0.01),
      HDL cholesterol (r(s) = 0.699, P < 0.02), percentage of large HDL particles (r(s)
      = 0.699, P < 0.02), and HDL peak size (r(s) = 0.776, P < 0.01). Similar results
      were obtained among these strains fed a high fat, high cholesterol diet. PLTA
      increased in all strains fed the high fat diet (chix = 94%, range 6 to 221%).
      Strain SM having relatively low PLTA and HDL was crossed with strain NZB having
      high PLTA and HDL. The F1 progeny from this cross were backcrossed to strain SM
      and 41 male backcross progeny collected. Among these individual backcrossed
      animals, PLTA was highly correlated with plasma phospholipid (r(s) = 0.508, P =
      0.001), HDL phospholipid (r(s) = 0.566, P < 0.001), HDL cholesterol (r(s) =
      0.532, P < 0.001), and percentage of large HDL particles (r(s) = 0.446, P =
      0.020). Therefore, we conclude that PLTP is a determinant of HDL level and size
      in mice.-Albers, J. J., W. Pitman, G. Wolfbauer, M. C. Cheung, H. Kennedy, A-Y.
      Tu, S. M. Marcovina, and B. Paigen. Relationship between phospholipid transfer
      protein activity and HDL level and size among inbred mouse strains.

PMID- 9925660
TI  - Percent cholesterol absorption in normal women and men quantified with dual
      stable isotopic tracers and negative ion mass spectrometry.
AB  - Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80
      years while consuming diets generally low in cholesterol (mean intake = 226 +/-
      126 mg/day). A new dual stable isotope method was used where a cholesterol tracer
      containing 6 extra mass units was given intravenously and another tracer with 5
      extra mass units was given orally during a standard test meal. The ratio of
      tracers in plasma was determined by negative ion mass spectrometry of
      pentafluorobenzoyl sterol esters. Absorption values ranged widely from 29.0% to
      80.1% with mean 56.2 +/- 12.1 (SD) %. Cholesterol absorption was significantly
      increased in African-Americans (63.4 +/- 11.8% vs. 55.1 +/- 11.9%, P = 0.027) but
      was similar for women (53.3 +/- 11.9%) and men (57.6 +/- 12.1%). It was not
      related to plasma lipoproteins, age, apoE3/E3 or E3/E4 genotype, or chronic
      dietary intake of energy, fat, or cholesterol quantitated from 7- day food
      records. However, dietary cholesterol intake was positively related to plasma
      cholesterol (P = 0.036) and triglycerides (P = 0.026). The milligram amount of
      dietary cholesterol absorbed (but not percent absorption) was positively
      correlated with fasting plasma insulin (r = 0.525, P < 0.0001), C-peptide (r =
      0.367, P = 0.0003) and glucagon (r = 0.421, P < 0.0001) independent of gender,
      body fat percent and age.The efficiency of intestinal cholesterol absorption and
      the milligram amount of dietary cholesterol absorbed were not related to plasma
      cholesterol or LDL cholesterol in individuals consuming a low-cholesterol low-fat
      diet. The dominant factor determining dietary cholesterol absorption was intake
      rather than absorption efficiency. Dietary cholesterol and fat were strongly and
      independently related to hormonal measures of insulin resistance.-Bosner, M. S.,
      L. G. Lange, W. F. Stenson, and R. E. Ostlund, Jr. Percent cholesterol absorption
      in normal women and men quantified with dual stable isotopic tracers and negative
      ion mass spectrometry.

PMID- 9925661
TI  - Retinyl esters are hydrolyzed in early endosomes of J774 macrophages.
AB  - The aim of the current study was to identify the subcellular compartment(s)
      responsible for the hydrolysis of chylomicron remnant-retinyl esters, in J774.1
      cells. The cells were incubated with medium containing chylomicron remnant
      [(3)H]retinyl ester. Subcellular fractionation was used to separate early
      endosomes from late endosomes and lysosomes. About 26% and 80% of the total
      [(3)H]retinyl esters taken up by the J774 cells were hydrolyzed after 10 min and
      60 min of chase, respectively. In the early endosomes, there was a 4-fold
      increase of radioactivity (nearly all radioactivity associated with retinyl
      esters) during the first 10 min of chase. The radioactivity in early endosomes
      was reduced by 43% from 10 min to 60 min and remained stable from 60 to 180 min
      of chase. From 10 to 60 min the amount of retinol in early endosomes increased
      from 44% to 82%, indicating an efficient hydrolysis of retinyl esters. Less than
      10% and 5% of the total cell-associated radioactivity was found in the late
      endosomes and lysosomes during the entire chase period. In the chase medium, 84%
      of the total amount of retinoid released during 180 min was present already after
      10 min. The percentage of retinol in the medium increased from 25% to 82% during
      incubation from 10 to 180 min. These data suggest that retinyl esters are
      endocytosed together with the chylomicron remnant particle and hydrolyzed in the
      early endosomes in this cell model.-Hagen, E., A. M. Myhre, T. E. Tjelle, T.
      Berg, and K. R. Norum. Retinyl esters are hydrolyzed in early endosomes of J774
      macrophages.

PMID- 9925662
TI  - The apolipoprotein B R3531C mutation. Characteristics of 24 subjects from 9
      kindreds.
AB  - Familial ligand-defective apolipoprotein B (apoB) is a group of disorders caused
      by mutations in the apoB gene. In this report the R3531C mutation is
      characterized further using a monoclonal antibody MB19/dynamic laser light
      scattering technique to measure ratios of Cys(3531) to normal low density
      lipoprotein (LDL) particles. All six subjects studied showed a preferential
      accumulation of particles carrying the defective apoB allotype. We determined
      binding properties of LDL from R3531C heterozygotes by measurement of high
      affinity binding to LDL receptors on fibroblasts and its ability promote growth
      of U937 cells. LDL from R3531C heterozygotes, compared to normal LDL, had 49.3%
      of the binding affinity and was 74% as effective in a U937 cell proliferation
      assay. To identify new probands, we screened 2570 subjects for the R3531C
      mutation. Nine probands were found with 15 affected relatives. Of the seven
      haplotypes we uncovered, two were novel, while five were identical to one
      initially reported as associated with Cys3531. Three silent mutations were
      detected also: T3540T, N3542N and T3552T. Analysis of lipid profiles of R3531C
      families showed, as with the R3500Q mutation, variable expression of the
      phenotype, modulated by environmental and other genetic factors. Both mutations
      tend to produce lower plasma levels of LDL in affected subjects than do defects
      of the LDL receptor (familial hypercholesterolemia, FH). This study shows that
      the Cys(3531) LDL particles are not only defective at binding to the LDL
      receptor, as determined by two separate methods, but that in all cases they
      accumulate preferentially compared to the normal allotype.-Pullinger, C. R., D.
      Gaffney, M. M. Gutierrez, M. J. Malloy, V. N. Schumaker, C. J. Packard, and J. P.
      Kane. Apolipoprotein B R3531C mutation: characteristics of 24 subjects from 9
      kindreds. .

PMID- 9925663
TI  - Cholesterol efflux from Fu5AH cells to the serum of patients with Alagille
      syndrome. Importance of the hdl-phospholipids/free cholesterol ratio and of the
      hdl size distribution.
AB  - We have previously described the lipoprotein abnormalities in cholestatic
      children with paucity of interlobular bile ducts (PILBD), and we have shown that
      two different profiles emerged among these patients, depending on the level of
      lecithin:cholesterol acyltransferase (LCAT) activity. Reduced LCAT activity was
      associated with hypo-alpha-lipoproteinemia (group I) whereas normal LCAT activity
      was associated with hyper-alpha-lipoproteinemia (group II). In both groups, high
      density lipoproteins (HDL) were enriched with phospholipids and LpA-I particles
      were predominant. Here, we have investigated the ability of serum and of isolated
      HDL, obtained from PILBD and control subjects, to promote cellular cholesterol
      efflux, from Fu5AH rat hepatoma cells. The mean fractional efflux to 5% serum in
      each group was, on average, following the differences in HDL concentrations
      (control: 30.1 +/- 4.2%; group I: 23.7 +/- 7.9%, ns; group II: 44.2 +/- 6.5%, P <
      0.001). The variations in efflux values in group II were positively correlated to
      the variations in HDL-PL concentrations (P < 0.0001) and in HDL-PL to serum apo
      AI ratio (P < 0.003). By contrast, the variation in efflux in group I was only
      positively related to the large range of HDL-PL to free cholesterol (FC) ratio
      values (P < 0.0004). Fractional efflux to isolated HDL, measured at a constant
      HDL-PL amount, confirmed this relationship (P < 0.0001). Two-dimensional gel
      electrophoresis of the HDL size and apo A-I distribution in serum, revealed that
      small size HDL(3) and pre-beta HDL were predominant in the serum of patients from
      group I, especially those exhibiting low HDL-PL to FC ratio, whereas in the serum
      of patients from group II, both small HDL(3) and large HDL2 were present. These
      results suggest that a combination of an imbalance between phospholipids and free
      cholesterol in the HDL particles and a deficit in large acceptors of cholesterol
      will be responsible for an impairment of cellular cholesterol efflux in PILBD
      patients with reduced lecithin:cholesterol acyltransferase activity.-Davit
      Spraul, A., V. Atger, M. L. Pourci, M. Hadchouel, A. Legrand, and N. Moatti.
      Cholesterol efflux from Fu5AH cells in the serum of patients with Alagille
      syndrome: importance of the HDL-phospholipids/free cholesterol ratio and of the
      HDL size distribution.

PMID- 9925664
TI  - In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a
      high level of apoE but is inhibited by excess apoE.
AB  - To investigate the quantitative requirement for apolipoprotein (apo) E in the
      clearance of lipoproteins via the non-low density lipoprotein (LDL) receptor
      mediated pathway, human APOE was overexpressed at various levels in the livers of
      mice deficient for both the endogenous Apoe and Ldlr genes (Apoe -/-. Ldlr -/-)
      using adenovirus-mediated gene transfer. We found that a low level of APOE
      expression, that was capable of reducing the hyperlipidemia in Apoe -/- mice, did
      not result in a reduction of the hyperlipidemia in Apoe -/-. Ldlr -/- mice.
      Surpisingly, a very high level of APOE expression also did not result in a
      reduction of hypercholesterolemia in Apoe -/-. Ldlr -/- mice, despite very high
      levels of circulating apoE (>160 mg/dl). Only a moderately high level of APOE
      expression resulted in a reduction of serum cholesterol level (from 35.2 +/- 6.7
      to 14.6 +/- 2.3 mmol/l) and the disappearance of VLDL from the serum. Moreover,
      the very high level of APOE expression resulted in a severe hypertriglyceridemia
      in Apoe -/-. Ldlr -/- mice and not Apoe -/- mice (25.7 +/- 8.9 and 2.2 +/- 1.8
      mmol/l, respectively). This hypertriglyceridemia was associated with an APOE
      induced increase in the VLDL triglyceride production rate and an inhibition of
      VLDL-triglyceride lipolysis. We conclude from these data that, for efficient
      clearance, the non-LDL receptor-mediated pathway requires a higher level of APOE
      expression as compared to the LDL receptor, but is more sensitive to an APOE
      induced increase in VLDL production and inhibition of VLDL-triglyceride
      lipolysis.-van Dijk, K. W., B. J. M. Van Vlijmen, H. B. van't Hof, A. van der
      Zee, S. Santamarina-Fojo, T. J. C. van Berkel, L. M. Havekes, and M. H. Hofker.
      In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a
      high level of apoE but is inhibited by excess APOE.

PMID- 9925665
TI  - Ability of reconstituted high density lipoproteins to inhibit cytokine-induced
      expression of vascular cell adhesion molecule-1 in human umbilical vein
      endothelial cells.
AB  - Previous studies have shown that both high density lipoproteins (HDL) isolated
      from human plasma and reconstituted HDL (rHDL) are effective inhibitors of
      adhesion molecule expression in human endothelial cells. In this study rHDL have
      been used to investigate whether HDL particle shape, size, apolipoprotein
      composition or lipid composition are important determinants of the ability of HDL
      to inhibit the TNF-alpha induced expression of vascular cell adhesion molecule-1
      (VCAM-1) in human umbilical vein endothelial cells (HUVECs). On the basis of
      these studies it is possible to draw several firm conclusions. i) Neither
      phospholipid-containing vesicles nor lipid-free apolipoprotein (apo) A-I inhibit
      VCAM-1 expression in HUVECs. ii) Simple discoidal complexes containing only
      phospholipid and apoA-I (discoidal (A-I)rHDL) are sufficient to inhibit the TNF
      alpha-induced expression of VCAM-1 in HUVECs. iii) Spherical apoA-I-containing
      rHDL (spherical (A-I)rHDL) are superior to discoidal (A-I)rHDL as inhibitors. iv)
      The particle size of spherical (A-I)rHDL has no influence on the inhibition. v)
      Spherical rHDL that contain apoA-I are superior as inhibitors of VCAM-1 to those
      containing apoA-II when the rHDL preparations are equated for apolipoprotein
      molarity. However, when compared at equivalent particle molarities, this
      difference is no longer apparent. vi) Replacement of cholesteryl esters with
      triglyceride in the core of spherical (A-I)rHDL has no effect on the ability of
      these particles to inhibit VCAM-1 expression. From these results it is tempting
      to speculate that variations in inhibitory activity may contribute to the
      variations observed in the anti-atherogenicity of different HDL subpopulations.
      Baker, P. W., K-A. Rye, J. R. Gamble, M. A. Vadas, and P. J. Barter. Ability of
      reconstituted high density lipoproteins to inhibit cytokine-induced expression of
      vascular cell adhesion molecule-1 in human umbilical vein endothelial cells.

PMID- 9925666
TI  - A novel kringle-4 number-based recombinant apo[a] standard for human apo[a]
      phenotyping.
AB  - Apolipoprotein[a] phenotyping is a critically important method to explore the
      role of kringle-4 repeat number as a modulator of lipoprotein[a]-associated
      cardiovascular risk. The availability of a kringle-4 number-based reference
      standard is therefore necessary for a reliable and generally accepted
      classification of apo[a] phenotypes. We propose here a battery of recombinant
      apo[a] isoforms that may be used as the reference standard in various gel
      systems. Five plasmids encoding for r-apo[a] containing a known number (n = 9,
      13, 17, 25, 33) of plasminogen-like kringle-4 copies were constructed, and
      transfected into the human embryonic kidney cell line 293. The electrophoretic
      mobility of the recombinant apo[a] isoforms expressed by these cells in a hollow
      fiber bioreactor was determined after reduction by SDS-gel (agarose, acrylamide
      or a mixture of both) electrophoresis and immunoblotting using an antibody
      specific for human apo[a]. The equation of the linear relationship between log r
      apo[a] kringle number and relative migration was used to determine the isoform
      size of apo[a] in normal human plasma. A very good correlation (r = 0.97) was
      found with the genotype (pulsed-field gel eletrophoresis of kpnI-digested
      restriction fragments of genomic DNA) and among electrophoretic methods. The
      proposed recombinant standard offers the possibility to identify apo[a] isoforms
      within a large range of molecular sizes, 9 to 33 kringle-4 copies, using simple
      electrophoretic techniques and a nomenclature based on its molecular structure,
      i.e., the number of kringle-4 repeats.-Angles-Cano, E., S. Loyau, G. Cardoso
      Saldana, R. Couderc, and P. Gillery. A novel kringle-4 number-based recombinant
      apo[a] standard for human apo[a] phenotyping.

PMID- 9925667
TI  - The next war....

PMID- 9925668
TI  - Patients' bill of rights offers welcomed protection of patients, nurses, and
      emergency departments.

PMID- 9925669
TI  - Additional SANE program listing.

PMID- 9925670
TI  - More on DNR: Agonizing decisions, haunting questions.

PMID- 9925671
TI  - A 42-year-old man with rhabdomyolysis from substance abuse and minor trauma.
AB  - During initial assessment and care of this patient, an element of disbelief of
      the patient's inability to move his extremities was expressed. Manifestation of a
      severe injury such as that affecting the spinal cord after an extended period of
      time would be unusual. All other causes of altered motor function should be
      promptly investigated. The importance of listening and believing the patient was
      reinforced with this case. Many excellent clinicians will state that 80% of the
      diagnosis comes from the patient history. The physical examination and diagnostic
      tests should only validate what has been obtained from listening to the patient.
      Although we had cared for patients with hyperkalemia in the past, this case
      expanded our knowledge about a range of therapies available to treat this
      electrolyte abnormality and the physiologic mechanisms for each. We are impressed
      with the number of mechanisms and medications that can contribute to the
      development of rhabdomyolysis. Caregivers are at risk of assuming that the
      patient's condition fits the category to which they have been triaged. Keeping an
      open mind concerning the range of rationale for patient signs and symptoms is
      important.

PMID- 9925672
TI  - Priorities for research in Emergency Medical Services for Children: results of a
      consensus conference. EMSC Research Agenda Consensus Committee, National EMSC
      Resource Alliance.
AB  - STUDY OBJECTIVE: The study objective was to arrive at a consensus on the
      priorities for future research in Emergency Medical Services for Children (EMSC).
      METHODS: A consensus group was convened using the Rand'-UCLA Consensus Process.
      The group took part in a 3-phase process. Phase I involved reviewing a compendium
      of relevant research articles and answering a mailed questionnaire. Panel members
      were asked to prioritize topics based on the 1993 Institute of Medicine Report on
      Emergency Medical Services for Children. Participants were asked to rate each
      topic based on the significance of the research and whether the topic would (1)
      improve general knowledge, (2) change behavior, (3) improve health, (4) decrease
      the cost of care, or (5) change public policy. A 4-point Likert scale was used.
      They were also asked in the research would require a multicenter study and if the
      research were feasible. Round II of the study involved a meeting of the panel,
      where the results of Round I were discussed and the topics reprioritized. The
      topics were given a rank order and a final ranking was done in Round III.
      RESULTS: The panel considered a list of 32 topics and these were combined and
      reworded to give them more precise meaning. Several new topics were also added.
      Fifteen topics were given a rank order and placed within the 7 broad categories
      of the Institute of Medicine report. Clinical aspects of emergency care systems
      organization, configuration and operation and injury prevention were given high
      priority rankings. The first 5 topics were very close in point-rank order.
      CONCLUSION: The panel was able to develop a list of important topics for future
      research in EMSC that can be used by foundations, governmental agencies, and
      others in setting a research agenda for EMSC.

PMID- 9925673
TI  - ED case managers: one large teaching hospital's experience.

PMID- 9925674
TI  - The need for increasing organ donation among African Americans and Hispanic
      Americans: an overview.
AB  - Other groups in the United States could no doubt benefit from attention to the
      issue of organ donation, but I was unable to collect any data on the cultural
      beliefs and perspectives of the Asian American population, for example, regarding
      organ donation. We know that most Asian countries, such as Japan, have only
      recently begun organ donation programs. The United States represents one of the
      most culturally heterogeneous populations in the world today. Health care workers
      are called on every day of their lives to overcome cultural or ethnic
      differences, and at no point during the health care process is culturally
      competent care more necessary than during the final hours of a person's life.
      Organ donation is a question that should be asked of every family that loses a
      loved one so that they can have the opportunity to give of themselves in an
      effort to save the lives of others. The lives of many persons are solely
      dependent upon the successful retrieval of an organ donor. Therefore, being well
      informed and effective with potential donor families is imperative for emergency
      nurses. Editor's note: This manuscript is an academic paper that was written at
      the University of Wisconsin in Milwaukee, where the author is a student nurse.
      When the manuscript and educational displays were completed, representatives from
      the Wisconsin Donor Network attended a reception at the school held during
      National Organ and Tissue Donor Awareness Week. Accompanying them was a young 27
      year-old recipient of a heart transplant. As a result of his visit, faculty and
      students (even "skeptics") were inspired to become organ or tissue donors by
      signing the back of their driver's licenses and became committed to educating
      others about the issue.

PMID- 9925675
TI  - Update on diabetes medications.

PMID- 9925676
TI  - Chart management: prioritizing and organizing.

PMID- 9925677
TI  - A difficult case involving a bradycardic patient.

PMID- 9925678
TI  - From the Feds.

PMID- 9925679
TI  - Y2K: what you don't know can hurt you.

PMID- 9925680
TI  - Nursing judgment--is it alive?

PMID- 9925681
TI  - Providing thank-you letters for guest speakers' portfolios.

PMID- 9925682
TI  - Hypothermia in a 7-year-old boy: the Current Creek rescue.

PMID- 9925683
TI  - Is Trendelenburg a wise choice?

PMID- 9925684
TI  - IAFN Sixth Annual Scientific Assembly highlights.

PMID- 9925685
TI  - External pelvic stabilization: nursing implications.

PMID- 9925686
TI  - A 45-year-old man with dizziness.

PMID- 9925687
TI  - International award winner works in enforced solitude: implications for health
      care providers. Interview by Marlene Jezierski.

PMID- 9925688
TI  - The last shot.

PMID- 9925689
TI  - CEN Review Questions.

PMID- 9925690
TI  - Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent
      bleeding, surgery, and length of hospital stay.
AB  - BACKGROUND: The impact of upper endoscopy in patients with upper gastrointestinal
      hemorrhage treated in community practice is unknown. Thus we examined the
      effectiveness of endoscopy performed within 24 hours of admission (early
      endoscopy). METHODS: Medical records of 909 consecutive hospitalized patients
      with upper gastrointestinal hemorrhage who underwent endoscopy at 13 hospitals in
      a large metropolitan area were reviewed. We evaluated unadjusted and severity
      adjusted associations of early endoscopy with recurrent bleeding or surgery to
      control hemorrhage, length of hospital stay, and associations of endoscopic
      therapy in patients with bleeding ulcers or varices. RESULTS: Early endoscopy was
      performed in 64% of patients and compared with delayed endoscopy and was
      associated with clinically significant reductions in adjusted risk of recurrent
      bleeding or surgery (odds ratio [OR] 0.70: 95% CI [0.44, 1.13]) and a 31%
      decrease in adjusted length of stay (95% CI: [24%, 37%]). In patients at high
      risk for recurrent bleeding, the use of early endoscopic therapy to control
      hemorrhage was associated with reductions in recurrent bleeding or surgery (OR
      0.21: 95% CI [0.10, 0.47]) and length of stay (-31%: 95% CI [-44%, -14%).
      CONCLUSION: In this study of community-based practice, the routine use of
      endoscopy, and in selected cases endoscopic therapy, performed early in the
      clinical course of patients with upper gastrointestinal hemorrhage was associated
      with reductions in length of stay and, possibly, the risk of recurrent bleeding
      and surgery.

PMID- 9925691
TI  - Acute major gastrointestinal hemorrhage in inflammatory bowel disease.
AB  - BACKGROUND: Acute major gastrointestinal hemorrhage is uncommon in inflammatory
      bowel disease. METHODS: We characterized the clinical features and course of such
      hemorrhage in patients at our institution from 1989 to 1996. RESULTS: Thirty-one
      patients had acute lower gastrointestinal bleeding from inflammatory bowel
      disease and one had upper gastrointestinal bleeding from duodenal Crohn's
      disease. Three patients had ulcerative colitis and 28 had Crohn's disease,
      representing 0.1% of admissions for ulcerative colitis and 1.2% for Crohn's
      disease. In addition, another patient bled from an ileal J-pouch. In patients
      with Crohn's disease, the site of bleeding was duodenal in 1, small intestinal in
      9, ileocolonic in 8, and colonic in 10. All ulcerative colitis patients had
      pancolitis. Medical therapy was initiated in 27 patients, including endoscopic
      therapy in 3. Five patients underwent surgery immediately, and 7 medically
      treated patients eventually required surgery for ongoing or recurrent bleeding.
      CONCLUSIONS: Acute major gastrointestinal bleeding is uncommon in inflammatory
      bowel disease. Most cases are due to Crohn's disease, without a predilection for
      site of involvement. The presence of an endoscopically treatable lesion is
      uncommon, and surgery is required in less than half of cases during the initial
      hospitalization. Recurrent hemorrhage is not rare, and for these cases surgery
      may be the most appropriate treatment.

PMID- 9925692
TI  - Effectiveness and patient satisfaction with screening flexible sigmoidoscopy
      performed by registered nurses.
AB  - BACKGROUND: Our aim was to compare the effectiveness and patient satisfaction
      with flexible sigmoidoscopy performed by a registered nurse, general surgeons,
      and gastroenterology fellows. METHODS: Consecutive outpatients referred for
      sigmoidoscopy were assigned to have the procedure performed by the first
      available provider. Depth of insertion of the sigmoidoscope, complications,
      duration of the procedure, and percentage of patients with adenomas were
      recorded. After the procedure, patients completed a validated patient
      satisfaction questionnaire. RESULTS: Mean depth of insertion was less for general
      surgeons compared with the nurse and gastroenterology fellows (50 vs 53 vs 54 cm,
      respectively; p = 0.01). Mean duration of procedure was longer for the nurse
      compared with general surgeons and gastroenterology fellows (8.3 vs 7.6 vs 6.8
      min, respectively; p = 0.0001). Percentage of patients with adenomas was similar
      among patients who underwent sigmoidoscopy by the endoscopists (7% vs 8% vs 9%; p
      = 0.81). No differences were detected between endoscopists for overall
      satisfaction (p = 0.60), technical skills of the endoscopist (p = 0.58),
      communication skills of the endoscopist (p = 0.61), or interpersonal skills of
      the endoscopist (p = 0.59). CONCLUSION: No clinically significant differences in
      effectiveness or patient satisfaction were detected with flexible sigmoidoscopy
      performed by a registered nurse, general surgeons, or gastroenterology fellows.

PMID- 9925693
TI  - Licensure, use, and training of paramedical personnel to perform screening
      flexible sigmoidoscopy.
AB  - BACKGROUND: The purpose of this study was to assess the state board of nursing
      guidelines about the performance of flexible sigmoidoscopy by nurses and to
      determine the current use and training of paramedical personnel in flexible
      sigmoidoscopy at gastroenterology fellowship programs in the United States.
      METHODS: Separate one-page questionnaires were sent to state boards of nursing
      and directors of endoscopy at gastroenterology fellowship programs in the United
      States. RESULTS: Twenty percent (10 of 50) of state boards of nursing explicitly
      approve the performance of sigmoidoscopy by registered nurses, and 50% (25 of 50)
      explicitly approve the practice by nurse practitioners. Forty-six percent (23 of
      50) of state boards of nursing have no written policy but allow nurses to use a
      "decision making model" to determine whether the performance of sigmoidoscopy is
      allowed. Fifteen percent (24 of 164) of gastroenterology fellowship programs in
      the United States use paramedical personnel to perform flexible sigmoidoscopy.
      Sixty-three percent (15 of 24) of these programs started since 1995, and 67% (16
      of 24) require that the paramedical personnel perform 50 or more supervised
      sigmoidoscopies during their training. Forty-five percent (5 of 11) of programs
      with physician assistants/nurse practitioners use these personnel to perform
      colonoscopy or endoscopy. CONCLUSIONS: Nurses are allowed to perform flexible
      sigmoidoscopy in most states based on current state board of nursing guidelines.
      The use of paramedical personnel to perform endoscopic procedures is increasing
      rapidly.

PMID- 9925694
TI  - Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett's
      esophagus with high-grade dysplasia.
AB  - BACKGROUND: The optimal management of high-grade dysplasia in patients with
      Barrett's esophagus is controversial. The aim of this study was to assess the
      prevalence of unsuspected carcinoma at esophagectomy in patients with Barrett's
      esophagus with high-grade dysplasia after endoscopic surveillance with jumbo
      biopsy forceps compared with standard biopsy forceps. METHODS: Twelve patients
      with high-grade dysplasia in Barrett's esophagus without gross or microscopic
      evidence of carcinoma underwent esophagectomy after preoperative endoscopy with 4
      quadrant jumbo biopsies at 2-cm intervals. The findings in this group were
      compared with those in a group of patients with Barrett's esophagus who underwent
      esophagectomy for high-grade dysplasia after biopsies obtained at 2-cm intervals
      with standard biopsy forceps. RESULTS: Unsuspected cancer was found in 4 of 12
      (33%) patients in the jumbo biopsy group compared with 6 of 16 (38%) in the
      standard biopsy group (p = NS). All 6 cancers in the standard biopsy group were
      intramucosal, whereas 2 were intramucosal and 2 were submucosal in the jumbo
      biopsy group. No patients in either group had lymph node metastases. CONCLUSIONS:
      Unsuspected cancer is found frequently in patients with Barrett's esophagus who
      are undergoing esophagectomy for high-grade dysplasia despite the use of a
      rigorous jumbo biopsy protocol. Esophageal resection is still indicated in
      appropriately selected patients with high-grade dysplasia until better markers of
      cancer risk are available.

PMID- 9925695
TI  - Influence of endoscopic biopsy forceps characteristics on tissue specimens:
      results of a prospective randomized study.
AB  - BACKGROUND: A large variety of endoscopic biopsy forceps are commercially
      available. However, little is known regarding the influence of forceps
      characteristics such as disposability, size, shape, and presence of a needle on
      the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in
      a prospective, randomized, pathologist-blinded study the performance of different
      biopsy forceps. METHODS: Twelve biopsy forceps were tested, 6 each at upper
      endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps,
      for a total of 12 specimens per patient. The tissue samples were examined for the
      following parameters: weight (mg), size (mm3), depth, crush artifact, sheering
      effect, and adequacy of the specimens for histologic information (0 = inadequate,
      1 = suboptimal, and 2 = adequate). RESULTS: Fifty-five patients undergoing
      routine upper or lower gastrointestinal endoscopy were included in the study, and
      a total of 624 tissue samples were available for analysis. Overall, disposable
      forceps provided specimens of greater size and depth. At upper endoscopy,
      alligator-shaped forceps improved the depth of the sample as did the absence of a
      needle within the cup. These factors, however, had no impact on the specimens
      obtained at colonoscopy. When the adequacy of the specimens was assessed for
      histologic diagnosis, no significant difference was noted between any of the
      individual forceps, although collectively oval-shaped forceps were superior to
      alligator-shaped forceps at colonoscopy. CONCLUSIONS: The biopsy forceps
      currently available in the market are equally efficient in providing histologic
      diagnosis. The primary consideration when selecting an endoscopic biopsy forceps,
      therefore, should be the cost and ease of use and not any perceived advantage in
      performance.

PMID- 9925696
TI  - Endosonographic diagnosis of submucosal upper gastrointestinal tract lesions and
      large fold gastropathies by catheter ultrasound probe.
AB  - BACKGROUND: The unique ability of EUS to depict wall layers makes it possible to
      accurately evaluate submucosal lesions of the digestive tract and large-fold
      gastropathies. Although EUS requires a second endoscopic examination, miniature
      US probes introduced through the accessory channel of a conventional endoscope
      permit US examination during routine endoscopy. METHODS: By means of catheter
      probe sonography and conventional EUS, we evaluated 33 patients with a
      radiographic or endoscopic finding of a submucosal lesion of the upper GI tract
      or with large-fold gastropathies and histologically negative biopsies obtained at
      a previous endoscopy. A miniature multifrequency probe was used for catheter
      probe sonography. RESULTS: For 25 submucosal lesions catheter probe sonography
      results were superimposable on those obtained with EUS. In evaluating submucosal
      lesions, catheter probe sonography yielded the same results as conventional EUS
      in terms of depiction, measurement, and identification of the originating layer
      of the tumor. In the study of 8 large-fold gastropathies, catheter probe
      sonography missed the presence of ascites and enlarged lymph nodes in a case of
      gastric linitis, but produced the same results as conventional EUS in the other
      cases. CONCLUSIONS: For the evaluation of benign submucosal lesions and large
      fold gastropathies, catheter probe sonography appears to be sufficient and could
      thus replace conventional EUS for these indications.

PMID- 9925697
TI  - Treatment of gastric tumors by endoscopic mucosal resection with a ligating
      device.
AB  - BACKGROUND: This study attempted to determine the indication for endoscopic
      mucosal resection with a ligating device (EMRL) and to assess the efficacy of
      radical (complete) resection of early gastric carcinoma and adenoma. METHODS:
      Sixteen patients with early gastric carcinoma (17 lesions) and 21 patients with
      gastric adenoma (23 lesions) underwent EMRL with an endoscope with a ligating
      device. After epinephrine solution was injected into the submucosa, the lesions
      were aspirated, ligated, and resected. RESULTS: Twelve of 17 early carcinomas
      (70.6%) and 18 of 23 adenomas (78.3%) were radically resected by EMRL. The
      average size of the resected specimens was 12.8 x 11.0 mm. The rate of successful
      radical resection by EMRL, including piecemeal resection, was 100% (15/15) for
      lesions located in the antrum, 80% (4/5) in the angle, 61.1% (11/18) in the body,
      and 0% (0/2) for lesions at the cardia. Repeat EMRL was performed successfully in
      cases of partial resection (n = 3). No serious complication was encountered. No
      recurrence of the tumors was identified in cases of radical resection during a
      median follow-up period of 22.8 months. CONCLUSION: EMRL is suitable for the
      treatment of gastric tumorous lesions. For the treatment of early carcinoma, well
      differentiated mucosal carcinomas smaller than 10 mm located in the distal
      stomach represent the best indication for EMRL.

PMID- 9925698
TI  - Bile duct wall thickness measured by intraductal US in patients who have not
      undergone previous biliary drainage.
AB  - BACKGROUND: We investigated the bile duct wall thickness measured on intraductal
      US in patients who had not undergone biliary drainage, with special attention to
      the influence of cancer at the distal bile duct, bile duct stones, obstructive
      jaundice, longitudinal cancer extension, and primary sclerosing cholangitis on
      wall thickness. METHODS: The study included 183 patients. Patients who had
      undergone previous biliary drainage were excluded. Intraductal US was performed
      by the transpapillary route with use of a thin-caliber ultrasonic probe (2.0 mm
      diameter, 20 MHz frequency). The bile duct wall thickness (width of the inside
      hypoechoic layer) was retrospectively measured on US images. RESULTS: Bile duct
      wall thicknesses of the common hepatic duct for the control group (n = 95),
      cancer at the distal bile duct group (n = 9), bile duct stone group (n = 56), and
      obstructive jaundice group (n = 17) were 0.6 +/- 0.3 mm (mean +/- SD), 0.8 +/-
      0.5 mm, 0.8 +/- 0.6 mm, and 0.8 +/- 0. 5 mm, respectively. No significant
      differences (p > 0.05) were found between them. However, wall thickness for the
      cancer extension to the common hepatic duct group (n = 4, 2.0 +/- 0.4 mm) and
      sclerosing cholangitis group (n = 2, 2.5 +/- 0.4 mm) were significantly greater
      than in the other groups (p < 0.005). CONCLUSIONS: In patients who have not
      undergone previous biliary drainage, the bile duct wall thickness was not thicker
      in patients with obstructive jaundice. However, the duct wall was significantly
      thicker in patients with either longitudinal cancer extension or primary
      sclerosing cholangitis compared with that of other groups.

PMID- 9925699
TI  - Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic
      duct unrelated to intrahepatic stones.
AB  - BACKGROUND: Intrahepatic duct strictures are usually caused by intrahepatic duct
      stones and cholangitis. However, focal strictures of the intrahepatic duct
      unrelated to intrahepatic stones often pose diagnostic problems. This study was
      undertaken to prospectively evaluate the usefulness of percutaneous transhepatic
      cholangioscopy in patients with focal intrahepatic duct stricture and no evidence
      of a stone. METHODS: Seventeen patients with focal strictures of the intrahepatic
      duct without any evidence of a stone were included. Percutaneous transhepatic
      cholangioscopic examination including procurement of biopsy specimens was
      performed after percutaneous transhepatic biliary drainage. RESULTS: A
      histopathologic diagnosis was obtained in all patients (9 adenocarcinomas, 1
      squamous cell carcinoma, 2 hepatocellular carcinomas, 2 adenomas, and 3 benign
      strictures). Of the 9 patients with bile duct adenocarcinoma, 8 underwent surgery
      and a curative resection was possible in 7 patients (88%). Five patients (63%)
      had early-stage bile duct cancer in which cancer invasion was limited to the
      mucosa or fibromuscular layer and there was no evidence of lymph node metastasis.
      CONCLUSIONS: Percutaneous transhepatic cholangioscopy in patients with focal
      stricture of the intrahepatic duct unrelated to choledocholithiasis is useful for
      diagnosis including the detection of early bile duct cancer.

PMID- 9925700
TI  - Clinical application of a new disposable lithotripter: a prospective multicenter
      study.
AB  - BACKGROUND: Mechanical lithotripsy has become a well-accepted method of bile duct
      stone fragmentation and removal. The Olympus lithotripter (Olympus American,
      Melville, NY) is the standard reusable lithotripter at the institutions that
      participated in this study. A disposable device with a preassembled pistol grip
      may perform equally well and facilitate operation. METHODS: Twenty patients with
      bile duct stones were evaluated as part of a multicenter prospective study. Data
      were obtained regarding stone size and number, bile duct diameter, and
      configuration, ease of cannulation, basket function, stone capture and crushing
      success, and complications. RESULTS: The maximum stone size averaged 16.5 +/- 1.2
      mm (range 10 to 30 mm). Sixteen patients had multiple stones (median 5, range 2
      to 12). The mean bile duct diameter was 20.5 +/- 1.5 mm (range 12 to 38 mm).
      Cannulation was successful in all within 5 attempts. Basket deployment failed in
      1 patient because of stone size and the basket was misshapen in 14. Bile duct
      clearance was complete in 16 subjects (80%), incomplete in 2 patients, and failed
      in 2 patients. Abnormal duct configuration (sigmoid, stricture) was noted in 2 of
      4 patients with failed capture and 7 of 16 patients with successful clearance. No
      statistically significant difference was observed between the bile duct diameter,
      maximum stone size, number of stones, and successful clearance. CONCLUSION: The
      disposable lithotripter is easy to use and, compared with the published results
      for the reusable lithotripter, performs almost as well.

PMID- 9925701
TI  - Prospective assessment of the risk of bacteremia in cirrhotic patients undergoing
      lower intestinal endoscopy.
AB  - BACKGROUND: Patients who have prosthetic heart valves, previous history of
      endocarditis, and surgically constructed systemic-pulmonary shunts or conduits
      should receive prophylactic antibiotics before colonoscopy. The usefulness of
      this approach in cirrhotic patients remains unknown. The present study
      prospectively assesses the incidence of bacteremia in these patients. METHODS:
      Lower intestinal endoscopy was performed in 58 cirrhotic patients. Two blood
      samples were obtained from every patient (just before endoscopy and within 5
      minutes of withdrawal of the endoscope) and were incubated for 7 days and
      examined daily for growth of bacteria. Patients were closely monitored for 72
      hours after endoscopy to detect the development of infectious complications.
      RESULTS: Only 6 cultures from 6 patients were positive. Four were obtained post
      endoscopy and the remaining 2 before colonoscopy but the corresponding post
      endoscopy samples were negative. All organisms recovered were normal skin flora.
      All patients, including those with positive cultures, remained asymptomatic
      during the 72 hours after the procedure. CONCLUSIONS: Our findings indicate that
      lower intestinal endoscopy does not induce bacteremia in cirrhotic patients with
      or without ascites in the absence of gastrointestinal bleeding and do not support
      the routine use of prophylactic antibiotics in these patients.

PMID- 9925702
TI  - Endosonographic, endoscopic, and histologic evaluation of alterations in the
      rectal venous system in patients with portal hypertension.
AB  - BACKGROUND: Colorectal varices and congestive rectopathy or colopathy have been
      erratically reported in patients with portal hypertension. The clinical
      importance of these entities has not been described. We assessed the changes in
      the venous system of the rectum by endoscopy and rectal endosonography (EUS). We
      also assessed the role of factors such as etiology of portal hypertension, grade
      of esophageal varices, sclerotherapy, and liver disease severity on the
      occurrence of these vascular changes. METHODS: We studied changes in the venous
      system of the rectum using endoscopy and EUS in 60 patients with portal
      hypertension (cirrhotic 41, noncirrhotic 19). Ten patients with irritable bowel
      syndrome and 6 patients with hemorrhoids served as controls. Rectal varices were
      classified as tortuous, nodular, and tumorous. Corresponding appearances on
      rectal EUS were classified as single or discrete multiple, multiple, and
      innumerable submucosal veins, respectively. Evidence of congestive rectopathy was
      also recorded. RESULTS: Prevalence of rectal varices was 43.3% on endoscopy (73%
      tortuous, 19% nodular, and 8% tumorous) and 75% on EUS (p < 0.0005). The latter
      showed corresponding appearances of submucosal veins in 25 of 26 patients and
      detected submucosal veins not identified at endoscopy in 19 other patients.
      Congestive rectopathy was found in 38.3% of patients. Multiple small dilated
      vessels in the submucosa were seen in 23.3% patients on rectal EUS. The
      development of these vascular changes was significantly influenced by
      sclerotherapy, but not by higher grade of esophageal varices, the etiology of
      portal hypertension, or severity of liver disease. CONCLUSIONS: Changes in the
      rectal venous system are common, with rectal EUS being superior to endoscopy in
      detecting early, as well as florid, changes.

PMID- 9925703
TI  - Acute lower intestinal bleeding. Part II: etiology, therapy, and outcomes.

PMID- 9925704
TI  - Behcet's colitis.

PMID- 9925705
TI  - Endoscopic nasobiliary drain placement facilitates subsequent percutaneous
      transhepatic cholangiography.
AB  - BACKGROUND: Percutaneous biliary drainage is an established alternative to ERCP
      for managing bile duct obstruction. Although generally safe and effective,
      percutaneous drainage has its risks and is technically more difficult in patients
      with nondilated bile ducts. We report the use of nasobiliary drains and
      subsequent nasobiliary drain cholangiography to facilitate percutaneous biliary
      drainage by providing a target for accessing intrahepatic bile ducts.
      METHODS/RESULTS: Nine patients who were identified as requiring percutaneous
      biliary drainage underwent nasobiliary tube placement at completion of ERCP. Five
      of 9 patients had generalized intrahepatic ductal dilatation; in 4 patients,
      dilatation was focal or absent. Following nasobiliary drain cholangiography,
      percutaneous needle puncture of a bile duct was successful in all patients, in
      most cases with only a single puncture of the liver capsule. No procedural
      complications were encountered. CONCLUSION: Nasobiliary drain placement with
      subsequent nasobiliary drain cholangiography facilitates percutaneous biliary
      drainage and may be especially helpful in patients with nondilated intrahepatic
      bile ducts.

PMID- 9925706
TI  - A novel approach to ring-type foreign body removal: the "U-wire".
AB  - BACKGROUND: Foreign body ingestions are common, especially in pediatric,
      edentulous, psychiatric, and incarcerated populations. For the 20% of foreign
      bodies that do not pass spontaneously through the gastrointestinal tract, removal
      using modern, flexible endoscopes has become routine. METHODS: We describe the
      successful endoscopic removal of a ring-type or "closed loop" foreign body by
      means of a novel technique. Utilizing a nasogastric tube inserted alongside the
      endoscope, a guidewire inserted through the tube is directed through the ring
      with a "rat-tooth" grasping forceps passed through the accessory channel of the
      endoscope. The wire is snared and pulled up through the endoscope creating a "U,"
      with both ends of the wire outside of the patient. The nasogastric tube,
      endoscope, and foreign body may then be removed safely. RESULTS: The technique
      was easy to perform and the foreign body was removed without complication.
      CONCLUSIONS: Using the U-wire technique, ring-type foreign bodies may be readily
      and safely removed.

PMID- 9925707
TI  - A case of protein-losing gastropathy caused by acute Helicobacter pylori
      infection.

PMID- 9925708
TI  - Successful endoscopic therapy of cholangitis associated with intrahepatic
      cholangiectasis in adult cystic fibrosis.

PMID- 9925709
TI  - Hemobilia caused by a pseudoaneurysm of the hepatic artery diagnosed by EUS.

PMID- 9925710
TI  - Successful management of ruptured duodenal varices by means of endoscopic
      variceal ligation: report of a case.

PMID- 9925711
TI  - Multiple pyogenic granulomas in sigmoid colon.

PMID- 9925712
TI  - Solution to the dilemma of retrieving an endoscope from the esophagus.

PMID- 9925713
TI  - Screening flexible sigmoidoscopy by nonphysician endoscopists: it's here to stay,
      but is it the right test to do?

PMID- 9925714
TI  - Pediatric gastrointestinal endoscopy in malaysia 

PMID- 9925715
TI  - Comment 

PMID- 9925716
TI  - Improved method to inject contrast material during ERCP while using a triple
      lumen papillotome and guidewire.

PMID- 9925717
TI  - The Soehendra stent retriever.

PMID- 9925718
TI  - Selective basket insertion into the left intrahepatic duct.

PMID- 9925719
TI  - Botox injection for achalasia: a modified technique.

PMID- 9925720
TI  - Endoscopic sphincterotomy could have been a better alternative.

PMID- 9925721
TI  - Response 

PMID- 9925722
TI  - Pharmacological treatment of obesity: therapeutic strategies.

PMID- 9925723
TI  - 5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon-
      amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor
      antagonist.

PMID- 9925724
TI  - Bis- and mixed-tetrahydroisoquinolinium chlorofumarates: new ultra-short-acting
      nondepolarizing neuromuscular blockers.

PMID- 9925725
TI  - Discovery of a potent, orally active, nonsteroidal androgen receptor agonist: 4
      ethyl-1,2,3,4-tetrahydro-6- (trifluoromethyl)-8-pyridono[5,6-g]- quinoline
      (LG121071).

PMID- 9925726
TI  - Antagonists of the platelet P2T receptor: a novel approach to antithrombotic
      therapy.
AB  - The platelet P2T receptor plays a major role in platelet aggregation, and its
      antagonists are predicted to have significant therapeutic potential as
      antithrombotic agents. We have explored analogues of adenosine triphosphate
      (ATP), which is a weak, nonselective but competitive P2T receptor antagonist.
      Modification of the polyphosphate side chain to prevent breakdown to the agonist
      adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance
      affinity and selectivity for the P2T receptor led to the identification of 10e
      (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human
      platelets. Compound 10e was the first very potent antagonist of the P2T receptor,
      with a selectivity for that subtype of the P2 receptor family of >1000-fold.
      Further modification of the structure produced compound 10l (AR-C69931MX) having
      an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is
      little prolongation of bleeding time (1.4-fold), which is in marked contrast to
      the 5-6-fold found with GPIIb/IIIa antagonists.

PMID- 9925727
TI  - Mechanism-based competitive inhibitors of glyoxalase I: intracellular delivery,
      in vitro antitumor activities, and stabilities in human serum and mouse serum.
AB  - S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives (GSC(O)N(OH)C6H4X, where GS
      = glutathionyl and X = H (1), Cl (2), Br (3)) have been proposed as possible
      anticancer agents, because of their ability to strongly inhibit the methylglyoxal
      detoxifying enzyme glyoxalase I. In order to test this hypothesis, the in vitro
      antitumor activities of these compounds and their [glycyl,glutamyl] diethyl ester
      prodrug forms (1(Et)2-3(Et)2) have been examined. All three diethyl esters
      inhibit the growth of L1210 murine leukemia and B16 melanotic melanoma in
      culture, with GI50 values in the micromolar concentration range. Cell
      permeability studies with L1210 cells indicate that growth inhibition is
      associated with rapid diffusion of the diethyl esters into the cells, followed by
      enzymatic hydrolysis of the ethyl ester functions to give the inhibitory diacids.
      In contrast, the corresponding diacids neither readily diffuse into nor
      significantly inhibit the growth of these cells. Consistent with the hypothesis
      that cell growth inhibition is due to competitive inhibition of glyoxalase I,
      preincubation of L1210 cells with 2(Et)2 increases the sensitivity of these cells
      to the inhibitory effects of exogenous methylglyoxal. Compound 2(Et)2 is much
      less toxic to nonproliferating murine splenic lymphocytes, possibly reflecting
      reduced sensitivity to methylglyoxal and/or reduced chemical stability of the
      diacid inside these cells. Finally, a plasma esterase-deficient murine model has
      been identified that should allow in vivo testing of the diethyl esters.

PMID- 9925728
TI  - New bicyclam-AZT conjugates: design, synthesis, anti-HIV evaluation, and their
      interaction with CXCR-4 coreceptor.
AB  - We report the synthesis of mono- and bis-tetraazamacrocycle-AZT conjugates. All
      new compounds were screened for their ability to inhibit HIV-1 replication in MT4
      cell line and were compared to AZT alone. It appears that N-protected covalent
      prodrugs are equipotent to AZT as inhibitor of HIV replication, while N
      deprotected analogues exhibit both higher activity and selectivity against HIV
      infected cells. The most active antiviral compounds 27, 28, 34, and 35 were then
      tested for their binding capability to CXCR-4 receptor. N-Boc analogues 27 and 34
      were only weakly effective; in contrast, N-deprotected conjugates 28 and 35 were
      antagonists to 12G5 mAb binding until 0.05 and 5 microg/mL, respectively. The
      stability of compound 28 in human plasma was evaluated, and half-life was found
      to be approximately 8 h in the described conditions. All these results seem to
      demonstrate the confidence of our prodrug approach, with analogue 28 emerging as
      the best candidate as lead compound in HIV-1 polytherapy perspective.

PMID- 9925729
TI  - Domain-structured N1,N2-derivatized hydrazines as inhibitors of ribonucleoside
      diphosphate reductase: redox-cycling considerations.
AB  - Eight analogues of 1-[5-halogenosalicylidene]-2-[2'-pyridinoyl]hydrazine and -[2'
      pyridyl]hydrazine, four of 1-[pyridoxylidene]-2-[2'-pyridinoyl]hydrazine, seven
      of 1-[pyridoxylidene]-2-[2'-pyridyl]hydrazine, and one each of 1, 2
      bis[pyridoxylidene]diaminoethane and bis[pyridoxylidenehydrazino]phthalazine were
      synthesized. Their solutions in DMF were assayed for activity against the
      metalloenzyme ribonucleoside diphosphate reductase (RdR), prepared from a
      subcutaneously growing murine tumor (sarcoma 180) implanted in B6D2F3 male mice.
      The 14C-labeled CDP reductase was assayed by the modified method of Takeda and
      Weber, in which [14C]cytidine was separated from deoxycytidine by thin-layer
      chromatography (TLC) on cellulose foil. Distribution of radioactivity was
      assessed with an automatic TLC linear analyzer. Of the 31 compounds tested, 13
      were essentially inactive, 7 were highly active against RdR, and the remaining 20
      were slightly more active than hydroxyurea (used as a reference compound). The
      mechanism of inhibition is discussed in terms of three alternative pathways,
      initiated by sequestration of iron embedded in the R1 subunit of the
      metalloenzyme to form a C-centered chelate radical (via redox cycling).
      Alternatively, the latter could either reduce the tyrosyl radical or intercept
      radicals generated in the reduction process.

PMID- 9925730
TI  - Three-dimensional quantitative structure-activity relationship study on cyclic
      urea derivatives as HIV-1 protease inhibitors: application of comparative
      molecular field analysis.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      have been developed using comparative molecular field analysis (CoMFA) on a large
      data set (118 compounds) of diverse cyclic urea derivatives as protease
      inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal
      structures of HIV-1 protease bound with this class of inhibitors were used to
      derive the most probable bioactive conformations of the inhibitors. The enzyme
      active site was used as a constraint to limit the number of possible
      conformations that are sterically accessible. The test sets have been created
      keeping in mind structural diversity as well as the uniform simple statistical
      criteria (mean, standard deviation, high and low values) of the protease
      inhibitory activities of the molecules compared to the training sets. Multiple
      predictive models have been developed with the training sets (93 compounds in
      each set) and validated with the corresponding test sets (25 compounds in each
      set). All the models yielded high predictive correlation coefficients (q2 from
      0.699 to 0.727), substantially high fitted correlation coefficients (r2 from
      0.965 to 0.973), and reasonably low standard errors of estimates (S from 0. 239
      to 0.265). The steric and electrostatic effects have approximately equal
      contributions, 45% and 55% (approximately), respectively, toward explaining
      protease inhibitory activities. This analysis yielded models with significant
      information on steric and electrostatic interactions clearly discerned by the
      respective coefficient contour plots when overlapped on the X-ray structure of
      the HIV-1 protease. The HINT CoMFA study revealed significant contribution of
      hydrophobicity toward protease inhibitory activity. The 3D visualization
      technique utilizing these contour plots as well as the receptor site geometry may
      significantly improve our understanding of the inhibitor-protease (HIV-1)
      interactions and help in designing compounds with improved activity.

PMID- 9925731
TI  - Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor
      antibiotics radicicol and geldanamycin.
AB  - The cellular activity of several regulatory and signal transduction proteins,
      which depend on the Hsp90 molecular chaperone for folding, is markedly decreased
      by geldanamycin and by radicicol (monorden). We now show that these unrelated
      compounds both bind to the N-terminal ATP/ADP-binding domain of Hsp90, with
      radicicol displaying nanomolar affinity, and both inhibit the inherent ATPase
      activity of Hsp90 which is essential for its function in vivo. Crystal structure
      determinations of Hsp90 N-terminal domain complexes with geldanamycin and
      radicicol identify key aspects of their nucleotide mimicry and suggest a rational
      basis for the design of novel antichaperone drugs.

PMID- 9925732
TI  - Novel esters and amides of nonsteroidal antiinflammatory carboxylic acids as
      antioxidants and antiproliferative agents.
AB  - A series of phenolic antioxidant ester and amide derivatives of the nonsteroidal
      antiinflammatory drug naproxen was designed to have both antiinflammatory and
      cytoprotective activity. Compounds were evaluated in vitro both for antioxidant
      activity, as assessed indirectly by thiobarbituric acid reactive substance
      (TBARS) formation in a membrane lipid peroxidation assay, and for
      antiproliferative activity, as indexed by the inhibition of DNA synthesis in
      cultured human vascular endothelial cells. Compounds of this series exhibited
      potent antioxidant activity, with IC50 values (1.6-11.63 microM) 2-6-fold lower
      than that of Trolox (6-hydroxy-2,5, 7,8-tetramethylchroman-2-carboxylic acid) and
      400-1300-fold lower than that of vitamin E. Structural modifications of the ester
      or amide substructure (5a and 6a) did not affect antioxidant activity, but
      methylation of the 6-hydroxy substituent resulted in compound 6f which was devoid
      of antioxidant activity. Although indistinguishable in antioxidant activity, the
      amide derivatives tended to be more potent as antiproliferative agents than the
      corresponding esters. The IC50's for the amide derivatives (3, 5a-e, 8) ranged
      from 2 to 7 microM, while the IC50's for the structurally related esters (1, 2a
      c, 6a-e) ranged from 9 to 22 microM. Moreover, studies with compound 6a indicate
      that the observed inhibition of DNA synthesis is reversible, suggesting that the
      antiproliferative activity is due to a cytostatic rather than cytotoxic activity
      of the compounds. Thus, the antioxidant-naproxen derivatives represent a novel
      series of agents that both protect against free-radical damage and possess
      cytostatic activity in vascular endothelial cells. Studies are in progress to
      assess the utility of these compounds as potential components of an ocular
      irrigating solution.

PMID- 9925733
TI  - Structure-immunosuppressive activity relationships of new analogues of 15
      deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety.
AB  - A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent
      currently commercialized in Japan, was synthesized and tested in a graft-versus
      host disease (GVHD) model in mice. Using the general concept of bioisosteric
      replacement, variations of the hydroxyglycine central "C" region were made in
      order to determine its optimum structure in terms of in vivo immunosuppressive
      activity. By this way, the malonic derivative 13a was discovered as the first
      example of a new series of potent immunosuppressive agents encompassing a retro
      amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships
      of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation
      of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a
      which proved to be equally active as DSG in our GVHD model. Finally 27a was found
      to be the most potent derivative, being slightly more active than DSG in a heart
      allotransplantation model in rats. Due to the absence of chiral center in its
      structure and to its improved chemical stability compared to DSG, 27a was
      selected as a candidate for clinical evaluation.

PMID- 9925734
TI  - Ab initio conformational study of the phenylisoserine side chain of paclitaxel.
AB  - Paclitaxel (Taxol) and related compounds are important antitumor drugs, currently
      used for the treatment of several types of cancer. The flexible amino acidic C13
      side chain is a key element of the taxoid pharmacophore, and the identification
      of the bioactive conformation is a top priority for a better understanding of the
      mode of action of these anticancer agents. The conformational features of the
      side chain have been investigated by Hartree-Fock ab initio and semiempirical PM3
      calculations. To gain a better understanding of solvent effects, different
      molecular models of paclitaxel were used in the calculations. The gas-phase
      calculations confirm that only one conformation, named ch1 (very similar to the
      one found in the crystal structure of docetaxel), is present in apolar
      environments. The preference for this conformer has been rationalized in terms of
      its L shape, which minimizes steric and Coulombic interactions, and of a
      favorable arrangement of the glycolate moiety. When a polar solvent was simulated
      by different methods, a greater conformational variability was found, with
      different conformations differing by less than 1.5 kcal/mol. Among these
      conformations, only one (ch5', similar to molecule B of the crystal structure of
      paclitaxel) is particularly apt to interact with solvent molecules. In light of
      these data, it seems reasonable to assume that, when the drug is bound to the
      lipophilic pocket of the tubuline receptor, the C13 amino acidic side chain
      assumes a conformation close to ch1.

PMID- 9925735
TI  - Orally active, hydrolytically stable, semisynthetic, antimalarial trioxanes in
      the artemisinin family.
AB  - In only three chemical operations, natural trioxane lactone artemisinin (1) was
      converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds
      4-9. The three steps involved lactone reduction, replacement of the anomeric
      lactol OH by F using diethylaminosulfur trifluoride, and finally boron
      trifluoride-promoted substitution of F by aryl, heteroaryl, and acetylide
      nucleophiles. All of these C-10 nonacetal, chemically robust, enantiomerically
      pure compounds 4-9 have high antimalarial potencies in vitro against Plasmodium
      falciparum malaria parasites, and furans 5a and 5b and pyrrole 7a are
      antimalarially potent also in vivo even when administered to rodents orally.

PMID- 9925736
TI  - Vasopeptidase inhibitors: incorporation of geminal and spirocyclic substituted
      azepinones in mercaptoacyl dipeptides.
AB  - A series of 7-(di)alkyl and spirocyclic substituted azepinones were generated and
      incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl
      dipeptides. Clear structure-activity relationships with respect to both
      angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity in
      vitro were observed. The best in this series, compound 1g, a geminally
      dimethylated C-7-substituted azepinone, demonstrated excellent blood pressure
      lowering in animal models. Compound 1g (BMS-189921) is characterized by a good
      duration of activity and excellent oral efficacy in models relevant to ACE or NEP
      inhibition, and its activity is comparable to that of the clinically efficacious
      agent omapatrilat. Consequently this inhibitor has been advanced clinically for
      the treatment of hypertension and congestive heart failure.

PMID- 9925738
TI  - Synthesis and evaluation of 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)- 6
      fluoropurine mono- and diesters as potential prodrugs of ganciclovir.
AB  - A series of 2-amino-9-(1,3-dihydroxy-2-propoxymethyl)-6-fluoropurine mono- and
      diesters, 6a-h, were synthesized as potential prodrugs of ganciclovir and
      evaluated for their oral ganciclovir bioavailability in rats. Treatment of 2
      amino-6-chloro-9-(1, 3-dihydroxy-2-propoxymethyl)purine (4) with Me3N in DMF/THF
      (1/4) followed by the reaction of the resulting trimethylammonium chloride salt 5
      with KF in DMF gave 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)-6-fluoropurine (2)
      in 83% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O,
      (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) (6 equiv for 6a-d or 1 equiv for 6e-h) in
      DMF in the presence of a catalytic amount of DMAP produced the diesters 6a-d in
      92-98% yields and the monoesters 6e-h in 37-44% yields. Of the prodrugs tested in
      rats, the monoisobutyrate 6h achieved the highest ganciclovir bioavailability
      (45%) that is 15-fold higher than that from ganciclovir (3%), followed in order
      by the diisobutyrate 6d (42%), the diacetate 6a (41%), the monobutyrate 6g (41%),
      the monopropionate 6f (39%), the dipropionate 6b (35%), the dibutyrate 6c (35%),
      and the monoacetate 6e (29%). The prodrugs 6e-h were found to be quite stable at
      pH 6.0 (t1/2 = >29 days), 7.4 (t1/2 = >7 days), and 8.0 (t1/2 = >2 days) but had
      relatively short half-lives at pH 1.2 (t1/2 = 60-83 min).

PMID- 9925737
TI  - N-[2,2-dimethyl-3-(N-(4-cyanobenzoyl)amino)nonanoyl]-L-phenylalanine ethyl ester
      as a stable ester-type inhibitor of chymotrypsin-like serine proteases:
      structural requirements for potent inhibition of alpha-chymotrypsin.
AB  - We introduce a new potent inhibitor, N-[2, 2-dimethyl-3-(N-(4
      cyanobenzoyl)amino)nonanoyl]-L-phenylalanine ethyl ester (3), which
      preferentially inhibits serine proteases belonging to a chymotrypsin superfamily.
      This inhibitor, despite consisting of a stable ethyl ester structure, showed
      strong inhibitory activities toward bovine alpha-chymotrypsin, human cathepsin G,
      and porcine elastase by acting as an acylating agent. The calculated inactivation
      rate constant (kinact) and enzyme-inhibitor dissociation constant (Ki) against
      alpha-chymotrypsin were 0.0028 s-1 and 0.0045 microM, respectively (kinact/Ki =
      630 000 M-1 s-1). These kinetic parameters indicate that this inhibitor is one of
      the most powerful alpha-chymotrypsin inactivators ever reported. On the basis of
      structure-activity relationship (SAR) and structure-stability relationship
      studies of analogues of 3, which were modified in three parts of the molecule,
      i.e., the 4-cyanophenyl group, beta-substituent at the beta-amino acid residue,
      and ester structure, we suggest that the potent inhibitory activity of 3 is due
      to the following structural features: (1) the ethyl ester which enforces specific
      acyl-enzyme formation, (2) the n-hexyl group at the beta-position and 4
      cyanophenyl group which stabilize the acyl-enzyme, and (3) the phenylalanine
      residue which functions for the specific recognition of S1 site in the enzyme. In
      particular, the action of 3 as a potent inhibitor, but poor substrate, can be
      ascribed largely to the very slow deacylation rate depending on the structure
      factors cited in feature 2. The results of inhibition by 3 and its analogues
      against different serine proteases such as chymase, cathepsin G, and elastase
      suggest that these compounds recognize common parts in the active sites among
      these chymotrypsin-like serine proteases, and 3 is one of the most suitable
      structures to recognize those common parts. Our results provide an intriguing
      basis for further developments in the design of a stable ester-based selective
      serine protease inhibitor.

PMID- 9925739
TI  - 2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues
      of gamma-aminobutyric acid.
AB  - 3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2, 6-difluorophenol
      (7) were synthesized in eight and four steps, respectively, starting from 2,6
      difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as
      a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential
      bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and
      inhibition studies were carried out with pig brain gamma-aminobutyric acid
      aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme,
      indicating that the 2, 6-difluorophenol moiety appears to be able to substitute
      for a carboxylic acid to increase the lipophilicity of drug candidates.

PMID- 9925740
TI  - Mammalian centromeres: DNA sequence, protein composition, and role in cell cycle
      progression.
AB  - The centromere is a specialized region of the eukaryotic chromosome that is
      responsible for directing chromosome movements in mitosis and for coordinating
      the progression of mitotic events at the crucial transition between metaphase and
      anaphase. In this review, we will focus on recent advances in the understanding
      of centromere composition at the protein and DNA level and of the role of
      centromeres in sister-chromatid cohesion and mitotic checkpoint control.

PMID- 9925741
TI  - Role of microtubules in the organization of the Golgi complex.
AB  - The Golgi complex of mammalian cells is composed of cisternal stacks that
      function in processing and sorting of membrane and luminal proteins during
      transport from the site of synthesis in the endoplasmic reticulum to lysosomes,
      secretory vacuoles, and the cell surface. Even though exceptions are found, the
      Golgi stacks are usually arranged as an interconnected network in the region
      around the centrosome, the major organizing center for cytoplasmic microtubules.
      A close relation thus exists between Golgi elements and microtubules (especially
      the stable subpopulation enriched in detyrosinated and acetylated tubulin). After
      drug-induced disruption of microtubules, the Golgi stacks are disconnected from
      each other, partly broken up, dispersed in the cytoplasm, and redistributed to
      endoplasmic reticulum exit sites. Despite this, intracellular protein traffic is
      only moderately disturbed. Following removal of the drugs, scattered Golgi
      elements move along reassembling microtubules back to the centrosomal region and
      reunite into a continuous system. The microtubule-dependent motor proteins
      cytoplasmic dynein and kinesin bind to Golgi membranes and have been implicated
      in vesicular transport to and from the Golgi complex. Microinjection of dynein
      heavy chain antibodies causes dispersal of the Golgi complex, and the Golgi
      complex of cells lacking cytoplasmic dynein is likewise spread throughout the
      cytoplasm. In a similar manner, kinesin antibodies have been found to inhibit
      Golgi-to-endoplasmic reticulum transport in brefeldin A-treated cells and
      scattering of Golgi elements along remaining microtubules in cells exposed to a
      low concentration of nocodazole. The molecular mechanisms in the interaction
      between microtubules and membranes are, however, incompletely understood. During
      mitosis, the Golgi complex is extensively reorganized in order to ensure an equal
      partitioning of this single-copy organelle between the daughter cells. Mitosis
      promoting factor, a complex of cdc2 kinase and cyclin B, is a key regulator of
      this and other events in the induction of cell division. Cytoplasmic microtubules
      depolymerize in prophase and as a result thereof, the Golgi stacks become
      smaller, disengage from each other, and take up a perinuclear distribution. The
      mitotic spindle is thereafter put together, aligns the chromosomes in the
      metaphase plate, and eventually pulls the sister chromatids apart in anaphase. In
      parallel, the Golgi stacks are broken down into clusters of vesicles and tubules
      and movement of protein along the exocytic and endocytic pathways is inhibited.
      Using a cell-free system, it has been established that the fragmentation of the
      Golgi stacks is due to a continued budding of transport vesicles and a
      concomitant inhibition of the fusion of the vesicles with their target membranes.
      In telophase and after cytokinesis, a Golgi complex made up of interconnected
      cisternal stacks is recreated in each daughter cell and intracellular protein
      traffic is resumed. This restoration of a normal interphase morphology and
      function is dependent on reassembly of a radiating array of cytoplasmic
      microtubules along which vesicles can be carried and on reactivation of the
      machinery for membrane fusion.

PMID- 9925742
TI  - Transcriptional regulation of the p21((WAF1/CIP1)) gene.

PMID- 9925743
TI  - Nitric oxide induction of neuronal endonuclease activity in programmed cell
      death.
AB  - Neuronal survival is intricately linked to the maintenance of intact DNA. In
      contrast, neuronal degeneration following nitric oxide (NO) exposure is
      dependent, in part, on the degradation of DNA through programmed cell death
      (PCD). We therefore investigated in primary rat hippocampal neurons the role of
      endogenous deoxyribonucleases, enzymes responsible for metabolically derived DNA
      cleavage, during NO-induced neurodegeneration. Twenty-four hours following
      exposure to the NO generators sodium nitroprusside (300 microM) and SIN-1 (300
      microM), neuronal survival was reduced from approximately 88 to 23%. Treatment
      with aurintricarboxylic acid (1-100 microM), an endonuclease inhibitor, during NO
      exposure increased neuronal survival from 23 to 80% and decreased DNA
      fragmentation from 70 to 30% over a 24-h period. Enhancement of endonuclease
      activity alone with zinc chelation actively decreased neuronal survival from
      approximately 80% to approximately 34%. DNA digestion assays identified not only
      two constitutively active endonucleases, an acidic endonuclease (pH 4.0-7.0) and
      a calcium/magnesium-dependent endonuclease (pH 7.2-8.0), but also a NO-inducible
      magnesium-dependent endonuclease (pH 8.0). In the absence of endonuclease
      activity, DNA degradation did not occur during NO application, suggesting that
      endonuclease activity was a requisite pathway for NO-induced PCD. In addition, NO
      independently altered intracellular pH in ranges that were physiologically
      relevant for the activity of the endonucleases responsible for DNA degradation.
      Our identification and characterization of specific neuronal endonucleases
      suggest that the constitutive endonucleases may play a role in the initial stages
      of NO-induced PCD, but the subsequent "downstream" degradation of DNA may
      ultimately be dependent upon the NO-inducible endonuclease.

PMID- 9925744
TI  - Inhibition of caspases rescues brown adipocytes from apoptosis downregulating BCL
      XS and upregulating BCL-2 gene expression.
AB  - Serum deprivation of the immortalized brown adipocyte cell line resulted in
      growth arrest in G0/G1 phases of the cell cycle and apoptosis, as detected by DNA
      laddering, nuclei condensation and fragmentation, and an increase in the
      percentage of hypodiploid cells. In addition, apoptosis in these cells is
      accompanied by an induction of the expression of the apoptotic form of the Bcl-x
      gene, the isoform Bcl-xS, and by a decrease of Bcl-2 expression, Bcl-xL remaining
      almost undetectable. The loss of mitochondrial membrane potential was associated
      with apoptosis. Z-VAD, a cell-permeable inhibitor of caspases, but not
      cycloheximide, precludes DNA laddering under serum deprivation. Moreover, Z-VAD
      rescues serum-deprived brown adipocytes from apoptosis, decreasing the percentage
      of hypodiploid cells, the percentage of apoptotic cells under Tunnel assay, and
      the external display of phosphatidylserine. More importantly, Z-VAD survival
      effects on immortalized brown adipocytes concur with a downregulation of Bcl-xS
      mRNA/protein and an upregulation of Bcl-2 protein content. Ultimately, Z-VAD
      prevents the loss of mitochondrial membrane potential.

PMID- 9925745
TI  - Developmentally regulated expression of persyn, a member of the synuclein family,
      in skin.
AB  - Synucleins constitute a group of unique, evolutionarily conserved proteins that
      are expressed predominantly in neurons of the central and peripheral nervous
      system. Although the normal cellular functions of synucleins are not clear, these
      proteins have been implicated in various neurodegenerative conditions in humans.
      We found that persyn, a recently characterized member of the synuclein family, is
      expressed not only in the nervous system but also in the stratum granulosum of
      the epidermis of neonatal and adult mice. This finding together with our recent
      observations that persyn influences neurofilament network integrity in sensory
      neurons raises the possibility that persyn in skin could be involved in
      modulation of the keratin network.

PMID- 9925746
TI  - Reactivation of Delta-Notch signaling after injury: complementary expression
      patterns of ligand and receptor in dental pulp.
AB  - The evolutionarily conserved Notch-mediated intercellular signaling pathway is
      essential for proper embryonic development of many tissues and organs. Recent
      data suggest that Notch receptors and their membrane-bound ligands Delta and
      Serrate are involved in both patterning and cell fate determination during
      odontogenesis. It remains, however, uncertain if Notch signaling is important for
      tooth homeostasis and regeneration. Here we report on the expression of Notch
      receptors and the Delta1 ligand in dental pulp of normal and injured adult rat
      teeth. Notch receptors were absent from normal adult dental tissues, whereas
      expression was upregulated after injury. In injured teeth, Notch2 was expressed
      in mesenchymal cells of the pulp both close to the site of injury (i.e., in the
      dental crown) and at a distance from it (i.e., in the dental roots), Notch3
      expression was mainly associated with vascular structures, while Notch1
      expression was restricted to few pulpal cells close to the lesion. None of them
      was expressed in odontoblasts. Expression of Delta1 was upregulated in
      odontoblasts of the injured teeth, as well as in vascular structures. These
      results demonstrate the reactivation of the Notch signaling pathway during wound
      healing and, furthermore, highlight the similarity between developmental and
      regenerative processes.

PMID- 9925747
TI  - A wound-induced [Ca2+]i increase and its transcriptional activation of immediate
      early genes is important in the regulation of motility.
AB  - Upon mechanical wounding of a confluent quiescent monolayer, cells move into the
      denuded zone. However, it is not well known what signaling cascade connects
      release from contact inhibition to cell movement at the wound edge. Mechanical
      wounding induced an increase in the concentration of intracellular free Ca2+
      ([Ca2+]i) in endothelial cells at the wound edge. The [Ca2+]i signal was required
      for the transcriptional activation of two immediate early genes (IEGs), c-fos and
      c-jun, since blocking Ca2+ influx with Gd3+ or EGTA reduced IEG transcription,
      while augmenting Ca2+ influx increased IEG transcription. The transcriptional
      activation of the IEGs depended on protein kinase C and calmodulin-dependent
      protein kinase since treatment with the inhibitors Calphostin C and KN-62
      significantly reduced IEG expression. Briefly blocking Ca2+ influx also produced
      a long-term reduction of cell motility, while augmenting Ca2+ influx increased
      cell motility. To evaluate whether expression of IEGs might control cell
      movement, we microinjected sense or antisense cDNA to c-fos into cells after
      wounding. Antisense c-fos cDNA inhibited motility, while sense cDNA increased
      motility rates. These results suggested that the [Ca2+]i rise, induced by
      wounding, regulated the initiation of subsequent motility through the
      transcriptional activation of IEGs during wounding.

PMID- 9925748
TI  - Vasopressin stimulates the induction of heat shock protein 27 and alphaB
      crystallin via protein kinase C activation in vascular smooth muscle cells.
AB  - In the present study, we examined the effect of vasopressin on the induction of
      the low-molecular-weight heat shock proteins heat shock protein 27 (HSP27) and
      alphaB-crystallin in an aortic smooth muscle cell line, A10 cells. Vasopressin
      induced a time-dependent accumulation of HSP27 and alphaB-crystallin. The
      stimulatory effects of vasopressin were dose-dependent over the range 0.1 nmol/L
      to 0.1 micromol/L. The EC50 values for vasopressin were 2 (HSP27) and 4 nmol/L
      (alphaB-crystallin). Vasopressin induced increases in the levels of the mRNAs for
      HSP27 and alphaB-crystallin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a
      protein kinase C (PKC)-activating phorbol ester, induced an accumulation of HSP27
      (EC50, 20 nmol/L) and alphaB-crystallin (EC50, 2 nmol/L). In contrast, 4alpha
      phorbol 12,13-didecanoate, a non-PKC-activating phorbol ester, had no such
      effect. Staurosporine and calphostin C, inhibitors of PKC, significantly reduced
      the vasopressin-induced accumulation of HSP27 and alphaB-crystallin as well as
      that induced by TPA. BAPTA/AM and TMB-8, inhibitors of intracellular Ca2+
      mobilization, significantly reduced the vasopressin-induced accumulation of HSP27
      and alphaB-crystallin. These results strongly suggest that vasopressin stimulates
      the induction of HSP27 and alphaB-crystallin via PKC activation in vascular
      smooth muscle cells and that this effect of vasopressin is dependent on
      intracellular Ca2+ mobilization.

PMID- 9925750
TI  - Protein kinase calpha is an effector of hexamethylene bisacetamide-induced
      differentiation of Friend erythroleukemia cells.
AB  - The program of biochemical and molecular events necessary for commitment to
      erythroid cell differentiation is particularly well characterized in murine
      Friend erythroleukemia cell lines. Commitment to hemoglobin synthesis in response
      to a variety of chemical inducers, including hexamethylene bisacetamide and
      dimethyl sulfoxide is completed by 24 h and proceeds to terminal differentiation
      by 96 h. Phorbol 12-myristate 13-acetate, a classical tumor promoter phorbol
      ester that binds to protein kinase C, blocks differentiation in a reversible
      manner, suggesting an important role for protein kinase C signaling pathways. The
      classical protein kinase C isoforms alpha, betaI, and betaII, play distinct roles
      in the transduction of proliferative and differentiative signals in human, as
      well as in murine, erythroleukemia cells. Protein kinase Calpha has been
      implicated in differentiation of human erythroleukemia cells although its
      translocation to the nucleus has not been observed. Taking advantage of the
      ability of phorbol 12-myristate 13-acetate to block differentiation in Friend
      erythroleukemia cells, we determined the localization of the predominant protein
      kinase C isoforms alpha and betaI during differentiation and in response to their
      blockade. The ability of phorbol myristate acetate to preferentially diminish
      protein kinase Calpha-protein localization to the nucleus by 24 h and thereby
      block differentiation induced by hexamethylene bisacetamide was paralleled by the
      ability of protein kinase Calpha antisense transfection to block differentiation.
      In addition, beta-globin transcription, assessed by polymerase chain reaction,
      was significantly decreased in protein kinase Calpha antisense-transfected cells
      compared to that seen in vector transfected ones. Taken together, these data
      suggest an important temporal role for nuclear protein kinase Calpha localization
      in Friend erythroleukemia cell differentiation.

PMID- 9925749
TI  - Cyclin D1 inhibits cell proliferation through binding to PCNA and cdk2.
AB  - Cyclin D1 is known as a promoting factor for cell growth. We previously showed,
      however, that the expression of cyclin D1 increases markedly in senescent human
      fibroblasts in vitro. Here we investigate whether the overexpression of cyclin D1
      inhibits cell proliferation. Colony formation after transfection with the cyclin
      D1 expression vector was repressed in NIH-3T3, TIG-1, CHO-K1, and HeLa cells,
      compared with those with mock and cyclin E expression vectors. A transient
      transfection assay demonstrated that the overexpression of cyclin D1 inhibited
      DNA synthesis of TIG-1 cells. The complexes of cyclin D1 with PCNA and cdk2
      increased remarkably in senescent cells, compared with young counterparts.
      Excessive glutathione S-transferase (GST)-cyclin D1 inhibited DNA replication and
      repressed cdk2-dependent kinase activity in vitro. DNA synthesis of NIH-3T3
      transfectants with PCNA or cdk2 expression vectors was not inhibited by the
      overexpression of cyclin D1. These results indicate that an excessive level of
      cyclin D1 represses cell proliferation by inhibiting DNA replication and cdk2
      activity through the binding of cyclin D1 to PCNA and cdk2, as it does in
      senescent cells.

PMID- 9925751
TI  - Cytoskeletal association of the A and B nucleoside diphosphate kinases of
      interphasic but not mitotic human carcinoma cell lines: specific nuclear
      localization of the B subunit.
AB  - The human A and B subunits of nucleoside diphosphate kinase (NDP kinase), encoded
      by the nm23-H1 and nm23-H2 genes, respectively, associate as homo- or
      heterohexamers to be catalytically active for the synthesis of nucleoside
      triphosphates. Despite 88% identity, they appear to possess specific functions.
      The nm23-H1 gene is implicated in tumor progression and metastasis, and the nm23
      H2 gene product is a transcription factor for c-myc. To determine if these
      distinct functions reflect different subcellular localizations, the distribution
      of the A and B NDP kinases was analyzed by immunocytofluorescence microscopy in
      human breast cancer cell lines (MCF-7 and MDA-MB-231) using highly specific
      polyclonal and monoclonal antibodies. Interphasic cells exhibited a granular and
      filamentous cytoplasmic staining, particularly intense around nuclei, with both
      anti-NDP kinase A and B antibodies. The filamentous component observed with
      either anti-A or anti-B antibodies was altered in parallel to tubulin labeling
      with compounds interacting with microtubules, such as taxol and colchicine.
      Confirming published biochemical data, a partial colocalization with the vimentin
      network was observed in the MDA-231 cell line. A nuclear and nucleolar
      localization of NDP kinase B was shown by confocal microscopy which was not
      observed with the A enzyme. In dividing cells, NDP kinase labeling was punctiform
      and was not colocalized with the mitotic spindle. In conclusion, the A and B NDP
      kinases are similarly distributed in cytosol, associated partly to microtubules
      supporting a role in nucleotide channeling. Only the B enzyme is present in
      nuclei in accord with its role as a DNA binding protein. Their altered
      localization in dividing cells suggests colocalization with yet unidentified
      structures which are not intermediate filament aggregates.

PMID- 9925752
TI  - Lymphatic endothelial tumors induced by intraperitoneal injection of incomplete
      Freund's adjuvant.
AB  - Endothelial cells form the inner lining of blood and lymphatic vessels. In mice,
      only tumors of the blood vessel endothelium (haemangiomas) have been thus far
      reported. Here we describe a highly reproducible method for the induction of
      benign tumors of the lymphatic endothelial cells (lymphangiomas) in mice by
      intraperitoneal injection of incomplete Freund's adjuvant. Morphological and
      histopathological studies of the lesions revealed the presence of cells at
      various levels of vascular development. The lymphangiomas developed in the
      peritoneal cavity and expressed the endothelial markers CD31/PECAM (platelet
      endothelial cell adhesion molecule), CD54/ICAM-1 (InterCellular Adhesion Molecule
      1), and CD102/ICAM-2, as well as the vascular endothelial growth factor (VEGF)
      receptor Flk-1, the endothelial cell specific receptors Tie-1 and Tie-2 and the
      lymphatic endothelial cell specific Flt4 receptor as shown by in situ
      hybridization. The Flk-1 and Flt4 receptors were also identified in immunoblots
      of the tumors and in cells cultured from them. When induced in beta-galactosidase
      knock-in Flt4(+/-) mice, the tumor endothelia could be stained blue in a number
      of tumor cells although the staining was of lower intensity than in normal
      lymphatic vessels. The tumor-derived cells could be propagated in vitro and they
      spontaneously differentiated, forming vessel-like structures. Murine
      lymphangiomas thus represent a highly reproducible and convenient source of
      lymphatic endothelial cells.

PMID- 9925753
TI  - Induction of apoptosis due to lowering the level of eukaryotic initiation factor
      2-associated protein, p67, from mammalian cells by antisense approach.
AB  - p67, a cellular glycoprotein, protects eIF2alpha from phosphorylation by
      inhibitory kinases such as double-stranded RNA dependent eIF2 kinase, PKR, and
      heme-controlled repressor and thus promotes protein synthesis in mammalian cells.
      To investigate whether p67 is essential for the survival of mammalian cells, the
      basal level of p67 was lowered from rat tumor hepatoma cells using antisense
      approach. The antisense p67 RNA specifically lowered the levels of p67 message
      and the protein from these cells. As a result, the level of eIF2alpha
      phosphorylation increased significantly, the overall rate of protein synthesis
      decreased, and the rate of DNA synthesis also decreased in mammalian cells with
      low levels of p67 as compared to that seen in control cells. In addition, the
      majority of the cells with low levels of p67 are arrested at the G1 phase of the
      cell cycle and die with apoptosis. Taken together, these results suggest that
      appropriate levels of p67 is required for normal growth of mammalian cells.

PMID- 9925754
TI  - Fanconi anemia C protein acts at a switch between apoptosis and necrosis in
      mitomycin C-induced cell death.
AB  - Deregulation of apoptosis seems to be a hallmark of the Fanconi anemia (FA)
      syndrome. In order to further define the role of the FA protein from
      complementation group C (FAC) in apoptosis, we characterized parameters modified
      during the mitomycin-C (MMC)-induced apoptotic program. It is shown that despite
      a higher level of cell death for FA compared to normal lymphoblasts after MMC
      treatment, FA cells do not display a marked DNA fragmentation. Furthermore, while
      playing a central role in MMC apoptosis of normal lymphoblasts, the activity of
      caspase-3-like proteases is altered in FA cells. Interestingly, the disruption of
      the mitochondrial transmembrane potential (Deltapsi), an early event that can
      lead to apoptotic or to necrotic death, is accomplished similarly in FA and in
      normal cells. Finally, it is shown that the overexpressed FAC protein inhibited
      the apoptotic steps, with the exception of the decrease of the Deltapsi.
      Altogether, our results indicate that the FAC protein acts at a step preceding
      the activation of the caspases and after the modification of the Deltapsi, a
      decision point at which cells can be pushed toward either apoptosis or necrosis
      and which, consequently, regulates the balance between the two modes of cell
      death.

PMID- 9925755
TI  - Poly(ADP-ribose) glycohydrolase is present and active in mammalian cells as a 110
      kDa protein.
AB  - Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the
      catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal
      proteins. Purification of PARG from many tissues revealed heterogeneity in
      activity and structure of this enzyme. To investigate PARG structure and
      localization, we developed a highly sensitive one-dimensional zymogram allowing
      us to analyze PARG activity in crude extracts of Cos-7, Jurkat, HL-60, and Molt-3
      cells. In all extracts, a single PARG activity band corresponding to a protein of
      about 110 kDa was detected. This 110-kDa PARG activity was found mainly in
      cytoplasmic rather than in nuclear extracts of Cos-7 cells.

PMID- 9925757
TI  - Novel formula for cell kinetics in xenograft model of hepatocellular carcinoma
      using histologically calculable parameters.
AB  - The growth rate of tumors should be assessed in terms of both tumor cell
      proliferation and death. The former is considered to be determined by growth
      fraction and cell-cycle time, whereas the latter is mainly determined by
      apoptosis, especially in tumors with a low level of necrosis. While most
      hepatocellular carcinomas (HCCs) in a relatively early stage contain only a small
      amount of necrosis, the growth rate supposedly depends mainly on growth fraction,
      cell-cycle time, and apoptosis. However, their quantitative relationship remains
      unknown. We have derived a novel theoretical formula for determining this
      relationship in nonnecrotic HCC, using Ki-67-positive index, apoptotic score, and
      a correction factor, all calculable by histological assessment without injecting
      labeling agents. Furthermore, we confirmed the reliability of this formula, using
      a xenograft model of human HCC with less than 15% necrosis. In this model the
      values of cell-cycle time calculated from the formula were very close to those
      estimated by a conventional double-labeling method and showed high correlations.
      Since our novel formula can clarify the cell kinetics without cumbersome labeling
      procedures, it is expected to be clinically applicable to HCC with a small
      portion of necrosis, using the radiographically measured growth rate and the
      histologically assessed cell kinetic parameters.

PMID- 9925756
TI  - Molecular characterization of the hnRNP A2/B1 proteins: tissue-specific
      expression and novel isoforms.
AB  - hnRNP A2/B1 proteins are among the most abundant pre-mRNA-binding proteins of
      vertebrates and structurally similar to hnRNP A1. We have produced two specific
      monoclonal antibodies against A2 and B1 and studied their molecular
      characteristics and in vivo expression in rat tissues. Immunoprecipitation
      demonstrated that the hnRNP A2/B1 complexes contain many snRNP (small nuclear
      ribonucleoprotein) proteins, consistent with their role in pre-mRNA splicing. RNA
      polymerase II inhibition causes nucleocytoplasmic shuttling of A2 and B1. In most
      tissues, they are localized in the nucleus; however, in the squamous epithelium
      of the skin and esophagus A2 is also distributed in the cytoplasm. The relative
      amounts of A2 and B1 are not constant among different tissues. In the adrenal,
      only A2 is extremely abundant in the medulla but not in the cortex. In the testis
      the expression of A2 and B1 are observed through spermatogenesis, and different
      from A1 which is stringently repressed in spermatocytes. We also found and cloned
      a novel testis-specific isoform of A2/B1, namely hnRNP B0. The difference of
      expression of A2, B1, and A1 provides new information on their in vivo roles. The
      diversity of A/B group hnRNP proteins may have important effects on the
      posttranscriptional regulation of cell-specific gene expression.

PMID- 9925759
TI  - Potential m-calpain substrates during myoblast fusion.
AB  - Many studies have demonstrated that m-calpain was implicated in cell membrane
      reorganization-related phenomena during fusion via a regulation by calpastatin,
      the specific Ca2+-dependent proteolytic inhibitor. However, the real biological
      role of this protease is unclear because many targeted proteins are still
      unknown. Using different digestion experiments we have demonstrated that desmin,
      vimentin, talin, and fibronectin represent very good substrates for this
      proteinase capable of cleaving them in fragments which are immediately degraded
      by other enzymatic systems. Concerning intermediate filaments, we showed that
      during the phenomenon of fusion, the amount of desmin was significantly reduced
      while the concentration of vimentin presented a steady level. On the other hand,
      we have conducted biological assays on cultured myoblasts supplemented by
      exogenous factors such as calpain inhibitors or antisense oligonucleotides
      capable of stimulating or inhibiting m-calpain activity. The effect of such
      factors on fusion and concomitantly on the targeted substrates was analyzed and
      quantified. When m-calpain activity and myoblast fusion were prevented by
      addition of calpain inhibitors entering the cells, the amounts of desmin, talin,
      and fibronectin were increased, whereas the amount of vimentin was unchanged.
      Using antisense strategy, similar results were obtained. In addition, when the
      phenomenon of fusion was enhanced by preventing calpastatin synthesis, the
      amounts of desmin, talin, and fibronectin were significantly reduced. Taken
      together, these results support the hypothesis that m-calpain is involved in
      myoblast fusion by cleaving certain proteins identified here. This cleavage could
      modify membrane and cytoskeleton organization for the myoblasts to fuse.

PMID- 9925758
TI  - The muscle-specific laminin receptor alpha7 beta1 integrin negatively regulates
      alpha5 beta1 fibronectin receptor function.
AB  - alpha7 beta1 is the major integrin complex expressed in differentiated muscle
      cells where it functions as a laminin receptor. In this work we have expressed
      the alpha7 integrin subunit in CHO cells to investigate the functional properties
      of this receptor. After transfection with alpha7 CHO cells acquired the ability
      to adhere and spread on laminin 1 consistent with the laminin receptor activity
      of the alpha7 beta1. alpha7 transfectants, however, showed a 70% reduction in the
      ability to adhere to fibronectin and were unable to assemble a fibronectin
      matrix. The degree of reduction was inversely related to the level of alpha7
      expression. To define the mechanisms underlying this adhesive defect we analyzed
      surface expression and functional properties of the alpha5 beta1 fibronectin
      receptor. Although cell surface expression of alpha5 beta1 was reduced by a
      factor of 20-25% in alpha7 transfectants compared to control untransfected cells,
      this slight reduction was not sufficient to explain the dramatic reduction in
      cell adhesion (70%) and matrix assembly (close to 100%). Binding studies showed
      that the affinity of 125I-fibronectin for its surface receptor was decreased by
      50% in alpha7 transfectants, indicating that the alpha5 beta1 integrin is
      partially inactivated in these cells. Inactivation can be reversed by Mn2+, a
      cation known to increase integrin affinity for their ligands. In fact, incubation
      of cells with Mn2+ restored fibronectin binding affinity, adhesion to
      fibronectin, and assembly of fibronectin matrix in alpha7 transfectants. These
      data indicate that alpha7 expression leads to the functional down regulation of
      alpha5beta1 integrin by decreasing ligand binding affinity and surface
      expression. In conclusion, the data reported establish the existence of a
      negative cooperativity between alpha7 and alpha5 integrins that may be important
      in determining functional regulation of integrins during myogenic
      differentiation.

PMID- 9925760
TI  - The effects of superoxide and the peripheral benzodiazepine receptor ligands on
      the mitochondrial processing of manganese-dependent superoxide dismutase.
AB  - The mitochondrion imports and processes the vast majority of the proteins that
      constitute its structural elements and metabolic pathways. To study mitochondrial
      precursor processing in the context of the cellular environment, we employed the
      baculovirus expression system to overexpress the prototypical precursor protein,
      human manganese-dependent superoxide dismutase (hMn-SOD). It was found that
      superoxide produced by hyperoxic culture conditions (95% O2 atm) or the redox
      cycling agent paraquat caused a lesion of the import/processing of precursor hMn
      SOD in the baculovirus model. The oxidation of key sulfhydryl groups as a
      component of the mitochondrial processing lesion was implicated by the
      observation that the sulfhydryl reducing agent dithiothreitol was completely
      effective in preventing the block of hMn-SOD processing induced by paraquat.
      Interestingly, the peripheral benzodiazepine receptor (PBzR) agonists PK11194,
      Ro5-4864, and protoporphyrin IX were all found to enhance mitochondrial
      processing of the hMn-SOD precursor protein, suggesting a role for the PBzR in
      the regulation of mitochondrial import of proteins. Collectively, our results
      suggest a possible redox-regulated mechanism of mitochondrial protein import that
      may lead to less efficient precursor protein uptake by mitochondria under
      severely oxidizing conditions.

PMID- 9925761
TI  - Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct
      effect on cell nuclei.
AB  - A fraction from human milk containing spf-multimer alpha-lactalbumin (MAL)
      induces apoptosis in tumor cells and immature cells but spares mature cells. The
      mechanism of apoptosis induction and the molecular basis for the difference in
      susceptibility between tumor cells and healthy cells have not been defined. In
      this study we examined the interaction of MAL with different cellular
      compartments, using confocal microscopy and subcellular fractionation. MAL was
      shown to accumulate in the nuclei of sensitive cells rather than in the cytosol,
      the vesicular fraction, or the ER-Golgi complex. Nuclear uptake occurred rapidly
      in cells that were susceptible to the apoptosis-inducing effect, but not in
      nuclei of resistant cells. Nuclear uptake was through the nuclear pore complex
      and was critical for the induction of DNA fragmentation, since inhibition of
      nuclear uptake with WGA rescued digitonin-permeabilized cells from induction of
      DNA fragmentation. Ca2+ was required for MAL-induced DNA fragmentation but
      nuclear uptake of MAL was independent of Ca2+. This way MAL differs from most
      previously described agents in that it crosses the plasma membrane and cytosol,
      and enters cell nuclei where it induces DNA fragmentation through a direct effect
      at the nuclear level.

PMID- 9925762
TI  - Spatial organization of four hnRNP proteins in relation to sites of
      transcription, to nuclear speckles, and to each other in interphase nuclei and
      nuclear matrices of HeLa cells.
AB  - RNA polymerase II transcripts are complexed with heterogeneous nuclear
      ribonucleoprotein (hnRNP) proteins. These proteins are involved in several
      aspects of the maturation and transport of hnRNA. We performed a detailed study
      of the spatial distribution of four hnRNP proteins (hnRNP C, I, L, and U) in HeLa
      nuclei, using immunofluorescent labeling and confocal microscopy. Despite the
      fact that hnRNP proteins have been shown to coimmunoprecipitate, a hallmark of
      hnRNP proteins, we find that hnRNP C, I, and L have a spatial nuclear
      distribution that is not related to that of hnRNP U. We also examined the
      distribution of hnRNP proteins in relation to that of nascent transcripts. The
      four hnRNP proteins that we examined are not enriched at sites of RNA synthesis.
      Using antibodies against the nuclear poly(A)-binding protein (PAB II) we
      investigated the relationship between the distribution of hnRNP proteins and that
      of nuclear domains (nuclear speckles) that are enriched in splicing factors,
      poly(A)+RNA, and PAB II. We found that the four hnRNP proteins are not enriched
      in these domains. This indicates that the poly(A)+RNA, present in high
      concentration in speckles, is not complexed with these hnRNP proteins. This is in
      agreement with the notion that poly(A)+RNA in speckles is different from ordinary
      hnRNA. Previously, we have shown that hnRNP proteins are the major protein
      components of the fibrogranular internal nuclear matrix (K. A. Mattern et al.
      (1996) J. Cell. Biochem. 62, 275-289; K. A. Mattern et al. (1997) J. Cell.
      Biochem. 65, 42-52). We observed that in nuclear matrices the spatial
      distributions of the four hnRNP proteins, like that of nascent RNA and PAB II,
      are essentially the same as observed in intact nuclei. Moreover, also in nuclear
      matrix preparations, like in intact nuclei, nascent RNA and PAB II have spatial
      distributions that differ from those of hnRNP proteins. Our results are
      compatible with the notion that hnRNP proteins are able to form complexes of many
      different, probably overlapping, compositions.

PMID- 9925764
TI  - Transfection with different connexin genes alters growth and differentiation of
      human choriocarcinoma cells.
AB  - To examine the role of cell-cell communication via gap junctions in controlling
      proliferation and differentiation we transfected the malignant trophoblast cell
      line Jeg-3, which exhibits extremely low cell-cell communication mediated by
      endogenously expressed connexin40, with connexin26, connexin40, and connexin43,
      respectively. In vitro growth of all cell clones transfected with connexin genes
      was significantly reduced compared to controls. This effect corresponded to a
      significant increase in total junctional conductance of all clones. Single
      channel conductances for channels formed by the transfected connexins were in the
      range of the values published previously. Though total junctional conductance
      varied highly among clones and even within one clone, differentiation of the
      cells indicated by beta-hCG secretion was most prominent in the clones that
      revealed the largest amount of well-coupled cell pairs. Connexin26 channels
      enable cells of one clone to reduce drastically growth rate and produce
      significantly higher secretion of beta-hCG. Connexin43 had only moderate effects
      on the differentiation properties of Jeg-3 cells. These findings suggest that
      restoration of cell-cell communication plays a role in growth reduction and in
      differentiation of tumor cells and that different channel proteins might have
      different effects.

PMID- 9925763
TI  - Regulation of proliferation and apoptosis by epidermal growth factor and protein
      kinase C in human ovarian surface epithelial cells.
AB  - Epidermal growth factor (EGF) is produced in the ovary and influences
      proliferation of the malignant ovarian surface epithelium (OSE); yet its role in
      malignancy or in regulating the normal surface epithelium is unclear. In human
      OSE cells derived from primary cultures of normal tissue transfected with SV40
      large T antigen (IOSE cells), EGF promoted survival but not proliferation. This
      survival effect was reversed by acute treatment with the phorbol ester, 12-0
      tetradecanoyl-13-phorbol acetate (TPA) which alone markedly inhibited IOSE
      proliferation. We tested whether the activities of the mitogen-activated protein
      kinases (ERK1/2 and JNK1) varied in response to EGF, TPA, or combinations of
      these agonists and if the same treatments altered patterns of immediate early
      gene expression. Alone, EGF activated ERK1/2, increased and sustained levels of c
      jun mRNA, but had almost no effect on JNK1 activation. Conversely, PKC activation
      resulted in a rapid, but transient induction of c-fos RNA and of both kinases,
      JNK1 and ERK2. When combined, EGF and TPA further enhanced the phosphorylation of
      both enzymes despite inhibiting survival. Though JNKs and ERKs are thought to
      transduce opposing cellular responses, in IOSE cells, robust costimulation of the
      JNK and ERK pathways may redirect the survival message.

PMID- 9925765
TI  - Caspase-1 is not involved in CD95/Fas-induced apoptosis in Jurkat T cells.
AB  - It is now well established that the caspases, a family of cysteine proteases,
      play a key role in apoptosis. Although overexpressing each of the caspases in
      cells triggered apoptosis, the precise role and contribution of individual
      caspases are still unclear. Caspase-1, the first caspase discovered, was
      initially implicated in mammalian apoptosis because of its similarity to the gene
      product ced-3. Using whole cells as well as an in vitro system to study
      apoptosis, the role of caspase-1 in Fas-mediated apoptosis in Jurkat T cells was
      examined in greater detail. Using various peptide-based caspase inhibitors, our
      results showed that N-acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and
      benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone efficiently blocked Fas
      mediated apoptosis in Jurkat T cells, whereas N-acetyl-Tyr-Val-Ala-Asp aldehyde,
      which is more specific for caspase-1, had little effect. Cell lysates derived
      from anti-Fas-stimulated cells, which readily induced apoptotic nuclei morphology
      and DNA fragmentation in isolated thymocyte nuclei, had no caspase-1 activity
      using proIL-1beta as a substrate. Time-course studies showed no caspase-1
      activity during the activation of apoptosis in Jurkat cells by agonistic Fas
      antibodies. Furthermore, no pro-caspase-1 protein nor activated form of the
      protein was detected in normal or apoptotic Jurkat cells. In contrast, both
      caspase-2 and caspase-3 were readily detected as proenzymes in control cells and
      their activated forms were detected in apoptotic cells. Incubation of recombinant
      active caspase-1 with control cell lysates did not activate the apoptotic cascade
      as shown by the lack of detectable apoptotic nuclei promoting activity using
      isolated nuclei as substrate. However, under similar conditions proIL-1beta was
      readily processed into the mature cytokine, indicating that the recombinant
      caspase-1 remained active in the presence of control cell lysates. Taken together
      our results demonstrate that caspase-1 is not required for the induction of
      apoptosis in Jurkat T cells mediated by the Fas antigen.

PMID- 9925766
TI  - Demonstration of heterodimer formation between S100B and S100A6 in the yeast two
      hybrid system and human melanoma.
AB  - S100B (S100beta) and S100A6 (calcyclin) are two 10-kDa Ca2+- and Zn2+-binding
      proteins coexpressed in melanoma and cell-cycle regulated. These proteins are
      members of the S100 subfamily and are thought to exert their function through
      interaction with intracellular target proteins. In order to search for potential
      target proteins interacting with S100B, we used a yeast two-hybrid strategy with
      human S100B as bait to screen a human brain cDNA library. The fusion proteins
      interacting with the S100B bait were identified as S100B, S100A1, and S100A6.
      This indicates the potential of S100B to form homodimers and heterodimers with
      other members of the S100 subfamily. By Northern and Western blotting, S100B and
      S100A6 were shown to be expressed at high levels in a panel of human melanoma
      cell lines. S100B and S100A6 were coimmunoprecipitated from melanoma cell lysates
      in the presence of 100 microM Zn2+. Confocal microscopy demonstrated that both
      proteins were distributed throughout the cytoplasm and concentrated in the
      nucleus. The demonstration of an association and colocalization of S100B and
      S100A6 in melanoma supports the possibility that an S100B/S100A6 heterodimer
      plays a functional role in these cells.

PMID- 9925767
TI  - Caveolin-3 is associated with the T-tubules of mature skeletal muscle fibers.
AB  - Caveolae are abundant in skeletal muscle and their coat contains a specific
      isoform of caveolin, caveolin-3. It has been suggested that during muscle
      development, caveolin-3 is associated with the T-tubules, but that in adult
      muscle it is found on the plasma membrane only. We have studied the distribution
      of caveolin-3 in single skeletal muscle fibers from adult rat soleus by confocal
      immunofluorescence and by immunogold electron microscopy. We found that caveolin
      3 occurs at the highest density on the plasma membrane but is also present in the
      core of the fibers, at the I-band/A-band interface where it is associated with
      the T-tubules. In neither domain of the muscle surface does caveolin-3 colocalize
      with the glucose transporter GLUT4 and there is no evidence for internalization
      of the caveolae in muscle.

PMID- 9925768
TI  - The plant nucleoskeleton: ultrastructural organization and identification of NuMA
      homologues in the nuclear matrix and mitotic spindle of plant cells.
AB  - In the present work we investigate the structural organization of the
      nucleoskeleton of Allium cepa meristematic root cells. Resinless sections reveal
      for the first time a residual filamentous network in plant nuclei. This network
      is composed of branched knobbed filaments with associated globular structures,
      connected to the lamina and to the dense aggregates of different sizes. Results
      of immunoblotting show that many components of this network are homologues of
      intermediate filament-type proteins. NuMA, a coiled-coil protein related to
      intermediate filaments, found in animal cells, can also be detected in this plant
      nuclear matrix system. Immunofluorescence reveals a diffuse distribution of the
      animal NuMA homologues in plant nuclear core filaments in interphase. Resinless
      immunoelectron microscopy further reveals a distribution along the extended
      filaments and the dense aggregates. During mitosis, in contrast to the
      accumulation at the poles in animal cells, NuMA homologues in plant onion cells
      show a diffuse pattern, which may correspond to the spindle matrix. Our data are
      the first report of the conservation in plants of NuMA proteins, which may be
      involved in both nuclear and mitotic spindle organizations.

PMID- 9925770
TI  - Volume 242, number 1 (1998), in article no. EX984101, "DeltaF508 CFTR localizes
      in the endoplasmic reticulum-golgi intermediate compartment in cystic fibrosis
      Cells," by anne gilbert, michel jadot, ekaterina leontieva, simone wattiaux-De
      coninck, and robert wattiaux, pages 144-152 

PMID- 9925769
TI  - Chondrocyte apoptosis induced by aggrecan G1 domain as a result of decreased cell
      adhesion.
AB  - A major feature of cartilage deterioration during joint injury and disease is
      aggrecan degradation and the loss of proteoglycan. Most of the degraded fragments
      are released into the circulatory system except the G1 domain which accumulates
      locally in the synovial fluid and cartilage because of its hyaluronan-binding
      ability. In this study, our objective was to investigate the effects of G1
      accumulation on chondrocyte function. We chose to mimic the accumulation of G1
      domain by developing a method to express G1 in chondrocytes. We transiently and
      stably expressed aggrecan G1 domain in the cells and tested the effects of G1 in
      cell adhesion and apoptosis. Overexpression of the G1 construct induced apoptosis
      in adherent chondrocytes but not in chondrocytes maintained in suspension
      cultures. Higher levels of G1 expression caused greater reduction in cell
      substratum interaction and induced more cell death. The effect was dose
      dependent. To corroborate our findings, the role of G1 in reducing adhesion and
      inducing apoptosis was further investigated in fibroblasts. We found that low
      adherent cultures also had high levels of apoptosis. Our results suggest that G1
      induced apoptosis by destabilizing cell-substratum interaction.

PMID- 9925772
TI  - Volume 39, Number 3, (1997), in Article No. GE964520 "Two Novel Human Members of
      an Emerging Mammalian Gene Family Related to Mono-ADP-Ribosylating Bacterial
      Toxins," by Friedrich Koch-Nolte, Friedrich Haag, Rickmer Braren, Maren Kuhl, Jan
      Hoovers, Sriram Balasubramanian, Fernando Bazan, and Heinz-Gunter Thiele, pages
      370-376:

PMID- 9925771
TI  - Volume 242, number 1 (1998), in article no. EX984115, "Cdc2-independent induction
      of premature mitosis by okadaic acid in HeLa Cells," by S. Ghosh, N. Paweletz,
      and D. Schroeter, pages 1-9 

PMID- 9925773
TI  - Surface structures of native bacteriorhodopsin depend on the molecular packing
      arrangement in the membrane.
AB  - Bacteriorhodopsin is the one of the best-studied models of an ion pump. Five
      atomic models are now available, yet their comparison reveals differences of some
      loops connecting the seven transmembrane alpha-helices. In an attempt to resolve
      this enigma, topographs were recorded in aqueous solution with the atomic force
      microscope (AFM) to reveal the most native surface structure of bacteriorhodopsin
      molecules in the purple membrane. Individual peptide loops were observed with a
      lateral resolution of between 4.5 A and 5.8 A, and a vertical resolution of about
      1 A. The AFM images demonstrate for the first time, that the shape, the position,
      and the flexibility of individual polypeptide loops depend on the packing
      arrangement of bacteriorhodopsin molecules in the lipid bilayer.

PMID- 9925774
TI  - The prosequence of thermolysin acts as an intramolecular chaperone when expressed
      in trans with the mature sequence in Escherichia coli.
AB  - The zinc metalloendopeptidase, thermolysin (EC 3.4.24.27) produced by Bacillus
      thermoproteolyticus serves as a model of important physiological enzymes such as
      neprilysin, angiotensin converting enzyme and endothelin converting enzyme.
      Thermolysin is synthesised as a pre-proenzyme, with an N-terminal prosequence of
      204 residues and a mature sequence of 316 residues. The prosequence facilitates
      the folding of the denatured mature sequence in vitro and the cleavage of the
      peptide bond linking the pro and mature sequences occurs by an autocatalytic,
      intramolecular process. With the aim to study the role of the prosequence in vivo
      and to produce active mutants for structural studies, the mature sequence of
      thermolysin has now been expressed in Escherichia coli, either alone or with the
      prosequence as an independent polypeptide, i.e. in trans form. In addition, the
      mature sequence of an inactive mutant in which Glu143 involved in the catalytic
      process was replaced by Ala has also been expressed in trans with the
      prosequence. The results show that the pro-sequence is required to obtain active
      thermolysin and that a covalent link with the mature sequence is not necessary
      for the correct folding of the protease in vivo. Moreover, when expressed in E.
      coli (in trans with the prosequence), the yield of correctly folded E143A mutant
      was similar to that of the wild-type protease, whereas no mature enzyme was
      detected when it was expressed as a pre-proenzyme in Bacillus subtilis. These
      results demonstrate that the thermolysin prosequence acts as an intramolecular
      chaperone in vivo and open the way to structural studies of catalytic site
      mutants produced in large quantities in E. coli.

PMID- 9925775
TI  - Analysis of zinc fingers optimized via phage display: evaluating the utility of a
      recognition code.
AB  - Cys2His2 zinc finger proteins are composed of modular DNA-binding domains and
      provide an excellent framework for the design and selection of proteins with
      novel site specificity. Crystal structures of zinc finger-DNA complexes have
      shown that many Cys2His2 zinc fingers use a conserved docking arrangement that
      juxtaposes residues at key positions in the "recognition helix" with
      corresponding base positions in the three to four base-pair subsite. Several
      groups have proposed that specificity can be explained with a zinc finger-DNA
      recognition code that correlates specific amino acids at these key positions in
      the alpha-helix with specific bases in each position of the corresponding
      subsite. Here, we explore the utility of such a code through detailed studies of
      zinc finger variants selected via phage display. These proteins provide
      interesting systems for detailed analysis since they have affinities and
      specificities for their sites similar to those of naturally occurring DNA-binding
      proteins. Comparisons are facilitated by the fact that only key DNA-binding
      residues are varied in each finger while leaving all other regions of the
      structure unchanged. We study these proteins in detail by (1) selecting their
      optimal binding sites and comparing these binding sites with sites that might
      have been predicted from a code; (2) by examining the "evolutionary history" of
      these proteins during the phage display protocol to look for evidence of context
      dependent effects; and (3) by reselecting finger 1 in the presence of the
      optimized finger 2/finger 3 domains to obtain further data on finger modularity.
      Our data for optimized fingers and binding sites demonstrate a clear correlation
      with contacts that would be predicted from a code. However, there are enough
      examples of context-dependent effects (not explained by any existing code) that
      selection is the most reliable method for maximizing the affinity and specificity
      of new zinc finger proteins.

PMID- 9925776
TI  - Trans-splicing ribozymes for targeted gene delivery.
AB  - Ribozymes are potential tools for genetic manipulation, and various naturally
      occurring catalytic RNAs have been dissected and used as the basis for the design
      of new endoribonuclease activities. While such cleaving ribozymes may work well
      in vitro, they have not proved to be routinely effective in depleting living
      cells of the chosen target RNA. Recently, trans-splicing ribozymes have been
      employed to repair mutant mRNAs in vivo. We have designed modified trans-splicing
      ribozymes with improved biological activity. These allow accurate splicing of a
      new 3' exon sequence into a chosen site within a target RNA, and in frame fusion
      of the exon can result in expression of a new gene product. These trans-splicing
      ribozymes contain catalytic sequences derived from a self-splicing group I
      intron, which have been adapted to a chosen target mRNA by fusion of a region of
      extended complementarity to the target RNA and precise alteration of the guide
      sequences required for substrate recognition. Both modifications are required for
      improved biological activity of the ribozymes. Whereas cleaving ribozymes must
      efficiently deplete a chosen mRNA species to be effective in vivo, even
      inefficient trans-splicing can allow the useful expression of a new gene
      activity, dependent on the presence of a chosen RNA. We have targeted trans
      splicing ribozymes against mRNAs of chloramphenicol acetyltransferase, human
      immunodeficiency virus, and cucumber mosaic virus, and demonstrated trans
      splicing and delivery of a marker gene in Escherichia coli cells. The improved
      trans-splicing ribozymes may be tailored for virtually any target RNA, and
      provide a new tool for triggering gene expression in specific cell types.

PMID- 9925777
TI  - Synergistic stimulation of HIV-1 rev-dependent export of unspliced mRNA to the
      cytoplasm by hnRNP A1.
AB  - The structural and accessory proteins of human immunodeficiency virus type 1 are
      expressed by unspliced or partially spliced mRNAs. Efficient transport of these
      mRNAs from the nucleus requires the binding of the viral nuclear transport
      protein Rev to an RNA stem-loop structure called the RRE (Rev response element).
      However, the RRE does not permit Rev to stimulate the export of unspliced mRNAs
      from the efficiently spliced beta-globin gene in the absence of additional cis
      acting RNA regulatory signals. The p17gag gene instability (INS) element contains
      RNA elements that can complement Rev activity. In the presence of the INS element
      and the RRE, Rev permits up to 30 % of the total beta-globin mRNA to be exported
      to the cytoplasm as unspliced mRNA. Here, we show that a minimal sequence of 30
      nt derived from the 5' end of the p17 gag gene INS element (5' INS) is functional
      and permits the export to the cytoplasm of 14% of the total beta-globin mRNA as
      unspliced pre-mRNA. Gel mobility shift assays and UV cross-linking experiments
      have shown that heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and a cellular
      RNA-binding protein of 50 kDa form a complex on the 5' INS. Mutants in the 5' INS
      that prevent hnRNP A1 and 50 kDa protein binding are inactive in the transport
      assay. To confirm that the hnRNP A1 complex is responsible for INS activity, a
      synthetic high-affinity binding site for hnRNP A1 was also analysed. When the
      high affinity hnRNP A1 binding site was inserted into the beta-globin reporter,
      Rev was able to increase the cytoplasmic levels of unspliced mRNAs to 14%. In
      contrast, the mutant hnRNP A1 binding site, or binding sites for hnRNP C and L
      are unable to stimulate Rev-mediated RNA transport. We conclude that hnRNP A1 is
      able to direct unspliced globin pre-mRNA into a nuclear compartment where it is
      recognised by Rev and then transported to the cytoplasm.

PMID- 9925778
TI  - Integration of the colicin A pore-forming domain into the cytoplasmic membrane of
      Escherichia coli.
AB  - The pore-forming domain of colicin A (pfColA) fused to a prokaryotic signal
      peptide (sp-pfColA) inserted into the inner membrane of Escherichia coli and
      apparently formed a functional channel, when generated in vivo. We investigated
      pfColA functional activity in vivo by the PhoA gene fusion approach, combined
      with cell fractionation and protease susceptibility experiments. Alkaline
      phosphatase was fused to the carboxy-terminal end of each of the ten alpha
      helices of sp-pfColA to form a series of differently sized fusion proteins. We
      suggest that the alpha-helices anchoring pfColA in the membrane are first
      translocated into the periplasm. We identify two domains that anchor pfColA to
      the membrane in vivo: domain 1, extending from helix 1 to helix 8, which contains
      the voltage-responsive segment and domain 2 consisting of the hydrophobic helices
      8 and 9. These two domains function independently. Fusion proteins with a
      mutation inactivating the voltage-responsive segment or with a domain 1 lacking
      helix 8 were peripherally associated with the outside of the inner membrane, and
      were therefore digested by proteases added to spheroplasts. In contrast, fusion
      proteins with a functional domain 1 were protected from proteases, suggesting as
      expected that most of domain 1 is inserted into the membrane or is indeed
      translocated to the cytoplasm during pfColA channel opening.

PMID- 9925779
TI  - Classification of Arabidopsis thaliana gene sequences: clustering of coding
      sequences into two groups according to codon usage improves gene prediction.
AB  - While genomic sequences are accumulating, finding the location of the genes
      remains a major issue that can be solved only for about a half of them by
      homology searches. Prediction methods are thus required, but unfortunately are
      not fully satisfying. Most prediction methods implicitly assume a unique model
      for genes. This is an oversimplification as demonstrated by the possibility to
      group coding sequences into several classes in Escherichia coli and other
      genomes. As no classification existed for Arabidopsis thaliana, we classified
      genes according to the statistical features of their coding sequences. A
      clustering algorithm using a codon usage model was developed and applied to
      coding sequences from A. thaliana, E. coli, and a mixture of both. By using it,
      Arabidopsis sequences were clustered into two classes. The CU1 and CU2 classes
      differed essentially by the choice of pyrimidine bases at the codon silent sites:
      CU2 genes often use C whereas CU1 genes prefer T. This classification
      discriminated the Arabidopsis genes according to their expressiveness, highly
      expressed genes being clustered in CU2 and genes expected to have a lower
      expression, such as the regulatory genes, in CU1. The algorithm separated the
      sequences of the Escherichia-Arabidopsis mixed data set into five classes
      according to the species, except for one class. This mixed class contained 89 %
      Arabidopsis genes from CU1 and 11 % E. coli genes, mostly horizontally
      transferred. Interestingly, most genes encoding organelle-targeted proteins,
      except the photosynthetic and photoassimilatory ones, were clustered in CU1. By
      tailoring the GeneMark CDS prediction algorithm to the observed coding sequence
      classes, its quality of prediction was greatly improved. Similar improvement can
      be expected with other prediction systems.

PMID- 9925780
TI  - Cation transport: an example of structural based selectivity.
AB  - Through the high-resolution structure of the gramicidin A channel in lamellar
      phase lipids and the characterization of specific ion peptide interactions,
      fundamental principles for ion channel selectivity and conductance efficiency are
      illustrated with atomic resolution detail. Delocalized cation binding in the
      first turn of the helix reduces the unfavorable entropy contribution upon
      binding. Stepwise dehydration minimizes the energy barrier for cation entry and
      provides valence selectivity in this channel. Three or more water molecules in
      the monovalent cation binding site result in flexibility in the cation solvation
      environment causing weak cation size selectivity. Lack of cation induced
      structural modification avoids the formation of a significant energy barrier,
      thus permitting efficient cation transport.

PMID- 9925781
TI  - Folding and assembly of an antibody Fv fragment, a heterodimer stabilized by
      antigen.
AB  - The folding and assembly of the Fv fragment of the phosphorylcholine binding
      antibody McPC603, a non-covalent heterodimer of the variable domains VH and VL,
      was investigated. Since both domains, each engineered for stability and folding
      efficiency, could now be obtained in native and soluble form by themselves,
      fluorescence spectra of VH and VL in unfolded, folded and associated states can
      be reported. VH and VL only associate when they are native, and the stability of
      the heterodimer is strongly increased in the presence of antigen. VH rapidly
      folds into an hyperfluorescent intermediate, and the native state is reached in
      two parallel, proline-independent reactions. VL displays two fast refolding
      reactions, which are followed by two slower phases, limited by proline cis/trans
      isomerization. The rate-limiting step for both the Fv and the scFv (single-chain
      Fv) fragment is the formation of the native VH-VL interface, which depends on
      ProL95 being in cis. The folding of the Fv fragment is fast after short-term
      denaturation or in the presence of proline cis/trans-isomerase catalysis, but the
      scFv fragment falls into a kinetic trap, observed by the persistence of the slow
      phases under all conditions. Furthermore, the scFv fragment, but not the Fv
      fragment, gives rise to premature interface formation, indicated by the
      fluorescence spectra and a much higher transient binding of 8-anilino-1
      naphthalene sulfonate. The analysis of the folding pathway of the domains VH and
      VL in isolation and in non-covalent and covalent assemblies should provide
      helpful insights into the folding of multimeric proteins in general, and for the
      further engineering of stable and well-folding antibody fragments in particular.

PMID- 9925782
TI  - Mechanism of inhibition of DNA (cytosine C5)-methyltransferases by
      oligodeoxyribonucleotides containing 5,6-dihydro-5-azacytosine.
AB  - A key step in the predicted mechanism of enzymatic transfer of methyl groups from
      S-adenosyl-l-methionine (AdoMet) to cytosine residues in DNA is the transient
      formation of a dihydrocytosine intermediate covalently linked to cysteine in the
      active site of a DNA (cytosine C5)-methyltransferase (DNA C5-MTase).
      Crystallographic analysis of complexes formed by HhaI methyltransferase (M.HhaI),
      AdoMet and a target oligodeoxyribonucleotide containing 5-fluorocytosine
      confirmed the existence of this dihydrocytosine intermediate. Based on the
      premise that 5,6-dihydro-5-azacytosine (DZCyt), a cytosine analog with an sp3
      hybridized carbon (CH2) at position 6 and an NH group at position 5, could mimic
      the non-aromatic character of the cytosine ring in this transition state, we
      synthesized a series of synthetic substrates for DNA C5-MTase containing DZCyt.
      Substitution of DZCyt for target cytosines in C-G dinucleotides of single
      stranded or double-stranded oligodeoxyribonucleotide substrates led to complete
      inhibition of methylation by murine DNA C5-MTase. Substitution of DZCyt for the
      target cytosine in G-C-G-C sites in double-stranded oligodeoxyribonucleotides had
      a similar effect on methylation by M. HhaI. Oligodeoxyribonucleotides containing
      DZCyt formed a tight but reversible complex with M.HhaI, and were consistently
      more potent as inhibitors of DNA methylation than oligodeoxyribonucleotides
      identical in sequence containing 5-fluorocytosine. Crystallographic analysis of a
      ternary complex involving M.HhaI, S-adenosyl-l-homocysteine and a double-stranded
      13-mer oligodeoxyribonucleotide containing DZCyt at the target position showed
      that the analog is flipped out of the DNA helix in the same manner as cytosine, 5
      methylcytosine, and 5-fluorocytosine. However, no formation of a covalent bond
      was detected between the sulfur atom of the catalytic site nucleophile, cysteine
      81, and the pyrimidine C6 carbon. These results indicate that DZCyt can occupy
      the active site of M.HhaI as a transition state mimic and, because of the high
      degree of affinity of its interaction with the enzyme, it can act as a potent
      inhibitor of methylation.

PMID- 9925783
TI  - The high-resolution structure of the triplex formed by the GAA/TTC triplet repeat
      associated with Friedreich's ataxia.
AB  - Expansions of the triplet repeat, GAA/TTC, inside the first intron of the
      frataxin gene causes Friedreich's ataxia (FRDA). It was of interest to us to
      examine whether the FRDA repeat forms an unusual DNA structure, since formation
      of such structure during replication may cause its expansion. Here, we show that
      the FRDA repeat forms a triplex in which the TTC strand folds on either side of
      the same GAA strand. We have determined the high-resolution NMR structures of two
      intramolecularly folded FRDA triplexes, (GAA)2T4(TTC)2T4(CTT)2 and
      (GAA)2T4(TTC)2T2CT2(CTT)2 with T.A.T and C+.G.C triads. T4 represents a synthetic
      loop sequence, whereas T2CT2 is the natural loop-folding sequence of the TTC
      strand. We have also made use of site-specific 15N-labeling of the cytosine
      residues to investigate their protonation status and their interaction with other
      protons. We show that the cytosine residues of the Hoogsteen C+.G pairs in this
      triplex are protonated close to physiological pH. Therefore, it appears that the
      triplex formation offers a plausible explanation for the expansion of the GAA/TTC
      repeats in FRDA.

PMID- 9925784
TI  - A dynamic programming algorithm for RNA structure prediction including
      pseudoknots.
AB  - We describe a dynamic programming algorithm for predicting optimal RNA secondary
      structure, including pseudoknots. The algorithm has a worst case complexity of
      O(N6) in time and O(N4) in storage. The description of the algorithm is complex,
      which led us to adopt a useful graphical representation (Feynman diagrams)
      borrowed from quantum field theory. We present an implementation of the algorithm
      that generates the optimal minimum energy structure for a single RNA sequence,
      using standard RNA folding thermodynamic parameters augmented by a few parameters
      describing the thermodynamic stability of pseudoknots. We demonstrate the
      properties of the algorithm by using it to predict structures for several small
      pseudoknotted and non-pseudoknotted RNAs. Although the time and memory demands of
      the algorithm are steep, we believe this is the first algorithm to be able to
      fold optimal (minimum energy) pseudoknotted RNAs with the accepted RNA
      thermodynamic model.

PMID- 9925785
TI  - Major groove binding of the tRNA/mRNA complex to the 16 S ribosomal RNA decoding
      site.
AB  - We propose a detailed three-dimensional model, with atomic detail, for the
      structure of the Escherichia coli 16 S rRNA decoding site in a complex with mRNA
      and the A and P-site tRNAs. Model building began with four primary assumptions:
      (1) A and P-site tRNA conformations are identical with those seen in the tRNA
      crystal structure; (2) A and P-site tRNAs adopt an S-type orientation upon
      binding mRNA in the ribosome; (3) A1492 and A1493 bind non-specifically to the
      mRNA through a series of hydrogen bonds; and (4) C1400 lies in close proximity to
      the P-site tRNA wobble base in order to satisfy a UV-induced photocrosslink
      formed between the two residues. We have models with both major groove and minor
      groove binding of the tRNA/mRNA complex to the decoding site RNA, and conclude
      that major groove binding is more likely. Both classes of models maintain
      structural features reported in the NMR structure of the A-site region of the
      decoding site RNA with bound paromomycin. We also present models for the
      tRNA/mRNA complex bound to the decoding site RNA in the presence of the
      aminoglycoside paromomycin. We discuss possible mechanisms for ribosomal proof
      reading and antibiotic disruption of this proofreading.

PMID- 9925786
TI  - Crystal structure of the E166A mutant of extended-spectrum beta-lactamase Toho-1
      at 1.8 A resolution.
AB  - Bacterial resistance to beta-lactams is mainly due to the production of beta
      lactamase. Especially through the production of extended-spectrum beta-lactamases
      (ESBLs), bacteria have acquired resistance not only to penicillins, but also to
      expanded-spectrum cephems. Here, we describe the crystal structure of the E166A
      mutant of class A beta-lactamase Toho-1 at 1.8 A resolution, the first reported
      tertiary structure of an ESBL. Instead of the wild-type enzyme, a mutant Toho-1,
      in which Glu166 was replaced with alanine, was used for this study, because of
      the strong tendency of the wild-type enzyme to form twinned crystals. The overall
      structure of Toho-1 is similar to the crystal structures of non-ESBLs, with no
      pronounced backbone rearrangement of the framework. However, there are some
      notable local changes. First, a difference in the disposition of an arginine
      residue, which is at position 244 in non-ESBLs but at position 276 in Toho-1 and
      other ESBLs, was revealed and the role of this arginine residue is discussed.
      Moreover, changes in the hydrogen-bonding pattern and in the formation of the
      hydrophobic core were also observed near the Omega loop. In particular, the lack
      of hydrogen bonds in the vicinity of the Omega loop could be a cause of the
      extended substrate specificity of Toho-1. Through the generation of a model for
      the enzyme-substrate complex, a conformational change of Toho-1 occurring on
      complex formation is discussed based on the active-site cleft structure and the
      substrate profile.

PMID- 9925787
TI  - Structure of extracellular tissue factor complexed with factor VIIa inhibited
      with a BPTI mutant.
AB  - The event that initiates the extrinsic pathway of blood coagulation is the
      association of coagulation factor VIIa (VIIa) with its cell-bound receptor,
      tissue factor (TF), exposed to blood circulation following tissue injury and/or
      vascular damage. The natural inhibitor of the TF.VIIa complex is the first Kunitz
      domain of tissue factor pathway inhibitor (TFPI-K1). The structure of TF. VIIa
      reversibly inhibited with a potent (Ki=0.4 nM) bovine pancreatic trypsin
      inhibitor (BPTI) mutant (5L15), a homolog of TFPI-K1, has been determined at 2.1
      A resolution. When bound to TF, the four domain VIIa molecule assumes an extended
      conformation with its light chain wrapping around the framework of the two domain
      TF cofactor. The 5L15 inhibitor associates with the active site of VIIa similar
      to trypsin-bound BPTI, but makes several unique interactions near the perimeter
      of the site that are not observed in the latter. Most of the interactions are
      polar and involve mutated positions of 5L15. Of the eight rationally engineered
      mutations distinguishing 5L15 from BPTI, seven are involved in productive
      interactions stabilizing the enzyme-inhibitor association with four contributing
      contacts unique to the VIIa.5L15 complex. Two additional unique interactions are
      due to distinguishing residues in the VIIa sequence: a salt bridge between Arg20
      of 5L15 and Asp60 of an insertion loop of VIIa, and a hydrogen bond between
      Tyr34O of the inhibitor and Lys192NZ of the enzyme. These interactions were used
      further to model binding of TFPI-K1 to VIIa and TFPI-K2 to factor Xa, the
      principal activation product of TF.VIIa. The structure of the ternary protein
      complex identifies the determinants important for binding within and near the
      active site of VIIa, and provides cogent information for addressing the manner in
      which substrates of VIIa are bound and hydrolyzed in blood coagulation. It should
      also provide guidance in structure-aided drug design for the discovery of potent
      and selective small molecule VIIa inhibitors.

PMID- 9925788
TI  - NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein
      Vpr: molecular insights into its biological functions.
AB  - The HIV-1 regulatory protein Vpr (96 amino acid residues) is incorporated into
      the virus particle through a mechanism involving its interaction with the C
      terminal portion of Gag. Vpr potentiates virus replication by interrupting cell
      division in the G2 phase and participates in the nuclear transport of proviral
      DNA. The domain encompassing the 40 C-terminal residues of Vpr was shown to be
      involved in cell cycle arrest and binding of nucleocapsid protein NCp7, and
      suggested to promote nuclear provirus transfer. Accordingly, we show here that
      the synthetic 52-96 but not 1-51 sequences of Vpr interact with HIV-1 RNA. Based
      on these results, the structure of (52-96)Vpr was analysed by two-dimensional 1H
      NMR in aqueous TFE (30%) solution and refined by restrained molecular dynamics.
      The structure is characterized by a long (53-78) amphipathic alpha-helix,
      followed by a less defined (79-96) C-terminal domain. The Leu60 and Leu67 side
      chains are located on the hydrophobic side of the helix, suggesting their
      involvement in Vpr dimerization through a leucine zipper-type mechanism.
      Accordingly, their replacement by Ala eliminates Vpr dimerization in the two
      hybrid systems, while mutations of Ile74 and Ile81 have no effect. This was
      confirmed by gel filtration measurements and circular dichroism, which also
      showed that the alpha-helix still exists in (52-96)Vpr and its Ala60, Ala67
      mutant in the presence and absence of TFE. Based on these results, a model of the
      coiled-coil Vpr dimer has been described, and its biological relevance as well as
      that of the structural characteristics of the 52-96 domain for the different
      functions of Vpr, including HIV-1 RNA binding, are discussed.

PMID- 9925789
TI  - Solution structure of the carboxyl terminus of a human class Mu glutathione S
      transferase: NMR assignment strategies in large proteins.
AB  - Strategies to obtain the NMR assignments for the HN, N, CO, Calpha and Cbeta
      resonance frequencies for the human class mu glutathione-S-transferase GSTM2-2
      are reported. These assignments were obtained with deuterated protein using a
      combination of scalar and dipolar connectivities and various specific labeling
      schemes. The large size of this protein (55 kDa, homodimer) necessitated the
      development of a novel pulse sequence and specific labeling strategies. These
      aided in the identification of residue type and were essential components in
      determining sequence specific assignments. These assignments were utilized in
      this study to characterize the structure and dynamics of the carboxy-terminal
      residues in the unliganded protein. Previous crystallographic studies of this
      enzyme in complex with glutathione suggested that this region may be disordered,
      and that this disorder may be essential for catalysis. Furthermore, in the
      related class alpha protein extensive changes in conformation of the C terminus
      are observed upon ligand binding. On the basis of the results presented here, the
      time-averaged conformation of the carboxyl terminus of unliganded GSTM2-2 is
      similar to that seen in the crystal structure. NOE patterns and 1H-15N
      heteronuclear nuclear Overhauser enhancements suggest that this region of the
      enzyme does not undergo motion on a rapid time scale.

PMID- 9925790
TI  - Temperature dependence of intramolecular dynamics of the basic leucine zipper of
      GCN4: implications for the entropy of association with DNA.
AB  - The basic leucine zipper domain of the yeast transcription factor GCN4 consists
      of a C-terminal leucine zipper and an N-terminal basic DNA-binding region that
      achieves a stable structure only after association with DNA. Backbone dynamics of
      a peptide encompassing the basic and leucine zipper bZip domain (residues 226
      281) are described using NMR spectroscopy. The 15N longitudinal relaxation rates,
      15N transverse relaxation rates, and {1H}-15N nuclear Overhauser effects were
      measured for the backbone amide nitrogen atoms at 290 K, 300 K, and 310 K. The
      relaxation data were interpreted using reduced spectral density mapping to
      determine values of the spectral density function, J(omega), at the frequencies
      0, omegaN, and 0.87omegaH to characterize overall and intramolecular motions on
      picosecond-nanosecond timescales. To account for the temperature dependence of
      overall rotational diffusion, the J(0) values were normalized using Stoke's Law.
      At 310 K, the 13Calpha and 13CO chemical shifts in conjunction with the spectral
      density values indicate that the leucine zipper sequence forms a highly ordered
      alpha-helix, while the basic region populates an ensemble of highly dynamic
      transient structures with substantial helical character. The normalized values of
      J(0) and the values of J(0.87omegaH) for residues in the leucine zipper
      dimerization domain are independent of temperature. In contrast, residues in the
      basic region exhibit pronounced increases in the normalized J(0) and decreases in
      J(0.87omegaH) as temperature is decreased. A strong correlation exists between
      the temperature dependence of 13CO chemical shifts and of J(0.87omegaH). These
      results suggest that, for the basic region, lowering the temperature increases
      the population of transient helical conformations, and concomitantly reduces the
      amplitude or timescale of conformational fluctuations on picosecond-nanosecond
      timescales. Changes in the conformational dynamics of the peptide backbone of the
      basic region that accompany DNA binding contribute to the overall thermodynamics
      of complex formation. The change in backbone conformational entropy derived from
      NMR spin-relaxation data agrees well with the result calculated from calorimetric
      measurements. Restriction of the conformational space accessible to the basic
      region may significantly reduce the entropic cost associated with formation of
      the basic region helices consequent to DNA binding.

PMID- 9925791
TI  - Structural study of the lipomannans from Mycobacterium bovis BCG:
      characterisation of multiacylated forms of the phosphatidyl-myo-inositol anchor.
AB  - A biosynthetic filiation is postulated between the mycobacterial phosphatidyl-myo
      inositol mannosides (PIMs), the lipomannans (LMs) and the lipoarabinomannans
      (LAMs), the major antigens of the envelopes. Moreover, as the PI anchor is
      thought to play a role in the biological functions of the LAMs, we characterized
      the lipid moiety of the PI anchor from Mycobacterium bovis BCG cellular LMs.
      Their structure was investigated along with that of a purified tetra-acylated
      form of PIM2 (Ac4PIM2). A two-dimensional 1H-31P heteronuclear multiple quantum
      correlation homonuclear Hartmann-Hahn spectroscopy study of Ac4PIM2 unambiguously
      localised a fourth fatty acid on the C3 of the myo-Ins beside the fatty acids
      already described on the C1 and C2 position of the glycerol and on the C6
      position of the mannose. This analytical strategy was extended to the structural
      study of the cellular LM anchor. Using an appropriate solvent system, the one
      dimensional 31P NMR spectrum exhibited four major resonances typifying the LM
      populations. These populations differed in number and location of the fatty
      acids. For one of these populations, we established the presence of an extra
      fatty acid on the C3 of the myo-Ins of the LM anchor. The fact that both types of
      molecules have an elaborated anchor in common, indicates that cellular LMs are
      multimannosylated forms of PIMs. In addition, the LM mannan core structure was
      analysed by two-dimensional NMR, pointing to a high level of branching by single
      alpha1-->2 Manp side-chains.

PMID- 9925792
TI  - Conformations of peptide fragments from the FK506 binding protein: comparison
      with the native and urea-unfolded states.
AB  - The helix-forming tendency of seven peptide fragments corresponding with the
      entire sequence of the FK506 binding protein (FKBP) has been investigated in
      aqueous buffer and in 2,2,2-trifluoroethanol (TFE) using CD and NMR spectroscopy.
      All fragments exhibited random coil conformations in aqueous buffer, whereas the
      amount of helix induced in the peptide fragments by TFE varied. The fragment with
      the highest degree of helicity in TFE corresponded with the single (alpha-helix
      in native FKBP. Fragments corresponding with beta-strands 2 and 3 also exhibited
      strong propensity towards helix formation. In contrast, the fragment
      corresponding with beta-strand 1 did not form helix in TFE. The inherent helix
      forming tendencies are interpreted in light of the native structure to suggest
      possible folding nucleation sites. Conformational sampling in each peptide
      fragment was also compared with that observed in urea-denatured FKBP. With the
      exception of the fragment corresponding with beta-strand 2, the formation of
      helical structures in the peptide fragments in TFE was correlated with the
      observation of turn and/or helix conformers in urea-unfolded FKBP. Surprisingly,
      peptide fragments in aqueous solution were less structured than the corresponding
      regions in urea-denatured FKBP. The conformational differences between the
      peptide fragments and unfolded FKBP were not due to the urea buffer or to
      differences in their rotational correlation times. We conclude that local amino
      acid interactions are not generally sufficient to account for the formation of
      non-random conformations in unfolded FKBP. Formation of non-random structures in
      unfolded FKBP may require stabilization of incipient turn or helical
      conformations through transient contact with non-local non-polar residues.

PMID- 9925793
TI  - The atomic structure of protein-protein recognition sites.
AB  - The non-covalent assembly of proteins that fold separately is central to many
      biological processes, and differs from the permanent macromolecular assembly of
      protein subunits in oligomeric proteins. We performed an analysis of the atomic
      structure of the recognition sites seen in 75 protein-protein complexes of known
      three-dimensional structure: 24 protease-inhibitor, 19 antibody-antigen and 32
      other complexes, including nine enzyme-inhibitor and 11 that are involved in
      signal transduction.The size of the recognition site is related to the
      conformational changes that occur upon association. Of the 75 complexes, 52 have
      "standard-size" interfaces in which the total area buried by the components in
      the recognition site is 1600 (+/-400) A2. In these complexes, association
      involves only small changes of conformation. Twenty complexes have "large"
      interfaces burying 2000 to 4660 A2, and large conformational changes are seen to
      occur in those cases where we can compare the structure of complexed and free
      components. The average interface has approximately the same non-polar character
      as the protein surface as a whole, and carries somewhat fewer charged groups.
      However, some interfaces are significantly more polar and others more non-polar
      than the average. Of the atoms that lose accessibility upon association, half
      make contacts across the interface and one-third become fully inaccessible to the
      solvent. In the latter case, the Voronoi volume was calculated and compared with
      that of atoms buried inside proteins. The ratio of the two volumes was 1.01 (+/
      0.03) in all but 11 complexes, which shows that atoms buried at protein-protein
      interfaces are close-packed like the protein interior. This conclusion could be
      extended to the majority of interface atoms by including solvent positions
      determined in high-resolution X-ray structures in the calculation of Voronoi
      volumes. Thus, water molecules contribute to the close-packing of atoms that
      insure complementarity between the two protein surfaces, as well as providing
      polar interactions between the two proteins.

PMID- 9925794
TI  - Intermolecular cleavage by UmuD-like enzymes: identification of residues required
      for cleavage and substrate specificity.
AB  - The UmuD-like proteins are best characterized for their role in damage-induced
      SOS mutagenesis. An essential step in this process is the enzymatic self
      processing of the UmuD-like proteins. This reaction is thought to occur either
      via an intramolecular or intermolecular self-cleavage mechanism. Here, we
      demonstrate that it can also occur via an heterologous intermolecular cleavage
      reaction. The Escherichia coli UmuD enzyme demonstrated the broadest substrate
      specificity, cleaving both E. coli and Salmonella typhimurium UmuD substrates in
      vivo. In comparison, the wild-type S. typhimurium UmuD (UmuDSt) and MucA enzymes
      catalyzed intermolecular self-cleavage, but did not facilitate heterologous
      cleavage. Heterologous cleavage by the UmuDSt enzyme was, however, observed with
      chimeric UmuD substrates that possess residues 30-55 of UmuDSt. We have further
      localized the residue predominantly responsible for UmuDSt-catalyzed heterologous
      cleavage to Ser50 in the substrate molecule. We hypothesize that changes at this
      residue affect the positioning of the cleavage site of a substrate molecule
      within the catalytic cleft of the UmuDSt enzyme by affecting the formation of a
      so-called UmuD "filament-dimer". This hypothesis is further supported by the
      observation that mutations known to disrupt an E. coli UmuD' filament dimer also
      block intermolecular UmuDEc cleavage.

PMID- 9925795
TI  - The mitochondrial permeability transition mediates both necrotic and apoptotic
      death of hepatocytes exposed to Br-A23187.
AB  - A23187 and related Ca2+ ionophores are widely used to study Ca2+-dependent cell
      injury. Here, using laser scanning confocal microscopy and parameter-indicating
      fluorophores, we investigated the role of the mitochondrial permeability
      transition (MPT) in Br-A23187 toxicity to cultured rat hepatocytes. After 10
      microM Br-A23187, over 60% of hepatocytes lost viability within 1 h. This
      necrotic cell killing was preceded by increased mitochondrial free Ca2+,
      mitochondrial depolarization, and onset of the MPT. Cyclosporin A (CsA), a
      blocker of the permeability transition pore, prevented the MPT and cell killing
      but had no effect on increased mitochondrial free Ca2+ and depolarization after
      Br-A23187. To determine whether Br-A23187-induced cell killing was linked to loss
      of cellular ATP supply, hepatocytes were incubated with fructose and oligomycin,
      a source of glycolytic ATP and an inhibitor of the uncoupler-stimulated
      mitochondrial ATPase, respectively. Fructose plus oligomycin prevented cell
      killing after Br-A23187 but not the MPT. When fructose plus oligomycin prevented
      necrotic cell killing, apoptosis developed after 10 h. When cells were treated
      additionally with CsA, these apoptotic changes were prevented. In conclusion, the
      MPT mediates Br-A23187 cytotoxicity. Acutely, the MPT causes mitochondrial
      uncoupling and profound ATP depletion, which leads to necrotic cell death.
      However, when glycolytic ATP generation is available, the MPT induces apoptosis.
      CsA blocks the MPT and prevents both necrotic and apoptotic cell killing after Br
      A23187.

PMID- 9925796
TI  - Nitroarene reduction and generation of free radicals by cell-free extracts of
      wild-type, and nitroreductase-deficient and -enriched Salmonella typhimurium
      strains used in the umu gene induction assay.
AB  - Studies of the enzymatic properties of cell-free extracts prepared from overnight
      cultures of the normal, and nitroreductase-deficient and -enriched strains of
      Salmonella typhimurium, designed for use in the umu gene induction assay of Oda
      et al. (1992), were undertaken in an effort to clarify the nature of
      nitroreductase deficiency in relation to mutagenicity. The ability of these
      strains to promote oxygen consumption and free radical intermediates of
      representative nitroarene substrates was measured, respectively, by oxygen
      polarography and electron spin resonance (ESR) spectroscopy. The substrates 4
      nitropyridine N-oxide (4NPO) and 4-nitroquinoline N-oxide (4NQO) stimulated the
      rate and extent of NADH-dependent oxygen consumption catalyzed by cell-free
      extracts prepared from wild-type, and nitroreductase-deficient and -enriched
      strains. The extent of oxygen consumption was greater than stoichiometric with
      respect to the amount of nitroaromatic substrate, which implied one-electron
      reduction of 4NQO by these bacterial extracts and subsequent redox cycling with
      oxygen. ESR spectroscopy confirmed the production of free radical metabolites of
      the nitroarene substrates, which were inferred by the oxygen consumption studies.
      At equal protein concentrations the cell-free extracts of each strain catalyzed
      univalent reduction of 4NPO yielding the 59 line signal characteristic of the
      4NPO nitro anion radical. This ESR signal was potently inhibited by the
      flavoprotein inhibitors CuSO4 and PCMB, albeit a twofold or higher concentration
      of both inhibitors was required to inhibit the signal produced by extract from
      the nitroreductase-deficient strain than that produced by the other strains. The
      results indicate that the nitroreductase-deficient strain of Salmonella
      typhimurium developed for use in the umu gene induction assay is not deficient in
      either one-electron nitro group or quinone reductase activity.

PMID- 9925797
TI  - Disposition of inorganic mercury following biliary obstruction and chemically
      induced glutathione depletion: dispositional changes one hour after the
      intravenous administration of mercuric chloride.
AB  - Influences of biliary obstruction and systemic depletion of glutathione (GSH) on
      the disposition of a low nontoxic iv dose of inorganic mercury were evaluated in
      rats in the present study. Specifically, the disposition of mercury in the
      kidneys, liver, small and large intestines, and blood was assessed 1 h after the
      injection of 0.5 micromol/kg mercuric chloride in control rats and rats
      pretreated with acivicin, buthionine sulfoximine (BSO), or diethylmaleate (DEM)
      that did or did not undergo acute biliary ligation prior to the injection of
      mercury. Among the groups that did not undergo biliary ligation, the
      pretreatments used to alter GSH status systemically had varying effects on the
      disposition of inorganic mercury in the kidneys, liver, intestines, and blood.
      Biliary ligation caused the net renal accumulation of mercury to decrease under
      all pretreatment conditions. By contrast, biliary ligation caused significant
      increases in the hepatic burden of mercury in all pretreatment groups except the
      acivicin-pretreated group. Blood levels of mercury also increased as a result of
      biliary ligation, regardless of the type of pretreatment used. Evidence for a
      secretory-like movement of mercury into the lumen of the intestines is also
      provided in the animals that underwent biliary ligation. The present findings
      indicate that biliary ligation combined with methods used to alter GSH status
      systemically have additive effects with respect to causing reductions in the net
      renal accumulation of mercury. In addition, the findings indicate that at least
      some fraction of the renal accumulation of inorganic mercury is linked
      mechanistically to the hepatobiliary system.

PMID- 9925798
TI  - Reversible long-term toxicity of epristeride in beagle dogs.
AB  - Epristeride (17beta-N-t-butylcarboxamide-androst-3, 5-diene-3-carboxylic acid) is
      an uncompetitive inhibitor of steroid 5alpha-reductase, the enzyme that converts
      testosterone to dihydrotestosterone (DHT), and has been shown to retard the
      growth of hyperplastic prostates. The objective of the current investigation was
      to research the toxic effects of epristeride and to demonstrate its reversible.
      In the experiment, 18 beagle dogs (male, about 6 months old) were used and
      divided into six groups, with each group containing three dogs. Groups A and B
      were placebo-treated for 180 and 240 days, Groups C and D were treated with 10
      and 100 mg/kg epristeride for 180 days, and Groups E and F were treated with 10
      and 100 mg/kg epristeride for 180 days and then were placebo-treated for 60 days
      (total 240 days), respectively. Routine analyses were performed at the 1st, 30th,
      90th, 180th, and 240th days, and the dogs were autopsied at the 180th or 240th
      day for systemic examination and measured for relative DNA content in single
      prostatic epithelial cells. Each prostate was fixed with 4% Formalin, embedded in
      paraffin, sectioned at 6 micron, and immunohistochemically stained for assaying
      the relative content (transmittance) of prostatic specific antigen (PSA) and DHT
      (%) with a microspectrophotometer at 650-nm wavelength. The results were that 180
      days of toxicity with epristeride (100 mg/kg) on interstitial cells of testes and
      DNA in prostatic epithelial cells couldn't reverse during 60 days of
      convalescence and that the DHT and PSA levels in the gland, the volume of the
      gland, glandular epithelial cell height, and acinar luminal area could reverse to
      normal during the same convalescence. To our knowledge this is the first study
      documenting the toxicity of epristeride. It is necessary to further study the
      molecular and clinical toxicity of epristeride.

PMID- 9925800
TI  - Lactational exposure and neonatal kinetics of methylmercury and inorganic mercury
      in mice.
AB  - The concentration of mercury in milk and the distribution pattern in the sucking
      pup was followed over time after administration of a single iv injection of 0.5
      mg/kg body wt of 203Hg-labeled methylmercuric chloride or mercuric chloride to
      lactating mice on Day 10 of lactation. Mercury concentrations in milk of the dams
      and in whole body, blood, plasma, GI-tract, liver, kidneys, and brain of the
      offspring were followed up to 11 days after dosing (until lactational Day 21).
      Following the inorganic mercury dose to the dams, most of the mercury in milk was
      delivered to the pups during the first 24 h, but the maximum mercury
      concentration in plasma and tissues of pups was not reached until 7 days after
      dosing, indicating a prolonged absorption of inorganic mercury in the sucking
      pup. Pups of dams given methylmercury were exposed to a much lower and constant
      mercury concentration in milk. The estimated accumulated mercury dose via milk
      per pup of dams given methylmercury was less than half of that estimated after
      the inorganic mercury dose. When the accumulated dose via milk from methylmercury
      exposed dams was compared to the amount of mercury in pup's carcass (whole body
      minus GI-tract including content), it was revealed that almost all mercury
      delivered via milk was absorbed, and that the suckling pups had a very low
      elimination of mercury until lactational Day 17. Lactational exposure following a
      maternal methylmercury or inorganic mercury dose resulted in almost similar
      mercury concentrations in liver, kidneys, and plasma of the suckling, but higher
      concentrations in brain (as most 14 times) and also twice as high mercury body
      burden in the methylmercury group. Thus, differences in kinetics indicate that
      lactational exposure of methylmercury is a greater hazard for the breast-fed
      infant than inorganic mercury.

PMID- 9925799
TI  - Propanil affects transcriptional and posttranscriptional regulation of IL-2
      expression in activated EL-4 cells.
AB  - The amide-class herbicide, propanil, causes numerous immunomodulary effects in
      animal models. In the present study, we investigated the effect of propanil on IL
      2 expression and production in the murine lymphoma T cell line, EL-4. When
      supernatants of cells stimulated with phorbol 12-myristate 13-acetate in the
      presence of propanil were assessed by enzyme-linked immunosorbent assay, IL-2
      levels were dose-dependently decreased by 20 and 50 microM of propanil but not at
      10 microM. Quantitative Northern blot analysis of peak IL-2 message levels also
      showed a dose-dependent decrease. The kinetic pattern of message production,
      however, was unaffected. To determine if the reduced message production was due
      to reduced signaling or message stability, nuclear run-on and mRNA stability
      assays were performed. Nuclear run-on assays determined that the transcription
      rate of the IL-2 gene was decreased approximately 50% in the presence of 20
      microM propanil, indicating that it was able to interfere with signal
      transduction. IL-2 message stability assays also demonstrated a reduction in
      message stability. Thus, propanil appears to reduce IL-2 production by affecting
      the signal transduction pathway and IL-2 message stability.

PMID- 9925801
TI  - The role of glucuronidation in N-(3,5-dichlorophenyl)succinimide (NDPS)
      nephrotoxicity: nephrotoxic potential of NDPS and NDPS metabolites in Gunn,
      Wistar, and Fischer 344 rats.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute
      nephrotoxicant in rats. Although the mechanism of NDPS nephrotoxicity is not
      clear, our previous studies have strongly suggested that glucuronide conjugation
      of NDPS metabolite(s) is an important biotransformation reaction leading to the
      ultimate nephrotoxicant metabolite(s) mediating NDPS nephrotoxicity. In this
      study, the nephrotoxic potential of NDPS and its nephrotoxicant metabolites, N
      (3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2
      hydroxysuccinamic acid (NDHSA), was examined in Gunn rats, which contain a
      genetic deficiency in bilirubin uridine diphosphate-glucuronosyltransferase
      (UDPGT), to explore further the role of glucuronidation in NDPS nephrotoxicity.
      The nephrotoxic potential of NDPS, NDHS, and NDHSA was also examined in Wistar
      rats, the parent strain for Gunn rats and which generally have normal UDPGT
      activity. Comparisons were then made with the nephrotoxicity induced by these
      compounds in Fischer 344 (F344) rats. Age-matched male F344, homozygous (j/j)
      Gunn, and Wistar rats were used. Rats (four to eight rats/group) of each strain
      were administered NDPS (0.4 mmol/kg ip), NDHS (0.1 or 0.2 mmol/kg ip), NDHSA (0.1
      mmol/kg ip), or vehicle, and renal effects were monitored functionally and
      morphologically for 48 h. NDPS and its nephrotoxicant metabolites, NDHS and
      NDHSA, were much weaker nephrotoxicants in Gunn rats than in F344 rats, while
      Wistar rats were susceptible to the nephrotoxicity induced by NDPS, NDHS, or
      NDHSA. These results suggest that the lack of NDPS nephrotoxicity observed in
      Gunn rats is due to the deficiency in UDPGT in this strain rather than the parent
      Wistar strain being inherently nonresponsive to NDPS nephrotoxicity. Therefore,
      it appears that glucuronide metabolite(s) of NDHS and/or NDHSA contribute(s) to
      NDPS nephrotoxicity, although the exact nature of the nephrotoxicant glucuronide
      metabolite(s) of NDPS remains to be determined.

PMID- 9925802
TI  - Heavy metals mercury, cadmium, and chromium inhibit the activity of the mammalian
      liver and kidney sulfate transporter sat-1.
AB  - Heavy metal intoxication leads to defects in cellular uptake mechanisms in the
      mammalian liver and kidney. We have studied the effects of several heavy metals,
      including mercury, lead, cadmium, and chromium (at concentrations of 1 to 1000
      microM), on the activity of the mammalian sulfate transporter sat-1(2) in Xenopus
      oocytes. sat-1 encodes a sulfate/bicarbonate anion exchanger expressed in the rat
      liver and kidney. Mercury (10 microM) strongly inhibited sat-1 transport by
      reducing Vmax by eightfold but not its Km for inorganic sulfate (Si). Lead (up to
      1 mM) was unable to significantly inhibit sat-1 transporter activity. Cadmium
      (500 microM) showed weak inhibition of sat-1 transport by decreasing only sat-1
      Vmax. Chromium (100 microM) strongly inhibited sat-1 transport by reducing Km for
      Si by sevenfold, most probably by binding to the Si site, due to the strong
      structural similarity between the CrO2-4 and SO2-4 substrates. This study
      presents the first characterization of heavy metal inhibition of the hepatic and
      renal sulfate/bicarbonate transporter sat-1, through various mechanisms, which
      may lead to sulfaturia following heavy metal intoxication.

PMID- 9925803
TI  - In vitro estrogenicity of the catechol metabolites of selected polychlorinated
      biphenyls.
AB  - A considerable body of work has demonstrated that phenolic polychlorinated
      biphenyl (PCB) metabolites, structural analogues to estradiol, bind to the
      soluble estrogen receptor (ER) and that hydroxy PCB-ER complexes will translocate
      into the nucleus and bind to ER response elements in cultured cells. Although
      catechol estrogens exhibit weak estrogenic activity, the catechol PCB metabolites
      which are structurally similar to these ER agonists have gone untested for
      potential estrogenicity. In the present work we have assessed the estrogenicity
      of this second group of PCB metabolites, the catechols. The test compounds used
      in the present study were chosen to elucidate the effects of chlorine and
      catechol position on in vitro estrogenicity. Cultured HeLa cells, transfected
      with the estrogen reporter gene ERET81CAT and mouse ER cDNA, were incubated with
      PCB catechols. The cells were harvested at 28 h posttransfection and assayed for
      chloramphenicol acetyl transferase (CAT) activity. The responses elicited by the
      PCB catechols tested fell within the range of effect measured for the catechol
      estrogens and phenolic PCBs, and were within the range previously reported for
      other "environmental estrogens" such as nonylphenol and o,p'-DDT. Maximal
      measured responses were achieved at concentrations approximately two to three
      orders of magnitude higher than that of 17-beta-estradiol, indicating that PCB
      catechols have estrogenic activity in vitro. The extent of chlorination and the
      position of the catechol (3,4 vs 2,3 substitution) were important in determining
      estrogenicity in the compounds tested. The 2,3-catechol showed no detectable
      activity in this system, while activity of the 3, 4-catechols increased with the
      degree of chlorination. The observed estrogenicity of PCB catechols suggests that
      further oxidative metabolism of estrogenic PCB phenolic metabolites would not
      necessarily result in lowering the total estrogenic burden of a PCB-exposed
      organism. The present results imply that if estrogenic activity is assigned to an
      individual phenol, the potential contribution of its catechol metabolites to the
      total estrogenic burden should also be taken into consideration.

PMID- 9925804
TI  - Pyrrolizidine alkaloids crosslink DNA with actin.
AB  - Pyrrolizidine alkaloids (PAs) are toxic constituents of hundreds of plant
      species, some of which people are exposed to in herbal products and traditional
      remedies. The bioactivity of PAs are related, at least in part, to their ability
      to form DNA-protein complexes (DPC). Previous studies from our laboratory
      indicated a possible role for actin in PA-induced DPCs. Nuclei prepared from
      Madin-Darby bovine kidney (MDBK) and human breast carcinoma (MCF-7) cells were
      treated with the pyrrolic PAs dehydrosenecionine (DHSN) and dehydromonocrotaline
      (DHMO). DPCs were purified and then analyzed by Western immunoblotting. Actin was
      found in DPCs induced by both DHSN and DHMO, but not in those from control
      nuclei. Actin was also present in DPCs induced by cisplatinum and mitomycin C,
      two bifunctional cross-linkers. In separate experiments, DHSN and DHMO were
      crosslinked to a mixture of HindIII digested lambda phage with varying amounts of
      glutathione (GSH), cysteine, or methionine to identify the stoichiometry of
      competition between DNA and alternate nucleophiles for crosslink formation with
      pyrroles. GSH and cysteine, but not methionine, competed with lambda phage for
      DNA crosslinking, indicating that reduced thiols may have a role in nucleophilic
      reactions with pyrroles in the cell. While actin involvement in cisplatinum
      induced DPCs is documented, the discovery of actin crosslinking in PA or
      mitomycin C-treated cells or nuclei is, to our knowledge, novel. Pyrrole-induced
      DPC formation with actin, a protein with structural and/or regulatory importance
      proteins, may be a significant mechanism for PA toxicity and bioactivity.

PMID- 9925805
TI  - The dynamics of infinitesimally rare alleles, applied to the evolution of
      mutation rates and the expression of deleterious mutations.
AB  - A new method is presented for analysing the dynamics of a classical model where
      infinitesimally rare alleles segregate at an infinite number of unlinked loci,
      and where the alleles at different loci have equivalent effects. The dynamics of
      the distribution of the number of rare alleles per individual (the "phenotypic
      distribution") can be followed without knowing the frequencies of individual
      genotypes. Meiosis and random union of gametes have a very simple effect on the
      factorial cumulants of the phenotypic distribution which are consequently the
      natural set of variables to follow. An exact solution is presented for the
      dynamics of rare alleles under mutation and multiplicative selection. This
      solution has a simple representation in terms of the factorial cumulants. Unlike
      the QLE (quasi-linkage equilibrium) solution, this solution applies even when the
      population is far from linkage equilibrium. This approach is extended to analyse
      the joint dynamics of infinitesimally rare alleles at an infinite number of
      unlinked loci, together with a locus (with arbitrary allele frequencies) with
      which they interact. This more general method is used to investigate (1) the
      joint dynamics of a modifier of the mutation rate, together with deleterious
      alleles under mutation and multiplicative selection, and (2) the fate of an
      allele that ameliorates or exacerbates the fitness effects of deleterious
      alleles. When a new modifier allele causes a large change in the mutation rate,
      strong linkage disequilibrium is generated during its progress. However, using
      this new approach based on factorial cumulants, it is found that a remarkably
      simple invasion condition applies to alleles at the modifier locus, even when
      strong linkage disequilibrium is generated.

PMID- 9925806
TI  - Dispersal-induced instabilities in host-parasitoid metapopulations.
AB  - We present a general host-parasitoid metapopulation model and, using analytical
      techniques (supported by numerical simulations), investigate the effects of
      dispersal on the equilibrium stability of local populations. As has been
      demonstrated previously, if the intrinsic dynamics of local populations are
      unstable, then passive dispersal cannot stabilise. Extreme asymmetry in the
      dispersal fractions between the two species can, however, destabilise the
      metapopulation equilibrium state. Our key conclusion is that the precise effects
      of dispersal on stability depend critically on the underlying ecology of the
      interaction within each population. The presence of regulatory mechanisms, be
      they in the form of density-dependent host reproduction or the presence of host
      refugia, decreases the likelihood of observing dispersal-induced instabilities.
      Indeed, if the stabilising effects are sufficiently strong, then dispersal cannot
      be destabilising, no matter how asymmetric the dispersal fractions are. On the
      other hand, positive feedbacks arising from threshold effects in host
      reproduction or inversely density-dependent patterns of parasitism (due to, for
      example, long handling times or egg limitation) amplify the destabilising effects
      of dispersal.

PMID- 9925807
TI  - Genetic variability in sensitivity to population density affects the dynamics of
      simple ecological models.
AB  - Many 1-dimensional discrete time ecological models contain a sensitivity
      parameter that does not affect the dynamic complexity of these models. We show
      that genetic variability in this parameter can have a strong effect on population
      dynamics. We incorporate ecological dynamics in two different population genetic
      models with one locus and two alleles. The first is the classical model of a
      randomly mating population in Hardy-Weinberg equilibrium, and the second is a
      model of differential selection in males and females. In populations in Hardy
      Weinberg equilibrium, variability in the sensitivity parameter can be maintained
      by overdominance. In this case, the dynamics of the polymorphic population tend
      to be much simpler than those of monomorphic populations. In the model with
      different selection in males and females, polymorphisms can be maintained in
      various ways, e.g., by opposing directional selection in males and females.
      Polymorphism in the sensitivity parameter tends to simplify population dynamics
      in the model with different selection in males and females as well. A number of
      interesting dynamic effects can be observed, e.g., multiple attractors with
      complicated basins of attraction. Then the final state of the system after a
      successful invasion by mutant alleles may depend on the mutation rate and on the
      distribution of mutational steps. In addition, there are situations in which
      genetic variability destabilizes a stable population dynamic equilibrium in the
      monomorphic model. There is an analogy between genetic variability and
      variability imposed by the environment. If differences in sensitivity are caused
      by the environment, dynamic effects similar to those in the genetic models can be
      observed. In addition, source-sink structures that are known to occur in
      spatially structured models can be seen in the genetic model if one of the
      genotypes is inviable. The results suggest that combining ecological and
      population genetic models can lead to a number of new insights. More work is
      needed, e.g., with fertility models, in which fitnesses are not assigned to
      individuals, but to mating pairs.

PMID- 9925808
TI  - Modelling the integration of a transgene by stocking.
AB  - Simple models for the integration of a selectively neutral transgene into a feral
      population, by stocking of transgenic individuals, are developed. The impact of
      stocking individuals having multiple unlinked homozygous locations of the
      transgene is quantified. Initially it is assumed that there is no overlap between
      successive generations but a more general model for species having discrete
      overlapping generations is also developed. The primary application for this work
      is biological control. It is found that the integration of a transgene is
      considerably quickened by stocked transgenics carrying the transgene at multiple
      sites.

PMID- 9925809
TI  - Numerically exploring habitat fragmentation effects on populations using cell
      based coupled map lattices.
AB  - We examine habitat size, shape, and arrangement effects on populations using a
      discrete reaction-diffusion model. Diffusion is modeled passively and applied to
      a cellular grid of territories forming a coupled map lattice. Dispersal mortality
      is proportional to the amount of nonhabitat and fully occupied habitat
      surrounding a given cell, with distance decay. After verifying that our model
      produces the results expected for single patches of uniform habitat, we
      investigate heterogeneous and fragmented model landscapes. In heterogeneous
      single-patch systems near critical patch size, populations approach Gaussian
      spatial distributions with total population constrained by the capacity of the
      most limiting cell. In fragmented habitat landscapes, threshold effects are more
      complex and parametrically sensitive. The results from our experiments suggest
      the following: the ability to achieve persistence in hyperdispersed patchy
      habitats by adding similarly fragmented patches requires meeting threshold
      reproduction rates; persistent metapopulations in which no local population is
      individually persistent appear when dispersal distances and reproduction rates
      are both high, but only within narrow parameter ranges that are close to
      extinction thresholds; successful use of stepping-stone patches to support
      metapopulation systems appears unlikely for passively diffusing species;
      elongated patches offer early colonization advantages, but blocky patches offer
      greater population resilience near extinction thresholds. A common theme running
      through our findings is that population viability estimates may depend on our
      ability to determine when population and habitat systems are approaching
      extinction threshold conditions.

PMID- 9925810
TI  - Sexual selection by male choice in monogamous and polygynous human populations.
AB  - The theoretical possibility of coevolution of a viability-reducing female
      physical trait and a male mating preference for that trait by Fisherian sexual
      selection in monogamous and polygynous populations is demonstrated using two
      locus haploid models. It is assumed that there is dichotomous variation in male
      resources, resource-rich males have a wider choice among females than resource
      poor males, and a female has greater reproductive success when mated with a
      resource-rich male than a resource-poor one. Under these assumptions, we find
      that sexual selection operates effectively when female reproductive success is
      strongly dependent on male resource, the proportion of females that mate with
      resource-rich males is neither small nor large, the degree of polygyny is low,
      and resources are inherited from father to son. We suggest that some human female
      physical traits may have evolved by sexual selection through male choice. The
      evolution of skin color by sexual selection is discussed as an example.

PMID- 9925811
TI  - Dynamics of co-infection with M. Tuberculosis and HIV-1.
AB  - Since 1985, there has been a renewed epidemic of tuberculosis (TB) that was
      previously thought to be in check. There is evidence to believe the main factor
      for this resurgence has been the human immunodeficiency virus (HIV). Co-infection
      with HIV and M. Tuberculosis has profound implications for the course of both
      diseases. This study represents a first attempt to understand how the
      introduction of an opportunistic infection, namely Mycobacterium tuberculosis,
      the bacteria that causes TB, affects the dynamic interaction of HIV-1 and the
      immune system. We create a mathematical model using ordinary differential
      equations to describe the interaction of HIV and TB with the immune system. It is
      known that infection with TB can decrease the CD4(+) T cell counts-a key marker
      of AIDS progression; thus, it shortens survival in HIV infected individuals.
      Another main marker for HIV progression is the viral load. If this load is
      increased due to the presence of opportunistic infections, the disease
      progression is much more rapid. We also explore the effects of drug treatment on
      the TB infection in the doubly-infected patient.

PMID- 9925812
TI  - Volume 249, Number 2 (1998), in Article No. VY989337, "The C Terminus of E1A
      Regulates Tumor Progression and Epithelial Cell Differentiation," by Robert S.
      Fischer and Margaret P. Quinlan, pages 427-439:

PMID- 9925814
TI  - Perspectives on ion channel assembly 

PMID- 9925813
TI  - The 52nd annual meeting and symposium of the Society of General Physiologists.
      Local calcium signaling in cell physiology.

PMID- 9925815
TI  - Ion channel assembly: creating structures that function.

PMID- 9925816
TI  - Determinants responsible for assembly of the nicotinic acetylcholine receptor.

PMID- 9925817
TI  - Unitary Ca2+ current through cardiac ryanodine receptor channels under quasi
      physiological ionic conditions.
AB  - Single canine cardiac ryanodine receptor channels were incorporated into planar
      lipid bilayers. Single-channel currents were sampled at 1-5 kHz and filtered at
      0.2-1.0 kHz. Channel incorporations were obtained in symmetrical solutions (20 mM
      HEPES-Tris, pH 7.4, and pCa 5). Unitary Ca2+ currents were monitored when 2-30 mM
      Ca2+ was added to the lumenal side of the channel. The relationship between the
      amplitude of unitary Ca2+ current (at 0 mV holding potential) and lumenal [Ca2+]
      was hyperbolic and saturated at approximately 4 pA. This relationship was then
      defined in the presence of different symmetrical CsCH3SO3 concentrations (5, 50,
      and 150 mM). Under these conditions, unitary current amplitude was 1.2 +/- 0.1,
      0.65 +/- 0.1, and 0.35 +/- 0.1 pA in 2 mM lumenal Ca2+; and 3.3 +/- 0.4, 2.4 +/-
      0. 2, and 1.63 +/- 0.2 pA in 10 mM lumenal Ca2+ (n > 6). Unitary Ca2+ current was
      also defined in the presence of symmetrical [Mg2+] (1 mM) and low [Cs+] (5 mM).
      Under these conditions, unitary Ca2+ current in 2 and 10 mM lumenal Ca2+ was 0.66
      +/- 0.1 and 1.52 +/- 0.06 pA, respectively. In the presence of higher symmetrical
      [Cs+] (50 mM), Mg2+ (1 mM), and lumenal [Ca2+] (10 mM), unitary Ca2+ current
      exhibited an amplitude of 0.9 +/- 0.2 pA (n = 3). This result indicates that the
      actions of Cs+ and Mg2+ on unitary Ca2+ current were additive. These data
      demonstrate that physiological levels of monovalent cation and Mg2+ effectively
      compete with Ca2+ as charge carrier in cardiac ryanodine receptor channels. If
      lumenal free Ca2+ is 2 mM, then our results indicate that unitary Ca2+ current
      under physiological conditions should be <0.6 pA.

PMID- 9925818
TI  - Time course of individual Ca2+ sparks in frog skeletal muscle recorded at high
      time resolution.
AB  - Discrete Ca2+ release events (Ca2+ "sparks") were recorded in cut segments of
      single frog skeletal muscle fibers using a video-rate laser-scanning confocal
      microscope operating in line-scan mode (63 microseconds per line). Fibers loaded
      with the Ca2+ indicator fluo-3 were voltage clamped at a holding potential of 0
      mV, briefly reprimed at -90 mV, and then strongly depolarized with a large test
      pulse to activate any reprimed voltage sensors. Using this high time resolution
      system, it was possible to record individual Ca2+ sparks at approximately 30-fold
      higher time resolution than previously attained. The resulting new experimental
      data provides a means of characterizing the time course of fluorescence during
      the brief (a few milliseconds) rising phase of a spark, which was not possible
      with the previously used 1.5-2 ms per line confocal systems. Analysis of the time
      course of individual identified events indicates that fluorescence begins to rise
      rather abruptly at the start of the spark, continues to rise at a slightly
      decreasing rate to a relatively sharp peak, and then declines along a quasi
      exponential time course. The mean rise time of 198 sparks was 4.7 +/- 0.1 ms, and
      there was no correlation between rise time and peak amplitude. Average sparks
      constructed by temporally and spatially superimposing and summing groups of
      individual sparks having similar rise times gave a lower noise representation of
      the sparks, consistent with the time course of individual events. In theory, the
      rising phase of a spark provides a lower bound estimation of the time that Ca2+
      ions are being released by the sarcoplasmic reticulum Ca2+ channel(s) generating
      the spark. The observed time course of fluorescence suggests that the Ca2+
      release underlying a spark could continue at a fairly constant rate throughout
      the rising phase of the spark, and then stop rather abruptly at the time of the
      peak.

PMID- 9925819
TI  - Radial localization of inositol 1,4,5-trisphosphate-sensitive Ca2+ release sites
      in Xenopus oocytes resolved by axial confocal linescan imaging.
AB  - The radial localization and properties of elementary calcium release events
      ("puffs") were studied in Xenopus oocytes using a confocal microscope equipped
      with a piezoelectric focussing unit to allow rapid (>100 Hz) imaging of calcium
      signals along a radial line into the cell with a spatial resolution of <0.7
      micrometer. Weak photorelease of caged inositol 1,4,5-trisphosphate (InsP3)
      evoked puffs arising predominantly within a 6-micrometer thick band located
      within a few micrometers of the cell surface. Approximately 25% of puffs had a
      restricted radial spread, consistent with calcium release from a single site.
      Most puffs, however, exhibited a greater radial spread (3.25 micrometer), likely
      involving recruitment of radially neighboring release sites. Calcium waves evoked
      by just suprathreshold stimuli exhibited radial calcium distributions consistent
      with inward diffusion of calcium liberated at puff sites, whereas stronger
      flashes evoked strong, short-latency signals at depths inward from puff sites,
      indicating deep InsP3-sensitive stores activated at higher concentrations of
      InsP3. Immunolocalization of InsP3 receptors showed punctate staining throughout
      a region corresponding to the localization of puffs and subplasmalemmal
      endoplasmic reticulum. The radial organization of puff sites a few micrometers
      inward from the plasma membrane may have important consequences for activation of
      calcium-dependent ion channels and "capacitative" calcium influx. However, on the
      macroscopic (hundreds of micrometers) scale of global calcium waves, release can
      be considered to occur primarily within a thin, essentially two-dimensional
      subplasmalemmal shell.

PMID- 9925820
TI  - The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and
      spontaneous transient outward currents in single smooth muscle cells.
AB  - Localized, transient elevations in cytosolic Ca2+, known as Ca2+ sparks, caused
      by Ca2+ release from sarcoplasmic reticulum, are thought to trigger the opening
      of large conductance Ca2+-activated potassium channels in the plasma membrane
      resulting in spontaneous transient outward currents (STOCs) in smooth muscle
      cells. But the precise relationships between Ca2+ concentration within the
      sarcoplasmic reticulum and a Ca2+ spark and that between a Ca2+ spark and a STOC
      are not well defined or fully understood. To address these problems, we have
      employed two approaches using single patch-clamped smooth muscle cells freshly
      dissociated from toad stomach: a high speed, wide-field imaging system to
      simultaneously record Ca2+ sparks and STOCs, and a method to simultaneously
      measure free global Ca2+ concentration in the sarcoplasmic reticulum ([Ca2+]SR)
      and in the cytosol ([Ca2+]CYTO) along with STOCs. At a holding potential of 0 mV,
      cells displayed Ca2+ sparks and STOCs. Ca2+ sparks were associated with STOCs;
      the onset of the sparks coincided with the upstroke of STOCs, and both had
      approximately the same decay time. The mean increase in [Ca2+]CYTO at the time
      and location of the spark peak was approximately 100 nM above a resting
      concentration of approximately 100 nM. The frequency and amplitude of spontaneous
      Ca2+ sparks recorded at -80 mV were unchanged for a period of 10 min after
      removal of extracellular Ca2+ (nominally Ca2+-free solution with 50 microM EGTA),
      indicating that Ca2+ influx is not necessary for Ca2+sparks. A brief pulse of
      caffeine (20 mM) elicited a rapid decrease in [Ca2+]SR in association with a
      surge in [Ca2+]CYTO and a fusion of STOCs, followed by a fast restoration of
      [Ca2+]CYTO and a gradual recovery of [Ca2+]SR and STOCs. The return of global
      [Ca2+]CYTO to rest was an order of magnitude faster than the refilling of the
      sarcoplasmic reticulum with Ca2+. After the global [Ca2+]CYTO was fully restored,
      recovery of STOC frequency and amplitude were correlated with the level of
      [Ca2+]SR, even though the time for refilling varied greatly. STOC frequency did
      not recover substantially until the [Ca2+]SR was restored to 60% or more of
      resting levels. At [Ca2+]SR levels above 80% of rest, there was a steep
      relationship between [Ca2+]SR and STOC frequency. In contrast, the relationship
      between [Ca2+]SR and STOC amplitude was linear. The relationship between [Ca2+]SR
      and the frequency and amplitude was the same for Ca2+ sparks as it was for STOCs.
      The results of this study suggest that the regulation of [Ca2+]SR might provide
      one mechanism whereby agents could govern Ca2+ sparks and STOCs. The relationship
      between Ca2+ sparks and STOCs also implies a close association between a
      sarcoplasmic reticulum Ca2+ release site and the Ca2+-activated potassium
      channels responsible for a STOC.

PMID- 9925821
TI  - Functional coupling of ryanodine receptors to KCa channels in smooth muscle cells
      from rat cerebral arteries.
AB  - The relationship between Ca2+ release ("Ca2+ sparks") through ryanodine-sensitive
      Ca2+ release channels in the sarcoplasmic reticulum and KCa channels was examined
      in smooth muscle cells from rat cerebral arteries. Whole cell potassium currents
      at physiological membrane potentials (-40 mV) and intracellular Ca2+ were
      measured simultaneously, using the perforated patch clamp technique and a laser
      two-dimensional (x-y) scanning confocal microscope and the fluorescent Ca2+
      indicator, fluo-3. Virtually all (96%) detectable Ca2+ sparks were associated
      with the activation of a spontaneous transient outward current (STOC) through KCa
      channels. A small number of sparks (5 of 128) were associated with currents
      smaller than 6 pA (mean amplitude, 4.7 pA, at -40 mV). Approximately 41% of STOCs
      occurred without a detectable Ca2+ spark. The amplitudes of the Ca2+ sparks
      correlated with the amplitudes of the STOCs (regression coefficient 0.8; P <
      0.05). The half time of decay of Ca2+ sparks (56 ms) was longer than the
      associated STOCs (9 ms). The mean amplitude of the STOCs, which were associated
      with Ca2+ sparks, was 33 pA at -40 mV. The mean amplitude of the "sparkless"
      STOCs was smaller, 16 pA. The very significant increase in KCa channel open
      probability (>10(4)-fold) during a Ca2+ spark is consistent with local Ca2+
      during a spark being in the order of 1-100 microM. Therefore, the increase in
      fractional fluorescence (F/Fo) measured during a Ca2+ spark (mean 2.04 F/Fo or
      approximately 310 nM Ca2+) appears to significantly underestimate the local Ca2+
      that activates KCa channels. These results indicate that the majority of
      ryanodine receptors that cause Ca2+ sparks are functionally coupled to KCa
      channels in the surface membrane, providing direct support for the idea that Ca2+
      sparks cause STOCs.

PMID- 9925822
TI  - Active nuclear import and export is independent of lumenal Ca2+ stores in intact
      mammalian cells.
AB  - The nuclear pore complex (NPC) mediates communication between the cytoplasm and
      nucleus in eukaryotic cells. Active transport of large polypeptides as well as
      passive diffusion of smaller (approximately 10 kD) macromolecules through the NPC
      can be inhibited by depletion of intracellular Ca2+ stores. However, the
      physiological relevance of this process for the regulation of nucleocytoplasmic
      trafficking is not yet clear. We expressed green fluorescent protein (GFP)-tagged
      glucocorticoid receptor (GR) and mitogen-activated protein (MAP) kinase-activated
      protein kinase 2 (MK2) to study the effect of Ca2+ store depletion on active
      transport in HM1 cells, a human embryonic kidney cell line stably transfected
      with the muscarinic M1 receptor. Dexamethasone-induced nuclear import of GR-GFP
      and anisomycin-induced nuclear export of GFP-MK2 was monitored by confocal
      microscopy. We found that store depletion by carbachol, thapsigargin or ionomycin
      had no effect on GR-GFP import, whereas pretreatment with 1,2-bis-(o
      aminophenoxy) ethane-N,N,N', N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM)
      attenuated import significantly. Export of GFP-MK2 was not influenced by any
      pretreatment. Moreover, carbachol stimulated GFP-MK2 translocation to the
      cytoplasm in the absence of anisomycin. These results demonstrate that Ca2+ store
      depletion in intact HM1 cells is not directly linked to the inhibition of active
      protein transport through the NPC. The inhibition of GR-GFP import but not GFP
      MK2 export by BAPTA-AM presumably involves a depletion-independent mechanism that
      interferes with components of the nuclear import pathway.

PMID- 9925823
TI  - Reversible Ca gradients between the subplasmalemma and cytosol differentially
      activate Ca-dependent Cl currents.
AB  - Xenopus oocytes express several different Ca-activated Cl currents that have
      different waveforms and biophysical properties. We compared the stimulation of Ca
      activated Cl currents measured by two-microelectrode voltage clamp with the Ca
      transients measured in the same cell by confocal microscopy and Ca-sensitive
      fluorophores. The purpose was to determine how the amplitude and/or spatio
      temporal features of the Ca signal might explain how these different Cl currents
      were activated by Ca. Because Ca release from stores was voltage independent,
      whereas Ca influx depended upon the electrochemical driving force, we were able
      to separately assess the contribution of Ca from these two sources. We were
      surprised to find that Ca signals measured with a cytosolic Ca-sensitive dye,
      dextran-conjugated Ca-green-1, correlated poorly with Cl currents. This suggested
      that Cl channels located at the plasma membrane and the Ca-sensitive dye located
      in the bulk cytosol were sensing different [Ca]. This was true despite Ca
      measurement in a confocal slice very close to the plasma membrane. In contrast, a
      membrane-targeted Ca-sensitive dye (Ca-green-C18) reported a Ca signal that
      correlated much more closely with the Cl currents. We hypothesize that very
      local, transient, reversible Ca gradients develop between the subplasmalemmal
      space and the bulk cytosol. [Ca] is higher near the plasma membrane when Ca is
      provided by Ca influx, whereas the gradient is reversed when Ca is released from
      stores, because Ca efflux across the plasma membrane is faster than diffusion of
      Ca from the bulk cytosol to the subplasmalemmal space. Because dissipation of the
      gradients is accelerated by inhibition of Ca sequestration into the endoplasmic
      reticulum with thapsigargin, we conclude that [Ca] in the bulk cytosol declines
      slowly partly due to futile recycling of Ca through the endoplasmic reticulum.

PMID- 9925824
TI  - Light-dependent changes in outer segment free-Ca2+ concentration in salamander
      cone photoreceptors.
AB  - Simultaneous measurements of photocurrent and outer segment Ca2+ were made from
      isolated salamander cone photoreceptors. While recording the photocurrent from
      the inner segment, which was drawn into a suction pipette, a laser spot confocal
      technique was employed to evoke fluorescence from the outer segment of a cone
      loaded with the Ca2+ indicator fluo-3. When a dark-adapted cone was exposed to
      the intense illumination of the laser, the circulating current was completely
      suppressed and fluo-3 fluorescence rapidly declined. In the more numerous red
      sensitive cones this light-induced decay in fluo-3 fluorescence was best fitted
      as the sum of two decaying exponentials with time constants of 43 +/- 2.4 and 640
      +/- 55 ms (mean +/- SEM, n = 25) and unequal amplitudes: the faster component was
      1.7-fold larger than the slower. In blue-sensitive cones, the decay in
      fluorescence was slower, with time constants of 140 +/- 30 and 1,400 +/- 300 ms,
      and nearly equal amplitudes. Calibration of fluo-3 fluorescence in situ from red
      sensitive cones allowed the calculation of the free-Ca2+ concentration, yielding
      values of 410 +/- 37 nM in the dark-adapted outer segment and 5.5 +/- 2.4 nM
      after saturating illumination (mean +/- SEM, n = 8). Photopigment bleaching by
      the laser resulted in a considerable reduction in light sensitivity and a
      maintained decrease in outer segment Ca2+ concentration. When the photopigment
      was regenerated by applying exogenous 11-cis-retinal, both the light sensitivity
      and fluo-3 fluorescence recovered rapidly to near dark-adapted levels.
      Regeneration of the photopigment allowed repeated measurements of fluo-3
      fluorescence to be made from a single red-sensitive cone during adaptation to
      steady light over a range of intensities. These measurements demonstrated that
      the outer segment Ca2+ concentration declines in a graded manner during
      adaptation to background light, varying linearly with the magnitude of the
      circulating current.

PMID- 9925825
TI  - Block of brain sodium channels by peptide mimetics of the isoleucine,
      phenylalanine, and methionine (IFM) motif from the inactivation gate.
AB  - Inactivation of sodium channels is thought to be mediated by an inactivation gate
      formed by the intracellular loop connecting domains III and IV. A hydrophobic
      motif containing the amino acid sequence isoleucine, phenylalanine, and
      methionine (IFM) is required for the inactivation process. Peptides containing
      the IFM motif, when applied to the cytoplasmic side of these channels, produce
      two types of block: fast block, which resembles the inactivation process, and
      slow, use-dependent block stimulated by strong depolarizing pulses. Fast block by
      the peptide ac-KIFMK-NH2, measured on sodium channels whose inactivation was
      slowed by the alpha-scorpion toxin from Leiurus quinquestriatus (LqTx), was
      reversed with a time constant of 0.9 ms upon repolarization. In contrast, control
      and LqTx-modified sodium channels were slower to recover from use-dependent
      block. For fast block, linear peptides of three to six amino acid residues
      containing the IFM motif and two positive charges were more effective than
      peptides with one positive charge, whereas uncharged IFM peptides were
      ineffective. Substitution of the IFM residues in the peptide ac-KIFMK-NH2 with
      smaller, less hydrophobic residues prevented fast block. The positively charged
      tripeptide IFM-NH2 did not cause appreciable fast block, but the divalent cation
      IFM-NH(CH2)2NH2 was as effective as the pentapeptide ac-KIFMK-NH2. The
      constrained peptide cyclic KIFMK containing two positive charges did not cause
      fast block. These results indicate that the position of the positive charges is
      unimportant, but flexibility or conformation of the IFM-containing peptide is
      important to allow fast block. Slow, use-dependent block was observed with IFM
      containing peptides of three to six residues having one or two positive charges,
      but not with dipeptides or phenylalanine-amide. In contrast to its lack of fast
      block, cyclic KIFMK was an effective use-dependent blocker. Substitutions of
      amino acid residues in the tripeptide IFM-NH2 showed that large hydrophobic
      residues are preferred in all three positions for slow, use-dependent block.
      However, substitution of the large hydrophobic residue diphenylalanine or the
      constrained residues phenylglycine or tetrahydroisoquinoline for phe decreased
      potency, suggesting that this phe residue must be able to enter a restricted
      hydrophobic pocket during the binding of IFM peptides. Together, the results on
      fast block and slow, use-dependent block indicate that IFM peptides form two
      distinct complexes of different stability and structural specificity with
      receptor site(s) on the sodium channel. It is proposed that fast block represents
      binding of these peptides to the inactivation gate receptor, while slow, use
      dependent block represents deeper binding of the IFM peptides in the pore.

PMID- 9925826
TI  - Simultaneous binding of basic peptides at intracellular sites on a large
      conductance Ca2+-activated K+ channel. Equilibrium and kinetic basis of
      negatively coupled ligand interactions.
AB  - The homologous Kunitz inhibitor proteins, bovine pancreatic trypsin inhibitor
      (BPTI) and dendrotoxin I (DTX-I), interact with large conductance Ca2+-activated
      K+ channels (maxi-KCa) by binding to an intracellular site outside of the pore to
      produce discrete substate events. In contrast, certain homologues of the Shaker
      ball peptide produce discrete blocking events by binding within the ion
      conduction pathway. In this study, we investigated ligand interactions of these
      positively charged peptide molecules by analysis of single maxi-KCa channels in
      planar bilayers recorded in the presence of DTX-I and BPTI, or DTX-I and a high
      affinity homologue of ball peptide. Both DTX-I (Kd, 16.5 nM) and BPTI (Kd, 1, 490
      nM) exhibit one-site binding kinetics when studied alone; however, records in the
      presence of DTX-I plus BPTI demonstrate simultaneous binding of these two
      molecules. The affinity of BPTI (net charge, +6) decreases by 11.7-fold (Kd,
      17,500 nM) when DTX-I (net charge, +10) is bound and, conversely, the affinity of
      DTX-I decreases by 10.8-fold (Kd, 178 nM) when BPTI is bound. The ball peptide
      homologue (BP; net charge, +6) exhibits high blocking affinity (Kd, 7.2 nM) at a
      single site when studied alone, but has 8.0-fold lower affinity (Kd, 57 nM) for
      blocking the DTX-occupied channel. The affinity of DTX-I likewise decreases by
      8.4-fold (Kd, 139 nM) when BP is bound. These results identify two types of
      negatively coupled ligand-ligand interactions at distinct sites on the
      intracellular surface of maxi-KCa channels. Such antagonistic ligand interactions
      explain how the binding of BPTI or DTX-I to four potentially available sites on a
      tetrameric channel protein can exhibit apparent one-site kinetics. We hypothesize
      that negatively coupled binding equilibria and asymmetric changes in transition
      state energies for the interaction between DTX-I and BP originate from repulsive
      electrostatic interactions between positively charged peptide ligands on the
      channel surface. In contrast, there is no detectable binding interaction between
      DTX-I on the inside and tetraethylammonium or charybdotoxin on the outside of the
      maxi-KCa channel.

PMID- 9925827
TI  - Interaction between the pore and a fast gate of the cardiac sodium channel.
AB  - Permeant ions affect a fast gating process observed in human cardiac sodium
      channels (Townsend, C., H.A. Hartmann, and R. Horn. 1997. J. Gen. Physiol. 110:11
      21). Removal of extracellular permeant ions causes a reduction of open
      probability at positive membrane potentials. These results suggest an intimate
      relationship between the ion-conducting pore and the gates of the channel. We
      tested this hypothesis by three sets of manipulations designed to affect the
      binding of cations within the pore: application of intracellular pore blockers,
      mutagenesis of residues known to contribute to permeation, and chemical
      modification of a native cysteine residue (C373) near the extracellular mouth of
      the pore. The coupling between extracellular permeant ions and this fast gating
      process is abolished both by pore blockers and by a mutation that severely
      affects selectivity. A more superficial pore mutation or chemical modification of
      C373 reduces single channel conductance while preserving both selectivity of the
      pore and the modulatory effects of extracellular cations. Our results demonstrate
      a modulatory gating role for a region deep within the pore and suggest that the
      structure of the permeation pathway is largely preserved when a channel is
      closed.

PMID- 9925830
TI  - ACKNOWLEDGMENT. The editors thank the following for their valuable contributions
      as reviewers for the journal of general physiology in 1998 

PMID- 9925828
TI  - Augmentation of recovery from inactivation by site-3 Na channel toxins. A single
      channel and whole-cell study of persistent currents.
AB  - Site-3 toxins isolated from several species of scorpion and sea anemone bind to
      voltage-gated Na channels and prolong the time course of INa by interfering with
      inactivation with little or no effect on activation, effects that have
      similarities to those produced by genetic diseases in skeletal muscle (myotonias
      and periodic paralysis) and heart (long QT syndrome). Some published reports have
      also reported the presence of a noninactivating persistent current in site-3
      toxin-treated cells. We have used the high affinity site-3 toxin Anthopleurin B
      to study the kinetics of this current and to evaluate kinetic differences between
      cardiac (in RT4-B8 cells) and neuronal (in N1E-115 cells) Na channels. By reverse
      transcription-PCR from N1E-115 cell RNA multiple Na channel transcripts were
      detected; most often isolated were sequences homologous to rBrII, although at low
      frequency sequences homologous to rPN1 and rBrIII were also detected. Toxin
      treatment induced a voltage-dependent plateau current in both isoforms for which
      the relative amplitude (plateau current/peak current) approached a constant value
      with depolarization, although the magnitude was much greater for neuronal (17%)
      than cardiac (5%) INa. Cell-attached patch recordings revealed distinct
      quantitative differences in open times and burst durations between isoforms, but
      for both isoforms the plateau current comprised discrete bursts separated by
      quiescent periods, consistent with toxin induction of an increase in the rate of
      recovery from inactivation rather than a modal failure of inactivation. In accord
      with this hypothesis, toxin increased the rate of whole-cell recovery at all
      tested voltages. Moreover, experimental data support a model whereby recovery at
      negative voltages is augmented through closed states rather than through the open
      state. We conclude that site-3 toxins produce qualitatively similar effects in
      cardiac and neuronal channels and discuss implications for channel kinetics.

PMID- 9925829
TI  - Functional consequences of a decreased potassium affinity in a potassium channel
      pore. Ion interactions and C-type inactivation.
AB  - Ions bound near the external mouth of the potassium channel pore impede the C
      type inactivation conformational change (Lopez-Barneo, J., T. Hoshi, S.
      Heinemann, and R. Aldrich. 1993. Receptors Channels. 1:61- 71; Baukrowitz, T.,
      and G. Yellen. 1995. Neuron. 15:951-960). In this study, we present evidence that
      the occupancy of the C-type inactivation modulatory site by permeant ions is not
      solely dependent on its intrinsic affinity, but is also a function of the
      relative affinities of the neighboring sites in the potassium channel pore. The
      A463C mutation in the S6 region of Shaker decreases the affinity of an internal
      ion binding site in the pore (Ogielska, E.M., and R.W. Aldrich, 1998). However,
      we have found that this mutation also decreases the C-type inactivation rate of
      the channel. Our studies indicate that the C-type inactivation effects observed
      with substitutions at position A463 most likely result from changes in the pore
      occupancy of the channel, rather than a change in the C-type inactivation
      conformational change. We have found that a decrease in the potassium affinity of
      the internal ion binding site in the pore results in lowered (electrostatic)
      interactions among ions in the pore and as a result prolongs the time an ion
      remains bound at the external C-type inactivation site. We also present evidence
      that the C-type inactivation constriction is quite local and does not involve a
      general collapse of the selectivity filter. Our data indicate that in A463C
      potassium can bind within the selectivity filter without interfering with the
      process of C-type inactivation.

PMID- 9925831
TI  - Parents, physicians, and antibiotic use.
AB  - BACKGROUND: Emergence of resistant bacterial pathogens has increased concerns
      about antibiotic prescribing patterns. Parent expectations and pressure may
      influence these patterns. OBJECTIVE: To understand how parents influence the
      prescribing patterns of physicians and what strategies physicians believe are
      important if we are going to reduce inappropriate use of oral antimicrobial
      agents. DESIGNS AND METHODS: One thousand pediatricians who are members of the
      American Academy of Pediatrics were asked to complete a semi-structured
      questionnaire. The physicians were chosen randomly by the American Academy of
      Pediatrics. RESULTS: Nine hundred fifteen pediatricians were eligible and 610
      surveys were analyzable, for a response rate of 67%. The majority of respondents
      were male (56%), worked in a group practice (51%), saw an average of 114 patients
      per week and were in practice for 14 years. Forty percent of the pediatricians
      indicated that 10 or more times in the past month a parent had requested an
      antibiotic when the physician did not feel it was indicated. Forty-eight percent
      reported that parents always, most of the time, or often pressure them to
      prescribe antibiotics when their children are ill but antibiotics are not
      indicated. In follow-up questions, approximately one-third of physicians reported
      they occasionally or more frequently comply with these requests. Seventy-eight
      percent felt that educating parents would be the single most important program
      for reducing inappropriate oral antibiotic use and 54% indicated that parental
      pressure, in contrast to concerns about legal liability (12%) or need to be
      efficient in practice (19%), contributed most to inappropriate use of oral
      antibiotics. CONCLUSIONS: Pediatricians acknowledge prescribing antimicrobial
      agents when they are not indicated. Pediatricians believe educating parents is
      necessary to promote the judicious use of antimicrobial agents.

PMID- 9925832
TI  - Neurologic status of newborns with congenital heart defects before open heart
      surgery.
AB  - Controversy exists regarding the integrity of the nervous system in the newborn
      with a congenital heart defect who must undergo corrective or palliative open
      heart surgery. Neurodevelopmental sequelae have been primarily attributed to
      surgical procedures without standardized evaluation of the preoperative
      neurologic status. OBJECTIVE: To determine whether newborns with congenital heart
      defects demonstrate abnormalities in neurobehavioral status before surgery. STUDY
      DESIGN: In this prospective study, a standardized neonatal neurobehavioral
      assessment and a neurologic examination were conducted independently in a
      consecutive series of 56 neonates referred to our hospital for investigation of
      open heart surgery. RESULTS: Neurobehavioral and neurologic abnormalities were
      documented in greater than half of the cohort and included hypotonia, hypertonia,
      jitteriness, motor asymmetries, and absent suck. Poor state regulation (62%) and
      feeding difficulties (34%) also were commonly observed. Furthermore, 3 subjects
      had seizures, 35.7% were microcephalic, and 12.5% were macrocephalic. The overall
      likelihood of neurobehavioral abnormalities was not enhanced by indicators of
      cardiorespiratory compromise. Interestingly, newborns with acyanotic congenital
      heart defects were more likely to demonstrate neurologic compromise than were
      those with cyanotic defects. CONCLUSIONS: Findings suggest that the prevalence of
      neurobehavioral abnormalities before surgery in newborns with congenital heart
      defects has been underappreciated and would indicate that factors other than
      intraoperative procedures should be considered in the genesis of brain injury in
      this population.congenital heart defects, neurologic examination, newborn.

PMID- 9925833
TI  - Risk factors and course of illness among children with invasive penicillin
      resistant Streptococcus pneumoniae. The Streptococcus pneumoniae Working Group.
AB  - OBJECTIVES: To assess differences in risk factors, clinical presentation, and
      course of illness between children infected with penicillin-sensitive and drug
      resistant Streptococcus pneumoniae (DRSP). DESIGN: A retrospective cohort study
      conducted in Uruguay and Argentina using information from a hospital-based
      surveillance system. Hospitalized children 5 years of age and younger who had S
      pneumoniae isolated from a normally sterile site between June 1993 and October
      1996 were eligible. Hospital records were linked with surveillance data. Both
      stratified univariate analysis and logistic regression was completed. RESULTS: Of
      the 380 children eligible for the study, 274 records (72%) were available for
      review. Ninety-nine children (36%) had DRSP; 46 showed intermediate
      susceptibility (minimum inhibitory concentration, 0.12-1.0 microg/mL) and 53
      showed high-level resistance (minimum inhibitory concentration >/=2.0 microg/mL).
      Children with meningitis were less likely to have DRSP than those with other
      forms of invasive disease (relative risk = 0. 5; 95% confidence interval [CI],
      0.2-0.9). Risk factors associated with DRSP were use of penicillin or ampicillin
      in the 3 months before illness (odds ratio = 2.9; 95% CI, 1.5-5.7) and possession
      of private medical coverage (odds ratio = 2.4; 95% CI, 1.2-5.0). Response to
      therapy, including response to penicillin or ampicillin among children with
      nonmeningeal invasive disease, course of illness, and clinical outcome did not
      differ significantly between children infected with penicillin-susceptible or
      penicillin-resistant isolates. CONCLUSION: In this study, previous use of
      penicillin or ampicillin and private medical coverage were associated with having
      DRSP. Children with nonmeningeal invasive disease responded equally well to
      penicillin regardless of the penicillin susceptibility of their pneumococcal
      isolate.

PMID- 9925834
TI  - A multiple-dosing, placebo-controlled study of budesonide inhalation suspension
      given once or twice daily for treatment of persistent asthma in young children
      and infants.
AB  - RATIONALE: Topical antiinflammatory medications such as inhaled corticosteroids
      are recommended for therapy of asthma, but no formulation suitable for
      administration to infants and young children is available in the United States.
      METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel
      group study comparing the efficacy and safety of four dosing regimens of bude
      sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and
      children (64% boys), ages 6 months to 8 years, with moderate persistent asthma.
      Approximately 30% of children were previously on inhaled corticosteroids that
      were discontinued before the study. Active treatments were comprised of BIS 0.25
      mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy
      was assessed by twice daily recording at home of asthma symptom scores and use of
      rescue medication, and discontinuation from the study because of worsening asthma
      and/or a requirement for systemic steroids. Peak flow measurements were recorded
      twice daily on diary and spirometry was recorded at clinic visits for those
      children able to perform these tests. Safety was assessed by reported adverse
      events and by cortisol testing (adrenocorticotropic hormone stimulation) in a
      subset of patients. RESULTS: Patients enrolled had an average duration of asthma
      of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3).
      All dosing regimens with BIS produced statistically significant improvement in
      various clinical efficacy measures for asthma control compared with placebo. The
      lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters
      than seen with the other doses administered. Separation between active treatment
      and placebo in daytime and nighttime symptom scores were observed by week 2 of
      treatment for all BIS treatment regimens. A significant increase in peak flow
      measurement was observed in most active treatment groups compared with placebo in
      the subset of children able to do pulmonary function testing. All treatment
      groups showed numerical improvement in forced expiratory volume in 1 second but
      only the 0.5-mg BID dose was significantly different from placebo. Adverse events
      for the entire group and response to adrenocorticotropic hormone in a subgroup of
      children who underwent cortisol testing before and at the end of the treatment
      period were no different in budesonide-treated patients in comparison to placebo.
      CONCLUSION: Results of this study demonstrate that BIS is effective and safe for
      infants and young children with moderate persistent asthma in a multiple dose
      range, and that QD dosing is an important option to be considered by the
      prescribing physician.

PMID- 9925835
TI  - How does home management of asthma exacerbations by parents of inner-city
      children differ from NHLBI guideline recommendations? National Heart, Lung, and
      Blood Institute.
AB  - OBJECTIVES: 1) To describe the asthma morbidity, primary care practices, and
      asthma home management of inner-city children with asthma; 2) to determine the
      responses of parental caretakers to asthma exacerbations in their child; and 3)
      to compare these responses to the recommendations of the National Heart, Lung,
      and Blood Institute (NHLBI) asthma guidelines for home management of acute
      exacerbations of asthma. DESIGN AND METHODS: A 64-item telephone survey was
      administered between July 1996 and June 1997 to 220 parental caretakers of 2- to
      12-year-old children who had been hospitalized with asthma at an inner-city
      medical center from January, 1995 to February, 1996. Sociodemographics, primary
      care practices, asthma morbidity, and asthma home management were assessed.
      Parents were asked what they would do if their child "began wheezing and
      breathing faster than usual." RESULTS: Morbidity measures indicated that there
      were an average of 2.5 +/- 4.5 emergency department visits for asthma in the last
      6 months, 1.6 +/- 2.2 hospitalizations for asthma in the last 12 months, and 18.1
      +/- 17.9 asthma-related school absences in the previous school year. Most, but
      not all, of the families had primary care providers and most had phone access to
      them. Half of the families (51%) reported having been given a written asthma
      action plan. Only 30% of families with children age 5 years and older had peak
      flow meters. In contrast, almost all families (97%) had equipment for inhalation
      of beta-agonists. Only 39% of the 181 children with persistent symptoms were
      receiving daily antiinflammatory agents as recommended in the guidelines of the
      NHLBI. In response to the scenario of an acute exacerbation of asthma, no one
      mentioned that they would refer to a written plan, only 1 caretaker would measure
      peak flow and 36% would give beta-agonists. Two percent would give oral steroids
      initially, and 1 additional person would do so if wheezing continued 40 minutes
      later. Only 4% responded that they would contact their clinician. Reports of
      actual practice differed from the scenario responses in that more people began
      beta-agonists and oral steroids in response to an exacerbation in the past 6
      months than said they would in response to the scenario. CONCLUSION: In this
      population of previously hospitalized inner-city children with asthma, the NHLBI
      guidelines for the home management of asthma exacerbations are not being
      followed. Interventions are needed to affect both clinician and caretaker
      practices.

PMID- 9925836
TI  - Hair and skin disorders as signs of mitochondrial disease.
AB  - OBJECTIVE: To compare and explore the skin manifestations of mitochondrial
      disorders in 14 children with puzzling and unexpected cutaneous presentations.
      STUDY DESIGN: One hundred forty children with mitochondrial disorders who had
      been under observation in our hospital for the last 10 years, were carefully
      examined by the same physicians. Skin and hair characteristics were investigated
      by the same dermatologist. All the children developed an early unexplained
      association of symptoms. Metabolic screening for abnormal oxidative-reduction in
      plasma and mitochondrial enzyme investigations confirmed the diagnosis of
      oxidative phosphorylation disorders. RESULTS: Fourteen children with
      mitochondrial disorders (10% of the original cohort) developed specific hair and
      skin abnormalities. Their cutaneous manifestations were similar, and could be
      classified into four categories: hair abnormalities, rashes and pigmentation
      disorders, hypertrichosis, and acrocyanosis. In 3 cases, skin disorders
      constituted the puzzling and unexpected manifestations of mitochondrial disease.
      Respiratory chain deficiencies in the cultured skin fibroblasts of 3 patients and
      heteroplasmic mitochondrial DNA rearrangement in the skin fibroblasts of 1
      patient indicated that mitochondrial disorders may be expressed in the skin.
      CONCLUSION: Hair abnormalities and pigmented skin eruptions might belong to the
      broad spectrum of presenting symptoms of mitochondrial disease. The association
      of these dermatologic lesions with unrelated disorders should lead physicians to
      consider a diagnosis of mitochondriopathy as early as possible.

PMID- 9925837
TI  - Feeding strategies for premature infants: randomized trial of gastrointestinal
      priming and tube-feeding method.
AB  - BACKGROUND: Data on enteral feeding management of premature infants are limited
      and often not the subject of randomized clinical trials. Several small studies
      suggest benefits from the early initiation of feeding, but do not assess the
      combined effects of time of initiation of feeding, tube-feeding method, and type
      of milk used. Either singly or in combination, these treatments may affect
      growth, bone mineralization, biochemical measures of nutritional status, and
      feeding tolerance, and, ultimately, the duration of hospitalization. METHODS: A
      total of 171 premature infants, stratified by gestational age (26 to 30 weeks)
      and diet (human milk or preterm formula) were assigned randomly among four
      treatment combinations in a balanced two-way design comparing the presence or
      absence of gastrointestinal (GI) priming for 10 days and continuous infusion
      versus intermittent bolus tube-feeding. RESULTS: The major outcome, time required
      for infants to attain full oral feeding, was similar among treatments. GI priming
      was not associated with any measured adverse effect and was associated with
      better calcium and phosphorus retention, higher serum calcium and alkaline
      phosphatase activity, and shorter intestinal transit times. The bolus tube
      feeding method was associated with significantly less feeding intolerance and
      greater rate of weight gain than the continuous method. In addition, the greater
      the quantity of human milk fed, the lower the morbidity. CONCLUSIONS: Early GI
      priming with human milk, using the bolus tube-feeding method, may provide the
      best advantage for the premature infant.

PMID- 9925838
TI  - Clinical use of continuous arterial blood gas monitoring in the pediatric
      intensive care unit.
AB  - CONTEXT: Continuous arterial blood gas monitoring is a new technology based on
      the combination of opto-chemical and fiber-optic detectors that can measure pH,
      PCO2, PO2, and temperature on a continuous basis via a sensor placed in an
      artery. OBJECTIVE: To evaluate this technology in pediatric patients who would
      normally require frequent arterial blood gas sampling. DESIGN: A criterion
      standard study in which the results of arterial blood gas samples measured by the
      laboratory analyzer were compared with the sensor readings. SETTING: A pediatric
      intensive care unit of a tertiary referral center. PATIENTS: Children with severe
      respiratory failure who required frequent arterial blood gas sampling and who had
      a 20-gauge arterial line in either a radial or femoral site. RESULTS: Twenty-four
      patients with a mean age of 6.4 years (range 1-21 years) had a sensor placed.
      Sensors were in place for a mean of 101 +/- 62 hours. Eighteen patients underwent
      continuous monitoring for at least 24 hours or until no longer clinically
      necessary. There were 414 pairs of blood gas samples obtained. The bias/precision
      for pH was 0.005/0.030; for PCO2, -1.8/6.3 mm Hg; and for PO2, 1.2/24 mm Hg. The
      correlation (r value) between the sensor readings and the blood gases were pH 0.
      960, PCO2 0.927, PO2 0.813 (P <.01 for all values). The bias and precision for
      PO2 levels < 70 mm Hg were 0.057/9.34 mm Hg. There were no complications from
      sensor placement. Continuous blood gas monitoring allowed immediate recognition
      of clinical changes. CONCLUSION: The continuous arterial blood gas sensor is
      capable of clinically accurate blood gas measurements. This technology provides
      the clinician with immediate data that can allow rapid interventions in unstable
      patients.

PMID- 9925839
TI  - Causes of death in the extremely low birth weight infant.
AB  - OBJECTIVE: To present primary and secondary causes of death confirmed by autopsy
      for the extremely low birth weight infant. METHODS: A total of 111 infants
      weighing between 300 and 1000 g at birth who died and were autopsied at our
      hospital during the 4-year period 1990-1993 were retrospectively reviewed.
      Clinical, pathologic, and laboratory data were retrieved including results of
      placental examinations and autopsy cultures. Primary and secondary causes of
      death were assigned by the authors. RESULTS: Infection was the most common
      primary cause (56/111) followed by respiratory distress syndrome/bronchopulmonary
      dysplasia (24/111) and congenital defect (15/111). Immaturity as an only cause
      appeared almost exclusively in infants weighing <500 g at birth. Infection was
      significantly underdiagnosed clinically with most of these deaths attributed to
      immaturity or respiratory distress syndrome. In only 1 case was intraventricular
      hemorrhage considered the primary cause of death although it was present as a
      secondary cause in 19/111. Infections were divided into congenital (30/56) and
      acquired (26/56) by time of death. The congenital infections (</=48 hours)
      consisted of pneumonia and chorioamnionitis/funisitis attributable to maternal
      enteric organisms. Causative bacteria were obtained in pure culture in a number
      of these cases. The acquired infections were mainly caused by yeasts and
      nosocomial bacteria. Sixty-seven percent of the deaths occurred in the first 2
      days and 12% were beyond the neonatal period at 29 to 104 days. Care was not
      initiated or was withdrawn in 50% of the infants, usually within the first 4
      hours. CONCLUSIONS: Infection of the amniotic fluid leading to pneumonia was the
      major cause of death in the extremely low birth weight infant. Accurate cause of
      death can not be reliably ascertained without an autopsy accompanied by
      examination of the placenta in the early deaths. Antibiotic treatment of the
      mother and infant may have reduced the deaths from infection. Early failure to
      respond to neonatal intensive care may well indicate presence of a congenital
      pneumonia.

PMID- 9925840
TI  - Regulation of arginine vasopressin in enuretic children under fluid restriction.
AB  - BACKGROUND: Treatment of primary nocturnal enuresis using 1-deamino-8-D-arginine
      vasopressin is based on the hypothesis that antidiuretic hormone (arginine
      vasopressin [AVP]) secretion is insufficient during the night. Persisting doubts
      about the theoretical background of this treatment and first results pointing to
      a different AVP regulation in children with nocturnal enuresis were the motives
      for the present study. OBJECTIVE: To determine if children with primary nocturnal
      enuresis have different AVP levels during fluid restriction when compared with
      normal controls. METHODS: Twenty-three children with nocturnal enuresis (median
      age, 11 years) were compared with a corresponding control group of 18 healthy
      children. Plasma osmolality, urine osmolality, and plasma AVP concentrations were
      determined before and after a defined fluid restriction. RESULTS: Regarding
      plasma and urine osmolality, no differences were found between the two groups.
      AVP levels after fluid restriction, however, showed significant differences. To
      maintain osmolality, the plasma AVP concentrations of the controls rose to a
      median value of 5.7 pg/mL (range: 0.9-29.0 pg/mL) in comparison to a median of
      14.0 pg/mL (range: 3.5-64.0 pg/mL, P =. 015) for the enuretic children.
      CONCLUSION: The results are consistent with the established fact that AVP
      secretion is a function of plasma osmolality. They contradict the hypothesis that
      enuretic children have a AVP deficiency that has to be supplemented. Rather, the
      results point to a defect at the AVP receptor level or of the signal transduction
      pathway.

PMID- 9925841
TI  - Mitochondrial dysfunction in skeletal muscle of children with cardiomyopathy.
AB  - OBJECTIVES: This study sought to examine skeletal muscle of children with
      cardiomyopathy (CM) for changes in mitochondrial enzyme activities and in
      mitochondrial DNA (mtDNA). BACKGROUND: Heart mitochondrial enzymatic activity
      defects have been often found in dilated and hypertrophic CM. The defects
      primarily involve the activities of the electron transport system and oxidative
      phosphorylation pathway including respiratory complexes I, III, IV, and V.
      METHODS: Skeletal muscle biopsies of 8 children with CM were examined for
      specific mitochondrial enzyme activities, mtDNA copy number and the presence of
      pathogenic mutations and deletions in mtDNA. RESULTS: A marked deficiency in
      specific mitochondrial enzyme activities was found in 6 of 8 patients in skeletal
      muscle as well as in 2 of 3 hearts of those in whom cardiac tissue was available.
      Specific activity defects were found in complex I (2 cases), complex III (5
      cases), complex IV (3 cases), and complex V (4 cases). Complex II and citrate
      synthase activities were unaffected. None of the previously reported pathogenic
      mutations associated with CM were detected, nor was there any evidence of mtDNA
      depletion. The incidence of defective respiratory complex activities in skeletal
      muscle was similar to the incidence of defective complex activities previously
      reported in cardiac tissue. CONCLUSIONS: Mitochondrial analysis of skeletal
      muscle is warranted in the overall clinical evaluation of children with CM, and
      particularly before consideration for cardiac transplantation.

PMID- 9925842
TI  - Vertebral artery compression resulting from head movement: a possible cause of
      the sudden infant death syndrome.
AB  - OBJECTIVE: Vertebral artery compression causing brainstem ischemia has been
      suggested to underlie the sudden infant death syndrome. Vertebral artery
      distortion from neck movements has been demonstrated by angiography in infants,
      but direct evidence for arterial compression is lacking. In an attempt to
      demonstrate vertebral artery compression from head movement, we examined at
      postmortem the vertebral arteries of infants after neck extension or rotation.
      METHODS: The C1-C7 spinal column, together with a 2-cm rim of skull base, was
      removed from 20 infants dying from sudden infant death syndrome or other causes.
      In 5 cases the neck was extended, in 9 cases it was rotated 90 degrees to the
      right, and in 6 cases the neck was held in the neutral position. The neck was
      maintained in these positions during formalin fixation, and serial sections of
      selected blocks were examined microscopically. RESULTS: In 3 of 5 extended cases,
      bilateral vertebral artery compression was seen between the occipital bone and
      C1. In 3 of 9 rotated cases, the left vertebral artery was compressed adjacent to
      C1 before the artery entered the transverse foramen. No vertebral artery
      compression was seen in the necks held in the neutral position. CONCLUSIONS: The
      vertebral arteries of some infants can be compressed by neck movement. This could
      induce lethal brainstem ischemia in infants with inadequate collateral blood flow
      or with poor compensatory arterial dilatation, and may underlie some cases of
      sudden infant death syndrome.

PMID- 9925843
TI  - Cisapride: a survey of the frequency of use and adverse events in premature
      newborns.
AB  - OBJECTIVE: This survey estimated the frequency of use and adverse events
      associated with cisapride treatment of premature newborns in intensive care
      units. It was initiated in response to a warning issued in Canada cautioning
      against cisapride treatment of premature infants of <36 weeks' gestation and <3
      months of age. METHODOLOGY: Surveys were mailed to 105 neonatology training
      program directors to obtain the total number of neonatal intensive care unit
      (NICU) admissions, the number of admissions of infants of <36 weeks' gestation,
      the number of years that cisapride had been used, the estimated percent/number of
      premature patients treated with cisapride per year, and the frequency and nature
      of arrhythmias or other adverse events associated with cisapride treatment. Of
      105 programs, 46 responded to a single mailing of the first survey. A second
      survey mailed to the 45 respondents to the first survey sought to determine the
      indications, diagnostic tests, and dosages used with cisapride treatment of
      premature newborns. Of the 45 programs, 26 responded to the second survey.
      RESULTS: More than 58 000 premature newborns of <36 weeks' gestation were
      admitted to the NICUs we surveyed, and approximately 19% were treated with
      cisapride. No deaths attributable to cisapride were reported among >11 000
      preterm newborns treated. Three nonfatal arrhythmias were reported; two
      associated with 10-fold dosing errors and one with co-treatment with
      erythromycin, a macrolide antibiotic that reduces the metabolism of cisapride.
      Diarrhea was reported in 12 patients, and reversible liver enzyme changes were
      noted in one patient. Typically, cisapride treatment was started in dosages of
      0.1 to 0.2 mg/kg/dose, repeated every 6 to 8 hours. Treatment usually was begun
      empirically, without a preceding study to document gastroesophageal reflux. The
      most frequent indications for cisapride treatment were choking or gagging, with
      associated apnea, bradycardia, and desaturation. Approximately 50% of patients
      had discontinued cisapride treatment before discharge. Eighty-four percent of
      clinicians judged cisapride to be effective for the problems being treated.
      CONCLUSIONS: Cisapride treatment of premature infants of <36 weeks' gestation and
      <3 months of age in NICUs appears to be widespread in the United States.
      Complications and adverse events were seen when cisapride was administered in
      excessive dosages or in combination with a drug that inhibits its metabolism and
      leads to increased serum concentrations. Severe toxicities such as arrhythmias
      were reported with a frequency of <1/11 000 NICU admissions. However, in a
      retrospective survey, episodes of toxicity, including mortality, attributable to
      cisapride may not have been recognized or reported.

PMID- 9925844
TI  - The hospitalist movement and its implications for the care of hospitalized
      children.

PMID- 9925845
TI  - The early history of the infant mortality rate in America: "A reflection upon the
      past and a prophecy of the future".

PMID- 9925846
TI  - Experimental validation of neonatal feeding practices.

PMID- 9925847
TI  - Predicting hyperbilirubinemia in newborns: the importance of timing.

PMID- 9925848
TI  - Comments on palivizumab (Synagis)

PMID- 9925849
TI  - A hospitalist movement? Where to?

PMID- 9925850
TI  - Erythema induratum of Bazin in an infant.

PMID- 9925852
TI  - Polyarteritis nodosa attributable to minocycline treatment for acne vulgaris.

PMID- 9925851
TI  - Metastatic Crohn's disease presenting as chronic perivulvar and perirectal
      ulcerations in an adolescent patient.

PMID- 9925853
TI  - Moyamoya syndrome in children with Alagille syndrome: additional evidence of a
      vasculopathy.

PMID- 9925854
TI  - Planning for children whose parents are dying of HIV/AIDS. American Academy of
      Pediatrics. Committee on Pediatric AIDS, 1998-1999.
AB  - Although the character of acquired immunodeficiency syndrome is changing into a
      chronic illness, it is estimated that by the end of this century, 80 000 children
      and adolescents in the United States will be orphaned by parental death caused by
      human immunodeficiency virus infection. Plans for these children need to be made
      to ensure not only a stable, consistent environment that provides love and
      nurturing, but also the medical and social interventions necessary to cope with
      the tragic loss. Pediatricians should become aware of local laws and community
      resources and initiate discussion early in the course of parental illness to
      facilitate planning for the future care and custody of the children. States need
      to adopt laws and regulations that provide flexible approaches to guardianship
      and placement of children orphaned by acquired immunodeficiency syndrome.

PMID- 9925855
TI  - Guidelines for the pediatric perioperative anesthesia environment. American
      Academy of Pediatrics. Section on Anesthesiology.
AB  - The American Academy of Pediatrics proposes the following guidelines for the
      pediatric perioperative anesthesia environment. Essential components are
      identified that make the perioperative environment satisfactory for the
      anesthesia care of infants and children. Such an environment promotes the safety
      and wellbeing of infants and children by reducing the risk for adverse events.

PMID- 9925856
TI  - Adolescent pregnancy--current trends and issues: 1998 American Academy of
      Pediatrics Committee on Adolescence, 1998-1999.
AB  - Although the prevention of unintended adolescent pregnancy is a primary goal of
      the American Academy of Pediatrics and society, many adolescents continue to
      become pregnant. Since the last statement on adolescent pregnancy was issued by
      the Academy in 1989, new observations have been recorded in the literature. The
      purpose of this new statement is to review current trends and issues on
      adolescent pregnancy to update practitioners on this topic.

PMID- 9925857
TI  - How pediatricians can respond to the psychosocial implications of disasters.
      American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and
      Family Health, 1998-1999.
AB  - Natural and human-caused disasters, violence with weapons, and terrorist acts
      have touched directly the lives of thousands of families with children in the
      United States.1 Media coverage of disasters has brought images of floods,
      hurricanes, and airplane crashes into the living rooms of most American families,
      with limited censorship for vulnerable young children. Therefore, children may be
      exposed to disastrous events in ways that previous generations never or rarely
      experienced. Pediatricians should serve as important resources to the community
      in preparing for disasters, as well as acting in its behalf during and after such
      events.

PMID- 9925858
TI  - The hospital record of the injured child and the need for external cause-of
      injury codes. American Academy of Pediatrics. Committee on Injury and Poison
      Prevention, 1998-1999.
AB  - Proper record-keeping of emergency department visits and hospitalizations of
      injured children is vital for appropriate patient management. Determination and
      documentation of the circumstances surrounding the injury event are essential.
      This information not only is the basis for preventive counseling, but also
      provides clues about how similar injuries in other youth can be avoided. The
      hospital records have an important secondary purpose; namely, if sufficient
      information about the cause and mechanism of injury is documented, it can be
      subsequently coded, electronically compiled, and retrieved later to provide an
      epidemiologic profile of the injury, the first step in prevention at the
      population level. To be of greatest use, hospital records should indicate the
      "who, what, when, where, why, and how" of the injury occurrence and whether
      protective equipment (eg, a seat belt) was used. The pediatrician has two
      important roles in this area: to document fully the injury event and to advocate
      the use of standardized external cause-of-injury codes, which allow such data to
      be compiled and analyzed.

PMID- 9925859
TI  - Newborn and infant hearing loss: detection and intervention.American Academy of
      Pediatrics. Task Force on Newborn and Infant Hearing, 1998- 1999.
AB  - This statement endorses the implementation of universal newborn hearing
      screening. In addition, the statement reviews the primary objectives, important
      components, and recommended screening parameters that characterize an effective
      universal newborn hearing screening program.

PMID- 9925860
TI  - Hepatitis B vaccination of premature infants: a reassessment of current
      recommendations for delayed immunization.
AB  - OBJECTIVE: Current American Academy of Pediatrics and United States Public Health
      Service Immunization Practices Advisory Committee recommendations for hepatitis B
      immunization in premature infants weighing <2 kg at birth born to hepatitis B
      surface antigen (HBSAg)-negative mothers are to delay the initiation of
      vaccination until such infants reach 2 kg or until 2 months of age. This proposal
      to delay vaccination at birth in these low-risk infants was based on limited
      studies not conducted in the United States. We sought to reassess current
      recommendations to delay administration of hepatitis B vaccine in low-risk
      premature infants by determining the immunogenicity of early hepatitis B
      vaccination in a US population and identifying variables associated with poor
      immunogenicity. METHODS: A total of 148 infants <37 weeks' gestation born to
      mothers negative for HBSAg were recruited at birth and stratified to three birth
      weight groups: <1000 g, 1000 to 1500 g, and >1500 g. Recombinant hepatitis B
      vaccine was administered within the first week of life, at 1 to 2 months of age,
      and at 6 to 7 months of age. Serum obtained at birth and after the second and
      third doses of vaccine was tested for antibody to HBSAg. Variables associated
      with poor response were sought prospectively by collecting demographic and
      clinical data. RESULTS: A total of 118 subjects (83%) completed the study.
      Postsecond dose sera were available for 117 infants and postthird dose sera were
      available for 112 infants. The seroprotection rate (attaining >/=10 mIU/mL HBS
      antibody) after two doses was low (25%) regardless of birth weight; infants
      weighing <1000 g at birth had the poorest response (11%). The seroprotection
      response rate after three doses of vaccine increased with birth weight; infants
      weighing </=1500 g at birth (groups 1 and 2) had lower rates of response (52% and
      68%, respectively) than did infants weighing >1500 g at birth (group 3; 84%
      response rate). The seroprotection response rate of group 3 infants after three
      doses of vaccine, although low, could not be differentiated from the response
      rates reported for full-term infants using 95% confidence intervals. Of all
      infants who did not achieve protective levels of antibody after three doses of
      vaccine, 96% (26/27) weighed <1700 g at birth. The geometric mean HBS antibody
      levels in responders were 88 and 386 mIU/mL after two and three doses,
      respectively. Of 36 children with a birth weight >1500 g, 33 (91%) achieved
      levels of HBS antibody >100 mIU/mL after three doses of vaccine, compared with
      25/35 (71%) of infants with birth weight <1500 g. Using logistic regression
      analysis, nonresponders were more likely than were responders to have been
      treated with steroids (26% vs 9%) and to have had a low birth weight (1037 g vs
      1455 g). In addition, the seroresponse rate of black infants was more likely than
      that of white infants to be associated with poor weight gain (falling off 2
      percentile ranks in weight) in the first 6 months of life: 22% of black and 60%
      of white children who failed to gain weight adequately responded to vaccination,
      compared with 92% of black and 70% of white children who were growing adequately.
      Of interest, the only infant with a birth weight of >1700 g who did not make
      protective levels of specific antibody after three doses of vaccine was 2300 g at
      birth, but had inadequate weight gain in the first 6 months of life. CONCLUSIONS:
      This study supports current recommendations of the American Academy of Pediatrics
      and the Centers for Disease Control and Prevention for delaying the initiation of
      hepatitis B immunization beyond the first week of life for premature infants at
      low risk for hepatitis B infection, particularly in newborns weighing <1700 g at
      birth. In addition, we have identified variables other than birth weight that
      were associated with an inadequate immune response to early hepatitis B
      vaccination in premature infants, such as poor weight gain in the first 6 months
      of life

PMID- 9925861
TI  - Chest roentgenogram in the evaluation of heart defects in asymptomatic infants
      and children with a cardiac murmur: reproducibility and accuracy.
AB  - OBJECTIVES: To evaluate the reproducibility and the accuracy of pediatric
      radiologists' assessments of chest radiographs with respect to the presence or
      absence of heart defects in children with an asymptomatic heart murmur. DESIGN:
      Ninety-eight children, ages 1 month to 15 years (median, 30.1 months), referred
      for evaluation of a heart murmur were consecutively included. They all had a
      standard chest radiograph and a color Doppler echocardiograph (CDE) performed.
      Six specialists in pediatric radiology evaluated the chest radiographs
      independently on two occasions 6 months apart. The radiologists were asked to
      classify each set of films into one of two categories: heart disease or no heart
      disease. The outcome of the CDE was considered the definite diagnosis. kappa
      statistics were used to analyze the reproducibility of the radiologic
      assessments. Sensitivity, specificity, and the predictive value of a positive and
      a negative test were used for evaluation of the accuracy of the radiologic
      assessments. RESULTS: Mean intra- and interobserver kappa values were all <0.6,
      and the majority were <0.4. Mean sensitivity was 0.3 (range: 0.17-0.52), mean
      predictive value of a positive test was 0.4, implying that 60% of the positive
      assessments were falsely positive. Mean specificity was 0.86 (range: 0.75-0.93)
      and the mean predictive value of a negative test was 0.80 implying that 20% of
      the negative assessments were falsely negative. CONCLUSION: We found a low
      reproducibility, as well as a low accuracy, of the radiologic assessments of the
      chest radiographs of children with an asymptomatic heart murmur with respect to
      the presence or absence of heart disease. A false-positive radiologic assessment
      of the chest radiograph with respect to heart defects causes unnecessary anxiety
      and further examinations, whereas a false-negative assessment might result in
      omission of relevant investigations and proper identification of the heart
      defect. We cannot recommend the use of chest radiographs in the initial
      evaluation of the asymptomatic child with a heart murmur. If a heart defect
      cannot be excluded by clinical examination a CDE must be performed.

PMID- 9925862
TI  - Recombinant human erythropoietin treatment for chemotherapy-related anemia in
      children.
AB  - OBJECTIVE: The efficacy and safety of recombinant human erythropoietin (rHuEPO)
      treatment in chemotherapy-induced anemia in children were investigated. rHuEPO is
      used to treat chemotherapy-induced anemia. Several studies recommend 150 to 300
      IU/kg rHuEPO for 2 to 8 months. There are only a few controlled trials in
      children and no precise data about the optimal dose and duration of rHuEPO
      treatment is available. PATIENTS AND METHODS: Thirty-four patients receiving
      chemotherapy for treatment of their solid tumors between October 1996 and June
      1997 were included in this study. Patients were randomly selected for each group.
      The male/female ratio was 20/14, and the median age was 5 years (range, 1-16
      years). They had normal hemoglobin levels at the time of diagnosis. When
      hemoglobin levels decreased to levels lower than 10 g/dL, rHuEPO (150 IU/kg/d, 3
      times a week, subcutaneously) was given to 17 patients for 2 months. Their renal,
      liver, and pulmonary functions were normal. None of the patients had hematologic
      disease. We did not use any other drugs such as iron or granulocyte colony
      stimulating factor. There were 17 patients in the control group. Fifteen patients
      got chemotherapy regimens including cisplatin (CDDP), but 19 were treated with
      regimens without CDDP. At the end of rHuEPO treatment, all patients were examined
      in terms of transfusion requirements and rate of change in hemoglobin levels.
      RESULTS: One patient in the study group needed a blood transfusion, whereas 8
      patients needed a transfusion in the control group. Patients in the study group
      had less transfusion requirements compared with the control group. The mean
      hemoglobin levels before and after the study were 8.48 +/- 0.98 g/dL and 8.41 +/-
      1.65 g/dL in the control group and 8.50 +/- 0.85 g/dL and 10.21 +/- 2.14 g/dL in
      the rHuEPO group, respectively. Optimal hemoglobin increments began in 4 weeks
      and continued during treatment. CDDP-receiving and CDDP-nonreceiving groups did
      not have any difference in pretreatment serum erythropoietin levels. rHuEPO
      treatment was more effective in patients treated with non-CDDP regimens. Mean
      hemoglobin level increased from 8.68 +/- 0.73 g/dL to 10.26 +/- 1.84 g/dL in 9
      patients treated with non-CDDP chemotherapy regimens in the erythropoietin group,
      although it increased from 8.28 +/- 0.97 g/dL to 10.15 +/- 2.5 g/dL in 8 patients
      treated with CDDP-containing regimens in the erythropoietin group. rHuEPO caused
      high blood pressure in only 1 patient that resolved spontaneously after cessation
      of erythropoietin treatment for a week. CONCLUSION: rHuEPO treatment (150 IU/kg/d
      3 times a week) is effective and safe in children with chemotherapy-induced
      anemia. It decreases blood transfusion requirements in solid tumor patients. Our
      results show that the response to rHuEPO in CDDP-induced anemia is less than the
      response in non-CDDP receiving patients. Higher doses may be necessary in
      patients using CDDP.

PMID- 9925863
TI  - Assessment of infant cardiopulmonary resuscitation rescue breathing technique:
      relationship of infant and caregiver facial measurements.
AB  - OBJECTIVE: Although a few infants ever require resuscitation, pediatric
      cardiopulmonary resuscitation (CPR) is performed most commonly under 1 year of
      age. American Heart Association guidelines for pediatric basic life support
      recommend that the caregiver place his/her mouth over the infant's mouth and nose
      to create a seal. The way CPR is currently taught encourages parents to attempt
      to seal the nose and open the mouth of the infant for rescue breathing. Recent
      studies suggest some parents may have trouble sealing an infant's nose and open
      mouth, but their study participant numbers were small. The aim of this report is
      to estimate, among a large cohort, the ability of caregivers to create a seal to
      their infants for the provision of rescue breathing according to current
      guidelines. METHODS: Infants up to 1 year of age (n = 281) and their caregivers
      were enrolled from Philadelphia pediatric offices. Facial measurements of the
      infants were obtained to estimate the length needed to seal the nose and open
      mouth, and the nose and closed mouth. Mouth widths of the caregivers were
      compared with their infant's nose and mouth lengths. One-way analysis of variance
      with Tukey's postmortem analysis and ordinary least squares means regression were
      used for univariate analysis with analysis of covariance used to control for the
      effects of multiple variables when necessary. Infant measurements were stratified
      into 3-month age quadrants to compare against matched adult caregiver
      measurements. RESULTS: Most caregivers (n = 270) were female. Females had smaller
      mouth widths than males (4.9 +/- 0.5 cm vs 5.2 +/- 0.5 cm). Infant nose and mouth
      length increased during the first year of life, with the largest increase between
      0 to 3 months and 3 to 6 months (4.2 +/- 0.4 cm to 4.7 +/- 0.4 cm). As infant age
      and face length increased, a progressively higher rate of adult females were
      estimated not to be able to cover their infant's nose and open mouth, with the
      greatest increase again between 0 to 3 months (9%) and 3 to 6 months (40%). All
      female caregivers except 1 were predicted to be able to seal their infant's nose
      and closed mouth by our measurements. CONCLUSIONS: Infant face length grows
      rapidly during the first year of life with the most rapid growth occurring during
      the first 6 months. As early as 3 to 6 months of infant age, many adult
      caregivers' facial measurements, especially female, predict that they may not be
      able to form a seal for mouth-to-nose and open-mouth infant rescue breathing. By
      related measurements, nearly 100% of caregivers should be able to seal their
      infant's nose and closed mouth. If facial measurement predictions correlate with
      functional inability to seal an infant's nose and open mouth, infant CPR rescue
      breathing instruction will need to emphasize head position and creation of a seal
      over the mouth and nose without teaching that the mouth be open. pediatric basic
      life support, infant CPR, rescue breathing, sudden infant death syndrome, acute
      life-threatening episode.

PMID- 9925864
TI  - Central nervous system manifestations of childhood shigellosis: prevalence, risk
      factors, and outcome.
AB  - BACKGROUND AND OBJECTIVE: Alterations in consciousness, including seizures,
      delirium, and coma, are known to occur during Shigella infection. Previous
      reports have suggested that febrile convulsions and altered consciousness are
      more common during shigellosis than with other childhood infections. Those
      reports, however, have been from locations where S dysenteriae type 1 was not
      common, thus making it difficult to assess the specific contribution that S
      dysenteriae type 1 infection, and Shiga toxin, might make to the pathogenesis of
      altered consciousness in children with shigellosis. In this study we seek to
      determine the prevalence, risk factors, and outcome of altered consciousness in
      children with shigellosis in Bangladesh, a country where infection with all four
      species of Shigella is common. We particularly focus on the importance of
      metabolic abnormalities, which we have previously shown to be a common feature of
      shigellosis in this population. METHODS: This study was conducted at the Diarrhea
      Treatment Centre of the International Centre for Diarrhoeal Disease Research,
      Bangladesh in Dhaka, Bangladesh, which provides care free of charge to persons
      with diarrhea. During 1 year, a study physician identified all inpatients
      infected with Shigella by checking the logs of the Clinical Microbiology
      Laboratory daily. Study physicians obtained demographic and historical
      information by reviewing the patient charts and by interviewing patients, or
      their parents or guardians, to confirm or complete the history of illness
      obtained on admission. Patients were categorized as being conscious or
      unconscious based on a clinical scale; having a seizure documented in the
      hospital; or having a seizure by history during the current illness that was not
      witnessed by medical personnel. Patient outcome was classified as discharged
      improved, discharged against medical advice, transferred to another health
      facility, or died in the Treatment Centre. Laboratory examinations were ordered
      at the discretion of the attending physician; all such information was recorded
      on the study form. Clinical management was by the attending physician. Factors
      independently predictive of a documented seizure, or of unconsciousness, were
      determined using a multiple logistic regression analysis. For this analysis
      variables associated with unconsciousness or a documented seizure in the analysis
      of variance or chi2 analyses were entered into the regression equation and
      eliminated in a backward stepwise fashion if the probability associated with the
      likelihood ratio statistic exceeded .10. RESULTS: During this 1-year study, 83
      402 persons with diarrhea came to the Treatment Centre for care, and 6290
      patients were admitted to the inpatient unit. Shigella was isolated from a stool
      or rectal swab sample of 863 (13.7%) of the inpatients. Seventy-one (8%) of the
      inpatients with shigellosis were >/=15 years old; 61 (86%) were conscious; 10
      (14%) were unconscious; none had either a documented seizure or a seizure by
      history during this illness. Seven hundred ninety-two patients were <15 years old
      (92%); 654 (83%) were conscious; 73 (9%) were unconscious; 41 (5%) had a
      documented seizure (compared with >/=15-year age group); 24 (3%) had a seizure by
      history during this illness. Of the 41 patients with documented seizures, 19
      (46.3%) had a seizure at the time of admission, and 22 (53.7%) had a seizure
      after admission. Twenty-five (61.0%) of the 41 patients with documented seizures
      were reported to have a seizure during this illness before coming to the
      Treatment Centre. Clinical features that are known to cause altered consciousness
      fever, severe dehydration, hypoglycemia, hyponatremia, or meningitis-were present
      in 38 (92.7%) of the 41 patients in whom a seizure was witnessed and in 67
      (91.8%) of the 73 patients who were unconscious. Nineteen (46. 3%) of the
      patients who had a seizure documented had two of these five features, 4 (9.8%)
      had three, and 1 (2. (ABSTRACT TRUNCATED)

PMID- 9925865
TI  - Lipoid pneumonia: a silent complication of mineral oil aspiration.
AB  - INTRODUCTION: Chronic constipation is a common symptom in pediatrics, and
      physicians often use mineral oil to treat chronic constipation in children.
      Mineral oil, a hydrocarbon, may not elicit a normal protective cough reflex and
      may impair mucociliary transport. These effects can increase the likelihood of
      its aspiration and subsequent impaired clearance from the respiratory tract. We
      report a case of a child with neurodevelopmental delay with chronic constipation
      and a history of chronic mineral oil ingestion presenting as asymptomatic
      exogenous lipoid pneumonia (ELP). CASE HISTORY: A 6-year-old white boy with a
      history of developmental delay was found to have an infiltrate in his right upper
      lobe on a chest radiograph obtained during evaluation for thoracic scoliosis. The
      patient had a long history of constipation with daily use of mineral oil. He was
      fed by mouth and had occasional episodes of coughing and choking during feeding.
      He was asymptomatic at presentation and physical examination was unremarkable.
      The patient was advised to stop administration of the mineral oil and was treated
      empirically with antibiotics during a 3-month period. At follow-up examination
      the patient continued to be asymptomatic, with the radiologic persistence of the
      infiltrate. Diagnosis of lipoid pneumonia was made by diagnostic bronchoscopy
      with bronchoalveolar lavage (BAL). The exogenous origin of the lipid in the BAL
      fluid was confirmed by gas chromatography/mass spectrometry. DISCUSSION: The
      clinical presentation of ELP is nonspecific and ranges from the totally
      asymptomatic patient with incidental radiologic finding, like our patient, to the
      patient with acute or chronic symptoms attributable to pneumonia, pulmonary
      fibrosis, or cor pulmonale. Bronchoscopy with BAL can be successful in
      establishing the diagnosis of ELP by demonstration of a high lipid-laden
      macrophage index. Treatment of ELP in children is generally supportive, with the
      symptoms and roentgenographic abnormalities resolving within months after
      stopping the use of mineral oil. CONCLUSION: Lipoid pneumonia as a result of
      mineral oil aspiration still occurs in the pediatric population. It can mimic
      other diseases because of its nonspecific clinical presentation and radiographic
      signs. In patients with swallowing dysfunction and pneumonia, a history of
      mineral oil use should be obtained and a diagnosis of ELP should be considered in
      the differential diagnoses if mineral oil use has occurred. Our case points to
      the need for increased awareness by the general pediatricians of the potential
      hazards of mineral oil use for chronic constipation.

PMID- 9925866
TI  - Clinical and hematologic features do not reliably identify children with
      unsuspected meningococcal disease.
AB  - OBJECTIVE: To determine the frequency of unsuspected meningococcal disease (UMD)
      in young febrile children with meningococcal infections and evaluate whether
      clinical and laboratory parameters commonly used in the evaluation of fever can
      help identify children with UMD. METHODS: We reviewed the records of children
      with meningococcal disease from 1985 to 1996 at four referral centers. Children
      who were evaluated as outpatients and then discharged to home, from whom
      Neisseria meningitidis was isolated from blood or cerebrospinal fluid cultures
      obtained during these outpatient visits, were considered to have UMD. We compared
      clinical and laboratory parameters between these children and 6414 febrile
      outpatients 3 to 36 months old with negative blood cultures enrolled in a
      separate study of occult bacteremia. RESULTS: We identified 381 children with
      meningococcal disease, of whom 45 (12%) had UMD. Of the 45 with UMD, 37 (82%)
      were 3 to 36 months old. Compared with the 6414 culture-negative patients, these
      37 patients with UMD were significantly younger (8.9 +/- 5.4 vs 14.2 +/- 8.1
      months) and had significantly higher band counts (14.3 +/- 11.1 vs 7.3 +/- 7.5%).
      There were no significant differences, however, in temperature, white blood cell
      counts, and absolute neutrophil counts. Multivariate analysis identified young
      age and the band count as independent predictors of UMD. CONCLUSIONS: Children
      ultimately diagnosed with meningococcal disease have commonly been evaluated as
      outpatients and discharged to home before diagnosis. Of the hematologic
      parameters frequently used in the evaluation of fever, only the band count
      differs significantly between young febrile children with UMD and those with
      negative cultures. Because UMD is uncommon in young febrile pediatric
      outpatients, however, the predictive value of the band count is low. Thus, the
      complete blood count is not routinely helpful for the diagnosis of UMD.

PMID- 9925867
TI  - Human immunodeficiency virus status and delayed-type hypersensitivity skin
      testing in Ugandan children.
AB  - BACKGROUND: In previous studies, delayed-type hypersensitivity (DTH) skin testing
      has been shown to be affected by several factors including nutritional status,
      intercurrent infection, host immune status, and previous exposure to the antigen
      being used. OBJECTIVE: To determine the effect of human immunodeficiency virus
      type 1 (HIV-1) status on DTH skin testing in a cohort of HIV-1-infected and
      noninfected Ugandan children followed prospectively from birth. DESIGN: Nested
      case-control study. SETTING: Primary care clinic serving study participants at
      Mulago Hospital, Makerere University, Kampala, Uganda. PARTICIPANTS: Thirty HIV-1
      infected children and 30 age-matched, HIV-1-noninfected children. METHODS: After
      completion of history and physical, each child underwent Mantoux skin testing
      with both Candida and purified protein derivative (PPD). Results of skin testing
      were read in 48 to 72 hours. Complete chart reviews were performed on all
      children. CD4 lymphocyte counts were obtained on all HIV-1-infected children at
      the time the skin testing was read. RESULTS: The average age of participants was
      67 months (range, 51-92 months). HIV-1-infected children (mean CD4 lymphocyte
      count, 1069 mL-1; range, 86-3378 mL-1), compared with noninfected, age-matched
      peers, developed significantly smaller PPD reaction size (mean, 1.18 mm +/- 4.3
      vs 3.6 mm +/- 7.6, respectively). Candida responses were not different between
      the two groups of children. Among HIV-1-infected children, there was a larger
      Candida reaction size in children who had recently received chloroquine
      treatment. There was no significant correlation between Candida reactivity and
      PPD reactivity, progressive HIV-1 disease, or CD4 lymphocyte count. The six
      children diagnosed clinically with active tuberculosis had lower absolute CD4
      lymphocyte counts than children without tuberculosis. Lack of reaction to PPD was
      associated with lower CD4 lymphocyte counts and progressive HIV-1 disease.
      CONCLUSIONS: In HIV-1-infected Ugandan children, DTH skin testing was influenced
      by the choice of antigen selected, HIV-1 infection, and recent treatment with
      chloroquine. Based on these findings, we believe that further prospective,
      longitudinal investigation into the role of chloroquine in HIV-1-infected
      children is needed. We emphasize the limitations of DTH skin testing in HIV
      infected children as an adjunct in the diagnosis of active tuberculosis.

PMID- 9925868
TI  - Renal medullary carcinoma in an adolescent with sickle cell trait.
AB  - We describe the complex presentation of a patient with renal medullary carcinoma,
      a newly described entity primarily affecting young patients with sickle cell
      trait. Renal medullary carcinoma is an aggressive, rapidly destructive tumor
      associated with a delayed diagnosis and a poor outcome. The most common
      presenting signs and symptoms include hematuria, abdominal or flank pain, and
      weight loss. Sickle cell trait as the sole cause of hematuria in young black
      patients is a diagnosis of exclusion. Hemoglobin electrophoresis, intravenous
      pyelography, and computed tomography scans should be the minimal studies
      performed in young black patients with hematuria.

PMID- 9925869
TI  - A comparison of the Mogen and Gomco clamps in combination with dorsal penile
      nerve block in minimizing the pain of neonatal circumcision.
AB  - OBJECTIVES: 1) To compare the Mogen and Gomco clamps with regard to pain
      experienced during neonatal circumcision, and 2) to assess neonatal circumcision
      pain with and without dorsal penile nerve block (DPNB). DESIGN/METHODS: A
      randomized, controlled, nonblinded clinical trial; 48 healthy, full-term infants
      were randomized into one of the following four groups: Gomco vs Mogen with (+) or
      without (-) DPNB. DPNB+ infants were injected with 0.8 mL of 1% lidocaine before
      circumcision. DPNB- infants received no placebo injection. Heart rate,
      respiratory rate, and oxygen saturation (SaO2) during the procedure were
      monitored and data transferred to computer files by using the Datalab software
      system. Crying was recorded on videotape. Pre- and postcircumcision saliva
      samples for cortisol analysis were collected. Heart rate, respiratory rate, SaO2,
      cortisol changes, and duration of crying were evaluated statistically with two
      way analyses of variance and t tests. RESULTS: The type of clamp but not the use
      of anesthesia was significantly associated with the length of the procedure (mean
      Mogen time, 81 seconds; mean Gomco time, 209 seconds) and percentage of
      respiratory rate change. The use of anesthesia but not the type of clamp was
      significantly associated with percentage of crying time and percentage of SaO2
      change during the procedure. Heart rate changes and total crying time were
      significantly associated with both the type of clamp and the use of anesthesia.
      Neither clamp type nor anesthesia status was significantly associated with
      salivary cortisol changes, although the mean increase for the DPNB- group was
      approximately twice that for the DPNB+ group. Fifty-six percent of infants
      circumcised with the Mogen clamp and DPNB did not cry at all during the
      procedure. CONCLUSIONS: DPNB is effective in reducing neonatal circumcision pain
      with either the Mogen or the Gomco clamp. For a given anesthesia condition, the
      Mogen clamp is associated with a less painful procedure than the Gomco. The Mogen
      clamp with DPNB causes the least discomfort during neonatal circumcision.

PMID- 9925870
TI  - Nasal continuous positive airway pressure and early surfactant therapy for
      respiratory distress syndrome in newborns of less than 30 weeks' gestation.
AB  - OBJECTIVE: To determine whether early versus late treatment with porcine
      surfactant (Curosurf) reduces the requirement of mechanical ventilation in very
      preterm infants primarily supported by nasal continuous positive airway pressure
      (nasal CPAP). DESIGN: Multicenter randomized, controlled trial. PATIENTS: The
      study population comprised 60 infants <30 weeks' gestation with respiratory
      distress syndrome (RDS) who had an arterial to alveolar oxygen tension ratio
      (a/APO2) of 0.35 to 0.22. The cohort from which the study population was
      generated comprised 397 infants. RESULTS: The need for mechanical ventilation or
      death within 7 days of age was reduced from 63% in the late-treated infants to
      21% in early-treated infants. Increasing numbers of antenatal steroid doses also
      improved the outcome, especially in the early-treated infants. Six hours after
      randomization mean a/APO2 rose to 0.48 in the early-treated infants compared with
      0.36 in the late-treated. The need of mechanical ventilation before discharge was
      reduced from 68% in the late-treated to 25% in the early-treated infants.
      CONCLUSIONS: Nasal CPAP in combination with early treatment with Curosurf
      significantly improves oxygenation and reduces the subsequent need for mechanical
      ventilation in infants <30 weeks' gestational age with RDS.

PMID- 9925871
TI  - Indications for surfactant therapy--the aAPO2 coming of age.
AB  - Indications for administration of surfactant to infants with established
      respiratory distress syndrome (RDS; rescue therapy) remains an area of continued
      investigation. Current recommendations vary from use in infants who are intubated
      and have an aAPO2 <0.22 to use in infants receiving >/=40% oxygen administered in
      a hood when the PaO2 is <80 TORR (aAPO2 approximately <0.36). This commentary is
      written in response to the article by Verder et al, in this issue of Pediatrics,
      who evaluated early versus late treatment of RDS in 60 preterm infants <30 weeks'
      gestation receiving nasal continuous positive airway pressure (CPAP). Early
      treated infants (aAPO2, 0.22 to 0.35; mean, 0.26) had a lower incidence of
      mechanical ventilation or death (21%) than did late-treated infants (63%), who
      did not receive surfactant treatment until the aAPO2 was <0.22 (0.15 to 0.21;
      mean, 0.16). The authors conclude that although approximately half of infants <30
      weeks' gestation with RDS can be treated with nasal CPAP alone, early treatment
      with surfactant when the aAPO2 is 0.22 to 0.36 reduced significantly the need for
      mechanical ventilation. Limitations of applicability of the study to widespread
      use include determination of PO2 values from transcutaneous measurements, which
      may vary from those obtained from arterial samples and affect significantly aAPO2
      ratios. Likewise, use of nasal CPAP significantly affects oxygenation, and
      interpretation of results cannot be extrapolated to intubated infants or those
      receiving oxygen delivered under a hood. Nonetheless, the use of the aAPO2 ratio
      and early administration of surfactant are supported by this study.

PMID- 9925872
TI  - Regulation of synaptic vesicle fusion by protein kinase C.

PMID- 9925873
TI  - Complementary regulation of anaesthetic activation of human (alpha6beta3gamma2L)
      and Drosophila (RDL) GABA receptors by a single amino acid residue.
AB  - 1. The influence of a transmembrane (TM2) amino acid located at a homologous
      position in human beta1 (S290) and beta3 (N289) GABAA receptor subunits and the
      RDL GABA receptor of Drosophila (M314) upon allosteric regulation by general
      anaesthetics has been investigated. 2. GABA-evoked currents mediated by human
      wild-type (WT) alpha6beta3gamma2L or WT RDL GABA receptors expressed in Xenopus
      laevis oocytes were augmented by propofol or pentobarbitone. High concentrations
      of either anaesthetic directly activated alpha6beta3gamma2L, but not RDL,
      receptors. 3. GABA-evoked currents mediated by human mutant GABAA receptors
      expressing the RDL methionine residue (i.e. alpha6beta3N289Mgamma2L) were
      potentiated by propofol or pentobarbitone with approximately 2-fold reduced
      potency and, in the case of propofol, reduced maximal effect. Conspicuously, the
      mutant receptor was refractory to activation by either propofol or
      pentobarbitone. 4. Incorporation of the homologous GABAA beta1-subunit residue in
      the RDL receptor (i.e. RDLM314S) increased the potency, but not the maximal
      effect, of GABA potentiation by either propofol or pentobarbitone. Strikingly,
      either anaesthetic now activated the receptor, an effect confirmed for propofol
      utilizing expression of WT or mutant RDL subunits in Schnieder S2 cells. At RDL
      receptors expressing the homologous beta3-subunit residue (i.e. RDLM314N) the
      actions of propofol were similarly affected, whereas those of pentobarbitone were
      unaltered. 5. The results indicate that the identity of a homologous amino acid
      affects, in a complementary manner, the direct activation of human
      (alpha6beta3gamma2L) and RDL GABA receptors by structurally distinct general
      anaesthetics. Whether the crucial residue acts as a regulator of signal
      transduction or as a component of an anaesthetic binding site per se is
      discussed.

PMID- 9925875
TI  - Role of M2 domain residues in conductance and gating of acetylcholine receptors
      in developing Xenopus muscle.
AB  - 1. The contributions of specific residues in gamma- and epsilon-subunits to the
      developmental changes in conductance and open time of Xenopus muscle
      acetylcholine receptors (AChRs) were investigated. This study was directed
      primarily at residues in the M2 domains of gamma- and epsilon-subunits; however,
      the results of additional mutations in the extracellular region flanking M2 and
      in the amphipathic region between M3 and M4 are also described. 2. The M2 domains
      of gamma- and epsilon-subunits differ at only three amino acid residues, two of
      which are adjacent to each other and located near the narrowest part of the pore.
      These two residues (NI in gamma, SV in epsilon) were found to be major
      determinants of the difference in conductance and open time of AChRs bearing
      gamma- or epsilon-subunits. 3. Mutation of N to S in the gamma-subunit converted
      the long open time of receptors bearing the gamma-subunit (gamma-AChRs) to the
      brief open time characteristic of receptors bearing an epsilon-subunit (epsilon
      AChRs). Conversely, epsilon-AChRs with SV mutated to NI in the epsilon-subunit
      exhibited a long open time characteristic of gamma-AChRs. 4. Mutation of N to S
      in the gamma-subunit increased the conductance of gamma-AChRs but did not confer
      the full conductance of wild-type epsilon-AChRs. Conversely, mutation of SV to NI
      in the epsilon-subunit reduced the conductance of epsilon-AChRs, but not
      completely to the level of wild-type gamma-AChRs.

PMID- 9925874
TI  - ATP inhibition of KATP channels: control of nucleotide sensitivity by the N
      terminal domain of the Kir6.2 subunit.
AB  - 1. To gain insight into the role of the cytoplasmic regions of the Kir6.2 subunit
      in regulating channel activity, we have expressed the sulphonylurea receptor SUR1
      with Kir6.2 subunits containing systematic truncations of the N- and C-termini.
      Up to 30 amino acids could be truncated from the N-terminus, and up to 36 amino
      acids from the C-terminus without loss of functional channels in co-expression
      with SUR1. Furthermore, Kir6.2DeltaC25 and Kir6. 2DeltaC36 subunits expressed
      functional channels in the absence of SUR1. 2. In co-expression with SUR1, N
      terminal truncations increased Ki,ATP ([ATP] causing half-maximal inhibition of
      channel activity) by as much as 10-fold, accompanied by an increase in the ATP
      insensitive open probability, whereas the C-terminal truncations did not affect
      the ATP sensitivity of co-expressed channels. 3. A mutation in the near C
      terminal region, K185Q, reduced ATP sensitivity of co-expressed channels by
      approximately 30-fold, and on the Kir6.2DeltaN2-30 background, this mutation
      decreased ATP sensitivity of co-expressed channels by approximately 400-fold. 4.
      Each of these mutations also reduced the sensitivity to inhibition by ADP, AMP
      and adenosine tetraphosphate. 5. The results can be quantitatively explained by
      assuming that the N-terminal deletions stabilize the ATP-independent open state,
      whereas the Kir6.2K185Q mutation may alter the stability of ATP binding. These
      two effects are energetically additive, causing the large reduction of ATP
      sensitivity in the double mutant channels.

PMID- 9925876
TI  - N-linked glycosylation sites determine HERG channel surface membrane expression.
AB  - 1. Long QT syndrome (LQT) is an electrophysiological disorder that can lead to
      sudden death from cardiac arrhythmias. One form of LQT has been attributed to
      mutations in the human ether-a-go-go-related gene (HERG) that encodes a voltage
      gated cardiac K+ channel. While a recent report indicates that LQT in some
      patients is associated with a mutation of HERG at a consensus extracellular N
      linked glycosylation site (N629), earlier studies failed to identify a role for N
      linked glycosylation in the functional expression of voltage-gated K+ channels.
      In this study we used pharmacological agents and site-directed mutagenesis to
      assess the contribution of N-linked glycosylation to the surface localization of
      HERG channels. 2. Tunicamycin, an inhibitor of N-linked glycosylation, blocked
      normal surface membrane expression of a HERG-green fluorescent protein (GFP)
      fusion protein (HERGGFP) transiently expressed in human embryonic kidney (HEK
      293) cells imaged with confocal microscopy. 3. Immunoblot analysis revealed that
      N-glycosidase F shifted the molecular mass of HERGGFP, stably expressed in HEK
      293 cells, indicating the presence of N-linked carbohydrate moieties. Mutations
      at each of the two putative extracellular N-linked glycosylation sites (N598Q and
      N629Q) led to a perinuclear subcellular localization of HERGGFP stably expressed
      in HEK 293 cells, with no surface membrane expression. Furthermore, patch clamp
      analysis revealed that there was a virtual absence of HERG current in the N
      glycosylation mutants. 4. Taken together, these results strongly suggest that N
      linked glycosylation is required for surface membrane expression of HERG. These
      findings may provide insight into a mechanism responsible for LQT2 due to N
      linked glycosylation-related mutations of HERG.

PMID- 9925877
TI  - Characteristics of 5-HT-containing chemoreceptor cells of the chicken aortic
      body.
AB  - 1. Voltage-dependent and oxygen-sensitive currents in 5-HT-containing epithelioid
      cells isolated from chicken thoracic aorta were examined using the whole-cell
      patch clamp technique. 5-HT immunoreactive cells were identified with Neutral
      Red. The release of 5-HT from chicken thoracic aorta in the presence of excess
      KCl and veratridine was also examined using HPLC. 2. At a holding potential of 
      70 mV with CsCl pipette solution, depolarizing steps between -30 and +60 mV
      produced inward currents that were blocked by tetrodotoxin (0.2 microM). In the
      presence of tetrodotoxin and BaCl2 (5 mM), depolarizing steps evoked slow inward
      currents that were sensitive to CoCl2 (2 mM). Nifedipine (1 microM) decreased the
      currents to 79.4 +/- 1.7 %, and omega-conotoxin GVIA (1 microM) to 20.2 +/- 3.8
      %. 3. When KCl pipette solution was used, depolarizing potentials positive to -40
      mV caused outward currents that were inhibited by tetraethylammonium chloride.
      The K+ currents evoked by depolarizing steps to +20 mV were reduced to 90.3 +/-
      0.8 % by hypoxia in five out of seven cells. Two cells failed to respond to
      hypoxia. The K+ current response was partly decreased by Neutral Red (20 microM).
      4. Excess KCl (60 mM) and veratridine (30 microM) both caused the release of 5-HT
      from aortic strips. 5-HT outputs induced by both stimuli were partly inhibited by
      nifedipine (1 microM) and by omega-conotoxin GVIA (1 microM), and were abolished
      by these drugs in combination and by extracellular Ca2+ removal. 5. These results
      suggest that epithelioid cells containing 5-HT act as chemoreceptor cells in the
      chicken aortic body, having voltage-dependent Na+, K+, and L- and N-type Ca2+
      channels, and oxygen-sensitive K+ channels.

PMID- 9925878
TI  - Comparison of slow inactivation in human heart and rat skeletal muscle Na+
      channel chimaeras.
AB  - 1. Voltage-gated Na+ channels undergo two types of inactivation in response to
      depolarization. One type, fast inactivation, occurs with a time scale of
      milliseconds. The other, slow inactivation, occurs over seconds to minutes. In
      addition, these two processes appear to be distinct at the molecular level.
      However, the molecular mechanism of Na+ channel slow inactivation is unknown. 2.
      We used patch clamp techniques to study slow inactivation, activation and fast
      inactivation in alpha-subunit cDNA clones for wild-type human heart Na+ channels
      (hH1) and rat skeletal muscle Na+ channels (mu1) transiently expressed in human
      embryonic kidney (HEK) cells. Our experiments showed that the Na+ channel slow
      inactivation phenotype (development, steady state and recovery) differed
      dramatically between hH1 and mu1. Slow inactivation in mu1 had a faster onset, a
      steeper voltage dependence, and was more complete compared with hH1. In addition,
      recovery from slow inactivation was much slower for mu1 than for hH1. Activation
      and fast inactivation kinetics were also different in hH1 and mu1. In hH1, fast
      inactivation was slower and V values of activation and steady-state fast
      inactivation (hthorn ) were more negative than in mu1. 3. To better understand
      the molecular basis of Na+ channel slow inactivation, Na+ channel chimaeras were
      constructed with domains from hH1 and mu1. The slow inactivation phenotype in the
      chimaeras (domains denoted by subscripts) mu1(1)hH1(2,3,4), mu1(1,2)hH1(3,4) and
      mu1(1,2,3)hH1(4) was intermediate compared with that of wild-type. However, the
      chimaera mu1(1)hH1(2,3,4) was more like wild-type hH1, while the chimaeras
      mu1(1,2)hH1(3,4) and mu1(1,2,3)hH1(4) were more similar to wild-type mu1. In the
      chimaeras, activation resembled that of mu1, fast inactivation resembled that of
      hH1, and steady-state fast inactivation fell between that of hH1 and mu1. 4. The
      data demonstrate that all four domains can modulate the Na+ channel slow
      inactivation phenotype. However, domains D1 and D2 may play a more prominent role
      in determining Na+ channel slow inactivation phenotype than D3 and D4. The
      results also support previous conclusions that D3 and D4 (and the D3-D4 linker)
      play an important role in Na+ channel fast inactivation, and that activation may
      require non-equivalent contributions from all four domains.

PMID- 9925880
TI  - Ca2+-independent myosin II phosphorylation and contraction in chicken embryo
      fibroblasts.
AB  - 1. Non-muscle contraction is widely believed to be mediated through Ca2+
      stimulated myosin II regulatory light chain (LC20) phosphorylation, similar to
      the contractile regulation of smooth muscle. However, this hypothesis lacks
      conclusive experimental support. 2. By modulating chicken embryo fibroblast
      cytosolic Ca2+ concentration ([Ca2+]i), we investigated the putative role of
      [Ca2+]i in fetal bovine serum (FBS)-stimulated LC20 phosphorylation and force
      development in these cells. 3. Eliminating the FBS-stimulated rise in [Ca2+]i
      with the Ca2+ chelator BAPTA only partially inhibited FBS-stimulated LC20
      phosphorylation and did not significantly alter the magnitude of FBS-stimulated
      isometric contraction. 4. Ionomycin (1 microM) produced a larger but shorter
      lasting rise in [Ca2+]i relative to FBS. However, ionomycin only stimulated a
      small and transient increase in LC20 phosphorylation and did not cause
      contraction. 5. We conclude that fibroblasts differ from smooth muscle in that
      LC20 phosphorylation and contraction are predominantly regulated independently of
      [Ca2+]i.

PMID- 9925879
TI  - Inhibition of volume-regulated anion channels by expression of the cystic
      fibrosis transmembrane conductance regulator.
AB  - 1. To investigate whether the cystic fibrosis transmembrane conductance regulator
      (CFTR) interacts with volume regulated anion channels (VRACs), we measured the
      volume-activated chloride current (ICl,swell) using the whole-cell patch-clamp
      technique in calf pulmonary artery endothelial (CPAE) cells and in COS cells
      transiently transfected with wild-type (WT) CFTR and the deletion mutant
      DeltaF508 CFTR. 2. ICl,swell was significantly reduced in CPAE cells expressing
      WT CFTR to 66.5 +/- 8.8 % (n = 13; mean +/- s. e.m.) of the control value (n =
      11). This reduction was independent of activation of the CFTR channel. 3.
      Expression of DeltaF508 CFTR resulted in two groups of CPAE cells. In the first
      group IBMX and forskolin could activate a Cl- current. In these cells ICl,swell
      was reduced to 52.7 +/- 18.8 % (n = 5) of the control value (n = 21). In the
      second group IBMX and forskolin could not activate a current. The amplitude of
      ICl,swell in these cells was not significantly different from the control value
      (112.4 +/- 13.7 %, n = 11; 21 control cells). 4. Using the same method we showed
      that expression of WT CFTR in COS cells reduced ICl,swell to 62.1 +/- 11.9 % (n =
      14) of the control value (n = 12) without any changes in the kinetics of the
      current. Non-stationary noise analysis suggested that there is no significant
      difference in the single channel conductance of VRAC between CFTR expressing and
      non-expressing COS cells. 5. We conclude that expression of WT CFTR down
      regulates ICl, swell in CPAE and COS cells, suggesting an interaction between
      CFTR and VRAC independent of activation of CFTR.

PMID- 9925881
TI  - The role of N-, Q- and R-type Ca2+ channels in feedback inhibition of ACh release
      from rat basal forebrain neurones.
AB  - 1. The Ca2+ channel subtypes controlling ACh release from basal forebrain
      neurones and the ionic basis underlying muscarinic receptor-mediated
      autoinhibition were studied using skeletal myoballs to detect ACh release from
      individual rat basal forebrain neurones in culture. 2. Somatic Ca2+ currents
      evoked using a simulated action potential waveform revealed that Ca2+ entry was
      primarily through N-, Q- and to a lesser extent R-, T- and L-type Ca2+ channels.
      3. Muscarine (10 microM) inhibited N- and Q- but not R-, T- or L-type somatic
      Ca2+ channels. Agonist inhibition was totally blocked by pre-treatment with
      pertussis toxin (500 ng ml-1). 4. ACh release from discrete sites along basal
      forebrain neurites (1. 2 mM extracellular Ca2+) could be largely abolished by
      blocking Ca2+ entry through either N-type or Q-type Ca2+ channels. Inhibition of
      Ca2+ entry through L- or T-type channels had no effect upon release. Following
      inhibition of either N- or Q-type Ca2+ channels, release could be restored to
      near control levels by raising [Ca2+]o. After selectively blocking N-, Q-, L- and
      T-type channels, low levels of release could still be evoked as a result of Ca2+
      entry through R-type Ca2+ channels. 5. Muscarinic receptor activation reversibly
      inhibited ACh release due to Ca2+ entry through N-, Q- and R-type Ca2+ channels.
      In contrast, inhibition of inwardly rectifying K+ channels using Ba2+ (3-10
      microM) or substance P (0.03-0.1 microM), or block of SK or BK Ca2+-activated K+
      channels with apamin (100 nM) or charbydotoxin (100 nM) respectively, had no
      effect upon either ACh release or its modulation by muscarinic agonists. 6. These
      results show that ACh release from individual release sites on basal forebrain
      neurones is controlled by multiple Ca2+ channel subtypes with overlapping Ca2+
      microdomains and that autoinhibition of release results from M2 muscarinic
      receptor-mediated inhibition of these presynaptic Ca2+ channels rather than as a
      consequence of K+ channel activation.

PMID- 9925882
TI  - The role of sarcolemmal Ca2+-ATPase in the regulation of resting calcium
      concentration in rat ventricular myocytes.
AB  - 1. The aim of this work was to investigate the role of sarcolemmal Ca2+-ATPase in
      rat ventricular myocytes. We have measured intracellular Ca2+ concentration
      ([Ca2+]i) using indo-1. The actions of the ATPase inhibitor carboxyeosin were
      studied. 2. Carboxyeosin increased resting [Ca2+]i and the magnitude of the
      systolic Ca2+ transient and slowed the rate of its relaxation by 5 %. 3.
      Carboxyeosin increased the magnitude of the caffeine-evoked increase in [Ca2+]i
      and slowed its relaxation by 20 %. Removal of extracellular Na+ slowed the rate
      constant by 80 %. When Na+ was removed in a carboxyeosin-treated cell, the
      caffeine-evoked increase in [Ca2+]i did not decay. 4. Carboxyeosin increased the
      integral of the Na+-Ca2+ exchange current activated by caffeine. This is, in
      part, due to an increase in sarcoplasmic reticulum Ca2+ content. 5. When
      extracellular Na+ was removed, there was a transient increase in [Ca2+]i which
      then decayed. The rate of this decay was slowed by carboxyeosin by a factor of
      about four. The residual decay could be abolished with caffeine. 6. In the
      absence of extracellular Na+, increasing extracellular Ca2+ concentration
      ([Ca2+]o) elevated [Ca2+]i. In carboxyeosin-treated cells, [Ca2+]i was much more
      sensitive to [Ca2+]o. 7. These results demonstrate the role of a carboxyeosin
      sensitive Ca2+-ATPase in the control of resting [Ca2+]i and the reduction in
      [Ca2+]i following an increase in [Ca2+]i.

PMID- 9925883
TI  - Calcium oscillations in rhythmically active respiratory neurones in the brainstem
      of the mouse.
AB  - 1. The rhythmically active respiratory network in the brainstem slice of the
      mouse was investigated under in vitro conditions using patch clamp and
      microfluorometric techniques. Rhythmic respiratory activity persisted over the
      whole course of an experiment. 2. Electrophysiologically recorded rhythmic
      activity in respiratory neurones was accompanied by oscillations in intracellular
      calcium, which displayed a maximal concentration of 300 nM and decayed to basal
      levels with a mean time constant of 1.6 +/- 0.9 s. 3. Elevations of calcium
      concentrations were highly correlated with the amplitude of rhythmic membrane
      depolarization of neurones, indicating that they were initiated by a calcium
      influx across the plasma membrane through voltage-gated calcium channels. 4.
      Voltage clamp protocols activating either high voltage-activated (HVA) or both
      HVA and low voltage-activated (LVA) calcium channels showed that intracellular
      calcium responses were mainly evoked by calcium currents through HVA channels. 5.
      Somatic calcium signals depended linearly on transmembrane calcium fluxes,
      suggesting that calcium-induced calcium release did not substantially contribute
      to the response. 6. For calcium elevations below 1 microM, decay time constants
      were essentially independent of the amplitude of calcium rises, indicating that
      calcium extrusion was adequately approximated by a linear extrusion mechanism. 7.
      Cytosolic calcium oscillations observed in neurones of the ventral respiratory
      group provide further evidence for rhythmic activation of calcium-dependent
      conductances or second messenger systems participating in the generation and
      modulation of rhythmic activity in the central nervous system.

PMID- 9925884
TI  - Early metabolic inhibition-induced intracellular sodium and calcium increase in
      rat cerebellar granule cells.
AB  - 1. Possible mechanisms responsible for the increases in intracellular calcium
      ([Ca2+]i) and sodium ([Na+]i) levels seen during metabolic inhibition were
      investigated by continuous [Ca2+]i and [Na+]i measurement in cultured rat
      cerebellar granule cells. An initial small mitochondrial Ca2+ release was seen,
      followed by a large influx of extracellular Ca2+. A large influx of extracellular
      Na+ was also seen. 2. The large [Ca2+]i increase was not due to opening of
      voltage-dependent or voltage-independent calcium channels, activation of NMDA/non
      NMDA channels, activation of the Na+i-Ca2+o exchanger, or inability of
      plasmalemmal Ca2+-ATPase to extrude, or mitochondria to take up, calcium. 3. The
      large [Na+]i increase was not due to activation of the TTX-sensitive Na+ channel,
      the Na+i-Ca2+o exchanger, the Na+-H+ exchanger, or the Na+-K+-2Cl- cotransporter,
      or an inability of Na+-K+-ATPase to extrude the intracellular sodium. 4.
      Phospholipase A2 (PLA2) activation may be involved in the large influx, since
      both were completely inhibited by PLA2 inhibitors. Moreover, melittin (a PLA2
      activator) or lysophosphatidylcholine or arachidonic acid (both PLA2 activation
      products) caused similar responses. Inhibition of PLA2 activity may help prevent
      the influx of these ions that may result in serious brain injury and oedema
      during hypoxia/ischaemia.

PMID- 9925886
TI  - Synergetic activation of outwardly rectifying Cl- currents by hypotonic stress
      and external Ca2+ in murine osteoclasts.
AB  - 1. An outwardly rectifying Cl- (ORCl) current of murine osteoclasts was activated
      by hypotonic stimulation. The current was characterized by rapid activation,
      little inactivation, strong outward rectification, blockage by DIDS and
      permeability to organic acids (pyruvate and glutamate). 2. The hypotonically
      activated ORCl current was inhibited by intracellular dialysis with an ATP-free
      pipette solution, but not by replacement of ATP with a poorly hydrolysable ATP
      analogue adenosine 5'-O-(3-thiotriphosphate). The current amplitude was reduced
      when intracellular alkalinity increased over the pH range 6.6-8.0. 3.
      Intracellular application of cytochalasin D occasionally activated the ORCl
      current without hypotonic stress, but inhibited activation of the ORCl current by
      hypotonic stimulation. The hypotonically activated ORCl current was unaffected by
      a non-actin-depolymerizing cytochalasin, chaetoglobosin C, but partially
      inhibited by deoxyribonuclease I. 4. Removal of extracellular Ca2+ inhibited
      activation of the ORCl current by hypotonic shock, but did not reduce the current
      once activated. The hypotonically activated ORCl current was partially decreased
      by intracellular dialysis with 20 mM EGTA. 5. With 10 mM Ca2+ in the
      extracellular medium, the ORCl current was activated in response to more minor
      decreases in osmolarity than with 1 mM Ca2+. The increased sensitivity to
      hypotonicity was mimicked by increasing the intracellular Ca2+ level (pCa 6.5).
      6. These results suggest that hypotonic stimulation and a rise in the
      extracellular Ca2+ level synergistically activate the ORCl channel of murine
      osteoclasts, and that the activating process is modified by multiple
      intracellular factors (pH, ATP and actin cytoskeletal organization).

PMID- 9925885
TI  - Na+-Ca2+ exchange and its implications for calcium homeostasis in primary
      cultured rat brain microvascular endothelial cells.
AB  - 1. The role of Na+-Ca2+ exchange in the regulation of the cytosolic free Ca2+
      concentration ([Ca2+]i) was studied in primary cultured rat brain capillary
      endothelial cells. [Ca2+]i was measured by digital fluorescence imaging in cells
      loaded with fura-2. 2. ATP (100 microM) applied for a short period of time (6 s)
      caused a rise in [Ca2+]i from 127 +/- 3 (n = 290) to 797 +/- 25 nM, which then
      declined to the resting level, with a t time required for [Ca2+]i to decline to
      half of peak [Ca2+]i) of 5.4 +/- 0.09 s. This effect was independent of external
      Ca2+ and could be abolished by previously discharging the Ca2+ pool of the
      endoplasmic reticulum with thapsigargin (1 microM). 3. Application of
      thapsigargin (1 microM) or cyclopiazonic acid (10 microM) to inhibit the Ca2+
      ATPase of the endoplasmic reticulum 6 s prior to ATP application did not
      influence the peak [Ca2+]i but greatly reduced the rate of decline of [Ca2+]i,
      with t values of 15 +/- 1.6 and 23 +/- 3 s, respectively. 4. In the absence of
      external Na+ (Na+ replaced by Li+ or N-methylglucamine) the basal [Ca2+]i was
      slightly elevated (152 +/- 6 nM) and the restoration of [Ca2+]i after the ATP
      stimulation was significantly slower (t , 7.3 +/- 0.46 s in Li+ medium, 8.12 +/-
      0.4 s in N-methylglucamine medium). 5. The external Na+-dependent component of
      the [Ca2+]i sequestration was also demonstrated in cells stimulated by ATP
      subsequent to addition of cyclopiazonic acid; in a Na+-free medium [Ca2+]i
      remained at the peak level in 88 % of the cells after stimulation with ATP. 6.
      Addition of monensin (10 microM) in the presence of external Na+ increased the
      resting [Ca2+]i to 222 +/- 9 nM over approximately 1 min and subsequent removal
      of extracellular sodium resulted in a further increase in [Ca2+]i to a peak of
      328 +/- 11 nM, which was entirely dependent on external Ca2+. 7. These findings
      indicate that a functional Na+-Ca2+ exchanger is present at the blood-brain
      barrier, which plays a significant role in shaping the stimulation-evoked [Ca2+]i
      signal and is able to work in reverse mode under pharmacological conditions.

PMID- 9925887
TI  - Protein kinase C potentiates transmitter release from the chick ciliary
      presynaptic terminal by increasing the exocytotic fusion probability.
AB  - 1. The giant presynaptic terminal of chick ciliary ganglion was used to examine
      how protein kinase C (PKC) modulates neurotransmitter release. Cholinergic
      excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage
      clamp. 2. Although the EPSC was potentiated by phorbol ester (phorbol 12
      myristate 13-acetate, PMA; 0.1 microM) in a sustained manner, the nicotine
      induced current was unaffected. PMA increased the quantal content to 2.4 +/- 0.4
      (n = 9) of control without changing the quantal size. 3. The inactive isoform of
      PMA, 4alpha-PMA, showed no significant effect on EPSCs. The PMA-induced
      potentiation was antagonized by two PKC inhibitors with different modes of
      action, sphingosine (20 microM) and bisindolylmaleimide I (10 microM). 4. When
      stimulated by twin pulses of short interval, the second EPSC was on average
      larger than the first EPSC (paired-pulse facilitation; PPF). PMA significantly
      decreased the PPF ratio with a time course similar to that of the potentiation of
      the first EPSC. 5. PMA did not affect resting [Ca2+]i or the action potential
      induced [Ca2+]i increment in the giant presynaptic terminals. 6. The effect of
      PMA was less at 10 mM [Ca2+]o than at 1 mM [Ca2+]o. 7. When a train of action
      potentials was generated with a short interval, the EPSC was eventually depressed
      and reached a steady-state level. The recovery process followed a simple
      exponential relation with a rate constant of 0.132 +/- 0.029 s-1. PMA did not
      affect the recovery rate constant of EPSCs from tetanic depression. In addition,
      PMA did not affect the steady-state EPSC which should be proportional to the
      refilling rate of the readily releasable pool of vesicles. 8. These results
      conflict with the hypothesis that PKC upregulates the size of the readily
      releasable pool or the number of release sites. PKC appears to upregulate the
      Ca2+ sensitivity of the process that controls the exocytotic fusion probability.

PMID- 9925888
TI  - The kinetics of exocytosis and endocytosis in the synaptic terminal of goldfish
      retinal bipolar cells.
AB  - 1. The kinetics of exocytosis and endocytosis were studied in the giant synaptic
      terminal of depolarizing bipolar cells from the goldfish retina. Two techniques
      were applied: capacitance measurements of changes in membrane surface area, and
      fluorescence measurements of exocytosis using the membrane dye FM1-43. 2. Three
      phases of exocytosis occurred during maintained depolarization to 0 mV. The first
      component was complete within about 10 ms and involved a pool of 1200-1800
      vesicles (with a total membrane area equivalent to about 1.6 % of the surface of
      the terminal). The second component of exocytosis involved the release of about
      4400 vesicles over 1 s. The third component of exocytosis was stimulated
      continuously at a rate of about 1000 vesicles s-1. 3. After short depolarizations
      (< 200 ms), neither the FM1-43 signal nor the capacitance signal continued to
      rise, indicating that exocytosis stopped rapidly after closure of Ca2+ channels.
      The fall in capacitance could therefore be used to monitor endocytosis
      independently of exocytosis. The capacitance measured after brief stimuli began
      to fall immediately, recovering to the pre-stimulus baseline with a rate constant
      of 0.8 s-1. 4. The amount of exocytosis measured using the capacitance and FM1-43
      techniques was similar during the first 200 ms of depolarization, suggesting that
      the most rapidly released vesicles could be detected by either method. 5. After a
      few seconds of continuous stimulation, the net increase in membrane surface area
      reached a plateau at about 5 %, even though continuous exocytosis occurred at a
      rate of 0.9 % s-1. Under these conditions of balanced exocytosis and endocytosis,
      the rate constant of endocytosis was about 0.2 s-1. The average rate of
      endocytosis during maintained depolarization was therefore considerably slower
      than the rate observed after a brief stimulus. 6. After longer depolarizations (>
      500 ms), both the capacitance and FM1-43 signals continued to rise for periods of
      seconds after closure of Ca2+ channels. The continuation of exocytosis was
      correlated with a persistent increase in [Ca2+]i in the synaptic terminal, as
      indicated by the activation of a Ca2+-dependent conductance and measurements of
      [Ca2+]i using the fluorescent indicator furaptra. 7. The delayed fall in membrane
      capacitance after longer depolarizations occurred along a double exponential time
      course indicating the existence of two endocytic processes: fast endocytosis,
      with a rate constant of 0.8 s-1, and slow endocytosis, with a rate constant of
      0.1 s-1. 8. Increasing the duration of depolarization caused an increase in the
      fraction of membrane recovered by slow endocytosis. After a 100 ms stimulus, all
      the membrane was recycled by fast endocytosis, but after a 5 s depolarization,
      about 50 % of the membrane was recycled by slow endocytosis. 9. These results
      demonstrate the existence of fast and slow endocytic mechanisms at a synapse and
      support the idea that prolonged stimulation leads to an increase in the amount of
      membrane retrieved by the slower route. The rise in cytoplasmic Ca2+ that
      occurred during longer depolarizations was correlated with stimulation of
      continuous exocytosis and inhibition of fast endocytosis. The results also
      confirm that transient and continuous components of exocytosis coexist in the
      synaptic terminal of depolarizing bipolar cells.

PMID- 9925889
TI  - Local facilitation of plateau potentials in dendrites of turtle motoneurones by
      synaptic activation of metabotropic receptors.
AB  - 1. The spatial distribution of synaptic facilitation of plateau potentials in
      dendrites of motoneurones was investigated in transverse sections of the spinal
      cord of the turtle using differential polarization by applied electric fields. 2.
      The excitability of motoneurones in response to depolarizing current pulses was
      increased following brief activation of either the dorsolateral funiculus (DLF)
      or the medial funiculus (MF) even when synaptic potentials were eliminated by
      antagonists of ionotropic receptors. 3. The medial and lateral compartments of
      motoneurones were differentially polarized by the electric field generated by
      passing current between two electrodes on either side of the preparation. In one
      direction of the field lateral dendrites were depolarized while the cell body and
      medial dendrites were hyperpolarized (S- configuration). With current in the
      opposite direction the cell body and medial dendrites were depolarized while
      lateral dendrites were hyperpolarized (S + configuration). 4. Following brief
      activation of the DLF the excitability and the generation of plateau potentials
      were facilitated during differential depolarization of the lateral dendrites but
      not during differential depolarization of the cell body and medial dendrites.
      Following brief activation of the MF the excitability and generation of plateau
      potentials were facilitated during differential depolarization of the cell body
      and medial dendrites but not during differential depolarization of the lateral
      dendrites. 5. It is concluded that the synaptic facilitation of the
      dihydropyridine-sensitive response to depolarization is compartmentalized in
      turtle motoneurones.

PMID- 9925890
TI  - Age-dependent, steroid-specific effects of oestrogen on long-term potentiation in
      rat hippocampal slices.
AB  - 1. Long-term potentiation (LTP) of hippocampal population spike responses and
      excitatory postsynaptic potentials (EPSPs) from area CA1 stratum pyramidale was
      induced in slices of rat hippocampus maintained in vitro following brief high
      frequency stimulation (HFS) of the Schaffer collateral-commissural pathway. When
      administered to slices prior to HFS, 17beta-oestradiol (OE2), at a concentration
      as low as 0.1 nM, suppressed the magnitude of the resultant HFS-induced
      potentiation in slices from prepubertal animals (3 and 4 weeks old) of both
      sexes. 2. OE2 did not suppress the induction of LTP in slices taken from the
      hippocampus of adult animals of either sex. 3. There was no similar suppressant
      effect of 17alpha-oestradiol (OE1), progesterone (PRG) or testosterone (TST) on
      LTP in the young animals, even at a concentration 100 times greater than was
      effective for OE2. 4. The anti-oestrogen compound tamoxifen (TMX; 1.0 and 10.0
      microM), which acts principally at intracellular binding sites within the
      nucleus, was without effect in diminishing the suppressant effect of OE2 on LTP
      in slices from young animals. 5. The LTP observed in slices from both 3-week-old
      and adult rats was AP5 sensitive and thus was shown to be dependent on activation
      of NMDA receptors. Results from whole-cell recording experiments suggested that
      OE2 caused the LTP-suppressant effect through an action on NMDA-mediated
      currents. 6. These data suggest an age-dependent and possibly a surface membrane
      receptor-mediated role for oestrogens in modulating the efficacy of input-output
      properties of CA1 neurones produced by HFS during a critical period in
      development.

PMID- 9925891
TI  - Modification of excitation-contraction coupling by 4-chloro-m-cresol in voltage
      clamped cut muscle fibres of the frog (R. pipiens).
AB  - 1. The effect of 5 microM 4-chloro-m-cresol (4-CmC) on voltage-controlled Ca2+
      release was studied in cut muscle fibres of the frog loaded with internal
      solutions containing 15 mM EGTA. Fibres were voltage clamped using a double
      Vaseline gap system, and Ca2+ signals were recorded with the fluorescent
      indicator dye fura-2 2. Resting intracellular free Ca2+ concentration increased
      from 61 to 100 nM upon application of 4-CmC. 3. Both peak rate of release of
      intracellularly stored Ca2+ and the steady level attained after 50 ms of
      depolarization increased, but the potentiation of the latter was more pronounced
      (by a factor of 1.7 versus 1.3). The voltage of half-maximal activation remained
      unchanged. 4. Non-linear intramembranous charge movements showed no significant
      change in voltage dependence while the maximal charge displaced by depolarization
      increased by 25 %. 5. The dependence of peak release flux on total
      intramembranous charge was not different in 4-CmC, but for the steady level of
      release the steepness of the relation increased by a factor of 1.3. 6. The
      stimulating effect of 5 microM 4-CmC on depolarization-induced Ca2+ release
      resembled the potentiation by 0.5 mM caffeine. However, 0.5 mM caffeine increased
      the peak and steady levels of the release rate by a similar factor and caused no
      increase in the resting free calcium concentration, indicating different modes of
      action of the two substances. 7. Neither 5 microM 4-CmC nor 0.5 mM caffeine led
      to a loss of voltage control of Ca2+ release during repolarization after short
      depolarizations, as has been reported previously for caffeine. Potentiated Ca2+
      release could be terminated by repolarization as fast as under control conditions
      both with 15 mM and 0.1 mM internal EGTA. 8. The effects of 4-CmC may result from
      a direct opening of the release channel combined with an enhancement of the
      transduction mechanism that couples channel opening to displacement of voltage
      sensor charges.

PMID- 9925892
TI  - Adrenergic and vasopressinergic contributions to the cardiovascular response to
      acute hypoxaemia in the llama fetus.
AB  - 1. The effects of fetal intravenous treatment with phentolamine or a
      vasopressinergic V1-receptor antagonist on the fetal cardiovascular responses to
      acute hypoxaemia in the llama were investigated. 2. Six llama fetuses were
      surgically prepared between 60 and 70 % of gestation under general halothane
      anaesthesia with vascular catheters and transit-time ultrasonic flow probes
      around a carotid artery and a femoral artery. At least 4 days after surgery all
      fetuses were subjected to a 3 h experiment: 1 h of normoxia, 1 h of hypoxaemia
      and 1 h of recovery while on slow i.v. infusion with saline. On separate days
      this experiment was repeated with fetal i.v. treatment with either phentolamine
      or a V1-receptor antagonist dissolved in saline. 3. During saline infusion all
      llama fetuses responded to acute hypoxaemia with intense femoral
      vasoconstriction. Phentolamine during normoxia produced hypotension, tachycardia
      and vasodilatation in both the carotid and the femoral circulations. During
      hypoxaemia, fetuses treated with phentolamine did not elicit the pronounced
      femoral vasoconstriction and all died within 20 min of the onset of hypoxaemia. A
      V1-receptor antagonist produced a femoral vasodilatation during normoxia but did
      not affect the fetal cardiovascular responses to acute hypoxaemia. 4. In
      conclusion, alpha-adrenergic and V1-vasopressinergic mechanisms contribute to a
      basal vasoconstrictor tone in the femoral circulation in the llama fetus. The
      enhanced femoral vasoconstriction during acute hypoxaemia in the llama fetus is
      not mediated by stimulation of V1-vasopressin receptors, but is dependent on
      alpha-adrenergic receptor stimulation. Such alpha-adrenergic efferent mechanisms
      are indispensable to fetal survival during hypoxaemia in the llama since their
      abolition leads to cardiovascular collapse and death.

PMID- 9925893
TI  - Hyperoxia and local organ blood flow in the developing chick embryo.
AB  - 1. Hyperoxia can cause local vasoconstriction in adult animal organs as a
      protective mechanism against hyperoxia-induced toxicity. It is not known at what
      time during development this vasoconstrictor capacity is present. Therefore, we
      measured the cardiac output (CO) distribution in different organs during a period
      of acute hyperoxia (100 % O2) in the developing chick embryo. 2. Fertile eggs
      were divided into five incubation time groups (10 and 11, 12 and 13, 14 and 15,
      16 and 17, and 18 and 19 days of a normal incubation time of 21 days). Eggs were
      opened at the air cell and a catheter was inserted into a branch of the
      chorioallantoic vein for injections of 15 microm fluorescent microspheres during
      normoxia and at the end of 5 min (test group 1; n = 39) or 20 min (test group 2;
      n = 21) of hyperoxia exposure (100 % O2). The fraction of CO to an organ was
      calculated as the fluorescence of the organ sample divided by the sum of the
      fluorescence of all organs. 3. Only in 18- and 19-day-old embryos did hyperoxia
      cause a decrease in the fractions of CO to the heart and carcass, and an increase
      in those to the yolk-sac and chorioallantoic membrane. This response was more
      pronounced after 20 min (test group 2) than after 5 min (test group 1) of
      hyperoxia with an additional decrease in the fractions of CO to the brain,
      intestine and liver (test group 2). 4. These data indicate that local mechanisms
      for hyperoxia-induced vasoconstriction in the heart, brain, liver, intestine and
      carcass develop late, during the final 15 % of the incubation period, in the
      developing chick embryo.

PMID- 9925894
TI  - Cardiopulmonary baroreflex inhibition of sympathetic nerve activity is preserved
      with age in healthy humans.
AB  - 1. We tested the hypothesis that the ability of the cardiopulmonary baroreflex to
      produce sympathoinhibition is reduced with age in humans. Eleven young (23 +/- 1
      years, mean +/- s.e.m.) and ten older (64 +/- 1) healthy adult males were studied
      under supine conditions (control) and in response to cardiopulmonary baroreflex
      stimulation evoked by acute central circulatory hypervolaemia (10 deg head-down
      tilt). The two groups were normotensive and free of overt cardiovascular disease.
      2. Supine baseline (control) levels of efferent muscle sympathetic nerve activity
      (MSNA) burst frequency were twice as high in the older men (41 +/- 2 vs. 21 +/- 2
      bursts min-1, P < 0.05). In both groups in response to head-down tilt arterial
      blood pressure and heart rate were unchanged, peripheral venous pressure (PVP)
      increased (P < 0.05), MSNA total activity decreased (P < 0.05), antecubital
      venous plasma noradrenaline concentrations did not change significantly, and
      forearm blood flow and vascular conductance increased (vascular resistance
      decreased) (all P < 0.05). The mean absolute DeltaMSNA/DeltaPVP was similar in
      the young and older men, although the higher control levels of MSNA in the older
      men resulted in a smaller percentage DeltaMSNA/DeltaPVP (P < 0.05). Per DeltaPVP,
      the reduction in forearm vascular resistance was smaller in the older men, but
      there were no age group differences when expressed as increases in forearm
      vascular conductance. 3. These results indicate that the ability of the
      cardiopulmonary baroreflex to inhibit MSNA is well preserved with age in healthy
      adult humans. As such, these findings are not consistent with the concept that
      this mechanism plays a role in the age-associated elevation in basal MSNA.

PMID- 9925895
TI  - Role of adenosine in regulating glucose uptake during contractions and hypoxia in
      rat skeletal muscle.
AB  - 1. The effect of A1-adenosine receptor antagonism via 8-cyclopentyl-1,3-dipropyl
      xanthine (CPDPX) on the stimulation of skeletal muscle glucose uptake by
      contractions and hypoxia was investigated in isolated perfused rat hindquarters.
      The standard perfusate contained either no insulin or a submaximal insulin
      concentration at 100 microU ml-1. 2. Muscles were stimulated to contract for 45
      min by intermittent tetanic stimulation of the sciatic nerve. Hypoxia was induced
      by reducing perfusate haematocrit from 30% to 10% on the one hand, and by
      switching the gassing of the perfusate from a 35% to a 0% O2 mixture for 60 min
      on the other hand. The effect of contractions and hypoxia alone, or in
      combination, was investigated. 3. Hypoxia-induced muscle glucose uptake was not
      altered by CPDPX in the absence or presence of insulin. In contrast, contraction
      induced glucose uptake was reduced by approximately 25 % (P < 0.05) by exposure
      of muscles to CPDPX. CPDPX did not affect hindlimb glucose uptake either before
      or after contractions. 4. The increment of muscle glucose uptake during hypoxia
      combined with contractions was greater (P < 0.05) than the effect of hypoxia
      alone. 5. The current findings provide evidence that the mechanism by which
      hypoxia stimulates muscle glucose uptake is, at least in part, different from the
      mechanism of glucose uptake stimulation by contractions, because (i) A1-adenosine
      receptors regulate insulin-mediated glucose uptake in muscle during contractions
      but not during hypoxia and (ii) submaximal hypoxia and contractions are additive
      stimuli to muscle glucose uptake.

PMID- 9925896
TI  - Early changes in performance, blood flow and capillary fine structure in rat fast
      muscles induced by electrical stimulation.
AB  - 1. Muscle blood flow, capillary fine structure and performance were investigated
      in the early stages of chronic indirect electrical stimulation of ankle flexors
      in the rat. 2. The fast muscles tibialis anterior (TA), extensor digitorum longus
      (EDL) and extensor hallucis proprius (EHP) were unilaterally stimulated via the
      right common peroneal nerve at 10 Hz and supramaximal voltage for 8 h a day for
      2, 3 or 7 days and compared with muscles from control animals. 3. Muscle blood
      flow (MBF) was estimated at rest and during contractions by radioactive
      microspheres. It was higher at rest than in unstimulated controls only in muscles
      stimulated for 2 days; during contractions it was higher in some muscles
      stimulated for 3 days than in controls, and in all muscles by 7 days (192 +/- 17
      vs. 149 +/- 12 ml (100 g)-1min-1 in controls). 4. Electron microscopical
      evaluation of individual capillaries in EHP fixed by superfusion in situ revealed
      thickening of capillary endothelium and decreased lumen volume in muscles
      stimulated for 7 (P < 0.005) but not 3 days. Significantly smaller capillary size
      indicates the presence of newly formed capillaries. 5. Isometric twitch tension,
      recorded from combined TA and EDL in stimulated and contralateral legs during 5
      min contractions at 4 Hz, gradually declined from 175 +/- 9 to 99 +/- 4 kN m-2
      after 7 days of stimulation (P < 0.05) while the fatigue index, calculated as
      (final twitch tension/peak twitch tension) x 100, increased from 69.8 +/- 3.4 to
      90 +/- 3.0 % (P < 0. 05). No significant changes in the fatigue index occurred in
      muscles stimulated for 2 or 3 days. 6. Lower peak tension, but not fatigue index
      or MBF, was also observed in muscles contralateral to those stimulated for 3 and
      7 days, which thus do not represent appropriate controls. 7. We conclude that the
      high resting blood flow found in muscles stimulated for 2 days may initiate the
      capillary growth reported previously, while the relatively modest increase in MBF
      during contractions in muscles that had been stimulated for 7 days may be due to
      increased capillary supply. Swelling of the capillary endothelium and decreased
      volume of the capillary lumen may result in an increased proportion of time spent
      by red blood cells in capillaries, which would improve oxygen extraction.

PMID- 9925897
TI  - The role of prostaglandins in the bradykinin-induced activation of serosal
      afferents of the rat jejunum in vitro.
AB  - 1. This study was performed to elucidate the role of prostaglandins in the action
      of bradykinin on serosal afferent neurones supplying the rat jejunum.
      Extracellular recordings of multi-unit activity were made from serosal afferents
      in isolation, using a novel in vitro preparation. The discharge of single
      afferents within the multi-unit recording was monitored using waveform
      discrimination software. 2. All afferents tested were both mechano- and capsaicin
      sensitive. Application of bradykinin elicited increases in whole nerve discharge
      in a concentration-dependent manner. The agonist potency estimate (EC50) was 0.62
      +/- 0.12 microM and is consistent with an interaction at the B2 receptor subtype.
      3. The stimulatory effect of bradykinin on serosal afferents was antagonized by a
      specific antagonist of the B2 receptor, HOE140. In contrast, a selective B1
      receptor antagonist, [des-Arg10]HOE140, had no effect. The IC50 estimate obtained
      for HOE140 was 1.6 nM and again consistent with an interaction at B2 receptors.
      4. The response to a submaximal concentration of bradykinin (1 microM) was
      significantly reduced to 24.4 +/- 54.9 % of control following blockade of cyclo
      oxygenase activity with naproxen (10 microM). The addition of 1 microM
      prostaglandin E2 (PGE2), in the presence of naproxen, had no direct effect on
      afferent activity, but fully restored the response to bradykinin in 15 single
      afferents. 5. In summary, bradykinin stimulates serosal afferents by a direct
      action on kinin B2 receptors that are present on serosal afferent terminals. The
      response to bradykinin is dependent on the presence of prostaglandins,
      particularly PGE2. We suggest that bradykinin has a self-sensitizing action,
      whereby it stimulates the release of PGE2, which in turn sensitizes the endings
      of serosal afferent neurones responsive to bradykinin.

PMID- 9925898
TI  - Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans.
AB  - 1. The present study investigates to what extent and by which time course
      prolonged strenuous exercise influences the plasma concentration of pro
      inflammatory and inflammation responsive cytokines as well as cytokine inhibitors
      and anti-inflammatory cytokines. 2. Ten male subjects (median age 27.5 years,
      range 24-37) completed the Copenhagen Marathon 1997 (median running time 3 : 26
      (h : min), range 2 : 40-4 : 20). Blood samples were obtained before, immediately
      after and then every 30 min in a 4 h post-exercise recovery period. 3. The plasma
      concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL
      6, IL-1ra, sTNF-r1, sTNF-r2 and IL-10 were measured by enzyme-linked
      immunosorbent assay (ELISA). The highest concentration of IL-6 was found
      immediately after the race, whereas IL-1ra peaked 1 h post exercise (128-fold and
      39-fold increase, respectively, as compared with the pre-exercise values). The
      plasma level of IL-1beta, TNFalpha, sTNF-r1 and sTNF-r2 peaked in the first hour
      after the exercise (2. 1-, 2.3-, 2.7- and 1.6-fold, respectively). The plasma
      level of IL-10 showed a 27-fold increase immediately post exercise. 4. In
      conclusion, strenuous exercise induces an increase in the pro-inflammatory
      cytokines TNFalpha and IL-1beta and a dramatic increase in the inflammation
      responsive cytokine IL-6. This is balanced by the release of cytokine inhibitors
      (IL-1ra, sTNF-r1 and sTNF-r2) and the anti-inflammatory cytokine IL-10. The study
      suggests that cytokine inhibitors and anti-inflammatory cytokines restrict the
      magnitude and duration of the inflammatory response to exercise.

PMID- 9925899
TI  - Oral airway flow dynamics in healthy humans.
AB  - 1. Oral airway resistance (RO) is an important determinant of oro-nasal
      partitioning of airflow (e.g. during exercise and sleep); however, little is
      known of factors influencing its magnitude and measurement. 2. We developed a non
      invasive standardized technique for measuring RO (based on a modification of
      posterior rhinomanometry) and examined inspiratory RO in 17 healthy male subjects
      (age, 36 +/- 2 years (mean +/- s.e.m.); height, 177 +/- 2 cm; weight, 83 +/- 3
      kg). 3. Inspiratory RO (at 0.4 l s-1) was 0.86 +/- 0.23 cmH2O l-1 s-1 during
      resting mouthpiece breathing in the upright posture. RO was unaffected by
      assumption of the supine posture, tended to decrease with head and neck extension
      and increased to 1.22 +/- 0.19 cmH2O l-1 s-1 (n = 10 subjects, P < 0.01) with 40
      45 deg of head and neck flexion. When breathing via a mouth-mask RO was 2.98 +/-
      0.42 cmH2O l-1 s-1 (n = 7) and not significantly different from nasal airway
      resistance. 4. Thus, in awake healthy male subjects with constant jaw position,
      RO is unaffected by body posture but increases with modest degrees of head and
      neck flexion. This influence on upper airway patency may be important when oral
      route breathing is associated with alterations in head and neck position, e.g.
      during sleep.

PMID- 9925900
TI  - Independent control of head and gaze movements during head-free pursuit in
      humans.
AB  - 1. Head and gaze movements are usually highly co-ordinated. Here we demonstrate
      that under certain circumstances they can be controlled independently and we
      investigate the role of anticipatory activity in this process. 2. In experiment
      1, subjects tracked, with head and eyes, a sinusoidally moving target. Overall,
      head and gaze trajectories were tightly coupled. From moment to moment, however,
      the trajectories could be very different and head movements were significantly
      more variable than gaze movements. 3. Predictive head and gaze responses can be
      elicited by repeated presentation of an intermittently illuminated, constant
      velocity target. In experiment 2 this protocol elicited a build-up of
      anticipatory head and gaze velocity, in opposing directions, when subjects made
      head movements in the opposite direction to target movement whilst maintaining
      gaze on target. 4. In experiment 3, head and gaze movements were completely
      uncoupled. Subjects followed, with head and gaze, respectively, two targets
      moving at different, harmonically unrelated frequencies. This was possible when
      both targets were visual, and also when gaze followed a visual target at one
      frequency whilst the head was oscillated in time with an auditory tone modulated
      at the second frequency. 5. We conclude that these results provide evidence of a
      visuomotor predictive mechanism that continuously samples visual feedback
      information and stores it such that it can be accessed by either the eye or the
      head to generate anticipatory movements. This overcomes time delays in visuomotor
      processing and facilitates time-sharing of motor activities, making possible the
      performance of two tasks simultaneously.

PMID- 9925902
TI  - Changes in cerebrospinal fluid monoamine metabolites, tryptophan, and gamma
      aminobutyric acid during the 1st year of life in normal infants. comparison with
      victims of sudden infant death syndrome.
AB  - Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5
      hydroxyindoleacetic acid, homovanillic acid, tryptophan, and gamma-aminobutyric
      acid were measured using high-performance liquid chromatography in 102 infants
      during the 1st year of life (preterm and term neonates included). CSF levels are
      expressed versus corrected age (postnatal days - preterm days) which reflects the
      stage of maturity of the central nervous system. These results are compared to
      those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All
      components were significantly higher in SIDS than in the age-matched control
      group. This increase does not seem to be an artefact related to death. Indeed,
      under the same conditions concerning postmortem time interval before CSF sampling
      and analysis, the levels are not significantly higher in infants who died from a
      known pathology than in living infants. Moreover, in living infants as regards a
      pathology such as asphyxia or hypoventilation in comparison with SIDS, similar
      profiles are observed in some neurotransmitters or metabolites. Other studies are
      necessary to explore further neurotransmission systems in SIDS.

PMID- 9925901
TI  - Insulin modulates cellular proliferation in developing human jejunum and colon.
AB  - Several lines of evidence suggest an important role for insulin in the regulatory
      mechanism of rodent small intestinal development. To investigate its potential
      implication in human gut, the immunofluorescent localization of insulin receptors
      (IR) and the influence of insulin (30 microU or 3 mU/ml) on [3H]-thymidine
      incorporation and on lactase and alkaline phosphatase activities were studied in
      fetal jejunum and colon (14-19 weeks). We demonstrate the early presence of IR,
      mainly detected in the basolateral portion of enterocytes and colonocytes along
      the crypt-villus axis. Insulin increased [3H]-thymidine incorporation as well as
      epithelial labeling indices in cultured explants from jejunum and colon without
      affecting enzymic activities. This study establishes, for the first time, that
      insulin stimulates proliferation of epithelial cells expressing IR in both
      segments without affecting brush border hydrolases in the developing human gut.

PMID- 9925903
TI  - Effect of repeated doses of sucrose during heel stick procedure in preterm
      neonates.
AB  - The purpose of this randomized clinical trial was to test the efficacy of
      repeated versus single dose sucrose to decrease pain from routine heel stick
      procedures in preterm neonates. Infants (n = 48) in the first week of life with a
      mean gestational age of 31 weeks received 0.05 ml of 24% sucrose solution or
      sterile water by mouth (1) 2 min prior to actual lancing of the heel; (2) just
      prior to lancing, and (3) 2 min after lancing. The single-dose group received
      sucrose for the first dose and water for the second and third dose; the repeated
      dose group received sucrose three times, and the placebo group received only
      water. The Premature Infant Pain Profile (PIPP) scores were obtained for five 30
      second blocks from lancing. Both sucrose groups had lower PIPP scores (single
      sucrose pain scores, 6.8-8.2, p = 0.07; repeated sucrose pain scores, 5.3-6. 2, p
      < 0.01) than water (pain scores 7.9-9.1), and in the last block, the repeated
      dose had lower scores than the single dose (6.2 vs. 8. 2, p < 0.05).

PMID- 9925904
TI  - Postnatal changes of leptin levels in full-term and preterm neonates: their
      relation to intrauterine growth, gender and testosterone.
AB  - The present study was carried out to investigate leptin levels in arterial and
      venous cord serum and in amniotic fluid in full-term infants at birth and on the
      5th postnatal day to define the relationship of leptin to intrauterine growth
      rate, gender and early postnatal life. The relation of weight gain to serum
      leptin levels in male preterm infants was determined measuring leptin
      concentration weekly in the first 5 postnatal weeks. Testosterone levels were
      determined simultaneously to explore a possible relationship between leptin and
      testosterone concentrations. Fifty-three term newborn infants with mean birth
      weight and gestational age of 3,419 g (range 2,150-4,480) and 38.9 weeks (range
      36-41) and 19 preterm male infants (mean birth weight and gestational age were
      1,416 g (770-1,800) and 30.2 weeks (26-35) were enrolled into the study. Leptin
      and testosterone levels were determined by radioimmunoassay. It was demonstrated
      that serum leptin levels were markedly elevated in the cord blood without
      discernible arteriovenous differences. Cord blood leptin was found to correlate
      with birth weight (r = 0.40, p < 0.002), weight to length ratio (r = 0.40, p <
      0.002) and body mass index (r = 0.35, p < 0.005). It was significantly lower in
      boys as opposed to girls (p < 0.01) and there was an apparent fall by the 5th
      postnatal day (p < 0.001). Amniotic fluid contained leptin in much less
      concentration than cord blood and it proved to be independent of intrauterine
      growth or gender. Serum leptin concentration in preterm infants at 1 week of age
      was significantly lower compared with term infants (p < 0.002) and it increased
      progressively with age (p < 0.01). An inverse relationship was found between
      leptin and testosterone level (r = -0.358, p < 0.01) and a positive correlation
      between leptin level and weight/height ratio (r = 0.674, p < 0.01). It is
      concluded that leptin derived either from placenta or fetal adipose tissue may be
      involved in regulating fetal growth and development and it may be related to
      energy intake, storage and expenditure. In preterm male infants serum leptin
      concentration increases with postnatal weight and testosterone may suppress
      leptin synthesis.

PMID- 9925905
TI  - Some risk factors for cerebral palsy in very premature infants: importance of
      premature rupture of membranes and monochorionic twin placentation.
AB  - OBJECTIVE: To delineate the perinatal risk factors of neurodevelopmental
      disabilities in very preterm birth applying logistic regression analysis. DESIGN:
      This prospective, geographically defined collaborative study was carried out in
      the Franche-Comte region of France. SUBJECTS: From October 1, 1990 to September
      30, 1992, perinatal and follow-up data were collected on 203 consecutive live
      born singleton or twin non-malformed infants with strictly ascertained
      gestational ages of less than 33 weeks. MAIN OUTCOME MEASURE: The rate of
      cerebral palsy and/or severe mental retardation as diagnosed by a family
      physician or pediatrician with a screening-skill test performed at 2 years of
      age. RESULTS: 167/171 (98%) survivors were evaluated. Twenty-two of the 167
      examined infants (13%) showed signs of cerebral palsy, and 10 of these had severe
      cerebral palsy or mental retardation. Risk factors for disabilities were selected
      by a multivariate approach: premature rupture of membranes >/=48 h (OR 4.3, 95%
      CI 1.6-11.8); monochorionic twin placentation (OR 6.0, 95% CI 1.7-21.3), and
      respiratory distress syndrome (OR 2.8, 95% CI 1.1-7.1). CONCLUSION: This
      geographically defined prospective study gives epidemiological data and highly
      suggests that there is a link between prenatal events (premature rupture of
      membranes, monochorionic twin placentation), postnatal events (respiratory
      distress syndrome), and neurological disabilities in former preterm infants.

PMID- 9925906
TI  - Role of nitric oxide in cardiovascular responses to endotoxemia in neonatal
      lambs.
AB  - To determine whether systemic cardiovascular responses to gram-negative
      endotoxemia are mediated by nitric oxide, we evaluated time-dependent changes in
      contractility and hemodynamics in a neonatal sheep model subjected to nitric
      oxide synthesis inhibition with L-Name (Nomega-nitro-L-arginine methyl ester).
      Four groups were studied: control (C), endotoxin (E), endotoxin L-Name where the
      nitric oxide synthase inhibitor was given prior to endotoxin (ELN), and a control
      L-Name group pretreated with L-Name (CLN). The contractility, measured as end
      systolic elastance (Ees), increased transiently in the E group and then returned
      to baseline. In contrast, Ees declined over time in the ELN group. In terms of
      peripheral hemodynamics, both the E and ELN groups demonstrated significant
      progressive decreases in blood pressure and vascular resistance. The results of
      this study suggest that nitric oxide contributes to the newborn contractile
      response of the heart to endotoxin, but does not appear to mediate the systemic
      vascular relaxation response.

PMID- 9925907
TI  - Influence of inhaled nitric oxide and hyperoxia on Na,K-ATPase expression and
      lung edema in newborn piglets.
AB  - This study was undertaken to examine the combined effect of nitric oxide (NO) and
      hyperoxia on lung edema and Na,K-ATPase expression. Newborn piglets were exposed
      to room air (FiO2 = 0.21), room air plus 50 ppm NO, hyperoxia (FiO2 >/= 0.96) or
      to hyperoxia plus 50 ppm NO for 4-5 days. Animals exposed to NO in room air
      experienced only a slight decrease in Na,K-ATPase alpha subunit protein level.
      Hyperoxia, in the absence of NO, induced both the mRNA and the protein level of
      Na,K-ATP-ase alpha subunit and significantly increased wet lung weight,
      extravascular lung water, and alveolar permeability. NO in hyperoxia decreased
      the hyperoxic-mediated induction of Na,K-ATPase alpha subunit mRNA and protein
      while wet lung weight, extravascular lung water, and alveolar permeability
      remained elevated. These results suggest that 50 ppm of inhaled NO may not
      improve hyperoxic-induced lung injury and may interfere with the expression of
      Na,K-ATPase which constitutes a part of the cellular defense mechanism against
      oxygen toxicity.

PMID- 9925908
TI  - Smooth muscle expresses bone morphogenetic protein (Vgr-1/BMP-6) in human fetal
      intestine.
AB  - During human fetal development, autocrine TGF-beta1 regulates the synthesis of
      specific collagen types by intestinal smooth muscle cells in an age-dependent
      manner. Vgr-1/BMP6, a member of the TGF-beta superfamily, modulates epithelial,
      endochondral and neural tissue development in mice: a related peptide is
      essential to gut morphogenesis in Drosophila. This is the first study to detect
      vgr-1/BMP-6 during human intestinal organogenesis. Polyclonal antibodies to the
      precursor and mature fragments of vgr-1 were used in immunohistochemical studies
      of human intestine at 15, 19 and 24 weeks' gestation. Immunoreactivity was
      detected with the antibody directed against the precursor portion of vgr-1. Only
      smooth muscle structures stained for vgr-1 including muscularis propria,
      muscularis mucosa and vasculature. BMP-6 mRNA was detected by RNase protection
      assay in cultured muscle cells from 11, 17 and 22 weeks' gestation. This study
      demonstrates vgr-1/BMP 6 expression in the developing human fetal intestine,
      exclusively in muscle.

PMID- 9925909
TI  - A satellite DNA of the Sparidae family (pisces, perciformes) associated with
      telomeric sequences.
AB  - This paper reports on the isolation and localization of the subtelomeric DraI
      satellite DNA in the Sparidae family. Gene cloning determined that the DraI
      satellite DNA is present in only 3 species (Pagrus pagrus, P. auriga, and
      Pagellus erythrinus) of the 10 Sparidae species analyzed. The results were
      confirmed by PCR amplification. This satellite DNA is located in a subtelomeric
      position in all 48 acrocentric chromosomes of these species. However,
      interstitial loci are also observed. Sequence analysis of monomers of this
      repetitive family indicates that the satellite DNA is associated with telomeric
      sequences, (TTAGGG)n, in at least one species, P. erythrinus. This is the first
      direct demonstration of the existence of the consensus telomere sequences of
      vertebrates in fish. Likewise, this report also demonstrates that the ends of
      fish chromosomes have a structure similar to those of most eukaryote chromosomes,
      viz., telomere sequences and subtelomeric sequences associated by a boundary in
      which both types of sequences are interspersed. The recent origin of the DraI
      satellite DNA and its use as a phylogenetic marker is discussed.

PMID- 9925910
TI  - Assignment1 of CSRP1 encoding the LIM domain protein CRP1, to human chromosome
      1q32 by fluorescence in situ hybridization.

PMID- 9925911
TI  - Assignment1 of the murine Ki-67 gene (Mki67) to chromosome band 7F3-F5 by in situ
      hybridization.

PMID- 9925912
TI  - Assignment1 of a UDP-glucose:ceramide glucosyltransferase gene (Ugcg) to mouse
      chromosome band 4B3 by in situ hybridization.

PMID- 9925913
TI  - Assignment1 of phosphotriesterase-related gene (PTER) to human chromosome band
      10p12 by in situ hybridization.

PMID- 9925914
TI  - Alternative splicing, genomic structure, and fine chromosome localization of
      REV3L.
AB  - We have localized a human homolog, REV3L, of the Saccharomyces cerevisiae REV3
      gene on chromosome region 6q21. The full-length cDNA consists of 10,919
      nucleotides, with a putative open reading frame of 9,159 bp for a predicted
      protein of 3,053 amino acids. The gene contains 33 exons in about 200 kb of
      genomic DNA. In contrast to the previously reported sequence, an additional exon
      and an alternative splicing site are demonstrated.

PMID- 9925915
TI  - Localization of 5-methylcytosine in metaphase chromosomes of diploid and triploid
      pacu fish, Piaractus mesopotamicus (pisces, characiformes).
AB  - The distribution of 5-methylcytosine (5-MeC) was investigated in fish chromosomes
      by indirect immunofluorescence using a highly specific 5-MeC monoclonal antibody.
      Diploid and artificially produced triploid specimens of the pacu fish, Piaractus
      mesopotamicus, were analyzed. The strong immunofluorescent signals were
      coincident with the heterochromatic regions of both diploids and triploids in a
      pattern that matched the C-banding pattern. In the euchromatin, heterogeneous
      labeling was observed along the chromatids. The weakness of this labeling
      hindered comparison of the fluorescence labeling of homologous chromosomes from
      diploid and triploid individuals. However, no striking differences were observed.
      The possibility that the euchromatin labeling by the 5-MeC antibody is related to
      the occurrence of mildly repetitive sequences in the genome of Piaractus is
      discussed.

PMID- 9925916
TI  - Identification, genomic organization, and alternative splicing of KNSL3, a novel
      human gene encoding a kinesin-like protein.
AB  - Proteins of the kinesin superfamily are microtubule-dependent molecular motors
      that play important roles in organelle transport and cell division. Through
      genomic sequencing and use of the RT-PCR technique, we have identified and
      characterized KNSL3 (kinesin-like 3), a novel member of the kinesin-like protein
      family in humans. We determined its genomic organization and detected four
      alternatively spliced transcripts. KNSL3 was expressed ubiquitously, but sizes
      and relative amounts of the major products were different in each of the tissues
      examined. Alternative splicing, along with the multiplicity of genes in the
      molecular family that includes KNSL3, produce diversity among the C-terminal ends
      of kinesins. These observations may contribute to an understanding of the
      specificity of different kinesins with respect to organelle binding.

PMID- 9925917
TI  - Polyclonal expansion of cells with trisomy 7 in synovia from patients with
      osteoarthritis.
AB  - Trisomy 7 as the single chromosome aberration has been found in a variety of
      neoplasms and in normal tissue in the proximity of tumors, as well as in non
      neoplastic lesions. Recently, we described a nonrandom pattern of chromosome
      aberrations, in particular, a gain of chromosome 7, in synovia, cartilage, and
      osteophytes from patients with osteoarthritis. To study the clonal origin of
      trisomy 7 in osteoarthritis, multiple synovial samples were collected from five
      women, all of whom were informative heterozygotes with regard to the X-linked
      human androgen receptor gene (AR). From each case, three to four independent cell
      cultures were initiated. Trisomic cell populations were subcloned from the
      individual cultures, and it was established whether or not the same allele of AR
      was inactivated in trisomic cells from different parts of the same joint. The
      finding of a polyclonal X-inactivation pattern in two of the cases provides
      strong evidence that gain of an extra copy of chromosome 7 occurs independently
      in multiple cells.

PMID- 9925918
TI  - Comparative gene mapping: cytogenetic localization of PROC, EN1, ALPI, TNP1, and
      IL1B in cattle and sheep reveals a conserved rearrangement relative to the human
      genome.
AB  - The cytogenetic locations of the genes for protein C (PROC), transition protein 1
      (TNP1), intestinal alkaline phosphatase (ALPI), engrailed (EN1), and human
      protointerleukin beta (IL1B) have been compared between cattle (Bos taurus, BTA)
      and sheep (Ovis aries, OAR). Bovine YAC and cosmid clones were used as FISH
      probes to determine the order (centromere to telomere) of four of these genes on
      OAR 2q, as well as the location of IL1B on OAR 3p. In cattle, IL1B and EN1 were
      assigned to BTA 11 and BTA 2, respectively. Alignment of the ovine, bovine, and
      human physical maps based on these data shows that segments of conserved synteny
      and chromosomal rearrangements detected between cattle and human are also found
      in sheep, where the order in cattle is conserved.

PMID- 9925919
TI  - Description and physical localization of the bovine survival of motor neuron gene
      (SMN).
AB  - Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease in
      humans and other mammals, characterized by degeneration of anterior horn cells of
      the spinal cord. In humans, the survival of motor neuron gene (SMN) has been
      recognized as the SMA-determining gene and has been mapped to 5q13. In cattle,
      SMA is a recurrent, inherited disease that plays an important economic role in
      breeding programs of Brown Swiss stock. Now we have identified the full- length
      cDNA sequence of the bovine SMN gene. Molecular analysis and characterization of
      the sequence documents 85% identity to its human counterpart and three
      evolutionarily conserved domains in different species. Physical mapping data
      reveals that bovine SMN is localized to chromosome region 20q12-->q13, supporting
      the conserved synteny of this chromosomal region between humans and cattle.

PMID- 9925920
TI  - Assignment of the human cts18.1 gene PSCD2L to chromosome 19 band q13 using a
      radiation hybrid mapping panel.

PMID- 9925921
TI  - Assignment1 of microsomal epoxide hydrolase (EPHX1) to human chromosome 1q42.1 by
      in situ hybridization.

PMID- 9925922
TI  - Identification and assignment of the human transient receptor potential channel 6
      gene TRPC6 to chromosome 11q21-->q22.

PMID- 9925923
TI  - Assignment1 of human PLCB2 encoding PLC beta2 to human chromosome 15q15 by
      fluorescence in situ hybridization.

PMID- 9925924
TI  - Assignment1 of glucose 6-phosphate translocase (G6PT1) to human chromosome band
      11q23.3 by in situ hybridization.

PMID- 9925925
TI  - Subchromosomal assignment1 of the TSSC1 gene to human chromosome band 11p15.5
      near the HBB gene cluster.

PMID- 9925926
TI  - Human DXYS156 of pentanucleotide repeat (TAAAA)n: chromosomal localization by
      somatic hybrid mapping and sequencing analysis.

PMID- 9925927
TI  - Assignment1 of human putative tumor suppressor genes ST13 (alias SNC6) and ST14
      (alias SNC19) to human chromosome bands 22q13 and 11q24-->q25 by in situ
      hybridization.

PMID- 9925928
TI  - Assignment1 of STAT1 to human chromosome 2q32 by FISH and radiation hybrids.

PMID- 9925929
TI  - Differential destabilization of repetitive sequence hybrids in fluorescence in
      situ hybridization.
AB  - A method for painting a chromosome or chromosome region by fluorescence in situ
      hybridization (FISH) without blocking DNA is described. Both unique sequence and
      repetitive sequence components of a fluorescently labeled probe are hybridized
      under low-stringency conditions, but the chromosomes are washed in such a manner
      that repetitive sequences are differentially removed, while region-specific
      unique sequence fragments remain bound to the target chromosomes. We refer to
      this differential retention and removal of probe components as differential
      stability FISH.

PMID- 9925931
TI  - Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4
      band q26 by radiation hybrid mapping.

PMID- 9925930
TI  - Transcription factor effects on chromosome constitution of cell hybrids.
AB  - When immunoglobulin (Ig)-secreting plasmacytomas are fused to a T-cell lymphoma,
      Ig gene expression ceases in greater than 95% of the resulting hybrids. In the
      rare hybrids that continue to express Ig, all other tested B lymphocyte-specific
      genes also remain active. The low frequency with which these Ig-expressing
      hybrids are recovered, along with the fact that cell fusions can lead to
      chromosome loss, led us to propose that this rare phenotype was due to loss of a
      T-cell-derived chromosome encoding a factor or factors with gene silencing
      activity. To identify the relevant chromosome, we have used a polymerase chain
      reaction (PCR)-assisted method of chromosome mapping to analyze both Ig-silenced
      (common) and Ig-expressing (rare) hybrids. Although no single chromosome was
      found to correlate with Ig gene silencing, we discovered that the two types of
      hybrids had undergone distinct patterns of chromosome loss. Moreover, we found
      that ectopic expression of a B-cell-specific transcription factor (Oct-2)
      dramatically altered both the phenotype and chromosome constitution of hybrids
      arising in these cell fusions.

PMID- 9925932
TI  - Assignment1 of the p150 subunit of the eukaryotic initiation factor 3A gene
      (EIF3A) to human chromosome band 10q26 by in situ hybridisation.

PMID- 9925933
TI  - Assignment1 of the bystin gene BYSL to human chromosome band 6p21.1 by in situ
      hybridization.

PMID- 9925934
TI  - Assignment1 of a putative acetyl-CoA transporter gene (Acatn) to mouse chromosome
      band 3E1-E3 by in situ hybridization.

PMID- 9925935
TI  - Assignment1 of the mitochondrial translational initiation factor 2 gene (MTIF2)
      to human chromosome 2 bands p16-->p14 by in situ hybridization and with somatic
      cell hybrids.

PMID- 9925936
TI  - Assignment1 of the E-cadherin gene (CDH1) to chromosome 16q22.1 by radiation
      hybrid mapping.

PMID- 9925937
TI  - Assignment1 of SUPV3L1 to human chromosome band 10q22.1 by in situ hybridization.

PMID- 9925938
TI  - Assignment1 of the CD59 gene to pig chromosome band 2p17-->p14 with somatic cell
      hybrids.

PMID- 9925939
TI  - Assignment1 of cluster of differentiation 1 locus (CD1) to pig chromosome bands
      4q1.5-->q1.6 by in situ hybridization.

PMID- 9925940
TI  - The gene encoding the transcriptional repressor BERF-1 maps to a region of
      conserved synteny on mouse chromosome 16 and human chromosome 3 and a related
      pseudogene maps to mouse chromosome 8.
AB  - We have recently identified and characterized a Kruppel-like zinc finger protein
      (BERF-1), that functions as a repressor of beta enolase gene transcription. By
      interspecific backcross analysis the gene encoding BERF-1 was localized 4.7 cM
      proximal to the Mtv6 locus on mouse chromosome 16, and an isolated pseudogene was
      localized to mouse chromosome 8, about 5.3 cM distal to the D8Mit4 marker.
      Nucleotide sequence identity and chomosome location indicate that the gene
      encoding BERF-1 is the mouse homologue (Zfp148) of ZNF148 localized to human
      chromosome 3q21, a common translocation site in acute myeloid leukemia patients.

PMID- 9925941
TI  - Assignment of the human tumor transforming gene TUTR1 to chromosome band 5q35.1
      by fluorescence in situ hybridization.

PMID- 9925942
TI  - Assignment1 of the gene of mitochondrial branched chain aminotransferase (BCAT2)
      to sheep chromosome band 14q24 and to cattle and goat chromosome bands 18q24 by
      in situ hybridization.

PMID- 9925943
TI  - Assignment1 of the ubiquitin conjugating enzyme gene, UBE2G2, to human chromosome
      band 21q22.3 by in situ hybridization.

PMID- 9925944
TI  - Assignment1 of herpesvirus-associated ubiquitin-specific protease gene HAUSP to
      human chromosome band 16p13.3 by in situ hybridization.

PMID- 9925945
TI  - Cloning and chromosome mapping of the human casein kinase I gamma3 gene
      (CSNK1G3).

PMID- 9925946
TI  - Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and
      neutrophil elastase (Ela2).
AB  - Proteinase-3 (PR-3) and neutrophil elastase (NE) are polymorphonuclear leukocyte
      serine proteinases that degrade extracellular matrix proteins including elastin
      and appear to be involved in the pathogenesis of several diseases characterized
      by tissue destruction most notably emphysema and Wegener's granulomatosis. In
      this report we characterize and compare the mouse PR-3 and NE genes and establish
      by FISH analysis a common location on mouse chromosome 10C2. Each gene consists
      of five exons and four introns conserving the typical granule-associated serine
      proteinase gene structure. The mouse PR-3 gene (Prtn3) is approximately 3.7 kb
      and is within 2.2 kb of the smaller (1.7 kb) NE gene (Ela2). The larger size of
      Prtn3 is accounted for by differences in intron sizes. A comparison between the
      mouse and human PR-3 cDNA reveals 73% homology, however, this drops to 60% when
      the amino acid sequences are compared. Homology between the mouse and human NE
      cDNA is 77% for both the cDNA and amino acid sequences. The catalytic triad and
      its placement are conserved among the four genes. The proximal promoter of mouse
      Prtn3 contains a TATA box, c-myb and an ets transcriptional site. As these are
      functional elements in the mouse Ela2 promoter they may also be important in the
      expression of Prtn3.

PMID- 9925947
TI  - Characterization and chromosome location of the gene GSTZ1 encoding the human
      Zeta class glutathione transferase and maleylacetoacetate isomerase.
AB  - The Zeta class of cytosolic glutathione-S-transferases (GSTs) has recently been
      identified and spans a range of species from plants to humans. The cDNA and
      protein of a human member of this class have been previously characterised in our
      laboratory. This cDNA has also been described as maleylacetoacetate isomerase
      (MAAI), an enzyme of the phenylalanine catabolism pathway (Fernandez-Canon and
      Penalva, 1998). The present study has determined the structure and chromosome
      location of the gene encoding human GSTZ1/MAAI. The gene spans approximately 10.9
      kb and is composed of 9 exons. Three intron positions of GSTZ1 were precisely
      conserved compared to the carnation and Caenorhabditis elegans Zeta GST genes.
      Fluorescent in situ hybridization mapped the gene to a single locus on chromosome
      14q24.3, which is in agreement with an independent localization between the
      Genethon markers D14S263 and D14S67. The coding region of the gene differed from
      the GSTZ1 cDNA at two nucleotide positions in exon 3, resulting in Lys-32-->Glu
      and Arg-42--> Gly substitutions. This gene structure information will allow
      analysis of the polymorphism in genomic DNA samples, and enables further
      investigations into genetic defects in this step of the phenylalanine catabolism
      pathway.

PMID- 9925948
TI  - Rat tenascin-R gene: structure, chromosome location and transcriptional activity
      of promoter and exon 1.
AB  - Tenascin-R is an extracellular matrix protein expressed exclusively in the
      central nervous system where it is thought to play a relevant role in regulating
      neurite outgrowth. We have i) cloned the cDNA of the rat tenascin-R 5' region;
      ii) defined its genomic organization, obtaining the sequence of two novel
      untranslated exons; iii) mapped the gene to rat chromosome 13q23 and suggested a
      previously unreported synteny between rat chromosome 13q23, human chromosome
      1q24, and mouse chromosome 4E; and iv) sequenced and characterized the elements
      responsible for its neural cell-restricted transcription. We found that two
      discrete regions of the rat gene (the first in the proximal promoter, the second
      in the first exon) are independently able to activate to a high degree the
      transcription of a reporter gene in either human or rat neuroblastoma cell lines
      but not in other cell lines. Based on this observation, we re-evaluated the
      arrangement of transcriptionally active regions in the human tenascin-R gene we
      recently cloned and found that the human gene also contains an exon sequence able
      to initiate and sustain transcription independently of promoter sequences.

PMID- 9925949
TI  - Mapping and molecular characterization of five HMG1-related DNA sequences.
AB  - Recently, the high mobility group (HMG) proteins have attracted a lot of interest
      since it was shown that some members of that group can causally be involved in
      tumorigenesis. One HMG protein gene member is HMG1 for which the number of
      related DNA sequences has been estimated to be approximately 20-30. Nevertheless,
      besides the gene for HMG1 only one retropseudogene has been molecularly
      characterized. It was the aim of this study to map and characterize further
      sequences related to HMG1. PCR-screening of a PAC library resulted in 25 very
      strongly positive clones apparently containing HMG1-like cDNA sequences. Of eight
      clones which were further investigated five were distinguishable from each other
      based on their chromosome assignment and DNA sequence. Due to their homology to
      the HMG1 gene the DNA sequences were designated as HMG1L1, HMG1L3, HMG1L4,
      HMG1L5, and HMG1L6. By FISH experiments they were assigned to 2q32, 2q35, 3p24,
      15q22, and 20q13, respectively. Except for one sequence, they did not show
      mutations leading to a frame shift or a new termination codon. Thus, we cannot
      exclude that these four HMG1-related DNA sequences represent active genes or can
      at least be activated e.g. by chromosome rearrangements in tumor cells. So far,
      the existence of six genes encoding HMG proteins has been described but because
      of a high frequency of closely related DNA sequences in the human genome it can
      be assumed that some of them are either pseudogenes or very similar genes.

PMID- 9925950
TI  - High resolution RBA-banding comparison between early prometaphase chromosomes of
      cattle (Bos taurus L.) and goat (Capra hircus L.) at 700 band level.
AB  - High resolution RBA-banded early prometaphase chromosomes of cattle (Bos taurus
      L.) and goat (Capra hircus L.), from thymidine synchronized lymphocyte cultures,
      are compared at a level of 700 bands per haploid genome, with the purpose of
      detecting the extent of banding homologies between the two species and improving
      the resolution level of the ISCNDA (1989) standardized RBA-banded karyotypes. The
      results demonstrate that, at this level of resolution, at least 10 autosomes can
      be fully homologized between the two species, namely chromosomes 11, 16, 17, 18,
      20, 21, 22, 23, 24 and 26, whereas the remaining autosomes show variations in
      some regions which require further investigations on more elongated chromosomes.
      Such investigations should also involve the use of GTG, GBG and RBG-banding
      techniques. These variations concern basically the relative distance of the bands
      from the centromeres or telomeres, appearance of subbands, and clustering of some
      positive bands.

PMID- 9925951
TI  - Characterisation and mapping of the human SOX14 gene.
AB  - SOX genes comprise a family of genes that are related to the mammalian sex
      determining gene SRY in the region that encodes the HMG-box domain responsible
      for the sequence-specific DNA-binding activity. SOX genes encode putative
      transcriptional regulators implicated in the decision of cell fates during
      development and the control of diverse developmental processes. We have cloned
      and characterised SOX14, a novel member of the human SOX gene family. Based on
      the HMG-box sequence, human SOX14 is a member of the B subfamily. SOX14 is
      expressed in human foetal brain, spinal cord and thymus, and like other members
      of the B subfamily, it might have a role in regulation of nervous system
      development. While other members of the B subfamily show similarity outside the
      HMG-box, the regions flanking the HMG box of the human SOX14 gene are unique.
      SOX14 has been mapped to human chromosome 3q22--> q23, close to the marker
      D3S1549. This location places SOX14 within a chromosome interval associated with
      two distinct syndromes that affect craniofacial development: Blepharophimosis
      ptosis-epicantus inversus syndrome and Mobius syndrome.

PMID- 9925952
TI  - Neuroimaging studies of brain activation for language, with an emphasis on
      functional magnetic resonance imaging: a review.
AB  - Neuroimaging studies have greatly enhanced the potential to understand brain
      behavior relationships in complex behaviors such as language. The method of
      functional magnetic resonance imaging (fMRI) is one of the newest tools for
      neuroimaging, and it will in all likelihood contribute substantially to new
      knowledge about brain activation for language processing. This review summarizes
      basic information about fMRI, including principles of operation, experimental
      pitfalls and examples of application to language.

PMID- 9925953
TI  - What determines the differences in perceptual rating of dysphonia between
      experienced raters?
AB  - Although the perceptual GRBAS scale for pathological voice quality has been found
      to be sufficiently reliable in clinical practice, even experienced raters
      disagree to some extent, and the degree of disagreement depends on the perceptual
      characteristics. We looked for a possible link between the degree of disagreement
      (65 voices; 2 experienced raters) and objective acoustical measurements. No
      significant correlation appeared between any acoustical parameter and the degree
      of disagreement for G. By contrast, the difference in perceptual rating of R was
      related to the amount of shimmer, and the difference in perceptual rating of B
      was related to some extent to the amount of jitter. Thus the presence of a strong
      breathy component in a pathological voice disturbs the rating of the rough
      component, and reciprocally.

PMID- 9925954
TI  - Normal swallowing physiology as viewed by videofluoroscopy and videoendoscopy.
AB  - This study examines normal oropharyngeal swallow physiology in 8 young adult
      males with concurrent videofluoroscopy and videoendoscopy. Twelve swallows were
      examined for each subject, 3 swallows each of 1 and 5 ml of thin liquid at each
      of two endoscopic positions: (1) the tip of the endoscope just at or below the
      tip of the uvula (high position), and (2) the tip of the endoscope just below the
      tip of the epiglottis (low position). Results indicate that if the clinician is
      interested in laryngeal events occurring before and after swallow, videoendoscopy
      with the endoscope in the low position is the procedure of choice. To evaluate
      pharyngeal anatomy and/or the presence of food in the pharynx before or after
      swallow, either endoscopy with the endoscope in the high position or
      videofluoroscopy can be used. However, if the clinician is interested in
      pharyngeal physiology during swallow, videofluoroscopy is a better diagnostic
      procedure.

PMID- 9925955
TI  - A comparison of babbling and speech at pre-speech level, 3, and 5 years of age in
      children with cleft lip and palate treated with delayed hard palate closure.
AB  - Babbling and speech in 21 children with cleft palate were compared at pre-speech
      level, 3, and 5 years of age. The aims were to study if misarticulations in pre
      school speech appear to be articulatorily related to the sound productions in pre
      speech, whether the feeding technique influenced the prevalence of anterior
      articulation, and if there was a relationship between speech and the size of the
      residual cleft at 3 and 5 years of age. All the children had the soft palate
      closed, whereas the cleft in the hard palate was left open to be closed later on.
      Perceptual judgement of speech revealed a high prevalence of hypernasality, nasal
      escape and retracted oral articulation of dental or alveolar plosives. The latter
      was correlated with the size of the residual cleft area. There was a tendency
      towards a relationship between absence of anterior sound productions in babbling
      and retracted oral articulation in speech. The feeding technique, however,
      appeared not to have had any influence on articulatory place.

PMID- 9925956
TI  - In situ localization of pollen allergens by immunogold electron microscopy:
      allergens at unexpected sites.
AB  - The windborne pollen grains of many trees and grasses contain a number of highly
      water-soluble (glyco)proteins which upon moistening, e.g. on the human
      respiratory mucosa, rapidly diffuse out of the pollen grain. In susceptible
      individuals, they may cause allergic reactions. Because of their rapid release
      from the pollen, pollen allergens were expected to be located in the outermost
      layers of the pollen grain, i.e. on the surface and in the wall (exine, intine).
      First attempts to localize allergens by microscopic methods in the pollen grain
      supported this view. However, since conventional preparation methods were used,
      artificial mobilization of allergens could not be excluded. Based on new,
      completely anhydrous preparation protocols and on the immunogold-labeling
      technique, pollen allergens were electron-microscopically shown to be located in
      the interior of the pollen grain, i.e. in the cytoplasm, often within ribosome
      rich areas. This unexpected result was obtained in all strictly anhydrously
      prepared pollen species. The biological function of these allergens is largely
      unknown, however, clues as to possible cellular functions have been obtained for
      the birch pollen major allergen Bet v 1.

PMID- 9925957
TI  - Regulation of eosinophil apoptosis: transduction of survival and death signals.
AB  - Since eosinophils are prominent in allergic inflammation, investigators became
      interested in how these cells accumulate in tissues and their role within the
      inflammatory cascade. There is increasing evidence from several laboratories that
      eosinophil numbers are regulated in vivo, not only by eosinophil production in
      the bone marrow, but also by the amount of eosinophil apoptosis. Moreover, it has
      been directly demonstrated that eosinophil apoptosis is delayed in allergic
      inflammatory sites, and that this mechanism contributes to the expansion of these
      cells in tissue. In this article, we review recent studies that shed light on the
      intracellular pathways that control eosinophil apoptosis.

PMID- 9925958
TI  - Molecular analysis of the group 1 and 2 allergens from the house dust mite,
      Euroglyphus maynei.
AB  - BACKGROUND: There is increasing evidence that the house dust mite Euroglyphus
      maynei may be a significant source of allergic sensitization. The structural
      information for the E. maynei allergens is largely restricted to a single partial
      genomic sequence of Eur m 1. METHODS: A cDNA library was constructed from a
      culture of E. maynei. Clones encoding the major group 1 and 2 allergens were
      isolated by DNA hybridization and sequenced. RESULTS: The sequence of several
      full length clones of Eur m 1 and Eur m 2 were obtained. The full pre-proenzyme
      sequence of the cysteine protease Eur m 1 was determined. The translated amino
      acid sequence of Eur m 1 and Eur m 2 had 84-86% sequence identity with the
      corresponding allergens from Dermatophagoides pteronyssinus and Dermatophagoides
      farinae mites. This is the same as the degree of sequence identity found between
      D. pteronyssinus and D. farinae despite Euroglyphus being a member of the
      Pyroglyphinae subfamily rather than the Dermatophagoidinae subfamily. CONCLUSION:
      The sequences of the major Eur m 1 and Eur m 2 allergens are described. Their
      degree of divergence from the Dermatophagoides spp. is similar to that observed
      between D. pteronyssinus and D. farinae group 1 and group 2 allergens.

PMID- 9925959
TI  - Immune response and airway reactivity in wild and IL-4 knockout mice exposed to
      latex allergens.
AB  - BACKGROUND: Natural rubber latex has been reported as a major cause of allergy
      and asthma in a number of individuals. One of the occupational groups most
      affected by latex allergy are the health care workers who are frequently exposed
      to natural rubber latex products in their patient care activities. The
      immunopathogenesis of latex allergy is not well understood. In order to
      understand the immune mechanism in latex allergy, we have developed a mouse model
      of latex allergy. METHODS: Both wild-type and IL-4 knockout BALB/c mice were
      challenged intranasally with latex proteins and their immune responses, lung
      pathology, and airway reactivity were evaluated. RESULTS: The total serum IgE and
      latex specific IgE, IgG1, and peripheral blood and lung eosinophil levels in wild
      type BALB/c mice were enhanced by the latex exposure, while no IgE or eosinophil
      were detected in IL-4 knockout mice. Latex-specific IgG1 levels in the sera were
      lower in IL-4 knockout animals compared to wild mice. However, latex-specific
      IgG2a antibody was higher in all the IL-4 knockout mice compared to wild type
      mice. Both the wild type and IL-4 knockout animals developed increased airway
      resistance after antigen challenge when compared to control animals, although the
      airway resistance response of IL-4 knockout animals was attenuated compared to
      the wild-type animals. The histology of the lungs of these two groups of animals
      was similar. CONCLUSION: In spite of the differences in the immune responses in
      the two groups of mice, there were comparable lung inflammatory responses,
      suggesting a multifactorial pathogenetic mechanism.

PMID- 9925960
TI  - Protein tyrosine phosphorylation: A possible common signaling pathway in human
      Th1 and Th2 cell clones.
AB  - BACKGROUND: It has been reported that protein tyrosine phosphorylation is
      essential for cytokine production in mouse Th1 cells but not in Th2 cells.
      However, little is known about the difference of signal transduction between
      human antigen-specific Th1 and Th2 cell clones. METHODS: Purified protein
      derivative-specific Th1 and Dermatophagoides farinae-specific Th2 cell clones
      were established. T cell clones were stimulated with anti-CD3 Abs and further
      treated with goat antimouse immunoglobulin Abs for cross-linking of TCR/CD3
      complex. RESULTS: In contrast to murine Th2 clones, tyrosine phosphorylation
      including both ZAP-70 and phospholipase-C-Al was necessary for cell activation in
      both types of human T cell clones. This was further supported by the observation
      that genistein (protein tyrosine kinase inhibitor) inhibits IFN-A production for
      Th1 and IL-4 for Th2 in a dose-dependent manner. CONCLUSION: Protein tyrosine
      phosphorylation is thus an essential component in transducing the activation
      signal from TCR-CD3 complex both in human Th1 and Th2 cells.

PMID- 9925961
TI  - Role of CD4-positive T cells in the pathogenesis of nasal allergy in the murine
      model.
AB  - BACKGROUND: Antigen-induced upregulation of cytokines, especially Th2-type
      cytokines, has been proven to be closely related to allergic inflammation in
      nasal allergy. CD4-positive T cells are supposed to play an important role not
      only in the induction of allergy but also in allergic inflammation. METHODS: The
      anti-CD4 mAb was administered to the murine model of nasal allergy either at the
      beginning of sensitization, just before antigen challenge or during a topical
      booster sensitization. Then, the effects on the antigen-induced nasal responses
      and the serum level of antigen-specific IgE antibody were evaluated. RESULTS:
      When the mAb was applied at the beginning of sensitization, the early-phase nasal
      symptoms and the late-phase nasal eosinophilia were significantly inhibited, and
      the 8-day passive cutaneous anaphylaxis (PCA) titer tended to be inhibited. When
      the mAb was applied just before the challenge, there were no differences in the
      nasal symptoms, the nasal eosinophilia or the 8-day PCA titer between the mAb
      treated animals and the control animals. When the mAb was applied during a
      topical booster sensitization, the nasal eosinophilia, the 8-day PCA titer and
      histamine hypersensitivity were significantly suppressed in the treated animals.
      CONCLUSION: CD4-positive T cells play an important role in the induction of IgE
      mediated nasal allergy, occurrence of late-phase allergic inflammation and
      histamine hypersensitivity, but not in antigen-induced early-phase nasal symptoms
      in the murine model. In cases of chronic topical antigen exposure, however, the
      suppressive effects of a single application of the anti-CD4 mAb are not
      remarkable.

PMID- 9925962
TI  - Effect of interleukin-3, interleukin 5 and hyaluronic acid on cultured
      eosinophils derived from human umbilical cord blood mononuclear cells.
AB  - BACKGROUND: Several studies have shown that cultured eosinophils can be generated
      from human umbilical cord blood mononuclear cells (UCMC) in the presence of
      interleukin (IL)-3 and IL-5 in vitro. Other reports have indicated that cellular
      adhesion to hyaluronic acid (HA) enhances the proliferation of cultured
      eosinophils derived from CD34+ cells purified from UCMC. The aim of this study
      was to obtain large numbers of mature eosinophils from UCMC using IL-3, IL-5 and
      HA, and to investigate their functions. METHODS: We examined several combinations
      of IL-3 and IL-5 and their effect on eosinophil development from UCMC in HA
      coated on non-coated flasks. We also examined whether cultured eosinophils
      degranulated eosinophil-derived neurotoxin (EDN) induced by secretory
      immunoglobulin A conjugated to sepharose beads (sIgA-beads) and responded to
      eotaxin. RESULTS: Culture with HA-coated flasks for 35 days (in the presence of
      IL-3 and IL-5, with IL-3 omitted after day 14 of culture) caused a 11.2-fold
      augmentation in the proliferation of UCMC. On day 35 of the culture, 98% of
      cultured cells were eosinophils judging from May-Grunwald and Giemsa staining and
      transmission electron micrographs. The EDN content of the cultured eosinophils on
      day 35 was 156 ng/105 cells. Cultured eosinophils degranulated EDN induced by
      sIgA-beads and responded to eotaxin by chemotaxis and intracellular Ca2+
      mobilization. CONCLUSION: We found a useful culture system to obtain large
      numbers of eosinophils derived from UCMC, which may facilitate the investigation
      of eosinophil function, since there was no significant difference in response to
      sIgA-beads and eotaxin between cultured and peripheral eosinophils.

PMID- 9925963
TI  - 111In-labelled leukocyte migration to the lungs of ovalbumin-sensitized guinea
      pigs after aerosol challenge with ovalbumin monitored by gamma scintigraphy.
AB  - BACKGROUND: To determine whether antigen challenge is associated with increased
      accumulation of leukocytes in the lungs, the pulmonary accumulation of 111In
      labelled neutrophils and eosinophils was monitored by gamma scintigraphy.
      METHODS: Guinea-pigs were sensitized with ovalbumin (OA) 14-21 days before
      challenge with aerosolized OA (10 mg/ml) for 2 min, and protected against fatal
      anaphylaxis by mepyramine (30 mg/kg). Comparisons were made with OA-sensitized
      guinea-pigs challenged with saline. 5 or 24 h following the OA challenge, guinea
      pigs were anaesthetized and the jugular vein and right carotid artery were
      cannulated, with the contralateral artery tied off. 2MBq 99mTc macroaggregated
      albumin (MAA) was injected intravenously to create a pulmonary perfusion image as
      a template for the lungs. 111In-labelled neutrophils or eosinophils were then
      injected via the carotid artery and gamma scintigraphic images obtained. Activity
      in the lung region of each animal was determined by superimposing the 99mTcMAA
      image of the lungs on the whole body image. RESULTS: A significant increase in
      activity (p<0.05) in the lung region was observed after injection of 111In
      labelled neutrophils at 5 h after the OA challenge compared with saline
      challenge. 24 h after OA challenge there was a significant increase in activity
      (p<0.05) in the lung region after injection of 111In-labelled eosinophils, but no
      change in activity after injection of labelled neutrophils compared with the
      saline-challenged animals. CONCLUSION: This technique models the migration of
      leukocyte to the lungs seen in guinea-pigs in our previous studies, namely an
      eosinophilia at 24 h and a neutrophilia at 5 h after OA challenge. It will
      therefore be useful for investigating anti-inflammatory drugs on the airways.

PMID- 9925964
TI  - Monoclonal IgG antibodies influence the migration patterns of lymphocytes in
      vivo.
AB  - Monoclonal antibodies (MoAb) are useful therapeutic agents for the treatment of a
      variety of human disorders, although the effector mechanisms responsible for the
      outcome of an efficient immunotherapy remain unclear. This study was designed to
      address the early effects of MoAb on the migration patterns of lymphocytes in
      vivo. The clearance profiles and tissue distribution of 111In-labelled rat lymph
      node cells were examined in both normal and decomplemented allogeneic and semi
      allogeneic recipients pre-injected with IgG2b (R3/13) or IgG2a (R2/15S) MoAb
      directed against the RT1Aa, the classical class I major histocompatibility
      complex antigen of the DA rat. Both MoAb were equally effective in not only
      augmenting the removal of DA and (DA x PVG)F1 cells from the circulation and
      promoting their subsequent localization within the liver but also causing a
      significant degree of cell lysis during the early phase of cell clearance, even
      in decomplemented recipients. Although R3/13 and R2/15S are known to target
      erythrocytes differently in normal and cobra venom factor (CVF)-treated animals,
      no differences were observed in the migration behaviour of lymph node cells in
      allogeneic or semi-allogeneic hosts pre-injected with the same MoAb. Since rat
      lymphocytes express a much higher level of the RT1Aa antigen as compared with
      erythrocytes, we could not exclude a possible role of residual complement
      components in the circulation of CVF-treated rats that may have accounted for the
      observed antibody-dependent effects on target lymphocytes. On the basis of these
      findings we believe that the design and methodology employed in our present
      experimental opsonization system were inadequate to define clearly the mechanisms
      responsible for antibody-mediated removal and destruction of target lymphocytes
      in vivo.

PMID- 9925965
TI  - Lack of systemic anaphylaxis and aeroallergen-induced airway plasma extravasation
      in allergic immunoglobulin-deficient mice.
AB  - BACKGROUND: In Ig-deficient mice allergen challenge-induced pulmonary late phase
      inflammation is at least as pronounced as in wild-type animals. This study
      investigates immediate hypersensitivity responses in these mice. METHODS: To
      examine the acute plasma extravasation response in airway tissue, immunized Ig
      deficient and wild-type mice and sham-immunized wild-type controls were subjected
      to 15 min ovalbumin aerosol challenge. 125I-albumin was injected (i.v.) 1 min
      prior to challenge. Immediately after challenge 131I-albumin was injected and the
      experiment was terminated. Plasma and trachea were analyzed for 125I and 131I,
      and the amount of extravasated plasma in the trachea was calculated. To study the
      development of systemic anaphylaxis immunized Ig-deficient and wild-type animals
      received intravenous allergen challenge followed by determination of mast cell
      responses and plasma histamine levels. RESULTS: Allergen aerosol-exposed
      immunized wild-type mice exhibited marked plasma extravasation in the trachea
      (pd0.01 vs. wild-type controls), but in the corresponding Ig-deficient mice there
      was no increased extravasation. Immunized Ig-deficient mice receiving intravenous
      allergen challenge were resistant to anaphylactic shock. By contrast, the wild
      type animals developed systemic anaphylaxis, accompanied by plasma extravasation,
      mast cell degranulation, elevated plasma histamine and rapid death. CONCLUSION:
      The present data are evidence that immunoglobulins are crucial for the
      development of immediate (type 1) responses. These findings together with our
      previous observations on late-phase pulmonary responses suggest that immediate
      hypersensitivity processes are unimportant for development of the late phase
      inflammation in the respiratory tract of mice.

PMID- 9925966
TI  - Atypical CD3+ CD4(low) cell population in a boy with fatal EBV-infection.
AB  - A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy
      parents developed progressive liver disease after acute infectious mononucleosis.
      EBV-induced autoimmune hepatitis was suspected and treatment was started with
      high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite
      therapy, his liver function continuously deteriorated and the child died 9 months
      later in profound immune deficiency from candida septicemia. Flow cytometric
      analysis of his lymphocytes revealed a major subpopulation of atypical cells
      (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low
      level of CD4 expression, comparable to that of monocytes. After short-time cell
      culture, the cells became adherent and developed granules and dendrites. We
      conclude that these cells may represent strongly activated CD4+ T lymphocytes
      with downregulated CD4 expression or a subtype of dendritic cells.

PMID- 9925967
TI  - Correlation of EGTA and calcium-blocking agents on the response of the bladder to
      in vitro ischemia.
AB  - The effects of repetitive field stimulation (model of hyperrelexia) on the
      responses of isolated strips of rabbit urinary bladder to FS and carbachol were
      evaluated under a variety of incubation conditions. Compared to control
      conditions, 2 h of repetitive FS in normal, oxygenated Tyrode's solution followed
      by incubation for 1 h with no stimulation resulted in a 50% decrease in
      contractile response to FS and a 30% decrease in the response to carbachol.
      Incubation in the absence of O2 and glucose was used as an in vitro model for
      ischemia. Repetitive stimulation during in vitro ischemia resulted in a
      significantly greater decrease in the contractile responses to FS and carbachol
      than did in vitro ischemia without repetitive stimulation. The magnitude of
      contractile dysfunctions in response to both stimuli were significantly reduced
      in the presence of EGTA (calcium chelator), diltiazem (calcium channel blocker)
      or pincidil (potassium channel opener). Incubation with thapsigargin (SR calcium
      uptake inhibitor) + ryanodine (SR calcium storage inhibitor) had no effect. The
      results of these studies indicate that inhibition of Ca2+ entry reduces the
      contractile dysfunctions induced by repetitive stimulation in the presence of in
      vitro ischemia. Inhibition of Ca2+i storage and release had no significant effect
      on the magnitude of contractile dysfunctions induced by repetitive stimulation an
      in vitro ischemia.

PMID- 9925968
TI  - N-Acetylheparin pretreatment reduces infarct size in the rabbit.
AB  - The ability of the heparin derivative, N-acetylheparin (NHEP) to protect the
      heart from regional ischemia/reperfusion injury was examined in vivo. NHEP (2
      mg/kg i.v.) or vehicle was administered 2 h before occlusion of the left
      circumflex coronary (LCX) artery. Open-chest, anesthetized rabbits were subjected
      to 30 min of regional myocardial ischemia followed by 5 h of reperfusion.
      Myocardial myeloperoxidase activity, membrane attack complex (MAC) deposition and
      IL-8 generation were assessed in supernatant samples from the area at risk.
      Infarct size in rabbits pretreated with NHEP (32.5 +/- 3.8%, n = 10) decreased by
      41% compared to infarct size in rabbits that received vehicle (55.3 +/- 4.9%, n =
      10; p = 0.002). Accumulation of neutrophils within the ischemic region, as
      assessed by myeloperoxidase activity, declined by 45% (p < 0.05) in AAR from NHEP
      treated animals compared to AAR from vehicle-treated animals. Levels of MAC and
      IL-8 obtained from AAR were less in NHEP-pretreated animals compared to controls.
      These results suggest that NHEP may protect the myocardium by inhibiting
      complement activation and subsequent neutrophil infiltration.

PMID- 9925969
TI  - Effects of losartan on the sexual behavior of male rats.
AB  - Many commonly used antihypertensive drugs such as diuretics and beta-blockers can
      interfere with sexual function in both sexes, causing loss of libido, impairment
      of erectile function and ejaculation in men, and delay or prevent orgasm in
      women. Newly developed antihypertensive drugs should ideally not interfere with
      the patients' quality of life including sexual function. This study examined the
      effects of losartan, a nonpeptide, specific antagonist for type I angiotensin II
      receptors, on the male sexual behavior of rats. Spontaneously hypertensive rats
      (SHRs) and normotensive Wistar-Kyoto (WKY) rats were treated with losartan 30 mg/
      kg/day or saline control for 7, 30 and 90 days. Dark-cycle video recording was
      used to analyze the male sexual activities of the rats. No significant alteration
      in male sexual performance was observed after 7 and 30 days of treatment with
      losartan. In contrast, SHRs treated with propranolol 5 mg/kg/day showed increases
      in intromission latency, ejaculation latency and postejaculatory period
      indicating decreased libido and erectile and ejaculatory function. Upon
      completion of 90 days of losartan administration, the mount latency of the SHR
      was significantly increased, suggesting a decrease in libido although other
      parameters were unchanged and there was no effect in WKY rats. It is therefore
      concluded that losartan may have an advantage in preservation of sexual function
      when used clinically for the treatment of hypertensive disorders.

PMID- 9925970
TI  - Studies on pyrazinoylguanidine. 7. Effects of single oral doses in normal human
      subjects.
AB  - In a three-phase study, single oral doses of placebo, followed in 1 week by
      pyrazinoylguanidine (PZG; 900 mg), followed in 3 weeks by pyrazinoic acid (PZA;
      300 mg) were given to 8 normal male subjects. Blood analyses performed 0, 2 and 4
      h after administration of placebo or drug revealed that compared to mean 0 h
      values, PZG and also PZA, but not placebo, decreased mean values for serum
      glucose, insulin, C-peptide, triglycerides and free fatty acids. In all groups,
      serum potassium, urea, fibrinogen, high-density lipoprotein and low-density
      lipoprotein were unchanged. PZA, but not PZG, increased serum uric acid. PZG
      significantly reduced very-low-density lipoprotein whereas PZA only tended to do
      so. PZG was well tolerated and without any side effect, but in 7 of the 8 normal
      volunteers, PZA produced a variable vasomotor response over the blush area of the
      face and neck lasting from 30 min in 3 subjects to 4 h in 1 subject.
      Collectively, these results suggest generally similar metabolic responses of
      normal subjects to PZG and PZA after only a single oral dose of each. Previously,
      it was unrecognized that acute administration of PZG and PZA could produce such
      rapid metabolic changes.

PMID- 9925971
TI  - In vitro biotransformation of a novel antimalarial cysteine protease inhibitor in
      human liver microsomes.
AB  - 4-Dimethylamino-4'-(imidazol-1-yl)chalcone (RL3142) is a newly developed
      antimalarial cysteine protease inhibitor. Four metabolites (M1-M4) were found in
      human liver microsomes and their structures were identified by LC/MS/MS. Two
      primary metabolites, M2 (minor) and M4 (major), were determined to be the N
      demethylated product (M2) and the product (M4) resulting from 1,2-hydrogenation
      of the alpha, beta-unsaturated ketone moiety of the parent compound. A combined
      approach utilizing selective P450 inhibitors, immunoinhibition with CYP3A and
      NADPH P450 reductase antibodies, and cDNA expressed human CYP3A4 and NADPH P450
      reductase, was used for identification of enzymes responsible for the
      biotransformation. For formation of M2, both a rabbit CYP3A polyclonal antibody
      (110 microliter/mg microsomal protein) and ketoconazole (2 micromol/l), a CYP3A
      inhibitor, showed about 50% inhibitory effects; other specific inhibitors of
      CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 showed no significant effects.
      For formation of M4, neither CYP3A antibody nor the above mentioned CYP
      inhibitors exhibited inhibitory effects. Anti-rat NADPH P450 reductase serum (50
      microliter/100 microgram microsomal protein) exhibited 70 and 58% inhibitory
      effects on M2 and M4 formation, respectively. Incubation of RL3142 with cDNA
      expressed human NADPH P450 reductase yielded formation of M4, but not M2. Carbon
      monoxide inhibited formation of M2 and M1 (the reduced product of M2), but had no
      effect on M4 and M3 (the reduced product of M4) formation. Collectively, NADPH
      P450 reductase solely catalyzed reduction of RL3142 to M4, whereas CYP3A
      contributed in part to formation of M2.

PMID- 9925972
TI  - Inhibition of calcium influx during hypoxia/reoxygenation in primary cultured rat
      hepatocytes.
AB  - Calcium has been demonstrated to play an important role in hepatocyte damage
      during ischemia/reperfusion phases. Calcium influx was determined in primary
      cultured rat hepatocytes submitted to a succession of warm hypoxia and
      reoxygenation phases in the presence of diltiazem, gallopamil and a Na+/H+
      antiport inhibitor, HOE-694. Only diltiazem significantly inhibited calcium
      influx with higher potency after reoxygenation than after hypoxia only,
      suggesting a complex mechanism of action of diltiazem which could act on
      different physiological functions involved in Ca2+ invasion of hepatocytes after
      hypoxic insult.

PMID- 9925973
TI  - The effectiveness of parents in promoting the development of road crossing skills
      in young children.
AB  - BACKGROUND: Young children show poor judgment when asked to select a safe place
      to cross the road, frequently considering dangerous sites to be safe.
      Correspondingly, child pedestrian accidents are over-represented at such
      locations. Increasing the child's ability to recognise such dangers is a central
      challenge for road safety education. AIMS: Practical training methods have proved
      effective in improving such judgments but are labour-intensive, time-consuming
      and therefore difficult to implement on a realistic scale. The study examined the
      possibility that volunteers from the local community might be capable of using
      such methods to promote children's pedestrian competence. SAMPLE: Sixty children
      from the Primary 1 (Reception) classes of three Glasgow schools took part.
      Volunteers were ordinary parents from the same areas. None had 'formal'
      experience of working with children other than through being parents. METHOD:
      Volunteers received experience of training children at courses organised in each
      school. Children learned in small groups, receiving two sessions of roadside
      training followed by four on a table-top model. Pre- and post-tests allowed the
      effectiveness of training to be assessed. RESULTS: Significant improvements
      relative to controls were found in all children following training. Improvements
      proved robust and no deterioration was observed two months after the programme
      ended. Comparison with a previous study in which training was undertaken by
      highly qualified staff showed that the volunteers were as effective as 'expert'
      trainers. CONCLUSIONS: Parent volunteers can significantly increase the
      pedestrian competence of children as young as five years. They constitute a most
      valuable 'resource' in road safety education. The opportunities afforded by
      involving the local community in educational interventions should be further
      explored.

PMID- 9925974
TI  - An intervention programme for children with moderate learning difficulties.
AB  - BACKGROUND: Children with learning difficulties typically demonstrate problems
      generalising what they have learned in specific contexts to new situations.
      Intervention programmes that teach children regulatory skills have been shown to
      overcome these problems for children with reading difficulties. This study
      applies the principles that underlie such interventions to the design of a
      programme for children with more general learning difficulties. AIM: The aim of
      the study reported here was to design and evaluate an intervention programme
      which would facilitate the transfer of skills learned over the course of the
      intervention to different types of task. SAMPLE: A total of 41 children (aged 13
      16 yrs; 14 females, 27 males) with moderate learning difficulties participated in
      the intervention programme. METHOD: The children participated in a twelve-week
      intervention programme designed to promote regulatory strategies over a range of
      activities. The children worked in pairs and were guided by an adult who provided
      explicit instruction and modelled appropriate strategies. The children were
      assessed before and after the programme to determine whether improvements in
      strategic behaviour were evident and whether this generalised to new situations.
      RESULTS: Gains made in regulatory skills over the course of the intervention were
      accompanied by improvements in other performance measures such as reading and IQ.
      CONCLUSIONS: Even after a relatively short intervention, which focused on the
      development of regulatory skills, significant improvements on a range of tasks
      were observed for a group of children with moderate learning difficulties.

PMID- 9925975
TI  - Self-reports of mathematics self-concept and educational outcomes: the roles of
      ego-dimensions and self-consciousness.
AB  - BACKGROUND: There is a need for research to (a) explore more fully the academic
      outcomes that follow from under-/over-rating of self-concept and (b) identify
      factors that predict the nature of self-reports of self-concept as well as under-
      and over-rating of this self-concept. AIMS: The study examines the link between
      students' self-appraisals of both mathematics self-concept and under-/over-rating
      of this self-concept and educational outcomes in mathematics such as achievement
      and motivation (future plans for mathematics). Ego-dimensions (ego-orientation
      and competence-valuation) and public self-consciousness were examined as two
      factors that might contribute to predicting these self-appraisals. SAMPLE:
      Findings are drawn from a sample of 382 male and female high school students
      ranging in age from 14 to 16 years. METHODS: Students responded to a
      questionnaire (at Time 1) that assessed self-concept, motivation orientation,
      competence-valuation, self-consciousness, and mathematics motivation. Teachers
      rated each student using a brief mathematics self-concept scale. RESULTS: Higher
      mathematics self-concept and over-rating of this self-concept were predictive of
      higher levels of mathematics motivation and later mathematics achievement (Time
      2). Findings also indicate that ego-orientation and competence-valuation are
      positively associated with mathematics self-concept and over-rating, whilst
      public self-consciousness negatively predicts mathematics self-concept and is
      also associated with a tendency to under-rate oneself in this domain.

PMID- 9925977
TI  - Super-aspirins in severe angina.

PMID- 9925976
TI  - Attributional style and its relation to other personality dispositions.
AB  - BACKGROUND: People vary greatly with respect to the way they explain negative
      events (personal failures), and this variation in attributional style seems to be
      related to various personality traits and also academic performance. For example,
      the theory of learned helplessness regards a pessimistic attributional style as
      an important determinant in the development of depression. AIM: The primary
      purpose of the present study was to compare attributions for positive and
      negative events with respect to correlations with seven personality dispositions.
      The comparisons concern the three attributional dimensions internality, stability
      and globality, as well as their combination. The hypothesis was that attributions
      for positive events are differently correlated with the seven personality
      dispositions than are attributions for negative events. SAMPLE: 166 advanced
      teacher students (132 females and 34 males). METHOD: On the basis of an inventory
      the students were given scores on the attributional variables (related to
      imagined positive and negative academic events), global and academic self-esteem,
      motive to seek success, motive to avoid failure, self-efficacy, defensiveness,
      and depression. RESULTS: The hypothesis was confirmed. Attributions for positive
      events correlated differently with the seven personality dispositions than
      attributions for negative events. Also, factor analysis of the attributional
      dimensions indicated that attributions for positive events measured quite
      different components than attributions for positive events. CONCLUSION: The
      general conclusion is that both event kinds should be considered when using
      attributional style for predicting or explaining personality and behavioural
      variables.

PMID- 9925978
TI  - Are all statins equal?

PMID- 9925979
TI  - Studies confirm link between fen-phen and heart-valve disease.

PMID- 9925980
TI  - New interactive Web site on cholesterol reduction.

PMID- 9925981
TI  - Inflammatory marker predicts heart-attack risk for healthy women.

PMID- 9925982
TI  - Evidence for benefit from beta blockers in congestive heart failure.

PMID- 9925983
TI  - My home blood-pressure monitor always gives me readings in the normal range, but
      when I go to my doctor, the readings are 160/90, or higher. I think I have white
      coat hypertension, but how can I be sure?

PMID- 9925984
TI  - I have atrial fibrillation and take a blood thinner to help prevent strokes. My
      problem is that my energy level has been so low since I developed this problem
      that I cannot do basic things like shopping and housework. My doctor cannot find
      any other problem that might account for my fatigue.

PMID- 9925985
TI  - Evidence-based medicine on the wards: report from an evidence-based minion.

PMID- 9925986
TI  - Transcriptional regulation and biological significance of the insulin like growth
      factor II gene.
AB  - The insulin like growth factors I and II are the most ubiquitous in the mammalian
      embryo. Moreover they play a pivotal role in the development and growth of
      tumours. The bioavailability of these growth factors is regulated on a
      transcriptional as well as on a posttranslational level. The expression of non
      signalling receptors as well as binding proteins does further tune the local
      concentration of IGFs. This paper aims at reviewing how the transcription of the
      IGF genes is regulated. The biological significance of these control mechanisms
      will be discussed.

PMID- 9925988
TI  - Dependence of timing of mitotic events on the rate of protein synthesis and DNA
      replication in sea urchin early cleavages.
AB  - To understand what processes affect the cell-cycle timing of mitotic events in
      early cleavage cycles of sea urchin embryos, a study was made on the effects of
      (a) reducing protein synthesis with emetine and (b) DNA replication with
      aphidicolin, on the timing of nuclear envelope breakdown, anaphase onset and
      cytokinesis. When protein synthesis was slightly inhibited by administration of
      emetine, the delay in the mitotic events increased, with an increase in the delay
      in accumulation of proteins up to the levels to which cells must synthesize the
      proteins to execute the cleavage. This indicated that protein synthesis affects
      the timing of mitotic events. The delay in cleavage cycles caused by a slight
      inhibition of DNA replication with aphidicolin was in proportion to the
      concentration of aphidicolin administered, suggesting that DNA replication also
      affects the timing of mitotic events. Furthermore, it was confirmed that
      accumulation of the proteins to the levels required for execution of the first
      cleavage precedes completion of DNA replication as a requirement for execution of
      the first cleavage. These results imply the existence of process(es) affected by
      protein synthesis that are included in a feedback control system which prevents
      the initiation of mitosis until after the completion of DNA replication; it is
      the characteristic of a cell-cycle control system that has been predicted
      theoretically.

PMID- 9925987
TI  - Temporal variation in cellular proliferation during recornification of mouse tail
      skin.
AB  - The influence of the time of injury on subsequent epidermal regeneration is
      unknown. Epidermal cell proliferation of tail skin in C57BL/6J mice in response
      to tape stripping was followed for 7 days by radiolabelled thymidine
      incorporation and autoradiography. The homeostatic labelling index (LI) of the
      basal epidermis of unmanipulated, unwounded (control) animals was 7.6% and did
      not vary depending on the time of day. Tape stripping increased the LI of
      epidermal basal cells 110% above control values 24 h after injury. Labelling
      indexes of epidermal basal cells in the skin adjacent to the wounded area were
      7.0%. Basal cell DNA synthesis stimulated by wounding exhibited a distinct
      temporal variation at 24 h postinjury, with tail skin wounded at 12.00 h found to
      be 275% greater than control values and elevated 78% from LIs recorded at any
      other time point. This temporal spike was due to the time of day at which
      wounding occurred rather than the time point when the LI was determined. Mice
      wounded at 12.00 h and terminated 27 h later (15.00 h) had LIs that were 52%
      greater than wounds created at 09.00 h and examined at 12.00 h the following day.
      Higher levels of DNA synthesis in tail skin injured at 12.00 h compared to
      wounding at 09.00 h was detected 12-48 h after injury. Furthermore, DNA synthesis
      in wounds created at 12.00 h returned to baseline levels 1-2 days earlier than
      tail skin wounded at 09.00 h. Investigation of other strains of mice detected
      differences in radiolabelling of epidermal basal cells 24 h after tape stripping
      at 12.00 h or 09.00 h in CD-1 and BALB/cJ mice, but not in the C3H/HeJ strain.
      These results indicate: (a) there is no diurnal variation in the LI of mouse tail
      skin under normal homeostatic conditions (b) tape stripping is a potent
      stimulator of basal cell turnover in the epidermis (c) the time of wounding
      determines the magnitude of the increase in the LI of basal cells following
      injury, and (d) the proliferative response to wounding of the tail is dependent
      on the strain of mouse.

PMID- 9925990
TI  - Coronary thrombosis. Effects of blood flow on the mechanism of thrombus
      formation.
AB  - The mechanism of arterial thrombosis, including coronary thrombosis, is different
      from that of thrombosis which occurs at sites of blood stasis such as deep venous
      thrombosis. Considering the onset of arterial thrombus formation, soluble
      coagulant factors may not play important roles for its onset since they are
      diluted by the effect of blood flow and cannot reach high enough concentrations
      to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen
      even in the presence of shearing effects of blood flow, may play a crucial role
      in the onset of arterial thrombus formation. Thus, the mechanism of platelet
      thrombus formation should be assessed in the presence of blood flow. However,
      current dogma that fibrinogen binding to activated GP IIb/IIIa is the final
      common pathway for platelet thrombus formation was developed by using the
      function assay system of aggregometer, in which the effects of blood flow were
      not seriously considered. We are proposing in this review that plasma ligand
      protein of von Willebrand factor (vWF) and its interactions with platelet GP lb
      and GP IIb/IIa, which become apparent only in assays systems under influence of
      high shear rates of flow condition such as flowchambers or coneplate viscometers,
      are the key events leading to the onset of arterial thrombosis. A better
      understanding of the vWF-mediated mechanism of platelet thrombus formation is
      important for the development of better clinical tools to prevent ischemic heart
      disease as well as for a complete understanding of the mechanism of coronary
      thrombosis.

PMID- 9925991
TI  - Usefulness of exercise thallium-201 imaging in evaluation of low- and high-risk
      groups in coronary artery disease patients with disappearance of anginal episodes
      by anti-anginal drug therapy.
AB  - Our objective was to clarify the management of patients with silent myocardial
      ischemia (SMI) and documented coronary artery disease. We evaluated 222 such
      patients who did not develop anginal pain during exercise thallium-201 imaging
      (ST-TL). They were divided into low- and high-risk groups based on results of
      left ventriculographic findings at rest, ST-TL, and coronary angiography. The
      incidence of cardiac events was 28/222 (13%) overall, being 9 of 110 (8%) in the
      low-risk patients, and 19 of 112 (17%) in the high-risk group. Kaplan-Meier
      survival analysis revealed a significant difference between the two groups (p =
      0.020). Analysis of the survival of the high-risk group revealed significant
      differences between the patients with a negative and positive redistribution (p =
      0.047), but such differences were not significant in the low-risk patients.
      Therefore, the classification of SMI patients into low- and high-risk categories
      was an appropriate strategy. ST-TL was useful for identifying patients with
      myocardial ischemia and selecting those to receive coronary revascularization
      and/or drug therapy.

PMID- 9925989
TI  - Effects of thiols on topoisomerase-II alpha activity and cell cycle progression.
AB  - Thiol containing compounds exhibiting antioxidant properties are currently being
      evaluated for use in cytoprotection and chemoprevention. Many of these have also
      been found to be effective in inhibiting cell cycle progression and cellular
      proliferation. N-Acetyl-L-cysteine (L-NAC), along with its nonmetabolically
      active stereoisomer N-acetyl-D-cysteine (D-NAC), together with captopril and
      dithiothreitol (DTT) were investigated to assess their effects on cell cycle
      progression as determined by flow cytometry. Topoisomerase-IIa (topo-II alpha)
      activity, an enzyme involved in DNA synthesis, was also monitored as a function
      of drug dose using a kinetoplast DNA (kDNA) decatenation assay. Chinese hamster
      ovary (CHO) AA8 cells were exposed to each thiol at concentrations ranging from 4
      microM to 4 mM for a period of 3 h. Following the removal of the thiols, cell
      cultures were followed for an additional 5 h to assess changes in cell cycle
      progression. L-NAC, which also serves as a precursor for glutathione (GSH)
      synthesis, effectively inhibited topo-IIa activity by at least 50% at all
      concentrations tested. Associated with this reduction in enzyme activity was a
      sixfold increase in the relative number of cells accumulating in G2phase. D-NAC,
      which is unable to participate in GSH synthesis, was only half as effective as L
      NAC at each concentration tested in inhibiting topo-IIa activity as well as
      perturbing cell progression through G2. In comparison, captopril, an inhibitor of
      angiotensin converting enzyme (ACE), had little effect on the progression of
      cells into G2 phase. In contrast to the repressive effects of L-NAC and D-NAC, it
      enhanced topo-IIa activity over control values by approximately 20%. DTT, a well
      characterized thiol known to be capable of reducing disulphides in proteins, was
      observed to be relatively ineffective in either perturbing cell cycle progression
      or affecting topo-IIa activity. This suggests an involvement of a mechanism(s) in
      addition to thiol mediated affects on reduction/oxidation processes. The
      inhibitory effects of L-NAC and D-NAC on topo-IIa activity, in contrast to the
      other two thiols, may be due in part to the presence of amine groups which could
      allow for their participation in polyamine related processes. The difference in
      the magnitude of the effect exhibited by L-NAC, as compared to D-NAC, on the
      repression topo-IIa activity also suggests a role for GSH in this process.
      Inhibition of cellular progression and proliferation by thiols can therefore be
      mediated by diverse mechanisms which include both cycle-phase specific (i.e. L
      NAC and D-NAC) and non cell cycle specific (i.e. captopril) processes.

PMID- 9925992
TI  - Silent cerebral lesions on magnetic resonance imaging in subjects with coronary
      artery disease.
AB  - MRI of subjects with silent intracranial damages may provide more evidence than
      CT. Our objectives were to determine the prevalence of silent MRI lesions in
      patients with coronary artery disease. The study included 72 consecutive patients
      with angiographically proven coronary artery disease and 26 age and sex matched
      controls with normal coronary angiography. All subjects were evaluated for
      coronary atherosclerosis (Gensini and coronary angiography scores), the number of
      silent cerebral lesions detected by MRI, carotid stenosis and the risk factors
      for stroke. Thirty one of 72 (43.0%) patients had silent brain lesions on MRI
      while 8 of 26 (30.7%) control subjects showed silent brain infarction. The main
      finding on T2-weighted MRI was white matter hyperintensities (WMH) which were
      seen in all patients with silent brain lesions. The mean age of the patients with
      coronary artery disease and with silent cerebral lesions was significantly higher
      than that of patients without silent brain lesions. The Gensini score, coronary
      angiography score and prevalence of carotid stenosis are significantly higher in
      patients with silent cerebral lesions than that of patients without silent
      cerebral lesions. There was no significant difference between silent cerebral
      lesions and the other risk factors for stroke. Silent brain lesions are a common
      complication in patients with coronary artery disease. In patients with coronary
      artery disease, carotid artery stenosis and age were important risk factors for
      the development of silent brain infarction.

PMID- 9925993
TI  - A comparison of electrophysiologic properties between responders and non
      responders to DL-sotalol among patients with ventricular tachyarrhythmia.
      Importance of the lack of a reverse use-dependent effect on ventricular
      refractoriness to responders.
AB  - This study was undertaken to determine whether dl-sotalol can prevent ventricular
      tachyarrhythmia inducibility that can be predicted from electrophysiologic
      parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia
      (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic
      studies before and after dl-sotalol (320 mg/day). In 9 of 16 patients (56%) after
      dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire
      stimulation protocol (responders). There were significant differences in QT
      interval (462 +/- 52 vs. 415 +/- 34 msec; p < 0.05) and ventricular effective
      refractory period (VERP) at 600, 400 and 300 msec (302 +/- 28 vs. 262 +/- 20
      msec; p < 0.001, 280 +/- 23 vs. 240 +/- 21 msec; p < 0.001, 256 +/- 24 vs. 222 +/
      12 msec; p < 0.005, respectively) between responders and non-responders. The
      percentile increases in VERP (% VERP) at 600, 400, and 300 msec in responders
      were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%,
      respectively. Isoproterenol administered to responders did not fully reverse the
      dl-sotalol-induced prolongation of VERP (delta VERP) at 600, 400, and 300 msec,
      which remained significantly prolonged compared to the baseline (281 +/- 18 vs.
      241 +/- 16 msec; p < 0.01, 258 +/- 20 vs. 223 +/- 21 msec; p < 0.01, 247 +/- 22
      vs. 202 +/- 16 msec; p < 0.01, respectively). % VERP did not exhibit significant
      differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a
      reverse use-dependency. The results suggest that delta VERP in responders did not
      show reverse use-dependency, and that the phenomenon may account for the efficacy
      of dl-sotalol.

PMID- 9925994
TI  - Anatomically guided radiofrequency catheter ablation of atrial reentrant
      tachycardia.
AB  - Atrial reentrant tachycardia (ART) was ablated in an anatomically guided
      approach. Five patients with ART underwent 2 linear incisions without careful
      pace or activation mapping. One line was from an atrial activation site earlier
      than P wave onset to the nearest fixed anatomic conduction barrier, i.e., the
      inferior vena cava or coronary sinus ostium. The other line was made just above
      or closely crossed the first line vertically. Mean application time was 29 +/- 19
      minutes, and the application energy was 14,001 +/- 12,322 joules. Mean follow-up
      after ablation was 15 +/- 10 months. Three patients underwent electrophysiologic
      study three months after and sustained ART was not induced. All patients were
      free of sustained tachycardia events without antiarrhythmic drugs during the
      postoperative clinical course. Although anatomically guided ablation for ART
      requires much time and energy, it is easily and effectively done without careful
      activation or pace mapping, and is indicated if ablation using activation mapping
      or entrainment technique fails to cure the ART.

PMID- 9925995
TI  - Should digoxin be proscribed in elderly subjects in sinus rhythm free from heart
      failure? A population-based study.
AB  - Increased mortality in digoxin-treated subjects has been demonstrated in patients
      with recent myocardial infarction. Those with congestive heart failure (CHF) due
      to causes other than myocardial infarction seem to be free from this effect. No
      information is currently available concerning mortality in elderly people who are
      frequently prescribed digitalis even in the absence of CHF. The aim of this study
      was to investigate whether subjects improperly receiving digoxin were worse off
      than those not receiving this drug. This analysis is a part of CASTEL, a
      population-based prospective study that has enrolled a cohort of 2,254 subjects
      aged > or = 65 years. CHF was diagnosed in 187 subjects and atrial fibrillation
      (AF) in 90. The remaining 1,977 were free from CHF and in sinus rhythm, but 447
      were treated with digitalis. Cumulative mortality and morbid events by digitalis
      treatment were calculated in all these categories. Among subjects free from CHF
      and AF (improper use), all-cause and cardiovascular mortality was significantly
      higher among those taking digitalis than in those who did not. Non-fatal events
      including CHF were also more apparent in the former than in the latter. Cox
      analysis confirmed digitalis as a predictor of mortality in these subjects. No
      effect of digitalis on survival was found in patients with CHF or AF (proper
      use). In elderly subjects without atrial fibrillation or CHF, the use of
      digitalis worsens morbidity and mortality.

PMID- 9925996
TI  - Isovolumic relaxation flow in patients with left bundle branch block and normal
      coronary arteriogram.
AB  - The purpose of this study was to clarify the presence of isovolumic relaxation
      flow in patients with left bundle branch block and normal coronary arteriogram.
      Twenty-four patients with left bundle branch block and normal coronary
      arteriogram were examined by pulsed Doppler echocardiography and were compared
      with 20 age- and gender-matched healthy subjects. Impaired left ventricular
      relaxation was found in patients with LBBB. All 24 study patients showed
      isovolumic relaxation flow, but only 4 healthy subjects had isovolumic relaxation
      flow (p < 0.05). Peak velocity of the isovolumic relaxation flow ranged from 20
      42 cm/s. In the study group, left ventricular systolic function was normal in 17
      patients, and reduced in the remaining patients. At the end of this study, the
      presence of isovolumic relaxation flow which may be due to an abnormal septal
      motion was found in patients with left bundle branch block and normal coronary
      arteriogram.

PMID- 9925997
TI  - Oxygen utilization and hemodynamic response during exercise in children after
      Fontan procedure.
AB  - Eight patients, 9.1 to 16.5 years of age, were studied 2.8 to 8.5 years after
      Fontan operation. Oxygen utilization was determined during upright bicycle
      exercise. The cardiac index and stroke index were measured by echocardiography
      and the anaerobic threshold was determined. The results were compared with 10
      patients after surgical closure of the atrial septal defect. Anaerobic threshold
      (AT) in Fontan patients was lower than in the control subjects. Oxygen
      consumption at each stage of exercise was significantly lower in the Fontan group
      compared with the control subjects. From the beginning of exercise until AT, the
      increase in stroke index was lower in the Fontan patients than in the control
      subjects. After that point, the stroke index decreased significantly in the
      Fontan patients while it remained almost at the same level in the control
      subjects. Significant correlations were observed between the oxygen pulses and
      the stroke index at AT both in the control and Fontan groups. These results
      suggest that impaired exercise capacity in Fontan patients is mainly due to a
      subnormal response of the stroke index at AT and to the decreased response of the
      stroke index and the heart rate at the maximal workload.

PMID- 9925998
TI  - Pulmonary artery growth after systemic-to-pulmonary shunt in children with a
      univentricular heart and a hypoplastic pulmonary artery bed. Implications for
      Fontan surgery.
AB  - The aim of the study was to investigate the developmental pattern of hypoplastic
      pulmonary artery (p.a.) bed augmented by systemic-to-pulmonary shunt in children
      with univentricular heart scheduled for Fontan surgery. For the study, a highly
      selected patient cohort was chosen (12 patients aged between 5 and 19 years; mean
      9.5 years) with comparable initial morphological conditions of univentricular
      heart and hypoplastic p.a. bed, who after mandatory systemic-to-pulmonary shunt
      underwent Fontan procedure at time of normalization of pulmonary artery size.
      Further selection criteria were: normal pulmonary vascular resistance at time of
      Fontan procedure, competent a-v valve(s), and globally unimpaired ventricular
      function. All patients were grouped according to the preoperative pulmonary flow
      index (Qpi; L/min/m2 b.s.a.) measured immediately before Fontan operation: Group
      A: 1.5-2.5; B: 3.0-4.0; C: 4.0-5.0; D: > 6.0, and their cardio-pulmonary
      hemodynamic situation (Hb, SAsat%, Qp/Qs, PAP, Rp/Rs, EDVP, FS%, ventricular
      diastolic compliance (VC = EDVP/Qpi + Qsi) as well as the pulmonary artery size
      and area using standard (Nakata-index, McGoon-ratio) and a self designed computer
      assisted planimetric area calculation (PPAAI; cm2/m2 b.s.a.) analysed. Each
      patient underwent 1-3 shunt procedures, the mean shunt patency period for groups
      A, B, C and D was 12, 8.6, 5.3, and 4.5 years, respectively. The mean Nakata
      index (283, 297, 324, 405 in groups A-D) and the McGoon-ratio (2.0, 2.2, 2.8, 3.3
      in groups A-D) correlated with the Qp index, reflecting flow dependent
      development of pulmonary artery bed. No correlation was found between Qpi and
      PPAAI (47, 40, 41 and 47 in group A-D). The VC/Qp relation showed an inversely
      proportional pattern with values 2.3, 1.0, 0.8, 0.7 for corresponding groups A-D,
      the lowest VC in group A correlated with polyglobulic status (Hb- values; g/dl):
      21.3 in A vs 19.8, 18.0 and 16.5 in B-D) and mean arterial SAsat-values (77% in A
      vs 83%, 84% and 89% in B-D). In conclusion, in our highly selected patient
      cohort, the development of p.a. size was strongly flow-dependent, and patients
      with restrictive pulmonary flow needed an approximately threefold longer time
      period to normalize their p.a. size compared to those with excessive flow. In
      patients with restrictive pulmonary flow, the Nakata-index underestimated the
      degree of development of the pulmonary artery system, probably due to the
      distortion of the proximal p.a. segment. In consequence, in these patients the
      normalization of the p.a. bed and thus suitability for the Fontan procedure
      probably occurred much earlier. Based on our observations and those of others, in
      patients with excessive flow the normalization of p.a. bed, provided it occurs
      within 3-4 years, seems not necessarily to be associated with a deterioration of
      ventricular function.

PMID- 9925999
TI  - Molecular genetic diagnosis of a family with hypercholesterolemia by a mismatched
      PCR-RFLP method for genotyping single base substitution of the LDL receptor gene.
AB  - Plasma lipid and lipoprotein levels reflect in part the influence of relevant
      genetic loci. Defects at some of these loci account for specific types of
      dyslipoproteinemia occurring with regularity among family members. In the course
      of familial investigations of coronary artery disease, we identified an family in
      which several members were affected with elevated low density lipoprotein (LDL)
      cholesterol levels. To study the genetic defects responsible for plasma
      lipoprotein abnormality in this pedigree, we developed a simple method for
      genotyping a single base substitution that does not affect a restriction
      recognition enzyme site in exon 10 of the LDL receptor gene. Using our mismatched
      PCR method, this G- > A substitution at nucleotide 1413 could be genotyped in the
      form of a biallelic restriction fragment length polymorphism (RFLP) after
      digestion with restriction enzyme Hpa II. Linkage analysis using this molecular
      method demonstrated that the defect at the LDL receptor locus is responsible for
      elevated LDL cholesterol phenotype observed in this family by segregation of
      defective alleles at the LDL receptor locus with the disease (peak decimal
      logarithm of odds score > 3.0).

PMID- 9926000
TI  - Discordant prolongation of the refractory period and repolarization time by a
      class III agent, E4031, in the healing phase of myocardial infarction.
AB  - Susceptibility to reentrant tachyarrhythmias and the antiarrhythmic efficacy of
      class III agents are related more to the duration of the refractory period (ERP)
      than to the repolarization time (RT). We measured both ERP and RT in a canine
      model of healing myocardial infarction, and evaluated the effect of a class III
      agent (E4031) on these parameters and on the inducibility of ventricular
      tachyarrhythmias. ERP and RT on the unipolar electrogram were measured at several
      cycle lengths in the normal (NZ) and infarct zones (IZ), respectively, in 10
      canine myocardial infarction models and extrastimulation was used to induce
      ventricular arrhythmias. Measurements were repeated after E4031 administration.
      At baseline, both ERP and RT were significantly longer in IZ than in NZ with
      ERP/RT ratio also higher in IZ. This ratio tended to increase at longer cycle
      lengths. E4031 increased ERP and RT both in NZ and IZ at all cycle lengths, but
      increased the ERP/RT ratio predominantly in IZ. E4031 prevented induction of
      sustained VT or VF, which was inducible in 3 out of 10 dogs at baseline, although
      it facilitated induction of VF in 1 dog with no baseline arrhythmia. By
      increasing the ERP/RT ratio, class III drugs may shorten the relative refractory
      period in IZ at the expense of a greater ERP difference created between NZ and
      IZ.

PMID- 9926001
TI  - Rearrangement of the ventricular capillary network in stroke-prone spontaneously
      hypertensive rats (SHRSP) following a late start of treatment with the
      angiotensin converting enzyme blocker temocapril.
AB  - The effects of the angiotensin converting enzyme (ACE) blocker temocapril on the
      capillary network of the left ventricle were studied in stroke-prone
      spontaneously hypertensive rats (SHRSP). The ACE blocker was dissolved in the
      drinking water and supplied to 24 and 32 week old SHRSP ad libitum for 5 weeks.
      The capillaries of the wall of the left ventricle were studied using a double
      staining method to differentiate the arteriolar, intermediate and venular
      capillary portions. Capillary density increased and capillary domain areas
      decreased in all capillary portions compared with untreated control SHRSP in both
      age groups. The proportion of venular capillary portions was increased by
      temocapril treatment. The results indicate that the late start of ACE blockade
      caused the regression of the hypertrophied cardiomyocytes, which is
      characteristic of SHRSP, and the rearrangement of capillary portions. The plasma
      concentration of angiotensin II was significantly lower in temocapril-treated
      SHRSP compared to the control group. The implication is that intrinsic
      angiotensin II exerts an appreciable effect on the function, structure and
      capillary network in the left ventricular wall in SHRSP.

PMID- 9926002
TI  - Judicious antimicrobial-use principles, related proposals approved by board.

PMID- 9926003
TI  - Screwworm returns to vex Texas.

PMID- 9926004
TI  - AAHA adopts position statement on ear cropping and tail docking of dogs.

PMID- 9926006
TI  - What is your diagnosis? Nodular lung disease.

PMID- 9926005
TI  - What is your diagnosis? Intestinal ileus and dilatation.

PMID- 9926007
TI  - Theriogenology question of the month. The goat is pseudopregnant (hydrometra).

PMID- 9926008
TI  - Compendium of animal rabies control, 1999. The NASPHV Committee.

PMID- 9926009
TI  - Efficacy of etodolac for the treatment of osteoarthritis of the hip joints in
      dogs.
AB  - OBJECTIVE: To assess the efficacy of etodolac in improving hind limb function in
      dogs with osteoarthritis of the hip joint. DESIGN: Prospective study. ANIMALS:
      100 client-owned dogs with clinical signs of osteoarthritis of the hip joint.
      PROCEDURE: Baseline ground reaction forces and subjective assessment scores were
      collected twice at a 7- to 10-day interval. After meeting entrance criteria, dogs
      were randomly assigned to the following 3 treatment groups: control group (0 mg
      of etodolac), low-dosage group (135 mg of etodolac), or high-dosage group (450 mg
      of etodolac). Dogs were treated once daily for 8 days, and gait analysis was
      repeated on day 8. RESULTS: On day 8 of treatment, vertical impulse and vertical
      peak force values for low- and high-dosage groups were significantly greater than
      baseline values within each group. On day 8, vertical impulse values from the
      high-dosage group were significantly greater than values from the low-dosage
      group. Vertical peak forces for the low- and high-dosage groups were
      significantly greater at 8 days than that of the control group. Analysis of the
      effect of evaluation center (site) on treatment outcome did not reveal a
      significant effect. CLINICAL IMPLICATIONS: Etodolac administration for 8 days
      improved ground reaction forces in dogs with osteoarthritis of the hip joint.
      Improvement in force transmission was dosage dependent for the primary outcome
      measurement (vertical impulse). Results of the study indicate that etodolac is
      well tolerated by dogs, with minimal adverse effects during an 8-day treatment
      period.

PMID- 9926010
TI  - Symmetric cutaneous necrosis of the hind feet and multicentric follicular
      lymphoma in a cat.
AB  - A 7-year-old castrated male domestic shorthair cat was admitted to the veterinary
      teaching hospital for evaluation of symmetric necrosis of the skin of its hind
      feet and high liver enzyme activities. Lymphoma was diagnosed on cytologic
      examination of a fine needle aspirate of the liver. The owner declined treatment
      for the lymphoma. On postmortem histologic examination, lymphoma was found in the
      liver, stomach, and multiple lymph nodes. Immunohistochemical staining revealed
      the neoplasm to have a mixed B- and T-cell follicular arrangement, and a
      diagnosis of multicentric follicular lymphoma was made. The distal portion of the
      feet were necrotic, but a neoplastic infiltrate was not seen on histologic
      examination. After thrombosis and vasculitis were excluded as causes, the
      ischemic necrosis of the feet of the cat in this report was considered a
      paraneoplastic syndrome, as can be seen in people with lymphoma or other internal
      malignancies.

PMID- 9926011
TI  - Primary corneal papilloma and squamous cell carcinoma associated with pigmentary
      keratitis in four dogs.
AB  - Squamous cell carcinoma (SCC) and squamous papilloma are rarely reported as
      primary lesions of the cornea in dogs. One case of corneal papilloma and 3 cases
      of SCC, each arising as a primary central corneal neoplasm rather than spreading
      from adjacent limbal conjunctiva, were reviewed. The most common cause of SCC in
      animals is chronic exposure of lightly pigmented epithelium to UV light; however,
      all dogs in this study had a history of chronic pigmentary keratitis. Three of
      the 4 dogs were of brachycephalic breeds with naturally proptotic eyes and
      oversized palpebral fissures that may have exposed the cornea to greater
      excessive solar radiation. Alternatively, mechanical factors that caused chronic
      changes in the cornea may have been causative factors for induction of primary
      dysplastic or neoplastic changes. Primary corneal neoplasia should be considered
      in the differential diagnosis of corneal masses.

PMID- 9926012
TI  - Clinicopathologic features of dogs with hepatic microvascular dysplasia with and
      without portosystemic shunts: 42 cases (1991-1996).
AB  - OBJECTIVE: To identify and compare clinicopathologic features between dogs with
      hepatic microvascular dysplasia (HMD) and confirmed portosystemic shunts (PSS)
      and dogs with HMD alone and to determine whether any discriminating variables can
      be identified to differentiate the conditions. DESIGN: Retrospective study.
      ANIMALS: 42 dogs with HMD. PROCEDURE: Medical records of dogs with HMD examined
      between January 1991 and October 1996 at 3 veterinary hospitals were reviewed.
      RESULTS: Compared with dogs with PSS and HMD, dogs with HMD alone were older and
      had higher values for mean corpuscular volume (MCV) and serum total protein,
      albumin, creatinine, cholesterol, BUN, and blood glucose concentrations. Compared
      with dogs with HMD alone, dogs with PSS and HMD had higher values for pre- and
      postprandial serum bile acid concentrations, WBC, and serum alkaline phosphatase
      and aspartate aminotransferase activities. The most discriminating variables for
      the 2 conditions were serum postprandial bile acid concentrations, MCV, and serum
      albumin and cholesterol concentrations. CLINICAL IMPLICATIONS: The discriminant
      variables of postprandial serum bile acid concentrations, MCV, and serum albumin
      and cholesterol concentrations may be useful in distinguishing between dogs with
      HMD alone and dogs with PSS and HMD.

PMID- 9926013
TI  - Endoscopy of the intertubercular bursa in horses.
AB  - Forelimbs from 3 anesthetized horses and 16 fresh cadaver horses were used to
      describe the endoscopic anatomy of the intertubercular bursa and outline the
      surgical portals that provide the greatest access to structures within the bursa.
      A lateral arthroscopic portal was made proximal to the deltoid tuberosity of the
      humerus into the distal bursal recess. A second portal was created proximal to
      the humeral tubercles that entered the proximal bursal space. These approaches
      provided consistent viewing and instrument access to the lateral intertuberal
      groove, the greater and intermediate humeral tubercles, and the synovial membrane
      of the proximal and distal bursal recesses. The intermediate tubercle and heavy
      muscle mass restricted access to the medial intertuberal groove and lesser
      tubercle. This technique may provide a less invasive alternative to bursotomy in
      the surgical management of selected horses with intertubercular bursitis.
      Clinical applications include cartilage debridement, fragment removal, partial
      synovectomy, and high-volume lavage.

PMID- 9926014
TI  - Incarceration of the small colon through a rent in the gastrosplenic ligament in
      a pony.
AB  - A 10-year-old castrated male pony was examined for intermittent signs of
      abdominal pain of 3 days' duration. An incarceration of the small colon through a
      rent in the gastrosplenic ligament was found. Resection and end-to-end
      anastomosis were performed on the affected portion of the small colon. The pony
      recovered and returned to its previous degree of activity. Incarceration of the
      small intestine and large colon through rents in the gastrosplenic ligament are
      documented, although involvement of the small intestine is more common. To the
      best of our knowledge, incarceration of the small colon has not been reported.
      Although a rare event, incarceration of the small colon in the gastrosplenic
      ligament should be considered in the differential diagnosis list for horses with
      intermittent signs of abdominal pain.

PMID- 9926015
TI  - Association of Clostridium difficile with enterocolitis and lactose intolerance
      in a foal.
AB  - Diagnoses of Clostridium difficile enterocolitis and lactose intolerance were
      made in a neonatal foal with persistent diarrhea. It was determined that the foal
      had lactose intolerance on the basis of the results of a lactose tolerance test,
      and a diagnosis of C difficile enterocolitis was subsequently made. The foal
      responded to oral administration of metronidazole and lactase. Lactose
      intolerance is a secondary problem most commonly associated with rotavirus
      infection, but it can be caused by any condition affecting the small intestine.
      Because C difficile can affect the small intestine in foals, it was presumably
      the cause of the lactose intolerance in this foal with persistent diarrhea. Oral
      administration of lactase was not initially successful in this foal, most likely
      because of ongoing C difficile enterocolitis. Presumably, metronidazole was an
      effective treatment for C difficile enterocolitis and administration of lactase
      allowed for normal digestion of milk until endogenous lactose production
      returned. Clostridium difficile enterocolitis and lactose intolerance should be
      considered as differential diagnoses in neonatal foals with diarrhea, especially
      when the foal is bright and alert.

PMID- 9926016
TI  - Evaluation of enterolithiasis in equids: 900 cases (1973-1996).
AB  - OBJECTIVE: To identify breed, age, sex, physical findings, history, and outcome
      of treatment in horses and other equids with enterolithiasis. DESIGN:
      Retrospective study. ANIMALS: 900 equids with enterolithiasis. PROCEDURE: Medical
      records from equids with enterolithiasis admitted between 1973 and 1996 were
      reviewed. Data on signalment, history, physical examination and clinicopathologic
      findings, surgical findings, and outcome were compiled from records and from
      telephone interviews with owners. Sex and breed predilections were determined by
      comparison of the study population with the general hospital population of equids
      during the same time period. RESULTS: Equids with enterolithiasis represented
      15.1% of patients admitted for treatment colic, and 27.5% of patients undergoing
      celiotomy for treatment of colic. Arabian and Arabian crosses, Morgans, American
      Saddlebreds, and donkeys were significantly overrepresented, and Thoroughbreds,
      Standardbreds, warmbloods, and stallions were significantly underrepresented in
      the study population, compared with the hospital population. The mean age of
      equids with enterolithiasis was 11.4 years. The most common historic findings
      were signs of intermittent colic (33.3%) and passage of enteroliths in the feces
      (13.5%). Physical examination findings were similar to those found in equids with
      other forms of nonstrangulating large colon obstructive disease. Fifteen percent
      (131) developed gastrointestinal tract rupture caused by an enterolith that
      necessitated euthanasia. Short-term and 1-year survival rates for equids
      undergoing celiotomy for treatment of enterolithiasis and recovering from
      anesthesia were excellent (96.2 and 92.5%, respectively), and postoperative
      complications were uncommon. Recurrence of enterolithiasis was identified in 7.7%
      of the study population. CLINICAL IMPLICATIONS: Results indicated that shortterm
      and 1-year survival rates for equids undergoing surgery for enterolithiasis are
      excellent. Identification of signalment, history, and management factors may help
      identify equids with a high risk for development of enterolithiasis.

PMID- 9926017
TI  - Attitudes of veterinary medical students, house officers, clinical faculty, and
      staff toward pain management in animals.
AB  - OBJECTIVE: To determine whether animal factors and level of professional
      veterinary medical training were associated with attitudes toward pain management
      in animals. DESIGN: Exploratory, descriptive survey. SAMPLE POPULATION: Students
      in the College of Veterinary Medicine and Biomedical Sciences professional
      veterinary medical curriculum (approx 540) and clinical faculty (approx 50),
      house officers (approx 25), and support staff (approx 100) in the Colorado State
      University Veterinary Teaching Hospital. PROCEDURE: A descriptive survey
      including demographic, descriptive, and case-based questions was distributed to
      participants. Participation was voluntary and survey results were anonymous.
      RESULTS: 357 of 720 surveys were completed and returned (31 by faculty, 29 by
      staff, 18 by house officers, and 279 by students). There was a high degree of
      concordance among survey participants regarding the overall importance of
      treating pain in animals. The extent to which pain should be alleviated and
      animal factors, such as breed, behavior, and clinical circumstances, accounted
      for much of the discordance among survey groups. Fourth-year veterinary students
      indicated that they were occasionally less likely to treat animals for pain than
      were second- or third-year veterinary students. CLINICAL IMPLICATIONS: The
      diversity of opinions regarding the necessity or desirability of treating pain in
      animals, the apparent decrease in the likelihood of senior veterinary students to
      treat animals for pain under certain circumstances, and evidence of knowledge
      deficits regarding analgesic treatments among all groups contribute to the
      likelihood that pain in animals will neither be consistently recognized nor
      appropriately treated.

PMID- 9926018
TI  - [Image of the month. Symphysis pubis diastasis syndrome].

PMID- 9926019
TI  - [Pharma clinics. How I treat...a diabetic patient with severe obesity].
AB  - Obesity plays a crucial role in type 2 diabetes pathophysiology and a major
      weight loss markedly improves glycaemic control. The common failure of classical
      treatments leads to the use of more aggressive weight-reduction approaches, such
      as very-low-calorie diets (VLCDs), anti-obesity drugs or even bariatric surgery.
      VLCDs are very successful in the short-term but rather disappointing in the long
      term. Anti-obesity compounds only induce a modest mean weight reduction, even if
      some patients appear to be better responders. Interestingly, serotoninergic
      agents increase insulin sensitivity and glycaemic control, independently of
      weight loss. Bariatric surgery provides the most impressive results. In well
      selected subjects, gastroplasty (either vertical ring gastroplasty or adjustable
      silicone gastric banding) generally induces a considerable weight loss which
      results in a remarkable and sustained glycaemic control improvement and allows
      the reduction, or even the suppression, of any antidiabetic treatment. This
      ultimate solution should not be neglected after failure of medical approaches,
      provided that the indication is correct, the surgical procedure is performed in a
      specialized centre and the followup is well organized by a multidisciplinary
      team.

PMID- 9926020
TI  - [Clinical case of the month. A case of Munchausen syndrome (factitious
      disorder)].
AB  - Factitious disorders are characterized by physical or psychological symptoms that
      are intentionally produced or feigned in order to assume the sick role. In the
      particularly severe type presented by Munchausen syndrome, the person's entire
      life may consist of either trying to get admitted to or staying in hospitals.
      From the case of a 47 year old patient exhibiting symptoms of neurological aspect
      associated with psychological complaints, the issue of differential diagnosis of
      a factitious disorder is addressed. The integration of the reported
      symptomatology to the subject's personal history seems indispensable to the
      understanding and the global therapy of the patient.

PMID- 9926021
TI  - [The Emperor's New Clothes syndrome. Description of a new epidemic].
AB  - In 1971, F. Gross, inspired by "The Emperor's new clothes" (H.C. Andersen--1835),
      published in the New England Journal of Medicine, a report of an endemic
      polysystem disease: the emperor's clothes syndrome. In the first place, it
      touches students or physicians who fear losing their prestige. From personal
      observations, we describe a new epidemic of this disease whose radiological image
      is the main vector. By this comment, we wish to attract the attention to the
      danger of giving a diagnosis uniquely on the basis of the complementary
      examinations. We want to underline the importance of the medical history and
      physical examination. All clinical or radiological data, all biological
      phenomenons are subject to variable interpretation. There exist statistical
      methods to estimate the sensitivity, the specificity and the clinical value of a
      test.

PMID- 9926022
TI  - [Cardiac pacemakers and cellular phones].
AB  - Digital cellular phones pose a potential risk of temporary pacemaker dysfunction.
      However, this risk could be dramatically reduced using simple patients
      recommendations and careful programming of sensing parameters.

PMID- 9926023
TI  - [Sugar diabetes. Update elements].
AB  - The various types of diabetes mellitus are now more precisely classified
      according to their etiopathogenies. Therefore, type 1 (autoimmune or not), type
      2, gestational diabetes, as well as MODY (Maturity Onset-Diabetes of the Young)
      and secondary diabetes are considered as separate entities. Any type of diabetes
      brings its set of complications. Biological chemistry is directed to define the
      etiopathogenic characteristics of the various types of diabetes and to assess the
      severity of metabolic and functional disturbances. Diagnostic criteria in term of
      glycemia have also been reviewed to asses diabetes and glucose intolerance.

PMID- 9926024
TI  - [Hypnosis and its application in surgery].
AB  - Since 1992, we have used hypnosis routinely in more than 1400 patients undergoing
      surgery. We found that hypnosis used in patients as an adjunct to conscious
      sedation and local anesthesia was associated with improved intraoperative patient
      comfort, and with reduced anxiety, pain, intraoperative requirements for
      anxiolytic and analgesic drugs, optimal surgical conditions and a faster recovery
      of the patient. We reported our clinical experience and our fundamental research.

PMID- 9926026
TI  - [Starling's law in 1998].
AB  - This paper reexamines the law of Starling on the exchanges of liquids through the
      capillaries at the light of the most recent data available in the literature.

PMID- 9926025
TI  - [Use of ionizing radiation to prevent restenosis in interventional cardiology].
AB  - Recently, the use of ionizing radiations has received much interest as a new
      treatment tool to reduce restenosis after angioplasty or stent implantation.
      There are two main approaches for delivering endovascular radiation: one is based
      on gamma or beta sources with very high activities to deliver locally through a
      catheter the dose in a limited period of time. The other approach is based on a
      stent rendered radioactive for long exposure and continuous low-dose rate
      treatment. External radiation is also contemplated but indications seem more
      oriented towards the peripheral vascular system. After a brief introduction to
      fundamentals of radiobiology, radiation physics and radioprotection, we review
      the experimental data which have led to large ongoing multicenter trials. The
      results of these trials involving more than 2000 patients will be available in
      the next few years and will allow to better define the risk/benefit ratio of this
      potentially new indication for radiotherapy.

PMID- 9926027
TI  - [Endovascular treatment of supra-aortic stenosing lesions].
AB  - After a description of the endovascular procedure for the treatment of supra
      aortic trunks lesions, the author, through an international review of the
      literature, analyses the feasibility and the results of this recent surgical
      technique in comparison to conventional surgery.

PMID- 9926028
TI  - [Pathogenesis of IgA nephropathies].
AB  - The loss of kidney function in IgA nephropathy results from matrix overproduction
      by mesangial cells stimulated by IgA circulating complexes (IgA-CC) deposited in
      the mesangial area. High IgA-CC plasma concentrations are at least partly
      secondary to a genetically induced overproduction of undergalactosylated IgA
      molecules poorly cleared by the liver.

PMID- 9926029
TI  - Overcoming obstacles to routine outcome measurement. The nuts and bolts of
      implementing clinical audit.

PMID- 9926030
TI  - Hair analysis. New laboratory ability to test for substance use.

PMID- 9926031
TI  - Psychological treatment of depression in children and adolescents. A review of
      treatment research.
AB  - BACKGROUND: This paper reviews research on the psychological treatment of
      depression in children. METHOD: Manual and computer literature searches were
      performed. RESULTS: The most promising psychological interventions for depression
      in children are individual rather than family therapies. Cognitive--behavioural
      therapy seems to be an effective treatment for depressive symptoms and mild
      depressive disorders. It may also be a useful preventive intervention, though
      this remains to be conclusively demonstrated. There have been no systematic
      studies comparing psychological treatments with medication. CONCLUSIONS: Studies
      comparing psychological treatments and medication are now required.

PMID- 9926032
TI  - Neuroimaging in autism.
AB  - BACKGROUND: Childhood autism is a developmental disorder with distinctive
      clinical features and characteristic cognitive deficits. Neuroimaging techniques
      have been extensively used in the study of autism and related disorders. METHOD:
      Recent important literature reported on structural and functional neuroimaging in
      autism was reviewed and discussed in the context of other neurobiological
      research findings. RESULTS: Various abnormalities of brain structure and function
      have been proposed, but no focal defect has been reliably demonstrated. Important
      findings, so far, include increased brain volume, structural abnormality in
      frontal lobe and corpus callosum in a proportion of autistic individuals.
      Functional neuroimaging findings emphasised the imbalance in inter-regional and
      inter-hemispheric brain metabolism and blood flow as well as abnormality in the
      anterior cingulate gyrus. CONCLUSION: The research to date has been hindered by
      methodological difficulties. However, hypothesis-driven research, particularly
      involving activation studies and neurotransmitter/neuroreceptor activities, using
      functional neuroimaging will be very useful in unravelling the enigma associated
      with this intriguing and distressing condition.

PMID- 9926033
TI  - Nuclear schizophrenic symptoms as a window on the relationship between thought
      and speech.
AB  - BACKGROUND: Symptoms of schizophrenia known as 'nuclear' or 'first-rank' are
      found in all populations. The genetic variation that gives rise to them must be
      as old as modern Homo sapiens. METHOD: The hypothesis was formulated that
      language evolved, under constraints on callosal transmission, by a process of
      hemispheric specialisation. One component, the phonological output sequence,
      became localised to the dominant hemisphere whereas its associations (the
      signifieds) were lateralised in part to the non-dominant hemisphere. Concepts
      ('thoughts') are translated through a bi-hemispheric interaction into phonemes
      ('speech') by the speaker in frontal association areas, and decoded back into
      concepts ('meanings') by the hearer in occipitotemporo-parietal association
      areas. RESULTS: The first-rank symptoms demonstrate that an integral component is
      a system of 'indexicality' that distinguishes those phonemic signals generated by
      the hearer, from his own thoughts, and from signals that he receives from an
      interlocutor. CONCLUSIONS: Language, as Buehler proposed, is cast in a coordinate
      system orientated at its origin, in the dominant hemisphere, to the self of the
      speaker. Thus conceived, the phenomena of the illness called schizophrenia are
      key to the neural organisation of the human characteristic of language.

PMID- 9926034
TI  - Invited commentaries on: nuclear schizophrenic symptoms as a window on the
      relationship between thought and speech.

PMID- 9926035
TI  - Typology of common psychiatric syndromes. An empirical study.
AB  - BACKGROUND: Diagnostic comorbidity is prevalent in psychiatry and may be
      inadequately captured by the DSM-III/III-R nosology. METHODS: The lifetime
      presence of II psychiatric diagnoses was determined by structured personal
      interviews of a population-based sample of 1898 female twins. We used latent
      class analysis to derive an empirical typology. RESULTS: Six classes provided the
      best fit to the data. Their mnemonics were: minimal disorder (60% of the sample),
      major depression-generalised anxiety disorder (19%), alcohol-nicotine (7%),
      highly comorbid major depression (5%) and eating disorders (3%). The validity of
      this typology was strongly supported by demographic, health, personality and
      attitudinal validators along with the significant monozygotic twin concordance
      for class membership. The typology superficially resembled DSM-III-R, but
      contained many differences. Major depression appeared in three forms (alone, with
      generalised anxiety disorder and with considerable comorbidity). Alcoholism
      nicotine dependence and the various anxiety disorders formed discrete classes,
      but were also prominent in other classes. Bulimia and anorexia were exceptional
      in their appearance in a single class. CONCLUSIONS: The DSM-III-R and closely
      related DSM-IV nosology did not capture the natural tendency of these disorders
      to co-occur. Fundamental assumptions of the dominant diagnostic schemata may be
      incorrect.

PMID- 9926036
TI  - Methods used for suicide by farmers in England and Wales. The contribution of
      availability and its relevance to prevention.
AB  - BACKGROUND: Farmers in the UK have an elevated risk of suicide. It has been
      suggested that this may be related to their ease of access to dangerous means for
      suicidal behaviour. The extent to which farmers use these means and changes in
      their use may be relevant to suicide prevention. METHOD: Data on 719 deaths in
      farmers of both genders in England and Wales between 1981 and 1993 in which a
      verdict of suicide or undetermined cause (open verdict) was recorded were
      analysed. RESULTS: Of 702 deaths in male farmers, firearms were involved in
      40.0%, hanging in 29.6%, carbon monoxide in 16.4%, poisoning in 8.0% (over half
      of which involved agricultural or horticultural poisons) and other methods in
      6.1%. There was a considerable excess of deaths due to firearms compared with the
      distribution of methods of suicide and open verdict deaths in males in the
      general population. Hanging was also somewhat more frequent. During the study
      period there was a reduction in firearm death rates, particularly after 1989 when
      there was national legislation on firearm ownership, registration and storage.
      There were also fewer farming suicides after this date. By the end of the study
      period hanging was more frequent than deaths involving firearms. CONCLUSIONS:
      Farmers who commit suicide tend to use methods to which they have easy access.
      Restriction of the ready availability of such methods, particularly in farmers
      known to be depressed or otherwise at risk, might prevent some suicides.

PMID- 9926037
TI  - Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive
      anticholinergics over the course of a 10-year prospective study.
AB  - BACKGROUND: Although increased mortality is one of the most consistent and
      accepted epidemiological findings in schizophrenia, a high rate of suicide
      appears unable to account fully for this burden which remains poorly understood.
      METHOD: A cohort of 88 in-patients was followed prospectively over a 10-year
      period and predictors of survival sought among demographic, clinical and
      treatment variables. RESULTS: Over the decade, 39 of the 88 patients (44%) died,
      with no instances of suicide. Reduced survival was predicted by increasing age,
      male gender, edentulousness and time since pre-terminal withdrawal of
      antipsychotics; additionally, two indices of polypharmacy predicted reduced
      survival: maximum number of antipsychotics given concurrently (relative risk
      2.46, 95% CI 1.10-5.47; P = 0.03) and absence of co-treatment with an
      anticholinergic (relative risk 3.33, 95% CI 0.99-11.11; P = 0.05). CONCLUSIONS:
      Receiving more than one antipsychotic concurrently was associated with reduced
      survival, in the face of little or no systematic evidence to justify the
      widespread use of antipsychotic polypharmacy. Conversely, over-cautious attitudes
      to the use of adjunctive anticholinergics may require re-evaluation.

PMID- 9926038
TI  - Antecedents of suicide in people with schizophrenia.
AB  - BACKGROUND: Suicides among people with schizophrenia are commonly believed to be
      impulsive and to occur unexpectedly. METHOD: As part of the National Suicide
      Prevention Project in Finland, a nationwide psychological autopsy study, suicide
      victims with DSM-III-R schizophrenia (n = 86; n = 64 in the active illness phase)
      and others (n = 1109; n = 666 without any evidence for psychosis) were compared
      for communication of suicidal intent (CSI), as well as previous suicide attempts
      known by the next of kin and/or an attending health care professional during the
      latest treatment relationship. RESULTS: More victims with schizophrenia (84%) had
      a history of previous CSI, and/or had made previous suicide attempt(s) than
      others (70%). Also, victims with active illness schizophrenia (56%) had more CSI
      and/or had made suicide attempts during their last three months than victims with
      no psychosis (41%). CONCLUSIONS: CSI and/or suicide attempts occur at least as
      often in people with schizophrenia as in those without schizophrenia, even in the
      active phase of the illness.

PMID- 9926039
TI  - Utilisation of mental health services and costs of patients with schizophrenia in
      three areas of Spain.
AB  - BACKGROUND: The analysis of the costs of schizophrenia and its treatment under
      different mental health care structures will facilitate the improved allocation
      of the limited resources available for the treatment of schizophrenia. The
      research we present compares health service use and total health care costs of
      three cohorts of subjects with schizophrenia which are representative of three
      areas of Spain (Burlada in Navarra, Cantabria and the Eixample of Barcelona).
      METHOD: We selected first-time contacts with any psychiatric service who received
      a diagnosis of schizophrenia. Subjects were evaluated in the third year after
      onset. RESULTS: The mean number of out-patient visits per patient per year was
      10.7 and the mean in-patient days were 9.5. The mean direct cost per patient in
      the third year of treatment was US$2243. Costs were higher for single subjects
      and for people who had a relapse. Costs of subjects with better functioning were
      lower than costs of subjects with a worse state. CONCLUSIONS: Direct costs of
      care in Spain were lower than the reported figures from other western European
      countries. Costs were greater in the two centres with greater community mental
      health service development. Some of the findings may be explained by service
      availability.

PMID- 9926041
TI  - Cocaine use, abuse and dependence in a population-based sample of female twins.
AB  - BACKGROUND: Although cocaine use in women has increased substantially over the
      past half-century, we understand little about the aetiology in women of cocaine
      use and abuse, and know almost nothing about the role of genetic factors. METHOD:
      We obtained by telephone interview a history of lifetime cocaine use, abuse and
      dependence from 1934 individual twins from female-female pairs ascertained
      through a population-based registry, including both members of 485 monozygotic
      (MZ) and 335 dizygotic (DZ) pairs. RESULTS: The prevalence of lifetime cocaine
      use, abuse and dependence were 14.0%, 3.3% and 2.3%. Probandwise concordance
      rates, in MZ and DZ twins, respectively, were: cocaine use 54% and 42%; cocaine
      abuse 47% and 8% and cocaine dependence 35% and 0%. In MZ and DZ twins, odds
      ratios were: cocaine use 14.2 and 6.7 and cocaine abuse 40.8 and 2.7. Biometrical
      model-fitting suggested that twin resemblance for liability to cocaine use was
      due to both genetic and familial-environmental factors while twin resemblance for
      cocaine abuse and symptoms of dependence was due solely to genetic factors.
      Estimated heritabilities were: cocaine use 0.39, cocaine abuse 0.79 and symptoms
      of dependence 0.65. CONCLUSIONS: The vulnerability to cocaine use and
      particularly cocaine abuse and dependence in women is substantially influenced by
      genetic factors.

PMID- 9926040
TI  - Long-term pharmacokinetics of clozapine.
AB  - BACKGROUND: Previous studies of clozapine pharmacokinetics have shown a wide
      intra- and inter-individual variability of plasma levels in patients on stable
      clozapine doses. We investigated dose-plasma level relationships and intra
      individual variability of plasma levels during maintenance treatment with
      clozapine. METHOD: Forty-one patients on clozapine were followed for 26 weeks
      with repeated plasma level measurements and assessments of co-medication and
      clinical symptoms. In a second step, 15 patients on stable clozapine doses
      between treatment Weeks 12 and 52 were followed in the same way. Coefficient of
      variation was used as a parameter of plasma level deviation. RESULTS: Dose-plasma
      level correlations stayed significant from Week 6 to Week 26 (n = 41). The group
      of patients followed up to Week 52 showed a mean intra-individual coefficient of
      variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically.
      CONCLUSIONS: Even though clozapine plasma levels may show a significant degree of
      variation, this is not necessarily reflected in a change in psychopathology.

PMID- 9926042
TI  - Anti-androgenic agent cyproterone acetate cured a woman of severe sexual
      obsessions.

PMID- 9926043
TI  - Pisa syndrome during treatment with sertindole.

PMID- 9926044
TI  - Olanzapine-induced thrombocytopenia in association with idiopathic
      thrombocytopenic purpura.

PMID- 9926045
TI  - Salinophagia in anorexia nervosa.

PMID- 9926046
TI  - Fluoxetine and graded exercise in chronic fatigue syndrome.

PMID- 9926047
TI  - Chromosome 22qII deletions and aggressive behaviour.

PMID- 9926048
TI  - Slow progress in improving practice of electroconvulsive therapy.

PMID- 9926049
TI  - Whither community care?

PMID- 9926050
TI  - Benzodiazepines: time for reassessment.

PMID- 9926051
TI  - Rationale and design. PRiSM Psychosis Study I.
AB  - BACKGROUND: This paper sets out the rationale for the PRiSM Psychosis Study, and
      the research design used. Nine accompanying papers present the main results. The
      questions addressed by the PRiSM Psychosis Study are: can the gains of
      experimental studies which have demonstrated benefits arising from treatment by
      community mental health teams be translated to routine settings? If so, are the
      benefits diluted in ordinary clinical practice? What are the costs? METHOD: A
      prospective nonrandomised controlled trial of two types of community mental
      health service, in two phases: case identification followed by patient
      interviews. For the case identification the research team conducted the complete
      ascertainment of all prevalent cases of psychosis in the two study catchment
      areas in the index year (1991-1992). From all 514 patients with psychotic
      disorders thus identified, 302 were randomly allocated for interview, along with
      a key informant clinician and a carer. Interviews were under taken at two time
      points, two years apart. RESULTS: This paper presents the socio-demographic,
      clinical and ethnic characteristics of the patients. CONCLUSIONS: The people with
      psychosis interviewed for the PRiSM Psychosis Study are representative of the
      whole epidemiologically based patient population identified.

PMID- 9926052
TI  - Evolving service interventions in Nunhead and Norwood. PRiSM Psychosis Study. 2.
AB  - BACKGROUND: Service evaluation requires a detailed understanding of the services
      studied. METHOD: Community mental health services evaluated in the PRiSM
      Psychosis Study in south London are described. The intensive sector and standard
      sector services are contrasted. RESULTS: The intensive sector had two teams with
      extended opening hours: a psychiatric acute care and emergency (PACE) team, and a
      psychiatric assertive continuing care (PACT) team focusing on care for people
      with chronic illness. In the standard sector there was a generic community team
      providing office-hour assessments, case management of the severely mentally ill
      and close liaison with in-patient services. The team made use of the local
      psychiatric emergency clinic and of other local resources. The intensive sector
      was characterised by: more admissions to fewer beds, more nonhospital residential
      places, extended hours, on-call rota, wider range of interventions, more medical
      and nursing staff, a lower nursing grade mix and higher staff turnover. The
      standard sector had a less highly resourced generic community psychiatric
      service. CONCLUSIONS: Change in services has been more marked in the intensive
      sector.

PMID- 9926053
TI  - Frequency and predictors of adverse events. PRiSM Psychosis Study. 3.
AB  - BACKGROUND: Community care has been criticised as a hazardous policy associated
      with high rates of adverse events. There is little research evidence as to the
      truth of this claim. METHOD: Best available evidence from public records,
      interviews, case notes, key workers and general practitioners was assembled to
      establish: (a) which of the 514 subjects initially identified as having psychotic
      illnesses had died during an average follow-up of 4.9 years; (b) care currently
      received by all 286 subjects originally selected for interview; and (c) rates of
      major adverse events and of admission for these 286 individuals. RESULTS: Twenty
      eight natural and II unnatural deaths had occurred. Among subjects still living
      at the end of the follow-up, 84% were in contact with specialist mental health
      services and 11% only with primary care services. Rates of serious violence,
      imprisonment and homelessness were relatively low. Forty-one per cent had been
      admitted at least once during a mean follow-up of 3.2 years and 20% at least once
      under the Mental Health Act. After adjustment, there were no significant
      differences between standard and intensive care sectors. CONCLUSIONS: Rates of
      adverse events and 'slipping through the net' are relatively low among
      individuals receiving community-based services, whether intensive or standard
      care.

PMID- 9926054
TI  - Effects of community services on disability and symptoms. PRiSM Psychosis Study.
      4.
AB  - BACKGROUND: Community care for people with psychosis can be provided via several
      different service models. The study compared two models: standard community
      treatment with high patient: staff ratios, and intensive community treatment in
      which there was more of an emphasis on community involvement and lower
      patient:staff ratios. METHOD: All people fulfilling diagnostic criteria for
      psychosis and living in two defined geographical areas in south London were
      identified. These people were provided with either an intensive or standard
      service depending on their address. Their social behaviour and symptoms were
      measured at the beginning of the study and after two years. RESULTS: There is
      little evidence of any effects of the two service models on levels of symptoms.
      However, the standard service did seem to be advantageous in reducing social
      disability for those with medium or low levels of disability. CONCLUSIONS: The
      effect of intensive community services was the opposite to that predicted.
      Despite improvements in outcomes (e.g. hospital admission), there were no
      advantages for this type of service in the measures of disability or symptoms. In
      fact, the standard service was effective in reducing disability, whereas in the
      intensive service there was no change.

PMID- 9926055
TI  - Utilisation and costs of community mental health services. PRiSM Psychosis Study.
      5.
AB  - BACKGROUND: The costs and the effectiveness of mental health services need to be
      evaluated if provision is to be efficient. Service use and costs are described
      for two geographical areas in south London. METHOD: Service use was measured
      comprehensively for clients in both sectors for two six-month time periods using
      the Client Service Receipt Interview. This information was combined with unit
      costs to calculate service costs. The 'hidden' costs of informal care and
      unsupported accommodation were also calculated. RESULTS: At baseline
      significantly more intensive sector clients had in-patient stays but by the
      follow-up this difference had disappeared. There was significantly more use of
      supported accommodation in the intensive sector during both time periods.
      Baseline and follow-up total service costs were significantly higher for the
      intensive sector. Costs were spread disproportionately and a small number of
      services accounted for a large proportion of cost. CONCLUSIONS: While the cost at
      Time 2 was significantly greater in the intensive sector, this was largely due to
      the high use of supported accommodation. There was some convergence in cost
      between the sectors over time.

PMID- 9926056
TI  - Care-giving and the impact on carers of a community mental health service. PRiSM
      Psychosis Study. 6.
AB  - BACKGROUND: We examined: care-giving activities in a population-based sample of
      carers of sufferers from psychotic disorders; putative determinants of care
      giving; and changes in care-giving in an intensive community psychiatric service.
      METHODS: In the PRiSM interview sample 170 people had a carer; 124 were
      interviewed. Care-giving activities, dissatisfaction with these, and carers'
      General Health Questionnaire (GHQ) scores were measured. Patient and illness
      characteristics were examined as predictors of the carer measures. The carer
      measures were reassessed for 62 carers after two years in two service sectors,
      one with an intensive community service, the other with a standard service.
      RESULTS: Overall, 36% of carers were engaged in no, or only occasional care
      giving activities. Fifty per cent expressed no dissatisfaction with their care
      giving role. Patient and illness characteristics predicted care-giving poorly.
      Carers in the intensive community treatment sector did not experience
      significantly different care-giving demands or distress than those in the
      standard sector. CONCLUSIONS: A significant proportion of carers of sufferers
      from psychosis do not engage in common care-giving activities, and are not
      dissatisfied with their role. An intensive community service did not affect the
      impact of the illness on carers.

PMID- 9926057
TI  - Impact of community mental health services on users' social networks. PRiSM
      Psychosis Study. 7.
AB  - BACKGROUND: Social networks are important for people with severe mental illness,
      and services need to assess whether they succeed in improving social contacts.
      METHODS: In a prospective controlled study, social network data were obtained in
      an epidemiologically representative sample of people with psychotic disorders
      both before (Time 1) and two years after (Time 2) the introduction of two
      sectorised community mental health services in south London (one intensive
      service with two specialist teams, one standard service with a generic team).
      RESULTS: There were significant baseline differences between sectors with social
      networks being smaller in the sector later served by the intensive service.
      Social network size increased within the intensive service sector, but not in the
      standard service sector. There was a significant sector effect for the network
      component of relatives (intensive > standard) and in the other ('non friends')
      component (standard > intensive) after adjusting for baseline differences.
      CONCLUSIONS: The findings suggest that the intensive sector community mental
      health service enhanced people's social networks with their relatives, relative
      to the standard service. The reverse is the case for other contacts.

PMID- 9926058
TI  - User perspective on needs and satisfaction with mental health services. PRiSM
      Psychosis Study. 8.
AB  - BACKGROUND: Measurement of the impact of different types of service provision on
      the views of service users is important in planning mental health services.
      METHOD: Needs (met and unmet) and satisfaction with services, were assessed.
      People with psychosis (n = 131) were interviewed before (Time 1) and after (Time
      2) the introduction of two community mental health services in south London. One
      was intensive, with two specialist teams, the other standard. Outcomes were
      compared at Time 2, controlling for the Time 1 values. RESULTS: Overall, 70% of
      needs were met and mean satisfaction was between 'mixed' and 'mainly satisfied'.
      There was evidence for higher met needs in the intensive sector, but no evidence
      for lower unmet needs in the intensive sector or for differences in satisfaction.
      The additional needs met by the intensive service were associated with aspects of
      basic living situation. Satisfaction was negatively correlated with both unmet
      and met needs. CONCLUSIONS: Both services were reasonably successful, with little
      difference from the user perspective. The intensive service provided benefits in
      terms of met needs, but this has to be balanced against a possible increase in
      unmet needs.

PMID- 9926059
TI  - Quality of life outcomes for intensive versus standard community mental health
      services. PRiSM Psychosis Study. 9.
AB  - BACKGROUND: We report the impact on the quality of life (QOL) of people with
      psychosis of an intensive compared with a standard model of community care.
      METHOD: People with psychosis, in two sectors in south London, were interviewed
      with a variety of measures at baseline, and at two-year follow-up (n = 138).
      After baseline, services within one sector were reorganised, and a more intensive
      model of community care was introduced. QOL was measured using the Lancashire
      Quality of Life Profile. RESULTS: The two overall QOL measures, global QOL and
      the average of the domain-specific scores, were remarkably stable over time.
      There was weak evidence for an improvement in living situation domain in the
      intensive sector; this may be accounted for by a large drop in in-patient
      admissions. In both sectors objective QOL was poor, and there was little change
      in any of the objective indicators except in-patient admissions, and a suggestion
      of increased social activity in the intensive sector. CONCLUSIONS: We failed to
      find an effect of intensive community care on QOL in people with psychosis. This
      may indicate an insensitivity to change in QOL measures, or that the intervention
      failed to produce the kind of changes in mental health and functioning which
      would be reflected in improved QOL.

PMID- 9926060
TI  - From efficacy to effectiveness in community mental health services. PRiSM
      Psychosis Study. 10.
AB  - BACKGROUND: The PRiSM Psychosis Study investigated the outcomes of community
      mental health services for epidemiologically representative cases of psychosis in
      London. METHOD: The results presented in the preceding nine papers are
      interpreted. RESULTS: (a) The health and social gains reported in experimental
      studies of community health services are replicable in ordinary clinical
      settings, and are more effective than hospital-oriented services which they
      replace. (b) Dilution does occur--these gains are less pronounced than in
      experimental (efficacy) studies. (c) Both models of community services produced a
      range of improved outcomes. (d) Some limited extra advantages (in terms of met
      needs, improved quality of life, and social networks) were found in the intensive
      sector. (e) There is no consistent evidence that community-oriented services
      (which include in-patient beds) fail service users, their families or the wider
      public. On balance the results weigh slightly in favour of the two-team model
      (for acute and continuing care) in terms of clinical effectiveness, but the
      general model is almost as effective and is less expensive. CONCLUSIONS: The
      evidence supports a community-oriented rather than a hospital-oriented approach
      and there is little difference between the community mental health team models.

PMID- 9926061
TI  - Epidemiology of self-injurious behaviour in adults with learning disabilities.
AB  - BACKGROUND: There have been few epidemiological studies of the disabling and
      poorly understood disorder self-injurious behaviour among adults with learning
      disabilities. METHOD: Interviews were undertaken with the carers of adults known
      to the Leicestershire Learning Disabilities Register (n = 2277). The Disability
      Assessment Schedule was used and information was also collected on demographic
      characteristics, developmental and physical status. RESULTS: Self-injurious
      behaviour was present in 17.4% of the population. In 1.7% self-injurious
      behaviour occurred frequently and was severe. There was no gender difference
      between those with and without self-injurious behaviour. Both the chronological
      age and developmental quotient of individuals with self-injurious behaviour were
      lower than those of individuals without self-injurious behaviour. Autistic
      symptoms were more common among those with self-injurious behaviour. The
      association of self-injurious behaviour with a wide range of other maladaptive
      behaviours was highly significant. Logistic regression analysis retained age,
      developmental quotient, hearing status, immobility and number of autistic
      symptoms as explanatory variables for self-injurious behaviour. CONCLUSIONS: Self
      injurious behaviour is a prevalent and disabling disorder among adults with
      learning disabilities.

PMID- 9926062
TI  - Extent and appropriateness of benzodiazepine use. Results from an elderly urban
      community.
AB  - BACKGROUND: We sought to determine the extent and appropriateness of
      benzodiazepine use in an elderly community, by measuring prevalence and incidence
      of benzodiazepines and examining mental health status as a predictor of
      benzodiazepine use. METHOD: Data were collected from two longitudinal studies of
      people from the same community, sampled in 1982-1983 and again in 1989-1991.
      RESULTS: Benzodiazepine prevalence did not decrease during the period under
      study, but there was a significant reduction in anxiolytic use. Prevalence of
      benzodiazepines in women in twice that in men, and incidence of hypnotics is
      slightly higher in women. Prevalence and incidence of hypnotics are strongly
      associated with increasing age. There were high proportions of long-term users
      (61 and 70%), and continued use was high (52%) among new users. A large
      proportion of benzodiazepine use was by those who were concurrently depressed.
      Similarly, anxiety predicted both current and subsequent use of hypnotics.
      CONCLUSIONS: Many older people still use benzodiazepines, contrary to official
      guidelines with regard to their mental health. Our findings add to the weight of
      opinion that persistent and long-term use should be discouraged.

PMID- 9926063
TI  - Genetic epidemiology of binging and vomiting.

PMID- 9926064
TI  - Genetic epidemiology of binging and vomiting.

PMID- 9926065
TI  - Reserpine exhumed.

PMID- 9926066
TI  - Clozapine-induced extrinsic allergic alveolitis.

PMID- 9926067
TI  - Prolonged bradycardia complicates antidepressive treatment with venlafaxine and
      ECT.

PMID- 9926068
TI  - Doxazosin for reboxetine-induced urinary hesitancy.

PMID- 9926069
TI  - Physical interventions.

PMID- 9926070
TI  - Transcranial magnetic stimulation in depression.

PMID- 9926071
TI  - Using behavioural ecology to understand depression.

PMID- 9926072
TI  - Psychiatric aspects of the Truth and Reconciliation Commission in South Africa.

PMID- 9926073
TI  - L. S. Penrose FRS (1898-1972). Psychiatrist and professor of human genetics.

PMID- 9926074
TI  - Suicide and recency of health care contacts. A systematic review.
AB  - BACKGROUND: Many countries have set targets for suicide reduction, and suggested
      that mental health care providers and general practitioners have a key role to
      play. METHOD: A systematic review of the literature. RESULTS: Among those in the
      general population who commit suicide, up to 41% may have contact with
      psychiatric inpatient care in the year prior to death and up to 9% may commit
      suicide within one day of discharge. The corresponding figures are 11 and 4% for
      community-based psychiatric care and 83 and 20% for general practitioners.
      CONCLUSIONS: Among those who die by suicide, contact with health services is
      common before death. This is a necessary but not sufficient condition for
      clinicians to intervene. More work is needed to determine whether these people
      show characteristic patterns of care and/or particular risk factors which would
      enable a targeted approach to be developed to assist clinicians in detecting and
      managing high-risk patients.

PMID- 9926075
TI  - Incidence, risk and prognosis of acute and chronic fatigue syndromes and
      psychiatric disorders after glandular fever.
AB  - BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome
      (CFS) and depressive illness is uncertain. METHOD: A prospective cohort study of
      250 primary care patients, presenting with glandular fever or an ordinary upper
      respiratory tract infection (URTI). RESULTS: The incidence of an acute fatigue
      syndrome was 47% at onset, after glandular fever, compared with 20% with an
      ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome
      lasted a median (interquartile range) of eight weeks (4-16) after glandular
      fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22%
      six months after glandular fever, compared with 0-6% following an ordinary URTI,
      with relative risks of 2.7-5.1. The most conservative measure of the incidence of
      CFS was 9% after glandular fever, compared with no cases after an URTI. A
      conservative estimate is that glandular fever accounts for 3113 (95% CI 1698
      4528) new cases of CFS per annum in England and Wales. New episodes of major
      depressive disorder were triggered by infection, especially the Epstein-Barr
      virus, but lasted a median of only three weeks. No psychiatric disorder was
      significantly more prevalent six months after onset than before. CONCLUSIONS:
      Glandular fever is a significant risk factor for both acute and chronic fatigue
      syndromes. Transient new major depressive disorders occur close to onset, but are
      not related to any particular infection if they last more than a month.

PMID- 9926076
TI  - Dose-effect relationships of trauma to symptoms of depression and post-traumatic
      stress disorder among Cambodian survivors of mass violence.
AB  - BACKGROUND: The dose-effect relationships of cumulative trauma to the psychiatric
      symptoms of major depression and post-traumatic stress disorder (PTSD) in a
      community study of Cambodian survivors of mass violence were evaluated. METHOD:
      In 1990, a survey of 1000 households was conducted in a Thai refugee camp (Site
      2) using a multi-stage random sampling design. Trauma history and psychiatric
      symptoms were assessed for two time periods. Analysis used linear dose-response
      regression modelling. RESULTS: 993 Cambodian adults reported a mean of 14 Pol Pot
      era trauma events and 1.3 trauma events during the past year. Symptom categories
      of depression, PTSD, dissociative and culturally dependent symptoms exhibited
      strong dose-effect responses with the exception of avoidance. All symptom
      categories, except avoidant symptoms, were highly correlated. CONCLUSIONS:
      Cumulative trauma continued to affect psychiatric symptom levels a decade after
      the original trauma events. The diagnostic validity of PTSD criteria, with the
      notable exception of avoidance, was supported. Inclusion of dissociative and
      culturally dependent symptoms increased the cultural sensitivity of PTSD.

PMID- 9926077
TI  - Social roles and gender difference in the prevalence of common mental disorders.
AB  - BACKGROUND: It is not known why the most common mental disorders, anxiety and
      depression, are more prevalent among women then men. The aim was to test the
      hypothesis that this gender difference could be explained by differences between
      men and women in social role occupancy, after adjusting for age and socio
      economic status. METHOD: A cross-sectional survey of 8979 adults aged 16-74 years
      living in private households in England, Wales and Scotland was carried out.
      Prevalence of common mental disorders was assessed using the General Health
      Questionnaire. RESULTS: The gender difference in the prevalence of the common
      mental disorders (unlike social role occupancy) did not vary with age to a
      statistically significant degree (unadjusted odds ratio 1.35, 95% CI 1.23-1.48)
      (P < 0.0001). Although those of either gender occupying the fewest, and women
      occupying the most social roles (after adjusting for age) had the highest
      prevalence of common mental disorders, neither number of social roles, occupancy
      of traditional 'female' caring and domestic roles, nor socio-economic status
      explained the gender difference in these conditions (adjusted OR 1.26, 95% CI
      1.14-1.41) (P < 0.001). CONCLUSIONS: The gender difference in the prevalence of
      the common mental disorders is not explained by differences between men and women
      in the number or type of social roles occupied.

PMID- 9926078
TI  - Age at onset and outcome in schizophrenia are related to the degree of familial
      loading.
AB  - BACKGROUND: Recent research suggests that high familial loading is associated
      with early onset of schizophrenia. Results concerning outcome have been
      controversial. METHOD: We assessed the relationship between familial loading, age
      at onset and outcome in all Finnish patients with schizophrenia born between 1950
      and 1969. Patients and their first-degree relatives were identified using
      nationwide registers. Familial loading scores were calculated for schizophrenia
      and for combined psychotic disorders, and patients were accordingly classified
      into three groups: high (n = 761), intermediate (n = 14,247), and low familial
      loading (n = 725). Linear mixed models and the Cox proportional hazard model were
      used in the analyses. RESULTS: Onset was earliest, hospitalisation longest and
      risk of retirement in receipt of a disability pension highest in the group with
      high familial loading, with opposite extremes found in the group with low
      familial loading. CONCLUSIONS: High familial loading for schizophrenia is
      associated with early onset and poor outcome of schizophrenia.

PMID- 9926080
TI  - Psychiatric disorders in adolescents in primary care.
AB  - BACKGROUND: Little is known about psychiatric disorders in adolescents who attend
      primary care. METHOD: Prospective study of 13- to 16-year-olds consecutively
      attending general practice. Information was obtained from adolescents, parents
      and general practitioners, using questionnaires and research interviews. RESULTS:
      136/200 (68%) of adolescent attenders took part. Two per cent presented with
      psychiatric complaints. From research interviews with adolescents, psychiatric
      disorder in the previous year was found in 38%, with moderate impairment of
      functioning in over half (according to Children's Global Assessment Scale
      scores). Most disorders (42/50, 84%) were emotional ('internalising') disorders.
      Psychiatric disorders were significantly associated with high levels and
      intensity of physical symptoms and with increased health risks. General
      practitioner assessment of psychiatric disorders was low on sensitivity (20.8%)
      but high on specificity (90.7%). Doctors identified most severely affected
      adolescents. CONCLUSIONS: Depressive and anxiety disorders are common among
      adolescent general practice attenders and linked to increased physical symptoms;
      general practitioner recognition is limited.

PMID- 9926079
TI  - Onset and recovery from panic disorder in the Baltimore Epidemiologic Catchment
      Area follow-up.
AB  - BACKGROUND: The objective is to estimate parameters of the natural history of
      panic disorder, including its prodrome, incidence, recovery and recurrence.
      METHOD: In 1981 the Baltimore Epidemiologic Catchment Area Study interviewed 3481
      individuals probabilistically selected from the household population. During 1993
      1996, 1920 of these individuals (73% of survivors) were interviewed again.
      Baseline and follow-up interviews included the National Institute of Mental
      Health Diagnostic Interview Schedule. During the follow-up, a subsample was
      assessed by psychiatrists using the World Health Organization Schedules for
      Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: There were 35 new cases
      of panic disorder in 24,475 person years of exposure, yielding an annual
      incidence of 1.43 per 1000 per year. Data from the SCAN assessments suggest the
      incidence estimate is conservative. Incidence is greater in females and declines
      with age. About one-third of the new cases arise without agoraphobia, but about
      half have anxiety of some sort present for many years prior to meeting criteria
      for diagnosis. People with agoraphobia have less intense onsets but slower
      recoveries than those without agoraphobia. CONCLUSIONS: Panic is heterogeneous in
      its pattern of onset and recovery. Some of the heterogeneity is associated with
      the presence of other anxiety over a long period of the life.

PMID- 9926081
TI  - Chronic mania. Family history, prior course, clinical picture and social
      consequences.
AB  - BACKGROUND: Mania with chronic course has been overlooked in the recent
      literature. Our aim was clinically to characterise and validate this form of
      mania. METHOD: We evaluated 155 people with DSM-III-R mania and assessed their
      family history, temperament, symptomatology and course. We used a semi-structured
      interview for mood disorders, as well as the Comprehensive Psychopathological
      Rating Scale and the Scale for the Assessment of Positive Symptoms. RESULTS:
      Twenty (13%) had a chronic course arising from a background of hyperthymic
      temperament and recurrent mania, with a deteriorative pattern. Clinically, they
      were characterised by a significantly high rate of almost constant euphoria,
      grandiose delusions and related delusions, but had relatively low rates of sleep
      disturbance, psychomotor agitation and hypersexuality. CONCLUSION: Even with
      current therapies a significant number of people with bipolar disorders have a
      deteriorative outcome associated with the gradual disappearance of acute mania
      with an increase in megalomanic delusions, alienation from loved ones and
      decreased likelihood of medical and psychiatric care.

PMID- 9926082
TI  - Changes in public attitudes to depression during the Defeat Depression Campaign.
AB  - BACKGROUND: Aims of the Defeat Depression Campaign between 1991 and 1996 included
      the reduction of stigma associated with depression, education of the public about
      the disorder and its treatment and encouragement of earlier treatment-seeking.
      Newspaper and magazine articles, radio and television programmes and other media
      activities were employed. METHOD: Surveys of public attitudes were conducted by
      MORI in late 1991, early 1995 and mid-1997. Each covered approximately 2000
      subjects, sampled to be representative of the population of Great Britain.
      Structured interviews covered views on depression, treatment and general
      practitioners (GPs). RESULTS: There were significant positive changes regarding
      attitudes to depression, reported experience of it, attitudes to antidepressants,
      and less consistently, to treatment from GPs. Changes were of the order of 5-10%.
      Throughout, attitudes to depression and to treatment by counselling were very
      favourable, whereas antidepressants were regarded as addictive and less
      effective. CONCLUSIONS: Positive attitude change was achieved during the
      Campaign, although there is still room for improvement in some aspects.

PMID- 9926083
TI  - Genetic and non-genetic subtypes of major depressive disorder.
AB  - BACKGROUND: We aimed to examine the hypotheses that major depression is
      aetiologically heterogeneous consisting of a mixture of 'genetic' and 'non
      genetic' forms or, alternatively, a mixture of one form that is 'pure' depression
      and another that has a familial relationship with alcohol dependency or other
      disorders. METHOD: One hundred and eleven twin pairs (44 monozygotic, 67
      dizygotic) where the proband had received treatment for DSM-IV major depression
      were ascertained via a hospital register. Family history information on parents
      and siblings was obtained from the proband, co-twin or both. Diagnoses on parents
      and siblings were made blind to twin zygosity or concordance and compared in the
      relatives of concordant versus discordant twins. RESULTS: The lifetime prevalence
      and age-corrected risk of depression were no different in the relatives of
      concordant and discordant twin pairs. There was a marginally significant increase
      in the rate of alcohol abuse or dependence among the relatives of concordant
      twins but no difference between concordant and discordant pairs in respect of
      other axis I diagnosis among family members. CONCLUSIONS: The results argue
      against genetic heterogeneity and suggest that major depression cannot usefully
      be divided into genetic and non-genetic forms or into 'pure' depression and
      depression associated with other disorders such as alcohol dependency.

PMID- 9926084
TI  - Family history as a predictor of poor long-term outcome in depression.
AB  - BACKGROUND: We investigated whether family history had prognostic significance in
      depression in a study which addressed some of the methodological shortcomings of
      previous studies. METHOD: We collected family history data on a consecutive
      series of 89 patients admitted with RDC major depression, blind to the outcome of
      the proband. This comprised 116, 283 and 120 first-degree relatives examined with
      the SADS-L, FH-RDC and case note data, respectively. The outcome of 74 of these
      probands (83%), previously categorised into four operationally defined groups,
      was then examined. RESULTS: A positive family history of severe psychiatric
      illness (i.e. a relative with a history of either a psychosis, hospitalised
      depression or suicide) was associated with poor outcome in the proband. This
      association persisted after controlling for variable family size, age structure
      and gender. As family history was correlated with neither Kendell's
      neurotic/psychotic index nor the proband's neuroticism score, an individual with
      high scores an all three would have a greatly increased chance of having a poor
      outcome. CONCLUSIONS: A family history of severe psychiatric illness in a first
      degree relative may be useful as one of the vulnerability factors for predicting
      poor long-term outcome in depression.

PMID- 9926085
TI  - Suicide attempts preceding completed suicide.
AB  - BACKGROUND: This study investigated three questions with major implications for
      suicide prevention: the sensitivity of the history of previous suicide attempt(s)
      as an indicator of suicide risk, the time interval from a preceding suicide
      attempt to the fatal one, and switching of suicide methods by those eventually
      completing suicide. METHOD: The lifetime history of suicide attempts and the
      methods the victims (n = 1397) used were examined in a nationwide psychological
      autopsy study comprising all suicides in Finland within a 12-month research
      period in 1987-1988. RESULTS: Overall, 56% of suicide victims were found to have
      died at their first suicide attempt, more males (62%) than females (38%). In 19%
      of males and 39% of females the victim had made a non-fatal attempt during the
      final year. Of the victims with previous attempts, 82% had used at least two
      different methods in their suicide attempts (the fatal included). CONCLUSIONS:
      Most male and a substantial proportion of female suicides die in their first
      suicide attempt, a fact that necessitates early recognition of suicide risk,
      particularly among males. Recognition of periods of high suicide risk on the
      grounds of recent non-fatal suicide attempts is likely to be important for
      suicide prevention among females. Subjects completing suicide commonly switch
      from one suicide method to another, a finding that weakens but does not negate
      the credibility of restrictions on the availability of lethal methods as a
      preventive measure.

PMID- 9926086
TI  - Premorbid adjustment and schizophrenia.

PMID- 9926087
TI  - Pindolol augmentation of antidepressant therapy.

PMID- 9926088
TI  - Neurosurgery for obsessive-compulsive disorder.

PMID- 9926089
TI  - Loss of consciousness and post-traumatic stress disorder.

PMID- 9926091
TI  - Meditation and psychotherapy.

PMID- 9926090
TI  - Recovered memories of abuse and dissociative identity disorder.

PMID- 9926092
TI  - Youth suicide trends in the Republic of Ireland.

PMID- 9926093
TI  - Limitations of the symptom-oriented approach to psychiatric research.
AB  - BACKGROUND: We critically reviewed the arguments of the symptom-oriented
      researchers who propose to replace syndromes and diagnostic categories with
      symptoms as units of analysis in psychiatric research. METHOD: Three central
      arguments were examined: (a) current diagnostic categories lack reliability and
      validity; (b) using diagnostic categories leads to misclassification and
      confounding; and (c) symptom-oriented theories are clearer, easier to test, and
      more likely to lead to an explanation of psychopathology. These arguments are
      based on three assumptions respectively: (a) symptoms have higher reliability and
      validity; (b) underlying pathological processes are symptom-specific; and (c)
      elucidation of the process of symptom development will lead to (and must precede)
      the discovery of the causes of syndromes. RESULTS: We found little evidence
      supporting these assumptions and arguments based on them. CONCLUSION: There are
      no clear advantages in replacing syndromes with symptoms as units of analysis for
      psychiatric research.

PMID- 9926094
TI  - Pindolol augmentation of antidepressant therapy.
AB  - BACKGROUND: Antidepressant therapy is not always effective and is slow to take
      effect. In theory, these shortfalls may be caused by induction of neuronal
      negative feedback via pre-synaptic 5-HTIA receptors. Pindolol, an antagonist at
      somatodentritic pre-synaptic 5-HTIA receptors has been investigated as a
      potential accelerator and augmentor of antidepressant response. METHOD: A Medline
      search was conducted in November 1997. RESULTS: Six open-label studies and six
      controlled studies were identified for review. CONCLUSIONS: Open-label studies
      strongly suggest that pindolol may accelerate and augment antidepressant
      response, but controlled studies do not wholly support these findings: only three
      of six studies clearly demonstrate benefit. Larger, well-designed, controlled
      trials are needed to determine definitively the effectiveness of pindolol in this
      context.

PMID- 9926095
TI  - Suicide and other causes of mortality after post-partum psychiatric admission.
AB  - BACKGROUND: The risk of suicide in postnatal women is low and those suicides that
      occur appear to be associated with severe psychiatric illness. No previous study
      has specifically studied the risk of suicide following post-partum psychiatric
      disorder. METHOD: We calculated standardised mortality ratios (SMRs) for suicide,
      unnatural deaths and deaths from natural causes for women admitted to psychiatric
      hospital in the first year after childbirth, using computerised cross-linkages
      between the Danish Psychiatric Case Register and the Danish registers of birth
      and causes of death for 1973-1993. RESULTS: During the study period 1567 women
      were admitted to psychiatric hospital of whom 107 (6.8%) died. The SMRs (compared
      with 100) were 1719 (95% CI1284-2254) for suicide, 1329 (95% CI1038-1676) for all
      unnatural causes and 238 (95% CI167-329) for natural causes. Suicides and deaths
      from all unnatural causes were most likely to occur in the first year after
      childbirth, the SMR for suicide within one year being 7216 (95% CI 3945-12 108).
      CONCLUSIONS: Although postnatal women as a whole appear to have a low rate of
      suicide, severe post-partum psychiatric disorder is associated with a high rate
      of deaths from natural and unnatural causes, particularly suicide. The risk is
      especially high in the first postnatal year, when the suicide risk is increased
      70-fold. Close clinical supervision at this time is indicated.

PMID- 9926096
TI  - Specific fears and phobias. Epidemiology and classification.
AB  - BACKGROUND: Data on eight specific fears representing DSM-III-R simple phobia
      were analysed to evaluate: (a) their prevalence and (b) the validity of subtypes
      of specific phobia defined by DSM-IV. METHOD: A modified version of the Composite
      International Diagnostic Interview was administered to a probability sample of
      8098 community respondents. Correlates of responses to questions concerning these
      fears were analysed. RESULTS: The most prevalent specific fears were of animals
      among women, and of heights among men. Slight evidence was found for specific
      phobia subtypes. Number of fears, independent of type, powerfully predicted
      impairment, comorbidity, illness course, demographic features, and family
      psychopathology. CONCLUSION: Number of specific fears may mark a general
      predisposition to psychopathology. More detailed information is needed to resolve
      the question of specific phobia subtypes.

PMID- 9926097
TI  - Two psychological treatments for hypochondriasis. A randomised controlled trial.
AB  - BACKGROUND: Hypochondriasis is generally considered difficult to manage. This
      study aimed to assess the effectiveness of cognitive therapy and to compare it
      with an equally credible, alternative treatment. METHOD: Forty-eight patients
      with hypochondriasis were initially randomly assigned to either cognitive
      therapy, behavioural stress management or a no treatment waiting list control
      group. At the end of the waiting period, patients in the control group were
      randomly assigned to one of the two treatments. Assessments were at pre-, mid-
      and post-treatment or waiting list and at three-, six- and 12-month post
      treatment follow-up. RESULTS: Comparisons with the waiting list group showed both
      treatments were effective. Comparisons between the treatments showed that
      cognitive therapy was more effective than behavioural stress management on
      measures of hypochondriasis, but not general mood disturbance at mid-treatment
      and at post-treatment. One year after treatment patients who had received either
      treatment remained significantly better than before treatment, and on almost all
      measures the two therapies did not differ from each other. CONCLUSIONS: Cognitive
      therapy is a specific treatment for hypochondriasis. Behavioural stress
      management is also effective but its specificity remains to be demonstrated.

PMID- 9926098
TI  - Long-term course of acute brief psychosis in a developing country setting.
AB  - BACKGROUND: This study in North India compared acute brief psychosis--defined by
      acute onset, brief duration and no early relapse--with other remitting psychoses,
      over a 12-year course and outcome. METHOD: In a cohort of incident psychoses, we
      identified 20 cases of acute brief psychosis and a comparison group of 43 other
      remitting psychoses based on two-year follow-up. Seventeen people (85%) in the
      acute brief psychosis group and 36 (84%) in the comparison group were reassessed
      at five, seven and 12 years after onset, and were rediagnosed using ICD-10
      criteria. RESULTS: At 12-year follow-up, the proportion with remaining signs of
      illness was 6% (n = 1) for acute brief psychosis versus 50% (n = 18) for the
      comparison group (P = 0.002). Using ICD-10 criteria, the majority in both groups
      were diagnosed as having schizophrenia. CONCLUSIONS: Acute brief psychosis has a
      distinctive and benign long-term course when compared with other remitting
      psychoses. This finding supports the ICD-10 concept of a separable group of acute
      and transient psychotic disorders. To effectively separate this group, however,
      the ICD-10 criteria need modification.

PMID- 9926099
TI  - Pathophysiology of 'positive' thought disorder in schizophrenia.
AB  - BACKGROUND: Formal thought disorder is a characteristic feature of psychosis, but
      little is known of its pathophysiology. We have investigated this in
      schizophrenia using positron emission tomography (PET). METHOD: Regional cerebral
      blood flow was measured using H2(15)O and PET while six people with schizophrenia
      were describing a series of 12 ambiguous pictures which elicited different
      degrees of thought-disordered speech. In a within-subject design, the severity of
      'positive' thought disorder was correlated with cerebral blood flow across the 12
      scans in each subject. RESULTS: Verbal disorganisation (positive thought
      disorder) was inversely correlated with activity in the inferior frontal,
      cingulate and left superior temporal cortex, and positively correlated with
      activity in the parahippocampal/anterior fusiform region bilaterally, and in the
      body of the right caudate (P < 0.001). The total amount of speech produced
      (independent of thought disorder) was positively correlated with activity in the
      left inferior frontal and left superior temporal cortex. CONCLUSIONS: The
      severity of positive thought disorder was inversely correlated with activity in
      areas implicated in the regulation and monitoring of speech production. Reduced
      activity in these regions may contribute to the articulation of the linguistic
      anomalies that characterise positive thought disorder. The positive correlations
      between positive thought disorder and parahippocampal/anterior fusiform activity
      may reflect this region's role in the processing of linguistic anomalies.

PMID- 9926100
TI  - 5-HT2A receptor blockade in patients with schizophrenia treated with risperidone
      or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150.
AB  - BACKGROUND: 5-HT2A receptor antagonism may be crucial to the action of atypical
      antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical
      efficacy and protection from extrapyramidal side-effects. METHOD: We developed a
      SPET imaging protocol for assessing 5-HT2A receptor binding using the selective
      ligand 123I-5-I-R91150. Six healthy volunteers, five clozapine- and five
      risperidone-treated subjects with DSM-IV schizophrenia were studied. Multi-slice
      SPET was performed on each subject. RESULTS: Cortex:cerebellum ratios were
      significantly lower in both clozapine- and risperidone-treated subjects compared
      with the healthy volunteers in all cortical regions. There was no difference in
      occupancy between the two drug-treated groups. No correlation was found between
      the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor
      binding indices in the drug-treated groups. CONCLUSIONS: Clozapine and
      risperidone potently block 5-HT2A receptors in vivo. The lack of relationship
      between receptor binding indices and change in GAS suggests that 5-HT2A receptor
      blockade may be unrelated to clinical improvement. Future studies will
      substantiate this finding by studying 5-HT2A receptor binding in large groups of
      patients treated with both typical and novel atypical antipsychotics.

PMID- 9926102
TI  - Culturally sensitive validation of screening questionnaires for depression in
      older African-Caribbean people living in south London.
AB  - BACKGROUND: We tested the validity of two screens for depression in older African
      Caribbean adults, the 15-item Geriatric Depression Scale (GDS) and a new
      Caribbean Culture-Specific Screen for emotional distress (CCSS). Two independent
      criteria were used for validity: (a) a psychiatric diagnosis derived from GMS
      AGECAT, and (b) a culturally sensitive assessment of mental disorder, derived
      from a tool developed with local African-Caribbean religious healers. METHOD: One
      hundred and sixty-four consecutive African-Caribbean primary care users, aged 60
      years or older, were screened with the GDS and the CCSS. Diagnostic interviews
      were carried out on 80% of high scorers and 20% of low scorers. RESULTS: The
      number of cases detected by the two separate diagnostic approaches was similar.
      However, the agreement between who was and who was not a case was only modest. At
      a cut-off of > or = 5, the GDS was an adequate case detector for psychiatric
      depression, and, at a cut-off of > or = 4, for 'depressed/lost spirit', as
      defined by culture-specific criteria. It performed as well as the new CCSS.
      CONCLUSIONS: At a cut-off of > or = 4 the 15-item GDS can be recommended as a
      case detector for significant forms of depression in older African-Caribbean
      people living in south London.

PMID- 9926101
TI  - Placebo run-in period in studies of depressive disorders. Clinical, heuristic and
      research implications.
AB  - BACKGROUND: In spite of the virtually ubiquitous nature of the initial 10-day
      placebo run-in period (IPR) in drug trials, there is little empirical data
      establishing its relevance. METHOD: Data from 593 subjects were examined
      retrospectively to determine whether or not the prognosis of subjects minimally
      improved during the IPR was different to those who were unimproved. The IPR
      period was single-blind and was followed by a six-week double-blind phase in all
      studies. RESULTS: Twenty-six per cent of the subjects were minimally improved and
      74% were unimproved. Approximately 10% of the subjects who were much improved
      were not followed systematically. Across a range of diagnosis, severity and
      chronicity subjects minimally improved (versus unimproved) after IPR had a more
      favourable prognosis whether assigned to drug or placebo. CONCLUSIONS: Change
      during IPR appears to be a meaningful predictor. Stratification should be
      considered in future antidepressant studies.

PMID- 9926103
TI  - Temporal relationships between physical symptoms and psychiatric disorder.
      Results from a national birth cohort.
AB  - BACKGROUND: Physical symptoms and psychiatric disorder are associated. We aimed
      to investigate which comes first. METHODS: Data from the Medical Research Council
      National Survey of Health and Development, a population-based birth cohort study
      were used at two time points: 36 and 43 years. Six physical symptoms were
      reported at both time points. The Present State Examination and Psychiatric
      Symptom Frequency interviews were administered at 36 and 43 years respectively.
      Odds ratios corrected for a variety of confounders were used to describe the
      associations between physical symptoms and psychiatric disorder across these two
      time points. RESULTS: Psychiatric disorder increased the odds of reporting
      symptoms 3-7-fold. The relationship strengthened when the outcome was defined as
      suffering from multiple symptoms. Population attributable risk of psychiatric
      disorder and subsyndromal disorder in causing multiple somatic symptoms was
      40.3%. Prospectively, psychiatric disorder at 36 years was a predictor for five
      of the six physical symptoms. Three physical symptoms at 36 years predicted new
      onset of psychiatric symptoms at 43 years. CONCLUSIONS: Psychiatric disorder is
      strongly related to physical symptoms. The direction of causality may operate in
      both directions. Assuming a causal relationship, psychiatric disorder (including
      sub-threshold disorders) could account for at most 40% of cases of multiple
      physical symptoms.

PMID- 9926104
TI  - Somatisation disorder in primary care.
AB  - BACKGROUND: Somatisation is a common and frustrating clinical problem in primary
      care. METHOD: Using structural diagnoses and functional measures, we examined the
      prevalence and associated features of somatisation disorder defined by three
      current nosologies and an abridged construct in subjects using primary care
      services. RESULTS: Somatisation disorder, diagnosed according to the standard
      criteria, was found to have a very low prevalence (range 0.06-0.5%), while more
      than one-fifth of the sample (22%) met the criteria for the abridged diagnosis.
      There was poor agreement between succeeding versions of the DSM system for
      identifying cases of somatisation disorder, each system ending up with rather
      disparate sets of individuals as well as variable levels of psychopathology and
      disability. CONCLUSIONS: According to these data, standard somatisation disorder
      diagnoses add little to the prediction of disability/psychopathology beyond the
      contributions of an abridged construct of somatisation.

PMID- 9926105
TI  - Does electroconvulsive therapy lead to changes in cerebral structure.

PMID- 9926106
TI  - Risperidone-induced rabbit syndrome.

PMID- 9926107
TI  - Jet lag and relapse of schizoaffective psychosis despite maintenance clozapine
      treatment.

PMID- 9926108
TI  - Testicular pain and swelling on withdrawal of imipramine.

PMID- 9926109
TI  - Adults with Williams syndrome.

PMID- 9926110
TI  - White matter abnormalities and memory in Alzheimer's disease.

PMID- 9926111
TI  - Prevalence of seasonal affective disorder.

PMID- 9926112
TI  - Sudden death in psychiatric patients.

PMID- 9926113
TI  - Analysis of drop-out data in treatment trials.

PMID- 9926114
TI  - Validity of the Chinese version of the Edinburgh Postnatal Depression Scale.

PMID- 9926115
TI  - Compliance, adherence, concordance...

PMID- 9926116
TI  - Patients in cyberspace: information or confusion?

PMID- 9926117
TI  - Isolated diastolic heart failure--what is it?
AB  - Epidemiological evidence suggests that 20 to 40% of all patients with heart
      failure have normal systolic function. Isolated diastolic dysfunction may be the
      principle pathophysiological mechanism in these patients. The diagnosis of
      isolated diastolic heart failure is problematic and not merely based on
      demonstrating normal systolic function. The prognosis in isolated diastolic heart
      failure is more favourable than in systolic heart failure. At the present time,
      there is no licensed treatment for isolated diastolic heart failure and treatment
      is largely empirical.

PMID- 9926118
TI  - Patterns of injury associated with automobile airbag use.
AB  - The wide use of automobile airbags has undoubtedly reduced the mortality and the
      incidence of serious injuries from motor vehicle accidents. However, automobile
      airbags appear to be associated with a variety of injuries including fatal
      injuries, ocular injuries, upper limb and chest injuries. Further improvements in
      airbag design together with education of the general public in their use should
      help reduce airbag-related injuries.

PMID- 9926120
TI  - Intracoronary ultrasound.
AB  - Although contrast angiography is important in the diagnosis and treatment of
      atherosclerotic disease, it does have limitations. Intracoronary ultrasound more
      accurately assesses the amount of atherosclerosis and has given us new insights
      into the pathophysiology of coronary plaque accumulation and remodelling. It also
      allows the monitoring of therapeutic intervention. Intracoronary ultrasound is a
      new gold standard. It does not obviate the need for angiography but provides
      complementary information that enables us to perform optimal interventional
      procedures.

PMID- 9926119
TI  - Abdominal tuberculosis.
AB  - Tuberculosis has staged a global comeback and forms a dangerous combination with
      AIDS. The abdomen is one of the common sites of extrapulmonary involvement.
      Patients with abdominal tuberculosis have a wide range and spectrum of symptoms
      and signs; the disease is therefore a great mimic. Diagnosis, mainly radiological
      and supported by endoscopy, is difficult to make and laparotomy is required in a
      large number of patient. Management involves judicious combination of
      antitubercular therapy and surgery which may be required to treat complications
      such as intestinal obstruction and perforation. The disease, though potentially
      curable, carries a significant morbidity and mortality.

PMID- 9926121
TI  - Smoking and pursuit of thinness in schoolgirls in London and Ottawa.
AB  - It has been proposed that teenage girls often smoke cigarettes to protect
      themselves from the impulse to binge eat, with its feared weight-gain
      consequences, particularly when other measures such as greater dietary restraint
      have failed. The present study looked at the relationship between body mass index
      and standardised questionnaire responses concerning smoking, alcohol consumption,
      moods, weight changes, attitudes to body weight and shape, dietary patterns and
      menstruation in 1936 British (London) and 832 Canadian (Ottawa) schoolgirls. Data
      analysis revealed links between cigarette smoking and body weight/shape concerns,
      and awareness by subjects of these links; there was also a tendency for smokers
      in these two populations to be overweight but not grossly obese. Smoking was also
      related at all ages to being postmenarchal. The London population in particular
      revealed an association between smoking and a weight loss of 7 kg or more at some
      stage since puberty. Smoking was also linked, in a minority, with regular
      vomiting undertaken as a further defence against weight gain when overeating had
      occurred. These associations existed alongside the major and predictable
      association found between alcohol consumption and smoking. Similarities between
      the British and Canadian schoolgirls were striking in respect of rank order of
      reasons given for smoking and consequences of giving it up. Since smoking amongst
      older women is reportedly associated with below-average body weight it may indeed
      be effective in helping to curb weight gain. Our study provided little evidence
      of association between smoking and generalised anxiety or social anxiety (in
      either population), or depression (in the British cohort). We suggest that any
      preventive psychological approach to teenage female smoking should include
      attention to weight gain anxiety and consequent pursuit of thinness.

PMID- 9926122
TI  - Elevated glycated haemoglobin in non-diabetic patients is associated with an
      increased mortality in myocardial infarction.
AB  - Diabetes is associated with increased mortality following acute myocardial
      infarction compared to the general population. Elevated glycated haemoglobin
      (HbA1c) in diabetic patients is also associated with increased mortality
      following acute myocardial infarction, while mild elevation in HbA1c are
      associated with impaired glucose tolerance. The aim of this study was to
      determine the influence of HbA1c on outcome of acute myocardial infarction in 253
      non-diabetic patients, 46 of whom died in one year. In univariate analysis, risk
      factors for death included smoking, glucose, cholesterol and HbA1c. In logistic
      regression analysis HbA1c was an independent risk factor for death. Over one
      third of the fatality group had an HbA1c in the highest quartile, compared to one
      fifth of the surviving group (p = 0.02). Elevated HbA1c is a risk marker for
      short-term mortality following acute myocardial infarction in non-diabetic
      subjects.

PMID- 9926123
TI  - Ursodeoxycholic acid therapy for primary biliary cirrhosis. A 10-year British
      single-centre population-based audit of efficacy and survival.
AB  - The effect of ursodeoxycholic acid treatment on survival in primary biliary
      cirrhosis was studied in 40 patients with symptomatic disease. Two patients
      developed early exacerbation of symptoms and stopped therapy in days; they are
      both alive 4 and 4 1/2 years later. The other 38 patients have continued on
      treatment for up to 10 years. Results were compared with 12 other similar cases
      previously seen but not given specific therapy. Kaplan-Meier analysis showed that
      ursodeoxycholic acid treatment was associated with better survival (p < 0.05)
      after the first two years of therapy. Predictors of favourable outcome included
      histological stage I disease. In 26 patients with primary biliary cirrhosis stage
      II, III or IV, therapy showed a trend to improved survival, but this was still
      significantly worse than the general population. Prognosis was not different
      between these different advanced stages. Symptoms improved in 28 out of 40
      patients on ursodeoxycholic acid, but 50% had a recurrence by two years.

PMID- 9926124
TI  - Intravascular monitoring of successful reperfusion following rescue angioplasty.

PMID- 9926125
TI  - Cytomegalovirus infection associated with ulcerative colitis in immunocompetent
      individuals.
AB  - Gastrointestinal infection with cytomegalovirus (CMV) is usually found in
      immunocompromised patients and rarely affects immunocompetent subjects. We
      describe two immunocompetent patients who had primary CMV infection, and in both
      the disease was associated with ulcerative colitis. Both patients recovered from
      the CMV infection spontaneously.

PMID- 9926126
TI  - Familial cavernous angiomas masquerading as multiple sclerosis.
AB  - We report here two cases of cavernous angioma, in the proband and her father,
      with quite different clinical presentations. The proband presented with a
      brainstem syndrome, mimicking multiple sclerosis, while the father had a history
      of mild epilepsy. Both patients were managed conservatively. The cases also
      demonstrate the utility of magnetic resonance imaging in the diagnosis of
      cavernous angioma.

PMID- 9926127
TI  - Plasma expanders used to treat or prevent hypotension can themselves cause
      hypotension.

PMID- 9926128
TI  - Diabetic ketoacidosis and clozapine.

PMID- 9926129
TI  - Multiple gastrointestinal complications in Marfan syndrome.

PMID- 9926131
TI  - An unconscious patient with an electrocardiogram mimicking an acute myocardial
      infarct.

PMID- 9926130
TI  - Recurrent infections and multiple bone fractures in a 4-year-old child.

PMID- 9926132
TI  - An abdominal mass following a road traffic accident.

PMID- 9926134
TI  - A spontaneous discharging wound on the abdominal wall.

PMID- 9926133
TI  - A hypogammaglobulinaemic man with respiratory failure.

PMID- 9926135
TI  - A neurosurgically reversible cause of respiratory dysfunction in rheumatoid
      arthritis.

PMID- 9926136
TI  - Hepatitis B and C virus infection in patients with high serum transaminases.

PMID- 9926137
TI  - Are anti-oxidant and anti-inflammatory treatments effective in different
      subgroups of COPD? A hypothesis.
AB  - The treatment of chronic obstructive pulmonary disease (COPD) with inhaled
      corticosteroids or anti-oxidants is still under debate and the identification of
      sub-groups of COPD patients who may benefit from either anti-inflammatory or anti
      oxidant treatment is needed. We re-analysed data from an earlier study of inhaled
      beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to
      determine patient characteristics that predict a favourable inhaled steroid
      treatment effect. A higher bronchodilatory response, a faster decline of FEV1
      prior to the treatment period and a lower Tiffeneau index were significantly
      related to more beneficial treatment effects. Increased smoking tended to be
      related to less steroid treatment benefits, though it was not statistically
      significant. In this paper these findings are presented in light of the available
      literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis
      the hypothesis is presented that anti-oxidant treatment might be relatively more
      effective among those COPD patients who respond less well to inhaled steroids
      (low reversibility and heavy smoking).

PMID- 9926138
TI  - Screening patients in general practice with COPD for long-term domiciliary oxygen
      requirement using pulse oximetry.
AB  - Epidemiological data suggest long-term oxygen therapy (LTOT) delivered by oxygen
      concentrators in patients with severe hypoxic chronic obstructive pulmonary
      disease (COPD) is under-prescribed by General Practitioners (GPs) in England and
      Wales. One reason for this may be the unavailability to GPs of a measure of
      arterial oxygenation needed to fulfil the defined prescription criteria.
      Provision of a non-invasive measure of oxygenation may improve detection of
      hypoxic subjects and increase appropriate prescribing. This study aimed to
      evaluate pulse oximetry in a general practice setting and to screen for severe
      undetected hypoxaemia fulfilling the LTOT prescription criteria in patients with
      COPD. All COPD patients attending surgery in two practices were screened with
      oximeters for hypoxaemia. Those with an oxygen saturation of < or = 92% were
      referred to hospital for formal arterial blood gas analysis and an oxygen
      concentrator assessment. GPs were asked to evaluate their experience in the ease
      of use and application of oximetry. The number of patients receiving oxygen by
      concentrator before the study was compared with the national rate and the number
      after the study with the estimated need suggested by epidemiological studies.
      Over a 12-month period a total of 114 patients were screened in the two practices
      with a combined list size of 15,742. Thirteen patients had saturations of < or =
      92%. Two refused and 11 underwent formal arterial gas analysis. Three had PaO2 <
      7.3 kPa and new prescriptions for oxygen concentrators were made in these
      previously unsuspected severely hypoxaemic subjects as a result. One other
      hypoxaemic subject was referred and found to have another treatable medical
      condition. The initial prevalence of concentrator prescription (0.013% CI 0.003,
      0.047) was similar to the national rate (0.024%) and the prevalence observed
      after screening (0.031%, CI 0.013, 0.073) fell within the lower suggested
      prescription need of previous epidemiological data (0.02-0.10%). All
      practitioners found the oximeters simple to use and helpful in assisting with
      assessment of the severity of their patient's condition. Oximetry provides a
      readily usable non-invasive method of screening and when applied to all COPD
      patients seen in general practice can reveal those fulfilling the criteria for
      long term oxygen who would otherwise not be identified as needing this treatment.

PMID- 9926139
TI  - Pneumothorax in active pulmonary tuberculosis: resurgence of an old complication?
AB  - With the recent resurgence of tuberculosis (TB) in western countries, the
      incidence of complicating secondary pneumothorax has also increased. The work-up
      and management of this complication differs from that in other types of secondary
      spontaneous pneumothorax (SSP). Our objective was to assess clinical features and
      therapeutic modalities of SSP in patients with and without active pulmonary
      tuberculosis (APTB). All patients diagnosed with SSP seen at the Hospital Xeral
      of Vigo from January 1990 to June 1995 were candidates for this study. Full
      clinical, radiological and examinations were performed in all patients. Invasive
      procedures (thoracic catheter aspiration, thoracoscopy and thoracotomy) and mean
      hospital stay were compared in patients with and without APTB. Forty-eight
      patients with SSP were enrolled. Eleven patients (10 males and one female, mean
      age 30 +/- 11 years) had APTB; and 37 patients (31 males and six females, mean
      age 49 +/- 20 years) had conditions other than APTB. Chest pain, cough and fever
      were more frequent in patients with APTB (90% vs 59%; 45% vs 13.5%; 36% vs 5%,
      respectively). Catheter aspiration was successful in three of 10 (30%) of
      patients with APTB and in 15/23 (60.86%) of those without APTB. Catheter
      aspiration time was longer in the former group (25 +/- 22 days vs 13 +/- 11 days,
      P = 0.17). As initial treatment, thoracoscopy was performed in seven of 37
      (18.91%) of those without APTB and in one of 10 (10%) patients with APTB. For
      patients with unsuccessful catheter aspiration, thoracoscopy was performed in
      eight of nine (89%) patients without APTB and in none of the patients with APTB.
      Thoracotomy was performed in only one of nine (11%) without APTB and in four of
      seven (57%) patients with APTB. Patients with APTB had a longer hospitalization
      (41 vs 18 days, P < 0.001). We concluded that SSP and APTB was a frequent
      association in our study. Patients with APTB showed a lesser and slower response
      to catheter aspiration. Despite severe clinical presentation and demand for more
      invasive procedures, patients with APTB showed a favourable response.

PMID- 9926140
TI  - The Darlington and Northallerton Prospective Asthma Study: best function predicts
      mortality during the first 10 years.
AB  - The Darlington/Northallerton prospective study of asthmatics referred to
      secondary care started in 1983, with review and new entry at 5-yr intervals. The
      principal outcome measures are: mortality (presented here), best function and
      therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF)
      reversibility to > or = 200 l min-1 were included. Socio-demographic variables,
      PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF
      were assessed according to protocol. The mortality of the original cohort after
      10 yr was expressed as standardized mortality ratio (SMR) against the local
      population, with history and pulmonary function at entry as explanatory
      variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173
      deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47,
      95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%).
      After allowance for age and sex, there was a consistent inverse relationship
      between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33
      1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was
      eight times greater, and of non-respiratory death three times greater, in the
      lowest compared with the highest quartile of best FVC. There were no interactions
      with smoking, but possible enhancement of the effect in the socially deprived.
      Best FVC was a particularly powerful predictor of mortality in subjects < 65
      years at entry, in whom 64% of the excess deaths occurred. Most of the excess in
      respiratory deaths was not due to acute severe asthma but to the development of
      chronic obstructive pulmonary disease (COPD), as defined functionally,
      irrespective of smoking habit which made no further contribution to mortality.

PMID- 9926141
TI  - Verification of self-reported asthma and allergy in subjects and their family
      members volunteering for gene mapping studies.
AB  - Studies which aim at mapping genes contributing to the development of asthma and
      atopy demand that hundreds of patients and their family members be assessed. In
      Finland, the Social Insurance Institution (SII) grants substantial reimbursement
      for medication to all patients who meet diagnostic criteria of asthma, which
      include a history of asthmatic symptoms and a measured reversibility of bronchial
      obstruction. To recruit a large number of asthma patients efficiently in a short
      period of time, we took advantage of the national reimbursement procedure and
      retrospectively collective data on patients' medical history and lung function
      test results at the time of diagnosis. First, we wanted to investigate if the
      reimbursements could be regarded as objective verification for self-reported
      asthma. Altogether 335 adult self-reported asthma patients were evaluated, 87% of
      them were verified as having chronic asthma. Reimbursement for medication showed
      a sensitivity of 95% and a specificity of 76% for verified asthma. Second, we
      were interested to see if self-reported nasal allergic symptoms or self-reported
      physician diagnosed allergic rhinitis were sensitive and specific measures of
      allergy. The self-reported allergic nasal symptoms had a poor specificity (31% in
      the proband group and 59% in the family members group) when compared to the
      allergy screening test (Phadiatop). The best verification for self-reported
      asthma was achieved by combining the information on self-reported disease,
      granted reimbursement by the SII and the medical records. For allergies, the
      specificity of self-reporting was far too low to be used alone, and a positive
      allergy screening test together with relevant symptoms was chosen as a marker of
      allergy.

PMID- 9926142
TI  - The management of pulmonary tuberculosis in adults notified in Scotland in 1993.
AB  - The management of pulmonary tuberculosis (TB) in Scotland in 1993 was studied by
      asking the physicians responsible for all 321 adult cases of the disease notified
      that year to complete a standardized questionnaire relating to drug treatment and
      bacteriology. The response rate to the questionnaire was 100%. Isoniazid and
      rifampicin were used together in initial therapy in 98.4% of cases, while
      pyrazinamide was prescribed in 90.3% of cases, broadly in keeping with existing
      treatment guidelines. However, considerable variability was observed both in the
      drug regimens employed, and in the duration of initial and continuation phases of
      chemotherapy. Treatment regimens were therefore frequently at variance with
      published recommendations. Among patients prescribed drug regimens other than
      those recommended satisfactory completion of therapy was less common.
      Microbiological confirmation was provided for 84% of cases in which clinical
      samples were submitted. However, in approximately 11% of cases, no clinical
      samples were submitted. Closer adherence to existing treatment guidelines and
      more rigorous pursuit of microbiological confirmation should further improve the
      overall management of pulmonary TB in Scotland.

PMID- 9926143
TI  - Interstitial lung disease in systemic sclerosis: comparison of BALF lymphocyte
      phenotype and DLCO impairment.
AB  - Patients with scleroderma (systemic sclerosis-SSc) frequently develop an
      interstitial lung disease. The role of lymphocytes in fibrosing alveolitis
      preceding lung fibrosis has been established. The purpose of this work was to
      evaluate cell profiles and lymphocyte phenotypes in the bronchoalveolar lavage
      (BAL) fluid and to correlate them with depression in lung function tests detected
      by depletion of diffusing capacity (DLCO). BAL was carried out in 25 untreated,
      non-smoking patients suffering from diffuse scleroderma and in 12 healthy non
      smoking volunteers. For the analysis of lymphocyte sub-sets flow cytometry and
      monoclonal antibodies were used. The following cell sub-types were counted: T
      lymphocytes, B lymphocytes, helper lymphocytes, suppressor/cytotoxic lymphocytes,
      natural killer cells, cytotoxic T lymphocytes and activated T lymphocytes. The
      total cell count was higher in the group of patients with mild and moderate
      impairment in DLCO. The percentage of lymphocytes was greater in patients with
      DLCO lower than 65% of the predicted value since neutrophilia was found in
      patients with severe DLCO depletion, i.e. significant when compared with healthy
      subjects. The proportions of suppressor/cytotoxic lymphocytes and of activated T
      lymphocytes were higher in patients than in controls. The statistical analysis
      revealed significant differences between patients with moderate and mild changes
      in DLCO and the healthy volunteers. A decreased helper/suppressor ratio was
      noticed in these patients. We concluded that the BALF lymphocyte phenotype
      analysis may reflect the features of alveolitis in patients with SSc.

PMID- 9926144
TI  - Salmeterol xinafoate: an analysis of outcomes and cost-effectiveness using a
      primary care database.

PMID- 9926145
TI  - Evaluation of an electronic hand-held spirometer in patients with asthma.
AB  - In this pilot study we assessed patient compliance and acceptability of data
      recorded in the home environment by asthmatics using a Vitalograph 2110
      spirometer which measures peak expiratory flow rate (PEFR) and forced expiratory
      volume in 1 s (FEV1). This meter automatically time and date stamps all
      measurements and can also assess the technical acceptability of results. Data are
      uploaded to a personal computer for review and analysis. We recruited 30 patients
      (10 male and 20 female, age range 21-72 years) from the chest clinic at Guy's
      Hospital (n = 20) and from a GP clinic (n = 10). Patients were asked to record
      spirometry data using the meter at set times (8.00 a.m. and 8.00 p.m.) for 2
      weeks. The spirometer incorporated an alarm to remind patients to take
      measurements. All patients completed the study. Mean (SD) compliance with
      spirometer use was 100.8% (49.9%). Nineteen patients had a compliance rate of
      between 80% and 120% of expected use. Timing of recordings was compared with the
      scheduled times of 8.00 a.m. and 8.00 p.m. Values recorded with +/- 2 h were
      judged as acceptable. For morning recordings 67.4% of all values and for evening
      recordings 71.7% of all values met this criterion. Technical acceptability of
      spirometry data was also assessed by using quality assurance criteria recorded by
      the spirometer. Valid tests were performed for 75.2% of all recordings. Twenty
      two patients performed valid tests for 80-100% of the time. We suggest that the
      use of an electronic meter in the home environment is practical and is likely to
      generate more accurate and reliable data.

PMID- 9926146
TI  - Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish
      experience.
AB  - Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition
      with an estimated prevalence of 1/4500 individuals in Spain. Given this low
      prevalence, it seems useful to accumulate all the information derived from the
      care of these patients. In this context, the Spanish Registry of patients with
      AAT deficiency was founded in 1993; its main objectives were to establish
      guidelines adapted to our country for the treatment and management of AAT
      deficient patients, offer expert support to physicians all over the country
      treating these patients, and provide technical support on the determination of Pi
      phenotyping and genotyping of individuals suspected of being AAT-deficient. From
      1993 to January 1998 the number of enrollees increased from 48 to 223, of which
      216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never
      smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD =
      31%). 83% were index cases who, compared with non-index cases, were older (49 +/-
      11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85%
      vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function
      (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was
      administered to 129 patients (58%). Treated patients had more severe impairment
      in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P
      < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001).
      Characteristics of the patients included are similar to those described for other
      Registries. The Registry has extended knowledge of the disease throughout the
      country and has established local guidelines for treatment and follow-up. It may
      be a valid database for future co-operation in international initiatives.

PMID- 9926147
TI  - Single centre open study to compare patient recording of PRN salbutamol use on a
      daily diary card with actual use as recorded by the MDI compliance monitor.
AB  - The aim of this study was to assess the patients' use of inhaled short acting
      bronchodilators as rescue therapy during a 4-week study period. In this study an
      electronic metered-dose inhaler compliance monitor (MDI-CM) was used to measure
      the time and date of actuations of the device and this information was then
      compared with the patients' self reporting diary card (DC). Salbutamol canisters
      were used in the compliance monitor. The study was approved by the local ethics
      committee, and written informed consent was obtained from all patients. Patients
      aged 18 years and over who were either receiving, or in the investigators opinion
      required, inhaled salbutamol on a PRN basis were enrolled for a 4-week monitoring
      phase during which all rescue salbutamol used was obtained from the MDI-CM.
      Patients were recording their use of salbutamol in the DC each morning and
      evening. There was a 2-week follow-up period following completion of the
      monitoring phase or withdrawal from the study. Forty-four patients were enrolled
      and 35 patients completed the study. The mean age (range) was 43 (20-76) years
      and mean FEV1 2.32 (0.7-4.0) 1, with male:female ratio of 19:25. Comparison of
      MDI-CM and DC recordings showed patients fell into three categories: (1) patients
      who used rescue salbutamol appropriately and whose MDI-CM and DC recordings
      matched closely; (2) patients who used rescue salbutamol for acute relief but
      whose MDI-CM and DC recordings did not correlate and (3) patients whose use of
      rescue salbutamol was inappropriate or erratic according to the MDI-CM but whose
      DC indicated good compliance. This category of patients include those who
      'dumped' all their salbutamol before attending clinic appointments. There was no
      significant difference in the demographic details or the severity of disease in
      the three groups. Recorded use of 'rescue' bronchodilator is frequently used as
      an indicator of efficacy for new anti-asthma therapies. This study comparing
      electronic data monitoring and remembered rescue salbutamol highlights the
      potential errors that can occur without accurate recording systems.

PMID- 9926148
TI  - Exercise training improves recovery in patients with COPD after an acute
      exacerbation.
AB  - Clinical experience suggests that exercise is beneficial for recovery after an
      acute exacerbation in patients with severe chronic obstructive pulmonary disease
      (COPD). The aim of this study was to quantify the clinical benefit of exercise in
      these patients. Twenty-nine inpatients were randomly assigned to a training group
      (n = 15, FEV1 34% pred) or a control group (n = 14, FEV1 38% pred). On ten
      consecutive days, patients in the training group performed a 6-min treadmill
      walking test and, in addition, five walking sessions per day at > or = 75% of the
      respective treadmill walking distance. Patients in the control group performed
      only treadmill walking tests on days 1, 5, and 10. To directly compare the
      possible benefit of exercise training all patients had an exercise test on day 11
      at the same work load as on day 1. In the training group, 6-min walking distance
      increased from 237 to 420 m, in the control group from 230 to 255 m over the 10
      day period which was significantly different (P < 0.0001). Minute ventilation and
      oxygen uptake increased significantly (P < 0.05) in the training but not in the
      control group. When comparing exercise tests on days 1 and 11, minute
      ventilation, oxygen uptake, PaCO2, lactic acid concentration, and Borg scale were
      significantly reduced to achieve the same work load (P < 0.01) only in the
      training group. Intrathoracic gas volume and residual volume decreased, and FEV1
      and vital capacity increased in the training (P < 0.05) but not in the control
      group. Our data demonstrate that exercise training significantly improves the
      exercise capacity in patients with severe COPD after an acute exacerbation of
      their disease.

PMID- 9926149
TI  - The use of a neural network for studying the relationship between air pollution
      and asthma-related emergency room visits.
AB  - To establish the relationship between air pollution levels and bronchial asthma
      associated emergency room (ER) visits, we adapted artificial network technology
      to conduct this study which focused on three different pollutants, sulphur
      dioxide, nitrogen oxide and ozone. The study population was comprised of adults
      presenting to the emergency room of a large metropolitan hospital in Israel
      during a 3-month period with acute exacerbation of bronchial asthma and who had a
      past history of intermittent airway disease compatible with bronchial asthma. The
      range of mean daily pollutants levels for the whole period were: O3 = 15-26
      micrograms m-3, NOx = 36-108 micrograms m-3, NO = 16-70 micrograms m-3, and SO2 =
      11-32 micrograms m-3. The data sets were composed of input air pollution levels
      and output ER visits. The first 126 data sets used for the training phase showed
      that maximal ER visits were mainly associated with the highest cumulative values
      of air pollution and mostly with nitrogen oxide. In phase two, an attempt was
      made to predict ER visits based on air pollution level in 49 data sets. The study
      findings demonstrated that ordinary network technology can be used for learning
      the effect of air pollution ER visits and, although limited in accuracy, to also
      predict future ER visits.

PMID- 9926150
TI  - Improvement in patient compliance with long-term oxygen therapy following formal
      assessment with training.
AB  - In the Department of Respiratory Medicine, North Staffordshire Hospital, patients
      fulfilling the Department of Health criteria for long-term oxygen therapy (LTOT)
      attend a practical teaching session on the use of their oxygen concentrator
      before commencing therapy. In the present study, we have audited the prescribing
      of LTOT in all patients in three health districts in the North West Midlands
      reviewed between June 1992 and July 1994. They were split into two groups. The
      first had the assessment and training programme in the department. Patients in
      the control group had been prescribed LTOT from outside the department without
      any formal training. In both groups of patients information was collated 6 months
      after starting LTOT by means of a questionnaire assessing patients',
      understanding of both their need for oxygen and their disease process, the
      dangers of oxygen therapy and present smoking habit. Objective information about
      the usage of each concentrator was obtained from engineer reports. Thirty-six
      patients (eight from the trained group and 28 controls) died before evaluation at
      6 months. Forty-five patients (29 male, mean age 71 years) received training and
      41 control patients (24 male, mean age 72 years) were evaluated. Thirty-seven
      (82%) patients who had received formal training were using their concentrator for
      greater than 15 h compared with only 18 (44%) of the controls (P = 0.0002). Forty
      two (93%) patients who had received training understood why they were using LTOT
      compared with only 17 (41%) in the control group (P = 0.00001). Although both
      groups had a similar understanding of the dangers of smoking while on oxygen
      therapy, six (15%) of the control group were smoking as compared to only one (2%)
      of the trained group (P = 0.038). One of the control patients had received
      significant facial burns as a direct result of smoking while on oxygen. Further
      efforts are required to ensure that all patients prescribed LTOT should have a
      formal respiratory assessment as well as training to improve compliance and to
      obtain maximal benefits from such therapy.

PMID- 9926151
TI  - Asthma health status measurement in clinical practice: validity of a new short
      and simple instrument.
AB  - Health status (Quality of Life) questionnaires for use in asthma are generally
      too long or complex for routine use. A new short and simple measure of health
      status in asthma has been developed for this purpose. There are two versions, one
      containing 30 items (AQ30) and the other 20 items (AQ20). This study examined
      their cross-sectional and longitudinal properties and compared them with those of
      two established measures--the St. George's Respiratory Questionnaire (SGRQ) and
      the Asthma Quality of Life Questionnaire (AQLQ). Ninety asthmatic patients (mean
      age 46 years) participated. Mean post-bronchodilator forced expiratory volume in
      one second (FEV1) was 73 +/- 25 (SD)% predicted at baseline. Questionnaire data
      were collected twice, 12 weeks apart. Diary records of peak expiratory flow rate
      (PEFR) and daily asthma were kept for 14 days. The new questionnaires each took 3
      min or less to complete. At baseline they correlated well with the SGRQ and AQLQ
      and showed the same pattern of correlations with clinical measures of asthma.
      Change scores for the new questionnaires correlated with those for the
      established measures. There was no advantage of the AQ30 over the AQ20. The AQ20
      provides a simple method for obtaining valid health status estimates of
      asthmatics in routine clinical practice and has properties similar to more
      complex research instruments.

PMID- 9926152
TI  - Outcome of COPD patients performing nocturnal non-invasive mechanical
      ventilation.
AB  - The role of non-invasive nocturnal domiciliary ventilation (NNV) in chronic
      obstructive pulmonary disease (COPD) patients with chronic hypercapnia is still
      discussed. The aims of this study were to evaluate the long-term survival, the
      clinical effectiveness and side-effects of NNV in these patients. Forty-nine
      stable hypercapnic COPD patients on long-term oxygen therapy (LTOT) were assigned
      to two groups: in Group 1, 28 patients performed NNV by pressure support modality
      in addition to LTOT; in Group 2, 21 patients continued their usual LTOT regimen.
      Treatment was assigned according to the compliance to NNV, after an in hospital
      period. Mortality rate, hospital stay (HS) and ICU admissions (IA) were recorded
      in the two groups. HS and IA were compared to those recorded in a similar period
      of follow-back. Lung and respiratory muscle function, dyspnoea, and exercise
      capacity (by 6-min walk test) were evaluated baseline and every 3-6 months up to
      3 yr. Mean follow-up time was 35 +/- 7 months. Mortality rate was not different
      between the two groups: 16, 33, 46% and 13, 28, 50% at 1, 2 and 3 yr in Groups 1
      and 2 respectively. Lung and respiratory muscle function did not significantly
      change over time. A significant increase in 6-min walk test (from 245 +/- 78 to
      250 +/- 88, 291 +/- 75, 284 +/- 89 m after 1, 2 and 3 yr respectively, P < 0.01)
      was observed only in patients undergoing NNV. In comparison to the follow back HS
      significantly decreased in both groups (from 37 +/- 29 to 15 +/- 12 and from 32
      +/- 18 to 17 +/- 11 days/pt/yr in Groups 1 and 2 respectively, P < 0.001) whereas
      IA significantly decreased only in patients performing also NNV (from 1.0 +/- 0.7
      to 0.2 +/- 0.3/pt/yr, P < 0.0001). Addition of NNV by pressure support modality
      to LTOT does not improve long term survival but significantly reduces ICU
      admissions and improves exercise capacity in severe COPD with hypercapnia.

PMID- 9926153
TI  - Mild experimental exacerbation of asthma induced by individualised low-dose
      repeated allergen exposure. A double-blind evaluation.
AB  - Low doses of environmental allergens have been proposed to increase bronchial
      hyperreactivity in sensitised individuals, without causing immediate asthmatic
      reactions. The primary aim of the present study was to evaluate whether repeated
      low doses of allergen, that do not cause overt bronchoconstriction, cause
      augmented non-specific bronchial reactivity. A secondary aim was to evaluate
      whether any changes in reactivity are associated with increased variability of
      lung function, and whether signs of inflammatory activity could be found. To do
      this, mild asthmatic patients without regular symptoms, but with both immediate
      and late reactions in response to a high dose of inhaled cat allergen extract,
      were included in a double blind, placebo controlled, cross-over study in which a
      low dose of allergen was administered on four consecutive days (Monday to
      Thursday). The dose of allergen was individualised for each patient, and was
      calculated to be 25% of the total dose given to produce an immediate and late
      response at screening. Repeated low dose allergen exposure produced a significant
      increase in methacholine reactivity compared to placebo, whereas FEV1 in the
      morning did not significantly change during the allergen week. Each low dose
      allergen exposure caused small changes in FEV1 (approximately 7% drop), which was
      significant vs. placebo only on day 2 (Tuesday). During the allergen week, six of
      eight patients reported asthma symptoms on at least one occasion, and variability
      in lung function, measured with a portable spirometer, was increased. Repeated
      low doses of allergen also produced a significant increase of P-ECP vs. placebo,
      without a significant rise in circulating eosinophils. However, no significant
      changes in circulating CD3, CD4, CD8, CD19, or CD25 cells were found, evaluated
      by FACS analysis. We conclude that low doses of allergen produce signs of a mild
      exacerbation of asthma, including increased bronchial reactivity to methacholine.
      This clinical model may be useful to evaluate both the pathophysiological
      mechanisms of asthma, and the effects of novel anti-asthma drugs.

PMID- 9926154
TI  - Quality of life in elderly patients with COPD: measurement and predictive
      factors.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity in old
      age. It leads to reduced quality of life (QoL), but the factors that contribute
      to this are less understood. There is no consensus on measurement of QoL in
      elderly COPD patients. We assessed (a) factors predicting QoL in elderly COPD out
      patients and (b) specificity (SP), sensitivity (SEN), positive and negative
      predictive values (PPV and NPV) and repeatability of two disease-specific QoL
      instruments, the Chronic Respiratory Disease Questionnaire (CRQ) and the
      Breathing Problems Questionnaire (BPQ) in elderly people. All subjects also
      completed an ADL measure [Nottingham Extended ADL (NEADL)] and a measure of
      psychological well-being [Brief Assessment of Depression Cards (BASDEC)] as well
      as a 6-min walk test. Subjects comprised 96 (56 men) elderly out-patients with
      irreversible COPD aged 70-93 years (mean 78) who were clinically stable for > or
      = 6 weeks. Controls were 55 (23 men) aged 71-90 years (mean 78) with normal lung
      function. All were cognitively intact. Mean FEV1/FVC in COPD subjects was 45.5
      (SE = 1.4)% and for controls was 71.4 (SE = 1.3)%. Repeatability was good for
      both BPQ and CRQ with no significant difference. There were no significant
      differences in specificity and positive predictive values between the two
      questionnaires but BPQ performed better than CRQ with regard to sensitivity (P =
      0.02) and NPV (P < 0.001). A multiple regression analysis was used to identify
      variables that best predicted BPQ and CRQ in COPD subjects. For BPQ predictive
      values were NEADL (P < 0.0001); BASDEC (P < 0.0001); age (P < 0.0001); 6-min walk
      distance (P = 0.001); body mass index (P < 0.05); resting oxygen saturation (P <
      0.05); and household composition (living alone or with relatives, P = 0.05). In
      contrast only the following predicted CRQ: NEADL, BASDEC and resting oxygen
      saturation. Sixteen per cent of the variance in BPQ was accounted for by NEADL
      score, 9% by BASDEC, 4% by age and 3% by 6-min walk distance (total r2 = 0.70).
      It was concluded that: (1) BPQ provides more valid assessment than CRQ of QoL in
      elderly COPD subjects; (2) severity of disease in terms of its impact on QoL is
      not predicted by lung function tests; (3) the most important determinants of QoL
      are ADL score and emotional status.

PMID- 9926155
TI  - Consistent effects of high socioeconomic status and low birth order, and the
      modifying effect of maternal smoking on the risk of allergic disease during
      childhood.
AB  - Birth order, maternal age, gestational age, birth weight, maternal smoking, and
      social class have all been associated with allergic rhinitis, eczema and asthma
      in childhood, but the consistency of independent effects of these exposures in
      relation to all of these allergic conditions has not been investigated. We have
      compared and contrasted the independent effects of these putative risk factors on
      parent-reported hayfever, eczema and wheeze by age 16 years and in the past 12
      months at age 16 using data from the 1970 British birth cohort. The 1970 British
      birth cohort comprised all children born in England, Scotland and Wales in one
      week of April 1970, and follow-up surveys at birth, 5, 10 and 16 years of age
      involved a cumulative total of 17,427 children. We have used data on over 6000
      children with complete data at every stage. Social advantage was a risk factor
      common to each of wheeze at, and hayfever and eczema at and by age 16. Low birth
      order was an independent risk factor for eczema and hayfever at age 16, but not
      for wheeze. However, wheeze at age 16 was significantly increased in relation to
      maternal smoking, with a significant interaction such that the effect of smoking
      was greatest in those of high birth order and, in the absence of maternal
      smoking, low birth order was a risk factor for wheeze at age 16. Social advantage
      and low birth order appear to be the independently consistent determinants of
      atopic disease. Maternal smoking is an additional risk factor for wheeze, which
      applies primarily in low socioeconomic groups.

PMID- 9926156
TI  - Pulmonary function threshold for distinguishing ventilatory- and nonventilatory
      limited patients with airflow obstruction.
AB  - Patients with chronic obstructive pulmonary disease (COPD) may demonstrate great
      variability between results on the pulmonary function test (PFT) compared to
      those on the cardiopulmonary exercise test (CPXT). The purpose of this study was
      to correlate PFT and CPXT indices and to identify PFT threshold values for
      predicting exercise capacity in patients with airflow limitation. Fifty-seven
      patients (48 men and 9 women) of mean age 66.4 +/- 4.8 years with COPD and 40 age
      matched control patients underwent PFT and CPXT. Based on the CPXT results, the
      patients were divided into ventilatory-limited (VL) and nonventilatory-limited
      (NVL), and the findings were correlated with the PFT indices. Linear regression
      analysis was used to determine the relationship between dyspnea index (VEmax/MVV)
      and forced expiratory volume in one second (FEV1). The cutoff value for VL was
      FEV1 < 38% and for NVL FEV1 > 68%. The prominent limiting symptom (61%) in the VL
      group was dyspnea sensation, with leg discomfort presenting in only 14%;
      corresponding rates in the NVL group were 38% and 31%. We conclude that the FEV1
      is a reliable index for distinguishing VL from NVL COPD patients during CPXT at
      two extremes: below 38% of the predicted value (VL) and above 68% of the
      predicted value (NVL).

PMID- 9926157
TI  - Gastroesophageal reflux presented with haemoptysis and carinal erythematous
      lesion resembling in situ carcinoma.
AB  - Gastroesophageal reflux (GER) is often associated with respiratory disorders. We
      report an unusual case of GER presented with haemoptysis. On fibreoptic
      bronchoscopy (FFB) a focal erythematous lesion of the mucosa of the main carina
      was found. Repeated FFB and biopsy excluded in situ neoplasm. Pharmacological
      treatment of GER with sisapride and ranitidine resulted in complete remission of
      the bronchial lesions. To the best of our knowledge haemoptysis with
      bronchoscopic lesions due to the gastroesophageal reflux has not been described
      previously.

PMID- 9926158
TI  - Pulmonary Langerhans' cell histiocytosis following autologous haemopoietic
      progenitor cell transplantation.

PMID- 9926159
TI  - Survival experience of the population needing hospital treatment for asthma or
      COPD at the age of 50-54 years.

PMID- 9926162
TI  - Pitfalls in evaluating mite exposure from house-dust samples.
AB  - Results from vacuum collected samples from a patient's environment may support
      the diagnosis of mite allergy. High estimates of mites or mite allergens do show
      that a patient is exposed. Low estimates are harder to interpret. Estimates may
      be low due to dust dynamics or to the behaviour of the mites, which, according to
      their biology, can be present or almost absent in the samples. A survey is given
      of the nature of these obstacles to proportionality between sample results and
      the exposure which might be experienced by a patient during a period of time. To
      reduce the problems of false-negative estimates of exposures from single samples,
      series of samples collected weeks apart may improve the significance of
      diagnoses.

PMID- 9926161
TI  - Increase in non-specific bronchial hyperresponsiveness without specific response
      to isocyanate in isocyanate-induced asthma: a pilot study.
AB  - Increased non-specific bronchial hyperresponsiveness (BHR) has been reported
      after positive reaction to isocyanates in patients with isocyanate-sensitive
      asthma. The increased responsiveness may, however, also precede the asthma
      attack. We therefore compared non-specific BHR to a cholinergic agent before and
      after exposure to toluene-diisocyanate (TDI) that induced no asthma symptoms in
      11 workers with isocyanate-related asthma. Patients were exposed for 3
      consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min
      1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate
      nor late asthmatic bronchial reaction was observed in any patient after any dose
      of TDI during or after challenge. A significant increase in non-specific BHR was
      noted 24 h after the last dose of TDI challenge, however. This increase was at
      least one doubling dose for seven of 11 patients. In conclusion, our study shows
      that, in patients with isocyanate-induced asthma, exposure to TDI induces a
      slight but significant increase in non-specific BHR in the absence of any
      immediate or late bronchial response to isocyanate. This result, which requires
      further confirmation, may justify a proposal to measure non-specific BHR, even
      after a negative specific inhalation test to TDI, as an additional diagnostic
      element for TDI-induced occupational asthma, to help lower the percentage of the
      undetected occupational asthma cases.

PMID- 9926163
TI  - Glucocorticoid receptor mRNA levels in bronchial epithelial cells of patients
      with COPD: influence of glucocorticoids.
AB  - Glucocorticoids (gcs) are known to be effective in the treatment of asthma. In
      chronic obstructive pulmonary disease (COPD), however, no beneficial effects are
      demonstrated in most patients. Hypothetically, this may be explained by an
      overexpressed beta-glucocorticoid receptor (GR) compared to the alpha-GR. The aim
      of this study was to investigate alpha- and beta-GR mRNA levels and ratios in
      patients with COPD with or without glucocorticoid treatment. GR and, as a
      control, metallothionein (MT) 2 mRNA levels were compared between patients with
      COPD receiving glucocorticoids (COPD + gcs), glucocorticoid naive COPD-patients
      (COPD - gcs) and non-COPD control patients not using gcs. Bronchoscopy was
      performed and bronchial epithelial cells were sampled with brushing. Smoking did
      not influence alpha- and beta-GR levels and ratios, nor the MT2 mRNA expression
      level. The alpha-GR mRNA expression was lower in the COPD - gcs group than in
      controls. Both GR forms were higher in the COPD + gcs patients than in the COPD -
      gcs patients, but not different from the levels measured in the controls. alpha
      1/beta-GR mRNA ratios did not differ between the groups and averaged 1.7,
      suggesting no inhibitory effect of the beta-GR on the alpha 1 form. MT2 levels
      were upregulated in the COPD + gcs patients as compared to the COPD - gcs group,
      indicating a pharmacological glucocorticoid effect. In the present study it is
      demonstrated that basal GR mRNA levels are lower in patients with COPD. Although
      this needs to be investigated further, this might explain, in part, the non
      responsiveness of patients with COPD to gcs.

PMID- 9926164
TI  - The Scottish multi-centre prospective study of bronchoscopy for bronchial
      carcinoma and suggested audit standards.
AB  - Fibre-optic bronchoscopy is widely used to diagnose bronchial carcinoma. There is
      considerable variation in techniques for patient sedation, methods of obtaining
      samples and histopathological yield. We wished to examine variations in practice
      in different centres throughout Scotland and derive realistic audit standards for
      best clinical practice from these results. Diagnostic bronchoscopies from five
      centres were included. Patient details, grade of individual performing the test,
      endobronchial abnormalities, specimens taken and the histocytological yield were
      recorded. A patient satisfaction questionnaire was completed. One thousand eight
      hundred and two bronchoscopies were performed to look for bronchial carcinoma.
      Sedation and anaesthesia techniques varied considerably between centres. There
      were marked differences in patient satisfaction between centres. Nearly twice as
      many females as males would prefer not to have bronchoscopy repeated. Six hundred
      and fifty-eight carcinomas were confirmed by histocytology. Yield was unaffected
      by the grade of doctor performing bronchoscopy. Improving yield may be achieved
      by increasing the number of sampling techniques employed and changing the order
      in which specimens are taken (biopsies first and washings last). Eighty-seven
      percent of endoscopically visible tumours were confirmed histocytologically.
      There was a considerable variation in histological spectra between centres that
      may relate to differences in pathological interpretation rather than actual
      differences in case mix. Suggested audit standards are discussed. This study
      demonstrates the variety of techniques and also the levels of histocytological
      yield and patient satisfaction that can be achieved. Provisional standards of
      practice for this procedure have been agreed with a view to auditing performance
      against these. It is hoped that centres will adopt the methods that are shown to
      achieve the highest standards.

PMID- 9926165
TI  - Comparison of the effects of salmeterol and ipratropium bromide on exercise
      performance and breathlessness in patients with stable chronic obstructive
      pulmonary disease.
AB  - To compare the effects of salmeterol, an adrenergic drug, and ipratropium
      bromide, an anticholinergic drug, on breathlessness and gas exchange during
      exercise in patients with chronic obstructive lung disease (COPD), we performed a
      progressive treadmill exercise test on 15 patients on 3 days (24 h apart), after
      inhalation placebo, ipratropium bromide (120 micrograms) or salmeterol (50
      micrograms) in a randomized fashion. Dyspnoea during exercise was evaluated from
      the regression slope between Borg scale (BS) scores and distance walked each
      minute on the treadmill. The regression was expressed as the distance walked at
      BS score 5, the threshold load of dyspnoea (TLD) and breakpoint load of dyspnoea.
      During and after the exercise, oxygen saturation was monitored by pulse oxymeter
      and we measured the lower SaO2 during exercise and the recovery time of SaO2
      after exercise. In comparison to placebo inhalation we found the same small but
      significant improvement in airflow limitation after salmeterol or ipratropium
      inhalation, also the distance walked on treadmill increased after
      bronchodilators. After bronchodilators the magnitude of oxyhaemoglobin
      desaturation with exercise was similar to that observed after placebo but the
      duration of the recovery from sustained SaO2 desaturation after exercise was
      shorter to the same extent as after ipratropium or salmeterol. Dyspnoeic
      sensation, when assessed by the TLD and by the distance walked at BS score 5, was
      decreased after salmeterol and after ipratropium bromide to a similar extent. We
      conclude that the salmeterol, when given in conventional doses, produces
      significant improvement in the airway obstruction in the recovery of postexercise
      HbO2 desaturation and in dyspnoeic sensation in patients with COPD, effects which
      were similar to those observed after inhalation of the anticholinergic agent
      ipratropium bromide.

PMID- 9926166
TI  - The value of forced expiratory volume in 1 s in screening subjects with stable
      COPD for PaO2 < 7.3 kPa qualifying for long-term oxygen therapy.
AB  - Guidelines on the management of chronic obstructive pulmonary disease (COPD)
      issued by the European Respiratory Society (ERS), British Thoracic Society (BTS),
      American Thoracic Society (ATS), and Department of Health for England and Wales
      (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below
      which arterial blood gas analysis should be performed to determine the presence
      of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement.
      This study aimed to determine the value of FEV1 at these different levels in
      screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable
      COPD. Comparative measures were taken against other lung function tests of volume
      and diffusing capacity. A retrospective analysis of paired lung function and
      arterial oxygen measurements in 491 subjects was made. The positive and negative
      predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS),
      FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were
      determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between
      lung function variables and PaO2 was established. Logistic regression analysis
      was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using
      FEV1 to screen for LTOT requirement produced a high negative predictive value at
      all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1
      < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%,
      FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single
      lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40),
      FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships.
      Logistic regression also placed FEV1 % pred and TLCO % pred as the best
      predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates
      well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa
      was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an
      individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1
      may be used to exclude subjects from further investigation for LTOT and prevent
      unnecessary arterial sampling.

PMID- 9926167
TI  - Refined tuberculosis contact tracing in a low incidence area.
AB  - Our aim was to evaluate the efficacy of a revised tuberculosis (TB) contact
      tracing procedure in South Glamorgan whereby routine annual radiological
      surveillance was abandoned and contacts were either discharged or referred to
      chest clinic following their initial screening. We reviewed and evaluated data
      from the TB contact tracing clinic, the Public Health Service Mycobacterium
      Reference Unit, Cardiff and the Consultant in Communicable Diseases Control,
      South Glamorgan Health Authority and compared these results with those of our
      previous study. One hundred and three index cases and 732 contacts were
      identified. Seven hundred and seven contacts, 526 close and 181 casual, were
      screened, of whom 102 casuals should not have been. One hundred and sixty-one
      contacts were given BCG vaccination. Fifty-four contacts were referred to the
      chest clinic. Seven cases of TB were detected, all in young, unvaccinated, close
      contacts of pulmonary disease. Twenty-one contacts were given chemoprophylaxis,
      20 of whom were close contacts of pulmonary TB and one of extrapulmonary disease.
      Five contacts who were screened and initially discharged developed TB later: in
      two the protocol had not been followed and three presented with extrapulmonary
      TB. Compared with the results of the previous protocol fewer contacts were
      unnecessarily screened and referrals to the chest clinic increased, as did the
      number given chemoprophylaxis. The case finding rate is similar to that found
      prior to the revision of the protocol. The yield from tracing casual contacts
      continues to be nil. It is very low in contacts of extrapulmonary disease. When
      the protocol was followed no case of pulmonary TB was missed. The revised
      protocol seems to be as effective as the previous, more complex protocol. In our
      area, one of low incidence of TB, screening of casual contacts and of contacts of
      extrapulmonary TB is not cost-effective. We will concentrate even more on
      screening close contacts of pulmonary TB.

PMID- 9926168
TI  - The impact of spontaneous pneumothorax, and its treatment, on the smoking
      behaviour of young adult smokers.
AB  - The pneumothorax, and its often invasive treatment, are impressive events in
      otherwise healthy young patients. The relationship between smoking behaviour and
      the idiopathic spontaneous pneumothorax (ISP) is explained to the patients. The
      objective of the study was to analyse whether smoking behaviour of patients is
      influenced by the ISP (re-) event, and its treatment. Of 145 consecutive ISP
      patients (1991-1995), 112 were tobacco smokers at time of the first ISP. Of the
      112, 106 participated in a confidential telephone questionnaire survey combined
      with retrospective medical record analysis. Smoking cessation and reduction
      percentage related to ISP events, and its treatment, were the outcome
      measurements. All patients (mean age 28.8 years at the first ISP) were aware of
      the relationship between smoking, and ISP at time of the first ISP. Age, pack
      years, and different treatment modalities had no influence on smoking cessation
      or reduction. Some 86.2% of the male and 80.8% of the female patients continued
      smoking after the first ISP, despite the known relationship between smoking, and
      contracting spontaneous pneumothorax, and despite its often invasive treatment.
      In the group of recurrent pneumothorax events 73.3% continued smoking.

PMID- 9926169
TI  - Time course of symptom resolution in patients with community-acquired pneumonia.
AB  - The majority of patients with community-acquired pneumonia are at low risk for
      short-term mortality or serious morbidity and are increasingly managed in the
      outpatient setting. Efforts to improve the quality of care for these patients
      will need to measure patient outcomes such as disease-specific symptom
      resolution. The aims of this study were to (1) develop a self-administered daily
      version of a symptom questionnaire for patients with pneumonia, (2) measure the
      reliability of this instrument, and (3) provide estimates for recovery rates
      based on symptom resolution in a cohort of low-risk patients with community
      acquired pneumonia. This study was conducted as part of a prospective study of a
      new emergency department protocol for pneumonia at the Massachusetts General
      Hospital. Eligible study subjects included all adult patients with pneumonia
      presenting to the emergency department with a predicted low risk of short-term
      mortality. The main outcome measures were based on a new five item symptom
      questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and
      fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from
      the time of diagnosis of pneumonia. The symptom questions were also administered
      during patient interviews on days 0, 7, 14 and 28 in order to assess the
      questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to
      participate in this study. The mean intra-class reliability coefficient of the
      symptom questionnaire was 0.75. The median times to resolution of individual
      symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty
      five percent of patients had at least one symptom still present at the end of the
      28-day study period. We found that a daily self-report questionnaire is a
      reliable measure of symptom resolution for patients with pneumonia. Full
      resolution of symptoms takes more than 28 days for a significant proportion of
      patients with pneumonia.

PMID- 9926170
TI  - Acupuncture in treatment of stable asthma.
AB  - Previous studies of acupuncture in asthma have reported conflicting results, some
      claiming benefit for some patients. We conducted a randomized, double-blind
      (patient and evaluator) study in 23 non-smoking asthmatics (10 M; 13 F) aged 43
      +/- 15 years with forced expiratory volume in 1 s (FEV1) 59 +/- 16% pred. After
      initial assessment (respiratory function tests and Asthma Quality Life
      Questionnaire) patients were randomized to receive either 'real' or 'sham'
      acupuncture. The measurements were repeated within 1 h and after 2 weeks.
      Patients were recording peak expiratory flow rate (PEFR) throughout the period of
      the study. After 2 weeks patients who received 'real' treatment on the first
      visit received 'sham' treatment and vice versa. The measurements were again
      repeated within 1 h and after 2 weeks. There was no improvement in any aspects of
      respiratory function measured after either form of acupuncture. Despite this
      there was a significant improvement in AQLQ and parallel reduction in the usage
      of bronchodilators. We concluded that in some patients acupuncture could be
      useful in improving quality of life and reducing the need for using
      bronchodilators either by having a placebo effect or that the exact site of
      needle puncture on the chest is unimportant.

PMID- 9926171
TI  - A short outpatient pulmonary rehabilitation programme: immediate and longer-term
      effects on exercise performance and quality of life.
AB  - Pulmonary rehabilitation is widely available in North America and parts of Europe
      for patients with chronic obstructive pulmonary disease (COPD). Here, we describe
      the feasibility and benefits of providing a comprehensive but cost effective
      pulmonary rehabilitation programme in a U.K. district general hospital. Two
      hundred and sixty-seven patients with respiratory disability were referred for
      pulmonary rehabilitation. Patients were assessed and recruited onto a 7 week
      outpatient-based pulmonary rehabilitation programme including elements of
      exercise and education without longer term maintenance. Exercise performance was
      measured by the shuttle walking test and a treadmill endurance test, and quality
      of life as measured by two disease specific questionnaires, the Breathing
      Problems Questionnaire and the Chronic Respiratory Disease Questionnaire. Of 267
      patients referred between 1993 and 1996, 132 (110 with COPD) have completed
      rehabilitation and could be evaluated. For all graduates, shuttle distance
      increased by 58 m (27%) and treadmill endurance time increased by 15.9 min
      (294%). The Breathing Problems Questionnaire proved sensitive to changes in
      quality of life in some domains. The Chronic Respiratory Disease Questionnaire
      showed significant improvements in all domains in a sub-set of 57 patients who
      completed it. Longer term follow-up of 49 patients at a mean of 10.3 months
      following pulmonary rehabilitation revealed that previous gains in exercise
      performance and quality of life were maintained with improvements in shuttle
      walking distance of 33 m (14% over baseline) and endurance time of 16 min (280%
      over baseline). The Breathing Problems Questionnaire showed no overall change but
      the Chronic Respiratory Disease Questionnaire showed continued improvement in a
      small number of patients. We therefore concluded that a short outpatient based
      pulmonary rehabilitation programme without a maintenance element has produced
      significant gains in exercise performance and quality of life for 132 patients at
      a district general hospital in the U.K.

PMID- 9926172
TI  - A re-audit of pulmonary function laboratories in the West Midlands.
AB  - In 1991 the West Midlands Pulmonary Function Audit Group examined the consistency
      between pulmonary function laboratories in the West Midlands. Three healthy
      subjects visited 22 centres and performed a standard set of pulmonary function
      tests. Demographic data on nine hypothetical subjects was also supplied for the
      laboratories to produce predicted values. Equipment was checked for accuracy
      using standard methods. The 1991 audit revealed significant inter-laboratory
      variability. Sources of error were identified and after consultation,
      recommendations were made to improve consistency. In addition, national and
      regional training workshops were organized for laboratory staff. In 1995 the
      audit was repeated using the same three subjects. Significant differences
      continued for all predicted results except for residual volume (RV) and forced
      vital capacity (FVC) and for all measured results except for functional residual
      capacity (FRC). However, improvements in the coefficient of variation were seen
      compared with 1991 for predicted forced expiratory volume (FEV1), total lung
      capacity (TLC), gas transfer (TLCO), FVC, FRC and RV. Similar improvements were
      seen in measured results for FEV1 and FVC. Increased variation was seen for
      predicted corrected transfer factor (KCO) and actual RV. The majority of
      variables in the 1995 audit had a coefficient of variation of less than 5%
      between laboratories. Analysis of the predicted results from the hypothetical
      subjects continued to show unacceptable variation reflecting continuing computer
      algorithm inconsistency. The improvements seen are encouraging and suggest that a
      regular audit programme is worthwhile.

PMID- 9926173
TI  - Bimodal granulocyte transit time through the human lung demonstrated by
      deconvolution analysis.
AB  - The lungs are an important site of granulocyte pooling. The aim of the study is
      to quantify pulmonary vascular granulocyte transit time using deconvolution
      analysis, as has previously been performed to measure pulmonary red cell transit
      time. Granulocyte and red cell studies were performed in separate groups of
      patients. Both cell types were labelled with Tc-99m, which for granulocyte
      labelling was complexed with hexamethylpropyleneamine oxime (HMPAO). The red cell
      impulse response function (IRF) was monoexponential with a median transit time of
      4.3 s. The granulocyte IRF was biexponential in 19 of 22 subjects, 18 of whom had
      systemic inflammation (inflammatory bowel disease, systemic vasculitis or graft
      vs-host disease) and four were controls without inflammatory disease. The median
      transit time of the fast component ranged from 20 to 25 s and of the slow
      component 120-138 s in the four patient groups. The fraction of cells undergoing
      slow transit correlated significantly with (a) mean granulocyte transit time and
      (b) the fraction showing shape change in vitro. We conclude that granulocyte
      transit time through the pulmonary circulation is bimodal and that shape-changed
      (activated) cells transit more slowly that non-activated cells. The size of the
      fraction undergoing slow transit is closely related to mean granulocyte transit
      time and is an important determinant of the size of the pulmonary vascular
      granulocyte pool.

PMID- 9926174
TI  - Pulmonary fibrosis in polymyositis with the Jo-1 syndrome: an unusual mode of
      presentation.

PMID- 9926175
TI  - Non-invasive ventilation in hypercapnic respiratory failure secondary to
      sclerodermic chest wall restriction.

PMID- 9926176
TI  - Pleuropulmonary disease as a side-effect of treatment with bromocriptine.

PMID- 9926177
TI  - Pulmonary edema as a result of chronic upper airway obstruction.
AB  - This is the first case of an adult who developed recurrent pulmonary edema as a
      result of unrecognized chronic upper airway obstruction due to polyarticular
      juvenile rheumatoid arthritis. The case highlights the importance of considering
      upper airway involvement in the differential diagnosis of sedentary patients with
      arthritic joint disease and breathing difficulties.

PMID- 9926178
TI  - Can rocuronium replace succinylcholine in a rapid-sequence induction of
      anaesthesia?

PMID- 9926179
TI  - A large simple randomized trial of rocuronium versus succinylcholine in rapid
      sequence induction of anaesthesia along with propofol.
AB  - BACKGROUND: Rocuronium has an onset of action more rapid than other non
      depolarizing neuromuscular blocking agents, but it is unclear whether it and
      succinylcholine give equivalent intubating conditions during rapid-sequence
      induction of anaesthesia. We performed this study to answer the question--are
      there clinically relevant differences between the use of rocuronium and
      succinylcholine to secure acceptable intubating conditions during rapid-sequence
      induction of anaesthesia with propofol? METHODS: Anaesthesia was induced using
      propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were
      undergoing either elective or emergency surgery. Propofol was followed
      immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg
      (randomly selected). Fifty seconds after the end of muscle relaxant injection
      laryngoscopy was performed and intubating conditions were graded by an
      experienced anaesthetist blind to the muscle relaxant allocation. This study
      design was selected so that a 10% difference in clinically acceptable intubating
      conditions between drugs would be detectable. RESULTS: In this setting rocuronium
      1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6
      mg/kg. The incidence of clinically acceptable intubating conditions with
      rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1%
      respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%). CONCLUSION:
      Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of
      anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.

PMID- 9926180
TI  - Time dependency of the ratio of umbilical vein/maternal artery concentrations of
      vecuronium in caesarean section.
AB  - BACKGROUND: The ratio of umbilical vein (UV) and maternal artery (MA)
      concentrations of vecuronium may more accurately determine the placental transfer
      ratio during caesarean section. This ratio potentially correlates with the time
      from induction of anaesthesia to delivery (I-D time). The aim of this study was
      to determine the UV/MA ratio of vecuronium and its relationship with the I-D
      time. METHODS: Eighteen pregnant women at full term undergoing caesarean section
      were studied. The parturient was given intravenously 0.01 mg/kg vecuronium as a
      priming dose, followed 180 s later by 0.11 mg/kg vecuronium as an intubation dose
      and 4 mg/kg thiamylal. The time from the injection of the intubation dose to the
      clamping of the umbilical cord was regarded as the I-D time. At the time of
      clamping the umbilical cord, blood samples were collected and the UV and MA of
      vecuronium were measured. RESULTS: The UV/MA ratio and the I-D time, expressed as
      the mean (SD), were 0.056 (0.016) and 280 (57) s, respectively. The regression
      equation indicated y = 0.0083 + 0.00017 x (R2 = 0.381, r = 0.617, P = 0.0063, I-D
      time (s) = x, UV/MA = y). CONCLUSION: The present study demonstrated that the
      UV/MA ratio of vecuronium as an index of the placental transfer becomes smaller
      as the delivery time after injection of this drug becomes shorter during
      caesarean section.

PMID- 9926181
TI  - Peroperative treatment with i.v. ketoprofen reduces pain and vomiting in children
      after strabismus surgery.
AB  - BACKGROUND: Strabismus surgery is associated with both pain and vomiting.
      Ketoprofen is widely used in adults to treat acute pain, but there are only few
      reports of its use in children. This randomised, double-blind, placebo
      controlled, parallel group study was designed to investigate the analgesic effect
      of i.v. ketoprofen and its effect on the incidence of vomiting in children after
      day-case strabismus surgery. METHODS: Fifty-nine ASA 1 children, aged 1-12 years,
      entered the study. After premedication with diazepam and glycopyrronium,
      anaesthesia was induced with fentanyl and propofol and maintained with
      isoflurane. After induction the children in the ketoprofen group received 1 mg kg
      1 ketoprofen followed by an infusion of 1 mg kg-1 ketoprofen over 2 h. In the
      placebo group, children received 0.9% saline. The postoperative pain was assessed
      by the Maunuksela pain score (0 = no pain, 10 = worst possible pain). All
      children received fentanyl as a rescue analgesic if the Maunuksela score was > or
      = 3. RESULTS: In the ketoprofen group the number of fentanyl doses was smaller
      compared to the placebo group (median 1, quartiles (0-2) vs. 2 (1-3), P = 0.047).
      The children in the ketoprofen group had less pain at 30 min (P = 0.02) and the
      worst pain observed in the post anaesthesia care unit was lower (3 (0-6) vs. 5 (3
      8), P = 0.035). The incidence of vomiting was less in the ketoprofen group
      compared to the placebo group (17% vs. 41%, P = 0.036). No serious adverse
      reactions occurred. CONCLUSION: We concluded that ketoprofen administered i.v.
      during the operation produced analgesia and reduced opioid consumption and the
      incidence of vomiting in children after strabismus surgery.

PMID- 9926182
TI  - Clinical evaluation of low-flow sevoflurane anaesthesia for paediatric patients.
AB  - BACKGROUND: Sevoflurane expenditure, inspired gas humidity, temperature, soda
      lime temperature, and compounds A and B were measured during high and low fresh
      gas flow anaesthesia in paediatric patients. METHODS: Sixty ASA 1 or 2 paediatric
      patients were randomly allocated to two groups: low-flow circle anaesthesia (LFA)
      patient group (n = 30) and high-flow circle anaesthesia (HFA) patient group (n =
      30). Initial fresh gas flow (FGF) was 4l.min-1 of nitrous oxide and 2l.min-1 of
      oxygen in both groups. This FGF of 6l.min-1 was maintained in the HFA group.
      After 10 min of HFA, the FGF was reduced to 600 ml.min-1 (nitrous oxide and
      oxygen 300 ml.min-1 each) in the LFA group. RESULTS: Sevoflurane expenditure
      during LFA was about 1/7 of that during HFA (3.3 +/- 0.2 ml.h-1.vol.%-1 compared
      to 22.8 +/- 0.6 ml.h-1.vol.%-1, mean +/- SEM, respectively). Absolute humidity in
      the LFA patients was 4 times higher than that in the HFA patients (22.8 +/- 2.4
      g.m-3 and 5.6 +/- 3.4 g.m-3 respectively). There was no significant difference in
      the inspiratory gas temperature between the LFA (28.5 +/- 0.6 degrees C) and HFA
      (26.9 +/- 1.3 degrees C) groups. There was significant difference in the mean
      highest soda lime temperature between the LFA (35.5 +/- 1.2 degrees C) and HFA
      (28.7 +/- 1.2 degrees C) groups. The mean highest concentration of compound A was
      12.2 +/- 3.8 ppm in the LFA group. The mean highest concentration of compound B
      was less than 1 ppm. Compounds A and B were below detectable level in the HFA
      group. CONCLUSION: In conclusion, sevoflurane used for paediatric patients in a
      circle system with a fresh gas flow of 0.6l.min-1 resulted in a significantly
      reduced sevoflurane expenditure, higher inspired absolute humidity, but not
      temperature, compared to a fresh gas flow of 6l.min-1. Low levels of compounds A
      and B were detected.

PMID- 9926183
TI  - Pain on injection of propofol: the mitigating influence of metoclopramide using
      different techniques.
AB  - BACKGROUND: Metoclopramide administered intravenously (i.v.) immediately before
      injection of propofol, after mixing with propofol, or after a rubber tourniquet
      for 1 min before propofol injection will reduce pain induced by propofol
      injection. In this study, these three different techniques in reducing propofol
      injection pain with metoclopramide were compared with lidocaine or saline to
      evaluate the most effective method in reducing propofol injection pain. METHODS:
      In a randomized, semi-double-blind treatment, 175 patients were included into
      this study. Patients in group A were pretreated with metoclopramide 10 mg i.v.
      before propofol (2 mg/kg) induction. Patients in group B were induced with a
      mixture of propofol and metoclopramide. Patients in group C were pretreated with
      metoclopramide i.v. with a rubber tourniquet on the arm for 1 min followed by
      propofol administration. Groups D and E were identical to group C except for the
      replacement of pretreatment with either lidocaine (40 mg) or saline,
      respectively. RESULTS: Groups A, C and D (with active pain prophylaxis) showed a
      significantly less incidence of pain than the saline control group (E) as
      propofol was injected. There was no significance difference between
      metoclopramide and lidocaine in reducing propofol injection pain using a
      tourniquet technique. The intensity of the propofol injection pain (verbal pain
      score) was stronger with saline as compared with the other groups. CONCLUSIONS:
      We conclude that i.v. retention of metoclopramide with tourniquet is as good as
      lidocaine and may be a useful alternative for reducing pain on propofol
      injection.

PMID- 9926185
TI  - Does preoperative night pulse oximetry provide a reliable baseline?
AB  - BACKGROUND: Postoperative hypoxaemia may be detected by pulse oximetry monitoring
      of the arterial haemoglobin saturation (SpO2). The SpO2-values obtained on the
      preoperative night are presumed to represent baseline values for the patients.
      The aim of this study was to evaluate the possible difference between nocturnal
      SpO2-values in the patient's home and in the hospital before operation. METHODS:
      We included 20 patients, 60 years or older, who underwent continuous monitoring
      of SpO2 on one night in the patient's home and on the night following
      hospitalisation before surgery. The alarms were turned off and the values were
      not accessible to the hospital staff. The SpO2 value was stored every 10 s. We
      described the general oxygen saturation level using the median of all valid
      values and we calculated the number of valid SpO2-values at 3 levels: above 90%,
      between 86 and 90%, and below 86%. RESULTS: The number of valid SpO2-values at
      home and in the hospital were 2186 and 2330, respectively; the median value was
      96% on both occasions. Only 0.36% of the values were below 91% on the two
      occasions and there were no statistically significant differences between the
      number of SpO2-values at any of the considered levels. CONCLUSION: Arterial
      oxygen saturation values measured on the preoperative night in the hospital seem
      reliable as baseline values for elderly patients.

PMID- 9926184
TI  - The effects of tramadol on postoperative nausea, vomiting and headache after ENT
      surgery. A placebo-controlled comparison with equipotent doses of nalbuphine and
      pethidine.
AB  - BACKGROUND: Opioids given as adjuncts to balanced inhalational anaesthesia
      augment postoperative nausea and vomiting (PONV). Tramadol, equipotent to
      pethidine, does not depress respiration, but can cause an increase in blood
      pressure and headache via its monoaminergic actions. Nalbuphine, ten times as
      potent as pethidine, has a ceiling respiratory depressant and ceiling analgesic
      effect at > 0.3 mg.kg-1. We compared the effects of equipotent doses of tramadol
      and nalbuphine (3.0 and 0.3 mg.kg-1, respectively) given as analgesic with
      induction of anaesthesia on emesis during recovery from anaesthesia and on PONV
      and headache until 24 h after ENT surgery, using saline (0.2 ml.kg-1) and an
      equipotent dose of pethidine (1.5 mg.kg-1) as controls. METHOD: The study
      population (N = 281) comprised 4 comparable subgroups (N = 69 to 71 each).
      Anaesthetic medications were standardised. Emesis during recovery from
      anaesthesia and nausea, vomiting, retching, headache and administrations of
      antiemetic and analgesics until 24 h after surgery were recorded. RESULTS: Emesis
      and antiemetic requirements during recovery from anaesthesia were similar and
      infrequent in each group, as were the incidences of nausea alone (3 to 5%),
      vomiting alone (17 to 31%), and nausea with vomiting (10 to 22%) during the first
      24 h after surgery. However, any complaint of PONV was least frequent in the
      saline and pethidine groups (32% and 37%, respectively) and most frequent in the
      tramadol and nalbuphine groups (49% and 52%, respectively; P < 0.05 versus
      saline, both comparisons; P = NS versus pethidine, both comparisons). The times
      to onset and severity of PONV were similar in each group, but patients given
      nalbuphine most frequently (P < 0.025) needed rescue antiemetic to treat PONV.
      Headache occurred with similar frequency in each group. CONCLUSION: It is
      concluded that tramadol, nalbuphine and pethidine have similar emetic effect in
      the doses and manner used, and that tramadol does not increase the incidence of
      post-operative headache when used as peroperative analgesic.

PMID- 9926186
TI  - Effect of experience with spinal anaesthesia on the development of post-dural
      puncture complications.
AB  - BACKGROUND: This clinical study was conducted in order to investigate the effect
      of operator experience with spinal anaesthesia (SA) on development of postural
      post-dural puncture headache (PPDPH) and postoperative backache. METHODS: The
      study was a cohort study of the first 100 SA performed by each of 5 trainees in
      anaesthesiology at the very beginning of their training period. SA was conducted
      with assistance and guidance according to usual departmental practice. In each
      SA, data regarding level of puncture, needle size, number of punctures, use of
      introducer and infiltration anaesthesia were recorded. In addition, usual
      problems and complications connected with dural puncture were registered. A
      visual analogue scale was used to record how difficult the procedure was
      experienced by the trainees. Postoperatively, the patients were contacted by the
      same trainee, usually by telephone. A semi-structured interview was conducted
      where occurrence and duration of headache, backache and other complaints were
      recorded. Headache was classified as PPDPH or non-PPDPH, and intensity of the
      headache was registered using a numerical rating scale (NRS) from 0 to 10.
      RESULTS: Five hundred SA in 495 patients with a mean age of 61.3 years were
      included in the study. Of these, 394 patients were completely followed-up
      postoperatively; the main reason for the drop-out was patient-related factors
      such as advanced age and dementia. Headache occurred in 56 patients
      postoperatively. PPDPH was diagnosed in 33 and non-PPDPH occurred in 23 patients.
      Postoperative backache was experienced by 27 patients. No significant effect
      experience with SA could be found regarding the occurrence of postoperative
      complications; 16 compared to 17 patients with PPDPH were found in the first and
      the last half of patients. A marked inter-individual difference in the occurrence
      of PPDPH was found in the patients treated by the 5 trainees. CONCLUSIONS: We
      could not demonstrate an effect of experience and training on development of
      complications after SA with regard to PPDPH and backache.

PMID- 9926187
TI  - Patient-controlled analgesia with oxycodone in the treatment of postcraniotomy
      pain.
AB  - BACKGROUND: Moderate to severe pain occurs after craniotomy in 60% of patients.
      We evaluated the feasibility and safety of patient-controlled analgesia (PCA)
      with oxycodone in neurosurgical patients, and compared the efficacy of
      paracetamol with ketoprofen. METHODS: In the study there were 45 patients, who
      received either paracetamol 1000 mg or ketoprofen 100 mg three times a day.
      Oxycodone-boluses 0.03 mg/kg were given by PCA-device maximally three times an
      hour, lock-out time 10 min. The amount of oxycodone used, pain scores and side
      effects were recorded. RESULTS: The ketoprofen group required less oxycodone than
      the paracetamol group (medians 37.1 mg vs 19.6 mg, P < 0.05). The VAS scores were
      comparable between the groups at the beginning of the study, during the first
      postoperative evening and the next morning, but the paracetamol group had a
      higher score at the conclusion of the study (P < 0.05). The patients in both
      groups were equally satisfied with the pain relief. There were no differences in
      side-effects between the groups. CONCLUSIONS: PCA with oxycodone is a suitable
      method for pain control after craniotomy. No progressive hypoventilation,
      desaturation or excessive sedation were encountered. Ketoprofen appeared to be
      more effective than paracetamol.

PMID- 9926188
TI  - Intact proprioception and control of labour pain during epidural analgesia.
AB  - BACKGROUND: Accurate proprioception is critical while walking, yet an ambulatory
      epidural regimen that provides adequate analgesia for labour while simultaneously
      preserving proprioceptive input has not been described. METHODS: Sixty
      primigravidae in established labour received bupivacaine 15 mg (15 ml of 0.1%
      w/v) and fentanyl 100 micrograms through a lumbar epidural catheter. Clinical
      assessment of dorsal column sensory function included: vibration sense, distal
      proprioception and the Romberg test, and were all performed before catheter
      insertion and 30 min after the study bolus. Sensory modalities were also tested
      compared to an unblocked dermatome. Pain was scored on a 0-10 cm visual analogue
      scale (VAS) before and 30 min after induction. Intensity of the motor block was
      tested using a modified Bromage score (grade 1-6). RESULTS: The study bolus
      provided reliable analgesia with 43 parturients attaining a VAS pain score of
      zero. Mean duration of analgesia was 67.5 min (SD 22.85). All parturients
      retained the ability to perform a partial knee bend while standing (grade 6). No
      mothers exhibited impaired distal proprioception, altered vibration sense or a
      positive Romberg sign. CONCLUSION: This study confirms that the addition of
      lumbar epidural fentanyl 100 micrograms to 15 mg of epidural bupivacaine provides
      good control of labour pain with no motor block and establishes that this
      combination preserves dorsal column sensory function.

PMID- 9926189
TI  - Intra-articular buprenorphine after knee arthroscopy. A randomised, prospective,
      double-blind study.
AB  - BACKGROUND: Demonstration of peripheral opioid receptors in inflamed synovia
      supports the concept of peripheral opioid analgesia. The aim of this study was to
      evaluate the analgesic effect of intra-articular administration of buprenorphine
      after knee arthroscopy. METHODS: In a double-blind randomised trial, 48 patients
      were assigned to four groups: group A patients received buprenorphine 100
      micrograms i.a. and NaCl 0.9% i.m., group B patients received bupivacaine 0.25%
      50 mg i.a. and NaCl 0.9% i.m., group C patients received NaCl 0.9% i.a. and
      buprenorphine 100 micrograms i.m., and group D patients received NaCl 0.9% i.a.
      and NaCl 0.9% i.m. Intensity of postoperative pain was evaluated by VAS at
      recovery (T0) and 1, 3, 6, 12, 24 h after operation (T1, T2, T3, T4, T5), at rest
      and during passive 10 degrees knee flexion. Total analgesic requirements and side
      effects related to study drugs were recorded. RESULTS: The VAS scores were
      significantly higher in groups C and D than in group A and B patients. The
      differences were significant at T0, T1, T2 and T3. At T1, group C and D patients
      had greater analgesic requirement than groups A and B. No patients developed side
      effects. CONCLUSION: Intra-articular buprenorphine and i.a. bupivacaine, both
      produced equally good postoperative pain control and allowed a significant
      reduction of analgesic requirement after knee arthroscopy.

PMID- 9926191
TI  - Segmental pulmonary vascular responses to changes in pH in rat lungs: role of
      nitric oxide.
AB  - BACKGROUND: Respiratory or renal failure is associated with changes in blood pH.
      Changes in pH may have profound effects on vascular tone and reactivity. Site of
      action of acidosis in the pulmonary vasculature and the role of nitric oxide
      production remain unclear. METHODS: We utilized isolated rat lung preparation
      perfused with autologous blood (Hct = 20%, flow rate = 33 ml/min), and
      investigated the effect of acidosis and alkalosis (induced by ventilation with
      high and low inspired CO2) on vascular resistance and the role of nitric oxide
      during resting and elevated tone conditions. Changes in resistance were described
      in terms of small and large arteries and veins, using the vascular occlusion
      technique. RESULTS: Acidosis (Pco2 = 66.7 +/- 0.7 mmHg, pH = 7.17 +/- 0.01, Po2 =
      255 +/- 3 mmHg) caused vasoconstriction under resting and increased vascular tone
      conditions (U46619-induced). The changes in resistance occurred primarily in the
      small arteries. In contrast, alkalosis (Pco2 = 20.1 +/- 0.3 mmHg, pH = 7.61 +/-
      0.01, Po2 = 244 +/- 3 mmHg) caused vasodilation only at elevated tone conditions.
      Nitro-L-arginine (LNA), an inhibitor of nitric oxide synthase, increased vascular
      resistance slightly but did not modulate the responses to pH, suggesting that
      such responses are not nitric oxide dependent. During KCl-induced contraction,
      the effects of pH were abolished. CONCLUSIONS: We conclude that in rat lung,
      acidosis causes an increase in pulmonary vascular resistance at normal and
      elevated tone conditions. Furthermore, the response is limited primarily to the
      small arteries, and is not mediated by nitric oxide. Alkalosis tends to cause the
      opposite effects. The effects of acidosis and alkalosis were abolished when
      vascular tone was elevated with a low dose of KCl, suggesting that vascular
      response to pH may involve changes in membrane potential.

PMID- 9926190
TI  - Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock.
      Effects of nitric oxide synthase inhibition.
AB  - BACKGROUND: Inhibition of nitric oxide synthase (NOS) has been claimed to be
      beneficial in septic shock. We investigated the overall and regional effects of a
      NOS-inhibitor on perfusion and metabolism during severe endotoxic shock. METHODS:
      Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were
      placed around the portal vein, the hepatic artery, and the superior mesenteric
      artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an
      infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after
      the start of endotoxin while 7 animals served as controls and received endotoxin
      only. Six animals were sham operated with no further intervention. RESULTS:
      Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did
      not increase arterial blood pressure, but deepened the fall in cardiac output and
      enhanced the increase in systemic and pulmonary vascular resistance. The infusion
      of endotoxin caused a decrease in flows in all regions. The addition of L-NAME
      induced a further decrease in the mesenteric artery flow only. L-NAME had no
      additional effect on hepatic artery flow ratio, while a transient decrease was
      seen in mesenteric flow ratio. Portal flow ratio decreased in the control group
      only. Global as well as regional oxygen extraction increased in both groups, more
      so in the L-NAME group. Lactate levels increased with no differences between the
      groups. CONCLUSION: In hypodynamic endotoxic shock, L-NAME infusion enhanced
      pulmonary vasoconstriction and increased left ventricular afterload. The
      resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on
      global and mesenteric blood flow and metabolism were similar, while L-NAME had no
      additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric
      oxide does not seem to be a major factor in the preservation of hepatic perfusion
      during unresuscitated endotoxic shock.

PMID- 9926192
TI  - Alterations of bacterial clearance induced by propofol.
AB  - BACKGROUND: The purpose of the study was to investigate the potential influence
      of the anaesthetic agent propofol on immune function in terms of systemic
      clearance and organ distribution of injected Escherichia coli in a rabbit model.
      METHODS: Defined numbers of E. coli (1.3 x 10(8) colony-forming units, CFU) were
      injected intravenously 1 h after starting a 4-h infusion of the anaesthetic
      propofol (2 ml.kg-1.h-1, Disoprivan 1%; n = 6)) or after saline application (n =
      6). As propofol is formulated in a 10% lipid emulsion, the lipid vehicle
      Intralipid (2 ml.kg-1.h-1; n = 6) alone was investigated in a separate group.
      Parameters monitored were arterial pressure and rates of bacterial elimination
      from the blood. Three hours after bacterial injection, the animals were killed,
      and tissue samples of liver, spleen, lung, and kidney were collected for
      microbiological examinations. RESULTS: Compared to saline-treated animals,
      infusion of propofol induced increased accumulation of E. coli in lung and
      spleen, thus reflecting reticuloendothelial system dysfunction. CONCLUSION: As
      the lipid emulsion by itself induced the same effects, the impaired immune
      function due to propofol is thought to be attributed to its solvent Intralipid.

PMID- 9926193
TI  - Heat stress produces an early phase of protection against oxidative damage in
      human muscle.
AB  - BACKGROUND: It has been rarely reported that heat stress induces an early phase
      of protection against oxidative damage, whereas a delayed phase of protection is
      shown in heat stress. To explore the early effect of heat stress against
      oxidative damage, we evaluated the changes in contractility, lipid peroxidation,
      and ultrastructure induced by hydrogen peroxide (H2O2) with or without heat
      stress (HS) in human skeleton muscle. METHODS: Thirty-two muscle samples were
      obtained from the vastus lateralis muscle of 7 subjects. These specimens were
      divided into three groups based on form of treatment: HS (n = 13), non HS (n =
      14), and control group (n = 5). The control group was performed under identical
      conditions without H2O2. Specimens in the HS group were incubated at 42 degrees C
      for 20 min, while those in the non-HS and control groups were maintained at 37
      degrees C. RESULTS: The control group showed no significant change in contractile
      force. Although contractile force significantly decreased 30 min after H2O2
      administration in both the HS and non-HS groups, only the HS group showed
      apparent recovery of contractile force 60 min after H2O2 administration. Lipid
      peroxidation was lower in the HS group than in the non-HS group. Ultrastructural
      examination revealed less mitochondrial damage in the HS group compared with the
      non-HS group. CONCLUSION: We found that human skeleton muscle escaped cellular
      damage induced by H2O2 in the early phase after heat stress. These data suggest
      evidence for an early effect of heat stress against ischemia/reperfusion injury
      in human muscle.

PMID- 9926194
TI  - Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled
      hypotension.
AB  - BACKGROUND: In our animal study, it was revealed that diadenosine tetraphosphate
      (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in
      mean arterial pressure compared to control value. Furthermore, in healthy male
      volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who
      require surgical procedures under general anesthesia together with controlled
      hypotension, hypotension was induced by Ap4A in order to examine its hypotensive
      effect and modulating action on the blood pressure. METHODS: Ten patients who
      required controlled hypotension and who were scheduled for elective surgery under
      general anesthesia were studied. Anesthesia was maintained with isoflurane (n =
      7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was
      induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose
      was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood
      pressure was achieved. Arterial blood pressure and heart rate were monitored.
      Arterial samples were drawn at 4 separate time points to measure the
      concentration of Ap4A in the plasma. RESULTS: The time required for attaining the
      target blood pressure after initiation of Ap4A infusion was about 16 min, and the
      time lapse between withdrawal of infusion to recovery of blood pressure was about
      18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound
      hypertension was evident after withdrawal. The plasma Ap4A concentration
      increased in response to the acceleration rate of Ap4A administration with a
      tendency of augmented hypotensive effect. CONCLUSION: As it produces an excellent
      hypotensive effect together with a modulating action on blood pressure, Ap4A was
      assessed as useful in producing controlled hypotension.

PMID- 9926195
TI  - Effects of adenosine infusion on gastric emptying in healthy volunteers.
AB  - BACKGROUND: A low dose of systemic adenosine infusion has been shown to induce
      antinociception in clinical experimental studies as well as in patients. There is
      no clinical information about the effect of adenosine on the motility of the
      gastrointestinal tract. The aim of this study was therefore to evaluate the
      effect of exogenous adenosine administration on gastric emptying in man. METHOD:
      Ten healthy male volunteers (22-45 yrs) were included in a placebo-controlled,
      double-blind, randomised, cross-over study, where the experiments were separated
      by at least one week. During one session the volunteers received a continuous
      intravenous infusion of adenosine (50 micrograms.kg-1.min-1) initiated 15 min
      prior to the test of gastric emptying (a standard test meal, followed by oral
      acetaminophen, 2 g) and lasting throughout the experiment (2 h). During the other
      experimental session an infusion of saline was given. Acetaminophen absorption
      test was used as an indirect measure of the rate of gastric emptying. Venous
      acetaminophen concentration curves were produced and the maximum acetaminophen
      concentration (Cmax), the time to reach the maximum concentration (Tmax), and the
      area under the serum acetaminophen concentration time curve from 0 to 60 min
      (AUC60) were calculated. RESULTS: There was no difference between placebo and
      adenosine in Cmax (197 vs. 199 mumol.L-1, P = 0.80), Tmax (23 vs. 45 min, P =
      0.14), AUC60 (9633 vs. 9111 min.mumol.L-1, P = 0.28). CONCLUSION: The results
      demonstrate that adenosine in a clinically antinociceptive dose of 50
      micrograms.kg-1.min-1 does not affect the rate of gastric emptying in healthy
      volunteers.

PMID- 9926196
TI  - The direct effect of halothane on myocardial contraction in rat myocytes with
      poorly developed gap junctional intercellular communication.
AB  - BACKGROUND: The gap junction channel plays an important role in synchronous
      beating in the heart, and the reduction in the amount of gap junctional
      intercellular communication (GJIC) is thought to be the main arrhythmogenic
      factor in diseased heart. However, the effect of halothane on myocardial
      contraction in heart tissue with less GJIC is not well known. The purpose of the
      present study is to examine the direct effect of halothane on myocardium with
      poorly expressed GJIC. METHODS: Ventricular myocytes were obtained from neonatal
      rats by enzymatic digestion with collagenase and then cultured for 3 or 7 d. We
      have previously reported that the number of gap junctions at 3 d is approximately
      10% of that at 7 d (1). The myocytes were stabilized in serum-free medium, and
      the spontaneous beating rate and amplitude were measured by a fiberoptic sensor.
      RESULTS: Heptanol (2 mM), an inhibitor of GJIC, abolished synchronized beating in
      myocytes cultured for 7 d. Halothane decreased the beating rate and amplitude in
      both groups of myocytes in a concentration-dependent manner (P < 0.05). Halothane
      at 1 and 2 MAC (adult rat MAC) decreased the beating rate more in myocytes
      cultured for 3 d than in myocytes cultured for 7 d (P < 0.05). Halothane reduced
      beating amplitude equally in both groups. Asynchronous contraction developed more
      frequently among myocytes cultured for 3 d than for those at 7 d. CONCLUSION:
      Halothane may block the GJIC channels, and when the number of these channels is
      reduced, exposure to halothane may cause asynchronous beating and decrease the
      beating rate. However, the halothane-induced decrease in amplitude is probably
      not due to blockade of GJIC because reducing the number of GJIC channels did not
      alter halothane's depressant effect.

PMID- 9926197
TI  - Finland's first anaesthesia revealed by newspapers.
AB  - BACKGROUND: According to the literature on the history of anaesthesia, Finland's
      first anaesthesia was given on March 8, 1847 for a ligature of an aneurysm of the
      subclavian artery. It has, however, not been possible to verify the date with
      certainty. We therefore wanted to find out whether newspapers might give
      additional information and how this exceptionally important medical invention had
      been received by the Finnish newspapers. METHODS: Microfilms of the 10 newspapers
      which appeared in Finland in 1847 were studied at the Helsinki University
      library. RESULTS: The first report which made reference to English newspapers was
      published on February 10 by "Borga Tidning". On March 6, "Helsingfors Tidningar"
      wrote that two anaesthesias had already been given in Helsinki; the first of them
      for a difficult varicose veins operation and the second for an exarticulation of
      a shoulder. But there was no information regarding the dates of the operations.
      Fortunately, both operations had been recorded in the patient diary of the
      clinic, although without any information about the anaesthesia. According to the
      diary, Johan August Orn was operated for varicose veins on February 16 and Anders
      Gustaf Henrikson had his right arm exarticulated on March 3. Both patients
      recovered. In total, only six pieces of news on anaesthesia were found.
      CONCLUSIONS: Finland's first anaesthesia was given on February 16, 1847, which is
      three weeks earlier than had been previously assumed.

PMID- 9926198
TI  - Angiotropic large B-cell lymphoma misdiagnosed as urosepsis with multiple organ
      dysfunction syndrome.
AB  - A 53-year-old woman with a history of cervical carcinoma 14 years ago, treated
      with hysterectomy and radiation therapy, was admitted to the intensive care unit
      with severe SIRS (systemic inflammatory response syndrome) progressing to shock,
      multiple organ failure and death within 5 d. Bilateral hydronephrosis diagnosed
      by sonography and an enlarged left kidney with suspected abscesses verified in a
      CT-scan suggested the diagnosis of urosepsis. However, multiple microbiological
      examinations remained sterile. Despite surgical treatment and aggressive
      intensive care, she died in unresponsive shock. Pathohistologically, an
      angiotropic large B-cell lymphoma, a rare diffuse intravascular neoplasm of
      lymphoid origin, was diagnosed. The patient's history of abdominal radiation
      therapy 14 years earlier as well as multiple negative microbiological specimens
      in a patient with suspected urosepsis should have initiated the search for a non
      infectious cause of the disease.

PMID- 9926199
TI  - Airway obstruction due to arytenoid prolapse in a child.
AB  - In paediatric patients, obstruction of the upper airway is still a common problem
      during general anaesthesia. This case report documents the susceptibility of
      arytenoids to prolapse in paediatric patients during halothane anaesthesia. The
      use of video endoscopy provides an excellent tool for visualizing this type of
      airway obstruction; and continuous positive airway pressure is an effective
      treatment for clearing the airway.

PMID- 9926200
TI  - Malignant hyperthermia and neuroleptic malignant syndrome in a patient during
      treatment for acute asthma.
AB  - Acute asthma is well known to provoke complications. We report the case of a
      patient who needed intubation and mechanical ventilation for acute asthma.
      Despite a treatment with corticosteroids, bronchodilators, neuromuscular blocking
      drugs and magnesium sulfate, the situation remained uncontrolled and as a last
      resort, halothane became necessary. The patient then developed an episode of
      malignant hyperthermia with fever at 40 degrees C and rhabdomyolysis. At this
      time, halothane could be stopped and all the symptoms disappeared without
      modifying the rest of the treatment. Eight days later, he presented with a
      neuroleptic malignant syndrome following an injection of droperidol. Temperature
      rose to 42 degrees C, associated with muscle rigidity, sweating, tachycardia and
      severe circulatory collapse. The use of dantrolene in association with a
      symptomatic treatment of the collapse led to a favourable outcome in.
      Unfortunately, in vitro contracture test could not be performed in this case. The
      links between malignant hyperthermia and neuroleptic malignant syndrome remain
      unclear. Although these two pathologies share the same physiopathology,
      symptomatology and treatment, they are clearly individualized. This case seems to
      be the first description of their occurrence in the same patient.

PMID- 9926201
TI  - Signs of massive intraoperative pulmonary embolism with extensive invasive
      monitoring.
AB  - A 71-year-old patient suffered a massive pulmonary tumor embolism during removal
      of a renal carcinoma. He had extensive invasive monitoring, and the data were
      stored for later analysis. This shows that most of the known signs of pulmonary
      embolism were present in the tracings. It is discussed how none of them alone was
      sufficient for clinical diagnosis, but the comparison of several simultaneous
      variables together may be of great help. This report shows also the importance of
      the data-storing devices in the anesthesia monitors to make these comparisons
      possible in quickly changing emergency situations.

PMID- 9926202
TI  - Another cause for transient radicular pain.

PMID- 9926203
TI  - Anaesthesia for a patient on interferon therapy.

PMID- 9926204
TI  - Editorial on LMWH and regional anaesthesia--dangerous recommendations.

PMID- 9926205
TI  - Biliary sludge: a well defined sonographic entity.
AB  - OBJECTIVES: Identify the present of biliary sludge (BS) in our patients, since
      different authors have concluded that this entity may be an etiologic agent of
      biliary colic, gallbladder stones and some complications such as acute
      pancreatitis and acalculous cholecystitis. METHODS: We reviewed retrospectively
      the abdominal sonographic reports of 2802 patients of our gastroenterologic unit,
      with an average age of 40.5 years. The variables of the protocol were:
      gallbladder stones, BS and acute and chronic gallbladder inflammation. RESULTS:
      Considering the mentioned criteria, we entered to the study 2682 patients, 17.8%
      (n = 479) had lithiasis, 13.2% (n = 356) had BS, 2% (n = 54) had acute
      gallbladder inflammation and 2.3% (n = 64) had chronic gallbladder inflammation.
      Of the group of patients with BS 42.7% (n = 152) were female and 57.3% (n = 204)
      were males. 52% of the patients with BS were between the ages of 26 to 45 years.
      CONCLUSIONS: In our study we found an important prevalence of BS that was over
      13% which is higher than the results reported by additional series. Its early
      sonographic detection, follow-up, removal of precipitating factors and treatment
      are all adequate measures in order to achieve its elimination.

PMID- 9926206
TI  - [Anal incontinence: proposal of an evaluation score].
AB  - Anal incontinence is a shameful disease in which degree of severity must be
      assessed to design a suitable treatment and to be able to quantly the degree of
      relief or cure of this ailment. Therefore we have set a score table on basis of:
      physical features of the leakage (gas, liquid or solid) relating it to the
      frequency (daily, weekly or monthly) (10 to 20 points), during night time, daily
      light or both (1 to 3 points), hability to perceive the leakage (1 to 2 points),
      diapers needed (0 to 1 point), social or work limitations (0 to 2 points) (see
      table N. 1). Adding point, 4 degrees of severity are determinated: 1. light (type
      1): less then 5 points, 2. moderate (type 2): 6 to 10 points, 3. moderately
      severe (type 3): 11 to 15 points, 4. quite severe (type 4): 16 to 20 points,
      Comparing the score of the patient before and after treatment we shall be able to
      know whether he has cured, just relieved, or whether there been no response.

PMID- 9926207
TI  - [Helicobacter pylori detection by polymerase chain reaction in gastric juice and
      its correlation with the histology (Giemsa)].
AB  - HP infection is involved in the pathogenesis of several gastroduodenal diseases,
      as type B chronic gastritis, duodenal and gastric ulcer, MALT lymphoma and
      gastric cancer. The recent availability of molecular techniques, specifically the
      PCR, allow us to detect very low amounts of the bacterium. The aim of the study
      is to evaluate the presence of HP in gastric juice by PCR technique and to
      correlate this findings with histology (Giemsa) of gastric mucosa. Gastric juice
      PCR positive findings were found in 10/31 (32.3%) HP positive patients at
      histology. We concluded that HP in gastric juice is possible to detect by
      molecular techniques. In our study 32.3% of the patients showed the presence of
      HP in gastric juice.

PMID- 9926208
TI  - [Computed tomography of acute primary epiploic appendicitis].
AB  - Primary epiploic appendicitis is a rare but well known intraabdominal
      inflammatory process that characteristically presents with an onset of symptoms
      similar to diverticulitis, appendicitis and other abdominopelvic processes. CT
      findings are pathognomonic, consistent with a pericolonic oval shaped area of
      increased density with peritoneal thickening, and fat stranding. The condition is
      self limited and resolves completely within days under non-steroid
      antiinflammatory therapy.

PMID- 9926209
TI  - [Polypoid hyperplasia of Brunner's glands].
AB  - The case of an eighty five year old woman with a polypoid hyperplasia of
      Brunner's glands as cause of digestive tract hemorrhage is reported.

PMID- 9926211
TI  - [Biliary sludge].

PMID- 9926210
TI  - [Are there "good" H. pylori and "bad" H. pylori?/].

PMID- 9926212
TI  - Preparing and developing faculty through faculty development initiatives.

PMID- 9926213
TI  - Career transition from clinician to academician: responsibilities and
      reflections.
AB  - Being an educator is just as much an art and a science as is being a clinician.
      This article describes the faculty role and its basic responsibilities for
      occupational therapy practitioners who are considering the transition to academic
      educator positions. The faculty role has unique characteristics. Differentiating
      therapy activities from academic activities is an essential part of a career
      transition from clinician to academician. This article also describes the various
      features of the academic context and its impact on individual performance, how to
      assess readiness for the faculty role, and the typical application process.

PMID- 9926214
TI  - Developing the instructional skills of new faculty members in occupational
      therapy.
AB  - During the past 5 years, the American Occupational Therapy Association, American
      Occupational Therapy Foundation, and Medical University of South Carolina worked
      together to promote the instructional performance of new faculty members within
      the profession. This article describes the development and progression of
      initiatives for more than 300 new faculty members in occupational therapy and the
      characteristics of those who participated. On the basis of experience gained with
      these new faculty members, we recommend that the profession of occupational
      therapy adopt a more systematic approach to conceptualizing, planning, and
      orchestrating the range of faculty development activities needed by academicians;
      develop strategies to socialize and encourage prospective faculty members to
      develop the necessary academic qualifications sooner in their careers; and
      explore ways in which experienced academicians from other fields can be enticed
      into our own to strengthen existing faculties.

PMID- 9926216
TI  - Cooperative learning as an approach to pedagogy.
AB  - Lecture-based pedagogical approaches cannot adequately prepare students in
      professional and technical occupational therapy programs. Faculty members in
      other disciplines are turning to a well-known and well-researched teaching
      approach called cooperative learning, which is more carefully structured and
      defined than most other forms of small group learning. Cooperative learning
      includes several key principles: positive interdependence, individual
      responsibility, appropriate grouping, group maintenance, cooperative skills, and
      promotive (interaction) time. This article provides ideas for managing the
      classroom with cooperative learning activities and describes eight of them: Three
      Step Interview, Roundtable, Think-Pair-Share, Structured Problem Solving,
      Send/Pass-a-Problem, Generic Question Stems, Double Entry Journal, and Dyadic
      Essay Confrontation. Each activity is applied to content embedded in professional
      and technical occupational therapy curricula. A cooperative learning approach to
      evaluating learning is also presented.

PMID- 9926215
TI  - Academic Juggling Act: beginning and sustaining an academic career.
AB  - Rapid expansion in the number and size of occupational therapy academic programs
      has resulted in a crucial need for faculty recruitment and retention. To
      encourage occupational therapy practitioners to consider academia as a career
      option, and to support those who choose this option, this article reviews higher
      education literature related to socialization into academia, the different types
      of academic institutions, the tenure system, and the process of entering into and
      sustaining an academic career. This literature is then correlated with issues in
      occupational therapy education. The article closes with specific literature-based
      suggestions for creating and sustaining an academic career through development of
      teaching skills, research agendas, and support systems.

PMID- 9926217
TI  - Educational interpretation of "cooperative learning as an approach to pedagogy".

PMID- 9926218
TI  - Developing a research career: advice from occupational therapy researchers.
AB  - OBJECTIVE: Occupational therapy faculty members often need guidance in developing
      a research program that will result in publication and sponsorship. This
      qualitative study investigated how university faculty members had successfully
      established research programs. METHOD: Nine well-known occupational therapy
      researchers were interviewed by telephone regarding how they had established a
      research career. These interviews were transcribed and analyzed. RESULTS: The
      advice of the occupational therapy researchers included the following: complete a
      doctoral education, find mentors, and link with colleagues who have similar
      research interests. They also recommended that new researchers learn to take
      risks and accept criticism, prioritize, manage work time, and learn about the
      systems that support research. CONCLUSION: Occupational therapy researchers'
      experiences can be used to provide helpful advice and guidance for faculty
      members who are beginning research programs.

PMID- 9926219
TI  - Teaching portfolios: an effective strategy for faculty development in
      occupational therapy.
AB  - The special challenge of the occupational therapy practitioner embracing the role
      of faculty member is discovering a formative process of continual improvement
      that will also serve as an authentic assessment of teaching and learning within
      the particular disciplinary boundaries of occupational therapy. Although other
      means achieve such complex aims, the teaching portfolio is a powerful tool for
      fostering reflective practice and for creating an ongoing record of substantial
      evidence. A teaching portfolio is an evidence-based written document in which a
      faculty member, working in collaboration with a mentor, concisely organizes
      selective details of teaching accomplishment and effort and uses such information
      to document his or her teaching enterprise. More importantly, the faculty member
      uses the information for reflective analysis, leading to improvement of teaching
      and student learning. The emphasis on reflection, analysis, evidence, and
      mentoring suggests that the teaching portfolio can set the stage for meaningful
      collaboration in a system of evaluation that is based appropriately on recorded
      evidence of improvement and demonstrated positive outcomes of student learning.

PMID- 9926220
TI  - Issues in developing a faculty evaluation system.
AB  - The increasing demands for accountability in higher education are resulting in
      calls for important personnel decisions--such as promotion, tenure, pay, and
      continuation--to be based directly on the outcomes of systematic faculty
      evaluations. This article provides a step-by-step procedure for developing a fair
      and meaningful faculty evaluation system on which such personnel decisions can be
      based. The procedure systematically involves faculty and administrators in the
      design and development of a faculty evaluation program that reflects the unique
      values, priorities, and heritage of an institution. The resultant faculty
      evaluation system integrates data from students, peers, and administrators to
      provide meaningful evaluative information for both faculty use in self
      improvement efforts and administrative use in making personnel decisions that are
      based on a valid and reliable faculty performance record.

PMID- 9926221
TI  - A historical cross-disciplinary perspective on the professional doctorate in
      occupational therapy.
AB  - Clinical doctorates are emerging in occupational therapy. By examining the
      development of clinical doctorates in medicine, dentistry, psychology, pharmacy,
      nursing, and physical therapy, implications can be drawn for the future of
      occupational therapy education. These histories offer us a sense of the distinct
      purpose and curricular structure of the professional doctorate, its successes and
      problems, its general sequence of unfolding, the political dynamics surrounding
      it, and the potential it holds for supporting the profession's capacity for
      service to patients.

PMID- 9926222
TI  - Are faculty prepared to address ethical issues in education?

PMID- 9926223
TI  - Resource list for teaching and learning.

PMID- 9926224
TI  - The use of Rasch analysis to produce scale-free measurement of functional
      ability.
AB  - Innovative applications of Rasch analysis can lead to solutions for traditional
      measurement problems and can produce new assessment applications in occupational
      therapy and health care practice. First, Rasch analysis is a mechanism that
      translates scores across similar functional ability assessments, thus enabling
      the comparison of functional ability outcomes measured by different instruments.
      This will allow for the meaningful tracking of functional ability outcomes across
      the continuum of care. Second, once the item-difficulty order of an instrument or
      item bank is established by Rasch analysis, computerized adaptive testing can be
      used to target items to the patient's ability level, reducing assessment length
      by as much as one half. More importantly, Rasch analysis can provide the
      foundation for "equiprecise" measurement or the potential to have precise
      measurement across all levels of functional ability. The use of Rasch analysis to
      create scale-free measurement of functional ability demonstrates how this
      methodlogy can be used in practical applications of clinical and outcome
      assessment.

PMID- 9926227
TI  - What will it take for more occupational therapists to become case managers?
      Implications for education, practice, and policy.

PMID- 9926226
TI  - Alleviating gender role strain in adult men with traumatic brain injury: an
      evaluation of a set of guidelines for occupational therapy.
AB  - OBJECTIVE: A set of guidelines to assist men with traumatic brain injury (TBI) to
      alleviate gender role strain was assessed to determine its effectiveness and
      acceptability to participants. METHOD: Four adult male participants with TBI
      received the intervention (the set of guidelines) for 4 months. The intervention
      consisted of rebuilding self-identified gendered social roles and activities.
      Focused interviews and participant observation were used to determine whether
      gender role strain changed after intervention. RESULTS: The participants reported
      that the intervention enabled them to (a) enhance their gender role satisfaction
      through newly rebuilt roles and activities, (b) attain certain long-held personal
      goals, (c) feel more like members of society, (d) perceive a greater congruency
      between their internal self-images and external postinjury roles, (e) learn more
      about personal skills and values as men, (f) feel more comfortable using help
      seeking behaviors, (g) feel a sense of shared experience and affinity, (h) feel
      more understood and accepted, and (i) contribute to others through community
      member roles. DISCUSSION: The set of guidelines for alleviating gender role
      strain was effective in assisting these participants to enhance their gender role
      satisfaction through rebuilding desired male-gendered social roles and
      activities. Dating, courtship, extended family member, community member, friend,
      and mentor-protege roles, lost as a result of TBI, were rebuilt through gender
      neutral activities that facilitated a sense of volitional control, competency,
      and normalcy. Nonetheless, the men continued to lack desired rites of passage
      leading from male adolescence to adulthood.

PMID- 9926225
TI  - Occupations and well-being: a study of personal projects.
AB  - OBJECTIVE: The purpose of this study was to explore the relationship between
      occupation and subjective well-being (SWB). METHOD: A convenience sample of 120
      adults completed a personal projects analysis, a method of rating their current
      goal-directed pursuits. They also completed measures of SWB (Affect Balance
      Scale, Life Satisfaction Index Form A) and personality traits (Myers-Briggs
      Personality Inventory). Characteristics of personal projects were correlated with
      SWB scores. Multiple regression analysis was used to investigate possible
      predictors of well-being from among the characteristics of personal projects,
      personality traits, and demographic variables. RESULTS: The stress associated
      with personal projects was significantly and inversely correlated with well
      being, as was project difficulty. Perceived progress in completing projects was
      significantly positively correlated with well-being. The strongest predictors for
      well-being were the composite project factors of stress and efficacy. Two
      personality traits, sensing and extraversion, interacted with the project
      dimension of stress to emerge as significant predictors of well-being. Together,
      these four variables explained 42% of the variance in well-being scores.
      CONCLUSION: These findings are consistent with assumptions that attributes of
      meaningful occupations are significantly related to people's perceived well
      being.

PMID- 9926228
TI  - Bringing a top-down approach to pediatrics.

PMID- 9926229
TI  - Take action on efficacy studies.

PMID- 9926230
TI  - An overview of the Fourth International Symposium on Hodgkin's Disease. Recent
      advances in basic and clinical research.

PMID- 9926231
TI  - Epstein-Barr virus in Hodgkin's disease.
AB  - Epstein-Barr virus (EBV), a B-lymphotropic herpesvirus widespread in human
      populations, is carried by most individuals as an asymptomatic lifelong
      infection. Much progress has been made in our understanding of virus
      infection/persistence, and in the role of the cytotoxic T lymphocyte response in
      control of that infection. This same virus is linked to several malignancies,
      including endemic Burkitt's lymphoma, post-transplant lymphoproliferative disease
      and to many cases of Hodgkin's disease (HD). Recent evidence showing that HD,
      like the other EBV-associated lymphomas, is of B-cell origin suggests that the
      pathogenesis of these malignancies may share more common ground than previously
      thought. The biology and cytotoxic T-cell control of primary and persistent EBV
      infection, and the links between EBV and all three lymphomas are reviewed. The
      expression of viral antigens in EBV-positive HD raises the possibility of
      developing tumour immunotherapy, using relevant components of the EBV-specific T
      cell response; progress to date, and future prospects for immune control of EBV
      positive HD are discussed.

PMID- 9926232
TI  - Clonality and germinal centre B-cell derivation of Hodgkin/Reed-Sternberg cells
      in Hodgkin's disease.
AB  - Molecular single-cell studies of Hodgkin and Reed-Sternberg (HRS) cells in
      Hodgkin's disease (HD) have revealed the clonal nature of these peculiar tumour
      cells. HRS cells in classical HD as well as lymphocyte predominant (LP) HD
      originate from germinal center (GC) B cells in most cases, if not all. Whereas
      HRS cells in LP HD represent transformed antigen-selected GC B cells with
      evidence of ongoing immunoglobulin (Ig) V gene mutation, HRS cells in classical
      HD appear to often or always derive from GC B cells that have lost the capacity
      to express a functional antigen receptor. Using Ig gene rearrangements amplified
      from HRS cells as clonal markers for the tumour cells, it could be shown that the
      same HRS cell clone can disseminate in the patient and persist throughout the
      course of the disease. A common derivation of the tumour cells was recently
      demonstrated in two cases representing combinations of HD and non-Hodgkin's
      lymphoma. Finally, V-gene analysis showed that viable cells enriched by magnetic
      cell sorting from HD patients as HRS cells indeed represent the HRS-cell
      population of the patient.

PMID- 9926233
TI  - Immune escape mechanisms in Hodgkin's disease.
AB  - BACKGROUND: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's
      disease are histologically characterised by a small population of neoplastic
      cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS
      cells) and an extensive admixture of other cell types including lymphocytes,
      plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is
      largely known, but the mechanisms and functional effects are not. The small
      lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that
      express early activation markers. The absence of prominent specific cytotoxic T
      cell or natural killer (NK) cell populations seems to argue against a Th1-type
      response, whereas the sometimes prominent admixture of plasma cells and
      eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell
      population may result from selective influx of CD4 T cells or from selective
      depletion of CD8 and NK cells. RESULTS AND DISCUSSION: The T cells surrounding RS
      cells have an immuno-phenotype and cytokine production capability consistent with
      a Th2-type response. RS cells express several members of the TNF receptor family
      such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS
      expressing, CD8+ T cells and NK cells. The RS cells also produce TGF beta and
      interleukin-10 that may downmodulate the Th1 response. In addition, the Reed
      Sternberg cells produce the chemokine TARC that could lead to the specific
      attraction of a Th2 T-cell subset. CONCLUSION: RS cells have several mechanisms
      that may allow it to escape an effective immune response. The relative
      contributions of each of these and other potential mechanisms are not yet known.

PMID- 9926234
TI  - World Health Organization Classification of lymphomas: a work in progress.
AB  - The World Health Organization (WHO) publishes classification handbooks for all
      neoplastic diseases. The last WHO Classification of leukemias and lymphomas was
      published in 1976. Since that time, through cytogenetics and molecular biology,
      it has been shown that many hematopoietic neoplasms are associated with a unique
      genetic profile. Similarly, the development of widely available and routinely
      applied monoclonal antibodies has allowed the identification of a unique
      immunophenotypic profile for most leukemias and lymphomas. These techniques have
      permitted the recognition of a number of distinct disease entities, and also
      enhance both diagnostic accuracy and reproducibility. The WHO Classification has
      been developed under the joint auspices of the European Association for
      Hematopathology (EAHP) and the Society for Hematopathology (SH). First organized
      in 1995, the Steering Committee appointed 10 committees covering T-cell and B
      cell lymphomas and leukemias, myeloid and histiocytic tumors. The committees were
      asked to develop a list of diseases within their topic area, and to establish
      definitions of each disease according to established criteria. The WHO
      Classification uses the principles of the R.E.A.L. Classification, which defines
      each disease according to its morphology, immunophenotype, genetic features,
      postulated normal counterpart, and clinical features. Morphologic and clinical
      variants of individual diseases are discussed in the text, and their use is
      optional. The proposed classification was presented at the USCAP meeting in 1997,
      the site of the first joint meeting of the EAHP and SH. The presentation was
      followed by an open forum attended by EAHP and SH members. The Steering Committee
      also appointed a Clinical Advisory Committee to ensure that the classification
      meets clinical needs, and to resolve questions of clinical significance. The
      proposed WHO Classification for lymphomas is similar to the R.E.A.L.
      Classification for lymphomas, with minor modifications and reassessment of
      provisional categories based on new data since 1994.

PMID- 9926235
TI  - Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma).
AB  - Despite advances in immunohistochemistry and molecular biology, the distinction
      between classical Hodgkin's lymphoma and related diseases such as nodular
      lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or
      anaplastic large cell lymphoma has remained difficult in rare cases. Lack of
      clear-cut diagnostic criteria represents a problem for both the pathologist and
      the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma
      and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of
      such cases, 12 expert hematopathologists each submitted one to five borderline
      cases to a workshop. Cases were reviewed and classified at a multiheaded
      microscope and criteria were established for the diagnosis of questionable cases.
      Well established entities such as classical Hodgkin's lymphoma, anaplastic large
      cell lymphoma and TCRBCL were defined more strictly and cases with unusual
      morphology or antigen expression could be identified. A distinctive subset of
      cases representing mediastinal large B-cell lymphomas with features of Hodgkin's
      lymphoma was identified.

PMID- 9926236
TI  - Lymphocyte predominant Hodgkin's disease: pathology and clinical implication.
AB  - The special nature and course of lymphocyte rich variants of Hodgkin's disease
      (HD) has been the subject of pathological and clinical studies since the 1930s.
      Patients with lymphocyte predominant (LP) HD, predominantly male and 25-45 years
      old, usually present with early clinical stage, cervical or inguinal involvement
      and few if any adverse prognostic factors. The disease progresses slowly, with
      fairly frequent relapses which are rarely fatal. Nonetheless, cases with advanced
      stage and deaths from Hodgkin's disease have been observed in LPHD. Recently,
      immunological studies have lead to a clear distinction between LPHD and classical
      HD including a lymphocyte rich classical version (LRCHD). Secondary low-grade
      NHLs occur more frequently after LPHD than after classical HD. They seem to be
      disease-related rather than treatment-induced. LPHD patients in earlier studies
      have tended to have a better prognosis than classical HD patients. When cohorts
      of the same clinical stage are compared, under modern protocol treatment this
      advantage seems to be minimal or absent. LPHD patients tend to relapse frequently
      but they survive these relapses better than classical HD patients. The
      resemblance to non-neoplastic disorders, capability for ongoing mutation,
      favorable clinical presentation and good survival rates after relapse all suggest
      that the optimal primary treatment strategy might be less intensive for LPHD than
      for classical HD. Late toxicities, which contribute considerably to the death
      rate, could thus be reduced. The long survival of several early stage LPHD
      patients without any treatment beyond lymph node excision could favour a 'watch
      and-wait' strategy, albeit only after rigorous staging. New experimental therapy
      techniques such as immunotherapy might also be suitable. These possibilities must
      first be tested in a large-scale prospective study.

PMID- 9926238
TI  - The role of radiotherapy for early stage Hodgkin's disease: limitations and
      perspectives.
AB  - For limited stage Hodgkin's disease (HD), the role of radiotherapy has been
      changing during the last decades, the main point being the (almost) complete
      disappearance of irradiation used alone. Actually, exclusive radiotherapy yielded
      satisfactory results in terms of long-term survival, but in 1998, it was becoming
      impossible not to take into account the late overmortality observed in all large
      cohorts of HD patients. This overmortality has been shown to be related (1) to
      cardiac toxicity of irradiation and (2) to secondary radiation-induced solid
      tumors. So the search for new strategies, as efficient, but less toxic, could not
      be avoided any more. For surgically staged patients (pathological stages I and
      II), irradiation alone (i.e., mantle field radiotherapy) can still be proposed to
      patients without unfavourable prognostic factors after a negative surgical infra
      diaphragmatic exploration. For clinically staged patients with limited disease
      and favourable prognostic indicators, the association of chemotherapy and
      radiotherapy appears more and more as a standard. In parallel, efforts are being
      made to alleviate the therapeutic burden. For radiotherapy, previous experience
      showed that, after a chemotherapy-induced complete remission, irradiation of the
      initially involved areas only was enough treatment. Ongoing trials are now
      exploring the possibility of a dose desescalation from the conventional 36 Gy to
      20 Gy (as for children HD), and maybe to ... 0 Gy (no radiotherapy at all).
      Desescalation in the number of chemotherapy cycles is also being investigated.
      For clinically staged patients with unfavourable prognostic indicators, a higher
      percentage of cases still appears to be refractory to treatment. So, while chemo
      radiotherapy clearly became the standard strategy, efforts are essentially being
      devoted to identify new--and hopefully more efficient--chemotherapy schemes. In
      parallel, irradiation dose desescalation is being investigated. Most of these
      pending questions are addressed in a number of ongoing trials, as well in the US
      as in Europe, with the aim of offering to patients treatments at least as
      efficient as the presently used schedules, and less toxic in the long term.

PMID- 9926237
TI  - The many faces of Hodgkin's disease around the world: what have we learned from
      its pathology?
AB  - In the past decade there have been many advances in our understanding of
      Hodgkin's disease. Among the most important is the discovery that the Reed
      Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal,
      and thus a true lymphoma, deserving of a name change, to 'Hodgkin's lymphoma'
      (HL). Based on a combination of immunophenotype and morphology, the R.E.A.L.
      Classification recognizes two main types of HL: classical types (nodular
      sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte
      depletion) and nodular lymphocyte predominance type (NLPHL), which probably
      represent distinct biological entities. The immunophenotype and genetic features
      of both classical HL and NLPHL have been defined. These are useful in the
      subclassification of HL and in distinguishing HL from two recently-described,
      aggressive lymphomas that were in the past often diagnosed as HL: anaplastic
      large-cell lymphoma, T-cell type (ALCL), and T-cell/histiocyte-rich large B-cell
      lymphoma (T/HRBCL). Epstein-Barr virus has been detected in approximately 40% of
      the cases of classical HL, and is clonal, suggesting that this virus may play a
      role in the pathogenesis of at least some types of HL. The frequency of HL varies
      in different populations, and the frequency of EBV-positive HL appears to be
      inversely related to the overall frequency of HL in a given population. Thus, it
      is possible that its presence may simply reflect the prevalence of EBV-infected B
      cells in the individual. Despite the advances of the past ten years, many
      questions remain to be answered, and these will provide the challenges of the
      next decade.

PMID- 9926239
TI  - Radiotherapy in early stage Hodgkin's disease: principles and results of recent
      clinical trials.
AB  - For decades, radiotherapy has been used as a single treatment modality for early
      stage Hodgkin's disease. In recent years, late radiation effects, such as
      myocardial infarctions and induced solid tumours, have become of major concern.
      It now seems clear that chemotherapy coupled with radiotherapy not only improves
      relapse-free survival, but can also replace radiotherapy as adjuvant treatment
      for subclinical disease. This offers the opportunity of reduction of extended
      fields and high doses, which hopefully correlates with lower late radiation
      toxicity. The challenge for clinical trials on the treatment of early stages
      Hodgkin's disease in the coming years will be the trade-off between adjuvant
      radiotherapy and adjuvant chemotherapy, reducing radiotherapy in volume and dose
      without jeopardising the 90% overall survival that can be achieved nowadays.

PMID- 9926241
TI  - Model based development of the BEACOPP regimen for advanced stage Hodgkin's
      disease. German Hodgkin's Lymphoma Study Group.
AB  - In this article we summarize the theoretical arguments which led us in the German
      Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a
      large randomised trial to investigate the role of moderate dose escalation in the
      treatment of advanced stage Hodgkin's disease. Although some indications for a
      role of dose were available in the early 1990s no prospective randomised trial
      had been undertaken. In order to obtain an impression of the shape of the
      essential dose response characteristic we developed a novel statistical model
      that could be used to analyse a set of data in which dose variations had
      occurred. The model took tumour growth and chemotherapy effects into account. The
      model could be applied to clinical data on tumour control and treatment given in
      a patient population. The model was fitted to the data of 706 patients which had
      received COPP/ABVD-like regimens. It revealed considerable heterogeneity in
      chemosensitivity and a positive slope of the doseresponse relationship. The model
      was used to simulate the effect of various treatment strategies with dose
      escalation and schedule changes. On the basis of such simulations we predicted
      that shortening cycle intervals from 4 to 3 weeks should lead to small benefits
      (about 3% in five-year tumour control rates). In contrast, we predicted that a
      moderate average dose escalation by 30% of a standard chemotherapy would lead to
      a potential benefit in the order of 10%-15% in tumour control at five years.
      Subsequently we searched for a treatment scheme that would permit such a dose
      escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic
      substances (cyclophsphamide, adriamycin and etoposide) to be given in the
      beginning of a cycle. These three substances were then subject to dose escalation
      in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic
      effects. The dose level found feasible for a large multicentre setting turned out
      to be in the required magnitude. The HD9 trial of the GHSG was then initiated to
      examine whether the predicted dose response curve really exists.

PMID- 9926240
TI  - BEACOPP: a new regimen for advanced Hodgkin's disease. German Hodgkin's Lymphoma
      Study Group.
AB  - The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a
      rearranged schedule permitting a shortened three-week cycle. With haematological
      growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin
      could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment
      1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard
      COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any,
      due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by
      local irradiation. The most recent interim analysis, with 689 evaluable patients,
      circa 40% of all expected events and a median observation time of 27 months,
      showed significant differences in progression rate (P) and in two-year freedom
      from treatment failure (F) between the treatment arms, with escalated BEACOPP (P
      = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than
      COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute
      toxicity was more severe due to dose escalation, but remained manageable. These
      preliminary results suggest that BEACOPP improves efficacy. Moderate dose
      escalation is feasible with G-CSF support and appears likely to make a worthwhile
      improvement in the cure rate. The results must await confirmation (or otherwise)
      by the final analysis including all randomised patients and sufficiently mature
      data.

PMID- 9926242
TI  - Current clinical trials for the treatment of adult Hodgkin's disease: common
      strategies and perspectives.
AB  - Strategies in the treatment of adult Hodgkin's disease (HD) are changing
      strikingly in current clinical trials. In early as well as in intermediate stage
      HD a common aim of most study groups now is the reduction of radiation dose and
      volume in order to minimize severe late effects like myocardial damage and
      secondary neoplasias. As a consequence extended field irradiation is abandoned in
      nearly all trials, and combined modality treatment will be used not only in
      intermediate, but also in early stage HD. In advanced stage HD new chemotherapy
      regimens, based on the principle of a moderate dose escalation, for the first
      time seem to improve the therapeutic outcome. Thus, the priority in current
      clinical trials for advanced stage HD is the long-term evaluation of these new
      regimens with regard to treatment efficacy and toxicity.

PMID- 9926243
TI  - The case for and against high-dose therapy with stem cell rescue for early poor
      prognosis Hodgkin's disease in first remission.
AB  - After 10 years we are still not clear whether dose escalation with stem cell
      transplantation is relevant for some patients with poor prognosis Hodgkin's
      disease in first remission. Some of the problems relating to the controversy
      relate to the fact that the definition of high risk Hodgkin's disease in terms of
      prognostic factors is only now in 1998 being delineated properly. It is also
      possible that some of the dose escalation in lymphoma has taken place without an
      adequate amount of conventional therapy beforehand. It may be possible that dose
      escalation should be added to an adequate amount of conventional chemotherapy not
      integrated in a conventional regimen thus shortening it. Newer studies from the
      German Hodgkin's Disease Study Group, i.e. HD9, may be suggesting that
      conventional chemotherapy is producing good results in poor prognosis patients
      and thus negating the need for dose escalation and stem cell transplantation.

PMID- 9926245
TI  - Treatment of relapsed Hodgkin's disease: strategies and prognostic factors.
AB  - The major points in salvage therapy of patients in relapse following combination
      chemotherapy for advanced disease are: (1) success of any second-line approach is
      determined by prognostic factors which include age, duration of the initial
      remission, and quantity of disease at relapse; (2) induction failures
      (progression without remission or incomplete remission and short initial
      remission) require innovative therapy which currently entails high-dose
      chemotherapy with peripheral or bone marrow autologous support; (3) late relapse
      still retains an order to sensitivity to chemotherapy and can be treated with
      conventional dose combination with complementary radiation therapy to previously
      unirradiated bulky sites. The choice of regimen is empiric and can include a
      repeat of the regimen used for the original remission or induction. The relative
      advantage of HDC in this favorable group is uncertain.

PMID- 9926244
TI  - Radiation therapy as a component of high-dose salvage strategies in Hodgkin's
      disease.
AB  - The expected event-free survival for patients undergoing high-dose salvage
      therapy for Hodgkin's disease is 40%-60%. Three-quarters of these patients will
      relapse in prior sites of disease. Radiation therapy is a very effective local
      regional modality in Hodgkin's disease. It is possible that the judicious use of
      radiation can improve the event-free survival of high-dose salvage programs.
      Retrospective analysis supports this concept, but the rationale should be
      incorporated and tested in prospective clinical trials.

PMID- 9926246
TI  - Primary refractory Hodgkin's disease.
AB  - Primary refractory Hodgkin's disease may generally be defined as progression of
      disease during induction treatment or a partial or transient response (< 60 days)
      to induction therapy. Salvage chemotherapy is inadequate in this patient
      population; fewer than 10% of patients survive for 10 years or longer. Improved
      outcomes after failure of primary induction therapy have been reported with
      myeloablative therapy and autografting. The projected event-free survivals ranged
      from 18%-49% at four years. Highly selected patients may benefit from salvage
      radiotherapy, but this may be best accomplished in combination with
      transplantation. A number of strategies might be considered for increasing the
      cure rate for the small subset of patients with primary refractory Hodgkin's
      disease. Among these, identification of patients at high risk for induction
      failure and modifications of primary treatment to address this risk hold the
      greatest promise for success.

PMID- 9926248
TI  - Rare syndromes in Hodgkin's disease.
AB  - The presentation of Hodgkin's disease is in the vast majority of cases rather
      classical. However, there are some rare syndromes which might be very puzzling.
      In this contribution, we will discuss some of these rare syndromes. We will
      concentrate on following topics: (1) pruritus (itching), (2) cutaneous
      manifestations of HD, (3) alcohol-related pain, (4) nephrotic syndrome, (5)
      hemolytic anemia, (6) idiopathic thrombocytopenia purpura (UTP), (7) ivory
      vertebrae, and (8) CNS involvement.

PMID- 9926249
TI  - Pediatric Hodgkin's disease: treatment in the late 1990s.
AB  - BACKGROUND: For two decades now combined chemo-radiotherapy has been preferred in
      most of the studies on childhood Hodgkin's disease (HD), because combined
      modality is the precondition for (1) reducing the radiation dose, (2) reducing
      the radiation fields, (3) shortening chemotherapy, (4) omitting splenectomy and
      laparotomy, and thus, for optimizing the benefit/risk ratio between cure rates
      and late effects. Recently, the rationale for this approach was strengthened by
      worrisome data about the increasing incidence of secondary breast cancer in women
      treated for HD in childhood, adolescence or adult age < 30 years. Nearly all
      breast cancers were localized in the former radiation field, and the relative
      risk was much higher after doses > 40 Gy than after lower doses. These findings
      suggest that pediatric therapy approaches abandoning radiotherapy alone with its
      high doses and large fields should be extended to adolescents treated outside of
      pediatric studies and to adults younger than 30. The risk of chemotherapy-related
      secondary leukemias can be limited to < 1% by omitting mechlorethamine and
      restricting the cumulative doses of other drugs with leukemogenic potential, as
      demonstrated by the experience with ABVD and the recently published data of the
      German-Austrian pediatric group. PATIENTS AND METHODS: The updated results of the
      German-Austrian multicenter study HD-90 are presented in this paper (578 patients
      < 18 years, follow-up: median 4 years, maximum 7 years). Patients were allocated
      to three treatment groups (TG) according to disease stage. In all three TG,
      induction procarbazine, prednisone, adriamycin) for girls and two cycles of OEPA
      (etoposide instead of procarbazine) for boys. Patients of TG 2 and 3 additionally
      received two or four cycles of COPP (C, cyclophosphamide), respectively. CT was
      followed by radiotherapy to the involved sites (reduced fields if possible) of
      25, 25 and 20 Gy in the 3 TG, respectively. PRELIMINARY RESULTS: For the total
      group of 578 pats, overall survival (OS) at 5 years is 98% and event-free
      survival (EFS) 91%. In TG 1, EFS for girls (2 OPPA) is 96%, and for boys (OEPA),
      94%, in TG 2 and 3 (combined), 92% and 86%, respectively. Secondary leukemias
      were not observed so far, thirty-one male patients of TG 1 who were tested
      endocrinologically showed normal FSH levels. CONCLUSIONS: The especially high
      efficacy of OPPA and OPPA/COPP could be confirmed in study HD-90 with reduced
      radiation doses and fields. OEPA and OEPA/COPP CT also produced very favorable
      results, not significantly different from those with OPPA and OPPA/COPP. It may
      be anticipated that the ratio between cure rates and risks of late effects of
      study HD-90 will compare favorably to approaches of other groups. It would be
      useful for the future continued optimization of HD therapy to attain a rough
      consensus at an international level about principles which should be considered
      for pediatric approaches. Some proposals have been made for treatment of early
      stages.

PMID- 9926247
TI  - New drugs in the treatment of Hodgkin's disease.
AB  - In the treatment of Hodgkin's disease (HD) remission rates of 80% have been
      achieved with combination regimens such as COPP/ABVD; 30%-50% of these patients
      relapse, however, and less than 25% of those in first relapse can be cured.
      Although 90% of adults with advanced Hodgkin's disease (HD) achieve a complete
      remission with new polychemotherapy regimens such as BEACOPP, it is too early to
      assess how many patients ultimately can be cured. In addition, these regimens are
      associated with severe side effects including infertility, cardiomyopathy or
      second malignancies. Thus, alternative strategies for improving the outcome of
      patients with HD have been developed. These approaches include new cytostatic
      drugs and biological agents. Here, we review the most recent developments
      including the new vinca alkaloid vinorelbine, the anthracycline idarubicin, the
      nitrogen mustard bendamustine, the recently developed nucleoside analogue
      gemcitabine, and immunotoxins against Hodgkin/Reed-Sternberg cells. We conclude
      that current polychemotherapy regimens could possibly be improved by introducing
      new agents with a different mechanism of action such as gemcitabine. In addition,
      some of these new drugs including gemcitabine or vinorelbine could contribute to
      the reduction of toxic side effects, thus resulting in an improved quality of
      life for patients with HD.

PMID- 9926250
TI  - Treatment of grey zone lymphomas.
AB  - The inability of distinguishing difficult cases of Hodgkin's disease from non
      Hodgkin's lymphoma has been a long-standing problem. Initially, the controversy
      centered on lymphocyte-depleted Hodgkin's disease; now with improved diagnostic
      techniques, most controversy centers around the anaplastic large-cell lymphomas.
      These problematic cases may also represent a less frequent problem, although data
      on this point is difficult to obtain. The future controversy may well involve the
      separation of T-cell rich B-cell lymphoma and Hodgkin's disease, nodular
      paragranuloma type. Fortunately, to date the clinical data does not support that
      there is a major difference in therapeutic results depending on whether these
      cases are treated as Hodgkin's disease or non-Hodgkin's lymphoma.

PMID- 9926251
TI  - Molecular basis of targeted chemotherapy: novel concepts with special reference
      to the treatment of Hodgkin's disease.
AB  - Concepts for the treatment of Hodgkin's lymphomas based on novel insights of the
      molecular mechanisms responsible for the maintenance of the transformed phenotype
      of Reed-Sternberg cells, their proliferation and sensitivity to radiation and
      anti-tumor agents are discussed. The potentials of some recently developed new
      signal transduction inhibitors for the treatment of Hodgkin's lymphomas are
      discussed in greater detail and comprise agents directed against Janus kinase 2
      (JAK 2); Signal Transducers and Activators of Transcription (STAT factors);
      agents directed against SH 2-domains: the fes/fps oncogene, Ras; protein kinase C
      (PKC) isotypes and means of inducing radiation or drug-induced apoptosis.

PMID- 9926252
TI  - Treatment of relapsed Hodgkin's disease using EBV-specific cytotoxic T cells.
AB  - Donor-derived Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) are
      successful in the prevention and treatment of Epstein-Barr virus (EBV)-associated
      lymphoproliferative disease (LPD) in allogeneic bone marrow transplant (BMT)
      recipients [1, 2]. This finding prompted us to use a similar approach to the
      treatment of relapsed EBV-positive Hodgkin's disease [3]. Autologous EBV-specific
      CTL lines could be generated on the first or second attempt from 11 of 15
      patients with Hodgkin's disease. Peripheral blood TCR zeta-chain levels were low,
      but increased in the activated CTL lines. Three patients have received gene
      marked autologous CTL. The first two patients experienced alleviation of stage B
      symptoms and a drop in peripheral blood EBV load. However, this situation
      reversed between 6 and 12 weeks after infusion, when chemotherapy and radiation
      were reinstated. Both patients eventually progressed and died. The third patient
      had a pleural effusion, which increased after CTL infusion. Analysis of the
      pleural effusion revealed both tumor cells and levels of marker gene over 100
      fold greater than in peripheral blood. The infused CTL line showed activity
      against LMP2. The patient initially improved and then remained stable for over
      eight months after CTL infusion, but now has progressive disease. We currently
      are evaluating methods for introducing the LMP2 gene into dendritic cells and
      using these to present LMP2 to autologous T cells. Using both retrovirus and
      herpesvirus vectors to express LMP2 in dendritic cells, LMP2-specific CTL were
      successfully generated from individuals who were EBV-seronegative or who were non
      responsive to LMP2 when presented on autologous LCL. In future protocols, LMP2
      specific CTL will be used for treatment.

PMID- 9926253
TI  - Long-term toxicity of the treatment of Hodgkin's disease.
AB  - At the present time, the majority of patients who develop Hodgkin's disease can
      be cured with radiotherapy and/or chemotherapy. A long follow up of cured
      patients has shown that the cumulative toxicity from treatment related
      complication rivals the mortality from Hodgkin's disease. In addition to late
      fatal complications, delayed adverse effects of therapy on the thyroid,
      reproductive system, and bones are burdens many patients have to bear. Future
      treatment regimens for Hodgkin's disease will be designed attempting to minimize
      these complications. Follow up of those patients now in remission should focus on
      the prevention of morbidity and mortality by anticipating and preventing late
      complications.

PMID- 9926254
TI  - Hodgkin's disease: quality of life in future trials.
AB  - It is of great importance to collect data of objective as well as subjective
      morbidity in patients cured for Hodgkin's disease. Such information may be used
      when new treatment strategies are discussed, in patients information and
      communication, to establish rehabilitation programs and to identify individuals
      who may benefit from rehabilitation. Measurement of health related quality of
      life (HRQOL) may give important information on how the cancer and/or the
      treatment has influenced the patients. There is no gold standard instrument for
      measurement of HRQOL in cancer. However, it is a consensus to use
      multidimensional patients rated measures with a standard format and scoring
      procedure. SF-36, EORTC QLQ-C30 and FACT are widely used in Europe and North
      America. Domain specific instruments includes a more comprehensive evaluation of
      a specific domain, for example anxiety or fatigue. Fatigue seems to be a
      prevalent symptom in Hodgkin's disease survivors and might affect patients'
      ability to perform normal activities and will often reduce their quality of life.
      Fatigue is defined as a subjective feeling of tiredness and might be measured by
      standardised and validated instruments such as the Fatigue Questionnaire (FQ) and
      the Multi-Dimensional Fatigue Inventory (MFI-20). Clinical significance might be
      defined as a meaningful difference based on consensus by the patient, the doctor
      and the society. In oncology there is no agreement of how long a meaningful
      difference in survival should be. For HRQOL a difference between 7 to 10 on a
      scale ranking from 0 to 100 has been regarded as clinical significant by some
      researchers. Another strategy to approach the issue of clinical significance is
      to use norms-estimates from the normal population- and/or reference estimates as
      guidelines. The long-term complication of the successful treatment of Hodgkin's
      disease reinforced the need for continued surveillance of treatment and related
      morbidities. Fatigue is a prevalent symptom and detailed diagnostic work-up is
      essential to identify patients with this problem. More knowledge about possible
      biological causes is required in order to understand fatigue and the impact on
      quality of life among Hodgkin's disease survivors.

PMID- 9926255
TI  - Quality of life assessment in Hodgkin's disease: a new comprehensive approach.
      First experiences from the EORTC/GELA and GHSG trials. EORTC Lymphoma Cooperative
      Group. Groupe D'Etude des Lymphomes de L'Adulte and German Hodgkin Study Group.
AB  - Previous reports from available trials have dealt with negative long-term
      sequelae in Hodgkin's disease (HD) survivors. There is, however, a lack of
      longitudinal data showing the correlation between outcome and various treatment
      related variables and the process of re-adaptation into normal life after the end
      of treatment. In order to investigate the quality of life (QoL) of patients with
      HD in different dimensions during active treatment and follow-up and to identify
      longitudinal patterns of QoL dimensions during re-adaptation to normal life
      within the EORTC Lymphoma Cooperative Group and Groupe D'Etude des Lymphomes de
      L'Adulte (EORTC/GELA) and the German Hodgkin Study Group (GHSG), QoL assessment
      strategies were put into use over the last three to five years. Furthermore, the
      efforts aimed at obtaining cross-cultural comparisons between the participating
      countries and study groups (EORTC/GELA and GHSG). Within the randomised
      EORTC/GELA Trial 'H8' for clinical stage I-II HD which started in September 1993,
      patients receive a QoL questionnaire for completion at each follow-up visit
      during the first 10 years after the end of active therapy. The corresponding
      'HD8' study of the GHSG employs the assessment of QoL during and after active
      treatment periods. Within both studies, the EORTC QLQ C30 is used for QoL
      assessment incorporated in the QLQ-S (quality of life questionnaire for
      survivors), which additionally addresses the aspects of fatigue/malaise,
      sexuality, specific side effects, and retrospective evaluation of treatment. In
      total the QLQ-S includes 45 questions on 14 functional, symptom, and fatigue
      scales, 15 additional single items, and 3 open questions. In addition to the
      longitudinal QoL assessment, the GHSG carried out cross-sectional QoL trials with
      all cured surviving patients from the past HD1-6 studies and a matched normal
      control sample employing the QLQ-S and the life situation questionnaire (LSQ), an
      instrument covering objective data from 45 domains of life. To date, within the
      trials H8 and HD8 over 3000 QoL questionnaires from more than 800 patients from
      ten countries are available for analysis. Replication of the psychometric
      properties of the scales revealed satisfactory results using factor analyses and
      reliability testing across languages for the QLQ-S. A feasibility analysis showed
      generally a good acceptance of the questionnaire by the patients and physicians.
      QoL assessment within international multicentre trials in HD proved feasible
      within the two differently organised study groups of EORTC/GELA and GHSG. The use
      of subjective QoL data (QLQ-S) together with objective data (LSQ) in a combined
      cross-sectional and longitudinal trial system will give the most comprehensive
      insight into the problems of the re-integration process into normal life after
      cure. This information will provide the basis for the development of
      remedies/help measures and possible modifications of treatment strategies. The
      current approach will be further developed in close collaboration between both
      trial groups, and next steps will include translation of the LSQ into other
      languages and adaptation to various cultural circumstances.

PMID- 9926256
TI  - Estimation of Young's modulus in swine cortical bone using quantitative computed
      tomography.
AB  - The cortical bones of swine were cut into plates measuring 40 x 10 x 2 mm and
      scanned by quantitative computed tomography (QCT). Compressive loading tests were
      performed at 100 Newtons, and the strain on the bone was measured with strain
      gauges. The mean Young's modulus and Poisson's ratio of one hundred specimens
      were 19.4 +/- 5.8 GPa and 0.34 +/- 0.09, respectively. A positive correlation (r
      = 0.47 +/- 0.11, p < 0.001) was observed between Young's modulus and the bone
      density of specimens determined by QCT, which suggests that QCT values might
      directly predict Young's modulus of cortical bone.

PMID- 9926257
TI  - Synovial immunohistochemical changes after high tibial osteotomy for
      osteoarthritis of the knee. Two-year prospective follow-up.
AB  - The synovium of the osteoarthritic knee was investigated for pathological changes
      after high tibial osteotomy (HTO) in a prospective two-year follow-up study. The
      series included 11 osteoarthritic knees in 9 patients with a mean age of 57 +/- 8
      years (range: 47 to 70 years). Synovial specimens were obtained from the medial
      part of the knee just above the medial meniscus at the time of HTO, and taken
      from a different medial portion from the initial biopsy at the time of removal of
      the internal fixation (mean interval: 21 +/- 4 months). Lining cell hyperplasia,
      villous hypertrophy, cell infiltration, and vascular proliferation, observed in
      the first biopsy specimens, were less discernible in the samples from the second
      biopsy, which were obtained at the time of the removal of the fixation device.
      Immunohistochemical staining of the specimens revealed that cartilage fragments
      positive for type 2 collagen were surrounded by proliferating lining cells at the
      time of osteotomy. These lining cells were predominantly stained with anti-CD68
      antibody for macrophage lineage cells. The mean numbers of type 2 collagen
      positive fragments and CD68-positive cells in the lining layer at HTO were 9.1 +/
      6.2 (3 to 26) and 30.8 +/- 11.0 (17 to 55) per high power field (x400),
      respectively, while they were 1.1 +/- 1.2 (0 to 4) (p < 0.005) and 14.8 +/- 4.7
      (7 to 21) (p < 0.01), respectively, at the time of removal. The number of these
      cartilage fragments decreased markedly after correction of the varus deformity by
      HTO. In conclusion, the excessive pressure on the medial compartment of the
      osteoarthritic knee with a varus deformity can cause wearing of the articular
      cartilage and fragmentation. The cartilage fragments might stimulate macrophage
      lineage cells in the lining layer and might cause synovitis in osteoarthritis.
      After correction of the varus deformity by HTO, the synovitis subsided because
      there were fewer cartilage fragments and less wear.

PMID- 9926258
TI  - The function of posterior tilt of the tibial component following posterior
      cruciate ligament-retaining total knee arthroplasty.
AB  - To increase the range of motion in the knee, posterior cruciate ligament
      retaining total knee arthroplasty (TKA), which has a roll back (RB) mechanism, is
      used. The roll back mechanism is the complex movement of the femoral condyles
      relative to the tibial plateau, which results in translation of the tibiofemoral
      contact point posteriorly as the knee is flexed. This study was undertaken to
      assess the function of the posterior cruciate ligament (PCL) and posterior tibial
      tilt following PCL-retaining TKA. Eleven fresh-frozen cadaveric normal lower
      extremity specimens (average age: 75.4 years; range: 69 to 88 years) were
      obtained for this study. The test was performed on a loading frame after specimen
      preparation. The calcaneal bone was fixed on the rigid frame. A load of 9.5 kg
      was applied perpendicularly by the moving frame to femoral head through four
      casters. PCL strain and RB were measured before and following TKA by changing the
      posterior tilt of tibial component and the external rotation of femoral
      component. PCL strain at 105 degrees flexion in the 0 degree posterior tilt group
      (3.3% +/- 2.4%) was decreased in the 10 degrees posterior tilt group (0.6% +/-
      0.5%), and this decrease was statistically significant (p < 0.05). RB was
      measured as anterior-posterior translation by using an arthroscopic probe. After
      TKA, RB was decreased in the medial compartment but was increased in the lateral
      component. These different movements of the tibiofemoral contact points
      consequently caused rotation in the flexion position. Posterior tilt of the
      tibial component decreased the efficiency of the PCL's function. Retaining the
      PCL physically is not the same as preserving the function of the PCL because of
      the lack of the ACL, the change of the joint line, the differences in articular
      geometry, and the balance of the ligaments.

PMID- 9926259
TI  - A new technique for morphologic measurement of the femur. Its application for
      Japanese patients with osteoarthrosis of the hip.
AB  - The cementless femoral prostheses developed in Western countries have commonly
      been used for Japanese patients, but it has been noted that it is difficult to
      achieve a good fit between the cementless femoral prostheses and some femora. In
      Japan, there are many patients with secondary osteoarthrosis (OA) of the hip, but
      Western designed femoral prostheses seem to be mainly for use with primary OA of
      the hip. To design femoral prostheses better suited to Japanese patients, a new
      method to study the morphometry of the femur is required--one which can determine
      the particular features of the femur in Japanese patients. In this study, a new
      morphologic measurement technique of the femur is proposed and applied to a
      number of Japanese OA patients in order to demonstrate its efficacy. In this
      technique, a three-dimensional solid model based on the outer and inner borders
      of the femoral cortex is constructed from 3-D CT images and computer-aided design
      (CAD) software. The bone axis is defined as the line of best fit to the centers
      of gravity of the femur cross sections in each CT plane by using the least square
      method. A new femur coordinate system is considered based on this bone axis. The
      corrected outer borders of the cortex are reconstructed in sections perpendicular
      to the bone axis. The angle between the principal axis of inertia of the sections
      and a plane defined by the femur coordinate system is selected as providing a
      good measurement of the torsion value to characterize the femur morphology. The
      angles of principal axis were measured in 110 OA and 36 normal hips, and then
      compared with each other. A significant difference between the OA and normal
      group was observed especially in the proximal region above the section 6 mm below
      the level of the lesser trochanter. It is suggested that the anteversion of the
      femoral neck influences the torsion of the parts below the lesser trochanter.
      From the results, it is demonstrated that the proposed measurement technique is a
      reliable and efficient means of determining femur morphology.

PMID- 9926260
TI  - Strain on the gastrocnemii and hamstrings affecting standing balance on an
      inclined plane in spastic cerebral palsy. A study using a geometric model.
AB  - The purpose of this study was to use an non-invasive method to determine whether
      strain on the gastrocnemii and hamstrings influences postural balance in spastic
      cerebral palsy (CP). Changes in alignment during standing posture with subjects
      positioned on a platform that was gradually inclined were measured in 10 normal
      children and 11 children with CP. The changes in postural alignment were plotted
      and geometric models used to determine the lines where the gastrocnemii and
      hamstrings were maximally stretched. In this way the relationship between
      postural alignment and the amount of strain on the gastrocnemii and hamstrings
      was investigated. On the inclined platform, which caused ankle joints to become
      dorsiflexed as the inclination angle increased, the gastrocnemii began to be
      strained and the hip joints began to be flexed (trunk bent forward) at the same
      time. In the children with CP, the gastrocnemii were more strained by smaller
      degrees of inclination. Furthermore, there was one child with CP whose hamstrings
      were also strained on the inclined platform. We confirmed that postural balance
      was affected by strain on the gastrocnemii and hamstrings.

PMID- 9926261
TI  - Glenohumeral osteoarthritis following a "color test" during rotator cuff repair.
      A case report and a review of the literature.
AB  - A case of glenohumeral osteoarthritis in a 35-year-old female following a color
      test during rotator cuff repair is described. The patients had a tear in the
      rotator cuff involving the supraspinatus muscle and rotator interval. A color
      test with a 0.4% aqueous solution of gentian violet was performed during the
      operation and the ruptured cuff was not tightly sutured. The patient developed
      glenohumeral osteoarthritis 25 months postoperatively. Plain film radiographs
      showed joint space narrowing and bone sclerosis of the humeral head, but there
      was no evidence of osteophytes. This pathology was thought to have been caused by
      the aqueous gentian violet solution.

PMID- 9926262
TI  - An important drug interaction.

PMID- 9926264
TI  - Patients' diets and preferences in a pediatric population with inflammatory bowel
      disease.
AB  - PURPOSE: To determine the dietary practices of the pediatric inflammatory bowel
      disease population at the Children's Hospital of the Hamilton Health Sciences
      Corporation and the reported effectiveness of those diets. PATIENTS AND METHODS:
      A questionnaire mailed to 153 pediatric patients was returned by 125 patients (76
      Crohn's disease [CD] and 49 ulcerative colitis [UC] patients)--an 82% response
      rate. RESULTS: The median age of respondents was 13 years, and 62% were male.
      Ninety per cent and 71% of CD and UC patients, respectively, had changed their
      diets since diagnosis. Caloric supplements (eg, BOOST [Mead Johnson
      Nutritionals]), sole source nutrition, low fibre and lactose-free diets were used
      by more than 15% of CD patients, whereas lactose-free, nonspicy, low acid,
      additive-free, caloric supplement and low fibre diets were used by more than 15%
      of UC patients. A diet supplement was more commonly used in CD patients (P <
      0.05) and an additive-free diet in UC patients. Corn and corn products, nuts,
      milk and bran were avoided by more than 20% of CD and UC patients; however, more
      CD than UC patients avoided corn and corn products. In addition, UC patients
      (more than 20%) also avoided tomato, other dairy (nonfluid milk-based products
      and foods containing milk products), chocolate, cheese, wheat, tomato sauces and
      fruit juice. A benefit was reported for 103 of 141 reported diets, with the most
      commonly alleviated symptoms being abdominal pain, diarrhea and flatulence.
      CONCLUSION: Many children with inflammatory bowel disease have altered their
      diets to manage their disease and have attributed symptomatic relief to these
      diets.

PMID- 9926265
TI  - The Second Canadian Gastroesophageal Reflux Disease Consensus: moving forward to
      new concepts.
AB  - Gastroesophageal reflux disease (GERD) is a disease with serious consequences
      that may result in significant impairment in quality of life and disease
      morbidity. Across all grades of severity of symptoms and severity of underlying
      esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over
      prokinetics (PKs) or H2 receptor antagonists (H2RAs). The potential cost
      effectiveness of using medications with higher acquisition costs that may lower
      health care costs overall is often disregarded when conducting cost comparisons
      with medications having lower 'up-front' costs. Limiting therapy to less
      effective agents condemns many patients to protracted suffering, repeated
      physician visits and needless reinvestigation of symptoms that could have been
      resolved by appropriate initial therapy. Based on current data, use of any
      classification of symptom severity as a basis for selecting one class of
      therapeutic agents over another for first line therapy (i.e. PKs, H2RAs for
      'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.

PMID- 9926263
TI  - Beta-blockers.

PMID- 9926266
TI  - Neutrophil-mediated gastrointestinal injury.
AB  - Inflammatory diseases of the gastrointestinal tract are frequently characterized
      by a dense infiltration of neutrophils in the lamina propria and the subsequent
      transepithelial migration of these cells into the lumen. While the neutrophil
      plays an essential role in defending against bacterial infection, it can also
      cause significant injury to the host tissue. The evidence for a role of
      neutrophils in producing significant tissue injury in a number of
      gastrointestinal disorders and the mechanisms through which neutrophils produce
      tissue injury are reviewed. Furthermore, the evidence that some commonly used
      anti-inflammatory drugs produce beneficial effects through modulation of
      neutrophil extravasation or activation is reviewed.

PMID- 9926267
TI  - Intriguing gastrointestinal properties of bismuth: a folk remedy brought into the
      realm of clinical and investigative medicine.

PMID- 9926268
TI  - Mucinous cystadenoma of the appendix in a patient with systemic lupus
      erythematosus.
AB  - A 38-year-old female with systemic lupus erythematosus presented with abdominal
      pain, diarrhea and iron-deficient anemia. Computed tomogram showed a 2 x 4 cm
      inhomogeneous lesion of the right adnexa. An unusual mass was identified
      extending from the appendiceal orifice at colonoscopy, and an 8 cm tubular
      appendix, apparently prolapsed into the cecum, was identified at celiotomy. An
      appendectomy with cecectomy was performed. On cut section, mucin was extruded
      from the lumen of the appendix. A mucinous neoplasm of the appendix with mucinous
      dissection to the serosal surface was reported at the time of frozen section. No
      gross ovarian pathology or peritoneal implants were noted. Cystadenoma with
      associated mucocele formation was verified by permanent histology. Mucocele of
      the vermiform appendix is a rare condition associated with neoplastic
      transformation in approximately 75% of all cases. Benign mucinous cystadenoma of
      the appendix should be differentiated from cystadenocarcinoma by frozen section
      at the time of celiotomy to ensure appropriate treatment. While systemic lupus
      erythematosus can lead to cutaneous mucinosis, an association with mucinous
      cystadenoma of the appendix has not been previously reported. Surveillance for
      metachronous colonic neoplasms is warranted in patients diagnosed with a mucinous
      neoplasm of the appendix.

PMID- 9926271
TI  - alpha-Tocopherol in atherogenesis: do we know its real role?

PMID- 9926272
TI  - Principles of combination therapy for hypertension: what we learn from the HOT
      and other studies--a personal point of view.
AB  - With the publication of the HOT study, the desirable diastolic blood pressure in
      hypertensives has dropped to between 80 and 85 mmHg. To achieve such low levels
      requires combination therapy in the majority. Combination therapy is set to
      become standard practice in the management of hypertension, so that it is now
      appropriate to consider the principles involved.

PMID- 9926273
TI  - Gallopamil activity on asynergic viable myocardium in acute myocardial
      infarction: insights on stunned and hibernating myocardium.
AB  - The influence of the calcium antagonist gallopamil on the contractility of
      asynergic viable myocardium after acute myocardial infarction treated with
      thrombolysis was investigated by two-dimensional echocardiography. Sixteen
      patients with > or = 1 viable segment(s), identified during the low-dose phase
      (up to 10 micrograms/kg/min) of a dobutamine echocardiographic test (up to 40
      micrograms/kg/min) performed 4-5 days after a first acute myocardial infarction,
      were given a gallopamil intravenous bolus (50 micrograms/kg) 12-24 hours later.
      Two-dimensional echocardiography was done before and 15 minutes after the bolus.
      A score index of 1 (normokinesis) to 4 (dyskinesis) and a 16-segment model were
      used. A segment was considered viable when a resting asynergy (score > or = 2)
      improvement of > or = 1 grade was seen during low-dose dobutamine. Follow-up
      echocardiograms were done 3-5 months later. A total of 30 viable segments were
      found; of these, 10 showed sustained improvement in contractility (group A)
      during high-dose dobutamine, while 20 exhibited a biphasic response returning to
      their basal contractile state (group B). After the gallopamil bolus, 9 of 10
      group A segments improved their contractility, in comparison with 0 of 20 group B
      segments (P < .001). Infarct-related vessel significant (> or = 75%) coronary
      stenosis was present in the tributary vessel of 0 of 10 group A and of 20 of 20
      group B segments (P < .001). At follow-up, 9 of 10 group A segments showed a
      spontaneous contractile improvement; of the 20 group B segments, 8 of 10 that
      underwent revascularization (7 angioplasty, 3 bypass graft) showed contractile
      improvement, in comparison with 0 of 10 segments not revascularized (P = .001).
      We conclude that gallopamil may reverse the contractile dysfunction of
      postischemic stunned myocardium in patients with acute myocardial infarction,
      whereas no effects are apparent on ischemic/hibernating myocardium.

PMID- 9926274
TI  - Evaluation of the effect on heart rate variability of some agents acting at the
      beta-adrenoceptor using nonlinear scatterplot and sequence methods.
AB  - There is evidence that the processes regulating heart rate variability (HRV)
      reflect nonlinear complexity and show "chaotic" determinism. Data analyses using
      nonlinear methods may therefore reveal patterns not apparent with the standard
      methods for HRV analysis. We have consequently used two nonlinear methods, the
      Poincare plot (scatterplot) and cardiac sequence (quadrant) analysis, in addition
      to the standard time-domain summary statistics, during a normal volunteer
      investigation of the effects on HRV of some agents acting at the cardiac beta
      adrenoceptor. Under double-blind and randomized conditions (Latin square design),
      25 normal volunteers received placebo, salbutamol 8 mg (beta 2-adrenoceptor
      partial agonist), pindolol 10 mg (beta 2-adrenoceptor partial agonist), or
      atenolol 50 mg (beta 1-adrenoceptor antagonist). Single oral doses of medication
      (at weekly intervals) were administered at 22:30 hours, with sleeping heart rates
      recorded overnight. The long-term (SDNN, SDANN) and short-term (rMSSD) time
      domain summary statistics were reduced by salbutamol 8 mg and increased by
      atenolol 50 mg compared with placebo. The reductions in both SDNN and SDANN were
      greater after salbutamol 8 mg compared with pindolol 10 mg. The reduced HRV after
      pindolol 10 mg differed from the increased HRV following atenolol 50 mg. The
      Poincare plot, constructed by plotting each RR interval against the preceding RR
      interval, was measured using a reproducible computerized method. Scatterplot
      length and area were reduced by salbutamol 8 mg and increased by atenolol 50 mg
      compared with placebo; scatterplot length and area were lower after pindolol 10
      mg compared with atenolol 50 mg. Geometric analysis of the scatterplots allowed
      width assessment (i.e., dispersion) at fixed RR intervals. At the higher
      percentiles (i.e., 90% of scatterplot length: low HR), salbutamol 8 mg reduced
      and atenolol 50 mg increased dispersion; at lower percentiles (i.e., 10%, 25%,
      and 50% length), atenolol 50 mg and pindolol 10 mg increased dispersion compared
      with placebo and salbutamol 8 mg. Cardiac sequence analysis (differences between
      three adjacent beats; delta RR vs. delta RRn + 1) was used to assess the short
      term patterns of cardiac acceleration and deceleration. Four patterns were
      identified: +/+ (a lengthening sequencing), +/- or -/+ (balanced sequences), and
      finally -/- (a shortening sequence). Cardiac acceleration episodes (i.e., number
      of times delta RR and delta RRn + 1 were both changed) were increased in
      quadrants -/- and +/+ following pindolol 10 mg and salbutamol 8 mg; the beat-to
      beat difference (delta RRn + 1) was reduced after salbutamol 8 mg compared with
      the three other groups. These results demonstrated a shift towards sympathetic
      dominance (beta-adrenoceptor partial agonist salbutamol 8 mg) or parasympathetic
      dominance (beta 1-adrenoceptor antagonist atenolol 50 mg); pindolol 10 mg
      exhibited HR-dependent effects, reducing HRV at low but increasing variability at
      high prevailing heart rates. These nonlinear methods appear to be valuable tools
      to investigate HRV in health and to study the implications of perturbation of HRV
      with drug therapy in disease states.

PMID- 9926275
TI  - Combination of a calcium antagonist, verapamil, with an angiotensin converting
      enzyme inhibitor, trandolapril, in experimental myocardial ischemia and
      reperfusion: antiarrhythmic and hemodynamic effects of chronic oral pretreatment.
AB  - The combination of a calcium antagonist with an angiotensin-converting enzyme
      (ACE) inhibitor is increasingly used in the therapy of hypertension, but there
      are no experimental data supporting the use of this combination in acute
      myocardial ischemia and reperfusion. We tested the effects of oral pretreatment
      in a pig model, paying special attention to arrhythmias and adverse hemodynamic
      effects. Pigs received verapamil 240 mg + trandolapril 4 mg, verapamil 240 mg, or
      placebo orally once daily for 10 days, after which a coronary artery was ligated
      for 20 minutes and then allowed to reperfuse. The ventricular fibrillation
      threshold (VFT) was measured during ischemia to assess the vulnerability of the
      heart to ventricular fibrillation, whereas spontaneous tachyarrhythmias were
      monitored during reperfusion. Regional left ventricular (LV) blood flow was
      measured with radioactive microspheres. During the ischemic period, both the
      combination of verapamil plus trandolapril, and verapamil alone, prevented a fall
      in the VFT, indicating antiarrhythmic activity. The combination maintained LV
      contractile activity and cardiac output (CO) at preligation levels, whereas
      verapamil alone decreased cardiac output. During reperfusion, verapamil plus
      trandolapril prevented spontaneous ventricular tachyarrhythmias and increased
      blood flow in the reperfused zone. In contrast, verapamil was not antiarrhythmic
      and decreased CO. Thus the addition of the ACE inhibitor trandolapril to the
      calcium antagonist verapamil resulted in antiarrhythmic activity during ischemia
      and reperfusion, and produced a better hemodynamic profile.

PMID- 9926276
TI  - Short-term estrogen reduces myocardial infarct size in oophorectomized female
      rabbits in a dose-dependent manner.
AB  - 17 beta-estradiol, administered acutely, protects ischemic myocardium in male
      rabbits. In the present study we investigated the effect of short-term estrogen
      on myocardial infarct size in oophorectomized female rabbits. We oophorectomized
      24 sexually mature New Zealand white female rabbits. Twelve animals were left
      untreated and 12 received oral conjugated estrogens, 0.15 mg/day, for 4 weeks. At
      a second stage, a third group of 12 oophorectomized female rabbits was treated
      with intramuscular conjugated estrogens, 1 mg/day, also for 4 weeks. All rabbits
      underwent 30 minutes of coronary artery occlusion and 2 hours of reperfusion
      while on anesthesia with i.v. pentobarbital. Infarct and risk area were
      delineated by Zn-Cd fluorescent particles and tetrazolium chloride staining. The
      infarct size was expressed as a percentage of the risk zone (I/R %). Data are
      reported on 26 animals that survived the treatment period and the experiment.
      Heart rate, systolic, and mean blood pressure and double product did not differ
      between the three groups at baseline, ischemia, and reperfusion. The infarct size
      of the risk zone was significantly smaller in the intramuscular group compared
      with both the oral and the placebo group (18.5 +/- 3.5% vs. 41.3 +/- 9.2% and 43
      +/- 8.4%, respectively, P = 0.03). Conjugated estrogens, administered
      intramuscularly at a high dose, protect ischemic myocardium in oophorectomized
      female rabbits.

PMID- 9926277
TI  - Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator
      inhibitor-1 levels in patients with essential hypertension.
AB  - Increased sympathetic activity seems to play an important role in the
      pathogenesis and development of complications of atherosclerotic origin in
      patients with essential hypertension (EH). The aim of this study was to evaluate
      the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria
      (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue
      plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH
      associated with increased UAE. Fifty-eight patients (32 M, 26 F) with EH and
      microalbuminuria, with a mean age of 56.6 +/- 8.2 years and a body mass index
      (BMI) of 23.8 +/- 3.1 kg/m2 who responded to M therapy (0.3-0.4 mg/daily) were
      studied before and after their blood pressure control. The 24-hour urine albumin
      excretion (RIA method), as well as TM and PAI-1 plasma levels (ELISA method),
      were determined before and 6 months after the initiation of treatment under
      moxonidine therapy. At the end of the 6-month period, all patients remained
      normotensive. The 24-hour urine albumin excretion had decreased to 24.5 +/- 6.4
      vs. 32.3 +/- 7.2 ug/min before therapy (P < 0.001). The plasma TM levels had
      decreased to 44.0 +/- 7 vs. 51.0 +/- 9 ng/mL before therapy (P < 0.01), and PAI-1
      levels had also decreased to 11.5 +/- 4.5 vs. 15.8 +/- 8 IU/mL before therapy (P
      < 0.05). The results of our study suggest that in hypertensive patients with
      microalbuminuria, moxonidine, an imidazoline I1-receptor agonist, a new centrally
      acting antihypertensive agent, significantly reduces urine albumin excretion as
      well as thrombomodulin and PAI-1 levels. These preliminary findings demonstrate a
      favorable effect on renal function and endothelial homeostatic mechanisms
      (maintenance of haemostatic balance).

PMID- 9926278
TI  - Three-month effects of candesartan cilexetil, an angiotensin II type 1 (AT1)
      receptor antagonist, on left ventricular mass and hemodynamics in patients with
      essential hypertension.
AB  - Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated
      the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1)
      receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients
      with essential hypertension. Ten patients (four men and six women) with essential
      hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks.
      After drug administration, systolic blood pressure (BP) decreased from 178.9 +/-
      17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from
      101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and
      echocardiography revealed a significant decrease in LV mass index (LVMI) after
      candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2
      to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from
      123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular
      resistance decreased significantly during treatment with candesartan cilexetil in
      both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to
      1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8
      dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography.
      These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12
      weeks is beneficial in the regression of cardiac hypertrophy in patients with
      essential hypertension.

PMID- 9926279
TI  - Postrepolarization refractoriness as a potential anti-atrial fibrillation
      mechanism of pilsicainide, a pure sodium channel blocker with slow recovery
      kinetics.
AB  - The antifibrillatory effect of pilsicainide, a sodium channel blocker with slow
      recovery kinetics, was investigated in a canine model of atrial fibrillation.
      Prolonging the atrial effective refractory period is an important mechanism for
      pharmacological termination of atrial fibrillation. However, the effectiveness of
      potassium channel blockers has been questioned because of their reverse-use
      dependent property. In eight open-chest dogs, the duration of the atrial
      endocardial monophasic action potential and the atrial effective refractory
      period were determined using a Franz catheter. Conduction velocity was obtained
      from a 96-channel mapping electrode at multiple cycle lengths. Inducibility of
      sustained atrial fibrillation (> 30 minutes) was confirmed by atrial burst pacing
      during bilateral vagal stimulation, and local fibrillation cycle lengths were
      measured. Five minutes after restarting fibrillation, pilsicainide (0.6 mg/kg +
      0.04 mg/kg/min) was administered. After fibrillation was terminated, measurements
      were repeated. Pilsicainide successfully terminated atrial fibrillation in 7 of 8
      dogs after the median time of 5.1 minutes. The conduction velocity decreased
      significantly. Although pilsicainide did not affect monophasic action potential
      duration, it caused use-dependent prolongation of the atrial effective refractory
      period (P < 0.05), creating postrepolarization refractoriness. Accordingly,
      pilsicainide prolonged the atrial fibrillation cycle length from 80.6 to 113.8 ms
      (P < 0.05) before termination of fibrillation. Sodium channel blockers with slow
      recovery kinetics can prolong the atrial effective refractory period without
      affecting monophasic action potential duration. Unlike potassium channel
      blockers, these sodium channel blockers maintain postrepolarization
      refractoriness, even at rapid stimulation rates, thus exerting a salutary
      antifibrillatory effect.

PMID- 9926280
TI  - Effect of flecainide on heart rate variability in subjects without coronary
      artery disease or congestive heart failure.
AB  - Heart rate variability is a noninvasive indicator of autonomic nervous system
      activity. The role of the autonomic nervous system in the genesis of atrial or
      ventricular arrhythmias is now well established. Little is known about the
      effects of flecainide on heart rate variability in patients with normal heart
      structure, the main population receiving flecainide. This study was designed to
      evaluate the effects of flecainide on heart rate variability in patients without
      coronary artery disease or congestive heart failure. Time and frequency domain
      analysis of heart rate variability on 24-hour electrocardiogram recording were
      assessed in 40 patients with normal echocardiography and without evidence of
      coronary artery disease before and after 2 months of oral treatment with
      flecainide (321 +/- 57 mg/day) prescribed for Wolff Parkinson White syndrome with
      circus movement tachycardia. Flecainide significantly decreased all parameters of
      heart rate variability in the time domain (median delta% -10% to -25%) and in the
      frequency domain (median delta% -27% to -38%), including the markers of vagal
      activity. There was no correlation between plasma concentrations of flecainide
      and reduction in heart rate variability. It was concluded that in subjects
      without coronary artery disease or congestive heart failure, flecainide decreases
      all the measurements of heart rate variability and this decrease is not related
      to plasma concentrations of flecainide.

PMID- 9926281
TI  - The limits of evidence-based cardiovascular therapy.

PMID- 9926282
TI  - Ischemic preconditioning of the isolated perfused working guinea pig heart.

PMID- 9926283
TI  - Reduction of infarct size in isolated rat heart by CsA and FK506: possible role
      of phosphatase inhibition.

PMID- 9926284
TI  - Tissue kallikreins structure, regulation, and participation in mammalian
      physiology and disease.

PMID- 9926285
TI  - The kinin system in rhinitis and asthma.
AB  - The past decade has seen renewed interest in the potential role of kinins in
      airway diseases. The correlation between kinin generation and symptoms of
      inflammation, together with the demonstration that administration of kinins to
      the airway mucosa can induce relevant symptoms, provides strong circumstantial
      support for a role of kinins in the pathogenesis of airway diseases, such as
      allergic and viral rhinitis and asthma. Definitive studies of the effects of
      blockade of kinin actions on symptomatic responses, however, are still needed.
      The effects of kinins in the airways, and the mechanisms by which they exert
      their actions clearly vary depending on the presence of inflammation in the
      airways. Although a growing body of evidence implicates activation of sensory
      nerves as an important component of kinin effects in inflamed airways, the
      components of inflammation that modify the response of these sensory nerves, the
      mechanisms by which neuronal responsiveness alters, and the degree of selectivity
      of neuronal activation to bradykinin are all topics that require further
      delineation.

PMID- 9926286
TI  - The plasma kallikrein-kinin system in sepsis, inflammatory arthritis, and
      enterocolitis.

PMID- 9926287
TI  - Kinin receptors.
AB  - Rapid developments are expected in the molecular pharmacology of both B1, and B2
      types of kinin receptors, since the underlying genetic structures are now known
      and widely studied. The consequences of kinin receptor duality and
      physiopathological regulation have not yet been fully appreciated. Medicinal
      chemistry is also an active front of research in kinin pharmacology, as more
      effective drugs targeted at kinin receptors are regularly reported. Various
      complementary molecular approaches (the receptor binding, cloning,
      immunoreacting, mutagenesis, inactivation, the study of regulation, allelic
      polymorphisms, and so forth) are expanding our knowledge of the role of kinins in
      allergy, inflammation, and singularly, renal medicine.

PMID- 9926289
TI  - Female sex hormones and colorectal cancer.

PMID- 9926290
TI  - Colorectal cancer and hormone replacement therapy: an unexpected finding.
AB  - Over the last two decades, mortality rates for colorectal cancer in many
      developed countries have declined in women but not in men. A role of exogenous
      female hormones (i.e. oral contraceptives and hormone replacement therapy (HRT)
      in such different trends is possible. Seven cohort studies reported information
      on HRT use and colorectal cancer risk, for a total of over 2,400 cases. Most
      studies showed relative risks (RRs) around or below unity. A significant inverse
      association was found in two cohort investigations, including the largest one
      dealing with fatal colon cancer. Of 12 case-control studies, for a total of over
      5,000 cases, five reported 20-40% significant risk reductions among ever-users of
      HRT. Two additional investigations showed moderate, non-significant inverse
      associations. Studies showing an inverse association between HRT use and
      colorectal cancer were among the largest and best controlled ones. The apparent
      protection tended to be stronger among recent users. Differences in RRs by
      duration of HRT use and anatomic subsite were not consistent, but the protective
      effect seemed stronger in most recent publications. Available studies support the
      possibility of an inverse association between colorectal cancer and HRT, but
      prevention and surveillance bias cannot be ruled out.

PMID- 9926291
TI  - Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori
      infection in gastritis and gastric precancerous lesions in humans.
AB  - Chronic inflammation induced by Helicobacter pylori infection has been associated
      with an increased risk of stomach cancer. We have analysed 167 stomach biopsies
      from 99 patients for H. pylori infection and immunohistochemically for the
      expression of inducible nitric oxide synthase (iNOS), catalase and superoxide
      dismutases (SODs) as markers of oxidative stress. Biopsies were graded as follows
      on the basis of histology: normal, superficial gastritis, variable severity of
      atrophic gastritis with or without intestinal metaplasia, and dysplasia. iNOS was
      detected in inflammatory cells in all types of gastritis with or without H.
      pylori infection and independently of its severity. In foveolar cells, iNOS was
      observed in approximately 25% of all biopsies showing any type of gastritis, but
      in a markedly higher proportion of dysplastic samples. Catalase and Mn-type SOD
      in inflammatory cells and catalase in foveolar cells were more frequently
      observed in marked atrophic gastritis biopsies than in less severe gastritis.
      Individual differences were found in the expression of these enzymes within
      groups with the same severity of gastritis. Prolonged oxidative stress in severe
      gastritis and dysplasia may play an important role in gastric carcinogenesis,
      through increased damage of DNA and tissue by reactive oxygen and nitrogen
      species.

PMID- 9926292
TI  - Effects of high dose vitamin C treatment on Helicobacter pylori infection and
      total vitamin C concentration in gastric juice.
AB  - Low gastric juice total vitamin C concentration in the presence of Helicobacter
      pylori (H. pylori) infection probably plays a role in gastric carcinogenesis. In
      vitro vitamin C has been shown to inhibit the growth of H. pylori. The aims of
      this study were to determine the effect of high dose vitamin C administration on
      H. pylori infection and on gastric juice total vitamin C concentration in
      patients with H. pylori related chronic gastritis. Sixty patients with dyspeptic
      symptoms and proven chronic gastritis and H. pylori infection, who were
      undergoing routine endoscopy, entered the study after giving informed consent.
      They were randomly coded into two treatment groups. Group 1 (controls, n = 28)
      were treated with antacids for 4 weeks and Group 2 (n = 32) received vitamin C 5g
      daily also for 4 weeks. Nine patients did not complete the study and were
      excluded. Plasma and gastric juice total vitamin C levels were measured at
      baseline, at the end of 4 weeks treatment and again 4 weeks after treatment
      cessation. In the control group H. pylori infection remained unchanged in all 24
      patients throughout as did the mean gastric juice total vitamin C concentration.
      However, in the vitamin C treated group eight of 27 patients (30%) who completed
      the treatment course the H. pylori infection was eradicated (P = 0.01). In these
      patients the mean gastric juice total vitamin C concentration rose significantly
      from 7.2 +/- 1.6 micrograms/ml after 4 weeks treatment (P < M 0.001) and 19.8
      micrograms/ml 4 weeks after treatment was discontinued (P < 0.001). In the
      remaining 19 patients with persistent H. pylori infection, the mean gastric juice
      total vitamin C concentration rose less than in those with successful H. pylori
      eradication; 6.3 +/- 1.7 micrograms/ml before treatment, 10.8 +/- 1.5
      micrograms/ml after 4 weeks treatment (P < 0.05) and a return to pre-treatment
      levels (7.1 +/- 2.7 micrograms/ml) 4 weeks after vitamin C intake stopped. There
      were no side effects of vitamin C treatment. This study has shown that 4 weeks
      daily high dose vitamin C treatment in H. pylori infected patients with chronic
      gastritis resulted in apparent H. pylori eradication in 30% of those treated. In
      those patients there was also a highly significant rise in gastric juice total
      vitamin C concentration which persisted for at least 4 weeks after the treatment
      ceased. A significant, though less marked, gastric juice total vitamin C
      concentration increase was observed during vitamin C treatment even in subjects
      with persistent H. pylori infection, though this was not maintained after
      treatment ended. The mechanism whereby vitamin C treatment appeared to result in
      H. pylori eradication is unclear. Further confirmatory studies are indicated.

PMID- 9926288
TI  - Bradykinin formation. Plasma and tissue pathways and cellular interactions.

PMID- 9926293
TI  - Diet, alcohol, coffee and pancreatic cancer: final results from an Italian study.
AB  - The relation between selected indicator foods, alcohol and coffee intake, and the
      risk of pancreatic cancer was evaluated in a case-control study conducted between
      1983 and 1992 in northern Italy on 362 patients with histologically confirmed,
      incident cancers of the pancreas, and 1,552 controls in hospital for acute, non
      neoplastic diseases. Odds ratios (ORs) for subsequent tertiles of intake were
      computed after allowance for sociodemographic factors and tobacco smoking.
      Pancreatic cancer risk was directly associated with consumption of meat (OR for
      the highest frequency tertile = 1.43), liver (OR = 1.43) and ham and sausages (OR
      = 1.64), and inversely with consumption of fresh fruit (OR = 0.59), fish (OR =
      0.65) and olive oil (OR = 0.58). No appreciable association was found with coffee
      (OR = 1.21) and alcohol consumption (OR = 1.20). A summary score was derived by
      summing the six related food items; compared to the lowest level, the OR was 2.7
      for the highest quintile, and the population attributable risk was 36% (95%
      confidence interval, 15-57%), indicating the scope of diet for the prevention of
      this common neoplasm in the Italian population.

PMID- 9926294
TI  - Monounsaturated and other types of fat, and the risk of breast cancer.
AB  - We considered the role of monounsaturated and other types of fats on breast
      carcinogenesis, using data from a case-control study of 2,569 incident,
      histologically confirmed cases of breast cancer and 2,588 controls from six
      Italian areas. The multivariate odds ratios, adjusted for age, education, parity,
      menopausal status plus various sources of energy and types of fats, were 1.10
      (95% confidence interval 0.99-1.23) for an increase of 10 g/day of saturated fat
      intake, 0.99 (0.94-1.04) for an increase of 10 g/day of monounsaturated fats, and
      0.91 (0.87-0.96) for an increase of 5 g/day of polyunsaturated fats. The present
      data confirm that saturated, but not mono- or polyunsaturated fats, are directly,
      though moderately, related to breast cancer risk.

PMID- 9926295
TI  - Induction of quinone reductase by a methanol extract of Scutellaria baicalensis
      and its flavonoids in murine Hepa 1c1c7 cells.
AB  - The effect of extracts of scutellariae radix (Scutellaria baicalensis Georgi) and
      its flavonoids, baicalin, baicalein and wogonin, on induction of quinone
      reductase (QR) in the Hepa 1c1c7 murine hepatoma cell line was examined. A
      significant and dose-dependent induction of QR activity was observed in the
      methanol extract of scutellariae radix and baicalin. HPCL analysis showed that
      baicalin was contained as a main component in the methanol extract of
      scutellariae radix, indicating that baicalin may be the major active principle of
      QR induction mediated by scutellariae radix extract. To elucidate the mechanism
      of baicalin-mediated induction of QR enzyme activity, the effect on QR mRNA
      levels in Hepa 1c1c7 cell cultures was investigated. Using reverse transcriptase
      polymerase chain reaction techniques, time- and dose-dependent induction of QR
      mRNA levels by baicalin were demonstrated in Hepa 1c1c7 cells. On the basis of
      these results, the scutellariae radix extract or baicalin can be regarded as a
      readily available, promising, novel cancer chemopreventive agent.

PMID- 9926296
TI  - European country comparisons provide evidence of a link between colon cancer and
      adenocarcinoma development in the lung but not the oesophagus.
AB  - Relative incidence rates of lung cancers demonstrate marked international
      variation in values for the different histological sub-types. In order to
      determine whether adenocarcinomas (ACs) in this site might share risk factors
      with other ACs, for example, in the breast, prostate, oesophagus and colon, a
      comparison of data in the IARC/WHO Cancer Incidence in Five Continents (Volume
      VII) was made for selected registries in Europe. Significant correlations were
      found between lung AC incidences/100,000 population and prostate and colon
      cancers in males (P < 0.005 and P < 0.05, respectively) and for breast and colon
      in females (P < 0.05 for both). Partial correlation coefficients were significant
      for lung and colon (P < 0.001) and prostate and colon (P < 0.005) in men, and for
      breast and colon in women (P < 0.005). A significant negative correlation with
      prostate cancer was noted for lung ACs in men. The results provide support for
      shared risk factors between lung Acs and colon cancers but do not indicate any
      link with AC development in the oesophagus. Data from registries in the UK and
      Italy were remarkable for high incidences of oesophageal and lung ACs,
      respectively, pointing to major differences in environmental risk factor or
      beneficial influence acting on these sites between the two countries.

PMID- 9926297
TI  - Blood transfusion requirements in children with blunt spleen and liver injuries.
AB  - The records of 174 children sustaining blunt spleen and liver injuries in a 16
      year period were analyzed retrospectively to determine blood transfusion
      requirements in surgically versus conservatively managed patients. The whole
      study group consisted of 97 spleen, 70 liver, and 7 combined spleen and liver
      injuries respectively. Seventy-eight patients were managed conservatively while
      96 children had undergone various operative procedures. The hematocrit (Hct)
      values, transfused blood volumes (ml/kg), and length of hospital stay were
      compared between the non-operative and operative treatment groups. Although the
      initial Hct values were found to be similar in non-operative versus operative
      groups (26.7% +/- 2.7% vs. 24.8% +/- 3.5%), transfused blood volumes were
      significantly higher in the surgically treated group respectively (20.9 ml/kg vs.
      39.5 ml/kg) (p < 0.05). Similarly, mean length of hospital stay was longer in the
      surgical groups. Associated injuries were seen in 105 (60.3%) patients
      distributed randomly among two study groups. Twelve patients in the series died
      of other system/organ involvement. There were no deaths in isolated spleen and/or
      liver injuries. Increased blood transfusion requirement in surgical groups may be
      due to excessive bleeding prior to the operation which virtually provides the
      indication for laparotomy. Manipulation and suturing enhances additional bleeding
      to elevate the total volume to be delivered. Operative choice should be spared
      for very selected cases, and conservative management is safe; procedures such as
      splenorrhaphy are not superior to observation therapy as a means of controlling
      intraabdominal bleeding.

PMID- 9926298
TI  - Amnio-allantoic fluid exchange for the prevention of intestinal damage in
      gastroschisis. III: Determination of the waste products removed by exchange.
AB  - Experimental amnio-allantoic fluid (AAF) exchange has been shown to prevent
      intestinal damage in the chicken embryo gastroschisis model. AAF contains both
      urinary and gastrointestinal waste products (UWP and GIWP). An experimental study
      was performed to find the waste products responsible for this intestinal damage.
      Gastroschisis was created in 20 chick embryos. Half were treated with AAF
      exchange, the other half were not treated. AAF samples were obtained for
      biochemical determination of urea nitrogen and creatinine as UWP, bile acids and
      bilirubin as GIWP at the end of the incubation. Intestines were evaluated by
      light microscopy. While GIWP (Bile salts and bilirubin) were significantly
      removed from AAF by exchange, the levels of UWP (urea nitrogen and creatinine)
      were unaffected. Intestinal wall thickness was less in the exchange group
      compared to the untreated group. The unchanged levels of UWP after AAF exchange
      may be attributed to their relatively rapid production compared to GIWP. Dilution
      of GIWPs by AAF exchange results in prevention of the intestinal damage in
      gastroschisis.

PMID- 9926299
TI  - Recurrent congenital diaphragmatic hernia; which factors are involved?
AB  - The medical records of 66 surviving children born with congenital posterolateral
      diaphragmatic hernia (CDH) were reviewed to determine which factors are involved
      in the development of a recurrent hernia. Fifty-seven patients had a left-sided
      defect and 9 patients had a right sided defect. In 54 patients the defect was
      closed primarily and 12 patients required a prosthetic patch. Nine of the 66
      patients (14%)--5 patients (9%) with a left-sided defect and 4 patients (44%)
      with a right-sided defect--developed a recurrent hernia on the average of 4.0
      months (range 0.2-6.9) after the initial repair. Except for one, all patients
      with a recurrence presented with dyspnoea (n = 5) and/or feeding problems (n =
      6). Of these 9 recurrences 4 patients (7%) had primary closure of the defect and
      in 5 patients (42%) a prosthetic patch was required. Four of the 11 patients
      (36%) who needed extracorporeal membrane oxygenation (ECMO) had a recurrence
      versus 5 patients (9%) who were conventionally treated. A hernial sac was found
      in 4 patients during the repair of the recurrent hernia. In 3 of them the initial
      defect was closed primarily. In conclusion, large-patch repaired defects and
      right-sided defects are risk factors for the development of a recurrent hernia.
      Furthermore the lack of a biological union between the sutured patch and the
      diaphragm tissue remnants is likely to be the cause of a reherniation. Meticulous
      inspection for a hernial sac during the initial operation could reduce the
      incidence of a reherniation.

PMID- 9926300
TI  - The role of partial splenectomy in children with thalassemia.
AB  - Partial splenectomy was performed on 12 patients with thalassemia (9 beta
      thalassemia major and 3 Hb H disease) to reduce blood transfusion requirements.
      The indication for partial splenectomy was the presence of splenomegaly and
      increased blood transfusion requirements (i.e. Hb drop > 0.5 g per week). Their
      ages ranged from 3 to 10 years (mean 6.9 years). On follow-up, ranging from 1.1
      5.5 years (mean 2.6 years), two of the three patients with Hb H disease required
      no more blood transfusions while the third continued to receive blood
      transfusions, but at a lower frequency. For those with beta-thalassemia major,
      the transfusion requirements and Hb drop per week decreased in the majority of
      patients. This is specially so during the first 1-2 years following partial
      splenectomy. In all, about 1/3 of the size of the normal spleen was preserved
      (either upper or lower pole) which was judged functional as there has been no
      significant infection in any of the patients, no change in IgM level, no Howell
      Jolly bodies and visualization on scintigraphy. Partial splenectomy is
      recommended to start with for those with Hb H disease. For patients with beta
      thalassemia major, partial splenectomy is beneficial as a temporary measure and
      in those children who are less than 5 years of age, as they are at greater risk
      of post splenectomy sepsis.

PMID- 9926301
TI  - Interest of direct radionuclide cystography in repeated urinary tract infection
      exploration in childhood.
AB  - 108 children with repeated urinary tract infection were examined both with direct
      contrast cystography and radionuclide cystography. There was a good correlation
      between the two procedures in the majority of the cases (79), but in 21 cases,
      direct radionuclide cystography alone was positive and for 8 other children,
      direct contrast cystography showed a low-grade vesico-ureteric reflux even though
      radionuclide cystography was negative. When comparing the two procedures and
      taking into consideration the age of the patients we find that radionuclide
      cystography is more sensitive to detect vesico-ureteric reflux in the younger
      population (p < 0.02). This advantage is less clear for older children who more
      often present a low-grade reflux. Low radiation exposure is also a great
      advantage of radionuclide cystography, but anatomic definition is better with
      contrast cystography. It seems thus that the two procedures complement rather
      than rival each other. Their respective interest for evaluation of repeated
      urinary tract infection in children therefore depends on age, attain-ability of
      the procedure, and the possibility of a bladder or ureteral abnormality. Quite a
      few authors consider radionuclide cystography as at least as valid as contrast
      cystography, and even more sensitive. We have attempted to compare both
      procedures and to determine their respective role in repeated urinary tract
      infection exploration.

PMID- 9926302
TI  - Treatment of small-bowel obstruction by laparoscopy in children multicentric
      study. GECI. Groupe d'Etude en Coeliochirurgie Infantile.
AB  - In May 1996, the team working on infantile laparoscopy (GECI) carried out a
      retrospective study (using questionnaires) to analyse the use of laparoscopy in
      child postoperative obstructions (involving bands or adhesions). Of the 86
      laparoscopic attempts, 66 could have been performed without conversion. Technical
      difficulties were responsible for the majority of the conversions performed on
      children aged 3 years younger than the average age in this study (10 years old).
      Digestive perforation accounts for a fifth of conversions, the perforations
      either occurring when the operational trocars were introduced (3 cases), or
      during viscerolysis (2 cases). For 5 children the treatment failed at an early
      stage (in the month following the operation). Relapses occurred in 3 children,
      usually at a later date (between 6 months and 3 years). Laparoscopic treatment of
      bowel obstruction should always be attempted, for as the results of the study
      show, morbidity is low and mortality is nil and the postoperative phase is quick
      and painless.

PMID- 9926303
TI  - Conservative treatment in primary neonatal megaureter.
AB  - The authors report their experience on 22 neonates (14 males and 8 females) with
      primary megaureter. In 18 patients a prenatal diagnosis was available, in the
      other four the diagnosis was suspected during a neonatal ultrasound screening.
      The dilatation involved the right ureter 7 times and the left 13 times, in 2
      patients it was bilateral. Intravenous urography documented a type I ureteral
      dilatation in 2 renal units (8.3%), a type II in 9 (37.5%) and a type III
      dilatation in 13 (54.2%). Radionuclide scan (Tc99m DTPA) demonstrated in all the
      renal units with megaureter a stable function. From diuretic renal scan, non
      obstruction appeared in 19 (83%), obstruction in 2 (8.5%) and an equivocal result
      in the remaining 2. Antibiotic prophylaxis was administered to all patients.
      Follow-up period ranged from 18 to 54 months. The 2 obstructed megaureter were
      surgically treated. Other 2 patients with type III dilatation and non-obstructing
      megaureter underwent surgery at 18 and 24 months of age respectively. The
      remaining 17 patients were all conservatively treated. The 2 patients with type I
      dilatation resolved spontaneously. Of 9 patients with type II megaureter the
      dilatation resolved in 6 patients and 3 patients had a good reduction. In the
      remaining 8 patients with type III megaureter, the dilatation resolved in 5 cases
      and 3 patients had only a fair reduction. The renal function (> 40%) remained
      stable in all the patients.

PMID- 9926304
TI  - The place of Mitrofanoff neourethra in the repair of exstrophy-epispadias
      complex.
AB  - The authors present their experience with seven patients having an exstrophy
      epispadias complex who had undergone Young-Dees-Leadbetter bladder neck
      reconstruction with an adjuvant Mitrofanoff neourethra. All the patients, but
      one, were male with a mean age of 7.4 +/- 3.9 years. Six of them had had previous
      primary closure of their exstrophied bladders accompanied by anterior diagonal
      iliac osteostomies, and one having pure epispadias had an incompetent bladder
      neck and a very low bladder capacity. Four of these patients had breakdown of
      their reconstructed bladder necks due to clean intermittent catheterization (CIC)
      via urethra. Ileocystoplasties were performed in all of the patients for their
      unacceptably low bladder capacities (mean 20.9 +/- 12.9 ml) with an adjuvant
      Mitrofanoff neourethra. The patients were put on CIC every 3-4 hours via
      Mitrofanoff channel. Six were totally continent, and one had to use a pad during
      daytime. There were no complications related to the Mitrofanoff stoma except two
      patients complained about temporary difficulty on catheterization. The authors
      conclude that incorporating a Mitrofanoff stoma to bladder neck reconstruction
      procedures in exstrophy-epispadias complex, prevents injury to the bladder neck
      during CIC, and thus lowers the risk and incidence of failure.

PMID- 9926305
TI  - Utility of helical CT for diagnosis and operative planning in tracheomalacia
      after repair of esophageal atresia.
AB  - We utilized helical computed tomography (CT) in three infants (aged 1 to 5
      months) with tracheomalacia after repair of esophageal atresia. Helical CT was
      used for preoperative diagnosis and operative planning. At the time of
      aortosternopexy, it is often difficult to determine the direction of suture
      traction to yield the largest tracheal lumen. The helical CT was useful not only
      for diagnosis of tracheomalacia but also for operative planning of
      aortosternopexy.

PMID- 9926306
TI  - Esophageal leiomyomatosis in children: report of a case and review of the
      literature.
AB  - The authors describe a case of a 5-years-old girl affected by diffuse oesophageal
      leiomyomatosis presenting with progressive dysphagia, cyanosis, recurrent
      pneumonia and retrosternal pain. She also suffered from occasional constipation
      due to perineal involvement by the disease and had a past history of recurrent
      microscopic hematuria, suggesting an association with an Alport-like syndrome.
      Only 24 cases of esophageal leiomyomatosis could be found in the medical
      literature in children aged less than 14 years, confirming the rarity of the
      disease. A clinical analysis of all cases reviewed from the literature is made,
      stressing the importance of an accurate preoperative diagnosis for the choice of
      proper surgical treatment to avoid recurrence.

PMID- 9926308
TI  - Minimally conjoined omphalopagus twinning: a case report.
AB  - In most omphalopagus twinnings, joined structures include the gastrointestinal
      tract, liver, biliary tree and bladder. In some instances of omphalopagus, joined
      attachments are limited to the intestine and bladder. Eight cases like these,
      that are also called minimally conjoined twinning, have been reported before.
      This article describes a set of twins who were joined by an omphalocele sac and
      small bowel. There were several loops of bowel in the conjoined omphalocele sac
      without any evidence of liver. One of the twins had atresia of the colon, rectum
      and anus and the other had a cloacal anomaly. The twins were separated at the
      18th hour after birth due to intestinal obstruction. One of the twins survived,
      but the other died on the second day postoperatively.

PMID- 9926307
TI  - Bilateral and multilobar cystic adenomatoid malformation of the lung.
AB  - We report a case of bilateral and multilobar congenital cystic adenomatoid
      malformation (CCAM) in a four-months-old child with good clinical results after
      resections of the lesions. This is a relatively rare form of pulmonary disease.
      The final prognosis in these patients depends on the type of malformation, the
      presence or absence of fetal hydrops and on the extent of affected lung. Few
      cases of multiple involvement have been reported. We will consider the
      physiopathological aspects of the case, late clinical presentation and treatment
      and the positive surgical response based on the findings of the functional and
      anatomic imaging studies.

PMID- 9926309
TI  - Budd-Chiari syndrome following repair of a giant omphalocele.
AB  - We report a case of Budd-Chiari syndrome following repair of a giant omphalocele.
      Thrombosis of hepatic veins and of retrohepatic inferior vena cava may result
      from direct pressure on the hepatic venous outlet after visceral reduction and
      final abdominal wall closure.

PMID- 9926310
TI  - Heterotopic pancreatic tissue at umbilicus.
AB  - Heterotopic pancreatic tissue at the umbilicus is a very rare anomaly with only 4
      cases previously reported in the literature: we describe our experience with 2
      additional cases.

PMID- 9926311
TI  - Torsion of vermiform appendix: value of ultrasonographic findings.
AB  - A case of torsion of the vermiform appendix is described in a five-year-old boy
      with a two-day history of right-sided abdominal pain. No associated abdominal
      tenderness was reported, no vomiting nor fever. The pain was localized in the
      same place for 24 hours and became more severe and constant. Blood film showed a
      normal white cell count. After two ultrasonographic examinations in the course of
      24 hours, the sign of a distended intestinal loop became constant. With the
      diagnosis of mucous-producing appendicular lesions or appendicular torsion, a
      laparotomy was performed. The appendix was severely congested and gangrenous;
      there was a 360-degree anticlockwise twist in its base. The related literature is
      reviewed and the value of the ultrasound scanner images and the possible
      mechanism involved is discussed.

PMID- 9926312
TI  - Colonic atresia associated with Hirschsprung's disease: it is not a diagnostic
      challenge.
AB  - Colonic atresia Hirschsprung's disease association (CAHDA) is usually diagnosed
      after several failures of intestinal anastomoses. Having previously reported one
      of the cases of CAHDA, we established the diagnosis in a patient before
      attempting intestinal anastomosis for stoma closure. We herein report the first
      patient with CAHDA in the literature diagnosed before a therapeutic challenge. We
      recommend a biopsy of the distal colonic segment either during initial laparotomy
      or before attempting intestinal anastomosis for closure of colostomy to prevent
      therapeutic challenge in the patients with colonic atresia.

PMID- 9926313
TI  - Congenital prepubic sinus: possible variant of dorsal urethral duplication.
AB  - Congenital prepubic sinus is a rare anomaly of the urinary tract. There have been
      few cases in the literature since the first report by Campbell et al in 1987. We
      present three male cases with this anomaly.

PMID- 9926314
TI  - Tumoral calcinosis and atypical juvenile dermatomyositis: case report.
AB  - Tumoral calcinosis is a rare, benign calcification of soft tissues in
      periarticular areas. It can manifest as an isolated disease or as part of an
      underlying disorder. We report a case of a 6-year-old girl who presented with
      tumoral calcinosis of her left knee in association with atypical juvenile
      dermatomyositis. Finally, we discuss operative and non-operative treatment
      strategies of tumoral calcinosis in children and adults.

PMID- 9926315
TI  - Mother and teacher reports of behaviour and perceived self-competence of children
      with hydrocephalus.
AB  - The present study was designed to explore the social and behavioural functioning
      of children with hydrocephalus. The sample comprised 14 children with
      hydrocephalus (without spina bifida) and 14 controls with no history of
      neurological impairment matched for age and gender. Children were asked to report
      on their self-perceptions of academic and physical competence and on peer and
      maternal acceptance. In addition, mothers and teachers provided reports of the
      behavioural adjustment of both groups and mothers completed a questionnaire
      measuring locus of control orientation. Mothers of children with hydrocephalus
      also responded to a series of open-ended questions, their thoughts and feelings
      about the experience of having a child with hydrocephalus. Analyses of the data
      revealed that there was no difference in the self-perceptions of the two groups
      of children, although there was a trend for children with hydrocephalus to rate
      themselves as being lower in physical competence. There was a clear association
      between the presence of hydrocephalus and behaviour problems, with evidence of
      internalising and externalising problems being evident in the reports of both
      mothers and teachers, although the extent of agreement between the two informants
      was low. Maternal locus of control was related to behaviour problems in children
      with hydrocephalus, with a more external orientation being related to more
      behaviour problems. It is suggested that future researchers need to 1) focus on
      children's behaviour in context, 2) solicit data from a range of informants and
      3) consider the complex transactions between biological and psychological factors
      to gain a fuller understanding of how hydrocephalus shapes children's
      development.

PMID- 9926317
TI  - Pre-natal brain development of fetuses with a myelomeningocele.
AB  - Biometric measurements of 21 fetuses referred to the Fetal Management Unit at St.
      Mary's in Manchester with a diagnosis of myelomeningocele were analysed. Five
      fetuses had more than 3 sets of measurements carried out, the last of which were
      performed during the 3rd trimester. The majority of the head circumference
      measurements were on or below the 3rd percentile for normal head size whilst
      almost all of the cerebral ventricular atrial measurements were more than 10 mm,
      a figure generally accepted as being at the upper limit of normal, measurements
      above this indicate that ventriculomegaly is present. In normal fetuses the
      atrial measurement is constant at or below 10 mm throughout gestation, but in the
      fetuses with a myelomeningocele the atrial measurements got progressively larger
      as gestation proceeded. Because their head circumferences did not increase
      disproportionately quickly, there was no evidence that the fetuses were
      developing hydrocephalus in utero, rather the large atrial measurements were
      indicative of poor development of the cerebral hemispheres. These findings
      together with the Arnold-Chiari malformation and the abnormalities in the spinal
      cord indicate that the central nervous system in its entirety is abnormally
      developed in fetuses with a myelomeningocele.

PMID- 9926316
TI  - The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked
      hydrocephalus.
AB  - Neural cell adhesion molecules (CAM) play important roles in neural development,
      neurite outgrowth, axonal guidance, fasciculation and synapse formation.
      Neuropathological studies of X-linked hydrocephalus (XLH) associated with L1 CAM
      mutations emphasize marked hypoplasia of the pyramidal tract, agenesis of the
      corpus callosum and septum pellucidum, and a thin cerebral mantle with
      hypoplastic white matter, but there are no detailed studies of the cerebral
      cortex in the literature. We report clinical, neuroimaging, and neuropathological
      findings in three boys with XLH. All had severe congenital hydrocephalus with
      marked thinning of the cerebral mantle and severe development disabilities. The
      brain specimens from the three boys showed both pachygyria and polymicrogyria,
      hypoplasia of the medullary pyramids, hypoplasia of the corpus callosum, small
      anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but
      patent aqueduct was present in all three brains. Despite the extensive cerebral
      malformations, the cortex in all three brains showed normal-appearing laminar
      cortical neuronal architecture and absence of gliosis. In XLH, it is likely that
      the poor developmental outcome of spasticity, contractures and severe mental
      retardation results from a disturbance of neuronal connectivity, fasciculation,
      and synapse formation rather than aqueductal stenosis, increased intracranial
      pressure, or abnormal neuroblast migration.

PMID- 9926318
TI  - Anatomy of the spinal cord in patients with meningomyelocele with and without
      hypoplasia or hydromyelia.
AB  - We compared the cross-sectional areas of spinal cords of patients with normal
      cords to the area of patients with meningomyelocele. The control group consisted
      of examinations of 27 patients with normal spinal cords providing 1547 axial
      images at 20 levels, C2-L2. The meningomyelocele group consisted of 67 MRI
      examinations of 41 patients, providing 4,095 axial images at 23 levels C2 to S1.
      Thirty-four examinations were of 21 patients with minimal hydromyelia, 7
      examinations were of 3 patients with operable hydromyelia, and 26 examinations
      were of 17 patients without hydromyelia. In an additional analysis, we selected
      those meningomyelocele patients with cord tethering but without hydromyelia or
      hypoplasia (53 examinations of 30 patients) and compared them to symptomatic
      hypoplasia cases (9 examinations of 6 patients). The symptomatic hypoplasia cases
      were chosen because of progressive loss of muscle strength and worsening
      spasticity not relieved by surgical adhesiolysis. The test, retest error was 5.6%
      with differences between the means of repeated readings not being significant.
      All tests for significance were paired T test. The areas of spine levels C7-L2
      for the controls were significantly larger than for the meningomyelocele patients
      (p = 0.000007). Including all levels C2-S1, the minimal hydromyelia cases were
      not significantly different from those without hydromyelia (p = 0.5). The areas
      C2-S1 of operable hydromyelia cases were larger than both non-shunted minimal
      hydromyelia (p = 0.00009) and of meningomyelocele patients without hydromyelia (p
      = 0.00003). The areas C7-L2, of hypoplasia cases were significantly smaller
      compared to the "normal" meningomyelocele cases (p = 0.0004). These data suggest
      that hydromyelia stimulates overgrowth of the cord, as does hydrocephalus of the
      brain, and that adhesiolysis procedures are of no value with hypoplasia of the
      spinal cord.

PMID- 9926319
TI  - Surgical treatment of scoliosis associated with myelomeningocele.
AB  - Twenty-nine patients (mean age 12 years) with severe thoracolumbar and lumbar
      scoliosis due to myelomeningocele were treated by spinal fusion (7 by posterior
      arthrodesis with instrumentation, 3 by anterior arthrodesis with instrumentation,
      19 by combined anterior and posterior fusion with instrumentation). Fusion was
      extended to the sacrum in 15 patients. Mean period of follow-up was 6.2 years.
      The average Cobb angle changes were as follows: thoracic and thoracolumbar curves
      preoperatively 86 degrees to 45 degrees at follow-up (the final average curve
      correction was 47%); lumbar curves preoperatively 97 degrees to 48 degrees at
      follow-up (the final average curve correction was 50%). Average pelvis obliquity
      changed from 26 degrees to 13 degrees at follow-up with an average correction of
      49%. The combined anterior and posterior instrumentation and fusion gave the best
      correction of deformity (the final average thoracic and thoracolumbar curve
      correction was 55%; the final average lumbar curve correction was 61%).
      Independent of the method of stabilization, post-operative wound infection was a
      serious problem (24%). The combined fusion-instrumentation method reduced the
      rate of pseudoarthrosis to 14%.

PMID- 9926320
TI  - Pitfalls in shunting of hydrocephalus--clinical reality and improvement by the
      hydrostatic dual-switch valve.
AB  - The hydrostatic dual-switch valve (DSV) was implanted in 56 patients suffering
      from hydrocephalus of different causes. Evaluation of the clinical status 3 and 6
      months after the operation revealed excellent and good neurological recoveries in
      the vast majority of cases. Only 7 patients demonstrated an unsatisfactory result
      according to the grading of Stein and Langfitt. The CT follow-up, evaluated by
      the reduction of the Evans index, was characterized by only minimal or even no
      reduction of the ventricular size in more than half of the patients. Only 2
      patients of our series developed overdrainage-related problems. 5 cases are
      presented to illucidate the danger of overdrainage resulting from the
      implantation of conventional differential-pressure valves, and the possible
      solution of this problem by hydrostatic devices like the DSV. Our series gives
      strong evidence, that reestablishing physiological pressure-ranges after shunting
      is paralleled by a good clinical outcome independent of the ventricular size
      after shunting.

PMID- 9926321
TI  - Pre-natal diagnosis of occult spinal dysraphism by ultrasonography and post-natal
      evaluation by MR scanning.
AB  - Eight children born with occult spinal dysraphism were diagnosed in utero by
      ultrasonography. Post-natally, they were evaluated by MR scans. The ultrasound
      scans in all 8 fetuses revealed a spina bifida: the spinal cord was long in 5 and
      in 3 a meningocele was thought to be present, however, in 1, a post-natal MR scan
      revealed a lipomeningocele instead of a simple meningocele. In 3 fetuses an
      echogenic area was seen on the ultrasound scan which raised the possibility that
      an intradural lipoma was present, and was confirmed by post-natal MR scans. In 3
      fetuses vertebral body anomalies and an additional ossification centre in a
      midline bony spur together with widening of the spinal canal were seen in the
      lower lumbar region. The lesions in all 8 fetuses were skin-covered. None had
      ventriculomegaly or an Arnold-Chiari malformation. The prognosis for fetuses with
      spina bifida aperta is well documented in contrast to that for those with spina
      bifida occulta. The ability to identify a spinal dysraphic lesion pre-natally
      allows a more accurate assessment to be made of the likely outcome for an
      individual fetus.

PMID- 9926322
TI  - Nutritional survey of children and adolescents with myelomeningocele (MMC):
      overweight associated with reduced energy intake.
AB  - In patients affected by MMC both neurological and systemic dysfunctions may cause
      obesity and malnutrition. The aim of this study is a nutritional survey, with
      anthropometric assessment and dietary evaluation, of patients affected by MMC.
      CLINICAL MATERIALS AND METHODS: Anthropometric assessment, dietary evaluation,
      and a comprehensive assessment of motor impairment degree (MID) were performed in
      100 patients (54 males, 46 females) affected by MMC aged from 6 to 228 months
      (median 91 months). RESULTS: Fifty-five/100 children and adolescents with MMC
      were classified as normal or wellnourished and 5 at risk of malnutrition or
      malnourished, while another 40/100 patients were classified as marked overweight
      (weight-for-height or BMI above the 95th percentile). Deficit in height-for-age
      was observed in 34/100 patients; 12 of these patients presented with obesity.
      Dietary assessment evidenced that the majority of wellnourished patients (48/55)
      were consuming less than 80% or between 80% to 100% of recommended daily
      allowances (RDA) of energy. Overweight patients had an energy intake lower than
      their own RDA: 5 below 80%, 25 between 80% to 100%, and only 10 over 100% of RDA
      of energy for age and sex. No statistical correlation was found between
      nutritional status and MID, while there was a statistically significant
      difference between nutritional status and dietary intake (p = 0.005). DISCUSSION:
      Overweight is the most frequent nutritional disease in patients affected by MMC.
      Since in our experience on correlation with MID was found, we can speculate that
      childhood and adolescent obesity in patients with MMC occurs as a result of
      complex interactive factors, not strictly related to energy intake and MID.
      Nutritional surveillance and specific treatment programs for overweight MMC
      patients are essential to enhance their quality of life.

PMID- 9926323
TI  - Bowel dysfunction in spina bifida--an American experience with the ACE procedure.
AB  - Fecal incontinence remains a detriment to improved quality of life in many
      patients with spina bifida. Previous methods of conservative management
      frequently prove to be inadequate, causing many patients to withdraw from the
      social mainstream. Recent descriptions of procedures to provide access to the
      proximal colon for antegrade colonic enemas (ACE procedure) have provided a new
      approach to managing fecal incontinence. We report here our experience with these
      procedures in 43 patients with spina bifida. The background, techniques and
      outcomes of these procedures are discussed and a plea is made to consider this
      approach in all patients who are hampered in their social or vocational progress
      because of neurogenic anorectal dysfunction.

PMID- 9926324
TI  - Differential ventricular expansion in hydrocephalus.
AB  - In the large canine model of acquired obstructive hydrocephalus that we have
      developed recently, computer-assisted 3-dimensional morphometry has been
      performed on T1-weighted Spin Echo MRI images from adult dogs before and after
      the induction of hydrocephalus. To date, 7 hydrocephalic animals have been
      analyzed that survived 7-83 days (median = 54) after receiving injections of
      cyanoacrylate glue into the anterior fourth ventricle. Measurements were obtained
      from lateral, 3rd, and 4th ventricles. The volumes of the left and right lateral
      ventricles were symmetrical before and after induction. Mean lateral ventricle
      volume increased 424% from a baseline of 0.63 cc to a post-induction value of
      3.30 cc (p < 0.01 with unpaired t-test). In contrast, the 3rd ventricle expanded
      187% from a mean of 0.15 cc to 0.43 cc (p < 0.05). The combined volume of the
      lateral and 3rd ventricles increased 369% from a mean of 0.78 cc to 3.69 cc (p <
      0.01). Evans' ratios, which are used routinely in the clinical setting, were also
      obtained from linear measurements of the lateral ventricle width divided by brain
      width at the level of the foramen of Monro. These values exhibited only a 94%
      increase from mean baseline ratios of 0.17 to post-induction ratios of 0.33 (p <
      0.05). These findings indicate that in mechanically-induced obstructive
      hydrocephalus the relative expansion of the lateral ventricles is greater than
      that of the 3rd ventricle. In addition, volumetric measurements of the lateral
      and 3rd ventricles suggest that the extent of ventriculomegaly is 3-4 times
      greater than estimated by Evans' ratios.

PMID- 9926325
TI  - Cell death in the brain of the HTx rat.
AB  - The structural changes in the hydrocephalic brain suggest that cell death must be
      a significant factor in the loss of cortical mantle thickness and cell numbers.
      In the developing hydrocephalic brain a similar conclusion might also be reached.
      We present data suggesting that in the developing hydrocephalic HTx rat brain,
      there are at least two processes that underlie the structural deficit in the
      cortex. The first is abnormal development of the cortex probably resulting from a
      combination of the genetic defect and blockage of CSF circulation in the fetus.
      The second is a direct consequence of raised intracranial pressure and is
      manifested in a lack of development of glial cells in the neonatal brain and in
      the loss of myelination and neurones as pressure rises after birth, particularly
      after skull plate fusion. We find little evidence of increased cell death by
      apoptosis, recording instead a decrease in apoptotic index. There is evidence
      that necrosis must have occurred.

PMID- 9926326
TI  - Overnight shunt pressure monitoring in children.
AB  - We audited the value of overnight shunt pressure monitoring in 17 children with
      symptoms of possible shunt dysfunction but no other supportive evidence. The
      shunt was accessed by a 25G butterfly connected to a disposable arterial pressure
      monitor positioned on the ipsilateral shoulder whose output was recorded
      continuously, while noting posture, sleep state and symptoms. Initially traces
      were analysed only for the portion spent both asleep and supine or prone. Six
      showed pressure peaks while asleep: of these four underwent shunt revision with
      remission of their symptoms and two resolved spontaneously, one with a
      simultaneous resolution of a peritoneal CSF collection, but the other had a
      recurrence of symptoms after six months. Two more subsequently shown to have
      blocked shunts had normal traces while asleep but abnormal pressure peaks when
      awake and upright. Two showed pressure troughs: one responded to insertion of an
      antisyphon device and one resolved spontaneously. Five had normal traces while
      asleep and awake: symptoms resolved in three and persisted in two in whom later
      prolonged extradural monitoring with a fibre-optic transducer was also normal.
      Studies failed in two. We conclude that prolonged overnight shunt pressure
      monitoring with this technique is useful in diagnosing shunt dysfunction and that
      abnormalities detected while awake and upright are as significant as those
      detected asleep and supine or prone.

PMID- 9926327
TI  - A longitudinal study of cognitive abilities and achievement status of children
      with myelomeningocele and their relationship with clinical types.
AB  - Cognitive abilities and achievement status of 178 children with myelomeningocele
      (MMC) were examined with neuropsychological techniques. These children as a whole
      scored below the population average. Children with MMC and shunted hydrocephalus
      performed worse than the arrested (unshunted) and non-hydrocephalic children. The
      greater deficit occurred on the Performance IQ. 80.7% of the subjects attended
      normal school while, 19.3% received remedial instruction. The results of our
      study are consistent with a large body of literature indicating that children
      with shunted hydrocephalus demonstrate poorer development of non-verbal relative
      to verbal cognitive abilities.

PMID- 9926328
TI  - The relation between CSF pressure and ventricular dilatation in hydrocephalic HTx
      rats.
AB  - The relation between increased cerebrospinal fluid (CSF) pressure and ventricular
      enlargement in infantile hydrocephalus is uncertain, variable, and probably
      dependent on the etiology of the condition. The HTx rat has early-onset
      hydrocephalus due to aqueduct stenosis in late gestation with ventricular
      dilatation present in fetuses. Increased CSF pressure, however, is first detected
      at postnatal day 10 or later. How the transition from low pressure to raised
      pressure hydrocephalus takes place, is not clear. In order to study this, we
      investigated how CSF pressure is related to the magnitude of ventricular
      dilatation using hydrocephalic and control HTx rats at postnatal days 15 and 21.
      At 15 days, the CSF pressure for hydrocephalics was 31.1 +/- 3.6 mm H2O (mean +/-
      SEM) which was not significantly higher than the controls at 19.9 +/- 2.8 mm H2O.
      At 21 days, the pressure was significantly higher in hydrocephalics at 50.9 +/-
      7.5 mm H2O compared to 24.3 +/- 3.6 mm H2O for controls, p < 0.05. The mean
      volume of the lateral ventricles was 409.3 mm3 at day 15 and 478.8 mm3 at day 21,
      whereas age-matched control rats in a previous study had ventricles of 14 and 25
      mm3. At each age there was a significant linear relationship between CSF pressure
      and ventricle volume, p < 0.05 at day 15 and p < 0.01 at day 21. Closer
      examination of the data, however, showed that 5/10 hydrocephalics at day 15 and
      4/10 at day 21 had CSF pressures that were within the 95% confidence limits of
      the mean pressures for the control groups. The ventricle volumes of these low
      pressure hydrocephalics were between 100 and 280 mm3 which was several times
      larger than the ventricles in control rats. CSF pressure in the remaining 15 day
      rats ranged from 30 to 53 mm H2O and in the 21 day rats from 46 to 90 mm H2O and
      the ventricles were between 280 and 1050 mm3. The results suggest that up to a
      critical volume the infant rat brain can accommodate additional CSF without an
      increase in pressure. At this volume there is a "break point" beyond which
      additional fluid results in further expansion along with an increase in CSF
      pressure.

PMID- 9926329
TI  - Effects of prophylaxis on latex sensitization in children with spina bifida.

PMID- 9926330
TI  - Laparoscopy-assisted abdominal shunt revisions in children with hydrocephalus.
AB  - Abdominal shunt revisions are frequently necessary for ventriculoperitoneal shunt
      systems in children with hydrocephalus internus. There are many well-known
      problems related to abdominal shunt revisions such as difficulties in reaching
      the abdominal cavity, intra-abdominal adhesions, cerebrospinal fluid pseudocyst,
      or problems in retrieving dislocated catheters. From 6/1996 to 12/1997 we
      operated on twenty (20) children aged from 2-15 years (body weight 4.8-68 kg)
      with abdominal shunt insufficiency using the laparoscopy assisted technique. In
      only one case was it impossible to reach the abdominal cavity laparoscopically
      and conventional open surgery was necessary. We had no complications such as
      injured vessels or bowel and saw a complete recovery in all patients. In
      comparison to conventional surgery, we found handling simple, minor trauma to the
      patients, good intra-abdominal view, short operation times and good cosmetic
      results to be the advantages of laparoscopy-assisted abdominal shunt revision. In
      addition hospitalisation time can be reduced.

PMID- 9926331
TI  - Phase contrast MRI assessment of thoraco-lumbar spinal cord motion in spinal
      dysraphism.

PMID- 9926332
TI  - The microglial response in experimental infantile hydrocephalus.

PMID- 9926333
TI  - Outcome and clinical course of prenatally diagnosed cerebral ventriculomegaly.

PMID- 9926334
TI  - Neurological dysfunction above cele level in children with spina bifida cystica.

PMID- 9926335
TI  - Expression of cholecystokinin and somatostatin in the cortex of hydrocephalic and
      normal HTx rats.

PMID- 9926336
TI  - Shunt nephritis: fortuitous diagnosis and confirmation by serology (ASET).

PMID- 9926337
TI  - High prevalence of sensitization to inhalant allergens in patients with
      myelomeningocele allergic to latex products.

PMID- 9926338
TI  - Urolithiasis in spina bifida.

PMID- 9926339
TI  - A conceptual model of higher cortical function impairments in myelomeningocele.

PMID- 9926340
TI  - Prenatally detected mild/moderate cerebral ventriculomegaly: associated anomalies
      and outcome. Northern Congenital Abnormality Survey Steering Group.

PMID- 9926341
TI  - Laparoscopy-assisted pediatric reconstruction procedures.

PMID- 9926342
TI  - Outcome of prenatally detected mild/moderate cerebral ventriculomegaly.

PMID- 9926343
TI  - [Cognitive dysfunction in schizophrenia--new therapeutic possibilities. 11th
      ECNP. 31 October-4 November 1998, Paris].

PMID- 9926344
TI  - Childhood asthma.
AB  - OBJECTIVES: This article describes trends in the prevalence of asthma among
      children aged 0 to 14 from 1978/79 to 1994/95, and in hospital separations for
      asthma from 1974/75 to 1994/95. It also examines factors associated with
      childhood asthma. DATA SOURCES: Information on asthma among children aged 0 to 11
      is from the 1994/95 National Longitudinal Survey of Children and Youth (NLSCY),
      and among children aged 12 to 14, from the 1994/95 National Population Health
      Survey (NPHS). Hospital separation data are from the Hospital Morbidity File.
      Mortality data are from the Canadian Vital Statistics Data Base. ANALYTICAL
      TECHNIQUES: Prevalence estimates of asthma were calculated based on a sample of
      22,831 children aged 0 to 11 from the NLSCY and 637 children aged 12 to 14 from
      the NPHS. Logistic regression was used to estimate the odds of asthma among
      children aged 0 to 11 by selected characteristics. MAIN RESULTS: The prevalence
      of childhood asthma and hospital separations rates for asthma have increased
      sharply. A history of bronchitis and allergies, parental asthma, and residence in
      the Atlantic provinces and Quebec are associated with higher rates of asthma in
      children.

PMID- 9926345
TI  - Attitudes toward smoking.
AB  - OBJECTIVES: This article examines socio-demographic variations in attitudes about
      the health effects of smoking, second-hand smoke, and the importance of smoke
      free environments. DATA SOURCE: The data are from the Health file of the 1996/97
      cross-sectional provincial household component of the National Population Health
      Survey, conducted by Statistics Canada. The sample consists of 60,260 respondents
      aged 12 or older. ANALYTICAL TECHNIQUES: Three smoking attitudes scores were
      derived. Multivariate analyses were used to study how age, sex, educational
      attainment, province and smoking status were associated with attitude scores.
      MAIN RESULTS: Smokers placed less emphasis than non-smokers on the health risks
      associated with smoking. Older Canadians, particularly smokers aged 65 and older,
      tended to have more lenient attitudes toward smoking, compared with younger age
      groups. Respondents with high school education or less held more lenient
      attitudes, compared with those with a university degree. Quebec residents were
      more tolerant of tobacco use than were residents of other provinces.

PMID- 9926346
TI  - Work stress and health.
AB  - OBJECTIVES: This article describes work stress experienced by the employed
      population. It examines associations between job strain, job insecurity, physical
      demands, low co-worker support and low supervisor support, and four health
      outcomes: migraine, work injury, high blood pressure and psychological distress.
      DATA SOURCE: The data are from the household component of the 1994/95 National
      Population Health Survey conducted by Statistics Canada. Results are based on a
      sample of 9,023 employed Canadians aged 18 to 64. ANALYTICAL TECHNIQUES:
      Multivariate analyses were used to estimate associations between work stress and
      health problems, while controlling for other potential stressors. MAIN RESULTS:
      Among men, job strain was associated with migraine and psychological distress,
      and among women, with work injury. Job insecurity was associated with migraine
      among women. High physical demands were related to work injury in both sexes. Low
      co-worker support was related to migraine among men, and to work injury and
      psychological distress among women.

PMID- 9926347
TI  - Which workers smoke?
AB  - OBJECTIVES: This article examines differences by occupation in daily cigarette
      smoking prevalence and intensity among full-time workers, and how these
      differences are associated with smoking restrictions at work. DATA SOURCES: Most
      of the data are from a Health Canada-sponsored Supplement to the 1994/95 National
      Population Health Survey (NPHS). The analysis is based on 5,674 respondents aged
      15 to 64 who were full-time workers at the time of their interview. Comparable
      information is presented from the 1978/79 Canada Health Survey and the 1986
      Labour Force Survey Smoking Supplement. MAIN RESULTS: In 1994/95, 28% of full
      time workers were daily smokers, and about a third of them smoked 25 or more
      cigarettes a day. Smoking prevalence and intensity were lowest among white-collar
      workers and highest among blue-collar workers. Since 1978/79, there has been an
      overall decline in smoking prevalence, and since 1986, a decline in smoking
      intensity among all workers except those in outdoor blue-collar occupations.
      About 6 in 10 full-time workers who smoked daily encountered restrictions at
      work.

PMID- 9926348
TI  - Variations in angioplasty and bypass surgery.
AB  - OBJECTIVES: This article describes rates of and times to revascularization
      procedures for heart attack patients. DATA SOURCE: The data are from Statistics
      Canada's Person-Oriented Information Data Base. Hospital discharge records for
      heart attack patients were linked for fiscal years 1992/93 and 1993/94.
      ANALYTICAL TECHNIQUES: Hospital patients admitted between April 1 and September
      30, 1993 with a primary diagnosis of acute myocardial infarction (AMI) were
      followed for six months to determine what percentage underwent percutaneous
      transluminal coronary angioplasty and/or coronary artery bypass graft surgery.
      Analyses of time-to-procedure were performed for those patients who had not been
      hospitalized for AMI in the previous 12 months. MAIN RESULTS: Approximately
      24,000 Canadians were discharged from hospital during the first half of fiscal
      year 1993/94 with a diagnosis of AMI. Within six months, 8.7% had an angioplasty
      and 6.7% had a bypass; overall, 14.9% were revascularized. Women were less likely
      than men to have a bypass, but angioplasty rates did not differ significantly.
      The rate of revascularization declined with age. After adjusting for age and sex,
      rates were higher in the western provinces.

PMID- 9926349
TI  - Changes in stress and burden in families seeking therapy following traumatic
      brain injury: a follow-up study.
AB  - The current project is a preliminary investigation of changes in levels of
      distress and burden and family and marital adjustment in families following
      traumatic brain injury (TBI), replicating measures-used in the earlier Glasgow,
      TBI outcome research on relatives' stress and burden. Fifteen families (32
      individuals) seeking family counselling in a publicly funded family therapy
      centre were monitored over a two year period: prior to commencing counselling; 12
      months following the commencement of counselling; and 24 months following the
      commencement of counselling. The most significant and sustained changes in
      psychosocial outcome were a decrease in distress for both individuals with TBI
      and their carers as well as a reduction in relatives' burden and strain. Family
      conflict also reduced, just as family cohesion increased and adjustment within
      the family unit improved from pre-therapy to the time of follow-up 24 months
      later. However, reported levels of anger, despite significantly reducing during
      the first 12 months of the study, actually increased back to their original
      levels at the 24 month follow-up. Marital adjustment also worsened in the latter
      half of the study, with couples reporting a similar level of marital adjustment
      to that which they had experienced prior to counselling. These findings are
      discussed and recommendations made for more rigorous, controlled, longitudinal
      studies of the effectiveness of family therapy. It was also recommended that
      marital couples receive longer-term counselling to address their specific needs,
      and that the issue of anger be further investigated with a view to either
      reducing family members' anger, or bearing witness to the legitimacy of their
      anger in the longer-term, and assisting with anger-management programmes.

PMID- 9926350
TI  - Body image and patients with amputations: does the prosthesis maintain the
      balance?
AB  - This paper attempts to establish whether dissatisfaction with the artificial limb
      and/or body image relate to achieved mobility following lower limb amputation in
      established limb wearers. Patients attending limb fitting clinics (n = 107, 62%
      male, mean time from amputation 13.9 years; range 1-54) participated. The
      measures were a specially designed Attitude to Artificial Limbs Questionnaire, a
      Body Image Questionnaire adapted from an eating disorders instrument including
      reference to body shape, the Hospital Anxiety and Depression Scale and the Harold
      Wood Stanmore Mobility Scale. The rehabilitation physician rated prosthetic
      suitability on a Numerical Rating Scale. The results showed patients were
      moderately satisfied with their artificial limb, had little experience of body
      image disruption or distress and there was no overall relationship between these
      variables and mobility. However, those with a more negative body image were more
      anxious and in younger patients who sustained more traumatic than vascular
      amputations, the correlation between body image and mobility was significant,
      anxiety was higher and physician satisfaction with the prosthesis was lower. It
      is concluded that body image disruption, anxiety and depression are not common in
      established limb wearers except in young people with traumatic amputations.

PMID- 9926351
TI  - Quality of life: theory and methodology in rehabilitation.
AB  - Rehabilitation professionals understand and respect the specific life goals of
      people with disabilities. Rehabilitation efforts aim at facilitating their
      participation in rehabilitation activities that can promote their functional
      independence and lead to a better life quality ultimately. However, it is
      essential for the rehabilitation practitioners and researchers, through
      scientific studies, to identify factors that contribute to their client's quality
      of life on the basis of their assumptions, perceptions, goals, and values. Both
      culturally relevant theoretical foundation and measurement methodology are
      essential for the development of valid and reliable life quality measuring tools
      for rehabilitation programme evaluation.

PMID- 9926352
TI  - Spinal injury rehabilitation in Singapore.
AB  - Traumatic spinal cord injuries (SCI) are often preventable. In order to determine
      the characteristics and rehabilitation outcome of our spinal injured, we carried
      out a retrospective study of SCI patients admitted between January 1990 and
      December 1995 to the only spinal rehabilitation centre in Singapore. There was a
      total of 231 patients with ages between 14 and 82 years. The majority (73.6%)
      were below the age of 50. There was a male preponderance (83.1%) and a
      significant proportion of foreigners (20.3%). The most common causes of injuries
      were falls (50.7%) and road traffic accidents (37.2%). Damage to the cervical
      spine predominated (53.7%), followed by the thoracolumbar junction (23.4%). At
      the end of rehabilitation, the number of patients who were Frankel D/E improved
      significantly from 61 to 136. Sixty-eight patients were able to ambulate
      independently without aid and total independence in activities of daily living
      was achieved in 45 patients. The majority (87.9%) were discharged to their own
      homes. Of those who returned for follow-up, 86.3% were gainfully employed at the
      time of injury but only 21.6% had returned to some form of vocation within 1
      year.

PMID- 9926353
TI  - Mentoring in the context of a training programme for young unemployed adults with
      physical disability.

PMID- 9926354
TI  - Out-of-home placement of children with severe intellectual disabilities in
      Israel: research and implications.

PMID- 9926355
TI  - A field deceleration test to assess total wheelchair resistance.

PMID- 9926356
TI  - Diabetic amputation and long-term survival.

PMID- 9926357
TI  - Enhancing independent indoor travel and activity in a woman with multiple
      disabilities through special technology.

PMID- 9926358
TI  - Integration of unemployed persons with disabilities into the labour market in
      Slovenia.

PMID- 9926359
TI  - Analysis of speech disorders in acute pseudobulbar palsy: a longitudinal study of
      a patient with lingual paralysis.

PMID- 9926360
TI  - Antioxidant properties of bile salt micelles evaluated with different
      chemiluminescent assays: a possible physiological role.
AB  - The antioxidant activity of a representative series of free, glycine- and taurine
      conjugated bile acids was evaluated by two different chemiluminescent assays: (a)
      the enhanced chemiluminescence system based on horseradish peroxidase and
      luminol/oxidant/enhancer reagent, and (b) the hypoxanthine/xanthine
      oxidase/Fe(2+)-EDTA/luminol system. Bile acids were studied at final
      concentrations ranging from 1 to 28 mmol/L. All of the bile acids studied
      inhibited the steady-state chemiluminescent reaction and the extent of inhibition
      depended upon the structure of the bile acids, whereas the duration was related
      to bile acid concentration. The mechanism of the light inhibition is probably due
      to trapping of oxygen free radicals generated in the chemiluminescent reactions,
      within bile acid micelles. The free radicals trapped into micelles reduced the
      formation of luminol radicals and consequently the light output; when the
      micelles were saturated, the oxygen free radicals in solution again produced
      luminol radicals. The micelle interaction with reactive oxygen species could be a
      physiological mechanism of defence against the toxicity of those species in the
      intestinal content. On the other hand, alterations in bile acid organ
      distribution, concentration and composition leads to a membrane damage caused by
      their detergent-like properties, which could be associated to oxygen free radical
      production.

PMID- 9926361
TI  - A new screening method to detect water-soluble antioxidants: acetaminophen
      (Tylenol) and other phenols react as antioxidants and destroy peroxynitrite-based
      luminol-dependent chemiluminescence.
AB  - This study is based on a simple chemical interaction of peroxynitrite (O = N-O-O
      ) and luminol, which produces blue light upon oxidation. Since peroxynitrite has
      a half-life of about 1 s, a drug known as linsidomine (SIN-1) is used as a
      peroxynitrite generator. Peroxynitrite can oxidize lipids, proteins and nucleic
      acids. Upon the stimulation of inflammation and/or infection, macrophages and
      neutrophils can be induced to produce large amounts of peroxynitrite, which can
      oxidize phenols and sulphhydryl-containing compounds. Therefore, phenols and
      sulphhydryls eliminate peroxynitrite. This is an example of the Yin-Yang
      hypothesis e.g. oxidation-reduction. Acetaminophen (Tylenol) can inhibit fever
      and some types of pain without being a particularly effective anti-inflammatory.
      Since it is a phenol, it could act as a nitration target for peroxynitrite. Then
      peroxynitrite, the possible cause of pain and elevated temperature, might be
      destroyed in the reaction. Acetaminophen is a phenolic compound which produces a
      clear inhibitory dose-response curve with peroxynitrite in its range of clinical
      effectiveness. Whether acetaminophen actually works as we suggest is to be
      proven. Three different types of reaction could decrease the amount of
      peroxynitrite: (a) interference with base-catalysed opening of the SIN-1
      molecule; (b) destruction of one or both substances needed to form it--superoxide
      and/or nitric oxide; when the SIN-1 degrades to superoxide and nitric oxide, the
      former may be destroyed by superoxide dismutase (SOD); (c) peroxynitrite may
      react directly with phenols (mono-, di-, tri- and tetraphenols), possibly by
      nitration. Nordihydroguaiaretic acid and 2-hydroxyestradiol (catechol estrogen)
      are potent inhibitors of luminol light emission. Epineprine, isoproterenol,
      pyrogallol, catechol and ascorbic acid (a classic antioxidant) are all inhibitors
      of luminol chemiluminescence. Isoproterenol, norepinephrine/and epinephrine first
      inhibit light but overall stimulate the light production. Initially, SIN-1
      degrades to produce peroxynitrite, which reacts with luminol to produce blue
      light. If any of three catecholamines are present with the reaction that produces
      light, there is an initial inhibition of light production, and then a marked
      stimulation. A possible reason for this is that these catechols are oxidized and
      the metabolized phenol stimulates the production of light from luminol. Also,
      during oxidation of catecholamines superoxide is sometimes formed, which could
      stimulate production of peroxynitrite. This simple screening system is introduced
      to find useful antioxidants against peroxynitrite.

PMID- 9926362
TI  - Chemiluminescent assay of beta-D-galactosidase based on indole luminescence.
AB  - We developed a novel chemiluminescent assay of beta-D-galactosidase (beta-gal)
      based on the chemiluminescence of indole. 5-Bromo-4-chloro-3-indolyl-beta-D
      galactopyranoside (X-gal) was used as a substrate for beta-gal and also as a
      light emitter. X-gal was hydrolysed by beta-gal to liberate free indoxyl,
      followed by oxidation to indigo dye, and simultaneously produces hydrogen
      peroxide (H2O2). H2O2 reacts with the residual X-gal in the presence of
      horseradish peroxidase (HRP) to emit light. The measurable range of beta-gal
      obtained by this method was 6 x 10(-14) mol/L to 6 x 10(-11) mol/L; the detection
      limit was 3 amol/assay. This chemiluminescent assay could be applied to an enzyme
      immunoassay of thyroxine using beta-gal as the enzyme label.

PMID- 9926363
TI  - What do we measure with luminol-, lucigenin- and penicillin-amplified
      chemiluminescence? 1. Investigations with hydrogen peroxide and sodium
      hypochlorite.
AB  - Evidence is provided that the amplifiers luminol and lucigenin react with
      different reactive oxygen species (ROS), depending on the ROS-generating system
      used. H2O2 is used to produce calibration curves for luminol- and lucigenin
      amplified chemiluminescence. With this chemiluminescence generator we
      characterized the specificity and sensitivity of luminol- and lucigenin-amplified
      chemiluminescence and also studied penicillin G, a known enhancer of luminol
      amplified chemiluminescence. The combination of luminol and lucigenin in
      reciprocally changing concentrations is effective in an additive manner, but the
      weak amplifier penicillin increases luminol-amplified chemiluminescence
      distinctly more than in an additive manner in different combinations. Lucigenin
      amplified chemiluminescence is increased by penicillin at about 1% of the optimum
      concentration of penicillin; increasing concentrations of penicillin are less and
      less effective. On the other hand, low lucigenin concentrations enhance
      penicillin-amplified chemiluminescence at optimum penicillin concentrations more
      than in an additive manner. Fe2+ does not alter luminol-, lucigenin- or
      penicillin-amplified chemiluminescence. Co2+ increases luminol-amplified
      chemiluminescence by a factor of 100. Lucigenin- and penicillin-amplified
      chemiluminescence are minimally enhanced by Co2+. Cu2+ enhances luminol-amplified
      chemiluminescence with increasing concentrations by a factor of 1000. Lucigenin
      amplified chemiluminescence increases also by the factor of 1000, but the
      concentration-reaction curve is not as steep. NaOCl enhances H2O2/Fe(2+)-driven
      luminol-amplified chemiluminescence in a concentration-dependent manner by a
      factor of 10(4) (in the highest concentration of 10 mmol/L) and lucigenin
      amplified chemiluminescence only by a factor of about 25. Catalase (CAT)
      abolishes luminol-, lucigenin- and penicillin-amplified chemiluminescence
      completely, whereas superoxide dismutase (SOD) has no effect on luminol- or
      penicillin-amplified chemiluminescence, but enhances lucigenin-amplified
      chemiluminescence five-fold increasingly with increasing SOD activity.

PMID- 9926364
TI  - LuxR controls the expression of Vibrio fischeri luxCDABE clone in Escherichia
      coli in the absence of luxI gene.
AB  - We have recently suggested that the expression of V. fischeri right lux operon is
      initiated from two sites, the first located upstream of the luxI gene, while the
      second seems to be located upstream of the luxC gene. The transcription from both
      sites is negatively controlled by H-NS protein. E. coli MC4100 rpoS hns mutant
      harbouring the V. fischeri luxCDABE genes showed constitutive mode and 70,000
      fold higher luminescence than the wild-type cells. The present study shows that
      the expression of luxCDABE genes in E. coli MC4100 wild-type cells is also
      controlled by LuxR protein in the absence of the autoinducer. The co-presence of
      a ptac-controlled luxR gene in a trans position to a plasmid carrying the
      luxCDABE genes resulted in 100,000 times higher luminescence. In the absence of
      the autoinducer, the presence of the luxR gene under its own regulated control
      resulted in about 100-200-fold increase of luminescence from the luxC upstream
      site. Taken together, it seems that the LuxR protein initiates the formation of
      the V. fischeri lux system cloned in E. coli from two sites located upstream and
      downstream of the luxI gene. Only the activation of the first site requires the
      presence of the autoinducer, whereas the second site is fully activated by LuxR
      protein in the absence of the autoinducer.

PMID- 9926365
TI  - Immobilization of luciferase from a firefly lantern extract on glass strips as an
      alternative strategy for luminescent detection of ATP.
AB  - The bioluminescent reaction catalysed by firefly luciferase has become widely
      established as an outstanding analytical system for assay of ATP. When used in
      solution, luciferase is unstable and cannot be re-used, a problem that can be
      partially circumvented by immobilizing the enzyme on solid substrates.
      Transparent glass is especially advantageous over alternative immobilizing
      matrices, since it allows most of the emitted photons to be detected. We report a
      new method for luciferase immobilization on glass which does not require prior
      silanization and glutaraldehyde activation, thus saving preparation time and
      minimizing enzyme inactivation. Our method is based on the co-immobilization by
      adsorption of luciferase (from a firefly lantern extract) and poly-L-lysine (PL)
      on non-porous glass strips. Luciferase immobilized in this way exhibits minimal
      variations in intersample activity, high sensitivity for ATP detection (linear
      luminescence responses down to 50 nmol/L) and good stability (full activity for
      at least 60 days when stored at -80 degrees C). PL-mediated immobilization of
      luciferase on glass strips provides an attractive strategy for the design of
      specific ATP biosensors, with potential in industry, environmental screening,
      medicine and biological research.

PMID- 9926366
TI  - More on immunizations.

PMID- 9926367
TI  - T. Duckett Jones and his criteria for the diagnosis of acute rheumatic fever.

PMID- 9926368
TI  - A pediatrician's view. Asthma: something is wrong.

PMID- 9926369
TI  - Childhood asthma: we can do better!

PMID- 9926370
TI  - Management of acute asthma in the pediatric office.

PMID- 9926371
TI  - Symptom monitoring in childhood asthma: how to use a peak flow meter.

PMID- 9926372
TI  - Management of chronic childhood asthma in the primary care office.

PMID- 9926373
TI  - The asthma specialist: when and why to refer the pediatric patient.

PMID- 9926374
TI  - Improving the care of children with asthma in pediatric practice: the HIPPO
      project. Helping Improve Pediatric Practice Outcomes.

PMID- 9926375
TI  - Asthma in managed care.

PMID- 9926376
TI  - Resident's column: all that wheezes.... The challenges of a common pediatric
      disease.

PMID- 9926377
TI  - Family planning programs: improving quality.

PMID- 9926379
TI  - Pedicle instrumentation in the thoracic spine. A morphometric and cadaveric study
      for placement of screws.
AB  - STUDY DESIGN: In part 1 of the study, the morphometry of thoracic pedicles and
      bony landmarks for pedicle screw placement were evaluated. In part 2, pedicle
      screws were inserted in fresh cadavers, using a different entry point in the left
      and right pedicles. OBJECTIVES: To identify the safest entry point and screw
      orientation for pedicle screws in the thoracic spine. SUMMARY OF BACKGROUND DATA:
      A few morphometric investigations have been performed on thoracic vertebrae, but
      the safest technique for screw insertion in thoracic pedicles has not been
      analyzed. METHODS: Mean, range, and standard deviations of pedicle transverse
      diameter and pedicle orientation were measured in 99 dried thoracic vertebrae. We
      evaluated the position of the bottom of the superior facet and that of the
      superior border of the transverse process in relation to the center of the
      pedicle. The relation between the pedicle axis and the superior facet in the
      frontal plane was also assessed. In part 2 of the study, pedicle screws were
      inserted in fresh cadavers at the intersection between the superior border of the
      transverse process and the middle of the superior facet (entry point A) and
      between the former and the lateral two thirds of the facet (entry point B).
      RESULTS: The smallest transverse diameter was found at 16 (mean 4.3 mm) where
      pedicles measured less than 5 mm in 68% of the specimens. In the frontal plane,
      the pedicle axis intersected the middle of the superior facet in 15% of
      specimens, the lateral two-thirds in 62%, and the lateral border of the facet in
      23%. Of the 126 screws inserted in fresh human cadavers, 15 (24%) of the screws
      inserted using entry point A and 10 (16%) of those inserted using entry point B
      violated the pedicle cortex (P > 0.05). Six (10%) of the screws inserted using
      entry point A compared with no screw inserted using entry point B penetrated the
      anterior vertebral cortex (P = 0.03). CONCLUSIONS: Pedicles between T4 and T8 may
      not be wide enough for screw fixation. An entry point for pedicle screws located
      at the intersection between the superior border of the transverse process and the
      lateral two thirds of the superior facet seems more likely to be in line with the
      pedicle axis than do other entry points. In the lower thoracic vertebrae this
      entry point, in combination with insertion of the screws more medially oriented
      than the pedicle axis, significantly reduces the risk of violating the anterior
      vertebral cortex.

PMID- 9926378
TI  - The quantitative anatomy of the laminas of the spine.
AB  - STUDY DESIGN: This study evaluated the dimensions of the laminas from C2 to L5
      using adult spine specimens. OBJECTIVES: To provide a set of quantitative data
      for the laminas from C2 to L5. SUMMARY OF BACKGROUND DATA: Anatomic evaluation of
      the pedicle and facet joint in the spine has been extensively reported. No
      detailed studies of the laminas from the cervical to the lumbar spines exist.
      METHODS: Thirty-seven spines from C2 to L5 were directly evaluated for this
      study. Anatomic evaluation of the laminas included the laminar height, width,
      thickness, and angulation. RESULTS: In general, the measurements were greater in
      male specimens than in female specimens, although significant differences (P <
      0.05) between male and female specimens were noted in only three measurements.
      The greatest laminar height was at T11 (25.1 +/- 2.5 mm), and the least was at C4
      (10.4 +/- 1.1 mm). The greatest laminar width was at L5 (15.7 +/- 2.0 mm), and
      the least was at T4 (5.8 +/- 0.8 mm). Laminar widths in the cervical region were
      slightly more than those in the thoracic region. The greatest laminar thickness
      was at T2 (5.0 +/- 0.2 mm), whereas the least was at C5 (1.9 +/- 0.6 mm). Laminar
      thickness tended to increase in the upper thoracic region and to decrease
      slightly in the lower thoracic region. The mean laminar thickness of the lower
      cervical region was least in the whole spine. The widest angle was at C3 (116.1
      +/- 8.8 degrees) and T7 (112.3 +/- 8.0 degrees) and the narrowest was at C2 (99.1
      +/- 8.0 degrees) and L3 (99.9 +/- 6.3 degrees). The slope angles of the laminas
      varied from 97.8 +/- 3.0 degrees at T9 to 129.0 +/- 7.5 degrees at L3.
      CONCLUSIONS: Surgical placement of sublaminar instruments may benefit from this
      quantitative study through the use of the provided anatomic parameters of the
      laminas.

PMID- 9926380
TI  - A comparative study of chemonucleolysis with recombinant human cathepsin L and
      chymopapain. A radiologic, histologic, and immunohistochemical assessment.
AB  - STUDY DESIGN: Investigation of the effects of recombinant human cathepsin L on
      intervertebral discs and comparison with the effects of chymopapain. OBJECTIVE:
      To evaluate the effects of cathepsin L on intervertebral discs as an agent for
      chemonucleolysis. SUMMARY BACKGROUND DATA: Cathepsin L is a typical cysteine
      proteinase that belongs to the papain superfamily. It plays a major role in
      intracellular proteolysis and is not believed to induce anaphylactic reactions.
      METHODS: In vivo: Rabbit intervertebral discs were injected with recombinant
      human cathepsin L, its buffer solution, and chymopapain. After 1, 4, and 16 weeks
      the animals were killed, and radiologic and histologic examinations were
      performed. In vitro: The enzymatic actions of recombinant human cathepsin L and
      chymopapain on human intervertebral disc proteoglycans were examined
      immunohistochemically using antiproteoglycan antibodies. RESULTS: In rabbit
      models, roentgenography showed that disc spaces treated with cathepsin L and
      chymopapain had become narrower 1 week after injection. Histologically, loss of
      safranin-O staining was observed in the anulus fibrosus of discs treated with
      cathepsin L. After 16 weeks, nucleus pulposus had regenerated with chondrocyte
      like cells, and the safranin-O staining characteristics of the matrix also had
      recovered. In an immunohistochemical study, all components of the proteoglycan
      stained weakly after chymopapain digestion. After cathepsin L digestion,
      unsulfated chondroitin and core protein staining was weaker, but the chondroitin
      6-sulfate staining was unaffected. CONCLUSIONS: Cathepsin L seems to be an
      effective agent for chemonucleolysis. Its enzymatic action on proteoglycan
      appears to be different from that of chymopapain.

PMID- 9926381
TI  - A study of adenosine treatment in experimental acute spinal cord injury. Effect
      on arachidonic acid metabolites.
AB  - STUDY DESIGN: A prospective, randomized, blinded experimental trauma study. STUDY
      OBJECTIVE: The effect of adenosine on arachidonic acid metabolites and lipid
      peroxidation was investigated in induced spinal cord injury. SUMMARY OF
      BACKGROUND DATA: Effects of adenosine in ischemia-reperfusion models have been
      studied, but no studies of adenosine's effect on direct trauma to the spinal cord
      have been reported. METHODS: Thirty-seven adult Wistar albino rats were randomly
      divided into four groups and underwent laminectomy. Group 1 underwent a sham
      operation. Group 2 received an intravenous adenosine infusion of 100
      micrograms/kg per minute for 30 minutes. In Group 3, a standard spinal cord
      trauma of 50 g.cm strength was established at the lower thoracic level with a
      "weight-drop" technique, and Group 4 received an infusion of adenosine (100
      micrograms/kg per minute) for 30 minutes after the trauma. RESULTS: Tissue
      prostaglandin E2 activity was significantly higher in adenosine-treated trauma
      groups when compared with that in other groups (P < 0.0001). The difference in
      tissue leukotriene C4 activity between control and trauma groups was significant
      (P < 0.05). Adenosine infusion after trauma limited the increases in lipid
      peroxidation, with the difference approaching significance at P = 0.06. The
      structure of myelin was well preserved in the adenosine-treated trauma group.
      However, the changes were irreversible in severely damaged areas. CONCLUSION:
      After acute spinal cord trauma, intravenous adenosine infusion of 100
      micrograms/kg per minute could attenuate progression to secondary injury, but
      adenosine alone was not effective yet.

PMID- 9926382
TI  - Epidural abscess of the cervical spine with osteomyelitis of the odontoid
      process.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To document the rare condition of
      staphylococcal osteomyelitis of the odontoid process and to increase knowledge
      about the clinical characteristics and favorable outcome if patients are managed
      appropriately. SUMMARY OF BACKGROUND DATA: Osteomyelitis of the odontoid process
      caused by Staphylococcus aureus is a rare disease. A handful of cases have been
      reported within the last 30 years. Destructive odontoid peg involvement is most
      commonly associated with rheumatoid disease, which has a distinct clinical course
      compared with that of bacterial infection. METHODS: Two patients with bacterial
      osteomyelitis of the odontoid peg underwent medical and surgical treatment. They
      were observed for 3 years. All authors were involved in the care of these
      patients. RESULTS: Close monitoring of the patients' neurologic status and the
      use of noninvasive imaging techniques to evaluate the cervical spine led to an
      individualized treatment plan including antibiotic medication and transoral
      surgery with good outcomes in both cases. CONCLUSIONS: Awareness of the
      occurrence of bacterial osteomyelitis of the odontoid process, with or without
      neurologic symptoms, in patients with neck pain and fever may lead to earlier
      detection of this potentially critical condition, which has an excellent
      prognosis when treated early and appropriately.

PMID- 9926383
TI  - Cervical root compression monitoring by flexor carpi radialis H-reflex in healthy
      subjects.
AB  - STUDY DESIGN: One-group, pretest-postest experimental research with repeated
      measures. OBJECTIVE: To determine the effect of head postural modification on the
      flexor carpi radialis H-reflex in healthy subjects. SUMMARY OF BACKGROUND DATA: H
      reflex testing has been reported to be useful in evaluating and treating patients
      with lumbosacral and cervical radiculopathy. The idea behind this technique is
      that postural modification can cause further H-reflex inhibition, indicating more
      compression of the impinged nerve root, or recovery, indicating decompression of
      the root. Such assumptions cannot be supported unless the influence of normal
      head postural modification on the H-reflex in healthy subjects is studied.
      METHODS: Twenty-two healthy subjects participated in this study (14 men, 8 women;
      mean age, 39 +/- 9 years). The median nerve of the subjects at the cubital fossa
      was electrically stimulated (0.5 msec; 0.2 pulses per second [pps] at H-max),
      whereas the flexor carpi radialis muscle H-reflex was recorded by
      electromyography. The H-reflexes were recorded after the subject randomly
      maintained the end range of head-forward flexion, backward extension, rotation to
      the right and the left, lateral bending to the right and the left, retraction and
      protraction. These were compared with the H-reflex recorded during comfortable
      neutral positions. Data were recorded after the subject maintained the position
      for 30 seconds, to avoid the effect of dynamic postural modification on the H
      reflex. Four traces were recorded in each position. During recording, the H
      reflex was monitored by the M-response to avoid any changes in the stimulation
      recording condition. RESULTS: Repeated multivariate analysis of variance was used
      to evaluate the significance of the difference among the H-reflex, amplitude, and
      latency, in various head positions. The H-reflex amplitude showed statistically
      significant changes (P < 0.001) with head postural modification. All head
      positions, except flexion, facilitated the H-reflex. Extension, lateral bending,
      and rotation toward the side of the recording produced higher reflex facilitation
      than the other positions. These results indicate that H-reflex changes may be
      caused by spinal root compression-decompression mechanisms. It may also indicate
      that relative spinal root decompression occurs in most head-neck postures except
      forward flexion. CONCLUSIONS: Head postural modification significantly influences
      the H-reflex amplitude but not the latency. This indicates that the H-reflex is a
      more sensitive predictor of normal physiologic changes than are latencies. The H
      reflex modulation in various head positions may be-caused by relative spinal root
      compression-decompression mechanisms.

PMID- 9926384
TI  - Ossification of the posterior longitudinal ligament of the spine. A case-control
      risk factor study.
AB  - STUDY DESIGN: A case-control study. OBJECTIVES: To determine the risk factors for
      ossification of the posterior longitudinal ligament (OPLL) of the spine. SUMMARY
      OF BACKGROUND DATA: Previous epidemiologic studies conducted in Japan showed
      consuming vegetable protein and salt was a risk factor for OPLL. Dietary habits
      of the Taiwanese and Japanese people are similar. Whether the similar dietary
      habits play an important role in the high prevalence of OPLL in Taiwan was of
      interest. METHODS: A case-control study was conducted in a tertiary teaching
      hospital. The study included 98 consecutive cervical spine patients with OPLL,
      with 98 age-matched patients with cervical spondylosis serving as control
      subjects. Radiologic examinations, clinical interviews, physical examinations,
      and risk factor questionnaires were administered to all the participants.
      RESULTS: Compared with incidence in the control patients, the frequency of the
      ossification of the anterior longitudinal ligaments was significantly higher in
      OPLL patients with OPLL (31% vs. 19%; P = 0.049), but there was no difference in
      incidence of ossification of the ligamentum flavum (13.3% vs. 16.3%; P = 0.546).
      More OPLL patients preferred a high-salt diet (OPLL/CS, no:somewhat:yes =
      23/38:18/25:57/35;, X2 for trend = 6.3; P = 0.001) and pickled foods (OPLL/CS,
      no:somewhat:yes = 39/56:11/11:48/31; X2 for trend = 6.7; P = 0.0099). Fewer
      patients with OPLL consumed meat daily (63% vs. 79%; P = 0.018). High-salt diet
      (odds ratio = 2.62) and daily meat intake (odds ratio = 0.39) showed persistent
      association with OPLL in a multivariate logistic regression. CONCLUSIONS: The
      similar dietary habits, particularly a high-salt and low meat intakes, may
      partially explain the high prevalence of OPLL in Taiwan and Japan. Modifying
      dietary habits may help prevent this disease, especially in those high-risk
      populations.

PMID- 9926386
TI  - Motor-evoked potentials elicited from human erector spinae muscles by
      transcranial magnetic stimulation.
AB  - STUDY DESIGN: The compound muscle action potentials elicited from the erector
      spinae muscles by transcranial magnetic stimulation was studied in 15 healthy
      adults. OBJECTIVE: To describe the recording procedure for consistent compound
      muscle action potentials elicited from the human erector spinae by transcranial
      magnetic stimulation and to establish the normal latency ranges of the responses,
      at respective spinal levels, for the practical use of this test. SUMMARY OF
      BACKGROUND DATA: Although recording of the compound muscle action potentials from
      limb muscles after transcranial magnetic stimulation has been extensively
      studied, the use of the erector spinae as the target muscle has not, probably
      because of the difficulty of consistently evoking compound muscle action
      potentials. METHODS: Compound muscle action potentials from the erector spinae
      muscles were recorded with the subject prone during tonic voluntary background
      contraction of the back extensor muscles at approximately 20% of maximum effort.
      The compound muscle action potentials were recorded concurrently at multiple
      levels after magnetic stimulation to the brain with a round coil centered over
      the vertex. RESULTS: The onset and peak latencies (mean +/- SD) of the major
      negative potential increased progressively toward the caudal level from 13.4 +/-
      2.2 msec and 17.6 +/- 2.2 msec at T5-T6 to 20.8 +/- 1.5 msec and 26.3 +/- 3.0
      msec at L4-L5 in healthy subjects. The latencies changed significantly between
      two adjacent segments from T5-T6/T6-T7 through T12-L1/L1-L2. CONCLUSIONS: The
      compound muscle action potential was elicited from the voluntarily contracted
      erector spinae at all spinal levels from T5-T6 through L4-L5 in all subjects
      tested. This noninvasive test has potential for evaluating the functional
      integrity of the motor pathway in the thoracic spinal cord, the spinal nerves, or
      both.

PMID- 9926385
TI  - Electromyographic responses of back and limb muscles associated with spinal
      manipulative therapy.
AB  - STUDY DESIGN: Ten young, asymptomatic male subjects underwent 11 clinically
      relevant spinal manipulative treatments along the length of the spine to test the
      magnitude and extent of reflex responses associated with the treatments.
      OBJECTIVES: To determine the magnitude and extent of reflex responses elicited by
      spinal manipulative treatments. SUMMARY OF BACKGROUND DATA: Spinal manipulative
      treatments have been associated with a reflexogenic relief of pain and a loss of
      hypertonicity in muscles within the treatment area. However, there is no study in
      which results show the probability of occurrence or the extent of reflex
      responses during spinal manipulative treatments. METHODS: Asymptomatic subjects
      received spinal manipulative treatments on the cervical, thoracic, and lumbar
      levels and on the sacroiliac joint. Reflex activities were measured using 16
      pairs of bipolar surface electrodes placed on the back and proximal limb
      musculature. The percentage of occurrence and the extent of reflex responses in
      the back and proximal limb musculature were determined. RESULTS: Each treatment
      produced consistent reflex responses in a target-specific area. The reflex
      responses occurred within 50-200 msec after the onset of the treatment thrust and
      lasted for approximately 100-400 msec. The responses were probably of
      multireceptor origin and were elicited asynchronously. CONCLUSIONS: This is the
      first study in which results show a consistent reflex response associated with
      spinal manipulative treatments. Because reflex pathways are evoked systematically
      during spinal manipulative treatment, there is a distinct possibility that these
      responses may cause some of the clinically observed beneficial effects, such as a
      reduction in pain and a decrease in hypertonicity of muscles.

PMID- 9926387
TI  - Computed tomographic and magnetic resonance imaging of chronic odontoid
      fractures.
AB  - STUDY DESIGN: The analysis of the imaging characteristics found in chronic
      odontoid fractures. OBJECTIVES: To determine the efficacy of computed tomography
      and magnetic resonance imaging in diagnosing a chronic odontoid fracture. SUMMARY
      OF BACKGROUND DATA: Radiographic examination of the cervical spine is intrinsic
      to the evaluation of all patients with blunt trauma. Injury to the craniocervical
      junction constitutes 19-25% of all cervical spine fractures. At the authors'
      trauma center computed tomography is routinely used instead of the open-mouth
      odontoid radiograph to facilitate cervical spine evaluation. This practice has
      increased the detection of fractures that are unrecognized in plain radiography,
      and has, at the same time, raised questions about the age and significance of
      these fractures. METHODS: Radiography, computed tomography, and magnetic
      resonance imaging studies were performed on three patients who came to the
      emergency department with odontoid fractures. Two patients had a history of
      severe trauma, and one had a history inconsistent with an acute odontoid
      fracture. One patient also had a technetium Tc 99m methylene dihydroxyphosphonate
      bone scan. The studies were obtained to determine the age of the fractures.
      RESULTS: All three patients were determined to have chronic odontoid fractures.
      This diagnosis was facilitated by the use of computed tomographic and magnetic
      resonance imaging. Computed tomography showed increased sclerosis in the proximal
      fracture fragment in all cases and well-corticated fracture edges in one patient.
      Magnetic resonance images showed normal bone marrow or bone sclerosis in the
      odontoid process. Soft tissue edema was absent. A bone scan was not useful in
      resolving this issue. CONCLUSION: Computed tomography and magnetic resonance
      imaging can be useful in determining the chronicity of an odontoid fracture.

PMID- 9926388
TI  - Dynamic motion analysis of normal and unstable cervical spines using
      cineradiography. An in vivo study.
AB  - STUDY DESIGN: Cervical motion patterns were analyzed in a normal population and
      in patients with cervical instability by using cineradiography. OBJECTIVES: To
      determine normal and pathologic motion patterns in the cervical spine through an
      in vivo continuous motion analysis. SUMMARY OF BACKGROUND DATA: Cineradiographic
      techniques have been used in a limited number of studies to quantify spinal
      motion. There is a paucity of information regarding dynamic motion patterns in
      normal and pathologic cervical spines. METHODS: Ten healthy subjects and 12
      patients with unstable cervical spines (C1-C2 subluxation caused by rheumatoid
      arthritis, n = 10; instability below C2, n = 2) were studied. Cervical motion
      during flexion from the maximum extension position was recorded using
      cineradiography. Cervical segmental motions (C1-C2 to C5-C6) were continuously
      measured through quantifying cineradiographic images projected on a digitizer.
      RESULTS: Normal cervical spines showed a well-regulated stepwise motion pattern
      that initiated at C1-C2 and transmitted to the lower segments with time lags.
      Pathologic spines showed a different order of onset of segmental motion. In
      patients with rheumatoid arthritis who had atlantoaxial subluxation, C1-C2 motion
      initiated significantly earlier than C2-C3 motion. In patients with segmental
      instability below C2, motion in the unstable segments preceded that in the upper
      intact segments. CONCLUSIONS: Different motion patterns were observed between
      normal and pathologic cervical spines. Cineradiographic motion analysis is a
      valuable adjunctive technique, especially in diagnosis or evaluation of
      conditions that cannot be identified through conventional radiographic
      examination.

PMID- 9926389
TI  - The spinal curve in standing and sitting postures in children with idiopathic
      scoliosis.
AB  - STUDY DESIGN: A sample of convenience of children with moderate idiopathic
      scoliosis without bracing or surgery was studied. The sample consisted of 19
      children, aged 9 to 16 years, with mean Cobb angle of 24 degrees. The spinal
      configurations and paraspinal muscle activity in several commonly assumed
      postures were examined. OBJECTIVES: To determine how the apex angles, verticality
      of spine, and muscle activity vary with the assumed posture and whether the
      location and the number of spinal curves affect these variables. SUMMARY OF
      BACKGROUND DATA: It has been suggested that the configuration of the spine in
      commonly assumed postures can affect the spinal curve in scoliosis because of
      gravitational bending moments. There is, however, a paucity of data obtained in
      subjects in sitting postures that school-age children assume daily for prolonged
      periods. Absence of bilateral symmetry in pressure during sitting has been
      described, but its effect on the spinal apex angle has not been investigated.
      METHODS: Infrared-emitting markers, whose three-dimensional positions could be
      tracked by a pair of cameras, were affixed to the spine. The natural postures
      studied were relaxed standing, relaxed sitting, erect sitting, and writing while
      seated. Electromyographic activity in muscles close to the spinal apexes was
      recorded bilaterally for each test posture. RESULTS: Subjects leaned laterally
      and, in general, anteriorly, in all test postures, rather than placing the C7
      vertebra vertically above S1. The direction of lean and the change in the spinal
      apex angle from standing to sitting varied depending on whether the spinal curve
      was single or double, thoracic or lumbar. Subjects with single curves, whether
      thoracic or lumbar, tended to lean laterally toward the convexity of their curve
      apex--that is, the lean was in a direction that reduced the apex angle. Subjects
      with double curves (thoracic and lumbar), in all postures except relaxed sitting,
      tended to lean toward the convexity of the lumbar curve, thereby reducing the
      lumbar apex angle and exacerbating the thoracic angle. Most subjects' apex angles
      were smaller in relaxed or erect sitting than in relaxed standing.
      Electromyographic activity was in general greater on the convex side of the
      curve, with greatest activity in erect sitting. CONCLUSIONS: The findings
      indicate that in self-selected postures the gravitational effect of leaning and
      the muscle activity in paraspinal muscles may serve to reduce the apex angle.
      Thus, a fully upright, centered posture may not be best for correction of every
      patient's spinal curve.

PMID- 9926390
TI  - Outcomes of disabling cervical spine disorders in compensation injuries. A
      prospective comparison to tertiary rehabilitation response for chronic lumbar
      spinal disorders.
AB  - STUDY DESIGN: A prospective, longitudinal cohort study assessing quantitative
      socioeconomic outcomes of tertiary rehabilitation for chronically disabled
      patients with cervical spinal disorders compared with those with more common
      chronic lumbar spinal disorders. OBJECTIVES: To assess 1-year socioeconomic
      outcomes of a worst-case cohort of consecutive patients with chronic cervical
      spinal disorders compared with those of patients with lumbar spinal disorders and
      to assess differences in an array of variables between those patients who
      reported any period of work during the posttreatment year and those who did not.
      SUMMARY OF BACKGROUND DATA: Few investigators have evaluated outcomes in patients
      with cervical spinal disorders. None have specifically studied distinctions in
      socioeconomic outcomes in patients with chronic cervical spinal disorders and in
      patients with other spinal disorders. Reports of pain are noted to persist in a
      high percentage of patients with whiplash receiving compensation even 10 years
      after injury, but the status of work, use of health care resources, financial
      disputes, or recurrent injury are unknown. METHODS: A cohort of consecutive
      chronically disabled patients with spinal disorders (N = 1198) was assessed for
      prospectively collected demographic, self-report, and physical performance data.
      A subset of patients (n = 421) with work-related cervical spinal disorders was
      compared with a group with various lumbar spinal disorders (n = 777). A
      structured clinical interview was administered 1 year after patients entered an
      interdisciplinary functional restoration program. RESULTS: High rates of return
      to work and continuation of work were recorded in the cervical and lumbar spinal
      disorder groups, with low rates of recurrent injury, new surgery in the injured
      area, and use of health care resources. There were no statistically significant
      differences between the groups. Multivariate analyses showed several variables
      that differentiated between those patients who had any reported period of work
      during the post-treatment year versus those who did not in the cervical and the
      lumbar spinal disorder groups. CONCLUSIONS: This first large cohort study of
      outcomes in chronically disabled patients with work-related cervical spinal
      disorder produced results similar to those found in tertiary functional
      restoration rehabilitation in chronic lumbar spinal disorders. In spite of poor
      outcomes reported in the literature for similar cervical and lumbar spinal
      disorders in patients receiving workers' compensation for disability, successful
      outcomes can be anticipated after effective rehabilitation, regardless of
      response to prerehabilitation treatment.

PMID- 9926391
TI  - Traumatic open anterior lumbosacral fracture dislocation. A report of two cases.
AB  - STUDY DESIGN: Case presentation. OBJECTIVES: To review the diagnosis and
      treatment of rare anterior lumbosacral fracture dislocations. SUMMARY OF
      BACKGROUND DATA: The severity of closed anterior and open and closed posterior
      lumbosacral dislocations has been documented; however, there have been no reports
      of open anterior lumbosacral dislocations in the literature. Two patients are
      reported who experienced acute open anterior lumbosacral fracture dislocations.
      METHODS: Review of the patient history and physical examination, radiologic
      review, operative techniques, and a review of the literature. RESULTS: Fractures
      healed in both patients, with no major infections. Both patients had persistent
      neurologic deficits at last follow-up. CONCLUSIONS: Open lumbosacral fracture
      dislocations are complex injuries that require diligence on the part of the
      surgeons involved the recognize the severity of the injury, to prevent or resolve
      any infectious process, to prevent further neurologic injury, and then to obtain
      and maintain alignment of the spine on the pelvis.

PMID- 9926392
TI  - Severe kyphosis secondary to glucocorticoid-induced osteoporosis in a young adult
      with Cushing's disease. A case report and literature review.
AB  - STUDY DESIGN: A case report and literature review of thoracic hyperkyphosis
      deformity secondary to glucocorticoid-induced osteoporosis in Cushing's disease.
      OBJECTIVES: To identify the pathophysiology of glucocorticoid-induced
      osteoporosis and to outline the diagnosis and treatment options for a patient
      with severe spinal deformity secondary to unrecognized excess glucocorticoid
      activity. SUMMARY OF BACKGROUND DATA: Glucocorticoid-induced osteoporosis is seen
      in patients exposed to supraphysiologic levels of endogenous or exogenously
      administered glucocorticoids. In these patients, glucocorticoids act to suppress
      bone formation and increase bone resorption by indirect and direct effects. These
      patients have a high prevalence of trabecular bone loss, resulting in much higher
      rates of vertebral body collapse and pathologic fracture and thus causing an
      increased propensity toward kyphotic spinal malalignment. METHODS: The literature
      was reviewed and case reports studied. This case report highlights the
      pathophysiology of the disease process that caused the spinal deformity and the
      surgical intervention used to correct the kyphotic deformity after the metabolic
      problem was resolved. RESULTS: This patient has responded well to treatment and
      surgical intervention to correct a thoracic hyperkyphotic deformity without
      complication. CONCLUSIONS: Unrecognized endogenous production of glucocorticoids
      in Cushing's disease should be considered in young adult patients with
      progressive osteoporotic spinal deformities.

PMID- 9926393
TI  - Congenital scoliosis with posterior spinal arthrodesis T2-L3 at age 3 years with
      41-year follow-up. A case report.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To document the long-term effects of
      early fusion for progressive congenital scoliosis. SUMMARY OF BACKGROUND DATA:
      There is concern about fusion at an early age causing torso shortening and
      possible crankshaft phenomenon. METHODS: A review of medical and radiologic
      records. RESULTS: A 3-year old girl with progressive congenital scoliosis had
      posterior spinal arthrodesis in 1955. A pseudarthrosis was repaired at age 4, and
      at age 8 she had an osteotomy of the fusion mass because of bending of the fusion
      mass. In a follow-up 41 years after fusion, she has no back pain and no history
      of pulmonary problems. Despite the long fusion at a young age, her torso-to-leg
      ratio was remarkably good. The thoracic lordosis had improved to a normal
      thoracic kyphosis. CONCLUSION: Early arthrodesis was life saving and caused no
      long-term problems. Because significant spinal growth has occurred by age 3, no
      adverse effects on torso-leg ratio with an early long arthrodesis, and in
      addition the crankshaft phenomenon is rare in congenital scoliosis.

PMID- 9926394
TI  - Unknown case.

PMID- 9926395
TI  - Measured external curves and surface electromyograms in patients with mild
      untreated scoliosis.

PMID- 9926396
TI  - Sequence and expression in Escherichia coli of the coat protein gene of the
      dwarfing strain of soybean dwarf luteovirus.
AB  - The nucleotide sequence of the coat protein gene of the dwarfing (D) strain of
      soybean dwarf luteovirus (SbDV) was determined from cloned cDNA. The gene
      contains 600 nucleotides and encodes a protein of 200 amino acids with a
      calculated molecular mass of 22.2 kDa. A major portion of the coat protein open
      reading frame (ORF) was expressed in Escherichia coli as a pET fusion protein and
      the product was detected by western blot analysis using SbDV-D polyclonal
      antibodies. Comparison of the deduced coat protein amino acid sequence to that
      from the yellowing (Y) strain of SbDV demonstrated 88% identity.

PMID- 9926397
TI  - Molecular cloning and nucleotide sequence of 3'-terminal region of classical
      swine fever virus LPC vaccine strain.
AB  - A cDNA of the 3'-terminus of classical swine fever virus (LPC vaccine strain) was
      cloned and sequenced. The 3431 nucleotides and deduced amino acid sequences were
      compared with those of other pestiviruses, and the similarity of nucleotide
      sequences and deduced amino acid sequences were found to be 84-95% and 95-98%,
      respectively. Similar to other isolates of classical swine fever virus, the
      sequenced region included the non-structural gene p58 (NS5A) and part of p76
      (NS5B) gene. The p76 gene of LPC vaccine strain also contained a highly conserved
      motif G-D-D (Gly-Asp-Asp) that is present in the RNA replicase of positive
      stranded RNA viruses. With the sequence data currently available, we carried out
      a phylogenetic analysis and obtained a genealogical relationship among members of
      the classical swine fever virus.

PMID- 9926398
TI  - DNA-antiviral vaccines: new developments and approaches--a review.
AB  - Current vaccines can be divided into "live," "recombinant" and "killed" vaccines.
      Live vaccines are traditionally composed of attenuated viruses or bacteria,
      selected for their reduced pathogenicity. Recombinant vaccines, driven by a viral
      or bacterial vector express foreign antigens, or only recombinant proteins
      injected as antigen. Killed vaccines consist of inactivated whole pathogens. But
      all these traditional vaccines have some disadvantages: Attenuated live vaccine
      are able to undergo mutation and as mutated viruses or bacteria can now provoke
      the diseases against which the vaccine should protect the organism. A further
      disadvantage of live vaccines is the possibility of shedding which is a real
      problem especially in veterinary medicine. Clearly, there is a need for better
      vaccines to protect against diseases without the disadvantages associated with
      vaccines presently in use. Modern vaccines might be characterized as safe, no
      risk of reversion to pathogenicity, and they should be stable without the
      necessity of a "cold chain." Production should be simple, standardized and
      inexpensive. Vaccine development has now been improved by the ability to use
      direct inoculations of plasmid DNA encoding viral or bacterial proteins. One of
      the major benefits of DNA-vaccines, variously termed "DNA-, genetic- or nucleic
      acid-immunization," is the endogenous synthesis of the encoded protein. Therefore
      DNA vaccines mimic natural infection and provoke both strong humoral and cellular
      immune response. This review summarizes new developments and approaches of DNA
      vaccination and explains the construction of expression plasmids as well as
      possible mechanisms of immune responses.

PMID- 9926399
TI  - A core promoter hairpin is essential for subgenomic RNA synthesis in alfalfa
      mosaic alfamovirus and is conserved in other Bromoviridae.
AB  - The nucleotide sequence immediately in front of the initiation site for
      subgenomic RNA 4 synthesis on RNA 3 minus strand, which has been proved to
      function as a core promoter, was inspected for secondary structure in 26 species
      of the plant virus family Bromoviridae. In 23 cases a stable hairpin could be
      predicted at a distance of 3 to 8 nucleotides from the initiation site of RNA 4.
      This hairpin contained several conserved nucleotides that are essential for core
      promoter activity in brome mosaic virus (R.W. Siegel, S. Adkins and C.C. Kao,
      Proc. Natl. Acad. Sci. USA 94, 11238-11243, 1997). Phylogenetic evidence and
      evidence from the effect of artificial mutations reported in the literature
      (E.A.G. van der Vossen, T. Notenboom and J.F. Bol, Virology 212, 663-672, 1995)
      indicate that the stem-loop structure is essential for promoter activity in
      alfalfa mosaic virus and probably in other Bromoviridae. Stability of the hairpin
      is most pronounced in the genera Alfamovirus and Ilarvirus which display genome
      activation by coat protein. The hypothesis is put forward that with these viruses
      the coat protein is needed for the viral RNA polymerase to interact with the core
      promoter hairpin leading to access for the enzyme to the initiation site of RNA
      4.

PMID- 9926401
TI  - Genetic analysis of the central untranslated genome region and the proximal
      coding part of the F gene of wild-type and vaccine canine distemper
      morbilliviruses.
AB  - Located between the open reading frames encoding the matrix (M) and the fusion
      (F) protein the morbillivirus genome contains an unusually large non-coding
      intercistronic region (M-F UTR) of up to 5.6% of the full length genome. Any
      function(s) of this region have largely remained obscure. Here, we analyze the M
      F UTR and the proximal coding part of the downstream F gene of several recent
      canine distemper morbillivirus (CDV) wild-type (wt) isolates and vaccine strains.
      While the F gene coding part appeared to be highly conserved (about 93%
      homology), a considerable degree of strain-specific variation of up to 21.4% was
      evident when comparing the M-F UTR. Phylogenetic analysis revealed a co
      circulation of several contemporary CDV genotypes within a close geographic range
      (central Europe). A remarkably distinct CDV wt lineage, so far detected only in
      mustelids, is displayed. A rather non-scattered pattern of mutations within the M
      F UTR suggested superimposition of RNA sequence and/or secondary structure
      constraints. Extensive folding in the long (460 nt) and moderately GC-rich 5'-UTR
      of the F mRNA was evident, particularly around the putative F protein translation
      initiation codon (AUG461 of the Onderstepoort vaccine strain). The region
      immediately preceding the putative F initiation site also harbored the only
      mutation unique to both vaccine strains within the F-5'UTR (position 455: Awt vs.
      Cvac). The putative F protein start codon, AUG461, was found to be mutated to AUA
      or GUA in all wt isolates analyzed and in another vaccine strain (Rockborn).
      Possible consequences for F protein translation initiation in wt CDV are
      discussed.

PMID- 9926400
TI  - Identification of a thymidylate synthase gene within the genome of Chilo
      iridescent virus.
AB  - The thymidylate synthase (TS, EC 2.1.1.45) is essential for the de novo synthesis
      of dTMP in pro- and eucaryotic organisms. Consequently it plays a major role in
      the replication of the DNA genome of a cell or a DNA virus. The gene encoding the
      TS of Chilo iridescent virus (CIV) was identified by nucleotide sequence analysis
      of the viral genome and was mapped within the EcoRI CIV DNA fragments G and R.
      Computer assisted analysis of the DNA nucleotide sequence between the genome
      coordinates 0.482 and 0.489 revealed an open reading frame (ORF) of 885
      nucleotides. This ORF was found to encode a polypeptide of 295 amino acid
      residues (33.9 kDa) that showed significant homologies to known TS of different
      species including mammals, plants, fungi, protozoa, bacteria, and DNA viruses.
      The highest amino acid homologies were found between the CIV-TS and the TS of
      herpesvirus ateles (54.0%), Saccharomyces cerevisiae (51.8%), herpesvirus saimiri
      (51.0%), rhesus monkey rhadinovirus (50.7%), mouse (50.5%), rat (50.2%),
      varicella-zoster virus (50.2%), equine herpesvirus 2 (50.0%), and the human TS
      (48.4%). The CIV-TS contains six amino acid domains that are highly conserved in
      the TS of other species. Within these domains the major amino acid residues are
      present for which a functional role has been reported. The CIV-TS was found to be
      more closely related to the TS of eucaryotes than to the TS of procaryotes
      indicating the phylogenetic origin of the CIV-TS gene. The identification of a TS
      gene in the genome of CIV is the first report of a viral TS that is not encoded
      by a herpesvirus or a bacteriophage.

PMID- 9926402
TI  - Cloning and sequence analysis of banana streak virus DNA.
AB  - Banana streak virus (BSV), a member of the Badnavirus group of plant viruses,
      causes severe problems in banana cultivation, reducing fruit yield and
      restricting plant breeding and the movement of germplasm. Current detection
      methods are relatively insensitive. In order to develop a PCR-based diagnostic
      method that is both reliable and sensitive, the genome of a Nigerian isolate of
      BSV has been sequenced and shown to comprise 7389 bp and to be organized in a
      manner characteristic of badnaviruses. Comparison of this sequence with those of
      other badnaviruses showed that BSV is a distinct virus. PCR with primers based on
      sequence data indicated that BSV sequences are present in the banana genome.

PMID- 9926403
TI  - Phylogenetic evidence for the improved RNA higher-order structure in internal
      ribosome entry sequences of HCV and pestiviruses.
AB  - The strong requirement for a small segment of the 5'-proximal coding sequence of
      hepatitis C virus (HCV) is one of the most remarkable features in the internal
      initiation of HCV mRNA translation. Phylogenetic analysis and RNA folding
      indicate a common RNA structure of the 5' untranslated region (UTR) of HCV and
      the animal pestiviruses, including HCV types 1-11, bovine viral diarrhea (BVDV),
      border disease virus (BDV) and hog cholera (HoCV). Although the common RNA
      structure shares similar features to that proposed for the internal ribosome
      entry sequence (IRES) of picornavirus, phylogenetic evidence suggests four new
      tertiary interactions between conserved terminal hairpin loops and between the
      terminal hairpin loop of F2b and the short coding sequence for HCV and
      pestiviruses. We suggest that the higher-order structures of IRES cis-acting
      elements for HCV and animal pestivirus are composed of stem-loop structures B-C,
      domains E-H, stem-loop structure J and four additional tertiary interactions. The
      common structure of IRES elements for these viruses forms a compact structure by
      these tertiary interactions and stem stacking. The active structural core is
      centered in the junction domain of E-H that is also conserved in all members of
      picornaviruses. Our model suggests that the requirement for a small segment of
      the 5' coding sequence is to form the distinct tertiary structure that
      facilitates the cis-acting function of the HCV IRES in the internal initiation of
      the translational control.

PMID- 9926404
TI  - Peptide and protein identification by matrix-assisted laser desorption ionization
      (MALDI) and MALDI-post-source decay time-of-flight mass spectrometry.
AB  - The potential of matrix-assisted laser desorption ionization (MALDI) and MALDI
      post-source decay (PSD) time-of-flight mass spectrometry for the characterization
      of peptides and proteins is discussed. Recent instrumental developments provide
      for levels of sensitivity and accuracy that make these techniques major
      analytical tools for proteome analysis. New software developments employing
      protein database searches have greatly enhanced the fields of application of
      MALDI-PSD. Peptides and proteins can be easily identified even if only a partial
      sequence information is determined. Derivatization procedures have been optimized
      for MALDI-PSD to increase the structural information and to obtain a complete
      peptide sequence even in critical cases. They are fast, simple and can be
      performed on target. MALDI-PSD is also a very powerful tool to characterize or
      elucidate post-translational or chemically induced modifications. In association
      with database searches, proteins issued from electrophoretic gels can be
      identified after specific enzymatic cleavages and peptide mapping.

PMID- 9926406
TI  - Determination of the dissociation kinetics of a transient intermediate.
AB  - Tandem mass spectrometry provides information on the dissociation pathways of gas
      phase ions by providing a link between product ions and parent ions. However,
      there exists a distinct possibility that a parent ion does not dissociate
      directly to the observed product ion, but that the reaction proceeds through
      unobserved reaction intermediates. This work describes the discovery and kinetic
      analysis of an unobserved reaction intermediate with a quadrupole ion trap. [a4 -
      NH3] ions formed from [YG beta FL + H] ions dissociate to [(F*YG - NH3) - CO]
      ions. It is expected, however, from previous results, that [F*YG - NH3] ions
      should form prior to [(F*YG - NH3) - CO] ions. Double-resonance experiments are
      used to demonstrate the existence of intermediate [F*YG - NH3] ions. Various
      kinetic analyses are then performed using traditional collision-induced
      dissociation kinetics and double-resonance experiments. The phenomenological
      rates of formation and decay of peptide rearrangement ion dissociation products
      are determined by curve fitting decay and formation data generated with the
      kinetics experiments. The data generated predict an observable level of the
      intermediate in a time frame accessible but previously not monitored. By
      examining early product-ion formation, the intermediate ions, [F*YG - NH3]+, are
      observed.

PMID- 9926405
TI  - Direct monitoring of protein-chemical reactions utilising nanoelectrospray mass
      spectrometry.
AB  - The feasibility of nanoelectrospray mass spectrometry (nanoESI) for the direct
      analysis of protein chemical reactions and structural changes of proteins has
      been evaluated. Taking advantage of the long spraying time and the capability of
      nanoESI for employing a wide range of solvent conditions such as buffers and
      detergents, applications of monitoring reaction pathways, and dynamics have been
      carried out with several peptides and proteins. The time course of proteolytic
      digestions with trypsin and pepsin was investigated for several model
      polypeptides, and nanoESI showed to provide an efficient tool for optimising
      digestion conditions for the mass spectrometric peptide mapping analysis.
      Examples of specific protein chemical modification reactions at arginine and
      tyrosine residues illustrate the feasibility of nanoESI to monitoring reaction
      yields and modification sites for more than 180 min. Furthermore, changes of the
      pattern of protonated molecules caused by temperature effects and by protein
      unfolding due to disulfide bond reduction have been studied with the model
      proteins cytochrome c and hen eggwhite lysozyme. The results indicate that
      nanoESI is an efficient technique for the direct, molecular characterisation of
      protein-chemical reactions in solution.

PMID- 9926408
TI  - Time-resolved measurements with single droplet introduction to investigate space
      charge effects in plasma mass spectrometry.
AB  - An investigation of the space-charge induced effects of high concentrations of
      Pb+ matrix ions on Li+ analyte ions in inductively coupled plasma mass
      spectrometry (ICP-MS) is presented using a vertically oriented mass spectrometer
      with single droplet introduction. Greater reproducibility and stability in
      droplet-to-droplet sample introduction using the monodisperse microparticulate
      injector (MDMI) was achieved with the vertical orientation. Typical variation
      (%RSD) in the droplet-to-droplet arrival times, and mass spectrometry peak
      analytical areas are better than 5%. With this precision, a more quantitative
      description of the space-charge effect on a single cloud of ions is obtained.
      Both radial and axial space-charge effects were found to occur in the ion beam.
      Radial effects result in a loss in intensity because of poor transmission or
      collisions at surfaces within the mass spectrometer. Axial effects modify the
      kinetic energy distribution of background ion beam components (e.g., 16O+ and
      40Ar+) and sampled ion cloud constituents (e.g., 7Li+). However, axial effects do
      not appear to generate significant broadening of sampled ion clouds within the
      mass spectrometer. At the point of charge separation and high ion-beam charge
      density, the ion cloud maxima for Li and Pb are not coincident. This is because
      of mass dependent diffusion in the ICP as the ion clouds approach the sampling
      orifice. Space-charge induced ion loss occurs predominantly at a localized region
      after the Li+ sampled cloud peak maximum. When the Pb concentration in the sample
      is sufficiently high the 7Li+ sampled signal has a bimodal peak shape. The
      existence of the dip and its relative location in the bimodal 7Li+ sampled signal
      suggests that space-charge effects are localized to the region of high charge
      density occurring just after charge separation.

PMID- 9926407
TI  - Flow injection with chemical reaction interface-isotope ratio mass spectrometry:
      an alternative to off-line combustion for detecting low levels of enriched 13C in
      mass balance studies.
AB  - We have evaluated the potential of flow injection chemical reaction interface
      isotope-ratio mass spectrometry to replace radioactive labeling techniques in
      material balance studies. A sample is flow injected and transmitted through a
      desolvation system followed by combustion to form 13CO2 with a microwave-powered
      chemical reaction interface. We can detect trace amounts of a 13C-labeled drug
      (3'-azido-3'-deoxythymidine, AZT) in urine or feces. Our ability to quantify less
      than 100 ng/mL of excess 13C (approximately 1 microgram/mL of 13C-labeled AZT)
      from a sample equivalent to 10 microL of urine is superior to previous detection
      limits for 13C in urine that use off-line combustion methods. Parallel studies
      using 14C-labeled AZT showed that our stable isotope method provides comparable
      percent excretion data for urine and feces. These results support previous
      findings that mass balance studies could be carried out with isotope-ratio mass
      spectrometer, here using doses as low as 1-2 mg/kg.

PMID- 9926409
TI  - Identification of in vitro metabolites of Indinavir by "intelligent automated LC
      MS/MS" (INTAMS) utilizing triple quadrupole tandem mass spectrometry.
AB  - In an effort to improve the efficiency of the TSQ 7000 LC-MS/MS system for
      identification of drug metabolites in biological matrices in support of drug
      discovery programs, a combination of instrument control language procedures for
      the Finnigan MAT TSQ 7000 mass spectrometer, referred to as INTAMS, were
      composed. INTAMS was designed to conduct unattended, automatic liquid
      chromatography/mass spectrometry (LC-MS) and LC-MS/MS analyses of drugs and
      metabolites in commonly encountered in vitro biological matrices. A novel peak
      detection algorithm was developed to automatically detect and record the
      pseudomolecular ions and retention times of chromatographic components, even if
      not fully resolved. This algorithm was used in combination with an automated
      technique for predicting the molecular weights of metabolites based on
      incremental changes of the molecular weight of the parent drug resulting from
      well-known biotransformation processes. When applied to a sample of an incubation
      mixture of the HIV protease inhibitor Indinavir with a rat liver S9 preparation,
      the results obtained by the automatic metabolite detection procedures for LC-MS
      and LC-MS/MS analyses in real time were the same as those which were determined
      manually, by a knowledgeable operator.

PMID- 9926410
TI  - Separation and detection of the alpha- and beta-chains of hemoglobin of a single
      intact red blood cells using capillary electrophoresis/electrospray ionization
      time-of-flight mass spectrometry.
AB  - A single intact red blood cell (erythrocyte) was injected into a capillary
      electrophoresis column, and following in-capillary lysing the alpha- and beta
      chains of the hemoglobin (approximately 450 amol) were separated and detected
      using capillary electrophoresis/electrospray ionization time-of-flight mass
      spectrometry. The mass specta of the electropherogram peaks of the alpha and beta
      chains showed identifiable peaks corresponding to multiply protonated and
      sodiated alpha- and beta-chains of hemoglobin.

PMID- 9926411
TI  - Homologues of the Cf-9 disease resistance gene (Hcr9s) are present at multiple
      loci on the short arm of tomato chromosome 1.
AB  - The tomato Cf-4 and Cf-9 genes map at a genetically complex locus on the short
      arm of chromosome 1 and confer resistance against Cladosporium fulvum through
      recognition of different pathogen-encoded avirulence determinants. Cf-4 and Cf-9
      are members of a large gene family (Hcr9s, Homologues of Cladosporium fulvum
      resistance gene Cf-9), some of which encode additional distinct recognition
      specificities. A genetic analysis of the majority of Hcr9s suggests that their
      distribution is spatially restricted to the short arm of chromosome 1. Two loci
      of clustered Hcr9 genes have been analyzed physically that mapped distal
      (Northern Lights) and proximal (Southern Cross) to the Cf-4/9 locus (Milky Way).
      Sequence homologies between intergenic regions at Southern Cross and Milky Way
      indicate local Hcr9 duplication preceded cluster multiplication. The
      multiplication of clusters involved DNA flanking Hcr9 sequences as indicated by
      conserved lipoxygenase sequences at Southern Cross and Milky Way. The similar
      spatial distribution of Hcr9 clusters in different Lycopersicon spp. suggests
      Hcr9 cluster multiplication preceded speciation.

PMID- 9926412
TI  - Mitotic stability of infection-induced resistance to plum pox potyvirus
      associated with transgene silencing and DNA methylation.
AB  - Plum pox potyvirus (PPV) infection of transgenic Nicotiana benthamiana plants
      that expressed the PPV NIb RNA replicase carrying a Gly to Val mutation at the
      GDD motif (NIbV lines) induced a phenotype of virus resistance and transgene
      silencing, which was not transmissible to the progeny after self-fertilization
      (H. S. Guo and J. A. Garcia, Mol. Plant-Microbe Interact. 10:160-170, 1997).
      Here, we demonstrate that the induced resistance of NIbV plants is mitotically
      stable after plant propagation by grafting and by in vitro regeneration. Virus
      replication or residual virus RNA seem not to be required to maintain transgene
      silencing and virus resistance. Analysis by PCR (polymerase chain reaction)
      amplification after treatment with methylation-sensitive restriction nucleases
      indicates that DNA methylation is associated with establishment and maintenance
      of transgene silencing and virus resistance. Restoration of transgene activity
      and susceptibility to PPV in sexual progeny correlated with resetting of
      transgene DNA methylation. On the basis of these and other published results, we
      present a general model for post-transcriptional gene silencing in which RNA
      signals, generated either by a silenced nuclear gene or by virus replication,
      both activate a specific cytoplasmic RNA degradation pathway and induce changes
      (in particular, DNA methylation) in homologous nuclear genes that switch them
      from an active to a silenced status.

PMID- 9926413
TI  - Virus particles of cucumber green mottle mosaic tobamovirus move systemically in
      the phloem of infected cucumber plants.
AB  - Systemic movement through the phloem of infected host plants is a key process in
      the life cycle of plant viruses, knowledge of which is scant. A main point to be
      elucidated is the structural form in which virus infection moves within the
      phloem. Indirect evidence suggests that virions might be the viral structure that
      moves in the phloem, but data from direct analysis in phloem sap have not been
      reported. We have done such analysis in the system cucumber (from which phloem
      exudate can be collected)/cucumber green mottle mosaic tobamovirus (CGMMV). CGMMV
      has structurally well-characterized particles. Both CGMMV coat protein and RNA
      were found in phloem exudate from infected cucumbers. Analysis of the
      accessibility of CGMMV RNA in phloem exudate to RNase A indicates that it is
      protected within a ribonucleoprotein structure. The accessibility to RNase A of
      the RNA in these structures was as in virus particles. Centrifugation analyses
      showed that the ribonucleoprotein structures in the phloem exudate have the same
      mass and isopycnic density as virions. Virus particles indistinguishable from
      purified virions were detected by electron microscopy in phloem exudate. No
      evidence of free RNA or other CGMMV-related structure was found in phloem exudate
      of infected plants. These results indicate that CGMMV movement in the phloem
      occurs mainly, if not exclusively, in the form of virus particles.

PMID- 9926414
TI  - Iron regulation and pathogenicity in Erwinia chrysanthemi 3937: role of the Fur
      repressor protein.
AB  - Low iron availability is a triggering signal for coordinated expression of the
      genes encoding pectate lyases PelB, PelC, PelD, and PelE, and chrysobactin iron
      transport functions, which are two main determinants of phytopathogenicity of the
      Erwinia chrysanthemi strain 3937. The possible implication of the ferric uptake
      regulation (Fur) protein in this process was investigated. The E. chrysanthemi
      fur gene was cloned by functional complementation of an Escherichia coli fur
      mutant and sequenced. The 444-bp open reading frame identified was found to code
      for a protein highly similar to the E. coli Fur regulator. An E. chrysanthemi fur
      null mutant was constructed by reverse genetics. This mutant showed altered
      growth capacity and reduced pathogenicity on African violets. In a fur
      background, transcriptional lacZ fusions to genes belonging to the E.
      chrysanthemi high affinity iron transport systems were constitutively expressed.
      Transcription of the pelA, pelD, and pelE genes was analyzed, using fusions to
      the uidA reporter gene. Iron availability and a fur mutation did not influence
      the expression of pelA. In the presence of iron, pelD and pelE transcription
      levels were higher in the fur mutant than in the parental strain. Furthermore,
      iron deficiency stimulated the expression of both fusions in the fur mutant.
      These findings indicate that, in E. chrysanthemi 3937, (i) Fur negatively
      controls iron transport and genes encoding PelD and PelE, and (ii) additional
      factor(s) mediate iron regulation of the pel genes.

PMID- 9926415
TI  - Restoration of wild-type virus by double recombination of tombusvirus mutants
      with a host transgene.
AB  - Nicotiana benthamiana plants transformed with the coat protein gene of tomato
      bushy stunt virus (TBSV) failed to elicit effective virus resistance when
      inoculated with wildtype virus. Subsequently, R1 and R2 progeny from 13
      transgenic lines were inoculated with a TBSV mutant containing a defective coat
      protein gene. Mild symptoms typical of those elicited in nontransformed plants
      infected with the TBSV mutant initially appeared. However, within 2 to 4 weeks,
      up to 20% of the transgenic plants sporadically began to develop the lethal
      syndrome characteristic of wild-type virus infections. RNA hybridization and
      immunoblot analyses of these plants and nontransformed N. benthamiana inoculated
      with virus from the transgenic lines indicated that wild-type virus had been
      regenerated by a double recombination event between the defective virus and the
      coat protein transgene. Similar results were obtained with a TBSV deletion mutant
      containing a nucleotide sequence marker, and with a chimeric cucumber necrosis
      virus (CNV) containing the defective TBSV coat protein gene. In both cases,
      purified virions contained wild-type TBSV RNA or CNV chimeric RNA derived by
      recombination with the transgenic coat protein mRNA. These results thus
      demonstrate that recombinant tombus-viruses can arise frequently from viral genes
      expressed in transgenic plants.

PMID- 9926416
TI  - Immunochemical characterization of somatic and metabolic antigens of 4 species of
      Aphanoascus: preliminary results.
AB  - Aphanoascus spp. are keratinophylic fungi occasionally described as etiological
      agents of tinea-like dermatomycoses. The goal of this work was to
      immunochemically characterize somatic and metabolic soluble antigens prepared
      from 4 species of Aphanoascus. Electrophoresis in SDS-PAGE gel and immunoblotting
      with sera from rabbits experimentally immunized with both somatic and metabolic
      antigens have shown a similar pattern among the species analyzed. However, some
      differences were noted between the species of Aphanoascus. These results suggest
      the existence of species-specific antigens.

PMID- 9926417
TI  - Evolutionary distances and identification of Candida species in clinical isolates
      by randomly amplified polymorphic DNA (RAPD).
AB  - Fast and reliable identification of different species of the genus Candida is
      important to define adequate therapeutic decisions, because the different species
      have highly variable susceptibilities to antifungal drugs; azoles and
      amphothericin B. Accurate statistical records on case history and epidemiological
      studies also depend on effective identification. To address this problem we
      established a RAPD method that enabled direct identification of five very common
      species of Candida. Initially, reference band patterns were established for C.
      albicans, C. tropicalis, C. parapsilosis, C. glabrata and C. krusei. One of the
      primers, M2, showed remarkably conserved intra-specific patterns of approximately
      10 bands each, ranging in size from 2.0 to 0.1 kb. These patterns were
      significantly different and species-specific. Few bands were conserved between
      different species of Candida, which was assumed to be consistent with their
      phylogenetic relatedness. In addition, band patterns were constant and
      reproducible and DNA isolated from single colonies yielded sufficient DNA for
      identification. The reference band patterns were then used, in blind experiments,
      to identify species of Candida in 50 randomly chosen samples, including clinical
      isolates and ATCC strains. RAPD results were 100% consistent with results
      obtained by conventional diagnostic methods and were achieved in one day instead
      of several days taken by conventional methods. Because ideal identification
      methods should be consistent with phylogeny and taxonomy we tested whether RAPD
      could be used to calculate genetic distances. Comparison of RAPD phylogenetic
      trees with 18S rRNA trees showed significant differences in tree topologies which
      indicated that RAPD data could not accurately measure the relative distances
      between different species. Also, computer simulations of RAPD random patterns
      were used to test whether the observed degree of RAPD band pattern similarities
      could occur at random. These simulations suggested that the level of inter
      specific band pattern similarities observed in our data could be obtained at
      random, while intraspecific pattern similarities could not. RAPD would be helpful
      to discriminate between isolates but not to quantitate the differences. We
      suggest that the inaccurate estimate of genetic distances from RAPD is a general
      limitation of the technique and not a specific problem of our identification
      method. Because of the repetitive character of the target sequences, genetic
      distances calculated from RAPD could be affected by paralogy, namely,
      recombination and duplication events not parallel with speciation events.

PMID- 9926418
TI  - Cloning and sequence analysis of Histoplasma capsulatum glucosamine-6-phosphate
      synthase gene fragment.
AB  - The 3' part of the glucosamine-6-phosphate synthase gene from Histoplasma
      capsulatum was PCR amplified using degenerate primers designed from the known
      glucosamine-6-phosphate synthase gene sequences, cloned and sequenced. The
      computer analysis of the 676 bp sequence revealed the presence of two introns.
      The identities of the deduced amino acid sequence to the corresponding
      Saccharomyces cerevisiae and Candida albicans fragment are 65 and 63.8%,
      respectively.

PMID- 9926419
TI  - Comparison of phospholipase production in Cryptococcus neoformans isolates from
      AIDS patients and bird droppings.
AB  - Secreted phospholipase has been recently proposed as a virulence determinant in
      Cryptococcus neoformans as well as Candida albicans. This issue of cryptococcal
      phospholipase requires screening of phospholipase production in a larger number
      of isolates from clinical and environmental sources. In this study we examined
      phospholipase production in a total of 67 C. neoformans isolates from AIDS
      patients and bird droppings by using the egg-yolk plate method. Phenoloxidase
      activity, capsule size and growth at 37 degrees C were also measured in these
      strains in order to observe a possible relationship between phospholipase
      production of different C. neoformans strains and its virulence. Four of the 21
      AIDS strains at 28 degrees C and 1 at 37 degrees C did not produce phospholipase,
      respectively. In contrast, 38 and 34 of the 46 bird dropping strains were
      negative for phospholipase production at 28, and 37 degrees C, respectively.
      Statistical analysis revealed a significant difference in phospholipase
      production, capsule size and growth ability at 37 degrees C, but not
      phenoloxidase activity, between the AIDS and the bird dropping strains. The
      highly prevalent distribution of phospholipase activity in the AIDS strains
      suggests a role of the enzyme in invading the host.

PMID- 9926420
TI  - Preharvest mycobial population of Indian jujube fruits (Ziziphus mauritiana
      Lamk.) and their implications in postharvest pathogenesis.
AB  - A mycological survey was carried out on the fruit surface of Indian jujube during
      its growth period (before harvest). A total of 32 microfungi belonging to 20
      genera were isolated by surface washing technique. Artificial inoculations with
      the isolated myco-propagules were also performed in mature jujube fruits and most
      of them were able to cause rot of varying severity. However, Monodictys
      castaneae, Eupenicillium lapidosum, Paecilomyces fumosoroseus, Trichurus spiralis
      and Acremonium spp., although present on the fruit surface, were not able to
      cause rot, indicating lack of specific macerating enzymes necessary for
      postharvest pathogenesis.

PMID- 9926421
TI  - Soil fungi of some low-altitude desert cotton fields and ability of their
      extracts to inhibit Aspergillus flavus.
AB  - Soil is presumed to be a major source of inoculum for Aspergillus flavus which
      contaminates cottonseed and produces the potent carcinogen, aflatoxin. Little is
      known about the mycoflora of the low desert soils of cotton fields where
      aflatoxin is a chronic problem. In this study, soils from cotton fields in
      southwestern Arizona and south-eastern California were assayed for filamentous
      fungi. Forty-two taxa, predominantly in the genera Aspergillus, Penicillium and
      Fusarium, were isolated. To determine whether or not compounds produced by these
      fungi could be potential inhibitors of A. flavus, extracts of strains of each
      taxon were tested for their ability to inhibit growth of A. flavus. Twelve taxa
      produced compounds inhibitory to A. flavus, including several strains of Fusarium
      solani, Penicillium vinaceum and Aspergillus auricomus.

PMID- 9926422
TI  - Rare symptoms and conidial variation in Septoria lycopersici in Zambia.
AB  - Surveys during the rainy season of 1996 showed that Septoria lycopersici
      developed two different types of leaf spots on tomatoes grown in kitchen gardens
      at the University of Zambia Campus and in nearby gardens. The two types of spots
      could be easily distinguished on the basis of their external morphology. One
      type, designated as T1, began as dark brown spots of less than 1 mm diameter.
      Upon increase in size, the spots differentiated into a dark brown outer ring and
      a grey centre, reaching a maximum diameter of 5 mm. Spots of this type are common
      and have been described in reports on Septoria leaf spot disease. A second type
      of spot found in our survey was designated as T2. This Septoria spot was greyish
      brown with several concentric rings of shrunken leaf tissue. The type T2 spots
      were larger and did not differentiate into two parts as in T1. The T2 spot
      diameter was 4-12 mm. The conidia showed differences in curvature, and
      significantly length, between T1 and T2. The study has shown that S. lycopersici
      in Zambia is variable.

PMID- 9926423
TI  - Analysis of Fusarium toxins in maize and wheat using thin layer chromatography.
AB  - Thin layer chromatography (TLC) methods for identifying and quantifying
      deoxynivalenol (DON), fumonisin B1 (FB1) and zearalenone in grain samples were
      compared to immunoassay (ELISA) and high performance liquid chromatography (HPLC)
      methods to determine the reliability of the less expensive TLC. There was a very
      good agreement between levels of DON measured by TLC and competitive-direct
      ELISA, and between levels of fumonisin B1 measured by TLC and HPLC, over a wide
      range of concentrations. Correlation coefficients (Pearson's) were 0.978, 0.914
      and 0.953 for DON in maize, DON in wheat and FB1 in maize respectively. A lower
      correlation coefficient (r = 0.672) was obtained when zearalenone was quantified
      by TLC and HPLC. Possible reasons for this are discussed. A cost comparison of
      the various methods revealed that TLC was the least expensive for sample
      analysis. It is recommended that researchers choose which analytical method to
      use based upon individual considerations of cost and precision.

PMID- 9926424
TI  - The influence of fungi on the long-term behaviour of radiocaesium in Norwegian
      sheep.
AB  - Results from 11 years of live monitoring of sheep from a grazing area in Norway
      formed the basis for a study of the importance of ingested fungal fruit bodies in
      determining radiocaesium activity concentrations in sheep grazing freely on
      mountain pasture. The 137Cs activity concentration due to ingested vegetation
      decreased with an estimated effective ecological half-life of 7.0 +/- 2.6 years.
      The contribution from ingested fungal fruit bodies to radiocaesium activity
      concentrations in the sheep was up to 75-85% in the years when fruit bodies were
      most abundant. The study demonstrates that using a simple exponential function in
      assessments of long-term consequences of radiocaesium fallout for grazing sheep
      may be inappropriate.

PMID- 9926425
TI  - Lead exposure in the general population of the Metropolitan Area of Barcelona:
      blood levels and related factors.
AB  - A cross-sectional study was conducted on 254 individuals not occupationally
      exposed to lead to determine the degree of lead exposure in the general
      population of the Metropolitan Area of Barcelona. Blood lead levels (BPb) were
      analysed by atomic absorption spectrophotometry and zinc protoporphyrin (ZPP) by
      haemofluorimetry. Blood lead levels were analysed with respect to individuals'
      age, sex, area of residence, the season of the year the blood was drawn and ZPP.
      Mean blood lead in our series was 0.22 +/- 0.011 mumol/l (mean +/- S.E.); no
      significant differences were found with respect to area of residence, sex or
      season. A linear relationship was observed between BPb and individuals' age (BPb
      = 0.08 + 0.05 x age; r = 0.37). The prevalence of lead intoxication (BPb > 0.48
      mumol/l) was 7.1%. No linear relationship was observed between BPb and ZPP. ZPP
      determination does not appear to be a good screening method for lead intoxication
      since it presents low specificity and sensitivity values with an area below the
      ROC curve similar to the null value line (area below the curve = 0.5052, IC 95% =
      0.443-0.568). We conclude that lead exposure does not constitute a serious health
      problem in the area studied, since BPb levels found are far below the toxic limit
      and the prevalence of intoxication is similar to that reported in other studies
      conducted in other developed countries.

PMID- 9926426
TI  - Seasonal deposition of housedusts onto household surfaces.
AB  - Seasonal differences in the particle size fractions and mass loadings of
      household dust deposited on indoor surfaces were examined in four New Jersey
      homes. Housedust was collected during a 30-day period on non-electrostatic
      polyethylene sample plates on which a glass slide had been placed. In each home
      two samples were collected at a height of 1.5 m and two were collected at a
      height of 0.3 m above the floor. Dust samples were obtained from each home during
      a summer and winter collection period. Particle size measurement was completed
      using an adaptation of a Meridian ACAS 570 Interactive Laser Cytometer. Results
      indicated that the dust mass deposited on household surfaces during the summer
      was greater than during the winter. The arithmetic mean mass deposition rate for
      all houses was 0.37 +/- 0.13 microgram/cm2/day during the summer and 0.22 +/-
      0.13 microgram/cm2/day during the winter. The total number of particles
      deposited, however, was greater during the winter than during the summer. The
      increase in winter time particle number was caused by greater numbers of
      particles with an equivalent spherical diameter < 2.5 microns. The most probable
      source of these particles was winter time combustion emissions within the
      residences and the subsequent particle deposition on household surfaces. The
      greater mass loadings measured on the low sampling plates during the summer were
      associated with a greater number of particles with an equivalent spherical
      diameter > 5 microns. In the winter, however, the particle mass and number
      loadings were similar at both heights. These results suggested that ventilation
      of the house during the summer allowed resuspended particles to enter which led
      to the higher levels of settled dust. Measurement of contaminant levels in
      housedust for exposure estimation therefore, should account for the seasonal and
      height differences in dust mass, and collect representative fractions of
      housedust that are available for human contact. Furthermore, since over 99% of
      the particles on indoor surfaces were < 50 microns any indirect sampling
      technique for dermal exposure estimation should have collection efficiencies
      similar to the hand of particles < 50 microns.

PMID- 9926427
TI  - Cadmium content in human kidney and hair in the Gdansk region.
AB  - Concentrations of cadmium were determined in the renal cortex and hair of 67
      persons who died between 1996 and 1997 in the Gdansk region of Poland. The mean
      concentrations in the renal cortex and the hair were: 39.8 +/- 21.45 micrograms/g
      and 0.35 +/- 0.33 microgram/g, respectively. The mean age of the population
      studied was 47.6 +/- 15.8 years. The concentration of cadmium in the renal cortex
      was age-dependent. In the age groups: 18-30, 31-40, 41-50, 51-60 and 61-90 it
      amounted to: 19.1 +/- 11.0 micrograms/g, 43.3 +/- 21.6 micrograms/g, 47.9 +/-
      20.8 micrograms/g, 41.5 +/- 20.4 micrograms/g and 33.6 +/- 18.0 micrograms/g,
      respectively. No correlation between the cadmium contents in the renal cortex and
      hair has been established. Hair is not a good indicator of exposure to cadmium.

PMID- 9926428
TI  - Spatial and temporal variations of herbicide (triazines and phenylureas)
      concentrations in the catchment basin of the Marne river (France).
AB  - Triazine and phenylurea concentrations were investigated in four sub-basins of
      the Marne river (France) in 1992 and 1993. The peak concentrations of atrazine,
      simazine and isoproturon occurred between March and July. In the four basins, the
      peaks were in relation with the herbicide application periods and with the
      important rainfalls, except for the isoproturon. The peaks of terbutryne and
      ametryne came later in the year, due to their use for weed control on post
      emergent corn. For the phenylureas, the peak concentrations were observed in
      March-April next to the spraying period on winter cereals. The fast transfer of
      those herbicides was related to their high water solubility. In all the samples,
      the deethylatrazine (DEA) was detected 1 month after the atrazine due to its
      degradation within the soils which is of minor importance as compared to its
      transport by surface waters and also, to interactions between the silt sheet and
      the stream itself. The DAR evolution showed that the atrazine residence time
      depends both on the run-off in the first centimetres of the soil and on the
      treatment periods, particularly in the Grand Morin. The Marne river contamination
      level was similar to that of the Melarchez and of the Grand Morin. The minor
      pollution of the Orgeval was related to minor cultivated areas.

PMID- 9926429
TI  - Man, nutrition and mobility: a comparison of teeth and bone from the Medieval era
      and the present from Pb and Sr isotopes.
AB  - Naturally occurring isotopic systems, such as strontium (Sr) and lead (Pb), are
      very useful for characterizing different sources and to produce background
      information. Norwegian teeth from the Medieval era have 206Pb/204Pb ratios
      between 18.8 and 18.2, in comparison with present day ratios of between 18.0 and
      17.6 showing the impact of Pb from modern industrialization and from traffic. Sr
      analyses of Medieval teeth show that an individual living in a coastal town on
      the west coast of Norway can easily be distinguished from one in a rural area at
      that time. The Sr signature shows that Medieval people lived on local products
      while present people to a greater degree live on imported or domestic
      industrially processed food. Medieval and modern teeth from one site give similar
      Pb signatures and concentrations indicating no increase in pollution over time.
      However, the impact of industrial pollution can be seen from Pb analyses on
      contemporary teeth, so that the method can be used to monitor emission of heavy
      metals from local industry. Whilst the Pb and Sr natural isotopic systems
      individually provide valuable information, a combination of the two techniques is
      a very powerful tool in environmental and archaeological research.

PMID- 9926430
TI  - Lead leaching from pressure cookers.
AB  - Leachability of lead by tap water and tamarind solution from Indian pressure
      cookers while cooking with and without a safety valve is studied. Lead
      contamination of food by cookers is not very high when compared to the daily
      intake of lead from various food items consumed by the Indian community. However,
      looking at the very wide range of lead levels leached from various brands of
      pressure cookers, it certainly seems possible to keep the lead contamination to
      the minimum by proper choice of the materials used in the manufacture of these
      pressure cookers. The rubber gasket, which is a very important component of any
      pressure cooker, contains the maximum lead concentration; the safety valve is
      another important source leading to lead contamination of cooked food.

PMID- 9926431
TI  - Insensitivity of the routine dimethylglyoxime test for detecting release of
      nickel from earrings.
AB  - The Helsinki City Centre of the Environment tested two methods, dimethylglyoxime
      (DMG) and atomic absorption spectrometry (AAS), for detecting nickel release in
      piercing earrings. The DMG screening test was performed in two slightly different
      ways, with and without ethanol and heat prehandling. All 30 pairs of earrings
      tested, totalling 66 objects, were negative. However, according to our AAS test,
      25 of the 66 objects (38%) released > or = 0.05% of nickel, the mean amount being
      2.1% and the maximum 12%. When measured by AAS after artificial sweat treatment,
      11 objects released more than 0.5 microgram/cm2 per week of nickel, the mean
      amount being 3.4 micrograms/cm2 and the range < 0.1-84 micrograms/cm2. After this
      sweat treatment, nine of the objects (14%) were positive in DMG tests. These
      findings indicate that the DMG test is unreliable for detecting nickel release
      from jewelry. Quality control of consumer items should be performed by
      laboratories that have quantitative analysis methods for such investigations.

PMID- 9926432
TI  - Resistance to antibiotic and heavy metals of motile aeromonads from Chilean
      freshwater.
AB  - In this work the resistance of 172 motile Aeromonas isolates recovered from raw
      drinking water supplies (56), irrigation waters (60) and runoff waters receiving
      sewage (56), to some antibiotics and heavy metals was investigated by agar
      diffusion and agar dilution methods. A high proportion of isolates from all water
      sources showed resistance to carbenicillin, erythromycin, streptomycin,
      cephradine and cadmium, and susceptibility to chloramphenicol, kanamycin,
      gentamicin, tetracycline, nalidixic acid, trimethoprim-sulphametoxazole and
      chromium. No amikacin-resistant Aeromonas were recovered. No relationship was
      found between antimicrobial resistance and Aeromonas species, with the exception
      of cephradine, that exhibited a significantly higher activity against the A.
      sobria isolates than the other Aeromonas species (P < 0.05). Moderately polluted
      waters showed lower antibiotic multiresistance and metal susceptibility than
      unpolluted and highly polluted ones. Although significant differences (P < 0.05),
      between resistance frequencies to erythromycin, carbenicillin, streptomycin and
      cephradine were found among isolates from different sources, the antimicrobial
      resistance patterns of aeromonads could not be related to the level of faecal
      pollution. These results indicate that aeromonads resistant to antibiotics and
      heavy metals are easily recovered from water sources in Chile, posing a potential
      public health risk.

PMID- 9926433
TI  - Effects of mouth cleansing on the levels of exhaled nitrous oxide in young and
      older adults.
AB  - Nitrous oxide (N2O) is produced by denitrification, i.e. by microbial reduction
      of nitrate (NO3-). Our previous studies have established an analytical method for
      demonstrating the existence of N2O in exhaled air, and we showed that levels of
      N2O in exhaled air increase with age after puberty. However, the source of this
      change and its biological significance are still unclear. The purpose of this
      study was to examine whether the oral microorganisms are the main source of N2O.
      We measured exhaled N2O in 35 young adults (aged 19-29 years) and 34 older adults
      (aged 61-79 years) before and after mouth cleansing. N2O was measured using an
      infrared-photoacoustic analyzer equipped with an optical filter (UA0985, 2215 cm
      1). Participants were classified as producers and non-producers according to the
      levels of exhaled N2O relative to the level in the atmosphere. N2O production
      differed significantly between the young adult producers and the older adult
      producers. Mouth cleansing resulted in an immediate reduction in exhaled N2O in
      both groups. We only found seven (20.0%) producers in the young, and 32 (94.1%)
      producers in the older after mouth washing. The differences before and after
      mouth cleansing were significant in both groups (P < 0.01 in the young and P <
      0.05 in the older). The oral cavity is a major source of N2O. However, since
      approximately half-levels of N2O were still observed in exhaled air after mouth,
      cleansing, there may exist another N2O source in the human body.

PMID- 9926434
TI  - Mercury in the bivalve Anadara (Senilia) senilis from Ghana and Nigeria.
AB  - Samples of the bivalve Anadara (Senilia) senilis collected from a closed lagoon
      (Sakumo) and two open lagoons in Ghana (Benya and Ningo; n = 550), and the Bonny
      river estuary in Nigeria (n = 620), were analyzed for their total and organic
      mercury content. Total mercury concentration showed significant spatial
      differences, with median values of 0.1 microgram/g dry wt. in the closed lagoon,
      0.2 in the estuary and 0.3 in the open lagoons. Concentration tended to be higher
      during the dry season in the lagoons, but lower in the estuary. The median
      relative organic concentration varied between 20 and 60% methyl Hg, depending on
      location and season. Age effects were detected in the lagoons, total Hg
      concentration decreasing with length.

PMID- 9926435
TI  - Evaluation of enzyme-linked immunosorbent assay for the determination of
      polycyclic aromatic hydrocarbons in house dust and residential soil.
AB  - Two commercially available enzyme-linked immunosorbent assays (ELISA) for total
      polycyclic aromatic hydrocarbon (PAH) and carcinogenic PAH (C-PAH) were
      evaluated. The testing procedures were refined for application to screening PAH
      and C-PAH in house dust and soil samples for human exposure studies. The overall
      method precision expressed as percent relative standard deviation (%RSD) of
      triplicate real world dust and soil samples was within +/- 29% (12-29%) for PAH
      ELISA and +/- 21% (5.9-21%) for C-PAH ELISA. Spike recoveries from real world
      dust/soil samples were 114 +/- 30% for phenanthrene from PAH ELISA and 120 +/-
      8.2% for benzo[a]pyrene from C-PAH ELISA. The overall method accuracy for PAH and
      C-PAH assays cannot be assessed for multiple PAH components in dust/soil samples
      (which represent real-world samples), because of the assays' cross reactivities
      with other PAH components. Over 100 dust/soil samples from 13 North Carolina
      homes and 22 Arizona homes were analyzed by PAH and C-PAH assays, as well as by
      the conventional gas chromatography/mass spectrometry (GC/MS) method. Statistical
      analysis showed that dust/soil PAH data from ELISA and GC/MS methods are
      significantly different. In general PAH ELISA responses were higher than PAH
      GC/MS responses. The regression analysis showed that the linear relationship
      between ELISA and GC/MS measurements is not strong in the combined data. The
      relationship became stronger for the data from the same type of dust/soil
      samples. The screening performance of ELISA was evaluated based on the frequency
      distribution of ELISA and GC/MS data. The results indicated that the ELISA PAH
      and C-PAH assays cannot be used as a quantitative analytical tool for determining
      PAH in real-world dust/soil samples. However, the ELISA is an effective screening
      tool for ranking PAH concentrations in similar types of real world dust/soil
      samples.

PMID- 9926436
TI  - Indicators of human health in ecosystems: what do we measure?
AB  - Increasingly, scientists are being called upon to assist in the development of
      indicators for monitoring ecosystem health. For human health indicators, they may
      draw on environmental exposure, human morbidity/mortality or well-being and
      sustainability approaches. To improve the rigour of indicators, we propose six
      scientific criteria for indicator selection: (1) data availability, suitability
      and representativeness (of populations), (2) indicator validity (face, construct,
      predictive and convergent) and reliability; (3) indicator responsiveness to
      change; (4) indicator desegregation capability (across personal and community
      characteristics); (5) indicator comparability (across populations and
      jurisdictions); and (6) indicator representativeness (across important dimensions
      of concern). We comment on our current capacity to adhere to such criteria with
      examples of measures of environmental exposure, human health and sustainability.
      We recognize the considerable work still required on documenting environment
      human health relationships and on monitoring potential indicators in similar ways
      over time. Yet we argue that such work is essential in order for science to
      inform policy decisions which affect the health of ecosystems and human health.

PMID- 9926437
TI  - Delayed visual maturation and lead pollution.
AB  - Three children were born in the Broken Hill Australia lead mining community with
      delayed visual maturation of the optic nerve (blindness) within a period of 19
      months. Because of the association with the lead pollution, the delayed visual
      maturation was attributed to lead exposure of the fetus during pregnancy. Lead
      isotopic analyses of the shed deciduous teeth from the three children demonstrate
      that they were not exposed to increased levels of lead from a mining or any other
      source during pregnancy and the etiology of the delayed visual maturation must be
      sought elsewhere.

PMID- 9926438
TI  - Effect of preadsorbed background organic matter on granular activated carbon
      adsorption of atrazine.
AB  - This study examines the effect of preadsorbed background organic matter (measured
      as dissolved organic carbon, DOC) on the granular activated carbon (GAC)
      adsorption of atrazine. Thirty-four experiments were conducted in batch
      contactors using organic-free laboratory water (< 0.1 mg/l DOC) and pilot-column
      GAC, preloaded with DOC for 3-20 weeks (equivalent to 4.3-32 mg DOC/g GAC).
      Freundlich isotherms were determined for adsorption of atrazine at initial
      concentrations from 10 to 1000 micrograms/l. The isotherm data indicate that GAC
      capacities for atrazine are only moderately reduced by preadsorbed DOC. At an
      initial concentration of 1000 micrograms/l atrazine, the GAC capacity for
      atrazine decreases by -1.0 mg atz/mg preadsorbed DOC. At an initial concentration
      of 10 micrograms/l atrazine, the GAC capacity for atrazine decreases by only 
      0.40 mg atz/mg preadsorbed DOC. For the pilot-column GAC preloaded with a maximum
      of 32 mg DOC/g GAC, the decrease in capacity for atrazine averages -33 +/- 13%.

PMID- 9926439
TI  - The global problem of cardiovascular disease.
AB  - The greatest cause of death throughout the world today is noncommunicable
      disease. In Western societies, coronary artery disease is a principal cause of
      death. In developing countries, the incidence of coronary disease is rising as
      well. Heart disease often occurs in younger persons in developing societies,
      resulting in a disproportionately greater number of years of life lost. The
      reason for this change in global patterns of mortality is that deaths from
      infectious diseases are declining, resulting in greater life expectancy and
      changing lifestyles.

PMID- 9926440
TI  - Emerging approaches in the prevention of atherosclerotic cardiovascular diseases.
AB  - This presentation reviews data from epidemiologic and clinical trials on
      antioxidant vitamins, angiotensin-converting enzyme inhibitors, and homocysteine
      and their effect on atherosclerotic cardiovascular disease. Each of these areas
      seems promising, but the results of large, on-going studies must be determined
      before definitive conclusions can be made as to the effectiveness of these
      therapies.

PMID- 9926441
TI  - The renin-angiotensin system and vascular fibrinolytic balance.
AB  - Haemostasis depends on an intricate relation among plasma coagulation and
      fibrinolytic factors, blood cells, vessel walls, extracellular matrix, blood
      viscosity, and blood flow. Hormonal systems, such as the renin-angiotensin system
      (RAS) act as a protector against acute fluid volume loss by inducing both
      vasoconstriction to maintain blood pressure and the retention of salt and water
      to restore normal fluid volume. Studies have confirmed that this cascade of
      events is brought into action by the RAS in coordination and sequentially.
      Inappropriate activation of the RAS may occur, however, in patients with left
      ventricular dysfunction and heart failure. Angiotensin-converting enzyme
      inhibitors are indicated to counteract the vasoconstriction and salt and water
      retention associated with activation of the RAS.

PMID- 9926442
TI  - Towards 2001: will ACE inhibitors have a role in atherosclerosis treatment?
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been in clinical use for 20
      years, during which time their application has been extended from the treatment
      of hypertension and heart failure to left ventricular dysfunction after
      myocardial infarction. They are also being used today for the treatment of
      diabetic nephropathy. More recently, the rationale for an antiatherosclerotic
      effect of ACE inhibition has emerged, based on more detailed understanding of the
      renin-angiotensin-aldosterone system and the role of this system in
      atherogenesis, in addition to supportive experimental animal and preliminary
      clinical data. The possible clinical benefit of ACE inhibition in atherosclerosis
      is currently being assessed in several large-scale trials with both surrogate and
      clinical outcome measures in high-risk patients with clinically manifest
      atherosclerosis, principally coronary artery disease. The trials should further
      elucidate the mechanisms of benefit from ACE inhibition and further define their
      role in therapy of patients with coronary disease.

PMID- 9926443
TI  - Clinical implications for the Acute Infarction Ramipril Efficacy extension
      (AIREX) Study.
AB  - It is now clear that angiotensin-converting enzyme (ACE) inhibitor treatment
      after myocardial infarction (MI) reduces mortality and morbidity. However, the
      benefits of ACE inhibition are not homogeneous and are largely confined to high
      risk patients who have subjective or objective evidence of left ventricular (LV)
      dysfunction. How long treatment should continue is a vexed question, which also
      arises with other agents, for example beta-blocker use after MI. The AIREX study
      assessed the long-term magnitude and duration of the survival benefits observed
      with ramipril in patients after MI who have clinically defined heart failure. The
      mortality status of all 603 patients recruited from the UK centres involved in
      the AIRE study was verified at an extended 5-year follow-up (3 years after the
      AIRE study closed). Ramipril assignation was associated with a 36% relative and a
      11% absolute mortality risk reduction. These findings strongly support the view
      to select patients on the basis of impaired LV function and reinforce the
      previously reported conclusions of the "selective" ACE inhibition post-MI trials.
      Using this approach, the survival benefit is not only of large magnitude but also
      sustained over many years. These results also argue for life-long treatment with
      an ACE inhibitor, once a decision to treat an individual patient after MI has
      been made.

PMID- 9926444
TI  - Heart failure treatment: the state of Austrian clinical practice--the Cor survey.
      Cor Survey Study Group.
AB  - The aim of this observational study was to evaluate how patients with heart
      failure (HF) are treated in Austria and which variables may influence usage and
      dosage of angiotensin-converting enzyme (ACE) inhibitors. One hundred fifty-five
      hospital departments throughout Austria took part by responding to questionnaires
      on 4331 patients with a primary or secondary diagnosis of HF who were discharged
      during November 1996. A total of 1896 patients (44%) were taking an ACE inhibitor
      at admission, 868 (20%) patients were started on ACE inhibitor therapy in the
      hospital, and 64% were discharged while taking an ACE inhibitor. Triple therapy
      (ACE inhibitor, glycoside, and diuretic) was used in 34% of the patients.
      Conditions favoring ACE inhibitor therapy were hypertension (77%), diabetes (75%
      insulin-dependent, 70% non-insulin dependent), and age below 75 years (71%).
      Functional stage, gender, presence of chronic obstructive pulmonary disease or
      atrial fibrillation, and a history of stroke had little influence on the
      prescription of ACE inhibitors. They were used infrequently and, if so, in low
      doses in patients with a serum creatinine levels above 2.0 mg/dL, the aged, or
      those with dementia. Geographic location also affected medication use. More
      educational efforts and more scientific evidence on the issue of adequacy of
      different doses will be needed in order to take full advantage of the beneficial
      potential of ACE inhibitors in the therapy of patients with HF in the future.

PMID- 9926445
TI  - [Carcinoma of the hypopharynx and esophagus].

PMID- 9926446
TI  - [Classification of ethmoid malignancies].
AB  - The UICC and AJCC never classified ethmoid malignancies prior to the latest
      edition (1997). Most classifications in the literature refer to a single
      histological type (estensioneuroblastoma or carcinoma) while others basically
      consider the intracranial extension, without distinguishing between intra or
      extradural. Still others consider invasion of the orbit. There is as yet no
      classification which considers all the prognostic factors associated with the
      extension of this neoplasm. The authors reviewed 84 patients with ethmoid
      malignancy who had undergone anterior cranio-facial resection between 1987 and
      1994 and had been followed up for a minimum of 36 months. Of these patients, 43
      were recurrences of previous treatment while 42 had not previously been treated.
      The breakdown was as follows: 45 adenocarcinoma, 14 squamous cell carcinoma (more
      or less differentiated), 8 etesioneuroblastoma, 6 adenoidocistic carcinoma, 5
      melanoma and 6 rare forms. These cases were staged according to a new
      classification identifying the worst prognostic factors: invasion into the dura
      and, above all, intradural extension; invasion of the sphenoid sinus, orbit, and
      in particular the orbit apex, the frontal sinus, the maxillary sinus, the
      pterygoid, infratemporal fossa and the skin. Until 1994 we used this
      classification which is similar to the one proposed by the UICC in 1997. On the
      basis of this classification our case breakdown is as follows: T2 35, T3 24, T4
      25 (there were no cases of T1). Since a patient can live as much as 4-5 years
      with a recurrence but the recurrences all appeared within 2 years after surgery,
      we used a NED survival at 36 months as index of healing. The NED survival at 36
      months was: T2 54%, T3 41%, T4 8%. In patients which had not received prior
      treatment the NED survival was: T2 63%, T3 45%, T4 9%. The progressive worsening
      of prognosis from T2 to T4, particularly in patients which had not been
      pretreated, leads us to assume that the true prognostic factors for malignant
      ethmoid tumors have been identified.

PMID- 9926447
TI  - [Analysis of qualitative voice and speech quality judgments after total
      laryngectomy].
AB  - The present work analyzes subjective judgement of the voice and speech qualities
      of intelligibility, pleasantness and acceptability expressed for two groups of
      total laryngectomy patients. The first group was composed of ten patients who had
      undergone esophageal voice rehabilitation. The second had nine patients with
      tracheo-esophageal voice rehabilitation. A group of ten listeners was set up to
      evaluate the voice and language parameters. These were all persons who, because
      of their jobs (i.e. physicians, nurses, rehabilitation therapists, etc.), had
      nearly daily contacts with laryngectomized patients. The listeners had to
      evaluate the acoustic and qualitative features of the voices reproduced on
      magnetic tape and score them on a specially designed sheet. This study has
      revealed a significant difference in the voice and speech acceptability scores
      for the two different groups of patients. In fact, most of the listeners found
      the tracheo-esophageal voice more pleasant and more acceptable than the
      esophageal voice.

PMID- 9926448
TI  - [Labayle's supracricoid partial laryngectomy in the treatment of laryngeal
      cancer: personal experience and long term follow up].
AB  - The present study was carried out to assess the indications and to evaluate the
      functional and oncological results of the supracricoid laryngectomy with crico
      hyoid-pexy proposed by J. Labayle. This technique consists of a sub-total
      laryngectomy where the cricoid cartilage, the hyoid bone and at least one of the
      arytenoids are spared. These structures can then be reassembled into a "neo
      larynx", thus preserving respiration and phonation. The present paper deals with
      23 laryngeal carcinomas: 13 glottic (2 T1bN0, 6 T2N0, 1 T2N1, 1 T2N1, 3 T3N0) and
      10 supraglottic (4 T2N0, 3 T2N1, 3 T2N2). The follow-up shows a 5-year overall
      actuarial survival rate of 80.65%. The authors agree that when performed under
      very precise indications the crico-hyoid-pexy is a useful alternative to both
      radiotherapy and the extended-partial or total laryngectomy in the treatment of
      laryngeal carcinoma. It also appears useful in treating selected cases of post
      surgical or post-radiotherapy recurrences.

PMID- 9926449
TI  - [A computerized database for managing otorhinolaryngologic oncology patients].
AB  - In recent years the management and interdisciplinary treatment of oncological
      patients has become extremely complex due to the progress made in diagnosis and
      therapy. As a result, the knowledge required to treat patients can no longer be
      simply memorized or manually filed. Computer technology provides the ideal
      instrument for organizing, saving and analyzing data from head and neck tumor
      patients. The authors have prepared a computerized database to meet the following
      needs: ease of use, even for non computer savvy users; minimal ambiguity for data
      entry; use for both clinical and scientific purposes; possibility to create a
      network with similar database at other Centers; possibility to expand to include
      image management. The archive is based on a personal computer with an INTEL 80486
      microprocessor, 40 Mb RAM, DOS 6.0. and Windows 3.1. The software includes four
      main routines: a) formulation and management of tables where oncological data are
      gathered; b) entry and management of patient-related clinical data; c)
      statistical processing for epidemiological and oncological research and; d)
      management of basic computer services. In clinical practice the database allows
      the following: a) preparation of a monthly chart of check-ups, b) rapid tracking
      of patients lost to followup, c) printout of a summary of the clinical history of
      each patient at the time of check-up and rapid updating at the end of the
      examination, d) automatic production of forms such as discharge letters and
      reports to be shared with related services (i.e. medical oncology, radiotherapy).
      In addition, the database is a powerful, versatile research tool which can
      promptly provide all sorts of oncological data and can automatically prepare
      tables, diagrams, correlations, survival curves. The system was developed from
      1993 to 1995 and has been operative, with a few minor modifications and updates,
      since 1995. Today the database contains more than 1200 oncological cases and the
      system is used daily by medical and paramedical personnel alike. Approximately 15
      new cases are entered a month and 80 cases updated after follow-up.

PMID- 9926451
TI  - [Sudden hearing loss complicating general surgery: report of a case and review of
      the literature].
AB  - A case of sudden sensorineural hearing loss following abdominal surgery is
      reported. In addition, all cases of sudden hearing loss following general surgery
      found in the literature are re-examined. This analysis indicates that either this
      pathology is extremely rare (only 15 cases have been reported in the literature,
      plus the present case) or, more likely, that little attention is paid to the
      relationship between general surgery and sudden hearing loss. In the author's
      opinion a causal relationship between the two events is highly unlikely. He
      analyzes the possible pathogenic mechanisms and indicates that other cases should
      be promptly reported so that greater insight into this pathology can be obtained.

PMID- 9926450
TI  - [Therapeutic strategies for the treatment of parotid gland malignancies].
AB  - Parotid gland neoplasms include a quite heterogeneous group of histotypes with
      markedly different biological characteristics and evolution, thus requiring
      different forms of treatment. The present study evaluated the effects surgery and
      radiotherapy have on local disease control, survival rates and onset of
      locoregional recurrences. 126 malignant parotid tumors were examined (59 males,
      67 females; age range 11 to 88 years; mean age 62 years) with a minimum of 1 year
      follow-up. The most malignant tumors were those most frequently seen in this case
      study (68%). Surgery was performed in 81 subjects (83.5%). Conservative total
      parotidectomy was the procedure most frequently performed (60/81, 74%). The
      overall 5-year survival rate was around 54% while 47% were "disease-free"
      patients at 5 years. When the subjects were broken down into 2 groups according
      to the degree of malignancy (high or low), the survival curve for disease-free
      subjects showed some differences (respectively 52% and 42%). The choice of
      treatment for the primary T significantly affect survival. Radiotherapy alone
      proved much less satisfactory than surgery (p < 0.01). The 5-year survival rate
      following a combination of surgery and subsequent radiotherapy was 52%, while it
      was 47% for those treated by surgery alone. An examination of the type of surgery
      performed revealed a difference in survival between those treated with
      preservation of the VII cranial nerve (52% at 5 years) and the more radical
      surgery (43% at 5 years) although this difference was not statistically
      significant. The incidence of recurrence was 25.7% (25 cases out of 97), of which
      88% arose within the first 2 years. In conclusion, it has been seen that
      malignant parotid gland neoplasms are highly aggressive and the treatment of
      choice appears to be surgery plus radiotherapy whenever the clinical-biological
      features of the neoplasm warrant it. The surgical approach to the facial nerve
      should be as conservative as possible, reserving utmost radicality for the most
      advanced cases compromising the adjacent structures.

PMID- 9926452
TI  - [Laryngeal myoblastoma in childhood].
AB  - Laryngeal tumors originating in the nerves are extremely rare, particularly in
      infants. Indeed, this type of neoplasm normally arises in adult males. Only 10
      cases have been described in the 5 to 17 year age range. The present work reports
      a clinical case of granulous tumor of the larynx in an 11-year-old boy.
      Histologically this tumor showed cells which preserved their original structure
      and were in close relation with the nerve fibers, but not with the myocytes.
      Their metabolic activity was similar to that of the nerve cells. The neurogenic
      origin of the neoplastic granulous cells shows the presence of neuroectodermic
      cytoplasmic S-100 specific for cells derived from the neural crest. The boy
      manifested ingravescent dyspnea due to the presence of a myoblastoma in the right
      laryngeal ventricle. A thyrotomic approach was adopted because of the significant
      size of the neoplasm although it was possible to perform conservative surgery
      given that the lesion was benign. The authors underline the polymorphic histology
      of this neoplasm and the importance of the type of surgery which should both
      avoid widespread demolition since the neoplasm is benign and, at the same time,
      prevent recurrences.

PMID- 9926453
TI  - [Otoacoustic emissions originating from the cochlea].

PMID- 9926454
TI  - Reintroduction of bovine herpes virus type 1 into Danish cattle herds during the
      period 1991-1995: a review of the investigations in the infected herds.
AB  - In Denmark a programme for the systematic eradication of bovine herpes virus 1
      (BHV-1) was completed during the years 1984 to 1991, but outbreaks due to new
      introductions of BHV-1 were seen. Between January 1991 and May 1994, 22 herds
      became infected with BHV-1, all located closely to the German border. In 1995, 61
      herds were detected BHV-1 antibody positive, but they were situated in many
      different parts of Denmark. In order to find the source of infection owners of
      infected herds were interviewed, and restriction fragment pattern analysis (RFP
      analysis) was performed on virus isolates from the herds with clinical outbreaks.
      Isolates from clinical outbreaks up to 1995 were identified as a Cooper-like
      strain, while 2 of those in 1995 had characteristics of a "new" strain, which had
      never before been identified in Denmark or elsewhere in Europe. In the described
      situation different transmission routes for virus seemed possible. One being a
      sporadic introduction of virus due to accidental contact with infected cattle
      near the German border or maybe due to an airborne transmission of virus over
      longer distance. The other, presumably a result of import of an infected animal
      despite the national regulations. The latter, due to an extensive trade pattern,
      resulted in the introduction of infected cattle into 51 BHV-1 seronegative cattle
      herds.

PMID- 9926455
TI  - In situ hybridization for the detection of infectious laryngotracheitis virus in
      sections of trachea from experimentally infected chickens.
AB  - An in situ hybridization procedure for the detection of infectious
      laryngotracheitis virus (ILTV) in experimentally infected chickens is described.
      Formalin-fixed, paraffin-embedded sections of trachea, taken from chickens on
      days 3-10 post-inoculation (p.i.) with ILTV were hybridized with a mixture of 2
      biotinylated, polymerase chain reaction-generated DNA fragments. The fragments
      correspond to sequences of the ILTV glycoprotein C and thymidine Kinase genes. In
      situ hybridization was seen in 7 out of 7 chickens examined on day 3 p.i., 2 out
      of 2 examined on day 4 p.i. and 3 out of 3 examined on day 5 p.i. No
      hybridization was observed in 3 out of 3 chickens examined on day 10 p.i. ILTV
      nucleic acid was detected in nuclei of degenerated tracheal epithelial cells and
      in intranuclear inclusion bodies of syncytia.

PMID- 9926456
TI  - Bacteriological and histological investigation of the postpartum bovine uterus in
      two Estonian dairy herds.
AB  - Postpartum uterine infections, endometrial histology and resumption of ovarian
      activity in cows were studied in 2 Estonian dairy herds with different herd
      sizes, milk yields and management systems. Ten cows at Farm A and 5 cows at Farm
      B were studied in the experiment. All cows in the study had normal calving
      performance. Endometrial biopsies for bacteriological and histological
      examinations were collected once a week starting on the second week postpartum
      and continuing for 7 weeks postpartum. Milk progesterone samples were collected
      twice a week during the whole study period. In both herds, the uterine flora
      contained mainly facultative anaerobic bacteria (Streptococcus spp., E. coli,
      Staphylococcus spp., Proteus vulgaris). Among obligate anaerobic bacteria only
      Bacteroides spp. were found. After 7 weeks of collection at farm A, a bacterial
      uterine flora still persisted in 2 of the cows. At farm B, on the other hand,
      bacterial elimination was complete after 6 weeks. Presence of inflammatory cells
      in uterine histology specimens remained higher at the end of collection and
      resumption of ovarian activity was delayed at farm A. After 7 weeks postpartum,
      only 6 of the 10 cows at farm A had resumed ovarian cyclicity, while at farm B
      the first oestrous cycle had occurred in all cows. The study showed that
      differences regarding uterine infections and their clearance occurred between
      farms and, despite these differences, cows with normal calving performance will
      effectively recover without any treatment.

PMID- 9926457
TI  - Effect of antibiotic growth promoters and anticoccidials on growth of Clostridium
      perfringens in the caeca and on performance of broiler chickens.
AB  - The effects of the growth promoters avoparcin and avilamycin and the ionophore
      anticoccidials maduramicin, narasin and monensin on the growth of Clostridium
      perfringens (Cp) in the caeca and on performance of broiler chickens were tested
      in 2 experiments. The supplements were fed as single feed additives or in some
      combinations. No clinical signs or lesions caused by coccidia were observed in
      any of the studies. All supplements had an antibacterial effect on Cp and
      improved growth rate significantly. Carcass yield of birds fed growth promoters
      avilamycin or avoparcin was significantly higher compared with birds fed
      anticoccidials. These data indicate that, what concerns bird performance, during
      good hygienic conditions supplementation with antibiotic growth promoters may not
      be necessary when the diet is supplemented with an anticoccidial with
      antibacterial effects.

PMID- 9926459
TI  - Interactions between the nematode parasite of pigs, Ascaris suum, and the
      earthworm Aporrectodea longa.
AB  - Pig faeces in which Ascaris suum eggs had been embryonating for 57 days were
      placed in buckets of soil containing either 30 or no earth-worms (Aporrectodea
      longa). When present, earthworms consumed the faeces and transported the eggs
      down into the soil, without inflicting any visible damage on the eggs. In later
      experiments 10 earthworms from the above experiment were fed to each of ten pigs,
      and another 40 earthworms were dissected. None of the 10 pigs became infected
      with A. suum through consumption of earthworms, and none of the dissected
      earthworms were found to contain A. suum larvae. This experiment indicates that
      A. longa did not act as a paratenic host for A. suum but shows that earthworms
      are very efficient in transporting A. suum eggs from faeces deposited on the soil
      surface into the soil.

PMID- 9926458
TI  - The effect of post milking teat dip and suckling on teat skin condition,
      bacterial colonisation, and udder health.
AB  - The teat skin of cows was scored (1: smooth as silk; 2: smooth; 3: slightly
      rough; 4: rough; 5: cracked; and 6: scores) by trained technicians who moved
      their fingers down the barrel of the teat with a light touch. Technicians ranked
      the same population of teats in the same rank order, but their mean values
      differed by half a score which probably could be related to the skin condition of
      their own fingers. Half udder experiments were carried out for 6 months at 4
      farms with 35 to 52 cows each. A postmilking teat spray with 10% glycerol
      improved teat skin condition (p < 0.10) compared with no teat spray. A
      postmilking teat spray with 120 ppm chlorine dioxide did not influence teat skin
      condition compared with no teat spray. No differences in udder health could be
      proven between treatments. Control studies revealed that 10% glycerol as an
      emollient of a postmilking teat spray improved teat skin condition within 3 weeks
      from being slightly rough to being smooth for lactating cows (p < 0.05) but not
      for dry cows having smooth teat skin. Neither glycerol nor chlorine dioxide
      influenced absolute number of bacteria on teat skin after a challenge with
      Streptococcus uberis and Staphylococcus aureus but half life of S. aureus on
      unsprayed teats was longest (p = 0.05). Suckling made teat skin more rough than
      machine milking. Nevertheless, suckling lowered the number of esculin positive
      bacteria on the teat skin. We concluded that the condition of healthy teat skin
      (scores 1-4) has no influence on bacterial colonisation in the absence of cracks
      and sores (scores 5-6).

PMID- 9926460
TI  - Comparison between effects of standard feed and whole wheat supplemented diet on
      experimental Eimeria tenella and Eimeria maxima infections in broiler chickens.
AB  - The effects of experimental infections with Eimeria tenella (Experiment 1, n =
      144) or E. maxima (Experiment 2, n = 216) in broiler chickens fed whole wheat,
      with or without access to grit, as compared to a standard pelleted feed were
      studied. Inclusion of whole wheat was gradually increased up to 30% at 3 weeks of
      age. Grit was given separately. The chickens were kept on litter in a parasite
      free environment with free access to water and feed. At 3 weeks of age half the
      number of chickens were individually inoculated with 500 sporulated oocysts of E.
      tenella (Experiment 1) or 3,000 sporulated oocysts of Eimeria maxima (Experiment
      2), and the remaining birds were kept separate as uninfected controls. Neither
      coccidiostats nor growth enhancers were used. Oocyst concentration was determined
      from each group separately. Intestinal lesions were scored on 6 birds per feed
      regime 7 d postinoculation, and on the remaining birds at slaughter. Diet had no
      significant effect or bird performance during infection. However, there was an
      indication that the E. maxima infection had more negative effect on weight gain
      in birds given standard feed than in those given whole wheat supplement, but the
      difference was not significant (p < 0.09). The number of oocysts shed or mean
      intestinal lesion scores did not differ between diets in either experiment. In
      both experiments, the number of Clostridium perfringens was higher in the caeca
      of inoculated birds, but there were no differences between diets.

PMID- 9926461
TI  - The gastrointestinal bacteria of mink (Mustela vison L): influence of age and
      diet.
AB  - Total numbers of aerotolerant and anaerobic bacteria, and densities of
      Enterobacteriaceae, lactobacilli, staphylococci, salmonella and shigella, and
      campylobacteria were enumerated in the contents of the stomach, small intestine
      (and the associated mucosa), and colon of mink beginning at 2 weeks of age to
      adulthood, and in adults that were fed diets with different levels and types of
      fiber or food deprived. Highest densities of all bacterial groups were found in
      the colon at all ages (up to 10(8) cfu per g for total anaerobes), but were 2-4
      orders of magnitude lower than those of other mammals. When all regions were
      pooled, significant age-related increases (p < 0.05) were detected for anaerobes,
      aerobes, and staphylococci, and these coincided with the dietary shift at
      weaning. Enterobacteriaceae did not vary with age. Lactobacilli were never common
      isolates, but were detected more often after weaning, particularly in adults fed
      diets containing the 2 sources of fiber. Campylobacteria were detected only at 2
      weeks of age, and salmonella and shigella were not isolated from any of the
      experimental mink. Total bacterial densities, the relative proportions of the
      bacterial groups, and age- and diet-related effects differ from those known for
      other mammals, which may be related to the carnivorous diet and rapid movement of
      digesta through the GIT.

PMID- 9926462
TI  - Moxidectin as an endectocide in reindeer.
AB  - During the winter 1991-92, 42 reindeer hinds of the Kaamanen Experimental
      Reindeer Herd in Finnish Lapland, naturally infected with various parasites, were
      allocated to 3 groups. One group was an untreated control group and the other 2
      groups received either moxidectin or ivermectin at a dose of 200 micrograms kg-1
      subcutaneously. The efficacy of treatment was followed with monthly faecal
      examinations for nematode eggs and counting of warbles, Hypoderma tarandi larvae,
      and throat bots, Cephenemyia trompe larvae, from live animals in spring. The
      efficacy of moxidectin against warbles (92.8%) and throat bots (70.8%) did not
      match that of ivermectin, which was 100% against both species. Both moxidectin
      and ivermectin were effective against gastrointestinal trichostrongylid egg
      production over the December to May trial period indicating good efficacy against
      adult and inhibited trichostrongylids. Only non-significant differences were seen
      in weight development and calf birth weights between the groups. Because of its
      only moderate insecticidal efficacy, moxidectin cannot be recommended as an
      endectocide in reindeer.

PMID- 9926463
TI  - Experimental infection of lambs with an equine granulocytic Ehrlichia species
      resembling the agent that causes human granulocytic ehrlichiosis (HGE).
AB  - Five lambs were inoculated with a granulocytic Ehrlichia species originally
      isolated from a Swedish horse with granulocytic ehrlichiosis (EGE). The 16S rRNA
      gene sequence of the Swedish Ehrlichia sp. causing EGE was identical to the
      sequence of the agent causing human granulocytic ehrlichiosis (HGE). After the
      inoculation, infected neutrophils and a low serologic response were seen in all
      lambs, but no clinical symptoms were observed. In one lamb 17% of the neutrophils
      were infected without a corresponding fever. Six weeks later the lambs were
      inoculated with an ovine isolate of E. phagocytophila. After challenge with E.
      phagocytophila the lambs reacted with fever and infected granulocytes. The
      results presented herein show that the equine Ehrlichia isolate was infective for
      lambs but generated weak immune response and no distinctive protection from
      subsequent challenge with E. phagocytophila.

PMID- 9926464
TI  - Effects of melatonin, progestagens, and the ram on out-of-season reproduction in
      Swedish Landrace finewool sheep.
AB  - One hundred twenty-one Swedish Landrace Finewool ewes were treated with
      progestagen sponges (P), teaser ram stimulation (R), or melatonin implants plus
      teaser ram stimulation (M) in preparation for breeding with whole rams in August.
      Blood progesterone analyses from ewes in the R and M groups gave no evidence of
      luteal activity before the introduction of teaser rams. There were no significant
      differences between treatments for pregnancy rate (approximately 90%). The P
      group had the most compact lambing season, while median breeding dates for M and
      R groups were delayed by one cycle. In those groups, the introduction of breeding
      rams was later found to have been too late. M and R differed significantly for
      probable conception date but not for lambing dates. Circa 30% of M ewes did not
      have a short 6 day ovulation cycle after the first ovulation, which resulted in a
      less concentrated lambing season than the other methods. Although no significant
      differences in litter size were seen among the 3 treatments, M had the highest
      group average, 2.25. The ewes in this study were not in very deep anestrous in
      the middle of August. This supports the conclusion that treatment with exogenous
      hormones is not necessary to breed Swedish Landrace Finewool ewes successfully in
      late August/early September.

PMID- 9926466
TI  - [Proceedings of the XLIII National Congress of the French Society of Plastic,
      Reconstructive and Aesthetic Surgery. Paris, France, October 21-23, 1998].

PMID- 9926465
TI  - Ammoniated forage poisoning: concentrations of alkylimidazoles in ammoniated
      forage and in milk, plasma and urine in sheep and cow.

PMID- 9926467
TI  - [Epithelial skin tumors. Anatomo-pathological reminders].
AB  - Epithelial skin tumors are extremely diverse. Benign tumors, which only require
      simple excision, have many pathogenic (hamartomas, virus-induced tumors, etc.) as
      well as anatomical origins (tumors arising from the numerous adnexae of the
      skin). Most malignant tumors are only locally malignant, but some of them have a
      particularly invasive and recurrent behaviour, requiring adapted surgical
      resection. Other tumors present a more marked malignancy and require a more
      complex therapeutic strategy. In every case, surgical resection is an essential
      step in the diagnosis and treatment of these tumors.

PMID- 9926468
TI  - [Facial epitheliomas: general considerations, surgical techniques and
      indications].
AB  - Carcinoma of the face is the skin disease most frequently encountered by plastic
      surgeons in everyday practice. Although basal cell carcinomas and squamous cell
      carcinomas are generally easy to recognize, their treatment remains subject to
      various schools of thought, or even individual practices, which are often
      difficult to define. This article defines a general plan of management of these
      tumours; their histological duality corresponds to a therapeutic duality.
      Resection of a basal cell carcinoma requires safety margins of 3 to 4 mm, versus
      at least 5 mm for a squamous cell carcinoma. In a high-risk subject, with a
      sclerodermiform carcinoma or undifferentiated squamous cell carcinoma, this
      safety margin may be as much as 10 mm or more. Frozen section examination is
      preferable in these situations. Six anatomical regions are studied selectively to
      define the main rules of reconstruction: nasal region, orbitopalpebral region,
      labial region, malar region, frontal region and auricular region. Each region
      will be subdivided into several subterritories, each requiring different
      strategies. The objectives, methods and indications of each reconstruction are
      selectively defined. The final strategy proposed is based not only on the
      author's personal experience, but also on the results of the national survey on
      carcinomas. As a complement to these therapeutic guidelines, the authors raise
      the problem of incomplete resection, which requires the definition of a
      peripheral infiltration index predictive of the recurrence rate. Surgery
      obviously cannot constitute exclusive treatment carcinomas, hence the value of
      presenting other methods currently available in the therapeutic armamentarium.
      Surveillance is essential in every case, determined by the patient's risk of
      recurrence or even metastatic dissemination.

PMID- 9926469
TI  - [National survey on therapeutic strategy in facial epitheliomas].
AB  - The national survey concerning the therapeutic strategy for carcinomas of the
      face published here reviews the therapeutic strategies to this everyday disease.
      The 30 centres included in our statistics have a combined experience of several
      thousand cases. 61% of these centres operate on more than 50 carcinomas per year.
      The following conclusions can be drawn from these data. The general national
      option is for treatment of the defect by flaps than by skin graft, all
      reconstruction situations combined. In the case of skin grafts, the
      retroauricular and supraclavicular sites are the most frequently used. 71% of
      authors also perform skin grafts immediately after the initial resection.
      Directed healing is only indicated in the treatment of small defects with a
      preferential site: the medial canthus. Frozen section examination is requested at
      the time of the initial resection in an average of 24.3% of basal cell carcinomas
      versus 43.9% of squamous cell carcinomas, with a range of 0 to 100% in the two
      series. 16 resection sites were then proposed, to define the most frequent cases.
      Consensus was exceptional. At the very most, a fairly unified strategy was
      defined for defects of the eyelids and lips, where there is a preference for
      classical Abbe or Mustarde flaps for the lower eyelid. Similarly, kite flaps are
      usually preferred in the nasolabial region. In all other cases, the responses
      vary considerably and are submitted to statistical analysis, completed by a
      general discussion.

PMID- 9926470
TI  - [Sclerodermiform basal cell carcinoma. Apropos of a study of 83 cases].
AB  - The authors present a study of 83 cases of sclerodermiform basal cell carcinoma.
      This series constitutes 2.3% of all skin cancers treated in the authors' unit
      from 1981 to 1996. The predominant site of these carcinomas is the centrofacial
      region with 46% of tumours involving the nose. In the majority of cases,
      treatment consisted of cover by a flap (52.6% of cases). Full-thickness skin
      grafts were used in 29% of cases and excision-suture was performed in 18.4% of
      cases. The authors emphasize the need to perform large resection with safety
      margins determined by the macroscopically visible tumour diameter. As frozen
      section pathological examination is not contributive, they prefer to defer
      reconstruction until the final pathology results are obtained. The only exception
      is the need to cover a vital region, such as the eye. These carcinomas must be
      followed in the long-term, as 20% of recurrences were detected in this series,
      comprising many orbitopalpebral sites, associated with difficult staging, and
      which always have a reserved prognosis. The authors therefore propose the use of
      epitheses in so-called high-risk sites. The three main guidelines in this
      disease, one of the most worrying forms of skin cancer, are surgical
      aggressiveness, modesty in terms of the cosmetic result and alertness in the
      follow-up.

PMID- 9926471
TI  - [Advanced epitheliomas of the face: when to stop?].
AB  - Progress in plastic surgery has allowed an ever increasing extension of the
      indications for facial reconstruction. Although carcinomas are now detected
      earlier and earlier, the practitioner is nevertheless faced, several times during
      his working life, with "historical" cases. Although it is fairly rare to observe
      long-term progression of squamous cell carcinomas, basal cell carcinomas can take
      on considerable proportions due to their very low metastatic risk. In these
      situations, the dilemma between conservative management and performing an
      inevitably major procedure is never easy to resolve. Moreover, it is often the
      discomfort experienced by the patient's family which encourages him to accept the
      operation. The objective of the procedure is more often aesthetic rather than
      curative, although this latter objective must always be attempted. Consequently,
      the practitioner should never hesitate to defer reconstruction for several months
      in order to ensure reliable local surveillance. The value of epitheses is clearly
      established in this situation. When a reconstruction can be performed, "major"
      measures are generally necessary, making use of all of the regional or even
      distant plastic surgery techniques used for facial surgery. However, microsurgery
      is a last resort indication, which should only be used when the various pedicle
      flaps have been exhausted. The microsurgical delay technique (Jean-Marie
      Servant's "apple turnover" technique) is particularly useful in these situations.
      In the light of seven clinical cases, the authors try to define the essential
      concepts of this type of management. In fact, the respective limits of active
      intervention and conservative management are defined by each surgeon's common
      sense and experience. The constant improvement of the quality of epitheses make
      them the current treatment of choice for the restoration of extensive defects.
      Lastly, one of the main factors to be considered before taking any treatment
      decision is the psychology of these patients, as it is always difficult to
      explain the discovery of lesions at this advanced stage.

PMID- 9926472
TI  - [Non-melanomatous malignant skin tumors of the hand].
AB  - Non-melanomatous malignant skin tumors of the hand are the same as those observed
      on other parts of the body, but with specific characteristics of frequency,
      aetiology, site and sometimes misleading clinical features. The author analyses
      these characteristics in relation to precancerous tumors: solar keratoses,
      arsenical keratoses, radiation dermatitis, kerato-acanthomas, Bowen's disease and
      malignant tumors: basal cell, squamous cell and other rarer carcinomas. He then
      outlines the principles of surgical treatment with reference to anaesthesia,
      usually local or regional, and resection, whose extent and depth depend on the
      nature and site of the lesion.

PMID- 9926473
TI  - [Malignant melanoma].
AB  - Malignant melanoma is the most serious skin tumor and its incidence is doubling
      every ten years. Ultraviolet rays represent the main environmental cause of
      melanoma. Among the constitutional factors identified, two clinicopathological
      forms of naevus are considered to be important epidemiological precursors:
      acquired dysplastic naevi and congenital giant naevi. Four clinical and
      histological types are distinguished: SSM (Superficial Spreading Melanoma), NM
      (Nodular Melanoma), LMM (Lentigo Maligna Melanoma), arising from Dubreuilh
      melanosis, ALM (Acral Lentiginous Melanoma). Thickness constitutes the essential
      prognostic factor. Clinical examination is the only recommended standard
      assessment. Chest x-ray is useful, and acts as a reference for subsequent follow
      up. Other complementary investigations are requested as a function of clinical
      signs. Treatment is exclusively surgical. The lateral resection margins are 0.5
      cm for melanoma in situ, 1 cm for melanomas less than 1 mm thick, 2 cm for
      melanomas between 1 and 4 mm thick, and 3 cm for melanomas thicker than 4 mm.
      Chemotherapy is mainly used in the treatment of metastatic melanoma. There is no
      indication for radiotherapy apart from palliative treatment of nonsurgical
      metastases. New therapies such as immunotherapy and gene therapy are under
      investigation.

PMID- 9926474
TI  - [Cutaneous and subcutaneous sarcomas].
AB  - Cutaneous sarcomas are uncommon tumors presenting many histological types. The
      diagnosis is based on pathological, immunohistochemical and sometimes
      ultrastructural studies. The development of cytogenetic and molecular analysis
      may constitute an additional aid to the diagnosis and classification. Prognosis
      and therapeutic strategies are established on the basis of various criteria using
      different types of staging and grading, but these classifications have not yet
      been standardized. The rarity of cutaneous sarcoma, and the diversity of clinical
      presentations account for the difficulties of management, which requires a
      multidisciplinary approach.

PMID- 9926475
TI  - [Merkel cell carcinoma].
AB  - Merkel cell carcinoma (MCC) is a malignant cutaneous neuroendocrine tumor which
      may be difficult to diagnose. It mostly occurs in old patients and the commonest
      sites are the skin of the head and neck and the extremities. MCC appears as a
      solitary violaceous dome-shaped nodule or indurated plaque. Histopathologic
      diagnosis may be difficult and three main patterns have been described. With
      immunohistochemistry studies, MCC express both epithelial (cytokeratins, EMA) and
      neuroendocrine (NSE, chromogranin, ...) markers. The tumor develops an aggressive
      course not unlike an aggressive melanoma. Local recurrence and regional lymph
      node metastases occur in 40 to 75% of cases. Long-term prognosis is unfavorable
      (3-year survival rate is 55%). Wide surgical excision associated with
      radiotherapy is the treatment of choice, regional lymph node metastases should be
      treated by lymph node excision and radiotherapy; chemotherapy should be used in
      systemic disease.

PMID- 9926476
TI  - [Cutaneous manifestations of type 1 neurofibromatosis and their treatment].
AB  - After recalling the frequency and pathophysiology of type 1 neurofibromatosis, or
      Von Recklinghausen disease, the authors report the various cutaneous
      manifestations: cafe-au-lait spots, lentigines, cutaneous neurofibromas,
      plexiform neurofibromas. Treatment must be multidisciplinary, as surgery is
      difficult and often gives disappointing results. The various surgical treatments
      are considered according to the type and site of the lesions to be treated, with
      particular emphasis on the treatment plan, which must be discussed with the
      patient.

PMID- 9926477
TI  - [Vascular "tumors" and the rules of their surgical management].
AB  - After defining vascular tumors and malformations, formerly called angiomas, the
      authors adopt the classification of the International Society for the Study of
      vascular Anomalies. The various groups of malformations, after definition of the
      subject and the problems raised, are illustrated by a number of clinical cases
      and the rules of surgical management are discussed. Capillary malformations,
      formerly called portwine stains, can be treated by dye laser, but sometimes
      tissue and orthognathic reconstructive surgery in the presence of a skeletal
      malformation. Lymphatic malformations (lymphangiomas), optimally assessed by CT
      or MRI, can be treated by a variety of approaches: sclerotherapy, surgery. Venous
      malformations raise very different problems in the cervicocephalic region and on
      the limbs and trunk, but always require a multidisciplinary approach with,
      according to the site, size and repercussions, Ethibloc percutaneous
      sclerotherapy, embolization, surgery. Arteriovenous malformations require
      complete surgical treatment, usually preceded by embolization; reconstruction
      consists of local flaps or skin expansion in simple cases, and revascularized
      free flaps in difficult cases. If the malformation is cosmetically and
      functionally acceptable, the authors propose conservative management. The first
      line treatment of haemangiomas is pharmacological (corticosteroids, interferon),
      but surgery may be indicated in two situations: early and late. There is a
      renewed interest in early surgery, subtended by several factors including
      cosmetic concerns and the development of new technologies, including the
      Cavitron. Late surgery retains its classical cosmetic and functional indications.
      Two key-words dominate the rules of therapeutic management of all types of
      vascular malformations: a multidisciplinary approach and modesty.

PMID- 9926478
TI  - Cognitive impairment in elderly, non-insulin dependent diabetic men in
      Bangladesh.
AB  - This was a case-comparison study to determine whether there was any association
      between non-insulin dependent diabetes mellitus (NIDDM) and cognitive impairment
      in subjects over the age of 65 years. Forty-eight non-insulin dependent diabetic
      males were compared with eighteen non-diabetic age & sex-matched controls. There
      was significantly higher cognitive impairment in the diabetic group compared to
      the control group when cognitive function was tested using the Mini-Mental State
      Examination (MMSE). However, after adjustment for confounding variables such as
      hypertension and cerebrovascular diseases there was no significant association
      between NIDDM per se and cognitive impairment. Other risk factors of cognitive
      impairment may be investigated.

PMID- 9926479
TI  - Misuse of drugs in acute diarrhoea in under-five children.
AB  - This was a community based, thirty cluster survey, carried out in Chittagong
      metropolitan area of Bangladesh, aimed to determine the extent of misuse of drugs
      in acute diarrhoea among under-five children. Data were collected from 360
      mothers whose under-five children had suffered from acute diarrhoea during the
      preceding two weeks of interview. Data were pertained to type and duration of
      diarrhoea and treatment received. There were 339(94.2%) cases of acute watery
      diarrhoea and 21 (5.8%) cases of dysentery i.e. blood in stool. The mean duration
      of the diarrhoeal episode was 3.17 +/- 1.69 days (95% CI, 2.99-3.34). Three
      hundred twenty eight (91.1%) cases received treatment. There was a total of 401
      consultations, out of which 328(81.8%) had first, 69(17.2%) had second and
      4(1.0%) had third consultations. The first and second treatment were provided
      predominantly by care-providers (43.3%) and physicians (5.5%) respectively. Only
      82(26.7%) cases of acute watery diarrhoea received WHO recommended treatment and
      only 5(23.8%) cases of dysentery received appropriate antibiotics. The rest
      241(73.5%) cases received inappropriate treatment either antibiotic or drugs
      other than WHO recommendation. The average number of drugs prescribed per patient
      was 1.5 during the episode. The commonly prescribed drugs were metronidazole
      (38.6%) and antibiotics (17.3%). Those who consulted health professionals were at
      5.7 times higher risk of receiving drugs. The mean duration of the episode of
      acute watery diarrhoea was increased significantly when drug is used in the
      treatment. It is concluded that there was high prevalence of misuse of drugs in
      the treatment of acute diarrhoea among under-five children which calls for
      intervention to improve the prescribing pattern as per WHO recommendation.

PMID- 9926480
TI  - Lateral femoral cutaneous nerve block for split skin grafting.
AB  - Wound with loss of skin needs grafting for early healing and to prevent deformity
      and disability. For skin grafting lateral femoral cutaneous nerve block can be
      used as regional anesthesia. The efficacy of 55 lateral femoral cutaneous nerve
      block was assessed in 52 patients of 10 to 70 years of age. The nerve block was
      found effective in all cases. 90.91% showed excellent results. The procedure
      seemed to be easy, safe and less costly for the purpose of skin grafting.

PMID- 9926481
TI  - Cerebral malaria--a study of 104 cases.
AB  - One hundred and four adult cases of cerebral malaria (73 male, 31 female) were
      studied between July 1995 to June 1996 in Chittagong Medical College Hospital.
      Diagnosis of cerebral malaria was based on unrousable coma or any neurological
      manifestation in a febrile patient with asexual Plasmodium falciparum in blood
      film. Intermittent fever (83%), vomiting (80%), headache (75%), convulsion (60%)
      and history of travel or residence in malaria endemic area were important
      features noted in patients with cerebral malaria. Most of the patients (69%) were
      admitted within 25 to 48 hours following unconsciousness. The factors are more
      common in cases with high mortality with diastolic blood pressure (DBP) below 60
      mm of Hg, anaemia, persistence of Glasgow Coma Score below 5 on day 2, high
      parasite count at presentation, proteinuria and high level of serum urea. Out of
      104 cases of cerebral malaria 66 patients (63.5%) recovered without sequelae, 34
      patients (32.7%) died and 4 patients (3.8%) recovered with some residual
      sequelae. Establishment of intensive care unit in tertiary level hospitals is
      necessary to take appropriate measure for severe cerebral malaria cases for
      reduction of mortality.

PMID- 9926482
TI  - Magnesium sulphate versus diazepam in the management of eclampsia.
AB  - This clinical trial was conducted to compare the anticonvulsant response of
      magnesium sulphate and diazepam in the management of eclampsia. The study was
      carried out at the eclampsia unit of Dhaka Medical College Hospital during the
      period from October, 1995 to January, 1996. Two hundred consecutive admitted
      patients were recruited for the study and randomly assigned to two treatment
      groups: magnesium sulphate and diazepam. One hundred patients received injection
      magnesium sulphate and another one hundred received injection diazepam. All
      patients of both the group were matched for baseline characteristics. Convulsion
      was controlled in 95% of the patients of magnesium sulphate group and 74% of the
      patients of diazepam group (p < .0005). The mean controlling time is also
      significantly lower in magnesium sulphate group than diazepam group (8.50 hours
      vs 9.39 hours). Patients of magnesium sulphate group regain consciousness much
      earlier (mean time 20.62 hrs.) than the patients of diazepam group (mean time
      40.62 hrs.). No significant difference was observed in controlling blood pressure
      and foetal outcome. The study finding shows that magnesium sulphate has some
      advantage over diazepam in controlling convulsion and regaining consciousness. If
      magnesium sulphate can be made available in the market by local production it may
      be recommended to use this drug in the primary health care without any hazzard
      before referring to other hospital.

PMID- 9926483
TI  - Incidence of low birth weight in three selected communities of Bangladesh.
AB  - This prospective study was conducted in urban affluent, slum and rural
      communities of Bangladesh during Feb '94 to Feb '95. From each community, 250
      pregnant mothers were recruited in the study and at the end total 660 live births
      were studied to determine the incidence and risk factors of low birth weight.
      Incidence of low birth weight was highest in urban slum (36.8%) followed by rural
      area (20.9%) and lowest in urban affluent community (18.3%). The area of
      residence had a significant influence on birth weight suggesting that
      environmental stress had detrimental effect on birth weight. Age, weight and
      height of mothers were also risk factor for low birth weight of their babies.
      Mothers of less than 20 years and more than 35 years, weighing less than 40 kg
      and having height less than 140 cm had the higher risk of giving birth to low
      birth weight babies. Incidence of low birth weight was highest (73.2%) among the
      primigravidae mothers and 36.8% among the mothers who had no antenatal check-up,
      but it was 15.9% among those who had check-up more than 7 times. The distribution
      of low birth weight babies was higher (48.2%) among the mothers who had never
      gone to school. To reduce the incidence of low birth weight, upliftment of socio
      economic condition has got no alternative which is very much related to education
      level of the people. Emphasis should be given on mothers' education which is one
      of the influencing factors of birth weight of babies.

PMID- 9926484
TI  - Aggressive treatment of early rheumatoid arthritis to prevent joint damage.

PMID- 9926485
TI  - Haemophilus influenzae type B disease at 11 pediatric centres, 1996-1997.

PMID- 9926486
TI  - Varicella-related deaths among children--United States, 1997.

PMID- 9926487
TI  - The 50th anniversary of WHO.

PMID- 9926488
TI  - 1997-1998 influenza season: Canadian laboratory diagnoses and strain
      characterization.

PMID- 9926489
TI  - Outbreak of cryptosporidiosis associated with a water sprinkler fountain-
      Minnesota, 1997.

PMID- 9926490
TI  - Canada's International Immunization Initiative.

PMID- 9926491
TI  - AIDS: focus on youth.

PMID- 9926492
TI  - The impact of embarrassment on condom purchase behaviour.

PMID- 9926493
TI  - A survey of food problems experienced by Toronto street youth.
AB  - A brief survey was undertaken to assess the nature and severity of food scarcity
      experienced by a sample of 88 street youth in downtown Toronto, and to identify
      markers of vulnerability to food scarcity. Almost half of the youth reported
      experiencing involuntary hunger or food deprivation during the previous 30 days.
      Youth who were literally homeless (i.e., on the street or "squatting" in
      abandoned buildings) and those relying primarily on street-based activities for
      income appeared particularly vulnerable to food deprivation. Although limited in
      scope, the findings raise questions about the nutritional well-being of street
      youth and highlight the need for more effective interventions to address problems
      of poverty, hunger, and homelessness among Canadian youth.

PMID- 9926494
TI  - [Hard-to-reach young mothers: study of the implementation of a pre and postnatal
      intervention for a clientele at risk].
AB  - This paper describes the implementation of a project to prevent the negative
      biopsychosocial outcomes of teenage pregnancy. The purposes of this project were
      1) to reach, as early as possible, young women under 20 years, either pregnant or
      already young mothers, living in the downtown area of Quebec city on the fringe
      of society, and perceived to be at risk, and 2) to develop their capacities to
      take care of themselves and their children, by helping them to recognize their
      needs, to use adequately the available resources, and to break out of their
      isolation. A team from Le Centre jeunesse de Quebec worked with 25 young pregnant
      women and 3 young mothers, over a period of 21 months. This team provided the
      women and their children with a continued and individualized follow-up, which
      allowed them to develop their autonomy.

PMID- 9926495
TI  - Public health responses to health inequalities.

PMID- 9926496
TI  - A review of a prison cervical cancer screening program in British Columbia.
AB  - OBJECTIVE: To review a 1995 Pap smear screening program at Burnaby Correctional
      Centre for Women (BCCW). METHOD: 129 inmates (15%), were screened in BCCW in
      1995. General population data were obtained from the British Columbia Cervical
      Cytology Screening Program (BC CCSP) Registry. RESULTS: BCCW inmates aged 25-29
      years were 11 times more likely to have high grade cytologic abnormalities on Pap
      smear screening compared with age-matched general population (p < 10(-10). In the
      20-34 year age group, 47% of BCCW inmates had received at least one Pap smear in
      1992-1994, compared with 87% of the general population (p < 0.001). There was no
      relationship between Pap smear results and BCCW inmate ethnicity (p = 0.85).
      CONCLUSIONS: Prison inmates presented with more severe abnormalities on Pap smear
      screening at a younger age, and had received Pap smear screening less frequently,
      compared with the general population.

PMID- 9926497
TI  - Cluster of unintentional carbon monoxide poisonings presenting to the emergency
      departments in Kingston, Ontario during 'ice storm 98'.

PMID- 9926498
TI  - Prevention of paediatric acquired brain injury: an interactive, elementary-school
      program.
AB  - Responding to a gap in existing programs that aim to prevent spinal cord and
      brain injuries among children, an interactive activity-based program was
      developed and implemented through local elementary schools, focusing on children
      8 to 10 years of age. Evaluation involved a pretest/post-test design with a
      comparison group who had not experienced the program. Children who participated
      in the program showed increases in knowledge, self-reported changes in behaviour,
      and favourable shifts in attitudes about vulnerability to injury four months
      after exposure to the program. Control group children responded similarly to how
      children in the intervention group responded on the pretest measure.

PMID- 9926499
TI  - Injury in Canadian youth: a secondary analysis of the 1993-94 Health Behaviour in
      School-Aged Children Survey.
AB  - OBJECTIVES: 1) To describe patterns of injury among Canadian youth, and 2) to
      explore whether injured youth can be characterized by adverse lifestyle factors.
      DESIGN: Secondary analysis of the Canadian 1993-94 Health Behaviour in School
      Aged Children Survey (youth enrolled in grades 6, 8 and 10). PRIMARY: OUTCOME:
      Physical injuries that occurred in the twelve months prior to survey. RESULTS:
      Each year, 36% of these Canadian youth experience at least one injury. Risks vary
      by grade, gender and cause of injury. When extrapolated to the Canadian
      population, more than 600,000 injuries are experienced by youth annually. Sports
      injuries and accidental falls were leading contexts of injury. There was only
      limited evidence to suggest that high-risk youth can be characterized by adverse
      lifestyle behaviours. CONCLUSIONS: Injuries to youth are a major public health
      problem. Ongoing surveillance is required in Canada. Future editions of this
      survey will, in part, address this need.

PMID- 9926500
TI  - Modelling the community as a determinant of health.
AB  - Widespread recognition is given to the idea that an individual's health is
      influenced by the ways an individual works, rests and plays as well as genetic
      endowments. More recently, some researchers have suggested that the relationships
      between individual 'characteristics' and health are influenced by the context or
      community of the individual. Although the notion of the community as a
      determinant of health is not new, the incorporation of the community in empirical
      research on the determinants of health has been based on simple statistical
      models that fail to reflect the complex nature of the individual-community
      interface. In this paper we use the methods developed in educational research to
      show how separate statistical models for variations in health between communities
      and between individuals can be combined to provide a multi-level model for the
      determinants of health of populations.

PMID- 9926501
TI  - Community-based heart health promotion: perceptions of facilitators and barriers.
AB  - This paper examines factors that facilitate or impede the implementation of heart
      health activities in Ontario public health departments using survey (n = 262) and
      depth interview (n = 56) data from Canadian Heart Health Initiative-Ontario
      Project (CHHIOP). The data were consistent in revealing factors related to
      leadership, staffing, resources, internal organization, and characteristics of
      the surrounding community as the primary facilitators or barriers. Diversity
      within these common themes reflected variation due to external factors in the
      communities served by the health unit and factors internal to the health unit
      itself. The findings advance knowledge of the factors that influence
      predisposition and capacity to undertake community-based heart health promotion
      in public health departments, and they underscore the challenge of achieving
      integrated programs among partner agencies.

PMID- 9926502
TI  - Heart health promotion: predisposition, capacity and implementation in Ontario
      Public Health Units, 1994-96.
AB  - The Canadian Heart Health Initiative-Ontario Project (CHHIOP) investigates
      predisposition and capacity in Ontario public health departments to implement
      community-based heart health promotion activities. The research draws upon
      diffusion of innovations theory and recent work on ecological approaches to
      health promotion within which public health agencies are seen to play a central
      role. Mail-back surveys were completed by heart health staff in all 42 health
      departments in 1994 and 1996. Predisposition and capacity were measured as the
      importance and effectiveness ascribed to 18 organizational practices supportive
      of community heart health activities. Level of implementation was reported for 74
      activities spanning a range of risk factors and settings. Predisposition,
      capacity and implementation scores increased between 1994 and 1996. The findings
      confirm positive correlations between predisposition and capacity and between
      capacity and implementation.

PMID- 9926503
TI  - Influenza vaccination of high-risk children: a survey of three physician groups.
AB  - OBJECTIVE: To determine the variability in physician knowledge, attitudes, and
      behaviours in relation to influenza vaccination of children. METHOD: A 17-item
      cross-sectional questionnaire, with follow-up mailings to non-responders, was
      mailed to a random sample of 100 family physicians and 100 community
      pediatricians within Metropolitan Toronto and all 130 subspecialists at The
      Hospital for Sick Children, Toronto. RESULTS: Of 315 eligible physicians, 243
      (77%) responded. Of the three groups, community pediatricians were more likely
      than either family physicians or subspecialists, to recommend vaccination for all
      but one of the high-risk conditions. Pediatricians (54%) were also the most
      likely to use active strategies to contact families of high-risk children
      compared with family physicians and subspecialists (both 23%). Only 44% of all
      physicians were themselves vaccinated against influenza. CONCLUSIONS: Influenza
      vaccination is recommended by most physicians; however, the responsibility for
      vaccination appears to fall to those in the community. Physician education plus
      further research and a review of provincial strategies for improving vaccination
      are needed.

PMID- 9926504
TI  - Prevalence of low and high birthweight among the James Bay Cree of northern
      Quebec.

PMID- 9926505
TI  - Stages of physical activity in the Alberta population.

PMID- 9926506
TI  - Reducing economic disparity to achieve better health: modelling the effect of
      adjustments to income adequacy on self-reported morbidity among the elderly in
      Canada.
AB  - Class differentials in health have been documented extensively in the
      sociological literature of the past two decades. Although sociologists have been
      concerned with analyzing the relationship between social class and health, less
      attention has been paid to modelling the effects of minimizing social disparities
      on health outcomes. From a sub-sample (N = 1,943) of elderly respondents aged 65
      and over, four logistic regression equations where income adequacy was shown to
      be correlated with morbidity were selected. By adjusting the scores on the income
      adequacy variable, we were able to model the effect of shifting individuals from
      lower to higher income groups. The most dramatic results were obtained after all
      respondents were shifted into the highest income adequacy classification. A more
      realistic hypothetical model, the transfer of individuals from the lowest income
      group to the next category, produced the least attractive reduction in morbidity.
      Obviously, income adjustment alone is insufficient. Findings are discussed in
      terms of interventions to prevent economic disparity in old age.

PMID- 9926507
TI  - Role of bacterial colonization in neonatal necrotizing enterocolitis and its
      prevention.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in
      premature infants. A major component of the pathophysiology of NEC is the nature
      of the interaction of bacteria with the premature gut. Intestine microflora are
      important to the host in resistance to bacterial infections. Diet and
      environmental conditions can influence this ecosystem. A breast-fed full-term
      infant has a preferred intestine microbiota in which bifidobacteria predominate
      over the potentially harmful bacteria, whereas in formula-fed infants coliforms,
      enterococci and bacteroides predominate. The pattern of bacterial colonization in
      the premature neonate gut is quite different from that in the gut of the healthy
      full-term infant. Those infants requiring intensive care acquire intestinal
      organisms slowly, and the establishment of bifidobacterial flora is retarded. A
      delayed bacterial colonization of the gut with a limited number of bacterial
      species tends to be virulent. Bacterial overgrowth is one of major factors
      promoting bacterial translocation. The aberrant colonization of the premature
      infant may contribute to the development of NEC. Breast feeding protects infants
      against NEC. Oligosaccharides and glycoconjugates, natural components in human
      milk, may prevent intestinal attachment of enteropathogens by acting as receptor
      homologues. Probiotics and prebiotics modulate the composition of human intestine
      microflora to the benefit of the host. The beneficial effects may result in the
      suppression of colonization of harmful microoganisms and/or the stimulation of
      bifidobacterial growth. In the future, control and manipulation of bacterial
      colonization in the neonate gut may be a new approach to the prevention and
      treatment of bacterial intestinal disease of various etiologies.

PMID- 9926508
TI  - Hepatocellular carcinoma in children.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in
      humans. Although it occurs mainly in adults of 40 to 60 years of age, it may
      develop in children. It mainly occurs in children older than six years of age,
      with male predominance. Children with chronic hepatitis B virus (HBV) infection
      and underlying metabolic diseases are the two main high risk groups for childhood
      HCC. HBV infection is the main cause of childhood HCC in areas hyperendemic for
      HBV infection. In Taiwan, nearly 100% of HCC children were hepatitis B surface
      antigen seropositive. Maternal transmission (94%) is the most important route of
      transmission of HBV infection in HCC children. For HBV related HCC in children,
      immunization is the most effective way for the control of childhood HCC. The
      first universal vaccination against HBV in the world was launched in Taiwan in
      July 1984. The prevalence of hepatitis B surface antigenemia in children declined
      from 10% in 1984, prior to the vaccination program, to < 1% in 1994, 10 years
      after the implementation of the program, in children less than 9 years of age.
      The annual incidence of HCC in children aged 6 to 9 years of age also decreased
      from 0.52 per 100,000 born in 1974-1984 to 0.13 per 100,000 born in 1984-1986.

PMID- 9926509
TI  - The effect of povidone-iodine on thyroid function of neonates with different
      birth sizes.
AB  - The aim of this study was to elucidate the role of povidone-iodine (PV-I) on
      thyroid function of newborns with different birth sizes in a high iodine-intake
      city. Serial measurements of serum thyroxine (T4) and thyrotropin (TSH) levels
      were done in 44 newborns locally treated with 10% PV-I for insertion of
      percutaneous central venous catheters. The results showed that the thyroid
      function was influenced prominently in very-low-birth weight (VLBW) babies. TSH
      went significantly higher after application of PV-I for 48 hours in VLBW babies.
      The smaller the babies were, the lower the T4 at birth and thereafter. In
      conclusion, PV-I is suggested to be avoided for single application on a wide skin
      surface in VLBW babies, even in an area with high iodine-intake population.

PMID- 9926510
TI  - Urinary bladder outlet obstruction in children.
AB  - Bladder outlet obstruction, either functionally or structurally, could lead to
      bladder trabeculation, vesicoureteric reflux, hydronephrosis and, eventually, to
      renal parenchymal damage. If no treatment is given, end-stage renal failure will
      ensue. The cases of 17 patients of bladder outlet obstruction at National Taiwan
      University Hospital from 1984 to 1997 were reviewed. Initial presentation,
      etiology and treatment were discussed. Nine patients were victims of neurogenic
      bladder and two patients were victims of nonneurogenic neurogenic bladder. Four
      patients suffered from posterior urethral valve. Ureterocele and urethral
      rhabdomyosarcoma were noted in one case each. The most common clinical
      manifestation was urinary tract infection. Ultrasonography, urodynamic study and
      voiding cystourethrogram were used to delineate the cause and help to decide the
      appropriate treatment. In conclusion, early detection and prevention of
      deteriorated renal function are important for children with urinary bladder
      outlet obstruction.

PMID- 9926511
TI  - The relationship between serum and saliva erythropoietin concentrations in
      adults, full-term and premature infants.
AB  - Simultaneous blood and saliva samples were collected for determination of the
      relationship between serum and saliva erythropoietin (EPO) concentrations in 12
      adults (Group I), 15 full-term neonates (Group II), and 11 premature infants
      (Group III). Saliva was collected with a modified sputum-collecting tube combined
      with a vacuum suction pump. Serum and saliva EPO concentration was measured by
      enzyme-linked immunosorbent assay. The relationship between serum and saliva
      concentrations was explored using (1) regression analysis and (2) serum-to-saliva
      ratio. Salivary concentrations approximated 15 to 30% of the serum concentrations
      based on the serum-to-saliva ratios. Significant correlation was observed between
      serum and salivary concentrations in each group (p < 0.05). The regression
      analyses produced formulas for predicting serum EPO concentrations from saliva
      EPO concentrations which seemed to fit the data well. The resulting formula is
      surprisingly consistent with that derived from Group I. The ratio models seem to
      fit the data well as regression models. From the results it is concluded that the
      use of salivary samplings for serum EPO in adults, full term and premature
      infants may be a possible alternative method to blood samplings.

PMID- 9926512
TI  - Plasma alkaline phosphatase activity in children and adolescents.
AB  - From February to June in 1996, there were 47,800 students for health examination
      in Taichung City, Taiwan. The population consisted of the first and fourth
      graders of primary schools and the first grader of junior high schools. We
      selected 3,452 healthy students for further study by two stage sampling. In this
      report, 52.5% of the students were boys, and 47.5% of the students were girls.
      The mean age of students was 9.9 +/- 2.4 years. Girls at age 7 and age 10 had
      higher activity of alkaline phosphatase than boys at the same age. The peak of
      alkaline phosphatase activity in girls occurred at age 10. Alkaline phosphatase
      activity was significantly related to weight-length index by multiple regression
      analysis (p < 0.05). Although clinical application as an obesity factor still
      needs further investigation, in the future it may be well to routinely check this
      enzyme when assessing childhood obesity.

PMID- 9926513
TI  - Levels of gonadotropins and adrenocortical hormones in newborns.
AB  - We established reference ranges of serum gonadotropins, testosterone, 17
      hydroxyprogesterone, aldosterone and renin in order to evaluate the causes of
      abnormal genitalia in Taiwanese newborns. Random serum samples were obtained from
      60 full term newborns aged 3 to 5 days and the mean birth weight was 3.35 +/-
      0.25 kg. The concentrations of follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), total testosterone, 17-hydroxyprogesterone, aldosterone and renin
      were measured by radioimmunoassay. Mean FSH, LH, testosterone, 17
      hydroxyprogesterone, aldosterone and renin were 0.61 +/- 1.13 IU/L, 2.95 +/- 2.72
      IU/L, 0.70 +/- 0.47 ng/mL, 3.32 +/- 2.13 ng/mL, 795.73 +/- 511.36 pg/mL and 31.43
      +/- 27.30 pg/mL, respectively. Significantly higher levels of testosterone (p <
      0.05) were found in male than in female infants. Serum levels of FSH were
      significantly higher in female newborns (p < 0.05). There was no significant
      difference in the serum levels of LH between male and female infants. This study
      provides reference ranges of serum gonadotropins and some of the adrenocortical
      hormones in newborns.

PMID- 9926514
TI  - Symptomatic hypomagnesemia in children.
AB  - Between January 1996 and June 1998, 24 children with symptomatic hypomagnesemia
      were enrolled for analysis of their symptomatology, causes, and treatment
      outcome. Hypocalcemia and hyperphosphatemia suggesting impaired parathyroid
      function were the most common electrolyte disorders. Hypokalemia was also
      frequently noted. The related symptoms including seizure, tetany, and weakness
      were common. Drug-induced renal magnesium wasting was the most common cause of
      symptomatic hypomagnesemia, and tended to occur in older children using
      aminoglycoside, furosemide, and amphotericin-B. The associated gastrointestinal
      causes might add a minor contribution to the development of hypomagnesemia.
      Analyses of PTH levels in 13 children suggested that inhibition of PTH synthesis
      or secretion was responsible for hypomagnesemic hypocalcemia in most patients.
      However, peripheral PTH resistance might also account for the mechanism in a few
      patients. In most patients, symptomatic hypomagnesemia was transient, and
      improved after magnesium provision. Only one child with congenital renal
      magnesium wasting and two with primary hypomagnesemia needed long-term magnesium
      treatment.

PMID- 9926515
TI  - FISH analysis in both classical and atypical cases of Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder,
      characterized by distinct facial changes, growth deficiency, mental retardation,
      supravalvular aortic stenosis (SVAS)/peripheral pulmonary stenosis, and
      associated at times with infantile hypercalcemia. A pilot study has been carried
      out to assess the reliability of the detection of hemizygosity at the elastin
      locus by fluorescence in situ hybridization (FISH) analysis as a diagnostic test
      in both classical and atypical WBS. Eight subjects with classical WBS and four
      others in whom a diagnosis could not be confirmed on clinical criteria alone were
      enrolled. In the classical WBS group, five (5/8) had a visible interstitial
      7q11.22-11.23 deletion detected by high-resolution banding, and all (8/8) had a
      submicroscopic deletion of the elastin locus on chromosome 7 by FISH analysis. In
      the atypical WBS group, only one (1/4) had elastin deletion. The other three,
      with isolated SVAS, had normal development and minimal signs of WBS. Furthermore,
      the patients with microscopic 7q11.22-11.23 deletion have more associated
      features of WBS than those without visible interstitial deletions by high
      resolution banding. These results, therefore, emphasize the importance of a
      combined high-resolution and molecular cytogenetic (i.e., FISH) approach to
      diagnosis and suggest that the degree to which microscopic/submicroscopic
      deletions of chromosome 7 extending in beyond the elastin locus may explain some
      of the phenotypical variability found in WBS.

PMID- 9926516
TI  - Pemphigus vulgaris.
AB  - Pemphigus vulgaris is an autoimmune vesiculobullous disease of the skin and the
      mucous membrane. It most commonly involves the population of the fifth and sixth
      decades, and is extremely rare in children. We report a case of this disease in a
      13-year-old boy, who was documented to have pemphigus vulgaris with historical,
      histopathological, and immunological criterion. He received corticosteroid and
      immunosuppressive drugs and a good response was achieved. We concluded that
      pemphigus vulgaris is a rare disease in children, but it should be kept in mind
      as a differential diagnosis of oral ulceration along with skin manifestation in
      children.

PMID- 9926517
TI  - Severe combined immunodeficiency with B-lymphocytes (T-B+SCID): report of two
      cases.
AB  - Severe combined immunodeficiency (SCID) is a rare pediatric medical emergency in
      Taiwan. The early diagnosis of infants with SCID is very important because it can
      save the life of these critical infants. The essential clues important for early
      diagnosis of SCID patients include positive family history of early infant death,
      paucity of tonsil and lymphoid tissue, cutaneous fungal infection and
      lymphopenia. Severe combined immunodeficiency is a heterogeneous group of
      inherited disorders characterized by the failure of both cellular and humoral
      immunity. It can be categorized into SCID with B-lymphocytes predominant (T
      B+SCID) and SCID with paucity of B-lymphocytes (T-B-SCID), according to the
      number of B-lymphocytes in the patient's peripheral circulation. We report two
      male infants with T-B+SCID who had been suffering from severe pulmonary distress
      with persistent O2 desaturation when they were transferred to our pediatric
      intensive care unit. Tracing back these infant's family histories, it was
      discovered that both of them had an elder brother who had died to overwhelming
      infection within the first year of life, and Pneumocystis carinii pneumonitis
      (PCP) was confirmed in the elder brother of case 2. After hospitalization, the
      immune condition of these two infants were evaluated which showed a decrease in T
      cell and NK cell number, an increase in B-cell number, and decreased serum levels
      of all the Igs except IgM, which was elevated in case 1. These were the
      diagnostic immunological findings for T-B+SCID, which included X-linked SCID and
      Jak-3-deficient SCID. During hospitalization, severe mucocutaneous candidiasis
      and PCP were noted and confirmed in case 1 and PCP was highly suspected in case
      2. Bone marrow transplantation, the only curable treatment for T-B+SCID at
      present, could not be performed in these two patients because of their grave
      clinical condition. Both of them expired due to their progressively downhill
      pulmonary conditions.

PMID- 9926518
TI  - Harlequin ichthyosis: report of one case.
AB  - Harlequin ichthyosis, or harlequin fetus, is a relatively rare, severe form of
      congenital ichthyosis. Although the clinical features have been well described,
      very little is known about the pathogenesis, clinical course, appropriate
      treatment and prognosis of harlequin ichthyosis because most of these babies with
      harlequin ichthyosis die within a few weeks of life. We herein report a case of
      harlequin ichthyosis, which we believe is the first such case in Taiwan.

PMID- 9926519
TI  - Group A streptococcal necrotizing fasciitis after varicella: report of two cases.
AB  - The most common complication in children with varicella is cutaneous superimposed
      infection with pyogenic bacteria. The association between varicella and group A
      beta-hemolytic streptococci (GABHS) necrotizing fasciitis has been recorded for
      over 50 years. Two cases with the specific problems are presented here together
      with a review of the literature. This infection is caused by GABHS superinfection
      of the skin lesions due to chickenpox. It can be unrecognized or late-diagnosed,
      with fatal consequences. Because of prompt recognition and aggressive surgical
      and medical treatment, the two patients survived without loss of the affected
      limb.

PMID- 9926520
TI  - Use of a concurrent operants paradigm to evaluate positive reinforcers during
      treatment of food refusal.
AB  - The authors evaluated the responsiveness of 4 preschool-aged children to positive
      reinforcers within a concurrent operants paradigm during mealtimes. The children
      were presented with two identical, concurrently available sets of food. Each set
      differed in quantity and quality of positive reinforcement paired with acceptance
      of each bite of food or in the number of bites of food required to obtain
      positive reinforcement. Experiment 1 evaluated 1 child's responsiveness to
      positive reinforcement while permitting escape from bite offers. Experiment 2
      evaluated 2 children's responsiveness to positive reinforcement when escape
      extinction occurred. Results from these experiments suggested that the children
      were responsive to positive reinforcers and chose more often the bites paired
      with the greater quantity and/or quality of reinforcement. Experiment 3 evaluated
      1 child's responsiveness to positive reinforcement both without and with escape
      extinction. Results suggested that positive reinforcement affected choice
      behavior and that escape extinction affected amount of food consumed.

PMID- 9926521
TI  - Identifying critical social interaction behaviors among high school students with
      and without disabilities.
AB  - This article describes an investigative process used to identify critical
      behaviors that relate to social interaction among high school students with and
      without disabilities. A series of studies resulted in the identification of six
      empirically and socially validated conversational behaviors that could serve as
      targets of interventions designed to increase social interaction. Findings also
      indicated that little social interaction occurred among high school students with
      and without mental retardation in the absence of programming or supports.
      Implications of the findings are discussed as well as suggestions for future
      research. Finally, a model for social skills interventions is proposed that may
      result in increased social interaction among students with and without
      disabilities.

PMID- 9926522
TI  - Recall and validation of phobia origins as a function of a structured interview
      versus the Phobia Origins Questionnaire.
AB  - Memory for fear onset events was examined in 43 dog-fearful and 48
      blood/injection-fearful participants. Half of each fear type was administered the
      Phobia Origins Questionnaire (POQ), and half the Phobia Origins Structured
      Interview (POSI). Written accounts of recalled onset experiences were sent to
      participants' parents for verification. More participants assessed by the POQ
      reported a phobia onset event (93%) than did those assessed by the POSI (54%). A
      majority in both methods recalled conditioning-like experiences. The POQ resulted
      in more reports of vicarious and informational onset reports than did the POSI.
      Parents confirmed more onset event reports obtained by the POSI (81%) than those
      obtained by the POQ, (50%). In addition, in 21% of cases where a child recalled
      an event, a parent reported an onset event that predated the one provided by the
      child. Results are discussed in terms of memory mechanisms operative in
      autobiographical memories.

PMID- 9926523
TI  - Evaluation of a multicomponent, behaviorally oriented, problem-based "summer
      school" program for adolescents with diabetes.
AB  - A 2-week summer school program, combining problem-based learning with behavior
      therapy, was developed to help adolescents with insulin-dependent diabetes
      improve their ability to cope with obstacles to dietary management. Ten students
      participated in a first session, and 9 participated in a second session, serving
      as a waiting list control group. Outcomes were evaluated pre- and postsession and
      at a 4-month follow-up using 3-day food diaries, blood glucose data, and paper
      and-pencil tests of diabetes-related knowledge, self-efficacy, coping strategies,
      and general problem solving. Improvements were observed in self-efficacy, problem
      solving skills, and self-reported coping strategies. No significant changes were
      observed in daily intake of fat, cholesterol, calories, mean blood glucose levels
      or blood glucose variability, and diabetes knowledge. Comparisons between the
      first group and the waiting list control group do not allow the significant pre
      post changes to be clearly attributed to the summer school program.

PMID- 9926524
TI  - Strategies for preparing clients for treatment. A review.
AB  - Substantial numbers of mental health clients do not return following their
      initial therapy visits or drop out of treatment prematurely. Two general classes
      of strategies designed to reduce premature attrition and enhance treatment
      participation are reviewed. Research on psychotherapy preparatory techniques
      (role induction, vicarious therapy pretraining, and experiential pretraining)
      indicates that these educational techniques are effective in reducing early
      treatment attrition and may be especially effective with populations at high risk
      for dropout (e.g., lower socioeconomic groups, chronically mentally ill clients,
      and institutionalized juvenile delinquents). Motivational interviewing, a
      technique originally developed for clients with alcohol problems, is designed to
      reduce client ambivalence toward therapy and change and enhance commitment to and
      motivation for treatment. Research in the alcohol field suggests that a session
      of pretreatment motivational interviewing enhances treatment outcome. Both
      motivational interviewing and psychotherapy preparatory techniques are relatively
      brief and easy to incorporate into existing mental health care.

PMID- 9926525
TI  - Recorded audio prompts. A strategy to increase independent prevocational task
      completion in individuals with dual diagnosis.
AB  - This research was conducted to teach two adults with schizophrenia and mental
      retardation to respond to recorded audio prompts in order to eliminate the need
      for instructor assistance in completing routine prevocational tasks. Studying
      individuals with dual diagnosis is an important step in moving toward success in
      community living and vocational placement. A multiple probe design across tasks
      was conducted. Prior to the investigation, both individuals demonstrated low
      levels of independent task completion. Following the implementation of the audio
      prompts, both individuals' task completion performances dramatically increased.
      These findings suggest that audio prompts may serve as an efficient alternative
      to instructor promoting, which is often required by individuals with dual
      diagnosis in prevocational job settings.

PMID- 9926526
TI  - Ultrarapid opiate detoxification.

PMID- 9926527
TI  - Conversation with Howard Blane.

PMID- 9926528
TI  - Bloodborne viral infection in Irish injecting drug users.
AB  - AIMS: In Dublin, harm reduction strategies have greatly expanded since 1990. We
      sought to determine the prevalence of, and factors associated with, hepatitis C
      (HCV), hepatitis B (HBV) and HIV infections among injecting drug users (IDUs)
      against this background. DESIGN: Cross-sectional survey. SETTING: Addiction
      treatment clinic. PARTICIPANTS: Seven hundred and thirty-five IDU tested for
      antibody to HCV (anti-HCV) between September 1992 and September 1997.
      MEASUREMENTS: Socio-demographic and drug use characteristics. Serology tests for
      anti-HCV, HBV surface antigen (HBsAg) and HIV. FINDINGS: The vast majority (89%)
      commenced injecting since 1990. Prevalence of anti-HCV was 61.8% (453/733), of
      HBsAg was 1.0% (7/729) and of HIV was 1.2% (7/600). Logistic regression analyses
      indicated that longer history of injecting and increased daily drug expenditure
      were the only independent variables associated with significantly increased risk
      of HCV. The only characteristic associated with increased prevalence of HBsAg was
      a history of injecting prior to 1990 (3.8%, 3/80). HIV prevalence was
      significantly higher when aged over 24 years (3.7%, 6/162), when injecting
      commenced prior to 1990 (6.3%, 4/64) and when injecting over 5 years (6.5%,
      4/62). CONCLUSIONS: HIV prevalence has sustained a low level in this population.
      Interventions which aim to halt transmission of HCV are necessary and will need
      to target IDU very early in their injecting careers and also those at risk of
      commencing to inject.

PMID- 9926529
TI  - Patterns of sexual and injecting risk behaviours in French intravenous drug users
      not reporting HIV and hepatitis C virus seropositivities.
AB  - AIMS: To characterize and identify determinants of risk behaviour patterns of
      intravenous drug users (IDUs) independently of changes due to knowledge of HIV or
      hepatitis C Virus (HCV) seropositivity. DESIGN: A cross-sectional survey using a
      structured questionnaire concerning sexual, injecting and HIV and HCV antibody
      testing practices. SETTING: IDUs were interviewed in the Paris region at 10
      treatment or psychosocial centres. PARTICIPANTS: Six hundred and twelve
      consecutive sexually active IDUs over 18 years able to answer the questionnaire.
      MEASUREMENTS: Five hundred and ninety-five IDUs completed the questionnaire. The
      risk-behaviour patterns of the 328 IDUs not reporting HIV or HCV seropositivity
      were analysed by phi correlation. Risk factors for each risk behaviour were
      determined by regression logistic models yielding odds ratios (OR) and their 95%
      confidence intervals (95% CI). FINDINGS: Several risk behaviour patterns were
      suggested: (1) lending, borrowing; (2) not or inconsistently testing HIV and HCV
      serology and not or inconsistently using condoms; (3) having multiple partners
      and prostitution; and (4) not using clean equipment. Alcohol abuse was
      independently and specifically associated with lending (OR = 3.8; 95% CI: 2.1
      7.0) and borrowing (OR = 3.3; 95% CI: 1.8-6.1); homelessness with injecting risk
      behaviours and with prostitution (OR = 2.7; 95% CI: 1.2-6.1); low educational
      level and having children with not or inconsistently using condom and serology
      testing; and cocaine use with not or inconsistently using condoms (OR = 0.4; 95%
      CI: 0.3-0.7) and serology testing and not using clean equipment (OR = 0.4; 95%
      CI: 0.2-0.8). Having multiple partners and prostitution had no common risk
      factors. CONCLUSIONS: Identifying specific risk factors could help to target drug
      harm reduction programmes for each risk behaviour pattern among IDUs not
      reporting HIV and HCV seropositivity.

PMID- 9926530
TI  - Comparison of the frequency and enjoyability of pleasant events in cocaine
      abusers vs. non-abusers using a standardized behavioral inventory.
AB  - AIMS: To examine whether cocaine abusers differ from non-abusers in their
      frequency and enjoyability of engaging in various "pleasant events", in order to
      approximate the density of positive reinforcement experienced in their natural
      environment. DESIGN: Comparisons of cocaine abusers to normative data and matched
      controls. SETTING: An outpatient substance abuse treatment center in Burlington,
      Vermont, USA. PARTICIPANTS: Subjects included 100 individuals enrolled in
      outpatient treatment for cocaine abuse or dependence and 50 community volunteers
      without histories of drug abuse or other major psychiatric illness and matched to
      cocaine-dependent patients on age, sex and SES. MEASUREMENTS: Diagnostic
      assessments were based upon clinical interviews using the DSM-III-R checklist.
      The primary focus of this study was the Pleasant Events Schedule (PES), a self
      rated behavioral inventory of the frequency and enjoyability of engaging in
      "pleasant" activities. Cocaine use history, treatment outcome and other relevant
      variables were also assessed. FINDINGS: Cocaine abusers reliably reported lower
      frequency of non-social, introverted, passive outdoor and mood-related activities
      than controls. These differences remained after controlling for demographic and
      life-style differences between groups, with the exception of mood-related
      activities. Perceived enjoyability of the activities did not differ across
      groups. Intravenous cocaine use and prior treatment for cocaine abuse predicted
      particularly low frequency of pleasant activities. Greater frequency of non
      social activities predicted better treatment outcome. CONCLUSIONS: Drug abuse is
      associated with low density of certain types of non-drug reinforcement.
      Systematic increases in these activities may improve treatment outcome.

PMID- 9926531
TI  - Choosing a diagnostic cut-off for cannabis dependence.
AB  - AIM: While cannabis dependence has been increasingly recognized, there is little
      research on the measurement issues involved in operationalizing the dependence
      syndrome for this drug. This paper aimed to investigate the diagnostic utility
      and appropriate diagnostic cut-offs of three short dependence measures among long
      term cannabis users. SETTING AND PARTICIPANTS: Two hundred long-term, regular
      cannabis users were recruited and interviewed in Sydney, Australia. MEASUREMENTS:
      Receiver Operating Characteristic analyses compared the diagnostic performance of
      the short University of Michigan CIDI, a measure of ICD-10 dependence and the
      Severity of Dependence Scale against the "gold standard" of moderate or more
      severe DSM-III-R cannabis dependence, as diagnosed by the Substance Abuse Module
      of the CIDI. FINDINGS: The measures were of equal utility in diagnosing at least
      moderate DSM-III-R cannabis dependence. While the optimal diagnostic cut-offs for
      the short University of Michigan CIDI and the ICD-10 dependence measure remained
      unchanged from those conventionally applied, a more liberal cut-off was optimal
      for the Severity of Dependence Scale. The amended prevalence of cannabis
      dependence was 77% using the short University of Michigan CIDI, 72% by the ICD-10
      measure and 62% by the Severity of Dependence Scale. CONCLUSIONS: The three
      instruments were able to diagnose cannabis dependence at levels substantially
      better than chance. They were generally robust in terms of the optimal diagnostic
      cut-off in a population of long-term cannabis users. This paper provides
      guidelines for choosing optimal cut-offs within different contexts.

PMID- 9926532
TI  - Factors associated with marijuana use among American Indian adolescents.
AB  - AIM: To examine the characteristics of marijuana users among a large sample of
      American Indian high school students. DESIGN: High school survey. SETTING: Seven
      predominantly American Indian high schools in four communities west of the
      Mississippi. PARTICIPANTS: 1464 Indian adolescents who: (1) completed a survey in
      November, 1993, (2) were in grades 9 to 12, (3) were members of one of four
      Indian tribal groups; and (4) had a complete set of data for these analyses.
      MEASUREMENTS: Logistic regression models were developed to predict the
      probability of low-frequency (1-3 times over the last month) and high-frequency
      (11 or more times) marijuana use. Independent variables included measures of
      socio-demographics, stressful life events, personal characteristics and beliefs,
      psychiatric symptomatology and other substance use. FINDINGS: Forty per cent of
      these American Indian adolescents had used marijuana at least once in the last
      month. The prevalence of marijuana use varied across the four tribes. Males were
      no more likely than females to use marijuana at a low frequency, but were more
      likely to use at a high frequency. The factors associated with marijuana use
      varied with the frequency of use and by gender. In the final multivariate models,
      low-frequency marijuana use among females was associated with reporting that
      peers encouraged alcohol use as well as use of alcohol and stimulants. Among
      males, low-frequency use was associated with greater positive alcohol
      expectancies, lower grades in school and alcohol use. While high-frequency
      marijuana use was associated with use of alcohol, stimulants and cocaine among
      females, such use was associated with higher scores on the antisocial behavior
      scale as well as the use of alcohol, stimulants and cocaine among males. Overall,
      the strongest associations were with the use of alcohol and other illicit
      substances. CONCLUSION: Low-frequency and high-frequency marijuana use are
      distinct patterns of use and have different correlates across genders. Marijuana
      use among American Indian adolescents is a complex phenomenon that is best
      understood within the context of other substance use.

PMID- 9926533
TI  - A social marketing model for disseminating research-based treatments to
      addictions treatment providers.
AB  - AIMS: Researchers must develop effective strategies for disseminating research
      based treatments. This study evaluates the application of a dissemination model
      based on principles of social marketing and diffusion theory. DESIGN: A case
      study describes how the model was implemented. A qualitative design was employed
      to examine rates of adoption and adaptation of an early intervention program by a
      targeted system of addictions agencies. SETTING: The interventions were developed
      at the Addiction Research Foundation in Toronto and disseminated to Assessment
      and Referral (A/R) Centres in Ontario, Canada. PARTICIPANTS: Study participants
      included the managers and a designated therapist for 33 participating A/R
      centres. MEASUREMENTS: Managers were asked mainly open-ended questions concerning
      whether their agency had made a formal decision to adopt the intervention and
      whether therapists in their agency were using the early intervention program.
      "Adoption" was operationalized as offering the complete four-session intervention
      to at least one client. FINDINGS: At 12 months after the completion of training
      workshops, 68% of 34 agencies in the target system had adopted the program while
      85% of the agencies were using some components of the intervention with clients.
      CONCLUSIONS: The dissemination model appeared to be effective although its
      application proved to be time-consuming and labour-intensive. The "market
      analysis", systems focus and field-test components of the model appeared to
      contribute to its success.

PMID- 9926534
TI  - Changes in social roles as predictors of changes in drinking behaviour.
AB  - AIM: To assess the possible effects of changes in marital status, employment
      status and having children at home on alcohol consumption and the frequency of
      heavy drinking. With role theory as a starting point it was expected that a shift
      into more social roles would decrease consumption and heavy drinking while the
      shift away from social roles would be associated with an increase in consumption
      and heavy drinking. DESIGN: Prospective cohort study. SETTING: The province of
      Limburg, The Netherlands (1980-89). PARTICIPANTS: 1327 men and women aged 16-69
      years at first measurement. MEASUREMENTS: Weekly consumption of standard units
      (10 g ethanol) of alcoholic beverages; frequency of drinking six units or more;
      self-reported social role. FINDINGS: The acquisition of a spouse role and a
      parental role but not an employment role was associated with a decrease in
      consumption or heavy drinking. The loss of the spouse role among women was
      associated with an increase in heavy drinking. Otherwise, losing a role was not
      linked with a change in consumption and heavy drinking. CONCLUSIONS: Limited
      support was found for the expectation that role transitions influence drinking
      behaviour. Our study suggests that other theories must be sought to explain
      social differences in drinking behaviour.

PMID- 9926535
TI  - How healthy are the police? A survey of life-style factors.
AB  - AIMS: To examine the prevalence of five life-style behaviours among New South
      Wales police. DESIGN: A cross-sectional survey using a self-administered
      questionnaire. SETTING AND PARTICIPANTS: A total of 852 police were recruited
      from metropolitan Sydney. MEASUREMENTS: Prevalence related to age and sex of self
      reported alcohol consumption, cigarette smoking, inadequate exercise, perception
      of overweight and stress symptoms. RESULTS: A high level (89%) of participation
      was achieved in the survey. Almost half (48%) of males and more than two-fifths
      (40%) of females consumed alcohol excessively including continuous hazardous or
      harmful consumption and binge drinking. Excessive drinking was more prevalent
      among younger police. There were 8% of male and 15% of female police who reported
      that they did not drink alcohol. Over one-quarter (27%) of male and one-third
      (32%) of female respondents reported smoking. Almost half (46%) of men and women
      (47%) believed that they were overweight. More than one-fifth (21%) of men and
      less than one-quarter (24%) of women reported that they did not exercise.
      Finally, 12% of men and 15% of women reported feeling moderate to severe symptoms
      of stress. CONCLUSIONS: The police work-force offers an opportunity to screen for
      a large number of healthy, young and high risk individuals (particularly men) who
      are hard to reach in other settings and who rarely visit their general
      practitioner. A sizeable majority (83%) of NSW police had at least one unhealthy
      life-style behaviour with 19% reporting 3-5 unhealthy factors. The high
      prevalence of excessive alcohol consumption among police is of particular
      concern. More active health promotion and provision of brief interventions among
      police may reduce morbidity and mortality associated with unhealthy life-styles.

PMID- 9926536
TI  - Mediterranean mysteries: mechanisms of declining alcohol consumption.

PMID- 9926537
TI  - Images and realities of alcohol.
AB  - The paper discusses the relationship between the images of alcohol and society,
      on one hand, and the reality of drinking and drinking problems on the other hand,
      from the point of view of policy-relevant research. Images of alcohol influence
      policy but they also depend on the social and cultural environment of policy
      making. The epidemiological total consumption theory of alcohol-related problems
      is used as an example. The theory is embedded in the modern welfare state's
      ideals and its policy relevance presupposes that these ideals--universalism,
      consequentialism and public planning--are respected. If the approach today
      receives less attention by policy-makers than its empirical validity merits, it
      may be due to an erosion of these ideals, not of the epidemiological model
      itself. Images of alcohol influence behaviour and drinking problems but they also
      articulate the social context in which the images are constructed. This paper
      demonstrates the point, applying Levi-Straussian cultural theory to an analysis
      of a recent beer advertisement addressed to young people. The advertisement not
      only reflects the images associated with youthful drinking but also the ambiguous
      status of youth as non-adults in contemporary society. The author stresses that
      for social and cultural research alcohol is a two-way window, to look at society
      through alcohol and to look at alcohol through society. Both directions are
      necessary for policy-relevant research.

PMID- 9926538
TI  - Network support for drinking, Alcoholics Anonymous and long-term matching
      effects.
AB  - AIMS: (1) To examine the matching hypothesis that Twelve Step Facilitation
      Therapy (TSF) is more effective than Motivational Enhancement Therapy (MET) for
      alcohol-dependent clients with networks highly supportive of drinking 3 years
      following treatment; (2) to test a causal chain providing the rationale for this
      effect. DESIGN: Outpatients were re-interviewed 3 years following treatment.
      ANCOVAs tested the matching hypothesis. SETTING: Outpatients from five clinical
      research units distributed across the United States. PARTICIPANTS: Eight hundred
      and six alcohol-dependent clients. INTERVENTION: Clients were randomly assigned
      to one of three 12-week, manually-guided, individual treatments: TSF, MET or
      Cognitive Behavioral Coping Skills Therapy (CBT). MEASUREMENTS: Network support
      for drinking prior to treatment, Alcoholics Anonymous (AA) involvement during and
      following treatment, percentage of days abstinent and drinks per drinking day
      during months 37-39. FINDINGS: (1) The a priori matching hypothesis that TSF is
      more effective than MET for clients with networks supportive of drinking was
      supported at the 3 year follow-up; (2) AA involvement was a partial mediator of
      this effect; clients with networks supportive of drinking assigned to TSF were
      more likely to be involved in AA; AA involvement was associated with better 3
      year drinking outcomes for such clients. CONCLUSIONS: (1) In the long-term TSF
      may be the treatment of choice for alcohol-dependent clients with networks
      supportive of drinking; (2) involvement in AA should be given special
      consideration for clients with networks supportive of drinking, irrespective of
      the therapy they will receive.

PMID- 9926539
TI  - Alcohol and all-cause mortality in Europe 1982-1990: a pooled cross-section time
      series analysis.
AB  - AIM: To test the relationship between alcohol consumption and all-cause
      mortality. DESIGN:  DATA: Yearly mortality rates and per capita consumption from
      25 European countries between 1982 and 1990. STATISTICAL MODELS: This paper
      employs time-series cross-sectional data to model the relationships between
      alcohol consumption and all-cause mortality. The data are derived from 25
      European countries in the 1980s. The statistical analyses controlling cross
      sectional correlation and timewise autoregression were used to implement the
      econometric modelling. FINDINGS: Increases (decreases) in the per capita
      consumption of 1 litre of pure alcohol were associated with increases (decreases)
      of 1.3% in all-cause mortality rates. The beverage-specific analyses indicated a
      significant relationship between consumption of beer and all-cause mortality
      only. CONCLUSION: The data show that per capita alcohol consumption, according to
      reported levels in Europe, is related to all-cause mortality and is thus of
      relevance to public health.

PMID- 9926540
TI  - Use of alcohol to cope with tension, and its relation to gender, years in medical
      school and hazardous drinking: a study of two nation-wide Norwegian samples of
      medical students.
AB  - AIMS: To study the association between the use of alcohol to cope with tension
      and hazardous drinking, and the prevalence and the predictors of such drinking
      behaviours. DESIGN: Cross-sectional surveys of two nation-wide samples of medical
      students, one at the beginning and one at the end of medical training.
      PARTICIPANTS: Medical students entering Norwegian medical schools in 1993 (N =
      379) or graduating in 1993 and 1994 (N = 522); 55.6% of the total sample were
      women. MEASUREMENTS: Postal questionnaires including SCL-5, Perceived Medical
      School Stress. FINDINGS: Use of alcohol to cope was reported by 10.5% of the
      students with no significant gender difference. Hazardous drinking ('binge
      drinking' at least 2-3 times per month) was reported by 14% of all the students,
      24% among the men and 6% among the women. There was a strong association between
      use of alcohol to cope with tension and hazardous drinking, OR = 5.11, 95% CI
      (2.88-9.07) when controlling for other possible predictors. Use of alcohol to
      cope was also associated with increasing age, mental distress and lack of
      religious activity. The senior students used alcohol as a way of coping less
      often, but not hazardous drinking. Male gender, religious inactivity, high self
      esteem and having no children were predictors of hazardous drinking. CONCLUSION:
      This study suggests that the use of alcohol to cope with tension is an
      independent risk factor connected with hazardous drinking among medical students,
      with no difference in prevalence between the genders.

PMID- 9926541
TI  - Parental substance use disorder, mediating variables and adolescent drug use: a
      non-recursive model.
AB  - AIMS: To develop and test a non-recursive model that examines the effects of
      parental psychoactive substance use disorder (PSUD) on the reciprocal
      relationships among stressful life events, family attachment, peer drug use and
      adolescent drug use. DESIGN: A 3-year prospective cohort study followed
      adolescents from three types of families defined by a parental diagnosis of a
      psychiatric disorder. SETTING: A large metropolitan area in the upper Midwestern
      United States. PARTICIPANTS: Seven hundred and seventy-seven 10-16-year-old
      adolescents from three groups of families: 214 who resided in families in which a
      parent was diagnosed with PSUD, 181 who resided in families in which a parent was
      diagnosed with an affective disorder (but no co-morbid PSUD), and 382 who resided
      in families in which both parents were free of any diagnosable disorder.
      MEASUREMENTS: Psychiatric disorder was defined by the Structured Clinical
      Interview for DSM-III-R (SCID). Two follow-up interviews of adolescent
      respondents were used to measure stressful life events via the Junior High Life
      Experiences Survey, family attachment via FACES-III and a child-parent strain
      index, peer drug use, and two self-reported drug use scales designed to measure
      past-year alcohol use and illicit drug use (e.g. marijuana, cocaine, inhalants).
      FINDINGS: Nested structural equation models with latent variables revealed that
      adolescents from PSUD families were at heightened risk of stressful life events,
      peer drug use, attenuated family attachments and drug use during the first follow
      up period. In turn, peer drug use was strongly associated with drug use during
      the second follow-up period. However, drug use during the first follow-up also
      led to greater peer drug use and attenuated family attachment during the second
      follow-up period. The findings support a non-recursive model describing relations
      among adolescent drug use, peer drug use and family attachment. CONCLUSIONS:
      Parental psychoactive substance use disorder puts adolescents at significant risk
      of becoming embedded in a cycle of drug use, associations with drug using peers,
      and poor family relations.

PMID- 9926542
TI  - Sexual abuse and alcoholism in a female population.
AB  - AIMS: (1) To study the prevalence of childhood sexual abuse before the age of 18
      years (CSA) and life-time sexual abuse (LSA) in a Swedish female, general
      population, (2) to analyse associations between CSA and life-time alcohol
      dependence or abuse (ADA), and (3) to identify possible confounding factors.
      DESIGN AND PARTICIPANTS: The study was conducted in two phases. Phase 1: an
      alcohol problem screening questionnaire was sent to 3130 women aged 25-65. The
      answers were scored. Phase 2: based on the questionnaire scores, a randomly
      selected stratified sample of 479 women was invited for an interview. Of these,
      316 women participated in a structured face-to-face interview. SETTING: A sector
      of Goteborg city with 100,000 inhabitants. MEASUREMENTS: The interviews focused
      on substance use and on social, psychological and behavioural characteristics,
      including experiences of sexual abuse. Clinical psychiatric diagnoses were made
      according to DSM-III-R. Bivariate analyses and multivariate logistic regression
      analyses were performed. FINDINGS: The prevalence of CSA and LSA was 9.8% and
      13.9%, respectively. CSA increased the risk for life-time ADA and anxiety, but
      not for depression. When potential confounding factors (e.g. early background
      factors, depression and anxiety) were adjusted for, CSA under 13 years of age
      still predicted ADA in multivariate analyses, but CSA under 18 years of age did
      not. CONCLUSIONS: LSA, and especially CSA under 13 years of age, are factors that
      should be considered in treatment of women with ADA and in psychiatric treatment
      of women.

PMID- 9926543
TI  - Familial influences on gambling behavior: an analysis of 3359 twin pairs.
AB  - BACKGROUND: Pathological gambling is becoming an increasing problem in the United
      States as the number of legalized gambling establishments grows. To examine
      vulnerability to pathological gambling, we estimated the familial contributions
      (i.e. inherited factors and/or experiences shared by twin siblings during
      childhood) to DSM-III-R pathological gambling symptoms and disorder. METHODS:
      Data were obtained from a telephone interview performed in 1991-92 utilizing the
      Diagnostic Interview Schedule Version III-Revised. Interviews were administered
      to 6718 members of the nationally distributed Vietnam Era Twin Registry of male
      male monozygotic and dizygotic twin pairs who served in the military during the
      Vietnam era. RESULTS: Inherited factors explain between 35% (95% CI: 28%, 42%)
      and 54% (95% CI: 39%, 67%) of the liability for the five individual symptoms of
      pathological gambling behavior that could be estimated statistically. In
      addition, familial factors explain 56% (95% CI: 36%, 71%) of the report of three
      or more symptoms of pathological gambling and 62% (95% CI: 40%, 79%) of the
      diagnosis of pathological gambling disorder (four or more symptoms). CONCLUSIONS:
      Familial factors have an important influence on risk for pathological gambling
      behavior. The increasing access to legalized gambling is likely to result in a
      higher prevalence of pathological gambling behavior among individuals who are
      more vulnerable because of familial factors.

PMID- 9926544
TI  - Six deaths linked to concomitant use of buprenorphine and benzodiazepines.
AB  - AIMS: Buprenorphine at high dosage became available in 1996 for substitution
      treatment in France. This drug is considered particularly safe and has become
      widely available in general medical practice. We investigated the possible
      implication of a buprenorphine-benzodiazepine association in six deaths of known
      abusers. DESIGN: Full investigation of cause of death was conducted for six drug
      abusers. SETTING: The deaths occurred in two regions of France (Auvergne and
      Lorraine). Assays were carried out by the Institut de Medecine Legale at
      Strasbourg, France, one of the few French laboratories equipped to assay
      buprenorphine. MEASUREMENT: First, the blood and urine underwent triple
      exhaustive screening. Secondly, buprenorphine and norbuprenorphine were analysed
      in all the autopsy samples by HPLC/MS. FINDINGS: Benzodiazepine-buprenorphine
      associations were found in every case; no other substances that could account for
      the death were found. The tissue concentrations were markedly higher than the
      blood levels. CONCLUSION: If the number of deaths linked to such drug misuse
      proves high, it may be necessary to review how buprenorphine is dispensed.

PMID- 9926545
TI  - Risk factors for and knowledge of Mycobacterium tuberculosis infection among drug
      users in substance abuse treatment.
AB  - OBJECTIVE: To determine the prevalence, incidence and risk factors for
      Mycobacterium tuberculosis infection, as well as to assess TB knowledge and
      attitudes, among a group of known drug users in a city with low TB incidence
      (11.3 per 100,000 in 1995). METHODS: Patients of an urban drug treatment facility
      enrolled in opioid substitution, opioid antagonist and other drug treatment
      programs were screened for TB, including tuberculin skin testing and standardized
      data collection on TB risk factors. A subsample of clients was interviewed about
      TB knowledge and attitudes. RESULTS: Between 1 June 1995 and 31 May 1996, 1055
      individuals were screened. The prevalence of infection was 15.7% (CI: 13.2
      18.2%). PPD positivity was associated with older age (per annum, OR = 1.08, CI:
      1.05-1.11), non-white race (OR = 2.81, CI: 1.72-4.60), foreign birth (OR = 4.24,
      CI: 2.35-7.62) and a history of injecting drug use (OR = 1.89, CI: 1.14, 3.12).
      The incidence of infection was 2.9 per 100 person-years (CI: 1.8-4.7). Thirty-two
      per cent of 79 drug users interviewed about TB knowledge and attitudes thought TB
      could be prevented by bleaching or not sharing needles/syringes. Fifty-one per
      cent thought anyone with a positive TB skin test was contagious. CONCLUSION: M.
      tuberculosis infection was common in this population and associated with
      injecting drugs and several demographic factors. The incidence of new infection
      was relatively low. In this non-endemic environment, the detection and treatment
      of latent infection are important aspects of TB control. Misconceptions about TB
      transmission were also widespread in this population. Drug treatment programs can
      play a key role by undertaking screening programs that educate about TB and
      identify infected subjects who would benefit from preventive therapy.

PMID- 9926547
TI  - High rates of drug use, but low rates of HIV risk behaviours among injecting drug
      users during incarceration in Dutch prisons.
AB  - AIMS: To determine levels of injecting drug use and sexual risk behaviours in
      injecting drug users during and immediately following imprisonment in The
      Netherlands. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional survey of drug
      injectors attending methadone clinics, a sexually transmitted disease clinic and
      a central research site in Amsterdam. The mean age of the 188 participants was 35
      years, 78% were male and 34% had HIV antibodies. MEASUREMENTS: Self-reported drug
      use and sexual behaviours during the last period of imprisonment in Dutch prisons
      within the previous 3 years and injecting drug use in the week following release
      from prison. FINDINGS: A period of imprisonment in the preceding 3 years was
      reported by 188 (41%) of 463 interviewed drug injectors. The mean duration of
      last imprisonment was 3.6 months. Any use of cannabis, heroin or cocaine during
      imprisonment was reported by 55%, 37% and 20%, respectively. Five injectors (3%)
      admitted to having injected in prison, but no sharing of needles and syringes was
      reported. Vaginal or anal sex was reported by two (1%) of the men and none of the
      women. Relapse to drug injecting during the week following release from prison
      was reported by 78/186 (42%) participants, in most cases (34%) at the very first
      day of release. Drug use behaviours during imprisonment were similar for those
      who were designated current injectors at the time of imprisonment and those who
      were not, but injecting in the first week following release from prison was far
      higher among 'current' injectors (63%) than among those who were not (11%).
      CONCLUSIONS: Contrary to findings from other countries, low levels of HIV risk
      behaviours occur among imprisoned drug injectors in The Netherlands. Intra-prison
      HIV preventive measures should be considered taking into account the nationally,
      regionally or locally varying conditions within the existing prisons.

PMID- 9926546
TI  - Drug scene roles and HIV risk.
AB  - AIMS: Drug scenes (social and spatial drug-using and drug-selling environments)
      have complex role structures. Many drug injectors earn money or drugs as drug or
      syringe sellers, hit doctors (people who help others to inject) commercial sex
      workers, or in other roles. This paper aims to measure "role behaviors" of drug
      injectors; describe which drug injectors are more likely to engage in such role
      behaviors; and to determine whether roles are related to elements of HIV risk.
      DESIGN: Cross-sectional study of drug injectors. SETTING: Bushwick, a section of
      Brooklyn, New York, a major location for injection drug use and drug sales.
      PARTICIPANTS: Seven hundred and sixty-seven street-recruited drug injectors.
      MEASUREMENTS: Participants were interviewed about their roles, behaviors, socio
      demographics and risk networks; sera were collected and assayed for HIV and
      hepatitis B core antibody. FINDINGS: Socio-demographic variables are related to
      role-holding in complex ways. Economic need is generally associated with engaging
      in drug-scene role behaviors. Holders of these roles are at greater behavioral
      and network risk for HIV and other blood-borne infections than are other drug
      injectors. They also engage in extensive communication with other drug users,
      including discussion of HIV risk reduction. CONCLUSION: Role behaviors can be
      measured in quantitative studies, and seem to be related to HIV risk. Role
      holders may be strategic targets for risk-reduction campaigns. It seems feasible
      and advisable to measure drug scene role-holding in research on drug users.

PMID- 9926548
TI  - Nicotine absorption and dependence in unlicensed lozenges available over the
      counter.
AB  - AIM: To demonstrate the nicotine absorption and dependence potential from
      unlicensed nicotine containing lozenges. DESIGN: A single case report of
      dependence on nicotine lozenges, plus measurements of nicotine levels before and
      after consumption of eight nicotine lozenges over 2 hours in volunteers. SETTING:
      Hospital Smokers' Clinic. PARTICIPANTS: One male patient suffering from
      schizophrenia who had consumed 150 "Stoppers" lozenges per day for the previous 5
      years, plus seven non-smoker volunteers. MEASUREMENTS: Blood nicotine
      concentration. FINDINGS: The patient's low expired carbon monoxide level (5
      p.p.m.) and high plasma nicotine (32 ng/ml) and cotinine levels (947 ng/ml) were
      consistent with very heavy lozenge consumption. The non-smoker volunteers
      obtained nicotine concentrations of around 11 ng/ml by consuming eight Stoppers
      lozenges over 2 hours. Other brands of nicotine lozenges produced lower initial
      levels, but also produced delayed intestinal absorption and vomiting after food
      consumption. CONCLUSION: Nicotine lozenges are a potential aid to smoking
      cessation but their safety, efficacy and abuse potential remain to be properly
      evaluated.

PMID- 9926549
TI  - Maternal use of heroin and methadone and infant birth weight.

PMID- 9926550
TI  - The respiratory risks of cannabis smoking.

PMID- 9926551
TI  - Science and alcohol policy at the local level: a respectful partnership.
AB  - This paper describes the working exchange between scientists who designed a three
      community prevention trial in the United States (1990-95) to reduce alcohol
      involved injuries at the community level, and community organizers and local
      policy-makers in the experimental sites. We found that researchers brought
      scientific knowledge of potentially effective alcohol policies but had no
      experience with the local culture, priorities or processes; conversely, community
      organizers understood the local situation but were not knowledgeable about
      prevention strategies which, based on prior evidence, could work. We also found
      that communities are interested in science to aid the selection of local alcohol
      policies, but scientists do not understand local dynamics well enough to direct
      the implementation of these policies. This case study showed that both groups
      must respect each other and seek ways to work together for the mutually desired
      outcome of effective local prevention.

PMID- 9926552
TI  - Educating young people about drugs: a systematic review.
AB  - AIMS: To assess the effectiveness of interventions directed at the prevention or
      reduction of use of illicit substances by young people or those directed at
      reducing harm caused by continuing use. DESIGN: A systematic review was
      conducted. Reports were identified through electronic and hand searching and
      contact with known workers in the area. Studies were included if they reported
      evaluations of interventions targeting illicit drug use and provided sufficient
      detail of the intervention and design of the evaluation to allow judgements to be
      made of their methodological soundness. Meta-analyses were conducted combining
      the data of the methodologically sound studies. PARTICIPANTS AND SETTINGS
      TARGETED BY INTERVENTIONS: Evaluations of interventions were included if their
      targeted audience included young people aged between 8 and 25 years. Identified
      evaluations were delivered in a range of settings including: schools and
      colleges; community settings; the family; medical/therapeutic settings; mass
      media. MEASUREMENTS: Data extracted from each report included details of design,
      content and theoretical orientation of intervention, setting of the intervention,
      target audience, methods, population size, subject refusal rates, rates of
      attrition, outcome measures, length of follow-up and findings, including
      statistical power. FINDINGS: The majority of studies identified were evaluations
      of interventions introduced in schools and targeting alcohol, tobacco and
      marijuana simultaneously. These studies were methodologically stronger than
      interventions targeting other drugs and implemented outside schools. Meta
      analyses showed that the impact of evaluated interventions was small with
      dissipation of programme gains over time. Interventions targeting hard to reach
      groups have not been evaluated adequately. CONCLUSIONS: Effort needs to be
      directed towards the development of improved evaluative solutions to the problems
      posed by these groups. There is still insufficient evidence to assess the
      effectiveness of the range of approaches to drugs education; more
      methodologically sound evaluations are required. There is also a need to target
      interventions to reflect the specific needs and experiences of recipients.

PMID- 9926553
TI  - Supplemental social services improve outcomes in public addiction treatment.
AB  - AIMS: To evaluate the effectiveness and value of social services added to
      standard addiction rehabilitation. DESIGN: A controlled, quasi-experimental,
      field study with repeated measures. SETTING: Conducted in two groups of publicly
      supported outpatient addiction treatment programs. Control programs provided
      standard, twice-weekly, outpatient group counseling. "Enhanced" programs provided
      standard counseling but also case managers to coordinate and expedite use of pre
      contracted medical screenings, housing assistance, parenting classes and
      employment services. MEASUREMENTS: The Addiction Severity Index was used to
      record the nature and severity of patient problems in seven areas at treatment
      admission and at 6-month follow-up. Services provided during treatment were
      measured with the Treatment Services Review. Measures were taken on consecutive
      samples of patients admitted to all programs--before enhancements (wave 1, N =
      431)--and at 12 months (wave 2, N = 710); and 26 months following enhancements
      (wave 3, N = 187). FINDINGS: There were no significant differences in patient
      characteristics, treatment services or 6-month outcomes of the two sets of
      programs in wave 1. Wave 2 and especially wave 3 enhanced programs provided
      significantly more social and medical services than control programs. Patients
      treated in enhanced programs showed significantly less substance use, fewer
      physical and mental health problems and better social function at 6-months than
      Controls. CONCLUSIONS: Adding social services to public sector programs
      substantially improved the outcomes of addiction treatment. Changes in "real
      world" systems require time to implement; early evaluations may fail to capture
      the full impact of those changes.

PMID- 9926554
TI  - Alcohol-related harm and alcohol consumption in Moscow before, during and after a
      major anti-alcohol campaign.
AB  - AIMS: To examine the rates of alcohol-related harm in relation to levels of
      alcohol consumption before, during and after a major anti-alcohol campaign in
      Moscow. DESIGN: Changes in State alcohol sale and alcohol consumption and certain
      forms of alcohol-related harm were observed as a function of time. FINDINGS:
      Following the 1985 anti-alcohol campaign, State alcohol sales decreased by 38.0%
      in 1.5 years in Moscow, and total consumption decreased by 28.6%. At the same
      time, admissions for alcohol-related mental and behavioural disorders, deaths
      from liver cirrhosis, alcohol poisoning and other blood alcohol positive violent
      deaths decreased by 63.3%, 33.0%, 50.8% and 50.9%, respectively. There was a
      linear correlation between medical variables and alcohol consumption during its
      decrease in 1985-86. An increase in blood alcohol positive violent deaths began
      in 1987, before the increases in other variables. Growth of total alcohol
      consumption began in 1987, and continued during all subsequent years, although it
      was especially high in 1992-93 at the time of the introduction of market reforms
      in Russia. Alcohol-related mental and behavioural disorders and liver cirrhosis
      mortality increased after a time-lag following the rise in alcohol consumption.
      CONCLUSIONS: The findings provide stark evidence of the potential impact of
      policy measures applied to general alcohol consumption on alcohol-related harm.

PMID- 9926555
TI  - Evaluating measures of family history of alcoholism: density versus dichotomy.
AB  - AIMS: Studies have used myriad measures of family history of alcoholism (FH)
      making it difficult to compare them directly. Commonly used FH measures partition
      samples into the well known positive (FH+) and negative (FH-) dichotomy, although
      quantitative measures of density potentially provide more information. A standard
      FH measure would facilitate between-study comparisons. The purpose of this study
      is to evaluate a quantitative FH measure, called Family History Density (FHD),
      that has theoretical and practical advantages over currently used measures.
      DESIGN: Logistic regression equations were estimated for FHD and six commonly
      used FH measures on alcohol dependence diagnosis, and two measures of alcoholism
      severity (i.e. withdrawal and tolerance). PARTICIPANTS: Subjects recruited for
      studies (254 men and 97 women) completed a structured clinical assessment.
      MEASUREMENTS: Alcoholism diagnosis and endorsement of tolerance or withdrawal
      symptoms were obtained using the alcohol module from the NIMH Diagnostic
      Interview Schedule III-R (DIS III-R). Family history of alcoholism was coded
      using the criteria from the Family Informant Schedule and Criteria (FISC).
      FINDINGS: All FH measures were associated with alcohol dependence diagnosis,
      development of tolerance and experiencing withdrawal symptoms in men. In women,
      only FHD and Parent were significantly associated with all three outcomes.
      CONCLUSIONS: FHD is a good candidate to be a standard FH measure because it is
      quantitative, based on familial relatedness and capable of accounting for
      significant variation in alcoholism diagnosis and two indices of alcoholism
      severity in men and in women.

PMID- 9926556
TI  - The assessment of young children's expectancies of alcohol versus a control
      substance.
AB  - AIMS: The chief purpose of the current study was to assess whether young children
      endorse expectancies specific to alcohol. DESIGN: In order to accomplish this
      aim, a 2 (gender of child) by 2 (gender of adult drinker) by 2 (grade level) by 2
      (beverage type) repeated measure design was employed with beverage type as the
      repeated measure. SETTING: Data were collected within elementary schools located
      in two Midwestern states. PARTICIPANTS: One hundred and twenty-four second and
      third graders (42% male) participated in individually structured interviews.
      MEASUREMENTS: The expectancy interview was based on the Children's Alcohol
      Related Expectancy Questionnaire and assessed each child's beliefs about the
      desirable and undesirable consequences which adult men and women might experience
      after drinking alcohol (beer) and a control beverage (iced tea). FINDINGS: The
      results indicated that children endorsed significantly more undesirable
      expectancies for beer than for iced tea, and more desirable expectancies for iced
      tea than for beer. In addition, children's expectancies varied as a function of
      the gender of the drinker. Specifically, both second- and third-graders expected
      more undesirable outcomes for women than for men, and second graders expected
      fewer desirable outcomes for women than for men, regardless of beverage.
      CONCLUSIONS: Prior to substantial experience with alcohol consumption, children
      have already developed expectancies for alcohol. Specifically, young elementary
      children endorse predominantly undesirable expectancies for beer.

PMID- 9926557
TI  - Estimating changes in unrecorded alcohol consumption in Norway using indicators
      of harm.
AB  - AIM: To assess the value of using indicators of alcohol-related harm to estimate
      changes in unrecorded per capita consumption of alcohol. DESIGN: Unrecorded
      consumption was estimated from the discrepancy between the observed changes in a
      number of alcohol-related harm indicators and the changes that would be expected
      from changes in recorded consumption. The results were compared with estimates of
      unrecorded consumption from survey data. MEASUREMENTS: Four indicators of alcohol
      related harm were used: alcohol-related mortality, assaults, drunken driving, and
      suicide. Estimates of unrecorded consumption from survey data for five different
      years were used as benchmarks. FINDINGS: The best performing indicators were
      alcohol-related mortality, suicide and assaults, in that order. Combining these
      indicators yielded a prediction error averaging 12% in comparison with the
      benchmarks. CONCLUSIONS: The method seems worthy of further applications, but it
      should be regarded as a supplement rather than as a substitute for other
      approaches.

PMID- 9926558
TI  - Alcohol-related words are distracting to both alcohol abusers and non-abusers in
      the Stroop colour-naming task.
AB  - AIM: To compare alcohol abusers' and non-abusers' distraction for alcohol-related
      and emotional words, controlling for emotional valence of those words. DESIGN AND
      METHOD: The experiment compared 20 alcohol abusers and 20 non-abusers in terms of
      performance on a computerized Stroop colour-naming test using alcohol-related and
      non-alcohol-related words. FINDINGS: Abusers rated the alcohol stimuli greater in
      emotional valence than the emotional stimuli. Therefore, differences in emotional
      valence ratings between the two groups were statistically controlled. Against
      expectation, both alcohol abusers and non-abusers were more distracted by alcohol
      stimuli than by positive or negative emotional stimuli. CONCLUSIONS: The results
      indicate that alcohol words are distracting for drinkers in general, and this may
      indicate a high level of salience for these kinds of stimuli.

PMID- 9926559
TI  - Alcohol intake and severity of injuries on highways in Mexico: a comparative
      analysis.
AB  - AIMS: To analyze the association between alcohol intake and the severity of
      injuries sustained from traffic accidents on a Mexican highway. DESIGN: An
      observational unit evaluated drivers involved in auto accidents. SETTING: Mexico
      Cuernavaca Highway, Mexico. A 60 km-long road with many altitude variations and
      sharp curves. PARTICIPANTS: Three hundred and eighty-six drivers involved in
      traffic accidents between March and September, 1994. MEASUREMENTS: A
      questionnaire was applied to the driver, an occupant or witness at the site of
      the accident to collect information about the driver, vehicle characteristics,
      type of accident, day-night occurrence, road section (Mexico-Cuernavaca or
      Cuernavaca-Mexico) and weather conditions. A physical examination was carried out
      to determine the presence and severity of injuries. FINDINGS: There were 177
      injured people, including 12 deaths, with rates of 67.5 injuries and 4.58 deaths
      per 10,000 km driven. Variables associated with alcohol intake (p < 0.05)
      included: severity of injuries, non-use of seat belt, vehicle size and occurrence
      at night. Risk factors for severe injuries were: alcohol intake (adjusted OR 6.1
      CI 95% 1.6-24.0); non-use of seat belt (OR 4.9 CI 2.2-10.8), age < 25 years (OR
      3.6 CI 1.0-12.7), age > 54 years (OR 6.0 CI 1.4-25.0), speed > 90 km/h (OR 2.6 CI
      1.1-6.3) and occurrence at night (OR 2.6 CI 1.3-5.3). CONCLUSIONS: Alcohol intake
      is a major risk factor for severe injuries from highway traffic accidents. Its
      association with other risk factors such as non-use of seat belt and excessive
      speed suggests the importance of designing interventions aimed at reducing
      alcohol intake among automobile drivers.

PMID- 9926560
TI  - Assessing the relationship between maternal opiate use and antepartum
      haemorrhage.
AB  - AIMS/DESIGN: Assessment of the association between the regular use of opiates by
      women during pregnancy and antepartum haemorrhage has been made difficult by the
      low prevalence of these conditions observed in clinical settings. As a
      consequence, most published studies lack statistical power due to the small
      number of cases. We combined all suitable published data in a meta-analysis to
      assess the association more accurately. FINDINGS: Meta-analysis produced a pooled
      estimate of the crude odds ratio for antepartum haemorrhage in relation to
      maternal opiate use of 2.33 (95% CI 1.32-4.30). CONCLUSIONS: This odds ratio
      estimate is consistent with a moderately strong association. Studies included did
      not adjust for possible confounders (e.g. prenatal care, cocaine or tobacco), so
      confounding is likely to account for at least some of the observed effect. The
      relative consistency of results from studies included in the meta-analysis that
      were conducted in different countries and at different times adds to the strength
      of the evidence for an association between opiate use and antepartum haemorrhage.
      Well designed studies are urgently required to assess the independent effects of
      different types and patterns of maternal opiate use and confounders such as
      cigarette smoking, illicit cocaine use and antenatal care on antepartum
      haemorrhage.

PMID- 9926561
TI  - Acute opiate overdose: characteristics of 190 consecutive cases.
AB  - AIMS: To characterize the population of drug users consulting the Emergency Room
      (ER) of a university hospital with acute opiate overdose (AOO) and to assess rate
      of referral to specialized treatment programme. DESIGN: Survey of a 12-month
      sample of AOO patients. MEASUREMENTS: Medical and psychosocial features of the
      drug users, details of emergency treatment and referral by a mobile resuscitation
      team (SMUR) and the ER of our hospital (CHUV-Lausanne, Switzerland). In addition
      fatal AOO cases were collected by the Institute of Forensic Medicine (IFM) during
      the same period. FINDINGS: One hundred and eighty-four cases of AOO (134
      patients) were treated. The files of the IFM detailed six additional deceased
      cases. This population of drug users was characterized by an over-representation
      of men (73%), by young age (27.4 years), by a high rate of multi-drugs use (90%)
      and by a high rate of multiple previous overdoses (2.6). Average length of stay
      was 20.1 hours but 41% of cases stayed less than 8 hours. Only one patient was
      readmitted within an 8-hour period. When discharged, 78% returned home.
      Unexpectedly, 67% of patients were not referred to any therapeutic programme for
      drug addiction. CONCLUSION: This study shows the low mortality of AOO when
      treated but also demonstrates the need to improve psychosocial evaluation and
      referral of drug addicts admitted with AOO.

PMID- 9926562
TI  - French general practitioners' attitudes toward maintenance drug abuse treatment
      with buprenorphine.
AB  - AIMS: To assess attitudes of general practitioners (GPs) toward buprenorphine
      maintenance drug abuse treatment just after its introduction in French ambulatory
      care (February, 1996). DESIGN: Cross-sectional survey by telephone interviews in
      a national random sample of French GPs (n = 1,186; response rate = 70.3%) carried
      out in April 1996. MEASUREMENTS: GPs' experience with care for IDU patients and
      HIV infection during the last 12 months. Logistic regression model to identify
      GPs' characteristics associated with readiness to prescribe buprenorphine for
      maintenance treatment. FINDINGS: A minority (24.0%) of GPs took care of IDU
      patients and 30.8% of these were prepared to prescribe buprenorphine (vs. only
      7.5% in the rest of the sample). A positive attitude toward buprenorphine was
      related to GPs' experience with care for IDUs and with prescription of opiates
      for pain management and palliative care, tolerance toward drug use and personal
      characteristics such as tobacco use and interest in psychoanalysis. CONCLUSIONS:
      Giving general freedom of prescription of buprenorphine (rather than methadone)
      to all GPs did not lead to widespread acceptance of the drug's use in treating
      IDUs. The development of organized networks between specialist services for drug
      abuse treatment and motivated GPs may be necessary to maximize appropriate
      prescribing practices.

PMID- 9926563
TI  - Drug use pathways among high school students of Mexico.
AB  - OBJECTIVE: This study surveyed high school student drug users in urban areas of
      Mexico to describe use patterns and drug-related behaviors among adolescents and
      to develop predictor models of pathways to underage drug use. SUBJECT/DESIGN: A
      National School Survey was conducted among high school students where data are
      provided by the State. Only urban sites were considered for this study (n =
      40,521). Stratified two-stage cluster sampling was used; schools and groups
      within the schools were the sampling units. CONCLUSIONS: Male adolescents who
      have worked the previous year, have high exposure within the family and are
      affiliated with drug using peers are at increased risk of becoming drug users and
      subject to depression and suicidal ideation as well as drug-related social
      problems.

PMID- 9926564
TI  - It can be bad for the heart, too--drinking patterns and coronary heart disease.

PMID- 9926565
TI  - Conversion with R. J. Hawke.

PMID- 9926566
TI  - Do treatment process factors mediate the relationship between type A-type B and
      outcome in 12-Step oriented substance abuse treatment?
AB  - AIMS: One underutilized strategy for enhancing treatment research is to examine
      intervening factors that link client characteristics to endpoint outcomes. This
      study tested the hypothesis that Type B substance abusers would demonstrate
      difficulties engaging in the treatment process, and that these problems would
      mediate their poorer outcomes. DESIGN: Longitudinal naturalistic study. SETTING:
      Two intensive 12-Step substance abuse treatment programs. PARTICIPANTS: A sample
      of 115 men and women seeking treatment. MEASUREMENT: Empirical clustering
      techniques were used to divide the sample, and the link between type, process
      factors, and 12-month outcomes was examined. FINDINGS: Hypotheses were not
      supported. Type Bs did not demonstrate difficulties with the treatment process,
      but had greater problems sustaining gains posttreatment. Contrary to prediction,
      Type Bs were better matched to self-help affiliation than Type As. CONCLUSIONS:
      Findings argue for a more optimistic perspective on treating Type Bs, and for the
      utility of Type A-Type B in informing treatment research.

PMID- 9926567
TI  - Differences between hospital patients with alcohol problems referred for
      counselling by physicians' routine clinical practice versus screening
      questionnaires.
AB  - AIMS: To test the hypothesis that screening for alcohol-related disorders in a
      general hospital with questionnaires generates a target group of patients for
      alcohol counselling which differs from patients referred by physicians' routine
      clinical practice. DESIGN: A prospective study with follow-up after 12 months.
      SETTING: Medical and surgical wards of a general hospital. PARTICIPANTS: A sample
      of 298 patients detected by screening questionnaires (CAGE, MAST) was compared
      with a sample of 87 patients referred by physicians. MEASUREMENTS: The main
      measurements were a diagnostic interview (SCAN), two questionnaires to estimate
      the severity of dependence and the motivation to change drinking behaviour (RCQ,
      LAS), and socio-demographic variables. Outcome criteria were utilization of
      remedial programmes, decreases in hazardous and excessive drinking and abstinence
      rates. FINDINGS AND CONCLUSIONS: Patients referred by physicians were more often
      separated and unemployed, were more likely to be alcohol-dependent and to be more
      severely dependent, had a higher rate of alcohol-related diseases as reasons for
      admission, were more often motivated to change drinking behaviour, had a higher
      participation rate in remedial programmes and more often exhibited improvements
      in drinking behaviour compared with the sample identified by screening
      questionnaires. However, there was evidence of improvements in drinking in both
      samples. Data show that while screening reaches a less problematic sample with
      lower motivation to change, it is a worthwhile activity which extends the
      spectrum of patients eligible for brief interventions.

PMID- 9926568
TI  - The relationship between childhood sexual abuse and alcohol abuse in women--a
      case-control study.
AB  - AIMS: The aim of this paper was to examine the association between reporting
      childhood sexual abuse (CSA) and alcohol abuse in a community sample of women
      using multivariate analysis which took into account a range of potential
      confounding variables (such as a family history of alcoholism) and effect
      modifiers (such as having an alcoholic partner). DESIGN: A two-stage
      retrospective case-control study was used to investigate the relationship between
      reporting CSA and alcohol abuse in women. PARTICIPANTS: Seven hundred and ten
      women randomly selected from the Australian federal electoral rolls.
      MEASUREMENTS: The Alcohol Use Disorders Identification Test (AUDIT) was used to
      measure alcohol abuse. A series of questions based on those developed by Wyatt
      (1985) were used to ascertain the prevalence of CSA. FINDINGS: The final model
      showed that the relationship between a history of CSA and alcohol abuse reflected
      a complex interaction between CSA and a range of other factors in a woman's
      background. CSA was not by itself a significant predictor of alcohol abuse (OR =
      0.61; 95% CI = 0.31-1.20). However, a history of CSA became significant in
      combination with co-factors which included: having a mother who was perceived as
      cold and uncaring; having an alcoholic partner; and believing that alcohol is a
      sexual disinhibitor. CONCLUSION: This study indicates that CSA alone is not a
      causative factor in the development of alcohol abuse among women and highlights
      the importance of examining the family background of women with alcohol problems.

PMID- 9926569
TI  - Tolerate, engage or withdraw: a study of the structure of families coping with
      alcohol and drug problems in south west England and Mexico City.
AB  - AIMS: To explore the structure underlying individual differences in the ways
      family members cope with drinking or drug problems. DESIGN: Cross-sectional
      interview and questionnaire study of a series of family members in two
      contrasting socio-cultural groups. SETTING: Mexico City and South West England.
      PARTICIPANTS: Two hundred and seven family members from separate families, three
      quarters women, one-quarter men, mostly partners or parents. DATA: Long semi
      structured interviews; the Coping Questionnaire (CQ). FINDINGS: Factor and
      subscale analyses of the CQ data and textual analysis of the interview reports
      were used to test the hypothesis that the underlying structure to coping could be
      described in terms of eight or nine coherent and distinct ways of coping. Neither
      form of analysis gave strong support to this hypothesis. CONCLUSIONS: It is
      concluded that the structure of coping can best be described in terms of three
      broad coping positions: tolerating, engaging and withdrawing. These conclusions
      challenge some previous assumptions about functional and dysfunctional ways of
      coping with excessive appetitive behaviour in the family.

PMID- 9926570
TI  - An analysis of alcohol policy in Hungary. Who is in charge?
AB  - AIM: In the light of unprecedented increases in the levels of chronic liver
      disease and cirrhosis in Hungary, accompanied by other evidence of increasing
      health and social consequences of alcohol, this study aimed to identify alcohol
      policy actors at the national level, describe their understanding of alcohol
      policy, determine their position, interest and influence on the issue, and
      identify the inter-relationships between these actors. METHODS: A series of
      interviews with key actors identified through a snowball technique, supplemented
      by a telephone survey of local government authorities. Analysis was undertaken
      according to the principles of stakeholder analysis and political mapping.
      FINDINGS AND CONCLUSIONS: The alcohol policy arena is fragmented. There is a lack
      of explicit and coherent goals and a shared vision by all actors is missing. Key
      actors do not seem to be aware of what they could do as a result of their
      position, and how. There is a failure to develop strategic alliances. Those
      actors with high and medium levels of support and interest in a comprehensive
      alcohol policy which would seek to control overall consumption have little
      influence. Those with influence in the policy arena have not mobilized themselves
      as regards public health in general and alcohol related policy in particular,
      with few notable exceptions. Considerable opposition can be expected from those
      working in retail and catering facilities.

PMID- 9926571
TI  - An examination of next-day hangover effects after a 100 mg/100 ml dose of alcohol
      in heavy social drinkers.
AB  - AIMS: Carry-over effects or the hangover hypothesis postulates that alcohol
      continues to impair performance the morning after drinking, even after low or
      moderate doses. Performance deficits have been attributed to the residual effects
      of recent drinking. The present study examined evidence for residual alcohol
      consumption on human performance when blood alcohol level has declined to zero.
      DESIGN: A within-subjects, repeated measures, placebo controlled experiment was
      conducted with double-blind alcohol administration to investigate the effects of
      alcohol the morning after ingestion. SETTING: All subjects were studied in
      Glasgow, Scotland, UK. PARTICIPANTS: Forty healthy male moderate to heavy social
      drinkers between 18 and 45 years of age. MEASUREMENTS: Psychomotor performance,
      subjective state and quality of sleep were examined under alcohol and placebo
      with a 1-week interval between test sessions. Enough alcohol was given to place
      subjects above the legal limit for driving at peak blood alcohol. FINDINGS: There
      was no evidence for impaired performance the morning after ingestion. Effects
      were found for subjective state and sleep quality. CONCLUSIONS: The findings
      suggest that after a 100 mg/100 ml dose of alcohol people who: (a) have no
      alcohol left in their blood and; (b) do not feel hung over will generally be fit
      to drive.

PMID- 9926572
TI  - Illicit drug use among Mexicans and Mexican Americans in California: the effects
      of gender and acculturation.
AB  - AIMS: To examine the effects of gender and acculturation on illicit drug use
      among the Mexican-origin population in California. DESIGN: The 3012 subjects
      between 18 and 59 years of age were selected under a stratified, multi-stage
      cluster sampling method. SETTING: Fresno County in California is primarily
      agricultural, with only one metropolitan area. Over 30% of the total population
      of 764,800, are Hispanics, of Mexican origin. MEASUREMENTS: A modified version of
      the World Health Organization's Composite International Diagnostic Instrument
      (WHO-CIDI) was used to ascertain drug use. Respondents were considered drug users
      if they had ever used marijuana, cocaine, hallucinogens, heroin or inhalants.
      Acculturation was measured with a Likert scale, assessing English vs. Spanish
      language preference. Other covariates of interest were nativity and place of
      residence. FINDINGS: Men had higher rates of use than women for every drug (men =
      46.3%, women = 23.2%). Urban rates were higher than rural rates, for both women
      (urban = 32.8% vs. rural = 16.6%) and men (urban = 57.0% vs. rural = 36.8%). In
      logistic regression models, men were more likely than women to have ever used
      illicit drugs or inhalants (adjusted OR = 4.8), cocaine (adjusted OR = 5.3) or
      marijuana (OR = 4.3). However, the combined effect of United States nativity and
      acculturation, on drug use, was greater among women (adjusted OR = 29.3) than
      among men (adjusted OR = 7.4). The effect of acculturation was stronger among
      urban, than among town or rural residents. CONCLUSIONS: Acculturation and United
      States nativity are risk factors for illicit drug use among Mexican origin men
      and women. However, women have increased vulnerability compared with men.
      Findings reinforce the need for culturally based public health interventions.

PMID- 9926573
TI  - Substance misusers remanded to prison--a treatment opportunity?
AB  - AIMS: To describe self-reported levels of substance misuse before arrest among
      remanded prisoners (unconvicted prisoners awaiting trial), to assess their degree
      of dependency on opiates and stimulants and to record their experiences of
      treatment in prison. DESIGN: Random selection of subjects from prisons chosen to
      give a geographical spread across England and Wales; self-report at semi
      structured interview, plus examination of the prison medical record. SETTING:
      Thirteen male prisons, three Young Offenders' Institutions and three womens'
      prisons. PARTICIPANTS: Nine hundred and ninety-five consenting, unconvicted
      prisoners, randomly selected from all locations within the prisons: 750 men (9.4%
      sample) and 245 women (82.2% of all remanded women). MEASUREMENTS: CAGE
      Questionnaire, Severity of Dependence Scales (SDS) for daily users of opiates
      and/or stimulants. FINDINGS: Before arrest, 145 (19.3%) men and 72 (29.4%) women
      had been dependent on street drugs; 91 (12.1%) men and 16 (6.5%) women were
      solely dependent on alcohol. Seventeen (2.3%) men and four (1.6%) women reported
      injecting drugs during this imprisonment. Mean SDS scores were 10.6 for opiate
      and 7.7 for stimulant users. 244 (25%) of all subjects described withdrawal
      symptoms on reception into custody; 157 (16%) reported being prescribed some
      symptomatic relief; 235 (24%) requested treatment at interview. CONCLUSIONS: By
      extrapolation, 1905 people--23% of all unconvicted prisoners--want treatment for
      substance misuse. This apparent shortfall in provision must be addressed; the
      rapidity with which remanded prisoners return to the community dictates that
      prison and community services should be closely linked.

PMID- 9926574
TI  - The Maudsley Addiction Profile (MAP): a brief instrument for assessing treatment
      outcome.
AB  - AIM: To develop a brief, multi-dimensional instrument for assessing treatment
      outcome for people with drug and/or alcohol problems. The Maudsley Addiction
      Profile (MAP) is the first instrument to be developed in the United Kingdom for
      this purpose. DESIGN: Field testing with quota-recruitment of problem drug users
      and problem alcohol users in treatment with researcher and clinician-administered
      test-retest interviews. SETTING: Two community and two inpatient services at the
      Bethlem Royal and Maudsley Hospital, London. PARTICIPANTS: Subjects (160 drug
      users and 80 alcohol users) interviewed by eight interviews (four researchers and
      four clinicians), each of whom interviewed 30 subjects on two occasions.
      MEASURES: Sixty items across substance use, health risk, physical/psychological
      health and personal/social functioning domains. FINDINGS: Average completion time
      of the MAP was 12 minutes. The questionnaire was acceptable to a majority of
      subjects and performed well with both researcher and clinician interviewers.
      Internal reliability and feasible concurrent validity assessments of the scales
      and items were highly satisfactory. Test-retest reliability was good, average
      intraclass correlation coefficients across eight substances were 0.94 and 0.81
      across health risk, health problems, relationship conflict, employment and crime
      measures. CONCLUSIONS: The MAP can serve as a core research instrument with
      additional outcome measures added as required. The collection of a set of
      reliable quantitative measures of problems among drug and alcohol users by
      research or treatment personnel for outcome evaluation purposes need not be time
      consuming.

PMID- 9926575
TI  - Is mental health in childhood a major predictor of smoking in adolescence?
AB  - AIMS: To test an extended version of Pomerleau's (1997) hypothesis that children
      with mental health problems are at higher risk of smoking in preadolescence and
      adolescence. DESIGN: Information concerning mental health from 5 to 13 years,
      smoking at ages 11 and 15, and family disadvantage at age 7 was available for 773
      children enrolled in a longitudinal study of children and adolescents.
      PARTICIPANTS: Participants were enrolled into the Dunedin Multidisciplinary
      Health and Development Study, which is a longitudinal investigation of the
      health, development and behaviour of a large group of New Zealand children born
      between 1 April 1972 and 31 March 1973. MEASUREMENTS: Assessment of mental health
      problems in childhood was based upon parent and teacher reports of behavioural
      and emotional problems. In pre-adolescence, mental health was assessed by self,
      parent and teacher report. Smoking was assessed by self-report. FINDINGS: None of
      the potential risk factors of gender, childhood disadvantage or childhood mental
      health problems predicted onset of smoking in pre-adolescence. Daily smoking at
      age 15 was best predicted by smoking in preadolescence, being female and
      experiencing childhood disadvantage. Pre-adolescent mental health was only weakly
      predictive of later smoking and this association appeared to be confounded with
      background disadvantage. CONCLUSIONS: We found little support for the extension
      of Pomerleau's (1997) hypothesis to childhood mental health. Our findings also
      run counter to recent suggestions for targeting smoking prevention at groups of
      children with mental health disorders.

PMID- 9926576
TI  - Project Charlie.

PMID- 9926577
TI  - Is mental health in childhood a major predictor of smoking in childhood.

PMID- 9926578
TI  - A nine year old who still wets the bed.

PMID- 9926579
TI  - Key developments in neurology.

PMID- 9926580
TI  - Effective treatments for migraine.

PMID- 9926581
TI  - Parkinson's: a strategy for management.

PMID- 9926582
TI  - TIAs and mild stroke: prevention is the key.

PMID- 9926583
TI  - Diagnosis and care of epilepsy.

PMID- 9926584
TI  - Phimosis.

PMID- 9926585
TI  - A rational strategy for influenza.

PMID- 9926586
TI  - Diagnosing and managing eyelid problems.

PMID- 9926587
TI  - When should you suspect pancreatitis?

PMID- 9926588
TI  - Dealing with a dizzy patient.

PMID- 9926589
TI  - An elderly woman with signs of osteoporosis.

PMID- 9926590
TI  - Minimising risk in contraception.

PMID- 9926592
TI  - Action plans for safe prescribing.

PMID- 9926591
TI  - Emergencies: communication is key.

PMID- 9926595
TI  - An effective strategy for sleep.

PMID- 9926596
TI  - Ethnicity and psychiatry.

PMID- 9926593
TI  - Addressing common dilemmas in contraception.

PMID- 9926594
TI  - Key developments in family planning.

PMID- 9926597
TI  - Preparing for the new MRCGP examination.

PMID- 9926598
TI  - Nasal polyps: treat or refer?

PMID- 9926599
TI  - Who's being irresponsible?

PMID- 9926600
TI  - A patient with heart disease plans a long flight.

PMID- 9926601
TI  - Key developments in the battle against infection.

PMID- 9926602
TI  - When is it right to prescribe in URTI?

PMID- 9926603
TI  - When to prescribe in lower respiratory tract infection?

PMID- 9926605
TI  - A guide to fungal skin infections.

PMID- 9926604
TI  - Diagnosing and treating scabies.

PMID- 9926606
TI  - Food poisoning: the increase is genuine.

PMID- 9926607
TI  - Breast cancer: who is at risk?

PMID- 9926608
TI  - A rational approach to osteoarthritis.

PMID- 9926609
TI  - Prepare yourself for paper 2.

PMID- 9926610
TI  - Making the medicine fit the patient.

PMID- 9926611
TI  - Assessing the effects of cooperation bias and attrition in behavioral genetic
      research using data-weighting.
AB  - Because twins and adoptees are a rare resource, they are often studied repeatedly
      over a period of many years. Differential attrition, and in some studies initial
      cooperation bias, have the potential to lead to serious biases to estimates of
      genetic and environmental parameters. Since non-response is often influenced by
      multiple binary or categorical sociodemographic variables, maximum-likelihood
      methods are not easily adapted to adjust for such effects. In this brief note we
      illustrate the use of data-weighting to assess the likely effects of cooperation
      bias or attrition both on measures of mean or prevalence, and on twin pair
      correlations or concordances, using data from the Australian twin panel 1981
      survey and alcohol challenge studies. Participants in the alcohol challenge study
      were on average younger, more socially nonconforming, heavier drinkers, more
      likely to be unmarried, and less likely to report their religion as Other
      Protestant. Reweighting the alcohol challenge sample to have the same
      distribution on these variables as the Australian twin panel 1981 survey
      respondents confirmed that individuals who would feel very intoxicated after a
      challenge dose of alcohol were underrepresented in the study. However, pairwise
      data-weighting indicated that this cooperation bias was leading to only a slight
      underestimation of the importance of genetic effects on subjective intoxication.

PMID- 9926612
TI  - Correcting estimates of shared environmental variance for range restriction in
      adoption studies using a truncated multivariate normal model.
AB  - A model is presented for the truncated trivariate normal distribution that arises
      in behavior genetic adoption designs that focus on sibling similarity to estimate
      shared environmental effects. The model estimates the point of truncation and
      shared environmentality. Both moment and maximum likelihood estimates are
      obtained numerically. Simulations indicate that the model and the numerical
      procedures perform well when they are most needed, that is, when shared
      environmentality is large, truncation is extensive or both. When applied to
      published data from the Texas Adoption Project, results indicate that the point
      of truncation is at about the 63rd percentile of the family environmental quality
      distribution (i.e., the bottom 63% is missing) and shared environmentality is
      about 55%. Implications for current views on the importance of shared environment
      for child developmental outcomes such as antisocial behavior and IQ are
      discussed.

PMID- 9926613
TI  - Genetic and environmental influences on EEG coherence.
AB  - EEG coherence measures the covariation in electrical brain activity between two
      locations on the scalp and is used to study connectivity between cortical
      regions. The aim of this study was to determine the heritability of EEG
      coherence. Coherence was measured in a group of 213 16-yr-old twin pairs. By
      including male and female twin pairs in the sample, sex differences in genetic
      architecture were systematically examined. The EEG was obtained during quiet
      supine resting. Coherence was estimated for short and long distance combinations
      of electrode pairs along the anterior-posterior axis within a hemisphere for four
      frequency bands (delta, theta, alpha and beta). Averaged over all electrode
      combinations about 60% of the variance was explained by genetic factors for
      coherence in the theta, alpha and beta bands. For the delta band, the
      heritability was somewhat lower. No systematic sex differences in genetic
      architecture were found. All environmental influences were nonshared, i.e.,
      unique factors including measurement error. Environmental factors shared by twin
      siblings did not influence variation in EEG coherence. These results suggest that
      individual differences in coherence form a potential candidate for (molecular)
      genetic studies on brain function.

PMID- 9926614
TI  - Genetic analysis of Drosophila sechellia specialization: oviposition behavior
      toward the major aliphatic acids of its host plant.
AB  - Oviposition behavior of the four species in the Drosophila melanogaster complex
      (D. melanogaster, D. simulans, D. mauritiana, D. sechellia) was investigated
      versus natural morinda fruit (the normal resource of D. sechellia) and the two
      major aliphatic acids of this fruit (hexanoic acid, C6, and octanoic acid, C8).
      Two different experimental techniques were compared. When control and
      experimental food were set on the same egg laying plate, three species (D.
      sechellia, D. mauritiana, D. melanogaster) exhibited a significant preference for
      morinda; with aliphatic acids, only D. sechellia manifested a preference. With
      separate oviposition sites, a preference was found in D. sechellia for morinda
      and acids, and a general avoidance behavior in the three other species. Genetic
      analysis of the behavioral response toward C6 and C8 was done with the two plates
      technique on D. sechellia, D. simulans, F1 hybrids and backcrosses. Significant
      behavioral differences were observed with major effects due to genotype,
      concentration and their interaction. Hybrid behaviors were intermediate between
      those of their parents. In several cases, a qualitative reversal from preference
      to avoidance was observed with increasing concentration. In F1 flies, a dominance
      reversal was observed with increasing C8 concentration. Different reaction
      thresholds in different receptors might explain such observations.

PMID- 9926615
TI  - A comparison of power to detect a QTL in sib-pair data using multivariate
      phenotypes, mean phenotypes, and factor scores.
AB  - The power to detect a quantitative trait locus (QTL) in sib-pair data is
      investigated. We assume that we have at our disposal 3 or 4 related phenotypic
      measures in a sample of sib-pairs. Individual differences in these phenotypes are
      due to a common QTL and specific (i.e., unique to each phenotype) nonshared
      environmental and specific polygenic additive effects. In addition, models are
      considered that include common nonshared environmental effects and/or common
      polygenic additive effects. We calculate the power to detect the QTL in a genetic
      covariance structure analysis of the multivariate data, of the mean phenotypic
      data, and of factor scores. The use of factor scores is shown to be universally
      more powerful than the use of multivariate or mean phenotypic data. We also
      investigate the effect of using a single sample of sib-pairs to both calculate
      the factor score regression matrix and to carry out the QTL analysis. The use of
      a single sample to both these ends results in a loss of power compared to the
      theoretical, expected power. The gain in power attributable to the use of factor
      scores, however, outweighs this observed loss in power. The advantages of using
      factor scores in selecting sib-pairs are discussed.

PMID- 9926616
TI  - Iteratively reweighted least squares mapping of quantitative trait loci.
AB  - Mapping quantitative trait loci (QTL) is a typical problem of regression with
      uncertain independent variables because the genotype of a putative QTL is not
      observed. Rather, the genotype is inferred from marker information. The method of
      maximum likelihood (ML) methods is considered to be the optimal solution for this
      problem because the distribution of the unobserved QTL genotype is fully taken
      into account. The simple linear regression method (REG) is a first-order
      approximation to ML and usually performs very well. In this study, an iteratively
      reweighted least squares method (IRWLS) is proposed. The new method is a second
      order approximation to ML because both the expectation and the variance of the
      unobserved QTL genotype are taken into consideration. The IRWLS is developed in
      the context of a single large outbred family. The properties of IRWLS are
      demonstrated and compared with REG and ML via replicated Monte Carlo simulations.
      The conclusions are: (1) when marker information content is high, the three
      methods perform equally well, but ML and IRWLS outperform REG when marker
      information content is low and the variance explained by the QTL is high; (2)
      when the residual distribution is not normal, ML can fail or have low power to
      detect small QTLs, but REG and IRWLS are robust to non-normality; and (3) when
      the residual distribution is normal, the performance of IRWLS is almost identical
      to ML, but the computational speed of IRWLS is many times faster than that of ML.

PMID- 9926617
TI  - Increase in power through multivariate analyses.
AB  - Power to detect genetic and environmental influences increases not only with
      sample size but also with the number of measurements through longitudinal and/or
      multivariate designs, if those measurements correlate with each other. Power
      simulations are presented for uni- through quadrivariate cases, with differing
      genetic and environmental parameters. Even though subject attrition is a problem
      for most longitudinal studies, the gain in power available may more than make up
      for this shortcoming in many situations. In terms of planning studies to examine
      genetic and environmental influences, power calculations should not only consider
      sample size but number of measurements on particular phenotypes and their
      intercorrelations.

PMID- 9926618
TI  - Longitudinal genetic analysis of problem behaviors in biologically related and
      unrelated adoptees.
AB  - The genetic and environmental influences on problem behaviors at two assessment
      points, three years apart, and their stability were studied in a sample of
      international adoptees, initially aged 10 to 15 years. Parents of 111 pairs of
      adopted biological siblings, 221 pairs of adopted nonbiological siblings and 1484
      adopted singletons completed the Child Behavior Checklist (75 pairs, 154 pairs
      and 1080 singletons respectively at second assessment). At first assessment,
      genetic factors accounted for more than 50% of the variance in the Externalizing,
      Aggressive Behavior, Attention Problems and Social Problems scales. Shared
      environmental influences explained 40% of the variance in the Total Problem scale
      and less for all other scales. Nonshared environmental influences were most
      important for the Internalizing scale and its subscales, and for the Thought
      Problems and Delinquent Behavior scales. At the second assessment, genetic
      factors explained most of the variance in the Total Problem, Externalizing and
      Aggressive Behavior scales, while nonshared environmental influences explained
      most of the variance in all other scales. Shared environmental influences
      explained 33% of the variance in the Internalizing scale and less for the other
      scales. The stability of the Externalizing scale over time was caused mostly by
      genetic factors, while nonshared environmental factors mostly caused the
      stability of the Internalizing scale.

PMID- 9926619
TI  - Molecular manipulations of extracellular superoxide dismutase: functional
      importance for learning.
AB  - Extracellular superoxide dismutase (EC-SOD) controls the availability of
      extracellular superoxide (O2.-), which is important for a variety of
      physiological pathways, including the primary means of inactivating nitric oxide
      (NO). The role of EC-SOD in neurobehavioral function has been until now
      unexplored. In the current studies, the phenotypic expression of genotypic
      alterations of EC-SOD production in mice were characterized for spatial learning
      and memory. Dramatic impairments in spatial learning in the win-shift 8-arm
      radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing
      mice. The EC-SOD overexpressing mice were further characterized as having
      significant deficits in a repeated acquisition task in the radial-arm maze, which
      permitted the dissociation of long and short-term learning. Long-term learning
      was significantly impared by EC-SOD overexpression, whereas short-term learning
      was not significantly affected by EC-SOD overexpression. No systems have been
      shown to be importantly involved in learning and memory. This may be important in
      the current studies because EC-SOD has primary control over the inactivation of
      NO. We found that EC-SOD overexpressing mice were resistant to the cognitive
      effects of L-NAME (NG-nitro-L-arginine methyl ester hydrochloride), an NO
      synthase inhibitor. Decreased NO catabolism in these mice may have served to
      counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD
      levels that were either higher or lower than controls impaired learning
      demonstrates that the proper control of brain extracellular O2.- may be more
      vital than merely reduction of brain extracellular O2.- in maintaining adequate
      learning function.

PMID- 9926620
TI  - Courtship bout duration in per circadian period mutants in Drosophila
      melanogaster.
AB  - Mutations on the period locus of Drosophila melanogaster influence circadian
      periods as well as the rhythm in inter-pulse intervals in male courtship song;
      perL mutations produce long circadian periods and courtship song rhythms and
      per(s) mutations produce short circadian periods and courtship song rhythms.
      Thus, these mutations influence timing mechanisms over both long and short
      behavioral time horizons. We examined if the mean courtship duration of male
      Drosophila melanogaster cycles rhythmically, and if mutations at the period locus
      influence courtship bout duration. We measured the courtship bout durations of
      the following: (1) wild type Canton-S (per+) males; (2) perL males; and (3)per(s)
      males. Rhythmicity of courtship bout duration could not be mathematically
      determined. Mean courtship bout duration did not differ among the three groups;
      thus, mutations at the period locus did not influence mean courtship duration.
      There was a nonsignificant trend for per+ males that were successful at mating to
      have longer mean courtship duration than unsuccessful males.

PMID- 9926621
TI  - How does offspring quality change with age in male Drosophila melanogaster?
AB  - We examined the relationship of genetic quality to age in male Drosophila
      melanogaster to test two contrasting hypotheses. The traditional hypothesis is
      that older males have proven their viability and therefore produce offspring of
      superior genetic quality. This hypothesis is often evoked as an explanation for
      female preference for older mates. In contrast, we have recently argued that
      older fathers may produce offspring of inferior genetic quality. Here, we present
      results from an experiment designed to measure the genetic quality of offspring
      produced by 2 day old, 2 week old and 5 week old male D. melanogaster. We found a
      statistically significant small reduction in larval viability and a similar but
      statistically non-significant reduction in son mating ability among the offspring
      of the 5 week old males. Daughter fecundity showed no apparent trend for a
      reduction nor an increase in performance with increasing age of the fathers.
      There was no evidence of a difference between the 2 day old and the 2 week old
      males for any of these three fitness components. These results are in somewhat
      better accordance with our alternative hypothesis, but the relatively weak and
      late occurring effects indicate that mate choice based on age may not be a viable
      strategy in this population.

PMID- 9926622
TI  - A chromosomal analysis of the phenotypic plasticity of some life history traits
      in relation to developmental temperature.
AB  - The capacity to delay egg deposition in D. melanogaster females in the absence of
      a sexual partner is genetically determined and opposite types can be artificially
      selected. In natural populations, the relative frequency of these genotypes
      varies geographically and seasonally, with temperature as a selective factor.
      However, the retention duration of these genotypes can be modified by
      developmental temperature change. To study the genetic control of this response,
      chromosome substitution between opposite types of line was carried out in order
      to produce every possible homozygous chromosomal combination of the three major
      chromosomes (X,2,3). Eggs of these eight constructed lines were developed at two
      different temperatures (25 degrees C and 14 degrees C). Low temperature
      development directly affected the number of ovarioles but also modified the
      subsequent expression of adult characteristics such as retention duration and
      fecundity. The comparison of the eight lines revealed that, although the 3
      chromosomes were involved in the genetic determinism of each trait, only one or
      two of them were sensitive to temperature change, and these differed according to
      the trait. For retention duration and fecundity, the effect of chromosome 3 from
      the long retention strain was particularly affected by low temperature, showing
      antagonism between the selective effect detected in natural populations and the
      effect on phenotypic plasticity studied here.

PMID- 9926623
TI  - Human transmissible spongiform encephalopathies.

PMID- 9926624
TI  - Surveillance for Creutzfeldt-Jakob disease in Canada.

PMID- 9926625
TI  - Deep brain stimulation reduces symptoms of Parkinson disease.
AB  - Surgical ablation or continuous electrical stimulation of specific areas deep in
      the brain may help patients with Parkinson disease or other movement disorders
      for whom medications have failed or who experience dose-limiting side effects
      from medications.

PMID- 9926626
TI  - A 47-year-old man with leiomyosarcoma and altered mental status.

PMID- 9926627
TI  - Underused options for preventing and treating influenza.
AB  - Both amantadine and rimantadine are effective for preventing and treating
      influenza A, particularly in high-risk patients. However, they should be used
      judiciously due to the risk of central nervous system side effects and drug
      interactions. Zanamivir, a new agent for treating influenza, offers promise but
      needs further study and approval by the Food and Drug Administration before it
      can be recommended for routine use. Influenza vaccine, the most effective
      preventive measure, is widely underused.

PMID- 9926628
TI  - Zinc lozenges for the common cold.
AB  - The scientific basis for zinc treatment of the common cold is debatable, and
      clinical trials of zinc cold therapy have produced conflicting results. This
      review summarizes the current basic and clinical knowledge of zinc for the common
      cold, and suggests the present role of zinc therapy and future research needs.

PMID- 9926629
TI  - The breast cancer prevention trial (P-1 study). The role of tamoxifen in
      preventing breast cancer.
AB  - The recently completed Breast Cancer Prevention Trial found that tamoxifen can
      reduce the incidence of breast cancer by nearly half in women at high risk, but
      the benefit comes at a price of increased risk of endometrial cancer and
      thromboembolism. This article reviews the actions of tamoxifen and the design,
      findings, and implications of this study.

PMID- 9926630
TI  - Constipation: an approach to diagnosis, treatment, referral.
AB  - When a patient reports constipation, a careful history and physical examination
      may identify the underlying cause. In many patients, though, no underlying cause
      is identified. Empiric treatment with exercise, hydration, fiber supplementation,
      and mild laxatives is often effective. If constipation does not resolve with
      these measures, then the physician may refer the patient for further testing for
      slow colonic transit, pelvic floor dysfunction, or anatomical defects, and in
      difficult and recalcitrant cases for surgical treatment.

PMID- 9926631
TI  - Complications of sickle cell anemia in adults: guidelines for effective
      management.
AB  - Thanks to improved treatment, most patients with sickle cell disease now survive
      long into adulthood, but they still face a lifetime of complications and crises,
      including chronic hemolytic anemia, vascular occlusions, pain, and the side
      effects of therapy. This article consists of guidelines for diagnosing and
      treating problems encountered in adult patients with sickle cell disease.

PMID- 9926632
TI  - Diagnosis and management of superior vena cava syndrome.
AB  - Superior vena cava (SVC) syndrome is a relatively common complication of lung
      cancer or lymphoma, and in fact is often the initial manifestation of these
      diseases. However, benign causes also exist, and physicians should not
      automatically assume that SVC syndrome is due to cancer. A definitive histologic
      diagnosis of cancer should be obtained before starting radiotherapy or
      chemotherapy to treat SVC syndrome.

PMID- 9926633
TI  - Space analysis: a comparison between sonic digitization (DigiGraph Workstation)
      and the digital caliper.
AB  - The introduction of the DigiGraph Workstation permits the use of sonic
      digitization to measure lateral cephalometric values, mesiodistal tooth size and
      arch perimeter discrepancy as a one-stop diagnostic record taking set-up. This
      study compared the reproducibility of mesiodistal total tooth widths and arch
      perimeter values, on plaster casts, given by the DigiGraph Workstation and by
      digital calipers. Forty-seven sets of plaster casts of Southern Chinese children
      (mean age 12.5 years) comprised the sample. Arch perimeter was measured using
      calipers in six segments from the distal of the first permanent molar to its
      antimere in each arch. The total mesiodistal widths of all teeth, excluding
      second and third molars, were also measured. The difference between the available
      arch perimeter and the total tooth widths was taken as the arch perimeter
      discrepancy. Sonic digitization of the study casts was completed according to
      instructions of the DigiGraph software. Paired t-tests and F-tests were used to
      compare the two methods. Compared with manual measurement, there was an over
      estimation of the total tooth widths by 1 mm in the mandible and 0.5 mm in the
      maxilla, and an arch perimeter discrepancy of 1.6 mm in the mandible and 0.4 mm
      in the maxilla when using the sonic method. The sonic digitization was not as
      reproducible as the digital caliper and its clinical usefulness in evaluating the
      space problem of an individual malocclusion should be interpreted with caution.

PMID- 9926634
TI  - A prospective evaluation of Bass, Bionator and Twin Block appliances. Part II-
      The soft tissues.
AB  - A prospective clinical study with a random allocation of 47 patients to three
      different functional appliance groups was established and compared with a
      slightly younger control group over a 9-month period. The cephalometric hard
      tissue changes were assessed in relation to the soft tissue changes produced and
      the patients were also assessed by three-dimensional (3D) laser scanning of the
      facial soft tissues. Each 'averaged' appliance group scan was compared with the
      'averaged' control group face. Statistically and clinically significant changes
      occurred in the group treated with the Twin Block appliance, and to a lesser
      extent in the group treated with the Bionator appliance. No statistically
      significant facial soft tissue changes could be demonstrated in the Bass
      appliance group. Upper lip position remained stable despite the significant
      overjet reduction attained in the three appliance groups. Lower lip protrusion
      (up to 3.8 mm), lower lip length (up to 4.0 mm), and soft tissue lower and total
      face height increased significantly in all appliance groups by varying amounts.
      The long-term effect of these changes needs to be fully evaluated. The laser
      scanning system was found to be a sensitive and accurate method of quantitatively
      assessing small changes in the soft tissue facial form. Significant changes of
      the facial tissues in the transverse plane were highlighted by this technique.

PMID- 9926635
TI  - Head posture and malocclusions.
AB  - The present study aimed to examine whether any pattern of associations could be
      found between the posture of the head and neck, and the occurrence of
      malocclusions. The sample comprised 96 children (45 M, 51 F) aged 7-13 years,
      sequentially admitted for orthodontic treatment of severe malocclusions.
      Malocclusions were diagnosed clinically and classified into occlusal, spacing,
      and dentitional anomalies and their subdivisions. Craniovertical, craniocervical,
      and cervicohorizontal postural variables were recorded from lateral cephalometric
      radiographs taken with the subject standing with the head in the natural head
      position (mirror position). A clear pattern of associations between crowding and
      craniocervical posture was found. Subjects with anterior crowding, i.e. more than
      2 mm lack of space in the upper or lower anterior segments of the dental arch,
      had craniocervical angles that were on average 3-5 degrees larger than subjects
      without crowding (P < 0.05, P < 0.01). The findings were in agreement with the
      soft tissue stretching hypothesis, according to which the sagittal development of
      the dentoalveolar arches is impeded by the increased dorsally-directed soft
      tissue pressure in subjects with extended craniocervical posture.

PMID- 9926636
TI  - Reference structures for assessment of frontal head posture.
AB  - The aim of the study was to test (a) the validity of the supra-orbital line as a
      substitute for the interpupillary line, and (b) the reproducibility of two
      different approaches of assessing cranio- and cervico-vertical relationships on
      frontal cephalograms. The material consisted of natural head position frontal
      cephalograms of 21 healthy Finnish students and 11 Danish young adults prepared
      according to a method described previously, modified in the Danish sample by
      addition of spectacles with a wire to indicate the interpupillary line. The
      cephalograms were analysed manually twice by two investigators with an interval
      of one week. The following reference lines were selected: (1) orbital line (ORB):
      a tangent to the extreme cranial point on the supra-orbital margins; (2) cranial
      line (CR): the line drawn through crista galli and anterior nasal spine; (3)
      cervical line (CER): a line drawn through the midpoints of atlas (half the
      distance between the most median points on the tubercle of the transverse
      ligament), and C4 (half the distance between the most concave points of the
      lateral masses); (4) the main course of the upper cervical spine (SPINE): a
      subjective impression of the spinal inclination; (5) the interpupillary line
      (IP); and (6) the true vertical and horizontal lines (VER, HOR). The angles were
      measured to the nearest 0.5 degrees. Intra- and inter-examiner reproducibility
      was calculated. The supra-orbital line almost coincided with the interpupillary
      line as the mean inclination between the lines was only 0.5 degrees. Both intra-
      and inter-examiner errors were less for ORB and CER than for CR and the line
      indicating the main course of the upper cervical spine (SPINE). The intra
      examiner reproducibility s(i) for ORB/HOR and CR/VER was 0.4 and 0.8 degrees
      respectively, and for CER/VER and SPINE/VER 0.8 degrees and 1.0 degrees. Based on
      these results, the supra-orbital line and the cervical line (defined as the mid
      transversal line between the atlas and the fourth cervical vertebra) are
      recommended as reference lines for assessing frontal head posture.

PMID- 9926637
TI  - Adolescent female craniofacial morphology associated with advanced bilateral TMJ
      disc displacement.
AB  - The aim of this study was to determine if cephalometric measurement differences
      occurred between two groups of similarly aged female adolescents which differed
      with respect to their diagnoses of temporomandibular joint disc position on
      magnetic resonance images (MRI). One group consisted of 17 female adolescents
      exhibiting complete bilateral disc displacement affecting the temporomandibular
      joints (TMJ), while the second group of 17 female adolescents was diagnosed as
      having bilateral normal disc position on MRI. Independent sample t-tests
      identified statistically significant differences in cephalometric measurements
      between the two groups, but no age difference between the two groups was evident.
      The group with bilateral total disc displacement exhibited the following
      significant angular differences from the group with normal disc position: an
      increased mandibular and palatal plane relative to sella-nasion; posterior
      rotation of the mandible as illustrated by an increased angle between the
      posterior border of the mandibular ramus and sella-nasion; and a decrease in
      Rickett's facial axis. Significant differences in linear cephalometric variables
      were also evident between the two groups. Total posterior facial height and ramus
      height were reduced in the totally disc displaced group. Furthermore, a slight
      increase in the middle anterior facial height was noted, with a decrease in the
      posterior cranial base vertical height in the totally disc displaced group.

PMID- 9926638
TI  - An ultrasound investigation of the lip levator musculature.
AB  - The aims of this study were to determine if there were any differences in the
      thickness of the lip levator musculature in men and women, and whether the height
      of the smile line in adults was related to the thickness of the lip levator
      musculature. Thirty Caucasian (13 males, 17 females), and 24 Asian (11 males, 13
      females) undergraduate dental students participated in this study. The subjects
      were placed in high, medium, and low smile-line groups, according to the height
      of their upper lip while smiling. The thickness of the levator labii superioris
      and zygomaticus major muscles was measured on ultrasound scans of the relaxed
      muscles. Gender, right-left side, and ethnic differences in muscle thickness were
      determined, and the thicknesses of the lip levator musculature in subjects in the
      high, medium, and low smile-line groups were compared. There were significantly
      more women than men with high smile-lines and the zygomaticus major muscle was
      significantly thicker in the women, as compared with the men. There were,
      however, no statistically significant differences in muscle thickness in the
      three smile-line groups. While it appears that women have higher smile-lines and
      significantly thicker zygomaticus major muscles than men, the height of the smile
      line is not due to the thickness of either the levator labii superioris or
      zygomaticus major muscles.

PMID- 9926639
TI  - Assessing incisor inclination: a non-invasive technique.
AB  - A method of recording incisor inclination is described using the Tooth
      inclination Protractor (TIP). This instrument was used to record incisor
      inclination on dental casts. The scores were related to traditionally determined
      inclinations for the upper incisor to maxillary plane and the lower incisor to
      mandibular plane from the lateral cephalometric radiograph. The TIP scores were
      closely related to the upper incisor to maxillary plane angle and lower incisor
      to mandibular plane angle. There was a systematic bias between the TIP and
      radiographically determined assessments. The TIP under-scored the lateral
      cephalometrically determined maxillary incisor inclination by 10.46 degrees and
      consistently over-scored the lower mandibular incisor angulation by 2.57 degrees.
      The TIP is a reliable and valid measure for assessing left and right maxillary
      and mandibular crown inclinations, and may also be used to record changes of
      incisor inclination during treatment.

PMID- 9926640
TI  - The early reparative process of orthodontically induced root resorption in
      adolescents--location and type of tissue.
AB  - The aim of this investigation was to determine the pattern of repair of root
      resorption regarding the location and type of tissue in adolescents after
      application of a well-controlled force magnitude. In 16 adolescents (mean age
      13.8 years), the maxillary first premolars were buccally moved with a weekly
      reactivated force of 50 cN (approximately 50 g) for 6 weeks following which the
      appliance was made passive for 2, 3, 6, and 7 weeks. The subjects were divided
      into two groups of eight individuals for which the retention periods were 2 and 6
      weeks (Group I), or 3 and 7 weeks (Group II), implying intra-individual
      differences of 4 weeks. Reparative cementum in the resorption cavities was seen
      in all test teeth, significantly more often after 6 and 7 weeks of retention (82
      per cent) compared with 2 and 3 weeks (35 and 44 per cent, respectively). The
      reparative process appeared to commence in the bottom of the resorption cavity,
      frequently covered by a thin layer of acellular cementum. However, most of the
      reparative cementum was of the cellular type and always covered the initially
      formed acellular cementum. There were great individual variations regarding the
      occurrence of healing of orthodontically-induced root resorption.

PMID- 9926641
TI  - Crisis facing HCFA & millions of Americans.

PMID- 9926642
TI  - Health care for the elderly: how much? Who will pay for it?
AB  - Health care expenditures on the elderly tend to grow about 4 percent per year
      more rapidly than the gross domestic product (GDP). This could plunge the nation
      into a severe economic and social crisis within two decades. This paper describes
      recent growth in age/sex-specific health care utilization by the elderly and
      discusses the important role of technology in that growth. It also explores the
      potential for the elderly to pay for additional care through increases in work
      and savings. Efforts to "save Medicare" will prove to be "too little, too late"
      unless they are embedded in broader policy initiatives that slow the rate of
      growth of health care spending and/or increase the income of the elderly.

PMID- 9926643
TI  - The political economy of Medicare.
AB  - Medicare spends more than $200 billion a year; the politics surrounding the
      Medicare program cannot be fully understood without an adequate appreciation of
      that fact. An understanding of the political economy of Medicare is perhaps best
      achieved by thinking along three dimensions: (1) Medicare as redistributive
      politics; (2) Medicare as special-interest politics; and (3) Medicare as
      distributive politics. Seeing the extent to which Medicare policies flow from
      these political processes makes clear that Medicare reform and broader political
      reform are, at some level, inseparable and indistinguishable.

PMID- 9926644
TI  - Budget bills and Medicare policy: the politics of the BBA.
AB  - With the Balanced Budget Act (BBA) of 1997 and a balanced federal budget, the
      link may be broken between the budget and Medicare policy's timing and direction.
      However, despite a balanced budget, Medicare's eventual financial crisis must be
      addressed. The BBAs of 1995 and 1997 provide two models of Medicare legislation:
      one based on conflict and another on consensus. Because the 1997 act became law
      and the 1995 act did not, the consensus model has proved to be politically
      feasible. However, this model appears to be inadequate for devising a solution to
      Medicare's long-term financial problems.

PMID- 9926645
TI  - Medicare reform: who pays and who benefits?
AB  - As Medicare's share of federal spending and gross domestic product (GDP) rises,
      the program may have increasingly important consequences not only for the health
      of Americans but also for their net income and financial well-being. We use
      incidence analysis to study payments and benefits in Medicare to various
      generations and income groups. We find that Medicare actually provides larger net
      dollar transfers to wealthier beneficiaries, although the "insurance value" of
      these dollars is greater for low-income households. We then evaluate a range of
      proposed Medicare reforms with regard to their impact on the distribution of both
      health care and disposable income.

PMID- 9926646
TI  - Uses and abuses of long-term Medicare cost estimates.
AB  - Long-term cost estimates are central to the current Medicare policy debate. This
      paper uses Congressional Budget Office (CBO) and Health Care Financing
      Administration (HCFA) data, and comparisons to international trends, to make some
      distinctions and warnings about the use of those estimates. Projected spending
      increases related to a larger enrollee population may be more easily justified
      than increases related to higher prices or volume of services per enrollee.
      Projections of demographics as if policy will not change are at least plausible;
      projections as if payment policies will not change for the next seventy-five
      years absurd. The demand for solutions that would "fix" the problem for seventy
      five years biases options in the direction of radical reforms, to the exclusion
      of more incremental and careful approaches.

PMID- 9926647
TI  - Three streams, one river: a coordinated approach to financing retirement.
AB  - A national retirement policy that coordinates Medicare, Social Security, and
      private pension reforms could make substantial progress in dealing with problems
      related to the baby-boom generation's retirement. Such a policy should include
      (1) better-designed work incentives for older persons--for example, a $10,000
      "retirement bonus" option, paid by Social Security and Medicare, for each year of
      delayed retirement; (2) allowing workers without employer-sponsored pensions to
      use Social Security's payroll contribution system to invest in pension accounts;
      (3) expansion of private long-term care insurance by allowing pension-plan assets
      to be used for paying premiums; and (4) placing a higher priority on financing
      for basic Medicare and Social Security benefits than on taxpayer-financed
      subsidies of far more generous pension benefits.

PMID- 9926648
TI  - Medicare: what's right? What's wrong? What's next?
AB  - Although future Medicare costs are highly uncertain, reasonable projections of
      those costs suggest a major financing problem. The Balanced Budget Act of 1997
      will provide temporary relief, although it introduced some new problems,
      including its geographic adjustment of Medicare+Choice rates. For the future we
      propose a premium-support system and an expanded benefits package. Such a system
      would provide a more flexible means to adjust the division of the financing
      burden between the elderly and the nonelderly, potentially gain some efficiencies
      from greater price competition and less reliance on administered pricing, and
      partly address the issue of uninsured early retirees.

PMID- 9926649
TI  - Will the care be there? Vulnerable beneficiaries and Medicare reform.
AB  - The Medicare program is on the verge of major change. The proof of the value of
      reforms will not rest in how well the program meets the needs of the healthy and
      wealthy, but rather in whether they preserve or improve upon protections for
      those who would not be well served by an unregulated private sector--persons with
      low incomes and/or substantial health problems. This paper examines four key
      issues: Which beneficiaries will likely be best served by a system oriented
      around choice; what role traditional Medicare should continue to play and what
      changes will be needed; what protections are necessary for persons with low and
      moderate incomes; and how these reforms could be incorporated into broader
      changes to make Medicare more viable over time.

PMID- 9926650
TI  - Restructuring Medicare for the next century: what will beneficiaries really need?
AB  - Medicare coverage falls short of its original mandate of access to modern
      medicine and protection against the high costs of medical care. These shortfalls
      destabilize both health outcomes and the economic viability of older adults and
      their families. Our proposed revisions would promote, rather than discourage,
      optimal care for beneficiaries. By replacing incentives for fragmented, episodic
      care with an orientation toward functional status, care management, and
      integration with long-term care, we can make an invaluable investment in a
      successfully aging society.

PMID- 9926651
TI  - Reexamining the delivery system as part of Medicare reform.
AB  - Medicare is more than a payment system. As the nation's largest public payer of
      health care, Medicare dictates the way health care is delivered to elderly and
      disabled persons. Health care and health outcomes cannot make substantial
      improvements until the delivery system is changed. Medicare reform must support a
      coordinated health care delivery system (in place of hospital-centered,
      fragmented care) and proactive chronic disease management (in place of episodic,
      reactive care). Consumers, government, community-based agencies, employers,
      health plans, and others need to develop a shared understanding of what outcomes
      we want to obtain, what delivery system reforms are required, and how financing
      can support those reforms.

PMID- 9926652
TI  - Bringing forth Medicare+Choice: HCFA's Robert A. Berenson. Interview by John K
      Iglehart.

PMID- 9926653
TI  - Medicare's Choice explosion? Implications for beneficiaries.
AB  - Medicare+Choice was established under the Balanced Budget Act of 1997 to expand
      the range of health plan options available to beneficiaries and to encourage
      plans to compete on the basis of price and quality, with potential savings to
      beneficiaries and the program. However, it is unclear whether the envisioned
      positive outcomes will occur. This paper reviews the rationale for expanding
      choices under Medicare. It considers how the rapidly changing health insurance
      market poses uncertainties for beneficiaries and concludes with a discussion of
      safeguards that may be necessary to assure that the program continues to work
      well for beneficiaries with diverse needs and circumstances.

PMID- 9926654
TI  - Medicare's end-stage renal disease program: current status and future prospects.
AB  - The twenty-five years of the end-stage renal disease (ESRD) program have been
      characterized by remarkable clinical achievements, which have prolonged and
      improved the quality of life for thousands of patients. As the program enters the
      next millennium, it faces considerable challenges: As the number and acuity of
      patients increase, the availability of trained nephrologists will decrease, and
      total costs will continue to rise. Policymakers will need to work closely with
      the renal professional and patient communities to develop creative approaches to
      delivering and financing ESRD care that is of the highest quality, yet is
      affordable.

PMID- 9926655
TI  - Public opinion, knowledge, and Medicare reform.
AB  - A review of public opinion and focus-group research reveals consistently
      inadequate understanding of Medicare by the public and misinterpretation of
      public opinion information by policy advocates. Closer analysis of apparent
      conflicts in values related to self-sufficiency, personal responsibility, and
      government, however, reveals strong support for the basic premises of social
      insurance embodied in Medicare. The likelihood of meaningful policy discussions
      about Medicare depends, in part, on whether the policy and research communities
      can find ways to provide the electorate with the knowledge they need to
      understand the implications of reform.

PMID- 9926656
TI  - Demographic issues in Medicare reform.
AB  - This paper estimates the contribution of demographics to the Medicare financing
      dilemma. It suggests that delayed eligibility, by itself, cannot solve this
      problem. Although there is uncertainty regarding each component of demographic
      change, there is little hope that the future population distribution will save
      the program without other, more painful, measures. Methods used in the private
      sector, such as prefunding, have not been seriously applied to medical insurance
      but might provide part of the solution for long-run solvency.

PMID- 9926657
TI  - Covering older Americans: forecast for the next decade.

PMID- 9926658
TI  - Trouble in the nurse labor market? Recent trends and future outlook.

PMID- 9926659
TI  - Reversal of fortune: commercial HMOs in the Medicaid market.
AB  - Between 1992 and 1996 the number of health maintenance organizations (HMOs)
      entering the Medicaid market grew at an average annual rate of approximately 22
      percent. Participation among all ownership segments grew, resulting in a broad
      distribution of beneficiaries across the HMO industry. However, recent declines
      in financial performance within the industry appear to be more dramatic for plans
      with many Medicaid members. In addition, growing concerns about rate adequacy and
      volatility as well as expanding administrative demands raise questions about the
      long-term commitment of commercial HMOs to Medicaid participation. This paper
      analyzes operating characteristics and financial performance of licensed
      commercial HMOs from 1992 through 1996, drawing on indepth interviews with health
      plan executives and managed care stock analysts.

PMID- 9926660
TI  - Prescription drug coverage, utilization, and spending among Medicare
      beneficiaries.
AB  - Outpatient prescription drugs are not a covered benefit under Medicare. There
      have been proposals in the past to expand Medicare benefits to include drug
      coverage, and current discussions dealing with "modernizing" the Medicare benefit
      package have raised the issue again. Using data from the 1995 Medicare Current
      Beneficiary Survey (MCBS), we describe the sources and extent of drug coverage
      among Medicare beneficiaries. The data show that 65 percent of Medicare
      beneficiaries have some level of drug coverage--a figure much higher than
      previous published numbers--and that 95 percent of Medicare health maintenance
      organization (HMO) enrollees have drug coverage. The data provide a baseline to
      observe future changes in the level of coverage, particularly among Medicare
      managed care plans.

PMID- 9926661
TI  - Impact of the BBA on Medicare HMO payments for rural areas.
AB  - The Balanced Budget Act (BBA) of 1997 radically changed the way Medicare risk
      plans are paid, replacing the adjusted average per capita cost (AAPCC) system
      with one in which county payment rates are set as the highest of (1) a
      local/national blended rate; (2) a national payment floor; or (3) a 2 percent
      minimum update from the prior year's rate. This DataWatch presents results of
      simulations of the likely impact of these changes throughout the BBA
      implementation period ending in 2003. The assessment considers urban/rural
      differences in payment levels, year-to-year rate volatility, the types of rates
      paid, and budget-neutrality issues.

PMID- 9926662
TI  - Medicare reform: foundations respond to federal policy changes.

PMID- 9926663
TI  - Health spending: questioning the assumptions.

PMID- 9926664
TI  - Functioning in a different health economy.

PMID- 9926665
TI  - Cost control: don't count employers out.

PMID- 9926666
TI  - Clinical significance of an extensor tendon anomaly to the little finger--a new
      finding.
AB  - A new anatomical variation of extensor digiti minimi (EDM) was discovered during
      our anatomical studies. The EDM usually gives one tendon to the little finger to
      extend the metacarpophalangeal joint (MPJ) independently from the other fingers.
      The EDM in our cadaver had three tendon slips. It supplied the MPJ of the little
      finger with two tendon slips. Along with the extensor digitorum communis (EDC),
      the EDM also had an additional slip to the ring finger MPJ extensor hood
      apparatus. The little finger also received a separate tendon from EDC.

PMID- 9926668
TI  - Age-related physiological alterations to muscles and joints and potential
      exercise interventions for their improvement.
AB  - This review article presents some general concepts related to the study of human
      aging that have specific implications for the maintenance or the development of
      improved muscular fitness in the elderly. Normal age-related alterations in
      muscle tissue, muscle function, and joint articulation, as well as possible
      mechanisms for these changes are presented and the current literature dealing
      with the use of exercise interventions to help stop or slow down the normal aging
      process is also summarized. Suggestions for basic evaluation and programming
      design are presented that address the needs of the older population.

PMID- 9926669
TI  - Intramuscular hemangioma: a benign tumor masquerading as malignant soft tissue
      tumor. Report of two cases.
AB  - We report two cases of intramuscular hemangiomas, one arising from the left flank
      region of a 33-year-old female, and another from the mid right back of a 25-year
      old man. In both cases the tumor masqueraded as malignancy and required a biopsy
      for correct diagnosis. Intramuscular hemangioma is a benign vascular tumor. Its
      tendency to deep location, infiltrative border, and fixity to surrounding tissues
      may cause it to be confused with malignant soft tissue tumors. Preoperative
      biopsy of the lesion is advised, and histopathologic examination is the only way
      to make a definitive diagnosis. Wide excision of the lesion is the treatment of
      choice. Follow up is required for any late recurrences.

PMID- 9926667
TI  - Preserved cognitive skills in dementia: implications for geriatric medicine.
AB  - Despite their severe and global cognitive impairments, some patients with
      Alzheimer's disease or vascular dementia continue to perform some complex mental
      activities skillfully. This paper briefly describes the artistic and game-playing
      skills of dementia patients, presents preliminary findings indicating that
      dementia patients with preserved skills exhibit slower cognitive deterioration
      than patients without retained cognitive skills, and illustrates how caregivers
      and other persons can utilize preserved abilities in the management of agitated
      and disruptive behavior.

PMID- 9926671
TI  - Oklahoma physician comments on "60 Minutes".

PMID- 9926670
TI  - 34-year-old man with history of progressive orthopnea and exertional dyspnea: a
      clinicopathological correlation conference from the University of Oklahoma
      College of Medicine.

PMID- 9926672
TI  - Congenital hypothyroidism screening in Oklahoma: a change in follow-up
      recommendations for 1999.
AB  - Effective January 1999, the Newborn Metabolic Disorder Screening Follow-up
      Program of the Oklahoma State Department of Health will no longer track
      hypothyroidism screen results of one abnormal T4 with normal TSH result. The
      Oklahoma State Department of Health Newborn Metabolic Disorder Screening Program
      (NMDSP) began screening for congenital hypothyroidism (CH) in 1979 and has
      subsequently identified 159 affected newborns. In 1997, Oklahoma had 46,740 live
      births, 51,431 specimens submitted to NMDSP Laboratory for screening, 1,302
      infants identified with an abnormal thyroid screen, and 11 infants diagnosed with
      CH with an average treatment age of 23.2 days (see Table 1). The NMDSP identifies
      an average of 14 CH cases each year. The pediatric health care provider can
      anticipate that in his/her practice, one out of 64 infants will be identified
      with an abnormal T4 with normal TSH result, and one out of 82 will be identified
      with an abnormal TSH value. In summary, one out of 36 infants will have some
      degree of abnormality on the thyroid screen.

PMID- 9926673
TI  - Strong performance improvement processes in health care organizations are at a
      monumental level.

PMID- 9926674
TI  - The performance measurement matrix: a framework to optimize decision making.
AB  - Patient care executives and performance improvement specialists continually are
      challenged to make decisions that have far-reaching effects on cost,
      productivity, and the quality of patient care. With multiple stakeholders to
      serve, minimal time to consider options, and an overabundance of data, new
      approaches to assessing and monitoring quality are needed. This article describes
      a framework and process to assist health care leaders in making informed and
      timely decisions. Six dimensions of health care--patients, caregivers, the
      organization, quality, efficiency, and cost--are assessed within the
      organization's context for overall impact on performance.

PMID- 9926675
TI  - Development and implementation of depression care along the health care
      continuum.
AB  - Depression is a common cause of illness with significant social, vocational, and
      economic consequences. As one of the most treatable forms of mental illness,
      depression often is underrecognized and undertreated. The annual cost of
      depression to the United States economy is approximately $43.7 billion, with 55
      percent (or $23.8 billion) accounting for missed work and lowered productivity.
      The prevalence rate of depression is estimated at 12-20 percent. The depressed
      patient utilizes two to three times more health services. There is little in the
      literature to demonstrate the care of the depressed person across the continuum
      in an integrated health care system. This article reviews the development and
      implementation of the treatment of depression care across multiple sites along
      the continuum. The care management depression team utilized the principles of
      performance improvement; Plan, Do, Check, Act framework for the initiative.

PMID- 9926676
TI  - Cultural competence: a priority for performance improvement action.
AB  - An increase in diversity that has been accompanied by a sharp decrease in white
      Caucasian "mainstream" culture has made cultural competence a priority in nursing
      performance improvement. Each culturally diverse group defines health and illness
      differently. Most have a long and well-established tradition of folk health
      beliefs and practices, which strongly impact members' reactions to American
      standards of care--an influence on both patient satisfaction and treatment
      compliance. This article describes the culture--health care relationship and
      lists 10 indicators for measuring cultural competency. It presents a practical,
      systemwide model for the improvement of nursing care quality through enhanced
      cultural competency and lists resources, which can be used to both support and
      improve cultural competency throughout an integrated health care system.

PMID- 9926677
TI  - Waterfalls and geysers: the development of diversity awareness at Children's
      Hospital.
AB  - The development of diversity awareness at Children's Hospital in Columbus, Ohio,
      has been a work in progress since the early 1980s. The interface of
      administration and individual initiatives ("waterfalls" and "geysers") has
      resulted in projects ranging from major international exchange programs to
      noontime Spanish language classes. This article recounts the journey from a
      parochial focus to a consciousness of multiculturalism in virtually all aspects
      of hospital interaction.

PMID- 9926678
TI  - Methodological issues in performance improvement in integrated systems.
AB  - This article presents an overview of processes necessary for effective
      performance improvement (PI) projects and includes a discussion of methodological
      issues that affect the quality of PI projects. Issues related to project design,
      project purpose, selection of a representative population for the project, and
      issues of sampling are presented. Data collection methods and instruments are
      analyzed and issues related to connecting the problem, the intervention, and the
      outcome are described. The final sections address strategies related to data
      analysis procedures and interpretation.

PMID- 9926679
TI  - Performance improvement integration: a whole systems approach.
AB  - Performance improvement integration in health care organizations is a challenge
      for health care leaders. Required for accreditation by the Joint Commission on
      Accreditation of Healthcare Organizations (Joint Commission), performance
      improvement (PI) can be designed as a sustainable model for performance to
      survive in a turbulent period. Central Baptist Hospital developed a model for PI
      that focused on strategy established by the leadership team, delineated
      responsibility through the organizational structure of shared governance, and
      accountability for outcomes evidenced through the organization's profitability.
      Such an approach integrated into the culture of the organization can produce
      positive financial margins, positive customer satisfaction, and commendations
      from the Joint Commission.

PMID- 9926680
TI  - Implementing outcome facilitation teams in an integrated system.
AB  - Coordination of patient care is the goal; the structure to promote the
      multidisciplinary plan of care is the unit-based outcome facilitation team. The
      focus of the team is the outcome achievement for the day, which could include
      patient education, therapies, or discharge planning.

PMID- 9926681
TI  - Affinity maps and relationship diagrams: two tools to enhance performance
      improvement.
AB  - This article describes two performance improvement tools: an affinity map and a
      relationship diagram. The author suggests when to use them and provides
      instructions on how to scan the environment of a nursing unit to discover
      problems, organize ideas about the problem, and find the root cause and effect of
      the relationship among staff's ideas about the problem. When the main cause and
      effect of a problem are known, management and staff can decide where to direct
      their process improvement efforts.

PMID- 9926683
TI  - Enthesitis, arthritis, and heel pain.
AB  - Often, individuals who present with "isolated" heel pain but with normal
      laboratory findings are dismissed without diagnosis. However, if these patients
      are carefully questioned and examined, a significant proportion are found to have
      a spondyloarthropathy. The keys to making this diagnosis are obtaining a thorough
      medical history and performing a complete physical examination. The classic
      complaints of back pain and enthesitis in other areas are frequently not reported
      by patients unless specifically sought, because they are thought to be unrelated
      to the heel pain.

PMID- 9926682
TI  - Evolution of the rearfoot. A model of adaptation with evidence from the fossil
      record.
AB  - The evolution of the human foot presents an obfuscation: explanations for its
      occurrence and the exact nature of mechanisms of change are still not fully
      understood. This article outlines a model of adaptation from a primitive ape foot
      and presents this as a hypothesis. Evidence substantiating the hypothesis is then
      presented, which explains many of the large-scale features distinctive to the
      human foot. Further evidence is then presented that goes some way toward
      explaining the sequence of modification with first the lateral side becoming
      adapted for terrestrial function followed by the medial side. Paradoxically, this
      was hypothesized by Morton more than half a century ago in his "hypothetical
      prehuman foot," though it was not accepted favorably at the time.

PMID- 9926684
TI  - Infectious causes of heel pain.
AB  - Heel pain is often attributed to a biomechanical etiology or sports-related
      injury. However, failure to recognize an infectious cause can lead to a delay in
      proper treatment and result in severe patient disability. This article reviews
      some of the more common infectious etiologies of heel pain.

PMID- 9926685
TI  - Problems and management of the rearfoot in neuromuscular disease. A report of ten
      cases.
AB  - Neuromuscular disease commonly affects the rearfoot as equinus, equinovarus, and
      equinovalgus deformity. Spastic hemiplegia caused by stroke, head injury, and
      cerebral palsy results in equinovarus deformity of the rearfoot. Spastic
      diplegia, most frequently caused by cerebral palsy, results in equinovalgus
      rearfoot deformity. Problems in ambulation, footwear, and bracing, as well as
      their orthopedic management, in patients with neuromuscular disease are discussed
      in a case-report format.

PMID- 9926686
TI  - Calcaneal gait. Etiology and clinical presentation.
AB  - Equinus deformities are common in neuromuscular and trauma patients. In contrast,
      calcaneal gait disorders tend to be overlooked, and few reports characterize and
      review calcaneal gait problems and disabilities. In the past 3 years, the authors
      treated 17 patients with calcaneal gait. Six of these cases are reviewed; in
      addition, the general clinical characteristics of the patient with calcaneal gait
      pattern are described.

PMID- 9926687
TI  - Total contact casts and removable cast walkers. Mitigation of plantar heel
      pressure.
AB  - The purpose of this study was to compare the ability of various modalities to
      reduce pressure in the plantar heel. Twenty-five patients with grade 1A plantar
      foot ulcerations were evaluated; a repeat measures design comparing plantar
      pressure was used to evaluate the total contact cast, the Aircast pneumatic
      walker, the DH pressure relief walker, and depth-inlay shoes. The total contact
      cast reduced pressure significantly better than the other modalities; however,
      its pressure reduction was only 33% less than a baseline sneaker. All other
      modalities reduced significantly more pressure than the depth-inlay shoe. The DH
      walker had a significantly lower pressure-time integral than other modalities.
      These data indicate that, while the total contact cast appears to be effective
      compared with other modalities, the role that limitation of transverse motion of
      the fat pad on compression at heel strike has yet to be fully explained.

PMID- 9926688
TI  - The complexities of HIV testing mount.

PMID- 9926689
TI  - Understanding juvenile violence: an Arkansas perspective.

PMID- 9926690
TI  - Systemic lupus erythematosus: a review of the cardiac manifestations.

PMID- 9926691
TI  - Radiological case of the month. Dural fistula.

PMID- 9926692
TI  - ECG of the month. To reason backward.

PMID- 9926693
TI  - Anomalies of the branchial apparatus.
AB  - Developmental abnormalities of the branchial apparatus represent a common cause
      of congenital lateral neck mass. Most often this is seen in the pediatric
      population but certainly may present at a much later age. The branchial apparatus
      contributes to major development of the head and neck, and a thorough
      understanding of embryology and anatomy is essential in treating these patients.
      Branchial anomalies may present as a cyst, sinus, or fistula; infection
      frequently complicates successful long-term management. Most often these lesions
      can be diagnosed by thorough history and physical examination. Complete surgical
      excision is the treatment of choice; however, recurrences may be encountered
      especially in those patients with a history of prior surgery or local infection.

PMID- 9926694
TI  - Radiology case of the month. Blastoma.

PMID- 9926695
TI  - The journal 150 & 100 years ago. Yellow fever.

PMID- 9926696
TI  - Protecting the public's health: action or cliches?

PMID- 9926697
TI  - Tuberculosis in Louisiana: an update.
AB  - The incidence of tuberculosis in the United States declined steadily until 1985
      when increases were seen, in part due to the AIDS epidemic. Although the decline
      resumed in 1992, tuberculosis remains a public health problem in Louisiana and
      nationally. In Louisiana in 1997, HIV infection was present in 14% of persons
      with tuberculosis whose HIV status was known. In that year there were 16 cases of
      tuberculosis that were resistant to at least one first-line anti-tuberculous
      drug. Infection with Mycobacterium tuberculosis is diagnosed with the tuberculin
      skin test; the size of induration considered positive varies with the risk status
      of the person tested. TB infection in immunocompetent persons under age 35 is
      treated with 6 months of isoniazid. TB disease is generally treated with 4 drugs
      until antimicrobial sensitivities are known. Directly observed therapy is an
      inexpensive way to ensure compliance and is routinely used for patients in
      Louisiana.

PMID- 9926699
TI  - Pediatric tuberculosis: problems in diagnosis and issues in management.
AB  - The diagnosis of infection and disease due to Mycobacterium tuberculosis in
      infants and children presents many clinical challenges. The distinction of
      infection from disease (tuberculosis) in children is often unclear. There is
      difficulty in obtaining positive microbiological confirmation of infection in
      sputum, gastric, tracheal, or bronchial aspirates and in other body fluids in
      infants and children. Isoniazid is effective in the treatment of infection and
      prevention of progression of infection to clinical disease. Approximately 50% of
      children with primary tuberculosis are asymptomatic and are diagnosed as a result
      of contact investigation. Children become infected from exposure to an adult or
      adolescent with contagious pulmonary tuberculosis. The results of drug
      susceptibility tests in the source case in contact with an exposed child can
      guide the antituberculous chemotherapy. Chemotherapy regimens for treatment of
      pediatric tuberculosis have become shorter and more intensive with a marked
      increase in directly observed therapy (DOT).

PMID- 9926698
TI  - Pharmacotherapy of chronic obstructive pulmonary disease.
AB  - Despite a significant reduction in cigarette consumption, chronic obstructive
      pulmonary disease continues to be an important cause of mortality in the United
      States. COPD is characterized by progressive airflow obstruction which is
      punctuated by acute exacerbations. Nicotine substitution and use of bupropion
      have been shown to double long-term smoking cessation success. The combination of
      albuterol and ipratropium bromide produces a synergistic beneficial effect on
      pulmonary function and symptoms. Long-acting inhaled beta 2-agonists improve
      symptoms better than as needed albuterol. Oral corticosteroids appear to be
      helpful during acute exacerbations; however, the chronic use of steroids benefits
      only a minority of patients. Broad- spectrum antibiotics are indicated during
      acute exacerbations if there is increased sputum volume and purulence. System
      oriented administration of pneumococcal and influenza vaccinations is more
      successful than provider or client-oriented approaches.

PMID- 9926700
TI  - Diagnosis and management of asthma: a summary of the National Asthma Education
      and Prevention Program guidelines. National Institutes of Health.
AB  - Asthma is a common disease that affects persons of all ages. It is responsible
      for more than 5,000 deaths annually in the United States and countless days
      absent from school and work. For these reasons, the National Institutes of Health
      established the National Asthma Education Program whose expert panels have
      published two reports: Guidelines for the Diagnosis and Management of Asthma in
      1991 and a revised report in 1997. A summary of the Expert Panel Report 2
      published in 1997 is presented with emphasis on the outpatient diagnosis,
      prevention, and treatment of asthma. Education of the clinician and the patient
      is essential for effective management of asthma, and effective communication
      between clinician and patient is essential for implementing asthma education. The
      goal of this summary is to communicate and disperse the asthma education provided
      by the Guidelines for the Diagnosis and Management of Asthma: Expert Panel Report
      2 in hopes of improving asthma care and decreasing morbidity and mortality
      attributed asthma.

PMID- 9926701
TI  - Pulmonary pearls. Lymphocytic interstitial pneumonitis.

PMID- 9926703
TI  - Acute management of airway compromise in cancer.
AB  - Major airway obstruction is a frightening complication of thoracic tumors.
      Patient presentation may be abrupt. They may experience profound dyspnea, post
      obstructive pneumonia, respiratory failure, or progress to death. Immediate
      relief of obstruction can be accomplished by bronchoscopy with laser or stenting
      in most patients. Such interventions can improve the quality of life and
      longevity of these patients and must be considered in the initial treatment of
      patients with airway obstruction.

PMID- 9926702
TI  - Pulmonary pearls. Allergic bronchopulmonary aspergillosis.

PMID- 9926705
TI  - Cryptococcus neoformans.

PMID- 9926704
TI  - New therapies for cystic fibrosis.
AB  - In the decade since the gene responsible for cystic fibrosis (CF) was identified,
      our understanding of the pathophysiology of CF pulmonary disease has
      significantly improved. The current model for CF lung disease suggests several
      levels at which clinical interventions may be made in an attempt to alter the
      natural course of disease progression. The first part of this review highlights
      some of the progress made in novel forms of therapy directed at earlier portions
      of the pathophysiologic cascade such as gene therapy, protein therapy, and ion
      transport regulatory therapy. New developments in well-established modes of
      therapy such as mucolytic therapy, airway clearance therapy, and antibiotic
      therapy are discussed next. The review concludes with a look at the use of two
      forms of therapy that have been adapted to CF care, anti-inflammatory therapy and
      lung transplantation.

PMID- 9926706
TI  - Eosinophilic granuloma.

PMID- 9926707
TI  - Hamman-Rich syndrome.

PMID- 9926708
TI  - [What should we truthfully tell the cancer patient?].

PMID- 9926709
TI  - [Fernand-Widal hospital. Origins and avatars].

PMID- 9926710
TI  - [Introduction. Diabetes type 2].

PMID- 9926711
TI  - [Diagnostic criteria for type 2 diabetes].
AB  - A new definition of diabetes is just about to be adopted by WHO. The main change
      concerns the glycemic threshold for diagnosis of diabetes. Its value will
      decrease from 7.7 mmol/L to 7 mmol/L. This drop is neither the consequence of a
      methodological change (diabetes remains defined by glycemic values at risk of
      retinopathy) nor a revision of the gold standard (glycemic value > or = 11 mmol/L
      at 2 h. post glucose load remains the most accurate criterion for diagnosis). The
      only purpose of the new definition is to better correlate fasting glycemia with
      the 2 h. post load value during OGTT. So, the new definition of diabetes with a
      glycemic value > or = 7 mmol/L will allow to do diagnosis without OGTT. The WHO
      experts hope that this simplification will improve the earliness of diagnosis and
      treatment. WHO will propose to categorize 3 groups according to glycemic values:
      normal values < 6.05 mmol/L, diabetic values > 7 mmol/L, and impaired fasting
      glucose encompassing values above normal but below the diagnosis cut-off for
      diabetes (plasma glucose > or = 6.05 mmol/L to < 7.0 mmol/L). This impaired
      fasting glucose should be considered as a risk factor for diabetes and
      cardiovascular disease.

PMID- 9926712
TI  - [Physiopathological fundamentals of type 2 diabetes].
AB  - Type 2 diabetes is characterized by 2 major defects: 1. a dysregulation of
      pancreatic hormone secretion (quantitative and qualitative (early phase,
      pulsatility) decrease of insulin secretion, increase in glucagon secretion); 2. a
      decrease in insulin action on target tissues (insulin resistance). The defects in
      insulin action on target tissues are characterized by a decreased in muscle
      glucose uptake and by an increased hepatic glucose production. These
      abnormalities are linked to several defects in insulin signaling mechanisms and
      in several steps regulating glucose metabolism (transport, key enzymes of
      glycogen synthesis or of mitochondrial oxidation). These postreceptors defects
      are amplified by the presence of high circulating concentrations of free fatty
      acids in obese diabetic subjects (Randle cycle). The increased hepatic glucose
      production is due to a stimulation of gluconeogenesis secondarily to the enhanced
      glucagon secretion and to the presence of high circulating concentrations of free
      fatty acids in obese diabetic subjects (provision of obligatory cofactors such as
      acetyl-CoA).

PMID- 9926713
TI  - [Surveillance of uncomplicated type 2 diabetes].
AB  - Follow up in type 2 diabetes must be regular with an annual check-up and
      pluriannual consultations of adapted frequency. It's important to consider the
      diabetic patient in totality: reaching the previous objectives of weight and
      glycaemia, all vascular risk factors and evolution to complications. Some tests
      are necessary (retin exam, microalbuminuria, ECG...), but with an attentive
      clinic exam we can avoid many useless and expensive paraclinic explorations. It's
      also a motivation tool for patients.

PMID- 9926714
TI  - [Coronary disease and type 2 diabetes].
AB  - Coronary heart disease is the leading cause of premature deaths in type 2
      diabetic patients. Atypical in its clinical presentation or silent coronary heart
      disease in this population is to be detected early in those patients at high risk
      of cardiovascular disease. Males with peripheral artery disease, albuminuria and
      those with (or) the combination of tobacco use, hypertension and dyslipidemias.
      Exercise test is the non-invasive investigation to be used as a first line
      examination. A coronary angiography is to be performed in the patients with a
      positive exercise test. A significant stenosis of the left main coronary artery
      or a triple vessel disease, common conditions in diabetic patients, should lead
      to myocardial revascularisation which reduces cardiovascular mortality and
      morbidity. The diagnosis of coronary heart disease in type 2 diabetic patients,
      should induce in all cases a medical treatment including cardiological and
      metabolic therapies, unfortunately very poorly performed in too many patients.

PMID- 9926715
TI  - [Diet and fitness in type 2 diabetes].
AB  - Fitness and dietary measures remain the corner stone of the treatment of type 2
      diabetic patients. The two objectives of these measures are: (i) to improve the
      glycemic control and to normalize the biological abnormalities which are
      frequently associated with the diabetic state; (ii) to prevent the micro and
      macrovascular complications. All these measures should be simplified, and
      sufficiently attractive to be acceptable and accepted by the patient. Weight-loss
      objectives in overweight diabetic patients should remain within reasonable
      limits: a few kilogram- loss is sufficient in many cases. In order to maintain
      the palatability of the diet, the dietary fat intake must be set at sufficient
      high levels, just by adjusting the carbohydrates/monounsaturates fat balance.
      When physical training is recommended, this activity must appear as a leisure and
      not as a constraint. More generally the management plan should be multifactorial
      and avoid contradictory measures.

PMID- 9926716
TI  - [Oral antidiabetic drugs].
AB  - Type II diabetes includes various pathophysiologic entities. Glycoregulatory
      disorders are due to multiple mechanisms, associated to different degrees.
      Identical response to treatment is not observed among patients or at different
      times of treatment, early or later in the disease. Until very recently, the
      treatment available was insufficient. It now has gained new classes of drugs that
      act on the secretion of insulin, the sensitivity to insulin and the rate of
      intestinal glucide absorption. Approaches to treatment are often complementary
      and oral antidiabetic drugs can be associated. Hygienic and dietary measures
      remain indispensable to reinforce drug efficacity and to prevent complications in
      these patients.

PMID- 9926717
TI  - [Insulin in the treatment of type 2 diabetes].
AB  - Insulin use in NIDDM is a frequent situation. Many acute clinical circumstances
      justify a transient insulin therapy including ketoacidosis decompensation or
      hyperosmolar state and severe intercurrent diseases. The problem is more complex
      when glycemic control is no longer obtained despite maximal doses of oral
      treatment. Type 2 diabetes is then defined as an insulin-requiring diabetes.
      There is actually no consensus, but lots of arguments advocate an intensive
      insulin therapy based on multiple daily injections in this clinical state.
      However, when patient's overweight is important or if the clinical context is
      unfavourable, conventional insulin therapy or combined treatment using bedtime
      insulin and daytime oral agents may be tried.

PMID- 9926718
TI  - [Therapeutic decisions in type 2 diabetes].
AB  - Evidence-based therapeutic decisions in type 2 diabetes are considered here in
      terms of both the individual and public health policy. They lead to the
      recommendation which has proved to be the most effective: early, intensive,
      global care, first for glycemic control, then, according to the case, for the
      other risk factors of atheromatosis.

PMID- 9926719
TI  - [Tobacco, students, education and health].

PMID- 9926720
TI  - [Colonic diverticulosis. Epidemiology, diagnosis, disease progression, principles
      of treatment].

PMID- 9926721
TI  - [Endometrial cancers. Epidemiology, diagnosis, disease progression and principles
      of treatment].

PMID- 9926722
TI  - [Malaria. Epidemiology, etiology, physiopathology, diagnosis, disease
      progression, treatment and principles of individual prevention].

PMID- 9926723
TI  - [Infectious diseases during pregnancy. Prevention, diagnosis and fetal risks].

PMID- 9926724
TI  - [Elective abortion. Legislation, epidemiology, complications].

PMID- 9926726
TI  - The physician's role in organ donation and the collaborative approach to
      potential donor families.

PMID- 9926725
TI  - The continuing struggle to eliminate hemolytic disease of the newborn from RH (D)

PMID- 9926727
TI  - State of South Dakota's child: 1998.
AB  - Births in South Dakota again decreased in 1997, continuing an ongoing trend that
      began in 1980. Progress in 1997 was noted in the use of first trimester prenatal
      care and the rate of low birth weight in the State remained lower than that
      observed nationally. The State's infant mortality rate for 1997 showed a
      continuation of the favorable shift in rates of the last decade that was
      initiated with the progress observed in 1996. Smoking and drinking during
      pregnancy is higher in South Dakota than noted nationally. How and why substance
      abuse prevention efforts must begin during childhood is discussed in this review.
      Currently, the rates of smoking and alcohol use are higher among South Dakota
      teens than noted nationally, and have increased over the past six years.
      Approaches to preventing substance abuse for the sake of the health and well
      being of youth and their potential future children are presented.

PMID- 9926728
TI  - New vaccines.

PMID- 9926729
TI  - The Federation of State Medical Boards of The United States, Inc. Model
      guidelines for the use of controlled substances for the treatment of pain.

PMID- 9926730
TI  - Simultaneous pancreas-kidney transplantation: an overview of indications,
      complications, and outcomes.
AB  - Simultaneous pancreas-kidney transplantation (SPK) has become an accepted therapy
      for the treatment of patients with insulin-dependent diabetes mellitus and renal
      failure from diabetic nephropathy. The procedure has evolved over the last twenty
      years, and refinements in technique, better organ preservation solutions, and
      more potent immunosuppressive therapies have improved one-year graft-survival
      rates to 81% for the pancreas and 88% for the kidney (International Pancreas
      Transplant Registry Data-1996). Proper patient selection is important, given the
      increased complexity of the procedure, the increased need for immunosuppression,
      and the need for compliance with postoperative medications and monitoring. The
      benefits of a successful SPK include more physiologic glucose metabolism and
      freedom from dialysis. This review will describe the indications and selection
      process for potential candidates, outline the procedure and postoperative care,
      and discuss the potential impact on secondary complications of diabetes mellitus.
      It will then discuss results and complications from the use of current protocols
      and immunosuppression at the University of California at San Francisco.

PMID- 9926731
TI  - Research interests of physicians in two practice-based primary care research
      networks.
AB  - Regional practice-based network research has grown significantly in the past 15
      years. Previous studies have reported on characteristics of physicians who
      participate in network research, but little is known about the specific a priori
      research interests of practicing physicians. Knowledge of such interests could be
      useful in planning network research studies. We conducted a mail survey to assess
      the research interests of primary care physicians in two contiguous research
      networks at the University of California at San Francisco (UCSF) and at Stanford
      University. Among 120 respondents from the UCSF Collaborative Research Network
      and 85 from the Stanford Ambulatory Research Network, the most common topics of
      interest were disease prevention, communication and compliance, and managed care.
      Among specific conditions, heart disease, hypertension, and respiratory infection
      were of interest to the majority of respondents. Topics not of interest to
      network members were obstetrics, diagnostic procedures, alcoholism, drug abuse,
      tuberculosis, male genito-urinary problems, occupational hazards, domestic
      violence, and AIDS and HIV. Identification of network physician research
      interests can help focus research and recruitment efforts on topics of interest
      and provide estimates of participation levels for planning studies and preparing
      funding applications for research networks.

PMID- 9926732
TI  - Relationship between earlier and later mammography screening--California
      Medicare, 1992 through 1994.
AB  - Regular screening mammography is recommended to reduce breast cancer mortality.
      Although predictors of mammography have been studied, factors that influence
      adherence to guidelines are less understood. We examined the relationship between
      an index mammogram and subsequent mammograms among California Medicare
      beneficiaries. Medicare billing data for 1992, 1993, and 1994 were used to
      estimate the association between screening mammography in 1992 and subsequent
      screening in 1993 or 1994. We found that women with a 1992 mammogram were more
      than twice as likely to have a mammogram in 1993 or 1994 than women without a
      1992 mammogram (relative risk = 2.58; 95% confidence interval, 2.57-2.59). This
      relationship was somewhat stronger for black women compared with white women and
      increased with age. Although further study of regular screening patterns is
      needed, these findings provide some evidence that encouraging a single mammogram
      may lead to continued adherence.

PMID- 9926733
TI  - Mental illness in elementary-school-aged children.
AB  - We conducted a retrospective analysis of 1992 hospital discharge data to
      determine the incidence of mental illness hospitalizations among elementary
      school-aged children and to analyze differences in hospital use by selected
      population characteristics. We analyzed population-based records of
      hospitalizations of 6- to 12-year-olds (n = 4,460) with a principal diagnosis of
      mental illness and calculated relative risks (RRs) for hospitalization by sex,
      race/ethnicity, and payment source. Mental illnesses accounted for 8.1% of
      hospitalizations and 28.9% of hospital days for 6- to 12-year-olds. Hospital
      charges totaled $85 million. Boys had a higher risk of mental illness
      hospitalization than girls (RR 1.96; 95% confidence interval [CI] 1.84-2.08).
      Latino children had a lower risk than whites (RR 0.22; 95% CI 0.20-0.24), as did
      children in the "Asian/other" group (RR 0.12, 95% CI 0.10-0.15). Inpatient
      hospitalizations for mental illness have a major impact on hospital morbidity for
      elementary-school-age children. Boys are overrepresented and Latinos and
      Asians/others are underrepresented among mental illness hospitalizations.
      Clinical implications for these findings and barriers to the delivery of
      inpatient mental health care are discussed.

PMID- 9926734
TI  - Internal medical residents' ability to diagnose and characterize major
      depression.
AB  - The purpose of this study was to assess medical residents' knowledge of symptom
      criteria and subtypes of major depressive episode and their accuracy in
      diagnosing major depressive disorders and classifying episode severity and
      subtype according to criteria of the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition. Thirty-five third-year internal medicine residents
      completed a self-administered, written instrument containing 2 open-ended
      questions and 21 hypothetical scenarios. The sensitivity for recognizing major
      depressive disorder was 64%, and the specificity was 69%. The sensitivity for
      classifying severity was 86% for mild, 66% for moderate, 71% for severe, and 66%
      for severe with psychosis. Misclassification of severity was most commonly to a
      less severe class. For scenarios with a diagnosable subtype of a major depressive
      disorder, the sensitivity for classification was 34% for atypical, 51% for
      catatonic, 74% for melancholic, 100% for postpartum, and 94% for seasonal
      depression. When asked to enumerate the criteria symptoms for depression, 80% or
      more of the residents listed sad mood, loss of interest, weight change, and sleep
      disturbances; 14 to 21 (40%-60%) listed thoughts of death and worthlessness;
      other criteria were listed by 7 to 11 (20%-31%). When asked to list the episode
      subtypes, none was listed by more than 3 (9%) residents, although 13 (37%)
      residents volunteered psychotic as a subtype. Residents frequently failed to
      recognize the presence or absence of major depressive disorder and often
      misclassified episode severity and subtype on scenarios. Few could spontaneously
      list the episode subtypes. Methods must be developed to improve the recognition
      and classification of major depressive episodes to better direct treatment.

PMID- 9926735
TI  - Nonsurgical causes of pneumoperitoneum.
AB  - The radiographic manifestation of free air in the peritoneal cavity suggests
      serious intra-abdominal disease and the need for urgent surgical management. Yet,
      about 10% of all cases of pneumoperitoneum are caused by physiologic processes
      that do not require surgical management. We retrospectively reviewed cases of
      nonsurgical causes of pneumoperitoneum at the 2 teaching hospitals of a
      university medical center between January 1990 and December 1995. Successful
      management by observation and supportive care without surgical intervention was
      defined as the diagnostic feature of nonperforation. Failure of a laparotomy to
      delineate a surgical cause or to result in a reparative procedure is congruent
      with a nonsurgical cause of pneumoperitoneum. During this period, 8 patients (6
      men and 2 women; mean age, 61 years) were identified with nonsurgical causes of
      pneumoperitoneum. Two patients underwent negative laparotomy, and the other 6
      were successfully managed nonoperatively and discharged from the hospital. In 6
      patients, a cause of the pneumoperitoneum was identified. The causes may be
      grouped under the following categories: postoperatively retained air, thoracic,
      abdominal, gynecologic, and idiopathic. In our review of the literature, 61 of
      139 reported cases underwent surgical treatment without evidence of perforated
      viscus. To avoid unnecessary surgical procedures, both primary medicine
      physicians and surgeons need to recognize nonsurgical causes of pneumoperitoneum.
      Conservative management is warranted in the absence of symptoms and signs of
      peritonitis.

PMID- 9926736
TI  - Cocaine-induced intestinal ischemia.

PMID- 9926737
TI  - Potentiation of warfarin sodium by amiodarone-induced thyrotoxicosis.

PMID- 9926738
TI  - Persistent hiccups induced by dexamethasone.

PMID- 9926739
TI  - Ticarcillin/clavulanate versus imipenem/cilistatin for the treatment of
      infections associated with gangrenous and perforated appendicitis.
AB  - The objective of this study was to compare ticarcillin/clavulanate given at 3.1 g
      every 6 hours with imipenem/cilistatin given at 500 mg every 6 hours for the
      treatment of infections associated with gangrenous or perforated appendicitis.
      One hundred thirty-seven patients were found to have gangrenous or perforated
      appendicitis and received the study medication for 3 to 5 days in a double
      blinded, randomized manner. Clinical success was similar for the two treatment
      groups, 96.9 and 95.9 per cent in the ticarcillin/clavulanate and
      imipenem/cilistatin groups, respectively (P=0.99; 95% confidence interval for the
      difference was -5.6% to 7.6%). Bacteriologic success at the end of therapy was
      similar in the two groups, 100 and 98.4 per cent in the ticarcillin/clavulanate
      and imipenem/ cilistatin groups, respectively (P=0.99; 95% confidence interval
      for the difference was -1.8% to 4.7%). The occurrence of adverse events related
      to treatment was similar for the two groups (P=0.31) and led to study withdrawal
      for four patients (one with ticarcillin/clavulanate and three with imipenem/
      cilistatin). Ticarcillin/clavulanate given at 3.1 g every 6 hours is as effective
      and as safe as imipenem/ cilistatin given at 500 mg every 6 hours for treatment
      of gangrenous or perforated appendicitis.

PMID- 9926740
TI  - Are pancreatic tumors hormone dependent?: A case report of unusual, rapidly
      growing pancreatic tumor during pregnancy, its possible relationship to female
      sex hormones, and review of the literature.
AB  - The occurrence of a pancreatic tumor in a young patient is rare. However, when
      one identifies a pancreatic mass during pregnancy and particularly when the
      lesion is located in the tail of the pancreas, "unusual tumors" of the pancreas
      should be considered. The management of these tumors during pregnancy presents
      unusual challenges because of rapid tumor growth probably related to elevated
      levels of sex hormones. An immunohistochemical study was done to evaluate for
      hormone receptors of the tissue removed from the tumor. We present a case of a 37
      year-old female patient in her 4th week of pregnancy who was found to have a
      pancreatic mass; she was followed with ultrasonography. At the 23rd week of
      gestation, the tumor increased in size to more than 12 cm and required resection.
      Immunohistochemical studies were done to evaluate receptors for progesterone,
      estrogen, PS2-estrogen-related protein, pancreatic polypeptide antigen, flow
      cytometry, DNA ploidy, and proliferative activity in tumor cells. Pathology
      showed a low-grade multiloculated mucinous cystic neoplasm of the pancreas. There
      was a positivity for progesterone receptor and PS2-estrogen-related protein but
      not for estrogen receptor in the tumor. We conclude that a pancreatic mass
      detected during pregnancy requires a different consideration for its management.
      Early tissue diagnosis with CT or ultrasound-guided biopsy is essential. Even
      those lesions diagnosed as benign would require early intervention because of
      their rapid growth, probably influenced by female sex hormones.

PMID- 9926741
TI  - Presacral cysts: transrectal excision in select patients.
AB  - Fourteen patients presenting with presacral cystic lesions were managed over a 20
      year period. Retrospective review identified 12 females and 2 males. Fifty-seven
      per cent were symptomatic at diagnosis. Forty-three per cent presented with pain;
      half of these patients had infected cysts. All lesions were palpable on digital
      rectal exam. Computed tomography identified the cyst in all seven patients in
      which it was performed. The transrectal approach was used for cyst excision in
      ten patients. One patient had transrectal drainage and wall biopsy only. Three
      patients underwent posterior parasacral excision. Pathologic review demonstrated
      four dermoid cysts, four epidermoid cysts, four cyst hamartomas, and two benign
      teratomas. One cyst hamartoma had a focus of invasive adenocarcinoma. Two
      complications occurred. There were no deaths. Follow-up averaged 39 months, at
      which time there were no recurrences. Developmental cysts are the most common
      presacral tumors. Excision is recommended, and the transrectal approach may be
      used in select patients with low morbidity and minimal recurrence.

PMID- 9926742
TI  - The natural history of extremity venous repair performed for trauma.
AB  - Surgical repair of extremity venous injuries remains controversial. Literature
      supports both ligation and repair when analyzed for functional recovery. However,
      few studies review the natural history of venous repair for trauma. Twenty
      patients were prospectively enrolled in a protocol of immediate repair of major
      extremity veins. Simple venorraphy and complex reconstructions were performed at
      the discretion of the operative team. Patients were studied by contrast venogram
      on postoperative day 3 and 6 weeks after surgery. Patients with occluded repairs
      at 3 days received a 5-day course of intravenous anticoagulation and were
      discharged. Overall, patency at 3 days was 55 per cent and increased to 88 per
      cent at 6 weeks (P < 0.02). Lateral venorraphy and direct reapproximation had
      higher patency rates than complex repairs at 6 weeks (92% versus 50%; P < 0.05).
      All veins that were patent at 3 days remained patent (correlation coefficient
      1.0). Repair of traumatized extremity veins carries minimal morbidity and has a
      high rate of early and eventual patency. Long-term anticoagulation in the face of
      early thrombosis is unnecessary.

PMID- 9926743
TI  - Recurrent acute pancreatitis caused by a gastric duplication communicating with
      an aberrant pancreas.
AB  - A 24-year-old female patient who had suffered from recurrent bouts of acute
      pancreatitis for over 3 years was found on endoscopic retrograde
      cholangiopancreatography to have an aberrant pancreatic duct that terminated in a
      cyst. An aberrant lobe of pancreas had been discovered at exploratory laparotomy
      3 years previously and was left untreated. Excision of the aberrant lobe of
      pancreas and accompanying gastric duplication cyst was curative. This case
      illustrates the importance of obtaining endoscopic retrograde
      cholangiopancreatography in all young individuals with recurrent pancreatitis to
      detect this rare, but curable, cause of pancreatitis.

PMID- 9926744
TI  - A reevaluation of the radiographically detectable complications of percutaneous
      venous access lines inserted by four subcutaneous approaches.
AB  - As a result of prior studies elucidating the potential complications associated
      with the use of central venous access lines, the Food and Drug Administration and
      the manufacturers themselves have published guidelines and warnings outlining
      these dangers and describing the safest insertion techniques. We will attempt to
      determine whether this improved education has altered the number and type of
      complications, comparing the results from different types of hospitals, among the
      various medical services and among operators with varying degrees of experience.
      This is a prospective analysis of all central venous pressure (CVP) and Swanz
      Ganz catheters (SGCs) inserted between July 1, 1995, and February 30, 1996, at a
      regional Veteran's Affairs hospital and an inner city university medical center.
      Three hundred seventy-five inpatients underwent 417 new percutaneous venous
      catheter placements while in the medical or surgical intensive care units or in
      the general care wards. A portable chest radiograph was obtained immediately
      after each procedure, and the position of the catheter and any associated
      complications were recorded, initially by the radiology resident in the emergency
      suite and subsequently as confirmed by a chest radiology attending. CVP lines
      were considered malpositioned when the tip was not located in the superior vena
      cava, and SGCs were recorded as misplaced when the tip was not found within the
      main, left main, right main, or either lower lobe pulmonary artery within 2 cm of
      the cardiac border. For patients undergoing CVP line placement, the right atrium
      was the most frequent site of tip malposition with 38 of 69 total misplacements
      (55%), whereas for SGCs, 22 of 55 malplacements (40%) were too distal in a lower
      lobe pulmonary artery. Only 1 of 248 CVP lines resulted in a pneumothorax (PTX;
      0.4%), whereas 6 of 169 SGC insertions caused a PTX (3.5%), a significant
      difference (P=0.019). Five of 192 catheters (2.6%) placed via an internal jugular
      approach resulted in PTX, whereas only 2 of 150 subclavian cannulations (1.3%)
      caused this complication, revealing a trend, but not reaching statistical
      significance (P=0.473). However, there was a significant decrease in the rate of
      catheter misplacements in the third part of the month compared with the first 20
      days (35% versus 24%; P=0.031), and the Veteran's Affairs hospital displayed a
      trend toward more complications for SGC insertions than the university hospital
      (47% versus 32%), but not for CVP lines. In general, individual medical and
      surgical services displayed a similar frequency of complications (29-38%), except
      for CVP lines inserted in the medical intensive care unit. Venous access catheter
      tip malpositions are very common in all settings, but easily recognized by
      radiography, whereas PTXs are unusual. In contrast to most older studies, PTXs
      are more frequently observed with internal jugular as opposed to subclavian
      cannulations and with SGCs rather than CVP lines. However, our data support prior
      studies that the right atrium and distal right lower lobe pulmonary artery are
      the most common sites for CVP and SGC misplacement, respectively, and that there
      is an improvement in success rates with increasing operator experience.

PMID- 9926745
TI  - Tuberculoma of the spleen: a rare but important clinical entity.
AB  - Tuberculoma of the spleen has been an extremely rare entity during the last
      decades in the Western world. We describe a case in a young, HIV-negative woman
      who was evaluated for fever of unknown origin. The workup was initially negative,
      and she was treated successfully with steroids and nonsteroidal anti-inflammatory
      analgesics. Recurrence of the fever and an abnormal CT of the abdomen lead to an
      exploratory laparotomy, which revealed a subcapsular caseous material containing
      splenic abscess. The very few cases reported in the literature, and the
      increasing incidence of extrapulmonary tuberculosis due to the alarming numbers
      of immunodeficient patients that a surgeon may encounter are also discussed.

PMID- 9926746
TI  - Transection of the base of the tongue caused by penetrating injury.
AB  - Traumatic transection of the base of the tongue can be a life-threatening injury
      because of blood loss and airway obstruction. Airway control, hemostasis, and
      meticulous anatomic repair are necessary to prevent speech and airway
      dysfunction. Laryngeal injuries, when present, require these same principles.

PMID- 9926747
TI  - Choledocholithiasis: endoscopic versus laparoscopic management.
AB  - Choledocholithiasis is present in 6 to 10 per cent of patients who have
      cholelithiasis. In the era of laparoscopic cholecystectomy, endoscopic retrograde
      cholangiopancreatography with endoscopic retrograde sphincterotomy (ERCP/ERS) and
      laparoscopic common bile duct exploration (LSCBDE) have been used to treat
      choledocholithiasis. The purpose of this study is to compare ERCP/ERS with
      LSCBDE. A retrospective review of 913 patients undergoing laparoscopic
      cholecystectomy identified 61 patients who had ERCP/ERS or LSCBDE to treat
      choledocholithiasis at a community medical center between 1990 and 1996. Outcome
      parameters were hospital length of stay (LOS), hospital cost, and complications.
      The results were: ERCP (n=26; LOS, 5.0+/-3.6 days; cost, $11,823+/-$7,000;
      complications, 23.1%); LSCBDE (n=35; LOS, 3.4+/-2.4 days; cost, $9,100+/-$2,884;
      complications, 2.9%); and P value (LOS, 0.028; cost, 0.066; complications,
      0.034). LSCBDE results in a significantly shorter LOS and significantly fewer
      complications, and is less costly than ERCP/ERS. LSCBDE, when feasible, should be
      considered the gold standard for the management of choledocholithiasis.

PMID- 9926748
TI  - Primary aortojejunal fistula: a case report.
AB  - Primary aortoenteric fistulae (AEFs) are extremely rare vascular entities, with
      fewer than 250 cases reported in the world medical literature as of 1996.
      Incidence is less than 1 per cent, with a mortality ranging from 33 to 85 per
      cent. Atherosclerosis remains the most common etiology, accounting for more than
      two-thirds of the cases reported. Other etiologies include carcinoma, ulcers,
      gallstones, diverticulitis, appendicitis, and foreign bodies. Early diagnosis is
      crucial for survival and mandates recognition of the typical "herald bleed."
      Additional findings on initial presentation frequently include flank pain,
      abdominal pain, hematemesis, melena, and an abdominal mass. More than 80 per cent
      of primary AEFs involve the duodenum, with the overwhelming majority located in
      the third or fourth portion. Successful management of primary AEF requires a high
      index of suspicion for diagnosis and prompt surgical intervention for survival.

PMID- 9926749
TI  - Preferred route of tracheostomy--percutaneous versus open at the bedside: a
      randomized, prospective study in the surgical intensive care unit.
AB  - Percutaneous tracheostomy has been touted as the preferred route of tracheostomy.
      However, to date, no prospective randomized study comparing bedside percutaneous
      (BP) to bedside open (BO) tracheostomy has been performed. Surgical intensive
      care unit (sICU) patients were randomized to receive either a BP or a BO
      tracheostomy. Patients were monitored for complications. Procedure time was
      documented. A group of medical ICU patients had open tracheostomies in the
      operating room (OR) and served as contemporaneous controls. Over 11 months, there
      were 24 surgical ICU patients randomized to receive either BP tracheostomy or BO
      tracheostomy, 12 in each group. Forty-six medical ICU patients received standard
      open tracheostomy in the OR. The number of ventilator days before placing the
      tracheostomy was similar between the BP and BO groups, 9.8 and 12.4,
      respectively. The clinical indications for tracheostomy were similar between the
      two groups. The procedure time for the BP group was 14.5 minutes, whereas 25.2
      minutes for the BO group. There were no postprocedure complications in the BP and
      BO groups. There was a trend toward more complications in the BP group, including
      the loss of the airway, leading to death. The procedure time and complications
      were similar between the BO and OR groups. These data do not support that BP
      tracheostomy is the preferred route of tracheostomy when compared with BO
      tracheostomy. These data support that experienced surgical intensivists can
      perform BO tracheostomies with lower risk and cost, when compared with BP
      tracheostomy.

PMID- 9926750
TI  - Puerperal ovarian vein thrombosis with extension into the inferior vena cava.
AB  - The incidence of puerperal ovarian vein thrombosis is estimated to range between
      1 in 600 and 1 in 2000 deliveries. The cardinal signs of puerperal ovarian vein
      thrombosis include fever, leukocytosis, and right lower quadrant abdominal pain,
      most often in a recently delivered female patient. These patients are classically
      described as failing to improve with intravenous antibiotic therapy alone;
      resolution of symptoms and presumptive diagnosis is made on defervescence with
      the addition of intravenous heparin therapy. Objective diagnostic modalities
      include venography, ultrasound, laparoscopy, and MRI, although CT remains the
      gold standard for the identification of this under-diagnosed entity. We present a
      case report of a 20-year-old female treated at our facility for puerperal ovarian
      vein thrombosis. She was transferred to our vascular surgery service after
      developing the classic signs of puerperal ovarian vein thrombosis and undergoing
      CT demonstrating ovarian vein thrombosis with extension of free-floating thrombus
      into her inferior vena cava (IVC). This degree of thrombosis was particularly
      concerning when one considers the 3 to 33 per cent rate of pulmonary embolism
      reported in patients with puerperal ovarian vein thrombosis. Treatment modalities
      for such extensive degrees of thrombosis are described in the literature and
      range from hysterectomy and thrombectomy to ligation of the IVC. In our case, we
      prophylactically placed a suprarenal IVC Greenfield filter to protect against
      pulmonary embolism and proceeded with the standard regimen of anticoagulation and
      antibiotics. This treatment approach has been reported only twice previously in
      the literature, to our knowledge.

PMID- 9926751
TI  - Management of adrenal cysts.
AB  - Adrenal cysts have been traditionally managed by excision to rule out malignancy.
      We reviewed the 613 cases of adrenal cysts (including 6 new cases of our own) to
      evaluate whether this is still appropriate. Descriptive statistics and
      distribution of each pathologic type have been updated, based on 515 cases, and
      have changed from statistics compiled on 155 cases by G. A. Absehouse et al. Only
      seven per cent of all adrenal cysts are malignant or potentially malignant. There
      is only one reported case of a malignancy found in a nonfunctioning adrenal cyst
      that was initially thought to be benign. In this case, no CT or aspiration was
      performed. There have been 19 cases of adrenal cysts managed with aspiration. All
      were nonfunctioning and benign. One had a bloody aspirate. Reaccumulation
      occurred in 32 per cent of the cases (six cases); six per cent were symptomatic,
      four per cent were excised. Follow up was available in 15 cases from 4 months to
      3.5 years. Management of the patient with a suspected adrenal cyst should include
      a careful history and physical and biochemical screening to rule out a
      functioning lesion. A CT scan, and aspiration of the cyst with a cystogram should
      be performed to confirm a simple cyst of the adrenal. If the suspicion of
      malignancy is low, and the lesion is nonfunctional, the adrenal cyst may be
      managed by aspiration alone. If the cyst recurs and is asymptomatic, it may be
      observed. If a symptomatic cyst recurs, it may be reaspirated or excised.

PMID- 9926752
TI  - Management of deep vein thrombosis of the lower extremity in pregnancy: a
      challenging dilemma.
AB  - This study reviews our experience in the management of deep vein thrombosis (DVT)
      of the lower extremity during pregnancy and analyzes the outcome of various
      treatment alternatives, including conventional full-dose heparin therapy and
      Greenfield filter insertion. Twenty-four patients treated over an 8-year period
      were reviewed. Fifteen patients were treated with conventional full-dose
      intravenous heparin therapy for 5 to 10 days, followed by subcutaneous low-dose
      heparin until labor, and continued for 6 weeks postpartum (Group A); Eleven
      patients had Greenfield filters inserted, followed by the same low-dose
      subcutaneous heparin regimen (Group B). There were 18 femoral or iliofemoral, 5
      femoropopliteal, and 1 popliteal and below-knee DVT. The indications for
      Greenfield filter insertion included two patients in Group A (one with pulmonary
      embolism, despite adequate heparin therapy, and one with significant bleeding).
      Nine other patients had prophylactic indications: two for free-floating
      iliofemoral DVT, three with iliofemoral DVT (occurring just 1-2 weeks before
      labor), and four with femoropopliteal DVT. There were three immediate major
      complications (pulmonary embolism, bleeding, or death) in Group A; two with
      pulmonary embolism, one of which was fatal, and one with significant bleeding (3
      of 15 patients; 20%). No major complications occurred in Group B. On long-term
      follow-up (mean, 61 months), 4 of 12 patients (33%) in Group A had significant
      leg swelling, with partial resolution of DVT in 2 patients and venous occlusion
      in 2 patients by duplex ultrasound. This is in contrast to 3 of 11 patients (27%)
      in Group B with significant leg swelling. There was no fetal morbidity or
      mortality in either group. Conventional full-dose heparin therapy for DVT of the
      lower extremity in pregnancy can carry significant morbidity and mortality.
      Greenfield filters may be used safely in some of these patients.

PMID- 9926753
TI  - Central nervous system metabolic and physiologic effects of laparoscopy.
AB  - We set out to determine whether the increases in intracranial pressure (ICP)
      associated with CO2 insufflation had any metabolic effect on the central nervous
      system in a head injury when compared with gasless laparoscopy (GL). To test this
      hypothesis, we looked at both the ICP and jugular bulb venous saturation (JVS),
      with and without a coexisting cerebral mass lesion. Twenty-five kilogram male
      pigs had tracheostomy, epidural balloon, pulmonary arterial catheter, arterial
      line, and jugular bulb catheter placed. Intravenous Pentobarbital was used for
      anesthesia. Either CO2 laparoscopy (CL; n=7) or GL (n=7) were performed both with
      and without an epidural balloon inflated to a baseline ICP of 25. Data were
      analyzed using the Student's t test with a P value <0.05 being significant.
      Cerebral perfusion pressure and most hemodynamic values did not differ. Both
      central venous pressure and peak inspiratory pressure were significantly elevated
      whenever CO2 insufflation took place, reflecting an increased intrathoracic
      pressure. When comparing both study groups, the partial pressure of CO2 did not
      differ. CL increases ICP significantly above the gasless group in our head injury
      model. This is most likely secondary to increased intrathoracic pressure. The
      question still remains whether these changes are clinically significant. We could
      not demonstrate significant metabolic effects secondary to laparoscopy. In
      patients suffering head injury, GL rather than CL might be safer to avoid ICP
      elevation. Additional studies looking at central nervous system metabolic and
      objective histopathologic effects should be undertaken with larger numbers of
      study animals.

PMID- 9926754
TI  - A nomad of the winds.

PMID- 9926755
TI  - Pudendal canal: surgical anatomy and clinical implications.
AB  - The anatomy of the pudendal canal (PC) was studied in 26 cadavers: 10 stillborn
      and 16 adults (mean age, 48.2 years). Two approaches were used to expose the PC:
      gluteal and perineal. The PC was an obliquely lying tube with a mean length of
      0.8 cm in the stillborn and 1.6 cm in the adult cadavers. It started at a mean
      distance of 0.8 cm from the ischial spine in the stillborn and of 1.6 cm in the
      adult cadavers, and ended at a mean distance of 0.7 cm and 2.6 cm, respectively,
      from the lower border of the symphysis pubis. The PC wall was formed by the
      splitting of the obturator fascia and not by the lunate fascia. The PC contained
      the pudendal nerve and vessels embedded in loose areolar tissue. The three
      branches of the neurovascular bundle arose inside the canal in all but three
      cadavers. The wall of the PC consisted of collagen and elastic fibers, whereas
      that of the obturator fascia consisted of collagen only. The PC seems to be
      structurally adapted to serve certain functions. The criss-cross textile
      arrangement of collagen fibers in its wall allows the canal to change its shape
      in response to changes in pudendal vessels that occur during sexual activity. The
      elastic recoil may not only help to "pump" the blood up the pudendal vein, but
      also to prevent PC subluxation. The PC may, furthermore, act as a "pulley" for
      the neurovascular bundle. The pulley action may be disrupted by disordered pelvic
      floor muscles or defecation. Knowledge of the precise anatomy of the PC is
      necessary to carry out PC decompression in the treatment of PC syndrome.

PMID- 9926756
TI  - The "seat belt mark" sign: a call for increased vigilance among physicians
      treating victims of motor vehicle accidents.
AB  - The use of seat belts is shown to cause a specific pattern of internal injuries.
      Skin bruise corresponding to the site of the seat belt is known as the "seat belt
      mark" (SBM) sign and is associated with a high incidence of significant organ
      injuries. No study has yet defined the exact incidence of injuries requiring
      intervention at the presence of this sign. The objective of this study was to
      find the incidence of surgically correctable injuries in belted car occupants
      with a SBM sign and to define strategies of early detection and treatment of such
      injuries. The prospective study included consecutive patients involved in road
      traffic accidents who were admitted at an academic Level I trauma center. Of 650
      car occupants, 410 (63%) were restrained and 77 (12%) had a SBM across the
      abdomen, chest or neck. The injuries of these 77 patients were compared with the
      injuries of belted patients without an SBM sign. Of patients with SBMs, 9 per
      cent had neck bruises, 32 per cent had chest bruises, 40 per cent had abdominal
      bruises, and 19 per cent had bruises in multiple sites. No significant neck
      injuries were detected. Three patients were found to have myocardial contusion,
      and 10 patients had intra-abdominal injuries (predominantly bowel and mesenteric
      lacerations) requiring laparotomy. There was a near 4-fold increase in thoracic
      trauma (22.5% versus 6%; P=0.01) and a near 8-fold increase in intra-abdominal
      trauma (23% versus 3%; P < 0.0001) between the groups of patients with and
      without SBMs. The presence of the SBM sign should alert the physician to the high
      likelihood of specific internal injuries. Routine laparotomy or mandatory
      evaluation by specific diagnostic tests is not justified; rather, a high index of
      suspicion with a low threshold for appropriate diagnostic evaluation and/or
      surgical exploration should be maintained for the optimal management of such
      patients.

PMID- 9926757
TI  - Calot's triangle: loose interpretation or respectful accuracy?

PMID- 9926758
TI  - Re: Absorbable, delayed-release antibiotic beads reduce surgical wound infection.

PMID- 9926759
TI  - Re: Prevention of adhesions by Seprafilm, an absorbable adhesions barrier: an
      incisional hernia model in rats.

PMID- 9926760
TI  - Clinical pathways for general surgeons: esophagectomy.

PMID- 9926761
TI  - Periodontal repair in intrabony defects treated with a calcium sulfate implant
      and calcium sulfate barrier.
AB  - THIS RANDOMIZED, CONTROLLED, CLINICAL STUDY was designed to evaluate outcome
      following surgical implantation of an allogeneic, freeze-dried, demineralized
      bone matrix-calcium sulfate (DBM+CS) composite with a CS barrier in intrabony
      periodontal defects. Twenty-six patients contributing 26 deep intrabony defects
      completed the study. Thirteen patients received the DBM+CS implant. Thirteen
      patients received gingival flap surgery alone (GFS; control). Clinical outcome
      was assessed at 6 and 12 months postsurgery. At 12 months postsurgery, probing
      depth (PD) reduction (mean +/-SD) for the DBM+CS and GFS group was to 4.3+/-0.5
      and 3.0+/-1.3 mm; clinical attachment gain was to 2.9+/-0.8 and 1.7+/-1.5 mm; and
      probing bone level gain was to 2.9+/-1.4 and 1.2+/-1.2 mm, respectively. There
      were no apparent differences between evaluations at 6 and 12 months postsurgery.
      Clinical improvements were significantly different from presurgery for both
      groups at both observation intervals (P < 0.01). There were no significant
      differences between groups in PD reduction and clinical attachment gain. Probing
      bone level gain was significantly greater in the DBM+CS group compared to
      controls (P < 0.05). In summary, surgical implantation of DBM+CS with a CS
      barrier resulted in reduced PD and improved attachment levels comparable to that
      achieved by gingival flap surgery alone. However, gain in probing bone levels in
      deep intrabony periodontal pockets assessed by clinical parameters was greater
      than that observed by gingival flap surgery alone. These changes were noted at
      both 6 and 12 months after surgery. This regenerative technique needs further
      biologic evaluation before being generally accepted.

PMID- 9926762
TI  - An assessment of the osteoinductive potential of commercial demineralized freeze
      dried bone in the murine thigh muscle implantation model.
AB  - Early studies have demonstrated that implantation of laboratory preparations of
      demineralized freeze dried bone (DFDB) into the thigh muscle of mice induces
      ectopic osteoinduction. However, with the development of commercial preparations
      of DFDB for clinical use, concerns have been raised as to the osteoinductive
      properties of such preparations. The aim of this study was to investigate the
      osteoinductive potential of some commercial preparations of DFDB compared to a
      newly developed product which incorporates DFDB into a collagen sponge.
      Commercial preparations of DFDB or the DFDB/collagen sponge were inserted into
      the thigh muscles of 60 adult Swiss CD-1 mice. At the completion of each
      experimental period (7, 14, 30, 90 and 180 days), the animals were sacrificed,
      and the hindquarters of the mice were radiographed. The area where each graft had
      been placed was then excised, processed for light microscopy, and stained with
      hematoxylin and eosin or von Kossa's stain. Histological analysis of the
      DFDB/collagen sponges demonstrated significant remineralization which increased
      with time. Remineralization of the DFDB/collagen sponges was verified by
      radiographs which showed a significant increase in radiopacity over time. There
      was no radiographic evidence of mineralized tissue formation or remineralization
      in any of the commercial DFDB samples studied. At all time points studied,
      histological analyses failed to show evidence of bone formation for any of the
      preparations. The results suggest that commercially available DFDB is not
      osteoinductive in the murine model and question the use of such materials in
      clinical periodontics. The results found for the DFDB/collagen sponge indicate a
      different mechanism of activity from DFDB as evidenced by its rapid
      remineralization. The role this remineralization process has in osteoinduction is
      unknown and requires further study.

PMID- 9926763
TI  - Addition of human recombinant bone morphogenetic protein-2 to inactive commercial
      human demineralized freeze-dried bone allograft makes an effective composite bone
      inductive implant material.
AB  - COMMERCIAL PREPARATIONS OF HUMAN DEMINERALIZED freeze-dried bone allograft
      (DFDBA) vary in their ability to induce new bone formation. This study tested the
      hypothesis that inactive DFDBA can be used as an effective carrier of recombinant
      human bone morphogenetic protein-2 (rhBMP-2). Two batches of active DFDBA were
      used as controls. Two batches of DFDBA, previously shown to be inactive, were
      treated with vehicle or with 5 or 20 microg rhBMP-2 and implanted into the calf
      muscle of male Nu/Nu (nude) mice. Each mouse received one implant in each hind
      limb, both of which were of the same formulation, resulting in 8 groups of 4 mice
      per group: active DFDBA batch A, active DFDBA batch B, inactive DFDBA batch A,
      inactive DFDBA batch B, inactive DFDBA batch A plus 5 microg rhBMP-2, inactive
      DFDBA batch A plus 20 microg rhBMP-2, inactive DFDBA batch B plus 5 microg rhBMP
      2, and inactive DFDBA batch B plus 20 microg rhBMP-2. After 56 days, the implants
      were removed and histologically examined. A semiquantitative bone induction index
      was calculated based on the amount of new bone covering each histological
      section. Histomorphometry was also used to evaluate the area of new bone formed
      and the area of residual implant material. The results showed that active DFDBA
      induces new bone formation, whereas inactive DFDBA does not. Addition of rhBMP-2
      to inactive DFDBA results in new bone formation with a bone induction index
      comparable to that of active DFDBA. Histomorphometric analysis, however, revealed
      that the rhBMP-2-containing implants caused a dose-dependent increase in new bone
      area that exceeded that induced by active DFDBA. At the highest concentration of
      rhBMP-2, bone formation was exuberant. rhBMP-2 also caused the resorption of
      residual implant material to levels comparable to that seen in sites treated with
      active DFDBA, suggesting that this growth factor may regulate resorptive cells
      either directly or indirectly. This study shows that addition of rhBMP-2 to
      inactive DFDBA provides reproducible, consistent bone induction, and suggests
      that inactive commercial preparations may contain inadequate amounts of BMP to
      cause bone induction compared to active preparations.

PMID- 9926764
TI  - Evaluation of a bioactive glass alloplast in treating periodontal intrabony
      defects.
AB  - This study evaluated the use OF bioactive glass (BG) for repairing/regenerating
      periodontal intrabony defects. Fourteen systemically healthy patients
      participated. Each patient had 2 contralateral sites with > or = 6 mm clinical
      probing depth and radiographic evidence of an intrabony defect. One defect was
      treated with flap debridement plus BG (test) and the other with flap debridement
      alone (control). Baseline measurements included gingival index (GI), plaque index
      (PI), position of the free gingival margin (S/FGM), clinical attachment level
      (CAL), probing depth (PD), and mobility. At the time of surgery and at surgical
      reentry (9 to 13 months later), hard tissue measurements included: stent to
      defect base, bone crest to defect base, and defect width at the bone crest. One
      way repeated ANOVA was used to analyze the treatment effect. Friedman's test was
      used to detect any significant changes of GI, PI and mobility at different time
      periods (baseline, 3 months, 6 months, and reentry). For multivariate analysis,
      the random coefficients mixed effect model was applied to adjust the intra
      correlation effect. Both treatments resulted in decreased PD and gain of CAL.
      These changes were only significant (P < 0.05) for the BG treated sites (PD
      reduction = 1.24+/-0.43 mm, CAL gain = 0.87+/-0.38 mm) from baseline. Defect fill
      was significant for test (1.1+/-0.4 mm) and control (1.4+/-0.4 mm) alike (P < or
      = 0.01). Although BG treated sites had more PD reduction and CAL gain than
      debridement only controls, there were no statistically significant differences
      between groups for any parameter measured. Further studies are required to
      clarify the beneficial effects, if any, of BG alloplast in treating periodontal
      intrabony defects.

PMID- 9926765
TI  - Clinical and microbiological effects of adjunctive antibiotics in treatment of
      localized juvenile periodontitis. A controlled clinical trial.
AB  - The aim of this study was to assess the clinical and microbiologic effects of the
      combination of amoxicillin and metronidazole therapy as an adjunct to mechanical
      treatment in the management of localized juvenile periodontitis. Twenty-five
      localized juvenile periodontitis (LJP) patients from a Brazilian population were
      randomly allocated into an experimental group receiving mechanical treatment and
      antibiotics, and a control group receiving mechanical treatment and placebo.
      Clinical and radiographic assessments, as well as microbiologic sampling for
      Actinobacillus actinomycetemcomitans, were performed at baseline and one year
      after the end of the treatment. At the termination of the study A.
      actinomycetemcomitans could be isolated from the oral cavity of all patients in
      the control group who harbored the bacterium at baseline and in 4 out of 8
      patients in the experimental group. Both treatment modalities resulted in
      significant benefit on an individual basis. The experimental group, however,
      displayed better results than did the control group regarding gingival index
      (GI), probing depth (PD), clinical attachment level (CAL), and radiographic
      analysis of crestal alveolar bone mass, but not with respect to plaque index
      (PI). No serious adverse effects of the antibiotic treatment were observed in the
      present study.

PMID- 9926766
TI  - The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      and Bacteroides forsythus in humans 1 year after 4 randomized treatment
      modalities.
AB  - The relationship between probing attachment changes in treated periodontal
      pockets and the prevalence of selected periodontal pathogens was assessed in 10
      patients with adult periodontitis 1 year following randomized therapy. All
      patients had at least 1 tooth in each quadrant with an inflamed pocket of probing
      depth > or =5 mm and clinical attachment loss and harbored at least one of the
      following 3 major periodontal pathogens: Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, or Bacteroides forsythus. The number of target
      organisms per site was determined preoperatively; at 1 week; and at 1, 3, 6, and
      12 months postoperatively utilizing DNA probes. The following clinical parameters
      were measured and recorded preoperatively and at 1, 3, 6, and 12 months post
      treatment: gingival fluid flow, gingival index, plaque index, probing depth,
      probing attachment level, gingival recession, and bleeding on probing. One
      quadrant in each patient was randomly assigned to 1 of the following 4
      treatments: 1) scaling and root planing; 2) pocket reduction through osseous
      surgery and apically-positioned flap; 3) modified Widman flap; and 4) modified
      Widman flap and topical application of saturated citric acid at pH 1 for 3
      minutes. All 4 treatments were rendered in one appointment using local
      anesthesia. No postoperative antibiotics were used, but patients rinsed with
      0.12% chlorhexidine for the first 3 months postoperatively and received a
      prophylaxis every 3 months. This investigation revealed: 1) 30.0% of the sites
      were infected by at least 1 species at 3, 6, and 12 months postoperatively. 2)
      Failing sites were infected by a high number of both Pg and Bf These sites had a
      mean of 24.2+/-9.0 x 10(3) Pg and 93.1+/-42.0 X 10(3) Bf while stable sites had a
      mean of 6.8+/-0.5 x 10(3) Pg and 7.2+/-1.2 x 10(3) Bf (P = 0.06 and P = 0.05,
      respectively). 3) The infected sites lost significantly more mean clinical
      attachment at 12 months (1.5+/-0.5 mm compared to a loss of 0.2+/-0.3 mm for
      uninfected sites, P = 0.017). 4) The infected sites had a significantly greater
      BOP (67+/-14% versus 25+/-8% for uninfected sites at 12 months, P = 0.012). 5)
      The choice of treatment modality did not affect the prevalence of the target
      species at 1 year post-treatment. These results suggest that prevalence of
      microbial pathogens negatively affects the 1 year outcome of periodontal surgical
      and nonsurgical therapy.

PMID- 9926767
TI  - Diagnostic utility of specific microbiological markers for periodontal diseases.
AB  - Specific detection of marker organisms Porphyromonas gingivalis, Prevotella
      intermedia, and Actinobacillus actinomycetemcomitans with an immunoassay provided
      2 types of useful information directly into private clinical practice: 1)
      persistence of P. gingivalis in patients undergoing regular treatment allowed
      rapid identification of pockets requiring further treatment without waiting for
      measurable progression of lesions and 2) presence of A. actinomycetemcomitans in
      adults at any stage of diagnosis or treatment identified patients who may prove
      to have difficult-to-manage periodontitis. We made these findings in 253 patients
      (234 in specialist periodontal practices [F-ME 55; MHM 179] and 19 in general
      dental practice [EWM]). The search for useful diagnostic markers overlaps only
      partly with the search for periodontal pathogens. The P. gingivalis marker and
      the A. actinomycetemcomitans marker identify 2 different patterns of infection
      that appear to reflect 2 different underlying problems. Demonstration of pocket
      dependent infection with P. gingivalis in treated patients provides an outcome
      marker for sites not converting to marker-negative sites at detection levels of
      the immunoassay. This information facilitates selection of sites and patients
      requiring adjustment of treatment regimens. Detection of A. actinomycetemcomitans
      in adult patients is significantly associated with periodontitis characterized as
      refractory. Positive identification of A. actinomycetemcomitans with the
      immunoassay supports clinical decision-making by drawing attention to adult
      patients who require closer monitoring and intensive persistent treatment.
      Successful application of immunoassay detection of microbiological markers is
      based on continuous patient monitoring to support clinical decisions; it does not
      replace careful clinical judgment.

PMID- 9926768
TI  - Periodontitis-associated marker bacteria in an urban North American patient
      population: application of a commercial immunoassay.
AB  - We used an immunoassay to demonstrate marker organisms (Porphyromonas gingivalis,
      Prevotella intermedia, and Actinobacillus actinomycetemcomitans) in 3 private
      practice populations (F-ME periodontist, 55 patients; MHM periodontist, 179
      patients; and EWM general dentist, 19 patients). Occurrence of the marker
      organisms involves the whole oral environment, not just individual sites, as
      shown by close correlation between presence of the marker organisms in 2
      independent sites/samples within a single mouth. Presence of the marker P.
      gingivalis (and P. intermedia) relates closely to periodontal pocketing while
      presence of A. actinomycetemcomitans does not have this pocket-associated
      characteristic. There was no significant relationship between presence of the
      marker organisms and the number of teeth in a mouth, and in the periodontal
      practice patients there was no significant effect of gender on occurrence of the
      marker organisms. A. actinomycetemcomitans and the other 2 markers were found
      over the entire age range (12 to 75) of our patients. Regular periodontal
      treatment reduced occurrence of all marker organisms and increased the frequency
      of marker-negative patients and sites. Occurrence of the marker organisms above
      immunoassay threshold levels appears to represent how receptive a patient is to
      each individual organism. Most patients appear receptive to the presence of P.
      intermedia whether treated or not. Significantly fewer patients who underwent
      regular treatment show the presence of P. gingivalis or A. actinomycetemcomitans
      when compared to untreated patients. Diagnostic application of microbial markers
      requires ongoing clinical assessment of patients and careful clinical judgment.
      1391.

PMID- 9926769
TI  - The influence of endodontic infection on periodontal status in mandibular molars.
AB  - The purpose of the study was to investigate the influence of an endodontic
      infection on periodontal probing depth and presence of furcation involvement in
      periodontally-involved mandibular molars. All first and second mandibular molars
      in 100 patients were selected if at least one was root-filled or had a possible
      periapical radiolucency. The sample consisted of patients from a referral
      population at a periodontal clinic which represented an adult population with a
      mean age between 50 and 60 years. For mandibular molars with periapical
      destruction at both roots, mean periodontal probing depth was significantly
      greater compared to teeth without periapical destruction. Horizontal furcation
      depths > or =3 mm were significantly more frequent at mandibular molars with
      periapical destruction. It is suggested that a root canal infection in
      periodontitis-involved molars may potentiate periodontitis progression by
      spreading of endodontic pathogens through patent accessory canals and dentinal
      tubules. In conclusion, an endodontic infection in mandibular molars was found to
      be associated with additional attachment loss in the furcation area, and may thus
      be considered to be one of several risk factors influencing the prognosis of
      molars in periodontitis-prone patients.

PMID- 9926770
TI  - Sinus floor augmentation with simultaneous implant placement in the severely
      atrophic maxilla.
AB  - Dental implant placement associated with augmentation of the sinus floor in the
      severely atrophic maxilla can be performed in 1- or 2-surgical stages, depending
      on the height of the residual alveolar bone. A minimum of 4 to 5 mm of residual
      alveolar bone height is recommended for a 1-stage surgical procedure. The present
      study describes a 1-stage procedure in cases where the residual alveolar bone
      height in the posterior maxilla was 1 to 2 mm. A total of 55 hydroxyapatite
      coated dental implants were inserted in 20 grafted sinuses of 20 patients. No
      case presented any difficulty in achieving initial stabilization and parallelism.
      No perforation of the sinus membrane or clinical complications of the sinuses
      were evident. Prior to exposure, radiographic evaluation revealed bone
      consolidation and a close bone-implant relation. At second-stage surgery, there
      was no clinical evidence of crestal bone loss around the implants. All implants
      were clinically osseointegrated. All patients received fixed implant-supported
      prosthesis. The mean follow-up was 26.4 months (range 15 to 39 months). There was
      no implant loss after loading. The following surgical modifications are
      essential: a wide lateral window opening, the use of a bone mill to homogenize
      the bone graft, meticulous condensation, and clinical measurements to ensure
      implant parallelism.

PMID- 9926771
TI  - Factors affecting implant mobility at placement and integration of mobile
      implants at uncovering.
AB  - This study examined 1) factors that contributed to implant stability at placement
      and 2) the likelihood for an implant that was mobile at placement to
      osseointegrate. Eighty-one (3.1%) of 2,641 implants placed by the Dental Implant
      Clinical Research Group between 1991 and 1995 were found to be mobile at
      placement. Seventy-six (93.8%) of the 81 mobile implants were integrated at
      uncovering compared to 97.5% for the 2,560 immobile implants. Variables that
      influenced mobility at placement included patient age, implant design and
      material, anterior-posterior jaw location, bone density, and use of a bone tap.
      Hydroxyapatite (HA)-coated implants were slightly more likely to be mobile at
      placement (P = 0.324) than non-hydroxypatite (HA)-coated implants. Of the 54 HA
      coated implants that were mobile at placement, all (100%) integrated, while only
      17 (81.5%) of the 22 mobile non-HA-coated implants integrated (P = 0.003). Mean
      electronic mobility testing device values (PTVs) at uncovering for all implants
      mobile or immobile at placement that integrated were -2.9 and -3.6 respectively.
      PTVs for HA-coated implants that were mobile (-3.5 PTV) or immobile (-4.0 PTV) at
      placement differed by 0.5 PTV, whereas non-HA-coated implants exhibited a greater
      difference of 1.2 PTVs at uncovering. HA-coated implants, regardless of mobility
      at placement, integrated more frequently and exhibited greater stability than non
      HA-coated implants.

PMID- 9926773
TI  - Interleukin-1 and tumor necrosis factor antagonists inhibit the progression of
      inflammatory cell infiltration toward alveolar bone in experimental
      periodontitis.
AB  - Periodontal disease is a significant cause of tooth loss in humans and is one of
      the most prevalent diseases associated with bone loss. Following bacterial
      colonization, the gingiva becomes inflamed and, in some cases, progresses to
      destruction of alveolar bone. To investigate the temporal movement of
      inflammatory cells toward alveolar bone and the role of interleukin-1 (IL-1) and
      tumor necrosis factor (TNF) in this process, studies were carried out in a Macaca
      fascicularis primate model of experimental periodontitis. IL-1 and TNF activity
      was inhibited by local application of soluble receptors to IL-1 and TNF by
      injection into interdental papillae. The results indicate that following
      induction of experimental periodontitis, the front of inflammatory cells
      progresses toward alveolar bone and is associated with osteoclast formation.
      These processes are inhibited by blockers to IL-1 and TNF. These studies suggest
      that the conversion from gingivitis to periodontitis is directly associated with
      the movement of an inflammatory infiltrate toward alveolar bone, and that this
      activity is at least partially dependent upon IL-1 and/ or TNF.

PMID- 9926772
TI  - Neutrophil response and microbiological findings around teeth and dental
      implants.
AB  - The aim of this study was to compare the neutrophil response, measured as both
      functional and antigenic elastase, around teeth and titanium implants and to
      relate these findings to the microbiota. The 31 patients included in the study
      had been treated successfully for total or partial edentulism with titanium
      implants. Crevicular fluid and microbiological samples were taken from 3 sites:
      1) crevices around teeth and 2) implants in 16 partially edentulous patients and
      3) crevices around implants in 15 edentulous patients. All sites sampled showed
      similar degrees of inflammation assessed by gingival index and total protein
      concentration. The samples were analyzed for elastase activity and immunoreactive
      elastase. The elastase activity was significantly higher in crevices surrounding
      implants in partially edentulous patients compared with implants in edentulous
      patients. The antigenic elastase showed no difference among the 3 sites. Gram
      positive cocci were the main bacterial species in all 3 groups. Edentulous
      patients tended to have lower frequency of black pigmenting anaerobes. No
      correlation of analyzed bacteria and elastase activity was found between the 3
      sites. This study indicates that, despite a similar appearance of clinical
      parameters and absence of significant differences in the microbiota, the
      inflammation around implants in partially edentulous patients induces a stronger
      neutrophil response than does the inflammation around implants in edentulous
      patients.

PMID- 9926774
TI  - A comparison of 2 root coverage techniques: guided tissue regeneration with a
      bioabsorbable matrix style membrane versus a connective tissue graft combined
      with a coronally positioned pedicle graft without vertical incisions. results of
      a series of consecutive cases.
AB  - Root coverage procedures have become an important part of periodontal therapy.
      The purpose of this study was to compare 2 techniques, 1) guided tissue
      regeneration (GTR) with a bioabsorbable polylactic acid softened with citric acid
      ester membrane and 2) the connective tissue graft combined with a coronally
      positioned pedicle graft without vertical incisions. The GTR procedure produced a
      mean root coverage of 92.3% and the connective tissue graft combined with a
      coronally positioned pedicle graft, 95.0%. This difference was not statistically
      significant. Both procedures produced similar reductions in recession depth,
      recession width, and probing depth. The connective tissue graft combined with a
      coronally positioned pedicle graft resulted in a greater increase in the amount
      of keratinized tissue. Based on this study, both procedures can result in
      statistically similar amounts of mean root coverage, but the results are not
      identical. In most cases, the connective tissue with coronally positioned pedicle
      graft produced a more bulky result than guided tissue regeneration. Therefore,
      the procedures are not interchangeable.

PMID- 9926776
TI  - Tribute to 50 years and a look forward.

PMID- 9926775
TI  - Analysis of peripheral blood leukocytes in patients with cyclosporine A-induced
      gingival hyperplasia.
AB  - BACKGROUND: Gingival overgrowth is one of the major adverse effects of the
      immunosuppressive drug cyclosporine A (CsA). Although several studies have
      attempted to determine the immunological mechanisms of gingival hyperplasia (GO)
      due to CsA therapy, the pathogenesis remains unclear. In this study, the
      distribution of the peripheral blood leukocytes in a group of renal transplant
      patients undergoing CsA therapy was analyzed and possible correlations of
      periodontal and pharmacological variables to lymphocyte subpopulations, natural
      killer cells, and monocytes investigated. METHODS: Thirty-six patients were
      classified into 2 groups of 18 each according to the degree of gingival
      overgrowth. The periodontal evaluation included plaque index (PI), gingival index
      (GI), gingival overgrowth (GO), calculus index (CI), and probing depth (PD). The
      pharmacological variables of current doses of the therapeutic serum levels of CsA
      were investigated. The peripheral blood leukocytes were studied by 2-color flow
      cytometric analysis using anti-human CD2, CD3, CD4, CD8, CD11b, CD11c, CD16,
      CD19, HLA-DR, and CD3+HLA-DR+ monoclonal antibodies. RESULTS: Statistical
      evaluation revealed that none of the pharmacological variables varied between the
      2 groups. Responders (GO >30%) had significantly higher GI, PD, and GO scores
      compared to nonresponders (GO < or =30%). Of the immunological parameters
      studied, only CD2 was higher in the responder group. None of the clinical
      parameters correlated to the immunological values. CONCLUSIONS: The results of
      this study may be useful in explaining the underlying mechanisms of drug-induced
      gingival overgrowth. Several previously unsuspected cells and accessory
      activation mechanisms for T lymphocytes could play a role in the pathogenesis.

PMID- 9926777
TI  - Thomas G. Orr Memorial Lectureship. The general, general surgeon.

PMID- 9926778
TI  - A core breast biopsy diagnosis of invasive carcinoma allows for definitive
      surgical treatment planning.
AB  - BACKGROUND: We reviewed our image-guided core needle breast biopsy (IGCNBB)
      experience with patients diagnosed with invasive carcinoma (IC) to determine the
      accuracy of a core biopsy diagnosis of invasion and our ability to perform a
      single definitive cancer operation. METHODS: All IGCNBBs between July 1993 and
      July 1997 were reviewed to identify patients diagnosed with IC. Data included
      initial surgical treatment, surgical pathology, and subsequent surgical
      treatment. RESULTS: Of the 1,676 biopsies, invasive carcinoma was diagnosed in
      208 with follow-up in 204 cases. Invasive carcinoma diagnosis was confirmed in
      202 of 204 cases (99%). One hundred ninety-two patients had surgical treatment.
      Of these 192 patients, 173 (90%) could have achieved definitive surgical
      treatment with a single operation. CONCLUSIONS: An IGCNBB diagnosis of IC is
      accurate and allows for definitive breast cancer therapy. The potential impact on
      patient management is that a single operation can usually accomplish what
      traditionally has required at least two surgical procedures.

PMID- 9926779
TI  - Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy
      predict disease-free survival in patients with locally advanced breast cancer.
AB  - BACKGROUND: This study was performed to validate the prognostic significance of
      residual axillary lymph node metastases in patients with locally advanced breast
      cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other
      clinicopathologic factors that might be independent predictors of disease-free
      survival (DFS) in an attempt to identify patients in whom axillary dissection
      might be omitted. METHODS: One hundred sixty-five assessable patients with LABC
      were treated in a prospective trial of neoadjuvant chemotherapy utilizing four
      cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients
      were treated with segmental mastectomy and axillary dissection or modified
      radical mastectomy. Patients subsequently received additional chemotherapy
      followed by irradiation of the breast or chest wall and draining lymphatics. The
      median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant
      chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph
      nodes found at axillary dissection (P = 0.05) were the only independent
      predictors of DFS. Patients with a complete clinical response had a predictably
      excellent DFS and those with no change or progressive disease had a poor DFS. In
      patients with a partial response, the number of residual metastatic lymph nodes
      further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS:
      Clinical response and residual metastatic axillary lymph nodes following
      neoadjuvant chemotherapy are important predictors of DFS. Patients with a
      clinically positive axilla following neoadjuvant chemotherapy should undergo
      axillary dissection to ensure local control. However, the benefit of axillary
      dissection in patients with a clinically negative axilla may be minimal if the
      axilla will be irradiated, and histologic staging does not affect subsequent
      systemic treatment. A prospective randomized trial of axillary dissection versus
      axillary radiotherapy in patients with a clinically negative axilla following
      neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.

PMID- 9926780
TI  - Breast conservation surgery for breast cancer at a regional medical center.
AB  - BACKGROUND: This study examined trends in breast conservation surgery (BCS) at
      our hospital and factors associated with BCS. METHODS: We retrospectively
      reviewed breast cancer surgeries in patients eligible for BCS (size <4 cm, N0,
      N1) from 1990 through 1996 (n = 634). We calculated the yearly prevalence of BCS
      and used multiple logistic regression (MLR) to determine tumor, patient, and
      surgeon factors associated with BCS. RESULTS: BCS increased from 17% in 1990 to
      41% in 1996. Women with T1a and T1b tumors were 3.8 and 2.0 times, respectively,
      as likely to have BCS compared with those who had T2 tumors. Other factors
      associated with BCS included nonpalpable tumors, age <50, Medicare, Medicaid, or
      self-pay patients, and women whose surgeons graduated since 1961, with odds
      ratios of 1.8, 1.9, 2.4, and 2.3, respectively. CONCLUSION: Women with small,
      nonpalpable tumors, age <50, without private insurance, operated on by younger
      surgeons were more likely to receive BCS.

PMID- 9926781
TI  - How breast cancer treatment decisions are made by women in North Dakota.
AB  - BACKGROUND: Although equally effective, women in rural midwestern states choose
      modified radical mastectomy (MRM) over breast conservation surgery for early
      stage breast cancer. This study assessed treatment decisions by the women of
      North Dakota. METHODS: Surveys were sent to women treated for early stage breast
      cancer from 1990 through 1992. Separate surveys were sent out to surgeons in the
      state. The questions assessed physician and patient perceptions of treatment and
      the decision making process. RESULTS: A majority of surgeons believed that the
      long-term and disease-free survival was equal and that the preference for
      choosing MRM was due mostly to inconvenience of radiotherapy. The women reported
      that the surgeon was the most influential in the treatment decision and that
      concerns over radiation, duration of treatment, and travel restrictions all were
      factors in the decision. CONCLUSIONS: Education of surgeons and patients plus the
      early involvement of the radiation oncologist in discussing options is essential
      in the treatment of early stage breast cancer.

PMID- 9926782
TI  - Low rate of breast conservation surgery in large urban hospital serving the
      medically indigent.
AB  - BACKGROUND: Breast conservation surgery (BCS) with radiation therapy is an
      acceptable treatment for stage I and II breast carcinoma. The purpose of this
      study was to measure the use of BCS in a large, urban, university-affiliated
      hospital serving primarily medically indigent patients. METHODS: A chart review
      of patients receiving operative treatment for breast carcinoma during 1995 and
      1996 was done. Patients with stage I or II disease were selected. Data were
      analyzed for clinical stage, surgical treatment, age, and ethnic origin. RESULTS:
      Of patients eligible, only 16% received BCS. There were slight trends for younger
      women to receive BCS and for decreased use of BCS with stage II disease. No
      differences in surgical treatment were seen across ethnic groups. CONCLUSIONS: We
      suggest that poverty, poor education, and cultural differences may play a role in
      selection of surgical treatment for breast carcinoma. Further investigation is
      needed to facilitate best treatment.

PMID- 9926783
TI  - The evolving practice pattern of the breast surgeon with disappearance of open
      biopsy for nonpalpable lesions.
AB  - BACKGROUND: Recent advances in technology have prompted growth in the surgeon's
      armamentarium for breast biopsy. For nonpalpable, mammographically detected
      lesions, the options include stereotactic needle/wire localization and open
      biopsy (SNL/OBx), stereotactic needle core biopsy (SNCB), and directional, vacuum
      assisted biopsy (VAB; Mammotome). METHODS: A review of 372 patients with 424
      breast lesions biopsied by the same surgeon between January 1993 and August 1997
      was performed. RESULTS: SNCB and VAB procedures were less invasive and less
      morbid than SNL/OBx. Vacuum-assisted biopsy was superior to SNCB for sampling
      efficiency, with 74% of microcalcifications removed compared with 20% (P
      <0.0001). Additionally, underestimation of disease was seen with the SNCB
      technique, but not with VAB. Follow-up mammography found no false negative
      biopsies in any group. Over the 56 consecutive months, VAB progressively replaced
      SNL/OBx and SNCB as the procedure of choice. CONCLUSION: A breast surgeon can use
      VAB to replace open biopsy and core needle procedures for the initial biopsy of
      nonpalpable breast lesions.

PMID- 9926784
TI  - Sentinel lymph node biopsy, an alternative to elective axillary dissection for
      breast cancer.
AB  - BACKGROUND: Axillary metastases remain an important prognostic indicator in
      breast cancer. Axillary lymphadenectomy (ALND) carries significant morbidity and
      is unnecessary in most patients with early breast cancer; thus, sentinel lymph
      node (SLN) biopsy has been advocated for axillary staging. We studied the SLN
      identification rate and its accuracy in predicting axillary metastases. METHODS:
      One hundred nineteen women with breast carcinoma underwent SLN and ALND.
      Lymphoscintigraphy was performed using Technetium99 sulfur colloid supplemented
      by Isosulfan blue dye. Hematoxylin/eosin-stained lymph node sections were
      examined by light microscopy. RESULTS: The SLN identification rate was 81%. One
      SLN was negative (1%) in a patient with axillary disease. SLN histology correctly
      predicted the absence of axillary disease in 98.6%. Sensitivity, specificity, and
      positive and negative predictive values were 96%, 100%, 100%, and 99%,
      respectively. CONCLUSIONS: Sentinel lymph node biopsy accurately predicts total
      axillary status and is valuable in the surgical staging of breast cancer.

PMID- 9926785
TI  - Sentinel lymph node biopsy for staging breast cancer.
AB  - BACKGROUND: Determination of axillary nodal status is essential for the staging
      of breast cancer since nodal status is one of the most important predictors of
      survival. The objective of this study was to test the hypothesis that the
      histology of the first draining lymph node (LN) accurately predicts the histology
      of the rest of the axillary LNs. METHODS: Fifty-five patients with operable
      invasive breast carcinoma and clinically negative axillary lymph nodes were
      studied. Patients were injected with Technetium-99 (99Tc) sulfur colloid around
      the primary tumor. A hand-held gamma detector probe was used to identify the
      sentinel LN (SLN). After the SLN was identified and removed, a level I and II
      lymphadenectomy was performed. RESULTS: The SLN was identified in 53 (96.3%) of
      the 55 patients entered into the trial. The sensitivity was 88.2% and the
      specificity was 100%. The positive predictive value was 100% and the negative
      predictive value was 94.6%. The accuracy of the study was 96.2%. CONCLUSIONS: The
      SLN biopsy for breast cancer staging is highly accurate in our hands and has the
      potential to decrease the morbidity and cost of managing patients with breast
      cancer without compromise of staging.

PMID- 9926786
TI  - Management of casualties from the bombing at the centennial olympics.
AB  - BACKGROUND: The explosion of a bomb 75 to 100 yards away from attendees at a
      concert who were in the process of being evacuated from Centennial Olympic Park
      at approximately 1:25 AM on July 27, 1996, resulted in a multiple-casualty event
      involving primarily four hospitals in proximity to the blast. The purpose of this
      study was to review triage and care of the victims, emphasizing those with
      significant injuries. METHODS: Retrospective review of triage and care of injured
      patients. RESULTS: Ninety-six of the 111 victims of the blast were triaged in the
      first half hour to four hospitals within 3 miles of the bombing. Only four minor
      operations were performed in 61 patients evaluated at community hospitals. Ten of
      35 patients evaluated at the regional trauma center underwent emergency or urgent
      operations, and all who were seriously injured did well. CONCLUSIONS: Although
      overtriage to the regional trauma center occurred, outcome was excellent in all
      seriously injured victims treated there.

PMID- 9926787
TI  - Sentinel lymph node biopsy for melanoma.
AB  - BACKGROUND: The most powerful predictor of survival for patients with melanoma is
      the status of the regional lymph nodes. Sentinel lymph node biopsy may provide
      improved staging accuracy without the morbidity of elective lymph node dissection
      (ELND). METHODS: Sixty-eight patients with intermediate thickness melanoma
      underwent gamma probe guided sentinel node biopsy without ELND and were followed
      up over a mean of 22 months. RESULTS: A sentinel node was found in all patients.
      Six patients (9%) had positive sentinel nodes; all underwent complete
      lymphadenectomy. Two patients (3%) with negative sentinel nodes developed nodal
      recurrence; 1 of these patients was found to have microscopic disease on
      reexamination of the sentinel node. Two patients (3%) developed systemic disease.
      CONCLUSION: Gamma probe guided sentinel node biopsy can be performed with a high
      rate of technical success. It provides accurate pathological staging with a low
      incidence of nodal basin failure.

PMID- 9926788
TI  - Laparoscopic intraperitoneal onlay inguinal herniorrhaphy.
AB  - BACKGROUND: This study presents intermediate follow-up data on a randomized
      prospective series of patients undergoing either a modified laparoscopic
      intraperitoneal onlay mesh herniorrhaphy (IPOM) or conventional anterior inguinal
      herniorrhaphy (CH). METHODS: All patients from two university affiliated
      hospitals with primary or recurrent inguinal hernias were recruited for
      randomization to either the IPOM technique utilizing a meshed expanded
      polytetrafluorethylene (ePTFE) soft tissue patch or CH. Follow-up data were
      gathered from postoperative clinic visits and telephone and mail surveys.
      RESULTS: Previously reported early recurrence and complication rates at a mean
      follow-up of 8 months were 1 of 30 (3%) and 5 of 30 (17%) for IPOM, and 2 of 28
      (7%) and 5 of 28 (18%) for CH. Intermediate follow-up with 50 (23 IPOM and 27 CH)
      of the original 58 patients (86%) at a mean of 41 months reveals a recurrence
      rate of 10 of 23 (43%) for the IPOM group and 4 of 27 (15%) for the CH group (P =
      0.053). Five delayed complications occurred in 4 IPOM patients (port site hernia
      4, painful neuroma 1), while 2 delayed complications (unilateral testicular
      atrophy 2) occurred in 2 patients in the CH group. One IPOM versus 5 CH patients
      subsequently developed previously unrecognized contralateral hernias. There was 1
      death unrelated to previous herniorrhaphy in each group. CONCLUSIONS: IPOM
      recurrence rates (43%) at a mean follow-up of 41 months are excessively high when
      compared with CH (15%) or with preliminary results of IPOM at 8 months of follow
      up (3%). Despite reduced perioperative pain and disability and promising
      preliminary results in the IPOM group, these intermediate follow-up data strongly
      suggest that the IPOM technique should not be used for repair of inguinal
      hernias.

PMID- 9926789
TI  - Clinical, pathologic, and economic parameters of laparoscopic colon resection for
      cancer.
AB  - BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as
      treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91
      patients were entered into a prospective study of LCR for cancer. Clinical,
      pathologic, and economic parameters of LCR were compared in a cohort of patients
      matched for age, tumor stage, and type of colectomy who underwent open colon
      resection (OCR) during the same time period. RESULTS: With a median follow-up of
      26 months, there were no significant differences in survival rate for patients in
      the LCR, converted colon resection, and OCR groups. There were no port-site
      recurrences and the number of lymph nodes harvested was similar among the
      procedures. Hospital stay was significantly shorter if laparoscopic resection was
      successful. Total hospital costs were similar for LCR and OCR; however, the costs
      were significantly higher for converted colon resection. CONCLUSIONS: LCR is a
      sound oncologic procedure that can be performed with costs similar to OCR.

PMID- 9926790
TI  - Laparoscopic living donor nephrectomy and multiple renal arteries.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is a new technique. While the
      short-term recipient renal function is equivalent to that of the traditional open
      nephrectomy (ODN), long-term function and potential exclusion criteria, such as
      the presence of multiple renal arteries, are as yet unknown. METHODS:
      Retrospective review of 124 consecutive LDN performed from March 1996 to
      September 1997 with 117 ODN as historical controls. RESULTS: The 1-year actuarial
      graft and patient survival for LDN kidneys were 94% and 95%, respectively. These
      were not statistically different from that of the ODN controls. The presence of
      multiple renal arteries did not alter graft and patient survival or prevalence of
      immunologic events. The number of recipient ureteral complications in the LDN
      group was 11.2% compared with 3.4% in ODN (P < 0.01). Following correction for a
      learning curve with accompanying technical modifications, the prevalence of
      recipient ureteral complications has decreased to 7% in the last 94 patients (P =
      nonsignificant versus ODN). CONCLUSIONS: LDN represents a viable alternative to
      ODN for living renal transplants. Advantages for the donor are matched by
      equivalent functional results for the recipients.

PMID- 9926791
TI  - Results of laparoscopic antireflux surgery for dysphagia and gastroesophageal
      reflux disease.
AB  - BACKGROUND: Little attention has been paid to nonobstructive dysphagia (dysphagia
      in the absence of an esophageal stricture) in patients with gastroesophageal
      reflux disease (GERD). The objectives of this study were to assess (a) the
      incidence of nonobstructive dysphagia in patients with GERD; and (b) the effects
      of laparoscopic fundoplication on nonobstructive dysphagia. METHODS: Esophageal
      manometry and pH monitoring identified 666 patients with GERD. Two hundred and
      eight patients (31 %) without esophageal strictures complained of dysphagia in
      addition to heartburn and regurgitation. Forty-nine (24%) of these patients
      underwent laparoscopic fundoplication. Esophageal function tests were repeated
      postoperatively in 12 patients (25%). Main outcome measures were effects of
      laparoscopic fundoplication on symptoms and esophageal motor function. RESULTS:
      Dysphagia resolved postoperatively in 44 patients (90%), and improved in 2
      patients (4%). Postoperative esophageal manometry showed a significant increase
      in the length and pressure of the lower esophageal sphincter, without changes in
      its ability to relax in response to swallowing. CONCLUSIONS: About one third of
      GERD patients without strictures experienced dysphagia; and dysphagia resolved in
      about 90% of such patients following a laparoscopic fundoplication.

PMID- 9926792
TI  - Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's
      epithelium.
AB  - BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved
      in carcinogenesis. It was our aim to investigate whether reflux esophagitis may
      alter apoptosis in the esophageal mucosa and whether antireflux surgery may
      restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and
      postoperatively in esophageal biopsies of 39 patients with various grades of
      reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were
      also taken from lesions of the squamous epithelium adjacent to the Barrett's
      mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis
      was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa
      showed increased apoptosis. After surgery apoptosis decreased in squamous
      epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis
      in reflux esophagitis may be protective against increased proliferation. Low
      apoptosis following antireflux surgery indicates that surgery is effective to
      prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's
      may promote carcinogenesis. This may not change following surgery.

PMID- 9926793
TI  - Endovascular stent grafts for aneurysmal and occlusive vascular disease.
AB  - BACKGROUND: This report details our initial experience with two types of
      endovascular grafts- one for the treatment of infrarenal abdominal aortic
      aneurysms and the other for the treatment of iliac artery occlusive disease.
      METHODS: An abdominal aortic aneurysm was repaired in 34 patients using 3
      different types of Ancure endografts (Menlo Park, California). Control patients
      (n = 9) had a standard aneurysm repair. Patients with chronic lower extremity
      ischemia (n = 7) secondary to iliac artery occlusive disease were treated with a
      Hemobahn endograft (W. L. Gore & Associates, Flagstaff, Arizona). RESULTS: Ancure
      graft deployment was achieved in 33 of 34 (97.1%) patients. Perioperative
      mortality for the Ancure and control group patients was 2.9% and 0%,
      respectively. Periprosthetic leaks were identified within 48 hours of deployment
      in 6 (18.2%) Ancure graft patients. All but 2 of the leaks resolved on serial
      follow-up. Additional endovascular procedures were required in 11 (32.4%) Ancure
      graft patients at the initial procedure or during follow-up to correct graft or
      arterial stenoses. Patients treated with an endovascular graft had significantly
      less blood loss and shorter hospital stays than control group patients. For
      Hemobahn patients, the technical success for graft deployment was 100%. There
      were no perioperative deaths. The ankle/brachial index increased from a mean of
      0.52 preoperatively to 0.86 postoperatively (P = 0.004). One patient required a
      Wallstent in follow-up to correct a graft wrinkle. Angiography at 6 months
      demonstrated mild intimal hyperplasia in the stent graft in 5 of 6 patients.
      CONCLUSIONS: These early results support the potential for endovascular grafts in
      the treatment of aneurysmal and occlusive vascular disease. Further modifications
      in the devices and deployment techniques are necessary to reduce the incidence of
      periprosthetic leaks, graft limb stenoses, and intimal hyperplasia.

PMID- 9926794
TI  - Appropriate timing of elective coronary artery bypass graft surgery following
      acute myocardial infarction.
AB  - BACKGROUND: The appropriate timing of elective coronary artery bypass surgery
      (CABG) following acute myocardial infarction (AMI) remains uncertain. It is
      hypothesized that a waiting period allows the myocardium to recover prior to
      revascularization, thus decreasing morbidity and mortality. This study was
      designed to determine if a waiting strategy is justified following AMI in
      patients requiring elective CABG. METHODS: Between 1994 and 1996, 214 patients
      underwent isolated, nonrepeat, elective CABG. Three groups were evaluated: group
      I, control, 155 patients with no AMI; group 11, 39 patients with nontransmural
      AMI; and Group III, 20 patients with transmural AMI. Demographics,
      intraoperative, and postoperative variables were collected and compared among all
      groups. RESULTS: Groups were well-matched demographically: group I, patients
      waited an average of 2.3 days in hospital prior to operation; group II, an
      average of 4.2 days; and group III, an average of 5.2 days. Except for the use of
      inotropes, group I 34%, group 11 39%, and group III 70% (P = 0.007), and the
      intra-aortic balloon pump, group I 0%, group 11 8%, and group III 25% (P =
      0.001). There were no differences in complications. Importantly, there was no
      difference in mortality or postoperative length of stay. The mortality in group I
      was 2.6%, in group 11 2.6%, and in group III 0%. The length of stay in groups I
      and II was 8.5 days, and in group III, 8.1 days. CONCLUSION: A waiting period of
      3 to 5 days after a nontransmural AMI and 5 to 7 days after a transmural AMI can
      produce similar postoperative results to non-AMI patients undergoing CABG. Thus,
      a waiting strategy to allow the myocardium to recover is justified.

PMID- 9926795
TI  - Endoscopic saphenous vein harvest in infrainguinal bypass surgery.
AB  - BACKGROUND: Autologous greater saphenous vein is considered to be the optimal
      material for peripheral arterial reconstruction and coronary artery
      revascularization. We describe a new endoscopic technique of saphenous vein
      harvest in infrainguinal arterial bypass surgery. METHODS: A retrospective
      analysis of 64 infrainguinal bypass procedures was performed comparing the
      standard open technique of saphenous vein harvesting with a new less invasive
      endoscopic technique. RESULTS: There were no differences in age, gender,
      indications for surgery, or proximal or distal anastomosis between the two
      groups. There were also no significant differences in early wound complications,
      early patency, and transfusion requirements. In the endoscopic group, length of
      operation was longer (189 versus 158 minutes; P <0.005), length of stay was
      shorter (5.2 versus 8.1 days; P <0.05), and postoperative day of discharge was
      also less (3.3 versus 5.5 days; P <0.01). CONCLUSIONS: Our findings indicate that
      endoscopic saphenectomy is technically feasible, leads to earlier discharge from
      the hospital, and leads to increased operative time. Most importantly, the
      procedure can be performed safely without subjecting the patient to increased
      risk.

PMID- 9926796
TI  - Evaluating institutional variability of duplex scanning in the detection of
      carotid artery stenosis.
AB  - PURPOSE: Duplex scanning is widely used to measure carotid artery stenosis, but
      the issue of variability between institutions must be raised. To examine for this
      potential variability, we evaluated two ATL Ultramark 9 duplex machines at two
      hospitals within our institution. METHODS: Stenosis was calculated
      angiographically as in the North American Symptomatic Carotid Endarterectomy
      Trial (NASCET). Internal carotid artery (ICA) to common carotid artery (CCA) peak
      systolic velocity (PSV) ratios were determined using the two ATL machines.
      Receiver operating characteristic (ROC) curves were generated for each hospital.
      RESULTS: ROC curves varied significantly. The area under the curve from hospital
      1 was 0.95 (SE = 0.021); the area under the curve from hospital 2 was 0.87 (SE =
      0.034). The curves were essentially statistically different (P = 0.0516).
      COMMENTS: We showed a difference in predicting diameter stenosis utilizing ICA
      PSV/CCA PSV ratios at two hospitals within our institution. Variability is likely
      due to technologists, since equipment and physician interpreters were the same.
      Criteria must be developed for each different machine in each laboratory. Quality
      assurance is critical to minimize variability.

PMID- 9926797
TI  - Vena caval occlusion after bird's nest filter placement.
AB  - BACKGROUND: Inferior vena caval thrombosis as a result of intracaval barrier
      devices occurs in 6.5% of patients with Greenfield filters. The incidence is less
      well defined in patients in whom bird's nest filters have been placed. We
      reviewed our experience with bird's nest filters to determine the incidence of
      filter-induced caval thrombosis. METHODS: The records of 140 patients with bird's
      nest filters were reviewed, living patients were interviewed, and the inferior
      vena cava examined in 37 patients by duplex scanning. RESULTS: Ninety-three
      patients were available for evaluation. Five of these patients were found to have
      caval thrombosis by duplex scanning and 2 had clinical symptoms and signs
      compatible with caval thrombosis. The majority of these patients were on
      anticoagulants at the time of filter thrombosis. CONCLUSION: The incidence of
      filter-induced vena caval thrombosis in patients with bird's nest filters (7%) is
      comparable with that of Greenfield filters. Because of the catastrophic
      manifestations of this complication and the increasing application of vena caval
      filters, the role of these filters in the treatment of thrombotic disease needs
      further critical evaluation.

PMID- 9926799
TI  - Reduced transfusion requirements during major hepatic resection with use of
      intraoperative isovolemic hemodilution.
AB  - BACKGROUND: Allogeneic blood transfusion during liver resection for malignancies
      has been associated with an increased incidence of tumor recurrence and decreased
      survival in some series. Isovolemic hemodilution (IH) has been utilized in
      cardiac, orthopedic, and major general surgery procedures to reduce the use of
      banked blood products. We therefore sought to determine the safety and efficacy
      of IH during major hepatic resection in an adult population. METHODS: Thirteen
      consecutive patients undergoing major hepatic resection with IH were compared
      with 13 age- and disease-matched controls. The diseases included metastatic
      colorectal adenocarcinoma (8 versus 9), hepatoma (2 in each group) and other (3
      versus 2); and the procedures included total (right or left) hepatic lobectomy (8
      versus 11), partial lobectomy (3 versus 1) and trisegmentectomy (2 versus 1).
      RESULTS: There was no significant difference in operating time, estimated blood
      loss, fresh frozen plasma, platelets, amount of crystalloid or colloid infused
      between the two groups. There was no perioperative morbidity related to IH. The
      use of IH resulted in a 60% reduction in mean packed red blood cells transfusion
      during major hepatic resection. Only 38% of patients undergoing IH required
      packed red cells transfusion, whereas 77% of historical control patients required
      allogenic transfusion. CONCLUSION: The use of IH reduces the need for homologous
      transfusion during major hepatic resection. IH is a safe technique during hepatic
      resection and is not associated with perioperative morbidity.

PMID- 9926798
TI  - Vein patching reduces neointimal thickening associated with prosthetic graft
      implantation.
AB  - PURPOSE: Modified anastomotic techniques utilizing autogenous vein-cuffs or
      patches have been devised with the hope of improving prosthetic graft patency.
      The mechanisms of the presumed improvement in patched anastomoses have never been
      elucidated and remain speculative. We characterized the healing response of the
      Taylor vein patch in prosthetic arteriovenous fistulae in a canine model of
      intimal hyperplasia. METHODS: Six adult dogs underwent placement of bilateral (6
      patched, 6 control) 4-mm diameter expanded polytetrafluoroethylene loop femoral
      artery-vein fistulae. Serial duplex ultrasound examinations confirmed graft
      patency until explant at 6 weeks. Differential light microscopy with computerized
      image analysis was performed on serial 5-microm sections. Intimal thickness
      through the venous anastomosis and outflow veins of Taylor patch and control
      (nonpatched) grafts were compared. Cell type-specific immunocytochemical antibody
      stains for smooth muscle cells (alpha SMC actin) and endothelial cells (von
      Willebrand factor) were performed. RESULTS: Eleven of 12 grafts remained patent
      for 6 weeks, 1 control graft thrombosed. Mean duplex-derived peak systolic
      velocities of patched (96 cm/sec) and control (108 cm/sec) grafts were similar.
      Microscopy revealed more intimal pannus anastomotic suture line ingrowth in
      controls (mean thickness = 178 microm) than Taylor patched grafts (mean 147
      microm, p = 0.0002). Significantly less intimal thickening was present in the
      outflow vein of patched (mean thickness = 90 microm) versus control grafts (mean
      195 microm, P <0.0001). The intima maintained a single cell layer of vWF +
      endothelial cells, while the majority of the cells comprising the lesion
      expressed alpha SMC actin. CONCLUSION: Perianastomotic pannus is primarily
      composed of intimal smooth muscle cells. Neointimal thickening is significantly
      reduced in prosthetic arteriovenous fistulae created with the Taylor vein patch
      in a canine model. Reduction in perianastomotic intimal thickening may explain
      the reported clinical improvement in prosthetic bypass graft patency when
      modified with vein patch techniques.

PMID- 9926800
TI  - Resuscitation of the injured patient with polymerized stroma-free hemoglobin does
      not produce systemic or pulmonary hypertension.
AB  - BACKGROUND: Hemoglobin-based blood substitutes appear poised to deliver the
      promise of a universally compatible, disease-free alternative to banked blood.
      However, vasoconstriction following administration of tetrameric hemoglobins has
      been problematic, likely because of nitric oxide binding. Polymerized hemoglobin
      is effectively excluded from the abluminal space because of its size, and is thus
      less likely to perturb vasorelaxation. We therefore hypothesized that hemodynamic
      responses would be no different in injured patients receiving polymerized
      hemoglobin versus banked blood. METHODS: Injured patients requiring urgent
      transfusion were randomized to receive either polymerized hemoglobin or banked
      blood. Systemic arterial pressure, pulmonary arterial pressure, cardiac index,
      pulmonary capillary wedge pressure, systemic vascular resistance, and pulmonary
      vascular resistance were measured serially. RESULTS: There was no difference in
      any of the measured hemodynamic parameters between patients resuscitated with
      polymerized hemoglobin versus blood. CONCLUSIONS: Polymerized hemoglobin given in
      large doses to injured patients lacks the vasoconstrictive effects reported in
      the use of other hemoglobin-based blood substitutes. This supports the continued
      investigation of polymerized hemoglobin in injured patients requiring urgent
      transfusion.

PMID- 9926801
TI  - Routine chest radiographs following central venous recatheterization over a wire
      are not justified.
AB  - BACKGROUND: Subclavian vein central venous catheterization and the subsequent
      exchange of subclavian catheters over a guidewire are frequently performed
      procedures. We hypothesized that the policy of obtaining a routine postprocedure
      chest radiograph to confirm appropriate catheter placement and to rule out
      complications after exchanging central venous catheters over a wire was no longer
      justifiable. METHODS: A retrospective study of 295 patients with Swan-Ganz
      catheters (SGC) was performed between July 1, 1994 and June 30, 1996. One hundred
      fourteen of these SGCs were exchanged over a guidewire for a central venous
      catheter (CVC). Postexchange chest radiograph and associated radiologist's
      report, as well as age, gender, and duration of catheter placement were all
      recorded. Since July 1996, this study has been extended prospectively. RESULTS:
      Of the 380 documented over-a-wire exchanges, none has resulted in a complication,
      including catheter malposition. CONCLUSION: We conclude from these data that a
      routine chest radiograph following the replacement of a CVC over a guidewire is
      not necessary when good clinical judgment and discrimination are used in a
      monitored setting.

PMID- 9926802
TI  - Surgical experience with implantable insulin pumps. Department of Veterans
      Affairs Implantable Insulin Pump Study Group.
AB  - BACKGROUND: A recent Veterans Affairs cooperative trial demonstrated that
      intensive insulin therapy via an implantable pump with intraperitoneal insulin
      delivery reduced glycemic variability and improved quality of life compared with
      multiple daily insulin injections. Our aim was to determine perioperative
      morbidity and assess long-term function of the implantable insulin pump. METHODS:
      Fifty-one adult patients with type 2 diabetes had infusion pumps placed over a 2
      year period at seven VA Medical Centers as part of a randomized prospective
      study. RESULTS: All pumps were placed successfully. There were two (4%)
      perioperative complications. There were no wound complications. Duration of pump
      use ranged from 12 to 25 months (mean 20). Catheter obstruction (57%) and pump
      malfunction (25%) were the most common reasons for pump explantation. Catheter
      occlusions increased after 12 months. Catheter occlusion was treated by
      percutaneous rinse procedure in 75% and revisional procedures in 31% of patients.
      CONCLUSIONS: Implantable insulin pumps can be placed with minimal surgical
      morbidity. Attention to surgical detail and infusion protocol permits
      satisfactory long-term function. Pump/catheter complications increase with time
      but are usually resolvable by either operative or percutaneous manipulations.

PMID- 9926803
TI  - Cholecystectomy in patients aged 80 and older.
AB  - BACKGROUND: We assessed whether the increase in performance of laparoscopic
      cholecystectomy has affected patients aged 80 and older and if outcomes of a
      laparoscopic approach in this population would show improvement over those for
      open surgery. METHODS: We analyzed an 11-state discharge database obtained from
      the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project.
      Release 1 contains a 20% sample of United States hospitals for the period 1988 to
      1992. Diagnosis-related group (DRG) codes 197 and 198 were searched, and
      demographics, type of surgery, and outcome measures were analyzed. RESULTS: In 5
      years, 350,451 patients underwent cholecystectomy with the DRG codes listed. Of
      those, 18,500 patients were aged 80 to 105. The total number of cholecystectomies
      increased each year. Performance of laparoscopic cholecystectomy rose rapidly and
      that of open cholecystectomy decreased. Overall mortality with laparoscopic
      cholecystectomy was 1.8%, was lower than that of open cholecystectomy, was lower
      in women, and decreased with time. CONCLUSIONS: Patients aged 80 and older have
      participated in the increased performance of cholecystectomy and the switch to
      laparoscopic cholecystectomy. This has a low mortality, low length of stay, and
      higher proportion of patients being discharged to home compared with patients
      having open cholecystectomy.

PMID- 9926804
TI  - Routine intraoperative laparoscopic cholangiography.
AB  - BACKGROUND: Whether intraoperative laparoscopic cholangiography should be routine
      is debatable. METHODS: We reviewed the cholangiography experience in 669
      consecutive laparoscopic cholecystectomies. RESULTS: Mean age of the patients was
      39 years, 78% were female, and 29% had acute cholecystitis. Cholecystectomy was
      completed laparoscopically in 606 (91%). Laparoscopic cholangiography was
      completed in 562 (93%) and 348 (62%) were routine (no preoperative indication).
      The mean operating time in 1996 was 61 minutes. Out of the 348 routine
      cholangiograms, 17 demonstrated evidence of unsuspected choledocholithiasis. Five
      patients had choledocholithiasis documented by laparoscopic common bile duct
      exploration and/or endoscopic retrograde cholangiopancreatography. Two patients
      had normal postoperative cholangiopancreatography. One of 10 patients managed
      expectantly was readmitted postoperatively with obstructive jaundice. In 4
      patients, routine cholangiography revealed unexpected anatomy, and in 2, this
      prevented misidentification and transection of the common bile duct. CONCLUSION:
      Laparoscopic cholangiography is safe, quick, detects unsuspected
      choledocholithiasis, and can prevent common bile duct transection. It should be
      routine.

PMID- 9926805
TI  - Cost-effective management of gynecomastia.
AB  - BACKGROUND: Routine endocrine screening of idiopathic gynecomastia has been
      advocated, but may not be cost effective. We carried out a cost-benefit analysis
      of this approach. METHODS: A retrospective study (1992 to 1997) of 87 adult males
      with symptomatic gynecomastia was performed. RESULTS: Thirty-four (39%) patients
      had extrinsic causes; 53 (61%) were considered idiopathic. Forty-five idiopathic
      cases underwent endocrine testing: beta human chorionic gonadotropin alone, 16;
      and beta human chorionic gonadotropin, LH, estradiol, testosterone+/-testicular
      ultrasound, 29. One (2%) occult Leydig cell testicular tumor was detected. Forty
      four patients had normal studies and remain well after local excision.
      CONCLUSION: Routine endocrine evaluation of idiopathic gynecomastia is rarely
      productive; such testing is best done selectively.

PMID- 9926807
TI  - Decreased mortality from necrotizing pancreatitis.
AB  - BACKGROUND: Necrotizing pancreatitis has been associated with mortality rates of
      25% to 80%. We reviewed our experience to determine whether aggressive
      debridement and comprehensive critical care improves survival. METHODS: The
      records of 989 patients with the diagnosis of pancreatitis admitted between
      January 1990 and September 1997 were retrospectively reviewed. Twenty-six
      patients required surgery for necrotizing pancreatitis and are the subjects of
      this review. RESULTS: Five of twenty-six patients (19%) died. For all patients,
      mean Ranson's score was 4.3 of 11, mean admission APACHE II score was 17.2, and
      mean Multiple Organ Dysfunction (MOD) score was 9.1. Poor outcome was associated
      with infected pancreatic necrosis (P = 0.03), elevated APACHE II score on
      admission (P = 0.04), and progression of MOD during the week after admission (P =
      0.02). CONCLUSIONS: This review demonstrates improved survival in seriously ill
      patients with necrotizing pancreatitis as a result of comprehensive surgical and
      critical care.

PMID- 9926806
TI  - Differential effect of radiation on endothelial cell function in rectal cancer
      and normal rectum.
AB  - BACKGROUND: Chronic radiation injury of the intestine is associated with
      significant underexpression of a potent physiological anticoagulant, endothelial
      cell thrombomodulin (TM). This study compared early and late radiation-induced
      changes in endothelial TM, urokinase plasminogen activator (uPA), and
      transforming growth factor beta (TGF-beta) in normal rectum and tumors. METHODS:
      Rectal resection specimens from 27 patients were analyzed: Nine patients
      underwent primary resection of rectal cancer, 11 tumors were resected after neo
      adjuvant radiotherapy, and 7 because of local recurrence after prior resection
      and adjuvant radiotherapy. TM, uPA, and extracellular matrix-associated TGF-beta,
      immunoreactivity were assessed using computerized image analysis. RESULTS:
      Multivariate analysis revealed that tumors had more TM-positive vessels (P =
      0.003), more uPA-positive cells (P <0.001), and higher TGF-beta immunoreactivity
      levels (P <0.001) than normal rectum. Preoperative irradiation was associated
      with decreased proportions of TM-positive vessels in tumors (P = 0.003) and
      normal rectum (P <0.001). Irradiated tumors had fewer uPA-positive cells (P =
      0.003) and less TGF-beta immunoreactivity (P = 0.001) than unirradiated tumors.
      The proportion of TM-positive vessels in irradiated rectum from patients with
      recurrence was decreased (P = 0.03), whereas the recurrent (ie, unirradiated)
      tumors did not differ from primary tumors in terms of TM, TGF-beta, or uPA
      immunoreactivity. CONCLUSIONS: The results support a role for endothelial
      dysfunction in the pathogenesis of radiation proctitis. Maintaining endothelial
      cell anticoagulant function may be a potential method to optimize the therapeutic
      ratio of adjuvant radiotherapy of rectal cancer.

PMID- 9926808
TI  - Experience with minimally invasive surgery in infants.
AB  - BACKGROUND: This study evaluates the feasibility, safety, and efficacy of
      performing advanced endoscopic procedures in infants under 5 kg. METHODS: Over a
      51-month period 183 infants weighing 1.3 to 5.0 kg underwent 195 procedures using
      minimally invasive techniques. The majority of the procedures were performed
      using 3.5-mm instruments and 2.7-mm scopes. Procedures include Nissen
      fundoplication, pyloromyotomy, colon pull-through, patent ductus arteriosus
      closure, Ladd's procedure, colon resection, congenital diaphragmatic hernia
      repair, ovarian cyst excision, and exploration. RESULTS: All but two procedures
      were completed successfully endoscopically. There were two intraoperative
      complications and no mortality. Days to discharge for patients admitted for their
      specific procedure were Nissen 2.1, patent ductus arteriosus 2, pyloromyotomy 1,
      and pull-through 3.4. CONCLUSIONS: This study demonstrates that advanced
      endosurgical techniques in infants is safe, effective, and associated with the
      same benefit as that seen in older patients.

PMID- 9926810
TI  - Choosing the best abdominal closure by meta-analysis.
AB  - BACKGROUND: Local custom, rather than evidence-based medicine, dictates how a
      surgeon closes abdominal wounds. Closures might be more secure if grounded on
      statistical data. MATERIALS AND METHODS: A meta-analysis of 12,249 patients with
      abdominal wound closures was made. Infections, hernias, and dehiscences were
      compared examining continuous versus interrupted closures, continuous (absorbable
      versus nonabsorbable), interrupted (absorbable versus nonabsorbable), and mass
      versus layered. RESULTS: Continuous absorbable closures showed more hernias (P =
      0.0007). Dehiscences were significantly more with continuous nonabsorbable suture
      (P = 0.01). Interrupted nonabsorbable closures showed a higher incidence of
      hernias and dehiscences (P = 0.0002, P = 0.04). Mass closures produced
      significantly less hernias and dehiscences when compared with layered closures (P
      = 0.02, P = 0.0002). CONCLUSIONS: Continuous closures with nonabsorbable suture
      should be used to close most abdominal wounds. However, if infection or
      distention is anticipated, interrupted absorbable sutures are preferred. Mass
      closures are superior to layered closures.

PMID- 9926809
TI  - Comparison of laparoscopic versus open repair of paraesophageal hernia.
AB  - BACKGROUND: Recent reports suggest that laparoscopic paraesophageal hernia repair
      (LPHR) is feasible, but no direct comparisons with the standard open
      paraesophageal hernia repair (OPHR) have been reported. The purpose of this study
      was to compare the short-term outcome of LPHR versus OPHR at a single
      institution. METHODS: The operative and postoperative courses of 95 consecutive
      patients undergoing open or laparoscopic repair of a paraesophageal hernia (PEH)
      were retrospectively reviewed, and outcomes of LPHR versus OPHR were compared.
      RESULTS: PEH was associated with advanced age and significant comorbidity.
      Although the operative time was increased for LPHR, there was a significant
      reduction in blood loss, intensive care unit stay, ileus, hospital stay, and
      overall morbidity associated with LPHR compared with OPHR. CONCLUSIONS: PEH is
      associated with significant comorbidity that increases the operative risk. Short
      term outcomes for LPHR are superior to OPHR, suggesting that the laparoscopic
      approach is the preferred approach to paraesophageal hernia repair.

PMID- 9926811
TI  - Preoperative cardiac evaluation is unnecessary in most patients undergoing
      vascular operations.
AB  - BACKGROUND: This study evaluated the impact of Goldman's index (GI), radionuclide
      ventriculography (RVG), and dipyridamole-thallium scintigraphy (DTS) on
      predicting cardiac outcome after vascular operations. METHODS: A total of 463
      consecutive patients undergoing vascular operations were divided into those who
      had no DTS, those who had reversible ischemia by DTS, and those who had no
      reversible ischemia by DTS. GI, ejection fraction, wall motion abnormalities,
      rate of coronary angiography, and revascularization were determined for each
      group. RESULTS: Coronary revascularization was ultimately performed in 8% of
      patients with no DTS, 7% of patients with no ischemia by DTS, and 9% of patients
      with ischemia by DTS. The GI of 6.1 in patients who died postoperatively was
      significantly higher than the GI of 3.6 in patients who survived (P = 0.02). RVG
      did not predict mortality, morbidity, or need for coronary revascularization.
      CONCLUSION: Clinical assessment remains a good predictor for cardiac outcome in
      patients undergoing vascular operations. More extensive cardiac testing should be
      reserved for patients with higher GI and active cardiac problems.

PMID- 9926812
TI  - Assuring competency in clinical breast evaluation skills.

PMID- 9926813
TI  - Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired
      on spatial scene learning and object reversals.
AB  - Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or
      parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic
      acid) and unoperated controls were tested on object discrimination and reversal,
      place discrimination and reversal, and spatial scene learning to determine the
      contribution of these temporal lobe structures to these forms of learning and
      memory. Rhinal cortex lesions produced a severe deficit in object reversal
      learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal
      cortex removals and those with hippocampal lesions were equally impaired on
      spatial scene learning. None of the lesions impaired place discrimination or
      reversal. These results argue against the idea that the mnemonic contributions of
      the rhinal cortex and hippocampus are limited to object and spatial domains,
      respectively.

PMID- 9926814
TI  - Sex-sensitive tasks in men and women: a search for performance fluctuations
      across the menstrual cycle.
AB  - This study validated 6 cognitive and motor-skill tasks as sex-sensitive and used
      them to investigate whether women's performance changed across the menstrual
      cycle. Three putative female-advantage tasks and 3 putative male-advantage tasks
      were administered twice, at 6-week intervals, to young college women and men.
      Counterbalanced for order, women received the tests once during menstruation and
      once during the midluteal phase. The midluteal phase was determined by projection
      from day of ovulation, as verified by ovulation detection kits, and by
      confirmation of subsequent menstruation. Results revealed a significant sex
      difference for 5 of the 6 tasks. However, there was no evidence that performances
      differed with menstrual cycle phase. These results from younger women, combined
      with previous results from older women, may help establish the boundaries for
      hormonal influences on cognitive and motor-skill behavior.

PMID- 9926815
TI  - Neonatal monoaminergic depletion in mice (Mus musculus) improves performance of a
      novel odor discrimination task.
AB  - This experiment examined behavior and neurochemistry in adult mice (Mus musculus)
      after neonatal depletion of monoaminergic fibers projecting to the neocortex and
      hippocampus. Lesions were made on Postnatal Day 1; mice developed to adulthood
      and were assessed on simple odor discrimination (SOD) and odor delayed nonmatch
      to-sample (DNMS) tasks, passive avoidance (PA), and locomotor activity. On SOD,
      lesioned mice performed faster than controls but with similar accuracy. On the
      DNMS task, the lesioned mice performed faster and more accurately than controls.
      On PA, the lesioned mice exhibited a retention deficit relative to controls.
      Locomotor activity was similar in the 2 groups. Postmortem analyses revealed that
      the lesions reduced significantly norepinephrine and serotonin levels in both the
      neocortex and hippocampus. The data suggest that cortically projecting
      monoaminergic fibers play an important role in normal cognitive development.

PMID- 9926816
TI  - Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of
      inhibitory conditioning.
AB  - Exposure to a brief, stressful event is reported to facilitate classical eyeblink
      conditioning in the male rat (Rattus norvegicus) by use of a delay paradigm in
      which the conditioned stimulus (CS) and unconditioned stimulus (US) overlap and
      coterminate. This study examined the effects of stress on trace conditioning, a
      task in which the CS and US were separated by 500 ms. Experiment 1 showed that
      exposure to brief (1 s), low-intensity (1 mA) tailshocks facilitated acquisition
      24 hr later. Experiment 2 showed that stressor exposure did not affect retention
      or extinction of trace conditioning in rats that were stressed after acquisition.
      Experiment 3 showed that exposure to the same stressor opposed acquisition of
      inhibitory conditioning. These results suggest that exposure to a stressful event
      persistently facilitates acquisition of trace conditioning and enhances a bias
      toward acquiring positive versus negative associations.

PMID- 9926817
TI  - Effects of lesions of thalamic intralaminar and midline nuclei and internal
      medullary lamina on spatial memory and object discrimination.
AB  - Male Sprague-Dawley rats received either radiofrequency lesions of the lateral
      internal medullary lamina (IML) or ibotenic acid lesions of the lateral
      intralaminar nuclei (ILN) and midline nuclei (MLN) or sham treatment. Neither
      lesion group was impaired in the retention of 3 object pair discriminations
      acquired before surgery nor in the acquisition of a new object pair after
      surgery. Rats with ILN, but not IML, lesions were impaired in acquiring an
      initial and 5 subsequent hidden platform locations in a water maze task. These
      results suggest that damage to both ILN and MLN are needed to produce spatial
      learning deficits and that extensive damage to the IML or ILN has no detectable
      effects on retrograde or anterograde memory of object discriminations.

PMID- 9926818
TI  - Place memory is intact in rats with perirhinal cortex lesions.
AB  - Two experiments compared the effects of bilateral lesions of the hippocampal
      formation (HPC) or perirhinal cortex (PRh) on rats' performance of an allocentric
      spatial working memory task--delayed matching-to-place (DMTP) in a water maze.
      DMTP trials consisted of paired swims, and the hidden platform was moved to a new
      location on each trial. Performance was assessed with intervals between the first
      and second swim (i.e., retention delays) of 4, 30, 120, and 300 s. The rats
      received extensive presurgery training in Experiment 1 and no presurgery training
      in Experiment 2. In both experiments, rats with HPC lesions displayed DMTP
      deficits at all delays, taking longer and swimming farther to find the platform
      on the second swims than did sham-operated controls. By contrast, rats with PRh
      lesions displayed normal DMTP acquisition and performance. The results suggest
      that, unlike the functions of HPC, those of PRh are not critical for allocentric
      spatial working memory.

PMID- 9926819
TI  - Instrumental learning within the spinal cord: I. Behavioral properties.
AB  - Four experiments are reported that explore whether spinal neurons can support
      instrumental learning. During training, one group of spinal rats (master)
      received legshock whenever one hindlimb was extended. Another group (yoked)
      received legshock independent of leg position. Master, but not yoked, rats
      learned to maintain their leg in a flexed position, exhibiting progressively
      longer flexions as a function of training (Experiment 1). All subjects were then
      tested by applying controllable shock to the same leg (Experiment 2). Master rats
      reacquired the instrumental response more rapidly (positive transfer), whereas
      yoked rats failed to learn (a learned helplessness-like effect). Disrupting
      response-outcome contiguity by delaying the onset and offset of shock by 100 ms
      eliminated learning (Experiment 3). Experiment 4 showed that shock onset
      contributes more to learning than does shock offset.

PMID- 9926820
TI  - Postnatal choline supplementation in preweanling mice: sexually dimorphic
      behavioral and neurochemical effects.
AB  - The aim of this study was to investigate the effects of postnatal choline
      supplementation on neurochemical and behavioral parameters in preweanling
      BALB/cByJ mice. Mouse pups were injected daily subcutaneously with choline
      chloride (0.85 mM/g body weight) from Postnatal Day (PND) 1 to PND 16. Pups
      performed a passive avoidance (PA) learning task on PND 17-18 and a 30-min
      locomotor activity test on PND 19. The choline treatment affected retention of
      the PA task on PND 18. The treatment also increased locomotor activity in
      females, but not in males, on PND 19. Choline acetyltransferase (ChAT) enzymatic
      activity was measured on PND 20 and revealed that choline administration in the
      first 2 weeks of postnatal life selectively affects male pups. Choline's effect,
      as seen in previous rat experiments, was to decrease ChAT activity in the
      hippocampal region.

PMID- 9926821
TI  - Classical conditioning to hypoxia using odors as conditioned stimuli in rats.
AB  - The authors performed a differential conditioning experiment in 30 rats, using 2
      odors as the conditioned stimuli (CS+ and CS-) and hypoxia (8% O2) as the
      unconditioned stimulus. Vanillin was the CS+ and rose the CS- in half of the
      rats, and vice versa in the other half. Fifteen paired CS+/hypoxia trials and 15
      CS- only trials were performed in random order, followed by 3 CS+ only and 3 CS-
      only trials to test for conditioning. The increase in ventilation from
      prestimulus levels averaged 116 +/- 85% in response to CS+ versus 55 +/- 36% in
      response to CS-. This effect was supported by the significant Pre-Post Stimulus x
      CS Type interaction for this variable (p < .003). The data confirm the
      sensitivity of breathing to conditioning processes and also indirectly support
      the hypothesis that feedforward responses may complement feedback reflex pathways
      in respiratory homeostasis.

PMID- 9926822
TI  - Amygdala kindling-resistant (SLOW) or -prone (FAST) rat strains show differential
      fear responses.
AB  - The authors compared two rat strains, selectively bred for their susceptibility
      to amygdala kindling, with respect to their performance on various behavioral and
      learning tasks that are associated with fear and anxiety. The two rat strains
      differed significantly in measurements of exploration of novel and familiar
      environments, as well as in reactivity to footshock and fear-based learning. The
      kindling-resistant (SLOW) strain exhibited a lower ratio of open- to closed-arm
      entries in the elevated plus-maze, less activity over days in the open field,
      greater behavioral suppression in the open-field if previously footshocked,
      greater freezing in the inhibitory avoidance task, and slower acquisition and
      poorer retention in the one-way avoidance task than did the kindling-prone (FAST)
      strain. These experiments suggest that the SLOW rats are more expressively
      fearful than the FAST rats, particularly with respect to environmentally
      triggered freezing or immobility. Further, these observations imply that the
      relatively constrained excitability of the amygdala network in the SLOW rats
      might mediate their relatively greater expression of fear and anxiety compared
      with the FAST rats.

PMID- 9926823
TI  - Norepinephrine release in the amygdala after systemic injection of epinephrine or
      escapable footshock: contribution of the nucleus of the solitary tract.
AB  - Several findings based largely on lesions and drug manipulations within the
      amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to
      enhancement of memory processes by epinephrine (EPI). However, no studies to date
      have directly measured changes in the release of NE in the amygdala after EPI
      injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE
      release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and
      administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI
      produced a significant elevation in NE release that persisted for up to 60 min.
      In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl)
      into the nucleus of the solitary tract (NTS) immediately before injection of 0.3
      mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in
      Experiment I was attenuated by inactivation of the NTS. These findings indicate
      that systemic injection of EPI increases release of NE in the amygdala and
      suggest that the effects are mediated in part by activation of brainstem neurons
      in the NTS that project to the amygdala.

PMID- 9926824
TI  - Bimodal modulation by nicotine of anxiety in the social interaction test: role of
      the dorsal hippocampus.
AB  - In conditions generating moderate levels of anxiety in the social interaction
      test (low light, unfamiliar arena or high light, familiar arena), parenteral
      administration of nicotine had bimodal actions, low doses (0.01 and 0.1 mg/kg
      i.p.) had anxiolytic effects and high doses (0.5 and 1.0 mg/kg i.p.) had
      anxiogenic effects. In test conditions where anxiety was lowest (low light,
      familiar arena) and highest (high light, unfamiliar arena), nicotine was without
      effect after intraperitoneal or hippocampal administration. Thus, nicotine plays
      a modulatory role in which the activity of other neurotransmitters is crucial to
      its expression. After bilateral administration to the dorsal hippocampus,
      nicotine (0.1-8.0 microg) had anxiogenic effects in conditions of moderate
      anxiety; mecamylamine (30 ng) was silent in these conditions, indicating no
      intrinsic tone. Our results show that the dorsal hippocampus is one area that can
      mediate anxiogenic effects in the social interaction test, but the brain region
      mediating anxiolytic effects remains to be identified.

PMID- 9926825
TI  - Serotonin plays a permissive role in conditioned olfactory learning induced by
      norepinephrine in the neonate rat.
AB  - This study examined the role of serotonin (5-hydroxytryptamine; 5-HT) in
      conditioned olfactory learning in the rat pup. By injecting various combinations
      of the 5-HT(2A/2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI), and the beta adrenoceptor agonist, isoproterenol, we observed
      that isoproterenol alone acted as an unconditioned stimulus (US) to induce
      learning, as reported previously, whereas DOI alone did not induce learning. DOI
      combined with isoproterenol produced a leftward shift in the effective US dose
      such that suboptimal isoproterenol was effective, and previously optimal levels
      of isoproterenol were ineffective. Thus, 5-HT plays a facilitative but not an
      obligatory role in conditioned olfactory learning in the neonate rat.

PMID- 9926826
TI  - Olfactory function in the human fetus: evidence from selective neonatal
      responsiveness to the odor of amniotic fluid.
AB  - This study was aimed at characterizing the level of specificity of the human
      newborn's response to an odor experienced in utero. Three groups of breast-fed
      infants and 3 groups of bottle-fed infants were examined on Postnatal Day 3 for
      their differential head-turning response when exposed to paired-choice tests
      contrasting the odors of either familiar (f) amniotic fluid (AF) or nonfamiliar
      (nf) AF or either of these AF odors and a control (C) stimulus. In fAF versus
      nfAF tests, the infants oriented preferentially to the odor of fAF, regardless of
      their feeding regimen (i.e., of their postnatal reexposure to AF-like cues in
      maternal milk). The fAF or nfAF versus C tests showed that this response pattern
      was caused by a true positive orientation toward fAF and not by avoidance from
      nfAF odor. This highly selective neonatal response to fAF odor is consistent with
      the hypothesis that the human fetus can detect and store the unique chemosensory
      information available in the prenatal environment and that this information
      becomes coupled with positive control of behavior.

PMID- 9926827
TI  - Effects of isolation rearing on startle reactivity, habituation, and prepulse
      inhibition in male Lewis, Sprague-Dawley, and Fischer F344 rats.
AB  - This study compared the interaction of strain with isolation rearing on startle
      reactivity, habituation, and prepulse inhibition (PPI) in male Lewis, Sprague
      Dawley, and Fischer F344 rats tested as adults. Lewis and Fischer rats exhibited
      lower startle reactivity than Sprague-Dawley rats. Lewis rats displayed more
      rapid habituation than the other strains. Most important, isolation rearing
      produced deficits in PPI in both Sprague-Dawley and Fischer rats but had no
      effect in Lewis rats. By contrast, isolation rearing had no effect on startle
      reactivity or habituation. In a separate study, 0.5 mg/kg apomorphine disrupted
      PPI in Fischer but not in Lewis rats. Thus, PPI in Lewis rats is relatively
      unaffected by either a pharmacological or a developmental manipulation, both of
      which disrupt PPI in Sprague-Dawley and Fischer F344 rats.

PMID- 9926828
TI  - Intact neurons of the lateral habenular nucleus are necessary for the
      nonhormonal, pup-mediated display of maternal behavior in sensitized virgin
      female rats.
AB  - Our research has demonstrated that the lateral habenular nucleus (Lhb) is
      necessary for the hormonal onset but not the postpartum maintenance of maternal
      behavior in the rat (K. P. Corodimas, J. S. Rosenblatt, & J. I. Morrell, 1992; K.
      P. Corodimas, J. S. Rosenblatt, M. E. Canfield, & J. I. Morell, 1993; T. Matthews
      Felton, K. P. Corodimas, J. S. Rosenblatt, & J. I. Morell, 1995). To test the
      role of the Lhb in the nonhormonal onset of maternal behavior, we used the
      sensitization model in which the continual exposure of females to pups induces
      maternal behavior. Ovariectomized females received bilateral cytotoxic lesions of
      neurons of either the Lhb or the dorsal medial cingulate cortex-hippocampus, or
      they were unoperated. Maternal behavior, activity, and oromotor carrying
      capability were tested. Complete lesions of the neurons of the Lhb induced
      significant deficits in pup retrieval and nest building. Sniffing, licking, and
      crouching behaviors were unaltered. Activity and carrying ability were normal.
      These results indicate a role for the Lhb that extends to the nonhormonally
      dependent onset of maternal behavior, but they also indicate a more limited role
      than in the mediation of the hormonal onset of the behavior.

PMID- 9926830
TI  - Quinpirole induces compulsive checking behavior in rats: a potential animal model
      of obsessive-compulsive disorder (OCD).
AB  - Rats treated chronically with the dopamine agonist quinpirole (0.5 mg/kg, twice
      weekly x 10) met 5 criteria for performance of compulsive checking. Specifically,
      in a large open-field with single small objects in 4 of 25 locales, quinpirole
      rats revisited two places/objects excessively often and rapidly, compared with
      other locations in the environment or saline controls. They performed a ritual
      like set of behavioral acts at these two places/objects and stopped in relatively
      few locales before returning to the preferred places/objects. Finally, they
      shifted their behavior to a new location when the object was moved there.
      Clomipramine (10 mg/kg, daily) postponed but did not prevent the development of
      the quinpirole effect. Quinpirole-induced compulsive checking may be an
      exaggeration of normal checking of home site in rats. Results suggest an animal
      model of obsessive-compulsive disorder and a role for dopamine in this disorder.

PMID- 9926829
TI  - Repeated isolation stress in the neonatal rat: relation to brain dopamine systems
      in the 10-day-old rat.
AB  - Isolation of the rat pup from the nest and dam for one hour per day from PN 2-9
      is a useful paradigm for producing stress in the neonate. These previously
      isolated rats respond to an amphetamine challenge with alterations in activity at
      the juvenile stage or as adults. Furthermore, when dopamine release is measured
      in the nucleus accumbens, juveniles release 3 times more dopamine after
      amphetamine than do controls. This study describes changes in behavior and brain
      dopamine systems at PN 10. Experiment 1 determined an appropriate amphetamine
      dose that could be used for behavioral activation at PN 10. Experiment 2 produced
      significant evidence of enhanced behavioral activation after the isolation
      paradigm and indicated that brain regions innervated by the mesolimbic dopamine
      system, septum, and hypothalamus display increased dopamine turnover and that the
      nigrostriatal pathway is less active. Likewise, in Experiment 3, in vivo
      microdialysis of the nucleus accumbens indicated that previously isolated pups
      respond to an amphetamine challenge with a several-fold increase in dopamine
      release over a 4-hour session.

PMID- 9926831
TI  - Flank-marking behavior and the neural distribution of vasopressin innervation in
      golden hamsters with suprachiasmatic lesions.
AB  - In golden hamsters, microinjections of arginine-vasopressin (AVP) within the
      anterior hypothalamus trigger a stereotyped scent-marking behavior, flank
      marking. Our experiment was carried out to test the contribution of AVP neurons
      within the suprachiasmatic nucleus (SCN) in the control of this behavior. Our
      results suggest that the SCN does not contribute to flank-marking behavior.
      Whereas SCN lesions disrupted circadian rhythms of wheel running, the same
      lesions did not disrupt flank-marking. The results also suggest that neurons
      located outside the SCN contribute significantly to the vasopressinergic
      innervation of the brain and the expression of AVP-dependent behaviors, such as
      flank-marking behavior. Although AVP-immunoreactive fibers were severely (ca.
      95%) depleted from several forebrain areas in SCN-lesioned hamsters, the effect
      of the lesions was much more limited within the forebrain areas involved in flank
      marking behavior as well as within the midbrain and hindbrain.

PMID- 9926832
TI  - Functions of the caudal periaqueductal gray in lactating rats: kyphosis,
      lordosis, maternal aggression, and fearfulness.
AB  - Severe impairment of the kyphotic nursing posture in lactating rats found
      previously after prepartum lesions of the caudal intercollicular periaqueductal
      gray (cPAG-x) was confirmed and was extended to a continuous 24-hr period.
      Litters of cPAG-x dams gained approximately 10% less weight postnatally than
      controls, which was in part related to their dams' compensatory prone nursing
      posture that was ineffective for milk letdown. Sexual proceptivity and
      receptivity (lordosis) during the postpartum estrus were virtually eliminated in
      subjects with relatively large bilateral cPAG lesions. The doubling of maternal
      attacks toward a male intruder after lesioning was also confirmed and was related
      to reduced fearfulness in an elevated plus-maze. Thus, the cPAG plays a
      multifaceted role in parturient rats; it is involved in the mediation of nursing,
      sexual, aggressive, and fear behaviors.

PMID- 9926833
TI  - Sustained attention performance in rats with intracortical infusions of 192 IgG
      saporin-induced cortical cholinergic deafferentation: effects of physostigmine
      and FG 7142.
AB  - Rats with extensive lesions of cortical cholinergic afferents as a result of
      infusions of 192 IgG-saporin into the basal forebrain show persistent impairments
      in sustained attention performance (J. McGaughy, T. Kaiser, & M. Sarter, 1996).
      However, the administration of neither the cholinesterase inhibitor physostigmine
      nor the benzodiazepine receptor partial inverse agonist FG 7142 attenuated the
      lesion-induced impairments in performance. The present study demonstrated that
      less extensive cortical cholinergic deafferentation, produced by intracortical
      infusions of a relatively small concentration of 192 IgG-saporin, resulted in a
      significant impairment in sustained attention. However, the administration of
      neither physostigmine (0.01-0.1 mg/kg) nor FG 7142 (0.1-1.0 mg/kg) benefited the
      performance of the animals. Because neither compound selectively augments
      performance-associated increases in acetylcholine release from residual neurons,
      beneficial effects on cortical cholinergic deafferentation-based impairments in
      attention may remain limited.

PMID- 9926834
TI  - Contingent tolerance, compensatory responses, and physical dependence in diazepam
      treated amygdala-kindled rats.
AB  - Three groups of amygdala-kindled rats received 10 bidaily treatment trials: On
      each trial, the drug-before group received a diazepam (2.5 mg/kg i.p.) injection
      1 hr before a convulsive stimulation, the drug-after group received a diazepam
      injection 1 hr after a stimulation, and the vehicle control group received a
      vehicle injection either 1 hr before or 1 hr after a stimulation. After
      treatment, only the drug-before group displayed significantly longer forelimb
      clonus under the influence of diazepam (that is, they displayed contingent
      tolerance to diazepam's anticonvulsant effect) and significantly longer forelimb
      clonus while drug free. Following a 14-day retention period, the rats in the drug
      before group retained significant levels of contingent tolerance but did not
      display significant increases when tested drug free. These data suggest that
      compensatory responses do not play a causal role in the expression of contingent
      tolerance.

PMID- 9926835
TI  - Progesterone receptor isoforms are differentially regulated by sex steroids in
      the rat forebrain.
AB  - We studied the effects of estradiol (E2) and progesterone (P4) on expression of
      genes coding for PR isoforms in the forebrain of ovariectomized rats by RT-PCR
      analysis. In the hypothalamus the expression of both PR isoforms was induced by
      E2 and down-regulated by P4. In the preoptic area these changes were only
      observed in the PR-B isoform. In contrast, in the hippocampus PR induction by E2
      was only observed for PR-A. In this region P4 did not modify the expression of
      any PR isoform. These results indicate that PR isoforms expression is
      differentially regulated by sex steroid hormones in distinct forebrain regions
      and suggest that the tissue-specific regulation of either PR-A or PR-B may be
      involved in the physiological actions of P4 upon the rat brain.

PMID- 9926836
TI  - Cross-excitation in dorsal root ganglia does not depend on close cell-to-cell
      apposition.
AB  - About 90% of neurons in dorsal root ganglia (DRGs) of rats 2-5 weeks of age are
      depolarized and excited by impulse activity in neighboring neurons that share the
      same DRG. Synaptic contacts are extremely rare in DRGs, but instances of close
      membrane apposition between pairs of neuronal somata are not uncommon, especially
      in prenatal rats. Close membrane apposition could permit electrotonic
      interactions among neighboring DRG neurons. We carried out an ultrastructural
      examination of DRGs taken from rats 2-5 weeks of age and found that by this age <
      2% of cells remain in close apposition with neighbors. The remainder are
      separated by one or two layers of satellite glial cytoplasm. It is, therefore,
      unlikely that close apposition between adjacent neurons contributes significantly
      to functional cross-excitation in the DRG.

PMID- 9926837
TI  - Perception of timing of kinesthetic stimuli.
AB  - A psychophysical method was used to estimate the timing of perception of
      kinesthetic stimuli with different velocities in normal volunteers. A 1 ms
      auditory click occurred randomly before or after an imposed flexion movement at
      either 20, 40 or 60 deg/s of the metacarpophalangeal joint. Subjects reported
      whether the click was perceived before or after the movement onset (experiment 1)
      or perception of movement velocity (experiment 2). The time at which there was a
      50% chance that subjects reported movement or velocity perception after the click
      was taken as an estimate of the time subjects perceived the stimuli. The
      difference in time of perceived movement velocity discrimination and movement
      onset was only significant when the velocity was 20 deg/s (52 ms). This suggests
      that movement onset and identification of the velocity of the faster movements
      are perceived nearly simultaneously.

PMID- 9926838
TI  - Dipole source localization of ictal epileptiform activity.
AB  - Dipole source localization of ictal epileptiform activity recorded by scalp EEG
      was performed in patients prior to surgical treatment. The dipole tracing method
      combined with the scalp-skull-brain head model was used to locate epileptogenic
      foci. A digital EEG system was used for data collection. The accuracy of dipole
      source localization was evaluated by comparing the focus location with that
      obtained by chronic subdural electrocorticography. In a case of frontal lobe
      epilepsy with epileptogenic focus in the frontoparietal convexity, the results of
      dipole source localization agreed well with those obtained with chronic subdural
      electrocorticography. In a case of lateral temporal lobe epilepsy, the results of
      dipole source localization were consistent with those obtained with chronic
      subdural electrocorticography, but a small localization error was observed. The
      clinical usefulness of and suggestions for improving this method are discussed.

PMID- 9926839
TI  - APE/Ref-1 responses to ischemia in rat brain.
AB  - Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic
      sequence of events that can trigger oxidative stress response cascades in neurons
      of the central nervous system. After transient ischemia there is an increase in
      intracellular Ca2+ release, extracellular glutamate, reactive oxygen species
      (ROS) and nitric oxide, genotoxic events that stimulate DNA repair. Increased
      oxidative stress and interrupted blood flow in ischemia, like DNA repair, also
      deplete cellular ATP and commit neurons to apoptosis. We report that levels of
      the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) decreased
      significantly in the hippocampus but not other brain areas after 6 h of
      reperfusion following an induced ischemic insult. This specific inhibition of
      APE/Ref-1 expression may affect the extent of apoptosis after ischemia.

PMID- 9926840
TI  - Absence of increased hypothalamic nitric oxide synthase gene expression during
      the preovulatory LH surge in middle-aged rats.
AB  - This study was performed to test the hypothesis that diminution in the
      preovulatory luteinizing hormone (LH) surge in middle-aged (MA) rats may be
      related to altered activity in nitric oxide (NO)ergic neurons. To begin to test
      the hypothesis, gene expression of hypothalamic NO synthase (NOS), the enzyme
      that catalyzes NO production, was examined on the day of proestrus in young (2-3
      months old) and middle-aged (MA, 8-10 months old) rats. Compared with those at
      10.00 h, NOS mRNA levels were increased significantly at 12.00 h and the LH surge
      occurred at 16.00 h in young rats. In MA rats, in contrast, there was no change
      in NOS mRNA levels between morning and afternoon hours in association with a
      delayed and attenuated LH surge. These results show that hypothalamic NOS gene
      expression increases long before the LH surge in young rats and that this
      antecedent increase in NOS gene expression does not occur in MA regularly cycling
      rats. Since hypothalamic NOergic neurons participate in induction of LH-releasing
      hormone (LHRH) and LH surges, our results suggest that reduced LH surges in MA
      rats may, in part, be due to altered NOS neuronal activity in these animals.

PMID- 9926841
TI  - Learning-induced expansion of cortical maps--what happens to adjacent cortical
      representations?
AB  - The present study was designed to investigate the effects of learning-dependent
      enlargement of cortical representation of a row of vibrissae upon the appearance
      of adjacent cortical representations. We have found previously that three
      sessions of classical conditioning, during which stimulation of row B of
      vibrissae is paired with a tail shock, result in an increase of cortical
      representation of the trained row, as visualized with 2-deoxyglucose (2DG)
      metabolic functional mapping. In the present experiment, after the training in
      which row B was stimulated, we mapped with 2DG the cortical representations of
      rows A and C, not stimulated during the training. We found that these
      representations do not differ from normal. Because of expansion of cortical
      representation of the trained row, the overlap between representations of
      neighboring rows of vibrissae became greater and the two maps co-existed within
      the same cortical space.

PMID- 9926842
TI  - Metabotropic glutamate receptor in vasopressin, CRF and VIP hypothalamic
      neurones.
AB  - The excitatory amino acid glutamate, acting via ionotropic and metabotropic
      glutamate receptors, appears to play an important role in the control of
      neuroendocrine functions. The aim of the present investigations was to determine
      whether hypothalamic neurones which synthesize arginin-vasopressin (AVP), CRF and
      VIP express metabotropic glutamate receptor (mGluR). Double-label
      immunocytochemistry and the mirror technique were used. We found that AVP
      immunoreactive neurones of the paraventricular, supraoptic and suprachiasmatic
      nuclei contain mGluR1a, but the number of double-labelled neurones was different
      in the three cell groups. mGluR1a was present in a significant number of
      paraventricular CRF nerve cells, and in almost all VIP neurones of the SCHN.
      These results support the view that the excitatory transmitter glutamate may
      directly influence AVP, CRF and VIP neurones of the three hypothalamic cell
      groups.

PMID- 9926843
TI  - Potent suppressive effects of urocortin on splenic lymphocyte activity in rats.
AB  - To assess the possible role of urocortin, a recently identified neuropeptide
      related to corticotropin-releasing factor (CRF), in modulation of peripheral
      immune functions, the effects of intracranially administrated urocortin on the
      proliferative activity of splenic lymphocytes were examined in rats.
      Intracerebroventricular (i.c.v.) injection of urocortin (1 ng) produced a marked
      decrease in the proliferative response of splenocytes to a mitogen. The
      suppressive effect of urocortin was abolished by pretreatment with a ganglionic
      blocking agent (chlorisondamine) or a beta-adrenergic receptor antagonist
      (propranolol), but not by adrenalectomy. These results suggest that urocortin is
      an important neuropeptide involved in the brain control of peripheral immune
      functions such as stress-induced immunosuppression, and that the suppressive
      effect of urocortin is mediated by the sympathetic nervous system.

PMID- 9926844
TI  - Elevation of melatonin in chicken retina by 5-hydroxytryptophan: differential
      light/dark responses.
AB  - Melatonin is synthesized in the chicken retina under the influence of a circadian
      clock, which also regulates the expression of tryptophan hydroxylase (TPH) and
      serotonin N-acetyltransferase (AA-NAT). In order to examine the role of substrate
      supply in the rhythmic synthesis of melatonin in chicken retina, tryptophan and 5
      hydroxytryptophan were administered day and night in light or darkness. When
      administered systemically at night in darkness, 5-hydroxytryptophan, but not
      tryptophan, dramatically stimulates melatonin levels in the chick retina in a
      dose-dependent manner. Intraocular administration of 5-hydroxytryptophan also
      increases melatonin levels locally, indicating a retinal site of action of the
      serotonin precursor. The effect of 5-hydroxytryptophan is much greater at night,
      when TPH and AA-NAT activities are high, than during the day, when the enzyme
      activities are low. Similarly, unexpected light exposure at night, which
      inactivates AA-NAT, significantly reduces the ability of 5-hydroxytryptophan to
      increase retinal melatonin levels. The results suggest that TPH, but not AA-NAT
      or other enzymes in the melatonin biosynthetic pathway, is saturated with
      substrate in situ. The rate of melatonin production appears to be a function of
      the concentration of serotonin, which is regulated by TPH, and by the level of
      activity of AA-NAT.

PMID- 9926845
TI  - NMDA antagonist displays anticonvulsant effect via NO synthesis inhibition in
      penicillin-treated rat hippocampal slices.
AB  - The present study investigated the role of nitric oxide (NO) in epileptogenesis
      and whether this role correlated with ionotropic glutamate receptor (IGR). Using
      a self-constructed NO-sensitive microelectrode (SNM), we observed the effect of
      nitric oxide synthase (NOS) inhibitors, NMDA and non-NMDA selective antagonists
      on penicillin(PEN)-treated hippocampal slices by simultaneously recording evoked
      field potentials and nitric oxide release from CA1 pyramidal neurons. 7
      nitroindazole (7-NI),Nomega-nitro-L-arginine (L-NNA) and DL-2-amino-phospho
      novaleric acid (APV), but not 6,7-dinitroquinoxaline-2,3 (1h,4h)-dione(DNQX),
      depressed NO release and partly reversed PEN's epileptogenetic effect, while APV
      + 7-NI + L-NNA did not display a further inhibitory effect. These findings
      suggest both NOS inhibitor and NMDA antagonist involve as anticonvulsant factors
      in epileptogenesis, providing direct evidence for NO release in response to NMDA
      receptor activation. The anticonvulsant effect of NMDA antagonist may ascribe to
      its action on NO release.

PMID- 9926846
TI  - NO production during neuronal cell death can be directly assessed by a chemical
      reaction in vivo.
AB  - The role of nitric oxide (NO) as a putative mediator of neuronal death can be
      understood best if NO is detected directly. For this purpose, we developed a new
      sensitive method that for the first time directly captures released NO during
      neurodegeneration in vivo and at the cellular site of its generation. The non
      fluorescent substance 1,2-diaminoanthraquinone (DAA) was injected into the eyes
      of rats whose optic nerve was injured to induce retrograde degeneration of the
      ganglion cells. The reaction product of DAA with NO is a triazole with red
      fluorescence. The two major NO producing cell populations in the retina are
      capillary endothelial cells and microglial cells. The methodology of NO
      assessment is convenient and applicable to numerous living systems both in vivo
      and in vitro.

PMID- 9926847
TI  - Nuclear proteins from liver and kidney bind a 37 bp sequence in the 5' upstream
      region of the mGAT1 gene.
AB  - The mouse GABA transporter (mGAT1) gene has been shown to be exclusively
      expressed in brain by Northern and Western blot analyses. The interactions
      between the 5' flanking region of the mGAT1 gene and nuclear proteins from
      different mouse tissues were studied by means of gel-shift assay. Our results
      show that nuclear protein factors from non-nervous tissues can specifically
      recognize a 37 bp sequence that is conserved in the 5' flanking region between
      the human and mouse GAT1 genes. Similar nuclear protein factors were also found
      to exist in rat, rabbit and pig.

PMID- 9926848
TI  - Melatonin receptor subtype expression in human cerebellum.
AB  - We report the distinct cellular distribution in the human cerebellar cortex of
      the mammalian mt1 (Mel1a) and MT2 (Mel1b) (1) melatonin receptor subtypes.
      Specific binding of the non-selective radioligand 2-[125I]iodomelatonin to the
      outer molecular layer was significantly higher than to the granule cell layer.
      Melatonin receptor subtype expression was assessed by in situ hybridization using
      selective and specific digoxigenin-labeled antisense oligonucleotide probes. This
      is the first demonstration of MT2 melatonin receptor mRNA expression in human
      cerebellar Bergmann glia and astrocytes. On the other hand, the mt1 melatonin
      receptor mRNA was expressed in both basket-stellate cells and granule cells. We
      conclude that mt1 and MT2 melatonin receptors are heterogeneously expressed in
      human cerebellar cortex.

PMID- 9926849
TI  - Hypothalamic insulin and neuropeptide Y in the offspring of gestational diabetic
      mother rats.
AB  - The offspring of diabetic mothers is at increased risk to develop obesity and
      diabetogenic disturbances during life. Pathophysiological mechanisms responsible
      are unclear. Neuropeptide Y (NPY) is an important hypothalamic stimulator of food
      intake and body weight gain, and its levels are decreased by elevated insulin. In
      neonatally hyperinsulinaemic offspring of diabetic mother rats, hypothalamic
      insulin level was significantly increased at birth (p < 0.01). At weaning, i.e.
      at the end of the critical hypothalamic differentiation period, a significantly
      increased number of NPY-positive neurons (p < 0.01) appeared in the arcuate
      hypothalamic nucleus. In conclusion, an increase in the number of NPYergic
      neurons in the hypothalamus, possibly due to hypothalamic malformation and/or
      perinatally acquired hypothalamic insulin resistance, might contribute to the
      development of obesity and metabolic disturbances in the offspring of diabetic
      mothers.

PMID- 9926850
TI  - Injury selectively down-regulates the gene encoding for the Id4 transcription
      factor in primary cultures of forebrain astrocytes.
AB  - Astrogliosis is an important component of the response to injury of the central
      nervous system (CNS). The Id family of helix-loop-helix (HLH) transcription
      factors has been implicated in the regulation of cellular differentiation in
      several different lineages and may contribute to the regulation of astrogliosis.
      We examined the expression of Id genes in primary cultures of mouse forebrain
      astrocytes under experimental conditions in which astrogliosis was elicited by
      mechanical injury. Astrocyte cultures expressed the four known members of the Id
      gene family, Id1, Id2, Id3, and Id4. After injury, at a time when astrocytes
      developed the characteristic phenotypic changes of astrogliosis, Id4 expression
      decreased dramatically. Id1, Id2, and Id3 mRNA levels did not change. These
      results identify Id4 as a candidate marker of astroglial activation in culture
      and suggest that Id4 expression plays a role in the process of astrogliosis.

PMID- 9926851
TI  - Regulated expression of dual specificity protein phosphatases in rat brain.
AB  - Activated mitogen-activated protein (MAP) kinases play an essential role
      controlling many neuronal functions. Dual specificity protein phosphatases (DS
      PTPs) elicit selective inactivation of MAP kinases and are under tight
      transcriptional control. We have studied expression of four DS-PTPs (MKP-1, MKP
      X, MKP-3 and B23) in rat brain and examined changes during post-natal development
      and following kainic acid induced seizure activity. In normal adult brain these
      DS-PTPs exhibit a strikingly different expression pattern. Only MKP-1 was
      regulated during development with levels increased transiently (P15-P21) within
      the thalamus and somatosensory cortex. Following kainate treatment, MKP-1, MKP-3
      and B23 all exhibit striking changes in expression within hippocampal subfields
      CA1-3 and dentate gyrus. Regulated transcription of DS-PTPs may play a critical
      role controlling MAP kinase dependent processes including synaptic remodeling and
      neuronal death.

PMID- 9926852
TI  - LTP occludes the interaction between arachidonic acid and ACPD and NGF and ACPD.
AB  - We compared the interaction between the metabotropic glutamate receptor agonist
      ACPD and arachidonic acid with the interaction between ACPD and nerve growth
      factor (NGF) on presynaptic function in hippocampus. ACPD interacted with both
      NGF and arachidonic acid to increase KCl-stimulated endogenous glutamate release
      and calcium concentration in synaptosomes prepared from whole hippocampus and
      synaptosomes prepared from untetanized dentate gyrus. The data indicate that
      prior induction of long-term potentiation (LTP) in perforant path granule cells
      synapses occluded the interaction between ACPD and both NGF and arachidonic acid,
      suggesting that these agents may play a role in the generation of LTP in dentate
      gyrus.

PMID- 9926853
TI  - Fibroblast growth factor receptor expression in outer hair cells of rat cochlea.
AB  - Fibroblast growth factors (FGFs) are critical for normal development of the organ
      of Corti, and may also protect hair cells from ototoxic damage. Four different
      fibroblast growth factors are known, three of which have different splice
      variants in the extracellular immunoglobin-like (Ig) III FGF-binding domain,
      giving different patterns of sensitivity to the different FGFs. Analysis of a
      cDNA library of rat outer hair cells by the polymerase chain reaction, using
      isoform specific primers, showed expression only of FGF receptor 3, splice
      variant IIIc. This allows us to predict the pattern of sensitivity to applied
      FGFs, which may be useful in targeting outer hair cells selectively during an FGF
      based strategy for cochlear therapy.

PMID- 9926854
TI  - Tyrosine kinases are required for IFN-gamma-induced growth of human embryonic
      forebrain astrocytes.
AB  - The cytokine IFN-gamma was shown to regulate growth and differentiation of human
      embryonic forebrain astrocytes. This work investigated a signalling pathway used
      by IFN-gamma during the process of growth regulation of human fetal astrocytes
      obtained from first trimester embryos. IFN-gamma induced significantly higher
      cell survival compared to that of unexposed cultures, and this survival could be
      suppressed by incubation with the tyrosine protein kinase (TPK) specific
      inhibitor tyrphostin A47 at the non-toxic concentration of 10(-6) M. The signal
      transducer and activator of transcription (STAT)-1 was translocated into the
      nucleus upon IFN-gamma stimulation, which was also blocked by incubation with
      A47. Our data demonstrate that TPKs are actively involved in growth regulation of
      the developing brain astrocytes induced by IFN-gamma.

PMID- 9926856
TI  - Interaction between paired-pulse facilitation and long-term potentiation in the
      projection from hippocampal area CA1 to the subiculum.
AB  - Studies of the interaction between long-term potentiation (LTP) and paired-pulse
      facilitation (PPF) may throw light on the role of presynaptic factors in LTP. We
      examine here, for the first time, the nature of PPF in the CA1-subiculum
      projection. PPF peaks at a 50 ms interstimulus interval (ISI) and is evident at
      ISIs from 10 to 500 ms. There is no PPF effect at a 1000 ms ISI. PPF decreases in
      magnitude post-LTP induction across the middle range of ISI values tested (30, 50
      and 100 ms). There is a positive correlation between initial PPF values and LTP;
      this correlation increases as the ISI increases. Initial values and the change in
      PPF post-LTP are also negatively correlated.

PMID- 9926855
TI  - Odorant receptor gene expression in catfish taste tissue.
AB  - Odorant receptor expression has been reported in a variety of non-olfactory cells
      and tissues in several animal models. We therefore investigated the possible
      expression of odorant receptor genes in taste tissue of channel catfish. Multiple
      odorant receptor transcripts were amplified by PCR from barbel. In situ
      hybridization showed that receptors amplified from taste tissue, as well as
      receptors amplified from olfactory neurons, hybridized to taste epithelium with
      similar patterns. These results show that odorant receptor transcripts are
      expressed in catfish taste tissue. Taken with previous data, these results
      suggest that some members of the odorant receptor superfamily may mediate various
      chemoreceptive roles in non-olfactory cells.

PMID- 9926857
TI  - Blockade of subthalamic dopamine D1 receptors elicits akinesia in rats.
AB  - The role of dopamine in the subthalamic nucleus to control motor behaviour was
      investigated in rats using bilateral microinfusions of the dopamine D1 receptor
      antagonist SCH23390 and the dopamine D2 receptor antagonist S(-)-sulpiride.
      Selective blockade of subthalamic D1 receptors, but not of D2 receptors, produced
      catalepsy. These findings suggest that dopamine D1 receptors within the
      subthalamic nucleus play a prominent role in the regulation of motor functions.
      Furthermore, the data point to the possibility that a reduced dopaminergic tone
      at subthalamic dopamine D1 receptors might contribute to akinesia in Parkinson's
      disease.

PMID- 9926858
TI  - Vestibular ganglion neurons survive the loss of their cerebellar targets.
AB  - Neuronal survival during mammalian development crucially depends on target
      derived neurotrophic factors. Target loss removes this trophic support and leads
      in most cases to the transsynaptic retrograde degeneration of the respective
      afferents. Primary vestibular afferents (PVA) originating from bipolar neurons in
      the vestibular ganglion (VG) are the first mossy fibers that enter the
      cerebellum, but little is known about the survival requirements of VG neurons. In
      the present study the influence of the differential granule cell (GC) target loss
      on the survival of VG neurons was studied quantitatively using unbiased
      stereological methods in the cerebellar mutants Purkinje cell degeneration
      (pcd/pcd), Lurcher (Lc/+), and Weaver (wv/wv). Neither the secondary GC loss in
      the Purkinje cell deficient mutants pcd/pcd and Lc/+, nor the primary loss of GCs
      in wv/wv produced any significant reduction in the total number of bipolar
      neurons in the VG compared to controls. So, PVA neurons are highly resistant to
      cerebellar target deprivation and survive in the absence of cerebellar granule
      and Purkinje cells, regardless of whether the target loss occurs before (in
      wv/wv), during (in Lc/+) or after (in pcd/pcd) the mossy fiber-granule cell
      synaptogenesis.

PMID- 9926859
TI  - Melatonin increases striatal dopaminergic function in 6-OHDA-lesioned rats.
AB  - The purpose of this study was to assess the in vivo effects of melatonin, as an
      antioxidant, on striatal dopaminergic function in rats with a unilateral 6
      hydroxydopamine (6-OHDA) lesion of the striatum. Compared with sham-operated
      controls and expressed as a ratio relative to the contralateral side, there was
      an increase in the lipid peroxidation product malondialdehyde (MDA, 142%) and a
      significant reduction in tyrosine hydroxylase (TH) enzyme activity (28%) and
      dopamine (DA, 32%) and its metabolite dihydroxyphenylacetic acid (DOPAC, 50%) 2
      weeks after 6-OHDA injection. Melatonin treatment almost completely restored MDA
      levels to normal, suggesting the in vivo action of melatonin as an antioxidant.
      In parallel, partial, but statistically significant recovery of striatal
      dopaminergic function, including TH enzyme activity and DA levels, also occurred
      following melatonin treatment. Taken together with our previous reports showing
      behavioral and histochemical effects of melatonin on the nigrostriatal
      dopaminergic system, the present results strongly support the hypothesis that
      melatonin, as an antioxidant, may have beneficial effects on therapeutic
      approaches for the treatment of oxidative stress-induced neurodegenerative
      disease such as Parkinson's disease (PD).

PMID- 9926860
TI  - Asymmetries of representation in the visual system of pigeons.
AB  - Although functional asymmetries in the course of visual information processing
      have been known for a long time in humans as well as in non-human species, the
      structural basis of these asymmetries is largely unknown. We now report that due
      to an asymmetry of commissural projections in the pigeon the left nucleus
      rotundus of the ascending tectofugal visual system predominantly represents
      inputs from both eyes while the right nucleus rotundus mainly represents the
      contralateral left eye. We suggest that a comparable organization exists for
      several asymmetries in humans. A representation of both hemifields can provide
      the dominant hemisphere with direct access to all stimulus features when objects
      cross the vertical meridian.

PMID- 9926862
TI  - Androgen receptor immunoreactivity is present in primary sensory neurons of male
      rats.
AB  - We have examined the distribution of androgen receptor (AR) immunoreactivity in
      L6 and S1 dorsal root ganglia of male rats in order to determine whether the
      sensory component of reflex circuits is likely to be androgen-sensitive. Nuclear
      AR immunoreactivity was present in almost half of the neurons, but was decreased
      markedly by castration; after castration nuclear staining was absent and a few
      neurons showed dim cytoplasmic staining. Of the neurons possessing AR, half also
      contained calcitonin gene-related peptide (CGRP); in turn, > 80% of CGRP neurons
      contained AR. AR staining was present in both large and small CGRP neurons. This
      study shows that testosterone is likely to influence many sensory neurons and may
      therefore play an important role in modulating visceral and somatic reflexes.

PMID- 9926861
TI  - Neuroprotection with Bcl-2(20-34) peptide against trauma.
AB  - We tested the neuroprotective potential of the Bcl-2(20-34) peptide sequence in
      hippocampal slices. Treatment with Bcl-2 after fluid percussion trauma
      significantly improved recovery of CA1 antidromic PS to a mean of 92%+/-1 of
      initial amplitude, compared with only 16%+/-2 in unmedicated slices. The EC50 for
      trauma protection was 84 microM Bcl-2(20-34). Protection with Bcl-2(20-34) also
      extended to long-term potentiation. No protection was seen with the reverse
      sequence of Bcl-2(20-34). Treatment with Bcl-2(20-34) also protected against
      hypoxic damage, with treated slices recovering to 98%+/-2, while unmedicated
      slices recovered to 14%+/-2. Similar protection was seen against AMPA, NMDA and
      nitric oxide. These findings indicate that Bcl-2(20-34) provides specific
      neuroprotection against acute CA1 neuronal injury.

PMID- 9926863
TI  - Magnesium plus mexiletine inhibit energy usage and protect retinas against
      ischemia.
AB  - We determined whether exogenous Mg2+ and/or mexiletine (Mex), which are reported
      to be neuroprotective agents, reduced neuronal energy requirements and protected
      against ischemia, using isolated rabbit retinas. Under non-ischemic conditions,
      Mex (300 microM) and the combination of Mg2+ (1 mM) plus Mex (300 microM)
      significantly reduced glucose utilization, by 19% and 31%, respectively. The
      combination of Mg2+ plus Mex, but not either agent alone, significantly reduced
      lactate production (by 18%; p < 0.05). When added during 2 h of ischemia
      (simulated by the reduction of oxygen from 95% to 15% and of glucose from 6 mM to
      1 mM), Mg2+ plus Mex improved the recovery of glucose utilization (p < 0.01),
      lactate production (p < 0.05) and neuronal function (p < 0.05) for 3 h following
      return to control (post-ischemia/recovery) conditions. Thus reducing energy
      demands by blocking functions during temporary ischemia, protects neurons from
      irreversible functional damage.

PMID- 9926864
TI  - Skin cooling attenuates rat dorsal horn neuronal responses to intracutaneous
      histamine.
AB  - Itch sensation is reduced by cooling the skin. We tested whether lowering skin
      temperature attenuates responses of spinal dorsal horn neurons elicited by
      intracutaneous (i.c.) microinjection of histamine in anesthetized rats. Cooling
      the skin to 3 degrees C significantly and reproducibly reduced (to a mean of 48%)
      i.c. histamine-evoked responses in 20 of 24 wide dynamic range-type dorsal horn
      neurons. Histamine-evoked responses recovered to control levels after rewarming
      the skin. Assuming that such neurons play a role in signaling itch, depression of
      their responses during skin cooling may account for the psychophysical
      observation that skin cooling relieves itch in humans.

PMID- 9926865
TI  - Severe pathological changes of parabrachial nucleus in Alzheimer's disease.
AB  - In the first of a series of studies aimed at mapping brain stem pathological
      changes in patients with Alzheimer's disease (AD), we report a new finding
      regarding the parabrachial nucleus (PBN), a unit of paramount importance in the
      relay and integration of visceral and nociceptive information as well as in
      homeostatic control. The brains of 20 patients with AD were surveyed. The PBN
      contained pervasive neuropathological changes in 100% of the brains from those
      with early-onset dementia and in 80% from those with late-onset dementia. These
      changes were entirely absent in all 10 normal controls. The pathological changes
      of PBN, would cause autonomic dysfunction in patients with AD and perhaps
      contribute to the disproportionate mortality encountered in these patients.

PMID- 9926867
TI  - Expression of alphaB-crystallin in a mouse model of inherited retinal
      degeneration.
AB  - AlphaB-crystallin, which is abundantly expressed in the lens but also in a
      diversity of other tissues, functions as a stress-inducible molecular chaperone
      and is increased in brain neurodegenerative diseases. We compared retinal alphaB
      crystallin expression in a model of inherited retinal degeneration, the rd mouse,
      and controls. Northern and in situ hybridization analysis showed alphaB
      crystallin mRNA to have an altered spatio-temporal pattern with increased levels
      localized to glial cells in the degenerative state. Immunocytochemistry confirmed
      increased expression at Muller cells and astrocytes, together with transiently
      increased localization to the degenerating photoreceptors. These findings suggest
      that increased alphaB-crystallin expression is associated with glial cell
      reaction to neuronal damage in the retina, and may comprise part of the retina's
      overall defensive response to the stress of apoptotic photoreceptor cell death.

PMID- 9926868
TI  - Predictability of stimulus deviance and the mismatch negativity.
AB  - The purpose of this study was to test the previous report that generation of the
      mismatch negativity (MMN) component of event-related brain potentials (ERPs) is
      indifferent to the predictable occurrence of stimulus deviance. A pattern of
      standards (S) and deviants (D) were delivered in a predictable fashion (SSSSD) at
      two different speeds (1.3 s and 100 ms). An MMN was obtained to the D position
      tone at the slow but not the fast pace. These results demonstrate that, unlike
      the P3 component, the MMN is sensitive to the predictable occurrence of stimulus
      deviance when the predictability can be detected by the brain within the
      estimated limits of sensory memory.

PMID- 9926866
TI  - Bcl-x and Bcl-2 immunoreactivity in postnatal mouse barrel fields.
AB  - BcL-xL and Bcl-2 proteins were identified by paraffin section
      immunohistochemistry in the neuropil core of the barrelettes of the caudalis
      spinal trigeminal nucleus 6 h after birth. They were subsequently identified at
      progressively more rostral levels of the trigeminal pathway, peaking in barreloid
      neuropil cores in the ventral posterior thalamic nucleus at postnatal day (P)4.5,
      and in cortical barrel cores at P7. Labelling was confined to the cores of barrel
      like structures surrounded by immunonegative shells and became progressively less
      distinct at all levels from P8. These protein products, which are usually
      considered to control the onset of apoptosis, may serve other functions in the
      axon terminal fields of the trigeminal pathway.

PMID- 9926869
TI  - A powerful GABA(B) receptor-mediated inhibition of GABAergic neurons in the
      arcuate nucleus.
AB  - We combined histofluorescence with in situ hybridization to identify GABAergic
      neurons in the arcuate nucleus (ARC) following electrophysiological recordings,
      using GAD65 as a marker. Intracellular recordings were made in hypothalamic
      slices prepared from ovariectomized guinea pigs. Over 90% of ARC neurons tested
      with the GABA(B) receptor agonist baclofen responded with a membrane
      hyperpolarization or an outward current. The hyperpolarization was dose
      dependent, and the GABA(B) receptor antagonist CGP 35,348 produced a rightward
      shift in the agonist dose-response curve. Agonist potency was lower, and the
      efficacy greater, in GAD-positive neurons. The use of this novel technique for
      identifying GABAergic neurons thus reveals differences in the pharmacodynamics of
      GABA(B) receptor activation GABAergic and non-GABAergic ARC neurons.

PMID- 9926870
TI  - Representation of nociceptive stimuli in primary sensory cortex.
AB  - Using fMRI, we observed cortical activity associated with nociceptive hot and
      cold sensations applied to hand and foot that are not spatially restricted to the
      corresponding regions of the primary somatosensory cortex (SI). Hot (55-57
      degrees C) and cold (0-2 degrees C) tactile stimuli were applied separately to
      the right hand and foot of eight right-handed subjects. Although somatotopic
      mapping of hand and foot was observed as expected based on the Penfield
      homunculus, activations associated with hot during both hand and foot stimulation
      and subsequently, cold, activated regions unique to each thermal modality
      irrespective of the body part. This distributed system for thermal information is
      present at both nociceptive and more neutral thermal intensities (i.e. warm and
      cool sensations) indicating the presence of distributed sensory processing
      associated with thermal-related sensations in human primary sensorimotor cortex.

PMID- 9926871
TI  - Contribution of GABA(A)-mediated conductances to anoxia-induced depolarization.
AB  - CA1 pyramids were studied intracellularly in rat hippocampal slices to establish
      the contribution of excitatory amino acid (EAA) and GABA(A) receptors to the
      depolarizations induced by brief (< 10 min) anoxic episodes. An increase of the
      amplitude of the depolarizations evoked by successive anoxic episodes occurred
      with KCl (n=4 cells), not with K-acetate-filled (n=3) recording electrodes.
      Moreover, with K-acetate-filled electrodes the anoxic depolarization amplitude
      was reduced, but not abolished by EAA receptor antagonists (n=14). The residual
      anoxic depolarizations were blocked by a GABA(A) receptor antagonist (n=5) and
      decreased by the carbonic anhydrase inhibitor acetazolamide (n=4). We conclude
      that the anoxic depolarizations generated by CA1 pyramids are caused by the
      activation of EAA along with GABA(A) receptors leading to an increased membrane
      conductance to both Cl- and HCO3-.

PMID- 9926872
TI  - The putative cognitive enhancer KA-672.HCl is an uncompetitive voltage-dependent
      NMDA receptor antagonist.
AB  - KA-672.HCl (KA-672) is a new substance demonstrating anti-dementia properties. It
      shows modulatory effects on several neurotransmitter systems known to be affected
      in patients with Alzheimer's disease. In this study the action of KA-672 on the
      NMDA receptors was examined by applying patch clamp techniques to acutely
      isolated hippocampal neurons. KA-672 antagonizes NMDA responses in a voltage
      dependent manner. At a holding potential of -90 mV the IC50 value for the
      blocking action of KA-672 was 20+/-7 microM. This action of KA-672 is independent
      on the concentration either of agonist or coagonist of NMDA receptor. Ketamine,
      which interacts with the PCP center, does not occlude the action of KA-672.
      Evidently, KA-672.HCl is a weak NMDA receptor-operated channel blocker. This
      property may account for its pharmacological profile.

PMID- 9926873
TI  - Partial lithium-associated protection against apoptosis induced by C2-ceramide in
      cerebellar granule neurons.
AB  - Primary cultures of cerebellar granule neurons, maintained in a serum-containing
      medium, underwent apoptosis when exposed to C2-ceramide, as assessed by
      mitochondrial reduction of MTT and intranucleosomal DNA fragmentation. After an
      18 h exposure to 50 microM C2-ceramide, cell viability decreased by 25-40%.
      Addition of lithium together with C2-ceramide resulted in a partial protection of
      apoptosis, which was maximal at 5 mM lithium (37% protection). When lithium was
      added 5 h before the apoptotic stimulus the neuroprotective effect of the ion was
      clearly increased (66% protection). This effect was not due to intracellular
      inositol depletion or inhibition of NMDA receptors. Our data broaden the nature
      of apoptotic insults being reversed by lithium, stressing the neuroprotective
      effects of the ion.

PMID- 9926874
TI  - State-dependent impairment in object recognition after hippocampal NOS
      inhibition.
AB  - In the present study we investigated the consequences of hippocampal nitric oxide
      synthase (NOS) inhibition on the performance in an object recognition task in
      rats. In a first study we injected Nomega-nitro-L-arginine (L-NA) into the
      hippocampus directly after the first trial. One hour later the discrimination
      performance of the animals was assessed. It was found that 10 microg and 30
      microg, but not 3 microg, L-NA impaired the performance of the rats. In a second
      study in which we injected L-NA 45 min before the first trial no effects of
      treatment (10 microg and 30 microg) were observed. Since treatment with 30 microg
      has been found to inhibit hippocampal NOS almost completely and lasts longer than
      2 h, it was concluded that hippocampal NOS inhibition induced a state-dependent
      performance deficit. Consequently, studies that examine the effects of NOS
      inhibition on cognitive functions should take this confounding effect into
      account.

PMID- 9926875
TI  - Modafinil prevents glutamate cytotoxicity in cultured cortical neurons.
AB  - The ability of modafinil (Modiodal) to protect cortical neurons from glutamate
      induced degeneration was evaluated by measuring electrically evoked [3H]GABA
      release and [3H]GABA uptake in primary cerebral cortical cultures. In normal
      cells, electrical stimulation (10 Hz, 2 min) increased [3H]GABA release (FR-NER
      St1 = 0.77+/-0.14; St2/St1 ratio = 0.94+/-0.02). The exposure of sister cells to
      glutamate, reduced electrically evoked [3H]GABA release (FR-NER St1 = 0.40+/
      0.05; St2/St1 ratio = 0.60+/-0.08). Modafinil (0.3-1 microM) prevented the
      glutamate-induced reduction of the St2/St1 ratio (0.85+/-0.11; 0.88+/-0.05,
      respectively). A similar protective effect was observed for [3H]GABA uptake.
      These findings suggest that modafinil may be neuroprotective in that it
      attenuates glutamate-induced excitotoxicity in cortical neurons.

PMID- 9926876
TI  - Maternal-fetal transfers: indications, appropriateness, and cost.
AB  - The objective of this study was to assess the indications, appropriateness, and
      cost of maternal-fetal transfers to a tertiary care facility in an era of managed
      care. Our perinatal database was reviewed from January 1, 1996 through June 30,
      1997 to determine maternal and fetal indications for transfer, referring
      institution characteristics, utilization of tertiary level services, and cost of
      transfer. There were 273 transfers from 53 referring hospitals ranging in
      distance from <20 miles (n = 102) to >100 miles (n = 41). Thirty-one patients
      were transferred by air (average cost $7656), 238 by ground (average cost $920),
      4 by private car. The referring diagnosis was preterm premature rupture of
      membranes (PPROM) (n = 80), preterm labor (n = 76), preeclampsia (n = 42),
      medical complications (n = 25), or other (n = 50). Mean gestational age (GA) at
      transfer was 28.5+/-5.5 weeks. Patients were referred from hospitals with a self
      designated nursery level I (n = 115), II (n = 111), III (n = 45), or none (n =
      2). In 42 patients, (15%) no maternal or fetal indication for hospital transfer
      was identified after evaluation at the tertiary center. The most common referring
      misdiagnoses were preterm labor (n = 25), PPROM (n = 10) and preeclampsia (n =
      3). One hundred and sixty-five patients delivered during transfer admission (mean
      GA = 29.6+/-4.8 weeks); 79 infants (48%) required admission to a level III, and
      52 (31%) to a level II nursery. Most patients require the services of a tertiary
      facility after maternal fetal transfer. If delivered during transfer admission,
      the majority of neonates require care in an intermediate or intensive care
      nursery.

PMID- 9926877
TI  - Echocardiographic evidence of aortopulmonary collaterals in premature infants
      after closure of ductus arteriosus.
AB  - Aortopulmonary collaterals occur in a variety of congenital heart diseases, in
      chronic pulmonary infection and abscesses, in association with lung tumors, and
      after multiple pulmonary emboli. In patients with congenital cyanotic heart
      disease aortopulmonary collaterals mainly occur in conditions with reduced
      pulmonary blood flow. We investigated 12 preterm low-birth-weight infants,
      gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from
      moderate to severe chronic lung disease after a period of mechanical ventilation.
      All patients developed aortopulmonary collaterals after closure of a patent
      ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color
      Doppler echocardiography and originated mainly from the descending aorta or the
      aortic arch. Hypoxic and hypercapnic episodes favored the development of
      aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and
      respiratory function had improved. In only one patient coiling of a large col
      lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels
      potentially aggravate chronic lung disease by increasing collateral pulmonary
      blood flow and reducing lung compliance. We conclude that aortopulmonary
      collaterals occur in bronchopulmonary dysplasia and can cause major problems in
      ventilated premature infants. Echocardiographic evaluation is important to
      prevent aggravation of chronic lung disease of infants at risk.

PMID- 9926879
TI  - Are maternal diabetes and preeclampsia independent simulators of fetal
      erythropoietin production?
AB  - To determine if diabetes and preeclampsia are independent stimulators of
      erythropoietin, distinct from hypoxia, we measured umbilical cord plasma
      erythropoietin in 239 deliveries from 24 to 40 weeks of gestation. Mean plasma
      erythropoietin levels were not different between normal, diabetic, and
      preeclamptic women when all deliveries were analyzed. When infants with suspected
      intrauterine hypoxia were excluded, the mean erythropoietin level was
      considerably lower within all three groups but there was no difference among the
      groups. In suspected hypoxia, the mean fetal erythropoietin was elevated, but
      there was no difference between control, diabetic, or preeclamptic pregnancies.
      These results provide further support that hypoxia remains the only known
      stimulator of erythropoietin production in the fetus.

PMID- 9926878
TI  - Meter-dosed, inhaled beclomethasone attenuates bronchoalveolar oxyradical
      inflammation in premature infants at risk for bronchopulmonary dysplasia.
AB  - The object of this study was to examine the hypothesis that meter-dosed, inhaled
      beclomethasone administered to premature infants beginning at birth in a tapering
      dosage schedule over the first 12 days of life attenuates bronchoalveolar lining
      fluid oxyradical inflammation concomitant with modulation of bronchopulmonary
      dysplasia. The design of this study was an unblinded, uncontrolled phase I, pilot
      investigation of inhaled beclomethasone primarily examining safety and
      administration. The setting was a tertiary care neonatal intensive care unit.
      Intubated, premature infants were studied longitudinally to 36 weeks corrected
      gestational age. Meter-dosed, inhaled beclomethasone was administered in a
      tapering dosage schedule over the first 12 days of life. Endotracheal tube
      aspirates were collected on Days 2, 4, and 6 of life and assayed for various
      markers of bronchoalveolar lining fluid oxyradical stress. Infants were also
      assessed with regards to a number of relevant clinical variables and presence or
      absence of bronchopulmonary dysplasia at 36 weeks corrected gestational age.
      Although no differences in clinical outcome were apparent in comparing nine
      control infants with nine beclomethasone-treated infants, bronchoalveolar lining
      fluid from control infants exhibited evidence of apparent phospholipid
      peroxidation (enhanced polyunsaturated fatty acid consumption) on Day 2 of life
      compared to beclomethasone-treated infants. Significant differences were noted
      for percent arachidonic acid, total polyunsaturated fatty acids and ratio of
      polyunsaturated fatty acids, to saturated fatty acids. The ratio of monohydroxyl
      linolenic acid to native linoleic acid (a more specific marker of lipid
      peroxidation) as well as myeloperoxidase activity (a marker of neutrophil
      oxyradical stress) tended to be higher in the control group but did not achieve
      statistical significance for this small subject number study. No adverse
      reactions related to meter-dosed, inhaled beclomethasone were noted in the
      treatment group; most specifically no evidence of hypothalamic-pituitary-adrenal
      axis suppression was noted in either control or beclomethasone-treated infants.
      Meter-dosed, inhaled beclomethasone in the dosage schedule utilized was safe and
      appeared to moderate bronchoalveolar lining fluid phospholipid peroxidation.
      Small numbers of infants entered into the present investigation preclude comments
      on clinical efficacy because of the likelihood of a statistical type 2 error.
      However, additional investigations of inhaled beclomethasone initiated at birth
      in premature infants at risk for bronchopulmonary dysplasia, enrolling larger
      number of subjects and perhaps a higher dosage of beclomethasone, are warranted.

PMID- 9926880
TI  - Prenatal sonographic findings associated with malignant astrocytoma following
      normal early third-trimester ultrasonography.
AB  - We present an unusual case in which sonographic assessment at 33 weeks'
      gestation, 5 weeks following a normal fetal anatomical survey and biometry,
      demonstrated a large, irregular-shaped, echogenic, suprasellar midline
      intracranial mass occupying the anterior and middle fossas. Associated severe
      obstructive hydrocephalus with "dangling" choroid plexus bilaterally was noted
      with a markedly thin cortical mantle and increased cranial biometry. Elective
      cesarean delivery was performed due to the associated craniomegaly at 37 weeks'
      gestation. Although breathing spontaneously at delivery, the infant subsequently
      required mechanical ventilation and developed neonatal seizures. A
      ventriculoperitoneal shunt was placed on Day 3 of life. Transcranial needle
      biopsy demonstrated malignant astrocytoma (glioblastoma multiforme). This case
      suggests the rapid development of an intracranial malignant astrocytoma over a
      relatively short period of time. The significant ultrasonographic finding of an
      intracranial, destructive fetal deformation, following a normal examination 5
      weeks previously, demonstrates the limitations of screening ultrasonography in
      predicting perinatal outcome.

PMID- 9926881
TI  - Pathological evidence of prolonged umbilical cord encirclement as a cause of
      fetal death.
AB  - A case is presented in which autopsy findings (deep groove around the fetal waist
      and buttock), and gross and microscopic umbilical cord and placental examination
      (linear ulcer of umbilical cord histologically rimmed by fetal epidermal implants
      with evidence of remote bleeding) established the diagnosis of umbilical cord
      encirclement as a cause of intrauterine fetal death despite the lack of prenatal
      or postnatal obstetrical evidence.

PMID- 9926882
TI  - A randomized clinical trial of two surgical techniques for cesarean section.
AB  - The Joel-Cohen incision followed by nonclosure of pelvic and parietal peritoneum
      has been advocated as an alternative method to the Pfannenstiel incision with
      peritonealization at cesarean section. A randomized trial was designed to compare
      intra- and postoperative morbidity between the two techniques. Women to undergo a
      cesarean section were randomly allocated to have either the Joel-Cohen incision
      with the parietal and pelvic peritoneum left open (group 1) or to have the
      Pfannenstiel incision with both peritoneal layers sutured (group 2). The
      myometrium was closed with 1-0 polyglactin 910 suture using a continuous single
      layer nonlocking technique. Patients in group 2 had the peritoneum approximated
      with 2-0 polyglactin 910 suture. The fascia was sutured with continuous 1-0
      polyglactin 910 suture in all cases. Opening time was defined as the interval
      from skin incision to the opening of the uterine cavity. Febrile morbidity was
      defined as a temperature > or =38 degrees C on two occasions 4 hours (hr) apart
      excluding the first postoperative day. Endometritis was defined as postpartum
      temperature > or =38 degrees C on two occasions 4 hr apart, with uterine
      tenderness and/or foul-smelling lochia. One hundred forty-nine and 150 patients
      were allocated to group 1 and to group 2, respectively. A shorter median (range)
      opening time [4 min (2-21) vs. 6 min (2-19), respectively, p < 0.01] and a
      shorter median (range) operative time [30 min (10-65) vs. 40 min (20-110),
      respectively, p < 0.01] were observed in group 1. No difference was found in
      terms of intraoperative complications, proportion of patients who required
      transfusion, endometritis, sepsis, febrile morbidity, and urinary tract
      infections. A higher rate of wound infections was found in group 2 than in group
      1 [14 of 150 (9.3%) vs. 2 of 149 (1.3%), respectively, p < 0.01]. The Joel-Cohen
      incision without peritonealization resulted in a shorter opening and total
      operative time than the Pfannenstiel laparotomy with peritonealization. This was
      accomplished with a reduction of wound infections.

PMID- 9926883
TI  - A histological and immunohistochemical study of neuropeptide containing somatic
      nerves in the levator ani muscle of women with genitourinary prolapse.
AB  - BACKGROUND: To evaluate the changes occurring in the somatic innervation
      throughout the levator ani muscle in women with genitourinary prolapse and stress
      urinary incontinence (SUI). METHODS: Thirty-four patients with genital prolapse
      entered the study and ten subjects with non-malignant pathologies acted as a
      control group. All patients were evaluated by urodynamic investigation and an
      electromyographic study of pelvic floor muscles to define the type of urinary
      incontinence. Biopsy samples were obtained from both groups of patients: the site
      of muscle biopsies were left and right part of perirectal pubococcygeus muscle.
      The evaluation of immunoreactivity was semiquantitative and based on staining
      intensity and distribution. RESULTS: In all cases, S-100 protein and NSE
      immunoreactivities were found in nerve fascicles running throughout the striated
      muscle. NPY and VIP positivities were more intense and diffuse, whereas SP
      immunoreactivity was quite scanty. The different patterns of NPY and VIP
      expression changed in relation to degree of genital prolapse and to the presence
      of SUI. CONCLUSIONS: Our immunohistochemical study shows the presence in the
      pelvic floor of neurons that are able to synthesize neuropeptides. The lower
      immunoreactivity score of same neuropeptides (VIP, NPY) observed among patients
      with third degree genital prolapse and with SUI could be related to biochemical
      damage of the neurons with subsequent lower production of chemical messengers.

PMID- 9926884
TI  - The diagnosis of molar pregnancy by sonography and gross morphology.
AB  - BACKGROUND: In modern times molar pregnancies are often terminated before
      classical symptoms have developed. Sonography may not be conclusive and gross
      macroscopy may not reveal vesicles. If the aborted material is not sent for
      microscopy adequate follow-up of these patients will not be performed. The
      objective of this study was to evaluate the percentage of molar cases that
      potentially will be missed in a setting where material is submitted for
      histopathology only when sonography and/or gross macroscopy suggest complete- or
      partial hydatidiform mole. METHODS: Charts from 135 patients with complete
      hydatidiform mole (75) and partial hydatidiform mole (60) between 1989 1997 were
      evaluated. RESULTS: In complete hydatidiform mole sonography had been performed
      in 68 patients. The correct diagnosis had been suspected in 84% of the cases with
      the aid of sonography and/or gross macroscopy. In partial hydatidiform mole the
      correct diagnosis was suspected in only 30% of the cases. Three patients with
      complete mole developed persistent disease despite negative sonography and/or
      gross macroscopy. One patient with partial mole that was only documented by
      microscopy also developed sequelae. CONCLUSION: In a setting where material from
      curettages in early pathological pregnancies are not routinely sent for
      histopathology 16% and 70% of complete- and partial hydatidiform moles
      respectively will be missed. Since a subset of these 'discrete' moles will
      eventually require chemotherapy, this policy could have serious consequences.

PMID- 9926885
TI  - Fetal loss rate after second trimester amniocentesis at different gestational
      age.
AB  - BACKGROUND: Recent studies have debated the safety of early amniocentesis, one of
      which reported a significant increase in spontaneous fetal losses following
      amniocentesis performed at 10-13 weeks of gestation. The aim of this study was to
      determine the fetal loss rate following amniocentesis performed at different
      stages in the second trimester. METHODS: One thousand six hundred and fifty-one
      consecutive amniocenteses undertaken in a low risk population between 13 weeks+0
      days and 20 weeks+6 days were evaluated. In 87% of the women the reason for
      testing was maternal age (mean 37.1 years). Data concerning patients, procedure
      details and pregnancy outcome were recorded. RESULTS: Spontaneous abortion before
      28 weeks of gestation occurred in 1.1%, one third of which were within two weeks
      and the remaining within seven weeks after the procedure. The fetal loss rate was
      higher when the amniocentesis was performed earlier in pregnancy, at 13 weeks+0
      days exceeding 3%. Abnormal color of the amniotic fluid and leakage of amniotic
      fluid were strong predictors of fetal loss. Transplacental needle insertion did
      not increase the risk of pregnancy loss. CONCLUSION: Amniocentesis performed very
      early in the second trimester is followed by an increased fetal loss rate that
      cannot be explained solely by a higher risk of spontaneous abortion at this time
      of gestation.

PMID- 9926886
TI  - Electronic fetal monitoring: what's reassuring?
AB  - BACKGROUND: To determine which combinations of fetal heart rate pattern
      abnormalities are associated with normal outcome in term pregnancies. METHODS: A
      cohort of 2200 consecutive deliveries was examined and the fetal heart rate
      tracings analyzed. Singleton, term patients without chorioamnionitis or serious
      malformations were used to perform logistic regression analysis to select those
      FHR patterns associated with increased risk for Apgar<7 and cord pH<7.15, or
      immediate adverse outcome. RESULTS: Patients having no fetal heart rate
      abnormalities, mild variable decelerations, decreased variability, mild
      bradycardia, or accelerations present, constituted 84% of all fetal heart rate
      tracings. These tracings alone, or in combination, predicted 5 minute Apgar
      score> or =7 in 99.7%, cord pH> or =7.15 in 96.9% and no adverse neonatal
      sequelae in 96.2% of cases. Accelerations were reassuring regardless of FHR
      pattern. When these patterns were not present, non-reassuring tracings, the risk
      for immediate adverse outcome increased 50%. The non-reassuring tracings were
      both without accelerations and had tachycardia, prolonged bradycardia, severe
      variable or late decelerations, or a combination of these patterns. This
      increased risk was independent of the risk of confounders: i.e. thick meconium
      (1.8-fold), prolonged second stage of labor (>50 min., 1.5-fold), maternal
      disease (e.g. kidney, respiratory, 3-fold), or hypertensive disease (1.9-fold).
      CONCLUSIONS: The great majority of fetal heart rate pattern abnormalities can be
      considered reassuring as they are within normal variations of a healthy fetus.
      The non-reassuring ones identify infants that truly require further evaluation by
      fetal scalp, vibroacoustic stimulation, or fetal scalp blood sampling.

PMID- 9926887
TI  - Prenatal care and counseling of female drug-abusers: effects on drug abuse and
      perinatal outcome.
AB  - BACKGROUND: To evaluate the efficacy of a specific counseling and withdrawal
      program for drug-abusing pregnant women and its effect on perinatal outcome.
      DESIGN AND SETTING: An analysis of 120 pregnancies followed in 111 drug-abusing
      women giving birth at the Department of Obstetrics and Gynecology, Helsinki
      University Central Hospital, in 1985-95. METHODS: Personnel responsible for local
      maternity care in the Helsinki area were trained to identify pregnant drug
      abusers and to refer them to our hospital for clinical antenatal care and
      counseling with psychological and social support. Substance abuse during
      pregnancy was monitored by self-report and serial urine screenings. Obstetric and
      perinatal outcome were compared between those who succeeded in quitting totally
      or reducing drug use, and those who continued their drug use throughout
      pregnancy. The significance of the differences was tested by Student's unpaired t
      test and binomial t-test. RESULTS: Of the women, 62% registered before the 20th
      week of pregnancy and 32% during the 20th-29th week of pregnancy (mean 18.4+/-6.6
      weeks). Twelve women were admitted to an obstetric ward for withdrawal. In 73 of
      the 120 (61%) pregnancies the woman succeeded either in quitting totally or
      reducing drug abuse. Among this group, incidence of preterm birth (4.1%) was
      smaller (p<0.001), and gestational age (39.8+/-2.2 weeks) and birth weight
      (3393+/-605 gr) higher (p<0.05) than those (19.6%, 38.3+/-3.4 wk and 3049+/-728
      gr, respectively) in the group continuing their drug abuse. Additionally, the
      percentage of normal delivery (80.8%) was higher (p<0.05), and incidence of
      withdrawal symptoms (19.2%), lower (p<0.001) than for those who continued drug
      abuse (65.2% and 47.8%, respectively). CONCLUSIONS: Carefully monitored
      counseling program for pregnant drug abusers is effective in reducing the amount
      of drugs used and improves perinatal outcome.

PMID- 9926888
TI  - Practice variation of test procedures reportedly used in routine antenatal care
      in The Netherlands.
AB  - BACKGROUND: Pregnant women are encouraged to book for antenatal care. However,
      little is known about the contents of antenatal care, in particular regarding
      various test procedures. The present descriptive study was conducted to assess
      the variation in standard test procedures in antenatal care in The Netherlands.
      METHODS: A nationwide structured survey by mailed questionnaire was carried out
      among specialist obstetricians and midwives in The Netherlands. Representatives
      of each obstetric practice registered with the Dutch Society of Obstetrics and
      Gynecology (n=132) and a sample of midwives registered with the Dutch Society of
      Midwives (n=394) were invited to report the standard policy of tests routinely
      used for antenatal care in their own setting. Furthermore, they were asked to
      report their views on the potential impact of the antenatal care program on
      pregnancy outcome. RESULTS: Complete information was available from 105
      specialist obstetricians (80%) and 281 midwives (71%). The assessment of maternal
      blood pressure and weight are reportedly the commonest procedures routinely
      conducted during the antenatal period. However, within each profession reported
      definitions and implications of abnormal findings vary markedly, especially in
      the fields of identification and management of hypertensive disorders in
      pregnancy. Serial examination of the cervix is not standard policy among both
      groups. With respect to laboratory tests, considerable intra- and
      interprofessional variations are reported, in particular those for maternal serum
      glucose, rubella antibody titer and urinary dipstick for glucose and protein. As
      to standard ultrasound policies, wide intra- and interprofessional variations are
      noted. Seventy-two specialist obstetricians (68%) and 92 midwives (33%) routinely
      estimate the duration of gestation by ultrasound in pregnant women (p<0.001). A
      fetal anomaly scan at about 18-20 weeks' gestation is routinely offered to
      pregnant women by 31 specialist obstetricians (30%) and 44 midwives (16%)
      (p<0.01); 29 obstetricians (28%) and 11 midwives (4%) reportedly use ultrasound
      in all pregnant women for the detection of fetal growth restriction (p<0.001).
      Overall, midwives have a more optimistic view about the impact of antenatal care
      on pregnancy outcome than obstetricians. CONCLUSIONS: Although the standard
      package of antenatal care provided by both specialist obstetricians and midwives
      in The Netherlands seems to be relatively uniform, wide intra- and
      interprofessional variations exist with respect to (1) the application of tests
      in terms of recommendations to test some or all pregnant women, (2) defining
      normal from abnormal and (3) potential implications of abnormal findings.

PMID- 9926889
TI  - Manual removal of the placenta. Incidence and clinical significance.
AB  - OBJECTIVE: To determine the incidence and complications related to manual removal
      of the placenta. METHODS: Review of hospital medical records from 1990 throughout
      1994. One thousand five hundred and two vaginal deliveries from 1984 1992 were
      used for comparisons. RESULTS: A total of 24,750 deliveries were registered
      during the five year study period. Placenta was removed manually in 165 women
      (0.6%). The use of general anesthesia for manual removal of placenta decreased
      from 74% in 1990 to 19% in 1994. Spinal analgesia was applied from 1993, and it
      was used in 42% of the women in 1994. Of 74 parous women, 12 (16%) had
      experienced retained placenta before. The average difference in the hemoglobin
      concentration between the prenatal and the postoperative values was 3.4 g/dl
      among the patients, and 10% required blood transfusion (1-4 units). Among the
      controls, there was no decrease in the average hemoglobin concentration, and only
      0.5 needed blood transfusion. Endometritis following manual removal was detected
      in 1.8% of the patients and 1.5% among the controls. Despite manual removal, five
      women (3%) were considered to have retained placental fragments two days or later
      after delivery, which required curettage. CONCLUSIONS: Placenta needed to be
      removed manually in 0.60% of all deliveries in our department. It was associated
      with increased incidence of hemorrhage and consequently low hemoglobin values.
      Women with a history of retained placenta have an increased risk of recurrence of
      retained placenta in subsequent deliveries.

PMID- 9926890
TI  - The Misgav Ladach method for cesarean section compared to the Pfannenstiel
      method.
AB  - OBJECTIVE: The aim of the study was to evaluate the outcome of two different
      methods of cesarean section (CS). DESIGN: The study was designed as a
      prospective, randomized, controlled trial. SETTING: All CS were performed at the
      University Hospital in Uppsala, Sweden. POPULATION: Fifty women admitted to
      hospital for a first elective CS were consecutively included in the study. They
      were randomly allocated to two groups. METHODS: One group was operated on by the
      Misgav Ladach method for CS and the other group by the Pfannenstiel method. All
      operations were performed by the same surgeon. MAIN OUTCOME MEASURES: Duration of
      operation, amount of bleeding, analgesics required, scar appearance and length of
      hospitalization. RESULTS: Operating time was significantly different between the
      two methods, with an average of 12.5 minutes with the Misgav Ladach method and 26
      minutes with the Pfannenstiel method (p<0.001). The amount of blood loss differed
      significantly, with 448 ml and 608 ml respectively (p=0.017). Significantly less
      analgesic injections and tablets (p=0.004) were needed after the Misgav Ladach
      method. CONCLUSION: The Misgav Ladach method of CS has advantages over the
      Pfannenstiel method by being significantly quicker to perform, with a reduced
      amount of bleeding and diminished postoperative pain. The women were satisfied
      with the appearance of their scars. In this study no negative effects of the new
      operation technique were discovered.

PMID- 9926891
TI  - Gender differences in psychological reactions to infertility among couples
      seeking IVF- and ICSI-treatment.
AB  - BACKGROUND: Gender differences and similarities in psychological reactions
      related to infertility, perception of social support, the effect of infertility
      on the marital relationship and coping-style were investigated among Swedish
      couples seeking in vitro fertilization -- or intracytoplasmic sperm injection -
      treatment. METHODS: Ninety-one couples entering treatment completed the
      Infertility Reaction Scale, a self-report questionnaire with structured and open
      ended questions and the Miller Behavioral Style Scale. RESULTS: The women reacted
      more strongly to their infertility than the men as measured by the Infertility
      Reaction Scale (p<0.05). Factor analysis of the Infertility Reaction Scale
      produced three factors for men and women respectively. The first factor that
      emerged for the men was 'The male role and social pressure' and the second factor
      was 'The major focus of life'. For the women the two first factors were reversed
      compared to those of the men. The third factor 'Effect on sexual life' was
      similar for men and women. Significantly more men than women had not confided in
      anyone about their infertility problem (p<0.001). The information-seeking coping
      style was significantly correlated with infertility distress only among men
      (p<O.05). CONCLUSION: The women reacted more strongly to their infertility than
      the men and they felt an intense desire to have a child. They received more
      social support than their partners, who experienced the fulfillment of the male
      role as well as the social role to become a parent as the most central aspects of
      infertility. The information-seeking coping style was significantly correlated
      with infertility distress only among men.

PMID- 9926892
TI  - Long-term sequential treatment with combined estradiol valerate and cyproterone
      acetate in early postmenopause.
AB  - BACKGROUND: We sought to evaluate the long-term safety and efficacy of cyclic
      combined estradiol valerate and cyproterone acetate. METHODS: A six-year, single
      center, open study was performed of forty-eight recently postmenopausal women. We
      evaluated biochemical markers of bone turnover, bone mineral content, bone
      mineral density, serum lipids, climacteric symptoms, and bleeding throughout the
      six-year period. Ultrasound evaluation of the endometrium was performed yearly
      for the first two years. RESULTS: Markers of bone turnover were decreased over
      the study period, while bone mineral content and density remained unchanged. High
      density lipoprotein cholesterol levels were increased with unchanged blood
      pressure over the six years. Menopausal symptoms showed significant improvements
      within 6 months. Endometrial scan results never required hysteroscopic
      evaluation. CONCLUSION: Sequentially combined estradiol valerate and cyproterone
      acetate can be used for an indefinite number of years in women with recent
      natural menopause. Cyproterone acetate provides adequate endometrial protection
      and cycle control while allowing estradiol valerate to exert its positive effects
      on lipid profile, bone metabolism, and climacteric symptoms.

PMID- 9926893
TI  - Laser conization of cervical intraepithelial neoplasia grade 3: free resection
      margins indicative of lesion-free survival.
AB  - BACKGROUND: Various grades of cervical intraepithelial neoplasia may occur
      following laser conization for grade 3 lesions. The aim of this study was to
      assess lesion-free survival after laser conization in cases with/without free
      resection margins, and to test whether detection of human papillomavirus
      infection and/or p53 expression in the cone lesion were useful predictors of
      lesion-free survival. METHODS: In 598 women treated for cervical intraepithelial
      neoplasia grade 3 the state of the resection margins was recorded and related to
      the findings on follow-up, up to 15 years post-operatively. Lesion-free survival
      times were analyzed by the Kaplan-Meier method. The presence/absence of human
      papillomavirus infection and/or p53 expression in the primary lesion was
      investigated in every fifth case by in situ hybridization and
      immunohistochemistry respectively. RESULTS: Lesion-free survival was
      significantly more common after complete than incomplete excision of cervical
      intraepithelial neoplasia. In the latter, lesions tended to appear shortly after
      surgery, indicating the presence of residual disease. The few lesions appearing
      later were evenly divided between those with and those without complete excision.
      The results of the human papillomavirus and p53 investigations added no further
      information. CONCLUSIONS: The presence of cervical intraepithelial neoplasia in
      the cone margin gives strong indication of potential treatment failure. In its
      absence laser conization is highly effective in the treatment of cervical
      intraepithelial neoplasia, and has the advantage of providing a specimen suitable
      for the necessary histological investigation.

PMID- 9926894
TI  - Serum soluble ICAM-1 levels in the patients with cervical cancer.
AB  - BACKGROUND: We hypothesize that serum levels of the soluble intercellular
      adhesion molecule-1 (s-ICAM-1) in patients with cervical cancer are significantly
      higher than that in healthy donors and this is examined in vivo, and in vitro.
      METHODS: We measured the serum levels of the s-ICAM-1 in patients with cervical
      cancer. Furthermore, in vitro, we examined the relationship between the
      expression of ICAM-1 on the cell surface of cultured cervical cancer cells and
      the s-ICAM-1 levels in the spent media. RESULTS: The mean+/-s.d. in the patients
      with cervical cancer 884.4+/-332.4 ng/ml were significantly (all, p<0.001) higher
      than those of normal controls (mean 364.6+/-134.8 ng/ml) and in patients with
      benign disease (536.3+/-204.8 ng/ml). Interferon-gamma (IFN-gamma) treated cells
      expressed more ICAM-1 on cell surfaces than did the non-treated cells, and s-ICAM
      1 shed in the spent media from IFN-gamma treated cells were much higher than
      those of non-treated cells. CONCLUSIONS: These results indicate that the reason
      for increase of s-ICAM-1 in the patients with cervical cancer were both
      expression and shedding of ICAM-1 from cervical cancer cells especially
      influenced by cytokines, for example, IFN-gamma from surrounding lymphocytes.

PMID- 9926895
TI  - Follow-up after repair of vaginal vault prolapse with abdominal colposacropexy.
AB  - BACKGROUND: Vaginal vault prolapse after hysterectomy is a rare complication,
      with a prevalence of less than 1/2%. The vaginal depth an axis can be restored by
      colposacropexy with preservation of coital function. The aim of this follow-up
      study was to assess the results of colposacropexy with special attention to
      recurrence of prolapse and urogenital symptoms. METHODS: During a 4-year period
      35 patients with vault prolapse were operated by colposacropexy. At follow-up the
      patients were interviewed about bladder, bowel and sexual symptoms. A pelvic
      examination and measurement of residual urine was done. Perioperative
      complications and any interim surgery was recorded. RESULTS: The patients were
      multioperated, because of prolapse or incontinence prior to colposacropexy. No
      serious perioperative complications were seen, except one case of severe bleeding
      from the presacral veins. Subjectively, 82% were cured of prolapse symptoms, one
      had recurrent vault prolapse and was reoperated, four had rectocele. Five
      patients developed urge incontinence, while urge incontinence, frequency,
      nocturia and voiding problems were cured in 75%, 80%, 50% and 100%, respectively.
      One patient developed fecal incontinence. No patients had coital problems due to
      the colposacropexy. Three patients were reoperated because of intestinal
      obstruction. CONCLUSION: Colposacropexy has a cure rate of vault prolapse of 97%
      (85 100%) and a positive effect on irritative bladder symptoms.

PMID- 9926896
TI  - Rhabdomyolysis secondary to hyperemesis gravidarum.

PMID- 9926897
TI  - Third trimester intra uterine death following spontaneous hemoperitoneum.

PMID- 9926898
TI  - A perspective on the calcium antagonists in blacks (CAB) trial.

PMID- 9926899
TI  - Dietary folate intake in US adults: findings from the third National Health and
      Nutrition Examination Survey.
AB  - To estimate the dietary intake of folate in the US population, we used data from
      the first phase of the third National Health and Nutrition Examination Survey
      (NHANES III) conducted from 1988 through 1991. Using data from a single 24-hour
      dietary recall, the mean intake for the population aged 17 years and older was
      283.4 microg/day (standard error [SE] 3.8). After correcting for a single 24-hour
      dietary recall, 70.0% (SE 1.1%) met the current recommended dietary allowance
      (RDA) for folate. Because data on intake of nutritional supplements were not
      available, it is likely that a higher proportion of the United States population
      met the RDA for folate. Folate intake was not uniform in the population: men had
      higher intakes than women, and African Americans had lower intakes than persons
      of other races. African-American men had lower absolute folate intakes than white
      men (P=0.001) or Mexican-American men (P=0.002). African-American women had the
      lowest folate intakes among women (P<0.001 for white women, P=0.006 for Mexican
      American women, and P=0.003 for other women). When folate intakes were expressed
      as mg per 1,000 calories, the results were very similar. Because of methodologic
      differences in administering the 24-hour dietary recalls in NHANES II and NHANES
      III, it is unclear whether increases in dietary folate consumption have occurred
      since NHANES II, which was conducted during 1976-80, and the Continuing Survey of
      Food Intake by Individuals, which was conducted during 1985-86. The low dietary
      consumption of folate by African Americans, if confirmed, suggests the need for
      public health strategies to increase consumption of folate among this group.

PMID- 9926900
TI  - Effects of exercise training on aerobic fitness in African-American females.
AB  - Physical inactivity, a primary risk factor for cardiovascular disease, is more
      prevalent within the African-American population. Unfortunately, only a few
      investigators have documented the effects of exercise training studies on
      cardiovascular fitness in this cohort. Therefore, the purpose of this study was
      to examine the effects of a six-week endurance exercise training program on
      aerobic fitness (VO2peak) in African-American females. Twenty-five women (16
      treatment, 9 controls, mean age 23.1+/-3.9) participated in the study. The six
      week exercise training protocol consisted of exercising three times a week on a
      cycle ergometer between 60-70% VO2peak for 20 minutes. No significant changes in
      aerobic fitness were observed in the control group. However, the relative and
      absolute VO2peak significantly increased by 18% and 19%, respectively, in the
      treatment group, 21.7+/-2.6 to 25.6+/-2.8 mL x kg(-1) x min(-1) (P<.01) and
      1.77+/-2.7 to 2.11+/-3.8 L x min(-1) (P<.01). The maximal heart rates and
      respiratory exchange ratios were not significantly different between pre- and
      post-training, suggesting that similar efforts were given. These results document
      the fact that significant increases in aerobic fitness are possible with a
      moderate exercise training regime in an African-American female population.

PMID- 9926901
TI  - Renin and hemodynamic responses to exercise in borderline hypertensives.
AB  - OBJECTIVE: In this study, we examined the relationship between baseline plasma
      renin (REN) and hemodynamic variables during recovery from aerobic exercise in 10
      Caucasian (C) and 10 African-American (AA) borderline hypertensive females.
      METHODS: Subjects attended three preliminary sessions and an experimental session
      in which treadmill walking was performed for 40 minutes at a moderate intensity.
      During this session, blood was drawn at baseline prior to exercise and
      immediately following. Blood pressure and other hemodynamic variables were
      recorded at rest before exercise and for 2 hours afterwards. The average
      difference from baseline during the two hour recovery period was calculated for
      each variable and used as the dependent variable in a multiple regression
      analysis. RESULTS: For mean arterial pressure and cardiac output, the regression
      slopes did not differ between AA and C. However, during recovery, the average
      difference from baseline for systemic vascular resistance (SVR) increased in AA
      but decreased in C. CONCLUSION: In conclusion, REN had a significant effect on
      SVR but no effect on the other hemodynamic variables during recovery from aerobic
      exercise. It appears as if the peripheral vasculature in AA may be more sensitive
      than in C to the vasoconstrictive effects of the renin angiotensin system.

PMID- 9926902
TI  - Gender differences in cardiovascular risk factors in obese, nondiabetic first
      degree relatives of African Americans with type 2 diabetes mellitus.
AB  - African-American females with type 2 diabetes mellitus are at greater risk for
      cardiovascular morbidity and mortality when compared to diabetic African-American
      males and whites. To explain the gender differences in morbidity and mortality
      secondary to cardiovascular diseases (CVD) associated with type 2 diabetes
      mellitus (DM) in middle-aged, African Americans (AA), we have postulated that
      increased incidence of CVD in AA females could be ascribed in part to greater
      clustering of pre-existing CVD risks when compared to their AA male counterparts.
      We have therefore investigated the metabolic and anthropometric risk factors for
      CVD in an AA population who are genetically at greater risk for type 2 DM. We
      studied 84 healthy first-degree relatives of AA patients with type 2 diabetes, 42
      males and 42 females with a mean age 42.5+/-8.4 years, age range 25-65 years,
      matched for age and waist-to-hip circumference ratio (WHR) in order to determine
      the impact of body fat distribution pattern on CVD risks. A standard oral glucose
      tolerance test (OGTT) and an insulin-modified frequently sampled intravenous
      glucose tolerance (FSIGT) test were performed for each subject. In addition,
      lipid and lipoprotein levels, anthropometric parameters, blood pressure,
      sociodemographics and physical activity levels were obtained for each subject.
      Insulin sensitivity index (Si) and glucose-dependent glucose disposal (Sg) were
      determined using Bergman's Minimal Model method. Hepatic insulin extraction (HIE)
      was calculated as the molar ratio of basal and postprandial c-peptide and insulin
      concentrations. Mean age, annual income and percent participation in physical
      activity did not differ between genders. Despite the identical WHR, body mass
      index (BMI) (34.8+/-7.5 vs 30.3+/-6.7 kg/m2, P=0.005), and % body fat (43.8+/-7.3
      vs 28.1+/-7.7%, P=0.001) were greater in females than males, respectively. The
      systolic blood pressure(SBP), but not the diastolic blood pressure (DBP), was
      significantly lower in our female vs male group. Mean fasting and 2-hour
      postprandial serum glucose and insulin levels were significantly greater in the
      female group. In contrast, the corresponding serum c-peptide levels were not
      significantly different between the groups. Thus, the basal and postprandial
      hepatic insulin extractions (HIE) were 30% lower in the females than in the
      males. The mean absolute levels of cholesterol (C), low density lipoprotein-C
      (LDL-C), very low-density lipoprotein-C (VLDL-C), high-density lipoprotein-C (HDL
      C), and triglycerides were not significantly different between the genders. Mean
      Si was significantly lower in the females when compared to males (Si, 1.62+/-1.66
      vs 2.45+/-1.81 x 10(-4) x min(-1) (microU/ml)(-1), P=0.03). The mean Sg was
      identical in both groups (2.66+/-1.99 vs 2.67+/-1.35 x 10(-2) x min(-1), P=0.97).
      We found no significant correlations between Si and SBP and DBP, WHR, or lipids
      and lipoproteins in the females. In contrast, Si correlated significantly with
      WHR (R=-0.346, P=0.05), HDL-C (R=0.310, P=0.05), but not with BP, LDL-C, and
      triglyceride levels in the males. We conclude that nondiabetic African-American
      females manifest several metabolic and anthropometric risk factors for
      cardiovascular diseases that precede the disease by decades. Therefore, obese AA
      females with family history of type 2 DM should be particularly targeted for
      diabetes and CVD risk prevention programs using effective and practical weight
      reduction modalities.

PMID- 9926903
TI  - Can behavioral risk factors explain the difference in body mass index between
      African-American and European-American women?
AB  - African-American women are heavier than European-American women; the reasons are
      unknown. The purpose of this study was to examine potentially modifiable reasons
      for the weight difference among 86,326 female nurses. The determinants of body
      mass index (BMI) were modelled using the method of linear regression. The
      findings included the following: mean BMI (kg/m2) was 9.0% (95% CI, 7.8-10.1%)
      higher among African American (27.3) than among European-American women (25.1)
      (P<0.0001). However, recalled BMI at age 18 was equal in the two groups (21.4,
      P=0.98). Multivariate determinants of BMI include age, age 18 BMI, alcohol and
      calorie intake, exercise, marital status, parity, race, recent intentional weight
      loss, smoking, and television watching. Even after controlling for these factors,
      African-American women still had an 8.6% (95% CI, 7.7-9.5%) higher BMI than
      European-American women. Correction for error in measurement of physical activity
      attenuated this difference to 6.4% (95% CI, 5.0-7.8%). In conclusion, in this
      single occupation group, African-American women had a significantly higher BMI
      than European-American women. Age and measured behavioral factors did not explain
      this difference. However, imprecision in the measurement of diet and activity may
      explain this difference in part. Better measurement may help quantify the
      differences that are as yet unexplained.

PMID- 9926904
TI  - Birth weight of US biracial (black-white) infants: regional differences.
AB  - OBJECTIVE: The study examined the prevalence of low birth weight among biracial
      infants of black and white parents, by region of the United States. METHODS:
      Using the national linked live birth-death infant file for 1991, low birth weight
      (<2,500 g) was examined among 50,980 biracial singleton infants according to
      parental race (black mother-white father vs. white mother-black father). RESULTS:
      Nationally, the rate of low birth weight was 31% higher in the black mother-white
      father group (8.4%) than in the white mother-black father group (6.4%). The
      difference was smaller in the Northeast, reflecting a high rate (9.8%) for
      biracial infants of Puerto-Rican white mothers. The difference in the West was
      larger (75%), due to both a high rate in the black mother-white father group
      (9.1%) and a low rate for the white mother-black father group (5.2%), and
      persisted after controlling for parental education and a variety of maternal risk
      factors. CONCLUSIONS: Further studies are needed to identify the maternal factors
      involved in the regional differences in the prevalence of low birth weight among
      biracial infants.

PMID- 9926905
TI  - Outcome of recruitment and report on participation rate in the New Mexico Elder
      Health Survey.
AB  - The purpose of this paper is to report on the outcome of recruitment and
      participation rate in the New Mexico Elder Health Survey. This survey is the
      first community based epidemiological survey to examine health and health related
      issues of elderly (65 years or older) Hispanics and non-Hispanic whites in
      Bernalillo County (Albuquerque), New Mexico. This survey was conducted from May
      1993 to September 1995. Subjects (N=2200) were randomly selected from the list of
      50,700 Medicare recipients residing in Bernalillo County and stratified by
      ethnicity and gender. Hispanics were identified using a computer program that
      selects Hispanic surname patterns and ethnicity was verified by self report.
      Subjects participated in a home interview, followed by an interview and
      examination in a senior health clinic. Use of the Medicare list resulted in 75.7%
      (N=1666) of subjects being contacted. Of the 1666 subjects available, 1130
      (67.8%) completed a home interview and 883 (54%) completed the full examination.
      There were no significant differences in participation by ethnicity, but there
      were significant differences by gender, with women less likely to participate.
      The mean age of participants was 74 years, age range 65 to 100. Hispanic elderly
      demonstrated greater economic poverty and lower levels of formal education. Our
      survey results show that the elderly and Hispanic elderly can be successfully
      recruited to participate in a research study. This paper is the first to
      summarize the details of the survey design, present the results of recruitment
      and participation, and describe the survey participants.

PMID- 9926906
TI  - Patterns of atrial fibrillation at a regional hospital in Saudi Arabia.
AB  - The objective of this retrospective study was to report on the clinical
      presentation, etiology, and laboratory tests of both chronic and acute atrial
      fibrillation (AF) admitted to the cardiology unit of a teaching hospital in
      southern Saudi Arabia. We studied 219 records; 132 (60.3%) and 87 (39.7%) had
      documented chronic AF (group 1), and acute AF (group 2) respectively. The mean
      age (SD) was significantly higher in group 1 (64.6 [SD 19.4] vs 52.9 [SD 15.6])
      (P<0.001). Palpitation, dizziness and syncope were the most frequent symptoms in
      acute AF, while dyspnea was the most common presentation in the chronic type. On
      the other hand, heart failure and embolic complications were reported
      significantly in group 1, but the frequency of acute respiratory problems and
      acute myocardial infarction was similar in both groups. The most common causes of
      both types of AF were rheumatic valvular diseases (26%), IHD (24.2%),
      hypertension (23.7%), and lung diseases (13.2%); however, in 28 patients (12.8%)
      no cause was detected. The echocardiography findings of chamber dilatation, valve
      lesions, and depressed left ventricular function were significantly frequent in
      group 1 (P<0.01). Although rheumatic valvular diseases are still common in Saudi
      Arabia, ischemic heart disease and hypertension are emerging as important causes
      of AF in this developing nation, and therefore require prevention and control.

PMID- 9926907
TI  - The role of maternal hostility and family environment upon cardiovascular
      functioning among youth two years later: socioeconomic and ethnic differences.
AB  - Two hundred sixty-eight African-American and white children and their biological
      mothers participated in the study. The purpose of the study was to examine the
      potential collective impact of maternal hostile coping styles and perceptions of
      family functioning upon youths' cardiovascular (CV) functioning 2.4 years later,
      within the context of SES and ethnicity. The mother completed a set of
      questionnaires that included the Cook-Medley Hostility Scale and three scales
      from the Family Environment Scale (FES). Childrens' systolic and diastolic blood
      pressure (SBP and DBP) and impedance cardiography derived total peripheral
      resistance (TPR) was measured at rest two years later. Mothers with lower SES and
      African-American mothers reported higher levels of hostility compared to those
      with higher SES and white mothers, respectively. Lower SES mothers reported lower
      levels of family cohesion and expressiveness than higher SES mothers. Whites
      reported more family conflict and expressiveness than African Americans. African
      American and lower SES youth exhibited higher SBP and DBP values than whites and
      higher SES youth. Among lower SES African-American youth, CV functioning tended
      to be impacted negatively when their mothers rated themselves high in hostility.
      Findings suggest that ethnicity and SES may have independent as well as
      interactive impacts on the influence of maternal coping styles on the CV
      functioning of their children, particularly those from lower SES backgrounds.

PMID- 9926908
TI  - Misconceptions and mammography use among Filipino-and Korean-American women.
AB  - Face-to-face interviews were conducted with a convenience sample of 218 Filipino
      and 229 Korean women residing in Los Angeles County. This paper describes the
      women's knowledge and misconceptions regarding breast cancer risk factors, their
      utilization of traditional and westernized preventive health care, and the
      relationship of these variables to mammography utilization. Sixty-six percent of
      Filipino women and 49% of Korean women ever had a mammogram. Both Filipino- and
      Korean-American women share many of the same misconceptions about breast cancer
      risk factors. More instructive, however, is that these beliefs do not affect
      mammography utilization. Acculturation and modesty were associated with
      mammography utilization in both groups. Use of traditional medicine was
      negatively related and use of westernized preventive health care was positively
      related to mammography screening only among Filipino women. Practicing health
      care professionals should use these findings as they develop culturally sensitive
      breast cancer control programs.

PMID- 9926909
TI  - Knowledge about smoking, reasons for smoking, and reasons for wishing to quit in
      inner-city African Americans.
AB  - OBJECTIVE: To determine knowledge about smoking, reasons for smoking, and reasons
      for wishing to quit and the association of these variables with abstinence at ten
      weeks and six months. DESIGN: Descriptive study and longitudinal intervention.
      SETTING: Inner-city public hospital clinics. PARTICIPANTS: 410 African-American
      cigarette smokers interested in quitting were surveyed at baseline and
      subsequently enrolled into a double-blind, placebo-controlled, randomized trial
      of the transdermal nicotine patch. MAIN OUTCOME MEASURES: Descriptive information
      about smoking knowledge, reasons for smoking, and reasons for wishing to quit,
      and association of these variables with abstinence at 10 weeks and 6 months.
      RESULTS: Among the 410 patients randomized, mean age was 48 years, 61% were
      female, 41% had less than a high school education, 51% had an annual household
      income less than $8,000, and the average number of cigarettes smoked a day was
      twenty. The average number of questions answered correctly was nine out of eleven
      (84%). The most cited reason for smoking was relaxation/tension reduction and the
      least cited were stimulation and handling of the cigarette. Ninety-nine percent
      of patients stated they wished to quit for health reasons. Knowledge, reasons for
      smoking, and reasons for wishing to quit were not significantly associated with
      10-week or 6-month abstinence. CONCLUSIONS: In this group of inner-city African
      American smokers, knowledge about cigarette smoking was high. Reasons for smoking
      were related to relaxation, craving, and pleasure, and reasons for wishing to
      quit were largely health-related. Knowledge, reasons for smoking, and reasons for
      wishing to quit were not associated with 10 week or 6 month abstinence. Since
      knowledge about smoking is already high, future efforts should be directed at
      promoting cessation through proven behavioral and pharmacological approaches,
      rather than didactic patient education.

PMID- 9926910
TI  - The prevalence of hypertension and the status of cardiovascular health in South
      Africa.
AB  - The population of South Africa is nearly 40 million and is growing at the rate of
      2.5% per year. The population is 76.2% black, 13.3% white, 8.6% "mixed," and 2.6%
      Asian. The life expectancy (between 1985 and 1990) for whites was 69 years for
      males and 77 years for females; and for blacks, life expectancy was 61 years for
      males and 67 years for females. The major causes of death in blacks was
      accidents, poisoning and violence, which accounted for 14%. HIV/AIDS has reached
      epidemic proportions, and it is estimated that by the first decade of the next
      century between 18% and 27% of South African black adults will be infected.
      Diseases of the circulatory system claimed the most lives among whites (38.4%),
      Asians (34.1%), and the mixed group (21.8%). Coronary heart disease (CHD) was the
      major cause of death among whites and Asians in the circulatory system disease
      category and the main contributor to all causes of death. The CHD death rates of
      165.3 and 101.2 per 100,000 population for whites and Asians, respectively,
      surpassed that of the "mixed" group (55.1 per 100,000); blacks had the lowest
      rate (5.3 per 100,000). Cerebrovascular disease is first among the "mixed" group,
      followed by whites and Asians, and then blacks (73.6, 62.5, and 36.5 per 100,000,
      respectively).

PMID- 9926911
TI  - The prevalence of hypertension and the state of cardiovascular health in
      Venezuela and surrounding nations.
AB  - This review summarizes the prevalence of hypertension and the state of
      cardiovascular health in Venezuela and surrounding nations. First, the review
      discusses the fact that cardiovascular disease (CVD) is the main cause of death
      in Venezuela, Colombia, Brazil, and Trinidad and Tobago, accounting for 20% to
      35% of all deaths. These data are similar to data from the developed world.
      Second, prevalence of hypertension in this region varies from 8% to 40% in the
      adult population, and, on average, 22% of the adult population of this region has
      an elevated blood pressure. However, prevalence rates vary considerably from
      country to country and within regions of the same country. Although mortality
      from hypertension as the main cause of death accounts for 1% to 4% of all deaths,
      mortality from stroke, mainly caused by hypertension, accounts for 10% of all
      deaths, indicating a failure in the treatment of hypertension. In most Latin
      American countries, the degree of awareness, treatment and control of
      hypertension is low, necessitating the establishment of programs to prevent,
      detect and effectively treat hypertension and decrease CVD risk factors.

PMID- 9926912
TI  - Status of health and prevalence of hypertension in Brazil.
AB  - In the last 40 years Brazil has experienced both a demographic and an
      epidemiological transition. Life expectancy has increased and fertility rates
      have declined. Cardiovascular disease (CVD) has become the leading cause of
      death, as infectious disease incidence declined. Hypertension is the leading
      reason for disability benefits and a key factor for cardiovascular disease
      morbidity and mortality. Hypertension prevalence in Brazil ranges from 5% to 40%,
      depending on the region of the country and the population subgroup. Risk factors
      for hypertension are older age, higher body mass index, black ethnicity, high
      salt and alcohol intake, acculturation of native populations, and additionally,
      for women, oral contraceptive use. Although there are nationally issued
      guidelines for hypertension treatment, outcome studies evaluating such programs
      are scarce. Information available from selected populations suggest that
      hypertension awareness, treatment and control rates are very low. There is a need
      for development and implementation of primary prevention programs with adequate
      evaluation mechanisms to reduce the burden of the disease in the years to come.

PMID- 9926913
TI  - Gender and ethnic differences in some risk behaviors in high school students in
      the United States.

PMID- 9926914
TI  - Endothelial receptor tyrosine kinases activate the STAT signaling pathway: mutant
      Tie-2 causing venous malformations signals a distinct STAT activation response.
AB  - Endothelial receptor tyrosine kinases (RTKs) and their signaling mechanisms are
      of interest because they may control tumor angiogenesis and thereby tumor growth.
      In this report we have examined activation of the signal transducers and
      activators of transcription (STATs) by the three known vascular endothelial
      growth factor receptors (VEGFR1-3), as well as by the endothelial Tie-1 and -2
      receptors. We also studied signaling by the R849W mutant of Tie-2 (MTie-2), which
      has been shown to cause venous malformations. When overexpressed in 293T cells,
      MTie-2 activated STAT1 while the other endothelial RTKs failed to do so. In
      contrast, the three VEGFRs were strong activators of STAT3 and STAT5, suggesting
      that they activate only a specific subset of these signal transducers. STAT3 and
      STAT5 were also activated by Tie-2 and, more so, by MTie-2. Tyrosine
      phosphorylation and DNA binding of STATs correlated with their ability to
      activate transcription as judged by luciferase assays. When co-expressed with
      STAT5, VEGFR-1 as well as both the Tie-2 receptor forms increased expression of
      the cell cycle inhibitor p21. Interestingly, co-expression of the Tie-2 receptors
      with STAT1 resulted in appearance of a novel, p21 related transcript. Taken
      together, these findings identify STAT proteins as novel targets for signal
      transduction by the endothelial RTKs, suggesting that they may be involved in the
      regulation of endothelial function.

PMID- 9926915
TI  - The adenovirus E4orf6 protein contributes to malignant transformation by
      antagonizing E1A-induced accumulation of the tumor suppressor protein p53.
AB  - The adenovirus type 5 (Ad5) E4orf6 protein promotes focus formation of primary
      baby rat kidney (BRK) cells in cooperation with Ad5 E1 proteins. This activity is
      most likely related to the ability of the E4orf6 protein to bind to p53 and
      modulate its tumor suppressor functions. In this study we report that transformed
      BRK cells that stably express E4orf6 in addition to E1A and E1B (ABS cells)
      displayed multiple additional properties commonly associated with a high grade of
      oncogenic transformation compared to cells expressing only E1A and E1B (AB
      cells). These properties included morphological alterations, markedly enhanced
      growth rates and growth to much higher saturation densities. Following injection
      into nude mice ABS-derived tumors exhibited accelerated growth and, based on
      histopathological criteria, proofed to be much more malignant compared to tumors
      generated by AB cells. Interestingly, these highly transformed properties of ABS
      cells correlated with a dramatic reduction of p53 steady-state levels which
      inversely correlated with E4orf6 expression. From these results we conclude that
      expression of the Ad5 E4orf6 protein (i) confers additional transformed in vitro
      properties to primary rat cells expressing the Ad5 E1 proteins, and (ii)
      increases the tumorigenic and malignant potential of these cells in vivo. Our
      data suggest that the Ad5 E4orf6 protein enhances the intrinsic ability of E1
      transformed rat cells to grow in a neoplastic state by completely inactivating
      p53 tumor suppressor function in combination with the E1A and E1B proteins.

PMID- 9926916
TI  - Functional domains in cyclin D1: pRb-kinase activity is not essential for
      transformation.
AB  - Although cyclin D1 plays a major role during cell cycle progression and is
      involved in human tumourigenesis, its domain structure is still poorly
      understood. In the present study, we have generated a series of cyclin D1 N- and
      C-terminal deletion constructs. These mutants were used to define the domains
      required for transformation of rat embryonal fibroblasts (REF) in cooperation
      with activated Ha-ras and and to establish correlations with defined biochemical
      properties of cyclin D1. Protein binding and REF assays showed that the region of
      the cyclin box required for the interaction with CDK4 as well as C-terminal
      sequences determining protein stability were crucial for transformation.
      Surprisingly, however, the N-terminal deletion of 20 amino acids which impaired
      pRb kinase activity did not affect the transforming ability of cyclin D1.
      Likewise, no effect on transformation was observed with mutants defective in
      p21CIP interaction. These observations argue against a crucial role of pRb
      inactivation or p21CIP squelching in cyclin D1-mediated transformation.

PMID- 9926917
TI  - Multiplex PCR/LDR for detection of K-ras mutations in primary colon tumors.
AB  - Point mutations in codons 12, 13, and 61 of the K-ras gene occur early in the
      development of colorectal cancer and are preserved throughout the course of tumor
      progression. These mutations can serve as biomarkers for shed or circulating
      tumor cells and may be useful for diagnosis of early, curable tumors and for
      staging of advanced cancers. We have developed a multiplex polymerase chain
      reaction/ligase detection reaction (PCR/LDR) method which identifies all 19
      possible single-base mutations in K-ras codons 12, 13, and 61, with a sensitivity
      of 1 in 500 wild-type sequences. In a blinded study, 144 paraffin-embedded
      archival colon carcinomas were microdissected and K-ras mutations determined by
      both dideoxy-sequencing and multiplex PCR/LDR. Results were concordant for 134
      samples. The ten discordant samples were re-evaluated using higher sensitivity
      uniplex PCR/LDR, and the original multiplex PCR/LDR result was confirmed in nine
      of these ten cases. Multiplex PCR/LDR was able to identify mutations in solid
      tumors or paraffin-embedded tissues containing a majority of wild-type stromal
      cells, with or without microdissection. The technique is well suited for large
      scale studies and for analysis of clinical samples containing a minority
      population of mutated cells.

PMID- 9926918
TI  - Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental
      animals.
AB  - JCV is a papovavirus which is widespread in the human population. The prototype
      Mad-1 variant of JCV induces a fatal demyelinating disease of the central nervous
      system (CNS) called Progressive Multifocal Leukoencephalopathy (PML) in
      immunosuppressed individuals. The unique tropism of JCV (Mad-1) to the CNS is
      attributed to the tissue-specific regulation of the viral early promoter which is
      responsible for the production of the viral regulatory protein, T-antigen. The
      archetype form of this virus, JCV(CY), which has been repeatedly isolated from
      the urine of PML and non-PML individuals, is distinct from JCV(Mad-1) in the
      structural organization of the regulatory sequence. To characterize the tissue
      specific expression of JCV(CY) and to investigate its potential in inducing
      disease, transgenic mice containing the early region of JCV(CY) were generated.
      Some of these mice between 9-13 months of age exhibited signs of illness as
      manifested by paralysis of rear limbs, hunched posture, and poor grooming.
      Neuropathological examination indicated no sign of hypomyelination of the brain,
      but surprisingly, revealed the presence of primitive tumors originating from the
      cerebellum and the surrounding brain stem. The tumor masses also infiltrated the
      surrounding tissue. Results from RNA and protein studies revealed a high level of
      T-antigen mRNA expression in hindbrains of clinically normal and affected
      transgenic mice. However, higher levels of T-antigen RNA and protein were
      detected in brains of the animals exhibiting severe illness. The close
      resemblance of JCV(CY) induced tumor in transgenic mice to the human
      medulloblastoma/primitive neuroectodermal tumor (PNETs) in location, histologic
      appearance, and expression of marker proteins strongly suggests the utility of
      this novel animal model for the study of human brain tumors.

PMID- 9926919
TI  - A balance of signaling by Rho family small GTPases RhoA, Rac1 and Cdc42
      coordinates cytoskeletal morphology but not cell survival.
AB  - Rho family GTPases are known to be involved in cytoskeletal reorganization. We
      examined the possibility that these functions may be dictated by a balance of Rho
      family GTPase signaling. Using transient viral expression of RhoA, Rac1, Cdc42
      and their mutants, as well as C3 exoenzyme, we altered cytoskeletal organization
      under normal growth conditions. Overexpression of wild-type or constitutively
      active forms of the Rho family GTPases led to their respective activation
      phenotypes. Overexpression of dominant negative forms of given Rho family GTPases
      led to a phenotype consistent with activation of the other Rho family GTPase.
      Treatment with C. difficile toxin A, that inactivates all Rho family GTPases, led
      to the transient appearance of a variety of activation phenotypes. Previously, we
      reported that inactivation of Rho led to induction of apoptosis, implying that
      Rho may play an important role in cell survival signaling. This signaling,
      however, is not affected by expression of any forms of Rac1 or Cdc42, and only
      inactivation of Rho led to induction of apoptosis. Rho family GTPases appear to
      coordinate cytoskeletal organization by a balance of signaling, while cell
      survival is regulated by a distinct Rho-mediated signaling pathway.

PMID- 9926920
TI  - Cyclin D1 overexpression combined with N-nitrosomethylbenzylamine increases
      dysplasia and cellular proliferation in murine esophageal squamous epithelium.
AB  - We previously described the oral-esophageal tissue-specific expression of cyclin
      D1 with the Epstein-Barr virus ED-L2 promoter in transgenic mice, and resulting
      dysplasia. Given the evidence for an interplay between environmental and genetic
      factors in esophageal squamous carcinogenesis, the aim of this study was to
      determine the potential cooperation of the nitrosamine compound N
      nitrosomethylbenzylamine (NMBA), an esophageal specific carcinogen, in the cyclin
      D1 transgenic mice. NMBA was first demonstrated to induce dysplasia in two
      strains of inbred mice, C57BL/6 and FVB/N. Subcutaneous NMBA was then
      administrated to wild type and transgenic mice beginning at 4 weeks of age. Mice
      were monitored for the duration of the study for general appearance, activity and
      weight, and were euthanized at 12 and 15 months. Histopathologic analysis
      revealed increased severity of dysplasia in cyclin D1 mice treated with NMBA
      compared with treated age-matched wild-type mice and untreated mice. There was
      also increased proliferating cell nuclear antigen (PCNA) expression in the
      esophagi of NMBA treated cyclin D1 mice. Taken together, these findings suggest
      that a genetic alteration, specifically cyclin D1 overexpression and a chemical
      carinogen, NMBA, may cooperate to increase the severity of esophageal squamous
      dysplasia, a prominent precursor to carcinoma.

PMID- 9926921
TI  - Expression of the focal adhesion protein paxillin in lung cancer and its relation
      to cell motility.
AB  - Lung cancer can lead to abnormalities of the actin cytoskeleton structure which
      may be important in transformation. In this study, we have investigated the
      expression of the cytoskeletal associated protein paxillin in lung cancer.
      Paxillin is a 68 kDa focal adhesion protein, with four tandem LIM domains at the
      C-terminus, involved in growth factor receptor, integrin and oncogenic signaling
      such as v-src, BCR/ABL, and E6 of the papilloma virus. In non-small cell lung
      cancer (NSCLC) cell lines, paxillin localized to the focal adhesions. The
      possible role of paxillin in lung cancer cells was assessed by overexpressing
      green fluorescence protein (GFP)-paxillin construct in two separate NSCLC cell
      lines (Calu-1 and H661). Over the course of 48 h, GFP-paxillin consistently
      caused the cells to become round and to decrease cell motility as compared to
      normal controls, GFP-N-terminus paxillin, or GFP-LIM transfected cells. Because
      some lung cancers may be quite aggressive and metastasize quickly, which may be
      related to the cytoskeleton, we determined the expression of paxillin in NSCLC
      and small cell lung cancer (SCLC) cell lines and patient tumor tissues.
      Expression of paxillin in NSCLC and SCLC cell lines were determined by Northern
      blot and Western blot analysis. The expression of paxillin was consistently low
      in SCLC cell lines, whereas there was paxillin expression in NSCLC cell lines.
      There was a variability of expression of paxillin in NSCLC tumor tissue as
      compared to normal lung tissue. In contrast, by immunohistochemistry, we show
      that there was no detectable expression of paxillin in 5/5 SCLC patients. This
      data suggests that absence or low level of paxillin protein expression may cause
      certain lung cancers, such as SCLC, to be more motile and possibly more
      aggressive.

PMID- 9926922
TI  - Aberrant FHIT mRNA transcripts are present in malignant and normal
      haematopoiesis, but absence of FHIT protein is restricted to leukaemia.
AB  - Aberrant FHIT mRNA transcripts are present in malignant and normal
      haematopoiesis, but absence of FHIT protein is restricted to leukaemia
      Alterations of the recently cloned fragile histidine triad (FHIT) gene at
      chromosome 3p14.2 are frequent in a variety of solid tumours and cancer cell
      lines. Based on these findings, FHIT has been proposed as a putative tumour
      suppressor gene. We evaluated the mRNA expression of the FHIT gene in samples
      from 55 patients with various haematological malignancies (21 AML, 8 CML, 10 CLL,
      seven low-grade and nine high-grade Non-Hodgkin's lymphomas), in a panel of 16
      leukaemia cell lines, in normal mature haematopoietic cells of both myeloid and
      lymphoid lineage, as well as in CD34+ haematopoietic progenitor cells. Aberrant
      FHIT mRNA transcripts were observed in 14/16 (88%) leukaemia cell lines, 43/55
      (78%) primary haematological neoplasms, but also in 17/22 (77%) normal controls.
      1/16 (6%) cell lines and 7/55 (13%) neoplasms did not express any FHIT mRNA. cDNA
      sequencing revealed exonic deletions, small DNA insertions and combinations of
      both. Analysis of genomic DNA showed gene deletions in two myeloid leukaemia cell
      lines. In contrast to all normal types of haematopoietic cells, FHIT protein was
      clearly reduced or absent in 8/18 (44%) neoplastic samples tested. Our data
      indicate that whilst aberrant FHIT mRNA transcripts are seen both in normal and
      malignant cells, lack of FHIT protein is restricted to leukaemia. Absent FHIT
      protein expression might contribute to leukaemogenesis.

PMID- 9926923
TI  - Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic
      ras.
AB  - Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic
      ras Constitutive activation of the ras proto-oncogene is a frequent and early
      event in colon cancers, but the downstream nuclear targets are not fully
      understood. The Cdx-1 and Cdx-2 homeobox genes play crucial roles in intestinal
      cell proliferation and differentiation. In addition, Cdx-2 is a colonic tumour
      suppressor gene, whereas Cdx-1 has oncogenic potential. Here, we show that
      constitutive activation of ras alters Cdx-1 and Cdx-2 expression in human colonic
      Caco-2 and HT-29 cells that harbour a normal ras proto-oncogene. Oncogenic ras
      downregulates Cdx-2 through activation of the PKC pathway and a decline in
      activity of the Cdx-2 promoter AP-1 site. This decline results from a PKC
      dependent decrease in the relative expression of c-Jun, an activator of Cdx-2
      transcription, compared to c-Fos, an inhibitor of Cdx-2. Unlike Cdx-2, Cdx-1 is
      upregulated by oncogenic ras and this effect is mediated by activation of the
      MEK1 pathway. These results indicate that oncogenic ras activation has opposite
      effects on Cdx-1 and Cdx-2 expression through distinct signalling pathways and
      they provide the first evidence for a functional link between ras activation and
      the downregulation of the Cdx-2 tumour-suppressor gene in colon cancer cells.

PMID- 9926924
TI  - Mutations in the promoter reveal a cause for the reduced expression of the human
      manganese superoxide dismutase gene in cancer cells.
AB  - Manganese superoxide dismutase (MnSOD) has been shown to play an important role
      in preventing the development of cancer. MnSOD activity is reduced in many
      transformed cells and tumor tissues. We previously showed that the reduced level
      of MnSOD activity in cancer cells was not due to a defect in the primary
      structure of MnSOD protein, but rather was due to defects in gene expression. To
      elucidate the cause for the reduced expression of human MnSOD in cancer, we
      investigated the nucleotide sequence in the regulatory region of the MnSOD gene
      in a normal human cell line and various human tumor cell lines. A DNA fragment
      spanning 3.4 kb 5' flanking region of the MnSOD gene isolated from a normal human
      genomic DNA library was used to determine the DNA sequence of MnSOD promoter. PCR
      primers were used for amplification of the 3.4 kb 5' flanking region of the human
      MnSOD gene in cancer cells. Sequence analysis identified three heterozygous
      mutations in the proximal region of the promoter in five human tumor cell lines.
      These mutations, clustered around the GC-rich region of the human MnSOD promoter,
      change the binding pattern of AP-2 and lead to a reduction in transcription
      activity using a luciferase reporter assay system. These results suggest that the
      reduced level of MnSOD expression in some tumor cells is, at least in part, due
      to a defect in the DNA sequence of the promoter region.

PMID- 9926925
TI  - Comparative effects of overexpression of p27Kip1 and p21Cip1/Waf1 on growth and
      differentiation in human colon carcinoma cells.
AB  - Recent studies have shown that decreased expression of p27Kip1 is associated with
      high grade tumors and an unfavorable prognosis in several types of human cancer.
      To clarify the role of p27Kip1 in colon cancer, we have overexpressed this
      protein in the HT29 colon cancer cell line. The derivatives displayed an increase
      in the p27Kip1 protein in cyclin E/CDK2 immunoprecipitates and a decrease in
      cyclin E-associated kinase activity when compared to vector control clones,
      providing evidence that the overexpressed protein was functional. Clones with a
      high level of p27Kip1 displayed partial growth inhibition in monolayer culture
      and a decrease in plating efficiency, even though they expressed increased levels
      of the cyclin D1 protein. Using alkaline phosphatase expression as a marker, we
      found that the p27Kip1 overexpressor clones displayed a 2-3-fold increase in
      sensitivity to induction of differentiation by 2 mM sodium butyrate. In contrast
      to these results, derivatives of HT29 cells that stably overexpressed
      p21Cip1/Waf1 displayed decreased sensitivity to the induction of differentiation.
      These findings may explain why decreased levels of p27Kip1 in certain human
      cancers is associated with high grade (poorly differentiated) tumors, and suggest
      that strategies that increase the level of p27Kip1 may be useful in cancer
      therapy.

PMID- 9926926
TI  - The polyadenylation inhibitor cordycepin (3'dA) causes a decline in c-MYC mRNA
      levels without affecting c-MYC protein levels.
AB  - Study of the distribution of the poly(A) tail length of c-myc mRNA in several
      cell lines revealed a distinct, prevailing population with short poly(A) tails,
      derived through sequential deadenylation. To elucidate the possible in vivo
      function of this distinct short tailed c-myc mRNA population, the polyadenylation
      inhibitor cordycepin was used. This resulted in a decline in steady state c-myc
      mRNA levels with the remaining messenger mostly oligoadenylated. However, c-MYC
      proteins did not follow the reduction of the c-myc mRNA. On the other hand, in
      cells exposed to physiological agents known to downregulate c-myc expression, the
      reduction of mRNA steady state levels, was reflected upon c-MYC protein levels.
      The dissociation between c-myc mRNA and protein levels caused by cordycepin was
      not due to the stabilization of the c-MYC proteins and was not an indiscriminate
      effect since in the presence of cordycepin, c-fos mRNA and protein levels
      concomitantly declined. Our data indicate that under these conditions, a long
      poly(A) tail is not instrumental for c-myc mRNA translation and furthermore, the
      discrepancy in the steady state of c-myc mRNA level: c-MYC protein ratio between
      control cells and cells treated with cordycepin indicates that c-myc mRNA is
      subjected to translational control.

PMID- 9926927
TI  - PA26, a novel target of the p53 tumor suppressor and member of the GADD family of
      DNA damage and growth arrest inducible genes.
AB  - Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic
      agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive
      genes is believed to play an important role in mediating such responses. In this
      study we identified a novel gene, PA26, which maps to chromosome 6q21 and encodes
      at least three transcript isoforms, of which two are differentially induced by
      genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53-dependent
      manner. A functional p53-responsive element was identified in the second intron
      of the PA26 gene, in consistance with a mechanism of transcriptional induction of
      the PA26 gene by p53. No clues to its functions were revealed by sequence
      analysis, although pronounced negative regulation by serum factors argues for a
      potential role of PA26 in growth regulation. Immunological analysis suggests that
      PA26 protein(s) is localized to the cell nucleus. Our results suggest that the
      PA26 gene is a novel p53 target gene with properties common to the GADD family of
      growth arrest and DNA damage-inducible stress-response genes, and, thus, a
      potential novel regulator of cellular growth.

PMID- 9926928
TI  - Retinoic acid inhibits transformation by preventing phosphatidylinositol 3-kinase
      dependent activation of the c-fos promoter.
AB  - Retinoic acid inhibits transformation of cells by polyoma virus middle T
      oncoprotein. Inhibition of transformation results from a retinoic acid-dependent
      failure of cells to fully express the c-fos proto-oncogene. Retinoic acid
      prevents transactivation of the c-fos promoter by disrupting signaling between
      tyrosine kinases at the plasma membrane and trans-acting factors at the c-fos
      promoter. We used complementary genetic, biochemical and molecular approaches to
      demonstrate that: (1) phosphatidylinositol 3-kinase signaling is the principle
      mechanism of polyoma virus middle T oncoprotein activation of c-fos expression;
      (2) middle T/phosphatidylinositol 3-kinase transactivation of the c-fos promoter
      and transformation of cells requires activation of both the small GTP-binding
      protein Rac and Jun N-terminal kinase; (3) retinoic acid inhibits activation of
      Jun N-terminal kinase, thereby preventing c-fos transactivation and
      transformation; and (4) middle T activation of c-fos transcription requires both
      the serum response element and the promoter proximal cyclic AMP response element.
      These studies identify a novel target through which retinoids prevent oncogenic
      transformation.

PMID- 9926930
TI  - Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two
      novel candidate regions at 9q22.3 and 9q31.
AB  - The most common genetic alteration identified in transitional cell carcinoma
      (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However,
      localization of tumor suppressor genes on 9q has been hampered by the low
      frequency of subchromosomal deletions. We have analysed 139 primary, initial low
      stage TCC of the bladder using a panel of 28 microsatellite markers spanning
      chromosome 9 at an average distance of 5 Mb, following a primer-extension
      preamplification (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or
      more loci and partial deletions were detected in 62 (45%) tumors; apparent
      monosomy 9 was detected in only five (4%) tumors. Deletions were more frequent on
      9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion,
      suggesting that alteration of genes on 9q may be an early event associated with
      superficial papillary tumors. Combined data from the cases with partial 9q
      deletions displayed four candidate regions for tumor suppressor loci, based on
      the frequency of deletion observed and tumors with unique deletions at these
      sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a
      region encompassing loci for the Gorlin syndrome and multiple self-healing
      squamous epithelioma gene. In two other tumors, the single LOH was identified at
      the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital
      muscular dystrophy genes have been located. One tumor showed unique LOH at the
      GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the
      fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two
      tumors. This region is frequently deleted in tumors and encompasses the locus for
      the hereditary hemorrhagic telangiectasia gene. These findings suggest four
      target regions on 9q within which suppressor genes for TCC may reside.

PMID- 9926929
TI  - Chimeric Wnt proteins define the amino-terminus of Wnt-1 as a transformation
      specific determinant.
AB  - Wnt-1 induces morphological transformation of C57MG mammary epithelial cells and
      accumulation of cytosolic beta-catenin whereas Wnt-5a has no effect. To identify
      regions within the 370 amino acid Wnt-1 protein required for these functions we
      tested eleven chimeric genes that contained variable amounts of Wnt-1 and Wnt-5a
      sequence. Transformation and beta-catenin regulation in C57MG cells is controlled
      by amino acids that lie within 186 residues of the amino terminus of Wnt-1. Small
      substitutions between residues 186 and 292 reduced Wnt-1 activity. Replacement of
      the carboxy terminal 79 amino acids of Wnt-1 by Wnt-5a did not affect function.
      These results were supported by transient expression assays in 293 cells wherein
      beta-catenin accumulated in the cytoplasm in response to ectopic Wnt-1
      expression. In 293 cells, a larger region of the amino-terminus of Wnt-1 was
      found to be required for beta-catenin regulation. Nonfunctional chimeras that
      contained at least 99 amino terminal Wnt-1 residues inhibited Wnt-1 stimulation
      of 293 cells. One of these chimeras inhibited both Wnt-1 and Wnt-3 activity
      suggesting that Wnt-1 and Wnt-3 interact with a common signaling component.

PMID- 9926931
TI  - Anti-tumor activity of antizyme which targets the ornithine decarboxylase (ODC)
      required for cell growth and transformation.
AB  - Anti-tumor activity of antizyme which targets the ornithine decarboxylase (ODC)
      required for cell growth and transformation Cell proliferation and transformation
      induced by growth factor stimulation or by carcinogens, viruses, or oncogenes are
      characterized by an associated increase in polyamine levels, which is mediated by
      increased polyamine biosynthesis and enhanced uptake of polyamines. Polyamine
      biosynthesis is catalyzed particularly, in the level of ornithine decarboxylase
      (ODC). The elevation of cellular polyamine levels on the other hand accelerates
      the induction of ornithine decarboxylase antizyme (antizyme), which is involved
      not only in ODC-degradation, but in the negative regulation of polyamine
      transport. Taking advantage of these characteristics of antizyme, the potential
      of antizyme as a factor having anti-cell growth and anti-tumor activity was
      investigated. We show that antizyme can induce cell death associated with a rapid
      decline of intracellular polyamine contents. The possible anti-tumor activities
      of ectopically expressed antizyme were tested in p21H-ras (Val 12)-transformed
      NIH3T3 cells and several human malignant cell lines including a line with loss of
      p53 expression, and they were shown to be as sensitive as nontransformed NIH3T3
      cells in vitro. The in vivo anti-tumor activity was also tested using nude mice
      inoculated with H-ras transformed NIH3T3 cells that had been transfected with
      inducible antizyme expression vector and the results showed that antizyme
      expression in vivo blocks tumor formation in these mice. These results suggest
      that ectopic antizyme expression is of possible therapeutic benefit in the
      treatment of cancer, which is mediated by ODC inactivation and intracellular
      polyamine depletion.

PMID- 9926933
TI  - Microsatellite instability in European hepatocellular carcinoma.
AB  - Genetic instability has been detected in many types of cancers but poorly
      investigated in hepatocellular carcinoma (HCC). We have studied the incidence of
      microsatellite instability (MI) at eight highly polymorphic microsatellite
      markers and the poly A tract BAT26 and tested for mutations at two sites of
      repetitive sequence (poly-A nucleotides 709-718 and GT repeat-nucleotides 1931
      1936) in the Transforming Growth Factor beta (TGFbeta) type II receptor (RII)
      gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This
      analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and
      41% in two or more loci. No mutations of the TGFbetaRII gene were found in the MI
      positive tumours. No correlation was found with clinicopathological
      characteristics of the tumours such as cirrhosis, etiology, number of nodules,
      Edmondson's grade and vascular invasion. However, in patients who had a
      rearranged D16S402 microsatellite in their tumour, the recurrent disease and the
      number of nodules were significantly higher than in the others (P<0.005 and
      P<0.02, respectively). We propose to consider D16S402 rearrangement in HCC as a
      prognostic factor to identify patients presenting a higher risk of recurrence.

PMID- 9926932
TI  - ASK1 mediates apoptotic cell death induced by genotoxic stress.
AB  - ASKI mediates apoptotic cell death induced by genotoxic stress Genotoxic stress
      induced apoptosis is mediated by caspase family proteases as triggered by other
      stimuli. In this study, we found that the DNA-damaging agent cisplatin (cDDP)
      activated MAP kinase kinase kinase ASK1 and subsequent downstream subgroups of
      MAP kinase kinase, SEK1 (or MKK4) and MKK3/MKK6, which in turn activated c-Jun N
      terminal kinase 1/stress-activated protein kinase (JNK1/SAPK) and p38 MAP kinase
      prior to caspase family protease activation and the onset of apoptosis in human
      ovarian carcinoma (OVCAR-3) and human kidney (293T) cells. As reported
      previously, benzyloxy carbonyl-Asp-CH2OC(O)-2, 6-dichlorobenzene (Z-Asp), a
      preferential inhibitor of caspase family proteases, blocked the apoptosis of
      OVCAR-3 cells induced by the genotoxic stress cDDP. Z-Asp, however, did not
      inhibit ASKI activation and the subsequent kinase cascades. Overexpression of
      kinase-negative ASK1 (K709R), which inhibited ASK1 activation and the downstream
      MKK3-p38 and MKK4-JNK1 pathways, also suppressed the caspase protease activation
      and apoptosis induced by cDDP. These results indicate that the ASK1 pathway is
      involved in genotoxic stress-induced apoptosis and mediates apoptosis at a step
      upstream of caspase protease activation.

PMID- 9926934
TI  - Comparative study of the p53-mdm2 and p53-MDMX interfaces.
AB  - Mdm2 and MDMX are two structurally related p53-binding proteins which show the
      highest level of sequence similarity in the N-terminal p53-binding domains. Apart
      from its ability to inhibit p53 mediated transcription, a feature it shares with
      mdm2, very little is known about the physiological functions of MDMX. It is
      clearly distinct from mdm2 since its expression appears not to be regulated by
      p53 and it cannot compensate for lack of mdm2 in early development. We present
      data on the structural similarity between the p53 binding pockets of mdm2 and
      MDMX using p53- and phage-selected peptides. From the results we conclude that
      our recently devised innovative approach to reverse the mdm2-mediated inhibition
      of p53's transactivation function in vivo would probably target MDMX as well.
      Strategies for selectively targeting mdm2 and MDMX are suggested and a possible
      mechanism for regulating the p53-mdm2/MDMX interactions by protein
      phosphorylation is discussed.

PMID- 9926935
TI  - Resistance to avian leukosis virus lymphomagenesis occurs subsequent to proviral
      c-myc integration.
AB  - Most chicken strains are highly susceptible to avian leukosis virus (ALV)
      induction of bursal lymphoma, involving proviral integration within the c-myc
      proto-oncogene, while certain strains are genetically resistant to
      lymphomagenesis. A nested PCR assay was developed to analyse the appearance of
      proviral c-myc integrations after ALV infection of lymphoma-susceptible birds,
      and to determine whether these integrations arise in lymphoma-resistant birds.
      Proviral c-myc integrations are detected in bursa and other tissues from 6 day
      old lymphoma-susceptible birds infected as embryos. The abundance of bursal cells
      carrying these integrations increases roughly 40-fold by 35 days of age,
      indicating that these cells hyperproliferate within the bursal environment.
      Bursal cells with proviral c-myc integrations also arise soon after infection of
      lymphoma-resistant embryos. However, these cells expand much more slowly than
      cells from lymphoma-susceptible birds. Both strains show the same rate of viral
      infection, so that resistance to lymphomagenesis occurs at a step subsequent to
      proviral c-myc integration. Proviral c-erbB gene integrations arise at the same
      frequency in bursa and other tissues of both strains, and they do not increase in
      abundance during development. These findings indicate that the mechanism of
      resistance to lymphomagenesis involves specific inhibition of cells with proviral
      c-myc integrations within the bursa.

PMID- 9926936
TI  - Evolutionary conservation and somatic mutation hotspot maps of p53: correlation
      with p53 protein structural and functional features.
AB  - Missense mutations in p53 frequently occur at 'hotspot' amino acids which are
      highly conserved and represent regions of structural or functional importance.
      Using the p53 mutation database and the p53 DNA sequences for 11 species, we more
      precisely defined the relationships among conservation, mutation frequency and
      protein structure. We aligned the p53 sequences codon-by-codon and determined the
      degree of substitution among them. As a whole, p53 is evolving at an average rate
      for a mammalian protein-coding gene. As expected, the DNA binding domain is
      evolving more slowly than the carboxy and amino termini. A detailed map of
      evolutionary conservation shows that within the DNA binding domain there are
      repeating peaks and valleys of higher and lower evolutionary constraint. Mutation
      hotspots were identified by comparing the observed distribution of mutations to
      the pattern expected from a random multinomial distribution. Seventy-three
      hotspots were identified; these 19% of codons account for 88% of all reported p53
      mutations. Both high evolutionary constraint and mutation hotspots are noted at
      amino acids close to the protein-DNA interface and at others more distant from
      DNA, often buried within the core of the folded protein but sometimes on its
      surface. The results indicate that targeting highly conserved regions for
      mutational and functional analysis may be efficient strategies for the study of
      cancer-related genes.

PMID- 9926937
TI  - Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis.
AB  - We targeted expression of human/fly chimeric Bcr-Abl proteins to the developing
      central nervous system (CNS) and eye imaginal disc of Drosophila melanogaster.
      Neural expression of human/fly chimeric P210 Bcr-Abl or P185 Bcr-Abl rescued abl
      mutant flies from pupal lethality, indicating that P210 and P185 Bcr-Abl can
      substitute functionally for Drosophila Abl during axonogenesis. However,
      increased levels of neurally expressed P210 or P185 Bcr-Abl but not Drosophila
      Abl produced CNS defects and lethality. Expression of P210 or P185 in the eye
      imaginal disc produced a dominant rough eye phenotype that was dependent on
      dosage of the transgene. Drosophila Enabled, previously identified as a
      suppressor of the abl mutant phenotype and substrate for Drosophila Abl kinase,
      had markedly increased phosphotyrosine levels in Bcr-Abl expressing Drosophila,
      indicating that it is a substrate for Bcr-Abl as well. Drosophila, therefore, is
      a suitable model system to identify Bcr-Abl interactions important for signal
      transduction and oncogenesis.

PMID- 9926938
TI  - Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma.
AB  - Substantial evidence implicates amplification of the N-myc gene with aggressive
      tumor growth and poor outcome in neuroblastoma. However some evidence suggests
      that this gene alone is not the sole determinant of outcome in N-myc amplified
      tumors. We have searched for genes that co-amplify with N-myc in neuroblastoma by
      means of two-dimensional analysis of genomic restriction digests. Using this
      approach, we have identified and cloned a novel genomic fragment which is co
      amplified with N-myc in neuroblastomas. This fragment was mapped in close
      vicinity to N-myc on chromosome arm 2p24. It was amplified in 5/8 N-myc amplified
      neuroblastoma cell lines and in 9/13 N-myc amplified tumors. Using a PCR-based
      approach we isolated a 4.5 kb c-DNA sequence that is partly contained in the
      genomic fragment. The open reading frame of the cDNA encodes a predicted protein
      of 1353 amino acids (aa). The homology of the predicted protein, which we
      designated NAG (neuroblastoma amplified gene), to a C. elegans protein of as yet
      unknown function, and its ubiquitous expression suggest that NAG may serve an
      essential function. By Northern blot analysis we showed that amplification of the
      cloned gene correlates with over-expression in neuroblastoma cell lines.
      Amplification and consequent over-expression of NAG may, therefore, contribute to
      the phenotype of a subset of neuroblastomas.

PMID- 9926939
TI  - Cyclin D1 associates with the TBP-associated factor TAF(II)250 to regulate Sp1
      mediated transcription.
AB  - We have previously shown that Sp1-mediated transcription is stimulated by Rb and
      repressed by cyclin D1. The stimulation of Sp1 transcriptional activity by Rb is
      conferred, in part, through a direct interaction with the TBP-associated factor
      TAF(II)250. Here we investigated the mechanism(s) through which cyclin D1
      represses Sp1. We examined the ability of cyclin D1 to regulate transcription
      mediated by Gal4-Sp1 fusion proteins, which contain the Gal4 DNA-binding domain
      and Sp1 trans-activation domain(s). The domain of Sp1 sufficient to confer
      repression by cyclin D1 was mapped to a region important for interaction with
      TAF(II)110. We further demonstrate that TAF(II)250-cyclin D1 complexes can be
      immunoprecipitated from mammalian and baculovirus-infected insect cells and that
      recombinant GST-TAF(II)250 (amino acids 1-434) associates with cyclin D1 in
      vitro. Moreover, the overexpression of Rb or CDK4 reduced the level of TAF(II)250
      cyclin D1 complex. The amino terminus of cyclin D1 (amino acids 1-100) was
      sufficient for association with TAF(II)250 and for repressing Sp1-mediated
      transcription. Taken together, the results suggest that cyclin D1 may regulate
      transcription by interacting directly or indirectly with TAF(II)250.

PMID- 9926940
TI  - Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia
      telangiectasia cells.
AB  - Cells from patients with the human genetic disorder ataxia-telangiectasia (A-T)
      are defective in the activation of cell cycle checkpoints in response to ionizing
      radiation damage. In order to understand the role of ATM in checkpoint control we
      investigated whether Schizosaccaromyces pombe chk1, a protein kinase implicated
      in controlling the G2 DNA damage checkpoint, might alter the radiosensitive
      phenotype in A-T cells. The fission yeast chkl gene was cloned into an EBV-based
      vector under the control of a metallothionein promoter and transfected into A-T
      lymphoblastoid cells. Induction of chk1 enhanced the survival of an A-T cell line
      in response to radiation exposure as determined by cell viability and reduction
      of radiation-induced chromosome aberrations. This can be accounted for at least
      in part by the restoration of the G2 checkpoint to chk1 expressing cells. There
      was no evidence that chk1 expression corrected either the G1/S checkpoint or
      radioresistant DNA synthesis in S phase in these cells. These results suggest
      that chk1 when overexpressed acts downstream from ATM to restore the G2
      checkpoint in these cells and correct the radiosensitive phenotype. These data
      allow us to dissociate individual checkpoint events and relate them to the
      radiosensitive phenotype in A-T cells.

PMID- 9926941
TI  - Differential expression of NF1 type I and type II isoforms in sporadic borderline
      and invasive epithelial ovarian tumors.
AB  - The NF1 gene, a putative tumor suppressor gene, contains a GAP related domain
      (GRD) which accelerates hydrolysis of ras-bound GTP to GDP, thereby converting
      the ras oncogene from its active to inactive form. Two forms of the NF1 GRD
      transcript (Type I and Type II) are differentially expressed in neuroectodermal
      tumor tissue relative to differentiated neural cells, and in gastric cancer cell
      lines relative to normal stomach mucosa. We measured relative expression of NF1
      Type II and Type I isoforms in cultured normal and malignant human ovarian
      surface epithelial cells(HOSE) and in invasive and borderline ovarian tumor
      tissue. We demonstrated an 11-fold increase in Type II:Type I ratio in 7 HOSE
      cultures relative to eight ovarian cancer cell lines. Our findings indicate a
      significant decrease in Type II isoform expression and increase in Type I
      expression in ovarian cancer cells and tumor tissue relative to HOSE cells. We
      also demonstrate an increase in Type II:Type I ratio, and a decrease in cell
      proliferation rate in three ovarian cancer cell lines on treatment with retinoic
      acid. We propose that differential expression of the NF1 Type I and Type II
      isoforms is related to cellular differentiation in ovarian epithelial cancer and
      strategies based on alteration in NF1 isoform expression may have therapeutic
      potential in ovarian malignancies.

PMID- 9926942
TI  - The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates
      transcription from the p21WAF1/CIP1 promoter.
AB  - Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1
      are associated with high risk for developing breast and ovarian cancers. Several
      studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and
      growth/tumor suppression. BRCA1 associates with p53 and stimulates transcription
      in both p53 dependent and p53-independent manners. BRCA1 splice variants BRCA1a
      (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. Here we show
      that BRCA1a and BRCA1b proteins stimulate p53-dependent transcription from the
      p21WAF1/CIP1 promoter. In addition, the C-terminal second BRCA1 (BRCT) domain is
      sufficient for p53 mediated transactivation of the p21 promoter. Previous studies
      emphasized the importance of the BRCT domain, which shows homology with p53
      binding protein (53BP1), in transcriptional activation, growth inhibition and
      tumor suppression. Our findings demonstrate an additional function for this
      domain in protein-protein interaction and co-activation of p53. We also found
      that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. The p53
      interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa
      1760-1863). The BRCT domain binds to the central domain of p53 which is required
      for sequence specific DNA binding. These results demonstrate for the first time
      the presence of a second p53 interaction domain in BRCA1 proteins and suggests
      that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. This
      BRCT domain also binds in vitro to CBP. These results suggest that one of the
      mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300
      associated HAT/FAT activity for acetylation of p53 to specific promoters
      resulting in transcriptional activation.

PMID- 9926943
TI  - Functional association of TGF-beta receptor II with cyclin B.
AB  - Utilizing the cytoplasmic tail of Transforming Growth Factor Receptor Type II
      (TGFbeta RII) as bait in a yeast two hybrid system, we have identified human
      cyclin B2 as a direct physical partner of TGFbeta RII. Analysis of deletion
      mutants of glutathione-S-transferase (GST)-cyclin B2 mapped its binding domain
      for TGFbeta RII to the C-terminal and revealed a negative regulatory region
      immediately upstream of the cyclin box. Using recombinant proteins, Cdc2 was
      demonstrated to indirectly interact with TGFbeta RII via cyclin B2. This
      interaction was reproduced in THP-1 monocytic cells, where TGFbeta treatment
      markedly enhanced the ability of cyclin B2 and, correspondingly, Cdc2 from
      TGFbeta-treated THP-1 cells, to bind the GST-TGFbeta RII fusion protein. More
      importantly, TGFbeta RII co-precipitated with cyclin B2 in TGFbeta-treated THP-1
      cells. TGFbeta treatment also caused threonine phosphorylation of Cdc2 in the
      TGFbeta RII-cyclin B2-Cdc2 complex in THP1 cells, in parallel with down
      regulation of Cdc2 function as measured by histone H1 kinase activity. Cyclin B1
      had the same capacity to bind TGFbeta RII and mediate indirect Cdc2 binding.
      These results suggest an alternative mechanism that cell cycle arrest in the G1/S
      phase caused by TGFbeta may, in part, be due to inactivation of cyclin B/Cdc2
      kinase, which is needed for entry into the G2/M phase.

PMID- 9926944
TI  - p16INK4 mediates contact-inhibition of growth.
AB  - Growth of non-transformed cells in vitro is regulated by density-dependent
      mechanisms via cell-cell contacts, leading to arrest in late G1-phase at
      confluency (contact-inhibition of growth). In the present study it is shown that
      this results from p16INK4-mediated dissociation of the complex cdk4-cyclin D1,
      which is responsible for the inactivation of the gate keeper of G1-S transition,
      the retinoblastoma protein pRb. As a consequence of the inactivation of cdk4,
      downstream the activation of cdk2 and hyperphosphorylation and thus inactivation
      of pRb was impaired. Direct evidence for the central role of p16INK4 in growth
      control comes from the observation that a competitive inhibitor of p16INK4
      repressed contact inhibition of growth. These findings provide an explanation for
      the high incidence of mutation or loss of INK4 in human tumours.

PMID- 9926945
TI  - Radiolucent lines: a question of nomenclature.

PMID- 9926946
TI  - The natural history of tibial radiolucent lines in a proximally cemented stemmed
      total knee arthroplasty.
AB  - A total of 207 tibial components in total knee arthroplasty (TKA) have been
      reviewed at a maximum of 10 years after replacement. Twelve knees developed
      aseptic femoral loosening and were reviewed separately from the remaining 195.
      All tibial components were fixed with cement confined to the proximal surface of
      the implant combined with an uncemented stem. In the 195 TKAs with well-fixed
      femoral components and (presumably) low wear, 15% of tibiae developed early
      onset, nonprogressive partial radiolucent lines (RLLs), typically in relation to
      preoperative sclerosis. Tibial component vertical migration was measured in 36
      components: no migration was detected over the course of 5 years whether or not
      an RLL was present. There was no case of tibial osteolysis, no tibial component
      was revised for aseptic loosening, and no implant was radiologically loose. In 12
      knees, the femoral component loosened with subsidence exposing peripheral bone
      that caused severe HDP wear. Tibial RLLs were present in 9, and osteolysis was
      present in 11 (although the tibial component was actually loose in only 1). This
      material has been used to study 1) the natural history of RLLs in cemented TKA
      and 2) the outcome of using cement confined to the proximal part of the tibial
      interface. We conclude that in low-wear prostheses RLLs are due to a failure to
      inject cement into sclerotic bone. Such lines are nonprogressive and do not
      affect fixation. In the presence of severe wear, however, they may provide a
      portal for the entry of debris into the interface causing progression of the RLL
      and lysis. Proximal cement plus an uncemented stem furnishes adequate tibial
      fixation, provided that the HDP wear rate is low.

PMID- 9926947
TI  - Hydroxyapatite coating versus cemented fixation of the tibial component in total
      knee arthroplasty: prospective randomized comparison of hydroxyapatite-coated and
      cemented tibial components with 5-year follow-up using radiostereometry.
AB  - Fifty-three consecutive patients (57 knees; mean age, 69 years) entered a
      prospective randomized study to compare the fixation of hydroxyapatite (HA)
      coated (29 knees) with cemented (28 knees) tibial components in the Tricon II
      total knee arthroplasty. The quality of the fixation during 5 years
      postoperatively was evaluated with radiostereometric analysis (RSA). Three HA
      coated implants were revised: 2 owing to infection, and 1 owing to early
      delamination of the coating and clinical loosening. Eight patients (9 knees)
      died, 1 patient sustained a stroke, and 1 patient refused investigations after 1
      year. In the 40 patients (19 HA-coated, 21 cemented) remaining at 5 years, the
      magnitude of the micromotion between the HA-coated and cemented groups did not
      differ. The HA-coated implants displayed most of the migration within the initial
      3 months then stabilized, whereas the cemented implants showed an initially
      lower, but over time continuously increasing migration. Between 1 and 2 years, 4
      of 24 HA-coated and 10 of 23 cemented implants migrated >0.2 mm and were
      categorized unstable, which has been shown to have a prognostic value as regards
      future aseptic loosening. Progressive radiolucent lines developed in 2 cemented
      knees, which both were categorized unstable. If HA-coated implants can sustain
      the forces that threaten the fixation in the early period after implantation, a
      strong and enduring fixation may be obtained.

PMID- 9926948
TI  - Total hip arthroplasty for osteonecrosis: matched-pair analysis of 188 hips with
      long-term follow-up.
AB  - A matched comparison was made between total hip arthroplasties done for
      osteonecrosis and those done for osteoarthritis. Patients were matched for age,
      sex, surgical approach, prosthesis, and surgeon. All received cemented Charnley
      replacements and had minimal follow-up of 10 years. There were 118 women and 70
      men with a mean age of 58 years. Thirty-five patients were younger than 50. The
      mean follow-up was 17.8 years (range, 10 to 25.4 years). Revision rates for
      osteonecrosis and osteoarthritis were 18% and 19% (not significant). The
      mechanical failure rate (revision for loosening plus radiographic loosening) was
      greater, but not significantly so, in the osteonecrosis group. In patients
      younger than 50 years, the revision rate in osteonecrosis (50%) was significantly
      higher than that in any other group. Similarly, the mechanical failure rate in
      osteonecrosis was significantly greater in the patients younger than 50.
      Radiographic femoral loosening was greater in osteonecrosis at all follow-up
      intervals, and dislocations occurred more frequently in the osteonecrosis group
      than in the osteoarthritis group. Results of arthroplasty in both groups were
      comparable in patients over 50 years of age, although patients with osteonecrosis
      had an increased rate of dislocation. Patients with osteonecrosis who are younger
      than 50 years have a significantly higher rate of mechanical failure than those
      with osteoarthritis who are younger than 50 years. Cemented total hip
      arthroplasty should be recommended in this group with caution if at all.

PMID- 9926949
TI  - Comparison of the midvastus muscle-splitting approach with the median
      parapatellar approach in total knee arthroplasty.
AB  - A total of 100 patients having bilateral total knee replacements simultaneously
      were randomized prospectively--one knee having a vastus muscle-splitting approach
      and the other knee having a median parapatellar approach-to evaluate differences
      in lateral release, postoperative rehabilitation, ease of approach, and
      complications in total knee replacement surgery. There were 25 lateral releases
      on the muscle-splitting side and 26 on the median parapatellar side (P = .871).
      There were no differences in range of motion on day 2 or discharge, straight-leg
      raise, terminal knee extension, extensor lag, lateral release, or rehabilitation.
      There were 2 postoperative hematomas and 1 manipulation, all on the muscle
      splitting side. All complications occurred from the muscle-splitting side. The
      muscle-splitting approach cannot be recommended as being superior to the median
      parapatellar approach.

PMID- 9926950
TI  - A comparison of the midvastus and paramedian approaches for total knee
      arthroplasty.
AB  - This prospective, double-blinded evaluation of 24 osteoarthritic patients
      undergoing bilateral total knee replacement compared the midvastus and standard
      parapatellar approaches. The midvastus approach was found to offer an early
      advantage in terms of less pain and earlier return to function. There were no
      significant complications associated with the midvastus approach. This approach
      should be a part of the knee surgeon's armamentarium.

PMID- 9926951
TI  - Revision hip surgery in the elderly: is it worthwhile?
AB  - We prospectively analyzed the outcome in 103 consecutive patients undergoing
      revision hip replacement, dividing the patients into 2 groups according to their
      age at the time of surgery. There were 45 patients aged 75 years or older and 58
      patients aged younger than 75 years. The results of revision hip replacement in
      terms of pain relief, functional improvement, and patient satisfaction did not
      differ between the 2 groups. There was a significantly higher death rate among
      the elderly patients (13.3% versus 1.7%; P = .0202) and a significantly higher
      rate of dislocation (20% versus 1.7%; P = .0019). We conclude that revision hip
      replacement is an effective operation in the elderly, but that patient and
      surgeon must be aware of the risks that such surgery entails.

PMID- 9926952
TI  - Preliminary results of partial surface replacement of the femoral head in
      osteonecrosis.
AB  - We report our initial results using a partial surface replacement for
      osteonecrosis of the femoral head. We believe the prosthesis has the most
      minimalist design that has been reported either in Europe or North America. The
      surgical technique, implant design, and instrumentation cause minor soft tissue
      disruption and require little bony resection. We report the results of our first
      25 prostheses performed over the past 5 years in 19 patients. The mean age was
      42.5 years, (range, 24-59 years), with a preoperative Ficat classification of 15
      hips, stage III; 9 hips, stage IV; and I hip, stage II. For the surviving
      prostheses, mean follow-up was 43 months, (range, 20-60 months). Of these 19
      surviving implants, 15 continue to function well with excellent or good hip
      scores according to the Merle d'Aubigne system. We have had 6 failures: 1 owing
      to technical error, 4 owing to local tissue factors, and 1 owing to a progression
      of the osteonecrosis. The parameters for the use of this prosthesis are defined
      with our increasing experience, and the prosthesis is compared with other
      prosthetic implants available. In comparison with alternative techniques, the
      operative surgery is straightforward requiring little preoperative planning;
      immediate weight bearing is allowed postoperatively. Should failure occur, little
      bone stock loss is incurred, and revision to a total hip replacement is as simple
      as primary hip arthroplasty.

PMID- 9926953
TI  - Cartilage degeneration in relation to repetitive pressure: case study of a
      unilateral hip hemiarthroplasty patient.
AB  - In vivo acetabular contact pressures were measured over 32 months in an elderly
      man with a pressure instrumented hemiarthroplasty. After death, left
      (hemiarthroplasty) and right (control) acetabula were explanted. Cartilage
      thickness and degeneration were quantified from magnetic resonance imaging and
      histological analysis. Highest repetitive in vivo contact pressures during gait
      (4.5 to 6.5 MPa) were measured in the superior dome of the acetabulum and
      decreased at a rate of approximately 1 MPa per year after implant (R2 = 0.48, P <
      .001). Contact pressure magnitudes measured during gait correlated positively
      with regional histology score (R2 = 0.34, P < .0001) and negatively with
      cartilage thickness (R2 = 0.35, P < .0001). Although histology scores were
      typical of early osteoarthritis (histological grade of 4-6), there were no
      significant differences in overall histology score for the left and right
      acetabula (P = .23). We conclude that acetabular cartilage degeneration was
      explained, in part, by repetitive stress, but the degeneration did not appear to
      be mediated solely by articulation with the metallic endoprosthesis.

PMID- 9926954
TI  - Impaction allografting of the proximal femur using a Charnley-type stem: a cement
      mantle analysis.
AB  - The preoperative and early postoperative radiographs of 50 patients undergoing
      femoral impaction grafting with a modified Charnley stem and dedicated impaction
      grafting instrumentation were assessed to determine the predictability of the
      cement mantle being produced. The minimal cement mantle thickness was >2 mm in
      76.7%, <2 mm in 12.7%, and absent in 10.7% of Gruen zones analyzed. There was no
      obvious zonal distribution to the areas of adequate or inadequate cement
      thickness. These values compare favorably with the results of other systems, and
      this may be due, in part, to a greater differential between the size of the graft
      impactors and the definitive prostheses.

PMID- 9926955
TI  - An evaluation of bone loss after total hip arthroplasty for femoral head necrosis
      after femoral neck fracture: a quantitative CT study in 16 patients.
AB  - This study was conducted to determine if bone and muscle loss is reversible in
      patients who had undergone total hip arthroplasty (THA) owing to necrosis of the
      femoral head after osteosynthesis for a displaced femoral neck fracture. The
      cortical bone mineral density (BMD), bone volume, bone mass, and muscle volume of
      the thigh and the BMD of the distal femur and proximal tibia were measured by
      quantitative computed tomography in 16 patients. Both extremities were measured
      just before reoperation. The measurements were repeated 3 and 6 months later. At
      reoperation, there was a mean 12% relative loss of bone mass and 23% loss of
      muscle volume in the middle femur on the fractured side compared with the
      uninjured side. In the distal femur and proximal tibia, there was a relative loss
      of BMD of 14% and 21% on the fractured side. Six months after reoperation, we
      found no change in bone mineral at any location on either side. The muscle of the
      thigh showed a gain in volume of 20% on the reoperated side but no change on the
      uninjured side. At the time of reoperation, we noted a marked bone and muscle
      loss on the fractured side. We failed to note any restoration of bone mineral
      after THA despite remobilization, which is expressed as an increase in muscle
      volume on the reoperated side. This study indicates that osteopenic bone has
      difficulties in adapting to patients' improved mobility after reoperation.

PMID- 9926956
TI  - Temporal changes of periprosthetic bone density in patients with a modular
      noncemented femoral prosthesis.
AB  - Bone mineral density changes surrounding a porous-coated proximal modular sleeved
      hip prosthesis were determined as a function of time over a 24-month period. The
      periprosthetic bone regions were defined by the 7 Gruen zones. Measurements were
      obtained with a dual-energy x-ray densitometer using a dedicated software
      program. Inclusion criteria required that the patients had primary implants, were
      asymptomatic with Harris hip scores of > or =95 for the duration of the study,
      and showed no radiographic evidence of loosening. The protocol specified that
      bone measurements be obtained within 1 week after surgery as a baseline reference
      and at 3, 6, 9, 12, 18, and 24 months thereafter. A total of 111 consecutive
      patients were enrolled in this ongoing prospective study, of whom 52 had 4 or
      more measurements after the initial baseline determination for statistical
      analysis. At 3 months, all zones showed a significant decrease in bone mineral
      density relative to the baseline measurements, and their mean loss ranged from
      6.5% to 11.2%. By 24 months, mineral losses relative to baseline varied from 0 to
      11% for Gruen zones 1 to 6. Relative to the 3-month levels, there was no
      significant change in zones 1, 4, and 6; a significant improvement in zones 3 and
      5; and a small but significant loss in zone 2 at 24 months. Gruen zone 7, the
      medial femoral neck cortex, differed in that it was the site of greatest bone
      mineral loss, attaining a mean of 20.2% at 24 months. It was found that the
      amount of periprosthetic mineral loss at 12 months was independent of the initial
      baseline reference bone mineral levels. Results of this study show the normal
      temporal bone mineral changes surrounding a proximally modular porouscoated
      femoral implant. The pattern of change demonstrated may be peculiar to the
      prosthesis used in this study because it might differ in implants of different
      design and material composition.

PMID- 9926957
TI  - Preoperative bone mineral density of the proximal tibia and migration of the
      tibial component after uncemented total knee arthroplasty.
AB  - Twenty-two patients with primary osteoarthrosis of the knee all operated on with
      insertion of an uncemented total knee arthroplasty had a preoperative measurement
      of bone mineral density (BMD) in the coronal plane of the proximal tibia
      performed by dual-photon absorptiometry. Postoperatively and with follow-up after
      6 weeks (n = 21), 1 year (n = 22), and 3 years (n = 19), radiographs suitable for
      radiostereometric analysis of the tibial component migration were obtained. One
      year postoperatively, stress examinations were performed with the aim of
      measuring inducible displacement of the tibial component. Most of the migration,
      expressed as maximal total point motion (MTPM), occurred during the first year
      with an average migration of approximately 1 mm. Regression analysis showed a
      positive relation between BMD and MTPM after 6 weeks (P = .03, r = .47), 1 year
      (P = .0005, r = .68), and 3 years (P = .02, r = .54). Inducible displacement did
      not reveal any significant relation to BMD. MTPM between 1 and 3 years, which is
      the clinically most important parameter with respect to later loosening of the
      tibial component, showed a negative relation to BMD (P = .04, r = -.47). Thus,
      tibial components of knees with preoperative high tibial BMD showed less
      continuous migration.

PMID- 9926958
TI  - Knee stability in meniscal bearing total knee arthroplasty.
AB  - The effect of a meniscal bearing on knee laxity in anterior cruciate ligament
      sacrificing total knee arthroplasty was evaluated in 7 cadaver knees using a knee
      testing device that measured knee flexion angle as well as laxity to medial
      lateral, anterior-posterior [AP], and rotational loads. A standard fixed tibial
      component and mobile tibial components (AP sliding, rotationally sliding, and AP
      and rotationally sliding) were used to evaluate AP, rotational, and varus-valgus
      stability and maximal flexion and extension with the neutrally positioned and
      malrotated tibial tray. The AP movable components increased AP laxity, and the
      fixed component decreased rotational laxity significantly when compared with the
      normal knees. The rotationally movable components did not change knee laxities
      significantly even when the tibial tray was malrotated. No significant difference
      among the components was detected when the maximal flexion and extension angles
      were compared in the neutrally positioned tibial tray. Malrotation of the tibial
      tray decreased the maximal extension angle in the fixed component. This study
      showed that the rotationally movable component can achieve near-normal laxity
      regardless of tibial tray rotation, but AP mobility of the bearing produces AP
      laxity that could lead to implant failure.

PMID- 9926959
TI  - The effect of bone compaction on early fixation of porous-coated implants.
AB  - The effect of a bone compaction technique versus conventional drilling on the
      early fixation of porous-coated implants was examined in a canine model.
      Compaction dilation resulted in a significant increase in implant fixation
      stiffness (P < .01) and ultimate fixation strength (P < .01) at 0 and 3 weeks.
      Fixation stiffness remained significantly increased at 6 weeks (P < .01);
      however, the ultimate fixation strength was not statistically significant between
      the 2 techniques (P > .05). There was no significant difference in either
      fixation value at 9 weeks (P > .05). Histological examination of the bone-implant
      interface demonstrated an increase in the density of cancellous bone immediately
      adjacent to the implants placed in the compaction dilated holes. The results of
      this study suggest that the compaction method of host bone preparation may
      optimize the initial stability of the implant interface of porous-coated
      prostheses.

PMID- 9926960
TI  - Cerclage wiring technique after proximal femoral fracture in total hip
      arthroplasty.
AB  - Cerclage wires have been used to stabilize proximal femoral cracks after stem
      insertion in cementless total hip arthroplasty. The objective of this study was
      to determine the optimal number and orientation of cerclage wires necessary to
      prevent stem subsidence and crack propagation. The crack was stabilized by 1, 2,
      or 3 wires placed either normal to the femoral neck axis or normal to the crack.
      The femora were compressed to 2,670 N while measuring crack opening and stem
      subsidence. Wires placed normal to the crack allowed less stem subsidence by 3.17
      mm and less crack opening by 1.55 mm compared with wires placed normal to the
      neck. The addition of multiple wires reduced subsidence by 50% and reduced crack
      opening to <1 mm. Medial and anterior calcar cracks are best stabilized by at
      least 2 cerclage wires that are placed normal to the crack.

PMID- 9926961
TI  - Predicting the position of the femoral head center.
AB  - To find an accurate method to predict the position of the normal head center in
      severely deformed hips without a contralateral reference, we studied the
      relationships between the head center and dimensions of the normal proximal femur
      using cadaveric specimens. From a large anatomic collection, 32 cadaveric femora
      with neck-shaft angles ranging from 115 to 146 were selected. The two parameters
      with the greatest correlation with the height of the femoral head were the height
      of the neck isthmus (r = .932) and the lowest point of neck saddle (r = .790).
      Medial head offset was most strongly correlated with the offset of the neck
      isthmus (r = .945) and the distance from the medullary axis to the outer borders
      of the medial cortex at the +30% level (r = .861). As a rule of thumb, the height
      of the head center can be predicted as the height of the midpoint of the neck
      isthmus plus 10 mm or as the height of the neck saddle with an accuracy of +/-5.1
      mm and +/-8.3 mm. The offset of the head center can be predicted as the offset of
      the midpoint of the neck isthmus plus 15 mm or as the distance from the medullary
      axis to the medial cortex at the +30% level plus 15 mm with an accuracy of +/-4.6
      mm and +/-6.3 mm.

PMID- 9926962
TI  - Non-Hodgkin's lymphoma as an unexpected diagnosis in a shoulder arthroplasty.
AB  - Shoulder arthroplasty (SA) is commonly performed in patients with rheumatoid
      arthritis (RA) who have been treated with long-term immunosuppressive medication.
      RA is associated with an increased risk of neoplasms of the immune system. A case
      of non-Hodgkin's lymphoma as an unexpected diagnosis after the routine pathologic
      examination of the soft tissues after SA was detected in a 54-year-old woman with
      long-standing RA and prolonged immunosuppressive therapy. Although this case does
      not support the cost-effectiveness of routine specimen evaluation during SA, we
      suggest that histological analysis of the surgical tissues is appropriate and
      should be performed in all patients who have been treated with prolonged
      immunosuppressive medication, especially RA patients as well as patients who have
      suspicious surgical findings.

PMID- 9926963
TI  - Fracture of the tibial tray after total knee arthroplasty.
AB  - We report a case in which fracture of the metal tibial plate was thought to be
      caused by a combination of neutral anatomic rotation of the femoral component and
      an undersized tibial plate. This resulted in medial subsidence and baseplate
      fracture with loosening of the polyethylene and dislocation of the prosthesis.

PMID- 9926964
TI  - Patellotibial fusion for patellar tendon rupture after total knee arthroplasty.
AB  - Patellar tendon rupture is a rare but recognized complication of total knee
      arthroplasty. Multiple repair methods have been described in the literature. This
      unique case involved a patient with an underlying metabolic disorder and poor
      soft tissue quality. A patellotibial fusion was used to achieve a more definitive
      reestablishment of the extensor mechanism and to improve the patient's level of
      activity.

PMID- 9926965
TI  - Use of Ilizarov external fixation for a periprosthetic supracondylar femur
      fracture.
AB  - Supracondylar femur fractures above a total knee replacement are rare injuries
      that may be challenging to treat. We present a case of an elderly woman whose
      supracondylar femur fracture was not deemed amenable to conventional treatment.
      This patient underwent fixation of her femur fracture above a total knee
      replacement using an Ilizarov external fixator. The fixator was removed at 10
      weeks, at which time the fracture was solidly healed. At the most recent follow
      up, the patient is 19 months postinjury. She is fully weight bearing without
      walking aids and has a knee range of motion of 0 degree to 110 degrees.

PMID- 9926966
TI  - Bisphosphonates for metastatic bone pain.

PMID- 9926967
TI  - Accommodation for patients and carers during relocation for treatment for
      leukaemia: a descriptive profile.
AB  - Patients with haematological disorders and their families must adjust to a wide
      range of psychosocial stresses, including coming to terms with a life-threatening
      diagnosis and coping with aggressive and invasive treatment regimens. The stress
      of this situation is exacerbated for many patients who must relocate to a
      metropolitan area for specialist treatment. This discussion presents research
      findings that indicate that for many of these patients the need for accommodation
      during relocation for treatment is a problem that should be given serious
      consideration. It is anticipated that this descriptive profile of a successful
      response to the problem of accommodation for leukaemia patients will provide
      useful data for the development of such services elsewhere.

PMID- 9926968
TI  - Experience with and attitudes to chemotherapy among newly employed nurses in
      oncological and surgical departments: a longitudinal study.
AB  - Based on questionnaires, attitudes to chemotherapy were compared between newly
      employed nurses in oncology departments and surgical departments. Comparisons
      were made as they started in their new jobs and after 6 and 12 months. In total,
      76 nurses were included in the study; 41 were employed in oncology departments
      and 35 in surgical departments. The questionnaires presented a hypothetical
      situation involving a toxic chemotherapy regimen. The subjects were asked to
      indicate the minimal benefit with respect to percentage chance of cure, length of
      life prolongation, and percentage symptom relief they would demand before
      accepting the toxic chemotherapy. The groups were well matched. On starting in
      their new jobs, both groups demanded identical chances of cure (23%) for the
      hypothetical treatment to be acceptable. Nurses < or =30 years demanded less
      chance of cure than those >30 years. There were no differences in wishes about
      life prolongation and symptom relief. The groups reported equivalent job
      satisfaction during the first year. At 6 months, 60% of the oncology nurses and
      11% of the surgical nurses reported altered attitudes to chemotherapy, and
      approximately 70% of these in both groups had become more positive. At 6 months
      surgical nurses demanded less chance of symptom relief than the oncology nurses
      to accept the chemotherapy regimen. Otherwise, there were no differences between
      the groups during the first year. Attitudes to chemotherapy showed no differences
      between newly employed nurses in oncology and in surgical departments, and there
      were no changes in either group during the first year in their new jobs.

PMID- 9926969
TI  - Current practices in the oral management of the patient undergoing chemotherapy
      or bone marrow transplantation.
AB  - Abstract The oral complications associated with cancer chemotherapy and bone
      marrow transplantation may be prevented or ameliorated by aggressive dental and
      oral hygiene interventions. Pretherapy dental evaluation and medically necessary
      oral care can eliminate potential sites of infection and trauma. A
      multidisciplinary approach, systematic oral assessment and consistent oral
      hygiene measures are critical and may be the most important factors in the
      prevention of significant complications.

PMID- 9926970
TI  - Pamidronate treatment in patients with malignant osteolytic bone disease and
      pain: a prospective randomized double-blind trial.
AB  - The aim of this double-blind, randomized study was to compare the effects of two
      pamidronate dosages, given as repeated infusions in patients with advanced
      malignant osteolytic bone disease and bone pain. Seventy patients were randomly
      assigned to receive pamidronate 60 mg or 90 mg i.v. every 3 weeks for a maximum
      of six cycles. Pain parameters, analgesic consumption and performance status were
      assessed at baseline and throughout the study. Furthermore, total-body bone
      mineral density was measured using dual-energy X-ray absorptiometry at baseline,
      after three and after six infusions. Sixty percent (95% CI 41-77%) of the
      patients in the 60 mg group and 63% (95% CI 44-79%) of the patients in the 90-mg
      group had a sustained reduction of pain intensity and were classified as pain
      responders. Median duration of pain response was 15 versus 12 weeks in the 60-mg
      and 90-mg groups, respectively (P = 0.32). After two infusions, significant
      changes in pain intensity, pain frequency, general well-being and WHO pain score
      were observed (P<0.01). A trend toward improved performance status and reduced
      consumption of analgesics was also observed. Patients in the 90-mg group had more
      pronounced bone remineralization as measured by total-body bone mineral density.
      No significant difference was detectable between the two pamidronate treatments
      in any of the parameters evaluated. In conclusion, bone pain can be effectively
      reduced by repeated pamidronate infusions in patients with advanced osteolytic
      bone disease. Pamidronate 90 mg every 3 weeks results in higher bone
      remineralization, but this difference did not translate into a further increase
      of palliative effects.

PMID- 9926971
TI  - Activity of quinolones against viridans group streptococci isolated from blood
      cultures of patients with haematological malignancy.
AB  - Use of fluoroquinolones for antimicrobial prophylaxis during neutropenia is often
      cited as a significant predisposing factor for viridans group streptococcus (VGS)
      bacteraemia. Newer compounds in this class are reputed to have enhanced activity
      against Gram-positive bacteria, and we determined the minimal inhibitory
      concentrations (MICs) for ciprofloxacin and three of the newer compounds:
      trovafloxacin, fleroxacin and clinafloxacin, against 44 isolates of VGS. On a
      gravimetric basis, clinafloxacin was most active (MIC90 0.19 mg/l), whereas
      ciprofloxacin and fleroxacin were the least active (both MIC90 16 mg/l).
      Clinafloxacin warrants further study as an agent of prophylaxis against bacterial
      infection in neutropenic patients.

PMID- 9926972
TI  - Assessing suspected spinal cord compression: a multidisciplinary outcomes
      analysis of 342 episodes.
AB  - The object of this work was to evaluate the assessment and document the outcomes
      of cancer patients with suspected spinal cord compression (SCC). In a
      retrospective cohort study of 342 episodes of suspected SCC in cancer patients
      evaluated by computed tomography (CT) of the spine, a multidisciplinary team of
      neurologists, radiologists, and oncologists assessed the impact of varying the
      anatomical criterion for SCC and including new SCC diagnosed shortly after
      definitive radiographical imaging. We developed a logistic regression model to
      identify independent clinical predictors of SCC, including the natural history of
      the underlying cancer as well as neurological and radiological risk factors.
      Management of suspected SCC infrequently involved neurology consultation (21% of
      episodes). The frequency of SCC increased more than four-fold when the definition
      was expanded to include epidural cancer rather than spinal cord displacement only
      (36% vs. 8%), and 90-day clinical follow-up identified few new lesions not
      evident on definitive imaging studies. Clinical information about the course of
      cancer (documentation and duration of metastatic cancer) added independent
      predictive information to that yielded by neurological assessment and prior
      imaging studies in a multiple regression model. The a priori predicted risk of
      SCC, which ranged from 4% to 87% in this study, may vary enough to affect
      treatment strategies, although our population may have excluded very-low-risk
      patients. Consistent anatomical definitions of SCC, clinical follow-up of
      definitive imaging studies and the addition of information on the natural history
      of cancer to traditional neurological and radiographical evaluation may all
      improve clinical assessment of suspected SCC in cancer patients.

PMID- 9926973
TI  - Hematogenous trichosporonosis in cancer patients: report of 12 cases including 5
      during prophylaxis with itraconazol.
AB  - Twelve cases of Trichosporon spp. fungemias occurring in a national cancer
      institution within 10 years are described. The trend of hematogenous
      trichosporonosis within the last 10 years is increasing. While no cases occurred
      in 1988-1991, after 1991, Trichosporon spp. was the most common species among non
      Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that
      started while the patients were receiving prophylaxis with oral itraconazole, and
      2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias
      were catheter associated. Risk factors for fungemia were: central venous
      catheter, broad-spectrum antibiotics (third-generation cephalosporins plus
      aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic
      chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3%
      mortality). Amphotericin B was administered to all but 1 patient, who was not
      treated because he died the day after his culture was found to be positive for T.
      beigelii, before antifungals were administered. All cases infected with T.
      pullulans were catheter related, and all these patients died. One of the
      remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus),
      and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy
      with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy.
      Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis
      with antifungals and catheter as source of fungemia, breakthrough fungemia) were
      significantly associated with Trichosporon spp. fungemia, in comparison to 63 C.
      albicans candidemia occurring in the same period at the same institution.
      Attributable mortality of hematogenous trichosporonosis was also significantly
      higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.

PMID- 9926975
TI  - When all else fails: stepwise multiple solutions for a complex cancer pain
      syndrome.
AB  - In the presence of insufficient pain relief and substantial adverse effects,
      application of alternative routes of administration and a change of opioid are
      the main methods used to improve the analgesic response. When all else fails, the
      result may further be optimized using adjuvant drugs by an alternative route,
      namely the intrathecal route. A stepwise approach with multiple drugs and routes
      of administration is described. This was implemented to resolve a complex pain
      syndrome otherwise considered uncontrollable. We found it possible to manage a
      very difficult pain situation by intrathecal home infusion through the efforts of
      a well-trained family and GP and a continuous exchange of information and advice
      with the pain relief team about changes in therapy to adapt to the clinical
      situation. A stepwise and a meaningful approach to clinical problems with use of
      advanced techniques and alternative drugs in the patient's home may be helpful in
      the treatment of conditions otherwise considered intractable.

PMID- 9926974
TI  - Oral cisapride for the control of delayed vomiting following high-dose cisplatin.
AB  - Although combination antiemetics prevent vomiting during the initial 24 h after
      high-dose (> or =100 mg/m2) cisplatin, many patients experience delayed emesis 24
      120 h afterwards despite receiving prophylactic dexamethasone and metoclopramide
      during this time. Cisapride is a prokinetic agent, which stimulates propulsive
      motility throughout the gastrointestinal tract without causing extrapyramidal
      effects. In this phase II trial, we tested the ability of cisapride to prevent
      delayed emesis following cisplatin. Twenty patients receiving initial cisplatin
      >100 mg/m2 were entered. All patients received intravenous dexamethasone with
      either metoclopramide or ondansetron to prevent acute emesis 0-24 h after
      receiving cisplatin. Patients who had experienced two or fewer acute vomiting
      episodes then received cisapride 20 mg orally four times daily for 4 days (24-120
      h after cisplatin). Cisapride prevented delayed emesis in 2 patients (10%) during
      the entire 4-day period (95% confidence interval, 1-32%). Abdominal cramping and
      pain occurred in 35%. At the dose and schedule tested, oral cisapride prevented
      delayed emesis in only 10% of patients receiving cisplatin >100 mg/m2 and caused
      abdominal cramping in 35%. Since in prior trials among similar patients, placebo
      prevented delayed emesis in 11%, further study of cisapride and dose escalation
      for this indication are not recommended.

PMID- 9926976
TI  - Must we really fear toxicity of conventional amphotericin B in oncological
      patients?
AB  - Fungal infections are an important cause of morbidity and mortality in patients
      with malignancies. Therefore, the use of amphotericin B (AmB) is essential for
      these patients. Results from the literature to date show that renal toxicity is
      the most serious adverse effect of AmB. Renal impairment manifests as a decrease
      in glomerular filtration and damage to tubular function. Currently, there is no
      reliable method of preventing nephrotoxicity. We have observed that sodium
      supplementation alone may not prevent nephrotoxicity. We noted that a large
      decrease in serum potassium and magnesium was followed by a significant reduction
      in creatinine clearance and an increase in both serum urea and creatinine.
      Therefore, we surmised that potassium and magnesium supplements corresponding to
      the amounts lost by the kidneys, as well as sufficient hydration, are necessary
      to prevent renal function damage. We decided to test our hypothesis in 32 cancer
      patients. During AmB therapy, serum electrolyte concentrations and biochemical
      parameters of renal function and fluid balance were monitored frequently. The
      daily ion supplementation corresponded to the amount lost through the kidneys.
      The total duration of administration ranged from 4 to 39 days, with a mean of
      13.7 days (median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88
      mg/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The
      daily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of
      i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesium was 9.0
      mmol. The frequency of infusion-related side-effects was only 10.0%. These
      reactions were treated with hydrocortisone. We observed a significant increase in
      potassium and magnesium lost through the kidneys, and a significant increase in
      fractional sodium and potassium excretion through the renal tubuli. We did not
      observe a significant increase in serum creatinine and ion imbalances.
      Interestingly, the average creatinine clearance did not decrease, but actually
      increased slightly, though to a statistically insignificant degree, from 1.425
      ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use.
      Sufficient hydration of patients and ion supplementation corresponding to the
      amount lost by the kidneys is an effective prophylaxis for prevention of AmB
      induced decrease in renal function and for countering imbalances of serum
      electrolyte concentrations during use of AmB. The frequency of infusion-related
      side-effects is minimal relative to other reports.

PMID- 9926977
TI  - The absence of a triphasic renovascular response by the multicalyceal kidney of
      the primate in reaction to acute, complete, unilateral, ureteric obstruction.
AB  - The early renovascular response by the ipsilateral kidney to acute, total,
      unilateral, ureteric obstruction was investigated in the adult male chacma baboon
      (Papio ursinus). Complete occlusion was effected by ligating the ureter at the
      brim of the bony pelvis ("N"=10). Sham studies were enacted using the same method
      but the ureter was not obstructed ("N"=11). Haemodynamic reactions were monitored
      for 12 hours. Compared with the sham-occluded set, the renal pelvic pressures in
      the obstructed group were significantly increased (P<0.05) from the second hour
      of the inquiry. However, there were no significant differences in renal blood
      flow, either between or within the respective cohorts. In this study, the
      renovascular response to acute ureteric occlusion was similar to that displayed
      by the multicalyceal kidney of other species under identical conditions. This
      reaction was fundamentally different to that exhibited by the unicalyceal kidney
      under similar circumstances.

PMID- 9926978
TI  - Fetal growth in the baboon during the second half of pregnancy.
AB  - The normal growth profile of critical fetal organs through the last third of
      gestation has not been documented in detail in human fetuses or the fetus of any
      nonhuman primate species. Recent epidemiological studies in human pregnancy
      suggest that fetal growth plays a major role in the programming of life-long
      health by modifying cardiovascular, pancreatic, brain, and liver growth. The
      present study aimed to produce a detailed database of individual organ growth in
      the fetal baboon in late gestation. Fetal organ weights were obtained from 43
      baboon fetuses between 121 and 177 days of gestation. Various organs (brain,
      heart, kidney, femur, intestines, and spinal cord) showed no sign of slowed
      growth in late gestation while growth of others (lung, liver, stomach, and
      bladder) accelerated in late gestation. The fetal adrenal and thymus showed a
      decrease in growth rate over the final 20 and 10 days of gestation respectively.
      These observations provide a database that will permit analysis of factors
      responsible for regulation of normal and altered fetal organ development in this
      important experimental species.

PMID- 9926979
TI  - Plasma and red blood cell total phospholipid fatty acid status of nonpregnant
      female Vervet monkeys (Cercopithecus aethiops) on a high carbohydrate maintenance
      diet.
AB  - Nonhuman primates are of interest as models of human physiology to study the
      effect of multiple pregnancies on birth weight. Reference plasma and red blood
      cell (RBC) total phospholipids fatty acids were established in nonpregnant
      breeding female Vervet monkeys. Twenty-three clinically healthy nonpregnant
      Vervet monkeys (Cercopithecus aethiops), contained in a controlled closed
      environment and consuming a high carbohydrate diet (68 E%) that contained 20 E%
      fat and 12 E% protein were sampled for blood during a cross-sectional study. A
      low intake of omega3 fatty acids was reflected by a high omega6/omega3 ratio
      (66:1) of the diet. Inverse relations were seen between plasma and RBC total
      phospholipid fatty acids, 18:2omega6, 20:3omega6, and 20:4omega6, which suggested
      selective incorporation in membranes. Low levels of 20:5omega3 and 22:6omega3 of
      plasma and RBC total phospholipids render Vervet monkeys as ideal subjects to
      study the effect of omega3 fatty acid supplementation on pregnancy outcomes.

PMID- 9926980
TI  - Histopathological studies of senile plaques and cerebral amyloidosis in
      cynomolgus monkeys.
AB  - Senile plaques (SPs) and cerebral amyloid angiopathy (CAA), pathological
      hallmarks of Alzheimer's disease, have not been thoroughly investigated
      histopathologically in nonhuman primates. To determine the onset age and
      histopathological characteristics of SPs and CAA, we examined the brains of 64
      cynomolgus monkeys (Macaca fascicularis) from 2 to 35 years old. Mature
      (classical and primitive) plaques appeared in 16 out of 25 monkeys that were >20
      years old. Moreover, mature plaques were observed more frequently than diffuse
      plaques and were located in the temporal cortex of the superior or inferior gyri
      and amygdala. Diffuse plaques in contrast to mature plaques did not show definite
      tendencies in onset age and distribution. CAA appeared in more than 22-year-old
      monkeys in 10 out of 16 animals and was frequently observed in capillaries and
      often found adjoining mature plaques. During immunohistochemical examination, an
      antiserum for amyloid beta protein (A beta) 1-40 could detect all SPs, whereas a
      monoclonal antibody for A beta 8-17 could not detect any diffuse plaques and only
      one third of the primitive plaques. As for CAA, the polyclonal antiserum was more
      sensitive than the monoclonal antibody. The present study describes the
      histopathological features of SPs and CAA in old cynomolgus monkeys.

PMID- 9926981
TI  - The origin and pattern of distribution of the posterior intercostal arteries in
      the baboon (Papio ursinus).
AB  - The posterior intercostal arteries of six female and four adult male baboons
      (Papio ursinus) were investigated by latex injection and subsequent dissection to
      determine their origin and pattern of distribution. Basic morphological and
      functional similarities with that of man could provide some base-line data
      pertinent to future experimental studies in the areas of thoracic aortic aneurysm
      and aortic atherosclerotic lesion in man. Basic similarities were observed
      between the baboon and man in the number of intersegmental arteries, the origin
      of the first two pairs of posterior intercostal arteries, and the anastomosis
      between the superior intercostal and the third posterior intercostal arteries.
      However, the baboon showed a craniocaudal sequence of paired orifices giving rise
      to paired arteries; orifices with incompletely divided septum giving rise to
      paired arteries; single orifices leading to a common trunk, which finally gives
      rise to paired arteries; and single orifices opening into single arteries. In
      addition, there was a craniocaudal decrease in the distance between any given
      pair of intercostal arteries and an increase in the spacing between adjacent
      pairs of intercostal arteries. Where a single artery supplied one side of the
      intercostal space, the contralateral side received a collateral branch, either
      from the preceding or succeeding intercostal artery. Though the basic
      organisation of the origin and distribution of the posterior intercostal arteries
      in the baboon is similar to that of man, the differences observed in the baboon
      might be attributed to factors such as body size, mode of activity, and even the
      phylogenetic level of development of the baboon.

PMID- 9926982
TI  - Telomere dynamics in HIV-1 infected and uninfected chimpanzees measured by an
      improved method based on high-resolution two-dimensional calibration of DNA
      sizes.
AB  - We developed an improved method for accurately measuring telomere lengths based
      on two-dimensional calibration of DNA sizes combined with pulsed field
      electrophoresis and quantitative analysis of high-resolution gel images. This
      method was used to quantify the length of telomeres in longitudinal samples of
      peripheral blood mononuclear cells (PBMCs) from five chimpanzees infected with
      human immunodeficiency virus type 1 (HIV-1) and three uninfected animals, 14 to
      27 years of age. The average length of the telomere restriction fragments (TRF)
      of infected and uninfected chimpanzees were 11.7 +/- 0.25 kbp, and 11.6 +/- 0.61
      kbp, respectively, and were about 1 kbp and 3 kbp longer than those of human
      infants and 30 year old adults, respectively. There was a trend of a slight
      decrease (30-60 bp per year) in the TRF of two HIV infected chimpanzees over 30
      35 months, while the TRF of one naive chimpanzee slightly increased over 20
      months. Although the number of chimpanzees in this study is small and no
      statistically significant linear dependencies on time were observed, it appears
      that in chimpanzees, rates of shortening of the TRF are comparable or smaller
      than in adult humans and are not significantly affected by HIV-1 infection, which
      may be related to the inability of HIV-1 to cause disease in these animals.

PMID- 9926983
TI  - Determination of fetal biparietal diameter without the use of ultrasound in
      squirrel monkeys.
AB  - This study evaluated manual caliper measurement of fetal BPD in Saimiri through
      the abdomen of the dam (TBPD) for correlation with paired ultrasound
      measurements, prediction of delivery date, subspecies variation, prediction of
      pregnancy outcome, and correlation between postpartum BPD and TBPD. Regression
      analysis revealed a close relationship between TBPD measurements and those
      obtained by ultrasound (P < 0.001). TBPD for Saimiri boliviensis boliviensis
      increased from a mean of 14.8 +/- 0.3 mm for 11 weeks prepartum to a delivery
      week measurement of 33.2 +/- 0.2mm. Delivery-week TBPD of Saimiri boliviensis
      peruviensis were significantly smaller than Saimiri sciureus sciureus (P < .05).
      Delivery week TBPD had a correlation coefficient of 0.64 with paired post-patrum
      measurements. No complications were associated with the technique. Delivery date
      could be predicted within two weeks. TBPD is an inexpensive, safe, rapid method
      of approximating fetal growth during the last half of pregnancy in Saimiri.

PMID- 9926984
TI  - A possible case of myiasis in a wild moustached tamarin, Saguinus mystax
      (Callitrichinae, Cebidae)

PMID- 9926985
TI  - Suprapontine control of respiration.
AB  - Despite focus on brainstem areas in central respiratory control, regions rostral
      to the medulla and pons are now recognized as being important in modulating
      respiratory outflow during various physiological states. The focus of this review
      is to highlight the role that suprapontine areas of the mammalian brain play in
      ventilatory control mechanisms. New imaging techniques have become invaluable in
      confirming and broadening our understanding of the manner in which the cerebral
      cortex of humans contributes to respiratory control during volitional breathing.
      In the diencephalon, the integration of respiratory output in relation to changes
      in homeostasis occurs in the caudal hypothalamic region of mammals. Most
      importantly, neurons in this region are strongly sensitive to perturbations in
      oxygen tension which modulates their level of excitation. In addition, the caudal
      hypothalamus is a major site for 'central command', or the parallel activation of
      locomotion and respiration. Furthermore, midbrain regions such as the
      periaqueductal gray and mesencephalic locomotor region function in similar
      fashion as the caudal hypothalamus with regard to locomotion and more especially
      the defense reaction. Together these suprapontine regions exert a strong
      modulation upon the basic respiratory drive generated in the brainstem.

PMID- 9926986
TI  - Modulation of hypoxic ventilatory response by systemic platelet-activating factor
      receptor antagonist in the rat.
AB  - Platelet activating factor (PAF) has recently emerged as an important modulator
      of neuronal excitability by enhancing synaptic glutamate release. Since PAF
      receptors (PAFR) are ubiquitously distributed in the brain, we hypothesized that
      PAF may play a role in respiratory control. To examine this issue, hypoxic (10%
      O2 for 15 min, n = 14) and hypercapnic (5% CO2 for 30 min, n = 6) challenges were
      performed in chronically-instrumented, unrestrained adult rats following
      administration of the pre-synaptic PAFR antagonist BN52021 (i.p. 20 mg/kg in 0.5
      ml) or vehicle (Veh). In normoxia, BN52021 elicited VT decreases and
      corresponding f increases such that minute ventilation (VE) was unaffected.
      During hypercapnia, peak VE increased similarly after both treatments (103+/-18%
      in BN52021 vs. 94+/-19% in Veh, p-NS). In contrast, significant reductions in the
      peak hypoxic VE response occurred after BN52021 (42+/-10% vs. 104+/-18% in Veh,
      P<0.002). BN52021 increased normoxic arterial blood pressure and decreased heart
      rate. However, hypoxia-induced chronotropic responses were attenuated and
      depressor responses were enhanced by BN52021. We further examined protein kinase
      C (PKC) translocation patterns during acute hypoxia after systemic BN52021
      administration. Activation of PKC beta and delta was blocked by BN52021, PKC
      gamma was attenuated, with no effects on PKC alpha, epsilon, theta, iota, mu, and
      zeta. We conclude that systemic administration of a PAFR antagonist attenuates
      cardioventilatory recruitment to hypoxia and selectively attenuates activation of
      PKC in the rat brainstem. We speculate that enhanced regional PAF production and
      release during hypoxic conditions may contribute important excitatory inputs and
      signal transduction pathways within neuronal structures underlying cardiovascular
      and respiratory control.

PMID- 9926987
TI  - Attenuated respiratory compensation during rapidly incremented ramp exercise.
AB  - The fall in end-tidal and arterial P(CO2) may be delayed relative to the lactate
      threshold (LT) or absent, depending on the slope of the ramp exercise function.
      Ventilation (VE), gas exchange (V(O2), V(CO2)) and acid-base status were examined
      during slow (SR, 8 W x min(-1)) and fast (FR, 65 W x min(-1)) ramp cycle exercise
      in seven males. VE, V(O2), V(CO2), and end-tidal gas tensions (PETO2, PET(CO2))
      were determined breath-by-breath. Peak V(O2) (V(O2,peak)) was similar in SR and
      FR. V(CO2) and VE were similar during submaximal exercise. At V(O2,peak), VE was
      similar but V(CO2) was lower in SR than FR. With exercise, PET(CO2) increased at
      work rates below LT. At WRs > or =90%-V(O2,peak), PET(CO2) decreased below 0 W
      values in SR but not FR. Alveolar P(CO2)2 slope (PA(CO2)) increased with
      increasing WRs. Above LT, PA(CO2) was lower in SR than FR. Time of expiration
      (TE) decreased with increasing WRs, but no difference between SR and FR was
      observed. The higher PET(CO2) in FR at higher WRs was attributed in part, to a
      higher PA(CO2) as no differences were observed in TE.

PMID- 9926988
TI  - Respiratory pattern formation in the isolated bullfrog (Rana catesbeiana)
      brainstem-spinal cord.
AB  - This study characterizes various patterns of motor output obtained from cranial
      nerves V, VII, X, and XII of in vitro, saline-perfused, brainstem-spinal cord
      preparations of the American bullfrog (Rana catesbeiana). Motor output indicative
      of fictive breathing was present in all preparations. In 17 of 26 preparations,
      fictive breaths were either evenly spaced or randomly distributed, while in the
      remaining nine preparations fictive breaths occurred in episodes separated by
      relatively long periods of quiescence. With the exception of fictive breath
      duration in the non-episodic preparations and the instantaneous frequency of
      fictive breaths within episodes, all variables associated with fictive breathing
      were insensitive to changes in perfusion saline pH. In addition to fictive
      breathing, a large number of other forms of motor output were observed arising
      from these nerves. While the data suggest that the in vitro preparation is
      capable of producing a wide repertoire of motor patterns, similar to those seen
      in vivo, it was difficult, with the current protocol, to reliably produce any
      single pattern in spite of carefully regulated conditions.

PMID- 9926989
TI  - Assessment of respiratory system viscoelasticity in spontaneously breathing
      rabbits.
AB  - Airflow, volume (V), inspiratory time (TI), tracheal pressure (Ptr), abdomen
      (Dab) and rib cage diameters (Drc), peak diaphragm (Adi) and parasternal muscle
      activity (Aic) were measured in thirteen anaesthetized and vagotomized rabbits
      and in six vagotomized rabbits with cordotomy at T1 during unimpeded inspirations
      followed by rapid end-inspiratory airway occlusion, relaxation against closed
      airways, and inspiratory effort. To modify the inspiratory flow pattern, such
      sequences were performed at different volume, levels of chemical drive, and body
      temperatures (BT). Under all conditions, Adi, Aic, TI, Drc and Dab at iso-volume
      were the same for unimpeded and occluded inspirations; end-inspiratory Ptr was
      lower for occluded than for unimpeded inspirations, the difference (Pdiff) being
      larger the lower the volume at which occlusions were performed and the higher the
      chemical drive and BT. After paralysis, the viscoelastic constants of the
      respiratory system, modelled as a Kelvin body, were assessed according to the
      rapid airway occlusion method and used together with the inspiratory flow
      waveform to predict the end-inspiratory viscoelastic pressure (Pvisc) of
      unimpeded inspirations. Since the slope of the Pdiff vs. Pvisc relationship never
      differed from unity, Pdiff under the specified conditions should represent the
      effective Pvisc of unimpeded inspirations.

PMID- 9926990
TI  - Even moderate cigarette smoking influences the pattern of circulating monocytes
      and the concentration of sICAM-1.
AB  - The pattern of circulating monocyte subtypes and the concentration of the soluble
      intercellular adhesion molecule-1 (ICAM-1) were compared in middle-aged female
      moderate smokers and lifetime non-smokers. Total leukocyte and monocyte counts
      were higher in smokers. The pattern of circulating monocytes of smokers was
      changed toward lower absolute counts of activated (CD16+/CD64+) monocytes and
      (CD16+/CD14+) monocyte-macrophages and higher counts of nonactivated monocytes.
      The serum concentration of soluble ICAM-1 was significantly higher in smokers
      than in non-smokers. It is supposed that even moderate cigarette smoking leads to
      an activation of the circulating monocytes and their increased adhesion to the
      endothelium.

PMID- 9926991
TI  - Laminin inhibits Cl- -secretion across canine tracheal epithelium.
AB  - We examined the effect of laminin (a major component of the basement membrane) on
      potential difference (PD) and short circuit current (SCC) in both posterior
      epithelial membranes (native tissue) and cultured epithelial cell layers from
      canine trachea using an Ussing chamber. Although laminin itself did not alter the
      baseline values of SCC or PD, it significantly inhibited in a dose-dependent
      manner the isoproterenol induced SCC and PD rises of the epithelial membrane. In
      the cultured epithelial layer treated with amiloride, laminin did not alter the
      baseline values of SCC, PD or resistance (R) but it significantly inhibited the
      isoproterenol induced SCC rises. However, laminin did not significantly inhibit
      the bradykinin induced SCC rise in the cultured epithelial layer treated with
      amiloride. These findings indicate that laminin is a determinant in ion transport
      (mainly Cl- secretion) across canine tracheal epithelium, inhibiting the beta
      agonist induced Cl- transport.

PMID- 9926992
TI  - Physical characteristics and gas composition of nasal air affect nasal nitric
      oxide release.
AB  - We studied modulation of release of nitric oxide (NO) into nasal passages by
      physical characteristics (airflow, temperature, humidity) or gases (oxygen,
      carbon dioxide) in nasal air of humans. Each characteristic or gas in nasal air
      was changed during voluntary soft palate elevation (to isolate nasal passages).
      Increasing airflow through the nose caused incremental increases in NO release
      from 211+/-23 nl/(min x m(-2)) at 1 L/min to 312+/-40 nl/(min x m(-2)) at 22
      L/min (P<0.001, n = 6). Decreased humidity (dry airflow, 1-22 L/min) reduced NO
      release only at the highest airflow rate. Changing temperature (range 46 to 0
      degrees C) had no effect on NO release. Hypoxia (below 4% O2) rapidly and
      reversibly decreased NO release (200+/-40 nl/(min x m(-2)) at 21% O2 versus 99+/
      17 nl/(min x m(-2)) at 0% O2 for 3 min, (P<0.001, n = 5). Carbon dioxide (5%)
      reduced NO release slightly. We conclude that airflow, reduced humidity, carbon
      dioxide concentration, and oxygen concentration modulate NO release into nasal
      passages.

PMID- 9926993
TI  - CO2 and heat have different effects on directed ventilation behavior of
      grasshoppers Melanoplus differentialis.
AB  - We tested the hypothesis that CO2 and heat have different effects on the
      ventilatory pattern of grasshoppers Melanoplus differentialis. Eight grasshoppers
      were sealed between rostral (inspiratory) and caudal (expiratory) spiracles in
      separated, airtight, chambers and pressure changes were measured. Normal
      breathing patterns decreased pressure in the rostral chamber and increased
      pressure in the caudal chamber (i.e. unidirectional pumping rostral to caudal).
      Insects exposed to ventilatory stimulation by CO2 or heat significantly increased
      pumping frequency from 26+/-2 (+/-S.E.M.) at 0% CO2 to 54+/-6 breaths/min at 8%
      CO2 (at 30 degrees C), and from 27+/-3 at 30 degrees C to 44+/-4 breaths/min at
      45 degrees C. Unidirectional pumping failed to change with increased CO2
      concentration and increased significantly with heat exposure. Thus, while CO2
      only increased pumping frequency, heat increased pumping frequency and
      unidirectional pumping.

PMID- 9926994
TI  - Influence of temperature and pH on survival of Escherichia coli O157:H7 in dry
      foods and growth in reconstituted infant rice cereal.
AB  - Factors affecting the ability of Escherichia coli O157:H7 to survive in foods
      with a(w) less than required for growth have not been fully defined. This study
      was undertaken to determine the ability of E. coli O157:H7 to survive in a
      commercial dry infant rice cereal as affected by a(w) (0.35+/-0.04, 0.52+/-0.03
      and 0.73+/-0.03), pH (4.0 and 6.8), and temperature (5, 25, 35 and 45 degrees C),
      and in nine other reduced-a(w) foods. Death of E. coli O157:H7 in cereal was
      enhanced with increased temperature and decreased pH during a 16- to 24-week
      storage period. Survival was enhanced at pH 6.8 compared to pH 4.0 in cereal at
      a(w) 0.34+/-0.04 during initial storage at 5 and 25 degrees C. The effect of
      temperature (8, 15, 21 and 30 degrees C) on survival and growth of acid-adapted
      cells of E. coli O157:H7 inoculated into cereal reconstituted with milk or apple
      juice at two inoculum levels (8.2-12.3 cfu/ml and 82-123 cfu/ml of slurry) was
      also studied. Growth occurred in cereal reconstituted with milk at all test
      temperatures and in cereal reconstituted with apple juice at 15, 21 and 30
      degrees C. Populations increased by >1 log10 cfu/ml within 3-6 h at 21 and 30
      degrees C. Acid-adapted and unadapted cells had similar growth patterns. The
      effects of temperature and acid adaptation on survival of E. coli O157:H7 in nine
      commercial foods and food ingredients with pH 4.07-6.49 and a(w) 0.17-0.82 were
      determined. The pathogen survived in these foods for various lengths of time,
      depending the storage temperature, with an order of survival of 5 degrees C >21
      degrees C >37 degrees C. Survival appeared to be enhanced in foods with highest
      pH, and acid-adapted cells retained higher viability than unadapted cells in only
      two of the nine test foods. Of particular importance is the ability of E. coli
      O157:H7 to survive well in dry foods with a wide range in a(w) and pH,
      particularly at refrigeration temperature.

PMID- 9926995
TI  - Influence of acid tolerance responses on survival, growth, and thermal cross
      protection of Escherichia coli O157:H7 in acidified media and fruit juices.
AB  - A study was done to determine survival and growth characteristics of acid
      adapted, acid-shocked, and control cells of Escherichia coli O157:H7 inoculated
      into tryptic soy broth (TSB) acidified with organic acids and three commercial
      brands of apple cider and orange juice. The three types of cells behaved
      similarly in TSB acidified with acetic acid; however, in TSB (pH 3.9) acidified
      with lactic acid, acid-adapted cells were more tolerant than acid-shocked cells
      which, in turn, were more tolerant than control cells. The ability of the three
      types of cells to grow after inoculation into acidified TSB, then plated on
      tryptic soy agar containing sodium chloride was determined. Tolerance of acid
      adapted cells and, less markedly, acid-shocked cells to sodium chloride was
      diminished, compared to control cells. The pathogen showed extraordinary
      tolerance to the low pH of apple cider and orange juice held at 5 or 25 degrees C
      for up to 42 days. Growth occurred in one brand of apple cider (pH 3.98)
      incubated at 25 degrees C. Regardless of test parameters, there was no indication
      that cell types differed in tolerance to the acidic environment in apple cider or
      orange juice. Survival of control, acid-adapted, and acid-shocked cells heated in
      apple cider and orange juice was studied. Within each apple cider or orange
      juice, D(52 degrees C)-values of acid-adapted cells were considerably higher than
      those of acid-shocked or control cells, which indicates that heat tolerance can
      be substantially enhanced by acid adaptation compared to acid shock.

PMID- 9926996
TI  - Control of Yersinia enterocolitica in pigs at herd level.
AB  - A higher herd prevalence of antibodies (ELISA) to Yersinia enterocolitica O:3 was
      found in conventional slaughter production (86.0% seropositive herds) than in
      conventional farrow-to-finish herds (53.1% seropositive herds). The herd
      prevalence of antibodies to Y. enterocolitica in multiplying herds (56.1%) was
      similar to the level in the conventional farrow-to-finish herds. An
      epidemiological study in conventional pig herds demonstrated that farrow-to
      finish production (odds ratio, OR = 0.15) was an important protective factor.
      Using under-pressure ventilation (OR = 0.33) and manual feeding of slaughter pigs
      (OR = 0.44) also lowered the herd prevalence. The most expressed risk factor was
      using an own farm vehicle for transport of slaughter pigs to abattoirs (OR =
      12.92). Separation between clean and unclean section in herds (OR = 2.67), daily
      observations of a cat with kittens on the farm (OR = 2.41) and using straw
      bedding for slaughter pigs (OR = 2.25) were other factors that increased the
      risk. In conclusion, the epidemiological data suggest that it is possible to
      reduce the herd prevalence of Yersinia enterocolitica O:3 by minimising contact
      between infected herds and non-infected herds. Further, attempts to reduce the
      prevalence at the top levels of the breeding pyramids may be beneficial for the
      industry as a whole. The meat industry may use serological tests as a tool to
      lower the prevalence in the pig population by limiting the contact between
      seropositive and seronegative herds. However, because of the high prevalence of
      Y. enterocolitica in pig herds, a strict slaughter hygiene will remain an
      important means to reduce carcass contamination with Y. enterocolitica O:3 as
      well as other pathogenic micro-organisms.

PMID- 9926997
TI  - Comparison between ICS-Vidas, MSRV and standard cultural method for Salmonella
      recovery in poultry meat.
AB  - Two rapid methods for Salmonella detection, Vidas-ICS and modified semi-solid
      Rappaport-Vassiliadis (MSRV) were evaluated using contaminated poultry meat. The
      sensitivity and specificity of the methods were investigated on field samples and
      on artificially contaminated samples inoculated with mixtures of Salmonella and
      non-Salmonella competing strains. ICS-Vidas and MSRV yielded virtually identical
      results, in full agreement with the standard cultural method (SCM). The MSRV
      method showed better results with artificially contaminated samples, but was less
      sensitive than SCM when applied to field samples. The use of the MSRV and Vidas
      ICS methods could be particularly advantageous in the application of HACCP.

PMID- 9926998
TI  - Detection of Toxoplasma gondii in cured meats.
AB  - Congenital toxoplasmosis is associated with acute maternal infection acquired
      during or shortly before the pregnancy. The mother's infection is initiated by
      the ingestion of one of the life forms of the parasite but the relative
      importance of the different sources of toxoplasmosis are not established. Recent
      epidemiological studies have confirmed ingestion of raw meats as a risk factor
      but also identified consumption of cured meats as being associated with acute
      toxoplasmosis in pregnancy. There is little existing information concerning the
      efficiency of commercial curing processes for inactivating Toxoplasma gondii. We
      sought to detect the presence of T. gondii in ready-to-eat cured meat samples by
      amplification of the parasite's P30 gene using the polymerase chain reaction
      (PCR). In addition, tissue culture was used in order to isolate viable parasites.
      Laboratory inoculated specimens were used to assess the sensitivity of each
      method. PCR was able to detect parasite contamination down to a level of 5 x
      10(3) trophozoites/g while viable toxoplasma could be detected in tissue culture
      at a level of 10(3) trophozoites/g cured meat. The high salt content of some
      cured meats limited sensitivity of the PCR assay by inhibition of the polymerase
      enzyme and reduced the sensitivity of tissue culture due to osmotic pressure
      causing cytopathic effect. However viable T. gondii was detected in one out of 67
      ready-to-eat cured meat samples. Our results highlight the need for improved
      methods for detecting toxoplasma contamination of food. Health implications of
      consuming cured meats in pregnancy require careful consideration.

PMID- 9926999
TI  - Relationships among deoxynivalenol, ergosterol and Fusarium exoantigens in
      Canadian hard and soft wheat.
AB  - Soluble extracellular components (exoantigens) from cultures of Fusarium
      graminearum and F. sporotrichioides were used to produce antisera from chickens
      for an indirect enzyme immunoassay. This immunoassay was used to estimate
      Fusarium exoantigen levels in 40 samples of fusarium head blight-infected hard
      red spring wheat from Manitoba, and in 50 samples of infected soft white winter
      wheat from Ontario. These wheat samples were also assayed for deoxynivalenol
      (DON), the predominant Fusarium mycotoxin, and for ergosterol, a metabolite
      reflecting fungal biomass. Using F. sporotrichioides antisera, the linear
      correlations between exoantigen level and DON content for the hard and soft
      wheats had coefficients of 0.80 and 0.76, respectively. With the same antisera,
      linear correlations between exoantigen level and total ergosterol concentration
      for the hard and soft wheats had coefficients of 0.66 and 0.81, respectively.

PMID- 9927000
TI  - Lactic acid bacteria growth promoters from Spirulina platensis.
AB  - Spirulina has been used for many years as human food because of its high protein
      content and nutritional value. Some strains also produce bioactive substances
      that may inhibit or promote microbial growth. Lactococcus lactis, Streptococcus
      thermophilus, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus
      bulgaricus were grown in rich media, MRS and RM, as well as in minimal saline
      medium with and without addition of extracellular products obtained from a late
      log phase culture of Spirulina platensis in Zarrouk medium. In both MRS and RM
      media, the extracellular products significantly promote the growth of the lactic
      acid bacteria assayed. This stimulatory effect was observed in media with pH
      adjusted to 5.3, 6.3 and 7.0. No effect was observed in minimal saline medium.

PMID- 9927001
TI  - Virulence genes of Shiga toxin-producing Escherichia coli isolated from food,
      animals and humans.
AB  - The presence of virulence genes, encoding enterohemorrhagic Escherichia coli
      (EHEC)-hemolysin (EHEC-hlyA), intimin (eae), and Shiga toxins 1 (stx1) and 2
      (stx2), in 178 isolates of pathogenic E. coli, was determined using the
      polymerase chain reaction with primers specific for each virulence gene. The
      tested organisms were 120 isolates of E. coli O157:H7 from human patients,
      cattle, sheep and foods, 16 non-O157:H7 EHEC isolates from patients suffering
      from hemorrhagic colitis or hemolytic uremic syndrome, 15 non-O157:H7 Shiga toxin
      producing E. coli (STEC) isolates from cattle and foods, 26 isolates of
      enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC) and
      enterotoxigenic E. coli (ETEC), and an E. coli K12 strain. Results revealed that
      all isolates of O157:H7 carried EHEC-hlyA, eae, and one or both stx genes; 15 of
      the 16 non-O157:H7 EHEC isolates had EHEC-hlyA, but all possessed eae and one or
      both stx genes; only seven of the 15 non-O157 STEC isolated from cattle and foods
      contained both EHEC-hlyA and eae genes. The EPEC, EIEC, ETEC, and the E. coli K12
      strain did not carry these virulence genes, except eight EPEC isolates were
      positive for eae. Results suggest that a combination of EHEC-hlyA and eae genes
      could serve as markers to differentiate EHEC from less pathogenic STEC, and other
      pathogenic or non-pathogenic E. coli.

PMID- 9927003
TI  - Resistance training for health and disease: introduction.

PMID- 9927002
TI  - Naproxen does not alter indices of muscle damage in resistance-exercise trained
      men.
AB  - PURPOSE: Unaccustomed exercise is associated with an elevated plasma creatine
      kinase (CK), myofibrillar inflammation, and delayed onset muscle soreness (DOMS).
      Nonsteroidal antiinflammatory drugs (NSAID) may attenuate DOMS and indirect
      indices of inflammation in humans. METHODS: We studied the effects of an NSAID
      (naproxen sodium (500 mg, 2 times a day for 48 h)) taken before and after
      resistance exercise in eight healthy, moderately trained men in a randomized,
      double-blind trial. The exercise consisted of unilateral knee
      concentric/eccentric weight lifting with 6 sets x 10 repetitions at 80-85% of the
      1 repetition maximal contraction. Muscle biopsies of each vastus lateralis (EX =
      exercised/REST = control) were taken 24 h after exercise for immunohistochemical
      staining of inflammatory cells (leukocyte common antigen). At 24 and 48 h
      postexercise, we also determined DOMS, plasma CK activity, and knee extensor
      muscle torque. RESULTS: Exercise resulted in an increased CK activity at +24 and
      +48 h (vs preexercise: P < 0.01), with no treatment effect. There were no
      treatment effects for any of the measured variables except for a return of
      voluntary knee extension torque to baseline by +48 h postexercise for NSAID
      treatment (P < 0.05). CONCLUSIONS: NSAID administration did not alter CK rise,
      muscle force deficit at 24 h postexercise, nor perceived muscle pain. In
      addition, the increased CK at 24 h postexercise was not associated with an acute
      myofibrillar inflammatory cell infiltrate in moderately trained men after
      resistance exercise.

PMID- 9927004
TI  - Exercise training guidelines for the elderly.
AB  - The capacity of older men and women to adapt to increased levels of physical
      activity is preserved, even in the most elderly. Aerobic exercise results in
      improvements in functional capacity and reduced risk of developing Type II
      diabetes in the elderly. High-intensity resistance training (above 60% of the one
      repetition maximum) has been demonstrated to cause large increases in strength in
      the elderly. In addition, resistance training result in significant increases in
      muscle size in elderly men and women. Resistance training has also been shown to
      significantly increase energy requirements and insulin action of the elderly.
      PURPOSE: We have recently demonstrated that resistance training has a positive
      effect on multiple risk factors for osteoporotic fracture in previously sedentary
      postmenopausal women. METHODS: Because the sedentary lifestyle of a long-term
      care facility may exacerbate losses of muscle function, we have applied this same
      training program to frail, institutionalized elderly men and women. RESULTS: In a
      population of 100 nursing home residents, a randomly assigned high-intensity
      strength-training program resulted in significant gains in strength and
      functional status. In addition, spontaneous activity, measured by activity
      monitors, increased significantly in those participating in the exercise program
      whereas there was no change in the sedentary control group. Before the strength
      training intervention, the relationship of whole body potassium and leg strength
      was seen to be relatively weak (r2 = 0.29, P < 0.001), indicating that in the
      very old, muscle mass is an important but not the only determining factor of
      functional status. CONCLUSIONS: Thus, exercise may minimize or reverse the
      syndrome of physical frailty, which is so prevalent among the most elderly.
      Because of their low functional status and high incidence of chronic disease,
      there is no segment of the population that can benefit more from exercise than
      the elderly.

PMID- 9927005
TI  - Low back strengthening for the prevention and treatment of low back pain.
AB  - PURPOSE: Chronic low back pain (CLBP) remains one of the most difficult and
      costly medical problems in the industrialized world. A review of nineteenth and
      early twentieth century spine rehabilitation shows that back disorders were
      commonly treated with aggressive and specific progressive resistance exercise
      (PRE). Despite a lack of scientific evidence to support their efficacy,
      therapeutic approaches to back rehabilitation over the past 30 yr have focused
      primarily upon passive care for symptom relief. Recent spine rehabilitation
      programs have returned to active reconditioning PRE centered around low back
      strengthening to restore normal musculoskeletal function. Research has shown that
      lumbar extension exercise using PRE significantly increases strength and
      decreases pain in CLBP patients. It appears that isolated lumbar extension
      exercise with the pelvis stabilized using specialized equipment elicits the most
      favorable improvements in low back strength, muscle cross-sectional area, and
      vertebral bone mineral density (BMD). These improvements occur with a low
      training volume of 1 set of 8 to 15 repetitions performed to volitional fatigue
      one time per week. CLBP patients participating in isolated lumbar extension PRE
      programs demonstrate significant reductions in pain and symptoms associated with
      improved muscle strength, endurance, and joint mobility. Improvements occur
      independent of diagnosis, are long-lasting, and appear to result in less re
      utilization of the health care system than other more passive treatments. Low
      back strengthening shows promise for the reduction of industrial back injuries
      and associated costs.

PMID- 9927006
TI  - The effects of progressive resistance training on bone density: a review.
AB  - Osteoporosis is a major public health problem that is characterized by low bone
      mass and increased susceptibility to fractures, primarily of the hip, spine, and
      wrist. It is estimated to cause 1.5 million fractures annually in the United
      States in people aged 50 yr and older. Physical activity, particularly weight
      bearing exercise, is thought to provide the mechanical stimuli or "loading"
      important for the maintenance and improvement of bone health, whereas physical
      inactivity has been implicated in bone loss and its associated health costs. Both
      aerobic and resistance training exercise can provide weight-bearing stimulus to
      bone, yet research indicates that resistance training may have a more profound
      site specific effect than aerobic exercise. Over the past 10 years, nearly two
      dozen cross-sectional and longitudinal studies have shown a direct and positive
      relationship between the effects of resistance training and bone density.
      Conversely, a handful of other studies have reported little or no effect on bone
      density. However, these results may be partially attributable to the study
      design, intensity and duration of the exercise protocol, and the bone density
      measurement techniques used. High-intensity resistance training, in contrast to
      traditional pharmacological and nutritional approaches for improving bone health
      in older adults, has the added benefit of influencing multiple risk factors for
      osteoporosis including improved strength and balance and increased muscle mass.

PMID- 9927007
TI  - Acute responses to resistance training and safety.
AB  - Resistance training is widely used in fitness programs for healthy individuals of
      all ages and has become accepted as part of the exercise rehabilitation process
      for patients with coronary artery disease. It is only during the past decade that
      the acute circulatory responses to resistance exercise have been investigated
      directly, using intra-arterial measurement techniques and two-dimensional
      echocardiography. This review examines the factors that influence the acute
      circulatory responses to resistance training. These include the number of
      repetitions, the absolute and relative load, the muscle mass engaged in the
      lifting, the joint angle, and the Valsalva maneuver. There is discussion of the
      responses in patients with coronary artery disease and the effects of resistance
      training on the acute responses. The review ends with a discussion of the safety
      of this form of exercise and concludes that it is safe and appropriate for most
      healthy individuals and many of those with different diseases.

PMID- 9927008
TI  - Prescription of resistance training for health and disease.
AB  - When prescribed appropriately, resistance training is effective for developing
      fitness, health, and for the prevention and rehabilitation of orthopedic
      injuries. Because resistance training is an integral component in the
      comprehensive health program promoted by the major health organizations (e.g.,
      American College of Sports Medicine, American Heart Association, American
      Association of Cardiovascular and Cardiopulmonary Rehabilitation, Surgeon
      General's Office), population-specific guidelines have recently been published.
      The current research indicates that, for healthy persons of all ages and many
      patients with chronic diseases, single set programs of up to 15 repetitions
      performed a minimum of 2 d x wk(-1) are recommended. Each workout session should
      consist of 8-10 different exercises that train the major muscle groups. Single
      set programs are less time consuming and more cost efficient, which generally
      translates into improved program compliance. Further, single set programs are
      recommended for the above-mentioned populations because they produce most of the
      health and fitness benefits of multiple set programs. The goal of this type of
      program is to develop and maintain a significant amount of muscle mass,
      endurance, and strength to contribute to overall fitness and health. Patients
      with chronic diseases (e.g., arthritis) may have to limit range of motion for
      some exercises and use lighter weights with more repetitions.

PMID- 9927009
TI  - Youth ice hockey tournament injuries: rates and patterns compared to season play.
AB  - OBJECTIVE: To prospectively document the incidence of game injury rates in youth
      ice hockey tournaments to compare with season-long game injury rates and to
      analyze the injuries occurring at tournaments by mechanism, type, body location,
      severity, player position, and period of play. DESIGN: A prospective injury
      report form completed for injured players by the tournament athletic trainer.
      SETTING: Four boys' tournaments and one girls' tournament during the 1993-94
      season. PARTICIPANTS: 807 boys and girls, ages 9-19. MEASUREMENTS/MAIN RESULTS:
      60 injuries occurred in boys and 4 occurred in girls. There were 26 boys with
      significant injuries and no girls with significant injuries. The significant game
      injury rates per 1000 player hours were 50.9 for boys combined, 57.9 for boys'
      Peewee A, 42.7 for boys' Bantam A, 64.8 for boys' varsity high school, 44.8 for
      boys' Junior Gold, and 0 for girls' Peewee A and B. Cerebral concussion comprised
      15% of boys' injuries. CONCLUSIONS: The significant injury rate for boys'
      tournament game play was 4-6 times higher than the season game injury rates in
      two previous season-long studies. In boys' games, 65% of "all" injuries and 77%
      of "significant" injuries were related to collisions. The girls' rules of play do
      not allow body checking, and there were no significant injuries in girls' games.
      The boys had high rates of cerebral concussion injury at all age levels.
      Minimizing the frequency and intensity of collisions in the boys' game may
      decrease the injury rates, especially in the tournament setting.

PMID- 9927010
TI  - A simple, reliable method of assessing exercise capacity in patients with chronic
      heart failure.
AB  - OBJECTIVE: The accurate determination of limitations in physical activity is
      important in evaluating patients with heart failure and in assessing the efficacy
      of treatment. However, the conventional measures used to evaluate hemodynamics,
      functional class, and exercise capacity all have limitations. Our objective was
      to develop a simple method (The Master-Borg test) for evaluating the physical
      activity of patients with chronic heart failure using self-evaluation of the
      sensation of dyspnea at a constant workload. METHODS: Patients with NYHA class I
      (N = 20), class II (N = 20), and class III (N = 20) chronic heart failure
      performed a symptom-limited treadmill exercise test to determine peak VO2 and
      anaerobic threshold (AT). Patients subsequently performed Master's two-step test
      for 90 s and maximal dyspnea was self-rated using the visual analog Borg scale
      (the Master-Borg test). RESULTS: The mean workload in the Master-Borg test was
      15.2+/-1.6 mL x min(-1) x kg(-1). A significant correlation was found between the
      Master-Borg score and peak VO2 (r = 0.87) or AT (r = 0.84). The reproducibility
      of the Master-Borg tests was represented by a correlation coefficient of 0.93.
      CONCLUSION: Although simple and inexpensive, the Master-Borg test accurately
      represents ordinary activity levels, relates the sensation of dyspnea to peak
      exercise tolerance, and can be completed by most patients with heart failure.
      Master-Borg scores correlated with peak VO2 and AT, and can differentiate among
      NYHA classes I, II, and III. The Master-Borg test appears to be clinically useful
      for evaluating the value of physical activity and exercise capacity of patients
      with chronic heart failure.

PMID- 9927011
TI  - Exercise and cellular innate immune function.
AB  - Epidemiological evidence suggests a link between the intensity of exercise and
      infectious and neoplastic disease. One likely way by which exercise exerts its
      effect on cancer and infection is by altering the function of the immune system.
      Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK]
      cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against
      cancer and infectious disease by nature of their phagocytic, cytolytic, and
      antimicrobial properties. The purpose of this review is to define the role of
      cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection
      and cancer, present current information regarding the effects of acute and
      chronic exercise on the quantification and functional activities of these cells,
      and briefly to discuss potential mechanisms as to how exercise affects these
      cells and describe how these changes may potentially affect susceptibility to
      infection and cancer. The effects of exercise on the number, functions, and
      characteristics of cells of the innate immune system are complex and are
      dependent several factors, including 1) the cell function or characteristic being
      analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of
      measurement in relation to the exercise bout; 4) the dose and type of
      immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site
      of cellular origin. Further studies are needed to determine whether the exercise
      induced changes in immune function alter incidence or progression of disease.
      Likewise, the mechanisms as to how exercise alters innate immune function are as
      yet unresolved.

PMID- 9927012
TI  - Salivary IgA levels and infection risk in elite swimmers.
AB  - The effects of exercise on the immune system has been shown to be dependent on
      the level of fitness of the subjects, the degree of intensity, and the duration
      of the exercise. A reduction in salivary IgA levels occurs after individual
      sessions of exercise. PURPOSE: The purpose of this study was to assess the
      relationship between changes in salivary IgA and training volume, psychological
      stress, and infection rates in a cohort of 26 elite swimmers over a 7-month
      training period and to compare the changes with a group of 12 moderately
      exercising controls. METHODS: Salivary IgA concentrations were measured by an
      electroimmunodiffusion. Exercise gradings were assessed by a standardized aerobic
      anaerobic rating system. Psychological stress/anxiety was evaluated by the
      Spielberger State-Trait Anxiety Inventory. Infections were physician-verified.
      RESULTS: Salivary IgA levels showed an inverse correlation with the number of
      infections in both elite swimmers and moderately exercising control subjects. The
      pretraining salivary IgA levels in swimmers were 4.1% lower for each additional
      month of training and 5.8% lower for each additional infection. The posttraining
      salivary IgA levels in swimmers were not significantly correlated with infection
      rates but were 8.5% lower for each additional 1 km swum in a training session and
      7.0% lower for each additional month of training. The number of infections
      observed in the elite swimmers was predicted from regression models by the
      preseason (P = 0.05) and the mean pretraining salivary IgA levels (P = 0.006).
      The trends in pretraining salivary IgA levels over the 7-month season, calculated
      as individual slopes of pretraining IgA levels over time, were also predictive of
      the number of infections (P = 0.03) in the swimmers. CONCLUSIONS: These results
      indicate that measurement of salivary IgA levels over a training season may be
      predictive for athletes at risk of infection.

PMID- 9927013
TI  - Lymphocyte subpopulations in lymphoid organs of rats after acute resistance
      exercise.
AB  - PURPOSE: The ability of aerobic exercise to change lymphocyte subpopulation
      distributions is well documented; much less is known about resistance exercise.
      The purpose of this experiment was to determine the effects of an acute bout of
      resistance exercise on lymphocyte subpopulations in primary and secondary
      lymphoid compartments. METHODS: Male rats were operantly conditioned to climb a
      ladder while carrying weights that were progressively increased to equal body
      weight. During the acute session, rats performed repetitive climbs until
      exhaustion. Thymus, spleen, blood, and axial and inguinal lymph nodes were
      removed; leukocytes were isolated and incubated with monoclonal antibodies
      against differentiation markers, activation antigens, and adhesion molecules.
      RESULTS: Exercised versus control rats had greater numbers of leukocytes in the
      thymus, axial, and inguinal nodes but not in the blood or spleen. The percentage
      of CD4+ cells increased after exercise in the thymus, spleen, and blood. The
      percentages of cells expressing the integrin LFA-1beta were elevated in all the
      tissues except inguinal lymph nodes. In addition, more leukocytes from exercised
      than nonexercised rats expressed detectable numbers of activation markers, IL-2
      receptor-alpha and MHC class II molecules; however, as indicated by proliferating
      cell nuclear antigen analysis, the cells were not actively dividing at the time
      of assay. CONCLUSIONS: Based on these and published data, it appears that a
      single bout of resistance exercise can affect lymphoid cell subpopulations
      probably by inducing changes in leukocyte trafficking.

PMID- 9927014
TI  - Substrate utilization and glucose turnover during exercise of varying intensities
      in individuals with NIDDM.
AB  - PURPOSE: This investigation was undertaken to examine substrate utilization and
      glucose turnover during exercise of varying intensities in NIDDM patients.
      METHODS: Six male NIDDM patients (N) and six male controls (C) of similar age,
      body weight, % body fat, and VO2peak were studied in two experimental sessions
      administered in a randomized counterbalanced order. During each session the
      subjects cycled at a power output corresponding to 50% of VO2peak or 70% of
      VO2peak. Duration of exercise was adjusted so that energy expenditure (EE) was
      equal in both the 50% and 70% trials. Isotope infusion technique and indirect
      calorimetry were used to assess substrate utilization and glucose turnover during
      exercise. RESULTS: Rates of carbohydrate (CHO) and lipid oxidation increased (P <
      0.05) during both the 50% and 70% trials. Rates of CHO oxidation were greater (P
      < 0.05) during the 70% than during the 50% trial. However, rates of lipid
      oxidation were similar in the two trials. No differences in rates of CHO and
      lipid oxidation were observed in N and C. Rates of hepatic glucose production
      (Ra) and plasma glucose utilization (Rd) increased (P < 0.05) during exercise,
      and the increases were similar in the 50% and 70% trials. Ra did not differ
      between N and C. However, Rd was greater (P < 0.05) in N than in C. Plasma
      glucose concentration decreased (P < 0.05) in N, with the decrease being similar
      in the 50% and 70% trials. In contrast, plasma glucose concentration remained
      unchanged during both the 50% and 70% trials in C. CONCLUSIONS: Exercise results
      in a greater increase in plasma glucose utilization in patients with NIDDM
      compared with that in normal individuals, and this increase mediates the decline
      in plasma glucose concentrations in patients with NIDDM. Under isocaloric
      conditions, the changes in plasma glucose utilization and plasma glucose
      concentrations are similar during exercise of varying intensities. Despite a
      greater glucose utilization, carbohydrate and fat oxidation are similar in the
      two groups and their relations to exercise intensity are not altered by NIDDM.

PMID- 9927015
TI  - Muscle oxygenation trends during constant work rate cycle exercise in men and
      women.
AB  - PURPOSE: To examine the relationship between muscle oxygenation and arteriovenous
      oxygen difference [(a - v)O2diff)] at four constant rate workloads in healthy men
      and women and to compare these responses between the genders. METHODS: Nineteen
      men and 14 women consented to perform an incremental test to identify the lactic
      acidosis threshold (LAT) and maximal aerobic power (VO2max) and an intermittent
      constant work rate test at an oxygen uptake corresponding to 40% LAT, 80% LAT,
      25% LAT-VO2max, and 50% LAT-VO2max. Each exercise interval was 5 min long
      followed by 2 min of recovery. Cardiac output was measured by CO2 rebreathing at
      each workload from which (a - v)O2diff was computed. Tissue absorbency was
      measured from the vastus lateralis in both the test sessions using near infrared
      spectroscopy (NIRS). Muscle oxygenation during constant work rate exercise and
      recovery was expressed as a percentage (%Mox) of the maximum range observed
      during incremental exercise and recovery. RESULTS: A systematic decrease was
      observed in %Mox with increasing intensity, followed by a proportional increase
      during recovery from each exercise bout. Significant inverse relationships were
      observed between %Mox and (a - v)O2diff in men (r = -0.34) and women (r = -0.31)
      across the four intensities. Mean %Mox was significantly higher (P < 0.05) in
      women compared with men, suggesting lesser deoxygenation at the same relative
      exercise intensity. CONCLUSIONS: %Mox was not an accurate predictor of mixed (a -
      v)O2diff during exercise because of the low common variance between these two
      variables, and it is unclear whether the gender difference in %Mox is a true
      physiological phenomenon or whether it is an artifact of the NIRS technique.

PMID- 9927016
TI  - The effect of repeat exercise on pulmonary diffusing capacity and EIH in trained
      athletes.
AB  - PURPOSE: The purpose of this study was to determine the effects of repeated heavy
      exercise on postexercise pulmonary diffusing capacity (DL) and the development of
      exercise induced arterial hypoxemia (EIH). METHODS: 13 endurance-trained, male
      athletes (age = 27+/-3 yr, height = 179.6+/-5.0 cm, weight = 71.8+/-6.9 kg,
      VO2max = 67.0+/-3.6 mL x kg(-1) x min(-1) performed two consecutive, continuous
      exercise tests on a cycle ergometer to VO2max, separated by 60 min of recovery.
      Arterial oxygen saturation (%SaO2) was measured via ear oximetry, and resting DL
      was measured and partitioned by the single-breath method, before exercise and 60
      min after each exercise bout. RESULTS: No significant differences resulted in
      VO2max, VE, peak heart rate (HR), or breathing frequency between exercise bouts
      (P > 0.05). There was a small but significant decrease (454-446 W; P < 0.05) in
      peak power output in the second test. %SaO2 decreased from resting values during
      both exercise tasks, but there was no difference between the minimum saturation
      achieved in test 1 (91.4) or test 2 (91.6; P > 0.05). After the initial exercise
      bout, significant decreases (P < 0.05) occurred in DL (11%), membrane diffusing
      capacity (DM) (11%) and pulmonary capillary volume (VC) (10%). Further decreases
      occurred in DL (6%; P < 0.05), DM (2%; P > 0.05), and VC (10%; P < 0.05) after
      the second exercise bout. CONCLUSIONS: These observations question the meaning of
      post exercise measurements of pulmonary diffusion capacity, and its components,
      relative to pulmonary gas exchange and pulmonary fluid accumulation during
      exercise. The fact that there was no further change in %SaO2 after the second
      test suggests that if any interstitial edema developed, it was of no clinical
      significance; alternatively, the changes in DL(CO) may be related more to
      redistribution of blood than the development of pulmonary edema.

PMID- 9927017
TI  - Does exercise intensity or diet influence lactic acid accumulation in breast
      milk?
AB  - PURPOSE: This study examined the relationships among diet, exercise intensity,
      and breast milk composition in lactating women. METHODS: Twelve lactating women
      were randomly assigned to either a high (N = 6; 5.03 g carbohydrate (CHO) x kg
      body mass (BM)(-1)) or moderate (N = 6; 3.89 g CHO x kg BM(-1)) carbohydrate
      diet. Milk and blood samples were collected before and after a nonexercise
      session (control) and maximal, lactic acid-threshold (LAT), and 20% below the LAT
      (LAT-20) intensities. RESULTS: The 30-min exercise LAT bout was more stressful
      than the 30-min LAT-20 bout (rating of perceived exertion (RPE) = 15 vs 12,
      respectively, P < 0.05). Milk LA was significantly higher at 0 min following
      maximal exercise in the high and moderate CHO groups (1.27+/-0.56 and 1.52+/-0.49
      mM, respectively) and following LAT exercise (0.19+/-0.16 and 0.25+/-0.12 mM,
      respectively), when compared with the control session (0.08+/-0.03 and 0.09+/
      0.05 mM, respectively). This was not observed following the LAT-20 exercise in
      the high and moderate CHO groups (0.11+/-0.04 and 0.12+/-0.08 mM, respectively).
      Elevated milk LA persisted in the 30-min collection point after maximal exercise
      only. There was no significant effect of dietary treatment on milk or blood LA at
      any of the collection points. CONCLUSIONS: In lactating women whose caloric needs
      are being met: 1) dietary CHO intake, within a practical range, does not
      influence LA levels in breast milk at rest or after exercise; 2) LA appearance in
      the milk is a function of exercise intensity; and 3) moderate intensity exercise
      (RPE = 12) will not increase breast milk LA levels.

PMID- 9927018
TI  - Daily primary school physical education: effects on physical activity during
      adult life.
AB  - PURPOSE: The purpose of this investigation was to study the influence of a daily
      primary school physical education program on physical activity (PA) level,
      attitudes toward physical activity, and perceptions of barriers to physical
      activity during adulthood. METHODS: We compared two groups: 1) an experimental
      group of men and women (N = 147) who had received five physical education
      sessions per week throughout their 6 yr of primary school education in the early
      1970s; and 2) a control group, drawn from the data bank of the Quebec Health
      Survey, and matched for age, gender, and socioeconomic profile (N = 720).
      Experimental and control subjects filled out an identical questionnaire about
      their current physical activity level, their attitudes toward PA, and their
      perceptions of barriers to PA. The control group was stratified to obtain the
      same sociodemographic profile as the experimental group. RESULTS: Our principal
      results were: 1) a frequency distribution that showed a higher rate of physical
      activity in experimental women than in control women; 2) similar intentions to
      exercise and attitudes toward exercise in the experimental and control groups,
      with no differences in opportunities for exercising or in the support received
      from their family and friends; and 3) a lower prevalence of regular smokers in
      experimental men than in control men. There were also some differences in the
      types and frequency of physical activities selected between experimental and
      control subjects. CONCLUSION: Our results strongly suggest that daily physical
      education at the primary school level has had a significant long-term positive
      effect on the exercise habits on women, despite similar perceived barriers,
      attitudes, and intention to exercise in the two groups. The program has also had
      a significant health effect in men, substantially reducing the risk of becoming a
      regular smoker. Because the program was not specifically designed to promote
      health, we hypothesize that a health-oriented physical education program could
      have an even stronger effect.

PMID- 9927019
TI  - Childhood and adolescent physical activity patterns and adult physical activity.
AB  - PURPOSE: A major research priority is the influence of childhood and adolescent
      physical activity patterns on adult physical activity. The research in this area
      is inconsistent. Therefore, the purpose of this study was to evaluate the
      relationships among specific components of physical activity during childhood and
      adolescence and exercise habits in adulthood. METHODS: We analyzed preteen and
      teenage experiences, individual and team sports, and several psychosocial
      variables. One hundred and five male volunteers completed questionnaires about
      their current (estimated energy expenditure (EE)) and historic physical activity
      and a treadmill stress test. RESULTS: Based on correlations and regression
      analyses, without and with controlling for potentially confounding variables
      (treadmill run time and sum of skinfolds), the frequency of being forced to
      exercise and the frequency of being encouraged to exercise during the preteen
      years were inversely related to adult physical activity. Being forced to exercise
      during the preteen years was more related to participation in individual sports
      than to participation in team sports or both individual and team sports.
      CONCLUSIONS: Being forced to exercise during childhood may have potentially
      negative consequences for later activity. The findings indicate that experiences
      related to participation in activity during childhood and adolescence may
      influence adult physical activity. The implications of our findings are discussed
      and future research is recommended.

PMID- 9927020
TI  - Neuromuscular characteristics and muscle power as determinants of 5-km running
      performance.
AB  - PURPOSE: The purpose of this study was to investigate neuromuscular
      characteristics and muscle power as determinants of distance running performance.
      METHODS: Seventeen male endurance athletes performed a 5-km time trial (5K) that
      included three separate constant-velocity 200-m laps during the course and a
      maximal 20-m speed (V20m) test on an indoor track, and running economy (RE) tests
      on a treadmill and on the track. Maximal anaerobic (MART) and aerobic running
      tests on the treadmill were used to determine maximal velocity in the MART
      (VMART), maximal oxygen uptake (VO2max), peak treadmill performance (VO2max
      demand), and respiratory compensation threshold (RCT). RESULTS: Velocity in the
      5K (V5K) correlated positively (P < 0.05) with VO2max, VO2max demand, RCT, and
      RE, as well as with V20m and VMART. Regression analysis showed that RCT, track
      RE, and VMART were the most important determinants of V5K. V5K also correlated (P
      < 0.05) with contact times (CT) and stride rates in the maximal 20-m run (r = 
      0.49 and 0.58, respectively), as well as with the mean CT of the constant
      velocity laps during the 5K (r = -0.50). VMART correlated significantly with peak
      blood lactate concentration in MART (r = 0.59, P < 0.05), V20m (r = 0.87, P <
      0.001), and CT in the maximal 20-m run (r = -0.61, P < 0.01). CONCLUSIONS: We
      conclude that neuromuscular characteristics and VMART were related to 5-km
      running performance in well trained endurance athletes. Relationships between
      VMART and neuromuscular and anaerobic characteristics suggest that VMART can be
      used as a measure of muscle power in endurance athletes.

PMID- 9927021
TI  - An analysis of hip joint loading during walking, running, and skiing.
AB  - PURPOSE: It was the purpose of this study to investigate loading of the hip joint
      during various skiing activities and to compare the results with walking and
      running. The results are relevant to determine which skiing activities can be
      recommended for patients after total hip replacement. METHODS: Nine male subjects
      were instrumented with a 12-channel accelerometer system mounted on the upper
      body. Data were collected during walking, running, and six skiing activities and
      used as input for an inverse dynamic analysis that resulted in the time histories
      of the intersegmental force and moment at the supporting hip joint. Joint contact
      force was computed using a simple muscle model. Peak values were determined,
      averaged over all loading cycles, and compared between activities. RESULTS:
      Intersegmental force, indicating the influence of upper body weight and
      accelerations, was highest during running. Intersegmental moments were highest
      during the alpine skiing activities and indicated large extensor muscle forces at
      the hip joint. The peak joint contact force during walking at 1.5 m x s(-1) was
      2.5+/-0.3 times body weight (BW). Running at 3.5 m x s(-1) produced a joint
      contact force of 5.2+/-0.4 BW during the push-off phase. Joint contact forces
      during four different alpine skiing conditions ranged from 4.1+/-0.6 BW (long
      turns, flat slope) to 7.8+/-1.5 BW (short turns, steep slope). Cross-country
      skiing had lower hip joint loading than running but higher than walking: 4.0+/
      1.1 BW for classical technique and 4.6+/-0.6 BW for skating technique.
      CONCLUSIONS: Assuming that walking is a "safe" activity for a hip prosthetic
      patient, controlled alpine skiing and cross-country skiing appear relatively safe
      with respect to the magnitude of loading. However, the skiing activities showed
      considerably higher mediolateral and anterior-posterior forces than walking.
      Mechanical testing of prosthetic devices with loading conditions specific to
      these activities is needed to assess the effect of these force components on hip
      prostheses and to allow interpretation with respect to potential effects of
      skiing for a hip prosthetic patient.

PMID- 9927022
TI  - Effect of physical training on total and visceral fat in obese children.
AB  - PURPOSE: Children with high levels of total body fat mass (TFM) and visceral
      adipose tissue (VAT) have elevated levels of certain risk factors for coronary
      artery disease and non-insulin-dependent diabetes mellitus. We tested the
      hypothesis that controlled physical training, without dietary intervention, would
      have a favorable impact on VAT and percent body fat (%BF) in obese children.
      METHODS: A volunteer sample of 74 obese children, 7-11 yr of age, accepted random
      assignment to physical training or control groups. Before and after 4 months of
      intervention, measurements were obtained for VAT, TFM, %BF, daily physical
      activity, and cardiovascular fitness. The intervention involved 4 months of
      controlled physical training 5 d x wk(-1), 40 min per session, at a mean heart
      rate (HR) of 157 beats x min(-1). The estimated energy expenditure (EE) per
      training session was 925+/-201 kJ. RESULTS: Compared with the control group, the
      physical training group declined significantly in %BF (delta = -2.2%) (P < 0.01),
      TFM (delta = -3.1%) (P < 0.01), and subcutaneous abdominal adipose tissue (delta
      = - 16.1%) (P < 0.05), and increased significantly in fat-free mass (delta =
      +6.1%) (P < 0.05) and moderate-to-very hard physical activity (delta = +14.1%) (P
      < 0.05). The increase in VAT was significantly less in the physical training
      group (delta = +0.5%) as compared with that in the control group (delta = +8.1%)
      (P < 0.05). CONCLUSIONS: This study showed that during physical training obese
      children: 1) were capable of participating in a substantial amount of high
      intensity physical training over a 4-month period: 2) accumulated significantly
      less VAT as compared with nonexercising controls; and 3) experienced other
      beneficial changes in total and regional body composition.

PMID- 9927023
TI  - Influence of low and high dietary fat on physical performance in untrained males.
AB  - PURPOSE: Dietary manipulations have been used in athletes to enhance aerobic
      performance. We intended to verify whether the quality of energy substrate
      provided by food (percentage of total calories from fat and carbohydrates) per se
      has the ability to affect aerobic performance in sedentary humans. METHOD:
      Fourteen healthy sedentary males were sequentially submitted to 4-wk eucaloric
      diets (spontaneous diet: 30% of total calories from fat; low-fat, 15% fat; high
      fat, 55% fat; and spontaneous, 30% fat). After each diet period, individual body
      mass, percentage body fat (plicometry), VO2max (incremental bicycle-ergometry)
      and endurance (pedaling time to exhaustion at 75%VO2max) were measured. VO2,
      VCO2, VE, R, and heart rate (HR) were measured at rest and during exercise tests.
      Body composition and performance data (VO2max and endurance) were compared for
      significant differences by repeated measures ANOVA. RESULTS: Subjects' body
      weight, percentage body fat, and fitness status (indicated by intercept and slope
      of the HR/VO2 linear relationship) did not change significantly during the study,
      thus ruling out the influence of these potential confounders. For a given
      workload, VO2, VE, and R were unaffected by diet composition. VO2max and
      endurance time were not significantly modified by the different diets.
      CONCLUSIONS: Our study showed no impact, positive or negative, of diet's
      macronutrient composition on physical performance. It appears that the quality of
      energy substrate provided by food does not have the ability to affect either
      maximal or submaximal aerobic performance in untrained individuals.

PMID- 9927024
TI  - Interval training at VO2max: effects on aerobic performance and overtraining
      markers.
AB  - PURPOSE: Between inefficient training and overtraining, an appropriate training
      stimulus (in terms of intensity and duration) has to be determined in accordance
      with individual capacities. Interval training at the minimal velocity associated
      with VO2max (vVO2max) allows an athlete to run for as long as possible at VO2max.
      Nevertheless, we don't know the influence of a defined increase in training
      volume at vVO2max on aerobic performance, noradrenaline, and heart rate. METHODS:
      Eight subjects performed 4 wk of normal training (NT) with one session per week
      at vVO2max, i.e., five repetitions run at 50% of the time limit at vVO2max, with
      recovery of the same duration at 60% vVO2max. They then performed 4 wk of
      overload training (OT) with three interval training sessions at vVO2max. RESULTS:
      Normal training significantly improved their velocity associated with VO2max
      (20.5+/-0.7 vs 21.1+/-0.8 km x h(-1), P = 0.02). As a result of improved running
      economy (50.6+/-3.5 vs 47.5+/-2.4 mL x min(-1) x kg(-1), P = 0.02), VO2max was
      not significantly different (71.6+/-4.8 vs 72.7+/-4.8 mL x min(-1) x kg(-1)).
      Time to exhaustion at vVO2max was not significantly different (301+/-56 vs 283+/
      41 s) as was performance (i.e., distance limit run at vVO2max: 2052.2+/-331 vs
      1986.2+/-252.9 m). Heart rate at 14 km x h(-1) decreased significantly after NT
      (162+/-16 vs 155+/-18 bpm, P < 0.01). Lactate threshold remained the same after
      normal training (84.1+/-4.8% vVO2max). Overload training changed neither the
      performance nor the factors concerning performance. However, the submaximal heart
      rate measured at 14 km x h(-1) decreased after overload training (155+/-18 vs
      150+/-15 bpm). The maximal heart rate was not significantly different after NT
      and OT (199+/-9.5, 198+/-11, 194+/-10.4, P = 0.1). Resting plasma norepinephrine
      (veinous blood sample measured by high pressure liquid chromatography), was
      unchanged (2.6 vs 2.4 nm x L(-1), P = 0.8). However, plasma norepinephrine
      measured at the end of the vVO2max test increased significantly (11.1 vs 26.0 nm
      x L(-1), P = 0.002). CONCLUSION: Performance and aerobic factors associated with
      the performance were not altered by the 4 wk of intensive training at vVO2max
      despite the increase of plasma noradrenaline.

PMID- 9927025
TI  - Pre-exercise carbohydrate meals: application of glycemic index.
AB  - PURPOSE: The purpose of this study was to compare postprandial glycemic,
      insulinemic, and physiologic responses to a pre-exercise meal calculated to have
      a low glycemic index (LGI) with one calculated to have a moderately high glycemic
      index (HGI); each meal provided three foods totaling 1.5 g carbohydrate/kg body
      weight. METHODS: After an overnight fast, 10 trained cyclists consumed one of the
      test meals or water 30 min before cycling 2 h at 70% of maximum oxygen uptake
      (VO2max), followed by cycling to exhaustion at 100% of VO2max. RESULTS: Plasma
      insulin levels were significantly lower (P < 0.05) after LGI than after HGI
      through 20 min of exercise. Significantly higher (P < 0.05) respiratory exchange
      ratios were observed after HGI than after LGI until 2 h of exercise. At that time
      plasma glucose levels were significantly higher and ratings of perceived exertion
      lower (P < 0.05) after LGI compared with after HGI. Time to exhaustion was 59%
      longer after LGI (206.5+/-43.5 s) than after HGI (129.5+/-22.8 s). CONCLUSIONS:
      These results suggest a pre-exercise LGI may positively affect maximal
      performance following sustained exercise. The LGI maintained higher plasma
      glucose levels at the end of 2 h of strenuous exercise than the HGI, which may
      have better supported subsequent maximal effort.

PMID- 9927026
TI  - Comparison of accelerometers with oxygen consumption in older adults during
      exercise.
AB  - PURPOSE: The purpose of this study was to compare two commercially available
      accelerometers with indirect calorimetry in a group of older adults (x +/- SD;
      70.6+/-3.7 yr; N = 86, 44 males and 42 females). METHODS: The accelerometers
      (Caltrac and Tritrac, Hemokinetics, Madison, WI) were worn while performing three
      submaximal, discontinuous (5 min exercise, 2 min recovery), progressive levels of
      treadmill walking and bench stepping. The treadmill exercise averaged 3.4 mph, at
      0.4% grade, 3.0% grade, and 5.1% grade, while the stepping work rates (24 steps x
      min(-1)) were performed on 15.2-, 20.3-, and 25.4-cm steps. Estimated energy
      expenditure (EE) from the two accelerometers was compared with EE as measured by
      indirect calorimetry. RESULTS: The Caltrac significantly (P < 0.05) overestimated
      EE at the three treadmill work rates (10-52% difference) and underestimated EE at
      the three stepping work rates (-19% to -28% difference). When comparing the
      changes in EE between work rates one, two and three, the Caltrac was not
      sensitive to the changes (increase in EE) that occurred during graded treadmill
      walking but did detect some changes in the stepping exercise. The Tritrac
      significantly (P < 0.05) underestimated EE for the three work rates of both the
      treadmill and stepping exercise when compared with indirect calorimetry but did
      detect differences in EE among work rates during stepping exercise (P < 0.05).
      CONCLUSIONS: These data indicate that the magnitude of the differences between
      measured and estimated EE is affected by exercise mode and intensity and that
      caution is warranted when using the accelerometers in an attempt to quantify EE
      in older adults.

PMID- 9927027
TI  - The North Carolina High School Athletic Injury Study: design and methodology.
AB  - PURPOSE: Organized interscholastic athletics are an integral part of the
      educational program at almost every school level. With this growing popularity of
      sports and their inclusion in more public school programs, it becomes
      increasingly apparent that additional consideration must be given to the injury
      problem associated with sport. The North Carolina High School Athletic Injury
      Study (NCHSAIS) was undertaken to identify patterns of injury among male and
      female athletes in North Carolina high schools participating in any of 12 sports.
      Specific aims are to measure the incidence, severity and etiology of injuries; to
      determine the relationship of demographic factors and protective equipment,
      exposure to play, and school characteristics to injuries; to study the
      relationship of coaches' training and experience to injury occurrence; and to
      compare the incidence and severity of injury among female and male athletes in
      the same or comparable sports. METHODS: A two-stage cluster sample of 100 high
      schools in North Carolina was selected for this 4-yr prospective study. RESULTS:
      Participation by the initial sample or a random replacement was achieved for 91
      of the 100 schools. Nonresponse occurred at multiple levels of the sample for
      this study, and the weekly participation form posed the greatest respondent
      burden. CONCLUSIONS: The NCHSIAS offers a successful methodology for addressing
      sports injuries. In this paper we describe the design, methodology, and
      implementation issues that emerge in conducting a large scale epidemiological
      study in a population of high school athletes.

PMID- 9927028
TI  - Accuracy of prediction equations to estimate submaximal VO2 during cycle
      ergometry: the HERITAGE Family Study.
AB  - It was hypothesized that more accurate equations for estimating submaximal VO2
      during cycle ergometry could be developed if more independent variables were used
      in the equation. PURPOSE: The purposes of this study were: (1) to develop new
      equations for estimating submaximal VO2 during cycle ergometry; and (2) to
      examine the accuracy of the newly developed equations and those of the American
      College of Sports Medicine (1995), Berry et al. (1993), Lang et al. (1992), Latin
      and Berg (1994), and Londeree et al. (1997). METHODS: Subjects (715 men and
      women, ages 16-65 yr, from the HERITAGE Family Study) completed a maximal cycle
      ergometry test, two submaximal trials at 50 W and 60% of VO2max, hydrostatic
      weighing, and stature and body mass measures before and after 20 wk of cycle
      ergometry training. Regression analysis generated prediction equations using
      pretraining data from the 60% trials. RESULTS: No equation with more independent
      variables was better than an equation that used only power output. This equation,
      HERITAGE-1, with only power output was cross-validated using the "jackknife"
      technique. Paired t-tests, mean differences, SEEs, and Es were used to compare
      the VO2 estimated by HERITAGE-1 and those of previously published equations with
      the measured VO2 at 60% of VO2max. CONCLUSIONS: HERITAGE-1 was slightly better
      than the equations of ACSM, Lang et al., and Latin and Berg using pretraining
      data but was not better when using post-training data. All four of these
      equations were superior to the equations of Berry et al. and Londeree et al.

PMID- 9927029
TI  - Childhood hepatoblastomas frequently carry a mutated degradation targeting box of
      the beta-catenin gene.
AB  - Hepatoblastomas (HBs) are embryonal tumors affecting young children and
      representing the most frequent malignant liver tumors in childhood. The molecular
      pathogenesis of HB is poorly understood. Although most cases are sporadic, the
      incidence is highly elevated in patients with familial adenomatous polyposis
      coli. These patients carry germline mutations of the APC tumor suppressor gene.
      APC controls the degradation of the oncogene product beta-catenin after its NH2
      terminal phosphorylation on serine/threonine residues. APC, as well as beta
      catenin, has been found to be a central effector of the growth promoting wingless
      signaling pathway in development. To find out if this pathway is involved in the
      pathogenesis of sporadic HBs, we examined 52 biopsies and three cell lines from
      sporadic HBs for mutations in the APC and beta-catenin genes. Using single-strand
      conformational polymorphism analysis, deletion screening by PCR, and direct
      sequencing, we found a high frequency of beta-catenin mutations in sporadic HBs
      (48%). The mutations affected exon 3 encoding the degradation targeting box of
      beta-catenin leading to accumulation of intracytoplasmic and nuclear beta-catenin
      protein. The high frequency of activating mutations in the beta-catenin gene
      indicates an important role in the pathogenesis of HB.

PMID- 9927030
TI  - Perivascular cells harboring multiple endocrine neoplasia type 1 alterations are
      neoplastic cells in angiofibromas.
AB  - Although neoplasia is caused by clonal proliferation of cells, the resulting
      tumors are frequently heterogeneous, being composed of both neoplastic and
      reactive cells. Therefore, identification of tumors as neoplastic processes is
      frequently obscured. We studied cutaneous angiofibroma, which is a tumor of
      unknown etiology. Combined analysis using immunohistochemistry, selective tissue
      microdissection, fluorescence in situ hybridization, sequencing analysis, and
      deletion analysis of the multiple endocrine neoplasia type 1 locus succeeded in
      the identification of a population of genetically altered, neoplastic cells in
      these tumors. This approach may be valuable in the future in identifying the
      etiology of other tumors of unknown etiology.

PMID- 9927031
TI  - Activation of mitogen-activated protein kinase associated with prostate cancer
      progression.
AB  - Using an antibody specific for dually phosphorylated extracellular-regulated
      kinases 1 and 2, we have examined 82 primary and metastatic prostate tumor
      specimens for the presence of activated mitogen-activated protein (MAP) kinase.
      Nonneoplastic prostate tissue showed little or no staining with activated MAP
      kinase antiserum. In prostate tumors, the level of activated MAP kinase increased
      with increasing Gleason score and tumor stage. In a separate analysis, tumor
      samples from two patients showed no activation of MAP kinase before androgen
      ablation therapy; however, following androgen ablation treatment, high levels of
      activated MAP kinase were detected in the recurrent tumors. Collectively, these
      data suggest an increase in the activation of the MAP kinase signal transduction
      pathway as prostate cancer progresses to a more advanced and androgen-independent
      disease.

PMID- 9927032
TI  - The multilayered organization of engineered human skin does not influence the
      formation of sunlight-induced cyclobutane pyrimidine dimers in cellular DNA.
AB  - Solar UVB initiates skin cancer mainly by generating highly premutagenic
      cyclobutane pyrimidine dimers (CPDs) and subsequent mutations in critical growth
      control genes. It is universally presumed that the upper epidermis in human skin
      blocks a significant portion of the incident UVB, thereby protecting the cancer
      prone basal layer from CPD formation. Using two sensitive techniques for
      measuring CPD in cellular DNA, we confirmed that the multilayered organization of
      engineered human skin efficiently shields the basal layer against 254-nm UVC
      (which is not present in terrestrial sunlight) but, very unexpectedly, provides
      virtually no protection against environmentally relevant UVB. This underscores
      the importance of regular sunscreen use, which, in light of our data, may
      constitute a considerably more important first line of defense against
      photocarcinogenesis than previously believed.

PMID- 9927033
TI  - Human MLH1 deficiency predisposes to hematological malignancy and
      neurofibromatosis type 1.
AB  - Heterozygous germ-line mutations in the DNA mismatch repair genes lead to
      hereditary nonpolyposis colorectal cancer. The disease susceptibility of
      individuals who constitutionally lack both wild-type alleles is unknown. We have
      identified three offspring in a hereditary nonpolyposis colorectal cancer family
      who developed hematological malignancy at a very early age, and at least two of
      them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and
      allele-specific amplification in two siblings revealed a homozygous MLH1 mutation
      (C676T-->Arg226Stop). Thus, a homozygous germ-line MLH1 mutation and consequent
      mismatch repair deficiency results in a mutator phenotype characterized by
      leukemia and/or lymphoma associated with neurofibromatosis type 1.

PMID- 9927034
TI  - Neurofibromatosis and early onset of cancers in hMLH1-deficient children.
AB  - Hereditary nonpolyposis colon cancer is a common hereditary disorder caused by
      the germ-line mutations of DNA mismatch repair (MMR) genes, especially hMLH1 and
      hMSH2. We report here the first identification of human compounds with a
      homozygous inactivation of a MMR gene. In a typical hereditary nonpolyposis colon
      cancer family, MMR-deficient children conceived from matings between
      heterozygotes for a hMLH1 deleterious mutation exhibited clinical features of de
      novo neurofibromatosis type I and early onset of extracolonic cancers. This
      observation demonstrates that MMR deficiency is compatible with human development
      but may lead to mutations during embryogenesis. On the basis of clinical symptoms
      observed in MMR-deficient children, we speculate that the neurofibromatosis type
      1 gene is a preferential target for such alterations.

PMID- 9927035
TI  - Asbestos and DNA double strand breaks.
AB  - A radiosensitive DNA repair-deficient xrs-5 cell line was used to study asbestos
      cytotoxicity and DNA double strand breaks (DSBs). Although xrs-5 cells did not
      show any increase in sensitivity to chrysotile fibers in short-term (4-h)
      treatment when compared with wild-type CHO cells, longer-term exposure (24 h)
      gave significantly lower cell survival accompanied by a cell growth delay as well
      as a higher DNA DSB induction in this mutant cell line. These results suggest an
      important role played by DNA DSBs at the initial stage of asbestos injury.

PMID- 9927036
TI  - A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T
      cells with enhanced functional characteristics: implication for more effective
      immunotherapy.
AB  - In the present study, we show that a singly substituted peptide derived from the
      epitope MART1(27-35) and containing a Leu in position 1 (LAGIGILTV; 1L) behaves
      as a superagonist by in vitro inducing specific T cells with enhanced
      immunological functions. 1L-specific CTLs can be raised from peripheral blood of
      HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate
      peptide. These T cells show a greater sensitivity to native MART1(27-35) when
      compared with CTL variable raised to parental peptide from the same patients.
      More importantly, anti-1L but not anti-native T cells display high levels of
      interferon gamma production at early time points, and readily secreted
      interleukin-2 in response to native epitope endogenously presented by melanoma
      cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of
      MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised
      to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests
      that the native and 1L peptides stimulate different components of the MART1(27
      35)-reactive T cell population. These data provide rationale to the use of
      superagonist analogues of tumor antigens for inducing in vivo immunization
      potentially able to overcome tumor immune escape and mediate a more significant
      control of tumor growth.

PMID- 9927037
TI  - Somatic mutations in the kinase domain of the Met/hepatocyte growth factor
      receptor gene in childhood hepatocellular carcinomas.
AB  - The MET protooncogene encodes a transmembrane tyrosine kinase identified as the
      receptor of a polypeptide known as hepatocyte growth factor/scatter factor. We
      performed PCR-based single-strand conformational polymorphism and sequencing
      analysis of the tyrosine kinase domain of the MET gene (exon 15-19) in 75 primary
      liver cancers. Three missense mutations were detected exclusively in 10 childhood
      hepatocellular carcinomas (HCCs), while no mutations were detected in 16 adult
      HCCs, 21 cholangiocarcinomas, or 28 hepatoblastomas. The extremely short
      incubation period from hepatitis B virus infection to the genesis of childhood
      HCC as compared with the adult HCC suggests that there may be an additional
      mechanism that accelerates the carcinogenesis of childhood HCC. Our results
      indicate that mutations of the tyrosine kinase domain of the MET gene may be
      involved in the acceleration of the carcinogenesis in childhood HCC.

PMID- 9927038
TI  - Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors.
AB  - Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently
      have deletions of chromosome 1, suggesting that inactivation of a tumor
      suppressor gene from chromosome 1 is important in their tumorigenesis. We
      hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine
      tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were
      studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite
      markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied.
      Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8)
      than tumors without metastases (3 of 21) (P = 0.004). Tumors in patients with
      lymph node involvement and patients with multiple endocrine neoplasia type 1 did
      not demonstrate LOH for chromosome 1 markers. These data suggest that loss of
      chromosome 1 is associated specifically with the development of hepatic
      metastases in patients with sporadic pancreatic endocrine tumors.

PMID- 9927039
TI  - Glioblastoma cell-specific expression of fibroblast growth factor receptor-1beta
      requires an intronic repressor of RNA splicing.
AB  - The fibroblast growth factor receptor-1 (FGFR-1) primary transcript is
      alternatively processed to produce receptors that vary in their ligand affinity
      and specificity. A high affinity form of this receptor--FGFR-1beta--that lacks
      the alpha exon is observed on the neoplastic transformation of glial cells. In
      this study, we have identified a 62-bp sequence located 97 bp downstream from the
      alpha exon that is required for the exclusion of this exon in a human
      glioblastoma cell line. Deletion or mutation of this sequence is sufficient to
      allow enhanced inclusion of the alpha exon or a heterologous exon in glioblastoma
      cells. Therefore, it would appear that this sequence element plays a key role in
      the glioblastoma-specific splicing to form FGFR-1beta mRNA.

PMID- 9927040
TI  - Mutational inactivation of transforming growth factor beta receptor type II in
      microsatellite stable colon cancers.
AB  - We previously demonstrated that mutational inactivation of transforming growth
      factor beta type II receptors (RIIs) is very common among the 13% of human colon
      cancers with microsatellite instability. These mutations principally cluster in
      the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon
      cancers, we now find that non-BAT-RII point mutations inactivate RII in another
      15% of cases, thus doubling the known number of colon cancers in which RII
      mutations are pathogenetic. Functional analysis confirms that these mutations
      inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate
      a transforming growth factor beta signaling blockade distal to RII. The
      transforming growth factor beta pathway and RII in particular are major targets
      for inactivation in MSS colon cancers as well as in colon cancers with
      microsatellite instability.

PMID- 9927041
TI  - Loss of adenoviral receptor expression in human bladder cancer cells: a potential
      impact on the efficacy of gene therapy.
AB  - There is great interest in the development of gene therapeutic strategies for the
      treatment of benign and malignant diseases. Recombinant adenovirus has a wide
      spectrum of tissue specificity and is an efficient vector delivery system.
      Successful gene delivery, however, requires viral entry into the target cells via
      specific receptor-mediated uptake. Recently, a cDNA clone (the coxsackie and
      adenovirus receptor [CAR]) encoding a 46-kDa protein was identified as the
      receptor for group C adenovirus (e.g., adenovirus type 2 and 5). Currently,
      little is known regarding the expression of adenoviral receptor in normal tissue
      and cancer. In this paper, we have documented a significant difference in viral
      receptor levels that may be due to transcriptional regulation of the CAR gene in
      several human bladder cancer cell lines. The differences in viral receptor levels
      in these cells correlated with their sensitivity to viral infection. Transfection
      of receptor-negative cell line with CAR cDNA led to increased virus binding and
      increased susceptibility to adenovirus-mediated gene delivery. Our results
      demonstrate that the expression of adenoviral receptor is variable among human
      bladder cancer cells. This variability may have a significant impact on the
      outcome of adenovirus-based gene therapy.

PMID- 9927042
TI  - Photodynamic therapy sensitivity is not altered in human tumor cells after
      abrogation of p53 function.
AB  - Photodynamic therapy (PDT) is an effective local cancer treatment that induces
      cytotoxicity through the intracellular generation of reactive oxygen species. The
      current study investigated whether abrogation of wild-type p53 expression
      modified the sensitivity of tumor cells to PDT-mediated oxidative stress. In
      these experiments, human colon (LS513) and breast (MCF-7) carcinoma cells
      exhibiting a wild-type p53 phenotype were directly compared to LS513 and MCF-7
      cells with abrogated p53 function induced by stable integration of the human
      papillomavirus type 16 E6 viral oncoprotein. The effectiveness of this viral
      oncoprotein to target p53 for degradation was confirmed using a p53
      transactivation reporter gene assay. Western analysis also confirmed attenuated
      expression of p53 in E6-transfected cells. Photosensitivity of PDT-treated cells
      was measured by a clonogenic assay and found to be equivalent for parental and
      p53-abrogated cells. PDT-mediated oxidative stress resulted in a rapid shift of
      pRb from a hyperphosphorylated form to a predominantly underphosphorylated form
      in parental cells that was not preceded by increases in p53 or p21 expression.
      Hypophosphorylated pRb was also observed in PDT-treated LS513/E6 and MCF-7/E6
      cells, further indicating that p53 was not involved in this process. Delayed
      expression of p53 and p21 proteins was seen in parental cells 24-48 h after
      photosensitization. Cell cycle analysis showed that the abrogation of p53 had
      minimal effects on an observed PDT-induced G1 block. Rapid induction of apoptosis
      was documented in PDT-treated LS513 cells, whereas LS513/E6 treated cells
      exhibited reduced apoptosis in response to PDT. The MCF-7 cell lines exhibited a
      minimal apoptotic response to PDT. These results indicate that p53 expression
      does not directly modulate tumor cell sensitivity to PDT in either apoptosis
      responsive (LS513) or nonresponsive (MCF-7) cells.

PMID- 9927044
TI  - Transcription factor Y-box binding protein 1 binds preferentially to cisplatin
      modified DNA and interacts with proliferating cell nuclear antigen.
AB  - The Y-box binding protein (YB-1) binds to inverted CCAAT box sequences that are
      present in the promoter region of many genes. We previously showed that YB-1 is
      overexpressed in human cancer cell lines that are resistant to cisplatin and that
      the depletion of YB-1 by transfection of a vector expressing YB-1 antisense RNA
      increases the sensitivity of human cancer cells to cisplatin. To determine
      whether YB-1 can bind to cisplatin-modified DNA, we fused YB-1 cDNA to
      glutathione S-transferase (GST) cDNA and purified the resulting GST fusion
      protein. When we tested the fusion protein with unmodified or cisplatin-modified
      oligonucleotides, we found that GST-YB-1 bound more strongly to cisplatin
      modified oligonucleotides, as did GST fusion proteins of high mobility group 1
      (HMG1), HMG2, and xeroderma pigmentosum group A protein. When we assayed the
      ability of proliferating cell nuclear antigen (PCNA) to interact with the GST
      fusion proteins, we observed binding to YB-1 but not to HMG1, HMG2, or xeroderma
      pigmentosum group A. Subsequent experiments demonstrated that YB-1 and PCNA
      interact directly via the COOH-terminal region of YB-1. Using immunochemical
      coprecipitation methods, we observed binding of YB-1 and PCNA in vivo. These
      results suggest that YB-1 can function as a recognition protein for cisplatin
      damaged DNA and that it may be important in DNA repair or in directing the
      cellular response to DNA damage.

PMID- 9927043
TI  - A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic
      acid, with potent differentiating, antiproliferative, and anti-inflammatory
      activity.
AB  - The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic
      acid (CDDO) is a potent, multifunctional molecule. It induces monocytic
      differentiation of human myeloid leukemia cells and adipogenic differentiation of
      mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12
      pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation
      of many human tumor cell lines, including those derived from estrogen receptor
      positive and -negative breast carcinomas, myeloid leukemias, and several
      carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of
      various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor
      necrosis factor-alpha, to induce de novo formation of the enzymes inducible
      nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse
      peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO
      will also protect rat brain hippocampal neurons from cell death induced by beta
      amyloid. The above activities have been found at concentrations ranging from 10(
      6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further
      study in vivo, for either chemoprevention or chemotherapy of malignancy as well
      as for neuroprotection.

PMID- 9927045
TI  - Increased binding affinity and valence of recombinant antibody fragments lead to
      improved targeting of tumoral angiogenesis.
AB  - The formation of new blood vessels (angiogenesis) is an important step in tumor
      progression. Molecules capable of selectively targeting markers of angiogenesis
      may offer opportunities for the in vivo imaging of aggressive tumors and for the
      delivery of toxic agents to the tumoral vasculature. Using antibody phage display
      libraries and combinatorial mutagenesis, we isolated single-chain Fv antibody
      fragments, which recognize with different affinities the same epitope of the ED-B
      domain of fibronectin, a marker of angiogenesis. Two single-chain Fv fragments,
      E1 and L19, with dissociation constants of 41 nM and 0.054 nM, respectively, were
      investigated for their ability to target F9 murine teratocarcinoma grafted s.c.
      in nude mice when injected i.v. in either monomeric or homodimeric form (Mr
      27,000 and 54,000, respectively). Biodistribution studies, performed at two time
      points (4 h and 24 h) with radiolabeled samples, showed that the higher affinity
      antibody targets the tumor significantly better than the lower affinity one, in
      terms both of tumor:organ ratios and of the amounts of antibody delivered to the
      tumor. In particular, more than 20% of the injected dose of dimeric L19
      accumulated per gram of tumor at 4 h; the tumor:organ ratios at 4 h and 24 h were
      in the (2.1-8.6):1 and (10.3-29.4):1 range, respectively. This study demonstrates
      that, although vasculature represents only a small fraction of the total tumor
      mass, anti-ED-B antibodies can selectively target tumors in vivo and that this
      process is particularly efficient if very high-affinity binders are used.

PMID- 9927046
TI  - Genotype-phenotype correlation in murine Apc mutation: differences in enterocyte
      migration and response to sulindac.
AB  - The adenomatous polyposis coli (APC) gene product mediates coordinated cell
      growth in the intestinal mucosa. In humans, germ-line mutations of APC are
      associated with colorectal carcinogenesis, a process that varies in severity
      depending on the length of the protein resulting from the mutant allele. In a
      previous study of the C57BL/6J-Min/+ (Min/+) mouse, we found that the protein
      fragment resulting from truncation at codon 850 of murine Apc was associated with
      changes in enterocyte migration, proliferation, apoptosis, and beta-catenin
      expression. This effect was reversed upon treatment of Min/+ mice with the
      chemopreventive drug sulindac sulfide. In this study, we measured enterocyte
      migration in the Apc1638N mouse, an animal with an Apc mutation that yields no
      detectable APC protein. We found no difference in enterocyte migration,
      proliferation, apoptosis, or beta-catenin levels in the Apc1638N mouse when
      compared to wild-type littermates bearing two normal Apc alleles. Furthermore,
      administration of sulindac sulfide to Apc1638N mice did not alter enterocyte
      migration. These observations suggest that a dominant negative effect altering
      cell migration is exerted by the truncated APC protein present in the Min/+
      mouse. These data also suggest that the effectiveness of chemopreventive agents
      in preventing Apc-related tumor formation may depend on which type of mutation is
      present.

PMID- 9927048
TI  - Interleukin 8: an autocrine growth factor for malignant mesothelioma.
AB  - Interleukin 8 (IL-8) is a potent chemokine that also has a direct growth
      potentiating effect on certain tumors. In the present study, we determined IL-8
      levels in human malignant mesothelioma (MM) effusions and congestive heart
      failure pleural fluids. We also investigated antigenic IL-8 production by
      different MM cell lines, and we describe the role of IL-8 in the autocrine growth
      regulation of MMs. Mesothelial (CRL-9444 = MC) and MM (CRL-2081 = MM-1, CRL-5915
      = MM-2, and CRL-5820 = MM-3) cell lines were grown using standard culture
      methods. The bioactive IL-8 levels were measured in supernatants of cultured
      cells by ELISA, and the expression of cell-associated immunoreactive IL-8 was
      observed by immunohistochemistry. The proliferative activity was determined by
      thymidine ([3H]thymidine) incorporation and also by direct cell counts after
      incubation with varying concentrations of IL-8 in the presence/absence of
      specific polyclonal IL-8 antibody. We found significantly higher levels of IL-8
      in mesothelioma pleural fluids than congestive heart failure and a time-dependent
      increase in IL-8 levels in MM-1 and MM-2 cell supernatants during 96 h of
      incubation. IL-8 levels were nearly undetectable in MM-3 and MC cell line
      supernatants. In MM-1 and MM-2 cells, IL-8 caused a dose-dependent increase of
      [3H]thymidine incorporation to maximal levels of 46.3 +/- 3.6% and 12.3 +/- 1.6%
      (P < 0.001), respectively, when compared with serum-free medium as control.
      Neutralization of IL-8 significantly decreased proliferative activity of MM-1 and
      MM-2. IL-8 did not induce proliferative activity in MM-3 and MC cells. We
      conclude that IL-8 had a direct growth-potentiating activity in MMs.

PMID- 9927047
TI  - Expression of 15-lipoxygenase-1 in human colorectal cancer.
AB  - Recently, we reported the induction of reticulocyte type 15-lipoxygenase (15-Lox
      1) in a human colorectal carcinoma cell line that had been stimulated by butyrate
      to undergo apoptosis and cell differentiation (H. Kamitani et al., J. Biol.
      Chem., 273: 21569-21577, 1998). To determine if 15-Lox-1 is expressed in human
      colorectal cancer tissue, 21 matched pairs of colorectal tumor and adjacent
      normal tissue were examined by immunoblot analysis using specific antibodies for
      human 15-Lox-1, prostaglandin H synthase (also called cyclooxygenase, Cox)-1 and
      Cox-2. Eighteen of the 21 were found to have 15-Lox-1 in both tumor tissue and
      matched adjacent normal tissue, with the 15-Lox-1 expression being significantly
      higher in most of the tumor tissue. The expression of Cox-2 was also elevated in
      most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor
      tissue than in the paired normal tissue. Reverse-phase high-performance liquid
      chromatography analysis of arachidonate metabolites, formed on incubation of
      arachidonic acid with a crude enzyme preparation from the colon samples, revealed
      the formation of 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid with a much lower
      level of 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (15-hydroxy-5Z,8Z,11Z,13E
      eicosatetraenoic acid:12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, 6.5:1)
      which also indicate the presence of 15-Lox-1. Furthermore, reverse transcription
      PCR with primers specific for human 15-Lox-1 or 15-Lox-2 cDNA indicated that 15
      Lox-1 mRNA was present in the colorectal tumors. The sequence of the PCR product
      was identical to the human 15-Lox-1. Immunohistochemical studies showed 15-Lox-1
      localization in the glandular epithelium of human colorectal tumor tissue. These
      results suggest that 15-Lox-1 is highly expressed in human colorectal cancer
      epithelial cells and that its expression may have a role in colorectal
      carcinogenesis.

PMID- 9927049
TI  - The pure antiestrogen ICI 182,780 inhibits progestin-induced transcription.
AB  - The pure antiestrogen ICI 182,780 binds to the estrogen receptor with high
      affinity and is currently in clinical trials for the treatment of human breast
      cancer. We now show for the first time that ICI 182,780 also exhibits potent
      antiprogestin activity at doses frequently used in laboratory investigations. The
      antiprogestin activity of ICI 182,780 was detected in HeLa, HepG2, and CV1 cells
      transiently transfected with either the A or B forms of the human progesterone
      receptor and a luciferase construct driven by a progesterone-response element.
      ICI 182,780 inhibited progesterone-induced gene transcription in a dose-dependent
      fashion with maximum inhibition obtained at 10(-6) M and an IC50 of approximately
      2 x 10(-7) M. The ICI compound produced the same degree of inhibition as that
      obtained with the antiprogestin RU-486. The antiestrogen tamoxifen did not
      display antiprogestin activity in this test system, and ICI 182,780 did not
      inhibit the activity of transfected androgen or glucocorticoid receptors. These
      results clearly establish that ICI 182,780 has significant antiprogestin activity
      in addition to its well-documented antiestrogenic activity and raises the
      possibility that both antihormonal properties of this compound are exhibited in
      laboratory studies and in the course of treatment of human breast tumors.

PMID- 9927050
TI  - Steroid sulfatase expression is an independent predictor of recurrence in human
      breast cancer.
AB  - Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone
      sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present
      study, we have measured STS mRNA levels in 97 breast cancers by reverse
      transcription-PCR using a fluorescent primer in the presence of an internal
      standard RNA and evaluated its association with disease-free and overall
      survival. The median value was 728.0 amol/ng RNA (range, 0-11,778 amol/ng RNA).
      Levels were significantly higher in tumors demonstrating lymph node metastasis
      than in those without nodal involvement (P = 0.033) and in patients who
      experienced a recurrence during the follow-up period (mean, 40.8 months; median,
      39 months) compared with those with no evidence of further disease (mean, 49.2
      months; median, 48 months; P = 0.029). No significant associations were found
      between STS mRNA expression and age, menopausal status, tumor size, histological
      grade, estrogen receptor status, or postoperative adjuvant therapy. High levels
      of STS mRNA proved to be a significant predictor of reduced relapse-free survival
      as a continuous variable (log STS mRNA; P = 0.028). As a dichotomous variable
      with an optimized cutoff point of 1,240 amol/ng RNA, expression was also
      associated with a significantly shorter relapse-free survival rate (P = 0.002),
      but no significant correlation was found between the STS mRNA level and overall
      survival. Expression was found to be an independent factor for predicting relapse
      free survival on multivariate analysis. The results thus support a putative role
      of STS in breast cancer growth and metastasis.

PMID- 9927051
TI  - Signaling pathway activated during apoptosis of the prostate cancer cell line
      LNCaP: overexpression of caspase-7 as a new gene therapy strategy for prostate
      cancer.
AB  - We studied the molecular mechanisms of apoptosis in the prostate cancer cell line
      LNCaP and whether overexpression of caspase activity could force this cell line
      to undergo apoptosis. The inhibitor of phosphomevalonate decarboxylase, sodium
      phenylacetate, and the protein kinase inhibitor staurosporine induced (a) release
      of cytochrome c from the mitochondria to the cytosol; (b) reduction in
      mitochondrial transmembrane potential; (c) proteolytic processing of caspase-3
      and -7 but not -2; (d) cleavage of the DEVD substrate and the death substrates
      poly(ADP-ribose) polymerase and DNA fragmentation factor; and (e) apoptosis. The
      panspecific inhibitor of caspase activation N-benzyloxycarbonyl-Val-Ala-Asp(OMe)
      fluoromethylketone (z-VAD-FMK) prevented all of these events except release of
      mitochondrial cytochrome c into the cytosol. None of these apoptotic signaling
      events were elicited by staurosporine or sodium phenylacetate treatment of LNCaP
      Bcl-2 cells that overexpress the oncoprotein Bcl-2. Because caspase-7 is
      activated in every model of apoptosis that we have characterized thus far, we
      wished to learn whether overexpression of this protease could directly cause
      apoptosis of LNCaP cells. By using a replication-defective adenovirus,
      overexpression of caspase-7 protein in both LNCaP and LNCaP-Bcl-2 cells was
      accompanied by induction of cleavage of the DEVD substrate and TUNEL. These
      studies have demonstrated that caspase-7 and -3 are critical mediators of
      apoptosis in LNCaP cells. Caspase-7 was proteolytically activated in every model
      of apoptosis that we have developed, and the overexpression of it induced
      apoptosis of LNCaP and LNCaP-Bcl-2 cells. Thus, adenoviral-mediated transfer of
      caspase-7 may offer a new effective approach for the treatment of prostate
      cancer.

PMID- 9927053
TI  - Histone deacetylase inhibitors as potential anti-skin cancer agents.
AB  - The regulation of squamous differentiation is a tightly regulated process
      involving transcriptional repression and activation. Previous studies have
      established that squamous carcinoma cell lines inappropriately regulate the
      transcription of genes important to the control of squamous differentiation.
      Histone deactylase inhibitors such as trichostatin A (TSA) and butyrate disrupt
      normal chromatin structure and cause alterations in gene expression/regulation.
      For these reasons, we examined the effects of both butyrate and TSA on the growth
      and differentiation of human keratinocytes or squamous carcinoma cells in tissue
      culture. We found that treatment of keratinocytes or squamous carcinoma cells
      with butyrate induced a reversible growth arrest. TSA, on the other hand, induced
      an irreversible growth arrest in both keratinocytes and squamous carcinoma cells.
      The growth arrest of keratinocytes induced by TSA or butyrate was accompanied by
      a reduction in the mRNA levels for proliferation gene cdk1 and an induction of
      the mRNA for the differentiation-specific transglutaminase type I gene (TG1). In
      contrast, the squamous carcinoma cells had decreased cdk1 and TG1 mRNA in
      response to TSA or butyrate. Both of these agents produced transient increases in
      the acetylation of histone H4 in keratinocytes and squamous carcinoma cells.
      These data indicated that TSA may have potential as a topical treatment for
      epidermal malignancies.

PMID- 9927052
TI  - Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during
      topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation
      dependent pathway.
AB  - Beta-lapachone (beta-Lap) has been found to inhibit DNA topoisomerases (Topos) by
      a mechanism distinct from that of other commonly known Topo inhibitors. Here, we
      demonstrated a pronounced elevation of H2O2 and O2- in human leukemia HL-60 cells
      treated with beta-Lap. Treatment with other Topo poisons, such as camptothecin
      (CPT), Vbeta-16, and GL331, did not have the same effect. On the other hand,
      antioxidant vitamin C (Vit C) treatment effectively antagonized beta-Lap-induced
      apoptosis. This suggested that a reactive oxygen species (ROS)-related pathway
      was involved in beta-Lap-induced apoptosis program. We also found that c-Jun NH2
      terminal kinase (JNK) but not p38 mitogen-activated protein kinase or
      extracellular signal-regulated kinase 1/2 was persistently activated in apoptosis
      induced by beta-Lap. Overexpression of a dominant-negative mutant mitogen
      activated protein kinase kinase kinase 1 (MEKK1-DN) or treatment with JNK
      specific antisense oligonucleotide or Vit C all prevented beta-Lap-induced JNK
      activation and the subsequent apoptosis. Only the expression of MEKK1-DN, not Vit
      C treatment, blocked the JNK activity induced by CPT, Vbeta-16, or GL331. These
      results confirm again that ROS acts as a mediator for JNK activation during beta
      Lap-induced apoptosis. Furthermore, we found that beta-Lap can stimulate
      CPP32/Yama activity, which was, however, markedly inhibited by the MEKK1-DN
      expression or Vit C treatment. Again, CPT-induced CPP32/Yama activation can be
      abolished by MEKK1-DN but not by Vit C treatment. Taken together, these results
      indicate that beta-Lap but not other Topo inhibitors triggers apoptosis
      signaling, i.e., JNK and subsequent CPP32/Yama activation are mediated by the
      generation of ROS.

PMID- 9927055
TI  - Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of
      herpes simplex virus-thymidine kinase.
AB  - A major obstacle to the successful application of suicide gene therapy strategies
      that rely on in situ transduction of tumor cells is the poor distribution of the
      vector throughout the tumor mass. To address this problem, we evaluated the use
      of Ad.TK(RC), an E1b Mr 55,000 deleted replicating adenoviral vector engineered
      to express the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) in
      combination with ganciclovir (GCV) as a treatment for human colon cancer
      xenografts in nude mice. We compared the efficacy of this system with that of a
      standard replication-deficient adenovirus expressing HSV-tk (Ad.TK) in mice
      bearing LS180 tumors. In this system, Ad.TK(RC) alone was as effective as a
      traditional Ad.TK vector in combination with GCV. The addition of GCV
      significantly enhanced the antitumor effect of Ad.TK(RC). Furthermore, we
      demonstrated that the survival of HT-29 human colon cancer xenografted mice
      treated with Ad.TK(RC) and GCV was prolonged compared with Ad.TK(RC) alone or
      with administration of a single cycle of topotecan. These data demonstrate that
      the addition of direct viral oncolysis to the HSV-tk/GCV suicide gene system
      resulted in a striking improvement in treatment efficacy and that it may offer
      advantages over the use of chemotherapeutic agents for treatment of localized
      disease.

PMID- 9927054
TI  - The use of Zn-desferrioxamine for radioprotection in mice, tissue culture, and
      isolated DNA.
AB  - Redox-active metals mediate oxidative injury and might also potentiate radiation
      damage. The iron chelator desferrioxamine (DFO), which diminishes oxidative
      damage in many chemical and biological systems as well as in human subjects, has
      a controversial role in radiobiology and reportedly acts both as a
      radiosensitizer and a radioprotector. The present research focused on the
      radioprotective activity of its zinc complex. Zn-DFO was studied using three test
      systems differing by their complexities: isolated DNA from pUC 19 plasmid,
      cultured V79 Chinese hamster cells, and C3H mice. Zn-DFO (0.5-2 mM) protected
      isolated DNA against gamma-radiation better than each of its components alone;
      however, neither Zn-DFO nor DFO (50-100 microM) alone affected the radiation
      sensitivity of cultured cells. With total body irradiation, Zn-DFO, but not DFO
      alone at 100 micromol/kg body weight, administered to mice 30 min before
      irradiation provided significant radioprotection (P < 0.01). Zn-DFO had an
      LD(50/30) of 10.3 Gy, whereas DFO and vehicle alone had LD(50/30) of 8.03 Gy and
      7.91 Gy, respectively. The effect of Zn-DFO on the hemodynamic parameters in mice
      did not differ from that of the vehicle (saline) alone. This excludes the
      explanation that the radioprotective activity of Zn-DFO results from its effect
      on oxygen levels. In addition to the possible direct effect of Zn, other
      potential modes of action underlying the radioprotective activity of Zn-DFO might
      involve a displacement of iron and its substitution by zinc, a greater proximity
      of the drug to DNA, and less likely an improved penetration of the drug into
      cells because of its structure. The failure of Zn-DFO to protect cells in tissue
      cultures indicates that it has some systemic role in the whole animal, possibly
      due to a prolonged half-life in the animal's circulation.

PMID- 9927056
TI  - Immune events associated with the cure of established tumors and spontaneous
      metastases by local and systemic interleukin 12.
AB  - The antitumor activity of recombinant murine interleukin-12 (rIL-12) is
      documented by a large set of data from numerous mouse models. Because the
      cellular and molecular mechanisms by which rIL-12 impairs tumor growth are still
      not fully defined, we compared the effects of local and systemic rIL-12
      administration in mice harboring an invasive 7-day-old moderately differentiated
      and spontaneously metastasizing mammary adenocarcinoma (TSA). Whereas the immune
      events elicited via the two routes of rIL-12 administration seem to be the same,
      systemic rIL-12 is markedly more effective; tumor destruction is dependent on a
      prompt antitumor response resulting from the cooperation of several subsets of
      reactive cells. The reactions that seem to play a key role are: (a) indirect
      inhibition of angiogenesis by secondary cytokines (mainly IFN-gamma) and third
      level chemokines (inducible protein 10 and monokine induced by IFN-gamma); (b)
      systemic activation of leukocyte subsets capable of producing proinflammatory
      cytokines, CTLs, and antitumor antibodies; and (c) destruction of tumor vessels
      by polymorphonuclear cells. The markedly higher efficacy of systemic rIL-12 seems
      to rest on its ability to recruit these systemic reactions more quickly and
      efficiently than local rIL-12.

PMID- 9927057
TI  - The pharmacokinetic characteristics of glycolated humanized anti-Tac Fabs are
      determined by their isoelectric points.
AB  - To evaluate a method for preventing the nephrotoxicity caused by the high renal
      accumulation of radiolabeled or toxin-conjugated small immunoproteins used for
      cancer therapy, we conjugated humanized anti-Tac Fab fragments with various
      numbers of glycolate molecules [glycolated Fab fragments (glyco-Fabs)] and
      separated the conjugates by means of ion-exchange columns into three fractions,
      depending on their isoelectric points (pIs). We evaluated the biodistribution,
      pharmacokinetics, and catabolism in normal nude mice of nonglycolated Fab (pI >
      or = 9.3) and three different preparations of glyco-Fab, including strongly
      anionic glyco-Fab (sa-glyco-Fab: pI < or = 4.5), mildly anionic glyco-Fab (pI =
      4.5-7), and mildly cationic glyco-Fab (pI = 7-9.3). In addition, the
      biodistributions of 125I-labeled sa-glyco-Fab and 131I-labeled nonglycolated Fab
      were evaluated in normal nude mice coinjected with 50 mg of L-lysine and/or 1
      microg of furosemide and in a control group without coinjection. We then
      evaluated the serial biodistribution of 125I-labeled sa-glyco-Fab (4 microCi/1
      microg) and 131I-labeled nonglycolated Fab (5 microCi/1 microg) in Tac antigen
      positive (ATAC4) and -negative (A431) tumor-bearing nude mice with s.c. tumor
      xenografts derived from Tac antigen-positive ATAC4 cells and receptor-negative
      A431 cells. These animals were coinjected with 30 mg of lysine i.v. and 30 mg of
      lysine i.p. 15 min after the radiolabeled Fab injection. To evaluate the
      biodistribution data and study scintigraphic imaging, we performed serial
      scintigraphy on normal and tumor-bearing mice with all four 131I-labeled
      preparations. 125I-labeled mildly cationic glyco-Fab and 131I-labeled
      nonglycolated Fab had similar distributions, except in the kidney. However, both
      125I-labeled anionic glyco-Fab preparations showed significantly different
      distributions from both cationic Fabs in the blood, liver, lung, and spleen.
      Renal accumulation of all four radiolabeled Fab preparations increased
      significantly as the pI increased (P < 0.01). In addition, the intact fraction of
      Fab excreted into urine increased as pI decreased. Therefore, the glomerular
      filtration depended on whether the charge on the Fab was positive or negative.
      The proportion of Fab reabsorbed by the proximal tubules increased as pI
      increased. 125I-labeled sa-glyco-Fab and 125I-labeled mildly anionic glyco-Fab
      showed a similar distribution in the blood and all organs except the kidney.
      Lysine led to an additional blocking effect on proximal tubular uptake of both sa
      glyco-Fab and nonglycolated Fab. Addition of furosemide yielded only a small
      effect when used with lysine. With lysine, the sa-glyco-Fab:nonglycolated Fab
      estimated integral radioactivity ratios were 4.7 and 0.7 in the ATAC4 tumor and
      in the kidney, respectively. The use of anionic fragments, which may be used in
      conjunction with lysine, represents a promising approach that may help decrease
      the renal toxicity of other small fragments, the molecular weights of which range
      from Mr 40,000 to 70,000, and, thereby, allow higher doses of radiation to the
      tumor.

PMID- 9927058
TI  - Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from
      carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with
      peptide-pulsed dendritic cells.
AB  - The human carcinoembryonic antigen (CEA) and HER-2/neu are potential target
      antigens for CTL specific immunotherapy for common malignancies such as breast,
      lung, colon, and gastric carcinomas. Several CTL epitopes restricted by HLA-A2,
      the most common human histocompatibility molecule, have been previously reported.
      However, to develop CTL-based immunotherapies for the general population, it is
      necessary to identify epitopes restricted by other common histocompatibility
      alleles. Here, we describe two HLA-A3-restricted CTL epitopes from the CEA and
      HER-2/neu antigens. HLA-A3 binding synthetic peptides from CEA and HER-2/neu were
      tested for immunogenicity by in vitro primary CTL induction protocol using
      peripheral blood mononuclear cells from normal healthy volunteers. One peptide
      from CEA (CEA[9(61)]: HLFGYSWYK) and one peptide from HER-2/neu (HER2[9(754)]:
      VLRENTSPK) were shown to induce CTL that was capable of killing a tumor cell line
      expressing HLA-A3 and the corresponding tumor-associated antigen. Additional MHC
      binding studies with the most common HLA molecules belonging to the HLA-A3
      superfamily (HLA-A*1101, -A*3101, -A*3301, and -A*6801), demonstrated that
      CEA[9(61)] binds five of five A3 supertype molecules with high affinity, and the
      HER2[9(754)] epitope was able to bind to four of the same five alleles. These
      results indicate that these two new CTL epitopes should be immunogenic in
      individuals expressing either HLA-A3, or other members of the HLA-A3 superfamily.

PMID- 9927059
TI  - Extensive intra- and interindividual heterogeneity of p15INK4B methylation in
      acute myeloid leukemia.
AB  - Silencing of the cyclin-dependent kinase inhibitor gene p15INK4B by cytosine
      methylation of the promoter region has been associated with some types of
      hematological malignancy. To study in detail the patterns of p15INK4B methylation
      in patients with acute myeloid leukemia, we adopted a novel approach based on PCR
      amplification of bisulfite-treated DNA followed by resolution of differentially
      methylated sequences by denaturing gradient gel electrophoresis. This method
      visually displays the degree and heterogeneity of DNA methylation and enables the
      isolation and characterization of distinct clonotypic epigenotypes. A
      surprisingly high degree of intra- and interindividual heterogeneity of p15INK4B
      methylation was observed in the 65 acute myeloid leukemia patients examined.
      Methylation was detected in 46 (71%) of the patients and was observed more
      frequently in the French-American-British subtypes M1/M2 than in M4/M5 (P <
      0.025). Examination of the same panel of samples using a highly sensitive
      methylation-specific PCR method showed methylated p15INK4B alleles in 61 (94%) of
      the samples. We present evidence that the higher frequency of p15INK4B
      methylation determined by methylation-specific PCR may, at least in part, be due
      to the presence of a small fraction of p15INK4B-methylated lymphocytes in normal
      blood.

PMID- 9927060
TI  - Tumor suppressor PTEN inhibition of cell invasion, migration, and growth:
      differential involvement of focal adhesion kinase and p130Cas.
AB  - PTEN/MMAC1 is a major new tumor suppressor gene that encodes a dual-specificity
      phosphatase with sequence similarity to the cytoskeletal protein tensin.
      Recently, we reported that PTEN dephosphorylates focal adhesion kinase (FAK) and
      inhibits cell migration, spreading, and focal adhesion formation. Here, the
      effects of PTEN on cell invasion, migration, and growth as well as the
      involvement of FAK and p130 Crk-associated substrate (p130Cas) were investigated
      in U87MG glioblastoma cells missing PTEN. Cell invasion, migration, and growth
      were down-regulated by expression of phosphatase-active forms of PTEN but not by
      PTEN with an inactive phosphatase domain; these effects were correlated with
      decreased tyrosine phosphorylation levels of FAK and p130Cas. Overexpression of
      FAK concomitant with PTEN resulted in increased total tyrosine phosphorylation
      levels of FAK and p130Cas and effectively antagonized the effects of PTEN on cell
      invasion and migration and partially on cell growth. Overexpression of p130Cas
      increased total tyrosine phosphorylation levels of p130Cas without affecting
      those of FAK; however, although p130Cas could reverse PTEN inhibition of cell
      invasion and migration, it did not rescue cell growth in U87MG cells. In contrast
      to FAK, p130Cas could not be shown to interact with PTEN in cells, and it was not
      dephosphorylated directly by PTEN in vitro. These results suggest important roles
      of PTEN in the phenotype of tumor progression, and that the effects of PTEN on
      cell invasion, migration, and growth are mediated by distinct downstream pathways
      that diverge at the level of FAK.

PMID- 9927062
TI  - Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to
      the identification of four new deletions.
AB  - Most previous BRCA1 mutation screening studies conducted on breast cancer
      families were aimed at identifying mutations in the coding sequence and splice
      sites. Mutations in the promoter and untranslated regions, and large
      rearrangements are missed by standard mutation detection strategies. To look
      specifically for such germ-line mutations in the BRCA1 gene, we have analyzed a
      series of 27 American and 51 French breast cancer families in which no BRCA1
      mutation was identified by classical techniques. No mutations were detected in
      either the promoter or untranslated regions, and we did not find any deletion of
      the whole gene. Four families were found to carry distinct deletions. Two of
      them, probably generated by Alu-mediated homologous recombination, were internal
      deletions of 3 and 23.8 kb, encompassing exon 15 and exons 8-13, respectively.
      These alterations both lead to a frameshift in the mutant mRNA and to premature
      stop codon-mediated mRNA decay. The other two deletions encompass exons 1 and 2.
      On the basis of previous and present analyses, rearrangements represent 8% (3/37)
      of all mutations in our set of BRCA1 American families. Consequently, the search
      for rearrangements appears mandatory in BRCA1 mutation screening studies.

PMID- 9927061
TI  - Comparative genomic hybridization and loss of heterozygosity analyses identify a
      common region of deletion at 15q11.1-15 in human malignant mesothelioma.
AB  - Comparative genomic hybridization analysis was performed to identify chromosomal
      imbalances in 24 human malignant mesothelioma (MM) cell lines derived from
      untreated primary tumors. Chromosomal losses accounted for the majority of
      genomic imbalances. The most frequent underrepresented segments were 22q (58%)
      and 15q1.1-21 (54%); other recurrent sites of chromosomal loss included 1p12-22
      (42%), 13q12-14 (42%), 14q24-qter (42%), 6q25-qter (38%), and 9p21 (38%). The
      most commonly overrepresented segment was 5p (54%). DNA sequence amplification at
      3p12-13 was observed in two cases. Whereas some of the regions of copy number
      decreases (i.e., segments in 1p, 6q, 9p, and 22q) have previously been shown to
      be common sites of karyotypic and allelic loss in MM, our comparative genomic
      hybridization analyses identified a new recurrent site of chromosomal loss within
      15q in this malignancy. To more precisely map the region of 15q deletion, loss of
      heterozygosity analyses were performed with a panel of polymorphic microsatellite
      markers distributed along 15q, which defined a minimal region of chromosomal loss
      at 15q11.1-15. The identification of frequent losses of a discrete segment in 15q
      suggests that this region harbors a putative tumor suppressor gene whose
      loss/inactivation may contribute to the pathogenesis of many MMs.

PMID- 9927063
TI  - Causes and consequences of microsatellite instability in endometrial carcinoma.
AB  - Genetic instability of microsatellite repeat sequences [microsatellite
      instability (MI)] is commonly seen in tumors associated with the hereditary
      nonpolyposis colorectal cancer syndrome and is a result of inactivating mutations
      in any of several genes involved in a particular pathway of DNA mismatch repair.
      Sporadic (i.e., nonhereditary) manifestations of several tumor types, including
      colorectal, gastric, and endometrial carcinomas, also exhibit MI in a significant
      fraction of cases. Many MI+ sporadic colorectal carcinomas are associated with
      somatic mutations of mismatch repair genes, and several genes with coding region
      microsatellites are frequently mutated as a result in these cancers. The
      molecular causes and consequences of MI in sporadic endometrial carcinomas remain
      obscure, however. The aims of this study were: (a) to identify a series of
      sporadic endometrial carcinomas with clear evidence of MI; (b) to determine the
      extent to which somatic alterations in mismatch repair genes are associated with
      this MI; and (c) to establish whether the genes containing coding region
      microsatellite repeats that are known to be disrupted in MI+ gastrointestinal
      cancers are also disrupted in MI+ endometrial carcinomas. Matched pairs of normal
      and tumor DNA from 57 consecutive cases of endometrial carcinoma were examined
      for evidence of MI using a consensus panel of microsatellite markers. Fourteen
      cases (25%) displayed unequivocal evidence of MI, consistent with previously
      published estimates of the incidence of MI+ sporadic endometrial carcinoma. These
      cases were subjected to a mutation screen of the coding regions and exon-intron
      boundaries of the mismatch repair genes MSH2 and MLH1. Although several
      polymorphisms were detected, no clearly deleterious mutations were found in
      either of these genes. Notably, however, hypermethylation of the MLH1 promoter
      region was identified in 10 of 14 (71%) MI+ cases. Somatic mutations in coding
      region microsatellite repeats in the TGFbetaIIR, IGFIIR, BAX, E2F4, MSH3, MSH6,
      BRCA1, and BRCA2 genes were generally rare. Four MI+ tumors (29%) contained
      somatic mutations in the PTEN gene, only one of which was likely the result of
      MI. These data indicate that somatic mutational inactivation of known mismatch
      repair genes does not account for the great majority of sporadic endometrial
      carcinomas with MI and that a significant fraction of these cases may instead be
      causally associated with hypermethylation of the MLH1 promoter. Furthermore,
      genes with coding region microsatellites that are frequently mutated in MI+
      gastrointestinal cancers are rarely mutated in MI+ endometrial cancers, implying
      the existence of alternative molecular targets for the tumorigenic effects of MI
      in this tumor type.

PMID- 9927064
TI  - Enhanced production and activation of progelatinase A mediated by membrane-type 1
      matrix metalloproteinase in human papillary thyroid carcinomas.
AB  - Matrix metalloproteinases (MMPs) are believed to be involved in the invasion and
      metastasis of various human carcinomas. In the present study, the production
      levels of seven different MMPs (MMP-1, -2, -3, -7, -8, -9, and -13), the
      activation of the zymogen of MMP-2 (proMMP-2), the expression of membrane-type
      MMPs (MT1-, MT2-, and MT3-MMPs), and the tissue localization of the activated
      enzyme were examined in human invasive papillary thyroid carcinomas. Sandwich
      enzyme immunoassays revealed that among the MMPs examined, only the MMP-2
      production level is significantly enhanced in the carcinoma tissues compared with
      the follicular adenoma and normal control thyroid tissues. Gelatin zymography
      indicated that the proMMP-2 activation ratio is considerably higher in carcinomas
      with lymph node metastasis than it is in those without metastasis, follicular
      adenomas, or normal controls (P < 0.01). Northern blot analysis of the expression
      of MT1-, MT2-, and MT3-MMPs, which are known to activate proMMP-2 in vitro,
      demonstrated the predominant expression of MT1-MMP mRNA in the carcinoma tissues
      (15 of 15 cases), whereas MT2-MMP expression was confined to 26% of the cases (4
      of 15 cases), and no consistent expression of MT3-MMP was observed. MTI-MMP mRNA
      expression levels correlated with the proMMP-2 activation ratio (r = 0.692; P <
      0.01), but such a correlation was not obtained with MT2-MMP. There was also a
      direct correlation between MT1-MMP expression and lymph node metastasis (P <
      0.05). In situ hybridization indicated that both carcinoma and stromal cells
      express MT1-MMP transcripts (five of six cases). MT1-MMP was also immunolocalized
      to carcinoma and stromal cells in all of the carcinoma samples (26 of 26 cases),
      which were positive for MMP-2. In situ zymography indicated definite
      gelatinolytic activity in the carcinoma cell nests, which was abolished by
      incubation of the carcinoma samples with a synthetic MMP inhibitor before the
      reaction. These results suggest for the first time that among seven different
      MMPs, the production of proMMP-2 and its MT1-MMP-mediated activation in the
      carcinoma cell nests play an important role in the lymph node metastasis of human
      invasive papillary thyroid carcinomas.

PMID- 9927065
TI  - 12-O-tetradecanoylphorbol-13-acetate induces clonal expansion of potentially
      malignant keratinocytes in a tissue model of early neoplastic progression.
AB  - Tumor promoters stimulate the selective expansion of initiated mouse
      keratinocytes in the two-stage model of skin carcinogenesis. However, it is not
      clear whether these promoters directly modulate the growth of initiated cells or
      rather permit clonal expansion of initiated cells by modifying the environment of
      adjacent normal cells. The goal of this study was to further understand the
      mechanism of action of tumor promotion during early neoplastic progression of
      human stratified epithelium. To accomplish this, we have established an
      organotypic culture model that mimics a preneoplastic tissue and contains
      mixtures of genetically marked (beta-galactosidase), low-grade malignant
      keratinocytes (HaCaT-ras II-4) and normal human keratinocytes (NHKs) to monitor
      the fate and phenotype of these cells after treatment with 12-O
      tetradecanoylphorbol-13-acetate (TPA). In submerged culture, concentrations of
      0.001-1 microg/ml TPA were shown to limit the growth of NHKs yet had no effect on
      growth of II-4 cells. TPA (0.001 microg/ml) was then added to organotypic
      cultures containing mixtures of NHK:II-4 cells at varying ratios to determine
      whether this agent could selectively stimulate clonal expansion of II-4 cells in
      a normal epidermal background. Immunofluorescence for beta-galactosidase
      demonstrated that TPA caused a significant increase in the percentage of beta
      galactosidase-positive areas in 12:1 and 4:1 mixtures. This TPA-induced expansion
      of II-4 cells was associated with a marked decrease in proliferation of NHKs,
      suggesting that II-4 could selectively expand because of its growth advantage
      relative to NHKs. Clonal expansion of tumor cells was temporally linked to the
      decreased expression of filaggrin and keratin 1 expression in adjacent NHKs.
      These findings indicate that TPA may enable expansion of potentially malignant
      cells through the epigenetic modification of proliferation in NHKs and
      differentiation of NHK and II-4 cells.

PMID- 9927067
TI  - Angiogenesis and cancer: AACR special conference in cancer research. American
      Association for Cancer Research.

PMID- 9927066
TI  - Mannosylerythritol lipid is a potent inducer of apoptosis and differentiation of
      mouse melanoma cells in culture.
AB  - Malignant melanomas are tumors that are well known to respond poorly to treatment
      with chemotherapeutic reagents. We report here that mannosylerythritol lipid
      (MEL), an extracellular glycolipid from yeast, markedly inhibited the growth of
      mouse melanoma B16 cells in a dose-dependent manner. Exposure of B16 cells to MEL
      at 10 microM and higher concentrations caused the condensation of chromatin, DNA
      fragmentation, and sub-G1 arrest, all of which are hallmarks of cells that are
      undergoing apoptosis. Analysis of the cell cycle also suggested that both the MEL
      mediated inhibition of growth and apoptosis were closely associated with growth
      arrest in the G1 phase. Moreover, MEL exposure stimulated the expression of
      differentiation markers of melanoma cells, such as tyrosinase activity and the
      enhanced production of melanin, which is an indication that MEL triggered both
      apoptotic and cell differentiation programs. Forced expression of Bcl-2 protein
      in stably transformed B16 cells had a dual effect: it interfered with MEL-induced
      apoptosis but increased both tyrosinase activity and the production of melanin as
      compared with these phenomena in vector-transfected MEL-treated control B16
      cells. These results provide the first evidence that growth arrest, apoptosis,
      and the differentiation of mouse malignant melanoma cells can be induced by a
      microbial extracellular glycolipid.

PMID- 9927068
TI  - Ninth annual Pezcoller Symposium: The biology of tumors.

PMID- 9927069
TI  - Innovative approaches to the prevention, diagnosis, and therapy of cancer: fourth
      joint conference of the American Association for Cancer Research (AACR) and the
      Japan Cancer Association (JCA).

PMID- 9927070
TI  - Severe hemorrhage after implant surgery.

PMID- 9927071
TI  - Impacted lower third molar and the inferior alveolar nerve.

PMID- 9927072
TI  - Latex allergy: a review for the dental professional.
AB  - Reactions to latex products are reportedly occurring with an increased frequency
      both in patients and in health care providers. Natural rubber latex is found in
      numerous products, and adverse latex reactions range from contact dermatitis to
      life-threatening anaphylaxis. A complete understanding of the pathophysiology of
      latex allergy provides the foundation for the proper diagnosis and treatment of
      patients with latex allergy. This article provides the reader with a review of
      latex allergy and suggests strategies for the management of patients with latex
      hypersensitivity.

PMID- 9927073
TI  - Inflammatory bowel diseases and the oral cavity.

PMID- 9927074
TI  - Prevalence of temporomandibular joint disk displacement in infants and young
      children.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of
      temporomandibular joint disk displacement in infants and young children. STUDY
      DESIGN: Magnetic resonance images were obtained of the temporomandibular joints
      in 30 infants and young children ranging in age from 2 months to 5 years (median
      age, 3 years; mean age, 2.5 years). RESULTS: All joints had normal superior disk
      position. The computed 95% confidence interval was 0.00-0.06, which implies a
      minimal probability that disk displacement would occur in this age group.
      CONCLUSIONS: The result contradicts previous suggestions that temporomandibular
      joint disk displacement could represent a congenital normal anatomic variant.

PMID- 9927076
TI  - Prevalence of dental trauma in 6000 patients with facial injuries: implications
      for prevention.
AB  - OBJECTIVE: In contrast to epidemiologic studies on facial injuries reporting on
      dental trauma, facial bone fractures with dentoalveolar injuries, or soft tissue
      injuries individually, the purpose of this study was to evaluate the overall
      place of dental trauma in facial injuries. This was a retrospective investigation
      of the impact of sport, work, violence, traffic, household, and play accidents in
      the relationships among dental trauma, facial trauma, and other concomitant
      trauma. Finally, preventive considerations are discussed. STUDY DESIGN: Six
      thousand patients registered at the University Hospital of Innsbruck's Department
      of Oral and Maxillofacial Surgery during a period of 6 years 4 months were
      admitted for dental trauma, facial trauma, or both. Records were analyzed for
      cause of injury, age, gender, monthly distribution, frequency, type of injury,
      and frequency of dental trauma in relation to facial injuries and concomitant
      injuries. RESULTS: The incidence of dental injuries with respect to the total
      number of facial injuries was as follows: 57.8% in play and household accidents,
      50.1% in sports accidents, 38.6% in accidents at work, 35.8% in acts of violence,
      34.2% in traffic accidents, and 31% in unspecified accidents. The overall
      incidence revealed was 48.25%. CONCLUSION: Our findings support the fact that in
      the mosaic of traumatic injuries, the frequencies of tooth trauma and its
      sequelae are underestimated and that such trauma and sequelae occur without a
      predictable pattern of intensity and extensiveness. Preventive approaches are the
      sole way to minimize the number of these injuries. Substantial progress made in
      treating facial and dental trauma in the last 2 decades only improves functional
      and esthetic outcomes among the population that has suffered dental injury.

PMID- 9927075
TI  - Thickness of the articular soft tissue of the temporal component in
      temporomandibular joints with and without disk displacement.
AB  - OBJECTIVE: The purpose of this investigation was to test the hypothesis that
      temporomandibular joint disk displacement is associated with significant
      functional adaptive changes of the articular soft tissue of the articular
      eminence. STUDY DESIGN: Thirteen temporomandibular joint autopsy specimens with
      normal superior disk position and 12 with complete anterior disk displacement
      were cryosectioned, and sections were stained and photographed. At a
      magnification of x20 the soft tissue was measured (1) at the inflection point,
      (2) on the posterior slope, (3) at the apex, and (4) on the anterior slope of the
      articular eminence. RESULTS: Displacement of a deformed or nondeformed
      temporomandibular joint disk without perforation of the posterior disk attachment
      was associated with significantly increased thickness of the articulating soft
      tissue at the apex and on the posterior and anterior slopes of the articulating
      eminence. When disk displacement was associated with a perforation of the
      posterior disk attachment, the soft tissue was not significantly thicker than in
      joints with normal superior disk position. CONCLUSIONS: Increase in articulating
      soft tissue thickness is interpreted as an adaptive mechanism to maintain the
      condyle path and withstand excessive loading at interposition of the
      temporomandibular joint components. When the plasticity of the tissues is
      surpassed, the adaptation will be thwarted and replaced by tissue breakdown.

PMID- 9927077
TI  - Comparative study of intramuscular and intraskeletal osteogenesis by recombinant
      human bone morphogenetic protein-2.
AB  - OBJECTIVE: The purpose of this study was to compare the osteoinducing activity of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) at intramuscular and
      intraskeletal sites in rats. STUDY DESIGN: Five tg of rhBMP-2 was implanted into
      the right calf muscle of each of 20 rats and into a hole (4 mm in diameter, 1.5
      mm in depth) that was made in the mandibular body of each of 20 other rats, with
      atelopeptide type I collagen as a carrier. The alkaline phosphatase activity and
      calcium content were quantitatively analyzed 1, 3, 7, and 21 days after the
      implantation of rhBMP-2 into either mandibular bone (in the intraskeletal group)
      or calf muscle (in the intramuscular group). The new bone formation was evaluated
      histologically 21 days after implantation. RESULTS: On days 1 and 3, the alkaline
      phosphatase activity and calcium content in the intraskeletal group showed no
      significant differences from those in the intramuscular group. On the 7th and
      21st days after implantation, however, the alkaline phosphatase activity and
      calcium content in the intraskeletal group were significantly higher than those
      in the intramuscular group. Histometry of the microscopic views showed that the
      mean trabecular area was 0.87 mm2 in the intramuscular group and 2.66 mm2 in the
      intraskeletal group. CONCLUSIONS: These results suggest that the new bone
      formation stimulated by rhBMP-2 in the intraskeletal group was greater than in
      the intramuscular group.

PMID- 9927078
TI  - Ultrasonography in the diagnosis of palatal tumors.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of
      ultrasonography for the preoperative evaluation of palatal salivary gland tumors.
      STUDY DESIGN: Eleven surgically treated patients with salivary gland tumors of
      the palate were examined retrospectively. Intraoral ultrasonic scanning
      examinations were performed with a 10-MHz transducer. RESULTS: The
      ultrasonographically well-delimited tumors had a complete capsule histologically,
      whereas the poorly delimited tumors had no capsule or only an incomplete capsule.
      The tumors that had a reinforced posterior wall echo were associated with
      pressure bone absorption, and the tumors that had a reinforced posterior echo
      were associated with bone destruction. Echograms of the tumors were classified
      into 4 types on the basis of the internal echoes. CONCLUSIONS: Intraoral
      ultrasonography of palatal tumors can be used to determine the localization and
      condition of the tumors by close analysis of the echogram. The internal echo
      pattern on the ultrasonogram of a palatal tumor was found to reflect the
      pathologic structure of the tumor. Ultrasonography can therefore be a quite
      useful technique for the preoperative evaluation of palatal salivary gland
      tumors.

PMID- 9927079
TI  - In vitro activities of antimicrobial agents against Candida species.
AB  - OBJECTIVE: Antimicrobial mouthrinses may represent a valid alternative to topical
      antifungal agents. However, the action of antimicrobials could be affected by the
      different ingredients incorporated into mouthrinse products. The purpose of the
      present study was to investigate the in vitro antifungal and fungicidal
      activities of antimicrobials alone. STUDY DESIGN: A broth macrodilution method
      was used to determine the minimum inhibitory concentration of 4 antimicrobial
      agents against Candida species. Minimum fungicidal concentration was also
      determined. RESULTS: All antimicrobials showed antifungal activity against all
      tested organisms, but cetylpyridinium chloride received significantly lower
      minimum inhibitory concentrations (P < .005). Cetylpyridinium chloride also
      showed a greater fungicidal activity than chlorhexidine digluconate and
      hexetidine (P< .005), whereas sanguinarine chloride appeared to be less
      fungicidal against most of the isolates tested. CONCLUSIONS: These findings
      suggest that cetylpyridinium chloride may be used as a topical antifungal agent.
      Clinical trials are now required to assess its value in the management of oral
      candidosis.

PMID- 9927080
TI  - Clarithromycin as a single-modality treatment in mycobacterial avium
      intracellular infections.
AB  - Atypical mycobacterial infections are frequently associated with chronic cervical
      lymphadenopathy, particularly in children between 1 and 5 years of age. The
      treatment of choice is regarded to be "optimal" surgical treatment, which often
      requires wide excision of affected lymph nodes. Although surgical excision is a
      reliable treatment, it has obvious drawbacks. Because branches of the peripheral
      facial nerve may be intimately involved in the inflammatory reaction, damage is a
      potential complication. In addition, keloid scars and wound breakdown are
      possible complications. Successful drug treatment is hampered by poor
      susceptibility of the Mycobacterium avium-intracellulare and Mycobacterium
      scrofulaceum strains to antimicrobial drugs. Reports of results with
      clarithromycin in the treatment of patients with AIDS who are infected with the M
      avium complex, however, are promising. The cases of 2 children with infections
      caused by the M avium complex, resulting in preauricular and cervical
      lymphadenitis, are described. Treatment with clarithromycin as a monotherapy led
      to complete healing without recurrence.

PMID- 9927081
TI  - The influence of hypothyroidism and thyroid replacement therapy on stimulated
      parotid flow rates.
AB  - OBJECTIVE: The purpose of this study was to determine, through use of cross
      sectional and longitudinal data, whether hypothyroidism and its treatment with
      thyroid hormones have a significant effect on the production of stimulated
      parotid flow rates. STUDY DESIGN: From the Baltimore Longitudinal Study of Aging
      (NIA, NIH), subjects with hypothyroidism taking and not taking thyroid
      replacement therapy were evaluated for the production of 2% citrate-stimulated
      parotid saliva in a cross-sectional and longitudinal investigation. Comparisons
      were made with nonmedicated healthy control subjects. RESULTS: Cross-sectional
      analyses revealed that stimulated parotid flow rates were not significantly
      different between healthy controls, subjects with hypothyroidism on thyroid
      replacement therapy, and subjects with hypothyroidism not on thyroid replacement
      therapy. In general, longitudinal analyses revealed no significant differences
      over time in stimulated parotid flow rates between healthy controls and subjects
      with hypothyroidism. CONCLUSIONS: Hypothyroidism and the concomitant use of
      thyroid replacement therapy do not cause significant changes in the production of
      stimulated parotid saliva.

PMID- 9927082
TI  - Leukoplakia of the maxillary vestibule--an association with Viadent?
AB  - OBJECTIVE: This report investigates a possible correlation between chronic use of
      Viadent products and the subsequent development of leukoplakia in the maxillary
      vestibule. STUDY DESIGN: A retrospective review of 88 patients with leukoplakia
      of the maxillary vestibule is presented. Prevalence of Viadent use was determined
      in this group and in a group of 100 randomly selected adults who presented
      themselves for routine preadmission screening at a dental school. RESULTS: Of the
      patients diagnosed with leukoplakia of the maxillary vestibule, 84.1% reported
      having used Viadent, whereas the prevalence of use was only 3% in the 100
      randomly selected adults. CONCLUSIONS: Use of Viadent products appears to be
      associated with an increased prevalence of leukoplakia in the maxillary
      vestibule.

PMID- 9927083
TI  - Unusual form of recurrent giant cell granuloma of the mandible and lower
      extremities in a patient with neurofibromatosis type 1.
AB  - We report on a girl with familial neurofibromatosis type 1 (Nf1) who at age 11
      had multiple osteolytic lesions of the right mandible and the distal femoral and
      proximal tibial metaphyses bilaterally. No other skeletal component was affected,
      and no abnormalities were present on skeletal radiographs of her parents.
      Histologic examination of the mandibular and right femoral lesions revealed a
      "multinucleated giant cell process." Results of repeated routine laboratory and
      bone metabolic studies were within normal limits. The lack of reliable histologic
      criteria and the diagnostic problems in distinguishing among central giant cell
      granulomata, giant cell tumors of the jaw, cherubism, brown tumors resulting from
      (occult) hyperparathyroidism, Jaffe-Campanacci syndrome, McCune-Albright
      syndrome, Noonan-like/multiple giant cell lesion syndrome, and multiple
      nonossifying fibromas of bone are discussed.

PMID- 9927084
TI  - Malignant tumors of Stensen's duct.
AB  - A rare case of squamous cell carcinoma arising in Stensen's duct is reported. The
      literature concerning malignant neoplasia originating in this site is reviewed,
      with attention given to the histopathologic diversity of neoplasms occurring in
      the duct, criteria for determination of origin in the duct, and outcomes of
      therapy.

PMID- 9927085
TI  - Intraosseous leiomyoma of the mandible.
AB  - An intraosseous leiomyoma arising within the mandible was diagnosed in a 24-year
      old woman. Clinically, a nodular swelling of the lower border of the mandible was
      noted. Radiographically, a unilocular ellipsoid radiolucency, loss of the lower
      border of the mandible, and tooth resorption were observed. The mitotic count was
      0.4 per 10 high-power fields, which supported the benign nature of the tumor. The
      clinical and histologic parameters for distinguishing between benign and
      malignant smooth muscle neoplasms are discussed.

PMID- 9927086
TI  - Bactericidal effect of electrolyzed neutral water on bacteria isolated from
      infected root canals.
AB  - OBJECTIVE: The purposes of this study were to examine the time-related changes in
      pH, oxidation-reduction potential, and concentration of chlorine of electrolyzed
      neutral water and to evaluate the bactericidal effect of electrolyzed neutral
      water against bacteria from infected root canals. STUDY DESIGN: Various
      properties of electrolyzed neutral water--pH value, oxidation-reduction
      potential, and concentration of chlorine--were measured at different times after
      storage of the water in the open state, the closed state, or the closed-and-dark
      state. The bactericidal effect of the various electrolyzed neutral water samples
      was then tested against 17 strains of bacteria, including 15 strains isolated
      from infected canals, as well as against 1 strain of fungus. Each bacterial or
      fungal suspension was mixed with electrolyzed neutral water, and the 2 substances
      were reacted together for 1 minute. After incubation for 1 to 7 days, the
      bactericidal effect of the electrolyzed neutral water was determined. RESULTS:
      The pH value and oxidation-reduction potential of electrolyzed neutral water
      remained almost unchanged when the water was stored in a dark, closed container.
      However, the concentration of chlorine decreased from 18.4 ppm to 10.6 ppm.
      Electrolyzed neutral water showed a bactericidal or growth-inhibitory effect
      against the bacteria. CONCLUSIONS: The results indicate that electrolyzed neutral
      water maintains a constant pH and oxidation-reduction potential when kept in a
      closed container without light and that it exhibits a bacteriostatic/bactericidal
      action against isolates obtained from infected root canals.

PMID- 9927087
TI  - Pulpal blood-flow characteristics of maxillary tooth morphotypes as assessed with
      laser Doppler flowmetry.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of tooth
      morphotype on intraindividual and interindividual variations of baseline data as
      well as on temporal variations between testing intervals in the assessment of
      pulpal blood-flow by means of laser Doppler flowmetry. STUDY DESIGN: In 14
      volunteers, maxillary incisors, canines, premolars, and first molars were
      investigated bilaterally by laser Doppler flowmetry to assess local pulpal blood
      flow values. Measurements in perfusion units were taken during 3 sessions, with a
      time interval of 7 days between sessions. RESULTS: Intraindividual comparisons of
      tooth morphotype-related pulpal blood-flow values revealed significant
      differences only for the first molar, whereas significant interindividual
      differences were found for the lateral incisor, canine, premolars, and first
      molar. Pulpal blood-flow values for the second premolar (11.1 perfusion units)
      were significantly higher and those for the central incisor (7.6 perfusion units)
      significantly lower than those for the lateral incisor (9.2 perfusion units) and
      first molar (9.4 perfusion units). In contrast, measurements at the lateral
      incisor, first premolar, and first molar did not differ significantly (P > .05).
      Multiple testing showed no statistically significant effect on tooth morphotype
      related pulpal blood-flow measurements. CONCLUSIONS: The findings indicate that
      contralateral incisors, canines, and premolars are appropriate intraindividual
      controls for local pulpal blood-flow recordings. Other studies may identify the
      effect of environmental and technique-related factors on the assessment of local
      pulpal blood-flow values.

PMID- 9927088
TI  - Ultrasonographic cross-sectional characteristics of muscles of the head and neck.
AB  - OBJECTIVE: Computed tomography and magnetic resonance imaging are the common
      techniques for evaluating cross-sectional areas and volumes of human jaw muscles.
      Because computed tomography has the disadvantage of showing cumulative biological
      effects and because MRI poses a problem in terms of clinical availability and
      cost, the purpose of this study was to determine whether ultrasonography could be
      used to measure local linear cross-sectional dimensions of muscles of the head
      and neck. STUDY DESIGN: In 46 patients with signs and symptoms of
      temporomandibular disorders, the anterior temporalis, anterior masseter, deep
      masseter, anterior digastric, posterior digastric, and sternocleidomastoid
      muscles were measured bilaterally by ultrasonography to assess linear local cross
      sectional dimensions. Measurements were made in 2 sessions with a time interval
      of at least 5 minutes. Data were analyzed for reliability and variability through
      use of the intraclass correlation coefficient (ICC) and the repeatability
      coefficient (RC). To assess local muscle asymmetry patterns, the absolute
      asymmetry index was used, with the mean maximum muscle diameters of the
      respective right and left sides calculated from 3 consecutive measurements.
      RESULTS: Satisfactory visualization of muscles was obtained in 93.8% of 1104
      imaging procedures. For the ultrasound measurements there was a significant
      difference in local cross-sectional dimensions between the first and second
      sessions for the anterior temporalis muscle only (P < .01). Acceptable intrarater
      reliabilities were obtained for the deep masseter (ICC = 0.92), anterior
      digastric (ICC = 0.91), and sternocleidomastoid (ICC = 0.86) muscles, whereas
      evaluation of the posterior digastric (ICC = 0.74), anterior masseter (ICC =
      0.72), and anterior temporalis (ICC = 0.70) muscles was associated with moderate
      reliability. Variability of repeated measurements was found to be acceptable for
      the anterior temporalis (RC = 0.32 mm) and posterior digastric (RC = 0.48 mm)
      muscles. Analysis of muscle site-related local cross-sectional dimensions showed
      a significant difference between the right and left sides for the deep masseter
      muscle only (P < .05). The study population investigated revealed mean asymmetry
      indices ranging from 5.3% for the anterior digastric muscle to 8.7% for the deep
      masseter muscle. CONCLUSIONS: Ultrasonography may prove to be a reliable
      diagnostic technique for the evaluation of cross-sectional dimensions and areas
      of muscles of the head and neck.

PMID- 9927089
TI  - Cemento-osseous dysplasia of the jaws in 54 Japanese patients: a radiographic
      study.
AB  - OBJECTIVE: The aim of this study was to describe the radiographic patterns of
      cemento-osseous dysplasia. STUDY DESIGN: Fifty-four patients affected with benign
      fibro-osseous jaw lesions that showed periapical radiopacities and/or
      radiolucencies in a focal or a multiplex form were studied. The clinical,
      radiographic, and histopathologic features of the patients with cemento-osseous
      dysplasia were retrospectively studied. Radiographic features of the cemento
      osseous dysplasia lesions were classified according to the appearance of
      calcified bodies. Radiographic visibility of periodontal ligament spaces of
      related teeth was assessed. RESULTS: Forty-nine (91 %) of the 54 patients were
      women. The mean age of the total group was 50.8 years, and that of the male group
      was 64.6 years. The cemento-osseous dysplasia lesions could be classified into 6
      types radiographically. Eighteen patients had at least 2 or more types of cemento
      osseous dysplasia lesions. Of 147 related teeth, 142 had periodontal ligament
      spaces clearly visible. Six of 9 patients who had a total of 25 teeth with active
      hypercementosis showed concomitant occurrence of other types of cemento-osseous
      dysplasia lesions. Biopsy specimens showed various amounts of bonelike and
      cementumlike tissues. CONCLUSIONS: It is likely that cemento-osseous dysplasia
      consists of 3 variations of a single entity, all with the same unknown cause. In
      one variation, the entity originates from the periodontium; in another, it is of
      medullary bone origin; and in the third it results from the simultaneous
      involvement of both tissues.

PMID- 9927090
TI  - Assessment of image quality in dental radiography, part 1: phantom validity.
AB  - OBJECTIVE: The purpose of this study was to describe and validate an image
      quality phantom to be used in dental radiography for comparison of film and
      digitally acquired images. STUDY DESIGN: An aluminum block of 12 steps, with 7
      holes in each step, was covered by acrylic blocks. This phantom was radiographed
      with Kodak Ultra-speed and Ektaspeed Plus films at 70, 65, and 60 kVp with the
      whole exposure range available. All together, 50 dental films were randomly
      sequenced and presented to 7 observers. The average number of perceptible holes
      from all steps was plotted against exposure for each tube voltage and film type,
      generating a modified perceptibility curve. The tentative optimum exposure level
      was determined from perceptibility curves in each experimental condition and
      compared with that determined by means of the standard aluminum stepwedge and the
      preset time of the x-ray machine. The density range of this phantom at the
      optimum exposure was compared with that of clinical dental radiographs. Validity
      of the phantom was evaluated according to the optimum exposure level from the
      modified perceptibility curves and the overall density range. Finally, the
      average maximum numbers of perceptible holes at the tentative optimum exposure
      level were compared for each tube voltage and film type. The statistical test
      used was a 2-way factorial analysis of variance. RESULTS: The exposure at the
      perceptibility curve peak approximated that obtained by means of the standard
      aluminum step-wedge and the time preset by the manufacturer. The overall density
      range at the perceptibility curve peak covered the clinical density range for
      each tube voltage and film type. There were no statistically significant
      differences between film types or among tube voltages. CONCLUSIONS: The x-ray
      attenuation range for this phantom seemed to approximate clinical conditions. In
      addition, differences in image quality could be quantitatively evaluated by means
      of the number of the holes seen in the phantom.

PMID- 9927091
TI  - Assessment of image quality in dental radiography, part 2: optimum exposure
      conditions for detection of small mass changes in 6 intraoral radiography
      systems.
AB  - OBJECTIVE: The purpose of this study was to compare 2 film systems and several
      digital intraoral systems with regard to visual image quality through use of a
      test phantom developed for this purpose. STUDY DESIGN: The detectors used for
      digital imaging were as follows: Computed Dental Radiography (CDR), Digora,
      Dixel, and Sens-A-Ray without scintillator layer. Two types of digital images
      were prepared for the observer performance test: one with original gray scales
      and another with contrast enhancement. Images with and without enhancement from
      the 4 systems were displayed to 7 observers. The change in the average number of
      perceptible holes was plotted against exposure, and modified perceptibility
      curves were created and compared with curves for the film systems. The exposure
      level at which the maximum number of holes was perceived was defined to be
      optimum. The optimum exposure levels were determined for each digital system and
      compared with that of the film systems. At the optimum exposure, the average
      maximum numbers of perceptible holes in each digital system with and without
      contrast enhancement were compared with the maximum numbers for the film systems.
      The minimum exposure levels were determined to be those at which the number of
      perceptible holes exceeded the number for film, and the possibility of exposure
      reduction was evaluated. RESULTS: All digital systems except the Digora system
      showed lower optimum exposures than E-speed film. In all digital images without
      enhancement, however, the maximum number of perceptible holes was significantly
      lower than that for the film systems at that exposure. With contrast enhancement,
      all digital systems except the Sens-A-Ray system showed visibility superior to
      that of the film systems. With the CDR, Digora, and Dixel systems, exposures
      could be further reduced by a considerable amount, with greater retention of
      information than was associated with film. CONCLUSIONS: Our results strongly
      suggest that digital systems, if properly used, can exceed film systems in the
      detection of small mass changes.

PMID- 9927092
TI  - Do we need a clinical decision rule for the discontinuation of cardiac arrest
      resuscitations?

PMID- 9927093
TI  - Multi-item "instruments" vs Virginia Apgar's principles of clinimetrics.

PMID- 9927094
TI  - Derivation of a clinical decision rule for the discontinuation of in-hospital
      cardiac arrest resuscitations.
AB  - BACKGROUND: Most patients undergoing in-hospital cardiac resuscitation will not
      survive to hospital discharge. OBJECTIVE: To derive a decision rule permitting
      the discontinuation of futile resuscitation attempts by identifying patients with
      no chance of surviving to hospital discharge. PATIENTS AND METHODS: Patient,
      arrest, and outcome data for 1077 adult patients undergoing in-hospital cardiac
      resuscitation was retrieved from 2 randomized clinical trials involving 5
      teaching hospitals at 2 university centers. Recursive partitioning was used to
      identify a decision rule using variables significantly associated with death in
      hospital. RESULTS: One hundred three patients (9.6%) survived to hospital
      discharge. Death in hospital was significantly more likely if patients were older
      than 75 years (P<.001), the arrest was unwitnessed (P = .003), the resuscitation
      lasted longer than 10 minutes (P<.001), and the initial cardiac rhythm was not
      ventricular tachycardia or fibrillation (P<.001). All patients died if there was
      no pulse 10 minutes after the start of cardiopulmonary resuscitation, the initial
      cardiac rhythm was not ventricular tachycardia or fibrillation, and the arrest
      was not witnessed. As a resuscitation rule, these parameters identified all
      patients who survived to hospital discharge (sensitivity, 100%; 95% confidence
      interval, 97.1%-100%). Resuscitation could have been discontinued for 119 (12.1%)
      of 974 patients who did not survive, thereby avoiding 47 days of
      postresuscitative care. CONCLUSIONS: A practical and highly sensitive decision
      rule has been derived that identifies patients with no chance of surviving in
      hospital cardiac arrest. Prospective validation of the rule is necessary before
      it can be used clinically.

PMID- 9927095
TI  - Preoperative vs postoperative initiation of low-molecular-weight heparin
      prophylaxis against venous thromboembolism in patients undergoing elective hip
      replacement.
AB  - BACKGROUND: Although preoperative and postoperative initiation of prophylaxis for
      deep vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) are
      effective, the relative effectiveness and safety of these approaches is unknown.
      In the absence of a published definitive level 1 trial addressing this question,
      a meta-analysis is appropriate. OBJECTIVE: To report a meta-analysis comparing
      preoperative with postoperative initiation of prophylaxis of DVT in patients
      undergoing elective hip replacement. METHODS: Relevant trials were identified,
      and potential biases in the meta-analysis were minimized by analyzing all
      rigorously performed randomized trials that met all of the following criteria for
      conduct of the trial: (1) double-blind design, (2) objective documentation of the
      frequencies of DVT by ascending contrast venography, (3) venography performed
      before or at the time of discharge from the hospital, (4) initiation of the same
      LMWH preoperatively or postoperatively in dosages shown to be effective, (5)
      compliance with the criteria for a level 1 trial, and (6) objective documentation
      of major and minor bleeding according to strict criteria. RESULTS: Treatment with
      LMWH initiated preoperatively was associated with a DVT frequency of 10.0%
      compared with a frequency of 15.3% when the LMWH was initiated postoperatively (P
      = .02, Fisher exact test). Major bleeding was less frequent in patients receiving
      preoperatively initiated LMWH than in patients receiving postoperatively
      initiated LMWH (0.9%, vs. 3.5%; P = .01, Fisher exact test). CONCLUSIONS: Our
      findings support the need for a randomized comparison of preoperative and
      postoperative initiation of pharmacological prophylaxis of DVT. Such a trial
      would resolve the divergent practices for DVT prophylaxis between Europe and the
      North American countries, the United States and Canada, and would affect the
      treatment for thousands of patients on both continents.

PMID- 9927096
TI  - Clinical and economic effects of population-based Helicobacter pylori screening
      to prevent gastric cancer.
AB  - BACKGROUND: Helicobacter pylori infection has been identified as a risk factor
      for certain types of gastric cancer. However, the extent to which H. pylori
      eradication decreases the risk of gastric cancer is unknown, raising the question
      of whether population-based H. pylori screening should be undertaken. OBJECTIVE:
      To compare clinical and economic effects of H. pylori screening, with and without
      confirmatory testing, with no screening to prevent gastric cancer. DESIGN:
      Decision analysis incorporating a Markov simulation. PATIENTS: Simulated cohorts
      of men and women with varying risk of gastric cancer. INTERVENTION: Three
      strategies were evaluated: (1) no screening; (2) H. pylori serologic testing,
      treat those positive for H. pylori, no follow-up testing; and (3) H. pylori
      serologic testing, treat those positive for H. pylori, followed by a test to
      confirm H. pylori eradication, retreat those who test positive. In the principal
      analysis, the risk of gastric cancer after H. pylori eradication was assumed to
      be similar to that for those without H. pylori infection. Scenarios with less
      optimistic assumptions regarding risk reduction of cancer were evaluated. MAIN
      OUTCOME MEASURES: Gastric cancer rates, discounted cost per life-year saved.
      RESULTS: If H. pylori eradication reduced the risk of cancer to that of people
      never infected, both H. pylori intervention strategies reduced gastric cancer
      rates so that each yielded at least 12 additional life-years per 1000 40-year-old
      white men screened when compared with no screening. Helicobacter pylori serologic
      testing without posttreatment confirmatory testing resulted in the lowest cost
      per additional life-year saved (S6264). The cost-effectiveness of the H. pylori
      screening strategies varied substantially as the level of risk reduction of
      cancer was varied, but remained cost-effective even at moderate rates (<30%) of
      excess risk reduction of cancer in all cohorts evaluated. CONCLUSIONS: Population
      based H. pylori screening has the potential to produce important health benefits
      at a reasonable cost at moderate rates of excess risk reduction of cancer.
      Controlled studies are necessary to confirm and quantify the impact of H. pylori
      eradication on the risk of gastric cancer.

PMID- 9927097
TI  - Screening for Helicobacter pylori and nonsteroidal anti-inflammatory drug use in
      medicare patients hospitalized with peptic ulcer disease.
AB  - BACKGROUND: Peptic ulcer disease has well-defined causes, with most cases related
      to Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use.
      OBJECTIVES: To report performance rates on measures of care related to peptic
      ulcer disease in hospitalized Medicare patients and to identify improvement
      opportunities. METHODS: Retrospective study of 2267 Medicare beneficiaries
      hospitalized with peptic ulcer disease. Data were obtained from 2 sources:
      medical records (n = 1580) from 80 hospitals--16 hospitals in each of 5 states
      (Alabama, Florida, Louisiana, Tennessee, and Texas)-and a national random sample
      (n = 687). Three measures of care were evaluated: (1) rate of diagnostic
      screening or treatment for H. pylori infection, (2) rate of screening for
      nonsteroidal anti-inflammatory drug use on admission to the hospital, and (3)
      rate of assessment of risk factors for recurrence. RESULTS: The rate of screening
      or treatment for H. pylori infection was 52.9% to 59.8% among the 5 states and
      55.6% in the national random sample. The rate of screening for nonsteroidal anti
      inflammatory drug use was 64.6% to 75.4% among the states and 73.4% in the
      national random sample. The rate of assessment at discharge from the hospital for
      additional risks for ulcer recurrence was 66.1% to 73.6% among the states and
      70.9% in the national random sample. CONCLUSIONS: Based on hospital records,
      slightly more than half of the Medicare patients admitted with diagnoses studied
      are being considered for H. pylori eradication. If recurrence of this disease is
      to be reduced, physicians must adopt current screening and treatment
      recommendations.

PMID- 9927098
TI  - For COPD a combination of ipratropium bromide and albuterol sulfate is more
      effective than albuterol base.
AB  - BACKGROUND: A combination metered-dose inhaler aerosol containing ipratropium
      bromide and albuterol sulfate has been reported to be more effective than either
      of its components in patients with chronic obstructive pulmonary disease. The
      dose of albuterol sulfate is equal in moles per liter to the dose of albuterol
      base used in the commercially available metered-dose inhalers. OBJECTIVE: To
      compare the safety and efficacy of the combination of ipratropium bromide and
      albuterol sulfate with a commonly prescribed albuterol metered-dose inhaler
      containing albuterol base alone. METHODS: Investigators at different sites
      performed a double-blind, 29-day trial involving 357 patients with chronic
      obstructive pulmonary disease. Efficacy measurements were taken at 15, 30, and 60
      minutes after treatment with study medication and then hourly up to 6 hours on
      days 1 and 29 of the trial. The primary end point was improvement in forced
      expiratory volume in 1 second. Clinical status was followed up and safety
      monitoring was also performed. RESULTS: The combination produced a significantly
      greater peak and mean improvement in forced expiratory volume in 1 second over
      albuterol base alone on both test days. Similar changes were seen with forced
      vital capacity. Evaluations of clinical status were better for patients receiving
      combination therapy, and some improvements were statistically significant. The
      overall incidence of adverse effects was similar in the 2 treatment groups.
      CONCLUSION: We conclude that a combination of ipratropium bromide and albuterol
      sulfate is more effective at improving pulmonary function than albuterol base
      alone, with no potentiation of adverse effects.

PMID- 9927099
TI  - Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a
      population-based study.
AB  - BACKGROUND: Previous observational studies have provided limited information on
      the effect of specific nonsteroidal anti-inflammatory drugs (NSAIDs) and
      different patterns of use (duration and dose) on the incidence of colorectal
      cancer. OBJECTIVE: To determine how patterns of use (duration, dose, and specific
      drug) of NSAIDs affect incidence of colorectal cancer. DESIGN: Population-based
      retrospective cohort study. SETTING: Tennessee Medicaid Program, 1985-1992.
      SUBJECTS: Enrollees (n = 104217) aged 65 years or older with at least 5 years of
      enrollment. MAIN OUTCOME MEASURES: Incident histologically confirmed colorectal
      cancer. RESULTS: Users of nonaspirin NSAIDs for at least 48 months of the
      previous 5 years had a relative risk (RR) of 0.49 (95% confidence interval [CI],
      0.24-1.00) for colon cancer when compared with those with no use of NSAIDs. Among
      those with more than 12 months of cumulative use, those using NSAIDs in the past
      year (recent users) had an RR of 0.61 (95% CI, 0.48-0.77), whereas those with no
      recent use had an RR of 0.76 (95% CI, 0.50-1.15). No specific NSAID offered a
      unique protective effect and low doses of NSAIDs appeared to be at least as
      effective as higher doses. Protection was most pronounced for right-sided
      lesions. The RR among recent users with more than 12 months of cumulative use was
      0.81 (95% CI, 0.49-1.32) for rectal cancer, 0.77 (95% CI, 0.55-1.08) for left
      sided colon cancer, and 0.48 (95% CI, 0.34-0.68) for right-sided colon cancer.
      CONCLUSIONS: In this elderly population, long-term use of nonaspirin NSAIDs
      nearly halved the risk of colon cancer. This study was consistent with previous
      studies that suggest that duration of use but not daily dose of NSAIDs is an
      important factor for chemoprevention. Our data also suggest that the protective
      effect is shared by most NSAIDs, and not confined to a small number of these
      drugs.

PMID- 9927100
TI  - Treatment of Q fever endocarditis: comparison of 2 regimens containing
      doxycycline and ofloxacin or hydroxychloroquine.
AB  - BACKGROUND: Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to
      60% of patients. Currently, treatment with a long-term tetracycline and quinolone
      regimen for at least 4 years is recommended, although relapses are frequent.
      METHODS: Between January 1987 and December 1997, the reference treatment of Q
      fever endocarditis was compared with one of doxycycline and hydroxychloroquine
      sulfate. Patients were treated by conventional therapy until May 1991 and then by
      the new regimen. Microimmunofluorescence was used for antibody-level
      determination for diagnosis and follow-up. RESULTS: Thirty-five patients were
      included in the study, 26 males and 9 females. Of 14 patients treated with a
      doxycycline and quinolone combination, 1 died, 7 relapsed (3 were re-treated and
      4 switched to the new regimen), 1 is still being treated, and 5 were considered
      cured using this regimen only. The mean duration of therapy for cure in this
      group was 55 months (median, 60 months). Twenty-one patients received the
      doxycycline and hydroxychloroquine regimen: 1 patient died of a surgical
      complication, 2 are still being treated, 17 were cured, and 1 is currently being
      evaluated. Two patients treated for 12 months but none of the patients treated
      for longer than 18 months relapsed. The mean duration of treatment in this group
      was 31 months (median, 26 months). No significant differences were observed
      between the 2 regimens in terms of death, valve surgery, or tolerance. The
      mortality rate for both regimens in this study was 5%. CONCLUSION: Prescription
      of the doxycycline and hydroxychloroquine combination for at least 18 months
      allows shortening of the duration of therapy and reduction in the number of
      relapses.

PMID- 9927101
TI  - Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in
      patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose,
      multicenter trial. P92-01 Study Group.
AB  - BACKGROUND: Patients with Sjogren syndrome (SS) experience slowly progressive
      infiltration of lacrimal and salivary glands by mononuclear cells. This leads to
      diminished secretions, with resultant symptoms of xerostomia and xerophthalmia.
      Although pilocarpine hydrochloride tablets are currently indicated for the
      treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes
      in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of
      pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes
      caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS:
      After providing written informed consent, 373 patients with primary or secondary
      SS and clinically significant dry mouth and dry eyes were randomized to receive
      2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12
      weeks. Symptoms were assessed by questionnaires with visual analog scales or
      categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A
      significantly greater proportion of patients in the 5-mg pilocarpine group showed
      improvement compared with the placebo group (P< or =.01) in global assessments of
      dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow
      was significantly increased 2- to 3-fold (P<.001) after administration of the
      first dose and was maintained throughout the 12-week study. The most common
      adverse effect was sweating, and no serious drug-related adverse experiences were
      reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily
      (20 mg/d) was well tolerated and produced significant improvement in symptoms of
      dry mouth and dry eyes and other xeroses in patients with SS.

PMID- 9927102
TI  - Protection against influenza after annually repeated vaccination: a meta-analysis
      of serologic and field studies.
AB  - BACKGROUND: According to common recommendations, influenza vaccination should be
      performed annually. It has been suggested that vaccination in previous years
      reduces vaccine efficacy in the long term. OBJECTIVE: To determine whether the
      protection of influenza vaccine decreases when vaccination is repeated annually.
      METHODS: Articles published between 1966 and 1997 were selected from MEDLINE. The
      end point for field studies was the influenza-related morbidity or mortality
      during influenza outbreaks (resulting in field protection rates). The end point
      for serologic studies was exceeding a protective postvaccination hemagglutination
      inhibition titer (serologic protection rates). Protection rate differences
      between groups with single and multiple vaccinations were subjected to meta
      analysis. RESULTS: Seven field studies (including 13 trials) supported the
      hypothesis that protection in multiple-vaccination groups is at least as good as
      that in single-vaccination groups. Ten trials with 5117 observations could be
      subjected to meta-analysis. The pooled protection-rate difference was close to 0
      (1.1%; 95% confidence interval, -0.2% to 2.4%), thus detecting no difference
      between single or multiple vaccination. Twelve serologic studies (including 53
      trials) showed heterogeneous results: 9 trials were significantly in favor of
      single vaccination, and 7 were in favor of multiple vaccination, but in most
      cases, there was no significant difference between the 2 vaccination groups. The
      pooled serologic protection-rate difference from 52 trials (12341 observations)
      was again close to 0 (1.7%; 95% confidence interval, -1.3% to 4.8%). CONCLUSIONS:
      We did not detect any evidence for a decreasing protection with annually repeated
      influenza vaccination. Annual vaccination should not be discouraged in
      populations at risk.

PMID- 9927103
TI  - Compressive cervical myelopathy due to calcium pyrophosphate dihydrate deposition
      disease: report of a case and review of the literature.
AB  - Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory
      arthropathy that is defined by the deposition of CPPD crystals in articular and
      periarticular structures. The deposition of CPPD in hyaline cartilage and
      fibrocartilage leads to the chondrocalcinosis that is characteristic of the
      disease. It can occur independently or in association with any of a number of
      inflammatory or endocrine disorders. This form of crystal-induced arthritis tends
      to affect the peripheral joints, particularly the knees, ankles, shoulders,
      wrists, and second and third metacarpophalangeal joints, but involvement of the
      lumbar spine is not uncommon. Cervical spine disease due to CPPD deposition is,
      however, rare. We report a case of compressive cervical myelopathy due to CPPD
      deposition disease of the cervical spine in a woman with long-standing rheumatoid
      arthritis. We also, from a review of the English-language literature, describe
      the collective reported clinical experience with CPPD deposition disease of the
      cervical spine.

PMID- 9927104
TI  - Switching HIV-1 protease inhibitor therapy: which? When? And why?

PMID- 9927105
TI  - Failure of alcohol reduction to lower blood pressure in the PATHS trial.
      Prevention and Treatment of Hypertension Study.

PMID- 9927106
TI  - Generalist and specialty care.

PMID- 9927107
TI  - Impact of asthma specialists on patient outcomes.

PMID- 9927108
TI  - Reduction of labor costs associated with treating migraine in the workplace.

PMID- 9927109
TI  - Evolution of erythropoietin and blood management in orthopedics. Introduction.

PMID- 9927110
TI  - An open-label, randomized study to compare the safety and efficacy of
      perioperative epoetin alfa with preoperative autologous blood donation in total
      joint arthroplasty.
AB  - A multicenter, randomized, open-label, parallel-group study was conducted to
      compare the safety and efficacy of perioperative recombinant human erythropoietin
      (Epoetin alfa) with the safety and efficacy of preoperative autologous donation
      (PAD) in total joint arthroplasty. A total of 490 patients scheduled for total
      joint (i.e., hip or knee) surgery and having hemoglobin (Hb) levels > or = 11 to
      < or = 13 g/dL were randomized to receive weekly doses of subcutaneous Epoetin
      alfa on preoperative Days -21, -14, and -7, and on the day of surgery, or to
      participate in a PAD program. The mean baseline Hb level in both groups was
      12.3+/-0.6 g/dL, increasing to 13.8 g/dL in the Epoetin alfa-treated group and
      decreasing to 11.1 g/dL in the PAD group before or on the day of surgery. In the
      PAD group, 156/219 (71.2%) patients were transfused with autologous blood, and
      42/219 (19.2%) patients were transfused with allogeneic blood. A smaller
      proportion, 27/209 (12.9%) patients, in the Epoetin alfa-treated group were
      transfused with allogeneic blood (P = .078 compared with the PAD group).
      Moreover, patients in the PAD group received a total of 325 units of blood (79
      allogeneic units and 246 autologous units) compared with patients in the Epoetin
      alfa group who received a total of 54 units of blood. The mean postoperative Hb
      level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD
      group. Compared with the PAD arm, mean Hb levels measured preoperatively,
      postoperatively on Day 1, and at discharge visits were significantly greater in
      the Epoetin alfa-treated arm (P < .0001 ).

PMID- 9927111
TI  - Integrated analysis of thrombotic/vascular event occurrence in epoetin alfa
      treated patients undergoing major, elective orthopedic surgery.
AB  - Data from four prospective, multicenter, randomized studies involving 869 major,
      elective orthopedic surgery patients were examined by means of a retrospective
      integrated analysis to evaluate whether perioperative Epoetin alfa use was
      associated with the occurrence of thrombotic/vascular events. The incidence of
      thrombotic/vascular events was similar between 619 patients treated with Epoetin
      alfa and 250 patients receiving placebo (7.4% versus 8.0%, respectively).
      Regression analyses identified age, cardiac history, hypertension, and cardiac
      medications, but not Epoetin alfa, as risk factors for thrombotic/vascular
      events. The analysis did not implicate an increase in the rate of rise in
      hematocrit or maximum hematocrit obtained prior to surgery as contributors to
      thrombotic events. Thus, Epoetin alfa, which enhances preoperative erythropoiesis
      and increases hematocrit, did not affect the probability of thrombotic/vascular
      events.

PMID- 9927112
TI  - Assessment of postoperative vigor in patients undergoing elective total joint
      arthroplasty: a concise patient- and caregiver-based instrument.
AB  - Assessment of early postoperative recuperative power (i.e., vigor and functional
      ability) in surgery patients is considered to be important for optimizing patient
      rehabilitation, discharge planning, and health system resource utilization.
      However, no broadly accepted method of patient assessment has been available to
      measure these parameters. Therefore, a panel of experts was assembled to design
      an instrument to assess recuperative power in the total joint arthroplasty
      setting. The instrument consists of both subjective, patient-based, preoperative
      and postoperative, fixed-ended questions and objective, caregiver-based measures
      of patient function (i.e., muscle strength and hematocrit [HCT]). The prototype
      instrument employed the vitality subscale of the Short Form-36 (SF-36), the
      activities of daily living items from the Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC-ADL), as well as three novel scales: Well-being,
      Ready to resume activities, and Ready to leave the hospital. The instrument was
      tested in 65 patients at two medical centers. The reliability and validity of the
      three novel psychometric scales were tested by measuring internal consistency and
      validity by comparison with the standard scales. Postoperative patient Well-being
      and Ready scales correlated strongly with muscle strength (P < .01), while
      postoperative HCT correlated with muscle strength (r = 0.4) and Ready scale (P <
      .01). This analysis suggested that patient well-being and readiness to resume
      normal activities may be the best surrogates of patient vigor and that these
      parametric assessments correlate well with functional and laboratory measures of
      vigor (i.e., muscle strength and HCT). Based on these findings, the final
      instrument (Version 4.2) consists of a patient questionnaire that can be
      completed within approximately 5 minutes (12 preoperative and 14 postoperative
      questions), and a caregiver questionnaire that includes two objective functional
      tests: muscle strength and HCT. In conclusion, postoperative vigor may be able to
      be assessed with a concise, patient-based instrument and may provide valuable
      information for rehabilitation and discharge planning. The utility of this
      instrument is currently being assessed in a prospective clinical study.

PMID- 9927113
TI  - Blood management experience: relationship between autologous blood donation and
      transfusion in orthopedic surgery.
AB  - Preoperative autologous donation (PAD) is commonly used for patients undergoing
      elective total joint arthroplasty; however, PAD is associated with increased
      overall transfusion rates and may not be cost-effective for all patients. A
      retrospective analysis was conducted on a series of 1405 patients undergoing
      unilateral or bilateral total hip or total knee arthroplasty at The Hospital for
      Special Surgery to determine the effect of PAD on transfusion outcomes. Eighty
      three percent of patients predonated blood (1 unit to 3 units). Transfusions
      occurred in 82% of PAD participants and in only 50% of nondonors. The allogeneic
      transfusion rates were 8% for PAD participants and 50% for nondonors. Thirty-four
      percent to 45% of donated autologous units were discarded. Hemoglobin
      concentrations measured prior to surgery were inversely related to frequency of
      allogeneic transfusion. These data underscore the importance of hemoglobin levels
      in blood management planning. This information can be useful for formulating
      rational, cost-effective blood management guidelines.

PMID- 9927114
TI  - The predictive power of baseline hemoglobin for transfusion risk in surgery
      patients.
AB  - Preoperative hemoglobin concentration may be an important predictor of
      transfusion risk in surgical procedures with significant expected blood loss.
      Contemporary studies investigating transfusion risk with regard to the
      relationship between perioperative administration of Epoetin alfa and baseline
      hemoglobin provide data to test this hypothesis. The predictive power of seven
      preoperative variables (hemoglobin concentration, age, erythropoietin level,
      ferritin concentration, serum iron, total iron-binding capacity, and predicted
      blood volume) on transfusion risk was examined via retrospective logistic
      regression analysis of 276 orthopedic surgical patients. In the two studies used
      to perform the regression analysis, patients were treated daily with either
      Epoetin alfa or placebo. Based on the retrospective analyses, a prospective study
      was conducted to validate the hypothesis. Of the seven variables evaluated,
      baseline hemoglobin concentration and predicted blood volume were significantly
      predictive of transfusion risk in both Epoetin alfa- and placebo-treated
      patients. Further, an inverse correlation between hemoglobin concentration and
      transfusion risk was demonstrated in placebo-treated patients. Placebo-treated
      patients with hemoglobin > 10 to < or = 13 g/dL had an approximately twofold
      greater risk of transfusion than patients with hemoglobin > 13 g/dL. In contrast
      to placebo treatment, Epoetin alfa significantly reduced transfusion risk in
      patients with hemoglobin > 10 to < or = 13 g/dL. Baseline hemoglobin
      concentration is an excellent predictor of transfusion risk in orthopedic
      surgical patients. As a result, hemoglobin testing should be considered a part of
      routine preoperative testing for orthopedic surgical patients.

PMID- 9927115
TI  - Blood loss and transfusion rate in noncemented and cemented/hybrid total hip
      arthroplasty. Is there a difference? A comparison of 25 matched pairs.
AB  - A common assumption among orthopedic surgeons is that cemented/hybrid total hip
      arthroplasty (THA) results in lower transfusion requirements than noncemented
      THA. The hypothesized mechanism to account for transfusion differences is that
      cement application, after polymerization, decreases perioperative blood loss. To
      evaluate this theory, a retrospective matched-pair study was performed to
      quantify perioperative, intraoperative, postoperative blood loss, and transfusion
      requirements among patients undergoing cemented/hybrid and noncemented THA.
      Twenty-five THA procedures were either cemented or hybrid and 25 were
      noncemented. Patients were matched with respect to age, gender, weight, and
      diagnosis. Six patients in the noncemented group and 10 in the cemented/hybrid
      group received autologous blood in the Post Anesthesia Care Unit. Among this
      subgroup, those in the cemented/hybrid group received a significantly greater
      volume of transfused blood (519.20 mL, versus 291.67 mL in the noncemented group,
      P < .017). After stratifying patients by gender, additional analysis revealed a
      greater total blood loss in the male population than in females (1848 mL versus
      1464 mL, P < .004). Males also had a greater drain volume (548 mL versus 414 mL,
      P < .02). The female population utilizing hormone replacement therapy (HRT) was
      found to have a lesser blood loss (810 mL versus 1209 mL, P < .0107) and received
      a smaller amount of transfused blood (1164 mL versus 1377 mL) than those who were
      not on HRT. Other significant findings included a shorter length of stay in the
      cemented/hybrid group (6.85 versus 7.56 days, P < .012). Based on this matched
      pair retrospective analysis of blood requirements, there is no indication that
      cemented/hybrid and noncemented THA procedures result in different blood
      requirements. However, differences were found in several areas when the
      population was stratified by gender. The information obtained from this study is
      important in its ability to solidify a foundation from which blood management
      decisions can be made.

PMID- 9927116
TI  - Evolution of blood transfusion management for a busy knee practice.

PMID- 9927117
TI  - Blood management challenges in revision hip arthroplasty.

PMID- 9927118
TI  - Developments in blood management: the potential therapeutic role for epoetin alfa
      in orthopedic trauma.
AB  - Orthopedic trauma is a major source of morbidity and mortality in the United
      States and other countries. Major orthopedic trauma often results in significant
      blood loss, which is the most common cause of shock in the trauma setting.
      Transfusion of allogeneic blood and blood products may be used to maintain blood
      pressure but may not be the most effective therapy for the acute anemia that
      results from trauma-induced hemorrhage. Because acute anemia can interfere with
      successful and timely rehabilitation of these patients, it is important to be
      aggressive in treating anemia. One approach is to administer Epoetin alfa to
      stimulate erythropoiesis. A pilot study is currently in progress to test the
      efficacy of this approach in major trauma patients.

PMID- 9927119
TI  - Blood loss and transfusion management in spinal surgery.

PMID- 9927120
TI  - Recombinant human erythropoietin and blood management in pediatric spine surgery.

PMID- 9927121
TI  - Blood management challenges in orthopedic oncology.
AB  - Because anemia is associated with reduced long-term survival, and because
      allogeneic transfusion is linked to increased recurrence of disease and reduced
      rates of long-term survival, alternative options for managing anemia in the
      orthopedic oncologic patient have been sought. Managing the anemia of cancer is
      particularly challenging given the many obstacles to employing conventional blood
      management options. One potential means of treating perioperative anemia in
      orthopedic oncologic patients involves the use of Epoetin alfa. The clinical
      utility of Epoetin alfa in this setting, however, must be determined in
      controlled trials.

PMID- 9927122
TI  - Pulmonary function following laparoscopic or conventional colorectal resection: a
      randomized controlled evaluation.
AB  - BACKGROUND: Laparotomy causes a significant reduction of pulmonary function, and
      atelectasis and pneumonia occur after elective conventional colorectal
      resections. OBJECTIVE: To evaluate the hypothesis that pulmonary function is less
      restricted after laparoscopic than after conventional colorectal resection.
      DESIGN: A randomized clinical trial. SETTING: The surgical department of an
      academic medical center. PATIENTS: Sixty patients underwent laparoscopic (n = 30)
      or conventional (n = 30) resection of colorectal tumors. The 2 groups did not
      differ significantly in age, sex, localization or stage of tumor, or preoperative
      pulmonary function. MAIN OUTCOME MEASURES: Forced vital capacity, forced
      expiratory volume in 1 second, peak expiratory flow, mid-expiratory phase of
      forced expiratory flow, and oxygen saturation of arterial blood. RESULTS: The
      forced vital capacity (mean +/- SD values: conventional resection group, 1.73+/
      0.60 L; laparoscopic surgery group, 2.59+/-1.11 L; P<.01) and the forced
      expiratory volume in 1 second (conventional resection group, 1.19+/-0.51 L/s;
      laparoscopic surgery group, 1.80+/-0.80 L/s; P<.01) were more profoundly
      suppressed in the patients having conventional resection than in those having
      laparoscopic surgery. Similar results were found for the peak expiratory flow
      (conventional resection group, 2.51+/-1.37 L/s; laparoscopic resection group,
      3.60+/-2.22 L/s; P<.05) and the midexpiratory phase of forced expiratory flow
      (conventional resection group, 1.87+/-1.12 L/s; laparoscopic surgery group,
      2.67+/-1.76 L/s; P<.05). The oxygen saturation of arterial blood, measured while
      the patients were breathing room air, was lower after conventional than after
      laparoscopic resections (P<.01). The recovery of the forced vital capacity and
      forced expiratory volume in 1 second to 80% of the preoperative value took longer
      in patients having conventional resection than in those having laparoscopic
      resection (P<.01). Pneumonia developed in 2 patients having conventional
      resection, but no pulmonary infection occurred in the laparoscopic resection
      group (P>.05). CONCLUSIONS: Pulmonary function is better preserved after
      laparoscopic than after conventional colorectal resection. Pulmonary
      complications may be reduced after laparoscopic resections because of the better
      postoperative pulmonary function.

PMID- 9927123
TI  - Does the face protect the brain? A case-control study of traumatic brain injury
      and facial fractures.
AB  - BACKGROUND: The relationship between facial fractures and traumatic brain injury
      is controversial. Some studies show an increased risk of brain injury with the
      presence of facial fractures while others claim that facial fractures protect
      against brain injury. OBJECTIVE: To examine the association between facial
      fractures and traumatic brain injuries. DESIGN: Case-control study. SETTING:
      Subjects were recruited from the emergency departments of 7 hospitals in the
      Seattle, Wash, area. PATIENTS: Three thousand eight hundred forty-nine injured
      bicyclists and 5 scene deaths were identified from March 1, 1992, to August 31,
      1994, with complete data available on 3388 bicyclists. INTERVENTIONS: None.
      RESULTS: The study group was composed of 1602 cases with injuries to the head,
      face, or brain and 1540 control subjects. There were 203 bicyclists with
      traumatic brain injuries, of whom 62 had an identifiable intracranial injury and
      141 suffered a concussion. A total of 81 patients sustained facial fractures. The
      odds ratio for the risk of intracranial injury associated with facial fractures
      after adjustment for significant confounders was 9.9 (95% confidence interval,
      5.1-19.3). The effect was less strong but still present when all traumatic brain
      injuries including concussions were considered (odds ratio, 2; 95% confidence
      interval, 1.1-3.7). No association was found for concussion only. CONCLUSIONS:
      This study demonstrates no evidence that facial fractures help prevent traumatic
      brain injury. Data indicate that facial fractures are markers for increased risk
      of brain injury.

PMID- 9927124
TI  - Antireflux surgery enhances gastric emptying.
AB  - OBJECTIVE: To evaluate the influence of antireflux surgery on gastric emptying.
      DESIGN: Nonrandomized controlled trial 3 months before and after surgical
      intervention. SETTING: Secondary and tertiary referral center. PATIENTS AND
      CONTROL SUBJECTS: Twenty consecutive patients (7 women, 13 men), mean age 49.2
      years, with symptomatic, objectively confirmed gastroesophageal reflux disease
      and 10 healthy control subjects (3 women, 7 men), mean age 37.3 years.
      INTERVENTION: Laparoscopic or open Nissen fundoplication (in 1 case Toupet 180
      degrees posterior hemifundoplication). MAIN OUTCOME MEASURES: Gastric emptying
      scintigraphy, using solid food, in control subjects and patients 3 months before
      and 3 months after the operation; time to halving of the maximal activity and the
      activity remaining at 60, 100, and 120 minutes. RESULTS: Preoperative symptoms
      included pyrosis in 19 of 20 patients and regurgitation in 18. Three months
      postoperatively, 19 patients were symptom-free. The mean time to halving of the
      maximal activity decreased from 113 to 78 minutes (P = .001). Delayed gastric
      emptying was found postoperatively in 3 patients, compared with preoperative
      values, using activity at 60, 100, 120 minutes and the mean time to halving of
      the maximal activity as the variables. Compared with control subjects, gastric
      emptying was slower in patients preoperatively and faster postoperatively, but
      the difference was not statistically significant. CONCLUSION: Gastric emptying is
      enhanced after antireflux surgery, along with cessation of symptoms and healing
      of esophagitis.

PMID- 9927125
TI  - Primary common bile duct closure.
AB  - OBJECTIVE: To show that primary closure of the common bile duct following
      minicholecystectomy is safe and effective. DESIGN: Eighty-nine primary common
      bile duct closures done over 13 years. SETTING: General community hospital.
      PATIENTS: Patients with cholangiographic evidence of stones in the common bile
      duct. INTERVENTIONS: Minicholecystectomy followed by a primary common bile duct
      closure or common bile duct closure over a T tube. MAIN OUTCOME MEASURES:
      Successful clinical result of primary common bile duct closure following
      minicholecystectomy. RESULTS: Eighty-nine primary closures of the common bile
      duct between 1983 and 1986, resulting in successful clinical outcomes.
      CONCLUSION: Primary closure of the common bile duct following minicholecystectomy
      is safe, effective, and inexpensive.

PMID- 9927126
TI  - Effect of intraoperative blood transfusion on patient outcome in hepatic
      transplantation.
AB  - OBJECTIVE: To evaluate the effect of intraoperative transfusion of red blood
      cells (RBCs) on patient and graft survival. DESIGN: A retrospective study.
      SETTING: A tertiary care referral center. PATIENTS: Between January 1, 1992, and
      December 31, 1994, medical records from 225 adult patients who underwent primary
      liver transplantations were analyzed. RESULTS: Overall patient survival was 90%
      at 1 year and 86% at 3 years, while graft survival was 89% at 1 year and 85% at 3
      years. The following factors were associated with patient and graft survival:
      age, sex, medical condition at the time of transplantation, and intraoperative
      transfusion of RBCs. When these factors were subjected to a multivariate
      analysis, all were independently associated with survival. Fifty-four recipients
      (24%) underwent transplantation without intraoperative transfusion of RBCs, while
      171 recipients (76%) received at least 1 U of RBCs intraoperatively. Recipients
      who did not receive transfusion of RBCs had higher patient and graft survival
      rates than patients who did receive RBCs. By multivariate analysis,
      transplantation without intraoperative transfusion of RBCs no longer remained
      statistically significant, and only sex and the patient's medical condition were
      independently associated with patient and graft survival. Patient and graft
      survival decreased if 5 or more U were transfused, but transfusion of 5 or more U
      was not independently associated with survival by multivariate analysis.
      CONCLUSIONS: Increased transfusion requirement for RBCs was independently
      associated with patient and graft survival. While transplantation without
      transfusion of intraoperative RBCs was associated with superior patient and graft
      survival, these effects were overridden by patient sex and medical condition at
      the time of transplantation.

PMID- 9927127
TI  - The relationship between hospital volume and outcomes of hepatic resection for
      hepatocellular carcinoma.
AB  - BACKGROUND: Volume-outcome relations have been established for several complex
      therapies. However, few studies have examined volume-outcome relations for high
      risk procedures in general surgery, such as hepatectomy for hepatocellular
      carcinoma (HCC). OBJECTIVE: To evaluate the relation between hospital volume and
      outcome for patients undergoing hepatectomy for HCC. DESIGN: Retrospective cohort
      study. SETTING: All acute-care hospitals in California. PATIENTS: Hospital
      discharge data were analyzed for each patient in California who underwent major
      hepatic resection for HCC from January 1, 1990, through December 31, 1994.
      Hospitals were grouped according to number of hepatectomies performed at each
      center during the 5-year study. MAIN OUTCOME MEASURES: Outcome measures included
      operative mortality and length of hospital stay. Regression analyses were used to
      adjust for differences in patient mix. RESULTS: Five hundred seven patients
      underwent hepatectomy for HCC during the study. Hepatic resections were performed
      in 138 hospitals, with an overall in-hospital mortality rate of 14.8%. Three
      quarters of patients were treated at hospitals that average 3 or fewer hepatic
      resections for HCC per year. These low-volume providers represent 97.1% of all
      hospitals treating patients with HCC statewide. Significant reductions in risk
      adjusted operative mortality rates (22.7%-9.4%; P = .002, multiple logistic
      regression) and risk-adjusted length of stay (14.3-11.3 days; P = .03, multiple
      linear regression) were observed as hospital volume increased. CONCLUSIONS: Low
      operative mortality and length of stay were associated with high-volume centers.
      These data support regionalization of high-risk procedures in general surgery,
      such as hepatectomy for HCC.

PMID- 9927128
TI  - Preoperative serum albumin level as a predictor of operative mortality and
      morbidity: results from the National VA Surgical Risk Study.
AB  - OBJECTIVE: To improve the precision and reliability of estimates of the
      association between preoperative serum albumin concentration and surgical
      outcomes. DESIGN: Prospective observational study. Patients were followed up for
      30 days postoperatively. Multiple logistic regression models were developed to
      evaluate serum albumin level as a predictor of operative mortality and morbidity
      in relation to 61 other preoperative patient risk variables. SETTING: Forty-four
      tertiary care Veterans Affairs (VA) medical centers. PATIENTS: A total of 54215
      major noncardiac surgery cases from the National VA Surgical Risk Study. MAIN
      OUTCOME MEASURES: Thirty-day operative mortality and morbidity. RESULTS: A
      decrease in serum albumin from concentrations greater than 46 g/L to less than 21
      g/L was associated with an exponential increase in mortality rates from less than
      1% to 29% and in morbidity rates from 10% to 65%. In the regression models,
      albumin level was the strongest predictor of mortality and morbidity for surgery
      as a whole and within several subspecialties selected for further analysis.
      Albumin level was a better predictor of some types of morbidity, particularly
      sepsis and major infections, than other types. CONCLUSIONS: Serum albumin
      concentration is a better predictor of surgical outcomes than many other
      preoperative patient characteristics. It is a relatively low-cost test that
      should be used more frequently as a prognostic tool to detect malnutrition and
      risk of adverse surgical outcomes, particularly in populations in whom comorbid
      conditions are relatively frequent.

PMID- 9927129
TI  - Comparison of blue dye and probe-assisted intraoperative lymphatic mapping in
      melanoma to identify sentinel nodes in 100 lymphatic basins.
AB  - OBJECTIVE: To determine whether combining isosulfan blue dye with a
      radiopharmaceutical agent will increase intraoperative detection of sentinel
      nodes (SNs) in patients with early-stage melanoma. PATIENTS AND DESIGN: Clinical
      trial with a consecutive sample. Eighty-seven patients with clinical stage I
      melanoma underwent preoperative lymphoscintigraphy with 1 of 3
      radiopharmaceutical agents to identify the lymphatic basin and the site of the
      SN. All patients subsequently underwent intraoperative lymphatic mapping and
      selective lymph node dissection (SLND) with isosulfan blue dye and a
      radiopharmaceutical agent. A handheld gamma probe determined the radioactive
      counts over the draining lymph node basins and individual blue-stained lymph
      nodes before (in vivo) and after (ex vivo) their removal. An irrelevant body site
      was used as the denominator of a count ratio by which absolute counts were
      standardized for comparison. Completion lymphadenectomy was undertaken in
      patients whose SLND specimen had histopathologic evidence of tumor cells.
      SETTING: Tertiary care cancer center. INTERVENTION: Lymph node sampling. MAIN
      OUTCOME MEASURE: Accuracy of SN detection by blue dye and radiopharmaceutical
      techniques. RESULTS: Preoperative lymphoscintigraphic images identified 100 lymph
      node basins and 135 lymph nodes in 87 patients. All 3 radiopharmaceutical agents
      were equally effective in imaging the SN before surgery. During SLND, we
      identified and removed 136 blue-stained and radioactive (hot) SNs and 8
      additional non-blue-stained hot nodes from 98 basins (98.0%). Of the 144 excised
      lymph nodes, 132 nodes (91.7%) from 83 basins had either an in vivo- or an ex
      vivo-background count ratio of 2:1 or more and 125 nodes (86.8%) from 77 basins
      had a count ratio of 3:1 or more. Twelve blue-stained SNs had count ratios of
      less than 2:1. Seventeen SNs (11.8%) from 15 basins contained metastases: 16 were
      identified with blue dye and probe and 1 was identified with blue dye alone. Four
      (1.1%) of 377 non-SNs excised during completion lymphadenectomy contained
      metastases. There have been no lymph node recurrences during mean follow-up of
      16.3 months (range, 7-42 months). CONCLUSIONS: The blue dye technique remains the
      criterion standard for SLND in melanoma. The addition of a radiopharmaceutical
      tracer serves as a useful adjunct to the visualization of blue-stained SNs.

PMID- 9927130
TI  - Prognostic factors in T1 and T2 squamous cell carcinoma of the thoracic
      esophagus.
AB  - BACKGROUND: Prognostic indicators in patients with T2 tumor have not been fully
      understood. OBJECTIVE: To clarify the clinicopathologic characteristics and long
      term results of T1 and T2 squamous cell carcinomas of the thoracic esophagus.
      DESIGN: Consecutive case series. SETTING: Department of surgery in a university
      hospital. PATIENTS: Of 234 patients with primary squamous cell carcinoma of the
      thoracic esophagus, 142 patients underwent esophagectomy with curative intent: 97
      patients had pT1 and pT2 tumors. INTERVENTIONS: Investigated were
      clinicopathologic characteristics of 65 of 97 patients with pT1 and pT2 tumors;
      excluded were 7 patients who died of postoperative complications and another 25
      patients who died of causes other than esophageal cancer. MAIN OUTCOME MEASURES:
      Clinicopathologic characteristics and long-term results. RESULTS: Pathologic
      tumor stages were pT1 N0 in 23 patients, pT1 N(+) in 7 patients, pT2 N0 in 15
      patients, and pT2 N(+) in 20 patients. Fifty patients are alive and free of
      cancer and 15 patients died of tumor recurrence (1 patient with pT1 N0 tumor, 1
      patient with pT1 N[+][+] tumor, 1 patient with pT2 N0 tumor, and 12 patients with
      pT2 N[+] tumor). The sites of metastatic nodes in 6 survivors with pT1 N(+) tumor
      were a solitary perigastric node in 4 patients, a solitary mediastinal node in 1
      patient, and 2 mediastinal nodes in 1 patient. The 5-year survival rates of
      patients with pT1 N0, pT1 N(+), and pT2 N0 tumors all exceeded 85%, and the rate
      of those with pT2 N(+) tumor was 33.9% (pT2 N[+] vs. others: pT1 N0, pT1 N[+],
      and pT2 N0; P = .003). The factors affecting survival rate by univariate analysis
      were Borrmann classification (0, 1 vs. 2, 3, 4), tumor size (<4.0 vs. > or =4.0
      cm), combined T, N factor (pT2 N[+] vs. others), time of operation (< or =420 vs.
      >420 minutes), estimated blood loss (<1000 vs. > or =1000 mL), and lymph vessel
      invasion (marked vs. not marked). Stage pT2 N(+) tumor became a single
      independent prognostic factor for survival as determined by multivariate analysis
      (pT2 N[+] vs. others; P = .008). CONCLUSIONS: Stage pT1 N(+) tumors with a few
      diseased nodes and pT2 N0 tumors are considered to be a group with an excellent
      prognosis, similar to pT1 N0 tumors. Patients with pT2 N(+) diseases had worse
      prognoses and thus should have meticulous lymph node dissection and extensive
      adjuvant therapy.

PMID- 9927131
TI  - Lower esophageal sphincter dysfunction often precludes safe gastric feeding in
      stroke patients.
AB  - OBJECTIVES: To determine the relationship between stroke and lower esophageal
      dysfunction with vomiting and to identify an optimal nutrition protocol based on
      our findings. PATIENTS AND METHODS: The lower and upper esophageal sphincter
      functions were assessed in 35 patients who had an acute stroke to determine
      whether gastric or jejunal enteral feeding was the optimal route. Stroke was due
      to unilateral ischemia in 20 patients, unilateral intracerebral hemorrhage in 8
      patients, and global ischemia in 7 patients. Our study consisted of 18 men and 17
      women with an average age of 64 years. RESULTS: Using standard esophageal
      manometric definitions, the lower esophageal sphincter function was below normal
      in 24 patients: 3 had global anoxia, 5 had unilateral hemorrhage, and 16 had
      unilateral ischemia. The upper esophageal sphincter function was low in 30
      patients: 6 had global anoxia, 7 had unilateral hemorrhage, and 17 had unilateral
      ischemia. Based on lower esophageal sphincter pressure, 7 patients underwent tube
      gastrostomy and 13 patients underwent tube jejunostomy placement. All tolerated
      enteral alimentation well. Prior to lower esophageal sphincter assessment, 4
      patients had percutaneous endoscopy gastrostomy feedings that led to aspiration
      pneumonitis and consultation for tracheostomy; 2 terminally ill patients were
      referred to the ethics service, and 2 were converted to feeding via jejunostomy
      tube at the time of tracheostomy and did well. CONCLUSIONS: Vomiting with
      aspiration due to lower esophageal sphincter dysfunction is common after acute
      strokes. Esophageal manometry serves as a guide to find the optimal feeding
      route.

PMID- 9927132
TI  - Changes in respiratory mechanics after tracheostomy.
AB  - OBJECTIVE: To determine the effects of tracheostomy on respiratory mechanics and
      work of breathing (WOB). DESIGN: A before-and-after trial of 20 patients
      undergoing tracheostomy for repeated extubation failure. SETTING: Surgical
      intensive care unit at a university teaching hospital and a level I trauma
      center. PATIENTS: A consecutive sample of 20 patients who met extubation criteria
      (Pa(O2), >55 mm Hg; pH >7.30; and respiratory rate, <30/min on room air
      continuous positive airway pressure after 20 minutes) but failed extubation on 2
      occasions were eligible for the study. INTERVENTIONS: Respiratory mechanics, lung
      volumes, and WOB were measured before and after tracheostomy. MAIN OUTCOME
      MEASURES: Patients in whom extubation fails often progress to unassisted
      ventilation after tracheostomy. The study hypothesis was that tracheostomy would
      result in improved pulmonary function through changes in respiratory mechanics.
      RESULTS: Data are given as means +/- SDs. After tracheostomy, WOB per liter of
      ventilation (0.97+/-0.32 vs. 0.81+/-0.46 J/L; P<.09), WOB per minute (8.9+/-2.9
      vs. 6.6+/-1.4 J/min; P<.04), and airway resistance (9.4+/-4.1 vs. 6.3+/-4.5 cm
      H20/L per second; P<.07) were reduced compared with breathing via an endotracheal
      tube. These findings, however, do not fully explain the ability of patients to be
      liberated from mechanical ventilation after tracheostomy. In 4 patients who were
      extubated before tracheostomy, WOB was significantly greater during extubation
      than when breathing through an endotracheal or tracheostomy tube (1.2+/-0.19 vs.
      0.81+/-0.24 vs. 0.77+/-0.22 J/L). CONCLUSIONS: We believe that the rigid nature
      of the tracheostomy tube represents reduced imposed WOB compared with the longer,
      thermoliable endotracheal tube. The clinical significance of this effect is
      small, although as respiratory rate increases, the effects are magnified. In
      patients in whom extubation failed, WOB may be elevated because of incomplete
      control of the upper airway. Future studies should evaluate the cause of
      increased WOB after extubation.

PMID- 9927133
TI  - Resection with external beam and intraoperative radiotherapy for recurrent colon
      cancer.
AB  - OBJECTIVE: To review treatment outcomes for patients with locoregional recurrent
      colon cancer who underwent resection, intraoperative radiotherapy (IORT), and
      external beam radiotherapy (EBRT). DESIGN: Retrospective study of patients
      treated between January 1990 and June 1994. SETTING: Tertiary care cancer center.
      PATIENTS: Eleven patients with bulky recurrent colon cancer extending to adjacent
      organs or structures signed informed consent forms to receive IORT. INTERVENTION:
      Of 10 patients who underwent exploratory laparotomy, 5 had no metastatic disease
      and underwent resection, IORT, and EBRT. Complete resection was accomplished in 4
      patients. Doses of IORT ranged from 13 to 20 Gy depending on residual tumor
      burden; EBRT was typically delivered postoperatively to a dose of 45 Gy. MAIN
      OUTCOME MEASURES: Survival and locoregional tumor control. RESULTS: All 4
      patients who underwent complete resection, IORT, and EBRT are alive without
      locoregional recurrence 53 to 77 months after treatment. Of these, only 1 patient
      developed distant metastases. The fifth patient, who had gross residual tumor,
      developed local recurrence 5 months after IORT. One patient developed an IORT
      complication-ureteral fibrosis leading to ipsilateral nephrectomy. CONCLUSION:
      Long-term disease-free survival can be achieved in selected patients with bulky
      regional recurrence of colon cancer with complete tumor resection, IORT, and
      EBRT.

PMID- 9927134
TI  - Prospective evaluation of total parathyroidectomy and autotransplantation for the
      treatment of secondary hyperparathyroidism.
AB  - OBJECTIVE: To evaluate the clinical effectiveness of total parathyroidectomy with
      autotransplantation for the treatment of hyperparathyroidism and the recurrence
      rate of hyperparathyroidism after this procedure. DESIGN: A prospective study of
      total parathyroidectomy and autotransplantation in 19 consecutive patients with
      severe secondary (renal) hyperparathyroidism. SETTING: University hospital
      department of surgery. PATIENTS: Nineteen patients operated on for the treatment
      of secondary hyperparathyroidism between March 1993 and March 1996. Eighteen had
      been receiving longterm hemodialysis, and 1 had a functioning renal graft.
      INTERVENTION: Total parathyroidectomy and autotransplantation of excised
      parathyroid tissue into the brachioradialis muscle of the arm opposite that in
      which the arteriovenous fistula had been placed for dialysis. MAIN OUTCOME
      MEASURES: Clinical and biochemical improvement, morbidity, mortality, and
      recurrence rates of hyperparathyroidism after the procedure. RESULTS: The
      conditions of 13 (72%) of 18 patients followed up improved, and the clinical and
      laboratory variables indicating secondary hyperparathyroidism returned to normal.
      One patient died 50 days after surgery. In 2 patients (10%), mild
      hypoparathyroidism developed, and in 1 patient (5%), persistent
      hyperparathyroidism developed and required reoperation. In 2 patients (10%),
      recurrent hyperparathyroidism developed, and 1 (5%) required reoperation.
      CONCLUSIONS: Total parathyroidectomy with autotransplantation effectively
      relieves the symptoms of hyperparathyroidism, and the recurrence rate of
      hyperparathyroidism is low. Because all procedures used resulted in good control
      of clinical and biochemical variables, the method used for the surgical treatment
      of secondary hyperparathyroidism depends on the surgeon's preference.

PMID- 9927135
TI  - The value of acute-phase protein measurements after curative gastric cancer
      surgery.
AB  - OBJECTIVE: To determine whether acute-phase protein measurement provides
      clinically useful information about tumor recurrence. PATIENTS AND METHODS: Acute
      phase serum protein levels were measured at regular intervals in 43 patients who
      underwent curative gastrectomy for gastric cancer. At 12 months after surgery,
      patients were grouped according to the presence or absence of a C-reactive
      protein response, and were followed up for a minimum of 12 months or until death.
      RESULTS: There was a significant difference (P = .02) in a recurrence rate
      between patients with a C-reactive protein response (3 of 4 patients) and those
      without such a response (4 of 39 patients). Moreover, serum levels of C4 and
      alpha1-antitrypsin 12 months after surgery in patients who eventually recurred
      were significantly (P<.05) higher than those in a group without recurrence.
      CONCLUSION: An acute-phase protein response may be a predictive factor in the
      early stages of tumor recurrence. Acute-phase protein measurement provided
      clinically useful information about tumor recurrence after curative gastric
      cancer surgery.

PMID- 9927136
TI  - Impairment of cardiac performance by laparoscopy in patients receiving positive
      end-expiratory pressure.
AB  - BACKGROUND: The cardiopulmonary effects of the combination of abdominal and
      thoracic pressures in humans have not been well delineated. OBJECTIVE: To study
      the cardiopulmonary effects of 15 mm Hg of intra-abdominal pressure in the
      presence and absence of 10 cm H20 of positive end-expiratory pressure (PEEP).
      DESIGN: Prospective. SETTING: University hospital. METHODS: Nine patients
      undergoing laparoscopic cholecystectomy had pulmonary compliance, cardiac output,
      exhaled carbon dioxide, and preload (left ventricular end-diastolic volume)
      determined at 4 points while undergoing ventilation with (1) no PEEP before
      pneumoperitoneum; (2) 10 cm H20 of PEEP and no pneumoperitoneum; (3) no PEEP and
      15 mm Hg of pneumoperitoneum; and (4) 10 cm H20 of PEEP and 15 mm Hg of
      pneumoperitoneum. Preload and cardiac output were determined by means of
      transesophageal echocardiography. Pulmonary compliance and exhaled carbon dioxide
      were determined by an attachment to the end of the endotracheal tube. MAIN
      OUTCOME MEASURES: Preload, cardiac output, exhaled carbon dioxide, and pulmonary
      compliance. RESULTS: There was no significant change from baseline in preload,
      cardiac output, or pulmonary compliance when either PEEP or pneumoperitoneum was
      applied separately. However, there was a significant decrease in preload (P<.01),
      cardiac output (P = .01), and exhaled carbon dioxide (P =.04) when PEEP and
      pneumoperitoneum were applied together. Pulmonary compliance was not
      significantly affected at any of these points. CONCLUSIONS: There was a
      significant reduction in preload and cardiac output when there was intra
      abdominal pressure of 15 mm Hg in the presence of 10 cm H20 of PEEP. This
      combination of pressures may pose a contraindication to laparoscopic surgery.

PMID- 9927138
TI  - Perforation of the sigmoid colon due to geophagia.

PMID- 9927137
TI  - Relationship of systemic inflammatory response syndrome to organ dysfunction,
      length of stay, and mortality in critical surgical illness: effect of intensive
      care unit resuscitation.
AB  - BACKGROUND: A systemic proinflammatory response has been implicated in the
      pathogenesis of organ dysfunction. The effects of surgery, surgical stress,
      anesthesia, and subsequent intensive care unit (ICU) resuscitation may affect the
      components of the systemic inflammatory response syndrome (SIRS) score
      (temperature, heart rate, respiratory rate, and white blood cell count). Any SIRS
      scores calculated within 24 hours after surgery or at the onset of nonoperative
      resuscitation may overestimate the proinflammatory response itself, making
      quantitation of SIRS at that time potentially too sensitive. We hypothesized that
      SIRS attributable to ICU resuscitation can be quantitated, and that SIRS after
      the first day of therapy in the ICU correlates with several outcomes. METHODS:
      Prospective analysis of 2300 surgical ICU admissions during a 49-month period.
      Acute Physiology and Chronic Health Evaluation III (APACHE III) scores were
      recorded after 24 hours. Daily and cumulative multiple organ dysfunction scores
      (0-4 points for each of 6 organs, 24 points total) and SIRS scores (1 point for
      each parameter, 4 points total) were recorded. Defined end points were hospital
      mortality, days in the ICU, and organ dysfunction. RESULTS: On day 1, 49.4% of
      patients had SIRS (score > or =2), whereas 34.5% of patients who remained in the
      ICU had SIRS (score > or =2) on day 2 (P<.001). The SIRS score decreased by a
      mean of 0.8 points from day 1 to day 2, regardless of the type of admission. A
      SIRS score that decreased on day 2, in comparison with the score on day 1,
      resulted in less mortality than a unchanged or higher score on day 2 (11% vs. 18%
      vs. 22%, P<.001). Systemic inflammatory response scores were higher for
      nonsurvivors than survivors on each of the first 7 days in the ICU. The day 2
      SIRS score correlated well with the admission APACHE III score (P<.001) and all
      defined end points (all P<.001). The day 2 SIRS score also correlated with the
      day 2 multiple organ dysfunction score (P<.001). By multiple logistic regression,
      APACHE III (P<.001), day 2 SIRS score (P<.01) (but not day 1 SIRS score, P =
      .99), and day 2 multiple organ dysfunction score (P<.001) (but not day 1 multiple
      organ dysfunction score, P = .81) predicted mortality. CONCLUSIONS: Systemic
      inflammatory response syndrome attributable to surgery or surgical stress can be
      quantitated. Twenty-four hours of ICU resuscitation results in a decline in the
      SIRS score. The magnitude of the proinflammatory response on the second ICU day
      may be a useful predictor of outcome in critical surgical illness.

PMID- 9927139
TI  - Transection of the appendix: a seat belt injury.

PMID- 9927140
TI  - Surgery in the Netherlands.

PMID- 9927141
TI  - Laparoscopic splenectomy.

PMID- 9927142
TI  - Necessity is the mother of invention.

PMID- 9927143
TI  - Henry H. Smith's A system of operative surgery.

PMID- 9927144
TI  - Reduced plasma transforming growth factor-beta1 levels in patients with chronic
      hepatitis C after interferon-alpha therapy: association with regression of
      hepatic fibrosis.
AB  - BACKGROUND/AIM: Transforming growth factor-beta1 is involved in liver fibrosis.
      Our aim was to examine the association of plasma transforming growth factor-beta1
      levels with the degree of liver fibrosis. METHODS: We analyzed plasma
      transforming growth factor-beta1 levels in 43 patients with chronic hepatitis C
      treated with interferon-alpha using a transforming growth factor-beta1 ELISA. The
      content of transforming growth factor-beta1 in liver tissue obtained by needle
      biopsy (n=13) was also analyzed. The degree of liver fibrosis was assessed
      histologically and morphometrically. RESULTS: Plasma transforming growth factor
      beta1 levels were significantly correlated with transforming growth factor-beta1
      content in liver tissue (r=0.83, p<0.001), indicating that plasma levels
      correspond with tissue cytokine. Plasma transforming growth factor-beta1 levels
      in patients (8.1+/-1.1 ng/ml) before interferon-a therapy were significantly
      higher than in controls (1.9+/-0.3 ng/ml) (p<0.01). Plasma levels were
      significantly correlated with the degree of fibrosis (p<0.01). Plasma
      transforming growth factor-beta1 levels were significantly decreased in sustained
      responders (from 5.2+/-1.0 ng/ml to 2.9+/-0.7 ng/ml), relapsed patients (from
      9.8+/-2.0 ng/ml to 3.4+/-0.6 ng/ml), and nonresponders (from 9.3+/-2.1 ng/ml to
      3.9+/-0.9 ng/ml) at the end of therapy (p<0.05 for all comparisons). Significant
      regression of liver fibrosis after therapy was observed in both sustained
      responders and nonresponders (p<0.05 for both). CONCLUSIONS: These observations
      suggest that plasma transforming growth factor-beta1 levels appear to be
      associated with the degree of liver fibrosis.

PMID- 9927146
TI  - Decreased Na+-dependent taurocholate uptake and low expression of the sinusoidal
      Na+-taurocholate cotransporting protein (Ntcp) in livers of mdr2 P-glycoprotein
      deficient mice.
AB  - BACKGROUND/AIMS: Ntcp-mediated uptake of bile salts at the basolateral membrane
      of hepatocytes is required for maintenance of their enterohepatic circulation.
      Expression of Ntcp is reduced in various experimental models of cholestasis
      associated with increased plasma bile salt concentrations. Mdr2 P-glycoprotein
      deficient mice lack biliary phospholipids and cholesterol but show unchanged
      biliary bile salt secretion and increased bile flow. These mice are evidently not
      cholestatic, but plasma bile salt concentrations are markedly increased. The aim
      of this study was to investigate the role of Ntcp in the elevated bile salt
      levels in mdr2 P-glycoprotein-deficient (-/-) mice. METHODS: Plasma membranes
      were isolated from male wild-type (+/+) and mdr2 (-/-) mice for measurement of
      Na+-dependent taurocholate transport and assessment of Ntcp protein levels by
      Western blotting. Northern blot analysis and competitive reverse transcription
      polymerase chain reaction were used to determine hepatic Ntcp mRNA levels.
      RESULTS: Kinetic analysis showed a 2-fold decrease in the Vmax of Na+-dependent
      taurocholate transport, with an unaffected Km in (-/-) mice compared with (+/+)
      controls. Ntcp protein levels were 4-6-fold reduced in plasma membranes of (-/-)
      mice relative to sex-matched controls. Surprisingly, hepatic Ntcp mRNA levels
      were not significantly affected in the (-/-) mice. CONCLUSIONS: Elevated plasma
      bile salt levels in mdr2 P-glycoprotein-deficient mice in the absence of overt
      cholestasis are associated with reduced Ntcp expression and transport activity.
      This is due to posttranscriptional down-regulation of Ntcp.

PMID- 9927145
TI  - Should patients with early loss of serum HCV-RNA during alpha interferon therapy
      for chronic hepatitis C be treated for 6 or 12 months?
AB  - BACKGROUND/AIMS: Retrospective studies have suggested that early loss of serum
      HCV-RNA predicts sustained response to alpha-interferon treatment in chronic
      hepatitis C, but the optimal duration of therapy after loss of HCV-RNA is not
      known. The aims of this study were: a) to prospectively evaluate the
      effectiveness of HCV-RNA testing after 1 month of alpha-interferon treatment in
      the prediction of sustained response, and b) to compare the efficacy of 6 and 12
      months of therapy in patients with a negative serum HCV-RNA test after the first
      month of treatment. METHODS: One hundred and thirty patients were administered
      interferon alpha-2b at doses related to body weight (< or > or = 60 kg) and to
      HCV genotype: 5 or 8 MU tiw for type 1, and 3 or 5 MU tiw for genotypes non-1.
      Serum HCV-RNA testing was performed using in-house nested RT-PCR at month 1, at
      the end of treatment and 6 months afterwards. We considered sustained response to
      be the maintenance of normal alanine aminotransferase and negativity at serum HCV
      RNA testing until the end of follow-up. RESULTS: Sustained response was observed
      in 2/72 (2.8%) patients with detectable HCV-RNA after the initial month of
      therapy, in 8/30 (26.7%) patients with early loss of HCV-RNA treated for 6 months
      and in 20/28 (71.4%) patients treated for 12 months (p<0.01). CONCLUSIONS: Serum
      HCV-RNA detectability after the first month is strongly associated with a very
      poor chance of sustained response, and these cases should be offered other
      treatments. Patients with early loss of HCV-RNA should complete a 12-month
      treatment, which appeared more effective than a 6-month treatment.

PMID- 9927148
TI  - Evaluation of hepatocyte injury following partial ligation of the left portal
      vein.
AB  - BACKGROUND/AIMS: Total ligation of the left portal vein is thought to induce both
      hepatocyte apoptosis and necrosis. The pathological impact of partial ligation of
      a branch of the portal vein has not yet been evaluated. METHODS: We studied the
      degree of hepatocyte injury following 0, 43, 48, 59, 68, 72, 78 and 100% left
      portal vein stenosis in 200-g Sprague-Dawley male rats. Serum alanine
      aminotransferase levels, total body weight, and left and right liver lobe weights
      were measured at 2 and 7 days. Mitosis and 3H-thymidine labelling indices were
      measured as markers of proliferation; the apoptotic index and TUNEL stain were
      used as markers to measure apoptotic cell death. Necrosis was assessed
      morphologically. All these parameters were evaluated 2 days after ligation.
      RESULTS: There was a direct relation between the increase in weight of the right
      lobes and the reduction in weight of the left lobes. The degree of weight change
      correlated significantly with the degree of stenosis. In the right lobes, mitosis
      and 3H-thymidine labelling were increased in proportion to the degree of
      stenosis. In the left lobes, the decrease in volume of hepatocytes correlated
      with the degree of ligation, especially in the pericentral areas. Necrosis was
      identified only when ligation was > or = 68%, this being associated with an
      increase in alanine aminotransferase levels. On the other hand, apoptotic cells
      were identified in increasing numbers, starting from the lowest degree of
      ligation to 100% ligation. This was found both morphologically and with TUNEL
      stain. CONCLUSIONS: Partial ligation of the left portal vein induces left liver
      atrophy through hepatocyte volume loss and apoptosis. Necrosis is found only when
      the degree of ligation is severe.

PMID- 9927147
TI  - Active form of human hepatocyte growth factor is excreted into bile after
      hepatobiliary resection.
AB  - BACKGROUND/AIMS: We have shown that hepatocyte growth factor is excreted into
      bile after hepatectomy in patients with biliary tract carcinoma. However, it is
      not certain whether hepatocyte growth factor in bile is an active molecule or
      degradation products. METHODS: Bile was obtained from five patients after
      hepatobiliary resection. Bile hepatocyte growth factor was purified on a heparin
      Sepharose column and subjected to Western blotting. It was also tested for growth
      stimulating activity with rat primary cultured hepatocytes. Biles from 50
      patients who underwent various types of hepatobiliary resections were examined
      with respect to hepatocyte growth factor by an enzyme-linked immunosorbent assay.
      RESULTS: Upon Western blotting following nonreducing electrophoresis, the
      purified bile hepatocyte growth factor showed an 85 kDa peptide corresponding to
      native hepatocyte growth factor. Under reducing conditions, it showed bands of a
      subunit at 69 kDa and beta-subunit at 34 kDa with corresponding monoclonal
      antibodies. The purified bile hepatocyte growth factor stimulated the
      [3H]thymidine incorporation into primary cultured hepatocytes with a specific
      activity comparable to recombinant human hepatocyte growth factor. It was
      observed that the levels of bile hepatocyte growth factor increased after the
      various types of hepatobiliary resections, including bile duct resection without
      hepatectomy. CONCLUSIONS: The human bile obtained after hepatobiliary resection
      contains active hepatocyte growth factor that can stimulate hepatocyte growth.
      Bile hepatocyte growth factor increased not only in hepatectomy but in bile duct
      resection. These results suggest that the biliary tract system may play an
      important role in the production of bile hepatocyte growth factor.

PMID- 9927149
TI  - Differential expression of prostanoid receptors in hepatocytes, Kupffer cells,
      sinusoidal endothelial cells and stellate cells of rat liver.
AB  - BACKGROUND/AIMS: Prostanoids produced by nonparenchymal cells modulate the
      function of parenchymal and nonparenchymal liver cells during homeostasis and
      inflammation via eight classes of prostanoid receptors coupled to different G
      proteins. Prostanoid receptor expression in parenchymal and nonparenchymal cells
      was studied in order to get a better insight into the complex prostanoid-mediated
      intrahepatic signaling network. METHODS: RNA was isolated from freshly purified
      parenchymal and nonparenchymal rat liver cells and the mRNA level of all eight
      prostanoid receptor classes was determined by newly developed semiquantitative
      reverse transcription-polymerase chain reaction protocols. RESULTS: The mRNAs for
      the prostanoid receptors were differentially expressed. Hepatocytes were the only
      cell type which contained the mRNA of the Gq-linked prostaglandin F2alpha
      receptor; they were devoid of any mRNA for the Gs-linked prostanoid receptors.
      Kupffer cells possessed the largest amount of mRNA for the Gs-linked
      prostaglandin E2 receptor subtype 2. Endothelial cells expressed high levels of
      mRNA for the Gq-linked thromboxane receptor and medium levels of mRNA for the Gs
      linked prostacyclin receptor, while stellate cells had the highest levels of mRNA
      for the prostacyclin receptor. The mRNAs for the Gq-linked prostaglandin E2
      receptor subtype 1 and the Gi-linked prostaglandin E2 receptor subtype 3 were
      expressed in hepatocytes and all nonparenchymal cell types at similar high
      levels, whereas the mRNA of the Gs-linked prostaglandin D2 receptor was expressed
      in all nonparenchymal cells at very low levels. CONCLUSIONS: In hepatocytes the
      prostaglandin F2alpha receptor can mediate an increase in glucose output via an
      increase of intracellular InsP3 while cAMP-dependent glucose output can be
      inhibited via the subtype 3 prostaglandin E2 receptor. The subtype 2
      prostaglandin E2 receptor can restrain the inflammatory response of Kupffer cells
      via an increase in intracellular cAMP The thromboxane receptor and the
      prostacyclin receptor in sinusoidal endothelial and the prostacyclin receptor in
      stellate cells may be involved in the regulation of sinusoidal blood flow and
      filtration.

PMID- 9927150
TI  - Expression patterns of matrix metalloproteinases and their inhibitors in
      parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and
      TGF-beta1.
AB  - BACKGROUND/AIMS: Although matrix metalloproteinases (MMPs) and their specific
      inhibitors (TIMPs) play an essential role in liver injury associated with tissue
      remodeling, the cellular origin of MMPs/TMPs within the liver remains to be
      clarified. METHODS: Different liver cell populations were analysed with respect
      to their expression by reverse transcription-polymerase chain reaction, Northern
      blot analysis and zymography. RESULTS: MMP and TIMP coding transcripts were
      detectable in all liver cell types by reverse transcription-polymerase chain
      reaction; however, the cellular expression levels were markedly different as
      assessed by Northern blot analysis. Gelatinase-B was predominantly expressed in
      Kupffer cells, gelatinase-A in hepatic stellate cells and rat liver
      myofibroblasts and stromelysins-1, -2 as well as collagenase in hepatic stellate
      cells. Membrane type-1 MMP (MMP-14) was found in significant amounts in all liver
      cells. TIMP-1 coding m-RNAs were present mainly in hepatic stellate cells and rat
      liver myofibroblasts, TIMP-2 additionally in Kupffer cells, while TIMP-3
      expression was detectable only in hepatocytes. During in vitro activation of
      hepatic stellate cells, MMP expression was mostly downregulated, while TIMP
      expression was enhanced, thereby providing an explanation for matrix accumulation
      co-localised with these cells during chronic liver injury. In general, TNF-alpha
      stimulated both MMP and TIMP expression of hepatic stellate cells, while TGF
      beta1 induced TIMP expression only. CONCLUSIONS: Collectively these data
      demonstrate that all resident liver cells are involved in matrix degradation to
      some extent and that hepatic stellate cells play an important role in matrix
      breakdown in addition to matrix synthesis. The cytokine-specific regulation of
      MMP/TIMP expression in hepatic stellate cells suggests that the initial matrix
      breakdown following liver injury might be enhanced by TNF-alpha, while diminished
      matrix degradation during chronic tissue injury might be due to the action of TGF
      beta1 through TIMP induction.

PMID- 9927151
TI  - Nitric oxide mediates the lipopolysaccharide dependent upregulation of the heme
      oxygenase-1 gene expression in cultured rat Kupffer cells.
AB  - BACKGROUND/AIMS: Heme oxygenase catalyzes the rate-limiting enzymatic step of
      heme degradation. The inducible isoform of heme oxygenase, heme oxygenase-1, is
      expressed at a low level in most tissues and is upregulated by its substrate heme
      and various stress stimuli. Kupffer cells which represent the largest population
      of the body's tissue macrophages serve physiological functions in the defense
      against various pathogens such as lipopolysaccharide. The goal of the present
      study was to investigate the heme oxygenase-1 gene expression in Kupffer cells of
      rat liver and in isolated Kupffer cell cultures during treatment with
      lipopolysaccharide. METHODS: Cryostat sections of normal rat liver were
      investigated by immunofluorescence double-staining using specific antibodies for
      rat heme oxygenase-1 and ED2. Isolation and cell culture of Kupffer cells and
      primary hepatocytes from rat liver, as well as Northern and Western blot
      analysis, were performed with standard protocols. RESULTS: Heme oxygenase-1
      protein was highly expressed in large sinusoidal cells of normal rat liver, which
      were identified as Kupffer cells by staining with the macrophage surface marker
      ED2. By contrast, no expression of heme oxygenase-1 was detected in liver
      parenchymal cells. High expression of heme oxygenase-1 was also found in isolated
      Kupffer cells in culture by immunocytochemical staining as well as by Western and
      Northern blot analysis. After treatment of Kupffer cells cultures with
      lipopolysaccharide, heme oxygenase-1 was upregulated on the protein and mRNA
      level in a time- and dose-dependent manner. This increase in heme oxygenase-1
      expression by lipopolysaccharide was prevented by the nitric oxide inhibitor N(G)
      monomethyl-L-arginine which was reversed by an excess of L-arginine. Various
      nitric oxide donors up-regulated heme oxygenase-1 mRNA expression in Kupffer
      cells. CONCLUSIONS: The lipopolysaccharide-dependent upregulation of the heme
      oxygenase-1 gene which is highly expressed in Kupffer cells is mediated by a
      nitric oxide-dependent mechanism.

PMID- 9927152
TI  - Long-term administration of PGE1 increases liver fibrosis and collateral blood
      flow in bile-duct-ligated rats.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the effect of early and
      chronic administration of a prostaglandin E1 analogue (misoprostol) in the
      prevention of liver fibrosis and portal hypertension. METHODS: Liver fibrosis was
      induced by bile duct ligation. Controls had a sham operation. Bile-duct-ligated
      rats were divided into two groups: placebo (vehicle only) and misoprostol (10
      microg/d by gavage) for 4 weeks after surgery. Liver fibrosis was assessed by the
      area of fibrosis (image analysis), liver hydroxyproline content and serum
      hyaluronate. Systemic and splanchnic hemodynamics were evaluated including spleno
      renal shunt blood flow by the transit-time ultrasound technique. RESULTS: Mean
      arterial pressure was significantly lower in the misoprostol group (p<0.01).
      There was an unexpected increase in fibrosis parameters in the misoprostol group
      compared to the placebo group, e.g. area of fibrosis: 9.5+/-4.0 vs 15.0+/-8.1%
      (p<0.05). Spleno-renal shunt blood flow was significantly higher in the
      misoprostol group than in the placebo group (4.6+/-3.7 vs 2.2+/-2.0 ml/min,
      p<0.05) while portal pressure was unchanged. CONCLUSIONS: The early and chronic
      administration of misoprostol enhances porto-collateral circulation blood flow
      and the development of liver fibrosis in bile-duct-ligated rats.

PMID- 9927154
TI  - Differential expression of monocyte chemotactic protein-1 (MCP-1) in transforming
      rat hepatic stellate cells.
AB  - BACKGROUNDS/AIMS: Hepatic stellate cells and infiltrating leukocytes play a key
      role in the pathogenesis of liver fibrosis. The chronic phase of liver
      inflammation is characterized by immigrating mononuclear cells. To understand the
      underlying mechanisms responsible for the attraction of mononuclear cells in the
      pathogenesis of liver fibrosis, we investigated the inducible production of
      chemotactic activities in hepatic stellate cells. METHODS: Cultured hepatic
      stellate cells of different transformation grades and after in vitro
      transformation to myofibroblast-like cells were stimulated with tumor necrosis
      factor-a or bacterial lipopolysaccharide. Mononuclear cell attracting chemotactic
      activities were evaluated by chemotaxis assays, ELISA, and Northern blot
      analysis. RESULTS: We observed a transformation grade-dependent differential
      responsiveness of hepatic stellate cells and myofibroblast-like cells. Monocyte
      chemotactic protein-1 was inducible by tumor necrosis factor-alpha in non
      transformed hepatic stellate cells. In contrast, monocyte chemotactic protein-1
      was not inducible by bacterial lipopolysaccharide until the cells were fully
      transformed into myofibroblast-like cells. Despite a delayed onset, the bacterial
      lipopolysaccharide-inducible monocyte chemotactic protein-1 expression did not
      depend on an endogenous production of tumor necrosis factor-alpha. CONCLUSIONS:
      Our results indicate that the tumor necrosis factor-alpha and bacterial
      lipopolysaccharide-inducible production of chemokines plays a central role in the
      pathogenesis of liver fibrosis. These data suggest that when hepatic stellate
      cells have been transformed to a myofibroblast-like cells phenotype, e.g. by
      chronic injury, the cells become more sensitive to bacterial lipopolysaccharide,
      which may potentiate the production of chemotactic and fibrogenic mediators. A
      strong secretion of monocyte chemotactic protein-1 may contribute to the
      maintenance of an inflammatory infiltrate dominated by mononuclear cells.

PMID- 9927153
TI  - The role of TGFbeta1 in initiating hepatic stellate cell activation in vivo.
AB  - BACKGROUND/AIMS: The activation of hepatic stellate cells is a key initiating
      event in hepatic fibrogenesis. Although TGFbeta1 is a potent inducer of collagen
      alpha1(I) expression in vitro and elevated levels of TGFbeta1 are found in
      patients and experimental animals with hepatic fibrosis and cirrhosis, the role
      of increased TGFbeta1 in the initiation of hepatic stellate cell activation in
      vivo is unknown. We used two experimental approaches to study this relationship:
      1) Induction of an acute liver injury with carbon tetrachloride (CCl4) in normal
      and TGFbeta1-knockout (ko) mice, and 2) overexpression of TGFbeta1 in the liver
      of wild-type mice using a recombinant replication-deficient adenovirus encoding
      human TGFbeta1 (Ad-TGFbeta1). METHODS: TGFbeta1-ko mice (n=6) and normal mice
      (n=6) were injected once intraperitoneally (i.p.) with CCl4 (1 microl/g BW) or
      mineral oil. Wild-type mice (n=3) were injected intravenously with Ad-TGFbeta1
      (10(10) pfu) or a control virus expressing beta-galactosidase (Ad-LacZ, 10(10)
      pfu). Animals were sacrificed after 3 days and total liver RNA was prepared. The
      expression of collagen alpha1(I) mRNA normalized to GAPDH mRNA was measured by
      RNase protection assay, asmooth muscle actin (alpha-sma) protein expression was
      analyzed by Western blotting. The expression of TGFbeta1, TGFbeta2, and TGFbeta3
      mRNAs were determined semi-quantitatively with RT-PCR. RESULTS: The collagen
      alpha1(I) mRNA was increased 10-fold in CCl4-treated wild-type mice compared to
      the controls. This increase was reduced about 80% in the TGFbeta1-ko mice. The
      TGFbeta1 mRNA levels in the wild-type mice were proportional to the collagen
      alpha1(I) mRNA levels. a-sma, a marker of hepatic stellate cell activation, was
      expressed earlier and at a higher level in wild-type mice than TGFbeta-ko mice
      after CCl4 treatment. The Ad-TGFbeta1 infected mice had 14-fold higher hepatic
      TGFbeta protein levels and 15-fold higher collagen alpha1(I) mRNA levels than the
      Ad-LacZ-infected control mice. Collagen alpha1(I) mRNA levels were proportional
      to the transgenic TGFbeta1 mRNA levels, while the endogenous TGFbeta1 was only
      slightly higher than in the controls. TGFbeta2 and TGFbeta3 mRNA levels were
      elevated in CCl4-treated wild-type and TGFbeta1-ko mice and in Ad-TGFbeta1
      infected mice compared to the controls. CONCLUSIONS: Absence of TGFbeta1 inhibits
      hepatic collagen alpha1(I) mRNA and alpha-sma protein expression by the toxic
      stimulus CCl4, and targeted TGFbeta1 overexpression increases collagen alpha1(I)
      mRNA and alpha-sma protein levels in the liver in vivo. Other TGFbeta family
      members do not compensate for the TGFbeta1 deficiency. This indicates that
      TGFbeta1 accelerates, but is not absolutely required, for the activation of
      hepatic stellate cells.

PMID- 9927155
TI  - Early effects of total paracentesis and albumin infusion on muscle sympathetic
      nerve activity in cirrhotic patients with tense ascites.
AB  - BACKGROUND/AIMS: Cirrhotic patients with ascites are characterized by a marked
      activation of the sympathetic and the renin-angiotensin-aldosterone system. Total
      paracentesis is associated with a short-lived suppression of the renin
      angiotensin-aldosterone system. Little information exists as to whether this
      favourable effect is parallelled by sympathoinhibition. METHODS: In 16 Child C
      cirrhotic patients (age: 57.1+/-6.2 years, mean+/-SEM) with tense ascites we
      assessed the time course of the effects of total paracentesis followed by
      intravenous albumin (6-8 g/l of ascites) on beat-to-beat mean arterial pressure
      (Finapres), heart rate, plasma norepinephrine, epinephrine (high performance
      liquid chromatography) and muscle sympathetic nerve activity (microneurography,
      peroneal nerve). Measurements were obtained under baseline conditions, during
      staged removal of ascitic fluid (250 ml/min) and 24 h later. The patient remained
      supine throughout the study period. RESULTS: Total paracentesis (10.6+/-1.3 l)
      induced a decrease in mean arterial pressure (from 95.0+/-2.6 mmHg to 88.2+/-3.2
      mmHg, p<0.01), in heart rate (from 82.5+/-3.3 beats/min to 77.1+/-2.8 beats/min,
      p<0.01) and a reduction in plasma norepinephrine values (from 782+/-133 pg/ml to
      624+/-103 pg/ml, p<0.01), which were substantially maintained 24 h later. In
      eight patients muscle sympathetic nerve activity did not change during
      paracentesis (from 65+/-7.1 bursts/min to 65+/-7.4 bursts/min, p=NS), but a
      marked reduction was observed 24 h later (48.4+/-5.6 bursts/min, p<0.01).
      CONCLUSIONS: These data provide the first evidence that total paracentesis exerts
      an acute marked sympathoinhibitory effect. Whether this is a long-lasting
      phenomenon and to what extent plasma expansion with albumin contributes to this
      effects need to be further addressed.

PMID- 9927156
TI  - Adenovirus-mediated gene expression in the septal cells of cirrhotic rat livers.
AB  - BACKGROUND/AIMS: Liver cirrhosis is characterized by the formation of fibrous
      septa following hepatic necrosis and fibrosis, and finally progression to severe
      hepatic failure and/or hepatocellular carcinoma. To establish effective therapy
      for cirrhosis using a designed gene, we examined whether recombinant adenovirus
      vectors could transfer foreign genes into the septal cells of cirrhotic livers.
      METHODS: Rats with cirrhosis induced by 4-8 weeks treatment with carbon
      tetrachloride were intravenously infected with a recombinant adenovirus
      Adex1CALacZ bearing a bacterial lacZ gene. Expression of the transferred gene was
      determined by X-gal staining. The infectivity of the vectors in vitro was
      examined using slice cultures from the cirrhotic rat livers. RESULTS: In normal
      rat livers, almost all hepatocytes expressed beta-galactosidase from the
      recombinant adenovirus vectors. In rat liver fibrosis, the adenovirus-mediated
      gene transfer to hepatocytes is markedly reduced compared with normal rat liver.
      In cirrhosis, there is an even stronger reduction in the number of transduced
      hepatocytes. On the other hand, in vitro infection to the slice culture
      demonstrated that the cirrhotic hepatocytes still maintained adenovirus
      infectivity. Moreover, in the kidney, which is the second target organ of
      adenovirus, there was no difference in infectivity between normal and cirrhotic
      rats. CONCLUSION: The recombinant adenovirus intravenously transmitted the
      foreign gene to septal cells in extranodular fibrous septa, rather than to
      hepatocytes within small nodules. Therefore, septal cells in the cirrhotic liver
      should be targeted with the adenovirus vector for a successful in vivo
      therapeutic strategy.

PMID- 9927157
TI  - Endothelium-dependent blunted membrane potential responses to ATP-sensitive K+
      channel modulators in aortae from rats with cirrhosis.
AB  - BACKGROUND/AIMS: In vivo studies have shown that arterial vasodilation induced by
      synthetic openers of ATP-sensitive K+ (K(ATP)) channels is decreased in rats with
      cirrhosis. Since vasodilation induced by these substances is mediated by membrane
      potential hyperpolarization in arterial smooth muscle cells, membrane potential
      hyperpolarization in response to K(ATP) channel openers may be altered in
      cirrhotic smooth muscle cells. The aim of the present study was to investigate
      the effects of K(ATP) channel modulators (i.e. openers and blockers of these
      channels) on the membrane potential in smooth muscle cells in isolated aortae
      from cirrhotic and normal rats. The influence of endothelin-1 production by
      endothelial cells on smooth muscle cells membrane potential responses to K(ATP)
      channel modulators was also studied. METHODS: Cells were impaled in situ (in
      intact and endothelium-denuded aortae) with a microelectrode that was used to
      measure membrane potentials. K(ATP) channel openers were diazoxide or cromakalim;
      blockers were glibenclamide or tolbutamide. Bosentan (a mixed endothelin receptor
      antagonist) and exogenous endothelin-1 were also used. Preproendothelin-1 mRNA
      was assayed in aortae by RNase protection assay. Aortic wall endothelin-1
      concentration was measured by double antibody radioimmunoassay technique.
      RESULTS: As expected, in smooth muscle cells in intact normal aortae, K(ATP)
      channel openers induced membrane potential hyperpolarization and K(ATP) channel
      blockers membrane potential depolarization. In smooth muscle cells in intact
      cirrhotic aortae, K(ATP) channel openers and blockers did not significantly
      change the membrane potential. Endothelium removal or exposure of intact aortae
      to bosentan restored normal membrane potential responses to K(ATP) channel
      modulators in cirrhotic smooth muscle cells and did not alter the effects of
      these substances in normal smooth muscle cells. In endothelium-denuded aortae,
      exposure to exogenous endothelin-1 suppressed membrane potential responses to
      K(ATP) channel modulators. In intact aortae, the abundance of preproendothelin-1
      mRNA and endothelin-1 did not significantly differ between normal and cirrhotic
      rats. CONCLUSIONS: K(ATP) channel opener-induced membrane hyperpolarization and
      K(ATP) channel blocker-elicited membrane depolarization are blunted in smooth
      muscle cells in intact cirrhotic aortae. This blunting is due to the activation
      of the endothelin-1 pathway in the aortic wall, downstream to the endothelial
      production of endothelin-1.

PMID- 9927158
TI  - Hepatocyte-stimulated expression of hepatocyte growth factor (HGF) in cultured
      rat hepatic stellate cells.
AB  - BACKGROUND/AIMS: Hepatic stellate cells appear to be the main producers of
      hepatocyte growth factor of the normal liver. Insulin-like growth factors in
      doses over 20 ng/ml have been reported to stimulate hepatocyte growth factor
      production in cultured hepatic stellate cells. The aim of the present study was
      to investigate whether parenchymal cell conditioned medium had insulin-like
      growth factor-independent effects on hepatic stellate cells. METHODS: Primary rat
      hepatic stellate cells were cultured for 1-7 days. DNA synthesis was measured by
      3H-thymidine incorporation. Hepatocyte growth factor and transforming growth
      factor beta1 immunoreactivity was quantified by ELISA. Hepatocyte growth factor
      mRNA levels were determined with gel RNase protection assay. Parenchymal cell
      conditioned medium was obtained from hepatocytes cultured for 2 days in medium
      without added serum or hormones. RESULTS: Incubation of 1-7-day-old hepatic
      stellate cells for 2 days with parenchymal cell conditioned medium enhanced the
      medium content of hepatocyte growth factor. Parenchymal cell conditioned medium
      contained less than 5.0 ng/ml immunoreactive insulin-like growth factor-1 as
      measured by radio immunoassay. Parenchymal cell conditioned medium did not
      contain any insulin-like growth factor bioactivity measured as phosphorylation of
      type 1 insulin-like growth factor receptor beta subunit and a protein with a size
      consistent with that of insulin receptor substrate-1. The stimulatory effect of
      parenchymal cell conditioned medium on hepatocyte growth factor was time- and
      dose-dependent. The effects of a high dose of parenchymal cell conditioned medium
      (dilution 1:2 containing less than 2.5 ng/ml insulin-like growth factor-1) were
      additive to that of high doses (100 ng/ml) of insulin-like growth factor-1 or des
      (1-3) insulin-like growth factor-1, an analogue with low affinity to insulin-like
      growth factor binding proteins. Neither parenchymal cell conditioned medium nor
      insulin-like growth factor-1 enhanced transforming growth factor beta1
      immunoreactivity in the medium. Both parenchymal cell conditioned medium and
      insulin-like growth factor-1 stimulated DNA synthesis in hepatic stellate cells,
      confirming previous reports. CONCLUSIONS: The present results indicate that both
      insulin-like growth factor-1 and insulin-like growth factor-1-independent factors
      from hepatocytes can stimulate hepatocyte growth factor production by hepatic
      stellate cells. Therefore, insulin-like growth factor-1 and other hepatocyte
      derived factors may indirectly affect hepatocytes via a paracrine loop.

PMID- 9927159
TI  - Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small
      hepatocellular carcinoma: special reference to imaging diagnosis.
AB  - BACKGROUND/AIMS: Blood concentration levels of alpha-fetoprotein like the Lens
      culinaris agglutinin-reactive fraction (AFP-L3) are a useful marker for
      predicting the long-term prognosis of hepatocellular carcinoma. This study
      investigated the relationship between serum AFP-L3 and various imaging
      modalities. METHODS: Sixty-three patients with small hepatocellular carcinomas <
      or = 2 cm in diameter were studied. Serum AFP-L3 concentrations were measured by
      lectin-affinity electrophoresis coupled with antibody-affinity blotting and
      expressed as % AFP-L3 (the percent of AFP-L3 as total AFP). A clinical "cutoff
      level" of 10% was used in this study to indicate the presence of hepatocellular
      carcinoma. Selective hepatic intraarterial digital subtraction angiography (DSA),
      ultrasonographic angiography with carbon dioxide microbubbles (USAG), and
      computed tomography during arterial portography (CTAP) were performed to evaluate
      the hemodynamics of hepatic nodules. RESULTS: Fourteen (22.2%) of the 63 patients
      were positive for % AFP-L3. The % AFP-L3 levels (n=45, 4.4%) of patients with
      hypervascular tumors were significantly higher than those (n=15, 0.0%) of
      patients with isovascular or hypovascular tumors as determined by USAG
      (p=0.0061). The % AFP-L3 levels (n=53, 4.4%) of patients with a negative portal
      blood supply were significantly higher than the % AFP-L3 levels (n=7, 0.0%) of
      patients with a positive portal blood supply as determined by CTAP (p=0.0140).
      The % AFP-L3 levels of patients with tumors with a long doubling time (DT) were
      significantly lower than for patients with tumors with a short DT (p=0.0176).
      CONCLUSION: AFP-L3 is a positive indicator which may be more specific for small
      advanced hepatocellular carcinoma.

PMID- 9927160
TI  - Long-term follow-up after liver transplantation for autoimmune hepatitis:
      evidence of recurrence of primary disease.
AB  - BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long
      term results and the incidence of recurrence of primary disease are unknown.
      METHODS: In this retrospective study we reviewed the clinical course of 25
      patients transplanted for autoimmune hepatitis and followed for a mean of 5.3
      years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival
      rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute
      rejection was 50% (+/-10.2%), which was comparable to that of patients
      transplanted for primary biliary cirrhosis and primary sclerosing cholangitis.
      Autoantibodies persisted in 77% of patients, at a lower titer than before liver
      transplantation. Ten patients were excluded from the study of autoimmune
      hepatitis recurrence, one because of an early postoperative death and nine
      because of hepatitis C virus infection acquired before or after liver
      transplantation. In the remaining 15 patients, who were free of hepatitis C virus
      infection, 5-year patient and graft survivals were 100% and 87%, respectively.
      Despite triple immunosuppressive therapy, three patients (20%) developed chronic
      hepatitis with histological and serological features of autoimmune hepatitis in
      the absence of any other identifiable cause. The disease was severe in two
      patients, leading to graft failure and asymptomatic in another, despite marked
      histological abnormalities. In one of these three patients, autoimmune hepatitis
      recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing
      liver transplantation for autoimmune hepatitis have an excellent survival rate
      although severe primary disease may recur, suggesting the need for stronger post
      operative immunosuppressive therapy.

PMID- 9927161
TI  - Indocyanine green clearance reflects reperfusion injury following liver
      transplantation and is an early predictor of graft function.
AB  - BACKGROUND/AIMS: Primary graft dysfunction is difficult to predict. We have
      previously shown that indocyanine green clearance measured at 24 h following
      orthotopic liver transplantation predicts graft survival and outcome. We
      prospectively evaluated the use of indocyanine green clearance (with a cut-off
      value of 200 ml/min) as a marker of graft function following orthotopic liver
      transplantation and investigated its relationship with the markers of reperfusion
      injury during orthotopic liver transplantation. METHODS: In all patients
      indocyanine green clearance was measured at 24 h. Repeated blood samples were
      taken before, during the anhepatic and reperfusion phase and up to 12 h following
      orthotopic liver transplantation to measure the levels of neutrophil elastase and
      reactive oxygen intermediates. All patients studied had normal hepatic arterial
      pulse on Doppler-ultrasound post orthotopic liver transplantation. RESULTS: All
      patients with indocyanine green clearance >200 ml/min recovered following
      orthotopic liver transplantation and remained well up to 3 months of follow up.
      Four patients had an indocyanine green clearance <200 ml/min; three were re
      transplanted for graft failure within 3 days of the transplant, while one
      survived after prolonged intensive support and hospitalization. Indocyanine green
      clearance significantly correlated with reactive oxygen intermediates production
      and neutrophil elastase during orthotopic liver transplantation (r=-0.61, p<0.002
      and r=-0.66, p<0.0009, respectively). Indocyanine green clearance was also
      significantly correlated with alanine aminotransferase and prothrombin time at 24
      h post-transplantation (r=-0.35, p<0.02 and r=-0.4, p<0.0077, respectively).
      CONCLUSION: Indocyanine green reflects the degree of reperfusion injury and is a
      good early marker of primary graft function. Indocyanine green clearance over 200
      ml/min is associated with favorable outcome.

PMID- 9927162
TI  - Depletion of mitochondrial DNA associated with infantile cholestasis and
      progressive liver fibrosis.
AB  - Few cases of infantile liver disease associated with mitochondrial DNA (mtDNA)
      depletion have been reported. Most of the patients died before 1 year of age of
      severe liver failure. We describe a new case, a 28-month-old child, presenting
      with cholestasis at age 2 months, complicated by progressive portal and lobular
      liver fibrosis. Growth and psychomotor development are undisturbed. There is no
      clinical evidence of either myopathy or neurological involvement. Metabolic
      investigation in plasma revealed an abnormal oxido-reduction status after fasting
      and after carbohydrate-rich meals. Light microscopy performed on liver biopsies
      revealed steatosis, abnormal hepatocytes with an "oncocytic" appearance and
      extensive fibrosis. Electron microscopic investigation showed an increased number
      of mitochondria with rare or enlarged cristae. Biochemical studies of liver
      biopsies showed that the respiratory chain activities containing mtDNA-encoded
      subunits were severely decreased (complexes I, III and IV). In contrast, the
      complex II activity was normal and the citrate synthase activity was greatly
      increased. Southern blotting analysis revealed that the ratio of mtDNA to nuclear
      DNA in liver was only 15% and 20% of the mean control value at ages 12 and 21
      months, respectively. For this mtDNA depletion syndrome which is clinically
      expressed in the liver, a liver transplantation is discussed.

PMID- 9927164
TI  - Sclerosing hepatic carcinoma in non-cirrhotic liver resembling metastatic
      adenocarcinoma.

PMID- 9927163
TI  - Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy,
      lactic acidosis, and mitochondrial DNA depletion.
AB  - Zidovudine is known to be responsible for a mitochondrial myopathy with ragged
      red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis alone or
      associated with hepatic abnormalities has also been reported. A single report
      mentioned the concomitant occurrence of muscular and hepatic disturbances and
      lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues
      were not studied. A 57-year-old man with AIDS, who had been treated with
      zidovudine for 3 years, developed fatigue and weight loss. Serum creatine kinase
      and hepatic enzyme levels were high. Lactic acidosis was present. Liver biopsy
      showed diffuse macrovacuolar and microvacuolar steatosis. After withdrawal of
      zidovudine, creatine kinase, aspartate aminotransferase, and alanine
      aminotransferase levels normalised within 5 days, and lactacidaemia decreased.
      Acidosis persisted. The patient became confused and febrile and died 8 days after
      detection of high blood lactic acid. A muscle sample obtained at autopsy showed
      mitochondrial abnormalities with ragged-red fibres and lipid droplet
      accumulation. Southern blot analysis showed depletion of mitochondrial DNA,
      affecting skeletal muscle and liver tissue. No depletion was found in myocardium
      and kidney. This case emphasises that zidovudine treatment can induce
      mitochondrial multisystem disease, as revealed in our case by myopathy, liver
      steatosis and lactic acidosis.

PMID- 9927166
TI  - A consensus conference on prognostic studies in hepatology.

PMID- 9927165
TI  - Hepatocyte transplantation: emerging insights into mechanisms of liver
      repopulation and their relevance to potential therapies.

PMID- 9927167
TI  - The impact of HCV genotypes on seroreactivity against HCV antigens immobilized on
      the RIBA 3.0 SIA.

PMID- 9927168
TI  - Octreotide in the treatment of the hepatorenal syndrome in cirrhotic patients.

PMID- 9927169
TI  - Conserved features at the 5 end of Drosophila R2 retrotransposable elements:
      implications for transcription and translation.
AB  - R2 non-LTR retrotransposable elements insert site-specifically into the 28S
      ribosomal genes of insects. The sequence of the 5' end of full-length R2 elements
      from thirteen species of Drosophila were compared. Sequences within the 5'
      untranslated region (5' UTR) revealed little to suggest the presence of a
      promoter. Protein translation initiates within the 5' UTR and requires the
      bypassing of a highly conserved termination codon preceding the single R2 open
      reading frame. This bypassing probably involves a conserved RNA secondary
      structure which brings a potential initiation codon into close proximity to this
      termination codon. The most highly conserved sequence within the 5' UTR has
      properties similar to internal ribosomal entry sites. Based on these findings, we
      propose that R2elements are co-transcribed with the 28S gene and are translated
      as part of a large ribosomal subunit.

PMID- 9927170
TI  - Cloning of a family of serine protease genes from the cat flea Ctenocephalides
      felis.
AB  - Serine protease gene fragments approximately 480 nucleotides in length were
      amplified from Ctenocephalides felis larval and adult cDNA libraries using
      degenerate oligonucleotide PCR primers. Partial clones of thirty-eight distinct
      serine protease encoding sequences were isolated, and nineteen different full
      length cDNAs encoding mature serine proteases were subsequently cloned and
      sequenced. All of the mature proteases contained the histidine, aspartic acid and
      serine amino acids of the catalytic triad characteristic of serine proteases. The
      mature C. felis serine proteases had amino acid sequences that were at most 29
      53% identical to those known insect and arachnid serine proteases. Two of the C.
      felis gene sequences had similarity with the Drosophila melanogaster
      developmental genes snake and stubble. mRNA expression of selected serine
      protease genes was examined in different life stages, tissues, genders, and in
      response to bloodfeeding.

PMID- 9927171
TI  - Characterization of the soluble guanylyl cyclase beta-subunit gene in the
      mosquito Anopheles gambiae.
AB  - Genomic DNA corresponding to the soluble guanylyl cyclase beta-subunit (GCSbeta)
      gene was cloned and sequenced from Anopheles gambiae. The sequence was 8103 bp
      long and presumably included the entire coding region. The deduced amino acid
      sequence was 71% and 62% similar to previously known Drosophila and vertebrate
      GCSbeta, while the C-terminus of A. gambiae GCSbeta was shorter. Because of the
      conserved characteristics in each functional domain, the high G+C% in the third
      codon positions compared to the introns, the lack of internal stop codons, and
      the fact that we identified the gene from a cDNA, we conclude that this A.
      gambiae gene is functional. This is the first detailed description of a guanylyl
      cyclase gene structure (e.g. intron-exon boundaries). Interestingly, within the
      fifth intron we found high similarity to the flanking regions of the Pegasus-27
      transposable element and other noncoding regions of the A. gambiae genome.

PMID- 9927172
TI  - Comparative analysis of promoters for transient gene expression in cultured
      mosquito cells.
AB  - Three heterologous promoters (hsp70 and actin 5C from Drosophila melanogaster and
      IE1 from the immediate early gene of the Bombyx mori baculovirus) were assessed
      for their ability to drive transient luciferase expression in mosquito cells.
      Overall, the actin 5C promoter was considerably more effective at driving
      luciferase expression than either hsp70 or IE1 in cell lines derived from
      Anopheles, Aedes and Culex species. hsp70 functioned well when induced by heat
      shock and was also induced to a lesser extent by chemicals such as sodium
      arsenite. IE1 was also an effective initiator of transcription, particularly in
      two Anopheles cell lines, but generally it performed less well than the actin 5C
      promoter and was also outperformed by hsp70 in Anopheles gambiae cells.

PMID- 9927173
TI  - Four serine proteinases expressed in Manduca sexta haemocytes.
AB  - Several putative serine proteinases were detected in Manduca sexta larval plasma
      by labelling with radioactive diisopropyl fluorophosphate. To begin to identify
      and characterize such enzymes, a polymerase chain reaction was carried out using
      haemocyte cDNA as template and primers designed to amplify conserved sequences
      from serine proteinases. Four serine proteinase cDNA fragments were cloned. These
      were used as probes to screen an M. sexta larval haemocyte cDNA library to obtain
      full-length clones encoding haemocyte proteinases 1-4 (HP1, HP2, HP3 and HP4).
      HP1 and HP2 contain an aminoterminal 'clip' domain similar to those found in
      horseshoe crab clotting enzyme and clotting factor B and also in the Drosophila
      melanogaster proteinases snake and easter. HP3 and HP4 are most similar to
      proteinases from mammalian leucocytes. HP1 and HP2 are both present in plasma.
      HP1 is expressed in haemocytes (granular cells and oenocytoids) and not in fat
      body. HP2 is expressed in fat body and in granular haemocytes, plasmatocytes and
      oenocytoids. After injection of larvae with bacteria, the level of HP2 mRNA
      decreased in haemocytes and increased in fat body.

PMID- 9927174
TI  - Molecular cloning and expression of two hexamerin cDNAs from the mosquito, Aedes
      aegypti.
AB  - Fourth-instar larvae of Aedes aegypti synthesize two types of hexamerins,
      Hexamerin-1 (AaHex-1) and Hexamerin-2 (AaHex-2), whose subunits are distinguished
      by different methionine and aromatic amino acid contents. In early female pupae
      only the methionine-rich AaHex-1gamma subunit accumulates to two-fold higher
      levels than in males. To investigate the relationship between hexamerin structure
      and the roles of Hex-1 and Hex-2 during mosquito development and reproduction, we
      have cloned and sequenced cDNAs encoding the AaHex-2alpha, -2beta and AaHex
      1gamma subunits. Comparison with other insect hexamerins revealed that the Aedes
      Hex-1 and Hex-2 proteins belong, respectively, to the two hexamerin subfamilies
      previously defined for brachyceran Diptera. Probes specific for the Hex-2alpha
      and Hex-1gamma transcripts showed that expression of both genes follows the same
      developmental timetable. However, greater Hex-1gamma mRNA accumulation may
      contribute to the higher levels of Hex-1 gamma protein in early female pupae.

PMID- 9927175
TI  - Phylogenetic status of a fecundity-enhancing Wolbachia that does not induce
      thelytoky in Trichogramma.
AB  - Wolbachia are widespread bacteria which infect a number of species of insects and
      other arthropods. They manipulate the reproduction of their hosts at their own
      advantage. In Trichogramma species all Wolbachia known so far induce thelytoky
      and form a monophyletic group in the B subdivision of Wolbachia. Here we show
      that some strains of the arrhenotokous species Trichogramma bourarachae harbour
      Wolbachia symbionts that locate in the A subdivision, and which do not induce
      thelytoky. Although the symbiont of T. bourarachae is closely related to
      Wolbachia that induce cytoplasmic incompatibility in other insects, no
      cytoplasmic incompatibilities were found in crosses involving infected and
      uninfected strains. In T. bourarachae the presence of this Wolbachia is
      associated with a higher fecundity of strains. Our results strongly suggest that
      Wolbachia are involved in this increased fecundity. Theoretical models on the
      evolution of host-Wolbachia interaction predict that a reduced effect on
      reproduction can be selected for if cost of infection is reduced. The effect in
      T. bourarachae should illustrate this prediction.

PMID- 9927176
TI  - Structure and expression of tandemly duplicated xanthine dehydrogenase genes of
      the silkworm (Bombyx mori).
AB  - Xanthine dehydrogenase (XDH) is a molybdoenzyme which catalyses oxidation of
      xanthine and hypoxanthine to uric acid. We isolated genomic clones of silkworm
      (Bombyx mori) XDH genes (BmXDH1 and BmXDH2). The BmXDH2 gene is located upstream
      from the BmXDH1 gene and they show a tandemly duplicated structure. Both BmXDH
      genes were expressed in the fat body and Malpighian tubules, whereas only the
      BmXDH1 gene was expressed in the midgut. Phylogenetic analysis indicates that
      BmXDH gene duplication occurred after the divergence of the silkworm and dipteran
      species. Intron insertion site comparison shows that some introns were lost
      during insect XDH gene evolution.

PMID- 9927178
TI  - Mitochondrial DNA sequence variation among populations and host races of Lambdina
      fiscellaria (Gn.) (Lepidoptera: Geometridae).
AB  - The hemlock looper, Lambdina fiscellaria (Gn.), is a recurring major forest pest
      that is widely distributed in North America. Three subspecies (L. f. fiscellaria,
      L. f. lugubrosa (Hulst) and L. f. somniaria (Hulst)) have been recognized based
      on larval host or adult pheromone differences, but no consistent morphological
      differences have been reported. To clarify their taxonomic status, we surveyed
      mitochondrial DNA (mtDNA) sequence and restriction site variation in two protein
      coding genes, cytochrome oxidase I and II (COI and COII), in populations across
      the range of L. fiscellaria. In addition to variation in COI and COII, we found
      an intergenic spacer region of 20-23 bp located between the tRNA tyrosine gene
      and the start of COI. Of the 141 specimens of L. fiscellaria assayed, 137 were
      grouped into two distinct mtDNA lineages, one of which was disproportionately
      associated with eastern populations and one with western populations. However,
      single specimens and two populations in eastern Canada had mtDNA resembling that
      of western populations. Three divergent and rare haplotypes had basal affinities
      to the two common lineages. The two major lineages of L. fiscellaria were
      diverged by approximately 2% from each other, as well as from the mtDNA of two
      outgroup species, L. athasaria (Walker) and L. pellucidaria(G. & R.). The two
      outgroup species had essentially the same mtDNA and may be conspecific. We
      interpret the pattern of mtDNA variation within L. fiscellaria as indicating
      genetic polymorphism within a single species without clear subspecific divisions,
      rather than evidence of multiple cryptic species.

PMID- 9927177
TI  - Cloning and expression of a novel juvenile hormone-metabolizing epoxide hydrolase
      during larval-pupal metamorphosis of the cabbage looper, Trichoplusia ni.
AB  - A full-length cDNA encoding for a microsomal juvenile hormone (JH)-metabolizing
      epoxide hydrolase (TmEH-1) was isolated from a cDNA library constructed from fat
      body of last stadium (wandering) cabbage loopers, Trichoplusia ni, at the exact
      developmental time of maximum JH epoxide hydrolase activity. TmEH-1 was 1887 base
      pairs in length with a 1389 base pair open reading frame encoding 463 amino
      acids. Amino acid sequence analysis showed that TmEH-1 was most similar to and
      contained the exact catalytic triad (Asp-226, Glu-403 and His-430) found in
      microsomal epoxide hydrolases. TmEH-1-specific message was present along with JH
      III epoxide hydrolase activity in fat body in feeding (days 1 and 2) and
      wandering (day 3) larvae with the peak in message level preceding the peak in JH
      epoxide hydrolase activity by 1 day. When TmEH-1 was expressed in baculovirus
      infected Spodoptera frugiperda cells, a 46,000 molecular weight protein appeared
      on SDS-PAGE which corresponded to the predicted size coded by the TmEH-1 message
      and which was positively correlated with increases in JH III epoxide hydrolase
      activity above that of wild-type controls. In subcellular distribution studies,
      58% of the juvenile hormone III epoxide hydrolase activity was in the insoluble
      fractions. Baculovirus expressed TmEH-1 demonstrated a higher specific activity
      for JH III as compared to the general EH substrates, cis- and trans-stilbene
      oxide. Southern blot analyses suggested that multiple epoxide hydrolase genes are
      present in T. ni.

PMID- 9927179
TI  - Insect immunity: molecular cloning, expression, and characterization of cDNAs and
      genomic DNA encoding three isoforms of insect defensin in Aedes aegypti.
AB  - Aedes aegypti were immune activated by injection with bacteria, and the
      expression of insect defensins was measured over time. Northern analyses
      indicated that defensin transcriptional activity continued for at least 21 days
      after bacterial injection, and up to 10 days after saline inoculation. Mature
      defensin levels in the haemolymph reached approximately 45 microM at 24 h post
      inoculation. cDNAs encoding the preprodefensins of three previously described
      mature Ae. aegypti defensins were amplified by PCR, cloned and sequenced. Genomic
      clones were amplified using primers designed against the cDNA sequence. Sequence
      comparison indicates that there is significant inter- and intra-isoform
      variability in the signal peptide and prodefensin sequences of defensin genes.
      Preprodefensin sequences of isoforms A and B are very similar, consisting of a
      signal peptide region of twenty amino acids, a prodefensin region of thirty-eight
      amino acids and a forty amino acid mature peptide domain. The sequence encoding
      isoform C is significantly different, comprising a signal peptide region of
      twenty-three amino acids, a prodefensin region of thirty-six amino acids, and the
      mature protein domain of forty amino acids. Analysis of the genomic clones of
      each isoform revealed one intron spatially conserved in the prodefensin region of
      all sequences. The intron in isoforms A and B is 64 nt long, and except for a 4
      nt substitution in one clone, these intron sequences are identical. The intron in
      isoform C is 76 nt long and does not share significant identity with the intron
      sequences of isoforms A or B. The defensin gene mapped to chromosome 3, between
      two known loci, blt and LF168.

PMID- 9927180
TI  - Precise excision and transposition of piggyBac in pink bollworm embryos.
AB  - Transposable elements such as P, hobo, Hermes, mariner and Minos have been
      successfully harnessed as gene vectors to achieve the transformation of several
      dipteran species including Drosophila melanogaster, Ceratitis capitata and Aedes
      aegypti. Plasmid-based excision and transposition assays have been useful
      indicators of an element's ability to be mobilized in vivo and thus potentially
      serve as a transforming vector. We report that the transposable element piggyBac
      is capable of precise excision and transposition in the pink bollworm
      (Pectinophora gossypiella), a worldwide pest of cultivated cotton. Combined with
      a suitable marker gene, the piggyBac element may serve as a vector for germline
      transformation in this and (potentially) other lepidopteran species.

PMID- 9927181
TI  - Tissue tropism, transmission and expression of foreign genes in vivo in midgut
      symbionts of tsetse flies.
AB  - Tsetse flies (Diptera: Glossinidae) harbour three different symbiotic organisms
      in addition to the pathogenic African trypanosomes they transmit. The two gut
      associated symbionts (primary, P; secondary, S) are enteric and are nutritionally
      required, whereas the third microorganism Wolbachia (family Rickettsiaceae)
      affects the reproductive biology of the insects it infects. The bacteriome
      associated P-symbiont (Wigglesworthia glossinidia) displays a concordant
      phylogeny with its host tsetse species, whereas midgut S-symbionts characterized
      from distant tsetse have identical 16S rDNA sequences and therefore may either
      represent recent independent acquisitions or horizontal transfer between species.
      The S-symbionts have been cultured in vitro and a genetic transformation system
      has been developed. Here we report on their density and tissue tropism in
      different species (G. m. morsitans, G. p. palpalis, G. austeni and G.
      brevipalpis) and on their maternal route of transmission to tsetse progeny. Using
      a bacterium-specific PCR-assay, the S-symbionts were found primarily in the
      midgut, haemolymph, milk gland and in G. palpalis also in salivary glands of
      teneral flies. In older flies these infections were found to spread to other
      tissues including muscle, testes and fat body. The S-symbionts were transformed
      to express the marker gene product, Green Fluorescent Protein (GFP) in vitro.
      When the recombinant symbionts were introduced into the haemoceal of fertile
      female flies via intrathoracic microinjection, they were detected in the
      intrauterine progeny, indicating that haemolymph may provide a possible route for
      their transmission. The implications of these results for symbiont-host
      interactions and for transgenic strategies in tsetse are discussed.

PMID- 9927182
TI  - Invasion of one insect species, Adalia bipunctata, by two different male-killing
      bacteria.
AB  - Male-killing bacteria, which are inherited through the female line and kill male
      progeny only, are known from five different orders of insect. Our knowledge of
      the incidence of these elements has stemmed from discovery of their phenotype in
      different species. Our estimate of the frequency with which insects have been
      invaded by these elements therefore depends on each observation of the male
      killing phenotype within a species being associated with a single microorganism.
      We here record an example of a single insect species being infected with two
      taxonomically distinct male-killing bacteria. Western European populations of the
      two-spot ladybird, Adalia bipunctata, have previously been shown to bear a male
      killing Rickettsia. However, we here show that the majority of the male-killing
      lines tested from Central and Eastern Europe do not bear this bacterium. Rather,
      16S rDNA sequence analysis suggests male-killing is associated with a member of
      the genus Spiroplasma. We discuss this conclusion in relation to the evolutionary
      genetics of male-killing bacteria, and the evolution of male-killing behaviour in
      the eubacteria.

PMID- 9927183
TI  - Is the insect glutathione S-transferase I gene family intronless?
AB  - The genes coding for class I glutathione S-transferases in insects were believed
      to be intronless because the coding sequence was not interrupted by an intron.
      But sequences of the untranslated 5' end of transcripts revealed the presence of
      an intron in housefly and Drosophila genes suggesting that most insect GSTI genes
      are in fact interrupted.

PMID- 9927184
TI  - Induction of gene expression of antibacterial proteins by chitin oligomers in the
      silkworm, Bombyx mori.
AB  - Activation of antibacterial protein genes by various chitin oligomers (from dimer
      to hexamer) was investigated by Northern blot analysis using cDNAs encoding
      cecropin B, attacin and lebocin from Bombyx mori as probes. All chitin oligomers
      tested were found to strongly trigger expression of cecropin B, attacin and
      lebocin genes. Furthermore, gene expression triggered by chitin oligomers was
      confirmed to occur specifically in the fat body and haemocytes. These results
      suggest that chitin oligomers have the same characteristics as those of
      lipopolysaccharide (LPS) and peptidoglycan in triggering gene expression of
      insect antibacterial proteins.

PMID- 9927185
TI  - p53 inhibits entry into mitosis when DNA synthesis is blocked.
AB  - Human and mouse fibroblasts with normal p53 fail to enter mitosis when DNA
      synthesis is blocked by aphidicolin or hydroxyurea. Isogenic p53-null fibroblasts
      do enter mitosis with incompletely replicated DNA, revealing that p53 contributes
      to a checkpoint that ensures that mitosis does not occur until DNA synthesis is
      complete. When treated with N-(phosphonacetyl)-L-aspartate (PALA), which inhibits
      pyrimidine nucleotide synthesis, leading to synthesis of damaged DNA from highly
      unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA
      replication, but cells with wild-type p53 do not, revealing that p53 also
      mediates a checkpoint that monitors the quality of newly replicated DNA.

PMID- 9927186
TI  - Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic
      stress.
AB  - In the cellular response to genotoxic stress, cell cycle checkpoint and apoptosis
      are considered to be two of the major biological events in maintaining genomic
      stability. The tumor suppressor p53 has been shown to play critical roles in
      these stress-induced cellular responses at least in part through the activation
      of its down-stream genes, such as p21CIP1/WAF1, GADD45 and BAX. In addition, p53
      has been found to down-regulate the expression of BCL-2, which is able to block
      apoptosis induced by both p53-dependent and independent signaling events. In this
      report, we have found that increased expression of Bcl-2 protein in the human
      Burkitt's lymphoma WMN cell line suppressed apoptosis induced by different DNA
      damaging agents. The induction of p53-regulated genes including GADD45,
      p21CIP1/WAF1 and BAX by genotoxic stress was substantially reduced in cells
      expressing high levels of Bcl-2 protein. Furthermore, Bcl-2 protein was shown to
      specifically suppress the p53-mediated transactivation of p21CIP1/WAF1 and PG13
      CAT, which is a typical p53-binding-site reporter construct. Similarly, the
      inhibitory effect of Bcl-2 protein was seen in a GADD45 promoter reporter
      construct after treatment with methylmethane sulfonate or UV-radiation. These
      results indicate that in addition to its apoptosis-suppressing activity, Bcl-2
      protein is able to inhibit transactivation of p53-regulated genes, which function
      in multiple important cellular responses to genotoxic stress, including the
      control of cell cycle checkpoints, cell growth suppression and DNA repair.

PMID- 9927188
TI  - Cell cycle regulation of the double stranded RNA activated protein kinase, PKR.
AB  - The interferon (IFN)-induced, double stranded RNA (dsRNA)-activated
      serine/threonine kinase, PKR, is a potent negative regulator of cell growth when
      overexpressed in yeast or mammalian cells. To determine whether endogenous PKR
      plays a role in cell growth control, we have investigated the regulation of PKR
      levels and activity during the cell cycle in human glioblastoma T98G cells. The
      steady-state level of PKR mRNA in T98G cells was highest in growth arrested
      cells, dropped sharply within 3 h of serum stimulation then gradually increased
      as cells progressed through G1, reaching a plateau in early S phase. PKR protein
      level increased following serum stimulation reaching a peak at the G2+M boundary
      and declining thereafter. In contrast, PKR kinase activity exhibited two peaks,
      in early G1 and at the G1/S boundary, declining sharply in early S phase. Thus,
      the activity profile did not follow the protein profile indicating a tight
      regulation of PKR at the level of activity. In T98G cells expressing the
      catalytically inactive PKRK296R the dsRNA-induced activation of NF-kappaB and IRF
      1 was suppressed and the mutant cells exhibited resistance to stress induced
      apoptosis. Cell cycle distribution analysis showed that the mutant expressing
      cells exhibited longer G1 phase and fewer cells engaged in S phase. Furthermore,
      early passage mouse embryo fibroblasts derived from PKR knockout mice grew more
      slowly compared with the control cells. Taken together these results suggest that
      PKR may play a role in cell cycle progression.

PMID- 9927187
TI  - Regulation of cyclooxygenase-2 pathway by HER2 receptor.
AB  - Emerging lines of evidence suggest that in addition to growth factors, the
      process of colorectal tumorigenesis may also be driven by the upregulation of the
      inducible form of cyclooxygenase-2 (COX-2), an enzyme responsible for the
      conversion of arachidonic acid to PGEs. The present study was undertaken to
      investigate the expression and activation of the HER family members, and to
      explore the regulation of COX-2 expression by the HER2 pathway in human
      colorectal cancer cells. Here, we report that human colorectal cancer cell lines
      express abundant levels of HER2 and HER3 receptors, and are growth-stimulated by
      recombinant neu-differentiation factor-beta 1 (NDF). NDF-treatment of colorectal
      cancer cells was accompanied by increased tyrosine phosphorylation and
      heterodimerization of HER3 with HER2. In addition, we demonstrated that HER2 and
      HER3 receptors in colorectal cancer cells are constitutively phosphorylated on
      tyrosine residues and form heterodimeric complexes in the absence of exogenous
      NDF. Inhibition of HER2/HER3 signaling by an anti-HER3 mAb against the ligand
      binding site resulted in a decrease in the levels of constitutively activated
      HER2/ HER3 heterodimers, and the unexpected reduction of COX-2 expression.
      Activation of the HER2/HER3 pathway by NDF induced the activation of COX-2
      promoter, expression of COX-2 mRNA, COX-2 protein and accumulation of
      prostaglandin E2 in the culture medium. Finally, we demonstrated that NDF
      promotes the ability of colorectal cancer cells to survive in an extracellular
      matrix milieu, such as Matrigel, and also to invade through a 8 microm porous
      membrane. These biological activities of NDF and its stimulation of cell
      proliferation are blocked by a specific inhibitor of COX-2. Taken together, our
      findings provide the first biochemical evidence of a possible role of the COX-2
      pathway in the mitogenic action of NDF in colorectal cancer cells where it may be
      constitutively upregulated due to the autocrine/paracrine activation of HER2/
      HER3 heterodimers.

PMID- 9927189
TI  - The community effect in FGF-1 mediated tumor progression of a rat bladder
      carcinoma does not involve a direct paracrine signaling.
AB  - A community effect was found to occur between heterogeneous tumor cell
      populations leading to an overall increased tumorigenicity without a clonal
      dominance of the more tumorigenic clone. In the rat bladder carcinoma cell line
      NBT-II, this effect appears mediated by the Fibroblast Growth Factor-1 (FGF-1)
      through either a direct or an indirect signaling pathway. Neovascularization
      induced by FGF-1 was found not to be responsible for the community effect. The
      present study shows that the community effect does not involve a direct FGF-1
      signaling since tumor cells expressing a dominant-negative FGF receptor mutant
      were still responding to the highly tumorigenic FGF-1 expressing cells. Tumors
      arising from inoculates of the FGF-1 producing NBT-II cells mixed with non
      tumorigenic epithelial MDCK cells contain only the tumorigenic cells indicating
      that MDCK cells may exerce a helper effect for the growth of the tumor not
      dependant on their own growth. Therefore the helper function of MDCK cells must
      be distinguished from a community effect where the contribution of low
      tumorigenic cells not only provides an in vivo growth advantage to few highly
      tumorigenic cells but become themselves highly tumorigenic indicating that the
      community effect may require cell-cell specific cooperativity independent from an
      helper effect.

PMID- 9927190
TI  - Cloning and characterization of a novel gene encoding a putative transmembrane
      protein with altered expression in some human transformed and tumor-derived cell
      lines.
AB  - Identification and characterization of genes expressed in normal cells and
      decreased in their malignant counterparts is an important method for detecting
      candidate tumor suppressors. Using differential display of mRNAs from
      nontumorigenic infinite life span human fibroblast cell strain MSU-1.1 and an
      isogenic fibrosarcoma-derived cell line, 6A/SB1, which was derived from chemical
      carcinogen transformed MSU-1.1 cells, we identified a novel gene, ST7, showing
      sixfold lower expression in 6A/SB1 cells compared with parental MSU-1.1 cells.
      Molecular cloning of a near full-length cDNA revealed that the novel gene encodes
      a putative transmembrane protein composed of 859 amino acids: the 492 N-terminal
      amino acids including a fivefold cysteine-rich repeat of 40 amino acids
      homologous to the ligand binding repeat of the known low density lipoprotein
      receptor, a 24 hydrophobic amino acid stretch spanning the plasma membrane, and a
      C-terminal domain of 343 residues. ST7 is located on human chromosome 8, band
      q22.2-23.1, the same locus as the genes involved in acute myeloid leukemia and a
      locus of high polymorphism in cancer biopsies. The ST7 gene is widely expressed
      in normal human tissues and is particularly abundant in human heart and skeletal
      muscle. Northern analysis of 15 tumor cell lines derived from patients and 16
      cell lines established from tumors formed in athymic mice by MSU-1.1 cells
      transformed in culture by various methods showed that 16 of the 31 cell lines
      have low or undetectable levels of ST7 mRNA. Furthermore, Western blotting
      analysis using a specific anti-peptide antibody demonstrated that the level of
      ST7 protein is high in normal fibroblasts and low in 12 sarcoma-derived cell
      lines tested. Altered expression of ST7 appears to occur at both the
      transcriptional and post-transcriptional levels. These studies are a first step
      in characterizing a novel putative receptor protein, whose expression is
      downregulated in some malignantly transformed cells, and which may play an
      important role in the transformation process of these cells.

PMID- 9927191
TI  - Expression of BCR - ABL in M1 myeloid leukemia cells induces differentiation
      without arresting proliferation.
AB  - The mechanism leading to the expanding population of maturing myeloid cells which
      characterises chronic myeloid leukemia (CML) remains obscure. Because of its
      ability to mimic the proliferative and cell survival functions of hematopoietic
      growth factors, we hypothesized that the oncogene activated in CML, BCR-ABL,
      might also influence differentiation. To test this hypothesis, we examined the
      effects of expressing BCR-ABL on the myeloid differentiation of murine M1
      leukemic cells, which cease dividing and differentiate into macrophages in the
      presence of the cytokines leukemia inhibitory factor (LIF) or interleukin (IL)-6.
      We found that BCR-ABL induced macrophage differentiation in M1 cells, accompanied
      by increased expression of macrophage cell surface markers and the acquisition of
      phagocytic ability. interestingly, clones of M1 cells which expressed BCR-ABL
      remained in cell cycle and were refractory to the growth inhibition and apoptosis
      induced by IL-6 or LIF in parental M1 cells. These cells also expressed
      inappropriately high levels of c-MYC mRNA for their degree of differentiation,
      which may have been important in maintaining cellular proliferation. These data
      suggest that BCR-ABL can stimulate both differentiation and proliferation and
      that these characteristics may contribute to the phenotype observed in CML.

PMID- 9927192
TI  - Elf3 encodes a novel 200-kD beta-spectrin: role in liver development.
AB  - beta-spectrins are crucial for the maintenance of cell shape, the establishment
      of cell polarity, and the formation of distinct membrane domains. Our strategy
      for identifying genes important for hepatocyte polarity has been to utilize
      subtractive hybridization of early embryonic mouse cDNA liver libraries. As a
      result, we have cloned three isoforms of a novel beta-spectrin elf (embryonic
      liver beta-fodrin), and here we report the analysis of elf3, the longest isoform
      (8172 nt). ELF3 comprises 2154 residues with an overall similarity of 89.0% and
      95.3% to mouse beta-spectrin (betaSpIIsigma1) at the nucleotide and amino acid
      level, respectively. ELF3 is characterized by an actin-binding domain, a long
      repeat domain, and a short regulatory domain remarkable for the absence of a PH
      domain. Linkage analysis reveals that elf3 maps to mouse chromosome 11 between
      D11Bir6 and D11Xrf477, a different chromosomal locus from that of the other four
      spectrin genes. Northern blot analysis utilizing an elf3 3'-UTR probe
      demonstrates an abundant 9.0-kb transcript in brain, liver, and heart tissues.
      Western blot with a polyclonal antibody against ELF identifies a 200 kD protein
      in mouse liver, brain, kidney, and heart tissues. Immunohistochemical studies
      demonstrate ELF labeling of the basolateral or sinusoidal membranes surface as
      well as a granular cytoplasmic pattern in hepatocytes. Antisense studies
      utilizing cultured liver explants show a vital role of elf3 in hepatocyte
      differentiation and intrahepatic bile duct formation. The differential
      expression, tissue localization, and functional studies demonstrate the
      importance of elf3 in modulating interactions between various components of the
      cytoskeleton proteins controlling liver and bile duct development.

PMID- 9927193
TI  - Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ
      3/BCL-6 oncogene.
AB  - BTB/POZ-domain C2H2 zinc(Zn)-finger proteins are encoded by a subfamily of genes
      related to the Drosophila gap gene kruppel. To date, two such proteins, PLZF and
      LAZ-3/BCL-6, have been implicated in oncogenesis. We have now identified a new
      member of this gene subfamily which encodes a 62 kDa Zn-finger protein, termed
      LRF, with a BTB/POZ domain highly similar to that of PLZF. Both human and mouse
      LRF genes, which localized to syntenic chromosomal regions (19p13.3 and 10B5.3,
      respectively), were widely expressed in adult tissues and cell lines. At
      approximately 9.5-10.0 days of embryonic development, the mouse LRF gene was
      expressed in the limb buds, pharyngeal arches, tail bud, placenta and neural
      tube. The LRF protein associated in vivo with LAZ-3/BCL-6, but not with PLZF to
      which it was more related. Although the LRF, or LAZ-3/BCL-6, BTB/POZ domain could
      readily homodimerize, no heterodimerization was detected in vivo between the LRF
      and LAZ-3/BCL-6 BTB/POZ domains and interaction between full length LRF and LAZ
      3/BCL-6 required the presence of both the BTB/POZ domain and Zn-fingers in each
      partner protein. As expected from the above results, LRF and LAZ-3/BCL-6 also
      colocalized with each other in the nucleus. Taken together, our findings suggest
      that BTB/ POZ-domain Zn-finger proteins may function as homo and heterodimeric
      complexes whose formation, and hence the resultant effect on transcription of
      their downstream target genes, is determined by the levels and expression domains
      of a given partner protein.

PMID- 9927194
TI  - Differential regulation of mitogen-activated protein kinases by microtubule
      binding agents in human breast cancer cells.
AB  - Drug design targeted at microtubules has led to the advent of some potent anti
      cancer drugs. In the present study, we demonstrated that microtubule-binding
      agents (MBAs) taxol and colchicine induced immediate early gene (c-jun and ATF3)
      expression, cell cycle arrest, and apoptosis in the human breast cancer cell line
      MCF-7. To elucidate the signal transduction pathways that mediate such biological
      activities of MBAs, we studied the involvement of mitogen-activated protein (MAP)
      kinases. Treatment with taxol, colchicine, or other MBAs (vincristine,
      podophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1
      (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of
      the MBAs changed the activity of extracellular signal-regulated protein kinase 2
      (ERK2). Activation of JNK1 or p38 by MBAs occurred subsequent to the
      morphological changes in the microtubule cytoskeleton induced by these compounds.
      Furthermore, baccatine III and beta-lumicolchicine, inactive analogs of taxol and
      colchicine, respectively, did not activate JNKI or p38. These results suggest
      that interactions between microtubules and MBAs are essential for the activation
      of these kinases. Pretreatment with the antioxidants N-acetyl-L-cysteine (NAC),
      ascorbic acid or vitamin E, blocked H2O2- or doxorubicin-induced JNKI activity,
      but had no effect on JNKI activation by MBAs, excluding a role for oxidative
      stress. However, BAPTA/AM, a specific intracellular Ca2+ chelator, attenuated
      JNK1 activation by taxol but not by colchicine, and had no effect on microtubule
      changes induced by taxol. Thus, stabilization or depolymerization of microtubules
      may regulate JNK1 activity via distinct downstream signaling pathways. The
      differential activation of MAP kinases opens up a new avenue for addressing the
      mechanism of action of antimicrotubule drugs.

PMID- 9927195
TI  - Hypermethylation of the cell cycle inhibitor p15INK4b 3'-untranslated region
      interferes with its transcriptional regulation in primary lymphomas.
AB  - The cyclin-dependent kinase inhibitor p15INK4b has been shown to be involved in
      human and rodent tumors and seems to act as a tumor suppressor gene in
      hematological malignancies. Alterations of this gene in tumors include mainly
      homozygous deletions and hypermethylation of the CpG island in the promoter
      region. In this work, we describe a new area sensitive to methylation in the 3'
      untranslated region (UTR) of the murine p15INK4b gene. This region shows
      different levels of methylation depending on the tissues, being relatively highly
      methylated in brain and gut, and weakly methylated in liver, spleen or thymus.
      DNA methylation and expression is similar in both maternal and paternal alleles
      indicating no imprinting effect. Although methylation of the p15INK4b 3'-UTR is
      low in normal thymus, increased levels (up to 100%) of specific methylation in
      this region are found in up to 30% of radiation- or carcinogen-induced thymic
      lymphomas, correlating with decreased gene expression. Hypermethylation of the
      p15INK4b 3'-UTR frequently occurs in tumors with loss of heterozygosity (LOH) but
      without methylation of the promoter CpG island or intragenic mutations.
      Furthermore, in vitro CpG methylation of the 3'-UTR produces reduced levels of a
      luciferase reporter in cultured cells. Methylation of two CpG sites in a 120 bp
      region is sufficient to interfere with transcription of the reporter gene. These
      data suggest that although the levels of p15INK4b in normal tissues can be mainly
      determined by promoter regulatory elements, strong hypermethylation of the 3'-UTR
      can interfere with transcription. Thus, hypermethylation of the 3'-UTR may
      explain the lack of p15INK4b gene expression in a subset of tumors with no
      promoter methylation and could be a new alternative mechanism for tumor
      suppressor gene inactivation in tumorigenesis.

PMID- 9927196
TI  - Coordinated changes in cell cycle machinery occur during keratinocyte terminal
      differentiation.
AB  - Differentiation of cells is typically marked by a cessation of proliferation with
      a concurrent entrance into a distinct metabolic state marked by tissue specific
      gene expression. The mechanism by which the cell exits the cell cycle in this
      process is poorly understood. To determine the potential roles of the cell cycle
      machinery in the regulation of the terminal differentiation process of epidermal
      cells, we selected a well characterized in vitro model in which primary mouse
      keratinocytes are induced to differentiate in response to a raised calcium ion
      concentration in the medium. The withdrawal from the cell cycle correlates very
      well with a number of changes in the cell cycle machinery. Changes in the
      phosphorylation status of the Rb family of proteins occurs coordinately with an
      increased association of p21, p27 and p57 with cdk2. Furthermore, we find that
      inhibition of cdk2 activity is not sufficient to elicit changes that occur during
      keratinocyte differentiation. Finally, the previously described v-Ha-ras block of
      keratinocyte differentiation correlates with altered regulation of both cyclin D1
      and cdk2 suggesting that these genes may play a role in the Ha-ras transformation
      of a keratinocyte.

PMID- 9927197
TI  - Anti-apoptotic function of Rac in hematopoietic cells.
AB  - The small GTP-binding protein Rac plays a pivotal role in the regulation of
      diverse physiological events including reorganization of the actin cytoskeleton,
      cell cycle progression, and transformation. Here we show an anti-apoptotic effect
      of Rac in interleukin-3-dependent murine hematopoietic BaF3 cells. Activated
      Rac(G12V), when ectopically expressed in BaF3 cells, rendered the cells resistant
      to apoptosis upon interleukin-3 deprivation, while activated mutants of Rho and
      Cdc42 displayed no significant anti-apoptotic effect. In contrast to activated
      Ras, which also supports cell survival in the absence of interleukin-3, Rac
      required fetal bovine serum for the prevention of cell death. The involvement of
      phosphatidylinositol 3-kinase downstream of Rac was demonstrated by the
      inhibition of Rac-induced cell survival by wortmannin and LY294002 and the
      presence of phosphatidylinositol kinase activity in the Rac immunoprecipitate.
      Furthermore, the serine/threonine kinase Akt was stimulated by activated Rac and
      fetal bovine serum in a synergistic manner. Rac-induced Akt activation was
      mediated by phosphorylation of threonine-308 and serine-473. In addition to the
      phosphatidylinositol 3-kinase/Akt pathway, the p38 mitogen-activated protein
      kinase pathway was crucial for Rac-dependent survival, whereas p38 mitogen
      activated protein kinase nas not implicated in Ras-induced anti-apoptotic
      signaling. These findings provide evidence for the involvement of Rac in survival
      signaling of hematopoietic cells.

PMID- 9927198
TI  - WT1 expression induces features of renal epithelial differentiation in
      mesenchymal fibroblasts.
AB  - The WT1 tumor suppressor gene, implicated in hereditofamilial and sporadic Wilms'
      tumor, is required for normal renal development and is up-regulated during the
      mesenchymal-epithelial transition. NIH3T3 fibroblasts overexpressing WT1 were
      less proliferative, larger in size and more firmly attached to tissue culture
      plastic, suggesting an alteration of their state of differentiation. These cells
      were studied in vivo by subcutaneous injection into nude mice. The resulting
      tumors exhibited epithelioid histopathology and formed desmosome-like structures.
      Molecular analyses of these WT1 expressing fibroblasts grown in culture and in
      nude mice revealed significant alterations in the expression of many kidney
      epithelial markers. These studies indicate that WT1 expression can initiate
      features of a program of epithelial differentiation consistent with a prominent
      role for WT1 in the mesenchymal epithelial transition that occurs during renal
      development. Through this work we identified a number of novel target genes for
      the WT1 transcription factor, including uvomorulin, integrin alpha8 and perlecan,
      and suggest that WTI may activate the IGF-II gene, also implicated in the
      development of Wilms' tumor.

PMID- 9927199
TI  - Strict regulation of c-Raf kinase levels is required for early organogenesis of
      the vertebrate inner ear.
AB  - Regulation of organogenesis involves a dynamic balance of the mechanisms
      regulating cell division, differentiation and death. Here we have investigated
      the pattern of expression of c-Raf kinase in the inner ear during early
      developmental stages and the consequences of manipulating c-Raf levels by
      misexpression of c-raf viral vectors in organotypic cultures of otic vesicle
      explants. We found that otic vesicles expressed c-Raf and its level remained
      constant during embryonic days 2 and 3 (E2-E3). c-Raf activity was increased in
      response to insulin like growth factor-I (IGF-I) and the activation by IGF-I of
      the c-Raf kinase pathway was a requirement to turn on cell proliferation in the
      otic vesicle. Overexpression of c-raf in E2.5 explants increased the
      proliferative response to low serum and IGF-I and blocked differentiation induced
      by retinoic acid. The increase in c-Raf levels also prevented nerve growth factor
      (NGF)-dependent induction of programmed cell death. Consistent with these
      results, the expression of a dominant negative c-Raf mutant potentiated retinoic
      acid action and decreased the rate of cell proliferation. We conclude that a
      strict control of c-Raf levels is essential for the co-ordination of the
      biological processes that operate simultaneously during early inner ear
      development.

PMID- 9927200
TI  - Apoptosis-prone phenotype of human colon carcinoma cells with a high level
      amplification of the c-myc gene.
AB  - Although apoptosis can be induced by the enforced expression of exogenously
      introduced c-myc genes, it is not clear whether overexpression resulting from the
      amplification of the resident c-myc gene in tumor cells is sufficient to induce
      apoptosis. We have investigated the relationship between c-myc gene amplification
      and the propensity of tumor cells to undergo apoptosis, using the SW613-12A1 and
      SW613-B3 cell lines, which are representatives, respectively, of tumorigenic and
      non-tumorigenic clones isolated from the SW613-S human colon carcinoma cell line.
      Tumorigenic clones are characterized by a high level of amplification and
      expression of the c-myc gene, whereas cells of non-tumorigenic clones have a
      small number of copies and a lower level of expression of this gene. Analysis of
      c-myc mRNA level in cells cultured under low serum conditions indicated that the
      expression of the gene is tightly regulated by serum growth factors in non
      tumorigenic B3 cells, whereas it is poorly regulated in tumorigenic 12A1 cells,
      the level of mRNAs remaining relatively high in serum-starved 12A1 cells. Under
      these conditions, 12A1 cells showed clear evidence of apoptosis, whereas B3 cells
      were completely refractory to the induction of apoptosis. Moreover, the study of
      cell lines derived from non-tumorigenic apoptosis-resistant clones following the
      introduction by transfection of exogenous c-myc gene copies showed that they have
      acquired an apoptosisprone phenotype. Altogether, our results strongly suggest
      that deregulated c-myc expression due to high-level amplification confers an
      apoptosis-prone phenotype to tumor cells. The possible consequences of these
      observations for cancer therapy are discussed.

PMID- 9927201
TI  - Adenovirus early region 1A protein binds to mammalian SUG1-a regulatory component
      of the proteasome.
AB  - Adenovirus early region 1A (Ad E1A) is a multifunctional protein which is
      essential for adenovirus-mediated transformation and oncogenesis. Whilst E1A is
      generally considered to exert its influence on recipient cells through regulation
      of transcription it also increases the level of cellular p53 by increasing the
      protein half-life. With this in view, we have investigated the relationship of Ad
      E1A to the proteasome, which is normally responsible for degradation of p53. Here
      we have shown that both Ad5 and Ad12 E1A 12S and 13S proteins can be co
      immunoprecipitated with proteasomes and that the larger Ad12 E1A protein binds
      strongly to at least three components of the 26S but not 20S proteasome. One of
      these interacting species has been identified as mammalian SUGI, a proteasome
      regulatory component which also plays a role in the cell as a mediator of
      transcription. In vitro assays have demonstrated a direct interaction between
      Ad12 E1A 13S protein and mouse SUGI. Following infection of human cells with Ad5
      wt and Ad5 mutants with lesions in the E1A gene it has been shown that human SUG1
      can be co-immunoprecipitated with full-length E1A and with E1A carrying a
      deletion in conserved region 1 which is the region considered to be responsible
      for increased expression of p53. We have concluded therefore that Ad EIA binds
      strongly to SUGI but that this interaction is not responsible for inhibition of
      proteasome activity. This is consistent with the observation that purified Ad12
      E1A inhibits the activity of the purified 20S but not 26S proteasomes. We have
      also demonstrated that SUGI can be co-immunoprecipitated with SV40 T and
      therefore we suggest that this may represent a common interaction of transforming
      proteins of DNA tumour viruses.

PMID- 9927202
TI  - Analysis of cell cycle arrest in adipocyte differentiation.
AB  - Confluent 3T3-L1 preadipocytes differentiate to adipocytes in the presence of
      insulin, dexamethasone, and isobutylmethylxanthine (IDI). A transient increase of
      DNA synthesis is induced in 3T3-L1 cells 18 h after addition of IDI, followed by
      an arrest in the G1 phase of the cell cycle. Growth arrested cells express the
      proto-oncogene c-myc and the gene for the CCAAT/enhancer binding protein
      (C/EBPalpha) between day 2 and 5. While c-Myc is strongly implicated in cell
      proliferation, C/EBPalpha: is a differentiation-specific transcription factor
      with antiproliferative activity. Here we have characterized the cell cycle arrest
      in differentiating 3T3-L1 cells. Arrested cells express the Cdk inhibitors p21
      and p27, but, at the same time, show hyperphosphorylation of Rb and expression of
      the E2F-regulated thymidine kinase gene. The addition of new serum to arrested
      cells resulted in cyclin A expression and Cdk2 activity, but not in DNA
      synthesis. Simian virus 40 large tumor antigen (LTAg) is a potent mitogen. The
      mutant LTAg-K1, deficient in binding of pocket proteins and unable to induce DNA
      synthesis in serum-starved 3T3-L1 cells, efficiently induced DNA synthesis in
      differentiating 3T3-L1 cells. This indicates that pocket proteins are probably
      not involved in the control of the cell cycle arrest during 3T3-L1 cell
      differentiation. Our data suggest that the differentiation-specific cell cycle
      block in 3T3-L1 cells is resistant to high levels of c-Myc, inactivation of
      pocket proteins, upregulation of cyclin A levels, and Cdk2 activation, but can be
      abolished by a function of LTAg that is independent of binding to pocket
      proteins.

PMID- 9927203
TI  - The proto-oncogene Bc16 inhibits apoptotic cell death in differentiation-induced
      mouse myogenic cells.
AB  - The Bc16 gene is located at chromosomal band 3q27, a breakpoint for translocation
      that frequently occurs in B cell lymphomas. Bc16 has been found to be
      preferentially expressed in germinal center B cells, and expression of this gene
      has been shown to be essential for germinal center formation in vivo. The
      physiological function of Bc16 and its role in lymphomagenesis, however, are not
      yet known. Since significant expression of Bc16 has been demonstrated in skeletal
      muscle, we have utilized a differentiation-inducible mouse myogenic cell line,
      C2C12, to elucidate the function of the Bc16 gene product. Expression of Bc16
      mRNA was very low in growing myocytes, but was increased in differentiating
      myocytes cultured in serum-starved medium. Incubation of these cells with
      cytokines or chemicals that are known to block differentiation suppressed this
      increased Bc16 message abundance, indicating that Bc16 induction is related to
      the process of terminal differentiation in muscle cells. While a fraction of
      myocytes is known to undergo apoptosis after serum-starvation to induce
      differentiation, adenovirus-mediated overexpression of Bc16 enhanced the
      viability of the differentiating cells by preventing the apoptosis. High levels
      of Bc16 antisense mRNA expression induced substantial apoptosis during the
      differentiation of C2C12 cells, but this was effectively prevented by infection
      with adenovirus that expressed Bc16 sense mRNA. These results indicate that Bc16
      acts to prevent apoptotic cell death in differentiating myocytes. The
      deregulation of expression of this antiapoptotic gene may also contribute to the
      development of B cell lymphomas.

PMID- 9927204
TI  - Mutant p53 gain of function: differential effects of different p53 mutants on
      resistance of cultured cells to chemotherapy.
AB  - Many tumors overexpress mutant forms of p53. A growing number of studies suggest
      that the nature of a p53 mutation in a cell can impact upon cellular properties,
      clinical responses to therapy and prognosis of a tumor. To explore the cellular
      basis of these observations, experiments were designed to compare the properties
      of cells with and without p53 mutations within the same cell population. To that
      end, various tumor-derived human p53 mutants were introduced into p53-null H1299
      lung adenocarcinoma cells. Clonogenic survival assays revealed that cells
      overexpressing the p53His175 mutant, but not the p53His273 mutant, recover
      preferentially from etoposide treatment. Moreover, p53His175 as well as p53His179
      reduced substantially the rate of etoposide-induced apoptosis, whereas p53His273
      and p53Trp248 had a much milder protective effect. In contrast, p53His175 and
      p53His273 exerted very similar effects on the cellular response to cisplatin;
      both conferred increased resistance to low concentrations of the drug (2.5
      microg/ml), but did not protect at all against high concentrations (10
      microg/ml). Hence particular p53 mutants may confer upon tumor cells a selective
      survival advantage during chemotherapy. These findings define a new type of
      mutant p53 selective gain of function, which may compromise the efficacy of
      cancer chemotherapy.

PMID- 9927205
TI  - Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell
      death accompanied by down-regulation of BCL-2 and BCL-X(L).
AB  - The BCL-6 proto-oncogene encodes a 92- to 98-kDa transcriptional repressor
      containing the BTB/POZ domain at its N-terminal region and the zinc finger domain
      at its C-terminal region, respectively. In the present study, we examined the
      function of BCL-6 by using a recombinant adenovirus expressing BCL-6 (Ax1CA-BCL
      6) and the lacZ reporter gene (Ax1CA-lacZ). Viability of CV-1 and HeLa cells
      infected with Ax1CA-BCL-6 was markedly reduced due to apoptosis, suggesting that
      BCL-6-overexpression induces apoptosis in CV-1 and HeLa cells. FACS analysis
      revealed that BCL-6-overexpressing cells are accumulated not only at the sub-G1
      but also at G2/M phase. Induction of apoptosis by BCL-6 was preceded by down
      regulation of apoptosis repressors BCL-2 and BCL-X(L). These results suggest that
      BCL-6 induces apoptosis by regulating the expression of these apoptosis
      regulating genes.

PMID- 9927206
TI  - Taxol selectively blocks microtubule dependent NF-kappaB activation by phorbol
      ester via inhibition of IkappaBalpha phosphorylation and degradation.
AB  - Activation of the NF-kappa-B transcription factors has been shown to be directly
      influenced by changes in the microtubule cytoskeleton network. To better
      understand cytoskeletal regulation of NF-kappaB, experiments were performed to
      determine whether the microtubule (MT) stabilizing agent taxol could modulate NF
      kappaB activation in the presence of different NF-kappa-B inducers. Pretreatment
      of murine NIH3T3 and human 293 cells with 5 microM taxol resulted in complete
      inhibition of phorbol, 12-myristate, 13-acetate (PMA) mediated NF-kappaB
      activation, detected as the loss of DNA binding and reduced NF-kappaB dependent
      reporter gene activity. Furthermore, in COS-7 and NIH3T3 cells, PMA-induced
      Ikappa-Balpha turnover was dramatically reduced in taxol treated cells, mediated
      via the inhibition of IkappaBalpha phosphorylation. However, taxol did not
      prevent TNF-alpha induced Ikappa-Balpha phosphorylation, degradation, or NF
      kappaB activation, indicating that TNF-alpha acts through a microtubule
      independent pathway. In vitro kinase assays with PMA stimulated cell extracts
      demonstrated that taxol reduced protein kinase C activity by 30%, thus
      implicating the loss of PKC activity as a possible regulatory target of taxol
      mediated suppression of NF-kappa-B. Since PMA causes modulation of
      cytoarchitecture through PKC activation, microtubule integrity and cell
      morphology was analysed by indirect immunofluorescence. Both PMA and nocodazole,
      a MT depolymerizing agent, caused microtubule depolymerization, whereas TNF-alpha
      did not alter MT integrity; concomitant taxol treatment blocked both nocodazole
      and PMA induced depolymerization of MTs, as well as NF-kappaB induction, thus
      demonstrating a link between microtubule depolymerization and NF-kappaB
      activation. These observations illustrate a novel biological activity of taxol as
      a selective inhibitor of NF-kappa-B activity, suggesting a link between the state
      of microtubule integrity and gene regulation.

PMID- 9927207
TI  - Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF
      receptor 3 signaling.
AB  - The VEGFR3/FLT4 receptor, which is involved in vasculogenesis and angiogenesis,
      binds and phosphorylates SHC proteins on tyrosine residues. SHC contains two
      phosphotyrosine interaction domains: a PTB (Phosphotyrosine Binding) and a SH2
      (Src Homology 2) domain. Previous studies have shown that SHC proteins are
      phosphorylated on Y239/Y240 and Y313 (Y317 in humans) by tyrosine kinases such as
      the EGF and IL3 receptors. We have investigated which of the SHC tyrosine
      residues are targeted by the VEGFR3/ FLT4 kinase and the role of the SHC PTB and
      SH2 domains in this process. Our results show that Y239/ Y240 and Y313 are
      simultaneously phosphorylated by the kinase, creating GRB2 binding sites.
      Mutation of SHC PTB, but not SH2, domain interferes with the SHC phosphorylation
      by VEGFR3/FLT4. Soft agar assay experiments revealed that the VEGFR3/FLT4
      transforming capacity is increased by the mutation of Y239/Y240 to phenylalanines
      in SHC, suggesting that these two residues mediate an inhibitory signal for cell
      growth. Mutation of the two phosphorylation sites increases this effect,
      suggesting that they have a synergistic role.

PMID- 9927208
TI  - Functional interaction between a novel protein phosphatase 2A regulatory subunit,
      PR59, and the retinoblastoma-related p107 protein.
AB  - The proteins of the retinoblastoma family are potent inhibitors of cell cycle
      progression. It is well documented that their growth-inhibitory activity can be
      abolished by phosphorylation on serine and threonine residues by cyclin dependent
      kinases. In contrast, very little is known about the dephosphorylation of
      retinoblastoma-family proteins. We report here the isolation, by virtue of its
      ability to associate with p107, of a novel Protein Phosphatase 2A (PP2A)
      regulatory subunit, named PR59. PR59 shares sequence homology with a known
      regulatory subunit of PP2A, PR72, but differs from PR72 in its expression pattern
      and its functional properties. We show that PR59 co-immunoprecipitates with the
      PP2A catalytic subunit, indicating that PR59 is a genuine component of PP2A holo
      enzymes. In vivo, PR59 associates specifically with p107, but not with pRb.
      Elevated expression of PR59 results in dephosphorylation of p107, but not of pRb,
      and inhibits cell proliferation by causing cells to accumulate in G1. These data
      support a model in which the distinct PP2A regulatory subunits act to target the
      PP2A catalytic subunit to specific substrates and suggest a role for PP2A in
      regulation of p107.

PMID- 9927209
TI  - Activation of human O6-methylguanine-DNA methyltransferase gene by glucocorticoid
      hormone.
AB  - O6-methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein,
      removes the mutagenic DNA adduct O6-alkylguanine, which is synthesized both
      endogenously and after exposure to alkylnitrosamines and alkylating antitumor
      drugs such as 2-chloroethyl-N-nitrosourea (CNU). The MGMT gene is highly
      regulated in mammalian cells and its overexpression, observed in many types of
      tumor cells, is often associated with cellular resistance to CNU. Dexamethasone,
      a synthetic glucocorticoid hormone, was found to increase MGMT expression in HeLa
      S3 cells, concomitant with their increased resistance to CNU. Two putative
      glucocorticoid responsive elements (GREs) were identified in the human MGMT
      (hMGMT) promoter. Transient expression of the luciferase reporter gene driven by
      an hMGMT promoter fragment containing these GREs was activated by dexamethasone.
      DNase I footprinting assays demonstrated the binding of glucocorticoid receptor
      to these sequences. In vitro transcription experiment showed that these DNA
      sequences are functional in glucocorticoid receptor signal-mediated activation of
      transcription. These results suggest glucocorticoid-mediated induction of the
      MGMT gene contributes to high level expression of MGMT.

PMID- 9927210
TI  - Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in
      hormone-dependent and -independent breast cancer cell lines.
AB  - We have compared the DNase I hypersensitivity of the regulatory region of two
      estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and 
      independent breast carcinoma cell lines. This strategy allowed the identification
      of two important control regions, one in pS2 and the other in cathepsin D genes.
      In the hormone-dependent MCF7 cell line, within the pS2 gene 5'-flanking region,
      we detected two major DNase I hypersensitive sites, induced by estrogens and/or
      IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located -10.5 Kb
      from the CAP site, within a region that has not been cloned. The presence of
      these two DNase I hypersensitive sites correlates with pS2 expression.
      Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable
      chromatin structural changes over the pS2 regulatory region, suggesting that the
      two transduction-pathways converge to a unique chromatin target. In two cell
      lines that do not express pS2, MDA MB 231, a hormone-independent cell line that
      lacks the estrogen receptor alpha, and HE5, a cell line derived from MDA MB 231
      by transfection that expresses estrogen receptor alpha, there was only one
      hormone-independent DNase I hypersensitive site. This site, pS2-HS2, was located
      immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive
      sites were present in the 5'-flanking sequences of the cathepsin D gene, which is
      regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3,
      located at positions -2.3 Kb and -3.45 Kb, respectively, were both hormone
      independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA
      MB 231 cells, that express cathepsin D constitutively, we detected an additional
      strong hormone-independent DNase I hypersensitive site, catD-HS4, located at
      position -4.3 Kb. This region might control the constitutive over-expression of
      cathepsin D in hormone-independent breast cancer cells. All together, these data
      demonstrate that a local reorganization of the chromatin structure over pS2 and
      cathepsin D promoters accompanies the establishment of the hormone-independent
      phenotype of the cells.

PMID- 9927212
TI  - Restoration of transcriptional activity of p53 mutants in human tumour cells by
      intracellular expression of anti-p53 single chain Fv fragments.
AB  - We report here the production and the properties of single chain Fv fragments
      (scFvs) derived from the anti-p53 monoclonal antibodies PAb421 and 11D3. 11D3 is
      a newly generated monoclonal antibody which exhibits properties very comparable
      to those of PAb421. The scFvs PAb421 and 11D3 are able to stably associate with
      p53 and to restore the DNA binding activity of some p53 mutants in vitro. When
      expressed in p53 -/-human tumour cells, the scFv421 is essentially localized in
      the cytoplasm in the absence of p53, and in the nucleus when exogenous p53 is
      present. Thus, p53 is also able to stably associate with an anti-p53 scFv in
      cells. Cotransfection of p53 -/- human tumour cells with expression vectors
      encoding the His273 p53 mutant and either scFv leads to restoration of the p53
      mutant deficient transcriptional activity. These data demonstrate that, in human
      tumour cells, these scFvs are able to restore a function essential for the tumour
      suppressor activity of p53 and may represent a novel class of molecules for p53
      based cancer therapy.

PMID- 9927211
TI  - Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly
      clustered.
AB  - The inv(16) and related t(16;16) are found in 10% of all cases with de novo acute
      myeloid leukemia. In these rearrangements the core binding factor beta (CBFB)
      gene on 16q22 is fused to the smooth muscle myosin heavy chain gene (MYH11) on
      16p13. To gain insight into the mechanisms causing the inv(16) we have analysed
      24 genomic CBFB-MYH11 breakpoints. All breakpoints in CBFB are located in a 15-Kb
      intron. More than 50% of the sequenced 6.2 Kb of this intron consists of human
      repetitive elements. Twenty-one of the 24 breakpoints in MYH11 are located in a
      370-bp intron. The remaining three breakpoints in MYH11 are located more
      upstream. The localization of three breakpoints adjacent to a V(D)J recombinase
      signal sequence in MYH11 suggests a V(D)J recombinase-mediated rearrangement in
      these cases. V(D)J recombinase-associated characteristics (small nucleotide
      deletions and insertions of random nucleotides) were detected in six other cases.
      CBFB and MYH11 duplications were detected in four of six cases tested.

PMID- 9927213
TI  - A tumor specific single chain antibody dependent gene expression system.
AB  - The design of conditional gene expression systems restricted to given tissues or
      cellular types is an important issue of gene therapy. Systems based on the
      targeting of molecules characteristic of the pathological state of tissues would
      be of interest. We have developed a synthetic transcription factor by fusing a
      single chain antibody (scFv) directed against p53 with the bacterial tetracycline
      repressor as a DNA binding domain. This hybrid protein binds to p53 and can
      interact with a synthetic promoter containing tetracycline-operator sequences.
      Gene expression can now be specifically achieved in tumor cells harboring an
      endogenous mutant p53 but not in a wild-type p53 containing tumor cell line or in
      a non-transformed cell line. Thus, a functional transactivator centered on single
      chain antibodies can be expressed intracellularly and induce gene expression in a
      scFv-mediated specific manner. This novel class of transcriptional
      transactivators could be referred as 'trabodies' for transcription-activating
      antibodies. The trabodies technology could be useful to any cell type in which a
      disease related protein could be the target of specific antibodies.

PMID- 9927214
TI  - Syringe exchange and risk of infection with hepatitis B and C viruses.
AB  - The authors utilized a cohort study among Seattle injection drug users (IDUs) to
      assess whether participation in a syringe exchange program was associated with
      incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
      Susceptible IDU subjects (187 seronegative for antibody to HCV, and 460
      seronegative for core antibody to HBV) were identified in drug treatment,
      corrections, and social service agencies from June 1994 to January 1996, and
      followed for seroconversion one year later. The subjects included in the analysis
      were Seattle-King County (Washington State) area IDUs enrolled in a larger
      multipurpose cohort study, the Risk Activity Variables, Epidemiology, and Network
      Study (RAVEN Study). There were 39 HCV infections (20.9/100/year) and 46 HBV
      infections (10.0/100/year). There was no apparent protective effect of syringe
      exchange against HBV (former exchange users, relative risk (RR) = 0.68, 95%
      confidence interval (CI) 0.2-2.5; sporadic exchange users, RR = 2.4, 95% CI 0.9
      6.5; regular users, RR = 1.81, 95% CI 0.7-4.8; vs. RR = 1.0 for nonusers of the
      exchange; adjusted for daily drug injection). Neither did the exchange protect
      against HCV infection (sporadic users, RR = 2.6, 95% CI 0.8-8.5; regular users,
      RR = 1.3, 95% CI 0.8-2.2; vs. RR = 1.0 for nonusers; adjusted for recent onset of
      injection and syringe sharing prior to enrollment). While it is possible that
      uncontrolled confounding or other bias obscured a true beneficial impact of
      exchange use, these data suggest that no such benefit occurred during the period
      of the study.

PMID- 9927215
TI  - Invited commentary: needle exchange--no help for hepatitis?

PMID- 9927216
TI  - Physical activity in elderly subjects with impaired glucose tolerance and newly
      diagnosed diabetes mellitus.
AB  - The authors carried out a study to investigate the association between different
      indicators of physical activity and the prevalence of impaired glucose tolerance
      (IGT) and newly diagnosed diabetes (nDM) in a population-based cohort of elderly
      men and women in the Netherlands. A sample of participants of the Rotterdam Study
      (n = 1,016) aged 55-75 years who were not known to have diabetes mellitus
      underwent an oral glucose tolerance test. Physical activity was assessed by means
      of a self-administered questionnaire and expressed as time spent on activities
      per week. Associations with the prevalence of IGT and nDM were assessed by
      logistic regression analysis after adjustment for age, body mass index, waist-hip
      ratio, family history of diabetes, and smoking. A total of 745 subjects had
      normal glucose tolerance, 153 IGT, and 118 nDM. The total amount of time spent on
      physical activity decreased with increasing glucose intolerance. Adjusted for
      main confounders, vigorous activities such as bicycling (men: odds ratio (OR) =
      0.26, 95% confidence interval (CI) 0.14-0.49; women: OR = 0.37, 95% CI 0.18-0.78)
      and sports (men: OR = 0.28, 95% CI 0.11-0.74) showed an inverse association with
      the presence of nDM. For IGT, the associations pointed in the same direction but
      did not reach statistical significance. These results indicate that physical
      inactivity and glucose intolerance are associated among older adults similar to
      the way they are associated among middle-aged adults.

PMID- 9927217
TI  - Comparison of performance-based and self-rated functional capacity in Spanish
      elderly.
AB  - Recent data have shown differences between Spain and the United States in the
      prevalence of reported disability among community elderly. Differences in
      reporting functional capacity by culture may contribute to these observed
      differences. The purpose of this study was to estimate the agreement between self
      report of disability and performance-based measures for some basic mobility tasks
      in the community-dwelling elderly of a Mediterranean country. Interviews
      containing questions about difficulty for walking and rising from a chair, and
      performance-based measures (walking speed and chair stand tests) were carried out
      in 626 individuals aged 72 years and older in Barcelona, Spain. Kappa statistics
      were calculated, and logistic regression models were constructed to identify
      possible factors associated with under- and overreporting functional capacity.
      Moderate kappas (0.41-0.55) were found between self-report and performance-based
      measures. Patients who rated their health as "poor or very poor" were less likely
      to underreport disability (adjusted odds ratio (OR) = 0.2, 0.4) but more likely
      to overreport it (adjusted OR = 23.4, 9.9). No significant agreement differences
      by sex or informant source were found. These findings suggest that Spanish
      elderly self-report functional capacity accurately and that, contrary to previous
      results among US elderly, the direction of the observed disagreement is not
      systematic.

PMID- 9927219
TI  - Exposure to environmental and mainstream tobacco smoke and risk of spontaneous
      abortion.
AB  - The authors examined the risk of spontaneous abortion from environmental tobacco
      smoke (ETS) exposure in a prospective study of over 5,000 women conducted in
      California during 1990-1991. Among nonsmokers, there was little association by
      hours of ETS exposure at home or work (adjusted odds ratio (OR) for any exposure
      = 1.01, 95% confidence interval (CI) 0.80-1.27), or by paternal smoking. However,
      the risks associated with ETS exposure were increased among nonsmokers who had
      moderate alcohol or heavy caffeine consumption. A moderate association with
      maternal smoking was observed (adjusted OR for > or = 5 cigarettes per day = 1.3,
      95% CI 0.91-1.9).

PMID- 9927218
TI  - Use of simple measures of physical activity to predict stress fractures in young
      men undergoing a rigorous physical training program.
AB  - Among a population of randomly selected US Marine Corps recruits at Marine Corps
      Recruit Depot, San Diego, California, the authors developed a screening tool to
      identify individuals at high risk for lower extremity stress fracture when
      beginning a rigorous physical training program. The screening tool was developed
      among 1,286 recruits, then tested and refined among 1,078 additional recruits.
      The refined algorithm, consisting of five physical activity questions and a 1.5
      mi (2.4-km) run time, revealed that 21.6% of "high risk" subjects suffered more
      than three times as many stress fractures as "low risk" subjects. These data
      suggest that risk of stress fracture during rigorous physical training is
      increased by poor physical fitness and low levels of physical activity prior to
      their entry into the program.

PMID- 9927220
TI  - Oral clefts, transforming growth factor alpha gene variants, and maternal
      smoking: a population-based case-control study in Denmark, 1991-1994.
AB  - Studies in the United States have indicated that maternal first trimester smoking
      and infant transforming growth factor alpha (TGFA) locus mutations are associated
      with non-syndromic cleft lip and/or palate (CLP) and that a synergistic effect of
      these two risk factors occurs. Based on a Danish case-control study of CLP, the
      authors studied the effects of smoking and TGFA alleles in an ethnically
      homogeneous setting. Interview information was obtained for mothers of 302 CLP
      cases (96% of eligible) and for 567 mothers of nonmalformed children (94% of
      eligible). Multivariate logistic regression analyses revealed that smoking was
      associated with a moderately increased risk of cleft lip +/- cleft palate (CL(P))
      (odds ratio = 1.40, 95% confidence interval 0.99-2.00). No association between
      smoking and isolated cleft palate (CP) was observed. TGFA genotype was not
      associated with either CL(P) or CP, and no synergistic effect with smoking was
      observed. The "rare" TGFA allele occurred in 25% of both cases and controls
      compared with an average of 14% in other white control groups. Furthermore, the
      frequency of CLP in Scandinavia is among the highest in the world. Hence, it is
      possible that the previously reported association between TGFA and CLP to some
      degree can be attributable to confounding by ethnicity.

PMID- 9927221
TI  - Association between duration of obesity and risk of non-insulin-dependent
      diabetes mellitus. The Sotetsu Study.
AB  - The authors investigated the association between duration of obesity (ordinary
      obesity as body mass index (BMI) (kg/m2) > or = 25.0 and extreme obesity as BMI >
      or = 27.8) and the risk of diabetes mellitus. Male employees of a railway
      company, aged 30 years or older, observed for 10 years or more, free from serious
      disease conditions, with initial BMI <25.0, aged 30 years or more at the time
      diabetes was diagnosed, and with complete data, were examined by univariate and
      multivariate analyses (n = 1,598). Age-adjusted odds ratios for diabetes were
      significantly increased among males who were obese for 10-19.9 years and >20
      years (odds ratios = 2.10 and 2.84 for ordinary obesity and 6.14 and 4.15 for
      extreme obesity, respectively). Additional adjustment for current obesity,
      physical activity, smoking, drinking, family history, and observation period did
      not change the findings remarkably. In conclusion, > or = 10 years duration of
      ordinary obesity or > or = 1 year of extreme obesity was an important predictor
      for diabetes independent of age, current obesity, physical activity, smoking,
      drinking, family history, and observation period.

PMID- 9927222
TI  - Analytical and biologic variability in measures of hemostasis, fibrinolysis, and
      inflammation: assessment and implications for epidemiology.
AB  - An increasing number of cardiovascular epidemiologic studies are measuring non
      traditional risk markers of disease, most of which do not have established
      biovariability characteristics. When biovariability data have been reported, they
      usually represent a short time period, and, in any case, there is little
      consensus on how the information should be used. The authors performed a long
      term (6-month) repeated measures study on 26 healthy individuals, and, using a
      nested analysis of variance (ANOVA) approach, report on the analytical (CVA),
      intraindividual (CVI), and between individual (CVG) variability of 12
      procoagulant, fibrinolysis, and inflammation assays, including total cholesterol
      for comparison. The results suggest acceptable analytical variability (CVA < or =
      1/2 CVI) for all assays. However, there was a large range of intraindividual
      variation as a proportion of total variance (2-78%), and adjusting for
      intraindividual and between individual variation in bivariate correlations
      increased the observed correlation by more than 30 percent for three of these
      assays. Overall, the assays showed a significant increase in intraindividual
      variation over 6 months (p < 0.05). While these findings suggest that most of
      these assays have biovariability characteristics similar to cholesterol, there is
      variation among assays. Some assays may be better suited to epidemiologic
      studies, and knowledge of an assay's biovariability data may be useful in
      interpreting simple statistics, and in designing multivariate models.

PMID- 9927223
TI  - Parallel analyses of individual and ecologic data on residential radon,
      cofactors, and lung cancer in Sweden.
AB  - Divergent results from ecologic and analytic studies on residential radon and
      lung cancer have created uncertainty in terms of risk assessment. The authors
      performed concurrent analyses on individual and aggregated data from the
      nationwide case-control study of residential radon and lung cancer in Sweden. For
      data aggregated on the county level, the ecologic excess relative risk estimates
      per 100 Bqm(-3) residential radon concentration ranged from -0.03 (95% confidence
      interval (CI) -0.21 to 0.15) to 0.00 (95% CI -0.21 to 0.21) with different
      adjustment for cofactors. For individual-level data, the average within-county
      excess relative risk estimates ranged from 0.07 (95% CI -0.01 to 0.15) to 0.11
      (95% CI 0.01-0.27) with similar adjustment. Effect modification by differential
      county-level radon-smoking correlations appeared insufficient as an explanation
      for ecologic bias in the Swedish data. On the other hand, adjustment for latitude
      led to congruence between the two levels of analysis. The results confirm that
      ecologic studies may be misleading in studies of weak associations, even when
      major risk factors are accounted for. The large impact of latitude may be unique
      to Sweden and due to the correlation of latitude both with residential radon and
      other determinants of lung cancer risk.

PMID- 9927224
TI  - Are long-term hormone replacement therapy users different from short-term and
      never users?
AB  - The characteristics that differentiate long-term (> or = 10 years) hormone
      replacement therapy (HRT) users from short-term (<10 years) users and nonusers
      are not well documented. The epidemiology of long-term HRT use was investigated
      within a random sample survey of 703 women aged 50-80 years who were members of
      Group Health Cooperative (GHC) of Puget Sound. Women who had been menopausal for
      > or = 10 years comprised the study population. Long-term HRT users (29.4
      percent) were compared with short-term (28.1 percent) and never users (42.5
      percent). The authors examined the association between duration of HRT use and
      demographic characteristics, personal and family medical history, menopausal
      symptoms, information used in decision making, attitudes toward HRT, provider
      encouragement to use HRT, and GHC utilization. Compared with never users, the
      strongest correlates of long-term HRT use were having a hysterectomy before or
      after menopause, positive attitudes espousing the benefits of HRTs, and perceived
      provider encouragement to use HRT. Long-term HRT use was not associated with
      educational attainment, ethnicity, body mass index, health status, physical
      activity, or family medical history. Correlates commonly associated with HRT use,
      such as higher education, greater physical activity and functioning, and lower
      chronic disease comorbidity, did not significantly distinguish long-term from
      short-term users.

PMID- 9927225
TI  - Accuracy of ICD-9-CM codes in detecting community-acquired pneumococcal pneumonia
      for incidence and vaccine efficacy studies.
AB  - Studies have used medical record discharge data as coded by the International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to
      estimate pneumococcal pneumonia incidence and vaccine efficacy. However, the
      accuracy of coding data to identify laboratory-confirmed pneumococcal pneumonia
      is not known. With the use of information collected in Ohio for a community-based
      pneumonia incidence study, the authors calculated the sensitivities,
      specificities, positive predictive values (PPV), and negative predictive values
      (NPV) of specific codes for pneumococcal pneumonia among hospitalized patients
      with community-acquired pneumonia. Sensitivities of the most common ICD-9-CM
      codes listed in the first five positions for patients with laboratory-confirmed
      pneumococcal pneumonia were 58.3% (code 481.0, pneumococcal pneumonia), 20.4%
      (38.0, streptococcal septicemia), 19.2% (38.2, pneumococcal septicemia), 15.0%
      (518.81, respiratory failure), 14.2% (486.0, pneumonia, organism unspecified),
      and 11.3% (482.3, streptococcal pneumonia). Using the first five listed ICD-9-CM
      codes rather than just the first listed code increased sensitivity without
      causing substantial change in specificity, PPV, and NPV. Sensitivity, PPV, and
      NPV of individual and groups of codes varied with different case definitions of
      pneumococcal pneumonia. Incidence and vaccine efficacy studies with the ability
      to validate diagnoses by medical chart review can use a combination of many ICD-9
      CM codes to maximize sensitivity. However, without the ability to review medical
      charts, researchers must carefully decide which codes would best suit their
      studies.

PMID- 9927226
TI  - Re: Residual confounding.

PMID- 9927227
TI  - Re: "Male pesticide exposure and pregnancy outcome".

PMID- 9927228
TI  - Re: "Hormone replacement therapy and risk of hospitalization for venous
      thromboembolism: a population-based study in southern Europe".

PMID- 9927229
TI  - The role of selective cyclooxygenase isoforms in human intestinal smooth muscle
      cell stimulated prostanoid formation and proliferation.
AB  - Intestinal smooth muscle plays a major role in the repair of injured intestine
      and contributes to the prostanoid pool during intestinal inflammatory states.
      Cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to
      prostanoids exists in two isoforms, COX-1 and COX-2. The purpose of this study
      was to determine the relative contributions of COX-1 and COX-2 in the production
      of prostanoids by human intestinal smooth muscle (HISM) cells when stimulated by
      interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS). Furthermore the
      effects of specific COX-1 and COX-2 inhibitors on the proliferation of smooth
      muscle cells was also evaluated. Confluent monolayer cultures of HISM cells were
      incubated with IL-1beta or LPS for 0-24h while control cells received medium
      alone. PGE2 and PGI2 as 6-keto-PGF1alpha and LTB4 were measured by a specific
      radioimmunoassay. COX enzymes were evaluated by Western immunoblotting.
      Unstimulated and stimulated cells were exposed to the specific COX-1 inhibitor
      valerylsalicylic acid (VSA) and the COX-2 inhibitors NS-398 and SC-58125. The
      effects of serum on proliferation were then evaluated in the presence of each of
      the specific COX inhibitors by incorporation of 3H-thymidine into DNA. IL-1beta
      and LPS increased both PGE2 and 6-keto-PGF1alpha in a dose dependent fashion with
      enhanced production detected two hours following exposure. Neither stimulus
      stimulated LTB4 release. Immunoblot analysis using isoform-specific antibodies
      showed that both COX-1 and COX-2 were present constitutively. Furthermore, COX-1
      was upregulated by each inflammatory stimulus. In a separate set of experiments
      cells were pretreated with either the selective COX-1 inhibitor VSA or the
      selective COX-2 inhibitors NS-398 or SC-58125 prior to treatment with IL-1beta or
      LPS. The COX-1 and COX-2 inhibitors decreased both basal and IL-1beta and LPS
      stimulated prostanoid release. Spontaneous DNA synthesis was present and serum
      consistently increased proliferation. 3H-thymidine incorporation, stimulated by
      serum, was inhibited by both COX-1 and COX-2 inhibitors. This study suggests that
      the prostanoid response stimulated by proinflammatory agents of gut-derived
      smooth muscle cells appears to be mediated by both COX-1 and COX-2 enzymes.
      Proliferation of smooth muscles cells also appears to be influenced by both COX-1
      and COX-2.

PMID- 9927230
TI  - Perpetuation of inflammation associated with experimental arthritis: the role of
      macrophage activation by neutrophilic myeloperoxidase.
AB  - Rheumatoid arthritis (RA) is characterized by an abnormal cellular and cytokine
      infiltration of inflamed joints. This study addresses a previously unrecognized
      interaction between neutrophilic-myeloperoxidase (MPO) and macrophages (Mphi)
      which could explain the perpetuation of inflammation associated with RA. A
      monoarticular arthritis was induced in female Lewis rats by injection of
      streptococcal cell wall extracts (PG-APS). After swelling and erythema subsided,
      joints were re-injected with one of the following: porcine MPO or partially
      inactivated MPO (iMPO). Injection with either MPO or iMPO induced a 'flare' of
      experimental RA. Blocking the Mphi-mannose receptor by mannans, ablated
      exacerbation of disease. These results indicate that MPO or iMPO can play a
      pivotal role in the perpetuation but not initiation of this RA model.

PMID- 9927231
TI  - Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP
      interaction on human neutrophil apoptosis.
AB  - The current study was undertaken to evaluate the effects of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling
      interaction on human neutrophil apoptosis, either occurring spontaneously or
      induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a
      cAMP analog) and forskolin (an adenylate cyclase activator) are all able to
      suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used
      in combination with cAMP-elevating agents, an additive effect on neutrophil
      survival is observed with dibutyryl cAMP only, whereas supplementation of cell
      cultures with GM-CSF and forskolin results in a progressive reduction of
      antiapoptotic effects exerted by the single compounds. Moreover, although
      dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they
      are still able to modulate the GM-CSF capacity to prolong neutrophil survival
      following anti-Fas IgM cell challenge, with effects similar to those respectively
      exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF may
      negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils,
      likely via the inhibition of adenylate cyclase activity. This would prevent an
      abnormal neutrophil survival as a result of cAMP signaling stimulation, which
      provides a novel insight into the role of GM-CSF as a physiological regulator of
      myeloid cell turnover.

PMID- 9927233
TI  - Epithelium-dependent regulation of airways smooth muscle function. A histamine
      nitric oxide pathway.
AB  - The airway epithelium is responsible for the production of a number of
      arachidonic acid and non-prostanoid inhibitory factors. Epithelium synthesises
      nitric oxide (NO) which may be important in regulating the function of airways
      smooth muscles. We studied in vitro the effect of histamine (100 nM-100 microM)
      which increases the NO release on rabbit airway smooth muscles induced by 80 mM
      KC1 in the presence or not of 10(-5) Methylene blue (MB) (inactivator of
      guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All
      experiments were done in tracheal muscle strips from 28 rabbits with epithelium
      and after epithelium removal. The additional use of histamine (1 microM) on KC1
      contraction induced a relaxation of 10% of the initial contraction. The
      additional use of L-NMMA decreased the relaxation to 5% of initial contraction.
      MB rather than L-NMMA increased the contraction significantly (p<0.01).
      Epithelium removal increased the contraction induced by KC1 (80 mM) and histamine
      (1 microM) by about 30% (p<0.001). NO release especially from epithelium
      regulates the airways smooth muscle functions. Damage to the epithelium may
      contribute to an increase in airways sensitivity, observed in asthma.

PMID- 9927232
TI  - Transient degradation of NF-kappaB proteins in macrophages after interaction with
      mast cell granules.
AB  - The exposure of the macrophage cell line, J774 to mast cell granules (MCG) led to
      the formation of altered nuclear transcription factor proteins (NF-kappaBx),
      which had faster electrophoretic mobility than the p50 homodimer of NF-KB, but
      retained comparable DNA binding capacity. Antibodies to N-terminal peptides of
      p50, p52, p65 or c-Rel supershifted only a fraction of NF-kappaBx. Western blot
      analyses revealed that nuclear p65 and c-Rel were progressively degraded after
      exposure to MCG, whereas nuclear p50 appeared to be unaffected. In contrast,
      cytoplasmic p50, p65, c-Rel as well as IkBalpha remained intact after MCG
      treatment, although p52 was clearly degraded. In comparison to J774 cells,
      incubation of mouse peritoneal macrophages with MCG resulted in more extensive
      alterations to NF-KB proteins. The alterations in NF-KB proteins did not affect
      the expression of inducible nitric oxide synthase (iNOS) or TNF-alpha mRNA inJ774
      cells. These data indicate that exposure of J774 cells to MCG leads to generation
      of altered nuclear p52, p65 and c-Rel, which retain intact N-terminal peptides,
      specific oligonucleotide binding and transactivating activity. On the other hand,
      in peritoneal macrophages, MCG induce more extensive modifications to NF-KB
      proteins with associated inhibition of iNOS or TNF-alpha mRNA expression.

PMID- 9927234
TI  - Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade
      exercise-induced endotoxaemia.
AB  - To address the question of whether translocation of bacterial lipopolysaccharide
      (LPS) into the blood could be involved in the process of exercise-induced
      polymorphonuclear neutrophil (PMN) activation, 12 healthy male subjects who took
      part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road
      race) were studied. While there was no detectable amount of endotoxin in the
      blood samples drawn at rest, exercise was followed by the appearance of
      circulating endotoxin molecules at the end of competition in four subjects, and
      after one and 24 h recovery in three and seven athletes, respectively. The
      concentrations of plasma granulocyte myeloperoxidase ([MPO]), were significantly
      higher immediately after exercise and one hour later-than baseline values
      (P<0.001). This variable returned to pre-race levels the day after exercise,
      despite the presence of detectable amounts of LPS, at that time, in seven
      athletes. The absence of significant correlation (r=0.26; P=0.383) and temporal
      association between [MPO] and plasma endotoxin levels led us to conclude that
      endotoxaemia was not involved in the process of exercise-induced PMN
      degranulation observed in our subjects.

PMID- 9927235
TI  - Acidosis activates complement system in vitro.
AB  - We investigated the in vitro effect of different forms of acidosis (pH 7.0) on
      the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition
      of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to
      heparin blood (N=12) caused significant activation of C3a and C5a compared to
      control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a
      (p=0.003) compared to normocapnic controls. Making blood samples with lactic
      acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory
      compensated metabolic acidosis, C3a and C5a were not increased. These experiments
      show that acidosis itself and not lactate trigger for activation of complement
      components C3 and C5.

PMID- 9927236
TI  - Recent progress in health services research: on the need for evidence-based
      debate.

PMID- 9927237
TI  - Evidence-based medicine: a Kuhnian perspective of a transvestite non-theory.
AB  - Evidence-based medicine (EBM) has been presented by its protagonists as a new
      paradigm for medical practice. In this article that claim is analysed through the
      theory of scientific development proposed by Thomas S. Kuhn in 1962. Traditional
      medical paradigms are discussed, as well as the assumptions of the supposedly
      'new' paradigm of EBM. The value of the results of randomized clinical trials
      (RCTs) for the elaboration of clinical guidelines is analysed within the context
      of the assumptions of EBM and the paradigm concept of Thomas S. Kuhn. It is
      argued that the results of RCTs, whenever contradicted by fundamental medical
      theory, constitute inadmissible evidence for the development of clinical
      guidelines. The supremacy of results of clinical trials over traditional medical
      paradigms, advocated by the protagonists of EBM, is rejected. Fundamental
      contradictions of EBM are also exposed: the fact that there is no evidence to
      support the utility of EBM and its call for a new type of authoritarianism in
      medicine. Finally, it is suggested that 'epidemiology-based medical practice' is
      a better, rhetoric-free designation for what is currently termed 'evidence-based
      medicine'. It is concluded that EBM is not what it claims to be and that its
      assumptions are simply irrational.

PMID- 9927238
TI  - Evidence-based medicine: a new paradigm or the Emperor's new clothes?

PMID- 9927239
TI  - Shortcomings of the randomized controlled trial: a view from the boondocks.
AB  - The randomized controlled trial (RCT), despite its well-known limitations,
      continues to be regarded as a gold standard in determining whether an
      intervention does more harm than good. Some recent evidence suggests that it
      tends to overvalue the modalities it tests. Moreover, the accuracy with which the
      disorder under consideration is diagnosed can be critical to the performance of a
      new intervention designed for it. When technological progress allows us to
      diagnose milder instances, some therapies, possibly useful in dire circumstances,
      will appear ineffective if most of a trial population is at low risk. Human
      individuality makes it impossible to duplicate a RCT. As a result, Popper's
      criterion of falsifiability may not be met and so the carrying out of a large
      scale therapeutic experiment may not be a scientific activity. Finally, it is
      doubtful whether group probabilities derived from RCTs can be safely applied to
      individuals. These and other reservations concerning the applicability of the RCT
      to clinical practice are discussed.

PMID- 9927240
TI  - Clinical guidelines: ways ahead.
AB  - Clinical guidelines are essential in promoting the implementation of evidence
      based practice within the NHS. But there are two broad schools of thought about
      their development and implementation: the first argues that guidelines should be
      entirely evidence-based and tolerates a degree of complexity which may make the
      guideline impractical; the second argues that we need simple guidelines, and
      sacrifices the strength of evidence in favour of ease of application and
      dissemination. Both arguments have merits and flaws, which are discussed, and
      ways to integrate the strengths of both are considered.

PMID- 9927241
TI  - A false dichotomy. Commentary on 'Clinical guidelines: ways ahead'.

PMID- 9927242
TI  - Clinical guidelines tensions: and now where? Commentary on 'Clinical guidelines:
      ways ahead'.

PMID- 9927243
TI  - Clinical guidelines tensions--a legal perspective. Commentary on 'Clinical
      guidelines: ways ahead'.

PMID- 9927244
TI  - Clinical guidelines, EBM and health policy. Evidence based medicine. Commentary
      on 'Clinical guidelines: ways ahead.'.

PMID- 9927245
TI  - Guidelines: time to spin some webs. Commentary on 'Clinical guidelines: ways
      ahead'.

PMID- 9927246
TI  - The guidelines movement: tackling the wrong problem? Commentary on 'Clinical
      guidelines: ways ahead'.

PMID- 9927247
TI  - Including practice data to improve evidence-based guidelines. Example of
      guidelines on the management of thyroid nodules.
AB  - Although clinical guidelines are based on the best evidence available, their
      proliferation has often failed to change actual practice. One of the many
      explanations suggested is that there is a gap between the expectations of the
      targeted professionals and the recommendations in the guidelines. In this study,
      we attempted to take into account the state of current practice and the
      physicians' priorities. Using the example of guidelines on the management of
      thyroid nodules, three different surveys have been conducted: (1) an analysis of
      physicians' expectations and practice through a postal questionnaire to define
      appropriate questions; (2) a survey of the professionals' expert opinions, and
      (3) a prospective study of the use of these guidelines in the management of 253
      patients. The results of these surveys have modified the development of the
      guidelines, and helped us to adapt the content of the guidelines to match
      physicians' practices more closely.

PMID- 9927248
TI  - A model for the development of evidence-based clinical guidelines at local level-
      the Leicestershire Genital Chlamydia Guidelines Project.
AB  - Clinical guidelines can be effective in achieving health gain when they are
      validly developed, disseminated and implemented appropriately. There is, however,
      a potential conflict between the need for validity through use of expert
      resources available at a national level, and implementation, which is undertaken
      at local level and depends on the local relevance of the guideline. This paper
      presents a model by which valid guidelines for the management of a given disease
      (genital chlamydial infection) by general practitioners can be developed at local
      level using the resources available to a district health authority department of
      public health. The model has three elements. First, a district-wide postal
      questionnaire survey was used to document current clinical practice. Secondly, a
      critical review of the evidence relating to the management of genital chlamydial
      infection as it relates to British general practice was performed. Thirdly, the
      information gained from the critical review and survey was used by a
      multidisciplinary group to develop evidence-based guideline recommendations. It
      is argued that the Leicestershire Genital Chlamydia Guidelines compare favourably
      with other recently published national guidelines in terms of their development
      and content. Local guideline development of guidelines for selected topics can be
      practical and appropriate.

PMID- 9927249
TI  - Reviewing and selecting outcome measures for use in routine practice.
AB  - For the successful achievement of evidence-based practice, clinicians, managers
      and purchasers need evidence on whether a particular intervention works and ways
      to judge the appropriateness of the outcome criteria and measures used. Guidance
      is needed on what outcome measure to use, especially within routine clinical care
      settings. Beginning with a reclarification of the difference between a health
      status and an outcome measure, the paper presents an evaluative checklist for use
      by clinical audit and research staff to review outcome measures for use in
      routine care settings. Central features include the user-centredness of the
      measure, its psychometric properties, feasibility of use and utility. The
      applicability of the checklist is illustrated for outcome measurement in diabetes
      and stroke care. A modified form of the checklist is proposed for use by the busy
      clinician as an aid to the critical review of research papers within the context
      of evidence-based practice and to aid health care practitioners' choice of which
      outcome measure(s) to use within routine clinical care.

PMID- 9927250
TI  - The ends of outcomes assessment.
AB  - Outcomes assessment holds great promise to improve the quality and efficiency of
      health care. By subjecting practices to rigorous and systematic analysis, we
      should be in a position to make judgments about what does and does not work in
      clinical practice. However, the outcomes of outcomes assessment themselves should
      be approached with the same critical eye. Among the many sorts of criteria by
      which to evaluate outcomes assessment are several key parameters: foremost among
      them are cognitive outcomes, ethical outcomes, and economic outcomes. Only when
      these outcomes are thoroughly explored and taken into account will the fullest
      potential of outcomes assessment be realized.

PMID- 9927251
TI  - Performance management using health outcomes: in search of instrumentality.
AB  - The past decade has seen the growing use of performance data in the hope of
      bringing about quality improvements in health care. Most recently, an emphasis on
      health outcomes (and especially mortality rates) has led to much activity around
      collecting and publishing such data. Two major problems intervene. What meanings
      can be ascribed to reported health outcomes? And what impacts are they likely to
      have on clinical performance? Much empirical work supports the assertion that
      reported outcomes may be poor indicators of service quality. In addition, the
      impact of these data may be small or even detrimental unless great care is made
      to connect the reporting with explicit quality-improving actions.

PMID- 9927252
TI  - Monitoring of solid phase peptide synthesis by FT-IR spectroscopy.
AB  - Aggregation phenomena of growing peptides on the resin have seldom been
      investigated. We report here how conformations are determined by FT-IR
      spectroscopy. Therefore the sequence 80-99 of HIV 1-protease was synthesized.
      After every coupling a resin sample was taken out of the reaction column and a FT
      IR spectrum recorded. The results were compared with the UV monitoring obtained
      from another synthesis of the same peptide.

PMID- 9927253
TI  - N-Hydroxy-amide analogues of MHC-class I peptide ligands with nanomolar binding
      affinities.
AB  - A novel class of major histocompatibility complex class I (MHC-I) ligands
      containing an N-hydroxyamide bond was designed on the basis of the natural
      epitope SIINFEKL, and synthesized on solid phase. The capacity of these compounds
      to bind to the MHC-I molecule H-2Kb and to induce T cell responses was analysed
      in comparison with the corresponding glycine containing variant of SIINFEKL.
      Binding to the MHC molecule was diminished by the N-hydroxy group at positions 2
      and 3 of the oligomer and improved in the case of positions 4, 5, 6 and 7. No
      change was seen for position 1. The efficacy of T cell stimulation was strongly
      reduced by the modification of all positions except for position 1. A complete
      loss of activity was found for the N-hydroxy variant in positions 4 and 6. N
      Hydroxy amide-containing peptides displayed an enhanced stability to enzymatic
      degradation. This new class of MHC ligand can become instrumental as
      immunomodulatory reagent in various disease situations.

PMID- 9927254
TI  - SPC3, an anti-HIV peptide construct derived from the viral envelope, binds and
      enters HIV target cells.
AB  - SPC3 is a peptide construct (eight branches of the GPGRAF motif) derived from the
      consensus sequence present at the apex of the third variable domain of the human
      immunodeficiency virus (HIV) envelope (Env). It presents a potent anti-HIV
      activity and is currently tested in phase II clinical trials (FDA protocol 257A).
      Its mode of action remains unclear. It was thought that SPC3 exerts its effect
      both during HIV interaction with CD4+ cells but also through interference either
      with a post-binding event or with Env processing. Accordingly, SPC3 was supposed
      to be able to bind and to enter CD4+ cells. In this work, we addressed these
      points. SPC3 was found to interact with CD4+ cell membrane with a K0.5 value in
      the range of 500 nM. The binding of SPC3 to CD4+ cells involves its interaction
      with a cell membrane associated protein which is pronase sensitive and different
      from CD4. This interaction was similar from 2 to 37 degrees C. The maximum
      binding occurred at acidic pH whereas the interaction was inhibited in alkaline
      conditions. We observed also that SPC3 was internalized rapidly into the cells -
      the maximal intracell amount was reached within 30 min - where it remained stable
      for at least 24 h. Altogether, these data suggest that SPC3 can exert its
      antiviral activity via interference with events occurring at the cell surface but
      also into the target cell.

PMID- 9927255
TI  - Synthesis of peptide and pseudopeptide amides inhibiting the proliferation of
      small cell and epithelial types of lung carcinoma cells.
AB  - Small cell lung cancer (SCLC) cell lines produce and secrete various peptide
      hormones, e.g. bombesin (BN)/gastrin releasing peptide (GRP) like peptides that
      are proposed to function as their autocrine growth factors. To inhibit the
      proliferative effect of these hormones we have synthesized short chain BN[7-14]
      analogues replacing the C-terminal peptide bond by a methylene-amino (-CH2NH-)
      unit and introducing D-Phe or D-Ser into position 12. As several substance P (SP)
      analogues were found to inhibit the growth of SCLC cells, some short chain SP
      analogues have been synthesized. (Pseudo)octapeptides were synthesized in
      solution, by fragment condensation using the DCC/HOPfp method. Fragments and SP
      analogues were synthesized stepwise using pentafluorophenyl esters. The
      resistance to hydrolysis of the reduced peptide bond made permitted exact
      quantification of the Leupsi(CH2NH)Leu pseudopeptide in hydrolysates. The binding
      ability of both types of peptides to BN-receptors on Swiss 3T3 mouse fibroblast
      cells and their antiproliferative effect on NCI-H69 human SCLC cell line have
      been tested and compared with a short chain SP-antagonist pHOPA-D-Trp-Phe-D-Trp
      Leu-Leu-NH2 (R) previously described as a potent inhibitor of SCLC proliferation.
      While BN-analogues showed weak activity in inhibition of proliferation of SCLC
      cells, SP-analogues 6: D-MePhe-D-Trp-Phe-D-Trp-Leu(psi)(CH2NH)-Leu-NH2 and 7: D
      MePhe-DTrp-Phe-D-Trp-Leu-MPA, in spite of greatly diminished affinity towards the
      BN-receptor, inhibited SCLC proliferation more effectively than R (6: IC50 = 2
      microM, 7: IC50 = 5 microM and R: IC50 = 10 microM). Moreover, 6 inhibited the
      respiratory activity of SK-MES 1 epithelial type of lung carcinoma cells in
      proliferating but not in the quiescent state, suggesting that the
      antiproliferative effect of these compounds is not due to simple cytotoxicity.
      These short chain analogues of SP might be promising candidates as therapeutic
      agents in the treatment of SCLC.

PMID- 9927256
TI  - Enkephalin analogs containing 4,4-difluoro-2-aminobutyric acid: synthesis and
      fluorine effect on the biological activity.
AB  - Analogs of Met-enkephalin and [D-Pen2, D-Pen5]enkephalin (DPDPE) containing the
      partially fluorinated amino acid 4,4-difluoro-2-aminobutyric acid (DFAB) in the 2
      or 3-position of the peptide sequence were synthesized and their opioid
      activities and receptor selectivities were determined in vitro. The linear
      fluorinated [D-DFAB2, Met5-NH2]enkephalin showed mu and delta agonist potencies
      comparable to those of natural [Leu5]enkephalin. The partially fluorinated DPDPE
      analogs behaved differently as compared with their non-fluorinated correlates.
      While L-amino acid substitution in position 3 of DPDPE usually resulted in higher
      delta agonist potency than D-amino acid substitution. [D-DFAB3]DPDPE turned out
      to be a more potent delta agonist than [L-DFAB3]DPDPE. Furthermore, [D
      DFAB3]DPDPE showed over 100-fold higher delta agonist potency than [D-Abu3]DPDPE
      (Abu = 2-aminobutyric acid), indicating that the fluorine substituents interact
      favorably with a delta opioid receptor subsite.

PMID- 9927257
TI  - The crystal state conformation of Aib-rich segments of peptaibol antibiotics.
AB  - Ac-(Aib-Ala)3-OH (a protected segment of the peptaibols gliodeliquescin and
      paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu]7-gliodeliquescin), Z
      Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin),
      and Ac-Aib-Pro-(Aib-Ala)2-OMe and Z-Aib-Pro-(Aib-Ala)2-OMe, which represent
      differently N(alpha)-protected 1-6 segments of alamethicin and hypelcin, have
      been synthesized by solution methods. The crystal-state conformations of these
      five Aib-containing peptides have been determined by X-ray diffraction analysis.
      We have confirmed that the 3(10)-helical structure is preferentially adopted by
      Aib-rich short peptides. An experimentally unambiguous proof for the 3(10)-
      >alpha-helix conversion has been provided by the two differently N-blocked -Aib
      Pro-(Aib-Ala)2-OMe hexapeptides. The beta-bend ribbon conformation, commonly
      observed in the (Aib-Pro)n sequential oligopeptides, is not found in the -Aib-Pro
      Aib-Ala-Aib-Ala-sequence. As expected on the basis of the L-configuration of the
      C(alpha)-monoalkylated residues, a right-handed helix screw sense was found in
      all peptides investigated.

PMID- 9927258
TI  - Differing epidemiology of Clostridium difficile-associated diarrhea between an
      oncology ward and a general medicine ward.

PMID- 9927259
TI  - Primary bacteremia and needleless safety devices.

PMID- 9927260
TI  - Infection control and hospital epidemiology outside the United States.

PMID- 9927261
TI  - A nosocomial outbreak of malaria associated with contaminated catheters and
      contrast medium of a computed tomographic scanner.
AB  - OBJECTIVE: To identify the risk factors associated with an unexpected outbreak of
      malaria that occurred among seven patients in a general teaching hospital in
      Taipei in October 1995. DESIGN: A three-stage case-control study was conducted to
      identify risk factors. PATIENTS: We identified all 7 patients who were diagnosed
      as malaria cases and 69 controls from those undergoing computed tomography (CT)
      examination. METHODS: Malaria was diagnosed by demonstrating the presence of
      Plasmodium falciparum on either thick or thin blood smears. Clinical
      characteristics and exposure information were collected from medical records and
      patient interviews. RESULTS: The index case was infected by malaria when he
      visited Nigeria in early September and was diagnosed when he was hospitalized in
      hospital A in October. Among 10 patients examined with the Imatron scanner after
      the index case, all 6 who were injected with contrast medium were infected, but
      none of 4 examined without contrast medium were infected (P=.005). CONCLUSIONS:
      This nosocomial outbreak of malaria was most likely due to transmission via a
      contaminated catheter and contrast medium used for CT scanning. Use of disposable
      catheters may avoid such nosocomial outbreaks in the future.

PMID- 9927262
TI  - Risk factors for colonization or infection due to methicillin-resistant
      Staphylococcus aureus in HIV-positive patients: a retrospective case-control
      study.
AB  - OBJECTIVE: To determine the risk factors for colonization or infection with
      methicillin-resistant Staphylococcus aureus in human immunodeficiency virus (HIV)
      infected patients. DESIGN: Retrospective matched-pair case-control study.
      SETTING: Continuity clinic and inpatient HIV service of a university medical
      center. POPULATION: Patients with HIV infection from the general population of
      eastern and coastal Texas and from the Texas Department of Criminal Justice. DATA
      COLLECTION: Patient charts and the AIDS Care and Clinical Research Program
      Database were reviewed for the following: age, race, number of admissions, total
      hospital days, presence of a central venous catheter, serum albumin, total white
      blood cell count and absolute neutrophil count, invasive or surgical procedures,
      any cultures positive for S. aureus, and a history of opportunistic illnesses,
      diabetes, or dermatologic diagnoses. Data also were collected on the
      administration of antibiotics, antiretroviral therapy, steroids, cancer
      chemotherapy, and subcutaneous medications. RESULTS: In the univariate analysis,
      the presence of a central venous catheter, an underlying dermatologic disease,
      lower serum albumin, prior steroid therapy, and prior antibiotic therapy,
      particularly antistaphylococcal therapy or multiple courses of antibiotics, were
      associated with increased risk for colonization or infection with methicillin
      resistant S. aureus. Multivariate analysis yielded a model that included presence
      of a central venous catheter, underlying dermatologic disease, broad-spectrum
      antibiotic exposure, and number of hospital days as independent risk factors for
      colonization or infection with methicillin-resistant S. aureus. CONCLUSIONS: In
      our HIV-infected patient population, prior hospitalization, exposure to broad
      spectrum antibiotics, presence of a central venous catheter, and dermatologic
      disease were risk factors for acquisition of methicillin-resistant S. aureus.

PMID- 9927263
TI  - Methicillin-resistant Staphylococcus aureus and antimicrobial use in Belgian
      hospitals.
AB  - OBJECTIVE: To investigate relationships between the incidence of methicillin
      resistant Staphylococcus aureus (MRSA) and the use of different classes of
      antimicrobials in Belgian hospitals. DESIGN: Using Pearson correlation
      coefficients, the number of new nosocomial MRSA-colonized or -infected patients
      in the second half of 1994 and the first half of 1995 reported by the national
      MRSA surveillance program was compared with use of various antimicrobial classes
      as reported by the National Institute for Sickness and Disability Insurance.
      Relationships between different classes of antimicrobials were evaluated in a
      correlation matrix. MRSA incidence, antimicrobial use, and potential confounding
      factors were included in a multiple linear regression analysis. SETTING: 50
      hospitals in Belgium. RESULTS: The use of a number of different classes of
      antimicrobials was interrelated. In the multivariate analysis, the incidence of
      nosocomial MRSA increased with increasing use of ceftazidime and cefsulodin
      (P=.0003), amoxicillin with clavulanic acid (P=.02), and quinolones (P=.005). No
      association was found between MRSA incidence and total antimicrobial use.
      CONCLUSIONS: The relationships between antimicrobial use and MRSA are complex.
      Interventions aimed at promoting more rational prescribing patterns should be
      supported by adequate experimental and epidemiological evidence. Advice for
      preventing and controlling MRSA has focused mainly on hygienic measures and
      precautions to avoid cross-transmission; the role of relieving antimicrobial
      pressure needs to be clarified.

PMID- 9927264
TI  - Prevalence and risk factors for nosocomial infections in four university
      hospitals in Switzerland.
AB  - OBJECTIVE: To determine the prevalence and risk factors for nosocomial infections
      (NIs) in four Swiss university hospitals. DESIGN AND SETTING: A 1-week period
      prevalence survey conducted in May 1996 in medical, surgical, and intensive-care
      wards of four Swiss university hospitals (900-1,500 beds). Centers for Disease
      Control and Prevention definitions were used, except that asymptomatic
      bacteriuria was not categorized as NI. Study variables included patient
      demographics, primary diagnosis, comorbidities, exposure to medical and surgical
      risk factors, and use of antimicrobials. Risk factors for NIs were determined
      using logistic regression with adjustment for length of hospital stay, study
      center, device use, and patients' comorbidities. RESULTS: 176 NI were recorded in
      156 of 1,349 screened patients (11.6%; interhospital range, 9.8%-13.5%). The most
      frequent NI was surgical-site infection (53; 30%), followed by urinary tract
      infection (39; 22%), lower respiratory tract infection (27; 15%), and bloodstream
      infection (23; 13%). Prevalence of NI was higher in critical-care units (25%)
      than in medical (9%) and surgical wards (12%). Overall, 65% of NIs were culture
      proven; the leading pathogens were Enterobacteriaceae (44; 28%), Staphylococcus
      aureus (20; 13%), Pseudomonas aeruginosa (17; 11%), and Candida species (16;
      10%). Independent risk factors for NI were central venous catheter (CVC) use
      (odds ratio [OR], 3.35; 95% confidence interval [CI95], 2.91-3.80), admission to
      intensive care (OR, 1.75; CI95, 1.30-2.21), emergency admission (OR, 1.57; CI95,
      1.15-2.00), impaired functional status (Karnofsky index 1-4: OR, 2.56; CI95,
      1.953.17), and McCabe classification of ultimately fatal (OR, 2.50; CI95, 2.04
      2.96) or rapidly fatal (OR, 2.25; CI95, 1.52-2.98) underlying condition.
      CONCLUSIONS: According to the results of this survey, NIs are frequent in Swiss
      university hospitals. This investigation confirms the importance of CVCs as a
      major risk factor for NI. Patient comorbidities must be taken into account to
      adjust for case mix in any study comparing interhospital or intrahospital
      infection rates.

PMID- 9927265
TI  - Recurrent Clostridium difficile disease: epidemiology and clinical
      characteristics.
AB  - OBJECTIVE: To describe the epidemiology, diagnosis, risk factors, patient impact,
      and treatment strategies for recurrent Clostridium difficile-associated disease
      (CDAD). DESIGN: Data were collected as part of a blinded, placebo-controlled
      clinical trial testing a new combination treatment for recurrent CDAD.
      Retrospective data regarding prior CDAD episodes were collected from interviews
      and medical-chart review. Prospective data on the current CDAD episode, risk
      factors, and recurrence rates were collected during a 2-month follow-up.
      SETTINGS: National referral study. PARTICIPANTS: Patients with recurrent CDAD.
      INTERVENTIONS: Treatment with a 10-day course of low-dose (500 mg/d) or high-dose
      (2 g/d) vancomycin or metronidazole (1 g/d). RESULTS: Recurrent CDAD was found to
      have a lengthy course involving multiple episodes of diarrhea, abdominal
      cramping, nausea, and fever. CDAD may recur over several years despite frequent
      treatment with antibiotics. Recurrence rates were similar regardless of the
      choice or dose of antibiotic. Recurrent CDAD is not a trivial disease: patients
      may have multiple episodes (as many as 14), may require hospitalization, and the
      mean lifetime cost of direct medical care was $10,970 per patient. Fortunately,
      the disease does not become progressively more severe as the number of episodes
      increase. Two risk factors predictive for recurrent CDAD were found: increasing
      age and a decreased quality-of-life score at enrollment. CONCLUSIONS: Recurrent
      CDAD is a persistent disease that may result in prolonged hospital stays,
      additional medical costs, and rare serious complications.

PMID- 9927266
TI  - Hepatitis B vaccination of personnel employed in Victorian hospitals: are those
      at risk adequately protected?
AB  - OBJECTIVE: To examine the policies and practices in hospitals within the state of
      Victoria, Australia, with respect to vaccination of staff against hepatitis B
      infection. DESIGN: A written self-administered questionnaire to be completed by
      the infection control officer (or designated officer for hepatitis B vaccination)
      within each hospital. SETTING: Public (teaching and nonteaching) and private
      hospitals, including metropolitan and rural institutions in Victoria.
      PARTICIPANTS: A random sample of 30% of Victorian hospitals were asked to
      participate in the survey. Of 78 eligible institutions, 69 (88%) completed and
      returned questionnaires. RESULTS: There was no consistent hepatitis B prevention
      policy in place across Victoria. Of the 69 responding hospitals, 63 (91%) offered
      hepatitis B vaccination to staff, and 58 (84%) of these also paid all costs of
      vaccination. Of the 63 hospitals offering vaccination to staff, 39 offered
      vaccination to all staff, 23 offered vaccination based on job title, and one
      offered vaccination based on anticipated exposure. In many institutions,
      postexposure protocols were recalled more readily than preexposure vaccination
      guidelines. Numerous respondents indicated a need for clear guidelines on policy
      and clarification on practical matters of management, such as acceptable immune
      levels, management of nonresponders to the primary series, and the need for, and
      timing of, booster doses of vaccine. Eleven (18%) of the 63 hospitals offering
      hepatitis B vaccination to staff undertook routine prevaccination screening, a
      practice not generally regarded as cost-effective in Australia. Fifty-five of
      these hospitals (91%) also undertook postvaccination screening. CONCLUSIONS: It
      is evident from this study that a considerable number of potentially susceptible
      healthcare personnel in Victorian hospitals remain unprotected against hepatitis
      B infection. A more reliable and consistent approach to preexposure hepatitis B
      vaccination is recommended.

PMID- 9927267
TI  - An outbreak of Salmonella typhimurium at a teaching hospital.
AB  - An outbreak of Salmonella typhimurium infection in December 1996 affected 52
      patients, relatives, and staff of a large teaching hospital in southeast
      Queensland. Assorted sandwiches were identified as the vehicle of transmission.
      This article describes the outbreak investigation and demonstrates the importance
      of food hygiene and timely public health interventions.

PMID- 9927268
TI  - Inactivation of respiratory syncytial virus by generic hand dishwashing
      detergents and antibacterial hand soaps.
AB  - In an in-vitro test, generic liquid hand dishwashing detergents were as much as
      100-fold more effective than proprietary antibacterial soaps in inactivating
      respiratory syncytial virus (RSV). The use of such detergents for hand washing
      during annual RSV epidemics, or the incorporation of their antiviral components
      into antibacterial soaps might be considered to limit nosocomial spread.

PMID- 9927269
TI  - Bacterial filters in anesthesia: results of 9 years of surveillance.
AB  - In 9 years of surveillance of postoperative lower respiratory infections, the
      infection rate in patients following regional anesthesia was 0.2% and 0.1% in
      patients following general anesthesia. No bacterial filters in the breathing
      circuit were used. Infected patients had risk factors such as type of surgery,
      American Society of Anesthesiologists class > or =2, old age, chronic obstructive
      pulmonary disease, or smoking habits. Infections were not clustered. This
      suggests that, in our setting, patient factors are most important in the
      development of postoperative lower respiratory infections and that the role of
      bacterial filters as a preventive measure is negligible.

PMID- 9927270
TI  - Vancomycin use in a hospital with vancomycin restriction.
AB  - We evaluated vancomycin use in a hospital with endemic vancomycin-resistant
      enterococci and a vancomycin restriction program. Only 68% of vancomycin was
      prescribed appropriately. Inappropriate use was due primarily to empirical
      therapy. In the patients with a microbiological diagnosis following empirical
      therapy, 83% (25/30) had infections due to bacteria sensitive to an appropriate
      antibiotic other than vancomycin. However, only 60% (15/25) of these patients had
      their vancomycin orders changed.

PMID- 9927271
TI  - Risk of transmission and features of hepatitis C after needlestick injuries.
AB  - The rate of transmission and management of needlestick injuries from hepatitis C
      virus (HCV) patients to healthcare workers is still a matter of debate. We used a
      stringent protocol using monthly transaminase levels and polymerase chain
      reaction for HCV RNA to monitor 53 healthcare workers prospectively for up to 6
      months following needle injuries from HCV-positive patients. Evidence of
      transmission of HCV was found in only 2 workers (4%) with mild asymptomatic
      infection, one of which resolved spontaneously. Based on our experience, we now
      use a less-intensive follow-up protocol. Further investigation is required to
      determine the most cost-effective method to monitor individuals who suffer a
      needlestick injury from an HCV-positive patient.

PMID- 9927272
TI  - Rubella immunity in a cohort of pregnant women.
AB  - To assess the rubella immune status of a cohort of high-risk pregnant women
      visiting a Midwestern clinic, we retrospectively studied 50 random pregnancies
      per year from 1990 through 1996. Of 350 patients analyzed, 53 (15.1%) were not
      immune to rubella, and vaccination opportunities were missed.

PMID- 9927273
TI  - Isolation of Ureaplasma urealyticum and Mycoplasma hominis from public toilet
      bowls.
AB  - The presence of Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia
      trachomatis was explored in 50 public restroom toilet bowls. We used culture,
      antigen detection, polymerase chain reaction, and survival assay. Five bowls
      (10%) were contaminated with at least one organism. U. urealyticum was found in
      four bowls, M. hominis in three, and C. trachomatis in one. U. urealyticum
      survived on the toilet rim for up to 2 hours.

PMID- 9927274
TI  - Disinfection of endoscopes: review of new chemical sterilants used for high-level
      disinfection.
AB  - Chemical sterilants are used to high-level disinfect heat-sensitive semicritical
      items such as endoscopes. Most endoscopes have been reprocessed between each
      patient use with glutaraldehyde (>2%) or the Steris System 1. Several new
      chemical sterilants have been developed recently, including 7.5% hydrogen
      peroxide, 0.08% peracetic acid plus 1.0% hydrogen peroxide, and 0.55%
      orthophthalaldehyde. In order to aid the infection control professional in
      choosing the appropriate disinfection methodology, this article reviews the
      characteristics, advantages, and disadvantages of high-level disinfectants
      intended for reprocessing endoscopes.

PMID- 9927275
TI  - Cost reduction with successful implementation of an antibiotic prophylaxis
      program in a private hospital in Ribeirao Preto, Brazil.
AB  - OBJECTIVE: To describe the implementation and results of a perioperative
      antibiotic prophylaxis (PAP) program. DESIGN: A protocol for correct use of PAP
      was implemented in December 1994. For selected months we measured the PAP
      protocol compliance of a random sample of clean and clean-contaminated procedures
      and calculated the cost of incorrect use of PAP. SELLING: A 180-bed general
      hospital in Ribeirao Preto, Brazil. RESULTS: The cost of unnecessary PAP in the
      obstetric and gynecologic, cardiothoracic, and orthopedic services dropped from
      $4,224.54 ($23.47/procedure) in November 1994 to $1,147.24 ($6.17/procedure,
      January 1995), $544.42 ($3.58/procedure, May 1995), $99.06 ($0.50/procedure,
      August 1995), and $30 ($0.12/procedure, March 1996). In November 1994, only 13.6%
      of all surgical procedures were done with correct use of PAP, compared to 59% in
      January 1995, 73% in August 1995, 78% in March 1996, 92% in November 1996, and
      98% in May 1997. CONCLUSIONS: Incorrect PAP use wastes resources, which is a
      particular problem in developing countries. Our program is simple and can be
      implemented without the use of computers and now is being adopted in other
      hospitals in our region. We credit the success of our program to the commitment
      of all participants and to the strong support of the hospital directors.

PMID- 9927276
TI  - Genetic regulation of estrogen responsiveness.

PMID- 9927277
TI  - Interacting quantitative trait loci control phenotypic variation in murine
      estradiol-regulated responses.
AB  - The steroid hormone estradiol (E2) elicits a spectrum of systemic and uterotropic
      responses in vivo. For example, E2 treatment of ovariectomized adult and sexually
      immature rodents leads to uterine leukocytic infiltration, cell proliferation,
      and organ growth. E2-regulated growth is also associated with a variety of normal
      and pathological phenotypes. Historically, the uterine growth response has been
      used as the key model to understand the molecular and biochemical mechanisms
      underlying E2-dependent growth. In this study, genome exclusion mapping
      identified two quantitative trait loci (QTL) in the mouse, Est2 and Est3 on
      chromosomes 5 and 11, respectively, that control the phenotypic variation in
      uterine wet weight. Both QTL are linked to a variety of E2-regulated genes,
      suggesting that they may represent loci within conserved gene complexes that play
      fundamental roles in mediating the effects of E2. Interaction and multiple trait
      analyses using the uterine leukocyte response and wet weight suggest that Est4, a
      QTL on chromosome 10, may encode an interacting factor that influences the
      quantitative variation in both responses. Our results show that E2-dependent
      responses can be genetically controlled and that a genetic basis may underlie the
      variation observed in many E2-dependent phenotypes.

PMID- 9927278
TI  - Skeletal bone morphogenetic proteins suppress the expression of collagenase-3 by
      rat osteoblasts.
AB  - Bone morphogenetic proteins (BMPs) are secreted by skeletal cells, induce the
      differentiation of mesenchymal cells into cells of the osteoblastic lineage, and
      increase their differentiated function. BMPs also decrease collagenase-3
      expression by the osteoblast. We tested the autocrine role of BMPs on collagenase
      3 expression in osteoblast-enriched cells from fetal rat calvariae (Ob cells) by
      examining the effects of noggin, a specific inhibitor of BMP binding and
      function. Although collagenase-3 transcript expression declined in untreated Ob
      cells in culture over a 24-h period, BMP-2, -4, and -6 decreased collagenase-3
      messenger RNA levels in cells treated for 2-24 h. The addition of noggin
      prevented the decrease of collagenase-3 transcripts in control cultures, opposed
      the inhibitory actions of BMP-2, and increased the levels of the protease in the
      culture medium. Noggin did not alter the decay of collagenase-3 messenger RNA in
      transcriptionally arrested cells, and it increased the levels of collagenase-3
      heterogeneous nuclear RNA in Ob cells. In conclusion, noggin enhances the
      synthesis of collagenase-3 in osteoblasts, supporting the notion that BMPs act as
      autocrine suppressors of collagenase-3 in skeletal cells, an effect that may
      contribute to the maintenance of the bone matrix.

PMID- 9927279
TI  - Characteristics of a highly labile human type 5 17beta-hydroxysteroid
      dehydrogenase.
AB  - 17Beta-hydroxysteroid dehydrogenases (17betaHSDs) play an essential role in the
      formation of active intracellular sex steroids. Six types of 17betaHSD have been
      described to date, which only share approximately 20% homology. Human type 5
      17betaHSD complementary DNA is unique among the 17betaHSDs because it belongs to
      the aldo-keto reductase family, whereas the others are members of the short chain
      alcohol dehydrogenases. The characteristics of human type 5 17betaHSD were
      investigated in human embryonic (293) cells stably transfected with human and
      mouse type 5 17betaHSD, as well as human type 3 3alphaHSD. Using intact
      transfected cells, type 5 17betaHSD shows a substrate specificity pattern
      comparable to those of human type 3 17betaHSD and mouse type 5 17betaHSD. These
      enzymes catalyze more efficiently the transformation of androstenedione (4-dione)
      to testosterone, whereas the transformation of dihydrotestosterone to 5alpha
      androstane-3alpha,17beta-diol is much lower. In contrast, type 3 3alphaHSD
      catalyzes more efficiently the transformation of dihydrotestosterone to 5alpha
      androstane-3alpha,17beta-diol, whereas the transformation of 4-dione to
      testosterone represents only 7% of the 3alphaHSD activity. However, upon
      homogenization, human type 5 17betaHSD activity decreases to approximately 10% of
      the activity in intact cells and remains stable at this level together with the
      3alphaHSD activity. Under the same conditions, however, the mouse enzyme is not
      altered by homogenization. Indeed, using purified human 17betaHSD overexpressed
      in Escherichia coli, we could confirm that a much greater amount of protein is
      required to produce activity similar to the enzymatic activity measured in intact
      transfected cells. The present data provide the answer to the question of why
      previous researchers could hardly detect type 5 17betaHSD activity. Indeed, all
      previous publications used cell or tissue homogenates or purified enzymes. Under
      such conditions, only the low level, but stable, 3alphaHSD and 17betaHSD
      activities could be measured, whereas the high level, but highly unstable,
      17betaHSD activity could not be measured. As type 5 17betaHSD shares 84%, 86%,
      and 88% amino acid identity with types 1 and 3 3alphaHSD and 20alphaHSDs,
      respectively, Northern blot analysis used in previous studies could not provide
      unequivocal information. In this report, we used a more specific ribonuclease
      protection assay and could thus show that human type 5 17betaHSD is expressed in
      the liver, adrenal, and prostate; in prostatic cancer cell lines DU-145 and
      LNCaP; as well as in bone carcinoma (MG-63) cells. By analogy with type 3
      17betaHSD, which is responsible for the formation of androgens in the testis, the
      expression of type 5 17betaHSD in the prostate and bone cells suggests that this
      enzyme is involved in the formation of active intracellular androgens in these
      tissues.

PMID- 9927280
TI  - Overexpression of insulin-like growth factor-binding protein-2 in C6 glioma cells
      results in conditional alteration of cellular growth.
AB  - To examine the relationship between the expression of insulin-like growth factor
      (IGF)-binding protein-2 (IGFBP-2) and cell growth in a cell type with a defined
      IGF/IGFBP system, an ovine IGFBP-2 complementary DNA was overexpressed in C6
      glioma cells. C6 cells produce IGFBP-3, IGFBP-4, a negligible amount of IGFBP-2,
      and IGF-I. An ovine IGFBP-2 complementary DNA was transfected into C6 cells, and
      nine colonies that stably expressed variable levels of IGFBP-2 messenger RNA were
      selected. Synthesis of corresponding levels of IGFBP-2 was confirmed by ligand
      blot and immunoblot analyses of conditioned media. Three clones exhibited
      significantly reduced growth rates, and the remainder showed growth rates similar
      to those of the wild-type C6 cells. The clones, which overexpressed high levels
      of IGFBP-2 and IGF-I, had growth rates similar to the wild-type cells, whereas
      the three clones that overexpressed IGFBP-2 without a concomitant increase in IGF
      I had reduced growth rates. In addition, a cell-associated IGFBP was identified
      in the slow growing clones, but not in the wild-type or the fast growing clones.
      This cell-associated IGFBP was deduced to be IGFBP-5 based on its molecular size,
      detection of IGFBP-5 messenger RNA only in slow growing clones, and competition
      of its binding by heparin. Growth of the slow growing clone, C6BP2-1, could not
      be overcome by the addition of exogenous IGF-I, suggesting that the cell
      associated IGFBP-5 was the dominant regulator of IGF action. These observations
      suggested that 1) in C6 glioma cells cellular growth is altered by a disturbance
      in the equilibrium between IGF-I and IGFBPs and/or the functional properties of
      the IGFBPs; and 2) C6 cells may have a limited capacity to modulate IGF/IGFBP
      expression in response to changes in endogenous expression of IGFBPs. Endogenous
      regulation of the balance between IGFs and IGFBPs may be a model of regulation of
      cellular growth in tumor cells.

PMID- 9927281
TI  - Activation of protein kinase C by oxytocin inhibits the biological activity of
      the human myometrial corticotropin-releasing hormone receptor at term.
AB  - The role of placental CRH in human pregnancy is currently unknown. The myometrium
      expresses CRH receptors that during pregnancy become coupled to adenylate
      cyclase. Oxytocin (OT) is one of the main regulators of uterine activity, acting
      via activation of the inositol triphosphate pathway. In view of the possible
      cross-talk between the CRH and OT signal transduction pathways we have sought to
      examine in more detail the second messenger mechanisms involved. CRH receptor
      binding affinity for CRH and activation of adenylate cyclase were reduced in the
      presence of OT in pregnant (at term, but not preterm) human myometrium. OT action
      was mediated via pertussis toxin-sensitive G proteins, which directly inhibit
      adenylate cyclase and, via activation of protein kinase C, phosphorylate the CRH
      receptor, leading to desensitization. Activation of protein kinase C by OT could
      be partially inhibited in human pregnant myometrial cells by OT antagonists (F327
      and CAP476; 1 microM) or phospholipase C inhibitors (U73122; 10 microM). These
      results suggest that in term myometrium, CRH receptor function is modulated by
      OT, leading to reduced biological activity, lower cAMP levels, and a subsequent
      shift in favor of contractility rather than relaxation.

PMID- 9927282
TI  - Changes in mediobasal hypothalamic gonadotropin-releasing hormone messenger
      ribonucleic acid levels induced by mating or ovariectomy in a reflex ovulator,
      the ferret.
AB  - The ferret is a reflex-ovulating species in which receipt of an intromission
      induces a prolonged (+/- 12 h) preovulatory LH surge in the estrous female. This
      LH surge is probably stimulated by a large release of GnRH from the mediobasal
      hypothalamus (MBH). In Exp 1 we asked whether GnRH messenger RNA (mRNA) levels
      increase in response to mating so as to replenish the MBH GnRH stores needed to
      sustain the preovulatory LH surge. Estrous females were killed 0, 0.25, 0.5, 1,
      3, 6, 14, or 24 h after the onset of a 10-min intromission from a male. Coronal
      brain sections ranging from the rostral preoptic area caudally to the posterior
      hypothalamus were processed for in situ hybridization using a 35S-labeled
      oligoprobe complementary to the human GnRH-coding region. We found no evidence of
      increased MBH GnRH mRNA levels during the ferret's mating-induced preovulatory LH
      surge. Instead, the number of GnRH mRNA-expressing cells dropped significantly in
      the arcuate region beginning 6 h after onset of intromission and remained low
      thereafter. Furthermore, cellular GnRH mRNA levels decreased in the arcuate
      region toward the end of the preovulatory LH surge. In Exp 2 we asked whether
      ovarian hormones regulate MBH GnRH mRNA levels in the female ferret. Ovariectomy
      of estrous females significantly reduced the number of GnRH mRNA-expressing cells
      in the arcuate region. This decrease was probably not due to the absence of
      circulating estradiol. Gonadally intact anestrous females had levels of MBH GnRH
      mRNA similar to those in estrous females even though plasma estradiol levels were
      equally low in anestrous females and ovariectomized females. Ovarian hormones
      other than estradiol may stimulate MBH GnRH mRNA levels in anestrous and estrous
      females.

PMID- 9927283
TI  - Developmental regulation of gastric somatostatin secretion in the sheep.
AB  - Gastric somatostatin (SRIF) regulates gastric acidity by inhibiting gastric acid
      and gastrin secretion. SRIF secretion is increased by gastric acidity and also
      directly by regulators of gastric acid secretion such as gastrin. This direct
      effect has not been described in the developing animal, nor have the roles of
      intermediaries such as histamine and gastric acidity been defined. The present
      study aimed to establish the regulatory role of gastrin and histamine during
      development on SRIF secretion and also to determine whether the effects of
      gastrin and histamine are independent of gastric pH. Pentagastrin and histamine
      were infused on separate occasions into fetal sheep, newborn lambs, and 28-day
      old lambs. To determine the roles of endogenous histamine and gastric pH,
      ranitidine (a histamine-2 receptor antagonist) and omeprazole (a H+/K+ ATPase
      inhibitor) were coinfused with the agonists. Plasma SRIF and gastrin
      concentrations were measured by RIA. Pentagastrin stimulated SRIF secretion in
      the fetus after 131 days of gestation (term is 147 days), whereas stimulation by
      histamine was effective only after birth. The SRIF stimulatory effect of
      pentagastrin in 28-day-old lambs was abolished by ranitidine, which also reduced
      this effect in the adult sheep. This inhibitory effect of ranitidine was shown to
      be a result of blockade of stimulatory H2 receptors, because in the adult
      blockade of acid secretion with omeprazole failed to attenuate the response of
      histamine. These results indicate that in the fetus, gastrin receptors, but not
      histamine receptors, are functionally involved in the stimulation of SRIF
      secretion. After birth, both gastrin and histamine stimulate SRIF, but the effect
      of gastrin is mediated at least in part by the release of endogenous histamine.
      These responses occur independently of changes in gastric acidity, supporting the
      concept of a direct negative feedback between SRIF and gastrin.

PMID- 9927284
TI  - Induction of rat aldose reductase gene transcription is mediated through the cis
      element, osmotic response element (ORE): increased synthesis and/or activation by
      phosphorylation of ORE-binding protein is a key step.
AB  - We isolated the rat aldose reductase gene and examined the 5'-flanking sequence
      for the presence of transcription regulatory element responsive to
      hyperosmolarity. Deletion of aldose reductase gene up to -1047 bp abolished the
      transcriptional activation in response to osmotic stimuli in transient
      transfection experiments. A 17-bp sequence [rat osmotic response element (rORE)],
      which is located in bp -1073/-1057 and contains the TGGAAAATCAC sequence, confers
      osmotic response on a heterologous promoter. Electrophoretic mobility shift
      assays using the 17-bp fragment demonstrated that distinct DNA-protein complexes
      (I and II) were formed predominantly with nuclear extracts from the cells exposed
      to hyperosmolarity. When the nuclear extracts were preincubated with calf
      intestinal alkaline phosphatase or protein phosphatase 1, formation of complexes
      I and II was reduced to the control level. However, incubation with protein
      tyrosine phosphatase and addition of antiphosphotyrosine antibody had no effect
      on the complexes. When the nuclear extracts were preincubated with diamide to
      oxidize the thiols, complexes I and II were not affected. Pretreatment of the
      cells with cycloheximide abolished the complexes. All of these data indicate that
      activation by phosphorylation and/or increased synthesis of rORE-binding
      protein(s) are the key steps in induction of transcription of the rat aldose
      reductase gene by hyperosmolarity. Furthermore, we showed that glucose was more
      effective than NaCl in induction of aldose reductase both in transient
      transfection experiments and by Northern blot analysis. The results suggest the
      presence of a glucose-specific mechanism of induction in addition to that by
      NaCl.

PMID- 9927285
TI  - Hormonal induction of mouse selenocysteine transfer ribonucleic acid (tRNA) gene
      transcription-activating factor and its functional importance in the
      selenocysteine tRNA gene transcription in mouse mammary gland.
AB  - Mouse selenocysteine transfer RNA (tRNA) gene transcription-activating factor
      (mStaf) is a transcriptional activator that enhances RNA polymerase III-dependent
      mouse selenocysteine tRNA (tRNA(Sec)) gene transcription. The DNA-binding
      activity of mStaf in mouse mammary gland undergoes developmental changes,
      reaching a maximal level during the period of lactation. In this study, we
      employed an organ culture system to examine the hormonal regulation of mStaf
      binding and its role in the tRNA(Sec) transcription in the mammary gland. The
      results showed that mStaf binding in mammary explants was stimulated by treatment
      with the lactogenic hormones, PRL, insulin, and hydrocortisone and that a
      specific MEK inhibitor, PD98059, inhibited the hormonal stimulation of mStaf
      binding. Other kinase inhibitors, such as a Janus kinase inhibitor and a
      calmodulin kinase inhibitor, had no apparent effect. Northern and Western blot
      analyses revealed that the level of both mStaf messenger RNA and protein was
      enhanced by the lactogenic hormones and was reduced by the concomitant treatment
      with PD98059. The mitogen-activated protein kinase activity in cultured explants
      was rapidly induced and maintained at high levels by the lactogenic hormones. We
      also found that the lactogenic hormones increased the amount of tRNA(Sec) in a
      time-dependent manner, which followed the increase in mStaf binding in cultured
      mammary explants. These results support the view that mStaf plays a key role in
      the hormonal stimulation of tRNA(Sec) transcription in the mammary gland.

PMID- 9927286
TI  - Gene expression of the human glucagon-like peptide-1 receptor is regulated by Sp1
      and Sp3.
AB  - The human glucagon-like peptide-1 (GLP-1) receptor mediates the insulinotropic
      effects of the incretin hormone GLP-1. It is expressed in a cell- and tissue
      specific manner. Recently, we cloned the 5'-region of the GLP-1 receptor gene and
      found that tissue and cell specificity is lost by 5'-deletion to -574. In this
      region proximal to the main transcription start point three putative binding
      sites for Sp1 were localized. Now, in vitro binding of Sp1 was shown by
      deoxyribonuclease footprint analysis with DNA fragments using either recombinant
      Sp1 or nuclear extracts from HIT cells. To elucidate the roles of the three Sp1
      binding sites, we mutated each of the sites individually as well as in different
      combinations. The activity of each construct was analyzed in comparison to the
      wild-type promoter. Mutation of two adjacent Sp1-binding sites showed a clear
      reduction of activity. Contrasting results were obtained after mutation of the
      third, more distal Sp1-binding site. Here, a clear increase (approximately 150%)
      revealed a silencing effect of this cis-regulatory element, possibly resembling a
      Sp3-binding site. Electrophoretic mobility shift analysis revealed binding of Sp1
      and Sp3, which was demonstrated by supershifts using specific antibodies.
      Cotransfection with Sp1 and Sp3 expression vectors in insect cells lacking
      endogenous Sp factors clearly demonstrated the involvement of Sp1 and Sp3.
      Therefore, the basal activity of the GLP-1 receptor gene is mediated by two
      proximal Sp1-binding sites, whereas a more distal site acts as a repressor.

PMID- 9927287
TI  - Unique regulation of CYP17 expression in the trophectoderm of the preattachment
      porcine blastocyst.
AB  - Expression of the gene encoding cytochrome P450 17alpha-hydroxylase, CYP17, is
      necessary for adrenal and gonadal steroidogenesis in most species. However, some
      animals, such as the pig, express CYP17 in the trophectoderm of the preattachment
      blastocyst, an event associated with estrogen synthesis and the establishment of
      pregnancy. How trophoblastic expression of CYP17 is regulated in the porcine
      blastocyst remains unknown and forms the basis of the following studies. The
      porcine CYP17 gene, including the complete coding and several kilobases of 5'
      flanking regions, was cloned and sequenced. Blastocysts were examined by Northern
      analysis to verify the level of CYP17 transcript, and tissue-specific expression
      in the trophectoderm was confirmed by in situ hybridization. Primer extension, S1
      nuclease protection, and 5'-rapid amplification of cDNA ends confirmed a common
      proximal transcription start site in adrenals and gonads (-48 bp) but identified
      a unique distal start site used in porcine trophectoderm (-182 bp). Additionally,
      reporter analysis of the CYP17 regulatory region demonstrated that constructs (
      27 to -718 bp) were unresponsive to forskolin when expressed in porcine
      trophoblast cells, suggesting that trophoblast may not be able to respond to cAMP
      induction of this gene. The identification of this distal, previously
      undescribed, transcriptional start site suggests that unique mechanisms control
      the expression of CYP17 in porcine trophectoderm and possibly other genes
      important in implantation and early placental development.

PMID- 9927288
TI  - Effects of pro- and antioxidative compounds on renal production of
      erythropoietin.
AB  - The most important stimulus for the enhanced synthesis of erythropoietin (Epo) is
      a lowered O2 tension in the tissue. However, the mechanism by which an impaired
      O2 supply is transduced into appropriate Epo production is still not fully
      understood. Recently, studies in human hepatoma cells (line HepG2) indicate that
      reactive O2 species are involved in the signal transduction from the cellular O2
      sensor to the Epo gene. To clarify the role of reactive O2 species in the
      regulation of Epo synthesis in the kidney, the principal Epo-producing organ in
      vivo, we investigated the influence of potent pro- and antioxidants on Epo
      production in isolated perfused rat kidneys. Under normoxic conditions, the iron
      chelator desferrioxamine and the antioxidant vitamin A increased renal Epo
      production, mimicking hypoxic induction. In contrast, supplementation of the
      perfusion medium of hypoxically perfused kidneys with the prooxidant compounds
      H2O2 or pyrogallol caused a significant reduction of Epo synthesis. The
      inhibition of Epo formation by reactive O2 species could be completely
      antagonized by desferrioxamine and the hydroxyl radical-(OH*)-scavenger
      tetramethylthiourea. Vitamin A also antagonized the H2O2-dependent inhibition of
      hypoxically induced Epo synthesis. Interestingly, the addition of the antioxidant
      vitamin A to hypoxically perfused kidneys also induced Epo production
      significantly. Our data strongly support the idea that reactive O2 species,
      especially H2O2, are part of the signaling chain of the cellular O2-sensing
      mechanism regulating the renal synthesis of Epo.

PMID- 9927289
TI  - Parathyroid hormone-related protein markedly potentiates depolarization-induced
      catecholamine release in PC12 cells via L-type voltage-sensitive Ca2+ channels.
AB  - PTH-related protein (PTHrP) is a normal product of many excitable cells of the
      nervous and endocrine systems. Functions of PTHrP in these tissues are, however,
      currently unknown. Prior study has suggested that a relationship exists between
      PTHrP and the L-type voltage-sensitive Ca2+ channel (L-VSCC). For example, in
      cerebellar granule neurons PTHrP gene transcription is regulated by Ca2+ influx
      specifically through this channel. Amino-terminal PTHrP products signal via the
      widely expressed PTH/PTHrP receptor, which is linked to both protein kinase A and
      C. These second messengers are known modulators of L-VSCC conductance. To
      determine whether PTHrP can modulate L-VSCC function, we studied catecholamine
      secretion in a PC 12 clone expressing the PTH/PTHrP receptor but not PTHrP. We
      found that PTHrP(1-36) (100 nM) to be an ineffective secretagogue for resting
      cells, but its presence markedly potentiates secretion to K+ depolarization. The
      PTHrP-augmented catecholamine secretion depends entirely upon L-VSCC Ca2+ influx
      and rapidly inactivates. Similar effects were produced by (Bu)2cAMP but not by
      carbachol. These observations support the hypothesis that PTHrP can regulate L
      VSCC conductance. In the normal adrenal medulla that expresses both PTHrP and its
      receptor, PTHrP may act in an autocrine/paracrine fashion to modify catecholamine
      secretion.

PMID- 9927290
TI  - Estradiol coupling to endothelial nitric oxide stimulates gonadotropin-releasing
      hormone release from rat median eminence via a membrane receptor.
AB  - The median eminence (ME), which is the common termination field for
      adenohypophysiotropic systems, has been shown to produce nitric oxide (NO), a
      signaling molecule involved in neuroendocrine secretion. Using an ex vivo
      technique, 17beta-estradiol exposure to ME fragments, including vascular tissues,
      stimulated NO release within seconds in a concentration-dependent manner, whereas
      17alpha-estradiol or testosterone had no effect. 17Beta-estradiol conjugated to
      BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane
      surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the
      action of both 17beta-estradiol and E2-BSA. Furthermore, estradiol-stimulated NO
      stimulates GnRH release. This was demonstrated by hemoglobin (a NO scavenger),
      N(omega)-nitro-L-arginine methyl ester, and L-N5-(1-iminoethyl)ornithine (nitric
      oxide synthase inhibitors) inhibition of estradiol stimulated NO and GnRH
      release. In this regard, L-N5-(1-iminoethyl)ornithine, specific for endotheliol
      constitutive nitric oxide synthase, was significantly more potent, suggesting
      that the estradiol-stimulated NO release arose from vascular endothelial cells.
      Additionally, the NO-stimulated GnRH release occurs via guanylyl cyclase
      activation in GnRH nerve terminals, as ODQ, a potent and selective inhibitor of
      NO-sensitive guanylyl cyclase, abolished the estradiol-stimulated GnRH release.
      The results suggest that at physiological concentrations, 17beta-estradiol may
      have immediate actions on ME endothelial cells via nongenomic signaling pathways
      leading to NO-stimulated GnRH release.

PMID- 9927291
TI  - Rapid action of 17beta-estradiol on kainate-induced currents in hippocampal
      neurons lacking intracellular estrogen receptors.
AB  - 17Beta-estradiol can potentiate kainate-induced currents in isolated hippocampal
      CA1 neurons. The action of estrogen was rapid in onset, steroid and
      stereospecific, and reversible. The potentiation could be mimicked by 8-bromo
      cAMP, an activator of protein kinase A. As the hippocampus expresses both
      isoforms of the intracellular estrogen receptor (ER alpha and ER beta), the role
      of ERs in the rapid action of 17beta-estradiol remains elusive. Here we report
      that the rapid action of 17beta-estradiol is independent from the classical ER
      activation in the modulation of membrane excitability. Under whole cell voltage
      clamp recording configuration, 17beta-estradiol-induced potentiation was observed
      in both wild-type and the ER alpha gene knockout mice. The perfusion or
      incubation of ICI 182,780, which blocks both ER alpha and ER beta, did not affect
      estrogen potentiation in either group. Further study showed that adenosine 3',5'
      cyclic-monophosphothioate Rp-isomer, a specific inhibitor of protein kinase A,
      completely blocked the potentiation observed with the application of 17beta
      estradiol in ER alpha gene knockout mice. Our results provide evidence that a
      distinct estrogen-binding site exists, which appears to be coupled to alpha-amino
      3-hydroxyl-5-methyl-4-isoxazole proprionic acid/kainate receptors by a cAMP
      dependent phosphorylation process.

PMID- 9927293
TI  - Losartan and angiotensin II inhibit aldosterone production in anephric rats via
      different actions on the intraadrenal renin-angiotensin system.
AB  - Angiotensin II (ANG II) is a major stimulator of aldosterone biosynthesis. When
      investigating the relative contribution of circulating and locally produced ANG
      II, we were therefore surprised to find that ANG II, given chronically s.c. (200
      ng/kg x min), markedly inhibits a nephrectomy (NX)-induced rise of aldosterone
      concentrations (from 10 +/- 2 to 465 +/- 90 ng/100 ml in vehicle infused, and
      from 9 +/- 2 to 177 +/- 35 in ANG II infused rats 55 h after NX and
      hemodialysis). We further observed, by in situ hybridization, that bilateral NX
      increases the number of adrenocortical cells expressing renin and that this rise
      was prevented by ANG II. Moreover, the rise of aldosterone levels was also
      inhibited by the AT1-receptor antagonist, losartan (10 microg/kg x min,
      chronically i.p. from 8 +/- 2 to 199 +/- 26 ng/100 ml), despite the absence of
      circulating renin and a reduction of ANG I to less than 10%. These data
      demonstrate that aldosterone production, after NX, is regulated by an
      intraadrenal renin-angiotensin system and that this system is physiologically
      suppressed by circulating angiotensin. Because the effects of losartan or ANG II
      on aldosterone production involved a latency period of at least 30 h after NX and
      were associated with a modulation or recruitment of renin-producing cells, we
      suggest that the intraadrenal renin-angiotensin system operates via regulation of
      cell differentiation on a long-term scale, rather than or additionally to its
      short-term effects on aldosterone synthase activity.

PMID- 9927292
TI  - Human chorionic gonadotropin induces an inverse regulation of steroidogenic acute
      regulatory protein messenger ribonucleic acid in theca interna and granulosa
      cells of equine preovulatory follicles.
AB  - The time- and gonadotropin-dependent regulation of steroidogenic acute regulatory
      protein (StAR) has not been characterized in vivo in preovulatory follicles of
      large monoovulatory species or sexually mature animals. The objectives of this
      study were to clone equine StAR and describe the regulation of its messenger RNA
      (mRNA) in equine follicles after the administration of an ovulatory dose of hCG.
      The screening of an equine follicle complementary DNA (cDNA) library with a mouse
      StAR cDNA probe revealed two forms of equine StAR that differ only in the length
      of their 3'-untranslated region (3'-UTR); a long form of 2918 bp and a short form
      of 1599 bp. The StAR long form cDNA contains a 5'-UTR of 117 bp, an open reading
      frame (ORF) of 855 bp, and a 3'-UTR of 1946 bp. Primer extension analysis showed
      that the cDNA clone lacked the first 10 bp of the primary transcript, giving a
      total of 127 bp for the complete StAR 5'-UTR. The ORF encodes a 285-amino acid
      protein that is 86-90% identical to StAR of other species characterized to date.
      The regulation of StAR mRNA in vivo was studied in equine preovulatory follicles
      isolated during estrus at 0, 12, 24, 30, 33, 36, and 39 h (n = 4-5 follicles/time
      point) after an ovulatory dose of hCG. Results from Northern blots showed no
      significant changes in StAR mRNA levels after hCG treatment when analyses were
      performed on intact follicle wall (theca interna with attached granulosa cells).
      However, Northern blots performed on isolated follicle cells revealed an
      unexpected regulation of StAR mRNA. In granulosa cells, StAR transcripts were
      undetectable at 0 h but were significantly increased at 30 h post-hCG, and this
      induction was associated with a rise in follicular fluid concentrations of
      progesterone (P < 0.05). In contrast, StAR mRNA levels were high in theca interna
      at 0 h, remained unchanged until 33 h post-hCG, and dropped dramatically
      thereafter (P < 0.05). Thus, this study describes the primary structure of equine
      StAR, documents the regulation of StAR mRNA in vivo in preovulatory follicles of
      a large monoovulatory species, and identifies a novel inverse regulation of StAR
      transcripts in theca interna and granulosa cells of equine follicles before
      ovulation.

PMID- 9927294
TI  - Short-term effects of thyroid hormones on the Na/H antiport in L-6 myoblasts:
      high molecular specificity for 3,3',5-triiodo-L-thyronine.
AB  - The thyroid hormones L-T3 and L-T4 were shown to activate the Na/H antiport in L
      6 cells from rat skeletal muscle by a rapid, nongenomic mechanism. Under pH
      equilibrium conditions, a significant rise in the intracellular pH, measured by
      the fluorescent pH indicator 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein was
      observed after the addition of physiological concentrations (10(-10) M) of either
      L-T3 or L-T4, but with different time courses. L-T3 at all concentrations
      increased the pH after a delay of 2 min, whereas L-T4 showed a concentration
      dependent lag time, going from 11 min at 10(-11) M down to 5 min for a hormone
      concentration of 10(-6) M. The effect of L-T4 was blocked in the presence of the
      5'-deiodinase inhibitor 6-n-propyl-2-thiouracil, suggesting that the difference
      in lag time between L-T3 and L-T4 was due to the 5'-deiodination process that
      transforms L-T4 into the bioactive L-T3. In short term studies (<5 min), a high
      molecular specificity for L-T3 was found, as L-T4, rT3, the D-isomer of T3, and
      the deaminated analogues were ineffective at physiological concentrations. In
      analogy with the results found at equilibrium, intracellular pH recovery from an
      acid load and set-point were increased after 2 min for L-T3 (10(-9) M) and after
      10 min for L-T4 (10(-9) M). The effect of the hormones on the intracellular pH
      was completely blocked by the specific antiport inhibitor 5-(ethyl-N
      isopropyl)amiloride. These findings suggest that thyroid hormones may play an
      active role in the recovery from muscular acidosis through direct stimulation of
      the Na/H antiport.

PMID- 9927295
TI  - Early activation of thyrotropin-releasing-hormone and prolactin plays a critical
      role during a T cell-dependent immune response.
AB  - Functional interaction between the immune and neuroendocrine systems is mediated
      by humoral mediators, neurotransmitters, and cytokines, including TRH and PRL. We
      examined the role of neuroendocrine changes, particularly TRH and PRL, during the
      T cell-dependent immune response. After immunization of rats with sheep red blood
      cells (SRBC, a T cell-dependent antigen), an increase of hypothalamic TRH
      messenger RNA (mRNA) was observed at 4-24 h post immunization, in contrast to the
      decrease observed after treatment with lipopolysaccharide (LPS). During the above
      period, with SRBC, there was an increase in pituitary TRH receptor mRNA and
      plasma PRL levels but no changes in TSH and GH. Also, in contrast to the early
      corticosterone peak induced by LPS, the activation of the hypothalamic-pituitary
      adrenocortical suppressive response appears in a late phase, 5-7 days after SRBC.
      Intracerebroventricular injection of antisense oligonucleotide complementary to
      rat TRH mRNA in conscious freely-moving rats immunized with SRBC resulted in a
      significant inhibition of specific antibody production and a concomitant
      inability to produce the peak in plasma PRL levels. These studies demonstrate,
      for the first time, that the T cell-dependent immune response is critically
      dependent on the early activation of TRH and PRL and that the neuroendocrine
      changes occurring during it are profoundly different from those occurring during
      the T cell-independent and inflammatory responses (LPS model).

PMID- 9927296
TI  - Prenyltransferase inhibitors induce apoptosis in proliferating thyroid cells
      through a p53-independent CrmA-sensitive, and caspase-3-like protease-dependent
      mechanism.
AB  - The inhibitors of protein prenylation have been proposed for chemotherapy of
      tumors. Lovastatin, a 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase
      inhibitor, displays proapoptotic activity in tumor cells blocking the synthesis
      of isoprenoids compounds. To test whether HMG-CoA reductase inhibition can induce
      apoptosis in proliferating thyroid cells, we studied the effects of lovastatin in
      normal and neoplastic thyroid cells and in primary cultures from normal human
      thyroids. In an immortalized human thyroid cell line (TAD-2) and in neoplastic
      cells, lovastatin induced cell rounding within 24 h of treatment. After 48 h the
      cells were detached from the plate and underwent apoptosis, as evidenced by DNA
      fragmentation. Morphological changes and apoptosis did not occur in serum-starved
      quiescent TAD-2 cells or in primary cultures of normal thyrocytes. Mevalonate,
      the product of the HMG-CoA reductase enzymatic activity, and the protein
      synthesis inhibitor cycloheximide completely blocked the effects of lovastatin in
      a dose-dependent fashion. The geranylgeranyl transferase GGTI-298 inhibitor
      mimicked the effects of lovastatin on cell morphology and induced cell death,
      whereas the farnesyl transferase inhibitor FTI-277 was less effective to induce
      both cell rounding and apoptosis. Resistance to lovastatin-induced apoptosis by
      expression of the viral serpine CrmA and by the peptide inhibitor of caspases, Z
      DEVD-fmk, demonstrated the involvement of CrmA-sensitive, caspase-3-like
      proteases. Inhibition of endogenous p53 activity did not affect the sensitivity
      of thyroid cells to lovastatin, demonstrating that this type of apoptosis is p53
      independent. We conclude that lovastatin is a potent inducer of apoptosis in
      proliferating thyroid cells through inhibition of protein prenylation. This type
      of apoptosis requires protein synthesis, is CrmA sensitive and caspase-3-like
      protease dependent, and is independent from p53.

PMID- 9927297
TI  - A role of gamma-amino butyric acid (GABA) and glutamate in control of puberty in
      female rhesus monkeys: effect of an antisense oligodeoxynucleotide for GAD67
      messenger ribonucleic acid and MK801 on luteinizing hormone-releasing hormone
      release.
AB  - Previously we have shown that gamma-aminobutyric acid (GABA) is an inhibitory
      neurotransmitter restricting the pubertal increase in LHRH release in juvenile
      monkeys, and that interfering with GABA synthesis with an antisense
      oligodeoxynucleotide (AS) for glutamic acid decarboxylase (GAD67) mRNA results in
      an increase in LHRH release in prepubertal monkeys. GAD67 is a catalytic enzyme
      that synthesizes GABA from glutamate. To further clarify the role of GABA in
      puberty, we examined whether the inhibition of LHRH release by GABA continues
      after the onset of puberty and whether input from glutamatergic neurons plays any
      role in the onset of puberty when GABA inhibition declines, using a push-pull
      perfusion method. In Study I, the effects of the AS GAD67 mRNA on LHRH release in
      pubertal monkeys (34.3 +/- 1.5 months of age, n = 8) were examined, and the
      results were compared with those in prepubertal monkeys (18.5 +/- 0.4 months, n =
      12). Direct infusion of AS GAD67 (1 microM) into the stalk-median eminence (S-ME)
      for 5 h stimulated LHRH release in both prepubertal and pubertal monkeys.
      However, the increase in LHRH release in pubertal monkeys was significantly (P <
      0.01) smaller than that in prepubertal monkeys. Infusion of a scrambled oligo as
      a control was without effect in either group. In Study II, to examine the
      possibility that an increase in glutamate tone after the reduction of an
      inhibitory GABA tone contributes to the AS GAD67-induced LHRH increase, the
      effects of the NMDA receptor blocker MK801 (5 microM) on LHRH release were tested
      in monkeys treated with AS GAD67. MK801 infusion into the S-ME during the
      treatment of AS GAD67 (1 microM) suppressed the AS GAD67-induced LHRH release in
      both age groups. MK801 alone did not cause any significant effect in either
      group. The data are interpreted to mean that GABA continues to suppress LHRH
      release after the onset of puberty, although the degree of suppression is
      weakened considerably after the onset of puberty, and that the increased LHRH
      release after AS GAD67 treatment may be partly due to an increase in glutamate
      tone mediated by NMDA receptors, as well as due to the decrease in GABA release
      following the decrease in GAD synthesis. Taken together, the present results
      suggest that GAD may play an important role in the onset and progress of puberty
      in nonhuman primates.

PMID- 9927298
TI  - 1,25-Dihydroxyvitamin D3 increases the growth-promoting activity of autocrine
      epidermal growth factor receptor ligands in keratinocytes.
AB  - Topical treatment of normal skin with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or
      its synthetic analogs results in enhanced keratinocyte proliferation. Autocrine
      growth factors belonging to the epidermal growth factor (EGF) family play a major
      role in controlling keratinocyte proliferation. 1,25-(OH)2D3 enhanced the
      autonomous proliferation of HaCaT human keratinocytes in the absence of exogenous
      growth factors. Autonomous and 1,25-(OH)2D3-stimulated proliferations were
      inhibited by a specific inhibitor of EGF receptor (EGFR) tyrosine kinase, an EGFR
      neutralizing antibody, heparin, the heparin antagonist hexadimethrine, and the
      proteoglycan sulfation inhibitor chlorate. These results indicate the involvement
      of proteoglycan-dependent EGFR ligands. The initial events in EGFR (i.e. ErbB1)
      mitogenic signal transduction are dimer formation with another ErbB protein and
      tyrosine cross-phosphorylation. By immunoprecipitation followed by Western
      blotting we showed that ErbB1/ErbB3 heterodimers are the major mitogenic
      signaling entity in 1,25-(OH)2D3-stimulated cells. 1,25-(OH)2D3 did not affect
      the levels of the proteoglycan-dependent EGFR ligands amphiregulin and heparin
      binding EGF nor the synthesis of proteoglycans, as assessed by 35S labeling and
      ion exchange chromatography. 1,25-(OH)2D3 caused a marked increase in the
      cellular contents of ErbB1, ErbB2, and ErbB3 proteins. The increase in ErbB
      proteins that mediates signal transduction by EGFR ligands can account for the
      stimulatory effect of 1,25-(OH)2D3 on autonomous keratinocyte proliferation.

PMID- 9927299
TI  - Mitogen-activated protein kinase cascade is involved in endothelin-1-induced rat
      puerperal uterine contraction.
AB  - The regulation of mitogen-activated protein (MAP) kinase by endothelin-1 (ET-1)
      in cultured rat puerperal uterine myometrial cells was investigated. ET-1 caused
      the rapid stimulation of MAP kinase activity. ET-1-induced MAP kinase activation
      is neither extracellular Ca2+- nor intracellular Ca2+-dependent. ET-1 stimulation
      also led to an increase in phosphorylation of son-of-sevenless (SOS), and
      transfection of dominant negative SOS attenuated the ET-1-induced MAP kinase
      activity. Phorbol-12-myristate 13-acetate (PMA) also induced the MAP kinase
      activity, but pretreatment of the cultured cells with PMA, to down-regulate
      protein kinase C (PKC), did not abolish the activation of MAP kinase by ET-1. In
      addition, down-regulation of PKC had no effect on ET-1-induced SOS
      phosphorylation. Pertussis toxin, which inactivates Gi/Go proteins, blocked the
      ET-1-induced MAP kinase activation but not the PMA-induced MAP kinase activation.
      The results suggested that MAP kinase is acutely activated by ET-1 through a
      pertussis toxin-sensitive G protein and SOS, not through the PMA-sensitive PKC.
      In addition, although reverse-transcriptase PCR assays detected messenger RNA for
      both ET- 1 receptor subtypes in cultured rat puerperal uterine myometrial cells,
      ET-1-induced MAP kinase activity and uterine contraction were blocked by
      treatment with BQ485, an antagonist selective for an ET type A receptor (but not
      by BQ788, an ET type B receptor antagonist). Ritodrine, which is known to relax
      uterine muscle contraction, attenuated ET-1-induced MAP kinase activity. We
      further examined the role of MAP kinase pathway in uterine contraction using an
      inhibitor of MEK activity, PD098059. This inhibitor completely inhibited the ET-1
      induced MAP kinase activation and partially, but significantly, inhibited the ET
      1-induced uterine contraction. These results indicate that ET-1-induced MAP
      kinase signaling cascade may play an important role in the ET-1-induced uterine
      contraction.

PMID- 9927300
TI  - Effect of the genetic background on the reproduction of leptin-deficient obese
      mice.
AB  - Obesity is often associated with an impairment of the hypothalamic-pituitary
      gonadal axis. The leptin-deficient ob/ob mouse model is characterized by a morbid
      obesity with a sterility in males and females that is corrected by continuous
      leptin treatment. Since ob/ob mice are maintained on the C57BL/6J inbred genetic
      background, we sought to determine whether their infertility can be corrected
      without leptin treatment but via the effect of modifier genes brought into the
      obese-sterile phenotype by a different genetic background. Thus, we generated via
      an F2 intercross ob/ob mice on a mixed C57BL/6J-BALB/cJ genetic background and
      assayed them for fertility by mating with wild-type C57BL/6J mice. Whereas
      genetically heterogeneous F2 obese females remained sterile like male and female
      C57BL/6J ob/ob mice, 41% of F2 C57BL/6J-BALB/cJ obese males were capable of
      reproducing despite a morbidly obese state. Therefore, the sterility of the
      original C57BL/6J ob/ob mouse model was genetically corrected independently of
      its obese state via the effects of modifier genes. Unlike testosterone levels,
      triglyceride levels, and testes weight-to-body weight ratios, which were all
      higher in fertile vs. sterile mice, glucose levels were similar in both groups,
      indicating that the underlying hyperglycemia of ob/ob mice was not an impediment
      to the onset of fertility. A genome-wide scan in F2 ob/ob males resulted in the
      localization of four modifier loci on chromosomes 1, 3, 5, and 14 with respective
      quantitative traits consisting of number of pregnancies, testes weights
      normalized to body weights, body weight at 8 weeks of age, and circulating
      testosterone. We conclude that the inheritance of modifier genes at the
      identified loci acts to promote fertility of otherwise sterile leptin-deficient
      obese male mice.

PMID- 9927301
TI  - Neuroendocrine cell type-specific and inducible expression of the secretogranin
      II gene: crucial role of cyclic adenosine monophosphate and serum response
      elements.
AB  - Secretogranin II, an acidic protein in the chromogranin/secretogranin family, is
      widely distributed in neuroendocrine secretory granules. What factors govern such
      widespread, yet selective, expression? The 5' deletions localized neuroendocrine
      cell type-specific expression to the proximal mouse secretogranin II promoter:
      such expression was abolished after deletion past the cAMP response element (CRE;
      [-67 bp]TGACGTCA[-60 bp]), and transfer of the CRE to a neutral promoter
      conferred 3.4- to 5.3-fold neuroendocrine selectivity. Thus, the CRE is, at least
      partly, sufficient to confer tissue-specific expression. Substantial (48-59%)
      loss of cell type-specific expression also occurred upon deletion past the serum
      response element (SRE; [-302 bp]GATGTCC[-296 bp]), and transfer of the SRE to a
      neutral promoter also conferred neuroendocrine selectivity. Expression of both
      the endogenous gene and the transfected secretogranin II promoter was up
      regulated after secretagogues, and the degree of trans-activation of the
      transfected promoter (2.2- to 5.4-fold) paralleled activation of the endogenous
      gene (1.8- to 3.2-fold). The 5' promoter deletions revealed complete loss of
      secretagogue responses after deletion past the CRE. Transfer of the CRE to a
      neutral promoter conferred secretagogue responses (by 2.2- to 18.6-fold).
      Substantial (59-74%) falls in secretagogue responses also occurred after deletion
      past the promoter's SRE. Transfer of the SRE to a neutral promoter conferred
      secretagogue responses (by 2.7- to 8.3-fold). We conclude that the CRE is a
      crucial determinant of cell type-specific constitutive and secretagogue-inducible
      expression of the secretogranin II gene and that the SRE also plays a substantial
      role in both processes.

PMID- 9927302
TI  - Interaction between hypothalamic dopaminergic and opioidergic systems in the
      photoperiodic regulation of pulsatile luteinizing hormone secretion in sheep.
AB  - Previous studies in sheep have shown that whereas the inhibitory effects of
      dopamine (DA) systems on GnRH/gonadotrophin secretion are readily detectable
      during the sexually inactive phase under long days (LD), the suppressive effects
      of endogenous opioid peptide (EOP) systems are most evident during the sexually
      active phase under short days (SD). The hypothesis proposed in this study is that
      inhibitory DA pathways interact with EOP neurons to regulate GnRH/gonadotropin
      secretion in sheep and that photoperiod modulates this interaction to relay its
      effect on the seasonal reproductive cycle. To test this hypothesis, the effects
      of a DA agonist (bromocriptine) or of a DA antagonist (sulpiride) on the
      pulsatile LH response to an opioid antagonist (naloxone) were evaluated in
      sexually active Soay rams exposed to SD, and then reassessed when sexually
      inactive under LD. The experimental design comprised six treatments: 1) control
      (vehicle); 2) bromocriptine; 3) sulpiride; 4) naloxone; 5) pretreatment with
      bromocriptine followed by naloxone; 6) pretreatment with sulpiride followed by
      naloxone. Under SD, when DA pathways are thought to be quiescent and EOP systems
      active, bromocriptine suppressed pulsatile LH secretion (P < 0.01), whereas
      sulpiride had no effect. Under this photoperiod, naloxone induced a conspicuous
      stimulation of episodic LH release (P < 0.01). This effect was prevented by
      pretreatment with bromocriptine (P < 0.01), but was not affected by pretreatment
      with sulpiride. Conversely, under LD, when the activity of DA pathways is thought
      to be increased and that of EOP systems reduced, bromocriptine was without
      effect, whereas sulpiride evoked a mild increase in LH pulse frequency (P <
      0.05). Under this photoperiod, naloxone induced a smaller stimulation than under
      SD. This effect was again blocked by pretreatment with bromocriptine but, in
      contrast to SD, markedly enhanced by pretreatment with sulpiride (P < 0.01).
      Particularly relevant was that the DA agonist blocked the stimulatory effects of
      the EOP antagonist under SD, and that the DA antagonist enhanced the effects of
      the EOP antagonist only under LD. These results are consistent with the
      hypothesis proposing that, in sheep, DA pathways have a predominant inhibitory
      effect on both GnRH and EOP neurons, and that changes in day length modulate the
      interplay between DA and EOP systems as part of the mechanisms involved in the
      photoperiodic control of the seasonal reproductive cycle.

PMID- 9927303
TI  - Free running circadian rhythms of melatonin, luteinizing hormone, and cortisol in
      Syrian hamsters bearing the circadian tau mutation.
AB  - The tau mutation of Syrian hamsters induces a robust reduction in the period of
      circadian activity rhythms, from 24 h (wild-type; tau++) to 22 h (heterozygote;
      tauS+) and 20 h (homozygous mutant, tauSS). Here, we examine the effect of this
      mutation on circadian rhythms of LH, melatonin, and cortisol in ovariectomized
      hamsters. Free running circadian rhythms were observed in all three hormones. In
      each genotype, endocrine rhythms were synchronized with concurrently assessed
      activity rhythms, suggesting a shared period around 20 h in tauSS, 22 h in
      tausS+, and 24 h in tau++. Phasing with respect to the activity rhythm was
      generally similar in tau++ and mutant genotypes. However, melatonin
      concentrations rose significantly earlier in tauSS than in tau++ animals.
      Explanted pineals from both genotypes exhibited a similar time course of response
      to norepinephrine administration, suggesting that the phase advance of melatonin
      production observed in tauSS in vivo is not a direct effect of the tau mutation
      within the pinealocyte. The demonstration of reduced period endocrine rhythms in
      the mutant genotypes extends previous behavioral studies and, together with
      recent work on rhythmicity in the isolated retina, suggests an ubiquitous
      influence of the tau mutation on the processes of circadian rhythm generation in
      this species.

PMID- 9927304
TI  - Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer
      cell lines: a primary role for tyrosine phosphatase SHP-1.
AB  - Somatostatin (SS-14) and its structural analogue SMS 201-995 (SMS) are recognized
      as physiological inhibitors of multiple organs and tissue functions through
      specific membrane receptors (sst1-sst5). The effects of SS-14 and SMS in the
      growth control of the pancreatic cancer cell lines MIA PaCa-2 and PANC-1 were
      investigated to identify and clarify the intracellular events involved. In PANC-1
      cells, SS-14 and SMS caused inhibition of their basal growth, and that stimulated
      by epidermal growth factor, with a maximal effect at 0.1-1 microM. To understand
      the inhibitory mechanisms, we investigated the effects of SS-14 and SMS on
      phosphotyrosine phosphatase (PTPase) activity and, more specifically, that of
      tyrosine phosphatase SHP-1 (PTP1C). SS-14 and SMS caused significant increases in
      total cellular PTPase activity, and particularly SHP-1, with maximal activation
      within 1 min. Inhibition of membrane tyrosine kinase and p42 MAP kinase
      activities was also observed, in response to SS-14 and SMS. In MIA PaCa-2 cells,
      SS-14 and SMS were associated with a positive growth response at 1-10 nM, after 4
      days of culture in serum-free medium. Total cellular PTPase activity was slightly
      increased, but SHP-1 activity could not be detected; its absence in this cell
      line was confirmed by Western blot. Membrane tyrosine kinase activities were
      significantly increased by SS-14 and SMS at concentrations needed for maximal
      growth. p44/p42, which are constitutively active in this cell line, and p38
      activities were not affected by somatostatin. In conclusion, somatostatin can
      exert different effects on human pancreatic cancer cell growth, depending upon
      the presence or absence of SHP-1. This enzyme can play a key role in the control
      of cell proliferation, and its cellular presence may determine the therapeutic
      potential of somatostatin in the control of cancer cell growth.

PMID- 9927305
TI  - Initiation of increased pancreatic islet growth in young normoglycemic mice (Umea
      +/?).
AB  - Pancreatic islets from obese hyperglycemic mice are large and contain a high
      proportion of normally functioning beta-cells. We have previously shown that
      young obese mice have an elevated beta-cell proliferation rate at 3 weeks of age.
      We now wanted to investigate possible factors involved in the initiation of islet
      growth, including blood glucose, C peptide, glucagon-like peptide-1, vasoactive
      intestinal polypeptide, and L-5-hydroxytryptophan. We found that the increased
      beta-cell proliferation on day 20 precedes the rise in blood glucose by 2 days.
      The islet cell proliferation, measured as the 5-bromo-2'-deoxyuridine labeling
      index, in 20-day-old lean mice, was enhanced in a dose-dependent manner when
      glucagon-like peptide-1 or C peptide was injected s.c. for 2 days. L-5
      Hydroxytryptophan inhibited the proliferation. C Peptide also increased the islet
      cell labeling index during islet culture. We conclude that in addition to the
      effect of glucose, islet proliferation can be triggered by other factors involved
      in the physiological regulation of increased insulin release. Stimulation of
      islet proliferation may be related to the actual release of insulin, and C
      peptide may function as a mediator of such responses.

PMID- 9927306
TI  - Regional expression of the type 3 iodothyronine deiodinase messenger ribonucleic
      acid in the rat central nervous system and its regulation by thyroid hormone.
AB  - Type 3 iodothyronine deiodinase (D3) is a selenoenzyme that inactivates thyroid
      hormone. It is necessary for T3 homeostasis in the central nervous system. D3
      activity has been identified in many regions of the brain and parallels thyroid
      status, but the level at which it is regulated and its specific cellular
      locations are not known. We evaluated the effect of thyroid status on the
      expression of the D3 gene within the central nervous system using in situ
      hybridization histochemistry. D3 messenger RNA (mRNA) was identified throughout,
      but with high focal expression in the hippocampal pyramidal neurons, granule
      cells of the dentate nucleus, and layers II-VI of the cerebral cortex. In every
      region, D3 mRNA abundance was correlated with thyroid status. Four different D3
      transcripts were identified by Northern analyses, with evidence for region
      specific processing, and D3 mRNA increased 4- to 50-fold from the euthyroid to
      the hyperthyroid state. D3 mRNA was not detectable in hypothyroid brain. In the
      central nervous system, the D3 gene is highly T3 responsive, and its focal
      localization within the hippocampus and cerebral cortex suggests an important
      role for T3 homeostasis in memory and cognitive functions.

PMID- 9927307
TI  - Luteinizing hormone-releasing hormone quantified in tissues and slice explant
      cultures of postnatal rat hypothalami.
AB  - LH-releasing hormone (LHRH) peptide from postnatal rat preoptic area
      (POA)/hypothalamic tissues in vivo and slice explant cultures maintained in vitro
      was quantitated using an enzyme-linked immunosorbant assay. Moreover, messenger
      RNA (mRNA) copy number was calculated in LHRH neurons maintained in culture using
      in situ hybridization histochemistry with autoradiographic film analysis.
      POA/hypothalami from postnatal day 5-6 pups averaged 1250 pg of LHRH, with
      approximately 28% of peptide residing within rostral tissues where most LHRH
      perikarya reside. Explant cultures maintained 18 days in vitro contained 30.4
      92.0 pg/slice with a whole animal total of 244.8 pg. Considering cell numbers in
      vivo and in vitro, LHRH neurons in whole animal produce 1.0 pg of LHRH/cell,
      whereas those in culture average 2.0 pg/cell. Furthermore, LHRH mRNA copies/cell
      in organotypic culture was estimated conservatively at 1410 copies/cell, a
      relatively high number. This work shows that, compared with whole animal,
      cultures have substantial LHRH stores, indicating maturation of synthetic
      activity and/or formation of new terminals in vitro. High LHRH mRNA copy number
      also suggests a high rate of peptide biosynthesis. Our analysis, demonstrating
      the dynamic potential of LHRH neurons, suggests that subtle changes in LHRH mRNA
      expression in all cells or a subpopulation can dramatically alter the LHRH system
      biosynthetic capacity.

PMID- 9927308
TI  - Novel ligands that function as selective estrogens or antiestrogens for estrogen
      receptor-alpha or estrogen receptor-beta.
AB  - We report on the identification of novel, nonsteroidal ligands that show
      pronounced subtype-selective differences in ligand binding and transcriptional
      potency or efficacy for the two estrogen receptor (ER) subtypes, ER alpha and ER
      beta. An aryl-substituted pyrazole is an ER alpha potency-selective agonist,
      showing higher binding affinity for ER alpha and 120-fold higher potency in
      stimulation of ER alpha vs. ER beta in transactivation assays in cells. A
      tetrahydrochrysene (THC) has a 4-fold preferential binding affinity for ER beta;
      it is an agonist on ER alpha, but a complete antagonist on ER beta. Intriguingly,
      the antagonist activity of THC is associated with the R,R-enantiomer (R,R-THC).
      The S,S-enantiomer (S,S-THC) is an agonist on both ER alpha and ER beta but has a
      20-fold lower affinity for ER beta than R,R-THC. This difference in binding
      affinity accounts for the full ER beta antagonist activity of the THC racemate (a
      1:1 mixture of R,R-THC and S,S-THC). These compounds should be useful in probing
      the conformational changes in these two ERs that are evoked by agonists and
      antagonists, and in evaluating the distinct roles that ER beta and ER alpha may
      play in the diverse target tissues in which estrogens act.

PMID- 9927309
TI  - Expression and activity of 3beta-hydroxysteroid dehydrogenase/delta5-delta4
      isomerase in the rat Purkinje neuron during neonatal life.
AB  - Recently, we demonstrated that cytochrome P450 side-chain cleavage enzyme
      (P450scc) occurs in the rat cerebellar Purkinje cell after differentiation and
      remains during neonatal development and into adulthood. 3Beta-hydroxysteroid
      dehydrogenase/delta5-delta4-isomerase (3betaHSD) is also an essential enzyme for
      progesterone biosynthesis not only in peripheral steroidogenic glands but also in
      the nervous system. In the present study, therefore, the expression of 3betaHSD
      in the rat cerebellum was investigated during neonatal development and in the
      adult. RT-PCR analysis showed that the expression of 3betaHSD messenger RNA
      (mRNA) in the cerebellum was higher at 7-14 days of age than at other times.
      Biochemical studies together with HPLC analysis revealed that cerebellar slices
      at 10 days of age converted pregnenolone to progesterone, suggesting enzymatic
      activity of 3betaHSD. This conversion was significantly reduced by trilostane, a
      specific inhibitor of 3betaHSD. A specific RIA indicated that progesterone
      concentrations in the cerebellum were higher at 3 and 10 days of age than at 60
      days of age. The progesterone level in the cerebellum was significantly higher
      than that in plasma at 10 days of age. In contrast, the concentrations in both
      cerebellum and plasma at 3 and 60 days of age were similar. In the present study,
      the site of 3betaHSD mRNA expression in the cerebellum was further examined in
      neonatal and adult rats using in situ hybridization. The cerebellar expression of
      3betaHSD mRNA was obscure at 3 days of age, whereas intense expression occurred
      in Purkinje cells and external granule cells throughout the cerebellum at 10 days
      of age. 3BetaHSD mRNA was also expressed in Purkinje cells and granule cells at
      60 days of age, but a restricted expression was observed along the cerebellar
      meninges. These results suggest that the steroidogenic enzyme 3betaHSD as well as
      P450scc are expressed at least in the cerebellar Purkinje cell. The expression of
      3betaHSD, however, may increase for a limited period around 10 days of age,
      unlike P450scc.

PMID- 9927310
TI  - Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by
      leptin and stimulated by fasting.
AB  - Agouti-related protein (AGRP) is a homologue of the agouti gene product and, when
      overexpressed, promotes obesity. Like neuropeptide Y (NPY) messenger RNA (mRNA),
      AGRP mRNA is produced in the hypothalamic arcuate nucleus and is elevated in
      leptin-deficient ob/ob and leptin-resistant db/db mice. These data suggest that
      AGRP mRNA might be affected by leptin and nutritional status in parallel with NPY
      mRNA. To test this hypothesis, we examined if AGRP mRNA would be, like NPY mRNA,
      inhibited by leptin injections and stimulated by fasting. AGRP mRNA was elevated
      in ob/ob mice about 5-fold compared with wild-type controls and was significantly
      inhibited by leptin treatment, as assessed by Northern blot analysis. In wild
      type mice, AGRP mRNA was increased at least 13-fold by a 2-day fast, as assessed
      both by Northern blot analysis and in situ hybridization. In ad lib fed db/db
      mice, AGRP mRNA was elevated about 8-fold compared with ad lib fed wild-type
      controls, and was further increased by fasting in db/db mice. These data suggest
      that AGRP mRNA and NPY mRNA respond similarly to leptin and fasting.

PMID- 9927311
TI  - Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide
      (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a
      follicle survival factor.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide
      with considerable homology to vasoactive intestinal peptide and GH-releasing
      hormone, exists in two biologically active forms, PACAP-38 and -27. The presence
      of PACAP in the ovary has been demonstrated, where it stimulates steroidogenesis
      and cAMP accumulation in cultured granulosa cells. In the present study,
      gonadotropin regulation of PACAP gene expression was examined in PMSG/human (h)CG
      treated immature rat ovaries and cultured preovulatory follicles. Northern blot
      analysis of ovaries obtained from PMSG/hCG-treated immature animals revealed the
      transient induction of PACAP transcripts by hCG, reaching a maximum at 6 h. The
      major cell types expressing PACAP messenger RNA were granulosa cells of
      preovulatory follicles and some theca/interstitial cells. In preovulatory
      follicles cultured in serum-free medium, PACAP transcripts were transiently
      induced by LH and FSH, reaching a maximum 6-9 h after stimulation in granulosa
      cells but not in theca cells. Treatment with cycloheximide or alpha-amanitin
      abolished LH-induced PACAP transcripts, indicating that new protein synthesis and
      transcription are necessary. Treatment with MDL-12,330A, an inhibitor of
      adenylate cyclase, inhibited LH-induced PACAP messenger RNA, and forskolin
      mimicked the LH action, implying the role of adenylate cyclase activation. In
      contrast, treatment with chelerythrine, an inhibitor of protein kinase C, and 2-O
      tetradecanol-phorbol-13-acetate had no effect. We further tested the role of
      PACAP in follicle apoptosis using apoptotic DNA fragmentation analysis. Treatment
      with PACAP-38 suppressed follicle apoptosis in a dose-dependent manner. Moreover,
      the LH suppression of follicle apoptosis was partially blocked by cotreatment
      with PACAP-38 antagonist, indicating mediation by endogenous PACAP-38. These
      results suggest that PACAP, transiently induced by the gonadotropin surge, could
      be a local regulator of a number of events and may act as a follicle survival
      factor during the periovulatory period.

PMID- 9927312
TI  - Progesterone can block transmission of the estradiol-induced signal for
      luteinizing hormone surge generation during a specific period of time immediately
      after activation of the gonadotropin-releasing hormone surge-generating system.
AB  - The preovulatory GnRH/LH surge in the ewe is stimulated by a rise in the
      circulating estradiol concentration that occurs in conjunction with preovulatory
      ovarian follicle development. In the presence of high levels of progesterone,
      such as during the luteal phase of the estrous/menstrual cycle, the stimulatory
      effects of elevated estradiol on GnRH/LH secretion are blocked. Recent work in
      the ewe has shown that a relatively short period of estradiol exposure can
      stimulate a GnRH/LH surge that begins after estrogenic support has been removed.
      This result suggests that surge generation is characterized by an estradiol
      dependent period (during which the signal is read) and an estradiol-independent
      period (during which a cascade of neuronal events transmits the stimulatory
      signal to the GnRH neurosecretory system, which releases a surge of GnRH). In
      this series of studies, we addressed the hypothesis that progesterone can block
      transmission of the stimulatory estradiol signal after it has been read. Nine
      ovariectomized ewes were run through repeated artificial estrous cycles by
      sequential addition and removal of exogenous steroids. In study one, ewes
      received three treatments in a randomized cross-over design. Exposure to a
      follicular phase estradiol concentration for 10 h (positive control treatment)
      stimulated an LH surge in all ewes, as determined in hourly jugular blood
      samples. Maintenance of luteal phase progesterone concentrations throughout the
      artificial follicular phase (2 x CIDR-G devices, negative control) blocked the
      stimulatory effects of a 10-h estradiol signal, and no ewes that received this
      treatment expressed an LH surge. In the experimental group, exposure to luteal
      phase levels of progesterone, during the period after the surge generating system
      had been activated by estradiol, blocked the LH surge in six of nine ewes. This
      result demonstrates that progesterone can block the surge, even when applied
      after the surge-generating system has been activated and, therefore, that it
      inhibits either the transmission of the estradiol signal and/or the release of
      the GnRH/LH surge. In study 2, we assessed whether sensitivity to the inhibitory
      effects of progesterone was confined to a specific stage of the transmission of
      the estradiol signal. Eight ewes were exposed to four treatments, over successive
      artificial estrous cycles. Positive and negative controls were similar to those
      described in Study 1, except the duration of the stimulatory estradiol signal was
      reduced to 8 h. The two experimental groups consisted of an EARLY P
      (progesterone) treatment, in which progesterone was given from hours 8-13 after
      estradiol insertion (immediately after estradiol removal), and a LATE P
      treatment, in which progesterone was given from hours 13-18 (immediately before
      LH surge secretion). As expected, LH surges were stimulated and blocked, in
      response to the positive and negative controls, respectively. Whereas the EARLY P
      treatment blocked the LH surge in seven of eight ewes, the LATE P treatment was
      only successful in inhibiting a surge in one of eight animals. This result
      demonstrates that progesterone can block the estradiol-induced surge-generating
      signal soon after the onset of signal transmission (immediately after estradiol
      removal) but not during the later stages of signal transmission (at the time of
      GnRH/LH surge onset).

PMID- 9927313
TI  - Isoform-specific regulation of the CCAAT/enhancer-binding protein family of
      transcription factors by 3',5'-cyclic adenosine monophosphate in Sertoli cells.
AB  - The C/EBP (CCAAT/enhancer-binding protein) family of transcription factors is
      important for differentiation, lipid biosynthesis, and metabolism. Here, we
      demonstrate for the first time the presence of C/EBP alpha, beta, delta, and zeta
      messenger RNA (mRNA) and protein in Sertoli cell primary cultures. Treatment with
      FSH or 8-CPTcAMP strongly induced C/EBP beta mRNA above basal levels with rapid
      and transient kinetics in Sertoli cell primary cultures as well as in whole
      testes from hypophysectomized rats. Whereas C/EBP beta mRNA was induced
      approximately 50-fold, C/EBP delta mRNA was induced 5- to 8-fold by cAMP in
      Sertoli cells. Messenger RNA for C/EBP beta and delta were induced by inhibition
      of protein synthesis with cycloheximide and cycloheximide acted synergistically
      with cAMP. Immunoblots with C/EBP antibodies demonstrated a strong induction of
      C/EBP beta, delta, and zeta by cAMP. Electrophoretic mobility shift analysis of
      nuclear proteins from cAMP-treated Sertoli cells using a C/EBP consensus
      oligonucleotide and antibodies revealed specific binding of C/EBP/DNA complexes,
      the majority of which were supershifted by C/EBP beta antibody. Transfections of
      Sertoli cells with a C/EBP reporter construct showed approximately 3-fold
      induction of reporter gene activity by cAMP. In contrast, the reporter gene
      vector with a mutated form of the C/EBP binding site, was almost unresponsive to
      cAMP in transfections of Sertoli cells. Furthermore, C/EBP beta expression
      increased the activities of two promoters known to be cAMP-responsive in Sertoli
      cells. Thus, the early induction of C/EBP isoforms by cAMP may play a role in FSH
      dependent regulation of late response genes in Sertoli cells.

PMID- 9927314
TI  - Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in
      the developing rat.
AB  - Thyroid hormone (TH) is essential for normal development in vertebrate species.
      Although the mechanisms by which TH regulates developmental processes are not
      fully understood, intracellular T3 levels are likely to be a critical aspect of
      the process. Furthermore, as different tissues and organs have specific temporal
      patterns of development, their T3 requirements may vary widely. Differential
      regulation of intracellular T3 levels in peripheral tissues as a result of
      differences in the activities of the three iodothyronine deiodinases (D1, D2, and
      D3) could offer an important means of achieving coordination of T3-dependent
      developmental processes among tissues. To obtain evidence for this concept we
      have documented the levels of expression of all three types of deiodinase in 11
      tissues of the fetus, the neonate, and the adult rat. In most fetal tissues, D3
      was the predominant deiodinase, but it declined after birth as the activities of
      D1 and D2 increased. Exceptions to this pattern were skin and brown adipose
      tissue (BAT), in which D2 activity was highest in the fetus, and testis and
      thyroid in which D2 activity was higher in the neonate than in the adult. D1 was
      the only 5'D enzyme expressed in liver, kidney and intestine at all stages
      studied, and D3 was not expressed in these tissues after birth. Thyroid,
      pituitary, and BAT expressed either D2 or D2 plus D1, but did not express D3 at
      any stage studied. Cerebrum, cerebellum, ovary, testis, skin, and placenta
      expressed all three deiodinases. Two other points were evident. First, the
      maximum 5'D activity attained, and thus presumably the amount of T3 generated, in
      liver, kidney, intestine, thyroid, pituitary, and BAT was very much higher than
      that in cerebrum, cerebellum, ovary, testis, skin, and placenta. Second, in the
      tissues where 5'D activity was relatively low, coexpression of D3 with D1 and D2
      was the general rule, suggesting the need for very tight control of intracellular
      T3 levels. The findings are consistent with the view that the deiodinases play a
      major role in achieving the intracellular T3 levels that are optimal for the
      development of each tissue. Additional studies are in progress to demonstrate the
      functional consequences of these deiodinase expression patterns.

PMID- 9927315
TI  - The Fas system, a regulator of testicular germ cell apoptosis, is differentially
      up-regulated in Sertoli cell versus germ cell injury of the testis.
AB  - Sertoli cells, the supportive cells in the seminiferous epithelium, orchestrate
      spermatogenesis by providing structural and nutritional support to germ cells. In
      the rat, physiological apoptosis occurs continuously to limit the size of the
      germ cell population to numbers that can be adequately supported. This form of
      germ cell death is exaggerated after testicular insults such as toxicant
      treatment, radiation, and heat exposure. The Fas system has been proposed as a
      key regulator of the activation of germ cell apoptosis. According to this model,
      Fas ligand (FasL) and Fas, expressed by Sertoli cells and germ cells,
      respectively, respond to environmental conditions and initiate germ cell death.
      To assess the role of the Fas system in various testicular injury models, a
      semiquantitative RT-PCR technique was used to evaluate the expression kinetics of
      both FasL and Fas after induction of massive germ cell death. Radiation exposure,
      which targets actively dividing germ cells, produced an up-regulation of Fas gene
      expression, but not FasL gene expression. However, administration of mono-(2
      ethylhexyl)phthalate and 2,5-hexanedione, two widely studied Sertoli cell
      toxicants, resulted in up-regulated expression of both FasL and Fas. These data
      support the following hypotheses: 1) up-regulation of Fas is a common and
      critical step for initiating germ cell death in vivo; and 2) if Sertoli cells are
      injured, Sertoli cells up-regulate FasL to eliminate Fas-positive germ cells,
      which cannot be supported adequately.

PMID- 9927316
TI  - Developmental expression of the peripheral-type benzodiazepine receptor and the
      advent of steroidogenesis in rat adrenal glands.
AB  - Although the precise mechanism whereby cholesterol is transported across the
      outer mitochondrial membrane is uncertain, a multimeric receptor complex termed
      the peripheral-type benzodiazepine receptor (PBR) appears essential for this
      process. We therefore predicted that adrenal cells at different developmental
      stages would express PBR coincidentally with the advent of steroidogenesis.
      Adrenals of neonatal rats demonstrate greatly reduced sensitivity to ACTH that
      gradually increases after the first 2 weeks of life. Thus, neonates have lower
      circulating corticosterone levels following exposure to stress. We examined
      mitochondrial PBR ligand binding activity, immunoreactive (ir) PBR content, and
      adrenal sensitivity to ACTH in vivo and in vitro. Ontogeny of both mitochondrial
      PBR ligand binding capacity and irPBR directly paralleled that of ACTH-inducible
      steroidogenesis in isolated rat adrenal cells and in rats injected with ACTH. In
      addition, neonatal PBR had approximately 2-fold higher affinity for PK11195, a
      synthetic ligand that binds with high affinity to PBR. No correlation was
      observed during neonatal life between ir-steroidogenic acute regulatory (StAR)
      protein content and steroidogenesis. These results are consistent with the
      hypothesis that PBR is an absolute prerequisite for adrenocortical
      steroidogenesis, and suggest that the stress hyporesponsive period of neonatal
      rats may result from decreased PBR expression. In addition, the higher affinity
      of neonatal PBR and the relatively high basal expression of StAR protein in
      neonatal adrenals may partly explain the high constitutive steroidogenesis
      characteristic of neonatal rat adrenal cells.

PMID- 9927317
TI  - Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic
      acini.
AB  - Adrenomedullin is a novel hypotensive peptide originally isolated from human
      pheochromocytoma and recently localized to PP cells of the pancreatic islets of
      Langerhans. Based on the pancreatic islet-acinar axis model, we investigated the
      effect of adrenomedullin on regulated exocytosis of exocrine pancreas. Using rat
      [125I]-adrenomedullin, specific binding sites were localized to rat pancreatic
      acini. We next examined the effect of adrenomedullin on 100 pM cholecystokinin
      (CCK)-stimulated amylase release from pancreatic acini. Adrenomedullin inhibited
      amylase secretion in a dose-dependent manner by approximately 50% at maximum, and
      the IC50 was 1.1 pM. However, adrenomedullin did not affect rat [125I]CCK binding
      to isolated acini or reduce the intracellular free Ca2+ concentration increased
      by CCK. Adrenomedullin also inhibited amylase secretion induced by 1 microM
      calcium ionophore A23187, suggesting that adrenomedullin inhibits stimulated
      amylase secretion by functioning at a step(s) distal to the ligand-receptor
      binding system and intracellular calcium mobilizing mechanism. In streptolysin-O
      permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve
      to the right, indicating that adrenomedullin inhibits calcium-induced amylase
      secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery.
      In addition, pretreatment of pancreatic acini with pertussis toxin abolished the
      inhibitory effect of adrenomedullin on CCK-stimulated amylase secretion. These
      results indicate that adrenomedullin inhibits stimulated amylase secretion by
      reducing the calcium sensitivity of the exocytotic machinery of the pancreatic
      acini. A pertussis toxin-sensitive GTP-binding protein(s) is also involved in
      this mechanism.

PMID- 9927318
TI  - Insulin-like growth factor I suppresses parathyroid hormone (PTH)/PTH-related
      protein receptor expression via a mitogen-activated protein kinase pathway in UMR
      106 osteoblast-like cells.
AB  - Insulin-like growth factor I (IGF-I) is important in skeletal growth and has been
      implicated in the maintenance of bone integrity. PTH stimulates bone resorption
      through the G protein-linked PTH/PTH-related protein (PTHrP) receptor in
      osteoblasts. Using a heterogeneous nuclear RNA assay and Northern blot analysis,
      we showed that IGF-I inhibited expression of the gene for PTH/PTHrP receptor in a
      dose- and time-dependent fashion, but did not alter the stability of the receptor
      messenger RNA (mRNA) in UMR-106 osteoblast-like cells. IGF-I treatment for 48 h
      also caused a decrease in the receptor number to 45% of that in controls without
      affecting receptor affinity and in functional receptor expression to 50-60% of
      that in controls as measured by PTH-stimulated cAMP production. In MC3T3-E1
      murine nontransformed osteoblasts, IGF suppressed receptor mRNA expression dose
      dependently. In UMR-106 cells, IGF-I induced the mitogen-activated protein (MAP)
      kinase pathway. The effect of IGF-I was blocked by PD98059, a specific inhibitor
      of the MAP kinase-activating kinase, but not by wortmannin, a specific inhibitor
      of phosphatidylinositol 3-kinase. IGF-I inhibition of PTH/PTHrP receptor mRNA
      expression in UMR-106 cells was abrogated completely by pretreatment with
      cycloheximide, an inhibitor of protein synthesis. These findings indicate that
      IGF-I suppresses gene expression for PTH/PTHrP receptor via the MAP kinase
      pathway, and this inhibition is required for new protein synthesis in UMR-106
      osteoblast-like cells.

PMID- 9927319
TI  - Dehydroepiandrosterone: biosynthesis and metabolism in the brain.
AB  - Dehydroepiandrosterone (DHEA) is abundantly found in brain tissues of several
      species, including human. However, the cellular origin and pathway by which DHEA
      is synthesized in brain are not yet known. We have, therefore, initiated pilot
      experiments to explore gene expression of cytochrome P450 17alpha-hydroxylase
      (P450c17), the key steroidogenic enzyme for androgen synthesis, and evaluate DHEA
      production by highly purified astrocytes, oligodendrocytes, and neurons. Using RT
      PCR, we have demonstrated for the first time that astrocytes and neurons in the
      cerebral cortex of neonatal rat brain express P450c17. The presence of P450c17 in
      astrocytes and neurons was supported by the ability of these cells to metabolize
      pregnenolone to DHEA in a dose-dependent manner as determined by RIA. These data
      were further confirmed by production of androstenedione by astrocytes using
      progesterone as a substrate. However, cortical neurons express a low transcript
      of P450c17 messenger RNA and produce low levels of DHEA and androstenedione
      compared with astrocytes. Oligodendrocytes neither express the messenger RNA nor
      produce DHEA. The production of DHEA by astrocytes is not limited to cerebral
      cortex, as hypothalamic astrocytes produce DHEA at a level 3 times higher than
      that produced by cortical astrocytes. Cortical and hypothalamic astrocytes also
      have the capacity to metabolize DHEA to testosterone and estradiol in a dose
      dependent manner. However, hypothalamic astrocytes were 3 times more active than
      cortical astrocytes in the metabolism of DHEA to estradiol. In conclusion, our
      data presented evidence that astrocytes and neurons express P450c17 and
      synthesize DHEA from pregnenolone. Astrocytes also have the capacity to
      metabolize DHEA into sex steroid hormones. These data suggest that as in gonads
      and adrenal, DHEA is biosynthesized in the brain by a P450c17-dependent
      mechanism.

PMID- 9927320
TI  - Interleukin-1beta and catecholamines synergistically stimulate interleukin-6
      release from rat C6 glioma cells in vitro: a potential role for
      lysophosphatidylcholine.
AB  - Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are proinflammatory
      cytokines that affect the secretion of several neuroendocrine hormones. In
      addition, glial cells synthesize and release IL-6, suggesting a paracrine role
      for this cytokine in the brain. We have examined the regulation of IL-6 release
      from glial cells by cytokines and catecholamines. Forty ng/ml IL-1beta induced a
      maximal 30-fold stimulation of IL-6 release (P < 0.01); higher and lower
      concentrations of IL-1beta were less effective. In the presence of (Bu)2cAMP, IL
      1beta induced a strongly synergistic response with respect to IL-6 release; thus,
      the combination of these two agents resulted in a release of IL-6 that was much
      larger that the release attributed to either agent alone (i.e. 30-fold higher).
      Similarly, the combination of IL-1beta and the diterpene forskolin (but not the
      inactive analog 1,9-dideoxyforskolin) or cholera toxin also resulted in a
      synergistic stimulation of C6 glioma IL-6 release. Thus, increases in
      intracellular cAMP concentrations act in a synergistic fashion with the IL-1beta
      signaling pathway for IL-6 release. Because catecholamines increase intracellular
      cAMP levels, we investigated the effects of dopamine, epinephrine, and
      norepinephrine on IL-6 release. The combination of 1.0 to 100 microM of each
      catecholamine with IL-1beta resulted in the synergistic stimulation of IL-6
      release. The coincubation of the beta-agonist isoproterenol and IL-1beta resulted
      in a striking 25-fold synergistic induction of IL-6 release. The synergistic
      increases in IL-6 release caused by IL-1beta and isoproterenol as well as IL
      1beta and norepinephrine were blocked by the pretreatment of C6 cells with the
      beta-receptor antagonist propranolol. Because lysophosphatidylcholine (LPC) may
      function as a second messenger for IL-1beta, we also investigated the effects of
      LPC. Exogenous LPC (5 to 40 microM) stimulated IL-6 release from C6 glioma cells
      in a concentration-related manner (P < 0.01). The coincubation of LPC with
      norepinephrine provoked a synergistic release in IL-6 comparable with that
      obtained with IL-1beta and norepinephrine. Exposure of [3H]choline-labeled C6
      cells to IL-1beta resulted in an increase in the [3H]LPC species as well as a
      decrease in [3H]phosphatidylcholine. Finally, while TNF alpha was less
      efficacious than IL-1beta for the stimulation of IL-6 release from C6 cells, the
      combination of IL-1beta and TNF alpha resulted in a significant synergistic
      induction of IL-6 release. We have demonstrated that IL-1beta stimulates IL-6
      release from rat C6 glioma cells via a noncAMP-mediated mechanism that may
      involve LPC. The synergistic induction by cytokines and catecholamines of glial
      cell-derived IL-6 may subsequently affect inflammatory, neurodegenerative or
      neurotropic processes in the CNS.

PMID- 9927322
TI  - Gonadotropin-releasing hormone regulation of gonadotropin subunit gene expression
      in female rats: actions on follicle-stimulating hormone beta messenger
      ribonucleic acid (mRNA) involve differential expression of pituitary activin
      (beta-B) and follistatin mRNAs.
AB  - GnRH is the primary stimulus in the regulation of gonadotropin subunit mRNA
      expression. Additionally, local (pituitary) production of activin and follistatin
      appear to modulate the expression of FSH beta mRNA. The current studies aimed to
      determine whether GnRH regulation of pituitary activin (beta-B) and follistatin
      mRNAs could play a role in the differential actions of GnRH pulse pattern on
      gonadotropin mRNA expression in female rats. In response to altered GnRH pulse
      amplitude, the expression of FSH beta and follistatin mRNAs followed an inverse
      pattern. Only high dose GnRH increased expression of follistatin whereas, in
      contrast, beta-B and FSH beta expression were increased following lower doses of
      GnRH. To determine whether increased follistatin mRNA expression was correlated
      with FSH beta mRNA responses, we examined their temporal relationship following
      high dose GnRH. Both FSH beta and follistatin mRNAs were increased within 2 h and
      remained increased through 6 h. However, by 12 h FSH beta mRNA levels returned to
      values seen in controls, suggesting that increased follistatin requires 6-12 h to
      reduce FSH beta mRNA. In response to altered GnRH pulse frequency, FSH beta
      expression was increased at all pulse intervals (8-240 min) examined. Rapid GnRH
      pulse frequencies (8-min intervals) increased follistatin expression, whereas
      beta-B mRNA was only increased after 30-min pulse intervals, which also resulted
      in maximal FSH beta mRNA concentrations. These results suggest that changes in
      pituitary activin (beta-B) and follistatin mRNA expression may be important
      components of gonadotrope responses to pulsatile GnRH, and potentially imply that
      GnRH stimulation of activin and follistatin peptide production provides
      regulatory control over the production of FSH.

PMID- 9927321
TI  - Altered cardiac phenotype in transgenic mice carrying the delta337 threonine
      thyroid hormone receptor beta mutant derived from the S family.
AB  - The heart has been recognized as a major target of thyroid hormone action. Our
      study investigates both the regulation of cardiac-specific genes and contractile
      behavior of the heart in the presence of a mutant thyroid hormone receptor beta1
      (T3Rbeta1-delta337T) derived from the S kindred. The mutant receptor was
      originally identified in a patient with generalized resistance to thyroid
      hormone. Cardiac expression of the mutant receptor was achieved by a transgenic
      approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta)
      and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are
      known to be regulated by T3, their cardiac expression was analyzed. The messenger
      RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta
      messenger RNA was up-regulated. Although T3 levels were normal in these animals,
      this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac
      muscle contraction was significantly prolonged in papillary muscles from
      transgenic mice. The electrocardiogram of transgenic mice showed a substantial
      prolongation of the QRS interval. Changes in cardiac gene expression, cardiac
      muscle contractility, and electrocardiogram are compatible with a hypothyroid
      cardiac phenotype despite normal T3 levels, indicating a dominant negative effect
      of the T3Rbeta mutant.

PMID- 9927323
TI  - Brain-derived neurotrophic factor and neurotrophin-3 enhance somatostatin gene
      expression through a likely direct effect on hypothalamic somatostatin neurons.
AB  - Although neurotrophins (NTs) have been extensively studied as neuronal survival
      factors in some areas of the central nervous system, little is known about their
      function or cellular targets in the hypothalamus. To understand their functional
      significance and sites of action on hypothalamic neurons, we examined the effects
      of their cognate ligands on neuropeptide content and messenger RNA (mRNA)
      expression in somatostatin neurons present in fetal rat hypothalamic cultures.
      Treatments were performed in defined insulin-free medium between days 6 and 8 of
      culture, since the maximal effects of NTs on somatostatin content and mRNA
      expression were observed after 48-h incubations. Brain-derived neurotrophic
      factor and NT-3, but not nerve growth factor, induced a dose-dependent increase
      in somatostatin content, which was influenced by plating density. The same
      treatment increased somatostatin mRNA and immunostaining intensity of
      somatostatin neurons, but had no effect on the number of these labeled neurons.
      The increased levels of somatostatin (peptide and mRNA) induced by NTs were not
      blocked by tetrodotoxin or by glutamate receptor antagonists, suggesting that
      endogenous neurotransmitters (e.g. glutamate) were not involved in these effects.
      In contrast, the stimulatory effects were completely blocked by K-252a, an
      inhibitor of tyrosine kinase (Trk) receptors, whereas the less active analog K
      252b was ineffective. Double-labeling studies demonstrated that both TrkB or TrkC
      receptors were located on somatostatin neurons. Our results show that, in rat
      hypothalamic cultures, brain-derived neurotrophic factor, and NT-3 have a potent
      stimulatory effect on peptide synthesis in somatostatinergic neurons, likely
      through direct activation of TrkB and TrkC receptors.

PMID- 9927324
TI  - Maternal regulation of embryonic growth: the role of vasoactive intestinal
      peptide.
AB  - Vasoactive intestinal peptide (VIP) is an important growth regulator of the
      embryonic day (E)9-E11 mouse. In comparably aged rat embryos, VIP messenger RNA
      (mRNA) is not detectable; however, peak concentrations of VIP in maternal rat
      serum indicate a nonembryonic source. In the current study, mouse maternal and
      embryonic tissues were examined from E6-E12. Although RT-PCR revealed VIP mRNA in
      E6-E7 conceptuses, by E8 (when extraembryonic tissues could be separated from the
      embryo), VIP mRNA was detected only in the decidua/trophoblast.
      Decidual/trophoblastic VIP mRNA decreased until E10, after which it was not
      detectable. VIP mRNA was not apparent in the embryo until E11-E12. At E9, VIP
      immunoreactivity was localized to abundant, diffuse cells in the decidua basalis,
      which were also immunoreactive for T cell markers. VIP binding sites were dense
      in the decidua/trophoblast at E6, but gradually decreased until E10, after which
      they were not apparent. VIP binding sites were detected in embryonic
      neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in
      the decidua/trophoblast correlate with the critical period of VIP growth
      regulation, when VIP mRNA is absent in the embryo. These findings suggest that
      maternal lymphocytes are the source of VIP's regulating early postimplantation
      embryonic growth.

PMID- 9927325
TI  - Human osteoclast-like cells are formed from peripheral blood mononuclear cells in
      a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH
      related protein receptor gene.
AB  - Subclones of the human osteosarcoma cell line SaOS-2 were established by
      transfecting with an expression vector containing the human PTH/PTH-related
      protein (PTHrP) receptor, and their abilities to support osteoclast-like
      multinucleated cell (OCL) formation were examined in coculture with mouse or
      human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound
      high levels of [125I]-PTH and produced a significant amount of cAMP in response
      to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone
      marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also
      formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral
      blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced
      PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response
      to PTH were tartrate-resistant acid phosphatase positive, expressed abundant
      calcitonin receptors and vitronectin receptors, and formed resorption pits on
      dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3,
      prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed
      to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and
      human OCL formation supported by SaOS-4/3 cells were inhibited by either adding
      an antibody against macrophage-colony stimulating factor or adding
      granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human
      and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated.
      These results indicate that the target cells of PTH for inducing osteoclast
      formation are osteoblast/stromal cells but not osteoclast progenitor cells in the
      coculture. This coculture model will be useful for investigating the
      abnormalities ofosteoclast differentiation and function in human metabolic bone
      diseases.

PMID- 9927326
TI  - Interactions between neuropeptide Y and gamma-aminobutyric acid in stimulation of
      feeding: a morphological and pharmacological analysis.
AB  - Neuropeptide Y (NPY) produced in neurons in the arcuate nucleus and brain stem
      and released in the paraventricular nucleus (PVN) and surrounding areas is
      involved in stimulation of feeding in rats. We recently reported that gamma
      aminobutyric acid (GABA) is coexpressed in a subpopulation of NPY neurons in the
      arcuate nucleus. To determine whether GABA is colocalized in NPY terminals in the
      PVN, the site of NPY action, light and electron microscopic double staining for
      NPY and GABA using pre- and postembedding immunolabeling was performed on rat
      brain sections. GABA was detected in NPY-immunopositive axons and axon terminals
      within both the parvocellular and magnocellular divisions of the PVN. These
      morphological findings suggested a NPY-GABA interaction in the hypothalamic
      control of feeding. Therefore, the effects of muscimol (MUS), a GABA(A) receptor
      agonist, on NPY-induced food intake were examined in sated rats. When injected
      intracerebroventricularly, both NPY and MUS elicited dose-dependent feeding
      responses that were blocked by the administration of 1229U91 (a putative Y1
      receptor antagonist) or bicuculline (a GABA(A) receptor antagonist),
      respectively. Coadministration of NPY and MUS intracerebroventricularly amplified
      the feeding response over that evoked by NPY or MUS alone. Similarly,
      microinjection of either NPY or MUS into the PVN stimulated food intake in a dose
      related fashion, and coinjection elicited a significantly higher response than
      that evoked by either individual treatment. These results suggest that GABA and
      NPY may coact through distinct receptors and second messenger systems in the PVN
      to augment food intake.

PMID- 9927327
TI  - Requirement for phosphatidylinositol-3'-kinase in cytokine-mediated germ cell
      survival during fetal oogenesis in the mouse.
AB  - Apoptosis is responsible for primordial germ cell (PGC) attrition in the
      developing fetal ovary. In monolayer cultures of murine PGC, stem cell factor
      (SCF) and leukemia inhibitory factor (LIF) independently promote survival in
      vitro; however, the relevance of these data to fetal ovarian oogonium and oocyte
      survival, as well as the intracellular events involved in transducing the
      antiapoptotic actions of these cytokines in germ cells, remain to be elucidated.
      In this report, we investigated the effects of SCF and LIF, alone and in
      combination, on the survival of oogonia and oocytes, and elaborated on components
      of the signal transduction pathway used by these molecules, after validating a
      method of culturing fetal mouse ovaries. We further employed this system to also
      test the hypothesis that insulin-like growth factor-I (IGF-I), a classic
      antiapoptotic molecule, and transforming growth factor-beta (TGF-beta), a classic
      pro-apoptotic molecule, interact with the SCF/LIF pathway and function in a
      reciprocal fashion to precisely regulate germ cell numbers during fetal
      oogenesis. Freshly isolated embryonic day 13.5 ovaries contained nonapoptotic
      germ cells, as determined by histologic analysis of cellular morphology and in
      situ 3'-end-labeling of DNA integrity. In vitro culture of fetal ovaries without
      tropic support for 24, 48, and 72 h resulted in a time-dependent induction of
      germ cell apoptosis, such that most oogonia and oocytes present after 72 h were
      apoptotic. Morphometric analysis of serially sectioned ovaries indicated that the
      numbers of nonapoptotic germ cells remaining after 24, 48, and 72 h of culture
      were 78%, 38%, and 10%, respectively, of the number present before culture (P <
      0.05 for all time points vs. 0 h). Inclusion of SCF (100 ng/ml) together with LIF
      (100 ng/ml) in the culture medium significantly attenuated germ cell apoptosis,
      with the SCF/LIF-treated ovaries retaining 5.5-fold more oogonia and oocytes
      after 72 h of culture as compared with control ovaries deprived of tropic support
      (P < 0.05). However, SCF or LIF, when added separately, had no (SCF) or little
      (LIF) inhibitory effect on germ cell apoptosis. Provision of 50 ng/ml IGF-I
      maintained survival of approximately two-thirds of the germ cells in cultured
      ovaries (P < 0.05), whereas a combination of all three growth factors (SCF, LIF,
      IGF-I) completely preserved the fetal ovary in culture to that resembling a
      freshly-isolated gonad. Cotreatment with 25 ng/ml TGF-beta partially reversed the
      survival actions of IGF-I or SCF/LIF, such that only one-third of the starting
      number of oogonia/oocytes remained after 72 h of culture (P < 0.05). Lastly, the
      antiapoptotic effects of SCF/LIF or IGF-I were almost entirely eliminated by
      cotreatment of fetal ovaries with either one of two inhibitors of
      phosphatidylinositol-3'-kinase (PI3K), LY294002 (5 microM) or wortmannin (50 nM),
      whereas cotreatment with an inhibitor of p70 S6 kinase (rapamycin, 25 ng/ml) was
      without effect. These data indicate that the combined actions of SCF, LIF, and
      IGF-I are required for maximal inhibition of apoptosis in germ cells of fetal
      mouse ovaries, and that the PI3K signaling pathway is an essential component of
      cytokine-mediated female germ cell survival. Moreover, TGF-beta can partially
      override the antiapoptotic actions of SCF/LIF or IGF-I in oogonia and oocytes,
      suggesting the existence of a complex signaling network that ultimately
      determines fetal ovarian germ cell fate.

PMID- 9927329
TI  - Determinants of spatial polarity in the growth plate.
AB  - Growth of long bones occurs at the growth plate, a layer of cartilage that
      separates the epiphysis from the metaphysis. Growth plate exhibits spatial
      polarity. Proliferative chondrocytes undergo terminal differentiation when they
      approach the metaphyseal, but not the epiphyseal, border of the growth plate. The
      adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal,
      blood vessels and bone cells invade the adjacent growth plate, remodeling it into
      bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To
      determine whether cartilage polarity determines bone polarity and/or whether bone
      polarity determines cartilage polarity, rabbit distal ulnar growth plates were
      excised, inverted, and reimplanted in their original beds. Thus, cartilage
      polarity was inverted relative to bone polarity. Histological examination showed
      that the inverted cartilage polarity was maintained over time. In contrast, the
      polarity of the adjacent bone reversed after surgery, to match that of the
      cartilage. Blood vessel and bone cell invasion ceased in the metaphysis and arose
      in the epiphysis. Longitudinal bone growth (measured with weekly radiographs)
      occurred at the epiphyseal, not at the metaphyseal, surface of the growth plate.
      We conclude that the polarity of growth plate cartilage is determined by
      intrinsic factors. The cartilage polarity then determines the polarity of the
      adjacent bone and, consequently, the functional polarity of longitudinal bone
      growth.

PMID- 9927328
TI  - Characterization of an intrinsically fluorescent gonadotropin-releasing hormone
      receptor and effects of ligand binding on receptor lateral diffusion.
AB  - The GnRH receptor (GnRHR) is a G protein-coupled receptor expressed by
      gonadotropes in the anterior pituitary gland. In the past several years, much has
      been learned about the structure-function relationships that exist in this
      receptor with regard to ligand binding and signal transduction. However, the lack
      of specific antibodies has precluded any analyses of the behavior of the unbound
      form of this receptor. We have constructed a functional GnRHR in which enhanced
      green fluorescent protein is fused to the carboxyl-terminus of the murine GnRHR.
      This fusion receptor was expressed diffusely throughout the cell, with
      approximately 38% of the fusion receptors colocalized with a plasma membrane
      marker in the gonadotrope-derived alphaT3 cell line, and approximately 82% of the
      fusion receptors colocalized with a membrane marker in Chinese hamster ovary
      cells. Furthermore, the fusion receptor displayed a Kd of 0.8 nM for iodinated
      des-Gly10,D-Ala-6-GnRH N-ethyl amide in Chinese hamster ovary cells, which was
      similar to the Kd of the native GnRHR expressed in alphaT3 cells. The surface
      mobility of the fusion protein was examined by fluorescence photobleaching
      recovery methods. In the unbound state the majority of the receptors were
      laterally mobile and displayed a lateral diffusion rate of 1.2-1.6 x 10(-9)
      cm2/sec. Binding of GnRH reduced the rate of lateral diffusion over 3-fold and
      reduced the fraction of mobile receptors from approximately 76-91% to 44-61%.
      Like GnRH, the competitive GnRH antagonist antide slowed the rate of receptor
      diffusion approximately 3-fold. In contrast to GnRH, antide had no effect on the
      fraction of mobile receptors. Thus, an intrinsically fluorescent GnRHR is
      trafficked to the plasma membrane of mammalian cells, is capable of ligand
      binding and signal transduction, and allows direct observation of the GnRHR in
      the nonligand-bound state. Furthermore, fluorescence photobleaching recovery
      analysis of the GnRHR-green fluorescent protein fusion reveals fundamental
      differences in the membrane dynamics of the GnRHR induced by the binding of an
      agonist vs. that induced by the binding of an antagonist.

PMID- 9927330
TI  - Differential expression of estrogen receptor-beta and estrogen receptor-alpha in
      the rat ovary.
AB  - Immunohistochemical localization of two estrogen receptor (ER) subtypes, ER beta
      and ER alpha, was performed in neonatal, early postnatal, immature, and adult
      rats to determine whether ER alpha and ER beta are differentially expressed in
      the ovary. ER beta and ER alpha were visualized using a polyclonal anti-ER beta
      antibody and a monoclonal ER alpha (ID5) antibody, respectively. Postfixed frozen
      sections and antigen-retrieved paraffin sections of the ovary revealed nuclear ER
      beta immunoreactivity (IR) in granulosa cells, which was prevented when peptide
      adsorbed antibody was used instead. In immature and adult rat ovaries, ER beta
      was expressed exclusively in nuclei of granulosa cells of primary, secondary, and
      mature follicles. Atretic follicle granulosa cells showed only weak or no
      staining. No specific nuclear ER beta IR was detected in thecal cells, luteal
      cells, interstitial cells, germinal epithelium, or oocytes. In neonatal rat
      ovary, no ER beta expression was found. In ovaries of 5- and 10-day-old rats,
      weak ER beta IR was observed in granulosa cells of primary and secondary
      follicles, but no staining was detected in the primordial follicles. ER alpha
      protein exhibited a differential distribution in the ovary with no detectable
      expression in the granulosa cells but evidence of ER alpha IR in germinal
      epithelium, interstitial cells, and thecal cells. In the oviduct and uterus, IR
      for ER alpha, but not ER beta, was found in luminal epithelium, stromal cells,
      muscle cells, and gland cells. Our present study demonstrates that ER beta and ER
      alpha proteins are expressed in distinctly different cell types in the ovary. The
      exclusive presence of ER beta in granulosa cells implies that this specific new
      subtype of ER beta mediates some effects of estrogen action in the regulation of
      growth and maturation of ovarian follicles.

PMID- 9927331
TI  - Ovine arylalkylamine N-acetyltransferase in the pineal and pituitary glands:
      differences in function and regulation.
AB  - The enzyme arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) has been
      conventionally linked with the biosynthesis of melatonin within the pineal gland
      and retina. This study establishes that AANAT messenger RNA (mRNA) and functional
      enzyme occurs within the pars tuberalis (PT) and to a lesser degree within the
      pars distalis (PD) of the sheep pituitary gland; expression in these tissues is
      approximately 1/15th (PT) and 1/300th (PD) of that in the ovine pineal gland.
      AANAT mRNA in the PT appears to be expressed in the same cells as the Mel1a
      receptor. No evidence was obtained to indicate that either PT or PD cells have
      the ability to synthesize melatonin, suggesting that this enzyme plays a
      different functional role in the pituitary. We also found that cAMP regulation of
      the abundance of AANAT mRNA differs between the PT and pineal gland. Forskolin
      (10 microM) has no effect on pineal AANAT mRNA levels, yet represses expression
      in the PT. This suppressive influence could be mediated by ICER (inducible cAMP
      response early repressor), which is induced by forskolin in both tissues.
      Although it appears that the specific function and regulation of AANAT in the
      pituitary gland differ from that in the pineal gland, it seems likely that AANAT
      may play a role in the broader area of signal transduction through the
      biotransformation of amines.

PMID- 9927332
TI  - Differential localization of inhibin subunit proteins in the ovine testis during
      fetal gonadal development.
AB  - Inhibins and activins are dimeric proteins that are involved in cell
      proliferation, apoptosis, and differentiation in a number of systems and have
      previously been detected in fetal testes of many species. This study used
      immunohistochemistry to examine the localization of inhibin alpha-, betaA-, and
      betaB- subunits during ovine testicular development from days 40-135 of
      gestation. Localization of inhibin betaA- and betaB-subunit messenger RNAs was
      confirmed by in situ hybridization. The results showed that there was
      differential localization of inhibin alpha-, betaA-, and betaB-subunits to
      specific cells in the ovine fetal testis from 40 days of gestation. All three
      inhibin subunits were present in Sertoli cells throughout gestation, whereas the
      rete epithelium and gonocytes did not express inhibin alpha-subunit. These data
      suggest that the fetal Sertoli cells have the capacity to produce all forms of
      inhibins and activins, i.e. inhibin A and B, and activins A, AB, and B, whereas
      the rete testis epithelial cells can only synthesize activin A. In the
      interstitium, the fetal Leydig cells expressed all three inhibin subunits, but
      this was restricted to the period between 40 and 90 days of gestation.
      Thereafter, inhibin alpha-subunit immunoreactivity was not observed in fetal
      Leydig cells, which suggests that only activin ligands are produced by Leydig
      cells during late gestation. Collectively, the data demonstrate that fetal ovine
      testes have the potential to produce the full repertoire of inhibins and activins
      from very early in testicular differentiation. The distinct and restricted
      localization of the various subunits to specific cells suggests that specific
      dimeric proteins have particular roles in the development and function of the
      fetal testis.

PMID- 9927333
TI  - Inhibition of Zac1, a new gene differentially expressed in the anterior
      pituitary, increases cell proliferation.
AB  - Zac1 is a new zinc finger protein that concomitantly controls apoptosis and cell
      cycle arrest through separate pathways. The mouse Zac1 gene is mainly expressed
      in the pituitary gland and in different brain areas. In this study regional and
      cellular expression of Zac1 in the pituitary gland was determined by in situ
      hybridization. Zac1 messenger RNA was abundantly expressed in the anterior
      pituitary lobe compared with that in the intermediate and posterior lobes. Zac1
      transcripts were found in all hormone-secreting cell types, with the highest
      levels in GH- and PRL-producing cells. To investigate the impact of Zac1 in
      pituitary cell proliferation, we ablated the endogenous Zac1 gene by antisense
      treatment in two murine cell types, AtT-20 and TtT/GF, that are representative of
      granular and agranular cell lineages, respectively. The decline in Zac1 protein
      levels under antisense treatment was accompanied by increased DNA synthesis in
      clonal corticotroph and folliculo-stellate cells, as demonstrated by enhanced
      [3H]thymidine incorporation (36% and 50%, respectively). Antisense
      oligonucleotides against Zac1 controlled cell proliferation in a dose-dependent
      way, and mutagenized antisense oligonucleotides were inert. Conclusively, our
      data provide the first evidence of a role for Zac1 in pituitary growth control.

PMID- 9927334
TI  - Insulin-like growth factor binding protein-1 expression in baboon endometrial
      stromal cells: regulation by filamentous actin and requirement for de novo
      protein synthesis.
AB  - Stromal fibroblasts in the primate endometrium undergo dramatic morphological and
      biochemical changes in response to pregnancy. This transformation is
      characterized by the expression of insulin-like growth factor binding protein-1
      (IGFBP-1). Stromal cells from the baboon endometrium of nonpregnant animals were
      cultured and subsequently treated with cytochalasin D to disrupt actin filaments.
      In response to cytochalasin D treatment, cells contracted and became rounded as
      early as 10 min after the initiation of treatment. When cytochalasin D was
      removed, cells reverted back to their original fibroblastic shape within 1 h.
      After cells were treated with cytochalasin D for 5 h, addition of (Bu)2cAMP
      and/or hormones (estradiol, medroxyprogesterone acetate, and relaxin) resulted in
      the expression of IGFBP-1 messenger RNA and protein within 24 h. Cells with an
      intact cytoskeleton did not express detectable levels of IGFBP-1 in response to
      hormones and/or (Bu)2cAMP. Furthermore, the addition of cycloheximide inhibited
      expression of IGFBP-1 in cytochalasin D-treated cells. Stromal cells were also
      isolated from early pregnant and simulated pregnant animals. Within 48 h, cells
      from both the pregnant and simulated pregnant animals produced IGFBP-1 in
      response to hormones and/or (Bu)2cAMP. In these studies, IGFBP-1 expression was
      also inhibited by cycloheximide. These studies suggest that induction of IGFBP-1
      requires an intermediary protein and that alterations in the cytoskeleton may be
      involved.

PMID- 9927335
TI  - Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its
      binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR
      knockout mice.
AB  - Previous studies have shown that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays
      important roles in the formation of osteoclasts through its actions on
      osteoblastic cells. We have generated mice lacking vitamin D receptor (VDR) by
      gene targeting (VDR-/-). These mice had tartrate-resistant acid phosphatase
      (TRAP)-positive osteoclasts, and exhibited similar levels of parameters for bone
      resorption to those in wild type mice. The present studies were undertaken to
      clarify whether effects of 1,25(OH)2D on osteoclast formation require VDR in
      osteoblasts, and to examine mechanisms of the formation of osteoclasts without
      VDR-mediated actions using VDR-/- mice. When wild-type calvarial osteoblasts and
      spleen cells were co-cultured with 1,25(OH)2D, TRAP-positive osteoclasts were
      formed regardless of the genotypes of spleen cells. In contrast, when osteoblasts
      from VDR-/- mice were co-cultured, no osteoclasts could be formed even with wild
      type spleen cells. Parathyroid hormone and interleukin-1alpha stimulated
      osteoclast formation by co-cultures from VDR-/- mice, and the generated
      osteoclasts showed resorbing activity. These results demonstrate that VDR
      mediated actions of 1,25(OH)2D in osteoblasts are essential for osteoclast
      formation by 1,25(OH)2D, and that functionally intact osteoclasts can be formed
      without 1,25(OH)2D actions under stimulations by other agents. It is suggested
      that osteoclastic bone resorption can be maintained without 1,25(OH)2D actions by
      other stimulatory agents.

PMID- 9927336
TI  - Daily melatonin administration at middle age suppresses male rat visceral fat,
      plasma leptin, and plasma insulin to youthful levels.
AB  - Human and rat pineal melatonin secretion decline with aging, whereas visceral fat
      and plasma insulin levels increase. Melatonin modulates fat metabolism in some
      mammalian species, so these aging-associated melatonin, fat and insulin changes
      could be functionally related. Accordingly, we investigated the effects of daily
      melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10
      months) and continuing into old age (22 months). Melatonin was added to the
      drinking water (92% of which was consumed at night) at a dosage (4 microg/ml)
      previously reported to attenuate the aging-associated decrease in survival rate
      in male rats, as well as at a 10-fold lower dosage. The higher dosage produced
      nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher
      than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged
      rats receiving the lower dosage were not significantly different from young or
      middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat,
      as well as plasma insulin and leptin levels, were all significantly increased at
      middle age when compared to young rats. All were restored within 10 weeks to
      youthful (4 month) levels in response to both dosages of melatonin. Continued
      treatment until old age maintained suppression of visceral (retroperitoneal +
      epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels
      were not significantly altered by aging or melatonin treatment. Plasma
      testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine
      (T3) decreased by middle age; these aging-associated decreases were not
      significantly altered by melatonin treatment. Thus, visceral fat, insulin and
      leptin responses to melatonin administration may be independent of marked changes
      in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral
      fat is associated with increased insulin resistance, diabetes, and cardiovascular
      disease, these results suggest that appropriate melatonin supplementation may
      potentially provide prophylaxis or therapy for some prominent pathologies
      associated with aging.

PMID- 9927337
TI  - CRF type I receptor-deficient mice exhibit a pronounced pituitary-adrenal
      response to local inflammation.
AB  - Recent studies indicate that the regulation of adrenocorticotropin (ACTH)
      secretion by corticotropin-releasing factor (CRF) is mediated predominantly by
      the type I CRF receptor (CRF-R1). Indeed, CRF-R1-deficient (CRF-R1 -/-) mice show
      marked impairment of the pituitary-adrenal axis. However, the plasma ACTH
      concentrations of unstressed CRF-R1 -/- mice are similar to those in wild-type
      mice. We show here that arginine vasopressin (AVP) is a major ACTH secretagogue
      in CRF-R1 -/- mice in resting conditions, since administration of anti-AVP serum,
      but not anti-CRF serum, markedly reduced (by 60%) resting plasma ACTH
      concentrations in these mutants. We also investigated the pituitary-adrenal
      response to turpentine-induced local inflammation in CRF-R1 -/- mice.
      Administration of turpentine into the hind-limb of CRF-R1 -/- mice produced a
      slightly (15-25%) smaller swelling of the limb, but a 10 fold greater rise in
      plasma IL-6 levels, compared to CRF-R1 +/+ controls. Turpentine-induced local
      inflammation produced pronounced elevations in the plasma concentrations of both
      ACTH and corticosterone in both CRF-R1 -/- and wild-type mice, but ACTH secretion
      could be inhibited by anti-CRF and anti-AVP sera only in wild-type mice. These
      data indicate that resting ACTH secretion in CRF-R1 -/- mice is in part
      attributable to AVP-dependent mechanisms. Furthermore, while in normal mice the
      pituitary-adrenal response to local inflammation is mediated largely via CRF
      dependent mechanisms, mice deficient in CRF-R1 are still able to mount a
      pituitary-adrenal response via mechanisms that do not depend critically on either
      CRF or AVP action.

PMID- 9927338
TI  - Expression of cytokine messenger ribonucleic acids in the bovine corpus luteum.
AB  - There is considerable evidence that luteolysis in the cow and other species
      involves components of the immune system. In this study, we examined the
      expression of the mRNAs for TNF-alpha, IFN-gamma, IL-1beta, IL-2, and IL-2
      receptor (IL-2R) by reverse transcription-polymerase chain reaction (RT-PCR)
      using bovine-specific primers. Expression was examined in corpora lutea (CL) of
      the early (day 5), mid (days 11-12), and late (day 18) luteal phase, and at 1, 4,
      and 24 hours following a luteolytic dose of prostaglandin (PG) F2alpha. Tumor
      necrosis factor-alpha, IFN-gamma, and IL-1beta mRNAs were detectable by RT-PCR at
      all stages of the cycle examined. Densitometric intensities of the
      electrophoresed IFN-gamma PCR products revealed a drop in RNA expression during
      late diestrus and at one hour of prostaglandin-induced luteolysis (P < 0.05). The
      mRNA for TNF-alpha seemed to remain constant during the cycle, and rose slightly
      during luteolysis. Interleukin-1beta mRNA also did not vary during the cycle or
      during luteolysis. Finally, expression of mRNAs for IL-2 and IL-2 receptor was
      not evident in CL by the methods employed in this study. These results are the
      first to describe mRNA expression for TNF-alpha, IFN-gamma, and IL-1beta in the
      bovine corpus luteum, and support a role for these cytokines in luteal function
      and regression.

PMID- 9927339
TI  - Cloning of a 5.8 kb cDNA for a mouse type 2 deiodinase.
AB  - From studies with their cDNAs, the types 1 and 3 deiodinases (D1 and D3) have
      been shown unequivocally to be selenoproteins. Studies with recently cloned cDNAs
      for the mammalian type 2 deiodinase (D2) indicate that they also code for
      selenoproteins. However, these D2 cDNAs are not full length and they do not
      contain an essential selenocysteine insertion sequence (SECIS) in their 3'UTR; a
      heterologous SECIS had to be ligated to the coding region before expression of
      the D2 could be achieved. Thus their role as cDNAs for the native D2 is open to
      question. We now report the cloning of a 5.8 kb cDNA for the mouse D2. This cDNA
      contains a SECIS in its 3'UTR located more than 4.5 kb from the coding region.
      When the mRNA transcribed in vitro from this cDNA is injected into X. laevis
      oocytes, a deiodinase with characteristics of D2 is expressed.

PMID- 9927341
TI  - Martin tobin, editor-designate 

PMID- 9927340
TI  - Heparin-binding property of human prolactin: a novel aspect of prolactin biology.
AB  - Prolactin (PRL) shares several characteristics with growth factors and cytokines,
      many of which are known to bind to heparan sulfate proteoglycans. In this study
      we examined the heparin-binding properties of selected members of the PRL/GH
      family, using heparin affinity columns followed by gel electrophoresis/Western
      blotting. Purified human PRL and its cleaved 16K fragment, but not human GH or
      placental lactogen, were retained on the heparin column and were displaced by 0.5
      M NaCl. Native PRL in human pituitary extracts and amniotic fluid showed a
      similar binding affinity to heparin as the purified hormone. None of the other
      hormones tested, e.g., rat, ovine and bovine PRL, glycosylated ovine PRL or rat
      GH, bound to heparin. Two consensus heparin-binding sequences are present in
      human PRL but not in the other hormones included in this study. We postulate that
      the heparin-binding capability of PRL affects its biological activity as a growth
      factor and the angiostatic actions of its 16K fragment.

PMID- 9927342
TI  - All but quiet on the particulate front.

PMID- 9927343
TI  - A prospective clinical trial of pulse therapy with glucocorticoid and
      cyclophosphamide in moderate to severe paraquat-poisoned patients.

PMID- 9927344
TI  - Role of hemodynamics in pulmonary vascular remodeling: implications for primary
      pulmonary hypertension.

PMID- 9927345
TI  - Oxygen saturation, pulse rate, and particulate air pollution: A daily time-series
      panel study.
AB  - Although epidemiological studies have linked particulate air pollution with
      cardiopulmonary mortality, underlying biological mechanisms remain largely
      unknown. Unexplored pathophysiological pathways include transient declines in
      blood oxygenation and/or changes in cardiac rhythm following particulate
      exposure. In this study, blood oxygen saturation using pulse oximetry (SpO2) and
      pulse rate were measured daily on a panel of 90 elderly subjects during the
      winter of 1995-1996 in Utah Valley. Associations of SpO2 and pulse rate with
      respirable particulate pollution (particles with an aerodynamic diameter </= a
      nominal 10 microm [PM10]) were evaluated. SpO2 was not consistently associated
      with PM10. Pulse rate and the odds of the pulse rate being elevated by 5 or 10
      beats per minute (beats/min) were associated with PM10 on the previous 1 to 5 d.
      A 100 microg/m3 increase in previous-day PM10 was associated with an average
      increase of 0.8 beats/min and 29 and 95% increased odds of the pulse rate being
      elevated by 5 or 10 beats/min, respectively. Although there was little evidence
      of pollution-related hypoxia, alterations in pulse rate could reflect cardiac
      rhythm changes and may be part of the pathophysiology linking particles to
      cardiopulmonary mortality. The observed lag structure is consistent with
      particulate-induced pulmonary inflammation and cytokine release, but the
      biological relevance requires further study.

PMID- 9927346
TI  - Long-term inhalable particles and other air pollutants related to mortality in
      nonsmokers.
AB  - Long-term ambient concentrations of inhalable particles less than 10 microm in
      diameter (PM10) (1973- 1992) and other air pollutants-total suspended sulfates,
      sulfur dioxide, ozone (O3), and nitrogen dioxide-were related to 1977-1992
      mortality in a cohort of 6,338 nonsmoking California Seventh-day Adventists. In
      both sexes, PM10 showed a strong association with mortality for any mention of
      nonmalignant respiratory disease on the death certificate, adjusting for a wide
      range of potentially confounding factors, including occupational and indoor
      sources of air pollutants. The adjusted relative risk (RR) for this cause of
      death as associated with an interquartile range (IQR) difference of 43 d/yr when
      PM10 exceeded 100 microg/m3 was 1.18 (95% confidence interval [CI]: 1.02, 1.36).
      In males, PM10 showed a strong association with lung cancer deaths-RR for an IQR
      was 2.38 (95% CI: 1.42, 3.97). Ozone showed an even stronger association with
      lung cancer mortality for males with an RR of 4.19 (95% CI: 1.81, 9.69) for the
      IQR difference of 551 h/yr when O3 exceeded 100 parts per billion. Sulfur dioxide
      showed strong associations with lung cancer mortality for both sexes. Other
      pollutants showed weak or no association with mortality.

PMID- 9927347
TI  - Changes in the work of breathing induced by tracheotomy in ventilator-dependent
      patients.
AB  - Tracheotomy is widely performed on ventilator-dependent patients, but its effects
      on respiratory mechanics have not been studied. We measured the work of breathing
      (WOB) in eight patients before and after tracheotomy during breathing at three
      identical levels of pressure support (PS): baseline level (PS-B), PS + 5 cm H2O
      (PS+5), and PS - 5 cm H2O (PS-5). After the procedure, we also compared the
      resistive work induced by the patients' endotracheal tubes (ETTs) and by a new
      tracheotomy cannula in an in vitro bench study. A significant reduction in the
      WOB was observed after tracheotomy for PS-B (from 0.9 +/- 0.4 to 0.4 +/- 0.2 J/L,
      p < 0.05), and for PS-5 (1.4 +/- 0.6 to 0.6 +/- 0.3 J/L, p < 0.05), with a near
      significant reduction for PS+5 (0.5 +/- 0.5 to 0.2 +/- 0.1 J/L, p = 0.05). A
      significant reduction was also observed in the pressure-time index of the
      respiratory muscles (181 +/- 92 to 80 +/- 56 cm H2O. s/min for PS-B, p < 0.05).
      Resistive and elastic work computed from transpulmonary pressure measurements
      decreased significantly at PS-B and PS-5. A significant reduction in occlusion
      pressure and intrinsic positive end-expiratory pressure (PEEP) was also observed
      for all conditions, with no significant change in breathing pattern. Three
      patients had ineffective breathing efforts before tracheotomy, and all had
      improved synchrony with the ventilator after the procedure. In vitro measurements
      made with ETTs removed from the patients, with new ETTs, and with the tracheotomy
      cannula showed that the cannula reduced the resistive work induced by the
      artificial airway. Part of these results was explained by a slight, subtle
      reduction of the inner diameter of used ETTs. We conclude that tracheotomy can
      substantially reduce the mechanical workload of ventilator-dependent patients.

PMID- 9927348
TI  - Partitioning of respiratory system resistance in children with respiratory
      insufficiency.
AB  - Using end-inspiratory airway occlusion, respiratory system resistance (Rrs) can
      be partitioned into a flow-resistive component (Rint), and an additional
      component (DeltaR), reflecting viscoelasticity and time constant inequalities. We
      studied flow and volume dependence of Rrs and its subdivisions (Rint and DeltaR)
      in 13 children, seven mechanically ventilated for pulmonary insufficiency (Group
      1; six with parenchymal lung disease; one with lower airway obstruction) and six
      without primary lung disorder (Group 2). In comparison with healthy children,
      Rint was increased in the patient with lower airway obstruction and five of six
      patients without primary lung disorder but in only one of six with parenchymal
      lung disease. DeltaR was increased in all seven patients in Group 1 and in four
      of six patients in Group 2. The directions of changes in Rint and Rrs with
      increasing flow (isovolume conditions) and with increasing volume (isoflow
      conditions) were variable. DeltaR decreased exponentially (p < 0.05) with
      increasing flow in 11 of 13 subjects and increased with increasing tidal volume
      (VT) in 12 of 13. Thus, DeltaR was increased in most children on mechanical
      ventilation with or without primary lung disease; its volume and flow dependence
      were opposite to that of airway resistance.

PMID- 9927350
TI  - Impaired airway function and wheezing in infancy: the influence of maternal
      smoking and a genetic predisposition to asthma.
AB  - This prospective community-based study of infants born in inner London was
      undertaken to examine the association between premorbid airway function and
      subsequent wheezing in the first year of life and to explore the influence on
      this association of a family history of asthma and maternal smoking during
      pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and
      physician-diagnosed wheezing episodes were identified retrospectively from
      medical records. Specific airway conductance was determined from plethysmographic
      measurements of lung volume and airway resistance, before 13 wk and prior to any
      respiratory illness, in 101 infants, 28 of whom experienced at least one episode
      of wheezing during the first year. Mean (SD) specific airway conductance was
      significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s-1.
      kPa-1 and 2.60 (0.93) s-1. kPa-1, respectively (p < 0.05), and in those with a
      first-degree relative with asthma: 1.98 (0.83) s-1. kPa-1 and 2.60 (1.0) s-1. kPa
      1, respectively (p < 0.05), but not in those whose mothers smoked during
      pregnancy, in whom airway resistance was, however, significantly elevated (p <
      0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to
      3.8) for every unit (s-1. kPa-1) decline in specific airway conductance (p =
      0.02). After adjustment for premorbid airway function, the odds of wheezing were
      significantly increased in those with a family history of asthma (4. 3; 95% CI,
      1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy
      (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that
      impaired premorbid airway function precedes and predicts wheezing in the first
      year. Among those with a genetic predisposition to asthma, alterations in airway
      geometry or tone may increase susceptibility to wheezing. Maternal smoking has
      important and potentially preventable adverse effects on somatic growth and
      respiratory morbidity in early life.

PMID- 9927349
TI  - Acidosis stimulates nitric oxide production and lung damage in rats.
AB  - Systemic hypotension during sepsis is thought to be due to nitric oxide (NO)
      overproduction, but it may also be due to acidosis. We evaluated in healthy rats
      the consequences of acid infusion on NO and blood pressure. Sprague-Dawley rats
      were anesthetized, and ventilated with room air. The animals were randomized into
      four groups. Group 1 (C, n = 10) received only normal saline at rates comparable
      to the other groups. Group 2 (A1, n = 10) received hydrochloric acid at 0.162
      mmol in the first 15 to 30 min, followed by a continuous infusion of 0.058 mmol/h
      for 5 h. Group 3 (AG+A1, n = 6) was pretreated with aminoguanidine (AG, 50
      mg/kg), and HCl was infused as above. Group 4 (A2, n = 7) received HCl at twice
      the rate used in A1. Nitric oxide concentration in the exhaled gas (ENO), blood
      gases, and mean arterial pressure were measured every 30 min. Acid infusion in A1
      caused the pH to fall gradually from 7.43 +/- 0. 01 to 7.13 +/- 0.05. This
      moderate decrease in pH was associated with a marked increase in ENO (1.6 +/- 0.3
      to 114.2 +/- 22.3 ppb), an increase in plasma nitrite/nitrate (17.3 +/- 3.7 to
      35.2 +/- 4.3 microM), and a significant decrease in blood pressure (110.5 +/- 6.3
      to 63.3 +/- 15.0 mm Hg). Furthermore, acidosis caused lung inflammation, as
      suggested by the increase in lung myeloperoxidase activity (282.2 +/- 24.7 to
      679.3 +/- 57.3 U/min/g) and lung injury score (1.7 +/- 0.2 to 3.5 +/- 0.6).
      Acidosis after AG pretreatment was associated with a similar change in pH, but
      the increase in ENO, nitrite/nitrate, and systemic hypotension were prevented.
      Furthermore, lung injury was attenuated by AG, as suggested by a lower
      myeloperoxidase activity, though lung injury score was not altered. In this
      model, moderate acidosis causes increases in NO, hypotension, and lung
      inflammation. Lung inflammation and injury are due in part to acidosis and NO
      production. This is the first report to show a direct effect of chronic acidosis
      on NO production and lung injury. These results have profound implications on the
      role of acidosis on NO production and lung injury during sepsis.

PMID- 9927351
TI  - Normal lung function in subjects heterozygous for surfactant protein-B
      deficiency.
AB  - Inherited deficiency of surfactant protein-B (SP-B) is a fatal autosomal
      recessive disorder of lung cell metabolism caused most frequently by a frameshift
      mutation in codon 121 of the SP-B gene (121ins2) and is characterized by rapidly
      progressive respiratory failure immediately after birth. Lungs from genetically
      engineered heterozygous SP-B-deficient mice exhibit decreased compliance and mild
      air trapping. To determine whether pulmonary function of heterozygous SP-B
      deficient humans is similarly affected, we studied nine heterozygous subjects 16
      to 44 yr of age and two unaffected subjects 7 and 23 yr of age from five families
      of 121ins2 SP-B-deficient infants. An increase in residual volume was noted in
      one heterozygous family member and one unaffected family member. Compliance,
      maximal transpulmonary pressure, air flow, and gas exchange were normal in all
      heterozygous subjects tested. These data suggest that humans heterozygous for the
      121ins2 mutation have normal pulmonary function through the first four decades of
      life. The impact of advancing age and environmental exposures on the lung
      function of heterozygotes remains to be determined.

PMID- 9927352
TI  - Demographic and anthropometric correlates of maximum inspiratory pressure: The
      Atherosclerosis Risk in Communities Study.
AB  - Maximum inspiratory pressure (MIP), an indicator of inspiratory muscle strength,
      is reported on 13,005 African-American and white participants from the
      Atherosclerosis Risk in Communities Study. Sex-specific associations between MIP
      and age, anthropometric measures, physical activity, health status, smoking
      status, and education level are presented. In this cohort of subjects 47 to 68 yr
      of age, MIP decreased 0.93 cm H2O (p </= 0.0001) in women and 1.2 cm H2O (p </=
      0.0001) in men for each 1-yr increase in age. In both sexes, after adjusting for
      age, the associations between MIP and current body weight, weight at 25 yr of
      age, waist girth, body mass index, and calf girth were statistically significant
      and nonlinear (convex quadratic). MIP was positively associated with standing
      height in both sexes after controlling for age (p </= 0.03). The age-adjusted
      association between MIP and sitting height was nonlinear in men and linear in
      women. MIP was also associated (positively) with education level, health status,
      physical activity, and (negatively) cigarette smoking. The study was not designed
      to evaluate associations with race, but data patterns suggest the absence of a
      race effect on MIP.

PMID- 9927353
TI  - Involvement of tachykinin NK1 receptor in the development of allergen-induced
      airway hyperreactivity and airway inflammation in conscious, unrestrained guinea
      pigs.
AB  - It has been suggested that tachykinin NK1 receptor-mediated neurogenic
      inflammation, characterized by microvascular leakage, mucus secretion, and
      infiltration and activation of inflammatory cells in the airways, may be involved
      in allergic asthma. Therefore, in a guinea pig model of allergic asthma, we
      investigated the involvement of the NK1 receptor in allergen-induced early (EAR)
      and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these
      reactions and airway inflammation, using the selective nonpeptide NK1 receptor
      antagonist SR140333. On two different occasions, separated by 1 wk interval, OA
      sensitized guinea pigs inhaled either saline (3 min) or SR140333 (100 nM, 3 min)
      at 30 min before as well as at 5.5 h after OA provocation (between the EAR and
      LAR) in a random crossover design. A control group, receiving saline inhalations
      before and at 5.5 h after the two OA provocations, was included as well. SR140333
      had no significant effect on either the EAR or the LAR compared with saline
      control inhalations. However, the NK1 receptor antagonist significantly reduced
      the OA-induced AHR to histamine, both after the EAR at 5 h after OA challenge
      (1.77 +/- 0.13-fold increase in histamine reactivity versus 2.50 +/- 0.25-fold
      increase in the control animals, p < 0.01) and after the LAR at 23 h after OA
      challenge (1.15 +/- 0.12-fold increase versus 1.98 +/- 0. 34-fold increase,
      respectively, p < 0.05). Moreover, bronchoalveolar lavage studies performed at 25
      h after the second OA provocation indicated that SR140333 significantly inhibited
      the allergen-induced infiltration of eosinophils, neutrophils, and lymphocytes in
      the airways (p < 0.05 for all observations), whereas a tendency to reduced
      accumulation of ciliated epithelial cells in the airway lumen was observed (p =
      0.10). These results indicate that the NK1 receptor is involved in the
      development of allergen-induced AHR to histamine, and that NK1 receptor-mediated
      infiltration of inflammatory cells in the airways may contribute to this AHR.

PMID- 9927354
TI  - Airway neural responses to kinins: tachyphylaxis and role of receptor subtypes.
AB  - To further define the role of neural responses in the hyperreactivity of inflamed
      human upper airways to bradykinin (BK), we determined if repeated challenges with
      BK led to tachyphylaxis of neurally mediated responses in subjects with perennial
      allergic rhinitis. We also tested the hypothesis that enhanced reactivity to
      kinins in inflamed airways was caused by induction of B1-kinin receptors by
      comparing the effects of the selective B1-receptor agonist, des-Arg10
      lysylbradykinin, and the B2 receptor agonist, BK, in the lower airways of
      asthmatics and in the upper airways of subjects with perennial allergic rhinitis.
      Repeated BK challenges led to tachyphylaxis of sneezing and of neurally mediated
      serous glandular secretion in subjects with perennial allergic rhinitis.
      Surprisingly, tachyphylaxis of increased local vascular permeability was also
      observed. By contrast, repeated challenges with BK in normal subjects led to
      reproducible increases in vascular permeability. Provocation with des-Arg10
      lysylbradykinin did not cause bronchoconstriction in asthmatic subjects or
      increase glandular secretion or vascular permeability in the upper airways of
      subjects with rhinitis. We conclude that increased reactivity to kinins in
      inflamed human airways is mediated, at least in part, by neural reflexes, and is
      not caused by induction of B1-receptors.

PMID- 9927355
TI  - Large scale implementation of a respiratory therapist-driven protocol for
      ventilator weaning.
AB  - We prospectively investigated the large-scale implementation of a respiratory
      therapist-driven protocol (TDP) that included 117 respiratory care practitioners
      (RCPs) managing 1,067 patients with respiratory failure over 9,048 patient days
      of mechanical ventilation. During a 12-mo period, we reintroduced a previously
      validated protocol that included a daily screen (DS) coupled with spontaneous
      breathing trials (SBTs) and physician prompt, as a TDP without daily input from a
      physician or "weaning team." With graded, staged educational interventions at 2
      mo intervals, RCPs had a 97% completion rate and a 95% correct interpretation
      rate for the DS. The frequency with which patients who passed the DS underwent
      SBTs increased throughout the implementation process (p < 0.001). As the year
      progressed, RCPs more often considered SBTs once patients had passed a DS (p <
      0.001), and physicians ordered more SBTs (46 versus 65%, p = 0.004). Overall,
      SBTs were ordered more often on the medicine than on the surgical services (81
      versus 63%, p = 0.001), likely reflecting medical intensivists' prior use of this
      protocol. Important barriers to protocol compliance were identified through a
      questionnaire (89 respondents, 76%), and included: Physician unfamiliarity with
      the protocol, RCP inconsistency in seeking an order for an SBT from the
      physician, specific reasons cited by the physician for not advancing the patient
      to a SBT, and lack of stationary unit assignments by RCPs performing the
      protocol. We conclude that implementation of a validated weaning strategy is
      feasible as a TDP without daily supervision from a weaning physician or team.
      RCPs can appropriately perform and interpret DS data more than 95% of the time,
      but significant barriers to SBTs exist. Through a staged implementation process,
      using periodic reinforcement of all participants in ventilator management,
      improved compliance with this large-scale weaning protocol can be achieved.

PMID- 9927356
TI  - Accuracy of pulse oximetry in sickle cell disease.
AB  - Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and
      may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of
      particular importance in SCD. To assess the accuracy of pulse oximetry in the
      diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of
      arterial oxygen saturation (SpO2) in adult patients with SCD and acute
      vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 =
      oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co
      oximetry. We accepted SpO2 readings only if they were stable and characterized by
      strong and regular photoplethysmographic waves on the oximeter screen. To assess
      the position of these patients' oxyhemoglobin dissociation curves, we plotted
      arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We
      found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s
      ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin
      percentage (by an average of 3.4 percentage points), but it almost always
      accurately estimated SaO2 (underestimating on average by 1.1 percentage points).
      The error in SpO2 was never enough to classify a hypoxemic patient erroneously as
      normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as
      strong and regular photoplethysmographic waves are present, pulse oximeters can
      be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.

PMID- 9927357
TI  - Inhibition of beta-adrenergic desensitization by KCa channels in human
      trachealis.
AB  - We examined the reduced responsiveness to beta-adrenergic receptor agonists (beta
      agonists) after exposure to beta-agonists, and the mechanisms underlying this
      phenomenon in isolated human tracheal smooth muscle, using isometric tension
      records to test the hypothesis that repeated inhalation of beta-agonists leads to
      reduced responsiveness to beta-agonists. The inhibitory effects of isoproterenol
      (ISO) on contraction by spasmogens participating in asthma attacks diminished
      markedly after continuous exposure to ISO (0.0003 to 3 microM) for 45 min;
      moreover, when ISO was repeatedly applied for 10 min to tissues precontracted by
      methacholine every 30 min, the relaxant effects of ISO gradually attenuated after
      these repeated applications. In contrast, reduced beta-adrenergic relaxation
      after continuous and repeated exposure to agonists did not occur when tissues
      were preincubated with 2 microg/ ml cholera toxin (CTX), which irreversibly
      activates guanosine triphosphate (GTP)-binding protein (Gs) coupled with beta
      adrenergic receptors, for 6 h. However, the CTX inhibition disappeared in the
      presence of iberiotoxin, a selective inhibitor of large conductance Ca2+
      activated K+ (KCa) channels. Our results demonstrate that continuous and repeated
      exposure to beta-agonists leads to beta-adrenergic desensitization, and that
      activation of KCa channels by Gs prevents this desensitization.

PMID- 9927358
TI  - Randomized placebo-controlled crossover trial of continuous positive airway
      pressure for mild sleep Apnea/Hypopnea syndrome.
AB  - The minimal disease severity at which patients with the sleep apnea/hypopnea
      syndrome (SAHS) gain benefit from treatment is not well characterized, although a
      pilot study of continuous positive airway pressure (CPAP) therapy showed daytime
      improvements in patients with 5 to 15 apneas + hypopneas per hour slept (AHI). We
      have thus performed a second, larger, randomized, placebo- controlled study in a
      prospective series of 34 patients (13 female) with mild SAHS (AHI 5 to 15) and
      daytime sleepiness. Patients spent 4 wk on CPAP treatment and 4 wk on an oral
      placebo, with randomization of treatment order, and daytime assessments on the
      last day of each treatment. Effective CPAP use averaged 2.8 +/- 2.1 h (mean +/-
      SD) per night. Compared with placebo, CPAP improved symptom score (p < 0.01),
      subjective (Epworth; p < 0.01) but not objective (maintenance of wakefulness
      test; p > 0.2) sleepiness, performances on 2 of 7 cognitive tasks (p < 0.02),
      depression score (p < 0.01), and five subscales of the SF-36 health/functional
      status questionnaire (p </= 0.03). Fourteen of 34 patients preferred CPAP. In 14
      patients with AHI in the range 5 to 10, symptoms, cognitive function,
      psychological well-being and quality of life were improved. These results confirm
      benefits for daytime function after CPAP treatment for mild SAHS, but highlight
      unacceptability of CPAP in many such patients.

PMID- 9927359
TI  - Risk factors for rifampin-monoresistant tuberculosis: A case-control study.
AB  - Rifampin is the cornerstone of short-course chemotherapy for the treatment of
      tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance
      to isoniazid alone or in combination with other antituberculous medications. We
      conducted a retrospective case-control study to identify risk factors for RMR-TB.
      Complete records for 21 of a total of 26 RMR patients from 1990 to 1997 were
      available for review, and were compared with those of 48 patients with drug
      susceptible TB, controlling for year of diagnosis. Cases more frequently had a
      history of TB than did controls (61% versus 22%, p < 0.01), and were more often
      human immunodeficiency virus (HIV) positive (81% versus 46%, p = 0.02). With
      control for HIV status, cases were more likely to have extrapulmonary involvement
      (47.6% versus 11.6%, p = 0.05). Four cases (19%) and one control (2. 1%) died (p
      = 0.02) during hospitalization. Cases more often had a history of incarceration
      (71.4% versus 37.5%, p = 0.09). Among the 13 cases with a history of TB, five had
      evidence of malabsorption (vomiting and/or diarrhea), versus none of the 11
      controls with prior TB. These data support the hypothesis that RMR is seen
      primarily in individuals with a history of TB and who are HIV positive. Cases
      were frequently noncompliant with previous treatment for TB, had a history of
      incarceration, and had poor outcomes.

PMID- 9927360
TI  - Epithelial permeability, inflammation, and oxidant stress in the air spaces of
      smokers.
AB  - The mechanism responsible for the increased air-space permeability in cigarette
      smokers is unknown. The aim of this study was to assess the acute and chronic
      effects of cigarette smoking on epithelial permeability, inflammation, and
      oxidant stress in the air spaces of smokers. Fourteen cigarette smokers underwent
      99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) lung scans after
      abstaining from smoking for 12 h (chronic smoking) and 1 h after smoking two
      cigarettes (acute smoking). Each smoker also underwent bronchoscopy and
      bronchoalveolar lavage (BAL) after either chronic (n = 8) or acute smoking (n =
      7). Seven nonsmokers also underwent bronchoscopy and BAL. The time to 50%
      clearance of 99mTc-DTPA (t50) after chronic smoking was 16.7 +/- 1. 3 min (mean
      +/- SE), and was further reduced after acute smoking to 14.8 +/- 1.0 min (p <
      0.01). Neutrophil numbers were increased in bronchoalveolar lavage fluid (BALF)
      in the acute smoking group as compared with the nonsmokers (p < 0.05). Superoxide
      release from mixed BAL leukocytes was increased after chronic (p < 0.01) and
      acute (p < 0.001) smoking, as were thiobarbituric acid-reactive species (TBARS),
      providing evidence of lipid peroxidation in plasma (chronic, p < 0.05; acute, p <
      0.05). Trolox equivalent antioxidant capacity (TEAC) was reduced in plasma (p <
      0.001) and increased in BALF (p < 0.05) in both smoking groups. The study
      therefore showed an acute increase in epithelial permeability and an increase in
      the number of neutrophils in the air spaces of cigarette smokers concomitant with
      evidence of increased oxidant stress.

PMID- 9927361
TI  - Assessment of airway function using partial expiratory flow-volume curves: How
      reliable are measurements of maximal expiratory flow at frc during early infancy?
AB  - We investigated the extent to which measurements of maximal expiratory flow at
      FRC (V EmaxFRC) are influenced by the dynamic increase of FRC in young infants by
      superimposing partial forced expiratory flow-volume curves on those obtained
      after lung inflation to 2 kPa (20 cm H2O) in 12 infants during the first month of
      life. The elastic equilibrium volume (EEV) of the respiratory system was
      estimated by extrapolating the passive expiratory time constant (obtained after
      lung inflation but prior to forced deflation) to zero flow. There was a very
      strong relationship between V EmaxFRC (which ranged from 11 to 190 ml/s) and the
      extent to which FRC was dynamically increased above EEV (range: 0 to 5 ml/kg), r2
      = 0.88. The results of this study suggest that, although V EmaxFRC remains a
      useful means of measuring peripheral airway function in infants, its values
      should be interpreted with caution during the neonatal period. In particular, the
      relatively high V EmaxFRC values reported in healthy newborn infants may reflect
      differences in breathing strategy rather than airway structure. More meaningful
      within- and between-infant comparisons of peripheral airway function may be
      obtained by calculating forced expiratory flows at a fixed interval (e.g., 3
      ml/kg) above EEV, rather than at the FRC that is operational at the time of
      measurement.

PMID- 9927362
TI  - Balance between proinflammatory cytokines and their inhibitors in bronchial
      lavage from patients with status asthmaticus.
AB  - Status asthmaticus (SA) is an acute respiratory failure combining an acute
      bronchospastic reaction with a severe airway inflammation. We previously reported
      an important influx of neutrophils and an increased secretion of interleukin-8
      (IL-8) in patients with SA. The aim of this prospective study was to evaluate in
      bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation
      (MV) the concentrations of cytokines and related mediators which have the ability
      to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta],
      IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators
      (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor
      antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine
      the relative importance of both pro- and anti-inflammatory mediators, the net
      inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase
      intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549
      epithelial cell line. These data were compared with those obtained from patients
      who required MV without respiratory disease (V, n = 4), controlled asthma (A, n =
      11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF
      alpha, and of the active form of TGF-beta1 were significantly higher in SA
      compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent
      form of TGF-beta1, and of the sTNFRI and II were not significantly different
      between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra
      and IL-1beta was significantly higher in patients with SA compared with the other
      groups, whereas there was no difference for the ratio between both types of sTNFR
      and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL
      from patients with SA, the net inflammatory activity was found to be
      proinflammatory and mainly due to the presence of bioactive IL-1beta (79%
      inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser
      extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies).

PMID- 9927363
TI  - Evidence of the effectiveness of continuous positive airway pressure in the
      treatment of sleep apnea/hypopnea syndrome.
AB  - Continuous positive airway pressure (CPAP) is worldwide considered as the
      standard treatment of sleep apnea/hypopnea syndrome (SAHS) although studies on
      the effectiveness of this treatment are limited. The aim of our study was to
      evaluate the effectiveness of CPAP in improving SAHS-related symptoms, daytime
      function, perceived health status, and quality of life in patients with moderate
      to severe SAHS. The effect of conservative treatment (CT) measures-sleep hygiene
      and weight loss- was compared with CT + CPAP. We included 105 consecutive
      patients (13 females, age 53 +/- 10 yr, body mass index [BMI] = 32 +/- 6 kg/m2,
      apnea/hypopnea index [AHI] = 56 +/- 20, Epworth sleepiness scale [ESS] = 12 +/-
      5) who met our criteria for CPAP treatment. Patients were randomly allocated in
      two groups of similar characteristics. Group 1 (n = 37) was asked to improve
      sleep hygiene and started a weight loss program. Group 2 (n = 68) received, in
      addition, treatment with CPAP. Both groups were followed through weekly telephone
      calls and appointments. Sleepiness, other symptoms related to SAHS, daytime
      function, perceived health status, and quality of life were assessed through
      questionnaires at inclusion and after 3 mo of treatment. The relief of sleepiness
      and other SAHS-related clinical symptoms and improvement in perceived health
      status was much greater in Group 2 receiving CT + CPAP compared with Group 1,
      only receiving CT. The odds of experiencing a treatment response with CPAP + CT
      compared with CT alone was 6.52 (odds ratio [OR] = 2.51 to 17.6, 95% confidence
      interval [95% CI]). CPAP is currently the treatment of choice. At this time, the
      indication of CPAP treatment in moderate to severe SAHS is adequately supported.

PMID- 9927364
TI  - Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health
      Study.
AB  - Obstructive sleep apnea syndrome is a well recognized cause of excessive
      sleepiness; however, the relation of sleepiness to mild sleep-disordered
      breathing (SDB), which affects as much as half the adult population, is
      uncertain. In order to explore this relation, we conducted a cross-sectional
      cohort study of community-dwelling adults participating in the Sleep Heart Health
      Study, a longitudinal study of the cardiovascular consequences of SDB. The study
      sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr.
      Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep
      disordered breathing was quantified by the respiratory disturbance index (RDI),
      defined as the number of apneas plus hypopneas per hour of sleep, measured during
      in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to <
      15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score
      was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5
      to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant
      modification of this effect by age, sex, body mass index, or evidence of chronic
      restriction of sleep time or periodic limb movement disorder. The percentage of
      subjects with excessive sleepiness, defined as an ESS score >/= 11, increased
      from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001).
      We conclude that SDB is associated with excess sleepiness in community-dwelling,
      middle-aged and older adults, not limited to those with clinically apparent sleep
      apnea.

PMID- 9927365
TI  - Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine.
      Recently, pentoxifylline (POF) has been shown to suppress the synthesis of TNF
      alpha from lipopolysaccharide (LPS)-stimulated human monocytes in cell cultures
      and in vivo. The aim of this study was to investigate whether POF-induced
      suppression of TNF-alpha secretion affects peripheral blood monocytes (PBM) and
      alveolar macrophages (AM) equally, and whether POF is able to suppress the
      spontaneous TNF-alpha production from AM in pulmonary sarcoidosis in vitro. In
      seven patients without interstitial lung disease we studied the effect of POF on
      LPS-stimulated PBM and AM cultured for 24 h. In six patients with sarcoidosis we
      investigated the effect of POF on the enhanced spontaneous TNF-alpha production
      by AM in vitro. POF induced a dose-dependent suppression of the LPS-stimulated
      TNF-alpha production which was not different for PBM and AM, respectively. In
      sarcoidosis, POF inhibited the spontaneous TNF-alpha production of AM at 0.1 mM
      by 91% and at 1 mM by 98%. In conclusion, POF inhibits LPS-induced TNF-alpha
      production from PBM and AM to a similar extent and can also inhibit the
      exaggerated spontaneous TNF-alpha production from AM in sarcoidosis in vitro.
      This may be the basis for further clinical trials to evaluate POF as an
      immunotherapeutic agent in sarcoidosis.

PMID- 9927366
TI  - Effect of spontaneous breathing trial duration on outcome of attempts to
      discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group.
AB  - The duration of spontaneous breathing trials before extubation has been set at 2
      h in research studies, but the optimal duration is not known. We conducted a
      prospective, multicenter study involving 526 ventilator-supported patients
      considered ready for weaning, to compare clinical outcomes for trials of
      spontaneous breathing with target durations of 30 and 120 min. Of the 270 and 256
      patients in the 30- and 120-min trial groups, respectively, 237 (87.8%) and 216
      (84.8%), respectively, completed the trial without distress and were extubated (p
      = 0.32); 32 (13.5%) and 29 (13.4%), respectively, of these patients required
      reintubation within 48 h. The percentage of patients who remained extubated for
      48 h after a spontaneous breathing trial did not differ in the 30- and 120-min
      trial groups (75.9% versus 73.0%, respectively, p = 0.43). The 30- and 120-min
      trial groups had similar within-unit mortality rates (13 and 9%, respectively)
      and in-hospital mortality rates (19 and 18%, respectively). Reintubation was
      required in 61 (13.5%) patients, and these patients had a higher mortality (20 of
      61, 32.8%) than did patients who tolerated extubation (18 of 392, 4.6%) (p <
      0.001). Neither measurements of respiratory frequency, heart rate, systolic blood
      pressure, and oxygen saturation during the trial, nor other functional
      measurements before the trial discriminated between patients who required
      reintubation from those who tolerated extubation. In conclusion, after a first
      trial of spontaneous breathing, successful extubation was achieved equally
      effectively with trials targeted to last 30 and 120 min.

PMID- 9927367
TI  - Interstitial lung disease: A quantitative study using the adaptive multiple
      feature method.
AB  - We have previously described an adaptive multiple feature method (AMFM) for the
      objective assessment of global and regional changes in pulmonary parenchyma to
      detect emphysema. This computerized method uses a combination of statistical and
      fractal texture features for characterization of lung tissues based upon high
      resolution computed tomography (HRCT) scans. This present study was a substantial
      extension of the AMFM to simultaneously discriminate between multiple pulmonary
      disease processes. Normal subjects and those with emphysema, idiopathic pulmonary
      fibrosis (IPF), or sarcoidosis were studied. The AMFM was compared with two
      currently utilized computer-based methods: mean lung density (MLD) and the
      histogram analysis (HIST). Globally, when comparing two-subject groups the AMFM
      overall accuracy was 2 to 18% better than the overall accuracy of MLD and as much
      as 36% better than the accuracy of the HIST methods. In three-subject group
      discrimination tasks, the AMFM performed 7 to 27% better than the MLD and 4 to
      36% better than the HIST methods. Finally, in discriminating all four subject
      groups at a time, the AMFM overall accuracy was 81%, which was 21% better than
      the MLD and 25% better than the HIST method. In most three-subject group
      comparisons and in the four-subject group comparison, the AMFM was significantly
      (p < 0.01) better than the MLD and HIST methods. Next, the AMFM was applied to
      local discrimination between normal and each disease group individually. The
      normal versus emphysema, normal versus IPF, and normal versus sarcoidosis samples
      were discriminated with an accuracy of 95, 86, and 77%, respectively. The AMFM is
      an objective quantitative method that can be adapted for successful
      discrimination of multiple parenchymal lung diseases.

PMID- 9927368
TI  - Association of HLA class I antigens with diffuse panbronchiolitis in Korean
      patients.
AB  - Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease of
      unknown etiology. Observations of significantly increased frequency of human
      leukocyte antigen (HLA)-B54 in Japanese patients and occurrence of familial cases
      suggest possible genetic predisposition to the disease susceptibility. To
      evaluate the possible association of HLA with the disease in Koreans, we have
      analyzed 30 patients for HLA class I (A, B, C) and class II (DR) antigens by the
      serologic and DNA typing methods, respectively. The most significant change in
      the patients compared to the control subjects was increased frequency of HLA-A11
      (53.3% versus 17.5%, corrected p [pc] = 1.2 x 10(-)4, odds ratio [OR] = 5.4). In
      addition, B55 showed significant positive association (16.7% versus 3.5%, pc =
      0.05, OR = 5.5), and B62 and Cw4 showed rather weak association with the disease.
      Certain A11-associated haplotypes showed much stronger positive association with
      the disease, compared to A11 antigen itself. Observations of a strong association
      of HLA-A11 in Koreans and B54 in Japanese with DPB suggest that the candidate
      gene(s) responsible for the disease susceptibility is located within the HLA
      class I region, most probably between HLA-A and HLA-B loci.

PMID- 9927369
TI  - Both intravenous and inhaled lidocaine attenuate reflex bronchoconstriction but
      at different plasma concentrations.
AB  - Intravenous lidocaine can attenuate bronchial hyperreactivity. However, lidocaine
      inhalation might yield the same or better results at higher airway and lower
      lidocaine plasma concentrations. Therefore, we tested in awake volunteers with
      bronchial hyperreactivity the effect of lidocaine on histamine-induced
      bronchoconstriction administered either intravenously or as an aerosol. After
      approval of the local ethics committee, 15 volunteers were enrolled in this
      placebo-controlled, double-blinded, randomized study. Volunteers were selected by
      showing a decrease in FEV1 greater than 20% of baseline (PC20) in response to
      histamine inhalation. On three different days the challenge was repeated after
      pretreatment with either intravenous lidocaine, inhaled lidocaine, or placebo.
      Blood samples for determination of lidocaine plasma concentration were drawn.
      Comparisons were made using the Friedman and Wilcoxon signed-rank tests. Baseline
      PC20 was 6.4 +/- 1.1 mg. ml-1. Both inhalation of lidocaine and intravenous
      administration significantly increased PC20 to 14.8 +/- 3.5 mg. ml-1 and 14.2 +/-
      2. 5 mg. ml-1, respectively (p = 0.0007). Peak plasma lidocaine concentrations at
      the end of challenges were 0.7 +/- 0.1 microg. ml-1 (inhaled) and 2.2 +/- 0.1
      microg. ml-1 (i.v.). However, 7 of 15 subjects showed an initial decrease of FEV1
      greater than 5% following lidocaine inhalation. While both intravenous as well as
      inhaled lidocaine attenuate reflex bronchoconstriction significantly, lidocaine
      plasma concentrations are significantly lower after inhalation. However, the high
      incidence of initial bronchoconstriction to lidocaine inhalation may limit its
      use in patients with asthma and thus offers therapeutic advantages for
      intravenous lidocaine.

PMID- 9927370
TI  - Persistent airway inflammation but accommodated antioxidant and lung function
      responses after repeated daily exposure to nitrogen dioxide.
AB  - Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may
      induce deterioration of respiratory health. In this study the effects of repeated
      daily exposure to NO2 on airway antioxidant status, inflammatory cell and
      mediator responses, and lung function were examined. Healthy nonsmoking subjects
      were exposed under controlled conditions to air (once) and to 2 ppm of NO2 for 4
      h on four consecutive days. Lung function measurements were made before and
      immediately after the end of each exposure. Bronchoscopy with endobronchial
      biopsies, bronchial wash (BW), and bronchoalveolar lavage (BAL) was carried out
      1.5 h after the air exposure and after the last exposure to NO2. Repeated NO2
      exposure resulted in a decrease in neutrophil numbers in the bronchial
      epithelium. The BW revealed a twofold increase in content of neutrophils (p <
      0.05) and a 1.5-fold increase in myeloperoxidase (MPO) (p < 0.01) indicative of
      both migration and activation of neutrophils in the airways. After the fourth NO2
      exposure, antioxidant status of the airway fluid was unchanged. Significant
      decrements in FEV1 and FVC were found after the first exposure to NO2, but these
      attenuated with repeated exposures. Together, these data indicate that four
      sequential exposures to NO2 result in a persistent neutrophilic inflammation in
      the airways, whereas changes in pulmonary function and airway antioxidants are
      resolved. We conclude that NO2 is a proinflammatory air pollutant under
      conditions of repeated exposure.

PMID- 9927371
TI  - Vascular endothelium viability and function after total cardiopulmonary bypass in
      neonatal piglets.
AB  - Endothelium dysfunction with severe pulmonary hypertension may occur after total
      cardiopulmonary bypass (CPB) in infants as a result of a widespread inflammatory
      response. The aim of this study was to separate out the effects of lung ischemia
      reperfusion from membrane oxygenator-induced activation of leukocytes on the
      function and viability of the pulmonary and systemic endothelia in neonatal
      piglets submitted to 90-min total CPB followed by 60-min reperfusion or in sham
      animals. Hemodynamics, gas exchange, endothelial-dependent relaxation in
      pulmonary and femoral arteries, and lung and skeletal muscle myeloperoxidase
      activity were assessed before, during, and after CPB, i.e., after reperfusion.
      Pulmonary and aortic endothelial cells and circulating leukocytes were harvested
      to assess reperfusion-induced changes in endothelial cells' viability and
      proliferation, and leukocyte-endothelial cell adhesion and cytotoxicity. Gas
      exchange worsened after reperfusion with pulmonary hypertension, increase in lung
      but not skeletal myeloperoxidase, and reduction of endothelial-dependent
      relaxation in pulmonary but not femoral arteries. After reperfusion, viabilities
      of pulmonary and aortic endothelial cells were reduced to 50%, endothelial cell
      growths were faster in pulmonary arteries than aorta, and leukocyte-pulmonary
      endothelial cell adhesion and cytotoxicity increased. These results suggest that
      in total CPB lung ischemia-reperfusion aggravates the inflammatory response and
      predisposes the lung endothelium to leukocyte-mediated injury.

PMID- 9927372
TI  - Development of pulmonary hypertension after lung volume reduction surgery.
AB  - This prospective, longitudinal study was designed to assess the hemodynamic
      changes occurring in patients who undergo lung volume reduction surgery (LVRS).
      Patients with emphysema treated with LVRS underwent hemodynamic evaluation before
      and after surgery. The study group consisted of nine patients with an average age
      of 64.4 yr. FEV1 rose significantly from 0.64 preoperatively to 0.99 L
      postoperatively. After surgery, pulmonary artery (PA) systolic pressure rose to
      47.9 +/- 12.4 mm Hg, meeting criteria for development of pulmonary hypertension.
      In six patients, the elevation in PA pressure was attributed to an increase in
      the pulmonary vascular resistance, but for all nine patients the change was not
      statistically significant. The pulmonary artery occulsion pressure (PAOP) did not
      change postoperatively. There was no correlation of PAOP with global left
      ventricular ejection fraction. While preoperatively there was a negative
      correlation between symptoms (Mahler dyspnea index) and PA pressure, after
      surgery the change in PA pressures did not correlate with the change in symptoms
      (Mahler transitional dyspnea index). We concluded that development of pulmonary
      hypertension may occur after LVRS in patients whose symptomatic status improves
      and in whom this condition was not present preoperatively.

PMID- 9927373
TI  - Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of
      tachykinins, bradykinin, and nitric oxide.
AB  - Gastroesophageal acid reflux into the airways can trigger asthma attacks. Indeed,
      citric acid inhalation causes bronchoconstriction in guinea pigs, but the
      mechanism of this effect has not been fully clarified. We investigated the role
      of tachykinins, bradykinin, and nitric oxide (NO) on the citric acid- induced
      bronchoconstriction in anesthetized and artificially ventilated guinea pigs.
      Citric acid inhalation (2-20 breaths) caused a dose-dependent increase in total
      pulmonary resistance (RL). RL value obtained after 10 breaths of citric acid
      inhalation was not significantly different from the value obtained after 20
      breaths (p = 0.22). The effect produced by a half-submaximum dose of citric acid
      (5 breaths) was halved by the bradykinin B2 receptor antagonist HOE 140 (0.1
      micromol x kg-1, intravenous) and abolished by the tachykinin NK2 receptor
      antagonist SR 48968 (0.3 micromol x kg-1, intravenous). Bronchoconstriction
      induced by a submaximum dose of citric acid (10 breaths) was partially reduced by
      the administration of HOE 140, SR 48968, or the NK1 receptor antagonist CP-99,994
      (8 micromol x kg-1, intravenous) alone and completely abolished by the
      combination of SR 48968 and CP-99,994. Pretreatment with the NO synthase
      inhibitor, L-NMMA (1 mM, 10 breaths every 5 min for 30 min) increased in an L
      arginine-dependent manner the effect of citric acid inhalation on RL. HOE 140 and
      CP-99,994 markedly reduced the L-NMMA-potentiated bronchoconstriction to inhaled
      citric acid. We conclude that citric acid-induced bronchoconstriction is caused
      by tachykinin release from sensory nerves, which, in part, is mediated by
      endogenously released bradykinin. Simultaneous release of NO by citric acid
      inhalation counteracts tachykinin-mediated bronchoconstriction. Our study
      suggests a possible implication of these mechanisms in asthma associated with
      gastroesophageal acid reflux and a potential therapeutic role of tachykinin and
      bradykinin antagonists.

PMID- 9927374
TI  - Response to inhaled nitric oxide in acute lung injury depends on distribution of
      pulmonary blood flow prior to its administration.
AB  - Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced
      by improvements in oxygenation, are variable. We hypothesized that the effect of
      iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In
      the present study we evaluated the effect of iNO on PBF in normal healthy dogs
      and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n =
      5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA"
      (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose
      endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before
      giving the same dose of OA. Measurements of regional PBF and lung water
      concentration (LWC) using positron emission tomography (PET) and H215O were
      performed before and after OA or placebo, and then again at concentrations of 10,
      40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell
      significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these
      animals, PBF redistributed from the dorsal edematous regions of the lungs to the
      nondependent zones, thus partially preserving normal ventilation/ perfusion
      relationships. As in the normal animals, in Group OA only, iNO did not
      significantly change either PBF or oxygenation. In Group E+OA, the administration
      of low-dose endotoxin eliminated perfusion redistribution from the dorsal
      edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53
      mm Hg, a decrease that was significantly greater than that in Group OA only. In
      Group E+OA, administration of iNO restored perfusion redistribution to a similar
      level as in Group OA only, which was associated with a significant improvement in
      PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40
      ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on
      the pre-iNO perfusion pattern, which may help explain the variable response to
      iNO often observed in patients with acute respiratory distress syndrome.

PMID- 9927375
TI  - Response to inhaled nitric oxide in patients with acute right heart syndrome.
AB  - Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown to
      decrease pulmonary artery pressures but not increase cardiac output in
      hemodynamically stable patients with a variety of causes of pulmonary
      hypertension. The response to iNO in hemodynamically unstable patients with acute
      right heart syndrome has not been previously described. We determined the
      response to iNO in 26 critically ill adult patients with acute right heart
      failure defined by echocardiographic criteria. Patients received iNO through the
      inspiratory limb of the ventilator in increments of 10 ppm with hemodynamic and
      gas-exchange measurements made before and after each level. When maximal effect
      was seen, iNO was discontinued to compare parameters with baseline. iNO
      significantly increased cardiac output (5.5 +/- 3 to 6.4 +/- 4 L/min), stroke
      volume (54 +/- 27 to 65 +/- 38 ml), and mixed-venous oxygen saturation (69 +/- 8
      to 73 +/- 10%), all p < 0.01. With discontinuation of iNO, all parameters
      returned immediately to baseline. These parameters of improved perfusion were
      related to a decrease in pulmonary vascular pressures and resistance. In a subset
      of approximately 50% of patients, these changes were substantial (> 20%) and in
      approximately 25% of all patients, the improvement in hemodynamic measures
      permitted a decrease in other vasoactive drug administration. The mean
      concentration of iNO required to achieve these effects was 35 ppm, and 85% of
      patients exhibiting a substantial improvement in hemodynamics did so at a
      concentration of iNO of less than or equal to 40 ppm. Underlying causes of right
      heart failure and baseline hemodynamics did not predict response to iNO, but the
      use of alpha-agonist catecholamines did. We conclude iNO improves hemodynamics in
      patients with respiratory failure, shock, and right ventricular dysfunction.
      Although mortality was not a key end point in this pilot study, it was high for
      both responders and nonresponders to this therapy. Further evaluation of the role
      of iNO in this patient population is supported by these data.

PMID- 9927376
TI  - TRFK-5 reverses established airway eosinophilia but not established
      hyperresponsiveness in a murine model of chronic asthma.
AB  - We studied the effects of an anti-interleukin (IL)-5 monoclonal antibody (TRFK-5)
      or dexamethasone (DEX) to reverse already established airway hyperresponsiveness
      (AHR) and tissue eosinophilia in a Schistosoma mansoni antigen-sensitized and
      airway-challenged mouse model of chronic asthma. In this model at 4 d after
      antigen challenge there is dramatic bronchoalveolar lavage fluid (BAL)
      eosinophilia, AHR to intravenous methacholine (MCh), and histologic evidence of
      peribronchial eosinophilic infiltration and mucoid cell hyperplasia. These
      changes persist for up to 2 wk after antigen challenge. Treatment with DEX from
      Days 4 through 10 significantly reduced established airway eosinophilia compared
      with animals sham-treated with saline from Days 4 -10 (120 +/- 29
      eosinophils/microl BAL for DEX-treated mice versus 382 +/- 60 eosinophils/microl
      BAL for sham-treated animals, p < 0.01). DEX-treated mice also had dramatically
      reduced mucoid cell hyperplasia, and airway responsiveness returned to normal. In
      contrast, TRFK-5 given during the same time period reduced airway eosinophilia
      (86 +/- 32 eosinophils/microl BAL versus 382 +/- 60 eosinophils/microl BAL, p <
      0.01) but did not reduce goblet cell hyperplasia or reverse already established
      AHR. Treatment with DEX but not TRFK-5 also inhibited interferon gamma (IFN
      gamma) content of BAL fluid (0.49 +/- 0.09 ng/ml BAL fluid for DEX versus 1.50 +/
      0.24 ng/ml BAL fluid and 1.36 +/- 0.13 ng/ml BAL fluid for TRFK-5 and sham
      treated mice, respectively, both p < 0.001 versus DEX). Thus, treatment with DEX
      reduces established eosinophilic airway inflammation and AHR in S. mansoni
      sensitized and airway-challenged mice but treatment with TRFK-5 reversed
      established eosinophilia without ameliorating established AHR. Together, these
      data suggest that once airway inflammation develops, neutralizing the effects of
      IL-5 or reducing eosinophilia alone may not result in inhibiting established AHR
      in atopic asthma.

PMID- 9927377
TI  - Comparison between nasal and bronchial inflammation in asthmatic and control
      subjects.
AB  - Although asthma and rhinitis often coexist, it is still unknown whether they are
      characterized by a similar inflammatory profile. We studied eosinophilic
      infiltration, epithelial shedding and reticular basement membrane thickness in
      nasal and bronchial biopsies of six control subjects, 15 untreated allergic
      asthmatics with perennial rhinitis, and six corticosteroid-dependent (CSD)
      asthmatics. In nasal and bronchial biopsies, eosinophils were greater in
      untreated asthmatics than in control subjects and CSD asthmatics (p = 0.001). In
      untreated asthmatics, eosinophils were higher in bronchial than in nasal biopsies
      (p = 0.002). In nasal and bronchial biopsies, reticular basement membrane
      thickness was greater in untreated and CSD asthmatics than in control subjects
      (nasal: p < 0.008 and p < 0. 004; bronchial: p < 0.001 and p < 0.008). In
      untreated and CSD asthmatics, reticular basement membrane thickness was greater
      in bronchial than in nasal biopsies (p = 0.001; Wilcoxon's W test). Nasal
      epithelium was not shed in all the study groups. In untreated asthmatics,
      bronchial epithelium shedding was greater than in control subjects or CSD
      asthmatics (p < 0.005), and it was greater than nasal epithelium shedding (p <
      0.006). This study has shown that, although concomitant, the extent of
      eosinophilic inflammation of reticular basement membrane thickness and of the
      epithelium shedding is greater in bronchial than in nasal mucosa of asthmatic
      patients with perennial rhinitis.

PMID- 9927378
TI  - Serum matrix metalloproteinase-9:Tissue inhibitor of metalloproteinase-1 ratio
      correlates with steroid responsiveness in moderate to severe asthma.
AB  - Asthma presents a variable clinical response to corticosteroids (CS). Because CS
      more likely act on inflammation than on tissue remodeling, the presence of
      bronchial structural changes in certain asthmatics may explain their limited
      clinical response to CS. Matrix metalloproteinase-9 (MMP-9) and its inhibitor,
      tissue inhibitor of metalloproteinase-1 (TIMP-1), are, respectively, involved in
      tissue inflammatory processes and fibrogenic processes. Previous reports have
      suggested that MMP-9:TIMP-1 ratio may reflect the balance between these two
      processes in various diseases. This study evaluated the relation of this ratio
      and the response to CS in severe asthma. Twenty asthmatics with low baseline FEV1
      (59 +/- 4% predicted) and >/= 30 % increase with beta2-agonist were recruited.
      Serum MMP-9 and TIMP-1 levels were measured and correlated with response to an
      oral CS trial (methylprenisolone 40 mg/d for 14 d). With oral CS, FEV1 changes
      (DeltaFEV1) ranged from -15 to +43%. The DeltaFEV1 closely correlated with the
      MMP-9:TIMP-1 ratios (rho = 0. 79, p = 0.0006). In conclusion, serum MMP-9: TIMP-1
      ratio could predict the response of oral CS therapy in asthma. The low MMP-9:TIMP
      1 ratio observed in subjects with little or no FEV1 improvement with CS supports
      the hypothesis that, in these asthmatic subjects, bronchial fibrogenesis
      predominates over inflammation.

PMID- 9927379
TI  - Ventilator-associated lung injury decreases lung ability to clear edema in rats.
AB  - Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT)
      excursions producing microvascular leakage and pulmonary edema. However, the
      effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K
      ATPase function have not been elucidated. We studied lung edema clearance in the
      isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with
      high VT (peak airway opening pressure [Pao] of approximately 35 cm H2O) and
      compared them with low VT ventilation (Pao approximately 8 cm H2O), moderate VT
      ventilation (Pao approximately 20 cm H2O), and nonventilated rats. Lung edema
      clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60
      min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01),
      but did not change after low VT and moderate VT ventilation at any time point.
      Lung permeability to small (22Na+, [3H]mannitol) and large solutes (fluorescein
      isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats
      ventilated for 60 min with high VT, compared with low VT, moderate VT, and
      control rats (p < 0.01). Paralleling the impairment in lung edema clearance we
      found a decrease in Na,K-ATPase activity in alveolar type II (ATII) cells
      isolated from rats ventilated with moderate VT and high VT for 40 min without
      changes in alpha1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to
      clear edema by inhibiting active sodium transport and Na,K-ATPase function in the
      alveolar epithelium.

PMID- 9927380
TI  - Contaminated aerosol recovery from pulmonary function testing equipment.
AB  - Clinically, the spread of infectious agents between subjects undergoing
      spirometry is quite uncommon. There is almost no documentation in the medical
      literature on this subject. We studied the retrieval of nonpathogenic Escherichia
      coli after aerosolizing organisms into standard pulmonary function tubing of a
      type that is frequently used by volume-sensing spirometers. The arrival of the
      aerosol at the distal end of the tubing was documented by culture. After delays
      of 0, 1, 5, and 10 min, respectively, air was forcibly withdrawn from the
      proximal end of the tubing through a special petri plate assembly. The plates
      were cultured and the colonies were counted. Immediately after insufflation of
      organisms, air withdrawn from the proximal tubing had counts similar to the air
      sampled at the distal end. After a 1-min delay, the proximal samples contained
      only rare organisms. No organisms were recovered from proximal air samples after
      a delay of 5 or 10 min after insufflation of organisms. The absence of detectable
      aerosolized E. coli after delays of 5 and 10 min after insufflation of organisms
      into spirometry tubing supports the hypothesis that a significant transfer of
      aerosolized organisms does not occur during routine pulmonary function testing as
      long as an interval of 5 min or more is allowed between tests.

PMID- 9927381
TI  - Dioleylphosphatidylglycerol inhibits the expression of type II phospholipase A2
      in macrophages.
AB  - We have recently shown that modified natural pulmonary surfactant Curosurf
      inhibits the synthesis of type II phospholipase A2 (sPLA2-II) by cultured guinea
      pig alveolar macrophages (AM). The goal of the present study was to identify the
      surfactant components and the mechanisms involved in this process. We show that
      protein-free artificial surfactant (AS) mimicked the inhibitory effect of
      Curosurf, suggesting that phospholipid components of surfactant play a role in
      the inhibition of sPLA2-II expression. Among surfactant phospholipids,
      dioleylphosphatidylglycerol (DOPG) was the most effective in inhibiting the
      synthesis of sPLA2-II. By contrast, the concentrations of platelet-activating
      factor (PAF)-acetylhydrolase and lysophospholipase activities remained unchanged,
      indicating that inhibition of sPLA2-II synthesis was caused by a specific effect
      of surfactant. The effect of DOPG on sPLA2-II synthesis was concentration
      dependent and was accompanied by a rapid and time-dependent uptake of DOPG by AM
      whereas dipalmitoylphosphatidylcholine (DPPC) was only marginally taken up.
      Curosurf, AS, and DOPG inhibited tumor necrosis factor-alpha (TNF-alpha)
      secretion, a key step in the induction of sPLA2-II synthesis by AM, in contrast
      to DPPC which had only a marginal effect. We conclude that phospholipid
      components, especially DOPG, play a major role in the inhibition of sPLA2-II
      synthesis by surfactant and that this effect can be explained, at least in part,
      by an impairment of TNF-alpha secretion.

PMID- 9927382
TI  - Segmental antigen challenge increases fibronectin in bronchoalveolar lavage
      fluid.
AB  - Fibronectin may contribute to asthma pathogenesis by recruitment and activation
      of inflammatory cells, and by promotion of subepithelial fibrosis. Fibronectin is
      produced by several types of airway cells, including epithelial cells,
      fibroblasts, and alveolar macrophages. To test the hypothesis that antigen
      induced airway inflammation is associated with increased local generation of
      fibronectin, segmental bronchoprovocation (SBP) with antigen and saline was
      performed in 17 atopic patients. Bronchoalveolar lavage (BAL) was performed at 5
      min and 48 h after segmental challenge with saline or antigen. Fibronectin
      concentrations in BAL fluid, measured by enzyme-linked immunosorbent assay
      (ELISA), increased more than 5-fold 48 h after antigen challenge (65 [47 to 110]
      versus 407 [240 to 697] ng/ml, median and 25 to 75% interquartiles, p < 0.05).
      Fibronectin concentrations 48 h after antigen challenge correlated with histamine
      concentrations 5 min after antigen challenge and numbers of eosinophils,
      neutrophils, macrophages, and total cells in BAL fluid 48 h after antigen
      challenge. BAL was more enriched in fibronectin 48 h after challenge than would
      be predicted solely from increased permeability of plasma proteins. Western blot
      analysis showed that fibronectin in BAL fluid was largely intact and contained
      the extra domain-A (ED-A) splice variant of cellular fibronectin, indicative of
      local production. We conclude that antigen challenge in atopic subjects causes
      increased production of fibronectin by airway cells and speculate that this
      response may contribute to airway remodeling in allergic inflammation.

PMID- 9927383
TI  - Dopamine restores lung ability to clear edema in rats exposed to hyperoxia.
AB  - Exposure to hyperoxia causes lung injury, decreases active sodium transport and
      lung edema clearance in rats. Dopamine (DA) increases lung edema clearance by
      stimulating vectorial Na+ flux and Na, K-ATPase function in rat alveolar
      epithelium. This study was designed to test whether DA (10(-)5 M) would increase
      lung edema clearance in rats exposed to 100% O2 for 64 h. Active Na+ transport
      and lung edema clearance decreased by approximately 44% in rats exposed to acute
      hyperoxia (p < 0.001). DA increased lung edema clearance in room air breathing
      rats (from 0.50 +/- 0.02 to 0.75 +/- 0.06 ml/h) and in rats exposed to 100% O2
      (from 0.28 +/- 0.03 to 0. 67 +/- 0.03 ml/h). Disruption of cell microtubular
      transport system by colchicine blocked the stimulatory effect of DA on active Na+
      transport in control and hyperoxic rats, whereas the isomer beta-lumicolchicine,
      which does not affect cell microtubular transport, did not inhibit the
      stimulatory effects of dopamine. The Na,K-ATPase alpha1-subunit protein abundance
      increased in the basolateral membranes of alveolar type II (ATII) cells incubated
      with 10(-)5 M DA for 15 min, probably by recruiting Na+ pumps from intracellular
      pools. Colchicine, but not beta-lumicolchicine, prevented the recruitment of
      alpha1 subunits to the plasma membrane by DA. Accordingly, DA restored lung
      ability to clear edema in hyperoxic-injured rat lungs. Conceivably, dopamine
      induces recruitment of Na+ pumps from intracellular pools to the plasma membrane
      of alveolar epithelial cells and thus increases lung edema clearance.

PMID- 9927384
TI  - Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial
      cells through p38 mitogen-activated protein kinase.
AB  - The changes in airway osmolarity have been described to contribute to the
      production of exercise- induced bronchoconstriction (EIB) and the development of
      the late-phase response (LPR). The mechanism has been investigated; however, the
      responsiveness of bronchial epithelial cells (BEC) to hyperosmolarity and the
      intracellular signals leading to cell activation have not been determined. In
      this study, we examined the effect of hyperosmolar medium on interleukin-8 (IL-8)
      expression and the role of p38 mitogen-activated protein (MAP) kinase and c-Jun
      NH2 terminal kinase ( JNK) in human BEC in this response in order to clarify the
      intracellular signals regulating IL-8 expression in hyperosmolarity-stimulated
      BEC. The results showed that hyperosmolarity induced IL-8 expression in a
      concentration dependent manner, p38 MAP kinase phosphorylation and activation,
      and JNK activation whether NaCl or mannitol was used as the solute. SB 203580 as
      the specific p38 MAP kinase inhibitor inhibited hyperosmolarity-induced p38 MAP
      kinase activation and partially inhibited hyperosmolarity-induced IL-8
      expression. These results indicate that p38 MAP kinase, at least in part,
      regulates hyperosmolarity-induced IL-8 expression in BEC. However, other signals
      such as JNK are possibly also involved. These results provide new evidence on the
      mechanism responsible for the development of the LPR induced by EIB, and a
      strategy for treatment with the specific p38 MAP kinase inhibitor.

PMID- 9927385
TI  - Volume of graft and native lung after single-lung transplantation for emphysema.
AB  - To assess how the presence of the hyperinflated native lung influences the volume
      of the graft after single-lung transplantation (SLT) for emphysema, we used chest
      computed tomography to measure the TLC of each lung at a mean of 326 d before and
      239, 588, and 932 d after SLT in nine patients. In addition, we obtained
      measurements of TLC and FRC in these nine patients plus one additional recipient
      at 697 d after surgery, and in 10 nonsmoking normal subjects matched for age,
      sex, height, and weight. On the nontransplanted side, TLC averaged 3.57 L before
      and 3.73 L, 3.70 L, and 3.73 L after SLT (NS). Corresponding values on the
      transplanted side were 3.42 L before and 2.06 L, 1.96 L, and 1.90 L after
      surgery, respectively (p < 0. 0002). Compared with the values obtained on the
      ipsilateral side in the control subjects, the FRC of the graft amounted to 100%,
      but its TLC was decreased to 79% (p < 0.005). We conclude that (1) the TLC of the
      graft and of the native lung do not change over time after SLT for emphysema, and
      (2) compared with the ipsilateral lung in normal control subjects, the TLC of the
      graft is substantially reduced, but its FRC is within normal limits.

PMID- 9927386
TI  - Lung epithelium-specific proteins: characteristics and potential applications as
      markers.

PMID- 9927388
TI  - Benefits of strict glucose and blood pressure control in type 2 diabetes: lessons
      from the UK Prospective Diabetes Study.

PMID- 9927387
TI  - NHLBI Workshop Summary. Report of workshop on lymphangioleiomyomatosis. National
      Heart, Lung, and Blood Institute.

PMID- 9927389
TI  - Stroke in women: the 1997 Paul Dudley White International Lecture.

PMID- 9927390
TI  - Appreciating alpha-adrenergic receptors and their role in ischemic left
      ventricular dysfunction.

PMID- 9927391
TI  - P-Glycoprotein in clinical cardiology.

PMID- 9927392
TI  - Delayed response of myocardial flow reserve to lipid-lowering therapy with
      fluvastatin.
AB  - BACKGROUND: Lipid-lowering therapy can improve endothelial function in patients
      with coronary artery disease (CAD) and hypercholesterolemia. Little is known
      about induced changes in myocardial microcirculation. This study prospectively
      investigated the temporal effects of lipid-lowering therapy with fluvastatin on
      coronary flow and flow reserve (CFR) in patients with CAD assessed by PET.
      METHODS AND RESULTS: In an open clinical trial, CFR was studied in 15 patients
      with angiographically documented multivessel CAD and hypercholesterolemia (LDL
      >160 mg/dL). Dynamic 13N-labeled ammonia PET imaging in conjunction with
      adenosine was used to assess regional and global CFR at baseline as well as at 2
      and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid
      decrease in total cholesterol (29+/-6%) and LDL (37+/-9%), myocardial blood flow
      at rest and during stress was unchanged after 2 months of treatment (2.7+/-0.9
      versus 2.5+/-0.6 mL x g-1 x min-1). At 6 months, stress blood flow as well as CFR
      increased significantly (3.4+/-1.0 mL x g-1 x min-1). No change in hemodynamic
      parameters was noted during the entire study. Nine of 15 patients increased CFR
      by >20%. All responders demonstrated improvement in anginal symptoms, whereas
      nonresponders stated no change (n=4) or worsening of symptoms (n=2). The
      improvement in CFR was not related to the amount of lipid lowering and was
      independent of the severity of stenoses. CONCLUSIONS: Improvement in stress blood
      flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin,
      suggesting a slow recovery of the vasodilatory response to adenosine.

PMID- 9927393
TI  - Alpha-adrenergic blockade improves recovery of myocardial perfusion and function
      after coronary stenting in patients with acute myocardial infarction.
AB  - BACKGROUND: AMI reperfusion by thrombolysis does not improve TIMI flow and LV
      function. The role of infarct-related artery (IRA) stenosis and superimposed
      changes in coronary vasomotor tone in maintaining LV dysfunction must be
      elucidated. METHODS AND RESULTS: Forty patients underwent diagnostic angiography
      24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit
      lesion was dilated with coronary stenting. During angioplasty, LV function was
      monitored by transesophageal echocardiography. Percent regional systolic
      thickening was quantitatively assessed before PTCA, soon after stenting, 15
      minutes after stenting, and after phentolamine 12 microg/kg IC (n=10), the alpha1
      blocker urapidil 600 microg/kg IV (n=10), or saline (n=10). Ten patients
      pretreated with beta-blockers received urapidil 10 mg IC. Coronary stenting
      significantly improved thickening in IRA-dependent and in non-IRA-dependent
      myocardium (from 27+/-15% to 38+/-16% and from 40+/-15% to 45+/-15%,
      respectively). Simultaneously, TIMI frame count decreased from 39+/-11 and 40+/
      11 in the IRA and non-IRA, respectively, to 23+/-10 and 25+/-7 (P<0.05). Fifteen
      minutes after stenting, thickening worsened in both IRA- and non-IRA-dependent
      myocardium (to 19+/-14% and 28+/-14%, P<0.05), and TIMI frame count returned, in
      both the IRA and non-IRA, to the values obtained before stenting. Phentolamine
      and urapidil increased thickening to 36+/-17% and 41+/-14% in IRA and to 48+/-11%
      and 49+/-17% in non-IRA myocardium respectively, and TIMI frame count decreased
      to 16+/-6 and to 17+/-5, respectively. Changes were attenuated with beta-blocker
      pretreatment. CONCLUSIONS: Our finding that alpha-adrenergic blockade attenuates
      vasoconstriction and postischemic LV dysfunction supports the hypothesis of an
      important role of neural mechanisms in this phenomenon.

PMID- 9927394
TI  - L-Arginine normalizes coronary vasomotion in long-term smokers.
AB  - BACKGROUND: Noninvasive measurements of myocardial blood flow (MBF) with PET
      revealed an abnormal coronary vasomotor response to cold pressor test in healthy
      long-term smokers. If coronary endothelial dysfunction accounted for this
      abnormality, we hypothesized that it could be reversed by L-arginine as the
      substrate for NO synthase. METHODS AND RESULTS: MBF was quantified with 13N
      labeled ammonia and PET in 11 healthy smokers (age, 45+/-10 years; 27+/-10 years
      of smoking) and in 12 age-matched nonsmokers on 2 separate days. On day 1, MBF
      was measured at rest and, after intravenous L-arginine, during cold pressor test.
      On day 2, MBF was measured during cold pressor test and then at rest during L
      arginine. Baseline rate-pressure product (RPP) (6559+/-1590 versus 7144+/-1157
      bpmxmm Hg) and MBF (0.65+/-0.14 versus 0.73+/-0.13 mL x g-1 x min-1) were similar
      in nonsmokers and smokers. Cold pressor test increased RPP similarly in both
      groups (53+/-26% versus 46+/-26%), whereas MBF increased in nonsmokers (to 0.93+/
      0.25 mL x g-1 x min-1; P<0.05) but not in smokers (0.80+/-0.16 mL x g-1 x min-1).
      The percent MBF increase differed between nonsmokers and smokers (44+/-25% versus
      11+/-14%; P=0.0017). However, after L-arginine, the magnitude of MBF response to
      cold pressor test no longer differed between groups (48+/-36% versus 48+/-28%),
      whereas RPP again increased similarly in the 2 groups (59+/-30% versus 44+/-16%).
      L-Arginine had no effect on resting MBF in smokers or nonsmokers. CONCLUSIONS:
      Our findings implicate the coronary endothelium as the major site of the abnormal
      vasomotor response in long-term smokers. Cold pressor test combined with PET
      imaging may allow the noninvasive identification of coronary endothelial
      dysfunction in humans.

PMID- 9927395
TI  - Delayed treatment of traumatic rupture of the thoracic aorta with endoluminal
      covered stent.
AB  - BACKGROUND: Stent grafting is emerging as a new treatment for several
      pathological conditions involving the thoracic aorta. We studied the feasibility
      and safety of this technique for delayed treatment of ruptures of the aortic
      isthmus. METHODS AND RESULTS: Nine patients (14 to 76 years old; mean, 37 years;
      male/female ratio, 8/1) underwent stent grafting of the aortic isthmus in
      subacute (n=5) or chronic (n=4) aortic traumatic rupture after a motor accident.
      In subacute ruptures, this treatment was delayed (1 to 8 months; mean, 5.4
      months) because of the severity of other associated injuries. Stent grafting was
      technically successful (defined as complete exclusion of the pseudoaneurysmal
      sac) in all patients. Short-term fever and biological inflammatory syndrome
      occurred in 3 patients. Two major complications occurred: in 1 patient, an early
      occlusion of the left subclavian artery was treated by placement of 2 Palmaz
      stents. In another patient, an atelectasis related to an increase of preexisting
      compression of the left main bronchus by the pseudoaneurysmal sac was
      successfully treated by temporary placement of an endobronchial silicone stent.
      Mean follow-up was 11.6 months (range, 3 to 21 months). Thrombosis of the
      pseudoaneurysmal sac was found in all patients. CONCLUSIONS: In the absence of
      available extended follow-up about the safety and effectiveness of endovascular
      grafting, this approach seems to be a viable therapeutic option for traumatic
      rupture of the aortic isthmus, but appropriately controlled prospective studies
      are needed before we can recommend its widespread use.

PMID- 9927396
TI  - Protein kinase A (PKA)-dependent troponin-I phosphorylation and PKA regulatory
      subunits are decreased in human dilated cardiomyopathy.
AB  - BACKGROUND: Most studies indicate that failing human hearts have greater baseline
      myofibrillar Ca2+ sensitivity of tension development than nonfailing hearts.
      Phosphorylation of cardiac troponin I (TnI) by cAMP-dependent protein kinase
      (PKA) decreases the affinity of the troponin complex for Ca2+, thus altering the
      Ca2+ sensitivity of force production. We tested the hypothesis that PKA-dependent
      TnI phosphorylation is altered in the failing human heart and investigated
      changes in PKA regulatory subunits as a potential mechanism. METHODS AND RESULTS:
      Using in vitro back-phosphorylation with [gamma-32P]ATP, we demonstrated a
      significant (P<0.05) approximately 25% reduction in baseline PKA-dependent TnI
      phosphorylation in human hearts with dilated cardiomyopathy (DCM) compared with
      nonfailing (NF) human hearts. There was no significant difference in cAMP content
      or maximal PKA activity between DCM and NF hearts, but expression of the
      regulatory subunits of PKA-I (RI) and PKA-II (RII) was significantly decreased in
      DCM versus NF hearts (RI by approximately 40%, P<0.05; RII by approximately 30%,
      P<0.01). CONCLUSIONS: PKA activity is regulated at the substrate level through
      interactions of PKA regulatory subunits with A-kinase anchoring proteins. The
      reduced baseline PKA-dependent phosphorylation of TnI in DCM may be due to
      decreased expression of RI and RII and consequently reduced anchoring of PKA
      holoenzyme. These findings provide new evidence of deficiencies in downstream
      regulation of the beta-adrenergic pathway in the failing human heart and may
      account for increased baseline myofibrillar Ca2+ sensitivity.

PMID- 9927397
TI  - Left ventricular diastolic function in normal human pregnancy.
AB  - BACKGROUND: Little information is available about changes in left ventricular
      diastolic function during pregnancy. We used mitral inflow and pulmonary venous
      flow profiles to evaluate left ventricular diastolic function in 37 healthy
      pregnant women 26 to 41 years old (mean, 32 years). METHODS AND RESULTS:
      Echocardiographic studies were performed at the end of each trimester. Eight
      subjects (control group) underwent similar testing 1 to 3.5 months (mean, 1.7
      months) postpartum. During pregnancy, the cardiac output increased significantly
      as a result of an increased heart rate and, to a lesser degree, stroke volume.
      Significantly decreased systemic vascular resistance and increased left
      ventricular mass were also noted. Peak mitral flow velocity in early diastole (E)
      increased 13. 3% during the first trimester and remained at the high end of
      normal throughout pregnancy. Peak A-wave velocity (A) increased maximally in the
      third trimester. Compared with control subjects, first-trimester subjects had a
      significantly increased E/A ratio. The ratio subsequently decreased, reflecting
      the augmented A-wave velocity. Pulmonary venous peak systolic forward flow
      velocity increased, peaking in the second trimester (nonsignificant), but
      returned to baseline levels postpartum. The pulmonary venous diastolic time
      velocity integral decreased significantly from the first to the third trimester.
      Peak pulmonary venous reverse flow velocity at atrial contraction increased
      significantly, without being markedly changed in duration. CONCLUSIONS:
      Pregnancy, a chronic, natural volume-overload state, has important effects on
      hemodynamic and echocardiographic variables. Based on pulmonary venous flow and
      left ventricular inflow velocities, our results provide a standard reference
      concerning diastolic filling dynamics by trimester.

PMID- 9927399
TI  - Low penetrance in the long-QT syndrome: clinical impact.
AB  - BACKGROUND: It is still currently held that most patients affected by the long-QT
      syndrome (LQTS) show QT interval prolongation or clinical symptoms. This is
      reflected by the assumption in linkage studies of a penetrance of 90%. We had
      previously suggested that a larger-than-anticipated number of LQTS patients might
      be affected without showing clinical signs. We have now exploited the
      availability of molecular diagnosis to test this hypothesis. METHODS AND RESULTS:
      We identified 9 families with "sporadic" cases of LQTS, ie, families in which,
      besides the proband, none of the family members had clinical signs of the
      disease. Mutation screening by conventional single-strand conformational
      polymorphism and sequencing was performed on DNA of probands and family members
      to identify mutation carriers. Of 46 family members considered on clinical
      grounds to be nonaffected, 15 (33%) were found instead to be gene carriers.
      Penetrance was found to be 25%. In these families, conventional clinical
      diagnostic criteria had a sensitivity of only 38% in correctly identifying
      carriers of the genetic defect. CONCLUSIONS: This study demonstrates that in some
      families, LQTS may appear with a very low penetrance, a finding with multiple
      clinical implications. The family members considered to be normal and found to be
      silent gene carriers are unexpectedly at risk of generating affected offspring
      and also of developing torsade de pointes if exposed to either cardiac or
      noncardiac drugs that block potassium channels. It is no longer acceptable to
      exclude LQTS among family members of definitely affected patients on purely
      clinical grounds. Conversely, it now appears appropriate to perform molecular
      screening in all family members of genotyped patients.

PMID- 9927398
TI  - Genetic and molecular basis of cardiac arrhythmias: impact on clinical management
      parts I and II.
AB  - Genetic approaches have succeeded in defining the molecular basis of an
      increasing array of heart diseases, such as hypertrophic cardiomyopathy and the
      long-QT syndromes, associated with serious arrhythmias. Importantly, the way in
      which this new knowledge can be applied to managing patients and to the
      development of syndrome-specific antiarrhythmic strategies is evolving rapidly
      because of these recent advances. In addition, the extent to which new knowledge
      represents a purely research tool versus the extent to which it can be applied
      clinically is also evolving. The present article represents a consensus report of
      a meeting of the European Working Group on Arrhythmias. The current state of the
      art of the molecular and genetic basis of inherited arrhythmias is first
      reviewed, followed by practical advice on the role of genetic testing in these
      and other syndromes and the way in which new findings have influenced current
      understanding of the molecular and biophysical basis of arrhythmogenesis.

PMID- 9927400
TI  - Radiofrequency catheter ablation of common atrial flutter: significance of
      palpitations and quality-of-life evaluation in patients with proven isthmus
      block.
AB  - BACKGROUND: Creation of a complete bidirectional inferior vena cava-tricuspid
      annulus isthmus block (CBIB) by radiofrequency catheter ablation is now a well
      accepted criterion for prevention of common atrial flutter (AFl) recurrences.
      However, some patients still complain of palpitations after ablation, and it is
      not known whether these are related to AFl recurrences or to other arrhythmias.
      METHODS AND RESULTS: Among 100 consecutive patients referred to our institution
      for AFl ablation, CBIB was created in 83. There were 54 patients (group A) in
      whom AFl was the only documented arrhythmia before ablation and 29 patients
      (group B) in whom atrial fibrillation (AFib) had been documented in addition to
      AFl. An electrophysiological control study was performed in 40 patients 1 to 3
      months after ablation. Arrhythmic events, medications, and functional status were
      evaluated at midterm follow-up (n=77; 14. 7+/-8.4 months; range, 4 to 34 months).
      The SF-36 questionnaire and the Symptom Checklist--Frequency and Severity Scale
      specific for cardiac arrhythmia were used to assess quality of life in 63
      patients at long-term follow-up (27.1+/-8.5 months). Recurrence of AFl was
      documented in only 1 patient 6 months after ablation. AFib was recorded in 28
      patients (36.4%), and atypical AFl was found in 3 patients. Thirty-two group A
      patients (66.7%) and 17 group B patients (58.6%) were still arrhythmia free at
      midterm follow-up. Even at long-term follow-up and in group B patients, AFl
      ablation was followed by a clear improvement in quality of life. CONCLUSIONS:
      Palpitations after creation of CBIB are due mostly to AFib but not to AFl
      recurrence. This technique provides a significant and persistent clinical benefit
      and may suppress all atrial arrhythmia in a subset of patients suffering from
      both AFl and AFib.

PMID- 9927401
TI  - Association of body fat distribution and cardiovascular risk factors in children
      and adolescents.
AB  - BACKGROUND: Obesity is associated with increased risk of cardiovascular disease
      in adults and less favorable cardiovascular risk factor status in children and
      adolescents. In adults, fat distribution has been shown to be related to lipid
      and lipoprotein concentrations, blood pressure levels, and left ventricular mass.
      These relationships have not been extensively studied in young subjects. METHODS
      AND RESULTS: This was a cross-sectional study of 127 children and adolescents 9
      to 17 years of age. Dual-energy x-ray absorptiometry was used to measure total
      and regional fat mass. The dependent variables were fasting lipid and lipoprotein
      concentrations, systolic and diastolic blood pressures, and left ventricular
      mass. There were significant (P<0.05) univariate correlations between fat
      distribution and log triglycerides (r=0.27), log HDL cholesterol (r=-0.23),
      systolic blood pressure (r=0.26), and left ventricular mass (r=0.37). Multiple
      regression analysis showed that the significant independent correlates for
      triglycerides and HDL cholesterol were age and fat distribution; for systolic
      blood pressure, height and fat distribution; and for left ventricular mass,
      height, race, sex, and fat distribution. CONCLUSIONS: These results demonstrate
      that fat distribution is a more important independent correlate of cardiovascular
      risk factors than percent body fat in children and adolescents. Greater
      deposition of central fat (an android fat pattern) is associated with less
      favorable plasma lipid and lipoprotein concentrations, blood pressure, and left
      ventricular mass.

PMID- 9927402
TI  - Cardiac myocytes produce interleukin-6 in culture and in viable border zone of
      reperfused infarctions.
AB  - BACKGROUND: Previous work from our laboratory demonstrated that interleukin (IL)
      6 plays a potentially critical role in postreperfusion myocardial injury and is
      the major cytokine responsible for induction of intracellular adhesion molecule
      (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is
      necessary for neutrophil-associated myocyte injury. We have previously
      demonstrated the induction of IL-6 in the ischemic myocardium, and the current
      study addresses the cells of origin of IL-6. METHODS AND RESULTS: In the present
      study, we combined Northern blot analysis and in situ hybridization to
      demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular
      myocytes were stimulated with tumor necrosis factor-alpha, IL-1beta,
      lipopolysaccharide, preischemic lymph, and postischemic lymph. Unstimulated
      myocytes showed no significant IL-6 mRNA expression. Myocytes stimulated with
      preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes
      stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, or
      postischemic lymph showed a strong IL-6 mRNA induction. Northern blot with ICAM-1
      probe revealed ICAM-1 expression under every condition that demonstrated IL-6
      induction. We then investigated the expression of IL-6 mRNA in our canine model
      of ischemia and reperfusion. Cardiac myocytes in the viable border zone of a
      myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA
      within 1 hour after reperfusion. Mononuclear cells infiltrate the border zone and
      express IL-6 mRNA. CONCLUSIONS: Isolated cardiac myocytes produce IL-6 mRNA in
      response to several cytokines as well as postischemic cardiac lymph. In addition
      to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced
      in myocytes in the viable border zone of a myocardial infarct. The potential
      roles of IL-6 in cardiac myocytes in an infarct border are discussed.

PMID- 9927403
TI  - Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to
      explain the interaction between digoxin and quinidine [seecomments].
AB  - BACKGROUND: Although quinidine is known to elevate plasma digoxin concentrations,
      the mechanism underlying this interaction is not fully understood. Digoxin is not
      extensively metabolized, but it is known to be transported by the drug efflux
      pump P-glycoprotein, which is expressed in excretory tissues (kidney, liver,
      intestine) and at the blood-brain barrier. Accordingly, we tested the hypothesis
      that inhibition of P-glycoprotein-mediated digoxin transport by quinidine
      contributes to the digoxin-quinidine interaction. METHODS AND RESULTS: First, we
      demonstrated active transcellular transport of both digoxin and quinidine in
      cultured cell lines that express P-glycoprotein in a polarized fashion. In
      addition, 5 micromol/L quinidine inhibited P-glycoprotein-mediated digoxin
      transport by 57%. Second, the effect of quinidine on digoxin disposition was
      studied in wild-type and in mdr1a(-/-) mice, in which the gene expressing the
      major digoxin-transporting P-glycoprotein has been disrupted. Because the in
      vitro data showed that quinidine itself is a P-glycoprotein substrate, quinidine
      doses were reduced in mdr1a(-/-) mice to produce plasma concentrations similar to
      those in wild-type control animals. Quinidine increased plasma digoxin
      concentrations by 73.0% (P=0.05) in wild-type animals, compared with 19.5% (P=NS)
      in mdr1a(-/-) mice. Moreover, quinidine increased digoxin brain concentrations by
      73.2% (P=0.05) in wild-type animals; by contrast, quinidine did not increase
      digoxin brain concentrations in mdr1a(-/-) mice but rather decreased them (
      30.7%, P<0.01). CONCLUSIONS: Quinidine and digoxin are both substrates for P
      glycoprotein, and quinidine is a potent inhibitor of digoxin transport in vitro.
      The in vivo data strongly support the hypothesis that inhibition of P
      glycoprotein-mediated digoxin elimination plays an important role in the increase
      of plasma digoxin concentration occurring with quinidine coadministration in wild
      type mice and thus support a similar mechanism in humans.

PMID- 9927404
TI  - Coronary arteriolar dilation to acidosis: role of ATP-sensitive potassium
      channels and pertussis toxin-sensitive G proteins.
AB  - BACKGROUND: We previously demonstrated that coronary arteriolar dilation in
      response to acidosis is mediated by the opening of ATP-sensitive potassium (KATP)
      channels. However, the signal transduction involved in the KATP-channel
      activation during acidosis has not been elucidated. A recent study in cardiac
      myocytes implied that pertussis toxin (PTX)-sensitive G proteins may be involved
      in the signal transduction for KATP-channel activation. However, it remains
      unclear whether this transduction process also occurs in the vascular tissue and,
      in particular, whether it exerts functional dilation in response to acidosis.
      METHODS AND RESULTS: To examine the signaling pathway for acidosis-induced
      dilation, porcine coronary arterioles were isolated, cannulated, and pressurized
      for in vitro study. The GTPase activity in reconstituted G proteins was examined
      at different levels of pH. Extravascular acidosis (pH 7.3 to 7.0) produced a
      graded dilation of coronary arterioles. This dilation was not affected by removal
      of endothelium but was significantly attenuated after inhibition of KATP channels
      and G proteins by glibenclamide and PTX, respectively. Glibenclamide and PTX
      attenuated the acidosis-induced arteriolar dilation to the same extent, and
      combined administration of both inhibitors did not further inhibit the
      vasodilation. These results indicated that both inhibitors act on the same
      vasodilatory pathway. Furthermore, vasodilation of coronary arterioles to the
      KATP-channel opener pinacidil and to the endothelium-independent vasodilator
      sodium nitroprusside was not affected by PTX. Because PTX inhibited acidosis
      induced vasodilation without inhibiting KATP-channel function, it is suggested
      that PTX inhibits the vasodilatory pathway upstream from KATP channels. GTPase
      activity in reconstituted G proteins was significantly enhanced by a reduction in
      pH, indicating that G proteins were directly activated by acidosis. CONCLUSIONS:
      On the basis of these findings, we conclude that acidosis-induced coronary
      arteriolar dilation is mediated by the opening of smooth muscle KATP channels
      through the activation of PTX-sensitive G proteins.

PMID- 9927405
TI  - PDGFbeta receptor blockade inhibits intimal hyperplasia in the baboon.
AB  - BACKGROUND: We have evaluated the use of a mouse/human chimeric anti-platelet
      derived growth factor-beta receptor antibody in combination with heparin to
      inhibit intimal hyperplasia in the saphenous artery of the baboon after balloon
      angioplasty. METHODS AND RESULTS: The study evaluated lesion development in
      sequential injuries made 28 days apart. Each animal received control treatment
      after the first injury and antibody/heparin therapy after the second injury to
      the contralateral artery. The antibody was administered by bolus intravenous
      injections (10 mg/kg) on study days 1, 4, 8, 15, and 22 and heparin
      coadministered by continuous intravenous infusion at a dose of 0.13 mg/kg per
      hour. Morphometric analysis of tissue sections showed a 53% decrease in intimal
      area after antibody/heparin treatment (P=0.005), corresponding to a 40% decrease
      in the intima-to-media ratio (P=0.005). Smooth muscle cell proliferation in the
      injured wall, measured at both 4 and 29 days after balloon injury, were similar
      in the control and antibody/heparin-treated animals. CONCLUSIONS: These data
      suggest that platelet-derived growth factor plays a key role in the development
      of intimal lesions at sites of acute vascular injury in the nonhuman primate.

PMID- 9927407
TI  - Glucose for the heart.

PMID- 9927406
TI  - Effects of a specific endothelin-converting enzyme inhibitor on cardiac, renal,
      and neurohumoral functions in congestive heart failure: comparison of effects
      with those of endothelin A receptor antagonism.
AB  - BACKGROUND--Endothelin (ET)-1 is generated from big ET-1 by endothelin-converting
      enzyme (ECE). Plasma big ET-1 and ET-1 levels are strongly related to survival in
      patents with congestive heart failure (CHF). Because selective enzymatic
      processing of ET-1 formation appears to be an important therapeutic target for
      CHF, we investigated the acute effects of a specific ECE inhibitor on cardiorenal
      and endocrine functions in CHF compared with those of a selective ETA receptor
      antagonist. METHODS AND RESULTS--CHF was induced in beagle dogs by rapid right
      ventricular pacing (270 bpm, 14 days). Two incremental doses of a specific ECE
      inhibitor, FR901533, or a selective ETA receptor antagonist, FR139317 (1 and 3
      mg/kg, n=8, respectively), were injected into dogs with CHF. FR901533 and
      FR139317 decreased mean arterial pressure and pulmonary capillary wedge pressure
      associated with reduction in systemic and pulmonary vascular resistance. These
      agents increased cardiac output but did not affect left ventricular fractional
      shortening. FR139317 exerted a greater depressor effect on mean arterial pressure
      than FR901533 (P<0.05). These agents decreased plasma atrial natriuretic peptide
      levels, but only FR901533 decreased plasma renin activity, angiotensin II, and
      aldosterone levels. Neither agent changed the plasma norepinephrine level despite
      the fall in blood pressure. These drugs increased the urinary water and sodium
      excretion rate associated with increases in the glomerular filtration rate and
      renal plasma flow, and the incremental magnitude induced by FR139317 was larger
      than that by FR901533 (P<0.05). CONCLUSIONS--An ETA receptor antagonist appeared
      to induce greater vasodilative effects on systemic and renal vasculature in CHF
      than an ECE inhibitor. However, the ECE inhibitor reduced the secretion of
      neurohumoral factors that are activated in proportion to the severity of CHF. Our
      acute complementary data may support the importance of the role of ECE in CHF and
      provide a rationale foundation for investigating the usefulness of long-term
      treatment with ECE inhibitors in CHF.

PMID- 9927408
TI  - Images in cardiovascular medicine. Reactive hyperemia after release of coronary
      spasm.

PMID- 9927409
TI  - AHA Science Advisory. Antioxidant consumption and risk of coronary heart disease:
      emphasison vitamin C, vitamin E, and beta-carotene: A statement for healthcare
      professionals from the American Heart Association.

PMID- 9927411
TI  - An ATP-driven efflux pump is a novel pathogenicity factor in rice blast disease.
AB  - Cells tolerate exposure to cytotoxic compounds through the action of ATP-driven
      efflux pumps belonging to the ATP-binding cassette (ABC) superfamily of membrane
      transporters. Phytopathogenic fungi encounter toxic environments during plant
      invasion as a result of the plant defense response. Here we demonstrate the
      requirement for an ABC transporter during host infection by the fungal plant
      pathogen Magnaporthe grisea. The ABC1 gene was identified in an insertional
      mutagenesis screen for pathogenicity mutants. The ABC1 insertional mutant and a
      gene-replacement mutant arrest growth and die shortly after penetrating either
      rice or barley epidermal cells. The ABC1-encoded protein is similar to yeast ABC
      transporters implicated in multidrug resistance, and ABC1 gene transcripts are
      inducible by toxic drugs and a rice phytoalexin. However, abc1 mutants are not
      hypersensitive to antifungal compounds. The non-pathogenic, insertional mutation
      in ABC1 occurs in the promoter region and dramatically reduces transcript
      induction by metabolic poisons. These data strongly suggest that M.grisea
      requires the up-regulation of specific ABC transporters for pathogenesis; most
      likely to protect itself against plant defense mechanisms.

PMID- 9927410
TI  - Leukocyte polarization in cell migration and immune interactions.
AB  - Cell migration plays a key role in a wide variety of biological phenomena. This
      process is particularly important for leukocyte function and the inflammatory
      response. Prior to migration leukocytes undergo polarization, with the formation
      of a lamellipodium at the leading edge and a uropod at the trailing edge. This
      cell shape allows them to convert cytoskeletal forces into net cell-body
      displacement. Leukocyte chemoattractants, including chemokines, provide
      directional cues for leukocyte motility, and concomitantly induce polarization.
      Chemoattractant receptors, integrins and other adhesion molecules, cytoskeletal
      proteins and intracellular regulatory molecules change their cellular
      localization during cell polarization. A complex system of signal transduction
      molecules, including tyrosine kinases, lipid kinases, second messengers and
      members of the Rho family of small GTPases is thought to regulate the
      cytoskeletal rearrangements underlying leukocyte polarization and migration. The
      elucidation of the mechanisms and signals that control this complex
      reorganization will lead to a better understanding of critical questions in cell
      biology of leukocyte migration and polarity.

PMID- 9927413
TI  - Supramolecular organization of the photosynthetic apparatus of Rhodobacter
      sphaeroides.
AB  - Native tubular membranes were purified from the purple non-sulfur bacterium
      Rhodobacter sphaeroides. These tubular structures contain all the membrane
      components of the photosynthetic apparatus, in the relative ratio of one
      cytochrome bc1 complex to two reaction centers, and approximately 24
      bacteriochlorophyll molecules per reaction center. Electron micrographs of
      negative-stained membranes diffract up to 25 A and allow the calculation of a
      projection map at 20 A. The unit cell (a = 198 A, b = 120 A and gamma = 103
      degrees) contains an elongated S-shaped supercomplex presenting a pseudo-2-fold
      symmetry. Comparison with density maps of isolated reaction center and light
      harvesting complexes allowed interpretation of the projection map. Each
      supercomplex is composed of light-harvesting 1 complexes that take the form of
      two C-shaped structures of approximately 112 A in external diameter, facing each
      other on the open side and enclosing the two reaction centers. The remaining
      positive density is tentatively attributed to one cytochrome bc1 complex. These
      features shed new light on the association of the reaction center and the light
      harvesting complexes. In particular, the organization of the light-harvesting
      complexes in C-shaped structures ensures an efficient exchange of
      ubihydroquinone/ubiquinone between the reaction center and the cytochrome bc1
      complex.

PMID- 9927412
TI  - Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial
      genetic and metabolic stress: a novel mode of inter-organelle crosstalk.
AB  - We have investigated the mechanism of mitochondrial-nuclear crosstalk during
      cellular stress in mouse C2C12 myocytes. For this purpose, we used cells with
      reduced mitochondrial DNA (mtDNA) contents by ethidium bromide treatment or
      myocytes treated with known mitochondrial metabolic inhibitors, including
      carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimycin, valinomycin and
      azide. Both genetic and metabolic stresses similarly affected mitochondrial
      membrane potential (Deltapsim) and electron transport-coupled ATP synthesis,
      which was also accompanied by an elevated steady-state cytosolic Ca2+ level
      ([Ca2+]i). The mitochondrial stress resulted in: (i) an enhanced expression of
      the sarcoplasmic reticular ryanodine receptor-1 (RyR-1), hence potentiating the
      Ca2+ release in response to its modulator, caffeine; (ii) enhanced levels of Ca2+
      responsive factors calineurin, calcineurin-dependent NFATc (cytosolic counterpart
      of activated T-cell-specific nuclear factor) and c-Jun N-terminal kinase (JNK)
      dependent ATF2 (activated transcription factor 2); (iii) reduced levels of
      transcription factor, NF-kappaB; and (iv) enhanced transcription of cytochrome
      oxidase Vb (COX Vb) subunit gene. These cellular changes, including the steady
      state [Ca2+]i were normalized in genetically reverted cells which contain near
      normal mtDNA levels. We propose that the mitochondria-to-nucleus stress signaling
      occurs through cytosolic [Ca2+]i changes, which are likely to be due to reduced
      ATP and Ca2+ efflux. Our results indicate that the mitochondrial stress signal
      affects a variety of cellular processes, in addition to mitochondrial membrane
      biogenesis.

PMID- 9927414
TI  - The structure and function of a foot-and-mouth disease virus-oligosaccharide
      receptor complex.
AB  - Heparan sulfate has an important role in cell entry by foot-and-mouth disease
      virus (FMDV). We find that subtype O1 FMDV binds this glycosaminoglycan with a
      high affinity by immobilizing a specific highly abundant motif of sulfated
      sugars. The binding site is a shallow depression on the virion surface, located
      at the junction of the three major capsid proteins, VP1, VP2 and VP3. Two pre
      formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an
      arginine in this virus, is critical to this recognition, forming a key component
      of both sites. This residue is a histidine in field isolates of the virus,
      switching to an arginine in adaptation to tissue culture, forming the high
      affinity heparan sulfate-binding site. We postulate that this site is a conserved
      feature of FMDVs, such that in the infected animal there is a biological
      advantage to low affinity, or more selective, interactions with glycosaminoglycan
      receptors.

PMID- 9927415
TI  - Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins
      with overlapping function.
AB  - ARF proteins, which mediate vesicular transport, have little or no intrinsic
      GTPase activity. They rely on the actions of GTPase-activating proteins (GAPs)
      for their function. The in vitro GTPase activity of the Saccharomyces cerevisiae
      ARF proteins Arf1 and Arf2 is stimulated by the yeast Gcs1 protein, and in vivo
      genetic interactions between arf and gcs1 mutations implicate Gcs1 in vesicular
      transport. However, the Gcs1 protein is dispensable, indicating that additional
      ARF GAP proteins exist. We show that the structurally related protein Glo3, which
      is also dispensable, also exhibits ARF GAP activity. Genetic and in vitro
      approaches reveal that Glo3 and Gcs1 have an overlapping essential function at
      the endoplasmic reticulum (ER)-Golgi stage of vesicular transport. Mutant cells
      deficient for both ARF GAPs cannot proliferate, undergo a dramatic accumulation
      of ER and are defective for protein transport between ER and Golgi. The glo3Delta
      and gcs1Delta single mutations each interact with a sec21 mutation that affects a
      component of COPI, which mediates vesicular transport within the ER-Golgi
      shuttle, while increased dosage of the BET1, BOS1 and SEC22 genes encoding
      members of a v-SNARE family that functions within the ER-Golgi alleviates the
      effects of a glo3Delta mutation. An in vitro assay indicates that efficient
      retrieval from the Golgi to the ER requires these two proteins. These findings
      suggest that Glo3 and Gcs1 ARF GAPs mediate retrograde vesicular transport from
      the Golgi to the ER.

PMID- 9927416
TI  - Identification of MINUS, a small polypeptide that functions as a microtubule
      nucleation suppressor.
AB  - In eukaryotic cells, tubulin polymerization must be regulated precisely during
      cell division and differentiation. To identify new mechanisms involved in
      cellular microtubule formation, we isolated an activity that suppresses
      microtubule nucleation in vitro. The activity was due to a small acidic
      polypeptide of 4.7 kDa which we named MINUS (microtubule nucleation suppressor).
      MINUS inhibited tau- and taxol-mediated microtubule assembly in vitro and was
      inactivated by dephosphorylation. The protein was purified to homogeneity from
      cultured neural (PC12) cells and bovine brain. Microinjection of MINUS caused a
      transient loss of dynamic microtubules in Vero cells. The results suggest that
      MINUS acts with a novel mechanism on tubulin polymerization, thus regulating
      microtubule formation in living cells.

PMID- 9927417
TI  - Regulation of the small GTP-binding protein Rho by cell adhesion and the
      cytoskeleton.
AB  - Soluble factors from serum such as lysophosphatidic acid (LPA) are thought to
      activate the small GTP-binding protein Rho based on their ability to induce actin
      stress fibers and focal adhesions in a Rho-dependent manner. Cell adhesion to
      extracellular matrices (ECM) has also been proposed to activate Rho, but this
      point has been controversial due to the difficulty of distinguishing changes in
      Rho activity from the structural contributions of ECM to the formation of focal
      adhesions. To address these questions, we established an assay for GTP-bound
      cellular Rho. Plating Swiss 3T3 cells on fibronectin-coated dishes elicited a
      transient inhibition of Rho, followed by a phase of Rho activation. The
      activation phase was greatly enhanced by serum. In serum-starved adherent cells,
      LPA induced transient Rho activation, whereas in suspended cells Rho activation
      was sustained. Furthermore, suspended cells showed higher Rho activity than
      adherent cells in the presence of serum. These data indicate the existence of an
      adhesion-dependent negative-feedback loop. We also observed that both
      cytochalasin D and colchicine trigger Rho activation despite their opposite
      effects on stress fibers and focal adhesions. Our results show that ECM,
      cytoskeletal structures and soluble factors all contribute to regulation of Rho
      activity.

PMID- 9927418
TI  - Cytokinesis mediated through the recruitment of cortexillins into the cleavage
      furrow.
AB  - The fact that substrate-anchored Dictyostelium cells undergo cytokinesis in the
      absence of myosin II underscores the importance of other proteins in enabling the
      cleavage furrow to constrict. Cortexillins, a pair of actin-bundling proteins,
      are required for normal cleavage. They are targeted to the incipient furrow in
      wild-type and, more prominently, in myosin II-null cells. No other F-actin
      bundling or cross-linking protein tested is co-localized. Green fluorescent
      protein fusions show that the N-terminal actin-binding domain of cortexillin I is
      dispensable and the C-terminal region is sufficient for translocation to the
      furrow and the rescue of cytokinesis. Cortexillins are suggested to have a
      targeting signal for coupling to a myosin II-independent system that directs
      transport of membrane proteins to the cleavage furrow.

PMID- 9927419
TI  - Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand
      binding.
AB  - We recently reported the isolation and sequencing of sortilin, a new putative
      sorting receptor that binds receptor-associated protein (RAP). The luminal N
      terminus of sortilin comprises a consensus sequence for cleavage by furin,
      R41WRR44, which precedes a truncation originally found in sortilin isolated from
      human brain. We now show that the truncation results from cellular processing.
      Sortilin is synthesized as a proform which, in late Golgi compartments, is
      converted to the mature receptor by furin-mediated cleavage of a 44 residue N
      terminal propeptide. We further demonstrate that the propeptide exhibits pH
      dependent high affinity binding to fully processed sortilin, that the binding is
      competed for by RAP and the newly discovered sortilin ligand neurotensin, and
      that prevention of propeptide cleavage essentially prevents binding of RAP and
      neurotensin. The findings evidence that the propeptide sterically hinders ligands
      from gaining access to overlapping binding sites in prosortilin, and that
      cleavage and release of the propeptide preconditions sortilin for full functional
      activity. Although proteolytic processing is involved in the maturation of
      several receptors, the described exposure of previously concealed ligand-binding
      sites after furin-mediated cleavage of propeptide represents a novel mechanism in
      receptor activation.

PMID- 9927420
TI  - The Rap1 GTPase functions as a regulator of morphogenesis in vivo.
AB  - The Ras-related Rap GTPases are highly conserved across diverse species but their
      normal biological function is not well understood. Initial studies in mammalian
      cells suggested a role for Rap as a Ras antagonist. More recent experiments
      indicate functions in calcium- and cAMP-mediated signaling and it has been
      proposed that protein kinase A-mediated phosphorylation activates Rap in vivo. We
      show that Ras1-mediated signaling pathways in Drosophila are not influenced by
      Rap1 levels, suggesting that Ras1 and Rap1 function via distinct pathways.
      Moreover, a mutation that abolishes the putative cAMP-dependent kinase
      phosphorylation site of Drosophila Rap1 can still rescue the Rap1 mutant
      phenotype. Our experiments show that Rap1 is not needed for cell proliferation
      and cell-fate specification but demonstrate a critical function for Rap1 in
      regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1
      mutations also disrupt cell migrations and cause abnormalities in cell shape.
      These findings indicate a role for Rap proteins as regulators of morphogenesis in
      vivo.

PMID- 9927421
TI  - Biochemical and functional interactions between the neurotrophin receptors trk
      and p75NTR.
AB  - Neurotrophins bind to two structurally unrelated receptors, the trk tyrosine
      kinases and the neurotrophin receptor p75(NTR). Ligand activation of these two
      types of receptor can lead to opposite actions, in particular the prevention or
      activation of programmed cell death. Many cells co-express trk receptors and
      p75(NTR), and we found that p75(NTR) was co-precipitated with trkA, trkB and trkC
      in cells transfected with both receptor types. Co-precipitation of p75(NTR) was
      not observed with the epidermal growth factor receptor. Experiments with deletion
      constructs of trkB (the most abundant trk receptor in the brain) and p75(NTR)
      revealed that both the extracellular and intracellular domains of trkB and
      p75(NTR) contribute to the interaction. Blocking autophosphorylation of trkB
      substantially reduced the interactions between p75(NTR) and trkB constructs
      containing the intracellular, but not the extracellular, domains. We also found
      that co-expression of p75(NTR) with trkB resulted in a clear increase in the
      specificity of trkB activation by brain-derived neurotrophic factor, compared
      with neurotrophin-3 and neurotrophin-4/5. These results indicate a close
      proximity of the two neurotrophin receptors within cell membranes, and suggest
      that the signalling pathways they initiate may interact soon after their
      activation.

PMID- 9927422
TI  - Different functions for the thyroid hormone receptors TRalpha and TRbeta in the
      control of thyroid hormone production and post-natal development.
AB  - The biological activities of thyroid hormones are thought to be mediated by
      receptors generated by the TRalpha and TRbeta loci. The existence of several
      receptor isoforms suggests that different functions are mediated by specific
      isoforms and raises the possibility of functional redundancies. We have
      inactivated both TRalpha and TRbeta genes by homologous recombination in the
      mouse and compared the phenotypes of wild-type, and single and double mutant
      mice. We show by this method that the TRbeta receptors are the most potent
      regulators of the production of thyroid stimulating hormone (TSH). However, in
      the absence of TRbeta, the products of the TRalpha gene can fulfill this function
      as, in the absence of any receptors, TSH and thyroid hormone concentrations reach
      very high levels. We also show that TRbeta, in contrast to TRalpha, is
      dispensable for the normal development of bone and intestine. In bone, the
      disruption of both TRalpha and TRbeta genes does not modify the maturation delay
      observed in TRalpha -/- mice. In the ileum, the absence of any receptor results
      in a much more severe impairment than that observed in TRalpha -/- animals. We
      conclude that each of the two families of proteins mediate specific functions of
      triiodothyronin (T3), and that redundancy is only partial and concerns a limited
      number of functions.

PMID- 9927423
TI  - Bcl-xL regulates apoptosis by heterodimerization-dependent and -independent
      mechanisms.
AB  - A hydrophobic cleft formed by the BH1, BH2 and BH3 domains of Bcl-xL is
      responsible for interactions between Bcl-xL and BH3-containing death agonists.
      Mutants were constructed which did not bind to Bax but retained anti-apoptotic
      activity. Since Bcl-xL can form an ion channel in synthetic lipid membranes, the
      possibility that this property has a role in heterodimerization-independent cell
      survival was tested by replacing amino acids within the predicted channel-forming
      domain with the corresponding amino acids from Bax. The resulting chimera showed
      a reduced ability to adopt an open conductance state over a wide range of
      membrane potentials. Although this construct retained the ability to
      heterodimerize with Bax and to inhibit apoptosis, when a mutation was introduced
      that rendered the chimera incapable of heterodimerization, the resulting protein
      failed to prevent both apoptosis in mammalian cells and Bax-mediated growth
      defect in yeast. Similar to mammalian cells undergoing apoptosis, yeast cells
      expressing Bax exhibited changes in mitochondrial properties that were inhibited
      by Bcl-xL through heterodimerization-dependent and -independent mechanisms. These
      data suggest that Bcl-xL regulates cell survival by at least two distinct
      mechanisms; one is associated with heterodimerization and the other with the
      ability to form a sustained ion channel.

PMID- 9927424
TI  - Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin
      cdk6 complex.
AB  - The Kaposi's sarcoma-associated human herpesvirus 8 (KSHV/HHV8) encodes a protein
      similar to cellular cyclins. This cyclin is most closely related to cellular D
      type cyclins, but biochemically it behaves atypically in various respects.
      Complexes formed between the viral cyclin and the cyclin-dependent kinase
      subunit, cdk6, can phosphorylate a wider range of substrates and are resistant to
      cdk inhibitory proteins. We show here that the KSHV-cyclin-cdk6 complex
      phosphorylates p27(Kip) on a C-terminal threonine that is implicated in
      destabilization of this cdk inhibitor. Expression of the viral cyclin in tissue
      culture cells overcomes a cell cycle block by p27(Kip). However, full cell-cycle
      transit of these cells appears to depend on C-terminal phosphorylation of
      p27(Kip) and seems to involve transactivation of other cellular cyclin-dependent
      kinases. A p27(Kip)-phosphorylating cdk6 complex exists in cell lines derived
      from primary effusion lymphoma and in Kaposi's sarcoma, this indicating that
      virally induced p27(Kip) degradation may occur in KSHV-associated tumours.

PMID- 9927425
TI  - Modulation of p27(Kip1) levels by the cyclin encoded by Kaposi's sarcoma
      associated herpesvirus.
AB  - DNA tumour viruses have evolved a number of mechanisms by which they deregulate
      normal cellular growth control. We have recently described the properties of a
      cyclin encoded by human herpesvirus 8 (also known as Kaposi's sarcoma-associated
      herpesvirus) which is able to resist the actions of p16(Ink4a), p21(Cip1) and
      p27(Kip1) cdk inhibitors. Here we investigate the mechanism involved in the
      subversion of a G1 blockade imposed by overexpression of p27(Kip1). We
      demonstrate that binding of K cyclin to cdk6 expands the substrate repertoire of
      this cdk to include a number of substrates phosphorylated by cyclin-cdk2
      complexes but not cyclin D1-cdk6. Included amongst these substrates is p27(Kip1)
      which is phosphorylated on Thr187. Expression of K cyclin in mammalian cells
      leads to p27(Kip1) downregulation, this being consistent with previous studies
      indicating that phosphorylation of p27(Kip1) on Thr187 triggers its
      downregulation. K cyclin expression is not able to prevent a G1 arrest imposed by
      p27(Kip1) in which Thr187 is mutated to non-phosphorylatable Ala. These results
      imply that K cyclin is able to bypass a p27(Kip1)-imposed G1 arrest by
      facilitating phosphorylation and downregulation of p27(Kip1) to enable activation
      of endogenous cyclin-cdk2 complexes. The extension of the substrate repertoire of
      cdk6 by K cyclin is likely to contribute to the deregulation of cellular growth
      by this herpesvirus-encoded cyclin.

PMID- 9927426
TI  - Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for
      growth factor-induced gene expression and cell cycle entry.
AB  - Mitogen-activated protein kinase (MAPK) modules, composed of three protein
      kinases activated by successive phosphorylation, are involved in the signal
      transduction of a wide range of extracellular agents. In mammalian cells,
      mitogenic stimulation triggers the translocation of p42/p44MAPK from the
      cytoplasm to the nucleus, whereas the other protein kinases of the module remain
      cytosolic. Since MAPK has been shown to phosphorylate and activate nuclear
      targets, such as the transcription factor Elk1, it has been proposed, but not yet
      demonstrated, that MAPK nuclear translocation could represent a critical step in
      signal transduction. In this study, we sequestered p42/p44MAPK in the cytoplasm
      by the expression of a catalytically inactive form of cytoplasmic MAP kinase
      phosphatase (MKP-3/Pyst-1). Sequestering MAPK in the cytoplasm did not alter its
      activation or its ability to phosphorylate cytoplasmic substrates of MAPK
      (p90RSK1 or an engineered cytoplasmic form of Elk1). In contrast, prevention of
      MAPK nuclear translocation strongly inhibited Elk1-dependent gene transcription
      and the ability of cells to reinitiate DNA replication in response to growth
      factors. Thus the relocalization of MAPK to the nucleus appears to be an
      important regulatory step for mitogen-induced gene expression and cell cycle re
      entry.

PMID- 9927427
TI  - TIMELESS-dependent positive and negative autoregulation in the Drosophila
      circadian clock.
AB  - The timeless protein (TIM) is a central component of the circadian pacemaker
      machinery of the fruitfly Drosophila melanogaster. Both TIM and its partner
      protein, the period protein PER, show robust circadian oscillations in mRNA and
      protein levels. Yet the role of TIM in the rhythm generation mechanism is largely
      unknown. To analyze TIM function, we constructed transgenic flies that carry a
      heat shock-inducible copy of the timeless gene (tim) in an arrhythmic tim loss-of
      function genetic background. When heat shocked, TIM levels in these flies rapidly
      increased and initiated a molecular cycle of PER accumulation and processing with
      dynamics very similar to the PER cycle observed in wild-type flies. Analysis of
      period (per) mRNA levels and transcription uncovered a novel role for TIM in
      clock regulation: TIM increases per mRNA levels through a post-transcriptional
      mechanism. Our results suggest positive as well as negative autoregulation in the
      Drosophila circadian clock.

PMID- 9927428
TI  - Regulation of embryonic/fetal globin genes by nuclear hormone receptors: a novel
      perspective on hemoglobin switching.
AB  - The CCAAT box is one of the conserved motifs found in globin promoters. It binds
      the CP1 protein. We noticed that the CCAAT-box region of embryonic/fetal, but not
      adult, globin promoters also contains one or two direct repeats of a short motif
      analogous to DR-1 binding sites for non-steroid nuclear hormone receptors. We
      show that a complex previously named NF-E3 binds to these repeats. In transgenic
      mice, destruction of the CCAAT motif within the human epsilon-globin promoter
      leads to substantial reduction in epsilon expression in embryonic erythroid
      cells, indicating that CP1 activates epsilon expression; in contrast, destruction
      of the DR-1 elements yields striking epsilon expression in definitive
      erythropoiesis, indicating that the NF-E3 complex acts as a developmental
      repressor of the epsilon gene. We also show that NF-E3 is immunologically related
      to COUP-TF orphan nuclear receptors. One of these, COUP-TF II, is expressed in
      embryonic/fetal erythroid cell lines, murine yolk sac, intra-embryonic
      splanchnopleura and fetal liver. In addition, the structure and abundance of NF
      E3/COUP-TF complexes vary during fetal liver development. These results elucidate
      the structure as well as the role of NF-E3 in globin gene expression and provide
      evidence that nuclear hormone receptors are involved in the control of globin
      gene switching.

PMID- 9927429
TI  - Co-operative DNA binding by GAGA transcription factor requires the conserved
      BTB/POZ domain and reorganizes promoter topology.
AB  - The POZ domain is a conserved protein-protein interaction motif present in a
      variety of transcription factors involved in development, chromatin remodelling
      and human cancers. Here, we study the role of the POZ domain of the GAGA
      transcription factor in promoter recognition. Natural target promoters for GAGA
      typically contain multiple GAGA-binding elements. Our results show that the POZ
      domain mediates strong co-operative binding to multiple sites but inhibits
      binding to single sites. Protein cross-linking and gel filtration chromatography
      experiments established that the POZ domain is required for GAGA oligomerization
      into higher order complexes. Thus, GAGA oligomerization increases binding
      specificity by selecting only promoters with multiple sites. Electron microscopy
      revealed that GAGA binds to multiple sites as a large oligomer and induces
      bending of the promoter DNA. Our results indicate a novel mode of DNA binding by
      GAGA, in which a large GAGA complex binds multiple GAGA elements that are spread
      out over a region of a few hundred base pairs. We suggest a model in which the
      promoter DNA is wrapped around a GAGA multimer in a conformation that may exclude
      normal nucleosome formation.

PMID- 9927430
TI  - A mutation in region 1.1 of sigma70 affects promoter DNA binding by Escherichia
      coli RNA polymerase holoenzyme.
AB  - The sigma subunit of eubacterial RNA polymerase is essential for initiation of
      transcription at promoter sites. It directs recognition of DNA sequences by
      holoenzyme (alpha2betabeta'sigma) and facilitates subsequent steps in the
      initiation pathway. The primary sigma factor from Escherichia coli, sigma70, has
      four regions that are conserved among members of the sigma70 family. Previous
      work has shown that region 1.1 modulates DNA binding by regions 2 and 4 when
      sigma is separated from the core subunits, and is required for efficient
      progression through the later steps of initiation in the context of holoenzyme.
      In this report, we show that an amino acid substitution at position 53 in region
      1.1, which converts isoleucine to alanine (I53A), creates a sigma factor that
      associates with the core subunits to form holoenzyme, but the holoenzyme is
      severely deficient for promoter binding. The I53A phenotype can be suppressed by
      truncation of five amino acids from the C-terminus of sigma70. We propose that
      the behavior of sigma70-I53A is a consequence of impaired ability to undergo a
      critical conformational change upon binding to the core subunits, which is needed
      to expose the DNA-binding domains and confer promoter recognition capability upon
      holoenzyme.

PMID- 9927431
TI  - Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and
      transforming mutations stabilize Myc.
AB  - The human proto-oncogene c-myc encodes a highly unstable transcription factor
      that promotes cell proliferation. Although the extreme instability of Myc plays
      an important role in preventing its accumulation in normal cells, little is known
      about how Myc is targeted for rapid destruction. Here, we have investigated
      mechanisms regulating the stability of Myc. We show that Myc is destroyed by
      ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely
      regulate its stability: a transcriptional activation domain that promotes Myc
      destruction, and a region required for association with the POZ domain protein
      Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer
      associated and transforming mutations within its transcriptional activation
      domain. Our data reveal a complex network of interactions regulating Myc
      destruction, and imply that enhanced protein stability contributes to oncogenic
      transformation by mutant Myc proteins.

PMID- 9927432
TI  - Indirect regulation of translational termination efficiency at highly expressed
      genes and recoding sites by the factor recycling function of Escherichia coli
      release factor RF3.
AB  - Prokaryotic release factor RF3 is a stimulatory protein that increases the rate
      of translational termination by the decoding release factors RF1 and RF2. The
      favoured model for RF3 function is the recycling of RF1 and RF2 after polypeptide
      release by displacing the factors from the ribosome. In this study, we have
      demonstrated that RF3 also plays an indirect role in the decoding of stop signals
      of highly expressed genes and recoding sites by accentuating the influence of the
      base following the stop codon (+4 base) on termination signal strength. The
      efficiency of decoding strong stop signals (e.g. UAAU and UAAG) in vivo is
      markedly improved with increased RF3 activity, while weak signals (UGAC and UAGC)
      are only modestly affected. However, RF3 is not responsible for the +4 base
      influence on termination signal strength, since prfC- strains lacking the protein
      still exhibit the same qualitative effect. The differential effect of RF3 at stop
      signals can be mimicked by modest overexpression of decoding RF. These findings
      can be interpreted according to current views of RF3 as a recycling factor, which
      functions to maintain the concentration of free decoding RF at stop signals, some
      of which are highly responsive to changes in RF levels.

PMID- 9927433
TI  - Interactions of ribosome nascent chain complexes of the chloroplast-encoded D1
      thylakoid membrane protein with cpSRP54.
AB  - The mechanisms of targeting, insertion and assembly of the chloroplast-encoded
      thylakoid membrane proteins are unknown. In this study, we investigated these
      mechanisms for the chloroplast-encoded polytopic D1 thylakoid membrane protein,
      using a homologous translation system isolated from tobacco chloroplasts.
      Truncated forms of the psbA gene were translated and stable ribosome nascent
      chain complexes were purified. To probe the interactions with the soluble
      components of the targeting machinery, we used UV-activatable cross-linkers
      incorporated at specific positions in the nascent chains, as well as conventional
      sulfhydryl cross-linkers. With both cross-linking approaches, the D1 ribosome
      nascent chain was photocross-linked to cpSRP54. cpSRP54 was shown to interact
      only when the D1 nascent chain was still attached to the ribosome. The
      interaction was strongly dependent on the length of the nascent chain that
      emerged from the ribosome, as well as the cross-link position. No interactions
      with soluble SecA or cpSRP43 were found. These results imply a role for cpSRP54
      in D1 biogenesis.

PMID- 9927434
TI  - Retention of empty MHC class I molecules by tapasin is essential to reconstitute
      antigen presentation in invertebrate cells.
AB  - Presentation of antigen-derived peptides by major histocompatibility complex
      (MHC) class I molecules is dependent on an endoplasmic reticulum (ER) resident
      glycoprotein, tapasin, which mediates their interaction with the transporter
      associated with antigen processing (TAP). Independently of TAP, tapasin was
      required for the presentation of peptides targeted to the ER by signal sequences
      in MHC class I-transfected insect cells. Tapasin increased MHC class I peptide
      loading by retaining empty but not peptide-containing MHC class I molecules in
      the ER. Upon co-expression of TAP, this retention/release function of tapasin was
      sufficient to reconstitute MHC class I antigen presentation in insect cells, thus
      defining the minimal non-housekeeping functions required for MHC class I antigen
      presentation.

PMID- 9927435
TI  - Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co
      chaperones.
AB  - The in vivo function of the heat shock protein 90 (Hsp90) molecular chaperone is
      dependent on the binding and hydrolysis of ATP, and on interactions with a
      variety of co-chaperones containing tetratricopeptide repeat (TPR) domains. We
      have now analysed the interaction of the yeast TPR-domain co-chaperones Sti1 and
      Cpr6 with yeast Hsp90 by isothermal titration calorimetry, circular dichroism
      spectroscopy and analytical ultracentrifugation, and determined the effect of
      their binding on the inherent ATPase activity of Hsp90. Sti1 and Cpr6 both bind
      with sub-micromolar affinity, with Sti1 binding accompanied by a large
      conformational change. Two co-chaperone molecules bind per Hsp90 dimer, and Sti1
      itself is found to be a dimer in free solution. The inherent ATPase activity of
      Hsp90 is completely inhibited by binding of Sti1, but is not affected by Cpr6,
      although Cpr6 can reactivate the ATPase activity by displacing Sti1 from Hsp90.
      Bound Sti1 makes direct contact with, and blocks access to the ATP-binding site
      in the N-terminal domain of Hsp90. These results reveal an important role for TPR
      domain co-chaperones as regulators of the ATPase activity of Hsp90, showing that
      the ATP-dependent step in Hsp90-mediated protein folding occurs after the binding
      of the folding client protein, and suggesting that ATP hydrolysis triggers client
      protein release.

PMID- 9927436
TI  - p53 DNA binding can be modulated by factors that alter the conformational
      equilibrium.
AB  - The p53 tumor suppressor protein is a dimer of dimers that binds its consensus
      DNA sequence (containing two half-sites) as a pair of clamps. We show here that
      after one wild-type dimer of a tetramer binds to a half-site on the DNA, the
      other (unbound) dimer can be in either the wild-type or the mutant conformation.
      An equilibrium state between these two conformations exists and can be modulated
      by two types of regulators. One type modifies p53 biochemically and determines
      the intrinsic balance of the equilibrium. The other type of regulator binds
      directly to one or both dimers in a p53 tetramer, trapping each dimer in one or
      the other conformation. In the wild-type conformation, the second dimer can bind
      to the second DNA half-site, resulting in drastically enhanced stability of the
      p53-DNA complex. Importantly, a genotypically mutant p53 can also be in
      equilibrium with the wild-type conformation, and when trapped in this
      conformation can bind DNA.

PMID- 9927437
TI  - The internal workings of a DNA polymerase clamp-loading machine.
AB  - Replicative DNA polymerases are multiprotein machines that are tethered to DNA
      during chain extension by sliding clamp proteins. The clamps are designed to
      encircle DNA completely, and they are manipulated rapidly onto DNA by the ATP
      dependent activity of a clamp loader. We outline the detailed mechanism of gamma
      complex, a five-protein clamp loader that is part of the Escherichia coli
      replicase, DNA polymerase III holoenzyme. The gamma complex uses ATP to open the
      beta clamp and assemble it onto DNA. Surprisingly, ATP is not needed for gamma
      complex to crack open the beta clamp. The function of ATP is to regulate the
      activity of one subunit, delta, which opens the clamp simply by binding to it.
      The delta' subunit acts as a modulator of the interaction between delta and beta.
      On binding ATP, the gamma complex is activated such that the delta' subunit
      permits delta to bind beta and crack open the ring at one interface. The clamp
      loader-open clamp protein complex is now ready for an encounter with primed DNA
      to complete assembly of the clamp around DNA. Interaction with DNA stimulates ATP
      hydrolysis which ejects the gamma complex from DNA, leaving the ring to close
      around the duplex.

PMID- 9927438
TI  - Wild-type Flp recombinase cleaves DNA in trans.
AB  - Site-specific recombinases of the Integrase family utilize a common chemical
      mechanism to break DNA strands during recombination. A conserved Arg-His-Arg
      triad activates the scissile phosphodiester bond, and an active-site tyrosine
      provides the nucleophile to effect DNA cleavage. Is the tyrosine residue for the
      cleavage event derived from the same recombinase monomer which provides the RHR
      triad (DNA cleavage in cis), or are the triad and tyrosine derived from two
      separate monomers (cleavage in trans)? Do all members of the family follow the
      same cleavage rule, cis or trans? Solution studies and available structural data
      have provided conflicting answers. Experimental results with the Flp recombinase
      which strongly support trans cleavage have been derived either by pairing two
      catalytic mutants of Flp or by pairing wild-type Flp and a catalytic mutant. The
      inclusion of the mutant has raised new concerns, especially because of the
      apparent contradictions in their cleavage modes posed by other Int family
      members. Here we test the cleavage mode of Flp using an experimental design which
      excludes the use of the mutant protein, and show that the outcome is still only
      trans DNA cleavage.

PMID- 9927439
TI  - The ascendency of developmental genetics, or how the T complex educated a
      generation of developmental biologists.

PMID- 9927440
TI  - Population dynamics of HIV-1 inferred from gene sequences.
AB  - A method for the estimation of population dynamic history from sequence data is
      described and used to investigate the past population dynamics of HIV-1 subtypes
      A and B. Using both gag and env gene alignments the effective population size of
      each subtype is estimated and found to be surprisingly small. This may be a
      result of the selective sweep of mutations through the population, or may
      indicate an important role of genetic drift in the fixation of mutations. The
      implications of these results for the spread of drug-resistant mutations and
      transmission dynamics, and also the roles of selection and recombination in
      shaping HIV-1 genetic diversity, are discussed. A larger estimated effective
      population size for subtype A may be the result of differences in time of origin,
      transmission dynamics, and/or population structure. To investigate the importance
      of population structure a model of population subdivision was fitted to each
      subtype, although the improvement in likelihood was found to be nonsignificant.

PMID- 9927441
TI  - Escherichia coli mutM suppresses illegitimate recombination induced by oxidative
      stress.
AB  - DNA damage by oxidative stress is one of the causes of mutagenesis. However,
      whether or not DNA damage induces illegitimate recombination has not been
      determined. To study the effect of oxidative stress on illegitimate
      recombination, we examined the frequency of lambdabio transducing phage in the
      presence of hydrogen peroxide and found that this reagent enhances illegitimate
      recombination. To clarify the types of illegitimate recombination, we examined
      the effect of mutations in mutM and related genes on the process. The frequency
      of lambdabio transducing phage was 5- to 12-fold higher in the mutM mutant than
      in the wild type, while the frequency in the mutY and mutT mutants was comparable
      to that of the wild type. Because 7,8-dihydro-8-oxoguanine (8-oxoG) and formamido
      pyrimidine (Fapy) lesions can be removed from DNA by MutM protein, these lesions
      are thought to induce illegitimate recombination. Analysis of recombination
      junctions showed that the recombination at Hotspot I accounts for 22 or 4% of
      total lambdabio transducing phages in the wild type or in the mutM mutant,
      respectively. The preferential increase of recombination at nonhotspot sites with
      hydrogen peroxide in the mutM mutant was discussed on the basis of a new model,
      in which 8-oxoG and/or Fapy residues may introduce double-strand breaks into DNA.

PMID- 9927442
TI  - An allele of RFA1 suppresses RAD52-dependent double-strand break repair in
      Saccharomyces cerevisiae.
AB  - An allele of RFA1, the largest subunit of the single-stranded DNA-binding complex
      RP-A, was identified as a suppressor of decreased direct-repeat recombination in
      rad1 rad52 double mutants. In this study, we used two LEU2 direct-repeat assays
      to investigate the mechanism by which the rfa1-D228Y allele increases
      recombination. We found that both intrachromatid and sister chromatid
      recombination are stimulated in rfa1-D228Y strains. In a rad1 rad52 background,
      however, the majority of the increased recombination is caused by stimulation of
      deletion events by an intrachromatid recombination mechanism that is likely to be
      single-strand annealing. Studies in which an HO endonuclease cut was introduced
      between the two leu2 copies indicate that the rfa1-D228Y mutation partially
      suppresses the rad52 defect in recovering recombination products. Furthermore,
      molecular analysis of processing and product formation kinetics reveals that, in
      a rad52 background, the rfa1-D228Y mutation results in increased levels of
      recombinant products and the disappearance of large single-stranded intermediates
      characteristic of rad52 strains. On the basis of these results, we propose that
      in the absence of wild-type Rad52, the interaction of RP-A with single-stranded
      DNA inhibits strand annealing, and that this inhibition is overcome by the rfa1
      D228Y mutation.

PMID- 9927443
TI  - Interaction between the MEC1-dependent DNA synthesis checkpoint and G1 cyclin
      function in Saccharomyces cerevisiae.
AB  - The completion of DNA synthesis in yeast is monitored by a checkpoint that
      requires MEC1 and RAD53. Here we show that deletion of the Saccharomyces
      cerevisiae G1 cyclins CLN1 and CLN2 suppressed the essential requirement for MEC1
      function. Wild-type levels of CLN1 and CLN2, or overexpression of CLN1, CLN2, or
      CLB5, but not CLN3, killed mec1 strains. We identified RNR1, which encodes a
      subunit of ribonucleotide reductase, as a high-copy suppressor of the lethality
      of mec1 GAL1-CLN1. Northern analysis demonstrated that RNR1 expression is reduced
      by CLN1 or CLN2 overexpression. Because limiting RNR1 expression would be
      expected to decrease dNTP pools, CLN1 and CLN2 may cause lethality in mec1
      strains by causing initiation of DNA replication with inadequate dNTPs. In
      contrast to mec1 mutants, MEC1 strains with low dNTPs would be able to delay S
      phase and thereby remain viable. We propose that the essential function for MEC1
      may be the same as its checkpoint function during hydroxyurea treatment, namely,
      to slow S phase when nucleotides are limiting. In a cln1 cln2 background, a
      prolonged period of expression of genes turned on at the G1-S border, such as
      RNR1, has been observed. Thus deletion of CLN1 and CLN2 could function similarly
      to overexpression of RNR1 in suppressing mec1 lethality.

PMID- 9927444
TI  - MGA2 or SPT23 is required for transcription of the delta9 fatty acid desaturase
      gene, OLE1, and nuclear membrane integrity in Saccharomyces cerevisiae.
AB  - MGA2 and SPT23 are functionally and genetically redundant homologs in
      Saccharomyces cerevisiae. Both genes are implicated in the transcription of a
      subset of genes, including Ty retrotransposons and Ty-induced mutations. Neither
      gene is essential for growth, but mga2 spt23 double mutants are inviable. We have
      isolated a gene-specific activator, SWI5, and the Delta9 fatty acid desaturase of
      yeast, OLE1, as multicopy suppressors of an mga2Delta spt23 temperature-sensitive
      mutation (spt23-ts). The level of unsaturated fatty acids decreases 35-40% when
      the mga2Delta spt23-ts mutant is incubated at 37 degrees. Electron microscopy of
      these cells reveals a separation of inner and outer nuclear membranes that is
      sometimes accompanied by vesicle-like projections in the intermembrane space. The
      products of Ole1p catalysis, oleic acid and palmitoleic acid, suppress mga2Delta
      spt23-ts and mga2Delta spt23Delta lethality and restore normal nuclear membrane
      morphology. Furthermore, the level of the OLE1 transcript decreases more than 15
      fold in the absence of wild-type Mga2p and Spt23p. Our results suggest that
      Mga2p/Spt23p control cell viability by stimulating OLE1 transcription.

PMID- 9927445
TI  - Role of Saccharomyces cerevisiae chromatin assembly factor-I in repair of
      ultraviolet radiation damage in vivo.
AB  - In vitro, the protein complex Chromatin Assembly Factor-I (CAF-I) from human or
      yeast cells deposits histones onto DNA templates after replication. In
      Saccharomyces cerevisiae, the CAC1, CAC2, and CAC3 genes encode the three CAF-I
      subunits. Deletion of any of the three CAC genes reduces telomeric gene silencing
      and confers an increase in sensitivity to killing by ultraviolet (UV) radiation.
      We used double and triple mutants involving cac1Delta and yeast repair gene
      mutations to show that deletion of the CAC1 gene increases the UV sensitivity of
      cells mutant in genes from each of the known DNA repair epistasis groups. For
      example, double mutants involving cac1Delta and excision repair gene deletions
      rad1Delta or rad14Delta showed increased UV sensitivity, as did double mutants
      involving cac1Delta and deletions of members of the RAD51 recombinational repair
      group. cac1Delta also increased the UV sensitivity of strains with defects in
      either the error-prone (rev3Delta) or error-free (pol30-46) branches of RAD6
      mediated postreplicative DNA repair but did not substantially increase the
      sensitivity of strains carrying null mutations in the RAD6 or RAD18 genes.
      Deletion of CAC1 also increased the UV sensitivity and rate of UV-induced
      mutagenesis in rad5Delta mutants, as has been observed for mutants defective in
      error-free postreplicative repair. Together, these data suggest that CAF-I has a
      role in error-free postreplicative damage repair and may also have an auxiliary
      role in other repair mechanisms. Like the CAC genes, RAD6 is also required for
      gene silencing at telomeres. We find an increased loss of telomeric gene
      silencing in rad6Delta cac1Delta and rad18Delta cac1Delta double mutants,
      suggesting that CAF-I and multiple factors in the postreplicative repair pathway
      influence chromosome structure.

PMID- 9927447
TI  - A mutation of the yeast gene encoding PCNA destabilizes both microsatellite and
      minisatellite DNA sequences.
AB  - The POL30 gene of the yeast Saccharomyces cerevisiae encodes the proliferating
      cell nuclear antigen (PCNA), a protein required for processive DNA synthesis by
      DNA polymerase delta and epsilon. We examined the effects of the pol30-52
      mutation on the stability of microsatellite (1- to 8-bp repeat units) and
      minisatellite (20-bp repeat units) DNA sequences. It had previously been shown
      that this mutation destabilizes dinucleotide repeats 150-fold and that this
      effect is primarily due to defects in DNA mismatch repair. From our analysis of
      the effects of pol30-52 on classes of repetitive DNA with longer repeat unit
      lengths, we conclude that this mutation may also elevate the rate of DNA
      polymerase slippage. The effect of pol30-52 on tracts of repetitive DNA with
      large repeat unit lengths was similar, but not identical, to that observed
      previously for pol3-t, a temperature-sensitive mutation affecting DNA polymerase
      delta. Strains with both pol30-52 and pol3-t mutations grew extremely slowly and
      had minisatellite mutation rates considerably greater than those observed in
      either single mutant strain.

PMID- 9927446
TI  - Characterization of the repeat-tract instability and mutator phenotypes conferred
      by a Tn3 insertion in RFC1, the large subunit of the yeast clamp loader.
AB  - The RFC1 gene encodes the large subunit of the yeast clamp loader (RFC) that is a
      component of eukaryotic DNA polymerase holoenzymes. We identified a mutant allele
      of RFC1 (rfc1::Tn3) from a large collection of Saccharomyces cerevisiae mutants
      that were inviable when present in a rad52 null mutation background. Analysis of
      rfc1::Tn3 strains indicated that they displayed both a mutator and repeat-tract
      instability phenotype. Strains bearing this allele were characterized in
      combination with mismatch repair (msh2Delta, pms1Delta), double-strand break
      repair (rad52), and DNA replication (pol3-01, pol30-52, rth1Delta/rad27Delta)
      mutations in both forward mutation and repeat-tract instability assays. This
      analysis indicated that the rfc1::Tn3 allele displays synthetic lethality with
      pol30, pol3, and rad27 mutations. Measurement of forward mutation frequencies in
      msh2Delta rfc1:Tn3 and pms1Delta rfc1:Tn3 strains indicated that the rfc1::Tn3
      mutant displayed a mutation frequency that appeared nearly multiplicative with
      the mutation frequency exhibited by mismatch-repair mutants. In repeat-tract
      instability assays, however, the rfc1::Tn3 mutant displayed a tract instability
      phenotype that appeared epistatic to the phenotype displayed by mismatch-repair
      mutants. From these data we propose that defects in clamp loader function result
      in DNA replication errors, a subset of which are acted upon by the mismatch
      repair system.

PMID- 9927448
TI  - HMR-I is an origin of replication and a silencer in Saccharomyces cerevisiae.
AB  - There appear to be fundamental differences between the properties of the
      silencers at HML and HMR, with some being origins of replication and others not.
      Moreover, past studies have suggested that HMR-I's role in silencing may be
      restricted to plasmid contexts. This study established that HMR-I, like HMR-E and
      unlike either HML silencer, is an origin of replication. Moreover, both HMR-E and
      HMR-I contribute to silencing of a chromosomal HMR locus. In addition, we found
      that Abf1p plays no unique role in silencer function.

PMID- 9927449
TI  - POG1, a novel yeast gene, promotes recovery from pheromone arrest via the G1
      cyclin CLN2.
AB  - In the absence of a successful mating, pheromone-arrested Saccharomyces
      cerevisiae cells reenter the mitotic cycle through a recovery process that
      involves downregulation of the mating mitogen-activated protein kinase (MAPK)
      cascade. We have isolated a novel gene, POG1, whose promotion of recovery
      parallels that of the MAPK phosphatase Msg5. POG1 confers alpha-factor resistance
      when overexpressed and enhances alpha-factor sensitivity when deleted in the
      background of an msg5 mutant. Overexpression of POG1 inhibits alpha-factor
      induced G1 arrest and transcriptional repression of the CLN1 and CLN2 genes. The
      block in transcriptional repression occurs at SCB/MCB promoter elements by a
      mechanism that requires Bck1 but not Cln3. Genetic tests strongly argue that POG1
      promotes recovery through upregulation of the CLN2 gene and that the resulting
      Cln2 protein promotes recovery primarily through an effect on Ste20, an activator
      of the mating MAPK cascade. A pog1 cln3 double mutant displays synthetic mutant
      phenotypes shared by cell-wall integrity and actin cytoskeleton mutants, with no
      synthetic defect in the expression of CLN1 or CLN2. These and other results
      suggest that POG1 may regulate additional genes during vegetative growth and
      recovery.

PMID- 9927451
TI  - Aspergillus nidulans swo mutants show defects in polarity establishment, polarity
      maintenance and hyphal morphogenesis.
AB  - When the spores of filamentous fungi break dormancy, they grow isotropically,
      adding cell wall material uniformly in every direction. Later they switch to
      polarized growth, with new material added to the tip of an emerging germ tube. To
      identify genes involved in the synthesis and localization of cell wall material
      in filamentous fungi, we screened a collection of temperature-sensitive
      Aspergillus nidulans mutants for swollen cells. We have isolated mutants
      representing eight genes involved in polarity establishment, polarity
      maintenance, and hyphal morphogenesis. On the basis of the results of temperature
      shift experiments, swo C, D, and F are required to establish polarity, while swoA
      is required to maintain polarity. swo B, E, G, and H are involved in later hyphal
      morphogenesis. Our results suggest that polarity establishment and polarity
      maintenance are genetically separate events and that a persistent signal is
      required for apical extension in A. nidulans.

PMID- 9927450
TI  - Molecular characterization of tol, a mediator of mating-type-associated
      vegetative incompatibility in Neurospora crassa.
AB  - The mating-type locus in the haploid filamentous fungus, Neurospora crassa,
      controls mating and sexual development. The fusion of reproductive structures of
      opposite mating type, A and a, is required to initiate sexual reproduction.
      However, the fusion of hyphae of opposite mating type during vegetative growth
      results in growth inhibition and cell death, a process that is mediated by the
      tol locus. Mutations in tol are recessive and suppress mating-type-associated
      heterokaryon incompatibility. In this study, we describe the cloning and
      characterization of tol. The tol gene encodes a putative 1011-amino-acid
      polypeptide with a coiled-coil domain and a leucine-rich repeat. Both regions are
      required for tol activity. Repeat-induced point mutations in tol result in
      mutants that are wild type during vegetative growth and sexual reproduction, but
      that allow opposite mating-type individuals to form a vigorous heterokaryon.
      Transcript analyses show that tol mRNA is present during vegetative growth but
      absent during a cross. These data suggest that tol transcription is repressed to
      allow the coexistence of opposite mating-type nuclei during the sexual
      reproductive phase. tol is expressed in a mat A, mat a, A/a partial diploid and
      in a mating-type deletion strain, indicating that MAT A-1 and MAT a-1 are not
      absolutely required for transcription or repression of tol. These data suggest
      that TOL may rather interact with MAT A-1 and/or MAT a-1 (or downstream products)
      to form a death-triggering complex.

PMID- 9927453
TI  - The translocation-associated tox1 locus of Cochliobolus heterostrophus is two
      genetic elements on two different chromosomes.
AB  - Previously, Tox1 was defined as a single genetic element controlling the
      difference between races of Cochliobolus heterostrophus: race T is highly
      virulent on T-cytoplasm corn and produces the polyketide T-toxin; race O is
      weakly virulent and does not produce T-toxin. Here we report that Tox1 is two
      loci, Tox1A and Tox1B, on two different chromosomes. Evidence for two loci
      derives from: (1) the appearance of 25% Tox+ progeny in crosses between induced
      Tox1(-) mutants, one defective at Tox1A, the other at Tox1B; (2) the ability of
      Tox1A- + Tox1B- heterokaryons to complement for T-toxin production; and (3)
      electrophoretic karyotypes proving that Tox1(-) mutations are physically located
      on two different chromosomes. Data showing Tox1 as a single genetic element are
      reconciled with those proving it is two loci by the fact that Tox1 is inseparably
      linked to the breakpoints of a reciprocal translocation; the translocation
      results in a four-armed linkage group. In crosses where the translocation is
      heterozygous (i.e., race T by race O), all markers linked to the four-armed
      intersection appear linked to each other; in crosses between induced Tox1(-)
      mutants, complications due to the translocation are eliminated and the two loci
      segregate independently.

PMID- 9927452
TI  - Extracellular complementation and the identification of additional genes involved
      in aerial mycelium formation in Streptomyces coelicolor.
AB  - Morphogenesis in the bacterium Streptomyces coelicolor involves the formation of
      a lawn of hair-like aerial hyphae on the colony surface that stands up in the air
      and differentiates into chains of spores. bld mutants are defective in the
      formation of this aerial mycelium and grow as smooth, hairless colonies. When
      certain pairs of bld mutants are grown close to one another on rich sporulation
      medium, they exhibit extracellular complementation such that one mutant restores
      aerial mycelium formation to the other. The extracellular complementation
      relationships of most of the previously isolated bld mutants placed them in a
      hierarchy of extracellular complementation groups. We have screened for further
      bld mutants with precautions intended to maximize the discovery of additional
      genes. Most of the 50 newly isolated mutant strains occupy one of three of the
      previously described positions in the hierarchy, behaving like bldK, bldC, or
      bldD mutants. We show that the mutations in some of the strains that behave like
      bldK are bldK alleles but that others fall in a cluster at a position on the
      chromosome distinct from that of any known bld gene. We name this locus bldL. By
      introducing cloned genes into the strains that exhibit bldC or bldD-like
      extracellular complementation phenotypes, we show that most of these strains are
      likely to contain mutations in genes other than bldC or bldD. These results
      indicate that the genetic control of aerial mycelium formation is more complex
      than previously recognized and support the idea that a high proportion of bld
      genes are directly or indirectly involved in the production of substances that
      are exchanged between cells during morphological differentiation.

PMID- 9927454
TI  - A mutation in the flanking 5'-TA-3' dinucleotide prevents excision of an internal
      eliminated sequence from the Paramecium tetraurelia genome.
AB  - The germline chromosomes in Paramecium and other ciliated protozoa contain
      regions of DNA that are excised and eliminated during the development of a new
      macronuclear genome. Paramecium tetraurelia internal eliminated sequences (IESs)
      are invariably flanked by a 5'-TA-3' dinucleotide sequence that is part of a
      larger 8-bp terminal inverted-repeat consensus sequence. Both features, the
      absolutely conserved 5'-TA-3' and the remaining 6-bp terminal inverted repeat,
      are shared with the mariner/Tc1 class of transposons. In this article we describe
      a mutant cell line (AIM-2) defective in excision of a single IES from the coding
      region of the A51 surface antigen gene. Excision of the 370-bp IES6649 is
      prevented by a single A to G transition in the invariably conserved 5'-TA-3'
      dinucleotide. Failure to excise IES6649 also revealed a 29-bp IES located inside
      IES6649. Additional experiments with the previously isolated AIM-1 mutant, which
      also contains an internal IES, shows that alternate excision using the wild-type
      end of IES2591 with an end from the internal IES is extremely rare or
      nonexistent. These results indicate that IESs are discrete elements whose
      excision depends upon nucleotides located within the consensus sequence, but also
      suggest that additional information is required to match one end of an IES with
      its excision partner.

PMID- 9927455
TI  - smg-7 is required for mRNA surveillance in Caenorhabditis elegans.
AB  - Eukaryotic mRNAs that contain premature stop codons are degraded more rapidly
      than their wild-type counterparts, a phenomenon termed "nonsense-mediated mRNA
      decay" (NMD) or "mRNA surveillance." Functions of six previously described
      Caenorhabditis elegans genes, smg-1 through smg-6, are required for NMD. Whereas
      nonsense mutant mRNAs are unstable in smg(+) genetic backgrounds, such mRNAs have
      normal stability in smg(-) backgrounds. Previous screens for smg mutations have
      likely not identified all genes involved in NMD, but efforts to identify
      additional smg genes are limited by the fact that almost 90% of smg mutations
      identified in genome-wide screens are alleles of smg-1, smg-2, or smg-5. We
      describe a modified screen for smg mutations that precludes isolating alleles of
      smg-1, smg-2, and smg-5. Using this screen, we have identified and cloned smg-7,
      a previously uncharacterized gene that we show is required for NMD. smg-7 is
      predicted to encode a novel protein that contains an acidic carboxyl terminus and
      two probable tetratricopeptide repeats. We provide evidence that smg-7 is
      cotranscribed with the previously characterized gene lin-45 and show that null
      alleles of smg-7 confer a temperature-sensitive defect in NMD.

PMID- 9927456
TI  - Genetic and molecular analysis of fox-1, a numerator element involved in
      Caenorhabditis elegans primary sex determination.
AB  - fox-1 was previously identified as a candidate numerator element based on its
      overexpression phenotype. FOX-1 is an RRM-type RNA-binding protein, which can
      bind RNAs in vitro. Western analysis detects FOX-1 throughout development. fox
      1::lacZ comes on ubiquitously early during embryogenesis. Postembryonically, fox
      1::lacZ is expressed sex specifically in a subset of cells in the head and tail.
      We describe a Tc1-derived deletion allele [fox-1(Delta)] that removes the RRM
      domain. fox-1(Delta) confers no phenotype in XXs, but can rescue XO-specific
      lethality and feminization caused by duplications of the left end of the X. fox
      1(Delta) synergizes with putative numerators, resulting in abnormal XX
      development. Genetic analysis indicated that fox-1(Delta) leads to a slight
      increase in xol-1 activity, while fox-1(gf) leads to partial loss of xol-1
      activity, and xol-1 is epistatic to fox-1. RNase protection experiments revealed
      increased levels of the 2.2-kb xol-1 message in fox-1(Delta) animals, and reduced
      levels in fox-1(gf) animals. Additionally, fox-1(Delta) impairs male mating
      efficiency, which, we propose, represents another function of fox-1, independent
      of xol-1 and its role in sex determination.

PMID- 9927458
TI  - Retrotransposable elements R1 and R2 in the rDNA units of Drosophila mercatorum:
      abnormal abdomen revisited.
AB  - R1 and R2 retrotransposable elements are stable components of the 28S rRNA genes
      of arthropods. While each retrotransposition event leads to incremental losses of
      rDNA unit expression, little is known about the selective consequences of these
      elements on the host genome. Previous reports suggested that in the abnormal
      abdomen (aa) phenotype of Drosophila mercatorum, high levels of rDNA insertions
      (R1) in conjunction with the under-replication locus (ur), enable the utilization
      of different ecological conditions via a population level shift to younger age.
      We have sequenced the R1 and R2 elements of D. mercatorum and show that the
      levels of R1- and R2-inserted rDNA units were inaccurately scored in the original
      studies of aa, leading to several misinterpretations. In particular, contrary to
      earlier reports, aa flies differentially underreplicate R1- and R2-inserted rDNA
      units, like other species of Drosophila. However, aa flies do not undergo the
      lower level of underreplication of their functional rDNA units (general
      underreplication) that is seen in wild-type strains. The lack of general
      underreplication is expected to confer a selective advantage and, thus, can be
      interpreted as an adaptation to overcome high levels of R1 and R2 insertions.
      These results allow us to reconcile some of the apparently contradictory effects
      of aa and the bobbed phenotype found in other species of Drosophila.

PMID- 9927457
TI  - An analysis of transvection at the yellow locus of Drosophila melanogaster.
AB  - Studies of a wide variety of organisms have shown that homologous sequences can
      exert a significant impact on each other, resulting in changes in gene sequence,
      gene expression, chromatin structure, and global chromosome architecture. Our
      work has focused on transvection, a process that can cause genes to be sensitive
      to the proximity of a homologue. Transvection is seen at the yellow gene of
      Drosophila, where it mediates numerous cases of intragenic complementation. In
      this article, we describe two approaches that have characterized the process of
      transvection at yellow. The first entailed a screen for mutations that support
      intragenic complementation at yellow. The second involved the analysis of 53
      yellow alleles, obtained from a variety of sources, with respect to
      complementation, molecular structure, and transcriptional competence. Our data
      suggest two ways in which transvection may be regulated at yellow: (1) a
      transcriptional mechanism, whereby the ability of an allele to support
      transvection is influenced by its transcriptional competency, and (2) a
      structural mechanism, whereby the pairing of structurally dissimilar homologues
      results in conformational changes that affect gene expression.

PMID- 9927459
TI  - A highly conserved sequence in the 3'-untranslated region of the drosophila Adh
      gene plays a functional role in Adh expression.
AB  - Phylogenetic analysis identified a highly conserved eight-base sequence
      (AAGGCTGA) within the 3'-untranslated region (UTR) of the Drosophila alcohol
      dehydrogenase gene, Adh. To examine the functional significance of this conserved
      motif, we performed in vitro deletion mutagenesis on the D. melanogaster Adh gene
      followed by P-element-mediated germline transformation. Deletion of all or part
      of the eight-base sequence leads to a twofold increase in in vivo ADH enzymatic
      activity. The increase in activity is temporally and spatially general and is the
      result of an underlying increase in Adh transcript. These results indicate that
      the conserved 3'-UTR motif plays a functional role in the negative regulation of
      Adh gene expression. The evolutionary significance of our results may be
      understood in the context of the amino acid change that produces the ADH-F allele
      and also leads to a twofold increase in ADH activity. While there is compelling
      evidence that the amino acid replacement has been a target of positive selection,
      the conservation of the 3'-UTR sequence suggests that it is under strong
      purifying selection. The selective difference between these two sequence changes,
      which have similar effects on ADH activity, may be explained by different
      metabolic costs associated with the increase in activity.

PMID- 9927460
TI  - Genetic analysis of hook, a gene required for endocytic trafficking in
      drosophila.
AB  - The Drosophila hook gene encodes a novel component of the endocytic compartment.
      Previously identified hook alleles, which still expressed truncated Hook
      proteins, affected the accumulation of internalized transmembrane ligands into
      multivesicular bodies (MVBs). To determine the hook null phenotype, we isolated
      nine new hook alleles on the basis of their characteristic hooked-bristle
      phenotype. At least one of these alleles, hk11, is a complete loss-of-function
      allele. Flies carrying the hk11 allele are viable and fertile but neither
      transmembrane ligands nor soluble ligands accumulate in MVBs. This effect on
      endocytosed ligands can be mimicked by the expression of Hook proteins truncated
      for the N- and C-terminal domains flanking the central coiled-coil region. The
      importance of all three domains for Hook function was confirmed by their
      conservation between two Drosophila and two human Hook proteins.

PMID- 9927461
TI  - Identification of genes controlling malpighian tubule and other epithelial
      morphogenesis in Drosophila melanogaster.
AB  - The Drosophila Malpighian tubule is a model system for studying genetic
      mechanisms that control epithelial morphogenesis. From a screen of 1800 second
      chromosome lethal lines, by observing uric acid deposits in unfixed inviable
      embryos, we identified five previously described genes (barr, fas, flb, raw, and
      thr) and one novel gene, walrus (wal), that affect Malpighian tubule
      morphogenesis. Phenotypic analysis of these mutant embryos allows us to place
      these genes, along with other previously described genes, into a genetic pathway
      that controls Malpighian tubule development. Specifically, wal affects
      evagination of the Malpighian tubule buds, fas and thr affect bud extension, and
      barr, flb, raw, and thr affect tubule elongation. In addition, these genes were
      found to have different effects on development of other epithelial structures,
      such as foregut and hindgut morphogenesis. Finally, from the same screen, we
      identified a second novel gene, drumstick, that affects only foregut and hindgut
      morphogenesis.

PMID- 9927462
TI  - A genetic screen for modifiers of drosophila Src42A identifies mutations in Egfr,
      rolled and a novel signaling gene.
AB  - Drosophila Src42A, a close relative of the vertebrate c-Src, has been implicated
      in the Ras-Mapk signaling cascade. An allele of Src42A, Su(Raf)1, dominantly
      suppresses the lethality of partial loss-of-function Raf mutations. To isolate
      genes involved in the same pathway where Src42A functions, we carried out genetic
      screens for dominant suppressor mutations that prevented Su(Raf)1 from
      suppressing Raf. Thirty-six mutations representing at least five genetic loci
      were recovered from the second chromosome. These are Drosophila EGF Receptor
      (Egfr), rolled, Src42A, and two other new loci, one of which was named semang
      (sag). During embryogenesis, sag affects the development of the head, tail, and
      tracheal branches, suggesting that it participates in the pathways of Torso and
      DFGF-R1 receptor tyrosine kinases. sag also disrupts the embryonic peripheral
      nervous system. During the development of imaginal discs, sag affects two
      processes known to require Egfr signaling: the recruitment of photoreceptor cells
      and wing vein formation. Thus sag functions in several receptor tyrosine kinase
      (RTK)-mediated processes. In addition, sag dominantly enhances the phenotypes
      associated with loss-of-function Raf and rl, but suppresses those of activated
      Ras1(V12) mutation. This work provides the first genetic evidence that both
      Src42A and sag are modulators of RTK signaling.

PMID- 9927463
TI  - Isolation and characterization of Drosophila retinal degeneration B suppressors.
AB  - The Drosophila retinal degeneration B protein (RdgB) is a novel integral membrane
      phosphatidylinositol transfer protein required for photoreceptor cell viability
      and light response. We isolated one intragenic suppressor (rdgBsu100) and four
      autosomal suppressors of the hypomorphic rdgBKS222 retinal degeneration
      phenotype. The rdgBsu100 suppressor dramatically slowed rdgBKS222's photoreceptor
      degeneration without significantly improving the electroretinogram (ERG) light
      response. One autosomal recessive suppressor [su(rdgB)69] significantly slowed
      rdgBKS222 retinal degeneration and restored the ERG light response near to that
      of the wild type. Unlike all the previously characterized rdgB suppressors, the
      four new autosomal suppressors do not affect the ERG light response in rdgB+
      flies. Only Su(rdgB)116 exhibited a mutant phenotype in a rdgB+ background, which
      was smaller R1-6 rhabdomeres. We also examined the extent to which two previously
      identified visual transduction mutations suppressed rdgB retinal degeneration.
      Absence of one of the light-activated calcium channels (trpCM) slowed the onset
      of rdgB-dependent degeneration. However, loss of protein kinase C (inaC209),
      which blocks photoreceptor cell deactivation, desensitization, and light
      adaptation, failed to suppress rdgB degeneration under normal light conditions.
      This demonstrates that TRP activity, but not INAC, is required for rapid rdgB
      dependent degeneration.

PMID- 9927464
TI  - The gene search system. A method for efficient detection and rapid molecular
      identification of genes in Drosophila melanogaster.
AB  - We have constructed a P-element-based gene search vector for efficient detection
      of genes in Drosophila melanogaster. The vector contains two copies of the
      upstream activating sequence (UAS) enhancer adjacent to a core promoter, one copy
      near the terminal inverted repeats at each end of the vector, and oriented to
      direct transcription outward. Genes were detected on the basis of phenotypic
      changes caused by GAL4-dependent forced expression of vector-flanking DNA, and
      the transcripts were identified with reverse transcriptase PCR (RT-PCR) using the
      vector-specific primer and followed by direct sequencing. The system had a
      greater sensitivity than those already in use for gain-of-function screening: 64%
      of the vector insertion lines (394/613) showed phenotypes with forced expression
      of vector-flanking DNA, such as lethality or defects in adult structure.
      Molecular analysis of 170 randomly selected insertions with forced expression
      phenotypes revealed that 21% matched the sequences of cloned genes, and 18%
      matched reported expressed sequence tags (ESTs). Of the insertions in cloned
      genes, 83% were upstream of the protein-coding region. We discovered two new
      genes that showed sequence similarity to human genes, Ras-related protein 2 and
      microsomal glutathione S-transferase. The system can be useful as a tool for the
      functional mapping of the Drosophila genome.

PMID- 9927465
TI  - Mosaic analysis in the drosophila ovary reveals a common hedgehog-inducible
      precursor stage for stalk and polar cells.
AB  - The fates of two small subgroups of the ovarian follicle cells appear to be
      linked: mutations in Notch, Delta, fs(1)Yb, or hedgehog cause simultaneous
      defects in the specification of stalk cells and polar cells. Both of these
      subgroups are determined in the germarium, and both cease division early in
      oogenesis. To test the possibility that these subgroups are related by lineage,
      we generated dominantly marked mitotic clones in ovaries. Small, restricted
      clones in stalk cells and polar cells were found adjacent to each other at a
      frequency much too high to be explained by independent induction. We therefore
      propose a model in which stalk cells and polar cells are derived from a precursor
      population that is distinct from the precursors for other follicle cells. We
      support and extend this model by characterization of mutants that affect stalk
      and polar cell formation. We find that ectopic expression of Hedgehog can induce
      both polar and stalk cell fate, presumably by acting on the precursor stage. In
      contrast, we find that stall affects neither the induction of the precursors nor
      the decision between the stalk cell and polar cell fate but, rather, some later
      differentiation step of stalk cells. In addition, we show that ectopic polar and
      stalk cells disturb the anterior-posterior polarity of the underlying oocyte.

PMID- 9927466
TI  - Genetic and molecular characterization of sting, a gene involved in crystal
      formation and meiotic drive in the male germ line of Drosophila melanogaster.
AB  - The sting mutation, caused by a P element inserted into polytene region 32D, was
      isolated by a screen for male sterile insertions in Drosophila melanogaster. This
      sterility is correlated with the presence of crystals in spermatocytes and
      spermatids that are structurally indistinguishable from those produced in males
      carrying a deficiency of the Y-linked crystal (cry) locus. In addition, their
      morphology is needle-like in Ste+ flies and star-shaped in Ste flies, once again
      as observed in cry- males. The sti mutation leads to meiotic drive of the sex
      chromosomes, and the strength of the phenomenon is correlated with the copy
      number of the repetitive Ste locus. The same correlation is also true for the
      penetrance of the male sterile mutation. A presumptive sti null allele results in
      male sterility and lethal maternal effect. The gene was cloned and shown to code
      for a putative protein that is 866 amino acids long. A C-terminal domain of 82
      amino acids is identified that is well conserved in proteins from different
      organisms. The gene is expressed only in the germline of both sexes. The
      interaction of sting with the Ste locus can also be demonstrated at the molecular
      level. While an unprocessed 8-kb Ste primary transcript is expressed in wild-type
      males, in X/Y homozygous sti males, as in X/Y cry- males, a 0.7-kb mRNA is
      produced.

PMID- 9927467
TI  - High-frequency retrotransposition of a marked I factor in Drosophila melanogaster
      correlates with a dynamic expression pattern of the ORF1 protein in the cytoplasm
      of oocytes.
AB  - To study the expression of the I factor, a non-long-terminal-repeat
      retrotransposon responsible for I-R hybrid dysgenesis in Drosophila melanogaster,
      we have tagged the ORF1 protein (ORF1p) by inserting the HA epitope in its N
      terminal region. In transgenic flies, this modification is compatible with a high
      rate of autonomous transposition and allows direct estimation of the
      transposition frequency. I factor transposes in the germline of females (SF) that
      are daughters from crosses between I strain males (which contain active copies of
      the I factor) and R strain females (which do not). We analyzed the expression
      pattern of ORF1p by indirect immunofluorescence. Its expression correlates with
      retrotransposition. During oogenesis ORF1p appears unexpectedly as a cytoplasmic
      product, which accumulates with a specific pattern into the oocyte. A comparison
      of the expression patterns under conditions that modify the transposing activity
      of the element clarifies some aspects of I-factor functioning in the
      transposition process.

PMID- 9927468
TI  - Intragenic sex-chromosomal crossovers of Xmrk oncogene alleles affect pigment
      pattern formation and the severity of melanoma in Xiphophorus.
AB  - The X and Y chromosomes of the platyfish (Xiphophorus maculatus) contain a region
      that encodes several important traits, including the determination of sex,
      pigment pattern formation, and predisposition to develop malignant melanoma.
      Several sex-chromosomal crossovers were identified in this region. As the
      melanoma-inducing oncogene Xmrk is the only molecularly identified constituent,
      its genomic organization on both sex chromosomes was analyzed in detail. Using X
      and Y allele-specific sequence differences a high proportion of the crossovers
      was found to be intragenic in the oncogene Xmrk, concentrating in the
      extracellular domain-encoding region. The genetic and molecular data allowed
      establishment of an order of loci over approximately 0.6 cM. It further revealed
      a sequence located within several kilobases of the extracellular domain-encoding
      region of Xmrk that regulates overexpression of the oncogene.

PMID- 9927470
TI  - The use of microsatellite variation to infer population structure and demographic
      history in a natural model system.
AB  - To assess the reliability of genetic markers it is important to compare
      inferences that are based on them to a priori expectations. In this article we
      present an analysis of microsatellite variation within and among populations of
      island foxes (Urocyon littoralis) on California's Channel Islands. We first show
      that microsatellite variation at a moderate number of loci (19) can provide an
      essentially perfect description of the boundaries between populations and an
      accurate representation of their historical relationships. We also show that the
      pattern of variation across unlinked microsatellite loci can be used to test
      whether population size has been constant or increasing. Application of these
      approaches to the island fox system indicates that microsatellite variation may
      carry considerably more information about population history than is currently
      being used.

PMID- 9927469
TI  - Multiple-trait quantitative trait loci analysis using a large mouse sibship.
AB  - Quantitative trait loci influencing several phenotypes were assessed using a
      genetically heterogeneous mouse population. The 145 individuals were produced by
      a cross between (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males.
      The population is genetically equivalent to full siblings derived from
      heterozygous parents, with known linkage phase. Each individual in the population
      represents a unique combination of alleles from the inbred grandparents.
      Quantitative phenotypes for eight T cell measures were obtained at 8 and 18 mo of
      age. Single-marker locus, repeated measures analysis of variance identified nine
      marker-phenotype associations with an experimentwise significance level of P <
      0.05. Six of the eight quantitative phenotypes could be associated with at least
      one locus having experiment-wide significance. Composite interval, repeated
      measures analysis of variance identified 13 chromosomal regions with
      comparisonwise (nominal) significance associations of P < 0.001. The heterozygous
      parent cross provides a reproducible, general method for identification of loci
      associated with quantitative trait phenotypes or repeated phenotypic measures.

PMID- 9927471
TI  - A second-generation genetic linkage map of the domestic dog, Canis familiaris.
AB  - Purebred strains, pronounced phenotypic variation, and a high incidence of
      heritable disease make the domestic dog uniquely suited to complement genetic
      analyses in humans and mice. A comprehensive genetic linkage map would afford
      many opportunities in dogs, ranging from the positional cloning of disease genes
      to the dissection of quantitative differences in size, shape, and behavior. Here
      we report a canine linkage map with the number of mapped loci expanded to 276 and
      10-cM coverage extended to 75-90% of the genome. Most of the 38 canine autosomes
      are likely represented in the collection of 39 autosomal linkage groups. Eight
      markers were sufficiently informative to detect linkage at distances of 10-13 cM,
      yet remained unlinked to any other marker. Taken together, the results suggested
      a genome size of about 27 M. As in other species, the genetic length varied
      between sexes, with the female autosomal distance being approximately 1.4-fold
      greater than that of male meioses. Fifteen markers anchored well-described genes
      on the map, thereby serving as landmarks for comparative mapping in dogs. We
      discuss the utility of the current map and outline steps necessary for future map
      improvement.

PMID- 9927472
TI  - A candidate recombination modifier gene for Zea mays L.
AB  - Maize meiotic mutant desynaptic (dy) was tested as a candidate recombination
      modifier gene because its effect is manifested in prophase I. Recombination rates
      for desynaptic (dy) and its wild type were compared in two ways: (1) segregation
      analysis using six linked molecular markers on chromosome 1L and (2) cytogenetic
      analysis using fluorescence in situ hybridization (FISH)-aided meiotic
      configurations observed in metaphase I. Chromosome 1L map lengths among the six
      linked markers were 45-63 cM for five F2 dy/dy plants, significantly lower than
      the wild-type F2 map distance of 72 cM. Chromosomes 2 and 6 were marked with rDNA
      FISH probes, and their map lengths were estimated from FISH-adorned meiotic
      configurations using the expectation-maximization algorithm. Chiasma frequencies
      for dy/dy plants were significantly reduced for both arms of chromosome 2, for
      chromosome arm 6L, and for eight unidentified chromosomes. There was a notable
      exception for the nucleolus-organizing region-bearing arm chromosome arm 6S,
      where dy increased chiasma frequency. Maize meiotic mutant desynaptic is a
      recombination modifier gene based on cytogenetic and segregation analyses.

PMID- 9927473
TI  - Meiotically and mitotically stable inheritance of DNA hypomethylation induced by
      ddm1 mutation of Arabidopsis thaliana.
AB  - In contrast to mammalian epigenetic phenomena, where resetting of gene expression
      generally occurs in each generation, epigenetic states of plant genes are often
      stably transmitted through generations. The Arabidopsis mutation ddm1 causes a
      70% reduction in genomic 5-methylcytosine level. We have previously shown that
      the ddm1 mutation results in an accumulation of a variety of developmental
      abnormalities by slowly inducing heritable changes in other loci. Each of the
      examined ddm1-induced developmental abnormalities is stably transmitted even when
      segregated from the potentiating ddm1 mutation. Here, the inheritance of DNA
      hypomethylation induced by ddm1 was examined in outcross progeny by HPLC and
      Southern analyses. The results indicate that (i) DDM1 gene function is not
      necessary during the gametophyte stage, (ii) ddm1 mutation is completely
      recessive, and (iii) remethylation of sequences hypomethylated by the ddm1
      mutation is extremely slow or nonexistent even in wild-type DDM1 backgrounds. The
      stable transmission of DNA methylation status may be related to the meiotic
      heritability of the ddm1-induced developmental abnormalities.

PMID- 9927474
TI  - Molecular population genetics of floral homeotic loci. Departures from the
      equilibrium-neutral model at the APETALA3 and PISTILLATA genes of Arabidopsis
      thaliana.
AB  - Molecular variation in genes that regulate development provides insights into the
      evolutionary processes that shape the diversification of morphogenetic pathways.
      Intraspecific sequence variation at the APETALA3 and PISTILLATA floral homeotic
      genes of Arabidopsis thaliana was analyzed to infer the extent and nature of
      diversity at these regulatory loci. Comparison of AP3 and PI diversity with three
      previously studied genes revealed several features in the patterning of
      nucleotide polymorphisms common between Arabidopsis nuclear loci, including an
      excess of low-frequency nucleotide polymorphisms and significantly elevated
      levels of intraspecific replacement variation. This pattern suggests that A.
      thaliana has undergone recent, rapid population expansion and now exists in
      small, inbred subpopulations. The elevated intraspecific replacement levels may
      thus represent slightly deleterious polymorphisms that differentiate distinct
      ecotypes. The distribution of replacement and synonymous changes in AP3 and PI
      core and noncore functional domains also indicates differences in the patterns of
      molecular evolution between these interacting floral regulatory genes.

PMID- 9927475
TI  - Isolation of ethyl methanesulfonate-induced gametophytic mutants in Arabidopsis
      thaliana by a segregation distortion assay using the multimarker chromosome 1.
AB  - The life cycle of plants comprises two alternating generations, the diploid
      sporophyte (spore-bearing plant) and the haploid gametophyte (gamete-bearing
      plant). In contrast to animals, the postmeiotic cells give rise to haploid
      organisms whose function is to produce the gametes and to mediate fertilization.
      Analysis of gametophyte development and function has been hampered by the
      difficulty of identifying haplo-phase-specific mutants in conventional
      mutagenesis screens. Here we use a genetic strategy that is based on segregation
      distortion of nearby visible markers to screen for EMS-induced gametophytic
      mutants in Arabidopsis thaliana. Using the multiple marker chromosome mm1 we have
      isolated seven lines that displayed an altered segregation of markers. Reciprocal
      backcrosses of these lines showed a marked reduction of the transmission of the
      male and/or female gametes. Phenotypic analysis revealed that different aspects
      of either gametophytic development or function were affected. Three male
      gametophytic lines showed specific arrests during pollen development. One male
      gametophytic line was specifically defective in pollen tube elongation. Three
      gametophytic lines showed variable defects in both male and female gametophytic
      development.

PMID- 9927476
TI  - The reinforcement of mating preferences on an island.
AB  - We develop a haploid model for the reinforcement of female mating preferences on
      an island that receives migrants from a continent. We find that preferences will
      evolve to favor island males under a broad range of conditions: when the average
      male display trait on the island and continent differ, when the preference acts
      on that difference, and when there is standing genetic variance for the
      preference. A difference between the mean display trait on the continent and on
      the island is sufficient to drive reinforcement of preferences. Additional
      postzygotic isolation, caused, for example, by either epistatic incompatibility
      or ecological selection against hybrids, will amplify reinforcement but is not
      necessary. Under some conditions, the degree of preference reinforcement is a
      simple function of quantities that can be estimated entirely from phenotypic
      data. We go on to study how postzygotic isolation caused by epistatic
      incompatibilities affects reinforcement of the preference. With only one pair of
      epistatic loci, reinforcement is enhanced by tighter linkage between the
      preference genes and the genes causing hybrid incompatibility. Reinforcement of
      the preference is also affected by the number of epistatically interacting genes
      involved in incompatibility, independent of the overall intensity of selection
      against hybrids.

PMID- 9927477
TI  - Multiple-trait mapping of quantitative trait loci after selective genotyping
      using logistic regression.
AB  - Experiments to map QTL usually measure several traits, and not uncommonly
      genotype only those animals that are extreme for some trait(s). Analysis of
      selectively genotyped, multiple-trait data presents special problems, and most
      simple methods lead to biased estimates of the QTL effects. The use of logistic
      regression to estimate QTL effects is described, where the genotype is treated as
      the dependent variable and the phenotype as the independent variable. In this way
      selection on phenotype does not bias the results. If normally distributed errors
      are assumed, the logistic-regression analysis is almost equivalent to a maximum
      likelihood analysis, but can be carried out with standard statistical packages.
      Analysis of a simulated half-sib experiment shows that logistic regression can
      estimate the effect and position of a QTL without bias and confirms the increased
      power achieved by multiple-trait analysis.

PMID- 9927478
TI  - The effect of overdominance on characterizing deleterious mutations in large
      natural populations.
AB  - Alternatives to the mutation-accumulation approach have been developed to
      characterize deleterious genomic mutations. However, they all depend on the
      assumption that the standing genetic variation in natural populations is solely
      due to mutation-selection (M-S) balance and therefore that overdominance does not
      contribute to heterosis. Despite tremendous efforts, the extent to which this
      assumption is valid is unknown. With different degrees of violation of the M-S
      balance assumption in large equilibrium populations, we investigated the
      statistical properties and the robustness of these alternative methods in the
      presence of overdominance. We found that for dominant mutations, estimates for U
      (genomic mutation rate) will be biased upward and those for h (mean dominance
      coefficient) and s (mean selection coefficient), biased downward when additional
      overdominant mutations are present. However, the degree of bias is generally
      moderate and depends largely on the magnitude of the contribution of overdominant
      mutations to heterosis or genetic variation. This renders the estimates of U and
      s not always biased under variable mutation effects that, when working alone,
      cause U and s to be underestimated. The contributions to heterosis and genetic
      variation from overdominant mutations are monotonic but not linearly proportional
      to each other. Our results not only provide a basis for the correct inference of
      deleterious mutation parameters from natural populations, but also alleviate the
      biggest concern in applying the new approaches, thus paving the way for reliably
      estimating properties of deleterious mutations.

PMID- 9927479
TI  - Assessing the quality of the DNA sequence from the Human Genome Project.

PMID- 9927480
TI  - Genomics and hearing impairment.
AB  - Hearing impairment is clinically and genetically heterogeneous. There are >400
      disorders in which hearing impairment is a characteristic of the syndrome, and
      family studies demonstrate that there are at least 30 autosomal loci for
      nonsyndromic hearing impairment. The genes that have been identified encode
      diaphanous (HDIA1), alpha-tectorin (TECTA), the transcription factor POU4F3,
      connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15), and four
      novel proteins (PDS, COCH, DFNA5, DFNB9). The same clinical phenotype in hearing
      impaired individuals, even those within the same family, can result from
      mutations in different genes. Conversely, mutations in the same gene can result
      in a variety of clinical phenotypes with different modes of inheritance. For
      example, mutations in the gene encoding MYO7A cause Usher syndrome type IB,
      autosomal-recessive nonsyndromic hearing impairment (DFNB2), and autosomal
      dominant nonsyndromic hearing impairment (DFNA11). Additionally, the mouse
      ortholog of the MYO7A gene is the shaker-1 gene. Mouse models such as shaker-1
      have facilitated the identification of genes that cause hearing impairment in
      humans. The availability of high-resolution maps of the human and mouse genomes
      and new technologies for gene identification are advancing molecular
      understanding of hearing impairment and the complex mechanisms of the auditory
      system.

PMID- 9927481
TI  - Distribution of protein folds in the three superkingdoms of life.
AB  - A sensitive protein-fold recognition procedure was developed on the basis of
      iterative database search using the PSI-BLAST program. A collection of 1193
      position-dependent weight matrices that can be used as fold identifiers was
      produced. In the completely sequenced genomes, folds could be automatically
      identified for 20%-30% of the proteins, with 3%-6% more detectable by additional
      analysis of conserved motifs. The distribution of the most common folds is very
      similar in bacteria and archaea but distinct in eukaryotes. Within the bacteria,
      this distribution differs between parasitic and free-living species. In all
      analyzed genomes, the P-loop NTPases are the most abundant fold. In bacteria and
      archaea, the next most common folds are ferredoxin-like domains, TIM-barrels, and
      methyltransferases, whereas in eukaryotes, the second to fourth places belong to
      protein kinases, beta-propellers and TIM-barrels. The observed diversity of
      protein folds in different proteomes is approximately twice as high as it would
      be expected from a simple stochastic model describing a proteome as a finite
      sample from an infinite pool of proteins with an exponential distribution of the
      fold fractions. Distribution of the number of domains with different folds in one
      protein fits the geometric model, which is compatible with the evolution of
      multidomain proteins by random combination of domains. [Fold predictions for
      proteins from 14 proteomes are available on the World Wide Web at. The FIDs are
      available by anonymous ftp at the same location.]

PMID- 9927482
TI  - AAA+: A class of chaperone-like ATPases associated with the assembly, operation,
      and disassembly of protein complexes.
AB  - Using a combination of computer methods for iterative database searches and
      multiple sequence alignment, we show that protein sequences related to the AAA
      family of ATPases are far more prevalent than reported previously. Among these
      are regulatory components of Lon and Clp proteases, proteins involved in DNA
      replication, recombination, and restriction (including subunits of the origin
      recognition complex, replication factor C proteins, MCM DNA-licensing factors and
      the bacterial DnaA, RuvB, and McrB proteins), prokaryotic NtrC-related
      transcription regulators, the Bacillus sporulation protein SpoVJ, Mg2+, and Co2+
      chelatases, the Halobacterium GvpN gas vesicle synthesis protein, dynein motor
      proteins, TorsinA, and Rubisco activase. Alignment of these sequences, in light
      of the structures of the clamp loader delta' subunit of Escherichia coli DNA
      polymerase III and the hexamerization component of N-ethylmaleimide-sensitive
      fusion protein, provides structural and mechanistic insights into these proteins,
      collectively designated the AAA+ class. Whole-genome analysis indicates that this
      class is ancient and has undergone considerable functional divergence prior to
      the emergence of the major divisions of life. These proteins often perform
      chaperone-like functions that assist in the assembly, operation, or disassembly
      of protein complexes. The hexameric architecture often associated with this class
      can provide a hole through which DNA or RNA can be thread; this may be important
      for assembly or remodeling of DNA-protein complexes.

PMID- 9927483
TI  - Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal
      chromosome 11q.
AB  - Jacobsen syndrome is a haploinsufficiency disorder caused, most frequently by
      terminal deletion of part of the long arm of chromosome 11, with breakpoints in
      11q23.3-11q24.2. Inheritance of an expanded p(CCG)n trinucleotide repeat at the
      folate-sensitive fragile site FRA11B has been implicated in the generation of the
      chromosome breakpoint in several Jacobsen syndrome patients. The majority of such
      breakpoints, however, map distal to this fragile site and are not linked with its
      expression. To characterize these distal breakpoints and ultimately to further
      investigate the mechanisms of chromosome breakage, a 40-Mb YAC contig covering
      the distal long arm of chromosome 11 was assembled. The utility of the YAC contig
      was demonstrated in three ways: (1) by rapidly mapping the breakpoints from two
      new Jacobsen syndrome patients using FISH; (2) by demonstrating conversion to
      high resolution PAC contigs after direct screening of PAC library filters with a
      YAC clone containing a Jacobsen syndrome breakpoint; and (3) by placing 23
      Jacobsen syndrome breakpoints on the physical map. This analysis has suggested
      the existence of at least two new Jacobsen syndrome breakpoint cluster regions in
      distal chromosome 11.

PMID- 9927484
TI  - Comparative sequence of human and mouse BAC clones from the mnd2 region of
      chromosome 2p13.
AB  - The mnd2 mutation on mouse chromosome 6 produces a progressive neuromuscular
      disorder. To determine the gene content of the 400-kb mnd2 nonrecombinant region,
      we sequenced 108 kb of mouse genomic DNA and 92 kb of human genomic sequence from
      the corresponding region of chromosome 2p13.3. Three genes with the indicated
      sizes and intergenic distances were identified: D6Mm5e (>/=81 kb)-787 bp-DOK (2
      kb)-845 bp-LOR2 (>/=6 kb). D6Mm5e is expressed in many tissues at very low
      abundance and the predicted 526-residue protein contains no known functional
      domains. DOK encodes the p62(dok) rasGAP binding protein involved in signal
      transduction. LOR2 encodes a novel lysyl oxidase-related protein of 757 amino
      acid residues. We describe a simple search protocol for identification of
      conserved internal exons in genomic sequence. Evolutionary conservation proved to
      be a useful criterion for distinguishing between authentic exons and artifactual
      products obtained by exon amplification, RT-PCR, and 5' RACE. Conserved noncoding
      sequence elements longer than 80 bp with >/=75% nucleotide sequence identity
      comprise approximately 1% of the genomic sequence in this region. Comparative
      analysis of this human and mouse genomic DNA sequence was an efficient method for
      gene identification and is independent of developmental stage or quantitative
      level of gene expression. [The sequence data described in this paper have been
      submitted to the GenBank data library under the following accession numbers:
      AC003061, mouse BAC clone 245c12; AC003065, human BAC clone h173(E10); AF053368,
      mouse Lor2 cDNA; AF084363, 108-kb contig from mouse BAC 245c12; AF084364, mouse
      D6Mm5e cDNA.]

PMID- 9927485
TI  - Mapping ESTs by fiber-FISH.
AB  - A visual transcript map of six genes was constructed on the chromosome 21q22.3 by
      high resolution fluorescence in situ hybridization (FISH). Expressed sequence
      tags (ESTs) from six genes-PWP2, KNP1, AIRE, C21orf3, SMT3A, and C21orf1-were
      successfully localized by fiber-FISH by use of sensitive tyramide-based
      detection. The sizes of the ESTs varied between 315 to 956 bp and most of them
      map within the 3'-untranslated region. The ESTs were assigned to and subsequently
      ordered within cosmid, PAC, and BAC clones hybridized on DNA fibers. Physical
      distances between ESTs and known markers were determined. Our results demonstrate
      the feasibility and accuracy of visual mapping EST sequences in relation to known
      markers. The main advantage of this approach is that it can be applied to finely
      map any of the database ESTs for positional cloning efforts. The sensitivity,
      specificity, and reproducibility of this high-resolution EST mapping technique is
      evaluated.

PMID- 9927486
TI  - Single-tube genotyping without oligonucleotide probes.
AB  - We report the development of a self-contained (homogeneous), single-tube assay
      for the genotyping of single-nucleotide polymorphisms (SNPs), which does not rely
      on fluorescent oligonucleotide probes. The method, which we call Tm-shift
      genotyping, combines allele-specific PCR with the discrimination between
      amplification products by their melting temperatures (Tm). Two distinct forward
      primers, each of which contains a 3'-terminal base that corresponds to one of the
      two SNP allelic variants, are combined with a common reverse primer in a single
      tube reaction. A GC-tail is attached to one of the forward allele-specific
      primers to increase the Tm of the amplification product from the corresponding
      allele. PCR amplification, Tm analysis, and allele determination of genomic
      template DNA are carried out on a fluorescence-detecting thermocycler with a dye
      that fluoresces when bound to dsDNA. We demonstrate the accuracy and reliability
      of Tm-shift genotyping on 100 samples typed for two SNPs, and recommend it both
      as a simple and inexpensive diagnostic tool for genotyping medically relevant
      SNPs and as a high-throughput SNP genotyping method for gene mapping.

PMID- 9927487
TI  - Error checking and graphical representation of multiple-complete-digest (MCD)
      restriction-fragment maps.
AB  - Genetic and physical maps display the relative positions of objects or markers
      occurring within a target DNA molecule. In constructing maps, the primary
      objective is to determine the ordering of these objects. A further objective is
      to assign a coordinate to each object, indicating its distance from a reference
      end of the target molecule. This paper describes a computational method and a
      body of software for assigning coordinates to map objects, given a solution or
      partial solution to the ordering problem. We describe our method in the context
      of multiple-complete-digest (MCD) mapping, but it should be applicable to a
      variety of other mapping problems. Because of errors in the data or insufficient
      clone coverage to uniquely identify the true ordering of the map objects, a
      partial ordering is typically the best one can hope for. Once a partial ordering
      has been established, one often seeks to overlay a metric along the map to assess
      the distances between the map objects. This problem often proves intractable
      because of data errors such as erroneous local length measurements (e.g., large
      clone lengths on low-resolution physical maps). We present a solution to the
      coordinate assignment problem for MCD restriction-fragment mapping, in which a
      coordinated set of single-enzyme restriction maps are simultaneously constructed.
      We show that the coordinate assignment problem can be expressed as the solution
      of a system of linear constraints. If the linear system is free of
      inconsistencies, it can be solved using the standard Bellman-Ford algorithm. In
      the more typical case where the system is inconsistent, our program perturbs it
      to find a new consistent system of linear constraints, close to those of the
      given inconsistent system, using a modified Bellman-Ford algorithm. Examples are
      provided of simple map inconsistencies and the methods by which our program
      detects candidate data errors and directs the user to potential suspect regions
      of the map.

PMID- 9927488
TI  - "KARIBIN," an information resource for obtaining genomic information in a
      cytogenetic band.
AB  - KARIBIN () is a karyotypic region-based integrated information resource that
      provides a comprehensive view of the integrated mapping and sequencing data for
      the human genome. A cytogenetic band is linked to a genetic or physical location
      using fluorescence in situ hybridization (FISH) mapping data. The genetic,
      physical mapping data and the sequencing data are integrated using STS markers
      positioned on multiple maps. For each cytogenetic band, the user can obtain the
      most up-to-date information that includes genetic and physical maps, human
      transcript gene map, YAC and PAC/BAC clone coverage, disease gene phenotype, and
      high throughput genomic sequences from the major human genome sequencing centers.
      This information provides a framework for future experiments and may accelerate
      the process of disease gene hunting. It is envisioned that other cytogenetic
      based information such as chromosome aberrations can be linked to this framework.

PMID- 9927489
TI  - The innate immune system in cystic fibrosis lung disease.

PMID- 9927490
TI  - The genesis of cystic fibrosis lung disease.

PMID- 9927491
TI  - Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in
      rats.
AB  - A fatty liver is characterized by the hyperaccumulation of lipids within
      hepatocytes and is often caused by excessive alcohol intake. Rats fed ethanol
      containing diets for 37 days showed remarkable increase in hepatic lipids and
      lipid droplet accumulation in the hepatocytes, indicating the onset of alcoholic
      fatty liver. Administration of hepatocyte growth factor (HGF) for the last seven
      days of ethanol treatment markedly decreased hepatic lipids to a level lower than
      that seen before HGF treatment. In contrast, serum levels of lipids and
      lipoproteins increased with HGF administration. Primary cultured hepatocytes
      prepared from the fatty liver retained lipid droplets during a 48-hour culture.
      However, when cultured in the presence of HGF, intracellular lipid concentrations
      decreased and lipid secretion was enhanced. Consistent with these events, HGF
      stimulated the rate of protein synthesis of apolipoprotein B (apoB) and enhanced
      subsequent mobilization of lipids into the medium. These results indicate that
      HGF administration induced recovery from the fatty liver, at least in part, by
      enhancing apoB synthesis and the subsequent mobilization of lipids from
      hepatocytes with fatty change. The possibility that HGF can be therapeutic for
      subjects with an alcohol-related fatty liver warrants further attention.

PMID- 9927492
TI  - p27(kip1) acts as a downstream effector of and is coexpressed with the beta1C
      integrin in prostatic adenocarcinoma.
AB  - Integrins are a large family of transmembrane receptors that, in addition to
      mediating cell adhesion, modulate cell proliferation. The beta1C integrin is an
      alternatively spliced variant of the beta1 subfamily that contains a unique 48
      amino acid sequence in its cytoplasmic domain. We have shown previously that in
      vitro beta1C inhibits cell proliferation and that in vivo beta1C is expressed in
      nonproliferative, differentiated epithelium and is selectively downregulated in
      prostatic adenocarcinoma. Here we show, by immunohistochemistry and
      immunoblotting analysis, that beta1C is coexpressed in human prostate epithelial
      cells with the cell-cycle inhibitor p27(kip1), the loss of which correlates with
      poor prognosis in prostate cancer. In the 37 specimens analyzed, beta1C and
      p27(kip1) are concurrently expressed in 93% of benign and 84%-91% of tumor
      prostate cells. Forced expression of beta1C in vitro is accompanied by an
      increase in p27(kip1) levels, by inhibition of cyclin A-dependent kinase
      activity, and by increased association of p27(kip1) with cyclin A. beta1C
      inhibitory effect on cell proliferation is completely prevented by p27(kip1)
      antisense, but not mismatch oligonucleotides. beta1C expression does not affect
      either cyclin A or E levels, or cyclin E-associated kinase activity, nor the
      mitogen-activated protein (MAP) kinase pathway. These findings show a unique
      mechanism of cell growth inhibition by integrins and point to beta1C as an
      upstream regulator of p27(kip1) expression and, therefore, a potential target for
      tumor suppression in prostate cancer.

PMID- 9927493
TI  - Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton
      abnormalities.
AB  - A diverse family of protein 4.1R isoforms is encoded by a complex gene on human
      chromosome 1. Although the prototypical 80-kDa 4.1R in mature erythrocytes is a
      key component of the erythroid membrane skeleton that regulates erythrocyte
      morphology and mechanical stability, little is known about 4.1R function in
      nucleated cells. Using gene knockout technology, we have generated mice with
      complete deficiency of all 4.1R protein isoforms. These 4.1R-null mice were
      viable, with moderate hemolytic anemia but no gross abnormalities. Erythrocytes
      from these mice exhibited abnormal morphology, lowered membrane stability, and
      reduced expression of other skeletal proteins including spectrin and ankyrin,
      suggesting that loss of 4. 1R compromises membrane skeleton assembly in erythroid
      progenitors. Platelet morphology and function were essentially normal, indicating
      that 4.1R deficiency may have less impact on other hematopoietic lineages.
      Nonerythroid 4.1R expression patterns, viewed using histochemical staining for
      lacZ reporter activity incorporated into the targeted gene, revealed focal
      expression in specific neurons in the brain and in select cells of other major
      organs, challenging the view that 4.1R expression is widespread among
      nonerythroid cells. The 4.1R knockout mice represent a valuable animal model for
      exploring 4.1R function in nonerythroid cells and for determining
      pathophysiological sequelae to 4.1R deficiency.

PMID- 9927494
TI  - Biologic significance of angiopoietin-2 expression in human hepatocellular
      carcinoma.
AB  - Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but
      the mechanisms of neovascularization that permit rapid growth have not been
      defined. Angiopoietins (Ang) recently have been identified as ligands for
      vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important
      growth factors in the generation of new blood vessels. We investigated Ang
      expression in 23 samples of HCC and paired adjacent uninvolved liver samples to
      determine if these genes have a potential role in the growth and spread of this
      disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was
      obtained from HCC specimens, and the biologic consequences of overexpression on
      tumor formation and hemorrhage were determined in an animal model system.
      Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous
      liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor
      tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only
      in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC
      cells promotes the rapid development of human hepatomas and produces hemorrhage
      within tumors in nude mice. These results suggest a role for Ang2 in the
      neovascularization of HCC. This enhanced gene expression may contribute to the
      clinical hypervascular phenotype, as well as tumor formation and progression.

PMID- 9927495
TI  - Neuroprotective effects of gelsolin during murine stroke.
AB  - Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and
      voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury
      following brain ischemia. The activity of these channels is modulated by dynamic
      changes in the actin cytoskeleton, which may occur, in part, through the actions
      of the actin filament-severing protein gelsolin. We show that gelsolin-null
      neurons have enhanced cell death and rapid, sustained elevation of Ca2+ levels
      following glucose/oxygen deprivation, as well as augmented cytosolic Ca2+ levels
      in nerve terminals following depolarization in vitro. Moreover, major increases
      in infarct size are seen in gelsolin-null mice after reversible middle cerebral
      artery occlusion, compared with controls. In addition, treatment with
      cytochalasin D, a fungal toxin that depolymerizes actin filaments, reduced the
      infarct size of both gelsolin-null and control mice to the same final volume.
      Hence, enhancement or mimicry of gelsolin activity may be neuroprotective during
      stroke.

PMID- 9927496
TI  - The molecular basis for apoptotic defects in patients with CD95 (Fas/Apo-1)
      mutations.
AB  - Heterozygous mutations of the receptor CD95 (Fas/Apo-1) are associated with
      defective lymphocyte apoptosis and a clinical disease characterized by
      lymphadenopathy, splenomegaly, and systemic autoimmunity. From our cohort of 11
      families, we studied eight patients to define the mechanisms responsible for
      defective CD95-mediated apoptosis. Mutations in and around the death domain of
      CD95 had a dominant-negative effect that was explained by interference with the
      recruitment of the signal adapter protein, FADD, to the death domain. The
      intracellular domain (ICD) mutations were associated with a highly penetrant
      Canale-Smith syndrome (CSS) phenotype and an autosomal dominant inheritance
      pattern. In contrast, mutations affecting the CD95 extracellular domain (ECD)
      resulted in failure of extracellular expression of the mutant protein or impaired
      binding to CD95 ligand. They did not have a dominant-negative effect. In each of
      the families with an ECD mutation, only a single individual was affected. These
      observations were consistent with differing mechanisms of action and modes of
      inheritance of ICD and ECD mutations, suggesting that individuals with an ECD
      mutation may require additional defect(s) for expression of CSS.

PMID- 9927497
TI  - The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal
      subjects.
AB  - We have quantitatively determined gluconeogenesis (GNG) from all precursors,
      using a novel method employing 2H20 to address the question of whether changes in
      plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the
      first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic
      acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after
      administration of NA). FFA decreased from 387 microM at 16 hours to 43 microM at
      20 hours, and then rebounded to 1,823 microM at 24 hours. GNG decreased from
      58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P <
      0.005) and then rebounded to 78. 9% at 24 hours (P < 0.05). Conversely,
      glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P <
      0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study
      (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the
      last meal. FFA rose from 423 to 681 microM (P < 0.05), and GNG from 50.3% to
      61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous
      glucose production decreased at the same rate in both studies, from 10.7 to 8.6
      micromol/kg/min (P < 0. 05). In study 3 (n = 6), in which the NA-mediated
      decrease of plasma FFA was prevented by infusion of lipid and heparin, neither
      FFA nor GNG changed significantly. In summary, our data suggest that (a) acute
      changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL;
      (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in
      GL; and (c) NA has no direct effect on GNG.

PMID- 9927498
TI  - Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone
      related peptide receptor expression in bone and cartilage.
AB  - Transcription of the mouse parathyroid hormone (PTH)/PTH-related peptide (PTHrP)
      receptor (PTHR) gene is controlled by promoters P1 and P2. We performed
      transcript-specific in situ hybridization and found that P2 is the predominant
      promoter controlling PTHR gene expression in bone and cartilage. Treatment with
      1alpha, 25-dihydroxyvitamin D3 (D3) in vivo specifically downregulated P2
      specific transcripts in osteoblasts, but not in chondrocytes, under conditions
      where it enhanced bone resorption. Treatment of the osteoblastic cell line MC3T3
      E1 with D3 in vitro reduced expression of both P2-specific transcripts and PTHR
      protein. This effect was not blocked by cycloheximide, indicating that D3
      inhibits PTHR expression by downregulating transcription of the P2 promoter. A
      similar inhibitory effect of D3 was not observed in the chondrocytic cell line
      CFK2. Gene-transfer experiments showed that P2, but not P1, is active in both
      MC3T3-E1 and CFK2 cells, and that D3 specifically inhibited P2 promoter activity
      in MC3T3-E1, but not in CFK2 cells. Inhibition of P2 activity by D3 required
      promoter sequences lying more that 1.6 kb upstream of the P2 transcription start
      site. Thus, the P2 promoter controls PTHR gene expression in both osteoblasts and
      chondrocytes. D3 downregulates PTHR gene transcription in a cell-specific manner
      by inhibiting P2 promoter activity in osteoblasts, but not in chondrocytes.

PMID- 9927499
TI  - The cholecystokinin-A receptor mediates inhibition of food intake yet is not
      essential for the maintenance of body weight.
AB  - Food intake and body weight are determined by a complex interaction of regulatory
      pathways. To elucidate the contribution of the endogenous peptide
      cholecystokinin, mice lacking functional cholecystokinin-A receptors were
      generated by targeted gene disruption. To explore the role of the cholecystokinin
      A receptor in mediating satiety, food intake of cholecystokinin-A receptor-/-
      mice was compared with the corresponding intakes of wild-type animals and mice
      lacking the other known cholecystokinin receptor subtype, cholecystokinin
      B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease
      food intake in mice lacking cholecystokinin-A receptors. In contrast,
      cholecystokinin diminished food intake by up to 90% in wild-type and
      cholecystokinin-B/gastrin receptor-/- mice. Together, these findings indicate
      that cholecystokinin-induced inhibition of food intake is mediated by the
      cholecystokinin-A receptor. To explore the long-term consequences of either
      cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a
      function of age was compared between freely fed wild-type and mutant animals.
      Both cholecystokinin-A and cholecystokinin-B/gastrin receptor-/- mice maintained
      normal body weight well into adult life. In addition, each of the two receptor-/-
      strains had normal pancreatic morphology and were normoglycemic. Our results
      suggest that although cholecystokinin plays a role in the short-term inhibition
      of food intake, this pathway is not essential for the long-term maintenance of
      body weight.

PMID- 9927500
TI  - Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates
      intracellular transfer of nitric oxide.
AB  - Since thiols can undergo nitrosation and the cell membrane is rich in thiol
      containing proteins, we considered the possibility that membrane surface thiols
      may regulate cellular entry of NO. Recently, protein disulfide isomerase (PDI), a
      protein that catalyzes thio-disulfide exchange reactions, has been found on the
      cell-surface membrane. We hypothesized that cell-surface PDI reacts with NO,
      catalyzes S-nitrosation reactions, and facilitates NO transfer from the
      extracellular to intracellular compartment. We observed that PDI catalyzes the S
      nitrosothiol-dependent oxidation of the heme group of myoglobin (15-fold increase
      in the rate of oxidation compared with control), and that NO reduces the activity
      of PDI by 73.1 +/- 21.8% (P < 0.005). To assess the role of PDI in the cellular
      action of NO, we inhibited human erythroleukemia (HEL) cell-surface PDI
      expression using an antisense phosphorothioate oligodeoxynucleotide directed
      against PDI mRNA. This oligodeoxynucleotide decreased cell-surface PDI content by
      74.1 +/- 9.3% and PDI folding activity by 46.6 +/- 3.5% compared with untreated
      or "scrambled" phosphorothioate oligodeoxynucleotide-treated cells (P < 0.0001).
      This decrease in cell-surface PDI was associated with a significant decrease in
      cyclic guanosine monophosphate (cGMP) generation after S-nitrosothiol exposure
      (65.4 +/- 26.7% reduction compared with control; P < 0.05), with no effect on
      cyclic adenosine monophosphate (cAMP) generation after prostaglandin E1 exposure.
      These data demonstrate that the cellular entry of NO involves a transnitrosation
      mechanism catalyzed by cell-surface PDI. These observations suggest a unique
      mechanism by which extracellular NO gains access to the intracellular
      environment.

PMID- 9927501
TI  - Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric
      oxide synthase by estrogen.
AB  - Estrogen is an important vasoprotective molecule that causes the rapid dilation
      of blood vessels by activating endothelial nitric oxide synthase (eNOS) through
      an unknown mechanism. In studies of intact ovine endothelial cells, 17beta
      estradiol (E2) caused acute (five-minute) activation of eNOS that was unaffected
      by actinomycin D but was fully inhibited by concomitant acute treatment with
      specific estrogen receptor (ER) antagonists. Overexpression of the known
      transcription factor ERalpha led to marked enhancement of the acute response to
      E2, and this was blocked by ER antagonists, was specific to E2, and required the
      ERalpha hormone-binding domain. In addition, the acute response of eNOS to E2 was
      reconstituted in COS-7 cells cotransfected with wild-type ERalpha and eNOS, but
      not by transfection with eNOS alone. Furthermore, the inhibition of tyrosine
      kinases or mitogen-activated protein (MAP) kinase kinase prevented the activation
      of eNOS by E2, and E2 caused rapid ER-dependent activation of MAP kinase. These
      findings demonstrate that the short-term effects of estrogen central to
      cardiovascular physiology are mediated by ERalpha functioning in a novel,
      nongenomic manner to activate eNOS via MAP kinase-dependent mechanisms.

PMID- 9927503
TI  - Lipid infusion lowers sympathetic nervous activity and leads to increased beta
      cell responsiveness to glucose.
AB  - We investigated the possible involvement of the autonomic nervous system in the
      effect of a long-term elevation of plasma free fatty acid (FFA) concentration on
      glucose-induced insulin secretion (GIIS) in rats. Rats were infused with an
      emulsion of triglycerides (Intralipid) for 48 hours (IL rats). This resulted in a
      twofold increase in plasma FFA concentration. At the end of infusion, GIIS as
      reflected in the insulinogenic index (DeltaI/DeltaG) was 2.5-fold greater in IL
      rats compared with control saline-infused rats. The ratio of sympathetic to
      parasympathetic nervous activities was sharply decreased in IL rats relative to
      controls. GIIS was studied in the presence of increasing amounts of alpha- and
      beta-adrenoreceptor agonists and antagonists. The lowest concentrations of the
      alpha2A-adrenoreceptor agonist oxymetazoline, which were ineffective in control
      rats, reduced GIIS in IL rats. At the dose of 0.3 pmol/kg, GIIS became similar in
      IL and control rats. The use of beta-adrenoreceptor agonist (isoproterenol) or
      antagonist (propranolol) did not result in a significant alteration in GIIS in
      both groups. GIIS remained as high in IL vagotomized rats as in intact IL rats,
      indicating that changes in parasympathetic tone were of minor importance.
      Altogether, the data show that lipid infusion provokes beta-cell
      hyperresponsiveness in vivo, at least in part through changes in alpha2
      adrenergic innervation.

PMID- 9927502
TI  - Leukocyte infection by the granulocytic ehrlichiosis agent is linked to
      expression of a selectin ligand.
AB  - Human granulocytic ehrlichiosis (HGE) is an emerging tickborne illness caused by
      an intracellular bacterium that infects neutrophils. Cells susceptible to HGE
      express sialylated Lewis x (CD15s), a ligand for cell selectins. We demonstrate
      that adhesion of HGE to both HL60 cells and normal bone marrow cells directly
      correlates with their CD15s expression. HGE infection of HL60 cells, bone marrow
      progenitors, granulocytes, and monocytes was blocked by monoclonal antibodies
      against CD15s. However, these antibodies did not inhibit HGE binding, and anti
      CD15s was capable of inhibiting the growth of HGE after its entry into the target
      cell. In contrast, neuraminidase treatment of HL60 cells prevented both HGE
      binding and infection. A cloned cell line (HL60-A2), derived from HL60 cells and
      resistant to HGE, was deficient in the expression of alpha-(1,
      3)fucosyltransferase (Fuc-TVII), an enzyme known to be required for CD15s
      biosynthesis. Less than 1% of HL60-A2 cells expressed CD15s, and only these rare
      CD15s-expressing cells bound HGE and became infected. After transfection with Fuc
      TVII, cells regained CD15s expression, as well as their ability to bind HGE and
      become infected. Thus, CD15s expression is highly correlated with susceptibility
      to HGE, and it, and/or a closely related sialylated and alpha-(1,3) fucosylated
      molecule, plays a key role in HGE infection, an observation that may help explain
      the organism's tropism for leukocytes.

PMID- 9927504
TI  - The relationship of hydroxyeicosatetraenoic acids and F2-isoprostanes to plaque
      instability in human carotid atherosclerosis.
AB  - Evidence for increased oxidant stress has been reported in human atherosclerosis.
      However, no information is available about the importance of in situ oxidant
      stress in relation to plaque stability. This information is relevant because the
      morbidity and mortality of atherosclerosis are essentially the consequences of
      acute ischemic syndromes due to unstable plaques. We studied 30 carotid
      atherosclerotic plaques retrieved by endarterectomy from 18 asymptomatic (stable
      plaques) and 12 symptomatic patients (unstable plaques). Four normal arteries
      served as controls. After lipid extraction and ester hydrolysis, quantitation of
      different indices of oxidant stress were analyzed, including
      hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatetraenoic acids (EETs),
      ketoeicosatetraenoic acids (oxo-ETEs), and F2-isoprostanes using online reverse
      phase high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS).
      All measurements were carried out in a strictly double-blind procedure. We found
      elevated levels of the different compounds in atherosclerotic plaques. Levels of
      HETEs were 24 times higher than EETs, oxo-ETEs, or F2-isoprostanes. Levels of
      HETEs, but not those of EETs, oxo-ETEs or F2-isoprostanes, were significantly
      elevated in plaques retrieved from symptomatic patients compared with those
      retrieved from asymptomatic patients (1, 738 +/- 274 vs. 1,002 +/- 107 pmol/
      micromol lipid phosphorous, respectively; P < 0.01). One monooxygenated
      arachidonate species, 9-HETE, which cannot be derived from known enzymatic
      reactions, was the most abundant and significant compound observed in plaques,
      suggesting that nonenzymatic lipid peroxidation predominates in advanced
      atherosclerosis and may promote plaque instability.

PMID- 9927505
TI  - Glucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3).
AB  - In the absence of exogenous glucocorticoids, decreasing media pH (from 7.4 to
      6.8) for 24 hours increased the Na+/H+ exchanger 3 (NHE3) activity in opossum
      kidney (OKP) cells. 10(-7) M and 10(-8) M hydrocortisone increased NHE3 activity,
      and in their presence, acid incubation further increased NHE3 activity.
      Hydrocortisone (10(-9) M) had no effect on NHE3 activity, but in its presence,
      the effect of acid incubation on NHE3 activity increased twofold. Aldosterone
      (10(-8) M) had no effect. In the absence of hydrocortisone, acid incubation
      increased NHE3 protein abundance by 47%; in the presence of 10(-9) M
      hydrocortisone, acid incubation increased NHE3 protein abundance by 132%. The
      increase in NHE3 protein abundance was dependent on protein synthesis. However,
      10(-9) M hydrocortisone did not modify the effect of acid incubation to cause a
      twofold increase in NHE3 mRNA abundance. In the absence of protein synthesis, 10(
      9) M hydrocortisone did potentiate an effect of acid on NHE3 activity, which was
      due to trafficking of NHE3 to the apical membrane. These results suggest that
      glucocorticoids and acid interact synergistically at the level of NHE3
      translation and trafficking.

PMID- 9927506
TI  - Chemokines and the homing of dendritic cells to the T cell areas of lymphoid
      organs.

PMID- 9927507
TI  - Mice lacking expression of secondary lymphoid organ chemokine have defects in
      lymphocyte homing and dendritic cell localization.
AB  - Secondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules
      and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T
      cells. In mice homozygous for the paucity of lymph node T cell (plt) mutation,
      naive T cells fail to home to LNs or the lymphoid regions of spleen. Here we
      demonstrate that expression of SLC is undetectable in plt mice. In addition to
      the defect in T cell homing, we demonstrate that dendritic cells (DCs) fail to
      accumulate in spleen and LN T cell zones of plt mice. DC migration to LNs after
      contact sensitization is also substantially reduced. The physiologic significance
      of these abnormalities in plt mice is indicated by a markedly increased
      sensitivity to infection with murine hepatitis virus. The plt mutation maps to
      the SLC locus; however, the sequence of SLC introns and exons in plt mice is
      normal. These findings suggest that the abnormalities in plt mice are due to a
      genetic defect in the expression of SLC and that SLC mediates the entry of naive
      T cells and antigen-stimulated DCs into the T cell zones of secondary lymphoid
      organs.

PMID- 9927508
TI  - Effects of complementarity determining region mutations on the affinity of an
      alpha/beta T cell receptor: measuring the energy associated with CD4/CD8
      repertoire skewing.
AB  - It has been proposed that the generally low affinities of T cell receptors (TCRs)
      for their peptide-major histocompatibility complex (pMHC) ligands (Kd
      approximately 10(-4) to 10(-7) M) are the result of biological selection rather
      than an intrinsic affinity limitation imposed by the TCR framework. Using a
      soluble version of the 2C TCR, we have used complementarity determining region
      (CDR)-directed mutagenesis to investigate whether the affinity of this receptor
      for its allogeneic pMHC ligand can be improved upon. We report that several
      mutants at positions lying within CDR3alpha and CDR2beta showed increased
      affinities for pMHC compared with the wild-type receptor. Additionally, we have
      investigated whether Valpha mutations that have been implicated in the phenomenon
      of CD8(+) repertoire skewing achieve this skewing by means of generalized
      increases in affinity for MHC-I molecules. Two mutants (S27F and S51P), which
      each promote skewing toward a CD8(+) phenotype, exhibited significantly reduced
      affinity for pMHC-I, consistent with a quantitative-instructional model of
      CD4/CD8 lineage commitment. This model predicts that CD8 is downregulated on
      thymocytes that have TCR-ligand interactions above a minimal energy threshold.
      Together, the results (a) demonstrate that engineering higher affinity TCRs is
      feasible, and (b) provide TCR-pMHC energy values associated with CD4/CD8
      repertoire skewing.

PMID- 9927509
TI  - Severe attenuation of the B cell immune response in Msh2-deficient mice.
AB  - Recently, results obtained from mice with targeted inactivations of
      postreplication DNA mismatch repair (MMR) genes have been interpreted to
      demonstrate a direct role for MMR in antibody variable (V) gene hypermutation.
      Here we show that mice that do not express the MMR factor Msh2 have wide-ranging
      defects in antigen-driven B cell responses. These include lack of progression of
      the germinal center (GC) reaction associated with increased intra-GC apoptosis,
      severely diminished antigen-specific immunoglobulin G responses, and near absence
      of anamnestic responses. Mice heterozygous for the Msh2 deficiency display an
      "intermediate" phenotype in these regards, suggesting that normal levels of Msh2
      expression are critical for the B cell response. Interpretation of the impact of
      an MMR deficiency on the mechanism of V gene somatic hypermutation could be
      easily confounded by these perturbations.

PMID- 9927510
TI  - The murine nonclassical class I major histocompatibility complex-like CD1.1
      molecule protects target cells from lymphokine-activated killer cell cytolysis.
AB  - Classical class I major histocompatibility complex (MHC) molecules, as well as
      the nonclassical class I histocompatibility leukocyte antigen (HLA)-E molecule,
      can negatively regulate natural killer (NK) cell cytotoxicity through engagement
      of NK inhibitory receptors. We show that expression of murine (m)CD1.1, a
      nonpolymorphic nonclassical MHC class I-like molecule encoded outside the MHC,
      protects NK-sensitive RMA/S target cells from adherent lymphokine-activated
      killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant
      interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of
      relevant A-LAK population(s) or modulation of A-LAK receptor expression. Murine
      CD1. 1 conferred protection from lysis by rIL-2-activated spleen cells of
      recombination activating gene (Rag)-1(-/-) mice, which lack B and T cells,
      demonstrating that mCD1.1 can protect RMA/S cells from lysis by NK cells. An
      antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1
      transfectants, indicating that cell surface mCD1.1 can confer protection from
      lysis; therefore, mCD1.1 possibly acts through interaction with an NK inhibitory
      receptor. CD1.1 is by far the most divergent class I molecule capable of
      regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells
      resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of
      mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that mCD1.1 may
      be a ligand for a conserved NK inhibitory receptor.

PMID- 9927511
TI  - Mouse Ly-49D recognizes H-2Dd and activates natural killer cell cytotoxicity.
AB  - Although activation of natural killer (NK) cytotoxicity is generally inhibited by
      target major histocompatibility complex (MHC) class I expression, subtle features
      of NK allorecognition suggest that NK cells possess receptors that are activated
      by target MHC I. The mouse Ly-49D receptor has been shown to activate NK
      cytotoxicity, although recognition of MHC class I has not been demonstrated
      previously. To define Ly-49D-ligand interactions, we transfected the mouse Ly-49D
      receptor into the rat NK line, RNK-16 (RNK.mLy-49D). As expected, anti- Ly-49D
      monoclonal antibody 12A8 specifically stimulated redirected lysis of the Fc
      receptor- bearing rat target YB2/0 by RNK.mLy-49D transfectants. RNK.mLy-49D
      effectors were tested against YB2/0 targets transfected with the mouse MHC I
      alleles H-2Dd, Db, Kk, or Kb. RNK.mLy-49D cells lysed YB2/0.Dd targets more
      efficiently than untransfected YB2/0 or YB2/0 transfected with Db, Kk, or Kb.
      This augmented lysis of H-2Dd targets was specifically inhibited by F(ab')2 anti
      Ly-49D (12A8) and F(ab')2 anti-H-2Dd (34-5-8S). RNK.mLy-49D effectors were also
      able to specifically lyse Concanavalin A blasts isolated from H-2(d) mice
      (BALB/c, B10.D2, and DBA/2) but not from H-2(b) or H-2(k) mice. These experiments
      show that the activating receptor Ly-49D specifically interacts with the MHC I
      antigen, H-2Dd, demonstrating the existence of alloactivating receptors on murine
      NK cells.

PMID- 9927512
TI  - Growth inhibition and apoptosis due to restoration of E2A activity in T cell
      acute lymphoblastic leukemia cells.
AB  - Two models have been proposed for the molecular mechanism by which the Tal1
      oncogene causes T cell acute lymphoblastic leukemia (T-ALL). The activation model
      suggests that Tal1 as heterodimers with the E2A transcription factor activates
      the expression of oncogenes. The inhibition model postulates that Tal1 interferes
      with the tumor-suppressing function of E2A. In the Jurkat T cell line, originally
      derived from a patient with T-ALL, Tal1 is complexed with E2A proteins and the
      transcriptional activity of E2A is very low. When E2A activity was restored by
      expressing an E2A-Tal1 fusion protein, E-T/2, the Jurkat cells underwent growth
      arrest and subsequently apoptosis, thus supporting the inhibition model and
      suggesting that E2A loss may contribute to leukemic progression.

PMID- 9927514
TI  - Type I interferons keep activated T cells alive.
AB  - Antigen injection into animals causes antigen-specific T cells to become
      activated and, rapidly thereafter, die. This antigen-induced death is inhibited
      by inflammation. To find out how inflammation has this effect, various cytokines
      were tested for their ability to interfere with the rapid death of activated T
      cells. T cells were activated in vivo, isolated, and cultured with the test
      reagents. Two groups of cytokines were active, members of the interleukin 2
      family and the interferons (IFNs) alpha and beta. This activity of IFN-alpha/beta
      has not been described previously. It was due to direct effects of the IFNs on
      the T cells and was not mediated by induction of a second cytokine such as
      interleukin 15. IFN-gamma did not slow the death of activated T cells, and
      therefore the activity of IFN-alpha/beta was not mediated only by activation of
      Stat 1, a protein that is affected by both classes of IFN. IFN-alpha/beta did not
      raise the levels of Bcl-2 or Bcl-XL in T cells. Therefore, their activity was
      distinct from that of members of the interleukin 2 family or CD28 engagement.
      Since IFN-alpha/beta are very efficiently generated in response to viral and
      bacterial infections, these molecules may be among the signals that the immune
      system uses to prevent activated T cell death during infections.

PMID- 9927513
TI  - Molecular requirements for T cell recognition by a major histocompatibility
      complex class II-restricted T cell receptor: the involvement of the fourth
      hypervariable loop of the Valpha domain.
AB  - The role of two central residues (K68, E69) of the fourth hypervariable loop of
      the Valpha domain (HV4alpha) in antigen recognition by an MHC class II-restricted
      T cell receptor (TCR) has been analyzed. The TCR recognizes the NH2-terminal
      peptide of myelin basic protein (Ac1-11, acetylated at NH2 terminus) associated
      with the class II MHC molecule I-Au. Lysine 68 (K68) and glutamic acid 69 (E69)
      of HV4alpha have been mutated both individually and simultaneously to alanine
      (K68A, E69A). The responsiveness of transfectants bearing wild-type and mutated
      TCRs to Ac1-11-I-Au complexes has been analyzed in the presence and absence of
      expression of the coreceptor CD4. The data demonstrate that in the absence of CD4
      expression, K68 plays a central role in antigen responsiveness. In contrast, the
      effect of mutating E69 to alanine is less marked. CD4 coexpression can partially
      compensate for the loss of activity of the K68A mutant transfectants, resulting
      in responses that, relative to those of the wild-type transfectants, are highly
      sensitive to anti-CD4 antibody blockade. The observations support models of T
      cell activation in which both the affinity of the TCR for cognate ligand and the
      involvement of coreceptors determine the outcome of the T cell-antigen-presenting
      cell interaction.

PMID- 9927515
TI  - Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen
      and endogenous autoantigen determine the specificities of the induced
      autoantibodies.
AB  - Anti-Ro60 autoantibodies are found in a variety of autoimmune disorders including
      systemic lupus erythematosus (SLE), Sjogren's syndrome, primary biliary
      cirrhosis, and active hepatitis. They are the most prevalent autoantibodies in
      normal individuals and in asymptomatic mothers of infants afflicted with neonatal
      lupus. In the present study, immune responses to recombinant human Ro60 (rhRo60)
      and recombinant mouse Ro60 (rmRo60) and selected Ro60 peptides in non-SLE-prone
      mice were investigated. Multiple T and B cell epitopes were identified in Ro60.
      Immunizations with either xenogeneic or autologous Ro60 induced autoantibodies to
      a diverse group of autoantigens. In addition to La and Ro52, proteins in the
      small nuclear ribonucleoprotein (snRNP) particles such as SmA, SmB, SmD, and 70
      kD U1-RNP were unexpectedly identified as targeted antigens. In the studies
      involving synthetic Ro60 peptides, both human and mouse Ro60316-335 peptides,
      which differ in three amino acids, were found to contain dominant cross-reactive
      T cell determinants. Immunizations with these peptides induced autoantibodies to
      Ro60, La, SmD, and 70-kD U1-RNP without autoantibodies to Ro52, SmA, or SmB. With
      human Ro60316-335 as the immunogen, additional autoantibodies reactive with the
      Golgi complex were found. In contrast to the immunodominance of both human and
      mouse Ro60316-335 peptides, the T cell determinant in human Ro60441-465 was
      dominant, whereas that in the mouse peptide was cryptic. Immunization with human
      Ro60441-465 induced primarily anti-peptide Abs. Mouse Ro60441-465 failed to
      induce an antibody response. These results show that both the nature of the
      immunogen and the immunogenicity of the related endogenous antigen are important
      in determining the specificities of the autoantibodies generated. They have
      significant implications for proposed mechanisms on the generation of complex
      patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

PMID- 9927517
TI  - Natural killer cells determine development of allergen-induced eosinophilic
      airway inflammation in mice.
AB  - The earliest contact between antigen and the innate immune system is thought to
      direct the subsequent antigen-specific T cell response. We hypothesized that
      cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T
      cells (NKT cells), and gamma/delta T cells, may regulate the development of
      allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK
      cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+)
      T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and
      IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma.
      Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and
      the number of IL-4 and interferon gamma-producing splenic cells were diminished
      in mice depleted of NK1.1(+) cells before the priming regime. Depletion of
      NK1.1(+) cells during the challenge period only did not influence pulmonary
      eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with
      normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE
      levels not different from those observed in wild-type mice. Mice deficient in
      gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this
      model. Taken together, these findings suggest a critical role of NK cells, but
      not of NKT cells, for the development of allergen-induced airway inflammation,
      and that this effect of NK cells is exerted during the immunization. If
      translatable to humans, these data suggest that NK cells may be critically
      important for deciding whether allergic eosinophilic airway disease will develop.
      These observations are also compatible with a pathogenic role for the increased
      NK cell activity observed in human asthma.

PMID- 9927516
TI  - Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1
      and beta2 chain expression.
AB  - Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to
      induce T helper cell type 2 (Th2) responses in systemic and mucosal tissues. We
      report that CT inhibits the production of interleukin (IL)-12, a major Th2
      counterregulatory cytokine. IL-12 p70 production by stimulated human monocytes
      was inhibited by CT in a dose-dependent manner. This suppression occurred at the
      level of gene transcription, was maximal at low concentrations of CT, and was
      dependent on the A subunit of the toxin, since purified CT B subunit had minimal
      effect. CT also inhibited the production of IL-12 p70 by monocyte-derived
      dendritic cells, as well as the production of tumor necrosis factor alpha, but
      not IL-10, IL-6, or transforming growth factor (TGF)-beta1, by stimulated
      monocytes. The effects of CT were not due to autocrine production of IL-10, TGF
      beta1, or prostaglandin E2. CT inhibited the production of IFN-gamma by anti-CD3
      stimulated human peripheral blood mononuclear cell, due in part to suppression of
      IL-12 production, but also to the inhibition of expression of the beta1 and beta2
      chains of the IL-12 receptor on T cells. In vivo, mice given CT before systemic
      challenge with lipopolysaccharide had markedly reduced serum levels of IL-12 p40
      and interferon gamma. These data demonstrate two novel mechanisms by which CT can
      inhibit Th1 immune responses, and help explain the ability of mucosally
      administered CT to enhance Th2-dependent immune responses.

PMID- 9927518
TI  - The common cytokine receptor gamma chain and the pre-T cell receptor provide
      independent but critically overlapping signals in early alpha/beta T cell
      development.
AB  - Intracellular signals emanating from cytokine and antigen receptors are
      integrated during the process of intrathymic development. Still, the relative
      contributions of cytokine receptor signaling to pre-T cell receptor (TCR) and TCR
      mediated differentiation remain undefined. Interleukin (IL)-7 interactions with
      its cognate receptor complex (IL-7Ralpha coupled to the common cytokine receptor
      gamma chain, gammac) play a dominant role in early thymopoiesis. However,
      alpha/beta T cell development in IL-7-, IL-7Ralpha-, and gammac-deficient mice is
      only partially compromised, suggesting that additional pathways can rescue
      alpha/beta T lineage cells in these mice. We have investigated the potential
      interdependence of gammac- and pre-TCR-dependent pathways during intrathymic
      alpha/beta T cell differentiation. We demonstrate that gammac-dependent cytokines
      do not appear to be required for normal pre-TCR function, and that the rate
      limiting step in alpha/beta T cell development in gammac- mice does not involve
      TCR-beta chain rearrangements, but rather results from poor maintenance of early
      thymocytes. Moreover, mice double mutant for both gammac and pre-Talpha show
      vastly reduced thymic cellularity and a complete arrest of thymocyte
      differentiation at the CD44(+)CD25(+) cell stage. These observations demonstrate
      that the pre-TCR provides the gammac-independent signal which allows alpha/beta T
      cell development in gammac- mice. Thus, a series of overlapping signals derived
      from cytokine and T cell receptors guide the process of alpha/beta thymocyte
      development.

PMID- 9927520
TI  - CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of
      distinct T helper cells in vivo.
AB  - Cells of the dendritic family display some unique properties that confer to them
      the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two
      subclasses of dendritic cells (DCs) have been described that differ by their
      CD8alpha expression and their localization in lymphoid organs. The physiologic
      function of both cell populations remains obscure. Studies conducted in vitro
      have suggested that CD8alpha+ DCs could play a role in the regulation of immune
      responses, whereas conventional CD8alpha- DCs would be more stimulatory. We
      report here that both subclasses of DCs efficiently prime antigen-specific T
      cells in vivo, and direct the development of distinct T helper (Th) populations.
      Antigen-pulsed CD8alpha+ and CD8alpha- DCs are separated after overnight culture
      in recombinant granulocyte/macrophage colony-stimulating factor and injected into
      the footpads of syngeneic mice. Administration of CD8alpha- DCs induces a Th2
      type response, whereas injection of CD8alpha+ DCs leads to Th1 differentiation.
      We further show that interleukin 12 plays a critical role in Th1 development by
      CD8alpha+ DCs. These findings suggest that the nature of the DC that presents the
      antigen to naive T cells may dictate the class selection of the adaptative immune
      response.

PMID- 9927519
TI  - Bad can act as a key regulator of T cell apoptosis and T cell development.
AB  - Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show
      that Bad expression levels are greatly increased in thymocytes during apoptosis.
      We generated bad transgenic mice to study the action of upregulated Bad
      expression on T cell apoptosis. The T cells from these mice are highly sensitive
      to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly
      depleted and the processes of T cell development and selection are perturbed. We
      show that the proapoptotic function of Bad in primary T cells is regulated by Akt
      kinase and that Bad overexpression enhances both cell cycle progression and
      interleukin 2 production after T cell activation. These data suggest that Bad can
      act as a key regulator of T cell apoptosis and that this is a consequence of its
      upregulation after exposure to death stimuli.

PMID- 9927521
TI  - Antigen-pulsed CD8alpha+ dendritic cells generate an immune response after
      subcutaneous injection without homing to the draining lymph node.
AB  - Two subsets of murine splenic dendritic cells, derived from distinct precursors,
      can be distinguished by surface expression of CD8alpha homodimers. The functions
      of the two subsets remain controversial, although it has been suggested that the
      lymphoid-derived (CD8alpha+) subset induces tolerance, whereas the myeloid
      derived (CD8alpha-) subset has been shown to prime naive T cells and to generate
      memory responses. To study their capacity to prime or tolerize naive CD4(+) T
      cells in vivo, purified CD8alpha+ or CD8alpha- dendritic cells were injected
      subcutaneously into normal mice. In contrast to CD8alpha- dendritic cells, the
      CD8alpha+ fraction failed to traffic to the draining lymph node and did not
      generate responses to intravenous peptide. However, after in vitro pulsing with
      peptide, strong in vivo T cell responses to purified CD8alpha+ dendritic cells
      could be detected. Such responses may have been initiated via transfer of peptide
      major histocompatibility complex complexes to migratory host CD8alpha- dendritic
      cells after injection. These data suggest that correlation of T helper cell type
      1 (Th1) and Th2 priming with injection of CD8alpha+ and CD8alpha- dendritic
      cells, respectively, may not result from direct T cell activation by lymphoid
      versus myeloid dendritic cells, but rather from indirect modification of the
      response to immunogenic CD8alpha- dendritic cells by CD8alpha+ dendritic cells.

PMID- 9927523
TI  - Call for papers 

PMID- 9927525
TI  - Phonological recoding and orthographic learning: A direct test of the self
      teaching hypothesis.
AB  - According to the self-teaching hypothesis (Share, 1995), word-specific
      orthographic representations are acquired primarily as a result of the self
      teaching opportunities provided by the phonological recoding of novel letter
      strings. This hypothesis was tested by asking normal second graders to read aloud
      short texts containing embedded pseudoword targets. Three days later, target
      spellings were correctly identified more often, named more quickly, and spelled
      more accurately than alternate homophonic spellings. Experiment 2 examined
      whether this rapid orthographic learning can be attributed to mere visual
      exposure to target strings. It was found that viewing the target letter strings
      under conditions designed to minimize phonological processing significantly
      attenuated orthographic learning. Experiment 3 went on to show that this reduced
      orthographic learning was not attributable to alternative nonphonological factors
      (brief exposure durations or decontextualized presentation). The results of a
      fourth experiment suggested that the contribution of pure visual exposure to
      orthographic learning is marginal. It was concluded that phonological recoding is
      critical to the acquisition of word-specific orthographic representations as
      proposed by the self-teaching hypothesis.

PMID- 9927522
TI  - C-reactive protein: a physiological activator of interleukin 6 receptor shedding.
AB  - The soluble interleukin 6 receptor (sIL-6R) circulates at elevated levels in
      various diseases. This suggests that inflammatory mediators control sIL-6R
      release. Through examination of human neutrophils, it was found that the acute
      phase reactant C-reactive protein (CRP) activates a threefold increase in sIL-6R
      production. Maximal release occurred after 30-60 min exposure to CRP (50
      micrograms/ml), and was mimicked by peptides corresponding to amino acid residues
      174- 185 and 201-206 of native CRP. A third peptide fragment (77-82) had no
      effect. Differential mRNA splicing did not account for the CRP-mediated release
      of sIL-6R, since this isoform was not detected in conditioned media. Furthermore,
      stimulation of neutrophils with CRP or with peptides 174-185 or 201-206 promoted
      a loss of membrane-bound IL-6R, suggesting release by proteolytic shedding. The
      metalloprotease inhibitor TAPI had only a marginal effect on CRP-mediated sIL-6R
      release, suggesting that shedding occurs via a mechanism distinct from that
      previously reported. It well established that IL-6 stimulates the acute phase
      expression of CRP. Our current findings demonstrate a novel relationship between
      these two mediators, since CRP may affect IL-6-mediated inflammatory events by
      enabling formation of the sIL-6R/IL-6 complex.

PMID- 9927527
TI  - Volume 151, Number 2 (1998): Cesario V. Borlongan, Samuel Saporta, and Paul R.
      Sanberg, "Intrastriatal Transplantation of Rat Adrenal Chromaffin Cells Seeded on
      Microcarrier Beads Promote Long-Term Functional Recovery in Hemiparkinsonian
      Rats," pp. 203-214:

PMID- 9927524
TI  - Varieties of developmental reading disorder: genetic and environmental
      influences.
AB  - There is widespread support for the notion that subgroups of dyslexics can be
      identified who differ in their reading profiles: Developmental phonological
      dyslexia is characterized by poor nonword reading, while developmental surface
      dyslexia is distinguished by a particular difficulty in reading irregular words.
      However, there is much less agreement about how these subtypes, and particularly
      the surface dyslexic pattern, are to be accounted for within theoretical models
      of the reading system. To assist in addressing this issue, the heritability of
      reading deficits in dyslexic subtypes was examined using a twin sample. Subjects'
      scores on (a) an exception word reading task and (b) a nonword reading task were
      used to create a subtype dimension, and surface and phonological dyslexic
      subgroups were selected from the ends of this distribution. Reading deficits were
      found to be significantly heritable in both subgroups. However, the genetic
      contribution to the group reading deficit was much greater in the phonological
      dyslexics than in the surface dyslexics. The finding of differential genetic
      etiology across subtypes suggests that there is at least partial independence in
      the development of the cognitive processes involved in reading exception words
      and nonwords. Also, the results support accounts of surface dyslexia which
      emphasize a strong environmental contribution.

PMID- 9927528
TI  - Volume 147, Number 2 (1997): Agneta Othberg, Marcus Keep, Patrik Brundin, and
      Olle Lindvall, "Tirilazad Mesylate Improves Survival of Rat and Human Embryonic
      Mesencephalic Neurons in Vitro," pp. 498-502:

PMID- 9927526
TI  - Phonemes, rhymes, and intelligence as predictors of children's responsiveness to
      remedial reading instruction: evidence from a longitudinal intervention study.
AB  - We present an analysis of data from a longitudinal intervention study with 7-year
      old poor readers (Hatcher, Hulme, & Ellis, 1994). A battery of cognitive and
      phonological tasks administered before the intervention began revealed five
      separate factors: Phoneme Manipulation, Rhyme, Verbal Ability, Nonverbal Ability
      and Phonological Memory. We assessed the extent to which these factors were
      predictive of children's responsiveness to the teaching interventions they
      received. For reading accuracy, Verbal Ability, Nonverbal Ability, Phonological
      Memory, and Rhyme made no significant contribution to predicting responsiveness
      to teaching, while Phoneme Manipulation was a very strong predictor. However for
      reading comprehension, Verbal ability (but not nonverbal ability) made an
      additional unique contribution to predicting responsiveness to teaching. The
      results are discussed in the context of current theories of the role of
      intelligence and phonological skills in learning to read.

PMID- 9927529
TI  - Reinventing the academic medical center.

PMID- 9927530
TI  - Anti-TNF antibody modulates cytokine and MHC expression in cardiac allografts.
AB  - Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine evoked in
      response to alloantigen stimulation and may be involved in lymphocyte activation,
      adhesion molecule expression, and regulation of MHC class II antigens. Anti-TNF
      treatment prolongs cardiac allograft survival. We investigated the role of anti
      TNF in the regulation of MHC class II antigens and cytokine mRNA expression of
      TNF, interferon-gamma (IFN), IL-2, IL-4, and IL-10 in cardiac allografts to
      elucidate its immunological mechanism. These in vivo studies were conducted using
      a rat MHC mismatch Brown-Norway to Lewis (BN to LEW) heterotopic cardiac
      transplant model. In control untreated rats, allografts were rejected at 6.8 +/-
      0.6 days. Allograft survival was significantly prolonged to 12.7 +/- 1.4 days
      with anti-TNF treatment. MHC class II expression, analyzed by indirect
      immunofluorescence cytometry, demonstrated that MHC class II-positive cells
      increased by 25% in spleens of untreated allografted rats compared to naive rats,
      while anti-TNF-treated allografted rats had a similar percentage of MHC II cells
      as naives. Further, naive, untransplanted rats and both anti-TNF and untreated,
      transplanted rats had heart and spleens harvested on Day 5 post-transplant.
      Cytokine mRNA expression was determined by semiquantitative RT-PCR. In heart and
      spleen cells from naives, TNF mRNA expression was undetectable or very weak.
      However, in rejecting allografts and spleen cells from untreated recipients, TNF
      expression was remarkably increased, while anti-TNF attenuated this TNF
      expression in both heart graft and spleen cells. Furthermore, IL-2, IL-10, and
      IFN expression were absent in naive hearts. However, in untreated allografts IL
      2, IL-10, and IFN were strongly expressed, which was markedly decreased after
      anti-TNF treatment. Finally, IL-4 expression was found equally in naive hearts,
      untreated allografts, and anti-TNF-treated allografts. These results suggest that
      anti-TNF antibody treatment may not only neutralize TNF activity but also play a
      role in altering cytokine mRNA expression and MHC class II expression.

PMID- 9927531
TI  - Hepato-splanchnic blood flow and oxygen extraction capabilities during
      experimental tamponade: effects of endotoxin.
AB  - We studied the hepato-splanchnic vascular response and changes in O2 extraction
      capabilities to a reduction in blood flow following endotoxemia. Fourteen
      anesthetized and mechanically ventilated dogs were divided into two groups of
      seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as
      a control. After initial fluid resuscitation following endotoxic shock, regional
      blood flow estimated by an ultrasonic technique increased similarly in the
      hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow
      estimated by a laser Doppler technique was lower in the liver than in the
      intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin
      treated animals had greater whole body and regional critical O2 delivery
      (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction
      ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit
      was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply
      dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3
      +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and
      endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg.
      min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid
      resuscitated endotoxic shock in dogs is characterized by blood flow
      redistribution within the liver and intestine. Microvascular depression may be
      more severe in the liver than in the intestinal mucosa, although the whole body,
      the liver, and the intestine became O2 supply-dependent simultaneously.

PMID- 9927532
TI  - A regenerative change during muscle adaptation to denervation in rats.
AB  - The purpose of this study is to examine the cellular and molecular events
      coincident with muscle denervation, especially the regenerative changes seen
      following muscle denervation, the role of satellite cells in this process, and
      the possibility of apoptotic degeneration of myonuclei as a mechanism of
      myonuclei loss during muscle denervation atrophy. Myosin heavy chain (MHC)
      isoform expression during muscle denervation was examined using pyrophosphate
      acrylamide gel electrophoresis and immunohistochemistry. DNA fragmentation
      (apoptosis) in myonuclei of denervated fibers was investigated using agarose gel
      electrophoresis, the TUNEL technique and ELISA for cytoplasmic histone-associated
      DNA fragmentation. Immunohistochemistry for MyoD and BrdU was also performed.
      Following muscle denervation, embryonic MHC, which is not expressed in adult
      healthy muscles, was expressed in some denervated fibers as well as in small
      activated satellite cells; maximal expression was observed 2 to 3 weeks after
      denervation. Activation and proliferation of satellite cells were observed, while
      few typical regenerating fibers were identified. It is speculated that most
      activated satellite cells fused to the denervated maternal fibers in order to
      repair them instead of fusing to each other to form new fibers as a mechanism
      that compensates for the atrophic changes after denervation. Although DNA ladder
      formation was not observed with agarose gel electrophoresis, DNA fragmentation
      was detected by the TUNEL technique and ELISA, suggesting that apoptotic
      degeneration contributes to the loss of myonuclei associated with denervation
      atrophy.

PMID- 9927533
TI  - Selective downregulation of neutrophils by a phosphatidic acid generation
      inhibitor in a porcine sepsis model.
AB  - Effects of lisofylline (1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine), a functional
      inhibitor of phosphatidic acid (PA) generation derived from de novo synthesis, on
      neutrophil function were examined in a porcine sepsis model. Hanford minipigs (18
      25 kg) were randomly separated into six groups of six animals each: (1) saline
      control group; (2) sepsis control group, infused with Pseudomonas aeruginosa (1 x
      10(6) colony-forming units/kg/min) for 2 h; (3) lisofylline control group, given
      a 25 mg/kg bolus of lisofylline 30 min prior to time zero, followed by a
      continuous infusion of 10 mg/kg/h throughout the study; (4) lisofylline
      pretreatment sepsis group, given lisofylline 30 min prior to sepsis, (5)
      lisofylline 1-h post-treatment sepsis group, and (6) lisofylline 2-h post
      treatment sepsis group. All animals were studied for 6 h. Neutrophils were
      isolated at -0.5, 2, and 6 h. In the pretreatment and 1-h post-treatment groups,
      sepsis-induced neutrophil attachment to fibronectin was significantly attenuated.
      Sepsis-enhanced phagocytic activity was significantly reduced in the lisofylline
      pretreatment sepsis group, but not in the post-treatment groups. No treatment
      affected phorbol 12-myristate 13-acetate-induced chemiluminescence and basal
      filamentous actin content, which increased in sepsis, and cap formation, which
      declined in sepsis. Sepsis caused neutropenia, pretreatment produced
      neutrophilia, and 1-h post-treatment caused the neutropenia to recover to control
      levels. Interestingly, toward the end of the 6-h period, the neutrophil count was
      higher in the lisofylline control group than in the saline control groups. Thus,
      the inhibition of PA generation from de novo synthesis during sepsis not only can
      selectively downregulate some neutrophil functions but can also reverse
      neutropenia.

PMID- 9927534
TI  - Concomitant increase in neutrophil adhesion to inflammatory peritoneum and remote
      organs during peritonitis.
AB  - BACKGROUND: Neutrophils contribute to the host defense mechanism, but they can
      cause remote organ injury in peritonitis. The purpose of this study was to
      examine neutrophil adhesion to the peritoneum and remote organs simultaneously in
      peritonitis using a fluorescence microscopic method. STUDY DESIGN: Experiment 1:
      Sprague-Dawley rats (n = 16) were injected intraperitoneally (ip) with saline
      solution or 10(5), 10(7), or 10(9) Escherichia coli. Five hours after challenge,
      1 x 10(6) fluorescein-labeled neutrophils were infused. Two minutes after
      neutrophil injection, five peritoneal samples (the greater omentum, mesentery,
      parietal peritoneum, colon, and ileum), both lungs, the liver, and the right
      kidney were harvested for counting of labeled neutrophils under epifluorescent
      microscopy. Lung myeloperoxidase (MPO) activity was also determined. Experiment
      2: Rats (n = 23) were given 10(9) E. coli ip. Before challenge (0 h) or at 1, 5,
      or 10 h after challenge, labeled neutrophils were infused. Then, the labeled
      neutrophil numbers in organs and lung MPO activities were assessed as described
      for Experiment 1. Hemodynamic and arterial blood gas data were also obtained in
      another set of rats before and at 1, 5, 8 and 10 h after 10(9) E. coli ip
      challenge. RESULTS: Experiment 1: The labeled neutrophil numbers in the
      peritoneum, lungs, and kidney showed significant positive correlations with the
      injected bacterial numbers. Lung MPO also positively correlated with E. coli
      number and labeled neutrophil number in the lungs. Experiment 2: Labeled
      neutrophil numbers in the peritoneum and kidney peaked at 5 h. The pulmonary
      labeled neutrophil number rose, reaching a plateau at 5 h. No remarkable change
      was observed in the hepatic labeled neutrophil number. There was a positive
      correlation between lung MPO activity and pulmonary labeled neutrophil number.
      Hemodynamic and blood gas data reflected a hyperdynamic state. CONCLUSIONS:
      Concomitant dose-dependent increases in neutrophil adhesion in the peritoneum,
      lungs, and kidney were observed in this peritonitis model. Increased neutrophil
      adhesion was transient in the peritoneum and kidney but persistent in the lungs.
      Strategies modulating neutrophil adhesion in organs are anticipated to be useful
      for the treatment of peritonitis.

PMID- 9927536
TI  - Intestinal sleeve anastomosis: a comparative study with end-to-end anastomosis.
AB  - This study examines the utility of a sleeve anastomosis with comparison to
      conventional end to end anastomosis. Thirty New Zealand white rabbits were
      randomized to sleeve (n = 15) or end-to-end (n = 15) small bowel anastomosis.
      Five rabbits of each group were sacrificed at 3 days, 7 days, and 6 weeks.
      Anastomoses were assessed for integrity, bursting strength, and stenosis and
      examined histologically. Ten control specimens of small bowel were tested for
      bursting pressure. Three rabbits died postoperatively (1 sleeve and 2 end-to
      end). A fourth rabbit (sleeve) was sacrificed early at 3 weeks and had a total
      stenosis at the anastomosis. The remaining 26 rabbits were reoperated at the
      prescribed times. There was no evidence of infection or dehiscence in any of
      these rabbits. Both end-to-end and sleeve anastomoses were equivalent for
      bursting pressure at all times and, at 7 days and 6 weeks, were similar to
      controls. The stenotic index revealed no evidence of proximal dilation suggestive
      of obstruction in the 26 rabbits. For sleeve anastomoses the length of the
      projected bowel into the lumen persisted at the 6-week stage. Histologically
      there was good evidence of healing in both the sleeve and end-to-end anstomoses
      and the serosal surface of the sleeved bowel had epithelialized. Sleeve
      anastomosis has been demonstrated to heal well and to be as strong as
      conventional end-to-end anastomosis. Further studies are warranted to determine
      its role in intestinal anastomosis and potential as a valve.

PMID- 9927535
TI  - Phenobarbital in comparison with carbon tetrachloride and phenobarbital-induced
      cirrhosis in rat liver regeneration.
AB  - BACKGROUND: The simultaneous administration of carbon tetrachloride (CCl4) and
      phenobarbital in the rat produces one of the most common experimental models of
      liver cirrhosis. As phenobarbital also has a hepatotrophic effect, its role in
      liver regeneration following partial hepatectomy (HTX) is not elucidated.
      PURPOSE: To examine the effect of long-term administration of phenobarbital in
      liver regeneration after HTX with regard to CCl4-induced cirrhotic rat model.
      Materials and Methods. The liver regeneration following HTX in phenobarbital
      treated rats (PB rats) was compared to that seen in cirrhotic rats (LC rats),
      induced by oral gavage of CCl4 and phenobarbital, and normal rats. The effect of
      the withdrawal of phenobarbital was also examined. Liver regeneration was
      estimated 24 h after the HTX by measuring the liver weight, the DNA content in
      the liver, and [3H]thymidine incorporation into the DNA. RESULTS: Treatment with
      CCl4 and phenobarbital caused liver deformity, and the highest percentage of
      liver weight regeneration was seen in LC rats with this deformity, even though
      [3H]thymidine incorporation into the DNA was impaired in this group.
      Phenobarbital had a hepatotrophic effect, but its withdrawal caused a decrease in
      liver mass and cessation of body weight gain. The change in the DNA content 24 h
      after HTX was negative in PB rats. CONCLUSIONS: Liver regeneration could not be
      estimated using liver or body weight in the PB or LC rat model. [3H]Thymidine
      incorporation into the DNA was reliable indicator of liver regeneration in the
      different liver states during the early stage after HTX. Although the DNA content
      with respect to total liver mass was obscured due to liver inflation in PB rats,
      [3H]thymidine incorporation into the DNA between PB rats and normal rats was
      similar.

PMID- 9927537
TI  - Effects of omental wrap on performance of small-caliber high-porosity expanded
      polytetrafluoroethylene grafts.
AB  - The purpose of this study was to evaluate the effects of omental wrap on the
      performance of small-caliber expanded polytetrafluoroethylene (ePTFE) grafts,
      with a special reference to transmural capillary ingrowth. High-porosity ePTFE
      grafts with a fibril length of 60 micrometer, an internal diameter of 4 mm, and
      40 mm in length were implanted into the canine bilateral carotid arteries. The
      grafts on the right side were wrapped in an omental pedicle flap (omentum-wrap
      grafts), while those on the left were not (nonwrap grafts). The grafts were
      retrieved at intervals of 4 and 12 weeks. At 4 weeks, the patency rates of the
      omentum-wrap grafts and nonwrap grafts were almost the same (5/6 vs 6/6). At 12
      weeks, patency tended to be higher in the omentum-wrap grafts than in the nonwrap
      grafts (3/5 vs 1/5). At 4 weeks, the thrombus-free surface score (TFS) was
      significantly higher in the omentum-wrap grafts than in the nonwrap grafts (44.8%
      vs 30.2%, P < 0.05). At 12 weeks, the TFS tended to be higher in the omentum-wrap
      grafts than in the nonwrap grafts (84.6% vs 62.4%). At 4 weeks, both the
      capillary transsectional area score (CTS) and capillary density were
      significantly higher in the omentum-wrap grafts than in the nonwrap grafts (CTS,
      3.3% vs 1.1%, P < 0.05; capillary density, 196.0/mm2 vs 83.3/mm2, P < 0.05). At
      12 weeks, both CTS and capillary density tended to be higher in the omentum-wrap
      grafts than in the nonwrap grafts (CTS, 1.1% vs 0%; capillary density, 69.4/mm2
      vs 0/mm2). At 4 weeks, in the omentum-wrap grafts, extracellular matrices and
      cells in the interstices of the graft were stained with an antibody against VEGF.
      In conclusion, the omental wrap enhances transmural capillary ingrowth and
      thereby promotes endothelialization in small-caliber high-porosity ePTFE grafts.
      VEGF appears to play an active role in transmural capillary ingrowth enhanced by
      omental wrap.

PMID- 9927538
TI  - The effects of l-arginine on crypt cell hyperproliferation in colorectal cancer.
AB  - BACKGROUND: Colonic crypt cell hyperproliferation characterizes malignant and
      premalignant conditions of the colon and may be modified by dietary manipulation.
      This study compared the effect of dietary arginine supplementation on colonic
      crypt cell proliferation during the initiation and promotion stages of colorectal
      carcinogenesis. MATERIALS AND METHODS: One hundred and twenty male Wistar rats
      were divided into 5 groups of 24 animals each. Groups D, DA, FA, and LA received
      subcutaneous injections of 1, 2-dimethylhydrazine for 20 weeks. Group D received
      no arginine supplement. l-arginine was given as a 1% solution instead of drinking
      water to Group DA for 22 weeks, to Group FA for the first 10 weeks, and to Group
      LA for the last 12 weeks. EDTA animals were given subcutaneous injections of EDTA
      for 20 weeks. Colonic crypt cell proliferation was assessed in 6 animals from
      each of the five groups and in 6 normal rats not given DMH or EDTA. RESULTS: The
      BrdUrd-labeling index and proliferative zone were significantly decreased in all
      arginine groups (DA, FA, LA). The greatest reduction was evident in Group FA in
      which tumor incidence and tumor size were also significantly lowered.
      CONCLUSIONS: When given during the initiation phase of carcinogenesis l-arginine
      significantly reduced colorectal tumor production and crypt cell
      hyperproliferation.

PMID- 9927539
TI  - MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers.
AB  - BACKGROUND: The initial cleavage of collagen by collagenase represents the rate
      limiting step in the degradation of this central extracellular matrix protein.
      Chronic nonhealing ulcers, especially pressure ulcers, typically contain elevated
      levels of collagenolytic activity. However, there have been no detailed attempts
      to identify the source of these collagenases and their activity either in normal
      healing wounds or in chronic nonhealing ulcers. MATERIALS AND METHODS: Levels of
      the matrix metalloproteinases, MMP-1 and MMP-8, and the tissue inhibitor of
      matrix metalloproteinases, TIMP-1, were measured in fluids and tissues of healing
      human wounds and nonhealing ulcers by ELISA. Relative MMP-1 and MMP-8 levels were
      also analyzed by substrate preference in a functional assay. RESULTS: The
      patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct,
      with MMP-8 appearing in significantly greater amounts than MMP-1. Chronic
      nonhealing ulcers were characterized by significantly higher levels of MMP-1 and
      MMP-8, and lower levels of TIMP-1, than in healing wounds. Levels of both MMP-1
      and MMP-8 varied greatly in chronic ulcers, although MMP-8 was always the
      predominant collagenase present in these wounds. Interestingly, these
      collagenases were present almost exclusively in their inactive forms in healing
      wounds, whereas nonhealing ulcers possessed significant levels of the active
      forms of these enzymes. CONCLUSIONS: These results clearly demonstrate that the
      neutrophil-derived MMP-8 is the predominant collagenase present in normal healing
      wounds and suggest that overexpression and activation of this collagenase may be
      involved in the pathogenesis of nonhealing chronic ulcers. In addition, excessive
      collagenolytic activity in chronic ulcers is made possible, partly because of the
      reduced levels of the inhibitor, TIMP-1.

PMID- 9927541
TI  - The effect of reinnervation on force production and power output in skeletal
      muscle.
AB  - Failure to fully restore contractile function after denervation and reinnervation
      of skeletal muscle engenders significant disability in patients suffering
      peripheral nerve injuries. This work tested the hypothesis that skeletal muscle
      denervation and reinnervation result in a deficit in normalized power (W/kg),
      which exceeds the deficit in specific force (N/cm2), and that the mechanisms
      responsible for these deficits are independent. Adult Lewis rats underwent either
      transection and epineurial repair of the left peroneal nerve (denervation
      reinnervation, n = 13) or SHAM exposure of the peroneal nerve (SHAM, n = 13).
      After a 4-month recovery period, isometric force, peak power, and maximum
      sustained power output were measured in the left extensor digitorum longus (EDL)
      muscle from each animal. Isometric force measurements revealed a specific force
      deficit of 14.3% in the reinnervated muscles. Power measurements during
      isovelocity shortening contractions demonstrated a normalized peak power deficit
      of 25.8% in the reinnervated muscles, which is accounted for by decreases in both
      optimal velocity (10.5%) and average force during shortening (13.7%). Maximum
      sustained power was similar in both groups. These data support our working
      hypothesis that both whole muscle force production and power output can be
      impaired in reinnervated muscle and that the relative deficits in power output
      exceed the deficits in force production. The mechanisms responsible for the
      deficits in force production appear to be independent of those that result in
      changes in peak power output. The measurement of muscle power output may
      represent a clinically relevant variable for studies of the recovery of
      mechanical function after motor nerve injury and repair.

PMID- 9927540
TI  - The effect of nutritional and hormonal supplementation on protein synthesis
      immediately after liver transplantation.
AB  - We have previously shown that immediately after liver transplantation (LT) the
      porcine recipient exhibits elevated plasma glucagon, increased fractional
      synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural
      liver proteins. The purpose of this study was to evaluate the effect of
      nutritional and hormonal supplementation on these observations 24 h after LT. Two
      groups of nine pigs were studied 1 day after LT using radioisotopic and
      arteriovenous difference techniques. A control group underwent LT with saline
      infusion and a supplemented group underwent LT with infusion of glucose, amino
      acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg.
      min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were
      used to determine leucine flux, an estimate of whole body protein breakdown, and
      fractional synthetic rates (FSR). The following changes were noted with
      supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml,
      control versus supplemented, respectively, P < 0.05), decreased glucagon to
      normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased
      fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed
      liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin
      FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively).
      Nutritional and hormonal supplementation immediately after LT restored the
      measured protein synthesis in the allograft to near normal levels 1 day after
      transplantation.

PMID- 9927542
TI  - Salbutamol and the conditioning of latissimus dorsi for cardiomyoplasty.
AB  - BACKGROUND: Cardiomyoplasty is a new surgical alternative therapy for CHF.
      Although conditioning of muscle for cardiomyoplasty has a positive effect on
      fatigue resistance it also produces negative effects. In this study we assessed
      the effect of salbutamol, a beta2-agonist, on both the positive and the negative
      effects of conditioning. METHODS: In a control group of six animals one
      latissimus dorsi was subject to chronic, 1 Hz, low-frequency stimulation (CLFS)
      while the other served as a control. The experimental group of seven dogs
      received a continuous SC infusion of salbutamol and one latissimus dorsi was
      subjected to CLFS. The other muscle demonstrated the effects of salbutamol per
      se. After 42 days the animals were anesthetized and fatigue resistance, muscle
      mass, and mechanical properties of the muscles were evaluated. RESULTS:
      Salbutamol increased muscle mass, tetanic tension, and rate of rise and fall of
      tetanic tension. It diminished fatigue resistance and had no effect on shortening
      velocity. Chronic stimulation decreased muscle mass, tetanic tension, rate of
      rise and fall of tetanic tension, and muscle shortening velocity in both groups
      of dogs. Salbutamol diminished the declines in muscle mass, rate of tension
      development, and rate of muscle shortening due to CLFS, but did not change the
      effects of CLFS on tetanic tension and the rate of fall of tetanic tension.
      Salbutamol did not alter the increase in fatigue resistance induced by CLFS.
      CONCLUSIONS: The favorable effect of CLFS on fatigue resistance was unaffected by
      salbutamol. The unfavorable effects of CLFS on loss of muscle mass, rate of
      tension development, and decline in shortening velocity were partially blocked by
      salbutamol, improving the ability of the latissimus dorsi to augment cardiac
      systole.

PMID- 9927543
TI  - A novel conception for liver preservation at a temperature just above freezing
      point.
AB  - BACKGROUND: It is generally accepted that 0 to 4 degreesC is a suitable
      temperature for organ preservation. The reason for this is based on the premise
      that at temperatures below 0 degreesC, intracellular ice is likely to form, with
      subsequent damage to cellular structures. However, it cannot be assumed that
      subzero temperatures will freeze the cell. In this study, we attempted to confirm
      the specific freezing point of rat liver and to preserve it at a temperature just
      above that point. METHODS: Rat livers were stored for 24, 48, 72, and 96 h either
      at 4 degreesC (Group N) or at -0.8 degreesC (just above the temperature
      ascertained to be the specific freezing point of rat liver; Group H). After cold
      storage, the livers were perfused for 60 min using an isolated perfused liver
      model for assessment of liver function. RESULTS: ATP and TAN (total adenine
      nucleotides) in reperfused liver tissues were significantly higher in Group H
      than in Group N for all preservation periods. ADP was significantly higher in
      Group H than in Group N for 24-, 72-, and 96-h preservation periods. Energy
      charge was significantly higher in Group H than in Group N for 24-, 48-, and 96-h
      preservation periods. CONCLUSIONS: Regarding the content of ATP, ADP, and TAN and
      the adenylate energy charge, our results indicate that preservation at -0.8
      degreesC is advantageous. This novel preservation technique seems to prolong the
      period that organs can be stored.

PMID- 9927544
TI  - Cytokine suppressive agent improves survival rate in rats with acute pancreatitis
      of closed duodenal loop.
AB  - This study was designed to evaluate the possible role of cytokines (IL-1 and TNF
      alpha) in the pathogenesis of acute pancreatitis in the early stage of the
      disease and to evaluate the protective effect of the cytokine suppressive agent,
      FR167653, against pancreatic injuries. Acute pancreatitis was induced in rats by
      closed duodenal loop. However, the free passage for the gastrointestinal contents
      was maintained by inserting the tube into the duodenum. In this model, the
      survival rate was significantly decreased as compared with the control sham
      operated rats at 48 h after induction of pancreatitis. Marked hyperamylasemia and
      a significant increase in pancreatic water and trypsin contents were observed at
      24 h after induction of pancreatitis. Pancreatic subcellular redistribution of
      lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction
      was also observed. However, treatment with FR167653 at a dose of 1.5 mg/kg (four
      times, every 6 h after induction of pancreatitis) significantly prevented all
      these pancreatic injuries, improving the survival rate. These results indicate
      that cytokines such as IL-1 and TNF-alpha may be involved in the pathogenesis of
      acute pancreatitis in the early stage of the disease, and that a cytokine
      suppressive agent might be of therapeutic value for the treatment of acute
      pancreatitis.

PMID- 9927546
TI  - Keratinocyte growth factor-2 accelerates wound healing in incisional wounds.
AB  - BACKGROUND: Keratinocyte growth factor-2 (KGF-2) also described as fibroblast
      growth factor-10 (FGF-10) is a newly identified member of the fibroblast growth
      factor family. KGF-2 is 96% identical to the recently identified rat FGF-10 and
      specifically stimulates growth of normal human epidermal keratinocytes. The
      present study was undertaken to examine the effects of topically applied KGF-2 in
      an incisional wound healing model. KGF-2 treatment resulted in an improvement in
      incisional wound healing as characterized by an increase in breaking strength,
      collagen content, and epidermal thickness. METHODS: KGF-2 was topically applied
      to linear incisions made in the dorsal skin of Sprague-Dawley rats. Biomechanical
      testing was done using an Instron tensiometer for breaking and tensile strength
      determinations. Wound collagen content was determined using the Sircol collagen
      assay. Epidermal thickness measurements were conducted using Masson's trichrome
      stained sections of the wound. RESULTS: A single topical application of KGF-2 at
      the time of wounding resulted in an increase in wound breaking and tensile
      strength at Day 5 after wounding. Breaking strength of KGF-2-treated wounds was
      significantly higher compared with the buffer control (1 microgram, 222.1 +/-
      13.5 g, P = 0.0007; 4 microgram, 248.7 +/- 15.4 g, P = 0.0001; 10 microgram,
      247.2 +/- 21.9 g, P = 0.001; buffer, 141.0 +/- 9.7 g). Epidermal thickness and
      wound collagen content were significantly increased following treatment with KGF
      2. CONCLUSIONS: Based on our findings, KGF-2 is a potent stimulator of wound
      healing as demonstrated by increased mechanical strength accompanied by an
      increase in wound collagen content. KGF-2 could be an important cellular mediator
      responsible for the initiation and acceleration of wound healing and may enhance
      the healing of surgical wounds.

PMID- 9927545
TI  - The effect of neutrophil elastase inhibitor in hepatectomy with ischemia in dogs.
AB  - Activated neutrophils play an important role in reperfusion injury following
      hepatic ischemia. Neutrophil elastase is a powerful proteolytic enzyme. We
      investigated the possibility that ONO-5046. Na, which is a new recombinant
      specific neutrophil elastase inhibitor, can reduce ischemia and reperfusion
      injury in the canine liver. Adult mongrel dogs (n = 19) were used in this
      experimental study. Seventy-five percent of the liver was resected after 60 min
      of vascular occlusion. The animals were divided into two groups. The ONO group (n
      = 8) was given ONO-5046. Na dissolved in saline starting 30 min prior to clamping
      the hepatic inflow and continuing for 4 h after reperfusion at a rate of 10
      mg/kg/h. The nontreatment group (n = 11) received a saline solution for the same
      period. ALT and LDH levels were significantly lower (P < 0.05) in the ONO group
      than in the nontreatment group after reperfusion. Purine nucleoside phosphorylase
      and hyaluronic acid levels, which are markers of endothelial damage, were
      significantly lower (P < 0.05) in the ONO group than in the nontreatment group
      after reperfusion. Histologically, widely spread hepatocyte necrosis was found in
      dogs in the nontreatment group that died prematurely. Neutrophil infiltration of
      the sinusoids was less evident in the ONO group than in the nontreatment group.
      Neutrophil elastase inhibitor may prevent injuries of both endothelial and
      parenchymal cells in extended hepatectomy with vascular occlusion.

PMID- 9927547
TI  - A predominant increase of arterial beta-hydroxybutyrate concentration during
      partial hepatectomies in patients with impaired indocyanine green clearance test.
AB  - BACKGROUND: It has been reported that a concentration ratio of two ketone bodies,
      [acetoacetate]/[beta-hydroxybutyrate], reflects the redox state in the liver
      mitochondria, but there are few reports which examined each ketone body
      concentration during hepatectomy. Materials and Methods. (1) Ketone body levels
      in the radial artery and the hepatic vein were measured simultaneously during
      hepatectomies in 12 patients. (2) Arterial ketone body levels were measured
      during hepatectomies (at three points) in 73 patients. RESULTS: (1) Both ketone
      body levels in the radial artery well reflected those in the hepatic vein (P <
      0.001). (2) There was no change in the arterial acetoacetate level. The level of
      beta-hydroxybutyrate increased significantly from 30.4 to 76.5 micromol/L (P <
      0.005) only in the group of 25 patients with seriously impaired indocyanine green
      clearance test. CONCLUSIONS: Ketosis during hepatectomy was caused by increased
      beta-hydroxybutyrate, and this phenomenon was observed only in patients with
      seriously impaired liver function.

PMID- 9927548
TI  - Protein kinase C in normal and pathologic myocardial states.
AB  - Recent evidence has implicated protein kinase C (PKC) as an important mediator
      underlying multiple aspects of myocardial function. We and others have recently
      reported that PKC is involved in Ca2+-induced inotropy, in mediating myocardial
      preconditioning by diverse stimuli both in animals and humans, and in the
      signaling processes which lead to the production of proinflammatory mediators
      (cytokines). The purposes of this manuscript are to explore the role of PKC in
      normal myocardial contraction, the role of PKC in mediating protection, the role
      of PKC in inflammation, and the importance of inflammation regarding myocardial
      injury.

PMID- 9927549
TI  - Activation of lateral extrastriate areas during orthographic processing of
      Japanese characters studied with fMRI.
AB  - We investigated the early orthographic processing in the occipital cortex using
      Japanese morphogram by functional magnetic resonance imaging. Kanji (Japanese
      morphogram) is one system of character used in the Japanese language, each
      character of which has a specific meaning and pronunciations. To ensure that the
      effects of the general visual properties of Kanji were excluded from Kanji
      related activation, we created strict control stimuli, the "scrambled Kanji" that
      had the same luminance, contrast, and retinotopical size as those of the original
      Kanji. In the Kanji vs scrambled Kanji task, we found significant activation in
      the left inferior occipital gyrus. However, we found no activation in earlier
      visual cortices, including the primary visual cortex, indicating that the
      scrambled Kanji served as an effective control stimulus for this task. In the
      Kanji vs blank screen task, much more areas, including earlier visual cortices,
      were activated. The activation that we found in the Kanji vs scrambled Kanji task
      was compatible with the results of previous studies of English letter strings by
      other groups, suggesting that the left inferior occipital gyrus plays an
      essential role in orthographic processing common to these two different writing
      systems.

PMID- 9927550
TI  - Load-dependent roles of frontal brain regions in the maintenance of working
      memory.
AB  - Brain imaging studies have suggested a critical role for prefrontal cortex in
      working memory (WM) tasks that require both maintainenance and manipulation of
      information over time in delayed-response WM tasks. In the present study,
      functional magnetic resonance imaging (fMRI) was used to examine whether
      prefrontal areas are activated when only maintenance is required in a delayed
      response WM task, without the overt requirement to manipulate the stored
      information. In two scans, six subjects performed WM tasks in which, on each
      trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these
      letters across a 5-second unfilled delay, and (3) determined whether a single
      probe letter was or was not part of the memory set. Activation of left caudal
      inferior frontal gyrus was observed, relative to the 1-letter task, when subjects
      were required to maintain 3 letters in WM. When subjects were required to
      maintain 6 letters in WM, additional prefrontal areas, most notably middle and
      superior frontal gyri, were activated bilaterally. Thus, increasing the amount of
      to-be-maintained information, without any overt manipulation requirement,
      resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal
      gyrus activation was left-hemisphere dominant in both the 3- and 6-letter
      conditions, suggesting that such activation reflected material-specific verbal
      processes. Activation in middle and superior frontal gyri appeared only in the 6
      letter condition and was right-hemisphere dominant, suggesting that such
      activation reflected material-independent executive processes.

PMID- 9927551
TI  - Second order components of moving plaids activate extrastriate cortex: a positron
      emission tomography study.
AB  - A moving plaid is a composite pattern produced by superimposing two sinusoidal
      gratings which differ in orientation and motion direction. The perceived drift
      direction of a plaid appears to be determined partly by a binocular mechanism,
      which follows intersection of constraint rules (Burke and Wenderoth, 1993b), and
      partly by a monocular mechanism, which tracks the dark and bright intersects of
      the plaid, the contrast envelopes. The first neurones that respond to plaids as
      patterns rather than component gratings are found in area V5, also known as MT,
      which is exclusively binocular. Therefore, the psychophysical evidence suggesting
      that the contrast envelope tracking mechanism is monocular is surprising but has
      been obtained consistently. We aimed to localize the contrast envelope tracking
      mechanism by undertaking a positron emission tomography (PET) activation
      experiment in which the subjects were presented with alternating plaid components
      during the control scan and with the moving plaid resulting from the
      superposition of these components as the activation scan. The results showed
      differential activation in area V3. Recent results from macaque single cell
      recordings have also demonstrated increased sensitivity to moving plaid stimuli
      compared to the plaid component gratings in V3 neurones.

PMID- 9927552
TI  - Mapping of central D2 dopamine receptors in man using [11C]raclopride: PET with
      anatomic standardization technique.
AB  - D2 dopamine receptors are of interest in the pathophysiology of schizophrenia.
      For group comparisons of neuroreceptor distribution measured by PET on a pixel-by
      pixel basis, an anatomic standardization technique is required. The aim of the
      present study is to build a database of normal D2 dopamine receptor distribution
      using [11C]raclopride and an anatomic standardization technique. In each subject,
      two PET measurements were performed with rapid bolus injection and with
      continuous infusion of [11C]raclopride. The radioactivity of the PET images were
      integrated in the time interval. Integrated images were normalized by the
      radioactivity of the cerebellum, providing a measure of the binding potential
      (BP) in each pixel. Each PET image was transformed into a standard brain anatomy
      using a Computerized Brain Atlas system. From the standardized PET images, the
      sample mean and the SD of the BP were calculated in each pixel. On the
      anatomically standardized average images for the both rapid bolus injection and
      continuous infusion, high BP was observed in the putamen and the caudate nucleus,
      whereas low BP was observed in the cerebral cortices. The BP for the thalamus and
      the substantia nigra were slightly higher than those for the cerebral cortices.
      This regional distribution is in good agreement with the distribution of D2
      dopamine receptors known from in vitro studies. The anatomic standardization
      technique permits to build a database of the normal D2 dopamine receptor
      distribution in the living human brain. This technique can be applied for group
      comparisons on a pixel-by-pixel basis.

PMID- 9927553
TI  - Functional MRI of human brain during breath holding by BOLD and FAIR techniques.
AB  - BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating
      inversion recovery) imaging techniques were used to investigate the oxygenation
      and hemodynamic responses of human brain during repeated challenges of breath
      holding and prolonged single breath holding. The effects of different breathing
      techniques on BOLD and FAIR image contrasts were carefully examined. With a
      periodic breath-holding paradigm of 30 s, global changes in gray matter were
      observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1-4%
      relative signal intensity increases, while FAIR images demonstrated relative
      cerebral blood flow (CBF) increase up to 30-70%. The activated pixels depicted in
      FAIR images were about three times less than those seen in T*2-weighted images.
      With prolonged breath holding, it was observed that signal intensities in T*2
      weighted and FAIR images were dependent on the breathing techniques used. Breath
      holding after expiration gave rise to immediate signal intensity increases in T*2
      weighted and FAIR images, whereas breath holding performed after deep inspiration
      signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and
      FAIR signals showed a transient decrease before rising above the baseline level.

PMID- 9927554
TI  - A method for assessing the accuracy of intersubject registration of the human
      brain using anatomic landmarks.
AB  - Several groups have developed methods for registering an individual's 3D MRI by
      deforming a standard template. This achievement leads to many possibilities for
      segmentation and morphology that will impact nuclear medical research in areas
      such as activation and receptor studies. Accordingly, there is a need for methods
      that can assess the accuracy of intersubject registration. We have developed a
      method based on a set of 128 anatomic landmarks per hemisphere, both cortical and
      subcortical, that allows assessment of both global and local transformation
      accuracy. We applied our method to compare the accuracy of two standard methods
      of intersubject registration, AIR 3.0 with fifth-order polynomial warping and the
      Talairach stereotaxic transformation (Talairach and Tournoux, 1988). SPGR MRI's
      (256 x 256 x 160) of six normal subjects (age 18-24 years) were derformed to
      match a standard template volume. To assess registration accuracy the landmarks
      were located on both the template volume and the transformed volumes by an
      experienced neuroanatomist. The resulting list of coordinates was analyzed
      graphically and by ANOVA to compare the accuracy of the two methods and the
      results of the manual analysis. ANOVA performed over all 128 landmarks showed
      that the Woods method was more accurate than Talairach (left hemisphere F = 2.8,
      P < 0.001 and right hemisphere F =2.4, P < 0.006). The Woods method provided a
      better brain surface transformation than did Talairach (F = 18.0, P < 0.0001),
      but as expected there was a smaller difference for subcortical structures and
      both had an accuracy <1 mm for the majority of subcortical landmarks. Overall,
      both the Woods and Talairach method located about 70% of landmarks with an error
      of 3 mm or less. More striking differences were noted for landmark accuracy </=1
      mm, where the Woods method located about 40% and Talairach about 23%. These
      results demonstrate that this anatomically based assessment method can help
      evaluate new methods of intersubject registration and should be a helpful tool in
      appreciating regional differences in accuracy. Consistent with expectation, we
      confirmed that the Woods nonlinear registration method was more accurate than
      Talairach. Landmark-based anatomic analyses of intersubject registration accuracy
      offer opportunities to explore the relationship among structure, function and
      architectonic boundaries in the human brain.

PMID- 9927555
TI  - Naturally occurring antimicrobials in food.

PMID- 9927556
TI  - A survey of lead-based paint abatement projects performed in public buildings in
      Erie and Crawford Counties, Pennsylvania, during the time period 1995-1997.
AB  - A survey of lead-based paint abatement projects in public buildings of Crawford
      and Erie Counties, Pennsylvania, was conducted during the time period January
      1995 to March 1997. These survey results suggest that few lead abatement projects
      were performed during this time period. Projects that were performed commonly did
      not employ proper lead abatement practices as described by the U.S. Occupational
      Safety and Health Administration, U.S. Environmental Protection Agency, and U.S.
      Department of Housing and Urban Development. These data suggest that most
      contractors and public officials have misunderstandings of both environmental
      regulations and required procedures for safe and effective lead-based paint
      abatement.

PMID- 9927557
TI  - Hygienic classification of pesticides in the Russian Federation.
AB  - Hygienic classifications of pesticides used in the Russian Federation are
      presented. The classifications cover both technical products and preparative
      forms of pesticides. Four classes of hazards are distinguished: extremely
      hazardous, hazardous, moderately hazardous, and slightly hazardous. These four
      classes are used for classifying general toxicity (peroral, skin, inhalation),
      cumulative, allergic, teratogenic, embryotoxic, reproductive, mutagenic,
      carcinogenic effects, and the stability in soil. The class of the hazard is
      determined on the basis of toxicohygienic evaluation of a pesticide, taking into
      account a limiting criterion of the hazard.

PMID- 9927558
TI  - Identification of rodent carcinogens and noncarcinogens using genetic toxicity
      tests: premises, promises, and performance.
AB  - The basic premises that guide genetic toxicity testing for identifying
      carcinogens and to support administrative and regulatory decisions are: the
      Salmonella mutagenicity test is a necessary component of testing schemes; a
      chromosome aberration test is needed in addition to a gene mutation test; a
      mammalian cell mutagenicity test is needed in addition to the Salmonella test; in
      vivo tests are needed to confirm the results of in vitro tests; and test
      batteries are more predictive than the individual tests of the battery. Results
      from the Salmonella mutagenicity, in vitro chromosome aberration, mutations in
      mouse lymphoma cells, rodent bone marrow micronucleus, and rodent carcinogenicity
      tests, performed by the U.S. National Toxicology Program, were used to evaluate
      these premises. A positive Salmonella test was most predictive of
      carcinogenicity. However, the data do not support using the other tests in
      addition to Salmonella for predicting carcinogenicity. The genetic toxicity tests
      did not complement each other, and batteries or combinations of the tests were no
      more predictive of carcinogenicity than Salmonella alone. If a chemical is
      mutagenic in Salmonella it should be considered a potential rodent carcinogen,
      unless ancillary information suggests otherwise. Positive responses in the other
      in vitro or in vivo tests do not increase the probability that the chemical is a
      carcinogen, and negative responses in the other tests do not diminish the
      implications of the positive Salmonella response.

PMID- 9927559
TI  - Uncertainty analysis methods for comparing predictive models and biomarkers: A
      case study of dietary methyl mercury exposure.
AB  - Biologically based markers (biomarkers) are currently used to provide information
      on exposure, health effects, and individual susceptibility to chemical and
      radiological wastes. However, the development and validation of biomarkers are
      expensive and time consuming. To determine whether biomarker development and use
      offer potential improvements to risk models based on predictive relationships or
      assumed values, we explore the use of uncertainty analysis applied to exposure
      models for dietary methyl mercury intake. We compare exposure estimates based on
      self-reported fish intake and measured fish mercury concentrations with biomarker
      based exposure estimates (i.e., hair or blood mercury concentrations) using a
      published data set covering 1 month of exposure. Such a comparison of exposure
      model predictions allowed estimation of bias and random error associated with
      each exposure model. From these analyses, both bias and random error were found
      to be important components of uncertainty regarding biomarker-based exposure
      estimates, while the diary-based exposure estimate was susceptible to bias.
      Application of the proposed methods to a simple case study demonstrates their
      utility in estimating the contribution of population variability and measurement
      error in specific applications of biomarkers to environmental exposure and risk
      assessment. Such analyses can guide risk analysts and managers in the appropriate
      validation, use, and interpretation of exposure biomarker information.

PMID- 9927560
TI  - Linear extrapolation models of lung cancer risk associated with exposure to
      environmental tobacco smoke.
AB  - This paper presents a model to estimate the number of lung cancer deaths due to
      ETS exposure among the 1992 U.S. never-smoking population, based on downward
      linear extrapolation from the estimated risks of active smokers. The model uses
      several recently available data sources including an extensive review of the
      published literature on indoor concentration of ETS constituents measured under
      real-world conditions and data from the National Mortality Followback Survey and
      the National Health Interview Survey which furnish nationally representative
      estimates of the distribution of the U.S. population and the persons who died
      from lung cancer by sex, age, and smoking status. The linear extrapolation model
      estimates that five male and six female excess lung cancer deaths due to ETS
      exposure would be expected in the 1992 U.S. population of over 52 million never
      smokers age 35 and over. Explanations for differences between the results of our
      downward extrapolation model and those of others are presented.

PMID- 9927561
TI  - Veterinary drugs no longer need testing for carcinogenicity in rodent bioassays.
AB  - The putative carcinogenic risk to humans from ingestion of edible tissues
      containing traces of nongenotoxic veterinary drugs is so slight that the routine
      application of rodent cancer bioassays cannot be justified. This argument is
      based, first, on the pharmacological similarity of veterinary and human drugs:
      many of the latter that are carcinogenic to rodents have been deemed on
      mechanistic and/or potency grounds not to pose a cancer risk to humans. Second,
      the distribution of a veterinary drug through the target animal body before
      ingestion of a portion of edible tissue by humans days or weeks later means that
      the human dose from a residue is several orders of magnitude lower than the
      normal dose of human drugs. The dose of residue is also much lower than the
      exposure of humans to the most potent carcinogens.

PMID- 9927562
TI  - Binding of drugs to eye melanin is not predictive of ocular toxicity.
AB  - Ocular melanin is found in the uveal tract and in the pigmented epithelial layer
      of the retina. Many structurally and pharmacologically unrelated drugs from
      different therapeutic classes bind to melanin. Examples include numerous drugs
      acting on the central nervous system, beta-blockers, beta-agonists, antimalarial
      drugs, sympathomimetic amines, and antibiotics. The critical factors are the
      acid/base status and the lipophilicity of the molecule. In all cases, there are
      no direct consequences of drug-melanin binding. Drug-related toxic effects on the
      retina described in humans and animals are unrelated to melanin binding: melanin
      binding and retinal toxicity are two separate entities, the latter being related
      to the intrinsic toxicity of the compound rather than its ability to bind.
      Chloroquine and phenothiazines are often used as examples of drugs with retinal
      toxicity linked to melanin binding. In both cases however, experimental data show
      that the toxic mechanism is unrelated to binding. Melanin binding has also been
      found to be protective against the ocular toxicity of some drugs. In conclusion,
      we believe that potential ocular toxicity of future drugs can be assessed
      adequately by conducting well-designed toxicology studies, and using nonpigmented
      rodents in addition to pigmented nonrodent species remains fully justified.
      Binding of drugs to eye melanin is not predictive of ocular toxicity.

PMID- 9927563
TI  - Dose-response characteristics of uterine responses in rats exposed to estrogen
      agonists.
AB  - Assays for uterine response have played major roles in developing an
      understanding of estrogen-mediated processes and for identifying compounds with
      hormonal activity. Data from assays measuring increases in uterine wet weight in
      rats were evaluated in terms of their dose-response characteristics. Analysis
      using a Hill equation found inconsistent estimates for the ED50 (concentration
      giving half-maximal response) and n (steepness of response) among the assays.
      This variability reflects disparate assay protocols and limitations of the dose
      response data collected in the experiments. Although uterine wet weight is easily
      measured, it arises from several physiological processes (e.g., water retention,
      cell proliferation). This contributes to the assay variability with different
      protocols. The potential use of the Hill equation for dose-response analysis to
      estimate a benchmark dose was also considered using these data sets as surrogates
      for receptor-mediated toxicological effects. Strengths and weaknesses were
      identified, but overall the Hill equation should likely become a favored option
      for determining a benchmark dose, particularly when a data set demonstrates a
      maximal response. For screening purposes, empirical analysis using the Hill
      equation provides adequate information for classifying and prioritizing
      compounds. To develop an understanding of how incremental exposures to compounds
      with estrogen agonist activities would affect intact adult females, quantitative
      analyses are required that account for the pharmacokinetics of estradiol and
      subsequent interactions of the receptor complexes in regulating the responses.

PMID- 9927564
TI  - Procedures for calculating benchmark doses for health risk assessment.
AB  - Safety assessment for noncancer health effects generally has been based upon
      dividing a no observed adverse effect (NOAEL) by uncertainty (safety) factors to
      provide an acceptable daily intake (ADI) or reference dose (RfD). Since the NOAEL
      does not utilize all of the available dose-response data, allows higher ADI from
      poorer experiments, and may have an unknown, unacceptable level of risk, the
      benchmark dose (BD) with a specified, controlled low level of risk has become
      popular as an adjunct to the NOAEL or the low observed adverse effect level
      (LOAEL) in the safety assessment process. The purpose of this paper is to
      summarize statistical procedures available for calculating BDs and their
      confidence limits for noncancer endpoints. Procedures are presented and
      illustrated for quantal (binary), quasicontinuous (proportion), and continuous
      data. Quasicontinuous data arise in developmental studies where the measure of an
      effect for a fetus is quantal (normal or abnormal) but the experimental unit is
      the mother (litter) so that results can be expressed as the proportion of
      abnormal fetuses per litter. However, the correlation of effects among fetuses
      within a litter poses some additional statistical problems. Also, developmental
      studies usually include some continuous measures, such as fetal body weight or
      length. With continuous data there generally is not a clear demarcation between
      normal and adverse measurements. In such cases, extremely high and/or low
      measurements at some designated percentile(s) can be considered abnormal. Then
      the probability (risk) of abnormal individuals can be estimated as a function of
      dose. The procedure for estimating a BD with continuous data is illustrated using
      neurotoxicity data. When multiple measures of adverse effects are available, a BD
      can be estimated based on a selected endpoint or the appearance of any
      combination of endpoints. Multivariate procedures are illustrated using
      developmental and reproductive toxicity data.

PMID- 9927565
TI  - Aggregate exposures under the Food Quality Protection Act: An approach using
      chlorpyrifos.
AB  - The Food Quality Protection Act of 1996 (Public Law 104-170, August 3, 1996),
      which amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and
      the Federal Food, Drug, and Cosmetic Act (FFDCA), requires that the EPA evaluate
      pesticide safety in light of potential aggregate exposures from both nondietary
      and dietary routes. As with any new legislation, there has been considerable
      discussion and challenges presented within the regulatory and scientific
      communities regarding the effective implementation of this act as it relates to
      the determination of aggregate exposures. This paper describes a novel
      methodology incorporating personal exposure factors, route-specific exposure
      measurements, and usage information to characterize potential aggregate exposures
      to a widely used pesticide, chlorpyrifos. A calendar model framework has been
      developed to describe potential multipathway exposures to individuals. The model
      assimilates information regarding the typical use patterns of chlorpyrifos
      containing pesticides in concert with quantitative exposure and dose measurements
      to estimate the probability and magnitude of exposures to members of the U.S.
      population. Studies measuring 3,5,6-trichloropyridinol, the primary metabolite of
      chlorpyrifos, in the urine of individuals within the United States show that
      aggregate exposures derived from this approach are consistent with actual
      population-based exposures to chlorpyrifos. According to this assessment,
      potential health risks attributed to exposure to chlorpyrifos are low when
      compared to relevant toxicological end points.

PMID- 9927566
TI  - Recent bioassay results on coal tars and benzo(a)pyrene: implications for risk
      assessment.

PMID- 9927567
TI  - EDITOR'S COMMENT 

PMID- 9927568
TI  - The bovine Newbury agent-2 is genetically more closely related to human SRSVs
      than to animal caliciviruses.
AB  - The hypothesis that the enteric bovine calici-like virus Newbury agent (NA-2)
      belongs to the family Caliciviridae was examined by genome sequence analysis. Use
      of solid-phase immune electron microscopy allowed samples with good levels of
      virus to be identified and amplification of the genome was achieved by reverse
      transcription-polymerase chain reaction. Examination of a 216-amino-acid sequence
      in the RNA-dependent RNA polymerase gene and a 116-amino-acid sequence in the
      capsid gene showed that NA-2 had the closest deduced amino acid identity (77 to
      80% for the polymerase region and 67 to 73% for the capsid region) to the
      morphologically indistinguishable human SRSVs (small round structured viruses) of
      genogroup 1, which are classified as members of the Caliciviridae. It had a weak
      relationship (<34.5% deduced amino acid identity) in both the polymerase and the
      capsid regions to animal caliciviruses, all of which have classical morphology.
      This is the first genomic data from a nonhuman virus with SRSV morphology. It
      confirms the hypothesis that the bovine enteric calici-like virus NA-2 is a
      member of the family Caliciviridae and endorses the observation to date that
      viruses with SRSV morphology are genomically distinct.

PMID- 9927569
TI  - Interaction of the capsid protein p24 (HIV-1) with sequence-derived peptides:
      influence on p24 dimerization.
AB  - Protein-protein interactions of the p24 (HIV-1) capsid protein play an essential
      role in the production of infectious virus particles. To map the putative p24
      dimerization site, a set of overlapping peptides spanning the p24 sequence was
      prepared using spot synthesis on a cellulose membrane and probed with recombinant
      p24 (rp24). Three sequence regions interacting with rp24 were identified.
      Peptides from each region were synthesized, but only one peptide was effectively
      able to inhibit rp24 dimerization in solution. Amino acids that were exposed in
      the corresponding p24 region were mutated in rp24, resulting in a significant
      decrease of rp24 dimerization. Thus, participation of this region in virus capsid
      assembly can be assumed.

PMID- 9927570
TI  - Coexpression of the adenovirus 12 E1B 55 kDa oncoprotein and cellular tumor
      suppressor p53 is sufficient to induce metaphase fragility of the human RNU2
      locus.
AB  - Adenovirus 12 (Ad12), but not adenovirus 2 or 5, induces metaphase chromosome
      fragility at four specific loci in humans: RNU1, RNU2, PSU1, and RN5S. As each of
      these sites corresponds to a tandemly repeated multigene family encoding a small,
      abundant structural RNA, we proposed that Ad12 hinders metaphase chromatin
      condensation, interfering either directly or indirectly with transcriptional
      regulation or chromatin packing of these small RNA genes. We and others
      subsequently found that Ad12-induced fragility of the RNU2 locus requires U2
      promoter elements, viral early functions, and p53. We now show that RNU2
      fragility can be induced by transfection with an expression vector encoding Ad12
      E1B 55 kDa alone but not by an E1 vector encoding all E1 products (3 E1A
      proteins, as well as the E1B 19 kDa and 55 kDa proteins). Although Ad12 E1B 55
      kDa efficiently induced fragility in transfected cells, Ad2 E1B 55 kDa did not.
      By swapping domains between the Ad12 and Ad2 E1B, we found that the aminoterminus
      of Ad12 E1B is required for induction of fragility and that the ability of the
      hybrid E1B proteins to induce fragility appears to correlate with nuclear
      localization. Furthermore, in Saos-2 cells lacking p53 function, RNU2 fragility
      could be induced by cotransfection with vectors encoding Ad12 E1B 55 kDa and
      either wild-type p53 or the R273H mutant with impaired DNA binding activity. We
      conclude that a functional (and probably physical) interaction between Ad12 E1B
      55 kDa and p53 within the nucleus is sufficient to induce metaphase fragility of
      the RNU2 locus.

PMID- 9927571
TI  - Cellular expression of bovine herpesvirus 1 gD inhibits cell-to-cell spread of
      two closely related viruses without blocking their primary infection.
AB  - Alphaherpesviral glycoprotein D (gD) is a critical component of the cell membrane
      penetration system. Cells that express gD of herpes simplex virus type 1 (HSV1),
      pseudorabies virus (PRV), or bovine herpesvirus type 1.1 (BHV1.1) resist
      infection by the homologous virus due to interference with viral entry at the
      level of penetration. BHV1.1 gD interferes with the distantly related viruses
      HSV1 and PRV despite only a 30-40% sequence similarity and the complete absence
      of antigenic cross-reactivity among the three gDs. The six cysteines that form
      three intrachain disulfide bonds in HSV1 are also present in PRV and BHV1.1 gD,
      suggesting structural similarities among the gD homologs. Functional similarities
      were postulated to be responsible for cross-interference. To test this
      hypothesis, we constructed a BHV1.1 gD-expressing cell line (MDBKgD) and assessed
      its resistance to the homologous BHV1.1 and two closely related viruses, BHV1.2
      and BHV5. The gDs of these viruses share 98. 3% and 86% amino acid identity with
      BHV1.1 gD and bound monoclonal antibodies directed against all five neutralizing
      epitopes mapped on BHV1.1 gD. MDBKgD cells were resistant to BHV1.1 but fully
      susceptible to BHV1.2 and BHV5 infection as measured by plaque numbers and single
      cycle growth kinetics. However, all three viruses, but not vesicular stomatitis
      virus, made smaller plaques on MDBKgD cells than on control cells. These data
      suggest that gD-mediated interference is expressed both at the level of initial
      infection and at the level of cell-to-cell spread and that these two levels can
      be distinguished by using closely related viruses.

PMID- 9927572
TI  - A particulate viral protein vaccine reduces viral load and delays progression to
      disease in immunized ponies challenged with equine infectious anemia virus.
AB  - Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL)
      response specific for lentiviral antigens have emerged as the leading candidates
      in efficacy trials conducted in both animal modelshumans. To date, lentivirus
      vaccination strategies have overlooked one such immunization strategy, namely the
      use of particulate antigens. To evaluate the efficacy of targeting antigen into
      the phagocytic pathway to elicit a cell-mediated immune response to lentiviral
      antigens, we initiated the first study of a particulate-based vaccination
      protocol using a large animal model system. Gradient-purified equine infectious
      anemia virus (EIAV) was covalently coupled to glutaraldehyde-activated iron oxide
      beads. In vitro studies demonstrated the effectiveness of the inactivated whole
      virus particulate to prime antigen presenting cells for the activationexpansion
      of virus-specific CD8(+) CTL. The in vivo effectiveness of the particulate
      antigen was evaluated by experimental immunization of ponies. Ponies receiving
      the viral particulate vaccinechallenged with infectious EIAV had a delayed
      progression to diseasea reduced viral load compared with infected ponies that had
      not been vaccinated. Interestingly, in vitro virus-specific CTL activity was
      detected in only one of four immunized animals at the day of challenge. The
      beneficial effects of the particulate vaccine regimen were not clearly associated
      with any in vitro measurable parameters of the virus-specific cellular or humoral
      immune responses elicited by the vaccine at the day of challenge. However, within
      3 weeks after virus challenge, anamnestic humoral responses characterized by a
      rapid emergence of neutralizing activity in the seruma predominance of
      conformationally dependent epitopes recognized by virus-specific antibodies were
      observed in the vaccinates. Taken together, further studies are clearly warranted
      in large animal model systems using a particulate-based vaccine regimen
      considering the beneficial effects of this regimen in our studythe protective
      effects of particulate antigen delivery in the murine model.

PMID- 9927573
TI  - Heterosubtypic immunity to lethal influenza A virus infection is associated with
      virus-specific CD8(+) cytotoxic T lymphocyte responses induced in mucosa
      associated tissues.
AB  - Heterosubtypic immunity, defined as cross-reactive immune responses to influenza
      virus of a different serotype than the virus initially encountered, was
      investigated in association with virus-specific cytotoxic T lymphocyte (CTL)
      responses induced in systemic and mucosa-associated lymph nodes after
      immunization via different routes. Mice immunized by the pulmonary route with
      live nonpathogenic influenza virus, strain Udorn (H3N2), survived challenge with
      mouse-adapted pathogenic influenza virus, strain PR/8/34 (H1N1). These mice
      developed strong heterosubtypic CTL responses in spleen, cervical lymph nodes
      (CLN), and mediastinal lymph nodes (MLN). Alternately, only 20% of mice immunized
      intravenously, intraperitoneally, or intranasally survived the challenge; all of
      these developed CTL responses in spleen and CLN, but not in MLN. Direct
      correlation between short-term and long-term memory heterosubtypic CTL responses
      induced in MLN and host recovery after lethal infection indicates that these CTL
      responses may play an important role in heterosubtypic immunity. Furthermore,
      induction and maintenance of memory CTL in regional mucosa-associated lymphoid
      tissues are highly dependent on mucosal immunization. The results implicate the
      mechanism of heterosubtypic immunity and should be an important consideration in
      the development of protective mucosal vaccines against variant strains of
      influenza and HIV.

PMID- 9927574
TI  - Selection of the R17Y substitution in SIVmac239 nef coincided with a dramatic
      increase in plasma viremia and rapid progression to death.
AB  - Three rhesus macaques were infected with an SIVmac239 variant containing
      substitutions of 73/74PA-->ED and 204D-->R in Nef that disrupted the ability of
      Nef to downregulate CD4 surface expression. One of these animals, Mm8155, rapidly
      progressed to AIDS and died 21 weeks postinfection. During the final 5 weeks of
      infection, the levels of viral RNA and of p27 antigenemia were about 100-fold
      higher than usually observed in SIVmac239 infection. Postmortem examination
      revealed giant cell disease of the lymph nodes and the gastrointestinal tract,
      opportunistic infections, and a severe chronic enteritis. The majority of
      proviruses in spleen, kidney, and lymph nodes, and almost 100% of the viral RNA
      sequences, contained mutations of CGA-->TAT in codon 17 of nef, predicting a
      change of 17R-->Y. The appearance of this substitution, which has recently been
      shown to confer the phenotype of the acutely pathogenic SIVpbj14, coincided with
      the dramatic increase in viral load and rapid progression to fatal disease. In
      comparison, reversions of 204R-->D and changes of 72-74NED-->DKD, which restored
      the ability of Nef to downregulate CD4, were already selected earlier in
      infection. Similarly to SIVpbj14, virus reisolated at late time points from
      Mm8155 replicated efficiently in unstimulated monkey lymphocytes. The Y17
      substitution was not detected in 14 additional SIVmac239-infected macaques at the
      time of AIDS-related death or in the two slowly progressing animals initially
      infected with the same Nef variant. Although infection of macaques with SIV is
      commonly used as an animal model for HIV-1 infection in humans, this is only the
      second example for the emergence of an acutely lethal SIVmac Nef variant.

PMID- 9927575
TI  - Neutralizing and protective antibodies directed against vaccinia virus envelope
      antigens.
AB  - The infection mechanism of vaccinia virus is largely unknown. Neither the
      attachment protein of extracellular enveloped virus (EEV), the biologically
      relevant infectious form of the virus, nor its cellular receptor has been
      identified. Surprisingly, all former attempts using antibodies to block EEV
      infection of cells in vitro had failed. Here, we report the production of an anti
      envelope hyperimmune serum with EEV neutralizing activity and show that a
      polyclonal antiserum against the extraviral domain of protein B5R also inhibited
      EEV infection. In vivo, mice vaccinated with B5R protein were protected against a
      lethal vaccinia virus challenge. This protectivity is likely to be mediated by
      neutralizing antibodies. Protein A33R, but not A34R and A36R, also proved to be
      protective in active and passive vaccination experiments. However, in contrast to
      B5R, A33R protectivity did not correlate with antibody titers. Because anti-A33R
      antibodies did not neutralize EEV in vitro, the protectivity mediated by A33R
      protein probably involves a mechanism different from simple antibody binding.
      Taken together, our results suggest that antibodies to a specific protective
      epitope or epitopes on protein B5R are able to prevent EEV infection. The protein
      encoded by the B5R gene is therefore likely to play a crucial role in the initial
      steps of vaccinia virus infection-binding to a host cell and entry into its
      cytoplasm.

PMID- 9927576
TI  - Recombinant vesicular stomatitis virus expressing respiratory syncytial virus
      (RSV) glycoproteins: RSV fusion protein can mediate infection and cell fusion.
AB  - The genes encoding the respiratory syncytial virus (RSV) attachment (G) and
      fusion (F) envelope glycoproteins were expressed separately as additional genes
      in recombinant vesicular stomatitis viruses (VSV). Cells infected with the VSV
      RSV F recombinant formed large syncytia illustrating the fusion activity of F in
      absence of other RSV proteins. Both F and G glycoproteins were expressed at the
      cell surface and incorporated into virions. Incorporation of these proteins did
      not require cytoplasmic tail sequences of VSV G. Using a compound, ammonium
      chloride, that raises the endosomal pH, we showed that presence of the RSV F
      glycoprotein in the envelope of recombinant VSV allowed for infectivity through a
      low-pH-independent pathway. Recombinant VSV expressing RSV glycoproteins could be
      useful as an RSV vaccine.

PMID- 9927577
TI  - Mapping sequences active in homologous RNA recombination in brome mosaic virus:
      prediction of recombination hot spots.
AB  - The mechanism of homologous recombination has been studied previously in brome
      mosaic virus (BMV), a tricomponent, positive-stranded RNA virus of plants, by
      using artificial sequences (reviewed by J. J. BujarskiP. D. Nagy (1996). Semin.
      Virol. 7, 363-372). Here we extend these studies over BMV-derived sequences to
      obtain clues on prediction of homologous recombination hot spots. First, mismatch
      mutations, which reduced the AU content, were introduced into the common 60-nt
      recombination hot-spot sequence, either in the RNA2 or in both RNA2RNA3
      components. This decreased the frequency of targeted homologous RNA2/RNA3
      recombinationchanged the distribution of junction sites. Second, several short
      BMV RNA1- or RNA2-derived sequences were introduced into the RNA3 component,
      homologous recombination activity of these sequences was compared with that
      observed for previously characterized artificial sequences. Third, sequences at
      homologous recombinant junctions were compared among a large number of
      targetednontargeted recombinants. All these studies revealed several factors
      important for homologous recombination including the length of sequence identity,
      the extent of sequence identity, the AU content of the common sequences, the
      relative position of the AU-rich segment vs a GC-rich segment,the presence of GC
      rich sequences. Based on this novel model, we suggest that recombination hot
      spots can be predicted by means of RNA sequence analysis. In addition, we show
      that recombination can occur between positivenegative strands of BMV RNAs. This
      provides further clues toward the mechanism of recombination processes in BMV.

PMID- 9927578
TI  - Satellite RNA is essential for encapsidation of groundnut rosette umbravirus RNA
      by groundnut rosette assistor luteovirus coat protein.
AB  - Groundnut rosette disease is caused by a complex of agents comprising groundnut
      rosette umbravirus (GRV), GRV satellite RNA (sat-RNA)groundnut rosette assistor
      luteovirus (GRAV). Both GRAV and GRV sat-RNA are needed for GRV to be aphid
      transmissible. To understand the role of GRAVGRV sat-RNA in the aphid
      transmission of GRV, encapsidation of GRV genomicsatellite RNAs has been studied
      using transgenic Nicotiana benthamiana plants expressing GRAV coat protein (CP).
      GRAV CP expressed from a transgene was shown to package GRV genomicsatellite RNAs
      efficiently, giving a high yield of transcapsidated virus particles. GRV sat-RNA
      was absolutely essential for this process. GRV genomic RNA was not encapsidated
      by GRAV CP in the absence of the sat-RNA. Using different mutants of GRV sat-RNA,
      it was found that some property of full-length satellite RNA molecules, such as
      size or specific conformation rather than potential open reading frames, was
      required for the production of virus particles. A correlation between the ability
      of sat-RNA to stimulate encapsidation of GRV RNA by GRAV CPits capacity to
      promote aphid transmission of GRV was observed.

PMID- 9927579
TI  - Characterization of the surface proteins of influenza A (H5N1) viruses isolated
      from humans in 1997-1998.
AB  - Influenza A (H5N1) viruses infected humans in Hong Kong between May and December,
      1997. Sixteen viruses, including 6 from fatal cases, were isolated during this
      outbreak. Molecular analysis of the surface proteins genes encoding the
      hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype
      not previously known to infect humans, are presented. The 16 human H5 HA
      sequences contain multiple basic amino acids adjacent to the cleavage site, a
      motif associated with highly pathogenic avian influenza A viruses. The
      phylogenetic relationship among both avian and human H5 hemagglutinins indicates
      that the human isolates are related directly to isolates that circulated among
      chickens in the live poultry markets in Hong Kong prior to and during the
      outbreak in humans. HA sequences from the human isolates and a recent chicken
      isolate represent a separate clade, within which there are two subgroups that are
      distinguishable antigenically and by the presence of a potential glycosylation
      site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade
      that is evolutionarily distinct from previously characterized N1 neuraminidases.
      The recent human H5N1 virus NA genes are avian-like, indicating direct
      introduction from an avian source rather than evolution of a human N1 NA. All of
      the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion,
      also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino
      acids were identified in the N1 NAs of the recent human isolates; however, it is
      not known if these residues influence host range. Neither the HA nor the NA genes
      of the human H5N1 virus isolates show evidence of adaptive changes during the
      outbreak. Although analyses of the surface protein genes of the H5N1 viruses from
      this outbreak did not provide immediate answers regarding the molecular basis for
      virulence, the analyses provided clues to potentially important areas of the
      genes worth further investigation.

PMID- 9927580
TI  - Analysis of the site occupancy constraints of primary amino acid sequences in the
      motif directing palmitylation of the vaccinia virus 37-kDa envelope protein.
AB  - Vaccinia virus (VV) encodes a 37-kDa envelope protein (p37) that is palmitylated
      on cysteine residues 185186 of the 372-amino acid protein. We have previously
      reported on a loosely conserved consensus motif. Further analysis has identified
      a conserved consensus sequence, Hydro*AAC(C)A (Hydro* represents a hydrophobic
      portion of a protein determined by any one of the following: a hydrophobic
      sequence, a transmembrane domain 1-12 amino acids away from the modification
      site, or the prior addition of a hydrophobic molecule; C, palmitate acceptor
      cysteines; A, aliphatic residue) that is responsible for directing palmitylation
      of certain classes of palmitylproteins. We have analyzed the amino acid site
      occupancy upstreamdownstream of the palmitate acceptor residues in p37 by site
      directed mutagenesistransient expression of mutated proteins in VV-infected
      cells. The two aliphatic alanines naturally found at positions 183184 of the wild
      type p37 allow for efficient palmitylation. In contrast, the replacement of
      leucine at position 187 with glycine increases palmitylation efficiency. The 10
      amino acids immediately upstream of the palmitate acceptor site are absolutely
      necessary while the downstream 10 amino acids are dispensable. These results
      together with previous data suggests that the Hydro*AAC(C)A motif is required for
      efficient palmitylation of p37.

PMID- 9927581
TI  - Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies
      specific for the transmembrane proteins matrix 2 and neuraminidase reduces the
      pulmonary virus titer but fails to clear the infection.
AB  - Antibodies (Abs) can contribute to the cure of a viral infection, in principle,
      in two ways by: (1) binding to infected cells and thereby reducing the production
      of progeny virus [here termed cell-targeting (CT) activity] and (2) reacting with
      released progeny virus and thereby inhibiting the spread of the infection [termed
      virus neutralizing (VN) activity]. We have previously shown that a pulmonary
      influenza virus infection in severe combined immunodeficient mice could be cured
      by treatment of these mice with hemagglutinin (HA)-specific monoclonal Abs (mAbs)
      that mediated both of the above activities. Although the therapeutic activity of
      these mAbs correlated with their VN activity, it remained unclear how much their
      CT activity contributed to the Ab-mediated recovery process. To clarify this
      point, we tested the therapeutic efficacy of two mAbs of IgG2a isotype that
      mediated CT but no VN activity: one specific for the viral neuraminidase and the
      other for matrix protein 2. Both mAbs reduced pulmonary virus titers by 100- to
      1000-fold but they failed to clear the infection, even when administered in
      combination and at therapeutically saturating concentrations. The results suggest
      that CT activity contributes significantly also to the therapeutic activity of HA
      specific mAbs and further support the notion that VN-activity is required for Ab
      mediated virus clearance.

PMID- 9927582
TI  - Paramyxovirus fusion protein: characterization of the core trimer, a rod-shaped
      complex with helices in anti-parallel orientation.
AB  - The fusion (F) protein of the paramyxovirus SV5 contains two heptad repeat
      regions, HRA adjacent to the fusion peptide and HRB proximal to the transmembrane
      domain. Peptides, N-1 and C-1, respectively, corresponding to these heptad repeat
      regions form a thermostable, alpha-helical trimer of heterodimers (S. B. Joshi,
      R. E. Dutch, and R. A. Lamb (1998). Virology 248, 20-34). Further
      characterization of the N-1/C-1 complex indicated that the C-1 peptides, which
      are predicted to residue on the outside of the complex, are resistant to
      digestion by several proteases when present in the complex. Only proteinase K
      digested most of the C-1 peptide, though the small remaining protease protected
      fragment of C-1 confers extreme thermostability on the proteinase-K-resistant N-1
      trimeric coiled-coil. Carboxypeptidase Y digestion of the N-1/C-1 complex
      indicates that the C-1 peptides associate in an antiparallel orientation relative
      to the N-1 peptides. Electron microscopy of the N-1/C-1 complex showed a rod
      shaped complex with an average length of 9.7 nm, consistent with all of N-1
      existing as an alpha helix. Mutations at heptad repeat a and d residues of N-1,
      positions that are predicted to point inward to the center of the N-1 trimeric
      coiled-coil, were found to have varying effects as analyzed by circular dichroism
      measurements. The mutation I137M did not affect the helical structure of the
      isolated N-1 peptide but did affect the thermostability of the N-1/C-1 complex.
      Mutations L140M and L161M perturbed the helical structure formed by N-1 in
      isolation but did not affect formation of a thermostable N-1/C-1 complex.
      Finally, a peptide, SV5 F 255-293, corresponding to a proposed leucine zipper
      region, was analyzed for effects on N-1, C-1, or the N-1/C-1 complex. Circular
      dichroism analysis demonstrated that while the presence of peptide 255-293
      increased the helical signal from either N-1 or the N-1/C-1 complex, no change in
      thermostability was observed, indicating that this region is not a component of
      the final, most stable core of the F protein.

PMID- 9927583
TI  - Complementarity between 3' terminal nucleotides of tRNA and primer binding site
      is a major determinant for selection of the tRNA primer used for initiation of
      HIV-1 reverse transcription.
AB  - The initiation of reverse transcription of human immunodeficiency virus type 1
      (HIV-1) exclusively utilizes tRNALys,3 as a primer. Previous studies have shown
      that HIV-1 could use alternative tRNAs, such as tRNAIle or tRNAHis, to initiate
      reverse transcription only if the primer binding site (PBS) was made
      complementary to the 3' terminal 18 nucleotides of the cognate tRNA. However,
      upon in vitro culture, the viruses with a PBS complementary to the alternative
      tRNAs rapidly reverted to generate a PBS complementary to tRNALys,3. To
      investigate the process of reversion, we have constructed defective proviral
      genomes that contain a PBS complementary to tRNAIle or tRNAHis. The genomes
      contain the gene for xanthine-guanosine phosphoribosyl transferase (gpt) in place
      of env. Cotransfection of these proviral genomes with a plasmid-encoding
      vesicular stomatitis virus G protein (VSV-G) results in viruses that undergo a
      single round of HIV-1 infection; successful infections are scored as cells
      resistant to the drug mycophenolic acid. Using this single-round infection
      system, we demonstrated that HIV-1 with a PBS complementary to tRNAIle or tRNAHis
      is three- to fivefold less efficient in replication as measured by production of
      drug-resistant cell colonies compared to the wild-type virus. These viruses
      predominantly used the cognate tRNA as primer in their initial round of
      replication, although we did obtain a single cell colony in which the PBS was
      complementary to tRNALys,3. Using an HIV-1 provirus with a PBS complementary to
      yeast tRNAPhe, we established a single-round infection system in which the
      infectivity of this mutant HIV-1 relies on transfected yeast tRNAPhe. The results
      of our studies suggest that the mechanism for selection of the tRNA primer for
      initiation of reverse transcription relies primarily on the complementarity
      between the tRNA primerthe PBS.

PMID- 9927584
TI  - Controlled conformational transitions in the MVM virion expose the VP1 N-terminus
      and viral genome without particle disassembly.
AB  - Antisera were raised against peptides corresponding to the N-termini of capsid
      proteins VP1 and VP2 from the parvovirus minute virus of mice. Epitopes in the
      142-amino-acid VP1-specific region were not accessible in the great majority of
      newly released viral particles, and sera directed against them failed to
      neutralize virus directly or deplete stocks of infectious virions. However, brief
      exposure to temperatures of 45 degreesC or more induced a conformational
      transition in a population of full virions, but not in empty viral particles, in
      which VP1-specific sequences became externally accessible. In contrast, the VP2 N
      terminus was antibody-accessible in all full, but not empty, particles without
      prior treatment. An electrophoretic mobility shift assay, in which particles were
      heat-treated and/or preincubated with antibodies prior to electrophoresis,
      confirmed this pattern of epitope accessibility, showing that the heat-induced
      conformational transition produces a retarded form of virion that can be
      supershifted by incubation with VP1-specific sera. The proportion of virions
      undergoing transition increased with temperature, but at all temperatures up to
      70 degreesC viral particles retained structure-specific antigenic determinants
      and remained essentially intact, without shedding individual polypeptide species
      or subunits. However, despite the apparent integrity of its protective coat, the
      genome became accessible to externally applied enzymes in an increasing
      proportion of virions through this temperature range, suggesting that the
      conformational transitions that expose VP1 likely also allow access to the
      genome. Heating particles to 80 degreesC or above finally induced disassembly to
      polypeptide monomers.

PMID- 9927585
TI  - Mechanism of interferon action: functional characterization of positive and
      negative regulatory domains that modulate transcriptional activation of the human
      RNA-dependent protein kinase Pkr promoter.
AB  - The PKR protein kinase is an important regulator of viral mRNA translation. A
      approximately 50-kb gene (Pkr) encodes the human PKR protein that is inducible by
      interferon (IFN). The Pkr promoter region has a novel 15-bp DNA element
      designated as KCS required for transcriptional activity that is located 4 bp
      upstream of a 13-bp IFN-stimulated response element (ISRE) that confers
      inducibility by type I IFN. We have carried out a systematic analysis of the 5'
      flanking region of the human Pkr gene to define how the novel KCS element acts to
      affect basal as well as IFN-inducible transcription. Electrophoretic mobility
      shift analyses (EMSA) revealed that nuclear proteins bound selectively to the KCS
      element in a manner that was not dependent upon either IFN treatment or protein
      binding at the adjacent ISRE element. KCS protein binding activity in vitro
      correlated with activation of transcription in vivo in transient transfection
      assays. Competitionsupershift EMSA assays revealed that multiple proteins were
      involved in bandshift complex formation with KCS, one of which was identified as
      factor Sp1. In addition to the positive regulatory domain containing the KCSISRE
      elements, a negative regulatory domain (NRD) was identified within a 40-bp region
      positioned approximately 400-bp upstream of the KCSISRE elements. Deletion and
      substitution mutations indicated that the NRD negatively affected Pkr
      transcription by a mechanism dependent upon the KCS element. These results define
      novel positivenegative regulatory domains within the Pkr promoter that function
      through the KCS element to affect basalIFN-inducible transcription of Pkr.

PMID- 9927586
TI  - The influenza virus M2 ion channel protein: probing the structure of the
      transmembrane domain in intact cells by using engineered disulfide cross-linking.
AB  - The influenza A virus M2 integral membrane protein is an ion channel that permits
      protons to enter virus particles during uncoating of virions in endosomes, and it
      also modulates the pH of the trans-Golgi network in virus-infected cells. M2
      protein is a homo-oligomer of 97 residues with a single transmembrane (TM) domain
      whose residues encompass the pore region of the channel and the biologically
      active form of the channel is a homotetramer. To understand the structural
      arrangement of the TM domains, each residue of the TM domain was changed in turn
      to cysteine, and oxidative disulfide cross-linking used to identify residues in
      close proximity. Oxidative treatment of M2 protein in membranes using iodine
      resulted in maximum cross-linking at TM domain residues 27, 34, and 41. Oxidation
      of M2 protein in membranes using the catalyst Cu(II)(1,10-phenanthroline)3
      resulted in cross-linking of many TM domain residues when the reaction was
      allowed to proceed at 37 degreesC, suggesting that rotational movements of the TM
      domains in the membrane can occur. However, analysis of the kinetics of disulfide
      linked dimer formation showed that TM domain residues 27, 30, 34, 37, and 41
      formed most rapidly. Furthermore, when oxidation was performed at 4 degreesC,
      maximum cross-linking occurred at TM domain residues 27, 30, 34, 37, and 41.
      These positions correspond to the a and d positions of a heptad repeat. Thus
      these biochemical data are consistent with the TM domain region of the M2
      tetramer forming a four-helix bundle. Analysis of the disulfide bonds that formed
      when oxidation of M2 protein in membranes was performed at pH 5.2 showed greatly
      reduced cross-linking at TM domain residues 40, 42, and 43 than that found at pH
      7.4. This pH-dependent change in cross-linking of residues toward the cytoplasmic
      side of the TM domain parallels with the activation of the M2 ion channel at low
      pH.

PMID- 9927587
TI  - Fossils, molecules and embryos: new perspectives on the Cambrian explosion.
AB  - The Cambrian explosion is named for the geologically sudden appearance of
      numerous metazoan body plans (many of living phyla) between about 530 and 520
      million years ago, only 1.7% of the duration of the fossil record of animals.
      Earlier indications of metazoans are found in the Neoproterozic; minute trails
      suggesting bilaterian activity date from about 600 million years ago. Larger and
      more elaborate fossil burrows appear near 543 million years ago, the beginning of
      the Cambrian Period. Evidence of metazoan activity in both trace and body fossils
      then increased during the 13 million years leading to the explosion. All living
      phyla may have originated by the end of the explosion. Molecular divergences
      among lineages leading to phyla record speciation events that have been earlier
      than the origins of the new body plans, which can arise many tens of millions of
      years after an initial branching. Various attempts to date those branchings by
      using molecular clocks have disagreed widely. While the timing of the evolution
      of the developmental systems of living metazoan body plans is still uncertain,
      the distribution of Hox and other developmental control genes among metazoans
      indicates that an extensive patterning system was in place prior to the Cambrian.
      However, it is likely that much genomic repatterning occurred during the Early
      Cambrian, involving both key control genes and regulators within their downstream
      cascades, as novel body plans evolved.

PMID- 9927588
TI  - Regulatory and functional interactions between the somatic sex regulatory gene
      transformer and the germline genes ovo and ovarian tumor.
AB  - In Drosophila, compatibility between the sexually differentiated state of the
      soma and the sex chromosome constitution of the germline is required for normal
      gametogenesis. In this study, we defined important aspects of the soma-germline
      interactions controlling early oogenesis. In particular, the sex-specific
      germline activity of the ovarian tumor promoter was found to be dependent upon
      somatic factors controlled by the somatic sex differentiation gene transformer.
      This regulation defines whether there is sufficient ovarian tumor expression in
      adult XX germ cells to support oogenesis. In addition, the ovarian tumor function
      required for female germline differentiation is dependent on the activity of
      another germline gene, ovo, whose regulation is transformer-independent. These
      and other data indicate that ovarian tumor plays a central role in coordinating
      regulatory inputs from the soma (as regulated by transformer) with those from the
      germline (involving ovo). We also demonstrate that transformer-dependent
      interactions influence whether XX germ cells require ovarian tumor or ovo
      functions to undergo early gametogenic differentiation. These results are
      incorporated into a model hypothesizing that the functions of ovarian tumor and
      ovo are dependent on an early sex determination decision in the XX germline that
      is at least partially controlled by somatic transformer activity.

PMID- 9927589
TI  - Similarity of DNA binding and transcriptional regulation by Caenorhabditis
      elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex
      determining mechanisms.
AB  - Although most animals occur in two sexes, the molecular pathways they employ to
      control sexual development vary considerably. The only known molecular similarity
      between phyla in sex determination is between two genes, mab-3 from C. elegans,
      and doublesex (dsx) from Drosophila. Both genes contain a DNA binding motif
      called a DM domain and they regulate similar aspects of sexual development,
      including yolk protein synthesis and peripheral nervous system differentiation.
      Here we show that MAB-3, like the DSX proteins, is a direct regulator of yolk
      protein gene transcription. We show that despite containing different numbers of
      DM domains MAB-3 and DSX bind to similar DNA sequences. mab-3 mutations
      deregulate vitellogenin synthesis at the level of transcription, resulting in
      expression in both sexes, and the vitellogenin genes have potential MAB-3 binding
      sites upstream of their transcriptional start sites. MAB-3 binds to a site in the
      vit-2 promoter in vitro, and this site is required in vivo to prevent
      transcription of a vit-2 reporter construct in males, suggesting that MAB-3 is a
      direct repressor of vitellogenin transcription. This is the first direct link
      between the sex determination regulatory pathway and sex-specific structural
      genes in C. elegans, and it suggests that nematodes and insects use at least some
      of the same mechanisms to control sexual development.

PMID- 9927591
TI  - Induction of the epibranchial placodes.
AB  - The cranial sensory ganglia, in contrast to those of the trunk, have a dual
      embryonic origin arising from both neurogenic placodes and neural crest.
      Neurogenic placodes are focal thickenings of ectoderm, found exclusively in the
      head of vertebrate embryos. These structures can be split into two groups based
      on the positions that they occupy within the embryo, dorsolateral and
      epibranchial. The dorsolateral placodes develop alongside the central nervous
      system, while the epibranchial placodes are located close to the top of the
      clefts between the branchial arches. Importantly, previous studies have shown
      that the neurogenic placodes form under the influence of the surrounding cranial
      tissues. In this paper, we have analysed the nature of the inductive signal
      underlying the formation of the epibranchial placodes. We find that epibranchial
      placodes do not require neural crest for their induction, but rather that it is
      the pharyngeal endoderm that is the source of the inductive signal. We also find
      that, while cranial ectoderm is competent to respond to this inductive signal,
      trunk ectoderm is not. We have further identified the signalling molecule Bmp7 as
      the mediator of this inductive interaction. This molecule is expressed in a
      manner consistent with it playing such a role and, when added to ectoderm
      explants, it will promote the formation of epibranchial neuronal cells. Moreover,
      the Bmp7 antagonist follstatin will block the ability of pharyngeal endoderm to
      induce placodal neuronal cells, demonstrating that Bmp7 is required for this
      inductive interaction. This work answers the long standing question regarding the
      induction of the epibranchial placodes, and represents the first elucidation of
      an inductive mechanism, and a molecular effector, underlying the formation of any
      primary sensory neurons in higher vertebrates.

PMID- 9927590
TI  - BMPs negatively regulate structure and function of the limb apical ectodermal
      ridge.
AB  - The apical ectodermal ridge (AER), a transient specialized epithelium at the
      distal limb tip, is essential for vertebrate embryonic limb outgrowth along the
      proximodistal axis. Among all the molecules expressed in the AER, only the
      Fibroblast Growth Factors (FGFs) have been shown to substitute for its function
      in limb outgrowth. After specification of the skeletal progenitors is complete,
      the AER regresses, having fulfilled its function. However, the cellular processes
      underlying AER regression remain largely unclear, and the molecular ones, totally
      unknown. Members of the Bone Morphogenetic Protein (BMP) family are expressed in
      the AER throughout its life and in the mesenchyme. Our studies using
      misexpression of Noggin, a BMP inhibitor, reveal an unsuspected role for BMPs in
      the negative regulation of Fgf expression and AER function. We find that BMPs
      limit limb outgrowth by promoting AER regression, as BMP inhibition results in
      persistence of the AER, prolonged Fgf expression and excess soft-tissue growth.
      In addition, the Noggin misexpression studies uncover an earlier role for BMPs in
      repression of AER function. Noggin overexpression results in extension of the AER
      anteriorly and loss of AER asymmetry. We show that overall the AER becomes
      taller, and its anterior half becomes more similar to a normal posterior AER. In
      addition, Fgf4 transcripts, which are usually restricted to the posterior half of
      the AER, are now also expressed anteriorly. Moreover, ectopicFgf4 expression is
      induced independently of Sonic Hedgehog, contrary to current models of Fgf4
      regulation in the limb. Our studies also provide insight into the activity of the
      hypothesized apical ectodermal maintenance factor (AEMF), which is thought to
      maintain the tall shape of the posterior part of the AER. Our work shows that the
      AER is negatively regulated by BMP.

PMID- 9927592
TI  - Extracellular proteolysis alters tooth development in transgenic mice expressing
      urokinase-type plasminogen activator in the enamel organ.
AB  - By catalyzing plasmin formation, the urokinase-type plasminogen activator (uPA)
      can generate widespread extracellular proteolysis and thereby play an important
      role in physiological and pathological processes. Dysregulated expression of uPA
      during organogenesis may be a cause of developmental defects. Targeted epithelial
      expression of a uPA-encoding transgene under the control of the keratin type-5
      promoter resulted in enzyme production by the enamel epithelium, which does not
      normally express uPA, and altered tooth development. The incisors of transgenic
      mice were fragile, chalky-white and, by scanning electron microscopy, their
      labial surface appeared granular. This phenotype was attributed to a defect in
      enamel formation during incisor development, resulting from structural and
      functional alterations of the ameloblasts that differentiate from the labial
      enamel epithelium. Immunofluorescence revealed that disorganization of the
      ameloblast layer was associated with a loss of laminin-5, an extracellular matrix
      molecule mediating epithelial anchorage. Amelogenin, a key protein in enamel
      formation, was markedly decreased at the enamel-dentin junction in transgenics,
      presumably because of an apparent alteration in the polarity of its secretion. In
      addition, increased levels of active transforming growth factor-beta could be
      demonstrated in mandibles of transgenic mice. Since the alterations detected
      could be attributed to uPA catalytic activity, this model provides evidence as to
      how dysregulated proteolysis, involving uPA or other extracellular proteases, may
      have developmental consequences such as those leading to enamel defects.

PMID- 9927593
TI  - The vestigial gene product provides a molecular context for the interpretation of
      signals during the development of the wing in Drosophila.
AB  - The vestigial (vg) gene of Drosophila plays a central role in the development and
      patterning of the wing: loss of vestigial results in failures in wing development
      and ectopic expression of vestigial leads to the development of ectopic wings.
      The wing-specific regulation of vestigial is mediated through two enhancers: (1)
      the Boundary Enhancer (vgBE) is early acting and becomes restricted to the wing
      margin, and (2) the Quadrant Enhancer (vgQE), acts later and is responsible for
      the expression of vestigial in the developing wing blade. These enhancers receive
      regulatory inputs from three signalling pathways: wingless, decapentaplegic and
      Notch/Suppressor of Hairless. Our experiments show that the vestigial gene
      product is also an input in the regulation of vestigial expression. In
      particular, Vestigial provides an important input for the regulation of the
      activity of the vgQE acting in concert with Wingless and Decapentaplegic. Our
      results suggest how interactions between vgBE and the vgQE mediated by Vestigial
      can explain the interactions between the wing margin and the wing blade during
      the growth of the wing. We further show that Vestigial and Notch collaborate with
      Wingless to subdivide and pattern the wing blade. These results lead us to
      propose a general role for Wingless during development in which it stabilizes
      cell fate decisions that have been implemented by other molecules.

PMID- 9927594
TI  - Binuclear Drosophila oocytes: consequences and implications for dorsal-ventral
      patterning in oogenesis and embryogenesis.
AB  - The position of the nucleus along the anterior rim of stage 8 Drosophila oocytes
      presages the dorsal side of the egg and the developing embryo. In this paper, we
      address the question of whether the oocyte has a previously determined dorsal
      side to which the nucleus is drawn, or whether nuclear position randomly
      determines the dorsal side. To do so, we have taken advantage of a genetic system
      in which Drosophila oocytes occasionally become binuclear. We find that (i) the
      two nuclei migrate independently to their respective positions on the anterior
      rim, sometimes selecting the same site, sometimes not, (ii) the two nuclei are
      equivalent in their ability to induce a dorsal-ventral pattern in the overlying
      follicular epithelium, and (iii) at any position around the anterior
      circumference of the egg chamber the follicle cell sheet is equally responsive to
      the Gurken signal associated with the oocyte nuclei. These results argue that the
      dorsal-ventral axis is determined arbitrarily by the randomly selected position
      of the nucleus on the anterior rim of the oocyte. Some of the binuclear eggs
      support embryonic development. However, despite the duplication of dorsal chorion
      structures, the majority of such embryos show normal dorsal-ventral patterning.
      Thus, processes exist in the ventral follicular epithelium or in the
      perivitelline space that compensate for the expansion of dorsal follicle cell
      fates and consequently allow the formation of a normal embryonic axis.

PMID- 9927595
TI  - Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within
      the network of genes controlling retinal cell fate determination in Drosophila.
AB  - Retinal cell fate determination in Drosophila is controlled by an interactive
      network of genes, including eyeless, eyes absent, sine oculis and dachshund. We
      have investigated the role of the TGF-beta homolog decapentaplegic in this
      pathway. We demonstrate that, during eye development, while eyeless transcription
      does not depend on decapentaplegic activity, the expression of eyes absent, sine
      oculis and dachshund are greatly reduced in a decapentaplegic mutant background.
      We also show that decapentaplegic signaling acts synergistically with and at
      multiple levels of the retinal determination network to induce eyes absent, sine
      oculis and dachshund expression and ectopic eye formation. These results suggest
      a mechanism by which a general patterning signal such as Decapentaplegic
      cooperates reiteratively with tissue-specific factors to determine distinct cell
      fates during development.

PMID- 9927596
TI  - Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of
      the midbrain.
AB  - Experiments involving tissue recombinations have implicated both early vertical
      and later planar signals in the specification and polarisation of the midbrain.
      Here we investigate the role of fibroblast growth factors in regulating these
      processes in the avian embryo. We show that Fgf4 is expressed in the notochord
      anterior to Hensen's node before transcripts for the earliest molecular marker of
      midbrain tissue in the avian embryo, En1, are detected. The presence of notochord
      is required for the expression of En1 in neural plate explants in vitro and FGF4
      mimics this effect of notochord tissue. Subsequently, a second member of the
      fibroblast growth factor family, Fgf8, is expressed in the isthmus in a manner
      consistent with it providing a polarising signal for the developing midbrain.
      Using a retroviral vector to express En1 ectopically, we show that En1 can induce
      Fgf8 expression in midbrain and posterior diencephalon. Results of the
      introduction of FGF8 protein into the anterior midbrain or posterior diencephalon
      are consistent with it being at least part of the isthmic activity which can
      repolarise the former tissue and respecify the latter to a midbrain fate.
      However, the ability of FGF8 to induce expression of genes which have earlier
      onsets of expression than Fgf8 itself, namely En1 and Pax2, strongly suggests
      that the normal function of FGF8 is in maintaining patterns of gene expression in
      posterior midbrain. Finally, we provide evidence that FGF8 also provides
      mitogenic stimulation during avian midbrain development.

PMID- 9927597
TI  - Delta1 expression during avian hair cell regeneration.
AB  - Postembryonic production of hair cells, the highly specialized receptors for
      hearing, balance and motion detection, occurs in a precisely controlled manner in
      select species, including avians. Notch1, Delta1 and Serrate1 mediate cell
      specification in several tissues and species. We examined expression of the
      chicken homologs of these genes in the normal and drug-damaged chick inner ear to
      determine if signaling through this pathway changes during hair cell
      regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a
      subpopulation of cells in the utricle, which undergoes continual postembryonic
      hair cell production, but it is absent from all cells in the basilar papilla,
      which is mitotically quiescent. By 3 days after drug-induced hair cell injury,
      Delta1 expression is highly upregulated in areas of cell proliferation in both
      the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor
      cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression
      is maintained in both daughter cells immediately after mitosis. Delta1 expression
      remains upregulated in cells that differentiate into hair cells and is
      downregulated in cells that do not acquire the hair cell fate. Delta1 mRNA levels
      return to normal by 10 days after hair cell injury. Serrate1 is expressed in both
      hair cells and support cells in the utricle and basilar papilla, and its
      expression does not change during the course of drug-induced hair cell
      regeneration. In contrast, Notch1 expression, which is limited to support cells
      in the quiescent epithelium, is increased in post-M-phase cell pairs during hair
      cell regeneration. This study provides initial evidence that Delta-Notch
      signaling may be involved in maintaining the correct cell types and patterns
      during postembryonic replacement of sensory epithelial cells in the chick inner
      ear.

PMID- 9927598
TI  - Role of the EGF receptor pathway in growth and patterning of the Drosophila wing
      through the regulation of vestigial.
AB  - Growth and patterning of the Drosophila wing disc depends on the coordinated
      expression of the key regulatory gene vestigial both in the Dorsal-Ventral (D/V)
      boundary cells and in the wing pouch. We propose that a short-range signal
      originating from the core of the D/V boundary cells is responsible for activating
      EGFR in a zone of organizing cells on the edges of the D/V boundary. Using loss
      of-function mutations and ectopic expression studies, we show that EGFR signaling
      is essential for vestigial transcription in these cells and for making them
      competent to undergo subsequent vestigial-mediated proliferation within the wing
      pouch.

PMID- 9927599
TI  - Delta-1 negatively regulates the transition from prehypertrophic to hypertrophic
      chondrocytes during cartilage formation.
AB  - Endochondral bone development begins with the formation of a cartilage template.
      Chondrocytes within this template undergo a progressive program of maturation
      from proliferative to prehypertrophic chondrocytes to hypertrophic chondrocytes.
      The progression of cells through these steps of differentiation must be carefully
      controlled to ensure coordinated growth. Because the Delta/Notch signaling system
      is known to regulate cell fate choices, we sought to determine if these molecules
      might be involved in the progressive cell fate decisions that chondocytes
      undergo. Here we demonstrate in the chick that Delta/Notch signaling negatively
      regulates progression from the prehypertrophic to hypertrophic state of
      differentiation. Delta-1 is expressed specifically in the hypertrophic
      chondrocytes while Notch-2 is expressed in chondrocytes at all stages.
      Misexpression of Delta-1 using a replication-competent retrovirus blocks
      chondrocyte maturation. Prehypertrophic cells form normally but do not undergo
      differentiation to hypertrophic cells, resulting in shortened skeletal elements
      that lack ossification. We conclude that Delta-1 acts during chondrogenesis to
      inhibit the transition from prehypertrophic chondrocytes to hypertrophic
      chondrocytes, thus defining a novel mechanism for the regulation of the
      chondrocyte maturation program. In addition, these results reveal a new role for
      Delta/Notch signaling in regulating the progression to a terminally
      differentiated state.

PMID- 9927601
TI  - Genetic control of programmed cell death in the Caenorhabditis elegans
      hermaphrodite germline.
AB  - Development of the nematode Caenorhabditis elegans is highly reproducible and the
      fate of every somatic cell has been reported. We describe here a previously
      uncharacterized cell fate in C. elegans: we show that germ cells, which in
      hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic
      cell death. In adult hermaphrodites, over 300 germ cells die, using the same
      apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously
      described 131 somatic cell deaths. However, this machinery is activated by a
      distinct pathway, as loss of egl-1 function, which inhibits somatic cell death,
      does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway
      activation and is used to maintain germline homeostasis. We suggest that
      apoptosis eliminates excess germ cells that acted as nurse cells to provide
      cytoplasmic components to maturing oocytes.

PMID- 9927600
TI  - HyBra1, a Brachyury homologue, acts during head formation in Hydra.
AB  - A homologue of the T-box gene, Brachyury, has been isolated from hydra. The gene,
      termed HyBra1, is expressed in the endoderm and is associated with the formation
      of the hypostome, the apical part of the head in four different developmental
      situations. In adults, which are continuously undergoing patterning, HyBra1 is
      continuously expressed in the hypostome. During budding, hydra's asexual form of
      reproduction, the gene is expressed in a small area that will eventually form the
      hypostome of the developing bud before any morphological sign of budding is
      apparent. The gene is also expressed very early during head regeneration and is
      confined to the region that will form the hypostome. During embryogenesis, HyBra1
      is expressed shortly before hatching in the region that will form the apical end
      of the animal, the hypostome. The absence of expression at the apical end of
      decapitated animals of reg-16, a head formation-deficient mutant, provides
      additional evidence for a role of HyBra1 during head formation. Further,
      treatments that alter the head activation gradient have no effect on HyBra1
      expression indicating the role of the gene is confined to head formation.
      Transplantation experiments indicate that the expression occurs before head
      determination has occurred, but expression does not irreversibly commit tissue to
      forming a head. A comparison of the function of the Brachyury homologues suggests
      an evolutionary conservation of a molecular mechanism that has been co-opted for
      a number of developmental processes throughout evolution.

PMID- 9927602
TI  - Induction of indora expression in pole cells by the mesoderm is required for
      female germ-line development in Drosophila melanogaster.
AB  - In many animal groups, the interaction between germ and somatic line is required
      for germ-line development. In Drosophila, the germ-line precursors (pole cells)
      formed at the posterior tip of the embryos migrate toward the mesodermal layer
      where they adhere to the dorsolateral mesoderm, which ensheaths the pole cells to
      form the embryonic gonads. These mesodermal cells may control the expression of
      genes that function in pole cells for their development into germ cells. However,
      such downstream genes have not been isolated. In this study, we identify a novel
      transcript, indora (idr), which is expressed only in pole cells within the
      gonads. Reduction of idr transcripts by an antisense idr expression caused the
      failure of pole cells to produce functional germ cells in females. Furthermore,
      we demonstrate that idr expression depends on the presence of the dorsolateral
      mesoderm, but it does not necessarily require its specification as the gonadal
      mesoderm. Our findings suggest that the induction of idr in pole cells by the
      mesodermal cells is required for germ-line development.

PMID- 9927603
TI  - The role of dorsoventral interaction in the onset of planarian regeneration.
AB  - During planarian regeneration, dorsal and ventral tissues adhere to each other as
      a result of wound closure. To investigate the role of dorsoventral (DV)
      interaction in regeneration, dorsal and ventral portions were ectopically
      reoriented relative to each other by grafting. We sucked a small piece of
      planarian body into a Pasteur pipette, and then grafted the piece to the original
      position in DV-reversed orientation. 4 days after grafting, a blastema-like white
      region was formed on the boundary between the host and the graft. The region grew
      and formed a cup-shaped projection on both the dorsal and ventral sides of the
      worm after about 1 week. Histological analysis and in situ hybridization using
      dorsal and ventral markers revealed that the grafted piece maintained its
      original DV polarity. Analysis using DV boundary markers clearly indicated that a
      DV axis was newly established within the projection. Chimeric analysis using a
      strain-specific marker demonstrated that the projection grew on the DV boundary.
      Further analysis, using a marker specific for neoblasts and differentiating
      cells, showed that the projection was composed of neoblasts and/or neoblast
      derived cells. Thus, ectopic DV interaction can cause blastema formation,
      outgrowth and establishment of a DV axis. In addition, staining with tissue- and
      region-specific markers showed that the projection appears to be identical to the
      structure from the grafted position to the most anterior or posterior tip. These
      results suggest that DV interaction evoked by wound closure has a important role
      in the onset of regeneration, especially for blastema formation and establishment
      of the DV axis during planarian regeneration.

PMID- 9927604
TI  - A molecular mechanism enabling continuous embryonic muscle growth - a balance
      between proliferation and differentiation.
AB  - Embryonic muscle growth requires a fine balance between proliferation and
      differentiation. In this study we have investigated how this balance is achieved
      during chick development. Removal of ectoderm from trunk somites results in the
      down-regulation of Pax-3 expression and cell division of myogenic precursors is
      halted. This initially leads to an up-regulation of MyoD expression and to a
      burst in terminal differentiation but further muscle growth is arrested. Locally
      applied bone morphogenetic protein-4 (BMP-4) to somites mimics the effect of the
      ectoderm and stimulates Pax-3 expression which eventually results in excessive
      muscle growth in somites. Surprisingly, BMP-4 up-regulates expression of noggin
      which encodes a BMP-4 antagonist. This suggests that the proliferation enhancing
      activity of BMP-4 can be limited via up-regulation of noggin and that myogenic
      cells differentiate, as an intrinsic property, when deprived of BMP-4 influence.
      In contrast to BMP-4, Sonic hedgehog (Shh) locally applied to somites arrests
      muscle growth by down-regulation of Pax-3 and immediate up-regulation of MyoD
      expression. Such premature muscle differentiation in somites at tongue and limb
      levels prevents myogenic migration and thus tongue and limb muscle are not
      formed. Therefore, precise limitation of differentiation, executed by
      proliferative and Pax-3 promoting signals, is indispensable for continuous
      embryonic muscle growth.

PMID- 9927605
TI  - EGL-27 is similar to a metastasis-associated factor and controls cell polarity
      and cell migration in C. elegans.
AB  - Mutations in the C. elegans gene egl-27 cause defects in cell polarity and cell
      migration: the polarity of the asymmetric T cell division is disrupted and the
      descendants of the migratory QL neuroblast migrate incorrectly because they fail
      to express the Hox gene mab-5. Both of these processes are known to be controlled
      by Wnt pathways. Mosaic analysis indicates that egl-27 function is required in
      the T cell for proper cell polarity. We cloned egl-27 and discovered that a
      domain of the predicted EGL-27 protein has similarity to Mta1, a mammalian factor
      overexpressed in metastatic cells. Overlaps in the phenotypes of egl-27 and Wnt
      pathway mutants suggest that the EGL-27 protein interacts with Wnt signaling
      pathways in C. elegans.

PMID- 9927606
TI  - Expression of the cell cycle in sperm of Arabidopsis: implications for
      understanding patterns of gametogenesis and fertilization in plants and other
      eukaryotes.
AB  - The relationship between developmental events and the cell cycle was examined in
      sperm of Arabidopsis thaliana. Sperm of Arabidopsis rapidly enter the S
      (synthesis) phase of the cell cycle after inception from mitosis of the
      generative cell. Sperm in pollen grains within anthers continue to synthesize
      DNA, and at the time of pollination, contain approximately 1.5C DNA. Following
      pollination, sperm continue through the S phase of the cell cycle during pollen
      tube growth. By the time pollen tubes reach the ovary, sperm nuclei contain
      approximately 1.75C DNA. Just prior to double fertilization, sperm nuclei within
      embryo sacs contain the 2C quantity of DNA. These data indicate that molecular
      programs associated with the G1-S transition and the S phase of the cell cycle
      are expressed in sperm cells of developing pollen grains and pollen tubes in
      Arabidopsis. This pattern of prefertilization S phase activity in the sperm of a
      flowering plant stands in marked contrast to all other non-plant eukaryotes (from
      ciliates to yeast to sea urchins to mammals) where sperm remain in G1 during
      development, prior to the initiation of gametic fusion. In addition, when
      patterns of cell cycle activity in sperm of Arabidopsis and other flowering
      plants are compared, developmental analysis reveals that heterochronic
      alterations (changes in the relative timing of ontogenetic events) in cell cycle
      activity are a central cause of the diversification of patterns of gametogenesis
      in higher plants. Finally, comparative analysis of the patterns of cell cycle
      activity in Arabidopsis and other angiosperms may be used to predict which
      flowering plants will be amenable to development of successful in vitro
      fertilization techniques.

PMID- 9927607
TI  - Neurotransmitter receptor activation triggers p27(Kip1 )and p21(CIP1)
      accumulation and G1 cell cycle arrest in oligodendrocyte progenitors.
AB  - We examined the pathways that link neurotransmitter receptor activation and cell
      cycle arrest in oligodendrocyte progenitors. We had previously demonstrated that
      glutamate receptor activation inhibits oligodendrocyte progenitor proliferation
      and lineage progression. Here, using purified oligodendrocyte progenitors and
      cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic
      receptor agonist isoproterenol also inhibited the proliferation, but in contrast
      to glutamate, isoproterenol stimulated progenitor lineage progression, as
      determined by O4 and O1 antibody staining. This antiproliferative effect was
      specifically attributable to a beta-adrenoceptor-mediated increase in cyclic
      adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the
      effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha
      adrenoceptor agonists were ineffective. Despite the opposite effects on lineage
      progression, both isoproterenol and the glutamate receptor agonist kainate caused
      accumulation of the cyclin-dependent kinase inhibitors p27(Kip1)and p21(CIP1),
      and G1 arrest. Studies with oligodendrocyte progenitor cells from INK4a-/- mice
      indicated that the G1 cyclin kinase inhibitor p16(INK4a) as well as p19(ARF)were
      not required for agonist-stimulated proliferation arrest. Our results demonstrate
      that beta-adrenergic and glutamatergic receptor activation inhibit
      oligodendrocyte progenitor proliferation through a mechanism that may involve
      p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of
      p27(Kip1) is associated with cell cycle arrest, it does not by itself promote
      oligodendrocyte progenitor differentiation.

PMID- 9927608
TI  - Modulation of relative intrinsic activity of agonists at the alpha-2A
      adrenoceptor by mutation of residue 351 of G protein gi1alpha.
AB  - Compared with epinephrine, the relative intrinsic activity of a series of partial
      agonists to activate fusion proteins between the porcine alpha-2A adrenoceptor
      and the alpha-subunit of Gi1 was reduced after a single-point mutation
      (Cys351Gly) in the G protein. Although UK14304 was close to a full agonist at the
      fusion construct containing wild-type (Cys351)Gi1alpha, it was a partial agonist
      at that containing Gly351Gi1alpha. Moreover, although clonidine functioned as a
      good partial agonist to activate the fusion protein containing Cys351Gi1alpha, it
      was essentially an antagonist at the Gly351Gi1alpha-containing fusion protein. By
      contrast, incorporation of Ile351Gi1alpha into the fusion protein resulted in all
      partial agonists displaying higher intrinsic activity relative to epinephrine to
      activate this fusion protein than the one containing the wild-type G protein
      sequence. This is the first demonstration that the relative intrinsic activity of
      a series of agonists can be modified by a point mutation in a G protein rather
      than a receptor and indicates that the nature of a key contact site between a G
      protein and a receptor can selectively regulate partial agonist function. We
      provide a model for this based on the hydrophobicity of a key receptor-G protein
      alpha-subunit interaction interface.

PMID- 9927610
TI  - Pivotal role of an aspartate residue in sodium sensitivity and coupling to G
      proteins of neurotensin receptors.
AB  - The highly conserved aspartate residue in the second transmembrane domain of G
      protein-coupled receptors is present in position 113 in the type 1 neurotensin
      receptor (NTR1) but is replaced by an Ala residue in position 79 in the type 2
      neurotensin receptor (NTR2). NTR1 couples to Galphaq to stimulate phospholipase C
      and its binding affinity for neurotensin is decreased by sodium ions and GTP
      analogs. By contrast, NTR2 does not seem to couple to any G protein in eukaryotic
      cells, and its binding of neurotensin is insensitive to sodium and GTP analogs.
      By using site-directed mutagenesis, we substituted Asp113 of the NTR1 by alanine
      and the homologous residue Ala79 of NTR2 by aspartate. Both mutant receptors
      display similar affinity for neurotensin as compared with their respective wild
      type. We demonstrate that the presence of the Asp residue determines by itself
      the occurrence of the sodium effect on neurotensin affinity for both wild-type
      and mutated NTR1 and -2. The introduction of an Asp in the second transmembrane
      domain of NTR2 is not enough to restore a functional coupling to G proteins. In
      contrast, replacement of Asp113 by Ala residue in NTR1 strongly decreases its
      ability to activate inositol turnover, indicating that the functionally active
      conformation of NTR1 is maintained by interaction of sodium ions with aspartate
      113.

PMID- 9927609
TI  - Increased site-specific phosphorylation of tyrosine hydroxylase accompanies
      stimulation of enzymatic activity induced by cessation of dopamine neuronal
      activity.
AB  - Activation of striatal dopamine (DA) neurons by neuroleptic treatment or by
      electrical stimulation of the nigrostriatal pathway increases the activity of
      tyrosine hydroxylase (TH). The increase is mediated by phosphorylation of the
      enzyme. However, abolition of DA neuronal activity [by gamma-butyrolactone (GBL)
      treatment or transection of the nigrostriatal pathway] also increases TH
      activity. Quantitative blot immunolabeling experiments using site- and
      phosphorylation state-specific antibodies to TH demonstrated that GBL treatment
      (750 mg/kg, 35 min) significantly increased phosphorylation at Ser19 (+40%) and
      Ser40 (+217%) without altering Ser31 phosphorylation. Concomitantly, GBL
      treatment [along with the 3,4-dihydroxyphenylalanine (dopa) decarboxylase
      inhibitor NSD-1015, 100 mg/kg, 30 min] increased in vivo striatal dopa
      accumulation and in vitro TH activity 3-fold. Likewise, cerebral hemitransection
      of the nigrostriatal pathway significantly increased phosphorylation of TH at
      Ser19 (+89%) and Ser40 (+158%) but not at Ser31; dopa levels were increased
      accordingly (+191%). Kinetic analysis of TH activity established that GBL
      treatment and hemitransection primarily decreased the Km for the cofactor
      tetrahydrobiopterin (3-fold). The effects of GBL and hemitransection were
      abolished or attenuated by pretreatment with the DA agonist R-(-)-N-n
      propylnorapomorphine (NPA; 30 microgram/kg, 40 min), presumably via stimulation
      of inhibitory presynaptic DA autoreceptors. NPA dose-response curves for reversal
      of GBL-induced dopa accumulation and Ser40 phosphorylation were identical;
      however, only the highest dose of NPA reversed the small and variable increase in
      Ser19 phosphorylation. Thus, TH activity seems to be regulated by phosphorylation
      in both hyper- and hypoactive striatal DA neurons; in the latter case, activation
      seems to be caused by selective phosphorylation of Ser40.

PMID- 9927611
TI  - DNA damage signals induction of fas ligand in tumor cells.
AB  - Many anticancer agents exert their cytotoxicity through DNA damage and induction
      of apoptosis. Fas ligand (FasL), a key component of T lymphocytes, has been shown
      to be induced by some of those agents. To address what is an early signal for
      this induction, we constructed a FasL promoter-luciferase reporter gene to
      investigate effects of DNA topoisomerase (Topo) II inhibitors on FasL promoter
      activity. Transient transfection assays in HeLa and other tumor cell lines
      demonstrated that induction of FasL promoter activity in response to Topo II
      inhibitors such as VM-26 mimicked endogenous FasL expression under the same
      conditions. The ability of these agents to induce FasL expression correlated with
      their ability to cause DNA damage. For instance, complex-stabilizing Topo II
      inhibitors such as etoposide, teniposide, and doxorubicin, which cause DNA
      damage, strongly induce FasL expression; by contrast, non-DNA-damaging catalytic
      Topo II inhibitors such as ICRF-187 and merbarone do not do this. In support of
      the notion that DNA damage triggers FasL induction, we found that DNA-damaging
      irradiation also induced FasL promoter activity in a dose-dependent manner.
      Finally, the catalytic Topo II inhibitor ICRF-187 suppressed VM-26-induced-FasL
      expression. This suppression correlated with the ability of this drug to inhibit
      VM-26-induced DNA strand breaks. Together, our results suggest that DNA damage in
      response to agents such as etoposide and teniposide might serve as an early
      signal to induce FasL expression.

PMID- 9927612
TI  - Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics.
AB  - Autoantibodies against soluble liver enzymes have been reported among alcoholics,
      but the targets of self-reactivity toward membrane proteins of the liver have not
      been characterized. Previously, among alcoholics, we found antibodies against
      ethanol-derived radical protein adducts that are dependent on cytochrome P-4502E1
      (CYP2E1) for their formation. To further investigate autoantibodies against
      cytochrome P-450s during alcohol abuse, sera of rats chronically treated with
      ethanol in the total enteral nutrition model and sera from alcoholics with or
      without alcohol liver disease and from control subjects were analyzed by enzyme
      linked immunosorbent assay and Western blotting for the presence of IgG against
      rat and human CYP2E1, rat CYP3A1, and human CYP3A4. A time-dependent appearance
      of IgG against rat CYP3A1 and CYP2E1 was evident during chronic ethanol feeding
      of rats. Anti-CYP2E1 reactivity showed positive correlation with the levels of
      hepatic CYP2E1 and was inhibited by the CYP2E1 transcriptional inhibitor
      chlormethiazole. Screening of the human sera by enzyme-linked immunosorbent assay
      revealed reactivity against CYP3A4 and CYP2E1 in about 20 to 30% and 10 to 20% of
      the alcoholic sera, respectively. No difference were noted between sera from
      alcoholics with or without hepatitis C virus infection, and only very little
      reactivity was seen in sera from control subjects. Western blotting analysis
      revealed anti-human CYP2E1 reactivity in 8 of 85 alcoholic sera and 3 of 58
      control sera, whereas anti-CYP3A4 reactivity was detected in 18 of 85 alcoholic
      sera and 4 of 58 control sera, which were different from the sera reactive with
      CYP2E1. Immunoblot reactivity of CYP3A4-positive alcoholic sera was found against
      glutathione-S-transferase fusion proteins containing truncated forms of CYP3A4,
      and such sera were also able to immunoprecipitate in vitro translated CYP3A4.
      Seven of eight sera showed reactivity toward domains C-terminal of position
      Ser281, and 1 of 8 sera recognized autoepitopes within the region Thr207-Ser281.
      These findings indicate that alcoholics develop autoantibodies against CYP2E1 and
      CYP3A4 that the CYP3A4 C-terminal domain is a target for the autoantibody
      reactions among a subset of alcoholics. The novel finding of CYP3A4
      autoantibodies and their significant expression among alcoholics warrants further
      investigation. Attention should be given to immune toxicity associated with
      CYP3A4 autoantibodies and cases of alcohol abuse that are accompanied by exposure
      to drugs and substances that are CYP3A substrates.

PMID- 9927613
TI  - Characterization of a bioengineered chimeric Na+-nucleoside transporter.
AB  - Na+-dependent nucleoside transporters mediate the intracellular uptake of purine
      and pyrimidine nucleosides. The N1, N2, and N3 Na+-nucleoside transporters differ
      in substrate selectivity. N1 is purine-selective, N2 is pyrimidine-selective, and
      N3 is broadly selective. Recently, we created a chimeric transporter, T8, from
      the cloned rat N1 and N2 transporters. Whereas most chimeric proteins exhibit the
      characteristics of one of the two parent proteins, limited studies suggested that
      T8 possesses either a combined substrate selectivity of N1 and N2 or the
      selectivity of N3. The purpose of this study was to determine the substrate
      profile, transport mechanisms, and Na+-coupling stoichiometry of T8 and to
      compare these measurements with those of wild-type N1, N2, and N3. In Xenopus
      laevis oocytes expressing T8, Na+-dependent uptake of 3H-labeled purine
      (adenosine, inosine, and guanosine) and pyrimidine nucleosides (uridine,
      thymidine, and cytidine) was significantly enhanced (3.5-18.6-fold), which
      suggests that T8 accepts both purine and pyrimidine nucleosides as permeants. T8
      mediated uptake of [3H]thymidine was competitively inhibited by inosine, and T8
      mediated uptake of [3H]inosine was competitively inhibited by thymidine, which
      suggests that purine and pyrimidine nucleosides share a common binding site. Base
      modified ribo- and 2'-deoxyribonucleosides were potent inhibitors of T8. In
      contrast, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, and 3'-azidothymidine,
      which are known inhibitors of N1 or N2, did not inhibit T8-mediated uptake. These
      data suggest that the substrate profile of T8 is not a combination of those of N1
      and N2; rather, it is similar to that of N3. However, the Na+/nucleoside
      stoichiometric ratio of T8 was determined to be 1, consistent with both N1 and N2
      but different from N3.

PMID- 9927614
TI  - Use of chimeric enzymes and site-directed mutagenesis for identification of three
      key residues responsible for differences in steroid hydroxylation between canine
      cytochromes P-450 3A12 and 3A26.
AB  - Canine cytochromes P-450 3A12 and 3A26 differ by 22 out of 503 amino acid
      residues. Chimeric constructs and site-directed mutants were used to identify the
      residues responsible for the much higher rates of steroid hydroxylation by 3A12.
      Six initial 3A12/3A26 hybrids were generated using convenient restriction sites,
      and site-directed mutagenesis was used to restore full 3A12 activity to two of
      the hybrids. One pair of 3A12/3A26 chimeras indicated that the first four residue
      differences between 3A12 and 3A26 were at least partially responsible for the
      differences in progesterone hydroxylation. Conversion in one of the hybrids of
      the Ile-187 residue found in 3A26 to the Thr in 3A12 conferred 3A12 levels of
      progesterone 6beta-hydroxylase activity. Analysis of another chimera identified
      key residues within an internal PstI fragment (codons 331-459) containing six
      amino acid residue differences. Subsequent site-directed mutagenesis of 3A26
      residues Ser-368 and Val-369 to Pro and Ile, respectively, restored the rate of
      formation of 6beta-hydroxyprogesterone by the hybrid to that of 3A12. The
      simultaneous conversion of 3A26 residues 187, 368, and 369 to those of 3A12
      conferred greater than a third of the progesterone 6beta-hydroxylase activity and
      all of the testosterone and androstenedione 6beta-hydroxylase activity of 3A12.
      Addition of the carboxyl terminal 44 3A12 residues to the 3A26 triple mutant
      doubled progesterone 6beta-hydroxylase activity. This is the first study to use
      catalytically distinct cytochromes P-450 3A from the same species in the
      elucidation of structure-function relationships.

PMID- 9927615
TI  - The alpha9 nicotinic acetylcholine receptor shares pharmacological properties
      with type A gamma-aminobutyric acid, glycine, and type 3 serotonin receptors.
AB  - In the present study, we provide evidence that the alpha9 nicotinic acetylcholine
      receptor (nAChR) shares pharmacological properties with members of the Cys-loop
      family of receptors. Thus, the type A gamma-aminobutyric acid receptor antagonist
      bicuculline, the glycinergic antagonist strychnine, and the type 3 serotonin
      receptor antagonist ICS-205,930 block ACh-evoked currents in alpha9-injected
      Xenopus laevis oocytes with the following rank order of potency: strychnine > ICS
      205,930 > bicuculline. Block by antagonists was reflected in an increase in the
      acetylcholine (ACh) EC50 value, with no changes in agonist maximal response or
      Hill coefficient, which suggests a competitive type of block. Moreover, whereas
      neither gamma-aminobutyric acid nor glycine modified ACh-evoked currents,
      serotonin blocked responses to ACh in a concentration-dependent manner. The
      present results suggest that the alpha9 nAChR must conserve in its primary
      structure some residues responsible for ligand binding common to other Cys-loop
      receptors. In addition, it adds further evidence that the alpha9 nAChR and the
      cholinergic receptor present at the base of cochlear outer hair cells have
      similar pharmacological properties.

PMID- 9927617
TI  - Replacement of threonine 394 by alanine facilitates internalization and
      resensitization of the rat mu opioid receptor.
AB  - Signaling of G protein-coupled receptors is terminated by phosphorylation of
      intracellular serine and threonine residues. Resensitization of these receptors
      requires internalization and subsequent dephosphorylation. We have recently shown
      that the resensitization rate of the rat micro opioid receptor (MOR) isoforms
      MOR1 and MOR1B is mainly determined by the amino acid composition of their
      alternatively spliced C-terminal tails. Upon agonist stimulation, MOR1B passes
      through an accelerated cycle of receptor endocytosis and reactivation, which in
      turn promotes a greater resistance to agonist-induced desensitization, as
      compared with MOR1. Given the fact that MOR1B lacks only one putative
      phosphorylation site (T394 of MOR1), we replaced this threonine by an alanine and
      stably expressed the wild-type MOR1 and its T394A mutant in mouse neuroblastoma
      Neuro2a cells. We show that during prolonged [D-Ala2, MePhe4, Gly5-ol]enkephalin
      exposure (5 h), the T394A receptor mutant desensitized at a slower rate than
      MOR1. In contrast, T394A is more rapidly removed from the cell surface than MOR1,
      as determined by flow cytometry using epitope-tagged receptors. This fast
      internalization was followed by immediate resensitization of T394A during 20 min
      of agonist removal while the wild-type MOR1 remained inactive. Similar to MOR1B,
      rapid internalization and reactivation of T394A may explain its delayed
      desensitization. These findings suggest that T394 represents a negative
      regulatory signal for MOR1 internalization. Furthermore, phosphorylation of this
      threonine residue may influence the time course of micro opioid receptor
      resensitization.

PMID- 9927616
TI  - Stimulation of the extracellular signal-regulated kinase 1/2 pathway by human
      beta-3 adrenergic receptor: new pharmacological profile and mechanism of
      activation.
AB  - We present evidence that stimulation of the human beta-3 adrenergic receptor
      (AR), expressed in Chinese hamster ovary/K1 cells, specifically activates the
      mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)1
      and 2, but not JNK or p38. The extent and kinetics of the ERK stimulation by the
      beta-3 AR are identical with those of the endogenic insulin receptor. However,
      insulin augments cellular proliferation, whereas beta-3 AR agonists inhibit
      proliferation due to the production of cyclic AMP. The pharmacological profile of
      the ERK activation by the beta-3 AR differs significantly from its activation of
      adenylyl cyclase. The order of potency and intrinsic activities of both natural
      ligands, norepinephrine and epinephrine, is inversed between both signaling
      pathways. In addition, BRL 37344 and propranolol, ligands that act as agonists in
      the stimulation of cyclase, act as antagonists for ERK activation. The activation
      of ERK1/2 is sensitive to pertussis toxin, suggesting that the beta-3 AR, in
      addition to its interaction with Gs, can couple to Gi/o. Furthermore, the
      activation of ERK by the beta-3 AR is sensitive to PD98059, wortmannin, and
      LY294002, indicating a crucial role for mitogen-activated protein kinase kinase
      and phosphatidylinositol-3 kinase (PI3K), respectively. A beta-3 AR-mediated
      stimulation of PI3K is confirmed by the observation that the selective agonist
      CGP 12177A specifically activates protein kinase B. As was observed for the
      activation of ERK, the activation of protein kinase B is inhibited by
      preincubation with pertussis toxin and PI3K inhibitors, suggesting that both are
      a consequence of a Gi/o-mediated activation of PI3K.

PMID- 9927618
TI  - The steroid promegestone is a noncompetitive antagonist of the Torpedo nicotinic
      acetylcholine receptor that interacts with the lipid-protein interface.
AB  - 17,21-Dimethyl-19-nor-pregn-4,9-diene-3,20-dione (promegestone) was used to
      characterize the mechanism of inhibition of nicotinic acetylcholine (ACh)
      receptors (AChR) by progestin steroids. Promegestone reversibly inhibited ACh
      induced currents of Torpedo AChRs expressed in Xenopus oocytes. Between 1-30
      microM promegestone produced a concentration-dependent enhancement of the
      equilibrium binding affinity of [3H]ACh to Torpedo AChR-rich membranes. For AChRs
      in the presence of agonist (desensitized state) promegestone was a more potent
      inhibitor of the binding of the noncompetitive antagonist [3H]phencyclidine (IC50
      = 9 microM) than of [3H]histrionicotoxin (IC50 approximately 100 microM). To
      identify AChR domains in contact with the steroid, AChR-rich membranes
      equilibrated with [3H]promegestone were irradiated at 312 nm, and 3H-labeled
      amino acids were identified by amino-terminal sequencing of fragments isolated
      from subunit proteolytic digests. Within AChR alpha-subunit, 70% of 3H was
      covalently incorporated in a 10-kDa fragment beginning at Asn-339 and containing
      the M4 membrane spanning segment, and 30% was in a 20-kDa fragment beginning at
      Ser-173 and containing the M1-M3 segments. Fragments containing the M2 channel
      domains as well as the M4 segments were isolated from proteolytic digests of AChR
      subunits and subjected to amino-terminal sequence analysis. No evidence of
      [3H]promegestone incorporation was detected in any of the M2 segments. The amino
      acids in the M4 segments labeled by [3H]promegestone were among those previously
      shown to be in contact with the lipid bilayer (). These results indicate that the
      steroid promegestone is an AChR noncompetitive antagonist that may alter AChR
      function by interactions at the lipid-protein interface.

PMID- 9927619
TI  - A novel positive regulatory element that enhances hamster CYP2A8 gene expression
      mediated by xenobiotic responsive element.
AB  - CYP2A8 is a major form of cytochrome P-450 inducible by 3-methylcholanthrene in
      Syrian hamster liver. To identify DNA elements necessary for the transcriptional
      activation of the CYP2A8 gene, we analyzed the regulatory region of the CYP2A8
      gene and conducted transient transfection experiments of CYP2A8-luciferase fusion
      plasmids in primary cultures of hamster hepatocytes. We analyzed up to -5 kb of
      the 5'-flanking region and found the region sufficient for the 3
      methylcholanthrene-inducible gene expression. This region contained a consensus
      sequence for xenobiotic responsive element (XRE) between -2366 and -2349, which
      was shown to be essential for induction of the gene expression. Furthermore, we
      found a novel positive regulatory element for XRE-mediated gene expression (PREX)
      located upstream of the XRE. This element is not identified in any genes
      inducible by 3-methylcholanthrene so far reported. Without PREX, the XRE-mediated
      promoter activity was enhanced nearly 10-fold, whereas with PREX, the activity
      was enhanced 20-fold over the basal level. Gel mobility shift assays revealed
      specific binding of nuclear proteins to PREX. Mutations and deletions of PREX
      caused a loss of the binding and promoter-enhancing activities, respectively.
      Moreover, transient expression experiments showed that the enhancing activity of
      PREX was not observed in Drosophila Schneider's line 2 cells, which were shown to
      lack the PREX binding proteins.

PMID- 9927620
TI  - Inhibition of cardiac L-type calcium channels by epoxyeicosatrienoic acids.
AB  - Epoxyeicosatrienoic acids (EETs), products of the cytochrome P-450 monooxygenase
      metabolism of arachidonic acid, can regulate the activity of ion channels. We
      examined the effects of EETs on cardiac L-type Ca2+ channels that play important
      roles in regulating cardiac contractility, controlling heart rate, and mediating
      slow conduction in normal nodal cells and ischemic myocardium. Our experimental
      approach was to reconstitute porcine L-type Ca2+ channels into planar lipid
      bilayers where we could control the aqueous and lipid environments of the
      channels and the regulatory pathways that change channel properties. We found
      that 20 to 125 nM EETs inhibited the open probability of reconstituted L-type
      Ca2+ channels, accelerated the inactivation of the channels, and reduced the
      unitary current amplitude of open channels. There was no selectivity among
      different EET regioisomers or stereoisomers. When 11,12-EET was esterified to the
      sn-2 position of phosphatidylcholine, restricting it to the hydrophobic phase of
      the planar lipid bilayer, the reconstituted channels were similarly inhibited,
      suggesting that the EET interacts directly with Ca2+ channels through the lipid
      phase. The inhibitory effects of EET persisted in the presence of microcystin, an
      inhibitor of protein phosphatases 1 and 2A, suggesting that dephosphorylation was
      not the mechanism through which these eicosanoids down-regulate channel activity.
      This inhibition may be an important protective mechanism in the setting of
      cardiac ischemia where arachidonic acid levels are dramatically increased and
      EETs have been shown to manifest preconditioning-like effects.

PMID- 9927621
TI  - No role for Ca++ or protein kinase C in alpha-1A adrenergic receptor activation
      of mitogen-activated protein kinase pathways in transfected PC12 cells.
AB  - We studied the role of Ca++ and protein kinase C (PKC) in alpha-1A adrenergic
      receptor (AR)-mediated activation of mitogen-activated protein kinase pathways in
      PC12 cells. In PC12 cells stably transfected with the human alpha-1A AR,
      norepinephrine (NE) strongly activated both extracellular signal regulated
      kinases (ERKs) and c-jun-NH2-terminal kinases (JNK). Ten nanomolar thapsigargin
      (TG) increased cytoplasmic Ca++ at least as much as NE but did not activate ERKs
      or JNK. Higher concentrations of TG caused a small activation of ERKs but not
      JNK. Emptying [Ca++]i stores by pretreatment with TG prevented the NE-stimulated
      increase in [Ca++]i but not ERK or JNK activation. The Ca++ chelator bis(2
      aminophenoxy)ethane-N-N-N'-N'-tetraacetate (BAPTA) dose dependently abolished NE
      stimulated Ca++ responses but not ERK or JNK activation. NE increased tyrosine
      phosphorylation of Pyk2, and this response was neither blocked by BAPTA nor
      mimicked by TG. The phorbol ester tumor promoting agent (TPA) caused a dose
      dependent activation of ERKs that was potentiated by 10 nM TG. TPA caused only a
      small activation of JNK relative to that caused by NE, which was not affected by
      TG. The potent PKC inhibitor bisindolylmaleimide I dose dependently inhibited ERK
      and JNK activation by TPA, but not NE. ATP and UTP activated similar mitogen
      activated protein kinase responses through endogenous P2Y2 receptors, and these
      responses were not blocked by BAPTA or bisindolylmaleimide I, suggesting that
      these results may be generalizable to other Gq/11-coupled receptors. The results
      suggest that Ca++ release and PKC activation are neither necessary nor sufficient
      for alpha-1A AR-mediated activation of mitogenic responses in PC12 cells.

PMID- 9927622
TI  - Inhibition of astroglial nitric oxide synthase type 2 expression by idazoxan.
AB  - Binding of idazoxan (IDA) to imidazoline receptors of the I2 subtype in
      astrocytes influences astroglial gene expression as evidenced by increased
      expression of glial fibrillary acidic protein and mRNA. To determine whether IDA
      affected glial inflammatory gene expression, we tested the effects of IDA on
      astroglial nitric oxide synthase type-2 (NOS-2) expression. NOS-2 was induced in
      primary rat astrocytes and C6 glioma cells by incubation with 1 microgram/ml
      lipopolysaccharide (LPS) plus three cytokines (tumor necrosis factor-alpha,
      interleukin-1beta, and interferon-gamma) or three cytokines alone. Cells were
      incubated with 1-100 microM IDA, and at 24 h NOS-2 expression assessed. In
      astrocytes and C6 cells, preincubation with IDA dose-dependently inhibited
      nitrite accumulation (IC50 approximately 25 microM), accompanied by a reduction
      in NOS-2 protein levels and L-citrulline synthesis activity in cell lysates. IDA
      also inhibited nitrite production in LPS stimulated RAW 264.7 macrophages. In
      astrocytes, but not C6 cells, longer preincubation times with IDA yielded
      significantly greater suppression, and maximal suppression (>90%) was achieved
      after a 8 h preincubation in 100 microM IDA. The degree of inhibition was
      diminished whether IDA was added after LPS plus cytokine mixture. In contrast to
      NE, continuous incubation with IDA was required to achieve suppression. IDA
      reduced induction of NOS-2 protein levels, steady state NOS-2 mRNA levels, and
      activity of a NOS-2 promoter construct stably transfected in C6 cells. These
      results show that IDA inhibits NOS-2 activity and protein expression in glial
      cells and macrophages, and suggest that this occurs by decreasing transcription
      from the NOS-2 promoter.

PMID- 9927623
TI  - Dexamethasone stimulates human A1 adenosine receptor (A1AR) gene expression
      through multiple regulatory sites in promoter B.
AB  - The expression of the human A1 adenosine receptor gene is controlled by two
      promoters, promoters A and B, and they are located 600 base pairs apart. The
      characteristics of the two promoters differ by the activity of expression, tissue
      specificity, and the potential regulatory elements around them. Promoter A is
      more active but its expression is observed only in selected tissues, whereas
      promoter B is constitutively expressed but at much reduced levels. In Chinese
      hamster ovary (CHO) cells transiently transfected with plasmids containing either
      promoter linked to a reporter gene, dexamethasone (dex) can stimulate (or
      enhance) the expression of promoter B much more effectively than that of promoter
      A. Mutation and deletion studies on plasmids containing promoter B have shown
      that the stimulation is mediated through multiple regulatory sites, including a
      serum response element, AP1, and TATA box. However, a single-glucocorticoid
      response element monomer-binding site between promoters A and B does not have
      significant contribution to dex-regulated expression. The interactions between
      glucocorticoid receptor (GR) and some regulatory sites are probably occurring via
      this protein (GR) interacting with other DNA-binding proteins because there is no
      GR DNA-binding sequence in the sites studied. The stimulation can be eliminated
      by mifepristone, an antagonist of GR, indicating the involvement of GR in gene
      regulation. In addition, dex treatment also stimulated the expression of A1
      adenosine receptors in CHO cells transfected with the plasmids containing
      contiguous genomic sequences of promoter B or promoters A and B linked to the
      receptor-coding sequence. When promoter A is active and both promoter A and B are
      present in a construct, dex treatment induced a much smaller percentage of
      stimulation.

PMID- 9927624
TI  - Inhibition of glucocorticoid receptor binding by nitric oxide.
AB  - Septic shock is a dangerous condition with high mortality rates. In sepsis, the
      inducible form of nitric oxide (NO) synthase is induced, releasing high amounts
      of NO. Glucocorticoids have potent anti-inflammatory properties and are very
      effective in inhibiting the induction of this enzyme if administered before the
      shock onset. It is known that glucocorticoid receptor (GR) has critical cysteine
      residues for steroid binding in its hormone-binding and DNA-binding domains. It
      has also been reported that NO reacts with ---SH groups, forming S-nitrosothiols.
      Therefore, we examined the potential effect of NO on the ligand-binding ability
      of GR. NO donors (S-nitroso-acetyl-DL-penicillamine, S-nitroso-DL-penicillamine,
      or S-nitroso-glutathione) decreased, in a time- and dose-dependent manner, the
      binding of [3H]triamcinolone to immunoprecipitated GR from mouse L929
      fibroblasts. The nonnitrosylated parent molecules, N-acetyl-DL-penicillamine, and
      reduced gluthatione were without effect. Scatchard plots revealed that the number
      of ligand binding sites and Kd were reduced (50%) by NO donors. Western blot
      analysis ruled out the possibility that dissociation of GR/heat shock protein 90
      heterocomplex or decrease in GR protein would account for the inhibitory effect
      of NO. Decreased ligand binding to GR was found when NO donors were incubated
      with intact fibroblasts. Incubation with NO donors also decreased the steroid
      induced reduction in [3H]uridine incorporation into RNA. All of these NO effects
      were inhibited by the thiol-protecting agent dithiothreitol. Therefore, S
      nitrosylation of critical ---SH groups in GR by NO with consequent decreases in
      binding and affinity may be the mechanisms which explain the failure of
      glucocorticoids to exert their anti-inflammatory effects in septic shock.

PMID- 9927625
TI  - Distinct mechanisms for activation of the opioid receptor-like 1 and kappa-opioid
      receptors by nociceptin and dynorphin A.
AB  - To understand how two structurally analogous ligand-receptor systems, the
      nociceptin/opioid receptor-like 1 (ORL1) and dynorphin A/kappa-opioid receptor 1
      (KOR1) systems, achieve selectivity, receptor chimeras were generated and
      analyzed. Replacing discrete domains located between the N-terminus and top of
      the third transmembrane helix of the KOR1 by the homologous domains of the ORL1
      receptor yields hybrid receptors, which, in comparison with the parent KOR1,
      display up to 300-fold increased affinity but low sensitivity toward nociceptin,
      and unaltered (high) affinity and sensitivity toward dynorphin A. These
      substitutions contribute elements for binding of nociceptin but do not suppress
      determinants necessary for binding and potency of dynorphin A. More importantly,
      further replacement in these chimeras of the second extracellular loop with that
      of the ORL1 receptor fully restores responsiveness to nociceptin without
      impairing responsiveness to dynorphin A. A bifunctional hybrid receptor has thus
      been identified that binds and responds to both nociceptin and dynorphin A as
      efficiently as the ORL1 receptor does to nociceptin and the KOR1 to dynorphin A.
      Together, these results suggest that distinct peptide activation mechanisms
      operate in the two receptor systems. In particular, the second extracellular
      receptor loop appears to be an absolute requirement for activation of the ORL1
      receptor by nociceptin, but not for activation of the KOR1 by dynorphin A.

PMID- 9927626
TI  - Three distinct D-amino acid substitutions confer potent antiangiogenic activity
      on an inactive peptide derived from a thrombospondin-1 type 1 repeat.
AB  - Mal II, a 19-residue peptide derived from the second type 1 properdin-like repeat
      of the antiangiogenic protein thrombospondin-1 (TSP-1), was inactive in
      angiogenesis assays. Yet the substitution of any one of three L-amino acids by
      their D-enantiomers conferred on this peptide a potent antiangiogenic activity
      approaching that of the intact 450-kDa TSP-1. Substituted peptides inhibited the
      migration of capillary endothelial cells with an ED50 of 8.5 nM for the D-Ile-15
      substitution, 10 nM for the D-Ser-4 substitution, and 0.75 nM for the D-Ser-5
      substitution. A peptide with D-Ile at position 15 could be shortened to its last
      seven amino acids with little loss in activity. Like whole TSP-1, the Mal II D
      Ile derivative inhibited a broad range of angiogenic inducers, was selective for
      endothelial cells, and required CD36 receptor binding for activity. A variety of
      end modifications further improved peptide potency. An ethylamide-capped
      heptapeptide was also active systemically in that when injected i.p. it rendered
      mice unable to mount a corneal angiogenic response, suggesting the potential
      usefulness of such peptides as antiangiogenic therapeutics.

PMID- 9927627
TI  - Constitutively active alpha-1b adrenergic receptor mutants display different
      phosphorylation and internalization features.
AB  - We compared the phosphorylation and internalization properties of constitutively
      active alpha-1b adrenergic receptor (AR) mutants carrying mutations in two
      distant receptor domains, i.e., at A293 in the distal part of the third
      intracellular loop and at D142 of the DRY motif lying at the end of the third
      transmembrane domain. For the A293E and A293I mutants the levels of agonist
      independent phosphorylation were 150% and 50% higher than those of the wild-type
      alpha-1b AR, respectively. On the other hand, for the constitutively active D142A
      and D142T mutants, the basal levels of phosphorylation were similar to those of
      the wild-type alpha-1b AR and did not appear to be further stimulated by
      epinephrine. Overexpression of the guanyl nucleotide binding regulatory protein
      coupled receptor kinase GRK2 further increases the basal phosphorylation of the
      A293E mutant, but not that of D142A mutant. Both the wild-type alpha-1b AR and
      the A293E mutant could undergo beta-arrestin-mediated internalization. The
      epinephrine-induced internalization of the constitutively active A293E mutant was
      significantly higher than that of the wild-type alpha-1b AR. In contrast, the
      D142A mutant was impaired in its ability to interact with beta-arrestin and to
      undergo agonist-induced internalization. Interestingly, a double mutant
      A293E/D142A retained very high constitutive activity and regulatory properties of
      both the A293E and D142A receptors. These findings demonstrate that two
      constitutively activating mutations occurring in distant receptor domains of the
      alpha-1b AR have divergent effects on the regulatory properties of the receptor.

PMID- 9927628
TI  - A structure-based approach to nicotinic receptor pharmacology.
AB  - Infrared difference spectroscopy has been used to examine the structural effects
      of local anesthetic (LA) binding to the nicotinic acetylcholine receptor (nAChR).
      Several LAs induce subtle changes in the vibrational spectrum of the nAChR over a
      range of concentrations consistent with their reported nAChR-binding affinities.
      At concentrations of the desensitizing LAs prilocaine and lidocaine consistent
      with their binding to the ion channel pore, the vibrational changes suggest the
      stabilization of an intermediate conformation that shares structural features in
      common with both the resting and desensitized states. Higher concentrations of
      prilocaine and lidocaine, as well as the LA dibucaine, lead to additional binding
      to the neurotransmitter-binding site, the formation of physical interactions
      (most notably cation-tyrosine interactions) between LAs and neurotransmitter
      binding-site residues, and the subsequent formation of a presumed desensitized
      nAChR. Although concentrations of the LA tetracaine consistent with binding to
      the ion channel pore elicit a reversed pattern of spectral changes suggestive of
      a resting state-like nAChR, higher concentrations also lead to neurotransmitter
      site binding and desensitization. Our results suggest that LAs stabilize multiple
      conformations of the nAChR by binding to at least two conformationally sensitive
      LA-binding sites. The spectra also reveal subtle differences in the strengths of
      the physical interactions that occur between LAs and binding-site residues. These
      differences correlate with LA potency at the nAChR.

PMID- 9927629
TI  - Isolation of cDNAs encoding cellular drug-binding proteins using a novel
      expression cloning procedure: drug-western.
AB  - A rapid and convenient new method for isolating the genes encoding cellular drug
      binding proteins is described. This method, drug-western, is based on the use of
      the drug conjugated with a marker molecule as a probe for the screening of a cDNA
      library. Unlike the other methods, this method allows us to identify the genes
      for trace amounts of cellular drug-binding proteins without purification. We have
      used this approach to isolate human cDNA clones encoding binding proteins of HMN
      154 ((E)-4-[2-[2-(p-methoxy-benzene-sulfonamide) phenyl]ethenyl] pyridine), a
      novel benzenesulfonamide anticancer compound (Katoh and Hidaka 1997). The
      proteins encoded by two of the isolated clones are identical to NF-YB, B subunit
      of nuclear transcription factor NF-Y, and thymosin beta-10, respectively.
      Recombinants of both proteins bind specifically to HMN-154 in vitro. Comparison
      of amino acid sequences between these proteins shows the sequence similarity in a
      short amino acid stretch [K(X)AKXXK]. Deletion or mutation of this region causes
      the significant loss of binding of both proteins to HMN-154. Furthermore, HMN-154
      inhibits DNA binding of NF-Y to the human major histocompatibility complex class
      II human leukocyte antigen DRA Y-box sequence in a dose-dependent manner.
      Interestingly, other binding proteins identified by this method also possess the
      same or a similar motif. These results clearly demonstrate that NF-YB and
      thymosin beta-10 are specific cellular binding proteins of HMN-154 and that this
      shared region is necessary for the binding to HMN-154. Hence, this new method is
      thought to be useful for the identification of drug-binding proteins.

PMID- 9927630
TI  - Purine and pyrimidine nucleotides inhibit a noninactivating K+ current and
      depolarize adrenal cortical cells through a G protein-coupled receptor.
AB  - Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K+ current
      (IAC) that sets the resting membrane potential and may mediate depolarization
      dependent cortisol secretion. External ATP stimulates cortisol secretion through
      activation of a nucleotide receptor. In whole-cell patch clamp recordings from
      bovine AZF cells, we found that ATP selectively inhibited IAC K+ current by a
      maximum of 75.7 +/- 3% (n = 13) with a 50% inhibitory concentration of 1.3
      microM. A rapidly inactivating A-type K+ current was not inhibited by ATP. Other
      nucleotides, including ADP and the pyrimidines UTP and UDP, also inhibited IAC,
      whereas 2-methylthio-ATP (2-MeSATP) and CTP were completely ineffective. The rank
      order of potency for six nucleotides was UTP = ADP > ATP > UDP >> 2-MeSATP = CTP.
      At maximally effective concentrations, UTP, ADP, and UDP inhibited IAC current by
      81.4 +/- 5.2% (n = 7), 70.7 +/- 7.2% (n = 4), and 65.2 +/- 7.9% (n = 5),
      respectively. Inhibition of IAC by external ATP was reduced from 71. 3 +/- 3.2%
      to 22.8 +/- 4.5% (n = 18) by substituting guanosine 5'-O-2-(thio) diphosphate for
      GTP in the patch pipette. Inhibition of IAC by external ATP (10 microM) was
      markedly suppressed (to 17.3 +/- 5.5%, n = 9) by the nonspecific protein kinase
      antagonist staurosporine (1 microM) and eliminated by substituting the
      nonhydrolyzable ATP analog 5-adenylyl-imidodiphosphate or UTP for ATP in the
      pipette. ATP-mediated inhibition of IAC was not altered by the kinase C
      antagonist calphostin C, the calmodulin inhibitory peptide, or by buffering the
      intracellular (pipette) Ca++ with 20 mM 1,2-bis-(2-aminophenoxy)ethane-N, N,N',N'
      tetraacetic acid. In current clamp recordings, ATP and UTP (but not CTP)
      depolarized AZF cells at concentrations that inhibited IAC K+ current. These
      results demonstrate that bovine AZF cells express a nucleotide receptor with a
      P2Y3 agonist profile that is coupled to the inhibition of IAC K+ channels through
      a GTP-binding protein. The inhibition of IAC K+ current and associated membrane
      depolarization are the first cellular responses demonstrated to be mediated
      through this receptor. Nucleotide inhibition of IAC proceeds through a pathway
      that is independent of phospholipase C, but that requires ATP hydrolysis. The
      identification of a new signaling pathway in AZF cells, whereby activation of a
      nucleotide receptor is coupled to membrane depolarization through inhibition of a
      specific K+ channel, suggests a mechanism for ATP-stimulated corticosteroid
      secretion that depends on depolarization-dependent Ca++ entry. This may be a
      means of synchronizing the stress-induced secretion of corticosteroids and
      catecholamines from the adrenal gland.

PMID- 9927631
TI  - Enhanced binding to DNA and topoisomerase I inhibition by an analog of the
      antitumor antibiotic rebeccamycin containing an amino sugar residue.
AB  - Many antitumor agents contain a carbohydrate side chain appended to a DNA
      intercalating chromophore. This is the case with anthracyclines such as
      daunomycin and also with indolocarbazoles including the antibiotic rebeccamycin
      and its tumor active analog, NB506. In each case, the glycoside residue plays a
      significant role in the interaction of the drug with the DNA double helix. In
      this study we show that the DNA-binding affinity and sequence selectivity of a
      rebeccamycin derivative can be enhanced by replacing the glucose residue with a
      2'-aminoglucose moiety. The drug-DNA interactions were studied by thermal
      denaturation, fluorescence, and footprinting experiments. The thermodynamic
      parameters indicate that the newly introduced amino group on the glycoside
      residue significantly enhanced binding to DNA by increasing the contribution of
      the polyelectrolyte effect to the binding free energy, but does not appear to
      participate in any specific molecular contacts. The energetic contribution of the
      amino group of the rebeccamycin analog was found to be weaker than that of the
      sugar amino group of daunomycin, possibly because the indolocarbazole derivative
      is only partially charged at neutral pH. Topoisomerase I-mediated DNA cleavage
      studies reveal that the OH-->NH2 substitution does not affect the capacity of the
      drug to stabilize enzyme-DNA covalent complexes. Cytotoxicity studies with P388
      leukemia cells sensitive or resistant to camptothecin suggest that topoisomerase
      I represents a privileged intracellular target for the studied compounds. The
      role of the sugar amino group is discussed. The study provides useful guidelines
      for the development of a new generation of indolocarbazole-based antitumor
      agents.

PMID- 9927632
TI  - The startle disease mutation Q266H, in the second transmembrane domain of the
      human glycine receptor, impairs channel gating.
AB  - Hyperekplexia (startle disease) results from mutations in the glycine receptor
      chloride channel that disrupt inhibitory synaptic transmission. The Q266H
      missense mutation is the only hyperekplexia mutation located in the transmembrane
      domains of the receptor. Using recombinant expression and patch-clamping
      techniques, we have investigated the functional properties of this mutation. The
      ability of glycine and taurine to open the channel was reduced in the mutated
      channel, as shown by a 6-fold shift in the concentration-response curve for both
      agonists. This was not accompanied by similar changes in agonist displacement of
      strychnine binding, suggesting that the mutation affects functions subsequent to
      ligand binding. Taurine was also converted to a weak partial agonist and
      antagonized the actions of glycine, consistent with changes in its channel gating
      efficacy. Because the Q266H mutation is within the pore-forming second
      transmembrane domain, we tested for a direct interaction with permeating ions. No
      change in either the cation/anion selectivity ratio or in single channel
      conductance levels was observed. No differential effects of Zn++, pH, and
      diethylpyrocarbonate were observed, implying that the histidine side chain is not
      exposed to the channel lumen. Single-channel recordings revealed a significant
      reduction in open times in the mutant receptors, at both high and low agonist
      concentrations, consistent with the open state of the channel being less stable.
      This study demonstrates that residues within the second transmembrane domain of
      ligand-gated ion channel receptors, even those whose side chains do not directly
      interact with permeating ions, can affect the kinetics of channel gating.

PMID- 9927633
TI  - Induction of p53-dependent, insulin-like growth factor-binding protein-3-mediated
      apoptosis in glioblastoma multiforme cells by a protein kinase Calpha antisense
      oligonucleotide.
AB  - Protein kinase Calpha (PKCalpha) expression is related to tumor progression in
      glioblastoma multiforme (GBM), the most common malignant brain tumor in adults.
      To determine whether PKCalpha regulates an anti-apoptotic survival pathway in
      GBM, A172 GBM cells were treated with a PKCalpha-selective antisense
      oligonucleotide. PKCalpha antisense oligonucleotide treatment was accompanied by
      reduction in PKCalpha levels and the induction of wild-type p53 and insulin-like
      growth factor-binding protein-3 (IGFBP3) 24-72 h after treatment, a period that
      coincided with the appearance of apoptotic cell death as detected by DNA
      fragmentation. There were no significant changes in the levels of Bcl-XL, Bax,
      and p21(WAF1). Induction of p53 after PKCalpha down-regulation was not associated
      with increased mRNA expression, but increased IGFBP3 levels were accompanied by
      increased mRNA levels. Recombinant human IGFBP3 induced an apoptotic effect that
      was similar to the PKCalpha antisense oligonucleotide, and its effect was blocked
      by IGF-I. These results suggest that one mechanism by which PKCalpha produces its
      antiapoptotic activity in GBM cells is by suppressing the p53-mediated activation
      of IGFBP3.

PMID- 9927634
TI  - Of abscission and other breakthroughs.

PMID- 9927635
TI  - Phenotype of the tomato high pigment-2 mutant is caused by a mutation in the
      tomato homolog of DEETIOLATED1.
AB  - Tomato high pigment (hp) mutants are characterized by their exaggerated
      photoresponsiveness. Light-grown hp mutants display elevated levels of
      anthocyanins, are shorter and darker than wild-type plants, and have dark green
      immature fruits due to the overproduction of chlorophyll pigments. It has been
      proposed that HP genes encode negative regulators of phytochrome signal
      transduction. We have cloned the HP-2 gene and found that it encodes the tomato
      homolog of the nuclear protein DEETIOLATED1 (DET1) from Arabidopsis. Mutations in
      DET1 are known to result in constitutive deetiolation in darkness. In contrast to
      det1 mutants, tomato hp-2 mutants do not display any visible phenotypes in the
      dark but only very weak phenotypes, such as partial chloroplast development.
      Furthermore, whereas det1 mutations are epistatic to mutations in phytochrome
      genes, analysis of similar double mutants in tomato showed that manifestation of
      the phenotype of the hp-2 mutant is strictly dependent upon the presence of
      active phytochrome. Because only one DET1 gene is likely to be present in each of
      the two species, our data suggest that the phytochrome signaling pathways in
      which the corresponding proteins function are regulated differently in
      Arabidopsis and tomato.

PMID- 9927636
TI  - Interactions between jointless and wild-type tomato tissues during development of
      the pedicel abscission zone and the inflorescence meristem.
AB  - The jointless mutation of tomato results in the formation of flower pedicels that
      lack an abscission zone and inflorescence meristems that revert to vegetative
      growth. We have analyzed periclinal chimeras and mericlinal sectors of jointless
      and wild-type tissue to determine how cells in different meristem layers (L1, L2,
      and L3) and their derivatives interact during these two developmental processes.
      Cells in the inner meristem layer, L3, alone determined whether the meristem
      maintained the inflorescence state or reverted to vegetative growth. Moreover, L3
      derivatives determined whether a functional pedicel abscission zone formed.
      Limited and disorganized autonomous development of wild-type L2-derived cells
      occurred when they overlay mutant tissue. Adjacent mutant and wild-type L3
      derived tissues in pedicels developed autonomously, indicating little or no
      lateral communication. Only the outermost L3-derived cells within the pedicel
      were capable of orchestrating normal pedicel development in overlying tissues,
      revealing the special status of those cells as coordinators of development for L1
      and L2-derived cells, whereas the innermost L3-derived cells developed
      autonomously but did not influence the development of other cells.

PMID- 9927637
TI  - Antisense repression of vacuolar and cell wall invertase in transgenic carrot
      alters early plant development and sucrose partitioning.
AB  - To unravel the functions of cell wall and vacuolar invertases in carrot, we used
      an antisense technique to generate transgenic carrot plants with reduced enzyme
      activity. Phenotypic alterations appeared at very early stages of development;
      indeed, the morphology of cotyledon-stage embryos was markedly changed. At the
      stage at which control plantlets had two to three leaves and one primary root,
      shoots of transgenic plantlets did not separate into individual leaves but
      consisted of stunted, interconnected green structures. When transgenic plantlets
      were grown on media containing a mixture of sucrose, glucose, and fructose rather
      than sucrose alone, the malformation was alleviated, and plantlets looked normal.
      Plantlets from hexose-containing media produced mature plants when transferred to
      soil. Plants expressing antisense mRNA for cell wall invertase had a bushy
      appearance due to the development of extra leaves, which accumulated elevated
      levels of sucrose and starch. Simultaneously, tap root development was markedly
      reduced, and the resulting smaller organs contained lower levels of
      carbohydrates. Compared with control plants, the dry weight leaf-to-root ratio of
      cell wall invertase antisense plants was shifted from 1:3 to 17:1. Plants
      expressing antisense mRNA for vacuolar invertase also had more leaves than did
      control plants, but tap roots developed normally, although they were smaller, and
      the leaf-to-root ratio was 1.5:1. Again, the carbohydrate content of leaves was
      elevated, and that of roots was reduced. Our data suggest that acid invertases
      play an important role in early plant development, most likely via control of
      sugar composition and metabolic fluxes. Later in plant development, both
      isoenzymes seem to have important functions in sucrose partitioning.

PMID- 9927638
TI  - The Arabidopsis ssi1 mutation restores pathogenesis-related gene expression in
      npr1 plants and renders defensin gene expression salicylic acid dependent.
AB  - The Arabidopsis NPR1 gene was previously shown to be required for the salicylic
      acid (SA)- and benzothiadiazole (BTH)-induced expression of pathogenesis-related
      (PR) genes and systemic acquired resistance. The dominant ssi1 (for suppressor of
      SA insensitivity) mutation characterized in this study defines a new component of
      the SA signal transduction pathway that bypasses the requirement of NPR1 for
      expression of the PR genes and disease resistance. The ssi1 mutation caused PR
      (PR-1, BGL2 [PR-2], and PR-5) genes to be constitutively expressed and restored
      resistance to an avirulent strain of Pseudomonas syringae pv tomato in npr1-5
      (previously called sai1) mutant plants. In addition, ssi1 plants were small,
      spontaneously developed hypersensitive response-like lesions, accumulated
      elevated levels of SA, and constitutively expressed the antimicrobial defensin
      gene PDF1.2. The phenotypes of the ssi1 mutant are SA dependent. When SA
      accumulation was prevented in ssi1 npr1-5 plants by expressing the SA-degrading
      salicylate hydroxylase (nahG) gene, all of the phenotypes associated with the
      ssi1 mutation were suppressed. However, lesion formation and expression of the PR
      genes were restored in these plants by the application of BTH. Interestingly,
      expression of PDF1.2, which previously has been shown to be SA independent but
      jasmonic acid and ethylene dependent, was also suppressed in ssi1 npr1-5 plants
      by the nahG gene. Furthermore, exogenous application of BTH restored PDF1.2
      expression in these plants. Our results suggest that SSI1 may function as a
      switch modulating cross-talk between the SA- and jasmonic acid/ethylene-mediated
      defense signal transduction pathways.

PMID- 9927639
TI  - The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5
      desaturation step leading to brassinosteroid biosynthesis.
AB  - Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf
      phenotypes in plants. Understanding the regulation of BR biosynthesis demands
      continued isolation and characterization of mutants corresponding to the genes
      involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic
      locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and
      analysis of endogenous levels of BR and sterol biosynthetic intermediates
      indicate that the defective step in dwf7-1 resides before the production of 24
      methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results
      from feeding studies with 13C-labeled mevalonic acid and compactin show that the
      defective step is specifically the Delta7 sterol C-5 desaturation, suggesting
      that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing
      of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first
      (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due
      to a shortage of substrate sterols and is the direct cause of the dwarf phenotype
      in dwf7.

PMID- 9927640
TI  - Pathogen-induced elicitin production in transgenic tobacco generates a
      hypersensitive response and nonspecific disease resistance.
AB  - The rapid and effective activation of disease resistance responses is essential
      for plant defense against pathogen attack. These responses are initiated when
      pathogen-derived molecules (elicitors) are recognized by the host. We have
      developed a strategy for creating novel disease resistance traits whereby
      transgenic plants respond to infection by a virulent pathogen with the production
      of an elicitor. To this end, we generated transgenic tobacco plants harboring a
      fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a
      Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under
      noninduced conditions, the transgene was silent, and no cryptogein could be
      detected in the transgenic plants. In contrast, infection by the virulent fungus
      P. parasitica var nicotianae stimulated cryptogein production that coincided with
      the fast induction of several defense genes at and around the infection sites.
      Induced elicitor production resulted in a localized necrosis that resembled a P.
      cryptogea-induced hypersensitive response and that restricted further growth of
      the pathogen. The transgenic plants displayed enhanced resistance to fungal
      pathogens that were unrelated to Phytophthora species, such as Thielaviopsis
      basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum
      disease resistance of a plant can be generated without the constitutive synthesis
      of a transgene product.

PMID- 9927641
TI  - Victorin induction of an apoptotic/senescence-like response in oats.
AB  - Victorin is a host-selective toxin produced by Cochliobolus victoriae, the causal
      agent of victoria blight of oats. Previously, victorin was shown to be bound
      specifically by two proteins of the mitochondrial glycine decarboxylase complex,
      at least one of which binds victorin only in toxin-sensitive genotypes in vivo.
      This enzyme complex is involved in the photorespiratory cycle and is inhibited by
      victorin, with an effective concentration for 50% inhibition of 81 pM. The
      photorespiratory cycle begins with ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco), and victorin was found to induce a specific
      proteolytic cleavage of the Rubisco large subunit (LSU). Leaf slices incubated
      with victorin for 4 hr in the dark accumulated a form of the LSU that is cleaved
      after the 14th amino acid. This proteolytic cleavage was prevented by the
      protease inhibitors E-64 and calpeptin. Another primary symptom of victorin
      treatment is chlorophyll loss, which along with the specific LSU cleavage is
      suggestive of a victorin-induced, senescence-like response. DNA from victorin
      treated leaf slices showed a pronounced laddering effect, which is typical of
      apoptosis. Calcium appeared to play a role in mediating the plant response to
      victorin because LaCl3 gave near-complete protection against victorin, preventing
      both leaf symptoms and LSU cleavage. The ethylene inhibitors aminooxyacetic acid
      and silver thiosulfate also gave significant protection against victorin-induced
      leaf symptoms and prevented LSU cleavage. The symptoms resulting from victorin
      treatment suggest that victorin causes premature senescence of leaves.

PMID- 9927642
TI  - Pollen-stigma adhesion in Brassica spp involves SLG and SLR1 glycoproteins.
AB  - The adhesion of pollen grains to the stigma is the first step of pollination in
      flowering plants. During this step, stigmas discriminate between pollen grains
      that can and cannot be permitted to effect fertilization. This selection is
      operated by various constituents of the cell walls of both partners. Several
      genes structurally related to the self-incompatibility system that prevents self
      pollination in Brassica spp are known to target their products into the stigma
      cell wall. We proposed previously that one of these genes, the one encoding the S
      locus glycoprotein (SLG)-like receptor 1 (SLR1), which is coexpressed with that
      encoding SLG, may participate in pollen-stigma adhesion. Here, we exploit a
      biomechanical assay to measure the pollen adhesion force and show that it is
      reduced both by transgenic suppression of SLR1 expression and by pretreatment of
      wild-type stigmas with anti-SLR1 antibodies, anti-SLG antibodies, or pollen coat
      protein extracts. Our results indicate a common adhesive function for the SLR1
      and SLG proteins in the pollination process.

PMID- 9927643
TI  - Modulation of plasma membrane H+-ATPase activity differentially activates wound
      and pathogen defense responses in tomato plants.
AB  - Systemin is an important mediator of wound-induced defense gene activation in
      tomato plants, and it elicits a rapid alkalinization of the growth medium of
      cultured Lycopersicon peruvianum cells. A possible mechanistic link between
      proton fluxes across the plasma membrane and the induction of defense genes was
      investigated by modulating plasma membrane H+-ATPase activity. Inhibitors of H+
      ATPase (erythrosin B, diethyl stilbestrol, and vanadate) were found to alkalinize
      the growth medium of L. peruvianum cell cultures and to induce wound response
      genes in whole tomato plants. Conversely, an activator of the H+-ATPase
      (fusicoccin) acidified the growth medium of L. peruvianum cell cultures and
      suppressed systemin-induced medium alkalinization. Likewise, in fusicoccin
      treated tomato plants, the wound- and systemin-triggered accumulation of wound
      responsive mRNAs was found to be suppressed. However, fusicoccin treatment of
      tomato plants led to the accumulation of salicylic acid and the expression of
      pathogenesis-related genes. Apparently, the wound and pathogen defense signaling
      pathways are differentially regulated by changes in the proton electrochemical
      gradient across the plasma membrane. In addition, alkalinization of the L.
      peruvianum cell culture medium was found to depend on the influx of Ca2+ and the
      activity of a protein kinase. Reversible protein phosphorylation was also shown
      to be involved in the induction of wound response genes. The plasma membrane H+
      ATPase as a possible target of a Ca2+-activated protein kinase and its role in
      defense signaling are discussed.

PMID- 9927644
TI  - Rapid Avr9- and Cf-9 -dependent activation of MAP kinases in tobacco cell
      cultures and leaves: convergence of resistance gene, elicitor, wound, and
      salicylate responses.
AB  - The Cf-9 resistance (R) gene from tomato confers resistance to the fungal
      pathogen Cladosporium fulvum expressing the corresponding, pathogen-derived
      avirulence gene product Avr9. To understand how an initial R/Avr recognition
      event is transmitted and triggers the induction of plant defenses, we
      investigated early Avr9/Cf-9-dependent activation of protein kinases in
      transgenic tobacco expressing the Cf-9 gene. We identified two protein kinases of
      46 and 48 kD, using myelin basic protein as substrate, that became rapidly
      activated in a strictly gene-for-gene manner within 2 to 5 min after Avr9
      elicitation in both Cf9 tobacco plants and derived cell cultures. Studies with
      pharmacological inhibitors and effectors revealed that Ca2+ influx and a
      phosphorylation event(s) are required for kinase activation, but neither enzyme
      is involved in the Avr9-dependent synthesis of active oxygen species. The
      activation of both kinases is achieved via post-translational mechanisms, and the
      activation but not inactivation step includes tyrosine phosphorylation. Using
      specific antibodies, we found that the 46- and 48-kD kinases were similiar to
      WIPK (for wound-induced protein kinase) and SIPK (for salicylic acid-induced
      protein kinase), two previously characterized mitogen-activated protein (MAP)
      kinases from tobacco. In addition, Cf9 tobacco plants and cell cultures showed an
      Avr9-dependent accumulation of the WIPK transcript. Cf9 tobacco suspension
      cultures are thus a unique system in which to analyze the earliest events in R
      gene function. These data indicate that (1) the R/Avr-mediated induction of plant
      defense is accomplished via several parallel signaling mechanisms, and (2) R/Avr
      dependent signal transduction pathways are interlinked at MAP kinases with
      responses of plants not only to non-race-specific elicitors but also to abiotic
      stimuli, such as wounding and mechanical stress.

PMID- 9927645
TI  - Jasmonate-based wound signal transduction requires activation of WIPK, a tobacco
      mitogen-activated protein kinase.
AB  - A gene encoding a tobacco mitogen-activated protein kinase (WIPK) is
      transcriptionally activated in response to wounding. Transgenic tobacco plants,
      in which expression of endogenous wipk was suppressed, did not accumulate
      jasmonic acid or its methyl ester when wounded, suggesting that WIPK is involved
      in jasmonate-mediated wound signal transduction. Here, we demonstrate that
      activation of WIPK is required for triggering the jasmonate-mediated signal
      transduction cascade that occurs when wild-type tobacco plants are wounded. We
      also show that when plants are wounded, WIPK is rapidly and transiently
      activated, whereas the quantity of WIPK protein is maintained at a constant
      level. A transgenic tobacco plant in which the wipk gene was constitutively
      expressed at a high level showed constitutive enzymatic activation of WIPK and
      exhibited three- to fourfold higher levels of jasmonate than did its wild-type
      counterpart. This plant also showed constitutive accumulation of jasmonate
      inducible proteinase inhibitor II transcripts. These results show that WIPK is
      activated in response to wounding, which subsequently causes an increase in
      jasmonate synthesis.

PMID- 9927647
TI  - Disease transmission dynamics and the evolution of antibiotic resistance in
      hospitals and communal settings.

PMID- 9927646
TI  - Tet B or not tet B: advances in tetracycline-inducible gene expression.

PMID- 9927648
TI  - Xenotropism: the elusive viral receptor finally uncovered.

PMID- 9927649
TI  - Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal
      targeting in cholesterol mobilization.
AB  - Niemann-Pick type C (NPC) disease is an inherited lipid storage disorder that
      affects the viscera and central nervous system. A characteristic feature of NPC
      cells is the lysosomal accumulation of low density lipoprotein-derived
      cholesterol. To elucidate important structural features of the recently
      identified NPC1 gene product defective in NPC disease, we examined the ability of
      wild-type NPC1 and NPC1 mutants to correct the excessive lysosomal storage of low
      density lipoprotein-derived cholesterol in a model cell line displaying the NPC
      cholesterol-trafficking defect (CT60 Chinese hamster ovary cells). CT60 cells
      transfected with human wild-type NPC1 contained immunoreactive proteins of 170
      and 190 kDa localized to the lysosomal/endosomal compartment. Wild-type NPC1
      protein corrected the NPC cholesterol-trafficking defect in the CT60 cells.
      Mutation of conserved cysteine residues in the NPC1 N terminus to serine residues
      resulted in proteins targeted to lysosomal membranes encircling cholesterol-laden
      cores, whereas deletion of the C-terminal 4-aa residues containing the LLNF
      lysosome-targeting motif resulted in the expression of protein localized to the
      endoplasmic reticulum. None of these mutant NPC1 proteins corrected the NPC
      cholesterol-trafficking defect in CT60 cells. We conclude that transport of the
      NPC1 protein to the cholesterol-laden lysosomal compartment is essential for
      expression of its biological activity and that domains in the N terminus of the
      NPC1 protein are critical for mobilization of cholesterol from lysosomes.

PMID- 9927650
TI  - Origins of DNA-binding specificity: role of protein contacts with the DNA
      backbone.
AB  - A central question in protein-DNA recognition is the origin of the specificity
      that permits binding to the correct site in the presence of excess, nonspecific
      DNA. In the P22 Arc repressor, the Phe-10 side chain is part of the hydrophobic
      core of the free protein but rotates out to pack against the sugar-phosphate
      backbone of the DNA in the repressor-operator complex. Characterization of a
      library of position 10 variants reveals that Phe is the only residue that results
      in fully active Arc. One class of mutants folds stably but binds operator with
      reduced affinity; another class is unstable. FV10, one member of the first class,
      binds operator DNA and nonoperator DNA almost equally well. The affinity
      differences between FV10 and wild type indicate that each Phe-10 side chain
      contributes 1.5-2.0 kcal to operator binding but less than 0.5 kcal/mol to
      nonoperator binding, demonstrating that contacts between Phe-10 and the operator
      DNA backbone contribute to binding specificity. This appears to be a direct
      contribution as the crystal structure of the FV10 dimer is similar to wild type
      and the Phe-10-DNA backbone interactions are the only contacts perturbed in the
      cocrystal structure of the FV10-operator complex.

PMID- 9927651
TI  - Trimeric domain-swapped barnase.
AB  - The structure of a trimeric domain-swapped form of barnase (EC 3.1. 27.3) was
      determined by x-ray crystallography at a resolution of 2.2 A from crystals of
      space group R32. Residues 1-36 of one molecule associate with residues 41-110
      from another molecule related through threefold symmetry. The resulting cyclic
      trimer contains three protein folds that are very similar to those in monomeric
      barnase. Both swapped domains contain a nucleation site for folding. The
      formation of a domain-swapped trimer is consistent with the description of the
      folding process of monomeric barnase as the formation and subsequent association
      of two foldons.

PMID- 9927652
TI  - Three-dimensional structure of phosphoenolpyruvate carboxylase: a proposed
      mechanism for allosteric inhibition.
AB  - The crystal structure of phosphoenolpyruvate carboxylase (PEPC; EC 4. 1.1.31) has
      been determined by x-ray diffraction methods at 2.8-A resolution by using
      Escherichia coli PEPC complexed with L-aspartate, an allosteric inhibitor of all
      known PEPCs. The four subunits are arranged in a "dimer-of-dimers" form with
      respect to subunit contact, resulting in an overall square arrangement. The
      contents of alpha-helices and beta-strands are 65% and 5%, respectively. All of
      the eight beta-strands, which are widely dispersed in the primary structure,
      participate in the formation of a single beta-barrel. Replacement of a conserved
      Arg residue (Arg-438) in this linkage with Cys increased the tendency of the
      enzyme to dissociate into dimers. The location of the catalytic site is likely to
      be near the C-terminal side of the beta-barrel. The binding site for L-aspartate
      is located about 20 A away from the catalytic site, and four residues (Lys-773,
      Arg-832, Arg-587, and Asn-881) are involved in effector binding. The
      participation of Arg-587 is unexpected, because it is known to be catalytically
      essential. Because this residue is in a highly conserved glycine-rich loop, which
      is characteristic of PEPC, L-aspartate seemingly causes inhibition by removing
      this glycine-rich loop from the catalytic site. There is another mobile loop from
      Lys-702 to Gly-708 that is missing in the crystal structure. The importance of
      this loop in catalytic activity was also shown. Thus, the crystal-structure
      determination of PEPC revealed two mobile loops bearing the enzymatic functions
      and accompanying allosteric inhibition by L-aspartate.

PMID- 9927653
TI  - Xenopus laevis sperm receptor gp69/64 glycoprotein is a homolog of the mammalian
      sperm receptor ZP2.
AB  - Little is known about sperm-binding proteins in the egg envelope of nonmammalian
      vertebrate species. We report here the molecular cloning and characterization of
      a recently identified sperm receptor (gp69/64) in the Xenopus laevis egg
      vitelline envelope. Our data indicate that the gp69 and gp64 glycoproteins are
      two glycoforms of the receptor and have the same number of N-linked
      oligosaccharide chains but differ in the extent of O-glycosylation. The amino
      acid sequence of the receptor is closely related to that of the mouse zona
      pellucida protein ZP2. Most of the sequence conservation, including a ZP domain,
      a potential furin cleavage site, and a putative transmembrane domain are located
      in the C-terminal half of the receptor. Proteolytic cleavage of the gp69/64
      protein by a cortical granule protease during fertilization removes 27 amino acid
      residues from the N terminus of gp69/64 and results in loss of sperm binding to
      the activated eggs. Similarly, we find that treatment of eggs with type I
      collagenase removes 31 residues from the N terminus of gp69/64 and has the same
      effect on sperm binding. The isolated and purified N terminus-truncated receptor
      protein is inactive as an inhibitor of sperm-egg binding. Earlier studies on the
      effect of Pronase digestion on receptor activity suggest that this N-terminal
      peptide may contain an O-linked glycan that is involved in the binding process.
      Based on these results and the findings on the primary structure of the receptor,
      a pathway for the maturation and secretion of gp69/64, as well as its
      inactivation following fertilization, is proposed.

PMID- 9927654
TI  - Levels of major selenoproteins in T cells decrease during HIV infection and low
      molecular mass selenium compounds increase.
AB  - It has been observed previously that plasma selenium and glutathione levels are
      subnormal in HIV-infected individuals, and plasma glutathione peroxidase activity
      is decreased. Under these conditions the survival rate of AIDS patients is
      reduced significantly. In the present study, using 75Se-labeled human Jurkat T
      cells, we show that the levels of four 75Se-containing proteins are lower in HIV
      infected cell populations than in uninfected cells. These major selenoproteins
      migrated as 57-, 26-, 21-, and 15-kDa species on SDS/PAGE gels. In our earlier
      studies, the 57-kDa protein was purified from T cells and identified as a subunit
      of thioredoxin reductase. The 26- and 21-kDa proteins were identified in
      immunoblot assays as the glutathione peroxidase (cGPX or GPX1) subunit and
      phospholipid hydroperoxide glutathione peroxidase (PHGPX or GPX4), respectively.
      We recently purified the 15-kDa protein and characterized it as a selenoprotein
      of unknown function. In contrast to selenoproteins, low molecular mass
      [75Se]compounds accumulated during HIV infection and migrated as a diffuse band
      near the front of SDS/PAGE gels.

PMID- 9927655
TI  - Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase
      type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+.
AB  - Excess 17beta-estradiol (E2), the most potent of human estrogens, is known to act
      as a stimulus for the growth of breast tumors. Human estrogenic 17beta
      hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction
      of inactive estrone (E1) to the active 17beta-estradiol in breast tissues, is a
      key enzyme responsible for elevated levels of E2 in breast tumor tissues. We
      present here the structure of the ternary complex of 17beta-HSD1 with the
      cofactor NADP+ and 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin), an equine
      estrogen used in estrogen replacement therapy. The ternary complex has been
      crystallized with a homodimer, the active form of the enzyme, in the asymmetric
      unit. Structural and kinetic data presented here show that the 17beta-HSD1
      catalyzed reduction of E1 to E2 in vitro is specifically inhibited by equilin.
      The crystal structure determined at 3.0-A resolution reveals that the equilin
      molecule is bound at the active site in a mode similar to the binding of
      substrate. The orientation of the 17-keto group with respect to the nicotinamide
      ring of NADP+ and catalytic residues Tyr-155 and Ser-142 is different from that
      of E2 in the 17beta-HSD1-E2 complex. The ligand and substrate-entry loop
      densities are well defined in one subunit. The substrate-entry loop adopts a
      closed conformation in this subunit. The result demonstrates that binding of
      equilin at the active site of 17beta-HSD1 is the basis for inhibition of E1-to-E2
      reduction by this equine estrogen in vitro. One possible outcome of estrogen
      replacement therapy in vivo could be reduction of E2 levels in breast tissues and
      hence the reduced risk of estrogen-dependent breast cancer.

PMID- 9927657
TI  - U1 small nuclear RNA and spliceosomal introns in Euglena gracilis.
AB  - In the flagellated protozoon Euglena gracilis, characterized nuclear genes harbor
      atypical introns that usually are flanked by short repeats, adopt complex
      secondary structures in pre-mRNA, and do not obey the GT-AG rule of conventional
      cis-spliced introns. In the nuclear fibrillarin gene of E. gracilis, we have
      identified three spliceosomal-type introns that have GT-AG consensus borders.
      Furthermore, we have isolated a small RNA from E. gracilis and propose, on the
      basis of primary and secondary structure comparisons, that it is a homolog of U1
      small nuclear RNA, an essential component of the cis-spliceosome in higher
      eukaryotes. Conserved sequences at the 5' splice sites of the fibrillarin introns
      can potentially base pair with Euglena U1 small nuclear RNA. Our observations
      demonstrate that spliceosomal GT-AG cis-splicing occurs in Euglena, in addition
      to the nonconventional cis-splicing and spliced leader trans-splicing previously
      recognized in this early diverging unicellular eukaryote.

PMID- 9927656
TI  - Mitochondrial disease in superoxide dismutase 2 mutant mice.
AB  - Oxidative stress has been implicated in many diseases. The chief source of
      reactive oxygen species within the cell is the mitochondrion. We have
      characterized a variety of the biochemical and metabolic effects of inactivation
      of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1Cje)).
      The Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory
      chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex
      II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development
      of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3
      methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage. These results
      indicate that the increase in mitochondrial reactive oxygen species can result in
      biochemical aberrations with features reminiscent of mitochondrial myopathy,
      Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

PMID- 9927658
TI  - The specificity of interaction of archaeal transducers with their cognate sensory
      rhodopsins is determined by their transmembrane helices.
AB  - Chimeras of the Halobacterium salinarum transducers HtrI and HtrII were
      constructed to study the structural determinants for their specific interaction
      with the phototaxis receptors sensory rhodopsins I and II (SRI and SRII),
      respectively. Interaction of receptors and transducers was assessed by two
      criteria: phototaxis responses by the cells and transducer-modulation of receptor
      photochemical reaction kinetics in membranes. Coexpression of HtrI with SRII or
      HtrII with SRI did not result in interaction by either criterion. Each receptor
      was coexpressed with chimeric transducers in which various domains of the two
      transducers were interchanged. The results show that the presence of the two
      transmembrane helices of HtrI in a chimera is necessary and sufficient for
      functional transducer complexation with SRI, i.e., for wild-type SRI
      photoreactions and attractant and 2-photon repellent phototaxis responses.
      Additionally, a previously demonstrated chaperone-like facilitation of SRI
      folding or stability by HtrI was shown to depend only on the two transmembrane
      helices of HtrI in chimeric transducers. Similarly, the two transmembrane helices
      of HtrII specify interaction with the repellent receptor SRII according to
      motility analysis and laser-flash spectroscopy. The results support a model in
      which the membrane domains of the receptor/transducer complexes, consisting of
      the seven helices of the receptor interacting with the four-helix bundle of the
      transducer dimer, produce SRI- and SRII-specific signals to the flagellar motor
      by means of interchangeable cytoplasmic domains.

PMID- 9927659
TI  - TOXCAT: a measure of transmembrane helix association in a biological membrane.
AB  - The noncovalent association of transmembrane alpha-helices is a fundamental event
      in the folding of helical membrane proteins. In this work, a system (TOXCAT) is
      developed for the study of transmembrane helix-helix oligomerization in a natural
      membrane environment. This assay uses a chimeric construct composed of the N
      terminal DNA binding domain of ToxR (a dimerization-dependent transcriptional
      activator) fused to a transmembrane domain (tm) of interest and a monomeric
      periplasmic anchor (the maltose binding protein). Association of the tms results
      in the ToxR-mediated activation of a reporter gene encoding chloramphenicol
      acetyltransferase (CAT). The level of CAT expression indicates the strength of tm
      association. The assay distinguishes between a known dimerizing tm and a mutant
      in which dimerization is disrupted. In addition, modulation of the chimera
      concentration shows that the dimerization exhibits concentration dependence in
      membranes. TOXCAT also is used to select oligomeric tms from a library of
      randomized sequences, demonstrating the potential of this system to reveal novel
      oligomerization motifs. The TOXCAT system has been used to investigate
      glycophorin A tm-mediated dimerization. Although the overall sensitivity of
      glycophorin A tm dimerization to mutagenesis is found to be similar in membranes
      and in detergent micelles, several significant differences exist. Mutations to
      polar residues, which are generally disruptive in SDS, exhibit sequence
      specificity in membranes, demonstrating both the limitations of detergent
      micelles and the wider range of application of the TOXCAT system.

PMID- 9927660
TI  - The C-terminal domain of the regulatory protein NOVH is sufficient to promote
      interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion
      signaling.
AB  - The NOVH protein belongs to the emerging CCN [Connective tissue growth factor
      (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth
      regulators sharing a strikingly conserved multimodular organization but
      exhibiting distinctive functional features. Two members of the family (CYR61 and
      CTGF) are positive regulators of cell proliferation, whereas NOVH and two other
      members (ELM1 and RCOP-1) exhibit features of negative regulators of growth. The
      multimodular structure of these proteins suggests that their biological role(s)
      may depend on interactions with several factors as well as proteins constitutive
      of the extracellular matrix. To gain insight into the functionality of these
      domains, we have used a two-hybrid system to identify proteins interacting with
      NOVH. We report here that the C-terminal domain confers on the full-length NOVH
      protein the capacity to bind fibulin 1C, a protein of the extracellular matrix
      that interacts with several other regulators of cell adhesion. Furthermore, we
      show that a natural N-truncated isoform of NOVH produced by cells expressing the
      full-length NOVH protein also binds fibulin 1C with a high affinity, and we
      hypothesize that the production of truncated isoforms of NOVH (and probably of
      other CCN proteins) may be a critical aspect in the modulation of their
      biological activity. These results set the stage for a study of NOVH-fibulin 1C
      interactions and their potential significance in cell-adhesion signaling in
      normal and pathological conditions.

PMID- 9927661
TI  - Induced fit of a peptide loop of methionyl-tRNA formyltransferase triggered by
      the initiator tRNA substrate.
AB  - A 16-aa insertion loop present in eubacterial methionyl-tRNA formyltransferases
      (MTF) is critical for specific recognition of the initiator tRNA in Escherichia
      coli. We have studied the interactions between this region of the E. coli enzyme
      and initiator methionyl-tRNA (Met-tRNA) by using two complementary protection
      experiments: protection of MTF against proteolytic cleavage by tRNA and
      protection of tRNA against nucleolytic cleavage by MTF. The insertion loop in MTF
      is uniquely sensitive to cleavage by trypsin. We show that the substrate
      initiator Met-tRNA protects MTF against trypsin cleavage, whereas a formylation
      defective mutant initiator Met-tRNA, which binds to MTF with approximately the
      same affinity, does not. Also, mutants of MTF within the insertion loop (which
      are defective in formylation) are not protected by the initiator Met-tRNA. Thus,
      a functional enzyme-substrate complex is necessary for protection of MTF against
      trypsin cleavage. Along with other data, these results strongly suggest that a
      segment of the insertion loop, which is exposed and unstructured in MTF,
      undergoes an induced fit in the functional MTF.Met-tRNA complex but not in the
      nonfunctional one. Footprinting experiments show that MTF specifically protects
      the acceptor stem and the 3'-end region of the initiator Met-tRNA against
      cleavage by double and single strand-specific nucleases. This protection also
      depends on formation of a functional MTF.Met-tRNA complex. Thus, the insertion
      loop interacts mostly with the acceptor stem of the initiator Met-tRNA, which
      contains the critical determinants for formylation.

PMID- 9927662
TI  - Similarity in the catalysis of DNA breakage and rejoining by type IA and IIA DNA
      topoisomerases.
AB  - Studies of yeast DNA topoisomerase II with various alanine-substitution mutations
      provide strong biochemical support of a recent hypothesis that the type IA and
      IIA DNA topoisomerases act similarly in their cleavage and rejoining of DNA. DNA
      breakage and rejoining by either a type IA or a type IIA enzyme are shown to
      involve cooperation between a DNA-binding domain containing the active-site
      tyrosine and a Rossmann fold containing several highly conserved acidic residues.
      For a homodimeric type IIA enzyme, cooperation occurs in trans: the active-site
      tyrosine in the DNA-binding domain of one protomer cooperates with several
      residues in the Rossmann fold as well as other regions of the other protomer.

PMID- 9927663
TI  - The minimal gene set member msrA, encoding peptide methionine sulfoxide
      reductase, is a virulence determinant of the plant pathogen Erwinia chrysanthemi.
AB  - Peptide methionine sulfoxide reductase (MsrA), which repairs oxidized proteins,
      is present in most living organisms, and the cognate structural gene belongs to
      the so-called minimum gene set [Mushegian, A. R. & Koonin, E. V., (1996) Proc.
      Natl. Acad. Sci. USA 93, 10268-10273]. In this work, we report that MsrA is
      required for full virulence of the plant pathogen Erwinia chrysanthemi. The
      following differences were observed between the wild-type and a MsrA- mutant: (i)
      the MsrA- mutant was more sensitive to oxidative stress; (ii) the MsrA- mutant
      was less motile on solid surface; (iii) the MsrA- mutant exhibited reduced
      virulence on chicory leaves; and (iv) no systemic invasion was observed when the
      MsrA- mutant was inoculated into whole Saintpaulia ionantha plants. These results
      suggest that plants respond to virulent pathogens by producing active oxygen
      species, and that enzymes repairing oxidative damage allow virulent pathogens to
      survive the host environment, thereby supporting the theory that active oxygen
      species play a key role in plant defense.

PMID- 9927664
TI  - Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and
      cleavage mechanism.
AB  - Fluorescence resonance energy transfer and fluorescence polarization anisotropy
      are used to investigate single molecules of the enzyme staphylococcal nuclease.
      Intramolecular fluorescence resonance energy transfer and fluorescence
      polarization anisotropy measurements of fluorescently labeled staphylococcal
      nuclease molecules reveal distinct patterns of fluctuations that may be
      attributed to protein conformational dynamics on the millisecond time scale.
      Intermolecular fluorescence resonance energy transfer measurements provide
      information about the dynamic interactions of staphylococcal nuclease with single
      substrate molecules. The experimental methods demonstrated here should prove
      generally useful in studies of protein folding and enzyme catalysis at single
      molecule resolution.

PMID- 9927665
TI  - Enhanced rate of intramolecular electron transfer in an engineered purple CuA
      azurin.
AB  - The recent expression of an azurin mutant where the blue type 1 copper site is
      replaced by the purple CuA site of Paracoccus denitrificans cytochrome c oxidase
      has yielded an optimal system for examining the unique electron mediation
      properties of the binuclear CuA center, because both type 1 and CuA centers are
      placed in the same location in the protein while all other structural elements
      remain the same. Long-range electron transfer is induced between the disulfide
      radical anion, produced pulse radiolytically, and the oxidized binuclear CuA
      center in the purple azurin mutant. The rate constant of this intramolecular
      process, kET = 650 +/- 60 s-1 at 298 K and pH 5.1, is almost 3-fold faster than
      for the same process in the wild-type single blue copper azurin from Pseudomonas
      aeruginosa (250 +/- 20 s-1), in spite of a smaller driving force (0.69 eV for
      purple CuA azurin vs. 0.76 eV for blue copper azurin). The reorganization energy
      of the CuA center is calculated to be 0.4 eV, which is only 50% of that found for
      the wild-type azurin. These results represent a direct comparison of electron
      transfer properties of the blue and purple CuA sites in the same protein
      framework and provide support for the notion that the binuclear purple CuA center
      is a more efficient electron transfer agent than the blue single copper center
      because reactivity of the former involves a lower reorganization energy.

PMID- 9927666
TI  - Alpha-helix nucleation by a calcium-binding peptide loop.
AB  - A 12-residue peptide AcDKDGDGYISAAENH2 analogous to the third calcium-binding
      loop of calmodulin strongly coordinates lanthanide ions (K = 10(5) M-1). When
      metal saturated, the peptide adopts a very rigid structure, the same as in the
      native protein, with three last residues AAE fixed in the alpha-helical
      conformation. Therefore, the peptide provides an ideal helix nucleation site for
      peptide segments attached to its C terminus. NMR and CD investigations of peptide
      AcDKDGDGYISAAEAAAQNH2 presented in this paper show that residues A13-Q16 form an
      alpha-helix of very high stability when the La3+ ion is bound to the D1-E12 loop.
      In fact, the lowest estimates of the helix content in this segment give values of
      at least 80% at 1 degreesC and 70% at 25 degreesC. This finding is not compatible
      with existing helix-coil transition theories and helix propagation parameters, s,
      reported in the literature. We conclude, therefore, that the initial steps of
      helix propagation are characterized by much larger s values, whereas helix
      nucleation is even more unfavorable than is believed. In light of our findings,
      thermodynamics of the nascent alpha-helices is discussed. The problem of CD
      spectra of very short alpha-helices is also addressed.

PMID- 9927667
TI  - SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1,
      regulates exocytosis and pseudohyphal differentiation in yeast.
AB  - The exocyst is an essential multiprotein complex mediating polarized secretion in
      yeast. Here we describe a gene, SEM1, that can multicopy-suppress exocyst mutants
      sec3-2, sec8-9, sec10-2, and sec15-1. SEM1 is highly conserved among eukaryotic
      species. Its human homologue, DSS1, has been suggested as a candidate gene for
      the split hand/split foot malformation disorder. SEM1 is not an essential gene.
      However, its deletion rescued growth of the temperature-sensitive exocyst mutants
      sec3-2, sec8-9, sec10-1, and sec15-1 at the restrictive temperature. Cell
      fractionation showed that Sem1p is mainly cytosolic but also associates with the
      microsomal fraction. In linear sucrose gradients, Sem1p cosedimented with the
      exocyst component Sec8p. In diploid cells that normally do not form pseudohyphae
      (S288C background), deletion of SEM1 triggered pseudohyphal growth. This
      phenotype was abolished after reintroduction of either SEM1 or the mouse
      homologue Dss1 into the cells. In diploids that have normal capacity for
      pseudohyphal growth (Sigma1278b background), deletion of SEM1 enhanced
      filamentous growth. The functionality of both SEM1 and Dss1 in a differentiation
      process in yeast suggests that Dss1 indeed could be the gene affected in the
      split hand/split foot malformation disorder. These results characterize SEM1 as a
      regulator of both exocyst function and pseudohyphal differentiation and suggest a
      unique link between these two cellular functions in yeast.

PMID- 9927668
TI  - Expression cloning of LDLB, a gene essential for normal Golgi function and
      assembly of the ldlCp complex.
AB  - The Chinese hamster ovary (CHO) cell mutants ldlC and ldlB, which exhibit almost
      identical phenotypes, define two genes required for multiple steps in the normal
      medial and trans Golgi-associated processing of glycoconjugates. The LDLC gene
      encodes ldlCp, an approximately 80-kDa protein, which in wild-type, but not ldlB,
      cells associates reversibly with the cytoplasmic surface of the Golgi apparatus.
      Here, we have used a retrovirus-based expression cloning system to clone a murine
      cDNA, LDLB, that corrects the pleiotropic mutant phenotypes of ldlB cells. The
      corresponding mRNA was not detected in ldlB mutants. LDLB encodes an
      approximately 110-kDa protein, ldlBp, which lacks homology to known proteins and
      contains no common structural motifs. Database searches identified short segments
      of homology to sequences from Drosophila melanogaster, Arabidopsis thaliana, and
      Caenorhabditis elegans, and the essentially full-length homologous human sequence
      (82% identity); however, as was the case for ldlCp, no homologue was identified
      in Saccharomyces cerevisiae. We have found that in wild-type cell cytosols, ldlCp
      is a component of an approximately 950-kDa "ldlCp complex," which is smaller,
      approximately 700 kDa, in ldlB cytosols. Normal assembly of this complex is ldlBp
      dependent and may be required for Golgi association of ldlCp and for the normal
      activities of multiple luminal Golgi processes.

PMID- 9927669
TI  - Dimensional and mechanical dynamics of active and stable edges in motile
      fibroblasts investigated by using atomic force microscopy.
AB  - The atomic force microscope (AFM) was employed to investigate the extension and
      retraction dynamics of protruding and stable edges of motile 3T3 fibroblasts in
      culture. Such dynamics closely paralleled the results of earlier studies
      employing video microscopy that indicated that the AFM force-mapping technique
      does not appreciably perturb these dynamics. Force scans permitted height
      determinations of active and stable edges. Whereas the profiles of active edges
      are flat with average heights of 0.4-0.8 micrometer, stable edges smoothly ascend
      to 2-3 micrometers within about 6 micrometers of the edge. In the region of the
      leading edge, the height fluctuates up to 50% (SD) of the mean value, much more
      than the stable edge; this fluctuation presumably reflects differences in
      underlying cytoskeletal activity. In addition, force mapping yields an estimate
      of the local Young's modulus or modulus of elasticity (E, the cortical
      stiffness). This stiffness will be related to "cortical tension," can be
      accurately calculated for the stable edges, and is approximately 12 kPa in this
      case. The thinness of the leading edge precludes accurate estimation of the E
      values, but within 4 micrometers of the margin it is considerably smaller than
      that for stable edges, which have an upper limit of 3-5 kPa. Although blebbing
      cannot absolutely be ruled out as a mechanism of extension, the data are
      consistent with an actin polymerization and/or myosin motor mechanism in which
      the average material properties of the extending margin would be nearly constant
      to the edge. Because the leading edge is softer than the stable edge, these data
      also are consistent with the notion that extension preferentially occurs in
      regions of lower cortical tension.

PMID- 9927670
TI  - Cloning and characterization of a cell surface receptor for xenotropic and
      polytropic murine leukemia viruses.
AB  - Xenotropic and polytropic murine leukemia viruses (X-MLVs and P-MLVs) cross
      interfere to various extents in non-mouse species and in wild Asian mice,
      suggesting that they might use a common receptor for infection. Consistent with
      this hypothesis, the susceptibility of some wild mice to X-MLVs has been mapped
      to the P-MLV receptor locus at the distal end of mouse chromosome 1. In this
      study, we report the isolation and characterization of a cDNA for the human X-MLV
      cell surface receptor (X-receptor) by using a human T lymphocyte cDNA library in
      a retroviral vector. The predicted X-receptor contains 696 amino acids with
      multiple hydrophobic potential membrane-spanning sequences and with weak
      homologies to the yeast proteins SYG1, of unknown function, and PHO81, which has
      been implicated in a system that regulates transport of inorganic phosphate.
      Expression of the X-receptor in Chinese hamster ovary cells, which are
      substantially resistant to P-MLVs and to X-MLVs, made them susceptible to both of
      these virus groups. The mouse homologue of the X-receptor was mapped by
      hybridization to the distal end of chromosome 1 at the same position as the P-MLV
      receptor gene Rmc1. These results strongly support the hypothesis that a common
      gene encodes the receptors for X-MLVs and P-MLVs, with the human X-receptor
      preferentially mediating X-MLV infections and the homologous protein of inbred
      mice mediating only P-MLV infections. We propose that X-MLVs and P-MLVs comprise
      a single family of retroviruses that have coevolved in response to
      diversification in X-receptor genes of the host.

PMID- 9927671
TI  - The nuclear matrix prepared by amine modification.
AB  - The nucleus is spatially ordered by attachments to a nonchromatin nuclear
      structure, the nuclear matrix. The nuclear matrix and chromatin are intimately
      connected and integrated structures, and so a major technical challenge in
      nuclear matrix research has been to remove chromatin while retaining a native
      nuclear matrix. Most methods for removing chromatin require first a nuclease
      digestion and then a salt extraction to remove cut chromatin. We have
      hypothesized that cut chromatin is held in place by charge interactions involving
      nucleosomal amino groups. We have tested this hypothesis by chemically modifying
      amino groups after nuclease digestion. By using this protocol, chromatin could be
      effectively removed at physiological ionic strength. We compared the
      ultrastructure and composition of this nuclear matrix preparation with the
      traditional high-salt nuclear matrix and with the third nuclear matrix
      preparation that we have developed from which chromatin is removed after
      extensive crosslinking. All three matrix preparations reveal internal nuclear
      matrix structures that are built on a network of branched filaments of about 10
      nm diameter. That such different chromatin-removal protocols reveal similar
      principles of nuclear matrix construction increases our confidence that we are
      observing important architectural elements of the native structure in the living
      cell.

PMID- 9927672
TI  - Model of maltose-binding protein/chemoreceptor complex supports intrasubunit
      signaling mechanism.
AB  - The Tar protein of Escherichia coli is unique among known bacterial
      chemoreceptors in that it generates additive responses to two very disparate
      ligands, aspartate and maltose. Aspartate binds directly to the periplasmic
      (extracytoplasmic) domain of Tar. Maltose first binds to maltose-binding protein
      (MBP). MBP then assumes a closed conformation in which it can interact with the
      periplasmic domain of Tar. MBP residues critical for binding Tar were identified
      in a screen of mutations that cause specific defects in maltose chemotaxis.
      Mutations were introduced into a plasmid-borne malE gene that encodes a mutant
      form of MBP in which two engineered Cys residues spontaneously generate a
      disulfide bond in the oxidizing environment of the periplasmic space. This
      disulfide covalently crosslinks the NH3-terminal and COOH-terminal domains of MBP
      and locks the protein into a closed conformation. Double-Cys MBP confers a
      dominant-negative phenotype for maltose taxis, and we reasoned that third
      mutations that relieve this negative dominance probably alter residues that are
      important for the initial interaction of MBP with Tar. The published three
      dimensional structures of MBP and the periplasmic domain of E. coli Tar were
      docked in a computer simulation that juxtaposed the residues in MBP identified in
      this way with residues in Tar that have been implicated in maltose taxis. The
      resulting model of the MBP-Tar complex exhibits good complementarity between the
      surfaces of the two proteins and supports the idea that aspartate and MBP may
      each initiate an attractant signal through Tar by inducing similar conformational
      changes in the chemoreceptor.

PMID- 9927673
TI  - Multiple and diverse forms of regulated exocytosis in wild-type and defective
      PC12 cells.
AB  - Regulated exocytosis triggered by the photolysis of a caged Ca2+ compound, DM
      nitrophen, was investigated by patch-clamp capacitance measurements in two clones
      of PC12, the first wild-type and the second (PC12-27) defective of both types of
      classical secretory vesicles together with the neuronal-type receptors for the
      attachment proteins of the N-ethylmaleimide-sensitive fusion protein, the so
      called SNAREs. Moreover, the electrophysiological data were correlated with the
      ultrastructure of resting quick-frozen-freeze-dried cells of the two clones. Wild
      type PC12 exhibited two-component capacitance responses, time constants of 30-100
      ms and >10 s, that previous studies had suggested to reflect primarily the fusion
      of the small and large secretory vesicles, each contributing cell surface
      increases of approximately 10%. Both of these components were largely and
      specifically inhibited whether cells previously were microinjected with tetanus
      toxin light chain. In the defective clone, large responses also were recorded (
      approximately 19% surface expansion; time constant, approximately 1 s) that, in
      contrast to those of the wild-type, were entirely resistant to the toxin.
      Although secretory organelles, i.e., large vesicles and also profiles of small
      vesicles, were abundant at the cell periphery and often docked to the plasmalemma
      of resting wild-type PC12, in the defective clone, no superficial accumulation of
      vesicles was observed. Our coordinate structural and functional results have
      revealed diversities between the two classical forms of regulated secretion in
      wild-type PC12 and have provided evidence of a toxin-insensitive form of Ca2+
      induced exocytosis, prominent in the defective clone, that may play an important
      role(s) in cellular physiology.

PMID- 9927674
TI  - FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins
      Friend of GATA-1 and U-shaped.
AB  - GATA factors are transcriptional regulatory proteins that play critical roles in
      the differentiation of multiple cell types in both vertebrates and invertebrates.
      Recent evidence suggests that the biological activities of both mammalian and
      Drosophila GATA factors are controlled in part by physical interaction with
      multitype zinc-finger proteins, Friend of GATA-1 (FOG) and U-shaped (Ush),
      respectively. Here we describe a new FOG-related polypeptide, designated FOG-2,
      that is likely to participate in differentiation mediated by GATA factors in
      several tissues. Expression of FOG-2 mRNA differs from that of FOG and is largely
      restricted to heart, neurons, and gonads in the adult. Somewhat broader
      expression is evident during mouse embryonic development. Similar to FOG and Ush,
      FOG-2 protein interacts specifically with the amino finger of GATA factors in the
      yeast two-hybrid system and in mammalian cells. Remarkably, though FOG-2 is quite
      divergent from FOG in its primary sequence, forced expression of FOG-2 rescues
      terminal erythroid maturation of FOG-/- hematopoietic cells. Thus, members of the
      FOG family of cofactors share highly specific association with GATA factors and
      are substantially interchangeable with respect to some aspects of function in
      vivo. The interaction of GATA and FOG family members constitutes an
      evolutionarily conserved paradigm for transcriptional control in differentiation
      and organogenesis.

PMID- 9927675
TI  - Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in
      cardiomyocytes.
AB  - GATA transcription factors are important regulators of both hematopoiesis (GATA
      1/2/3) and cardiogenesis (GATA-4) in mammals. The transcriptional activities of
      the GATA proteins are modulated by their interactions with other transcription
      factors and with transcriptional coactivators and repressors. Recently, two
      related zinc finger proteins, U-shaped (USH) and Friend of GATA-1 (FOG) have been
      reported to interact with the GATA proteins Pannier and GATA-1, respectively, and
      to modulate their transcriptional activities in vitro and in vivo. In this
      report, we describe the molecular cloning and characterization of a third FOG
      related protein, FOG-2. FOG-2 is an 1,151 amino acid nuclear protein that
      contains eight zinc finger motifs that are structurally related to those of both
      FOG and USH. FOG-2 is first expressed in the mouse embryonic heart and septum
      transversum at embryonic day 8.5 and is subsequently expressed in the developing
      neuroepithelium and urogenital ridge. In the adult, FOG-2 is expressed
      predominately in the heart, brain, and testis. FOG-2 associates physically with
      the N-terminal zinc finger of GATA-4 both in vitro and in vivo. This interaction
      appears to modulate specifically the transcriptional activity of GATA-4 because
      overexpression of FOG-2 in both NIH 3T3 cells and primary rat cardiomyocytes
      represses GATA-4-dependent transcription from multiple cardiac-restricted
      promoters. Taken together, these results implicate FOG-2 as a novel modulator of
      GATA-4 function during cardiac development and suggest a paradigm in which tissue
      specific interactions between different FOG and GATA proteins regulate the
      differentiation of distinct mesodermal cell lineages.

PMID- 9927676
TI  - Metamorphosis is inhibited in transgenic Xenopus laevis tadpoles that overexpress
      type III deiodinase.
AB  - One of the genes that is up-regulated by thyroid hormone (TH) during Xenopus
      laevis metamorphosis encodes a type III deiodinase (D3) that inactivates TH.
      Transgenic X. laevis tadpoles overexpressing a GFP-D3 fusion protein were
      produced. These transgenic tadpoles had high levels of deiodinase activity and
      were resistant to exogenous TH added 1 week after fertilization. They developed
      normally throughout embryogenesis and premetamorphic stages but became retarded
      in their development late in prometamorphosis when endogenous TH reaches its
      highest level. Gill and tail resorption were delayed and most of the animals
      arrested and died. One tadpole completed its metamorphosis without resorbing its
      tail. These results demonstrate that D3 can modulate the action of TH in vivo,
      and document the value of the new transgenic method for functional analysis of
      genes involved in metamorphosis.

PMID- 9927677
TI  - sqv mutants of Caenorhabditis elegans are defective in vulval epithelial
      invagination.
AB  - By screening for mutations that perturb the invagination of the vulva of the
      Caenorhabditis elegans hermaphrodite, we have isolated 25 mutations that define
      eight genes. We have named these genes sqv-1 to sqv-8 (squashed vulva). All 25
      mutations cause the same vulval defect, an apparent partial collapse of the
      vulval invagination and an elongation of the central vulval cells. Most sqv
      mutations also cause an oocyte or somatic gonad defect that results in
      hermaphrodite sterility, and some sqv mutations cause maternal-effect lethality.
      We propose that the sqv genes affect a pathway common to vulval invagination,
      oocyte development, and embryogenesis.

PMID- 9927679
TI  - Perception of solar UVB radiation by phytophagous insects: behavioral responses
      and ecosystem implications.
AB  - Most of our present knowledge about the impacts of solar UVB radiation on
      terrestrial ecosystems comes from studies with plants. Recently, the effects of
      UVB on the growth and survival of consumer species have begun to receive
      attention, but very little is known about UVB impacts on animal behavior. Here we
      report that manipulations of the flux of solar UVB received by field-grown
      soybean crops had large and consistent effects on the density of the thrips
      (Caliothrips phaseoli, Thysanoptera: Thripidae) populations that invaded the
      canopies, as well as on the amount of leaf damage caused by the insects. Solar
      UVB strongly reduced thrips herbivory. Thrips not only preferred leaves from
      plants that were not exposed to solar UVB over leaves from UVB-exposed plants in
      laboratory and field choice experiments, but they also appeared to directly sense
      and avoid exposure to solar UVB. Additional choice experiments showed that
      soybean leaf consumption by the late-season soybean worm Anticarsia gemmatalis
      (Lepidoptera: Noctuidae) was much less intense in leaves with even slight
      symptoms of an early thrips attack than in undamaged leaves. These experiments
      suggest that phytophagous insects can present direct and indirect behavioral
      responses to solar UVB. The indirect responses are mediated by changes in the
      plant host that are induced by UVB and, possibly, by other insects whose behavior
      is affected by UVB.

PMID- 9927680
TI  - Interspecific and intraspecific competition as causes of direct and delayed
      density dependence in a fluctuating vole population.
AB  - A 3- to 5-year cycle of vole abundances is a characteristic phenomenon in the
      ecology of northern regions, and their explanation stands as a central
      theoretical challenge in population ecology. Although many species of voles
      usually coexist and are in severe competition for food and breeding space, the
      role of interspecific competition in vole cycles has never been evaluated
      statistically. After studying community effects on the population dynamics of the
      gray-sided vole (Clethrionomys rufocanus) in the subarctic birch forest at
      Kilpisjarvi, Finland, we report statistical results showing that both
      interspecific and intraspecific effects are important in the direct year-to-year
      density dependence. However, interspecific effects are not detectable in the 2
      year delayed density dependence that is crucial for generating the characteristic
      cycles. Furthermore, we show that most of the competition takes place during the
      winter. The results are evaluated against two models of community dynamics. One
      assumes that the delayed effects are caused by an interaction with a specialist
      predator, and the other assumes that they are caused by overgrazing food plants.
      These statistical results show that vole cycles may be generated by a species
      specific trophic interaction. The results also suggest that the gray-sided vole
      may be the focal species in the birch-forest community, as field voles may be in
      the taiga and as lemmings may be on the tundra.

PMID- 9927678
TI  - Three proteins involved in Caenorhabditis elegans vulval invagination are similar
      to components of a glycosylation pathway.
AB  - We have molecularly analyzed three genes, sqv-3, sqv-7, and sqv-8, that are
      required for wild-type vulval invagination in Caenorhabditis elegans. The
      predicted SQV-8 protein is similar in sequence to two mammalian beta(1,3)
      glucuronyltransferases, one of which adds glucuronic acid to protein-linked
      galactose-beta(1, 4)-N-acetylglucosamine. SQV-3 is similar to a family of
      glycosyltransferases that includes vertebrate beta(1, 4)-galactosyltransferases,
      which create galactose-beta(1, 4)-N-acetylglucosamine linkages. One model is
      therefore that SQV-8 uses a SQV-3 product as a substrate. SQV-7 is similar to
      members of a family of nucleotide-sugar transporters. The sqv genes therefore are
      likely to encode components of a conserved glycosylation pathway that assembles a
      C. elegans carbohydrate moiety, the absence of which perturbs vulval
      invagination.

PMID- 9927681
TI  - Species realities and numbers in sexual vertebrates: perspectives from an
      asexually transmitted genome.
AB  - A literature review is conducted on the phylogenetic discontinuities in mtDNA
      sequences of 252 taxonomic species of vertebrates. About 140 of these species
      (56%) were subdivided clearly into two or more highly distinctive matrilineal
      phylogroups, the vast majority of which were localized geographically. However,
      only a small number (two to six) of salient phylogeographic subdivisions (those
      that stand out against mean within-group divergences) characterized individual
      species. A previous literature summary showed that vertebrate sister species and
      other congeners also usually have pronounced phylogenetic distinctions in mtDNA
      sequence. These observations, taken together, suggest that current taxonomic
      species often agree reasonably well in number (certainly within an order-of
      magnitude) and composition with biotic entities registered in mtDNA genealogies
      alone. In other words, mtDNA data and traditional taxonomic assignments tend to
      converge on what therefore may be "real" biotic units in nature. All branches in
      mtDNA phylogenies are nonanastomose, connected strictly via historical genealogy.
      Thus, patterns of historical phylogenetic connection may be at least as important
      as contemporary reproductive relationships per se in accounting for
      microevolutionary unities and discontinuities in sexually reproducing
      vertebrates. Findings are discussed in the context of the biological and
      phylogenetic species concepts.

PMID- 9927682
TI  - Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas.
AB  - Mice with null mutations in the E2A gene are highly susceptible to the
      spontaneous development of thymic lymphomas. To understand better how E2A
      deficiency may contribute to lymphomagenesis, we have observed the consequences
      of enforced expression of the E2A gene products E12 and E47 in cell lines derived
      from lymphomas that arose spontaneously in E2A-deficient mice. E2A-expressing
      cells are steadily eliminated from lymphoma cultures into which E47 or E12 was
      introduced. The mechanism underlying the loss of E2A-expressing cells does not
      involve an arrest in cell-cycle progression. Rather, the E2A proteins activate a
      programmed cell death pathway in these lymphomas. This E2A-mediated cell death
      appears to be preceded by a loss of mitochondrial transmembrane potential. These
      data provide direct evidence that E2A gene products can act as tumor suppressors.

PMID- 9927683
TI  - Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma
      protein-mediated G1 arrest after gamma-irradiation.
AB  - In mammalian cells, activation of certain checkpoint pathways as a result of
      exposure to genotoxic agents results in cell cycle arrest. The integrity of these
      arrest pathways is critical to the ability of the cell to repair mutations that
      otherwise might compromise viability or contribute to deregulation of cellular
      growth and proliferation. Here we examine the mechanism through which DNA
      damaging agents result in a G1 arrest that depends on the tumor suppressor p53
      and its transcriptional target p21. By using primary cell lines lacking specific
      cell cycle regulators, we demonstrate that this pathway functions through the
      growth suppressive properties of the retinoblastoma protein (pRB) tumor
      suppressor. Specifically, gamma-irradiation inhibits the phosphorylation of pRB
      at cyclin-dependent kinase 2-specific, but not cyclin-dependent kinase 4
      specific, sites in a p21-dependent manner. Most importantly, we show that pRB is
      a critical component of this DNA damage checkpoint. These data indicate that the
      p53 --> p21 checkpoint pathway uses the normal cell cycle regulatory machinery to
      induce the accumulation of the growth suppressive form of pRB and suggest that
      loss of pRB during the course of tumorigenesis disrupts the function of an
      important DNA damage checkpoint.

PMID- 9927684
TI  - Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD
      crystallin gene.
AB  - Cataracts are a significant public health problem. Here, we describe the genetic
      alteration responsible for a progressive form of cataract, segregating as an
      autosomal dominant trait in a three-generation pedigree. Unlike most autosomal
      dominant cataracts, these are not clinically apparent at birth but are initially
      observed in the first year or two of life. The opacification evolves relatively
      slowly, generally necessitating removal of the lens in childhood or early
      adolescence. A genome-wide search in our kindred revealed linkage at 2q33-35
      where the gamma-crystallin gene cluster resides. A single base alteration
      resulting in an Arg- 14 --> Cys (R14C) substitution in gammaD-crystallin was
      subsequently identified. Protein modeling suggests that the effect of this
      mutation is a subtle one, affecting the surface properties of the crystallin
      molecule rather than its tertiary structure, consistent with the fact that the
      patients' lenses are normal at birth. This is the first gene defect shown to be
      responsible for a noncongenital progressive cataract, and studying the defective
      protein should teach us more about the mechanisms underlying cataract formation.

PMID- 9927685
TI  - Generation of conditional mutants in higher eukaryotes by switching between the
      expression of two genes.
AB  - A regulatory system for the in-depth study of gene functions in higher eukaryotic
      cells has been developed. It is based on the tetracycline-controlled
      transactivators and reverse tTA, which were remodeled to discriminate efficiently
      between two different promoters. The system permits one to control reversibly the
      activity of two genes, or two alleles of a gene, in a mutually exclusive way, and
      also allows one to abrogate the activities of both. This dual regulatory circuit,
      which can be operated by a single effector substance such as doxycycline,
      overcomes limitations of conventional genetic approaches. The conditional mutants
      that can now be generated will be useful for the study of gene function in vitro
      and in vivo. In addition, the system may be of value for a variety of practical
      applications, including gene therapy.

PMID- 9927686
TI  - CD48-deficient mice have a pronounced defect in CD4(+) T cell activation.
AB  - We have generated mice deficient in the expression of the lymphocyte cell surface
      antigen CD48 (Blast-1, BCM1, sgp-60) by gene targeting in embryonic stem cells.
      Mice homozygous for the CD48 mutation (CD48(-/-) mice) are severely impaired in
      CD4(+) T cell activation. Proliferative responses to mitogens, anti-CD3 mAb, and
      alloantigen are all reduced. Experiments in which T cells and antigen-presenting
      cells from either wild-type or CD48(-/-) mice were cocultured reveal that CD48 is
      important on both T cells and antigen-presenting cells. The most dramatic
      impairment was observed in experiments in which highly purified T cells were
      stimulated through the T cell receptor in the presence of the phorbol ester,
      phorbol 12-myristate 13-acetate. The results of these experiments raise the
      possibility that CD48 plays a role in signaling through the T cell receptor.

PMID- 9927687
TI  - T cell antigen receptor-mediated activation of the Ras/mitogen-activated protein
      kinase pathway controls interleukin 4 receptor function and type-2 helper T cell
      differentiation.
AB  - The central role of type-2 helper T (Th2) cells in the development of allergic
      responses and immune responses against helminthic parasites is well documented.
      The differentiation of Th2 cells from naive T cells requires both the recognition
      of antigen by T cell antigen receptors (TCR) and the activation of downstream
      signal-transduction molecules of the interleukin 4 receptor (IL-4R) pathway,
      including Jak1, Jak3, and STAT6. Little is known, however, about how these two
      distinct pathways cooperate with each other to induce Th2 cells. Here, we use a T
      cell-specific H-Ras-dominant-negative transgenic mouse to show that TCR-mediated
      activation of the Ras/mitogen-activated protein kinase pathway alters IL-4R
      function and is required for Th2 cell differentiation. The enhancement of IL-4R
      signaling seems to be a consequence of both direct "crosstalk" with the TCR
      signaling pathway and increased protein expression of downstream signaling
      molecules of the IL-4R pathway. Therefore, successful Th2 differentiation depends
      on the effectiveness of the TCR-mediated activation of the Ras/mitogen-activated
      protein kinase pathway in modifying the IL-4R-mediated signaling pathway.

PMID- 9927688
TI  - Lack of infection in HIV-exposed individuals is associated with a strong CD8(+)
      cell noncytotoxic anti-HIV response.
AB  - Individuals repeatedly exposed to HIV, but who remain uninfected, form a
      population enriched for persons likely to have either natural or acquired
      resistance to the virus. We have studied four such exposed uninfected cohorts,
      representing 60 individuals, for evidence of protective immunity. This population
      included participants exposed to HIV through anal or vaginal receptive
      intercourse on multiple occasions over many years. We observed CD8(+)-cell
      noncytotoxic inhibition of HIV replication in acutely infected CD4(+) cells in
      the vast majority of individuals most recently exposed to the virus (within 1
      year). The levels of this CD8(+)-cell response were sufficient to inhibit the in
      vitro infection of the exposed subjects' peripheral blood mononuclear cells. We
      found no evidence of a significant role for CCR5 Delta32 mutation in this
      population, nor did CD4(+) cell susceptibility to infection or HIV-specific
      cytotoxic T-lymphocytes correlate with resistance to infection in the individuals
      tested. Therefore, the observed strong noncytotoxic CD8(+)-cell anti-HIV
      responses may be an antiviral immune activity contributing to the apparent
      protection from infection in these exposed uninfected individuals.

PMID- 9927689
TI  - Distinct dendritic cell subsets differentially regulate the class of immune
      response in vivo.
AB  - Dendritic cells (DCs) are unique in their ability to stimulate T cells and
      initiate adaptive immunity. Injection of mice with the cytokine Flt3-ligand (FL)
      dramatically expands mature lymphoid and myeloid-related DC subsets. In contrast,
      injection of a polyethylene glycol-modified form of granulocyte/macrophage colony
      stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset.
      These DC subsets differ in the cytokine profiles they induce in T cells in vivo.
      The lymphoid-related subset induces high levels of the Th1 cytokines interferon
      gamma and interleukin (IL)-2 but little or no Th2 cytokines. In contrast, the
      myeloid-related subset induces large amounts of the Th2 cytokines IL-4 and IL-10,
      in addition to interferon gamma and IL-2. FL- or GM-CSF-treated mice injected
      with soluble ovalbumin display dramatic increases in antigen-specific antibody
      titers, but the isotype profiles seem critically dependent on the cytokine used.
      Although FL treatment induces up to a 10, 000-fold increase in ovalbumin-specific
      IgG2a and a more modest increase in IgG1 titers, GM-CSF treatment favors a
      predominantly IgG1 response with little increase in IgG2a levels. These data
      suggest that distinct DC subsets have strikingly different influences on the type
      of immune response generated in vivo and may thus be targets for pharmacological
      intervention.

PMID- 9927690
TI  - Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and
      as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced
      apoptosis.
AB  - FIP-3 (14.7K interacting protein) was discovered during a search for cell
      proteins that could interact with an adenovirus protein (Ad E3-14.7K) that had
      been shown to prevent tumor necrosis factor (TNF)-alpha-induced cytolysis. FIP-3,
      which contains leucine zippers and a zinc finger domain, inhibits both basal and
      induced transcriptional activity of NF-kappaB and causes a late-appearing
      apoptosis with unique morphologic manifestations. Ad E3-14.7K can partially
      reverse apoptotic death induced by FIP-3. FIP-3 also was shown to bind to other
      cell proteins, RIP and NIK, which previously had been described as essential
      components of TNF-alpha-induced NF-kappaB activation. In addition, FIP-3
      inhibited activation of NF-kappaB induced by TNF-alpha, the TNFR-1 receptor, RIP,
      NIK, and IKKbeta, as well as basal levels of endogenous NF-kappaB in 293 cells.
      Because the activation of NF-kappaB has been shown to inhibit apoptosis, FIP-3
      appears both to activate a cell-death pathway and to inhibit an NF-kappaB
      dependent survival mechanism.

PMID- 9927691
TI  - The stretch-activation response may be critical to the proper functioning of the
      mammalian heart.
AB  - The "stretch-activation" response is essential to the generation of the
      oscillatory power required for the beating of insect wings. It has been
      conjectured but not previously shown that a stretch-activation response
      contributes to the performance of a beating heart. Here, we generated transgenic
      mice that express a human mutant myosin essential light chain derived from a
      family with an inherited cardiac hypertrophy. These mice faithfully replicate the
      cardiac disease of the patients with this mutant allele. They provide the
      opportunity to study the stretch-activation response before the hearts are
      distorted by the hypertrophic process. Studies disclose a mismatch between the
      physiologic heart rate and resonant frequency of the cardiac papillary muscles
      expressing the mutant essential light chain. This discordance reduces oscillatory
      power at frequencies that correspond to physiologic heart-rates and is followed
      by subsequent hypertrophy. It appears, therefore, that the stretch-activation
      response, first described in insect flight muscle, may play a role in the
      mammalian heart, and its further study may suggest a new way to modulate human
      cardiac function.

PMID- 9927692
TI  - Defective collagen crosslinking in bone, but not in ligament or cartilage, in
      Bruck syndrome: indications for a bone-specific telopeptide lysyl hydroxylase on
      chromosome 17.
AB  - Bruck syndrome is characterized by the presence of osteoporosis, joint
      contractures, fragile bones, and short stature. We report that lysine residues
      within the telopeptides of collagen type I in bone are underhydroxylated, leading
      to aberrant crosslinking, but that the lysine residues in the triple helix are
      normally modified. In contrast to bone, cartilage and ligament show unaltered
      telopeptide hydroxylation as evidenced by normal patterns of crosslinking. The
      results provide compelling evidence that collagen crosslinking is regulated
      primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine
      residues and not those destined for the helical portion of the molecule. This new
      family of enzymes appears to provide the primary regulation for controlling the
      different pathways of collagen crosslinking and explains why crosslink patterns
      are tissue specific and not related to a genetic collagen type. A genome screen
      identified only a single region on chromosome 17p12 where all affected sibs
      shared a cluster of haplotypes identical by descent; this might be the BS (Bruck
      syndrome) locus and consequently the region where bone telopeptidyl lysyl
      hydroxylase is located. Further knowledge of this enzyme has important
      implications for conditions where aberrant expression of telopeptide lysyl
      hydroxylase occurs, such as fibrosis and scar formation.

PMID- 9927693
TI  - Enhancing versus suppressive effects of stress hormones on skin immune function.
AB  - Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated
      immune responses that, depending on the antigen, mediate beneficial (e.g.,
      resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis
      and autoimmunity) aspects of immune function. Contrary to the idea that stress
      suppresses immunity, we have reported that short-duration stressors significantly
      enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin
      may mediate this immunoenhancement. Here, we identify the hormonal mediators of a
      stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the
      glucocorticoid and epinephrine stress response, eliminated the stress-induced
      enhancement of skin DTH. Low-dose corticosterone or epinephrine administration
      significantly enhanced skin DTH and produced a significant increase in the number
      of T cells in lymph nodes draining the site of the DTH reaction. In contrast,
      high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone
      administration significantly suppressed skin DTH. These results suggest a role
      for adrenal stress hormones as endogenous immunoenhancing agents. These results
      also show that hormones released during an acute stress response may help prepare
      the immune system for potential challenges (e.g., wounding or infection) for
      which stress perception by the brain may serve as an early warning signal.

PMID- 9927694
TI  - Gene therapy to promote thromboresistance: local overexpression of tissue
      plasminogen activator to prevent arterial thrombosis in an in vivo rabbit model.
AB  - Tissue-type plasminogen activator (tPA) catalyzes the rate-limiting initial step
      in the fibrinolytic cascade. Systemic infusion of tPA has become the standard of
      care for acute myocardial infarction. However, even the relatively short-duration
      protocols currently employed have encountered significant hemorrhagic
      complications, as well as complications from rebound thrombosis. Gene therapy
      offers a method of local high-level tPA expression over a prolonged time period
      to avoid both systemic hemorrhage and local rebound thrombosis. To examine the
      impact of local tPA overexpression, an adenoviral vector expressing tPA was
      created. The construct was characterized functionally in vitro, and the function
      of the vector was confirmed in vivo by delivery to the rabbit common femoral
      artery. Systemic coagulation parameters were not perturbed at any of the doses
      examined. The impact of local overexpression of tPA on in vivo thrombus formation
      was examined subsequently in a stasis/injury model of arterial thrombosis. The
      construct effectively prevented arterial thrombosis in treated animals, whereas
      viral and nonviral controls typically developed occluding thrombi. This construct
      thus offers a viable technique for promoting a locally thromboresistant small
      caliber artery.

PMID- 9927695
TI  - Identification of a vibrio cholerae RTX toxin gene cluster that is tightly linked
      to the cholera toxin prophage.
AB  - We identify and characterize a gene cluster in El Tor Vibrio cholerae that
      encodes a cytotoxic activity for HEp-2 cells in vitro. This gene cluster contains
      four genes and is physically linked to the cholera toxin (CTX) element in the V.
      cholerae genome. We demonstrate by using insertional mutagenesis that this gene
      cluster is required for the cytotoxic activity. The toxin, RtxA, resembles
      members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich
      repeated motif. Like other RTX toxins, its activity depends on an activator,
      RtxC, and an associated ABC transporter system, RtxB and RtxD. In V. cholerae
      strains of the classical biotype, a deletion within the gene cluster removes rtxC
      and eliminates cytotoxic activity. Other strains, including those of the current
      cholera pandemic, contain a functional gene cluster and display cytotoxic
      activity. Thus, the RTX gene cluster in El Tor O1 and O139 strains might have
      contributed significantly to their emergence. Furthermore, the RTX toxin of V.
      cholerae may be associated with residual adverse properties displayed by certain
      live, attenuated cholera vaccines.

PMID- 9927696
TI  - Variation in expression of the Haemophilus influenzae HMW adhesins: a prokaryotic
      system reminiscent of eukaryotes.
AB  - Expression of a number of eukaryotic genes is regulated by long stretches of
      tandem repeats located within the 5' untranslated region of the particular gene.
      In this study, we describe a regulatory system in Haemophilus influenzae with
      striking similarities to those found in eukaryotes. We show that expression of
      the HMW1 and HMW2 adhesins varies based on the number of 7-bp tandem repeats in
      the hmw1A and hmw2A promoters. The repeats lie between two separate transcription
      initiation sites and exert a repressive effect, such that increases in repeat
      number result in step-wise decreases in levels of specific mRNA and protein
      production and vice versa. The range of expression of HMW1 and HMW2 varies
      between very weak and very strong, with a series of gradations in between.
      Variation in the number of repeats in the hmw1A and hmw2A promoters occurs in
      individual colonies passaged in vitro, in an animal model of infection, and
      during natural infection in humans. This system of regulation is unique in
      prokaryotes and likely enhances the pathogenicity of the organism by increasing
      adaptive potential.

PMID- 9927697
TI  - The role of presynaptic activity in monocular deprivation: comparison of
      homosynaptic and heterosynaptic mechanisms.
AB  - Although investigations in computational neuroscience have been extensive, the
      opportunity (that has made such a marked difference in physical sciences) to test
      detailed and subtle quantitative consequences of a theory against experimental
      results is rare. In this paper, we outline a testable consequence of two
      contrasting theories of synaptic plasticity applied to the disconnection in
      visual cortex of the closed eye in monocular deprivation. This disconnection is
      sometimes thought to be the consequence of a process that stems from a
      competition of inputs for a limited resource such as neurotrophin. Such a process
      leads to what we call spatial competition, or heterosynaptic synaptic
      modification. A contrasting view-exemplified by the Bienenstock, Cooper, and
      Munro (BCM) theory-is that patterns of input activity compete in the temporal
      domain. This temporal competition is homosynaptic and does not require a
      conserved resource. The two mechanisms, homosynaptic and heterosynaptic, are the
      distinguishing characteristics of two general classes of learning rules we
      explore by using a realistic environment composed of natural scenes. These
      alternative views lead to opposite dependence on the level of presynaptic
      activity of the rate of disconnection of the closed eye in monocular deprivation.
      This strong and testable consequence sets the stage for a critical distinguishing
      experiment. This experiment has been done and supports the second view. These
      results have important implications for the processes of learning and memory
      storage in neocortex.

PMID- 9927698
TI  - Molecular and functional remodeling of electrogenic membrane of hypothalamic
      neurons in response to changes in their input.
AB  - Neurons respond to stimuli by integrating generator and synaptic potentials and
      generating action potentials. However, whether the underlying electrogenic
      machinery within neurons itself changes, in response to alterations in input, is
      not known. To determine whether there are changes in Na+ channel expression and
      function within neurons in response to altered input, we exposed magnocellular
      neurosecretory cells (MNCs) in the rat supraoptic nucleus to different osmotic
      milieus by salt-loading and studied Na+ channel mRNA and protein, and Na+
      currents, in these cells. In situ hybridization demonstrated significantly
      increased mRNA levels for alpha-II, Na6, beta1 and beta2 Na+ channel subunits,
      and immunohistochemistry/immunoblotting showed increased Na+ channel protein
      after salt-loading. Using patch-clamp recordings to examine the deployment of
      functional Na+ channels in the membranes of MNCs, we observed an increase in the
      amplitude of the transient Na+ current after salt-loading and an even greater
      increase in amplitude and density of the persistent Na+ current evoked at
      subthreshold potentials by slow ramp depolarizations. These results demonstrate
      that MNCs respond to salt-loading by selectively synthesizing additional,
      functional Na+ channel subtypes whose deployment in the membrane changes its
      electrogenic properties. Thus, neurons may respond to changes in their input not
      only by producing different patterns of electrical activity, but also by
      remodeling the electrogenic machinery that underlies this activity.

PMID- 9927699
TI  - A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP
      exchange factor msec7-1.
AB  - ADP ribosylation factors (ARFs) represent a family of small monomeric G proteins
      that switch from an inactive, GDP-bound state to an active, GTP-bound state. One
      member of this family, ARF6, translocates on activation from intracellular
      compartments to the plasma membrane and has been implicated in regulated
      exocytosis in neuroendocrine cells. Because GDP release in vivo is rather slow,
      ARF activation is facilitated by specific guanine nucleotide exchange factors
      like cytohesin-1 or ARNO. Here we show that msec7-1, a rat homologue of cytohesin
      1, translocates ARF6 to the plasma membrane in living cells. Overexpression of
      msec7-1 leads to an increase in basal synaptic transmission at the Xenopus
      neuromuscular junction. msec7-1-containing synapses have a 5-fold higher
      frequency of spontaneous synaptic currents than control synapses. On stimulation,
      the amplitudes of the resulting evoked postsynaptic currents of msec7-1
      overexpressing neurons are increased as well. However, further stimulation leads
      to a decline in amplitudes approaching the values of control synapses. This
      transient effect on amplitude is strongly reduced on overexpression of msec7
      1E157K, a mutant incapable of translocating ARFs. Our results provide evidence
      that small G proteins of the ARF family and activating factors like msec7-1 play
      an important role in synaptic transmission, most likely by making more vesicles
      available for fusion at the plasma membrane.

PMID- 9927700
TI  - Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses.
AB  - At the synapse, presynaptic membranes specialized for vesicular traffic are
      linked to postsynaptic membranes specialized for signal transduction. The
      mechanisms that connect pre- and postsynaptic membranes into synaptic junctions
      are unknown. Neuroligins and beta-neurexins are neuronal cell-surface proteins
      that bind to each other and form asymmetric intercellular junctions. To test
      whether the neuroligin/beta-neurexin junction is related to synapses, we
      generated and characterized monoclonal antibodies to neuroligin 1. With these
      antibodies, we show that neuroligin 1 is synaptic. The neuronal localization,
      subcellular distribution, and developmental expression of neuroligin 1 are
      similar to those of the postsynaptic marker proteins PSD-95 and NMDA-R1 receptor.
      Quantitative immunogold electron microscopy demonstrated that neuroligin 1 is
      clustered in synaptic clefts and postsynaptic densities. Double
      immunofluorescence labeling revealed that neuroligin 1 colocalizes with
      glutamatergic but not gamma-aminobutyric acid (GABA)ergic synapses. Thus
      neuroligin 1 is a synaptic cell-adhesion molecule that is enriched in
      postsynaptic densities where it may recruit receptors, channels, and signal
      transduction molecules to synaptic sites of cell adhesion. In addition, the
      neuroligin/beta-neurexin junction may be involved in the specification of
      excitatory synapses.

PMID- 9927701
TI  - Spatiotemporal activity patterns of rat cortical neurons predict responses in a
      conditioned task.
AB  - Precise and repeated spike-train timings within and across neurons define
      spatiotemporal patterns of activity. Although the existence of these patterns in
      the brain is well established in several species, there has been no direct
      evidence of their influence on behavioral output. To address this question, up to
      15 neurons were recorded simultaneously in the auditory cortex of freely moving
      rats while animals waited for acoustic cues in a Go/NoGo task. A total of 235
      significant patterns were detected during this interval from an analysis of 13 hr
      of recording involving over 1 million spikes. Of particular interest were 129
      (55%) patterns that were significantly associated with the type of response the
      animal made later, independent of whether the response was that prompted by the
      cue because the response occurred later and the cue was chosen randomly. Of these
      behavior-predicting patterns, half (59/129) were associated with an enhanced
      tendency to go in response to the stimulus, and for 11 patterns of this subset,
      trials including the pattern were followed by significantly faster reaction time
      than those lacking the pattern. The remaining behavior-predicting patterns were
      associated with an enhanced NoGo tendency. Overall mean discharge rates did not
      vary across trials. Hence, these data demonstrate that particular spatiotemporal
      patterns predict future behavioral responses. Such presignal activity could form
      templates for extracting specific sensory information, motor programs
      prespecifying preference for a particular act, and/or some intermediate,
      associative brain process.

PMID- 9927702
TI  - Neurotrophins regulate agrin-induced postsynaptic differentiation.
AB  - The precise orchestration of synaptic differentiation is critical for efficient
      information exchange in the nervous system. The nerve-muscle synapse forms in
      response to agrin, which is secreted from the motor nerve terminal and induces
      the clustering of acetylcholine receptors (AChRs) and other elements of the
      postsynaptic apparatus on the subjacent muscle cell surface. In view of the
      highly restricted spatial localization and the plasticity of neuromuscular
      junctions, it seems likely that synapse formation and maintenance are regulated
      by additional, as-yet-unidentified factors. Here, we tested whether neurotrophins
      modulate the agrin-induced differentiation of postsynaptic specializations. We
      show that both brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4)
      inhibit agrin-induced AChR clustering on cultured myotubes. Nerve growth factor
      and NT-3 are without effect. Muscle cells express full-length TrkB, the cognate
      receptor for BDNF and NT-4. Direct activation of this receptor by anti-TrkB
      antibodies mimicked the BDNF/NT-4 inhibition of agrin-induced AChR clustering.
      This BDNF/NT-4 inhibition is likely to be an intrinsic mechanism for regulating
      AChR clustering, because neutralization of endogenous TrkB ligands resulted in
      elevated levels of AChR clustering even in the absence of added agrin. Finally,
      high concentrations of agrin can occlude the BDNF/NT-4 inhibition of AChR
      clustering. These results indicate that an interplay between agrin and
      neurotrophins can regulate the formation of postsynaptic specializations. They
      also suggest a mechanism for the suppression of postsynaptic specializations at
      nonjunctional regions.

PMID- 9927703
TI  - Glutamate and gamma-aminobutyric acid mediate a heterosynaptic depression at
      mossy fiber synapses in the hippocampus.
AB  - Mossy fiber synapses form the major excitatory input into the autoassociative
      network of pyramidal cells in the CA3 area of the hippocampus. Here we
      demonstrate that at the mossy fiber synapses, glutamate and gamma-aminobutyric
      acid (GABA) act as autaptic and heterosynaptic presynaptic inhibitory
      transmitters through metabotropic glutamate receptors (mGluRs) and GABAB
      receptors, respectively. Both GABAB receptors and mGluRs are activated through
      spillover from adjacent synapses. We demonstrate that glutamate spillover caused
      by brief tetanic activation of mossy fiber terminals remains intact at
      physiological temperatures. The activation of GABAB receptors increased the
      threshold for mossy fiber long-term potentiation (LTP), whereas activation of
      mGluRs did not have such an effect. We speculate that this heterosynaptic
      depression provides the mossy fiber synapses with a mechanism to efficiently
      shape input patterns into CA3, increasing the sparseness of the mossy fiber
      signal and enhancing the capacity and performance of the CA3 associative network.
      The increase in LTP threshold through activation of presynaptic inhibitory
      receptors imparts a piesynoptic associative nature to mossy fiber LTP.

PMID- 9927704
TI  - Isometric contraction induces the Ca2+-independent activation of the endothelial
      nitric oxide synthase.
AB  - Shear stress and tyrosine phosphatase inhibitors have been shown to activate the
      endothelial NO synthase (eNOS) in a Ca2+/calmodulin-independent manner. We report
      here that isometric contraction of rabbit aorta activates eNOS by a
      pharmacologically identical pathway. Endothelium-intact aortic rings were
      precontracted under isometric conditions up to 60% of the maximal phenylephrine
      induced tone. The NO synthase inhibitor NGnitro-L-arginine (L-NA) and the soluble
      guanylyl cyclase inhibitor NS 2028 induced an additional contraction, the
      amplitude of which depended on the level of precontraction. The maximal
      production of NO by isometrically contracted aortic rings (as estimated by the
      increase in cGMP in detector smooth muscle cells in a superfusion bioassay) was
      observed during the initial phase of isometric contraction and was greater than
      that detected following the application of acetylcholine. The supplementary L-NA
      induced increase in vascular tone was inhibited by the nonselective kinase
      inhibitor staurosporine and the tyrosine kinase inhibitors erbstatin A and
      herbimycin A. Another tyrosine kinase inhibitor, genistein, the calmodulin
      antagonist calmidazolium, and the selective protein kinase C inhibitor, Ro 31
      8220, had no effect. Coincident with the enhanced NO formation during isometric
      contraction was an increase in the tyrosine phosphorylation of endothelial
      proteins, which also correlated with the level of precontraction. Thus, isometric
      contraction activates eNOS via a Ca2+-independent, tyrosine kinase inhibitor
      sensitive pathway and, like shear stress, seems to be an independent determinant
      of mechanically induced NO formation.

PMID- 9927706
TI  - Unusual carotenoid composition and a new type of xanthophyll cycle in plants.
AB  - The capture of photons by the photosynthetic apparatus is the first step in
      photosynthesis in all autotrophic higher plants. This light capture is dominated
      by pigment-containing proteins known as light-harvesting complexes (LHCs). The
      xanthophyll-carotenoid complement of these LHCs (neoxanthin, violaxanthin, and
      lutein) is highly conserved, with no deletions and few, uncommon additions. We
      report that neoxanthin, considered an integral component of LHCs, is
      stoichiometrically replaced by lutein-5,6-epoxide in the parasitic angiosperm
      Cuscuta reflexa, without compromising the structural integrity of the LHCs.
      Lutein-5,6-epoxide differs from neoxanthin in that it is involved in a light
      driven deepoxidation cycle similar to the deepoxidation of violaxanthin in the
      xanthophyll cycle, which is implicated in protection against photodamage. The
      absence of neoxanthin and its replacement by lutein-5,6-epoxide changes our
      understanding of the structure-function relationship in LHCs, has implications
      for biosynthetic pathways involving neoxanthin (such as the plant hormone
      abscisic acid), and identifies one of the early steps associated with the
      evolution of heterotrophy from autotrophy in plants.

PMID- 9927705
TI  - Role of mitochondrial lactate dehydrogenase and lactate oxidation in the
      intracellular lactate shuttle.
AB  - To evaluate the potential role of mitochondrial lactate dehydrogenase (LDH) in
      tissue lactate clearance and oxidation in vivo, isolated rat liver, cardiac, and
      skeletal muscle mitochondria were incubated with lactate, pyruvate, glutamate,
      and succinate. As well, alpha-cyano-4-hydroxycinnamate (CINN), a known
      monocarboxylate transport inhibitor, and oxamate, a known LDH inhibitor were
      used. Mitochondria readily oxidized pyruvate and lactate, with similar state 3
      and 4 respiratory rates, respiratory control (state 3/state 4), and ADP/O ratios.
      With lactate or pyruvate as substrates, alpha-cyano-4-hydroxycinnamate blocked
      the respiratory response to added ADP, but the block was bypassed by addition of
      glutamate (complex I-linked) and succinate (complex II-linked) substrates.
      Oxamate increased pyruvate (approximately 10-40%), but blocked lactate oxidation.
      Gel electrophoresis and electron microscopy indicated LDH isoenzyme distribution
      patterns to display tissue specificity, but the LDH isoenzyme patterns in
      isolated mitochondria were distinct from those in surrounding cell compartments.
      In heart, LDH-1 (H4) was concentrated in mitochondria whereas LDH-5 (M4) was
      present in both mitochondria and surrounding cytosol and organelles. LDH-5
      predominated in liver but was more abundant in mitochondria than elsewhere.
      Because lactate exceeds cytosolic pyruvate concentration by an order of
      magnitude, we conclude that lactate is the predominant monocarboxylate oxidized
      by mitochondria in vivo. Mammalian liver and striated muscle mitochondria can
      oxidize exogenous lactate because of an internal LDH pool that facilitates
      lactate oxidation.

PMID- 9927707
TI  - ARG1 (altered response to gravity) encodes a DnaJ-like protein that potentially
      interacts with the cytoskeleton.
AB  - Gravitropism allows plant organs to direct their growth at a specific angle from
      the gravity vector, promoting upward growth for shoots and downward growth for
      roots. Little is known about the mechanisms underlying gravitropic signal
      transduction. We found that mutations in the ARG1 locus of Arabidopsis thaliana
      alter root and hypocotyl gravitropism without affecting phototropism, root growth
      responses to phytohormones or inhibitors of auxin transport, or starch
      accumulation. The positional cloning of ARG1 revealed a DnaJ-like protein
      containing a coiled-coil region homologous to coiled coils found in cytoskeleton
      interacting proteins. These data suggest that ARG1 participates in a gravity
      signaling process involving the cytoskeleton. A combination of Northern blot
      studies and analysis of ARG1-GUS fusion-reporter expression in transgenic plants
      demonstrated that ARG1 is expressed in all organs. Ubiquitous ARG1 expression in
      Arabidopsis and the identification of an ortholog in Caenorhabditis elegans
      suggest that ARG1 is involved in other essential processes.

PMID- 9927708
TI  - Antisense-mediated depletion of a potato lipoxygenase reduces wound induction of
      proteinase inhibitors and increases weight gain of insect pests.
AB  - De novo jasmonic acid (JA) synthesis is required for wound-induced expression of
      proteinase inhibitors and other defense genes in potato and tomato. The first
      step in JA biosynthesis involves lipoxygenase (LOX) introducing molecular oxygen
      at the C-13 position of linolenic acid. We previously have shown that, in potato,
      at least two gene families code for 13-LOX proteins. We have now produced
      transgenic potato plants devoid of one specific 13-LOX isoform (LOX-H3) through
      antisense-mediated depletion of its mRNA. LOX-H3 depletion largely abolishes
      accumulation of proteinase inhibitors on wounding, indicating that this specific
      LOX plays an instrumental role in the regulation of wound-induced gene
      expression. As a consequence, weight gain of Colorado potato beetles fed on
      antisense plants is significantly larger than those fed on wild-type plants. The
      poorer performance of LOX-H3-deficient plants toward herbivory is more evident
      with a polyphagous insect; larvae of beet armyworm reared on the antisense lines
      have up to 57% higher weight than those fed on nontransformed plants. LOX-H3 thus
      appears to regulate gene activation in response to pest attack, and this
      inducible response is likely to be a major determinant for reducing performance
      of nonspecialized herbivores. However, the regulatory role of LOX-H3 is not
      caused by its involvement in the wound-induced increase of JA, as wild-type and
      LOX-H3 deficient plants have similar jasmonate levels after wounding. LOX-H3
      deficient plants have higher tuber yields. The apparent effect of suppressing the
      inducible defensive response on plant vigor suggests that it may pose a penalty
      in plant fitness under nonstress situations.

PMID- 9927709
TI  - The relationship between the volume of antimicrobial consumption in human
      communities and the frequency of resistance.
AB  - The threat to human health posed by antibiotic resistance is of growing concern.
      Many commensal and pathogenic organisms have developed resistance to well
      established and newer antibiotics. The major selection pressure driving changes
      in the frequency of antibiotic resistance is the volume of drug use. However,
      establishing a quantitative relationship between the frequency of resistance and
      volume of drug use has proved difficult. Using population genetic methods and
      epidemiological observations, we report an analysis of the influence of the
      selective pressure imposed by the volume of drug use on temporal changes in
      resistance. Analytical expressions are derived to delineate key relationships
      between resistance and drug consumption. The analyses indicate that the time
      scale for emergence of resistance under a constant selective pressure is
      typically much shorter than the decay time after cessation or decline in the
      volume of drug use and that significant reductions in resistance require equally
      significant reductions in drug consumption. These results highlight the need for
      early intervention once resistance is detected.

PMID- 9927710
TI  - Skeletal and dental morphology supports diphyletic origin of baboons and
      mandrills.
AB  - Numerous biomolecular studies from the past 20 years have indicated that the
      large African monkeys Papio, Theropithecus, and Mandrillus have a diphyletic
      relationship with different species groups of mangabeys. According to the results
      of these studies, mandrills and drills (Mandrillus) are most closely related to
      the torquatus-galeritus group of mangabeys placed in the genus Cercocebus,
      whereas baboons (Papio) and geladas (Theropithecus) are most closely related to
      the albigena-aterrimus mangabeys, now commonly placed in the genus Lophocebus.
      However, there has been very little morphological evidence linking mandrills on
      the one hand and baboons and geladas on the other with different groups of
      mangabeys. In a study of mangabey locomotion and skeletal anatomy, we have
      identified features of the postcranial skeleton and the dentition that support
      the molecular phylogeny and clearly link mandrills with Cercocebus and Papio with
      Lophocebus. Moreover, the features linking Cercocebus and Mandrillus accord with
      ecological studies of these species indicating that these two genera are a
      cryptic clade characterized by unique adaptations for gleaning insects, hard
      nuts, and seeds from the forest floor.

PMID- 9927711
TI  - Empirical estimation of the reliability of ribosomal RNA alignments.
AB  - MOTIVATION: The automatic alignment of rRNA sequences can reproduce manual expert
      alignments with high, but not perfect, fidelity. We examine the use of empirical
      methods for the identification of regions of an alignment of a new sequence with
      an existing large alignment which can confidently be predicted to be correctly
      aligned. RESULTS: We show how to use a simple jack-knife procedure to derive an
      estimate of the reliability that is to be expected at each position of a large
      alignment of eukaryotic rRNA sequences. These reliabilities are then improved
      using measures that are specific to the input sequence. Regions where the
      sequence-specific reliability method performs particularly well are identified
      and seen to correspond with elements in the structure of the rRNA molecules that
      vary between species in the alignment. We also compare these reliability measures
      to an algorithmic alignment stability measure. AVAILABILITY: The software is
      available free of charge by sending an e-mail message to emmet@chah.ucc.ie.
      CONTACT: emmet@chah.ucc.ie

PMID- 9927712
TI  - SALSA: improved protein database searching by a new algorithm for assembly of
      sequence fragments into gapped alignments.
AB  - MOTIVATION: Optimal sequence alignment based on the Smith-Waterman algorithm is
      usually too computationally demanding to be practical for searching large
      sequence databases. Heuristic programs like FASTA and BLAST have been developed
      which run much faster, but at the expense of sensitivity. RESULTS: In an effort
      to approximate the sensitivity of an optimal alignment algorithm, a new algorithm
      has been devised for the computation of a gapped alignment of two sequences.
      After scanning for high-scoring words and extensions of these to form fragments
      of similarity, the algorithm uses dynamic programming to build an accurate
      alignment based on the fragments initially identified. The algorithm has been
      implemented in a program called SALSA and the performance has been evaluated on a
      set of test sequences. The sensitivity was found to be close to the Smith
      Waterman algorithm, while the speed was similar to FASTA (ktup = 2).
      AVAILABILITY: Searches can be performed from the SALSA homepage at
      http://dna.uio.no/salsa/ using a wide range of databases. Source code and
      precompiled executables are also available. CONTACT:
      torbjorn.rognes@labmed.uio.no

PMID- 9927713
TI  - Hidden Markov models for detecting remote protein homologies.
AB  - MOTIVATION: A new hidden Markov model method (SAM-T98) for finding remote
      homologs of protein sequences is described and evaluated. The method begins with
      a single target sequence and iteratively builds a hidden Markov model (HMM) from
      the sequence and homologs found using the HMM for database search. SAM-T98 is
      also used to construct model libraries automatically from sequences in structural
      databases. METHODS: We evaluate the SAM-T98 method with four datasets. Three of
      the test sets are fold-recognition tests, where the correct answers are
      determined by structural similarity. The fourth uses a curated database. The
      method is compared against WU-BLASTP and against DOUBLE-BLAST, a two-step method
      similar to ISS, but using BLAST instead of FASTA. RESULTS: SAM-T98 had the fewest
      errors in all tests-dramatically so for the fold-recognition tests. At the
      minimum-error point on the SCOP (Structural Classification of Proteins)-domains
      test, SAM-T98 got 880 true positives and 68 false positives, DOUBLE-BLAST got 533
      true positives with 71 false positives, and WU-BLASTP got 353 true positives with
      24 false positives. The method is optimized to recognize superfamilies, and would
      require parameter adjustment to be used to find family or fold relationships. One
      key to the performance of the HMM method is a new score-normalization technique
      that compares the score to the score with a reversed model rather than to a
      uniform null model. AVAILABILITY: A World Wide Web server, as well as information
      on obtaining the Sequence Alignment and Modeling (SAM) software suite, can be
      found at http://www.cse.ucsc.edu/research/compbi o/ CONTACT:
      karplus@cse.ucsc.edu; http://www.cse.ucsc.edu/karplus

PMID- 9927714
TI  - A new criterion to classify globular proteins based on their secondary structure
      contents.
AB  - MOTIVATION: With the enlargement of protein structure databases, it is hoped that
      a method to classify proteins automatically will be developed. Although the
      classification criterion proposed by Nakashima et al. ( J. Biochem., 1986, 99,
      153-162) was widely used in the literature, it leads to some inconsistencies with
      the classification databases currently available in the class assignment of
      protein structures. To improve their work, a new classification criterion is
      proposed relying on statistical analysis of the secondary structure contents of
      more than 200 proteins with well-known structural classes. The Fisher linear
      discriminant algorithm is used to derive the new classification criterion.
      RESULTS: Three cross-validation tests are performed to evaluate the new
      criterion. In the jackknife test, of the 210 proteins used to derive the
      criterion, 206 are correctly classified with an accuracy of 98.10%. Of the 16
      proteins of purely intermediate structure (i.e. structures lying near borderlines
      between two classes) in the first test set, 15 are correctly classified with an
      accuracy of 93.75%. For the second test set which consists of 200 proteins
      selected randomly from SCOP, a testing accuracy of 94.00% is obtained. For
      comparison, the criterion of Nakashima et al. is also used to classify the 210,
      16 and 200 proteins, respectively. Consequently, accuracies of 94.76%, 62.50% and
      91.50% are obtained, respectively. On average, the accuracy of the new
      classification criterion is 4% higher than that of Nakashima et al. AVAILABILITY:
      The program is available on request from the first author. CONTACT:
      ctzhang@tju.edu.cn

PMID- 9927715
TI  - VHMPT: a graphical viewer and editor for helical membrane protein topologies.
AB  - MOTIVATION: Lacking structures resolved at atomic resolution, the great majority
      of membrane proteins have typically been depicted in a schematic two-dimensional
      (2D) topology consisting of putative transmembrane domains predicted from
      hydropathy plots. As more and more sequences of membrane proteins become
      available from genome projects, there is a need to automate the process of
      generating the schematic topology while allowing important information, such as
      the individual amino acid and the extent to which it is conserved in evolution,
      to be conveniently inspected. We addressed this need by developing a program
      called VHMPT. RESULTS: VHMPT (a graphical V iewer and editor for H elical line M
      embrane P rotein T opologies) can automatically generate a schematic 2D topology
      for a protein with transmembrane helices. Through an interactive graphical
      interface, VHMPT allows users to modify the layout of the generated topology,
      label specific amino acid or amino acid groups, and annotate with arrows and
      texts. Given a multiple sequence alignment file, VHMPT can also color code a
      normalized conservation score for each amino acid on the generated topology,
      allowing ready visual recognition of highly conserved (or variable) topological
      regions. VHMPT is written in Tcl/Tk and can run on platforms that have installed
      the Tcl/Tk interpreter. AVAILABILITY: The source code and a user manual for VHMPT
      are available for download at http://www. ibms.sinica.edu.tw/mjhwang/vhmpt.
      CONTACT: mjhwang@mail.ibms.sinica.edu.tw

PMID- 9927716
TI  - Non-linear optimization of biochemical pathways: applications to metabolic
      engineering and parameter estimation.
AB  - MOTIVATION: The simulation of biochemical kinetic systems is a powerful approach
      that can be used for: (i) checking the consistency of a postulated model with a
      set of experimental measurements, (ii) answering 'what if?' questions and (iii)
      exploring possible behaviours of a model. Here we describe a generic approach to
      combine numerical optimization methods with biochemical kinetic simulations,
      which is suitable for use in the rational design of improved metabolic pathways
      with industrial significance (metabolic engineering) and for solving the inverse
      problem of metabolic pathways, i.e. the estimation of parameters from measured
      variables. RESULTS: We discuss the suitability of various optimization methods,
      focusing especially on their ability or otherwise to find global optima. We
      recommend that a suite of diverse optimization methods should be available in
      simulation software as no single one performs best for all problems. We describe
      how we have implemented such a simulation-optimization strategy in the
      biochemical kinetics simulator Gepasi and present examples of its application.
      AVAILABILITY: The new version of Gepasi (3.20), incorporating the methodology
      described here, is available on the Internet at
      http://gepasi.dbs.aber.ac.uk/softw/Gepasi. html. CONTACT: prm@aber.ac.uk

PMID- 9927717
TI  - GeneDn: for high-level expression design of heterologous genes in a prokaryotic
      system.
AB  - RESULTS: Based on the mathematical model of high-level expression of heterologous
      genes in prokaryotic vector pBV220, we developed a program GeneDn for high-level
      expression design of natural and synthetic genes. AVAILIBILITY: The program is
      written in Turbo Pascal 7.0. The source code and related material are available
      upon request. CONTACT: wujj@nic.bmi.ac.cn

PMID- 9927718
TI  - HIV-1 genotypic resistance: automated sequence analysis and interpretation.
AB  - We present here GRANT ( G enotypic R esistance An alysis T ool), a program that
      automatically detects resistance-related mutations in HIV-1 protein sequences,
      and comments on the degree of resistance conferred when possible. This program is
      easily user-customizable, allowing immediate updates as new resistance mutations
      are discovered, or use with an organism other than HIV. AVAILABILITY: The package
      is available free of charge over the internet, either directly from the authors,
      or by anonymous ftp (ftp. infobiogen.fr/pub/logiciels/mac/biology or windows as
      appropriate). Versions exist for PPC and 68K Apple Macintosh running MacOS 7.5 or
      higher. Microsoft Excel 5.0 is required for quality output. A PC version is in
      progress. CONTACT: goujon@infobiogen.fr

PMID- 9927719
TI  - BioABACUS: a database of abbreviations and acronyms in biotechnology and computer
      science.
AB  - BioABACUS (Biotechnology AB breviation and A cronym U ncovering Service) a new,
      searchable, cross-referenced, database of abbreviations and acronyms in
      biotechnology and computer science is described. AVAILABILITY: BioABACUS is
      accessible over the World Wide Web at
      http://www.nmsu.edu/molbio/bioABACUShome.htm. CONTACT:
      mrimer@nmsu.edu,moconnel@nmsu.edu

PMID- 9927720
TI  - BEAUTY-X: enhanced BLAST searches for DNA queries.
AB  - BEAUTY (BLAST Enhanced Alignment Utility) is an enhanced version of the BLAST
      database search tool that facilitates identification of the functions of matched
      sequences. Three recent improvements to the BEAUTY program described here make
      the enhanced output (1) available for DNA queries, (2) available for searches of
      any protein database, and (3) more up-to-date, with periodic updates of the
      domain information. AVAILABILITY: BEAUTY searches of the NCBI and EMBL non
      redundant protein sequence databases are available from the BCM Search Launcher
      Web pages (http://gc.bcm.tmc. edu:8088/search-launcher/launcher.html). BEAUTY
      Post-Processing of submitted search results is available using the BCM Search
      Launcher Batch Client (version 2.6) (ftp://gc.bcm.tmc. edu/pub/software/search
      launcher/). SUPPLEMENTARY INFORMATION: Example figures are available at
      http://dot.bcm.tmc. edu:9331/papers/beautypp.html CONTACT:
      (kworley,culpep)@bcm.tmc.edu

PMID- 9927721
TI  - JPred: a consensus secondary structure prediction server.
AB  - An interactive protein secondary structure prediction Internet server is
      presented. The server allows a single sequence or multiple alignment to be
      submitted, and returns predictions from six secondary structure prediction
      algorithms that exploit evolutionary information from multiple sequences. A
      consensus prediction is also returned which improves the average Q3 accuracy of
      prediction by 1% to 72.9%. The server simplifies the use of current prediction
      algorithms and allows conservation patterns important to structure and function
      to be identified. AVAILABILITY: http://barton.ebi.ac.uk/servers/jpred.h tml
      CONTACT: geoff@ebi.ac.uk

PMID- 9927722
TI  - Yeast forward and reverse 'n'-hybrid systems.
AB  - Since its original description almost 10 years ago, the yeast two-hybrid system
      has been used extensively to identify protein-protein interactions from many
      different organisms. Simultaneously, a number of 'variations on a theme' based on
      the original concept have been described. In one set of variations, systems were
      developed to detect other macromolecular interactions: DNA-protein (one-hybrid),
      RNA-protein (RNA-based three-hybrid) and small molecule-protein interactions
      (ligand-based three-hybrid). These different versions are collectively referred
      to here as 'n-hybrid systems'. In another set of variations, the original
      configuration of the two-hybrid fusion proteins was modified to expand the range
      of possible protein-protein interactions that could be analyzed. For example,
      systems were developed to detect trimeric interactions, ligand-receptor
      interactions or interactions that require particular post-translational
      modifications. Finally, the original concept was turned upside down and 'reverse
      n-hybrid systems' were developed to identify mutations, peptides or small
      molecules that dissociate macromolecular interactions. These reagents can be used
      to validate, in the relevant biological systems, the potential interactions
      identified with the 'forward n-hybrid systems'. The powerful genetic selections
      of the forward and reverse n-hybrid systems are proving useful in proteomic
      projects aimed at generating macromolecular interaction maps.

PMID- 9927723
TI  - A general model for site-specific recombination by the integrase family
      recombinases.
AB  - We present here a general model for integrase family site-specific recombination
      using the geometric relationships of the cleavable phosphodiester bonds and the
      disposition of the recombinase monomers (defined by their binding planes) with
      respect to them. The 'oscillation model' is based largely on the conformations of
      the recombinase-bound DNA duplexes and their dynamics within Holliday junctions.
      The duplex substrate or the Holliday junction intermediate is capable of
      'oscillating' between two cleavage-competent asymmetric states with respect to
      corres-ponding chemically inert 'equilibrium positions'. The model accommodates
      several features of the Flp system and predicts two modes of DNA cleavage during
      a normal recombination event. It is equally applicable to other systems that
      mediate recombination across 6, 7 or 8 bp long strand exchange regions (or
      spacers). The model is consistent with approximately 0-1, 1-2 and 2-3 bp of
      branch migration during recombination reactions involving 6, 7 and 8 bp spacers,
      respectively.

PMID- 9927724
TI  - Delta ribozyme has the ability to cleave in transan mRNA.
AB  - We report here the first demonstration of the cleavage of an mRNA in trans by
      delta ribozyme derived from the antigenomic version of the human hepatitis delta
      virus (HDV). We characterized potential delta ribozyme cleavage sites within HDV
      mRNA sequence (i.e. C/UGN6), using oligonucleotide binding shift assays and
      ribonuclease H hydrolysis. Ribozymes were synthesized based on the structural
      data and then tested for their ability to cleave the mRNA. Of the nine ribozymes
      examined, three specifically cleaved a derivative HDV mRNA. All three active
      ribozymes gave consistent indications that they cleaved single-stranded regions.
      Kinetic characterization of the ability of ribozymes to cleave both the full
      length mRNA and either wild-type or mutant small model substrate suggests: (i)
      delta ribozyme has turnovers, that is to say, several mRNA molecules can be
      successively cleaved by one ribozyme molecule; and (ii) the substrate specificity
      of delta ribozyme cleavage is not restricted to C/UGN6. Specifically, substrates
      with a higher guanosine residue content upstream of the cleavage site (i.e.
      positions -4 to -2) were always cleaved more efficiently than wild-type
      substrate. This work shows that delta ribozyme constitutes a potential catalytic
      RNA for further gene-inactivation therapy.

PMID- 9927725
TI  - A'-form RNA double helix in the single crystal structure of r(UGAGCUUCGGCUC).
AB  - Here we demonstrate the presence of the A'-RNA conformation using the single
      crystal structure of a tridecamer: r(UGAGCUUCGGCUC). The average A'-RNA
      conformation deduced from X-ray fiber diffraction data had only been available
      previously, but now the presence of the A'-RNA conformation has been found in a
      single crystal structure for the first time. Statistical analysis showed that the
      A'-RNA conformation is distinguishable from the A-RNA conformation in a plot of
      the major groove width against the base pair inclination angle. The major groove
      of the A'-RNA conformation is wide enough to accommodate a protein or peptide
      while that of the A-RNA conformation is too narrow to do so. The presence of the
      A'-RNA conformation is significant for protein-RNA interaction.

PMID- 9927726
TI  - Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic
      (AP) sites in DNA.
AB  - Yeast Rad27 is a 5'-->3' exonuclease and a flap endo-nuclease. Apn1 is the major
      apurinic/apyrimidinic (AP) endonuclease in yeast. The rad27 deletion mutants are
      highly sensitive to methylmethane sulfonate (MMS). By examining the role of Rad27
      in different modes of DNA excision repair, we wish to understand why the
      cytotoxic effect of MMS is dramatically enhanced in the absence of Rad27. Base
      excision repair (BER) of uracil-containing DNA was deficient in rad27 mutant
      extracts in that (i) the Apn1 activity was reduced, and (ii) after DNA incision
      by Apn1, hydrolysis of 1-5 nucleotides 3' to the baseless sugar phosphate was
      deficient. Thus, some AP sites may lead to unprocessed DNA strand breaks in rad27
      mutant cells. The severe MMS sensitivity of rad27 mutants is not caused by a
      reduction of the Apn1 activity. Surprisingly, we found that Apn1 endonuclease
      sensitizes rad27 mutant cells to MMS. Deleting the APN1 gene largely restored the
      resistance of rad27 mutants to MMS. These results suggest that unprocessed DNA
      strand breaks at AP sites are mainly responsible for the MMS sensitivity of rad27
      mutants. In contrast, nucleotide excision repair and BER of oxidative damage were
      not affected in rad27 mutant extracts, indicating that Rad27 is specifically
      required for BER of AP sites in DNA.

PMID- 9927727
TI  - The H-phosphonate approach to the solution phase synthesis of linear and cyclic
      oligoribonucleotides.
AB  - The solution phase synthesis of the tetraribonucleoside triphosphate r(ApCpGpU)
      18 and the corresponding cyclic tetraribonucleotide 19 is described. The
      synthetic methodology is based on 5'- O -(DMTr)-2'- O -(Fpmp)-ribonucleoside-3'-
      H -phosphonate building blocks 10. Coupling, which is rapid and quantitative, is
      effected with di-(2-chlorophenyl) phosphorochloridate 5 at -40 degreesC; it is
      followed by in situ treatment with 2-(4-methyl-phenyl)sulphanyl-1 H -isoindole
      1,3(2 H )-dione 6b. The resulting sulphur transfer reaction also proceeds rapidly
      and quantitatively at -40 degreesC. The same coupling and sulphur transfer steps
      are used in the cyclization reaction, but a 5'- H -phosphonate intermediate 24 is
      involved. The final three-step unblocking process involves treatment with (i) E 
      2-nitrobenzaldoxime 7 and N 1, N 1, N 3, N 3-tetramethylguanidine (TMG) 8 in
      aceto-nitrile, (ii) concentrated aqueous ammonia at 50 degreesC and (iii) 0.5
      mol/dm3sodium acetate buffer (pH 4.0) at 40 degreesC. The fully unblocked
      products 18 and 19 were characterized by NMR spectroscopy and by enzymatic
      digestion.

PMID- 9927728
TI  - Molecular basis for the enantioselectivity of HIV-1 reverse transcriptase: role
      of the 3'-hydroxyl group of the L-(beta)-ribose in chiral discrimination between
      D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphate analogs.
AB  - In order to identify the basis for the relaxed enantio-selectivity of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and to evaluate
      possible cross-resistance patterns between L-nucleoside-, D-nucleoside- and non
      nucleoside RT inhibitors, to be utilised in anti-HIV-1 combination therapy, we
      applied an in vitro approach based on the utilisation of six recom-binant HIV-1
      RT mutants containing single amino acid substitutions known to confer Nevirapine
      resistance in treated patients. The mutants were compared on different RNA/DNA
      and DNA/DNA substrates to the wild type (wt) enzyme for their sensitivity towards
      inhibition by the D- and L-enantiomers of 2'-deoxy- and 2',3'-dideoxynucleoside
      triphosphate analogs. The results showed that the 3'-hydroxyl group of the L
      (beta)-2'-deoxyribose moiety caused an unfavourable steric hindrance with critic
      residues in the HIV-1 RT active site and this steric barrier was increased by the
      Y181I mutation. Elimination of the 3'-hydroxyl group removed this hindrance and
      significantly improved binding to the HIV-1 RT wt and to the mutants. These
      results demonstrate the critical role of both the tyrosine 181 of RT and the 3'
      position of the sugar ring, in chiral discrimination between D- and L-nucleoside
      triphosphates. Moreover, they provide an important rationale for the combination
      of D- and L-(beta)-dideoxynucleoside analogs with non-nucleoside RT inhibitors in
      anti-HIV chemotherapy, since non-nucleosideinhibitors resistance mutations did
      not confer cross-resistance to dideoxynucleoside analogs.

PMID- 9927729
TI  - Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base
      excision repairenzyme thymine glycol DNA glycosylase.
AB  - An ionizing radiation-induced DNA lesion, thymine glycol, is removed from DNA by
      a thymine glycol DNA glycosylase with an apurinic/apyrimidinic (AP) lyase
      activity encoded by the Escherichia coli endonuclease III ( nth ) gene and its
      homolog in humans. Cells from Cockayne syndrome patients with mutations in the
      XPG gene show approximately 2-fold reduced global repair of thymine glycol.
      Hence, I decided to investigate the molecular mechanism of the effect of XPG
      protein observed in vivo on thymine glycol removal by studying the interactions
      of XPG protein and human endonuclease III (HsNTH) protein in vitro and the effect
      of XPG protein on the activity of HsNTH protein on a substrate containing thymine
      glycol. The XPG protein stimulates the binding of HsNTH protein to its substrate
      and increases its glycosylase/AP lyase activity by a factor of approximately 2
      through direct interaction between the two proteins. These results provide in
      vitro evidence for a second function of XPG protein in DNA repair and a
      mechanistic basis for its stimulatory activity on HsNTH protein.

PMID- 9927730
TI  - Human DNA topoisomerase IIbeta binds and cleaves four-way junction DNA in vitro.
AB  - We have used gel retardation analysis to show that human DNA topoisomerase IIbeta
      can bind a 40 bp linear duplex containing a single DNA topoisomerase IIbeta
      cleavage site. Furthermore, we demonstrate for the first time that human DNA
      topoisomerase IIbeta binds to four-way junction DNA. This supports previous
      suggestions that topoisomerase II may be targeted to supercoiled DNA through the
      recognition of DNA cruciforms, helix-helix crossovers and hairpins. DNA
      topoisomerase IIbeta had a 4-fold higher affinity for the four-way junction than
      for the linear duplex, as demonstrated by protein titration and competition
      analysis. Furthermore, the DNA topoisomerase IIbeta:four-way junction complex was
      significantly more salt stable than the complex with linear DNA. The four-way
      junction contained potential topoisomerase IIbeta cleavage sites straddling the
      points of strand exchange, and indeed, topoisomerase IIbeta was able to cleave
      three of these four predicted sites. This indicates that topoiso-merase IIbeta
      can bind to the centre of the junction. Topoisomerase II has to bind both the
      transported and the gated DNA helices prior to strand passage, and it is possible
      that both helices are provided by the four-way junction in this case. The stable
      complex of DNA topoisomerase IIbeta with four-way junction DNA may provide an
      ideal substrate for further studies into the mechanism of substrate recognition
      and binding by DNA topoisomerase II.

PMID- 9927732
TI  - Energetic and binding properties of DNA upon interaction with dodecyl
      trimethylammonium bromide.
AB  - The interaction of dodecyl trimethylammonium bromide (DTAB), a cationic
      surfactant, with calf thymus DNA has been studied by various methods, including
      potentiometric technique using DTAB-selective plastic membrane electrode at 27
      and 37 degreesC, isothermal titration microcalorimetry and UV spectrophotometry
      at 27 degreesC using 0.05 M Tris buffer and 0.01 M NaCl at pH 7.4. The free
      energy is calculated from binding isotherms on the basis of Wyman binding
      potential theory and the enthalpy of binding according to van't Hoff relation.
      The enthalpy of unfolding has been determined by subtraction of the enthalpy of
      binding from the microcalorimetric enthalpy. The results show that, after the
      interaction of first DTAB molecule to DNA (base molarity) through the
      electrostatic interaction, the second DTAB molecule also binds to DNA through
      electrostatic interaction. At this stage, the predom-inant DNA conformational
      change occurs. Afterwards up to 20 DTAB molecules, below the critical micelle
      concentration of DTAB, bind through hydrophobic interactions.

PMID- 9927731
TI  - A new human topoisomerase III that interacts with SGS1 protein.
AB  - Eukaryotic DNA topoisomerase III was first identified by studying the hyper
      recombination and slow growth phenotypes of yeast mutants. Topoisomerase III
      interacts with DNA helicase SGS1 and the two proteins are involved in DNA
      recombination, cellular aging and maintenance of genome stability. A human
      homolog of topoisomerase III has previously been identified. Here we report the
      identification of cDNAs and the determination of gene structure for a second
      human topoisomerase III gene. This novel gene expresses three alternatively
      spliced transcripts, which encode gene products different in the putative DNA
      binding C-termini. The largest gene product of the novel topoisomerase III was
      expressed and shown to interact with SGS1 protein and partially rescue the slow
      growth defect of a yeast topoisomerase III mutant. The presence of more than one
      human topoisomerase III is reminiscent of mammalian topoisomerase II, which has
      two genetically distinct isoforms with different expression patterns and probably
      different functions in mammalian cells.

PMID- 9927733
TI  - Heterodimers of the SnoN and Ski oncoproteins form preferentially over homodimers
      and are more potent transforming agents.
AB  - sno is a member of the ski oncogene family and shares ski 's ability to transform
      avian fibroblasts and induce muscle differentiation. Ski and SnoN are
      transcription factors that form both homodimers and heterodimers. They recognize
      a specific DNA binding site (GTCTAGAC) through which they repress transcription.
      Efficient homodimerization of Ski, mediated by a bipartite C-terminal domain
      consisting of five tandem repeats (TR) and a leucine zipper (LZ), correlates with
      efficient DNA binding and cellular transformation. The present study assesses the
      role of SnoN homodimerization and SnoN:Ski heterodimerization in the activities
      of these proteins. Unlike Ski, efficient homodimerization by SnoN is shown to
      require an upstream region of the protein in addition to the TR/LZ domain.
      Deletion of the TR/LZ from SnoN decreases its activity in transcriptional
      repression and cellular transformation. When co-expressed in vitro, c-Ski and
      SnoN preferentially form heterodimers. In vivo, they form heterodimers that bind
      the GTCTAGAC element. Tethered Ski:Sno hetero-dimers that lack TR/LZ domains are
      more active than either their monomeric counterparts, tethered Ski:Ski homodimers
      or full-length SnoN and c-Ski. This work demonstrates, for the first time, the
      differences between dimer formation by Ski and SnoN and underscores the
      importance of dimerization in their activity.

PMID- 9927734
TI  - Synthesis and enzymatic processing of oligodeoxynucleotides containing tandem
      base damage.
AB  - Several studies have shown that ionizing radiation generates a wide spectrum of
      lesions to DNA including base modifications, abasic sites, strand breaks,
      crosslinks and tandem base damage. One example of tandem base damage induced by
      @OH radical inX-irradiated DNA oligomers is N -(2-deoxy-beta-d- erythro 
      pentofuranosyl)-formylamine/8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). In
      order to investigate the biological significance of such a tandem lesion, both 8
      oxo-7,8-dihydroguanine and formylamine were introduced into synthetic
      oligonucleotides at vicinal positions using the solid phase phosphoramidite
      method. For this purpose, a new convenient method of synthesis of 8-oxodGuo was
      developed. The purity and integrity of the modified synthetic DNA fragments were
      assessed using different complementary techniques including HPLC, polyacrylamide
      gel electrophoresis, electrospray and MALDI-TOF mass spectrometry. The piperidine
      test applied to the double modified base-containing oligonucleotides revealed the
      high alkaline lability of formylamine in DNA. In addition, various enzymatic
      experiments aimed at determining biochemical features of such multiply damaged
      sites were carried out using the synthetic substrates. The pro-cessing of the
      vicinal lesions by nuclease P1, snake venom phosphodiesterase, calf spleen
      phospho-diesterase and repair enzymes including Escherichia coli endonuclease
      (endo) III and Fapy-glycosylase was studied and is reported.

PMID- 9927735
TI  - A human U2 RNA mutant stalled in 3' end processing is impaired in nuclear import.
AB  - The biosynthesis of U1, U2, U4 and U5 spliceosomal small nuclear RNAs (snRNAs)
      involves the nuclear export of precursor molecules extended at their 3' ends,
      followed by a cytoplasmic phase during which the pre-snRNAs assemble into
      ribonucleoprotein particles and undergo hypermethylation of their 5' caps and 3'
      end processing prior to nuclear import. Previous studies have demonstrated that
      the assembly of pre-snRNAs into ribonucleoprotein particles containing the Sm
      core proteins is essential for nuclear import in mammalian cells but that 5' cap
      hypermethylation is not. In the present investigation we have asked whether or
      not 3' end processing is required for nuclear import of U2 RNA. We designed human
      pre-U2 RNAs that carried modified 3' tails, and identified one that was stalled
      (or greatly slowed) in 3' end processing, leading to its accumulation in the
      cytoplasm of human cells. Nonetheless, this 3' processing arrested pre-U2 RNA
      molecule was found to undergo cytoplasmic assembly into Sm protein-containing
      complexes to the same extent as normal pre-U2 RNA. The Sm protein-associated,
      unprocessed mutant pre-U2 RNA was not observed in the nuclear fraction. Using an
      assay based on suppression of a genetically blocked SV40 pre-mRNA splicing
      pathway, we found that the 3' processing deficient U2 RNA was significantly
      reduced in its ability to rescue splicing, consistent with its impaired nuclear
      import.

PMID- 9927736
TI  - Substrate recognition by the Pvu II endonuclease: binding and cleavage of
      CAG5mCTG sites.
AB  - The Pvu II restriction endonuclease (R. Pvu II) cleaves CAG downward arrowCTG
      sequences as indicated, leaving blunt ends. Its cognate methyltransferase (M. Pvu
      II) generates N4-methylcytosine, yielding CAGN4mCTG, though the mechanism by
      which this prevents cleavage by R. Pvu II is unknown. The heterologous 5
      methylcytosinemethylation CAG5mCTG has also been reported to prevent cleavage by
      R. Pvu II and this has been used in some cloning methods. Since this
      heterologousmethylation occurs at the native methylated base, it can provide
      insights into the detection of DNAmethylation by R. Pvu II. We found that the
      cloned gene for R. Pvu II could not stably transform cells protected only by M.
      Alu I (AG5mCT) and then determined that R. Pvu II cleaves CAG5mCTG in vitro, even
      when both strands are methylated. DNase I footprint analysis and competition
      experiments reveal that R. Pvu II binds to CAG5mCTG specifically, though with
      reduced affinity relative to the unmethylated sequence. These results provide
      biochemical support for the publishedstructures of R. Pvu II complexed with DNA
      containing CAGCTG and CAG5-iodoCTG and support a model for how methylation
      interferes with DNA cleavage by this enzyme.

PMID- 9927737
TI  - DNA cleavage and degradation by the SbcCD protein complex from Escherichia coli.
AB  - The SbcCD protein is a member of a group of nucleases found in bacteriophage T4
      and T5, eubacteria, archaebacteria, yeast, Drosophila, mouse and man. Evidence
      from electron microscopy has revealed a distinctive structure consisting of two
      globular domains linked by a long region of coiled coil, similar to that
      predicted for the members of the SMC family. That a nuclease should have such an
      unusual structure suggests that its mode of action may be complex. Here we show
      that the protein degrades duplex DNA in a 3'-->5' direction. This degradation
      releases products half the length of the original duplex suggesting simultaneous
      degradation from two duplex ends. This may provide a link to the unusual
      structure of the protein since our data are consistent with recognition and
      cleavage of DNA ends followed by 3'-->5' nicking by two nucleolytic centres
      within a single nuclease molecule that releases a half length limit product. We
      also show that cleavage is not simply at the point of a single-strand/double
      stand transition and that despite the dominant 3'-->5' polarity of degradation, a
      5' single-strand can be cleaved when attached to duplex DNA. The implications of
      this mechanism for the processing of hairpins formed during DNA replication are
      discussed.

PMID- 9927738
TI  - Sequence divergence of the RNA polymerase shared subunit ABC14.5 (Rpb8)
      selectively affects RNA polymerase III assembly in Saccharomyces cerevisiae.
AB  - ABC14.5 (Rpb8) is a eukaryotic subunit common to all three nuclear RNA
      polymerases. In Saccharomyces cerevisiae, ABC14.5 (Rpb8) is essential for cell
      viability, however its function remains unknown. We have cloned and characterised
      the Schizosaccharomyces pombe rpb8(+) cDNA. We found that S.pombe rpb8, unlike
      the similarly diverged human orthologue, cannot substitute for S.cerevisiae
      ABC14. 5 in vivo. To obtain information on the function of this RNA polymerase
      shared subunit we have used S.pombe rpb8 as a naturally altered molecule in
      heterologous expression assays in S.cerevisiae. Amino acid residue differences
      within the 67 N-terminal residues contribute to the functional distinction of the
      two yeast orthologues in S.cerevisiae. Overexpression of the S.cerevisiae largest
      subunit of RNA polymerase III C160 (Rpc1) allows S.pombe rpb8 to functionally
      replace ABC14.5 in S.cerevisiae, suggesting a specific genetic interaction
      between the S.cerevisiae ABC14.5 (Rpb8) and C160 subunits. We provide further
      molecular and biochemical evidence showing that the heterologously expressed
      S.pombe rpb8 molecule selectively affects RNApolymerase III but not RNA
      polymerase I complex assembly. We also report the identification of a
      S.cerevisiae ABC14.5-G120D mutant which affects RNA polymerase III.

PMID- 9927739
TI  - Random mutagenesis by recombinational capture of PCR products in Bacillus
      subtilis and Acinetobacter calcoaceticus.
AB  - We describe a general method for random mutagenesis of cloned genes by error
      prone PCR or DNA shuffling that eliminates the need for post-amplification
      subcloning following each cycle of mutagenesis. This method exploits the highly
      efficient and recombinogenic nature of DNA uptake during natural transformation
      in the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium
      Acinetobacter calcoaceticus. Plasmid systems were designed that allow capture of
      PCR-amplified DNA fragments by marker-replacement recombination with a
      structurally similar helper plasmid resident in the transformation recipient.
      This recombination event simultaneously transfers the amplified sequences into
      the helper plasmid and restores the integrity of a drug resistance gene, thereby
      affording a direct selection for fragment capture. Although this strategy was
      sufficiently effective to permit recovery in B. subtilis of up to 10(3)
      transformants/microgram of PCR product, equivalent plasmid systems were
      approximately 100 times more efficient in A.calcoaceticus. Acinetobacter
      calcoaceticus also offers the advantage of essentially constitutive
      transformation competence in ordinary complex broth, such as LB, in contrast to
      two-step growth in semi-synthetic media required for optimal transformation of
      B.subtilis.

PMID- 9927740
TI  - The salt dependence of DNA recognition by NF-kappaB p50: a detailed kinetic
      analysis of the effects on affinityand specificity.
AB  - The binding kinetics of NF-kappaB p50 to the Ig-kappaB site and to a DNA duplex
      with no specific binding site were determined under varying conditions of
      potassium chloride concentration using a surface plasmonresonance biosensor.
      Association and dissociation rate constants were measured enabling calculation of
      the dissociation constants. Under previously established high affinity buffer
      conditions, the k a for both sequences was in the order of 10(7) M-1s-1whilst the
      k d values varied 600-fold in a sequence-dependent manner between 10(-1) and 10(
      4 )s-1, suggesting that the selectivity of p50 for different sequences is
      mediated primarily through sequence-dependent dissociation rates. The calculated
      K D value for the Ig-kappaB sequence was 16 pM, whilst the K D for the non
      specific sequence was 9.9 nM. As the ionic strength increased to levels which are
      closer to that of the cellular environment, the binding of p50 to the non
      specific sequence was abolished whilst the specific affinity dropped to nanomolar
      levels. From these results, a mechanism is proposed in which p50 binds specific
      sequences with high affinity whilst binding non-specific sequences weakly enough
      to allow efficient searching of the DNA.

PMID- 9927741
TI  - Conserved features of Y RNAs revealed by automated phylogenetic secondary
      structure analysis.
AB  - Y RNAs are small 'cytoplasmic' RNAs which are components of the Ro
      ribonucleoprotein (RNP) complex. The core of this complex, which is found in the
      cell nuclei of higher eukaryotes as well as the cytoplasm, is composed of a
      complex between the 60 kDa Ro protein and Y RNAs. Human cells contain four
      distinct Y RNAs (Y1, Y3, Y4 and Y5), while other eukaryotes contain a variable
      number of Y RNA homologues. When detected in a particular species, the Ro RNP has
      been present in every cell type within that particular organism. This
      characteristic, along with its high conservation among vertebrates, suggests an
      important function for Ro RNP in cellular metabolism; however, this function has
      not yet been definitively elucidated. In order to identify conserved features of
      Y RNA sequences and structures which may be directly involved in Ro RNP function,
      a phylogenetic comparative analysis of Y RNAs has been performed. Sequences of Y
      RNA homologues from five vertebrate species have been obtained and, together with
      previously published Y RNA sequences, used to predict Y RNA secondary structures.
      A novel RNA secondary structure comparison algorithm, the suboptimal RNA analysis
      program, has been developed and used in conjunction with available algorithms to
      find phylogenetically conserved secondary structure models for YI, Y3 and Y4
      RNAs. Short, conserved sequences within the Y RNAs have been identified and are
      invariant among vertebrates, consistent with a direct role for Y RNAs in Ro
      function. A subset of these are located wholly or partially in looped regions in
      the Y3 and Y4 RNA predicted model structures, in accord with the possibility that
      these Y RNAs base pair with other cellular nucleic acids or are sites of
      interaction between the Ro RNP and other macromolecules.

PMID- 9927742
TI  - cDNA fingerprinting of osteoprogenitor cells to isolate differentiation stage
      specific genes.
AB  - A cDNA fingerprinting strategy was developed to identify genes based on their
      differential expression pattern during osteoblast development. Preliminary
      biological and molecular staging of cDNA pools prepared by global amplification
      PCR allowed discrim-inating choices to be made in selection of expressed sequence
      tags (ESTs) to be isolated. Sequencing of selected ESTs confirmed that both known
      and novel genes can be isolated from any developmental stage of interest, e.g.
      from primitive progenitors, intermediate precursors or mature osteoblasts. EST
      expression provides insight into possible interrelated physiological functions
      and putative interacting molecules during differentiation. This method offers a
      functional genomics approach to isolate differentiation stage-specific genes in
      samples as small as a single cell.

PMID- 9927743
TI  - Visualizing tertiary folding of RNA and RNA-protein interactions by a tethered
      iron chelate: analysis ofHIV-1 Tat-TAR complex.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) requires specific
      interactions of Tat protein with the trans -activation responsive region (TAR)
      RNA, a 59 base stem-loop structure located at the 5'-end of all HIV transcripts.
      We have used an intramolecular RNA self-cleaving strategy to determine the
      folding of TAR RNA and its interactions with a Tat peptide. We incor-porated an
      EDTA analog at position 24 in the HIV-1 Tat binding site of the TAR RNA. After
      isolation and purification of the EDTA-TAR conjugate, RNA self-cleavage was
      initiated by the addition of an iron salt, ascorbate and hydrogen peroxide.
      Hydroxyl radicals generated from the tethered Fe(II) cleaved TAR RNA backbone in
      two localized regions. Sites of RNA cleavage were mapped by sequencing reactions.
      A Tat fragment, Tat(38-72), specifically inhibited RNA self-cleavage. To
      determine the structural changes caused by the Tat peptide, we performed Fe(II)
      EDTA footprinting experiments on Tat-TAR complex. Our high-resolution
      footprinting results suggest that the inhibition of self-cleavage of EDTA-TAR is
      due to two effects of Tat binding: (i) Tat binds in the bulge and protects
      residues in the vicinity of the bulge from self-cleavage and (ii) RNA goes
      through a structural change where EDTA-U24 is rigidly positioned out of the helix
      and cannot get access to other nucleotides in the loop of TAR RNA, which are not
      protected by the Tat peptide. Our results demonstrate that Fe(II)-EDTA-mediated
      RNA self-cleavage can be applied to study RNA tertiary structures and RNA-protein
      interactions.

PMID- 9927745
TI  - DNA binding specificity and transactivation properties of SREBP-2 bound to
      multiple sites on the human apoA-II promoter.
AB  - DNase I footprinting of the apoA-II promoter using sterol regulatory element
      binding protein-2 [(SREBP-2 (1-458)] expressed in bacteria identified four
      protected regions, designated AIIAB (-64 to -48), AIICD (-178 to -154), AIIDE (
      352 to -332) and AIIK (-760 to -743), which bind SREBP-2 and contain either
      palindromic or direct repeat motifs. Potassium permanganate and dimethyl sulfate
      interference experiments using the AIIAB region as probe showed that the
      nucleotides of a decameric palindromic repeat RTCAMVTGMY and two 5' T residues
      participate in DNA-protein interactions. SREBP-2 transactivated the intact (
      911/+29) apoA-II promoter 1.7-fold and truncated apoA-II promoter segments which
      contain one, two or three SREBP-2 sites 11- to 17-fold in HepG2 cells.
      Transactivation of a promoter construct containing the binding site AIIAB and the
      apoA-II enhancer, which includes the binding site AIIK, was abolished by
      mutations in element AIIAB. An SREBP-2 mutant defective in DNA binding caused a
      dose-dependent repression of the apoA-II promoter activity. Repression was also
      caused by an SREBP-2 mutant which lacks the N-terminal activation domain
      (residues 1-93) but binds normally to its cognate sites. In contrast, a double
      SREBP-2 mutant which lacks both the DNA binding and the activation domains has no
      effect on the apoA-II promoter activity. Overall, the findings suggest that SREBP
      2 can transactivate the apoA-II promoter by binding to multiple sites.
      Furthermore, the repression caused by the DNA binding deficient mutants results
      from squelching of positive activator(s) which appear to recognize the activation
      domain of SREBP-2.

PMID- 9927744
TI  - Vaccine candidate MSP-1 from Plasmodium falciparum: a redesigned 4917 bp
      polynucleotide enables synthesis and isolation of full-length protein from
      Escherichia coli and mammalian cells.
AB  - The Plasmodium falciparum malaria parasite is the causative agent of malaria
      tropica. Merozoites, one of the extracellular developmental stages of this
      parasite, expose at their surface the merozoite surface protein-1 complex (MSP
      1), which results from the proteolytic processing of a 190-200 kDa precursor. MSP
      1 is highly immunogenic in humans and numerous studies suggest that this protein
      is an effective target for a protective immune response. Although its function is
      unknown, there are indications that it may play a role during invasion of
      erythrocytes by merozoites. The parasite-derived msp-1 gene, which is
      approximately 5000 bp long, contains 74% AT. This high AT content has prevented
      stable cloning of the full-size gene in Escherichia coli and consequently its
      expression in heterologous systems. Here, we describe the synthesis of a 4917 bp
      gene encoding MSP-1 from the FCB-1 strain of P. falciparum adjusted for human
      codon preferences. The synthetic msp-1 gene (55% AT) was cloned, maintained and
      expressed in its entirety in E.coli as well as in CHO and HeLa cells. The
      purified protein is soluble and appears to possess native conformation because it
      reacts with a panel of mAbs specific for conformational epitopes. The strategy we
      used for synthesizing the full-length msp-1 gene was toassemble it from DNA
      fragments encoding all of the major proteolytic fragments normally generated at
      the parasite's surface. Thus, after subcloning we also obtained each of these MSP
      1 processing products as hexahistidine fusion proteins in E.coli and isolated
      them by affinity chromatography on Ni2+agarose. The availability of defined
      preparations of MSP-1 and its major processing products open up new possibilities
      for in-depth studies at the structural and functional level of this important
      protein, including the exploration of MSP-1-based experimental vaccines.

PMID- 9927746
TI  - Thermodynamics of RNA hairpins containing single internal mismatches.
AB  - Thermodynamic parameters and circular dichroism spectra are presented for RNA
      hairpins containing single internal mismatches in the stem regions. Three
      different sequence contexts for the G*U mismatch and two contexts for C*A, G*A,
      U*U, A*C and U*G mismatches were examined and compared with Watson-Crick base
      pair stabilities. The RNA hairpins employed were a microhelix and tetraloop
      representing the Escherichia coli tRNAAlaacceptor stem and sequence variants that
      have been altered at the naturally occurring G*U mismatch site. UV melting
      studies were carried out under different conditions to evaluate the effects of
      sodium ion concentration and pH on the stability of mismatch-containing hairpins.
      Our main findings are that single internal mismatches exhibit a range of effects
      on hairpin stability. In these studies, the size and sequence of the loop and
      stem are shown to influence the overall stability of the RNA, and have a minor
      effect on the relative mismatch stabilities. The relationship of these results to
      RNA-ligand interactions involving mismatch base-pairs is discussed.

PMID- 9927747
TI  - Control of 3' splice site choice in vivo by ASF/SF2 and hnRNP A1.
AB  - The constitutive splicing factor ASF/SF2 has been shown to affect the choice
      between alternative splice sites by favoring the proximal as opposed to the
      distal choice. HnRNP A1 antagonizes ASF/SF2 by promoting the distal choice for
      competing 5' splice sites. We have tested the in vivo effects of these proteins
      on alternative 3' splice site choices. Cotransfection of a dihydrofolate
      reductase-calcitonin chimeric construct togetherwith a plasmid specifying the SR
      protein ASF/SF2 into cells of several mammalian lines increased use of a proximal
      3' splice site, resulting in the inclusion of a terminal calcitonin exon. This
      stimulation of 3' proximal splicing was antagonized by cotransfection with an
      hnRNP A1 plasmid. This effect of hnRNP A1 in promoting distal splicing was also
      seen in an hnRNP A1-deficient MEL cell line. A similar effect of hnRNP A1 was
      demonstrated with mutant hamster adenine phosphoribosyltransferase (aprt)
      transcripts that are normally constitutively spliced, suggesting that hnRNP A1
      may be a general inhibitor of proximal splicing. Intron size also influenced
      splice site choice in mutant aprt transcripts, with larger introns favoring
      proximal splicing. These results support the idea that the ratios of particular
      but general splicing factors and hnRNPs play a role in alternative splicing.

PMID- 9927748
TI  - Effect of base analog substitutions in the specific GATC site on binding and
      methylation of oligonucleotide duplexes by the bacteriophage T4 Dam DNA-[N6
      adenine] methyltransferase.
AB  - The interaction of the phage T4 Dam DNA-[N6-adenine] methyltransferase with 24mer
      synthetic oligonucleotide duplexes having different purine base substitutions in
      the palindromic recognition sequence, GATC, was investigated by means of gel
      shift and methyl transfer assays. The substitutions were introduced in either the
      upper or lower strand: guanine by 7-deazaguanine (G-->D) or 2-aminopurine (G-->N)
      and target adenine by purine (A-->P) or 2-aminopurine (A-->N). The effects of
      each base modification on binding/methylation were approximately equivalent for
      both strands. G-->D and G-->N substitutions resulted in a sharp decrease in
      binary complex formation. This suggests that T4 Dam makes hydrogen bonds with
      either the N7- or O6-keto groups (or both) in forming the complex. In contrast, A
      ->P and A-->N substitutions were much more tolerant for complex formation. This
      confirms our earlier observations that the presence of intact 5'-G:C base pairs
      at both ends of the methylation site is critical, but that base substitutions
      within the central A:T base pairs show less inhibition of complex formation.
      Addition of T4 Dam to a complete substrate mixture resulted in a burst of
      [3H]methylated product. In all cases the substrate dependencies of bursts and
      methylation rates were proportional to each other. For the perfect 24mer k cat =
      0.014/s and K m = 7.7 nM was obtained. In contrast to binary complex formation
      the two guanine substitutions exerted relatively minor effects on catalytic
      turnover (the k cat was reduced at most 2. 5-fold), while the two adenine
      substitutions showed stronger effects (5- to 15-fold reduction in k cat). The
      effects of base analog substitutions on K m(DNA) were more variable: A-->P
      (decreased); A-->N and G-->D (unchanged); G-->N (increased).

PMID- 9927749
TI  - The geometry of a synaptic intermediate in a pathway of bacteriophage lambda site
      specific recombination.
AB  - Bacteriophage lambda uses site-specific recombination to move its DNA into and
      out of the Escherichia coli genome. The recombination event is mediated by the
      phage-encoded integrase (Int) at short DNA sequences known as attachment ( att )
      sites. Int catalyzes recombination via at least four distinct pathways,
      distinguishable by their requirements for accessory proteins and by the sequence
      of their substrates. The simplest recombination reaction catalyzed by Int does
      not require any accessory proteins and takes place between two attL sites. This
      reaction proceeds through an intermediate known as the straight-L bimolecular
      complex (SL-BMC), a stable complex which contains two attL sites synapsed by Int.
      We have investigated the orientation of the two substrates in the SL-BMC with
      respect to each other using two independent direct methods, a ligation assay and
      visualization by atomic force microscopy (AFM). Both show that the two DNA
      substrates in the complex are arranged in a tetrahedral or nearly square planar
      alignment skewed towards parallel. The DNA molecules in the complex are bent.

PMID- 9927750
TI  - Telomerase protein rather than its RNA is the target of phosphorothioate-modified
      oligonucleotides.
AB  - Human telomerase is a ribonucleoprotein which uses its internal RNA moiety as a
      template for telomeric DNA synthesis. This enzyme is up-regulated in most
      malignant tumors and is therefore considered as a possible cancer target. Here we
      examined the effects of differently modified oligomers on telomeraseactivity from
      HL-60 cell extracts (TRAP-ezetrade mark assay). Phosphorothioate-modified
      oligonucleotides (PS-ODNs) inhibited telomerase activity at subnanomolar concen
      trations and proved to be more efficient than peptide nucleic acids. In contrast
      to all the investigated oligomers, PS-ODNs were found to bind to the protein
      motif of telomerase called the primer binding site but poorly to its RNA. This is
      suggested by kinetic investigations demonstrating a competitive interaction of PS
      ODNs and TS primer at the primer binding site. The K m value of the TS primer was
      10.8 nM, the K i value of a 20mer PS-ODN was 1.6 nM. When the TS primer was PS
      modified a striking increase in the telomerase activity was found which
      correlates with the number of phosphodiesters replaced. The K m value of a
      completely PS-modified TS primer was 0.56 nM. Based on these results the design
      of chimeric ODNs is proposed consisting of a 5'-PS-modified part targeting the
      primer binding site and a 3'-terminus part targeting the telomerase RNA.

PMID- 9927751
TI  - 3'-Terminal RNA structures and poly(U) tracts inhibit initiation by a 3'-->5'
      exonuclease in vitro.
AB  - We have previously shown that the presence of a poly(A) tail blocks the activity
      of a highly efficient 3'-->5' exonuclease in HeLa extracts. Similar activities
      have been implicated in RNA turnover in vivo. It is not clear, however, what
      protects poly(A)-non-mRNAs from the action of this enzyme. A stem-loop structure
      located at the 3'-end of U11 RNA was required to protect this transcript from the
      exonuclease in vitro. Similar 3' stem-loop structures, or extensive base
      pairinginvolving the 3'-end, are present on all mature small stable RNAs. The
      placement of artificial stem-loop structures at the 3'-end also protected RNA
      substrates, suggesting that RNA structure alone is sufficient to block the
      initiation of the exonuclease. The placement of RNA structures at internal
      positions of substrate trans-cripts did not affect the activity of the
      exonuclease or lead to the accumulation of degradation intermediates. Pol III
      precursor transcripts contain short poly(U) tracts rather than structure at their
      3'-ends. Terminal poly(U) tracts protected RNA substrates from the 3'-->5'
      exonuclease in a protein-dependent fashion. Although La protein is found
      associated with the terminal U tracts of pol III precursor transcripts both in
      vivo and in vitro, La protein was not required for poly(U) to protect RNA
      substrates from the 3'-->5' exonuclease. In summary, these data reveal a variety
      of ways RNAs have evolved to protect themselves from this exonuclease.

PMID- 9927752
TI  - Phosphorylation of GATA-1 increases its DNA-binding affinity and is correlated
      with induction of human K562 erythroleukaemia cells.
AB  - We have investigated by electrophoretic mobility shift assay (EMSA) the level of
      GATA-1 DNA-binding activity in nuclear extracts prepared from the human
      erythroleukaemic cell line, K562, after erythroid induction by hemin, sodium
      butyrate (NaB) or Trichostatin A or treatment with N -acetylcysteine (NAC).
      Relative to extract from untreated cells, GATA-1 binding activity increased
      markedly in all cases. However, immunoblot analysis revealed unchanged levels of
      GATA-1 protein after induction. Incubation of induced but not uninduced K562
      extracts with phosphatase prior to EMSA weakened the binding activity, suggesting
      that the increase in GATA-1 binding following induction of K562 cells was a
      consequence of phosphorylation. When the mouse erythroleukaemic cell line MEL was
      induced with dimethylsulphoxide (DMSO), NaB or NAC, GATA-1 binding activity fell
      with DMSO, rose significantly with NaB and remained at about the same level in
      NAC-induced cells. In this case immunoblotting revealed that GATA-1 protein
      levels were in accord with the EMSA data. The DNA-binding activities of induced
      and uninduced MEL cell nuclear extracts were decreased by incubation with
      phosphatase, showing that phosphoryl-ation and DNA binding of GATA-1 are already
      optimalin these cells. The DNA-binding activity of affinity-purified GATA-1 from
      MEL cells was also reduced by phosphatase treatment, showing that
      phosphorylation/dephosphorylation is directly affecting the factor. Furthermore,
      when a comparison was made by EMSA of nuclear extracts prepared from K562 and MEL
      cells untreated or incubated with okadaic acid, a phosphatase inhibitor, GATA-1
      binding was seen to increase with K562 cells, whereas with MEL cells there was no
      change in GATA-1 binding. Overall the results suggest that the level of GATA-1
      phosphorylation increases after the induction of K562, but not MEL cells, where
      GATA-1 is already highly phosphorylated. Furthermore, phosphorylation increases
      the binding affinity of GATA-1 for a canonical binding site.

PMID- 9927753
TI  - Chromosomal mutations induced by triplex-forming oligonucleotides in mammalian
      cells.
AB  - Specific recognition of a region of duplex DNA by triplex-forming
      oligonucleotides (TFOs) provides an attractive strategy for genetic manipulation.
      Based on this, we have investigated the ability of the triplex-directed approach
      to induce mutations at a chromosomal locus in living cells. A mouse fibroblast
      cell line was constructed containing multiple chromosomal copies of the
      lambdasupFG1 vector carrying the supFG1 mutation-reporter gene. Cells were
      treated with specific (psoAG30) or control (psoSCR30) psoralen-conjugated TFOs in
      the presence and absence of UVA irradiation. The results demonstrated a 6- to 10
      fold induction of supFG1 mutations in the psoAG30-treated cells as compared with
      psoSCR30-treated or untreated control cells. Interestingly, UVA irradiation had
      no effect onthe mutation frequencies induced by the psoralen-conjugated TFOs,
      suggesting a triplex-mediated but photoproduct-independent process of
      mutagenesis. Sequencing data were consistent with this finding since the expected
      T.A-->A.T transversions at the predicted psoralen crosslinking site were not
      detected. However, insertions and deletions were detected within the triplex
      binding site, indicating a TFO-specific induction of mutagenesis. This result
      demonstrates the ability of triplex-forming oligonucleotides to influence
      mutation frequencies at a specific site in a mammalian chromosome.

PMID- 9927754
TI  - Mutational analysis of the engrailed homeodomain recognition helix by phage
      display.
AB  - The homeodomain (HD) is a ubiquitous protein fold that confers DNA binding
      function on a superfamily of eukaryotic gene regulatory proteins. Here, the DNA
      binding of recognition helix variants of the HD from the engrailed gene of
      Drosophila melanogaster was investigated by phage display. Nineteen different
      combinations of pairwise mutations at positions 50 and 54 were screened against a
      panel of four DNA sequences consisting of the engrailed consensus, a non-specific
      DNA control based on the lambda repressor operator OR1 and two model sequence
      targets con-taining imperfect versions of the 5'-TAAT-3' consensus. The resulting
      mutant proteins could be divided into four groups that varied with respect to
      their affinity for DNA and specificity for the engrailed consensus. The altered
      specificity phenotypes of several mutant proteins were confirmed by DNA mobility
      shift analysis. Lys50/Ala54 was the only mutant protein that exhibited
      preferential binding to a sequence other than the engrailed consensus. Arginine
      was also demonstrated to be a functional replacement for Ala54. The functional
      combinations at 50 and 54 identified by these experiments recapitulate the
      distribution of naturally occurring HD sequences and illustrate how the engrailed
      HD can be used as a framework to explore covariation among DNA binding residues.

PMID- 9927755
TI  - Extinction of alpha1-antitrypsin expression in cell hybrids is independent of
      HNF1alpha and HNF4 and involves both promoter and internal DNA sequences.
AB  - In rat hepatoma x fibroblast somatic cell hybrids, extinction of rat alpha1
      antitrypsin (alpha1AT) gene expression is accompanied by the loss of liver
      enriched transcription factors hepatocyte nuclear factor 1 (HNF1alpha) and
      hepatocyte nuclear factor 4 (HNF4). Previous analysis showed that forced
      expression of functional HNF1alpha failed to prevent extinction of the rat
      alpha1AT locus in cell hybrids. Here I show that ectopic co-expression of
      HNF1alpha plus HNF4 fails to prevent extinction of either rat or human alpha1AT
      genes in cell hybrids. A 40 kb human alpha1AT minilocus integrated into the rat
      genome is fully silenced in cell hybrids in the presence of transacting factors.
      The integrated alpha1AT promoter, but not a viral or ubiquitously active
      promoter, is repressed 35-fold in the cell hybrids. In addition, position effects
      also contributed to extinction of many integrated transgenes in a cell type
      dependent manner. Finally, internal DNA sequences within the human alpha1AT gene
      contributed dramatically to the extinction phenotype, resulting in a further 10-
      to 30-fold reduction in alpha1AT gene expression in cell hybrids. Thus, multiple
      mechanisms contribute to silencing of tissue-specific gene expression of the
      alpha1AT gene in cell hybrids.

PMID- 9927756
TI  - Double strand break rejoining by mammalian mitochondrial extracts.
AB  - DNA end-joining was measured by incubating linearized plasmid DNA with
      mitochondrial protein extracts. A spectrum of end-joined molecules ranging from
      re-circularized monomer to dimer and higher molecular weight forms was observed.
      The DNA end-joining reaction required ATP and Mg2+, and was inhibited by sodium
      chloride. Both cohesive- and blunt-ended DNA molecules were end-joined, although
      the former were more efficient substrates. Molecular analysis of rejoined
      molecules revealed that >95% of the linearized DNA were precisely end-joined. The
      few imprecisely end-joined molecules recovered, sustained deletions that spanned
      direct repeat sequences. The deletions observed are strikingly similar to those
      present in mitochondrial genomes of patients with Kearns-Sayre or Pearson
      syndromes, certain ophthalmic myopathies and the aged. These results suggest that
      mammalian mitochondria possess a DNA double strand break repair activity similar
      to that seen in the nucleus, and that this repair pathway may play a role in the
      generation of mitochondrial DNA deletions associated with a number of human
      pathologies.

PMID- 9927757
TI  - Cellular regulation of ribosomal DNA transcription:both rat and Xenopus UBF1
      stimulate rDNA transcription in 3T3 fibroblasts.
AB  - A novel RNA polymerase I (RPI) driven reporter gene has been used to investigate
      the in vivo role of the architectural ribosomal transcription factor UBF in gene
      activation and species specificity. It is shown that the level of UBF
      overexpression in NIH3T3 cells leads to a proportionate increase in the
      activities of both reporter and endogenous ribosomal genes. Further, co
      expression of UBF antisense RNA suppresses reporter gene expression. Thus, UBF is
      limiting for ribosomal transcription in vivo and represents a potential
      endogenous ribosomal gene regulator. In contrast to some in vitro studies, in
      vivo, the mammalian and Xenopus forms of UBF1 show an equal ability to activate a
      mouse RPI promoter. This activity is severely impaired in mutants compromised for
      either dimerization or DNA binding. Similarly, the natural UBF2 splice variant
      shows a severely impaired capacity to activate RPI transcription. The data
      strongly suggest that UBF predominantly regulates ribosomal transcription by
      binding to and activating the ribosomal genes, but does not eliminate a possible
      secondary role in titrating ribosomal gene repressors such as Rb. Consistent with
      the DNA folding ability and cellular abundance of the UBF, we suggest that the
      protein may regulate a structural transition between the potentially active and
      active chromatin states.

PMID- 9927758
TI  - Detailed chromosomal and molecular genetic analysis of single cells by whole
      genome amplification and comparative genomic hybridisation.
AB  - Molecular genetic analysis of isolated single cells and other minute DNA samples
      is limited because there is insufficient DNA to perform more than one independent
      PCR amplification. One solution to this problem is to first amplify the entire
      genome, thus providing enough DNA for numerous subsequent PCRs. In this study we
      have investigated four different methods of whole genome amplification performed
      on single cells, and have identified a protocol that generates sufficient
      quantities of DNA for comparative genomic hybridisation (CGH) as well as more
      than 90 independent amplification reactions. Thus, numerous specific loci and the
      copy number of every chromosome can be assessed in a single cell. We report here
      the first reliable application of CGH to single cells from human preimplantation
      embryos (blastomeres) and to single fibroblasts, buccal cells and amniocytes.

PMID- 9927759
TI  - A new signal sequence trap using alkaline phosphatase as a reporter.
AB  - Secreted and transmembrane proteins are critical to the cell-cell interactions
      governing normal development and carcinogenesis. To facilitate the identification
      of such molecules, we have developed a novel signal sequence trap that uses human
      placental alkaline phosphatase as a reporter. Libraries from mouse prostate and
      human prostatic carcinoma were constructed to test the PST (peptide signal trap)
      system, resulting in the identification of several secreted and transmembrane
      proteins.

PMID- 9927760
TI  - Synthesis and applications for unnatural sugar nucleotides.
AB  - The synthesis and biological evaluation of carbohydrate mimetics has begun to
      more clearly define the diverse roles of carbohydrates in nature. Often the
      strategy invoves the design and synthesis of glycosyltransferase and glycosidase
      inhibitors both as tools to elucidate the mechanism of action of these enzymes
      and as potential therapeutic agents. An array of unnatural sugar nucleotides have
      found utility in chemo-enzymatic synthesis. The regio- and stereoselective
      transfer of sugars by glycosyltransferases such as b1,4-galactosyltransferase,
      a1,3-fucosyltransferase, a2,3- and a2, 6-sialyltransferases and N
      acethylglucosaminyltransferase V has demonstrated the broad application of this
      approach. This review summarizes the specificity of these well-studied
      glycosyltransferases for both unnatural sugar donors and acceptors. This
      information combined with the knowledge of the mechanism of action of those
      enzymes is valuable in the design of potent selective glycosyltransferase
      inhibitors and the chemo-enzymatic synthesis of novel carbohydrate mimetics.

PMID- 9927762
TI  - [Current status of pediatric endoscopic surgery].

PMID- 9927761
TI  - Human milk glycoconjugates that inhibit pathogens.
AB  - Breast-fed infants have lower incidence of diarrhea, respiratory disease, and
      otitis media. The protection by human milk has long been attributed to the
      presence of secretory IgA. However, human milk contains large numbers and amounts
      of complex carbohydrates, including glycoproteins, glycolipids,
      glycosaminoglycans, mucins, and especially oligosaccharides. The oligosaccharides
      comprise the third most abundant solid constituent of human milk, and contain a
      myriad of structures. Complex carbohydrate moieties of glycoconjugates and
      oligosaccharides are synthesized by the many glycosyltransferases in the mammary
      gland; those with homology to cell surface glycoconjugate pathogen receptors may
      inhibit pathogen binding, thereby protecting the nursing infant. Several examples
      are reviewed: A fucosyloligosaccharide inhibits the diarrheagenic effect of
      stable toxin of Escherichia coli. A different fucosyloligosaccharide inhibits
      infection by Campylobacter jejuni. Binding of Streptococcus pneumoniae and of
      enteropathogenic E. coli to their respective receptors is inhibited by human milk
      oligosaccharides. The 46-kD glycoprotein, lactadherin, inhibits rotavirus binding
      and infectivity. Low levels of lactadherin in human milk are associated with a
      higher incidence of symptomatic rotavirus in breast-fed infants. A mannosylated
      glycopeptide inhibits binding by enterohemorrhagic E. coli. A glycosaminoglycan
      inhibits binding of gp120 to CD4, the first step in HIV infection. Human milk
      mucin inhibits binding by S-fimbriated E. coli. The ganglioside, GM1, reduces
      diarrhea production by cholera toxin and labile toxin of E. coli. The neutral
      glycosphingolipid, Gb3, binds to Shigatoxin. Thus, many complex carbohydrates of
      human milk may be novel antipathogenic agents, and the milk glycoconjugates and
      oligosaccharides may be a major source of protection for breastfeeding infants.

PMID- 9927763
TI  - [Urinary obstruction in fetal rabbits. An experimental model].
AB  - An original model of urethral ligation on 23 gestational-day fetal rabbits is
      described, that can be applied in studies of both urinary obstruction and
      oligohydramnios. The surgical technique is detailed and subsequent urinary
      obstruction is assessed, as well as the lung weight. In conclusion, this is an
      easy, mildly aggressive, inexpensive and fast model that can be used to
      investigate the pathophysiology of urinary obstruction and that of
      oligohydramnios.

PMID- 9927764
TI  - [Model of bibliometric analysis of publications on pediatric surgery: 1984-1996].
AB  - BACKGROUND: There is no detailed information on the scientific production in
      Pediatric Surgery (PS) in Spain, and we studied this problem by means of a model
      of bibliometric analysis. MATERIALS AND METHODS: Retrospective study of all the
      articles published in the main pediatric Spanish journal (Anales Espanoles de
      Pediadria) over a 13-year period (1984-1996). Quantitative and qualitative
      bibliometric indicators of the articles over PS were performed, and we studied
      also the main differences found between the period before (1984-87) and after
      (1988-96) the foundation of the journal Cirugia Pediatrica. RESULTS: PS is the
      subject matter in 7.6% (n = 227) of all the articles published in this pediatric
      journal. The main type of articles in PS were Clinical Notes (56.9%) and
      Originals (31.7%). The autonomous regions of Madrid, Cataluna, Valencia,
      Andalucia and Pais Vasco have the 70.4% of the total productivity in PS, and we
      also emphasize the relative productivity of others autonomous regions (mainly
      Extremadura). The essential authorship of the scientific activity in PS falls on
      hospitals, with no authorship on University and Health Care Centers. The two
      different bibliometric indicators in PS in relation to the other pediatric
      subspecialties are: the low statistical accessibility and the excessive use of
      English references, with a very low insularity index. After the foundation the
      journal Cirugia Pediaatrica, a reduction in the number of articles over PS
      (mainly Originals) published in Anales Espanoles de Pediatria is noted.
      CONCLUSIONS: PS have a significant quantitative importance in pediatric journals,
      with two negative differences in relation to the other pediatric subspecialties:
      low statistical accessibility and low insularity index. We think is important to
      increase the citation of Spanish publications and, specifically, articles at the
      journal Cirugia Pediatrica.

PMID- 9927765
TI  - [Intraoperative transfusion in pediatric surgery].
AB  - PURPOSE: To analyze the likelihood of perioperative transfusion using the data of
      the abstracted patient discharge records. MATERIAL AND METHODS: It was studied
      the data of the records of the pediatric patients in whom were done surgical
      procedures for 1996. The abstracted patient discharge records are codified
      according the ICD-9-CM codes. RESULTS: 1,166 pediatric patients were operated, of
      whom were transfused 25 (2.1%). The transfusion rate was higher in patients less
      than 3 years old, who were operated with three o more surgical procedures
      simultaneously, who were admitted newly after the admittance here studied, and
      patients operated of spine, dorsolumbar spine, pharynx, thorax and mediastinum,
      central nervous system, colon, vessels and hip. CONCLUSIONS: Given the
      variability of the transfusion rate, to know it will allow a better planning of
      the surgical transfusions, the policy of the hospital blood bank and to increase
      the information to patient about the risk of the elective surgery.

PMID- 9927766
TI  - [Pediatric trauma registry: analysis of 1200 cases].
AB  - OBJECTIVES: We developed the first Spanish Pediatric Trauma Registry in order to
      collect and evaluate information concerning aspects of injuries in our pediatric
      population. METHODS: From January'95 to September'97, 28,713 children younger
      than 16 years were treated in our Hospital for acute injury: 1,200 were admitted
      and included in our database. Our file-registry consists of 108 data points
      including: patient identification, type, place and mechanism of injury, pre
      hospital care, transport, assessment on admission, severity scores, diagnostic
      studies, injuries, treatments and morbidity-mortality. RESULTS: Accidents were
      more frequent in males (69%) than in females. The age-group predominantly was 12
      15 years old (34%). Accidents were more frequent in the street (35.3%) than at
      home (18.7%) or school (14%). Falls and traffic-related accidents were the
      leading cause of injury (38 and 21.1%, respectively). The 16.7% of cases had
      Pediatric Trauma Score < or = 8 (n = 201). The 3.6% of this sustained multiple
      trauma (43 cases with Injury Severity Score > or = 15). Musculoskeletal and head
      trauma was the most frequent (62 and 42.3%, respectively). Surgical or orthopedic
      procedures were performed in 678 patients (56.5%). Average length of stay were
      4.8 days (range 1-93 days), and functional impairments at discharge were found in
      33.9% of patients older than 3 years (n = 338). Mortality rate in our series was
      0.5% (n = 6), and 13.9% in children with ISS > or = 15. CONCLUSIONS: The utility
      of this Registry is to know the epidemiology of our injured pediatric population,
      to review patient care, to develop prevention programs and to compare results
      with other centers so potential deficiencies can be identified and corrected.

PMID- 9927767
TI  - [Analysis of surgical activity of residents in pediatric surgery].
AB  - In the last years we have experienced a remarkable growth of the Credited
      Educational Units in Pediatric Surgery. However any methodological system is not
      applied that evaluated qualitative and quantitatively the efficiency of these
      Units, neither the formative results of the residents. From the mark of the
      European Community a program is designed for the first time that includes, among
      other sections, the residents book ("log-book"). This initiative channeled
      through the National Commission of the specialty has allowed to know in a
      homogeneous and detailed way the activity of the residents in Pediatric Surgery.
      The objective of this work is to analyze the surgical activity developed by the
      Spanish residents of Pediatric Surgery through the book of residents. All the
      gathered data of the books of residents were reviewed differentiating the
      surgical activity in the following ones remote: total surgical activity, neonatal
      surgery, pediatric general surgery, urology, plastic surgery, tumors and thoracic
      surgery. This type of studies allows to guide to the National Commission and the
      Spanish Society of Pediatric Surgery about the quality of the formation of the
      residents, the national necessities, the appropriate number of the credited Units
      and on the selection-evaluation approaches.

PMID- 9927768
TI  - [Deferred appendectomy in a case of appendiceal mass].
AB  - The treatment of acute appendicitis when appendix is technically impossible to
      remove, remains controversial. The clinical case of a 12-years-old child
      diagnosed of acute appendicitis in which appendectomy was not initially
      performable is presently described. After treatment with antibiotics, he was
      submitted to appendectomy five months later. Operative and pathologic findings in
      this second laparotomy prove the predisposition of the patient to a second acute
      appendicitis, and uphold the preventive attitude, the interval appendectomy.

PMID- 9927769
TI  - [Abdominal cystic lymphangioma].
AB  - The cystic lymphangioma is a benign slow-growing tumor derived of the lymphatic
      vessels. It is presented with more frequency in the childhood and the great
      majority are diagnosed under 5 years of life. The most frequent localization is
      in head and neck, although they can be developed in any organ or soft tissue. The
      intraabdominal presentation is not very frequent (2-8%). The clinical
      presentation is very variable being the most frequent sign the appearance of an
      effect mass. The diagnosis of suspicion is radiological by means of abdominal
      ultrasonography and computed tomography. The treatment is surgical. The
      definitive diagnosis is always histologic. They can recidive. We present two
      abdominal cases that illustrate this pathology type.

PMID- 9927770
TI  - [Clinical impact of insulin resistance and relationship with diabetes mellitus
      prevention].

PMID- 9927771
TI  - [Diagnostic usefulness of bronchoalveolar lavage in nosocomial pneumonia
      associated with mechanical ventilation in patients undergoing antibiotic
      treatment].
AB  - We evaluated the diagnostic utility of the colony forming units (CFU) count in
      bronchoalveolar lavage (BAL) cultures from patients with nosocomial pneumonia
      associated with mechanical ventilation (PAMV) and treatment with systemic
      antibiotics. Cultures with greater than 10(4) CFU/ml were considered positive,
      while the absence of cultures was considered negative. Cultures with < or = 10(3)
      CFU/ml were classified as contaminated. The gold standard was defined by
      clinical, bacteriological, and histological criteria. We studied 12 patients
      suspected of having PAMV, and six controls who had no evidence of pneumonia or
      infection of any kind. Positive cultures were found in all patients suspected of
      having PAVM, while all controls had negative cultures. One patient was eliminated
      because we were unable to corroborate the final diagnosis. Using the gold
      standard, nine patients had PAVM, and eight did not have PAVM. The sensitivity of
      the test was 100%, and the specificity was 75%, while the positive predictive
      value was 88%, and the negative predictive value 100%. We conclude that the CFU
      count in BAL cultures is a useful method for the diagnosis of PAMV in patients
      treated with systemic antibiotics.

PMID- 9927772
TI  - [Effect of metoprolol on ventricular relaxation in experimental myocardial
      infarction].
AB  - During the initial phases of myocardial infarction the relaxation ventricular
      time increases. To assess the effect of metoprolol, a beta-blocker agent, on
      constant T, an index derived from left ventricular pressure during the isovolumic
      relaxation phase, 12 mongrel dogs underwent surgical ligation of the anterior
      descending coronary artery. Constant T, diastolic ventricular pressure, heart
      rate and mean arterial pressure were measured at control and after 15, 30, 60,
      120 and 180 minutes after arterial occlusion. Six dogs were used as controls
      while the other six received 35 mg/kg/min of methoprolol, infused during 5
      minutes. Untreated dogs had longer T times, higher ventricular filling pressures
      and hypotension at the end of the study in comparison with the treated does, who
      maintained diastolic function and did not show important changes of arterial
      pressure. The beta-blocker decreased the abnormality of relaxation time and
      preserved ventricular filling and systemic pressures in this model of
      experimental infarction.

PMID- 9927773
TI  - [Acute correction of nocturnal hypoxemia and sleep pattern using continuous nasal
      positive pressure in patients with obstructive sleep apnea syndrome].
AB  - In order to find out the effectiveness of the nasal CPAP in the treatment of
      obstructive sleep apnea (OSA), we studied 30 patients with this diagnosis
      corroborated by nocturnal polysomnography. The average age was 46.37 +/- 11.58
      years, 97% were males and 90% were overweight, with a weight of 101.24 +/- 15.57
      Kg. All the patients were evaluated before and after the application of nasal
      CPAP with a pressure of 12.9 +/- 4.35 cm of H2O with a FIO2 of 21%. The sleep
      efficiency index improved from 0.62 +/- 0.03 to 0.84 +/- 0.02 (p < 0.0001). The
      maximum duration of the apneas diminished from 65.5 +/- 6.5 seconds to 19 +/- 3.7
      seconds (p < 0.0001), and the minimum level of O2 saturation of the hemoglobin
      increased from 56.8 +/- 3.2% to 84.9 +/- 1.9% (p < 00.0001). These findings
      showed a clear improvement in the majority of the evaluated parameters in all of
      the patients, and, in many of them, a normalization. We conclude that the nasal
      CPAP is effective for the acute improvement of the disorders observed during the
      sleep in patients with OSA, which supports its therapeutic use in this illness.

PMID- 9927774
TI  - [Reintervention to complete the surgical treatment of thyroid cancer. Indications
      and histopathological findings].
AB  - In Mexico, 39% of 158 patients operated on for thyroid cancer require reoperative
      thyroid surgery. We retrospectively reviewed the indications and
      histopathological findings of 60 patients reoperated on because of: a) suspected
      persistent or recurrent disease; b) high risk patients treated by lobectomy; c)
      different histology; d) complete lack of information, e) and distant metastasis.
      In 53 cases (88%), the initial surgery was nodulectomy or lobectomy, and in seven
      (11%) was subtotal or near-total thyroidectomy. Among the 60 reoperations, 50
      were completion total thyroidectomy and 10 were near-total thyroidectomy. In 27
      cases (45%) a neck dissection was additionally done. Histologic examination
      revealed thyroid carcinoma in 32 cases (53%) and neck node metastasis in 28 cases
      (47%). Complications included six cases (9%) of permanent palsy of the recurrent
      laryngeal nerve after the initial surgery outside of our hospital and two cases
      (1.75%) of reoperated cases. In four reoperated patients (6.6%), permanent
      hypoparathyroidism was developed. It is mandatory to complete thyroidectomy and
      neck dissection in a high proportion of patients initially treated in general
      hospitals due to an inadequate criteria in the selection of the extension of
      thyroidectomy and treatment of neck node metastases. Histologic findings of these
      patients support our indications to complete the surgical treatment.

PMID- 9927775
TI  - [Cellular and molecular mechanisms of neurodegeneration].

PMID- 9927776
TI  - [Aminoglycosides, their ototoxic effect].
AB  - The aminoglycosides are broad-spectrum antibiotics especially effective against
      many strains of gramnegative bacteria. Since streptomycin was used for
      tuberculosis treatment, the toxic side effects of such antibiotics were
      identified. The kidney and the inner ear are affected. The nephrotoxicity is
      usually reversible, while the chronic ototoxicity is irreversible. Within the
      inner ear, it is the cochlear and vestibular sensory epithelium that is damaged.
      A toxic mechanism in which an interference with mitochondrial protein synthesis
      is central has been inferred. During the last fifty years, risk factors for
      aminoglycoside-induced-ototoxicity have been identified, including a genetically
      transmitted hypersensitivity to the ototoxic effect. Although several strategies
      to prevent the damage have been proposed, today it is not rare that patients
      suffer permanent loss of hearing and loss of balance due to aminoglycoside
      toxicity. This review gives a brief background of aminoglycoside ototoxicity,
      some strategies to prevent it, and the therapeutic use of the vestibulo-toxic
      effect.

PMID- 9927777
TI  - [Physicians and surgeons during the French intervention and the Second Empire].
AB  - Because of the law of July 17th, suspending the payment of the national and
      foreign debt, England, Spain and France, the main creditors of Mexico, determined
      to perform a military expedition in order to sustain their claims. Allied armies
      reached the Mexican shores on December 1861 and January 1862, when the cause of
      conflict was already inexistent. In fact, the said law was abrogated on November
      23rd. In accordance with the settlement of La Soledad, while English forces
      remained near the coast, Spanish and French soldiers transiently settled in
      Orizaba and Tehuacan, respectively. Their military physicians assisted the
      wounded and mutilated Mexican people consequently to disaster of San Andres
      Chalchicomula (March, 1862). When the French army initiated hostilities against
      the Mexican forces, the physicians and surgeons of both sides excelled for their
      abnegation and sacrifice spirit in the battle of May 5th, as well as during the
      Puebla' siege. There were also combatant physicians and surgeons, who
      participated in several episodes of war. On the other hand, French military and
      Mexican civil physicians constituted, on April 1864, the original nucleus of our
      Academy of Medicine. Physicians continued being loyal to their mission at the
      time of the second empire, excelling particularly during the siege of Queretaro
      by the republican forces. In spite of the inevitable ravages of the war, at that
      unfortunate time unquestionable advances in the field of the scientific progress
      and of the human solidarity, were attained.

PMID- 9927778
TI  - [Medicine and surgery books printed in New Spain and their authors in the first
      two centuries of colonial culture (1570-1692). Part II].

PMID- 9927779
TI  - [The first operating room in Mexico and one of the first in the world (1876)].

PMID- 9927780
TI  - [Radiologic lymphography of the human heart by doctor Alejandro Celis and
      collaborators].

PMID- 9927781
TI  - [Centrofacial lymphoma, cause of middle line granuloma syndrome. Report of a
      case].
AB  - The male patient is in his fifth decade with a history of four months with right
      nasal obstruction, hematopurulent rhinorrea and scabs in the nose. The initial
      physical examination showed necrotic tissue and scabs in both the nasal foci.
      Three months later he presented a septal perforation and eroded necrotic injury
      in the hard palate. The two initial biopsies that were carried out showed chronic
      unspecified inflammation, and the third reported a polymorphic reticulosis. The
      histopathological analysis of the material of the third biopsy showed the
      existence of a non-angiocentric intermediate centrofacial lymphoma. The patient
      was submitted to treatment with simultaneous radiotherapy and chemotherapy with
      the end result of a totally successful remission of the lymphoma. These
      abnormalities usually appear as ulcers and erosions of the cartilage and bones of
      the nose, the paranasal sinuses and the palate. They are polymorphic, and there
      exists evidence of its association with the Ebstein Barr virus. The patient has
      been observed during the last five years and has shown no evidence of recurrence
      of any related of the disease. As a consequence of the sickness, the patient had
      difficulties to talk and eat, but with rehabilitation he now has adequate
      phonation and eating capacity. The immunohistochemistry and molecular genetic
      science branches of medicine have almost solved the diagnostic and therapeutic
      problems related to this sickness. The individual's prognosis depends mainly on
      the extension of the affection and seriousness of the disease from which the
      patient suffers.

PMID- 9927782
TI  - [Nodular pulmonary infiltration in acute lymphoblastic leukemia].

PMID- 9927783
TI  - [In situ polymerase chain reaction. New method for genetic diagnosis].

PMID- 9927784
TI  - [Pharmacoepidemiology in Mexico].

PMID- 9927785
TI  - [Chagas disease or American trypanosomiasis].

PMID- 9927786
TI  - [Legal liability and the professional work of physicians].

PMID- 9927787
TI  - [Biological hypothesis of hope].

PMID- 9927788
TI  - [Risk factors for the development of germ cell tumors in children].

PMID- 9927789
TI  - [Identifying the patient with severe acute pancreatitis].

PMID- 9927790
TI  - ["Risk factors for the development of germ cell tumors in children"].

PMID- 9927792
TI  - [Incidence and clinical features of splenic abscesses, with special reference to
      tuberculous etiology in a general hospital].
AB  - BACKGROUND: The aim of this revision is to know the incidence of splenic abscess
      (SA) in our hospital, its etiology, with special reference to tuberculosis, and
      clinical characteristics. PATIENTS AND METHODS: Abdominal CT-scan performed
      during the period 1987-1997, with the diagnosis of splenic abscess were reviewed.
      Etiologic diagnosis standed on blood or sputum cultures, PAAF and/or histologic
      study of lymph nodes. RESULTS: Seventeen cases of SA were obtained, 12 males and
      5 females. Limits of age: 13 and 77 years. The causal microorganisms were: M.
      tuberculosis (7), Mycobacterium aviumintracellulare (1), S. aureus (2), S.
      anginosus (1), S. milleri (1), E. coli (1), C. albicans (1), T. biguelle (1) and
      polymicrobian flora (1). One case was of unknown etiology. Underlying illnesses
      were: AIDS (7), malignant neoplasms (3), diabetes (2), endocarditis (2), Sjogren
      syndrome (1) and complications of abdominal surgery (2). Clinical presentation in
      nontuberculous splenic abscess was fever and upper-left abdominal pain.
      Predominant symptoms in tuberculous splenic abscess were fever and weight loss.
      Blood cultures were positive in 80% of non tuberculous splenic abscess. Specific
      treatment for tuberculosis improved all patients with tuberculous splenic
      abscess, without needing surgery or corticosteroids. CONCLUSIONS: From the total
      of splenic abscess, 41.1% were tuberculous, six with AIDS and one with Sjogren
      syndrome. Diabetes and malignant neoplasms were the commonest underlying
      illnesses in the non-tuberculous. In these, clinical presentation consisted in
      fever and upper-left abdominal pain. In patients with tuberculous splenic
      abscess, the main complaint was weight loss. A prompt treatment is generally
      succesful.

PMID- 9927791
TI  - [The attitude of primary health care physicians in the metropolitan area of
      Barcelona about the diagnosis and treatment of Helicobacter pylori infection in
      gastroduodenal diseases].
AB  - AIM: To evaluate the attitude of primary health care physicians versus the
      diagnosis and treatment of infection by Helicobacter pylori in patients with
      dyspepsia and gastroduodenal ulcer. DESIGN: An observational, transversal study
      was performed by a self administered questionnaire from June to October, 1997.
      PARTICIPANTS: Primary health care physicians from 38 reformed Medical Centers in
      the metropolitan area of Barcelona were included in the study. RESULTS: Of the
      359 doctors to whom the questionnaire was sent, 283 responded (78.8%). In a
      patient with dyspepsia 95.4% would first request endoscopy. If they knew of the
      presence of infection by Helicobacter pylori 96.1% would administer eradication
      treatment in patients with gastric and duodenal ulcer and 15% would also do so if
      the endoscopy were normal. If the presence of infection by Helicobacter pylori
      were unknown in a patient with gastroduodenal ulcer, 65.3% would treat with anti
      H2 or proton pump inhibitors associated with a diagnostic test of infection by
      Helicobacter pylori. If the physician decided to carry out eradication treatment
      of Helicobacter pylori infection, 98.6% would use one of the regimes recommended
      by different scientific societies. If confirmation of eradication of Helicobacter
      pylori infection were requested, 89% would do so one and three months after
      completion of treatment. In patients with gastric ulcer, 69.3% would request
      endoscopy on completion of treatment. The percentage of physicians specialized in
      Family and Community Medicine who would carry out eradication treatment in
      patients with duodenal ulcer and Helicobacter pylori infection and who would
      request endoscopies in patients with dyspepsia was found to be statistically
      significant in comparison with physicians without this specialty. CONCLUSIONS:
      The attitude of primary care physicians in the metropolitan area of Barcelona
      with regard to the diagnosis and treatment of infection by Helicobacter pylori in
      gastroduodenal diseases largely reflects the recommendations recently made by
      several scientific societies. In general there are no significant differences
      with respect to this attitude in regard to the age and sex of the physician,
      although their training was found to influence in some of the responses analyzed.

PMID- 9927793
TI  - [Pancreatic glucagonoma and deep vein thrombosis].
AB  - Glucagonoma is an endocrine tumor of almost exclusively pancreatic origin which
      is rarely associated with a clinical syndrome mainly characterized by migratory
      necrolytic erythema, hyperglycemia, weight loss, hypoaminoacidemia and anemia.
      Ten to 30% of the patients may present thromboembolic phenomenon, deep vein
      thrombosis and pulmonary embolism which often lead to the death of the patient.
      We report the case of a patient diagnosed with pancreatic glucagonoma the
      presentation of which consisted in episodes of repeated deep vein thrombosis
      without associated migratory necrolytic erythema.

PMID- 9927794
TI  - [Inguinal tumor as the first manifestation of a pancreatic pseudocyst].
AB  - We report a case of pancreatic pseudocyst in alcoholic pancreatitis, that
      presented as a mass in the inguinal region. The mechanism of this peculiar
      clinical presentation was the dissemination of the content of the pseudocyst
      along the psoas muscle. We review the involvement of psoas muscle in pancreatic
      pathology, giving emphasis to reports of inguinal or thigh masses as initial
      manifestations.

PMID- 9927795
TI  - [Spontaneous bacterial peritonitis caused by Listeria monocytogenes].
AB  - We present a 68 year old male with alcoholic cirrhosis that was admitted with
      abdominal pain and fever. Hepatocarcinoma and spontaneous bacterial peritonitis
      by Listeria monocytogenes was diagnosed. The patient was treated with ampicillin
      and tobramycin during 25 days following a favorable course although ascitic fluid
      remained abnormal during 21 days. It is noted the rarity of Listeria as a cause
      of bacterial peritonitis in cirrhotic patients although they are immunodeficient.
      It is also important to establish the etiological origin because standard
      treatment of spontaneous bacterial peritonitis is cefotaxime and Listeria is
      resistant to this antibiotic. The 66% of spontaneous bacterial peritonitis
      secondary to Listeria monocytogenes infection in cirrhotic patients has been
      reported in Spain and this might be due to a higher incidence of human
      listeriosis in this country.

PMID- 9927796
TI  - [Pathology of the ductal plaque].

PMID- 9927797
TI  - [Thrombotic symptoms in inflammatory intestinal disease].

PMID- 9927798
TI  - [Acute hepatitis induced by Ecstasy].

PMID- 9927799
TI  - [Toxic hepatitis caused by flutamide].

PMID- 9927800
TI  - [Melatonin: myth or reality?].

PMID- 9927801
TI  - [Prenatal diagnosis. II. Importance of ultrasonographic markers in prenatal
      diagnosis of chromosome abnormalities].
AB  - The Medical Genetic Unit of the University of Zulia (MGUUZ) has developed a
      Prenatal Diagnosis Program (PDP) since January-1993, in which Genetic Risk
      Factors are determined in couples who request prenatal genetic counseling. In
      this program, different prenatal diagnostic procedures are performed to detect
      congenital defects during intrauterine life. One of these procedures is the Fetal
      Sonogram (FS). FS is a non invasive technique which permits the prenatal
      diagnosis of many genetic dysmorphic syndromes. Through the search of abnormal
      specific characteristics in the fetus, chromosomopathies may be suspected. These
      findings are named "Echosonographic Markers of Chromosomal Abnormalities" (EMCA).
      During three years (January-1993 to December-1996), patients attended in the PDP
      included 321 pregnant women in which 312 FS were performed. Abnormal outcomes
      were 22 (17 with isolated congenital malformations and 5 with EMCA). Only one
      fetus with chromosome abnormality (46,XX21q-) could not be detected by FS. The
      goals of this paper are: 1) to report 5 patients with sonographic markers
      suggestive of chromosomal abnormalities and 2) to show the FS usefulness in
      prenatal diagnosis of chromosompathies. We conclude that, in the search of the
      EMCA the FS should be offered systematically to all pregnant women without
      recognizable genetic risk. They are the main group with optimal reproductive age
      and in consequence, with the possibility of having a relatively major number of
      conception outcomes with congenital defects, with or without chromosomic
      etiology. The majority of those defects can be detected by FS and could allow us
      to select the patients in which the use of an invasive prenatal diagnostic
      procedure could be justified.

PMID- 9927802
TI  - [Diagnosis and management of patients with sex differentiation disorders:
      experience at the Unit of Medical Genetics of the University of Zulia, Maracaibo,
      Venezuela].
AB  - Abnormalities of sexual differentiation (ASD) represent a group of entities,
      heterogeneous in their etiopathogenesis and clinical manifestations. In order to
      characterize and analyze the epidemiologic, clinical, endocrine and genetic
      aspects of patients with ASD consulting UGM-LUZ between 1971-1996, the families
      that had at least one of its members affected were evaluated. Strict diagnostic
      criteria to each entity were applied. Cytogenetic, hormonal, radiological,
      echographic and anatomopathological evaluations were done in each patient. From
      391 families, 429 patient consulted with ASD. They represent 5.4% of the patient
      who consulted to UGM-LUZ in the same period. 214 (50%) patients with definitive
      diagnosis of ASD were identified to fill the established inclusion criteria. The
      distribution was the following: 139 with anomalies of the sexual chromosomes; 36
      with congenital adrenal hyperplasia; 21 with complete androgen insensitivity
      syndrome; 14 with mixed gonadal dysgenesis; and 4 with true hermaphroditism. 183
      (42.7%) patients with male pseudohermaphroditism and 17 (3.9%) with female
      pseudohermaphroditism were diagnosed as they did not fulfill the established
      diagnostic criteria. 15 (3.4%) patients presented ASD associated to a
      polymalformative syndrome. The ASD are very complex entities, they need the
      participation of an interdisciplinary team for their diagnosis and management
      process.

PMID- 9927803
TI  - [An ultrastructural evaluation of Pneumocystis carinii].
AB  - The pneumocystis carinii (PNC) is a challenge, because its taxonomy has not been
      completely explained. PNC seems to be a chimera with fungal and parasitic
      characteristics. The objective of the present study is to analyze the different
      stages observed in PNC using transmission electron microscopy in order to
      correlate them with bibliographic reports regarding a possible taxonomic
      classification. The trophic stage was the form most frequently encountered in
      alveolar spaces and their organisms varying in size and shape from 6 to 20
      microns. Cyst were round or oval, with diameters ranging between 4 and 12
      microns, showing four intracystic bodies were individually limited by a membrane.
      Connections between the membrane of intracystic bodies and junctions between them
      and the inner cell membrane of the cyst wall were also observed. Our
      ultrastructural findings appear to be in agreement with several reports which
      considered PNC among the fungi, most likely related them to the non-gemating
      Ascomycetes.

PMID- 9927804
TI  - [How to reduce the prevalence of HIV-positive blood donors].
AB  - Despite abolishing the policy of giving the results of the serological test as a
      way to promote blood donation, and also after improving the predonation
      questionnaire, we still have a high prevalence of HIV positive blood donors. In
      this paper we try to analyze, interviewing the HIV positive blood donors in our
      Counselling Clinic from January 1995 to December 1996, why they were accepted. We
      asked the HIV positive blood donors to fill a form with the following questions:
      identification, kind and frequency of blood donation, HIV high risk behaviour,
      awareness of predonation serological status, willingness toward blood donation,
      awareness of how dangerous the transfusion of HIV contaminated blood is. For the
      screening we used Abbott HIV1/HIV 3rd generation plus EIA, test and HIV-1 Western
      Blot Cambridge, Biotest, Worcester MA, for confirmatory assays. During the
      evaluation period, 53,338 blood donors were attended, 130 (0.24%) were confirmed
      HIV positive. Only 18/130 (13.84%) assisted to the Counselling Clinic. The mean
      age was 33.27 +/- 5.35 years old, all males, 15 singles and 3 with stable
      couples. 6/18 (33.33%) could have been discarded because of physical appearance
      or because of theirs jobs. "Voluntary Donation" was higher than in the control
      group (p = 0.0001). Homo/bisexual and promiscuous behaviour (p = 0.0003) were the
      predominant high risk factors, in this group 55.55% had more than one risk
      factor. The association with HBV and syphilis was high (p = 0.0001 and p =
      0.0005). 5/18 (27.77%) knew they were HIV positive; 3/18 (16.66%) had the
      suspicion they were HIV positive and 10/18 (55.55%) did not know it; however the
      risk factors were the same in those groups. In the knew/suspicion group the main
      reasons for blood donation were: Performing the test once more, 6; failure in the
      predonation questionnaire, 1; family pressure, 1. In the group that ignored their
      HIV positivity: ignorance of belonging to a high-risk group, 6; lack of
      confidence in the interviewer, 3 and failure in the predonation questionnaire, 1.
      61.11% knew that the HIV tests were performed on all blood donations and the the
      positive ones were discarded. No one had knowledge of the window period.
      CONCLUSIONS: 1. It is necessary to spread more information to the general
      population about the ways of HIV transmission, the risk factors and its
      prevention. 2. To make aware all HIV positive or those that suspect they are the
      HIV positive how dangerous their blood donation could be. 3. Offering the general
      population a free HIV test and giving the appropriate counselling and support. 4.
      Improving the questionnaire, assuring that the blood donor could understand the
      real meaning of the questions and how important his/her truthfulness is. 5. To
      consider the implementation of the p24 antigen test as mandatory to all blood
      donations and all the new techniques to avoid HIV transmission. 6. To change the
      "related" blood donors to the true voluntary, altruistic, blood donor.

PMID- 9927805
TI  - [Molecular bases of the programmed cell death process: implications of tumor
      suppressor protein p53 and other proteins in the control of cell cycle.
      Mechanisms of apoptotic action. Review].
AB  - Apoptosis is a mechanism of cell death that occurs in normal development and on
      the regulation of vertebrate tissues and organ cellularity. Neurons undergo p53
      dependent and p53-independent apoptosis, depending upon the stimulus that
      triggers DNA fragmentation. Many neurons in the developing nervous system suffer
      apoptosis, with the cyclin D1 being an essential mediator of neuronal cell death.
      Other characteristics of apoptosis are: condensation of the nucleus,
      fragmentation of chromatin at nucleosome linkage sites, membrane blebbing, and
      the formation of apoptotic bodies. Among the possible molecular mechanisms are:
      (a) activation of proteases, as ICE (Il-1 beta converting enzyme); (b) calpain is
      activated in several cells, with PARP (Poly-ADP-ribose polymerase) and a small U1
      Ribonucleoprotein, being substrates for ICE and its homologs such as ICH and
      others proteins. The p53 gene encodes a transcription factor that contributes to
      several different cellular activities, including apoptosis, the cellular response
      to radiation, and the activation of proteins such as GADD, Bcl-2 (represses to
      apoptosis) and Bax. P53 exerts a role as inductor of apoptosis by transactivating
      expression of the Bax gene. The p53 gene tumor suppressor limits cellular
      proliferation by including either the arrest of cell cycle in G1, or apoptosis,
      depending on the cellular context. The p21 is an inhibitor of cyclin-dependent
      kinase, which is transactivated by p53. During apoptosis, there is an activation
      of both, c-myc, and the transcription factor NF-kB, which is a important
      regulator of apoptosis. As an example of signalization of apoptosis we have
      selected to illustrate the problem related to the system Fas/APO in thymocytes.

PMID- 9927806
TI  - Dimensions and process of stigmatization in leprosy.
AB  - Leprosy is a disease which has struck fear into human beings for thousands of
      years. This is partly because it causes considerable deformities and
      disabilities. In 1991, the 44th World Health Assembly adopted a resolution to
      eliminate the disease as a public health problem by the year 2000. However, one
      of the major obstacles to achieving this objective is the stigma associated with
      the disease. Stigma against leprosy patients affects all aspects of leprosy
      control. This paper describes a model of the stigmatization process in leprosy.
      The process of stigmatization can be divided into two stages. The first stage
      describes how certain cognitive dimensions of leprosy lead to a variety of
      affective responses towards the disease. The second stage involves how these
      affective responses contribute to social devaluation of the leprosy patient and
      consequently, the adoption of negative behaviours towards them.

PMID- 9927807
TI  - Histological studies in primary neuritic leprosy: changes in the apparently
      normal skin.
AB  - The visually normal skin of 196 patients diagnosed clinically to have primary
      neuritic leprosy was studied histologically to determine whether there were any
      specific changes due to the disease in this site. Histological changes due to
      leprosy were seen in 32.1% of the patients, and included, indeterminate leprosy
      in 19.4%, borderline tuberculoid leprosy in 6.6% and borderline lepromatous
      leprosy in 6.1%. The remaining biopsies showed mild non-specific dermal
      inflammation, mild nerve changes or no significant lesion. The nerve inflammation
      and/or granulomas were mostly in the deep dermal nerves or neurovascular
      complexes. This study shows that there is a cutaneous component to primary
      neuritic leprosy and the disease is not totally confined to nerves. The absence
      of visible hypopigmented patches in these patients is probably related to the
      deep location of the dermal inflammation.

PMID- 9927808
TI  - Histological studies in primary neuritic leprosy: changes in the nasal mucosa.
AB  - The nasal mucosae of 39 cases of primary neuritic leprosy (PNL) registered at
      Karigiri were studied histologically to determine nasal mucosal involvement in
      PNL and its relevance to the pathogenesis of the disease. Specific changes of
      leprosy were seen in 20 (51%) biopsies, ranging from macrophage granulomas with
      acid fast bacilli, to epithelioid granulomas and nerve inflammation. The
      remaining biopsies revealed chronic inflammatory changes of the mucosa or mild
      non-specific nerve changes. These findings show that there are widespread effects
      of the disease even in PNL patients in whom the disease is believed to be
      confined to the peripheral nerves. The findings also show that early leprosy
      involvement can be found in the nasal mucosa even before lesions become apparent
      in the skin or other parts of the body. The nasal mucosa could be one of the
      sites for the primary lesion in leprosy. Clinical and histological examination of
      the nasal mucosa may be useful and important in the early diagnosis of leprosy
      and especially in contacts.

PMID- 9927809
TI  - A field trial of detection and treatment of nerve function impairment in leprosy-
      report from national POD pilot project.
AB  - As part of a collaborative project between the Ministry of Health of China (MOH)
      and The Leprosy Mission International (TLMI) on leprosy rehabilitation and
      prevention of disability (POD), a total of 1407 patients was monitored for
      possible nerve function impairment (NFI) through standardized clinical nerve
      function assessment between May 1995 and February 1998. Of these, 191 patients
      were found to have NFI and were put on a fixed regimen of prednisolone. In this
      study, 36.7% of NFI occurred before diagnosis of leprosy, 35.6% developed during
      MDT and 25.7% after their release from MDT. Overall, 7.5% (105 out of 1407) of
      all patients, or 55.9% of patients with NFI, suffered from silent neuropathy. Of
      the affected nerves, 62.6% had silent neuropathy. Sensory impairment responded to
      prednisolone satisfactorily, giving a recovery rate of 73.8%, 76.5% and 81.0% in
      ulnar, median and posterior tibial nerve, respectively. Sensibility in patients
      even with a NFI duration longer than 6 months made significant improvement (p <
      0.05). Motor function improvement was less satisfactory, especially in ulnar and
      c. popliteal nerve. The possible reasons are analysed. Our findings with regard
      to sensibility changes confirm that once it becomes clinically detectable, NFI is
      no longer at the 'early' stage. More sensitive tests are necessary to detect real
      'early' sensory impairment in the field. Our study also indicates that with well
      trained field staff and proper equipment for nerve function assessment, early
      detection and treatment of NFI can be practical and effective.

PMID- 9927810
TI  - beta 2-Glycoprotein I-dependence of anticardiolipin antibodies in multibacillary
      leprosy patients.
AB  - This study was undertaken to investigate the influence of beta 2-glycoprotein I
      (GPI) on anticardiolipin antibody (aCL) titration in leprosy. The study group
      consisted of 140 sera from patients with multibacillary leprosy (46 borderline,
      94 lepromatous). The group included newly diagnosed, previously untreated
      patients, patients under treatment and patients released from treatment. GPI
      addition enhanced significantly the aCL titres in sera from lepromatous leprosy
      but not in those from borderline leprosy. Moreover, when the patients were
      classified according to their bacteriological status, aCL titres were found to be
      significantly higher in skin smear positive patients compared to
      bacteriologically negative patients. Thus, the present study demonstrates that
      aCL in multibacillary leprosy patients are mainly of the GPI-dependent type and
      emphasizes the importance of GPI addition for aCL titration in leprosy.

PMID- 9927811
TI  - Explanatory models and help-seeking behaviour of leprosy patients in Adamawa
      State, Nigeria.
AB  - In northern Nigeria 60 leprosy patients, 49 outpatients and 11 in-patients, were
      interviewed about their help-seeking behaviour and explanatory models before
      their first contact with the leprosy services. Most patients showed a delay of
      more than 1 year. After leprosy was provisionally diagnosed by lay persons, 27%
      of patients found their way to the leprosy services within 3 months. Chemists
      (popular sector) and the professional sector frequently missed the diagnosis. If
      early case finding is to be improved, it is important to involve them in case
      finding activities and to train them in adequate diagnostic skills. No
      significant correlations were found between total delay and sex, age, religion or
      leprosy classification, except with visible deformity at the time of the
      interview and illiteracy. Consultation of folk healers was the major reason for
      delay. Most patients consulted folk healers, who, although they claimed to have a
      positive attitude towards modern medicine in the case of leprosy, never referred
      patients to the leprosy services. While many patients held a variety of causes
      responsible for leprosy, most patients explained the disease in traditional terms
      (58%), while only a minority used modern concepts (20%). This emphasizes the need
      for continuous attention for health education of diagnosed patients and their
      families. No significant difference was found between male and female patients
      concerning their concept of leprosy. Denial of the leprosy diagnosis was rare.

PMID- 9927812
TI  - Surgery of common paralytic conditions.

PMID- 9927813
TI  - Fixed drug eruption due to rifampin.
AB  - A case of fixed drug eruption due to rifampin in a leprosy patient is described.
      Fixed drug eruption due to rifampin with the classical residual hyperpigmentation
      has not been described before.

PMID- 9927814
TI  - Skin patches heralding relapse in a treated case of neuritic leprosy.

PMID- 9927815
TI  - Comment: leprosy, HIV infection and lepra reactions.

PMID- 9927816
TI  - ["Bronchial asthma--therapeutic advances due to leukotriene antagonists."
      Symposium: "Leukotriene antagonists: a therapeutic advance in the control of
      asthma." 30-31 October 1998, Copenhagen].

PMID- 9927817
TI  - [Glomerulonephritis associated with hepatitis c virus infection].
AB  - We report 4 patients with glomerulonephritis (GN) associated with hepatitis C
      virus (HCV) infection seen between August 1993 and July 1996. Two of them were
      male and median age was 41 years. Anti-HCV was detected by enzyme-immunoassay and
      HCV-RNA by PCR. Serum cryoglobulins, 24-hour proteinuria, and erythrocyte
      dismorphism were also determined. Viremia, cryoglobulinemia, hematuria and
      proteinuria were observed in all patients. Liver biopsies revealed inflammatory
      activity in 3 cases, and renal biopsies revealed membranoproliferative
      glomerulonephritis in 3 patients and mesangial proliferative glomerulonephritis
      in 1 patient. Two patients are on specific therapy for HCV infection (IFN in
      combination with ribavirin) and have presented clinical and laboratory
      improvement. The occurrence of active liver disease and viremia concurrent with
      urinary alterations suggests viral involvement in renal disease, a conclusion
      supported by the by improvement of urinary alterations observed after treatment
      for HCV. We conclude that the search for viral markers in patients with GN is
      important since their detection could change the therapeutic approach.

PMID- 9927818
TI  - [Therapeutic evaluation of artesunate in experimental Schistosoma mansoni
      infection].
AB  - Mice experimentally infected with Schistosoma mansoni were treated orally with
      artesunate (Lactab) in a single dose of 300 or 500 mg/kg or over a period of five
      consecutive days. The animals were sacrificed 7, 30, 60 or 90 days after
      treatment. Statistically significant differences were found in the distribution
      and mortality of the worms and in the alterations of the oogram in the treated
      group when compared to control in all of the tested schemes when the animals were
      sacrificed 30 days after treatment. Morphological analysis of female worms showed
      a reduction of ovarian volume and rarefaction of the vitelline follicles. These
      modifications were more marked after treatment with the higher dose, explaining
      the alteration of the oogram which reached 100%. However, when the animals were
      sacrificed 60 or 90 days after treatment, the differences and alterations were
      smaller, showing that the surviving worms recovered and restarted oviposition.

PMID- 9927819
TI  - [Human leptospirosis outbreak in the district of Ciego de Avila, Cuba].
AB  - Forty leptospirosis outbreaks occurred in Ciego de Avila province from 1980 to
      1995. The main events involved in the outbreaks were floods, bathing in rivers
      and activities related to sugar cane and banana cultivation. The number of cases
      increased after June, with higher incidences reported in October and November.
      The most affected age groups were 10-14 years, 15-19 years and 30-34 years. Men
      were more affected than women. Students, people residing in the urban zone and
      farmers were the most affected groups. A total of 21 outbreaks out of 40 were
      confirmed by the microagglutination test and the remaining 19 by the hemolytic
      test. Pomona and Australis were the serogroups most frequently detected by
      microagglutination.

PMID- 9927820
TI  - Influence of canine brain decomposition on laboratory diagnosis of rabies.
AB  - Canine brains infected with rabies virus were submitted to decomposition by being
      left at room temperature of 25 to 29 degrees C for up to 168 h. At 24 h
      intervals, brain fragments were analyzed by immunofluorescence (IF) and by the
      mouse intracerebral inoculation (MI) test to confirm the diagnosis of rabies and
      to measure the putrefaction effect on the accuracy of the diagnosis. Forty eight
      h after the beginning of the experiment, the MI test showed signs of impairment
      with four negative results, while after 72 h, 100% of the results were negative
      to the MI test and only one result was negative to the IF test, indicating that
      the threshold period for accurate diagnosis is 24 to 48 h before putrefaction.
      The authors recommend the shipment of suspected cases of rabies to the laboratory
      for confirmation, but the use of putrid materials for diagnosis is meaningless
      because of false-negative results.

PMID- 9927821
TI  - [Utilization of the waste of sisal industry in the control of mosquito larvae].
AB  - The aim of this research was to utilize the waste residues of sisal fiber
      separation from Agave sisalana leaves to develop a larvicide for the combat of
      mosquito transmitting tropical diseases. Larvae of Aedes aegypti and Culex
      quinquefasciatus were exposed to different concentrations of the Agave extract
      for 24 hours to determine lethal concentrations. The LC50 for A. aegypti was 322
      ppm and the LC50 for C. quinquefasciatus was 183 ppm. To detect the active
      substances, saponins were investigated. It was found that the various components
      of the extract were effective in eliminating the larvae. Under field conditions,
      this formulation can probably be used at 100 ppm, which causes 100% mortality of
      C. quinquefasciatus larvae after 3-4 days. The product is not recommended for use
      against A. aegypti due to the necessity for high concentrations and to the fact
      that the larvae of this species live frequently on drinking water. To avoid
      fermentation, Agave extract should be used in a dehydrated form which also
      represent a good formulation for practical use.

PMID- 9927822
TI  - [Paracoccidioidomycosis in children in Belem, Para].
AB  - During the period from January/85 to July/96, 102 cases of paracoccidioidomycosis
      were observed in a hospital in Belem, PA. Thirteen of these cases were children
      between 3 and 13 years of age, with a predominance of females (8:5). All patients
      presented the disseminated subacute form of the mycosis. The high prevalence of
      the mycosis in children in endemic areas of the Amazon region is discussed.

PMID- 9927823
TI  - [Cardiac neuronal depopulation in hamsters (Mesocricetus auratus) chronically
      infected with Trypanosoma cruzi].
AB  - The aim of this study was to obtain an experimental animal model of destruction
      of cardiac neurons in order to investigate the behavior of the cardiac nervous
      system of hamsters chronically infected with Trypanosoma cruzi. We counted the
      neuronal cells of the cardiac autonomic nervous plexus in hamsters inoculated
      with 35,000 blood forms of three different T. cruzi strains and killed 5, 8 and
      10 months after infection. We showed for the first time severe neuronal
      destruction in an experimental animal model with characteristics similar to those
      observed in human Chagas'disease.

PMID- 9927824
TI  - [Etomidate and vecuronium in induction of anesthesia of chronic Chagas'
      cardiopathy].
AB  - Fifteen chagasic and 26 non-chagasic patients were evaluated for hemodynamic and
      cardiovascular responses during induction of anesthesia with etomidate (a
      hypnotic agent) and Vecuronium (a neuromuscular blocker). Blood for serum testing
      was collected during anesthesia. Blood pressure, heart rate and rhythm, mean
      arterial pressure and arterial oxygen saturation were also monitored on six
      different occasions during anesthesia. When the various stages of anesthesia were
      compared, significant differences in blood pressure and heart rate were observed.
      For any of the given stages of anesthesia blood pressure and heart rate did not
      show significant differences when chagasic were compared to non-chagasic
      patients. Arterial oxygen saturation remained steady in all cases. We conclude
      that both drugs are safe for use during the induction of anesthesia in chronic
      chagasic patients.

PMID- 9927825
TI  - [Clostridium difficile as an inducer of inflammatory diarrhea].
AB  - Clostridium difficile has been pointed out as an important agent of diarrheal
      diseases associated with antibiotic use. However, due to its complexity, the
      physiopathology of these diseases is only partially elucidated, although a series
      of scientific works has demonstrated the importance of toxins A and B in the
      pathogenesis of the inflammatory diarrhea induced by this microorganism. The
      inflammatory mechanisms involved in the biological activities of these toxins are
      complex. There are some studies demonstrating that toxin B has no enterotoxic
      activity in vivo. However, this toxin causes dose-dependent eletrophysiologic and
      morphologic modifications of human colonic mucosa in vitro. In addition, toxin B
      stimulates the synthesis of potent inflammatory mediators by monocytes and
      macrophages. The effects provoked by toxin A on the intestinal mucosa are quite
      evident and are characterized by intense fluid secretion and by inflammatory cell
      accumulation, such as macrophages, mast cells, lymphocytes and neutrophils, with
      the consequent release of mediators such as prostaglandins, leukotrienes,
      platelet activating factor, nitric oxide and cytokines.

PMID- 9927826
TI  - [Splenic abscess caused by Brucella abortus].
AB  - A 23 year-old man with prolonged fever caused by Brucella abortus is reported.
      The uncommon feature of this case was the presence of a spleen abscess identified
      by computer tomography of the abdomen. Patient evolution was favorable after
      treatment with antibiotics, with complete regression of the lesions.

PMID- 9927827
TI  - [Disseminated cutaneous sporotrichosis as the initial manifestation of acquired
      immunodeficiency syndrome--case report].
AB  - The authors report a case of disseminated cutaneous infection with Sporothrix
      schenckii in a previously asymptomatic HIV-infected 30 year-old man. Extensive
      cutaneous involvement was observed with suppurative collections and ulcerations.
      The agent was isolated in culture. Treatment with liposomal amphotericin B proved
      to be effective.

PMID- 9927828
TI  - [Prevalence and epidemiological aspects of enteroparasites in the population of
      Sao Jose da Bela Vista, Sao Paulo].
AB  - The prevalence of intestinal parasites and its epidemiological aspects were
      studied in individuals of both sexes seen at the Outpatient Service of the
      Municipal Health Center and Sao Vicente Public Hospital in Sao Jose da Bela Vista
      (SP) from January 1992 to December 1996. The percentage of parasitic infestation
      was 44.4%, with the occurrence of protozoa and helminths. The high occurrence of
      parasitism was attributed to the low socioeconomic and educational level of the
      population and to the precarious hygiene conditions in their households.

PMID- 9927829
TI  - Plasmodium vivax resistance to chloroquine (R2) and mefloquine (R3) in Brazilian
      Amazon region.
AB  - We report for the first time a patient with malaria due to Plasmodium vivax who
      showed R2 resistance to chloroquine and R3 resistance to mefloquine in the
      Brazilian Amazon region based on WHO clinical criteria for diagnosis of malaria
      resistance. Failure was observed with unsupervised oral chloroquine, chloroquine
      under rigorous supervision and mefloquine in the same scheme. Finally, the
      patient was cured with oral artesunate.

PMID- 9927830
TI  - [Calcium channel antagonists and non-cardiac surgery in ischemic cardiopathy].

PMID- 9927831
TI  - [Diltiazem compared with placebo in the prevention of myocardial ischemia during
      non-cardiac surgery].
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of
      intravenous diltiazem to prevent myocardial ischemia during surgery on patients
      with ischemic heart disease undergoing non cardiac surgery under general
      anesthesia. PATIENTS AND METHOD: Sixty patients scheduled for elective non
      cardiac surgery under general anesthesia were randomly assigned to two groups to
      receive diltiazem or placebo under double blind conditions. After an intravenous
      dose of 0.15 mg/kg of diltiazem or an equivalent amount of placebo, an infusion
      of 3 micrograms/kg/min of diltiazem or placebo was begun and continued until
      three hours after surgery. Thirty minutes after starting the infusion, anesthesia
      was induced by 0.1 mg/kg diazepam, 3 micrograms/kg of fentanyl and 0.3 mg/kg of
      etomidate. Intubation followed administration of 0.6 mg/kg of atracurium.
      Anesthesia was maintained with N2O/O2 and halothane and was the same for both
      groups. DII and V5 leads were monitored on a Cardiowiss CM-8 ECG machine that
      allowed us to set the alarm when ST segment variations reached 1 mm above or
      below baseline. We analyzed the number, intensity and duration of ischemic
      episodes recorded, as well as hemodynamic variables and side effects. RESULTS:
      Data for 46 patients were valid. At least one ischemic episode was experienced by
      15% of patients in the placebo group and 1 in the diltiazem group (p < 0.05). The
      episodes were related to increased systolic arterial pressure (p = 0.04). ST
      segment decreases were 1.1 to 3.6 mm (1.75 +/- 0.7) (mean +/- SD) and lasted
      between 1 and 45 minutes (11.62 +/- 13.26) (mean +/- SD). No significant side
      effects were observed. CONCLUSIONS: Intravenous diltiazem administered to
      patients with ischemic heart disease under general anesthesia for non cardiac
      surgery was effective in our study for preventing intraoperative ischemic
      episodes.

PMID- 9927832
TI  - [Usefulness of radiologic monitoring of epidural catheters using epidurography].
AB  - INTRODUCTION: Peridural analgesia involves a segmental block which at the
      thoracic level allows for early pulmonary recovery after chest or high abdominal
      surgery. The approach is difficult in children for reasons related to anatomy,
      maintenance, insertion of the catheter and dosing. OBJECTIVE: To report the
      radiologic monitoring of epidural catheter placement by epidurography as a
      technique for placing the epidural catheter in 17 patients for whom postoperative
      analgesia was to be provided by the same route. PATIENTS AND METHODS: Eighteen
      children (aged from 2 to 12) were given general anesthesia followed by epidural
      anesthesia. After catheterization of the epidural space, 1 or 1-5 ml of contrast
      was injected. Immediately afterwards an X-ray of the thoracic or lumbar spinal
      column, as appropriate to each case, was obtained. Epidural analgesia was
      provided with a mixture of bupivacaine 0.125% and fentanyl, in continuous
      perfusion or in fractionated doses. RESULTS: Placement of the catheter tip was
      confirmed in 17 cases by visualization of symmetry and the presence of contrast
      medium in the epidural space. In one case we observed extravasation of contrast
      medium, which had invaded the paravertebral space. The course was linear in 17
      cases, with no looping. No complications related to injection of contrast medium
      were observed. CONCLUSIONS: Epidurography provides objective monitoring of tip
      placement and trajectory of epidural catheters, advantages which argue in favor
      of more frequent application of this imaging technique.

PMID- 9927833
TI  - [Our experience with the Univent tube].
AB  - INTRODUCTION: We describe our experience in managing single lung ventilation
      (SLP) with the Univent bronchial blocker tube from 1993 to the present. PATIENTS
      AND METHOD: Patients were grouped based on the following criteria: use of a
      double lumen tube as an alternative to SLP (group 1), use of SLP and tracheotomy
      (group 2), or difficult or dangerous orotracheal intubation (group 3). RESULTS:
      The mean age of the 32 patients (22 men and 10 women) studied was 45.7 +/- 12.2
      years. Mean weight was 67.9 +/- 13.4 kg. Ten patients were physical status ASA I,
      10 were ASA II, 10 were ASA III and 2 were ASA IV. Group 1 contained 28 patients
      (18 receiving right SLP and 10 receiving left SLP; use of SLP failed to collapse
      the lung in 4 patients [14.3%]). Group 2 consisted of 5 patients and group 3
      contained 11. The Univent tube was used in 4 patients in group 3 who did not
      require use of SLP but whose intubation was considered difficult and in whom
      laryngoscopic findings were consistent with a Cormack-Lehane group III
      classification. The Univent bronchial blocker tube was used as a guide, such that
      intubation was achieved on the first try. The tube was removed from 3 patients
      (8%) in the intensive care recovery ward. The remaining 29 tracheas were
      extubated in the operating room. No side effects attributable to the Univent tube
      were recorded. CONCLUSIONS: The advantages and disadvantages of this new tool for
      the management of SLP mean that it may be useful for specific situations (such as
      for SLP with difficult intubation or in patients with tracheotomies or aneurysms
      of the descending thoracic aorta), but that it does not replace conventional
      methods. We believe that the Univent bronchial blocker tube should be available
      as part of operating room equipment.

PMID- 9927834
TI  - [Drug allergy in a population of surgical patients].
AB  - OBJECTIVES: To determine the prevalence of drug allergies in a population of
      surgical patients. To establish a clinical classification of events as being very
      or not very likely to be allergic reactions. To detect which drug groups are
      associated with greater incidence of anaphylactic reaction and to analyze the
      severity of such reactions. PATIENTS AND METHODS: Epidemiological study. During a
      preoperative interview, patients were asked if they were aware of the existence
      of any episode of allergy to drugs. If a patient answered yes, a specific data
      collection questionnaire on allergies was completed. Based on signs and symptoms
      described by the patient, reactions were classified as indicating high likelihood
      of allergy, low likelihood of allergy, or as being of unknown origin. RESULTS: We
      questioned 1,218 patients (754 women/464 men), of whom 159 (13.05%) reported
      being allergic to drugs. The total number of drugs employed was 212 (1.34
      drugs/patient). Antibiotics (54.7%), nonsteroidal anti-inflammatory drugs
      (NSAIDs) (19.3%), radiological contrast media (6.1%) and local anesthetics (4.7%)
      were the substance groups most often mentioned. We classified 74.5% of the
      reactions as indicating high likelihood of allergy, 19.8% as indicating low
      likelihood, and 5.6% to be of unknown origin. The skin was involved in 72.1% of
      the reactions that were highly likely to have been caused by allergy; 6.9% of
      these reactions involved the respiratory tract, 4.4% the circulatory system, 12%
      the skin plus respiratory tract, and 4.4% the skin plus respiratory and
      circulatory systems. The most severe reactions (16.4%) were associated with
      radiological contrast media (36.4%), NSAIDs (33.3%) and intravenous
      administration (38.1%). Signs of latex allergy were seen in 0.4% and signs of
      allergy to hair dyes in 0.9%. All allergy tests were negative in all these
      patients. CONCLUSIONS: Drug allergy is reported by 13% of patients. It is highly
      likely that 74.5% of reactions are due to allergy. Antibiotics are the most
      frequently implicated drugs, followed by NSAIDs. The most serious reactions are
      caused by radiological contrast media and NSAIDs. Intravenous administration
      causes the most serious reactions.

PMID- 9927835
TI  - [Epidural anesthesia and analgesia in the perioperative treatment of a patient
      with Kartagener syndrome].
AB  - Kartagener's syndrome is an inherited disease characterized by a triad of
      symptoms--bronchiectasis, situs inversus and sinusitis--and is classified as an
      immotile cilia syndrome. Patients may experience specific airway problems when
      undergoing anesthesia for surgical procedures. We report the case of a woman with
      Kartagener's syndrome who underwent surgery under epidural anesthesia with
      postoperative epidural analgesia, both techniques proving successful.

PMID- 9927836
TI  - [Common variable immunodeficiency associated with autoimmune thrombocytopenia:
      anesthetic management].
AB  - A 44-year-old man diagnosed of common variable immunodeficiency associated with
      thrombopenia due to autoimmunity required anesthesia for anal fissure repair and
      hemorrhoidectomy. Hemostatic complications developed after surgery, with extreme
      thrombopenia (1,000 platelets/pl) and analytical changes that necessitated
      administration of six units of platelets from apheresis, as well as
      immunoglobulins, antifibrinolytic agents (e-aminocaproic acid) and granulocytic
      colony stimulating factors. Anesthesia for such patients is reviewed, with
      emphasis on careful management of the airways, preparation of sufficient material
      for surgery (rapid transfusion equipment, large caliber intravenous catheters,
      sterile material) and orientation of anesthetic technique toward general
      anesthesia through a laryngeal mask.

PMID- 9927837
TI  - [Extracorporeal membrane oxygenation in myocardial failure after pediatric heart
      surgery].
AB  - In spite of progressive improvement not only in myocardial protection but also in
      anesthetic and surgical techniques, the repair of complex congenital heart
      defects can still lead to cardiopulmonary compromise refractory to conventional
      treatment. We describe two patients in whom successful surgical repair of
      congenital heart defects was followed by severe heart failure refractory to
      medical treatment. Both patients were managed by extracorporeal membrane
      oxygenation (ECMO). We discuss the indications, contraindications and use of ECMO
      in the postoperative intensive care unit.

PMID- 9927838
TI  - [General anesthesia using a laryngeal mask and anesthesia by epidural catheter in
      a case of Charcto-Marie-Tooth type I disease].

PMID- 9927839
TI  - [Anesthesiology without recovery room care].

PMID- 9927840
TI  - [Use of cisatracurium in a case of myasthenia gravis].

PMID- 9927841
TI  - [Anesthesia in a patient with Rosai-Dorfman disease].

PMID- 9927842
TI  - [Registry of activities of the Section of Hemodynamics and Interventional
      Cardiology in 1997].
AB  - The results of the Spanish Registry of Hemodynamic and Interventional Cardiology
      in 1997 are presented. The Registry collects the activity of 83 centers which
      constitute all the cardiac catheterization laboratories in Spain. The main
      activity was adult cardiac catheterization in 75 centers and exclusively
      pediatric cardiac catheterization in 8. A total of 72,370 diagnostic
      catheterization procedures, 80% coronary angiographies (57,960; 1,462 per million
      inhabitants), were performed which represents a 13% total increase compared to
      1996. Coronary intervention increased by 23% compared to 1996, for a total number
      of 18,545 procedures. The ratio of coronary interventions per million inhabitants
      was 468. Success rates of coronary interventions (91.3%) and complications (3.7%)
      were similar to those registered in previous years. In the specific field of
      revascularization devices, there has been a dramatic increase in the use of
      stents. In 1997, coronary stents were employed in 11,417 cases (a 61% increase
      compared to 1996) which represents 61.5% of all coronary revascularizations
      procedures. A total of 14,170 prosthesis were implanted, 72% in a elective way,
      with a low rate of complications (0.95% subacute closure; 1.45% myocardial
      infarction and 0.75% mortality). Compared to 1996, directional coronary
      atherectomy (92 procedures) showed a slight decrease, whereas rotational
      atherectomy (554 procedures) increased by 49% with double the number of centers
      performing this technique. As in previous years, a slight decrease (7% compared
      to 1996) in adult valvuloplasties (559 vs 599) was noted. Pediatric
      interventional procedures decreased by 17% (465 vs 558 procedures) compared to
      the 1996 Registry.

PMID- 9927843
TI  - [Primary angioplasty is elective reperfusion therapy in the treatment of acute
      myocardial infarction. Arguments in favor].
AB  - Thrombolytic treatment has demonstrated its efficacy on acute myocardial
      infarction. However, it cannot be used in a significant number of patients and it
      doesn't achieve adequate reperfusion in a great percentage of cases. Primary
      angioplasty, a treatment which can be used in the majority of acute myocardial
      infarction patients, obtains artery patency in more than 90% of cases, with a
      better perfusion in the infarct territory and fewer reocclusion rates compared to
      thrombolysis. Consequently, primary angioplasty is associated with a lower
      mortality rate, and a lower incidence of recurrent ischemia and hemorrhagic
      stroke during hospitalization. Coronary artery stents and new antiplatelet agents
      have improved the short-term and mid-term results of primary angioplasty.
      Currently, when the facilities and trained personal are available, primary
      angioplasty should be the treatment of choice in acute myocardial infarction.

PMID- 9927844
TI  - [Primary angioplasty is elective reperfusion therapy in the treatment of acute
      myocardial infarction. Arguments against].
AB  - The primary goal of treatment for patients with evolving infarction should be the
      rapid and sustained restoration of antegrade coronary blood flow. Thrombolytic
      therapy is an effective and widely available therapy to achieve this aim.
      However, thrombolysis does not achieve recanalization of the infarct-related
      artery in 20% of patients and early complete reperfusion (TIMI 3 flow) is
      achieved in only 50%. Some small randomized trials suggested that primary
      angioplasty was more effective than thrombolytic therapy in restoring patency and
      preventing reocclusion of the infarct-related artery. Furthermore, the patients
      treated with immediate angioplasty had a lower incidence of recurrent ischemia,
      reinfarction and death than those given thrombolysis. More recently, the GUSTO
      IIb primary angioplasty substudy, found that primary angioplasty provided only a
      small short-term clinical benefit over thrombolytic therapy with t-PA, in the
      combined end-point of death, reinfarction and nonfatal disabling stroke at 30
      days. At six months, this small benefit had vanished. The major limitation for
      primary angioplasty is the restricted availability of the procedure. Only when
      angioplasty can be performed promptly, in centers with extensive experience in
      angioplasty and with adequate catheterization facilities and support personnel,
      may it be used as the reperfusion strategy of choice. Nowadays, for the vast
      majority of patients, thrombolysis remains the best available treatment for acute
      myocardial infarction.

PMID- 9927845
TI  - [Patients with acute coronary syndrome: therapeutic approach (management
      patterns) and 1-year prognosis in a tertiary general hospital].
AB  - BACKGROUND: To assess the determinants of short-term and one-year prognosis of
      all patients with suspected acute coronary syndrome seen by the cardiologist on
      duty in the Emergency Service of a tertiary hospital during a six month period.
      PATIENTS AND METHODS: 153 consecutive patients with a diagnosis of acute
      myocardial infarction, 225 with a diagnosis of unstable angina and 89 with a
      diagnosis of atypical chest pain were identified and their in-hospital
      characteristics and one-year prognosis were prospectively assessed. RESULTS: Age
      was higher than 65 years in 53% of acute myocardial infarction and in 54% of
      unstable angina patients. Only 3 patients were lost to follow-up. 35% of acute
      myocardial infarction patients had died or had reinfarction after one year and
      16% of unstable angina patients had died or had suffered acute myocardial
      infarction. Baseline features, management patterns and prognosis of patients
      admitted with acute myocardial infarction to the Cardiology Service, to other
      hospital areas or to other hospitals were markedly different, and admission in
      areas other than the Cardiology Service was an independent mortality predictor.
      In unstable angina, complications happened in patients older than 75 years, those
      with previous revascularization procedures, those undergoing revascularization or
      those with lesions not deemed revascularizeable. CONCLUSIONS: a) In the study
      population there was a predominance of elderly patients; the proportion of
      patients with poor prognosis was considerably high; b) a sizeable proportion of
      patients with severe complications was scarcely represented in the major clinical
      trials; c) the possibility arises of a distribution of care resources tending to
      concentrate the greater therapeutic efforts in the patients with good prognosis.

PMID- 9927846
TI  - [Ambulatory blood pressure monitoring in the aged. The EPICARDIAN study. The
      EPICARDIAN Work Group].
AB  - OBJECTIVE: To determine reference values for ambulatory blood pressure in a
      random sample of Spanish elderly population, and their correlations with office
      blood pressure measurements. METHODS: A representative random sample was
      obtained, stratified by sex and age, of 1,227 elderly subjects aged > 65 years,
      residents in an urban district, Barrio de Salamanca, or Madrid, Spain. In a
      random subsample (n = 420), two different blood pressure measurement approaches
      were performed: Office blood pressure and twenty-four hour ambulatory blood
      pressure (spacelabs 90207) were recorded, and two periods were defined: awake and
      sleeping, on the basis of the daily activities. Hypertension was defined if the
      average of casual blood pressure was > or = 140/90 mmHg or if there was current
      use of antihypertensive drugs. RESULTS: Among the 420 participants, 333
      ambulatory blood pressure monitorings were performed, 301 with valid registers,
      of whom 105 were receiving antihypertensive drug treatment. Office, 24 hour,
      awake and sleeping pressures averaged 147/84 mmHg, 128/72 mmHg, 132/77 mmHg and
      122/66 mmHg respectively. Differences between whole sample and no treated group
      were not significant (p = 0.2), nor between the whole sample and the treated
      group (p = 0.7). Office blood pressure was markedly higher than 24 hour and awake
      averages (20 and 15 mmHg for systolic and 12 and 7 mmHg for diastolic,
      respectively). The differences between clinic and awake average blood pressures
      were significantly higher in females (p = 0.001) and increased, in both genders,
      as age (p = 0.001) and clinic blood pressure values (p < 0.000) increased.
      Correlation coefficients between office and the average awake period of the
      ambulatory blood pressures were of 0.60 and 0.48 for systolic and diastolic
      respectively. The ambulatory blood pressure value equivalent to 140/90 mmHg when
      obtained by causal measurement, was 15 mmHg lower when considering the 24 h
      average, or 10 mmHg lower when the awake averages. CONCLUSION: Ambulatory
      systolic and diastolic blood pressure values in the elderly are markedly lower
      than office values, specially in the case of systolic blood pressure. Differences
      in results between the two methods increase with age and with clinic blood
      pressure values, and are bigger in females. The cut-off point for ambulatory
      blood pressure monitoring equivalent to 140/90 mmHg in the casual measurement is
      of 125/75 mmHg for the 24 hour average and of 130/80 mmHg for awake average.

PMID- 9927847
TI  - [Trends of morbidity and mortality in chronic heart failure in Catalonia].
AB  - INTRODUCTION: The epidemiology of chronic heart failure, specifically its
      morbidity and mortality, is insufficiently known, despite the fact that it has an
      important economic impact because of the pharmacological treatment and the high
      hospitalization rate. OBJECTIVE: To analyze the trends of mortality and morbidity
      of chronic heart failure in Catalonia during the periods 1975-1994 and 1989-1994
      respectively. PATIENTS AND METHODS: Specific mortality and morbidity rates (ages
      45-65, and older than 65) were calculated for both sexes. Standardised mortality
      rates were also calculated for mortality rates using the European population as
      the reference. RESULTS: The trend of mortality of chronic heart failure in the
      population of 45-65 is stable, the rates being higher for men than for women. The
      trend in the age group older than 65 shows an important increase from 1983 on,
      higher in women than in men. Morbidity (hospitalization discharge rates)
      increases slightly in the population of 45-65 years, especially in men; in the
      population older than 65 an important increase is observed for both sexes.
      CONCLUSIONS: Trend of mortality is increasing specifically in women older than
      65, while trends of morbidity are clearly increasing for both age groups.

PMID- 9927848
TI  - [Primordial prevention and control of the population burden of heart failure].

PMID- 9927849
TI  - [Anthropometric and dietary determinants of blood levels of HDL cholesterol in a
      population-based study. The REGICOR study. Researchers of the REGICOR study].
AB  - OBJECTIVES: The aim of the present study was to identify dietary and
      anthropometric factors influencing HDL cholesterol levels in the region of
      Girona. POBLATION AND METHODS: A cross-sectional study was designed with random
      recruitment and 798 men and 862 women were included. Anthropometric variables
      were collected, the energy expenditure in physical activity was calculated and a
      dietary questionnaire was supplied in order to obtain nutritional data.
      Furthermore, lipid levels and lipoprotein concentrations were determined.
      RESULTS: Significant differences were found in serum triglycerides, body mass
      index, glucose levels and alcohol intake between the upper and the lower tertils
      of HDL cholesterol in both men and women. In men, energy expenditure in physical
      activity was significantly associated with HDL cholesterol levels, as well as
      total fat and monounsaturated fat. In women, together with the waist-to-hip ratio
      and fasted glycemia, vitamin C was the dietary factor positively associated with
      HDL cholesterol levels. CONCLUSIONS: Moderate alcohol intake, physical activity,
      vitamin C consumption and optimizing body weight strongly contribute to increased
      HDL cholesterol levels in our region.

PMID- 9927850
TI  - [HDL cholesterol and cardiovascular mortality in Spain].

PMID- 9927851
TI  - [Sudden death in hypertrophic myocardiopathy].
AB  - Hypertrophic cardiomyopathy is the most common cause of sudden death in young
      individuals who are otherwise healthy. Risk of sudden death is highest in
      patients who are between 14 and 35 years old. Several mechanisms are involved in
      sudden death: ventricular arrhythmias, supraventricular arrhythmias leading to
      cardiac collapse, bradycardias and severe ischemia. Many studies have analyzed
      how to identify high risk patients. The factors that best identify high risk
      patients are: previous history of sudden death or syncope, induction in adults of
      sustained ventricular arrhythmias, the presence of non-sustained ventricular
      tachycardia in symptomatic patients, the presence of ischemia associated with
      hypotension in children, the presence of mutations in the beta-myosin heavy chain
      together with a family history of sudden death and a poor left ventricular
      ejection fraction. Risk stratification should be done on an individualized basis.
      In those patients in whom a high risk for sudden arrhythmic death is suspected,
      the only current effective treatment is the implantable defibrillator.

PMID- 9927852
TI  - [Anomalous origin of the left coronary artery from the pulmonary artery in
      adults. Long-term follow up].
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is a
      serious pathology, that untreated supposes a high mortality. Usually it becomes
      symptomatic in early infancy, but some cases reach adult life with no symptoms.
      We report four cases diagnosed in teenagers and adults, three of them with the
      oldest ages known in worldwide literature and one of them the oldest reported
      until now. We have completed a long follow-up in the various surgical techniques,
      where we did not observe any differences in their prognosis, and we recommend an
      anti-arrhythmia treatment joined with surgical treatment in adult patients with
      this pathology.

PMID- 9927853
TI  - [Abscess of the mitral-aortic confluence and perforation of the mitral valve in a
      patient with Brucella endocarditis].
AB  - We report a case of Brucella aortic valve endocarditis in a 36 year-old patient
      with no underlying heart disease who required urgent surgery. In the
      postoperative follow-up, he suffered from congestive heart failure due to an
      anterior mitral valve rupture. In the echocardiogram, a periprosthetic abscess
      was seen and a second intervention was necessary. This report suggests that
      treating Brucella endocarditis requires a combined medical and surgical approach.

PMID- 9927855
TI  - [Arterial switch: aortocoronary bypass with interposition of
      polytetrafluoroethylene (Gore-tex) vascular graft].
AB  - We report a case of an infant with transposition of the great arteries
      accompanied by an unusual coronary artery pattern, in whom an expanded
      polytetrafluorethylene (Gore-tex) graft to the right coronary artery was used
      during surgical correction (switch arterial), with a postsurgical follow-up time
      of 8 months.

PMID- 9927854
TI  - [Austrian's syndrome (endocarditis, meningitis and pneumonia caused by
      Streptococcus pneumoniae). Apropos of a rare case].
AB  - We report a case of a mitral endocarditis caused by Streptococcus pneumoniae in a
      48 year old man diagnosed with moderate mitral stenosis and liver cirrhosis. The
      clinical features were fever with penicillin-sensitive pneumococcal bacteremia,
      meningitis and pneumonia. Only transesophageal echocardiography could confirm the
      presence of vegetations. In spite of vancomycin therapy, the patient required
      mitral valve replacement, with good results. Some clinical aspects of this
      uncommon cause of infective endocarditis are discussed.

PMID- 9927856
TI  - Normal relationships between cardiovascular variables in active orthostatism and
      clinostatism in postural change.
AB  - OBJECTIVE: Autonomic modulation of hemodynamics, essential for the preservation
      of homeostasis, is well tested by the abrupt postural change from clinostatism to
      active orthostatism. The aim of this work was to study normal relationships
      between the cardiovascular variables in active orthostatism and those in
      clinostatism. METHODS: Hemodynamic parameters in clinostatism and orthostatism
      were easily measured in 20 healthy subjects of both sexes, aged between 33 and 78
      years, without treatment, using the non-invasive thoracic electric bioimpedance
      method. RESULTS: Cardiovascular variables values in orthostatism are linearly
      related with their values in clinostatism. CONCLUSIONS: Results show that
      cardiovascular variables in active orthostatism are linearly related with their
      values in clinostatism, each variable being specially regulated. A clinostatism
      and orthostatism intraindividual correlation was obtained, which provides an
      easily accessible method of detection and interpretation of autonomic
      dysfunctions, without deleterious consequences for the subjects, which can be
      very useful for research on physiopathologic mechanisms.

PMID- 9927857
TI  - [Recovery of respiratory parameters and oxygen consumption during the recovery
      phase of cardiopulmonary exercise test in patients with dilated cardiomyopathy].
AB  - OBJECTIVE: To analyse the recovery of oxygen consumption (VO2), ventilation (VE)
      and carbon dioxide production (VCO2) after maximal cardiopulmonary exercise
      testing, and to assess the possibility of recovery parameters becoming new
      markers of functional impairment. METHODS: Thirty-eight patients (30 males, mean
      age 56 +/- 11 years) with dilated cardiomyopathy performed maximal, symptom
      limited, treadmill exercise test with breath-by-breath respiratory gas analysis.
      The patients were divided in two groups, according to maximal oxygen consumption
      above or below 14 ml/kg/min (group I and group II, respectively). During the
      recovery, we analyzed the time to reach 50% of the maximal values of VO2 (T1/2 r
      VO2), VE (T1/2 e VE) and VCO2 (T1/2 r VCO2) in each group. RESULTS: Twenty-seven
      patients had a VO2max above 14 ml/kg/min (group I) and 11 had a VO2max below 14
      ml/kg/min (group II). The results were as follows: T1/2 r VO2max 109 +/- 21 sec
      in group I versus 177 +/- 79 sec in group II (p = 0.0001). T1/2 r VCO2max 124 +/-
      28 sec in group I versus 201 +/- 88 sec in group II (p = 0.0001) and T1/2 rVEmax
      146 +/- 47 sec in group I versus 229 +/- 47 sec in group II (p = 0.0002).
      CONCLUSIONS: Patients with a poor functional capacity show a delay in the half
      recovery times of oxygen consumption, ventilation and carbon dioxide production.
      These data suggest that these parameters may be used as new markers of the level
      of functional impairment.

PMID- 9927858
TI  - [Can the ventilatory equivalent for carbon dioxide predict the severity of
      functional impairment in patients with cardiac insufficiency?].
AB  - OBJECTIVE: To evaluate whether the changes in the ventilatory equivalent for
      carbon dioxide (VE/VCO2), during the early stages of cardiopulmonary exercise
      testing, can predict maximal oxygen consumption (VO2max) in patients with chronic
      heart failure. METHODS: We studied 38 patients (30 males, mean age 56 +/- 11
      years) with chronic heart failure. All patients performed maximal symptom
      limited, treadmill exercise test with breath-by-breath respiratory gas analysis.
      They were divided in two groups according to their maximal oxygen consumption
      (group I-VO2max above 14 ml/kg/min and group II-VO2max below 14 ml/kg/min). In
      both groups, we analysed VE/VCO2 at rest, at the anaerobic threshold (AT) and at
      peak exercise, and the percentage of VE/VCO2 reduction from rest to AT. RESULTS:
      Eleven patients had a VO2max below 14 ml/kg/min (group II). At rest VE/VCO2 = 53
      +/- 13 in group II versus 47 +/- 10 in group I (p = 0.048), at the AT VE/VCO2 =
      46 +/- 12 in group II versus 36 +/- 7 in group I (p = 0.001) and at peak exercise
      VE/VCO2 = 46.2 +/- 13 in group II versus 36.2 +/- 6 in group I (p = 0.0002).
      There was a 24% reduction in the VE/VCO2, from rest to AT in group I, compared to
      a 16% reduction in group II (p = 0.004). A reduction in the VE/VCO2 from rest to
      AT less than 16% predicted a VO2max below 14 ml/kg/min with a sensitivity of 60%
      and a specificity of 93%. CONCLUSIONS: Patients with severe functional impairment
      have higher values of VE/VCO2 in all exercise stages. A reduction of VE/VCO2 from
      rest to anaerobic threshold of less than 16% is a high specific predictor of a
      VO2max below 14 ml/kg/min.

PMID- 9927859
TI  - [Is the stress test useful in the detection of post-angioplasty restenosis?].
AB  - Restetenosis is still the greatest limitation of coronary angioplasty (PTCA). The
      systematic use of ergometry (PE) with the objective of identifying restenosis is
      controversial and, namely, the ACC/AHA does not recommend its routine use. Our
      objective was to conduct a retrospective study of the use of PE when performed
      late (3 to 6 months) for the detection of restenosis. As a protocol, our group
      performed "late" PE on all the patients without contraindications, the patients
      with positive ergometry or CCS class II-IV angor submitted to angiographic
      control. Between January 1996 and July 1997, 121 patients (pts) were submitted to
      PTCA. Our study population was composed of patients submitted to complete
      revascularisation with follow-up in our centre: 59 pts (49%) with an average age
      of 58 +/- 12 years, 82% male. Eighty-three percent of the pts had
      revascularisation in a context of unstable angina, 10% in the acute phase of
      myocardial infarction and 7% due to chronic angina. Stents were implanted in 42%
      of the pts. In the follow-up after six months, 7 pts complained of CCS class II
      or III angor. The ergometry showed positive electrocardiographic criteria in 11
      pts (18.6%). All pts with angor had positive PE. All these pts were submitted to
      angiographic control; restenosis (residual stenosis equal to or above 50%) was
      observed in all the patients who complained of angor (100% positive predictive
      value); restenosis occurred in 9 pts with positive ergometry (82% positive
      predictive value). In asymptomatic pts, PE indicated 2 pts with restenosis (2/59
      3.4%) and two false positive (2/11-18%). At six months, PE detected 22% of the
      pts with restenosis. In conclusion, complete post-revascularisation angor due to
      coronary angioplasty has a higher positive predictive value than ergometry.
      However, the stress test, performed systematically, can identify an additional
      percentage of pts with restenosis with an acceptable percentage of false
      positives.

PMID- 9927860
TI  - [Abciximab (ReoPro) in primary angioplasty].
AB  - The aim of the study was to evaluate the efficacy and safety of abciximab
      (ReoPro) in primary percutaneous transluminal coronary angioplasty (P.T.C.A.) in
      patients with myocardial infarction (M.I.). From June 96 to October 97, 16
      patients with a mean age of 58 +/- 12 years, 86% males, with myocardial
      infarction (less than 12 hours of pain) were treated with ReoPro during P.T.C.A.
      The infarction was anterior in seven patients (44%), inferior in eight patients
      (50%) and non-Q wave in one patient (6%). Nine patients (47%) had a previous
      history of angina or myocardial infarction. The mean time from onset of symptoms
      to hospital arrival was 306 +/- 370 min and the mean time between hospital
      admission and the beginning of the procedure was 79 +/- 86 min. P.T.C.A. was
      performed on the anterior descending artery and right coronary in 44% and 56%,
      respectively. The success rate was 94%. Stents were used in 31%. In patients with
      angiographic success, we obtained TIMI III flow in 14 patients and TIMI II in one
      patient. No complications arose during P.C.T.A; no significant changes in
      platelets or hemoglobin were observed after the procedure. In this group of
      patients, one case of hematoma was found at the site of puncture with no need for
      transfusion. During hospitalization, no major coronary events were found. During
      the follow-up of 10.5 +/- 4.9 months, one patient died after non cardiac surgery
      and one patient was submitted to coronary artery bypass graft; there was no
      reinfarction nor new P.T.C.A. CONCLUSIONS: In our experience with ReoPro during
      direct angioplasty, we obtained good immediate and long term results, with no
      significant bleeding complications.

PMID- 9927861
TI  - [Cadmium and cardiac muscle cell - biomarkers of oxidative stress - experimental
      work].
AB  - OBJECTIVE: To study in several tissues (heart, kidney and liver) of Halobatrachus
      didactylus the cellular response induced by an acute exposure to a sublethal
      cadmium concentration. DESIGN: Fifteen species of H. didactylus (marine teleost)
      were divided in to three groups: CTRL: control group, the fish were injected with
      a saline solution; 24 H: 1 mg/kg of cadmium chloride was injected and the fish
      were sacrificed after 24 hours; 7 D: the fish were subjected to the same cadmium
      concentration and sacrificed 7 days after injection. INTERVENTIONS: Superoxide
      dismutase--SOD (McCord & Fridovich, 1969) and catalase--CAT (Clairborne, 1985)
      activities were determined in the cytosolic and mitochondrial fractions of these
      three tissues. The lipid degradation products were also determined by the
      tiobarbithuric acid (TBA) test. MEASUREMENTS AND RESULTS: Cadmium induced an
      increase in SOD activity in both fractions (cytosolic and mitochondrial) of these
      H. didactylus tissues. The highest levels of activity observed were located at
      mitochondrial fraction and in the heart. There was a significant increase in CAT
      activity in both liver and heart tissue fractions after cadmium exposure. The
      highest values were observed in the liver. The kidney presented a different
      response: there was a rise in CAT activity only in the mitochondrial fraction
      after seven days of exposure. There were no significant changes in lipid
      degradation products in any of these tissues after cadmium exposure. CONCLUSIONS:
      The two antioxidant enzymes studied in the heart, kidney and liver of H.
      didactylus demonstrated a high sensitivity to oxidative stress induced by cadmium
      and presented a high potential as cellular biological makers. The results
      indicate membrane lesion caused by lipid peroxidation did not occur, which
      suggests an efficient response of the cellular protection mechanisms against
      cadmium cytotoxicity.

PMID- 9927862
TI  - [Total occlusion of the left common coronary artery--a case report].
AB  - Total chronic occlusion of the left main coronary artery is an unusual finding.
      After a review of the literature, the authors present a case report of a patient
      with stable angina and total occlusion of the left main coronary artery, right
      coronary with atherosclerotic lesions and normal ventricular function.

PMID- 9927864
TI  - [Image of the month. What collapse!].

PMID- 9927865
TI  - [Drug clinics. How I treat a patient with a low concentration of HDL
      cholesterol].
AB  - The decision to treat an individual with low HDL cholesterol level depends on his
      overall cardiovascular risk profile and the therapeutic strategy is based upon
      the characteristics of the lipid profile (isolated abnormality, associated
      hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment
      must favour diet and exercise, before considering a possible pharmacological
      approach. Results are usually acceptable with better life habits and appropriate
      diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From
      a pharmacological point of view, the best results are obtained with fibrates or
      nicotinic acid. However, results are often disappointing when low HDL cholesterol
      level is isolated.

PMID- 9927866
TI  - [Clinical case of the month. Apropos of pancytopenia in a seropositive patient].
AB  - A 37-year old patient, HIV-1-infected, consulted for progressive weakness and
      dyspnea on exertion, increasing over three months. Complete blood count showed
      pancytopenia, while the bone marrow revealed severe hypoplasia. Other
      investigations, including serology for CMV, vitamin levels, Coombs test,
      gastroscopy and colonoscopy were non contributing. A diagnosis of zidovudine
      induced medullary aplasia was made; the clinical course was favourable after this
      drug was replaced by triple therapy. The authors discuss the differential
      diagnosis of cytopenias in the patient infected by HIV and they suggest a
      diagnostic approach.

PMID- 9927867
TI  - [Liver transplantation: experiences and results of a program at the University of
      Liege].
AB  - The orthotopic liver transplantation (OLT) program of the University of Liege was
      initiated in 1986. Between 1986 and December 1998, 150 adult OLT have been
      performed in our institution, including 18 liver retransplantations, 1 combined
      heart and liver transplantation and 3 combined liver and kidney transplantations.
      The aim of this study was to report the last 3 years of our experience. From
      January 1996 to November 1998, we performed 50 OLT on 49 patients. Three were
      retransplantations and two were combined liver and kidney transplantations.
      Fourty-three patients were transplanted for chronic liver disease and 6 for acute
      or subacute hepatopathy. Mean waiting time on the list was 4 weeks.
      Immunosuppression was based on triple therapy (cyclosporin A/tacrolimus,
      steroids, azathioprine), with steroid and azathioprine withdrawal in most of the
      patients after 3 months. In the chronic liver disease group, operative (< 30
      days) survival was 95% (peroperative myocardial infarction in 2 patients). In the
      acute liver disease group, postoperative survival was 66%. No perioperative death
      occurred in 1997 and 1998. Actuarial one year survival was 87%. In our
      experience, OLT has become a safe procedure.

PMID- 9927868
TI  - [Genetic aspects of the 46, XX male].
AB  - The XX males represent a proportion of 1/25 of all patients suffering of the
      Klinefelter syndrome. From a clinical and endocrinological point of view, they
      exhibit a hypogonadotropic hypogonadism. Isolated cases are rare and familial
      forms are exceptional. The XX males may be divided in 3 subgroups: 46, XX males
      with the SRY gene; 46, XX males without the SRY gene and XX/XY mosaics.

PMID- 9927869
TI  - [Breast implants].

PMID- 9927870
TI  - [Breast implants. Conventional breast examination].

PMID- 9927871
TI  - [Breast implants. Phosphor screens].

PMID- 9927872
TI  - [Breast implants. Evaluation of breast implants using magnetic resonance imaging
      (MRI)].

PMID- 9927873
TI  - [Breast implants. Conclusion: management].

PMID- 9927874
TI  - [Surgical hysteroscopy or hysterectomy in the treatment of benign uterine
      lesions. What to choose in 1998?].
AB  - In the past, the treatment of benign uterine lesions required, in many instances,
      a hysterectomy. These days, most cases can be successfully treated by
      hysteroscopy. To be reliable, this technique must lead to a significant reduction
      in the number of hysterectomies performed for benign uterine lesions. The
      electroresection technique is preferred to that using the Nd-YAG laser because of
      its lower cost and its equivalent efficacy. By using the uterine perfusion pump
      device, the risk of resorption syndrome can be reduced to its minimum. Submucosal
      myomas < 1 cm, benign endometrial hyperplasia and adenomyosis are the commonest
      benign lesions treated. Dysfunctional uterine bleeding can also be treated by an
      endometrectomy. A preoperative workup includes a transvaginal ultrasound and a
      biopsy. This ensures that only benign lesions that are accessible to a
      hysteroscopy will be submitted to this technique and that no cases of endometrial
      cancer or atypical hyperplasia would be ignored. This study presents 270 cases of
      operative hysteroscopy with a follow-up to 4 years. 82.8% of myomatous lesions
      were treated with success. The results for patients with benign endometrial
      polyps or benign endometrial hyperplasia are also excellent with only 4.6% and
      5.6% rate of secondary surgery respectively. Adenomyosis does not appear to be a
      good indication for hysteroscopy as only 37% of patients did not need a
      definitive hysterectomy. Rates of operative complications (post-operative
      bleeding, uterine perforation, resorption syndrome and difficulty of access) are
      acceptable and get less frequent as the surgeon experience increases.

PMID- 9927875
TI  - [Follow-up of patients treated by amiodarone].
AB  - Amiodarone is a highly effective antiarrhythmic agent. Its iodine content and
      tissue accumulation are however responsible for various side effects. In this
      article, we review the various amiodarone related side effects and propose a
      monitoring chart for patients treated by this specific agent.

PMID- 9927876
TI  - [Drug-induced cataracts].
AB  - The fact that corticosteroids, phenothiazines and myotics induce cataract is well
      known. Moreover some informations about lens opacities have been reported less
      frequently after the use of cytostatics, deferoxamine, phenytoine, isotretinoine,
      oral contraceptives, allopurinol, synthetics antimalarial agents, diazepam,
      tetracyclines and sulfamides. Occasionally some others drugs have been suspected
      from experimental observations to produce cataract. Amongst all these drugs,
      corticosteroids are the most often incriminated.

PMID- 9927877
TI  - [Respiratory function and surgical reduction of lung volume].
AB  - Emphysema is characterised by an enlargement of the terminal air spaces.
      Destructions of alveolar walls lead to a loss of the lung elastic recoil. The
      driving pressure for expiration is decreased and the outward forces acting on the
      bronchioles are lost, leading to bronchiolar collapse and airflow limitation.
      Hyperinflation of the lungs and overdistension of the chest wall cause the
      respiratory muscles to operate in unfavourable conditions. Patients with advanced
      emphysema have decreased quality of live: they are dyspneic at rest and are
      unable to perform exercise. Surgical excision of parts of diffusely emphysematous
      lungs (Lung Volume Reduction Surgery, LVRS) has been proposed since many years.
      Expansion of the remaining lung should increase lung elastic recoil and restore
      the outward forces on the bronchioles. It has been demonstrated that LVRS reduces
      dyspnea symptoms, improves exercise tolerance and enhances the quality of live.
      LVRS increases lung elastic recoil, airway conductance and maximal expiratory
      flow, reduces dynamic hyperinflation and improves the efficiency of the
      respiratory muscles. These improvements are maintained for at least 12 to 18
      months. Preoperative evaluation, surgical-induced modifications of pulmonary
      functions and postoperative exercise training are exposed.

PMID- 9927878
TI  - [Necrolytic migratory erythema].
AB  - Necrolytic migratory erythema (NME) is generally associated with glucagonoma. It
      waxes and wanes by successive relapses and remissions. The clinical and
      microscopical diagnosis is complex. In addition to glucagonoma treatments, the
      administration of corticoids, aminoacids, zinc or essential fatty acids can be
      helpful. There exist several etiological hypotheses for NME. These are based on
      modifications of pancreatic enzyme activities and on variations of aminoacids,
      fatty acids, zinc or glucagon concentrations.

PMID- 9927879
TI  - [How I study thyroid pathology using ultrasonography-guided needle biopsy].
AB  - From a retrospective study of 259 files, the authors stress the value of US
      guided thyroid cytoponction and its essential role in case of thyroid cancer
      suspicion. This very specific and inexpensive method fits perfectly into the
      other exploration techniques. It is the deciding factor in the thyroid nodule
      differential diagnostic and therapeutic planning.

PMID- 9927880
TI  - [Essential functions of public health].

PMID- 9927881
TI  - [Epidemic outbreak of dengue virus 2/Jamaica genotype in Bolivia].
AB  - OBJECTIVE: To confirm an epidemic outbreak of Dengue virus in the city of Santa
      Cruz, Bolivia, and to determine the serotype of the virus, to estimate the rate
      of attack and the proportion of symptomatic infections. MATERIAL AND METHODS: In
      March 1997, a seroepidemiological survey was conducted with random sampling in a
      central district of the city of Santa Cruz, Bolivia. Information on recent acute
      illness and febrile episodes was gathered, and venous blood samples were
      obtained. Levels of antidengue IgM were determined by MAC Elisa and the virus was
      typified with RT-PCR. RESULTS: IgM antibodies were detected in 6.5% of adults (CI
      95% 3.4-9.6) and 5.1% of children (CI 95% 2.0-8.2). Circulating virus was
      identified as Dengue serotype 2, subgroup Jamaica. Less than half of the infected
      children experienced a symptomatic infection compared to almost 90% of adults.
      CONCLUSIONS: The estimated attack rates are compatible with a Dengue epidemic
      outbreak in Santa Cruz. The introduction of the serotype 2/ subgroup Jamaica
      virus into the country increases the risk of hemorrhagic Dengue.

PMID- 9927882
TI  - [Folic acid deficiency and its association with neural tube defects in northern
      Mexico].
AB  - OBJECTIVE: To evaluate folic acid deficiency and other risk factors and their
      relationship with the occurrence of neural tube defects (NTD), in the rural
      population of northern Mexico (Chihuahua, Durango and Zacatecas). MATERIAL AND
      METHODS: A multicentric case-control study was performed. Cases were both live
      and stillborn with NTD, and controls were healthy newborns without congenital
      malformations. Exposure to known risk factors was determined, establishing its
      association with NTD using multiple logistic regression analysis. RESULTS: Risk
      factors associated to NTD were: folic acid deficiency (OR 11.1; CI 95% 1.2-106.2,
      p = 0.04); the antecedents of previous NTD pregnancies (OR 3.3; CI 95% 1.1-18.8,
      p = 0.05) and stillbirths (OR 7.1; CI 95% 1.1-46.3, p = 0.04). CONCLUSIONS: Folic
      acid deficiency is one of the major risk factors associated to NTD among the
      rural population of northern Medico. Further investigations are necessary to
      determine the role of involved risk factors and implement adequate preventive
      measures.

PMID- 9927883
TI  - [Prevalence of domestic violence in the city of Durango].
AB  - OBJECTIVE: To characterize and determine the prevalence of the different types of
      gender-associated violence in the city of Durango, Mexico. MATERIAL AND METHODS:
      With a transversal design, 384 women residents of the city of Durango, either
      living with or having lived with someone before, were interviewed. The sample was
      proportionately distributed in 6 city sectors which were randomly chosen and
      representative of the high middle and low socioeconomic levels. Sixty-four
      interviews were conducted in each city sector. The questionnaire consisted of 184
      closed and 22 open questions, including identification, sociodemographic and
      reproductive data, as well as specific questions on physical, emotional and
      sexual violence. RESULTS: Median age of the studied group was 41.5 years, ranging
      from 12 to 48 years. Prevalence of domestic violence was: sexual 42%; physical
      40%; emotional 39%. CONCLUSIONS: The problem of violence, in its different forms,
      is a highly prevalent factor which jeopardizes the welfare of the family nucleus.
      Higher prevalence values of domestic violence were detected in the presence of
      factors such as violence antecedents, alcoholism and/or drug consumption by some
      member of the family.

PMID- 9927884
TI  - [Alcohol consumption patterns in patients admitted to emergency services].
AB  - OBJECTIVE: To describe the alcohol consumption patterns in patients of 15 or more
      years of age, attending the emergency room of 8 possible hospitals in Mexico
      City. MATERIAL AND METHODS: The information was obtained by self-report. Data
      were raised at each hospital for one whole week, 24 hours per day. It includes
      patients who reported alcohol consumption during the 12 months previous to the
      survey. RESULTS: Of the 2,523 interviewed subjects 63% had ingested alcoholic
      beverages, in particular, spirits and beer; 58% admitted having been drunk at
      least once in the past year. The predominating alcohol consumption pattern is low
      frequency and high quantity (46.9%); however, variations were found according to
      sex and age and associated problems are reported. CONCLUSIONS: The description of
      alcohol consumption patterns in different population groups is relevant in the
      study of personal, family and social problems associated to alcohol ingestion.

PMID- 9927885
TI  - [Delivery care in Chiapas, Mexico: who and where does provide it?].
AB  - OBJECTIVE: To identify the place and provider of delivery care; to analyse the
      relationship between the type of delivery care provider and prenatal care and
      sociodemographic factors; to identify groups with greater and lesser probability
      of receiving attention at health centers and to identify the reasons for not
      attending the health center nearest to the household. MATERIAL AND METHODS: Data
      on the delivery care of 297 women of La Fraylesca Region, Chiapas, were gathered
      using multivariate logit models to identify groups. RESULTS: From the total, 32%
      of childbirths occurred at health centers and 60% at home (mostly with poor
      sanitary conditions). Only 10% of women with less than 5 prenatal visits, school
      level under 3 years and whose household head was a peasant were attended by
      health care personnel. CONCLUSIONS: The accessibility and quality of health
      centers must be improved, and a programme aimed at increasing the number of
      deliveries that are attended by trained health care personnel should be
      implemented.

PMID- 9927886
TI  - [Effects of an educational intervention on the quality of life of the
      hypertensive patient].
AB  - OBJECTIVE: To evaluate the effect of an educational program on the quality of
      life of the hypertensive patient. MATERIAL AND METHODS: A randomized clinical
      trial was performed on 150 adult hypertensive patients who were divided into 2
      groups. The experimental group received a short educational program on
      hypertension and the effects on the patients life style, specifically concerning
      their control of the disease. The control group did not receive the educational
      program. Quality of life of both groups was determined by an analogous visual
      scale, before and 6 months after the educational program. Data were analyzed by
      the paired t- and Wilcoxon tests. RESULTS: The degree of improvement with respect
      to physical strength and emotional condition differed between groups (p < 0.05).
      In the areas of thought capacity, social participation, perceived quality of life
      and sexual function only the experimental group showed changes (p < 0.05).
      CONCLUSIONS: An educational program is effective to modify the quality of life of
      the hypertensive patient.

PMID- 9927887
TI  - [Resistance of respiratory and enteral bacteria to antibiotics].

PMID- 9927888
TI  - [Main results of statistics on mortality in Mexico, 1997].

PMID- 9927889
TI  - [The bringing of the latest technology to the evolution of horse shoeing, from
      its origin to our time].

PMID- 9927890
TI  - [The control of epizootics in Switzerland from 1896 to 1996, especially in the
      canton of Lucerne].

PMID- 9927891
TI  - [Study of a portrait of the veterinarian J. J. Seiler from Benken, 1777-1850].

PMID- 9927892
TI  - Thirty ways to lose your lover (or your patients).

PMID- 9927893
TI  - "Been there, done that, didn't like it" (dentistry in England--a lesson in the
      dangers of managed care).

PMID- 9927894
TI  - The Craniofacial Pain Research Unit Mount Sinai Hospital/University of Toronto
      Toronto, Ontario.

PMID- 9927895
TI  - Craniofacial pain: a multidisciplinary approach.
AB  - Patients with pain involving the head and orofacial complex are among the most
      challenging both for dentists and physicians. A collaborative approach to
      diagnosis and management will yield the best possible result for the patient and
      minimize aggravation and frustration for the clinician. This collaboration must
      include ongoing discussion between the various clinicians. Ultimately, the
      various practitioners will develop a deeper comprehension of each others' fields,
      and the boundaries of the various disciplines will become less definite and a
      truly transdisciplinary approach will result. The latter is a highly desirable
      outcome for clinicians and patients. (The patient presenting with an atypical
      facial pain has been used as an example of just such a situation and the brief
      dissertation above should not be interpreted as an in-depth discussion of this
      complex disorder.

PMID- 9927896
TI  - Psychiatric problems in chronic facial pain.
AB  - Facial pain patients have been known to describe their life as "a living hell."
      By employing a biopsychosocial approach, the dental surgeon can often markedly
      reduce suffering and diminish the negative impact of chronic pain on the
      patient's day-to-day life, and enhance his or her capacity to deal long-term with
      this often complex clinical presentation.

PMID- 9927897
TI  - Chronic orofacial muscle pain: a new approach to diagnosis and management.
AB  - The initial data from this study indicate that there are clearly identifiable
      chronic muscle pain conditions in the form of localized pain; myofascial pain or
      regional pain conditions; and fibromyalgia or generalized pain conditions. A
      clear difference exists between the prevalence of these conditions in male and
      female patients, with a higher percentage of female patients suffering
      generalized pain problems and temporomandibular problems. Generalized or
      localized pain appears to be an individual variant of a similar problem and pain
      patients may have a genetically determined vulnerability associated with
      bacterial toxins, particularly within the genitourinary tract. It appears that in
      fibromyalgia there is an underlying genetic factor that causes abnormalities in
      the muscle metabolic cycle, and preliminary data suggest that lipid anomalies
      predispose to fibromyalgia and possibly chronic fatigue syndrome. Patients report
      infectious events at/or around onset in more than 60 percent of cases. Seventy
      percent of fibromyalgic cases report orofacial pain.

PMID- 9927898
TI  - Comorbidity between myofascial pain of the masticatory muscles and fibromyalgia.

PMID- 9927899
TI  - Refractory temporomandibular disorders: understanding and treating the chronic
      facial pain patient.

PMID- 9927900
TI  - Arthroscopy of the temporomandibular joint: a comparison of objective and
      subjective outcome measures in patients with and without evidence of a
      psychopathologic disorder.

PMID- 9927901
TI  - The impact of research on treatment of orofacial pain.

PMID- 9927902
TI  - Relationships between chronic oral infectious diseases and systemic diseases.
AB  - There are over 300 species of bacteria forming populations of several hundred
      billion in the human oral cavity. The number of bacteria reaches a thousand
      billion when the mouth is not sufficiently cleaned. Using saliva and gingival
      crevicular fluid as their main nutrients, these bacteria create their ecological
      niches on tooth surfaces, gingival crevices, saliva, dorsum linguae, and buccal
      and pharyngeal mucosa, threatening oral and systemic health. It is known that
      primary lesions of these chronic bacterial infections secondarily cause
      nephritis, rheumatoid arthritis, and dermatitis. Further, it has been
      demonstrated in recent years that bacteria inhabiting the oral cavity can cause
      bacterial pneumonia and endocarditis and that the periodontal-disease-associated
      bacteria become causative agents for pregnancy troubles and are involved in blood
      circulation problem and coronary heart disease. Dentistry reviewed the theme of
      World Health Day, Oral Health for a Healthy Life, in 1994. The 8020 campaign to
      promote tooth care is also becoming established in Japan; however, the authors
      emphasized that this achievement is not the goal of dental health care. In this
      article, we explain the bases supporting the concept that oral health care,
      primarily mouth cleaning, is important for not only oral disease but also a
      healthy life.

PMID- 9927903
TI  - Relationships between mandibular symphysis morphology and lower incisor
      inclination in skeletal class III malocclusion requiring orthognathic surgery.
AB  - The purpose of this study is to clarify symphysis morphological characteristics
      in skeletal class III malocclusion requiring orthognathic surgery and their
      relationships with symphysis morphology and inclination of the long axis of the
      lower incisor. The materials were pretreatment lateral cephalometric radiographs
      from 50 subjects diagnosed as requiring orthognathic surgery. Controls were 30
      adults with normal occlusion and well-balanced faces. Detailed cephalometric
      measurements on the mandibular symphysis (angular, linear and proportional
      measurements) were recorded and analyzed statistically. In the surgical group,
      the long axis of the lower incisor demonstrated a significant lingual inclination
      in relation to the mandibular plane and symphysis. Moreover, because the
      symphysis demonstrated lingual inclination everywhere except in the basal bone
      region in relation to the mandibular plane, the curvature between the alveolar
      and the basal bone region was significantly smaller than that of normal occlusion
      group. The symphysis labial external surface in the alveolar and basal bone
      regions demonstrated lingual inclination in relation to the mandibular plane,
      however, there was no difference in curvature. Small mean values were obtained
      for Pt.B width, Pog width, and Sym height. Significant differences were observed
      only in Pt.B width. In both the surgical and normal occlusion groups, a
      significant correlation was observed between the inclination of the long axis of
      the lower incisors and symphysis inclination. In the basal bone region, however,
      there was no significant correlation.

PMID- 9927904
TI  - The effects of retraction forces applied to the anterior segment of orthodontic
      arch wires: differences in wire deflection with wire size.
AB  - Orthodontic arch wire deflection was studied in relationship to retraction forces
      applied to arch wires during anterior retraction with sliding mechanics. Two
      different sizes of orthodontic stainless steel arch wires (SS wires) .016" x
      .022" and .019" x .025", were examined. Retraction forces were generated using an
      elastic polymer material to measure arch wire deflection and applied to the arch
      wires by a commonly-used anterior retraction device with power chains hooked from
      the first molar areas to the pre-welded posts at distal site of the lateral
      incisors. The force application caused both the .016" x .022" and the .019" x
      .025" arch wires to deflect. The amount of deflection increased almost in
      proportion to the retraction force applied. With the same retraction force
      applied, the amount of deflection of the .019" x .025" wire was approximately
      47.1% of that of the .016" x .022" wire.

PMID- 9927905
TI  - A clinical analysis of the recovery from sensory disturbance after sagittal
      splitting ramus osteotomy using a Semmes-Weinstein pressure aesthesiometer.
AB  - A number of studies of evaluation methods for sensory disturbance after sagittal
      splitting ramus osteotomy (SSRO) are known. To compare postoperative sensory
      disturbances among patients in different hospitals, a highly reproducible and
      standardized sensory test is required. In the present study, we measured the
      tactile threshold in the region innervated by the mental nerves in 45 patients
      (90 sides) after SSRO using a Semmes-Weinstein pressure aesthesiometer. The
      percentage of recovery to the normal level defined by Bell was 72.2% at one week,
      82.2% at 4 weeks, and 90.0% at 8 weeks after SSRO. The recovery process was
      evaluated by classifying the postoperative sensory disturbance into 5 grade
      levels according to Bell's interpretation scale. The results showed that the SW
      sensory test is useful for evaluation of the recovery process from sensory
      disturbance after SSRO. Some improvements of this test were also discussed.

PMID- 9927906
TI  - Two-dimensional finite element analysis of the influence of bridge design on
      stress distribution in bone tissues surrounding fixtures of osseointegrated
      implants in the lower molar region.
AB  - This study is a comparison and examination of the stress distribution of the bone
      tissues surrounding the fixture under a static vertical load condition with
      regard to an osseointegrated implant bridge (OIB) applied to the lower molar
      region. It was performed by constructing more than one of two-dimensional finite
      element models that differ in design conditions. In the case of the bounded type
      OIB design to the fixture placed in a straight line, a decrease in the maximum
      stress value of the compact bone surrounding the fixture was recognized with a
      decrease in the total inter-fixture distance and an increase in the number of
      placed fixtures. On the other hand, in the case of the free-end type OIB design,
      there is an increase in the maximum stress value compared with the bounded type
      OIB design and, in particular, a marked increase with the decrease in the total
      inter-fixture distance and the extension of the free-end pontic. However, the
      effect of the number of fixtures placed on the maximum stress value of the
      surrounding bone tissues was considered to be comparatively small.

PMID- 9927907
TI  - Central island tongue flap.
AB  - Pedicled tongue flaps have proved to be an effective method of repairing defects
      due to tissue loss in the oral cavity. Their central position, mobility, and
      excellent blood supply make their use feasible in a variety of sites. This paper
      describes the use and applications of central island tongue flaps to reconstruct
      defects of anterior floor of the mouth. This procedure was conducted at the
      Department of Oral and Maxillofacial Surgery, Medical University Hanover,
      introducing an improved surgical method and presenting the actual operation
      performed in our department. This method is considered superior for resurfacing
      the anterior floor of mouth defects because it is easy to perform and results in
      recovery of function and cosmetics.

PMID- 9927908
TI  - Histological study of the healing process of the attachment site of rat masseter
      muscle following injury.
AB  - The masseter muscle functions by attaching itself to the mandible. Thus, it is
      important to study the relationship between the masseter muscle and mandible to
      clarify the complex movement of the jaw. In this study, the chronological changes
      in the attachment site of the masseter muscle to the mandible following injury
      were observed in rats. These findings suggest that, in order for the masseter
      muscle to recover after injury, the tendinous fibers must be repaired, so that
      the entire muscle can be protected and recover functionality to some degree.

PMID- 9927909
TI  - Does advertising render dental research superfluous?

PMID- 9927910
TI  - Failure of oral implants: aetiology, symptoms and influencing factors.
AB  - The use of oral implants opened a wide range of prosthetic treatment
      possibilities in edentulous patients. Although the reported success rates of oral
      implants are high, failures do occur. This paper reviews the current knowledge
      about the aetiology, the signs and symptoms and the possible influencing factors
      of implant failure. Possible causes of implant failure are thought to be
      infection of the periimplant tissues, occlusal overload, or a combination of
      both. Nevertheless, pinpointing one of these as the aetiological factor in a
      particular case is difficult and should be handled reluctantly. Although the
      cause might seem obvious, influencing factors could play a role as well. Gaining
      insight into these processes might stimulate the adoption of preventive action
      and therefore increase the predictability of the treatment outcome with oral
      implants.

PMID- 9927911
TI  - Clinical evaluation of a hybrid composite and a polyacid-modified composite resin
      in Class-II restorations in deciduous molars.
AB  - The aim of this prospective study, conducted in a dental practice was to evaluate
      the success rate of a hybrid composite material (TPH-Spectrum; Dentsply DeTrey,
      Konstanz, Germany) and a polyacid-modified composite resin (Compoglass; Vivadent,
      Schaan, Liechtenstein) in Class II restorations in primary molars after 1 year. A
      total of 190 restorations (96 with TPH-Spectrum and 94 with Compoglass) were
      inserted in 52 children. TPH-Spectrum was applied using the total etching
      technique, whereas Compoglass was inserted without acid etching prior to
      application of the bonding adhesive. The restorations were assessed according to
      the Ryge criteria, directly after placement and after 1 year. After 12 months,
      6.4% of the Compoglass and 3.1% of the TPH-Spectrum restorations were clinically
      unacceptable and had to be renewed. The fillings with Compoglass revealed a
      tendency to lower evaluation scores with respect to color matching, cavosurface
      discoloration, anatomic form, margin integrity and caries assessment than the
      restorations with TPH-Spectrum. However, these differences were statistically not
      significant. The results of the present investigation show that, at least for a
      period of 1 year, both the hybrid composite TPH-Spectrum and the polyacid
      modified composite resin Compoglass are suitable materials for restoration of
      deciduous molars. However, owing to the fewer treatment steps required for
      application of a polyacid-modified composite resin, this type of material may be
      more favorable for restoring primary molars.

PMID- 9927912
TI  - Facial trauma in children and adolescents.
AB  - Most studies on facial trauma in the pediatric age group focus on special
      subgroups. This investigation encompasses all traumatic facial injuries, minor
      and major, of children and adolescents. Epidemiological data of the type and
      pattern of injury of trauma patients less than 19 years of age, treated during a
      3-year-period in a large metropolitan trauma centre were reevaluated. Of the 1385
      patients, 68% had soft tissue injuries, 24% had dental trauma, and 8% fractures
      of facial bones. More than 90% suffered from minimal or minor trauma. The leading
      cause of injury was a fall, predominantly at the toddler stage. In adolescents an
      adult mechanism of trauma prevailed: over 60% of injuries were sequelae of an
      assault or altercation. The male sex predominated through all age groups and for
      all types of injuries. The bulk of soft tissue injuries are located within a
      small falling zone, extending from the nose to the mental area. There was a
      rising incidence of fractures of facial bones towards older age groups,
      mandibular fractures being the most common. Condylar fractures, with their
      potential impact on further growth of the mandible, are seen frequently in
      children and adolescents, making up 80% of the fractures of the lower jaw.

PMID- 9927913
TI  - Mutagenicity of the root canal sealer AHPlus in the Ames test.
AB  - The mutagenic activity of the root canal sealing cement, AHPlus, was tested in a
      bacterial gene mutation assay (Ames test). The material was mixed according to
      the manufacturer's instruction and tested immediately after mixing and after a
      setting time of 24 h at 37 degrees C in a humidified chamber. The set material
      was powdered and both the freshly mixed and the powdered material were eluted in
      dimethyl sulfoxide (DMSO) and physiological saline (0.1 g/2 ml) for 24 h at 37
      degrees C. Aliquots of serially diluted eluates were then used in the standard
      plate incorporation assay. The Salmonella typhimurium tester strains TA98 and
      TA100 were employed to detect the induction of frameshift mutations and base pair
      substitutions both in the presence and in the absence of a metabolically active
      microsomal fraction from rat liver (S9 fraction). No mutagenic and no toxic
      effects were found with physiological saline eluates of the freshly mixed
      material and of mixed material which was set for 24 h. However, DMSO eluates of
      the freshly mixed AHPlus were mutagenic in tester strain TA100 in a dose-related
      manner in the absence of S9. A four- to fivefold increase of the mutation
      frequencies was induced by 2.5 mg AHPlus per plate compared with the number of
      spontaneous mutants. The mutagenic effect was completely abolished in the
      presence of a metabolically active S9 fraction. Also, no mutagenic effects were
      observed with DMSO eluates of AHPlus set for 24 h. However, the set material was
      more toxic towards bacteria than the freshly mixed sealer. This difference was
      indicated by a tenfold lower amount of material necessary to cause complete
      absence of the background lawn in both S. typhimurium tester strains. Therefore,
      we conclude that at least two different compounds of AHPlus are biologically
      active in DMSO eluates to cause mutagenic and toxic effects in S. typhimurium
      TA100 and TA98.

PMID- 9927914
TI  - Effect of multi-step dentin bonding systems and resin-modified glass ionomer
      cement liner on marginal quality of dentin-bonded resin composite Class II
      restorations.
AB  - The use of resin composites in the restoration of Class II cavities with gingival
      margins located in dentin is still controversial. The purpose of this in vitro
      study was to evaluate the effect of four state-of-the-art multi-step dentin
      bonding systems (A. R. T. Bond, Syntac, OptiBond DC, Scotchbond Multipurpose) on
      marginal adaptation and microleakage of dentin-bonded composite Class II
      restorations. A total of 72 Class II cavities with gingival margins in dentin
      were prepared in extracted molars and filled with fine-hybrid composites using a
      three-sited light curing technique. In one half of the cavities the pulpal wall
      was lined with a resin-modified glass ionomer cement liner (RM-GIC), in the other
      half a total bonding technique was applied. A. R. T. Bond and Syntac were tested
      with selective enamel etching (SE) and total etching (TE). Marginal adaptation
      was evaluated in a scanning electron microscope before and after thermocycling
      (TC). Microleakage was determined by dye penetration. After TC the proportions of
      continuous margin in dentin ranged from 37% (Syntac/SE) to 91.2% (A. R. T.
      Bond/TE). Scotchbond Multipurpose exhibited the lowest degree of microleakage
      (0.22 mm). Marginal enamel fracture was the most prevalent marginal defect at the
      enamel margins (8.3-22.2%). The use of the RM-GIC had no beneficial effect on any
      of the marginal parameters, either in dentin or in enamel. It is concluded that
      low degrees of marginal gap formation and microleakage can be achieved in totally
      bonded composite Class II restorations when using state-of-the-art multi-step
      bonding systems in combination with a meticulous incremental filling technique.

PMID- 9927915
TI  - Effect on caries experience of a long-term preventive program for mothers and
      children starting during pregnancy.
AB  - The aim of this three-phase prospective study was to determine the effects of a
      primary-primary prevention program on the oral health of children. Eighty-six
      pregnant women from various social backgrounds participated in the first phase of
      this study. In the second phase (at 3 years of age) 54 of the mother-child
      couples and in the third phase (at 4 years of age) 47 of the mother-child couples
      remained. Participants were recalled every 6 months and received individual
      prophylactic care. The following clinical parameters were assessed at each
      examination period for mother and child: DMF-S or dmf-s, proximal plaque index,
      and the salivary level of Streptococcus mutans (Dentocult SM). The control group
      consisted of 65 (at 3 years of age) and 45 (at 4 years of age) children from
      various kindergartens. All children in the second phase of the study group
      revealed a naturally healthy dentition with an API of 0-25% and a salivary S.
      mutans score of 0 (0-10(3) cfu/ml). In the third phase, only four of the 47
      children of the study group showed caries, with a mean dmf-s of 1.5. No S. mutans
      could be detected in 20 (42.6%) children. Ten (21.3%) children of the study group
      showed a S. mutans score of > or = 2 (> 10(5) cfu/ml). In contrast, only 53 of
      the 65 children of the control group (second phase) and 26 of the 45 control
      children (third phase) revealed a naturally healthy dentition. The remaining 19
      children of the control group revealed a mean dmf-s of 7.0 at 4 years of age. In
      the control group, no S. mutans could be detected in 25 (38.5%) children at 3
      years of age whereas 21 (32.3%) children showed a S. mutans score of > or = 2. In
      the third phase, a salivary S. mutans score of > or = 2 was found in 27 (60%)
      children of the control group. The statistical comparison between the study and
      the control groups revealed significant differences for all results determined (P
      < 0.001). Additionally, all mothers revealed a significant improvement in oral
      health and a reduction of salivary S. mutans colonization. From our data we
      conclude that a pre- and postnatal prevention program (primary-primary vs primary
      prevention) may significantly improve the oral health of mother and child.

PMID- 9927916
TI  - Effects of extraction media upon fluoride release from a resin-modified glass
      ionomer cement.
AB  - Previous studies have shown that various factors such as ionic composition or pH
      of the extraction medium may significantly influence leaching of components from
      restorative materials. Therefore, it was the aim of this investigation to
      determine the release of fluoride from a resin-modified glass-ionomer cement
      (GIC) following storage in various extraction media, including an esterase
      buffer. Specimens of the resin-modified GIC, Fuji II LC, were stored for 144 h in
      deionized water, acidic buffer (pH 4.2), neutral buffer (pH 7.0), and neutral
      buffer supplemented with porcine liver esterase. Fluoride release into the
      various media was measured every 48 h over a 6-day period. In addition, activity
      of porcine esterase in neutral buffer (artificial saliva) was measured for up to
      144 h. The data were statistically evaluated by three-way ANOVA using the Student
      Newman-Keuls test (P < 0.05). It was found that esterase activity in neutral
      artificial saliva decreased during the first 24 h to approximately 40% of the
      baseline value and then remained constant for up to 6 days. Fluoride release into
      the various storage media varied significantly (P < 0.05). The highest amounts of
      fluoride were released into deionized water (30.9 ppm +/- 1.1) and acidic buffer
      (26.9 ppm +/- 0.7) after 48 h. In addition, significantly more fluoride leached
      into esterase-containing neutral artificial saliva (6.9 ppm +/- 0.2) than into
      neutral buffer without enzyme (6.3 ppm +/- 0.2) after 96 h. Our data indicate
      that fluoride release from the resin-modified GIC investigated may be increased
      under acidic conditions and by hydrolysis in saliva.

PMID- 9927917
TI  - The restorative specialties.

PMID- 9927918
TI  - A simple border movement recording device for assessing mandibular mobility.
AB  - A simple border movement recorder, which can be constructed from easily available
      materials, is described. A plotter pen attached to the handle of a lower
      impression tray is used to make a tracing of mandibular opening and closing and
      border movements on a piece of paper attached to a hinged plate mounted on a pair
      of spectacles, gravity holding the paper against the pen. The low cost and ease
      of use of the device may justify its use in cases where temporomandibular joint
      dysfunction is suspected.

PMID- 9927919
TI  - Lifelong education and the dental profession.
AB  - Provision of education is constantly under review, with regular changes to
      address new needs. In addition, demands that cannot be met from within initial
      training courses have spawned a plethora of educational courses to update
      knowledge and develop new skills--in effect promoting lifelong education. The aim
      of this paper is i) to define and explain commonly used educational terms
      relevant to the understanding of lifelong education, ii) to make a distinction
      between lifelong education and continued education, and iii) to offer a rationale
      for the increasing importance of lifelong education for the dental profession.

PMID- 9927920
TI  - In vitro study of fracture strength and marginal adaptation of fibre-reinforced
      composite versus all ceramic fixed partial dentures.
AB  - In this in vitro study fracture strength and marginal adaptation of adhesive
      fixed three-unit posterior fixed partial dentures made with two different
      fabrication modifications--with and without the retainer material "Single"--of
      the new fibreglass system Vectris/Targis and from the metal-free Al2O3-ceramic In
      Ceram were examined. The quality of the marginal adaptation was characterised
      using SEM evaluation and dye penetration techniques. In-Ceram and Vectris/Targis
      with "Single" showed good marginal adaptation, both statistically significantly
      better than the modification without "Single". After thermal cycling and
      mechanical loading the fibreglass reinforced systems showed a significantly
      higher fracture strength than the In-Ceram.

PMID- 9927921
TI  - The significance of major connectors and denture base mucosal contacts on the
      functional strain patterns of maxillary removable partial dentures.
AB  - The purpose of this study was to investigate the biomechanical significance of
      major connectors and base mucosal contacts on the mechanical behaviour of
      maxillary removable partial dentures in vivo. Six subjects wearing maxillary
      dentures retained by conical crowns were selected for the study. Reflective
      photoelasticity and strain gauges were used to monitor the development of
      strain/stress during functional loading. Loading tests were performed initially
      with a denture design including a palatal major connector and denture bases and
      then repeated after removal of the major connectors and denture base alveolar
      muccosa contacts. The palatal major connector and the denture bases mucosal
      contacts contribute significantly to the rigidity and stability of removable
      partial dentures retained by conical crowns.

PMID- 9927922
TI  - Impression materials and techniques for crown and bridgework: a survey of
      undergraduate teaching in the UK.
AB  - The aim of this study was to document the teaching of impression materials and
      techniques for crown and bridgework in the undergraduate curriculum in UK dental
      schools. A questionnaire sent to each school during the 1993/1994 academic year
      elicited fourteen replies (100% response). Addition-cured silicones were found to
      predominate; 71% of schools taught and used clinically a one-stage, full arch
      impression technique involving stock trays, and 57% of schools a full-arch custom
      tray technique. Routine disinfection of impressions was taught and practised in
      43% of schools. The results demonstrated variation between UK dental schools in
      their teaching of impression materials and techniques for crown and bridgework in
      the undergraduate curriculum.

PMID- 9927923
TI  - Weight and linear dimensional changes of reversible hydrocolloid duplicating
      materials: effect of storage and re-use.
AB  - Weight and linear dimensional changes of two hydrocolloid duplicating materials
      following setting in various environments were examined. Prior to the
      measurements, the sample materials were stored either in the sol or in the gel
      phase, for a period of 5 days, in order to evaluate the effect of ageing on their
      composition and behaviour. A 100% relative humidity environment produced the
      least change to the set material, and in this environment, the behaviour of the
      materials was not affected by their age. Results indicate that deterioration of
      the duplicating materials provoked by repeated or prolonged heating, is
      detectable, through their weight changes, even at an early stage.

PMID- 9927924
TI  - Whither paediatric dentistry?
AB  - The objective of the British Society of Paediatric Dentistry is to promote the
      oral health of children. This objective is discussed from four different aspects.
      First, it is necessary to quantify the dental needs of children and to appreciate
      how these needs have changed over the last 20 years. Using information from
      national dental surveys, changes between 1973 and 1993 in the prevalence of
      dental caries, periodontal disease, accidental damage to anterior teeth and
      occlusal problems, are summarized. Secondly, the development in consultant posts
      and the specialty of paediatric dentistry are discussed. The impact of research
      gradings given to Dental Schools in Britain is the third aspect to be considered
      and its possible effect on research topics directly relevant to improving the
      oral health of children. Lastly the effect of public perceptions on our specialty
      must be considered. Although paediatric dentists may not hit the headlines, the
      public must be convinced that good oral health is the birthright of every child
      and that we are dedicated to preventing and treating oral disease in children.

PMID- 9927925
TI  - The chronology and sequence of eruption of human permanent teeth in Northern
      Ireland.
AB  - OBJECTIVES: To ascertain the average and range of ages and sequence of eruption
      of human permanent teeth, taking into account the effect of premature loss of
      primary antecedents. DESIGN: Longitudinal study. SETTING: Caucasian subjects in
      Northern Ireland. SAMPLE AND METHODS: Study casts at 6-monthly intervals from age
      5 to 15 years of 276 children (146 males and 130 females) enrolled in the Belfast
      Growth Study. The mean and range of ages of eruption of each individual tooth
      were computed. Comparisons were made between the mean ages of eruption with and
      without premature loss of primary antecedents, between upper and lower arches,
      between right and left sides and between males and females. The sequence of
      eruption was also investigated. RESULTS: The means and ranges of eruption ages
      are reported. Premature loss of primary antecedents delayed eruption of permanent
      successors except for the upper premolars which were accelerated. The differences
      relating to the upper first premolar and lower canine were not statistically
      significant. Each lower tooth erupted before its upper counterpart except for the
      premolars. There was no significant difference in age of eruption between right
      and left sides. Females tended to erupt teeth before males with the exception of
      the second molars in both arches; however, the only differences to reach
      statistical significance related to upper and lower canines and upper lateral
      incisors. The most frequent orders of eruption were unique to the subject. These
      occurred in 22% of upper and 33% of lower arches. The classic sequences: first
      molar-central incisor-lateral incisor-first premolar-canine-second premolar
      second molar (M1-I1-I2-PM1-C-PM2-M2) in the upper arch and I1-M1-I2-C-PM1-PM2-M2
      in the lower arch occurred in only 16% of upper arches and 13% of lower arches.
      Males adhered to the textbook sequence (20% upper, 17% lower) more than females
      (12% upper, 8% lower). In the upper arch of females, the order M1-I1-I2-PM1-PM2-C
      M2 in 10% of subjects was almost as frequent as the classic sequence. CONCLUSION:
      The ages, ranges and orders of eruption found in this study are more reliable
      than many which are frequently quoted on account of its longitudinal nature and
      the fact that the effect of premature loss of primary antecedents is taken into
      account. The exclusively Caucasian sample makes the data quite precise but limits
      applicability to patients of this ethnic origin.

PMID- 9927926
TI  - Arresting dentine caries in Chinese preschool children.
AB  - OBJECTIVES: To investigate the incidence of rehardening of caries lesions in
      children in Southern China taking part in a preventive programme. DESIGN:
      Longitudinal study. SAMPLE AND METHODS: A prevention programme was established
      for 168 3-6-year-old children in a kindergarten (KG1), which included regular
      oral health education sessions and a daily toothbrushing exercise using
      fluoridated toothpaste (1000 ppm F). A group of 121 children studying in two
      other kindergartens without a preventive programme formed the controls. Due to
      lack of resources and dental personnel, restorative and other curative treatments
      were not provided. RESULTS: Rehardening of dentine caries (arrested caries) was
      found in children in both test and control groups. At the third annual
      examination, 45% of the caries lesions on the proximal surfaces of primary
      anterior teeth in KG1 children found at the baseline and previous annual
      examinations had become arrested. A multiple linear regression analysis indicated
      that baseline ds score and its interactions with the prevention programme, gender
      and the child's oral hygiene all had significant effect on the number of tooth
      surfaces with arrested caries at the third annual examination. CONCLUSION:
      Results from this study support the use of simple prevention programmes to
      stabilize the caries situation in communities where intensive use of trained
      dental personnel is not feasible.

PMID- 9927927
TI  - Relationship between mothers' gingival condition and caries experience of their 3
      year-old children.
AB  - OBJECTIVES: The main aim of this study was to investigate the relationship
      between mothers' gingival condition (an assumed indicator of their self-care
      level) and the prevalence and severity of dental caries of their children. SAMPLE
      AND METHODS: Subjects comprised 1471 pairs of mothers and their children who
      attended for the 3-year-old dental check-up at a community health centre in
      Hiroshima. The mothers' gingival condition was scored as 'excellent (+2)', 'good
      (+1)', 'questionable (0)', 'poor (-1)' or 'very poor (-2)' according to the
      criteria of the Oral Rating Index (ORI). Caries experience of the children was
      recorded using the WHO caries diagnostic criteria for dmft. RESULTS: The
      percentage of caries-free children was 51.3%, and the mean dmft score was 2.61.
      The percentages of caries-free were higher and the mean dmft level were lower in
      the children of mothers with better gingival condition compared to the children
      of mothers with worse gingival condition. CONCLUSIONS: Mothers' gingival
      condition was associated with the prevalence and severity of dental caries of
      their children.

PMID- 9927928
TI  - A repeated criterion-based audit of radiographic usage by a paediatric dentistry
      unit.
AB  - AIMS: To report a simple clinical audit which was conducted within a single
      hospital paediatric dental unit and to demonstrate the potential value of such
      small-scale projects. DESIGN: A criterion-based audit of radiographic practice
      which was repeated after 3 years in order to evaluate changes. SETTING: Six 1
      hour meetings of an audit group consisting of the staff and postgraduate students
      of the Unit. SAMPLE AND METHODS: Various aspects of radiographic usage were
      quantitatively assessed using a sample of patient records and a pre-planned check
      list to assess the extent to which agreed good-practice criteria were being met.
      The initial audit identified areas for improvement which were addressed before
      repeating the exercise 3 years later. RESULTS: Clinical note-keeping to accompany
      radiographic examinations was found to be the least satisfactory area of
      practice. When the exercise was repeated, encouraging improvements were
      demonstrated. CONCLUSIONS: The audit was worthwhile because it appeared to
      produce improvements in standards of patient care.

PMID- 9927929
TI  - Cysticercosis of the oral cavity: report of five cases and a review of
      literature.
AB  - This paper reports on five cases of cysticercosis of tongue and buccal mucosa,
      diagnosed on fine-needle aspiration cytology (FNAC), affecting child patients who
      presented between January 1994 and October 1997. Four cases presented with
      gradually increasing nodular swelling of the dorsum of tongue and in the fifth
      case the swelling was situated on the buccal mucosa of the left side. A clinical
      diagnosis of cysticercosis was not entertained in any of these patients, who each
      presented with a solitary lesion; instead, it was considered to be a benign cyst
      or benign tumour of salivary gland or mesenchymal tissue, before FNAC diagnosis.
      These lesions of the oral cavity may present first to a dentist and, in endemic
      areas, cysticercosis should be included in the differential diagnosis of solitary
      nodular lesions of the oral cavity, particularly in young individuals.

PMID- 9927930
TI  - A four-rooted primary upper second molar.
AB  - Both primary upper second molars were extracted from a young male patient. The
      left had a normal root pattern but the right had four well-defined roots. The
      accessory root appeared to be the mesiopalatal which had a distinctly rounded
      cross-sectional profile. The other roots had the typical form characteristic of
      primary molar roots. Some degree of bifurcation can occur in the mesiobuccal
      roots of upper molars and the accessory root described in this report may
      represent an extreme example of such bifurcation.

PMID- 9927931
TI  - Peri-radicular inflammation related to dens invaginatus treated without damaging
      the dental pulp: a case report.
AB  - A 12-year-old boy was referred with a discharging sinus tract related to the
      maxillary left lateral incisor, and with a non-vital maxillary left central
      incisor. The lateral incisor gave a positive response to sensitivity testing. The
      lesion did not heal after disinfection of the root canal of the central incisor,
      but healed subsequently after 'endodontic' treatment of an invagination in the
      lateral incisor. After 2 years the lateral incisor continued to give a positive
      response to sensitivity testing.

PMID- 9927932
TI  - UK National Clinical Guidelines in Paediatric Dentistry. Management and root
      canal treatment of non-vital immature permanent incisor teeth. Faculty of Dental
      Surgery, Royal College of Surgeons.

PMID- 9927933
TI  - Practising through the changes: a personal history of SAAD.

PMID- 9927934
TI  - Topics in medicine: asthma.

PMID- 9927935
TI  - The myoepithelium of human major salivary glands revisited.
AB  - The presence of myoepithelial cells in salivary glands is of importance with
      regard to tumour histogenesis, yet there is no consensus in the literature as to
      the specific location of these cells. A major problem has been the methods of
      precise identification of myoepithelium at the light microscopic level. The
      present study therefore reviews the distribution of myoepithelial cells in the
      major salivary glands (parotid, submandibular and sublingual) of the human,
      utilising a monoclonal antibody specific to actin, a cytoplasmic component of the
      myoepithelial cell. Qualitative analysis was performed to assess the distribution
      of these cells in mucous and serous acini and in the different regions of the
      ductal system. As previously described, myoepithelial cells were found to be
      present around serous and mucous acini as well as the intercalated ducts of all
      the major glands. They appeared to be more abundant in mucous than in serous
      acini of the submandibular and sublingual glands. In addition, this study has
      demonstrated the presence of myoepithelial cells in the proximal portion of
      striated ducts in the submandibular gland--a location that has not previously
      been reported in the human.

PMID- 9927936
TI  - The film thickness of five adhesive resin cements.
AB  - The purpose of this in vitro investigation was to determine the film thickness of
      five resin cements, namely All-Bond 2(Bisco,AB), C&B-Metabond(Parkell,CB),
      Enforce(Caulk/Dentsply,E), Imperva Dual(Shofu,ID) and Panavia EX(Kuraray,P). An
      electronic gauge with an accuracy of 0.5 micron was recalibrated after each
      recording, and each cement was measured 10 times. Statistical analysis was
      carried out using the ANOVA test. The mean film thickness values (micron) of the
      five cements were: AB = 58.8 +/- 4; CB = 35.8 +/- 1.2; E = 22.9 +/- 1.4; ID =
      25.7 +/- 1.2 and P = 44.3 +/- 1.2. There was a statistical significant difference
      between the film thicknesses of AB and the other cements (p < 0.05). The ID and E
      cements also demonstrated statistically significant lower film thicknesses than
      CB and P (p < 0.01). Imperva Dual and Enforce demonstrated the lowest and All
      Bond 2 the highest film thickness values.

PMID- 9927937
TI  - The Graduate: newsletter of the HSRC.

PMID- 9927938
TI  - The epidemiology of malocclusion in Zambian urban school children.
AB  - This survey was undertaken to determine the occlusal status of a selected group
      of urban Zambian Black 9-12 year old children at 5 different schools in the same
      geographical area in order to determine their need for orthodontic treatment. The
      examination criteria of the Occlusal Index of Summers (1966) were used. Six
      hundred and one children who had not previously received orthodontic treatment
      were examined. The data were analysed statistically by using the calculated
      Summers Index. The results showed that 83 per cent of the subjects required no
      orthodontic treatment. Of the 17 per cent who did require orthodontic treatment,
      5.2 per cent needed specialized treatment. The malocclusion status of Black
      Zambian children is very similar to that recorded in epidemiological studies on
      South African and Swazi Black children. This study indicates that only a small
      need exists for orthodontic treatment amongst Black Zambian children.

PMID- 9927939
TI  - Regional urban-rural distribution of dental caries experience in Swaziland.
AB  - Understanding the regional and countrywide urban-rural distribution of dental
      caries in Swaziland was considered important for the formulation of a National
      Oral Health Policy based on the Primary Health Care Approach. A National Oral
      Health survey was undertaken in Swaziland at the request of the ministry of
      health. Part of the objective of this study was to establish the regional urban
      rural distribution of dental caries in Swaziland. For the 6-18 year olds a
      cluster sampling technique by schools was used to get a representative sample.
      For the 35-44 year age group a simple random sampling technique was used in areas
      of employment influenced by regional and urban-rural distribution. All
      examinations were carried out using the WHO 1987 criteria. More than 90 per cent
      of the mean dmft of 6 and 12 year olds was comprised of the decayed component of
      the dmft/DMFT. The level of restorative care (ft/dmft, FT/DMFT) was low for all
      age groups. For the 6 and 12 year olds in the Lubombo region there was a
      significant difference (p < 0.05) in the urban-rural caries experience. When
      regional data for 6 and 12 year olds were pooled, the difference in urban-rural
      caries experience is also significant (p < 0.05). For the older age groups there
      was no significant difference (p > 0.05) in the regional urban-rural caries
      experience. This study indicates that the oral health care system in Swaziland
      with its limited resources, should focus its attention on the younger age groups
      especially in urban areas as far as dental caries treatment needs and preventive
      programmes are concerned.

PMID- 9927940
TI  - Anterior and posterior temporaries, speed formed and bonded.

PMID- 9927941
TI  - Pre-authorisation: no guarantee of payment.

PMID- 9927942
TI  - Perio study findings clarified.

PMID- 9927943
TI  - The new toothpastes.

PMID- 9927944
TI  - Planning your practice: what's the bottom line?

PMID- 9927945
TI  - Direct reimbursement benefit plans can benefit everyone.

PMID- 9927947
TI  - Choosing technology.

PMID- 9927946
TI  - Disability insurance: a new era.

PMID- 9927949
TI  - Computerization is not the solution in itself.

PMID- 9927948
TI  - The 1998 TDA membership survey.

PMID- 9927950
TI  - Selecting office management computer equipment.
AB  - Even though you will never find a dental management system that will do exactly
      what you want, there are a tremendous variety of systems out there with some
      incredibly powerful features. Look for a system that can handle most of the tasks
      you need. Keep your eye on other technologies that you may want in your practice.
      The system you purchase now should be able to handle whatever technologies you
      decide to add on in the next 3 to 4 years. Once you have made the decision to
      purchase, the transition to automated management begins. It will be necessary to
      train you and your staff on how to use the system. Depending on the system
      chosen, it may be necessary to adjust your management strategies in a number of
      areas to take advantage of the system's features. This may cause a few adjustment
      problems at first, but things will work out with a little time and effort. In the
      next few years, advances in technology integration will allow you to seamlessly
      blend practice management, voice charting, intraoral cameras, CAD/CAM, lasers,
      EDI, video imaging, etc., into a single potent system for complete clinical and
      practice management. A dental practice management system is the first step to
      realizing that future. Shop wisely and invest your time in learning the
      terminology and techniques of automated information management.

PMID- 9927952
TI  - The Internet: A risk management perspective.

PMID- 9927951
TI  - Practice management applications.

PMID- 9927953
TI  - Dentists and dental lab technicians: are you writing your laboratory
      prescriptions and work orders properly?

PMID- 9927955
TI  - Workers' compensation insurance: protect yourself, protect your practice.

PMID- 9927954
TI  - Impact of HIV on the practice of dentistry in Houston, Texas.
AB  - Texas ranks fourth in the nation in the number of documented HIV-infected and
      AIDS cases. The city of Houston has the highest prevalence of HIV-infected and
      AIDS cases in Texas. Dental health personnel have an ethical and legal obligation
      to provide dental services for HIV-infected persons. The purpose of this study
      was to assess the impact of HIV on the practice of dentistry in Houston. The
      study population was all dentists with a current Houston practice address
      registered with the Texas State Dental Board. A 41-item questionnaire was mailed
      to a stratified random sample of 500 dentists in Houston. The questionnaire
      covered four main areas: demographics, knowledge, attitudes, and behavior. About
      three-quarters of the dentists said they had treated an AIDS or HIV+ patient.
      Sixty percent of the dentists were not aware that breastmilk is a mode of
      transmission of HIV. There was a significant correlation between "ever treated"
      an HIV+ patients and "willingness to treat" an AIDS or HIV+ patient (p < 0.01).
      The experience of treating HIV-infected patients has a greater impact than
      knowledge alone in influencing dentists' behavior towards AIDS/HIV+ patients.

PMID- 9927956
TI  - The stuffy nose and rhinitis.
AB  - The congested nose may represent a mild nuisance or be indicative of a serious
      health condition. Familiarity with appropriate methods of evaluation and testing
      can help avoid diagnostic pitfalls and make an accurate, timely assessment of the
      patient's condition.

PMID- 9927957
TI  - Evaluation and management of allergic rhinitis.
AB  - Allergic rhinitis is a problematic disorder that is common. The practicing
      physician recognizes the majority of the overt clinical symptoms of sneezing,
      nasal itching, postnasal discharge, and eye symptoms but may not be attuned to
      the more subtle symptoms of lethargy, headache, and loss of productivity they
      create. Food sensitivities may complicate the evaluation and treatment of the
      sensitive patient, and frequently the idea of foods causing problems with
      rhinitis is ignored. For most patients, practical medications are beneficial in
      reducing symptoms without producing the side effects of sedation. The newer
      topical nasal steroids are becoming the first line of therapy, and nonsedating
      antihistamines are still useful because they have few side effects. Immunotherapy
      is recommended for treatment failures in the appropriate patient. Specialty
      referral then should be considered.

PMID- 9927958
TI  - Rhinosinusitis. Current concepts in evaluation and management.
AB  - Sinusitis is one of the most common health complaints leading to a physician
      office visit in the United States. Recently standardized terminology with
      diagnostic parameters are outlined. Following this is a detailed discussion of
      the basics of relevant history and physical examinations, laboratory and
      radiology testing, the appropriate selection of pharmacotherapy, and the
      indications for surgical intervention.

PMID- 9927959
TI  - Epistaxis.
AB  - Epistaxis is a common clinical problem. The widespread availability of endoscopic
      equipment is shifting management philosophy toward targeting the bleeding point.
      This shift may have a significant impact on decreasing length of stay and blood
      transfusion rates. Advances in interventional radiology have also reduced the
      risk of embolization. Patient education, especially teaching first-aid measures
      to patients at high risk for nosebleeds, also encourages more effective use of
      health care resources.

PMID- 9927960
TI  - Disorders of smell and taste.
AB  - As with almost any aspect of medical practice, a thorough history and physical
      examination coupled with a good understanding of the anatomy and physiology of an
      organ system are the key factors in reaching a diagnosis. The information in this
      article is provided to assist the internist with the diagnosis of chemosensory
      disorders and the differentiation of malingering or other disease process as well
      as providing insight into the workup, prognosis, and treatment of patients with
      taste and smell disorders.

PMID- 9927961
TI  - Sore throat, tonsillitis, and adenoiditis.
AB  - Diseases of the adenoids and tonsils are a frequent cause for patients to seek
      medical attention. A thorough understanding of the disease processes reflected in
      the adenoids and tonsils and their diagnosis and treatment is an important part
      of routine care delivery. Diagnostic methodologies and timing of surgical
      intervention are reviewed along with general considerations relating to the
      differential diagnosis in adult and pediatric patients.

PMID- 9927962
TI  - Snoring, obstructive sleep apnea, and surgery.
AB  - Snoring and OSA syndrome are prevalent and important causes of sleep disturbance.
      Snoring, historically considered to be only a habitual annoyance, has significant
      physical and social consequences. OSA is now considered to be a major public
      health concern with significant morbidity and mortality. CPAP is considered the
      treatment of choice for OSA syndrome, but poor patient acceptance and compliance
      remain problematic. Surgical procedures have been developed to alter the
      offending anatomic abnormalities responsible for OSA. Identification of the
      offending anatomic site with application of the most appropriate surgical
      procedure is essential for effective surgical treatment of OSA. When the region
      of the retropalate is correctly identified as the site of obstruction, UPPP can
      effectively treat OSA in a majority of patients. Surgical correction of nasal
      obstruction is advocated in conjunction with sleep apnea surgery when nasal
      obstruction exists. In OSA patients with retrolingual airway obstruction, a
      number of surgical procedures have been performed, with or without UPPP, with
      some improvement over UPPP alone. MMO has been effective in the treatment of OSA
      in patients with significant retrolingual airway obstruction with contributing
      skeletal abnormalities and in patients who have failed multiple other surgical
      procedures. MMO, however, is a procedure of considerable magnitude, requiring
      extensive oromaxillofacial surgical expertise. MMO is likely appropriate only in
      a limited number of patients. Tracheostomy is completely effective in the
      treatment of OSA syndrome but is undesirable to patients and is associated with
      significant physical and emotional morbidity. Nonetheless, tracheostomy can be
      lifesaving and remains an option for patients with severe OSA with serious
      associated cardiovascular complications, who cannot tolerate CPAP, and for whom
      other interventions are ineffective or unacceptable. Effective surgical treatment
      of snoring has been accomplished with UPPP and LAUP. LAUP is less invasive, less
      morbid, more cost-effective, and better tolerated and is likely the most
      appropriate procedure for debilitating symptomatic snoring. Currently, LAUP is
      not recommended for the treatment of OSA, despite some efficacy in patients with
      mild OSA. Exclusion of OSA in patients undergoing LAUP for snoring is important.

PMID- 9927963
TI  - Swallowing disorders.
AB  - Swallowing disorders affect a large and growing number of people in the United
      States, particularly the elderly. An appreciation of the anatomy, physiology and
      pathophysiology of swallowing disorders allows the practitioner to assess these
      problems and to make arrangements for their treatment. The purpose of this
      article, therefore, is to give an overview of the diagnosis and treatment of
      swallowing disorders.

PMID- 9927964
TI  - Hoarseness.
AB  - The voice is the primary means of communication for humans socially and in the
      workplace. Although rarely life-threatening, voice problems cause tremendous
      alteration in daily living and should not be underestimated as a medical
      disorder. Besides affecting useful communication, voice problems may also signify
      the presence of more serious medical illnesses, such as malignancy or airway
      compromise. This article describes normal vocal anatomy and physiology and
      outlines a practical approach in evaluating patients with voice disorders.

PMID- 9927965
TI  - Hearing loss.
AB  - Hearing loss may be caused by either a conductive problem, such that the sound
      waves do not reach the tympanic membrane, ossicles or inner ear, or a
      sensorineural problem, in which the cochlea and/or auditory nerve are somehow
      damaged. A combination of the above may also occur. The various causes of hearing
      loss and the options in treatment will be presented.

PMID- 9927966
TI  - Hearing aids.
AB  - The first step in the hearing aid fitting and selection process is to determine
      the patient's hearing disability, motivation, lifestyle, finances, and cosmetic
      concerns. Most hearing impairments can be helped with a modern hearing aid. With
      a symmetric hearing loss, a binaural fitting provides the most benefit and should
      be attempted initially. The binaural fitting may not be successful in cases with
      large asymmetries in auditory function. The advances in electronic technology,
      such as the digital hearing aid, are moving faster than the research to determine
      which is the most effective signal processing method. The near future should
      yield more significant improvements in hearing aids that will provide a better
      quality of life of the hearing-impaired population.

PMID- 9927967
TI  - Tinnitus. Current evaluation and management.
AB  - Evaluation and management of tinnitus presents a significant challenge to the
      internist and the otolaryngologist. Tinnitus may be divided into two basic
      categories: subjective and objective. The importance of a thorough history and
      physical examination is emphasized in this article. The steps in a complete
      evaluation and the rationale for referral to an otolaryngologist are outlined.
      Multidisciplinary care of the tinnitus patient is best coordinated by the
      otolaryngologist.

PMID- 9927968
TI  - The diagnosis and treatment of dizziness.
AB  - Dizziness is a complex and frustrating symptom of potentially numerous causes.
      The history and physical examination can elicit the category that best
      characterizes the dizziness: vertigo, presyncope, dysequilibrium, or
      lightheadedness. If the cause of dizziness cannot be found or treated directly,
      medications may suppress symptoms. Surgery for vertigo includes conservative and
      destructive procedures. Rehabilitation is often a useful adjunct in the treatment
      of many types of dizziness.

PMID- 9927969
TI  - The facial nerve. Current trends in diagnosis, treatment, and rehabilitation.
AB  - Facial paralysis is a potentially devastating disorder with numerous
      implications. Multiple entities must be considered in its etiology, and recent
      advances in microbiology, radiographic imaging, electrodiagnostic testing, and
      microsurgery have provided great insight into the pathophysiology, diagnosis,
      treatment, and rehabilitation of the facial nerve. Recent DNA PCR testing has
      shed new insight into the potential cause for Bell's palsy. This article focuses
      on the evaluation, differential diagnosis, medical treatment, and rehabilitation
      of facial nerve pathology with primary emphasis on facial paralysis. Surgical
      management is also discussed, including reanimation of the paralyzed face.

PMID- 9927970
TI  - Salivary gland disorders. Neoplastic and nonneoplastic.
AB  - This article reviews the common inflammatory and neoplastic diseases that afflict
      the salivary glands. The general presentation, pathology, and treatment of each
      is discussed.

PMID- 9927972
TI  - Current options in management of head and neck cancer patients.
AB  - Head and neck cancer, particularly squamous cell carcinoma (SCC) of the upper
      aerodigestive tract, poses difficult diagnostic and therapeutic challenges to the
      clinician. A methodical approach, including complete visualization of mucosal
      surfaces, appropriate imaging, and tissue diagnosis whenever possible, gives
      patients the best opportunity for early intervention. A treatment program of
      surgery, radiation, or chemotherapy is best developed by a devoted head and neck
      oncologic team, involving surgeons, radiation and medical oncologists, and
      rehabilitative specialists with significant experience in the care of head and
      neck oncologic patients. Despite new advancements in the treatment of patients
      with advanced stage SCC of the head and neck, little progress has been made in
      overall survival. Several new avenues of investigation are currently being
      explored, one of which may ultimately provide the answer for this devastating
      disease.

PMID- 9927971
TI  - The neck mass.
AB  - Many head and neck disease processes are manifest as neck masses. These
      conditions are treated by surgical excision except for some inflammatory masses,
      and often those too must be excised before a diagnosis can be made. The real
      question is when to excise the lesion to expedite treatment in the most cost
      effective manner. In general, when signs of inflammation are associated with the
      mass, antibiotic treatment with short-term observation is acceptable. Persistence
      of the mass or an increase in mass size during observation mandates for their
      evaluation. Biopsy of a mass is considered for progressive growth, isolated
      nature or asymmetry of the mass, location (supraclavicular), development of
      symptoms associated with lymphoma (fever and hypertrophy of the spleen, liver, or
      Waldeyer's ring), or static size (if > 3 cm). In the adult patient, a complete
      head and neck physical examination is mandatory before biopsy. Needle biopsy of
      the neck mass is the current standard of care if no cause of the mass is found on
      examination. Identified benign cystic lesions or lymphomas indicate a need for
      excision, either as definitive treatment or for diagnostic reasons. If results of
      the needle biopsy are positive, equivocal, or even negative in the presence of a
      high index of suspicion for metastatic squamous cell carcinoma, an endoscopic
      examination is mandatory before open excision. If no discrete lesion is seen,
      guided biopsy of the upper aerodigestive tract is performed. Open biopsy of the
      mass should be accompanied by a frozen-section examination of the mass. A
      concomitant definitive neck dissection should be performed if the mass proves to
      be metastatic carcinoma.

PMID- 9927973
TI  - Surgical management of thyroid and parathyroid disorders.
AB  - This article begins with a discussion of thyroid anatomy and physiology and then
      proceeds with an in-depth study of the area of focus, thyroid and parathyroid
      disorders, including thyroid nodules and cancer, multinodular goiter, and
      hyperparathyroidism. Complications of thyroid and parathyroid surgery are
      discussed.

PMID- 9927974
TI  - Skin cancer of the head and neck.
AB  - The incidence of skin cancers is increasing at a rate greater than any other
      cancer occurring in humans. In this era of managed care, patients with a
      suspicious skin lesion may first present to their primary care physician for
      evaluation. Therefore, it is important for the primary care physician to be able
      to distinguish between benign and malignant pigmented lesions, to know how to
      evaluate such a patient, and to appreciate the importance of appropriate
      interdisciplinary management of these patients.

PMID- 9927975
TI  - Options in the management of the aging face. An otolaryngology-facial plastic and
      reconstructive surgeon's perspective.
AB  - Our objective is to keep the discussion relevant to internists and primary care
      providers. The presentation, evaluation, and management of the most common
      manifestations of the aging face are included. For organization and analytical
      purposes, the aging face is divided into thirds. Each procedure described
      addresses one segment of the aging face. Rejuvenation of the brow and eyelids,
      correction of facial rhytids (wrinkles), and resurfacing of fine-line wrinkles
      are all covered in this article.

PMID- 9927976
TI  - Otolaryngologic manifestations of human immunodeficiency virus infection.
AB  - Patients infected with HIV have become a steadily increasing part of most medical
      practices. Because most patients with HIV-related problems have manifestations in
      the head and neck, it is important that these be understood and recognized. This
      article briefly reviews the various otolaryngologic manifestations of HIV
      infection, including otologic, nasal, and paranasal sinus; oral cavity, pharynx,
      and larynx; and the neck.

PMID- 9927977
TI  - A selective history of groin hernia surgery in the early 19th century. The
      anatomic atlases of Astley Cooper, Franz Hesselbach, Antonio Scarpa, and Jules
      Germain Cloquet.
AB  - One of the most important eras in the evolution of groin hernia surgery is that
      of the early 19th century. It was a time when cadaver dissections and diverse
      clinical studies culminated in a more thorough anatomic understanding of the
      inguinal canal. For reasons cloaked in permanent historical uncertainty, the
      style of hernia textbook publishing also dramatically changed at the turn of the
      19th century when sumptuous anatomical atlases, exemplified by those of Astley
      Cooper, Franz Hesselbach, Antonio Scarpa, and Jules-Germain Cloquet, began to
      appear. Characterized by the presence of numerous detailed engravings these texts
      were expensive to publish and often had limited print runs. The publishing
      history and clinical impact of these now rare hernia tomes are analyzed in this
      article.

PMID- 9927978
TI  - Epidemiologic, economic, and sociologic aspects of hernia surgery in the United
      States in the 1990s.
AB  - Such important, yet basic, questions as the percentage chance that an individual
      will over the course of his or her life be in need of or actually undergo a groin
      herniorrhaphy or the absolute number and type of hernias that exist in a given
      society on any particular day continue to be statistically undefined. A review of
      epidemiologic data provides come preliminary answers. Recent studies from the
      National Center for Health Statistics show that approximately 750,000 groin
      herniorrhaphies are completed annually in the United States. More than 80% of
      these operations involve the use of mesh prosthesis and are performed on an
      outpatient basis. Despite the large number of hernioplasties completed, the
      public's understanding of hernias and their management remains unsophisticated.

PMID- 9927979
TI  - Etiology and pathophysiology of primary and recurrent groin hernia formation.
AB  - The cause of primary groin hernia is multifactorial with evolutionary,
      hereditary, congenital, environmental aspects, and the general state of health
      all playing their part. Besides maintaining general body fitness and not smoking
      tobacco, there is little one can do to avoid this common affliction. On the other
      hand, recurrent groin hernia is largely due to easily controllable human factors
      and can be avoided by choosing an experienced surgeon with a particular interest
      and understanding of the subject, preferably one who specializes in and confines
      himself to the surgery of groin hernias, working in a unit dedicated to
      herniology he will select the best operation for the particular type of hernia
      and execute it to conform to the highest acceptable standards, using the best
      materials and techniques. The patient will rapidly, within a matter of days,
      return to his full, normal activities and can look forward to a success rate of
      over 99%.

PMID- 9927980
TI  - The historical development of prosthetics in hernia surgery.
AB  - Since the time of Bassini, surgeons have looked for techniques and applicable
      prostheses to improve the results of hernia surgery. This article records the
      historical parade of biomaterials used in this endeavor from the earliest use of
      sliver wire coils to the current popular prostheses in use today, each prosthesis
      is reviewed with respect to its introduction, popularization, clinical use, and
      ultimate failure. Current prosthetic biomaterials are compared in detail. The
      quest for the ideal material to reinforce or bridge abdominal wall defects is
      discussed.

PMID- 9927981
TI  - Mesh plug repair and groin hernia surgery.
AB  - Since the mid-1980s, dramatic progress has been made in the evolution of hernia
      surgery, highlighted by the increasing use of prosthetic mesh. Among the mesh
      based "tension-free" hernioplasties, the use of mesh plugs has garnered a large
      number of spirited enthusiasts, and plug herniorrhaphy has become the fastest
      growing hernia repair currently employed by the American surgeon. To demonstrate
      the simplicity and effectiveness of mesh plugs, a 9-year experience with almost
      3300 patients is reported. Technical details are discussed and presentation of a
      literature search serves to further emphasize the utilitarian nature of this
      elegantly unsophisticated surgical operation.

PMID- 9927982
TI  - The Lichtenstein repair.
AB  - The description of the Lichtenstein tension-free mesh repair 12 years ago opened
      a new era in groin hernia repair. Without the risk for severe morbidity, it can
      be readily carried out on patients previously considered unsuitable for hernia
      repair. Fears of complications related to mesh implantation have proved to be
      without foundation. As a local anesthetic outpatient procedure without the need
      for complex and expensive instrumentation, combined with the ability of patients
      to return to work in a short time, overall costs can be kept to a minimum without
      in any way compromising the safety or the long-term success of the procedure.

PMID- 9927983
TI  - Laparoscopic repair and groin hernia surgery.
AB  - Over the past 15 years, laparoscopic herniorrhaphy has made the transition from
      an experimental to a proven procedure. With increasing laparoscopic skills in the
      surgical community, many surgeons are now faced with the question of when to
      recommend laparoscopic herniorrhaphy to their patients. A surgeon's best hernia
      repair is the one with which they have had the greatest experience. This results
      in the lowest recurrence and complication rate in his or her hands. Certainly,
      simple, unilateral hernias and bilateral hernias can be repaired with either
      anterior or laparoscopic techniques. Many times, laparoscopic herniorrhaphy is
      too much surgery for a young patient with a unilateral hernia. In such a case,
      repair is best performed with the patient under local anesthesia. Also, young
      patients in whom it is advantageous to avoid mesh should not undergo laparoscopic
      herniorrhaphy. The authors prefer laparoscopic TEP herniorrhaphy in patients with
      recurrent hernias, bilateral hernias, and unilateral hernias with a suspected
      contralateral hernia. There is also a consensus that patients with multiple
      recurrent hernias in whom a preperitoneal repair is appropriate are best served
      with a laparoscopic repair. Surgeons without advanced laparoscopic skills or
      without the time to develop the skills necessary to perform laparoscopic
      herniorrhaphy should consider referring patients with recurrent hernias to
      surgeons with experience in TEP. TEP is preferable to TAPP because of its lower
      complication and recurrence rates and in the authors' hands is the "best repair."
      TAPP should be reserved for patients with prior lower abdominal wall incisions
      that make the dissection of the peritoneum from the underside of the incision
      impossible. Patients who cannot tolerate general anesthesia or who have had
      extensive lower abdominal surgery should not undergo laparoscopic herniorrhaphy.
      Complication and recurrence rates, although initially higher than traditional
      repairs, have now fallen to equal or lower levels at centers experienced in
      laparoscopic techniques. Prospective randomized trials prove that when patients
      are selected properly and surgeons are adequately trained and proctored,
      laparoscopic herniorrhaphy can be performed with acceptably low incidences of
      recurrence and complications.

PMID- 9927984
TI  - Inguinal hernia repair. The Nyhus posterior preperitoneal operation.
AB  - The posterior preperitoneal approach for prosthetic hernioplasty is a safe and
      sound procedure for the repair of adult groin hernias. The authors' results, 0
      mortality, 2.1% minor morbidity, and 2.1% overall recurrence rate (1.26% for mesh
      hernioplasty), compare favorably with results in contemporary literature. This
      operation can be performed as an outpatient procedure or 1-night stay surgery.
      Pain is significantly less than with the traditional anterior Cooper's ligament
      repair, and rapid return to ordinary daily activities is possible. The authors
      favor the use of mesh prostheses in most cases of adult Nyhus types 2, 3 (not
      necessary in crural hernias), and 4 hernias. The authors recognize the value of
      two new approaches to hernia repair, that is, the laparoscopic extraperitoneal
      method and the tension-free mesh-plug hernioplasty, which share many of the
      anatomophysiologic principles with the posterior preperitoneal mesh repair.

PMID- 9927985
TI  - Giant prosthetic reinforcement of the visceral sac. The Stoppa groin hernia
      repair.
AB  - GPRVS is a properitoneal hernioplasty with a prosthesis composed of the polyester
      Dacron. The repair is anatomic, sutureless, tension-free, and the absolute weapon
      to eliminate all types of groin hernias. No other technique produces better
      results for the repair of recurrent and re-recurrent groin hernias. It also is a
      joy to perform.

PMID- 9927986
TI  - Complications of groin hernia surgery.
AB  - Groin hernias represent one of the most common procedures performed in general
      hospitals. The rapid changes that have been witnessed in prosthetic materials,
      open-approach surgeries, and laparoscopic techniques have made hernia surgery a
      most interesting field of endeavor that demands renewed discipline and
      dedication.

PMID- 9927987
TI  - Pathophysiology, prevention, and management of prosthetic infections in hernia
      surgery.
AB  - Because hernias are repaired increasingly with mesh and plugs, surgeons
      performing these operations should make an extended effort to prevent infection,
      and, when infections occur, to treat them expeditiously. This article discusses
      bacterial binding, infection reduction, the patient-doctor relationship during
      the care of an infected wound, and other related topics.

PMID- 9927988
TI  - Classification systems and groin hernias.
AB  - The once simple division of groin hernias into indirect and direct inguinal and
      femoral components is no longer adequate to reflect a more sophisticated
      understanding of the pathophysiology and management of these lesions. Similarly,
      the availability of a concise, easy-to-use, logical, and recognizable
      classification scheme would facilitate a better understanding of modern repair
      techniques and confirmation of operative results.

PMID- 9927989
TI  - Audit of patient outcomes after herniorrhaphy.
AB  - The efficacy of a surgical procedure is a measure of outcome when performed by
      specialists. The monotonous excellence of countless cohort studies bears witness
      to the efficacy of numerous techniques of herniorrhaphy. Effectiveness, however,
      is of far greater relevance to health care commissioners than efficacy. Audit is
      an instrument of effectiveness and can be further developed to study cost
      effectiveness where outcomes do not differ greatly.

PMID- 9927990
TI  - Hernia registers and specialization.
AB  - Registration of hernia surgery is useful in the demonstration of outcome quality
      provided reoperation is linked to the primary procedure. Prerequisites for a
      hernia register are discussed based on Swedish experience. Evidence indicates
      that register participation reduces reoperation rate and increases
      costeffectiveness. Monitoring of outcome quality is important for both
      specialized and nonspecialized hernia surgeons. Registers of the type discussed
      may assist general surgeons in their efforts to achieve levels defined by
      experts.

PMID- 9927992
TI  - Cis-regulatory elements controlling basal and inducible VIP gene transcription.
AB  - The cis-acting elements of the VIP gene important for basal and stimulated
      transcription have been studied by transfection of VIP-reporter gene constructs
      into distinct human neuroblastoma cell lines in which VIP transcription is
      constitutively high, or can be induced to high levels by protein kinase
      stimulation. The 5.2 kb flanking sequence of the VIP gene conferring correct
      basal and inducible VIP gene expression onto a reporter gene in these cell lines
      was systematically deleted to define its minimal components. A 425-bp fragment (
      4656 to -4231) fused to the proximal 1.55 kb of the VIP promoter-enhancer was
      absolutely required for cell-specific basal and inducible transcription. Four
      additional components of the VIP gene were required for full cell-specific
      expression driven by the 425 bp TSE (region A). Sequences from -1.55 to -1.37
      (region B), -1.37 to -1.28 (region C), -1.28 to -.094 (region D), and the CRE
      containing proximal 94 bp (region E) were deleted in various combinations to
      demonstrate the specific contributions of each region to correct basal and
      inducible VIP gene expression. Deletion of region B, or mutational inactivation
      of the CRE in region E, resulted in constructs with low transcriptional activity
      in VIP-expressing cell lines. Deletion of regions B and C together resulted in a
      gain of transcriptional activity, but without cell specificity. All five domains
      of the VIP gene were also required for cell-specific induction of VIP gene
      expression with phorbol ester. Gelshift analysis of putative regulatory sequences
      in regions A-D suggests that both ubiquitous and neuron-specific trans-acting
      proteins participate in VIP gene regulation.

PMID- 9927991
TI  - Signaling by the cytokine receptor superfamily.
AB  - A variety of cytokines that regulate functions of multiple lineages share the
      utilization of receptors that are structurally and functionally related and are
      referred to as the cytokine receptor superfamily. These receptors associate with
      one or more of the four mammalian Janus kinases (Jaks) and ligand-induced
      receptor aggregation results in their activation. Critical roles for Jak3 and
      Jak2 are demonstrated by the phenotypes of mice that lack each gene. Among the
      substrates of the Jaks are one or more of the seven members of the signal
      transducers and activators of transcription (Stats). Each Stat family member
      plays a critical role in the biological functions of specific cytokines as
      demonstrated by the phenotype of mice lacking one or more of these genes.

PMID- 9927993
TI  - p22/PACAP response gene 1 (PRG1): a putative target gene for the tumor suppressor
      p53.
AB  - In this study we describe a novel putative p53-responsive gene, designated
      p22/PACAP response gene 1 (PRG1), recently identified as a proliferation
      associated early-response gene in rats. By means of electrophoretic mobility
      shift assay and CAT-reporter gene assay, we could demonstrate that the p53
      binding site residing in the promoter of p22/PRG1 is functional in vitro.
      Furthermore, in clone 6 cells expression of p22/PRG1 is induced in parallel to
      p21/Waf1 under conditions permitting mutant p53 to adopt wild-type configuration.
      An increase of p22/PRG1 transcription was also observed in gamma-irradiated rat
      splenocytes, which undergo p53-dependent apoptosis. Our findings demonstrate that
      p22/PRG1 fulfills all essential criteria as a p53 target gene and might be
      implicated in p53-dependent apoptosis.

PMID- 9927994
TI  - Solution structure comparison of the VIP/PACAP family of peptides by NMR
      spectroscopy.
AB  - The current status of structural studies of the VIP/PACAP family of peptides in
      solution by NMR spectroscopy is briefly reviewed. The structural elucidation
      methodology is described with examples from recent work and finally general
      structural conclusions are drawn from data from the now extensive literature.

PMID- 9927995
TI  - Cloning and functional characterization of PACAP-specific receptors in zebrafish.
AB  - Two PACAP receptors were isolated from total zebrafish cDNA library prepared from
      6-day old fish by a homology-based cloning strategy. The two zebrafish PACAP
      receptors have the same topology as the one found in other members of this class
      of seven membrane-spanning G-protein-coupled receptors. Each of the two zebrafish
      PACAP receptors shares about 70% sequence identity at the amino acid level with
      the human PACAP-type 1 receptor, and about 50% amino acid identity with PACAP/VIP
      R-1 and PACAP/VIP R-2 receptors. One of these zebrafish receptors contains the
      hop2 configuration found in the human and rat PACAP-type 1 receptors. On the
      basis of these structural characteristics the zebrafish PACAP receptors were
      classified as PACAP-type 1 and PACAP-type 2 receptors. In competitive binding
      experiments zebrafish PACAP-type 1 and PACAP-type 2 receptors showed similar
      binding specificity for zebrafish and human PACAP-38 and PACAP-27. Furthermore,
      the specificity of PACAP-type 1 and PACAP-type 2 receptors for zebrafish and
      human PACAPs is about 1,000-fold higher than for human VIP. These results
      demonstrate that zebrafish PACAP-type 1 receptor is a structural and
      pharmacological homolog of the mammalian PACAP-type 1 receptor. Additional
      pharmacological characterization is needed in order to classify the zebrafish
      PACAP-type 2 receptor.

PMID- 9927996
TI  - Induction of type I PACAP receptor expression by the new zinc finger protein Zac1
      and p53.
AB  - We reported recently the cloning of the type I PACAP receptor by a functional
      expression cloning technique. Unexpectedly, we observed additional PACAP-positive
      pools that turned out to encode the wild-type form of the tumor suppressor gene
      p53 and the novel zinc finger protein Zac1, which regulates apoptosis and cell
      cycle arrest. Both Zac1 and p53 caused, under transient or stably regulated
      expression, induction of the type I PACAP receptor by transcriptional mechanisms.
      Transactivation of the type I PACAP receptor gene by Zac1 and p53 points to a
      subtle balance between death promoting and protective mechanisms. The control of
      these processes is central to various physiological conditions ranging from
      development to senescence, whereas dysregulation may lead to overt pathological
      outcomes, notably cancer, immune deficiency syndromes, and neurodegenerative
      disorders.

PMID- 9927997
TI  - Cloning and functional characterization of the human VIP1/PACAP receptor
      promoter.
AB  - The 5'-flanking region (1.5 kb) of the gene coding for the human VIP1/PACAP
      receptor was isolated, sequenced, and characterized. Transient expression of
      constructs containing sequentially deleted 5'-flanking sequences of the
      VIP1/PACAP receptor fused to a luciferase reporter gene showed that this sequence
      was active as a promoter in the intestinal cancer cell line, HT-29, expressing
      endogenous VIP1/PACAP receptor. The shortest DNA fragment with significant
      promoter activity encompassed the region from -205 to +76 bp. Deletion of a CCAAT
      box sequence in the construction corresponding to -173 to +76 bp dramatically
      reduced the promoter activity. The promoter -205 to +76 bp has a housekeeping
      gene structure without TATA-box. It contains GC-rich regions characterized by
      potential Sp1 and AP2 sites and some potential regulatory elements, such as CRE
      and ATF, and a CCAAT-box sequence (-182 to -178) crucial for gene transcription.

PMID- 9927998
TI  - Desensitization of the human vasoactive intestinal peptide receptor (hVIP2/PACAP
      R): evidence for agonist-induced receptor phosphorylation and internalization.
AB  - To investigate the role of phosphorylation and internalization in the
      desensitization of the hVIP2/PACAP receptor, we expressed a C-terminal epitope
      tagged (hemagglutinin; YPYDVPDYASL) receptor in COS7 and HEK293 cell lines.
      Radiolabeling experiments demonstrated that exposure to agonist induced receptor
      phosphorylation significantly above basal levels. This receptor phosphorylation
      was greater than that induced by receptor-independent activation of PKA with
      forskolin and that induced by co-application of forskolin and agonist. This
      suggests that receptor occupancy promotes phosphorylation and also that receptor
      phosphorylation may involve a specific G protein-coupled receptor kinase in
      addition to PKA. Immunocytochemical analysis showed that the receptor was
      internalized in response to agonist to a single site of accumulation within the
      cell and this was dependent on temperature, agonist concentration, and time.
      Further studies will focus on identifying phosphorylation sites and endocytic
      signals within the hVIP2/PACAP R.

PMID- 9927999
TI  - Rat aortic smooth-muscle cell proliferation is bidirectionally regulated in a
      cell cycle-dependent manner via PACAP/VIP type 2 receptor.
AB  - In the cardiovascular system, vasoactive intestinal polypeptide (VIP) and
      pituitary adenylate cyclase activating polypeptide (PACAP) have been well
      characterized as potent vasodepressors or vasodilators. However, their
      pathophysiological implication in proliferation of vascular smooth muscle cells
      has not yet been elucidated. In the present study, we have first identified
      PACAP/VIP type 2 receptor as a dominant type in rat vascular smooth muscle cell
      (VSMC) by RT-PCR. PACAP and VIP increased cyclic AMP accumulation with similar
      potency. In 24-h [3H]thymidine incorporation assay, PACAP or VIP exhibited a
      suppressive effect on the DNA synthesis of rat VSMC stimulated by serum when
      added at the late G1 phase. In contrast, when added at G0/G1 phase of the cell
      cycle, PACAP or VIP enhanced the serum-induced DNA synthesis. In 24-h incubation,
      PACAP alone has little mitogenic activity. However, when incubated up to 48 h,
      PACAP stimulated significantly the DNA synthesis and the cell proliferation of
      rat VSMC. These results suggest that PACAP and VIP regulate the proliferation of
      rat VSMC by enhancing or suppressing in a cell cycle-dependent manner and induce
      delayed mitogenesis and cell proliferation.

PMID- 9928000
TI  - Identification of binding domains of pituitary adenylate cyclase activating
      polypeptide (PACAP) for its type 1 receptor by photoaffinity labeling.
AB  - Structure-function studies and photoaffinity labeling experiments were performed
      to identify residues and domains of PACAP involved in the interaction with PACAP
      receptors. For this purpose, a series of photoreactive analogues of PACAP(1-27)
      containing a photoreactive benzophenone (BP) residue in different peptide
      structural domains were utilized to analyze the interaction of PACAP(1-27) with
      pig PACAP type 1 receptors. Five PACAP derivatives were created with a
      photoreactive amino acid in the following peptide domains: either the disordered
      N-terminal or the helical C-terminal domain or a short loop region within the C
      terminal helical domain of the peptide. Their receptor binding properties and
      efficiencies were tested on pig brain PACAP receptors. The results indicate the
      importance of the helical C-terminal domain of PACAP(1-27) for receptor binding
      affinity. Monoiodination of the photoreactive analogues did not change their
      binding affinities. Experiments with pig brain membranes demonstrated that the
      125I-labeled photoreactive analogues specifically label a protein band of M(r)
      66,000. The efficiency of photoreactive labeling differed for the various
      analogues. These findings suggest that Tyr22 and Lys15 in PACAP (1-27) are
      located in or close to the hormone binding site of the PACAP type 1 receptor. The
      results provide evidence that the alpha-helical C-terminal region of PACAP is
      directly involved in receptor binding.

PMID- 9928001
TI  - The neurotrophic activity of PACAP on rat cerebellar granule cells is associated
      with activation of the protein kinase A pathway and c-fos gene expression.
AB  - In vitro studies have shown that PACAP promotes cell survival and neurite
      outgrowth in immature cerebellar granule cells. In the present study, we have
      examined the transduction pathways involved in the neurotrophic activity of
      PACAP. Incubation of cultured granule cells with graded concentrations of PACAP
      produced a dose-dependent increase in c-fos mRNA level. The effects of PACAP on c
      fos gene expression and granule cell survival were both mimicked by dbcAMP but
      not by PMA. The maximum effect of PACAP on c-fos gene expression was observed
      after 1 h of treatment. Similar effects of the peptide on granule cell survival
      were observed whether the cells were continuously incubated with PACAP for 48 h
      or only exposed to PACAP during 1 h. The PKA inhibitor H89 significantly reduced
      the effect of PACAP on c-fos mRNA level, whereas the specific PKC inhibitor
      chelerytrine had no effect. These data indicate that the action of PACAP on
      cerebellar granule cell survival and c-fos gene expression are both mediated
      through the adenylyl cyclase/PKA pathway.

PMID- 9928002
TI  - PACAP-38 protects cerebellar granule cells from apoptosis.
AB  - Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and -38) are
      neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon
      family. PACAP receptors are expressed in different brain regions including the
      cerebellum. We used primary culture of rat cerebellar granule neurons to study
      the effect of PACAP-38 on apoptosis induced by potassium deprivation. We
      demonstrated that serum and potassium withdrawal induces a mixture of apoptosis
      and necrosis rather than apoptosis only. We showed that PACAP-38 increased
      survival of cerebellar neurons in a dose-dependent manner by specifically
      decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38
      induced activation of the extracellular signal-regulated kinase (ERK)-type of MAP
      kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase
      kinase), completely abolished the anti-apoptotic effect of PACAP-38, suggesting
      that MAP kinase pathway activation is necessary for PACAP-38 effect.

PMID- 9928003
TI  - PACAP protects hippocampal neurons against apoptosis: involvement of JNK/SAPK
      signaling pathway.
AB  - We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1
      region of the rat hippocampus was prevented by either intracerebroventricular or
      intravenous infusion of pituitary adenylate cyclase-activating polypeptide
      (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect
      of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of
      members of the mitogen-activated protein (MAP) kinase family, including
      extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)/stress
      activated protein kinase (SAPK), and p38 were increased in the hippocampus. The
      ischemic stress had a potent influence on the MAP kinase family, especially on
      JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress.
      Secretion of interleukin-6 (IL-6) into the cerebrospinal fluid was intensely
      stimulated after PACAP infusion. IL-6 inhibited the activation of JNK/SAPK, while
      it activated ERK. These observations suggest that PACAP and IL-6 act to inhibit
      the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis.

PMID- 9928004
TI  - Stimulatory transducing systems in pancreatic islet cells.
AB  - We have determined the cellular distribution of different alpha subtypes of G
      proteins and adenylyl cyclase (AC) isoforms in endocrine, exocrine, and
      established pancreatic cell lines. VIP, PACAP, and tGLP-1 receptor proteins are
      expressed to varying extents in A and B cells, whereas the expression of G alpha
      subunits is cell specific. Thus, G(olf) alpha is detected in normal rodent B
      cells and immortalized pancreatic B cell lines, whereas Gs alpha is more
      ubiquitously expressed. The cellular density of AC isoforms labeling (I, II, III,
      IV, V/VI) is also islet cell-specific and their distribution is age- and species
      dependent. The identification of numerous signaling molecule subtypes, together
      with the discovery of their specific subcellular distribution, will help the
      functional characterization of their intraregulatory pathways, leading to the
      extrusion of insulin or glucagon secretory granules, and those leading to
      differentiation and apoptosis of islet cells.

PMID- 9928005
TI  - Miniglucagon: a local regulator of islet physiology.
AB  - Miniglucagon, or glucagon-[19-29], is partially processed from glucagon in its
      target tissues where it modulates the glucagon action. In the islets of
      Langerhans, the glucagon-producing A cells contain miniglucagon at a significant
      level (2-5% of the glucagon content). We studied a possible control of insulin
      release by miniglucagon using as a model the MIN6 cell line. Miniglucagon, in the
      10(-14) to 10(-9) M range, inhibited insulin release induced by glucose,
      glucagon, tGLP-1, or glibenclamide by 85-100% with an IC50 close to 1 pM. While
      no change in the cyclic AMP content was noted, Ca2+ influx was reduced in
      parallel with the inhibition of insulin release. Use of pharmacological
      modulators of L-type voltage-sensitive Ca2+ channels and bacterial toxins
      indicates that miniglucagon blocks insulin release by closing this type of
      channel via a pertussis toxin-sensitive G protein. Miniglucagon is a novel,
      possibly physiologically relevant, local regulator of islet function.

PMID- 9928006
TI  - Pituitary adenylate cyclase activating polypeptide induces degranulation of rat
      peritoneal mast cells via high-affinity PACAP receptor-independent activation of
      G proteins.
AB  - In this study, the secretory effects of PACAP and PACAP analogues on
      [3H]serotonin-loaded purified rat peritoneal mast cells (RPMCs) were
      investigated. PACAP(1-27) and PACAP(6-27) stimulated [3H]serotonin release with
      low potency (ED50: 2 x 10(-6) M) but high efficacy. The N-terminally truncated
      PACAP form, PACAP(6-27), stimulated tracer release with an ED50 of 0.2 x 10(-6)
      M, indicating a high-affinity PACAP receptor-independent mechanism of action. The
      secretory response to PACAP(1-27) could be inhibited by 60-min preincubation with
      pertussis toxin (ptx), which inhibits G proteins. U73122, a cell-permeable
      phospholipase C inhibitor, dose-dependently inhibited the secretory effect of 5
      microM PACAP(1-27) with an IC50 value of 4 microM (N = 4; p < 0.006). We conclude
      that PACAP exerts a secretory effect in RPMCs by high-affinity PACAP receptor
      independent direct activation of one or more G proteins, which may then activate
      the PLC-dependent signal-transduction pathway.

PMID- 9928007
TI  - The pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1-R)
      is expressed on gastric ECL cells: evidence by immunocytochemistry and RT-PCR.
AB  - The current study was undertaken to determine the presence and distribution of
      PAC1-Rs within the gastric mucosa. Polyclonal antibodies to the carboxyl terminus
      of the rat PAC1-R were generated and shown to be specific against the PAC1-R
      expressed in NIH 3T3 cells. Western blot analysis using isolated (approximately
      85% pure) ECL cell membranes identified a 48 kD protein consistent with the
      calculated molecular mass of the cloned PAC1-R. RT/PCR performed using specific
      primers for the PAC1-R confirmed the presence of splice variants of the rat PAC1
      R, but not VPAC1-R or VPAC2-R. These data provide the first direct evidence for
      the existence of functional PACAP Type I receptors on ECL cells of the gastric
      mucosa and suggest a potential role for PACAP in the stimulation of gastric acid
      secretion and in the regulation of the growth of ECL cells.

PMID- 9928008
TI  - A critical view of the methods for characterization of the VIP/PACAP receptor
      subclasses.
AB  - The binding properties of the three cloned VIP/PACAP receptors and their coupling
      to G proteins and effectors can be studied in cells expressing each recombinant
      protein. The data obtained in these models must be critically evaluated: the
      expression of a high receptor density may reveal irrelevant receptors states and
      coupling to non-cognate G protein, and entail a marked amplification of the
      response as well as distortions in the selectivity profile of full and partial
      agonists. These models are, however, of great interest in the design of selective
      agonists and antagonists for each receptor subtype. The availability of selective
      ligands will facilitate the identification of the receptor subtype responsible
      for PACAP and VIP actions in cells and tissues.

PMID- 9928009
TI  - Mechanisms of pituitary adenylate cyclase activating polypeptide (PACAP)-induced
      depolarization of sympathetic superior cervical ganglion (SCG) neurons.
AB  - Our understanding of PACAP expression and regulation of sympathetic neuronal
      function has been augmented considerably over the last few years. Among the three
      major VIP/PACAP receptor subtypes, the SCG appears to express preferentially one
      particular variant of the PACAP-selective PACAP1 receptor coupled to multiple
      intracellular signaling cascades. The in situ histochemical hybridization and
      immunocytochemical studies of PACAP1 receptor mRNA and protein are in good
      agreement; nearly all of the SCG neurons express the PACAP-selective receptor,
      suggesting that most of the sympathetic neurons are under PACAP neuromodulation.
      In accord with that possibility, several independent studies have now
      demonstrated PACAP peptide expression in the IML sympathetic preganglionic
      neurons and fibers, including those projecting to the SCG, further emphasizing
      the significance of PACAP peptides as a preganglionic noncholinergic mediator of
      sympathetic function. Given the high potency of PACAP on any of a number of
      cellular responses, the functional relevance of PACAP peptides on SCG neurons is
      considerable. We have previously demonstrated the potency and efficacy of both
      PACAP27 and PACAP38 on sympathetic neuron neurotransmitter/neuropeptide
      production and secretion; the ability of these peptides to stimulate neuronal
      second messenger activation was also in the nanomolar range. These results are
      congruous with our current electrophysiological studies, which were driven to
      further define the dynamic sympathetic responses to PACAP. In line with the
      morphological studies, for example, more than 90% of the sympathetic neurons
      responded to PACAP. In agreement with previous neuropharmacological data, the
      PACAP-induced depolarizations were elicited at physiologically relevant peptide
      concentrations at high affinity PACAP-selective receptors. The effects were
      direct and the alterations in postganglionic neuronal membrane properties
      appeared to be mediated by several ionic mechanisms. If these studies were
      analogous to pieces in a puzzle to understand the effects of PACAP in sympathetic
      development and function, the picture of late has been more completely assembled.
      But several important challenges still remain. What are the signal transduction
      mechanisms that mediate the PACAP-induced changes in sympathetic membrane
      properties? How do the resulting alterations impact the acute and more long-term
      responses of sympathetic neurons? Does the coupling of PACAP1 receptors to
      intracellular signaling pathways differ during development, resulting in a
      transition from the neurotrophic properties of PACAP in neuroblasts to
      neuromodulatory roles of the peptides in postmitotic neurons? By looking at these
      issues in one distinct neuronal system, we enlarge our understanding and
      appreciation of peptides, and PACAP in particular, in the molecular and cellular
      events guiding neuronal development, function, and plasticity.

PMID- 9928010
TI  - Sympathetic neurons of the chick embryo are rescued by PACAP from apoptotic
      death.

PMID- 9928011
TI  - Differential display PCR reveals induction of immediate early genes by vasoactive
      intestinal peptide in PC12 cells.
AB  - In order to identify genes regulated by vasoactive intestinal peptide, we
      performed differential display PCR as originally described by Liang and Pardee.
      Messenger RNA of PC12 cells treated with vasoactive intestinal peptide or nerve
      growth factor for one hour was reverse transcribed and amplified using different
      sets of oligo-dT and random primers. Radioactively labeled PCR products were
      displayed on polyacrylamide gels and candidate cDNAs extracted from the gel, re
      amplified by PCR, cloned, and sequenced. Differential expression was verified by
      RT-PCR applying sets of specific primers obtained from the sequence. The
      specificity of the PCR product was confirmed by Southern blotting using a
      radioactively labeled internal primer and semi-quantitative densitometric
      analysis. This rapid and sensitive protocol led to the isolation of two immediate
      early genes, pip92 and PC4, known to be increased on mRNA level by nerve growth
      factor in PC 12 cells.

PMID- 9928012
TI  - Developmental regulation of pituitary adenylate cyclase activating polypeptide
      (PACAP) and its receptor 1 in rat brain: function of PACAP as a neurotrophic
      factor.
AB  - To function as a trophic factor PACAP and PACAP-R must be expressed in the
      nervous system during early development. We report here on the distribution of
      PACAP mRNA in the developing nervous system of the rat and compare its expression
      with that of PACAP-R. We discuss primary neuron culture experiments that study
      the neurotrophic activity of PACAP. Experimental results that indicate the
      presence of PACAP and its receptor in the developing nervous system, together
      with the observed neuropeptide activity on various populations of neurons,
      support the view that PACAP exhibits important neurotrophic activities comparable
      to those of the classical neurotrophic factors.

PMID- 9928013
TI  - Pituitary adenylate cyclase activating peptide (PACAP) in the retinohypothalamic
      tract: a daytime regulator of the biological clock.
AB  - The retinohypothalamic tract (RHT) relays photic information from the eyes to the
      brain biological clock in the suprachiasmatic nucleus (SCN). Activation of this
      pathway by light plays a role in adjusting circadian timing to light exposure at
      night. Here we report a new signaling pathway by which the RHT regulates
      circadian timing in the daytime as well. Using dual-immunocytochemistry for PACAP
      and the in vivo tracer Cholera toxin subunit B (ChB), intense PACAP
      immunoreactivity (PACAP-IR) was observed in retinal afferents at the rat SCN as
      well as in the intergeniculate leaflet (IGL) of the thalamus. This PACAP-IR was
      nearly lost upon bilateral eye enucleation. PACAP afferents originated from
      ganglion cells distributed throughout the retina. The phase of circadian rhythm
      measured as SCN neuronal activity in vitro was significantly advanced by
      application of PACAP-38 during the subjective day, but not at night. The effect
      is channelled to the clock via a PACAP 1 receptor-cAMP signaling mechanism. Thus,
      in addition to its role in nocturnal regulation by glutamatergic
      neurotransmission, the RHT can adjust the biological clock by a PACAP-cAMP
      dependent mechanism during the daytime.

PMID- 9928014
TI  - VIP neurotrophism in the central nervous system: multiple effectors and
      identification of a femtomolar-acting neuroprotective peptide.
AB  - Vasoactive intestinal peptide has neurotrophic and growth-regulating properties.
      As in the case of many neurotrophic molecules, VIP also has neuroprotective
      properties, including the prevention of cell death associated with excitotoxicity
      (NMDA), beta-amyloid peptide, and gp120, the neurotoxic envelope protein from the
      human immunodeficiency virus. The neurotrophic and neuroprotective properties are
      mediated in part through the action of glial-derived substances released by VIP.
      These substance include cytokines, protease nexin I, and ADNF, a novel
      neuroprotective protein with structural similarities to heat-shock protein 60.
      Antiserum against ADNF produced neuronal cell death and an increase in apoptotic
      neurons in cell culture. A 14 amino acid peptide (ADNF-14) derived from ADNF has
      been discovered that mimics the survival-promoting action of the parent protein.
      These studies support the conclusion that VIP, PACAP, and associated molecules
      are both important regulators of neurodevelopment and strong candidates for
      therapeutic development for the treatment of neurodegenerative disease.

PMID- 9928015
TI  - VIP and PACAP in the CNS: regulators of glial energy metabolism and modulators of
      glutamatergic signaling.
AB  - VIP neurons are a homogeneous population of intracortical bipolar cells. They
      receive excitatory synapses from afferent circuits to the cortex and exert
      effects on neurons, astrocytes, and capillaries. Effects on the two latter cell
      types imply that VIP neurons can translate incoming neuronal signals into local
      metabolic actions. Indeed, VIP tightly regulates glycogen metabolism in
      astrocytes. In this cell type VIP regulates the expression of a number of genes
      related to energy metabolism, such as glycogen synthase. These effects of VIP
      involve the transcription factor family C/EBP and result in the induction of at
      least seven new proteins by astrocytes. The actions of VIP on neurons appear to
      be of a modulatory nature: thus VIP enhances glutamate-mediated neurotransmission
      by potentiating the effects of glutamate on arachidonic acid formation and on the
      induction of c-fos and on BDNF expression. These effects indicate that VIP can
      actually increase the strength of glutamate-mediated neurotransmission.

PMID- 9928017
TI  - Autoantibody catalysis: no longer hostage to Occam's razor.
AB  - Autoantibody catalysis is now a well-established phenomenon, but the initial
      finding of autoantibody-catalyzed VIP cleavage was suspected to be an artefact by
      certain practitioners of designer antibody catalysis, mainly because of
      conceptual complexities not foreseen in our training about the immune system and
      about the mechanisms of biological catalysis. Confirmation that antibodies can
      acquire proteolytic activity by entirely natural means has emerged, ironically,
      in part from the field of designer catalytic antibodies. Recent studies have
      provided insight into the molecular strategies whereby antibodies can combine
      antigen binding with chemical catalysis, and the contributions of innate and
      adaptive immune mechanisms in the proteolytic activity. The history of this field
      illustrates the dangers of assuming that novel observations must fit into the
      simple confines of established theories. Scientific theories are changeable
      entities, dependent on empirical data and interpretations of the data, and their
      growth is better served by keeping an open mind.

PMID- 9928016
TI  - Glutamate toxicity in the lung and neuronal cells: prevention or attenuation by
      VIP and PACAP.
AB  - VIP, which has been demonstrated to reduce or prevent oxidant injury in the lungs
      and other organs, is shown here to protect against excitotoxic injury of the lung
      and excitotoxic death of cortical neuronal cells in primary culture. Glutamate
      killing of neuron-like PC-12 cells, attributable to oxidant stress rather that to
      excitotoxicity, is also reduced or prevented by VIP and by the closely related
      peptide PACAP. The exact mechanisms of this protection remain to be determined,
      but appear to include antioxidant and anti-apoptotic actions, and suppression of
      glutamate-induced upregulation of its own receptor. Both VIP and PACAP offer the
      promise of novel and nontoxic means of defending against NMDA and glutamate
      toxicity.

PMID- 9928018
TI  - Analogues of VIP, helodermin, and PACAP discriminate between rat and human VIP1
      and VIP2 receptors.
AB  - Vasoactive intestinal polypeptide (VIP) acts through interaction with two
      subclasses of seven transmembrane G protein-coupled receptors named VIP1 and VIP2
      receptors. These receptors have been cloned in different species, such as rat and
      human. Considering the different distribution of both receptor subclasses, there
      is considerable interest in the development of selective agonists and
      antagonists. The present study compares the binding properties of VIP, PACAP,
      GRF, secretin, and helodermin analogues on recombinant rat and human VIP1 and
      VIP2 receptors. On both rat and human receptors, secretin and GRF had a higher
      affinity for the VIP1 receptor subtypes. The amino-shortened VIP, and the carboxy
      terminal-shortened VIP and PACAP analogues also presented a higher affinity for
      the VIP1 receptor. PHI, PHV, helodermin, and helospectin were selective for the
      human VIP2 receptor subtypes. These results suggest that the helical structure of
      the carboxy terminal end is necessary for VIP2 recognition. The differences
      between species were the following: PHI, PHV, helodermin, and helospectin had a
      higher affinity for the rat VIP1 receptor than for the human VIP1 receptor. On
      both rat and human receptors, D-Ala4 VIP and D-Phe4 VIP had a high affinity for
      the VIP1 receptor and a low affinity for the VIP2 receptor. Thus, three domains
      of the ligand involved in VIP1/VIP2 receptor discrimination were identified: the
      amino acid residue in position 4 ([D-Ala4], [D-Phe4]VIP), in positions 8 and 9
      (the effects of helodermin and helospectin), and the carboxy terminal end (the
      effects of the shortened VIP and pituitary adenylate cyclase activating
      polypeptide analogues).

PMID- 9928019
TI  - Maxadilan is a specific agonist and its deleted peptide (M65) is a specific
      antagonist for PACAP type 1 receptor.
AB  - Maxadilan is a potent vasodilator peptide isolated from salivary glands extracts
      of the hematophagous sand fly. Recently, it was demonstrated that maxadilan binds
      to PACAP receptor type 1 in mammals, although maxadilan has no significant amino
      acid sequence homology with PACAP. In the present study, we demonstrated that
      maxadilan is a specific agonist of PACAP type 1 receptor (PACAP/VIP receptor 1;
      PVR1) as determined by the binding assay of [125I]PACAP27 and cAMP accumulation
      using CHO cells stably expressing PVR1, VIP1 receptor (PVR2), and VIP2 receptor
      (PVR3), and that the deleted peptide (#25-41) of maxadilan (termed as M65) is a
      specific antagonist of PVR1. In addition, maxadilan shares the binding sites for
      PACAP and stimulates cAMP in cultured rat cortical neurons. VIP stimulates cAMP
      accumulation probably through the binding to PVR1 since M65 blocks the VIP
      induced cAMP accumulation in cultured rat cortical neurons.

PMID- 9928020
TI  - Importance of conserved cysteines in the extracellular loops of human PACAP/VIP1
      receptor for ligand binding and stimulation of cAMP production.
AB  - The importance of two highly conserved cysteines in the human pituitary adenylate
      cyclase activating polypeptide (PACAP)/vasoactive intestinal peptide 1 (VIP1)
      receptor was examined. Using site-directed mutagenesis, each Cys residue was
      converted into Ala or Ser. The mutant and wildtype genes were transfected into
      HEK293 cells and tested for the ability to bind VIP and to activate cAMP
      production. Cys215Ala/Ser and Cys285Ala/Ser showed at least a tenfold decrease in
      binding affinity and receptor potency when compared to the wildtype. In
      contradiction to the wildtype receptor, both mutations were insensitive to
      dithiothreitol (DTT). The results indicate the existence of a disulfide bond
      between Cys215 and Cys285, which is important for stabilizing the receptor in the
      correct conformation for ligand binding and activation.

PMID- 9928021
TI  - Multiple actions of a hybrid PACAP antagonist: neuronal cell killing and
      inhibition of sperm motility.
AB  - Pituitary stimulating adenylate cyclase (PACAP) is a major regulatory peptide
      with two active molecular forms: PACAP-27 and PACAP-38. Both molecular forms
      promote neuronal survival and protect against neurotoxicity. Based on our
      previous hybrid peptide strategy in designing vasoactive intestinal peptide (VIP)
      antagonists, novel PACAP analogues were synthesized (neurotensin6-11 PACAP7-27
      and neurotensin6-11 PACAP7-38). In addition to the hybrid modification, the
      methionine in position 17 was replaced by norleucine (Nle). Treatment of rat
      cerebral cortical cultures for five days with the putative PACAP antagonists (1
      nM) resulted in a 35-45% reduction in neuronal cell counts as compared to
      controls. Neuronal cell death was already obtained at picomolar concentrations
      for the neurotensin6-11 PACAP7-27 antagonist with 70% death at 10(-8) M. Co
      administration of the PACAP hybrid analogue with picomolar amounts of PACAP-27 or
      Nle17-PACAP-27 attenuated the reduction in neuronal cell counts. While the
      protective effects of both analogues exhibited a peak at 1 pM concentrations, the
      Nle-containing agonist displayed a broader range of active concentrations (10(
      12)M-10(-9) M). The putative PACAP antagonist also inhibited sperm motility
      (golden hamster) in a dose-dependent manner as assessed in vitro. Complete
      inhibition was observed at 10 microM, suggesting a role for PACAP in sperm
      motility and sexual function. Thus, previous findings of a large number of PACAP
      and PACAP receptors in the nervous system and the reproductive system are now
      correlated with a function in neuronal survival and sperm motility. The structure
      activity studies suggest that the methionine in position 17 and the first six
      amino acids are important in the determination of PACAP activity, knowledge that
      may facilitate PACAP-based drug design.

PMID- 9928022
TI  - The PACAP ligand/receptor system regulates cerebral cortical neurogenesis.
AB  - The PACAP ligand/type I receptor system is expressed throughout the embryonic
      nervous system, suggesting roles in regulating neural patterning and
      neurogenesis. In the forebrain, precursors of the six-layered cerebral cortex
      cease dividing in a highly reproducible spatiotemporal sequence. The time of cell
      cycle exit in fact determines neuron laminar fate. Our studies indicate that
      PACAP signaling may elicit cortical precursor withdrawal from the cell cycle,
      antagonizing mitogenic stimulators. PACAP inhibited embryonic day 13.5 rat
      cortical precursor [3H]thymidine incorporation, decreasing the proportion of
      mitotic cells. PACAP promoted morphological and biochemical differentiation,
      indicating that PACAP-induced cell cycle withdrawal was accompanied by neuronal
      differentiation. In vivo, embryonic cortex contains PACAP. In culture, 85% of
      cells expressed PACAP while 64% exhibited receptor. Co-localization studies
      indicated that PACAP ligand and receptor were expressed by the mitotic precursors
      that divided in response to bFGF, suggesting that precursors integrate mitogenic
      and anti-mitogenic signals to determine the timing of cell cycle exit. The
      expression of PACAP ligand and receptor in precursors raised the possibility of
      autocrine function. Indeed, peptide antagonists increased proliferation,
      suggesting that the PACAP system is expressed to elicit cell cycle exit. During
      ontogeny, an inhibitory signal, such as PACAP, may be required to counter the
      stimulatory activity of mitogenic bFGF and IGFI whose expression during cortical
      neurogenesis is sustained. The dynamic interplay of positive and negative
      regulators would regulate the timing of cell cycle withdrawal, and thus neuronal
      phenotype and laminar position.

PMID- 9928023
TI  - VIP and breast cancer.
AB  - VIP1 receptors are present in breast cancer cells. VIP elevates the cAMP and
      stimulates nuclear oncogene expression in MCF-7 cells. VIPhybrid is a VIP
      receptor antagonist that inhibits breast cancer proliferation. A VIP analog has
      been developed for imaging breast tumors. Therefore VIP1 receptors may be
      utilized for the early detection and treatment of breast cancer.

PMID- 9928024
TI  - Coordinated role of vasoactive intestinal peptide and nitric oxide in
      cardioprotection.
AB  - The present study sought to examine the interrelationship between nitric oxide
      (NO) and vasoactive intestinal peptide (VIP) in myocardial protection. Isolated
      rat hearts were perfused for 15 min with buffer only (Group I); 0.3 mM VIP (Group
      II); 3 mM L-arginine (a precursor of NO) (Group III); VIP and aminoguanidine
      (iNOS blocker) (Group IV); or L-arginine plus VIP 10-28 (VIP inhibitor) (Group
      V). Each heart was then made globally ischemic for 30 min followed by 2 h
      reperfusion. Both VIP and NO were found to provide cardioprotection during
      ischemia and reperfusion. However, the beneficial effects of VIP and NO were
      reduced by inhibition of NO and VIP, respectively, suggesting that
      cardioprotection by VIP is modulated by NO and vice versa. The results of this
      study suggested a coordinated regulation by cardioprotection by NO and VIP.

PMID- 9928025
TI  - The protective effect of vasoactive intestinal peptide (VIP) on stress-induced
      gastric ulceration in rats.
AB  - The pathogenesis of cold-restraint stress ulcer involves various factors and is
      not completely understood. Mast cell degranulation, increased gastric muscular
      contractility, diminished mucosal blood flow, release of several biogenic amines,
      activated polymorphonuclear leukocytes, and lipid peroxidation which results from
      toxic oxygen molecules were suggested to be related to the production of gastric
      damage by cold-restraint stress. Recent evidence strongly indicates that VIP has
      a modulatory effect on tissue injury. Sprague-Dawley rats were used in two series
      of experiments. One set of rats was exposed to cold-restraint stress with some of
      the rats pretreated with VIP. The second set of rats was exposed to cold
      restraint stress and then was administered VIP for different durations. Cold
      restraint stress induced gastric lesions and mast cell degranulation and also
      increased lipid peroxidation in gastric tissue. VIP prevented stress-induced
      ulcers and mast cell degranulation and protected gastric tissue from lipid
      peroxidation. When VIP was used after induction of stress ulcer it was
      therapeutically beneficial. Thanks to its antioxidant and anti-inflammatory
      activity, VIP can be valuable in the prevention of gastric mucosal damage induced
      by cold-restraint stress.

PMID- 9928026
TI  - Is there appetite after GLP-1 and PACAP?
AB  - Anitobesity drugs must increase the sensitivity of the hypothalamic satiety
      center towards leptin and antagonize the synthesis and action of NPY. The array
      of pharmacologic tools available is vast and presently ineffective. Among peptide
      analogs considered for evaluation [NPY-5 antagonists and CCK-A, bombesin, amylin
      and melanocyte-stimulating hormone-4 (or melanin-concentrating hormone?)
      agonists], is there a place for GLP-1 and PACAP? GLP-1 receptors present in ARC,
      PVN, VMN, and SON are the target for both central and blood-borne GLP-1 in those
      hypothalamic neurons endowed with GLUT-2 and glucokinase. GLP-1, hypersecreted by
      L-cells after a meal, is a potent insulinotropic agent and, together with
      glucose, reduces food intake and induces c-fos in the ARC. PACAP is present in
      the ARC, PVN, and SCH, and its hypothalamic type I receptor elevates cAMP and
      inositol triphosphate in the PVN, where it may perhaps antagonize NPY-induced
      food intake and hyperinsulinemia. However, irrelevant neuroendocrine, autonomic,
      and circadian functions are also activated by this peptide, making it a less than
      ideal base on which to build an obesity treatment.

PMID- 9928027
TI  - On the treatment of diabetes mellitus with glucagon-like peptide-1.
AB  - As a therapeutic principle, the insulinotropic peptide, GLP-1, of the secretin
      glucagon family of peptides, has turned out to possess some remarkably attractive
      properties, including the capability of normalizing blood glucose concentrations
      in patients with non-insulin-dependent diabetes mellitus and promoting satiety
      and reducing food intake in healthy volunteers. Because of rapid and extensive
      metabolization, the peptide is not immediately clinically applicable and, as a
      therapeutic principle, GLP-1 is still in its infancy. Some possible avenues for
      circumventing these difficulties are the development of DPP-IV-resistant analogs,
      the inhibition of DPP-IV, enhancement of GLP-1 secretion, GLP delivery systems
      using continuous subcutaneous infusion or buccal tablets, GLP-1 absorption, and
      orally active, stable analogs. It seems likely that one or more of these
      approaches could result in a clinically useful development program.

PMID- 9928028
TI  - Binding sites for VIP in the reorganizing mucosa of the irradiated bowel.
AB  - Rats were given radiotherapy (total dose 30 Gy) over the abdomen. Seven days
      later specimens of the duodenum were prepared for in vitro receptor
      autoradiography using the radioligand [125I]VIP. The autoradiograms were
      quantitatively analyzed using a computer system. Histological examination
      revealed that a very marked reorganization of the mucosa had occurred in response
      to irradiation. Using receptor autoradiography, we found [125I]VIP-specific
      binding sites in the reorganizing mucosa, except where denudation had occurred.
      Such binding sites also occurred in the smooth muscle layer of the duodenal wall.
      The observations suggest that VIP has profound effects in radiation-induced
      enteropathy.

PMID- 9928029
TI  - Main sensory neuropeptides, but not VIP and NPY, are involved in bone remodeling
      during orthodontic tooth movement in the rat.
AB  - During orthodontic tooth movement (OTM) a remodeling of the periodontal ligament
      (PDL) and the alveolar bone occurs. We have recently observed that the expression
      of CGRP and substance P (SP) increases in the PDL and dental pulp in response to
      buccally directed OTM of the upper first molar in the rat. We have now examined
      whether there is also an involvement of VIP and NPY in this type of OTM. A
      sectional arch wire cemented to the upper incisors exerted an orthodontic force,
      mediated by a coil on the lingual side of the tooth, for 24 hours. It was
      observed that the blood vessels in the periodontal ligament were supplied with
      VIP- and NPY-immunoreactive (IR) nerve fibers, whereas VIP-IR nerve fibers in
      contrast to NPY-IR fibers were only occasionally observed in the dental pulp. No
      significant changes were observed in response to OTM. The observations suggest
      that VIP and NPY, in contrast to the main sensory neuropeptides CGRP and SP, are
      not involved in the tissue processes that occur in the remodeling of PDL and
      alveolar bone during orthodontic tooth movement.

PMID- 9928030
TI  - PACAP27 and other neuropeptides in the inferior mesenteric ganglion.
AB  - The presence and location of PACAP27-like immunoreactivity (PACAP27-LI) in the
      colon-inferior mesenteric ganglion (IMG) reflex pathway and the effect of
      exogenously administered PACAP27 on the excitability of IMG are reported. The
      results provide morphological and electrophysiological support for the hypothesis
      that PACAP modulates reflex activity between the large intestine and IMG. The
      intense excitatory effect would be expected to increase the rate of action
      potential discharge in IMG neurons, increasing sympathetic drive to the colon
      thereby decreasing of colonic activity.

PMID- 9928031
TI  - Induction of multiple pituitary adenylate cyclase activating polypeptide (PACAP)
      transcripts through alternative cleavage and polyadenylation of proPACAP
      precursor mRNA.
AB  - Many regulated events guide neuropeptide biosynthesis, processing, and secretion.
      For PACAP peptides, these events have not been well examined. In our studies of
      PACAP expression in sympathetic neurons, we discovered that neuronal
      depolarization not only increased the levels of the 2.2 kb form of proPACAP mRNA
      identified in neuronal tissues, but also induced a novel 0.9 kb PACAP transcript,
      which appeared similar in size to a form present in testes. Using reverse
      transcription PCR and 3' RACE studies, we demonstrated that the 0.9 kb PACAP mRNA
      in depolarized SCG neurons was not identical to the testicular PACAP mRNA, but
      represented shortened, more stable, forms of the 2.2 kb transcript resulting from
      alternative upstream polyadenylation site usage. These results demonstrate that
      post-transcriptional mechanisms play important roles in determining cellular
      PACAP levels and provide several important insights. For example, alternative
      upstream polyadenylation can elicit a major influence on the amount of bioactive
      peptide that can by synthesized, since short 3' UTR transcripts are usually more
      stable due to elimination of destabilizing elements present in the longer
      messages. In cells such as testicular germ cells, which have restricted
      transcriptional periods, stable mRNAs allow longer translational events and
      extended periods of peptide production. The neuronal PACAP system adopts a
      similar post-transcriptional strategy following neuronal depolarization, and
      although the roles of PACAP remain unclear, this suggests important roles for
      PACAP peptides during increased neuronal activity. Additionally, unlike
      alternative polyadenylation described for many genes, alternative site usage in
      the proPACAP transcript does not result from alternative splicing. The mechanism
      of alternative site usage may be related to changes in the expression and binding
      of polyadenylation factors to the short and long 3' UTR proPACAP sites leading to
      production of more stable transcripts and increased PACAP precursor biosynthesis.
      The implications of increased PACAP production following altered
      neurophysiological states and the mechanisms underlying alternative
      polyadenylation site choice are important considerations for future inquiries.

PMID- 9928032
TI  - A model of the receptors in the VIP receptor family.

PMID- 9928034
TI  - Constitutive activation of the human VIP1 receptor.

PMID- 9928033
TI  - Site-directed mutagenesis of human VIP1 versus VIP2 receptors.

PMID- 9928035
TI  - Construction of chimeras between human VIP1 and secretin receptors:
      identification of receptor domains involved in selectivity towards VIP, secretin,
      and PACAP.

PMID- 9928036
TI  - Involvement of a Pit-1 binding site in the regulation of the rat somatostatin
      receptor 1 gene expression.
AB  - It was shown that at least four regions in the 2.2 kb upstream DNA of the sst1
      gene are important for the cell type-specific promoter activity in GH3 and RIN
      cells. Moreover, the 48 bp region located between -165 to -117 harbors positive
      regulatory elements that are active in RIN and GH3 cells. This region is
      recognized by the pituitary-specific transcription factor Pit-1. It is therefore
      concluded that Pit-1 represents a major regulator of GH secretion at the genetic
      level by regulating transcriptional activity not only of the GH gene itself but
      also of the genes for the receptors that mediate stimulation and inhibition of GH
      secretion.

PMID- 9928037
TI  - Relaxant responses of VIP and PACAP in rat ileum: receptors and adaptive
      supersensitivity.

PMID- 9928038
TI  - VIP1 and VIP2 receptors but not PVR1 mediate the effect of VIP/PACAP on cytokine
      production in T lymphocytes.
AB  - Neuropeptides such as VIP and PACAP produced or released within the lymphoid
      microenvironment modulate the immune response through their effect on immune
      cells bearing specific receptors. In response to antigenic stimulation, CD4+ T
      cells, and to a lesser degree CD8+ T cells, produce cytokines that play essential
      roles in the initiation and amplification of various immune responses. VIP/PACAP
      downregulate the expression of a variety of cytokines such as IL-2, IL-4, and IL
      10, by directly affecting the cytokine-producing T cells. Since three types of
      receptors, PVR1 (the PACAP-preferring receptor), PVR2 (VIP1), and PVR3 (VIP2)
      bind PACAP/VIP, this study investigated the expression of these receptors in
      murine T lymphocytes and their role in mediating the inhibition of cytokines.
      VIP1 and VIP2 agonists, but not PVR1 agonists, inhibit IL-2, IL-4, and IL-10
      production, and VIP1 and VIP2, but not PVR1 mRNA, were identified in purified
      CD4+ and CD8+ splenic T cells. In addition, immunofluorescence studies confirmed
      the presence of VIP1 and VIP2 on CD4+ and CD8+ T cells. These results indicate
      that both subsets of peripheral T lymphocytes express VIP1 and VIP2, but not PVR1
      receptors, and that the inhibitory effect of VIP/PACAP on IL-2 and IL-10
      production is mediated by both VIP1 and VIP2 receptors.

PMID- 9928039
TI  - Distribution and ultrastructural localization of pituitary adenylate cyclase
      activating polypeptide (PACAP) and its receptor in the rat retina.

PMID- 9928040
TI  - Autoradiographic visualization of the receptor subclasses for vasoactive
      intestinal polypeptide (VIP) in rat brain.

PMID- 9928041
TI  - Pituitary adenylate cyclase-activating polypeptide receptors in the fetal human
      adrenal gland.

PMID- 9928042
TI  - Neuropeptides in developmental tumors of the central and peripheral nervous
      system.

PMID- 9928043
TI  - PACAP increases cytosolic calcium in vasopressin neurons: synergism with
      noradrenaline.

PMID- 9928044
TI  - Effect of PACAP-27 on adenylate cyclase in ductal and acinar cells of rat
      submandibular gland.

PMID- 9928045
TI  - Distribution and ultrastructural localization of PACAP receptors in the rat
      pancreatic islets.

PMID- 9928046
TI  - Protein kinase A inhibition and PACAP-induced insulin secretion in HIT-T15 cells.

PMID- 9928047
TI  - PACAP and GLP-1 protect islet beta-cells against Ca2+ toxicity induced by high
      K+.

PMID- 9928048
TI  - Autocrine action of PACAP in islets augments glucose-induced insulin secretion.

PMID- 9928049
TI  - A target cell to oxyntomodulin and glicentin: the antral smooth muscle cell.

PMID- 9928050
TI  - Effects of PACAP/VIP/secretin on pancreatic and gastrointestinal blood flow in
      conscious dogs.

PMID- 9928051
TI  - Pituitary adenylate cyclase activating polypeptide stimulates insulin secretion
      in a glucose-dependent manner in vivo.

PMID- 9928052
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cAMP
      formation and growth hormone release from chicken anterior pituitary cells.

PMID- 9928053
TI  - Localization of pituitary adenylate cyclase-activating polypeptide in the central
      nervous system of the European eel Anguilla anguilla: stimulatory effect of PACAP
      on GH secretion.

PMID- 9928054
TI  - Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on tyrosine
      hydroxylase gene expression in the rat adrenal medulla.

PMID- 9928055
TI  - The stimulatory effect of VIP and PACAP on adrenal aldosterone release.

PMID- 9928056
TI  - Evidence for PACAP to be an autocrine factor on gonadotrope cells.
AB  - In summary, PACAP actions on gonadotrope cells are schematically outlined in
      FIGURE 5. PACAP is produced by and secreted from gonadotropes. The peptide
      increases LH release in an autocrine manner by a direct stimulatory action via
      the PACAP receptor and, as suggested by Culler and Paschall, by amplification of
      the LHRH stimulus. Hence, our data support the hypothesis that PACAP acts as an
      autocrine regulator on gonadotrope cell function.

PMID- 9928057
TI  - Peptidergic component of non-adrenergic non-cholinergic relaxation of the rat
      gastric fundus.

PMID- 9928058
TI  - Effect of VIP and PACAP on vascular and luminal release of serotonin from
      isolated perfused rat duodenum.
AB  - Effects of CCK, VIP, PACAP38, and PACAP27 on the release of 5HT into the
      intestinal lumen and into the portal circulation were examined in in vivo
      experiments of isolated rat duodenum perfused vascularly and luminally. VIP,
      PACAP 38 and 27 reduced the release of 5HT into the lumen but did not affect the
      vascular release of 5HT. These effects were not affected by the presence of
      atropine, hexamethonium, or TTX, suggesting that VIP, PACAP 38 and 27 exert a
      direct inhibitory effect on the luminal release of 5HT from the EC cells. Nitric
      oxide synthase inhibitor, NG-nitro-L-arginine, antagonized the inhibitory effects
      of VIP, PACAP 38 and 27, suggesting that nitric oxide seems to be essential to
      exert the inhibitory action of VIP and PACAPs on the release of 5HT into the
      intestinal lumen from the EC cells.

PMID- 9928059
TI  - Sites of actions of contractile and relaxant effects of pituitary adenylate
      cyclase activating peptide (PACAP) in the internal anal sphincter smooth muscle.
AB  - In summary, PACAP exerts a biphasic effect (an initial contraction followed by a
      relaxation) in the IAS. The initial contractile effect with higher concentrations
      of PACAP was found to be mediated by the activation of PACAP receptor at the
      substance P-containing nerve terminals. The PACAP receptor(s) responsible for the
      inhibitory action of the neuropeptide is(are) hypothesized to be present in the
      IAS smooth muscle cells and on the myenteric nerve terminals. The exact nature
      and the role of PACAP and the PACAP receptors in the inhibitory
      neurotransmission, the relationship of PACAP receptors with substance P
      containing neurons and IAS smooth muscle cells, and interactions with the NOS
      pathway and VIP remain to be determined.

PMID- 9928060
TI  - Effect of sodium depletion by frusemide on tissue concentrations and metabolism
      of VIP.

PMID- 9928061
TI  - Neuromodulator role of VIP in recovery of rat behavior and brain
      neurotransmitters level after frontal lobectomy.

PMID- 9928062
TI  - Immunohistochemical evidence for PACAP and VIP interaction with met-enkephalin
      and CRF containing neurons in the bed nucleus of the stria terminalis.

PMID- 9928063
TI  - Distribution and somatotopical localization of pituitary adenylate cyclase
      activating polypeptide (PACAP) in the trigeminal ganglion of cats and rats.

PMID- 9928064
TI  - Prenatal expression of pituitary adenylate cyclase activating polypeptide (PACAP)
      in autonomic and sensory ganglia and spinal cord of rat embryos.

PMID- 9928065
TI  - VIP and NPY expression during differentiation of cholinergic and noradrenergic
      sympathetic neurons.

PMID- 9928066
TI  - PACAP in visceral afferent nerves supplying the rat digestive and urinary tracts.

PMID- 9928067
TI  - Galanin controls excitability of the brain.

PMID- 9928068
TI  - Vasoactive intestinal peptide supports spontaneous and induced migration of human
      keratinocytes and the colonization of an artificial polyurethane matrix.

PMID- 9928069
TI  - The stimulatory effect of VIP on progesterone release in rats after
      adrenalectomy, ovariectomy, and hysterectomy: influence of VIP and PACAP38 on
      progesterone release in rats after ovariectomy and hysterectomy.

PMID- 9928070
TI  - Characterization of a PACAP-like immunoreactive component in red ginseng root.

PMID- 9928071
TI  - The effect of vasoactive intestinal polypeptide and pituitary adenylate cyclase
      activating polypeptide on tolerance to morphine and alcohol in mice.

PMID- 9928072
TI  - The effect of vasoactive intestinal peptide (VIP) and inhibition of nitric oxide
      on renal tissue injury of rats exposed to hemorrhagic ischemia and retransfusion:
      a possible interaction mechanism among mast cells and tissue histamine.

PMID- 9928073
TI  - Enhancement of systemic and pulmonary vasoconstriction by beta-amyloid peptides
      and its suppression by vasoactive intestinal peptide.
AB  - (1) A beta peptides potentiate vasoconstriction, caused by norepinephrine, and
      possibly other endogenous vasoconstrictors. If this potentiation occurs in the
      cerebral circulation, close to sites of A beta deposition in AD brains, the
      enhanced vasoconstriction could result in neuronal ischemia and death. (2) By
      neutralizing this deleterious effect of A beta, and through other neuroprotective
      mechanisms, VIP may provide an important defense against neuronal loss in AD.

PMID- 9928074
TI  - The effect of vasoactive intestinal peptide (VIP) and inhibition of nitric oxide
      synthase on survival rate in rats exposed to endotoxin shock.

PMID- 9928075
TI  - Role of PACAP in the regulation of gonadotroph hormone secretion during
      ontogenesis: a single neonatal injection of PACAP delays puberty and its
      intracerebroventricular administration before the critical period of proestrous
      stage blocks ovulation in adulthood.

PMID- 9928076
TI  - Is an intravenous bolus injection required prior to initiating slow intravenous
      infusion of PACAP38 for prevention of neuronal death induced by global ischemia?
      The possible presence of a binding protein for PACAP38 in blood.

PMID- 9928077
TI  - Effect of rat glicentin on intestinal adaptation in small intestine-resected
      rats.

PMID- 9928078
TI  - Active site flexibility in enzyme catalysis.
AB  - The inactivation of a number of enzymes during denaturation by physical and
      chemical factors precedes detectable global conformational changes of the
      molecules as monitored by conventional methods. It was suggested that the enzyme
      active site is more flexible and more sensitive to denaturation than the molecule
      as a whole. The well-known "induced fit" hypothesis by Koshland implies
      multiconformational states of enzymes in equilibrium with one another easily
      perturbed by ligands. Each intermediary step during the entire catalytic process
      may require the molecule to be in a particular conformation state; rapid
      interconversion between the different conformation states may well be involved in
      the catalytic process. As a relative fragile and consequently flexible active
      site has now been envisaged, it appears that a rapid cycling of the different
      active site conformation states is essential for the full expression of enzyme
      activity.

PMID- 9928079
TI  - Protein disulfide isomerase assists protein folding as both an isomerase and a
      chaperone.
AB  - Protein disulfide isomerase (PDI) is the physiological catalyst of native
      disulfide bond formation of nascent peptides in the cells. As a foldase, PDI has
      both isomerase and chaperone activities. The chaperone activity is intrinsic and
      independent of its isomerase activity. Both chaperone and isomerase activities
      are required for PDI to assist folding of denatured and reduced disulfide
      containing proteins. PDI may have great applications in protein production by
      bioengineering for its function as a foldase.

PMID- 9928080
TI  - A toolbox of recombinant lipases for industrial applications.
AB  - We created a toolbox of recombinant, microbial lipases, which allows us in
      combination with a lipase database to choose among the overexpressed lipases the
      most appropriate for a specific application and to improve it further via
      mutagenesis. By systematic comparison of geometry and properties of the scissile
      fatty acid binding site of five representative lipases of each family of
      structurally homologous lipases, three subgroups can be defined. Hence, efficient
      expression systems for the functional production of large amounts of microbial
      lipases, representing different lipase subgroups, were developed. In particular,
      recombinant lipases from Bacillus thermocatenulatus and Pseudomonas cepacia were
      functionally overexpressed in E. coli. The lipase genes from Geotrichum candidum
      CMICC 335426 and Rhizopus oryzae were overexpressed in Pichia pastoris. Due to an
      unusual codon usage that prevents heterologous expression, the LIP1 gene (1647
      nt) of Candida rugosa was completely synthesized and overexpressed in Pichia
      pastoris.

PMID- 9928081
TI  - Biosensors for environmental monitoring.
AB  - Environmental monitoring is of great importance for its protection. Conventional
      monitoring methods are often slow and complex and require expensive equipment,
      making them unsuitable for in situ, real-time monitoring of pollutants.
      Biosensors based on a combination of a biological sensing element and an
      electronic signal-transducing element are alternative methods to conventional
      ones. Biosensors have a number of advantages, such as high selectivity, high
      stability, and short response time. Various kinds of biosensors have been
      developed and employed for detection of pollutants such as phosphate, cyanide,
      and herbicides. Some of these have already been exploited as real-time monitoring
      in situ. In this article, some of the applications of biosensors for
      environmental control are described.

PMID- 9928082
TI  - Enzymatic modification of natural compounds with pharmacological properties.
AB  - Glycosides of various classes of natural products are widely distributed in
      nature, where they are often present esterified with aliphatic and aromatic acids
      at specific OH's of their sugar moieties. Many of these compounds are
      pharmacologically important molecules or possess other interesting properties.
      For instance, ginsenosides (e.g., 3) are therapeutic dammarane-type
      oligoglycosides isolated from the water-soluble portion of the dried roots and
      leaves of Panax ginseng C.A. Meyer (Aralianceae), a plant widely used in
      traditional Chinese medicine. In recent years, we have exploited the
      regioselectivity of lipases and proteases in organic solvents for the synthesis
      of specific esters of ginsenosides as well as the selectivity of the beta-1,4
      galactosyltransferase from bovine colostrum to obtain new glycosyl derivatives of
      these compounds. The application of these two enzymatic methodologies has also
      been exemplified with other natural compounds with pharmacological properties:
      digitonin (5), colchicoside (6), and flavonoid glycosides.

PMID- 9928083
TI  - Chiral alcohol synthesis with microbial carbonyl reductases in a water-organic
      solvent two-phase system.
AB  - Production of chiral 4-chloro-3-hydroxybutanoate ethyl esters (CHBE) was
      performed through microbial asymmetric reduction of 4-chloroacetoacetate ethyl
      ester (CAAE). The enzymes reducing CAAE to (R)- and (S)-CHBE were found to be
      produced by Sporobolomyces salmonicolor and Candida magnoliae, respectively. The
      enzyme of S. salmonicolor is a novel NADPH-dependent aldehyde reductase (AR)
      belonging to the aldo-keto reductase superfamily. When AR-overproducing
      Escherichia coli transformant cells or C. magnoliae cells were incubated in an
      organic solvent-water two-phase system, 300 or 90 mg/mL of CAAE was almost
      stoichiometrically converted to (R)- or (S)-CHBE (> 92% ee), respectively.

PMID- 9928085
TI  - Production of "neometalloenzymes" by de novo biosynthesis. New ELISA method for
      their characterization.
AB  - Several approaches known for producing "neometalloenzymes" are classified into
      two categories: protein engineering using antibodies as starting materials and
      "de novo" biosynthesis of metal-binding antibodies with potential catalytic metal
      binding structure. This latter approach is chosen in this study. Polyclonal anti
      zinc-iminodiacetate [IDA-Zn(II)] antibodies are produced in rabbits and mice.
      Because of the absolute need for the unequivocal screening of the hapten [IDA
      Zn(II)] specific antibodies, a new ELISA method was developed using a biheaded
      polyethylene glycol with biotin on one end and the hapten on the other end. The
      parameters for optimizing the immunization and the ELISA technique are discussed
      and the method is validated with rabbit and mice sera.

PMID- 9928084
TI  - New strategy of thrombolysis. Conjunctive effect of plasminogen activators with
      different pharmacokinetic profile.
AB  - Combined actions of native and prolonged thrombolytics allow the use of lower
      doses and simplified schemes of administration, thus yielding significant results
      in experimental therapy regarding the efficacy and safety of thrombolysis.
      Development of prolonged forms of plasminogen activators and testing their effect
      in combination with the thrombolysis trigger are well founded and of current
      interest. Thrombolytic compositions on the basis of short- and long-term-acting
      plasminogen activators appear to be promising and potentially eligible for bolus
      administration.

PMID- 9928086
TI  - Screening of inhibitory monoclonal antibodies. A critical step for producing anti
      idiotypic catalytic antibodies.
AB  - In accord with the original approach that we proposed, catalytic antibodies may
      be produced by using the anti-idiotypic pathway according to antigen/antibody
      complementarity rules. The generation and screening of the idiotypic Ab1, the
      central point on which are anchored the interactions with both the antigen
      (enzyme) and the anti-idiotypic abzyme, represent a crucial step for the success
      of this approach. We herein propose to describe a strategy for which we have
      developed a number of assays, aiming at selecting the proper Ab1, with desired
      features, likely to elicit an anti-idiotypic catalytic antibody. beta-Lactamase
      from Bacillus cereus was chosen as the example illustrating our arguments.

PMID- 9928087
TI  - Properties of artificial proteins with random sequences.
AB  - A library of artificial proteins of 141 amino acid residues, of which 95 are
      random and which include 20 kinds of amino acids, was prepared. As the properties
      of the artificial random proteins are free from the evolutionary constraint, they
      can be used as a standard to discriminate the specialized properties of natural
      proteins. Out of the 25 identified random proteins, 5 are soluble in the cell
      lysate, indicating that about 20% of the random proteins expressed in Escherichia
      coli are expected to be soluble. Therefore, as natural soluble or insoluble
      proteins can arise from the line of soluble or insoluble ancestry, respectively,
      solubility does not seem a specialized property of natural proteins. The soluble
      random proteins RP3-42 and RP3-45 were purified and their properties were
      investigated.

PMID- 9928088
TI  - A selenium-containing abzyme, the activity of which surpassed the level of native
      glutathione peroxidase.
AB  - Using two different glutathione derivatives as hapten, we have prepared two
      abzymes, which display glutathione peroxidase (GPX) activity. Their GPX
      activities are 0.2 and 1.6 times that of natural GPX from rabbit liver,
      respectively. Selenium content analysis indicates that the activity difference
      between the two abzymes is possibly attributed to the conformation difference of
      the abzymes.

PMID- 9928089
TI  - Directed evolution of new enzymes and pathways for environmental biocatalysis.
AB  - Biocatalysis is important in both natural and engineered environments. The major
      global reactions in the biospheric cycling of carbon, nitrogen, and other
      elements are catalyzed by microorganisms. The global carbon cycle includes
      millions of organic compounds that are made by plants, microorganisms, and
      organic chemists. Most of those compounds are transformed by microbial enzymes.
      Degradative metabolism is known as catabolism and yields principally carbon
      dioxide, methane, or biomass. Microbial catabolic enzymes are a great resource
      for biotechnology. They are the building blocks for engineering novel metabolic
      pathways and evolving improved enzymes in the laboratory. Two multicomponent
      bacterial oxygeneases, cytochrome P450cam and toluene dioxygenase, catalyze the
      dechlorination of polyhalogenated C2 compounds. Seven genes encoding those
      functional enzyme complexes were coexpressed in a Pseudomonas and shown to
      metabolize pentachloreothane to nonhalogenated organic acids that were
      metabolized further to carbon dioxide. In another example, the enzyme catalyzing
      the dechlorination of the herbicide atrazine was subjected to iterative DNA
      shuffling to produce mutations. By using a plate screening assay, mutated
      atrazine chlorohydrolase that catalyzed a more rapid dechlorination of atrazine
      was obtained. The mutant genes were sequences and found to encode up to 11 amino
      acid changes. Atrazine chlorohydrolase is currently being used in a model
      municipal water treatment system to test the feasibility of using enzymes for
      atrazine decontamination. These data suggest that the natural diversity of
      bacterial catabolic enzymes provides the starting point for improved biocatalytic
      systems that meet the needs of commercial applications.

PMID- 9928091
TI  - Effect of reductive alkylation of Candida rugosa lipase on its enantioselective
      esterification reaction.

PMID- 9928090
TI  - Fighting nerve agent chemical weapons with enzyme technology.
AB  - The extreme toxicity of organophosphorous-based compounds has been known since
      the late 1930s. Starting in the mid-1940s, many nations throughout the world have
      been producing large quantities of organophosphorous (OP) nerve agents. Huge
      stockpiles of nerve agents have since developed. There are reportedly more than
      200,000 tons of nerve agents in existence worldwide. There is an obvious need for
      protective clothing capable of guarding an individual from exposure to OP
      chemical weapons. Also, chemical processes that can effectively demilitarize and
      detoxify stored nerve agents are in great demand. The new and widely publicized
      Chemical Weapons Treaty requires such processes to soon be in place throughout
      the world. Biotechnology may provide the tools necessary to make such processes
      not only possible, but quite efficient in reducing the nerve agent dilemma. The
      following paper discusses some of the history in developing enzyme technology
      against nerve agents. Our laboratory has interest in enhancing the productivity
      and potential utility of these systems in both demilitarization and
      decontamination applications. Freeze-dried nerve agent-hydrolyzing enzyme
      preparations have been shown to be effective in decontaminating gaseous nerve
      agents. The direct incorporation of nerve agent-hydrolyzing enzymes within cross
      linked polyurethane foam matrices during polymer synthesis has been shown to
      dramatically enhance the productivity of two different enzyme systems. The future
      goal of such work lies in building a bridge between the clinical application of
      nerve agent-hydrolyzing enzymes and practical processing techniques that may take
      advantage of the initial results already achieved in the laboratory.

PMID- 9928092
TI  - Proteolysis of aggregated fibronectin. A model for in vivo matrix degradation.

PMID- 9928093
TI  - Glucosylation by dextransucrase. Modeling of reaction kinetics and unconventional
      products.

PMID- 9928094
TI  - Production, properties, and application of xylanase from Aspergillus niger A3.

PMID- 9928095
TI  - Stability in organic solvent mixtures of beta-glucosidase and beta
      fructofuranosidase as dry powder and entrapped in poly-HEMA.

PMID- 9928096
TI  - Inactivation of enzymes by inert gas bubbling. A kinetic study.

PMID- 9928097
TI  - Cloning, sequencing, and expression in Escherichia coli of D-hydantoinase gene
      from Pseudomonas putida.

PMID- 9928098
TI  - G-type nerve agent decontamination by Alteromonas prolidase.

PMID- 9928099
TI  - Lipase-catalyzed syntheses of monoglycerides by hydrolysis of soybean oil in
      AOT/isooctane reversed micelles.

PMID- 9928101
TI  - Growth-stimulating effect of Shochu wastewater on lactic acid bacteria and
      bifidobacteria.

PMID- 9928100
TI  - Study of abzymes with cytochrome P-450 catalytic activity.

PMID- 9928102
TI  - Kinetic studies of abzyme with glutathione peroxidase activity.

PMID- 9928103
TI  - Antioxidant effects of superoxide dismutase and horseradish peroxidase on lipid
      peroxidation.

PMID- 9928104
TI  - A convenient enzymatic procedure for the production of aldose-free D-tagatose.

PMID- 9928105
TI  - Application of thick film technology in mass production of biosensors.

PMID- 9928107
TI  - Low-calorie structured lipid synthesis by lipase-catalyzed transesterification.

PMID- 9928108
TI  - Catalytic properties of lipase entrapped in alkyl-substituted organic silicates.

PMID- 9928109
TI  - Reducing side reactions in protease-catalyzed tripeptide (RGD) synthesis.

PMID- 9928106
TI  - cDNA cloning and heterologous expression of mouse CYP2G1.

PMID- 9928111
TI  - Biochemical properties of thermostable D-hydantoinase from Bacillus
      thermocatenulatus GH-2.

PMID- 9928112
TI  - Novel bacteriocin of Pediococcus sp. ISK-1 isolated from well-aged bed of
      fermented rice bran.

PMID- 9928110
TI  - Engineering the thermostable D-hydantoinases from two thermophilic Bacilli based
      on their primary structures.

PMID- 9928113
TI  - Converting T4 phage lysozyme into a transglycosidase.

PMID- 9928114
TI  - A cultivation strategy of recombinant Escherichia coli for mass production of
      thermostable D-hydantoinase.

PMID- 9928115
TI  - Development of recombinant bacteria for the degradation of dibenzothiophene.

PMID- 9928116
TI  - Conformation changes of alcohol dehydrogenase from baker's yeast (YADH) induced
      by hydrostatic pressure.

PMID- 9928117
TI  - Purification and properties of 3 alpha-hydroxysteroid dehydrogenase and 3-keto-5
      beta-steroid-delta 4-dehydrogenase.

PMID- 9928118
TI  - Thrombolytic effect after sequential double-bolus administration of tissue
      plasminogen activator and urokinase-fibrinogen conjugate into dogs with venous
      thrombosis.

PMID- 9928119
TI  - Enzymatic synthesis of edible surfactants from food ingredients.

PMID- 9928120
TI  - Purification, identification, and effective production of a peptide antibiotic
      produced by Lactococcus lactis IO-1 (JCM 7638).

PMID- 9928121
TI  - Engineering of enzyme monolayer for industrial biocatalysis. An overview.

PMID- 9928122
TI  - Strategies to an efficient enzymatic production of xylitol.

PMID- 9928123
TI  - Enzymatic synthesis of mannitol. Reaction engineering for a recombinant mannitol
      dehydrogenase.

PMID- 9928125
TI  - Enzymatic and structural approaches of the thermolysin mechanism in glycerol
      containing media.

PMID- 9928124
TI  - Sorbitol oxidase from microorganisms.

PMID- 9928126
TI  - Biomodification of selected tropical oils for the production of specialty fats
      and oils.

PMID- 9928127
TI  - Enzymatic modification of straw pulp and characterization of alkaline xylanases
      from Pseudomonas sp.

PMID- 9928128
TI  - Development of an ELISA for detection of parathion, carbofuran, and 2,4
      dichlorophenoxyacetic acid in water, soil, vegetables, and fruits.

PMID- 9928130
TI  - Water activity effect on lipase immobilized onto different compositions of
      poly(HEMA-MMA).

PMID- 9928129
TI  - Purification of a fusion protein using the family VI cellulose-binding domain of
      Clostridium stercorarium XynA.

PMID- 9928131
TI  - Use of a laccase-column for flow-injection calorimetry.

PMID- 9928132
TI  - Enhancement effect of reverse micelles on enzymatic synthesis of cephalexin.

PMID- 9928133
TI  - Levansucrase of Rahnella aquatilis ATCC33071. Gene cloning, expression, and levan
      formation.

PMID- 9928135
TI  - Totally enzymatic synthesis of peptides. Penicillin acylase-catalyzed protection
      and deprotection of amino groups as important building blocks of this strategy.

PMID- 9928134
TI  - Upward shift of thermotolerance of cold water fish and mammalian trypsins upon
      chemical modification.

PMID- 9928136
TI  - Molecular breeding of polysaccharide-utilizing yeast cells by cell surface
      engineering.

PMID- 9928137
TI  - Enantioselective esterification of racemic naproxen catalyzed by immobilized
      lipase in a microaqueous system.

PMID- 9928138
TI  - High-affinity peptide ligands for pancreatic alpha-amylase by phage display.

PMID- 9928139
TI  - Improving the catalytic activity of phenylalanine aminotransferase of Escherichia
      coli by site-specific mutation.

PMID- 9928140
TI  - Effect of exogenous electron donors and water-soluble polymers on the propene
      epoxidizing activity of Methylomonas Z201 cells.

PMID- 9928141
TI  - Effect of water content on enzyme activity and enantioselectivity of lipase
      catalyzed esterification of racemic ibuprofen in organic solvents.

PMID- 9928142
TI  - Construction of urea-resistant Staphylococcus aureus V8 protease derivatives and
      application in the releasing of peptide hormones from fusion proteins.

PMID- 9928143
TI  - Screening of the fungus whose multienzyme system has catalytic detoxification
      activity towards aflatoxin B1 (Part I).

PMID- 9928144
TI  - Armillariella tabescen enzymatic detoxification of aflatoxin B1 (Part II).

PMID- 9928145
TI  - Armillariella tabescen enzymatic detoxification of aflatoxin B1. Part III.
      Immobilized enzymatic detoxification.

PMID- 9928146
TI  - Analysis of glycolysis relevant compounds in saliva by microbiosensors.

PMID- 9928147
TI  - Extraction and some properties of soluble methane monooxygenase of Methylosinus
      trichosporium IMV 3011.

PMID- 9928148
TI  - Biochemical characterization of alpha-aspartyl dipeptidase. Cloning and
      expression of its gene.

PMID- 9928150
TI  - Studies on the properties of mutants of aspartase from Escherichia coli W.

PMID- 9928149
TI  - Studies on the amino acid residues of the active site of alpha-aspartyl
      dipeptidase.

PMID- 9928151
TI  - The design and construction of a new nucleozyme.

PMID- 9928152
TI  - Bioactive small peptides from soybean protein.

PMID- 9928153
TI  - Lipase-catalyzed enantioselective transesterification of cyanohydrins for the
      synthesis of (S)-alpha-cyano-3-phenoxybenzyl acetate.

PMID- 9928154
TI  - Kinetics of butyl acetate synthesis by lipase-catalyzed transesterification in
      hexane.

PMID- 9928156
TI  - Analysis of selected regulatory pathways for rat galanin gene transcription and
      their suitability as putative models for negative regulation by NGF.
AB  - Nerve growth factor (NGF) is known to negatively regulate the transcription of
      the rat galanin gene both in vivo and in vitro in dorsal root ganglion neurons,
      yet it is unclear how this regulation actually occurs. We propose here several
      possible pathways whereby NGF could interact to exert negative control on galanin
      regulation. These include: (1) repression of AP1-mediated transcription, (2)
      repression of nuclear binding protein-mediated transcription, and (3) repression
      of cytokine-mediated transcription. Although not enough data are available for
      speculation on which, if any, of these pathways is most relevant for NGF
      repression of galanin transcription, the mechanisms we describe can provide
      putative models for regulatory pathways. From here we can carry out further
      experiments that may help to elucidate the possible mechanisms of NGF repression
      in vivo.

PMID- 9928155
TI  - Transcriptional control of the galanin gene. Tissue-specific expression and
      induction by NGF, protein kinase C, and estrogen.
AB  - Galanin is a neuropeptide widely expressed in the central and peripheral nervous
      system where it acts as a neurotransmitter/neuromodulator and possibly an
      immunoregulator and growth factor. Galanin gene expression is highly regulated
      during development and by certain hormones and injury situations. We have
      examined transcriptional control mechanisms for this gene using chimeric bovine
      galanin/luciferase reporter genes. These were analyzed in cultured cells and in
      transgenic mice. The studies reveal that enhancer and silencer sequences are
      involved in conferring cell- and tissue-specific expression, and that specific
      elements close to the promoter are responsible for nerve growth factor and
      protein kinase C induction. So far, the studies have not revealed sequences on
      the bovine gene that mediate the action of estrogen.

PMID- 9928158
TI  - Galanin in normal and hyperplastic anterior pituitary cells. From pituitary tumor
      cell lines to transgenic mice.
AB  - Studies on the regulation of galanin expression in the epithelial cells of the
      anterior pituitary gland have provided a wealth of insight into the cellular and
      molecular biology of this unique peptide. Galanin is localized within
      subpopulations of specific pituitary cell types, and hypothalamic as well as
      gonadal factors including dopamine, somatostatin, thyrotropin-releasing hormone,
      growth hormone-releasing hormone (GHRH), estrogen, and progesterone dynamically
      regulate its expression and release. Galanin gene expression and peptide
      secretion are markedly increased in estrogen-induced prolactinomas, wherein
      galanin serves as both an autocrine and paracrine hormone regulating prolactin
      secretion. Galanin mRNA and peptide levels are also dramatically elevated in
      somatotroph adenomas of human GHRH transgenic mice. Moreover, galanin secretion
      is increased from the hyperplastic somatotrophs of hGHRH transgenic mice.
      However, not all pituitary adenomas are associated with increased galanin gene
      expression; galanin synthesis is repressed in 131I-induced thyrotroph adenomas.
      Thus, galanin acts locally to regulate pituitary hormone secretion and appears to
      act as a mitogenic factor to increase the proliferation of pituitary cells in a
      cell-type specific manner.

PMID- 9928157
TI  - Targeted disruption of the murine galanin gene.
AB  - The 29 amino acid neuropeptide galanin is widely distributed in the nervous and
      endocrine systems; highest levels of galanin synthesis and storage occur within
      the hypothalamus in the median eminence, but it is also abundantly expressed in
      the basal forebrain, the peripheral nervous system, and gut. To further define
      the role played by galanin in the peripheral nervous and endocrine systems, a
      mouse strain carrying a loss-of-function germ-line mutation of the galanin locus,
      engineered by targeted mutagenesis in embryonic stem cells, has been generated.
      The mutation removes the first five exons containing the entire coding region for
      the galanin peptide. Germ-line transmission of the disrupted galanin locus has
      been obtained, and the mutation has been bred to homozygosity on the inbred
      129O1aHsd background. Phenotypic analysis of mice lacking a functional galanin
      gene demonstrate that these animals are viable, grow normally, and can reproduce.
      A marked reduction in both the anterior pituitary prolactin content and in
      circulating plasma levels of the hormone is evident. Lactation is abolished along
      with abrogation of the proliferative response of the lactotroph to estrogen. The
      responses of sensory neurons to injury in the mutants are markedly impaired.
      Peripheral nerve regeneration is reduced with associated long-term functional
      deficits. There is a striking reduction in the development of chronic neuropathic
      pain. These two phenotypic changes may be explained, in part, by the observation
      that a subset of dorsal root ganglion neurons is lost in the mutant animals,
      implying a role for galanin as a trophic cell survival factor. These initial
      findings have important implications for our understanding and potential
      therapeutic treatment of (a) sensory nerve regeneration and neuropathic pain and
      (b) disordered pituitary proliferation and the development of prolactinoma.

PMID- 9928159
TI  - Structural organization and chromosomal localization of three human galanin
      receptor genes.
AB  - Human galanin receptor subtypes GALR1, GALR2, and GALR3 are encoded by separate
      genes that are located on human chromosomes 18q23, 17q25.3, and 22q13.1,
      respectively. The exon:intron organization of the gene encoding GALR2 (GALNR2)
      and GALR3 (GALNR3) is conserved, with exon 1 encoding the NH2-terminus to the end
      of transmembrane domain 3 and exon 2 encoding the remainder of the receptor, from
      the second intracellular loop to the COOH-terminus. This conservation of
      structural organization is indicative of a common evolutionary origin for GALNR2
      and GALNR3. The exon:intron organization of the gene encoding GALR1 (GALNR1) is
      different from that of GALNR2 and GALNR3, with exon 1 encoding the NH2-terminus
      to the end of transmembrane domain 5, exon 2 encoding the third intracellular
      loop, and exon 3 encoding the remainder of the receptor, from transmembrane
      domain 6 to the COOH-terminus. The structural organization of GALNR1 suggests
      convergent evolution for this gene and represents a structural organization that
      is unique among genes encoding G-protein-coupled receptors.

PMID- 9928160
TI  - Galanin causes Cl- secretion in the human colon. Potential significance of
      inflammation-associated NF-kappa B activation on galanin-1 receptor expression
      and function.
AB  - Galanin is widely distributed in enteric nerves and nerve terminals throughout
      the gastrointestinal (GI) tract. Within the GI tract galanin is best known for
      its ability to alter smooth muscle contractility and regulate intestinal
      motility. However, recent studies also indicate that galanin can modulate
      epithelial ion transport. We previously showed that epithelial cells lining the
      human GI tract, including those of colonic origin, express Gal1 galanin receptors
      (Gal1-R). We herein demonstrate that epithelial cells lining the human colon only
      express Gal1-R receptors and do not express other galanin receptor subtypes. We
      previously showed that Gal1-R expression was transcriptionally regulated by the
      transcription factor NF-kappa B. Consistent with this transcription factor being
      activated in a number of inflammatory conditions, we show increased colonic Gal1
      R expression in patients with colitis due to a variety of causes. To further
      evaluate the physiology of Gal1-R activation, we studied this receptor expressed
      by the human colon epithelial cell line T84. Gal1-R activation resulted in a dose
      dependent increase in Cl- secretion; whereas infection of T84 cells with
      pathogens known to activate NF-kappa B augmented Gal1-R expression and Cl-
      secretion. Thus, galanin acts as a secretagogue in epithelial cells lining the
      human colon, with alterations in Gal1-R expression possibly playing an important
      role in the diarrhea associated with various inflammatory processes affecting the
      GI tract.

PMID- 9928161
TI  - Mutagenesis study on human galanin receptor GalR1 reveals domains involved in
      ligand binding.
AB  - Many receptor mutants were generated and several NH2-terminally modified galanin
      analogs synthesized to define the regions of hGalR1 involved in galanin binding.
      Ligand binding properties and functionality of mutant receptors were evaluated.
      The His264Ala and Phe282Ala receptor mutants, although deficient in binding in
      the concentration range of galanin used, remained functional albeit at least 20
      fold less efficient than the wild-type receptor in the inhibition of stimulated
      cAMP production. Hence, His264 and Phe282 of hGalR1 are directly involved in
      galanin binding. NH2-terminal carboxylic acid analogs of galanin (1-16) have a
      very low affinity for the wild-type receptor, but substantially increased
      affinity for the Glu271Lys-hGalR1, suggesting that the NH2-terminus of galanin
      binds to the receptor near the transmembrane (TM) VI. Based on these findings and
      computer-aided molecular modeling, we propose a binding site model for the hGalR1
      receptor (possibly also for other galanin receptor subtypes): galanin binds with
      its NH2-terminus to the pocket between TM III and TM VI, Trp2 of galanin
      interacts with His264 of the receptor, and Tyr9 is involved in an aromatic
      aromatic type of interaction with Phe282 of ECIII of GalR1.

PMID- 9928162
TI  - Chemistry and molecular biology of galanin receptor ligands.

PMID- 9928163
TI  - Molecular biology and pharmacology of galanin receptors.
AB  - Galanin was first isolated 15 years ago. Diversity of galanin receptors has been
      suspected from the study of native tissues and functional responses to galanin
      and galanin-like peptides in vitro and in vivo. The recent application of
      molecular biologic techniques to clone galanin receptors has extended this
      diversity. So far, three galanin receptor subtypes, GALR1, GALR2, and GALR3, have
      been cloned from both human and rat. Their molecular structure, pharmacologic
      profiles, tissue distribution, and signal transduction properties have been
      partially elucidated.

PMID- 9928164
TI  - Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin
      receptor, in the control of pain perception.
AB  - We have identified a novel subtype of galanin receptor (GALR-2) in rat dorsal
      root ganglia and spinal cord. The open reading frame of GALR-2 is 1116
      nucleotides long, encoding a protein of 372 amino acids with a theoretical
      molecular mass of 40.7 kD. Membranes prepared from stable pools of 293 cells
      expressing GALR-2, but not wild-type 293 cells, demonstrated high affinity
      galanin binding sites. Rat galanin and galanin-related peptides M40, C7, M15, and
      galanin effectively competed for binding; peptide C7 demonstrated a lower
      affinity for rGALR-2, and all these peptides were agonists at rGALR-2 when
      assessed on a microphysiometer. Studies on the expression of GALR-2 in various
      tissues by Northern and in situ hybridization analyses suggest a low abundance
      but wide distribution of GALR-2 mRNA, including several discrete areas in brain
      and spinal cord and a high abundance in the dorsal root ganglia.

PMID- 9928165
TI  - Distribution and characterization of the cell types expressing GALR2 mRNA in
      brain and pituitary gland.
AB  - The neuropeptide galanin mediates its activities through G-protein-coupled
      receptors, and three receptor subtypes have been described with distinctly
      different patterns of regional tissue expression. GALR1 is predominantly
      expressed in basal forebrain, hypothalamus, as well as spinal cord. GALR2 has a
      wider distribution in brain and is also present in the pituitary gland and
      peripheral tissues. GALR3 has been found to be widely distributed at low
      abundance. We examined the distribution of GALR2 in rat brain and pituitary by in
      situ hybridization histochemistry and found it abundant in regions of
      hippocampus, piriform and entorhinal cortex, basal nucleus of the accessory
      olfactory tract, amygdala, hypothalamic nuclei, Purkinje cells, and discrete
      brainstem nuclei. It is also highly expressed in the intermediate and anterior
      lobes of the pituitary. Using combined in situ hybridization immunohistochemistry
      we characterized the neurotransmitter and hormonal phenotype of cells expressing
      GALR2 mRNA in the hypothalamus and pituitary gland. Our findings suggest GALR2 is
      a receptor mediating important functions of galanin in the hypothalamic-pituitary
      axis and may also play a role in hippocampal and cerebellar function.

PMID- 9928166
TI  - Endocrine and gastrointestinal action of galanin.

PMID- 9928167
TI  - Role of galanin in the gastrointestinal sphincters.
AB  - Galanin was present and exerted potent effects in all the gastrointestinal
      sphincters examined. Galanin-immunoreactive nerve fibers and neurons are present
      in both the myenteric and submucosal plexuses of sphincters. The neuropeptide
      exerts diverse effects in different sphincteric smooth muscles that may be
      species specific. For example, in the lower esophageal sphincter, it may cause an
      increase in basal tone and suppression of nonadrenergic noncholinergic (NANC)
      nerve-mediated relaxation. On the contrary, in the internal anal sphincter (IAS),
      the predominant effect of galanin is to cause smooth muscle relaxation and
      augmentation of NANC nerve-mediated relaxation. In other sphincters, galanin may
      either have no effect or cause either an increase or a decrease in basal tone.
      Most of the actions of galanin on basal smooth muscle sphincteric tone are due to
      its actions directly on smooth muscle cells. However, some of the relaxant
      actions of the peptide may also be due to activation of NANC inhibitory neurons.
      The basic mechanism/s responsible for sphincteric smooth muscle contraction or
      relaxation in response to galanin have not been investigated. The suppressive as
      well as the augmentatory effects of galanin on NANC nerve-mediated sphincteric
      smooth muscle relaxation may be due to inhibition or facilitation, respectively,
      of the release of NANC inhibitory neurotransmitters such as nitric oxide and
      vasoactive intestinal polypeptide. Diverse effects in different gastrointestinal
      sphincters suggest a neuromodulatory rather than a neurotransmitter role of
      galanin and a significant role of the neuropeptide and putative antagonists in
      the pathophysiology and potential therapy of gastrointestinal motility disorders
      especially those affecting sphincteric function.

PMID- 9928168
TI  - Galanin activates an inwardly rectifying potassium conductance and inhibits a
      voltage-dependent calcium conductance in mudpuppy parasympathetic neurons.
AB  - Galanin-induced activation of an inwardly rectifying membrane potassium (K+)
      current and inhibition of barium current (IBa) were studied using whole cell
      voltage clamp recording techniques in parasympathetic neurons dissociated from
      the mudpuppy cardiac ganglion. Both activation of the K+ current and inhibition
      of IBa were concentration-dependent with an EC50 (or IC50) of approximately 35 nM
      and approximately 0.4 nM, respectively. Both actions of galanin were eliminated
      by pretreatment with pertussis toxin, which suggested involvement of Gi/Go
      protein activation. Galantide antagonized the galanin-induced activation of K+
      current with an IC50 equal to 4 nM. By contrast, galantide, by itself, inhibited
      IBa with an EC50 equal to 16 nM. Another galanin analog, M40, primarily
      antagonized the galanin-induced activation of K+ current, but in some cells, M40
      also acted as a weak agonist. M40, like galantide, inhibited IBa. The NH2
      terminal fragment galanin-(1-16) activated the K+ current and inhibited IBa,
      indicating that the first 16 amino acids of the galanin peptide were sufficient
      for both actions. In summary, it is postulated that the effects of galanin on
      mudpuppy parasympathetic neurons might be mediated by activation of two different
      subtypes of galanin receptor, one that regulates membrane K+ conductance and a
      second that modulates calcium conductance.

PMID- 9928169
TI  - Cardiovascular actions of galanin.

PMID- 9928170
TI  - LHRH and sexual dimorphism.
AB  - An increasing amount of evidences suggests that galanin plays an important role
      in the regulation of reproduction in the rat. Galanin is colocalized with
      luteinizing hormone-releasing hormone (LHRH) in a subset of LHRH neurons, and the
      pattern of coexpression is sexually dimorphic, with a higher incidence of
      colocalization and level of galanin mRNA and peptide expression in females than
      in males. Therefore, the role of galanin may be unique to females, as are the LH
      surge and ovulation. The colocalization of LHRH and galanin is neonatally
      determined by an epigenetic mechanism involving the testis, whereas the
      expression of galanin in adult LHRH neurons is upregulated by estrogen and
      modulated by progesterone. The action of these sex steroids requires intact
      neurotransmission towards LHRH neurons, indicating that their action is mediated
      by interneurons.

PMID- 9928171
TI  - Gonadal steroid-dependent GAL-IR cells within the medial preoptic nucleus (MPN)
      and the stimulatory effects of GAL within the MPN on sexual behaviors.
AB  - More GAL-I cells exist within sexually dimorphic cell groups of the medial
      preoptic nucleus (MPN) in male rate than females, a large percentage of estrogen
      concentrating cells within MPN cell groups are also GAL-immunoreactive (GAL-IR),
      and significantly more GAL-IR cells are visible with estrogen or its precursor,
      testosterone. Gonadal steroids also increase the size (diameter) of MPN GAL-IR
      cells and the number of GAL-IR cell processes within a portion of the MPN called
      the "GAL-IR MPOA plexus," which exists in males only. GAL microinjected into the
      MPN stimulated male-typical sexual behaviors, with more testosterone required in
      females than males. Immunoneutralization with anti-GAL serum inhibited male
      typical sexual behavior, indicating a role for endogenous GAL within the MPN.
      Microinjection of GAL into the MPN also stimulated female-typical sexual
      behaviors in estrogen-treated females and males, and GAL within the MPN
      dramatically overrode an inhibition of lordosis by dihydrotestosterone in rats of
      both sexes.

PMID- 9928172
TI  - Differential functions of hypothalamic galanin cell grows in the regulation of
      eating and body weight.
AB  - Evidence suggests that hypothalamic galanin (GAL) has a variety of functions
      related to energy and nutrient balance, reproduction, water balance, and
      neuroendocrine regulation. The focus of this chapter is the role of GAL in eating
      and body weight regulation. Findings described herein demonstrate that GAL, in a
      cell group of the anterior region of the paraventricular nucleus (aPVN) that
      projects to the median eminence, has a role in the control of fat intake, fat
      metabolism, and body fat. This function of aPVN GAL neurons is carried out in
      close relation to circulating insulin and glucose. Galanin-expressing perikarya
      in the medial preoptic area (MPOA) have a similar function, although GAL here
      operates in association with the female steroids estrogen and progesterone. These
      GAL cell groups of the aPVN and MPOA contrast with those in the arcuate nucleus
      as well as the magnocellular vasopressin-containing neurons of the PVN and
      supraoptic nucleus, which show no relation to fat balance. This evidence reveals
      differential functions for the distinct GAL neuronal cell groups of the
      hypothalamus.

PMID- 9928173
TI  - Galanin: analysis of its coexpression in gonadotropin-releasing hormone and
      growth hormone-releasing hormone neurons.
AB  - Galanin is coexpressed in a subset of gonadotropin-releasing hormone (GnRH) and
      growth hormone-releasing hormone (GHRH) neurons in the brain and has an important
      role in the neuroendocrine regulation of gonadotropin and growth hormone
      secretion. Our overall goal has been to understand the functional significance of
      galanin as a cotransmitter with GnRH and GHRH in the regulation of these
      important physiologic processes. To this end, we studied the regulation of
      galanin's expression in GnRH and GHRH neurons under a variety of physiologic and
      experimental conditions. Using double-label in situ hybridization and
      computerized image analysis, we observed that in GnRH neurons, galanin's
      expression is increased over the course of development in both sexes. Galanin
      achieves a higher basal expression in GnRH neurons in females, and it is sexually
      differentiated in the adult as a result of the differential exposure to
      testosterone during the neonatal critical period. Galanin is induced in GnRH
      neurons coincident with and subsequent to the proestrous luteinizing hormone
      surge (reflecting the combined action of estradiol and progesterone) acting
      indirectly on GnRH neurons through a synaptic relay. Galanin's expression in GnRH
      neurons is inhibited during lactation, when the neuroendocrine reproductive axis
      is relatively quiescent. In GHRH neurons, the expression of galanin is also
      induced over the course of development in both sexes. Galanin's expression in
      GHRH neurons in the adult is sexually differentiated, but in this case, its
      expression is higher in males than females, reflecting the stimulatory effect of
      testosterone on galanin in the male. Galanin's expression in GHRH neurons is
      induced by growth hormone (GH), whereas the absence of GH leads to a reduction of
      galanin mRNA in these same cells. On the basis of these observations, we conclude
      that galanin is an important target for regulation by many hormones, and we
      postulate that as a cotransmitter, galanin acts presynaptically to modulate the
      secretion of GnRH and GHRH, possibly by altering their pulsatile release
      patterns, which in turn influences the release of the gonadotropins and GH from
      the pituitary.

PMID- 9928174
TI  - Neuroendocrine interactions between galanin, opioids, and neuropeptide Y in the
      control of reproduction and appetite.
AB  - Galanin is a pleiotropic neuroendocrine signal produced in discrete
      subpopulations of neurons distributed in several sites in the hypothalamus.
      Neuropeptide Y and beta-endorphin also display pleiotropism, but they are
      produced by subpopulations of neurons located only in the arcuate nucleus of the
      hypothalamus. Each of these neuropeptides exerts a regulatory influence on
      reproduction and appetitive behavior. Experimental and morphologic evidence from
      our laboratory show direct contacts and interplay among these diverse signals.
      Seemingly, an interconnected network composed of these three neuropeptide
      producing neurons provides precision and site specificity in the relay of
      information necessary to govern reproduction and appetite. Disruptions in this
      interplay are likely to manifest in untoward consequences such as infertility and
      obesity.

PMID- 9928175
TI  - Galanin-galanin receptor systems in the hypothalamic paraventricular and
      supraoptic nuclei. Some recent findings and future challenges.
AB  - Galanin and galanin receptors are widely distributed within the central nervous
      system, but historically much research has been focused on hypothalamic galanin
      systems including those in the preoptic area, paraventricular nucleus (PVN),
      supraoptic nucleus (SON), and median eminence. In early studies, galanin mRNA,
      immunoreactivity, and binding sites were detected in neurons of the SON and both
      the magnocellular and parvocellular regions of the PVN, all of which also contain
      vasopressin, oxytocin, and several other peptides. This article briefly reviews
      some important recent studies of the electrophysiologic effects of galanin on
      magno-cellular neurons in vitro; regulation of galanin expression by the
      physiologic stimulus of lactation; the role of parvocellular galanin systems in
      energy balance, body weight, and obesity; and the regional and cellular
      localization of galanin and galanin receptor mRNAs in the PVN/SON. In relation to
      the latter issue, two distinct galanin receptor subtypes, GalR1 and GalR2, have
      now been cloned and characterized. In situ hybridization histochemical studies of
      rat brain by several groups have consistently demonstrated GalR1 mRNA in the SON
      and PVN, in the magnocellular and parvocellular regions. By contrast, our recent
      experiments using [35S]-labeled oligonucleotide probes detected GalR2 mRNA
      enriched in the parvocellular, not the magnocellular regions of the PVN, and the
      transcripts were not detected in the SON, whereas studies by other using a
      digoxigenin-labeled RNA probe have detected GalR2 mRNA in the SON (and PVN).
      Nonetheless, given the known effects of hyperosmotic stimuli, changes in
      metabolic status, and various hormones on galanin synthesis and release and the
      ability of galanin to regulate the electrical and secretory activity of
      magnocellular neurons, it will be of interest to determine any possible
      (differential) regulation of galanin receptor subtype expression and the pre- and
      postsynaptic roles of GalR1 and GalR2 receptors in magnocellular and
      parvocellular neurons.

PMID- 9928176
TI  - Galanin in ascending systems. Focus on coexistence with 5-hydroxytryptamine and
      noradrenaline.
AB  - Galanin can be synthesized in several ascending systems including cholinergic
      forebrain neurons, serotonergic dorsal raphe neurons, and the noradrenergic locus
      coeruleus system. Recent immunohistochemical studies suggest that of these three
      systems, the locus coeruleus neurons express the highest levels of galanin and
      that in cortex and hippocampus galanin peptide can only be detected in the
      noradrenergic projections. Electrophysiologic studies show that galanin
      hyperpolarizes both serotonergic dorsal raphe neurons and noradrenergic locus
      coeruleus neurons at fairly high concentrations (10(6)-10(-7) M). In addition,
      galanin at low concentrations (10(-9) M) enhances the 5-HT- and noradrenaline
      induced hyperpolarization. Consequently, a galanin antagonist could attenuate an
      inhibitory tone on both dorsal raphe and locus coeruleus neurons and thus perhaps
      exert antidepressant activity.

PMID- 9928177
TI  - Electrophysiologic effects of galanin on neurons of the central nervous system.
AB  - The neuropeptide galanin is found in a large number of neurons and nerve
      terminals throughout the nervous system. In nerve terminals, galanin is contained
      in large dense-core vesicles and is released upon electrical stimulation. A
      variety of electrophysiologic studies have examined the effects of galanin
      application onto neurons of the central nervous system. Overall, galanin appears
      to have inhibitory effects in the central nervous system, causing in most cases a
      potassium-mediated hyperpolarization accompanied by a decrease in input
      resistance. Other actions include a reduction in presynaptic excitatory inputs
      and an interaction with other applied neurotransmitters. These effects are robust
      and long lasting in most cases. Differences in the responses mediated by the
      various receptor subtypes have not been explored electrophysiologically. More
      complete analysis awaits the availability of more potent and specific receptor
      anatagonists.

PMID- 9928178
TI  - Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin
      fragment/5-hydroxytryptamine1A receptor interactions in the brain.
AB  - The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain
      are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor
      mediated transmission at the postjunctional level, whereas galanin receptor
      activation mimics the inhibitory action of 5-HT1A receptor activation at the soma
      dendritic level, leading to reductions of 5-HT metabolism and release. These
      interactions have been shown in both receptor binding studies and functional
      studies. In view of the present findings, galanin antagonists may represent a new
      type of anti-depressant drug, based on the 5-HT hypothesis of depression, by
      enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover,
      following intracerebroventricular injection galanin was found to be internalized
      in a population of hippocampal nerve cells mainly representing GABA,
      somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these
      findings is discussed in relation to the concept of volume transmission.

PMID- 9928179
TI  - Galanin expression within the basal forebrain in Alzheimer's disease. Comments on
      therapeutic potential.
AB  - The inhibitory neuropeptide galanin has widespread distribution throughout the
      central nervous system. Studies indicate that galanin modulates cognition by
      regulating cholinergic basal forebrain (CBF) neuron function. The chemoanatomic
      organization of galanin within the mammalian CBF differs across species. In
      monkeys, all CBF neurons coexpress galanin, whereas in apes and humans galanin is
      found within a separate population of interneurons that are in close apposition
      to the CBF perikarya. Pharmacologic investigations revealed a low and high
      affinity galanin receptor within the basal forebrain in humans. In vitro
      autoradiographic investigations of the primate brain indicate that galanin
      receptors are concentrated within the anterior subfields of the CBF as well as
      bed nucleus of the stria terminalis, amygdala, and entorhinal cortex.
      Galaninergic fibers hyperinnervate remaining CBF neurons in Alzheimer's disease.
      Because galanin inhibits the release of acetylcholine in the hippocampus, it has
      been suggested that the overexpression of galanin in Alzheimer's disease may
      downregulate the production of acetylcholine within CBF perikarya, further
      exacerbating cholinergic cellular dysfunction in this disorder. These
      observations suggest that the development of a potent galanin antagonist would be
      a useful step towards the successful pharmacologic treatment of Alzheimer's
      disease.

PMID- 9928180
TI  - Galanin inhibits performance on rodent memory tasks.
AB  - Central administration of galanin produces performance deficits on a variety of
      rodent learning and memory tasks. Galanin impairs acquisition and/or retention of
      the Morris water task, delayed nonmatching to position, T-maze delayed
      alternation, starburst radial maze, and passive avoidance in normal rats. A
      primary site of action is the ventral hippocampus, with an additional modulatory
      site in the medial septum-diagonal band. The behavioral actions of galanin at rat
      septohippocampal sites mediating cognitive processes are consistent with previous
      reports of inhibitory actions of galanin on acetylcholine release and
      cholinergically activated transduction at the M1 muscarinic receptor in rat
      hippocampus. The peptidergic galanin receptor antagonist M40 blocks the
      inhibitory actions of galanin on memory tasks. Treatment combinations of M40 with
      an M1 agonist, TZTP, improves performance on delayed nonmatching to position, in
      rats with 192IgG-saporin-induced cholinergic lesions of basal forebrain neurons.
      Nonpeptide, bioavailable, subtype-selective galanin receptor antagonists may
      provide tools to test the hypothesis that antagonism of endogenous galanin, which
      is overexpressed in the basal forebrain in Alzheimer's patients, can contribute
      to the alleviation of the cognitive deficits associated with Alzheimer's disease.

PMID- 9928181
TI  - Regulation of galanin in memory pathways.
AB  - Based on early immunocytochemical findings, galanin (GAL) was postulated to
      function as an inhibitory cotransmitter in rat cholinergic memory pathways.
      However, recent studies indicate that in the basal state GAL is not widely
      expressed by forebrain cholinergic neurons in rats. Inhibition of cholinergic
      transmission by cosecreted GAL may be enhanced under certain conditions, because
      GAL gene expression in the cholinergic basal forebrain is significantly increased
      prior to puberty and following nerve growth factor treatment. Other sources of
      GAL in rat septohippocampus that could interact with cholinergic pathways include
      noradrenergic neurons in the locus ceruleus and vasopressinergic neurons in the
      bed nucleus of the stria terminalis (BST) and medial amygdala (Me). GAL is
      extensively colocalized within these steroid-sensitive cell groups where its
      expression is upregulated by gonadal hormones. GAL, acting via the GALR1 receptor
      subtype, does not appear to directly regulate the activity of cholinergic
      neurons, but it may regulate the release of vasopressin and GAL into
      septohippocampus from BST/Me neurons.

PMID- 9928182
TI  - Modulation of acetylcholine and serotonin transmission by galanin. Relationship
      to spatial and aversive learning.
AB  - This paper presents evidence that galanin is a potent in vivo modulator of basal
      acetylcholine release in the rat brain with qualitatively and quantitatively
      differential effects in the dorsal and ventral hippocampus. Galanin perfused
      through the microdialysis probe decreased basal acetylcholine release in the
      ventral hippocampus, while it enhanced acetylcholine release in the dorsal
      hippocampus. Galanin (3 nmol/rat) infused into the ventral hippocampus impaired
      spatial learning acquisition, while it tended to facilitate acquisition when
      injected into the dorsal hippocampus. These effects appear to be related to
      activation of GAL-R1 (ventral hippocampus) and GAL-R2 (dorsal hippocampus)
      receptors, respectively. However, the effects of galanin on acetylcholine release
      and on spatial learning appear not to be directly related to cholinergic
      mechanisms, but they may also involve interactions with noradrenaline and/or
      glutamate transmission. Galanin administered into the lateral ventricle failed to
      affect acetylcholine release, while this route of administration produced a long
      lasting reduction in 5-HT release in the ventral hippocampus, indicating that
      galanin is a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo.
      Subsequent studies supported this hypothesis, showing that the effects on 5-HT
      release in vivo are most likely mediated by a galanin receptor in the dorsal
      raphe. The implications of these findings are discussed in relation to the role
      of acetylcholine in cognitive functions in the forebrain and the role of the
      raphe 5-HT neurons in affective disorders.

PMID- 9928183
TI  - Galanin: a significant role in depression?
AB  - This paper describes a hypothesis that attempts to account for how changes in
      noradrenergic systems in the brain can affect depression-related behaviors and
      symptoms. It is hypothesized that increased activity of the locus coeruleus (LC)
      neurons, the principal norepinephrine (NE)-containing cells in the brain, causes
      release of galanin (GAL) in the ventral tegmentum (VTA) from LC axon terminals in
      which GAL is colocalized with NE. It is proposed that GAL release in VTA inhibits
      the activity of dopaminergic cell bodies in this region whose axons project to
      forebrain, thereby resulting in two of the principal symptoms seen in depression,
      decreased motor activation and decreased appreciation of pleasurable stimuli
      (anhedonia). The genesis of this hypothesis, which derives from studies using an
      animal model of depression, is described as well as recent data consistent with
      the hypothesis. The formulation proposed suggests that GAL antagonists may be of
      therapeutic benefit in the treatment of depression.

PMID- 9928184
TI  - Galanin in somatosensory function.
AB  - Galanin-like immunoreactivity and galanin receptors are found in dorsal root
      ganglion (DRG) cells and in dorsal horn interneurons, suggesting that this
      neuropeptide may have a role in sensory transmission and modulation at the spinal
      level. Expression of galanin or galanin receptors in the DRG and spinal cord are
      altered, sometimes in a dramatic fashion, by peripheral nerve injury or
      inflammation. Under normal conditions, galanin occurs in a small population of
      primary sensory neurons as well as in spinal interneurons. However, following
      peripheral nerve injury or inflammation, expression of galanin in primary
      afferents and spinal cord is upregulated. We examined the role of galanin in
      spinal processing of nociceptive information under normal and pathologic
      conditions in a large series of electrophysiologic and behavioral studies.
      Results suggest that under normal conditions galanin exerts tonic inhibition of
      nociceptive input to the central nervous system. After peripheral nerve injury
      the inhibitory control exerted by endogenous galanin, probably released from DRG
      neurons, is increased. During inflammation, galanin presumably released from
      dorsal horn interneurons also exerts an inhibitory function. Thus, stable galanin
      agonists may be useful in the treatment of inflammatory and neuropathic pain.

PMID- 9928185
TI  - Galanin expression in neuropathic pain: friend or foe?
AB  - We investigated a possible link between galanin expression and evoked pain
      accompanying painful partial sciatic nerve lesions. Increased galanin
      immunoreactivity (IR) in the dorsal horn, in gracile nucleus, and in sensory
      neurons following chronic constriction injury (CCI) compared to complete sciatic
      transection suggested a facilitatory role in thermal and mechanical
      hypersensitivity (allodynia). We therefore investigated the effects of endogenous
      interleukin-6 (IL-6) and nerve growth factor (NGF) on allodynia and neuropeptide
      expression. IL-6 knockout mice showed decreased allodynia and galanin-IR compared
      to wild-type mice, but also decreased substance P (SP)-IR in the dorsal horn.
      Anti-NGF-treated rats with CCI also showed decreased allodynia and SP-IR, but
      increased galanin-IR in the dorsal horn. These results suggest that evoked pain
      is more tightly linked to SP than to galanin expression. If galanin's effects are
      inhibitory as the bulk of the literature suggests, its effects are subordinate to
      those of SP and to other changes following CCI.

PMID- 9928186
TI  - Regulation of expression of galanin and galanin receptors in dorsal root ganglia
      and spinal cord after axotomy and inflammation.
AB  - Galanin can normally be detected only in a few dorsal root ganglion (DRG)
      neurons, but it is dramatically upregulated after peripheral nerve injury in both
      rat and monkey. Galanin is stored in large dense core vesicles, which after
      axotomy are often found close to the membrane of afferent nerve endings in the
      dorsal horn. In the monkey there is an increase in galanin in many nerve
      terminals in the superficial dorsal horn after axotomy, but such an increase is
      more difficult to detect in the rat. Galanin is also present in local dorsal horn
      neurons, where it is upregulated by peripheral inflammation. Both galanin-R1 and
      galanin-R2 receptor mRNAs are expressed in rat DRGs, mainly in, respectively,
      large and small DRG neurons. Galanin-R1 receptor mRNA is downregulated in DRG
      neurons after axotomy, and a small decrease in galanin-R2 receptor mRNA levels
      can also be seen. After peripheral tissue inflammation galanin-R1 receptor mRNA
      levels decrease and galanin-R2 receptor mRNA levels increase. The present results
      show that galanin and galanin receptors are present in sensory and local dorsal
      horn neurons and are regulated by nerve injury and inflammation. Galanin may
      therefore be involved in processing of pain information, primarily exerting
      analgesic effects. Whereas local dorsal horn neurons represent a defense system
      against inflammatory pain, we have proposed that a second defense system, against
      neuropathic pain, is intrinsic to DRG neurons.

PMID- 9928187
TI  - Syntheses of galanins, their fragments, and analogs.

PMID- 9928188
TI  - Galanin upregulation in glial cells after colchicine injection is dependent on
      thyroid hormone.

PMID- 9928189
TI  - Galanin and NH2-terminal galanin fragments in central cardiovascular regulation.

PMID- 9928191
TI  - Effects of antimetabolites to glucose and fatty acids on galanin-1 receptor mRNA
      levels in the hypothalamic paraventricular and supraoptic nuclei.

PMID- 9928190
TI  - Expression of galanin and the GALR1 galanin receptor subtype in the colon of
      children with paradoxical fecal incontinence.

PMID- 9928193
TI  - Effects of different galanins on the release of acetylcholine in the various
      areas of rat brain.

PMID- 9928194
TI  - Galanin and galanin receptor expression in neuroblastoma.

PMID- 9928196
TI  - Distribution of galanin immunoreactivity in the bronchi of humans with
      tuberculosis.

PMID- 9928192
TI  - Hypothalamic galanin is upregulated during hyperphagia.

PMID- 9928198
TI  - Time-dependent effects of intrahippocampal galanin on spatial learning.
      Relationship to distribution and kinetics.

PMID- 9928195
TI  - Modulation of a 5-HT1A receptor-mediated behavioral response by the neuropeptide
      galanin.

PMID- 9928197
TI  - Galanin-based peptides, galparan and transportan, with receptor-dependent and
      independent activities.

PMID- 9928199
TI  - Effects of three galanin analogs on the outward current evoked by galanin in
      locus coeruleus.

PMID- 9928200
TI  - The immunology of xenotransplantation: introduction.

PMID- 9928201
TI  - The future promises of xenotransplantation.
AB  - The use of animals as a source of organs and tissues for humans has been an
      enduring goal of transplantation. Xenotransplantation, as such, would overcome a
      shortage of human donors and allow for biochemical or genetic approaches to
      modification of transplants. The use of animal organs and tissue, however, is
      hindered by an intense immune response of the recipient against the graft. The
      molecular basis for this immune response has recently been elucidated, at least
      in part, and specific approaches to therapy, including the genetic engineering of
      source animals, have been developed. Other hurdles, including the physiologic
      limitations of the transplant and the possibility of transferring infectious
      agents from the transplant into the host, may also be important. The development
      of specific therapies and the application of genetic engineering to overcome
      these problems can now be envisioned. As the immunologic, physiologic, and
      infectious hurdles to xenotransplantation are addressed, new efforts will focus
      on the use of the transplant to impart novel functions to answer the therapeutic
      needs of the transplant recipient.

PMID- 9928202
TI  - Physiological obstacles after xenotransplantation.
AB  - The incompatibility of allografts is restricted to immunologic factors such as
      the MHC class I and class II antigens. Anatomic, physiological, and biochemical
      characteristics are identical. This is completely different in xenografts. The
      upright position of man is unique in nature. Gravity therefore exerts a different
      impact on the anatomic situation of organs such as lung, heart, liver, and
      kidney. More pronounced are differences on the humoral and enzymatic basis.
      Complex interactions existing in allografts are totally disturbed in xenogeneic
      situations. Up- and downregulation controlled by releasing factors on the one
      hand and inhibitors on the other must be species-specific. These actions of
      mainly proteases are both fast and in most cases depend on species-specific
      receptors. Examples are growth hormones which could stimulate the xenografts to
      unrestricted growth, as in pig hearts in the human patient. Enzymes not
      metabolized by the liver would constantly stimulate mechanisms to a level that is
      not compatible with life, and other reactions could be more expressed in the
      donor species than in man and thus disturb these interactions. Products like
      albumin are carriers for other molecules and need to be compatible for binding
      sites. Pig and human albumin have an amino acid identity of less than 65%
      erythropoetin (EPO) of less than 82%, and complement of less than 70%. All
      factors are obviously without specific function in the future recipient, the
      human patient. In contrast, pig complement would, as a foreign molecule, induce
      the alternative complement pathway in the human recipient, leading to unknown
      side effects. It is not sufficiently investigated whether under such
      physiological and anatomic differences a long-term survival of xenograft or
      recipient is possible--a chain is as strong as its weakest link.

PMID- 9928203
TI  - Genetic engineering in the pig. Gene knockout and alternative techniques.
AB  - Since endothelial cells (EC) are the major target cells during hyperacute
      rejection and are likely in delayed graft rejection, most of the genetic
      engineering of the xenotransplant donor is aimed at modifying their properties.
      Among the various strategies that are reviewed are the genotypic or phenotypic
      knockout of the alpha 1,3Gal antigen, which is a major target of xenoantibodies
      and is also probably involved in innate cellular response. In addition, the
      success of the transgeny of complement regulatory proteins is well established.
      In vitro data from analyses of the mechanisms of endothelial cell activation also
      suggest that other molecules could be used to regulate apoptosis or thrombotic
      microenvironment or to minimize recipient T-cell activation by inhibiting
      costimulatory proteins such as CD40 or B7. Alternative to usual knockout
      techniques (thus far not available in pigs, where no ES cells have been derived)
      will be presented.

PMID- 9928204
TI  - Induction of bilateral transplantation tolerance to cellular and perfused
      allografts and xenografts with donor hematopoietic cells.
AB  - We have recently introduced a new approach for induction of transplantation
      tolerance to donor alloantigens using well-tolerated non-myeloablative
      conditioning across MHC and xenogeneic barriers in mice. Our regimen consists of
      no or very low doses of total lymphoid irradiation (TLI), previously shown to be
      tolerogenic because of profound yet non-myeloablative immunosuppression, followed
      by deletion of donor-reactive host lymphocytes activated in vivo with donor
      hematopoietic cells with a single dose of cyclophosphamide. Recipients of
      immunosuppressive regimen with lower intensity (e.g., no or one single dose of
      TLI) required a larger inoculum of donor bone marrow cells; the reverse was also
      true, both regimens resulting in stable mixed chimerism. A combination of low
      dose TLI followed by depletion of donor-reactive host cells with cyclophosphamide
      resulted in consistent engraftment of even low numbers of T-cell-depleted donor
      derived hematopoietic cells, known to be much more difficult to engraft, with
      consistent induction of permanent and donor-specific transplantation tolerance to
      donor skin allografts with signs of similar success across xenogeneic barriers.

PMID- 9928205
TI  - The risk of infection in xenotransplantation. Introduction.

PMID- 9928206
TI  - Infection and xenotransplantation. Developing strategies to minimize risk.
AB  - Infection in transplantation results from interaction between the level of immune
      suppression and the epidemiologic exposures of the recipient. "Xenosis,"
      infection in xenotransplantation, may be increased beyond that of
      allotransplantation because: (1) the xenograft may serve as a permissive focus of
      infection for donor-derived organisms; (2) these organisms may be unknown or
      xenotropic; (3) microbiologic assays may be unavailable; (4) clinical syndromes
      due to such novel pathogens may not be recognized; (5) the necessary level of
      immune suppression may be greater than for allotransplantation; (6) donor-derived
      organisms may acquire new (e.g., genetic) characteristics in the human host; (7)
      the presence of immune suppression and the high, intrinsic rate of infection may
      mask the presence of xenosis; and (8) MHC-incompatibility may reduce the efficacy
      of the immune response within the xenograft. Because immunocompromised
      individuals are sentinels for infection by many types of novel infectious agents,
      and because there is some unknown level of risk that such pathogens will spread
      to the general population, microbiologic studies must be initiated in tandem with
      preclinical and clinical studies of xenotransplantation.

PMID- 9928207
TI  - Endogenous retroviruses: a potential problem for xenotransplantation?
AB  - To overcome the shortage of suitable human donors for transplantation attention
      has recently turned to the possibility of using genetically modified pigs as a
      source of cells and organs. It has been suggested that such procedures might
      facilitate the introduction of novel retroviruses, normally resident in the pig
      germ line, into the human population (Stoye and Coffin, Nature Medicine 1: 1100,
      1995). The consequences of such a transfer remain unclear; however, the
      demonstration that certain porcine cell lines express infectious retroviruses
      which can infect human cells (Patience et al., Nature Medicine 3: 282-286, 1997)
      emphasizes that there are grounds for practical concern. We have now cloned the
      envelope genes of the expressed viruses and are using these clones in studies of
      the interaction of the porcine viruses with their cellular receptors. We have
      also initiated studies of the inheritance and expression of human-tropic
      endogenous proviruses present in different pig populations. These studies reveal
      that at least two classes of human-tropic endogenous porcine retrovirus are
      widely distributed in pigs (Le Tissier et al., Nature 389: 681-681, 1997). The
      implications of our results for assessing the potential risk of retroviral
      transfer during xenotransplantation are discussed.

PMID- 9928208
TI  - Immunosuppression by retroviruses: implications for xenotransplantation.
AB  - Retroviruses induce in the infected host an immunosuppression the severity of
      which depends on the viral load. A pronounced immunosuppression is induced by
      human and simian immunodeficiency viruses (HIV and SIV) ultimately leading to
      AIDS. It is very likely that HIV originated by trans-species transmission from
      primates. In contrast, SIVs are not pathogenic for their natural hosts probably
      as the result of virus-host coevolution. We have shown that a retroviral protein,
      the transmembrane envelope protein, may play an important role in retrovirus
      induced immunosuppression and that all retroviruses share an evolutionarily
      highly conserved domain in this protein. We demonstrate that synthetic peptides
      corresponding to this domain of different retroviruses, including HIV, the baboon
      endogenous virus (BaEV), and different porcine endogenous retroviruses (PERVs),
      are immunosuppressive. We provide evidence that BaEV and different PERVs,
      including those able to grow in human cells, are immunosuppressive for
      lymphocytes of different species including human. This implies that
      xenotransplantation may result in a trans-species transmission of endogenous
      retroviruses derived from the donor animal. In analogy to HIV and SIV high-titer
      virus replication may cause an AIDS-like disease in the immunosuppressed human
      transplant recipient. Two additional points have to be considered: First, human
      anti-complement proteins produced by transgenic animals will also protect the
      virus and, second, the virus may be transmitted to other humans and thus increase
      its pathogenic potential.

PMID- 9928209
TI  - The risk of using baboons as transplant donors. Exogenous and endogenous viruses.
AB  - African nonhuman primates harbor several exogenous and endogenous retroviruses
      which deserve further consideration in the transplant setting. In particular,
      simian foamy viruses (SFV), simian T-cell lymphotropic virus (STLV), baboon
      endogenous virus (BaEV), and simian endogenous retrovirus (SERV) are all carried
      by baboons and may be transmitted to humans by transplantation. We have found
      baboons to have high seroprevalence rates to both SFV and STLV, and molecular and
      serologic methods have been developed to detect such agents. In addition, current
      nonhuman primate breeding programs have thus far not focused on eliminating these
      viruses. In summary, the close genetic relationship with humans and number of
      persistent viral infections in baboons translates into a much greater infectious
      disease risk when compared to that of other domesticated species.

PMID- 9928210
TI  - Xenozoonoses and the xenotransplant recipient.
AB  - The use of animal cells, tissues, or organs for humans is being investigated as
      an alternative to allotransplantation and as therapy for a broad range of disease
      states including diabetes, Parkinson's disease, and neurologic pain control. The
      risk of transmitting novel infections with these tissues, xenozoonoses, has led
      to much debate. It is well recognized that infections are a hazard with the use
      of all biologic agents. In addition, infections from human donors remain a major
      cause of morbidity and mortality after allotransplantation. Accordingly the
      potential for animal microbial agents to be pathogenic in the human recipient
      after xenotransplantation and be transmissible to others must be critically
      examined. Along with laboratory-based research, clinical trials must be conducted
      in a manner to evaluate the transmission of potential animal infections.
      Pretransplant evaluation should include discussions with the candidate and, if
      possible, with close contacts. Information must be provided as to the potential
      risks of infection and transmission to others. Behavioral modifications which can
      decrease spread of infections should be emphasized. Serial samples should be
      obtained from the patients at defined intervals and if recipients become ill. In
      addition, archiving samples for future evaluation is critical. Prospective
      evaluation will enhance the ability to define and understand the spectrum of
      xenogeneic infections.

PMID- 9928211
TI  - Developing guidelines on the care and use of animals.
AB  - Oversight of laboratory animal care and use in the research environment is
      multilayered. Federal and state regulations apply to many laboratory animal
      species; funding agencies frequently require adherence to additional guidelines;
      institutions may develop in-house policies; and an institution may choose to
      voluntarily participate in an accreditation program, indicating a commitment by
      the institution to apply the most rigorous standards to the animal care and use
      program. In general, regulations follow a prescriptive "engineering" approach,
      while guidelines applied to the care and use of research animals follow a
      "performance" approach, which defines the desired outcome in detail, but
      acknowledges that multiple methods may achieve that outcome. The performance
      approach relies on sound professional judgment, thereby allowing flexibility
      based on an institution's unique circumstances. Further, this approach should
      facilitate the international harmonization of animal care and use standards. The
      performance, or outcome, approach to developing guidelines is described, using
      the Guide for the Care and Use of Laboratory Animals (NRC, 1996) as the model.

PMID- 9928212
TI  - Defining appropriate health status and management programs for specific-pathogen
      free swine for xenotransplantation.
AB  - Swine are expected to be utilized as xenograft donors for both whole-organ and
      cellular transplantation. In order to meet the criteria for regulatory
      guidelines, donor animals are going to have to be free of potential zoonoses and
      other complicating diseases. Screening of animals will have to include tests for
      viruses, bacteria, parasites, congenital defects, and other inapparent diseases
      such as neoplasia or metabolic dysfunctions. The term Specific-Pathogen-Free
      (SPF) swine is a proprietary designation in the U.S. that does not include
      screening for all appropriate organisms for xenotransplantation. A program for
      breeding animals as xenograft donors will have to be conducted in a biomedical
      research facility rather than a conventional farm setting. The research programs
      at such a facility should include serology, microbiology, necropsy, histology and
      parasitology. The use of sentinel animal monitoring in a research facility is one
      method to ensure compliance. It will be impossible to provide complete individual
      animal screening in a timely fashion prior to performing a xenograft transplant.
      Quality control measures need to ensure that there is a reasonable confidence
      that the donor tissue is appropriate for the procedure to be performed. It is
      suggested that a term such as xenograft-defined flora be used to designate the
      appropriate health status of donor animals rather than SPF in order to avoid
      confusion with existing standards.

PMID- 9928213
TI  - Definition of a production specification for xenotransplantation. A European
      perspective.
AB  - In the absence of regulatory guidance on animal production for
      xenotransplantation and the need to conform to European, U.K. and international
      standards of animal health and welfare, Imutran set up a forum of experts in 1994
      to assess the risks associated with the possible transmission of diseases from
      pig to man after transplantation of porcine tissue. This risk assessment set the
      specification for Qualified Pathogen-Free pig production and the animal testing
      required to demonstrate that the specification has been achieved. The invasive
      sampling required for detailed health monitoring of individual source animals is
      in conflict with the aim of producing healthy, normal animals that are not
      subject to undue stress, and produces predominantly retrospective data on a
      donor. Imutran has developed a sampling regime that qualifies age-class cohorts
      and the whole herd by the routine testing of representative sentinel animals.
      Imutran set up a pilot production unit in 1995 and this unit has remained
      populated beyond a 30-month period and has received in excess of 20 cohorts of
      animals by hysterectomy re-derivation. Rigorous testing of sentinels and
      noninvasive testing of individuals have demonstrated that this pilot unit has
      achieved the required specification on a routine basis in a system that has been
      designed to meet European ethical and animal welfare concerns, within the
      constraints of the strict U.K. animal research laws and an ISO 9001 quality
      environment.

PMID- 9928214
TI  - Public oversight and economics: introduction.

PMID- 9928215
TI  - International issues in transplantation. Setting the scene and flagging the most
      urgent and controversial issues.
AB  - Organ transplantation is the primary technique for treatment of end-stage organ
      failure and has benefited more than one million persons world wide. A number of
      patients have survived for well over 25 years and survival rates at 5 years can
      be 70% or higher for many organ transplant programs. However, currently more than
      40,000 patients are waiting for a kidney, and in western Europe mortality rates
      for patients waiting for a heart, liver, or lung range from 15 to 30%. The
      potential need for transplants is even greater and this imbalance between supply
      and demand creates technical and ethical problems including the risk of organ
      trafficking. Consequently the number of available organs must be increased. In
      some cases the organ shortage reflects a true lack of donors, but more often it
      results from the failure to turn potential into actual donors. The transplant
      commission of the Council of Europe has just approved a document recommending
      that member states ensure that all potential donors are identified and as many as
      possible converted to actual donors. Even with the highest organ donation rate,
      the indications for organ and tissue transplantation will continue to increase,
      perpetuating the gap between supply and demand. Organ transplantation, whether
      living or cadaveric, might be supplemented or replaced by the use of artificial
      organs, although problems such as power supply, thrombosis, infection, and
      biocompatibility pose obstacles to long-term function. The use of animals as an
      alternative source is considered, but so many problems still remain unresolved
      that xenotransplantation cannot be put forth as a solution at this time. This
      paper reviews these issues and, citing the Spanish experience, offers strategies
      to improve the organ donation rate.

PMID- 9928216
TI  - Public versus private approaches to organ procurement and transplantation.

PMID- 9928217
TI  - Current issues in Japan.

PMID- 9928218
TI  - The research-policy continuum. Comparing allo- and xenotransplantation.
AB  - Where are we on the continuum leading from research to policy decisions in allo-
      and xenotransplantation? In the case of allotransplantation all the activities
      needed in achieving an effective research policy transfer are ongoing. Research
      is vibrant and several technology assessment reports have been produced and
      translated into decisions at the policy, institutional, and practice levels, and
      quality monitoring activities are an integral part of transplant programs. The
      field of xenotransplantation is young and so the major emphasis in
      xenotransplantation will remain knowledge production for the coming years.
      Exploring the intricacies of the physiology of xenotransplantation, the
      associated risks of infection, and the complexity of the immunological response
      will remain research priorities. The social and ethical debate, necessary to the
      formulation of sound health policy, will intensify and be focused on whether to
      allow human experimentation and under what conditions.

PMID- 9928220
TI  - The Draft U.S. Public Health Service Guideline on Infectious Disease Issues in
      Xenotransplantation. The DHHS Interagency Working Group on Xenotransplantation.

PMID- 9928219
TI  - The Swiss Technology Assessment project on xenotransplantation.
AB  - The Swiss Technology Assessment (TA) project on xenotransplantation is intended
      to study the opportunities and risks of this technique, recognizing the input of
      those involved in and those affected by it. This also implies taking into account
      the clinicoscientific, social, ethical, economic, and legal aspects. The
      situation in Switzerland is analyzed in depth, with reference to the acceptance,
      ethics, and existing federal legislation pertinent to xenotransplantation. Apart
      from consultation with experts from various specialized areas, a written
      questionnaire was sent to more than 100 organizations, institutions, companies,
      and individuals. The resulting assessments range from clear approval to complete
      rejection of the notion of xenotransplantation. Even acceptance was granted only
      on condition that criteria such as security (minimum risk of infection) and
      respect for human dignity and animal protection issues are respected. Such
      criteria are generally accepted, but if concrete conclusions must be drawn, we
      must recognize that opinions vary in today's discussions on ethics in
      Switzerland. It is commonly agreed that animals are not objects, but their
      precise status is not clear. Moreover, there are no patented ethical "recipes"
      for handling risks.

PMID- 9928221
TI  - Public confidence and government regulation.

PMID- 9928222
TI  - Xenotransplantation: perspectives from The Netherlands.
AB  - Recently, the Health Council of the Netherlands published a report on
      xenotransplantation. The technique is considered ethically acceptable, both from
      a human and from an animal point of view. Clinical application should not yet be
      permitted, however, because of continuing rejection problems and growing concerns
      on safety aspects associated with possible transfer of pathogens from the
      xenotransplant to the host. More research is necessary. Mainly because of the
      risk for infection, nonhuman primates are not considered acceptable as source
      animals; the genetically engineered pig is at present the source animal of
      choice. Legally, import in the Netherlands of (organs from) source animals from
      within Europe is difficult to prevent. Therefore experiments with such material
      are not subjected to licensing by the government, which is the case for
      experiments involving genetic engineering with animals in the Netherlands, but
      only by local review boards. This situation is considered unwanted and adjustment
      of the pertinent law is suggested. Also, both genetically engineered animals and
      patients carrying organs from such animals fall under the European Genetically
      Modified Organisms regulations. These regulations are not designed for this case
      and conflicts may arise. Agreements on how to handle this situation have to be
      made at the European level. It is proposed to draft a national law on
      "biologicals," medical products consisting at least partly of living materials.
      Pending such regulations, it is suggested, also on a European level, that
      xenotransplants be considered as medicines, which would allow adequate control of
      safety aspects.

PMID- 9928223
TI  - Experience of gene therapy in the United Kingdom.
AB  - The UK Committee on the Ethics of Gene Therapy recommended the establishment of a
      supervisory body with collective expertise, experience, and authority to regulate
      gene therapy. In November 1993, the supervisory body, known as the Gene Therapy
      Advisory Committee (GTAC), was established. It interacts with other bodies,
      including the Medicines Control Agency, local research ethics committees, the
      Health and Safety Executive, and the Hospital Trust. When proposals for gene
      therapy are reviewed, there is careful assessment of the scientific merits, the
      competence of those undertaking the research, and the risks involved. Each
      proposal is assessed by several independent expert advisors, in specific aspects
      of the research. The researchers are apprised of the issues raised by the
      assessors and given the opportunity to modify their proposals. The research team
      is then given the opportunity to make a brief presentation to the GTAC. The
      proposals may be approved subject to conditions, deferred until further issues
      are resolved, or rejected on the basis that the proposal is unethical or the
      science unsound. Researchers are expected to provide the committee with regular
      progress reports. This paper discusses the experience of gene regulation in the
      United Kingdom.

PMID- 9928224
TI  - Researcher-driven versus policy-driven economic appraisal. The case of
      xenotransplantation.
AB  - Worldwide ethical considerations have led to banning markets for human organs and
      to promoting supply of organs for transplantation strictly on a donor
      noncommercial basis. In most industrialized countries, including France, there is
      a shortage of organs available for transplantation. Following on the earlier
      debate between Titmuss and Arrow over banning the market for blood supply, this
      presentation first challenges the conventional economic view that the ban is
      necessarily responsible for these critical shortages. It will argue that it is
      the obstacles to adequate exhortation (i.e., the efforts to inform and persuade
      participants in the donor system who cannot be paid for what they supply) rather
      than the inefficiency per se of appeals to donor altruism that are the cause of a
      shortage. The paper will then discuss the way a market for non-human organs may
      be an efficient alternative to a donor system by supplying a substitute good.
      Data from a survey in a random sample of the French general population (> or = 18
      years of age in June 1997; response rate = 62.0%; n = 1,011) show that less than
      half of the respondents (42.4%) agreed that xenotransplantations should be
      developed. Support for xenotransplantation was higher (50.6% vs. 38.2% in the
      rest of the sample, p < 0.001) among respondents who declare that in case of an
      accidental death of a family member, they would accept the use of his organs for
      transplantation, among those with the highest level of knowledge about
      transplantation (48.6% vs. 39.4%, p < 0.005), and among blood donors (45.9% vs.
      38.3%, p < 0.02). Supply of non-human organs should remain under the control of
      the public sector in order to be consonant with current donor systems for human
      organs. Recommendations for adequate regulation of the R&D process of non-human
      alternatives for organ transplantations will be made.

PMID- 9928225
TI  - International issues and public perception: introduction.

PMID- 9928226
TI  - Monitoring infectious diseases.

PMID- 9928228
TI  - The need for international sharing and reporting in xenotransplantation.

PMID- 9928227
TI  - Current developments on xenotransplantation in the Council of Europe.

PMID- 9928229
TI  - Development of databases and registries. International issues.
AB  - This paper describes the U.S. Public Health Service (PHS) efforts to develop a
      National Xenotransplantation Registry (NXR). The function of the registry is
      discussed, paying particular attention to data collection and harmonization
      issues. The need for standardization and coordination on an international scale
      is presented and the benefits of such efforts are discussed. Finally, a
      recommendation for an international effort aimed at harmonization is made.

PMID- 9928230
TI  - Analysis of factors for the prediction of the response to xenotransplantation.
AB  - Predicting the response to xenotransplantation is difficult, but can be based
      upon (i) past clinical experience, (ii) opinion surveys and focus groups, (iii)
      predictable variables, and (iv) the allotransplant experience. Baby Fae, the
      Pittsburgh baboon liver transplants, and the Jeff Getty baboon marrow transplant
      have taught us (a) not to underestimate hurdles, (b) to communicate
      professionally, (c) not to promise too much, (d) that lobbying can be effective,
      (e) that "being the first" is important, and (f) that the media can be fickle.
      The Swedish islet cell and the U.S. neural tissue transplants suggest that
      patients without immediately life-threatening illnesses will accept xenogeneic
      tissue and that the public/media will not respond negatively when there is little
      fanfare. Limited opinion surveys/focus groups suggest a degree of
      reluctance/revulsion that is more common in women, minorities, and the less
      educated, and when the likely donor is a subhuman primate. Predictable positive
      public-response variables include perceptions of (a) adequacy of the scientific
      base, (b) adherence to globally agreed upon guidelines, (c) legitimacy/competence
      of regulatory bodies, and (d) adequate infectious risk assessment and management.
      A likely negative predictor is the role of animal rights activists (more in
      Europe, less in the U.S. and the developing world). Less predictable is the
      response of the media and what other societal concerns dominate the news at the
      time. Cultural concerns will need careful study. Allotransplant experience
      suggests that informed religious opinion can be accommodating a new technology.
      Psychological factors will be important and will need professional management.

PMID- 9928231
TI  - Transplantation and xenotransplantation. Legal perspectives for Third World
      countries.

PMID- 9928232
TI  - Xenotransplantation and its implications. Background information for the press.

PMID- 9928233
TI  - 5-HT4 receptors: gene, transduction and effects on olfactory memory.
AB  - In this paper we discuss 1) the primary structures, pharmacology, and brain
      distribution of cloned 5-HT4 receptors; 2) the chromosomal localization of the h5
      HT4 receptor; 3) whether benzamides are full or partial agonists because of a
      species or a coupling difference; 4) the intrinsic activity of 5-HT4 receptors
      and inverse agonism of GR125487 in COS-7 cells but not in colliculi neurons; 5)
      the modulation of 5-HT4 receptor binding and activity; and 6) the long-term
      blockade of K+ channels by 5-HT4 agonists and its effect on olfactory memory. We
      conclude that 1) the cloning of 5-HT4 receptors in different species using RT-PCR
      from different tissues reveals the presence of several splice variants for 5-HT4
      receptors differing in the C-terminal part, downstream from the amino acid L358;
      2) the pharmacological properties of 5-HT4 receptors are dependent on the
      cellular context in which they are expressed; and 3) 5-HT4 agonists can be added
      to the list of compounds having pro-cognitive properties.

PMID- 9928234
TI  - Serotonin receptor variants in disease: new therapeutic opportunities?
AB  - This review describes a novel genetic approach to the assessment of receptor
      function that is based on association studies of polymorphisms within human
      genes. The realization that variations within human genes may significantly
      affect gene function has led to increased use of this approach in recent years.
      Analysis of polymorphisms within the human 5-HT2A receptor is used as a specific
      example of the application of association genetics to elucidate gene function.
      The interaction of many neuroleptics and antidepressants with 5-HT2A receptors
      points up the potential importance of this receptor for understanding and
      treating neuropsychiatric disorders such as schizophrenia and depression.

PMID- 9928235
TI  - Genetic variation in human 5-HT receptors: potential pathogenetic and
      pharmacological role.
AB  - Mutation screening identified variants of h5-HT1A (Gly-22-Ser, Ile-28-Val, Arg
      219-Leu), h5-HT1B (Phe-124-Cys), h5-HT2A (Thr-25-Asn, His-452-Tyr), h5-HT2C (Cys
      23-Ser) and h5-HT7 (Thr-92-Lys, Pro-279-Leu) receptors. Screening of h5-HT1D, h5
      ht1e, h5-ht1f and h5-ht5 receptor genes failed to detect any significant
      mutations. No differences in radioligand binding properties were observed between
      the h5-HT1A Ile-28-Val variant receptor (VR) and the wildtype receptor (WTR).
      Binding profiles of the h5-HT1A Gly-22-Val variant and the WTR were also very
      similar, but the 8-OH-DPAT-induced down-regulation and desensitization of the VR
      was attenuated. The h5-HT1B Phe-124-Cys variant leads to considerable changes in
      [3H]5-carboxamidotryptamine binding: Bmax was decreased and the affinity of
      various h5-HT1B ligands was modified (usually increased; e.g., in the case of
      sumatriptan). The h5-HT2A His-452-Tyr variant causes an alteration of the
      amplitude and timing of intracellular calcium mobilization in platelets from 452
      His/452-Tyr heterozygous compared to 452-His/452-His homozygous individuals.
      Most, but not all, of the VRs listed above were examined for association with,
      e.g., bipolar depression and schizophrenia, yet no relation was observed. The
      most consistent finding was an association between a silent mutation (102T/C) in
      the h5-HT2A receptor gene and schizophrenia; this association may be explained by
      linkage disequilibrium with a functional variant in the regulatory region of the
      gene. Studies of the therapeutic response to clozapine produced no homogeneous
      results with respect to the pharmacogenetic significance of the various mutations
      in the h5-HT2A and h5-HT2C receptor genes.

PMID- 9928236
TI  - Gs protein-coupled serotonin receptors: receptor isoforms and functional
      differences.
AB  - Three distinct mammalian Gs coupled serotonin receptor genes have been
      identified, 5-HT4, 5-ht6, and 5-HT7, which produce at least seven different
      functional receptors through alternative splicing. One of the chief questions
      facing workers in this area mirrors that confronting the serotonin receptor field
      as a whole: why so many subtypes? The answer to this question is made more
      elusive at present by two further considerations. First, there may well be
      additional Gs coupled receptor subtypes yet to be described. Secondly, although
      the various isoforms of 5-HT4 and 5-HT7 have been shown to be functional in in
      vitro assays, it remains to be shown that all isoforms have biological
      significance. This paper will summarize some of the differences at the molecular
      and cellular level that are becoming apparent among the 5-HT4, 5-ht6 and 5-HT7
      receptor subtypes and their various isoforms. As an example, it will focus on the
      5-HT7 system, and describe recent developments in ascribing particular functions
      to differences due to alternative splicing.

PMID- 9928237
TI  - Identification and characterization of RNA editing events within the 5-HT2C
      receptor.
AB  - RNA editing is a post-transcriptional modification that generates an RNA
      transcript with a nucleotide sequence different from its gene. We have recently
      discovered RNA editing events, involving the conversion of adenosine bases to
      inosine residues, within the RNA encoding the serotonin 2C (5-HT2C) receptor.
      Editing events at four major positions, termed A, B, C and D, as well as one
      minor site termed C', are predicted to alter amino acids within the second
      intracellular loop of the G-protein coupled 5-HT2C receptor. Editing is mediated
      by at least two members of a family of adenosine deaminases and is contingent
      upon the presence of an extensive RNA duplex structure formed by exonic and
      intronic sequences of 5-HT2C receptor precursor messenger RNA (pre-mRNA). This
      critical secondary structure has been observed within brain pre-mRNA derived from
      four species; the isolation of edited 5-HT2C receptor transcripts from these
      samples further confirms the evolutionary conservation of this RNA processing
      event. Among members of the 5-HT2 receptor family, editing within second
      intracellular loop RNA is unique to the 5-HT2C receptor. Editing within the 5
      HT2C receptor generates receptor isoforms that differ in their ability to
      interact with the phospholipase C signaling cascade in a transfected cell line,
      suggesting that this RNA processing event may contribute to the modulation of
      serotonergic neurotransmission in the central nervous system.

PMID- 9928238
TI  - 5-HT4 receptors: cloning and expression of new splice variants.
AB  - On the basis of differences in the potencies and intrinsic activity of 5-HT4
      receptor agonists in different biological models it has been suggested that there
      is heterogeneity among 5-HT4 receptors. Here, we report the molecular cloning of
      several 5-HT4 receptor splice variants in mouse, rat, and human brain. Our data
      suggest that the differences in efficacy of 5-HT4 ligands on 5-HT4 receptor
      mediated responses in several tissues is due to differences in coupling
      efficiency rather than to the presence of different 5-HT4 receptor isoforms.

PMID- 9928239
TI  - Inducible knockout strategies to probe the functions of 5-HT receptors.
AB  - Gene targeting has proven to be extremely powerful in various fields of
      biological research. Through this technique, knockout mice lacking a particular
      gene and thus a particular protein, can be generated. One limitation to this
      technique is the fact that mice develop without the protein of interest and
      therefore, developmental compensations may have taken place, contributing to an
      observed phenotype. Inducible strategies, those which allow the timing of
      expression of a gene to be regulated, are currently being developed and should
      prove useful when applied to gene targeting technology. In order to begin to
      apply such new technologies to the field of gene targeting, we first created and
      tested several reporter constructions using the tetracycline inducible system.
      Here we describe the creation of several beta-galactosidase reporter
      constructions and the results of in vitro testing in Cos-7 cells. We then discuss
      future knockout strategies based upon our observations.

PMID- 9928240
TI  - Mouse 5-HT2B receptor-mediated serotonin trophic functions.
AB  - 5-HT2B receptors, in addition to phospholipase C stimulation, are able to trigger
      activation of the proto-oncogene product p21ras. During mouse embryogenesis, a
      peak of 5-HT2B receptor expression is detected at the neurulation stage; we
      localized the 5-HT2B expression in neural crest cells, heart myocardium, and
      somites. The requirement for functional 5-HT2B receptors shortly after
      gastrulation, is supported by culture of embryos exposed to 5-HT2B-high affinity
      antagonist such as ritanserin, which induces morphological defects in the
      cephalic region, heart and neural tube. Functional 5-HT2B receptors are also
      expressed during the serotonergic differentiation of the mouse F9 teratocarcinoma
      derived clonal cell line 1C11. Upon 2 days of induction by cAMP, 5-HT2B receptors
      become functional, and on day 4, the appearance of 5-HT2A receptors coincides
      with the onset of active serotonin transporter by these cells. Active serotonin
      uptake is modulated by serotonin suggesting autoreceptor functions for 5-HT2B
      receptors.

PMID- 9928241
TI  - Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice.
AB  - Serotonin 5-HT2C receptor null mutant mice were generated to assess the
      contribution of this receptor to the actions of serotonin. Mutant mice displayed
      both an epilepsy and obesity phenotype. The epilepsy syndrome was characterized
      by spontaneous seizures, lowered seizure threshold, enhanced seizure propagation
      and sound-induced seizure susceptibility. These findings implicate 5-HT2C
      receptors in the regulation of neuronal network excitability. It was also
      observed that body weight and adipose tissue deposition were elevated in adult
      mutant mice relative to their wild type littermates. Paired-feeding studies
      suggest that the obesity syndrome is a result of increased food intake. In
      addition, mutants displayed reduced sensitivity to the appetite suppressant
      actions of non-specific serotonergic agonists. These studies establish a role for
      5-HT2C receptors in the serotonergic regulation of body weight and food intake.

PMID- 9928242
TI  - 5-HT1B receptor modulation of prepulse inhibition: recent findings in wild-type
      and 5-HT1B knockout mice.
AB  - Sensorimotor gating of the startle reflex occurs when the presentation of a weak
      "prepulse" 30-500 msec prior to a startling stimulus inhibits the reflex, and is
      called prepulse inhibition (PPI). The study of PPI has recently been extended to
      mice to take advantage of recent advances in molecular genetics, because several
      neuropsychiatric disorders including schizophrenia, obsessive compulsive
      disorder, and schizotypal personality disorder are characterized by PPI deficits.
      Studies in wild-type and 5-HT1B knockout mice suggest that activation of 5-HT1B
      receptors decreases PPI. The direct 5-HT1A/1B agonist RU24969 decreases PPI in
      wild-type but not 5-HT1B knockout mice. Likewise, the serotonin releasing
      compounds MDMA(+), MBDB(+/-), and alpha-ethyltryptamine (AET) have no effect on
      PPI in wild-type mice, but increase PPI in 5-HT1B knockout mice. As the direct 5
      HT1A agonist 8-OH-DPAT increases PPI in mice, the unmasking of these effects may
      also contribute to the PPI-increasing effects of 5-HT releasers in 5-HT1B
      knockout mice.

PMID- 9928244
TI  - The putative 5-ht6 receptor: localization and function.
AB  - Until recently, the majority of actions of the neurotransmitter 5
      hydroxytryptamine (5-HT) were generally believed to be mediated by members of the
      5-HT1, 5-HT2, 5-HT3 and 5-HT4 receptor families. The application of molecular
      cloning techniques has revealed the existence of gene products encoding several
      novel, putative 5-HT receptors for which little or no prior pharmacological or
      functional data presently exist. The present challenge to pharmacologists is to
      determine the physiological relevance of these gene products, establish whether
      or not they function as endogenous receptors, find selective agents and determine
      potential therapeutic uses of these compounds. Here we review work detailing the
      cloning and characterization of the recombinant 5-ht6 receptor, its distribution
      and evidence for functional responses mediated by naturally occurring 5-ht6
      receptors.

PMID- 9928243
TI  - Putative 5-ht5 receptors: localization in the mouse CNS and lack of effect in the
      inhibition of dural protein extravasation.
AB  - Putative 5-ht5 receptor binding sites were visualized by in vitro autoradiography
      using [125I]LSD (in the presence of clozapine and spiperone) or [3H]5
      carboxamidotryptamine (in the presence 8-OH-DPAT, GR127935 and spiperone). Under
      these conditions, no [3H]5-carboxamidotryptamine labeling was detected in the
      brain of mice lacking the gene encoding the putative 5-ht5a receptor (knockout
      mice), whereas intermediate densities of binding sites were seen in the olfactory
      bulb and neocortex of wild-type mice. [125I]LSD labeled the same areas as [3H]5
      carboxamidotryptamine in wild-type mice. High densities of [125I]LSD binding
      sites were observed in the medial habenula of wild type and knockout mice. 5-CT
      competed for [125I]LSD binding sites with an affinity of 2 nM in the olfactory
      bulb and neocortex of wild-type mice and an affinity of 30 nM in the habenula of
      knockout mice, suggesting that habenular labeling might be accounted for by
      putative 5-ht5b receptors. In the presence of 5'-guanylylimidodiphosphate, 5-CT
      displaced [125I]LSD from putative 5-ht5a and 5-ht5b sites with a 6-times and 3
      times lower affinity, respectively, suggesting that both receptor subtypes are
      coupled to G proteins in brain. We also studied the inhibitory effect of 5-CT on
      dural neurogenic inflammation in knockout mice. In wild type mice, 3 ng/kg 5-CT
      inhibited dural protein extravasation by 60%. A similar effect was observed in
      knockout mice, even in the presence of the 5-HT1B receptor antagonist GR127935.
      These results suggest that the inhibitory effects of 5-CT are not mediated by a
      site with the characteristics of the putative 5-ht5 receptor.

PMID- 9928245
TI  - A three-state receptor model: predictions of multiple agonist pharmacology for
      the same receptor type.
AB  - Recent studies have demonstrated that activation of the same G-protein coupled
      receptor can generate different agonist pharmacology depending on the signaling
      pathway(s) to which it couples. Two types of behavior have been exemplified;
      differences in affinity order, and differences in efficacy order with the same
      affinity order. The two-state model of receptor activation cannot explain these
      data, since a single active receptor state cannot couple differently to the two
      response pathways for different ligands. We have therefore extended the two-state
      model to a three-state model in which receptors exist in three states: an
      inactive state, R, and two different active states, R* and R**. The model has two
      modes, the 'intact mode', in which all the equilibria are linked; and the
      'isolated mode' in which the two response pathways are isolated from each other,
      giving effectively two separate two-state systems. In the 'intact mode' the same
      agonist affinity order is predicted for both response pathways, but a different
      efficacy order. In the 'isolated mode', since the equilibria are no longer
      linked, the model predicts that a different affinity order may be obtained for
      the two pathways. Owing to the linkage of all the equilibria in the intact three
      state model the level of constitutive activity through one pathway can affect the
      direction of agonism through the other pathway, resulting in the conversion of an
      inverse agonist into a positive agonist. This change in the direction of agonism
      is also predicted to occur when the two response pathways are isolated. The three
      state model therefore predicts that agonists, acting at the same receptor, may
      show different affinity orders and different efficacy orders depending upon which
      response is measured and the assay system used, and also predicts that inverse
      agonism may be system dependent.

PMID- 9928246
TI  - Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists.
AB  - There is now considerable evidence that a single receptor subtype can couple to
      multiple effector pathways within a cell. Recently, Kenakin proposed a new
      concept, termed "agonist-directed trafficking of receptor stimulus", that
      suggests that agonists may be able to selectively activate a subset of multiple
      signaling pathways coupled to a single receptor subtype. 5-HT2A and 5-HT2C
      receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP)
      accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies
      of agonists (referenced to 5-HT) differed depending upon whether IP accumulation
      or AA release was measured. For the 5-HT2C receptor system, some agonists (e.g.
      TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD)
      favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways.
      For the 5-HT2A receptor system, all agonists tested had greater relative efficacy
      for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different
      for 5-HT2A agonists when sequential effects in a pathway were measured (IP
      accumulation vs. calcium mobilization). These data strongly support the agonist
      directed trafficking hypothesis.

PMID- 9928247
TI  - Interactions between effectors linked to serotonin receptors.
AB  - In general, there are two types of interactions between effector signaling
      pathways. "Homologous" interactions are those that occur within a receptor system
      to alter its own responsiveness, for example the loss of responsiveness
      (desensitization) that can occur upon agonist occupancy of a receptor.
      "Heterologous" interactions are those that occur between different receptor
      systems where the responsiveness of one receptor system is regulated (positively
      or negatively) by activation of another receptor system (i.e., "cross-talk").
      Many, if not all receptors, couple to multiple cellular effector pathways and
      alterations in the responsiveness of a receptor system can be effector pathway
      dependent which underscores the importance of studying each effector coupled to a
      receptor. Regulation of receptor system responsiveness, and consequently the
      efficacy of drugs, is a highly dynamic process. Perhaps by exploiting these
      interactions, new targets for pharmacotherapy may be uncovered which will provide
      for increased efficacy and specificity of drug action.

PMID- 9928248
TI  - Serotonergic antagonist effects on trafficking of serotonin 5-HT2A receptors in
      vitro and in vivo.
AB  - The mechanism by which antagonists down-regulate 5-HT2A receptors in unknown. We
      here report that a variety of 5-HT2A antagonists induce a change in the
      subcellular distribution of 5-HT2A receptors both in vitro and in vivo. In a
      stably transfected NIH 3T3 cell-line, brief exposure to 1 muM clozapine caused a
      2.5-fold increase in intracellular 5-HT2A-like immunoreactivity, as measured by
      confocal microscopy. Confirmatory studies utilizing a biotin-trap technique,
      demonstrated that the increase in intracellular immunoreactivity results from
      internalization of receptor from the cell surface. Exposure of transfected cells
      to other 5-HT2A receptor antagonists produced similar increases in intracellular
      5-HT2A-like immunoreactivity. In vivo administration of clozapine (20 mg/kg, sc,
      X 7 days) caused a greater than twofold increase in intracellular
      immunoreactivity in cell bodies of cortical pyramidal neurons. Additionally,
      chronic clozapine administration was associated with decrease in labeling of
      apical dendrites on pyramidal cells. These results show that clozapine causes a
      change in subcellular distribution of 5-HT2A receptors in vitro and in vivo.

PMID- 9928249
TI  - Regulation of levels of 5-HT2A receptor mRNA.
AB  - We have been able to identify two separate pathways present in P11 cells that can
      increase the levels and stability of 5-HT2A receptor mRNA. One pathway is
      activated following exposure of cells to serotonin and is dependent upon
      activation of a PKC isoform that is susceptible to downregulation by a 24-h
      pretreatment with PMA; another pathway is activated following treatment of cells
      with a calcium ionophore. This pathway is not dependent on activation of PKC
      isoforms that can be downregulated by a 24-h treatment with phorbol ester. Such
      heterologous regulation of levels of 5-HT2A receptor mRNA may be important in
      understanding in vivo events where multiple factors contribute to the modulation
      of levels of cell surface receptors.

PMID- 9928250
TI  - Creation of a constitutively activated state of the 5-HT2A receptor by site
      directed mutagenesis: revelation of inverse agonist activity of antagonists.
AB  - Constitutively active GPCR have revealed novel properties of drugs that exhibit
      classical competitive antagonism at the native forms of GPCR. These drugs reverse
      basal levels of constitutive activity, indicating that they have inverse agonist
      activity. We were interested in determining if competitive antagonists of the
      native 5-HT2A receptor, in particular, antipsychotic drugs, exhibit inverse
      agonist activity at the constitutively active 5-HT2A receptor. All of the drugs
      tested reduced basal IP production of constitutively active 5-HT2A receptors,
      indicating that they all exhibited inverse agonist activity. Risperidone and
      ketanserin produced the greatest inhibition of basal IP production resulting in a
      reduction of basal activity in the C322K mutant receptor of 82% and 80%,
      respectively. Antipsychotic drugs display inverse agonist activity, indicating
      that stabilization of the inactive conformation of the 5-HT2A receptor may be a
      key component of their mechanism of action.

PMID- 9928251
TI  - Pharmacological characterization of the constitutively activated state of the
      serotonin 5-HT2C receptor.
AB  - Previous studies from our laboratory have shown that the 5-HT2C serotonin
      receptor can be rendered constitutively active by changing amino acid 312 (third
      intracellular loop) from serine to lysine (S312K). In the present study, detailed
      radioligand binding analyses were performed to characterize the constitutively
      activated state of S312K mutant receptors. All agonists tested displayed high
      affinity for both [3H]5-HT and [3H]mesulergine binding to S312K receptors, but
      displayed low affinity for [3H]mesulergine binding to native 5-HT2C receptors.
      [3H]5-HT labeled the same total number of S312K binding sites as [3H]mesulergine.
      5-HT2C antagonists inhibited S312K basal inositol phosphate production. These
      results suggest that S312K receptors mimic the active conformation of native 5
      HT2C receptors and provide a good model system for evaluating drugs for inverse
      agonist activity. Also, S312K receptors may represent a new system for screening
      5-HT2C agonist activity by comparing [3H]mesulergine binding to native and S312K
      mutant receptors.

PMID- 9928252
TI  - A putative alpha-helical G beta gamma-coupling domain in the second intracellular
      loop of the 5-HT1A receptor.
AB  - We have identified a conserved threonine residue in the second intracellular (i2)
      loop of the 5-HT1A receptor that when mutated to alanine prevents coupling to G
      beta gamma-mediated signaling, while preserving G alpha i-induced actions. In
      this review, we investigate the characteristics and potential role of the i2
      domain in the coupling of the 5-HT1A receptor and other receptors to G proteins.
      The i2 domain, as well as portions of the i3 domain, is predicted to form an
      amphipathic alpha-helix with a positively charged face and a hydrophobic face.
      Mutagenesis experiments support a model in which the hydrophobic faces of these
      alpha-helical domains form an intracellular binding "pocket" for interaction with
      G proteins. Embedded in the hydrophobic face, Thr 149 is crucial for signaling
      through G beta gamma subunits, perhaps via interaction with its hydroxyl side
      chain. Mutation of other residues of the i2 domain of Gi-coupled receptors is
      required to substantiate the importance of the alpha-helical i2 domain in
      receptor-G beta gamma signaling. If confirmed in other receptors, these results
      support a general model in which activated receptor and G beta gamma subunits
      remain associated to interact with effectors in a receptor-specific manner.

PMID- 9928253
TI  - Activation of the mitogen-activated protein kinase pathway via the 5-HT2A
      receptor.
AB  - The mitogen-activated protein kinase (MAPK) pathway, classically associated with
      cell growth and dependent on tyrosine kinases such as MAPK kinase (MEK), can
      modulate smooth muscle contractility, and our laboratory has tested the
      hypothesis that 5-HT can activate the MAPK pathway in arterial smooth muscle
      through activation of a 5-HT2A receptor. Tyrosine kinase inhibitors including
      genistein and the specific MEK inhibitor PD098059, but not the inactive tyrosine
      kinase congener daidzein reduced and shifted 5-HT-induced contraction rightward
      in isolated, endothelium-denuded rat arteries. Activation of a tyrosine
      kinase/MEK via the 5-HT2A receptor was partially independent of two major
      signaling pathways typically associated with the 5-HT2A receptor--activation of L
      type voltage gated calcium channels and phospholipase C. Western analyses using
      antibodies directed against tyrosyl-phosphorylated-, activated Erk MAPK, and MEK
      proteins from cultured aortic smooth muscle cells demonstrated that 5-HT
      activated MEK and the Erk MAPKs in a time-, concentration-, receptor- and
      tyrosine kinase-dependent manner. Taken together, these findings provide evidence
      for a novel pathway of vascular signal transduction--activation of the MAPK
      pathway--for the 5-HT2A receptor.

PMID- 9928254
TI  - Serotonin 5-HT2A receptor activation inhibits cytokine-stimulated inducible
      nitric oxide synthase in C6 glioma cells.
AB  - C6-glioma cells endogenously express both 5-HT2A receptors and inducible nitric
      oxide synthase (iNOS). iNOS can be induced by transcriptional activation to
      produce nitric oxide (NO) in response to a challenge with the pro-inflammatory
      cytokines TNF-alpha and IFN-gamma. Experiments were conducted to determine
      whether 5-HT2A receptor activation could modify the production of NO in response
      to the inducing agents. 1 muM DOI produced a dose-dependent inhibition of the
      cytokine-inducted nitrite levels of 40% which was inhibited by spiperone and
      ritanserin. In addition, the DOI-mediated decrease was prevented by the PKC
      inhibitor chelerythrine (100 nM). The effectiveness of DOI was lost when added
      more than two hours after the addition of inducing agent, suggesting that DOI was
      regulating iNOS at the level of transcription rather than post-translationally.
      We suggest that there is a link between the serotonergic system and NO-mediated
      immune responses in the brain.

PMID- 9928255
TI  - Molecular, cellular and physiological characteristics of 5-HT-moduline, a novel
      endogenous modulator of 5-HT1B receptor subtype.
AB  - The serotonergic transmission is considered as a neuromodulatory system in the
      Central Nervous System. 5-HT1B receptors play an important role in this
      modulatory activity. We have purified from mammalian brain an endogenous peptide,
      LSAL, we called 5-HT-moduline, interacting specifically with 5-HT1B receptors.
      This interaction is characterized by a high affinity (Ki = 10(-10) M) and a non
      competitive mechanism. Direct [3H]5-HT-moduline binding revealed a single
      population of sites having an apparent affinity constant close to 10(-10) M.
      Autoradiographic studies showed a brain distribution of [3H]5-HT-moduline binding
      sites closely related to the 5-HT1B receptors. In functional studies, the peptide
      is able to reverse the activity of a 5-HT1B agonist in the nanomolar range.
      Furthermore, this antagonist effect is also observed in vivo on mice behavior.
      Immunocytochemistry revealed an heterogeneous distribution of 5-HT-moduline in
      mouse brain. The labeled structures correspond to cellular profiles with axon
      like prolongations. Moreover, in vitro, LSAL is released in a Ca++, K(+)
      dependent manner. Therefore, 5-HT-moduline behaves as a neurotransmitter. The
      fact that 5-HT-moduline induces the desensitization of 5-HT1B receptors reflects
      the existence of a novel and efficient mechanism able to rapidly modulate the
      serotonergic activity.

PMID- 9928256
TI  - Oleamide-induced modulation of 5-hydroxytryptamine receptor-mediated signaling.
AB  - We investigated the effects of oleamide, a fatty acid amide isolated from the
      cerebrospinal fluid of sleep-deprived cats, on serotonin receptor-mediated
      signaling in cultured mammalian cells. Oleamide demonstrated opposing effects on
      5-HT2A and 5-HT7 receptors, in rat pituitary cells and transfected HeLa cells,
      respectively. Oleamide caused a potentiation of 5-HT-elicited inositol phosphate
      formation mediated by the 5-HT2A receptor, but inhibited the effects of 5-HT on
      cAMP production mediated by the 5-HT7 receptor. In addition, oleamide alone
      caused a significant increase in cAMP accumulation that was dependent on the
      presence of the 5-HT7 receptor, but was not blocked by clozapine. These results
      demonstrate that oleamide can have diverse effects on 5-HT-mediated signal
      transduction at different subtypes of mammalian 5-HT receptors. Additionally, our
      data suggest that oleamide may act at an allosteric site on the 5-HT7 receptor
      and can elicit functional responses via activation of this site.

PMID- 9928257
TI  - Regulation of membrane excitability in the central nervous system by serotonin
      receptor subtypes.
AB  - Serotonin exerts multiple electrophysiological effects on neurons of the central
      nervous system. It is now known that this diversity reflects at least in part the
      existence of multiple serotonin receptor subtypes. An example of this occurs in
      the CA1 region of the hippocampus where as many as ten different serotonin
      receptor subtypes appear to be expressed. Recent electrophysiological studies
      have been able to assign specific functional roles to at least 5 of these
      receptors. These receptors are differentially expressed in the two different cell
      types present in this region, pyramidal cells and GABAergic interneurons, and
      mediate different effects on membrane excitability. This distribution is
      consistent with the different functional roles played by these cells in
      hippocampus. Thus the differential expression of serotonin receptor subtypes in
      the CA1 region allows serotonin to modify the function of hippocampal neuronal
      networks in a manner that is both selective and precise.

PMID- 9928258
TI  - Role of somatodendritic 5-HT autoreceptors in modulating 5-HT neurotransmission.
AB  - A very important element controlling serotonin (5-HT) release throughout the
      brain is the 5-HT1A autoreceptor present on the soma and dendrites of 5-HT
      neurons since it exerts a negative feedback influence on their firing activity.
      This 5-HT1A autoreceptor receives an increased activation by endogenous 5-HT at
      the beginning of a treatment with a selective 5-HT reuptake inhibitor (SSRI) and,
      consequently, a decreased 5-HT neuronal firing activity is obtained. As the SSRI
      treatment is prolonged, the 5-HT1A autoreceptor desensitizes and firing activity
      is restored in the presence of the SSRI. That this adaptive change underlies, at
      least in part, the delayed therapeutic effect of SSRI in major depression is
      supported by the acceleration of the antidepressant response by the concomitant
      administration of the 5-HT1A autoreceptor antagonist pindolol with SSRIs.

PMID- 9928259
TI  - Serotonin transporter function in vivo: assessment by chronoamperometry.
AB  - Local application of selective serotonin reuptake inhibitors, fluvoxamine and
      citalopram, prolonged the clearance of exogenously administered serotonin (5-HT)
      in both the dentate gyrus and CA3 region of the dorsal hippocampus, as measured
      using in vivo chronoamperometry. These effects were abolished in rats pretreated
      with 5,7-dihydroxytryptamine. The NE uptake inhibitors, desipramine and
      protriptyline, did not alter the 5-HT signal in the CA3 region, but prolonged the
      clearance of 5-HT in the dentate gyrus; this effect was absent in rats pretreated
      with 6-hydroxydopamine. From these data, it is inferred that both the SERT and
      NET contribute to the active clearance of exogenously applied 5-HT in the dentate
      gyrus. In another experiment, cyanopindolol, an antagonist of the serotonin
      terminal autoreceptor, also prolonged the clearance of 5-HT from the CA3 region.
      These and other data have generated a working hypothesis that activation of the
      terminal serotonin autoreceptor enhances the kinetics of 5-HT uptake through an
      effect on the serotonin transporter.

PMID- 9928260
TI  - Impact of the human genome project on the principles for classification and
      nomenclature of 5-HT receptors.

PMID- 9928261
TI  - Functional chemical neuroanatomy of serotonergic neurons and their targets:
      antibody production and immunohistochemistry (IHC) for 5-HT, its precursor (5
      HTP) and metabolite (5-HIAA), biosynthetic enzyme (TPH), transporter (SERT), and
      three receptors (5-HT2A, 5-ht5a, 5-HT7).

PMID- 9928262
TI  - Molecular cloning of alternatively spliced human 5-HT3 receptor cDNAs.

PMID- 9928264
TI  - Preferential expression of 5-HT1D over 5-HT1B receptors during murine embryonic
      development.

PMID- 9928263
TI  - Efficient expression of neurotransmitter receptors in mammalian cells: use of
      inducible expression systems.

PMID- 9928265
TI  - Characterization of 5-HT- and ionomycin-stimulated changes in levels of
      intracellular calcium and PI hydrolysis in P11 cells.

PMID- 9928266
TI  - Residues in transmembrane regions III and VI contribute to the 5-ht6 receptor
      ligand binding site.

PMID- 9928267
TI  - Central distribution and function of 5-ht6 receptor subtype in the rat brain.

PMID- 9928268
TI  - Distribution of 5-HT2c and 5-ht5a receptor mRNA in human brain.

PMID- 9928269
TI  - 5-HT2B receptors are expressed by neuronal precursors in the enteric nervous
      system of fetal mice and promote neuronal differentiation.

PMID- 9928270
TI  - The 5-HT2B receptor controls the overall 5-HT transport system in the 1C11
      serotonergic cell line.

PMID- 9928271
TI  - Signaling pathways and targets of the 5-HT2B receptor in the 1C11 serotonergic
      cell line.

PMID- 9928272
TI  - Functional properties of 5-HT-moduline in the immune system: a model for central
      nervous system investigation.

PMID- 9928273
TI  - Operational studies of synergistic interactions with 5-HT1B/1D receptors.

PMID- 9928274
TI  - Calcium influx through voltage-gated calcium channels regulates 5-HT3 receptor
      channel desensitization in NG108-15 cells.

PMID- 9928275
TI  - Is there a functional response-overlap between 5-HT3 and nicotinic ion channel
      receptors?

PMID- 9928277
TI  - Characterization of the "silent" 5-HT1B receptors of rabbit iliac artery.

PMID- 9928276
TI  - Pharmacological characterization of the "silent" 5-HT1B-like receptors of rabbit
      ear artery.

PMID- 9928278
TI  - 5-HT receptors in rat jugular vein: information from RT-PCR and operational
      studies.

PMID- 9928279
TI  - Autoradiographic characterization, anatomical distribution, and developmental
      pattern of a new 5-HT site in human brain.

PMID- 9928280
TI  - Parallel evaluation of 5-HT1A receptor localization and functionality:
      autoradiographic studies with [35S]-GTP gamma S and the novel, selective
      radioligand, [3H]-S 15535.

PMID- 9928281
TI  - In vitro visualization of 5-HT receptors in rat brain using [35S]GTP gamma S
      binding.

PMID- 9928282
TI  - [3H]5-HT binding to cloned human, dog, and rat 5-HT1D and 5-HT1B receptors.

PMID- 9928283
TI  - High affinity of SDZ HTF-919 related molecules for calf and human caudate 5-HT4
      receptors.

PMID- 9928284
TI  - Absorption and brain penetration of a high affinity, highly selective 5-HT2C
      receptor antagonist, RS-102221.

PMID- 9928285
TI  - The selective 5-HT1B receptor inverse agonist SB-224289, potently blocks terminal
      5-HT autoreceptor function both in vitro and in vivo.

PMID- 9928286
TI  - Consequences of 5-HT re-uptake blockade on postsynaptic 5-HT1A receptor
      activation: an electrophysiological and neurochemical study in guinea pig dorsal
      raphe and hippocampus.

PMID- 9928287
TI  - 5-HT1A agonist activity of pindolol: reversal of the inhibitory effects on cell
      firing in the dorsal raphe nucleus but not in the hippocampus by WAY-100,635.

PMID- 9928288
TI  - Comparison of native 5-HT3 receptors purified from various neuroblastoma-derived
      cell lines and bovine brain with recombinant 5-HT3-AL receptors purified after
      expression in HEK293 cells.

PMID- 9928289
TI  - Inhibition by propofol of 5-HT3 receptors in excised patches of NIE-115 cells.

PMID- 9928290
TI  - Agonist and antagonist binding to rabbit cortical 5-HT2A receptors: opposite
      effects of magnesium.

PMID- 9928291
TI  - Pharmacological profile of the prejunctional 5-HT1 receptors mediating inhibition
      of sympathetic vasopressor outflow in the pithed rat.

PMID- 9928292
TI  - Evidence for the putative 5-HT7 receptor mediating direct relaxation to 5
      hydroxytryptamine in canine cerebral blood vessels.

PMID- 9928293
TI  - Effects of acute and chronic treatment with clozapine on dopamine release in rat
      nucleus accumbens slice preparations.

PMID- 9928295
TI  - Post-synaptic 5-HT1A and 5-HT2A receptors are increased in Parkinson's disease
      neocortex.

PMID- 9928294
TI  - Involvement of 5-HT1A receptors in the consolidation of learning in cognitively
      impaired rats.

PMID- 9928296
TI  - Discrepancies between the in vitro and in vivo 5-HT and norepinephrine re-uptake
      blocking properties of venlafaxine.

PMID- 9928297
TI  - Methiothepin but not methysergide antagonizes TRH effects at the dorsal vagal
      complex.

PMID- 9928298
TI  - Vertebrate locomotion--a lamprey perspective.
AB  - The forebrain, brain stem, and spinal cord contribution to the control of
      locomotion is reviewed in this chapter. The lamprey is used as an experimental
      model because it allows a detailed cellular analysis of the neuronal network
      underlying locomotion. The focus is on cellular mechanisms that are important for
      the pattern generation, as well as different types of pre- and postsynaptic
      modulation. Neuropeptides target different cellular and synaptic mechanisms and
      cause long-lasting changes (> 24 h) in network function.

PMID- 9928299
TI  - Central circuits controlling locomotion in young frog tadpoles.
AB  - The young Xenopus tadpole is a very simple vertebrate that can swim. We have
      examined its behavior and neuroanatomy, and used immobilized tadpoles to study
      the initiation, production, coordination, and termination of the swimming motor
      pattern. We will outline the sensory pathways that control swimming behavior and
      the mainly spinal circuits that produce the underlying motor output. Our recent
      work has analyzed the glycinergic, glutamatergic, cholinergic, and electrotonic
      synaptic input to spinal neurons during swimming. This has led us to study the
      nonlinear summation of excitatory synaptic inputs to small neurons. We then
      analyzed the different components of excitation during swimming to ask which
      components control frequency, and to map the longitudinal distribution of the
      components along the spinal cord. The central axonal projection patterns of
      spinal interneurons and motoneurons have been defined in order to try to account
      for the longitudinal distribution of synaptic drive during swimming.

PMID- 9928300
TI  - Basic principles for generating motor output in the stomatogastric ganglion.
AB  - The lobster stomatogastric ganglion contains 30 neurons and when modulated can
      produce two distinct rhythmic motor patterns--the gastric mill and the pyloric.
      The complete neural circuitry underlying both patterns is well known. Without
      modulatory input no patterns are produced, and the neurons fire tonically or are
      silent. When neuromodulators are released into the ganglion from specific neurons
      or are delivered as hormones, the properties of the neurons and synapses change
      dramatically and modulator-specific gastric mill and pyloric patterns are
      produced. In general the rhythmicity derives from the induced burstiness of the
      neurons, and the pattern from the strengths of the electrical and chemical
      synapses. The organized activity can be traced to a marked reduction of chaotic
      activity in individual neurons when they shift from the unmodulated to the
      modulated state.

PMID- 9928301
TI  - Analysis of the central pattern generator for swimming in the mollusk Clione.
AB  - The pteropod mollusk Clione limacina swims by rhythmic movements of two wings.
      The central pattern generator (CPG) for swimming, located in the pedal ganglia,
      is formed by three groups of interneurons. The interneurons of the groups 7 and 8
      are of crucial importance for rhythm generation. They are endogenous oscillators
      capable of generating rhythmic activity with a range of frequencies typical of
      swimming after extraction from the ganglia. This endogenous rhythmic activity is
      enhanced by serotonin. The interneurons 7 and 8 produce one prolonged action
      potential (about 100 ms in duration) per cycle. Prolonged action potentials
      contribute to determining the duration of the cycle phases. The interneurons of
      two groups inhibit one another determining their reciprocal activity. The
      putative transmitters of groups 7 and 8 interneurons are glutamate and
      acetylcholine, respectively. Transition from one phase to the other is
      facilitated by the plateau interneurons of group 12 that contribute to
      termination of one phase and to initiation of the next phase. Maintaining the
      rhythm generation and transition from one phase to the other is also promoted by
      postinhibitory rebound. The redundant organization of the swimming generator
      guarantees the high reliability of its operation. Generation of the swimming
      output persisted after the inhibitory input from interneurons 8 to 7 had been
      blocked by atropine. Activity of the swimming generator is controlled by a set of
      command neurons that activate, inhibit or modulate the operation of the swimming
      CPG in relation to a behaviorally relevant context.

PMID- 9928302
TI  - How do we approach the locomotor network in the mammalian spinal cord?
AB  - For a large number of vertebrate species it is now indisputable that spinal
      networks have the capability of generating the basic locomotor rhythm. However,
      because of technical difficulties, the rate of progress in defining the intrinsic
      properties of mammalian locomotor rhythm generators has been slow in comparison
      to that made in the study of such networks in lower vertebrates. Investigations
      on afferent and descending control of locomotor activity in mammals have
      demonstrated that many of these pathways interact with the rhythm generator. In
      this review we discuss how these interactions (resetting) can be used for
      outlining relevant spinal circuits as a basis for a future identification of
      individual neurons of the spinal locomotor networks. In this overview we have
      given particular emphasis to selected afferent systems to illustrate the
      possibilities and problems with this approach.

PMID- 9928303
TI  - Initiation of locomotion in mammals.
AB  - Several "locomotor regions" of the mammalian brain stem can be stimulated, either
      electrically or chemically, to induce locomotion. Active cells labeled with c-fos
      within the mesencephalic locomotor region (MLR) have been found in the
      periaqueductal gray, the cuneiform nucleus, the pedunculopontine nucleus, and the
      locus coeruleus. Different subsets of these nuclei appear to be activated during
      locomotion produced in different behavioral contexts. The locomotor nuclei can be
      classified into areas associated with exploratory, appetitive, and defensive
      locomotion, in accordance with the proposal of Sinnamon (1993, Prog. Neurobiol.
      41: 323-344). The interpretation of lesion studies designed to reveal areas of
      the brain essential for locomotion must be based on knowledge of the nuclei which
      become active in the specific locomotor task being tested. An argument is put
      forward in favor of the continued use of the term "mesencephalic locomotor
      region."

PMID- 9928304
TI  - Cerebellar-induced locomotion: reticulospinal control of spinal rhythm generating
      mechanism in cats.
AB  - In a decerebrate cat (locomotor preparation), stimulation of a restricted region
      along the midline cerebellar white matter has been found to evoke generalized
      augmentation of postural muscle tone on a stationary surface (Asanome et al.
      1998. Neurosci. Res. 30: 257-269) and "controlled" locomotion on the surface of a
      moving treadmill. Characteristics of cerebellar-evoked locomotion were similar to
      those of mesencephalic locomotor region-evoked "controlled" locomotion on the
      same animal. Microinjection of a neural tracer (CTb-HRP) into the lesioned
      stimulus site of the cerebellar white matter resulted in both retrograde
      labelling of cells in the fastigial nuclei, bilaterally, and anterograde labeling
      of fibers descending to the brain stem. These results indicated that the
      effective cerebellar stimulus site (cerebellar locomotor region) corresponded to
      the midline region of the hook bundle of Russell (Rasmussen, A. T., 1933. J.
      Comp. Neurol. 57: 165-197), through which crossed fastigioreticular,
      fastigiovestibular, and fastigiospinal fibers pass. In this study, contribution
      of reticulospinal systems to the control of cerebellar-evoked locomotion was
      extensively studied. By stimulating the cerebellar locomotor region and the MLR
      in the same animal, a majority of antidromically identified pontomedullary
      reticulospinal cells were synaptically activated. The results of the present
      study demonstrated that fastigial cells with crossed fastigioreticular fibers and
      reticulospinal fibers play a crucial role in the control of posture and
      locomotion in the locomotor preparation.

PMID- 9928305
TI  - Modulation of information forwarded to feline cerebellum by monoamines.
AB  - The reported results demonstrate that monoamines modulate activity of three
      populations of spinocerebellar tract neurons that are rhythmically active during
      locomotion. However, information on dynamic changes in muscle length and tension
      (signaled by muscle spindle primary afferents and tendon organs) and on the
      absolute length of muscles (signaled by muscle spindle secondary afferents) is
      differently modulated. The transfer of the former is facilitated but that of the
      latter is either facilitated or depressed; it is facilitated via Clarke's column
      dorsal spinocerebellar tract neurons and depressed via dorsal horn dorsal
      spinocerebellar tract neurons. The effects of noradrenaline and serotonin are
      similar.

PMID- 9928306
TI  - Distribution of central pattern generators for rhythmic motor outputs in the
      spinal cord of limbed vertebrates.
AB  - Neuronal networks in the spinal cord are capable of producing rhythmic movements,
      such as walking and swimming, when the spinal cord itself is isolated from the
      brain and sensory inputs. These spinal networks, also called central pattern
      generators or CPGs, serve as relatively simple model systems for our
      understanding of brain functions. In this paper we concentrate on spinal CPGs in
      limbed vertebrates and in particular address the question: Where in the spinal
      cord, in the longitudinal and transverse planes, are they located? We will review
      the use of lesions to isolate the rhythm and pattern-generating parts of the CPG
      network, indirect methods like activity-dependent labeling with [14C]-2
      deoxyglucose, c-fos, sulforhodamine 101, and WGA-HRP, which label presumed
      rhythmically active neurons en bloc, and direct methods such as calcium-imaging,
      extracellular and intracellular recordings, which identify rhythmically active
      cells directly. With this review we hope to highlight the scientific
      disagreements and the consensus, which have emerged from these studies with
      regard to the distribution of the CPG networks in the spinal cord.

PMID- 9928307
TI  - Mechanisms of spontaneous activity in the developing spinal cord and their
      relevance to locomotion.
AB  - The isolated lumbosacral cord of the chick embryo generates spontaneous episodes
      of rhythmic activity. Muscle nerve recordings show that the discharge of
      sartorius (flexor) and femorotibialis (extensor) motoneurons alternates even
      though the motoneurons are depolarized simultaneously during each cycle. The
      alternation occurs because sartorius motoneuron firing is shunted or voltage
      clamped by its synaptic drive at the time of peak femorotibialis discharge.
      Ablation experiments have identified a region dorsomedial to the lateral motor
      column that may be required for the alternation of sartorius and femorotibialis
      motoneurons. This region overlaps the location of interneurons activated by
      ventral root stimulation. Wholecell recordings from interneurons receiving short
      latency ventral root input indicate that they fire at an appropriate time to
      contribute to the cyclical pause in firing of sartorius motoneurons. Spontaneous
      activity was modeled by the interaction of three variables: network activity and
      two activity-dependent forms of network depression. A "slow" depression which
      regulates the occurrence of episodes and a "fast" depression that controls
      cycling during an episode. The model successfully predicts several aspects of
      spinal network behavior including spontaneous rhythmic activity and the recovery
      of network activity following blockade of excitatory synaptic transmission.

PMID- 9928308
TI  - Spinal motor patterns in the turtle.
AB  - Rhythmic alternation between ipsilateral hip flexors and extensors occurs during
      the normal pattern of fictive rostral scratching in response to unilateral
      midbody stimulation in D3-end turtles (complete spinal transection posterior to
      the forelimb enlargement). Unilateral midbody stimulation evokes rhythmic bursts
      of ipsilateral hip flexor activity with no hip extensor activity in D3-end
      turtles with D6-D7 contralateral hemisection (transverse hemisection anterior to
      the hindlimb enlargement). Bilateral midbody stimulation in these turtles evokes
      reconstruction of rhythmic alternation between intact side hip flexors and
      extensors. These normal motor patterns in response to two-site stimulation are
      reconstructed because one-site stimulation in this preparation activates only hip
      flexor rhythms (J. Neurosci. 18: 467). Hip flexor rhythms can therefore occur
      without hip extensor activation. This supports the concept that reciprocal
      inhibition between flexor and extensor interneurons is not required for flexor
      motor rhythm generation. Reciprocal inhibition, when present, also contributes to
      rhythmicity (J. Neurophysiol. 78: 3479; see also Currie and Gonsalves, this
      volume). Both mechanisms for rhythmicity are included in the Grillner unit burst
      generator model: hip flexor unit burst generators may be rhythmogenic in the
      absence of hip extensor activity and reciprocal inhibition contributes to
      rhythmogenesis. Contralateral midbody stimulation assisted in the activation of
      ipsilateral hip extensor rhythmicity during reconstructed rostral scratching.
      This result provides additional support for the hypothesis that a bilateral
      shared core of hip interneuronal circuitry plays a critical role in the
      generation of the normal pattern of fictive rostral scratching (J. Neurosci. 15:
      4343).

PMID- 9928309
TI  - Distributed effects of dopamine modulation in the crustacean pyloric network.
AB  - It is now clear that neuromodulators can reconfigure a single motor network to
      allow the generation of a family of related movements. Using dopamine modulation
      of the 14-neuron pyloric network from the crustacean stomatogastric ganglion as
      an example, we describe two major mechanisms by which network output is
      modulated. First, the baseline electrophysiological properties of the network
      neurons can be altered. Dopamine can affect the activity of each neuron
      independently. For example, DA modulates IA in nearly every neuron in the pyloric
      network, but in opposite directions in different cells. Furthermore, DA usually
      modulates combinations of ionic currents. In some cases, currents with opposing
      actions on cell excitability are simultaneously affected, and the net response
      reflects the sum of these opposing effects. Second, neuromodulators can alter the
      strength of synaptic interactions within the network, quantitatively "rewiring"
      the network. Every synapse in the network is affected by DA, with some increased
      and others decreased in strength. DA acts both pre- and postsynaptically to
      affect transmission: these actions are frequently opposing in sign, and the net
      response arises as the sum of these opposing actions. Finally, spike-evoked and
      graded transmission at the same synapse can be oppositely affected by DA. These
      results emphasize the distributed nature of modulation in motor networks.

PMID- 9928311
TI  - Neuromodulation intrinsic to the central pattern generator for escape swimming in
      Tritonia.
AB  - Extrinsic neuromodulatory inputs to central pattern generators (CPGs) can alter
      the properties and synaptic interactions of neurons in those circuits and thereby
      modify the output of the CPG. Recent work in a number of systems has now
      demonstrated that neurons intrinsic to CPG can also evoke neuromodulatory actions
      on other members of the CPG. Such "intrinsic neuromodulation" plays a role in
      controlling the CPG underlying the escape swim response of the nudibrach mollusc,
      Tritonia diomedea. The dorsal swim interneurons (DSIs) are a bilaterally
      represented set of three serotonergic neurons that participate in the generation
      of the rhythmic swim motor program. Serotonin released from these CPG neurons
      functions both as a fast neurotransmitter and as a slower neuromodulator. In its
      modulatory role, serotonin enhances the release of neurotransmitter from another
      CPG neuron, C2, and also increases C2 excitability by decreasing spike frequency
      adaptation. These neuromodulatory actions intrinsic to the CPG may be important
      for the initial self-configuration of the system into a function CPG and for
      experience-dependent changes in the output such as behavioral sensitization and
      habituation.

PMID- 9928310
TI  - GABAergic control of spinal locomotor networks in the neonatal rat.
AB  - We studied the GABAergic control of the spinal locomotor network using an
      isolated brain stem/spinal cord from newborn rats, in which locomotor-like
      activity was recorded. We demonstrate that endogenously released GABA controls
      the locomotor network, by decreasing or completely abolishing all locomotor-like
      activity. At first, we investigated the role played by GABA in the control of the
      locomotor period. By separately superfusing various compartments of the lumbar
      cord, we identified the targets of GABA. When bath-applied on the upper lumbar
      segments (L1/L2), GABA or its agonists (muscimol, baclofen) modulated the
      locomotor period, whereas it had no effects when bath-applied on the caudal
      lumbar cord (L3/L6). In the second step we studied how GABA may presynaptically
      control the locomotor drive arising from the locomotor network located in L1/L2.
      By use of the partitioned spinal cord, intracellular recordings from the caudal
      pool motoneurons (L4/L5) were performed, while initiating locomotor-like activity
      in L1/L2. We found that GABA or its agonists decreased the monosynaptic locomotor
      drive that the motoneurons received from the L1/L2 network, and we found a
      presynaptic effect exerted through the activation of GABAB receptors. In
      conclusion, this study emphasizes the role played by GABA at various levels in
      the control of the locomotor network in mammals.

PMID- 9928312
TI  - NMDA receptor-mediated oscillatory properties: potential role in rhythm
      generation in the mammalian spinal cord.
AB  - Previous studies have demonstrated that (1) NMDA receptor activation occurs
      during locomotor network operation in lower and higher vertebrates and (2) NMDA
      induces active membrane properties that can be expressed as intrinsic voltage
      fluctuations in cells located in the spinal cord of lower vertebrates, as well as
      in neurons located in supraspinal regions of the mammalian nervous system. This
      paper reviews recent data showing that NMDA can induce similar inherent membrane
      potential behavior in synaptically isolated motoneurons and interneurons in the
      mammalian (in vitro neonatal rat) spinal cord. These TTX-resistant voltage
      fluctuations include rhythmic oscillations and plateau potentials, as well as low
      frequency long-lasting voltage shifts (LLVSs). 5-HT facilitates the
      transformation of LLVSs into oscillatory events, and 5-HT receptor antagonists
      have the reverse effect. In the absence of TTX, locomotor-related rhythmic drive
      potentials in spinal cord neurons can display nonlinear voltage behavior
      compatible with NMDA receptor activation, although other voltage-activated
      conductances are not excluded. Suppression of the nonlinear voltage response
      associated with NMDA receptor activation, via removal of Mg2+, disrupts locomotor
      patterns of network activity. The potential role of NMDA receptor activation in
      the operation of mammalian locomotor networks is discussed in the context of
      these recent observations.

PMID- 9928313
TI  - Enhancement and resetting of locomotor activity by muscle afferents.
AB  - The generation of the normal motor pattern for walking in mammals requires
      feedback from muscle proprioceptors. Two characteristics of the motor pattern
      particularly dependent on proprioceptive signals are (1) the magnitude of
      activity in knee and ankle extensor muscles and (2) the duration of extensor
      bursts during stance. Sensory regulation of these characteristics ensures that
      the level of activity in extensor muscles during stance is appropriate for the
      load carried by the leg and that the swing phase is not initiated when a leg is
      loaded. Many different groups of afferents from flexor and extensor muscles can
      influence the locomotor pattern. Most attention has focused on the action of
      group I afferents from ankle extensors. Electrical stimulation of these afferents
      during extension increases the duration and the magnitude of extensor activity.
      The prolongation of extensor activity depends in part on excitation of the
      extensor half-center by group Ib afferents from Golgi tendon organs. The
      enhancement of the magnitude of extensor bursts is produced primarily via
      disynaptic and polysynaptic pathways opened only during locomotion. The
      involvement of the proprioceptive signals in the generation of locomotor activity
      means that the gains in reflex pathways must be constantly calibrated according
      to the biomechanical properties of the locomotor system. Alteration of these
      properties by weakening ankle extensor muscles has recently been found to produce
      compensatory changes in proprioceptive influences on the locomotor pattern.

PMID- 9928314
TI  - Neuronal basis of afferent-evoked enhancement of locomotor activity.
AB  - Activation of ankle extensor group Ia muscle spindle or Ib tendon organ afferents
      during locomotion can prolong and enhance hindlimb extensor motoneuron activity.
      A growing body of evidence suggests that these group I evoked reflexes not only
      compensate for a changing environment but also help shape extensor activity
      during normal, unperturbed locomotion. In this paper we review four mechanisms
      that underlie the group I evoked enhancement of ipsilateral extensor activity
      during locomotion. The first three are pre-motoneuronal mechanisms that are part
      of group I reflex pathway reorganization during locomotion. They are (1) a
      suppression of group I evoked nonreciprocal inhibition, (2) a release from
      inhibition of excitatory interneurons in disynaptic pathways from group I
      afferents to extensor motoneurons, and (3) longer latency excitation evoked
      through extensor portions of the locomotor circuitry. The fourth factor
      contributing to group I evoked increases in motoneuron activity during locomotion
      is the increase in motoneuron excitability produced by postsynaptic changes in
      motoneuron membrane conductances. Most results to be discussed were obtained
      during locomotion in decerebrate cats in which fictive locomotion was evoked by
      stimulation of the midbrain following neuromuscular blockade.

PMID- 9928316
TI  - Modeling of the spinal neuronal circuitry underlying locomotion in a lower
      vertebrate.
AB  - The neural circuitry generating lamprey undulatory swimming is among the most
      accessible and best known of the vertebrate neuronal locomotor systems. It
      therefore serves as an experimental model for such systems. Modeling and computer
      simulation of this system was initiated at a point when a significant part of the
      network had been identified, although much detail was still lacking. The model
      has been further developed over 10 years in close interaction with experiments.
      The local burst generating circuitry is formed by ipsilateral excitatory neurons
      and crossed reciprocal inhibitory neurons. Early models also incorporated an off
      switch lateral interneuron (L), the connectivity of which suggested it could
      contribute to burst termination at moderate to high bursting frequencies. Later
      examination of this model suggested, however, that the L interneuron was not of
      primary importance for burst termination, and this was later verified
      experimentally. Further, early models explained the effects of 5-HT on bursting
      frequency, spike frequency, and burst duration as being due to its modulatory
      action on the spike frequency adaptation of lamprey premotor interneurons. In
      current network models, accumulated adaptation is in addition the main burst
      terminating factor. Drive-related modulation of adaptation is explored as a
      mechanism for control of burst duration. This produces an adequate burst
      frequency range and a constant burst proportion within each cycle. It further
      allows for hemisegmental bursting, which has been observed experimentally. The
      local burst generator forms the basis of a network model of the distributed
      pattern generator that extends along the spinal cord. Phase constancy and
      flexibility of intersegmental coordination has been studied in such a simulated
      network. Current modeling work focuses on neuromodulator circuitry and action,
      network responses to input transients, how to model the intact versus an isolated
      piece of spinal cord, as well as on improving an earlier neuromechanical model of
      lamprey swimming.

PMID- 9928315
TI  - Frequency control of a slow oscillatory network by a fast rhythmic input: pyloric
      to gastric mill interactions in the crab stomatogastric nervous system.
AB  - The stomatogastic nervous system of the crab, Cancer borealis, produces a slow
      gastric mill rhythm and a fast pyloric rhythm. When the gastric mill rhythm is
      not active, stimulation of the modulatory commissural ganglion neuron 1 (MCN1)
      activates a gastric mill rhythm in which the lateral gastric (LG) neuron fires in
      antiphase with interneuron 1 (Int1). We present theoretical and experimental data
      that indicate that the period of the MCN1 activated gastric mill rhythm depends
      on the strength and time course of the MCN1 evoked slow excitatory synaptic
      potential (EPSP) in the LG neuron, and on the strength of inhibition of Int 1 by
      the pacemaker of the pyloric network. This work demonstrates a new mechanism by
      which a slow network oscillator can be controlled by a much faster oscillatory
      neuron or network and suggests that modulation of the slow oscillator can occur
      by direct action on the neurons and synapses of the slow oscillator, or
      indirectly by actions on the fast oscillator and its synaptic connection with the
      slow oscillator.

PMID- 9928317
TI  - Analysis and modeling of the locomotor central pattern generator as a network of
      coupled oscillators.
AB  - The primary functions of spinal locomotor central pattern generators (CPGs) are
      to provide oscillatory motor commands to individual joints or segments and to
      control the precise timing of those commands across all joints or segments for
      efficient, coordinated locomotor behavior. Our ability to understand the neuronal
      mechanisms underlying intersegmental coordination has been hampered by the
      complexity of propriospinal interconnectivity and the paucity of quantitative
      data on the magnitude and timing of those connections. Theoretical approaches
      have therefore been employed to discover general rules by which CPG-like
      oscillator systems must be constructed to produce appropriate coordinated
      locomotor behavior; the locomotor CPG is represented as a network of oscillators,
      where each oscillator generates local motor output and interoscillator coupling
      provides intersegmental coordination. Mathematical analysis of such coupled
      oscillator systems has provided a number of experimentally testable predictions
      regarding the link between coupling and coordination. Application of these
      network-level predictions to the results of electrophysiological experiments has
      required data analysis methods that can relate the behavior of the in vitro
      spinal cord to the variables employed by the mathematical model. Hence, our most
      recent work has focused on developing analytic tools for quantifying the changes
      in locomotor output that result form experimental manipulations of the
      propriospinal system in terms of frequency, intersegmental phase, and
      intersegmental correlation. Results of recent experiments can now be used to put
      further constraints on the allowable kinds of intersegmental coupling provided by
      mathematical modeling of the system.

PMID- 9928318
TI  - Intersegmental coordination of swimmeret movements: mathematical models and
      neural circuits.
AB  - Swimmerets move periodically through a cycle of power-strokes and return-strokes.
      Swimmerets on neighboring segments differ in phase by approximately 25%, and
      maintain this difference even when the period of the cycle changes from < 1 to >
      4 Hz. We constructed a minimal cellular model of the segmental pattern-generating
      circuit which incorporated its essential components, and whose dynamics were like
      those of the local circuit. Three different intersegmental coordinating units
      were known to link neighboring ganglia, but their targets are unknown. We
      constructed different intersegmental circuits which these units might form
      between neighboring cellular models, and compared their dynamics with the real
      system. One intersegmental circuit could maintain an approximately 25% phase
      difference through a range of periods. In physiological experiments, we
      identified three types of intersegmental interneurons that originate in each
      ganglion and project to its neighbors. These neurons fire bursts at certain parts
      of the swimmeret cycle in their home ganglion. These three neurons are necessary
      and sufficient to maintain normal coordination between neighboring segments.
      Their properties conform to the predictions of the cellular model.

PMID- 9928319
TI  - Differential expression and targeting of K+ channel genes in the lobster pyloric
      central pattern generator.
AB  - A molecular analysis of motor pattern generation is an essential complement to
      electrophysiological and computational investigations. In arthropods, A-channels
      are posttranslationally modified multimeric proteins containing Shaker family
      alpha-subunits that may interact with beta-subunits, gamma-subunits, and other
      auxiliary proteins. One consequence of A-channel structure is that several
      mechanisms could underlie the cell-specific differences in pyloric IAs including
      differential gene expression, alternate splicing, and posttranslational
      modifications. Oocyte expression studies, single-cell RT-PCR, and
      immunocytochemistry suggest that differential alpha-subunit gene expression is
      not a mechanism for creating pyloric IA heterogeneity, and that the same gene,
      shal, encodes the alpha-subunits for the entire family of somatic IAs in the
      pyloric network. Changes in the level of shal gene expression alter A-channel
      density between cells, but cannot account for the differences in the biophysical
      properties of the six pyloric IAs. Preliminary data suggest that the shal gene
      also encodes the A-channel alpha-subunits for the coarse and fine neuropil but
      not for most axons. A second gene, shaker, encodes the A-channel alpha-subunits
      in the majority of axons and at the neuromuscular junction. The distinct
      properties of the two types of A-channels are consistent with the different roles
      of IA at the different locations. Both the shaker and shal genes are alternately
      spliced, and investigations are under way to determine whether alternate splicing
      is a mechanism for generating pyloric IA heterogeneity.

PMID- 9928321
TI  - Reorganization of locomotor activity during development in the prenatal rat.
AB  - Development of neuronal circuits generating locomotor activity was studied using
      an isolated lumbar spinal cord preparation from fetal and neonatal rats. Bath
      application of N-methyl-D-aspartate (NMDA) or 5-HT evoked patterned motor
      activity resembling that seen during normal fictive locomotion on embryonic day
      (E) 20.5. Glycine-mediated inhibition was essential to the formation of this
      coordinated motor activity. In preparations from fetuses at the earlier stages
      (E14.5-E16.5), we observed spontaneous motoneuronal activity and chemically
      induced rhythmic bursts, which were synchronized on the two sides in the
      corresponding ventral roots. The spontaneous activity was not blocked by
      kynurenate, the glutamate receptor blocker, although it was completely abolished
      by strychnine, the glycine receptor antagonist. A brief application of glycine
      evoked excitatory responses resembling the spontaneous bursts in both time course
      and amplitude. It is concluded that glycine functions transiently as excitatory
      transmitters at these stages. These results suggest that functional change in
      glycine-induced responses during development plays an important role in
      differentiation of the neuronal circuits generating locomotion.

PMID- 9928320
TI  - Behavioral and electrophysiological analysis of Ca-activated K-channel transgenes
      in Drosophila.
AB  - The slowpoke gene of Drosophila melanogaster encodes a Ca-activated K channel.
      This gene is expressed in neurons, muscles, tracheal cells, and the copper and
      iron cells of the midgut. The gene produces a large number of alternative
      products using tissue-specific transcriptional promoters and alternative mRNA
      splicing. We have described in great depth how transcription is regulated and are
      now cataloging the tissue-specificity of different splice variants. It is
      believed that the diversity of products serves to tailor channel attributes to
      the needs of specific tissues. Electrophysiological and behavioral assays
      indicate that at least some of these products produce channels with distinct
      properties.

PMID- 9928322
TI  - Development and aminergic neuromodulation of a spinal locomotor network
      controlling swimming in Xenopus larvae.
AB  - In this article we review our research on the development and intrinsic
      neuromodulation of a spinal network controlling locomotion in a simple
      vertebrate. Swimming in hatchling Xenopus embryos is generated by a restricted
      network of well-characterized spinal neurons. This network produces a stereotyped
      motor pattern which, like real swimming, involves rhythmic activity that
      alternates across the body and progresses rostrocaudally with a brief delay
      between muscle segments. The stereotypy results from motoneurons discharging a
      single impulse in each cycle; because all motoneurons appear to behave similarly
      there is little scope for altering the output to the myotomes from one cycle to
      the next. Just one day later, however, Xenopus larvae generate a more complex and
      flexible motor pattern in which motoneurons can discharge a variable number of
      impulses which contribute to ventral root bursts in each cycle. This maturation
      of swimming is due, in part, to the influence of serotonin released from brain
      stem raphespinal interneurons whose axonal projections innervate the cord early
      in larval life. Larval swimming is differentially modulated by both serotonin and
      by noradrenaline: serotonin leads to relatively fast, intense swimming whereas
      noradrenaline favors slower, weaker activity. Thus, these two biogenic amines
      select opposite extremes from the spectrum of possible output patterns that the
      swimming network can produce. Our studies on the cellular and synaptic effects of
      the amines indicate that they can control the strength of reciprocal glycinergic
      inhibition in the spinal cord. Serotonin and noradrenaline act presynaptically on
      the terminals of glycinergic commissural interneurons to weaken and strengthen,
      respectively, crossed glycinergic inhibition during swimming. As a result,
      serotonin reduces and noradrenaline increases interburst intervals. The membrane
      properties of spinal neurons are also affected by the amines. In particular,
      serotonin can induce intrinsic oscillatory membrane properties in the presence of
      NMDA. These depolarizations are slow compared to the cycle periods during
      swimming and so may contribute to enhancement of swimming over several
      consecutive cycles of activity.

PMID- 9928323
TI  - Zebrafish as a model system for studying neuronal circuits and behavior.
AB  - Zebrafish are best known as a model system for studies of the genetics of
      development. They do, however, also offer many advantages for the study of
      neuronal circuitry because the larvae are transparent, allowing optical studies
      of neuronal activity and noninvasive photoablations of individual neurons. The
      combination of these optical methods with genetics through the use of mutant and
      transgenic lines of fish should make the zebrafish model a unique and powerful
      one among vertebrates. Here we review the strengths of the model and the
      possibilities it offers for studies of the neural basis of behavior.

PMID- 9928324
TI  - Pharmacological activation and modulation of the central pattern generator for
      locomotion in the cat.
AB  - Pharmacological agents have been shown to be capable of inducing a pattern of
      rhythmic activity recorded in muscle nerves or motoneurons of paralyzed spinal
      cats that closely resembles the locomotor pattern seen in intact cats. Further
      work, using intraperitoneal or intrathecal injections, suggests that different
      neurotransmitters may be involved in various aspects of locomotor control, e.g.,
      initiation and modulation of the pattern. Although precursors, agonists or the
      neurotransmitters themselves of several systems have been investigated
      (noradrenergic, dopaminergic, serotonergic, glutamatergic), the noradrenergic
      system seems the most efficient in triggering locomotion in complete spinal cats,
      with the alpha-2 agonists (clonidine, tizanidine, oxymetazoline) being more
      potent than the alpha-1 agonist, methoxamine. Moreover, the potency of the drugs
      may depend on the time of application after the spinal lesion. In chronic spinal
      cats capable of spontaneous walking on hindlimbs on the treadmill, all
      neurotransmitters appear to exert distinct recognizable effects on the locomotor
      pattern. More recent work also suggests that the effects of drugs may differ
      significantly depending on the type of spinal lesion. For instance, clonidine
      further reduces the level of weight support during quadrupedal locomotion of cats
      with lesions of the ventral-ventrolateral funiculi, possibly due to an
      interference of clonidine with essential compensatory mechanisms used by these
      animals to walk. Such considerations as the type of drugs, type of lesions, and
      the time after the lesion will be important for future studies in spinal cord
      injured patients.

PMID- 9928325
TI  - Evidence for a spinal central pattern generator in humans.
AB  - Non-patterned electrical stimulation of the posterior structures of the lumbar
      spinal cord in subjects with complete, long-standing spinal cord injury, can
      induce patterned, locomotor-like activity. We show that epidural spinal cord
      stimulation can elicit step-like EMG activity and locomotor synergies in
      paraplegic subjects. An electrical train of stimuli applied over the second
      lumbar segment with a frequency of 25 to 60 Hz and an amplitude of 5-9 V was
      effective in inducing rhythmic, alternating stance and swing phases of the lower
      limbs. This finding suggests that spinal circuitry in humans has the capability
      of generating locomotor-like activity even when isolated from brain control, and
      that externally controlled sustained electrical stimulation of the spinal cord
      can replace the tonic drive generated by the brain.

PMID- 9928326
TI  - Does neurorehabilitation play a role in the recovery of walking in neurological
      populations?
AB  - This review demonstrates that neurorehabilitation approaches, based on recent
      neuroscience findings, can enhance locomotor recovery after a spinal cord injury
      or stroke. Findings are presented from more than 20 clinical studies conducted by
      numerous research groups on the effect of locomotor training using either body
      weight support (BWS), functional electrical stimulation (FES), pharmacological
      approaches or a combination of them. Among the approaches, only BWS-assisted
      locomotor training has been demonstrated to have a greater effect than
      conventional or locomotor training alone. However, when study results were
      combined and weighted for the number of subjects, the results indicated that
      there is a gradient of effects from small changes with the immediate application
      of FES or BWS to larger changes when locomotor training is combined with FES or
      BWS or pharmacological approaches. The findings of these studies suggest that
      these neurorehabilitation approaches do play a role in the recovery of walking in
      subjects with spinal cord injury or stroke. Several factors contribute to the
      potential for recovery including the site, etiology, and chronicity of the
      injury, as well as the type, duration, and specificity of the intervention and
      whether interventions are combined. Furthermore, how these neurorehabilitation
      approaches may take advantage of the plasticity process following neurological
      lesion is also discussed.

PMID- 9928327
TI  - Recovery of locomotion following transplantation of monoaminergic neurons in the
      spinal cord of paraplegic rats.
AB  - Severe traumatic lesions of the spinal cord yield a permanent deficit of
      motricity in adult mammals and specifically a loss of locomotor activity of
      hindlimbs when the lesion is located at the lower thoracic level. To restore this
      function, we have developed a paradigm of transplantation in rats based on a
      transection model of the spinal cord and the subsequent injection at the
      sublesional level of a suspension of embryonic brainstem monoaminergic neurons
      which play a key role in the modulation of locomotion. A genuine locomotion was
      characterized in transplanted animals by electromyographic and
      electroneurographic recordings. This correlated with a specific reinnervation
      pattern of targets, where typical synapses were found, and with the normalization
      of biochemical parameters.

PMID- 9928328
TI  - Engines, accelerators, and brakes on functional spinal cord repair.
AB  - It is proposed that four essential goals should be met for functional repair
      after traumatic injury of the adult spinal cord. These include protecting neural
      tissue after injury and limiting secondary cell damage; replacing lost tissue
      with transplanted cell "bridges"; blocking the expression of intrinsic factors
      within the adult CNS that inhibit neural repair; and providing appropriate
      sensorimotor activity to enhance plasticity within surviving circuits, as well as
      consolidate any anatomical repair/regeneration. Included is a brief discussion on
      the approaches and limitations in the evaluation of functional spinal cord
      repair.

PMID- 9928329
TI  - Physiological and molecular characterization of interneurons in the developing
      spinal cord.

PMID- 9928330
TI  - Statistical analysis and intersegmental delays reveal possible roles of network
      depression in the generation of spontaneous activity in the chick embryo spinal
      cord.

PMID- 9928331
TI  - Organization of rhythmic motor patterns in the lumbosacral spinal cord of neonate
      mouse.

PMID- 9928332
TI  - Lumbar spinoreticular neurons in the rat: part of the central pattern generator
      for locomotion?

PMID- 9928333
TI  - Lumbar interneurons involved in the generation of fictive locomotion in cats.

PMID- 9928334
TI  - Pattern generators for muscles crossing more than one joint.

PMID- 9928335
TI  - Coherence between locomotor drive potentials and neurograms of motor pools with
      variable patterns of locomotion.

PMID- 9928336
TI  - Motor patterns for different forms of walking: cues for the locomotor central
      pattern generator.

PMID- 9928338
TI  - Crossed reciprocal inhibition and scratch rhythmogenesis in the turtle spinal
      cord.

PMID- 9928337
TI  - Segmental afferent regulation of hindlimb wiping in the spinal frog.

PMID- 9928339
TI  - Specificity of neural circuits that inhibit escape in crayfish.

PMID- 9928340
TI  - Intestinal peristalsis: a mammalian motor pattern controlled by enteric neural
      circuits.

PMID- 9928341
TI  - Comparison of NMDA-induced membrane potential oscillations and spontaneous
      rhythmic activity in the chick spinal cord.

PMID- 9928342
TI  - GABAA and GABAB modulations of synaptic transmission between L1-L2 locomotor
      network and the motoneurons in the newborn rat isolated spinal cord.

PMID- 9928343
TI  - Influence of glycinergic inhibition on spinal neuron excitability during
      amphibian tadpole locomotion.

PMID- 9928344
TI  - A novel neurotransmitter system involved in the control of motor behavior by the
      basal ganglia.

PMID- 9928345
TI  - Evidence for unstable periodic orbits in intact swimming lampreys, isolated
      spinal cords, and intermediate preparations.

PMID- 9928346
TI  - Group I disynaptic excitation in flexor and bifunctional motoneurons during
      locomotion.

PMID- 9928347
TI  - The stumbling correction reaction during fictive locomotion in the cat.

PMID- 9928348
TI  - Tonic presynaptic reduction of monosynaptic Ia EPSPs during fictive locomotion.

PMID- 9928349
TI  - The contribution of cutaneous inputs to locomotion in the intact and the spinal
      cat.

PMID- 9928350
TI  - Bilateral integration of sensorimotor signals during pedaling.

PMID- 9928351
TI  - Differential effects of the noradrenergic agonist clonidine on the locomotion of
      intact, partially and completely spinalized adult cats.

PMID- 9928353
TI  - Transplant-mediated locomotion is improved by selective serotonergic agonists.

PMID- 9928352
TI  - Kinematic analysis of recovered locomotor movements of the hindlimbs in
      paraplegic rats transplanted with monoaminergic embryonic neurons.

PMID- 9928354
TI  - Stepping in nonhuman primates with a complete spinal cord transection: old and
      new data, and implications for humans.

PMID- 9928355
TI  - Selective activation and graded recruitment of functional muscle groups through
      spinal cord stimulation.

PMID- 9928356
TI  - Effect of locomotor training related to clinical and electrophysiological
      examinations in spinal cord injured humans.

PMID- 9928357
TI  - Interlimb coupling patterns in human locomotion: are we bipeds or quadrupeds?

PMID- 9928358
TI  - Effects of long-term use of benzodiazepines on gait and standing balance in the
      elderly.

PMID- 9928359
TI  - Corticospinal function during human walking.

PMID- 9928360
TI  - Cortically controlled gait adjustments in the cat.

PMID- 9928361
TI  - Pattern generators and cortical maps in locomotion of spinal injured rats.

PMID- 9928363
TI  - Locomotion and head scanning initiated by hypothalamic stimulation are inversely
      related.

PMID- 9928362
TI  - Efferent pathways involved in the running activity originate in the ventromedial
      hypothalamus of the rat.

PMID- 9928364
TI  - Vestibulo- and reticulospinal control of the extensor half-center in locomotion.

PMID- 9928365
TI  - Locomotor behaviors in generalized convulsions are hierarchically driven from
      specific brain-stem nuclei in the network subserving audiogenic seizure.

PMID- 9928366
TI  - Intestinal epithelial-mesenchymal cell interactions.
AB  - Intestinal morphogenesis, as well as maintenance of the stem cell population and
      of the steady state between cell proliferation and differentiation, results from
      controlled cell interactions. There is growing evidence that the mesenchymal
      cells control epithelial cell behavior via their own expression and induction in
      the epithelial cells of key regulatory genes. This heterologous cross talk
      involves basement membrane molecules and paracrine factors. New in vitro/in vivo
      cellular models allowed us to analyze various mesenchymal cell phenotypes and to
      show that they exhibit different inductive properties on epithelial cells and
      that their proliferation and metabolic properties are differentially modulated by
      cytokines. Finally the epithelial-mesenchymal unit is controlled by hormonal and
      exogenous factors.

PMID- 9928367
TI  - Molecular basis of intestinal adaptation: the role of the insulin-like growth
      factor system.
AB  - Ongoing and future approaches to the cellular and molecular actions of insulin
      like growth factor I (IGF-I) and growth hormone (GH) in intestinal adaptation are
      reviewed. This is highly relevant to understanding the benefits and risks
      associated with increasing use of GH and IGF-I in patients with short bowel
      syndrome or other bowel diseases. As other growth factors share some of the
      properties of IGF-I including local expression in bowel, activation of signaling
      pathways common to other growth factors or cytokines, and modulation of action by
      growth factor-binding proteins or secreted receptor isoforms. The general issues
      and approaches outlined for IGF-I should, therefore, serve as a model for studies
      aimed at understanding the cellular and molecular mechanisms of action of other
      growth factors that are implicated in intestinal adaptation.

PMID- 9928368
TI  - Interactions between epithelial cells and immune cells in the intestine.
AB  - Not merely a passive barrier as previously assumed, epithelial cells act as
      sensitive indicators of infection that initiate defense responses. Noninvasive as
      well as invasive organisms have been demonstrated to elicit production of
      chemoattractants. That noninvasive organisms have this capacity suggests that
      receptor-mediated signaling pathways may be involved. Epithelial cells have been
      found to release both chemokines and cytokines in a precise mixture that varies
      according to the origin or maturity of the cell. Different microorganisms also
      elicit different response patterns. The information presented provides a basis
      for a new view of epithelial cell function in relation to host defense.

PMID- 9928369
TI  - The laminins: role in intestinal morphogenesis and differentiation.
AB  - Dynamic and reciprocal heterotypic cell interactions are crucial for intestinal
      morphogenesis and differentiation. This paper emphasizes the role of basement
      membrane molecules and in particular of laminins as potent mediators in this
      intercellular cross talk. Changes in the expression or localization of laminin
      isoforms or of integrins during development and cell migration strengthen the
      concept that heterogeneity in cell-matrix interactions could mediate distinct
      cell responses. A combination of genetic or biochemical approaches associated
      with in vitro models allows us to study the potential role of each laminin
      isoform in basement membrane assembly, cell migration, or cell differentiation.

PMID- 9928370
TI  - Interaction of microorganisms, epithelium, and lymphoid cells of the mucosa
      associated lymphoid tissue.
AB  - Differentiation of specific epithelial cell lineages during development, as well
      as epithelial plasticity in response to heterologous cell-to-cell cross talk
      during adult life, accounts for the large variety of functions which are
      performed by the mucosal surfaces found in the human body. Among its functions,
      the digestive mucosa is able to sample antigens and microorganisms through M
      cells of Peyer's patches' follicle-associated epithelium, in order to trigger the
      development of either tolerance or immune responses. At least in the gut, M-cell
      formation is immunoregulated. Close contact between immune cells and intestinal
      epithelium modifies the permeability of the epithelial barrier by inducing the
      conversion of enterocytes into M cells, offering at the same time an
      opportunistic way of invasion for pathogens. These lympho-epithelial interactions
      triggering M-cell formation have now been modeled in culture.

PMID- 9928371
TI  - From cytoskeleton to polarity and chemoreception in the gut epithelium.
AB  - The membrane surface of polarized epithelial cells can be separated in apical and
      basolateral domains that differ in molecular composition and function. Components
      of the cytoskeleton obviously play an important role in both generation and
      maintenance of epithelial polarity. The microtubular system is uniformly aligned
      in enterocytes and pancreatic acinar cells with the minus ends of the
      microtubules located apically and the plus ends basally. Drug-induced disassembly
      of microtubules results in mistargeting of pancreatic zymogen granules and of
      apical but not basolateral membrane proteins of enterocytes. Association of
      zymogen granules with the minus end motor protein, cytoplasmic dynein, and
      components of its receptor, dynactin, indicates that microtubules are important
      for vectorial delivery of apical but not basolateral post-Golgi vesicles. The
      lateral membrane domain of the gut epithelium is scaffolded by a spectrin-based
      membrane cytoskeleton consisting basically of actin, spectrin, and ankyrin.
      Ankyrin binds to different integral membrane proteins, such as the sodium pump in
      glandular and kidney epithelial cells or to the anion exchanger (AE2) of gastric
      parietal cells, thereby probably playing a critical role in maintenance and/or
      generation of the polarized distribution of these basolateral membrane proteins.
      Scattered epithelial cells sharing apical cytoskeletal features of gustatory
      receptor cells were identified as brush cells (tufted cells). These cells are
      rich in nitric oxide synthase and contain in their apical brush border the
      gustatory trimeric G-protein, alpha-gustducin, indicating that brush cells are
      involved in chemoreceptive signaling.

PMID- 9928373
TI  - Helicobacter pylori infection and the pathogenesis of duodenal ulceration.
AB  - Helicobacter pylori is a gram-negative spiral bacterium confined to the habitat
      of gastric-type epithelium. H. pylori causes duodenal ulceration by a cumulative
      effect of antral predominant gastritis with increased acid secretion, consequent
      gastric metaplasia in the duodenum (a site of further colonization by H. pylori),
      duodenitis, reduced duodenal bicarbonate secretion, and mucosal damage. Bacterial
      factors influence outcome. Major determinants are the production of a vacuolating
      toxin and the presence of CagA, an immunodominant product of a nonconserved gene
      cagA, a marker for the cag pathogenicity island that encodes virulence genes
      involved in induction of epithelial chemokine responses. In ulcer patients the
      mucosal immune response is polarized to a T-helper-1 (Th1) cell-mediated
      response, which may contribute to mucosal damage. Eradication of H. pylori
      restores acid output to normal. Loss of both acid and bacteria halts
      gastroduodenitis and allows ulcer healing. Gastric metaplasia does not regress in
      the short term.

PMID- 9928374
TI  - Heterogeneity of celiac disease: clinical, pathological, immunological, and
      genetic.
AB  - In this paper we consider recent new data on the pathological features of gluten
      sensitivity and on the disease-associated antigens, in the context of a
      multistage hypothesis that we have been developing for the last five years. This
      incorporates concepts of oral tolerance induction, mucosal T-cell and antibody
      mediated injury, and genetic contributions. Until now, there has been complete
      agreement that the diagnosis of celiac disease must be based on small bowel
      histology. There are patients with low-grade gluten-sensitive enteropathy, in
      whom the only morphological abnormality is a high count of intraepithelial
      lymphocytes (IEL). Some, but not all, also have positive serum IgA anti
      endomysium antibody (AEA). With good techniques, in a properly accredited
      laboratory, in a patient suspected on clinical grounds to have celiac disease, a
      positive serum IgA AEA test (perhaps, alternatively, high-titer anti
      transglutaminase by ELISA), is virtually diagnostic of the condition. Our
      hypothesis of a stepwise pathogenesis of severe gluten-sensitive enteropathy is
      re-examined in the light of these new data. It is evident that there are at least
      five different levels at which genetic influences may operate.

PMID- 9928372
TI  - Experimental models to study molecular mechanisms underlying intestinal
      inflammation.
AB  - Experimental animal models, particularly the newer mouse models, have
      convincingly demonstrated that CD+ T cells play a central role in chronic
      intestinal inflammation. Such CD4+ effector T cells are induced by the bacterial
      flora. In at least one model, it is conventional protein antigens that are
      stimulating these pathogenic T cells. The antigens driving disease seem to be a
      selective subset of immunodominant proteins, likely derived from a subset of
      organisms. Multiple genes contribute to colitis susceptibility and a number of
      these genes are being localized.

PMID- 9928375
TI  - Identification of the autoantigen of celiac disease.
AB  - Tissue transglutaminase is demonstrated to be the unknown endomysial autoantigen
      by means of immunoprecipitations from a fibrosarcoma cell culture. A novel
      hypothesis for the pathogenesis of celiac disease is formulated: The mainly
      intracellular tissue transglutaminase is released from cells during wound healing
      where it aids in stabilizing the wound area by cross-linking a small set of
      extracellular matrix components.

PMID- 9928376
TI  - Clinical models of intestinal adaptation.
AB  - Mucosal adaptation of the small intestine is morphologically restricted to only
      three different patterns, namely, atrophy, hyperplasia, and hyperregeneration.
      The hyperplastic mucosa in the experimental short bowel syndrome exhibits
      unchanged epithelial barrier properties and a differential functional adaptation
      with a 150% increase in Na-glucose cotransport but no change in electroneutral
      NaCl cotransport. In the hyperregeneratively transformed mucosa of the self
      filling blind loop of rat jejunum, absorption is seriously impaired, as indicated
      by the 80% decrease in Na-glucose cotransport. To compensate for this, epithelial
      barrier function is upregulated by an increase in tight junction complexity to
      prevent leak flux of ions and substrates. In contrast, the hyperregeneratively
      transformed mucosa in celiac sprue shows reduced tight junction complexity.
      Possible candidates responsible for the heterogeneity of tight junction
      adaptation in these conditions could be cytokines, because tumor necrosis factor
      alpha can specifically downregulate the tight junction, as indicated in the
      intestinal HT-29/B6 cell model.

PMID- 9928377
TI  - HIV/SIV enteropathy.
AB  - Evidence is increasing that HIV/SIV-induced changes in the highly differentiated
      gut-associated immune system play a central role in the pathogenesis of
      gastrointestinal manifestations in HIV/SIV infection. It has been shown in both
      humans infected with HIV and in nonhuman primates infected with SIV that a rapid,
      very early, and more pronounced loss of CD4+ T-cells occurs in the mucosa in
      comparison to the peripheral blood. The loss of this important regulatory T-cell
      subset might explain mucosal immunodeficiency with the consequence of
      opportunistic mucosal infections. In addition, there is evidence that small
      intestinal damage occurs independently of secondary infections (HIV/SIV
      enteropathy). In late-stage human disease, HIV enteropathy is characterized by
      villous atrophy with hyporegeneration and dysmaturation of intestinal epithelial
      cells. In SIV infection of macaques, villous atrophy is a very early event;
      however, it is accompanied by crypt cell hyperproliferation. Early- and late
      stage enteropathy in immunodeficiency virus infection may represent two types of
      immunologically mediated mucosal transformation in which the number and state of
      activation of regulatory T cells determine whether hypo- or hyperproliferative
      villous atrophy occurs.

PMID- 9928378
TI  - Cytokine gene transcription by NF-kappa B family members in patients with
      inflammatory bowel disease.
AB  - We examined the expression of the transcription factor NF-kappa B, a nuclear
      trans-acting factor known to play a key role in cytokine gene regulation, in
      patients with inflammatory bowel disease (IBD). It was found that LP macrophages
      in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF
      kappa B DNA-binding activity accompanied by an increased production of
      interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha. Western blot
      studies showed an increased expression of the p50 and c-rel subunits of NF-kappa
      B; however, the most striking finding was an increased expression level of NF
      kappa B p65 in patients with CD and UC. Selective downregulation of p65 in IBD
      macrophages by a specific antisense phosphorothioate oligonucleotide was
      sufficient to considerably reduce production of proinflammatory cytokines. These
      results demonstrate a characteristic increase of NF-kappa B binding levels in
      patients with IBD. The data suggest that antisense DNA targeting NF-kappa B p65
      can be used as a novel molecular approach for the treatment of patients with IBD.

PMID- 9928379
TI  - Molecular mechanisms of enteroendocrine differentiation.
AB  - Passing through a complex series of developmental steps, the visceral endoderm
      differentiates into four intestinal epithelial lineages comprising enterocytes,
      goblet cells, paneth cells, and enteroendocrine cells. The intestinal
      enteroendocrine system consists of at least 15 different cell types, which can be
      classified on the basis of morphological criteria, expression of secretory
      products, and abundance of specific marker molecules. During intestinal
      development and in the adult gut, neuroendocrine subpopulations display strictly
      controlled differences in their geographical distribution that go along with
      dramatic differences in cell type-specific gene expression. Identification to
      transcription factors and regulatory DNA elements responsible for cell-specific
      gene expression in different neuroendocrine cell types as well as various
      transgenic and "knock-out" mouse models have largely added to our understanding
      of mechanisms controlling appropriate special and temporal activation of
      enteroendocrine differentiation programs. This article reviews current in vitro
      and in vivo studies analyzing different molecular aspects of enteroendocrine
      differentiation. In addition, the influence of intestinal diseases including
      malignant transformation on enteroendocrine differentiation and the underlying
      mechanisms will be discussed.

PMID- 9928380
TI  - The regulation of matrix metalloproteinase production in human colonic
      fibroblasts.

PMID- 9928381
TI  - Regulation of mucin MUC2 gene expression during colon carcinogenesis.

PMID- 9928382
TI  - Upregulation of keratinocyte growth factor during T-cell immunity in the gut
      mucosa.

PMID- 9928383
TI  - Regulation of matrix metalloproteinase production in human fetal intestinal
      mesenchymal cells by cytokines and the bacterial superantigen Staphylococcus
      aureus enterotoxin B.

PMID- 9928384
TI  - Biochemical characterization and cloning of guinea pig intestinal phospholipase
      B.

PMID- 9928385
TI  - Regulation of protein-DNA interactions at the interferon-gamma gene promoter by
      corticosteroids. Implications for inflammatory bowel diseases.

PMID- 9928386
TI  - Influence of epidermal growth factor/transforming growth factor alpha and
      polyamines on Caco-2 cell proliferation.

PMID- 9928387
TI  - Conditionally immortalized intestinal epithelial cells. A new model for studying
      intestinal epithelial cell turnover.

PMID- 9928388
TI  - Azathioprine, mycophenolate mofetil, and methotrexate specifically modulate
      cytokine production by T cells.

PMID- 9928389
TI  - Inhibition of L-type calcium channels by somatostatins in human neuroendocrine
      tumor cells of the gut.

PMID- 9928390
TI  - High expression of inducible nitric oxide synthase correlates with intestinal
      inflammation of interleukin-2-deficient mice.
AB  - Severely inflamed colonic sections of IL-2 (-/-) mice showed up to 19-fold
      increased iNOS mRNA levels. The level of iNOS protein expression corresponded to
      the increased iNOS mRNA levels as detected by means of Western blot analysis.
      There was a clear, positive relationship between the level of iNOS expression and
      the degree of inflammation in the colonic tissue of IL-2 (-/-) and wild-type
      mice. Our data suggest that iNOS may play a key role in the pathogenesis of
      ulcerative colitis-like disease in IL-2 (-/-) mice. Further investigation should
      elucidate the impact of NO on the regulation of the inflammatory process in this
      model and might contribute to a better understanding of the role iNOS expression
      in human immune-mediated diseases.

PMID- 9928391
TI  - Effects of the anti-CD2 mAb OX34 on in vivo proliferation.
AB  - In vitro studies indicate that CD2 plays an important role in the intestinal
      immune system with regard to T cell proliferation and T helper 2 differentiation.
      We asked whether anti-CD2 mAb induces T-cell proliferation in vivo. Rats received
      anti-CD2 mAb OX34 or control mAb over 3 days. Before exsanguination BrdU was
      injected. Lymphatic organs were processed for two-color immunohistology. OX34
      depleted CD4+ but not CD8+ T cells in all organs. Remaining CD4+ T cells
      proliferated in the periarteriolar lymphocyte sheets. Surprisingly, OX34 led to
      strong proliferation of splenocytes in the red pulp. These cells were negative
      for markers of T cells, B cells, NK cells, macrophages, and myeloid cells. Taken
      together, the anti-CD2 mAb OX34 leads to proliferation of an as-yet-unidentified
      cell type in the red pulp of the spleen but not to proliferation of T cells.

PMID- 9928392
TI  - Activation and methotrexate-mediated suppression of the TNF alpha promoter in T
      cells and macrophages.

PMID- 9928393
TI  - Lysophosphatidic acid modulates intestinal epithelial cell function in vitro.

PMID- 9928394
TI  - Trefoil factor family domain peptides in murine gastrointestinal development and
      embryonic wounding.

PMID- 9928395
TI  - Role of T cells in mucosal transformation of ileoanal pouches.

PMID- 9928396
TI  - Phenotype of cells expressing matrix metalloproteinase-3 in ulcerative colitis.

PMID- 9928398
TI  - Expression of matrix metalloproteases in inflammatory bowel disease.

PMID- 9928397
TI  - Expression of functional GABAA receptors in isolated human insulinoma cells.
AB  - Pancreatic islets contain and release high concentrations of GABA. GABA is
      thought to play a paracrine role in beta-cells. Searching for a paracrine
      function of GABA in neoplastic beta-cells we performed patch-clamp studies in
      isolated human insulinoma cells. We show that human insulinoma cells can express
      functional GABAA receptors. Activation of GABAA receptors caused a reversible
      membrane depolarization in a subgroup of insulinoma cells. Membrane
      depolarization resulted in transmembraneous calcium influx through voltage-gated
      calcium channels and stimulation of insulin secretion. Insulin secretion was
      increased by the GABAA receptor agonist muscimol (50 microM) by about 280%. Thus,
      GABAA receptors can be expressed in human insulinoma cells and can regulate their
      insulin release.

PMID- 9928399
TI  - Expression of matrix metalloprotease-1 and collagen I mRNA in biopsies from
      patients with celiac disease.

PMID- 9928400
TI  - Analysis and topographical distribution of gut diamine oxidase activity in
      patients with food allergy.

PMID- 9928401
TI  - Measurement of gut diamine oxidase activity. Diamine oxidase as a new biologic
      marker of colorectal proliferation?

PMID- 9928402
TI  - The mechanism of diarrhea in HIV is based on an impaired epithelial barrier
      function that could be induced by a specific cytokine pattern.

PMID- 9928403
TI  - Identification of CMV-specific immunoglobulin production by intestinal biopsies
      of AIDS patients with CMV enteritis.

PMID- 9928404
TI  - Similar proviral load but increased HIV-1 p24 in the intestinal mucosa compared
      to the peripheral blood in HIV-infected patients.

PMID- 9928405
TI  - Intestinal antibodies against gliadin, tissue-transglutaminase, beta
      lactoglobulin, and ovalbumin in patients with irritable bowel syndrome.

PMID- 9928406
TI  - Cartography of barrier defects in human colon by low-resolution conductance
      scanning.

PMID- 9928408
TI  - Ion transport in rat colon measured by medium-resolution conductance scanning.

PMID- 9928407
TI  - Murine model of oral tolerance. Induction of Fas-mediated apoptosis by blockade
      of interleukin-12.
AB  - We explored the immunological mechanisms underlying the development of oral
      tolerance with the use of ovalbumin (OVA) T-cell receptor (TCR)-transgenic mice.
      Feeding high doses of OVA induced tolerance in the peripheral lymphoid tissues,
      and the degree of peripheral tolerance was enhanced when antigen feeding was
      combined with systemic administration of antibodies to interleukin-12 (anti-IL
      12). Using the TUNEL technique by which apoptotic cells can be specifically
      identified, we found evidence that peripheral clonal deletion occurs in OVA-TCR
      transgenic mice in vivo after oral antigen delivery and treatment with anti-IL
      12, but only to a minor degree after antigen feeding alone. The mechanism that
      accounts for the dramatic loss of peripheral cells is Fas-mediated, since > 90%
      of antigen-specific Fas+ T cells were lost. In addition, antagonizing Fas but not
      TNF reversed the phenomenon when cells were stimulated in vitro. These findings
      suggest that IL-12 negatively regulates apoptosis, a major mechanism of
      peripheral tolerance. A combination of oral antigen feeding and administration of
      anti-IL-12 may thus be useful in the treatment of autoimmune diseases and may be
      a potent means to modulate peripheral tolerance.

PMID- 9928409
TI  - CD44 expression in colorectal cancer.

PMID- 9928410
TI  - Expression of inducible nitric oxide synthase in duodenal tissue of HIV-infected
      patients.

PMID- 9928411
TI  - Activation and methotrexate-mediated suppression of the TNF alpha promoter in T
      cells and macrophages.

PMID- 9928412
TI  - Mycophenolate mofetil for treatment of active inflammatory bowel disease.
      Clinical and immunological studies.

PMID- 9928413
TI  - Regulation of protein-DNA interactions at the interferon-gamma gene promoter by
      corticosteroids.

PMID- 9928414
TI  - Aging: phenomena and theories.
AB  - Aging is the accumulation of diverse adverse changes that increase the risk of
      death. These changes can be attributed to development, genetic defects, the
      environment, disease, and the inborn aging process. The chance of death at a
      given age serves as a measure of the number of accumulated aging changes, that
      is, of physiologic age, and the rate of change of this measure, as the rate of
      aging. As living conditions in a population approach optimum, the curve of the
      logarithm of the chance of death versus age shifts towards a limit determined by
      the sum of (1) the irreducible contributions to the chance of death by aging
      changes that can be prevented to varying degrees, and (2) those due to the
      intrinsic aging process. In the developed countries living conditions are now
      near optimum, and the ALE-Bs are about 6-9 years less than the potential maximum
      of around 85 years. The inborn aging process is now the major risk factor for
      disease and death after about age 28. By age 28 only 1 to 2% of a cohort is dead,
      the remaining 98 to 99% die at an exponentially increasing rate determined by the
      aging process. This process ensures that few reach 100 years and none exceed
      about 122 years. Many theories have been advanced to account for the aging
      process. No single theory is generally accepted. Theories that can contribute to
      the important practical goal of increasing the healthy, useful span of humans
      will endure.

PMID- 9928415
TI  - Genes involved in the control of cellular proliferative potential.
AB  - Evidence that control of cellular proliferative potential may be linked to
      telomere length, along with data indicating that other factors may also be
      involved, will be reviewed. According to the telomere hypothesis of senescence,
      the sequential loss of telomeric repeat DNA that occurs during the replication of
      normal somatic cells eventually dictates the onset of the permanently
      nonreplicative state known as senescence. Many immortalized cells express
      telomerase, a ribonucleoprotein enzyme that replaces the telomeric DNA that would
      otherwise be lost due to replication. However, some immortalized human cells may
      avoid telomeric shortening without using telomerase. The mechanism involved is
      currently unknown, but other eukaryotes are able to replace telomeric DNA through
      (1) recombination and copy switching or (2) retrotransposition. Human fibroblasts
      that lose p53 function proliferate a limited number of times beyond the
      population-doubling level at which their normal counterparts become senescent.
      Lack of functional retinoblastoma (Rb) protein (or equivalent events, such as
      loss of p16INK4 function, resulting in abrogation of Rb regulatory activity) also
      permits a temporary extension of proliferative potential. The p53 and pRb effects
      are additive, indicating that they exert their control on proliferative potential
      separately. The temporary life span extension associated with loss of p53 and/or
      Rb pathway function is accompanied by continued telomere shortening. The
      proliferation arrest that eventually ensues in p53-minus cells or in p53-minus/Rb
      minus cells may be regarded as terminal proliferation arrest states serving as a
      backup to senescence. p53-minus/Rb-minus cells cannot proliferate further unless
      they acquire the ability to prevent telomeric shortening. Somatic cell
      hybridization and microcell-mediated chromosome transfer experiments indicate
      that immortalization involves the loss of function of other, as yet unidentified,
      genes; some of these may normally repress telomerase expression in somatic cells.

PMID- 9928416
TI  - Somatic mutation and aging.
AB  - A key prediction of the somatic mutation theory of aging is that there is an
      invariant relationship between life span and the number of random mutations. A
      number of studies at a number of gene loci have shown that somatic mutations of a
      variety of types accumulate with age. Dietary restriction, which prolongs life
      span, results in slowed accumulation of HPRT mutants in mice. Conversely,
      senescence-accelerated mice, which have been bred to have a shortened life span,
      show accelerated accumulation of somatic mutations.

PMID- 9928417
TI  - Chromosomal damage rate, aging, and diet.
AB  - Chromosomal damage as measured by frequency of translocations, acentric
      fragments, telomere shortening, nondisjunction, chromosome loss, aneuploidy, and
      micronucleus formation has been shown to increase progressively with age. Using
      the cytokinesis-block micronucleus technique, which provides an efficient measure
      of chromosomal breakage and loss, we have been able to show that aging can
      explain at least 25% of the variation in chromosomal damage rate in lymphocytes
      from both males and females. We have also performed cross-sectional and placebo
      controlled intervention studies to determine the relationship between the
      micronucleus (MN) frequency in lymphocytes and diet, and blood status for
      vitamins C, E, B12, and folic acid. Our studies have shown that MN frequency in
      the 41- to 60-year age group is significantly lower in vegetarians when compared
      to nonvegetarians, but the reverse was true in males aged between 20 and 40
      years. This was accounted for by a deficient/low B12 status in vegetarian males;
      there was no difference in the MN frequency of vegetarian and nonvegetarian
      subjects aged between 61 and 90 years. Results from this study also showed
      significant negative correlations of MN frequency with folic acid and vitamin B12
      but not with vitamin C or vitamin E. In separate studies on healthy men aged 50
      70, we have verified the significant negative correlation between vitamin B12
      status in plasma and MN frequency (r = -0.315, p = 0.013) in subjects who were
      not vitamin B12 deficient and observed a significant positive correlation between
      MN frequency and homocysteine status (r = 0.414, p = 0.0086) in those men who
      were not vitamin B12 and/or folate deficient. These data suggest that MN
      frequency is minimized when plasma B12 is above 300 pmol/L and plasma
      homocysteine is below 7.5 mumol/L. Double-blind placebo-controlled intervention
      studies conducted over four months have shown that above RDI intake of vitamin E
      (30 x RDI) or folic acid (10 x RDI) did not produce a significant reduction in MN
      frequency in men aged 50-70 years. In the latter case plasma homocysteine was
      reduced from a mean value of 9.33 mumol/L to 8.51 mumol/L, a level that does not
      correspond with minimization of MN frequency. We have also tested the hypothesis
      that moderate wine drinking can protect against the DNA-damaging effect of
      hydrogen peroxide and found that there was a strong ex vivo inhibition (> 70%) of
      hydrogen peroxide-induced MN frequency by plasma samples from blood collected one
      hour after consumption of red or white wine, as compared to plasma samples
      collected immediately before wine consumption (p = 0.0008). However, only samples
      following red wine consumption produced a significant reduction in baseline MN
      frequency. The above results suggest that chromosome damage can be modulated,
      under selected circumstances, by diverse dietary factors.

PMID- 9928419
TI  - The nature of gerontogenes and vitagenes. Antiaging effects of repeated heat
      shock on human fibroblasts.
AB  - Our survival and the physical quality of life depends upon an efficient
      functioning of various maintenance and repair processes. This complex network of
      the so-called longevity assurance processes is composed of several genes, termed
      vitagenes. The homeodynamic property of living systems is a function of such a
      vitagene network. Because aging is characterized by the failure of homeodynamics,
      a decreased efficiency and accuracy of the vitagene network can transmutate it
      into a gerontogene network. It is not clear how various components of the
      vitagene network operate and influence each other in a concordant or a discordant
      manner. Experimental strategies through which this transmutation of vitagenes
      into virtual gerontogenes may be elucidated include induction of molecular
      damage, antisense intervention, and genetic screening for varied efficiencies of
      the members of the vitagene family. A reversal of this approach by maintaining or
      recovering the activity of vitagenes will lead to a delay of aging, a decreased
      occurrence of age-related diseases, and a prolongation of a healthy life span.

PMID- 9928420
TI  - Causes of aging.
AB  - A broad biological approach makes it possible to understand why aging exists and
      also why different mammalian species have very different maximum longevities. The
      adult organism is maintained in a functional state by at least ten major
      mechanisms, which together constitute a substantial proportion of all biological
      processes. These maintenance mechanisms eventually fail, because the evolved
      physiological and anatomical design of higher animals is incompatible with
      continual survival. The life span of each mammalian species depends on the
      efficiency of maintenance of their cells, tissues, and organs, and there is much
      evidence that such maintenance is more effective in long-lived species, such as
      humans, than in short-lived small mammals. It is also evident that there is an
      inverse relationship between reproductive potential and longevity, which would be
      expected if available metabolic resources are shared between investment in
      reproduction and investment in the preservation of the adult body. It is proposed
      that the eventual failure of maintenance leads to the pathological changes seen
      in age-associated disease. Although we now have a biological understanding of the
      aging process, much future research will be needed to uncover the cellular and
      molecular changes that give rise to age-associated diseases. The major aim of
      such research is to devise procedures to delay or prevent the onset of these
      diseases.

PMID- 9928418
TI  - Pluripotent protective effects of carnosine, a naturally occurring dipeptide.
AB  - Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in
      brain, innervated tissues, and the lens at concentrations up to 20 mM in humans.
      In 1994 it was shown that carnosine could delay senescence of cultured human
      fibroblasts. Evidence will be presented to suggest that carnosine, in addition to
      antioxidant and oxygen free-radical scavenging activities, also reacts with
      deleterious aldehydes to protect susceptible macromolecules. Our studies show
      that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of
      proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose
      glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation
      product). Additionally we show that carnosine inhibits formation of MDA-induced
      protein-associated advanced glycosylation end products (AGEs) and formation of
      DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular
      level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO
      cells, and cultured rat brain endothelial cells against the toxic effects of
      formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose
      mixture. Interestingly, carnosine protected cultured rat brain endothelial cells
      against amyloid peptide toxicity. We propose that carnosine (which is remarkably
      nontoxic) or related structures should be explored for possible intervention in
      pathologies that involve deleterious aldehydes, for example, secondary diabetic
      complications, inflammatory phenomena, alcoholic liver disease, and possibly
      Alzheimer's disease.

PMID- 9928421
TI  - Intrinsic and extrinsic factors in muscle aging.
AB  - The regenerative potential of skeletal muscle, and overall muscle mass, decline
      with age. This regenerative potential may be influenced by autocrine growth
      factors intrinsic to the muscle itself. Extrinsic host factors that may influence
      muscle regeneration include hormones, growth factors secreted in a paracrine
      manner by accessory cells, innervation, and antioxidant mechanisms. Unaccustomed
      exercise, which involves mechanical overload of myofibers, provides a convenient
      method for studying muscle regeneration in both humans and animal models. An
      inflammatory response ensues in which distinctive populations of macrophages
      infiltrate the affected tissue: some of these macrophages are involved in
      phagocytosis of damaged fibers; other macrophages arriving at later times may
      deliver growth factors or cytokines that promote regeneration. These include
      fibroblast growth factor and insulin-like growth factor, which are important
      regulators of muscle precursor cell growth and differentiation, as well as nerve
      growth factor, which is essential for maintenance or reestablishment of neuronal
      contact. Other cytokines, including interleukin-1, tumor necrosis factor,
      interleukin-15, and ciliary neurotrophic factor, have a strong influence on the
      balance between muscle protein synthesis and breakdown. The functional activity
      of invading macrophages can be influenced by age, by factors in myofibers and
      extracellular matrix, and can be influenced systemically by the antioxidant
      status of the host.

PMID- 9928422
TI  - Age-associated changes in the response of skeletal muscle cells to exercise and
      regeneration.
AB  - This paper looks at the effects of aging on the response of skeletal muscle to
      exercise from the perspective of the behavior of muscle precursor cells (widely
      termed satellite cells or myoblasts) and regeneration. The paper starts by
      outlining the ways in which skeletal muscle can respond to damage resulting from
      exercise or other trauma. The age-related changes within skeletal muscle tissue
      and the host environment that may affect the proliferation and fusion of
      myoblasts in response to injury in old animals are explored. Finally, in vivo and
      in vitro data concerning the wide range of signaling molecules that stimulate
      satellite cells and other aspects of regeneration are discussed with respect to
      aging. Emphasis is placed on the important role of the host environment,
      inflammatory cells, growth factors and their receptors (particularly for FGF-2),
      and the extracellular matrix.

PMID- 9928423
TI  - Age-associated changes in the innervation of muscle fibers and changes in the
      mechanical properties of motor units.
AB  - In both humans and animals there is a progressive loss of muscle strength with
      age. Tests of handgrip and knee extension in men show that some decline in
      strength is evident by the age of 55 years and is pronounced by the age of 65,
      compared with the 25- to 35-year period when strength is at a maximum. A
      comparable age-related decline in peak force development has also been shown in
      hind-limb muscles of aged rats. Motoneurons and consequently motor units are lost
      with age, and this is apparent in man after the age of 60. Again, a comparable
      decline has been demonstrated in the motoneuron population of hindlimb muscles of
      rats aged 20-24 months. Loss of motoneurons in young adults (through either
      injury or disease) results in the remaining intact motoneurons sprouting to
      innervate the denervated fibers. This capacity for sprouting has been shown to be
      seriously impaired in the hindlimb muscles of aged rats. Furthermore, the well
      established relationship between motor unit size and fatigability (smaller units
      tend to be more fatigue resistant) also tends to break down, with large units
      just as likely to be fatigable as fatigue resistant. The normally large,
      fatigable motor units also appear to be reduced in size in the aged muscles. The
      age-related loss of motoneurons and associated loss of muscle fibers accounts in
      part for the reduced functional capacity of muscle with age. The reason for the
      impairment of the aged motoneuron remains to be investigated, but it may relate
      to the integrity of the oxidative metabolic pathways within the cell, given that
      mitochondrial respiratory chain function is known to be reduced with age.

PMID- 9928424
TI  - Oxidative stress and aging. Role of exercise and its influences on antioxidant
      systems.
AB  - Strenuous exercise is characterized by an increased oxygen consumption and
      disturbance of intracellular prooxidant-antioxidant homeostasis. At least three
      biochemical pathways, that is, mitochondrial electron transport chain, xanthine
      oxidase, and polymorphoneutrophil have been identified as potential sources of
      intracellular free radical generation during exercise. These deleterious reactive
      oxygen species pose a serious threat to the cellular antioxidant defense system,
      such as diminished reserve of antioxidant vitamins and glutathione, and have been
      shown to cause oxidative damage in exercising and/or exercised muscle and other
      tissues. However, enzymatic and nonenzymatic antioxidants have demonstrated great
      versatility and adaptability in response to acute and chronic exercise. The
      delicate balance between prooxidants and antioxidants during exercise may be
      altered with aging. Study of the complicated interaction between aging and
      exercise under the influence of reactive oxygen species would provide more
      definitive information as to how much aged individuals should be involved in
      physical activity and whether supplementation of nutritional antioxidants would
      be desirable.

PMID- 9928425
TI  - Mitochondrial aging: open questions.
AB  - Interest in the role of mitochondria in aging has intensified in recent years.
      This focus on mitochondria originated in part from the free radical theory of
      aging, which argues that oxidative damage plays a key role in degenerative
      senescence. Among the numerous mechanisms known to generate oxidants, leakage of
      the superoxide anion and hydrogen peroxide from the mitochondrial electron
      transport chain are of particular interest, due to the correlation between
      species-specific metabolic rate ("rate of living") and life span.
      Phenomenological studies of mitochondrial function long ago noted a decline in
      mitochondrial function with age, and on-going research continues to add to this
      body of knowledge. The extranuclear somatic mutation theory of aging proposes
      that the accumulation of mutations in the mitochondrial genome may be responsible
      in part for the mitochondrial phenomenology of aging. Recent studies of
      mitochondrial DNA (mtDNA) deletions have shown that they increase with age in
      humans and other mammals. Currently, there exist numerous important and
      fundamental questions surrounding mitochondria and aging. Among these are (1) How
      important are mitochondrial oxidants in determining overall cellular oxidative
      stress? (2) What are the mechanisms of mitochondrial oxidant generation? (3) How
      are lesions and mutations in mtDNA formed? (4) How important are mtDNA lesions
      and mutations in causing mitochondrial dysfunction? (5) How are mitochondria
      regulated, and how does this regulation change during aging? (6) What are the
      dynamics of mitochondrial turnover? (7) What is the relationship between
      mitochondrial damage and lipofuscinogenesis? (8) What are the relationships among
      mitochondria, apopotosis, and aging? and (9) How can mitochondrial function (ATP
      generation and the establishment of a membrane potential) and dysfunction
      (oxidant generation) be modulated and degenerative senescence thereby treated?

PMID- 9928426
TI  - Mitochondrial DNA mutations and age.
AB  - Apopotic cell death is reported to be prominent in the stable tissues of the
      failing heart, in cardiomyopathies (CM), in the sinus node of complete heart
      block, in B cells of diabetes mellitus, and in neurodegenerative diseases.
      Recently, mitochondrial (mt) control of nuclear apoptosis was demonstrated in the
      cell-free system. The mt bioenergetic crisis induced by exogenously added factors
      such as respiratory inhibitors leads to the collapse of mt transmembrane
      potential, to the opening of the inner membrane pore, to the release of the
      apoptotic protease activating factors into cytosol, and subsequently to nuclear
      DNA fragmentation. However, the endogenous factor for the mt bioenegertic crisis
      in naturally occurring cell death under the physiological conditions without
      vascular involvement has remained unknown. Recently devised, the total detection
      system for deletion demonstrates the extreme fragmentation of mtDNA in the
      cardiac myocytes of senescence, and mt CM harboring maternally inherited point
      mutations in mtDNA and on the cultured cell line with or without mtDNA disclosed
      that mtDNA is unexpectedly fragile to hydroxyl radial damage and hence to oxygen
      stress. The great majority of wild-type mtDNA fragmented into over two hundreds
      types of deleted mtDNA related to oxidative damage, resulting in pleioplasmic
      defects in the mt energy transducing system. The mtDNA fragmentation to this
      level is demonstrated in cardiac myocytes of normal subjects over age 80, of an
      mtCM patient who died at age 20 and one who died at age 19, of a recipient of
      heart transplantation at age 7 with severe mtCM, and in mtDNA of a cultured cell
      line under hyperbaric oxygen stress for two days, leading a majority of cells to
      apoptotic death on the third day. The extreme fragility of mtDNA could be the
      missing link in the apoptosis cascade that is the physiological basis of aging
      and geriatrics of such stable tissues as nerve and muscle.

PMID- 9928427
TI  - Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of
      mitochondrial respiratory function.
AB  - Mitochondrial respiration and oxidative phosphorylation are gradually uncoupled,
      and the activities of the respiratory enzymes are concomitantly decreased in
      various human tissues upon aging. An immediate consequence of such gradual
      impairment of the respiratory function is the increase in the production of the
      reactive oxygen species (ROS) and free radicals in the mitochondria through the
      increased electron leak of the electron transport chain. Moreover, the
      intracellular levels of antioxidants and free radical scavenging enzymes are
      gradually altered. These two compounding factors lead to an age-dependent
      increase in the fraction of the ROS and free radical that may escape the defense
      mechanism and cause oxidative damage to various biomolecules in tissue cells. A
      growing body of evidence has established that the levels of ROS and oxidative
      damage to lipids, proteins, and nucleic acids are significantly increased with
      age in animal and human tissues. The mitochondrial DNA (mtDNA), although not
      protected by histones or DNA-binding proteins, is susceptible to oxidative damage
      by the ever-increasing levels of ROS and free radicals in the mitochondrial
      matrix. In the past few years, oxidative modification (formation of 8-hydroxy-2'
      deoxyguanosine) and large-scale deletion and point mutation of mtDNA have been
      found to increase exponentially with age in various human tissues. The
      respiratory enzymes containing the mutant mtDNA-encoded defective protein
      subunits inevitably exhibit impaired respiratory function and thereby increase
      electron leak and ROS production, which in turn elevates the oxidative stress and
      oxidative damage of the mitochondria. This vicious cycle operates in different
      tissue cells at different rates and thereby leads to the differential
      accumulation of mutation and oxidative damage to mtDNA in human aging. This may
      also play some role in the pathogenesis of degenerative diseases and the age
      dependent progression of the clinical course of mitochondrial diseases.

PMID- 9928428
TI  - Tissue-specific distribution of multiple mitochondrial DNA rearrangements during
      human aging.
AB  - Mitochondria, according to the free radical theory of aging, are the major source
      of reactive oxygen species (ROS). The results, presented in this paper, question
      the role of reactive oxygen species in contributing significantly to the extent
      of mitochondrial bioenergy degradation of the tissues, which can be correlated
      with mtDNA rearrangements. We report here that mtDNA rearrangements, including
      deletions and duplications, in tissues from human aged subjects, occur in levels
      ranging from very low in liver, to considerable in cardiac muscle, to almost
      total in skeletal muscle. The extent of mtDNA rearrangements is correlated at
      both the individual tissue and cell level with cytochrome oxidase (COX) activity
      as the exemplifier of cellular bioenergy capacity. Thus, the ROS proposal in its
      simplest form as it affects mtDNA and mitochondrial electron transport system is
      not supported by the available data.

PMID- 9928429
TI  - Influences of caloric restriction on age-associated skeletal muscle fiber
      characteristics and mitochondrial changes in rats and mice.
AB  - The effect of caloric restriction (CR) initiated in adult rats (17 months of age)
      on the abundance of deleted mitochondrial genomes, mitochondrial enzymatic
      abnormalities, and fiber number was examined in rat skeletal muscle. Vastus
      lateralis muscle from young (3-4 months) ad libitum-fed, old (30-32 months)
      restricted (35% and 50% CR, designated CR35 and CR50, respectively), and old ad
      libitum-fed rats (29 months) was studied. CR preserved fiber number and fiber
      type composition in the CR50 rats. In the old rats from all groups, individual
      fibers were found with either no detectable cytochrome-c oxidase activity (COX-),
      hyperactive for succinate dehydrogenase activity (SDH++), or both COX- and SDH++.
      Muscle from the CR50 rats contained significantly fewer COX- and SDH++ fibers
      than did the muscle from the CR35 rats. CR50 rats also had significantly lower
      numbers of mtDNA deletion products in two (adductor longus and soleus) of the
      four muscles examined compared to CR35 rats. These data indicate that CR begun in
      late middle age can retard age-associated fiber loss and fiber-type changes as
      well as lower the number of skeletal muscle fibers exhibiting mitochondrial
      enzyme abnormalities. CR can also decrease the accumulation of deleted
      mitochondrial genomes.

PMID- 9928430
TI  - The effects of dietary restriction on mitochondrial dysfunction in aging.
AB  - Age-associated alterations in the mitochondrial electron transport system (ETS)
      may lead to free radical generation and contribute to aging. The complexes of the
      ETS were screened spectrophotometrically in gastrocnemius of young (10 month) as
      well as older (20 and 26 month) B6C3F1 female mice fed an ad libitum (AL) diet or
      a restricted (DR) in total calories diet (40% less food than AL mice). The
      activities of complexes I, III, and IV decreased significantly by 62%, 54%, and
      74%, respectively, in old AL mice (AL20) compared to young AL mice (AL10).
      Complexes I, III, and IV from DR10 mice had activities that were significantly
      lower than those seen in AL10 mice (suggesting a lower total respiratory rate or
      improved efficiency). By contrast, complex II activity did not decrease with age
      (actually increased, but not significantly) in AL20 mice. Complex II was
      decreased across age in DR mice. K(m) for ubiquinol-2 of complex III was
      significantly increased in AL10 animals (0.33 mM vs. 0.26 mM in DR10 mice) and
      was further increased with aging (0.44 mM in AL20 vs. 0.17 mM in DR20 mice). This
      suggests obstruction of binding, inhibition of electron flow in aging, which
      could yield premature product release as a free radical. Total complex IV by Vmax
      was highest in AL10 mice, but the proportion of complex as high-affinity sites
      was lower (69%) than in either DR10 (80%) or DR20 (80%). The percentage of high
      affinity sites decreased to only 45% in AL20 mice, and Vmax was reduced by 75
      percent. In AL26 mice high-affinity sites decreased to 33 percent. At physiologic
      concentration of reduced cytochrome c, significant dysfunction of complex IV in
      AL20 or AL26 mice would be expected with obstruction of overall electron
      transport. The age-associated loss of activity and function of complexes I, III,
      and IV may contribute to increased free radical production. Lack of sufficient
      DNA repair in mitochondria and juxtaposition to the ETS adds to susceptibility
      and accumulation of mtDNA and other mitochondrial macromolecular damage. DR seems
      to retard this deterioration of mitochondrial respiratory function by preserving
      enzymatic activities and function.

PMID- 9928431
TI  - The universality of bioenergetic disease. Age-associated cellular bioenergetic
      degradation and amelioration therapy.
AB  - During the present century there has been a dramatic change in life expectancy in
      advanced societies, now exceeding 80 years. As distinct from life expectancy,
      life potential is said to be at least 120 years, so that the continuing increase
      in knowledge has the potential for further major changes in the survival of
      humans conceivably in the near future. This presentation will be concerned with
      one aspect of the development of biomedical advances related in part to a concept
      of an "age-related universality of bioenergetic disease," and its potential
      amelioration and proposed impact on age-related disease and lifestyle. Aging is a
      complex biological process associated with a progressive decline in the
      physiological and biochemical performance of individual tissues and organs,
      leading to age-associated disease and senescence. Consideration of the
      progressive accumulation of mitochondrial DNA mutation with age and the
      tissue/cellular bioenergy decline associated with the aging process has led us to
      the proposal of a "universality of bioenergetic disease" and the potential for a
      redox therapy for the condition. This concept envisages that a tissue
      bioenergetic decline will be intrinsic to various diseases of the aged and
      thereby contribute to their pathology, in particular, heart failure, degenerative
      brain disease, muscle and vascular diseases, as well as other syndromes. The
      information and concepts embodied in this proposal will be reviewed under the
      following headings: (1) mitochondrial DNA deletion mutation in some tissue is
      very extensive and shows mosaicism; (2) age-associated tissue/cellular bioenergy
      mosaic closely corresponds to the mtDNA profile; (3) cellular bioenergy as a
      function of mitochondrial bioenergy, glycolysis, and plasma membrane
      oxidoreductase; (4) redox therapy for the reenergization of cells, tissues, and
      whole organs. A redox therapy based on coenzyme Q10 has demonstrated profound
      alteration in heart function of old rats; no significant effect was observed with
      young rats.

PMID- 9928432
TI  - Mitochondrial decay in aging. Reversal through supplementation of acetyl-L
      carnitine and N-tert-butyl-alpha-phenyl-nitrone.
AB  - We show that mitochondrial function in the majority of hepatocytes isolated from
      old rats (24 mo) is significantly impaired. Mitochondrial membrane potential,
      cardiolipin levels, respiratory control ratio, and overall cellular O2
      consumption decline, and the level of oxidants increases. To examine whether
      dietary supplementation of micronutrients that may have become essential with age
      could reverse the decline in mitochondrial function, we supplemented the diet of
      old rats with 1% (w/v) acetyl-L-carnitine (ALCAR) in drinking water. ALCAR
      supplementation (1 month) resulted in significant increases in cellular
      respiration, mitochondrial membrane potential, and cardiolipin values. However,
      supplementation also increased the rate of oxidant production, indicating that
      the efficiency of mitochondrial electron transport had not improved. To
      counteract the potential increase in oxidative stress, animals were administered
      N-tert-butyl-alpha-phenyl-nitrone (30 mg/kg) (PBN) with or without ALCAR. Results
      showed that PBN significantly lowered oxidant production as measured by 2,7'
      dichlorofluorescin diacetate (DCFH), even when ALCAR was coadministered to the
      animals. Thus, dietary supplementation with ALCAR, particularly in combination
      with PBN, improves mitochondrial function without a significant increase in
      oxidative stress.

PMID- 9928433
TI  - Mitochondrial free radical production and aging in mammals and birds.
AB  - The mitochondrial rate of oxygen radical (ROS) production is negatively
      correlated with maximum life span potential (MLSP) in mammals following the rate
      of living theory. In order to know if this relationship is more than
      circumstantial, homeothermic vertebrates with MLSP different from that predicted
      by the body size and metabolic rate of the majority of mammals (like birds and
      primates) must be studied. Birds are unique because they combine a high rate of
      basal oxygen consumption with a high MLSP. Heart, brain, and lung mitochondrial
      ROS production and free radical leak (percent of total electron flow directed to
      ROS production) are lower in three species of birds of different orders than in
      mammals of similar body size and metabolic rate. This suggests that the capacity
      to show a low rate of ROS production is a general characteristic of birds. Using
      substrates and inhibitors specific for different segments of the respiratory
      chain, the main ROS generator site (responsible for those bird-mammalian
      differences) in state 4 has been localized at complexes I and III in heart
      mitochondria and only at complex I in nonsynaptic brain mitochondria. In state 3,
      complex I is the only generator in both tissues. The results also suggest that
      the iron-sulphur centers are the ROS generators of complex I. A general mechanism
      that allows pigeon mitochondria to show a low rate of ROS production can be the
      capacity to maintain a low degree of reduction of the ROS generator site. In
      heart mitochondria, this is supplemented with a low rate of oxygen consumption
      physiologically compensated with a comparatively higher heart size. A low rate of
      free radical production near DNA, together with a high rate of DNA repair, can be
      responsible for the slow rate of accumulation of DNA damage and thus the slow
      aging rate of longevous animals.

PMID- 9928434
TI  - Oxidative damage in the senescence-accelerated mouse.
AB  - The senescence-accelerated mouse (SAM) exhibited a shortened life span (about 18
      months) and early manifestation of various signs of senescence, including changes
      in physical activity, skin, and spinal curvature. The mechanism of senescence
      acceleration in SAM is thought to be related to free radical damage. Oxidative
      phosphorylation was estimated in liver mitochondria from SAMPS and the senescence
      resistant subtrain, SAMR1. The respiratory control ratio decreased during aging,
      and the ATP/O, an index of ATP synthesis, was depressed at 18 months of age in
      SAMPS. DNP-dependent uncoupled respiration in liver mitochondria was markedly
      decreased, and active uptake of calcium was markedly dysfunctional with aging.
      These findings suggest that the functional disorders in mitochondria may be
      closely related to the shorter life span of SAMPS. White-footed (WF) mice can
      live at least to 5.5 years, when some animals are still capable of reproducing
      and their external body condition remains healthy. The mitochondrial functions
      were examined in the same way as in the SAM experiments. However, no particular
      finding responsible for their longevity was observed in WF mice at 3 and 12
      months old. More comprehensive examinations on more aged WF mice are needed for
      explanation of their greater longevity.

PMID- 9928435
TI  - How best to ameliorate the normal increase in mitochondrial superoxide formation
      with advancing age.

PMID- 9928436
TI  - Membrane and receptor modifications of oxidative stress vulnerability in aging.
      Nutritional considerations.
AB  - Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis
      of age-related decrements in neuronal function and that OS vulnerability
      increases as a function of age. In addition to decreased endogenous protection,
      increases in OS vulnerability may result from changes in membrane lipids and
      distribution of receptor subtype. Using a PC-12 cell model system, we have shown
      that H2O2 or dopamine (DA) exposure induced deficits in the cell's ability to
      clear (extrude/sequester, E/S) Ca2+ that are similar to those seen in aging. When
      plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM
      metabolite, sphingosine-1-phosphate was increased to the same levels as those
      seen in aging, and enhancement of OS-induced decreases in calcium E/S following
      KCL depolarization was observed. Differential decreases in CA2+ E/S were also
      seen following DA-induced OS in COS-7 cells transfected with one of five
      muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4
      receptors showed significantly greater vulnerability to OS (as expressed by
      greater decrements in calcium E/S and cell death) than those transfected with M3
      or M5 receptors. The vitamin E analogue, Trolox, and the nitrone-trapping agent,
      PBN, were not effective in altering E/S decrements but were effective in
      preventing cell death 24 h after OS exposure. These findings suggest that
      putative regional (e.g., striatum and hippocampus) increases in OS vulnerability
      and loss of neuronal function in aging may be dependent upon membrane SPM
      concentration and receptor subtype. In related studies, attempts were made to
      determine whether increased OS protection via nutritional increases in
      antioxidant levels in rats [using diets supplemented with vitamin E (500IU/kg),
      strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg
      DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against
      exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated
      that these diets were effective in preventing OS-induced decrements in several
      parameters (e.g., nerve growth factor decreases), suggesting that although there
      may be increases in OS vulnerability in aging, phytochemicals present in
      antioxidant-rich foods may be beneficial in reducing or retarding the functional
      central nervous system deficits seen in aging or oxidative insult.

PMID- 9928437
TI  - Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging
      and disease.
AB  - Oxidative stress is apparent in pathology associated with aging and many age
      related, chronic diseases, including atherosclerosis, diabetes mellitus,
      rheumatoid arthritis, and neurodegenerative diseases. Although it cannot be
      measured directly in biological systems, several biomarkers have been identified
      that provide a measure of oxidative damage to biomolecules. These include amino
      acid oxidation products (methionine sulfoxide, ortho-tyrosine (o-tyr) and
      dityrosine, chlorotyrosine and nitrotyrosine), as well as chemical modifications
      of protein following carbohydrate or lipid oxidation, such as N epsilon
      (carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, and malondialdehyde and
      4-hydroxynonenal adducts to amino acids. Other biomarkers include the amino acid
      cross-link pentosidine, the imidazolone adducts formed by reaction of 3
      deoxyglucosone or methylglyoxal with arginine, and the imidazolium cross-links
      formed by the reaction of glyoxal and methylglyoxal with lysine residues in
      protein. These compounds have been measured in short-lived intracellular
      proteins, plasma proteins, long-lived extracellular proteins, and in urine,
      making them valuable tools for monitoring tissue-specific and systemic chemical
      and oxidative damage to proteins in biological systems. They are normally
      measured by sensitive high-performance liquid chromatography or gas
      chromatography-mass spectrometry methods, requiring both complex analytical
      instrumentation and derivatization procedures. However, sensitive
      immunohistochemical and ELISA assays are now available for many of these
      biomarkers. Immunochemical assays should facilitate studies on the role of
      oxidative stress in aging and chronic disease and simplify the evaluation of
      therapeutic approaches for limiting oxidative damage in tissues and treating
      pathologies associated with aging and disease. In this article we summarize
      recent data and conclusions based on immunohistochemical and ELISA assays,
      emphasizing the strengths and limitations of the techniques.

PMID- 9928438
TI  - Assessing the effects of deprenyl on longevity and antioxidant defenses in
      different animal models.
AB  - Among many pharmaceuticals that have been tested for their effects on longevities
      of different animal rodents, deprenyl is unique in that its effects on longevity
      has been tested in at least four different animal species by independent research
      groups and that the effect has been postulated to be due to its effect of raising
      such antioxidant enzyme activities as superoxide dismutase (SOD) and catalase
      (CAT) in selective brain regions. Thus far, in all four species of animals
      examined (rats, mice, hamsters, and dogs), a positive effect was demonstrated,
      although the extent of its effect is quite variable. Our group has examined the
      effect on longevities in rats and mice and on antioxidant enzymes in rats, mice,
      and dogs. Although in rats of both sexes, we have obtained positive effects on
      longevity, two studies with different doses in mice did not reveal a
      significantly positive effect. We have observed, however, significantly positive
      effects on SOD (in Cu, Zn-, and Mn-) as well as CAT (but not glutathione
      peroxidase) activities in the brain dopaminergic system such as in the S. nigra
      and striatum (but not in hippocampus) in all rats, mice, and dogs, although the
      effects were quite variable, depending on the doses used. In mice, however, a
      long-term administration (3x/w, 3 months) caused a remarkable decrease in the
      magnitude of activity as well as a narrowing of the effective dose range, which
      may explain a relatively weak effect of the drug on mouse longevity. Further, a
      recent study on aging beagle dogs by Ruehl et al. showed a remarkable effect on
      longevity, which agrees with our SOD study in dogs. Although deprenyl has been
      claimed to have several other effects, such as a radical scavenging effect and a
      neuroprotective effect, past reports on its effects on longevities and
      antioxidant defenses are compatible with the notion that the drug prolongs the
      life span of animals by reducing the oxidative damage to the brain dopaminergic
      system during aging. Further, our studies on F-344 rats as well as a dog study by
      Ruehl et al. suggest that the drug may at least partially prolong the life span
      of animals by enhancing immune system function and preventing tumor development
      in animals.

PMID- 9928439
TI  - Age-associated memory impairment. Assessing the role of nitric oxide.
AB  - Several neurotransmitter systems have been investigated to assess hypothesized
      mechanisms underlying the decline in recent memory abilities in normal aging and
      in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T
      maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N
      methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze
      learning is impaired by antagonists to mACh or NMDA receptors. We have also shown
      that stimulation of mACh receptors can overcome a maze learning deficit induced
      by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar
      blockade of mACh receptors. No consistent evidence in rats has been produced from
      our laboratory to reveal significant age-related declines in mACh or NMDA
      receptor binding in the hippocampus (HC), a brain region that is greatly involved
      in processing of recent memory. Thus, we have directed attention to the
      possibility of a common signal transduction pathway, the nitric oxide (NO)
      system. Activated by calcium influx through the NMDA receptor, NO is hypothesized
      to be a retrograde messenger that enhances presynaptic Glu release. Maze learning
      can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase
      (NOS), or enhanced by stimulating NO release. However, we have found no age
      related loss of NOS-containing HC neurons or fibers in rats. Additionally, other
      laboratories have reported no evidence of an age-related loss of HC NOS activity.
      In a microdialysis study we have found preliminary evidence of reduced NO
      production following NMDA stimulation. We are currently working to identify the
      parameters of this phenomenon as well as testing various strategies for safely
      stimulating the NO system to improve memory function in aged rats.

PMID- 9928440
TI  - Telomeres: influencing the rate of aging.
AB  - Evidence is reviewed that suggests a central role for telomeres in one major
      model of biological aging, namely, proliferative senescence. Telomeric shortening
      with each cell division does not only act as a biological clock, but appears to
      trigger the ultimate loss of proliferative ability via activation of the p53
      dependent check point system. Oxidative stress induces single-stranded damage in
      telomeric DNA. It is not clear yet whether this damage occurs in the form of
      single-stranded gaps or overhangs or as arbitrarily distributed single-stranded
      breaks. However, in contradiction to the rest of the genome, this damage is not
      repaired in telomeres. It is, therefore, the major cause of telomere shortening
      even under standard in vitro cell culture conditions. Therefore, controlling the
      oxidative load onto DNA, in general, and, especially, onto telomeres might become
      a major factor to influence the rate of aging. Further experiments demonstrate
      that G-rich single-stranded telomeric DNA fragments do activate the p53 check
      point control, leading to an inhibition of proliferation in wild-type p53 cells.
      Not only the shortening of telomeres down to a "signal value," but accumulation
      of telomeric single-stranded DNA fragments, as well, could be relevant triggers
      for proliferative senescence.

PMID- 9928441
TI  - Redox regulation of the caspases during apoptosis.
AB  - Apoptosis is now widely recognized as being a distinct process of importance both
      in normal physiology and pathology. In the current paradigm for apoptotic cell
      death, the activity of a family of proteases, caspases, related to interleukin-1
      beta-converting enzyme (ICE) orchestrates the multiple downstream events, such as
      cell shrinkage, membrane blebbing, glutathione (GSH) efflux, and chromatin
      degradation that constitute apoptosis. Recent studies suggest that mitochondria
      could be the principle sensor and that the release of mitochondrial factors, such
      as cytochrome c, is the critical event governing the fate of the cell.--One of
      the most reproducible inducers of apoptosis is mild oxidative stress, although it
      is unclear how an oxidative stimulus can activate the caspase cascade. Oxidative
      modification of proteins and lipids has also been observed in cells undergoing
      apoptosis in response to nonoxidative stimuli, suggesting that intracellular
      oxidation may be a general feature of the effector phase of apoptosis. The
      caspases themselves are cysteine-dependent enzymes and, as such, appear to be
      redox sensitive. Indeed, our recent work on hydrogen peroxide-mediated apoptosis
      suggests that prolonged or excessive oxidative stress can actually prevent
      caspase activation. A physiological example of this is the NADPH oxidase-derived
      oxidants generated by stimulated neutrophils that prevent caspase activation in
      these cells. Pursuant to these findings, stimulated neutrophils appear to use a
      specialized caspase-independent pathway to initiate phosphatidylserine (PS)
      exposure and subsequent phagocytic clearance. The possible implications of these
      dual roles for reactive oxygen species in apoptosis, that is, induction and
      inhibition of caspases, are discussed in the present review.

PMID- 9928442
TI  - Nutrition, osteoporosis, and aging.
AB  - Loss of bone is an almost universal accompaniment of aging that proceeds at an
      average rate of 0.5-1% per annum from midlife onwards. There are at least four
      nutrients involved in this process: calcium, salt, protein, and vitamin D, at
      least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium
      is a positive risk factor because calcium requirement rises at the menopause due
      to an increase in obligatory calcium loss and a small reduction in calcium
      absorption that persist to the end of life. A metaanalysis of 20 calcium trials
      shows that this process can generally be arrested by calcium supplementation,
      although there is some doubt about its effectiveness in the first few years after
      menopause. Salt is a negative risk factor because it increases obligatory calcium
      loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body.
      Restricting salt intake lowers the rate of bone resorption in postmenopausal
      women. Protein is another negative risk factor; increasing animal protein intake
      from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein
      intakes in third world countries may partially protect against osteoporosis.
      Vitamin D (sometimes called a nutrient and sometimes a hormone) is important
      because age-related vitamin D deficiency leads to malabsorption of calcium,
      accelerated bone loss, and increased risk of hip fracture. Vitamin D
      supplementation has been shown to retard bone loss and reduce hip fracture
      incidence in elderly women.

PMID- 9928443
TI  - The effect of long-term dietary supplementation with antioxidants.
AB  - The impact of diet and specific food groups on aging and age-associated
      degenerative diseases has been widely recognized in recent years. The modern
      concept of the free radical theory of aging takes as its basis a shift in the
      antioxidant/prooxidant balance that leads to increased oxidative stress,
      dysregulation of cellular function, and aging. In the context of this theory,
      antioxidants can influence the primary "intrinsic" aging process as well as
      several secondary age-associated pathological processes. For the latter, several
      epidemiological and clinical studies have revealed potential roles for dietary
      antioxidants in the age-associated decline of immune function and the reduction
      of risk of morbidity and mortality from cancer and heart disease. We reported
      that long-term supplementation with vitamin E enhances immune function in aged
      animals and elderly subjects. We have also found that the beneficial effect of
      vitamin E in the reduction of risk of atherosclerosis is, in part, associated
      with molecular modulation of the interaction of immune and endothelial cells.
      Even though the effects of dietary antioxidants on aging have been mostly
      observed in relation to age-associated diseases, the effects cannot be totally
      separated from those related to the intrinsic aging process. For modulation of
      the aging process by antioxidants, earlier reports have indicated that
      antioxidant feeding increased the median life span of mice to some extent. To
      further delineate the effect of dietary antioxidants on aging and longevity,
      middle-aged (18 mo) C57BL/6NIA male mice were fed ad libitum semisynthetic AIN-76
      diets supplemented with different antioxidants (vitamin E, glutathione,
      melatonin, and strawberry extract). We found that dietary antioxidants had no
      effect on the pathological outcome or on mean and maximum life span of the mice,
      which was observed despite the reduced level of lipid peroxidation products, 4
      hydroxynonenol, in the liver of animals supplemented with vitamin E and
      strawberry extract (1.34 +/- 0.4 and 1.6 +/- 0.5 nmol/g, respectively) compared
      to animals fed the control diet (2.35 +/- 1.4 nmol/g). However, vitamin E
      supplemented mice had significantly lower lung viral levels following influenza
      infection, a viral challenge associated with oxidative stress. These and other
      observations indicate that, at present, the effects of dietary antioxidants are
      mainly demonstrated in connection with age-associated diseases in which oxidative
      stress appears to be intimately involved. Further studies are needed to determine
      the effect of antioxidant supplementation on longevity in the context of moderate
      caloric restriction.

PMID- 9928444
TI  - B vitamins and homocysteine in cardiovascular disease and aging.
AB  - The sulfur-containing amino acid, homocysteine, is formed from the essential
      amino acid methionine, and a number of B vitamins are involved in methionine
      metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta
      synthase, which mediates the transformation of homocysteine to cystathionine, the
      initial step in the transsulfuration pathway and the urinary excretion of sulfur.
      In a normal diet there is conservation of the carbon skeleton, and about 50% of
      the homocysteine formed is remethylated to methionine via steps that require
      folic acid and vitamin B12. A deficiency of any of these three vitamins leads to
      modest homocyst(e)ine elevation, as does diminished renal function, both of which
      are common in the elderly. It is also established that homocyst(e)ine elevation
      of this order is associated with increased cardiovascular risk but is also
      associated with most established risk factors, although it is thought to be an
      independent contributor. In the inborn error of metabolism homocystinuria due to
      cystathionine beta synthase deficiency there is greatly increased circulating
      homocyst(e)ine and a clear association with precocious vascular disease. In about
      50% of these patients there is a vascular event before the age of 30 years. The
      homocysteine-induced adverse vascular changes appear to result from endothelial
      and smooth muscle cell effects and increased thrombogenesis. We have documented a
      highly significant reduction in the occurrence of vascular events during 539
      patient years of treatment in 32 patients with cystathionine beta synthase
      deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine
      lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine
      nonresponsive patients also received oral betaine. Although a cause and effect
      relationship is postulated for the increased cardiovascular risk associated with
      mild homocysteine elevation, a common cause of this elevation is the
      methylenetetrahydrofolate reductase C677T mutation. Homozygotes occur in about
      11% of Caucasian populations. However, the mutation is not associated with
      increased coronary risk. Since mild homocysteine elevation is easily normalized
      by B vitamin supplementation, usually with folic acid, it remains for controlled
      clinical trials of this inexpensive therapy to determine whether normalizing mild
      homocyst(e)ine elevation reduces cardiovascular risk.

PMID- 9928445
TI  - Nutrition, cancer, and aging.
AB  - The parallel increase in cancer risk with advancing age is well recognized, and
      several pathophysiological mechanisms common to both conditions have been
      proposed to explain this interrelationship. The importance of nutrition, both in
      delaying the aging process and in protecting against cancer is also well
      recognized, and it is therefore of interest to compare the relative impact
      several of the more widely studied dietary manipulations may have on each of
      these conditions. For example, caloric restriction, which putatively reduce
      oxidative stress and effectively increases life span in animals also seems to
      reduce the incidence of many cancers, possibly due to diminished mitogenesis.
      Likewise, oxidative damage to DNA appears to be common to both processes but may
      be more important in the mitochondria with respect to aging and in the nucleus in
      relation to cancer. Inadequate dietary folate and impaired DNA methylation status
      are closely associated with increased cancer risk, and recently defective somatic
      cell methylation and accumulated genetic instability have been proposed as key
      mechanisms contributing to senescence. Several other well-established anticancer
      dietary strategies, which include increased fiber intake and the consumption of
      more fruits and vegetables, have not been studied extensively in relation to
      aging, although many of the phytochemicals considered important as
      chemopreventive agents for cancer may well contribute to delaying the aging
      process. Although not directly related to nutrition, but nevertheless highly
      relevant, is the question of physical activity, which has been strongly linked to
      a reduction in risk of some cancers. Although less is known with respect to
      exercise and biological markers of aging, physical activity does appear to retard
      the age-related decline in the muscle strength and in the bone density.

PMID- 9928446
TI  - Combined exercise and dietary intervention to optimize body composition in aging.
AB  - Concomitant losses of skeletal muscle and bone mass along with gradual accretion
      of adipose tissue typify usual human aging. Recent investigations have attempted
      to modify these processes with various combinations of dietary and exercise
      intervention in older adults. Complete nutritional supplements given with weight
      lifting exercise have been shown to augment muscle and fat gains in healthy older
      men, but have merely suppressed habitual dietary intake when administered to
      frail sedentary elders, and have not altered body composition responses to
      strength training in this population. Protein supplementation at twice the RDA
      does not improve skeletal muscle function or increase muscle mass in healthy
      elderly weight lifters compared to those on a normal diet. Calcium
      supplementation during one year of aerobic training has an independent beneficial
      effect on cortical bone density at the femoral neck in postmenopausal women,
      whereas the exercise is associated with trabecular bone increases in the lumbar
      vertebrae. Hypocaloric dieting, with or without aerobic exercise, results in
      losses of weight, fat and lean mass in obese elderly men and women. By contrast,
      resistance training during hypocaloric dieting augments lean mass while further
      reducing fat mass. Low protein, isoenergetic diets result in muscle atrophy in
      older women. Current studies will determine the ability of resistance training to
      offset these catabolic effects on skeletal muscles of a low-protein (0.6
      g/kg/day) diet prescribed for elderly with chronic renal failure. More long-term
      studies of efficacy and feasibility of diet and exercise combinations are needed
      in the aged to optimize the potential for healthful shifts in body composition.

PMID- 9928447
TI  - The biochemical, pathophysiological, and medical aspects of ubiquinone function.
AB  - Ubiquinone (Q) shares its biological implication in membrane-associated redox
      reactions with a variety of other redox carriers, such as dehydrogenases, non
      heme-iron proteins, and cytochromes. Peculiarities arise from the lack of
      transition metals, which in contrast to the other electron carriers do not
      participate in redox-shuttle activities of Q. Another peculiarity is the
      lipophilicity of Q, which allows free movement between reductants and oxidants of
      a membrane. The chemistry of Q reduction and ubiquinol oxidation requires the
      stepwise acceptance and transfer of two single electrons associated with the
      addition or release of two single H+. These special qualities are widely used in
      biological membranes for linear electron transfer and transmembranous H+
      translocation. In mitochondria it was long reported that under certain conditions
      linear e- transfer from the semireduced form (SQ.) to native oxidants of the
      respiratory chain may run out of control, thereby establishing a permanent source
      of oxygen radical release. It should be mentioned that in mitochondria e-
      transfer to dioxygen out of sequence requires a particular treatment with
      inhibitors and uncouplers of the respiratory chain. Nevertheless, it is generally
      assumed that Q is mainly involved in mitochondrial O2.- generation and that
      mitochondria represent the major source of O2.- radicals under physiological and
      various pathophysiological conditions. The ever-increasing application of
      coenzyme Q as an antioxidant for the prophylaxis and treatment of a great variety
      of functional disorders, including senescence, has considerably stimulated our
      interest in the potential prooxidative potency of this natural electron carrier.
      Experimental evidence will be presented that under physiological conditions Q
      implicated in mitochondrial e- transfer of the respiratory chain is not involved
      in cellular oxygen activation. It will also be shown that alterations of Q from
      an e- carrier to an active radical promotor is possible under various conditions.
      In addition, reaction products emerging from the antioxidant activity of
      ubiquinol were found to stimulate the formation of inorganic as well as organic
      oxygen radicals.

PMID- 9928448
TI  - Reactive oxygen intermediates, molecular damage, and aging. Relation to
      melatonin.
AB  - Melatonin, the chief secretory product of the pineal gland, is a direct free
      radical scavenger and indirect antioxidant. In terms of its scavenging activity,
      melatonin has been shown to quench the hydroxyl radical, superoxide anion
      radical, singlet oxygen, peroxyl radical, and the peroxynitrite anion.
      Additionally, melatonin's antioxidant actions probably derive from its
      stimulatory effect on superoxide dismutase, glutathione peroxidase, glutathione
      reductase, and glucose-6-phosphate dehydrogenase and its inhibitory action on
      nitric oxide synthase. Finally, melatonin acts to stabilize cell membranes,
      thereby making them more resistant to oxidative attack. Melatonin is devoid of
      prooxidant actions. In models of oxidative stress, melatonin has been shown to
      resist lipid peroxidation induced by paraquat, lipopolysaccharide, ischemia
      reperfusion, L-cysteine, potassium cyanide, cadmium chloride, glutathione
      depletion, alloxan, and alcohol ingestion. Likewise, free radical damage to DNA
      induced by ionizing radiation, the chemical carcinogen safrole,
      lipopolysaccharide, and kainic acid are inhibited by melatonin. These findings
      illustrate that melatonin, due to its high lipid solubility and modest aqueous
      solubility, is able to protect macromolecules in all parts of the cell from
      oxidative damage. Melatonin also prevents the inhibitory action of ruthenium red
      at the level of the mitochondria, thereby promoting ATP production. In humans,
      the total antioxidative capacity of serum is related to melatonin levels. Thus,
      the reduction in melatonin with age may be a factor in increased oxidative damage
      in the elderly.

PMID- 9928449
TI  - Recycling and redox cycling of phenolic antioxidants.
AB  - Effectiveness of phenolic antioxidants in protecting against oxidative stress
      depends on their reactivity towards reactive oxygen species and the reactivity of
      the antioxidant phenoxyl radicals towards critical biomolecules. Reduction of
      phenoxyl radicals by intracellular reductant (ascorbate, thiols) as well as by
      enzymes or intermediates of electron transport (e.g., in mitochondria and the
      endoplasmic reticulum) recycles phenolic antioxidants, thus enhancing antioxidant
      protection. Several cascades may be involved in physiologically relevant
      recycling of vitamin E from its phenoxyl radicals. The two major ones are
      dihydrolipoic acid-->(GSH)-->ascorbate, and enzymes of electron transport-
      >coenzyme Q. Importantly, phenoxyl radicals of vitamin E are not directly reduced
      by intracellular thiols. By contrast, a number of natural phenolic compounds that
      act as very effective scavengers of reactive oxygen species and organic radicals,
      may generate reactive secondary radicals of antioxidants. These secondary
      radicals react and modify critical intracellular targets (lipids, proteins, and
      DNA). As a result, the role of these phenolic compounds as biological
      antioxidants may be limited because of their ability to cause cyto- and genotoxic
      effects. Typical examples are some estrogens and phenolic drugs (e.g., the
      antitumor drug, etoposide) that can protect lipids but oxidize GSH and protein
      sulfhydryls. Moreover, phenoxyl radicals produced in the course of radical
      scavenging by some phenolic compounds (e.g., phenol) are capable of oxidizing
      both proteins and lipids. Hence, reactivity of phenoxyl radicals should be
      considered as a critical factor in the development of new antioxidant
      protectants.

PMID- 9928450
TI  - The chemistry and biological effects of flavonoids and phenolic acids.
AB  - Flavonoids and phenolic acids are widely distributed in higher plants and form
      part of the human diet. Recent interest in these substances has been stimulated
      by the potential health benefits arising from the antioxidant activity of these
      polyphenolic compounds. This review outlines the basic chemistry, biosynthesis,
      and structure-activity relationships of these compounds with respect to their
      antioxidant activity. Although there is considerable in vitro evidence
      establishing antioxidant activity for polyphenolics found in the diet, there are
      few studies in humans on the absorption and bioavailability of these compounds.
      The possible in vivo antioxidant effects of the flavonoids is even less well
      understood. For example, controlled human intervention studies with beverages,
      such as red wine, that are rich in polyphenolic compounds, have yielded
      conflicting results. Our own work and that of others suggests that the final
      effects of such beverages may be a balance between the well-described prooxidant
      effects of alcohol and its metabolism and the antioxidant effects of the
      polyphenolic constituents. There is a need for further studies to increase our
      understanding of the absorption and in vivo biological effects of this family of
      compounds.

PMID- 9928451
TI  - The antioxidant and biological properties of the carotenoids.
AB  - Much effort has been expended in evaluating the relative antioxidant potency of
      carotenoid pigments in both in vitro and in vivo experiments. It is quite clear
      that in vitro, carotenoids can inhibit the propagation of radical-initiated lipid
      peroxidation, and thus fulfill the definition of antioxidants. When it comes to
      in vivo systems, it has been much more difficult to obtain solid experimental
      evidence that carotenoids are acting directly as biological antioxidants. In
      fact, under nonphysiological circumstances, carotenoids may act as prooxidants.
      These results can be modified by altering the oxidant stress, the cellular or
      subcellular system, the type of animal, and environmental conditions, such as
      oxygen tension. Results of this type raise the question as to whether it is still
      appropriate to group the carotenoids with such antioxidant vitamins as vitamin E
      and vitamin C. Thus, the biological properties of the carotenoids may be much
      more related to the products of the interaction of carotenoids with oxidant
      stress, that is, such breakdown products as apocarotenoids and retinoids.

PMID- 9928452
TI  - Structural and functional changes in proteins induced by free radical-mediated
      oxidative stress and protective action of the antioxidants N-tert-butyl-alpha
      phenylnitrone and vitamin E.
AB  - The free radical theory of aging proposes that reactive oxygen species (ROS)
      cause oxidative damage over the lifetime of the subject. It is the cumulative and
      potentially increasing amount of accumulated damage that accounts for the
      dysfunctions and pathologies seen in normal aging. We have previously
      demonstrated that both normal rodent brain aging and normal human brain aging are
      associated with an increase in oxidative modification of proteins and in changes
      in plasma membrane lipids. Several lines of investigation indicate that one of
      the likely sources of ROS is the mitochondria. There is an increase in oxidative
      damage to the mitochondrial genome in aging and a decreased expression of
      mitochondrial mRNA in aging. We have used a multidisciplinary approach to the
      characterization of the changes that occur in aging and in the modeling of brain
      aging, both in vitro and in vivo. Exposure of rodents to acute normobaric
      hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins
      and loss of activity for the oxidation-sensitive enzymes glutamine synthetase and
      creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal
      membrane protein oxidation following hyperoxia. These changes are similar to the
      changes seen in senescent brains, compared to young adult controls. The
      antioxidant spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) was
      effective in preventing all of these changes. In a related study, we
      characterized the changes in brain protein spin labeling and cytosolic enzyme
      activity in a series of phenotypically selected senescence-accelerated mice
      (SAMP), compared to a resistant line (SAMR1) that was derived from the same
      original parents. In general, the SAM mice demonstrated greater oxidative changes
      in brain proteins. In a sequel study, a group of mice from the SAMP8-sensitive
      line were compared to the SAMR1-resistant mice following 14 days of daily PBN
      treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the
      cytoskeletal protein labeling toward that of the normal control line (SAMR1). The
      results of these and related studies indicate that the changes in brain function
      seen in several different studies may be related to the progressive oxidation of
      critical brain proteins and lipids. These components may be critical targets for
      the beneficial effects of gerontotherapeutics both in normal aging and in disease
      of aging.

PMID- 9928453
TI  - How best to ensure daily intake of antioxidants (from the diet and supplements)
      that is optimal for life span, disease, and general health.

PMID- 9928455
TI  - Total extent and cellular distribution of mitochondrial DNA mutations in aging.

PMID- 9928458
TI  - Adolescent growth, development, and psychosocial aspects of sports participation:
      an overview.
AB  - This chapter examines sports participation in the context of adolescent growth
      and development. Because the nature of sports participation is highly organized
      and competitive, it is imperative that parents, coaches, physicians, and other
      clinicians remember that they may be placing increased pressures on the
      adolescent to perform and practice. The authors review the impact of physical
      growth and psychosocial development and also describe how substance abuse,
      depression, and aggressive behavior may or may not be influenced by sports
      participation.

PMID- 9928459
TI  - Cardiovascular evaluation of the young athlete.
AB  - Young athletes with possible cardiac problems may require medical advice, sports
      medicine information, and treatment before a clinician can sanction sports
      participation. In addition, the potential medical liability of cardiac
      abnormalities makes the preparticipation cardiac evaluation a top priority. The
      author emphasizes the importance of obtaining a thorough cardiac history and
      performing a cardiac-specific physical examination, which may include diagnostic
      tests such as the treadmill and color flow Doppler echocardiography. Common
      cardiac referral complaints such as chest pain, murmurs, and syncope are also
      reviewed.

PMID- 9928460
TI  - Diabetes mellitus and sports.
AB  - The adolescent with insulin-dependent diabetes mellitus (IDDM) can safely
      participate in sports activities without interference from the disease. To ensure
      safe and successful participation, clinicians must appreciate how diabetes may
      alter the physiologic adaptation to strenuous exercise and how an individualized
      self-care plan can empower the adolescent with IDDM to effectively manage meal
      planning, blood glucose testing, and insulin injections. Various types of
      insulin, insulin schedules, and insulin delivery devices that may suit a wide
      variety of training and activity regimens are described.

PMID- 9928461
TI  - Exercise and sports in the adolescent with chronic pulmonary disease.
AB  - Every young person with a respiratory disability should be given the opportunity
      to maximize his or her exercise potential. Conditions such as asthma, affecting
      some 14 to 15 million people and cystic fibrosis (CF), affecting about 30,000
      people in the U.S., may exclude young people from sports participation. And yet
      regular aerobic exercise and weight training have been shown to provide
      significant psychological and physical benefits to people with lung disease and
      diseases of the respiratory muscles and chest wall. The authors document the
      effects of asthma, CF, and neuromuscular diseases on aerobic exercise to prevent
      unnecessary limitations on participation due to inaccurate preconceived notions
      of sports of exercise capacity in chronically ill adolescents.

PMID- 9928462
TI  - Tobacco, youth, and sports.
AB  - Cigarette smoking constitutes the single largest threat to the health and
      longevity of American youth. Each year, almost 400,000 people die prematurely
      from tobacco-related diseases. Moreover, 90% of adult smokers began using tobacco
      before their eighteenth birthday, and each day 3,000 children and adolescents
      begin smoking. Smokeless tobacco use is less prevalent than cigarette smoking but
      has similar deleterious health effects and is often also glamorized by sports
      figures. This article examines the relationship between tobacco and sports and
      offers specific steps that physicians (specifically orthopedic surgeons and
      sports medicine physicians, who interact with athletes at sporting events and in
      schools as well as at the clinic) can take to help prevent or minimize tobacco
      use. Although sports have been used by the tobacco industry to promote tobacco
      products to young people, the authors suggest new ways to prevent its success.

PMID- 9928463
TI  - The physically challenged athlete.
AB  - Several studies note that the relative risk of injury for physically challenged
      athletes is approximately the same as that of nondisabled athletes. Since the
      1940s physically challenged athletes have increasingly competed on national and
      international levels. This chapter describes sport-specific adaptations (such as
      a prosthesis or wheelchair), classifies the suitability of sports activities
      according to disability, and outlines measures to prevent injury in disabled
      athletes. The author also includes a resource list of publications,
      organizations, and web sites for disabled athletes.

PMID- 9928464
TI  - Nutritional supplements: fact vs. fiction.
AB  - An athlete may think that if a small amount of a chemical helps his or her
      performance, more will work better. The most appealing supplements are those that
      claim to help build muscle, improve endurance, and reduce body fat. Widespread
      acceptance of herbal of "natural" alternatives to mainstream medicine (especially
      nutritional supplements) is increasing, and the market is largely unregulated.
      The authors summarize the facts and fiction surrounding the use of popular
      products that may be found at the pharmacy and health food store that are being
      used in the locker rooms of high schools, colleges, and gyms in the U.S. They
      urge clinicians to stress the value of a well balanced diet to their active
      adolescent patients and not to encourage supplement use.

PMID- 9928465
TI  - Conditions of the spine.
AB  - Sequelae of congenital, developmental, infectious, degenerative, and neoplastic
      processes present themselves throughout adolescence, a time of rapid growth and
      spinal development. The author outlines the elements of an accurate diagnostic
      physical examination, the signs and symptoms of various spinal deformities, and
      their diagnosis and treatment. The potential causes of back pain in children and
      adolescents are explored. The author cautions against dismissing complaints of
      back pain in the skeletally immature population as mere "growing pains."

PMID- 9928466
TI  - The breast and sports: issues for the clinician.
AB  - Although a number of recent reviews have focused on the effects of exercise and
      sports on menstrual function, minimal emphasis has been placed on how the breast
      is affected. Increasing numbers of female athletes are participating in
      previously male-dominated contact sports; the effect on overall breast health
      from medium-to-high impact activities remains to be seen. This article reviews
      the basic anatomy and embryology of breast tissue, outlines various problems of
      the breast that the adolescent athlete may encounter, and offers management
      strategies for such problems.

PMID- 9928467
TI  - Hip, pelvic, and thigh injuries and disorders in the adolescent athlete.
AB  - The common injuries and disorders that affect the hip joint, pelvis, and thigh
      and its surrounding tissues are discussed in this chapter. The clinician's
      challenge is to determine the severity of the injury and select the correct
      treatment and rehabilitation. Careful observation, diagnostic tests, and a
      thorough medical history aids this selection. The characteristics of several
      sports injuries are highlighted with the essential components of effective
      treatment and physical rehabilitation.

PMID- 9928468
TI  - Shoulder and elbow injuries and painful syndromes.
AB  - Childhood participation in organized sports has led to increased incidence of
      orthopedic complaints in the pediatric and adolescent populations, and year-round
      participation in a single sport allows no rest period from muscle use, bone
      development, and maturation. What effect do these factors have on the
      musculoskeletal system of the young athlete? They may lead to injuries such as
      dislocations, fractures, and problems of bone growth. This comprehensive review
      of shoulder and elbow anatomy and mechanisms of injury includes specific
      recommendations for rehabilitation.

PMID- 9928469
TI  - Knee disorders and injuries in adolescents.
AB  - The range of knee injuries that adolescent athletes may sustain include minimal
      injury to the knee, such as contusions and mild sprains, and more serious
      mechanical disruptions that may lead to permanent disability if not properly
      treated. The author identifies injury patterns that may be seen by the clinician
      and offers guidelines on diagnosis and treatment.

PMID- 9928470
TI  - Foot and ankle injuries and disorders.
AB  - This chapter analyses the mechanics of walking and running gait and delineates
      the terminology used to describe foot and ankle injuries. A helpful anatomic
      review precedes explanations of the mechanisms of sports injuries in this area.
      The author documents the correct diagnoses and treatments for foot and ankle
      sprains, fractures, and stress injuries.

PMID- 9928471
TI  - Injuries to the hand and wrist.
AB  - Because sports-related injuries to the hand and wrist are relatively frequent and
      lead to significant disability if misdiagnosed or improperly treated, it is
      important to identify the specific nature of such an injury to reach an accurate
      diagnosis and administer appropriate treatment. The author advocates an initial
      three-step process that may help the clinician to effectively diagnose and treat
      injuries: listen to the description of injury mechanisms; observe the site of
      injury; palpate the area for tenderness or instability.

PMID- 9928472
TI  - Alfred D. Hershey.

PMID- 9928474
TI  - Regulation of symbiotic root nodule development.
AB  - Symbiosis between rhizobia and leguminous plants leads to the formation of N2
      fixing root nodules. The interaction of rhizobia and plants shows a high degree
      of host specificity based on the exchange of chemical signals between the
      symbiotic partners. The plant signals, flavonoids exuded by the roots, activate
      the expression of nodulation genes, resulting in the production of the rhizobial
      lipochitooligosaccharide signals (Nod factors). Nod factors act as morphogens
      that, under conditions of nitrogen limitation, induce cells within the root
      cortex to divide and to develop into nodule primordia. This review focuses on how
      the production of Nod factors is regulated, how these signals are perceived and
      transduced by the plant root, and the physiological conditions and plant factors
      that control the early events leading to root nodule development.

PMID- 9928473
TI  - The role of the FHIT/FRA3B locus in cancer.
AB  - Common fragile sites form gaps at characteristic chromosome bands in metaphases
      from normal cells after aphidicolin induction. The distribution of common fragile
      sites parallels the positions of neoplasia-associated chromosomal rearrangements,
      prompting the proposal that fragility disposes to chromosomal rearrangements.
      Implicit in this hypothesis is that genes at fragile sites are altered by
      chromosome rearrangement and thus contribute to neoplastic growth. Chromosome
      band 3p14.2, encompassing the most inducible common fragile region, FRA3B, has
      been cloned and the FHIT gene, straddling FRA3B, characterized. The gene is
      inactivated by deletions in cancer-derived cell lines and primary tumors and Fhit
      protein is absent or reduced in lung, stomach, kidney, and cervical carcinomas,
      consistent with function as a tumor suppressor. FRA3B thus fulfills the prophecy
      that fragile site alterations contribute to the neoplastic process through
      inactivation of a tumor suppressor gene.

PMID- 9928475
TI  - Targeting and assembly of periplasmic and outer-membrane proteins in Escherichia
      coli.
AB  - Escherichia coli must actively transport many of its proteins to extracytoplasmic
      compartments such as the periplasm and outer membrane. To perform this duty, E.
      coli employs a collection of Sec (secretion) proteins that catalyze the
      translocation of various polypeptides through the inner membrane. After
      translocation across the inner membrane, periplasmic and outer-membrane proteins
      are folded and targeted to their appropriate destinations. Here we review our
      knowledge of protein translocation across the inner membrane. We also discuss the
      various signal transduction systems that monitor extracytoplasmic protein folding
      and targeting, and we consider how these signal transduction systems may
      ultimately control these processes.

PMID- 9928476
TI  - The genetics of breast cancer susceptibility.
AB  - Following the genomic localization and subsequent identification of the breast
      cancer susceptibility genes, BRCA1 and BRCA2, the basic patterns of cancer risk
      associated with mutations in these genes have been defined. In addition,
      preliminary insights into the prevalence of mutations and their contributions to
      cancer incidence have been acquired. Features of breast and other cancers that
      develop in these genetic syndromes have now been investigated and shown to differ
      from sporadic versions of the same neoplasms. However, several areas are complex
      and require further clarification. There remain discrepancies between published
      cancer risk estimates. Furthermore, there may be variation in cancer risk between
      different mutations in the same gene and there is preliminary evidence that
      genetic and nongenetic influences may modify risks. Finally, it is probable that
      the genes underlying a substantial component of susceptibility to breast cancer
      remain to be identified.

PMID- 9928477
TI  - Nonsegmented negative-strand RNA viruses: genetics and manipulation of viral
      genomes.
AB  - Protocols to recover negative-stand RNA viruses entirely from cDNA have been
      established in recent years, opening up this virus group to the detailed analysis
      of molecular genetics and virus biology. The unique gene-expression strategy of
      nonsegmented negative-strand RNA viruses, which involves replication of
      ribonucleoprotein complexes and sequential synthesis of free mRNAs, has also
      allowed the use of these viruses to express heterologous sequences. There are
      advantages in terms of easy manipulation of constructs, high capacity for foreign
      sequences, genetically stable expression, and the possibility of adjusting
      expression levels. Fascinating prospects for biomedical applications and
      transient gene therapy are offered by chimeric virus vectors carrying novel
      envelope protein genes and targeted to defined host cells.

PMID- 9928478
TI  - The genetics of disulfide bond metabolism.
AB  - Disulfide bonds are required for the stability and function of a large number of
      proteins. Genetic analysis in combination with biochemical studies have
      elucidated the main catalysts involved in facilitating these processes in the
      cell. All enzymes involved in thiol-disulfide metabolism have a conserved active
      site that consists of two cysteine residues, separated by two intervening amino
      acids, the Cys-Xaa-Xaa-Cys motif. While these enzymes are capable of catalyzing
      both disulfide bond formation and reduction, they have evolved to perform one or
      the other reaction more efficiently. In the cytoplasm, multiple pathways are
      involved in the reduction of disulfide bonds that occur as part of the catalytic
      cycle of a variety of metabolic enzymes. In the bacterial periplasm, a system for
      the efficient introduction as well as isomerization of disulfide bonds is in
      place. In eukaryotes, disulfide bonds are introduced into proteins in the
      endoplasmic reticulum. Genetic studies have recently begun to reveal new features
      of this process. While the enzyme mechanisms of thiol-disulfide oxidoreductases
      have been the subject of much scrutiny, questions remain regarding where and when
      they act in vivo, their specificities, and the maintenance of the redox
      environment that determines their function.

PMID- 9928479
TI  - Comparative DNA analysis across diverse genomes.
AB  - We review concepts and methods for comparative analysis of complete genomes
      including assessments of genomic compositional contrasts based on dinucleotide
      and tetranucleotide relative abundance values, identifications of rare and
      frequent oligonucleotides, evaluations and interpretations of codon biases in
      several large prokaryotic genomes, and characterizations of compositional
      asymmetry between the two DNA strands in certain bacterial genomes. The
      discussion also covers means for identifying alien (e.g. laterally transferred)
      genes and detecting potential specialization islands in bacterial genomes.

PMID- 9928480
TI  - The ethylene gas signal transduction pathway: a molecular perspective.
AB  - The gaseous hormone ethylene induces diverse effects in plants throughout their
      life cycle. Ethylene response is regulated at multiple levels, from hormone
      synthesis and perception to signal transduction and transcriptional regulation.
      As more genes in the ethylene response pathway are cloned and characterized, they
      illustrate the precision with which signaling can be controlled. Wounding,
      pathogenic attack, flooding, fruit ripening, development, senescence, and
      ethylene treatment itself induce ethylene production. Ethylene binding to
      receptors with homology to two-component regulators triggers a kinase cascade
      that is propagated through the CTR1 Raf-like kinase and other components to the
      nucleus. Activation of the EIN3 family of nuclear proteins leads to induction of
      the relevant ethylene-responsive genes via other transcription factors, eliciting
      a response appropriate to the original stimulus.

PMID- 9928481
TI  - Molecular mechanisms of bacteriocin evolution.
AB  - Microorganisms are engaged in a never-ending arms race. One consequence of this
      intense competition is the diversity of antimicrobial compounds that most species
      of bacteria produce. Surprisingly, little attention has been paid to the
      evolution of such extraordinary diversity. One class of antimicrobials, the
      bacteriocins, has received increasing attention because of the high levels of
      bacteriocin diversity observed and the use of bacteriocins as preservatives in
      the food industry and as antibiotics in the human health industry. However,
      little effort has been focused on evolutionary questions, such as what are the
      phylogenetic relationships among these toxins, what mechanisms are involved in
      their evolution, and how do microorganisms respond to such an arsenal of weapons?
      The focus of this review is to provide a detailed picture of our current
      understanding of the molecular mechanisms involved in the process of bacteriocin
      diversification.

PMID- 9928482
TI  - Alternative splicing of pre-mRNA: developmental consequences and mechanisms of
      regulation.
AB  - Alternative splicing of pre-mRNAs is a powerful and versatile regulatory
      mechanism that can effect quantitative control of gene expression and functional
      diversification of proteins. It contributes to major developmental decisions and
      also to fine tuning of gene function. Genetic and biochemical approaches have
      identified cis-acting regulatory elements and trans-acting factors that control
      alternative splicing of specific pre-mRNAs. Both approaches are contributing to
      an understanding of their mode of action. Some alternative splicing decisions are
      controlled by specific factors whose expression is highly restricted during
      development, but others may be controlled by more modest variations in the levels
      of general factors acting cooperatively or antagonistically. Certain factors play
      active roles in both constitutive splicing and regulation of alternative
      splicing. Cooperative and antagonistic effects integrated at regulatory elements
      are likely to be important for specificity and for finely tuned differences in
      cell-type-specific alternative splicing patterns.

PMID- 9928483
TI  - Kinetochores and the checkpoint mechanism that monitors for defects in the
      chromosome segregation machinery.
AB  - Whether we consider the division of the simplest unicellular organisms into two
      daughter cells or the generation of haploid gametes by the most complex
      eukaryotes, no two processes secure the continuance of life more than the proper
      replication and segregation of the genetic material. The cell cycle, marked in
      part by the periodic rise and fall of cyclin-dependent kinase (CDK) activities,
      is the means by which these two processes are separated. DNA damage and mistakes
      in chromosome segregation are costly, so nature has further devised elaborate
      checkpoint mechanisms that halt cell cycle progression, allowing time for repairs
      or corrections. In this article, we review the mitotic checkpoint mechanism that
      responds to defects in the chromosome segregation machinery and arrests cells in
      mitosis prior to anaphase onset. At opposite ends of this pathway are the
      kinetochore, where many checkpoint proteins reside, and the anaphase-promoting
      complex (APC), the metaphase-to-interphase transition regulator. Throughout this
      review we focus on budding yeast but reference parallel processes found in other
      organisms.

PMID- 9928484
TI  - The diverse and dynamic structure of bacterial genomes.
AB  - Bacterial genome sizes, which range from 500 to 10,000 kbp, are within the
      current scope of operation of large-scale nucleotide sequence determination
      facilities. To date, 8 complete bacterial genomes have been sequenced, and at
      least 40 more will be completed in the near future. Such projects give
      wonderfully detailed information concerning the structure of the organism's genes
      and the overall organization of the sequenced genomes. It will be very important
      to put this incredible wealth of detail into a larger biological picture: How
      does this information apply to the genomes of related genera, related species, or
      even other individuals from the same species? Recent advances in pulsed-field gel
      electrophoretic technology have facilitated the construction of complete and
      accurate physical maps of bacterial chromosomes, and the many maps constructed in
      the past decade have revealed unexpected and substantial differences in genome
      size and organization even among closely related bacteria. This review focuses on
      this recently appreciated plasticity in structure of bacterial genomes, and
      diversity in genome size, replicon geometry, and chromosome number are discussed
      at inter- and intraspecies levels.

PMID- 9928485
TI  - Recombination and recombination-dependent DNA replication in bacteriophage T4.
AB  - General recombination is essential for growth of phage T4, because origin
      initiation of DNA replication is inactivated during development, and
      recombination-dependent initiation is necessary for continuing DNA replication.
      The requirement of recombination for T4 growth has apparently been a driving
      force to acquire and maintain multiple recombination mechanisms. This requirement
      makes this phage an excellent model to analyze several recombination mechanisms
      that appear redundant under optimal growth conditions but become essential under
      other conditions, or at different stages of the developmental program. The most
      important substrate for wild-type T4 recombination is single-stranded DNA
      generated by incomplete replication of natural or artificial chromosomal ends, or
      by nucleolytic degradation from induced breaks, or nicks. Recombination
      circumvents the further erosion of such ends. There are multiple proteins and
      multiple pathways to initiate formation of recombinants (by single-strand
      annealing or by strand invasion) and to convert recombinational intermediates
      into final recombinants ("cut and paste" or "cut and package"), or to initiate
      extensive DNA replication by "join-copy" or "join-cut-copy" mechanisms. Most T4
      recombination is asymmetrical, favoring the initiation of replication. In wild
      type T4 these pathways are integrated with physiological changes of other DNA
      transactions: mainly replication, transcription, and packaging. DNA replication
      and packaging enzymes participate in recombination, and recombination
      intermediates supply substrates for replication and packaging. The replicative
      recombination pathways are also important for transmission of intron DNA to
      intronless genomes ("homing"), and are implicated in horizontal transfer of
      foreign genes during evolution of the T-even phages. When horizontal transfer
      involves heteroduplex formation and repair, it is intrinsically mutagenic and
      contributes to generation of species barriers between phages.

PMID- 9928486
TI  - Natural selection at major histocompatibility complex loci of vertebrates.
AB  - The loci of the vertebrate major histocompatibility complex encode cell-surface
      glycoproteins that present peptides to T cells. Certain of these loci are highly
      polymorphic, and the mechanisms responsible for this polymorphism have been
      intensely debated. Four independent lines of evidence support the hypothesis that
      MHC polymorphisms are selectively maintained: (a) The distribution of allelic
      frequencies does not fit the neutral expectation. (b) The rate of nonsynonymous
      nucleotide substitution significantly exceeds the rate of synonymous substitution
      in the codons encoding the peptide-binding region of the molecule. (c)
      Polymorphisms have been maintained for long periods of time ("trans-species
      polymorphism"). (d) Introns have been homogenized relative to exons over
      evolutionary time, suggesting that balancing selection acts to maintain diversity
      in the latter, in contrast to the former.

PMID- 9928487
TI  - Evolution and mechanism of translation in chloroplasts.
AB  - The entire sequence (120-190 kb) of chloroplast genomes has been determined from
      a dozen plant species. The genome contains from 87 to 183 known genes, of which
      half encode components involved in translation. These include a complete set of
      rRNAs and about 30 tRNAs, which are likely to be sufficient to support
      translation in chloroplasts. RNA editing (mostly C to U base changes) occurs in
      some chloroplast transcripts, creating start and stop codons and changing codons
      to retain conserved amino acids. Many components that constitute the chloroplast
      translational machinery are similar to those of Escherichia coli, whereas only
      one third of the chloroplast mRNAs contain Shine-Dalgarno-like sequences at the
      correct positions. Analyses conducted in vivo and in vitro have revealed the
      existence of multiple mechanisms for translational initiation in chloroplasts.

PMID- 9928488
TI  - Alzheimer's disease: genetic studies and transgenic models.
AB  - Recent advances in a variety of areas of research, particularly in genetics and
      in transgenic (Tg)/gene targeting approaches, have had a substantial impact on
      our understanding of Alzheimer's disease (AD) and related disorders. After
      briefly reviewing the progress that has been made in diagnostic assessments of
      patients with senile dementia and in investigations of the neuropathology of AD,
      we discuss some of the genes/proteins that are causative or risk factors for this
      disease, including those encoding amyloid precursor protein, presenilin 1 and 2,
      and apolipoprotein E. In addition, we comment on several potential new candidate
      loci/genes. Subsequently, we review selected recent reports of analyses of a
      variety of lines of Tg mice that show several neuropathological features of AD,
      including A beta-amyloid deposits and dystrophic neurites. Finally, we discuss
      the several important issues in future investigations of Tg mice, with particular
      emphasis on the influences of genetic strains on phenotype, especially behavior,
      and strategies for making new models of neurodegenerative disorders. We believe
      that investigations of these Tg models will (a) enhance understanding of the
      relationships between impaired performance on memory tasks and the
      pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic
      mechanisms in vivo, (c) lead to identification of new therapeutic targets, and
      (d) allow testing of new treatment strategies first in mice and then, if
      successful, in humans with AD.

PMID- 9928490
TI  - Early patterning of the C. elegans embryo.
AB  - Studies of about 20 maternally expressed genes are providing an understanding of
      mechanisms of patterning and cell-fate determination in the early Caenorhabditis
      elegans embryo. The analyses have revealed that fates of the early blastomeres
      are specified by a combination of intrinsically asymmetric cell divisions and two
      types of cell-cell interactions: inductions and polarizing interactions. In this
      review we summarize the current level of understanding of the molecular
      mechanisms underlying these processes in the specification of cell fates in the
      pregastrulation embryo.

PMID- 9928489
TI  - The critical role of chromosome translocations in human leukemias.
AB  - Many chromosome abnormalities, especially translocations of inversions, are
      closely associated with a particular morphologic or phenotypic subtype of
      leukemia, lymphoma, or sarcoma. Cloning the genes at the breakpoints of these
      rearrangements has had a major impact on our understanding of the molecular
      biology of cancer. One such gene is MLL (myeloid-lymphoid or mixed lineage
      leukemia) located at chromosome band 11q23. The target gene(s) of MLL is unknown
      at present, but because of its homology to the trithorax gene in Drosophila as
      well as experimental data from mice, it appears to be involved in maintaining the
      function of some of the homeobox genes. Most genes involved in translocations
      have homologs in other organisms. Comparison of the functions of these genes in
      human cells with their function in other systems has enriched our understanding
      of their role in cell biology.

PMID- 9928492
TI  - Mating-type gene switching in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae can change its mating type as often as every generation
      by a highly choreographed, site-specific recombination event that replaces one
      MAT allele with different DNA sequences encoding the opposite allele. The study
      of this process has yielded important insights into the control of cell lineage,
      the silencing of gene expression, and the formation of heterochromatin, as well
      as the molecular events of double-strand break-induced recombination. In
      addition, MAT switching provides a remarkable example of a small locus control
      region--the Recombination Enhancer--that controls recombination along an entire
      chromosome arm.

PMID- 9928491
TI  - Genetic counseling: clinical and ethical challenges.
AB  - After explaining the origin, nature, and goals of genetic counseling, we consider
      the impact of the Human Genome Project on its practice. In light of the
      availability of presymptomatic tests for late-onset disorders and the possibility
      of preventive behavior or treatment, we examine the apparent conflict between
      nondirectiveness and directiveness in genetic counseling. We discuss views of
      genetic counselors, medical geneticists, and counselees on specific issues, and
      document gender differences in attitudes toward genetic ties to offspring.
      Because genetic discrimination and unequal access to genetic services are likely
      to increase with advances in genetics, we conclude that efforts of genetic
      counselors to adhere to the principle of justice or equity in their practice
      cannot be successful without governmental and public support, as well as support
      from researchers and colleagues in health care.

PMID- 9928493
TI  - Epitope tagging.
AB  - Epitope tagging is a recombinant DNA method by which a protein encoded by a
      cloned gene is made immunoreactive to a known antibody. This review discusses the
      major advantages and limitations of epitope tagging and describes a number of
      recent applications. Major areas of application include monitoring protein
      expression, localizing proteins at the cellular and subcellular levels, and
      protein purification, as well as the analysis of protein topology, dynamics and
      interactions. Recently the method has also found use in transgenic and gene
      therapy studies and in the emerging fields of functional genomics and proteomics.

PMID- 9928495
TI  - The spondylarthropathies: classification and diagnosis. Do we need new
      terminologies?
AB  - The present classification of a number of arthropathies linked to the B27 antigen
      under the term spondylarthropathy emphasises the frequent familial aggregation
      and clustering during follow-up of these diseases. This article is an attempt to
      review the progress elicited by the introduction of classification criteria for
      spondylarthropathy and the limitations of the concept. In particular, we address
      the continued need for better understanding of aetiology and pathogenesis. This
      makes it likely that we will need new classifications in the future and that this
      will evolve along with improvements in disease understanding. Working
      classifications that include the infectious triggers and features of the host
      response might be useful to guide new approaches.

PMID- 9928494
TI  - The leptotene-zygotene transition of meiosis.
AB  - The leptotene/zygotene transition of meiosis, as defined by classical cytological
      studies, is the period when homologous chromosomes, already being discernible
      individualized entities, begin to be close together or touching over portions of
      their lengths. This period also includes the bouquet stage: Chromosome ends,
      which have already become integral components of the inner nuclear membrane, move
      into a polarized configuration, along with other nuclear envelope components.
      Chromosome movements, active or passive, also occur. The detailed nature of
      interhomologue interactions during this period, with special emphasis on the
      involvement of chromosome ends, and the overall role for meiosis and
      recombination of chromosome movement and, especially, the bouquet stage are
      discussed.

PMID- 9928496
TI  - The immunogenetics of the seronegative spondyloarthropathies.
AB  - In none of the rheumatic diseases has the genetic contribution to pathogenesis
      been so well characterized as in the seronegative spondyloarthropathies. Most
      important has been the elucidation of the structure and effect on disease
      expression of HLA-B27, where 11 subtypes have been distinguished to date. These
      vary in frequency in different ethnic groups and seem to show differential
      disease associations. The high frequency of this gene in patients with the
      seronegative spondyloarthropathies, especially ankylosing spondylitis (AS) and
      Reiter's syndrome (RS)/reactive arthritis (ReA), has emerged as probably the best
      example of a disease association with a hereditary marker. Other HLA genes, in
      addition to HLA-B27, have been implicated in psoriasis and psoriatic arthritis.
      These include those from the HLA-C locus and from HLA-DR. In addition, recent
      family studies have implicated other genes outside the MHC that further enhance
      the susceptibility to AS.

PMID- 9928497
TI  - Aetiological agents: their molecular biology and phagocyte-host interaction.
AB  - Inflammatory joint disease can develop following an extra-articular infection.
      The term reactive arthritis was coined in order to differentiate this arthritis,
      which is often characterized by lack of culturable organisms in the joint, from
      septic arthritides. Bacteria known to trigger reactive arthritis include
      Campylobacter, Chlamydia, Salmonella, Shigella and Yersinia. Demonstration of
      bacteria or bacterial macromolecules in the joint has elicited the idea that
      reactive arthritis is a sterile process induced and maintained by antigenic
      material in the synovium. Continued synthesis of antigens to maintain synovial
      inflammation probably requires establishment of persistent bacterial infection in
      the joint, or at the primary site of infection. In the case of Chlamydia
      trachomatis, viable, metabolically-active organisms have been demonstrated to
      exist for extended periods in the joints of patients with reactive arthritis. In
      this chapter, we review the aetiological agents, and their molecular biology and
      phagocyte-host interactions, that are involved in reactive arthritis and
      spondylarthropathy.

PMID- 9928498
TI  - Animal models and in vitro models for the study of aetiopathogenesis of
      spondyloarthropathies.
AB  - Among several animal models, HLA-B27 transgenic rodents proved useful for
      investigating the interplay between genetic factors and the bacterial environment
      in the aetiopathogenesis of the spondyloarthropathies (SpA). HLA-B27 transgenic
      rats spontaneously develop a multisystemic inflammatory disease resembling human
      SpA. This disease is dependent on the presence of a normal bacterial flora and
      implicates the immune system. The presence of both T cells and antigen-presenting
      cells expressing high levels of HLA-B27 seems of critical importance in its
      pathogenesis. HLA-B27 transgenic mice also develop arthritis, under the influence
      of the bacterial flora. In both types of model, CD8+ T cells seem not to be
      necessary, arguing against the 'arthritogenic peptide' hypothesis. In vitro
      models have been used to study the immune response against bacterial agents and
      the role of HLA-B27 in human SpA. It appears that an impaired immune response
      against bacteria could be involved in the triggering of human SpA. HLA-B27 could
      be implicated at the level of interaction between host cells and bacteria in the
      driving of a specific immune response against bacterial antigens or as a target
      of an autoimmune response.

PMID- 9928499
TI  - Bacterial antigens in reactive arthritis and spondarthritis. Rational use of
      laboratory testing in diagnosis and follow-up.
AB  - An aetiological diagnosis of reactive arthritis is based on the demonstration of
      recent or ongoing infection with the causative bacterium. This may be done by
      serological demonstration of antibacterial antibodies, demonstration of the
      causative microorganism at an extra-articular site or by identification of
      bacterial nucleic acids or antigens in joint material from patients with aseptic
      arthritis. The finding of elevated titres of bacteria-specific IgG- and IgA-class
      antibodies may indicate recent or persistent infection, but has some limitations
      due to the prevalence of such antibodies among apparently healthy individuals and
      the persistence of such antibodies after the infection. While Chlamydia can be
      demonstrated in urogenital specimens in at least one-third of patients with
      Chlamydia-induced arthritis, the triggering microorganisms are usually no longer
      detectable in post-dysenteric reactive arthritides. Assays involving molecular
      amplifications have been successfully used to demonstrate bacterial nucleic acids
      in joint specimens from patients with reactive arthritis. In addition, bacterial
      antigens have been detected by immunofluorescence tests. Even though examination
      of synovial fluid and synovial membrane specimens for bacterial DNA by the
      polymerase chain reaction is increasingly used to diagnose reactive arthritis,
      such assays have not been standardized and are not generally available. While
      some problems remain, these techniques will facilitate the exact diagnosis of
      reactive arthritides in the near future.

PMID- 9928500
TI  - The spectrum of skin, mucosa and other extra-articular manifestations.
AB  - The seronegative spondyloarthropathies appear to be the genetically predisposed
      host's clinical expression to acute, subacute or chronic reaction to the invasion
      by environmental microorganisms. In the ensuing days or weeks, depending on the
      infectious load, clinical manifestations may occur ranging from constitutional
      complaints such as fever, to a variety of symptoms and/or signs related to the
      portal of entry-intestinal, genitourinary or respiratory. Within weeks or months,
      the initial or other target organs, such as the mucocutaneous, ocular and
      cardiovascular systems, may develop an acute reaction of greater or lesser
      specificity regarding the triggering agent (oral ulcers, circinate balanitis,
      erythema nodosum, acute anterior uveitis, pericarditis, heart blocks). Lastly,
      many years later, a minority of patients, probably those with a large genetic
      component, exhibit a spectrum of clinical manifestations related to those organs,
      with a chronic or recurrent course. Acute clinical manifestations--reactive
      arthritis--are prominent in the initial phase of the clinical spectrum, while
      chronic manifestations--ankylosing spondylitis--are seen at the other end of the
      spectrum.

PMID- 9928501
TI  - Enthesiopathy: clinical manifestations, imaging and treatment.
AB  - Enthesitis is a distinctive pathological feature of spondyloarthropathy and may
      involve synovial joints, cartilaginous joints, syndesmoses and extra-articular
      entheses. This review focuses on peripheral extra-articular enthesitis which is a
      clinical hallmark of spondyloarthropathy. The entheses of the lower limbs are
      more frequently involved than those of the upper limbs, and heel enthesitis is
      the most frequent. Entheseal pain may be mild or moderate as well as severe and
      disabling. Peripheral enthesitis may be observed in all forms of
      spondyloarthropathy, including the undifferentiated ones, and may for a long time
      be the only long-standing clinical manifestation of the B27-associated disease
      process. Various imaging methods have been suggested for studying peripheral
      enthesitis. Ultrasonography and magnetic resonance imaging are the most useful
      because they may show alterations of the structures involved. Therapy of
      peripheral enthesitis consists of NSAIDs, orthoses and physical therapy. Steroid
      injections, second line drugs such as sulphasalazine and radiotherapy are
      reserved for more severe cases.

PMID- 9928502
TI  - Measures of outcome in ankylosing spondylitis and other spondyloarthritides.
AB  - This chapter describes core sets that can be used in the assessment of ankylosing
      spondylitis and other spondyloarthritides. Various core sets are described for
      the evaluation of disease-controlling antirheumatic therapy, symptom-modifying
      antirheumatic drugs and physical therapy, or for use in clinical record keeping.
      These core sets describe domains and also give advice on specific instruments.
      The value of spinal mobility and acute-phase reactants in the assessment of
      ankylosing spondylitis in AS are described in more detail. The available
      radiological scoring methods are discussed.

PMID- 9928503
TI  - Spondyloarthritides in females.
AB  - Few studies have been performed regarding clinical, radiological and prognostic
      features of females with spondyloarthropathies other than ankylosing spondylitis
      (AS). In AS, clinical manifestations appear similar in men and women, whereas
      radiological features appear more frequent and severe in males. However, no
      consistent differences in outcome and mortality between men and women have been
      disclosed. Although fetal outcome is not compromised in women with
      spondyloarthropathy (SpA), the interaction of pregnancy and SpA has been studied
      in detail only in AS. Spinal disease is unchanged while peripheral arthritis and
      uveitis are suppressed during childbearing. Due to possible maternal and fetal
      side-effects, NSAIDs must be discontinued during the last 8 weeks of pregnancy,
      but during lactation several NSAIDs can be used. Treatment with sulphasalazine is
      compatible with pregnancy and lactation. Children of AS patients exhibit a
      slightly increased risk of developing SpA later in life.

PMID- 9928504
TI  - Spondylarthropathy treatment: progress in medical treatment, physical therapy and
      rehabilitation.
AB  - The monitoring and treatment of the diseases belonging to the concept of
      spondylarthropathy are related more to their clinical presentation, for example
      axial versus peripheral involvement, than to the precise diagnosis, for example,
      ankylosing spondylitis versus psoriatic arthritis. For each clinical presentation
      the treatment comprises local and systemic routes of administration but also drug
      and non-drug therapies.

PMID- 9928505
TI  - Managed occupational health.
AB  - This chapter explores the elements and techniques of managed care, managed
      health, and good management in general to identify key success factors in
      programs addressing prevention, care, disability, and rehabilitation.

PMID- 9928506
TI  - Employer-provider partnerships in advanced managed care: human assets risk
      management.
AB  - Competitive forces have increased recognition of the strategic value of
      occupational and environmental medicine. Opportunities to enhance workforce
      health and productivity abound in the managed care environment.

PMID- 9928507
TI  - The role of prevention in workers' compensation managed care arrangements.
AB  - Managed care's emphasis on restricting costs may interfere with its ability to
      assume a prevention orientation. The authors present models, derived from group
      health and workers' compensation, of successful incorporation of prevention into
      managed care arrangements.

PMID- 9928508
TI  - Occupational medicine practice guidelines.
AB  - Practice guidelines have become accepted "rules of the road" for many illnesses
      and injuries. Guidelines can be the basis for performance measures if they
      include a development step summarizing the available evidence for efficiency and
      effectiveness of maneuvers, tests, and treatments. They are particularly valuable
      for entities that have high degrees of variance in diagnostic accuracy, testing,
      and treatment. Periodic revision of guidelines can keep professional knowledge
      bases up to date. One must keep in mind that guidelines are just that-
      descriptions of normative data, observed best practices, expert consensus, or
      high-grade evidence. While they provide benchmarks for assessment and
      improvement, there may be good reasons why they do not apply to some patients.
      However, the exercise of justifying the differences can sharpen clinical judgment
      and improve outcomes.

PMID- 9928509
TI  - Disability management and occupational health.
AB  - Disability costs have an enormous impact on a corporation's profits. Medical
      managed care techniques can improve outcomes in disability management and help a
      business to remain competitive.

PMID- 9928510
TI  - State of the art case management.
AB  - Case management traditionally has been performed by occupational health nurses
      and rehabilitation professionals. The rapid growth of managed care was the
      impetus for defined standards and formal credentialing.

PMID- 9928511
TI  - Networks in workers' compensation medical delivery.
AB  - Medical networks offer discounted fees, control of the workers' compensation
      case, quality monitoring, and managed care services. As channeling of workers'
      compensation cases to networks increases, credentialed physicians will benefit.

PMID- 9928512
TI  - 24-hour programs: great idea or unrealistic?
AB  - Continuity of care, coordinated workers' compensation and group health coverages,
      and combined policies may be the solution to health care fragmentation and
      quality, financial, and productivity issues.

PMID- 9928513
TI  - Data management in occupational medicine.
AB  - The information system is a critical component of the evolving managed care
      marketplace. The authors discuss how integration and application of an optimal
      system can help to achieve the goals of an occupational medicine practice.

PMID- 9928514
TI  - Performance measures in occupational medicine: a tool to manage quality.
AB  - Managed care in occupational medicine has cut costs of workers' compensation.
      However, quality of care may have received less-than-optimal attention. The use
      of quality indicators is a new phenomenon.

PMID- 9928515
TI  - Performance measurement in workers' compensation managed care organizations.
AB  - In 1997, 29 states were applying managed care programs to workers' compensation.
      Several major initiatives to develop standard performance measures are underway.

PMID- 9928516
TI  - Managed care workers' compensation outcome measurements: how can a clinic
      compete?
AB  - Clear guidelines and standards established for physicians by managed care
      organizations are not similarly applied to clinics. Generally, measures of
      quality of care and service for clinics are ill-defined. Dr. Mueller details six
      steps to creating a meaningful, achievable set of outcome measures so that clinic
      organizations can improve and promote their care.

PMID- 9928517
TI  - Regulatory trends in workers' compensation managed care.
AB  - The authors discuss various managed care arrangements in workers' compensation
      and present a valuable chart that summarizes the managed care policies of each
      state and the district of Columbia and links the policies to their regulatory
      environments.

PMID- 9928518
TI  - Evaluating the impact of managed health care in workers' compensation.
AB  - Impairment determinations, return to work readiness, and wage replacement are
      unique components of medical services in the workers' compensation system. This
      chapter describes how to circumvent these research challenges while attempting to
      isolate the effects of managed care approaches from concurrent changes in
      workers' compensation.

PMID- 9928519
TI  - A strategic approach to occupational injuries.
AB  - The development of an integrated risk management approach to occupational
      injuries at Conrail had an enormously positive impact on injury incidence, lost
      work days, and company costs. Dr. Comstock describes managed care techniques that
      facilitate interface between quality assurance and risk management.

PMID- 9928520
TI  - Prevention of work-related disability.
AB  - The authors, reporting from Kaiser Permanente, describe a new program that may be
      helpful to other managed care providers in preventing workplace injury and
      minimizing disability after injury.

PMID- 9928521
TI  - Physician role change in managed care: a frontline report.
AB  - Dr. Christian, Vice President and Chief Medical Officer of ManagedComp, Inc.,
      describes the company's new managed compensation program in which the physician's
      role is expanded to include more accountability.

PMID- 9928522
TI  - The market for occupational medicine managed care.
AB  - The metamorphosis of the health care market has opened a window of opportunity
      for occupational medicine programs and practices to assume a critical role in the
      delivery of managed occupational and personal health care services. This chapter
      offers practical suggestions and tips.

PMID- 9928523
TI  - Inhibitors of cell growth. Introduction.

PMID- 9928524
TI  - The growth-inhibitory effects of TGF beta.

PMID- 9928525
TI  - Big brothers are watching: the retinoblastoma family and growth control.

PMID- 9928526
TI  - The growth-regulatory role of p21 (WAF1/CIP1).

PMID- 9928527
TI  - Mechanisms of cell cycle blocks at the G2/M transition and their role in
      differentiation and development.

PMID- 9928528
TI  - Mechanisms of interferon action.

PMID- 9928529
TI  - Growth-inhibiting N-substituted endogenous peptides.

PMID- 9928530
TI  - Endogenous angiogenesis inhibitors: angiostatin, endostatin, and other
      proteolytic fragments.

PMID- 9928531
TI  - Inhibitors of preadipocyte replication: opportunities for the treatment of
      obesity.

PMID- 9928533
TI  - Growth inhibition of human fibroblasts in vitro.

PMID- 9928532
TI  - Growth inhibitors for mammary epithelial cells.

PMID- 9928534
TI  - The question of metazoan monophyly and the fossil record.

PMID- 9928535
TI  - The evolution of the lower Metazoa: evidence from the phenotype.

PMID- 9928536
TI  - Origin and phylogeny of metazoans as reconstructed with rDNA sequences.

PMID- 9928537
TI  - Sponges (Porifera) molecular model systems to study cellular differentiation in
      Metazoa.

PMID- 9928538
TI  - The notion of the Cambrian pananimalia genome and a genomic difference that
      separated vertebrates from invertebrates.

PMID- 9928539
TI  - Evolution of metazoan collagens.

PMID- 9928540
TI  - Evolution of early Metazoa: phylogenetic status of the Hexactinellida within the
      phylum of Porifera (sponges).

PMID- 9928541
TI  - Structure and evolution of genes encoding polyubiquitin in marine sponges.

PMID- 9928542
TI  - Diet and mammary gland carcinogenesis.
AB  - The variation in human breast cancer incidence rates worldwide suggests that
      lifestyle factors, especially diet, influence breast cancer risk. There is
      convincing evidence that diets associated with rapid growth and greater adult
      height increase breast cancer risk. In addition, diet and other lifestyle factors
      which lead to high body mass, especially during postmenopausal years, also appear
      to increase risk. Several dietary components have been evaluated in
      epidemiological and animal studies for their role in breast cancer. Dietary fat
      was once implicated in the high incidence of breast cancer in the Western world,
      but its role in breast cancer is now controversial. In contrast, alcohol
      consumption is currently recognized as the best-established dietary risk factor
      in this disease. Carcinogens that cause mammary gland cancer in rats such as
      heterocyclic amines and polycyclic aromatic hydrocarbons are found in cooked
      meat, but it is not yet known if these carcinogens are etiological factors in
      human breast cancer. Fruits and vegetables are rich in potential chemopreventive
      factors that may lower breast cancer risk. Practical approaches to dietary
      modification that include increasing fruit and vegetable consumption, eating a
      low fat diet, reducing cooked meat consumption, and avoiding alcohol are likely
      to be of potential overall benefit in lowering the risk of human breast cancer.

PMID- 9928543
TI  - Prevention of breast cancer: focus on chemoprevention.
AB  - Present prospects of breast cancer prevention are being developed in three main
      areas: (a) genetics, to understand the real importance of familial breast cancer
      and genetic testing; (b) lifestyle, to study various risk factors, including
      delayed first pregnancies and smaller number of pregnancies, and months of breast
      feeding; (c) chemoprevention, to identify chemical agents potentially able to
      inhibit the development of invasive cancer either by blocking the DNA damage that
      initiates carcinogenesis or by arresting or reversing the progression of
      premalignant cells. Different target populations for breast cancer
      chemoprevention may be recognized. Primary chemoprevention may involve a wide
      population of healthy women with a moderate risk due to nonpenetrant genetic
      factors (e.g., one first-degree relative with breast cancer) or exposure to known
      promoting agents (e.g., hormone replacement therapy). A second level of primary
      chemoprevention may involve a limited population at very high risk because of
      highly penetrating genetic predisposition to cancer (e.g., BRCA1 mutation
      carriers). Secondary chemoprevention may involve subjects with premalignant or
      early malignant lesions, e.g., breast atypical hyperplasia and carcinoma in situ
      or microinvasive disease. Prevention trials using clinical endpoints are always
      subject to high costs. Also, the risk of unexpected detrimental effects has
      recently been high-lighted, and much emphasis has been put on the search for
      intermediate, surrogate endpoints. Surrogate endpoints are biological markers
      that may be assessed or observed prior to the clinical appearance of the disease,
      bearing some relationship to the development of that disease. They are referred
      to as intermediate since they occur some time between a given intervention that
      affected the disease process and the time of the clinical diagnosis of the
      disease. The use of surrogate endpoint biomarkers in pivotal cancer
      chemoprevention trials may lead to a rational choice of agents which are likely
      to affect cancer incidence in subsequent phase III trials.

PMID- 9928544
TI  - Estrogen/hormone replacement therapy and the etiology of breast cancer.
AB  - ERT/HRT is clearly of use in relieving menopausal symptoms such as hot flashes
      and genitourinary changes. ERT/HRT also clearly reduces the risks of osteoporotic
      fracture, of cardiovascular events and deaths, and of developing colon cancer.
      ERT and, perhaps even more, HRT are, however, associated with an increased risk
      of developing breast cancer. This effect becomes more marked with long-term use
      (> or = 10 years); ERT/HRT use for more than 10 years is also associated with an
      increase in deaths from breast cancer. Because the underlying mortality risk for
      the average woman is, however, much greater from cardiovascular disease
      (approximately 22%) than from breast cancer (approximately 3.3%), the reduction
      in risk of cardiovascular death associated with ERT/HRT (from 22% to 15%) much
      outweighs the increase in risk of death from breast cancer (from 3.3% to 4.1%).
      Thus, overall, the average woman will gain more year(s) of life than she will
      lose by taking ERT/HRT. Even for a woman with a high risk of breast cancer and a
      low risk of cardiovascular disease, there will still be a net, although lower,
      gain in year(s) of life. Thus, the use of ERT/HRT would seem well worth
      considering for a well woman at the time of menopause.

PMID- 9928545
TI  - Experimental pathology and breast cancer genetics: new technologies.
AB  - The goal is to understand the critical events in tumour development and to apply
      this understanding to new approaches to diagnosis, prevention and treatment. It
      is clear that breast cancer is a heterogeneous disease at the molecular level,
      raising the possibility of a future functional classification based on mechanisms
      rather than morphology. These molecular phenotypes will also confer predictive
      value on the potential of the tumour to invade, metastasise and respond to or
      resist new therapeutic strategies. Studies of the genome in individuals are
      predicted also to enable the identification of polymorphisms that are associated
      with increased susceptibility to environmental factors, in addition to possibly
      explaining de novo variations in responses to drugs and radiation. The difficulty
      is how to identify which, of the approximately 30,000 genes expressed by a
      typical cancer cell alone or in combination, are the ones involved in these
      processes. The majority of breast cancers have such a multitude of molecular
      changes that it is difficult to distinguish between those that are critical to
      tumour progression and those that are epiphenomena of genetic instability and
      abnormalities in DNA repair. The identification of the earliest events in
      carcinogenesis must be the best hope, as it will then be possible to target the
      events that predispose to other secondary changes before they occur. Genomics and
      proteomics is the current hope to take us forward. This involves the application
      of a number of new technologies to facilitate the profiling of individual
      tumours, including laser-guided microdissection of microscopic lesions,
      comparative genomic hybridisation and loss of heterozygosity analysis of DNA
      using microarray technology to study DNA and expressed RNAs and protein profiling
      using 2D gel mass spectroscopy. With over 100,000 mRNAs and proteins to examine
      in complex tissues and in various combinations, there is obviously going to be a
      requirement for a large investment in computing power (bioinformatics) to
      facilitate the analysis of these data in relation to the clinical characteristics
      of the individual tumour and the patient.

PMID- 9928546
TI  - Update on breast cancer susceptibility genes.
AB  - BRCA1 and BRCA2 have now been isolated and a large number of families
      characterized for the presence of mutations in these breast cancer susceptibility
      genes. Data from these studies are beginning to provide us with answers to many
      important questions. It is clear that estimates of attributable risk and
      penetrance are dependent on the population being studied. For example, studies of
      large, extensively affected families suggest that 45% of inherited breast cancer
      is due to BRCA1 mutations, while similar studies in individuals ascertained from
      breast cancer risk evaluation clinics suggest that the attributable risk is only
      15%-20%. Similarly the large families yield penetrance estimates of 87% by age
      85, while a more population-based study suggests somewhat lower rates--60% by age
      70. In addition, studies of BRCA1-related tumors suggest that there may be some
      important molecular differences as compared to sporadic tumors, with a
      predominance of high grade lesions that are ER negative and an increased rate of
      p53 mutations. Controversy remains about the potential for genotype/phenotype
      correlation, and previous anecdotal reports of improved survival in families with
      familial breast cancer have yet to be fully evaluated. Finally, clinical
      recommendations are being formulated, with current recommendations centered on
      screening for breast cancer risk and prophylactic oophorectomy for presumed
      reduction of ovarian cancer risk.

PMID- 9928547
TI  - IGF-I physiology and breast cancer.
AB  - Recent studies imply that IGF-I levels vary greatly between normal women, and
      that premenopausal breast cancer risk is increased among women with higher IGF-I
      levels. It is known that tamoxifen lowers IGF-I levels, but further research is
      needed to determine whether antiestrogens will be of particular value in risk
      reduction for women with high IGF-I levels, and also to determine if IGF-I levels
      can indeed be used as an intermediate endpoint in risk reduction interventions.
      With respect to adjuvant therapy, we currently have convincing data that
      antiestrogens have moderate IGF-I lowering actions, but it remains unclear to
      what extent these contribute to the therapeutic effect of these compounds.
      Ongoing trials are addressing this question, as well as the hypothesis that
      interventions that increase IGF-I suppression will be associated with reduced
      relapse rates.

PMID- 9928548
TI  - Determination of clinical utility of tumor markers: a tumor marker utility
      grading system.
AB  - TMUGS should help make order out of the chaos that exists in evaluation of tumor
      markers for clinical use. Although it seems cumbersome at first, application of
      this system by expert reviewers should help separate those markers for which
      clinical utility clearly exists from those markers for which either more data are
      necessary or for which further consideration can be discarded. Perhaps as
      important, this system may serve as a framework in which clinical and
      translational investigators can design studies prospectively to generate LOE I or
      II data, and thus hasten the acceptance of new biologic factors into routine
      clinical practice.

PMID- 9928549
TI  - How can prognostic and predictive factors in breast cancer be used in a practical
      way today?
AB  - Since the 1995 St. Gallen conference the standard prognostic and predictive
      variables have not changed. Good treatment planning (and clinical trial entry and
      stratification) can be made on the basis of TNM staging, age, and ER and
      menopausal status. Three years from now, in 2001, this situation will have
      changed enormously. This will be achieved by better designs for prognostic
      studies, studies of predictive factors with definitive data from large,
      statistically powerful cooperative group trials, and perhaps simple computer
      based tools to make projections and present data clearly. These advances will
      lead to still better-individualized selection of adjuvant therapy for breast
      cancer patients.

PMID- 9928550
TI  - Strategies for the development of vaccines to treat breast cancer.
AB  - The characterization of tumor-associated antigens recognized by cellular or
      humoral effectors of the immune system has opened new perspectives for cancer
      therapy. Several categories of cancer-associated antigens have been described as
      targets for cytotoxic T lymphocytes (CTLs) in vitro and in vivo: "cancer-testis"
      (CT) antigens expressed in different tumors and normal testis, melanocyte
      differentiation antigens, point mutations of normal genes, antigens that are
      overexpressed in malignant tissues, and viral antigens. Clinical studies using
      peptides derived from these antigens have been initiated to induce specific CTL
      responses in vivo. Immunological and clinical parameters for the assessment of
      peptide-specific reactions have been defined, i.e., induction of delayed-type
      hypersensitivity (DTH), CTL, autoimmune, and tumor regression responses.
      Preliminary results demonstrate that tumor-associated peptides alone elicit
      specific DTH and CTL responses leading to tumor regression after intradermal
      injection. GM-CSF was proved to be effective in enhancing peptide-specific immune
      reactions by amplification of dermal peptide-presenting dendritic cells. Long
      lasting complete tumor regressions have been observed after induction of CTLs by
      peptide immunization. However, in a few cases where there was disease progression
      after initial tumor response, loss of either the tumor antigen targeted by CTLs
      or of the presenting MHC class I molecule was detected as the mechanism of immune
      escape under immunization in vivo. Based on these observations, cytokines to
      enhance antigen and MHC class I expression in vivo are being evaluated to prevent
      immunoselection. Recently, a strategy utilizing spontaneous antibody responses to
      tumor-associated antigens (SEREX) has led to the identification of a new CT
      antigen, NY-ESO-1. In a melanoma patient with high titer antibody against NY-ESO
      1, strong HLA-A2-restricted CTL reactivity against the same antigen was also
      found. Clinical studies involving tumor antigens that induce both antibody and
      CTL responses will show whether these are better candidates for immunotherapy of
      cancer.

PMID- 9928551
TI  - Hypothesis and practice: are there several types of treatment for ductal
      carcinoma in situ of the breast?
AB  - Currently, we approach DCIS based on its morphology rather than its etiology.
      However, morphologically normal-appearing tissue surrounding areas of DCIS may
      reveal losses of heterozygosity similar to the primary tumor (Lakhani et al.
      1995; Stratton et al. 1995; Radford et al. 1995; Fujii et al. 1996). In all
      likelihood, genetic changes precede morphologic evidence of malignant
      transformation. We in medicine must learn how to recognize these genetic changes,
      exploit them, and, in the future, prevent them. DCIS is a lesion in which the
      complete malignant phenotype of unlimited growth, angiogenesis, genomic
      elasticity, invasion, and metastasis has not been fully expressed. With
      sufficient time, most noninvasive lesions will learn how to invade and
      metastasize. We must learn how to prevent this.

PMID- 9928552
TI  - Ductal carcinoma in situ of the breast: histological classification and genetic
      alterations.
AB  - Ductal carcinoma in situ (DCIS) of the breast represents a proliferation of
      malignant epithelial cells within the ducts and lobules of the breast, without
      invasion through the basement membrane. It is believed that all invasive
      carcinomas are preceded by DCIS; however, it is not known what proportion of
      patients with DCIS will develop invasive carcinoma and after what interval. DCIS
      is heterogeneous with respect to its clinical presentation, mammographic
      abnormalities, histology and biology. The risk of progression to invasive
      carcinoma depends on the histologic type of DCIS and the size of the lesion; in
      the future, the analysis of the genetic alterations may also help in predicting
      the risk of progression to invasive breast cancer. As the risk of progression to
      invasive breast cancer (and the development of metastases) greatly influences the
      choice of treatment for DCIS, it is of importance to be able to make a reliable
      estimate of this risk of progression. In this chapter, the histologic
      classification of DCIS and the genetic alterations that have been found to date
      are discussed.

PMID- 9928553
TI  - Trials of treatment for non-invasive breast cancer.
AB  - Non-invasive breast cancer can be of either the ductal or the lobular type. While
      the former is often associated with progression to invasive cancer at the same
      site, lobular carcinoma in situ (LCIS) is a risk factor for invasive cancer
      rather than a precursor. As a result, LCIS has been used as one entry criterion
      for the International Breast Intervention Study in which women at increased risk
      because of histological findings or family history are randomised to receive
      either tamoxifen 20 mg daily or placebo for 5 years. Four randomised trials have
      examined treatment options for ductal carcinoma in situ (DCIS) and all have
      demanded complete local excision as a necessary qualification for entry. Because
      of this, up to half the cases of DCIS were ineligible for entry since the disease
      was too extensive and was therefore usually treated by total mastectomy. In most
      studies--NSABP B-17, EORTC 10853 and Swedish trial--the randomisation was between
      breast irradiation and observation. Only one trial, NSABP B-17, has published
      results, and these suggest that progression to invasive cancer is reduced by
      irradiation. Withholding radiotherapy did not affect mortality. The UK DCIS trial
      is comparing the effects of both radiotherapy and tamoxifen, but as yet no
      results are available. At present, radiotherapy should not be used as standard
      treatment of completely excised DCIS. Appropriate indications for irradiation
      will be determined when results of histologically characterised cases
      participating in mature trials become available. Total mastectomy remains the
      standard treatment for extensive DCIS, but the next generation of trials may
      examine the role of endocrine manipulation in cases with estrogen-receptor
      positive tumours.

PMID- 9928554
TI  - The axilla: to clear or not to clear? That is the question!
AB  - The prime objectives for axillary dissection are staging and treatment to cure.
      No physical examination, no imaging techniques, and no tumor markers can replace
      axillary dissection for staging. Further, axillary node status in potentially
      curable breast carcinomas is still considered the single best predictor of
      outcome and the primary determinant of the use of systemic therapy. Finally,
      locoregional tumor control seems to improve survival, emphasizing meticulous
      axillary dissection. Today, the question to be asked is not whether or not to
      clear the axilla; rather, the question should go: How do we distinguish node
      negative patients from those who are node-positive without clearing the axilla
      unnecessarily? No surgeon would advocate dissecting the axilla in node-negative
      patients if nodal status could be ascertained by a different technique. Ongoing
      trials addressing the reliability of the sentinel node technique seem promising,
      and this technique may perhaps in the near future solve the problem of
      distinguishing node-negative patients from those with axillary spread. For the
      time being, the necessity of determining axillary status and to treat for cure
      can hardly be questioned. Therefore, once axillary spread has been demonstrated
      in one way or another, an adequate and meticulous axillary dissection should be
      performed.

PMID- 9928555
TI  - Axillary clearance in operable breast cancer: still a necessity?
AB  - Complete axillary dissection, as part of radical mastectomy, was the standard of
      care for the first three-quarters of this century. Long-term follow-up of these
      patients showed substantial cure rates for positive-node patients before systemic
      therapy was available, indicating a therapeutic value to nodal dissection. There
      was also good control of the axilla; axillary recurrence after removal of
      positive nodes was quite low. Even today, in patients with positive nodes,
      complete axillary clearance as part of a modified radical mastectomy or a breast
      conservation approach with lumpectomy leads to control of the axilla and complete
      axillary staging, allowing medical oncologists to tailor their systemic treatment
      to the total number of nodes involved. Today, due to a combination of factors
      including patient awareness and the ability of mammography to detect smaller
      lesions, many women present with small cancers that carry a much lower risk of
      axillary involvement. Whereas a complete dissection is indicated for patients
      with clinically involved nodes, a level I-II dissection is the standard in most
      centers for patients with clinically negative nodes. In those patients with very
      small (T1a, T1b) cancers, the role of sentinel lymphadenectomy is being explored;
      it may spare these patients the morbidity of complete axillary dissection.

PMID- 9928556
TI  - Sentinel lymphadenectomy: a safe answer to less axillary surgery?
AB  - Lymphatic mapping techniques have the potential of changing the standard of
      surgical care of breast cancer patients. This paper reports a prospective study
      documenting the safety and efficacy of sentinel lymph node biopsy in 167 breast
      cancer patients and reviews the world literature on the procedure. METHODS: One
      hundred sixty-seven patients with newly diagnosed breast cancers underwent a
      prospective trial of intra-operative lymphatic mapping using a combination of
      vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph
      node (SLN) was defined as a blue node and/or "hot" node with a 10/1 ex-vivo gamma
      probe ratio of SLN to non-SLN. All SLN were bi-valved, step-sectioned, and
      examined with routine H&E stains and immunohistochemical stains for cytokeratin.
      Cytokeratin-positive SLN were defined as any SLN with a defined cluster of
      positive staining cells which could be confirmed histologically on H&E sections.
      Finally, a review of the worldwide data was undertaken using a uniform analytical
      method to compare the rates of sensitivity, diagnostic accuracy, and false
      negatives of SLN mapping. RESULTS: In 167 patients, 337 SLN were harvested, for
      an average of 2.01 SLN/patient. Fifty-two (31.1%) of the patients had metastasis
      in the SLN. In the 115 patients with negative SLN, 1 was found to have tumor in
      higher axillary nodes, for a false negative rate of 0.88%. Fifty-nine (37.8%) of
      the patients were diagnosed by fine-needle aspiration, 89 (53.3%) by excisional
      biopsy, and 19 (11.4%) by core biopsy. Positive SLN were identified in 1/17
      (5.9%) patients with DCIS. Metastasis was found in 33/115 (28.7%) of the patients
      with infiltrating ductal tumors and in 11/19 (57.9%) of the patients with
      infiltrating lobular tumors. Positive SLN were identified in 7/16 (43.7%) of the
      patients with mixed cellularity tumors. Metastasis in the SLN was detected in
      7/55 (12.7%) of the 59 patients with T1a-T1b tumors and in 21/58 (36.2%) of the
      patients with T1c tumors. Positive SLN were found in 17/30 (56.7%) of the
      patients with T2 tumors and in 6/7 (85.7%) of the patients with T3 tumors. A
      literature review of 731 patients (including this study) demonstrates a
      sensitivity rate of 95% and a diagnostic accuracy rate of 98%. The overall false
      negative rate is 3.1%. CONCLUSIONS: This study demonstrates that SLN biopsy is a
      highly sensitive and accurate method of predicting axillary nodal status. It is a
      reproducible technique that is easily learned. The future addition of more
      sensitive methods such as PCR evaluation of nodal involvement may reduce the need
      for widespread use of adjuvant chemotherapy with its high cost and attendant
      morbidity and mortality. We believe that this technique will eventually become
      the standard of care in the treatment of breast cancer, particularly for T1 and
      T2 lesions and perhaps also for high-grade DCIS tumors.

PMID- 9928557
TI  - Endoscopic surgery to the axilla--a substitute for conventional axillary
      clearance?
AB  - Nonpalpable, mammographically detected breast cancers are on the increase. The
      percentage of patients with histologically involved nodes is therefore
      decreasing. Axillary clearance aims at reducing the probability of later clinical
      involvement of the axilla and at establishing a sound basis for adjuvant
      treatment planning. Minimally invasive techniques have been applied to a growing
      number of surgical procedures now including exploration of the axilla. The
      technique used and results achieved in a series of 50 consecutive patients
      treated by liposuction and axilloscopy by one single surgeon, including all the
      patients from the very first attempt, are presented here. Patients were excluded
      with palpable lymph nodes or a primary tumor in the direct vicinity of the axilla
      that could be injured by the liposuction canula. The average number of lymph
      nodes removed was 13.4. Thirty-four percent of patients had involved nodes. The
      mean number of involved nodes in these patients was 3.1. After a median follow-up
      time of only 15 months no axillary recurrences or trocar site metastases have
      been found in the first 40 patients. Using a self-assessment questionnaire, the
      patients rate this technique as excellent. There was no lymphedema. The cosmetic
      result is certainly better than after conventional axillary clearance. Great
      experience of laparoscopic surgery and an excellent knowledge of the axillary
      anatomy are prerequisites for the practice of axilloscopic treatment of the
      axilla. The working space within the axilla is small and a number of structures
      need absolutely to be preserved. A longer follow-up period than the one so far
      achieved in this series or any other in the literature to date is necessary
      before this technique can be generally recommended.

PMID- 9928558
TI  - Surgical considerations in preoperative chemotherapy of breast cancer.
AB  - Primary systemic chemotherapy for breast cancer was initially directed at
      downsizing tumors to make them acceptable candidates for breast-conserving
      surgery. Later trials used this approach in the hope of improving disease-free
      survival and overall survival. Results from NSABP protocol B-18 indicate
      significant initial tumor response and downstaging of lymph nodes in 30% of
      patients. Patients with small tumors were more likely to experience complete
      clinical response and complete pathologic response. Patients with larger tumors
      whose surgeons would have chosen mastectomy often responded with tumor decrease
      to a size at which lumpectomy was considered feasible. The local recurrence rate
      in these patients was higher than in those patients selected for lumpectomy
      primarily. Nevertheless, even with a higher rate of ipsilateral breast tumor
      recurrence, approximately 90% of women older than 50 years and 83% of younger
      women had successful breast-conserving surgery. There was no difference in
      disease-free survival or overall survival between preoperative and postoperative
      chemotherapy groups. The response of patients to initial chemotherapy can be a
      useful tool in exploring the biology of breast cancer.

PMID- 9928559
TI  - Integration of plastic surgery in the course of breast-conserving surgery for
      cancer to improve cosmetic results and radicality of tumor excision.
AB  - Integration of plastic surgery is currently widely practiced in cases of
      mastectomy. Immediate breast reconstruction with an implant or autologous tissue
      procedures is frequently proposed to the patient before the mastectomy. However,
      breast conserving surgery (BCS) is recognized as the treatment of choice in most
      cancers: breast conservation is proposed in more than 70% of the patients with
      primary cancer treated at the European Institute of Oncology in Milan. This high
      percentage of preservation has been made possible by the integration of plastic
      surgery at the time of primary surgery. The size of the tumorectomy remains a
      matter of discussion. Based on the Milan II trial and Holland's pathological
      studies, Veronesi recommended so-called "local radical surgery." For a tumor 1 cm
      in size, a free margin of 2 cm produces a final specimen at least 5-6 cm in
      diameter. In small or medium-sized breasts, such a resection results in a wide
      glandular defect and poor esthetic results if direct closure is carried out.
      Plastic surgery derived from reduction mammaplasty procedures allows much better
      final cosmetic results, which is the goal of conservative treatment. In 25% of
      our patients treated with BCS, the plastic surgeon is called upon by the general
      surgeon to close the glandular defect. However, such glandular remodeling changes
      the size and position of the breast. Therefore, in 15% of these cases a symmetry
      procedure is performed on the opposite breast. The reduction procedure in the
      opposite breast should be taken as a good opportunity to check the glandular
      tissue. Special attention should therefore be given to the contralateral
      mammogram in order to focus the glandular resection on the most dubious areas.
      Occult carcinomas, half of them infiltrating, were found in 4% of a series of 350
      symmetry procedures performed during breast reconstruction at the Gustave Roussy
      Cancer Institute. In conclusion, close collaboration between oncologists and
      plastic surgeons is required not only to obtain the best cosmetic results but
      also to allow improved radicality of the tumor resection and a histological check
      up of the contralateral breast.

PMID- 9928560
TI  - Is primary chemotherapy useful for all patients with primary invasive breast
      cancer?
AB  - Chemotherapy dose intensification in breast tumours is being evaluated in many
      multicentre trials, its indication being based on a clinical response in high
      risk patients, thus selecting for tumours with rapid proliferation and low
      resistance. However, results from randomized trials are still pending. Clinical
      and pathological responses to therapy are valuable surrogate endpoints following
      primary chemotherapy. They will make it possible to distinguish at an early stage
      between patients who still retain an apoptotic response to chemotherapy and those
      patients whose disease will progress rapidly due to resistance mechanisms. For
      practical purposes, patients at risk and capable of responding represent the
      population of choice for primary systemic chemotherapy. Thus, by investigating
      mechanisms of response and resistance during the first courses of treatment we
      may target chemotherapy at those patients likely to benefit most from this
      treatment. A number of immunotherapy and vaccination trials are being conducted
      in many different centres. There is a lot of anecdotal evidence that cancer
      vaccines could help patients, but little yet in the way of solid, reproducible
      clinical data. Best responses to clinical testing would ideally be expected in
      early-stage disease because there is less tumour bulk and the patient's immune
      system is still able to respond. Patients with early breast cancer who are at
      high risk of recurrence and who have failed to respond to primary chemotherapy
      might be given the option of participating in adjuvant vaccination trials
      following the completion of local therapy.

PMID- 9928562
TI  - Why and how to combine chemotherapy and radiation therapy in breast cancer
      patients.
AB  - The ideal sequencing of CT and radiation therapy in early-stage breast cancer
      treated with breast-conserving surgery and RT is not known. There is evidence
      that delaying CT might have an adverse impact on systemic control, while delaying
      RT might adversely affect local control. Concurrent CT and full-dose RT might
      minimize the above tradeoffs, but is associated with increased toxicity.
      Concurrent CT and reduced-dose RT is a novel approach to address these issues,
      but requires additional formal evaluation before clinical use. In the absence of
      definitive information, clinicians should balance each patient's risk for
      systemic recurrence and local-regional recurrence. For example, a patient with a
      large number of positive nodes but clearly negative margins would be an
      appropriate candidate for adjuvant therapy starting with CT and continuing with
      RT at the completion of CT. Alternatively, a patient with node-negative disease
      with close or focally positive margins might be an appropriate candidate for
      initiating RT sooner. Current treatment regimens which deliver CT in a "short"
      time period [i.e., Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide)
      delivered in four 3-week cycles] may represent a reasonable tradeoff with regard
      to promptly starting systemic therapy while initiating RT within 3 months of
      surgery. It is possible that optimizing the way RT and CT are combined is
      important in achieving the highest survival rate and in reducing long-term
      adverse effects. There is unfortunately very little solid information from
      randomized clinical trials addressing this question, and considerable controversy
      remains regarding the optimal approach to integrating these modalities.
      Additional randomized clinical trials addressing this important clinical question
      are needed.

PMID- 9928561
TI  - The primary use of endocrine therapies.
AB  - Primary endocrine therapy is potentially superior to primary chemotherapy in
      patients with ER-positive tumors. The ability to give endocrine therapy
      perioperatively may be a better test than chemotherapy of the hypothesis that the
      events accompanying surgery affect prognosis. However, a major problem in all
      studies of primary endocrine therapy is that there has been no clear experimental
      test of preoperative versus postoperative therapy. This is because the major
      thrust of treatment has been in the elderly with the purpose of determining
      whether surgery can be avoided altogether. The fact that in ER-positive tumors
      primary endocrine therapy is associated with similar response rates to
      chemotherapy make it an attractive therapy for older women. This is the group
      where adjuvant chemotherapy has not been adequately tested (> or = 70 years of
      age). In contradistinction, adjuvant endocrine therapy shows marked survival
      benefits in patients with ER-positive tumors in these age groups (Table 1). It
      appears likely that primary endocrine therapy will allow breast conservation and
      prognostic information as is seen with chemotherapy. A major question which
      requires answering is whether primary endocrine therapy will improve survival
      more than adjuvant therapy alone. Although ER status is a good marker of
      responsiveness, its specificity, in particular, is not optimal. The ability to
      assess the dynamic effects of primary endocrine therapy by sequential biopsy and
      measurement of biological responses to oestrogen deprivation may allow us to
      predict precisely the patients likely to benefit from treatment. This clinical
      scenario allows us to use other potentially useful assessments such as the non
      invasive estimation of angiogenesis using quantitative imaging techniques of
      blood flow. The newer anti-estrogens and aromatase inhibitors appear ideally
      suited to primary therapy since they have rapid and profound inhibitory
      activities, few or no agonist effects, and low side effect profiles. A
      preoperative trial of Faslodex is planned by the EORTC and another with Arimidex
      is under consideration by the ATAC (Arimidex, tamoxifen and combined) Trialist
      Group (Fig. 7). The precise design of these studies will require considerable
      thought.

PMID- 9928563
TI  - Novel approaches using radiation therapies.
AB  - The updates of the Danish DBCG 82b trial and the British Columbia trial have
      confirmed a significant overall survival benefit with postoperative radiation
      therapy in patients with high-risk disease. These trials together with in-depth
      analyses of previous studies suggest that the mechanism of the survival benefit
      is eradication of subclinical locoregional deposits of tumor cells with a
      potential for further dissemination if left untreated. Despite these findings,
      several questions remain largely unanswered concerning the optimal way to
      integrate radiation therapy into routine clinical practice. For instance, which
      subgroups are likely to benefit from comprehensive treatment including the
      peripheral lymphatics as opposed to treatment of the breast/chest wall alone? The
      available randomized trials and overviews have convincingly demonstrated that it
      is essential to minimize long-term radiation side effects in the myocardium in
      order to achieve an overall survival benefit. An appropriate treatment technique
      is therefore essential. Individual treatment planning should be encouraged since
      some patients have an "unfavorable anatomy" with the heart located anteriorly in
      the mediastinum. Such patients may receive a high cardiac dose-volume even with
      conventional tangential field irradiation that does not include the internal
      mammary nodes.

PMID- 9928564
TI  - Molecular biology of the estrogen receptor aids in the understanding of tamoxifen
      resistance and breast cancer prevention with raloxifene.

PMID- 9928565
TI  - Aromatase inhibitors and their use in the adjuvant setting.
AB  - Over the past decade several novel aromatase inhibitors have been introduced into
      clinical practice. The discovery of these drugs followed on from the observation
      that the main mechanism of action of aminoglutethemide was via inhibition of the
      enzyme aromatase, thereby reducing peripheral levels of estradiol in post
      menopausal patients. The second-generation drug 4-hydroxyandrostenedione was
      introduced in 1990, and although its use was limited by its need to be given
      parenterally, it was found to be a well-tolerated form of endocrine therapy. The
      third-generation inhibitors include vorozole, letrozole, anastrozole and
      exemestane, the former three being non-steroidal inhibitors, the latter being a
      steroidal inhibitor. All these compounds are capable of reducing estrogen levels
      to within 5%-10% of baseline levels compared with 20%-30% base line levels in the
      case of 4-hydroxyandrostenedione. Studies are currently in progress to determine
      the value of these third-generation aromatase inhibitors in the adjuvant setting.
      These studies include head-to-head comparison of aromatase inhibitor with
      tamoxifen, sequential aromatase inhibitor after tamoxifen and first-line
      aromatase inhibitor followed by adjuvant tamoxifen. Current issues revolve around
      the toxicity of these compounds in terms of effects on the cardiovascular system
      and bone.

PMID- 9928566
TI  - GnRH analogues and ovarian ablation: their integration in the adjuvant strategy.
AB  - Ovarian ablation, either by surgery or radiation, has been clearly shown to be an
      effective adjuvant therapy for pre-menopausal women following breast cancer
      surgery. The 1995 Oxford Overview confirmed this effect in trials of ovarian
      ablation compared to no other systemic adjuvant therapy. In trials of
      chemotherapy plus ovarian ablation compared to the same chemotherapy alone,
      however, the addition of ovarian ablation, although tending to add benefit, did
      not achieve a statistically significant positive effect. Data exist from a
      variety of randomized trials of adjuvant chemotherapy suggesting that pre
      menopausal women who become amenorrhoeic after chemotherapy achieve a better
      outcome than those who continue to menstruate. These data are not consistent
      among all trials, however. There are few trials that compare ovarian ablation
      directly to chemotherapy, but those few that exist, as well as indirect
      comparisons, suggest that the effects of ovarian ablation, particularly in
      estrogen-receptor-positive women, are similar in magnitude to those of
      chemotherapy. Several large trials comparing chemotherapy to the LH-RH analogue
      Zoladex (goserelin) and studying the addition of Zoladex to adjuvant chemotherapy
      will be available by 1999 or 2000 and will provide considerable additional
      information on this matter.

PMID- 9928567
TI  - Putting the taxanes to work: unanswered questions.
AB  - The promising activity of taxanes in advanced breast cancer patients has prompted
      the investigators to explore their role in the adjuvant setting. Methodological
      issues, still unsolved pharmacokinetic and pharmacodynamic problems, and
      potential severe toxicities could jeopardize these attractive regimens and should
      be taken into account in the design and interpretation of adjuvant trials. In
      order to minimize the methodological drawbacks, the potential role of taxanes in
      the adjuvant setting should be assessed in clinical trials powered to detect an
      absolute survival increase of near 7% at 10 years. The use of paclitaxel in
      combination with anthracyclines is complicated by pharmacokinetic interactions
      which may be responsible for unexpected side effects and/or subadditive
      cytotoxicity. Moreover, possible interactions between taxanes and tamoxifen are
      still unclear, and therefore more data are necessary before recommending the
      combined use of the two drugs in the adjuvant setting. Nowadays, the majority of
      breast cancer patients receive conservative surgery followed by radiotherapy;
      when adjuvant taxanes are used, radiotherapy should be delayed because of their
      radiosensitization effect, with potential detrimental effects. Finally, the
      majority of side effects of taxane-containing regimens are short-lasting and
      reversible, but other potential toxicities, such as the cardiotoxicity and long
      term possible sequelae of the use of high-dose steroids, need long-term
      evaluation.

PMID- 9928568
TI  - Putting taxanes to work in operable breast cancer: a search for selective
      indications from empirical studies.
AB  - The taxanes paclitaxel and docetaxel are the prototype drugs of a new class of
      anticancer drugs that exploits a completely new mechanism of action. Their
      testing in metastatic breast cancer has been extensive. The results indicating
      very high response rate with either taxane have given rise to an unprecedented
      effort in the scientific community to define their optimal application in all
      stages of the disease. In metastatic breast cancer, initial data suggest that
      paclitaxel may increase the survival obtained with standard combinations such as
      CMFP, and similarly promising studies of docetaxel are almost complete.
      Significant therapeutic benefit has also been observed by the addition of
      sequential paclitaxel after adjuvant doxorubicin plus cyclophosphamide in
      operable breast cancer. Overall, more than 20 randomized studies with paclitaxel
      or docetaxel, either as single agents or in combination, are ongoing or planned
      in women with high-risk operable breast cancer. This massive effort is mainly
      based on empirical study designs. However, some preclinical characteristics of
      the taxanes, such as their increased antitumor effect in tumors overexpressing
      HER2/neu, the preclinical and clinical evidence of potential synergism with
      monoclonal antibodies directed against the HER2 receptor, and preclinical
      evidence of antiangiogenic properties should be pursued to test whether the use
      of taxanes in breast cancer could be tailored to individual tumor characteristics
      rather than following the usual pattern of indiscriminate application.

PMID- 9928569
TI  - Continuous infusional chemotherapy for early breast cancer: the Royal Marsden
      Hospital experience.
AB  - 5-FU is a cycle-specific S-phase-dependent drug with a short half life of 10-20
      min. There is therefore a rationale for its use in long-term continuous
      infusional therapy, with doses of up to 300 mg/m2 per day proving feasible for
      prolonged periods. The schedule is active in patients with heavily pre-treated
      breast cancer, with responses in up to 53% (overall 29%). At the Royal Marsden
      Hospital we have evaluated infusional 5-FU 200 mg/m2 per day for up to 6 months
      in combination with 3-weekly bolus epirubicin (E) 60 mg/m2 and cisplatin (C) 60
      mg/m2 (infusional ECF) as pre-operative/neo-adjuvant treatment in 123 patients
      with operable breast cancer greater than 3 cm (median 6 cm), initially in a phase
      II study of 50 patients and subsequently as part of a randomised phase III trial.
      One hundred and eighteen (96%) have achieved objective tumour responses, with 67
      (57%) achieving CR. The 5-year actuarial survival rate is 78% and the local
      recurrence rate without associated metastatic disease 12%. The pathological
      complete remission (CR) rate was 16%, with a further 5% having residual DCIS
      only. Pathological CR but not clinical CR is an independent predictor for disease
      fee survival. The Royal Marsden is now conducting two multicentre randomised
      trials of infusional ECF: (i) versus conventional AC (adriamycin
      cyclophosphamide) as pre-operative/neo-adjuvant chemotherapy, with 376 patients
      so far randomised towards a target of 400; and (ii), more recently, a similar
      adjuvant trial versus conventional FEC (5-FU, epirubicin, cyclophosphamide), with
      168 patients so far randomised. These trials will determine whether encouraging
      phase II activity with continuous infusional chemotherapy translates eventually
      into real survival benefit for patients with early breast cancer.

PMID- 9928570
TI  - Tailored chemotherapy to equal toxicity: is it possible?
AB  - Conventional dosage of chemotherapy based on body surface area in patients with
      normal organ functions will result in marked interindividual variations in
      systemic exposure to the cytostatics used. This will result in over- and
      undertreatment of the individual patient associated with unwarranted toxicity and
      suboptimal outcome. The intention to modify dosage is motivated by a possible
      correlation between toxicity and outcome. New dosage strategies with individual
      tailoring of the therapy should be investigated with the aim of increasing the
      efficacy of therapy without increasing its toxicity. Pharmacokinetic monitoring
      using the limited sampling procedure could be one alternative, another toxicity
      guided dosage. The dosage scheme used for tailored FEC polychemotherapy (six dose
      levels), based on therapy to equivalent haematological toxicity, has been
      clinically applicable in the multicentre setting for both adjuvant and
      preoperative therapy. In the adjuvant setting it has resulted in the delivery of
      significantly higher epirubicin and cyclophosphamide doses without increasing
      acute toxicity to the same extent; in two out of three patients no difference in
      acute toxicity could be verified for the highest two dose levels compared with
      the lower dose levels. In short, we could obtain better results with our present
      arsenal of cytostatics if we used them better.

PMID- 9928571
TI  - Anti-angiogenesis therapy and strategies for integrating it with adjuvant
      therapy.
AB  - Tumor angiogenesis is critical for the growth of primary cancers above 1-2 mm in
      diameter. A major vascular growth factor is VEGF, and approaches to inhibit VEGF
      have shown encouraging results in pre-clinical studies. The mechanisms involved
      in switching on angiogenesis involve activation of oncogenes and upregulation of
      the hypoxia-sensing pathway. These provide novel targets for therapy. Many anti
      angiogenic drugs are in clinical trial currently and there are problems in
      assessing these types of drugs if they only cause disease stabilisation. It will
      be important to develop methods to assess inhibition of vascular growth in vivo.
      New generations of anti-angiogenesis drugs such as endostatin of angiostatin,
      which are more potent, may cause tumor regression, but this has not yet been
      studied in patients. These approaches for advanced disease should be more
      successful when applied early in an adjuvant situation. This will also require
      careful monitoring of long-term toxicity.

PMID- 9928572
TI  - New developments in high-dose chemotherapy for breast cancer.
AB  - High-dose chemotherapy with autologous stem cell support as applied to the
      treatment of breast cancer has shown promise for over 15 years. Three main
      approaches have been used: (1) standard-dose induction chemotherapy followed by
      one or two cycles of myeloablative therapy, (2) multicycle nonablative
      combination chemotherapy, and (3) high-dose sequential chemotherapy using single
      agents at the maximum tolerated doses in rapid sequence. Each of these approaches
      has a strong biological rationale and is being pursued in randomized trials.
      Unfortunately, comparative data are limited and there is only one fully published
      randomized trial of the use of high-dose chemotherapy in metastatic breast
      cancer. This small study from South Africa showed a significant improvement in
      response rate and survival for women receiving high-dose chemotherapy compared to
      those given standard dose treatment. It is anticipated that results from larger
      studies in the USA and Europe evaluating the use of high-dose chemotherapy in
      metastatic breast cancer and in adjuvant treatment of poor-prognosis early-stage
      disease will be available within the next 2-3 years. A potentially important and
      related issue is that of tumor contamination of bone marrow and apheresis
      collections. Current data suggest that finding epithelial tumor cells with
      sensitive techniques (such as immunohistochemistry or polymerase chain reaction)
      gives prognostic information. However, it is not clear whether reinfusion of
      these cells after high-dose chemotherapy contributes to relapse of breast cancer.
      Unfortunately, understanding of the data is marred by a lack of standardization
      of assay methodology. Further work is needed to develop a widely accepted method
      for the detection of circulating tumor cells before the clinical relevance of
      such a finding can be meaningfully interpreted.

PMID- 9928573
TI  - Quality of life assessment in the adjuvant setting: is it relevant? International
      Breast Cancer Study Group.
AB  - In the breast cancer adjuvant therapy setting, the critical issue to consider in
      treatment decision-making is the tradeoff between quality and quantity of life.
      The toxicities of adjuvant therapies, both acute and late, must be balanced
      against the potential benefits of delayed recurrence and improved survival. The
      question should be addressed concerning when quality-of-life assessment is
      relevant in the adjuvant setting. Such assessments can inform patients about what
      to expect from their treatment, describe quality-of-life differences between
      treatments, provide an additional baseline measure with potential prognostic
      significance, inform clinicians about their patients' experiences with
      toxicities, indicate situations in which psychosocial interventions might be
      useful, and document patient adaptation to diagnosis and treatment. The relevance
      of quality-of-life assessment in the adjuvant setting can be illustrated by
      investigating one of the most controversial questions of today: When should
      chemotherapy be added to tamoxifen for postmenopausal patients? Data from the
      International Breast Cancer Study Group (IBCSG) Trial VII showed that adding 3
      months of CMF (cyclophosphamide 100 mg/m2 orally days 1-14; methotrexate 40 mg/m2
      i.v. days 1, 8; fluorouracil 600 mg/m2 i.v. days 1, 8; repeated every 28 days) to
      tamoxifen significantly improved disease-free survival compared with tamoxifen
      alone. The Quality-adjusted Time Without Symptoms of disease or Toxicity of
      treatment (QTWiST) method was used to compare the adjuvant therapies with respect
      to quality-adjusted survival. The analysis indicated that the decision to use
      adjuvant chemotherapy in this setting should be based on patient preferences
      concerning the relative importance of treatment toxicity versus disease
      recurrence.

PMID- 9928574
TI  - Quality of life assessment in the International Breast Cancer Study Group: past,
      present, and future.
AB  - The past: Since 1986, the IBCSG has been accruing a comprehensive longitudinal
      health-related quality of life (QL) database in addition to biomedical data of
      patients with early breast cancer who are receiving or have received adjuvant
      treatment. Our aim is to establish QL as a complementary outcome in randomized
      clinical trials and to gain new insight in biopsychosocial interactions. In
      regard to methodology, the IBCSG has made major contributions to the field
      through the development of global indicators, cross-cultural validation, impact
      of timing of assessments and working on practical and statistical issues relating
      to missing data. The present: In two large-scale clinical trials (IBCSG VI and
      VII) adjuvant chemotherapy (CMF) had a measurable effect on health-related QL,
      but contrary to expectations this effect was transient and minor compared with
      the effect of patients' adjustment and coping after diagnosis and surgery. THE
      FUTURE: In addition to the assessment of health-related QL, the IBCSG is
      currently developing and applying a global indicator for a patient-derived
      adapted utility concept in order to better assess the cost-benefit ratio of
      adjuvant treatment. However, the real challenge for the immediate future is the
      question how patients' adjustment can be fostered within primary care.

PMID- 9928575
TI  - Impact of different adjuvant therapy strategies on quality of life in breast
      cancer survivors.
AB  - Little is known about the long-term effects of adjuvant therapy on quality of
      life, sexual functioning and symptoms in breast cancer survivors. Between January
      1996 and June 1997, we surveyed 1098 women who had been diagnosed with early
      stage breast cancer between 1 and 5 years earlier. The breast cancer survivors
      were recruited in two large metropolitan centers in the USA. They completed a
      survey battery that contained standardized measures of health-related quality of
      life (HRQL), depression, body image, sexual functioning, and symptoms. A total of
      1096 had usable responses for these analyses. In this sample, n = 356 had
      received tamoxifen (TAM) alone, n = 180 received chemotherapy (CHEM) alone, n =
      395 received CHEM + TAM, and n = 265 received no adjuvant therapy (NO RX). There
      were significant differences in the mean age of each group, with the TAM group
      being the oldest (mean 62.6 years) and the CHEM group being the youngest (mean
      46.8 years). Both age and time since diagnosis were controlled for in all
      statistical analyses. We found no significant differences in global quality of
      life among the four treatment groups. For the MOS-SF-36, there were no
      significant differences on the subscale scores except for the physical
      functioning subscale (p = 0.0002); the NO RX group had the highest functioning.
      There were no significant differences in depression scores among the four
      treatment groups. The MOS-SF-36 physical functioning composite score differed by
      treatment group (p = 0.012); the NO RX group had a physical functioning composite
      score that was at the mean for a normal healthy population of women, while those
      in the adjuvant treatment groups scored slightly lower. The mental health
      composite score was not significantly different among the four treatment groups
      and approximated scores from the normal population of healthy women. There were
      no differences in body image scores among the four treatment groups; however,
      sexual functioning scores did differ (p = 0.0078) with patients receiving
      chemotherapy (either alone or with tamoxifen) experiencing more problems. Hot
      flashes, night sweats, and vaginal discharge differed by treatment (p = 0.0001);
      all symptoms were reported more often in breast cancer survivors on tamoxifen.
      Vaginal dryness and pain with intercourse also differed significantly by adjuvant
      treatment, occurring more often in survivors treated with chemotherapy. Overall,
      breast cancer survivors function at a high level, similar to healthy women
      without cancer. However, compared to survivors with no adjuvant therapy, those
      who received chemotherapy have significantly more sexual problems, and those
      treated with tamoxifen experience more vasomotor symptoms.

PMID- 9928576
TI  - North American Adjuvant Breast Cancer Trials.
AB  - The National Cancer Institutes in the United States and Canada sponsor
      Cooperative Groups to perform randomized trials in distinct subsets of patients
      with early breast cancer. In women with low-risk ductal carcinoma in situ (DCIS),
      ongoing studies are evaluating the role of adjuvant breast irradiation. For those
      with low-risk, node-negative invasive tumors, efforts have been directed to
      improving the efficacy of tamoxifen, while in high-risk patients the focus has
      been on improving chemotherapy. The roles of dose intensity and dose density have
      been evaluated at dose levels requiring either G-CSF or stem cells. More
      recently, the introduction of taxanes into adjuvant regimens has been a major
      area of investigation. Following treatment with doxorubicin-cyclophosphamide
      (AC), patients have been randomized to receive paclitaxel or no further therapy
      in INT 0148 and NSABP B-28 and to receive docetaxel in NSABP B-27. For women with
      4-9 involved nodes, sequential treatment A(doxorubicin)-T(paclitaxel)
      C(cyclophosphamide) with G-CSF is being compared to AC x 4 followed by high-dose
      chemotherapy with stem cell support. Cooperative Group trials have been critical
      in defining the standard of care in the past, and successful completion of these
      new trials is essential for further progress against breast cancer.

PMID- 9928577
TI  - International Breast Cancer Study Group trials.
AB  - The International Breast Cancer Study Group (IBCSG) was established in 1978 as
      the Ludwig Breast Cancer Study Group. It involved member institutions from
      Switzerland, Australia, New Zealand, Sweden, Italy, Slovenia, South Africa,
      Spain, Canada, Hong Kong and at various times from other countries. It has
      completed seven trials in three generations, and has a further eight trials
      currently open. Total accrual to December 1997 exceeds 12,000, and more than 9000
      of these patients are in active follow-up. Early trials established the pattern
      of addressing important biological questions and adapting the randomisation to
      the risk group of the patient. The first two generations of trials demonstrated
      that combined modality chemoendocrine therapy was superior to endocrine therapy
      alone or no therapy in node-positive postmenopausal patients; that a single
      perioperative cycle improved disease-free survival (DFS) in node-negative
      patients, but was inferior to more prolonged therapy in node-positive patients;
      and that six conventionally timed cycles of CMF were as effective as seven cycles
      commenced in the perioperative period. Recently reported trials in node-positive
      patients showed that three early cycles of CMF chemotherapy added to tamoxifen in
      postmenopausal patients, while late reintroduction of chemotherapy appeared
      detrimental, particularly in patients with ER-negative tumors. In premenopausal
      patients six initial cycles were superior to three, especially in younger
      patients. Current studies in node-positive patients are addressing the role of a
      gap between courses of different chemotherapy, and the relative value of the anti
      estrogens tamoxifen and toremifene. In node-negative premenopausal patients
      ovarian suppression with goserelin is being tested either instead of or added to
      CMF, while the value of initial CMF before tamoxifen is being tested in node
      negative postmenopausal patients. For high-risk patients a triple-transplant
      regimen is being compared with conventional dose therapy. Planning for future
      trials recognises the need for rapid accrual of large numbers of similar
      patients, and therefore the need for inter-Group collaboration. The emergence of
      the Breast International Group as a consortium of European, Australasian and
      Canadian cooperative Groups is important to the rapid evaluation of new agents
      and strategies.

PMID- 9928579
TI  - The EORTC-Breast Cancer Cooperative Group clinical research programme in early
      breast cancer. EORTC-BCCG.
AB  - The aims of the European Organization for Research and Treatment of Cancer
      (EORTC) are to conduct, develop, coordinate, and stimulate research in Europe on
      the experimental and clinical bases of cancer treatment. Along these lines, the
      EORTC Breast Cancer Cooperative Group, which belongs to the EORTC treatment
      division, aims at improving the standard of early and advanced breast cancer
      treatment in Europe through the conduct of large, prospective, randomized,
      multicenter cancer clinical trials investigating innovative approaches as well as
      relevant questions regarding optimal surgery and radiotherapy or the optimal
      integration of these various treatment modalities. This paper reviews the current
      clinical research programme of this group in the field of "early" breast cancer
      and briefly alludes to the ongoing efforts of the group in areas such as quality
      control and translational research. Finally, the EORTC-BCCG has been instrumental
      in the foundation of the Breast International Group, "BIG", which is a large
      "intergroup" of existing European and Australian breast cancer research groups.
      It is hoped that BIG will accelerate the turnover of sufficiently large and well
      designed breast cancer adjuvant clinical trials through increasing cooperation
      between its group members as well as collaboration, whenever indicated, with the
      American Breast Cancer Intergroup.

PMID- 9928578
TI  - Nordic trials of adjuvant therapy in primary breast cancer.
AB  - The Scandinavian Breast Group (SBG), established in 1989, has members
      representing research, diagnosis, and treatment of breast cancer. In 1992 the SBG
      analyzed ongoing adjuvant trials in the Scandinavian countries. Many trials were
      analyzing similar questions, but a substantial proportion recruited an
      insufficient number of patients to enable valid conclusions within a reasonable
      time. As a result the SBG Clinical Trials Group was established to coordinate and
      organize trials in primary and advanced disease. Present activities include a
      study in premenopausal patients with node-positive, receptor-positive disease
      (CMF vs castration), a study in pre- and postmenopausal patients with node
      positive, receptor-negative disease (CMF vs CEF), and a study in high-risk
      patients aged < 60 years (dose-escalating CEF vs three cycles of CEF followed by
      high-dose chemotherapy and autologous stem cell support). All these studies are
      planned to close during 1998. Another study has recently been activated. This
      enrolls patients with climacteric symptoms given previous treatment for in situ
      or invasive breast cancer, who are randomized to observation vs hormone
      replacement therapy for 2 years. Other groups are strongly encouraged to
      participate. Potential future activities are briefly described. Some of these
      will be undertaken in international collaboration.

PMID- 9928580
TI  - Italian Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group Trials.
      GROCTA Trials.
AB  - The first GROCTA trial compared 5-year tamoxifen treatment to ten chemotherapy
      cycles in a group of 504 pre-/post-menopausal, node-positive, ER-positive breast
      cancer patients. This study also included an arm combining tamoxifen with
      chemotherapy. Fifteen-year results showed no difference between tamoxifen and
      tamoxifen plus chemotherapy, while both treatments were significantly superior to
      chemotherapy alone. A confirmatory study (GROCTA 02) was performed in 244 pre
      /perimenopausal patients by comparing 5 years of tamoxifen treatment (plus 2
      years of goserelin) to six CMF cycles. No difference has emerged so far between
      the tamoxifen and CMF arms at a median follow-up time of 62 months. Post
      menopausal women were scheduled to receive 3 years of tamoxifen treatment and
      then to be randomly allocated to further 2 years of tamoxifen or to 2 years of
      low-dose aminoglutethimide (GROCTA 04B). So far 662 patients have been entered,
      375 of whom have been randomized to tamoxifen (n = 188) or aminoglutethimide (n =
      187). Preliminary results (median follow-up time 32 months) show no major
      difference in patients' outcome. A new trial (ITA trial) with a similar design
      but employing anastrozole in place of aminoglutethimide has been activated in
      1998. The GROCTA 03 study investigated the potential superiority of alternating
      adjuvant chemotherapy over standard CMF. This study, which included 107 node
      positive ER-negative pre-menopausal women, was prematurely closed because more
      patients allocated to the triple alternated chemotherapy appeared to have
      relapsed and died at the first interim analysis. The use of high-dose
      chemotherapy (HDC) was explored by the GROCTA 06 trial which included 53 patients
      with ten or more involved nodes and a maximum age of 55 years. These patients
      were scheduled to receive three standard CEF cycles followed by one cycle of HDC
      (cyclophosphamide 5 g/m2; etoposide 1.5 g/m2; cisplatin 150 mg/m2) without any
      form of bone marrow rescue. This HDC program proved to be feasible but was not
      superior to CMF-based chemotherapy we had previously employed in a comparable
      group of patients in previous GROCTA trials. These findings prompted us to
      explore new HDC programmes with the use of peripheral stem cell support and in
      addition the possible value of new drugs such as Taxol and vinorelbine. New
      generation trials will also explore the value of new prognostic indicators such
      as tumor proliferative activity, which are prospectively used to allocate
      patients to different treatment options.

PMID- 9928581
TI  - Current trials of the German Adjuvant Breast Cancer Group (GABG).
AB  - Since 1981 the German Adjuvant Breast Cancer Study Group (GABG) has recruited
      approximately 5000 patients with primary breast cancer in randomized trials to
      evaluate systemic therapies. More than 70 hospitals all over Germany are
      participating in this group. Allocation to the different trials is based on a
      risk-oriented selection of patients (menopausal status, nodal involvement and
      hormonal receptor content). In the currently running trials chemo-endocrine or
      endocrine-endocrine sequences are investigated. In premenopausal patients the
      value of GnRH analogues are compared with conventional CMF chemotherapy. The aim
      of two further trials is to reduce local surgery or radiotherapy in patients with
      low risk for locoregional relapse. In a recently started study dose-intensified
      preoperative chemotherapy in combination with or without tamoxifen is evaluated
      in patients with operable breast tumors > or = 3 cm.

PMID- 9928582
TI  - International Consensus Panel on the treatment of primary breast cancer. V:
      Update 1998.

PMID- 9928583
TI  - Using outcomes data to compare plans, networks, and providers: what is the state
      of the art?

PMID- 9928584
TI  - Accreditation and globalization.

PMID- 9928585
TI  - Hospital accreditation as a means of achieving international quality standards in
      health.

PMID- 9928586
TI  - Using health outcomes data to compare plans, networks and providers.
AB  - PURPOSE: To analyze the challenge of using health outcomes data to compare plans,
      networks and providers. ANALYSIS: Different questions require different designs
      for collecting and interpreting health outcomes data. When evaluating
      effectiveness of treatments, tests or other technologies, the question is what
      processes improve health outcomes? For this purpose, the strongest evidence comes
      from a double-blind randomized controlled trial. In program evaluations, the
      question is 'what is the impact of this policy and related programs on health
      outcomes?' For this purpose, we may be able to randomize subjects, but are more
      likely to have a quasi-experimental or an epidemiological design. When we compare
      plans, networks and providers for quality improvement purposes the question is
      'do these specific plans perform differently from one another?', or, 'are these
      specific plans improving their performance over time?' We want to isolate for
      study the effects attributable to specific plans. Designs that yield strong
      evidence cannot be applied because we lack experimental control. CONCLUSIONS:
      When we already have strong evidence linking specific processes of care with
      specific outcomes, comparing process data may reveal more about performance of
      plans, networks and providers than comparing outcomes data. Comparisons of
      process data are easier to interpret and more sensitive to small differences than
      comparisons of outcomes data. Outcomes data are most useful for tracking care
      given by high volume providers over long periods of time, targeting areas for
      quality improvement and for detecting problems in implementation of processes of
      care.

PMID- 9928587
TI  - The outcomes utility index: will outcomes data tell us what we want to know?
AB  - PURPOSE: To propose an approach to the evaluation of the utility of an outcome
      measure for use in making comparisons among health plans, hospitals, networks, or
      other accountable entities. METHOD: Seven components are recommended for
      evaluation: whether the outcome is a health outcome; the extent to which
      expectations for performance can be defined; the role medical care plays in
      achieving the outcome; the relative complexity of events that produce the
      outcome; the degree to which attribution can reasonably be made; the suitability
      of risk adjustment for limiting external sources of variation; and the likelihood
      that the measure provides perverse behavioral incentives. RESULTS: Illustrative
      examples are given in each area for scoring the performance of measures on the
      component. CONCLUSION: Outcomes measurement is of great interest to a variety of
      potential users. The approach proposed here is intended to provoke discussion and
      more rigorous development of tools that will help to identify the measures that
      are likely to produce the most useful information for making comparisons among
      accountable entities in the health system.

PMID- 9928588
TI  - Laboratory values improve predictions of hospital mortality.
AB  - OBJECTIVE: To compare the precision of risk adjustment in the measurement of
      mortality rates using: (i) data in hospitals' electronic discharge abstracts,
      including data elements that distinguish between comorbidities and complications;
      (ii) these data plus laboratory values; and (iii) these data plus laboratory
      values and other clinical data abstracted from medical records. DESIGN:
      Retrospective cohort study. SETTING: Twenty-two acute care hospitals in St Louis,
      Missouri, USA. STUDY PARTICIPANTS: Patients hospitalized in 1995 with acute
      myocardial infarction, congestive heart failure, or pneumonia (n = 5966). MAIN
      OUTCOME MEASURES: Each patient's probability of death calculated using:
      administrative data that designated all secondary diagnoses present on admission
      (administrative models); administrative data and laboratory values (laboratory
      models); and administrative data, laboratory values, and abstracted clinical
      information (clinical models). All data were abstracted from medical records.
      RESULTS: Administrative models (average area under receiver operating
      characteristic curve=0.834) did not predict death as well as did clinical models
      (average area under receiver operating characteristic curve=0.875). Adding
      laboratory values to administrative data improved predictions of death (average
      area under receiver operating characteristic curve=0.860). Adding laboratory data
      to administrative data improved its average correlation of patient-level
      predicted values with those of the clinical model from r=0.86 to r=0.95 and
      improved the average correlation of hospital-level predicted values with those of
      the clinical model from r=0.94 for the administrative model to r=0.98 for the
      laboratory model. CONCLUSIONS: In the conditions studied, predictions of
      inpatient mortality improved noticeably when laboratory values (sometimes
      available electronically) were combined with administrative data that included
      only those secondary diagnoses present on admission (i.e. comorbidities).
      Additional clinical data contribute little more to predictive power.

PMID- 9928589
TI  - Use of outcome data by purchasers and consumers: new strategies and new dilemmas.
AB  - OBJECTIVE: The complexities involved in measuring outcomes of care are perceived
      as a core challenge of health services research. However, the complexities
      associated with making outcomes data useable for purchasers and consumers are
      just beginning to be recognized. The purpose of this paper is to outline some of
      the barriers to purchaser and consumer use of clinical outcome (and other
      performance) data and to identify strategies for supporting greater use of these
      data. Dilemmas associated with current and proposed strategies are highlighted
      and recommendations are proposed. EVIDENCE: Three recent studies focusing on
      consumer and purchaser use of outcome data are used to illustrate barriers. The
      decision research literature is also drawn upon to describe the information
      processing challenges faced by purchasers and consumers when using performance
      information for making choices. FINDINGS: Information packaging strategies and
      decision support tools designed to overcome barriers are described, and dilemmas
      associated with their use are outlined. One major concern is that if we adopt
      strategies to make report card data more digestible, we may be trading off some
      of the market effects (e.g. improved health plan performance) that justify report
      card efforts in the first place.

PMID- 9928590
TI  - The Quality of Well-Being Scale: critical similarities and differences with SF
      36.
AB  - PURPOSE: To summarize the development and application of a generic measure of
      health-related quality of life known as the Quality of Well-Being Scale (QWB).
      BACKGROUND: The QWB is part of a general health policy model. The measure
      includes functional components for mobility, physical activity, and social
      activity. In addition, it includes a comprehensive list of symptoms and problems.
      QWB scoring allows placement of each individual on a continuum of wellness
      ranging from 0 (for dead) to 1.0 for asymptomatic full function. The General
      Health Policy Model combines this point in time measure with information on
      prognosis and mortality to estimate quality-adjusted life-years (QALYs). Forming
      a ratio of program costs to QALYs yields estimates of cost per quality-adjusted
      life year. Evidence supports the validity of the QWB for a wide variety of
      applications in population monitoring, descriptive studies of patient
      populations, and clinical trials. We offer a variety of comparisons between the
      QWB and Medical Outcomes Study Short Form 36 (SF-36). MAIN FINDINGS: In
      comparison with the SF-36, the QWB provides less information on health profiles,
      but has the advantage of providing a metric that can be used for cost-utility or
      cost-effectiveness analysis. Although ceiling effects are common for some SF-36
      subscales, perfect scores on the QWB are very rare. The QWB has an approximately
      normal distribution for populations of adults. Although, often criticized for not
      including a mental health component, we present evidence documenting the validity
      of the QWB for patients with psychological and psychiatric diagnoses.
      CONCLUSIONS: The QWB and SF-36 are alternative comprehensive measures of health
      outcomes.

PMID- 9928591
TI  - Anticipating market demand: tracking enrollee satisfaction and health over time.
AB  - OBJECTIVE: To assess guidelines, set by the National Committee for Quality
      Assurance, for the Health Plan Employer Data and Information Set (HEDIS) 1999
      CAHPS 2.0H Survey (formerly the HEDIS 1999 Consumer Survey) in the light of
      user's needs to monitor health plan performance over time, monitor sick
      enrollees, and prioritize determinants (drivers) of enrollee experience. DESIGN:
      A two-wave, cross-sectional/longitudinal panel design, consisting of national
      surveys mailed to employees of three major USA corporations in 1993 and 1995.
      STUDY PARTICIPANTS: Samples included employees selected to represent 23 major
      managed care and indemnity plans in five regions of the USA. In 1993, 14 587
      employees responded and in 1995 9018 employees responded (response rates: 51 and
      52%). The longitudinal panel sample included 5729 employees who completed both
      surveys and stayed in the same plan for both years. STUDY MEASURES: The main 1993
      and 1995 surveys consisted of 154 and 116 items, respectively. Panel survey
      content assessed care delivery, plan administration, functional status, well
      being, and chronic disease. RESULTS: CAHPS 2.0H's point-in-time, cross-sectional
      design was unable to detect selection bias and led to an inaccurate view of
      change in performance. CAHPS 2.0H's use of aggregate samples masked key
      differences between healthy and sick enrollees; e.g. the sick became less
      satisfied over time. The association-based, statistical techniques that many
      survey users will employ to prioritize the 'drivers' of enrollee experience in
      the absence of CAHPS 2.0H guidelines yielded a less efficient account of change
      than the multi-method/multi-trait approach developed for this project.
      CONCLUSION: Consumer experience of plan performance is best understood when the
      separate contributions of longitudinal membership and movement in and out of
      plans are clarified, changes in health are identified, changes for sick and
      healthy enrollees are compared, and plan performance on satisfaction criteria is
      probed to give confirmation and detail. Changes to the CAHPS 2.0H approach in
      HEDIS 1999 will facilitate user application of these principles.

PMID- 9928592
TI  - Building health plan databases to risk adjust outcomes and payments.
AB  - OBJECTIVES: To highlight the types and sources of data on medical risk and
      outcomes routinely collected by managed care organizations over time; to
      summarize the quality and consistency of these data; and to describe some of the
      difficulties that arise in collecting, pooling, and using these data. DESIGN:
      Synthesis of the experiences of two risk-adjustment modeling projects in
      assembling large volumes of demographic, diagnostic, and expense data from
      several health maintenance organizations (HMOs) over multiple years. SETTING: Six
      large HMOs from the Northwest, North Central, and Northeast regions of the USA.
      INTERVENTIONS: Health plans were approached to participate in a risk-adjustment
      study, presented with an extensive variable-by-variable data request, and, if
      willing to participate, asked to specify a desired process for extracting,
      copying, and transferring selected variables to the study site for purposes of
      research. Depending on local circumstances, three different approaches were used:
      (i) health plan staff obtained the data and organized them into the requested
      study format; (ii) study staff were provided access to health plan data systems
      to perform the extractions directly; and (iii) health plans hired contract
      programmers to perform the extractions under the direction of the study team. Key
      measures of risk and cost were extracted and merged into analysis files. MAIN
      OUTCOME MEASURES: Complete and consistent eligibility maps, demographic
      information, inpatient and outpatient diagnoses, and total health plan expense
      for each enrollee. RESULTS: We have been successful in collecting and integrating
      complete utilization, morbidity, demographic, and cost data on total memberships
      of five large HMOs as well as a subset from a sixth HMO, all for multiple years.
      CONCLUSION: While HMOs vary greatly in the quality and comprehensiveness of their
      data systems, these attributes have been improving across the board over time.
      Automated health plan data systems represent potentially valuable sources of data
      on health risks and outcomes and can be used to benchmark disease management
      programs and risk adjust capitation payments and medical outcomes.

PMID- 9928593
TI  - Accountability for health outcomes and the proper unit of analysis: what do the
      experts think?
AB  - BACKGROUND: An invitational conference was held in Dearborn, MI, in April of 1998
      to discuss technical and conceptual issues related to the general topic of using
      outcomes data to compare plans, networks, and providers. Approximately 150
      researchers, clinicians, purchasers, and representatives of accreditation bodies
      and government agencies attended. SURVEY OF PARTICIPANTS: At the opening session,
      attendees participated in an electronic survey exercise designed to identify
      areas of agreement or disagreement on controversial issues related to the main
      conference topic. MAIN FINDINGS: There was general agreement about the basic
      concept of health plan and provider accountability for health outcomes, and about
      the need for further development of data sources and case-mix adjustment models.
      There was disagreement about other issues, including questions of who should bear
      the cost of collecting outcomes data and whether results should be analyzed at
      health plan, network, or individual clinician level. CONCLUSION: A group of
      experts agreed on the importance of reporting comparative outcomes data, but
      disagreed on many of the technical details of how that could best be done.

PMID- 9928594
TI  - A major employer as a health care services laboratory.
AB  - Health care management within the USA operations of the Ford Motor Company is a
      substantial and critical enterprise. The company provides health care coverage
      for a population of 636,000 active employees, retirees and their dependents at a
      cost of US$1.5 billion annually. The company realizes that effective management
      of health care resources requires continuous improvement in the services for
      which the company contracts and in the manner in which these services are
      provided to employees. In this context, the company's health care management
      department views the Ford employee population as a living health care sciences
      laboratory for the design, evaluation and improvement of health care services.
      The population, available data sources, and their advantages and disadvantages
      for use in the evaluation of disease and health utilization patterns are
      discussed in this paper from an epidemiological perspective. Two examples of
      preliminary evaluations are presented to illustrate use of data from this large
      employee population for improving care provided to persons with elevated risk of
      cardiovascular disease.

PMID- 9928595
TI  - Effective reports for health care quality data: lessons from a CAHPS
      demonstration in Washington State.

PMID- 9928596
TI  - Delayed diagnosis of breast cancer.

PMID- 9928597
TI  - Charles Roy Henderson, 1911-1989: a brief biography.

PMID- 9928598
TI  - Influence of mating frequency on sow reproductive performance.
AB  - Gilts and sows were bred one, two, or three times during a single estrous period
      in a commercial herd for evaluating the effect of mating frequency on
      reproductive performance. Estrus detection started at approximately 0630 daily by
      applying back pressure to females with the presence of a mature boar. Natural
      mating was used. Gilts detected in estrus were mated in the morning of d 1 (AM),
      the morning of d 1 and 2 (AM-AM), and the morning and afternoon of d 1 and
      morning of d 2 (AM-PM-AM) for mating frequencies 1, 2, and 3, respectively. Sows
      were bred in the AM, AM-AM, AM-PM-AM (1), and morning of d 1 and morning and
      afternoon of d 2 [AM-AM-PM (2)] for mating frequency 1, 2, 3 (1), and 3 (2),
      respectively. Breeding events in the morning and afternoon started at
      approximately 0730 and 1530. Females were randomly assigned to a mating
      frequency. Boars were randomly assigned to each breeding event. In total, 256
      gilts and 766 sows were involved in the study. Gilts with a single mating (76.5%,
      P = .06) and triple matings (80.4%, P < .05) had higher farrowing rates than
      those with double matings (65.3%). No differences (P > .1) in the farrowing rates
      of sows were observed between mating frequencies 1, 2, 3 (1), and 3 (2). Double
      mated gilts had more (P < .03) total born (9.7 vs 8.6) and pigs born alive (9.3
      vs 8.2) than did single-mated gilts. There were no differences (P > .3) in total
      born and pigs born alive in sows between mating frequencies. We concluded that
      triple-mating gilts and sows did not improve farrowing rate and litter size
      compared with single and double matings. There were no differences in farrowing
      rate and litter size between double- and single-mated sows. Gilts with double
      matings had a larger litter size than those with a single mating.

PMID- 9928599
TI  - Preweaning growth traits for Senepol, Hereford, and reciprocal crossbred calves
      and feedlot performance and carcass characteristics of steers.
AB  - We conducted a multiyear study in two phases to determine preweaning performance
      traits of Senepol (S x S), Hereford (H x H), and reciprocal (S x H and H x S) F1
      crossbred calves and feedlot performance and carcass characteristics of steers.
      In Phase I, from 1985 to 1989, data from S x S (n = 194), H x H (n = 383), and S
      x H (n = 120) calves were used. Numbers of S x S cows were increased during Phase
      I so that data from H x S (n = 74) calves could be included in Phase II (1990 to
      1992) in addition to S x S (n = 118), H x H (n = 130), and S x H (n = 56) calves.
      Also during Phase II, feedlot performance and carcass characteristics were
      determined for S x S (n = 30), H x H (n = 26), H x S (n = 36), and S x H (n = 26)
      steers. In Phase I, S x S calves had heavier (P < .01) birth weights and heavier
      (P < .01) 205-d adjusted weaning weights than H x H calves. Birth weights of S x
      H calves were heavier (P < .01) than the mean of the purebred calves, but 205-d
      adjusted weaning weights did not differ (P > .10). In phase II, direct heterosis
      was 3.5% for birth weight (P < .05) and 5.1% for 205-d adjusted weaning weight (P
      < .01). Senepol maternal breed effects were 1.9 kg for birth weight (P < .10) and
      37.9 kg for 205-d adjusted weaning weight (P < .01). Levels of direct heterosis,
      Senepol maternal breed effects, and Hereford direct breed effects were
      significant for most feedlot performance traits of steer calves that were fed to
      a common end point. Breeds did not differ (P > .10) for USDA yield and quality
      grades, and direct heterosis was not significant for Warner-Bratzler shear force.
      These results demonstrate significant levels of heterosis in preweaning
      performance between S x S and H x H calves and in feedlot performance of steers.
      Levels of heterosis were smaller and nonsignificant for most carcass traits
      including meat tenderness, which did not differ between S x S and H x H steers in
      this study.

PMID- 9928600
TI  - Recycled cafeteria food waste as a feed for swine: nutrient content
      digestibility, growth, and meat quality.
AB  - This project was undertaken to compare growth, meat quality, and diet
      digestibility when pigs were fed cafeteria food waste (FW) or a corn/soybean meal
      (CSM) diet. Cafeteria food waste (36 samples) fed in the growing and finishing
      experiment averaged 22.4% DM, 21.4% CP, 14.1% ADF, 27.2% ether extract, and 3.2%
      ash. The first experiment used 50 crossbred pigs randomly assigned to four diets.
      During the growing phase, pigs fed a CSM diet gained faster (P < .05) than pigs
      fed FW or FW plus energy supplements. However, the two groups fed FW plus energy
      supplements (at 25 or 50% of the intake of the CSM diet) gained faster (P < .05)
      than pigs fed FW alone (.61 and .65 kg/d, respectively, vs .46 kg/d). In the
      finishing phase, FW plus an energy supplement fed at 50% of the level of CSM
      intake resulted in gains that did not differ from those of pigs fed the CSM diet
      (.90 vs .99 kg/d; P > .05). A nutrient digestibility and nitrogen balance trial
      using eight growing barrows compared FW with the same CSM growing diet fed
      earlier. Dry matter digestibility was similar for the two diets (P > .05).
      However, CP digestibility was higher (P < .05) in the FW diet than in the CSM
      diet (88.2 vs 84.3%). Although the percentage of nitrogen retained was not
      different between FW and CSM diets (56.0 vs 55.2%; P > .05), the amount of
      nitrogen retained was greater for pigs fed the CSM diet (29.3 vs. 24.5 g/d; P <
      .05) because DMI was greater (1.7 vs 1.4 kg/d) for pigs fed CSM compared with FW.
      At the completion of the finishing experiment, six pigs were selected from both
      the CSM and FW diets and fed to finishing weight. The pigs were slaughtered, and
      the pork loins were removed for flavor and texture analysis. A consumer panel
      rated the meat quality from FW pigs as acceptable and overall flavor comparable
      to CSM pigs (P > .05). These results indicate that food waste has nutritive value
      and may be useful in swine diets.

PMID- 9928601
TI  - Effects of feeding combinations of steam-flaked grain sorghum and steam-flaked,
      high-moisture, or dry-rolled corn on growth performance and carcass
      characteristics in feedlot cattle.
AB  - The objective of these two feeding trials was to determine the associative
      effects of feeding steam-flaked grain sorghum (SFGS) in combination with steam
      flaked (SFC), dry-rolled (DRC), or high-moisture (HMC) corn on growth performance
      and carcass characteristics in feedlot cattle. In Trial 1, 200 yearling heifers
      were blocked by weight, allotted to 25 pens, and fed one of five finishing diets
      (77% grain, 15% corn silage, and 8% supplement on a DM basis) for an average of
      137 d. The grain combinations were 100:0, 75:25, 50:50, 25:75, and 0:100
      SFC:SFGS, respectively. Treatment had no effect on DMI (P > .05), but ADG, gain
      efficiency, and final live and hot carcass weights decreased linearly (P < .05)
      as the proportion of SFGS increased in the diet. Carcass backfat, quality grade,
      and liver abscess score were not affected (P > .05) by treatment. In Trial 2, 306
      yearling steers were blocked by weight, allotted to 30 pens, and fed diets that
      contained 74.5% grain, 10% corn silage, 7.5% soybean meal, 4% tallow, and 4%
      supplement (DM basis) for an average of 139 d. The grain and grain combinations
      were 100% DRC, HMC, SFC, or SFGS and a 67%:33% combination of SFGS: DRC or
      SFGS:HMC. For steers fed diets containing a single source of grain, those fed SFC
      gained 7% more live weight and had a 7% higher gain efficiency (P < .05) than
      those fed DRC or HMC. Growth performance of steers fed SFGS was intermediate.
      Feeding grain combinations (67% SFGS:33% HMC or DRC) resulted in a 5 to 6%
      positive associative effect (P < .05) for ADG and gain efficiency. Carcass
      characteristics were not affected (P > .05) by treatment. We concluded that there
      were significant benefits (positive associative effects) when SFGS was fed in
      combination with DRC or HMC, but the effects were smaller when SFGS was fed in
      combination with SFC.

PMID- 9928602
TI  - Agricultural sciences and education in the 21st century.
AB  - Rapid, ever-accelerating changes in science and technology will make current
      educational knowledge and systems obsolete as quickly as we reinvent them.
      Changes in demographics in our nation and changes in international trade will
      require us to encourage participation by all Americans, regardless of race or
      gender. Historically, change in higher education has faced strong resistance, but
      the establishment of the Land-Grant University system, the G.I. Bill, and other
      changes have encouraged participation by new groups of Americans. In order to
      take full advantage of all of the talent necessary to address the needs of a
      changing world, animal science departments and agricultural colleges must seek
      new partnerships to enhance recruitment of people from diverse groups, ensure
      that courses and curricula address the future, and encourage and promote women
      and minority faculty. Members of the American Society of Animal Science should
      continue to lead such changes.

PMID- 9928603
TI  - The effect of farrowing crate heat lamp location on sow and pig patterns of lying
      and pig survival.
AB  - Three experiments were conducted to study sow and pig behavior during the 1st 3 d
      after birth and pig survival during the 1st 2 wk after farrowing. In Exp. 1, 23
      sows were housed in conventional farrowing crates that were divided into five
      sections: a .5- x 1.5-m front creep section and the remaining area divided into
      four sections, .75 x 1.05 m each. Air temperature was maintained at 19 degrees C,
      and a 250-W heat lamp was placed at the right side of the front creep in
      Treatment 1 (T1), or in the creep at the right side of the sow for Treatment 2
      (T2). The percentage of pigs within 8 cm of the sow's trunk was not affected by
      treatment, but it decreased (P < .001) from 61.8 +/- 3.4% on d 1 to 28.1 +/- 3.5%
      on d 3. As the percentage of pigs near the sow decreased, the percentage of pigs
      within the section containing the heat lamp increased (T1, P < .05; T2, P < .10).
      Experiment 2 involved 15 sows and litters housed as in Exp. 1, except that heat
      lamps were not provided, and average air temperature was 27.3 +/- .2 degrees C
      during behavioral observations. Even though the portion of the litter near the
      sow decreased (P < .001) from d 1 to d 3 (d 1, 57.0 +/- 3.4%; d 2, 42.9 +/- 3.3%;
      d 3, 31.7 +/- 3.3%), pigs did not concentrate in any specific section as they
      moved away from the sow. The average number of pigs within the front creep
      section (Section 1) for the 3-d period was less than (P < .01) the number in any
      other crate section. Experiment 3 involved 147 sows and tested the effect of
      solid creep floor covering on pig survival for each of the heat lamp locations
      used in Exp. 1. Neither heat lamp location nor floor covering affected pig
      survival. During the 1st 3 d of life, pigs tend to lie near the sow regardless of
      heat lamp location or air temperature. Heat lamp position and floor covering
      under the lamp do not affect pig survival.

PMID- 9928604
TI  - Feeding colostrum increases circulating insulin-like growth factor I in newborn
      pigs independent of endogenous growth hormone secretion.
AB  - Our objective was to examine the influence of feeding and endogenous GH secretion
      on circulating IGF-I in colostrum-deprived newborn pigs fed colostrum (n = 4),
      formula (control, n = 4), or water (n = 4). In another four formula-fed pigs, GH
      was ablated (GRF-A) with two intravenous injections of a GH releasing-factor
      antagonist (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2. Blood was serially sampled in all
      pigs to measure plasma IGF-I and GH profiles. Feeding increased plasma IGF-I
      concentration two- to fourfold and decreased GH secretion. Despite a more than
      80% decrease in the plasma GH in GRF-A pigs, the circulating IGF-I concentration
      was similar to that in control pigs. In colostrum-fed pigs, plasma IGF-I was
      higher than that in control pigs, despite equal nutrient intake and lower
      circulating GH. There were no differences in plasma IGF binding protein (IGFBP)-3
      levels among the treatment groups. However, the relative abundance of plasma
      IGFBP-4 was lower, and that of IGFBP-1 higher, in unfed pigs than in any of the
      three fed groups. The plasma insulin concentration was not different among fed
      pigs, but it was lower in unfed pigs. Our results indicate that the circulating
      IGF-I concentration is more dependent on nutrient intake than on GH in newborn
      pigs, despite relatively high GH concentrations. However, because the nutrient
      content in the formula was designed to match that of colostrum, a factor other
      than nutrient intake and GH was responsible for the maximal increase in
      circulating IGF-I concentration observed in colostrum-fed pigs.

PMID- 9928605
TI  - Can pale, soft, exudative pork be prevented by postmortem sodium bicarbonate
      injection?
AB  - Previous attempts at eliminating the problem of PSE pork by genetic selection or
      rapid postmortem cooling have been only partially successful. A new approach,
      namely, postmortem injection of sodium bicarbonate (SBC), was tested on halothane
      positive gilts. Sixteen pigs were used to establish a suitable SBC concentration.
      At approximately 15 min after death, the longissimus of one side of the carcass
      was injected with 10% (by weight) of .2 to .4 M SBC solutions containing .7% NaCl
      (wt/vol). All concentrations resulted in a higher ultimate pH, improved muscle
      color, and reduced drip loss. In a second experiment, with 23 pigs, .3 M SBC was
      injected into the longissimus and the biceps femoris at either 15 min or 24 h
      after death and with or without inclusion of .7% NaCl (wt/vol). Compared with
      controls, the 15-min SBC + NaCl injected samples had darker color (L* of 47 vs 53
      in controls), higher ultimate pH (5.6 vs 5.3), lower drip loss (5% vs 10%), and
      increased protein solubility (140 vs 115 mg/g). Injection at 24 h reduced drip
      loss (from 10% to 5.7%) but did not correct the color defect. The SBC alone and
      SBC + NaCl treatments had essentially the same effects in reducing drip loss,
      increasing ultimate pH, and improving color; but the SBC-NaCl injected samples
      had improved juiciness and flavor compared with SBC. Early postmortem sodium
      bicarbonate injection seems to prevent the development of PSE pork when injected
      into carcasses of halothane-sensitive pigs.

PMID- 9928606
TI  - The energetic value of nonstarch polysaccharides in relation to physical activity
      in group-housed, growing pigs.
AB  - The dose response effect of dietary nonstarch polysaccharide (NSP) content on
      physical activity in relation to metabolic rate in pigs was studied. Twelve
      clusters of 14 pigs (50-kg castrated males) were fed one of four diets, similar
      in composition, except for the starch and NSP content. The difference in starch
      and NSP ratio was created by exchanging sugar beet pulp silage (SBPS) for
      tapioca. On a DM basis, diets contained 0, 5, 10, or 15% SBPS. Pigs were housed
      in groups and fed at 2.5 times the maintenance energy requirements. Nitrogen and
      energy balances were measured per cluster during a 7-d experimental period, which
      was preceded by a 2-wk adaptation period. Dietary composition did not affect ADG.
      Metabolizability decreased with increasing dietary SBPS content (P < .01). Heat
      production as well as energy retention were unaffected by the exchange of starch
      for NSP (P > .1). However, dietary composition affected energy expenditure on
      physical activity (P < .10). Pigs were more quiet when dietary NSP content
      increased. Based on heat production data and on apparent digestibility of crude
      protein, crude fat, and NSP, the estimated net energy value of fermented NSP was
      14.8 kJ/g. This relatively high energy value of fermented NSP was mainly related
      to the lowered energy expenditure for physical activity, 3.9 kJ/g of fermented
      NSP. The present study demonstrated that the lower energetic utilization of
      fermented NSP compared with that of starch can be fully compensated in pigs by
      reducing their physical activity. Thus, energy evaluation systems should account
      for systematic dietary influences on physical activity.

PMID- 9928607
TI  - Evaluation of potato proteins on the growth performance of early-weaned pigs.
AB  - We conducted five experiments to evaluate conventional and low-glycoalkaloid
      potato protein (CPP and LGPP, respectively) in diets for early-weaned pigs. In
      Exp. 1, 150 weanling pigs (initially 4.4 +/- .9 kg and 15.5 +/- 2 d of age) were
      fed either a control diet containing 3% spray-dried animal plasma (SDAP) or diets
      with additional SDAP (2.5 or 5% added; 5.5 or 8% total) or CPP (2.6% or 5.1%)
      substituted on a total lysine basis. From d 0 to 14 after weaning, increasing
      SDAP increased (linear, P < .05) ADG and ADFI, whereas increasing CCP had no
      effect on growth performance. In Exp. 2, 180 weanling pigs (initially 5.9 +/- 1.2
      kg and 20 +/- 2 d of age) were fed diets containing a LGPP replacing 25, 50, 75,
      or 100% of the 7% dietary SDAP on a digestible lysine basis. From d 0 to 7 after
      weaning, increasing LGPP increased and then returned to control levels ADG and
      ADFI (quadratic, P < .01) and gain:feed ratio (quadratic, P < .05). In Exp. 3,
      175 weanling pigs (initially 5.5 +/- 1.1 kg and 20 +/- 3 d of age) were fed
      either a control diet containing 20% dried whey, 17.5% dried skim milk, and 4%
      select menhaden fish meal (SMFM) or diets consisting of lactose and either 3.5
      and 7.0% SDAP or 4.0 and 8.0% LGPP added at the expense of dried skim milk on a
      digestible lysine basis. From d 0 to 7 after weaning, ADG and ADFI increased
      (linear, P < .05) with increasing SDAP. With increasing LGPP, ADG and ADFI
      increased and then decreased (quadratic, P < .10 and P < .05, respectively).
      Gain:feed ratio (G/F) was not affected by SDAP and was improved (linear, P < .05)
      for pigs fed increasing LGPP. In Exp. 4, 270 weanling pigs (initially 6.2 +/- 1.6
      kg and 20 +/- 3 d of age) were used to compare three diets that contained either
      2.5% spray-dried blood meal (SDBM), 4.8% SMFM, or 3.92% CPP; test feedstuffs were
      substituted on a total lysine basis and diets were fed from d 7 to 28 after
      weaning. Pigs fed CPP had decreased (P < .05) ADG and G/F compared with those fed
      the other protein sources. In Exp. 5, 255 weanling pigs (initially 5.3 +/- 1.2 kg
      and 17 +/- 2 d of age), were used to compare five diets that contained either
      2.5% SDBM, 5.51% SMFM, 4.17% CPP, 4.17% LGPP or 8.34% LGPP; feedstuffs were
      substituted on a digestible lysine basis and diets were fed from d 7 to 28 after
      weaning. No differences (P > .10) were observed in growth performance among pigs
      fed any of the protein sources within the experiment. However, pigs fed the LGPP
      had numerically greater ADG and better G/F than those fed CPP. In conclusion,
      these results suggest that LGPP can be an effective replacement for a portion of
      the SDAP in diets for weanling pigs.

PMID- 9928608
TI  - The effects of extrusion processing of carbohydrate sources on weanling pig
      performance.
AB  - Three experiments were conducted to study the effects of extrusion processing on
      growth performance of weanling pigs. In Exp. 1, 350 weanling pigs (initially 4.4
      +/- 1.0 kg BW and 10 +/- 2 d of age) were used to study the effects of various
      carbohydrate sources (corn, cornstarch, broken rice, wheat flour, and grain
      sorghum), with or without moist extrusion processing, on growth performance in a
      5 x 2 factorial arrangement of treatments. No carbohydrate source x extrusion
      processing interactions were observed (P > .10). Growth performance was not
      affected by extrusion processing; however, pigs fed corn had poorer growth
      performance (P < .05) than those fed other carbohydrate sources. In Exp. 2, 360
      weanling pigs (initially 5.0 +/- .5 kg BW and 10 +/- 2 d of age) were used to
      determine the interactive effects of ingredient processing and diet complexity on
      growth performance. Three processing combinations were used with either a simple
      or complex diet formulation in a 3 x 2 factorial arrangement of treatments. The
      three processing conditions were 1) pelleted only (control); 2) corn that was
      moist-extruded and then the complete diet was pelleted (extruded); or 3) the
      complete diet was expanded and then pelleted (expanded). Pigs fed extruded diets
      had a greater improvement in ADG as diet complexity increased than those fed
      other diets (processing x diet complexity interaction, P < .10). Pigs fed moist
      extruded corn had the best growth performance (P < .01). In Exp. 3, 210 weanling
      pigs (initially 6.8 +/- 1.5 kg BW and 21 +/- 2 d of age) were fed pelleted diets
      containing nonextruded corn (14.5% gelatinization; control) or corn extruded to
      provide 38.7, 52.7, 64.4, or 89.3% gelatinization. Average daily gain and ADFI
      decreased and then increased (P < .05), but apparent digestibility of DM, CP, and
      energy (P < .01) increased and then decreased with increasing gelatinization.
      These results indicate that moist extrusion processing of carbohydrate sources
      has variable effects on growth performance of early-weaned pigs and that the
      degree of gelatinization does not seem to be a major factor in explaining this
      variation.

PMID- 9928609
TI  - Total radioactive residues and clenbuterol residues in edible tissues, and the
      stereochemical composition of clenbuterol in livers of broilers after exposure to
      three levels of dietary [14C]clenbuterol HCl and three preslaughter withdrawal
      periods.
AB  - Thirty-six broiler chickens were randomly assigned to .5, 1.0, or 2.0 ppm dietary
      [14C]clenbuterol HCl for a 2-wk period starting at 5 wk of age. Four birds from
      each treatment were slaughtered after withdrawal periods of 0, 7, or 14 d. Total
      radioactive residues (TRR; clenbuterol HCl equivalents) were measured in adipose
      tissue, kidney, liver, skin with adhering adipose tissue, bile, blood, brain,
      gastrointestinal tract, heart, lung, spleen, and testes; parent clenbuterol was
      measured in liver and kidney. In edible tissues, TRR were roughly proportional to
      dietary [14C]clenbuterol level and inversely proportional to duration of the
      withdrawal period; kidney TRR ranged from nondetectable (14 d of withdrawal, .5
      and 1.0 ppm treatments) to 211.5 ppb for the 2.0 ppm treatment at zero
      withdrawal. Liver TRR were detectable for all treatment and withdrawal periods.
      Rapid depletion of TRR from edible tissues occurred during the first 7 d of the
      withdrawal period, but depletion of TRR was much slower thereafter. Parent
      clenbuterol was below the limit of detection (1 ppb) or was undetectable in liver
      and kidney for all dietary levels after 7 and 14 d of withdrawal, but it
      represented 22 to 48% of the total radioactive residues at 0 withdrawal. The
      inactive S (+) stereoisomer constituted approximately 73% of the total
      clenbuterol residue in livers of chickens slaughtered with no withdrawal period,
      and the active R (-) stereoisomer accounted for the remainder. These data
      indicate that radioactive residues of clenbuterol were present well after parent
      clenbuterol had depleted from edible tissues in chickens, and the predominant
      stereoisomer remaining in livers at slaughter was the inactive isomer.

PMID- 9928610
TI  - Estimation of energy expenditure from heart rate measurements in cattle
      maintained under different conditions.
AB  - We examined whether heart rate (HR) could be used to estimate energy expenditure
      (EE) in cattle. Six Hereford heifers (345 +/- 10.8 kg BW) 12 mo of age were
      implanted with HR radio transmitters and maintained in individual pens under the
      following treatments: 1) shade or sun exposure, 2) high- or low-energy diet, and
      3) feeding in morning or afternoon. The HR of animals was measured every .5 h
      during 3 mo; measurements of oxygen consumption and HR were made simultaneously
      in the morning and in the afternoon while animals were resting and exercising.
      Average daily HR (52 +/- 4 beats/min) and average daily EE (380 +/- 9 kJ/kg(.75))
      in animals on the low-energy diet were less than values in animals on the high
      energy diet (94 +/- 4 beats/min and 653 +/- 9 kJ/ kg(.75), respectively). For
      each animal and within each diet, linear regressions best described the
      relationship between HR and EE in resting animals, whereas quadratic regressions
      best described this relationship for exercising animals. The quadratic equation
      for the exercising animals could also be used for resting animals. In addition, a
      constant value of EE per heart beat (EE pulse) for each individual resting animal
      was found and gave accurate estimations. This method was convenient because 1) no
      exercise equipment was needed to generate the regression equations and 2) EE
      pulse was less affected by diet than was EE estimated by regression equations. We
      conclude that HR, a relatively easy measurement, can be useful and accurate in
      estimating EE. To increase the accuracy of the estimation of EE by HR, the
      relationship of HR to EE should be established for each animal. In addition, the
      nutritional regimen for the animal in which EE is estimated should be used for
      the animal in establishing the relationship.

PMID- 9928612
TI  - Production of bovine alpha-lactalbumin in the milk of transgenic pigs.
AB  - High production of milk and its components are necessary to allow maximal growth
      of developing pigs. In this study, transgenic pigs were produced containing the
      alpha-lactalbumin gene, whose product is a potential limiting component in the
      production of milk. Two lines of transgenic pigs were produced to analyze the
      effects that overproduction of the milk protein alpha-lactalbumin may have on
      milk production and piglet growth. Transgenic pigs were produced through
      microinjection of the bovine alpha-lactalbumin gene. The gene construct contained
      2.0 kb of 5' flanking region, the 2.0 kb coding region, and 329 bp of 3' flanking
      region. Sows hemizygous for the transgene produced as much as .9 g of bovine
      alpha-lactalbumin per liter of pig milk. The production of the bovine protein
      caused approximately a 50% increase in the total alpha-lactalbumin concentration
      of pig milk throughout a lactation. The concentration of bovine alpha-lactalbumin
      was highest on d 0 and 5 of lactation and decreased as lactation progressed. The
      ratio of bovine to porcine alpha-lactalbumin changed during the sow's lactation.
      This ratio was 4.3 to 1 on d 0 of lactation, but by d 20 of lactation the ratio
      was .43 to 1. This suggested that the bovine transgene and the endogenous porcine
      gene are under slightly different control mechanisms. The higher level of total
      alpha-lactalbumin present on d 0 of lactation was correlated with higher lactose
      percentage on d 0 in transgenic sows (3.8%), compared with controls (2.6%) (P <
      .01). Although there was also a trend for higher lactose percentage in transgenic
      sows on d 5 and 10 of lactation, no significant differences were observed. These
      data suggest that alpha-lactalbumin is limiting early in lactation of swine.
      Furthermore, higher concentrations of alpha-lactalbumin early in lactation may
      boost milk output.

PMID- 9928611
TI  - Sarcoplasmic reticulum responses to repeated sprints are affected by conditioning
      of horses.
AB  - Sarcoplasmic reticulum (SR) responses to repeated sprints and to physical
      conditioning were studied in 10 Quarter Horses. Exercise tests (four repeated
      sprints on a treadmill) were conducted before and after 12 wk of sprint
      conditioning. Muscle samples from the middle gluteal muscle were taken before and
      after each exercise test, and SR vesicles were isolated. Calcium uptake was
      determined spectrophotometrically using antipyrylazo III, and Ca2+-ATPase
      activity was determined using an enzyme-linked optical assay. Conditioning
      increased calcium uptake rate and Ca2+-ATPase activity by 14 and 38%,
      respectively, before exercise and by 25 and 26% after exercise. Exercise
      decreased calcium uptake rate and Ca2+-ATPase activity by 37 and 27%,
      respectively, before conditioning and by 28 and 21% after conditioning. Decreases
      in calcium uptake and Ca2+-ATPase activity of SR have been associated with
      fatigue during exercise, and this association is strengthened by the moderating
      effect of conditioning.

PMID- 9928613
TI  - In vitro maturation and fertilization techniques for assessment of semen quality
      and boar fertility.
AB  - The reliability of using different in vitro-derived measures of sperm quality to
      predict boar fertility was examined. On three occasions during a 20-wk period of
      breeding, special collections of the first sperm-rich fraction of the ejaculate
      from six boars were carried out. After in vitro capacitation procedures, three
      dilutions (5 x 10(5), 1.25 x 10(5), and 3.125 x 10(4) sperm/mL) of these semen
      samples were used in a standardized in vitro fertilization (IVF) test with
      oocytes recovered from prepubertal slaughterhouse ovaries and matured in vitro.
      Routine assessments of sperm motility, concentration, and morphology were also
      carried out for all collections used for AI during the 20-wk period. Semen from
      the same ejaculate, processed according to normal commercial practice using the
      AndroHEP extender, was used to inseminate equal numbers of recently weaned sows
      with either 3 x 10(9) or 2 x 10(9) total sperm, three times during the estrous
      period. Data from a total of 444 sows were used to determine boar fertility;
      between 12 and 54 sows were bred with each semen dose across the six boars. All
      measures of sperm fertilizing ability in vitro were different among boars (all P
      < .05) and use of different semen dilutions for IVF allowed further
      discrimination of apparent sperm quality among boars. The laboratory evaluation
      of semen collected during the period of breeding indicated effects of boar on
      ejaculate volume, total number of sperm per ejaculate, motility, and the
      percentage of sperm with normal morphology (all P < .01). Sperm dose used in AI
      had no effect on farrowing rate (80.7 vs 81.5%), but the lower AI dose resulted
      in a reduction (P < .05) in total numbers born (10.8 vs 10.0). For all three
      semen dilutions, estimated potential embryo production rate accounted for up to
      70% of the variation in litter size obtained with 3 x 10(9) sperm per AI dose,
      and the number of sperm attached per oocyte was a major factor accounting for
      variation in litter size obtained with 2 x 10(9) sperm per AI dose. These IVF
      variables may, therefore, be effective indicators of boar sperm quality for use
      in AI. With 2 x 10(9) sperm per AI dose, the percentage of sperm with normal
      morphology also explained a large part of the variance in litter size born (R2 =
      .59), indicating that morphological characteristics are a useful measure of semen
      quality.

PMID- 9928614
TI  - The effect of ram exposure on uterine involution and luteal function during the
      postpartum period of hair sheep ewes in the tropics.
AB  - St. Croix White hair sheep ewes lambing in July (n = 20) or November (n = 26)
      were used to evaluate the effect of ram exposure on uterine involution and
      postpartum luteal function. Ewes were exposed to an epididymectomized ram
      (EXPOSED) beginning on d 7 after lambing (d 0) or kept isolated from rams
      (CONTROL) through d 63. The width of each uterine horn was measured using
      transrectal ultrasonography at 3.5-d intervals beginning within 3 d after
      lambing. Jugular blood samples were also collected at these times, and plasma was
      harvested for progesterone (P4) analysis. Days to first estrus postpartum was not
      different (P > .10) between EXPOSED ewes that lambed in July or November (39.3 +/
      3.1 vs 44.2 +/- 3.8 d, respectively). Cross-sectional area of uterine horns was
      not different (P > .10) between EXPOSED and CONTROL ewes, ewes bearing one or two
      lambs, or ewes that lambed in November or July. Cross-sectional area of uterine
      horns in EXPOSED and CONTROL ewes had decreased to < 30% of initial values by 28
      d postpartum (P < .0001). Ewes exposed to rams had a P4 concentration greater
      than 1 ng/mL sooner postpartum (P < .006) than CONTROL ewes (32.4 +/- 2.4 vs 42.1
      +/- 2.3 d, respectively). The P4 concentration in the first sample greater than 1
      ng/mL was greater (P < .06) in EXPOSED ewes than in CONTROL ewes (3.3 +/- .4 vs
      2.3 +/- .4 ng/mL, respectively). In July, ewes exposed to rams had greater (P <
      .03) P4 concentrations than CONTROL ewes during the 63 d after parturition, but
      this difference was not apparent (P > .10) in ewes that lambed in November. Ram
      exposure did not hasten uterine involution in hair sheep ewes in the tropics.
      Luteal function, determined by plasma P4 concentrations, was enhanced by ram
      exposure during July but not during November. The lack of seasonality of hair
      sheep in the tropics does not seem to totally inhibit the response of ewes to ram
      exposure.

PMID- 9928615
TI  - The effect of in vitro fermentation on specific gravity and sedimentation
      measurements of forage particles.
AB  - Dry matter degradability (DMD), gas production (GP), functional specific gravity
      (FSG), volume of gas associated (GA), water-holding capacity (WHC), and
      sedimentation measurements of orchard-grass (OG) and alfalfa (AA) hays (ground
      through a 8-mm screen) were studied before and after in vitro incubation with
      ruminal fluid for 2, 4, 8, 24, 48, and 72 h. The DMD was higher for AA than for
      OG (P < .001), but GP did not differ. The FSG of unfermented OG and AA was .59
      and .73, respectively (P < .01). During fermentation, the FSG of OG increased
      more than did that of AA (from .93 to 1.39 for OG and from .97 to 1.27 for AA
      after 2 and 72 h, respectively), and GA decreased more rapidly (from .94 to -.04
      mL/g DM and from .74 to .15 mL/g DM, respectively). The DMD was positively
      correlated with FSG (r = .83; P < .001) and, therefore, negatively with GA (r = 
      .72; P < .01). The WHC increased similarly in the two forages with fermentation
      time. Unfermented and fermented samples were incubated in sedimentation columns
      filled with distilled water for 19, 37, 75, 150, and 300 s. After 300 s of
      sedimentation time, the unfermented AA and OG samples tended to float (91.1 and
      72.7% of DM, respectively). In contrast, fermented samples tended to sediment
      (90.7 and 90.9% of DM, respectively). There were only small effects of forage
      species and fermentation time on sedimentation tendency. Correlations between
      sedimentation measurements and DMD and FSG were not significant, with the only
      exception of DM recovered in the lower section of sedimentation columns after 75
      s, which was particularly correlated with DMD (P < .01) and FSG (P < .05). The
      results suggest that degradation rate of fibrous particles is related to changes
      in FSG and GA and, therefore, could influence ruminal transit. However, FSG was
      unable to predict accurately the sedimentation behavior of samples.

PMID- 9928616
TI  - Intestinal nutrient-gene interaction: the effect of feed deprivation and
      refeeding on cholecystokinin and proglucagon gene expression.
AB  - We tested the hypothesis that dietary components reaching the bovine small
      intestine influence the expression of genes that encode the gastrointestinal
      neuropeptides cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The
      amount of digesta reaching the intestine was manipulated during the experiment by
      withholding feed from five heifers fitted with ruminal, duodenal, and ileal
      cannulas for 48 h and then subsequent refeeding. Duodenal and ileal biopsies were
      collected using a fiber-optic endoscope. A Northern hybridization procedure was
      used to evaluate changes in gene expression. Blood concentrations of CCK and GLP
      1 were determined with RIA. The data indicate that CCK blood concentration and
      mRNA abundance decreased during the period of feed deprivation, but they returned
      to predeprivation values within 16 to 24 h of refeeding. The GLP-1 blood
      concentration also decreased during feed deprivation and returned to
      predeprivation values within 4 to 8 h of refeeding, despite the fact that
      proglucagon mRNA abundance did not change significantly during feed deprivation
      and refeeding. These findings provide evidence that CCK and GLP-1 are released in
      response to nutrients that reach the small intestine and may be involved in the
      physiological process of digestion and possibly play a role in regulating feed
      intake in ruminants.

PMID- 9928617
TI  - Manipulating ruminal fermentation: a microbial ecological perspective.
AB  - The essential role of ruminal microflora in ruminant nutrition provides the
      potential for improvement in animal production via altering the numbers or
      activities of specific classes of microorganisms. Successful alterations will be
      facilitated by an understanding of the microbial ecology of the rumen based on
      its mechanistic underpinnings. Demonstrated improvements in ruminal fermentation
      can be traced to their consonance with well-established principles of microbial
      ecology (niche occupancy, selective pressure, adaptation, and interactions) and
      the thermodynamics and kinetics of substrate utilization. Application of these
      principles to several proposed alterations of the ruminal bacterial population
      allows a prediction of their relative feasibility. Improving fiber digestion,
      decreasing protein degradation, and detoxifying feed components that are present
      in low concentrations will be difficult to achieve in the rumen and are best
      approached by altering the feed, either genetically or with postharvest
      treatment. By contrast, the detoxification of feed components present in high
      concentration, and redirection of electron disposal away from methanogenesis, are
      more productive targets for microbiological research.

PMID- 9928618
TI  - Manipulation of ruminal fermentation with organic acids: a review.
AB  - The dicarboxylic acids aspartate, fumarate, and malate stimulate lactate
      utilization by the predominant ruminal bacterium, Selenomonas ruminantium. Malate
      stimulates lactate uptake by S. ruminantium more than does aspartate or fumarate,
      and it seems that malate and sodium are involved in stimulating lactate
      utilization by this bacterium. Based on the ability of S. ruminantium to grow on
      malate in the presence of extracellular hydrogen and produce succinate, malate
      may be acting as an electron sink for hydrogen in the succinate-propionate
      pathway used by S. ruminantium. Incorporation of DL-malate into soluble starch
      and cracked corn fermentations with mixed ruminal microorganisms changed final
      pH, CH4, and VFA in a manner analogous to ionophore effects. When compared with
      either dicarboxylic acids or monensin alone, dicarboxylic acid plus monensin
      addition to cracked corn incubations stimulated the mixed ruminal microorganism
      fermentation to produce more propionate, less lactate, and increased final pH.
      Reduced lactate concentrations in dicarboxylic acid- and monensin-treated
      incubations most likely represents an additive effect of decreased lactate
      production by monensin-sensitive bacteria (i.e., Streptococcus bovis) and
      increased lactate utilization by the monensin-resistant S. ruminantium. The
      inclusion of malate as a feed additive into the diets of ruminants is currently
      not economically feasible; however, forages rich in organic acids might serve as
      vehicles for providing malate to ruminants. When five alfalfa varieties and three
      bermudagrass hay varieties were surveyed for malate content, the concentration of
      malate in both plant species declined as maturity increased. However, after 42 d
      of maturity, the concentration of malate in both forages ranged between 1.9 and
      4.5% of the DM. These results suggest that the incorporation of forage varieties
      that are high in malate may include malate economically into the diet and reduce
      losses associated with ruminal acidosis.

PMID- 9928619
TI  - Net flux of glucose, lactate, volatile fatty acids, and nitrogen metabolites
      across the portal-drained viscera and liver of pregnant ewes.
AB  - Our objective for this study was to determine the pattern of nutrient flux across
      the portal-drained viscera (PDV) and liver in ewes with varying numbers of
      fetuses. Catheters were placed in the hepatic portal vein, a branch of the
      hepatic vein, a mesenteric vein, and the abdominal aorta of ewes. Blood flow and
      net nutrient release across the PDV and liver were determined before exposure to
      rams. Ewes were then mated, which resulted in two ewes not pregnant and in six
      ewes with single and 11 ewes with twin lambs. Additional measurements were taken
      103, 82, 61, 39, 19, and 6 d before parturition. Net PDV glucose release did not
      differ from zero (-.4 +/- 8.4 mmol/h; P = .58). In ewes with singles, premating
      net hepatic glucose release was 34.4 +/- 2.4 mmol/h, and 19 d before parturition
      it was 46.2 +/- 3.8 mmol/h. In ewes with twins, premating net hepatic glucose
      release was 36.8 +/- 2.7 mmol/h, and 19 d before parturition it was 47.4 +/- 2.8
      mmol/h. Net PDV lactate release did not differ with litter size (P = .58) or days
      from parturition (P = .14; 9.7 +/- 4.6 mmol/h). Net lactate uptake by the liver
      increased in pregnant ewes as the pregnancy progressed (P < .001). The hepatic
      extraction ratio for lactate increased in late pregnancy (P = .02). Net PDV and
      hepatic release of acetate and propionate were not different with litter size or
      days from parturition. Hepatic extraction ratios of VFA did not differ with
      litter size or day from parturition. The patterns of change in hepatic metabolite
      fluxes are similar to the patterns of change in gravid uterus metabolite uptake.
      Hepatic lactate uptake seems to be regulated during pregnancy.

PMID- 9928620
TI  - Effect of dietary or abomasal supplementation of exogenous polysaccharide
      degrading enzymes on rumen fermentation and nutrient digestibility.
AB  - The effect of site of supplementation of a mixture of two crude preparations
      (Enzyme C and Enzyme X) of exogenous polysaccharide-degrading enzymes (EPDE) was
      studied in vivo using four ruminally and duodenally cannulated heifers (Exp. 1).
      The treatments were as follows: control (no EPDE), EPDE supplied through the diet
      (EF, 47.0 g/d), and EPDE infused continuously into the abomasum (EA, 41.6 g/d).
      Enzyme treatment increased the concentration of soluble reducing sugars (P < .05)
      and decreased NDF content (P < .05) in the treated feed, but this did not
      increase the rate or extent of in sacco disappearance of DM from the feed.
      Compared with control, ruminal fermentation was not affected by EF, but abomasal
      infusion increased (P < .05) rumen ammonia levels and shifted ruminal VFA
      patterns. Ruminal carboxymethylcellulase (CMCase) and xylanase activities were
      not affected by treatment. Abomasal infusion increased (P < .05) duodenal
      xylanase activity as compared with control and EF, but apparent digestion of DM,
      NDF, and CP were not affected by treatment. Negligible levels of CMCase and
      amylase reached the duodenum. During an in vitro experiment (Exp. 2), abomasal
      stability of the two EPDE was studied over a range of pH from 3.39 to .85, with
      or without pepsin. Carboxymethylcellulase activity (in Enzymes C and X) and beta
      glucanase activity (in Enzyme C) were largely unstable against pepsin proteolysis
      (P < .001) and low pH (P < .001). Xylanase and amylase activities were resistant
      to pepsin but irreversibly inactivated at low pH. These two experiments showed
      that abomasal supplementation of EPDE did not successfully supply cellulases and
      amylases to the intestine, due partially to their limited resistance to low pH
      and pepsin proteolysis. Although EPDE significantly increased the level of
      xylanase activity at the duodenum, this did not significantly improve total tract
      digestion.

PMID- 9928621
TI  - Amino acid and energy interrelationships in growing beef steers: II. Effects of
      energy intake and metabolizable lysine supply on growth.
AB  - We conducted three experiments to determine the optimal metabolizable Lys:net
      energy ratio for growth of beef calves. The single basal diet fed contained corn
      (56.1%), soybean hulls (18%), cottonseed hulls (15%), animal fat (4.25%), and
      corn gluten meal (5.6%). In Exp. 1, 54 steers were individually fed the basal
      diet at 1.5, 2.25, and 3.0 times NEm requirement; rations were top-dressed with
      3.4 g of rumen-stable (RS) Met and either 0, 2, 4, 6, 8, or 12 g of RS-Lys daily.
      An additional 18 steers were fed the same three levels of energy and supplemented
      with 125 g of blood meal per steer. In Exp. 2, 68 crossbred steers were subjected
      to the same experimental protocol, with the exception that only the two highest
      levels of energy were used. Of these steers, 48 were fed individually and
      received the RS-Lys treatments; the remaining 20 steers received 125 g of blood
      meal per steer. No interaction (P > .10) was detected between level of
      supplemental Lys and energy intake in Exp. 1 or 2. Supplementation with RS-Lys
      improved (P < .01) ADG in Exp. 1, but it had no effect (P > .10) on growth in
      Exp. 2. The Lys requirement estimates were 44.3 and 51.3 g/d, corresponding to
      maximal growth rates of 1.21 and 1.64 kg/d for the 2.25 and 3.0 times maintenance
      treatments, respectively. Comparing the growth rates of steers fed supplemental
      Lys with those of steers fed blood meal in Exp. 1 and 2 revealed an ADG advantage
      (P < .03) with blood meal supplementation. To confirm the blood meal response,
      Exp. 3 used 75 crossbred steers fed the basal diet at 3.0 times NEm requirement
      plus either 3.4 g RS-Met, 3.4 g RS-Met and 12 g RS-Lys, or 125 g of blood meal
      per steer. Blood meal supplementation improved (P < .01) growth of steers over
      those fed supplemental Met or Met plus Lys. Although a distinct relationship
      between amino acid requirements and energy supply may exist, Lys and Met were not
      first-limiting in these experiments, or selective supplementation with
      undegradable protein may have provided some factor that enhanced performance
      beyond that detected with Lys and Met alone.

PMID- 9928622
TI  - A comparison of learning styles and demographic characteristics of students
      enrolled in selected animal science courses.
AB  - Learning style is the method an individual uses to concentrate and to process and
      retain new information. This developmental set of characteristics can make
      identical instruction effective for some learners and ineffective for others.
      Even though learners are capable of mastering the identical information or
      skills, if they are taught through methods that complement their preferred
      learning style, analytical and global learners have different environmental and
      physiological needs. An important relationship between learning style and
      instruction is that individuals are likely to teach the way they prefer to learn.
      The objectives of this study were to identify learning styles of students
      enrolled in selected animal science courses. The majority (58%) of students
      enrolled in selected courses preferred a field-independent learning style
      (analytical). With respect to gender and learning style, there was no difference
      between males and females. Classification of high school demographics showed
      students from rural areas preferred a field-dependent learning style (global) and
      students from suburban or urban areas were more likely to prefer a field
      independent style. There was a difference in the preferred learning style of
      animal science faculty (field-dependent) and those students who declared their
      majors as animal science and preveterinary medicine (field-independent). The
      inverse relationship was found between dairy/poultry science faculty and
      students. Faculty should be aware of their own learning style and the learning
      styles of their students so they may facilitate learning for all students.

PMID- 9928623
TI  - Time course of enzyme induction in liver and kidneys and absorption, distribution
      and elimination of 1,4-dichlorobenzene in rats.
AB  - Time course of enzyme induction was measured in Fischer344 rats treated daily at
      150 and 600 mg 1,4-dichlorobenzene (1.4-DCB)/kg p.o. up to 28 days. The
      monoxygenases 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O
      deethylase (EROD) and aldrin epoxidase (ALD) as well as the phase II enzymes;
      epoxide hydrolase (EH), glutathione S-transferase (GS-T) and glucuronyl
      transferase (GLU-T) were dose-dependently induced in the liver of males and
      females. A pronounced induction in the kidneys was measured at 600 mg/kg only for
      ECOD. After single oral administration of 100 and 1000 mg/kg bw and feeding of
      100 and 1000 ppm (corresponding to approximately 10 and 100 mg/kg bw) to male
      Wistar rats for 28 days, the time course of 1,4-DCB and 2,5-DCP concentrations
      was investigated in plasma, adipose, hepatic and renal tissue. In addition, total
      urinary excretion of 2,5-DCP was determined. After single application, 1,4-DCB
      and 2,5-DCP were rapidly eliminated from the plasma and tissues, 40-60% of the
      dose administered was excreted as 2,5-DCP in the urine. There were no indications
      of cumulative effects after a feeding period of 28 days. The concentrations
      decreased in all tissues until the 7th day of study. Thereafter, there seems to
      be a steady state until the 28th day. A total of 7 days after the end of
      exposure, no more residues could be detected. Following long-term inhalation (450
      and 3000 mg/m3) 1,4-DCB concentrations were highest in adipose tissues at 6
      months followed by a marked decline at 18 months. 1,4-DCB and 2,5-DCP
      concentrations in plasma and liver were much lower but again with a peak at 6
      months. When compared with published human data on measurements in plasma, urine,
      liver and adipose tissue the results suggest that there should be no hazard for
      the general population.

PMID- 9928624
TI  - Prevention of carbon tetrachloride-induced hepatotoxicity in the rat by H.
      rosasinensis anthocyanin extract administered in ethanol.
AB  - The ability of anthocyanin obtained from the petals of H. rosasinensis to prevent
      carbon tetrachloride-induced acute liver damage in the rat was examined.
      Treatment of separate groups of rats with 2.5 ml of 1, 5 and 10% anthocyanin
      extract in 5% aqueous ethanol/kg body weight, 5 days/week for 4 weeks before 0.5
      ml/kg carbon tetrachloride (CCL4) resulted in significantly (P < 0.05) less
      hepatotoxicity than with CCL4 alone, as measured by serum aspartate and alanine
      aminotransferase activities 18 h after CCL4. These data suggest that H.
      rosasinensis anthocyanin may be protective against carbon tetrachloride-induced
      liver injury.

PMID- 9928625
TI  - Stimulation of the DNA binding activity of AP-1 by the peroxisome proliferator
      ciprofibrate and eicosanoids in cultured rat hepatocytes.
AB  - Peroxisome proliferators induce hepatic peroxisome proliferation and hepatic
      tumors in rodents. These chemicals increase the expression of the peroxisomal
      beta-oxidation pathway and the cytochrome P-450 4A family, which metabolize
      lipids, including eicosanoids. Peroxisome proliferators also induce increased
      cell proliferation in vivo. However, peroxisome proliferators are only weakly
      mitogenic and are not comitogenic with epidermal growth factor (EGF) in cultured
      hepatocytes. Our earlier studies found that the peroxisome proliferator
      ciprofibrate is comitogenic with eicosanoids. We therefore hypothesized that the
      comitogenicity of the peroxisome proliferator ciprofibrate and eicosanoids may
      result from a synergistic increase of the DNA binding activity of AP-1. Primary
      rat hepatocytes were cultured on collagen gels in serum-free L-15 medium with
      ciprofibrate, eicosanoids, and/or growth factors. The DNA binding activity of AP
      1 was determined in nuclear protein extracts by electrophoretic mobility shift
      assay. The DNA binding activity of AP-1 was not induced by ciprofibrate or
      eicosanoids alone, but the addition of eicosanoids along with ciprofibrate
      increased the induction of DNA binding activity of AP-1 at 30 min and 2 h after
      exposure. The combination of ciprofibrate and PGF2alpha blocked the inhibitory
      effect of transforming growth factor (TGF)-beta on the DNA binding activity of AP
      1 induced by EGF. These results show that the peroxisome proliferator
      ciprofibrate and eicosanoids co-stimulate the DNA binding activity of AP-1 and
      suggest that changes in eicosanoid concentrations may modulate mitogenic signal
      transduction pathways by the peroxisome proliferator ciprofibrate.

PMID- 9928626
TI  - Tissue distribution, subcellular localization and covalent binding of 2
      chloroaniline and 4-chloroaniline in Fischer 344 rats.
AB  - Chloroanilines (CA) are widely used chemical intermediates which induce numerous
      toxicities including hematotoxicity, splenotoxicity, hepatotoxicity and
      nephrotoxicity. Although chloroaniline-induced hematotoxicity has been studied in
      detail, little information is available on the organ-directed toxicity seen
      following exposure to these agents. The purpose of this study was to examine and
      compare the excretion and distribution of two nephrotoxicant and hepatotoxicant
      chloroanilines (2- and 4-chloroaniline) to liver, kidney, spleen, plasma and
      erythrocytes. Subcellular distribution and covalent binding in kidney and liver
      were also determined. Male Fischer 344 rats (four per group) were administered
      [14C]-2-chloroaniline or [14C]-4-chloroaniline (0.5 or 1.0 mmol/kg; approximately
      50 microCi/rat) intraperitoneally (i.p.). Urine, feces, blood and tissues were
      collected at 3 and 24 h. Both 2- and 4-chloroaniline-derived radioactivity were
      primarily renally excreted with < 1% excretion in the feces by 24 h post
      treatment. Both chloroanilines accumulated mainly in liver (percentage of
      administered dose/total tissue), but kidney generally had similar or higher
      equivalent concentrations (micromol/g tissue) compared to liver. Subcellular
      distribution revealed that for both chloroanilines, the cytosolic fraction
      generally had the highest level of radioactivity independent of time or dose.
      Covalent binding was detected in both liver and kidney, with the highest
      concentration (pmol/mg protein) of binding observed in the hepatic microsomal
      fraction regardless of compound, dose or time studied. In general, 2
      chloroaniline derived radioactivity was excreted faster, reached peak tissue
      concentrations earlier, disappeared from tissues faster and had less covalent
      binding in target tissue at 24 h than 4-chloroaniline-derived radioactivity.
      These results suggest that the increased toxic potential of 4-chloroaniline as
      compared to 2-chloroaniline may be due in part to a more prolonged and persistent
      accumulation of 4-chloroaniline and/or its metabolites in target tissue.

PMID- 9928627
TI  - Oxidative damage and fumonisin B1-induced toxicity in primary rat hepatocytes and
      rat liver in vivo.
AB  - Dietary fumonisin B1 (FB1) levels of 250 and 500 mg FB1/kg increased the level of
      thiobarbituric acid reactive substances (TBARS) significantly (P < 0.05) in the
      liver of rats fed FB1 over 21 days. Levels of 10, 50 and 100 mg FB1/kg also
      markedly (not significantly) increased the level of TBARS in the liver
      homogenate. Subcellular fractionation of the liver of the rats fed the 250 mg
      FB1/kg diet, showed a marginally significant increase of TBARS in the plasma
      membranes (0.05 < P < 0.1) and a significant increase in the microsomes (P <
      0.05). In vitro investigations in primary rat hepatocytes indicated that the
      level of TBARS was increased in a dose dependent manner associated with an
      increase in cytotoxicity. Addition of the antioxidant, alpha-tocopherol,
      significantly decreased the cytotoxicity whereas the level of TBARS was decreased
      to basal levels, suggesting that lipid peroxidation is likely to contribute to
      the cytotoxic effect of FB1. Addition of cumene hydroperoxide (CMHP) to primary
      hepatocytes exposed to FB1 for 44 h, enhanced the CMHP-induced TBARS release
      suggesting that the hepatocytes exposed to FB1 are more susceptible to chemically
      induced oxidative stress. Free radical production could result in excessive
      cellular damage and/or metabolic abnormalities that are likely to be involved in
      FB1-induced altered growth responses and cell death in primary hepatocytes. The
      hepatotoxic effects and resultant oxidative damage induced by FB1 may be
      important during cancer induction in rat liver by this apparently non-genotoxic
      compound.

PMID- 9928628
TI  - Sarcophytolide: a new neuroprotective compound from the soft coral Sarcophyton
      glaucum.
AB  - Bioactivity-guided fractionation of an alcohol extract of the soft coral
      Sarcophyton glaucum collected from the intertidal areas and the fringing coral
      reefs near Hurghada, Red Sea, Egypt resulted in the isolation of a new lactone
      cembrane diterpene, sarcophytolide. The structure of this compound was deduced
      from its spectroscopic data and by comparison of the spectral data with those of
      known closely related cembrane-type compounds. In antimicrobial assays, the
      isolated compound exhibited a good activity towards Staphylococcus aureus,
      Pseudomonas aeruginosa, and Saccharomyces cerevisiae. Sarcophytolide was found to
      display a strong cytoprotective effect against glutamate-induced neurotoxicity in
      primary cortical cells from rat embryos. Preincubation of the neurons with 1 or
      10 microg/ml of sarcophytolide resulted in a significant increase of the
      percentage of viable cells from 33 +/- 4% (treatment of the cells with glutamate
      only) to 44 +/- 4 and 92 +/- 6%, respectively. Administration of sarcophytolide
      during the post-incubation period following glutamate treatment did not prevent
      neuronal cell death. Pretreatment of the cells with sarcophytolide for 30 min
      significantly suppressed the glutamate-caused increase in the intracellular Ca2+
      level ([Ca2+]i). Evidence is presented that the neuroprotective effect of
      sarcophytolide against glutamate may be partially due to an increased expression
      of the proto-oncogene bcl-2. The coral secondary metabolite, sarcophytolide,
      might be of interest as a potential drug for treatment of neurodegenerative
      disorders.

PMID- 9928630
TI  - Flavonoid-induced alterations in cytochrome P450-dependent biotransformation of
      the organophosphorus insecticide parathion in the mouse.
AB  - The majority of insecticides currently in use throughout the world belong to the
      class of the organophosphorus insecticides. Many of these compounds, such as the
      phosphorothioate insecticides, exert their mammalian toxicity only after
      undergoing metabolic activation by a variety of cytochrome P450 isoforms to
      produce their corresponding oxygen analogs (or oxons), which are potent
      inhibitors of the critical enzyme acetylcholinesterase. Of the many chemicals
      identified that can modulate cytochrome P450-dependent activities, the flavonoids
      represent some of the most unusual compounds in that they have been reported to
      both inhibit and stimulate certain activities. The present study was undertaken
      to determine if representative flavonoids (at in vitro concentrations of 1-100
      microM) can alter the mammalian cytochrome P450-dependent biotransformation and
      acute toxicity of the phosphorothioate insecticide parathion. The flavonoids 5,6
      benzoflavone, flavone, and quercetin had the biphasic effect of stimulating mouse
      hepatic microsomal parathion oxidation at a concentration of 1 microM, and
      inhibiting this same activity when increased to 100 microM. In contrast, 7,8
      benzoflavone was only inhibitory at all concentrations examined. All the
      flavonoids examined except quercetin altered the ratio of
      activation/detoxification of parathion by mouse hepatic microsomes, but had no
      effect on this same ratio with human CYP1A2. These data suggest that the changes
      in the activation/detoxification ratio observed with mouse hepatic microsomes
      resulted from selective inhibition or stimulation of various cytochrome P450
      isoforms rather than a flavonoid-induced alteration in the nonenzymatic
      rearrangement of the putative phosphooxythirane intermediate generated by
      cytochromes P450 from parathion. Surprisingly, however, none of the four
      flavonoids in the current study affected the lethality of parathion in vivo,
      suggesting that the flavonoid-induced alterations in cytochrome P-450-dependent
      metabolism of parathion documented in vitro were simply not great enough to be of
      any significance in vivo.

PMID- 9928629
TI  - Increase of striatal dopamine release by cadmium in nursing rats and its
      prevention by dexamethasone-induced metallothionein.
AB  - Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg
      per day for 5 days) increased striatal dopamine (DA) release (180% of controls)
      and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased
      striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation
      (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase
      (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as
      a consequence of excessive dopamine release, since sulpiride (a specific D-2
      receptor antagonist) administration to Cd-treated rats abolished the effect of Cd
      on TH. No effect was observed on striatal monoamine oxidase (MAO) activity.
      Dexamethasone (Dx) treatment increased striatal MT content and caused no effect
      on either DA release or turnover. However, Dx administration prevented the
      effects caused by Cd, including the increased DA release and enhanced striatal
      lipid peroxidation. These results indicate that toxic effects on the brain are to
      be expected as a result of Cd exposure and that Dx administration can attenuate
      them.

PMID- 9928631
TI  - Low levels of inorganic lead noncompetitively inhibit mu-calpain.
AB  - Calpain is a ubiquitous calcium-dependent cysteine protease, whose cytoskeletal
      protein substrates suggest that it may be important in neuronal differentiation.
      Lead (Pb2+) is known to substitute for Ca2+ in a variety of intracellular
      processes, and interferes with the development of hippocampal neurons in vitro.
      We found that free Pb2+ at 1 nM does not activate calpain in the absence of Ca2+.
      Pb2+ inhibited the activity of calpain; the degree of calpain inhibition was
      dependent on an interaction between concentrations of both Ca2+ and Pb2+. In the
      presence of 1 microM free Ca2+, 10 pM free Pb2+ reduced calpain activity, but in
      the presence of 100 microM free Ca2+, 1 nM free Pb2+ failed to inhibit calpain.
      This provides evidence that Pb2+ competes for the Ca2+ binding sites on calpain.
      In the presence of 40 microM free Ca2+, 1 nM free Pb2+ significantly reduces Vmax
      without altering Km, suggesting that Pb2+ acts as a noncompetitive inhibitor of
      calpain. Inhibition of calpain is one mechanism by which Pb2+ may interfere with
      neuronal development.

PMID- 9928632
TI  - In vivo prevention of adriamycin cardiotoxicity by cyclosporin A or FK506.
AB  - The use of adriamycin, an antitumour agent, is restricted by its cardiotoxicity.
      The objective of this study was to investigate the role of mitochondrial Ca2+ in
      adriamycin-induced cardiotoxicity and the effect of either cyclosporin A (CsA) or
      tacrolimus (FK506) on that cardiotoxicity. A single dose of adriamycin (10 mg/kg
      body weight) caused myocardial damage that was manifested by elevation of serum
      enzymes, glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate
      transaminase (GPT), lactate dehydrogenase isoenzyme (LDH-iso) and creatine
      phosphokinase isoenzyme (CPK2-MB). The permeability of heart inner mitochondrial
      membrane of adriamycin-treated rats was examined. Tetraphenyl phosphonium ion
      (TPP+) uptake, estimated with a TPP+-sensitive electrode was used to monitor
      changes in heart inner mitochondrial membrane potential. Ca2+ efflux was measured
      spectrophotometrically with the Ca2+ indicator arsenazo III. The ability of heart
      mitochondria isolated from adriamycin treated rats to retain accumulated Ca2+ or
      TPP+ was sharply reduced. The increase of diagnostic serum enzymes and isoenzymes
      and the reduced ability to retain Ca2+ or TPP+ by heart mitochondria were
      restored to almost the normal levels when (500 microg/kg body weight) of CsA or
      FK506 were injected with adriamycin. The data suggested that adriamycin
      cardiotoxicity might be due to the increase of inner membrane permeability in
      heart mitochondria as a result of increasing the sensitivity of a Ca2+ dependent
      pore of the inner mitochondrial membrane to calcium, leading to dissipation of
      membrane potential and release of pre-accumulated Ca2+. Suitable antagonists of
      Ca2+-dependent pore formation such as CsA or FK506 may improve heart tolerance to
      adriamycin.

PMID- 9928633
TI  - Bidirectional transport of cadmium across apical membrane of renal epithelial
      cell lines via H+-antiporter and inorganic anion exchanger.
AB  - The purpose of this study was to investigate whether cadmium (Cd) efflux across
      the apical membrane of renal epithelial cells is mediated via a H+-antiport
      system, and to confirm the re-uptake of Cd from the apical membrane via an
      inorganic anion exchanger. LLC-PK1 and OK cell monolayers cultured on permeable
      membranes were incubated with 1 microM CdCl2 added to the basolateral medium, and
      the transport of Cd from the basolateral to apical medium and the accumulation of
      Cd in the monolayers were measured. Cd transport was increased by lowering the pH
      of the apical medium and was accompanied by a decrease in Cd accumulation.
      Coincubation with N'-methylnicotinamide or cisplatin, which act as substrates of
      the H+-antiport systems, decreased Cd transport and increased Cd accumulation in
      a concentration-dependent manner. To confirm the re-uptake of Cd, LLC-PK1 cell
      monolayers were pretreated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
      (DIDS), a specific inhibitor of an inorganic anion exchanger, before incubation
      with CdCl2. Pretreatment with DIDS significantly increased Cd transport and
      decreased Cd accumulation at an apical medium pH of 7.4, but not at pH 5.5. These
      results suggest bidirectional transport of Cd across the apical membrane of renal
      epithelial cells via a H+-antiport system (efflux) and an inorganic anion
      exchanger (influx), depending on the pH of the apical side.

PMID- 9928634
TI  - Apical uptake of radiolabelled ochratoxin A into Madin-Darby canine kidney cells.
AB  - Uptake of ochratoxin A (OTA) across the apical cell membrane of collecting duct
      cells is the first step in reabsorption and partly mediated by proton-dipeptide
      cotransport. As the remaining part of apical OTA uptake remained unclear, we
      studied the characteristics of apical uptake of tritium-labelled OTA (3H-OTA) in
      MDCK-C11 cells in detail. Uptake of 3H-OTA was pH- and temperature-dependent and
      led to intracellular accumulation of OTA. Lowering pH led to an increase and
      lowering temperature (4 degrees C) to a decrease of OTA uptake. Besides
      dipeptides, the beta-lactam antibiotics cephalexin and ceftibuten inhibited the
      3H-OTA uptake also confirming the role of the proton dipeptide cotransporter. In
      addition, substrates of organic anion transporter, taurocholate and methotrexate,
      inhibited 3H-OTA uptake in part. Aspartylphenylalanine methyl ester (aspartame)
      had no inhibitory effect on 3H-OTA uptake. Uptake of OTA was not dependent on
      sodium. Sixty minutes of preincubation with phorbol 12-myristate 13-acetate (PMA)
      led to increased apical uptake of OTA. The PMA effects were inhibited by
      ethylisopropylamilorid (EIPA). We conclude that apical uptake of OTA occurs by
      Na+-independent transport. One part of the uptake is mediated by proton-dipeptide
      cotransport (30%, dipeptide-inhibitable), by organic anion transporter (20%,
      taurocholate-inhibitable) and by diffusion (20%, responsible for uptake at 4
      degrees C). The remaining part occurs by as yet unidentified but pH-dependent
      transport mechanisms. An acidic urine in distal parts of the nephron provides
      thus the main risk for OTA uptake leading to its reabsorption and consequently
      alkalinisation of the urine should help to prevent this reabsorption.

PMID- 9928635
TI  - A systematic review of clinical research addressing the prevalence, aetiology,
      diagnosis, prognosis and therapy of otitis media in Australian Aboriginal
      children.
AB  - The objective of this review was to systemically identify and summarize all the
      clinically relevant evidence available from studies addressing the prevalence,
      aetiology, diagnosis, prognosis and therapy of otitis media in Australian
      Aboriginal children. Electronic searching of Medline, the Australian Medical
      Index and the Aboriginal and Torres Strait Islander Health Bibliographic Index
      was performed. This was supplemented by hand searching the Menzies School of
      Health Research otitis media collection, the Aboriginal and Torres Strait
      Islander Health Information Bulletin and Aboriginal Health: an annotated
      bibliography. Data were extracted and placed in a series of evidence tables
      relevant to clinical practice. There were 59 studies that met the inclusion
      criteria. The majority were surveys, and only 19 addressed diagnosis, prognosis
      or therapy. Severe otitis media in rural Aboriginal children does not occur in
      isolation but as part of a spectrum of chronic bacterial infections of the
      respiratory tract. Although the aspects of poverty that result in this condition
      remain to be clarified, exposure to other young children with chronic nasal
      discharge is likely to be important. Whilst there is a considerable amount of
      literature on otitis media in Australian Aboriginal children, the number of
      studies most relevant to improving health outcomes is small. A systematic
      approach to disease surveillance, diagnosis, and application of medical
      interventions is required urgently. Future medical research should be concerned
      with the evaluation of interventions and the generalisabilty of studies from
      different populations.

PMID- 9928636
TI  - Antibiotics for sore throats?
AB  - Although not explicit, recommendations in the new edition of Therapeutic
      Guidelines: Antibiotic have taken a lurch towards an evidence basis. What does
      this mean, and what is the basis of the recommendation that antibiotics be used
      for sore throat in very limited circumstances?

PMID- 9928637
TI  - Cardiopulmonary resuscitation.

PMID- 9928638
TI  - Clonidine: adverse responses.

PMID- 9928639
TI  - Cardiopulmonary resuscitation in the newborn intensive care unit.
AB  - OBJECTIVES: To determine the outcome for cardiopulmonary resuscitation (CPR)
      following cardiac arrest, and the predictors of response to CPR, in newborn
      infants with a diverse range of medical, surgical and cardiological problems
      cared for in a tertiary level newborn intensive care unit (NICU). METHODOLOGY:
      Infants who had suffered a cardiac arrest and received CPR were identified by
      retrospective review of the NICU medical records. RESULTS: Thirty-five (1%) of
      3624 infants admitted to the NICU during a six-year period received CPR because
      of a cardiac arrest. Twenty (57%) of the infants did not respond to CPR and died
      within 2.5 h (non-responders), eight (23%) responded to CPR but died before
      discharge from hospital (short-term responders), and seven (20%) responded to CPR
      and were discharged from hospital (long-term responders). The arterial pH was
      significantly lower in non-responders to CPR compared with responders. Non
      responders to CPR were not significantly different from responders with regard to
      gestational age, birth weight, age at arrest, systolic blood pressure, blood
      gases, severity of respiratory failure, or renal function. In 24 infants (68%),
      the precipitating cause for the cardiac arrest was either irreversible (20), or
      not known (4) and all died prior to discharge from hospital. In 11 infants (32%),
      the cardiac arrest was considered to have been precipitated by an acute and
      reversible event, and seven (64%) survived to discharge from hospital. All six
      infants with septicaemic shock were non-responders to CPR. Three of 15 infants
      with complex congenital heart disease were long-term responders to CPR but none
      survived without a major physical and psychomotor disability. CONCLUSION: The
      present study offers support for the recommendation that CPR may be withheld in
      infants who do not have a reversible cause for their cardiac arrest but are dying
      or will die soon from the inexorable progress of their illness.

PMID- 9928640
TI  - Clonidine overdose in childhood: implications of increased prescribing.
AB  - OBJECTIVE: To highlight the increase in the number of cases of clonidine overdose
      admitted to a specialist paediatric hospital, with particular reference to the
      clinical features, clinical course and circumstances surrounding the incident.
      METHODS: Cases of clonidine overdose were identified by review of the emergency
      department attendance register, the intensive care unit database and inpatient
      statistics collection. Case notes were reviewed to determine the clinical
      features, history and clinical course in each case. RESULTS: Fifteen patients
      experienced 16 overdoses during the period 1990-97 inclusive. Only one case
      occurred before 1994. Depressed level of consciousness and bradycardia were the
      most common clinical manifestations, and were observed in 75 and 88% of cases
      respectively. There were no fatalities. Five patients received naloxone. Other
      treatment modalities included gastrointestinal decontamination, atropine,
      ventilation and inotropic support. Fourteen cases occurred in association with
      medication prescribed for attention-deficit hyperactivity disorder (ADHD).
      CONCLUSION: Clonidine overdose is a potentially serious condition, often
      requiring intensive care management. Our experience suggests that it is a growing
      problem, related in part to its increased use in the treatment of ADHD.
      Preventive strategies, including raising the level of awareness of risks, changes
      to packaging and appropriate selection of patients for treatment, need
      consideration if further overdoses are to be prevented.

PMID- 9928641
TI  - Filling the gap: weaning practices of children aged 0-2 years in western
      metropolitan Melbourne.
AB  - OBJECTIVE: To investigate weaning practices of children aged 0-2 years in
      Melbourne's western metropolitan region (WMR). METHODOLOGY: The study group
      comprised children aged 0-2 years attending six maternal and child health centres
      in the City of Brimbank in Melbourne's WMR. One hundred and nineteen parents were
      asked to complete a questionnaire about their child. Interpreters were used as
      required. In total, 115 questionnaires were completed representing a response
      rate of 97%. All maternal and child health nurses working in the target region
      were asked to complete a questionnaire. Of these, five were selected randomly to
      participate in follow-up indepth interviews. Weaning was defined as the addition
      of food/fluids other than breast milk or formula. RESULTS: The mean age for the
      introduction of solids was 4.3 months. Of the children already introduced to
      solids, 67% had commenced between 4 and 6 months whilst 29% of the infants were
      taking solids by 3 months of age. Of the children already having juice, 85% had
      done so by the age of 6 months. The mean age for the introduction of cow's milk
      as the main drink was 10.7 months (S.D. 2.8). For English speaking families the
      mean age was 11.3 months (S.D. 1.8) whilst for families speaking languages other
      than English the mean age was 9.7 months (S.D. 4.1). CONCLUSIONS: Most parents in
      this group were following the recommended guidelines for weaning. Some parents
      had poor knowledge of appropriate weaning time, use of fruit juice and
      introduction of cow's milk as the main drink. Additional information and
      education is required in these areas. Further investigation is required in
      relation to use of cow's milk and ethnicity.

PMID- 9928642
TI  - Arthrogryposis multiplex congenita in Western Australia.
AB  - OBJECTIVE: Determination of the prevalence of arthrogryposis multiplex congenita
      in Western Australia as well as the causes of the condition. Overseas reports
      varied considerably and no such survey had been conducted in Western Australia.
      METHODOLOGY: Case names were obtained from various registers and records as well
      as from private practitioners covering the 14 years birth cohort between 1980 and
      1993. The records, and where possible the patients, were seen by one of the
      authors. Diagnosis was further established through relevant investigation where
      possible. RESULTS: Thirty cases were identified, giving a birth prevalence of
      approximately 1 in 12000. In nine cases there were significant abnormalities of
      the central nervous system, in seven cases anterior horn cell and/or peripheral
      nervous involvement was the cause and in three there was primary muscle disease.
      The remaining 11 had various syndromes for which no definite neuropathological
      lesions could be demonstrated, but most of these had syndromes such as distal
      arthrogryposis or amyoplasia. Mortality was 37%. Talipes occurred in 23 of 30
      cases. Early intervention and, in more severe cases, radical surgical
      intervention was the management adopted in most cases. CONCLUSION: The birth
      prevalence of arthrogryposis in Western Australia is somewhat less than that
      reported in Canada and Finland but somewhat greater than the Edinburgh figures,
      which appear to be the extremes quoted in the literature. Prognosis is worse in
      cases with serious central nervous system involvement and/or chest involvement,
      and better in cases of localised arthrogryposis (e.g. distal), as well as in the
      specific syndrome of amyoplasia as described by Hall.

PMID- 9928643
TI  - Paediatric resuscitation--by phone.
AB  - OBJECTIVE: To ascertain the training and knowledge of paediatric resuscitation
      amongst all paediatric residents in New Zealand. METHOD: A validated national
      telephone survey. RESULTS: Interviews were conducted with 96 out of a possible
      109 paediatric residents. Most had been qualified less than 5 years and a third
      had received some training in paediatric resuscitation in the last year. The
      initial dose of intravenous adrenaline was known by 61% but only 10% knew the
      recommended ten-fold increase in subsequent doses. Recognition of the importance
      of cervical spine management in trauma was poor. Correct resuscitation fluids and
      volumes were selected by 90%, though infusion rates were frequently too slow.
      Residents with paediatric qualifications and greater experience scored
      significantly higher. CONCLUSION: Many junior paediatric staff are inadequately
      prepared for resuscitating children. We believe improved regular training is
      required and that the introduction of a nation-wide Advanced Paediatric Life
      Support course, subsequent to the completion of this survey, will lead to
      improved standards. Its effectiveness needs to be audited.

PMID- 9928644
TI  - An investigation into sleep characteristics of children with autism and
      Asperger's Disorder.
AB  - OBJECTIVE: The aim of the study was to investigate the specificity of sleep
      problems in children with autism and further explore the currently unclear
      association between sleep problems and daytime behaviour. METHODOLOGY: The
      Pervasive Developmental Disorder (PDD) group consisted of 31 children with autism
      and 7 children with Asperger's Disorder ranging in age from 44 to 152 months. The
      control group consisted of 36 children ranging in age from 63 to 171 months. The
      children were matched on age and gender, and group-matched on IQ level. A sleep
      diary was completed by parents over a 2-week period, in addition to several
      behaviour questionnaires. RESULTS: Results showed that children in the PDD group
      exhibited qualitatively and quantitatively different sleep patterns to
      nonautistic control children. CONCLUSIONS: The findings were discussed in light
      of current literature concerning circadian rhythm dysfunction, social
      difficulties, and abnormal melatonin levels in children with autism.

PMID- 9928645
TI  - Predicting readmission to hospital with asthma.
AB  - OBJECTIVES: To determine whether readmission to hospital for children aged 1-7
      years with asthma can be predicted; and to discover whether factors related to
      the severity of the attack and past pattern of asthma, assessment of the parents'
      intention to treat the child with inhaled therapy, perceived consequences of
      treatment, habits of treatment and self-efficacy show a difference between those
      children subsequently readmitted and those who were not. METHODS: A specifically
      developed questionnaire was administered to parents of 121 children admitted with
      asthma. Clinical assessment was made of severity of the acute attack and past
      pattern of the asthma. One year after admission subjects were reviewed to
      determine those who had been readmitted. RESULTS: On univariate analysis, the
      negative perceived consequences of treatment with inhaled therapy were associated
      with an increased risk of readmission over a one-year period (P = 0.04). After
      adjusting for confounders (place of birth of mother, two- or one-parent family)
      and the effect-modifier of past pattern of the asthma (infrequent episodic,
      frequent episodic, persistent), the greater the negative perceived consequences
      of treatment, the more likely there would be readmission in children with
      infrequent episodic asthma. After adjusting for potential confounders, using
      logistic regression a decrease of one standard deviation in the negative
      perceived consequences score resulted in a one-third decrease in the odds of
      readmission (odds ratio (OR) = 0.31, 95% CI 0.12-0.83). CONCLUSIONS: Parents
      whose children are readmitted see greater negative perceived consequences of
      treatment. If asthma is infrequent episodic, the negative perceived consequences
      may be an inhibitor of treatment, whereas for more severe past patterns of asthma
      the severity is the controller of treatment. If parental negative consequences
      could be decreased, admissions for asthma may decrease.

PMID- 9928646
TI  - Post-traumatic stress disorder in paediatric patients and their parents: an
      exploratory study.
AB  - OBJECTIVE: To determine the prevalence of post-traumatic stress disorders (PTSD)
      in a selected population of paediatric patients and their parents. METHODOLOGY:
      Twenty-three high-risk patients (serious accidents, newly diagnosed cancer) and
      11 low-risk patients (simple planned surgery) and their parents were
      consecutively selected and assessed 6-8 weeks after the event with a DSM-IV based
      diagnostic interview and the PTSD Symptom Scale. RESULTS: There is a high
      prevalence of PTSD in children and parents of the high-risk group. In the low
      risk group such disorders are almost nonexistent. Parents in both groups report
      more PTSD symptoms than their children. Sex and age of the child and duration of
      hospitalisation have no significant influence on the development of PTSD.
      CONCLUSIONS: The high prevalence of PTSD in high-risk paediatric patients and
      their parents offers support for the applicability of a post-traumatic stress
      model for understanding the psychological impact of accidents, severe illnesses
      and their medical treatment.

PMID- 9928647
TI  - Interobserver reliability of the click test: a rapid bedside test to determine
      surfactant function.
AB  - OBJECTIVE: To determine the interobserver reliability of the click test, a rapid
      bedside test of surfactant function. METHODOLOGY: One hundred samples (48
      amniotic fluid, 28 gastric aspirates, 24 tracheal aspirates) were obtained from
      pregnant women, term and preterm infants managed at two perinatal centres.
      Gestational ages of the pregnancies or infants at time of sampling ranged from 24
      to 40 weeks (mean +/- s.d.: 31+/-5). The click test was performed independently
      by two observers, with differing levels of experience, and blinded to each
      other's results. Interobserver reliability was determined for samples classified
      as negative (no clicking bubbles), equivocal (a few clicking bubbles seen after 2
      min of looking), and positive (clicking bubbles seen easily on first look). As
      negative and equivocal test results suggest surfactant dysfunction, these results
      were also combined to provide a dichotomised result. RESULTS: For samples
      classified as negative, equivocal and positive the interobserver agreement was
      0.83, with agreement beyond chance shown by a quadratic weighted Kappa of 0.74
      (95% CI = 0.62-0.86). When negative and equivocal results were combined, the
      simple Kappa was 0.73 (95% CI = 0.59-0.87). CONCLUSIONS: The click test has a
      high level of interobserver reliability. It is rapid, simple, accurate and able
      to be taught to medical and nursing staff with appropriate training. It has many
      potential applications including the prediction of fetal lung maturity in women
      with premature rupture of membranes, and in term and preterm infants who require
      the bedside testing of surfactant function.

PMID- 9928648
TI  - Randomised trial of histoacryl blue tissue adhesive glue versus suturing in the
      repair of paediatric lacerations.
AB  - OBJECTIVE: To compare histoacryl blue tissue adhesive glue with suturing in the
      repair of simple paediatric lacerations. METHODOLOGY: Prospective, randomised
      controlled trial in tertiary paediatric emergency department. Children 4 years
      old or older with non-ragged lacerations <5 cm in length, <12-h-old and not
      involving eyelid or mucous membrane. A total of 163 patients were randomly
      allocated to either glue (83 cases) or sutures (80 controls) to repair their
      laceration. Primary outcome measures were cosmetic outcome at 3 and 12 months
      with secondary outcomes-length of time to perform procedure, and pain assessment
      of procedure by doctor, nurse, parent and child. RESULTS: Cases and controls were
      similar in age, wound length and width and body part involved, but more females
      received glue (P = 0.013). Time taken to repair the wound was faster in the glue
      group (median 0-2 mins vs. 6-10 min suture, P<0.001). Doctors (P = 0.02), nurses
      (P<0.01) and parents (P = 0.02) but not the children themselves (P = 0.24) rated
      glue repair as less distressing. Complications at 1 week (wound dehiscence,
      redness and discharge) were the same for both groups (P>0.2). Cosmetic outcome
      was the same for both groups at 3 (n = 65) and 12 (n = 65) months (P>0.7).
      CONCLUSION: Tissue adhesive glue is faster and probably less painful than
      suturing. Tissue adhesive glue has the same cosmetic result as suturing when used
      for the repair of simple lacerations in children.

PMID- 9928649
TI  - Mortality and neurodevelopmental outcome for infants receiving adrenaline in
      neonatal resuscitation.
AB  - OBJECTIVE: To document the outcome, in terms of mortality and morbidity, for all
      infants requiring adrenaline as part of initial neonatal resuscitation, and to
      identify the differences between term and preterm infants. METHODS: All infants
      in a five-year period who received adrenaline during delivery room resuscitation
      were retrospectively identified. Data from the perinatal period were ascertained
      by chart review. Details of survivors at 1 year or later were reviewed. RESULTS:
      Seventy-eight infants were identified representing 0.2% of all deliveries. Over
      half of all infants survived, with the proportion increasing with advancing
      gestational age from 30% below 29 weeks to 67% at term. Seventy-three per cent of
      survivors were normal at follow-up to at least 1 year, with more preterm infants
      being normal than term infants (79% vs. 64%). Over half of survivors below 29
      weeks' gestation were normal, but overall 78% of this group either died or showed
      evidence of neurodevelopmental disability. Asystolic infants did not differ from
      the bradycardic infants in terms of survival or rates of disability. Adrenaline
      may be contraindicated in asystolic very preterm infants. CONCLUSIONS: Adrenaline
      retains a role in term and mature preterm infants where there is an acute cause
      for depression at delivery. In very preterm infants its use is associated with a
      high rate of death and disability. Failure to stabilise with adequate ventilatory
      support should be seen as a poor prognostic sign in this group.

PMID- 9928650
TI  - Sun protection behaviours and the predictors of sunburn in young children.
AB  - OBJECTIVE: To explore the use of sun protection behaviours and the experience of
      sunburn in a sample of parents and their children in New Zealand. METHODOLOGY:
      Information was collected from 887 parents using postal questionnaires at the
      beginning of and during the summer. RESULTS: Thirty per cent of the parents
      believed their child looked healthier with a suntan, and 40% intended to let
      their child get a suntan during the summer. Predictors of intention to tan
      included level of parental education, the child's age, the child's sensitivity to
      burning and experience of sunburn in the parent. At the end of the summer period,
      29% of the children were reported as being sunburned. Predictors of sunburn in
      the child were the age of the child, experience of sunburn in the parent and use
      of sunscreen SPF15+ by the parent. CONCLUSION: Despite intense media coverage of
      the dangers of overexposure to the sun, it is clear that a significant proportion
      of children are still getting sunburned.

PMID- 9928651
TI  - Low dose oral anticoagulation therapy in Chinese children with congenital heart
      disease.
AB  - OBJECTIVES: This study aims to evaluate the efficacy of a low dose warfarin
      regimen for Chinese children requiring anticoagulation therapy and its safety
      when monitored on an outpatient basis. Current recommendations are based on
      extrapolations from the adult experience and a high target international
      normalised ratio (INR) is adopted amongst the Western countries. METHODOLOGY:
      This is a 10-year retrospective study from January 1986 to June 1996.
      Effectiveness of warfarin therapy was monitored by the prothrombin time,
      standardised and expressed as the INR. A target INR of 1.5-2.5 was adopted for
      children with cardiac diseases requiring anticoagulation therapy for primary and
      secondary prophylaxis against thromboembolism. From the clinical records,
      demographic data, induction warfarin dosage, changes of dosages and related
      events on follow-up, frequency of outpatient visits, complications and serial INR
      results were reviewed. RESULTS: Thirty-five patients (23 boys, 12 girls) were
      included with a mean age at initiation of warfarin therapy of 8.4+/-5.8 years.
      Amongst these, 66% (n = 23) were after isolated valvar replacement, 28% (n = 10)
      after Fontan operation with or without valvar replacement and 6% (n = 2) after
      deep vein thrombosis. Regression estimate of the induction dose was 0.05-0.13 mg
      x kg(-1) in order to achieve the target INR range after 2 days of warfarin
      therapy. The daily maintenance warfarin dose was correlated with the bodyweight
      [dose (mg x day(-1))= 0.04 x bodyweight (kg) + 0.87, r = 0.63, P<0.0001]. Young
      children required significantly higher daily warfarin maintenance dose when
      adjusted for bodyweight [dose (mg x kg day(-1)) = antilog(10)?-0.02 x age (years)
      0.80?, r = -0.74, P<0.0001]. The mean maintenance warfarin dosage was
      significantly lower in patients after the Fontan operation, with or without
      valvar replacement, in the absence of apparent liver dysfunction. The total
      period of followup was 159 patient-years. No serious bleeding complications or
      embolic phenomena were documented. One patient died of thrombosis of the mitral
      valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient
      years. CONCLUSIONS: A low dose warfarin regimen to maintain a target INR of 1.5
      2.5 provides adequate protection in Chinese children against thromboembolism
      whilst allowing safe outpatient monitoring of the anticoagulation status.

PMID- 9928652
TI  - Cyclic vomiting syndrome in South-East Asian children.
AB  - OBJECTIVE: To describe the clinical features, management and outcome of children
      with cyclic vomiting syndrome (CVS) from South-East Asia. METHODOLOGY:
      Retrospective review of all children who fulfilled the diagnostic criteria of CVS
      and who were seen at Department of Paediatrics, University of Malaya Medical
      Centre, Kuala Lumpur and Paediatric Unit, Penang Hospital, Penang, Malaysia from
      1987 to 1997. RESULTS: Eight children with CVS were seen at the two units during
      the study period, five girls and three boys. All had cyclical, self-limited
      episodes of nausea and vomiting with symptom-free intervals. The mean age of
      onset was 5.9 years. The clinical features were similar to other series described
      in the literature. Only two of the eight children were described as
      'perfectionist'. Two children identified stress as precipitating factors. Therapy
      to reduce the number of emeses during acute attacks and to prevent subsequent
      attacks had been ineffective. CONCLUSION: There are similarities and differences
      in CVS from South-East Asian children as compared to those described in the
      literature.

PMID- 9928653
TI  - An aetiological profile of short stature in the Indian subcontinent.
AB  - OBJECTIVE: To determine the aetiological causes of short stature in a developing
      region of the world. METHODOLOGY: A retrospective analysis was made of data from
      193 subjects who were primarily evaluated for short stature in the Endocrinology
      Department, Institute of Medical Sciences, Kashmir, India. These subjects had a
      height of more than 3 standard deviations (SD) below the mean for their age and
      sex, and were seen over a decade (January 1987 to December 1996). A logical and
      comprehensive clinical and investigative protocol was followed to identify the
      aetiology of short stature. RESULTS: Growth hormone deficiency was the commonest
      identifiable cause of short stature and accounted for 22.8% of cases. Thirty-six
      subjects (18.7%) had a normal variant short stature. Renal tubular acidosis was
      diagnosed in 10.4%, primary hypothyroidism, malnutrition and hypothalamic
      syndrome in 7.8% each, and growth hormone insensitivity syndrome in 4.1% cases.
      CONCLUSIONS: We conclude that, in addition to growth hormone deficiency and
      normal variant short stature, distal renal tubular acidosis and growth hormone
      insensitivity syndrome are significant causes of short stature in India.

PMID- 9928654
TI  - Gentamicin dosage intervals in neonates: longer dosage interval--less toxicity.
AB  - OBJECTIVES: The aim of this study was to determine the incidence of toxic trough
      serum gentamicin levels in neonates in the first week of life, with different
      dosage intervals. METHODS: This was a retrospective study of neonates born
      between 01.07.95 and 31.12.95, who received gentamicin. Data were collected on
      birth weight, gestation, gentamicin dose, the trough level of gentamicin, serum
      creatinine and urine output. A trough serum gentamicin level of > or =1.5 mg/L
      was considered toxic. RESULTS: One hundred and seventy infants met the study
      criteria. All 21 infants in group one (24-29 weeks) received gentamicin with a
      dosage interval of 24 h. Sixteen (76%) infants had toxic trough serum gentamicin
      levels. In group two (30-34 weeks) 8 infants had gentamicin q12hly and all (100%)
      had toxic trough serum gentamicin levels. Fourteen infants had gentamicin every
      18 h and 13 (93%) had toxic trough serum gentamicin levels. Sixty-one infants had
      gentamicin q24hly and 25 (41%) had toxic trough serum gentamicin levels. The
      differences in proportions with toxic levels were statistically significant. In
      group three (> or =35 weeks) 29 infants had gentamicin q12hly and 25 (86%) had
      toxic trough serum gentamicin levels. Six infants had gentamicin every 18 h and 2
      (33%) had toxic trough serum gentamicin levels. Thirty-one infants had gentamicin
      q24hly and 4 (13%) had toxic trough serum gentamicin levels. The differences in
      proportions comparing infants having gentamicin q12hly with those having it
      q24hly were statistically significant. CONCLUSIONS: A starting gentamicin dosage
      interval of 12 h in infants of any gestational age, or a starting dosage interval
      of 24 h for infants of less than 30 weeks gestational age, leads to most having
      toxic trough serum gentamicin levels. In infants of 30 weeks gestational age or
      greater, most have safe non-toxic trough serum gentamicin levels if started on a
      dosage interval of 24 h.

PMID- 9928655
TI  - Reflex sympathetic dystrophy in a 12-year-old twin with comorbid conversion
      disorder in both twins.
AB  - A case of reflex sympathetic dystrophy is presented in a 12-year-old girl with
      comorbid conversion disorder. Her identical twin also had a conversion disorder.
      This is the first reported case of coexistence of reflex sympathetic dystrophy
      and conversion disorder. It is important for clinicians to be aware that these
      conditions may coexist since the presentation of symptoms differ, even though
      there are shared features of treatment.

PMID- 9928656
TI  - Community acquired fulminant Pseudomonas infection of the gastrointestinal tract
      in previously healthy infants.
AB  - Three previously healthy infants presented with diarrhoea and pyrexia and
      deteriorated rapidly. Two patients had necrotizing bowel disease requiring
      aggressive surgical intervention. All survived. P. aeruginosa gastrointestinal
      infection in previously healthy children is an extremely rare condition with a
      high mortality. Ecthyma gangrenosum was present in over 60% of reported cases
      although often not recognized initially. A high index of clinical suspicion,
      including prompt recognition of ecthyma gangrenosum, is mandatory for an early
      diagnosis of P. aeruginosa gastrointestinal infection. Early diagnosis and
      treatment may improve the prognosis.

PMID- 9928657
TI  - The athlete's heart: is this an entity in paediatrics?
AB  - A case report of a boy who demonstrates features of an athlete's heart,
      associated with dilatation of the coronary artery, is presented. The importance
      of distinguishing this benign condition from pathologic causes such as
      cardiomyopathy, and risk of sudden death in these athletes is discussed.

PMID- 9928658
TI  - Immunisation rates in child care children.

PMID- 9928659
TI  - Communication from a computerized emergency department to general practitioners.

PMID- 9928660
TI  - Regional variations in normal value for urinary calcium excretion.

PMID- 9928661
TI  - Type of medication used in children attending childcare in western Australia.

PMID- 9928662
TI  - Acute epiglottis.

PMID- 9928663
TI  - Controlled ethyl tert-butyl ether (ETBE) exposure of male volunteers. I.
      Toxicokinetics.
AB  - Ethyl tert-butyl ether (ETBE) might replace methyl tert-butyl ether (MTBE), a
      widely used additive in unleaded gasoline. The aim of this study was to evaluate
      uptake and disposition of ETBE, and eight healthy male volunteers were exposed to
      ETBE vapor (0, 5, 25, and 50 ppm) during 2 h of light physical exercise. ETBE and
      the proposed metabolites tert-butyl alcohol (TBA) and acetone were analyzed in
      exhaled air, blood, and urine. Compared to a previous MTBE study (A. Nihlen et
      al., 1998b, Toxicol. Appl. Pharmacol. 148, 274-280) lower respiratory uptake of
      ETBE (32-34%) was seen as well as a slightly higher respiratory exhalation (45
      50% of absorbed ETBE). The kinetic profile of ETBE could be described by four
      phases in blood (average half-times of 2 min, 18 min, 1.7 h, and 28 h) and two
      phases in urine (8 min and 8.6 h). Postexposure half-times of TBA in blood and
      urine were on average 12 and 8 h, respectively. The 48-h pulmonary excretion of
      TBA accounted for 1.4-3.8% of the absorbed ETBE, on an equimolar basis. Urinary
      excretion of ETBE and TBA was low, below 1% of the ETBE uptake, indicating
      further metabolism of TBA or other routes of metabolism and elimination. The
      kinetics of ETBE and TBA were linear up to 50 ppm. Based upon blood profile,
      levels in blood and urine, and kinetic profile we suggest that TBA is a more
      appropriate biomarker for ETBE than the parent ether itself. The acetone level in
      blood was higher after ETBE exposures compared to control exposure, and acetone
      is probably partly formed from ETBE.

PMID- 9928664
TI  - Kinetics of tissue distribution and elimination of pyrene and 1-hydroxypyrene
      following intravenous administration of [14C]pyrene in rats.
AB  - The tissue distribution and elimination of pyrene and 1-hydroxypyrene (1-OHP)
      were evaluated in male Sprague-Dawley rats (210-240 g) following an intravenous
      injection of 50 micromol/kg of [14C]pyrene. Blood and tissues were removed and
      urine and feces were collected at 1, 2, 4, 8, 16, and 24 h postdosing.
      [14C]Pyrene equivalents were measured by liquid scintillation counting, and beta
      glucuronidase/arylsulfatase-treated blood, tissues, and excreta were analyzed for
      pyrene and 1-OHP by HPLC/fluorescence. At 1 h, the largest fraction of the dose
      was found in adipose tissue, essentially as pyrene, and its elimination followed
      first-order monophasic kinetics with a half-life (t(1/2)) of 4.9 h. In blood,
      liver, kidney, lung, muscle, and gastrointestinal (GI) tract, kinetics of
      [14C]pyrene equivalents were biphasic and average t(1/2) values for the terminal
      elimination phase (8 to 24 h) ranged between 6.2 and 8.7 h. Elimination of pyrene
      in blood and these tissues except the GI tract followed first-order biphasic
      kinetics with average t(1/2) values of the terminal phase ranging between 3.6 and
      5.4 h. In the GI tract, a monophasic elimination kinetics of pyrene was observed
      with mean t(1/2) value of 3.1 h. Kinetics of 1-OHP in blood and liver showed a
      monophasic elimination with mean t(1/2) values of 6.7 and 6.2 h, respectively.
      Kinetics of 1-OHP in the other tissues were biphasic with average t(1/2) values
      of the terminal elimination phase ranging between 5.2 and 6.2 h. At 24 h, on
      average, 81.7% of the dose was recovered in the urine (57.2%), feces (18.3%), and
      GI tract (6.2%) as [14C]pyrene equivalents with 2.7 and 1.9% of dose excreted as
      total 1-OHP in urine and feces, respectively. At all time points, 1-OHP in urine
      represented a constant fraction of total 14C in urine and feces. These results
      indicate that (i) [14C]pyrene was rapidly distributed, metabolized, and
      eliminated from the body, and (ii) although 1-OHP represents a small percentage
      of total pyrene eliminated from the body, it remains a reliable indicator of
      systemic exposure to, and overall elimination of the 14C associated with, this
      polycyclic aromatic hydrocarbon.

PMID- 9928665
TI  - Chronic dietary toxicity/oncogenicity studies on 2,4-dichlorophenoxybutyric acid
      in rodents.
AB  - 2,4-Dichlorophenoxybutyric acid (2,4-DB) is principally used in the United States
      on peanuts, soybeans, and alfalfa. In Europe, it is used on cereals, undersown
      cereals, lucerne (alfalfa), clover, and clover mixtures. Doses in the 2-year
      chronic/oncogenicity rat study were 0, 60, 600, and 1800 ppm. No evidence of an
      oncogenic potential for 2,4-DB was evident and the study clearly established a
      NOEL of 2.48 mg/kg/day (60 ppm, males) and 3.23 mg/kg/day (60 ppm, females), as
      well as an MTD of 78.0 (1800 ppm, males) and 110.6 mg/kg/day (1800 ppm, females),
      for chronic effects of 2,4-DB in the rat. Doses in the 18-month mouse
      oncogenicity study were 0, 25, 250, and 750 ppm. No oncogenic effect was noted in
      the study. In summary, the findings of these studies indicate low chronic
      toxicity of 2,4-DB and the lack of oncogenic response to 2,4-DB following chronic
      dietary exposure of 2,4-DB in the rat and mouse.

PMID- 9928666
TI  - Dose-response examination of UDP-glucuronosyltransferase inducers and their
      ability to increase both TGF-beta expression and thyroid follicular cell
      apoptosis.
AB  - Exposure to certain microsomal enzyme inducers that increase UDP
      glucuronosyltransferase (UDP-GT) activity decreases thyroid hormone levels, which
      may lead to a subsequent increase in thyroid-stimulating hormone (TSH). This
      elevation of serum TSH has many effects on the thyroid, including increasing
      thyroid follicular cell proliferation, leading to hyperplasia. While induction of
      UDP-GT activity decreases thyroid hormone levels by enhancing biotransformation
      and subsequent biliary secretion, only certain UDP-GT inducers exhibit the
      ability to increase serum TSH levels. For example, phenobarbital (PB) and
      pregnenolone-16alpha-carbonitrile (PCN) increase serum levels of TSH, while 3
      methylcholanthrene (3MC) and Aroclor 1254 (PCB) do not. Increased serum TSH
      concentration also enhances thyroid gland expression of TGF-beta1, an anti
      proliferative, pro-apoptotic protein. In a previous study in our laboratory, rats
      were treated for various times (up to 90 days) with PB and PCN, which increased
      TGF-beta1 protein and apoptosis. The present study was designed to examine the
      dose-response effect of TSH-increasing (PB and PCN) and nonincreasing (3MC and
      PCB) UDP-GT inducers on apoptosis and TGF-beta1. PB and PCN, UDP-GT inducing
      compounds which increase serum TSH, increased the percentage of TGF-beta1
      positive follicular cells and increased apoptosis. In contrast, UDP-GT inducers
      that did not increase TSH (3MC and PCB) did not alter cell death or TGF-beta
      production. These data suggest that the increase of TGF-beta by TSH may serve to
      regulate the growth of hyperplastic thyroid.

PMID- 9928667
TI  - Acetaminophen alters estrogenic responses in vitro: stimulation of DNA synthesis
      in estrogen-responsive human breast cancer cells.
AB  - A limited number of studies have investigated the estrogenic potential of
      acetaminophen but none has reported its effects on breast cells. Many compounds
      that alter estrogen-mediated processes in various tissues contain p-phenolic
      moieties. Acetaminophen is a commonly used analgesic/antipyretic that also
      contains a p-phenol. This study tested the hypothesis that therapeutic
      concentrations of acetaminophen alter estrogen-responsive human breast cancer
      cell DNA synthesis. To this end, a modified E-screen assay was developed to
      determine the response to acetaminophen of two dichotomous types of human breast
      cancer cell lines: estrogen-responsive (MCF7, T47D, ZR-75-1) and estrogen
      nonresponsive (MDA-MB-231, HS578T). Cells were placed in estradiol-free medium
      and then exposed to 3 nM estradiol or 0.03-1 mM acetaminophen. The proliferative
      response was assessed by determining [3H]thymidine incorporation into DNA and by
      determining the percentage of cells in the DNA synthesis (S) phase of the cell
      cycle. Concentrations of acetaminophen commonly attained in human plasma with
      therapeutic doses of this drug (approximately 0.1 mM) were found as effective as
      estradiol in stimulating DNA synthesis in estrogen-responsive breast cancer
      cells. Higher acetaminophen concentrations (1 mM) stimulated estrogen-responsive
      cells to a lesser extent. The combination of estradiol and acetaminophen did not
      stimulate DNA synthesis in estrogen-responsive cells more than either agent
      alone. Neither acetaminophen nor estradiol stimulated DNA synthesis in estrogen
      nonresponsive human breast cancer cells. These novel findings demonstrate that
      therapeutic acetaminophen concentrations specifically stimulate estrogen
      responsive breast cancer cell DNA synthesis, suggesting that this drug may exert
      estrogenic effects.

PMID- 9928668
TI  - An ongoing validation of a Tier I screening battery for detecting endocrine
      active compounds (EACs).
AB  - After previously examining an estrogen receptor agonist (17beta-estradiol),
      several additional compounds have been evaluated in a Tier I screening battery
      for detecting endocrine-active compounds (EACs): an estrogen receptor antagonist
      (ICI-182,780, ICI), an androgen receptor antagonist (flutamide, FLUT), a
      testosterone biosynthesis inhibitor (ketoconazole, KETO), a 5alpha-reductase
      inhibitor (finasteride, FIN), and an aromatase inhibitor (anastrozole, ANA). The
      Tier I battery incorporates two short-term in vivo tests (a 5-day ovariectomized
      female battery and a 15-day intact male battery) and an in vitro yeast
      transactivation system (YTS). The Tier I battery is designed to identify
      compounds that have the potential to act as agonists or antagonists to the
      estrogen, androgen, progesterone, or dopamine receptors, steroid biosynthesis
      inhibitors (aromatase, 5alpha-reductase, and testosterone biosynthesis), or
      compounds that alter thyroid function. ICI administration decreased uterine
      estrogen and progesterone receptor number in the female battery, increased serum
      follicle-stimulating hormone (FSH) levels and caused spermatid retention in the
      male battery, and activated gene transcription in the YTS containing the estrogen
      receptor. FLUT administration increased uterine stromal cell proliferation in the
      female battery and decreased weights for all androgen-dependent tissues, induced
      Leydig cell hyperplasia, and caused hormonal alterations (increased testosterone
      (T), estradiol (E2), dihydrotestosterone (DHT), luteinizing hormone (LH), and
      FSH) in the male battery, and competed for binding to the androgen receptor in
      the YTS competition assay. In the male battery KETO decreased weights for all
      androgen-dependent tissues, caused hormonal alterations (decreased T and DHT and
      increased LH and FSH), and induced spermatid retention. FIN decreased seminal
      vesicle and accessory sex gland (ASG) unit weight and caused hormonal alterations
      (decreased DHT and increased LH, and PRL) in the male battery. KETO was judged
      not to affect any of the endpoints in the female battery. ANA decreased ASG unit
      weight and serum E2 levels in the male battery. Using the responses obtained for
      all the endpoints in the Tier I battery, a distinct "fingerprint" was produced
      for each type of endocrine activity against which compounds with unknown activity
      can be compared. These data demonstrate that the described Tier I battery is
      useful for identifying EACs.

PMID- 9928669
TI  - Ex vivo and in vitro testis and ovary explants: utility for identifying steroid
      biosynthesis inhibitors and comparison to a Tier I screening battery.
AB  - Testis and ovary explants have been proposed as in vitro screens for identifying
      potential inhibitors of steroid biosynthesis. The goals of the current study were
      to optimize the conditions of the two assays, to characterize these assays using
      several compounds with well-defined endocrine activity, and to compare the
      responses from the explant assays with an in vivo male battery currently
      undergoing validation using the Crl:CD BR rat in order to evaluate their utility
      as test systems for screening unknown compounds for possible steroid biosynthesis
      inhibition activity. There were two components to the testis/ovary assays: ex
      vivo and in vitro. The ex vivo component used testes/ovaries from animals dosed
      with the test compounds in vivo, and the in vitro component used testes/ovaries
      from control animals. For the testis assays, decapsulated testis explants (50 mg)
      were placed into glass scintillation vials, +/-1.0 IU/ml hCG for 3 h in a shaking
      water bath (34 degrees C). Following the incubation period, medium was removed,
      centrifuged, and frozen until assayed for hormone concentrations. A similar
      procedure was used for the ovary explant assay except that each ovary was
      incubated separately. The testis explants were evaluated using the following
      compounds: ketoconazole (KETO), a testosterone biosynthesis inhibitor;
      aminoglutethimide (AG) (only in vitro) and anastrozole (ANA), aromatase
      inhibitors; finasteride (FIN), a 5alpha-reductase inhibitor; 17beta-estradiol
      (17beta-E2), an estrogen receptor agonist; flutamide (FLUT), an androgen receptor
      antagonist; ICI-182,780 (ICI), an estrogen receptor antagonist; haloperidol
      (HALO), a D2 receptor antagonist; and reserpine (RES), a dopamine depletor. In
      the ovary assay, AG (only in vitro), ANA, ICI, and HALO (only in vitro) were
      evaluated. Addition of fetal calf serum to the medium allowed measurement of
      estradiol (E2) in the testis assay, but production was not inhibited by ANA or
      AG. In the ovary explant assay, only AG was identified as inhibiting E2
      production in vitro. Hence, both the testis and ovary explant assays appear to
      have limited utility for detecting aromatase inhibitors. Screening of these nine
      diverse endocrine-active compounds resulted in all of them being identified as
      altering the endocrine system when assessed by ex vivo and in vitro testis
      explants. Using only the in vitro assessment with the criteria of steroid
      biosynthesis inhibition, four of nine compounds were correctly identified in the
      testis explant assay (17beta-E2, KETO, FLUT, and HALO). The predictability of
      both the in vitro and ex vivo ovary assay was 50%, suggesting a 50% false
      positive or negative rate with unknown compounds. However, of the seven compounds
      assessed to date (17beta-E2, ICI, ANA, KETO, FLUT, HALO, and RES), all were
      correctly identified using an in vivo male battery, which also has the capability
      to detect other endocrine activities. Therefore, the testis and ovary explant
      assay would not be necessary if one were using an in vivo male battery, since
      this screen would identify steroid biosynthesis inhibitors and would also
      identify several other endocrine activities. Because of the difficulties in
      assessing cytotoxicity and the high false positive/negative rates, the ovary and
      testis explant assays are not useful as routine screening procedures for
      detecting steroid biosynthesis inhibitors; however, they may have utility in
      confirming in vivo findings.

PMID- 9928670
TI  - Evaluation of the primary humoral immune response following exposure of male rats
      to 17beta-estradiol or flutamide for 15 days.
AB  - There is a concern that certain industrial chemicals found in the environment may
      mimic or antagonize endogenous hormones and adversely affect the endocrine as
      well as the immune system. The objective of this study was to determine if
      exposure of Crl:CD (SD)BR male rats to 17beta-estradiol (17beta-E2), an estrogen
      receptor agonist, or flutamide (FLUT), an androgen receptor antagonist, would
      significantly alter the primary IgM humoral immune response to sheep red blood
      cells (SRBC). This study was conducted in the context of a male in vivo Tier I
      battery designed to identify endocrine-active compounds (EACs). The Tier I male
      battery consists of organ weights coupled with a comprehensive hormonal
      assessment. Rats were dosed by the intraperitoneal route for 15 days with vehicle
      or 0.001, 0.0025, 0.0075, or 0.050 mg/kg/day 17beta-E2 or 0.25, 1, 5, or 20
      mg/kg/day FLUT. Six days prior to termination, selected rats were injected
      intravenously with SRBC for assessment of humoral immune function. Spleen cell
      number and spleen and thymus weights were obtained. Serum was analyzed for anti
      SRBC IgM antibody by using an enzyme-linked immunosorbent assay. At 0.050
      mg/kg/day 17beta-E2, mean final body and absolute thymus weights were
      significantly decreased to 84 and 65% of control, respectively. 17beta-E2 did not
      significantly alter spleen weight, spleen cell number, or the primary IgM humoral
      immune response to SRBC. The no-observed-adverse-effect level (NOAEL) for immune
      system alteration was 0.050 mg/kg/day 17beta-E2 since the decrease in absolute
      thymus weight was judged to be secondary to the decrements in body weight. In the
      Tier I male battery, responses to 17beta-E2 included decreased absolute testis
      and epididymis weights, decreased relative accessory sex gland unit weights,
      hormonal alterations (decreased serum testosterone (T), dihydrotestosterone
      (DHT), and luteinizing hormone (LH), and increased serum prolactin and E2
      levels). The lowest-observed-adverse-effect level (LOAEL) for the reproductive
      indices was 0.001 mg/kg/day 17beta-E2 based on the hormonal alterations seen at
      this level; no NOAEL was established. Exposure to FLUT did not significantly
      alter mean final body, spleen, or absolute thymus weights, spleen cell number, or
      the primary IgM humoral immune response to SRBC. A significant increase (118% of
      control) in relative thymus weight was observed at 20 mg/kg/day FLUT. The NOAEL
      for immune system alteration was 5 mg/kg/day FLUT based on the increased relative
      thymus weights that were judged to be compound-related. In the Tier I male
      battery, responses to FLUT included decreased absolute epididymis and relative
      accessory sex gland unit weights and hormonal alterations (increased serum T,
      DHT, E2, and LH, and decreased follicle stimulating hormone levels). The LOAEL
      for the reproductive indices was 0.25 mg/kg/day FLUT based on the hormonal
      alterations seen at this level; no NOAEL was established. Based on these data,
      the reproductive and not the immune system appears to be the primary target organ
      of toxicity in young adult male rats treated with either 17beta-E2 or FLUT.

PMID- 9928671
TI  - Investigation of the induction of DNA double-strand breaks by methylenediphenyl-4
      4'-diisocyanate in cultured human lung epithelial cells.
AB  - The question was addressed whether methylenediphenyl-4,4'-diisocyanate (MDI), a
      bifunctional electrophile, can induce DNA double-strand breaks (DSB) by repair of
      interstrand DNA crosslinks or whether DSB are the result of cell death. Cultured
      human lung epithelial cells (A549) were treated with MDI, methylene-4,4'
      dianiline (MDA; a potential hydrolysis product of MDI), the nitrogen mustard
      melphalan, and the detergent Triton X-100. All chemicals were dissolved in
      ethylene glycol dimethyl ether which was added to a cell monolayer covered with
      phosphate-buffered saline. After 2 h, the treatment solution was exchanged
      against medium, and 8, 24, and 72 h after treatment initiation, the induction of
      DNA double-strand breaks was assessed by pulsed-field gel electrophoresis. At the
      same time, the viability was determined with the MTT test (intracellular
      reduction of the tetrazolium dye MTT). At the 8-h time point, 1 and 10 microM
      melphalan induced DSB without concomitant effect on cell viability. With all
      other chemicals, the dose-response curves for DNA fragmentation and viability
      were mirror images. Approximate 50% lethal concentrations were 200, 3000, and 100
      microM for MDI, MDA, and Triton X-100, respectively. For these chemicals, the
      observed DSB were the consequence of extragenomic damage in the course of cell
      death rather than of an interaction with DNA. The mechanistic difference of
      melphalan was supported by analysis of nuclear morphology. Apoptotic bodies were
      observed only after melphalan treatment, whereas MDI and Triton X-100 produced
      only irregular clumping of chromatin (72-h time point). DNA fragment length
      analysis showed a time-independent pattern, with sizes between 1 and 4 Mbp for
      melphalan, while MDI, and Triton X-100 induced smaller DNA fragments in a time
      dependent manner. It is concluded that DSB observed in cells treated with MDI are
      unlikely the result of DNA crosslink formation.

PMID- 9928672
TI  - Analysis of Pb2+ entry into cultured astroglia.
AB  - Astroglia serve as a presumptive lead (Pb) sink in the brain; therefore, this
      study examined Pb entry into cultured rat astroglia utilizing the Ca2+
      fluorophore indo-1 as a tool for detecting Pb2+ entry during acute exposure. The
      interactions of Pb2+ with indo-1 were analyzed by fluorescence spectrophotometry
      in a cell-free system. The emission spectrum of Pb2+/indo-1 was substantially
      different from that of Ca2+/indo-1 due to suppression of indo-1 fluorescence
      emission intensity. Next, we established the presence of L-type Ca2+ channels in
      astroglial cultures and demonstrated that Pb accumulation is enhanced under serum
      free conditions and by the application of Bay-K 8644. Because acute exposure is
      of less toxicologic relevance than repeated low-level exposure, we then examined
      Pb uptake in cultures treated for up to 1 week with Pb. AAS revealed that Pb
      accumulation was accompanied by an increase in total cellular [Ca]. In addition,
      differences in basal indo-1 fluorescence levels and differences in responsiveness
      to ionomycin were observed. Ionomycin induced an increase in the fluorescence
      ratio in untreated cells but cells treated for 1 day with Pb showed no response
      to ionomycin. However, cells treated for 3 and 7 days showed a partial response
      to ionomycin. TPEN was used to evaluate the interactions of Pb2+ with indo-1 and
      only cells treated for 7 days showed a response to TPEN. Thus, the present study
      characterizes Pb2+ entry into astroglia via L-type Ca2+ channels and presents the
      possibility of using indo-1 for analysis of Pb2+ uptake and the subsequent
      neurotoxic events in astroglia.

PMID- 9928673
TI  - Learning and memory of rats after long-term administration of low doses of
      parathion.
AB  - A set of four learning and memory tests (Morris Maze I for reference memory,
      Morris Maze II for working memory, one-way active avoidance, and passive
      avoidance) were employed to address the questions whether parathion impaired
      cognitive functions after low, long-term exposure and could cause persistent
      changes in cognition. Motor activity and general behavior were investigated in a
      functional observational battery. Parathion was administered in rat food in low
      doses which caused no clinical symptoms and no or borderline brain
      acetylcholinesterase inhibition. Parathion doses of 0.5, 2, or 8 ppm in rat food
      produced the averaged uptake of 24, 100, or 400 microg/kg body weight per group
      per day in male rats and 36, 152, or 550 microg/kg per day in female rats in week
      13. Learning tests were performed in weeks 1 to 4 and 10 to 14, as well as 30 to
      34 weeks after the end of treatment, when the male and female rats were about 13
      months old. Low doses of parathion given daily for 13 weeks had no cumulative or
      adverse effects on learning and memory, either during treatment or after the
      extended treatment-free period, in any of the tests. A significant improvement of
      learning compared to control observed in the Morris Water Maze I during the first
      week of treatment (males dose group 0.5 ppm) shows that parathion can improved
      cognitive functions in rats. Results of the study indicate that adverse effects
      changing learning and memory in animals may occur only at higher doses of
      organophosphates, at which the peripheral and brain acetylcholinesterases are
      inhibited to a greater extent than those in the present study.

PMID- 9928674
TI  - Modulation of sulfur mustard toxicity by arginine analogues and related nitric
      oxide synthase inhibitors in vitro.
AB  - The modulating effects of a series of arginine analogues and related nitric oxide
      synthase inhibitors against the toxicity of sulfur mustard (HD) in primary
      cultures of chick embryo forebrain neurons were examined. In addition to the
      previously identified protective compounds, D- and L-nitroarginine methyl ester,
      eight additional arginine analogues were shown to have significant, concentration
      dependent protective characteristics against HD toxicity. Of these, L
      nitroarginine was the most potent, increasing the LC50 of vehicle-pretreated HD
      treated control cultures by approximately 350%. In addition to these protective
      agents, five compounds related to arginine were also identified that potentiated
      the toxicity of HD in the neuron cultures in a concentration-dependent manner.
      This action occurred at concentrations where these chemicals alone exhibited no
      toxicity. Characterization of the active compounds in this study showed that it
      was likely that the protective agents, as well as those compounds that
      potentiated HD toxicity, were exerting their effects at the same biochemical
      target, but not through the inhibition of nitric oxide synthase. Although the
      identity of this target site is as yet unknown, these studies demonstrate that
      subtle alterations to the arginine structure can yield compounds that
      differentially modulate the toxicity of HD through their activity at a common
      target site.

PMID- 9928675
TI  - Evaluation of the developmental toxicity of methacrylamide and N,N'
      methylenebisacrylamide in Swiss mice.
AB  - Timed-pregnant CD-1 outbred albino Swiss mice received either methacrylamide
      (MAC; 0, 60, 120, or 180 mg/kg/day) or N,N'-methylenebisacrylamide (BAC; 0, 3,
      10, or 30 mg/kg/day) p.o. in distilled water on gestational days (GD) 6 through
      17. Maternal clinical status was monitored daily. At termination (GD 17),
      confirmed-pregnant females (27-30 per group, MAC; 24-25 per group, BAC) were
      evaluated for clinical status and gestational outcome; live fetuses were examined
      for external, visceral, and skeletal malformations. For MAC, no treatment-related
      maternal mortality was observed. Maternal body weight on GD 17, maternal weight
      gain during treatment and gestation, and corrected maternal weight gain were
      reduced at the high dose. Relative maternal food and water intake was not
      adversely affected; neurotoxicity was not observed. Relative maternal liver
      weight was increased at > or = 120 mg/kg/day; gravid uterine weight was decreased
      at 180 mg/kg/day. The maternal no-observed adverse effect level (NOAEL) was 60
      mg/kg/day. The NOAEL for developmental toxicity was also 60 mg/kg/day. At > or =
      120 mg/kg/day, mean fetal body weight was reduced. At 180 mg/kg/day, increased
      postimplantation death per litter was observed. Morphological development was not
      affected. The maternal NOAEL for BAC was 10 mg/kg/day. At 30 mg/kg/day, decreased
      maternal body weight on GD 17, maternal body weight change during treatment and
      gestation, corrected maternal body weight, and gravid uterine weight were
      observed. Relative maternal liver weight increased at 30 mg/kg/day. The
      developmental NOAEL was 3 mg/kg/day BAC. Mean fetal body weight was reduced at 30
      mg/kg/day. At > or = 10 mg/kg/day, an increased incidence of fetal variations
      (extra rib) was observed, although fetal malformation rate was unaffected. MAC
      and BAC were not teratogenic to Swiss mice at the doses tested. BAC was more
      potent than MAC in causing adverse maternal and developmental effects.

PMID- 9928676
TI  - Chronic dietary toxicity study on 2,4-dichlorophenoxybutyric acid in the dog.
AB  - 2,4-Dichlorophenoxybutyric acid (2,4-DB) is principally used in the United States
      as a herbicide on peanuts, soybeans, and alfalfa. In Europe, it is used on
      cereals, undersown cereals, lucerne (alfalfa), clover, and clover mixtures. A 1
      year chronic toxicity study in the dog was performed on 2,4-DB. Doses in the
      study of 0, 75, 225, and 450 ppm were administered to six animals/sex/group. The
      top dose was reduced from 675 ppm during week 7 of the study due to body weight
      loss and decreased food consumption. Four animals/sex/group were euthanized after
      52 weeks of treatment and two animals/sex/group were placed on control diet for 4
      weeks and euthanized at week 56. Treatment-related findings included reductions
      in body weight gain and food consumption, and minor increases in inorganic
      phosphorus, blood urea nitrogen, creatinine, aspartate aminotransferase, and
      alanine aminotransferase. After the 4-week recovery period, the only parameter
      that did not return to control levels was the aspartate aminotransferase. Gross
      pathology evaluation noted distended gallbladders and decreased organ weights
      were noted in females for the adrenal, spleen, and ovaries. Histologically, the
      liver and kidney were the target organs. The data from the study support a
      chronic no observed adverse effect level of 75 ppm (2.39 and 2.15 mg/kg/day for
      males and females, respectively) for 2,4-DB. There was no indication of any
      immunotoxic or oncogenic response in the studies. In conclusion, the findings in
      this study indicate the general low toxicity of 2,4-DB following chronic dietary
      exposure in the dog.

PMID- 9928677
TI  - Controlled ethyl tert-butyl ether (ETBE) exposure of male volunteers. II. Acute
      effects.
AB  - The aim of this study was to evaluate acute effects of ethyl tert-butyl ether
      (ETBE) in man after short-term exposure. ETBE may in the future replace methyl
      tert-butyl ether, a widely used oxygenate in unleaded gasoline. Eight healthy
      male volunteers were exposed to ETBE vapor for 2 h at four levels (0, 5, 25, and
      50 ppm) during light physical exercise. The subjects rated irritative symptoms,
      discomfort, and central nervous system effects in a questionnaire. Ocular (eye
      redness, tear film break-up time, conjunctival epithelial damage, and blinking
      frequency), nasal (acoustic rhinometry and analysis of inflammatory markers and
      cells in nasal lavage fluid), and pulmonary (peak expiratory flow, forced
      expiratory volume in 1 s, forced vital capacity, vital capacity, and transfer
      factor) measurements were performed. Significantly increased ratings of solvent
      smell (p = 0.001, repeated-measures ANOVA) were seen during exposures and
      correlated to exposure levels. Furthermore, significantly elevated ratings of
      discomfort in throat and airways were seen during and after 50 ppm compared to
      the control exposure (p = 0.02). Increased nasal swelling (p = 0.001) and
      blinking frequency (p = 0.01) were noted at all exposure levels, but their
      magnitudes were not related to exposure levels. A slightly impaired pulmonary
      function was seen at 25 and 50 ppm, since forced vital capacity (p = 0.02) and
      vital capacity (p = 0.04) differed significantly from the clean air exposure.
      Although the impairments seemed to fall within normal inter- and intraindividual
      variation and have no clinical relevance as such, it cannot be excluded that
      other individuals may react more severely than eight healthy male volunteers in
      this study.

PMID- 9928678
TI  - Altered hemostasis in male rats following administration of the ACAT inhibitor
      SKF-99085.
AB  - SKF-99085, an acyl-CoA:cholesterol acyltransferase (ACAT) was evaluated in male
      and female Sprague-Dawley rats at oral doses of 0, 10, 100, or 400 mg/kg/day for
      6 months as part of the preclinical safety assessment of this drug candidate. In
      male rats given 400 mg/kg/day SKF-99085, hemorrhage and death were observed in
      males during the first month of the study, prompting collection of blood samples
      at weeks 6, 17, and 24 to monitor coagulation parameters. A dose-related increase
      in activated partial thromboplastin time (APTT) and Thrombotest clotting time
      (TCT) was observed in all male drug-treated groups. Mean APTT values for male
      rats given 10, 100, or 400 mg/kg/day were increased maximally to 17.5, 20.8, and
      34.7 s (control, 15.4-16.0 s), and mean TCT values were increased to 86, 100, and
      >300 s (control, 71-74 s), respectively. Mean prothrombin times (PT) for male
      rats given 400 mg/kg/day were increased to 16.5 s (control, 12.9-13.1 s).
      Activities of factors II, VII, IX, and X were decreased in males at dosages of
      10, 100, or 400 mg/kg/day. Factor V and VIII activities were unaffected. In
      summary, the drug-related hemorrhagic disorder observed in male rats given high
      doses of the ACAT inhibitor SKF 99085 was attributed to a reduction in the
      activity of vitamin-K-dependent coagulation factors. In contrast to humans and
      some other species, the APTT and TCT were more sensitive than the PT in detecting
      this effect.

PMID- 9928679
TI  - Comparative intravenous toxicity of cisplatin solution and cisplatin encapsulated
      in long-circulating, pegylated liposomes in cynomolgus monkeys.
AB  - The toxicity of cisplatin encapsulated in pegylated, long-circulating liposomes
      (SPI-077) was compared with nonliposomal cisplatin in male and female cynomolgus
      monkeys (n = 2-4 per sex per group) treated with intravenous infusions of 2.5 or
      25 mg/kg SPI-077, 2.5 mg/kg cisplatin, placebo liposomes, or saline once every 3
      weeks for total of five treatments. All animals survived until scheduled necropsy
      at 3 days after the final treatment or after a treatment-free 4-week recovery
      period. Emesis occurred after each treatment in all cisplatin-treated monkeys,
      but only once in one monkey treated with high-dose SPI-077. Dose-related mild
      decreases in red blood cell (RBC) count, hemoglobin, and hematocrit to or
      slightly below low normal range occurred in the high-dose SPI-077 and placebo
      liposome treatment groups after each treatment, with partial to complete recovery
      between treatments and no signs of correlating bone marrow toxicity. Decreases
      were similar in cisplatin-treated monkeys, but resolved only slightly between
      treatments and after the end of treatment (continuing to decrease in females) and
      were accompanied by bone marrow hypocellularity. Indirect, but not direct,
      bilirubin levels were cyclically elevated in the high-dose SPI-077 and placebo
      treated animals, but not in the other treatment groups. Levels had either fully
      resolved or were near baseline and/or saline group values prior to the next
      treatment. Serum cholesterol levels were cyclically increased in SPI-077- and
      placebo liposome-treated animals, and minimally increased numbers of foam cells
      were seen in the liver, spleen, kidney, and other organs; both were considered
      related to the lipid dose administered. Cisplatin-treated monkeys exhibited
      sensory polyneuropathy and moderate irreversible toxic tubular nephrosis, but no
      neuropathy or nephrotoxicity was seen in either SPI-077 treatment group.
      Microscopically, treatment-related cell death was seen in dorsal root ganglia
      (DRG), affecting 15% of the cells in cisplatin-treated animals, compared to 8 and
      12% in the low- and high-dose SPI-077 treatment groups. Neither drug was
      ototoxic. In summary, repeated administration of SPI-077 produced minimal,
      reversible effects related to the lipid dose administered, mostly limited to the
      25 mg/kg dose group. The most notable effects in this group were cyclical
      decreases in hematology parameters thought to be related to increased recycling
      of a small fraction of RBCs and limited cell death in the DRG in the absence of
      any neurophysiological changes. Animals treated with a 10-fold lower dose of
      cisplatin (2.5 mg/kg), in contrast, exhibited myelo-, nephro-, and neurotoxicity,
      including sensory neuropathy, and were emetic after every dose. The SPI-077
      liposomal formulation of cisplatin may provide a less toxic alternative to
      standard cisplatin solution.

PMID- 9928680
TI  - Different patterns of kidney toxicity after subacute administration of Na
      nitrilotriacetic acid and Fe-nitrilotriacetic acid to Wistar rats.
AB  - Na-nitrilotriacetic acid (Na3NTA) and Fe-nitrilotriacetic acid (FeNTA) have both
      been described to cause tumors in the urinary tract of rodents. However, these
      effects were observed using different modes of administration at extremely
      different dose levels and explained by different mechanisms. Whereas FeNTA causes
      an iron overload of cells and is genotoxic in various assays, Na3NTA is
      predominantly bound to zinc in vivo and thereby causes cytotoxic effects in the
      urinary tract. In contrast to FeNTA, Na3NTA requires high dose levels to produce
      tumors. The aim of this study was to compare the effects of Na3NTA and FeNTA on
      cellular proliferation, histopathology, lipid peroxidation, and 8-OH-2'
      deoxyguanosine levels in the kidneys as well as on the urinary excretion of Ca,
      Fe, and Zn. For evaluation of DNA synthesis both compounds were administered for
      1 or 4 weeks to 14-week-old male Wistar rats at a tumor causing dose, Na3NTA via
      the diet at 150 ppm and 20,000 ppm (approximately 9 and approximately 1000
      mg/kg/day) and FeNTA i.p. at 25 mg/kg/day. An osmotic minipump, containing 20
      mg/ml BrdU, was implanted subcutaneously 7 days before necropsy. Na3NTA showed
      nearly no effect on DNA replication after 1 week but a strong reaction after 4
      weeks. The increase was 10- to 18-fold in different renal compartments. The
      enhancement of proliferation in the proximal tubules was nearly twice that in the
      distal tubules. In contrast, FeNTA caused DNA replication during the first week,
      and this was restricted to the proximal tubules. After 4 weeks there was an 18
      fold increase in the outer stripe and no effect in the inner stripe of the outer
      medulla. The data presented give evidence to the assumption that both substances
      increase cell proliferation as a compensatory mechanism, causing different
      pattern of tubular proliferation in terms of time course and affected cell types.
      Both Na3NTA at 20,000 ppm and FeNTA led to increased lipid peroxidation, whereas
      increased levels of 8-OH-2'-deoxyguanosine were observed only after treatment
      with FeNTA. Urinary excretion of Zn was increased 30-fold after administration of
      20,000 ppm Na3NTA but only 2-fold after administration of FeNTA. Urinary
      excretion of Ca and Fe remained unchanged after treatment with either Na3NTA and
      FeNTA. These results show that the Na3NTA-related proliferative effects are not
      mediated by an internal formation of FeNTA.

PMID- 9928681
TI  - Alteration of Kupffer cell function and morphology by low melt point paraffin wax
      in female Fischer-344 but not Sprague-Dawley rats.
AB  - This study was conducted to compare the effects of 60-day dietary exposure (2%)
      to low melt point paraffin wax (LMPW) on both general liver morphology and
      Kupffer cell (KC) function and morphology in female F-344 and Sprague-Dawley (SD)
      rats. Livers from only F-344 rats fed LMPW had granuloma formation/lymphoid cell
      aggregates with small areas of necrosis. Significant increases in serum alanine
      and aspartate aminotransferase as well as gamma-glutamyltransferase activities
      were detected only in treated F-344 rats. Additionally, detectable amounts of
      LMPW were present only in livers of treated F-344 rats. Because KC can be
      involved in granuloma formation, their morphology and function were examined.
      Electron microscopy revealed the presence of large, irregularly shaped, membrane
      associated vacuoles in cells isolated from F-344 rats exposed to LMPW. These
      vacuoles were not seen in KC from control rats and rarely detected in KC isolated
      from LMPW-exposed SD rats. Moreover, indices of KC function including phagocytic
      activity and nitric oxide and superoxide anion production were significantly
      increased by KC isolated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold
      increases, respectively) over untreated controls. In contrast, LPS-stimulated
      production of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F
      344 rats. No significant changes in these functions were observed in KC isolated
      from SD rats exposed to LMPW or from KC isolated from control F-344 or SD rats.
      These data provide evidence that dietary LMPW alters the morphology and
      functional capacity of KC of F-344 but not SD rats and these changes may
      ultimately lead to granuloma formation.

PMID- 9928682
TI  - Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of
      methapyrilene.
AB  - The mechanisms by which the antihistamine drug methapyrilene causes acute
      periportal hepatotoxicity in rats are not yet elucidated. This study investigated
      the effects of modulators of cytochrome P450 (CYP) activity on the hepatotoxicity
      of methapyrilene and also the effect of methapyrilene on hepatic CYP.
      Pretreatment of male Han Wistar rats with beta-naphthoflavone, phenobarbitone,
      butylated hydroxytoluene, piperonyl butoxide, Aroclor 1254, or cobalt
      protoporphyrin IX, agents known to modify hepatic CYP, all afforded some degree
      of protection against a hepatotoxic dose of methapyrilene (150 mg/kg x 3 days
      p.o.), as assessed by clinical chemistry and histology. Total hepatic CYP
      depletion by cobalt protoporphyrin IX treatment indicated CYP-mediated
      bioactivation was a prerequisite for methapyrilene-induced hepatotoxicity.
      Protection against hepatic damage was strongly associated with beta
      naphthoflavone induction of CYP1A and phenobarbitone-associated CYP2B induction.
      However, the role of CYP3A, which is constitutively expressed in the liver and
      induced by piperonyl butoxide, butylated hydroxytoluene, or Aroclor 1254, was
      unclear. Modulation of FAD monooxgenase activity by methimazole pretreatment was
      not associated with increased methapyrilene-induced hepatotoxicity. Methapyrilene
      treatment alone specifically decreased microsomal enzyme activity markers for
      CYP2C11, CYP3A, and CYP2A and pretreatment with all the hepatic enzyme-inducing
      agents specifically prevented the loss of CYP2C11. Together this suggested that
      CYP2C11 was responsible for the suicide substrate bioactivation of methapyrilene
      and the toxicologic outcome largely relied upon an abundance of detoxifying
      enzymes present in the liver.

PMID- 9928683
TI  - Susceptibility of MT-null mice to chronic CdCl2-induced nephrotoxicity indicates
      that renal injury is not mediated by the CdMT complex.
AB  - Chronic human exposure to Cd results in kidney injury. It has been proposed that
      nephrotoxicity produced by chronic Cd exposure is via the Cd-metallothionein
      complex (CdMT) and not by inorganic forms of Cd. If this hypothesis is correct,
      then MT-null mice, which cannot form CdMT, should not develop nephrotoxicity.
      Control and MT-null mice were injected s.c. with a wide range of CdCl2 doses, six
      times/week for up to 10 weeks, and their renal Cd burden, renal MT concentration,
      and nephrotoxicity were quantified. In control mice, renal Cd burden increased in
      a dose- and time-dependent manner, reaching as high as 140 microg Cd/g kidney,
      along with 150-fold increases in renal MT concentrations, reaching 800 microg
      MT/g kidney. In MT-null mice, renal Cd concentration (10 microg/g) was much
      lower, and renal MT was nonexistent. The maximum tolerated dose of Cd in MT-null
      mice was approximately one-eighth that of controls. MT-null mice were more
      susceptible than controls to Cd-induced renal injury, as evidenced by increased
      urinary excretion of protein, glucose, gamma-glutamyltransferase, and N-acetyl
      beta-D-glucosaminidase, as well as by increased blood urea nitrogen levels.
      Kidneys of Cd-treated mice were enlarged and histopathology showed various types
      of lesions, including proximal tubular degeneration, apoptosis, atrophy,
      interstitial inflammation, and glomerular swelling. These lesions were more
      severe in MT-null than in control mice, mirroring the biochemical analyses. These
      data indicate that Cd-induced renal injury is not necessarily mediated through
      the CdMT complex and that MT is an important intracellular protein in protecting
      against chronic Cd nephrotoxicity.

PMID- 9928684
TI  - Phosphine-induced oxidative stress in Hepa 1c1c7 cells.
AB  - Phosphine (PH3), from hydrolysis of metal phosphides, is an important insecticide
      (aluminum phosphide) and rodenticide (zinc phosphide) and is considered genotoxic
      and cytotoxic in mammals. This study tests the hypothesis that PH3-induced
      genotoxicity and cytotoxicity are associated with oxidative stress by examining
      liver (Hepa 1c1c7) cells for possible relationships among cell death, increases
      in reactive oxygen species (ROS) and lipid peroxidation, and elevated 8
      hydroxyguanine (8-OH-Gua) in DNA. PH3 was generated from 0.5 mM magnesium
      phosphide (Mg3P2) to give 1 mM PH3 as the nominal and maximal concentration. This
      level causes 31% cell death at 6 h, measured by lactate dehydrogenase leakage,
      with appropriate dependence on concentration and time. The intracellular ROS
      level is elevated within 0.5 h following exposure to PH3, peaking at 235% of the
      control by about 1 h. Lipid peroxidation (measured as malondialdehyde plus 4
      hydroxyalkenals) is increased up to 504% by PH3 at 6 h in a time-dependent
      manner. The level of 8-OH-Gua in DNA, a biomarker of mutagenic oxidative DNA
      damage analyzed by GC/MS, increases to 259% at 6 h after PH3 treatment.
      Antioxidants significantly attenuate the PH3-induced ROS formation, lipid
      peroxidation, 8-OH-Gua formation in DNA, and cell death, with the general order
      for effectiveness of GSH (5 mM) and D-mannitol (10 mM) (hydroxyl radical
      scavengers), then Tempol (2.5 mM) and sodium azide (3 mM) (superoxide anion and
      singlet oxygen scavengers, respectively). These studies support the hypothesis
      that PH3-induced mutagenic and cytotoxic effects are due to increased ROS levels,
      probably hydroxyl radicals, initiating oxidative damage.

PMID- 9928685
TI  - Pediatric sedation with analgesia.
AB  - Sedation with analgesia is frequently required to perform painful or invasive
      procedures in children. The best medication combination for pediatric sedation
      with analgesia is yet to be identified. Sixty-four of 243 total sedation with
      analgesia procedures from January 1994 through August 1995 were randomly chosen
      for descriptive retrospective review and analysis. Four minor complications from
      the procedures were identified, and recovery was complete in all cases. One
      medication combination (fentanyl 1 microg/kg with propofol 1.5 to 2 mg/kg,
      followed by an infusion of 150 microg/kg/min) provided the shortest mean time to
      dismissal (17.8 minutes v 38 minutes) when compared with other combinations used.
      No episodes of respiratory depression, hypotension, or nausea and vomiting
      occurred in the fentanyl/propofol group. These results show that
      fentanyl/propofol was superior to other medications used during this study period
      for pediatric sedation with analgesia. Prospective comparison of this medication
      combination with other short-acting agents in patients undergoing both elective
      and emergency procedures is necessary.

PMID- 9928686
TI  - Hypoglycemia in multiple trauma victims.
AB  - The typical presentation of hypoglycemia involves a diaphoretic patient with a
      history of diabetes mellitus who is found with an altered mental status. The
      hypoglycemic patient's presentation may lead the physician to believe that the
      altered mentation may have been caused by some other condition. Hypoglycemia
      occurs rarely in the traumatic setting, yet is easily and rapidly diagnosed with
      bedside testing. A retrospective review was conducted in a university hospital
      emergency department (ED) (level 1 trauma center) of adult trauma patients with a
      Glasgow Coma Scale (GCS) score of <15 who had presented from July 1995 through
      August 1996. Hypoglycemia was defined as a serum glucose level of <60 mg/dL. A
      total of 926 patients (49% of all trauma cases encountered in the period) met
      entry criteria. Four (0.4%) cases of hypoglycemia were encountered in 1
      nondiabetic and 3 diabetic patients; no patient had medical alert warnings. Rapid
      bedside screening identified 2 cases within a mean of 7 minutes after arrival; 1
      patient had an improvement in mental status after dextrose therapy. Two cases
      were identified by formal laboratory analysis a mean of 35 minutes after ED
      arrival; dextrose therapy improved the mental status in 1 patient. These results
      show that hypoglycemia, rare in trauma patients with abnormal GCS scores, may
      mimic significant traumatic injury with mental status alterations. Physicians
      should consider such a diagnosis in patients with an abnormal GCS score and known
      risk situations for hypoglycemia, including diabetes mellitus and chronic alcohol
      use; in such cases, appropriate bedside screening should be performed after
      initial stabilization.

PMID- 9928687
TI  - Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute
      renal colic.
AB  - To compare the efficacy of intramuscular ketorolac and meperidine in the
      emergency department (ED) treatment of renal colic, a prospective, controlled,
      randomized, double-blind trial was conducted in an academic ED with 76,000 annual
      visits. Participants were volunteer ED patients with a diagnosis of
      ureterolithiasis confirmed by intravenous pyelogram. Subjects were randomized 1:1
      to receive a single intramuscular injection of either 60 mg ketorolac or 100 to
      150 mg meperidine, based on weight. Of the 70 patients completing the trial, 33
      received ketorolac and 37 received meperidine. Demographic characteristics and
      baseline pain scores of both groups were comparable (P = NS, Mann Whitney U).
      Ketorolac was significantly (P < .05) more effective than meperidine in reducing
      renal colic at 40, 60, and 90 minutes as measured on a 10-cm visual analogue
      scale. Similar proportions of patients in each group were given rescue analgesia
      and admitted. Of patients who were discharged home without rescue, those treated
      with ketorolac left the ED significantly earlier than those treated with
      meperidine (3.46 v 4.33 h, P < .05). These results show that intramuscular
      ketorolac as a single agent for renal colic is more effective than meperidine and
      promotes earlier discharge of renal colic patients from the ED.

PMID- 9928688
TI  - Dalteparin in emergency patients to prevent admission prior to investigation for
      venous thromboembolism.
AB  - A 15-month prospective cohort study of emergency department (ED) patients with
      suspected venous thromboembolism was conducted to assess the role of low
      molecular weight heparin (dalteparin) in an emergency setting in suspected venous
      thromboembolism prior to diagnostic confirmation. Patients were given a
      therapeutic dose of dalteparin and were discharged home; they then returned the
      next day for diagnostic testing. All patients were followed for 3 months. Of 128
      patients, 44 had positive test results and 84 had negative test results. Four
      patients required admission for other reasons. Seventeen had continuing symptoms
      after initial negative testing; 10 returned to the ED and 9 had repeat Doppler
      ultrasound, all of which remained negative. None of the 84 negative patients were
      diagnosed with venous thromboembolism subsequent to an initial negative test.
      There were no serious adverse effects. This study suggests that treatment with
      low molecular weight heparin pending outpatient investigation for suspected
      venous thromboembolism in emergency patients is safe and effective. This could
      lead to substantial cost savings in the management of this problem. Further study
      is warranted.

PMID- 9928689
TI  - Superoxide production of neutrophils after severe injury: impact of subsequent
      surgery and sepsis.
AB  - To evaluate the early variations of superoxide production of neutrophils (SPN) in
      injured patients, SPN was serially measured on the first, third, and seventh day
      after severe injury (injury severity score of >16). For patients receiving
      subsequent surgery, SPN was measured again on the first postoperative day.
      Eighteen patients were studied. Six had subsequent surgery within 1 day (early
      operation); 6 had surgery 3 days after injury (late operation); 6 did not have
      surgery (nonoperation). SPN increased on the first day and recovered from the
      third day after injury in all three groups. In patients who had surgery, SPN did
      not significantly increase on the first postoperative day. Eight patients
      developed sepsis, 4 of whom had early multiple organ dysfunction (EMOD). On the
      last measurement, mean SPN was suppressed in septic patients with EMOD, whereas
      it was elevated in septic patients without EMOD. Patients with EMOD also had a
      higher injury severity score. In conclusion, subsequent surgery after injury has
      no effect on the priming of neutrophils. While late priming of neutrophils in
      injured patients coincides with the development of sepsis, suppression of SPN is
      found in septic patients with EMOD that frequently results from severe injury.

PMID- 9928691
TI  - Impact of emergency medicine resident training in ultrasonography on ultrasound
      utilization.
AB  - Training programs in bedside ultrasound for emergency physicians often encounter
      considerable resistance, partly because of concern that the number of radiology
      interpreted studies ordered from the ED may decrease. This study attempted to
      determine the effect of instituting an ED training program in ultrasound on the
      ordering of formal studies from a department of radiology. This retrospective,
      computer-assisted review compared all abdominal sonograms ordered from the ED of
      a busy community hospital in the 3 years before introduction of an ultrasound
      training program (1992 through 1994) with those ordered in the 2 years after the
      program's inception (1995, 1996). The number of formal studies significantly
      increased after institution of the training program, both in terms of absolute
      numbers (annual mean 181 v 95, P < .001) and as a percentage of all outpatient
      sonograms ordered at the institution (9.8% v 5.1%, P < .001). Introduction of a
      teaching program in emergency ultrasound appears to increase utilization of
      formal ultrasound services, at least during the training period.

PMID- 9928690
TI  - Provision for clinic patients in the ED produces more nonemergency visits.
AB  - This study sought to evaluate how the addition of a general practitioner (GP)
      surgery influences the utilization of an emergency department (ED). An
      intervention trial with historical control was conducted in a Swedish university
      hospital ED. A GP surgery was established in the ED by the addition of GP
      physicians without the addition of other personnel (nurses, secretaries, aids).
      The number of persons evaluated and managed by the GP physicians and ED
      physicians were quantified preintervention (April 1992 to October 1993) and
      postintervention (April 1994 to October 1995). Further information was obtained
      by questionnaires distributed to all physicians and patients during three sample
      study weeks: 1 week before intervention and 6 and 18 months after the
      intervention. Patient volume, percentages of inappropriate visits, and types of
      services were recorded. The addition of GP physicians increased the number of
      visits to the ED by 27% (4,694 per month to 5,952 per month). The percentage of
      patients managed in the ED who had nonurgent complaints (primary health care
      needs) increased with the intervention from 22% (95% confidence interval [CI]
      19%, 25%) to 33% (95% CI 30%, 37%). The increased demand on the ED of patients
      with nonurgent complaints increased the average waiting time for patients with
      urgent or emergent complaints from 35 minutes to 40 minutes (14%). The
      introduction of GPs to an ED increased the number and proportion of patients
      presenting to the ED with nonurgent complaints.

PMID- 9928692
TI  - The 1996 New York blizzard: impact on noninjury emergency visits.
AB  - The purpose of this study was to investigate the impact of the January 1996 New
      York blizzard on emergency visits to 12 Suffolk County hospitals for 10 noninjury
      health conditions. Emergency charts from the blizzard week (January 7-11) and a
      nonblizzard week (January 21-25) were reviewed and information was abstracted
      from the records meeting the criteria. Blizzard conditions were associated with
      increased visits for myocardial infarction/angina, primarily shoveling-related,
      and with decreased visits for asthma. Diagnoses for the other noninjury
      conditions did not differ significantly between time periods. The decrease in
      asthma visits possibly resulted from asthmatics avoiding exposure to blizzard
      conditions. An unexpected finding was that most patients with shoveling-related
      myocardial infarction/angina did not report pre-existing heart disease. Also of
      interest was that one quarter of myocardial infarction/angina visits by women
      were reportedly shoveling-related. This suggests that health warnings may be less
      effective at decreasing shoveling-induced myocardial infarction if they are
      directed primarily at men and at people with heart disease.

PMID- 9928693
TI  - Diagnostic aids in the differentiation of pyloric stenosis from severe
      gastroesophageal reflux during early infancy: the utility of serum bicarbonate
      and serum chloride.
AB  - This study evaluated whether serum bicarbonate levels, serum chloride levels, and
      other diagnostic criteria could be used to differentiate pyloric stenosis (PS)
      from severe gastroesophageal reflux (GER) during early infancy. The investigation
      was a retrospective, case-control study conducted in the emergency department of
      a large, academic children's hospital. Cases were 75 consecutive infants with PS
      confirmed in the operating room. Controls were 75 consecutive infants 12 weeks of
      age or younger with the diagnosis of GER whose serum electrolytes had been
      examined. Projectile vomiting was sensitive (0.93) but not specific (0.39) for
      PS. The mean serum bicarbonate level was 27.2 mmol/L for PS patients and 22.3
      mmol/L for GER patients (P < .00001), and the mean serum chloride level was 95.7
      mmol/L and 103.6 mmol/L for PS patients and GER patients, respectively (P <
      .00001). Serum bicarbonate levels of > or =29 mmol/L and serum chloride levels of
      < or =98 mmol/L had high positive predictive values (0.96 and 0.97, respectively)
      and were specific (0.99 for both) but not very sensitive (0.36 and 0.50,
      respectively) in identifying patients with PS. Only one patient would have been
      misclassified (false positive) as having PS using either of these cutoff values.
      These laboratory tests can also help discriminate between PS and GER when the
      history and physical examination fail to do so. For example, of the 20 patients
      with PS who did not have a pyloric mass palpated, 3 (15%) had serum bicarbonate
      levels of > or =29 mmol/L, and 6 (30%) had serum chloride levels of < or =98
      mmol/L. In conclusion, the serum bicarbonate or serum chloride level offers a
      useful additional diagnostic tool in the evaluation of children presenting during
      early infancy with vomiting of uncertain etiology.

PMID- 9928694
TI  - Childhood sledding injuries.
AB  - Sledding is only rarely thought of as a potentially dangerous childhood activity.
      However, serious injuries and occasional deaths do occur. A review of patients 18
      years old and younger admitted to a pediatric trauma center following a sledding
      accident from 1991 to 1997 was conducted. By design this study was expected to
      identify the most seriously injured patients. Twenty-five patients were
      identified, all but four younger than 13. Seventeen were boys. The mechanisms of
      injury were: collision with stationary object, 15; sled-sled collision, 1; struck
      by sled, 2; going off jump, 3; foot caught under sled or on ground, 3; fall off
      sled being towed by snowmobile, 1. The average pediatric trauma score was 10.5,
      and the average injury severity score 10.6. There were no deaths. The injuries
      were: head, 11; long bone/extremity, all lower, 10; abdomen, 5; chest, 1; facial,
      2; spinal, 1. Five patients sustained multiple injuries. A surprisingly high
      number, 5, had pre-existing neurological conditions that could have played a
      contributory role in the accident. Sledding is predominantly an activity of
      children, and occasional serious injuries occur. Most are preventable. Obeying
      the simple caveat that sledding should only be done in clear areas away from
      stationary objects would eliminate the great majority of serious injuries.

PMID- 9928695
TI  - Congenital diaphragmatic hernia with gastric volvulus presenting as an acute
      tension gastrothorax.
AB  - This report describes a 3-month-old infant with acute severe respiratory distress
      in whom a diagnosis of congenital diaphragmatic hernia with tension gastrothorax
      and gastric volvulus was made. A review of the pathophysiology, clinical
      presentation, differential diagnosis, diagnostic evaluation, and treatment of
      congenital diaphragmatic hernia is presented.

PMID- 9928696
TI  - Hanging-induced status epilepticus.
AB  - Survival from hanging is associated with a variety of neuropsychiatric
      consequences, including amnesia, localized muscle spasms, transient hemiplegia,
      central cord syndrome, and multiple transient neurologic findings. This report
      describes a near-hanging episode in a patient who subsequently had status
      epilepticus requiring 40 mg of diazepam and 1,200 mg of phenytoin for control in
      the prehospital and emergency department stabilization period. This is the first
      well-documented report of hanging with subsequent status epilepticus in an adult.
      The patient survived with an abnormal electroencephalogram consistent with anoxic
      injury and was discharged on anticonvulsant therapy, although the rationale for
      medication in such patients is unclear and requires further study.

PMID- 9928697
TI  - Impact of medical student preceptorship on ED patient throughput time.
AB  - A prospective, consecutive study was performed to determine if medical student
      supervision in the emergency department (ED) changes patient throughput time (ie,
      the time from triage to discharge). The mean patient throughput time on days when
      medical students were present in the ED (group 1) was compared to the mean
      patient throughput time on days when medical students were absent from the ED
      (group 2). Throughput time was measured in minutes. The mean throughput times of
      the two groups were compared by the two tailed t test (P < .05). The study had a
      power of 90% (beta = .10) to detect a throughput time difference of 20 minutes.
      The two groups were also compared for mean daily acuity (as gauged by mean daily
      number of patient admissions) and mean daily patient census. The differences in
      mean daily throughput times (group 1, 145.2 min v group II, 150.6 min; P = .40),
      mean daily census (group 1, 28.1 patients v group 2, 28.1 patients; P = .75), and
      mean daily admissions (group 1, 10.4 patients v group 2, 10.7 patients; P = .74)
      were all insignificant. Precepting medical students in this ED did not
      significantly change patient throughput times.

PMID- 9928698
TI  - Acute urinary retention due to ectopic pregnancy.
AB  - Two cases of ectopic pregnancy are presented in which acute urinary retention was
      a salient clinical feature. The emergency physician must consider ectopic
      pregnancy in the differential diagnosis in any woman of child-bearing age with
      abdominal, pelvic, or urinary complaints.

PMID- 9928699
TI  - Acute suppurative parotitis with spread to the deep neck spaces.
AB  - This report describes the case of an elderly, diabetic woman who became
      dehydrated and developed acute suppurative parotitis, which caused marked
      swelling of her left face and neck. The parotid infection also extended by
      continuity into the lateral pharyngeal space and contiguous deep neck spaces,
      causing airway-threatening, extensive inflammation and swelling of the epiglottis
      and parapharyngeal soft tissues. The differential diagnosis and diagnostic
      rationale is discussed. The anatomy of the stylomandibular area is reviewed to
      explain how infection of the parotid can spread to the pharynx.

PMID- 9928701
TI  - Sharps disposal in the ED: simple techniques and equipment.
AB  - Disposal of sharp instruments and needles ("sharps") is an ongoing problem in the
      emergency department (ED). Cleanup and disposal of needles and other sharps after
      a procedure is the responsibility of all ED personnel, including physicians.
      Simple cleanup techniques are explained and illustrated. All techniques are
      designed to be done (1) without exposing physician to a needle stick, (2) with
      equipment readily available in the ED, and (3) with containers readily seen by
      those disposing of the sharps and other materials. Adherence to these cleanup
      procedures should help lessen the problem of sharps and disease exposure in the
      ED.

PMID- 9928700
TI  - Hospital evacuations due to hazardous materials incidents.
AB  - In a previous study 12 Washington State hospitals reported evacuations due to
      hazardous materials incidents. A telephone survey was conducted to further
      describe these incidents. Ten hospitals responded to the survey, including one
      institution reporting two incidents. The incidents included threatened explosions
      or releases in three cases and actual chemical exposures in eight cases. The
      actual exposures included irritant gases from mixtures of cleaners in two cases,
      an unknown exposure in one case, and a variety of other chemicals or products in
      the remaining cases. Seven of the 11 incidents resulted in emergency department
      (ED) evacuation. Two incidents involved secondary contamination of ED staff from
      treatment of patients with chemical exposures who were not decontaminated prior
      to arrival. Fire department personnel assisted in the majority of incidents.
      Review of these cases provides useful information for planning drills to test
      emergency preparedness as required under Joint Commission on Accreditation of
      Healthcare Organizations standards.

PMID- 9928702
TI  - Database model for patients admitted to a chest pain center.

PMID- 9928703
TI  - Pulse oximetry: principles and limitations.
AB  - The pulse oximeter has become an essential tool in the modern practice of
      emergency medicine. However, despite the reliance placed on the information this
      monitor offers, the underlying principles and associated limitations of pulse
      oximetry are poorly understood by medical practitioners. This article reviews the
      principles of pulse oximetry, with an eye toward recognizing the limitations of
      this tool. Among these are performance limitations in the settings of
      carboxyhemoglobinemia, methemoglobinemia, motion artifact, hypotension,
      vasoconstriction, and anemia. The accuracy of pulse oximetry is discussed in
      light of these factors, with further discussion of applications for pulse
      oximetry in emergency medicine, including both oximetric and plethysmographic
      operation. The pulse oximeter is an invaluable instrument for emergency medicine
      practice, but as with any test the data it offers must be critically appraised
      for proper interpretation and utilization.

PMID- 9928704
TI  - The changing presentation of pyloric stenosis.
AB  - Metabolic abnormalities described in pyloric stenosis are now rare, probably
      because of prompter recognition of the disease. This report reviews the trend in
      presentation over three decades. All infants treated for pyloric stenosis during
      three mid-decade target periods were reviewed. Comparison between the 1975 group
      and the 1985 group and between the 1995 group and previous decades were designed
      to identify the impact of ultrasonography, since this modality has only been
      available in the last decade. Parameters included age at diagnosis and incidence
      of water and electrolyte imbalance as measures of delay in presentation. Two
      hundred eighty-three patients were reviewed. Mean age (weeks) at presentation was
      5.4+/-3.0 in 1975, 4.6+/-2.0 in 1985, and 3.4+/-1.3 in 1995 (P < .05, ANOVA).
      Overall, 88% had no electrolyte anomalies on admission. There was no statistical
      difference in frequency of abnormal results between the three decades. Total and
      postoperative hospitalization was significantly shorter in the recent period: in
      1985, 5.34 and 4.36 days; in 1985, 4.48 and 3.4 days; and in 1995, 3.8 and 2.8
      days. These data show that pyloric stenosis is now recognized earlier than in
      previous decades. The availability of ultrasonography cannot solely be credited
      for earlier diagnosis, since this trend was already apparent before its
      introduction. The "classic" metabolic derangements associated with pyloric
      stenosis have been highly uncommon for the past three decades.

PMID- 9928705
TI  - Usefulness of the blood urea nitrogen/creatinine ratio in gastrointestinal
      bleeding.
AB  - This study was conducted to evaluate the blood urea nitrogen/creatinine (BUN/Cr)
      ratio for distinguishing an upper versus lower source of gastrointestinal (GI)
      bleeding. Charts of patients who presented to the emergency department (ED) with
      the diagnosis of GI bleeding from August 1995 to August 1996 were retrospectively
      reviewed for source of bleeding, initial BUN, Cr, BUN/Cr ratio, hematocrit (Hct),
      and need for transfusion. A total of 124 patients were eligible for inclusion, 71
      (57%) of whom were male. A total of 63 (51%) presented with blood in stool and 53
      (43%) with bloody emesis; 8 (6%) had blood in both emesis and stool. A total of
      31 (25%) patients had a lower GI bleed, 88 (70%) had an upper, and 5 (4%) had
      both upper and lower bleeding sources. The mean BUN level was 24 mg/dL, the mean
      Cr level 1.03 mg/dL, and the mean BUN/Cr ratio was 24. The mean hemoglobin (Hb)
      level was 11.3 g/dL, the mean Hct was 32 g/dL, and 51% required transfusion.
      Upper GI bleeding was significantly correlated with age younger than 50 (P = .01)
      and male gender (P = .01; odds ratio, 3.13). Taking into account age and gender,
      the BUN/Cr ratio correlated significantly with an upper GI source of bleeding (P
      = .03), with a ratio greater than 36 having a sensitivity of 90% and a
      specificity of 27%. The area under the receiver operating characteristic curve
      using age, gender, and BUN/Cr ratio was .73 (95% confidence interval, .62 to
      .84).

PMID- 9928706
TI  - Displaced odontoid fracture in a 9-month-old child.
AB  - A 9-month-old child sustained a displaced odontoid fracture in a motor vehicle
      accident. She was treated with closed reduction and a Minerva cast for 6 weeks,
      followed by a collar for an additional 2 weeks. At 5-year follow-up, she had made
      a complete recovery with solid union, no deformity, and no instability.

PMID- 9928707
TI  - Intercondylar dislocation of the patella with vertical axis rotation.
AB  - A rare case is presented of intercondylar dislocation of the patella with
      vertical axis rotation. The injury was the result of blunt trauma directed to the
      lateral border of the patella. The patient presented with the knee locked in full
      extension and with a vertical ridge-shaped deformity caused by the medial border
      of the patella facing anteriorly. Reduction was accomplished under intravenous
      conscious sedation by manipulation.

PMID- 9928708
TI  - Unusual wrist pain: pisiform dislocation and fracture.
AB  - Injuries to the wrist can be challenging to the emergency physician. Injuries to
      the pisiform bone are rare entities, and their diagnosis may be delayed,
      increasing the morbidity to the patient. The report describes the cases of a 62
      year-old woman with a pisiform dislocation and a 35-year-old man with a pisiform
      fracture. Excision of the pisiform bone was required in both cases, and both
      patients had good clinical response.

PMID- 9928709
TI  - Torsades de pointes: a case with multiple variables.
AB  - Torsades de pointes is a polymorphic ventricular tachycardia that displays a
      unique electrocardiographic feature of twisting of the mean electrical axis of
      QRS complexes around an isoelectric line on the surface electrocardiogram. It is
      associated with long QT syndrome and has many precipitating mechanisms, etiologic
      factors, and treatment options. This report presents a case of torsades de
      pointes that was precipitated by multiple factors and required many treatment
      modalities. The patient in this case exhibited features of both congenital and
      acquired types of long QT syndrome.

PMID- 9928710
TI  - Lung cancer mimicking acute myocardial infarction on electrocardiogram.
AB  - Myocardial involvement by malignant neoplasm is rare and often not clinically
      manifested. The diagnosis is usually made only at autopsy. A 71-year-old man with
      squamous cell lung cancer presented with chest discomfort. His electrocardiogram
      was diagnostic of acute myocardial infarction. However, because of the lack of
      classic symptoms and signs of acute myocardial infarction and normal serum levels
      of cardiac enzymes, an echocardiography was performed before initiation of
      thrombolytic therapy. The echocardiography showed a huge hyperechoic mass located
      in the posterolateral aspect of the left ventricle with myocardium invasion.
      Thrombolytic therapy was withheld. In patients with lung cancer, an
      electrocardiogram representative of acute myocardial infarction can rarely be
      induced by myocardial involvement with lung cancer.

PMID- 9928711
TI  - Cases in electrocardiography.

PMID- 9928713
TI  - Elderly use of the ED in an Asian metropolis.
AB  - To compare emergency department (ED) use by elderly patients (age 65 yrs or
      older) with that by younger adult patients (age 15-64 yrs), a prospective
      consecutive chart review study was conducted from August 1, 1995 through May 31,
      1996 in eight designated hospitals in Taipei city (which has 2.6 million
      residents, 8.4% of whom are 65 yrs or older). Patient age, sex, mode of arrival,
      living status, triage category, advanced life support (ALS) eligibility,
      referral, confinement to bed, intensive care unit (ICU) admission, impression,
      trauma mechanism, and disposition were recorded and compared between the two
      groups. Of 27,765 adult emergency patients studied during the 10 months, 24% were
      elderly. The elderly were more likely to be ambulance cases, of high acuity and
      ALS eligibility, living alone, bed-ridden, and ICU cases (19.4% v 10.5%, 14.8% v
      5.5%, 14.7% v 4.3%, 9.7% v 4.1%, 16% v 1.1%, and 4.0 v 1.1%, respectively). The
      three leading illnesses in the elderly were cerebral vascular accident (6.6%),
      cancer (5.6%), and cardiovascular disease (5.6%), and the two most common trauma
      mechanisms were trip (fall from the same level surface) (57.2%) and traffic
      accident (20.7%). Twenty-seven percent and 22.7% of elderly were disposed to
      admission and observation, respectively, compared with the 10.9% and 11.4% of the
      younger patients. Elderly patients have significantly different and more severe
      presentations to the ED compared with younger adults.

PMID- 9928712
TI  - Use of subcutaneous terbutaline to reverse peripheral ischemia.
AB  - Four cases are presented, one involving extravasation of a dopamine and
      dobutamine solution in the arm and three involving accidental digital injection
      of epinephrine into the thumb. In three cases, local infiltration of terbutaline
      resulted in dramatic reversal of vasospasm and ischemia. In the remaining case
      the use of terbutaline resulted in minor clinical improvement. These are the
      first reported cases involving the successful treatment of peripheral ischemia
      with subcutaneous terbutaline. This experience suggests that terbutaline may be
      an effective alternative for treatment of peripheral ischemia when phentolamine
      is not available.

PMID- 9928714
TI  - Pediatric emergency medicine fellowship training: a survey of program directors.

PMID- 9928715
TI  - Ruptured retroperitoneal aneurysm in a patient taking phentermine hydrochloride.

PMID- 9928716
TI  - Elbow dislocation complicated by brachial artery laceration.

PMID- 9928718
TI  - Thrombolytic therapy and prophylactic anticoagulation in pregnant patients.

PMID- 9928717
TI  - Ophthalmoplegia: an unusual manifestation of hypocalcemia.

PMID- 9928719
TI  - Seizures in a diabetic patient on monoamine oxidase inhibitors.

PMID- 9928720
TI  - Upper airway burn from crack cocaine pipe screen ingestion.

PMID- 9928721
TI  - Droperidol for the treatment of acute peripheral vertigo.

PMID- 9928722
TI  - Acceptance and publication times in the four major emergency medicine journals.

PMID- 9928723
TI  - Comparison of HTLV-I basal transcription and expression of CREB/ATF-1/CREM family
      members in peripheral blood mononuclear cells and Jurkat T cells.
AB  - HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma and is associated
      with tropical spastic paraparesis/HTLV-I-associated myelopathy. Following
      integration into the host cell genome, HTLV-I replication is regulated by both
      host and viral mechanisms that control transcription. Low levels of viral
      transcription (basal transcription) occur before expression of the virally
      encoded Tax protein (Tax-mediated transcription). Members of the cyclic adenosine
      monophosphate (cAMP) response element binding (CREB)/activating transcription
      factor 1 (ATF-1) family of transcription factors bind three 21-bp repeats (Tax
      responsive element-1, or TRE-1) within the viral promoter and are important for
      basal and Tax-mediated transcription. Using mitogen stimulated and quiescent
      peripheral blood mononuclear cells (PBMC) and Jurkat cells, we compared
      differences in basal transcription and amounts and binding of transcription
      factors with TRE-1. We demonstrate that amounts of transcriptionally active
      phosphorylated CREB protein (P-CREB) differ between activated PBMC and Jurkat
      cells. Following stimulation, P-CREB levels remain elevated in PBMC for up to 24
      hours whereas CREB is dephosphorylated in Jurkat cells within 4 hours following
      stimulation. The differences in P-CREB levels between PBMC and Jurkat cells were
      directly correlated with basal transcription of HTLV-I in the two cell types.
      Using electrophoretic mobility shift assays, we determined that the pattern of
      band migration differed between the two cell types. These data demonstrate that
      PBMC differentially regulate basal HTLV-I transcription compared with Jurkat T
      cells, and this differential regulation is due, in part to differential
      phosphorylation and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter. We
      demonstrate the utility of using primary lymphocyte models to study HTLV-I
      transcription in the context of cell signaling and suggest that activated PBMC
      maintain elevated levels of P-CREB, which promote basal HTLV-I transcription and
      enhance viral persistence in vivo.

PMID- 9928724
TI  - A randomized, double-blind trial on the use of a triple combination including
      nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in
      antiretroviral-naive patients with advanced disease.
AB  - The immunologic and virologic activity of nevirapine in combination with two
      nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in
      antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all,
      68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A
      group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received
      ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on
      peripheral blood CD4+ cells, with differences between groups analyzed by the
      Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment
      groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were
      significantly higher with the triple combination (median RNA reductions, 2.69
      versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4
      increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48
      weeks). This study demonstrates that a triple combination of ZDV + ddI +
      nevirapine used as first-line regimen in antiretroviral-naive patients can induce
      sustained virologic and immunologic response in patients with low CD4 count or a
      previous diagnosis of AIDS.

PMID- 9928725
TI  - Concomitant therapy with subcutaneous interleukin-2 and zidovudine plus
      didanosine in patients with early stage HIV infection.
AB  - A phase II study was performed to evaluate the feasibility and activity of
      subcutaneous (SC) interleukin-2 (IL-2) administration plus zidovudine (ZDV) and
      didanosine (ddI) in patients with early stage HIV infection. Between October 1995
      and October 1996, 12 patients completed 6 cycles of the following scheduled
      therapy: ZDV plus ddI and SC self-administration of 6 mIU of IL-2 at days 1 to 5
      and 8 to 12 of a 28-day cycle for a total of 6 cycles (24 weeks). After 6 cycles,
      patients received only ZDV plus ddI and they were observed up for an additional
      24 weeks. Our schedule was well tolerated as an outpatient regimen and led to a
      significant elevation in CD4 count, which lasted for 24 weeks after the end of IL
      2 therapy. Moreover, CD4/CD25, as well as CD4/CD45RO and CD4/CD45RA, cell levels
      were significantly increased at the end of the therapy and remained significantly
      elevated after 24 weeks. During the 6 cycles, HIV-associated viremia was
      significantly decreased and, accordingly, we observed a significant decline of
      proviral DNA in peripheral blood mononuclear cells (PBMCs). During follow-up, 10
      of 12 treated patients continued to show levels of HIV-related viremia <500
      copies/ml. Our results demonstrated that IL-2 and ZDV plus ddI is a well
      tolerated and effective therapy for patients with HIV in early stages of the
      disease.

PMID- 9928726
TI  - Protease inhibitor-based therapy is associated with decreased HIV-related health
      care costs in men treated at a Veterans Administration hospital.
AB  - BACKGROUND: Protease inhibitor (PI) therapy for HIV infection is associated with
      decreased rates of opportunistic infections and death. Statistical models predict
      that decreased complications will be associated with decreased hospitalization
      costs. A recent report suggested that the decrease in the HIV hospitalization
      costs were offset by increases in demand for outpatient services. We performed a
      study of hospital use and HIV-associated health care costs in our center to
      determine the following: whether PI therapy is associated with decreased
      inpatient use; whether PI therapy is associated with decreased outpatient use and
      costs; whether decreased HIV health care costs are associated with increased use
      of nucleoside analogues. METHODS: The Dallas Veteran Affairs Medical Center
      provides comprehensive inpatient and outpatient HIV care and thus can evaluate
      the relation between inpatient and outpatient costs. The mean monthly number of
      hospital days, Infectious Diseases clinic visits, emergency department visits,
      other outpatient clinic visits, inpatient costs, outpatient costs, and PI costs
      were determined from January 1, 1995 through July 31, 1997. This time period was
      then divided into three intervals. Comparisons of PI use and HIV-related health
      care costs were during the three intervals was performed using analysis of
      variance (ANOVA). Significant differences between the baseline characteristics
      were further analyzed through multiple linear regression. RESULTS: A decrease in
      hospital days, and all outpatient visits including emergency visits, and HIV
      clinic visits was determined. No difference was found in the rate of use of other
      outpatient services. The per patient costs of HIV care decreased from a monthly
      average of $1905 U.S. in the first interval to $1122 U.S. in the last interval (p
      < .01). Linear regression demonstrated an inverse relation between PI use and
      total HIV costs (B=-0.67, p=.00, adjusted R2=0.52) but no relation between
      nucleoside use, stage of disease or financial class. CONCLUSIONS: PI therapy is
      associated with decreased hospital days and use of outpatient services. Total
      patient costs decreased, but a concomitant rise in outpatient costs took place.
      This increase was primarily a result of increased costs of acquiring PI.
      Increases in the number of nucleoside agents prescribed were not associated with
      decreased costs.

PMID- 9928727
TI  - Effect of antiviral drugs used to treat cytomegalovirus end-organ disease on
      subsequent course of previously diagnosed Kaposi's sarcoma in patients with AIDS.
AB  - OBJECTIVE: To evaluate the association of ganciclovir (GCV) and foscarnet (PFA)
      therapy with the outcome of previously diagnosed Kaposi's sarcoma (KS) after
      initiating antiviral therapy for cytomegalovirus (CMV) end-organ disease. DESIGN:
      Retrospective study. METHODS: KS progression was defined as a clinically obvious
      increase in size of baseline cutaneous or mucosal lesions, a new diagnosis of
      visceral KS, or initiation of a new systemic antineoplastic regimen or radiation
      therapy to treat KS. Multivariate analyses of risk of KS progression were
      calculated for prior duration of KS before initiating CMV treatment, treatment
      with PFA or GCV, number of weeks treated with PFA or GCV, absolute CD4 lymphocyte
      count at time of CMV-related disease diagnosis, diagnosis of KS prior to 1991,
      visceral KS, prior systemic chemotherapy, and prior radiation therapy. RESULTS:
      Among 66 patients who received > or = 14 days PFA (N=20) or only GCV (N=46),
      median time to progression of KS was 211 days (95% confidence interval [CI], 46
      578) for patients who received PFA versus 22 days (95% CI, 15-41) for those who
      received only GCV (p < .001). In the stepwise multivariate analysis, only prior
      visceral KS (rate ratio [RR]=2.80; 95% CI, 1.07-7.35) and foscarnet therapy (RR =
      0.24; 95% CI, 0.11-0.53) were significantly associated with risk of KS
      progression. CONCLUSION: PFA may be an effective therapy for AIDS-related KS;
      prospective trials are indicated.

PMID- 9928728
TI  - Failure to detect nelfinavir in the cerebrospinal fluid of HIV-1--infected
      patients with and without AIDS dementia complex.
AB  - OBJECTIVE: To assess the penetration of the HIV-1 protease inhibitor, nelfinavir,
      into cerebrospinal fluid (CSF). DESIGN: Nelfinavir, a commonly used HIV-1
      protease inhibitor (PI), is highly effective for reducing plasma viral load. It
      is deployed clinically in combination with other antiretroviral agents, including
      nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs).
      Despite its potency based on plasma HIV-1 RNA results, its effectiveness in
      reducing HIV-1 RNA levels (i.e., viral load) in the central nervous system (CNS)
      is less certain. We sampled the CSF as a surrogate for brain because this fluid
      also is separated from the blood by a barrier to free diffusion, the blood-CSF
      barrier (BCB), which shares properties with the blood-brain barrier (BBB). These
      studies of nelfinavir CSF pharmacokinetics exploited the multiple CSF samples
      derived from individual study subjects who were enrolled in studies the primary
      objective of which was to compare viral kinetics in CSF and blood in response to
      antiviral therapy. METHODS: Six study subjects, four with and two without AIDS
      dementia complex, underwent multiple lumbar punctures (LP). Intervals of CSF
      sampling after drug dosing were varied (from 0.48 hours to 10.3 hours after
      nelfinavir administration) to quantitate nelfinavir concentrations throughout the
      steady-state dosing interval. In four study subjects, CSF sampling was
      accompanied by assessment of nelfinavir levels in plasma before and after LP,
      whereas in the other two subjects, a single plasma sample was obtained before or
      after the LP. In total, 25 CSF samples were analyzed. Nelfinavir concentrations
      in CSF and plasma were determined using an high-performance liquid chromatography
      (HPLC) method with a limit of quantitation of 25 and 50 ng/ml, respectively.
      RESULTS: Plasma concentrations before and after LP averaged 2420+/-1365 ng/ml and
      2528+/-1132 ng/ml, respectively. Nelfinavir was not detected in any of the CSF
      samples and levels >25 ng/ml were not present in the CSF. Thus, standard therapy
      with nelfinavir does not result in CSF drug concentrations at or exceeding the
      IC95 level for most HIV-1 isolates. However, study subjects with high CSF viral
      loads experienced a marked reduction in the context of the combination-drug
      regimen including nelfinavir with two subjects showing a comparable CSF response
      with that in plasma. CONCLUSIONS: Nelfinavir does not appreciably penetrate into
      the CSF. The clinical importance of this observation is not certain, in that in
      four study subjects who initiated nelfinavir in combination with other
      antiretroviral therapy, a comparable degree of viral suppression was obtained in
      both the CSF and the blood when sampled 4 weeks or later after initiating
      therapy.

PMID- 9928729
TI  - Short-term effects of large-dose vitamin A supplementation on viral load and
      immune response in HIV-infected women.
AB  - Vitamin A supplementation has been suggested for treatment and prevention of HIV
      infection. However, some in vitro data indicate that vitamin A may activate HIV.
      Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive
      a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV
      1 RNA concentration, total lymphocytes, selected lymphocyte subsets and
      activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin
      (PHA) and Candida were measured before dosing and at various time points over an
      8-week follow-up period. No differences were found between treatment groups in
      the frequency of signs or symptoms of acute vitamin A toxicity, nor were
      differences evident in any lymphocyte subset or activation marker at any time
      during follow-up. Mean and median viral load concentration at each time point and
      change in viral load from baseline to each follow-up point did not differ between
      treatment groups. No difference was measured between treatment groups in the
      proportion of women who responded to PHA or Candida. This study provides no
      evidence that high dose vitamin A supplementation of HIV-infected women is
      associated with significant clinical or immunologic adverse effects.

PMID- 9928730
TI  - HIV infection and disturbances of vaginal flora during pregnancy.
AB  - Disturbances of vaginal flora are common among women of reproductive age. In
      areas of sub-Saharan Africa where the prevalence of HIV is high, the frequency of
      bacterial vaginosis (BV) is also high. In this study, we assessed the association
      of BV and other disturbances of vaginal flora with prevalent HIV infection in two
      cross-sectional studies among pregnant women in urban Malawi. The prevalence of
      HIV-1 was 23% in 1990 and 30% in 1993. Overall, 30% of the women had BV, 59% had
      mild or moderate disturbance of vaginal flora, and only 11% had normal vaginal
      flora. Increasing prevalence of HIV was significantly associated with increasing
      severity of disturbance of vaginal flora (p < .00001, chi2 trend test). This
      trend of increased prevalence persisted after controlling for concurrent sexually
      transmitted diseases (STDs), sexual activity, and socioeconomic factors. After
      multivariate adjustment for potential confounders, the odds ratio for the
      association of BV with prevalent HIV infection was 3.0 (95% confidence interval
      [CI], 2.4-3.8), that of moderate vaginal disturbance with HIV infection was 2.2
      (95% CI, 1.7-2.8), and that of mild vaginal disturbance with HIV infection was
      1.6 (95% CI, 1.3-2.1). Among women with BV, HIV infection was higher among
      younger women than older, implying more recent infection. Although these studies
      were cross-sectional, our data suggest that BV could be associated with increased
      susceptibility to HIV infection.

PMID- 9928731
TI  - HIV-1 subtypes among blood donors from Rio de Janeiro, Brazil.
AB  - The prevalence of HIV infection in Brazil is one of the highest in the world. In
      addition, transfusion-transmitted HIV accounts for 2.3% of all AIDS cases in
      Brazil. The objective of this study was to evaluate genetic diversity and
      distribution of HIV-1 strains circulating in the blood-donor population. We
      characterized 43 seropositive blood units collected from volunteer blood donors
      residing throughout Rio de Janeiro, Brazil. Viral RNA was extracted from plasma,
      reverse transcribed, and amplified by nested polymerase chain reaction (PCR)
      using HIV group M degenerate primers. Genetic heterogeneity was evaluated by
      direct automated cycle sequencing of the following gene fragments: gag p24 (399
      bp), env C2V3 (345 bp), and env gp41 (369 bp). Phylogenetic analysis reflected
      the complexity of the Brazilian HIV epidemic: the majority of specimens, 33 of 43
      (76.7%) were subtype B, and 6 of 43 (14%) were subtype F. The remaining 4 samples
      (9.3%) involved potential mosaic viruses of subtypes B and F or B and D. This
      survey is the first to document HIV-1 genetic variation in the Brazilian blood
      donor population.

PMID- 9928732
TI  - Risk behavior and HIV infection among new drug injectors in the era of AIDS in
      New York City.
AB  - OBJECTIVE: To examine HIV risk behavior and HIV infection among new initiates
      into illicit drug injection in New York City. DESIGN AND METHODS: Cross-sectional
      surveys of injecting drug users (IDUs) recruited from a large detoxification
      treatment program (n=2489) and a street store-front research site (n=2630) in New
      York City from 1990 through 1996. Interviews covering demographics, drug use
      history, and HIV risk behavior were administered; serum samples were collected
      for HIV testing. Subjects were categorized into two groups of newer injectors:
      very recent initiates (just began injecting through 3 years) and recent initiates
      (injecting 4-6 years); and long-term injectors (injecting > or = 7 years).
      RESULTS: 954 of 5119 (19%) of the study subjects were newer injectors,
      essentially all of whom had begun injecting after knowledge about AIDS was
      widespread among IDUs in the city. New injectors were more likely to be female
      and white than long-term injectors, and new injectors were more likely to have
      begun injecting at an older age (median age at first injection for very recent
      initiates, 27 years; median age at first injection for recent initiates, 25
      years; compared with median age at first injection for long-term injectors, 17
      years). The newer injectors generally matched the long-term injectors in
      frequencies of HIV risk behavior; no significant differences were found among
      these groups on four measures of injection risk behavior. HIV infection was
      substantial among the newer injectors: HIV prevalence was 11% among the very
      recent initiates and 18% among the recent initiates. Among the new injectors,
      African Americans, Hispanics, females, and men who engaged in male-male sex were
      more likely to be infected. CONCLUSIONS: The new injectors appear to have adopted
      the reduced risk injection practices of long-term injectors in the city. HIV
      infection among new injectors, however, must still be considered a considerable
      public health problem in New York City.

PMID- 9928734
TI  - Distribution of the CCR5 gene 32-base pair deletion in Israeli ethnic groups.
AB  - The discovery of inhibition of HIV-1 by selected chemokines and their receptors
      instills hope in AIDS researchers, especially because a 32-bp deletion in the
      chemokine receptor CCR5 (delta32-CCR5) provides resistance to HIV infection. A
      recent report found that the highest delta32-CCR5 frequency is among Ashkenazi
      Jews (20.93%). In the present study, we have determined by PCR the allelic
      frequency of delta32-CCR5 in 520 individuals representing a spectrum of ethnic
      groups living in Israel. The samples were obtained from the Israeli National
      Laboratory of Genetic Diversity. Our results showed that Ashkenazi Jews, as to be
      expected, have the highest frequency (10.19%), yet not significantly higher than
      that which has been reported for whites of European decent. Other ethnic groups,
      North African Jews, non-Jews, Middle Eastern Jews, and Ethiopian Jews, gave
      allelic frequencies of 2.08, 1.35, 1.15, and 0, respectively. Thus, the delta32
      CCR5 mutation is found in Jews with the same allelic frequency as that found for
      residents of their countries of origin. Therefore, it appears that the delta32
      CCR5 allele has been introduced into Jewish communities world wide through
      intermarriage and genetic drift.

PMID- 9928733
TI  - Survival of HIV-1 in syringes.
AB  - We performed a study to determine the duration of survival of HIV-1 in syringes
      typically used by injectors of illicit drugs (IDUs). We describe the
      effectiveness of a microculture assay in detecting viable virus in volumes of
      blood typical of those commonly found inside used syringes. Using this assay and
      modeling the worse-case situation for syringe sharing, we have recovered viable,
      proliferating HIV-1 from syringes that have been maintained at room temperature
      for periods in excess of 4 weeks. The percentage of syringes with viable virus
      varied with the volume of residual blood and the titer of HIV-1 in the blood.
      These experiments provide a scientific basis for needle exchange schemes, harm
      reduction, and other interventions among IDUs that support the nonsharing and
      removal of used syringes from circulation.

PMID- 9928735
TI  - Effect of race on insurance coverage and health service use for HIV-infected gay
      men.
AB  - OBJECTIVE: To determine whether race is associated with health insurance coverage
      and health service use among gay and bisexual men in the Baltimore center of the
      Multicenter AIDS Cohort Study. METHODS: Data from eight semiannual study visits
      between 1991 and 1996 were used. Descriptive, stratified, and logistic regression
      analyses were conducted to determine whether race is associated with insurance
      coverage, medical, or dental service use, after controlling for socioeconomic
      variables. RESULTS: No difference was found between blacks' and whites'
      likelihood of having health insurance, private insurance, using inpatient,
      emergency department services, or antiretroviral medications. Whites were more
      likely to use outpatient services, particularly if CD4 cell counts were high, and
      were more likely to use dental services, although blacks were more likely to have
      dental insurance. CONCLUSIONS: Further research must be conducted to examine
      cultural, social, and psychological factors that help explain why white gay men
      use more outpatient and dental services, when other service use is unrelated to
      race. Investigators should be precise when using race as a variable in health
      services and epidemiologic research, emphasizing when racial differences truly
      exist versus when the variable race is a surrogate for another factor.

PMID- 9928736
TI  - Further characterization of HIV-1 isolates from Ho Chi Minh City, Vietnam.

PMID- 9928738
TI  - Cytokine profiles in a cohort of long-term survivors of transfusion-acquired HIV
      1 infection.

PMID- 9928737
TI  - Antibodies to the CD4-binding site of HIV-1 gp120 in patients infected by
      variants belonging to the M or O group.

PMID- 9928739
TI  - How frequently should viral load be monitored to evaluate antiretroviral
      therapies in AIDS clinical trials?

PMID- 9928740
TI  - HIV viral loads reach steady state in the United States.

PMID- 9928741
TI  - Failure of pediatric AIDS prevention despite maternal HIV screening in Paris,
      France.

PMID- 9928742
TI  - High prevalence of HTLV-I infection in Argentinian blood donors: a new HTLV-I
      endemic area?

PMID- 9928743
TI  - HTLV-I and HTLV-II coexist among the Embera and Inga Amerindians of Colombia.

PMID- 9928744
TI  - Salt reduction and cardiovascular risk: the anatomy of a myth.

PMID- 9928745
TI  - White coat hypertension: a recognised syndrome with uncertain implications.

PMID- 9928746
TI  - Target organ involvement in hypertensive patients in Eastern Sudan.
AB  - Hypertension has become a major cause of cardiovascular morbidity and mortality
      in both the developed and the developing nations. In a cross-sectional study we
      assessed the state of blood pressure (BP) control and the pattern of target organ
      complications in 198 Sudanese patients treated in a teaching hospital in Kassala
      town in Eastern Sudan, (mean age 53 years, 76% women). Excellent BP control (BP
      <140/90 mm Hg) was achieved in 46% of the patients. Stage 2 or Stage 3 target
      organ involvement, particularly albuminuria and ischaemic heart disease, were
      detected in one-third of the patients. These complications were found to be
      related to both the severity and the duration of hypertension as well as to the
      frequency of cigarette smoking. Factors such as poor compliance, adverse
      socioeconomic status, as well as obesity and cigarette smoking may account for
      poor BP control and hence the development of hypertensive complications. We
      conclude that optimal BP control is not yet achieved in the majority of
      hypertensives in the Sudan. Reasons for this failure should be identified and
      corrected in order to avoid hypertensive target organ damage.

PMID- 9928748
TI  - Blood pressure, hypertension and correlates in urbanised workers in Ibadan,
      Nigeria: a revisit.
AB  - To provide an update on blood pressure (BP) levels and hypertension correlates in
      urban workers in Ibadan, Nigeria, we administered a questionnaire to, and
      measured the BP in, 608 men and 309 women, age range 18-64 years. Systolic BP
      (SBP) rose in men and women after the age of 25, but the rise in diastolic BP
      (DBP) started earlier dropping in women only after the age of 44. SBP and DBP
      were higher in men than women (P < 0.001). The prevalence of hypertension was
      9.3% in the population, being 10.4% in men and 7.1% in women; age-adjusted rates
      were 9.8% and 8.0% respectively. The prevalence of hypertension increased with
      age in both genders. Body mass index was correlated to SBP (r = 0.142, P = 0.022)
      and DBP (r = 0.149, P = 0.032) in men, and with SBP (r = 0.1501, P = 0.013) and
      DBP (r = 0.1569, P = 0.0085) in women. BP was correlated to years of education (P
      < 0.001) and income (P < 0.001) in men, but not in women. Regular and moderate
      alcohol consumption was associated with hypertension (chi2 = 4.8, P < 0.05).
      Awareness of BP status was generally low, 7.7% in men and 8.7% in women, but was
      significantly higher in the hypertensives than the normotensives (chi2 = 241, P <
      0.0001). The hypertension prevalence rates are not too different from figures
      obtained in the last four decades, which generally have not exceeded 15%, inspite
      of the apparent influence of the modernisation indices of education and income.

PMID- 9928747
TI  - Ten-year incidence of elevated blood pressure and its predictors: the CARDIA
      study. Coronary Artery Risk Development in (Young) Adults.
AB  - Few prospective studies have examined associations of lifestyle factors or
      variables in the insulin resistance syndrome (syndrome X) with incidence of
      elevated blood pressure (BP) in black subjects and women. This report estimates
      the 10-year incidence of high blood pressure (HBP) and high normal blood pressure
      (HNBP) in the biracial cohort of the Coronary Artery Risk Development in (Young)
      Adults Study (CARDIA), and examines lifestyle factors and four syndrome X
      variables, measured at baseline, as predictors. CARDIA examined 5115 black and
      white men and women aged 18-30 years in 1985-1986, and re-examined them at 2, 5,
      7, and 10 years. The 10-year incidence of HBP was 16.4% in black men, 7.8% in
      white men, 13.1% in black women, and 3.2% in white women, while the 10-year
      incidence of HBP or HNBP was 29.5%, 16.2%, 19.2%, and 6.3%, respectively, in the
      four sex-race subgroups. Predictors included body mass index, waist
      circumference, physical activity, alcohol intake, pulse rate, cigarette smoking,
      education, fasting insulin, triglycerides, uric acid, and high-density
      lipoprotein cholesterol, as well as age and systolic BP. In univariate analyses,
      each of these variables was significantly related to incidence in at least one of
      the four sex-race groups. In multivariate analyses that included control for age
      and systolic pressure, independent predictors included fasting insulin in white
      men and women, triglycerides in white men, uric acid and pulse rate in black men,
      waist circumference in white men and black women, and education (inverse) in
      white men and black and white women. These results suggest that lower
      socioeconomic status, as assessed by education level, and one or more syndrome X
      variables, ie, fasting insulin, triglycerides, uric acid, may be associated with
      development of elevated BP in young adults.

PMID- 9928749
TI  - Impaired baroreflex function and arterial compliance in primary aldosteronism.
AB  - The purpose of this study was to evaluate if changes in vascular properties were
      related to baroreflex function in patients with primary aldosteronism. Twenty
      three patients with primary aldosteronism, 22 essential hypertensive patients and
      16 normal controls were studied. Continuous finger blood pressure (BP) was
      recorded by Portapres device during supine rest and active stand up. Compliance
      was estimated from the time constant of pressure decay during diastole.
      Baroreflex sensitivity was calculated by autoregressive cross-spectral analysis
      of systolic BP and interbeat interval. The result was that baroreflex gain and
      compliance were lower in primary aldosteronism patients in the supine position (P
      = 0.002 and P < 0.05 respectively). Aldosterone plasma levels (R2 = 0.31, P =
      0.01), age, systolic and diastolic BP, high and low frequency components of
      diastolic BP variability were independently related to compliance in primary
      aldosteronism. In conclusion primary aldosteronism is associated with an impaired
      baroreflex function related in part to a reduced arterial compliance. Despite a
      reduction of BP values and aldosterone levels, surgical or pharmacological
      treatment did not significantly change compliance values.

PMID- 9928750
TI  - Hypertension and renal failure in Kumasi, Ghana.
AB  - Hypertension is common in West Africa and likely to become more common as
      urbanisation increases. There are at present few facilities for the detection and
      management of hypertension so the influence it has on overall morbidity and
      mortality in the population is not clear. The objectives of the study were to
      assess: (a) renal disease and blood pressure related admissions and deaths among
      acute medical admissions to Komfo Anokye Teaching Hospital, Kumasi, during an 8
      month period; and (b) the burden of renal disease among out-patient hypertensives
      at the same hospital. Ward admission books were examined in the four acute
      medical wards to ascertain admission diagnosis and cause of death (two 4-month
      periods in 1995 and 1996). Clinical assessment (blood pressure, plasma
      creatinine, proteinuria) was also made of 448 consecutive out-patient
      hypertensives seen between March 1995 and April 1996. Five hundred and ninety
      three (17.9%) of 3317 acute medical admissions were ascribable to a
      cardiovascular cause (hypertension, heart failure, stroke); 171 (28.8%) of these
      died. One hundred and sixty-six (5.0%) had renal disease of whom 45 (27.1%) died,
      usually of end-stage renal disease. Among the 448 hypertensive out-patients,
      30.2% (110 out of 365) had a plasma creatinine >140 micromol/l (48 > or = 400
      micromol/l) and 25.5% (96 out of 376) had proteinuria. Eighty-nine of the 448 had
      a diastolic blood pressure > or =115 mm Hg; in this group 38 (42.7%) had a plasma
      creatinine of >140 micromol/l (and 18 or 20.2% > or =400 micromol/l). In
      conclusion, cardiovascular and renal disease are important contributors to
      morbidity and mortality among acute medical admissions to a large city hospital
      in Ghana. Among out-patient hypertensives renal disease is an important
      complication, especially in those with the more severe hypertension.

PMID- 9928751
TI  - The haemodynamic response to hyperinsulinaemia in hypertensive subjects.
AB  - In order to study if the vasodilatory action of insulin is impaired in essential
      hypertension, 24 untreated patients were challenged with a 2 h euglycaemic
      hyperinsulinaemic clamp (56 E/m2). Cardiac index (CI) was measured by thoracic
      impedance cardiography and leg blood flow (LBF) by Doppler ultrasound. During the
      clamp procedure a significant decline in blood pressure was seen (3.0-5.6% over
      120 min, P < 0.001). However, no significant effects on ejection fraction (+6 +/-
      8 s.d.%), CI (-1 +/- 2%), heart rate (+2 +/- 1%) or total peripheral resistance
      (TPRI, -0.5 +/- 2%) were found. LBF increased by 22 +/- 35% (P < 0.005). These
      haemodynamic effects of insulin were not related to age, sex, body mass index,
      blood pressure or the insulin-mediated glucose uptake during the clamp. In
      conclusion, insulin increased LBF, but no changes in CI and TPRI were seen in the
      hypertensive patients. Furthermore, no association between the ability of insulin
      to induce vasodilatation and to promote glucose uptake was seen.

PMID- 9928752
TI  - Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive
      patients with type II diabetes and impaired renal function.
AB  - The aim of this study was to compare the effects of ramipril and nitrendipine
      chronic treatment on urinary albumin excretion (UAE) in hypertensive patients
      with type II non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal
      function. A 2-year, prospective, randomised study was conducted on 51 men with a
      diastolic blood pressure (DBP) > or =95 and < or =105 mm Hg, stable NIDDM, serum
      creatinine between 1.6 and 3.0 mg/dl and persistent UAE >300 and <2000 mg/24 h.
      After a 3-month preliminary observation period, during which patients began a low
      protein, low-sodium diet, and a subsequent 4-week run-in period on placebo,
      patients were randomly treated with ramipril 5 mg or nitrendipine 20 mg for 2
      years. Both drugs similarly reduced BP without affecting glucose homeostasis. In
      the ramipril group UAE significantly decreased after only 3 months of treatment,
      whereas in the nitrendipine group a significant although lesser reduction in UAE
      was observed only after 1 year. During the second year the UAE% change was not
      statistically different between the two treatments. Serum creatinine and
      creatinine clearance showed no significant change with both drugs. The
      progression of renal insufficiency as assessed by the rate of reduction of
      creatinine clearance over the 2 years of the study was similar in the ramipril
      and the nitrendipine groups. In conclusion both ramipril and nitrendipine were
      associated with a decrease in UAE although such a reduction was earlier and more
      marked with ramipril. The decline of renal function did not differ significantly
      between the two treatments.

PMID- 9928753
TI  - Improved efficacy with maintained tolerability in the treatment of primary
      hypertension. Comparison between the felodipine-metoprolol combination tablet and
      monotherapy with enalapril. Swedish Multicentre Group.
AB  - In this multicentre, double-blind, parallel-group study, 120 out-patients with
      mild to moderate primary hypertension were randomised, after a 4-week single
      blind placebo run-in period, to a combination tablet of felodipine-metoprolol
      5/50 mg (Logimax, Mobloc, Astra) once daily or enalapril 10 mg once daily. If
      blood pressure (BP) remained suboptimally controlled after 4 weeks (supine
      diastolic BP >90 mm Hg 24-h post dose), the dose was doubled for a further 4
      weeks. After 8 weeks felodipine-metoprolol reduced supine BP significantly more
      than enalapril (19.7/12.0 mmHg and 11.1/7.2 mm Hg, respectively). The mean
      differences in change in BP between treatments were 8.6/4.8 mm Hg in favour of
      felodipine-metoprolol (P = 0.001/P <0.001). A statistically significant
      difference to the advantage of felodipine-metoprolol was also seen in standing
      BP. Even though the dose was increased in a larger proportion of patients in the
      enalapril group (61%) than in the felodipine-metoprolol group (40%), fewer
      enalapril-treated patients achieved adequate BP control (41% vs 63% on felodipine
      metoprolol, P <0.05). Both treatments were well tolerated. Three patients treated
      with felodipine-metoprolol and four with enalapril discontinued treatment due to
      adverse events. A similar number of patients reported adverse events in each
      treatment group. In conclusion, a combination tablet of felodipine-metoprolol
      5/50-10/100 mg once daily reduced BP more effectively than enalapril 10-20 mg
      once daily 24 h post dose. The result was expected, but a more important
      observation was that both treatments were tolerated to a similar degree.
      Obviously, a considerable BP reduction may be well tolerated, as was the main
      purpose to demonstrate in this study.

PMID- 9928754
TI  - Verapamil SR/trandolapril combination therapy for the elderly hypertensive
      patient. German VeraTran Hypertension Study Group.
AB  - A total of 254 elderly hypertensive patients (71 men and 183 women aged between
      63 and 92 years, diastolic blood pressure (DBP) 95-115 mm Hg inclusive) were
      treated with the fixed combination of verapamil SR/trandolapril following a 4
      week single-blind placebo run-in period. Treatment was started with a response
      dependent 3-step dose titration period. All patients were initiated at dose step
      1 (verapamil SR/trandolapril 120/0.5 mg o.d.) and if not normalised (DBP <90 mm
      Hg) titrated at 4-weekly intervals over dose step 2 (verapamil SR/trandolapril
      180/1 mg o.d.) to dose step 3 (verapamil SR/trandolapril 180/2 mg o.d.) during
      the first 12 weeks. After 3 months of treatment all patients not normalised were
      excluded from further participation in the study. The total duration of the
      treatment period was 6 months. Routine safety investigations were performed
      prior, during and on completion of the treatment period. Verapamil
      SR/trandolapril was highly effective in reducing blood pressure. At individual
      last visit during active treatment (also taking the non-responders into account),
      the mean reduction in SBP/DBP was 21.9/17.1 mm Hg (95% CI 19.8-24.1/16.1-18.1 mm
      Hg), with most of this reduction occurring during the first 3 months of
      treatment. After 6 months, 81.9% of the patients enrolled showed normalisation of
      DBP (<90 mm Hg) and 85% were responders (normalisation and/or reduction in DBP by
      at least 10 mm Hg). Normalisation and responder rates appeared to be comparable
      when stratified by age subgroups (63-69, 70-79 and > or =80 years) and were all
      greater than 80%. Verapamil SR/trandolapril was very well tolerated and there was
      no evidence of any clinically relevant changes in routine laboratory safety
      variables or resting ECG. In conclusion, the fixed dose combination of verapamil
      SR/trandolapril is an effective and safe alternative treatment for the elderly
      hypertensive patient.

PMID- 9928755
TI  - A randomised double-blind study comparing nifedipine GITS 20 mg and
      bendrofluazide 2.5 mg administered once daily in mild-to-moderate hypertension.
AB  - A multicentre, randomised, double-blind, parallel group comparison of nifedipine
      GITS 20 mg (Adalat LA) once daily and bendrofluazide 2.5 mg once daily in
      patients with mild-to-moderate hypertension was conducted. Two hundred patients
      with a diastolic blood pressure (BP) in the range 95 to 109 mm Hg were randomised
      to active treatment for 6 weeks. For the per-protocol efficacy population, both
      treatments resulted in clinically significant mean reductions of trough diastolic
      BP (nifedipine GITS -8.9 mm Hg, bendrofluazide -7.9 mm Hg) and systolic BP
      (nifedipine GITS -10.4 mm Hg, bendrofluazide -10.5 mm Hg). The study demonstrated
      that nifedipine GITS was 'at least equivalent' to bendrofluazide in the reduction
      of trough diastolic BP (one-sided upper 95% confidence limit, 0.5 mm Hg), where
      inequivalence had been pre-defined as a difference in mean diastolic BP of > or
      =5 mm Hg. Both drugs were well tolerated, the overall incidence of adverse events
      in the nifedipine GITS treatment group being 34.0% (34/100) and in the
      bendrofluazide treatment group being 29.0% (29/100). The commonest events
      (incidence > or =5%) were headache, constipation, 'flu syndrome and
      vasodilatation with nifedipine GITS and headache and nausea with bendrofluazide.
      An increased incidence of elevations of plasma urea and glucose was observed in
      patients treated with bendrofluazide (9.6% and 30.4% respectively) compared to
      those treated with nifedipine GITS (3.1% and 18.8% respectively). Nifedipine GITS
      20 mg once daily is 'at least equivalent' to bendrofluazide 2.5 mg once daily in
      reduction of blood pressure in patients with mild-to-moderate hypertension.

PMID- 9928756
TI  - High and non-suppressible plasma renin activity in a patient with aldosterone
      producing adenoma: pathophysiologic and diagnostic implications.
AB  - We describe a case of primary aldosteronism due to an aldosterone producing
      adenoma with high and non-suppressible plasma renin activity (PRA). She had
      suppressed PRA at initial diagnosis. This rose above the reference range for
      normal individuals over a period of 7 years with untreated hypertension. We
      discuss the possible pathophysiological causes of a rise in PRA in this clinical
      setting and suggest that underlying arteriolar disease due to prolonged
      hypertension may be the cause of increased and non-suppressible PRA in primary
      aldosteronism.

PMID- 9928757
TI  - Secondary hypertension and clinical genetics: usual presentation with unusual
      diagnosis.

PMID- 9928758
TI  - Evidence based medicine in LIVER.

PMID- 9928759
TI  - Effect of mesocaval interposition shunting and repeated sclerotherapy on blood
      levels of gastrointestinal regulatory peptides, amino acids, and lysosomal
      enzymes--a prospective randomised trial.
AB  - AIMS/BACKGROUND: Patients with liver cirrhosis and portal hypertension frequently
      exhibit a multitude of alterations of hormones and metabolism, but the relation
      of these alterations to liver function, degree of blood shunting, and hepatic
      encephalopathy remains unclear. METHODS: Twenty-four patients were randomised to
      mesocaval interposition shunt (MIS) and 21 patients to repeated sclerotherapy
      (ST). Several peptide hormones, amino acids and lysosomal enzymes were monitored
      during a 4 year follow-up period. RESULTS: Insulin and glucagon levels were
      elevated in the MIS group compared to pre-therapy levels, whereas the gastrin
      level was significantly higher in the ST group. Pancreatic polypeptide,
      somatostatin and vasoactive intestinal peptide levels were not affected by either
      treatment. The branched chain amino acids valine, leucine and isoleucine serum
      levels were all elevated after ST, and the arginine, proline and tyrosine levels
      were higher in the MIS group at follow-up. Other amino acids were not changed,
      neither were the lysosomal enzymes beta-hexosaminidase nor beta-glucoronidase
      during this longterm follow-up. CONCLUSION: MIS or repeated ST treatment only
      affected serum levels of hormones, amino acids and lysosomal enzymes to a limited
      extent. In this trial, the type of treatment had only a small influence on these
      parameters during long term follow-up.

PMID- 9928760
TI  - Vascularization of small hepatocellular carcinomas: correlation with
      differentiation.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is generally considered a
      hypervascular tumor when visualized by angiography. However, small HCCs are not
      always found to be hypervascular. METHODS: To evaluate this, 50 HCCs < or =3 cm
      in diameter were studied. The 50 tumors consisted of 16 well-differentiated HCCs,
      25 moderately differentiated HCCs, and 9 that were each a mixture of well- and
      moderately differentiated HCC. RESULTS: The mean number of portal tracts in the
      well-differentiated HCCs was 34% of the number in the surrounding nontumorous
      liver, and few intratumoral arterioles were seen. In contrast, the mean number of
      portal tracts in the moderately differentiated HCCs was 0.6% of the number in the
      surrounding nontumorous liver, and abundant intratumoral arterioles were seen.
      For HCCs that contained both well-differentiated and moderately differentiated
      tumor, the distribution of portal tracts and intratumoral arterioles in each
      portion was similar to that seen in well-differentiated or moderately
      differentiated HCC alone, respectively. HCCs that were larger than 1.5 cm in
      diameter had fewer portal tracts and more intratumoral arterioles than HCCs whose
      diameters were < or =1.5 cm. CONCLUSIONS: As small HCCs increase in size and
      become increasingly dedifferentiated, the number of portal tracts apparently
      decreases and intratumoral arterioles develop. These findings may reflect changes
      in the hemodynamics as the HCC develops.

PMID- 9928761
TI  - Expression of tumor necrosis factor-alpha gene during allograft rejection
      following rat liver transplantation.
AB  - BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha) is believed to play a
      role in hepatic allograft rejection. However, the specific cellular population
      responsible for TNF-alpha production during hepatic allograft rejection is not
      known. Circulating monocyte-macrophage cells are the primary systemic sources of
      TNF-alpha. In the liver, Kupffer cells are the main producers of TNF-alpha. In
      this study, we determined which cells are involved in TNF-alpha production during
      allograft rejection after orthotopic liver transplantation. METHODS: In situ
      hybridization was used to identify cells with TNF-alpha mRNA in the liver.
      Immunohistochemical staining with ED2 and ED3 was used to differentiate between
      cellular types (Kupffer cells versus infiltrating monocytes). To detect DNA
      fragmentation in liver cells, TdT-mediated biotin-dUTP nick-end labeling (TUNEL)
      was done. Studies were performed in the rat liver transplant model using
      rejecting (ACI to LEW) and non-rejecting (ACI to ACI) donor/recipient
      combinations. RESULTS: In the control group, cells with TNF-alpha mRNA were
      rarely observed. In the rejection group, TNF-alpha mRNA was observed in
      mononuclear cells that were mainly within the vessels of the portal region and
      occasionally in the sinusoids. The cells with the signals for TNF-alpha mRNA were
      ED2-negative and ED3-positive. DNA fragmentation was observed in hepatocytes as
      well as infiltrating mononuclear cells. CONCLUSIONS: The main producer of TNF
      alpha may be infiltrating mononuclear cells such as monocyte-macrophage cells
      rather than Kupffer cells during allograft rejection after liver transplantation.
      Circulating monocyte-macrophages may play a role in the control of allograft
      rejection.

PMID- 9928762
TI  - Co-expression of Bcl-2 protein and vascular endothelial growth factor in
      hepatocellular carcinomas treated by chemoembolization.
AB  - AIMS/BACKGROUND: Transcatheter arterial chemoembolization (TAE) of hepatocellular
      carcinoma (HCC) causes anoxia. Escape of cancer cells from anoxic injury may be
      enhanced by induction of proteins which provide resistance to apoptosis. METHODS:
      We examined HCCs immunohistochemically for Bcl-2, vascular endothelial growth
      factor (VEGF), p53, and Ki67. The staining intensity for VEGF, a protein induced
      by anoxia, was assessed morphometrically with a computer-assisted image-analyzer.
      RESULTS: The frequency of Bcl-2 positive cells was higher in HCCs that had
      undergone TAE (TAE HCC) than that in HCCs that had not undergone TAE (41.75+/
      15.06 vs. 1.01+/-0.79 cells/1000 cells, p = 0.0173). The frequency of p53- or
      Ki67-positive cells was not increased after TAE. Of 12 TAE HCCs, 7 had Bcl-2
      positive HCC cells and 6 had clusters of Bcl-2 positive cells. In contrast, 2 of
      11 HCCs that had not undergone TAE had only a few, sporadically distributed, Bcl
      2-positive cells. The staining intensity for VEGF was higher in Bcl-2 positive
      than in Bcl-2 negative areas (1.208+/-0.091 vs. 1.071+/-0.017, p = 0.0222).
      Furthermore, the VEGF staining intensity in Bcl-2 positive areas of TAE HCCs was
      higher than in Bcl-2 negative areas (1.296+/-0.126 vs. 1.066+/-0.024, p =
      0.0186), while in HCCs that had not undergone TAE the staining intensity was
      similar. CONCLUSIONS: TAE of HCC can induce Bcl-2 expression, possibly through
      anoxic stress.

PMID- 9928763
TI  - Immunohistochemical study on phenotypical changes of hepatocytes in liver disease
      with reference to extracellular matrix composition.
AB  - AIMS/BACKGROUND: Extracellular matrix (ECM) may affect the function and phenotype
      of hepatocytes. Phenotypic changes of hepatocytes in diseased liver were
      investigated with reference to ECM composition. METHODS: Immunohistochemistry was
      performed on biopsied liver samples from chronic viral hepatitis (CVH), primary
      biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and normal
      patients, using monoclonal antibodies for laminin, type IV collagen, cytokeratin
      19 (CK19) and epithelial glycoprotein (EGP), a protein homologous to nidogen.
      RESULTS: In normal controls, both EGP and CK 19 were expressed exclusively on
      biliary epithelia. Laminin and type IV collagen were expressed around portal bile
      ducts and blood vessels. Although type IV collagen was expressed in Disse's
      space, laminin was scarcely expressed. In all pathological livers, both EGP and
      CK 19 were expressed in proliferated bile ductules. In CVH with piecemeal
      necrosis, EGP was expressed on periportal hepatocytes, while CK19 expression was
      limited to a few hepatocytes. Laminin was expressed in Disse's space of
      periportal sinusoids, where EGP was expressed on hepatocytes. EGP expression on
      hepatocytes and laminin deposition in Disse's space were rare in PBC and PSC
      liver. CONCLUSION: These results suggest that hepatocytes transform into a
      phenotype similar to biliary epithelia and, laminin deposition in Disse's space
      (capillarization of sinusoids) may play a role in this phenotypic change.

PMID- 9928764
TI  - Primary biliary cystadenocarcinoma perforating the duodenum and left intrahepatic
      biliary tree--mimicking a hydatid cyst.
AB  - We report the case of a 76-year-old woman with biliary cystadenocarcinoma
      perforating the left biliary tree and exhibiting intra-tumoral gas bubbles
      resulting from invasion of the duodenum. The clinical history included subfebrile
      temperatures of 3 months duration, and pains associated with an abdominal mass in
      the right upper quadrant. Blood tests showed leucocytosis, and radiological
      studies revealed the features of a partially calcified septated tumor with
      nodular components combined with multiple gas-fluid levels, mimicking an infected
      hydatid cyst. Intraoperative ultrasonography, cholangiography and frozen section
      histology were necessary to prove the malignant nature of this cystic tumor.
      Provided that complete resection with strict adherence to oncological precepts is
      possible, the prognosis of cystadenocarcinoma is better than in hepatocellular or
      cholangiocellular carcinoma.

PMID- 9928765
TI  - Direct cytotoxicity of hypoxia-reoxygenation towards sinusoidal endothelial cells
      in the rat.
AB  - AIMS/BACKGROUND: Sinusoidal endothelial cells are the primary target of ischemia
      reperfusion injury following liver preservation. The present study was undertaken
      to examine the susceptibility of sinusoidal endothelial cells to hypoxia
      reoxygenation and the potential role of oxygen free radicals in the induction of
      cell injury. METHODS: Sinusoidal endothelial cells were isolated from rat liver.
      After 2 3 days of primary culture, the cells were exposed to hypoxia (N2/CO2
      95/5) for 120 min and reoxygenation (O2/CO2 95/5) for 90 min. Control cells were
      exposed to hypoxia alone, to 95% O2 alone or were maintained under normoxic
      conditions. Human umbilical vein endothelial cells were used as a model of
      vascular endothelial cells and submitted to the same protocol. Cell viability and
      lipid peroxidation were assessed by LDH leakage and malondialdehyde production,
      respectively. In order to test the potential role of xanthine oxidase and
      mitochondrial dysfunction in cell injury, the cells were treated with allopurinol
      and potassium cyanide (KCN) respectively. RESULTS: The different gaseous
      treatments did not affect LDH leakage in human umbilical vein endothelial cells.
      In sinusoidal endothelial cells, the sequential hypoxia-reoxygenation caused a
      significant increase in LDH release, malondialdehyde production and xanthine
      oxidase activity while hypoxia alone had no effect except on xanthine oxidase
      activity. Allopurinol inhibited xanthine oxidase without preventing cell injury
      or lipid peroxidation in this latter cell type. CONCLUSIONS: The results suggest
      that sinusoidal endothelial cells, as opposed to vascular endothelial cells, are
      susceptible to a direct cytotoxic effect of hypoxia-reoxygenation. This effect
      occurs in combination with an increase in xanthine oxidase activity and lipid
      peroxidation, although cell injury is mediated at least in part by mechanisms
      independent of xanthine oxidase such as mitochondrial dysfunction.

PMID- 9928766
TI  - Factors associated with progression of the disease before transplantation in
      patients with autoimmune hepatitis.
AB  - AIMS/BACKGROUND: Studies on transplanted patients may provide clinically useful
      data on factors influencing progression of autoimmune hepatitis (AIH) since
      transplantation rather than death may now be considered as the most likely end
      point of the disease. The aim of this work was to analyze risk factors related to
      progression of AIH before transplantation and provide guidelines for further
      prognostication with regards to the timing of transplantation. METHODS: 80 liver
      transplants in 68 patients with AIH were performed in our unit. The diagnosis was
      established on conventional clinical criteria. Parameters such as sex, age at
      diagnosis and transplantation or duration of the disease were evaluated in
      relation to: patient HLA DR status, disease presentation (aggressive or non
      aggressive), presence of anti-LKM antibodies and concurrent immune disease.
      RESULTS: AIH with concurrent immune disease occurred more commonly in females (90
      vs. 61%; p = 0.0075) and was linked with markedly slower progression of the
      disease (125 vs. 66 mo; p = 0.002) as compared to subjects without such
      association. AIH without concurrent autoimmune disease occurred significantly
      more commonly in patients with DR3 phenotype (p = 0.01). Patients with positive
      anti-LKM autoantibodies were younger at transplantation (25.6 vs. 43.5 yr; p =
      0.006) and had more rapid progression of their disease (14.3 vs. 103 mo; p =
      0.001). Unlike previously reported series of non-transplanted patients, all anti
      LKM positive subjects had no concurrent autoimmune disease. CONCLUSIONS:
      Coincidence with another autoimmune disease is associated with a significantly
      longer disease history prior to transplantation and may possibly reflect greater
      responsiveness to immunosuppressive therapy before grafting. AIH without
      concurrent autoimmune disease, particularly if associated with DR4 negative
      phenotype, male sex and anti-LKM antibodies may characterize patients with rapid
      progression of the disease. None of these factors had a significant influence on
      5 year survival after surgery.

PMID- 9928767
TI  - Remission of autoimmune hepatitis during pregnancy: a report of two cases.
AB  - Little is known about the evolution of autoimmune hepatitis (AIH) during
      pregnancy. Some authors reported worsening of the liver disease during pregnancy,
      whereas others reported stable conditions. We present two untreated patients who
      had remission of the autoimmune hepatitis in the second half of their
      pregnancies. One of the patients exhibited this phenomenon twice during two
      consecutive pregnancies. We speculate that the immunosuppressive effect of
      pregnancy induced remission of the autoimmune hepatitis in our patients.

PMID- 9928768
TI  - Proliferating cell nuclear antigen and Ki-67 labeling in hepatocellular nodules:
      a comparative study.
AB  - AIMS/BACKGROUND: The morphologic differential diagnosis of hepatocellular nodules
      (HCN) is frequently difficult and objective criteria would be useful in the
      categorization of such lesions. This study evaluated the proliferative activity
      of HCN, including regenerative, macroregenerative (MRN), cirrhotic, dysplastic,
      and hepatocellular carcinoma (HCC), as well as intranodular cytologic changes
      such as bile-stained hepatocytes, eosinophilia, clear, large cell (LCC) and small
      cell (SCC) change, by comparing the cellular density (CD), labeling indices (LI)
      and density (DP) of two proliferation markers. METHODS: Routinely processed
      tissue sections from 45 HCN from 17 adult liver explants were studied by
      immunohistochemistry for PCNA and Ki-67 (MIB-1). RESULTS: A progressive increase
      in LI from regenerative to dysplastic nodules to HCC was observed with both
      proliferation markers. The values of the two markers were significantly
      correlated (p<0.001). CD, PCNA and MIB-1 LI and DP values were significantly
      lower in regenerative compared to dysplastic nodules or HCC. MRNs had lower PCNA
      and MIB-1 LI and DP than regenerative nodules, but similar CD. There were no
      statistically significant differences in CD, PCNA, and MIB-1 LI and DP between
      dysplastic nodules and HCC, comparing high versus low grade dysplasia, or HCC
      smaller than 2 cm with those larger than 2 cm. The CD and proliferation indices
      LI and DP were higher in HCC than in the surrounding non-neoplastic parenchyma.
      Lesions with clear cell, eosinophilic and large cell change had CD, PCNA and MIB
      1 indices similar to those of regenerative nodules, while these were lower in
      bile-stained hepatocellular lesions (p<0.01). SCC showed CD, PCNA and MIB-1 LI
      and DP similar to HCC and higher than surrounding regenerative lesions (p<0.003).
      CONCLUSIONS: Our results suggest that PCNA and MIB-1 values are closely
      correlated in HCN. Regenerative nodules are characterized by low cellular
      proliferation, while dysplastic nodules are usually highly proliferative lesions
      and may represent an early stage in hepatocarcinogenesis. Hepatocellular lesions
      characterized by bile stained hepatocytes, eosinophilic, clear and large cell
      change have low proliferation rates and may not be significant for the
      development of malignancy.

PMID- 9928769
TI  - Spontaneous bacterial peritonitis by Campylobacter fetus in Budd-Chiari syndrome
      without liver cirrhosis.

PMID- 9928770
TI  - Problems of long-term spinal opioid treatment in advanced cancer patients.
AB  - Epidural and intrathecal techniques are well established techniques in cancer
      pain. However, several questions remain unresolved. The several problems of long
      term spinal opioid treatment in advance cancer patients were reviewed.
      Indications for the use of spinal opioids include patients treated by systemic
      opioids with effective pain relief but with unacceptable side effects, or
      unsuccessful treatment with sequential strong opioid drug trials despite
      escalating doses. Therefore, the previous aggressive treatment with systemic
      opioids would leave as failures patients with difficult pain syndromes
      unresponsive to opioids. The choice of external or totally implanted delivery
      systems is based on different clinical considerations. The use of externalized
      tunneled intrathecal catheters has not been associated with higher rates of
      complications and is easier to place and use at home in debilitated patients late
      in the course of their disease. The intrathecal administration has a lower
      incidence of catheter occlusion, lower malfunctioning rate, lower dose
      requirement, and more effective pain control. Due to the lower daily doses and
      volumes, intrathecal treatment proved to be more suitable for treatment at home
      by a continuous infusion than the epidural treatment. Advantages of infusion
      techniques are more evident when using local anesthetics, since intermittent
      administration of bupivacaine often results in motor paralysis and hemodynamic
      instability. Morphine is the opioid of choice. An epidural dose of 10% of the
      systemic dose is often used. However, intrathecal administration of opioids and
      bupivacaine may substantially improve pain relief in patients unresponsive to
      high epidural doses of these drugs, Bupivacaine-induced adverse effects,
      including sensory deficits, motor complaints, signs of autonomic dysfunction or
      neurotoxicity have been reported to not occur with bupivacaine doses less than 30
      60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of
      technical complication rates have been reported in the literature, most of them
      being associated with epidural catheters. Subcutaneous tunneling and fixation of
      the catheter, bacterial filters, minimum changes of tubings, careful exit site
      care weekly, site protection and monitoring of any sign of infection to prevent
      infection, and training for family under supervision, are recommended. Areas for
      additional research include the use of spinal adjuvants, the ideal spinal
      morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and
      long-term catheter management with appropriate home care programs.

PMID- 9928771
TI  - Assessment and treatment of neuropathic cancer pain following WHO guidelines.
AB  - Neuropathic pain syndromes are one of the major problems of cancer pain
      treatment. The present study surveys 593 cancer patients treated by a pain
      service following the WHO guidelines for relief of cancer pain. Of these, 380
      presented with nociceptive, 32 with neuropathic and 181 with mixed (nociceptive
      and neuropathic) pain. In patients with nociceptive, mixed and neuropathic pain,
      the average duration of evaluated pain treatment was 51, 53 and 38 days,
      respectively. Non-opioid or opioid analgesics were given to 99%, 96% and 79%,
      antidepressants to 8%, 25% and 19%, anticonvulsants to 2%, 22% and 38% and
      corticosteroids to 26%, 35% and 22% of patients, respectively. Systemic analgesia
      was supported by palliative antineoplastic treatment (48%, 56% and 38% of
      patients), nerve blocks (3%, 6% and 6%), psychotherapy (3%, 7% and 3%),
      physiotherapy (6%, 12% and 13%) and transcutaneous electric nerve stimulation
      (1%, 6% and 6%). Analgesic treatment resulted in a significant pain relief in all
      groups of patients, as the mean pain intensity (NRS) decreased from 66
      (nociceptive), 65 (mixed) and 70 (neuropathic) on admission to 26, 30 and 28
      after 3 days and 18, 17 and 21 at the end of survey. The total outcome of pain
      treatment was not predicted by the designation to nociceptive, mixed or
      neuropathic pain. In conclusion, neuropathic cancer pain is not intractable and
      can be relieved in the majority of patients by treatment following the WHO
      guidelines.

PMID- 9928772
TI  - A role for nerve growth factor in sympathetic sprouting in rat dorsal root
      ganglia.
AB  - The role of nerve growth factor (NGF) and glial-derived neurotrophic factor
      (GDNF) in sympathetic sprouting within the dorsal root ganglion was investigated.
      In nerve-intact rats, intrathecal NGF (1 mg/ml, 14 days) but not GDNF (1 mg/ml,
      14 days) induced extensive sprouting of tyrosine hydroxylase immunoreactive (TH
      IR) fibres and formation of pericellular TH-IR baskets within lumbar DRGs. TH-IR
      baskets were distributed equally to trkA-expressing and trkA-negative neuronal
      profiles. Sciatic nerve transection (14-21 days) induced TH-IR baskets within
      lumbar DRG's around neuronal profiles with both intact and lesioned axons. The
      percentage of neuronal profiles surrounded by TH-IR baskets following sciatic
      transection was unaffected following peripheral application of the NGF
      sequestering antibody, trkA-IgG (1 mg/ml, 14 days). Intracellular responses were
      recorded from sensory neurons in an in vitro DRG/peripheral nerve preparation
      following bath application of noradrenaline. In preparations from animals treated
      14 days previously with intrathecal NGF, 69% of neurons responded with
      depolarizing responses whilst 18% of neurons responded to bath applied
      noradrenaline in tissue prepared from naive animals. Our data indicate that
      sympathetic neurons sprout into the DRG in response to sciatic nerve injury and
      intrathecal NGF but not GDNF. Distribution of sympathetic sprouts within the DRG
      is independent of whether target neurons are injured or express trkA.
      Sequestration of NGF at the peripheral injury site does not influence basket
      formation within the DRG. It is likely that functional noradrenergic connections
      exist between sympathetic sprouts and sensory neuron cell bodies following
      exogenous NGF.

PMID- 9928773
TI  - Free radicals contribute to the reduction in peripheral vascular responses and
      the maintenance of thermal hyperalgesia in rats with chronic constriction injury.
AB  - We previously reported that the time frame and the extent of the changes in the
      peripheral neurogenic inflammatory response in the skin area, innervated by an
      injured nerve, coincide with those of pain behaviours. We raised the possibility
      that common factors might operate to modulate neuropathic pain and peripheral
      neurogenic processes in rats with chronic constriction nerve injury (CCI). In the
      present study we examined the role of free radicals in modulating the neurogenic
      vascular response and thermal hyperalgesia in rats with CCI of the sciatic nerve.
      Free radicals, via an interaction with nitric oxide (NO) to form peroxynitrite,
      have previously been implicated in the maintenance of thermal hyperalgesia in CCI
      rats. In this study, we induced CCI of the sciatic nerve and the activity of
      xanthine oxidase (XO), which catalyzes the formation of superoxide anions, was
      measured in the injured nerve. In addition, we examined the effect of
      antioxidants on thermal hyperalgesia and on the neurogenic vascular response to
      substance P (SP) perfused over the base of a blister induced on the hind footpad
      skin which is innervated by the injured sciatic nerve. Compared with the sham
      operated group, CCI rats had a significantly higher XO activity in the injured
      sciatic nerve and significantly reduced thermal threshold and peripheral
      neurogenic vascular response to SP. Treatment with antioxidants, superoxide
      dismutase (SOD) or tirilazad significantly improved the neurogenic vascular
      response while tirilazad treatment significantly alleviated thermal hyperalgesia.
      The results therefore, suggest that free radicals are elevated in CCI animals and
      that they contribute to the maintenance of thermal hyperalgesia and the reduction
      in peripheral microvascular blood flow in the area innervated by the injured
      nerve. We raise the possibility that common mechanisms may govern the changes in
      neuropathic pain and in the peripheral neurogenic vascular responses in tissues
      innervated by the injured nerve.

PMID- 9928774
TI  - A blinded pilot study investigating the use of diagnostic ultrasound for
      detecting active myofascial trigger points.
AB  - Myofascial trigger points (MFTPs) have been cited by numerous authors as the
      cause of local and referred pain which arises from muscle and its surrounding
      fascia. At present there is no reliable objective test which is capable of
      determining their presence. It was the purpose of this pilot study to assess the
      use of diagnostic ultrasound in determining any soft tissue changes in the region
      of clinically identified active MFTPs. Eleven subjects with clinically
      identified, unilateral, active MFTPs were examined with diagnostic ultrasound at
      the site of the trigger point as well as the asymptomatic, contralateral side.
      The analysis of the results of this pilot study found no correlation between the
      clinical identification of active MFTPs and diagnostic ultrasound.

PMID- 9928775
TI  - Changes of trapezius muscle blood flow and electromyography in chronic neck pain
      due to trapezius myalgia.
AB  - Chronic neck pain may increase the transmitter activity of neuropeptides in the
      upper cervical medulla causing impairment of the blood flow in the local muscle
      because of a lack of vasodilatatory substances excreted axonally. We have been
      using a new single-fibre technique for clinical determination of the
      microcirculation (LDF) in the trapezius muscles in relation to electromyography
      (EMG). This study pertains to the 76 patients (46 women and 30 men) who received
      a final diagnosis of chronic trapezius myalgia out of a total series of 300 cases
      with chronic neck pain which had been remitted to the National Insurance
      Administration Hospital in Tranas, Sweden, because their complaints interfered
      with their working ability. The purpose was to derive more objective medical
      information upon which to base rehabilitation. Sixty percent had continuous pain
      and 40% had pain after physical effort, or at work. Twenty healthy women
      volunteered to participate as a normal control group. The right and left
      trapezius muscles of all individuals were examined simultaneously with laser
      Doppler flowmetry (LDF) and surface EMG during a fatiguing series of stepwise
      increased contractions, each of 1 min duration with 1 min rest in between. The
      most painful side was compared with the opposite side in all patients and, in the
      female patients, also with the right shoulder of the healthy control women. The
      patients showed consistently low local blood flow in the painful side. The
      difference was statistically significant at low contraction intensities. Muscle
      tension was somewhat elevated, as evidenced by a slight increase of the rms-EMG
      that was statistically significant at high contraction intensities. The mean
      power frequency (MPF) of the EMG showed no change. The lowered local blood flow
      was not explained by a changed intramuscular pressure which is low in the
      trapezius during ordinary activities that do not normally impair the local blood
      flow (Larsson, S-E., Cai, H. and (Oberg, P.A., Microcirculation in the upper
      trapezius muscle during varying levels of static contraction, fatigue and
      recovery in healthy women. A study using percutaneous laser-Doppler flowmetry and
      surface electromyograpy, Eur. J. Appl. Physiol., 66 (1993) 483-488). We conclude
      that an impaired regulation of the microcirculation in the local muscle is of
      central importance in chronic trapezius myalgia, causing nociceptive pain which
      can be differentiated objectively from neuralgic neck-shoulder pain by the
      atraumatic technique described.

PMID- 9928776
TI  - A prospective, longitudinal study on patients with trigeminal neuralgia who
      underwent radiofrequency thermocoagulation of the Gasserian ganglion.
AB  - Outcome after radiofrequency thermocoagulation in patients with trigeminal
      neuralgia was assessed in a prospective, longitudinal study. Forty-eight
      consecutive patients with chronic facial pain presenting for surgery to a
      neurosurgeon were studied. Patients were assessed preoperatively by an
      independent clinician both clinically, and with the use of two questionnaires:
      the McGill Pain Questionnaire (MPQ) and the Hospital Anxiety and Depression (HAD)
      scale. From these assessments, two groups of patients were identified: 31 with
      pure trigeminal neuralgia (TN group) and 17 with trigeminal neuralgia together
      with atypical facial pain and mixed trigeminal neuralgia (MTN group). All
      underwent radiofrequency thermocoagulation at the level of the Gasserian
      ganglion. Patients were reviewed by the same clinician 3 months later and then
      followed up by a self-administered questionnaire at 6 months, 1 year, 2 years and
      3 years. The mean follow-up time was 30+/-12 months. The mean time to recurrence
      of pain was 40 months for the TN group and 36 months for the MTN group.
      Depression and anxiety dropped more significantly post-operatively in the TN
      group than the MTN group. TN group were more satisfied with their outcome,
      complained of fewer complications and were more willing to have repeat surgery if
      necessary than patients in MTN group. The number and severity of complications
      varied at different time points. Careful selection of patients for surgery using
      objective assessments will decrease morbidity and improve satisfaction. Physical
      morbidity and recurrence rates are insufficient to gauge outcomes. Psychological,
      sociological and patients' views must be included in evaluations.

PMID- 9928777
TI  - Growing pain: 10-year research trends in the study of chronic pain and headache.
AB  - This study examined trends in chronic pain (including chronic headache) research
      from 1986 to 1995. Medical and psychological citation databases were accessed to
      identify chronic pain publications and yearly trends. Data from the PsycLIT
      (psychological) database indicated significant growth over the time frame
      analyzed in both raw number of chronic pain publications and the percentage of
      articles devoted to chronic pain. Conversely, the Medline (medical) database
      showed a significant decline in the percentage of chronic pain articles over the
      time frame analyzed. Analyses revealed increases on the PsycLIT and Medline
      databases in the number of studies on elderly people, and the Medline database
      showed increases in the number of studies of chronic pain in children.
      Remarkably, there were significant increases on PsycLIT in the number of drug
      therapy studies for chronic pain, but a significant decrease was evident in the
      number of drug therapy articles abstracted on Medline. Factors that may be
      associated with these research trends are discussed, and future probable trends
      are anticipated.

PMID- 9928778
TI  - Differential effects of N-methyl-D-aspartate receptor blockade on nociceptive
      somatic and visceral reflexes.
AB  - N-methyl-D-aspartate (NMDA) receptors appear to play little part in nociceptive
      responses evoked by acute stimulation of normal somatic tissues, but rather are
      involved in hyperalgesic responses after peripheral injury and inflammation.
      Previous studies from this laboratory have shown important differences in the
      neural organization of somatic and visceral nociceptive pathways. Here, we have
      explored the role of NMDA receptors in processing acute visceral noxious input,
      compared with somatic noxious input. The left ureter was cannulated close to the
      bladder in adult female Wistar rats anaesthetized with pentobarbitone (50 mg/kg
      i.p). Graded distentions of the ureter (30 s, 25-80 mmHg) evoked increases in
      blood pressure. These responses were dose-dependently inhibited by the NMDA
      receptor ion channel blockers ketamine and memantine (ID50 = 2.4+/-1.6 and 14.5+/
      1.3 mg/kg, i.v.), and by the Merz glycine site antagonist Mrz 2/ 576 (ID50 =
      0.2+/-0.2 mg/kg). Graded pinch stimuli (30 s, 2-4 N) of one hind-paw evoked
      similar pressor responses which were not affected by ketamine (up to 10 mg/kg).
      Similarly, Mrz 2/576 did not affect responses to noxious pinch, whereas memantine
      (ID50 = 17+/-12 mg/kg) did inhibit responses to pinch stimuli. However, in the
      dose range used neither ketamine nor Mrz 2/576 inhibited a pressor response of
      non-nociceptive origin (produced by bilateral carotid occlusion) whereas
      memantine did. Thus the effects of memantine are likely due to a non-specific
      cardiovascular effect. These results show that NMDA receptor antagonists inhibit
      nociceptive reflexes evoked from the normal ureter, and suggest that NMDA
      receptors are involved in the processing of acute nociceptive inputs from
      viscera. We conclude that acute stimulation of normal visceral tissue provokes
      intense responses that recruit neural mechanisms mediated by NMDA receptors.
      However, in somatic pathways, these mechanisms are recruited only by an enhanced
      peripheral input such as that produced after injury or inflammation.

PMID- 9928779
TI  - Windup leads to characteristics of central sensitization.
AB  - Central sensitization refers to enhanced excitability of dorsal horn neurons and
      is characterized by increased spontaneous activity, enlarged receptive field (RF)
      areas, and an increase in responses evoked by large and small caliber primary
      afferent fibers. Sensitization of dorsal horn neurons often occurs following
      tissue injury and inflammation and is believed to contribute to hyperalgesia.
      Windup refers to the progressive increase in the magnitude of C-fiber evoked
      responses of dorsal horn neurons produced by repetitive activation of C-fibers.
      In the present study, we tested the hypothesis that windup leads to central
      sensitization. Recordings were made from rat nociceptive dorsal horn neurons
      classed as wide dynamic range. Windup was produced by conditioning stimuli in a
      train of 12 electrical pulses (0.5 ms duration) applied to the RF at intensities
      three times the threshold for excitation of C-fibers and at a frequency of 0.5
      Hz. Single electrical stimuli applied outside the RF never evoked responses
      except when delivered following conditioning stimulation inside the RF,
      indicating an expansion of the RF following windup. C-Fiber conditioning stimuli
      applied outside the RF also increased the response evoked by a single stimulus
      and increased the total number of spikes evoked by a train of electrical stimuli
      delivered inside the RF. Although both A- and C-fibers were activated,
      conditioning stimuli did not alter subsequent responses evoked by stimulation of
      A-fibers. Enhanced responsivity to C-fiber input following windup produced by
      stimulation inside the RF at a frequency of 0.5 Hz could be maintained for
      approximately 100 s by stimuli delivered at 0.1 Hz, a frequency that itself
      cannot produce windup. It is concluded that neuronal events leading to windup
      also produce some of the classical characteristics of central sensitization
      including expansion of RFs and enhanced responses to C- but not A-fiber
      stimulation. Thus, windup may be a useful tool to study mechanisms underlying
      certain characteristics of central sensitization related to C-fiber activity.

PMID- 9928781
TI  - Evaluation of the use of a pain diary in chronic cancer pain patients at home.
AB  - Systematic assessment of pain is the basis for adequate pain treatment. In the
      home situation, however, it is difficult to assess patients' pain intensity. A
      group of 159 cancer patients who had been admitted to a cancer hospital with pain
      caused by cancer, cancer therapy, or illness that persisted for at least 1 month
      received a pain diary. These patients were asked to register their pain intensity
      at home. Patients were instructed by a nurse to record their Present Pain
      Intensity on a scale from 0-10 once every morning and every evening for a period
      of 2 months. In this study, the use of a pain diary in cancer pain patients at
      home was evaluated. To determine the effects of the pain diary, patients were
      interviewed at baseline, at 2, 4, and 8 weeks postdischarge. Pain intensity
      scores were obtained both by patient interviews and from the pain diary. Results
      show that the use of a pain diary is an appropriate way to assess patients' pain
      intensity at home. Patients' compliance was high (86%), even in seriously ill
      patients. When comparing pain scores obtained by patient interview with scores
      obtained by pain diary, results showed that Present Pain Intensity scores, rather
      than Average Pain Intensity scores, should be used in both the clinical and the
      home setting because patients' recall accuracy depends, in part, on the stability
      of the pain. Because the pain intensity scores fluctuate greatly during the day
      and over a period of time, the use of a pain diary is useful in the home setting.
      In 60% of the patients, completing the pain scores helped them to cope with the
      pain.

PMID- 9928780
TI  - Peripherally administered sufentanil inhibits pain perception after postpartum
      tubal ligation.
AB  - The clinical effectiveness of locally administered opioids is still under
      discussion; in particular, the potency of morphine in settings other than intra
      articular arthroscopy has been questioned. We developed another pain model,
      postpartum resection of the fallopian tubes for sterilisation, in which each
      patient serves as her own control when one side is infiltrated with the active
      drug (in this study sufentanil 5 mg) and the contralateral side with normal
      saline. In the control group both sides are infiltrated with plain saline. After
      30 min from the end of anaesthesia onwards, 26 out of 30 patients observed
      significant pain relief on the side of the sufentanil infiltration, which in 11
      patients lasted until the end of the observation period 24 h postoperatively; no
      difference was observed in the control group. In our pain model with a high assay
      sensitivity, the infiltration of one side with the lipophilic test drug,
      sufentanil, caused local analgesia in primarily non-inflamed tissue. The use of
      each patient as her own control excluded inter-subject bias.

PMID- 9928782
TI  - The long lasting effects of peripheral nerve blocks for trigeminal neuralgia
      using high concentration of tetracaine dissolved in bupivacaine.
AB  - The management of trigeminal neuralgia in older patients who do not want
      neurolytic block and/or surgical treatment may be problematic. This paper
      describes three patients who had first and/or second division trigeminal
      neuralgia. The analgesic effects of infraorbital nerve block using 0.5%
      bupivacaine or 1% mepivacaine dissipated within a few days, however, the effects
      of nerve blocks using 4% tetracaine dissolved in 0.5% bupivacaine continued for
      more than 3 months. Hypesthesia was observed in two patients within a week
      following the block, but sensory level returned to normal within 2 weeks and
      there were no further complications in any patient.

PMID- 9928783
TI  - Cortical regions contributing to the anterior commissure in man.
AB  - The human anterior commissure is believed, by extrapolation from data obtained in
      macaque monkeys, to convey axons from the temporal and orbitofrontal cortex.
      Reports of interhemispheric transfer and sexual dimorphism related to the
      anterior commissure, however, make more precise data on the human anterior
      commissure desirable. We investigated the connectivity of the human anterior
      commissure in six adults (male and female) that had circumscribed hemispheric
      lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal
      white matter using the Nauta for anterogradely degenerating axons. Axons
      originating in the inferior part of temporal or occipital lobes, occipital
      convexity and possibly central fissure and prefrontal convexity were found to
      cross the midsagittal plane in the anterior commissure. The largest contingent of
      commissural axons originated in the inferior part of the temporal lobe; it
      displayed a roughly topographic organization, preferentially running through the
      inferior part of the commissure. The inferior temporal contingent seemed to reach
      homotopic and heterotopic targets in the opposite hemisphere. Among the latter
      were the amygdala and possibly the orbitofrontal cortex. The present data suggest
      that the human anterior commissure conveys axons from much larger territories
      than expected from work on non-human primates. Similarly to the human and non
      human primate corpus callosum, the anterior commissure is roughly topographically
      organized and participates in heterotopic connectivity.

PMID- 9928784
TI  - Neural circuits underlying ketamine-induced oculomotor behavior in the rat: 2
      deoxyglucose studies.
AB  - Time-related changes in oculomotor function and of metabolic activity patterns in
      selected brain networks, as assessed by the quantitative 2-deoxyglucose
      technique, were investigated in Long-Evans rats following intraperitoneal
      administration of a ketamine anesthetic dose. During ketamine-induced anesthesia
      a nystagmic-like behavior was present, characterized by uni-directional slow
      ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye
      movements; all quick movements were executed in the horizontal direction, were
      strictly confined to an ocular hemifield of vision, and were followed by a
      backward (centripetal) drift. A metabolic hyperactivity was found in the dorso
      medial shoulder region of the frontal cortex, corresponding to the rat saccadic
      cortical generator area, whereas functional activity levels were decreased in
      cerebellum and in several brainstem regions, including portions of the reticular
      formation and medial vestibular nuclei, putatively indicated as the locus of the
      oculomotor neural integrator. Starting 2 h after drug injection, a gradual
      recovery of oculomotor function occurred, with the disappearance of slow ocular
      drifts. However, an almost uninterrupted sequence of individual saccades was
      still present. Significant metabolic increases were found at this time in the
      cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian
      reticular formation and oculomotor nuclei, the cerebellar vermis and
      paraflocculus. In medial vestibular nuclei, metabolic levels were
      undistinguishable from controls. These results suggest different concentration
      dependent actions of ketamine on cortical and subcortical circuits involved in
      saccade generation and gaze holding. These effects are likely to be related at
      least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.

PMID- 9928785
TI  - Sympathetic sprouting: no evidence for muscarinic modulation of noradrenaline
      release in hippocampal slices of rats with fimbria-fornix lesions.
AB  - Lesions of the septohippocampal pathways elicit sprouting of sympathetic fibers
      from the superior cervical ganglion, a phenomenon which, within a few months,
      raises the hippocampal noradrenaline (NA) content above normal. In peripheral
      sympathetic fibers, the release of NA is modulated via presynaptic muscarinic
      receptors. Such receptors have not been detected so far on terminals of
      noradrenergic neurons originating in the locus coeruleus. Whether the release of
      NA could become sensitive to muscarinic modulation in the hippocampus following
      sympathetic fiber ingrowth was the major question in this experiment. The
      contribution of presynaptic nicotinic receptors was also studied. Slices from the
      ventral hippocampus (only dentate gyrus+CA3 region) of sham-operated (SHAM) and
      fimbria-fornix lesioned (LES) Long-Evans rats (8-10 months after surgery) were
      preincubated with [3H]NA and stimulated either once (S1) with 100 microM nicotine
      or (in parallel experiments) twice electrically (S1, S2), using conditions (six
      pulses 100 Hz, 2 ms, 28 mA, 4 V/chamber) that precluded autoinhibition. In
      experiments using electrical stimulation, the superfusion medium contained
      desipramine (1 microM). In LES rats, the tissue NA content had almost doubled
      (171% of SHAM levels), but the amount of [3H]NA taken up by the slices was
      unchanged, and the overflow evoked at S1 by both nicotinic and electrical
      stimulation was significantly reduced in comparison with SHAM rats. In both
      groups, the addition of oxotremorine or oxotremorine+atropine (1 microM, each)
      before S2 failed to affect the electrically evoked overflow of 3H. Nicotine
      induced NA release was inhibited by hexamethonium (100 microM) in both groups,
      although significantly less potently in LES rats. Tissue activity of choline
      acetyltransferase was reduced in LES rats to 15% of SHAM levels and the 5
      hydroxytryptamine content was also strongly diminished (38% of SHAM values). It
      is concluded that lesion-induced sprouting of sympathetic fibers into the
      hippocampus is not accompanied by the emergence of a muscarinic modulation of NA
      release in this tissue, and that the sensitivity of the presynaptic stimulatory
      effect of nicotine was modified by the lesion.

PMID- 9928786
TI  - Nystagmus induced by circular head shaking in normal human subjects.
AB  - We recorded three-dimensional eye and head movements during circular, horizontal,
      vertical, and torsional head shaking in six human subjects with normal vestibular
      function. With circular head shaking, the stimulation of the canals by the
      termination of the head movement is similar to that following a step in velocity
      about the naso-occipital axis. A large torsional nystagmus with slow phase eye
      velocity of about 20 degrees/s was observed upon cessation of circular head
      shaking. The three-dimensional eye movements expected from stimulation of the
      semicircular canals by the head-shaking maneuvers were calculated. The predicted
      activation of the canals was determined by projecting the head velocity (in head
      coordinates) into the canal planes and then processing the signal with the
      transfer function of the canals. The torsional eye velocity components predicted
      by the stimulation of the canals matched the recorded ones. We observed small
      horizontal eye velocities that could not be predicted by the stimulation of the
      canals alone. No eye movements were observed after the end of head shaking about
      a fixed horizontal or vertical axis. The eye velocities following the termination
      of head oscillations in the roll plane were small. The analysis methods developed
      for this study may be useful in the investigation of eye movements elicited by
      other types of three-dimensional head movements.

PMID- 9928787
TI  - The time-course of preparatory spinal and cortico-spinal inhibition: an H-reflex
      and transcranial magnetic stimulation study in man.
AB  - In a previous study where reaction-time methods were combined with transcranial
      magnetic stimulation (TMS) of the motor cortex, cortico-spinal excitability was
      shown to reflect time preparation. Provided that subjects can accurately estimate
      time, the amplitude of motor-evoked potentials (MEPs) diminish progressively
      during the interval separating the warning signal from the response signal (i.e.,
      the foreperiod). On the other hand, several experiments have demonstrated that
      the amplitude of the Hoffman (H) reflex elicited in prime movers diminishes
      during the foreperiod of reaction-time tasks. The aim of the present study was to
      compare the time course of the respective decrements of H-reflex and MEP
      amplitude during a constant 500-ms foreperiod. The subjects (n=8) participated in
      two experimental sessions. In one session, H-reflexes were induced in a tonically
      activated, responding hand muscle, the flexor pollicis brevis, at different times
      during the foreperiod of a visual-choice reaction-time task. In the other
      session, motor potentials were evoked in the same muscle by TMS of the motor
      cortex delivered in the same behavioral conditions and at the same times as in
      the first session. The results show that both H-reflexes and MEPs diminish in
      amplitude during the foreperiod, which replicates and extends previous findings.
      Interestingly, the time constants of the two decrements differed. There was a
      facilitatory effect of both electrical and magnetic stimulations on the subject's
      performance: reaction time was shorter for the trials during which a stimulation
      was delivered than for the no-stimulation trials. This facilitation was maximal
      when the stimulations were delivered simultaneously with the warning signal and
      vanished progressively with stimulation time.

PMID- 9928788
TI  - The oculomanual coordination control center takes into account the mechanical
      properties of the arm.
AB  - When the eyes and arm are involved in a tracking task, the characteristics of
      each system differ from those observed when they act alone: smooth pursuit (SP)
      latency decreases from 130 ms in external target tracking tasks to 0 ms in self
      moved target tracking tasks. Two models have been proposed to explain this
      coordination. The common command model suggests that the same command be
      addressed to the two sensorimotor systems, which are otherwise organized in
      parallel, while the coordination control model proposes that coordination is due
      to a mutual exchange of information between the motor systems. In both cases, the
      interaction should take into account the dynamic differences between the two
      systems. However, the nature of the adaptation depends on the model. During self
      moved target tracking a perturbation was applied to the arm through the use of an
      electromagnetic brake. A randomized perturbation of the arm increased the arm
      motor reaction time without affecting SP. In contrast, a constant perturbation
      produced an adaptation of the coordination control characterized by a decrease in
      arm latency and an increase in SP latency relative to motor command. This brought
      the arm-to-SP latency back to 0 ms. These results support the coordination
      control model.

PMID- 9928789
TI  - Neurones in the dorsolateral periaqueductal grey matter in coronal slices of rat
      midbrain: electrophysiological and morphological characteristics.
AB  - Intracellular recordings using the whole-cell patch-clamp configuration were made
      from 87 neurones in the dorsolateral "aversive" region of the periaqueductal grey
      matter (PAG) in coronal slices of rat midbrain. Camera lucida reconstructions
      made of 28 of the cells, which had been filled with biocytin, revealed round,
      triangular or oval cell bodies 11-40 microm in diameter. Between two and seven
      primary dendrites were present, which branched further, often becoming varicose.
      The dendritic tree was always contained within the dorsal half of the PAG.
      Biocytin-filled axons could be followed for 177-2315 microm from the soma. The
      axons typically travelled to the perimeter of the dorsal half of the ipsilateral
      PAG, before either turning ventrolaterally to run parallel to the tecto
      bulbopsinal fibres or continuing their trajectory into the deep collicular layers
      or the mesencephalic reticular formation. Electrophysiologically, two functional
      categories of cells could be distinguished: type-A cells (30%) showed inward
      rectification at membrane voltages in excess of -77 mV and had short action
      potentials (1.6+/-0.07 ms), which were followed by a biphasic afterpolarisation
      characterised by an initial fast and a later slow phase. Only 18.5% of the type-A
      cells were spontaneously active (<4 Hz). The second category of cell (type B, 70%
      of the recorded population) did not show rectification and had longer-duration
      action potentials (2.1+/-0.07 ms), which showed a smooth decay of the
      afterhyperpolarisation phase. Approximately one third (37%) of the type-B cells
      fired spontaneously (<4 Hz). The gross morphology of the two types of cells was
      similar. However, in type-A cells (n=6), the axons could be seen to originate
      from the cell soma, whereas, in the majority of the type-B population (10/13),
      the axon arose from a primary dendrite. The results show that coronal slices of
      midbrain contain a viable population of "output" or "projection" neurones, which
      are accessible to electrophysiological and pharmacological investigation. In
      conscious animals, efferent output from this part of the PAG is concerned with
      mediating the autonomic and somatomotor changes which are characteristic
      components of aversive emotional behaviour. The output neurones should therefore
      reflect the net level of excitability in the PAG in relation to its functional
      activity.

PMID- 9928790
TI  - Evidence suggesting that a transcortical reflex pathway contributes to cutaneous
      reflexes in the tibialis anterior muscle during walking in man.
AB  - Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of
      the tibialis anterior (TA) EMG-activity at a latency of 70-95 ms in the early and
      middle swing phase of human walking. The present study investigated the
      underlying mechanism for this facilitation. In those subjects in whom it was
      possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17
      tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve
      (3 shocks, 3-ms interval, 2.0-2.5x perception threshold) was found to have the
      same latency in the swing phase of walking. The facilitation observed during
      tonic dorsiflexion has been suggested to be -- at least partly -- mediated by a
      transcortical pathway. To investigate whether a similar mechanism contributes to
      the facilitation observed during walking, magnetic stimulation of the motor
      cortex (1.2x motor threshold) was applied in the early swing phase at different
      intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the
      subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were
      more facilitated by prior sural-nerve stimulation (conditioning-test intervals of
      50-80 ms) than the algebraic sum of the control MEP and the cutaneous
      facilitation in the EMG when evoked separately. In four of these subjects, a
      tibialis anterior H-reflex could also be evoked during walking. In none of the
      subjects was an increase of the H-reflex similar to that for the MEP observed. In
      five experiments on four subjects, MEPs evoked by magnetic and electrical
      cortical stimulation were compared. In four of these experiments, only the
      magnetically induced MEPs were facilitated by prior stimulation of the sural
      nerve. We suggest that a transcortical pathway may also contribute to late
      cutaneous reflexes during walking.

PMID- 9928791
TI  - Preparatory trunk motion accompanies rapid upper limb movement.
AB  - Evaluation of trunk movements, trunk muscle activation, intra-abdominal pressure
      and displacement of centres of pressure and mass was undertaken to determine
      whether trunk orientation is a controlled variable prior to and during rapid
      bilateral movement of the upper limbs. Standing subjects performed rapid
      bilateral symmetrical upper limb movements in three directions (flexion,
      abduction and extension). The results indicated a small (0.4-3.3 degrees) but
      consistent initial angular displacement between the segments of the trunk in a
      direction opposite to that produced by the reactive moments resulting from limb
      movement. Phasic activation of superficial trunk muscles was consistent with this
      pattern of preparatory motion and with the direction of motion of the centre of
      mass. In contrast, activation of the deep abdominal muscles was independent of
      the direction of limb motion, suggesting a non-direction specific contribution to
      spinal stability. The results support the opinion that feedforward postural
      responses result in trunk movements, and that orientation of the trunk and centre
      of mass are both controlled variables in relation to rapid limb movements.

PMID- 9928792
TI  - From balance regulation to body orientation: two goals for muscle proprioceptive
      information processing?
AB  - This study was based on the assumption that the central processing of
      proprioceptive inputs that arise from numerous muscles contributes to both
      awareness and control of body posture. The muscle-spindle inputs form a
      "proprioceptive chain" which functionally links the eye muscles to the foot
      muscles. Here, we focused on the specific contribution of two links in the
      control of human erect posture by investigating how proprioceptive messages
      arising from ankle and neck muscles may be integrated by the central nervous
      system. Single or combined mechanical vibrations were applied to different muscle
      tendons at either one (ankle or neck) or both (ankle plus neck) body levels. The
      amplitude and the specific direction of the resulting oriented body tilts were
      analyzed by recording the center of foot pressure (CoP) through a force platform
      with four strain gauges. The results can be summarized as follows: (1) the
      vibration-induced whole-body tilts were oriented according to the muscles
      stimulated; furthermore, the tilts were in opposite directions when neck or ankle
      muscles on the same side of the body were stimulated; (2) except for the ankle
      antagonist muscles, co-vibrating adjacent or antagonist muscles at the same body
      level (ankle or neck) resulted in body sways, whose orientation was a combination
      of those obtained by stimulating these muscles separately; and (3) likewise, co
      vibrating ankle and neck muscles induced whole-body postural responses, whose
      direction and amplitude were a combination of those obtained by separate
      vibration. We conclude that the multiple proprioceptive inputs originating from
      either one or both body levels may be co-processed in terms of vector-addition
      laws. Moreover, we propose that proprioceptive information from ankle and neck
      muscles may be used for two tasks: balance control and body orientation, with
      central integration of both tasks.

PMID- 9928793
TI  - Studies of lectin receptors of rat microglia in culture: receptor distribution
      and internalization.
AB  - The present study examined the lectin labeling of diverse morphological forms of
      microglia in culture. Similar to amoeboid microglial cells in vivo, polymorphic
      microglia showed lectin labeling at their plasma membranes, as well as in a few
      cytoplasmic vesicles and vacuoles. This labeling pattern was observed in cultured
      microglia incubated with isolectin at 4 degrees C for 30 min. Five minutes after
      the temperature was raised to 37 degrees C, the surface lectin receptors appeared
      to be internalized, as shown by the occurrence of many subsurface lectin-labeled
      vesicles, vacuoles and tubule-like structures. With longer incubation (up to 1-2
      h at 37 degrees C), many lysosomes and a few trans-Golgi saccules and associated
      lysosome-like structures became labeled. Concomitant with these changes was a
      reduction of lectin labeling at the plasma, with labeling having vanished in most
      of the cells after 1-2 h of incubation. By 24 h, only a few cells retained
      surface lectin labeling. It appears, therefore, that irrespective of morphology,
      lectin labeling (including its intracellular pathway) of microglia in culture
      parallels that of amoeboid microglia in vivo. This would offer a useful model for
      the study of lectin turnover in microglia and help to explain the roles of such
      receptors in microglial differentiation and function.

PMID- 9928794
TI  - Grip force adjustments induced by predictable load perturbations during a
      manipulative task.
AB  - The experiment examined the anticipatory modulation of grip force with respect to
      load force during a drawer opening task. An impact force was introduced by a
      mechanical stop that arrested movement of the pulling hand. The results showed a
      typical grip force profile which consisted of two evolving phases, one to control
      drawer movement onset, and the other to secure grip force at the expected impact.
      Initially, grip force increased with the load force that was developed to
      overcome the inertia of the drawer. After the first peak, a small decline was
      observed, followed by a proactive grip force increase prior to the time of
      impact. During this ramp-like increase of grip force, load force remained
      unchanged. In addition, a reactive response was triggered by the impact. That
      anticipatory control with respect to an impact force is not innate but, rather,
      is learned by experience was evidenced by a comparison of adults and children.
      Whereas adults made the characteristic grip force adjustments to anticipate the
      impact, children used a probing strategy with irregular build-up of force until
      impact. Furthermore, adults calibrated the second phase of the grip force profile
      in the initial trials of the task, indicating that grip force was rapidly updated
      with information related to the impact force. The present results demonstrate
      that grip-load force coordination during manipulation is a necessity for dealing
      with destabilizing load perturbations produced by self-induced movement and
      impact forces. It is concluded that grip force is adjusted automatically, but in
      a flexible manner, to secure grip in accordance with the characteristics of the
      pulling synergy.

PMID- 9928795
TI  - Forearm postural control during unloading: anticipatory changes in elbow
      stiffness.
AB  - In this study, the equilibrium-point hypothesis of muscle-torque generation is
      used to evaluate the changes in central control parameters in the process of
      postural-maintenance learning. Muscle torque is described by a linear spring
      equation with modifiable stiffness, viscosity, and equilibrium angle. The
      stiffness is considered to be the estimation of the central command for
      antagonist-muscle coactivation and the equilibrium angle to be the estimation of
      the reciprocal command for a shift of invariant characteristics of the joint. In
      the experiments, a load applied to the forearm was released. The subjects were
      instructed to maintain their forearm in the initial horizontal position. Five
      sessions of approximately twenty trials each were carried out by eight subjects.
      During two "control" series, the load release was triggered by the experimenter.
      During three "learning" series, the load supported by one forearm was released by
      the subject's other hand. The elbow-joint angle, the angular acceleration, and
      the external load on the postural forearm were recorded. These recordings as well
      as anthropometric forearm characteristics were used to calculate the elbow-joint
      torque (which we called "experimental"). Linear regression analysis was performed
      to evaluate the equilibrium angle, joint stiffness, and viscosity at each trial.
      The "theoretical" torque was calculated using a linear spring equation with the
      found parameters. The good agreement observed between experimental and
      theoretical joint-torque time courses, apart from the very early period following
      unloading, argues in favor of the idea that the movement was mainly performed
      under a constant central command presetting the joint stiffness and the
      equilibrium angle. An overall increase in the stiffness occurred simultaneously
      with a decrease in the equilibrium angle during the "learning" series in all the
      subjects. This suggests that subjects learn to compensate for the disturbing
      effects of unloading by increasing the joint stiffness. The mechanism possibly
      responsible for the presetting of the central control parameters is discussed.

PMID- 9928796
TI  - Segmentation of endpoint trajectories does not imply segmented control.
AB  - While it is generally assumed that complex movements consist of a sequence of
      simpler units, the quest to define these units of action, or movement primitives,
      remains an open question. In this context, two hypotheses of movement
      segmentation of endpoint trajectories in three-dimensional human drawing
      movements are reexamined: (1) the stroke-based segmentation hypothesis based on
      the results that the proportionality coefficient of the two-thirds power law
      changes discontinuously with each new "stroke," and (2) the segmentation
      hypothesis inferred from the observation of piecewise planar endpoint
      trajectories of three-dimensional drawing movements. In two experiments human
      subjects performed a set of elliptical and figure eight patterns of different
      sizes and orientations using their whole arm in three dimensions. The kinematic
      characteristics of the endpoint trajectories and the seven joint angles of the
      arm were analyzed. While the endpoint trajectories produced similar segmentation
      features to those reported in the literature, analyses of the joint angles show
      no obvious segmentation but rather continuous oscillatory patterns. By
      approximating the joint angle data of human subjects with sinusoidal
      trajectories, and by implementing this model on a 7-degree-of-freedom (DOF)
      anthropomorphic robot arm, it is shown that such a continuous movement strategy
      can produce exactly the same features as observed by the above segmentation
      hypotheses. The origin of this apparent segmentation of endpoint trajectories is
      traced back to the nonlinear transformations of the forward kinematics of human
      arms. The presented results demonstrate that principles of discrete movement
      generation may not be reconciled with those of rhythmic movement as easily as has
      been previously suggested, while the generalization of nonlinear pattern
      generators to arm movements can offer an interesting alternative to approach the
      question of units of action.

PMID- 9928797
TI  - Dermatoses in cement workers in southern Taiwan.
AB  - Construction workers are known to have occupational dermatoses. The prevalence of
      such dermatoses was unknown in Taiwanese construction workers. The objective of
      this study was to determine the work exposure, prevalence of skin manifestations,
      and sensitivity to common contact allergens in cement workers of southern Taiwan.
      A total of 1147 current regular cement workers were telephone-interviewed about
      skin problems during the past 12 months, work exposure, and personal protection.
      Among those interviewed, 166 were examined and patch tested with common contact
      allergens. A high % of cement workers reported skin problems in the past 12
      months. More men (13.9%) reported skin problems possibly related to work than
      women (5.4%). Prevalence was associated with lower use of gloves, duration of
      work as cement worker, and more time in jobs involving direct manual handling of
      cement, especially tiling. A high % of dermatitis was noted in the 166 workers
      examined, which correlated with reported skin problems. On patch testing,
      construction workers had a high frequency of sensitivity to chromate. Sensitivity
      to chromate or cobalt was associated with reported skin problems, or dorsal hand
      dermatitis on examination. These workers' dermatitis was under-diagnosed and
      inadequately managed. It is concluded that cement workers in southern Taiwan had
      a high prevalence of skin problems related to cement use. Protective measures,
      work practice, and physician education should be improved to prevent or manage
      such problems.

PMID- 9928798
TI  - Thimerosal positivities: patch testing to methylmercury chloride in subjects
      sensitive to ethylmercury chloride.
AB  - The aim of this paper was to evaluate whether methylmercury chloride (MeHgCl)
      aq., when patch tested in a group of thimerosal-positive subjects reacting to
      ethylmercury chloride (EtHgCl), might be a reliable model for the better
      understanding of interactions between alkylmercury compounds and the skin. 19 out
      of 21 consecutive patients who previously had given positive patch-test reactions
      to both ethylmercury chloride 0.0165% eth.(EtHgCl, 0.615 mM) and MeHgCl 0.031%
      aq.(1.23 mM), and negative reactions to thiosalicylic acid 0.05% (3.24 mM)
      aq./eth. 50/50, were repatch tested to 8 microl of MeHgCl 0.031% aq. and to 8
      microl of aq. solutions containing MeHgCl mixed with cysteine, glutathione,
      ZnSO4, MgSO4, MnSO4, ZnCl2, MgCl2 and MnCl2, respectively. The results showed
      that cysteine, glutathione and Zn(II) salts were able to abolish the positive
      reactions, demonstrating the role played by both thiol groups and Zn(II) itself.
      Patch tests concomitantly carried out in 16 out of 19 patients to 8 microl of
      aqueous MeHgCl and to 8 microl of aqueous solutions containing MeHgCl and MeHgCl
      mixed to fragment 56-61 of metallothionein I (MT I), MT I and MT II-Zn,
      respectively, revealed that all the MTs tested were able to reduce or to inhibit
      the reactions, demonstrating the effect of the thiol groups. Due to the close
      chemical similarities to EtHgCl and to its water solubility, MeHgCl seems to be a
      suitable model for evaluating the reactivity of alkylmercury compounds in the
      skin. We speculate that both EtHg- and MeHg-derivatives are xenobiotics with
      similar reactivity. However, the lack of clinical relevance of the reactions to
      both alkyl compounds lead us to conclude that, since environmental exposure does
      not seem to play a pivotal role, they probably have mostly to do with compounds
      included in in the standard series, and are elicited by reduced function of
      physiological SH chelators.

PMID- 9928799
TI  - The association between size of test chamber and patch test reaction: a
      statistical reanalysis.
AB  - A recent study by Brasch and co-workers reported on the association between size
      of test chamber and patch test reaction. The investigators interpreted their data
      on 495 patients as having conclusively shown that standard preparations of
      fragrance mix, wool wax alcohols, Kathon CG and formaldehyde led to more positive
      test reactions when large Finn Chambers were used for patch testing. We have
      scrutinized the statistical aspects of this study and conclude that the authors
      should have adopted a statistical approach suitable to analyse dependent samples.
      After explaining the correct methodological way of dealing with quadratic
      contingency tables formed by 2 dependent samples, we reanalyze the data
      accordingly and compare the results to those of the original paper. Based on this
      reanalysis, the conclusions are more complex: the reaction pattern for the
      fragrance mix and wool wax alcohols is significantly different between small and
      large test chambers; however, this discrepancy arises primarily from changing
      weak positive reactions with small chambers to strong positive reactions with
      large chambers. For formaldehyde, no relationship between chamber size and patch
      test reaction was found in the data, while for Kathon CG, statistical evidence is
      borderline that more positive test reactions are yielded by large test chambers
      than by small ones.

PMID- 9928800
TI  - Structure-activity relationships in allergic contact dermatitis induced by
      methacrylates. Studies of the influence of side-chain length of methacrylates.
AB  - Some methacrylates are known to be strong contact sensitizers. To determine the
      effect of side-chain length on sensitizing potential, we examined 11 derivatives
      with linear side chains from C1 to C18 in an experimental sensitization test in
      guinea pigs. The results showed an increase in the sensitizing potential with
      increasing length of the alkyl side chain from C1 to C12. The C12 derivative,
      lauryl methacrylate, showed the strongest sensitizing potential. Further
      elongation of the alkyl side chain of methacrylates resulted in a decrease in the
      potential. With respect to the side-chain-length-dependent sensitizing potential,
      the present results correspond well with the findings obtained with other
      compounds like primin, catechols, phenols, hydroquinones, and gallates.

PMID- 9928801
TI  - Patch testing with budesonide in serial dilutions: the significance of dose,
      occlusion time and reading time.
AB  - Budesonide is advocated as a marker molecule for corticosteroid contact allergy.
      When patch testing corticosteroids, one must consider their sensitizing potential
      but also their anti-inflammatory properties, as well as the possibility of
      different time courses for such properties. The dose-response relationship for
      budesonide was therefore investigated with regard to dose, occlusion time, and
      reading time. 10 patients were patch tested with budesonide in ethanol in serial
      dilutions from 2.0% down to 0.0002% with occlusion times of 48, 24, and 5 h.
      Readings were on D2, D4, and D7. The 48-h occlusion picked up most positive
      reactors, 8/10. The D4 reading (48-h occlusion) detected most positive reactors,
      8/10, and here 0.002% picked up most contact allergies. Late readings favoured
      high concentrations. The "edge effect" was noted for several concentrations at
      early readings. Due to the individual corticosteroid reactivity, the dose
      response relationship and the time courses of the elicitation and the anti
      inflammatory capacity, several features may be explained, i.e., that lower
      concentrations may detect budesonide allergy better at early readings, that
      patients with an "edge reaction" can have positive reactions to lower
      concentrations.

PMID- 9928802
TI  - Influence of patch-test application tape on reactions to sodium dodecyl sulfate.
AB  - There remains much room for improvement in the accuracy of the patch test
      procedure. There has been a lack of knowledge regarding the possible relationship
      between the intensity of test reactions and the quality of the tape used to apply
      patch tests. Using different brands of tape, patches coated with 2 mg/cm2 sodium
      dodecyl sulfate (SLS) were applied for 24 h to the backs of 10 volunteers. The
      tape specimens varied in terms of manufacture, elasticity, adhesive strength, and
      water permeability. The intensity of patch test reactions, evaluated visually and
      objectively with both the high resolution laser Doppler perfusion imaging
      technique (HR-LDPI) and transepidermal water loss measurements (TEWL), varied
      significantly with the different brands of tape. Observed variations in the
      intensity of reactions to the patch tests could not be explained by any of the 4
      tape parameters investigated. In order to attain optimal test quality in the
      future, both the tape and patches used in the testing system should be
      standardized and clearly labelled.

PMID- 9928803
TI  - In vitro testing of tensides employing monolayer cultures: a comparison with
      results of patch tests on human volunteers.
AB  - Evaluation of the irritant potential of new products or ingredients prior to
      human testing is generally performed in vivo on animals. However, according to
      the 6th amendment and following updates of the European Community directive on
      cosmetic products (93/35/EEC), animal testing will be banned when suitable
      substitutes will be available. To know whether in vitro tests for assessment of
      skin irritancy provide results approaching human conditions, comparisons have to
      be made between data deriving from in vitro tests and skin response in humans.
      The aim of our study was to assess the validity of the monolayer culture system
      of normal human keratinocytes as a model for the evaluation of the irritant
      effects of detergents, by comparing in vitro cell culture data to in vivo acute
      skin irritancy effects of cocamidopropyl betaine (CAPB), an amphoteric compound,
      Tween 20 (TW20) (polysorbate 20) and Tween 80 (TW80) (polysorbate 80),
      representing nonionic compounds, applied to the skin of 24 healthy volunteers at
      a concentration similar to that employed in commercial products. As parameters
      for cytotoxicity, cell proliferation, cell membrane integrity and cell metabolism
      were assessed by cell counts, thymidine incorporation, MTT conversion, and
      Neutral Red uptake. In order to increase the sensitivity of the in vivo
      evaluation, bioengineering methods for assessment of the effects of test products
      on the skin were employed. Whereas all 4 in vitro methods ranked the tensides
      according to their toxicity in the following order: CAPB>SLS>TW20>TW80, both in
      vivo methods agreed in identifying SLS as the most irritating substance.
      Moreover, as compared with the irritation potential on human skin, all 4 in vitro
      tests overestimated the toxicity of CAPB. This suggests that the keratinocyte
      monolayer cell culture technique cannot directly replace in vivo methods, and
      that data obtained by this method should be interpreted cautiously.

PMID- 9928804
TI  - Clothing dye dermatitis masquerading as (coexisting) mimosa allergy.

PMID- 9928805
TI  - Exposure-pattern dermatitis due to CS gas.

PMID- 9928806
TI  - Contact dermatitis from clotrimazole with positive patch-test reactions also to
      croconazole and itraconazole.

PMID- 9928807
TI  - Contact dermatitis due to diethyl sebacate.

PMID- 9928808
TI  - Contact dermatitis from flavourings in chewing gum.

PMID- 9928810
TI  - Atypical presentation of textile dye sensitization.

PMID- 9928809
TI  - Results of patch testing with dental materials.

PMID- 9928811
TI  - Occupational contact allergy to bisphenol A.

PMID- 9928812
TI  - Fragrance sensitivity in allergic contact dermatitis.

PMID- 9928813
TI  - Sensitization to triglycidyl isocyanurate, epoxy resins and acrylates in a
      developmental chemist.

PMID- 9928814
TI  - A protocol to investigate the blockade of jellyfish nematocysts by topical
      agents.

PMID- 9928815
TI  - Contact allergy due to oil-soluble licorice extracts in cosmetic products.

PMID- 9928816
TI  - Contact dermatitis from para-phenylenediamine used as a skin paint: a further
      case.

PMID- 9928817
TI  - Contact allergy to dibromopropamidine cream.

PMID- 9928818
TI  - Allergic and systemic contact dermatitis from estradiol.

PMID- 9928819
TI  - Nickel dermatitis from coins.

PMID- 9928821
TI  - Reverse relationship between beta-amyloid precursor protein and beta-amyloid
      peptide plaques in Down's syndrome versus sporadic/familial Alzheimer's disease.
AB  - Strong genetic evidence has been accumulated in favor of a central role of beta
      amyloid precursor protein (APP) and beta-amyloid peptide (betaA4) in the
      pathogenesis of Alzheimer's disease (AD). We employed four newly developed APP
      and betaA4 antibodies and performed a comparative neuropathological study of
      patients with Down's syndrome (DS), early-onset familial AD and sporadic AD to
      investigate the distribution of APP and betaA4 plaque densities in the cerebral
      cortex of these disorders. Quantitative analysis of APP versus betaA4 plaques
      revealed that brains with early-onset familial AD and sporadic AD showed
      significantly more betaA4 plaques than brains with DS (P < 0.05). In contrast,
      APP plaques were more abundant in DS cerebral cortex (P < 0.02). These
      observations suggest that the development of pathological changes in DS brains
      does not parallel that observed in AD, which might be attributable to different
      causes in the pathogenesis of betaA4 formation. A comparison of these disorders
      may be useful to further complement our knowledge of the mechanisms leading to
      plaque development.

PMID- 9928820
TI  - A rat model of human T lymphocyte virus type I (HTLV-I) infection: in situ
      detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal
      cords of rats with HTLV-I-induced chronic progressive myeloneuropathy.
AB  - To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I)
      in central nervous system disease, a rat model for HTLV-I-associated
      myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been
      established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I
      infection develop a chronic progressive myeloneuropathy with paraparesis of hind
      limbs after an incubation period of 15 months. In the affected spinal cord in
      these rats, white matter degeneration, demyelination and vacuolar change with
      microglia/macrophage infiltration are present as are the provirus DNA and the
      virus mRNA. To identify infected cells in the affected lesions, we carried out in
      situ hybridization of amplified fragments of the provirus DNA by polymerase chain
      reaction on thin sections, plus immunohistochemistry on the same sections. The
      provirus DNA was localized in some microglia/macrophages in the spinal cord
      lesion. In addition, the HTLV-I provirus was clearly evident not only in ED-1
      negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes.
      These observations suggest that cells of microglia/macrophage lineage may be one
      of dominant viral reservoirs in the spinal cords and lymph nodes in HAM rat
      disease. These infected microglia/macrophages may relate to cause the
      myeloneuropathy through neurotoxic cytokine synthesis.

PMID- 9928822
TI  - Effects of autoantigen and dexamethasone treatment on expression of endothelial
      monocyte activating polypeptide II and allograft-inflammatory factor-1 by
      activated macrophages and microglial cells in lesions of experimental autoimmune
      encephalomyelitis, neuritis and uveitis.
AB  - Endothelial-monocyte activating polypeptide II (EMAP II) and allograft
      inflammatory factor-1 (AIF-1) are two proteins produced by activated monocytes
      and microglial cells. We now report expression of these factors during
      experimental therapy of rat neuroautoimmune diseases. Comparative analysis of two
      therapeutic strategies, treatment with high doses of recombinant autoantigens or
      with dexamethasone, revealed unexpected differences. High doses of autoantigen
      were most effective in experimental autoimmune encephalomyelitis and neuritis
      (EAE and EAN), but less effective in experimental autoimmune uveitis (EAU). Low
      and high doses of dexamethasone treatment greatly reduced the severity of EAE,
      EAN and EAU at day 11, but a relapse was observed between days 21 and 26. Only
      rather limited expression of EMAP II and AIF-1 is seen in the normal central
      nervous system (CNS). This constitutive expression is not abolished by
      dexamethasone treatment. In inflammatory autoimmune lesions of the rat CNS,
      prominent AIF-1 and EMAP II staining was seen with macrophages and monocytes. In
      particular, parenchymal microglial cells were now activated to express AIF-1 and
      EMAP II. In accordance with prevention of neurological signs, histological
      observations revealed that accumulation of activated monocytes expressing EMAP II
      and AIF-1 in the CNS or peripheral nervous system and the massive expression of
      these factors by parenchymal microglial cells is inhibited by high doses of
      autoantigen. Dexamethasone prevented or abolished local expression of EMAP II and
      AIF-1 at days 10-16. However, an acute and severe relapse occurred in
      encephalomyelitis between days 20-26. In these cases, a smoldering expression of
      EMAP II and AIF-1 persisting long after cessation of neurological signs was
      observed. Thus, expression of EMAP II and AIF-1 by infiltrating activated
      macrophages is a marker of disease activity and expression of these factors could
      be used to demonstrate 'silent' lesions in the CNS and prolonged microglial cell
      activation. Apparently, AIF-1 and EMAP II immunoreactivity are tools to stage
      activation of monocytes and microglial cells in inflammatory lesions.

PMID- 9928823
TI  - Development of muscle pathology in canine X-linked muscular dystrophy. I. Delayed
      postnatal maturation of affected and normal muscle as revealed by myosin isoform
      analysis and utrophin expression.
AB  - Canine X-linked muscular dystrophy (CXMD) is genetically homologous to Duchenne
      muscular dystrophy and shares the severe myopathy and lethal clinical development
      of the human disease. We used immunohistochemistry to characterize the time
      course of postnatal expression of adult fast, adult slow and developmental myosin
      in the muscle of CXMD dogs, carriers and healthy controls. We also characterized
      the expression of utrophin and dystrophin. This detailed immunolocalization study
      confirmed that postnatal muscle maturation is delayed in normal dogs compared to
      other animals and humans, and is only achieved at around 60 days. In CXMD dogs
      major derangement of myosin expression became evident from about 15 days; there
      was a selective loss of fibers expressing fast myosin and persistence of
      developmental fibers compared to controls. In carriers, the proportion of
      dystrophin-deficient fibers, which mainly expressed fast myosin, decreased with
      age. In controls and carriers utrophin was absent from muscle fiber surfaces in 2
      day-old animals but present between 15 and 30 days, to mostly disappear by 60
      days. In dystrophic animals, sarcolemmal expression of utrophin was more marked
      and persistent. That immature neonatal muscle from control dogs normally contains
      sarcolemmal utrophin may have implications for the success of utrophin up
      regulation therapy to correct the dystrophic phenotype. The data of this study
      provide important baseline information for further studies on the development and
      progression of pathological changes in the muscle of CXMD dogs.

PMID- 9928825
TI  - Activation of the autophagy, c-FOS and ubiquitin expression, and nucleolar
      alterations in Schwann cells precede demyelination in tellurium-induced
      neuropathy.
AB  - We have used an experimental model of tellurium (Te)-induced demyelinating
      neuropathy in the rat to study cellular mechanisms involved in the early response
      of myelinating Schwann cells (SCs) to injury, prior to demyelination. Starting at
      postnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. The
      animals were killed daily within the 1st week of Te diet and the sciatic nerves
      were processed for the ultrastructural and immunocytochemical studies.
      Immunohistochemistry revealed that Te induces an increased nuclear expression of
      c-Fos in SCs. By electron microscopy analysis, the early cytoplasmic alteration
      was a dramatic disorganization of the rough endoplasmic reticulum (ER) with
      cisternal dilations and redistribution and loss of membrane-bound ribosomes. This
      was followed by a prominent activation of the macroautophagy in SCs. This process
      involved the formation of autophagosomes containing well-preserved cell
      organelles, autolysosomes with cellular remnants in various phases of
      degeneration and lysosomes. Te treatment also induced the expression of free
      ubiquitin in the perikaryal region of the SC cytoplasm. Immunogold electron
      microscopy showed the subcellular distribution of ubiquitin in the cytosol,
      around of dilated ER cisterns and in the matrix of autolysosomes and residual
      bodies. At the nucleolar level, fibrillarin immunofluorescence revealed nucleolar
      segregation in SCs exposed to Te. The ultrastructural study confirmed the
      segregation of the nucleolar components with a peripheral distribution of the
      dense fibrillar component. These results support the hypothesis that the
      depletion of cholesterol induced by Te treatment triggers a stress response in
      myelinating SCs mediated by immediate early genes of the fos family. The cellular
      response includes a severe disruption of the protein synthesis machinery, namely
      the rough ER and nucleolus, with the subsequent activation of both ubiquitin and
      autophagic pathways of proteins and cell organelle degradation. This cytoplasmic
      remodeling may represent a cytoprotective mechanism in the response of SCs to a
      neurotoxic stress. Furthermore, it must be a prerequisite for the induction of
      phenotypic changes and cell repair mechanisms in SCs.

PMID- 9928824
TI  - Markedly different course of Friedreich's ataxia in sib pairs with similar GAA
      repeat expansions in the frataxin gene.
AB  - Friedreich's ataxia (FA) is most frequently caused by intronic trinucleotide
      repeat expansions in the frataxin gene on chromosome 9. The broad clinical
      spectrum includes late-onset FA (LOFA) and FA with retained reflexes (FARR). The
      size of the GAA expansions accounts for most, but not all, of the clinical
      variability. We report the unusual occurrence of LOFA and FARR in two siblings of
      patients with classical early-onset FA in two families. In spite of the markedly
      different course of the disease, the respective siblings harboured GAA repeat
      expansions of similar size in leucocytes. Since haplotype-related variability is
      not likely among siblings, we suppose that this intrafamilial phenotype
      variability is due to somatic mosaicism, with the more severely affected siblings
      harbouring the larger expansions in spinal cord and other affected tissues. In
      view of these results, genetic counseling and predictions on the course of FA are
      particularly difficult, even if an expansion mutation is found.

PMID- 9928827
TI  - No increased incidence of Alzheimer's disease in elderly schizophrenics.
AB  - There is currently controversy as to the morphological basis of cognitive
      impairment in elderly schizophrenics. In contrast to previous findings, recent
      studies have found no increased frequency of Alzheimer's disease (AD) pathology
      in elderly schizophrenics. We examined 99 consecutive autopsy cases of patients
      over the age of 55 years from a psychiatric hospital who met the DSM-III-R and
      ICD.10 criteria for schizophrenia (mean age 69.5 +/- 8.25 years; mean duration of
      illness 35.15 +/- 10.1 years), 56% showing moderate to severe dementia. All
      brains were blindly reviewed for evidence of AD using CERAD criteria and Braak
      staging of neuritic AD lesions. "Definite" AD (CERAD C, Braak stage V) was seen
      in 2 cases aged 56 and 67 years, respectively [2% of total or 1/68 (1.4%) of
      those over age 65]. "Probable" AD (CERAD B, Braak stages IV-V) were seen in 5
      cases aged 71-89 years (mean 79 years; 5% of total or 7.3% of those over age 65),
      and 1 case each with multiple cerebral infarcts and with Parkinson's disease
      pathology. In addition, 2 females aged 82 and 89 years, respectively, revealed
      senile dementia with tangles (NIA, CERAD negative; Braak stage IV), 1 with
      hippocampal sclerosis. The total incidence of definite and probable AD in this
      cohort was 7.1% or 8.7% for those over age 65. This is in line with other recent
      studies showing that the frequency of AD in elderly schizophrenics may be equal
      or even less than in the general population. The reasons for this negative
      association and the basis of cognitive deficits in elderly schizophrenics--those
      with dementia usually showing significantly lower brain weight--await further
      elucidation.

PMID- 9928826
TI  - Entorhinal cortex of aged subjects with Down's syndrome shows severe neuronal
      loss caused by neurofibrillary pathology.
AB  - In Alzheimer's disease (AD), neurofibrillary degeneration of neurons starts in
      the transentorhinal cortex and spreads in a time-dependent manner to the
      entorhinal cortex, which provides a major input to the hippocampus--a key
      structure of the memory system. People with Down's syndrome (DS) develop
      neurofibrillary changes more than 30 years earlier than those with sporadic AD.
      To characterize AD-related pathology in the entorhinal cortex in DS, we examined
      seven subjects with DS of 60-74 years of age who died in the end stage of AD, and
      four age-matched control subjects. The volume of the entorhinal cortex in brains
      of subjects with DS was 42% less than that in control cases; however, the total
      number of neurons free of neurofibrillary changes was reduced in DS by 90%: from
      9,619,000 +/- 914,000 (mean +/- standard deviation) to 932,000 +/- 504,000. The
      presence of 2,488,000 +/- 544,000 neurofibrillary tangles in the entorhinal
      cortex of people with DS, the prevalence of end-stage tangles, and the
      significant negative correlation between the total number of intact neurons and
      the percentage of neurons with neurofibrillary changes indicate that
      neurofibrillary degeneration is a major cause of neuronal loss in the entorhinal
      cortex of people with DS. The relatively low amyloid load (7 +/- 1%) and lack of
      correlation between the amyloid load and the volumetric or neuronal loss suggest
      that the contribution of beta-amyloid to neuronal loss in the entorhinal cortex
      is unsubstantial.

PMID- 9928828
TI  - Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type)
      with non-neuritic amyloid plaque formation.
AB  - The histological features of familial cerebral amyloid angiopathy (British type)
      with non-neuritic amyloid plaque formation (FAB) include deposition of amyloid,
      (supposedly associated with the C-terminal fragments of both alpha- and beta
      tubulin), in small cerebral and spinal arteries, hippocampal amyloid plaques and
      neurofibrillary tangles (NFTs) as well as ischaemic white matter changes. In the
      present study we report on the cytoskeletal pathology that occurs in association
      with FAB. Sections from the hippocampus and cerebellum of three cases from three
      unrelated families were stained with silver impregnation methods and antibodies
      to antigens including tau, neurofilaments, ubiquitin and glial fibrillary acidic
      protein. Electron microscopic examination of the hippocampus was carried out in
      one case. All hippocampal subregions contained large numbers of NFTs and neuropil
      threads (NT), which were stained with both phosphorylation-dependent and
      phosphorylation-independent tau antibodies and ultrastructurally were found to be
      composed of paired helical filaments (PHFs). Although the majority of the amyloid
      plaques were of the non-neuritic type, distended PHF-containing and tau-positive
      neurites were seen in close proximity of a minority of the hippocampal plaques.
      The perivascular amyloid deposits of the cerebellum contained numerous ubiquitin
      positive granular elements similar to those seen in cerebellar A beta amyloid
      plaques in Alzheimer's disease. In FAB severe cytoskeletal pathology is present
      in areas most affected by amyloid plaque deposits, thus suggesting a localised
      neurotoxic effect of the poorly characterised amyloidogenic peptide
      characteristic of this condition.

PMID- 9928829
TI  - Immunohistochemical study of some cytoskeletal proteins in hereditary myopathy of
      the diaphragmatic muscles in Holstein-Friesian cattle.
AB  - We have investigated the expression, using immunohistochemical and Western blot
      methods, of some cytoskeletal proteins including desmin, vimentin, actin, alpha
      actinin, and ubiquitin in hereditary myopathy of the diaphragmatic muscles in
      Holstein-Friesian cattle (the histochemical and electron microscopical aspects
      have been previously reported). Immunohistochemically, the expression of desmin
      was observed strongly in the subsarcolemmal regions, but was lacking or faint in
      the area corresponding to the core-like structures. Vimentin showed almost the
      same localization as desmin, but no activity could be observed in the core-like
      structures. In addition, the core-like structures showed strong immunoreactivity
      for actin and ubiquitin, but no immunoreactivity for alpha-actinin. F-actin
      stained with phalloidin-tetramethyl-rhodamine was strongly positive in irregular
      spots that corresponded to the core-like structures, but was negative for desmin
      positive regions. Western blot analysis of the diseased muscles revealed a
      significant increase in the amount of desmin and vimentin immunoreactivities and
      similar amounts of actin and alpha-actinin compared with the control muscles. Two
      dimensional electrophoresis revealed no isoforms of desmin, suggesting the
      absence of abnormal phosphorylated forms of desmin. Since the co-localization of
      desmin and vimentin and the absence of phosphorylated desmin suggest that the
      overexpression of desmin may be reflected in the reactive change or regenerating
      process, the present myopathy should be regarded as an entity separate from
      desmin-storage myopathy or desmin-related myopathies. We also discuss the
      possibility that the present myopathy could be considered as myofibrillar
      myopathy, a recently proposed nosological entity.

PMID- 9928830
TI  - Immunohistochemical and electron microscopical studies of myocardial inclusions
      in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle.
AB  - In hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle,
      the largest number of acidophilic intracytoplasmic inclusions was found in the
      myocardium. These inclusions, which were oval and measured 12-15 microm in the
      transverse sections, were characterized by a dense, amorphous zone, and a
      relatively hyalinized sarcous substance in paraffin-embedded hematoxylin and
      eosin (H & E)-stained sections. Histochemically, each inclusion was stained
      intense red and dark green with H & E and Gomori's trichrome, respectively. NADH
      TR activity was absent. The region surrounding the inclusions was less
      acidophilic with H & E, and showed an increased activity with NADH-TR. The
      inclusions showed no immunoreactivity for desmin, vimentin, actin or alpha
      actinin, while strong desmin immunoreactivity was observed in the region
      surrounding the inclusion. Some inclusions showed strong immunoreactivity for
      ubiquitin, but others reacted only faintly. Ultrastructurally, the inclusion had
      a dense core composed of myofibrillar aggregations. The periphery of this dense
      core was surrounded by thin or intermediate-sized filaments, which corresponded
      to the desmin-positive area. This alteration was sometimes found to be continuous
      with the Z disk, which showed streaming or disintegration or with the desmosome
      of the intercalated disk. We discuss here the similarity between this specific
      inclusion and the other alternative organelles that have been reported previously
      in cardiomyopathy or in cardiac lesions associated with various myopathies.

PMID- 9928831
TI  - Neuronal vacuolation in young Rottweiler dogs.
AB  - Neuronal vacuolation, involving the cerebellar roof nuclei, Purkinje cells,
      selected nuclei of the brain stem, thalamus, Clarke's column, anterior and
      posterior horns of the spinal cord, visceral autonomic ganglia and myenteric
      plexus, as well as axonal degeneration of the white matter of the brain stem,
      cerebellar pedunculi, dorsolateral columns of the spinal cord and ventral roots
      of the spinal cord, were observed in two young Rottweiler dogs which were
      clinically afflicted with hind limb weakness progressing to paraparesia, ataxia,
      intention tremor, and difficulty in swallowing and barking. The absence of
      modifications in Bcl-2 and Bax immunoreactivity, a lack of strong c-Jun/AP-1 (N)
      immunoreactivity in vacuolated cells, and the absence of DNA breaks, as seen with
      the method of in situ end-labeling of nuclear DNA fragmentation, all suggest that
      there is no involvement of the apoptotic pathway in vacuolated cells in this new
      neurodegenerative disorder.

PMID- 9928832
TI  - An immunohistochemical study of Purkinje cells in a case of hereditary cerebellar
      cortical atrophy.
AB  - We report an immunohistochemical study of Purkinje cells located in the molecular
      layer (ectopic Purkinje cells) and in the Purkinje cell layer (orthotopic
      Purkinje cells) of a patient who died young and had been diagnosed with
      hereditary cerebellar cortical atrophy from both clinical and neuropathological
      findings. All the ectopic and orthotopic Purkinje cells were immunoreactive with
      an anti-calbindin-D antibody, confirming that these stained cells were Purkinje
      cells. The perikarya of some ectopic and orthotopic Purkinje cells were stained
      by an antibody to phosphorylated neurofilament. In contrast, Purkinje cells of
      three normal controls did not react with this antibody. This finding of an
      abnormal accumulation of phosphorylated neurofilaments in the perikarya may be
      due to abnormal phosphorylation. Moreover, the regions around the cell bodies of
      some ectopic and orthotopic Purkinje cells were intensely immunoreactive with an
      antibody to synaptophysin, which suggests an abnormal increase in presynaptic
      terminals. It is suggested that ectopia of Purkinje cells, accumulation of
      phosphorylated neurofilament in the perikarya and an abnormal increase in
      presynaptic terminals around the soma of the Purkinje cells may be relevant to
      the pathophysiology of Purkinje cell degeneration in this case. In addition, the
      relationship between phosphorylated neurofilament and synaptophysin reactivity is
      discussed.

PMID- 9928833
TI  - Nuclear inclusions in spinocerebellar ataxia type 1.
AB  - Spinocerebellar ataxia type 1 is due to a CAG repeat expansion in the gene
      encoding ataxin-1. In a case with an expansion of 56 repeats, intranuclear
      inclusions were found only in neurons, both in severely affected regions (such as
      the pons) and in areas where the lesions were inconspicuous (such as the cortex
      or the striatum). The inclusions were labelled by a monoclonal antibody directed
      against long polyglutamine stretches (1C2); they were also detected by the anti
      ubiquitin antibody. They were faintly eosinophilic, Congo red negative and were
      not stained by thioflavin S or by ethidium bromide.

PMID- 9928834
TI  - Can secondary degeneration accelerate the formation of neurofibrillary tangles? A
      case of hemispheric infarction showing asymmetric degeneration of the substantia
      nigra, red nuclei, inferior olivary nuclei and dentate nuclei with concomitant
      changes of progressive supranuclear palsy.
AB  - A case of hemispheric infarction involving the territory of the right middle
      cerebral artery and the thalamus showed conspicuous asymmetric degeneration in
      the substantia nigra, red nuclei, inferior olivary nuclei and dentate nuclei with
      concomitant changes of progressive supranuclear palsy (PSP). The right substantia
      nigra and red nucleus showed loss of neurons and proliferation of astrocytes. The
      right olivary nucleus was hypertrophic, while the neuronal loss and astrocytosis
      in the dentate nucleus were predominant on the contralateral side. Modified
      Gallyas-Braak staining revealed the extensive distribution of neurofibrillary
      tangles (NFTs), threads and intraglial argyrophilic structures in the globus
      pallidus, subthalamic nuclei, cerebral cortex and dentate nuclei, as well as in
      the affected brain stem nuclei, with a distinct predominance on the affected
      side. In this case, the one-sided predominance of the extended degeneration in
      these brain stem and cerebellar areas is considered, in addition to the PSP
      changes, to be due to secondary retrograde degeneration via the nigrostriatal and
      dentato-rubro-thalamic pathways following the hemispheric infarction, and to also
      be the result of disruption of the dentato-olivary fiber connections. In
      addition, because of the predominant distribution of NFTs on the more degenerated
      side, it is surmised that the formation of NFTs may be accelerated by secondary
      degeneration.

PMID- 9928835
TI  - Lateral balance organisation in human stance in response to a random or
      predictable perturbation.
AB  - The effect of the predictability of perturbation to standing balance was
      evaluated in terms of the muscle activity and response dynamics of five subjects
      exposed to horizontal forces at the pelvis producing sideways or forward sway.
      Rapid (EMG onset latencies of 70-80 ms recorded from the left gluteus medius and
      gastrocnemius) and qualitatively different patterns of response were produced by
      forward pushes and pushes to either side. However, the EMG response to left push
      was constant in pattern and timing, whether the push direction was constant and,
      therefore, predictable over a block of trials or whether the left push trials
      were interleaved randomly with right push or forward push trials. Moreover, there
      were no systematic effects of perturbation direction uncertainty on the latency
      and rate of increase of ground reaction forces. We conclude that prior
      information does not speed postural responses that differ quantitatively
      according to the direction of perturbation to balance.

PMID- 9928836
TI  - Estimation of PC12 cell numbers with acid phosphatase assay and mitochondrial
      dehydrogenase assay: dopamine interferes with assay based on tetrazolium.
AB  - Both the acid-phosphatase and mitochondrial dehydrogenase assay have been used to
      quantify cell numbers. The commonly used acid-phosphatase assay uses p
      nitrophenyl phosphate as a substrate, while the mitochondrial dehydrogenase assay
      is based on the conversion of tetrazolium to formazan. Our experimental results
      showed that the former assay was more sensitive in detecting small numbers of
      PC12 cells (200-10,000 cells/well), whereas the latter was useful for larger
      numbers of cells (2000-40,000 cells/well). The number of PC12 cells decreased
      after dopamine treatment, according to the acid-phosphatase assay and by direct
      cell counts under a light microscope. However, the optical densities measured by
      the mitochondrial dehydrogenase assay increased after dopamine treatment. We
      tried to clarify discrepancies between the two assays, since dopamine is an
      important neurotransmitter and both assays are commonly used to estimate cell
      numbers. To elucidate the interference between dopamine and tetrazolium salt,
      cell-free control experiments were performed. Dopamine and other catecholamines
      (adrenaline and noradrenaline) reacted with tetrazolium and, thus, produced a
      false positive reaction in the assay. We therefore conclude that the tetrazolium
      assay is not a suitable method for evaluating the number of catecholamine-treated
      cells, while the acid-phosphatase assay is reliable and sensitive.

PMID- 9928837
TI  - The effect of target size and inertial load on the control of rapid aiming
      movements. A test of speed-sensitive and speed-insensitive strategies.
AB  - Two experiments are reported that investigated the effects of target size and
      inertial load on the control of rapid aiming movements. Based on kinematic
      profiles, movements were partitioned into their preprogrammed initial impulse-
      and feedback-based error correction phases. Electromyographic (EMG) rise rates
      were examined to investigate whether participants used a speed-sensitive or speed
      insensitive control strategy. The results from both experiments showed that
      initial impulse velocity and EMG rise rates varied as a function of target size,
      i.e., a speed-sensitive strategy. This was the case whether participants were
      allowed to make error corrections to their movements (experiment 1) or were
      instructed to produce initial impulses that hit the target (experiment 2). Both
      experiments also showed that initial impulse velocity and endpoint variability
      were inversely related to inertial load. The results from experiment 2 indicated
      that, while the manipulation of inertial load had no effect on EMG rise rates for
      movements to a large target, EMG slopes were modulated between inertial load
      conditions when the target was small.

PMID- 9928838
TI  - Neck muscle activity after unilateral labyrinthectomy in the alert guinea pig.
AB  - In the guinea pig, lateral deviation of the head is a cardinal symptom of the
      vestibular syndrome caused by unilateral labyrinthectomy. In the course of
      recovery from this syndrome (vestibular compensation), lateral deviation of the
      head disappears completely in 2-3 days. Because this symptom is known to be due
      to the lesion of the horizontal semicircular canal system, and since obliquus
      capitis inferior (OCI) muscle is activated predominantly by yaw rotation
      (horizontal vestibulocollic reflex), we hypothesized that changes in the activity
      of this muscle could be at least in part responsible for the lateral head
      deviation caused by unilateral labyrinthectomy. In order to test this hypothesis,
      electromyographic (EMG) activities of the right and left OCI muscles, as well as
      eye movements, were recorded in 12 head-fixed alert guinea pigs at various times
      after left surgical labyrinthectomy (performed with the animals under halothane
      anesthesia). After the operation, a decrease in tonic EMG activity was observed
      in the right (contralateral to the lesion) OCI muscle while an increase in tonic
      EMG activity was detected in the left (ipsilateral) OCI muscle. In addition,
      phasic changes in EMG activity associated with ocular nystagmic beats occurred in
      the OCI muscles. These phasic changes were in the opposite direction to those of
      the tonic changes. There were bursts of activity in the right OCI and pauses in
      the left OCI. From measurements of rectified averaged EMG activities which took
      into account both parts (tonic and phasic) of the phenomenon, it was concluded
      that the labyrinthectomy-induced asymmetry between the activities of the left and
      right OCI muscles was high enough and lasted long enough to be an important
      mechanism in the lateral deviation of the head caused by unilateral
      labyrinthectomy.

PMID- 9928839
TI  - Vibration sensitivity of cat muscle spindles at short muscle lengths.
AB  - Experiments are described in which the vibration sensitivity was tested for
      primary and secondary endings of soleus muscle spindles of the anaesthetised cat.
      The vibratory stimulus was applied longitudinally to the muscle tendon and, after
      locating the site of the spindle in the muscle, applied transversely to muscle
      fibres directly overlying the spindle. All measurements were made with the muscle
      slack, at 20 mm shorter than its maximum physiological length (Lm-20 mm).
      Spindles were separated into two groups: spontaneous spindles, which maintained
      background activity at this length, and silent spindles, which did not. Two forms
      of muscle conditioning were used: hold-long, in which the muscle was stretched by
      5 mm, contracted and then returned to the test length, and hold-test, in which a
      conditioning contraction was given at the test length. After hold-test, most
      spindles responded to longitudinal vibration; after hold-long, most did not. This
      difference in responsiveness was attributed to the presence or absence of slack
      in intrafusal and extrafusal fibres, due to the muscle's thixotropic property.
      When the vibration was applied transversely, at a site directly overlying the
      spindle, responses of silent spindles continued to show thixotropic behaviour,
      whereas responses of spontaneous spindles were almost independent of the form of
      muscle conditioning. It is proposed that the ability of spontaneous spindles to
      maintain background activity at short muscle lengths is due to connective tissue
      or elastic fibre links between the sensory ending and the spindle capsule. The
      vibratory stimulus, applied transversely, reaches the sensory ending via these
      strands which, as non-muscle tissue, do not alter their mechanical state as a
      result of muscle conditioning.

PMID- 9928840
TI  - Botzinger-complex, bulbospinal expiratory neurones monosynaptically inhibit
      ventral-group respiratory neurones in the decerebrate rat.
AB  - Extracellularly recorded action potentials from 49 Botzinger-complex, bulbospinal
      expiratory neurones were used as triggers to compute 162 spike-triggered averages
      (STAs) of intracellular potentials recorded from 167 respiratory neurones in the
      ventral respiratory group (VRG) near the obex in 15 vagotomized, paralysed,
      ventilated and decerebrated rats. All of the Botzinger-complex expiratory
      neurones were antidromically activated from the ipsilateral border between the
      C2/C3 segments of the spinal cord and discharged only during the late part of
      expiration with an augmenting pattern. We found evidence for monosynaptic
      inhibitory post-synaptic potentials (IPSPs) in 74 (approximately 44%) of the STAs
      computed using 34 (approximately 69%) of the trigger neurones. For vagal
      motoneurones, IPSPs were found in 24 of the 53 STAs of expiratory motoneurones,
      but in none of the 12 STAs of inspiratory motoneurones. For inspiratory neurones,
      IPSPs were found in 23 of the 33 STAs of bulbospinal neurones and in 6 of the 26
      STAs of not antidromically activated (NAA) neurones. For expiratory neurones,
      IPSPs were found in one of the two STAs of bulbospinal neurones and in 20 of the
      36 STAs of NAA neurones. We conclude that Botzinger-complex, bulbospinal
      expiratory neurones monosynaptically inhibit bulbospinal inspiratory neurones,
      expiratory vagal motoneurones and other unidentified inspiratory and expiratory
      neurones in the VRG of rats during the late part of expiration.

PMID- 9928841
TI  - Binocular interactions and spatial disparity sensitivity in the superior
      colliculus of the Siamese cat.
AB  - In Siamese cats, a genetically determined massive misrouting of retinal ganglion
      cells toward the contralateral hemisphere, as well as an accompanying strabismus,
      is believed to underlie the extreme paucity of binocular cells in the primary
      visual cortex. However, binocular cells have been shown to be present in more
      important numbers at the collicular level. The present study aims at
      investigating binocular interactions and sensitivity to spatial disparity in the
      superior colliculus of the Siamese cat. The activity of single units was recorded
      in the superficial layers of paralyzed and anesthetized Siamese cats. Although
      most collicular cells were monocularly driven, a significant proportion could be
      driven through both eyes (34/216 or 16%). Upon isolation of a binocular cell, the
      receptive fields were separated, then simultaneously stimulated with two light
      bars. A temporal delay was introduced between the arrival of the bars in the
      receptive fields to generate spatial disparities (-3 degrees to +3 degrees, in
      0.5 degrees or 1 degree steps). Results showed that some binocular cells
      presented disparity tuning profiles similar to the tuned excitatory (12/34),
      tuned inhibitory (2/34), near (2/34) and far (3/34) cells found at various
      cortical levels in the normal cat. These interactions might allow for coarse
      binocular fusion as well as play a role in the initiation of vergence and the
      fixation of the eyes upon the appropriate plane of vision.

PMID- 9928842
TI  - Chloride channels activated by hypotonicity in N2A neuroblastoma cell line.
AB  - By using the patch-clamp technique we have shown that, in hypotonic extracellular
      solutions, the mouse neuroblastoma cells Neuro2A (N2A) develop ionic currents
      mediated by a chloride-selective channel which is also permeable to other anions
      in accordance with the permeability sequence: I->Br->Cl->gluconate->glutamate-.
      The currents persist for several hours when Mg-ATP is present in the recording
      pipette but occur only transiently in the absence of Mg-ATP. Typical blockers of
      anions channels such as La3+ and Zn2+ do not affect the hypotonicity-activated
      channel; conversely, the stilbene sulfonate-derivatives, 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), reversibly inhibit the
      channel in a voltage-dependent manner. Also intact cells exposed to hyposmotic
      solutions activate volume-regulation mechanisms which decrease the transient
      volume increase that develops immediately after the application of the hyposmotic
      challenge. Since N2A neurons have been used as an expression system of exogenous
      channels, the presence of osmolarity-regulated channels in these cells is an
      important aspect that deserves the attention of researchers who may wish to
      express and study the properties of transport proteins in this cell line.

PMID- 9928843
TI  - Planning dysfunction in schizophrenia: impairment of potentials preceding
      fixed/free and single/sequence of self-initiated finger movements.
AB  - To test the hypothesis of a planning dysfunction in schizophrenia using a precise
      temporal definition, the readiness potential (RP), a negative cortical wave
      preceding self-initiated movements and reflecting motor preparation processes,
      was studied in patients under stable medication and in controls. The
      supplementary motor area (SMA), known to be involved in the generation of the RP,
      has also been implicated in movement selection (fixed versus free) and complexity
      (single versus sequence). This is the first study using RP for the assessment of
      the influence of these factors on motor preparation in schizophrenics. Our
      results show that schizophrenics' RP amplitude is significantly lower than in
      controls at central and contralateral electrodes. However, RP amplitude increases
      with task difficulty in both groups, offering important new insight into
      classical SMA hypoactivation in schizophrenics performing motor tasks.
      Topographic analysis shows that RP amplitude is, for both groups, significantly
      higher in sequence than in single movements at fronto-central sites and higher
      for free than for fixed movements at centro-parietal sites. Finally, RP onset
      occurs significantly later in schizophrenics than in controls. These results
      support the view of a motor-preparation and decision-making dysfunction in
      schizophrenia. They are interpreted within the framework of a fronto-striatal
      disorder in this disease.

PMID- 9928844
TI  - Kainic acid-induced activation of nuclear factor-kappaB in rat hippocampus.
AB  - Nuclear factor-kappaB (NF-kappaB) is known to play a key role in immune and
      inflammatory responses. To understand the mechanisms of inflammatory activation
      that accompany neuronal damage, we determined the cell type in which NF-kappaB
      was activated. NF-kappaB protein was detected in the cytosolic fraction of
      untreated and vehicle-treated rat hippocampus. After kainic acid (KA) treatment,
      NF-kappaB protein was significantly increased in both the cytosolic and
      particulate fractions. NF-kappaB immunoreactivity was observed in both brain
      blood vessels and glial cells after 1 day. Although NF-kappaB immunoreactivity in
      brain blood vessels disappeared after 3 days, this activity was maintained in
      glial cells for up to 7 days. In addition, double immunostaining indicates that
      NF-kappaB was activated in glial cells, such as microglia and astrocytes, after 3
      days. Thus, NF-kappaB activation seems to be delayed and to occur continuously in
      microglia and astrocytes, suggesting that an inflammatory activation in glial
      cells participates in KA-induced neurodegeneration.

PMID- 9928845
TI  - The thought translation device: a neurophysiological approach to communication in
      total motor paralysis.
AB  - A thought translation device (TTD) for brain-computer communication is described.
      Three patients diagnosed with amyotrophic lateral sclerosis (ALS), with total
      motor paralysis, were trained for several months. In order to enable such
      patients to communicate without any motor activity, a technique was developed
      where subjects learn to control their slow cortical potentials (SCP) in a 2-s
      rhythm, producing either cortical negativity or positivity according to the task
      requirement. SCP differences between a baseline interval and an active control
      interval are transformed into vertical or horizontal cursor movements on a
      computer screen. Learning SCP self regulation followed an operant-conditioning
      paradigm with individualized shaping procedures. After prolonged training over
      more than 100 sessions, all patients achieved self-control, leading to a 70-80%
      accuracy for two patients. The learned cortical skill enabled the patients to
      select letters or words in a language-supporting program (LSP) developed for
      inter-personal communication. The results demonstrate that the fast and stable
      SCP self-control can be achieved with operant training and without mediation of
      any muscle activity. The acquired skill allows communication even in total locked
      in states.

PMID- 9928846
TI  - Age-dependence of the lateral diffusion coefficient of concanavalin-A receptors
      in the plasma membrane of ex vivo prepared brain cortical nerve cells of
      BN/BiRijHsd rats.
AB  - A new method has been developed for ex vivo preparation of brain cortical cells
      of BN/BiRijHsd rats to make them suitable for the measurement of the lateral
      diffusion coefficient of the membrane components by means of fluorescence
      recovery after photobleaching (FRAP). The method involves chopping the brain
      cortex into pieces of less than 1 mm. These parts are stained with a fluorescent
      label (e.g., concanavalin-A-fluorescein, Con-A-FL conjugate) and then gently
      pressed onto a microscope slide using the coverslip. In the resulting specimen,
      the largest cells of the cortex can be recognized in phase-contrast image,
      sufficiently stained by the label and ready for the FRAP measurement. The lateral
      diffusion coefficient of Con-A-receptor proteins (Dp) was measured in such brain
      cell preparations of 15 female rats in four age groups (5.6-31.8 months) and 11
      males in three age groups (13.8-31.8 months). Highly significant negative, linear
      age correlation of Dp (R=-0.9958 in females, and -0.9956 in males) were found,
      the regression equations being D(p female) =(8.8311-0.1425 X)(-10) and D(p
      male)=(9.3240-0.1630 X)(-10) cm2/s, respectively, where X is age in months. The
      data confirm that the lateral mobility of plasma membrane proteins represents an
      important biomarker of cellular aging in the brain cortical cells of BN/BiRijHsd
      rats.

PMID- 9928847
TI  - The antioxidant melatonin reduces cortical neuronal death after intrastriatal
      injection of kainate in the rat.
AB  - The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in
      kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol
      in 1 microl) was directly injected to unilateral striatum. Melatonin (10 mg/kg)
      was administrated intraperitoneally 1 h before and 1, 3, and 5 h after
      intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after
      kainate injection, a significant neuronal damage was found, as determined by
      Nissl staining and the TUNEL method, not only in the injected striatum, but also
      in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic
      neuronal death was significantly attenuated by treatment with melatonin compared
      with the vehicle control group. However, no detectable changes were observed in
      the contralateral side of the brain in either vehicle- or melatonin-treated rats.
      Moreover, the biochemical results indicated that kainate can indeed induce
      oxidative stress, such as a decrease in the content of total glutathione (GSH),
      oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the
      striatum and cortex compared with the contralateral brain regions. In the kainate
      injected striatum, melatonin did not reduce the oxidative stress, but in the
      neighborhood of injected area-cortex, kainate-induced oxidative stress was
      significantly reduced by melatonin. Enhancement of glutathione-peroxidase
      activity was induced by intrastriatal kainate injection, not only in the cortical
      area of control and melatonin-treated rats, but also in striatum of control rats.
      However, a large elevation was found in the melatonin-treated cortex. Taking the
      morphological and biochemical data together, the present results suggest that
      melatonin functions as an antioxidant by upregulating the glutathione
      antioxidative defense system, thereby reducing neuronal death caused by
      excitotoxicity and preventing the kainate-induced damage from spreading to
      adjacent brain regions.

PMID- 9928848
TI  - Differences in mossy and climbing afferent sources between flocculus and ventral
      and dorsal paraflocculus in the rat.
AB  - Sources of mossy and climbing fiber inputs to the flocculus (FL), ventral
      paraflocculus (VP) and/or dorsal paraflocculus (DP) were identified in the
      vestibular ganglion, medulla oblongata and pons of 19 Wistar rats after 26 local
      injections of horseradish peroxidase, wheat-germ agglutinin-conjugated
      horseradish peroxidase, fast blue or diamidino yellow into the FL, VP and/or DP.
      There were large differences in the sources of mossy fibers to the FL and VP/DP.
      Labeled neurons after injections into the FL were observed mainly in the
      ipsilateral vestibular ganglion, bilaterally in the vestibular and prepositus
      hypoglossal nuclei, and in the caudal part of the nucleus reticularis tegmenti
      pontis. Labeled neurons were rarely observed in the pontine nuclei after
      localized injections into the FL. By contrast, after injections into the VP
      and/or DP, numerous labeled neurons were observed in the pontine nuclei with a
      contralateral predominance and in the rostral part of the nucleus reticularis
      tegmenti pontis bilaterally, but not in the vestibular nuclei in either side.
      Sources of climbing fibers to the FL and paraflocculus were completely
      contralateral to the injection side. After injection into the FL, labeled neurons
      were observed in the caudal dorsal cap and ventrolateral outgrowth of the
      inferior olivary nucleus. After injections into the VP, labeled neurons were
      observed mainly in the rostral dorsal cap, ventral medial accessory olivary
      nucleus (MAO) and caudal half of the ventral leaf of the principal olivary
      nucleus. After injections into the DP, labeled neurons were observed in the
      ventral MAO and caudal half of the ventral leaf of the principal olivary nucleus.
      These differences in the sources of mossy and climbing fiber inputs may suggest
      functional differences between the FL and VP/DP. The present results are
      consistent with our previous observations in monkey that the FL and VP/DP exhibit
      quite different mossy fiber input organizations.

PMID- 9928849
TI  - Amplitude of the maximum motor response (Mmax) in human muscles typically
      decreases during the course of an experiment.
AB  - It was shown that the amplitude of the soleus Mmax and Hmax responses decreases
      in the course of long-lasting H-reflex studies. The peak-to-peak amplitudes of
      the Mmax and Hmax responses in the soleus muscle (and the Mmax in the tibialis
      anterior muscle and small hand muscles) were measured repeatedly for 1-3 h in 20
      subjects. 3-5 Mmax responses and 5-10 Hmax responses were elicited about every 3
      min while the subject was at rest. Decreases in the soleus Mmax response of up to
      50.5% (mean 20.5% SEM 2.2) and of the soleus Hmax of up to 49.7% (mean 19.1% SEM
      3.7) in relation to the amplitudes measured at the beginning of the experiment
      were seen in 17 subjects. In 3 subjects no Mmax amplitude decrease was seen. The
      maximum decrease was reached between 10 and 100 min (mean 44.2 min SEM 4.3). An
      Mmax amplitude decrease was also seen in the tibialis anterior muscle and in two
      small hand muscles. In some subjects the decrease of the Mmax response seemed to
      be initiated by the infrequent supramaximal stimulations. The possible causes for
      this amplitude reduction, as well as the methodological consequences of these
      findings for H-reflex studies and fatigue studies, are briefly discussed.

PMID- 9928850
TI  - N-tert-butyl-alpha-phenylnitrone reduces the number of microinfarctions in the
      rabbit brain cortex.
AB  - Dementia due to cerebral ischemic lesions is relatively common in the elderly.
      Since many of these lesions are probably caused by emboli, studying emboli
      induced cerebral lesions in rabbits should, hopefully, provide information that
      is useful when searching for a means of preventing and treating vascular dementia
      in humans. Using magnetic resonance imaging we have found that N-tert-butyl-alpha
      phenyl-nitrone (a free radical scavenger) reduced the number of emboli-induced
      cerebral microinfarctions in the rabbit cortex but did not have any impact on the
      number of infarctions found in the subcortical structures. The results suggest
      that significant amount of free radicals are produced in the ischemic foci
      located in the cortex, but not in the ischemic foci located in the subcortical
      structures. This finding may be of importance when considering treatments for
      cerebral ischemia in humans.

PMID- 9928851
TI  - Internal atrial defibrillation - a new treatment of postoperative atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) commonly occurs following open heart surgery
      and may delay hospital discharge. Transthoracic electrical cardioversion is used
      when medical treatment is ineffective or associated with side effects.
      Traditionally general anesthesia is required. The aim of this multicenter study
      was to examine the feasibility and efficacy of low-energy atrial defibrillation
      using temporary epicardial defibrillation wire electrodes. METHODS: Epicardial
      stainless-steel defibrillation wire electrodes were sutured onto the left and
      right atrium during open heart surgery in 238 patients (age 64+/-9 years; 180
      males). In case of postoperative AF R-wave synchronous low-energy shocks (0.6
      10.8J) were applied to achieve cardioversion without anesthesia. RESULTS:
      Implantation of the electrodes added 4.3+/-2.8 minutes to the operating time.
      During the hospital stay AF occurred in 47 patients (20%) at 2.1+/-1.3 days
      postoperatively. Fifty-one episodes of AF occurring in 44 patients were treated
      by atrial defibrillation. Primary success rate of cardioversion was 33/51 (65%).
      Early recurrence of AF (within 60 seconds after defibrillation) developed in 15
      patients. Seven of these 15 patients were successfully defibrillated later on.
      Overall success rate was 40/51 (78%). The mean energy of successful shocks was
      5.8+/-2.7 J. A mean of 2.3+/-1.7 shocks were applied per patient. The shocks were
      well tolerated by the patients in the absence of anesthesia. No complications
      were observed with shock application or with lead extraction. CONCLUSION: Atrial
      defibrillation using temporary epicardial wire electrodes can be performed safely
      and effectively in patients following cardiac surgery. The shock energy required
      to restore sinus rhythm is low.

PMID- 9928852
TI  - Changes of leukocyte subsets in coronary artery bypass surgery: cardiopulmonary
      bypass versus 'off-pump' techniques.
AB  - BACKGROUND: The use of cardiopulmonary bypass (CPB) in coronary bypass grafting
      is associated with a generalized inflammatory response. This negative impact of
      CPB may be avoided by using new surgical techniques recently introduced to
      perform coronary bypass grafting 'off-pump', i.e. without CPB. METHODS: Since the
      specific effects of CPB on the immunorelevant cells have still not been fully
      investigated, we measured the changes in leukocyte subsets of the circulating
      blood in patients who underwent coronary bypass surgery with a conventional
      sternotomy approach and CPB (group A, n = 10), in patients who underwent the same
      surgical procedure but without CPB (group B, n = 10), and in patients who
      underwent a minimally invasively performed single bypass to the left anterior
      descending artery (LAD) (group C, n = 10). RESULTS: Leukocyte subsets showed a
      similar change during and after coronary bypass grafting in all three groups. The
      total number of leukocytes was increased soon after reperfusion in the CPB group.
      A similar but delayed increase was observed in both off-pump groups. Changes in
      lymphocyte subsets and T-lymphocyte subsets were similar in all three groups,
      with a drop of lymphocytes during the first 24 postoperative hours mainly caused
      by a drop of T4-helper cells. CONCLUSION: The results indicate a reaction of the
      leukocyte subsets to coronary bypass surgery which is more related to the
      surgical trauma in general than to CPB in particular.

PMID- 9928853
TI  - Emergency coronary artery surgery after failed PTCA: myocardial protection with
      continuous coronary perfusion of beta-blocker-enriched blood.
AB  - BACKGROUND: Myocardial protection during cardiac surgery in patients with acute
      ischemia after failed PTCA remains a challenge. Our recent experimental work
      demonstrated that continuous coronary perfusion with warm beta-blocker-(Esmolol)
      enriched blood may be a useful alternative to current cardioplegia techniques,
      especially for compromised hearts. This technique was applied in our last 12
      patients after failed PTCA (beta-B). The purpose of this retrospective study was
      to compare this alternative myocardial protection technique with our standard
      technique of cold crystalloid cardioplegia (CP). METHODS: Between January 1994
      and January 1998 fifty-five patients (beta-B: n = 12; CP: n = 43) underwent
      emergency coronary artery bypass grafting within 24 hours after failed PTCA. The
      mean age in beta-B patients was 62+/-9 (SD) years, and 33% were female (CP: 59+/
      9 years, 42% female, p = NS). In beta-B patients 67% had myocardial infarction
      (MI) prior to coronary angioplasty, 67% had an ejection fraction (EF) >55%, and
      coronary vessel involvement (VI) was 2.1+/-0.7. CP patients had the following
      findings: MI rate 42%, EF >55% in 84%, VI was 2.2+/-0.6; p = NS. Operation
      commenced within 25-980 min after failed PTCA. Beta-B patients received 2.7+/-0.8
      grafts during 45+/-20 min continuous coronary perfusion with Esmolol enriched
      blood, whereas CP patients had 3.0+/-1.1 grafts in 42+/-17 min cross-clamp time,
      p = NS. RESULTS: The total hospital stay was significantly (p = 0.004) shorter
      for beta-B patients (18+/-8 days) compared to CP patients (27+/-12 days). 30-days
      mortality rate was 9% in CP patients, whereas none of the beta-B patients died.
      Postoperative low cardiac output occurred in only one patient (8%) of the beta-B
      group and was treated with an intra-aortic balloon pump (IABP). Eight (19%) of
      the CP patients required an IABP and in five (12%) patients an additional
      ventricular assist device was necessary (LVAD: n = 4; RVAD: n = 1). The need for
      circulatory support with inotropes was significantly lower in beta-B patients.
      Cumulative postoperative dosage of dopamine and dobutamine was 34516+/-40400
      microg/kg and 16221+/-26678 microg/kg respectively in CP patients. Beta-B
      patients required only 12457+/-14738 microg/kg (p = 0.02) dopamine and 5112+/
      7381 microg/kg (p = 0.01) dobutamine. Perioperative myocardial infarction
      occurred in 53% of the CP patients and 17% of beta-B patients (p = 0.046). Total
      CKmax was significantly (p = 0.003) higher in CP patients (812+/-531 U/L) than in
      beta-B patients (457+/-265 U/L). Four CP patients (9%) had acute postoperative
      renal failure requiring hemofiltration, and 11 CP patients (26%) had acute
      postoperative pneumonia. In beta-B patients one patient (8%) suffered from
      postoperative pneumonia (p = NS) and no patient had renal failure (p = NS).
      CONCLUSION: These clinical results appear to confirm our experimental data and
      suggest that continuous coronary perfusion with warm esmolol-enriched blood is
      superior to crystalloid cardioplegia in terms of in-hospital complications and
      mortality, especially for compromised hearts after failed PTCA.

PMID- 9928855
TI  - Pathophysiology of early failure of autologous aortic heart valves (ATCV).
AB  - BACKGROUND: Degeneration remains the major drawback of bioprostheses. Among
      various concepts to mitigate degeneration, the use of autologous pericardium for
      intraoperative construction of aortic valves (ATCV) was revived recently. Based
      on in-vivo studies the problem of tissue failure was claimed to be oversome by
      short immersion in glutaraldehyde. METHODS: Two often ATCV implanted 1994-1996
      had to be replaced because of valvular insufficiency due to leaflet shrinkage or
      tearing. Pathophysiology of failure was evaluated by light microscopy and immune
      histology, scanning electron microscopy (SEM) and determination of tissue calcium
      content (AAS). RESULTS: AAS revealed high calcium levels in the shrunken and low
      levels in the torn leaflets. Histology demonstrated extensive fiber degeneration
      without inflammation in the destructed and moderate degeneration in the intact
      leaflets. SEM showed smooth surfaces in the 'normal' and exposure of collagen in
      the degenerated leaflet associated with calcification. Tears occurred close to
      the stents. CONCLUSIONS: Failure of ATCV is characterised by either shrinkage and
      calcification despite a short tanning or by tearing related to the stent design.
      Clinical use of ATCV cannot be recommended at present.

PMID- 9928854
TI  - The role of coronary perfusion changes in cardiac dysfunction associated with
      brain death.
AB  - BACKGROUND: Previous studies described a hemodynamic instability in the potential
      organ donor which has clinical relevance for cardiac transplantation. The
      possible pathophysiological link between altered loading conditions, coronary
      perfusion, and cardiac function after brain death has not been investigated yet.
      Therefore this study was undertaken to investigate the role of coronary perfusion
      changes during brain death in cardiac dysfunction. METHODS: Dogs on
      cardiopulmonary bypass provided iso-volumetric left-ventricular (LV)
      contractions. By protocol, coronary perfusion pressure was kept at the level of
      mean aortic pressure. LV pressure, LV dP/dt, the slope of end-systolic pressure
      volume relationship (Emax), coronary blood flow (CBF), and myocardial oxygen
      consumption (MVO2) were measured. Brain death was induced by a subdurally placed
      balloon-catheter. RESULTS: Induction of brain death led to a transient
      hyperdynamic response with a significant increase of aortic and LV pressure,
      dP/dt, Emax, CBF, and MVO2. Thereafter, aortic pressure and, parallelly, LV
      pressure, dP/dt, Emax, CBF, and MVO2 decreased significantly. However, if
      coronary perfusion pressure was decoupled from aortic pressure and elevated to
      pre-brain death level, CBF and myocardial contractility were restored to baseline
      level. CONCLUSION: The impairment of coronary blood flow may contribute to
      decreased contractility after brain death.

PMID- 9928856
TI  - Diagnostic value of procalcitonin: the influence of cardiopulmonary bypass,
      aprotinin, SIRS, and sepsis.
AB  - BACKGROUND: The reasons for a systemic inflammatory response syndrome (SIRS)
      following ECC are not yet fully understood. Procalcitonin (PCT) blood levels may
      distinguish between bacterial infections and a non-bacterial systemic
      inflammation. We investigated the influence of ECC, ECC modified by application
      of aprotinin, systemic inflammation, and bacterial infection on the PCT values.
      METHODS: 20 CABG patients were randomized and divided in two groups. Group A
      served as the control group, while group B perioperatively received a high dose
      of aprotinin. Blood samples for measurement of PCT were taken 6 times
      perioperatively. Furthermore, blood samples were taken from 20 preoperatively
      comparable patients who suffered from bacterial infection (n = 10) (group C) or a
      SIRS (n = 10) (group D) after ECC; in these groups PCT was determined daily after
      the onset of inflammation. RESULTS: There was no significant elevation of PCT in
      group A or B at any time. In sepsis patients a significant elevation of PCT was
      seen, with the peak level of 18.6+/-6.3 ng/ml on the second day after diagnosis;
      the PCT level of SIRS patients remained constantly low (<0.9 ng/ml). CONCLUSIONS:
      In this study it was demonstrated that ECC and the use of aprotinin did not have
      any influence on the secretion of PCT. A systemic bacterial infection caused a
      significant increase of PCT, whereas PCT values remained normal in case of a
      SIRS. So it seems to be possible to distinguish between a primary SIRS and a
      bacterial sepsis by means of PCT.

PMID- 9928857
TI  - Percutaneous dilatational tracheostomy: results and long-term outcome of
      critically ill patients following cardiac surgery.
AB  - BACKGROUND: Tracheostomy is widely regarded as the method of choice for long-term
      airway control in critically ill patients. The advantages of tracheostomy have to
      be balanced against the surgical risks of conventional surgical tracheostomy.
      However, the alternative technique of percutaneous dilatational tracheostomy
      (PDT) has been associated with fewer procedure-related complications. METHODS:
      The results of PDT following cardiac surgery were investigated in a prospective
      study (1/1995-9/1997). The procedure of Ciaglia (1985), a modified Seldinger
      technique, was performed under endoscopic guidance in 88 patients, 30 women and
      58 men, with a mean age of 56.6+/-14.5 years. RESULTS: PDT was successfully
      performed in all cases after a mean of 14.6+/-9.0 days of translaryngeal
      intubation. No serious procedural complications occurred; a minor hemorrhage
      occurred in 12 patients and a cuff defect in 2 patients. 49 patients (55.7%) were
      weaned from mechanical ventilation, and 45 patients (51.1%) were decannulated
      after a mean tracheostomy duration of 18.9+/-27.2 days. 38 patients died of their
      underlying disease while still being mechanically ventilated. A total of 20
      postprocedural complications were observed in 15 patients: stomal infection (7),
      minor hemorrhage (4), tracheal stenosis (3), tube displacement (2), delayed wound
      healing (2), soft-tissue hemorrhage (1), and organ hemorrhage (1). During long
      term follow-up a good functional and cosmetic result could be documented in the
      majority of 35 patients. CONCLUSIONS: PDT can be performed safely in patients
      following cardiac surgery as a bedside technique with a low incidence of
      procedural and postprocedural complications and an acceptable functional and
      cosmetic long-term outcome. Further studies are needed to define the optimal
      timing of PDT after translaryngeal intubation.

PMID- 9928858
TI  - Childhood chronic pleural empyema: a continuing surgical challenge in developing
      countries.
AB  - BACKGROUND: Surgical treatment may be necessary in childhood chronic pleural
      empyema. METHODS: Over a 21-year period 642 children with pleural empyema were
      hospitalized and 104 of them underwent surgical treatment. The records of the
      children who underwent surgery for the treatment of empyema were retrospectively
      reviewed to describe the role, indications, and results of surgical treatment of
      childhood chronic pleural empyema. RESULTS: Etiologic diseases or conditions
      leading to empyema were pneumonia in 69 patients, tuberculosis in 13, hydatid
      cyst in eight, postpneumonectomy empyema in five, and other causes in nine
      patients. Indications for surgery were severe pleural thickening in 54 cases
      (51.9%), trapped lung in 36 cases (34.6%), loculated empyema in eight cases
      (7.7%) and broncho-pleural fistula in six cases (5.8%). Operations performed were
      decortication in 90 patients, pulmonary resection and decortication in seven,
      muscle flap closure in five, and pneumonectomy in two. Success rates in the
      treatment of nonspecific and tuberculous empyema were 93% and 54%, respectively.
      CONCLUSIONS: Surgical treatment is still necessary in childhood pleural empyema
      in developing countries, and success rates are very high in nonspecific pleural
      empyema and acceptable in tuberculous pleural empyema.

PMID- 9928859
TI  - Comparison of virtual and fiberoptic bronchoscopy.
AB  - Preoperative diagnostic procedures in the treatment of non-small-cell lung
      carcinoma (NSCLC) include fiberbronchoscopy (FBS) and CT scanning of the thorax
      and abdomen. The introduction of double-detector helical computed tomography has
      led to improved image resolution which allows three-dimensional reconstruction of
      the bronchial tree. A special computer simulation provides a virtual endoscopic
      view into the inner surface of the bronchial system. In order to determine
      whether the so-called virtual bronchoscopy (VBS) accurately reflects the anatomic
      situation of the bronchial tree, neoplastic lesion, and postoperative control of
      sleeve resections, we performed a virtual bronchoscopy in 24 patients with NSCLC
      and in 6 patients following sleeve resections and compared the results with the
      findings of fiberoptic bronchoscopy. An anatomic computer simulation of the
      bronchial tree was created in 100% of the investigated patients. Central tumor
      stenosis or occlusion was visualized by VBS as well as by FBS. In peripheral
      tumorous lesions VBS revealed the correct diagnosis in only 75%. VBS, however,
      enables viewing beyond the stenosis. FBS remains the gold standard in the
      endoscopic diagnostic procedures, showing not only airway patency but also
      mucosal changes in the vicinity of the tumorous lesion. VBS, however, gives
      further information about the poststenotic area in occlusive main bronchus
      stenosis. Furthermore, adequate control investigation of airway patency in
      patients following sleeve resections or stent implantation can be performed by
      VBS.

PMID- 9928860
TI  - Results after surgery in stage-I bronchogenic carcinoma.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate prognostic
      factors for recurrence-free survival in stage-I non-small-cell bronchogenic
      carcinoma. METHODS: During 9 years, 338 consecutive patients were operated on for
      stage-I bronchogenic carcinoma. Patients with small-cell carcinoma (n = 14),
      prior malignancies in locations other than pulmonary (n = 41), and patients with
      incomplete data on prognostic factors (n = 11) were excluded. Of the remaining
      272 patients 226 were men. Mean age was 63 years (40 to 81 years). The resections
      performed comprised 215 lobectomies and bilobectomies, 36 segmentectomies and
      wedge resections, and 21 pneumonectomies. According to the number of sites of
      dissected lymph nodes 3 subgroups were formed: group A with 0 to 4 (n = 71), B
      with 5 to 6 (n = 118), and C with 7 to 10 sites (n = 83). Median follow-up was 46
      months. RESULTS: Three patients (1.1 %) died within 30 days of operation. In 3
      patients the resection was revealed to be not radical (R1). At the end of follow
      up, 191 patients were alive, 174 of these without recurrence. Eighty-one patients
      had died, 53 associated with tumor recurrence. Four patients had died of non
      pulmonary malignancies. Twenty-two patients died of causes not related to tumor
      disease. In 2 patients the cause of death could not be determined
      retrospectively. Overall 5-year survival was 65% (95% confidence interval [CI] 58
      72%), recurrence-free survival 59% (CI 51-66%). Significant prognostic factors
      for recurrence-free survival were T stage (relative risk [RR] 1.7 for T2 vs. T1,
      CI 1.0-3.0), age (RR 1.9 for >70 years vs. < or =70 years, CI 1.1-3.1), adeno
      cell type (RR 2.3 vs. squamous cell, CI 1.4-4.0), as well as lymphangiosis
      carcinomatosa (RR 2.3, CI 1.2-4.4). Extent of operative resection, extent of
      lymphadenectomy, and sex did not influence survival. CONCLUSION: 5-year survival
      of our patients was in the range reported in literature. Most patients died of
      distant metastases. Our retrospective study probably underestimated the
      occurrence of second primary cancers of the lung. Limited resection in poor-risk
      patients showed equivalent results to lobectomy. The extent of lymph-node
      resections had no influence on survival of stage-I patients, however, it must be
      remembered that positive results in lymph nodes shift patients to higher stages.

PMID- 9928861
TI  - Transthoracic pacemaker lead insertion via the right atrium.
AB  - This case reports a right mediastinotomy approach to place DDD pacemaker leads in
      a patient without venous access in whom an epicardial lead was malfunctioning.

PMID- 9928862
TI  - Extracardiac repair versus intracardiac baffle repair of complex unroofed
      coronary sinus.
AB  - Complex unroofed coronary sinus with a persistent left superior vena cava has as
      its commonest major associated intracardiac anomaly a partial or complete
      atrioventricular canal defect. In this clinical setting, biventricular repair
      with construction of a complex intra-atrial baffle from the pulmonary veins to
      the mitral valve has a reported mortality rate of as high as 50%. Looking for an
      improvement, we have carried out an extracardiac repair of the anomalous systemic
      venous component with atrial septation. In 2 infants (aged 7 and 12 weeks) with
      unroofed coronary sinus, bilateral superior venae cavae, right isomerism, and
      complete atrioventricular canal, in addition to patch closure of the ventricular
      component of the atrioventricular septal defect, a baffle was constructed between
      the pulmonary veins and the mitral valve. In four subsequent infants (aged
      7,10,16, and 20 weeks) with unroofed coronary sinus, bilateral superior venae
      cavae, complete atrioventricular canal, right isomerism (n = 2), and mild
      infundibular stenosis (n = 1), repair consisted of end-to-side anastomosis of the
      left superior vena cava to the right superior vena cava and complete repair of
      the atrioventricular canal and associated conditions. There was no mortality. The
      early postoperative course in the two patients with intra-atrial baffle was
      characterized by increased left-atrial pressure (18 and 20 mm Hg), with varying
      degrees of pulmonary venous congestion, supraventricular tachycardias, and
      systemic hypotension. The pulmonary venous congestion increased, so that one
      patient was successfully converted 10 weeks postoperatively to an extracardiac
      repair with septation of the atria and the other will probably follow. In the 4
      patients with a primary extracardiac repair, the hemodynamic result was
      excellent, with a median left-atrial pressure of 11 mm Hg on the first
      postoperative day. At a median follow-up of 12 months, all 5 patients with an
      extracardiac repair are clinically well with widely patent anastomoses between
      the left and right superior venae cavae. The extracardiac repair technique for
      complex unroofed coronary sinus, as opposed to the intra-atrial baffle repair,
      avoids creation of a small and low-compliance left-atrial compartment with the
      potential for development of pulmonary venous congestion.

PMID- 9928863
TI  - Mediastinal perforation and contralateral hemothorax by a chest tube.
AB  - Tube thoracostomy is an invasive and common procedure that is often life-saving,
      but by no means innocuous. We describe herein a case of chest trauma in which the
      chest tube crossed through the mediastinum between aorta and esophagus and
      penetrated the contralateral pleural cavity causing mild hemothorax. A literature
      search has failed to identify a similar case: the misplacement was detected in a
      control radiograph which led to early adjustment of the tube and no sequalae.

PMID- 9928864
TI  - Mediastinal paraganglioma: a case report.
AB  - Mediastinal paragangliomas are unusual neoplasms that have been described in the
      medical literature. The microscopic features of paragangliomas are well
      established and are essentially similar, regardless of the anatomic site,
      although some minor differences have been noted according to the location of the
      tumor. We present a case of nonfunctioning anterior mediastinal paraganglioma in
      a 33-year-old woman. The mediastinal tumor was accidentally discovered on a
      thoracic tomographic scan performed for an unrelated minor nasal discomfort.
      Diagnosis was confirmed by 123I-metaiodobenzylguanidine scintigraphy and
      mediastinoscopy. Complete resection of the tumor was done through a median
      sternotomy and the patient received intraoperative radiotherapy.

PMID- 9928865
TI  - 'Soft' Snaring of the coronary artery in minimally-invasive coronary surgery.
AB  - A technique is described that allows a simple and safe temporary occlusion of the
      coronary artery in beating heart procedures using monofilament stay sutures
      underlaid with small pericardial pads. Postoperative serial levels of Troponin I
      remained low (<4 ng/L) and control angiography revealed no stenosis in the distal
      coronary artery.

PMID- 9928866
TI  - Intraoperative visualization of coronary artery fistula using medical dye.

PMID- 9928867
TI  - Garlic, onion and cereal fibre as protective factors for breast cancer: a French
      case-control study.
AB  - The role of diet on breast cancer risk was investigated in a case-control study
      of 345 patients diagnosed with primary breast carcinoma between 1986 and 1989 in
      the north-east of France (Lorraine). For each case, one control was matched for
      age (+/-3 years) and socio-economic status. The dietary history questionnaire
      consisted of a self-administered food frequency questionnaire, a 6-day food diary
      and an energy expenditure record. It also elicited personal characteristics and
      medical history. While taking into account total caloric intake and established
      risk factors, breast cancer risk was shown to decrease as consumption of fibre (p
      value for trend = 0.03), and garlic and onions (p value for trend <10(-6))
      increased. This study also supports the epidemiologic evidence that saturated fat
      intake and breast cancer risk are associated in post-menopausal women (p value
      for trend = 0.03). Conversely, it suggests that unsaturated fat intake could
      lower the risk in the same subgroup (p value for trend = 0.03). Our findings on
      protective factors of breast cancer could induce effective preventive measures
      and warrant further experimental investigations to isolate specific subfractions.

PMID- 9928868
TI  - Cancer increased after a reduction of infections in the first half of this
      century in Italy: etiologic and preventive implications.
AB  - Two rate ratios indicating the disappearance of infections and the growth of
      tumours, respectively, were simultaneously plotted against the calendar years of
      occurrence in a period during which mortality rates were reasonably comparable to
      incidences. The transformation used gave upward trend time variations for
      infectious diseases, providing strong evidence that in Italy during the first
      half of this century variations in infectious diseases preceded variations in
      cancer. While some bacteria and viruses are known to be cancer agents, sparse
      studies indicate that a host's immune response to infection may destroy cancer
      cells. With a decreasing mortality from infectious illnesses, there may have been
      a reduction in the activation of immunological mechanisms against transformed
      cells in early phases of carcinogenesis. If cancer growth is a consequence of a
      lower exposure to chronic sublethal doses of microbial agents, bacterial
      derivates could be potentially useful in cancer chemoprevention.

PMID- 9928869
TI  - Cardiovascular risk factors and educational attainment in Southern Spain: a study
      of a random sample of 3091 adults.
AB  - STUDY OBJECTIVE: To analyze the associations between educational attainment and
      major cardiovascular disease risk factors in the Murcia Region (Southern Spain).
      DESIGN: During 1992 we conducted a survey by interview, with multi-stage random
      sampling, representative of the general adult population. We calculated odds
      ratios (OR) and trends by logistic regression as a measure of the association
      between educational levels and cardiovascular risk factors, taking the university
      level as the reference category. PARTICIPANTS: A total of 1514 men and 1577 women
      aged between 18 and 65 years was included in the study. Rate of response to the
      questionnaire was 61%. Seventy-eight percent of the respondents provided a blood
      sample. A telephone survey on a representative sample of non-respondents (n =
      347), showed no statistical differences in the level of studies. MEASUREMENTS: We
      asked for educational level (highest schooling qualification completed), and
      according to the WHO MONICA protocol we measured: blood pressure, cigarette
      smoking, height, weight and total cholesterol, triglycerides and HDL-cholesterol.
      We also obtained the leisure-time physical activity by a validated questionnaire.
      MAIN RESULTS: In a context of a low level of schooling, mainly among the older
      age groups, the prevalence of risk factors except smoking in women is higher in
      the lower educational levels. Systolic blood pressure tends slightly to increase
      as schooling level decreases (both genders, p<0.02). Conversely, serum total
      cholesterol and triglycerides decrease with higher level of schooling in men. The
      high levels of HDL-cholesterol observed in all educational groups show no trend
      in both genders. Arterial hypertension in men and women and overweight in women
      tend to decrease with higher educational attainment. Moreover, higher level of
      education is associated with vigorous physical exercise in both genders and
      cigarette smoking in women. We observed the strongest significant magnitude
      association in nonschooling with hypertension in men (OR: 1.82; 95% CI: 1.15,
      2.89), in women (OR: 2.39; 95% CI: 1.05, 5.44), and with overweight in women (OR:
      3.22; 95% CI: 1.97, 5.27), meaning that compared to people at the university
      level, people without schooling showed two to three times higher prevalence of
      hypertension and overweight (only women). Also non-schooling obtained the lowest
      significant association with protective physical exercise for coronary heart
      disease in men (OR: 0.32; 95% CI: 0.18, 0.56) and in women (OR: 0.31; 95% CI:
      0.15, 0.62) pointing out that people at the university level of education had
      three times the prevalence of vigorous physical activity than their non
      schoolarized counterparts. CONCLUSIONS: After adjusting for environmental
      factors, in our adult general population, educational attainment is inversely
      associated with arterial hypertension in both genders and with overweight in
      women, and directly associated with cigarette smoking in women and with leisure
      time physical activity in both genders.

PMID- 9928870
TI  - Six years of sentinel surveillance of hepatitis B in general practice in France.
AB  - Despite the availability of a safe and efficacious vaccine, new cases of
      infection by hepatitis B virus (HBV) still occur at a substantial rate. This
      increases the current prevalence of chronic HBV carriers (10% of newly infected
      subjects) and in the long run, will raise the incidence of chronic liver disease.
      The surveillance of viral hepatitis commenced in December 1990 by the French
      sentinel network for electronic surveillance of communicable diseases. Between
      1991 and 1996, a decrease in the annual incidence was observed although it was
      not significant (p = 0.06). The mean number of cases for this period was 12 per
      100,000 inhabitants. The sex ratio (M/F) was 1.6 (p<0.01) and the median age, 32
      years. Heterosexual transmission was suspected in 25% of cases, homo-bisexual
      transmission in 10%, use of injected drugs in 19%, percutaneous exposure in 9%,
      and blood transfusion or hemodialysis in 6%. Although the incidence of HBV
      infection is decreasing, the prevalence of chronic infection will continue to
      rise. However, the universal hepatitis B immunisation strategy proposed by WHO
      will dramatically limit the expansion of the population of chronically infected
      subjects if high coverage is achieved rapidly.

PMID- 9928871
TI  - Certifying the elimination of poliomyelitis from Europe: advancing towards global
      eradication.
AB  - Indigenous wild polioviruses have been virtually eliminated from the 51 countries
      of the European Region of the World Health Organization (WHO), an achievement
      that is of critical importance to the global initiative to eradicate
      poliomyelitis by the year 2000. An international commission has been established
      to certify the elimination of poliomyelitis from this region. European countries
      have recently been requested to establish National Certification Committees to
      review and submit the necessary documentation and surveillance data. In some
      Western European countries where polio has not been reported for many years, the
      challenge will be to produce robust evidence demonstrating both the current
      absence of wild poliovirus and the means to promptly detect and respond to
      possible importations of wild poliovirus for the next several years, up to global
      eradication and the cessation of polio vaccination. KEY MESSAGES: 1. laboratory
      based surveillance with collection of faecal specimens is necessary to
      demonstrate the absence of indigenous wild poliovirus 2. certification can only
      occur after all countries have demonstrated the absence of indigenous wild
      polioviruses for at least 3 years and have the means to detect and respond to
      importations of wild poliovirus for several years into the future 3. any single
      case of poliomyelitis in Europe now requires an immediate public health response
      which includes virological investigation and prompt notification to the World
      Health Organization.

PMID- 9928872
TI  - Risk factors for high blood lead levels among the general population in Taiwan.
AB  - PURPOSE: Environmental and occupational lead pollution is a common problem in
      both developing and industrialized countries. The purpose of this study is to
      evaluate the risk factors for high blood lead levels among the general population
      in Taiwan. METHODS: After multi-stage sampling, we randomly selected 2803
      subjects (1471 males and 1332 females) for this study. Univariate and
      multivariate logistic regression analyses were conducted to evaluate the risk of
      high blood lead. To control for differences in age and gender, all analyses were
      with age-adjusted and gender-stratified. RESULTS: Among males, the mean age is 46
      years (15 to 85 years), mean and median blood lead levels is 7.3 and 6.3
      microg/dl, respectively. Among females, the mean age is 43 years (15 to 84
      years), mean and median blood lead level is 5.7 and 4.8 microg/dl, respectively.
      Among males, the history of herbal drug use, drinking water from well or spring
      sources, and occupational lead exposure are significantly different between
      relatively high and normal blood lead level subjects. The history of occupational
      lead exposure, history of herbal drug use, and well or spring sources of drinking
      water are the major risk factors for high blood lead with odds ratio of 4.62 (95%
      CI: 2.82-7.55), 3.09 (95% CI: 1.60-5.97), 2.06 (95% CI: 1.13-3.76), and 2.37 (95%
      CI: 1.39-4.04), respectively. Among females, these characteristics remain
      important except the sources of drinking water. The history of herbal drug use
      and occupational lead exposure become the major risk factors for high blood lead
      with odds ratio of 2.94 (95% CI: 1.26-6.88) and 7.72 (95% CI: 3.51-16.99),
      respectively. In multivariate logistic regression analyses, we find that the risk
      factors for high blood lead in both genders include a history of herbal drug use
      and occupational lead exposure. Among males, the drinking water sources and
      factories in the neighboring areas are also significant factors for high blood
      lead. CONCLUSIONS: For the goal of reducing prevalence of high blood lead by the
      year 2000, the improvement and monitoring of the working environment, the careful
      attention to herbal drug use and the lead-free drinking water sources should be
      executed as thoroughly as possible to reduce the probability of lead pollution.

PMID- 9928873
TI  - Functional ability among elderly people in three service settings: the
      discriminatory power of a new functional ability scale.
AB  - The purpose is to assess the discriminatory power of the Avlund scales: (1) by
      assessing the ability of the scales to discriminate between three different
      populations of elderly people, and (2) by studying groups with a poor fit between
      use of formal home care and functional ability. The study included (A) all
      residents in new sheltered housing facilities (response rate 68%, n = 102), (B) a
      random sample of users of home care (response rate 67%, n = 435), and (C) a
      random sample of individuals not using home care (response rate 74%, n = 501).
      All participants were 60+ years old. Data were collected by personal interviews
      (group A) and by postal questionnaires (group B and C). Functional ability was
      measured by The Avlund Mob-T scale about tiredness related to mobility and the
      Mob-H scale about need of help to mobility. Both scales were able to distinguish
      the three sub-populations. The whole range of the Mob-T scale was used in all
      three subpopulations, and the whole range of the Mob-H scale was used among the
      oldest residents and the oldest users of home care. A small group of well
      functioning users of home care (n = 52) was characterized by good self-rated
      health, good hearing, vision and memory abilities; they gave more help to others,
      had higher social participation, and lived alone (only the women). A somewhat
      lager group of poor functioning non-users of home care (n = 266) had the opposite
      characteristics. In addition, they were older, had a poor social network and poor
      social support.

PMID- 9928874
TI  - Congenital cytomegalovirus infection in a northern Italian region. NEOCMV Group.
AB  - Knowledge of the prevalence of congenital cytomegalovirus infection is necessary
      to evaluate the need for prevention. We performed a multicentre one-year study
      involving 11 neonatology divisions to ascertain the prevalence in Lombardy.
      Cytomegalovirus was isolated by culturing saliva samples from all babies born (n
      = 1268) of two 15-day sample periods and from 185 neonates with suspected
      congenital CMV based on clinical and laboratory findings and the history. The
      overall prevalence of congenital infection was 0.47% (6/1268) in the sample
      period group and 5% (9/185) in the second group. Clinical monitoring revealed
      sequelae in two of three children with symptomatic infection and no asymptomatic
      child at age two years. In a subgroup of 205 babies including 14 of the infected
      infants we also evaluated a test to detect cytomegalovirus DNA in the Guthrie
      cards obtained in neonatal screening for genetic and metabolic disorders. The
      test's sensitivity was 100% and specificity 98.5%, encouraging its use for early
      identification of infected neonates and for large epidemiological studies.

PMID- 9928876
TI  - Prevalence of IgM and IgG antibodies to Toxoplasma gondii in blood donors in the
      Czech Republic.
AB  - Blood donors (n = 663) from the Novy Jicin district, Czech Republic, were
      examined for the presence of antibodies to Toxoplasma gondii. The indirect
      fluorescent antibody test was used to simultaneously detect IgM and IgG
      antibodies. Titres > or =20 were considered positive. The seroprevalence of IgM
      and IgG antibodies was 2.4% and 32.1%, respectively. Periods, for how long the
      blood donors were infected, are discussed.

PMID- 9928875
TI  - First isolation of Francisella tularensis subsp. tularensis in Europe.
AB  - Francisella tularensis subsp. tularensis is the common causal agent of tularemia
      in the USA and Canada, while F. tularensis subsp. palaearctica (holarctica)
      occurs in Europe, Asia, and to a minor extent in North America. F. tularensis
      subsp. mediaasiatica was found only in central Asia in a part of the former
      Soviet Union. Of the total of 155 F. tularensis strains isolated over the years
      1978-1996 during the surveillance of tularemia in Slovakia, 65 were from small
      mammals, 68 from ticks and 22 from mites and fleas. They were characterized and
      classified by basic markers of infraspecific taxonomy in tests in vitro and
      compared with type strains of three subspecies and biovars of F. tularensis.
      Comparative studies have revealed biological properties characteristic of F.
      tularensis subsp. tularensis in 17 strains isolated from fleas and mites
      parasiting on small terrestrial mammals, collected in the Danube region, near
      Bratislava. These strains fermented glycerol, glucose, were positive for
      citrulline ureidase and sensitive to erythromycin, in contrast to the other 138
      isolates classified as F. tularensis subsp. palaearctica (holarctica), biovar II,
      which fermented only glucose, were negative for citrulline ureidase and resistant
      to erythromycin. Two selected pairs of isolates with properties characteristic of
      F. tularensis subsp. palaearctica (holarctica), biovar II (SE-210, SE-234) and of
      F. tularensis subsp. tularensis (SE-219, SE-221), as shown in tests in vitro,
      were further examined for their pathogenicity on white mice, guinea pigs and
      domestic rabbits. In tests of virulence on domestic rabbits, the isolates SE-210
      and SE-234 had low pathogenicity, while the isolates SE-219 and SE-221 exhibited
      high pathogenicity, which along with their biochemical properties confirmed their
      identification as strains of F. tularensis subsp. tularensis. The first findings
      of the highly virulent strains of F. tularensis subsp. tularensis in Europe
      indicate a serious event from epidemiologic and epiozootologic aspects, requiring
      systematic surveillance.

PMID- 9928877
TI  - Molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA)
      in a university hospital in Italy.
AB  - The molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA)
      in a university hospital in Italy was studied in a five-month period in 1996,
      during which all S. aureus isolated were collected. All MRSA isolates (95) and a
      sample of methicillin-susceptible S. aureus (20) were typed with a variety of
      phenotypic and genotypic methods. Clonal identities were determined by pulsed
      field gel electrophoresis (PFGE) of chromosomal SmaI digests and, for MRSA
      isolates, by probing ClaI digests with a mecA probe and a Tn554 probe. Overall,
      MRSA represented 32.3% of all isolates, with very high percentages from the
      intensive care units (adult and neonatal). PFGE after restriction with SmaI
      resolved genomic DNA of 95 MRSA strains into 26 major PFGE patterns. The use of
      southern blot hybridization of ClaI genomic digests with mecA and Tn554 allowed
      us a significant increase in discrimination, differentiating at least 32
      different clones. Two major clones, however, each sharing common ClaI-mecA and
      Tn554 type and PFGE pattern as well as a common resistance phenotype, represented
      more than 50% of all MRSA isolates. The recovery of these two clones in the
      majority of the isolates of adult and neonatal intensive care units,
      respectively, is indicative of typical nosocomial outbreaks and clonal spread. It
      is concluded that intensive care units are major areas requiring preventative
      interventions.

PMID- 9928878
TI  - Prevalence of antibodies to Rickettsia conorii Ricketsia africae, Rickettsia
      typhi and Coxiella burnetii in Mauritania.

PMID- 9928879
TI  - Chromogranin A inhibits dopamine release from rat striatal slices.
AB  - Chromogranin A (CGA), a prohormone and a protein component of endocrine and
      neural secretory granules, neuritic plaques in Alzheimer's disease and Lewy
      bodies in Parkinson's disease, inhibited the release of dopamine (DA) from
      perfused rat striatal slices. Dopamine release was stimulated by a pulse of high
      potassium (40mM) medium introduced at 20 minutes (K1) and 55 minutes (K2)
      following equilibration. The ratio of K2/K1 was 0.80+/-0.04 in control tissues,
      but fell significantly to 0.26+/-0.08 when 100nM purified CGA was added prior to
      the second potassium pulse. This reduction in DA release was equivalent to that
      seen when calcium was excluded from the buffer (0.19+/-0.05). Pancreastatin, a
      centrally active peptide product of CGA, had no effect on stimulated DA release
      (0.77+/-0.06), although it, as well as the other treatments, did reduce basal DA
      release. It is likely that the parent molecule itself, CGA, or an as yet
      unidentified product is responsible for inhibition of K-stimulated striatal DA
      release.

PMID- 9928880
TI  - Alteration in L-DOPA evoked dopamine and DOPAC output under conditions of
      impaired vesicular dopamine storage.
AB  - We examined the effect of L-dihydroxyphenylalanine (L-DOPA) infusion in vitro
      upon dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) output from superfused
      corpus striatum of vehicle and reserpine or tetrabenazine (TBZ) treated male
      rats. Specifically, we tested the effects of two 20-min infusions of L-DOPA (5
      uM) upon DA and DOPAC output (pg/mg/min) in reserpine (5 mg/kg, i.p., 24 hours
      before sacrifice; n=11), TBZ (30 mg/kg, i.p. 1 hour before sacrifice; n=8) or
      vehicle (n=21) treated rats. There was an overall significantly higher L-DOPA
      evoked DA output from the vehicle (12.22+/-1.74) versus reserpine (4.39+/-2.40)
      (p < 0.05), but not TBZ (9.16+/-2.81) treated rats. In addition, the DA response
      to the second L-DOPA infusion was significantly increased over that of the first
      response in the vehicle (9.40+/-2.11 vs. 15.04+/-2.78) (p < 0.05), but not
      reserpine or TBZ treated rats. The overall DOPAC outputs did not achieve a
      statistically significant difference among all treatment groups. However, the
      DOPAC outputs following the second L-DOPA infusion were significantly reduced in
      reserpine (41.15+/-6.10 vs. 20.27+/-4.54) and TBZ (21.38+/-4.41 vs. 10.87+/-2.36)
      (both p < 0.05), but not vehicle (28.99+/-4.00 vs. 24.91+/-4.78) treated rats. We
      conclude that: 1) the storage capacity of DA neurons is one of the important
      elements involved in affecting L-DOPA's effects upon DA and DOPAC output, 2) the
      shunting of storage to metabolism may represent a common characteristic in
      impaired nigrostriatal dopaminergic system, and 3) TBZ may operate differently
      from reserpine in the nigrostriatal dopaminergic system.

PMID- 9928881
TI  - The role of catecholamines in desmopressin induced locomotor stimulation.
AB  - Central and peripheral administration of DDAVP increase locomotor activity in
      rats in doses that alter brain dopamine neurochemistry. In order to delineate the
      role of catecholamines in this behavioural effect of DDAVP, the effects of
      different catecholamine manipulating agents on DDAVP-induced locomotor
      stimulation were studied in rats. The catecholamine depleting agent reserpine (5
      mg/kg), administered alone or together with the catecholamine synthesis inhibitor
      alpha-methyltyrosine (250 mg/kg), completely prevented the locomotor stimulatory
      effect of DDAVP. The dopamine D1 receptor antagonist Sch-23390 (0.01 and 0.03
      mg/kg) significantly antagonized the DDAVP-induced locomotor stimulation when
      administered in the higher dose, that also produced a significant reduction of
      locomotor activity per se, whereas the dopamine D2 receptor antagonist raclopride
      (0.08 and 0.16 mg/kg) had no significant effect. The two dopamine blockers
      administered together produced a significant, dose-dependent reduction of DDAVP
      induced locomotor stimulation, while controls were not significantly affected.
      Also the alpha-adrenoceptor antagonist phenoxybenzamine decreased the DDAVP
      induced locomotor stimulation in a dose (20 mg/kg) that did not influence
      locomotor activity in controls, and, finally, administration of Sch-23390,
      raclopride and phenoxybenzamine antagonised the DDAVP-induced effect in a dose
      combination that failed to influence locomotor activity per se. In vivo
      microdialysis experiments in awake, freely moving rats indicated that DDAVP
      increases dopamine overflow in the nucleus accumbens, a brain area of importance
      for initiation of locomotor activity, by approximately 25%, as compared to
      baseline levels. Taken together, these results indicate that the central
      stimulatory action of DDAVP involves granula-mediated dopamine release and
      subsequent activation of dopamine D1 and D2 receptors, and that alpha
      adrenoceptors possibly also are involved.

PMID- 9928882
TI  - Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain
      slices as revealed by a new positron-based imaging technique.
AB  - The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic
      acetylcholinergic receptor (mAChR) binding was investigated in living brain
      slices by use of a novel positron-based imaging technique. Fresh rat brain slices
      were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a mAChR
      antagonist, in oxygenated Krebs-Ringer solution at 37 degrees C. During
      incubation, time-resolved imaging of [11C]NMPB binding in the slices was
      constructed on the storage phosphor screens. Addition of triazolam (1 microM)
      plus muscimol (30 microM), a GABA(A) receptor agonist, to the incubation mixture
      decreased the specific binding of [11C]NMPB. Ro15-1788, a BZ receptor antagonist,
      prevented this effect, indicating that the effect was exerted through the
      GABA(A)/BZ receptor complex. These results demonstrated that stimulation of the
      GABA(A)/BZ receptor lowers the affinity of the mAChR for its ligand, which may
      underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such
      effect in the P2-fraction instead implies that the integrity of the neuronal
      cells and/or their environment is prerequisite for the modulation of mAChR by
      GABA(A)/BZ stimulation.

PMID- 9928883
TI  - Influence of ethanol on the pentylenetetrazol-induced kindling in rats.
AB  - The effects of ethanol on the development of pentylenetetrazol (PTZ)-kindling as
      well as on fully PTZ-kindled convulsions in rats were investigated. Ethanol (0.5,
      1.0 and 1.5 g/kg i.p.) administered 15 min prior to each PTZ-injection (35 mg/kg
      i.p.; 3 times/week) significantly inhibited the progressive seizure development
      compared to saline-treated controls. For the higher doses of ethanol the kindling
      process was restricted to seizure stages of 1 or 2. Tolerance to this
      antiepileptogenic action did not occur even after 20 PTZ-stimulations. In a
      second series of experiments, 0.5 g/kg ethanol administered 10h before each PTZ
      injection facilitated the rate of kindling development after 7 to 10 PTZ
      injections, while the higher doses of ethanol did not modulate or even slightly
      reduced the seizure development. In a third test, intermittent administration of
      a high dose of ethanol (2 g/kg p.o.; twice daily for 6 days) before the kindling
      procedure (0.5 g/kg i.p. ethanol 10h prior to each PTZ-injection), significantly
      intensified the kindling development. In addition, studies with fully PTZ-kindled
      rats demonstrated that ethanol (0.1 to 1.5 g/kg i.p.), given 15 min prior or 2
      min after PTZ, reduced the seizure severity in a dose-dependent manner. In
      conclusion, the present findings provide evidence for pronounced
      antiepileptogenic and anticonvulsant effects of ethanol after acute application,
      whereas repeated administration of high doses with longer withdrawal periods
      leads to proconvulsant actions, possible mediated via neuroadaptive changes in
      NMDA and/or GABA(A) receptor-related mechanisms.

PMID- 9928886
TI  - Glucose minimally attenuates scopolamine-but not morphine-induced deficits on a
      water maze alternation task.
AB  - In a previous study, daily injections of glucose, 100 and 250 mg/kg i.p., in
      Sprague-Dawley rats failed to either facilitate acquisition or to ameliorate
      scopolamine- or morphine-induced deficits on a water maze alternation task
      (Means, et al., 1996). The present study demonstrates that daily injections of 1
      g/kg minimally ameliorates a scopolamine-induced deficit on the water maze
      alternation task in Sprague-Dawley rats. However, daily glucose injections of 1,
      2 and 4 g/kg failed to improve performance during acquisition or to diminish
      morphine-induced deficits on the task. The failure of daily administration of
      glucose to facilitate acquisition or reverse morphine-induced deficits was not
      due to the daily injection procedure nor to stress elevated glucose levels
      resulting from exposure to the task. It is suggested that the effects of glucose
      on memory are task dependent, with facilitation being more easily demonstrated on
      tasks for which animals have an innate bias to perform the correct response or
      the ability to acquire in very few trials.

PMID- 9928885
TI  - Effect of repeated immobilization on serotonin metabolism in different rat brain
      areas and on serum corticosterone.
AB  - The effect of daily repeated 10 min immobilization on the serotoninergic
      neurotransmission and serum corticosterone levels was studied. Male Lewis rats
      were immobilized for a 10 min period daily once or on 5 consecutive days.
      Serotoninergic neurotransmission was followed using differential in vivo pulse
      voltammetry with carbon fibre electrodes measuring extracellular 5
      hydroxyindoleacetic acid (5-HIAA) levels. Recordings were performed in brain
      areas involved in the control of behaviour, mood, and stress response such as the
      frontal cortex, the hippocampal CA-3 and dentate gyrus, the striatum, and the
      raphe nuclei dorsalis (NRD) and medialis (MRN). The first immobilization resulted
      in an increase of the extracellular 5-HIAA levels in all areas under study,
      except the striatum where no reaction was observed. The major effect was recorded
      in the frontal cortex, showing an increase of about 400% as compared to control,
      which lasted for 3h after the end of the immobilization period. Beginning on day
      2 in all areas, except the striatum, a consecutive habituation to the stressor
      seemed to occur, since the stress-induced increase in the voltammetric signal was
      found to be reduced after consecutive immobilization. Serum corticosterone levels
      were measured directly after a single and after 5 daily immobilization periods.
      After single immobilization the serum corticosterone level was found to be about
      270 ng/ml. After the 5th immobilization about 300 ng/ml were detected. These
      differences were not found to be significant. In summary, our data indicate that
      the serotonin metabolism shows habituation in nearly all brain areas after
      repeated immobilization, though the corticosterone level at the end of the
      immobilization period was comparable after single and repeated immobilization.

PMID- 9928884
TI  - Serotonin 5-HT3 receptor antagonists prevent cisplatin-induced emesis in
      Cryptotis parva: a new experimental model of emesis.
AB  - The aim of this manuscript is to introduce Cryptotis parva (the least shrew) as a
      new experimental emesis model. The chemotherapeutic agent, cisplatin, caused a
      dose-dependent increase in the number of animals exhibiting vomiting and retching
      behaviours with ED50 values of 6.43+/-1 and 7.9+/-1.2 mg/kg, respectively. The
      frequencies of these parameters were also dose-dependent. Intraperitoneal
      administration of 5-HT3 receptor antagonists (tropisetron or MDL 72222) prevented
      cisplatin-induced emesis and retching behaviours in the least shrew by a dose
      dependent mechanism with respective ID50 values of 4.28+/-2.8 and 2.05+/-2 for
      emesis, and 2.71+/-4.5 and 2.52+/-2.59 for retching. Intraperitoneal injection of
      selective and nonselective 5-HT3 receptor agonists potently, and in a dose
      dependent fashion, induced emesis in the least shrew with the following ED50
      potency order: 2-methyl 5-HT approximately 5-HT (p > 0.05) <5-HTQ (p < 0.01)
      <mCPBG (p < 0.001). As with other established experimental animal emesis models,
      the present data indicate that cisplatin causes emesis by activating 5-HT3
      receptors indirectly via release of 5-HT.

PMID- 9928887
TI  - Expression of a pulmonary endothelial norepinephrine transporter.
AB  - To determine whether pulmonary endothelial cells express the plasma membrane
      norepinephrine transporter (NET), an ovine-specific riboprobe was prepared from a
      partial NET cDNA clone isolated by PCR from a placental cDNA library. Northern
      hybridization detected a predominant 5.8 kb and a weaker transcript at 3.6 kb in
      RNAs isolated from near-term ovine fetal pulmonary endothelial cells. These data
      should be useful for future studies examining the molecular mechanisms underlying
      pulmonary endothelial NET expression and regulation.

PMID- 9928888
TI  - Changes in apparent in vivo binding of [3H]raclopride and [3H]N-methylspiperone
      induced by oxotremorine.
AB  - The effects of muscarinic agonist, oxotremorine (0.3 mg/kg), and antagonist,
      scopolamine (0.5 mg/kg), on in vivo [3H]raclopride (RAC) and [3H]N
      methylspiperone (NMSP) binding were investigated. Following tracer administration
      to control or pretreated mice, binding potentials, and the rate constants k3 and
      k4 were determined by kinetic analysis. Oxotremorine resulted in a 70% increase
      in striatal RAC binding potential compared with controls. RAC and NMSP showed
      almost identical decreases in k3 (40%), whereas k4 for RAC was unexpectedly
      decreased by 64%. Scopolamine resulted in no significant changes in RAC or NMSP
      binding. These results, in combination with previous data obtained in
      reserpinized mice, show that 1) competition by endogenous ligand may not be the
      only factor influencing the magnitude of apparent in vivo receptor binding, and
      2) interneuronal communication may be partly mediated by changes in the rates of
      ligand-receptor binding.

PMID- 9928889
TI  - PET studies of peripheral catechol-O-methyltransferase in non-human primates
      using [18F]Ro41-0960.
AB  - We previously reported the results of PET (positron emission tomography) studies
      of [18F]Ro41-0960, a potent COMT inhibitor, in baboon brain. Here we report an
      evaluation of the pharmacokinetics and specificity of binding of [18F]Ro41-0960
      in the peripheral organs of baboon. We observed a rapid clearance of the tracer
      from the heart and no significant uptake in the lung. In contrast, there was a
      high uptake and slow clearance in both kidney and liver, consistent with a high
      level of COMT in these peripheral organs. We also observed a dose-dependent
      inhibition of [18F]Ro41-0960 uptake by unlabeled Ro41-0960 (ED50 was 0.5 mg/kg in
      liver, and <0.01 mg/kg in kidney), with a halftime for recovery of COMT of about
      25 h at the dose of 2 mg/kg of unlabeled Ro41-0960. This indicates a reversible
      tight binding interaction between COMT and Ro41-0960 in both liver and kidney and
      suggests that [18F]Ro41-0960 may be a useful radiotracer for future examination
      of the functional activity of COMT in the human body.

PMID- 9928890
TI  - [123I]beta-CIT and SPECT in essential tremor and Parkinson's disease.
AB  - Resting and postural tremor may occur in essential tremor (ET) and Parkinson's
      disease (PD). The aim of the present study was to investigate the cocaine
      derivative [123I]beta-CIT, which labels striatal dopamine transporters, and SPECT
      in differentiating these diseases. METHODS: 30 healthy volunteers, 32 patients
      with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were
      investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1)
      were calculated for the striatum, the caudate nucleus and the putamen separately
      as well as a ratio putamen/caudate and the percent deviation of each patient's
      ratio from age-expected control values. RESULTS: Striatal [123I]beta-CIT binding
      ratios in ET were within normal ranges and showed only a discrete elevation to
      age-expected control values (+14.6%). In PD significantly reduced specific
      binding was evident not only contralaterally to the clinically affected side
      (putamen: -62%, caudate nucleus: -35%), but also ipsilaterally (putamen: -45%,
      caudate nucleus: -22%). All investigated parameters differed significantly
      between PD and controls and ET respectively. CONCLUSION: Imaging striatal
      dopamine transporters with [123I]beta-CIT and SPECT could clearly distinguish
      between ET and PD in an early stage of the disease. Findings do not suggest a
      subclinical involvement of dopaminergic nigrostriatal neurons in ET.

PMID- 9928891
TI  - Amantadine attenuates response alterations resulting from repetitive L-DOPA
      treatment in rats.
AB  - It has been shown that NMDA receptor antagonists can inhibit both the development
      and expression of a decrease in the duration of L-DOPA action in rats rotating
      after unilateral lesion of the nigro-striatal dopaminergic system. Using this
      model we found that the low affinity NMDA receptor antagonist amantadine (50
      mg/kg b.i.d.) attenuated both the expression and development of the shortening of
      duration of L-DOPA (25 mg/kg b.i.d.) action. Amantadine was most efficient when
      given both during the induction and expression phase. However, an additional
      interaction experiment demonstrated that acutely given amantadine also prolongs
      the duration of L-DOPA-induced rotations. Hence, only the effect on development
      of shortening of L-DOPA action can be regarded as specific for repetitive
      treatment mode. The data suggest that treatment with amantadine might have
      beneficial effects on response fluctuations produced by chronic L-DOPA treatment.

PMID- 9928892
TI  - Transient increase of pancreatic enzymes evoked by apomorphine in Parkinson's
      disease.
AB  - In one of our first patients with severely disabling and fluctuating Parkinson's
      disease (PD) we observed a transient pancreatic enzymes increase 6 months after
      continuous apomorphine therapy. Since this adverse effect had not been previously
      reported, we systematically investigated the course of pancreas and liver
      functions in response to apomorphine: laboratory and neurological assessments
      were conducted before initiation of apomorphine therapy, during the increment
      phase up to the optimal motor effective level and at all follow-up visits. We
      found in five out of 29PD patients a transient increase of pancreatic enzymes
      during the initial phase of continuous subcutaneous apomorphine application.
      Peaks of pathological plasma levels were apparent from the first day up to the
      fifth day after apomorphine initiation, and returned to normal levels within 10
      days in all 5 patients. Otherwise, this pancreatic enzymes increase was not
      accompanied by any raising in plasma levels of corresponding liver enzymes. No
      pathological signs in the endoscopic-retrograde cholangiopancreatography, the
      abdominal ultrasonography and the computed tomography of the abdomen were found
      in any of the affected PD patients. Furthermore, there was no evidence of
      pancreato-hepatal risk factors in the previous history in any of the PD patients
      studied. With respect to the course of PD, no differences were obtained upon
      comparison of affected and non-affected PD patients. Considering the patients'
      history, clinical course and current knowledge about the effect of apomorphine on
      pancreato-hepatal function, we conclude that a possible cumulative pathomechanism
      between transient pancreato-hepatal enzymes and continuous applied apomorpine,
      especially in the titrating phase, might cause this adverse event in about 20% of
      PD patients treated with apomorphine continuously.

PMID- 9928895
TI  - Environmental MPTP as a factor in the aetiology of Parkinson's disease?
AB  - The possibility that parkinsonism might be caused by environmental MPTP present
      in soot formed from partial combustion of coal has been assessed. Soot was
      fractionated and the bases were examined by gas chromatography-mass spectrometry
      (GC-MS) for 1,2,3,6-tetrahydro-1-methyl-4-phenylpyridine (MPTP). Although this
      method was considered to be capable of detecting MPTP in soot at about 1 in 10(
      6) its presence was not detected.

PMID- 9928894
TI  - Oxidation of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine, a 1-amino analog of
      MPTP, by type A and B monoamine oxidase.
AB  - A 1-amino analog of MPTP, 1(N)-amino-4-phenyl-1,2,3,6-tetrahydropyridine, was
      synthesized and the oxidation was examined using human synaptosomal mitochondria
      as sources of type A and B monoamine oxidase. An oxidation product, 1-amino-4
      phenylpyridinium ion, was quantified by high-performance liquid chromatography
      fluorometric detection. The amino analog was a substrate of both type A and B
      monoamine oxidase and the oxidation depended linearly on the enzyme amount and
      the reaction time with an optimal pH around 7.5. After the systemic injection of
      the amino analog in C57/black mice for one week, 1-amino-4-phenylpyridinium ion
      was detected in the brain. 1(N)-Amino-4-phenyl-1,2,3,6-tetrahydropyridine was
      proved to be cytotoxic to pheochromocytoma PC12 cells, and it may be a new
      neurotoxin bioactivated through the oxidation by type A and B monoamine oxidase.

PMID- 9928893
TI  - Cerebrospinal fluid selenium and chromium levels in patients with Parkinson's
      disease.
AB  - We compared CSF and serum levels of selenium and chromium, measured by atomic
      absorption spectrophotometry, in 28 patients with Parkinson's disease (PD) and 43
      matched controls. The CSF and serum levels of these trace metals did not differ
      significantly between PD patients and controls. CSF selenium and chromium levels
      were not correlated with age, age at onset, duration of the disease, scores of
      the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the
      PD group. Although antiparkinsonian therapy did not influence significantly the
      CSF levels of selenium, PD patients not treated with levodopa had significantly
      higher CSF selenium levels than controls (p < 0.01). It is possible that
      increased CSF selenium levels could indicate an attempt of protection against
      oxidative stress. The normality of CSF and serum chromium levels suggest that
      these values are not related with the risk for PD.

PMID- 9928896
TI  - Streptozotocin increases free fatty acids and decreases phospholipids in rat
      brain.
AB  - Streptozotocin (STZ) is a diabetogenic drug that disrupts glucose and energy
      metabolism in brain. To study its effect on brain lipids, tissue concentrations
      of free fatty acids and phospholipids were measured in the temporal cortex and
      the hippocampus of adult rats 3 weeks after a single intracerebroventricular
      (icv) injection of STZ. STZ increased concentrations of palmitic acid and stearic
      acid in temporal cortex and these of arachidonic acid both in the anterior part
      of the hippocampus and in CA1. In addition, palmitic acid and stearic acid
      concentrations were elevated in the anterior hippocampus. In contrast, STZ
      decreased brain cortex levels of phosphatidylethanolamine and phosphatidylserine.
      These data show that STZ alters brain lipid metabolism. They suggest that
      oxidative phospholipid breakdown is accelerated by STZ. These changes may be
      related to decreased brain glucose utilization and energy formation.

PMID- 9928897
TI  - The cerebrospinal fluid oxidized NO metabolites, nitrite and nitrate, in
      Alzheimer's disease and vascular dementia of Binswanger type and multiple small
      infarct type.
AB  - The concentration of the nitric oxide (NO) metabolites nitrite (NO2-) and nitrate
      (NO3-) in the cerebrospinal fluid from patients with Alzheimer's disease (AD),
      vascular dementia of the Binswanger type (VDBT) or multiple small infarct type
      (MSID), and controls were determined using high performance liquid
      chromatography. The nitrite concentration was significantly higher in VDBT/MSID
      patients than in controls (p < 0.005). The nitrate concentration and the combined
      nitrite and nitrate concentration was significantly higher in both AD (p < 0.05)
      and VDBT/MSID (p < 0.001) patients than in controls, with these concentrations
      being significantly greater in VDBT/MSID than AD patients (p < 0.005). The
      combined nitrite and nitrate concentration significantly decreased as the
      severity of dementia progressed in AD (rs=0.70, p < 0.01), but remained elevated
      in all stages of VDBT/MSID. These results suggest that NO production or oxidation
      in the brain increases in the early stage of AD and then decreases as neuronal
      cell loss progresses, but increases throughout the course of disease in
      VDBT/MSID, which may in part contribute to neuronal degeneration in both
      conditions.

PMID- 9928898
TI  - Erythrocyte and brain methionine adenosyltransferase activities in patients with
      schizophrenia.
AB  - The activity of methionine adenosyltransferase (MAT) was investigated in
      erythrocytes and postmortem brain specimens (cortex gyrus frontalis, hippocampus
      and thalamus) of patients with schizophrenia treated with neuroleptics. In
      comparison with the control group, abnormally low values of MAT Vmax and an
      increased MAT affinity towards methionine (lower Km values) were found in
      erythrocytes. In the brain, a regionally selective decrease of MAT Km was found
      in cortex gyrus frontalis but the Vmax values were however, unchanged. In the
      regions of cortex gyrus frontalis and hippocampus, but not in thalamus, the
      values of Vmax and Km were inversely correlated with the duration of
      schizophrenia. In rats treated for 28 days with the typical neuroleptic
      haloperidol and the atypical clozapine, a significant increase of MAT activity
      was found in the corpus striatum. There is the possibility that the changes
      observed in MAT activity in patients with schizophrenia are attributed to the
      neuroleptic medication.

PMID- 9928899
TI  - Neurochemical and behavioral evidence supporting (+)-AJ 76 as a potential
      pharmacotherapy for cocaine abuse.
AB  - In vivo microvoltammetry was used to detect synaptic concentrations of dopamine
      (DA) and serotonin (5-HT) from nucleus accumbens (NAcc) in awake, freely moving,
      male, Sprague Dawley laboratory rats, while their locomotor behavior was
      monitored, simultaneously, in an open-field paradigm; the purpose was to evaluate
      the pharmacology of the D3-preferring, dopamine (DA) autoreceptor antagonist, (+)
      AJ 76 [cis-(+)-1S, 2R-5-methoxy-1-methyl-2-(n-propylamino)-tetralin HCL] and its
      potential use as a pharmacotherapy for cocaine abuse. Results showed that (1).
      (+)-AJ 76 significantly increased synaptic concentration of DA above baseline (p
      < 0.001); a small but significant decrease in synaptic concentration of 5-HT was
      seen (p < 0.001), although a significant increase occurred during the time
      course, at the 20 minute mark (p < 0.05). Analysis of the two hour data also
      showed that both locomotor and central locomotor activity were not affected;
      however, temporally related increases in both behaviors were significant at 10,
      20 and 30 minutes (p < 0.05). In a second and separate study, (2). cocaine
      increased synaptic concentrations of DA (p < 0.001) and 5-HT (p < 0.001), and
      locomotor activity (p < 0.001) above baseline, but central locomotion was not
      affected, except for specific temporal enhancements at 10, 20, 30, 50, 60 and 90
      min. (p < 0.05). In a third and separate study, (3). an (+)-AJ 76/cocaine study,
      (+)-AJ 76 was administered five minutes before cocaine. The results showed that
      synaptic DA concentration was significantly increased over baseline values (p <
      0.001) but that synaptic DA was lower than cocaine-induced synaptic DA (p <
      0.001). No significant difference in synaptic 5-HT occurred after (+)-AJ
      76/cocaine treatment, but temporally related increases over baseline occurred
      from 10 to 40 min. (p < 0.05). Synaptic 5-HT concentrations after (+)-AJ
      76/cocaine were not significantly different from those induced by cocaine per se.
      (+)-AJ 76/cocaine treatment significantly increased locomotor activity (p <
      0.001); central locomotor behavior was not affected, however, time course data
      showed significant increases at 10, 20, 40, 50 and 80 min. (p < 0.05). The major
      finding from the present studies, is that +(-) AJ 76/cocaine treatment produced
      synaptic concentrations of DA from NAcc which were lower than those due to
      cocaine per se, while no differential effect on synaptic 5-HT concentration,
      locomotor or central locomotor behavior occurred. Therefore, these data support
      the hypothesis that (+)-AJ 76 may be useful for the treatment of cocaine
      addiction or abuse.

PMID- 9928900
TI  - Increased benzodiazepine receptor density in the prefrontal cortex in patients
      with panic disorder.
AB  - There are published studies concerning a regionally changed function of GABA
      benzodiazepine-receptor-complexes in anxiety disorder. These studies implicate
      the limbic lobe, the brainstem and the prefrontal cortex. Using 123I-Iomazenil
      and single photon emission tomography (SPET) we investigated the benzodiazepine
      receptor density in twelve patients with panic disorder who had never been
      treated with benzodiazepines before. Nine age- and sex-matched volunteers who
      were free of mental illness served as controls. Patients with panic disorder
      showed a significant increase of benzodiazepine receptor binding in the right
      supraorbital cortex and a trend to an increased uptake in the right temporal
      cortex. There was no correlation between receptor density and scores on
      Spielberger's State Trait Anxiety Inventory in the patient group. Since the
      findings cannot be explained by benzodiazepine exposure we hypothesize an
      upregulation due to functional or neuroanatomic changes (at least) in the
      frontotemporal cortex.

PMID- 9928901
TI  - Hyperactivity of hypothalamic pituitary axis in neonatal clomipramine model of
      depression.
AB  - This study examined the integrity of hypothalamic-pituitary-adrenal (HPA) axis in
      clomipramine model of depression. Male rat pups were treated twice daily from
      postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.). At three months of age,
      serum corticosterone level was estimated before and after dexamethasone (100
      microg/kg, s.c.) administration and after subjected to REM sleep deprivation
      (RSD) for 4 days consecutively. Data indicated enhanced baseline corticosterone
      levels and nonsuppression to dexamethasone in clomipramine treated rats. The
      corticosterone levels however, reversed to the levels of control group in rats
      subjected to RSD. These findings thus indicated for the first time an HPA
      hyperactivity in rats treated with clomipramine during neonatal period and are in
      harmony with cholinergic hypersensitivity reported earlier in this model of
      depression.

PMID- 9928902
TI  - Cloning and functional characterization of the human norepinephrine transporter
      gene promoter.
AB  - The norepinephrine transporter (NET) plays a critical role in brain
      norepinephrine homeostasis and is a target for antidepressants and drugs of
      abuse. We have analyzed the 5'-flanking regulatory region of the human NET gene
      (SLC6A2). Primer extension and 5' RACE revealed a single transcription start
      site, alternative splicing of exon 1 due to alternate splice donor usage, and a
      variable splice acceptor of intron 1. A TA-rich motif 35 bp upstream of the
      transcription start and several potential binding sites for transcription factors
      including a cAMP response element (CRE)-like motif are present in the 5'-flanking
      region. A 4.0-kb fragment, which had been fused to the luciferase reporter gene
      and transiently expressed in a NET+ cell line, displayed both constitutive and
      inducible promoter activity. Functional analysis by serial deletions revealed
      several clusters of cell-selective enhancer elements. Our findings indicate that
      (1) the NET gene promoter is active in NET-expressing cells and the information
      contained within approximately 4 kb of the 5'-flanking sequence is required to
      confer its cell-selective expression, (2) the expression of NET is regulated by a
      combination of positive cis-acting elements operating through a basal promoter
      defined by a TA-rich motif, and (3) the promoter responds to cAMP-dependent
      induction. Fusion of the human NET gene promoter to selected genes will
      facilitate their cell-selective expression in gene transfer strategies.

PMID- 9928904
TI  - Epithalamus calcifications in schizophrenia.
AB  - We evaluated the prevalence and the size of epithalamus calcifications (EC) and
      choroid plexus calcifications (CPC) on computed tomography (CT) scans in a group
      of 64 schizophrenic patients and in a group of 31 healthy controls. The
      associations between cerebral calcifications, demographic variables, and other
      brain morphological characteristics (particularly cerebral ventricular size and
      cortical atrophy) in both, patients and controls, were also considered. A
      significant increase in size of the epithalamic-region calcifications in
      schizophrenic patients was found, whereas there was no evidence of increase in
      both, dimension and prevalence, of choroid plexus calcification. Such dimensional
      increase was unrelated to the duration of illness and therefore did not seem to
      be iatrogenic or secondary to the disease. A correlation was found between
      epithalamus calcifications and cortical atrophy and third-ventricle enlargement,
      suggesting that calcifications of this cerebral region may be associated with
      lesions of third-periventricular areas and of circuitries hypothesized to be
      involved in the pathophysiology of schizophrenia.

PMID- 9928903
TI  - Prevalence of somatoform disorders in a psychiatric population: an Italian
      nationwide survey. Italian Collaborative Group on Somatoform Disorders.
AB  - The survey involved 50 centres comprising both hospital and community psychiatric
      care services throughout Italy. Overall, 2620 patients were recruited, and of
      those 2002 (76%) completed the Somatoform Disorders Schedule (SDS), a CIDI
      derived interview. The NOS somatoform disorders (SDs) diagnosis appeared to be
      the most common (60%) (and they showed the highest number of co-morbid
      diagnoses), followed by pain disorders (8%). The prevalence of undifferentiated
      somatoform and hypochondriactal disorders was 1.6%: older age groups showed a
      tendency towards higher rates of the latter. In general, the study found that a
      significant percentage of patients with SDs are referred to psychiatric services,
      but mainly because of other psychopathological problems: in fact, somatic
      complaints are cross-sectionally present in different psychiatric nosological
      categories. This study also emphasizes some limitations of the current
      classification of SDs.

PMID- 9928905
TI  - Reliability and validity of the premorbid adjustment scale (PAS) in a German
      sample of schizophrenic and schizoaffective patients.
AB  - Premorbid functioning seems to be a phenomenological marker that possibly
      distinguishes a subtype of schizophrenia. The Premorbid Adjustment Scale (PAS) is
      an instrument for measuring premorbid functioning. It has gained international
      acceptance, although little is known about the reliability and validity of the
      test. Here data on the reliability and validity of the test derived from a German
      sample of schizoaffective and schizophrenic subjects (n = 86) and their healthy
      parents (n = 38) is presented. The DSM-IV diagnosis, PAS and Positive and
      Negative Syndrome Scale (PANSS) data were used as well as data on the course of
      the disorder. The estimation of the reliability per scale by internal consistency
      showed high positive values of Cronbach's alpha between 0.809 and 0.931. High
      scores in PAS representing a bad premorbid social adjustment correlated
      significantly with a low age of onset, high PANSS scores, an insidious onset and
      a long period of hospitalisation. The disorganised DSM-IV subtype of
      schizophrenia showed a trend towards higher mean PAS scores. In the presented
      sample, the threshold between schizophrenics and healthy individuals is at 0.23.
      The PAS values higher than 0.53 appeared in patients with an unfavourable course
      of the disorder. These findings correspond with previous reports in the
      literature.

PMID- 9928907
TI  - 31P magnetic resonance spectroscopy in the frontal lobe of major depressed
      patients.
AB  - Most research with 31P-magnetic resonance spectroscopy (31P-MRS) in affective
      disorders has been done in the field of bipolar disturbances. Reduced frontal and
      temporal lobe phosphomonoester (PME) concentrations were measured in the euthymic
      state, whereas increased values were found in the depressed state. In bipolar-II
      patients reduced phosphocreatine (PCr) concentrations were reported in the
      euthymic, depressed, and manic state. The aim of the present study was to explore
      whether PME and PCr were also altered in the frontal lobe of major depressed,
      unipolar patients. Therefore, we used 31P-MRS to investigate the relative
      phospholipid and high-energy phosphate concentrations in the frontal lobe of 14
      unipolar patients, mostly medicated, and 8 age-matched controls. We found
      increased PME and decreased ATP values. Other 31P-MRS parameters were not
      different in both groups. Phosphomonoester percentages correlated negatively with
      the degree of depression. Thus, the main alterations found in bipolar depressed
      patients could also be demonstrated in unipolar depressed patients. The results
      are discussed with regard to disturbed phospholipid and intracellular high-energy
      phosphate metabolism in depressed patients.

PMID- 9928908
TI  - Antidepressant-associated maniform states in acute treatment of patients with
      bipolar-I depression.
AB  - Medical records of 158 patients with bipolar depression were analysed for the
      incidence of a switch from depression to maniform states (mania and hypomania).
      Relation to psychopharmacological treatment was investigated. Thirty-nine (25%)
      patients of the total sample had switched to a maniform state during the
      treatment period in the hospital. Among that group the phenomenon occurred in 23
      patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with
      a switch were significantly more often treated with tricyclic antidepressants
      (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication
      might reduce the risk for switching, especially in patients treated with TCA;
      however, it seems not totally sufficient, since 59% of the switched patients
      received mood stabilisers. The switch phenomenon was not associated with
      sociodemographic or clinical data.

PMID- 9928906
TI  - Autoantibodies against 60-kDa heat shock protein in schizophrenia.
AB  - Immunological abnormalities in schizophrenic patients have been reported for many
      years. However, the question of whether these parameters are involved in the
      pathophysiology of the disorder or represent treatment effects is still not
      answered. We investigated a combination of humoral and soluble immune parameters
      in 30 unmedicated schizophrenic patients before and during antipsychotic
      treatment and in 31 healthy controls. The aim of our study was to unravel an
      underlying immune process, to elucidate the influence of neuroleptic treatment
      and to identify a subgroup of schizophrenics. Antibodies against human 60-kDa
      heat-shock protein (HSP60), serum levels of soluble ICAM-1 and IL-2R were
      determined and correlated with parameters of blood-brain barrier and of
      psychopathology. In 10% of the drug-free but in 20% of the medicated
      schizophrenics, especially in females, we observed immunoreactivity against
      HSP60, high levels of IgG in CSF and a blood-brain barrier impairment. The high
      HSP antibody titres correlated with high levels of sIL-2R and sICAM-1. Only one
      of the controls showed antibodies against HSP60. Our results suggest that the
      observed immunological alterations are more pronounced during neuroleptic
      treatment than in the drug-free state. Whether or not this differential response
      to treatment with altered antibody production represents a subgroup of patients
      has yet to be determined.

PMID- 9928909
TI  - Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a
      confirmation in drug-free patients and correlation with white matter
      hyperintensity.
AB  - The authors have previously reported decreased intracellular pH (pHi) in the
      frontal lobes in euthymic bipolar patients treated with lithium using 31P-MRS.
      White matter hyperintensity (WMHI) is frequently seen in bipolar disorder. To
      examine a possible effect of lithium on pHi and the relationship between pHi and
      WMHI, seven drug-free euthymic bipolar patients were examined, and T2-weighted
      MRI were examined in 14 previously reported bipolar patients. Drug-free patients
      showed significantly lower pHi than controls. WMHI was associated with low pHi
      and increased phosphodiester peak. These results suggest that decrease of pHi is
      not an effect of lithium but is instead related to the pathophysiology of
      illness. Decrease of pHi and increase of the PDE peak may be the biochemical
      basis of WMHI in bipolar disorder.

PMID- 9928910
TI  - Markers from event-related potential subcomponents and reaction time for
      information processing dysfunction in schizophrenia.
AB  - Event-related potentials (ERPs) can serve as markers for cognitive processing
      stages. Identification of those ERPs altered in schizophrenia offer information
      about cognitive dysfunction. Auditory evoked potentials (AEPs) were elicited
      within an oddball paradigm in 35 schizophrenic patients and compared with 35
      healthy controls. N100 and P200, as well as N200, frontal P300 and parietal P300
      subcomponents, were separated using dipole source analysis. The amplitudes of the
      N100 and the parietal P300 measured in schizophrenics were diminished. The input
      related processing stages (N100 and P200) were not altered, whereas later, the
      deviant and task-related processes (N200, frontal P300, parietal P300 and
      reaction time) were significantly prolonged in schizophrenia.

PMID- 9928911
TI  - Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not
      predispose to schizophrenia.
AB  - The tuberous sclerosis complex (TSC) is an autosomal dominant disorder
      characterized by the development of malformations in various organs including the
      brain. A polymorphism in the TSC2 gene has been found to be increased in
      gangliogliomas, a lesion which is associated with disturbed neuro-glial cell
      migration pattern. Since these pathomorphological changes are compatible with
      disturbed neuronal migration in schizophrenic brains, we investigated this
      polymorphism in 130 families with a schizophrenic index patient. A 222-bp
      fragment of genomic DNA containing the TSC2 variant was analyzed by SSCP. The
      analysis revealed that there is no association with schizophrenia.

PMID- 9928913
TI  - Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid
      is a dopamine uptake inhibitor.
AB  - The antimicrobial agent oxolinic acid, injected i.p. in mice, induced a dose
      dependent increase in locomotor activity. This stimulation culminated at the 32
      mg/kg dose and became smaller for higher doses (64-128 mg/kg). When opposed to
      increasing doses (50-100-200 microg/kg i.p.) of haloperidol (D2 dopamine receptor
      antagonist), the stimulant locomotor effect of 32 mg/kg oxolinic acid was not
      significantly reversed. On the contrary increasing doses (7.5-15-30 microg/kg
      s.c.) of SCH 23390 (D1 dopamine receptor antagonist) inhibited the stimulant
      locomotor effect. In mice made completely akinetic by a pretreatment with
      reserpine (4 mg/kg s.c., 18 h before testing), dexamphetamine (2 mg/kg s.c.)
      reversed this akinesia and even displayed a stimulant activity, similar to that
      observed in mice not treated by reserpine. On the contrary, oxolinic acid (32
      mg/kg) did not reverse the reserpine induced akinesia and even opposed the
      reversion induced by dexamphetamine. In a synaptosomal fraction prepared from
      striatum of rats, oxolinic acid inhibited the 3H dopamine uptake with an IC50 =
      4.3+/-0.6 x 10(-6) M. Finally, in mice injected i.v. with a tracer dose of 3H WIN
      35428 (1 microCi) (a dopamine uptake blocker), 32 mg/kg oxolinic acid, i.p.
      administered, reduced by about 50% the specific binding of the radioligand to
      striatal dopamine carriers. It is concluded that the stimulant locomotor effect
      of oxolinic acid depends on the blockade of the neuronal dopamine uptake complex.

PMID- 9928912
TI  - Prediction of posttraumatic stress disorder by immediate reactions to trauma: a
      prospective study in road traffic accident victims.
AB  - Road traffic accidents often cause serious physical and psychological sequelae.
      Specialists of various medical faculties are involved in the treatment of
      accident victims. Little is known about the factors which might predict
      psychiatric disorders, e.g. Posttraumatic Stress Disorder (PTSD) after accidents
      and how psychological problems influence physical treatment. In a prospective
      study 179 unselected, consecutively admitted road traffic accident victims were
      assessed a few days after the accident for psychiatric diagnoses, severity of
      injury and psychopathology. All were inpatients and had to be treated for bone
      fractures. At 6-months follow-up assessment 152 (85%) of the patients were
      interviewed again. Of the patients, 18.4% fulfilled the criteria for
      Posttraumatic Stress Disorder (DSM-III-R) within 6 months after the accident.
      Patients who developed PTSD were injured more severely and showed more symptoms
      of anxiety, depression and PTSD a few days after the accident than patients with
      no psychiatric diagnosis. Patients with PTSD stayed significantly longer in the
      hospital than the other patients. Multiple regression analysis revealed that the
      length of hospitalization was due mainly to a diversity of factors such as
      severity of injury, severity of accident, premorbid personality and
      psychopathology. Posttraumatic stress disorder is common after road traffic
      accidents. Patients with PTSD at follow-up can be identified by findings from
      early assessment. Untreated psychological sequelae such as PTSD cause longer
      hospitalization and therefore more costs than in non-PTSD patients.

PMID- 9928914
TI  - The discriminative stimulus properties of U50,488 and morphine are not shared by
      fedotozine.
AB  - Fedotozine is a kappa opioid receptor agonist having antinociceptive properties
      but devoid of diuretic effects. The aim of the study was to evaluate the
      discriminative stimulus effects of fedotozine at doses previously reported to
      produce maximal effects in in vivo assays measuring kappa-mediated analgesia. By
      using a two-lever drug discrimination task, two groups of rats were trained to
      discriminate either a 3 mg/kg i.p. dose of the kappa opioid agonist, U50,488, or
      a 5 mg/kg i.p. dose of the mu opioid agonist, morphine, from saline. Once
      trained, rats were used to conduct tests of stimulus generalization with
      morphine, U50,488 and fedotozine along with another kappa agonist, CI-977, and
      another mu agonist, fentanyl. The stimulus effect of U50,488 was shared by CI-977
      but not by morphine. Conversely, the stimulus effect of morphine was shared by
      fentanyl but not by U50,488. Fedotozine (1-10 mg/kg) failed to substitute to
      either U50,488 or morphine. These results indicate that, when administered at
      doses fully effective in producing antinociception, the interoceptive stimulus
      effects of fedotozine, if any, can be distinguished from those produced by
      U50,488 and morphine.

PMID- 9928915
TI  - Effects of lithium treatment on extracellular serotonin levels in the dorsal
      hippocampus and wet-dog shakes in the rat.
AB  - In the present study wet-dog shakes in rats were induced by local potassium (K+)
      depolarization in the dorsal hippocampus. Concurrently, changes in extracellular
      concentrations of cyclic AMP (cAMP) and serotonin (5-HT) were assessed by
      microdialysis. It has been well-established that lithium influences the synthesis
      of cAMP in the brain via effects on adenylate cyclases. In this study, the effect
      of chronic lithium treatment on the number of wet-dog shakes and the release of 5
      HT was investigated. Wet-dog shakes, formation of cAMP and release of 5-HT were
      induced by perfusing a Ringer solution containing 60 mM K+ through the
      microdialysis probe for 20 min. Under some conditions, this high K+ solution also
      contained 20 microM forskolin. The number of wet-dog shakes and the formation of
      cAMP induced by K+ depolarization were enhanced by forskolin, while the K+ 
      stimulated release of 5-HT was unaffected by forskolin. Chronic lithium
      treatment, yielding a plasma lithium level of 0.78+/-0.09 mmol/l, decreased the
      number of wet-dog shakes but did not affect the extracellular level of 5-HT in
      the dorsal hippocampus. Chronic lithium treatment may affect the serotonergic wet
      dog shake syndrome in the rat partly via the cAMP signalling system but does not
      seem to influence this syndrome by changing the release of 5-HT from nerve
      terminals in the dorsal hippocampus.

PMID- 9928916
TI  - Conventional and spectral power analysis of all-night sleep EEG after subchronic
      treatment with paroxetine in healthy male volunteers.
AB  - Paroxetine is a selective and potent serotonin reuptake inhibitor with reported
      antidepressant properties. Since changes in the regular sleeping pattern were
      described as side effects under treatment with paroxetine, the impact of the drug
      on the sleep architecture is of major interest. The present study addressed the
      question of subchronic effects of paroxetine medication (30 mg/day) in eight
      healthy male volunteers in a double blind, placebo-controlled crossover-design.
      Conventional sleep EEG parameters and additionally computed spectral power
      analysis based on FFT of 20-s time epochs in the delta, theta, alpha, beta and
      gamma frequency range for different sleep stages after 4 weeks of treatment were
      investigated. Subchronic paroxetine administration in healthy subjects led to a
      prolonged REM latency and a decrease in the number of REM phases, whereas sleep
      efficiency, total sleep time, sleep onset latency, number of awakenings, and
      awake during sleep period time were not altered by paroxetine medication.
      Moreover, we could not detect any alterations of the spectral power values in
      certain frequency bands during NREM or REM sleep following subchronic paroxetine
      medication.

PMID- 9928917
TI  - Schizophrenia: do we really need placebo-controlled studies?
AB  - OBJECTIVE: To investigate whether placebo control is necessary to prove efficacy
      in short-term studies in schizophrenia. DESIGN: This study compares the efficacy
      results of placebo-controlled studies versus positive controlled studies, that is
      controlled studies without a placebo control, in the short-term treatment of
      chronic schizophrenia. RESULTS: Concerning mean improvement on the BPRS, the
      placebo arms showed in two cases a worsening, in one case almost no change, and
      in the remaining studies (6) the improvement was between 1 and 5%. The percentage
      mean improvement in the haloperidol arms of the placebo-controlled studies was
      comparable to the percentage mean improvement in the corresponding arms of the
      non-placebo-controlled studies. The highest percentage responders in the placebo
      groups was 43% and the lowest was 6%. Moreover the responder rates in the
      atypical antipsychotic and haloperidol arms of the non-placebo-controlled studies
      were, in two of the three studies, in the same order of magnitude as the
      responder rates of the placebo arms in the placebo-controlled studies. The
      overall dropout rates in the placebo arms was between 48% and 80% and were higher
      than the drop out rates in the atypical neuroleptic arms and haloperidol arms of
      the placebo-controlled studies. The dropout rates due to an insufficient response
      in the atypical neuroleptic arms and haloperidol arms of the non-placebo
      controlled studies were lower when compared to corresponding treatment arms of
      the placebo-controlled studies. CONCLUSION: In contrast to the mean improvement
      on the BPRS, responder rates in the placebo arms varied considerably from study
      to study. Responder rates in the atypical antipsychotic and haloperidol arms of
      the non-placebo-controlled studies were, in two of the three studies, of the same
      order of magnitude as the responder rates of the placebo arms in the placebo
      controlled studies. These results indicate that placebo control is necessary.
      Moreover as responders are a more clinically relevant outcome measure when
      compared to mean improvement on a rating scale, placebo-controlled studies are
      still needed. However, consensus on responder definition should be agreed upon.
      For the moment, alternatives to placebo-controlled studies are inadequate in
      demonstrating efficacy in studies with schizophrenic patients.

PMID- 9928918
TI  - Caffeine place conditioning in rats: comparison with cocaine and ethanol.
AB  - The present study employed the place conditioning technique to compare rewarding
      potential of caffeine with that of cocaine and ethanol. In Experiment 1 caffeine,
      cocaine and ethanol place conditioning were estimated independently, whereas in
      Experiments 2 and 3 the preference of the external cues associated with caffeine
      vs. cocaine and caffeine vs. ethanol was assessed in a single test. Caffeine (1.5
      mg/kg, i.p.) cocaine (5 mg/kg, i.p.) and ethanol (1.2 g/kg, i.g.) did produce
      secondary reinforcing effects comparable in magnitude (Experiment 1). In
      Experiments 2 and 3 animals had the opportunity 'to compare' rewarding effects of
      two drugs. Data showed that the preference of cocaine-paired cues was absolutely
      (100%) higher than those of caffeine, whereas reinforcing actions of caffeine and
      ethanol seemed to be equal. The proposed modification of conditioned place
      preference procedure may be useful for the comparison of rewarding values of
      different drugs with presumed addictive potential.

PMID- 9928919
TI  - Intravenous self-administration of gamma-hydroxybutyric acid in drug-naive mice.
AB  - The reinforcing effects of gamma-hydroxybutyric acid (GHB) were studied by means
      of intravenous self-administration in drug-naive mice. GHB self-administration
      was concentration-dependent (0.01-0.5 mg/kg/inj.) according to a bell-shaped
      curve. Pretreatment with the specific GHB receptor antagonist NCS-382 at a dose
      of 12.5 mg/kg i.p. completely antagonized the reinforcing effects of GHB. These
      data suggest that GHB is able to induce reinforcing effects in mice and support
      the hypothesis of an abuse liability of this drug.

PMID- 9928920
TI  - Interaction between the tetracyclic antidepressant mianserin HCl and opioid
      receptors.
AB  - The antinociceptive effects of the tetracyclic antidepressant mianserin and its
      interaction with various opioid receptor subtypes was evaluated. Mice were tested
      with a hotplate analgesia meter. Mianserin elicited an antinociceptive effect in
      a dose-dependent manner following doses from 1-25 mg/kg. As the mianserin dose
      increased beyond 30 mg/kg, latencies returned to baseline, yielding a biphasic
      effect. This effect of mianserin was antagonized by naloxone (P<0.005), implying
      a possible opioid mechanism of action involved in the mianserin induced
      antinociceptive effect. When administered with various opioid antagonists, the
      sensitivity of mianserin to selective opioid antagonists was found significant
      for mu and kappa1 opioid receptor subtypes (P<0.005), but not for delta-receptor.
      At the next stage mianserin was administered together with various agonists of
      opioid receptors. When administered together with opiates, mianserin
      significantly potentiates analgesia at the mu, kappa1 and kappa3 opioid receptor
      subtype (P<0.005) and to a lesser extent, at the delta opioid receptors. These
      results suggest a potential use of mianserin in the management of some pain
      syndromes. However, further research is needed in order to establish both the
      exact clinical indications and the effective doses of mianserin when prescribed
      for pain.

PMID- 9928921
TI  - The speech analysis approach to determining onset of improvement under
      antidepressants.
AB  - In a study of 43 hospitalized depressive patients we investigated the course of
      recovery at a dense time resolution throughout the first two weeks of treatment.
      In addition to the assessment of the patients' psychopathology on the basis of
      HAMD and AMDP rating scales, speech recordings were carried out for each patient
      immediately before the psychiatric exploration. Our analyses yielded no evidence
      for a delayed onset of action of antidepressants. Onset of improvement occurred
      in the great majority of patients (79.1%) within the first 12 days of study,
      independently of the severity of depression at baseline. Early improvement was
      highly predictive of later outcome and could not be attributed to a few items, as
      score reductions were observed for virtually all HAMD items at very early stages
      of recovery. The analysis of the patients' speaking behavior and voice sound
      characteristics yielded in 62.8% of cases an essentially parallel development
      over time for the HAMD scores on the one hand, and acoustic variables on the
      other. In consequence, early improvement appears to have a biological background
      and is unlikely to be mainly attributable to the expectations of doctors and
      patients.

PMID- 9928922
TI  - Hyperresponsivity to nicotinic acid challenge in generalized social phobia: a
      pilot study.
AB  - Although blushing is an almost pathognomonic feature of social phobia, little is
      known about the neurobiology of blushing in this disorder. Nicotinic acid (100
      mg), a vasodilator that may induce flushing, was administered to six male
      patients with generalized social phobia and to six healthy male controls.
      Compared with controls, patients demonstrated increased flushing, anxiety,
      autonomic activity, and temperature after nicotinic acid administration. Further
      controlled research is necessary to confirm and extend these pilot findings.

PMID- 9928923
TI  - Combination treatment with clozapine and paroxetine in schizophrenia: safety and
      tolerability data from a prospective open clinical trial.
AB  - Clozapine is a drug with many side effects, some of them with potentially
      hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored.
      It has been shown that the metabolism of clozapine may be affected by concomitant
      treatment with selective serotonin reuptake inhibitors (SSRIs), while there have
      been reports of improved efficacy on negative symptomatology of clozapine in
      combination with SSRIs. Therefore, this prospective open clinical trial was
      performed to investigate the safety and tolerability of the coadministration of
      clozapine and paroxetine under control of serum concentrations of clozapine and
      its metabolites and the effect of this combination treatment on
      psychopathological outcome was evaluated. A total of 14 patients suffering from
      schizophrenia or schizodepressive disorder with predominant negative
      symptomatology were included. The duration of the study was at least 6 weeks for
      each patient. Initial treatment was a monotherapy with clozapine at a daily dose
      of 2.5 mg/kg weight. After two measurements of serum concentrations of clozapine
      and metabolites during steady state conditions, an add-on therapy with 20 mg
      paroxetine was initiated. No concomitant medication was allowed. The main finding
      of our prospective study was that addition of paroxetine to a monotherapy with
      clozapine was a well tolerated medication that did not give rise to new
      clinically relevant side effects. After addition of paroxetine the serum
      concentrations of clozapine and its major metabolites remained virtually
      constant. The results of the psychopathological measurements indicated a further
      clinical improvement, although the small open study could not test for efficacy.

PMID- 9928924
TI  - High doses of testosterone increase anticonflict behaviour in rat.
AB  - Male rats exposed to high levels of testosterone for 8 weeks, or to one high dose
      of testosterone 24 h before testing, displayed an increase in punished responding
      in the Vogel conflict test. The findings may be taken as indirect support for the
      assumption that the conflict paradigm reflects not only anxiety but also
      impulsivity.

PMID- 9928925
TI  - Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D
      agonist sumatriptan.
AB  - The serotonergic system has been implicated in both the aetiology and
      pharmacological treatment of obsessive compulsive disorder. In pharmacological
      challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT2C as well as
      5HT1A and 5HT1D receptors, was associated with a transient exacerbation of
      obsessive compulsive symptoms. Chronic administration of mCPP was found to bring
      about some relief of these symptoms. Sumatriptan is an antimigraine agent, which
      interacts most potently with 5HT1D receptors. In the cases to be presented, we
      report the effects of chronic administration of Sumatriptan to three severe,
      treatment resistant, OCD patients. Following chronic administration of
      sumatriptan, these patients, who have been resistant to any former
      pharmacological treatment, responded with an improvement in their depression and
      a modest reduction in their obsessive compulsive symptoms.

PMID- 9928927
TI  - National trends of research in neuroscience.

PMID- 9928926
TI  - "Atypical" neuromodulatory profile of glutapyrone, a representative of a novel
      'class' of amino acid-containing dipeptide-mimicking 1,4-dihydropyridine (DHP)
      compounds: in vitro and in vivo studies.
AB  - Glutapyrone, a disodium salt of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4
      dihydropyridine-4-carboxamido)- glutaric acid, is a representative of a novel
      'class' of amino acid-containing 1,4-dihydropyridine (DHP) compounds developed at
      the Latvian Institute of Organic Synthesis, Riga, Latvia. Conceptually, the
      glutapyrone molecule can be regarded as a dipeptide-mimicking structure formed by
      the "free" amino acid (glutamate) moiety and "crypto" (built into the DHP cycle)
      amino acid ("GABA") elements. Both of these amino acids are joined by the peptide
      bond. This compound unlike classical DHPs lacks calcium antagonistic or agonistic
      properties. Our previous studies revealed a profound and long-term
      anticonvulsant, stress-protective and neurodeficit-preventive activities of
      glutapyrone. In view of structural properties the role of glutamatergic
      mechanisms in the mediation of central effects of glutapyrone was considered. In
      the present study glutapyrone at the concentration range of 1 microM(-1) mM
      failed to effect both NMDA ([3H]TCP) and non-NMDA ([3H]KA and [3H]AMPA) receptor
      ligand binding in the rat cortical membranes in vitro. The compound markedly
      enhanced motor hyperactivity induced by the NMDA antagonist PCP and the dopamine
      releasing compound D-amphetamine in the rats. Glutapyrone displayed activity in a
      variety of animal models relevant for affective/depressive disorders in humans
      i.e. reserpine-induced ptosis and hypothermia, forced swimming test and open
      field test. These data indicate that the unusually "broad" pharmacological
      spectrum of glutapyrone might involve concomitant actions on multiple
      neurotransmitter systems, particularly, GABA-ergic and the catecholamines. It is
      discussed whether these functional properties are secondary to action on
      intracellular events, predominantly, G protein-related since glutapyrone appears
      to lack direct interactions with a number of receptors including ionotropic
      glutamate and GABA(A)/Bzd receptors.

PMID- 9928928
TI  - Missing action of carbamazepine on postsynaptic GABA-responses of hippocampal CA3
      neurons (slice, guinea pig).
AB  - Conflicting data exist concerning the interaction of carbamazepine (CBZ) and GABA
      receptors involved in the pathophysiology of neuropsychiatric disorders. The
      present study reveals that CBZ failed to alter membrane potential fluctuations
      mediated by an activation of postsynaptic GABA(A)- and GABA(B)-receptors of
      hippocampal CA3-neurons even at a bath concentration of 500 microM (ca. 10-30
      fold the therapeutic level, tested up to 90 min). Therefore, therapeutic effects
      of CBZ cannot be due to acute modulations of postsynaptic GABA-responses.

PMID- 9928929
TI  - Dynamic organization of the beta-heterochromatin in the Drosophila melanogaster
      polytene X chromosome.
AB  - Region 20 of the polytene X chromosome of Drosophila melanogaster was studied in
      salivary glands (SG) and pseudonurse cells (PNC) of otu mutants. In SG
      chromosomes the morphology of the region strongly depends on two modifiers of
      position effect variegation: temperature and amount of heterochromatin. It is
      banded in XYY males at 25 degrees C and beta-heterochromatic in X0 males at 14
      degrees C, i.e. it shows dynamic transitions. In PNC chromosomes region 20 is not
      heterochromatic, but demonstrates a clear banding pattern. Some molecular markers
      of mitotic heterochromatin were localized by means of in situ hybridization on
      PNC chromosomes: DNA of the gene su(f) in section 20C, the nucleolar organizer
      and 359-bp satellite in 20F. The 359-bp satellite, which has been considered to
      be specific for heterochromatin of the mitotic X chromosome, was found at two
      additional sites on chromosome 3L, proximally to 80C. The right arm of the X
      chromosome in SG chromosomes was localized in the inversion In(ILR)pn2b: the
      telomeric HeT-A DNA and AAGAG satellite from the right arm are polytenized,
      having been relocated from heterochromatin to euchromatin.

PMID- 9928930
TI  - Molecular characterization of HymA, an evolutionarily highly conserved and highly
      expressed protein of Aspergillus nidulans.
AB  - Aspergillus nidulans reproduces asexually via uninucleate, haploid spores, which
      are produced on morphologically differentiated aerial structures, called
      conidiophores. These consist of four distinct cell types, a foot with a
      terminally swollen stalk, metulae, phialides and conidiospores. The molecular
      mechanisms underlying the morphological changes that occur during conidiophore
      development have been studied by mutant analysis. We have isolated the hym A
      mutant, in which conidiophore development is affected at the metula stage. In the
      mutant metulae do not differentiate properly but come to resemble hyphae (hym =
      hypha-like metulae). In this paper we have analyzed the corresponding gene. It
      encodes a highly expressed 44 kDa protein which resides in the cytoplasm and has
      homologues in yeast, plants, fly, worm, fish, mice and man. We constructed hym
      deletion strains of Saccharomyces cerevisiae and of A. nidulans and found that
      the gene is essential in S. cerevisiae but is dispensable in the filamentous
      fungus. A cellular function for the Hym protein has not yet been defined in any
      organism. To demonstrate functional conservation we constructed a chimeric
      protein comprised of the N-terminal half of the A. nidulans and the C-terminal
      half of the mouse homologue MO25. This hybrid protein could fully substitute for
      HymA function in A. nidulans. In addition, the mouse protein itself partially
      rescued the hym A mutation in the fungus. HymA is thus highly conserved in
      evolution and probably serves similar functions. The fact that hym A is required
      for conidiophore development in A. nidulans suggests that homologous genes in
      other organisms might also be involved in morphogenesis.

PMID- 9928932
TI  - A human gene, hSGT1, can substitute for GCR2, which encodes a general regulatory
      factor of glycolytic gene expression in Saccharomyces cerevisiae.
AB  - To determine whether similar regulatory mechanisms control the expression of
      glycolytic genes in yeast and human cells, we screened a human brain cDNA library
      for clones which complement the growth defect of the gcr2 mutant of Saccharomyces
      cerevisiae, and isolated hSGT1 (human suppressor of GCR two). Further work
      confirmed that the rescue of growth was associated with recovery of glycolytic
      enzyme activities, and that hSGT1 did not complement the growth defect of a gcr1
      mutant. A hybrid protein comprising hSgt1p and the DNA-binding domain of Gal4p
      (GBD) activated a GAL1-lacZ reporter gene fusion, suggesting that the cloned gene
      may be a transcriptional activator. Two-hybrid experiments in yeast also indicate
      that hSgt1p interacts with Gcr1p. Northern analysis showed that hSGT1 is highly
      expressed in muscle and heart. Although the predicted amino acid sequence of
      hSgt1p does not display significant similarity to Gcr2p, we speculate that their
      functions may be analogous.

PMID- 9928933
TI  - The Saccharomyces cerevisiae protein YJR043C (Pol32) interacts with the catalytic
      subunit of DNA polymerase alpha and is required for cell cycle progression in
      G2/M.
AB  - We have analysed the YJR043c gene of Saccharomyces cerevisiae, previously
      identified by systematic sequencing. The deletion mutant (yjr043cdelta) shows
      slow growth at low temperature (15 degrees C), while at 30 degrees C and 37
      degrees C the growth rate of mutant cells is only moderately affected. At
      permissive and nonpermissive temperatures, mutant cells were larger and showed a
      high proportion of large-budded cells with a single duplicated nucleus at or
      beyond the bud neck and a short spindle. This phenotype was even more striking at
      low temperature, the mutant cells becoming dumbbell shaped. All these phenotypes
      suggest a role for YJR043C in cell cycle progression in G2/M phase. In two-hybrid
      assays, the YJR043c gene product specifically interacted with Pol1, the catalytic
      subunit of DNA polymerase alpha. The pol1-1 /yjr043cdelta double mutant showed a
      more severe growth defect than the pol1-1 single mutant at permissive
      temperature. Centromeric plasmid loss rate elevated in yjr043cdelta. Analysis of
      the sequence upstream of the YJR043c ORF revealed the presence of an MluI motif
      (ACGCGT), a sequence associated with many genes involved in DNA replication in
      budding yeast. The cell cycle phenotype of the yjr043cdelta mutant, the evidence
      for genetic interaction with Pol1, the presence of an MluI motif upstream and the
      elevated rate of CEN plasmid loss in mutants all support a function for YJR043C
      in DNA replication.

PMID- 9928931
TI  - The S/M checkpoint at 37 degrees C and the recovery of viability of the mutant
      poldeltats3 require the crb2+/rhp9+ gene in fission yeast.
AB  - We have isolated a mutant in fission yeast, in which mitosis is uncoupled from
      completion of DNA replication when DNA synthesis is impaired by a thermosensitive
      mutation in the gene encoding the catalytic subunit of DNA polymerase delta. By
      functional complementation, we cloned the wild-type gene and identified it as the
      recently cloned checkpoint gene crb2+/rhp9+. This gene has been implicated in the
      DNA damage checkpoint and acts in the Chk1 pathway. Unlike the deleted strain
      dcrb2, cells bearing the crb2-1 allele were not affected in the DNA repair
      checkpoint after UV or MMS treatment at 30 degrees C, but were defective in this
      checkpoint function when treated with MMS at 37 degrees C. We analysed the
      involvement of Crb2 in the S/M checkpoint by blocking DNA replication with
      hydroxyurea, by using S phase cdc mutants, or by overexpression of the mutant
      PCNA L68S. Both crb2 mutants were unable to maintain the S/M checkpoint at 37
      degrees C. Furthermore, the crb2+ gene was required, together with the cds1+
      gene, for the S/M checkpoint at 30 degrees C. Finally, both the crb2 deletion and
      the crb2-1 allele induced a rapid death phenotype in the poldeltats3 background
      at both 30 degrees C and 37 degrees C. The rapid death phenotype was independent
      of the checkpoint functions.

PMID- 9928934
TI  - The Saccharomyces cerevisiae RAD54 gene is important but not essential for
      natural homothallic mating-type switching.
AB  - Homothallic Saccharomyces cerevisiae strains switch their mating-type in a
      specific gene conversion event induced by a DNA double strand break made by the
      HO endonuclease. The RAD52 group genes control recombinational repair of DNA
      double strand breaks, and we examined their role in native homothallic mating
      type switching. Surprisingly, we found that the Rad54 protein was important but
      not essential for mating-type switching under natural conditions. As an upper
      limit, we estimate that 29% of the rad54 spore clones can successfully switch
      their mating-type. The RAD55 and RAD57 gene products were even less important,
      but their presence increased the efficiency of the process. In contrast, the
      RAD51 and RAD52 genes are essential for homothallic mating-type switching. We
      propose that mating-type switching in RAD54 mutants occurs stochastically with a
      low probability, possibly reflecting different states of chromosomal structure.

PMID- 9928935
TI  - The protease activity of a calpain-like cysteine protease in Saccharomyces
      cerevisiae is required for alkaline adaptation and sporulation.
AB  - Abstract Saccharomyces cerevisiae has only one putative gene (designated CPL1)
      for a cysteine protease with a protease domain similar to that of calpain. This
      gene product shows significant sequence similarity to PalBp, a fungal (Emericella
      nidulans) calpain-like protease that is responsible for adaptation under alkaline
      conditions, both in the protease domain and the domain following the protease
      domain. CPL1 disruptant strains show impaired growth at alkaline pH, but no
      obvious growth defects under acidic pH conditions. This phenotype is complemented
      by the wild-type CPL1 gene, and its protease activity is essential for
      complementation. Disruption of CPL1 also causes reduced sporulation efficiency
      and promotes the degradation of the transcription factor Rim101p, which is
      involved in the sporulation pathway and has been shown to accumulate in a C
      terminally truncated, active form under alkaline conditions. Furthermore,
      expression of the C-terminally truncated Rim101p suppressed the alkaline
      sensitivity associated with CPL1 disruption. These results indicate that a
      calpain-like cysteine protease, Cpl1p, plays an important role in alkaline
      adaptation and sporulation processes, via regulation of the turnover and
      processing of the transcription factor Rim101p.

PMID- 9928936
TI  - Directional cloning of native PCR products with preformed sticky ends (autosticky
      PCR).
AB  - A novel method for the directional cloning of native PCR products was developed.
      Abasic sites in DNA templates make DNA polymerases stall at the site during
      synthesis of the complementary strand. Since the 5' ends of PCR product strands
      contain built-in amplification primers, abasic sites within the primers result in
      the formation of 5' single-stranded overhangs at the ends of the PCR product,
      enabling its direct ligation to a suitably cleaved cloning vector without any
      further modification. This "autosticky PCR" (AS-PCR) overcomes the problems
      caused by end sensitivity of restriction enzymes, or internal restriction sites
      within the amplified sequences, and enables the generation of essentially any
      desired 5' overhang.

PMID- 9928937
TI  - Gene stability in transgenic aspen (Populus). I. Flanking DNA sequences and T-DNA
      structure.
AB  - The stability of transgenes in the genome of transformed plants depends strongly
      on their correct physical integration into the host genome as well as on flanking
      target DNA sequences. For long-lived species like trees, however, no information
      is available so far concerning inactivation or loss of transgenes due to gene
      silencing or somatic genome rearrangement events. In this study, four
      independently transformed 35S-rolC transgenic hybrid aspen plants (Populus
      tremula L. x tremuloides Michx.), each harbouring one copy of the transgene, were
      investigated during continuous growth in the greenhouse. In one of these
      transgenic lines (Esch5:35S-rolC-#1) individuals frequently show phenotypic
      reversions, while in the remaining three lines (Esch5:35S-rolC-#3, -#5, -#16) the
      gene was essentially stable. Molecular analysis including PCR, Southern and
      Northern assays clearly showed that the transgene had been lost in the revertant
      tissue of the unstable line. Sequencing of T-DNA right and left borders, and
      flanking DNA regions, in all four transgenic aspen lines revealed no differences
      either in the type of flanking DNA (G-C to A-T ratio) or with respect to the
      presence of enhancers or MAR (matrix associated repeats)-like structures. Primers
      located within the left and right flanking regions in the three stable lines
      could be used to recover the target sites from the untransformed plants. This was
      not possible, however, with the unstable line, indicating that at least one
      flanking sequence does not derive from the plant target DNA but is of unknown
      origin. PCR using other primer pairs, and inverse PCR analysis, revealed an
      additional truncated T-DNA copy of 1050 nucleotides adjacent to the left border
      of the complete copy in this line. Sequencing of this truncated T-DNA revealed
      that it represented an inverted copy of part of the right half of the original
      construct. This special feature would allow the inverted repeat to pair with
      right border sequences of the complete copy. This would explain the frequently
      observed reversion resulting in transgene loss as due to intrachromosomal base
      pairing leading to double-stranded loops of single-stranded DNA during mitotic
      cell divisions.

PMID- 9928938
TI  - Gene silencing results in instability of antibody production in transgenic
      plants.
AB  - The stability of antibody and Fab expression was assessed in five different
      homozygous transgenic Arabidopsis lines. Each of these lines showed silencing of
      the transgenes that encode the antibody polypeptides, leading to instability of
      antibody production. However, each line had a different and specific instability
      profile. The characteristic variation in the level of antibody accumulation in
      each line as a function of developmental stage indicated that the T-DNA
      integration pattern played a role in triggering silencing, and also that the
      history and the integration position of simple transgene loci can influence the
      susceptibility to epigenetic silencing. In different lines with low antibody
      accumulation levels, methylation was found either in the promoter alone, in both
      the promoter and the transcribed region, in the transcribed region only, or in
      the transcribed region and downstream sequences. In conclusion, our data suggest
      that epigenetic effects result in different transgene expression profiles in each
      of the five Arabidopsis lines analyzed.

PMID- 9928939
TI  - Identification and characterization of novel retrotransposons of the gypsy type
      in rice.
AB  - We found that two DNA fragments, which were obtained from Oryza sativa L cv. IR36
      by PCR using degenerate primers designed for amplification of a rice gene, showed
      homology with the rt gene encoding reverse transcriptase of the Drosophila
      retrotransposon gypsy. We named the element from which they originated RIRE3 (for
      rice retrotransposon No. 3) and analyzed it further by isolating various clones
      containing segments of RIRE3. Nucleotide sequencing of the clones revealed that
      RIRE3 has LTRs (2316 bp) and that the internal sequence (5775 bp) includes a
      large ORF with gag and pol regions; the pol region includes the rt gene as well
      as the int gene encoding integrase in this order, as in gypsy. Interestingly, the
      region upstream of gag in RIRE3 contained another open reading frame, here called
      orf0, which does not exist in gypsy or in other retrotransposons related to it.
      In the course of characterizing RIRE3, we obtained a further clone, which showed
      less homology with the pol region of RIRE3. This clone was found to be derived
      from another gypsy-type retrotransposon (named RIRE8) containing the LTR sequence
      and orf0 both of which were only weakly homologous to that in RIRE3. Further
      characterization of RIRE8 revealed that there were actually two subtypes of RIRE8
      (named RIRE8A and RIRE8B), which show little homology to each other in the orf0
      region. Although the LTRs of RIRE3 and RIRE8 elements show very weak homology
      with each other, there exists a conserved sequence at their termini. We therefore
      carried out PCR using primers which hybridize to the rt gene of RIRE3, and total
      genomic DNA from various monocot and dicot plants as templates, and found that a
      family of RIRE3 elements was present in all plants tested.

PMID- 9928940
TI  - Either of the chromosomal tuf genes of E. coli K-12 can be deleted without loss
      of cell viability.
AB  - A method of lambda-mediated gene replacement was used to disrupt tufA or tufB on
      the chromosome of the E. coli K-12 strain MG1655. Both tuf genes, which are
      almost identical but map in different chromosomal contexts, encode the essential
      peptide chain elongation factor EF-Tu, one of the most abundant cytoplasmic
      proteins. Southern analysis confirmed replacement of the chromosomal tufA or tufB
      gene by a chloramphenicol resistance marker, demonstrating that both tuf genes
      are individually dispensable for growth. Under conditions of rapid growth,
      deletion of tufB had no significant effect on growth rate, but deletion of tufA
      resulted in a 35% increase in generation time. In minimal medium we observed no
      negative effects of tufA deletion on growth rate. Strains with a single tuf gene
      are useful for the expression of mutant forms of EF-Tu as the sole species in
      cells; this was demonstrated by introducing the hybrid tufAhis gene, encoding EF
      TuA extended with a C-terminal (His)6 tag, into the chromosome of a strain
      lacking tufB.

PMID- 9928941
TI  - Transition metal ion-catalyzed oxygen activation during pathogenic processes.
AB  - Most pathological processes include the production of activated oxygen species
      augmented or attenuated by transition metal ions catalyzing one electron
      transitions. Inhalation of airborne particles, infections, ingestion of toxins or
      liberation from endogenous stores represent biological pathways for the induction
      of pathogenic processes by these metal ions. In this short review basic reactions
      involving transition metal ions operating during oxidative stress in certain
      diseases will be discussed.

PMID- 9928942
TI  - Identification of a splice variant of neutrophil collagenase (MMP-8).
AB  - We have identified a splice variant of human neutrophil collagenase (MMP-8)
      transcript (MMP-8alt) that has a 91 bp insertion between codons for amino acid
      residues 34 and 35 of MMP-8 cDNA. This splice variant encodes an open reading
      frame for a 444 residue protein, lacking a secretory signal sequence. Our data
      suggested that, as opposed to the original MMP-8, the translation product of MMP
      8alt is not a secreted protein; nevertheless, it is enzymatically active. Further
      studies aimed at identifying the physiological substrates of MMP-8alt protein may
      lead to uncover novel roles it plays in cellular physiology.

PMID- 9928943
TI  - Expression of functional Na+/H+ antiporters of Helicobacter pylori in antiporter
      deficient Escherichia coli mutants.
AB  - An open reading frame with a sequence homologous to Escherichia coli Na+/H+
      antiporter A (ENhaA) was found in the total genomic sequence of Helicobacter
      pylori, a pathogenic bacterium of gastric inflammation, and was named HNhaA. The
      primary sequences and the hydropathy profiles of ENhaA and HNhaA were very
      homologous except for one additional region found in HNhaA. This sequence has
      about 40 hydrophilic amino acid residues inserted at the position next to residue
      235 of ENhaA which corresponds to residue 245 of HNhaA. HNhaA was expressed in E.
      coli mutants deficient in Na+/H+ antiporters and complemented the salt-sensitive
      phenotype of the mutants. Membrane vesicles prepared from these transformants of
      HNhaA using mutants deficient in the antiporters had the antiporter activities.
      Surprisingly, the antiporter activity in the transformant membranes was high at
      acidic and neutral pH, while ENhaA did not function at these pHs. A hydrophilic
      region around residue 235 in ENhaA and the additional hydrophilic region of about
      40 residues in the same region found in HNhaA might be responsible for this
      difference in activity by acting as putative pH sensors.

PMID- 9928944
TI  - Application of fluorescence polarization to the steady-state enzyme kinetic
      analysis of calpain II.
AB  - This paper presents the application of fluorescence polarization to the
      determination of dissociation constants for competitive inhibitors that bind to
      enzymes. This steady-state enzyme kinetic study measures the inhibition of the
      conversion of a fluorescently tagged substrate to a lower molecular weight
      fluorescent product by calpain II. It relies on the measurement of a parameter
      proportional to velocity, which is sufficient for this type of analysis. The
      strengths and limitations of the method are discussed. Inhibition constants for
      filamin and spectrin determined by this method are 125 nM and 13 nM respectively.

PMID- 9928945
TI  - Stimulation of the catalytic activity of poly(ADP-ribosyl) transferase by
      transcription factor Yin Yang 1.
AB  - The transcriptional regulator Yin Yang 1 (YY1) has previously been demonstrated
      to physically interact with poly(ADP-ribosyl) transferase (ADPRT). This nuclear
      enzyme catalyzes the synthesis of ADP-ribose polymers and their attachment to
      target proteins. It is reported here that YY1 associates preferably with the
      extensively auto(ADP-ribosyl)ated form of ADPRT, but not with deproteinized ADP
      ribose polymers. In the presence of YY1 the catalytic rate of ADPRT is enhanced
      about 10-fold. This stimulation is in part due to modification of YY1, thus
      serving as a substrate of the reaction. In addition, automodification of ADPRT is
      also substantially increased. The activation by YY1 is most pronounced at low
      concentrations of ADPRT suggesting that the presence of YY1 may either facilitate
      the formation of catalytically active dimers of ADPRT or lead to the occurrence
      of active heterooligomers. The potential significance of these observations was
      verified by analyzing the activity of ADPRT in HeLa nuclear extracts. The
      endogenous enzyme exhibited an about 10-fold higher activity as compared to the
      isolated recombinant protein. It is likely that the heat-stable transcription
      factor YY1 contributed to the increased activity of ADPRT detected in the nuclear
      extracts, because heated extracts had a similar stimulatory effect on isolated
      ADPRT as isolated YY1 used at comparable concentrations. It is concluded that YY1
      may be an important regulator of ADPRT and, therefore, could support the function
      of ADPRT to facilitate DNA repair.

PMID- 9928946
TI  - Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells
      transfected with Edg-3, a putative lipid receptor.
AB  - Sphingosine 1-phosphate (S1P) induces phospholipase C (PLC) activation and Ca2+
      mobilization in many types of cells. We examined the possible involvement of Edg
      3, one of the putative S1P receptors, in the phospholipase C (PLC)-Ca2+ system.
      S1P increased the cytoplasmic free Ca2+ concentration without detectable inositol
      phosphate production in vector-transfected CHO cells. In the Edg-3-transfected
      cells, however, the S1P-induced Ca2+ response was clearly enhanced, which was
      associated with a significant production of inositol phosphate. These S1P-induced
      responses in the Edg-3-transfected cells were inhibited by U73122, a potent PLC
      inhibitor. We conclude that Edg-3 may be one of the S1P receptors participating
      in the activation of the PLC-Ca2+ system.

PMID- 9928947
TI  - Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in
      its insensitivity to calpain.
AB  - The ERM proteins, ezrin, radixin and moesin, provide regulated linkage of the
      cytoskeleton with the plasma membrane, particularly in cell surface projections.
      Ezrin and moesin were found co-expressed, and radixin was not detected, in human
      blood lymphocytes, monocytes and neutrophils. Moesin is the quantitatively
      dominant ERM protein in these cells and the only one in platelets. Because Ca
      signaling pathways involving calpain cleavages are important in blood cells, we
      examined ERM protein sensitivity to this protease. A striking difference was
      discovered: sensitivity of ezrin and resistance of moesin (and radixin) to
      calpain. In intact stimulated lymphocytes, ezrin was cleaved, while moesin was
      not, strongly suggesting that differential sensitivity to calpain contributes to
      specialized functions of these proteins.

PMID- 9928948
TI  - Effects of nitric oxide on the eosinophil survival in vitro. A role for nitrosyl
      heme.
AB  - In a previous paper we showed that the nitric oxide (NO) donors azide and
      hydroxylamine inhibited eosinophil apoptosis. Azide and hydroxylamine generate a
      nitrosyl-heme complex - due to endogenous catalase activity - which activates
      soluble guanylate cyclase. In contrast, in the present paper, we show that NO
      donors (SNAP, SIN-1, S-nitroso-L-cysteine, NOC-18) which spontaneously release NO
      in physiological solutions did not support the survival of eosinophils and
      induced apoptosis or necrosis. However, the addition of hematin (the ferric form
      of heme) together with low doses of NO (SNAP 10 microM) promoted eosinophil
      survival. In conclusion, we propose that NO and heme (e.g. from heme-containing
      enzymes such as peroxidase or catalase), both released in inflammation sites,
      could form nitrosyl-heme and thus promote eosinophilic inflammation.

PMID- 9928950
TI  - Prorenin processing by cathepsin B in vitro and in transfected cells.
AB  - Renin, which catalyzes the initial proteolytic cleavage reaction in the
      production of angiotensins, is first synthesized as a zymogen, prorenin, and
      requires the proteolytic removal of an amino-terminal prosegment for activation
      in vivo. The lysosomal hydrolase cathepsin B has been proposed as a prorenin
      processing enzyme based on reports of its co-localization with renin in the
      secretory granules of certain tissues and its ability to activate prorenin in
      vitro. In the current study, scanning mutagenesis was used to identify the amino
      acids which determine the site selectivity of prorenin cleavage by human
      cathepsin B in vitro. Co-expression assays in AtT-20 cells were also used to test
      for the ability of cathepsin B to cleave human prorenin within cells. Our results
      suggest that a basic lysine residue at the -2 position from the cleavage site is
      required for cathepsin B cleavage of prorenin in vitro and that the structure of
      prorenin itself may account for the selection of the proper cleavage site. In
      addition, although cathepsin B appears to be correctly sorted to lysosomes, the
      enzyme exhibits prorenin processing activity in transfected AtT-20 cells, raising
      the question of the cellular localization in which the processing event occurs.

PMID- 9928949
TI  - C-terminal domains of human translation termination factors eRF1 and eRF3 mediate
      their in vivo interaction.
AB  - At the termination step of protein synthesis, hydrolysis of the peptidyl-tRNA is
      jointly catalysed at the ribosome by the termination codon and the polypeptide
      release factor (eRF1 in eukaryotes). eRF1 forms in vivo and in vitro a stable
      complex with release factor eRF3, an eRF1-dependent and ribosome-dependent
      GTPase. The role of the eRF1-eRF3 complex in translation remains unclear. We have
      undertaken a systematic analysis of the interactions between the human eRF1 and
      eRF3 employing a yeast two-hybrid assay. We show that the N-terminal parts of
      eRF1 (positions 1-280) and of eRF3 (positions 1477) are either not involved or
      non-essential for binding. Two regions in each factor are critical for mutual
      binding: positions 478-530 and 628-637 of eRF3 and positions 281-305 and 411-415
      of eRF1. The GTP binding domain of eRF3 is not involved in complex formation with
      eRF1. The GILRY pentamer (positions 411-415) conserved in eukaryotes and
      archaebacteria is critical for eRF1's ability to stimulate eRF3 GTPase. The human
      eRF1 lacking 22 C-terminal amino acids remains active as a release factor and
      promotes an eRF3 GTPase activity whereas C-terminally truncated eRF3 is inactive
      as a GTPase.

PMID- 9928951
TI  - Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an
      insulinoma cell line (INS-1).
AB  - Primer extension analysis and RNase protection assays revealed the identity of
      glucose 6-phosphatase gene transcripts in both the insulinoma cell line INS-1 and
      hepatic cells. In transient transfection assays of INS-1 cells, using constructs
      between the human glucose 6-phosphatase gene promoter and a luciferase reporter
      gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP.
      Furthermore, the promoter was regulated by the glucose concentration in the
      medium. This effect was dependent on glucose metabolism. The data indicated that
      glucose 6-phosphatase gene transcription is regulated in a similar way in the
      insulinoma cell line and in liver.

PMID- 9928952
TI  - Purification and characterization of a major 40 kDa outer membrane protein of
      Acinetobacter baumannii.
AB  - Acinetobacter baumannii, an opportunistic pathogen, is well known to cause a wide
      spectrum of nosocomial infections particularly in intensive care units. The major
      outer membrane (OM) protein, OmpAb, of 40 kDa from A. baumannii has been
      identified and purified to homogeneity from cultures grown at 30 degrees C and
      100 mM NaCl. The synthesis of OM proteins of A. baumannii is thermoregulated and
      osmoregulated. The pore forming ability of the purified OmpAb and the diffusion
      of uncharged solutes in proteoliposomes has been demonstrated by following the
      liposomal swelling assay. The trimeric OmpAb is characterized as a porin with a
      pore size of 1.3 nm and is found to be similar to the OmpF of Escherichia coli
      and can possibly be classified as a general diffusion pore. It appears that OmpAb
      plays an important role in the diffusion properties of the outer membrane of A.
      baumannii.

PMID- 9928953
TI  - Uptake by rat liver and intracellular fate of plasmid DNA complexed with poly-L
      lysine or poly-D-lysine.
AB  - Efficiency of transfection is probably dependent on the rate of intracellular
      degradation of plasmid DNA. When a non-viral vector is used, it is not known to
      what extent the plasmid DNA catabolism is subordinated to the catabolism of the
      vector. In the work reported here, the problem was approached by following the
      intracellular fate in rat liver, of plasmid [35S]DNA complexed with a cationic
      peptide poly-L-lysine that can be hydrolyzed by cellular peptidases or with its
      stereoisomer, poly-D-lysine, that cannot be split by these enzymes. Complexes of
      DNA with poly-L-lysine and poly-D-lysine are taken up to the same extent by the
      liver, mainly by Kupffer cells, but the intracellular degradation of nucleic acid
      molecules is markedly quicker when poly-L-lysine is injected. The association of
      DNA with the polycations inhibits DNA hydrolysis in vitro by purified lysosomes
      but similarly for poly-L-lysine and poly-D-lysine. The intracellular journey
      followed by [35S]DNA complexed with poly-L- or poly-D-lysine was investigated
      using differential and isopycnic centrifugation. Results indicate that [35S]DNA
      is transferred more slowly to lysosomes, the main site of intracellular
      degradation of endocytosed macromolecules, when it is given as a complex with
      poly-D-lysine than with poly-L-lysine. They suggest that the digestion of the
      vector in a prelysosomal compartment is required to allow endocytosed plasmid DNA
      to rapidly reach lysosomes. Such a phenomenon could explain why injected plasmid
      DNA is more stable in vivo when it is associated with poly-D-lysine.

PMID- 9928954
TI  - Phosphoinositide 3-kinase and integrin signalling are involved in activation of
      Bruton tyrosine kinase in thrombin-stimulated platelets.
AB  - Bruton tyrosine kinase (Btk) plays a crucial role in the differentiation of B
      lymphocytes and belongs to the group of Tec kinases, which are characterised by
      the presence of a pleckstrin homology domain. Here we show that Btk is activated
      and undergoes tyrosine phosphorylation upon challenge of platelet thrombin
      receptor, these responses requiring engagement of alphaIIb/beta3 integrin and
      phosphoinositide 3-kinase activity. These data unravel a novel signalling pathway
      involving Btk downstream of an adhesive receptor via a complex regulation
      implicating the products of phosphoinositide 3-kinase, which might act to anchor
      Btk at the membrane.

PMID- 9928955
TI  - Interaction between the fission yeast nim1/cdr1 protein kinase and a dynamin
      related protein.
AB  - The nim1/cdr1 protein kinase is required for an efficient adaptation of cell
      cycle parameters to changes in nutritional conditions. We have isolated msp1, a
      new fission yeast member of the dynamin-related large GTPase family, in a two
      hybrid screen designed to identify proteins interacting with the nim1 kinase.
      Msp1 has been shown to be essential for the maintenance of mtDNA and hence for
      the inheritance of functional mitochondria. We present evidence indicating that
      niml and mspl proteins physically interact both in vitro and in vivo in fission
      yeast. These interactions occur through the amino-terminal catalytic domain of
      nim1 and the carboxy-terminal putative regulatory domain of mspl. These results
      provide new evidence for the existence of a connection between mitochondrial
      function and the cell cycle machinery.

PMID- 9928956
TI  - AT2 receptor stimulation induces generation of ceramides in PC12W cells.
AB  - The angiotensin AT2 receptor has been implicated in both regeneration and
      apoptosis. To further investigate the molecular mechanisms leading to AT2
      receptor-induced programmed cell death in PC12W cells we studied the effects of
      angiotensin II (ANG II) on ceramide levels by HPTLC analysis. We could
      demonstrate that ANG II time- (1-10 h) and dose-dependently (10(-8)-5 X 10(-6) M)
      increased ceramide levels by maximally 175% but did not affect sphingomyelin
      degradation. The ANG 11 effects were mediated by AT2 receptors since they were
      completely abolished by co-incubation with the AT2 receptor antagonist, PD123177
      (10(-5) M), but not by the AT1 receptor antagonist, losartan (10(-5) M). These
      data suggest a novel signal transduction pathway to the AT2 receptor leading to
      apoptosis in neuronal cells.

PMID- 9928957
TI  - Kinetic and spectroscopic characterization of an intermediate peroxynitrite
      complex in the nitrogen monoxide induced oxidation of oxyhemoglobin.
AB  - Stopped-flow spectroscopy studies of the nitrogen monoxide mediated oxidation of
      oxyhemoglobin in the pH range 5-10.5 show that an intermediate can be
      characterized at alkaline pH. The rate of decay of this species to methemoglobin
      increases significantly with decreasing pH such that it does not accumulate in
      quantities large enough to be observed under neutral or acidic conditions.
      Kinetic and spectroscopic properties of this intermediate support its assignment
      as a methemoglobin peroxynitrite complex.

PMID- 9928958
TI  - The mentor relationship.

PMID- 9928959
TI  - What are we teaching about lifting and transferring patients?
AB  - Lifting patients under the axilla has been found to be physically stressful for
      nurses and uncomfortable for patients. The goals of this study were to find out:
      how often educators teach this method and observe it in the clinical field; which
      assistive devices are used in teaching; and what authors of textbooks teach about
      the under-axilla method. A questionnaire was sent to 546 baccalaureate (BS) and
      associate (AD) degree programs; 358 educators responded and 337 responses were
      analyzed. Eighty-three percent of the educators teach the under-axilla method for
      in- and out-of-bed transfers; 94% observe it used in the clinical field. For
      lifting up in bed, 56% teach the under-axilla method; 86% observe it in the
      clinical field. When assistive devices are included in teaching, the hydraulic
      lift and gait belt are taught most often; less stressful and more comfortable
      devices are not taught or observed by most respondents. None of the authors of
      the 3 most frequently used textbooks describe the use of the under-axilla method;
      authors of 2 textbooks state patients should not have pressure placed on the
      axilla area.

PMID- 9928960
TI  - Behavior problems among young children in low-income urban day care centers.
AB  - The purposes of this study were to describe: (a) the frequency and correlates of
      behavior problems among a sample of 2- and 3-year-old children from low-income
      families as seen by their parents and day care teachers, (b) the degree to which
      parents and teachers agree about the children's behavior problems in their
      respective contexts, and (c) family characteristics that distinguish toddlers
      with behavior problems both at home and at day care from the rest of the sample.
      Parents of 133 toddlers from 10 Chicago day care centers completed measures of
      child behavior problems, child behavioral intensity, parenting self-efficacy,
      discipline strategies, and stress. Children's day care teachers also completed a
      measure of child behavior problems. Parent-reported behavior problems were
      associated with higher child behavioral intensity, greater parent stress, lower
      self-efficacy, and discipline strategies characterized by irritability, coercion,
      and inconsistency. Parent and teacher ratings on child behavior were correlated
      for boys' behavior problems only. Parents reported more child behavior problems
      than teachers. Approximately 8% of the children were rated as having behavior
      problems at home and at day care. Although most of the children are functioning
      well, many of these parents and toddlers are engaged in highly stressful and
      coercive relationships.

PMID- 9928961
TI  - Development and testing of the Resistiveness to Care Scale.
AB  - A conceptual model and objective scale for measuring resistiveness to care in
      individuals with advanced dementia of the Alzheimer type (DAT) were empirically
      generated from the perspective of nursing staff caregivers and through
      observation of residents with DAT. The resistiveness to care scale (RTC-DAT) was
      judged to have content validity and reduced to 13 items. Quantifiable scoring
      procedures and methods for rating videotapes and conducting clinical observations
      were developed. The RTC-DAT was tested with 68 subjects at three sites. The RTC
      has a range of 0-156. Initial testing provided reliability estimates of .82-.87
      for internal consistency and good to excellent kappas. Criterion-related validity
      with observed discomfort and construct validity by factor analysis support the
      RTC-DAT. Measurement issues and recommendations for use in research are
      discussed.

PMID- 9928962
TI  - Decision-making preference and opportunity in VA ambulatory care patients:
      association with patient satisfaction.
AB  - Using data from the Veterans Health Study, associations were examined for
      decision-making preference, decision-making opportunity, and satisfaction with
      medical care among a sample of 266 men who use Department of Veterans Affairs
      (VA) ambulatory health care services. Results indicated that veterans with a high
      preference for involvement in decision-making and low provider-offered decision
      making opportunities had significantly lower satisfaction with medical care
      compared to veterans with either low preference for decision-making involvement
      with high or low opportunity, or those with a high decision-making preference and
      high decision-making opportunity. The findings suggest that health care providers
      may increase patient satisfaction with medical care by providing opportunities
      for decision-making to patients who prefer involvement in their health care
      decision-making. Provider strategies for increasing patient decision-making
      involvement are discussed.

PMID- 9928963
TI  - Women's responses to battering: a test of the model.
AB  - A volunteer community sample of 141 well-educated, economically heterogeneous,
      primarily African American (80%), urban battered women was used to test a model
      of women's responses to battering. The model, based on Orem's theory, was
      developed previously with an independent sample. The major independent variables
      were physical and nonphysical abuse, and self-care agency. The outcomes were
      physical and emotional health. Using structural equation modeling techniques,
      there was sufficient support for the model structure to conclude preliminary
      support for the overall model. There was both a direct effect of abuse on health,
      and an indirect effect mediated through self-care agency as a protective factor.

PMID- 9928964
TI  - Testing an intervention to prevent further abuse to pregnant women.
AB  - Although violence against women is recognized as a major public health problem,
      few interventions have been developed to reduce abuse. In this study, 132
      pregnant women received three counseling sessions that were designed to reduce
      further abuse. A comparison group of 67 abused women were offered wallet-sized
      cards listing community resources for abuse. Women in both groups were followed
      at 6 months and 12 months post-delivery. Using repeated measures MANCOVA with
      entry scores as a covariate, we found significantly less violence reported by
      women in the intervention group than by women in the comparison group.

PMID- 9928965
TI  - Functional status from the patient's perspective: the challenge of preserving
      personal integrity.
AB  - The purpose of this naturalistic, qualitative study was to describe the meaning
      of functional performance from the perspective of patients themselves. Twelve men
      and women with moderate to severe chronic obstructive pulmonary disease (COPD)
      participated in unstructured, tape-recorded interviews. The essential structure
      of the experience of finding purpose and meaning through activity was derived
      through an adaptation of Colaizzi's phenomenological method and the consensus
      dialogue approach to concept clarification. Results suggest people who are ill
      face an ongoing challenge of preserving their personal integrity, defined as a
      satisfying sense of wholeness, as they encounter a variety of physical changes
      that can interfere with day-to-day activity. Qualities most salient to integrity
      are a sense of effectiveness, or "being able," and of connectedness, or "being
      with." Identifying personal integrity as a motivating and explanatory factor in
      day-to-day activity performance may be an important consideration in designing
      effective intervention programs to improve capacity, strengthen performance, and
      enhance quality of life.

PMID- 9928966
TI  - Time and qualitative research.
AB  - Qualitative researchers may bear a special obligation in relation to time, as the
      context they hope to preserve for the phenomena they study is, in large part,
      temporal. Temporal concerns are integral to qualitative research, whether the
      focus is on disciplines in which largely qualitative methods are used, paradigms
      of inquiry that are primarily associated with qualitative methods, or on
      qualitative methods themselves. Temporal factors play a critical role in
      purposive sampling, the content and structure of data collection and analysis
      techniques, and in the re-presentation of data in the qualitative research
      report. Qualitative research designs may be oriented to synchronic and/or
      diachronic analyses. The Trajectory Model is a useful framework for sampling,
      data collection, and analysis. The Storyline Graph is a tool especially useful in
      narrative research.

PMID- 9928967
TI  - Rapid-sequence intubation: a safe but ill-defined procedure.

PMID- 9928968
TI  - The problem of ambulance misuse: whose problem is it, anyway?

PMID- 9928969
TI  - Appropriate emergency medical services transport.

PMID- 9928970
TI  - Multivariate predictive models for group A beta-hemolytic streptococcal
      pharyngitis in children.
AB  - OBJECTIVES: To create predictive models for the clinical diagnosis of group A
      beta-hemolytic streptococcal (GABHS) pharyngitis in children. METHODS: Patients
      aged 6 months to 18 years presenting to a pediatric ED with suspected GABHS
      pharyngitis were prospectively enrolled in the study. Clinicians recorded
      pertinent clinical information using a standardized form and obtained a throat
      swab to culture GABHS using a reference standard method. Twelve demographic and
      clinical features of patients with positive throat cultures were compared with
      the features of patients with negative throat cultures. Significantly different
      features were entered in a stepwise logistic regression analysis to create
      predictive models for the diagnosis. RESULTS: Eighty-five patients (29%) were
      culture-positive and 212 (71%) were culture-negative for GABHS. Respective mean
      ages were 6.2 years and 6.1 years in the two groups. Univariate chi-square
      analysis of the 12 features identified six variables that were significantly
      associated with GABHS. All significant features were initially included in a
      stepwise logistic regression analysis. In model I, four independent variables
      were identified: moderate to severe presentation of tonsillar swelling, moderate
      to severe tenderness and enlargement of cervical lymph nodes, the presence of
      scarlatiniform rash, and the absence of moderate to severe coryza, yielding a 95%
      probability for GABHS. Excluding the rare scarlatiniform rash, the remaining
      variables were used in the second regression analysis. In model II, three
      independent variables were identified: moderate to severe tonsillar swelling,
      moderate to severe tenderness and enlargement of cervical lymph nodes, and
      absence of moderate to severe coryza, yielding a probability of 65% for the
      diagnosis. A probability of <15% was observed in the absence of scarlatiniform
      rash, the absence of moderate to severe tenderness and enlargement of cervical
      lymph nodes, and the presence of moderate to severe coryza. CONCLUSIONS: In
      children with moderate to severe presentation of tonsillar swelling, tenderness
      and enlargement of cervical lymph nodes, and the absence of coryza, the
      probability of a positive throat culture is >65%. Conversely, in the absence of a
      moderate to severe presentation of tonsillar swelling, enlargement of cervical
      nodes, and the presence of coryza, the probability of a positive throat culture
      is <15%. If prospectively validated, these models could be integrated into a
      consistent treat, test, and no treatment/no testing approach to the clinical
      management of childhood pharyngitis.

PMID- 9928971
TI  - Inappropriate use of emergency medical services transport: comparison of provider
      and patient perspectives.
AB  - OBJECTIVES: To determine the extent of inappropriate ambulance use from the
      perspectives of both emergency medical services (EMS) providers and patients
      utilizing EMS transport, assess level of agreement, and identify variables
      associated with inappropriate ambulance use. METHODS: A prospective cross
      sectional study was done of a consecutive sample of patients arriving by
      ambulance during the month of February 1997 at an urban university hospital ED.
      EMS providers and patients completed a survey with questions regarding their
      perceptions of whether the need for ambulance transport was an emergency or a
      nonemergency. Patient demographic information and availability of alternate means
      of transportation to the hospital were also evaluated. RESULTS: Eight hundred
      eighty-seven patients were included in the study. EMS providers thought that 501
      patient transports were appropriate and represented true emergencies, whereas 689
      patients believed their medical problems were true emergencies. A significant
      number of patients (n=415, 47%) had access to alternative transportation to the
      hospital. Blunt traumatic injury and altered mental status were the most common
      reasons for EMS transport. Patient characteristics significantly associated with
      EMS provider perception of a true emergency were male gender, age >51 years,
      higher education, chest pain/cardiac complaints, shortness of breath/respiratory
      complaints, and Medicare insurance. Characteristics significantly associated with
      patients who perceived themselves to have true emergencies were black ethnicity,
      higher education, shortness of breath/respiratory complaints, and Medicare
      insurance. There was 75% agreement between EMS providers and patients on
      appropriateness of ambulance transport (kappa=0.84). CONCLUSION: Inappropriate
      ambulance use is a significant problem from both EMS provider and patient
      perspectives. Certain patient characteristics are associated with a higher
      probability of appropriate and inappropriate uses of EMS transport. A large
      number of patients transported by ambulance have alternative means of
      transportation but elect not to use them.

PMID- 9928972
TI  - What is the optimal dose of intramuscular ketamine for pediatric sedation?
AB  - OBJECTIVE: The optimal dose of i.m. ketamine for ED procedural sedation in
      children is not known. The authors wished to quantify the dose-response of
      ketamine with respect to sedation adequacy, time to discharge, and adverse
      effects in order to identify an optimal dose. METHODS: The study was a
      consecutive case series of 1,022 children < or = 15 years of age given i.m.
      ketamine in the EDs of a university medical center and an affiliated county
      hospital over a nine-year period. Adequacy of sedation, time to discharge, and
      adverse effects were compared with dose administered. RESULTS: Doses in the
      sample averaged 3.96+/-0.69 mg/kg, with a range of 0.48 to 9.09 mg/kg. Children
      judged to be adequately sedated received higher doses compared with those
      inadequately sedated (3.94+/-0.44 mg/kg vs 3.77+/-0.49 mg/kg, p=0.041), and a
      nonsignificant trend was noted toward uniformly adequate sedation with increasing
      dose (< or =91% at <4.00 mg/kg, 93% at 4.00-4.49 mg/kg, and 100% at > or = 4.50
      mg/kg). No significant difference or trend in time to discharge or adverse
      effects was noted between the children receiving <4.00 mg/kg and those receiving
      > or = 4.00 mg/kg of ketamine, and the study had power (alpha=0.05, beta=0.20) to
      detect a 9-minute difference in times to discharge, a 3.3% difference in rates of
      airway complications, a 5.6% difference in rates of emesis, and a 12.3%
      difference in rates of recovery agitation. CONCLUSION: Ketamine doses of 4 to 5
      mg/kg i.m. produced adequate sedation in 93%-100% of children, suggesting that
      this dosing range may be optimal for ED procedural sedation. No difference in
      time to discharge or adverse effects was observed for lower or higher doses.

PMID- 9928973
TI  - Osmol gaps in the pediatric population.
AB  - OBJECTIVE: To define the osmol gap (OG) range in pediatric ED (PED) patients.
      METHODS: This was a blinded, observational patient series involving an urban PED
      with an annual census of 35,000. All patients presenting to the Hasbro Children's
      Hospital Emergency Department who required electrolyte determination during their
      evaluations were enrolled into the study. Exclusionary criteria included the
      presence of urinary ketones, alcohol ingestion within the preceding 24 hours, or
      illnesses that are known to change serum osmolarity. Electrolytes, BUN, glucose,
      and freezing point depression osmolality were measured on a single serum
      specimen. Additional laboratory information included ethanol and anion gap. The
      OG was determined using each of three equations previously described in the
      literature (see Results). The best coefficients for sodium, BUN, and glucose were
      determined by multiple linear regression. RESULTS: 192 children (90 girls, 102
      boys) with a median age of 6.6 years (mean: 7.3 years; range: 7 days to 17.9
      years) made up the study population. The mean measured osmolality (+/-SD) for the
      entire sample was 284.2+/-6.9 mOsm/dL with a range of 265-311 mOsm/dL. Mean osmol
      gaps with standard deviations varied with the equation used for calculation.
      CONCLUSION: Regardless of the equation used, the range of "normal" osmol gaps in
      the pediatric population is approximately 22 mOsm.

PMID- 9928974
TI  - Rapid-sequence intubation at an emergency medicine residency: success rate and
      adverse events during a two-year period.
AB  - OBJECTIVES: Rapid-sequence intubation (RSI) is an active airway intervention used
      frequently in emergency medicine (EM). The authors hypothesized that RSI can be
      performed safely in the setting of an EM training program at a tertiary care
      center. METHODS: Observational study of RSI at an urban ED/Level 1 trauma center
      with annual census of 100,000 patients. Consecutive patients who underwent RSI
      during a two-year period were studied. Data included age, gender, type of patient
      (medical/trauma), indication for intubation, number of intubation attempts
      (laryngoscope passes), training level of operator, and major immediate adverse
      events (clinical deterioration within 10 minutes of RSI). RESULTS: RSI was used
      in 417 of 596 (70%) critically ill patients requiring emergent intubation. The
      patient demographic distribution was the following: adults 89.7%, male 58%, and
      trauma 44%. Primary indications for intubation among RSI patients were as
      follows: mechanical ventilation 57.4%, airway protection 41.3%, and cardiac
      arrest 1.3%. Distribution of intubations by level of EM training was PGY1, 5%;
      PGY2, 52%; PGY3, 40%; and attendings, 3%. Intubations were successfully completed
      within two attempts in 97% of the patients. Major immediate adverse events were
      encountered in six patients (1.4%) (hypotention=2, hypoxemia=1, dysrhythmia=3).
      There was no death attributable to RSI. The rate of intubations requiring two or
      fewer attempts and without major immediate adverse events was 96%. Three patients
      required cricothyrotomy. CONCLUSION: In the setting of an EM residency at a
      tertiary care ED, RSI can be performed successfully with few major immediate
      adverse events.

PMID- 9928976
TI  - A code of conduct for academic emergency medicine. SAEM Ethics Committee. Society
      for Academic Emergency Medicine.

PMID- 9928975
TI  - Interobserver variability among faculty in evaluations of residents' clinical
      skills.
AB  - OBJECTIVE: To describe interobserver variability among emergency medicine (EM)
      faculty when using global assessment (GA) rating scales and performance-based
      criterion (PBC) checklists to evaluate EM residents' clinical skills during
      standardized patient (SP) encounters. METHODS: Six EM residents were videotaped
      during encounters with SPs and subsequently evaluated by 38 EM faculty at four EM
      residency sites. There were two encounters in which a single SP presented with
      headache, two in which a second SP presented with chest pain, and two in which a
      third SP presented with abdominal pain, resulting in two parallel sets of three.
      Faculty used GA rating scales to evaluate history taking, physical examination,
      and interpersonal skills for the initial set of three cases. Each encounter in
      the second set was evaluated with complaint-specific PBC checklists developed by
      SAEM's National Consensus Group on Clinical Skills Task Force. RESULTS: Standard
      deviations, computed for each score distribution, were generally similar across
      evaluation methods. None of the distributions deviated significantly from that of
      a Gaussian distribution, as indicated by the Kolmogorov-Smirnov goodness-of-fit
      test. On PBC checklists, 80% agreement among faculty observers was found for 74%
      of chest pain, 45% of headache, and 30% of abdominal pain items. CONCLUSIONS:
      When EM faculty evaluate clinical performance of EM residents during videotaped
      SP encounters, interobserver variabilities are similar, whether a PBC checklist
      or a GA rating scale is used.

PMID- 9928977
TI  - EMS systems: foundations for the future.
AB  - Emergency medical services (EMS) occupy a unique position in the continuum of
      emergency health care delivery. The role of EMS personnel is expanding beyond
      their traditional identity as out-of-hospital care providers, to include
      participation and active leadership in EMS administration, education, and
      research. With these roles come new challenges, as well as new responsibilities.
      This paper was developed by the SAEM EMS Task Force and provides a discussion of
      these new concepts as well as recommendations for the specialty of emergency
      medicine to foster the continued development of all of the potentials of EMS.

PMID- 9928978
TI  - Statistical methodology: VIII. Using confirmatory factor analysis (CFA) in
      emergency medicine research.
AB  - How many underlying characteristics (or factors) does a set of survey questions
      measure? When subjects answer a set of self-report questions, is it more
      appropriate to analyze the questions individually, to pool responses to all of
      the questions to form one global score, or to combine subsets of related
      questions to define multiple underlying factors? Factor analysis is the
      statistical method of choice for answering such questions. When researchers have
      no idea beforehand about what factors may underlie a set of questions, they use
      exploratory factor analysis to infer the best explanatory model from observed
      data "after the fact." If, on the other hand, researchers have a hypothesis
      beforehand about the underlying factors, then they can use confirmatory factor
      analysis (CFA) to evaluate how well this model explains the observed data and to
      compare the model's goodness-of-fit with that of other competing models. This
      article describes the basic rules and building blocks of CFA: what it is, how it
      works, and how researchers can use it. The authors begin by placing CFA in the
      context of a common research application-namely, assessing quality of medical
      outcome using a patient satisfaction survey. They then explain, within this
      research context, how CFA is used to evaluate the explanatory power of a factor
      model and to decide which model or models best represent the data. The
      information that must be specified in the analysis to estimate a CFA model is
      highlighted, and the statistical assumptions and limitations of this analysis are
      noted. Analyzing the responses of 1,614 emergency medical patients to a commonly
      used "patient satisfaction" questionnaire, the authors demonstrate how to: 1)
      compare competing factor-models to find the best-fitting model; 2) modify models
      to improve their goodness-of-fit; 3) test hypotheses about relationships among
      the underlying factors; 4) examine mean differences in "factor scores"; and 5)
      refine an existing instrument into a more streamlined form that has fewer
      questions and better conceptual and statistical precision than the original
      instrument. Finally, the role of CFA in developing new instruments is discussed.

PMID- 9928979
TI  - Research fundamentals: IV. Choosing a research design.
AB  - Once a research question or hypothesis has been derived, the investigator must
      determine which research methodology can best answer his or her question.
      Prospective, randomized, controlled trials are often considered the sine qua non
      of research design. However, this study design is not always feasible, and often
      an alternate design will adequately answer the question at significantly less
      cost. All research designs have potential advantages and limitations. The
      decision of which study design to use is often a compromise between science and
      resources. This article was prepared by members of the SAEM Research Committee to
      describe the fundamental research concepts of research design. This paper defines
      different research methodologies and discusses their different uses, strengths,
      and weaknesses. It also describes the process of randomization and blinding.
      Finally, the concept of bias and its remedies is delineated.

PMID- 9928980
TI  - Research fundamentals: V. The use of laboratory animal models in research.
AB  - Animal research has provided important information about many aspects of the
      pathophysiology of human disease. Well-performed animal studies can determine the
      potential benefit of many proposed therapeutic interventions, and experimental
      results from animal studies have served as the basis for many landmark clinical
      trials. Many animal research models are described in the research literature, and
      choosing the appropriate model to answer a research question can be a daunting
      task. Even more challenging is developing a new model when none of the existing
      systems are relevant to the proposed question. This article was prepared by
      members of the SAEM Research Committee to provide an overview of animal modeling.
      Important considerations in choosing, applying, and developing animal research
      models are outlined. Practical discussions of potential problems with animal
      models are also provided.

PMID- 9928981
TI  - Acute gastric volvulus: a case report.

PMID- 9928982
TI  - Emergency physician-performed ultrasonography-guided hip arthrocentesis.

PMID- 9928983
TI  - Ketamine sedation in mentally disabled adults.

PMID- 9928984
TI  - Refusal of care.

PMID- 9928985
TI  - End-tidal carbon dioxide monitoring in cardiac arrest.

PMID- 9928986
TI  - RGD-dependent growth of maize calluses and immunodetection of an integrin-like
      protein.
AB  - When maize calluses are grown in the presence of the RGD peptide, important
      morphological changes are observed indicating the presence of a likely RGD
      binding receptor. Polyclonal antibodies generated against the human beta1
      integrin subunit, the platelet integrin alphaIIbeta3 (P23) and antibodies
      specific for either the beta3 platelet chain or the alphaIIb polypeptide cross
      react with glycoproteins in Western blot analyses. Immunoprecipitation assays
      indicate that this maize integrin-like protein shares structural similarities
      with the animal alphaIIbeta3 complex. We also show that AcAt2, a polyclonal
      antibody raised against Arabidopsis proteins purified on an RGD column, interacts
      with a maize protein.

PMID- 9928987
TI  - Redox agents regulate ion channel activity in vacuoles from higher plant cells.
AB  - The ability of redox agents to modulate certain characteristics of voltage- and
      calcium-activated channels has been recently investigated in a variety of animal
      cells. We report here the first evidence that redox agents regulate the
      activation of ion channels in the tonoplast of higher plants. Using the patch
      clamp technique, we have demonstrated that, in tonoplasts from the leaves of the
      marine seagrass Posidonia oceanica and the root of the sugar beet, a variety of
      sulphydryl reducing agents, added at the cytoplasmic side of the vacuole,
      reversibly favoured the activation of the voltage-dependent slow vacuolar (SV)
      channel. Antioxidants, like dithiothreitol (DTT) and the reduced form of
      glutathione, gave a reversible increase of the voltage-activated current and
      faster kinetics of channel activation. Other reducing agents, such as ascorbic
      acid, also increased the SV currents, although to a lesser extent in comparison
      with DTT and glutathione, while the oxidising agent chloramine-T irreversibly
      abolished the activity of the channel. Single channel experiments demonstrated
      that DTT reversibly increased the open probability of the channel, leaving the
      conductance unaltered. The regulation of channel activation by glutathione may
      correlate ion transport with other crucial mechanisms that in plants control
      turgor regulation, response to oxidative stresses, detoxification and resistance
      to heavy metals.

PMID- 9928988
TI  - Identification and characterization of a novel splice variant of MuSK.
AB  - MuSK is a receptor tyrosine kinase that initiates the formation of neuromuscular
      junctions in response to agrin. Little is known about the ligand-induced
      activation and kinase-dependent signalling that leads to the clustering of
      acetylcholine receptors. The ectodomain of these molecule is composed of four Ig
      like domains. We describe here the isolation of a novel MuSK splice variant that
      lacks the third Ig-like domain in its ectodomain. The corresponding RNA is the
      result of alternative splicing which eliminates two exons. There is 10 times less
      mRNA for this shorter form than for the long form of MuSK and both forms are
      regulated coordinately. They decrease strongly after birth and are elevated in
      denervated muscle. Gene transfer by muscle injection of MuSK DNA into individual
      muscle fibers demonstrates that kinase-induced acetylcholine receptor clustering
      caused by overexpression of the two kinases does not depend on the presence of
      the third Ig-like domain.

PMID- 9928989
TI  - Solution structure of the Eps15 homology domain of a human POB1 (partner of
      RalBP1).
AB  - The solution structure of the Eps15 homology (EH) domain of a human POB1 (partner
      of RaIBP1) has been determined by uniform 13C/15N labeling and heteronuclear
      multidimensional nuclear magnetic resonance spectroscopy. The POB1 EH domain
      consists of two EF-hand structures, and the second one binds a calcium ion. In
      the calcium-bound state, the orientation of the fourth alpha-helix relative to
      the other helices of the POB1 EH domain is slightly different from that of
      calbindin, and much more different from those of calmodulin and troponin C, on
      the basis of their atomic coordinates.

PMID- 9928990
TI  - Calcium-dependent interaction of annexin I with annexin II and mapping of the
      interaction sites.
AB  - Annexins are multifunctional intracellular proteins with Ca2+- and phospholipid
      binding properties. Their structures consist of four conserved repeat domains
      that form the core and a diverse N-terminal tail, from which their functional
      differences may arise. We searched for cellular proteins that interact with the N
      terminal tail plus domain I of annexin I (ANX1) by using the yeast two-hybrid
      method. Screening of a HeLa cell cDNA library yielded annexin II (ANX2) cDNA. The
      interaction between ANX1 and ANX2 also occurred in vitro in a Ca2+-dependent
      manner. Mapping of the interaction sites revealed that interaction between domain
      I of ANX1 and domain IV of ANX2 was stronger than the other combinations.

PMID- 9928991
TI  - The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB
      activation at the level of TRAF6.
AB  - The zinc finger protein A20 is encoded by an immediate early response gene whose
      expression is induced by different inflammatory stimuli, including interleukin-1
      (IL-1). Gene induction by IL-1 is mediated by activation of the transcription
      factor NF-kappaB, and requires the signal adapter protein TRAF6. The latter
      interacts with the NF-kappaB-inducing kinase NIK, which is believed to be part of
      the IkappaB kinase complex. Expression of A20 potently inhibits IL-1-induced NF
      kappaB activation by an unknown mechanism. Inhibition of IL-1-induced NF-kappaB
      activation was found to be mediated by the C-terminal zinc finger-containing
      domain of A20. More importantly, we present evidence that A20 interferes with IL
      1-induced NF-kappaB activation at the level of TRAF6, upstream of NIK. Moreover,
      A20 was shown to directly interact with TRAF6.

PMID- 9928992
TI  - Isolation and expression analysis of a novel human homologue of the Drosophila
      glial cells missing (gcm) gene.
AB  - A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM)
      was isolated using RACE. GCMB contained a gcm motif sequence and a nuclear
      targeting sequence similar to that of dGCM and mouse GCMb. Homology searches
      indicated that GCMB was located within chromosome 6p24.2. Transcripts of GCMB
      were detected by means of RT-PCR in fetal brain, normal adult kidney, 3/3
      medulloblastomas, 1/3 gliomas and 4/8 non-neuroepithelial tumor cell lines. Our
      data suggest that humans have two homologues of gcm like mice and that human gcm
      genes form a novel family which may function not only during fetal development
      but also in the postnatal or pathological stage.

PMID- 9928993
TI  - Formation of titanium(IV) transferrin by reaction of human serum apotransferrin
      with titanium complexes.
AB  - The reaction of human serum apotransferrin with titanium(IV) citrate under
      physiological conditions results in the formation of a specific bis-titanium(IV)
      transferrin adduct (Ti2Tf hereafter) with two titanium(IV) ions loaded at the
      iron binding sites. The same specific Ti2Tf complex is formed by reacting
      apotransferrin with titanium(III) chloride and exposing the sample to air. The
      derivative thus obtained was characterized by spectroscopic techniques, including
      absorption, UV difference, circular dichroism and 13C NMR spectroscopies, and
      shown to be stable within the pH range 5.5-9.0. Surprisingly, the reaction of
      apoTf with titanium(IV) nitrilotriacetate (NTA) does not lead to formation of
      appreciable amounts of Ti2Tf, even after long incubation times, although some
      weak interactions of Ti(IV)-NTA with apoTf are spectroscopically detected.
      Implications of the present results for a role of transferrin in the uptake,
      transport and delivery of soluble titanium(IV) compounds under physiological
      conditions are discussed.

PMID- 9928994
TI  - Inhibition of platelet aggregation by S-nitroso-cysteine via cGMP-independent
      mechanisms: evidence of inhibition of thromboxane A2 synthesis in human blood
      platelets.
AB  - S-Nitroso-cysteine (SNC), a putative endothelium-derived relaxing factor,
      potently inhibited collagen- and arachidonic acid-induced platelet aggregation
      (IC50=100 nM) and thromboxane A2 (TxA2) synthesis of human blood platelets. ODQ,
      a selective inhibitor of the soluble guanylyl cyclase, inhibited SNC-induced
      formation of cGMP but did not reverse inhibition by SNC of collagen- and
      arachidonic acid-induced platelet aggregation. Combination of ODQ with SQ-29548,
      a specific platelet TxA2 receptor antagonist, did not modify the antiaggregatory
      action of SNC. Our study shows that SNC inhibits platelet aggregation by cGMP
      independent mechanisms that may involve inhibition of TxA2 synthesis in human
      platelets.

PMID- 9928996
TI  - Evidence for calmodulin inter-domain compaction in solution induced by W-7
      binding.
AB  - Small-angle X-ray scattering and nuclear magnetic resonance were used to
      investigate the structural change of calcium-bound calmodulin (Ca2+/CaM) in
      solution upon binding to its antagonist, N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W-7). The radius of gyration was 17.4+/-0.3 A for
      Ca2+/CaM-W-7 with a molar ratio of 1:5 and 20.3+/-0.7 A for Ca2+/CaM. Comparison
      of the radius of gyration and the pair distance distribution function of the
      Ca2+/CaM-W-7 complex with those of other complexes indicates that binding of two
      W-7 molecules induces a globular shape for Ca2+/CaM, probably caused by an inter
      domain compaction. The results suggest a tendency for Ca2+/CaM to form a globular
      structure in solution, which is inducible by a small compound like W-7.

PMID- 9928995
TI  - Role of sympathetic activity in controlling the expression of vascular
      endothelial growth factor in brown fat cells of lean and genetically obese rats.
AB  - The thermogenic activity of brown adipose tissue (BAT) is heavily dependent on
      high perfusion, through its dense vascular system. Angiogenesis must go hand-in
      hand with BAT functions, but little is known about the factors controlling it. In
      the present study we demonstrate that: (a) vascular endothelial growth factor
      (VEGF) is synthesised and released in brown adipocytes in culture; (b) VEGF mRNA
      isoforms and protein appear in dispersed mature brown adipocytes and whole
      tissue; (c) VEGF expression is increased in BAT from cold-exposed rats, and in
      cultured brown adipocytes exposed to noradrenaline and the beta3-adrenoceptor
      agonists; (e) BAT from genetically obese (falfa) rats exhibits reduced expression
      of VEGF as well as a change in the ratio of mRNA isoforms. It is concluded that
      sympathetic control of VEGF expression via noradrenaline acting on beta3
      adrenoceptors plays a major role in developmental and adaptive angiogenesis, and
      defects in this contribute to the reduced thermogenic capacity of BAT in genetic
      obesity.

PMID- 9928997
TI  - Dermal fibroblast proliferation is improved by beta-catenin overexpression and
      inhibited by E-cadherin expression.
AB  - Several recent studies have shown that proteins of the cadherin-catenin complex
      are not only involved in cell-cell adhesion but also in the proliferation and
      differentiation processes. For the first time, we investigated the effect of the
      quantity of cytoplasmic beta-catenin on dermal fibroblast proliferation by
      overexpressing human beta-catenin in human dermal fibroblasts. Our results show
      that dermal fibroblasts overexpressing normal beta-catenin or a stabilized beta
      catenin mutant have a higher growth rate than control fibroblasts. Moreover, when
      confluence is reached, the number of fibroblasts is increased when the cells
      overexpress beta-catenin suggesting a role for beta-catenin in the regulation of
      contact growth arrest. Finally, by comparing proliferation in normal dermal
      fibroblasts and dermal fibroblasts expressing E-cadherin we observed a negative
      regulatory effect of E-cadherin expression on fibroblast proliferation. These
      data demonstrate the involvement of beta-catenin and cadherin in the dermal
      fibroblast proliferation process and in contact growth arrest.

PMID- 9928998
TI  - A recombinant single-chain antibody fragment that neutralizes toxin II from the
      venom of the scorpion Androctonus australis hector.
AB  - Monoclonal antibody 4C1 specifically binds to and neutralizes the most potent
      neurotoxin (AahII) of the scorpion Androctonus australis. The cDNAs encoding the
      variable regions of this antibody were isolated by PCR-mediated cloning. A single
      chain Fv gene was engineered and expressed in Escherichia coli. The recombinant
      protein had neutralizing activity similar to that of the intact antibody in vitro
      and in vivo. We have thus neutralized the pharmacological and biological
      properties of a scorpion neurotoxin with a single-chain Fv, which opens new
      perspectives for the treatment of envenomizations.

PMID- 9929000
TI  - The aminoacceptor stem of the yeast tRNA(Lys) contains determinants of
      mitochondrial import selectivity.
AB  - Yeast tRNA(Lys)CUU is nucleus-encoded and is partially imported into the
      mitochondria. Another lysine isoacceptor, tRNA(Lys)SUU, is also nucleus-encoded
      but is not imported. These two tRNAs differ in 21 bases. We have previously
      localised import selectivity determinants in the anticodon arm. By in vitro
      import of mutant transcripts and by expression of mutant tRNA genes in vivo we
      show here that the first base pair (1:72) and the discriminator base 73 are also
      relevant to import selectivity. Replacement of bases 1:72 in tRNA(Lys)SUU by
      those of tRNA(Lys)CUU makes it importable with a transport efficiency similar to
      natural.

PMID- 9928999
TI  - Transition protein 4 from boar late spermatid nuclei is a topological factor that
      stimulates DNA-relaxing activity of topoisomerase I.
AB  - Transition protein 4 (TP4) from boar late spermatid nuclei, having higher
      affinity for double-stranded DNA and a local melting activity of DNA, stimulated
      SV40 DNA-relaxing activity of eukaryotic topoisomerase I at TP4/DNA molar ratios
      of 6.6-11. A TP4-spermidine mixture stimulated the activity of topoisomerase I
      much more than spermidine alone, but no more than TP4 alone, and poly-L-arginine
      did not. These results suggest that TP4 contributes to the chromatin
      reorganization in the late spermatid nuclei from nucleosomal-type structure with
      negatively supercoiled DNA to nucleoprotamine structure with no supercoiled DNA.

PMID- 9929001
TI  - Purification of histidine tagged bacteriorhodopsin, pharaonis halorhodopsin and
      pharaonis sensory rhodopsin II functionally expressed in Escherichia coli.
AB  - Bacteriorhodopsin (BR) from Halobacterium salinarum as well as halorhodopsin
      (pHR) and sensory rhodopsin II (pSRII) from Natronobacterium pharaonis were
      functionally expressed in E. coli using the method of Shimono et al. IFEBS Lett.
      (1997) 420, 54-56]. The histidine tagged proteins were purified with yields up to
      1.0 mg/l cell culture and characterized by ESI mass spectrometry and their
      photocycle. The pSRII and pHR photocycles were indistinguishable from the wild
      type proteins. The BR photocycle was considerably prolonged. pSOII is located in
      the cytoplasmic membrane and the C-terminus is oriented towards the cytoplasm as
      determined by immunogold labelling.

PMID- 9929002
TI  - The Saccharomyces cerevisiae succinate-ubiquinone reductase contains a
      stoichiometric amount of cytochrome b562.
AB  - The Saccharomyces cerevisiae succinate-ubiquinone reductase or succinate
      dehydrogenase (SDH) is a tetramer of non-equivalent subunits encoded by the SDH1,
      SDH2, SDH3, and SDH4 genes. In most organisms, SDH contains one or two endogenous
      b-type hemes. However, it is widely believed that the yeast SDH does not contain
      heme. In this report, we demonstrate the presence of a stoichiometric amount of
      cytochrome b562 in the yeast SDH. The cytochrome is detected as a peak present in
      fumarate-oxidized, dithionite-reduced mitochondria. The peak is centered at 562
      nm and is present at a heme:covalent FAD molar ratio of 0.92+/-0.11. The
      cytochrome is not detectable in mitochondria isolated from SDH3 and SDH4 deletion
      strains. These observations strongly support our conclusion that cytochrome b562
      is a component of the yeast SDH.

PMID- 9929003
TI  - Dexamethasone modulation of multidrug transporters in normal tissues.
AB  - The expression of P-glycoprotein (P-gp) and canalicular multispecific organic
      anion transporter (cMOAT or Mrp2) was evaluated by Western blotting analysis of
      rat tissues isolated following daily administration (1 mg kg(-1) day(-1)) of
      dexamethasone over 4 days. Dexamethasone rapidly increased P-gp expression more
      than 4.5- and 2-fold in liver and lung, respectively, while it was decreased 40%
      in kidney. cMOAT expression was increased 2-fold in liver and kidney following
      dexamethasone treatment. The levels of both proteins returned to control values
      by 6 days after the conclusion of dexamethasone administration. These results
      indicate that dexamethasone can modulate P-gp and cMOAT expression in specific
      rat tissues and may have significant relevance for patients treated with
      dexamethasone as a single agent or in combination therapy with other drugs.

PMID- 9929004
TI  - 1H NMR spectroscopy of the binuclear Cu(II) active site of Streptomyces
      antibioticus tyrosinase.
AB  - The 600 MHz 1H NMR spectrum of tyrosinase (31 kDa) of Streptomyces antibioticus
      in the oxidized, chloride-bound form is reported. The downfield part of the
      spectrum (15-55 ppm) exhibits a large number of paramagnetically shifted signals.
      The paramagnetism is ascribed to a thermally populated triplet state. The signals
      derive from six histidines binding to the metals through their Nepsilon atoms.
      There is no evidence for endogenous bridges. The exchange coupling, -2J, amounts
      to 298 cm(-1). In the absence of chloride the peaks broaden. This is ascribed to
      a slowing down of the electronic relaxation. The exchange coupling decreases to 
      2J=103 cm(-1).

PMID- 9929005
TI  - Colocalization of phospholipase D1 and GTP-binding-defective mutant of ADP
      ribosylation factor 6 to endosomes and lysosomes.
AB  - Phospholipase D (PLD) is involved in various aspects of cellular function. Two
      isoforms, PLD1 and PLD2, have been identified. PLD1, which has two splicing
      variants, is regulated by various factors, including ADP-ribosylation factor
      (ARF). We here show that both variants of PLD1 are predominantly localized to
      late endosomes and lysosomes, but not to the Golgi apparatus or endoplasmic
      reticulum in contrast to earlier studies. Furthermore, PLD1s show significant
      colocalization with an ARF6 mutant defective in GTP binding. The data suggest
      that PLD1, under the regulation of ARF6, plays a role in the function of
      endosomes and lysosomes.

PMID- 9929006
TI  - Autolysis of bovine enteropeptidase heavy chain: evidence of fragment 118-465
      involvement in trypsinogen activation.
AB  - Variations in bovine enteropeptidase (EP) activity were shown to result from
      autolysis caused by the loss of calcium ions; the cleavage sites were determined.
      The native enzyme preferred its natural substrate, trypsinogen (KM=2.4 microM),
      to the peptide and fusion protein substrates (KM=200 and 125 microM,
      respectively). On the other hand, the truncated enzyme composed of the C-terminal
      fragment 466-800 of EP heavy chain and intact light chain did not distinguish
      these substrates. The results suggest that the N-terminal fragment 118-465 of the
      enteropeptidase heavy chain contains a secondary substrate-binding site that
      interacts directly with trypsinogen.

PMID- 9929007
TI  - Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1
      (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase
      activity.
AB  - Stx1 and Stx2 produced by Shiga toxin-producing Escherichia coli are cytotoxic
      due to their N-glycosidase activity on 28S rRNA. In this study, we have shown
      that proinflammatory cytokine mRNAs, especially IL-8, were induced by Stx1 and
      Stx2 in Caco-2 cells. A non-toxic mutant of Stxl which lacks N-glycosidase
      activity did not induce cytokine mRNAs. IL-8 production at the protein level was
      enhanced by Stx1 and Stx2, but not by the mutant Stx1. These results demonstrate
      that Shiga toxins induce expression and synthesis of cytokines in Caco-2 cells
      and their N-glycosidase activity is essential for the induction.

PMID- 9929008
TI  - Up-regulation of nuclear protein import by nuclear localization signal sequences
      in living cells.
AB  - Using an in vivo assay system, nuclear import ability in individual cells was
      determined by examining the nuclear import rate. It was found that when a small
      (not excess) amount of SV40 T-NLS peptides was co-injected, the nuclear import
      rate of SV40 T-NLS-containing substrates apparently increased. This up-regulation
      was reproduced by the co-injection of peptides containing bipartite type NLS of
      CBP80, but not mutated non-functional NLS peptides, which suggests that these
      phenomena are specific for functional NLSs. It was further shown that although,
      in growth-arrested cells, the nuclear import rate was down-regulated compared to
      growing cells, the elevation of the functional import rate by co-injected NLS
      peptides reached the same level as in proliferating cells. This up-regulation was
      abolished by the addition of a protein kinase inhibitor, staurosporine. These
      results suggest that although potential nuclear import ability does not vary in
      each cell, the rate of nuclear import may be controlled by the amount of
      karyophilic proteins, which need to be carried into the nucleus from the
      cytoplasm, possibly via an NLS-dependent phosphorylation reaction.

PMID- 9929009
TI  - Conformational stabilities of the rat alpha- and beta-parvalbumins.
AB  - It is widely believed that beta-parvalbumin (PV) isoforms are intrinsically less
      stable than alpha-parvalbumins, due to greater electrostatic repulsion and an
      abbreviated C-terminal helix. However, when examined by differential scanning
      calorimetry, the apo-form of the rat beta-PV (i.e. oncomodulin) actually displays
      greater thermal stability than the alpha-PV. Whereas the melting temperature of
      the a isoform is 45.8 degrees C at physiological pH and ionic strength, the Tm
      for the beta isoform is more than 7 degrees higher (53.6 degrees C). This result
      suggests that factors besides net charge and C-terminal helix length strongly
      influence parvalbumin conformational stability. Extension of the F helix in the
      beta-PV, by insertion of Ser-109, has a modest stabilizing effect, raising the
      Tm, by 1.1 degrees. Truncation of the alpha-PV F helix, by removal of Glu-108,
      has a more profound impact, lowering the Tm by 4.0 degrees.

PMID- 9929010
TI  - Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor
      which neutralizes granulocyte-macrophage colony stimulating factor.
AB  - Mice deficient in granulocyte-macrophage colony stimulating factor (GM-CSF)
      develop pulmonary alveolar proteinosis (PAP). We found that bronchoalveolar
      lavage fluid (BALF) from 11 patients with idiopathic pulmonary alveolar
      proteinosis (IPAP) suppressed the growth of peripheral blood monocytes and TF-1
      cells, a cell line dependent on either GM-CSF or interleukin-3 (IL-3). The
      inhibitory effect of PAP-BALF occurred only when TF-1 cells were cultured with GM
      CSF but not when cultured with IL-3, suggesting that PAP-BALF contains a factor
      that specifically interferes with GM-CSF function. 125I-GM-CSF binding to TF-1
      cells was prevented in the presence of BALF from IPAP patients. Furthermore,
      cross-linking of 125I-GM-CSF to IPAP-BALF produced two major bands on SDS-PAGE;
      these bands were not observed in normal BALF. These data suggest that IPAP is
      caused by expression of binding factor(s) which inhibit GM-CSF function in the
      lung.

PMID- 9929011
TI  - The horrors of Ashworth.

PMID- 9929012
TI  - The sacking of JAMA. Journal of the American Medical Association.

PMID- 9929013
TI  - Gambling with cardiovascular risk: picking the winners and the losers.

PMID- 9929014
TI  - Laser-scanning cytometry.

PMID- 9929015
TI  - Headache relief or impotence?

PMID- 9929016
TI  - Outstanding issues in use of disease-modifying agents in rheumatoid arthritis.

PMID- 9929017
TI  - Efficacy and safety of leflunomide compared with placebo and sulphasalazine in
      active rheumatoid arthritis: a double-blind, randomised, multicentre trial.
      European Leflunomide Study Group.
AB  - BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine
      synthesis, have shown efficacy in rheumatoid arthritis. This double-blind
      randomised trial compared leflunomide with placebo and sulphasalazine in active
      rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide
      (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g
      daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints
      were tender and swollen joint counts and investigator's and patient's overall
      assessments. Analyses were by intention to treat. FINDINGS: The mean changes in
      the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for
      tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and
      -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's
      overall assessment. Leflunomide and sulphasalazine were significantly superior to
      placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic
      disease progression was significantly slower with leflunomide and sulphasalazine
      than with placebo (p<0.01). Most common adverse events with leflunomide were
      diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently
      abnormal liver function was seen in three leflunomide-group patients and five
      sulphasalazine-group patients. There were two cases of reversible agranulocytosis
      in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than
      placebo in treatment of rheumatoid arthritis and showed similar efficacy to
      sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option
      as a disease-modifying antirheumatic drug.

PMID- 9929018
TI  - Comparison of radiation side-effects of conformal and conventional radiotherapy
      in prostate cancer: a randomised trial.
AB  - BACKGROUND: Radical radiotherapy is commonly used to treat localised prostate
      cancer. Late chronic side-effects limit the dose that can be given, and may be
      linked to the volume of normal tissues irradiated. Conformal radiotherapy allows
      a smaller amount of rectum and bladder to be treated, by shaping the high-dose
      volume to the prostate. We assessed the ability of this new technology to lessen
      the risk of radiation-related effects in a randomised controlled trial of
      conformal versus conventional radiotherapy. METHODS: We recruited men with
      prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy
      fractions. The men were randomly assigned conformal or conventional radiotherapy
      treatment. The primary endpoint was the development of late radiation
      complications (> 3 months after treatment) measured with the Radiation Therapy
      and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also
      recorded. FINDINGS: In the 225 men treated, significantly fewer men developed
      radiation-induced proctitis and bleeding in the conformal group than in the
      conventional group (37 vs 56% > or = RTOG grade 1, p=0.004; 5 vs 15% > or = RTOG
      grade 2, p=0.01). There were no differences between groups in bladder function
      after treatment (53 vs 59% > or = grade 1, p=0.34; 20 vs 23% > or = grade 2,
      p=0.61). After median follow-up of 3.6 years there was no significant difference
      between groups in local tumour control (conformal 78% [95% CI 66-86],
      conventional 83% [69-90]). INTERPRETATION: Conformal techniques significantly
      lowered the risk of late radiation-induced proctitis after radiotherapy for
      prostate cancer. Widespread introduction of these radiotherapy treatment methods
      is appropriate. Our results are the basis for dose-escalation studies to improve
      local tumour control.

PMID- 9929019
TI  - Effect of monochloramine disinfection of municipal drinking water on risk of
      nosocomial Legionnaires' disease.
AB  - BACKGROUND: Many Legionella infections are acquired through inhalation or
      aspiration of drinking water. Although about 25% of municipalities in the USA use
      monochloramine for disinfection of drinking water, the effect of monochloramine
      on the occurrence of Legionnaires' disease has never been studied. METHODS: We
      used a case-control study to compare disinfection methods for drinking water
      supplied to 32 hospitals that had had outbreaks of Legionnaires' disease with the
      disinfection method for water supplied to 48 control-hospitals, with control for
      selected hospital characteristics and water treatment factors. FINDINGS:
      Hospitals supplied with drinking water containing free chlorine as a residual
      disinfectant were more likely to have a reported outbreak of Legionnaires'
      disease than those that used water with monochloramine as a residual disinfectant
      (odds ratio 10.2 [95% CI 1.4-460]). This result suggests that 90% of outbreaks
      associated with drinking water might not have occurred if monochloramine had been
      used instead of free chlorine for residual disinfection (attributable proportion
      0.90 [0.29-1.00]). INTERPRETATION: The protective effect of monochloramine
      against legionella should be confirmed by other studies. Chloramination of
      drinking water may be a cost-effective method for control of Legionnaires'
      disease at the municipal level or in individual hospitals, and widespread
      implementation could prevent thousands of cases.

PMID- 9929020
TI  - Indications for cholesterol-lowering medication: comparison of risk-assessment
      methods.
AB  - BACKGROUND: Recommendations for the prescription of lipid-lowering drugs
      emphasise the importance of an assessment of absolute coronary heart disease
      (CHD) risk based on all risk factors, rather than simply the serum cholesterol
      concentration. If, however, the methods recommended for risk assessment are
      inaccurate, recommended prescribing will not occur. We compared several sets of
      guidelines for such treatment in a series of patients referred to a lipid clinic,
      to assess the difference in degree of risk of CHD at which lipid-lowering
      medication is recommended by each set of guidelines. METHODS: For a series of 570
      patients (50% men) without pre-existing clinical evidence of atherosclerosis
      referred to a lipid clinic, we compared the algorithms, charts, and tables used
      by the US National Cholesterol Education Program (NCEP), the joint guidelines of
      the European Society of Cardiology, the European Atherosclerosis Society, and the
      European Society of Hypertension, and the report of the UK Standing Medical
      Advisory Committee with the Framingham risk equation programmed into a computer.
      FINDINGS: In 386 patients for whom the NCEP and UK guidelines could be compared,
      62% of the men and 72% of the women met NCEP criteria for lipid-lowering
      medication, whereas only 9% of the men and less than 1% of the women met the UK
      criteria. The Framingham equation estimated a CHD risk of more than 3% per year
      in 22% of the men and 7% of the women, which shows that the UK tables
      underestimated CHD risk. European guidelines could be applied to only 261
      patients, and were reasonably accurate in assessment of a CHD risk of 2% per
      year. INTERPRETATION: Guidelines for the use of statin treatment in patients with
      CHD differ in their assessment of CHD risk. The method of risk assessment
      recommended in future guidelines for CHD prevention should be critically tested
      in relevant groups of patients.

PMID- 9929021
TI  - Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular
      disease: a randomised trial.
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial
      atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent
      placement (PTAS) may be more effective. We undertook a randomised prospective
      study to compare PTA with PTAS in patients with ostial atherosclerotic renal
      artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery
      stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA
      failed immediately or during 6 months' follow-up. Analysis was by intention to
      treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one
      patient in the PTAS group was excluded from the study. Primary success rate (<50%
      residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients)
      for PTAS (difference between groups 31% [95% CI 12-50]). Complications were
      similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and
      75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary
      procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12
      patients underwent secondary stenting for primary or late failure of PTA within
      the follow-up period: success was similar to that of primary PTAS. Evaluation
      based on intention to treat showed no difference in clinical results at six
      months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to
      achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary
      PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However,
      the burden of reintervention after PTA outweighs the potential saving in stents,
      so primary PTAS is a better approach to use.

PMID- 9929022
TI  - Effect of inhibition of nitric oxide synthase on chronic tension-type headache: a
      randomised crossover trial.
AB  - BACKGROUND: Studies in animals have shown that nitric oxide plays an important
      part in central sensitisation and that inhibitors of nitric oxide synthase (NOS)
      decrease sensitisation in models of persistent pain. The efficacy of inhibitors
      of NOS has not been tested in patients with tension-type chronic headache. We
      aimed to show whether N(G)-monomethyl-L-arginine hydrochloride (L-NMMA), an
      inhibitor of NOS, is effective in relieving pain in such patients. METHODS: We
      undertook a randomised double-blind, crossover trial of 16 patients with chronic
      tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L
      NMMA or placebo on 2 days separated by at least 1 week in a randomised order.
      Headache intensity was measured on a 100 mm visual analogue scale, and on a
      verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of
      treatment. The primary endpoint was reduction of pain intensity on the visual
      analogue scale by the active treatment compared with placebo. FINDINGS: L-NMMA
      reduced pain intensity on the visual analogue scale significantly more than
      placebo: 120 min after start of treatment, the mean pain score was decreased from
      49 to 33 with L-NMMA and from 44 to 40 with placebo (p=0.01). Pain intensity on
      the verbal rating scale was also significantly lower for treatment with L-NMMA
      than for treatment with placebo (p=0.02). INTERPRETATION: Inhibition of NOS had
      an analgesic effect in chronic tension-type headache. Further tests are required
      before clinical application.

PMID- 9929023
TI  - The importance of reading test results.

PMID- 9929024
TI  - Intuitive hypertext-based molecular identification of micro-organisms.

PMID- 9929025
TI  - Twinning and folic acid use.

PMID- 9929026
TI  - Periconceptional folic acid intake in Nijmegen, Netherlands.

PMID- 9929027
TI  - Acquired activated protein-C resistance in pregnancy and association with
      increased thrombin generation and fetal weight.

PMID- 9929028
TI  - Effects of peripheral stem-cell or bone-marrow reinfusion on peripheral serotonin
      metabolism.

PMID- 9929029
TI  - Improvement in renal function in hepatorenal syndrome with N-acetylcysteine.

PMID- 9929030
TI  - Acute fatty liver after malaria prophylaxis with mefloquine.

PMID- 9929031
TI  - Healing of rickets after calcium supplementation.

PMID- 9929032
TI  - False-positive rapid tests for malaria in patients with rheumatoid factor.

PMID- 9929033
TI  - Limitation of eye movement in merosin-deficient congenital muscular dystrophy.

PMID- 9929034
TI  - Non-invasive evaluation of shoulder problems after stroke.

PMID- 9929035
TI  - Nuclear-test-veterans'survey prompts official inquiries.

PMID- 9929037
TI  - In-vitro fertilisation guidelines fall behind the times.

PMID- 9929036
TI  - Male contraceptive research steps back into spotlight.

PMID- 9929038
TI  - Bovine somatotropin--who's crying over spilt milk?

PMID- 9929039
TI  - COX-2 inhibitors.
AB  - In the past 100 years aspirin has demonstrated its value as an analgesic, anti
      inflammatory, and antithrombotic agent. However, by 1938, it was clear that
      aspirin was gastrotoxic. Non-steroidal anti-inflammatory drugs (NSAIDs),
      developed since the 1960s, failed to achieve the goal of "a safer aspirin". The
      demonstration that inhibition of prostaglandin synthesis via a cyclo-oxygenase
      (COX) enzyme was central to both the therapeutic and toxic effects of aspirin and
      non-aspirin NSAIDs appeared to establish the principle of no gain without pain.
      This link may have been broken by drugs that selectively inhibit the inducible
      COX-2 enzyme. The COX enzyme is now a target of drug interventions against the
      inflammatory process. Might the "safe aspirin" be here at last?

PMID- 9929040
TI  - Making Cairo work.
AB  - The 1994 International Conference on Population and Development set broad new
      goals for family planning and reproductive health. The resources available to
      fund these much needed programmes, however, are much smaller than was originally
      calculated. To divide the limited budgets for the maximum health impact, likely
      resource flows need to be set against the cost of various family planning and
      reproductive health interventions. Preliminary analysis suggests that selection
      of cost-effective delivery of family planning services would still meet much of
      the need for family planning, and that some progress could be made towards
      improved control of sexually transmitted diseases.

PMID- 9929041
TI  - Periodic chest radiography: unnecessary, expensive, but still pervasive.

PMID- 9929042
TI  - Long-term results of RITA-1.

PMID- 9929043
TI  - Paraquat poisoning.

PMID- 9929044
TI  - Paraquat poisoning.

PMID- 9929045
TI  - Paraquat poisoning.

PMID- 9929046
TI  - Ageing and cardiovascular disease in developing countries.

PMID- 9929047
TI  - Thalidomide in toxic epidermal necrolysis.

PMID- 9929048
TI  - Thalidomide in toxic epidermal necrolysis.

PMID- 9929049
TI  - Provider-to-patient transmission of hepatitis B virus.

PMID- 9929050
TI  - Management of hyperemesis in pregnant women.

PMID- 9929051
TI  - Management of hyperemesis in pregnant women.

PMID- 9929052
TI  - Abnormal potassium-channel function in platelets in Alzheimer's disease.

PMID- 9929053
TI  - Abnormal potassium-channel function in platelets in Alzheimer's disease.

PMID- 9929054
TI  - Panic disorder.

PMID- 9929055
TI  - Feeding a weaning infant.

PMID- 9929056
TI  - Packed-cell volume and haemoglobin in elite athletes.

PMID- 9929057
TI  - Adjuvant therapy of cutaneous melanoma.

PMID- 9929058
TI  - European centre for infectious disease.

PMID- 9929059
TI  - European centre for infectious disease.

PMID- 9929060
TI  - Detention of potentially dangerous people.

PMID- 9929061
TI  - Medical records.

PMID- 9929062
TI  - Internet and European drug regulation.

PMID- 9929063
TI  - Internet accelerates spread of bogus cancer cure.

PMID- 9929064
TI  - Technology and art against cancer.

PMID- 9929065
TI  - The Nobel chronicles. 1935: Hans Spemann (1869-1941).

PMID- 9929066
TI  - New perspectives on glaucoma.

PMID- 9929067
TI  - HIV drug resistance testing shows promise.

PMID- 9929068
TI  - Ultrasound may markedly improve cancer detection in dense breasts.

PMID- 9929069
TI  - Advisory board aims to develop pragmatic public health policies.

PMID- 9929070
TI  - Diet supplement data on the Internet.

PMID- 9929071
TI  - From the Centers for Disease Control and Prevention. Transmission of measles
      among a highly vaccinated school population--Anchorage, Alaska, 1998.

PMID- 9929072
TI  - From the Centers for Disease Control and Prevention. Preemptive state tobacco
      control laws--United States, 1982-1998.

PMID- 9929073
TI  - From the Centers for Disease Control and Prevention. Update: multistate outbreak
      of listeriosis--United States, 1998-1999.

PMID- 9929074
TI  - From the Centers for Disease Control and Prevention. Nosocomial Burkholderia
      cepacia infection and colonization associated with intrinsically contaminated
      mouthwash--Arizona, 1998.

PMID- 9929075
TI  - Time for action on drug safety.

PMID- 9929076
TI  - Time for action on drug safety.

PMID- 9929077
TI  - Time for action on drug safety.

PMID- 9929078
TI  - The role of alcohol and social stress in Russia's mortality rate.

PMID- 9929079
TI  - Words in "In a word".

PMID- 9929080
TI  - Words in "In a word".

PMID- 9929081
TI  - Firearm-related homicides among teenagers and young adults.

PMID- 9929082
TI  - Firearm-related homicides among teenagers and young adults.

PMID- 9929083
TI  - Health and human rights in the medical school curriculum.

PMID- 9929084
TI  - Cancer mortality after nonmelanoma skin cancer.

PMID- 9929085
TI  - Comparison of lifestyle and structured interventions to increase physical
      activity and cardiorespiratory fitness: a randomized trial.
AB  - CONTEXT: Even though the strong association between physical inactivity and ill
      health is well documented, 60% of the population is inadequately active or
      completely inactive. Traditional methods of prescribing exercise have not proven
      effective for increasing and maintaining a program of regular physical activity.
      OBJECTIVE: To compare the 24-month intervention effects of a lifestyle physical
      activity program with traditional structured exercise on improving physical
      activity, cardiorespiratory fitness, and cardiovascular disease risk factors.
      DESIGN: Randomized clinical trial conducted from August 1, 1993, through July 31,
      1997. PARTICIPANTS: Sedentary men (n = 116) and women (n = 119) with self
      reported physical activity of less than 36 and 34 kcal/kg per day, respectively.
      INTERVENTIONS: Six months of intensive and 18 months of maintenance intervention
      on either a lifestyle physical activity or a traditional structured exercise
      program. MAIN OUTCOME MEASURES: Primary outcomes were physical activity assessed
      by the 7-Day Physical Activity Recall and peak oxygen consumption (VO2peak) by a
      maximal exercise treadmill test. Secondary outcomes were plasma lipid and
      lipoprotein cholesterol concentrations, blood pressure, and body composition. All
      measures were obtained at baseline and at 6 and 24 months. RESULTS: Both the
      lifestyle and structured activity groups had significant and comparable
      improvements in physical activity and cardiorespiratory fitness from baseline to
      24 months. Adjusted mean changes (95% confidence intervals [CIs]) were 0.84 (95%
      CI, 0.42-1.25 kcal/kg per day; P<.001) and 0.69 (95% CI, 0.25-1.12 kcal/kg day; P
      = .002) for activity, and 0.77 (95% CI, 0.18-1.36 mL/kg per minute; P = .01) and
      1.34 (95% CI, 0.72-1.96 mL/kg per minute; P<.001) for VO2peak for the lifestyle
      and structured activity groups, respectively. There were significant and
      comparable reductions in systolic blood pressure (-3.63 [95% CI, -5.54 to -1.72
      mm Hg; P<.001] and -3.26 [95% CI, -5.26 to -1.25 mm Hg; P = .002]) and diastolic
      blood pressure (-5.38 [95% CI, -6.90 to -3.86 mm Hg; P<.001] and -5.14 [95% CI, 
      6.73 to -3.54 mm Hg; P<.001) for the lifestyle and structured activity groups,
      respectively. Neither group significantly changed their weight (-0.05 [95% CI, 
      1.05 to 0.96 kg; P = .93] and 0.69 [95% CI, -0.37 to 1.74 kg; P = .20]), but each
      group significantly reduced their percentage of body fat (-2.39% [95% CI, -2.92%
      to -1.85%; P<.001] and -1.85% [95% CI, -2.41 % to -1.28%; P<.001]) in the
      lifestyle and structured activity groups, respectively. CONCLUSIONS: In
      previously sedentary healthy adults, a lifestyle physical activity intervention
      is as effective as a structured exercise program in improving physical activity,
      cardiorespiratory fitness, and blood pressure.

PMID- 9929086
TI  - Effects of lifestyle activity vs structured aerobic exercise in obese women: a
      randomized trial.
AB  - CONTEXT: Physical inactivity contributes to weight gain, but only 22% of
      Americans are regularly active. OBJECTIVE: To examine short- and long-term
      changes in weight, body composition, and cardiovascular risk profiles produced by
      diet combined with either structured aerobic exercise or moderate-intensity
      lifestyle activity. DESIGN: Sixteen-week randomized controlled trial with 1-year
      follow-up, conducted from August 1995 to December 1996. PARTICIPANTS AND SETTING:
      Forty obese women (mean body mass index [weight in kilograms divided by the
      square of height in meters], 32.9 kg/m2; mean weight, 89.2 kg) with a mean age of
      42.9 years (range, 21-60 years) seen in a university-based weight management
      program. INTERVENTIONS: Structured aerobic exercise or moderate lifestyle
      activity; low-fat diet of about 1200 kcal/d. MAIN OUTCOME MEASURES: Changes in
      body weight, body composition, cardiovascular risk profiles, and physical fitness
      at 16 weeks and at 1 year. RESULTS: Mean (SD) weight losses during the 16-week
      treatment program were 8.3 (3.8) kg for the aerobic group and 7.9 (4.2) kg for
      the lifestyle group (within groups, P<.001; between groups, P = .08). The aerobic
      group lost significantly less fat-free mass (0.5 [1.3] kg) than the lifestyle
      group (1.4 [1.3] kg; P = .03). During the 1-year follow-up, the aerobic group
      regained 1.6 [5.5] kg, while the lifestyle group regained 0.08 (4.6) kg. At week
      16, serum triglyceride levels and total cholesterol levels were reduced
      significantly (P<.001) from baseline (16.3% and 10.1% reductions, respectively)
      but did not differ significantly between groups and were not different from
      baseline or between groups at week 68. CONCLUSIONS: A program of diet plus
      lifestyle activity may offer similar health benefits and be a suitable
      alternative to diet plus structured aerobic activity for obese women.

PMID- 9929087
TI  - Parkinson disease in twins: an etiologic study.
AB  - CONTEXT: The cause of Parkinson disease (PD) is unknown. Genetic linkages have
      been identified in families with PD, but whether most PD is inherited has not
      been determined. OBJECTIVE: To assess genetic inheritance of PD by studying
      monozygotic (MZ) and dizygotic (DZ) twin pairs. DESIGN: Twin study comparing
      concordance rates of PD in MZ and DZ twin pairs. SETTING AND PARTICIPANTS: A
      total of 19842 white male twins enrolled in the National Academy of
      Sciences/National Research Council World War II Veteran Twins Registry were
      screened for PD and standard diagnostic criteria for PD were applied. Zygosity
      was determined by polymerase chain reaction or questionnaire. MAIN OUTCOME
      MEASURE: Parkinson disease concordance in twin pairs, stratified by zygosity and
      age at diagnosis. RESULTS: Of 268 twins with suspected parkinsonism and 250
      presumed unaffected twin brothers, 193 twins with PD were identified (concordance
      adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete
      diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ;
      relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with
      diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4
      pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69
      21.26). CONCLUSIONS: The similarity in concordance overall indicates that genetic
      factors do not play a major role in causing typical PD. No genetic component is
      evident when the disease begins after age 50 years. However, genetic factors
      appear to be important when disease begins at or before age 50 years.

PMID- 9929088
TI  - Cost-effectiveness of 3 methods to enhance the sensitivity of Papanicolaou
      testing.
AB  - CONTEXT: ThinPrep, AutoPap, and Papnet are 3 new technologies that increase the
      sensitivity and cost of cervical cancer screening. OBJECTIVE: To estimate the
      cost-effectiveness of these technological enhancements to Papanicolaou (Pap)
      tests. DESIGN: We estimated the increase in sensitivity from using these
      technologies by combining results of 8 studies meeting defined criteria. We used
      published literature and additional sources for cost estimates. To estimate
      overall cost-effectiveness, we applied a 9-state time-varying transition state
      model to these data and information about specific populations. SETTING: A
      hypothetical program serving a cohort of 20- to 65-year-old women who begin
      screening at the same age and are representative of the US population. RESULTS:
      The new technologies increased life expectancy by 5 hours to 1.6 days, varying
      with the technology and the frequency of screening. All 3 technologies also
      increased the cost per woman screened by $30 to $257 (1996 US dollars). AutoPap
      dominated ThinPrep in the base case. At each screening interval, AutoPap
      increased survival at the lowest cost. The cost per year of life saved rose from
      $7777 with quadrennial screening to $166000 with annual screening. Papnet
      produced more life-years at a higher cost per year of life saved. However, when
      used with triennial screening, each of them produced more life-years at lower
      cost than conventional Pap testing every 2 years. The cost-effectiveness ratio of
      each technology improved with increases in the prevalence of disease, decreases
      in the sensitivity of conventional Pap testing, and increases in the improvement
      in sensitivity produced by the technology. CONCLUSIONS: Technologies to increase
      the sensitivity of Pap testing are more cost-effective when incorporated into
      infrequent screening. Increases in sensitivity and decreases in cost may
      eventually make each technology more cost-effective.

PMID- 9929090
TI  - Access to essential drugs in poor countries: a lost battle?
AB  - Drugs offer a simple, cost-effective solution to many health problems, provided
      they are available, affordable, and properly used. However, effective treatment
      is lacking in poor countries for many diseases, including African
      trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bacterial
      meningitis. Treatment may be precluded because no effective drug exists, it is
      too expensive, or it has been withdrawn from the market. Moreover, research and
      development in tropical diseases have come to a near standstill. This article
      focuses on the problems of access to quality drugs for the treatment of diseases
      that predominantly affect the developing world: (1) poor-quality and counterfeit
      drugs; (2) lack of availability of essential drugs due to fluctuating production
      or prohibitive cost; (3) need to develop field-based drug research to determine
      optimum utilization and remotivate research and development for new drugs for the
      developing world; and (4) potential consequences of recent World Trade
      Organization agreements on the availability of old and new drugs. These problems
      are not independent and unrelated but are a result of the fundamental nature of
      the pharmaceutical market and the way it is regulated.

PMID- 9929089
TI  - Reduced quality of life in survivors of acute respiratory distress syndrome
      compared with critically ill control patients.
AB  - CONTEXT: Health-related quality of life (HRQL) is reduced in patients who survive
      acute respiratory distress (ARDS), but whether this decline in HRQL is caused by
      ARDS or other aspects of the patient's illness or injury is unknown. OBJECTIVE:
      To determine if there are differences in the HRQL of ARDS survivors and
      comparably ill or injured controls without ARDS. DESIGN: Prospective, matched,
      parallel cohort study. SETTING: A 411-bed municipal medical and regional level I
      trauma center. PATIENTS: Seventy-three pairs of ARDS survivors and severity
      matched controls with the clinical risk factors for ARDS of sepsis and trauma
      admitted between January 1, 1994, and July 30, 1996. MAIN OUTCOME MEASURES: The
      HRQL of ARDS survivors and controls, assessed by generic and pulmonary disease
      specific HRQL instruments (Medical Outcomes Study 36-Item Short Form Health
      Survey, Standard Form [SF-36] and St George's Respiratory Questionnaire [SGRQ],
      respectively). RESULTS: Clinically meaningful and statistically significant
      reductions in HRQL scores of ARDS survivors (n = 73) were seen in 7 of 8 SF-36
      domains and 3 of 3 SGRQ domains compared with matched controls (P<.001 for all
      reductions). The largest decrements in the HRQL were seen in physical function
      and pulmonary symptoms and limitations. Analysis of trauma-matched pairs (n = 46)
      revealed significant reductions in 7 of 8 SF-36 domains (P< or =.02) and 3 of 3
      SGRQ domains (P< or =.003). Analysis of sepsis-matched pairs (n = 27) revealed
      significant reductions in 6 of 8 SF-36 domains (P< or =.05) and 3 of 3 SGRQ
      domains (P< or =.002). CONCLUSIONS: Survivors of ARDS have a clinically
      significant reduction in HRQL that appears to be caused exclusively by ARDS and
      its sequelae. Reductions were primarily noted in physical functioning and
      pulmonary disease-specific domains.

PMID- 9929091
TI  - A 45-year-old woman with premenstrual dysphoric disorder.

PMID- 9929092
TI  - A 40-year-old woman considering contraception, 1 year later.

PMID- 9929093
TI  - Benefits of lifestyle activity vs structured exercise.

PMID- 9929094
TI  - Understanding Parkinson disease.

PMID- 9929095
TI  - Direct-to-consumer prescription drug advertising builds bridges between patients
      and physicians.

PMID- 9929097
TI  - JAMA patient page: exercise.

PMID- 9929096
TI  - Direct-to-consumer marketing of prescription drugs: creating consumer demand.

PMID- 9929098
TI  - Acute promyelocytic leukemia: all-trans retinoic acid (ATRA) along with
      chemotherapy is superior to ATRA alone.
AB  - This study was conducted to compare the results of treatment of acute
      promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a
      combination therapy of ATRA followed by chemotherapy. Forty-three patients
      treated between February 1992 and February 1996 were included in this study.
      Eighteen patients were treated with ATRA alone and 25 patients were treated with
      ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients
      at presentation, following treatment, and at follow-up. A complete response (CR)
      was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by
      chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with
      median survival of eight months (range, 1 to 28). One patient died of hepatitis
      in CR and one patient is alive 2 years after diagnosis. In the combination
      therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6
      to 56 months). After achieving a CR, four patients died due to infections during
      chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic
      response was seen in 8 of the 10 patients in whom cytogenetic data was available
      after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom
      data was available showed a major cytogenetic response after treatment with ATRA
      plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the
      percentage of t(15;17) cells in the marrow. Patients with a complete
      hematological response but no cytogenetic response relapsed within six months.
      Ten patients died prior to response evaluation. Two patients who received ATRA
      died of retinoic acid syndrome, one of pneumonia, and one of intracranial
      hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic
      acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular
      failure. Only one patient is alive at 24 months following treatment with ATRA
      alone. The relapse-free survival is 42% at four years for patients treated with
      ATRA followed by chemotherapy. This trial is a historical comparison of ATRA
      alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial
      shows a significant improvement in the event free survival of patients receiving
      chemotherapy as consolidation following ATRA.

PMID- 9929099
TI  - Increased truncated form of plasma tissue factor pathway inhibitor levels in
      patients with disseminated intravascular coagulation.
AB  - To evaluate that the relationship between the truncated form of tissue factor
      pathway inhibitor (TFPI) and the stage of disseminated intravascular coagulation
      (DIC), we measured the plasma levels of tissue factor (TF) antigen and the intact
      and truncated forms of TFPI antigens in 41 patients with DIC, 12 with pre-DIC,
      and 20 with non-DIC. The plasma TF and total TFPI antigen levels were
      significantly higher in patients with DIC than in non-DIC patients. Plasma levels
      of intact TFPI antigen in the pre-DIC groups were significantly lower than in the
      non-DIC and DIC groups. The truncated form of TFPI antigen levels in DIC patients
      were significantly increased compared with those in non-DIC and pre-DIC patients.
      The fact that the intact form of TFPI was decreased in pre-DIC patients compared
      with that in non-DIC patients, suggests that it is consumed in the pre-DIC state
      and that hypercoagulability occurs in pre-DIC patients. The increased level of
      the truncated form of TFPI in DIC patients may be attributed to proteolysis of
      the intact form of TFPI in these patients. The increased level of the truncated
      form of TFPI may be a useful index for the diagnosis of DIC.

PMID- 9929100
TI  - Epstein-Barr virus infection in Richter's transformation.
AB  - Chronic lymphocytic leukemia (CLL) may convert to a diffuse large cell lymphoma
      (Richter's syndrome) over time. In occasional cases of Richter's transformation,
      Epstein-Barr virus (EBV) has been identified in the lymphoma cells. To evaluate
      the association of EBV infection with Richter's syndrome, the biopsy specimens
      and clinical records of 25 patients who were seen at the Mayo Clinic between 1984
      1996 were retrospectively evaluated for the presence of EBV by immunoperoxidase
      staining for expression of EBV latent membrane protein (LMP), as well as the
      expression of EBV RNA and DNA in the cells by in situ hybridization. Four of the
      25 patients showed evidence of EBV in the diffuse large cell lymphoma cells-three
      patients with a B-cell phenotype were positive for LMP, EBV DNA, and RNA; and one
      patient with a T-cell phenotype had positive EBV RNA in the large cell lymphoma
      cells. The Richter's syndrome was treated with combination chemotherapy in 15
      patients, three received radiotherapy, three were followed without further
      therapy after a splenectomy, two died before treatment could be started, and one
      patient had insufficient follow-up. One patient with evidence of EBV in large
      cell lymphoma cells was treated with acyclovir as initial therapy. The median
      survival of EBV-positive patients was three months compared with nine months for
      EBV-negative patients, but this difference was not statistically significant (P =
      0.385). Evidence for EBV infection related to Richter's transformation was
      present in 16% of the patients in this study and may be associated with a poorer
      outcome. Primary therapy with acyclovir in one patient did not seem to be
      beneficial and other therapeutic modalities in patients with EBV-positive
      Richter's transformation need to be explored.

PMID- 9929101
TI  - Circulating cytokines response and the level of erythropoiesis in sickle cell
      anemia.
AB  - A hemoglobin F (HbF) level between eight and nine percent divides sickle cell
      anemia (SS) patients into two populations, according to the kinetics of
      circulating burst forming units-erythroid (BFU-E), long term culture-initialing
      cells (LTC-IC), and cytokine plasma concentrations. The SS patients with HbF
      levels lower than 8-9% are more anemic (LFSS patients) than those with HbF levels
      higher than 8-9% who have less severe anemia (HFSS patients). We report here that
      the level of erythropoiesis [evaluated by the levels of soluble transferin
      receptors (sTfR)] is not identical in these two patient populations, supporting
      the idea that a different set of regulatory mechanisms might be required to
      maintain the two levels of increased hematopoiesis. The plasma sTfR concentration
      was increased in all SS samples compared with controls (P < 0.002) and sTfR
      levels were negatively correlated with peripheral HbF%. (r = -0.574, P < 0.002).
      Furthermore, sTfR levels were higher in LFSS than in HFSS patients.
      Erythropoietin (Epo) levels were increased in the plasma of LFSS individuals
      (range = 34-215 ml U/ml), while the values in HFSS patients were in the normal
      range (3-20 ml U/ml). Furthermore, we identify here stem cell factor (SCF) and
      transforming growth factor-beta (TGF-beta) as regulatory factors specifically
      affected by the presence of SS genotype and its level of severity. The plasma
      concentrations of SCF and TGF-beta were increased compared with normal controls
      and high levels of SCF (up to 7,000 pg/ml) were detected in LFSS patients. The
      latter also showed increased proportion of SCF+ CD34 enriched circulating cells
      (49%). Low SCF in HFSS patients is associated with elevated TGF-beta, suggesting
      a regulatory role of the latter on either SCF release or c-kit expression in
      progenitor cells. Occasional elevation of granulocyte macrophage-colony
      stimulating factor (G-CSF), interleukin (IL)-7, and macrophage inflammatory
      protein (MIP)-1alpha in plasma of SS patients is not specific because no relation
      to HbF could be demonstrated. All plasma tested for leukemia inhibitory factor
      (LIF) were negative. Data presented here, complementing previously published
      information, supports a model in which HFSS patients achieve a balance between
      inhibitory (TGF-beta) and stimulatory (SCF, IL-3) factors, resulting in moderate
      erythropoietic response. In contrast, in LFSS patients, low levels of TGF-beta
      and the increased release of GM-CSF and SCF maintain the intense erythropoiesis
      in response to higher erythropoietic stress, in these more severe patients.

PMID- 9929102
TI  - Schistocytosis and a thrombotic microangiopathy-like syndrome in hospitalized HIV
      infected patients.
AB  - Approximately 150 human immunodeficiency virus (HIV)-infected patients with a
      thrombotic microangiopathy (TMA)-like syndrome have been reported in the
      literature since the early 1980s. The prevalence of a TMA-like syndrome in our
      hospitalized patients was determined to discern whether it is a more common
      occurrence than previously recognized and, if possible, to delineate risk factors
      for its occurrence. A total of 350 patients admitted consecutively to the Johns
      Hopkins Hospital HIV inpatient service were assessed from May 1, 1996 through
      February 1, 1997. These patients were evaluated for the presence of anemia,
      thrombocytopenia, fragmented erythrocytes on peripheral blood smear
      (schistocytosis), renal dysfunction, neurologic dysfunction, and fever. The
      association of a TMA-like syndrome with demographic and clinical factors was
      analyzed. Schistocytosis was present in 24% of the patients and a TMA-like
      syndrome (anemia, thrombocytopenia, schistocytosis + renal dysfunction or
      neurologic dysfunction, and fever) was present in 7% of the patients. The
      patients who had a TMA-like syndrome were more likely to have a low CD4
      lymphocyte count or CD4 percentage, Centers for Disease Control and Prevention
      stage C disease, and have bacterial sepsis. Age, race, HIV risk group, other
      diagnoses, and prescribed drugs were not associated. Patients were more likely to
      die if they had a TMA-like syndrome, independently of level of immunosuppression.
      Schistocytosis and a TMA-like syndrome are relatively common in hospitalized HIV
      infected patients. This syndrome may contribute to mortality and morbidity,
      particularly in patients with more advanced disease.

PMID- 9929103
TI  - Serum transferrin receptor as a marker of erythropoiesis suppression in patients
      on chronic transfusion.
AB  - In the management of patients requiring chronic transfusion, various parameters
      may be used to evaluate the degree of erythroid marrow suppression. The aim of
      our study was to assess which of these parameters provide the most useful
      assessment of erythropoiesis. We studied 27 chronically transfused patients, 19
      with sickle cell disease (SS patients) and 8 with thalassemia. Thirty-one
      nonchronically transfused SS patients and 74 healthy children served as controls.
      We measured serum transferrin receptor levels, reticulocyte counts, hemoglobin
      (Hb) concentrations and erythropoietin levels. The serum transferrin receptor
      levels were very elevated in control SS patients and remained significantly
      elevated in those on transfusion therapy, but were normal in thalassemia
      patients, indicating a more complete suppression of erythropoiesis. The
      reticulocyte counts were elevated in all SS patients, even when on chronic
      transfusion, but were in the normal range in patients with thalassemia.
      Erythropoietin levels were elevated in patients with thalassemia and in all the
      SS patients. Hb levels negatively correlated with serum transferrin receptor and
      erythropoietin in all SS patients. In the transfused SS patients, a higher HbS
      level correlated with higher reticulocyte counts, transferrin receptor, and
      erythropoietin levels. In thalassemia patients, erythropoiesis was more
      completely suppressed, as reflected both by normal reticulocyte counts and near
      normal transferrin receptor levels. Though the reticulocyte counts were not
      significantly different in the transfused SS patients, the serum transferrin
      receptor levels were less elevated than in SS patients not on transfusion. The
      serum transferrin receptor level appears to be the most useful marker of marrow
      erythropoietic activity in chronically transfused SS patients. We recommend that
      reticulocyte counts be integrated with periodic measurements of serum transferrin
      receptor levels.

PMID- 9929104
TI  - A novel and de novo spontaneous point mutation (Glu271STOP) of the antithrombin
      gene results in a type I deficiency and thrombophilia.
AB  - We describe a novel, de novo point mutation in one antithrombin (AT) allele
      resulting in type I AT deficiency and thrombophilia. Low plasma AT activity as
      well as low plasma AT antigen were documented in the propositus, but not in the
      parents, or in a male sibling. AT gene analysis by sequencing polymerase chain
      reaction-amplified genomic DNA from exon 5 of the propositus revealed a novel
      point mutation, GAG-->TAG at codon 271, resulting in a stop codon (Glu271STOP).
      This mutation was not demonstrable in the other members of his immediate family.
      DNA marker polymorphism analysis indicated the expected parentage. Based on
      allele frequency data for Caucasians in the United States the cumulative
      paternity index, or CPI, for the propositus and his father is 219,077. This
      corresponds to a probability of paternity of 99.9995% based on a prior
      probability of 50%. Included in this analysis is a linkage analysis of a
      trinucleotide repeat in intron 5 of the AT gene of the various family members,
      which also confirmed maternity and paternity. These studies provide documentation
      of the first spontaneous mutation of an AT gene in a thrombophilic individual,
      resulting in a type I AT deficiency.

PMID- 9929105
TI  - Pulmonary hypertension in patients with myelofibrosis secondary to
      myeloproliferative diseases.
AB  - We examined the clinical characteristics of six patients with myelofibrosis
      secondary to myeloproliferative diseases whose clinical courses were complicated
      by pulmonary hypertension to determine possible causal links between the two
      disorders. Six patients (four male, two female), with diagnoses of
      myeloproliferative disease, myelofibrosis (one with polycythemia vera, three with
      agnogenic myeloid metaplasia, one with unclassified myeloproliferative syndrome,
      one with essential thrombocytosis), and pulmonary hypertension are presented.
      Measurement of the pulmonary artery pressure was performed by Doppler
      echocardiography in all patients and by right sided heart catheterization in four
      patients. The range of resting pulmonary artery systolic pressure was 35 to 47
      mmHg above the mean right atrium by echocardiography. One patient had autopsy
      evidence of pulmonary myeloid metaplasia and interstitial fibrosis; another had
      acute leukemic infiltration of the lung parenchyma. All patients had
      thrombocytosis; symptomatology in one patient with marked thrombocytosis improved
      with plateletpheresis. Two patients suffered systemic thrombosis. All patients
      had severe hepatomegaly. Two patients had evidence of left ventricular
      dysfunction. The interval between the development of dyspnea and death was less
      than seven months in five of the patients. A causal link between pulmonary
      hypertension and myelofibrosis secondary to myeloproliferative diseases is
      suggested for each patient. Hematopoietic infiltration of the pulmonary
      parenchyma, portal hypertension, thrombocytosis, hypercoagulability, and left
      ventricular failure may account in part for the development of pulmonary
      hypertension in these patients. Patients with myelofibrosis and dyspnea should
      have Doppler echocardiography to evaluate pulmonary artery pressures.

PMID- 9929106
TI  - Neonatal hyperbilirubinemia associated with Southeast Asian ovalocytosis.
AB  - We report, herein, an infant who is twin A of a dizygotic twin, with premature
      birth and both twins having hemoglobin (Hb) E heterozygosity. Twin A who had
      Southeast Asian ovalocytosis (SAO) developed neonatal jaundice at the age of 2
      days and needed phototherapy at the age of 3 days. The microbilirubin level was
      rapidly rising up to 535.2 micromol/L (31.3 mg/dl) with the hematocrit value of
      38% at the age of 4 days prior to exchange blood transfusion. Exchange blood
      transfusion was done by 220 ml of O, Rh positive packed red blood cell
      reconstituted with 180 ml of O, Rh positive fresh plasma to lower the bilirubin
      level. Twin A received phototherapy from about 8 hr prior to exchange blood
      transfusion until 3 days later. Twin B, who did not have SAO, developed neonatal
      hyperbilirubinemia and needed only phototherapy. Twin A received a deletion of 27
      basepairs in the erythroid band 3 gene and Hb E heterozygosity from his father.

PMID- 9929107
TI  - Myeloma ascites--a favorable outcome with cyclophosphamide therapy.
AB  - A 71-year-old woman with multiple myeloma (MM) in remission was admitted for
      evaluation of recent abdominal distension and was diagnosed as having massive
      myeloma ascites. The fluid was characterized by a total nucleated cell count of
      6,600/mm3 (67% plasma cells), with a plasma cell CD38+ phenotype. Chemical
      analysis of the fluid showed lactate dehydrogenase of 122 IU/L, total protein of
      2.9 g/dL, albumin of 2.4 g/dL, diastase of 38 IU/dL, cholesterol of 46 mg/dL, and
      C-reactive protein of 3 g/dL. The serum-ascites albumin gradient (SAAG) was low
      (0.9). Electrophoresis of the ascitic fluid showed a monoclonal spike in the
      gamma region and immunoelectrophoresis confirmed the presence of lambda light
      chains similar to those seen in the urine. Further analysis of the ascitic fluid
      showed markedly elevated levels of beta2 microglobulin (11,161 microg/L) and
      interleukin-6 (146 pg/ml compared to serum level of 4.3 pg/ml). There was
      evidence of intraabdominal masses that completely resolved with continuous high
      dose cyclophosphamide (750 mg/m2/day for four days) followed by clinical
      improvement and disappearance of the ascites. We stress the value of complete
      fluid characterization and intensive chemotherapy to achieve a favorable outcome.

PMID- 9929108
TI  - Chronic eosinophilic pneumonia associated with cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphomas (CTCL) are diseases characterized by cutaneous
      infiltrates of malignant clonally expanded T cells. CTCL cells exhibit a cytokine
      profile consistent with T helper-2 type (TH2) cells. Eosinophilic pneumonias are
      individual syndromes characterized by eosinophilic pulmonary infiltrates and
      commonly peripheral blood eosinophilia. CTCL and chronic eosinophilic pneumonia
      are rare clinical entities. We report a patient with the association of CTCL and
      chronic eosinophilic pneumonia. To understand the mechanism leading to the
      eosinophilia, we examined the patient's cytokine profile. This was consistent
      with a high TH2 activity. Her interleukin (IL) 5, 6, and 10 levels were extremely
      high, while her IL-2 and interferon-gamma (IFN-gamma) levels (TH1 profile) were
      low. We believe that eosinophilic pneumonia in this patient is probably secondary
      to high TH2 cytokine levels induced by tumor cells. We suggest that eosinophilic
      pneumonia should be considered as a possible diagnosis in patients with CTCL who
      have respiratory complaints.

PMID- 9929109
TI  - Hydroxyurea use during pregnancy: a case report in sickle cell disease and review
      of the literature.
AB  - A patient being treated for sickle cell disease with hydroxyurea (1 g/d)
      conceived, and drug treatment was discontinued at nine weeks gestational age. The
      pregnancy and delivery were complicated by vaso-occlusive crises. A healthy male
      infant was born at 39 weeks with no evidence of congenital malformations. A
      literature review, including this case, suggests that the risk of hydroxyurea
      exposure during in pregnancy may have been overestimated. Further studies are
      required to determine its safety in pregnancy.

PMID- 9929110
TI  - Idiopathic immune-mediated acquired von Willebrand's disease in a patient with
      angiodysplasia: demonstration of an unusual inhibitor causing a functional defect
      and rapid clearance of von Willebrand factor.
AB  - A case of idiopathic immune-mediated von Willebrand's disease (AvWD) associated
      angiodysplasia and recurrent lower gastrointestinal bleeding is reported.
      Coagulation parameters at presentation were activated partial thromboplastin time
      of 41 sec, bleeding time >15 min, factor VIII procoagulant activity, 5%; von
      Willebrand factor antigen (WF:Ag) 5%, and vWF:ristocetirn cofactor activity 11%
      sodium dodecyl sulfate-agarose gel electrophoresis pattern of plasma vWF showed a
      pattern similar to type II vWD. An in vitro inhibitor against vWF in the
      immunoglobulin (Ig)G fraction of the patient's plasma was demonstrated vWF
      parameters showed a short-lived increase after 1-deamino-8-D-arginine vasopressin
      (DDAVP) administration. The patient's bleeding episodes were initially managed
      adequately with cryoprecipitate replacement therapy and DDAVP, to which she
      became refractory. No significant improvement was achieved following the
      institution of immunosuppressive therapy in the form of high-dose steroids and
      cyclophosphamide. She was then treated with intravenous immunoglobulin (IvIg) to
      which she showed an adequate response in terms of her clinical situation and her
      hemostatic parameters. The patient is on maintenance treatment with repeated
      courses of IvIg based on vWF parameter monitoring. To our knowledge, this is the
      third reported association between idiopathic immune-mediated AvWD and
      angiodysplasia.

PMID- 9929111
TI  - Heterogeneity of clonal development in chronic myeloproliferative disorders.
AB  - Recent reports have suggested a previously unexpected variability in the
      expression of the dominant neoplastic clone in myeloproliferative disorders
      (MPD). We evaluated 49 female patients with MPD and informative at the X-linked
      androgen receptor (AR) locus to establish the X chromosome inactivation pattern
      of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the
      granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity
      of clonal development was found in PMN from patients with other MPD, with up to
      50% of them expressing a polyclonal pattern of X inactivation.

PMID- 9929112
TI  - Quiescent nasal T/NK cell lymphoma manifested as primary central nervous system
      lymphoma.
AB  - A 57-year-old man was diagnosed as primary T/NK-cell central nervous system
      lymphoma (CNSL) with intraocular involvement. However, review of a surgical
      specimen taken three years before for chronic paranasal sinusitis revealed an
      overlooked nasal T/NK cell lymphoma (TNKL), which showed similar histomorphology
      and immunophenotype with the CNS disease. Another patient, a 43-year-old woman,
      was initially diagnosed as a rare primary leptomeningeal T-cell lymphoma with
      ocular manifestation. Three years later, an isolated nasal TNKL emerged.
      Immunohistochemical and cytogenetic studies confirmed the same nature of the CNSL
      and the nasal TNKL. The nasal TNKLs of both patients had a strong expression of
      CD3, CD56, and Epstein-Barr virus antigens, but features of angiodestruction and
      mucosal ulceration were absent. We propose that: 1. a locally silent "quiescent"
      form of nasal TNKL may exist; and 2. a thorough examination and even blind biopsy
      of the nasal cavity is indicated when primary T/NK-cell CNSL is diagnosed.

PMID- 9929114
TI  - Lymphadenopathy associated with monoamine oxidase inhibitors.

PMID- 9929113
TI  - Persistent parvovirus B19 related anemia of seven years' duration in an HIV
      infected patient: complete remission associated with highly active antiretroviral
      therapy.
AB  - A human immunodeficiency virus (HIV)-infected individual was first diagnosed with
      red blood cell aplasia due to B19 parvovirus infection in late 1989. Over the
      subsequent seven-year period, he received a total of 119 units of red blood cells
      (RBCs) and intravenous immunoglobulin every 2-3 weeks. In 1996 combination
      antiretroviral treatment with a protease inhibitor was initiated. He received
      four more units during the following two months and then required no more
      transfusions for the subsequent 24 months of follow-up. His CD4 count
      progressively increased and DNA polymerase chain reaction for parvovirus B19
      became undetectable. Aggressive antiretroviral treatment may effectively diminish
      transfusion requirements among HIV-infected individuals with pure RBC aplasia
      resulting from parvovirus B19 infection.

PMID- 9929115
TI  - Fulminant brain lymphoid infiltration in a patient with chronic lymphocytic
      leukemia.

PMID- 9929116
TI  - Successful treatment for acute lymphoblastic leukemia without blood transfusion
      in a Jehovah's Witness.

PMID- 9929117
TI  - Possible role of soyabean therapy in isolated platelet factor 3 (PF3)
      availability defect.

PMID- 9929118
TI  - Acute promyelocytic leukemia relapse in the central nervous system during
      hematologic and molecular remission.

PMID- 9929119
TI  - Thrombotic thrombocytopenic purpura.

PMID- 9929120
TI  - Nuclear power on-line.

PMID- 9929121
TI  - Chernobyl accident: reconstruction of thyroid dose for inhabitants of the
      Republic of Belarus.
AB  - The Chernobyl accident in April 1986 resulted in widespread contamination of the
      environment with radioactive materials, including (131)I and other radioiodines.
      This environmental contamination led to substantial radiation doses in the
      thyroids of many inhabitants of the Republic of Belarus. The reconstruction of
      thyroid doses received by Belarussians is based primarily on exposure rates
      measured against the neck of more than 200,000 people in the more contaminated
      territories; these measurements were carried out within a few weeks after the
      accident and before the decay of (131)I to negligible levels. Preliminary
      estimates of thyroid dose have been divided into 3 classes: Class 1 ("measured"
      doses), Class 2 (doses "derived by affinity"), and Class 3 ("empirically-derived"
      doses). Class 1 doses are estimated directly from the measured thyroidal (131)I
      content of the person considered, plus information on lifestyle and dietary
      habits. Such estimates are available for about 130,000 individuals from the
      contaminated areas of the Gomel and Mogilev Oblasts and from the city of Minsk.
      Maximum individual doses are estimated to range up to about 60 Gy. For every
      village with a sufficient number of residents with Class 1 doses, individual
      thyroid dose distributions are determined for several age groups and levels of
      milk consumption. These data are used to derive Class 2 thyroid dose estimates
      for unmeasured inhabitants of these villages. For any village where the number of
      residents with Class 1 thyroid doses is small or equal to zero, individual
      thyroid doses of Class 3 are derived from the relationship obtained between the
      mean adult thyroid dose and the deposition density of (131)I or 137Cs in villages
      with Class 2 thyroid doses presenting characteristics similar to those of the
      village considered. In order to improve the reliability of the Class 3 thyroid
      doses, an extensive program of measurement of (129)I in soils is envisaged.

PMID- 9929122
TI  - Biokinetics and dosimetry of titanium tritide particles in the lung.
AB  - Doses of internal radiation from inhalation of metal tritide aerosols are
      potentially a major radiation protection problem encountered by nuclear industry
      workers. Based on results of experiments with rats intratracheally instilled with
      titanium tritide particles and on a self-absorption factor of beta particles
      determined by a numerical method, a biokinetic model was developed for inhaled
      particles of titanium tritide. Results showed that lung burdens of the tritide
      are well represented by a two-component exponential equation; biological half
      lives derived for the retention of 3H in lung were 0.81 d and 66 d. The tritium
      clearance rate via urine or feces was described by bi-phase exponential
      components. At 121 d after instillation, 82% of the initial lung burden of 3H had
      been eliminated, of which 37% was excreted in urine, 29% via feces, and 16%
      through exhaled air. Based on simulation results of the biokinetic model, the
      cumulative absorbed dose and committed effective dose were calculated as well as
      the annual limit of intake (ALI) and derived air concentration (DAC). The ALI and
      DAC values for titanium tritide were a factor of 5 lower than values for
      tritiated water. This information will be useful in developing new guidelines for
      radiation protection purposes.

PMID- 9929123
TI  - Recommended restrictions after 131I therapy: measured doses in family members.
AB  - Absorbed doses to family members of patients treated with (131)I were measured
      using thermoluminescent dosimeters worn on the chest. Twenty-two patients with
      thyroid cancer were hospitalized for 2 d for treatment with 3,700-7,400 MBq, and
      18 hyperthyroid patients were treated on an outpatient basis with 200-600 MBq.
      Doses were measured over periods of 15-21 d following the administration of
      radioiodine in 35 partners and 38 children, aged 4 mo to 25 y. These results were
      correlated with dose rate measurements performed with an ionization chamber, and
      residual thyroid uptake was assessed by scintigraphy over the same period. In the
      cancer group, the residual activity in thyroid remnants was less than 50 MBq in
      all cases at day 4 following treatment and decayed with a mean half-life of 2.2
      (SD: 0.8) d. The dose measured with thermoluminescent dosimeters was lower than
      0.5 mSv in all partners and children. In the hyperthyroid group, the effective
      half-life averaged 6.2 (SD: 1.2) d. The median of the doses measured in partners
      and children were 1.04 mSv (range: 0.05-5.2) and 0.13 mSv (range: 0.04-3.1),
      respectively. Fifteen children (88%) received less than the dose constraint of
      0.5 mSv. The ICRP recommend an annual limit of 1 mSv for the members of the
      public. In addition, dose constraints (for example: 0.5 mSv) should be complied
      with whenever possible. The recommended dose limits are generally well met among
      family members of patients treated with 1311 for cancer. The higher doses
      measured in hyperthyroid patients, compared to thyroid cancer patients, relate to
      a higher (131)I retention by the gland and justify more extended and stringent
      restriction periods, based on residual thyroid activity.

PMID- 9929124
TI  - An EPR dosimetry method for rapid scanning of children following a radiation
      accident using deciduous teeth.
AB  - Electron paramagnetic resonance dosimetry may be applied to whole deciduous teeth
      of children. This makes it feasible to make direct measurement of absorbed gamma
      ray dose in the days and weeks following a nuclear accident, particularly if used
      in conjunction with a public awareness program. The technique reported here
      requires little sample preparation and has resulted in precision of approximately
      30 mGy (1 sigma) for a deciduous incisor. Under conditions for rapid screening
      procedures, the methodology is estimated to provide 0.5 Gy accuracy. The largest
      error in the process is the determination of an appropriate background native
      signal for subtraction from the whole tooth spectrum. The native signal is
      superimposed on the radiation-induced signal, and the subtraction requires
      knowledge of a sample's relative content of enamel and dentin along with their
      relative native signal intensities. Using a composite background standard, an
      equivalent absorbed dose of 70+/-38 mGy (1 sigma) was determined. The lower
      detection limit of the technique was achieved by the elimination of anisotropic
      effects through rotation of the sample during measurement, together with
      subtraction of the standard native background signal and empty tube background
      spectra from the sample spectra.

PMID- 9929126
TI  - Calculation of effective doses for broad parallel photon beams.
AB  - Values of effective dose (E) were calculated for the entire range of incident
      directions of broad parallel photon beams for selected photon energies using the
      Monte Carlo N-Particle (MCNP) transport code with a hermaphroditic phantom. The
      calculated results are presented in terms of conversion coefficients transforming
      air kerma to effective dose. This study also compared the numerical values of E
      and H(E) over the entire range of incident beam directions. E was always less
      than H(E) considering all beam directions and photon energies, but the
      differences were not significant except when a photon beam approaches some
      specific directions (overhead and underfoot). This result suggests that the
      current H(E) values can be directly interpreted as E or, at least, as a
      conservative value of E without knowing the details of irradiation geometries.
      Finally, based on the distributions of H(E) and E over the beam directions, this
      study proposes ideal angular response factors for personal dosimeters that can be
      used to improve the angular response properties of personal dosimeters for off
      normal incident photons.

PMID- 9929125
TI  - Inhaled uranium ore dust and lung cancer risk in rats.
AB  - Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h
      d(-1), 5 days per week for 65 weeks to one of two concentrations of natural
      uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant
      radon content. After inhalation exposure ceased, the rats were allowed to live
      for their natural lifetime. Lung uranium burdens, measured at the time of death
      of each animal, declined exponentially after dust inhalation ceased, and the rate
      of decline was independent of the initial lung burden. Lymph node specific
      burdens ranged from 1 to 60 fold greater than the specific lung burden in the
      same animal. No lymph node tumors were observed. The frequency of primary
      malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung
      tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed
      groups, respectively. There was no difference in tumor latency between the
      groups. Absorbed dose to the lung was calculated for each animal in the study.
      The average doses for all the animals exposed to the low and high dust aerosol
      concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average
      risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both
      groups. The frequency of primary lung tumors was also calculated as a function of
      dose increment for both exposed groups individually and combined. The data
      indicate that, in spite of the above result, lung tumor frequency was not
      directly proportional to dose. However, when malignant lung tumor frequency was
      calculated as a function of dose rate (as measured by the lung burden at the end
      of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting
      dose rate may be a more important determinant of lung cancer risk than dose.
      Conversely, non-malignant lung tumors were significantly correlated with low lung
      burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore
      dust alone in rats creates a risk of primary malignant and non-malignant lung
      tumor formation and that malignant tumor risk was not directly proportional to
      dose, but was directly proportional to dose rate.

PMID- 9929127
TI  - Personal dose equivalent for photons and its variation with dosimeter position.
AB  - This work presents conversion coefficients per air kerma free-in-air for the
      personal dose equivalent, Hp(10), calculated according to its definition by the
      International Commission on Radiation Units and Measurements as a quantity in the
      human body. The values were calculated using Monte Carlo methods for various
      dosimeter positions in the trunk of a voxel model of an adult male, and they are
      given for various directions of incidence of broad parallel photon beams with
      energies between 10 keV and 10 MeV. It is shown that the numerical values of the
      personal dose equivalent depend on the exact position of the dosimeter, with
      maximum differences between 12% and 80%, depending on the beam geometry. It is
      further shown that the recommended calibration quantity Hp slab(10), which has
      been used in ICRP Publication 74 and ICRU Report 57 in the absence of data in the
      human body to approximate personal dose equivalent, does represent the latter
      quantity in a sensible way for some, but not all, beam geometries. Comparison of
      the values for the personal dose equivalent of this work with effective dose
      revealed that Hp(10) is a conservative estimate or close approximation of E for
      most irradiation geometries and photon energies.

PMID- 9929128
TI  - Plutonium contamination in soils in open space and residential areas near Rocky
      Flats, Colorado.
AB  - Spatial analysis of the 240Pu:239Pu isotopic ratio of 42 soil samples collected
      around Rocky Flats Plant near Golden, Colorado, was conducted to assess the
      effect of Rocky Flats Plant activity on the soil environment. Two probability
      maps that quantified the uncertainty of the spatial distribution of plutonium
      isotopic ratios were constructed using the sequential Gaussian simulation
      technique (sGs). Assuming a plutonium isotopic ratio range of 0.152+/-0.003 to
      0.169+/-0.009 is characteristic to global fallout in Colorado, and a mean value
      of 0.155 is representative for the Rocky Flats Plant area, the main findings of
      the current work were (1) the areas northwest and southwest of Rocky Flats Plant
      exhibited a plutonium ratio > or = 0.155, thus were minimally impacted by the
      plant activity; (2) the study area east of Rocky Flats Plant (approximately 120
      km2) exhibited a plutonium isotopic ratio < or = 0.155, which is a definitive
      indicator of Rocky Flats Plant-derived plutonium; and (3) inventory calculations
      across the study area exhibited large standard error of estimates. These errors
      were originated from the high variability in plutonium activity over a small
      sampling scale and the uncertainty in the global fallout isotopic ratio. Using
      the mean simulated estimates of plutonium isotopic ratio, coupled with plutonium
      activity measured at 11 soil pits and additional plutonium information published
      elsewhere, the plutonium loading on the open space and residential areas amounted
      to 111.2 GBq, with a standard error of estimate of 50.8 GBq.

PMID- 9929129
TI  - The relative effectiveness of exposure to 131I at low doses.
AB  - There is much interest in estimating the thyroid cancer risks to children exposed
      to low doses of (131)I from nuclear fallout. Direct epidemiological studies of
      individuals exposed as children to low doses of (131)I have insufficient power to
      yield useful risk estimates. Consequently, extrapolation from risk estimates for
      acute exposure to kilovoltage x rays are used to generate (131)I risk estimates.
      There are two distinct effects that might need to be considered in modifying the
      x-ray generated risk estimates: first, the differing quality of the radiations
      and, second, the lower overall dose rates for (131)I exposure. We suggest that it
      is helpful to split the overall correction factor into its component parts
      radiation quality and radiation dose rate-and consider them separately, in that a
      good deal is known separately about each. There is good radiobiological evidence
      that electrons emitted in (131)I decays are less biologically effective than
      kilovoltage x rays, and the microdosimetric/radiobiological analyses described
      here suggest that the low-dose relative effectiveness is around 0.6 compared to
      kilovoltage x rays. Use of different endpoints suggests that this estimate is
      quite robust, and it agrees well with available animal data. Any correction
      factor for dose-rate effects is likely to be close to unity.

PMID- 9929130
TI  - Neyman-Pearson confidence intervals for extreme low-level, paired counting.
AB  - Neyman-Pearson principles are briefly discussed and 95% confidence intervals of
      the form [0, ##.##] are presented. Use is made of the fact that the probability
      of the difference of two random variables, each with a Poisson distribution, can
      be expressed in terms of modified Bessel functions of integral order and
      elementary functions. The validity of the values is discussed.

PMID- 9929131
TI  - Techniques for measuring radiographic repeat rates.
AB  - Radiographs that must be repeated, which are commonly referred to as "repeats,"
      represent additional, non-billable costs due to increased film, chemistry, and
      equipment use as well as increased personnel time. Furthermore, patients receive
      additional radiation exposure from repeats and must remain on the premises until
      the second exam is completed. Compounding the overt negative financial impact on
      the department is an increased burden on the waiting room and support staff, and
      a decrease in patient throughput. A continuous improvement team was assigned to
      develop an improved technique for monitoring and reducing the number of repeated
      radiographs in a subset of our radiology department. This paper presents a novel
      method of accurately measuring the repeat rate through the use of radiographic
      repeat labels. The labels remove the guesswork from repeat analysis and heighten
      the technologists' awareness of common problems. Additionally, the labels allow
      for detailed analysis of the cause of repeated radiographs, which can provide
      insight for determining remedial actions. Repeat analysis data from our
      institution acquired using the labels before and after implementing remedial
      actions are presented.

PMID- 9929132
TI  - Comment on article by Reichelt et al. Radioactive contamination incidents
      involving protective clothing.

PMID- 9929133
TI  - NEA attacks the millennium bug. Nuclear Energy Agency.

PMID- 9929134
TI  - Hanford radiation dose estimates available to individuals.

PMID- 9929135
TI  - Projected electricity generation costs: 2005-2010.

PMID- 9929136
TI  - Prevention of Obesity. Proceedings of a symposium. Stockholm, Sweden. 26-28
      August, 1998.

PMID- 9929137
TI  - Joint Annual Meeting of The Association for the Study of Food in Society and The
      Agriculture, Food and Human Values Society. San Francisco, California, USA, 4-7
      June, 1998. Abstracts.

PMID- 9929138
TI  - Columbia University Seminar on Appetitive Behavior. Food Intake, Longevity and
      Renal Disease in Genetically Obese Zucker Rats. 11 June 1998.

PMID- 9929139
TI  - Adaptive spatial filtering technique for storage phosphor radiography in portable
      chest radiographs: parameter optimization.
AB  - PURPOSE: To investigate the optimal parameters of adaptive spatial filtering
      (ASF) in storage phosphor radiography for processing portable chest radiographs.
      MATERIALS AND METHODS: Two types of weighting factor curves starting at 383
      digital pixel values (PV) (type B) and at 511 PV (type C) were selected for the
      optimization of ASF. The PV of 27 areas of apparent pulmonary lesions and seven
      retrocardiac areas were measured for original unprocessed and ASF-processed
      images. Three radiologists compared 30 ASF-processed portable chest radiographs
      with apparent pulmonary or pleural lesions with unprocessed images. RESULTS: PV
      measurements revealed no significant change in pulmonary densities in type B, and
      an increase in PV of lower pulmonary densities in type C. Densities of
      retrocardiac areas were more enhanced in type C than in type B. Observer testing
      showed that pulmonary densities were evaluated as unchanged in 90% of type B
      images and 76% of type C images. Changes in mediastinal densities were evaluated
      as adequate in 80% of type B and 90% of type C images. CONCLUSION: The starting
      point of the weighting factor curve of ASF in portable chest radiographs should
      be set the same as in chest radiographs in the upright posteroanterior position
      with high kVp.

PMID- 9929140
TI  - Ultrasonographic screening for arterial occlusive disease in the pelvis and lower
      extremities.
AB  - PURPOSE: To evaluate the accuracy of pulsed Doppler ultrasound (PDUS) and color
      Doppler ultrasound (CDUS) for the screening of arterial occlusive disease in the
      pelvis and lower extremities. METHODS: We studied 52 patients with intermittent
      claudication or lower extremity "coolness." Pulsed Doppler waveforms were
      measured in the inguinal and popliteal regions and were classified according to
      their pattern. Patients with abnormal waveforms underwent subsequent CDUS
      evaluation from the aortic bifurcation to the popliteal arteries. All patients
      also underwent conventional angiography. RESULTS: All stenoses (> 50%) and
      occlusions on angiography were detected by PDUS. The combination of PDUS and CDUS
      allowed detection of 78.0% of stenotic lesions (> 50% narrowing) and 96.6% of
      occlusive lesions in the iliofemoral regions and in 100% of stenotic lesions (>
      50% narrowing) and occlusive lesions in the femoropopliteal regions. PDUS
      required approximately 3 min. About more 5 min are required when CDUS was added.
      CONCLUSION: Combined PDUS and CDUS appears to be a rapid, highly sensitive means
      of screening for arterial occlusive disease in the pelvis and lower extremities.

PMID- 9929141
TI  - Bone scan appearance of renal osteodystrophy in diabetic chronic renal failure
      patients.
AB  - To investigate Tc-99m methylenediphosphonate (MDP) bone scan appearance in
      diabetic chronic renal failure patients, we compared the bone scan images of
      chronic renal failure patients with and without diabetes. The number of patients
      studied was 134, of whom 43 had diabetes. Two nuclear medicine physicians read Tc
      99m MDP bone scan images and for six areas - the axial skeleton, long bone, skull
      and mandible, periarticular areas, costochondral junction, and sternum - assigned
      a score of either 1 or 0. The sums of scores were compared. We also performed
      multivariate analysis including sex, age, and serum creatinine level using
      analysis of covariance. DM group patients scored significantly lower (2.01+/
      0.95) than those of the non-DM group (3.26+/-1.16). Analysis of covariance
      revealed that the lower DM group score was independent of sex, age, and serum
      creatinine level. The bone scans of diabetic chronic renal failure patients
      showed less Tc-99m MDP uptake than those of non-diabetic patients. Thus,
      diagnosing renal osteodystrophy in diabetic chronic renal failure patients on
      bone scan images could be difficult.

PMID- 9929142
TI  - Lower leg ischemia associated with aortic dissection.
AB  - Lower leg ischemia associated with aortic dissection is a potentially life
      threatening condition requiring immediate treatment. To better understand the
      diagnostic factors and improve the treatment strategy of this serious
      complication, we analyzed our experience regarding the radiographic findings,
      treatment, and outcome in eight patients (aged 28-72 years, six men and two
      women). CT revealed type A aortic dissection in seven patients and type B in one.
      The obstructed site was in the iliac artery in five patients and in the abdominal
      aorta below the renal arteries in three. Surgical procedures included five
      ascending aortic graft replacements, three femoro-femoral bypasses, and one each
      of surgical fenestration, aorto-iliac bypass, and axillo-femoral bypass with
      thrombectomy. Endovascular treatment was performed in two patients, iliac stent
      placement in one, and thrombolysis of the iliac artery in one. Five patients
      survived and three died due to myonephrotic metabolic syndrome in two and
      postoperative bleeding in one. Treatment strategy depends on several issues
      regarding aortic dissection including ascending aortic involvement, patent false
      lumen, entry site, renal artery involvement, and thrombosis in a true or false
      lumen. CT and angiography are the most important methods for deciding upon
      appropriate therapy in each individual.

PMID- 9929143
TI  - Radiographic imaging of Pneumocystis carinii pneumonia in patients with acquired
      immunodeficiency syndrome.
AB  - We reviewed the radiographic imaging of Pneumocystis carinii pneumonia in
      patients with acquired immunodeficiency syndrome to determine the findings of
      chest radiography, computed tomography, and gallium scintigraphy and to analyze
      the time course of the resolution of abnormalities on chest radiographs after the
      initiation of therapy. The patients were one woman and 43 men (mean age, 38
      years). After initiation of therapy, the chest radiograph demonstrated
      deterioration in 36% of patients, rapid improvement in 51%, and no change for the
      first two weeks in 13%. In 80% of patients, chest radiographs showed improvement
      within three weeks. On average, the radiographic abnormalities resolved in 45
      days. We conclude that chest radiographic abnormalities may appear to have
      worsened after the initiation of therapy, but most of the follow-up films
      eventually show improvement.

PMID- 9929144
TI  - Enhancement of cisplatin sensitivity of quiescent cells in solid tumors by
      combined treatment with tirapazamine and low-temperature hyperthermia.
AB  - We examined the enhanced chemosensitivity of quiescent (Q) cells in solid tumors
      to cis-diamminedichloroplatinum (II) (cisplatin) by combined treatment with
      tirapazamine (TPZ) and mild heating. C3H/He and Balb/c mice bearing SCC VII and
      EMT6/KU tumors, respectively, received continuous administration of 5-bromo-2'
      deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all
      proliferating (P) cells. TPZ was administered intraperitoneally 2 h before
      cisplatin injection and/or tumors were locally heated at 40 degrees C for 60 min
      immediately after cisplatin injection. Sixty minutes after cisplatin injection,
      the tumors were excised, minced and trypsinized. The tumor cell suspensions were
      incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN)
      frequency in cells without BrdU labeling (= Q cells) was determined using
      immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells
      was determined from the tumors that were not pretreated with BrdU. The
      sensitivity to cisplatin was evaluated in terms of the frequency of induced
      micronuclei in binuclear tumor cells (MN frequency). Other groups of tumor
      bearing C3H/He and Balb/c mice not given BrdU were injected with 195mPt
      radiolabeled cisplatin. In both tumor systems, the MN frequency in Q cells was
      lower than that in the total cells. TPZ and mild heat treatment elevated the MN
      frequency in total and Q cells in both tumor systems, and to a higher extent in Q
      cells. The combination of TPZ and mild heat treatment increased the MN frequency
      more markedly than treatment with either TPZ or mild heating alone. In total
      tumor cells, TPZ and mild heat treatment increased the MN frequency in EMT6/KU
      tumor cells more markedly than in SCC VII tumor cells. 195mPt-labeled cisplatin
      uptake into total tumor cells was increased by mild heat treatment but not by
      TPZ. The cisplatin-sensitivity of Q cells was lower than that of total cells in
      both tumor systems. TPZ was thought to sensitize Q cells by killing the hypoxic
      cells without influencing tumor blood flow, and mild hyperthermia appeared to
      sensitize Q cells by distributing more cisplatin with an increase in blood flow
      in solid tumors.

PMID- 9929146
TI  - Effects of right hemithoracic irradiation on ceftazidime penetration into the
      alveolar space in rats.
AB  - The effect of thoracic irradiation on antibiotic penetration into the alveolar
      space was determined in a hemithoracic irradiation rat model to evaluate
      radiation-induced acute alveolar injury at various time intervals. The results of
      this investigation may be summarized as follows: (1) The transfer of ceftazidime
      (CAZ: Modacin) from blood to lung tissue, that is, the permeability of pulmonary
      capillary epithelium, and the transfer of ceftazidime from lung tissue to
      bronchoalveolar lavage fluid, that is, the permeability of the alveolar
      epithelium, peaked at 4 to 5 weeks after thoracic irradiation; (2) the time
      course of change in the absolute concentration of ceftazidime in lung tissue
      showed a significant increase not only in the irradiated lung but also in the
      contralateral non-irradiated lung 3 days or more after irradiation. The finding
      that the administration of antibiotics may cause a significant increase in drug
      concentration in lung tissue even in the contralateral lung at 3 days after
      irradiation suggests that the change induced at the alveolar level immediately
      after irradiation affects the non-irradiated lung field through an as yet unknown
      mechanism.

PMID- 9929145
TI  - Consistency of variables in PCS and JASTRO great area database.
AB  - PURPOSE: To examine whether the Patterns of Care Study (PCS) reflects the data
      for the major areas in Japan, the consistency of variables in the PCS and in the
      major area database of the Japanese Society for Therapeutic Radiology and
      Oncology (JASTRO) were compared. METHODS AND PATIENTS: Patients with esophageal
      or uterine cervical cancer were sampled from the PCS and JASTRO databases. From
      the JASTRO database, 147 patients with esophageal cancer and 95 patients with
      uterine cervical cancer were selected according to the eligibility criteria for
      the PCS. From the PCS, 455 esophageal and 432 uterine cervical cancer patients
      were surveyed. Six items for esophageal cancer and five items for uterine
      cervical cancer were selected for a comparative analysis of PCS and JASTRO
      databases. RESULTS: Esophageal cancer: Age (p=.0777), combination of radiation
      and surgery (p=.2136), and energy of the external beam (p=.6400) were consistent
      for PCS and JASTRO. However, the dose of the external beam for the non-surgery
      group showed inconsistency (p=.0467). Uterine cervical cancer: Age (p=.6301) and
      clinical stage (p=.8555) were consistent for the two sets of data. However, the
      energy of the external beam (p<.0001), dose rate of brachytherapy (p<.0001), and
      brachytherapy utilization by clinical stage (p<.0001) showed inconsistencies.
      CONCLUSION: It appears possible that the JASTRO major area database could not
      account for all patients' backgrounds and factors and that both surveys might
      have an imbalance in the stratification of institutions including differences in
      equipment and staffing patterns.

PMID- 9929147
TI  - Prognostic factors for patients with esophageal cancer treated with radiation
      therapy in PCS: a preliminary study.
AB  - PURPOSE: We investigated the prognostic factors, with special reference to age,
      for esophageal cancer patients, who did not receive surgery but were treated with
      radiation in the context of a Patterns of Care Study (PCS) in Japan. PATIENTS AND
      METHODS: The fifth PCS database format employed in the United States was used to
      collect information on 455 esophageal cancer patients by external audit. The data
      of patients who had not received surgery (n=252) were further selected and
      divided into two age groups, patients 75 years old or older (n=90) and patients
      younger than 75 years (n=162). Cox's proportional hazards model was used for the
      statistical analysis, with crude survival as the endpoint. Variables tested were
      age; Karnofsky performance status (KPS); history of pulmonary disease,
      cardiovascular disease, and diabetes; AJCC stage; external dose; treatment
      period; combination with chemotherapy; utilization of brachytherapy, and
      stratification of institutions. RESULTS: Statistically significant prognostic
      factors for all patients in the non-surgery group were KPS p=.0001), stage
      (p=.0001), and utilization of brachytherapy (p=.0102). For younger patients, KPS
      (p=.0001), stage (p=.0007), external dose (p=.0001), and utilization of
      brachytherapy (p=.0034) were significant, and for the elderly, stage (p=.0001)
      and external dose (p=.0006). CONCLUSION: Although this was a preliminary study,
      age was not a significant prognostic factor for esophageal cancer patients in the
      non-surgery group, and making the external dose more than 60 Gy appears to be
      effective for improving survival of elderly as well as younger patients.

PMID- 9929148
TI  - Enhanced regeneration response of laryngeal and hypopharyngeal mucosa with
      accelerated hyperfractionated radiation therapy for glottic cancers.
AB  - The course and severity of acute mucosal reactions in 22 patients with previously
      untreated T1-2N0 glottic cancers were compared between two treatment schedules
      with different dose intensities: accelerated hyperfractionated radiation therapy
      (AHF) and standard conventional fractionation radiation therapy (CF). AHF
      consisted of a twice-daily fractionation of 1.5 Gy 10 times weekly to a total
      dose of 66 Gy given in 30-40 (median, 33) days. For CF, the fractionation was 2
      Gy five times weekly for a total dose of 66 Gy in 45-51 (median, 49) days. Both
      treatment schedules were well tolerated and no treatment interruptions were
      necessary. The mucosal reaction reached a peak score clearly earlier with AHF
      than CF and already demonstrated improvement in the final treatment week. In
      contrast, the reaction persisted with CF. It is suggested that damaged mucosal
      tissues with AHF can be effectively compensated by enhanced regeneration response
      due to an adequately high dose intensity, suggesting a possible tolerability
      advantage for AHF.

PMID- 9929149
TI  - Gamna-gandy bodies of the spleen depicted by unenhanced CT: report of two cases.
AB  - We report two cases of Gamna-Gandy bodies (GGB) of the spleen, confirmed by MRI,
      in which unenhanced CT depicted multiple faint high-attenuation spots in the
      spleens. These spots were considered to represent the calcifications in GGB. CT
      and MRI reflect the different compositions of GGB. In a very limited number of
      patients with portal hypertension, unenhanced CT may detect GGB, and this entity
      should be included in the differential diagnosis of calcified foci of the spleen.

PMID- 9929150
TI  - Reversible symptomatic venous congestion after treatment of dural arteriovenous
      fistula using NBCA.
AB  - We treated a 73-year-old man with a dural arteriovenous fistula (AVF) with
      cortical venous drainage of the left mastoid region using transarterial
      embolization of the middle meningeal and occipital arteries with n-butyl 2
      cyanoacrylate (NBCA). The patient's clinical symptoms improved dramatically.
      Three months after the procedure, follow-up CT showed resolution of white matter
      edema and follow-up angiograms showed no evidence of a recurrent AVF. This report
      indicates that dural AVFs without sinus drainage can be cured solely with
      transarterial NBCA embolization.

PMID- 9929151
TI  - Meningioma associated with acute subdural hematoma--case report.
AB  - A 48-year-old woman presented with sudden left hemiplegia with headache, which
      deteriorated two days later. CT scan showed repeated intratumoral and subdural
      hemorrhages. Magnetic resonance imaging showed a parasagittal tumor infiltrating
      into the superior sagittal sinus, with intratumoral hemorrhage and acute subdural
      hematoma in the interhemispheric fissure. The intratumoral hematoma had several
      different intensities, which indicated repeated hemorrhages. The subdural
      hematoma and the tumor were removed via frontoparietal craniotomy. The
      histological diagnosis was fibrous-type meningioma with a high Ki-67 labeling
      index (6.7). As there were tumor cells within the subdural hematoma, it seemed to
      have resulted from tumoral hemorrhage. A high index of cell proliferation may
      indicate some mechanism responsible for hemorrhage in malignant tumor.

PMID- 9929152
TI  - MRI appearance of ruptured corpus luteum.
AB  - A 20-year-old woman was admitted complaining of lower abdominal pain.
      Transabdominal ultrasound revealed a fluid collection in the pouch of Douglas and
      an irregularly shaped ovary with cystic lesions. Malignant cystic mass of the
      right ovary was highly suspected from the ultrasound findings. Transvaginal
      peritoneal centesis yielded a bloody fluid, but the pregnancy test was negative.
      On the third day of admission, menstruation began. MR examination performed four
      days after the initial onset of pain showed a subacute hematoma just adjacent to
      the right ovary, and segmental interruption of the right ovarian cortex. Based on
      these MR findings and the patient's history, subacute hemorrhage from the right
      ovarian corpus luteum was suspected, and this was confirmed with surgical
      exploration.

PMID- 9929153
TI  - Radiation therapy for cancer in elderly patients over 80 years of age.
AB  - The elderly population has recently increased, and the need for cancer care and
      treatment for the elderly is likely to grow. We report on radiation therapy for
      cancer in elderly patients over 80 years of age. During the period from 1985 to
      1996, 90 elderly patients (54 men, 36 women) aged over 80 years were treated with
      radiation therapy. Many patients had primary tumors of the esophagus, head and
      neck, and lungs, in that order of frequency. Fifty-seven percent of the patients
      were treated with radical radiotherapy, and 70% were treated with radiotherapy
      alone. The rate of completion of radiation therapy was 90%, and the response rate
      was 82%. Radiation therapy played an important role in the treatment of the
      patients over 80 years of age. The half of our patients had concurrent medical
      problems, and were dependent on their home physicians both before and after
      radiation therapy. We consider that radiation oncologists should make an effort
      to form a good relationship with home physicians.

PMID- 9929154
TI  - Effects of trans-retinoic acid, 9-cis-retinoic acid, 1alpha,25-(dihydroxy)vitamin
      D3 and a novel apoptosis-inducing retinoid on breast cancer and endothelial cell
      growth.
AB  - Breast cancer cell growth inhibition was not synergistically enhanced by trans
      retinoic acid (RA) or 9-cis-RA plus 1alpha,25-(dihydroxy)vitamin D3 (DHVD). The
      retinoid/DHVD combinations did lower their 50% effective concentrations for
      inhibiting retinoid-sensitive MCF-7, but not retinoid-refractory BT-20, breast
      cancer cell growth. In contrast, the synthetic retinoid 6-[3-(1-adamantyl)-4
      hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) and its analog SR11389
      inhibited the growth of both cell lines. Unlike RA, 9-cis-RA and DHVD, AHPN and
      SR11389 also potently inhibited human umbilical vascular endothelial cell growth.
      These results on AHPN and SR11389 suggest that angiogenesis of tumor
      microvasculature should also be an effective therapeutic target for this new
      compound class.

PMID- 9929155
TI  - Evaluation of radiation-induced DNA damage and DNA repair in human lung cancer
      cell lines with different radiosensitivity using alkaline and neutral single cell
      gel electrophoresis.
AB  - Using the comet assay, radiation-induced DNA strand breaks were evaluated in
      human lung cancer cell lines with different radiosensitivity (U-1285, U-1906E, U
      1752 and U-1810). Single strand breaks were more sensitive indicators of the
      radiation-induced damage than double strand breaks. However, there was no
      consistent pattern in the way the various cell lines responded to 1-5 Gy of gamma
      irradiation and all cell lines showed a remarkably efficient DNA repair after 1
      h. In a separate study of the repair kinetics of DNA double strand breaks, the
      radioresistant cell line U-1810 showed a more efficient initial strand rejoining
      than the radiosensitive cell line U-1285 after irradiation at 2 Gy. The latter
      finding suggests that the detection of early DNA repair may be useful when
      monitoring the intrinsic radiosensitivity of human lung cancer cells.

PMID- 9929156
TI  - Enhancing effects of green tea components on the antitumor activity of adriamycin
      against M5076 ovarian sarcoma.
AB  - We have investigated the combined treatment of components of green tea with
      adriamycin against M5076 ovarian sarcoma, which exhibits low sensitivity to
      adriamycin. In M5076 tumor-bearing mice, the injection of adriamycin alone did
      not inhibit tumor growth, whereas the combination of theanine and adriamycin
      significantly reduced the tumor weight to 62% of the control level. When combined
      with theanine, effective antitumor activity of adriamycin was observed without an
      increase in the dosage. Theanine specifically increased the adriamycin
      concentration in the tumor by 2.7-fold. In contrast, theanine decreased the
      adriamycin concentrations in normal tissues. On the other hand, in vitro
      experiments proved that theanine inhibited the efflux of adriamycin from tumor
      cells, suggesting a theanine-induced increase in the adriamycin concentration in
      such tumors in vivo. Furthermore, the oral administration of theanine or green
      tea similarly enhanced the antitumor activity of adriamycin. In conclusion, the
      combination of theanine with adriamycin showed antitumor efficacy in spite of the
      non-effective dose of adriamycin on M5076 ovarian sarcoma. We have found that the
      modulating action of theanine is useful in clinical cancer chemotherapy.

PMID- 9929157
TI  - Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate
      cancer cells.
AB  - We investigated the effect of various neuropeptides present in the prostate,
      including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide
      (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide
      (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid
      hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells
      through a reconstituted basement membrane (Matrigel) using a Transwell cell
      culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor
      cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon
      and PTH-rP had no significant effect. Both CGRP and GRP also increased the
      haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These
      three neuropeptides had no effect on either adhesion to fibronectin and laminin
      or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they
      affect the growth of tumor cells at concentrations used in this study. These
      results indicate that both GRP and CGRP increased the invasive potential of PC-3
      cells probably through enhancement of cell motility, while SP inhibited the
      invasiveness through suppression of motile response.

PMID- 9929158
TI  - Induction of cyclin-dependent kinase inhibitor p21 in vesnarinone-induced
      differentiation of squamous cell carcinoma cells.
AB  - Induction of differentiation is today a useful strategy in cancer therapy but the
      clinical practice is insufficient in squamous cell carcinomas. We examined the
      effect of vesnarinone, a differentiation-inducing agent, on the cell cycle and
      cellular differentiation in four cell lines established from oral squamous cell
      carcinomas possessing a wild-type or mutated p53. Vesnarinone dose-dependently
      inhibited cell growth and induced G1 phase accumulation regardless of p53 gene
      mutation. The expression of involucrin and transglutaminase was increased by 4
      days treatment with 60 microg/ml vesnarinone in all cell lines. Although p21
      promoter activity was suppressed by vesnarinone, p21-mRNA was stabilized by the
      agent and expression of p21-mRNA was maintained for a long time. Corresponding to
      the prolonged p21-mRNA expression, p21 protein was induced by cell treatment with
      60 microg/ml vesnarinone for 12 h and longer. The induced p21 protein bound
      cyclin E and suppressed cyclin E/Cdk2 kinase activity suppressing the
      phosphorylation of retinoblastoma (Rb) protein. These results suggest that
      vesnarinone possesses activity to induce p21 protein by stabilizing its mRNA with
      induction of differentiation of squamous cell carcinoma cells in a p53
      independent manner.

PMID- 9929159
TI  - Estrogens and polyamines in breast cancer: their profiles and values in disease
      staging.
AB  - The urinary concentrations of 16 estrogens and 11 polyamines were quantitatively
      determined by gas chromatography-mass spectrometry and gas chromatography with
      nitrogen-phosphorus detection. Samples from patients with stages I-IV of breast
      cancer (35 cases, aged 27-65 years) as well as from age-matched normal female
      subjects (25 cases, aged 22-61 years) were tested. Also, the ratios of precursor
      to product metabolite including 16alpha-OH E1 to 2-OH E1, which are linked to
      estrogen and polyamine biosynthetic pathways, were determined to explore enzyme
      involvement in breast cancer and to evaluate the potential usefulness of these
      ratios and concentrations as disease staging markers. It was confirmed that major
      estrogens and 16a-OH E1 were positively associated with breast cancer and
      catechol estrogens including 2-OH E1 were inversely associated with breast
      cancer. The ratios of N1-acSp/Spd and 16alpha-OH E1/2-OH E1 might be a useful
      dual marker for staging of breast cancer. From the variation of the relative
      ratios of polyamines, it is suggested that alteration in polyamine oxidase (PAO)
      activity may play an important role in the development of breast cancer.

PMID- 9929160
TI  - Cloning of the rat proto-oncogene bmi-1.
AB  - The bmi-1 gene was identified as a common proviral integration site in Moloney
      murine leukemia virus. In the present studies, we cloned and sequenced the rat
      bmi-1 gene by reverse transcriptase-polymerase chain reaction (RT-PCR) using
      degenerate PCR primers of homologous sequences between mouse and human. We found
      93% identity to the mouse bmi-1 cDNA and 90% identity to the human bmi-1. The
      open reading frame encodes a protein of 324 amino acids. In the deduced amino
      acid sequence we observed 95% and 94% homology to the mouse and human,
      respectively. The structural motifs, a novel zinc finger motif and a putative
      helix-turn-helix motif, were conserved in the predicted rat BMI-1 protein. We
      also confirmed ubiquitous expression of bmi-1 in normal tissues except brain.
      These results suggest functional conservation of the bmi-1 gene in the rat.

PMID- 9929161
TI  - bcl-2 protein expression in endometrial carcinoma: the lack of correlation with
      p53.
AB  - bcl-2 expression was examined on paraffin-embedded specimens in proliferative,
      hyperplastic, and neoplastic human endometrium by immunohistochemistry. The
      results of bcl-2 immunostaining in endometrial carcinomas were compared with
      clinicopathological indicators as well as with p53 accumulation. The streptavidin
      peroxidase detection system was used and the intensity and the distribution of
      immunostaining was evaluated semiquantitatively by counting H-score values.
      Expression of the bcl-2 protein was found in 2 out of 5 cases of proliferative
      endometrium (mean H-score 0.4, range 0.35-0.45), 4 out of 5 cases of simple
      hyperplasia (mean H-score 1.23; range 1.0-1.4), 4 out of 5 cases of complex
      hyperplasia (mean H-score 1.1; range 0.7-1.2) and in 7 out of 25 cases of
      endometrial carcinoma (mean H-score 0.48; range 0.35-0.65). All bcl-2 positive
      slides were obtained from patients who had endometrial cancer and who were in the
      early (stage I due to FIGO) clinical stage of the disease. bcl-2 expression was
      not related to age, surgical stage or histopathological features, and neither was
      there an inverse correlation between bcl-2 immunostaining and p53 expression
      reported in the study of neoplastic endometrium. Our data indicate that
      mechanisms other than p53 may play a role in the regulation of bcl-2 expression
      in endometrial carcinomas.

PMID- 9929162
TI  - Antitumor activities of vanadium(IV), manganese(IV), iron(III), cobalt(II) and
      copper(II) complexes of 2-methylaminopyridine.
AB  - The effect of Cu(II), Mn(IV), Fe(III), V(IV) and Co(II) complexes of 2
      methylaminopyridine (L) having superoxide dismutase (SOD)-like activities on
      Ehrlich ascites carcinoma (EAC) cells was studied. Each of these complexes was
      intraperitoneally administered (10 mg/kg body weight for 9 days) to Swiss albino
      mice implanted intraperitoneally with 1 x 10(6) EAC cells. Six days after the
      last treatment the EAC cells were harvested using a heparinized syringe. The
      volume of EAC cells and EAC cell viability as well as changes in the levels of
      tumor cell enzyme activities of SOD, catalase, glutathione peroxidase (GSH-Px),
      glutathione reductase (GSH-R) and glucose-6-phosphate dehydrogenase (G6PD) were
      tested to examine the antitumor effects of these complexes. Both tumor volume and
      tumor cell viability were significantly lowered in complex-treated mice. After
      tumor transplantation and treatment with the complexes, the activities of GSH-Px
      and GSH-R were significantly lowered while SOD and G6PD activities were increased
      in EAC cells compared to their levels in EAC cells harvested from saline-treated
      mice.

PMID- 9929163
TI  - Apoptosis is induced in aging SV40 T antigen-transformed human fibroblasts
      through p53- and p21CIP1/WAF1-independent pathways.
AB  - When comparing SV40 T antigen-transformed human fibroblasts of a younger
      generation (24 population doubling) and aging stage (58 population doubling), we
      found that detachment of cells from the culture surface occurred more frequently
      in aging cells. DNA fragmentation and chromatin condensation which are typical
      findings of apoptosis occurred more frequently in aging cells as compared to
      cells of a younger generation. There is no increase in the p53 level or decrease
      in the SV40 T antigen level in aging cells as compared to cells of a younger
      generation. Retinoic acid treatment which can effectively suppress p21 gene
      expression did not prevent apoptosis. These findings indicate that apoptosis that
      occurs due to aging-transformed human fibroblasts is mediated through p53- and
      p21-independent pathways.

PMID- 9929164
TI  - Different cytokines modulate ubiquitin gene expression in rat skeletal muscle.
AB  - Intravenous administration of different cytokines caused important changes in the
      expression of ubiquitin genes in skeletal muscle. Tumour necrosis factor-alpha
      caused a 2.2- and 1.9-fold increase in the expression of the 2.4 and 1.2 kb
      transcripts, respectively. Administration of interferon-gamma also caused a 2.2-
      and 1.8-fold increase in the 2.4 and 1.2 kb transcripts, respectively. While
      administration of leukaemia inhibitory factor and interleukin-6 resulted in no
      changes in ubiquitin gene expression, interleukin-1 administration also caused an
      increase in both ubiquitin gene transcripts (2.8- and 1.9-fold for the 2.4 and
      1.2 kb transcripts, respectively). The results suggest that some of the cytokine
      effects on the ubiquitin system gene expression could be related to the enhanced
      skeletal muscle proteolysis found during cancer cachexia and other pathological
      states.

PMID- 9929165
TI  - p53 inactivating mutations in Chinese nasopharyngeal carcinomas.
AB  - Previously a low frequency of p53 mutations was detected in nasopharyngeal
      carcinoma (NPC) using molecular techniques to screen for mutations, yet
      immunohistochemical staining revealed a high frequency of p53 aberrant proteins.
      These findings might be attributed to the occurrence of p53 mutations outside the
      common hot spots and/or the inactivation of the protein through interactions with
      cellular or viral proteins. Using a previously established simple and sensitive
      p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for
      p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and
      in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases.
      Two p53 mutations were detected in exon 7 and two were detected in exon 8.
      Interestingly, the exon 8 mutations observed in NPC lie in codons which appear to
      be hot spots for mutations in other head and neck cancers.

PMID- 9929166
TI  - Early differential expression of two glutaminase mRNAs in mouse spleen after
      tumor implantation.
AB  - The influence of progressive tumor growth on phosphate-activated glutaminase
      (PAG) expression in splenocytes from mice bearing Ehrlich ascites carcinoma cells
      was investigated. Implantation of Ehrlich ascites tumor cells in the peritoneal
      cavity of mice led to a 2.3-fold stimulation of spleen PAG activity 48 h later.
      Four days after tumor implantation the glutaminase activity had returned to
      nearly basal value and remained at this level throughout the tumor development.
      Northern blot analysis indicated that two species of glutaminase mRNA were
      expressed in the spleen, which showed a differential expression pattern during
      the first 2 days after tumor implantation. The abundance of the transcript of
      higher electrophoretic mobility (approximately 3 kb) constantly increased over
      the first 2 days of tumor growth. The mRNA of lower electrophoretic mobility
      (approximately 6 kb) peaked at 12 h after tumor implantation and returned to
      control values at 48 h. These results demonstrate that tumor has the capability
      of altering glutaminase expression in the host spleen.

PMID- 9929167
TI  - Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids.
AB  - A method for estimating in the same assay both aromatase and 17beta
      hydroxysteroid dehydrogenase activities in human placental microsomes using
      radiolabelled [1,2,6,7-3H]4-androstene-3,17-dione was proposed. In this assay,
      estrone (E1) and estradiol (E2) produced were separated by HPLC and estimated
      using a radioactive flow detector. Using this method, the inhibitory effect of
      various flavonoids, including flavone, flavanone and isoflavone, on the human
      placental aromatase and 17beta-hydroxysteroid dehydrogenase was studied.
      Flavonoids were shown to be potent inhibitors of both aromatase and 17beta
      hydroxysteroid dehydrogenase activities. We found that 7-hydroxyflavone and
      apigenin are the most effective aromatase and 17beta-hydroxysteroid dehydrogenase
      inhibitors, respectively. Experiments showed that a hydroxyl group in position 7
      was essential for anti-17beta-hydroxysteroid dehydrogenase activity. However,
      flavonoids with 7-methoxy or 8-hydroxyl groups on the A ring showed only anti
      aromatase activity. Structure-activity relationships were discussed.

PMID- 9929168
TI  - Characterization of muscarinic receptors in the human melanoma cell line SK-Mel
      28 via calcium mobilization.
AB  - In melanoma cells of primary and metastatic human melanomas muscarinic
      cholinergic receptors are present. Muscarinic receptors were shown to be
      expressed in morphogenetically active embryonic cells. Therefore, the possibility
      exists that in melanomas an embryonic trait is re-expressed after transformation.
      In the present study, we demonstrated the presence of muscarinic receptors in the
      human melanoma cell line SK-Mel-28 by immunofluorescence with the monoclonal
      antibody M 35 and characterized the receptors further by measuring calcium
      mobilization after muscarinic stimulation. Cell suspensions were stained with
      fura-2 and fluorescence was followed at 380 nm excitation in a fluorimeter
      cuvette. After the addition of acetylcholine or carbachol a steep decrease in
      fluorescence intensity indicated calcium mobilization from intracellular stores
      (peak reaction), which was followed by a constantly lowered fluorescence level
      indicating a steady influx of extracellular calcium in the presence of agonist.
      By quantitative evaluation, dose-response curves were obtained from which an ED
      of 4.3 x 10(-6) M was calculated for acetylcholine and an ED of 2.2 x 10(-5) M
      was calculated for carbachol. After preincubation with antagonists the dose
      response curve of acetylcholine was shifted to the right. The inhibition constant
      of pirenzepine was calculated as 3.9 x 10(-7) M, of methoctramine as 6.8 x 10(-7)
      M and of 4-DAMP-mustard as 1.9 X 10(-8) M. Comparison with the data from the
      literature and those obtained in the chick embryo indicates that the muscarinic
      receptor in SK-Mel-28 melanoma cells pharmacologically behaves as the M3 type and
      corresponds to the embryonic muscarinic receptor characterized by us in earlier
      studies.

PMID- 9929169
TI  - Activation of heterocyclic amines by combinations of prostaglandin H synthase-1
      and -2 with N-acetyltransferase 1 and 2.
AB  - Cooking of meats produces several heterocyclic amines which are mutagenic and
      potentially carcinogenic. We found that metabolic activation of one of these
      heterocyclic amines, the quinoline derivative 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), can be catalyzed by prostaglandin H synthase (PHS) as well as
      by CYP1A2. N-Acetyltransferase (NAT) increased IQ-DNA adduct formation by either
      of these pathways. In sonicate from transiently transfected COS cells, NAT1
      increased CYP1A2 catalyzed adduct formation 4-fold while NAT2 increased adduct
      formation 12-fold. Both expressed human and purified ovine PHS-1 and PHS-2
      catalyzed IQ-DNA adduct formation. The presence of NAT1 and NAT2 increased PHS-1
      catalyzed adduct formation 2.5- and 4-fold, respectively. PHS-2 catalyzed IQ
      adduct formation was also enhanced by either NAT. The pyridine derivative, 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, also produced by protein
      pyrolysis, did not form detectable DNA adducts during incubation with PHS. These
      results indicate that IQ is a substrate for both PHS-1 and PHS-2 and that NAT
      increases the ability of the resulting IQ metabolites to cause DNA damage. PHS
      activity, constitutive and induced, as well as NAT polymorphisms should be
      considered as factors in environmental carcinogenesis.

PMID- 9929170
TI  - A simulation test of hominoid species number at Lufeng, China: implications for
      the use of the coefficient of variation in paleotaxonomy.
AB  - High dental metric variation in the large hominoid sample from the late Miocene
      site of Lufeng, China has been interpreted in two ways: (1) there are two
      morphologically similar species that broadly overlap in size, and (2) there is
      one species that is more highly sexually dimorphic in dental size, and perhaps in
      body size, than any extant primate. It has been claimed that the high levels of
      dental metric variation falsify the single-species hypothesis, which has been
      viewed implicitly as corroboration of the two-species hypothesis. However, the
      two-species hypothesis has not been subjected to testing. Here we test the two
      species hypothesis using computer simulations to attempt to reproduce the unusual
      pattern of intrasexual and intersexual dental metric variation observed in the
      Lufeng postcanine dentition. Conditions of the simulation experiments were
      optimized to favor the two-species hypothesis. It was found that, although the
      Lufeng pattern of metric variation could be reproduced by sampling two species,
      the likelihood of this occurrence was very low even when the conditions were
      optimized to the point of improbability. We conclude that the likelihood is very
      high that the Lufeng sample is composed of one species that is more highly
      sexually dimorphic in the postcanine dentition than any extent primate species.
      If so, then the high levels of sexual dimorphism and intraspecific dental metric
      variation in this species violate the central assumption of methods that employ
      the coefficient of variation (CV) for paleotaxonomy, namely, that neither can lie
      outside the ranges observed among extant species. Thus, we further conclude that
      the CV must be used with caution when evaluating the taxonomic composition of
      fossil samples and, further, that it cannot be used to falsify a single-species
      hypothesis in any meaningful way. Other fossil hominoid samples with high
      measures of dental variation may indicate that considerable sexual size
      dimorphism typified many Eurasian middle-late Miocene hominoids.

PMID- 9929171
TI  - Lumbar anomalies in the Shanidar 3 Neandertal.
AB  - Recent examination of the Shanidar 3 remains revealed the presence of anomalous
      bilateral arthroses in the lumbar region. This paper describes this developmental
      anomaly, as well as several degenerative changes and offers potential etiologies.
      The Shanidar 3 remains represent an adult male Neandertal, approximately 35-50
      years of age, dating to the Last Glacial. Although the partial skeleton is
      fragmentary, preserved elements include an almost complete set of ribs, portions
      of all thoracic vertebrae, all lumbar vertebrae, and the sacrum. Vertebral
      articulations from S1-T1 can be confidently assigned. The vertebra designated L1
      is well preserved but lacks transverse processes. Instead, well defined bilateral
      articular surfaces, rather than transverse processes, are located on the
      pedicles. The skeletal elements associated with the anomalous L1 articulations
      were not recovered. The most likely interpretation is that the arthroses in
      question represent the facets for a 13th pair of ribs, a rare condition in modern
      hominid populations. Such lumbar developmental anomalies are an infrequent
      expression of a larger complex of cranial-caudal border shifting seen in the
      vertebral column. These shifts result in a change in the usual boundaries between
      the distinctive vertebral regions and are responsible for the majority of
      variability present in the vertebral column.

PMID- 9929172
TI  - The influence of alveolar structures on the torsional strain field in a gorilla
      corporeal cross-section.
AB  - Anthropologists have often used mandibular torsional properties to make
      inferences about primate dietary adaptations. Most of the methods employed are
      based on assumptions related to periodontal and alveolar properties. This study
      uses the finite element method to evaluate some of these assumptions with a cross
      section through the third molar of a gorilla. Results indicate that the
      properties of alveolar bone play an important role in determining the strain
      field. In comparison, the exact stiffness values of the periodontal ligaments
      seem to have a much smaller impact. Replacing the dental roots and periodontal
      ligaments with alveolar bone, however, has a significant influence on the strain
      field. It underestimates the maximum shear strain by about 28% along its
      periosteal aspect when alveoli are modeled as cortical bone. It overestimates the
      strain by a smaller amount when alveoli are modeled as trabecular bone. This
      study supports the assumption that primate mandibles behave like a closed-section
      under torsion under the limiting condition that the alveolar bone stiffness is
      more than half of the value of cortical bone; alveolar bone can then be modeled
      as cortical bone with a minimal loss of accuracy. In addition, this study
      suggests that the minimum cortical thickness should be considered for torsional
      strength. Finally, modeling accuracy can be significantly increased if both
      dental and periodontal structures can be realistically incorporated into
      mandibular biomechanical models. However, this may not be always feasible in
      studies of fossil mandibles. This is due mainly to the difficulties involved in
      estimating alveolar bone densities and in distinguishing boundaries between
      cortical bone, alveolar bone, periodontal ligaments, and dental roots in fossil
      specimens.

PMID- 9929173
TI  - Neanderthal skeleton from Tabun: U-series data by gamma-ray spectrometry.
AB  - The Neanderthal hominid Tabun C1, found in Israel by Garrod & Bate, was
      attributed to either layer B or C of their stratigraphic sequence. We have used
      gamma-ray spectrometry to determine the 230Th/234U and 231Pa/235U ratios of two
      bones from this skeleton, the mandible and a femur. The ages calculated from
      these ratios depend on the uranium uptake history of the bones. Assuming a model
      of early U (EU) uptake the age of the Tabun C1 mandible is 34+/-5 ka. The EU age
      of the femur is 19+/-2 ka. The femur may have experienced continuous (linear) U
      uptake which would give an age of 33+/-4 ka, in agreement with the mandible's EU
      age, but implies marked inhomogeneity in U uptake history at the site. These new
      age estimates for the skeleton suggest that it was younger than deposits of layer
      C. This apparent age is less than those of other Neanderthals found in Israel,
      and distinctly younger than the ages of the Skhul and Qafzeh burials. This
      suggests that Neanderthals did not necessarily coexist with the earliest modern
      humans in the region. All of the more complete Neanderthal fossils from Israel
      are now dated to the cool period of the last glacial cycle, suggesting that
      Neanderthals may have arrived in this region as a result of the southward
      expansion of their habitable range. The young age determined for the Tabun
      skeleton would suggest that Neanderthals survived as late in the Levant as they
      did in Europe.

PMID- 9929174
TI  - A new reconstruction of the Le Moustier 1 skull and investigation of internal
      structures using 3-D-muCT data.
AB  - Using the non-destructive technique of 3-D micro computed tomography (3-D
      microCT), we present a new, virtual reconstruction of the Le Moustier 1
      Neandertal skull. This new reconstruction corrects defects found in earlier
      reconstruction attempts by repositioning misaligned cranial fragments, addressing
      the problem of asymmetry caused by pressure during the fossilization process, and
      placing the basioccipital in its proper anatomical position. Metric comparisons
      between Le Moustier 1 and juvenile and adult Neandertals demonstrate that facial
      height proceeded at a faster rate of growth than facial prognathism at the
      beginning of the adolescent period. They also confirm the anterior placement of
      the basioccipital. A compound painted to match the colour of the fossilized bone
      was used in previous reconstruction attempts and the aim of this analysis was to
      remove the false material to reveal to what extent the fossilized bone was
      preserved. The areas with the most artificial material and glue include the
      palate, areas around the mandibular teeth, the left frontal, and parts of the
      right parietal and temporal bones. The microCT data were also used to examine
      internal structures of the skull including the frontal sinus and the labyrinth of
      the inner ear. An investigation of the frontal sinus reveals morphology similar
      to that found in adult Neandertals, although the structure does not extend to mid
      orbit. The dimension of the radius of curvature of the lateral semicircular canal
      falls within one standard deviation, and the anterior and posterior canals within
      two standard deviations, of the published Neandertal mean. As in other
      Neandertals, the posterior semicircular canal is in an inferior position relative
      to the plane of the lateral canal.

PMID- 9929175
TI  - Health and the national information infrastructure.

PMID- 9929176
TI  - The next generation Internet and health care: a civics lesson for the informatics
      community.
AB  - The Internet provides one of the most compelling examples of the way in which
      government research investments can, in time, lead to innovations of broad social
      and economic impact. This paper reviews the history of the Internet's evolution,
      emphasizing in particular its relationship to medical informatics and to the
      nation's health-care system. Current national research programs are summarized
      and the need for more involvement by the informatics community and by federal
      health-care agencies is emphasized.

PMID- 9929177
TI  - G7: a framework for international cooperation in medical informatics.
AB  - The world's major economic powers, the G7, have initiated a collaborative
      International research and demonstration program to exploit the benefits of
      information and communications technology for society. The Global Healthcare
      Applications Project (GHAP) is investigating a variety of informatics
      applications in disease specific domains, telemedicine, and multilingual textual
      and image database systems. This paper summarizes the nine GHAP sub-projects
      undertaken to date, with emphasis on those in which the U.S. is a participant.
      The growing use of smart card technology, especially in Europe, is adding new
      impetus for similar medical and health experiments in the U.S. A pilot project
      now underway in several Western states is described.

PMID- 9929178
TI  - Clinical information systems for integrated healthcare networks.
AB  - In the 1990's, a large number of hospitals and medical practices have merged to
      form integrated healthcare networks (IHN's). The nature of an IHN creates new
      demands for information management, and also imposes new constraints on
      information systems for the network. Important tradeoffs must be made between
      homogeneity and flexibility, central and distributed governance, and access and
      confidentiality. This paper describes key components of clinical information
      systems for IHN's, and examines important design decisions that affect the value
      of such systems.

PMID- 9929179
TI  - Interface design for health care environments: the role of cognitive science.
AB  - An important challenge in the development of computer-based health care
      environments is the design of effective user interfaces. In this paper we
      consider a number of aspects of interface design related to the study of human
      computer interaction from a cognitive perspective. It is argued that user
      interfaces must be designed with consideration of the information requirements,
      cognitive capabilities and limitations of the end users. Greater concern for
      fundamental research in design of user interfaces is also needed to complement
      short-term goals and approaches to improving user interfaces. Towards these
      objectives, several emerging trends are beginning to have an important impact in
      the design of health care interfaces. This includes the recognition of the need
      for iterative design and evaluation of user interfaces, applying theoretical
      frameworks and methods from cognitive science. An understanding of distributed as
      well as individual cognition will also become critical in the development of
      effective user interfaces as access to health care systems becomes increasingly
      widespread.

PMID- 9929180
TI  - Information retrieval at the millenium.
AB  - Information retrieval systems were among the first medical informatics
      applications, yet their use has changed substantially in this decade with the
      growth of end-user computers and the Internet. While early challenges revolved
      around how to increase the amount of information available in electronic form,
      more recent challenges center on how to manage the growing volume. Traditional
      information retrieval issues--such as how to organize and index information to
      make it more retrievable as well as how to evaluate the effectiveness of systems-
      are still as pertinent as ever.

PMID- 9929181
TI  - Modern architectures for intelligent systems: reusable ontologies and problem
      solving methods.
AB  - When interest in intelligent systems for clinical medicine soared in the 1970s,
      workers in medical informatics became particularly attracted to rule-based
      systems. Although many successful rule-based applications were constructed,
      development and maintenance of large rule bases remained quite problematic. In
      the 1980s, an entire industry dedicated to the marketing of tools for creating
      rule-based systems rose and fell, as workers in medical informatics began to
      appreciate deeply why knowledge acquisition and maintenance for such systems are
      difficult problems. During this time period, investigators began to explore
      alternative programming abstractions that could be used to develop intelligent
      systems. The notions of "generic tasks" and of reusable problem-solving methods
      became extremely influential. By the 1990s, academic centers were experimenting
      with architectures for intelligent systems based on two classes of reusable
      components: (1) domain-independent problem-solving methods-standard algorithms
      for automating stereotypical tasks--and (2) domain ontologies that captured the
      essential concepts (and relationships among those concepts) in particular
      application areas. This paper will highlight how intelligent systems for diverse
      tasks can be efficiently automated using these kinds of building blocks. The
      creation of domain ontologies and problem-solving methods is the fundamental end
      product of basic research in medical informatics. Consequently, these concepts
      need more attention by our scientific community.

PMID- 9929182
TI  - Bioinformatics in support of molecular medicine.
AB  - Bioinformatics studies two important information flows in modern biology. The
      first is the flow of genetic information from the DNA of an individual organism
      up to the characteristics of a population of such organisms (with an eventual
      passage of information back to the genetic pool, as encoded within DNA). The
      second is the flow of experimental information from observed biological phenomena
      to models that explain them, and then to new experiments in order to test these
      models. The discipline of bioinformatics has its roots in a number of activities,
      including the organization of DNA sequence and protein three-dimensional
      structural data collections in the 1960's and 1970's. It has become a booming
      academic and industrial enterprise with the introduction of biological
      experiments that rapidly produce massive amounts of data (such as the multiple
      genome sequencing projects, the large scale analysis of gene expression, and the
      large scale analysis of protein-protein interactions). Basic biological science
      has always had an impact on clinical medicine (and clinical medical information
      systems), and is creating a new generation of epidemiologic, diagnostic,
      prognostic, and treatment modalities. Bioinformatics efforts that appear to be
      wholly geared towards basic science are likely to become relevant to clinical
      informatics in the coming decade. For example, DNA sequence information and
      sequence annotations will appear in the medical chart with increasing frequency.
      The algorithms developed for research in bioinformatics will soon become part of
      clinical information systems.

PMID- 9929183
TI  - Clinical data exchange standards and vocabularies for messages.
AB  - Motivation for the creation of electronic data interchange (message) standards is
      discussed. The ISO Open Systems Interface model is described. Clinical
      information models, message syntax and structure, and the need for a standardized
      coded vocabulary are explained. The HIPAA legislation and subsequent HHS
      transaction recommendations are reviewed. The history and mission statements of
      six of the most popular message development organizations (MDOs) are summarized,
      and the data exchange standards developed by these organizations are listed. The
      organizations described include Health Level Seven (HL7), American Standards for
      Testing and Materials (ASTM) E31, Digital Image Communication in Medicine
      (DICOM), European Committee for Standardization (Comite Europeen de
      Normalisation), Technical Committee for Health Informatics (CEN/TC 251), the
      National Council for Prescription Drug Programs (NCPDP), and Accredited Standards
      Committee X12 Insurance Subcommittee (X12N). The locations of Internet web sites
      for the six organizations are provided as resources for further information.

PMID- 9929184
TI  - The Copernican era of healthcare terminology: a re-centering of health
      information systems.
AB  - Health terminology and classifications have been an unseen backwater in
      healthcare practice and information systems development. Today however, the
      recognized need for comparable patient data is driving a new discovery about its
      strategic importance. Consistent patient descriptions and concept-centered data
      representations are crucial for efficient discovery of optimal treatments, best
      outcomes, and efficient practice patterns. The fabled linkage of knowledge
      sources at the time and place of care requires the conceptual intermediary of
      common terminology. A brief history overviewing the evolution of health
      classifications will provide the foundation for considering present and evolving
      health terminology developments. Their roles in health information systems will
      be characterized. Discussion will focus on the likely influences of the HIPAA
      legislation nationally and the new ISO Healthcare Informatics Technical Committee
      internationally, on terminology adaptation and incorporation.

PMID- 9929185
TI  - LifeLines: using visualization to enhance navigation and analysis of patient
      records.
AB  - LifeLines provide a general visualization environment for personal histories. We
      explore its use for clinical patient records. A Java user interface is described,
      which presents a one-screen overview of a computerized patient record using
      timelines. Problems, diagnoses, test results or medications can be represented as
      dots or horizontal lines. Zooming provides more details; line color and thickness
      illustrate relationships or significance. The visual display acts as a giant
      menu, giving direct access to the data.

PMID- 9929186
TI  - Clinical data entry.
AB  - Routine capture of patient data for a computer-based patient record system
      remains a subject of study. Time constraints that require fast data entry and
      maximal expression power are in favor of free text data entry. However, using
      patient data directly for decision support systems, for quality assessment, etc.
      requires structured data entry, which appears to be more tedious and time
      consuming. In this paper, a prototype clinical data entry application is
      described that combines free text and structured data entry in one single
      application and allows clinicians to smoothly switch between these two different
      input styles. A knowledge base involving a semantic network of clinical data
      entry terms and their properties and relationships is used by this application to
      support structured data entry. From structured data, sentences are generated and
      shown in a text processor together with the free text. This presentation metaphor
      allows for easy integrated presentation of structured data and free text.

PMID- 9929187
TI  - User interface preferences in a point-of-care data system.
AB  - Point-of-care data entry is an important part of a clinical information system.
      Unfortunately, many health care providers refuse to perform data entry because
      they feel computers are difficult to use and require more time than traditional
      paper based forms. We designed a user interface for entry of outpatient visit
      information that gives the health care provider several alternative methods of
      entering data. The system audits the use of the individual interface elements and
      measures the time required for completion of the data entry.

PMID- 9929188
TI  - Identification of design features to enhance utilization and acceptance of
      systems for Internet-based decision support at the point of care.
AB  - Extensive utilization of point-of-care decision support systems will be largely
      dependent on the development of user interaction capabilities that make them
      effective clinical tools in patient care settings. This research identified
      critical design features of point-of-care decision support systems that are
      preferred by physicians, through a multi-method formative evaluation of an
      evolving prototype of an Internet-based clinical decision support system.
      Clinicians used four versions of the system--each highlighting a different
      functionality. Surveys and qualitative evaluation methodologies assessed
      clinicians' perceptions regarding system usability and usefulness. Our analyses
      identified features that improve perceived usability, such as telegraphic
      representations of guideline-related information, facile navigation, and a
      forgiving, flexible interface. Users also preferred features that enhance
      usefulness and motivate use, such as an encounter documentation tool and the
      availability of physician instruction and patient education materials. In
      addition to identifying design features that are relevant to efforts to develop
      clinical systems for point-of-care decision support, this study demonstrates the
      value of combining quantitative and qualitative methods of formative evaluation
      with an iterative system development strategy to implement new information
      technology in complex clinical settings.

PMID- 9929189
TI  - Potential for meeting clinician information requirements in an intensive care
      unit (ICU) via the web.
AB  - OBJECTIVE: A web interface allows ICU-oriented information to be accessed from
      other patient care areas and clinical applications, optimizing information
      integration in the hospital. In preparation for installation of a web-enabled
      bedside patient charting application, we attempted to maximize the percentage of
      our ICU-information requirements that could be met via the web and designed a web
      interface for accessing this information. DESIGN: A comprehensive inventory of
      the information needs of our ICU was made by taking an inventory of existing
      paper and electronic documents, manuals, handouts, patient chart elements, and
      clinician communication about patients. We then designed a web site, created web
      based prototype applications, and linked to hospital web applications.
      MEASUREMENTS: Before and after implementation of the web site, each category of
      requirements that were identified were marked as available, partially available,
      or unavailable via the web. RESULTS: After implementation of the ICU web site,
      56.3% of identified information category requirements (+18.3%) were available via
      the web, 23.9% were partially available (+4.2%) and 19.8% were still unavailable
      (-22.5%). Implementation of the web-enabled bedside charting application would
      increase the percentage of information categories available via the web to 73.2%
      (+16.9%) and 18.3% of required information would be partially web-accessible.
      CONCLUSIONS: The majority of information required by clinicians in an ICU can be
      made accessible via the web if a systematic approach is taken to identify needs
      and to develop or link to applications and web pages to meet these needs.

PMID- 9929190
TI  - Using web technology and Java mobile software agents to manage outside referrals.
AB  - A prototype, web-based referral application was created with the objective of
      providing outside primary care providers (PCP's) the means to refer patients to
      the Massachusetts General Hospital and the Brigham and Women's Hospital. The
      application was designed to achieve the two primary objectives of providing the
      consultant with enough data to make decisions even at the initial visit, and
      providing the PCP with a prompt response from the consultant. The system uses a
      web browser/server to initiate the referral and Java mobile software agents to
      support the workflow of the referral. This combination provides a light client
      implementation that can run on a wide variety of hardware and software platforms
      found in the office of the PCP. The implementation can guarantee a high degree of
      security for the computer of the PCP. Agents can be adapted to support the wide
      variety of data types that may be used in referral transactions, including
      reports with complex presentation needs and scanned (faxed) images Agents can be
      delivered to the PCP as running applications that can perform ongoing queries and
      alerts at the office of the PCP. Finally, the agent architecture is designed to
      scale in a natural and seamless manner for unforeseen future needs.

PMID- 9929191
TI  - Clinical event management using push technology--implementation and evaluation at
      two health care centers.
AB  - For two years, beginning in 1995, we developed and implemented a novel method for
      delivering patient information directly to clinicians. Using rules based logic to
      scan data bound for an electronic medical record, messages were automatically
      written that alert care providers to important patient information. These
      messages were transmitted electronically to either existing email accounts or to
      wide-screen pagers, or to both. This system now is operational at two medical
      centers. We describe the model and methods that led to its successful
      implementation and compare it to other ways of delivering patient information.

PMID- 9929192
TI  - The effect of telemedicine on neonatal intensive care unit length of stay in very
      low birthweight infants.
AB  - OBJECTIVE: This study addresses the effect of the installation and use of a
      telecardiology system on the intensive care length of stay of very low
      birthweight (VLBW) newborn infants. DESIGN: A retrospective comparison of 314
      VLBW infants admitted to one of two neonatal intensive care units for a three
      year period from calendar years 1994 through 1996. A regression model was
      constructed to predict the intensive care length of stay while controlling for
      known risk factors. RESULTS: Telemedicine's effect is to reduce the intensive
      care length of stay and it both statistically significant (p < 0.05) and
      practically significant, reducing the intensive care length of stay by over 17%.
      The reduction in length of stay is greater at lower birthweights. CONCLUSIONS:
      Under the circumstances present in this study, telemedicine has been an effective
      intervention to reduce the intensive care length of stay.

PMID- 9929193
TI  - Component architecture for web based EMR applications.
AB  - The World Wide Web provides the means for the collation and display of
      disseminated clinical information of use to the healthcare provider. However, the
      heterogeneous nature of clinical data storage and formats makes it very difficult
      for the physician to use one consistent client application to view and manipulate
      information. Similarly, developers are faced with a multitude of possibilities
      when creating interfaces for their users. A single patients records may be
      distributed over a number of different record keeping systems, and/or a physician
      may see patients whose individual records are stored at different sites. Our goal
      is to provide the healthcare worker with a consistent application interface
      independent of the parent database and at the same time allow developers the
      opportunity to customize the GUI in a well controlled, stable application
      environment.

PMID- 9929194
TI  - Architecture for a Web-based clinical information system that keeps the design
      open and the access closed.
AB  - We are developing the Patient Clinical Information System (PatCIS) project at
      Columbia-Presbyterian Medical Center to provide patients with access to health
      information, including their own medical records (permitting them to contribute
      selected aspects to the record), educational materials and automated decision
      support. The architecture of the system allows for multiple, independent
      components which make use of central services for managing security and usage
      logging functions. The design accommodates a variety of data entry, data display
      and decision support tools and provides facilities for tracking system usage and
      questionnaires. The user interface minimizes hypertext-related disorientation and
      cognitive overload; our success in this regard is the subject of on-going
      evaluation.

PMID- 9929195
TI  - Use of the WWW for distributed knowledge engineering for an EMR: the
      KnowledgeBank concept.
AB  - Developing automated tools for clinical information management requires an
      appreciation of user needs and capabilities. To address the reality of practice
      style variation, and the varying degree of comfort with computers in clinical
      users, we developed the KnowledgeBank concept. The KnowledgeBank concept includes
      an end-user authoring tool for clinical content in the EMR, and a web-based
      repository of content for sharing clinical content. We describe the early
      experiences of end-users using the KnowledgeBank.

PMID- 9929196
TI  - Development of a web based electronic patient record extending accessibility to
      clinical information and integrating ancillary applications.
AB  - Web-technology offers a powerful mechanism for providing access to clinic
      information. Applications need no longer to be tied to a specific client
      operating system. The Johns Hopkins Hospital has designed a web based electronic
      patient record system which seamlessly incorporates multiple web sites. This
      paper will discuss the motivations for building the system, the architecture, and
      the challenges faced in designing the architecture.

PMID- 9929197
TI  - Mobile workers in healthcare and their information needs: are 2-way pagers the
      answer?
AB  - The ability to have access to information relevant to patient care is essential
      within the healthcare environment. To meet the information needs of its workers,
      healthcare information systems must fulfill a variety of functional requirements.
      One of these requirements is to define how workers will interact with the system
      to gain the information they need. Currently, most healthcare information systems
      rely on users querying the system via a fixed terminal for the information they
      desire; a method that is inefficient because there is no guarantee the
      information will be available at the time of their query and it interrupts their
      work flow. In general, clinical event monitors--systems whose efficacy relies on
      the delivery of time-critical information--have used e-mail and numeric pagers as
      their methods to deliver information. Each of these methods, however, still
      requires the user to perform additional steps, i.e., log into an information
      system in order to attain the information about which the system is alerting
      them. In this paper we describe the integration and use of 2-way alphanumeric
      pagers in CLEM, the UPMC Health System's Clinical Event Monitor, and how the use
      of these pagers addresses the information needs of mobile workers in healthcare.

PMID- 9929198
TI  - Preferences of interns and residents for E-mail, paging, or traditional methods
      for the delivery of different types of clinical information.
AB  - We elicited from medical house staff their preferences for e-mail and
      alphanumeric pager as communication channels for the delivery of 18 different
      types of clinical information about their inpatients. For each type, we
      calculated the proportion of users who preferred delivery by e-mail, pager, both,
      or neither (usual delivery). For 14/18 (78%) types, more users preferred delivery
      by pager than by the other options. For 2/18 (11%) types, e-mail was preferred.
      For 2/18 (11%) types, more users preferred redundant delivery using both
      channels. For no types did more users prefer neither, meaning that the
      information would be delivered by traditional channels, if any. We conclude that
      medical house staff in the inpatient setting prefer to receive many types of
      clinical information by pager. The reason may be that they otherwise would have
      to query clinical information systems for these data, which is wasteful of their
      time and introduces delays into the process of care. Additionally, we found
      significant inter-user variability, suggesting that it may be useful for the
      notification services of an enterprise to employ user profiles for the delivery
      of clinical information.

PMID- 9929199
TI  - Development of a clinical event monitor for use with the Veterans Affairs
      Computerized Patient Record System and other data sources.
AB  - We are developing an event monitor to operate with the Veterans Affairs
      Computerized Patient Record System (CPRS). The event monitor is designed to
      receive messages when important patient events such as posting of new results,
      patient movement, and orders occur. Our design separates the event monitor from
      CPRS itself, using communication via a network connection to receive HL7
      messages, to access other data needed to run rules, and to communicate with
      providers by message display, electronic mail and other mechanisms. Results from
      operation of the event monitor using patient data in our test account show that a
      wide variety of data can be accessed by the event monitor with acceptable
      response times.

PMID- 9929200
TI  - The effects of an Electronic Medical Record on patient care: clinician attitudes
      in a large HMO.
AB  - OBJECTIVE: The purpose of this study is to examine the attitudes of clinicians in
      a large HMO toward the effect of an outpatient Electronic Medical Record system
      on the quality of patient care. Attitudes toward a Results Reporting system and
      an online charting and ordering system are also compared. DESIGN: A cross
      sectional study was performed using a survey of Kaiser Permanente Northwest
      clinicians. In addition, interviews were conducted with the physician leaders of
      the clinical departments at Kaiser Permanente Northwest. MEASUREMENTS: Clinician
      attitudes are measured regarding the effects of a Results Reporting system and an
      online charting and ordering system on the overall quality of patient care and
      other care-related indices. RESULTS: Most clinicians feel that the outpatient
      Electronic Medical Record has improved the overall quality of patient care, with
      72% reporting an improvement with the use of the Results Reporting system, and
      60% reporting an improvement with the use of the online charting and ordering
      system. On average, clinicians feel that the EMR has also improved the quality of
      the patient-clinician interaction, the ability to coordinate the care of patients
      with other departments, the ability to detect medication errors, the timeliness
      of referrals, and the ability to act on test results in a timely fashion.
      CONCLUSION: Clinicians perceive an improvement in patient care as a result of
      using an outpatient Electronic Medical Record system. Clinicians have higher
      opinions, however, of the effects of a Results Reporting system compared to an
      online charting and ordering system.

PMID- 9929201
TI  - Knowledge-based visualization of time-oriented clinical data.
AB  - We describe a domain-independent framework (KNAVE) specific to the task of
      interpretation, summarization, visualization, explanation, and interactive
      exploration in a context-sensitive manner through time-oriented raw clinical data
      and the multiple levels of higher-level, interval-based concepts that can be
      abstracted from these data. The KNAVE exploration operators, which are
      independent of any particular clinical domain, access a knowledge base of
      temporal properties of measured data and interventions that is specific to the
      clinical domain. Thus, domain-specific knowledge underlies the domain-independent
      semantics of the interpretation, visualization, and exploration processes.
      Initial evaluation of the KNAVE prototype by a small number of users with
      variable clinical and informatics training has been encouraging.

PMID- 9929202
TI  - Mining biomedical time series by combining structural analysis and temporal
      abstractions.
AB  - This paper describes the combination of Structural Time Series analysis and
      Temporal Abstractions for the interpretation of data coming from home monitoring
      of diabetic patients. Blood Glucose data are analyzed by a novel Bayesian
      technique for time series analysis. The results obtained are post-processed using
      Temporal Abstractions in order to extract knowledge that can be exploited "at the
      point of use" from physicians. The proposed data analysis procedure can be viewed
      as a Knowledge Discovery in Data Base process that is applied to time-varying
      data. The work here described is part of a Web-based telemedicine system for the
      management of Insulin Dependent Diabetes Mellitus patients, called T-IDDM.

PMID- 9929203
TI  - The evolution of an integrated timeline for oncology patient healthcare.
AB  - The introduction of computers in the medical environment has contributed to the
      proliferation of medical data, often making it difficult to consolidate
      information on a single patient. In patients with complex medical problems, such
      as oncology patients, the lack of data integration can negatively impact on
      patient care. This paper presents an infrastructure for the creation of an
      integrated multimedia timeline that automatically combines patient information
      from distributed hospital information sources, and creates a visual summary of
      pertinent events in a patient's medical history. In this prototype, we focus on
      oncology patients under treatment for advanced cancers.

PMID- 9929204
TI  - Temporal representation design principles: an assessment in the domain of liver
      transplantation.
AB  - Time modeling is an important aspect of medical decision-support systems
      engineering. At the core of effective time modeling lies the challenge of proper
      knowledge representation design. In this paper, we focus on two important
      principles for effective time-modeling languages: (a) hybrid temporal
      representation, and (b) dynamic temporal abstraction. To explore the significance
      of these design principles, we extend a previously-defined formalism (single
      granularity modifiable temporal belief networks--MTBN-SGs) to accommodate
      multiple temporal granularities and dynamic query and domain-specific model
      creation. We call the new formalism multiple-granularity MTBNs (MTBN-MGs). We
      develop a prototype system for modeling aspects of liver transplantation and
      analyze the resulting model with respect to its representation power,
      representational tractability, and inferential tractability. Our experiment
      demonstrates that the design of formalisms is crucial for effective time
      modeling. In particular: (i) Hybrid temporal representation is a desirable
      property of time-modeling languages because it makes knowledge acquisition
      easier, and increases representational tractability. (ii) Dynamic temporal
      abstraction improves inferential and representational tractability significantly.
      We discuss a high-level procedure for extending existing languages to incorporate
      hybrid temporal representation and dynamic temporal abstraction.

PMID- 9929205
TI  - MYCIN II: design and implementation of a therapy reference with complex content
      based indexing.
AB  - We describe the construction of MYCIN II, a prototype system that provides for
      content-based markup and search of a forthcoming clinical therapeutics textbook,
      Antimicrobial Therapy and Vaccines. Existing commercial search technology for
      digital references utilizes generic tools such as textword-based searches with
      geographical or statistical refinements. We suggest that the drawbacks of such
      systems significantly restrict their use in everyday clinical practice. This is
      in spite of the fact that there is a great need for the information contained
      within these same references. The system we describe is intended to supplement
      keyword searching so that certain important questions can be asked easily and can
      be answered reliably (in terms of precision and recall). Our method attacks this
      problem in a restricted domain of knowledge-clinical infectious disease. For
      example, we would like to be able to answer the class of questions exemplified by
      the following query: "What antimicrobial agents can be used to treat endocarditis
      caused by Eikenella corrodens?" We have compiled and analyzed a list of such
      questions to develop a concept-based markup scheme. This scheme was then applied
      within an HTML markup to electronically "highlight" passages from three textbook
      chapters. We constructed a functioning web-based search interface. Our system
      also provides semi-automated querying of PubMed using our concept markup and the
      user's actions as a guide.

PMID- 9929206
TI  - Using computer modeling to help identify patient subgroups in clinical data
      repositories.
AB  - OBJECTIVE: The ability to accurately and efficiently identify patient cases of
      interest in a hospital information system has many important clinical, research,
      educational and administrative uses. The identification of cases of interest
      sometimes can be difficult. This paper describes a two-stage method for searching
      for cases of interest. DESIGN: First, a Boolean search is performed using coded
      database variables. The user classifies the retrieved cases as being of interest
      or not. Second, based on the user-classified cases, a computer model of the
      patient cases of interest is constructed. The model is then used to help locate
      additional cases. These cases provide an augmented training set for constructing
      a new computer model of the cases of interest. This cycle of modeling and user
      classification continues until halted by the user. MEASUREMENTS: This paper
      describes a pilot study in which this method is used to identify the records of
      patients who have venous thrombosis. RESULTS: The results indicate that computer
      modeling enhances the identification of patient cases of interest.

PMID- 9929207
TI  - Evaluating a computerized tool for coding patient information.
AB  - OBJECTIVE: Computerized tools may be useful in speeding up and facilitating the
      laborious task of coding patient information. This paper describes a method of
      objectively evaluating their efficiency. DESIGN: 38 study subjects were randomly
      assigned to a manual coding group or an automated coding group, with
      stratification according to two variables (used to coding yes/no, physician
      yes/no). Subjects then coded the same standardized set of diagnoses in a limited
      time. The numbers of exact codes retrieved were compared using a global analysis
      of variance model. RESULTS: The two groups were not significantly different with
      regard to the number of physicians (p = 0.74) and the number of usual coders (p =
      0.52) they included. Significantly more exact codes were achieved in the group
      using automated coding than among the manual group (p = 0.04). Physicians were
      significantly more efficient at coding than non-physicians (p = 0.02).
      CONCLUSION: This study describes an objective means of evaluating the performance
      of an automated coding tool. It shows that better results were achieved with the
      computerised compared to the manual method, even when the superior abilities of
      physicians were taken into account.

PMID- 9929208
TI  - Self-contained patient data in ORCA to cope with an evolving vocabulary.
AB  - Because of the benefits of standardization in healthcare data for research,
      decision support, and quality assessment, much research effort focuses on
      collection of structured patient data. Many strategies to obtain such data are
      based on controlled vocabularies to guide data entry in a far more flexible way
      than a fixed-form approach. Medical controlled vocabularies evolve, but change is
      difficult to reconcile with standardization. Retrieval of data, collected with
      different versions of vocabularies, is not straightforward and has consequences
      for patient care and research. There are several strategies to cope with these
      problems: keep each version, keep a record of changes, or conversion of
      previously collected data. Each of these strategies has pros and cons regarding
      storage consumption, performance during patient care, and research. The approach
      in ORCA (Open Record for Care) is based on self-contained patient data and
      combines the strengths of these strategies.

PMID- 9929209
TI  - Qualification of discordant responses in utility assessment.
AB  - In many studies of utility assessment, the discordant response rate is
      significantly high. Discordant responses suggest inconsistency and, in turn,
      suggest inaccurate measurement of personal values that can lead to erroneous
      medical recommendations. The most common method of dealing with these responses
      is to exclude them from the sample statistics as incoherent or confused
      respondents. This paper proposes another perspective on discordant responses. In
      a recent study eliciting utility values for states of health that follow stroke,
      we observed a high rate of discordant responses. Closer examination of these
      discordant responses reveals that discordant responses are not all alike. Simple
      qualitative and quantitative views of these differences suggest that there may be
      information outside the concordant population of responses, which is lost by
      their exclusion. In an effort to understand the elevated discordant response
      rate, the effect of relaxing the defining boundaries of a discordant response was
      explored.

PMID- 9929210
TI  - Renewing information infrastructure at Hospital das Clinicas.
AB  - In this paper we describe the process of renewing the Informatics infrastructure
      of Sao Paulo University Medical School Hospital, a very complex environment. Our
      proposal consists of a change in the paradigm of Informatics and the use of
      Information Technology in the hospital. That change aims at making information
      available to the hospital, its managers, health care workers and patients. The
      paradigm change is reflected in every aspect of the new infrastructure: human
      resources, methods, and organizational structure, as we intend to demonstrate in
      this paper. This process is expected to be concluded by the end of this year,
      yielding benefits regarding costs, efficiency, and better patient care.

PMID- 9929211
TI  - Costs and benefits of connecting community physicians to a hospital WAN.
AB  - The Washington Heights-Inwood Community Health Management Information System
      (WHICHIS) at the Columbia-Presbyterian Medical Center (CPMC) provides 15
      community physician practices with seamless networking to the CPMC Wide-Area
      Network. The costs and benefits of the project were evaluated. Installation
      costs, including hardware, office management software, cabling, network routers,
      ISDN connection and personnel time, averaged $22,902 per office. Maintenance and
      support costs averaged $6,293 per office per year. These costs represent a "best
      case" scenario after a several year learning curve. Participating physicians were
      interviewed to assess the impact of the project. Access to the CPMC Clinical
      Information System (CIS) was used by 87%. Other resource usage was: non-CPMC Web
      based resources, 80%; computer billing, 73%; Medline and drug information
      databases, 67%; and, electronic mail, 60%. The most valued feature of the system
      was access to the CPMC CIS. The second most important was the automatic
      connection provided by routed ISDN. Frequency of access to the CIS averaged 6.67
      days/month. Physicians reported that the system had significantly improved their
      practice of medicine. We are currently exploring less expensive options to
      provide this functionality.

PMID- 9929212
TI  - A software architecture to support a large-scale, multi-tier clinical information
      system.
AB  - A robust software architecture is necessary to support a large-scale multi-tier
      clinical information system. This paper describes our mechanism for enterprise
      distribution of applications and support files, the consolidation of data-access
      functions and system utilities stored on the data access tier, and an application
      framework which implements a coherent clinical computing environment. The
      software architecture and systems described in this paper have been robust
      through pilot testing of our applications at Massachusetts General Hospital.

PMID- 9929213
TI  - Social equity and access to the World Wide Web and E-mail: implications for
      design and implementation of medical applications.
AB  - INTRODUCTION: The distribution and types of Internet connectivity will determine
      the equity of access by patient populations to emerging health technologies. We
      sought to measure the rates, types, and predictors of access in a patient
      population targeted for Web-based medical services. METHODS: Design. Cross
      sectional in-person interview. Setting. Emergency department of a large urban
      pediatric teaching hospital. Subjects. Primary caretakers of patients or patients
      at least 16 years old. Procedure and measures. Subjects were asked about access
      to e-mail and the Internet as well as about willingness to use and concerns about
      Web-based services. Views of equity and access and sociodemographic data were
      also elicited. RESULTS: 132 subjects were enrolled in the study. Of respondents,
      67.2% use a computer and 36.4% can access the Internet or e-mail from home.
      Including Internet connections and/or e-mail accounts at work, school and public
      libraries, 50.7% of the sample has access. Forty percent of families have e-mail
      accounts. The rate at which families have connectivity is primarily correlated
      with income (r = 0.6, p < 0.01). At all income levels, rates of access to the
      World Wide Web are higher than to e-mail. White patients are much more likely to
      have e-mail (OR 5.0, 95% CI 2.4-10.8) and Web access (OR 3.6, 95% CI 1.7-7.5).
      CONCLUSIONS: Connectivity is directly correlated with income and distributed
      unevenly across racial and ethnic groups. World Wide Web access is more prevalent
      than e-mail accounts, and both are often obtained outside the home. Design of
      health applications should account for these attributes of patient access.

PMID- 9929214
TI  - Towards improving the accuracy of the clinical database: allowing outpatients to
      review their computerized data.
AB  - We developed an application that allowed patients coming to the clinic to review
      on a paper form their computerized health maintenance, medication, and allergy
      data. The patient could edit the paper form and the physician then could enter
      the new data into the database. We implemented the system in 4 clinics (17 MDs)
      To evaluate the system, we reviewed 80 forms from one physician's patients to
      determine how often patients provided new data. We also sent questionnaires to
      the physicians asking for their estimates of how often there was new data and for
      their impression of the system. We interviewed secretaries in the clinics about
      logistical issues. Of the 80 forms, 29 (36%) had new data; 28% had new health
      maintenance data and 19% had new medication data. The 7 physicians who responded
      to the questionnaire estimated that new health maintenance data were present on
      22% of the forms. The physicians who responded to the questionnaire felt the
      system was useful. The secretaries said that managing the paper flow in the
      clinic was often unwieldy and in some clinics, the system has been abandoned or
      is used intermittently. Having patients review their data is one avenue to
      improving the accuracy of computerized records.

PMID- 9929215
TI  - Pre- and post-control model research on end-users' satisfaction with an
      electronic medical record: preliminary results.
AB  - This study reports early results of a project that addresses the process of
      computerizing medical records in multiple ambulatory care sites of a health
      system. The study focuses on end-user attitudes before, during, and after
      implementation, through the use of questionnaires, interviews, and participant
      observation. Knowledge about end-user attitudes prior to computerization may
      contribute to planning for the training and implementation process. Tailoring
      these processes to meet the varying needs of user groups may result in a higher
      level of functional use of the system and less stress to the persons involved in
      its use. One implementation plan may not work for all sites when there are
      differences in size of the clinic, work flow patterns prior to implementation,
      and computer experience among personnel. Preliminary analysis of post
      installation questionnaires and interviews six months after the installation
      point to a number of areas that might be usefully addressed in future
      installation efforts.

PMID- 9929216
TI  - Moving towards an electronic patient record: a survey to assess the needs of
      community family physicians.
AB  - OBJECTIVE: To determine the needs of community family physicians regarding
      electronic patient records (EPRs). DESIGN: A comprehensive survey was sent to 101
      community family physicians in Hamilton, Ontario, who had expressed an interest
      in EPRs. RESULTS: 46 physicians responded (46%). 87% felt that an EPR would
      result in their providing better patient care. A wide variety of items were
      deemed to be important to be included on the EPR "front page". Desired
      functionality emphasized labs, medications, consultation, hospital follow-up and
      health maintenance. Family physicians tended to prefer templates to other data
      entry methods such as typing and dictating. Respondents were more willing to view
      information from the hospital than to let the hospital view information from
      their own offices. CONCLUSION: This survey provided useful information on the
      perceived EPR needs of community-based family physicians. It will be repeated
      post-computerization.

PMID- 9929217
TI  - Physician order entry in U.S. hospitals.
AB  - OBJECTIVE: Determine the percent of U.S. hospitals where computerized physician
      order entry (POE) is available and the extent of its use. METHODS: A survey was
      sent to a systematic sample of 1,000 U.S. hospitals asking about availability of
      POE, whether usage is required, percent of physicians using it, and percent of
      orders entered by computer. RESULTS: About 66% do not have POE available. Of the
      32.1% that have it completely or partially available, 4.9% require its usage,
      over half report usage by under 10% of physicians, and over half report that
      fewer than 10% of orders are entered this way. Analysis of comments showed that
      many hospitals have POE available for use by non-physicians only, but that they
      hope to offer it to physicians after careful planning. CONCLUSION: Most U.S.
      hospitals have not yet implemented POE. Complete availability throughout the
      hospital is rare, very few require its use, low percentages of physicians are
      actual users, and low percentages of orders are entered this way. On a national
      basis, computerized order entry by physicians is not yet widespread.

PMID- 9929218
TI  - What is an electronic patient record?
AB  - While organizations develop their Electronic Patient Records, there will be a
      transition period during which computerized and paper records will both exist,
      possibly on multiple clinical information systems. This paper describes a model
      that defines the patient system of record and its constituent paper elements and
      electronic components. The model has been adopted by a large academic health
      science center for their development of an electronic patient record. The model
      has clarified which systems and data constitute the patient system of record and
      the standards and policies that apply to these systems.

PMID- 9929219
TI  - Methodology for security development of an electronic prescription system.
AB  - Data security is an essential requirement in all health care applications.
      Developers of medical information systems should utilize the existing security
      development and evaluation methods to foresee as many of the technical and human
      factors that may endanger data security as possible and apply appropriate
      precautions. Modern smart card technology facilitates the building of robust
      security framework for interorganizational shared care systems. In this article,
      we describe the way we utilized the existing security evaluation criteria in
      developing the security concept of our electronic prescription system.

PMID- 9929220
TI  - CATCH/IT: a data warehouse to support comprehensive assessment for tracking
      community health.
AB  - A systematic methodology, Comprehensive Assessment for Tracking Community Health
      (CATCH), for analyzing the health status of communities has been under
      development at the University of South Florida since the early 1990s. CATCH draws
      226 health status indicators from multiple data sources and uses an innovative
      comparative framework and weighted evaluation criteria to produce a rank-ordered
      list of community health problems. CATCH has been applied successfully in many
      Florida counties; focusing attention on high priority health issues and measuring
      the impact of health expenditures on community health status outcomes. Previously
      performed manually, we are using information technology (IT) to automate the
      CATCH methodology with a full-scale data warehouse, user-friendly forms and
      reports, and extended analysis and data mining capabilities. The automated
      system, CATCH/IT, will reduce the time to prepare community health status reports
      from months to days. In this paper, we present the current status of the project,
      along with the principal research and development issues and future directions of
      the project.

PMID- 9929222
TI  - Physician use of an ambulatory medical record system: matching form and function.
AB  - An ambulatory medical record system was implemented as a pilot project to
      determine the clinical and operational impacts of using interactive, computer
      based systems in the outpatient setting. Of the 58 physicians who attempted to
      use the AMR system, 28 continue as active users. Physicians who discontinued use
      of the system reported a variety of reasons for their dissatisfaction. As a
      result of the pilot, the AMR implementation team and physicians understand better
      how to fit the AMR system to a physician's specific requirements, as well as
      enhance the operation of the physician's practice. Armed with the experience
      gained during the early phases of the implementation, the Cleveland Clinic
      Foundation now intends a cautious expansion and continued evaluation of the AMR
      system, with the objective of meeting organizational needs with appropriate
      technical functions.

PMID- 9929221
TI  - Evaluation of online documentation.
AB  - The University of Iowa Hospitals and Clinics (UIHC) implemented an online
      documentation system for patient care orders in 1994-1996. Developed entirely in
      house, the INFORMM NIS (Information Network for Online Retrieval & Medical
      Management Nursing Information System) features order-generated task lists,
      defaulted charting responses, computer-generated chart forms, and graphical data
      displays. To measure the impact of automation on user perceptions, and
      documentation compliance, completeness, time, and location, a team of nursing and
      information systems representatives captured data before and after
      implementation. Staff surveys show more positive user perceptions. Documentation
      results indicate increased compliance and completeness, and a decrease or no
      change in time. Online documentation occurs mainly at unit workstations.

PMID- 9929223
TI  - Automated key process monitors for patient care documentation.
AB  - Complete, accurate and timely patient care documentation is an essential part of
      the practice of medicine. As with any other process in medicine or industry,
      continuous quality improvement (CQI) is essential to assure the highest quality
      at the lowest cost. CQI requires objective key process measures that can be
      assessed routinely. A set of key process monitors designed to assess
      completeness, accuracy and timeliness were created based on local, regional and
      national standards. Feasibility was assessed in the LDS Hospital Emergency
      Department using 31,429 patient visits in the 18 months from June 1995 to
      November 1996. The logic of the score was programmed into SQL scripts and run
      against an Oracle database containing the patient care documentation. The results
      indicate that the chosen key process monitors can be used to provide real time
      assessment of the patient care documentation process. The general concepts of the
      key process measures of completeness, accuracy and timeliness are generalizable
      to many areas of medicine. The overall score provides one method of easily
      tracking departmental performance while the overall process monitoring database
      allows powerful, in-depth analysis of individual components of the process. It is
      recommended that such automated process monitoring tools be integrated into
      future clinical information systems.

PMID- 9929224
TI  - Process modelling and simulation for managing clinical care in the community.
AB  - 'Care in the Community' is an easy catch phrase but a difficult goal. It is a
      phrase that addresses a current growth area within health care, and one that
      comes complete with an impressive array of political, economic and social factors
      that would seem to support the notion of a continuing trend. Technology,
      specifically information systems, however, has not been successfully cast in a
      supporting role. There are many reasons for this lack of success but a major one
      is the mismatch between the understanding of what is required to support the
      clinical care processes and the specifications of the current systems supplied.
      Specifically the interest here is in the use and assessment of two computer
      science techniques, i.e. process modelling and simulation, as suitable means of
      capturing and communicating requirements so as to bridge the divided and power
      differential between users and developers of information systems.

PMID- 9929225
TI  - Extracting medical knowledge for a coded problem list vocabulary from the UMLS
      Knowledge Sources.
AB  - INTRODUCTION: The Unified Medical Language System (UMLS) Knowledge Sources embody
      a rich source of medical knowledge. We sought to extract a portion of this
      knowledge by incorporating information about relationships between UMLS concepts
      into an existing problem list vocabulary. METHODS: We matched terms from the
      coded problem list of The Medical Record (TMR), a computer-based patient record
      system, with those found in the UMLS Metathesaurus. Those UMLS concepts that
      participate in 'parent' relationships with the matched TMR concepts were
      translated back into TMR codes and the relationship information was retained for
      integration into the coded problem list of TMR. RESULTS: Of the coded problems
      currently in use in TMR, 67% (1627/2436) could be matched by normalized string
      matches to the UMLS Knowledge Sources. Of these matched TMR concepts, 91%
      (1488/1627) participated in at least one UMLS-identified parent relationship but
      only 28% of the matched concepts (454/1627) participated in parent relationships
      that already matched to a TMR code. As a result, although 67% of TMR codes were
      matched to UMLS concepts, only 19% of our original problem list (454/2436) could
      be augmented by relationship information contained in UMLS without improving the
      rate of matches or adding additional UMLS concepts as coded problems in TMR.
      CONCLUSION: This study illustrates the rapid decline in overall rates of matching
      that result from a multiplicative effect of successive matches of terms to
      concepts, concepts to relationships and concepts back to entry terms. This effect
      will hamper any effort to extract relationship knowledge from the UMLS for
      incorporation into an entry vocabulary that is not already one of the source
      vocabularies of the UMLS Metathesaurus.

PMID- 9929226
TI  - Just-in-time coding of the problem list in a clinical environment.
AB  - Clinically useful problem lists are essential to the CPR. Providing a terminology
      that is standardized and understood by all clinicians is a major challenge. UNMC
      has developed a lexicon to support their problem list. Using a just-in-time
      coding strategy, the lexicon is maintained and extended prospectively in a
      dynamic clinical environment. The terms in the lexicon are mapped to ICD-9-CM,
      NANDA, and SNOMED International classification schemes. Currently, the lexicon
      contains 12,000 terms. This process of development and maintenance of the lexicon
      is described.

PMID- 9929227
TI  - Strategies for problem list implementation in a complex clinical enterprise.
AB  - Although the Institute of Medicine states that a patient problem list should have
      a prominent place in the computer-based patient record, the design and function
      of the problem list is not a matter of universal agreement. Developer experience
      with implementation has been inconsistent, in part because of confusion on data
      standards, uncertain user acceptance of data entry, and minimal rewards for the
      clinician. I propose that necessary features of the problem list include: 1)
      clinical focus, 2) codification of problems, 3) support for problem resolution,
      4) historicity of problems, 5) support for multiple clinical views, 6)
      integration of maintenance functions with workflow, 7) support for administrative
      reporting, and 8) integration with useful clinical tools. I describe the
      strategies that we employed to meet these goals while implementing the problem
      list in a computerized patient record serving a large, complex clinical
      enterprise. I further report the successful achievement of those goals based upon
      audits six months after implementation.

PMID- 9929228
TI  - Modeling utilization of planned information technology.
AB  - The antecedents of technology use involve user, system, task and organization
      characteristics as well as externalities which can affect all of these entities.
      Evaluation of all entity attributes would be impossible; however, measurement of
      the interaction effects between these entities can act as a proxy for individual
      attribute values. A model is proposed which, based upon evaluation of these
      interaction effects, should predict technology utilization. This model will
      provide insight into the relationship between the antecedents of technology
      utilization. Also, application of the approach described can provide a predictive
      model and taxonomy of variables which can be applied to predict or manipulate the
      likelihood of utilization for planned technology.

PMID- 9929229
TI  - Computerized management of diabetes: a synthesis of controlled trials.
AB  - Computerized management of diabetes is the use of information technology to
      improve diabetic patient outcomes. The computer can be used to provide
      educational information to patients and facilitate the storage and transmittal of
      clinical data between patients and clinicians. The objective of this paper was to
      evaluate computerized management of diabetes in changing the health outcomes.
      Clinical trial reports were identified through systematic electronic database and
      manual searches. Four eligibility criteria were applied: diabetes clinical area;
      prospective, contemporaneously controlled clinical trial with random assignment
      of the intervention; computer generated information for patients in the
      intervention group and no similar intervention in the control group; and
      measurement of effect on the outcome of care (health status, social functioning,
      patient/family satisfaction). Data were abstracted using a standardized
      abstraction form and the quality of methodology was scored. Of 15 eligible
      clinical trials, 12 (80%) reported positive outcomes or significant benefits. A
      total of 48 outcome measures were reported, an average of 3.2/study.
      Significantly improved clinical outcomes included Hemoglobin A1c (HbA1c), blood
      glucose, and hypoglycemic events. Patient-computer interaction appears to be a
      valuable supplement to interaction with clinicians. Considering the need to
      enhance patient participation in the care of chronic illnesses, initial evidence
      indicates computers can play a more significant role in the future.

PMID- 9929230
TI  - "Virtual" clinical trials: case control experiments utilizing a health services
      research workstation.
AB  - We created an interface to a growing repository of clinical and administrative
      information to facilitate the design and execution of case-control experiments.
      The system enables knowledgeable users to generate and test hypotheses regarding
      associations among diseases and outcomes. The intuitive interface allows the user
      to specify criteria for selecting cases and defining putative risks. The
      repository contains comprehensive administrative and selected clinical
      information on all ambulatory and emergency department visits as well as hospital
      admissions since 1994. We tested the workstation's ability to determine
      relationships between outpatient diagnoses including hypertension, osteoarthritis
      and hypercholesterolemia with the occurrence of admissions for stroke and
      myocardial infarction and achieved results consistent with published studies.
      Successful implementation of this Health Services Research Workstation will allow
      "virtual" clinical trials to validate the results of formal clinical trials on a
      local population and may provide meaningful analyses of data when formal clinical
      trials are not feasible.

PMID- 9929231
TI  - Representing the work of medical protocols for organizational simulation.
AB  - Developing and implementing patient care protocols within a specific
      organizational setting requires knowledge of the protocol, the organization, and
      the way in which the organization does its work. Computer-based simulation tools
      have been used in many industries to provide managers with prospective insight
      into problems of work process and organization design mismatch. Many of these
      simulation tools are designed for well-understood routine work processes in which
      there are few contingent tasks. In this paper, we describe theoretic that make it
      possible to simulate medical protocols using an information-processing theory
      framework. These simulations will allow medical administrators to test different
      protocol and organizational designs before actually using them within a
      particular clinical setting.

PMID- 9929232
TI  - Linking information needs with evaluation: the role of task identification.
AB  - Action Identification Theory was used to explore user's subjective constructions
      of information tasks in a primary care setting. The first part of the study
      involved collecting clinician's descriptions of their information tasks. These
      items were collated and then rated by another larger group of clinicians. Results
      clearly identified 6 major information tasks, including communication, patient
      assessment, work monitoring, seeking science information, compliance with
      policies and procedures, and data integration. Results discussed in terms of
      implications for evaluation and assessing information needs in a clinical
      setting.

PMID- 9929233
TI  - Modifiable templates facilitate customization of physician order entry.
AB  - Physician order entry is a key factor in improving the quality of healthcare,
      while simultaneously reducing its cost. This paper describes an editor, a
      database, and a run-time system for creating and executing highly customized,
      user modifiable, order entry templates. The system allows non-programmers to
      create new order entry templates rapidly. Over the past 18 months, the templates
      have been used on over 2500 patients to enter over 40,000 separate orders.

PMID- 9929234
TI  - Clinical application of the UMLS in a computerized order entry and decision
      support system.
AB  - Vanderbilt University Medical Center uses the UMLS as a dictionary, an
      interlingua, and a knowledge source within the WizOrder system. WizOrder provides
      direct care-provider order entry and integrated clinical decision-support
      capabilities. Linking the two functions enables efficient decision-support during
      the "normal" workflow of care providers, at the point where decisions are made.
      WizOrder uses the UMLS as a dictionary to encode free-text entries into
      controlled vocabularies such as ICD9. As an interlingua, the UMLS provides
      mapping between vocabularies, allowing to translate patient-specific information
      to MeSH terms and perform automated literature retrieval. WizOrder uses the
      tables of co-occurring concepts and the Semantic Network to provide sensible
      lists of potential drug interactions and adverse drug reactions, and generate
      fully-formed MEDLINE queries for PubMed.

PMID- 9929235
TI  - Problem focused knowledge navigation: implementing the problem focused medical
      record and the O-HEAP note.
AB  - The current organization of most Computerized Medical Records (CMR) is based on
      the Problem Oriented Medical Record (POMR) and the SOAP (Subjective, Objective,
      Assessment and Plan) note. The organizational structure of the POMR and
      especially the SOAP note, does not allow for optimal use of computer capabilities
      in the follow up note. Since follow up visits are the most common office visit by
      far, this is a major flaw in the CMR. The authors propose a Problem Focused
      Medical Record and the OHEAP (Orientation, History, Exam, Assessment and Plan)
      note to resolve this problem. OHEAP starts with a powerful orientation structure
      that brings forward the timeline, last Assessment and Plan, and Plan Results for
      each problem along with the patient's historical tables as the starting point of
      every follow up visit. The Assessment and Plan portion brings problem specific
      differential diagnoses and their workups along with other relevant tables such as
      expert systems, treatments, instructions, medical literature or pathways. This
      leads to Problem Focused Knowledge Navigation that brings powerful efficiencies
      to the CMR. By recognizing the true workflow in the longitudinal diagnosis and
      management of any medical problem, the efficiency of the CMR is maximized. OHEAP
      allows for optimal use of both personal and external data elements in the medical
      record. Its powerful orientation attributes minimize the time spent in analyzing
      the current status of the problem while its connections to problem specific
      databases help resolve the problem.

PMID- 9929236
TI  - Implementation of an on-line Emergency Unit nursing system.
AB  - We designed and implemented an Emergency Unit nursing system which has been in
      practice since March of 1995. The system has been very successful and is used on
      97% of all Emergency Unit visits. The system is designed for rapid entry and
      retrieval of information. We have found that the time spent by nurses documenting
      patient care in this system is minimal. On average, over a six day study period
      only five minutes per patient visit, and about 30 minutes per nurse per shift was
      spent actually entering information into the system. We plan to continue to
      evaluate the use of the system and expand it to include use by other disciplines
      in the near future.

PMID- 9929237
TI  - Patients' acceptance of Internet-based home asthma telemonitoring.
AB  - We studied asthma patients from a low-income inner-city community without
      previous computer experience. The patients were given portable spirometers to
      perform spirometry tests and palmtop computers to enter symptoms in a diary, to
      exchange messages with physician and to review test results. The self-testing was
      performed at home on a daily basis. The results were transmitted to the hospital
      information system immediately after completion of each test. Physician could
      review results using an Internet Web browser from any location. A constantly
      active decision support server monitored all data traffic and dispatched alerts
      when certain clinical conditions were met. Seventeen patients, out of 19 invited,
      agreed to participate in the study and have been monitored for three weeks. They
      have been surveyed then using standardized questionnaire. Most of the patients
      (82.4%) characterized self-testing procedures as "not complicated at all." In
      70.6% of cases self-testing did not interfere with usual activities, and 82.4% of
      patients felt the self-testing required a "very little" amount of their time. All
      patients stated that it is important for them to know that the results can be
      reviewed by professional staff in a timely manner. However, only 29.5% of
      patients reviewed their results at least once a week at home independently. The
      majority of the patients (94.1%) were strongly interested in using home asthma
      telemonitoring in the future. We concluded that Internet-based home asthma
      telemonitoring can be successfully implemented in the group of patients without
      previous computer background.

PMID- 9929238
TI  - Creation and maintenance of Helix, a Web based database of medical genetics
      laboratories, to serve the needs of the genetics community.
AB  - Helix (healthlinks.washington.edu/helix) is a web accessible database that serves
      as the main U.S. directory of laboratories offering genetic testing. The database
      was designed to address the previously unmet need for a centralized, continuously
      updated source of information about clinical and research genetic testing to keep
      pace with the rapid rate of gene discovery resulting from the Human Genome
      Project. The Helix project began in 1992 at the University of Washington and
      Children's Hospital and Regional Medical Center. It has evolved from a single
      user stand alone relational database to a fully Web enabled database queried and
      maintained via the web and linked to other web accessible genomic databases. As
      of February, 1998 it lists more than 500 diseases and 290 laboratories, with over
      5,200 registered users making approximately 250 queries/day (90% via the
      Internet). We describe the iterative design, implementation, population and
      assessment of the database over a six year period.

PMID- 9929239
TI  - Nationwide telecare for diabetics: a pilot implementation of the HOLON
      architecture.
AB  - This paper presents results from a demonstration project of nationwide exchange
      of health data for the home care of diabetic patients. A consortium of industry,
      academic, and health care partners has developed reusable middleware components
      integrated using the HOLON architecture. Engineering approaches for multi
      organization systems development, lessons learned in developing layered object
      oriented systems, security and confidentiality considerations, and functionality
      for nationwide telemedicine applications are discussed.

PMID- 9929240
TI  - Baby CareLink: development and implementation of a WWW-based system for neonatal
      home telemedicine.
AB  - Baby CareLink is a multifaceted telemedicine application designed to provide
      individualized information and support to families of Very Low Birth Weight
      infants. We believe that this innovative use of WWW and telemedicine technologies
      will improve family satisfaction and clinical care. In conjunction with
      improvements in family involvement, discharge planning, education, and follow-up
      enabled by other CareLink components, this system may allow infants to transition
      home even earlier in their hospital stay and thereby provide a clear cost
      savings. This paper discusses the CareLink architecture and lessons learned in
      implementing a telemedicine link with families at home from an in-hospital
      clinical unit.

PMID- 9929241
TI  - Health information identification and de-identification toolkit.

PMID- 9929243
TI  - Protecting clinical data on Web client computers: the PCASSO approach.
AB  - The ubiquity and ease of use of the Web have made it an increasingly popular
      medium for communication of health-related information. Web interfaces to
      commercially available clinical information systems are now available or under
      development by most major vendors. To the extent that such interfaces involve the
      use of unprotected operating systems, they are vulnerable to security limitations
      of Web client software environments. The Patient Centered Access to Secure
      Systems Online (PCASSO) project extends the protections for person-identifiable
      health data on Web client computers. PCASSO uses several approaches, including
      physical protection of authentication information, execution containment,
      graphical displays, and monitoring the client system for intrusions and co
      existing programs that may compromise security.

PMID- 9929242
TI  - Vital signs services for secure telemedicine applications.
AB  - Telemedicine using teleconference provides only a part of the picture. The remote
      patient's electronic medical record and vital signs may often be essential for
      proper diagnosis and treatment. While there are commercial solutions for
      telemonitoring, they do not address issues such as security and interoperability
      leveraging the growing public communications infrastructure. On the other hand
      there are performance considerations due to the quality of service over available
      communications media that can hinder real-time operation. The objective of this
      research effort is to develop secure tele-monitoring facilities that enable
      healthcare providers to collaborate over public communication networks; to
      securely convey their patient's vital signs to a remote specialist; and to enable
      "near real-time" examination of those vital sign data. It is our belief that such
      applications can help overcome barriers to quality healthcare in the scattered
      populations of rural areas enabling telemedicine to be a part of the practice of
      medicine. The authors, who are developing secure telemedicine applications,
      describe their approach in developing secure vital signs services.

PMID- 9929244
TI  - Implementation of organizational practices to protect information in health
      organizations.
AB  - In March of 1997, the National Research Council (NRC) of the National Academy of
      Sciences issued the report, "For the Record: Protecting Electronic Health
      Information." In its report, the Council recommended both technical and
      organizational practices to protect electronic health information. At the time
      the report was issued, Vanderbilt University Medical Center was deeply immersed
      in the development of organizational practices consistent with the Council's
      recommendations. We agreed that the recommended technical and organizational
      practices are important for protecting other information types in addition to
      health information, and that they suggest appropriate practices for non
      electronic information, as well. In this paper, we focus on our process for
      developing and implementing the seven organizational practices recommended for
      immediate implementation.

PMID- 9929245
TI  - Extending contemporary decision support system designs to patient-oriented
      systems.
AB  - Decision support systems for patients can benefit from adopting knowledge
      engineering-based architectures. In this paper, we describe how decision support
      systems for patients differ from decision support systems for health
      professionals and knowledge engineering principles that can be used to improve
      the efficiency of developing patient support systems. We discuss a five-step
      process model for patient-computer dialogue and its incorporation into an
      architecture based on knowledge engineering ontologies. The architecture's
      components are grouped into transient and persistent application layers that
      support a general framework for patient decision support. The implementation of
      the object-based model using a relational database management system is also
      discussed.

PMID- 9929246
TI  - Designing HeartCare: custom computerized home care for patients recovering from
      CABG surgery.
AB  - With the current trend toward discharge of cardiac artery bypass graft (CABG)
      patients from the hospital after 5 days, clinicians must make effective use of
      existing computer technology to provide more efficiently the services once
      available during the patient's lengthier hospital stay. This paper describes the
      design of the HeartCare initiative, a computerized cardiac recovery service
      designed to provide home-care support for patients in the first three months
      following CABG surgery. Capitalizing on the expansion in health resources on the
      Internet, and building on the lessons from the ComputerLink projects, HeartCare
      will employ the World Wide Web platform in the generation of personalized in-home
      computerized access to recovery resources. Key implementation decisions include
      selection of WebTV/ as the home-based device, and application of Metadata to
      organizing health-related knowledge resources on the WWW.

PMID- 9929247
TI  - CARE-PARTNER: a computerized knowledge-support system for stem-cell post
      transplant long-term follow-up on the World-Wide-Web.
AB  - Evidence-based practice in medicine promotes the performance of medicine based
      upon proven and validated practice. The CARE-PARTNER system presented here is a
      computerized knowledge-support system for stem-cell post-transplant long-term
      follow-up (LTFU) care on the WWW, which means that it monitors the quality of the
      knowledge both of its own knowledge-base and of its users. Its aim is to support
      the evidence-based practice of the LTFU clinicians and of the home-town
      physicians who actually care for the transplanted patients. Currently, three
      fundamental characteristics of CARE-PARTNER are accountable for its knowledge
      support function: the quality of its knowledge-base, its availability on the WWW,
      and its learning from experience capability. As a matter of fact, the integration
      of a case-based reasoner in the reasoning framework enables the system to
      introspectively study its results, and to learn from its successes and failures,
      thus confronting the quality of the guidelines and pathways it reuses to the
      reality and complexity of the clinical cases.

PMID- 9929249
TI  - Remote clinical assessment for acute trauma: an initial experience.
AB  - Optimal care of the injured patient requires an organized approach, dedicated
      resources and clinical expertise. Victims of major trauma, however, frequently
      present to rural and suburban hospitals regardless of whether a dedicated trauma
      system in place. Immediate consultation by a trauma expert could potentially
      expedite effective evaluation and management of trauma victims, reducing the
      occurrence of unnecessary transport and leading to efficient stabilization and
      transport when needed. Remote assessment of trauma patients must be assesses for
      feasibility, safety and efficacy before widespread implementation. This project
      represents the initial steps towards the development of a functional telemedicine
      system for trauma care.

PMID- 9929248
TI  - Linking multiple heterogeneous data sources to practice guidelines.
AB  - The BiliLIGHT system is a World Wide Web (Web) based system that integrates an
      interactive clinical practice guideline with real-time patient-data retrieval
      from remote heterogeneous data sources to help clinicians manage newborn jaundice
      at the point of care in three clinical settings. We briefly describe the system,
      how actual information exchange of medical data across institutional boundaries
      was achieved, and how the data were connected to a CPG. In particular, we examine
      the requirements for patient identification, exchange protocols, authentication,
      and a standard vocabulary.

PMID- 9929251
TI  - HOLON: extending Web document libraries via objects in order to support the
      health information infrastructure. Health Object Library Online.
AB  - In HOLON, user clients, applications, data servers, and fine-grained elements are
      all objects in a document library. To that end, this paper reviews the past year
      of progress and lessons learned in HOLON for integrating the Web, HL7, CORBA,
      Arden, KQML, UMLS Thesaurus, and other standards to determine if object
      technology reduces common problems in document-centric libraries such as
      indexing, searching/retrieving, complex data type management, and maintenance,
      among others.

PMID- 9929250
TI  - Managing care in an integrated delivery system via an Intranet.
AB  - The CareGroup Provider Service Network is a managed care contracting organization
      which provides central administrative services for over 1800 physicians and
      200,000 managed care lives. Services include utilization management, disease
      management and credentialing for the entire network. The management model of the
      Provider Service Network empowers local physician groups with information and
      education. To meet the managed care information needs of the network, we
      implemented an intranet-based executive information system, PSNWeb, which
      retrieves data from a managed care data warehouse. The project required the
      integration of diverse technologies and development of a complex
      security/confidentiality infrastructure to deliver information to 8 major
      clinician groups, each with different information needs.

PMID- 9929252
TI  - A component-based problem list subsystem for the HOLON testbed. Health Object
      Library Online.
AB  - One of the deliverables of the HOLON (Health Object Library Online) project is
      the specification of a reference architecture for clinical information systems
      that facilitates the development of a variety of discrete, reusable software
      components. One of the challenges facing the HOLON consortium is determining what
      kinds of components can be made available in a library for developers of clinical
      information systems. To further explore the use of component architectures in the
      development of reusable clinical subsystems, we have incorporated ongoing work in
      the development of enterprise terminology services into a Problem List subsystem
      for the HOLON testbed. We have successfully implemented a set of components using
      CORBA (Common Object Request Broker Architecture) and Java distributed object
      technologies that provide a functional problem list application and UMLS-based
      "Problem Picker." Through this development, we have overcome a variety of
      obstacles characteristic of rapidly emerging technologies, and have identified
      architectural issues necessary to scale these components for use and reuse within
      an enterprise clinical information system.

PMID- 9929253
TI  - Delivering labeled teaching images over the Web.
AB  - The Web provides educators with the best opportunity to date for distributing
      teaching images across the educational enterprise and within the clinical
      environment. Experience in the pre-Web era showed that labels and information
      linked to parts of the image are crucial to student learning. Standard Web
      technology does not enable the delivery of labeled images. We have developed an
      environment called OverLayer that succeeds in the authoring and delivering of
      such images in a variety of formats. OverLayer has a number of functional
      specifications, based on the literature and on our experience, among them, the
      following: Users should be able to find components by name or by image; to
      receive feedback about their choice to test themselves. The image should be of
      arbitrary size; should be reusable; should be linked to further information;
      should be stand-alone files. The labels should not obscure the image; should be
      linked to further information. Images should be stand-alone files that can be
      transferred among faculty members. Implemented in Java, OverLayer
      (http:/(/)omie.med.jhmi.edu/overlayer) has at its heart a set of object classes
      that have been reused in a number of applets for different teaching purposes and
      a file format for creating OverLayer images. We have created a 350-image
      histology library and a 500-image pathology library, and are working on a 400
      image GI endoscopy library. We hope that the OverLayer suite of classes and
      implementations will help to further the gains made by previous image-based
      hyperlinked technologies.

PMID- 9929254
TI  - The digital anatomist structural abstraction: a scheme for the spatial
      description of anatomical entities.
AB  - In this paper, we propose a generalized scheme for the symbolic description of
      the spatial attributes of anatomical entities. The power of the scheme lies in
      the ability to model the spatial objects at the highest level of granularity:
      information can be obtained at the desired level of detail needed for a given
      application. This scheme uses the topological classes of point, line, surface,
      and volume to represent zero-D, one-D, two-D and three-D objects. A spatial
      object participates as a node in three complementary networks; the topology
      network, the part-of network, and the spatial associations network. The topology
      network describes a spatial object in terms of its boundaries, the part-of
      network describes a spatial object in terms of its parts, and the spatial
      associations network describes the spatial object in terms of its relationships
      to other spatial objects. All three of the networks can be used in combination or
      alone to answer queries to the spatial information system. The Digital Anatomist
      Structural Abstraction together with the other components of the Digital
      Anatomist Foundational Model will provide the information for describing and
      reasoning about anatomical entities.

PMID- 9929255
TI  - Identification of anatomical terminology in medical text.
AB  - We report on an experiment to use the natural language processing tools being
      developed in the SPECIALIST system to accurately identify terminology associated
      with the coronary arteries as expressed in coronary catheterization reports. The
      ultimate goal is to map from any anatomically-oriented medical text to online
      images, using the UMLS as an intermediate knowledge source. We describe some of
      the problems encountered when processing coronary artery terminology and report
      on the results of a formative evaluation of a tool for addressing these problems.

PMID- 9929256
TI  - Partonomies for interactive explorable 3D-models of anatomy.
AB  - We introduce a concept to model subtle part-whole-semantics for the use with
      interactive 3d-models of human anatomy. Similar to experiences with modeling
      partonomies for physical artifacts like machines or buildings we found one unique
      part-whole-relation to be insufficient to represent anatomical reality. This
      claim will be illustrated with anatomical examples. According to the requirements
      these examples demand, a semantic classification of part-whole-relations is
      introduced. Initial results in modeling anatomical partonomies for a 3d
      visualization environment proved this approach to be an promising way to
      represent anatomy and to enable powerful complex inferences.

PMID- 9929257
TI  - Simulating patients with Parallel Health State Networks.
AB  - The American Board of Family Practice is developing a computer-based
      recertification process to generate patient simulations from a knowledge base.
      Simulated patients require a stochastically generated history and response to
      treatment, suggesting a Monte Carlo-like patient generation process. Knowledge
      acquisition experiments revealed that description of a patient's overall health
      as a node in a Monte Carlo model was difficult for domain experts to use,
      severely limited knowledge reusability, and created a plethora of awkwardly
      defined health states. We explored a model in which patients traverse several
      parallel health state networks simultaneously, so that overall health is a vector
      describing the current nodes from every Parallel Network. This model has a
      reasonable biological basis, more easily defined data, and greatly improved reuse
      potential, at the cost of more complex simulation algorithms. Experiments using
      osteoarthritis stages, weight classification, and absence or presence of gastric
      ulcers as three Parallel Networks demonstrate the feasibility of this approach to
      simulating patients.

PMID- 9929258
TI  - A qualitative model for computer-assisted instruction in cardiology.
AB  - CARDIOLAB is an interactive computational framework dedicated to teaching and
      computer-aided diagnosis in cardiology. The framework embodies models that
      simulate the heart's electrical activity. They constitute the core of a Computer
      Assisted Instruction (CAI) program intended to teach, in a multimedia
      environment, the concepts underlying rhythmic disorders and cardiac diseases. The
      framework includes a qualitative model (QM) which is described in this paper.
      During simulation using QM, dynamic sequences representing impulse formation and
      conduction processes are produced along with the corresponding qualitative
      descriptions. The corresponding electrocardiogram (ECG) and ladder diagram are
      also produced, and thus, both qualitative notions and quantitative facts can be
      taught via the model. We discuss how qualitative models in particular, and
      computational models in general can enhance the teaching capability of CAI
      programs.

PMID- 9929259
TI  - Improving patient outcomes by including patient preferences in nursing care.
AB  - While preference elicitation techniques have been effective in supporting
      patients in their abilities to make decisions consistent with their preferences,
      little is known about whether information about patient preferences affects
      clinicians in clinical decision making and improves patient outcomes. This paper
      presents a study that tested the effect of eliciting elderly patients'
      preferences for self-care capability and providing this information to nurses in
      clinical practice on nurses' care priorities and patient outcomes. The study
      showed that information about patient preferences changed nurses' care priorities
      to be more consistent with patient preferences and improved patient outcomes of
      preference achievement and physical functioning. These results emphasize the
      importance of continuing to refine strategies for eliciting and integrating
      patient preferences into patient care as a means to improve patient outcomes.

PMID- 9929260
TI  - Child health records: are they valid and useful to children and pediatric
      practitioners?
AB  - Children are important consumers of health care, yet neither children nor their
      clinical practitioners have received much attention from the health informatics
      community. Child health needs differ from those of adults, and the purpose of
      health encounters for children focus to a greater extent on health promotion and
      evaluation of developmental milestones. The early childhood period is critical
      because it is during this time the children develop the expectations and
      attitudes about health care that they will carry with them throughout their
      lives. The primary purpose of this project is to examine the congruence in
      communication between children and pediatric practitioners. From this examination
      implications will be drawn for designing pediatric clinical records and
      developing strategies for determining the extent to which the record serve the
      child's health information needs and the clinician's health service delivery
      needs.

PMID- 9929261
TI  - A vertical curriculum to teach the knowledge, skills, and attitudes of medical
      informatics.
AB  - It is becoming increasingly apparent that medical schools must begin teaching the
      knowledge, skills and attitudes of information literacy and applied medical
      informatics as core competencies in undergraduate medical education. The
      University of Vermont College of Medicine recognized that these core competencies
      were lacking in its curriculum, and in 1992 it implemented a four year,
      integrated program to give students the information habits essential to twenty
      first century practice. The first graduates of the program are now in residencies
      and feedback has enabled the College to refine the program to better meet the
      informatics education needs of the next generation of physicians. The result of
      these efforts is the Vertical Curriculum in Information Literacy and Applied
      Medical Informatics; its process of development, the product of the process, and
      its outcomes are discussed.

PMID- 9929262
TI  - The dependence of educational infrastructure on clinical infrastructure.
AB  - The Albert Einstein College of Medicine needed to assess the growth of its
      infrastructure for educational computing as a first step to determining if
      student needs were being met. Included in computing infrastructure are space,
      equipment, software, and computing services. The infrastructure was assessed by
      reviewing purchasing and support logs for a six year period from 1992 to 1998.
      This included equipment, software, and e-mail accounts provided to students and
      to faculty for educational purposes. Student space has grown at a constant rate
      (averaging 14% increase each year respectively). Student equipment on campus has
      grown by a constant amount each year (average 8.3 computers each year). Student
      infrastructure off campus and educational support of faculty has not kept pace.
      It has either declined or remained level over the six year period. The
      availability of electronic mail clearly demonstrates this with accounts being
      used by 99% of students, 78% of Basic Science Course Leaders, 38% of Clerkship
      Directors, 18% of Clerkship Site Directors, and 8% of Clinical Elective
      Directors. The collection of the initial descriptive infrastructure data has
      revealed problems that may generalize to other medical schools. The discrepancy
      between infrastructure available to students and faculty on campus and students
      and faculty off campus creates a setting where students perceive a paradoxical
      declining support for computer use as they progress through medical school. While
      clinical infrastructure may be growing, it is at the expense of educational
      infrastructure at affiliate hospitals.

PMID- 9929263
TI  - An overview of the medical informatics curriculum in medical schools.
AB  - As medical schools incorporate medical informatics into their curriculum the
      problems of implementation arise. Because there are no standards regarding a
      medical informatics curriculum, medical schools are implementing the subjects in
      various ways. A survey was undertaken to amass an overview of the medical
      informatics curriculum nationally. Of the responding schools, most have aspects
      of medical informatics incorporated into current courses and utilize existing
      faculty. Literature searching, clinical decision-making, and Internet are the
      basic topics in the current curricula. The trend is for medical informatics to be
      incorporated throughout all four years of medical school. Barriers are the
      difficulties in faculty training, and slow implementation.

PMID- 9929264
TI  - Public health informatics: a CDC course for public health program managers.
AB  - Information science and technology are critical to the modern practice of public
      health. Yet today's public health professionals generally have no formal training
      in public health informatics--the application of information science and
      technology to public health practice and research. Responding to this need, the
      U.S. Centers for Disease Control and Prevention (CDC) recently developed, tested,
      and delivered a new training course in public health informatics. The course was
      designed for experienced public health program managers and included sessions on
      general informatics principles and concepts; key information systems issues and
      information technologies; and management issues as they relate to information
      technology projects. This course has been enthusiastically received both at the
      state and federal levels. We plan to develop an abbreviated version for health
      officers, administrators, and other public health executives.

PMID- 9929265
TI  - P-CAPE: a high-level tool for entering and processing clinical practice
      guidelines. Partners Computerized Algorithm and Editor.
AB  - The Partners Computerized Algorithm Processor and Editor (P-CAPE) is a high-level
      tool intended to remove the programming bottleneck for implementing practice
      guidelines in our computer-based record system, and to integrate guideline-based
      advice into the clinician's workflow. P-CAPE has three major components: 1) An
      Editor that allows an analyst to enter the parameters of a guideline in the form
      of an algorithm; 2) A Navigator that processes the steps of the guideline and
      logs all transactions in a patient-specific file; and 3) A clinician Notifier
      that sends messages to a patient's covering clinician, seeking data or presenting
      recommendations and order sets that can be processed by the system. P-CAPE's
      guideline object model was adapted from the InterMed Collaboratory GuideLine
      Interface Format (GLIF).

PMID- 9929266
TI  - Intention-based critiquing of guideline-oriented medical care.
AB  - We present a methodology and tool for providing retrospective review and
      critiquing of guideline-based medical care given to patients. We show how our
      guideline representation language, Asbru, which supports the use of physicians
      intentions in addition to physician's actions, allows us to compare the care
      given to a patient at the level of the intention to treat in addition to the more
      detailed plan carried out. We have developed an algorithm based on this
      representation for retrospective quality assessment of guideline-based care. Our
      method takes the physician's and institution's preferences and policies into
      account in explaining or justifying physician deviations from the recommendations
      of a guideline.

PMID- 9929267
TI  - Hypertextual navigation operationalizing generic clinical practice guidelines for
      patient-specific therapeutic decisions.
AB  - Despite the proliferation of implemented clinical practice guidelines, there is
      still little evidence of physicians compliance to formal standards. The ONCODOC
      project proposes a framework for elaborating generic decision support guidelines
      in a document-based paradigm with a knowledge-based approach. It has been first
      applied to assist clinicians in the treatment of breast cancer patients.
      Therapeutic expertise has been encoded as a decision tree. The decision process
      is driven by the clinician who interactively browses a hypertext version of the
      decision tree. During the navigation, he incrementally assigns values to decision
      parameters on the basis of his free interpretation of his patient's condition and
      thus builds a clinical context leading to patient-specific therapeutic
      recommendations. These guidelines are distributed on a hospital intranet and are
      evaluated at the point of care in an oncology department.

PMID- 9929268
TI  - Long-term changes in compliance with clinical guidelines through computer-based
      reminders.
AB  - We evaluate the effectiveness of computer-based reminders in improving compliance
      with preventive medicine screening guidelines and examine the long-term impact of
      these reminders. Physicians in an ambulatory care practice were given a summary
      health maintenance report of preventive screening items at each scheduled patient
      visit. The electronic medical record (COSTAR) in use in this practice was
      programmed to integrate 13 clinical guidelines into the routine flow of care.
      Mean performance of 10 out of 13 health maintenance measures improved in the year
      following introduction of the integrated guideline report (p less than .001 by
      chi-square test for 8 items, p less than .01 for 2 items). Five years after the
      report was introduced, improvement in mean performance persisted for 7 measures
      (p less than .001 by chi-square test), compliance improved for one additional
      measure (p less than .001), and improvement disappeared for three measures that
      had shown improvement in the first year of the intervention.

PMID- 9929269
TI  - Scaling an expert system data mart: more facilities in real-time.
AB  - Clinical Data Repositories are being rapidly adopted by large healthcare
      organizations as a method of centralizing and unifying clinical data currently
      stored in diverse and isolated information systems. Once stored in a clinical
      data repository, healthcare organizations seek to use this centralized data to
      store, analyze, interpret, and influence clinical care, quality and outcomes. A
      recent trend in the repository field has been the adoption of data marts-
      specialized subsets of enterprise-wide data taken from a larger repository
      designed specifically to answer highly focused questions. A data mart exploits
      the data stored in the repository, but can use unique structures or summary
      statistics generated specifically for an area of study. Thus, data marts benefit
      from the existence of a repository, are less general than a repository, but
      provide more effective and efficient support for an enterprise-wide data analysis
      task. In previous work, we described the use of batch processing for populating
      data marts directly from legacy systems. In this paper, we describe an
      architecture that uses both primary data sources and an evolving enterprise-wide
      clinical data repository to create real-time data sources for a clinical data
      mart to support highly specialized clinical expert systems.

PMID- 9929270
TI  - A graphical tool for ad hoc query generation.
AB  - Medical data are characterized by complex taxonomies and evolving terminology.
      Questions that clinicians, medical administrators, and researchers may wish to
      answer using medical databases are not easily formulated as SQL queries. In this
      paper we describe a graphical tool that facilitates formulation of ad hoc
      questions as SQL queries. This tool manages multiple attribute hierarchies and
      creates SQL query strings by navigating through the hierarchies. This interactive
      tool has been optimized using indexing to improve the overall speed of the query
      building and the data retrieval process. Indexed queries performed 5 to 100 times
      faster than query strings. However, query string generation time depends on the
      size of the taxonomies describing the hierarchies, while the index generation
      time depends on the size of the data warehouse.

PMID- 9929271
TI  - Large scale database scrubbing using object oriented software components.
AB  - Now that case managers, quality improvement teams, and researchers use medical
      databases extensively, the ability to share and disseminate such databases while
      maintaining patient confidentiality is paramount. A process called scrubbing
      addresses this problem by removing personally identifying information while
      keeping the integrity of the medical information intact. Scrubbing entire
      databases, containing multiple tables, requires that the implicit relationships
      between data elements in different tables of the database be maintained. To
      address this issue we developed DBScrub, a Java program that interfaces with any
      JDBC compliant database and scrubs the database while maintaining the implicit
      relationships within it. DBScrub uses a small number of highly configurable
      object-oriented software components to carry out the scrubbing. We describe the
      structure of these software components and how they maintain the implicit
      relationships within the database.

PMID- 9929272
TI  - Assessing an AI knowledge-base for asymptomatic liver diseases.
AB  - Discovering not yet seen knowledge from clinical data is of importance in the
      field of asymptomatic liver diseases. Avoidance of liver biopsy which is used as
      the ultimate confirmation of diagnosis by making the decision based on relevant
      laboratory findings only, would be considered an essential support. The system
      based on Quinlan's ID3 algorithm was simple and efficient in extracting the
      sought knowledge. Basic principles of applying the AI systems are therefore
      described and complemented with medical evaluation. Some of the diagnostic rules
      were found to be useful as decision algorithms i.e. they could be directly
      applied in clinical work and made a part of the knowledge-base of the Liver
      Guide, an automated decision support system.

PMID- 9929273
TI  - Guideline generation from data by induction of decision tables using a Bayesian
      network framework.
AB  - Decision tables can be used to represent practice guidelines effectively. In this
      study we adopt the powerful probabilistic framework of Bayesian Networks (BN) for
      the induction of decision tables. We discuss the simplest BN model, the Naive
      Bayes and extend it to the Two-Stage Naive Bayes. We show that reversal of edges
      in Naive Bayes and Two-stage Naive Bayes results in simple decision table and
      hierarchical decision table respectively. We induce these graphical models for
      dementia severity staging using the Clinical Dementia Rating Scale (CDRS)
      database from the University of California, Irvine, Alzheimer's Disease Research
      Center. These induced models capture the two-stage methodology clinicians use in
      computing the global CDR score by first computing the six category scores of
      memory, orientation, judgment and problem solving, community affairs, home and
      hobbies and personal care, and then the global CDRS. The induced Two-Stage models
      also attain a clinically acceptable performance when compared to domain experts
      and could serve as useful guidelines for dementia severity staging.

PMID- 9929274
TI  - Improving machine learning performance by removing redundant cases in medical
      data sets.
AB  - Neural network models and other machine learning methods have successfully been
      applied to several medical classification problems. These models can be
      periodically refined and retrained as new cases become available. Since training
      neural networks by backpropagation is time consuming, it is desirable that a
      minimum number of representative cases be kept in the training set (i.e.,
      redundant cases should be removed). The removal of redundant cases should be
      carefully monitored so that classification performance is not significantly
      affected. We made experiments on data removal on a data set of 700 patients
      suspected of having myocardial infarction and show that there is no statistical
      difference in classification performance (measured by the differences in areas
      under the ROC curve on two previously unknown sets of 553 and 500 cases) when as
      many as 86% of the cases are randomly removed. A proportional reduction in the
      amount of time required to train the neural network model is achieved.

PMID- 9929276
TI  - A comparison of neural network models for the prediction of the cost of care for
      acute coronary syndrome patients.
AB  - Acute coronary syndromes have remained the focus of many clinical economic
      studies due to the increasing prevalence of the disease and the tightening of
      cost controls. An accurate descriptive cost model for this population would be a
      valuable tool for clinical researchers. With such a model, the relative
      importance of different factors upon the total cost of care could be determined
      through computer simulation. This study explored the use of different neural
      network architectures in creating a descriptive cost model. This was a difficult
      problem in that the costs span 3 orders of magnitude but the output variable of
      the neural network must be restricted to the range 0-1. Models that used
      logarithmic transformations and multiple modular networks were created and
      analyzed. It was found that the model with a single network and logarithmic
      transformation performed significantly better than other more complicated
      networks.

PMID- 9929275
TI  - Comparison of multiple prediction models for ambulation following spinal cord
      injury.
AB  - Few studies have properly compared predictive performance of different models
      using the same medical data set. We developed and compared 3 models (logistic
      regression, neural networks, and rough sets) in the in prediction of ambulation
      at hospital discharge following spinal cord injury. We used the multi-center
      Spinal Cord Injury Model System database. All models performed well and had areas
      under the receiver operating characteristic curve in the 0.88-0.91 range. All
      models had sensitivity, specificity, and accuracy greater than 80% at ideal
      thresholds. The performance of neural network and logistic regression methods was
      not statistically different (p = 0.48). The rough sets classifier performed
      statistically worse than either the neural network or logistic regression models
      (p-values 0.002 and 0.015 respectively).

PMID- 9929277
TI  - Modeling treatment of ischemic heart disease with partially observable Markov
      decision processes.
AB  - Diagnosis of a disease and its treatment are not separate, one-shot activities.
      Instead they are very often dependent and interleaved over time, mostly due to
      uncertainty about the underlying disease, uncertainty associated with the
      response of a patient to the treatment and varying cost of different diagnostic
      (investigative) and treatment procedures. The framework of Partially observable
      Markov decision processes (POMDPs) developed and used in operations research,
      control theory and artificial intelligence communities is particularly suitable
      for modeling such a complex decision process. In the paper, we show how the POMDP
      framework could be used to model and solve the problem of the management of
      patients with ischemic heart disease, and point out modeling advantages of the
      framework over standard decision formalisms.

PMID- 9929278
TI  - Building manageable rough set classifiers.
AB  - An interesting aspect of techniques for data mining and knowledge discovery is
      their potential for generating hypotheses by discovering underlying relationships
      buried in the data. However, the set of possible hypotheses is often very large
      and the extracted models may become prohibitively complex. It is therefore
      typically desirable to only consider the "strongest" hypotheses, so that smaller
      models can be obtained that also retain good classificatory capabilities. This
      paper outlines how rule-based classifiers based on rough set theory and Boolean
      reasoning that are both small and perform well can be developed. Applied to a
      real-world medical dataset, the final models are shown to exhibit good
      performance using only a subset of the available information. Furthermore, the
      number of resulting rules is low and enables practical a posteriori inspection
      and interpretation of the models.

PMID- 9929279
TI  - Automated knowledge acquisition from clinical databases based on rough sets and
      attribute-oriented generalization.
AB  - Rule induction methods have been proposed in order to acquire knowledge
      automatically from databases. However, conventional approaches do not focus on
      the implementation of induced results into an expert system. In this paper, the
      author focuses not only on rule induction but also on its evaluation and presents
      a systematic approach from the former to the latter as follows. First, a rule
      induction system based on rough sets and attribute-oriented generalization is
      introduced and was applied to a database of congenital malformation to extract
      diagnostic rules. Then, by the use of the induced knowledge, an expert system
      which makes a differential diagnosis on congenital disorders is developed.
      Finally, this expert system was evaluated in an outpatient clinic, the results of
      which show that the system performs as well as a medical expert.

PMID- 9929280
TI  - New advances and validation of knowledge management tools for critical care using
      classifier techniques.
AB  - An earlier version (2.0) of the case-based reasoning (CBR) tool, called IDEAS for
      ICU's, allowed users to compare the ten closest matching cases to the newest
      patient admission, using a large database of intensive care patient records, and
      physician-selected matching-weights [1,2]. The new version incorporates matching
      weights, which have been determined quantitatively. A faster CBR matching engine
      has also been incorporated into the new CBR. In a second approach, a back
      propagation, feed-forward artificial neural network estimated two classes of the
      outcome "duration of artificial ventilation" for a subset of the database used
      for the CBR work. Weight-elimination was successfully applied to reduce the
      number of input variables and speed-up the estimation of outcomes. New
      experiments examined the impact of using a different number of input variables on
      the performance of the ANN, measured by correct classification rates (CCR) and
      the Average Squared Error (ASE).

PMID- 9929281
TI  - Evolution of a knowledge base for a clinical decision support system encoded in
      the Arden Syntax.
AB  - Clinical decision support systems (CDSS) are being used increasingly in medical
      practice. Thus, long-term maintenance of the knowledge bases (KB) of such systems
      becomes important. To quantify changes that occur as a KB evolves, we studied the
      KB at the Columbia-Presbyterian Medical Center. This KB has a total of 229
      Medical Logic Modules (MLMs) encoded in the Arden Syntax. Eliminating those never
      used in practice, we retrospectively analyzed 156 MLMs developed over 78 months.
      We noted 2020 distinct versions of these MLMs that included 5528 changed
      statements over time. These changes occurred primarily in the logic slot (38.7%
      of all changes), the action slot (17.8%), in queries (15.0%) and in the data slot
      exclusive of queries (12.4%). We conclude that long-term maintenance of a KB for
      a CDSS requires significant changes over time. We discuss the implications of
      these results for the design of KB editors for the Arden Syntax.

PMID- 9929282
TI  - Issues in accommodating national changes and local variation in a computer-based
      guideline for childhood immunization and in related knowledge maintenance tools.
AB  - As clinical practice guidelines are increasingly implemented in computer-based
      form, a major challenge will be to maintain their domain knowledge as new
      national recommendations are developed and as local customization is required.
      This maintenance may also need to be performed for any computer-based tools
      developed to help in the guideline knowledge maintenance process itself. This
      paper uses the domain of childhood immunization to explore certain issues
      involved. It describes 1) two recent changes to the national recommendations
      dealing with the DTP and Polio vaccine series, and 2) several customizations
      requested by the immunization registries of the State of Oregon and the US Indian
      Health Service. It then describes how these guideline practice variations are
      currently handled in three computer-based tools, IMM/Serve, IMM/Def, and
      IMM/Test. Finally, it discusses how the use of these tools can provide one
      approach to characterizing the complexity of guideline variations.

PMID- 9929283
TI  - Automated knowledge extraction from the UMLS.
AB  - This paper presents our work in extracting disease-chemical relationship
      knowledge from the UMLS Co-occurrence table (MRCOC) using an automated method. We
      evaluated the quality of the knowledge from UMLS MRCOC by comparing it with
      knowledge from other sources: For disease-lab chemical relationships, knowledge
      was obtained from a decision support system (DXplain) and our own knowledge base
      of medical terminology (MED) through automated processes. For disease-drug
      chemical relationships, knowledge was manually acquired from the medical
      literature. Evaluations showed that the UMLS MRCOC knowledge has good
      sensitivity, especially regarding disease-drug relationships. We are using this
      knowledge to produce disease-specific views of patients' electronic patient
      record.

PMID- 9929284
TI  - A computerized reminder for prophylaxis of deep vein thrombosis in surgical
      patients.
AB  - OBJECTIVE: To measure the effect of a computerized reminder system on the rate of
      deep vein thrombosis (DVT) prophylaxis in surgical patients. DESIGN: A
      prospective trial to measure change in compliance compared to historic controls.
      MEASUREMENTS: LDS Hospital surgeons developed local consensus as to which
      procedures should have DVT prophylaxis. The historic rate of prophylaxis for the
      procedures was measured through a database search of patient records. A
      computerized reminder system was then implemented which utilized an expert
      knowledge base and a time drive mechanism to flag surgical cases for DVT
      prophylaxis. For eligible patients, a DVT reminder appeared on the operating room
      schedule; surgical staff used this as a guide to apply prophylaxis. During the 3
      month trial the rate of DVT prophylaxis was remeasured and compared to the pre
      intervention rate. RESULTS: The pre-intervention rate of DVT prophylaxis over a 3
      month period was 85.2% (785 of 921 eligible cases). For the 3 months following
      the introduction of the computerized reminder, compliance with DVT prophylaxis
      increased to 99.3% (1084 of 1092 eligible cases). The difference between the
      historic controls and the study subjects was highly significant (p < 0.001).
      CONCLUSION: A computerized reminder is an effective method of increasing the rate
      of DVT prophylaxis in surgical patients.

PMID- 9929285
TI  - Can low accuracy disease risk predictor models improve health care using decision
      support systems?
AB  - A prototype decision support system has been designed for managing dental caries
      using a risk assessment model. Caries is a multifactorial disease with risk
      prediction models having low sensitivity (65%) and moderate specificity (80%) for
      2 or more new lesions. These models are inaccurate for targeting resources at
      high risk people. However, low risk individuals can be more accurately
      identified. If the activity of early tooth decay lesions, in low risk people, are
      monitored over time and only lesions beyond 1/3 of the dentin depth are filled,
      the number of annual fillings may be reduced by 50%. Currently, most US dental
      schools do not teach risk assessment for caries and encourage early treatment of
      lesions leading to a repair destruction cycle. The combination of a decision
      support system with a moderate accuracy specificity risk model for predicting low
      risk individuals may produce a significant improvement in caries management.

PMID- 9929286
TI  - A fuzzy classification system to predict renal artery restenosis after
      angioplasty.
AB  - Percutaneous transluminal angioplasty (PTRA) has emerged as a promising treatment
      for patients with renovascular hypertension. However, the benefit of this
      procedure is hampered by restenosis that frequently occurs within around 6 months
      after a successful angioplasty. This paper presents a fuzzy classification system
      based on a fuzzy pattern matching model that is being developed to evaluate the
      risk of short-term restenosis. First, identified classes are represented by fuzzy
      prototypes that take into account the imprecision of the criteria. Second, the
      system is applied to angiographic features of given stenoses and provides the
      membership degree of these stenosis to the two classes "short term restenosis" or
      "no restenosis". The fuzzy classifier's performances have been tested on twenty
      two patients who underwent balloon angioplasty in the context of a French
      multicenter randomized trial EMMA. With the fuzzy classifier, restenosis were
      predicted prospectively with 100% while its sensitivity is about 73%. The fuzzy
      classification system is expected to become a reliable tool to predict PTRA
      outcomes.

PMID- 9929287
TI  - Bayesian modeling for linking causally related observations in chest X-ray
      reports.
AB  - Our natural language understanding system outputs a list of diseases, findings,
      and appliances found in a chest x-ray report. The system described in this paper
      links those diseases and findings that are causally related. Using Bayesian
      networks to model the conceptual and diagnostic information found in a chest x
      ray we are able to infer more specific information about the findings that are
      linked to diseases.

PMID- 9929288
TI  - The impact of modeling the dependencies among patient findings on classification
      accuracy and calibration.
AB  - We present a new Bayesian classifier for computer-aided diagnosis. The new
      classifier builds upon the naive-Bayes classifier, and models the dependencies
      among patient findings in an attempt to improve its performance, both in terms of
      classification accuracy and in terms of calibration of the estimated
      probabilities. This work finds motivation in the argument that highly calibrated
      probabilities are necessary for the clinician to be able to rely on the model's
      recommendations. Experimental results are presented, supporting the conclusion
      that modeling the dependencies among findings improves calibration.

PMID- 9929289
TI  - MediAgent: a WWW-based scalable and self-learning medical search engine.
AB  - Searching for medical information on the Internet can be tedious and frustrating
      due to the number of irrelevant entries returned from generic search engines. We
      have developed MediAgent, a scalable search engine that aims to deliver a web
      based medical search solution which is focused, exhaustive and able to keep
      improving its databases. The software package can run off a single low-end system
      and be scaled into a client-server, distributed computing architecture for high
      end needs. This scalable architecture boosts MediAgent's handling capacity to
      tens of millions of web pages. In addition to large volume handling, MediAgent is
      designed to be manageable. All subsystems are not only highly configurable, but
      also support remote, interactive management and monitoring by the system
      administrator.

PMID- 9929290
TI  - A declarative explanation framework that uses a collection of visualization
      agents.
AB  - User acceptance of a knowledge-based system depends partly on how effective the
      system is in explaining its reasoning and justifying its conclusions. The WOZ
      framework provides effective explanations for component-based decision-support
      systems. It represents explanation using explicit models, and employs a
      collection of visualization agents. It blends the strong features of existing
      explanation strategies, component-based systems, graphical visualizations, and
      explicit models. We illustrate the features of WOZ with the help of a component
      based medical therapy system. We describe the explanation strategy, the roles of
      the visualization agents and components, and the communication structure. The
      integration of existing and new visualization applications, the domain
      independent framework, and the incorporation of varied knowledge sources for
      explanation can result in a flexible explanation facility.

PMID- 9929291
TI  - DXplain on the Internet.
AB  - DXplain, a computer-based medical education, reference and decision support
      system has been used by thousands of physicians and medical students on stand
      alone systems and over communications networks. For the past two years, we have
      made DXplain available over the Internet in order to provide DXplain's knowledge
      and analytical capabilities as a resource to other applications within
      Massachusetts General Hospital (MGH) and at outside institutions. We describe and
      provide the user experience with two different protocols through which users can
      access DXplain through the World Wide Web (WWW). The first allows the user to
      have direct interaction with all the functionality of DXplain where the MGH
      server controls the interaction and the mode of presentation. In the second mode,
      the MGH server provides the DXplain functionality as a series of services, which
      can be called independently by the user application program.

PMID- 9929292
TI  - Consumer health informatics: knowledge engineering and evaluation studies of
      medical HouseCall.
AB  - The changes in reimbursement structure in health care have given rise to a
      rapidly growing focus on the consumer and this recent increase has been fueled by
      the advent of the Web. Consumer health information (CHI) systems empower the
      consumer and aim to improve doctor-patient communication. We present HouseCall, a
      CHI system. First, this paper reviews how a consumer information system can be
      derived from an existing physician knowledge base (Iliad). Second, it presents
      evaluation studies that: 1) show how consumers are eager for non 'dumbed-down'
      content with easy access, 2) demonstrate the large spectrum of topics of interest
      and the 'natural' search strategies of health care consumers.

PMID- 9929293
TI  - Optimal use of communication channels in clinical event monitoring.
AB  - We argue that the optimal use of communication channels in clinical event
      monitors is an important design consideration for these systems. We review the
      state-of-the-art in selection of communication channels, including our current
      approach--allowing users to choose the communication channel by which the event
      monitor sends each notification. We describe a new approach that we are in the
      process of developing. In this new approach, we view event monitoring as the
      decision of whether and how to send new patient data to a clinician and apply the
      principle of maximum expected utility to this decision problem. Our initial
      experience with this approach suggests that notifying clinicians of normal
      patient data may be of high utility. We also found that methods for explanation
      in uncertain reasoning may be necessary in this approach.

PMID- 9929294
TI  - Differential diagnoses of the heart disease program have better sensitivity than
      resident physicians.
AB  - We describe a prospective clinical evaluation of a computer program to assist
      with the diagnosis of heart disease. The Heart Disease Program (HDP) is a large
      diagnostic program covering most areas of heart disease and some related areas of
      general medicine. The program's output is a set of differential diagnoses with
      explanations and it can be deployed in a clinical setting using a web interface.
      A framework for assessing the complex diagnostic summaries generated by the HDP
      was developed and the program's diagnostic accuracy in a clinical setting was
      assessed. The diagnoses used for comparison came from the physician entering the
      case, a "gold standard" assigned by review of patient charts and investigations,
      and the opinions of expert cardiologists. The data collection, methods of
      comparison, example analyses and results on 114 cases are presented here. The HDP
      had a significantly higher sensitivity for both the gold standard (60%) and the
      cardiologist's diagnoses (58%) than the physicians did (39%, 34%). These findings
      were consistent in the 2 collection cohorts and for the more serious diagnoses
      alone. The significance of these findings and the many challenges in comparing
      these different diagnoses and minimizing bias are discussed.

PMID- 9929295
TI  - Therapy planning as constraint satisfaction: a computer-based antiretroviral
      therapy advisor for the management of HIV.
AB  - We applied the Protege methodology for building knowledge-based systems to the
      domain of antiretroviral therapy. We modeled the task of prescribing drug therapy
      for HIV, abstracting the essential characteristics of the problem solving. We
      mapped our model of the antiretroviral-therapy domain to the class of constraint
      satisfaction problems, and reused the propose-and-revise problem-solving method,
      from the Protege library of methods, to build an antiretroviral therapy advisor,
      ART Critic. Careful modeling and using Protege allowed us to build a useful and
      extensible knowledge-based application rapidly.

PMID- 9929296
TI  - Diagnosing community-acquired pneumonia with a Bayesian network.
AB  - We present the development and the evaluation of a Bayesian network for the
      diagnosis of community-acquired pneumonia. The Bayesian network is intended to be
      part of a larger decision support system which assists emergency room physicians
      in the management of pneumonia patients. Minimal data entry from the nurse or the
      physician, timely availability of clinical parameters, and high accuracy were
      requirements we tried to meet. Data from more than 32,000 emergency room patients
      over a period of 2 years (June 1995-June 1997) were extracted from the clinical
      information system to train and test the Bayesian network. The network performed
      well in discriminating patients with pneumonia from patients with other diseases.
      The Bayesian network achieved a sensitivity of 95%, a specificity of 96.5%, an
      area under the receiver operating characteristic of 0.98, and a predictive value
      positive of 26.8%. Our feasibility study demonstrates that the proposed Bayesian
      network is an appropriate method to detect pneumonia patients with high accuracy.
      The study suggests that the proposed Bayesian network may represent a successful
      component within a larger decision support system for the management of community
      acquired pneumonia.

PMID- 9929297
TI  - Towards interoperability of information sources within a hospital Intranet.
AB  - Information is usually available in heterogeneous data format and various legacy
      sources. Interoperability appears to be a major approach for applications to
      access information. The project ARIANE is devoted to provide end-users with an
      easy to use and natural access to information databases. In this frame we defined
      actors able to operate the mediation between end-users and information servers: a
      "broker" which selects appropriate resources and "mediators" which access data
      suppliers. We have implemented a web-oriented stand-alone prototype accessing
      three types of information sources: a bibliographical server, a SQL database
      server and a hypertext server. Both broker and mediators exploit the Unified
      Medical Language System knowledge sources, especially the Information Sources Map
      which allows a way to identify information servers.

PMID- 9929299
TI  - MCM generator: a Java-based tool for generating medical metadata.
AB  - In a previous paper we introduced the need to implement a mechanism to facilitate
      the discovery of relevant Web medical documents. We maintained that the use of
      META tags, specifically ones that define the medical subject and resource type of
      a document, help towards this goal. We have now developed a tool to facilitate
      the generation of these tags for the authors of medical documents. Written
      entirely in Java, this tool makes use of the SAPHIRE server, and helps the author
      identify the Medical Subject Heading terms that most appropriately describe the
      subject of the document. Furthermore, it allows the author to generate metadata
      tags for the 15 elements that the Dublin Core considers as core elements in the
      description of a document. This paper describes the use of this tool in the
      cataloguing of Web and non-Web medical documents, such as images, movie, and
      sound files.

PMID- 9929298
TI  - Peer reviewing and curating the health care information infrastructure:
      experiences and recommendations.
AB  - As part of a digital health sciences library's continuous quality improvement
      process, a digital textbook of common medical problems was created which
      contained links to authoritative medical information on the Internet for patients
      and health care providers. The accomplishments of this project were the: 1)
      Identification of 50 common medical problems, 2) Development of a methodology for
      identifying authoritative medical information related to these problems, 3)
      Creation of a digital textbook containing links to this information with a
      problem-based interface, 4) Development of a methodology to allow local peer
      review of this information, and 5) Evaluation of the use of the information and
      the local peer review methodology.

PMID- 9929300
TI  - HCFA documentation guidelines and the need for discrete data: a golden
      opportunity for applied health informatics.
AB  - BACKGROUND: The medical community is shocked by the complexity of the
      documentation now required to support the Medicare billing codes. This situation
      represents an opportunity for Electronic Medical Records that use discrete data
      to become a central factor at the point of care by fulfilling these stringent
      documentation specifications. METHODS: This empirical study explores whether a
      discrete data EMR has the ability to generate automatically a report describing
      what billing code is consistent with the documentation recorded. We tested this
      hypothesis on HBOC Pathways SMR by attempting to create algorithms that reflected
      the HCFA guidelines. We validated this process using historical records from the
      Cleveland Clinic. RESULTS: All the data elements required by HCFA were available
      as discrete data. Using algorithms, the billing code consistent with the
      documentation of the health care encounter could be automatically generated.
      CONCLUSIONS: EMRs using discrete data can substantially reduce the burden placed
      on health care providers by HCFA's new documentation guidelines. This benefit
      creates a window of opportunity for health informatics to become an integral tool
      in the provision of health care. Using EMRs for billing purposes can help achieve
      the loftier goal of using EMRs for quality improvement.

PMID- 9929302
TI  - Developing search strategies for detecting high quality reviews in a hypertext
      test collection.
AB  - OBJECTIVE: To identify search strategies for retrieving high quality review
      studies about etiology, prognosis, therapy, and diagnosis from World Wide Web
      (WWW) medical documents. DESIGN: Observational study of the performance of search
      strategies based on terms found in high quality review articles in a collection
      of hypertext medical documents from the WWW. MEASUREMENTS: The sensitivity and
      specificity of search strategies for review articles in general and with a
      specific focus were determined by comparison to a manual review of a collection
      of hypertext medical documents. RESULTS: A total of 1058 hypertext medical
      documents from seven governmental and academic WWW sites were included in the
      study collection. About 16% of the documents in the collection met the criteria
      for high quality review documents. Search strategies for review documents were
      identified that had 87% sensitivity and 95% specificity. Compared to simple
      strategies combining the term "review" and the article focus, more complex
      strategies based on terms found in high quality studies were more sensitive in
      identifying review articles of a given focus. These more complex strategies had a
      sensitivity of 83% for diagnosis, 85% for therapy, 79% for prognosis, and 88% for
      etiology, while the simple strategies had a sensitivity of 88%, 74%, 38%, and
      46%, respectively. In addition, the more complex strategies were more specific
      for high quality review articles on diagnosis and therapy. CONCLUSION: Search
      strategies can be identified that enhance retrieval of review documents and
      review documents of specific focus from a collection of WWW hypertext medical
      documents.

PMID- 9929301
TI  - Information needs research in the era of the digital medical library.
AB  - The rapid adoption of Internet-accessible information resources by the clinical
      community, has resulted in an exponential growth in the variety and type of
      clinical information resources along with an increasing diversity of information
      technologies to deliver clinical information. To date, little formal work has
      been done to investigate the significance of new information technologies such as
      Internet-based digital libraries and multimedia record systems on clinical
      information need or information seeking behavior. In the work described in this
      paper, we highlight some results from our recent multimethod research design and
      investigation of the information-seeking behavior of Pittsburgh area medical
      oncologists to argue for the use of a multimethod research design as an essential
      component of any investigation of clinical information need and information
      seeking behavior in the era of the digital medical library.

PMID- 9929303
TI  - Versatility of a multilingual and bi-directional approach for medical language
      processing.
AB  - At the dawn of the 21st century, we are experiencing an exponential growth of
      online information that is mostly textual, and that benefits from new electronic
      media, such as the World Wide Web (WWW), to be broadly diffused across borders.
      However, there is a gap to bridge between holding information and accessing in a
      relevant way the deep underlying knowledge. Multilingual natural language
      processing (NLP), once tuned, is certainly the best solution to cope with this
      era of textual information. This paper focuses on the lesson learned through the
      joint development of an analyzer and a generator of medical language, within a
      multilingual context. Concrete examples, derived from the efforts under way in
      the European GALEN-IN-USE project, illustrate the use of these linguistic tools
      for the handling of surgical procedures.

PMID- 9929304
TI  - SAPHIRE International: a tool for cross-language information retrieval.
AB  - The world's foremost medical literature is written in English, yet much of the
      world does not speak English as a primary language. This has led to increasing
      research interest in cross-language information retrieval, where textual
      databases are queried in languages other than the one in which they are written.
      We describe enhancements to the SAPHIRE concept-retrieval system, which maps free
      text documents and queries to concepts in the UMLS Metathesaurus, that allow it
      to accept text input and provide Metathesaurus concept output in any of six
      languages: English, German, French, Russian, Spanish, and Portuguese. An example
      of the use of SAPHIRE International is shown in the CliniWeb catalogue of
      clinically-oriented Web pages. A formative evaluation of German terms shows that
      additional work is required in handling plural and other suffix variants as well
      as expanding the breadth of synonyms in the UMLS Metathesaurus.

PMID- 9929305
TI  - The integration of a novice user interface into a professional modeling tool.
AB  - This paper describes a software tool, the Oncology Thinking Cap (OncoTCAP) and
      reports on our efforts to develop a novice user interface to simplify the task of
      describing biological models of cancer and its treatment. Oncology Thinking Cap
      includes a modeling tool for making relationships explicit and provide dynamic
      feedback about the interaction between cancer cell kinetics, treatments, and
      patient outcomes. OncoTCAP supports student learning by making normally invisible
      processes visible and providing a representational tool that can be used to
      conduct thought experiments. We also describe our novice interface and report the
      results of initial usability testing.

PMID- 9929306
TI  - Contextual and temporal clinical guidelines.
AB  - In this paper, we propose an approach for managing clinical guidelines. We sketch
      a modular architecture, allowing us to separate conceptually distinct aspects in
      the management and use of clinical guidelines. In particular, we describe the
      clinical guidelines knowledge representation module and we sketch the acquisition
      module. The main focus of the paper is the definition of an expressive formalism
      for representing clinical guidelines, which allows one to deal with the context
      dependent character of clinical guidelines and takes into account different
      temporal aspects.

PMID- 9929307
TI  - Electronic surveillance of disease states: a preliminary study in electronic
      detection of respiratory diseases in a primary care setting.
AB  - The present project is a step by step description of the creation of a
      computerized surveillance system using historical information derived from
      automated expert system acquisition. Since historical information is in many
      cases not sufficient for establishing an individual's medical diagnosis, the
      accuracy of surveillance is measured against the "gold standard" diagnosis
      provided by a panel of physicians. It was possible to survey within acceptable
      limits of accuracy in the conditions of the project. The results reveal a high
      level of sensitivity by computer surveillance as well as an accurate ability of
      electronic tracking of disease incidence over a period of time. However, further
      investigation into the accuracy of electronic surveillance and selection of
      symptoms used to define a disease should be studied. The feasibility of employing
      electronic historical medical information to survey disease has potential in
      providing real-time epidemiological data.

PMID- 9929308
TI  - Design of a modular, extensible decision support system for arrhythmia therapy.
AB  - We developed a decision-support system for evaluation of treatment alternatives
      for supraventricular and ventricular arrhythmias. The system uses independent
      decision models that evaluate the costs and benefits of treatment for recurrent
      atrioventricular-node reentrant tachycardia (AVNRT), and of therapies to prevent
      sudden cardiac death (SCD) in patients at risk for life-threatening ventricular
      arrhythmias. Each of the decision models is accessible through a web-based
      interface that enables remote users to browse the model's underlying evidence and
      to perform analyses of effectiveness, cost effectiveness, and sensitivity to
      input variables. Because the web-based interface is independent of the models, we
      can extend the functionality of the system by adding decision models. This system
      illustrates that the use of a library of web-accessible decision models provides
      decision support economically to widely dispersed users.

PMID- 9929309
TI  - TraumaTalk: content-to-speech generation for decision support at point of care.
AB  - Communicating information in clinical environments is a crucial concern for
      medical decision support systems. Some systems can provide this support through
      text output that can be read by the clinician either from a screen or hard copy.
      However, speech is often a more appropriate way of conveying information in cases
      where the decision maker's eyes are already committed to another task or in cases
      where the telephone is the mode of communication. Some systems synthesize speech
      directly from text, while others piece together bits of pre-recorded human
      speech. In either case, producing correct intonation is vital because intonation
      both aids the listener's comprehension and conveys discourse meaning not
      necessarily evident in the words alone. Although systems that use text-to-speech
      or human recorded speech segments sometimes attempt to provide good intonation,
      they are severely hampered by the fact that intonation spans entire clauses.
      Systems that connect phonemes, words, or phrases fail to capture this. This paper
      describes a content-to-speech system that provides spoken decision support for
      trauma care that is correctly intoned over full clauses.

PMID- 9929310
TI  - A COSTAR interface using WWW technology.
AB  - The concentration of industry on modern relational databases has left many
      nonrelational and proprietary databases without support for integration with new
      technologies. Emerging interface tools and data-access methodologies can be
      applied with difficulty to medical record systems which have proprietary data
      representation. Users of such medical record systems usually must access the
      clinical content of such record systems with keyboard-intensive and time
      consuming interfaces. COSTAR is a legacy ambulatory medical record system
      developed over 25 years ago that is still popular and extensively used at the
      Massachusetts General Hospital. We define a model for using middle layer services
      to extract and cache data from non-relational databases, and present an intuitive
      World-Wide Web interface to COSTAR. This model has been implemented and
      successfully piloted in the Internal Medicine Associates at Massachusetts General
      Hospital.

PMID- 9929311
TI  - A graphical user interaction model for integrating complex clinical applications:
      a pilot study.
AB  - We have developed and implemented a multi-faceted, graphical user interaction
      model for an advanced clinical information system. This paper describes a
      classification scheme for applications used by clinicians in their daily work,
      discusses the way clinicians interact with these applications, and the issues
      that arise during these user interactions. Through its emphasis on support for
      application interoperation, the graphical user interface that implements the
      model presents a single, consistent, context to the user, and thereby helps
      maintain patient safety and ensure ease of use.

PMID- 9929312
TI  - Hospitexte: towards a document-based hypertextual electronic medical record.
AB  - The patient record is a repository for knowledge about a patient. Work in
      Artificial Intelligence and knowledge representation has evidenced the intrinsic
      difficulty of formalizing knowledge for computer processing. It is therefore not
      a surprise that most attempts at computerizing the patient record have only had a
      limited degree of success or applicability. We claim that this is due to the fact
      that medicine is an empirical domain, and thus fundamentally resists
      formalization. Therefore, the only way medical knowledge can be fully expressed
      is through natural languages which is indeed what clinicians actually use. We
      proposed and designed an electronic medical record which adheres to this
      hypothesis and where structured documents play a prominent role.

PMID- 9929313
TI  - SGML and XML as interchange formats for HL7 messages.
AB  - OBJECTIVE: To report on the use of SGML and XML (a proper subset of SGML) as
      transfer syntaxes for HL7 Version 2.3 and Version 3.0 messages. METHODS: The
      methodology has focused largely on two questions: Can it be done? How best to do
      it? The first question is addressed by attempting to build an SGML/XML
      representation of HL7 messages. The second question requires a consideration of
      several metrics: message length, speed of message creation and parsing,
      interversion compatibility, local customization, conformance determination, and
      the availability of software tools and skill on the format. RESULTS: Detailed
      specifications for expressing HL7 in SGML and XML have been developed. Some HL7
      requirements are not readily expressed, while some ambiguous areas of the HL7
      standard are made explicit in the SGML/XML representation. With the current
      design, an SGML/XML parser can extract any component of any data type from a
      message. CONCLUSIONS: SGML and XML can both serve as implementable message
      specifications for HL7 Version 2.3 and Version 3.0 messages. The ability to
      explicitly represent an HL7 requirement in SGML/XML confers the ability to
      validate that requirement with an SGML parser. The optimal message representation
      will be a balance of functional, technical, and practical requirements.

PMID- 9929314
TI  - Extensible markup language (XML) in health care: integration of structured
      reporting and decision support.
AB  - The Extensible Markup Language (XML) is a newly adopted Internet protocol for
      data interchange designed to bring the key features of the Standard Generalized
      Markup Language (SGML; ISO 8879:1986)--extensibility, complex structures, and
      validation--to the World Wide Web. In this paper, we describe an architecture
      that uses XML to mediate between disparate client-server systems for structured
      reporting and decision support.

PMID- 9929315
TI  - An XML portable chart format.
AB  - The clinical chart remains the fundamental record of outpatient clinical care. As
      this information migrates to electronic form, there is an opportunity to create
      standard formats for transmitting these charts. This paper describes work toward
      a Portable Chart Format (PCF) that can represent the relevant aspects of an
      outpatient chart. The main goal of the format is to provide a packaging medium
      for outpatient clinical charts in a transfer of care scenario. A secondary goal
      is to support the aggregation of comparable clinical data for outcomes analysis.
      The syntax used for PCF is Extended Markup Language (XML), a W3C standard. The
      structure of the PCF is based on a clinically relevant view of the data. The data
      definitions and nomenclature used are based primarily on existing clinical
      standards.

PMID- 9929316
TI  - Using the extensible markup language (XML) in automated clinical practice
      guidelines.
AB  - Much work has been done in the area of web-based clinical practice guidelines.
      Issues such as representation, description, architectures, and implementation
      have been explored previously. Most if not all of these web-based applications
      rely exclusively on HTML, the HyperText Markup Language. In the process of
      prototyping a guideline service to be used in a diabetes operations improvement
      project, we developed a model for a guideline engine that makes use of the
      Extensible Markup Language (XML), both as an interface to the engine and as a
      vehicle for delivering structured guideline content. We feel that XML may offer
      advantages in implementing guideline services that are difficult (if not
      impossible) to accomplish with HTML alone.

PMID- 9929317
TI  - Compositional concept representation using SNOMED: towards further convergence of
      clinical terminologies.
AB  - This paper describes several approaches to the expression and coding of clinical
      concepts as composites of elementary entities, and describes an approach based on
      SNOMED RT that may permit further convergence of clinical terminology efforts. We
      explain the shortcomings of previous approaches to compositional concept
      representation, as well as the reasons for SNOMED's current approach, which
      adopts a foundation based in description logics (DLs). The DL model has many
      advantages: it establishes a formal semantics for SNOMED assertions and suggests
      a syntax; it provides a basis for understanding expressiveness and computational
      complexity, through correspondence with known results from DLs; and it helps to
      clarify the relationships among existing concept representation methods in
      SNOMED, NHS Clinical Terms (formerly the Read Codes), and GALEN, making a path to
      convergence more clear.

PMID- 9929318
TI  - Setting standards for nursing data sets in information systems.
AB  - The American Nurses Association (ANA) has established the Nursing Information and
      Data Set Evaluation Center (NIDSEC). The purpose of this Center is to develop and
      disseminate standards pertaining to information systems that support the
      documentation of nursing practice, and to evaluate voluntarily submitted
      information systems against these standards. The need for an evaluation center
      arises out of a long history of calls for standards pertaining to nursing data
      and to information systems. Standards have been developed to evaluate the
      completeness, accuracy and appropriateness of four dimensions of nursing data
      sets and the systems that contain them 1) nomenclature, 2) clinical content, 3)
      clinical data repository, and 4) general system characteristics. Once the
      standards and scoring mechanisms were established, they were tested for
      reliability and validity. A Content Validity Index (CVI) of 0.875 was established
      for the scoring tool.

PMID- 9929319
TI  - Updating a bibliography using the related articles function within PubMed.
AB  - Comprehensive bibliographies are useful for conducting reviews of the literature,
      and for assessing the progress within a field. These bibliographies may be broad
      and inclusive, or focused and precise in their inclusion criteria. In either
      case, the task of maintaining a complete bibliography within a particular area of
      research is made difficult by the diversity, complexity and huge volume of newly
      published literature. In an effort to effectively and automatically retrieve
      relevant literature, different search strategies and indexing tools have been
      developed, including the RELATED ARTICLES function provided with the PubMed
      system. In this paper, we report a program for incremental updates of a
      bibliography using the PubMed RELATED ARTICLES function. Given a highly
      specialized starting bibliography of experimental measurements of the structure
      of the 30S bacterial ribosomal subunit, the system was applied to find additional
      relevant references. For this particular task, the system has a recall of 75%, a
      strict precision of 32% and a partial precision of 42%. Our results are notable
      because although the RELATED ARTICLES function is purely statistical, it is
      nonetheless able to select a very narrowly defined set of articles from the
      literature. We discuss the tradeoffs between having a user to evaluate many
      articles of possible interest in a single session, versus asking a user to
      evaluate a small set of articles on a periodic basis.

PMID- 9929320
TI  - A tagging system for section headings in a CEN standard on patient record.
AB  - CEN is developing a series of standards for transmission of patient records. We
      present here preliminary results to produce a standard on section headings in
      record systems. Each record system uses its own scheme of headings, depending on
      specialty, National regulations and tasks; users cannot accept a unique, standard
      scheme. Enumerating all possible headings in all National languages is not
      necessary for a safe and faithful transmission of records. The focus of CEN
      standard is shifting from the headings to a system of tags that can be tied to
      them. We want to convey just the crucial properties to assure correct data
      handling by receivers. Our tagging system is organized into 5 clusters: C0
      Nature, i.e. tags to identify the nature of data; C1 Safety context, i.e.
      essential tags that convey the main context of data; C2 Interpretation, i.e. tags
      about interpretation of data in the original context by the original user; C3
      Intention, i.e. additional tags to make explicit the links that reveal sender's
      intentions and goals; C4 Organization, i.e. further tags to show the organization
      of the original record. Although tags were conceived for messages, they should be
      present in local systems since data generation. In fact, tags can be used to
      organize data within a record and allow for multiple views, without imposing a
      unique, fixed structure to the record.

PMID- 9929321
TI  - Morpho-semantic parsing of medical expressions.
AB  - The task of editing, indexing, storing, and retrieving medical expressions within
      medical records remains the main objective for the years to come. Therefore, the
      need for a parser with semantic capabilities able to robustly extract an
      essential part of the knowledge embedded in the medical record is paramount. The
      minimal requirements before considering clinical trials are that such a system
      has to be in position to handle any source of medical information and to
      conveniently grasp the main key concepts with low silence, good recognition of
      modalities and acceptable noise. This paper shows that the potential of morpho
      semantic parsing is high to meet these conditions. This technique is an important
      complement to the traditional lexical approach and to expression-oriented systems
      like controlled vocabularies.

PMID- 9929322
TI  - A randomized controlled trial of automated term composition.
AB  - OBJECTIVE: To compare the ability of an Automated Term Composition (ATC)
      algorithm with non-compositional mappings to provide coverage (exact mappings to
      a controlled vocabulary) for a randomly selected set of free text entries which
      were entered as headings to the Impression section of the clinical notes system
      at the Mayo Foundation. We also compare the results of four evaluators to
      determine the inter-observer variability and the variance between term sets, with
      respect to the accuracy of the mappings and the reliability of the failure
      analysis. METHODS: From a corpus of approximately 1,000,000 unique terms entered
      into the Impression/Report/Plan section of the clinical notes system in the
      calendar year 1997, we randomly selected 1,000 terms. We then further randomized
      these 1,000 terms into two groups of 500 (Sets A and B). We constructed two
      copies of the same term matching interface, one without ATC (alpha) and one with
      ATC (beta). We took four expert Indexers and assigned them to one of the
      following tasks. The first reviewer (R1) compared set A using the alpha program
      and then set B using the beta program (R1(Aalpha + Bbeta)). The second compared
      set A using the alpha program and then set B using the alpha program (R2(A + B)
      alpha). The third compared set B using the beta program and then set A using the
      beta program (R3(B + A) beta). The fourth compared set A using the beta program
      and then set B using the alpha program (R4(Abeta + Balpha)). RESULTS: The program
      with Automated Term Composition mapped 540 out of the 1,000 Concepts correctly
      (54.0%). The same program without ATC mapped only 276 out of the 1,000 Concepts
      correctly (27.6%). Therefore the program with ATC was significantly more
      effective at matching concepts in our problem lists than the same search engine
      without ATC (p < 0.0001; McNemar Method). These figures result from the
      comparison of the alpha program with the beta program by reviewers one and four.
      Failure analysis showed that with the alpha version 425 out of the 724 mismatches
      were because a base concept was missing from the retrieval set (58.7%) and 299
      mismatches were from missing qualifiers or modifiers or both (41.3%). In the beta
      version of the program (with ATC) 340 out of the 460 mismatches were secondary to
      there being a missing base concept in the retrieval set (73.9%) and only 120
      mismatches due to missing modifiers and or qualifiers (26.1%). CONCLUSIONS:
      Automated term composition provided significantly better coverage of a randomly
      chosen set of patient problems, diagnosed at the Mayo Clinic during the 1997
      calendar year, when compared with the same information retrieval system without
      ATC. We believe that these results speak further to the excellent content
      coverage provided by the UMLS metathesaurus. These authors believe that increased
      structure, normalization of UMLS content and semantics, and better tools to make
      use of the currently available content such as automated term composition, are
      what is needed to leverage the production of commercially viable tools that
      provide access to controlled vocabularies for medicine.

PMID- 9929324
TI  - Evaluating lexical variant generation to improve information retrieval.
AB  - Techniques for managing lexical variation constitute an integral part of
      information retrieval systems. We report on a series of experiments aimed at
      evaluating LVG, a lexical variant management tool which addresses the particular
      problems involved in matching health related vocabularies to concepts in the
      Unified Medical Language System (UMLS) Metathesaurus. Experiments conducted on
      data from the Large Scale Vocabulary Test indicate the effectiveness of this
      approach to managing biomedical information.

PMID- 9929323
TI  - Converting an integrated hospital formulary into an object-oriented database
      representation.
AB  - Controlled Medical Vocabularies (CMVs) have proven to be extremely useful in
      their support of the tasks of information sharing and integration, communication
      among various software applications, and decision support. Modeling a CMV as an
      Object-Oriented Database (OODB) provides additional benefits such as increased
      support for vocabulary comprehension and flexible access. In this paper, we
      describe the process of modeling and converting an existing integrated hospital
      formulary (i.e., set of pharmacological concepts) into an equivalent OODB
      representation, which, in general, we refer to as an Object-Oriented Healthcare
      Vocabulary Repository (OOHVR). The source for our example OOHVR is a formulary
      provided by the Connecticut Healthcare Research and Education Foundation (CHREF).
      Utilizing this source formulary together with the semantic hierarchy composed of
      major and minor drug classes defined as part of the National Drug Code (NDC)
      directory, we constructed a CMV that was eventually converted into its OOHVR form
      (the CHREF-OOHVR). The actual conversion step was carried out automatically by a
      program, called the OOHVR Generator, that we have developed. At present, the
      CHREF-OOHVR is running on top of ONTOS, a commercial OODB management system, and
      is accessible on the Web.

PMID- 9929325
TI  - Discovering the modifiers in a terminology data set.
AB  - We recently conducted a study of a subset of the data collected in the NLM/AHCPR
      Large Scale Vocabulary Test (LSVT). We studied those 11,387 terms in the LSVT
      data that were narrower in meaning than the UMLS concepts mapped to. We
      hypothesized that when one term is narrower in meaning than another, the first
      and second terms are likely to differ primarily by modification. We compared
      three lexical processing methods of increasing sophistication and measured the
      ability of each of these methods to correctly identify the modifiers in the data
      set. The results indicate that when using the most powerful of the methods, 63%
      of the term pairs were found to differ only by premodification, by
      postmodification or by both, 31% share some lexical material, and the remaining
      6% have no lexical items in common. The implications of the study are discussed.

PMID- 9929326
TI  - A "lexically-suggested logical closure" metric for medical terminology maturity.
AB  - Medical Terminologies are becoming increasingly expressive secondary to their
      increase in size, and are becoming increasingly difficult to analyze secondary to
      inconsistencies in their use and complex interrelationships that are often not
      explicitly defined. To address these problems, SNOMED-RT is being developed to
      allow consistent use, and to define explicitly interrelationships between terms.
      Ensuring the quality of a terminology system like SNOMED-RT presents new
      challenges which we are trying to address with theoretically-grounded
      methodologies for quality management. Here we describe an initial metric toward
      achieving this goal called "lexically-suggested logical closure." We explain how
      this metric can be useful for tracking the maturity and quality of a terminology,
      and apply this metric to track the progress of SNOMED-RT development over a
      portion of its life-cycle.

PMID- 9929327
TI  - Reproducibility of interpreting "and" and "or" in terminology systems.
AB  - High quality terminologies are a fundamental requirement in a range of health
      care applications. To ensure high quality terminologies we should reflect about
      the understandability, reproducibility and utility criteria within a terminology.
      This paper describes efforts to improve the understandability of SNOMED. We
      describe the problem related to the grammatical conjunctions "and" and "or" and
      how we applied basic semantic rules defined by the SNOMED Editorial Board. The
      results show that the meaning of "and" and "or" in SNOMED can be made explicit in
      almost all cases and can be done in a reasonable, reliable, and reproducible
      manner.

PMID- 9929328
TI  - A clinical terminology in the post modern era: pragmatic problem list
      development.
AB  - A brief review of the rich heritage of classifications and terminologies is the
      background for a description of the Mayo Clinic's clinical terminology
      development. Vender specific system constraints prompted the scope and style of
      an interim problem list vocabulary. We describe the sources and review process
      which led to a working terminology for use in a Computer-based Patient Record
      (CPR). Because terminology development is often subjective and metrics against
      which to measure the quality of individual human judgements are few, we decided
      to compare the selection of preferred terms made by general internists with those
      made by sub-specialists. A significant difference between a sub-specialist's
      assignment of preferred terms and a general internist's (948 vs. 2271, P < 0.001)
      was observed. Sub-specialists were less than half as likely as a generalist to
      designate a term as a preferred form. These results emphasize the need for sub
      specialty editing when assigning preferred terms to concepts.

PMID- 9929329
TI  - A proposal for incorporating health level seven (HL7) vocabulary in the UMLS
      Metathesaurus.
AB  - The HL7 Vocabulary Technical Committee (TC) was organized to select and maintain
      the vocabulary used in HL7 messages. The goal is to make implementations of the
      Version 3 HL7 Standard more plug-and-play compatible. In order to make the
      vocabulary readily accessible to the public, HL7 is collaborating with the U.S.
      National Library of Medicine (NLM) to include HL7 vocabulary in the Unified
      Medical Language System (UMLS) Metathesaurus. This article describes a proposal
      for how HL7 data elements and coded values can be represented accurately in the
      relational tables of the UMLS Metathesaurus.

PMID- 9929331
TI  - An ontological analysis of the UMLS Metathesaurus.
AB  - Paper-based terminology systems cannot satisfy anymore the new desiderata of
      healthcare information systems: the demand for re-use and sharing of patient
      data, their transmission and the need of semantic-based criteria for purposive
      statistical aggregation. The unambiguous communication of complex and detailed
      medical concepts is now a crucial feature of medical information systems.
      Ontologies can support a more effective data and knowledge sharing in medicine.
      In this paper we briefly survey our ontological analysis and integration of
      various top-levels of terminologies and we report the main results of the
      ontological analysis of the UMLS Metathesaurus.

PMID- 9929330
TI  - Validation of clinical problems using a UMLS-based semantic parser.
AB  - The capture and symbolization of data from the clinical problem list facilitates
      the creation of high-fidelity patient resumes for use in aggregate analysis and
      decision support. We report on the development of a UMLS-based semantic parser
      and present a preliminary evaluation of the parser in the recognition and
      validation of disease-related clinical problems. We randomly sampled 20% of the
      26,858 unique non-dictionary clinical problems entered into OMR (Online Medical
      Record) between 1989 and August, 1997, and eliminated a series of qualified
      problem labels, e.g., history-of, to obtain a dataset of 4122 problem labels.
      Within this dataset, the authors identified 2810 labels (68.2%) as referring to a
      broad range of disease-related processes. The parser correctly recognized and
      validated 1398 of the 2810 disease-related labels (49.8 +/- 1.9%) and correctly
      excluded 1220 of 1312 non-disease-related labels (93.0 +/- 1.4%). 812 of the 1181
      match failures (68.8%) were caused by terms either absent from UMLS or modifiers
      not accepted by the parser; 369 match failures (31.2%) were caused by labels
      having patterns not recognized by the parser. By enriching the UMLS lexicon with
      terms commonly found in provider-entered labels, it appears that performance of
      the parser can be significantly enhanced over a few subsequent iterations. This
      initial evaluation provides a foundation from which to make principled additions
      to the UMLS lexicon locally for use in symbolizing clinical data; further
      research is necessary to determine applicability to other health care settings.

PMID- 9929332
TI  - Beyond synonymy: exploiting the UMLS semantics in mapping vocabularies.
AB  - The Unified Medical Language System (UMLS) contains semantic information about
      terms from various sources, each concept can be understood and located by its
      relationships to other concepts: this is a result of the organizing principle of
      semantic locality. We describe a method in which the semantic relationships
      between concepts are used to map concepts from different vocabularies in the
      UMLS. Applied to mapping concepts to MeSH, this method is able to map 50 to 65%
      of the non-MeSH concepts to MeSH. A manual review of the mapping shows a
      relevance rate of 61%. Causes of failure include a lack of consistently
      represented relationships in the UMLS, and some inconsistencies in the
      categorization of the concepts. The limits of this method are discussed, as well
      as possible adaptations for other uses.

PMID- 9929333
TI  - The digital anatomist foundational model: principles for defining and structuring
      its concept domain.
AB  - We define a foundational model as an abstraction of a body of knowledge that
      explicitly declares the principles and concepts necessary for coherently and
      consistently modelling a knowledge domain. Principles for a foundational model of
      anatomy are defined and used to specify the components of such a model. These
      components include an anatomy ontology (Ao), an anatomical structural abstraction
      (ASA), an anatomical transformation abstraction (ATA) and metaknowledge (Mk),
      which comprises the rules for representing relationships in the other three
      components of the model. The foundational model Fm is therefore specified as the
      four-tuple Fm = (Ao,ASA,ATA,Mk). We hypothesize that this abstraction captures
      the information that is sufficient and necessary for describing the anatomy of
      any physical entity that constitutes the body, as well as that of the body
      itself.

PMID- 9929334
TI  - The potential of the digital anatomist foundational model for assuring
      consistency in UMLS sources.
AB  - Inconsistent anatomical concept representation can be identified in anatomy
      textbooks and hard copy term lists, as well as in UMLS source vocabularies and
      other controlled medical terminologies. In this report we select some examples of
      inconsistent representations of anatomical concepts, and illustrate how these
      inconsistencies can be explained and reconciled by the Digital Anatomist
      Foundational Model. We use this process for gaining a measure of the validity of
      the logic-based Model.

PMID- 9929335
TI  - Part-whole reasoning in medical ontologies revisited--introducing SEP triplets
      into classification-based description logics.
AB  - The development of powerful and comprehensive medical ontologies that support
      formal reasoning on a large scale is one of the key requirements for clinical
      computing in the next millennium. Taxonomic medical knowledge, a major portion of
      these ontologies, is mainly characterized by generalization and part-whole
      relations between concepts. While reasoning in generalization hierarchies is
      quite well understood, no fully conclusive mechanism as yet exists for part-whole
      reasoning. The approach we take emulates part-whole reasoning via classification
      based reasoning using SEP triplets, a special data structure for encoding part
      whole relations that is fully embedded in the formal framework of standard
      description logics.

PMID- 9929337
TI  - Clinical administration procedures in the Read Thesaurus: extending the ENV 1828
      model to support regional terminology requirements.
AB  - Documentation of the administrative aspects of clinical practice (fee claims,
      referrals, visits etc.) is essential and a controlled terminology for the
      electronic health care record needs to support this requirement. The Read Codes-
      used in the United Kingdom for over 10 years--include a chapter of administration
      terms for this purpose. The latest version, the Read Thesaurus, adopts a
      partially compositional approach to concept representation. We describe an
      extension of the ENV 1828 surgical procedure scheme developed as a provisional
      model to represent administrative procedures. Applicable concept fields, semantic
      links and modifiers are identified and compared. A compositional approach appears
      to provide a flexible and manageable method of representing administrative
      procedures, and readily accommodates regional variations.

PMID- 9929336
TI  - Knowledge discovery and data mining to assist natural language understanding.
AB  - As natural language processing systems become more frequent in clinical use,
      methods for interpreting the output of these programs become increasingly
      important. These methods require the effort of a domain expert, who must build
      specific queries and rules for interpreting the processor output. Knowledge
      discovery and data mining tools can be used instead of a domain expert to
      automatically generate these queries and rules. C5.0, a decision tree generator,
      was used to create a rule base for a natural language understanding system. A
      general-purpose natural language processor using this rule base was tested on a
      set of 200 chest radiograph reports. When a small set of reports, classified by
      physicians, was used as the training set, the generated rule base performed as
      well as lay persons, but worse than physicians. When a larger set of reports,
      using ICD9 coding to classify the set, was used for training the system, the rule
      base performed worse than the physicians and lay persons. It appears that a
      larger, more accurate training set is needed to increase performance of the
      method.

PMID- 9929338
TI  - Validating clinical terminology structures: integration and cross-validation of
      Read Thesaurus and GALEN.
AB  - A European pre-standard and an intermediate representation facilitated exchange
      of two independently authored compositional knowledge bases: one formal and
      automatically classified, the other manually classified. The exchange highlights
      different strengths and weaknesses in each approach, and offers a mechanism for
      partial, mutual quality assurance.

PMID- 9929339
TI  - Synchronization of diverging versions of a controlled medical terminology.
AB  - To share clinical data and to build interoperable computer systems that permit
      data entry, data retrieval, and data analysis, users and systems at multiple
      sites need a shared clinical terminology. However, local sites that adopt a
      shared terminology have local needs that prompt local-terminology maintainers to
      make changes to the local version. Meanwhile, maintainers of the shared
      terminology make changes to the shared version, and the two terminologies
      diverge. I propose a formal model for managing change, with additional features
      included for the local site. If terminology maintainers follow such a model, the
      local-terminology maintainer can synchronize the local version with the shared
      version at periodic intervals. I am implementing a prototype, which I will use to
      assess the model and to study the synchronization process.

PMID- 9929340
TI  - An evaluation of natural language processing methodologies.
AB  - Medical language processing (MLP) systems that codify information in textual
      patient reports have been developed to help solve the data entry problem. Some
      systems have been evaluated in order to assess performance, but there has been
      little evaluation of the underlying technology. Various methodologies are used by
      the different MLP systems but a comparison of the methods has not been performed
      although evaluations of MLP methodologies would be extremely beneficial to the
      field. This paper describes a study that evaluates different techniques. To
      accomplish this task an existing MLP system MedLEE was modified and results from
      a previous study were used. Based on confidence intervals and differences in
      sensitivity and specificity between each technique and all the others combined,
      the results showed that the two methods based on obtaining the largest well
      formed segment within a sentence had significantly higher sensitivity than the
      others by 5% and 6%. The method based on recognizing a complete sentence had a
      significantly worse sensitivity than the others by 7% and a better specificity by
      .2%. None of the methods had significantly worse specificity.

PMID- 9929341
TI  - Automatic extraction of PIOPED interpretations from ventilation/perfusion lung
      scan reports.
AB  - Free-text documents are the main type of data produced by a radiology department
      in a hospital information system. While this type of data is readily accessible
      for clinical data review it can not be accessed by other applications to perform
      medical decision support, quality assurance, and outcome studies. In an attempt
      to solve this problem, natural language processing systems have been developed
      and tested against chest x-rays reports to extract relevant clinical information
      and make it accessible to other computer applications. We have used a natural
      language processing tool called SymText to extract relevant clinical information
      from a different type of radiology report, the Ventilation/Perfusion lung scan
      report. Results of this effort can be analyzed in terms of precision and recall.
      The overall precision was 0.88 and recall was 0.92. In addition, the natural
      language processing system functions differently in reports with and without an
      impression section. If this type of information can be successfully extracted
      from radiology reports, one can develop quality monitors for the diagnostic
      performance of the radiologist by correlating the impressions with gold standard
      data present in a hospital information system. Avoiding the manual effort
      previously necessary to create quality assurance data, can lead to a higher
      frequency of quality review in a radiology department.

PMID- 9929342
TI  - The need for a concept-based medication vocabulary as an enabling infrastructure
      in health informatics.
AB  - Users of drug information typically focus their attention at different levels of
      description in different situations, such as medication ordering or dispensing.
      Computer systems utilizing drug information to support such activities must
      accommodate these multiple perspectives. This paper presents an approach to
      conceptualizing drug descriptions at multiple levels and outlines key features of
      an underlying information model that can serve as the basis for a concept
      oriented medication vocabulary. These features include dose forms, routes of
      administration, as well as links to multiple drug classification schemes and
      medical problems. Implementation, standards, and maintenance issues related to
      the model are also discussed.

PMID- 9929343
TI  - Computer-facilitated collaboration: experiences building SNOMED-RT.
AB  - Collaborative development involving both individuals and groups is often less
      efficient than independent development because of communication overhead and
      integration costs. Despite the decreased development efficiency, collaborations
      promise more general-purpose products because of the opportunity for integration,
      with negotiation and reconciliation of diverse perspectives. Collaborations are
      also perhaps less costly when considered in contexts where there is significant
      duplication of effort. Computer-facilitated collaboration can reduce the
      communication and integration burden such that the increased effort required to
      manage a successful collaboration focuses primarily on the development of shared
      conceptual model among the developers by requiring that the work product be
      independently reproducible. This reproducibility requirement incorporates formal
      quality assurance processes into the development process. In this paper, we
      describe our initial experiences developing SNOMED-RT using such a computer
      facilitated collaborative process. We quantify the extra costs incurred to
      achieve consistency in our efforts and reproducibility of our results.

PMID- 9929344
TI  - Data dictionaries at Giessen University Hospital: past--present--future.
AB  - The concept of maintaining a medical data dictionary as a HIS core component was
      fundamental for all HIS development phases since the mid eighties at Giessen
      University Hospital. Being influenced by an early experimental installation of
      the HELP hospital information system and its PTXT data dictionary, we kept this
      approach through a number of development cycles of our own hospital information
      system. While our first data dictionary implementation (GMDD) was still very
      close to the PTXT structure (polyhierarchical design with an eight level
      hierarchy), the second generation dictionary (MDD-GIPHARM) has already been
      designed using a more flexible semantic network model. GMDD was a mainframe
      development (realized on Tandem Computers) based on the Tandem Nonstop SQL RDBMS.
      The major clinical applications established on top of the GMDD were laboratory
      results review, diagnosis documentation and physician discharge summaries. The
      MDD-GIPHARM development was initiated on PC-basis as the core of a rheumatology
      departmental system using MS-Access and then further enhanced within a research
      project to build knowledge-based functions for drug therapy. A first set of such
      functions based on MDD-GIPHARM is in routine use since 1996. Our current focus is
      to enhance MDD-GIPHARM towards an application independent vocabulary server
      (GDDS), which may be used for a variety of applications with the intranet of
      Giessen University Hospital. In this paper the evolutionary development of those
      data dictionary concepts at Giessen University Hospital is illustrated and
      compared with international activities in the last decade.

PMID- 9929345
TI  - Towards knowledge-based retrieval of medical images. The role of semantic
      indexing, image content representation and knowledge-based retrieval.
AB  - Medicine is increasingly image-intensive. The central importance of imaging
      technologies such as computerized tomography and magnetic resonance imaging in
      clinical decision making, combined with the trend to store many "traditional"
      clinical images such as conventional radiographs, microscopic pathology and
      dermatology images in digital format present both challenges and an opportunities
      for the designers of clinical information systems. The emergence of Multimedia
      Electronic Medical Record Systems (MEMRS), architectures that integrate medical
      images with text-based clinical data, will further hasten this trend. The
      development of these systems, storing a large and diverse set of medical images,
      suggests that in the future MEMRS will become important digital libraries
      supporting patient care, research and education. The representation and retrieval
      of clinical images within these systems is problematic as conventional database
      architectures and information retrieval models have, until recently, focused
      largely on text-based data. Medical imaging data differs in many ways from text
      based medical data but perhaps the most important difference is that the
      information contained within imaging data is fundamentally knowledge-based. New
      representational and retrieval models for clinical images will be required to
      address this issue. Within the Image Engine multimedia medical record system
      project at the University of Pittsburgh we are evolving an approach to
      representation and retrieval of medical images which combines semantic indexing
      using the UMLS Metathesuarus, image content-based representation and knowledge
      based image analysis.

PMID- 9929346
TI  - Unified modeling language and design of a case-based retrieval system in medical
      imaging.
AB  - One goal of artificial intelligence research into case-based reasoning (CBR)
      systems is to develop approaches for designing useful and practical interactive
      case-based environments. Explaining each step of the design of the case-base and
      of the retrieval process is critical for the application of case-based systems to
      the real world. We describe herein our approach to the design of IDEM--Images and
      Diagnosis from Examples in Medicine--a medical image case-based retrieval system
      for pathologists. Our approach is based on the expressiveness of an object
      oriented modeling language standard: the Unified Modeling Language (UML). We
      created a set of diagrams in UML notation illustrating the steps of the CBR
      methodology we used. The key aspect of this approach was selecting the relevant
      objects of the system according to user requirements and making visualization of
      cases and of the components of the case retrieval process. Further evaluation of
      the expressiveness of the design document is required but UML seems to be a
      promising formalism, improving the communication between the developers and
      users.

PMID- 9929347
TI  - Requirements for an on-line knowledge-based anatomy information system.
AB  - User feedback from the Digital Anatomist Web-based anatomy atlases, together with
      over 20 years of anatomy teaching experience, were used to formulate the
      requirements and system design for a next-generation anatomy information system.
      The main characteristic of this system over current image-based approaches is
      that it is knowledge-based. A foundational model of anatomy is accessed by an
      intelligent agent that uses its knowledge about the available anatomy resources
      and the user types to generate customized interfaces. Current usage statistics
      suggest that even partial implementation of this design will be of great
      practical value for both clinical and educational needs.

PMID- 9929348
TI  - Automatic semantic interpretation of anatomic spatial relationships in clinical
      text.
AB  - A set of semantic interpretation rules to link the syntax and semantics of
      locative relationships among anatomic entities was developed and implemented in a
      natural language processing system. Two experiments assessed the ability of the
      system to identify and characterize physico-spatial relationships in coronary
      angiography reports. Branching relationships were by far the most common observed
      (75%), followed by PATH (20%) and PART/WHOLE relationships. Recall and precision
      scores were 0.78 and 0.67 overall, suggesting the viability of this approach in
      semantic processing of clinical text.

PMID- 9929349
TI  - Integration of DICOM images into an electronic medical record using thin viewing
      clients.
AB  - Over the past five years the University of Washington has created a clinical data
      repository. This repository combines in a distributed relational database
      information from multiple departmental databases (MIND). MINDscape provides a
      platform independent, web browser view of the MIND dataset that can easily be
      linked to other information resources on the network.

PMID- 9929350
TI  - System for efficient and secure distribution of medical images on the Internet.
AB  - Because of the high compressibility of the medical images, data compression is
      desirable for digital storage despite the availability of inexpensive hardware
      for mass storage. A progressive transmission algorithm with automatic security
      filtering features for on-line medical image distribution using Daubechies'
      wavelets has been developed and is discussed in this paper. The system is
      practical for real-world applications, processing and coding each 12-bit image of
      size 512 x 512 within 2 seconds on a Pentium Pro. Besides its exceptional speed,
      the security filter has demonstrated a remarkable accuracy in detecting sensitive
      textual information within current or digitized previous medical images. The
      algorithm is of linear run time.

PMID- 9929352
TI  - Diagnostic quality of low resolution images for tele-woundcare.
AB  - The use of digital wound images would allow remote consultation between patients,
      physicians, or other caregivers over the Internet. To evaluate the efficacy and
      validity of digital images for assessment of wounds, we compared the ability and
      reliability of surgeons to diagnose and make treatment suggestions using either
      digital or slide images of several types of wounds. Twenty-four wound images on
      35-mm slides were selected for use in this study. Each slide image was digitized
      at 24-bit color with a resolution of 640 pixels horizontal by 425 pixels
      vertical, and stored as a JPEG file. Six physicians, of varying experience,
      examined the images, first in digital format and then later in the original slide
      form. Each observer assessed each wound for condition and possible treatment
      options by filling out a questionnaire using a series of yes/no questions. For
      all observers, there was an 87% agreement of answers between digital and slide
      images (p = 0.004). The agreement between the digital and slide images was also
      measured for each individual observer using a kappa coefficient. The agreement
      kappa correlated with the experience of the observer, with the kappa values
      ranging from greater than 0.8 (almost perfect agreement) for an experienced
      woundcare professional to just greater than 0.5 (moderate agreement) for a
      surgical intern. With this study, we have demonstrated the feasibility of
      distance wound consultation using digital images of a quality consistent with
      consumer-grade digital photography.

PMID- 9929351
TI  - Digital dynamic telepathology--the Virtual Microscope.
AB  - The Virtual Microscope is being designed as an integrated computer hardware and
      software system that generates a highly realistic digital simulation of analog,
      mechanical light microscopy. We present our work over the past year in meeting
      the challenges in building such a system. The enhancements we made are discussed,
      as well as the planned future improvements. Performance results are provided
      showing the system scales well, so that many users can be adequately serviced by
      an appropriately configured data server.

PMID- 9929353
TI  - Incorporating constraint-based shape models into an interactive system for
      functional brain mapping.
AB  - Through intraoperative electrical stimulation mapping, it is possible to identify
      sites on the surface of the brain that are essential for language function.
      Interesting correlations have been found between the distribution of these sites
      and behavioral traits such as verbal IQ. In previous work, tools were developed
      for building a reconstruction of a patient's cortical surface and using it to
      recover coordinates of essential language sites. However, considerable expertise
      was required to produce good reconstructions. This paper describes an improved
      version of the mapping procedure, in which segmentation is driven by a 3-D shape
      model. The model-based approach provides more intuitive control over the system,
      allowing a trained user to complete a surface reconstruction and mapping in about
      two hours. This level of performance makes it feasible to gather language maps
      for a large number of patients, which hopefully will lead to significant new
      findings about language organization in the brain.

PMID- 9929354
TI  - Vector-field classification in magnetic-resonance angiography.
AB  - Phase-contrast magnetic-resonance angiography (PC MRA) generates images of
      vascular structures as three-dimensional maps of the blood-flow velocity in a
      volume of interest. To improve visualization methods for PC MRA, radiologists can
      benefit from image-processing algorithms that can classify flow and stationary
      tissue. In this paper, I describe a vector-difference distribution (VDD): a
      statistical model of noisy PC MRA that allows us to compute a measure of
      probability of flow for each voxel, based on the expected mixed distribution of
      flow and background samples. The estimates of flow probability form an image that
      can be used as a mask with, or as a surrogate for, the standard images for
      further processing and display. The implementation demonstrates that VDD (1) can
      classify probabilistically PC MRA images into flow and stationary tissue, and (2)
      can extract reliably first- and second-order statistical measures for flow and
      noise (background). A comparison of MIP images with and without a VDD-based
      probability mask demonstrates a 30-to-56-percent improvement in contrast-to-noise
      ratio.

PMID- 9929355
TI  - Locating blood vessels in retinal images by piece-wise threshold probing of a
      matched filter response.
AB  - We describe an automated method to locate and outline blood vessels in images of
      the ocular fundus. Such a tool should prove useful to eyecare specialists for
      purposes of patient screening, treatment evaluation, and clinical study. Our
      method differs from previously known methods in that it uses local and global
      vessel features cooperatively to segment the vessel network. A comparison of our
      method against hand-labeled ground truth segmentations of five images yielded 65%
      sensitivity and 81% specificity. A previously known technique yielded 69%
      sensitivity and 63% specificity. For a baseline, we also compared the ground
      truth against a second hand labeling, yielding 80% sensitivity and 90%
      specificity. These numbers indicate our method improves upon the previously known
      technique, but that further improvement is still possible.

PMID- 9929356
TI  - A new approach to optimal dynamic therapy planning.
AB  - Therapy planning is a very complex task. One of its crucial aspect is the
      derivation of therapeutic plans taking into account the dynamic aspect of the
      decision problem. This paper deals with dynamic decision problems using Influence
      Views, a novel graphical formalism based on Markov Decision Processes (MDPs)
      framework, in order to solve decision problems in which the optimal choice has to
      be revised periodically in accordance to the evolution of the patient's
      conditions. The proposed methodology has been applied to the plan of the
      prophylaxis in patients affected by a mild Hereditary Spherocytosis.

PMID- 9929357
TI  - Automatic query mapping among genomic databases: a pilot exploration.
AB  - As databases in the human genome project proliferate, it is important for users
      of one genomic database to identify similar or inconsistent data in other
      autonomously developed genomic databases. To do so, the user needs to issue the
      same query across multiple databases. We describe an approach that allows a query
      issued against one database to be automatically mapped to an equivalent query
      against another structurally different database. Our approach features two
      components: 1) a database designed to capture knowledge (metadata) that describes
      the correspondences among individual database components and 2) a module that
      utilizes the metadata to perform query mappings. As a demonstration, we apply our
      query mapping approach to two chromosome map databases (DB/12 and GDB).

PMID- 9929358
TI  - MHCWeb: converting a WWW database into a knowledge-based collaborative
      environment.
AB  - The World Wide Web (WWW) is useful for distributing scientific data. Most
      existing web data resources organize their information either in structured flat
      files or relational databases with basic retrieval capabilities. For databases
      with one or a few simple relations, these approaches are successful, but they can
      be cumbersome when there is a data model involving multiple relations between
      complex data. We believe that knowledge-based resources offer a solution in these
      cases. Knowledge bases have explicit declarations of the concepts in the domain,
      along with the relations between them. They are usually organized hierarchically,
      and provide a global data model with a controlled vocabulary. We have created the
      OWEB architecture for building online scientific data resources using knowledge
      bases. OWEB provides a shell for structuring data, providing secure and shared
      access, and creating computational modules for processing and displaying data. In
      this paper, we describe the translation of the online immunological database
      MHCPEP into an OWEB system called MHCWeb. This effort involved building a
      conceptual model for the data, creating a controlled terminology for the legal
      values for different types of data, and then translating the original data into
      the new structure. The OWEB environment allows for flexible access to the data by
      both users and computer programs.

PMID- 9929359
TI  - Integrating molecular diagnostic and flow cytometric reporting for improved
      longitudinal monitoring of HIV patients.
AB  - Studies have shown that monitoring HIV-infected patients undergoing
      antiretroviral therapy is best represented by combined measurement of plasma HIV
      1 RNA and CD4+ T-lymphocytes [1]. This pilot study at the University of Missouri
      Columbia integrates molecular diagnostic and flow cytometric data reporting to
      provide current and historical HIV-1 RNA levels and CD4+ T-cell counts. The
      development of a single database for storage and retrieval of these values
      facilitates composite report generation that includes longitudinal HIV-1 RNA
      levels and CD4+ T-cell counts for all patients. Results are displayed in tables
      and plotted graphically within a web browser. This method of data presentation
      converts individual data points to more useful medical information and could
      provide clinicians with decision support for improved monitoring of HIV patients
      undergoing antiretroviral therapy.

PMID- 9929360
TI  - Data mining by clinicians.
AB  - Clinical databases are becoming commonplace in healthcare environments. However,
      clinicians have been unable to readily explore these information sources, because
      currently available data retrieval tools require substantial technical skill, as
      well as knowledge of the underlying database structures. To address this, we have
      defined a group of "atomic" queries, including both population-based and temporal
      predicates, to enable the extraction of clinically meaningful information form
      these databases. DXtractor is an application that incorporates this
      functionality, and allows clinicians to simply combine these atomic queries. In
      doing so, arbitrarily complex data retrieval and exploration becomes possible for
      the non-programming clinician.

PMID- 9929372
TI  - Cardiac ryanodine receptor activity is altered by oxidizing reagents in either
      the luminal or cytoplasmic solution.
AB  - The location of reactive cysteine residues on the ryanodine receptor (RyR)
      calcium release channel was assessed from the changes in channel activity when
      oxidizing or reducing reagents were added to the luminal or cytoplasmic solution.
      Single sheep cardiac RyRs were incorporated into lipid bilayers with 10(-7) m
      cytoplasmic Ca2+. The thiol specific-lipophilic-4,4'-dithiodipyridine (4,4'-DTDP,
      1 mm), as well as the hydrophilic thimerosal (1 mm), activated and then inhibited
      RyRs from either the cis (cytoplasmic) or trans (luminal) solutions. Activation
      was associated with an increase in the (a) mean channel open time and (b) number
      of exponential components in the open time distribution from one ( approximately
      2 msec) to three (approximately 1 msec; approximately 7 msec; approximately 15
      msec) in channels activated by trans 4,4'-DTDP or cis or trans thimerosal. A
      longer component (approximately 75 msec) appeared with cis 4, 4'-DTDP. Activation
      by either oxidant was reversed by the thiol reducing agent, dithiothreitol. The
      results suggest that three classes of cysteines are available to 4,4'-DTDP or
      thimerosal, SHa or SHa* activating the channel and SHi closing the channel. SHa
      is either distributed over luminal and cytoplasmic RyR domains, or is located
      within the channel pore. SHi is also located within the transmembrane domain.
      SHa* is located on the cytoplasmic domain of the protein.

PMID- 9929373
TI  - ClC-2 activation modulates regulatory volume decrease.
AB  - ClC-2 belongs to a large family of chloride channels and its expression in
      certain cell types is associated with the appearance of swelling-activated
      chloride (Cl-) currents. In the present report, we examined the hypothesis that
      ClC-2 plays a role in regulatory volume decrease by expressing ClC-2 in Sf9 cells
      using the baculovirus system. First, we showed that ClC-2 protein expression is
      associated with appearance of a Cl- conductance which is activated by hypo
      osmotic shock and can be distinguished from swelling-activated chloride currents
      endogenous to Sf9 cells on the basis of its pharmacology and specific inhibition
      by an anti-ClC-2 antibody. Second, we show that the rate of regulatory volume
      decrease is significantly enhanced in Sf9 cells expressing ClC-2 protein. Hence,
      our data support the hypothesis that ClC-2 is capable of mediating regulatory
      volume decrease.

PMID- 9929374
TI  - Complement activation by bacterial surface glycolipids: a study with planar
      bilayer membranes.
AB  - Planar asymmetric glycolipid/phospholipid bilayer membranes were used as a
      reconstitution model of the lipid matrix of the outer membrane of Gram-negative
      bacteria to study complement (C) activation by various bacterial surface
      glycolipids with the aim of defining the C activation pathway. As glycolipids the
      lipopolysaccharides of Salmonella enterica serovar Minnesota R mutant strains
      R595 (Re LPS) and R4 (Rd2 LPS), pentaacyl lipid A from the LPS of the Escherichia
      coli Re mutant F515, and glycosphingolipid GSL-1 of Sphingomonas paucimobilis IAM
      12576 were used. Methylester and carboxyl-reduced derivatives of GSL-1 were used
      to elucidate the role of the carboxyl group as common functional group of LPS and
      GSL-1 for C activation. The formation of lytic pores was monitored via the
      measurement of changes in membrane current. For all glycolipids we observed a
      considerable increase in membrane current soon after addition of whole human
      serum due to the formation of lytic pores in the membranes. Pore formation was
      dependent on the presence of C9, indicating that the observed current changes
      were due to C activation. We found that in our reconstitution system of the outer
      membrane lipid A, Re LPS, and Rd2 LPS activated the classical pathway, the
      activation being independent of specific anti-LPS antibodies. In contrast, GSL-1
      and the methylester derivative of GSL-1 activated the alternative pathway even at
      the low serum concentrations used in this study (about 0.2% v/v). Interestingly,
      the carboxyl reduced GSL-1 activated the classical pathway.

PMID- 9929375
TI  - The effect of hemoglobin A and S on the volume- and pH-dependence of K-Cl
      cotransport in human erythrocyte ghosts.
AB  - K-Cl cotransport is abnormally active in erythrocytes containing positively
      charged hemoglobins such as Hb S (SS: beta6 Glu --> Val) or Hb C (CC: beta6 Glu -
      > Lys). The relatively younger age of erythrocytes in these diseases cannot
      completely account for the increased K-Cl cotransport activity. It has been
      suggested that these positively charged Hb may interact with the K-Cl cotransport
      system or one of its regulators and induce changes in its functional activity. We
      report here data on the volume- and pH-dependence of K-Cl cotransport in ghosts
      obtained from normal and sickle erythrocytes, and on the effect of addition of
      either Hb A or Hb S before resealing. In erythrocyte ghosts prepared with the gel
      column method to contain minimal amounts of Hb, (white ghosts, WG), K-Cl
      cotransport has similar magnitude in normal and sickle erythrocytes, is not
      inhibited by alkaline pH and it is volume-independent. Addition of low
      concentrations of Hb A to WG from normal erythrocytes decreases the magnitude of
      K-Cl cotransport and restores its volume dependency, but not its pH sensitivity.
      Addition of Hb S to WG from either normal or sickle erythrocytes restores the
      volume-dependent component of K-Cl cotransport and increases the magnitude of
      flux mediated by this transporter. Thus, Hb A and Hb S seem to affect in
      different manners the functional properties of K-Cl cotransport.

PMID- 9929376
TI  - Lipid-induced organization of a primary amphipathic peptide: a coupled AFM
      monolayer study.
AB  - To better understand the nature of the mechanism involved in the membrane uptake
      of a vector peptide, the interactions between dioleoylphosphatidylcholine and a
      primary amphipathic peptide containing a signal peptide associated with a nuclear
      localization sequence have been studied by isotherms analysis of mixed monolayers
      spread at the air-water interface. The peptide and the lipid interact through
      strong hydrophobic interactions with expansion of the mean molecular area that
      resulted from a lipid-induced modification of the organization of the peptide at
      the interface. In addition, a phase separation occurs for peptide molar fraction
      ranging from about 0.08 to 0.4 Atomic force microscopy observations made on
      transferred monolayers confirm the existence of phase separation and further
      reveal that mixed lipid-peptide particles are formed, the size and shape of which
      depend on the peptide molar fraction. At low peptide contents, round-shaped
      particles are observed and an increase of the peptide amount, simultaneously to
      the lipidic phase separation, induces morphological changes from bowls to
      filamentous particles. Fourier transform infrared spectra (FTIR) obtained on
      transferred monolayers indicate that the peptide adopts a beta-like structure for
      high peptide molar fractions. Such an approach involving complementary methods
      allows us to conclude that the lipid and the peptide have a nonideal miscibility
      and form mixed particles which phase separate.

PMID- 9929377
TI  - Differential transmembrane diffusion of triiodothyronine and thyroxine in
      liposomes: regulation by lipid composition.
AB  - How thyroid hormones move across biological or model membranes is a subject of
      controversy. The passage of the 3,5,3'triiodo l-thyronine and 3,5,3',5' tetraiodo
      l-thyronine across model membranes was evaluated by the addition of the hormones
      to liposomes containing 2, 4,6-trinitrobenzene sulfonic acid. Results indicate
      that hormones can react with an amino-reactive compound pre-encapsulated into
      phosphatidylcholine liposomes. The transversal motions of thyroid hormones were
      characterized by using physiological concentration levels of (125I) 3,5,3'triiodo
      l-thyronine and (125I) 3,5,3',5' tetraiodo l-thyronine. The hormone distribution
      between the two monolayers was time-dependent and kinetic data were fitted to a
      single exponential. Results obtained show that 3,5,3' triiodo l-thyronine can
      permeate phospholipid membranes and the diffusion time increases in the gel and
      liquid-ordered phase. On the contrary, 3,5,3', 5' tetraiodo l-thyronine could not
      diffuse the liposomal membrane from dimyristoyl and dipalmitoyl
      phosphatidylcholine in gel phase and egg yolk phosphatidylcholine:cholesterol in
      the liquid-ordered phase. Our results in the liquid-ordered phase suggest that
      diffusion movement of thyroid hormones across cell membranes depends on the
      amount of cholesterol in the bilayer.

PMID- 9929378
TI  - Kinetic differences in the phospholamban-regulated calcium pump when studied in
      crude and purified cardiac sarcoplasmic reticulum vesicles.
AB  - Phospholamban (PLN) phosphorylation contributes largely to the inotropic and
      lusitropic effects of beta-adrenergic agonists on the heart. The mechanical
      effects of PLN phosphorylation on the heart are generally attributed solely to an
      increase in the apparent affinity of the Ca pump in the sarcoplasmic reticulum
      (SR) membranes for Ca2+ with little or no effect on Vmax(Ca). In the present
      report, we compare the kinetic properties of the cardiac SR Ca pump in commonly
      studied crude microsomes with those of our recently developed preparation of
      light SR vesicles. We demonstrate that in crude microsomes, the increase in the
      apparent affinity of the pump for Ca2+ is larger, while the increase in Vmax(Ca)
      is smaller, than in purified vesicles. The greater phosphorylation-induced
      increase in apparent Ca2+ affinity in crude microsomes may be further enhanced by
      an ATP-sensitive inhibitory effect of ruthenium red on the activity of the pump
      at subsaturating, but not saturating, Ca2+ concentrations as a result of a
      greater inhibition in unphosphorylated microsomes. Upon increasing the ATP
      concentration from 1 to 5 mm, an inhibition by 10 micrometer ruthenium red is
      eliminated in phosphorylated microsomes and reduced in control microsomes.
      Addition of the phosphoprotein phosphatase inhibitor okadaic acid produces a
      considerable increase in the phosphorylation-induced effects in both crude and
      purified microsomes. We conclude that the use of purified cardiac SR vesicles is
      critical for the demonstration of a major increase in Vmax(Ca) in addition to an
      increase in the pump's apparent affinity for Ca2+ in response to phosphorylation
      of PLN by protein kinase A.

PMID- 9929379
TI  - Discontinuities in the temperature function of transmembrane water transport in
      Chara: relation to ion transport.
AB  - The NMR (nuclear magnetic resonance) method of Conlon and Outhred (1972) was used
      to measure diffusional water permeability of the nodal cells of the green alga
      Chara gymnophylla. Two local minima at 15 and 30 degreesC of diffusional water
      permeability (Pd) were observed delimiting a region of low activation energy (Ea
      around 20 kJ/mol) indicative of an optimal temperature region for membrane
      transport processes. Above and below this region water transport was of a
      different type with high Ea (about 70 kJ/mol). The triphasic temperature
      dependence of the water transport suggested a channel-mediated transport at 15-30
      degreesC and lipid matrix-mediated transport beyond this region. The K+ channel
      inhibitor, tetraethylammonium as well as the Cl- channel inhibitor, ethacrynic
      acid, diminished Pd in the intermediate temperature region by 54 and 40%,
      respectively. The sulfhydryl agent p-(chloromercuri-benzensulfonate) the water
      transport inhibitor in erythrocytes also known to affect K+ transport in Chara,
      only increased Pd below 15 degreesC. In high external potassium ('K-state') water
      transport minima were pronounced. The role of K+ channels as sensors of the
      optimal temperature limits was further emphasized by showing a similar triphasic
      temperature dependence of the conductance of a single K+ channel also known to
      cotransport water, which originated from cytoplasmic droplets (putatively
      tonoplast) of C. gymnophylla. The minimum of K+ single channel conductance at
      around 15 degreesC, unlike the one at 30 degreesC, was sensitive to changes of
      growth temperature underlining membrane lipid involvement. The additional role of
      intracellular (membrane?) water in the generation of discontinuities in the above
      thermal functions was suggested by an Arrhenius plot of the cellular water
      relaxation rate which showed breaks at 13 and 29 degreesC.

PMID- 9929380
TI  - Accelerated evolution and molecular surface of venom phospholipase A2 enzymes.
AB  - Multiple phospholipase A2 (PLA2) isoenzymes found in a single snake venom induce
      a variety of pharmacological effects. These multiple forms are formed by gene
      duplication and accelerated evolution of exons. We examined the amino acid
      sequences of 127 snake venom PLA2 enzymes and their homologues to study in which
      location most natural substitutions occur. Our data show that hot spots of amino
      acid substitutions in this group of proteins occur mostly on the surface. A
      logistic model correlating the substitution rates of each amino acid residue with
      their surface accessibility indicates that the probability of natural
      substitutions occurring in the fully exposed residue is 2.6-3.5 times greater
      than that of substitutions occurring in buried residues. These surface
      substitutions play a significant role in the evolution of new PLA2 isoenzymes by
      altering the specificity of targeting to various tissues or cells, resulting in
      distinct pharmacological effects. Thus natural substitutions in PLA2 enzymes, in
      contrast to popular belief, are not random substitutions but appear to be
      directed toward modifying the molecular surface.

PMID- 9929381
TI  - Relationships between transcriptional and translational control of gene
      expression in Saccharomyces cerevisiae: a multiple regression analysis.
AB  - Natural selection for an increased translation efficiency has been proposed as
      the main determinant for the bias in codon usage observed in many genes of
      Saccharomyces cerevisiae. Recently, the efficiency of transcription of a large
      number of yeast genes has been determined, based on the cellular content of the
      respective mRNAs: this provides an additional dimension to the study of the
      multisep process of gene expression. Using a representative set of yeast genes
      with a known level of transcription, the relationship between transcriptional and
      translational steps was evaluated by a multiple linear regression model. This
      analysis demonstrated a positive correlation between the amount of transcript,
      given as the number of mRNA copies per cell for each individual gene, and indices
      evaluating the effects of translational selection on the corresponding codon
      usage pattern. This finding suggests a close association of the cellular mRNA
      content, regulated also at the transcriptional level, to its efficiency of
      translation, mediated by a fine-tuning of codon usage strategy. Moreover,
      multiple regression analysis demonstrated that the transcription level of a gene
      can be approximately predicted using indices of bias deriving from its nucleotide
      sequence. This allowed for an extensive investigation of uncharacterized regions
      of the complete genome sequence of S. cerevisiae, to detect new potential short
      protein coding genes that were not considered by previous searching procedures.
      Several small open reading frames exhibiting a statistically significant coding
      potential were thus identified as good candidates for functional analysis.

PMID- 9929382
TI  - Physical and genetic map of the genome of Buchnera, the primary endosymbiont of
      the pea aphid Acyrthosiphon pisum.
AB  - The genome of Buchnera, an endosymbiotic bacterium of the pea aphid Acyrthosiphon
      pisum, was characterized by pulse-field gel electrophoresis (PFGE) as a circular
      DNA molecule of 657 kb. The enzymes I-CeuI, CpoI, ApaI, SmaI, NaeI, SacII, MluI,
      FspI, and NruI were used to cleave the DNA of Buchnera into fragments of suitable
      size for PFGE analysis. A physical map of the Buchnera genome, including
      restriction fragments from seven of these enzymes, was constructed using double
      cutting, partial digestion, and hybridization with linking fragments, and 29
      genes and operons were localized on the map. In addition, the genomic map of
      Buchnera was compared with those of Escherichia coli and Haemophilus influenzae.
      The gene order in Buchnera is more similar to that of E. coli than to H.
      influenzae. The dramatic shrinkage of the Buchnera genome compared with those of
      other members of the closely related Enterobacteriaceae family is discussed in
      terms of evolution under the influence of the intracellular symbiotic
      association.

PMID- 9929383
TI  - The members of the RH gene family (RH50 and RH30) followed different evolutionary
      pathways.
AB  - The evolution of the RH gene family is characterized by two major duplication
      events, the first one originating the RH50 and RH30 genes and the second one
      giving rise to RHCE and RHD, the two paralogous RH30 genes which encode the Rh
      blood group antigens in human. The new sequence data obtained here for mouse RH50
      and RH30 and for macaque RH50 allowed us to compare the evolutionary rates of the
      two genes and to show that RH50 evolved about 2.6 times more slowly than RH30 at
      nonsynonymous positions. This result implies that Rh50 proteins were
      evolutionarily more conserved compared to Rh30 polypeptides, thus being
      indicative of the functional significance of the former protein in species as
      distantly related as sponge and human. The duplication event leading to RH50 and
      RH30 genes was estimated to have occurred between 250 and 346 million years ago.
      Moreover, we could also estimate that the duplication event producing the RHCE
      and RHD genes occurred some 8.5 +/- 3.4 million years ago, in the common ancestor
      of human, chimpanzee, and gorilla. Interestingly, this event seems to coincide
      with the appearance in these species of a G-to-T mutation in the RH50 gene which
      created a stop codon in the corresponding transcript. This led to an Rh50 C
      terminal cytoplasmic domain shorter than that found in orangutan and early
      primates.

PMID- 9929384
TI  - The dentin matrix protein 1 gene of prototherian and metatherian mammals.
AB  - Mineralization of tooth dentin (the deposition of hydroxyapatite crystals in and
      around collagen type I fibers of the extracellular matrix) requires the
      involvement of several genes, among them the gene coding for the dentin matrix
      protein 1, DMP1. We determined the exon-intron organization of the cattle DMP1
      gene and used this information to amplify by the polymerase chain reaction
      homologous gene fragments from the genomic DNA of two species of metatherian
      (marsupial) mammals and one prototherian (monotreme) species. The translated
      proto- and metatherian protein sequences are highly divergent from the eutherian
      sequences but retain the general characteristics of the DMP1 (high acidity,
      serine-richness, multiple glycosylation sites, and the presence of the RGD cell
      attachment tripeptide). They therefore appear to be functional even though,
      evolutionarily, teeth are in a regression phase in prototherians. It is possible,
      therefore, that DMP1 is also involved in other functions besides dentinogenesis.
      The DMP1 gene appears to evolve rapidly and apparently tolerates non-frame
      shifting insertions/deletions throughout the coding sequence.

PMID- 9929385
TI  - Relationships among isoacceptor tRNAs seems to support the coevolution theory of
      the origin of the genetic code.
AB  - A new method for looking at relationships between nucleotide sequences has been
      used to analyze divergence both within and between the families of isoaccepting
      tRNA sets. A dendrogram of the relationships between 21 tRNA sets with different
      amino acid specificities is presented as the result of the analysis. Methionine
      initiator tRNAs are included as a separate set. The dendrogram has been
      interpreted with respect to the final stage of the evolutionary pathway with the
      development of highly specific tRNAs from ambiguous molecular adaptors. The
      location of the sets on the dendrogram was therefore analyzed in relation to
      hypotheses on the origin of the genetic code: the coevolution theory, the
      physicochemical hypothesis, and the hypothesis of ambiguity reduction of the
      genetic code. Pairs of 16 sets of isoacceptor tRNAs, whose amino acids are in
      biosynthetic relationships, occupied contiguous positions on the dendrogram, thus
      supporting the coevolution theory of the genetic code.

PMID- 9929386
TI  - Horizontal gene transfer involved in the convergent evolution of the plasmid
      encoded enantioselective 6-hydroxynicotine oxidases.
AB  - The D- and L-specific nicotine oxidases are flavoproteins involved in the
      oxidative degradation of nicotine by the Gram-positive soil bacterium
      Arthrobacter nicotinovorans. Their structural genes are located on a 160-kbp
      plasmid together with those of other nicotine-degrading enzymes. They are
      structurally unrelated at the DNA as well as at the protein level. Each of these
      oxidases possesses a high degree of substrate specificity; their catalytic
      stereoselectivity is absolute, although they are able to bind both enantiomeric
      substrates with a similar affinity. It appears that the existence of these
      enzymes is the result of convergent evolution. The amino acid sequence of 6
      hydroxy-l-nicotine oxidase (EC 1.5.3.6) as derived from the respective structural
      gene shows considerable structural similarity with eukaryotic monoamine oxidases
      (EC 1.4.3.4) but not with monoamine oxidases from prokaryotic bacteria including
      those of the genus Arthrobacter. These similarities are not confined to the
      nucleotide-binding sites. A 100-amino acid stretch at the N-terminal regions of 6
      hydroxy-l-nicotine oxidase and human monoamine oxidases A possess a 35% homology.
      Overall, 27.0, 26.9, and 25.8% of the amino acid positions of the monoamine
      oxidases of Aspergillus niger (N), humans (A), and rainbow trout (Salmo
      gairdneri) are identical to those of 6-hydroxy-l-nicotine oxidase (Smith-Waterman
      algorithm). In addition, the G+C content of the latter enzyme is in the range of
      that of eukaryotic monoamine oxidases and definitely lower than that of the A.
      nicotinovorans DNA and even that of the pAO1 DNA. The primary structure of 6
      hydroxy-d-nicotine oxidase (EC 1.5.3.5) does not reveal its evolutionary history
      as easily. Significant similarities are found with a mitomycin radical oxidase
      from Streptomyces lavendulae (23.3%) and a "hypothetical protein" from
      Mycobacterium tuberculosis (26.0%). It is proposed that the plasmid-encoded gene
      of 6-hydroxy-l-nicotine oxidase evolved after horizontal transfer from an
      eukaryotic source.

PMID- 9929387
TI  - Dynamic diversification from a putative common ancestor of scorpion toxins
      affecting sodium, potassium, and chloride channels.
AB  - Scorpions have survived successfully over millions of years without detectable
      changes in their morphology. Instead, they have developed an efficient alomonal
      machinery and a stinging device supporting their needs for prey and defense. They
      produce a large variety of polypeptidic toxins that bind and modulate ion channel
      conductance in excitable tissues. The binding site, mode of action, and chemical
      properties of many toxins have been studied extensively, but little is known
      about their genomic organization and diversity. Genes representing each of the
      major classes of Buthidae scorpion toxins, namely, "long" toxins, affecting
      sodium channels (alpha, depressant, and excitatory), and "short" toxins,
      affecting potassium and chloride channels, were isolated from a single scorpion
      segment and analyzed. Each toxin type was found to be encoded by a gene family.
      Regardless of toxin length, 3-D structure, and site of action, all genes contain
      A+T-rich introns that split, at a conserved location, an amino acid codon of the
      signal sequence. The introns vary in length and sequence but display identical
      boundaries, agree with the GT/AG splice junctions, and contain T-runs downstream
      of a putative branch point, 5'-TAAT-3'. Despite little sequence similarity among
      all toxin classes, the conserved gene organization, intron features, and common
      cysteine-stabilized alpha-helical (CSH) core connecting an alpha-helix to a three
      stranded beta-sheet suggest, that they all evolved from an ancestral common
      progenitor. Furthermore, the vast diversity found among genomic copies, cDNAs,
      and their protein products for each toxin suggests an extensive evolutionary
      process of the scorpion "pharmaceutical factory," whose success is due, most
      likely, to the inherent permissiveness of the toxin exterior to structural
      alterations.

PMID- 9929388
TI  - Molecular phylogeny of phi29-like phages and their evolutionary relatedness to
      other protein-primed replicating phages and other phages hosted by gram-positive
      bacteria.
AB  - The phi29-like phage genus of Podoviridae family contains phages B103, BS32, GA
      1, M2, Nf, phi15, phi29, and PZA that all infect Bacillus subtilis. They have
      very similar morphology and their genomes consist of linear double-stranded DNA
      of approximately 20 kb. The nucleotide sequences of individual genomes or their
      parts determined thus far show that these phages evolved from a common ancestor.
      A terminal protein (TP) that is covalently bound to the DNA 5'-end primes DNA
      replication of these phages. The same mechanism of DNA replication is used by the
      Cp-1 related phages (also members of the Podoviridae family) and by the phage
      PRD1 (member of the Tectoviridae family). Based on the complete or partial
      genomic sequence data of these phages it was possible to analyze the evolutionary
      relationship within the phi29-like phage genus as well as to other protein-primed
      replicating phages. Noncoding regions containing origins of replication were used
      in the analysis, as well as amino acid sequences of DNA polymerases, and with the
      phi29-like phages also amino acid sequences of the terminal proteins and of the
      gene 17 protein product, an accessory component of bacteriophage DNA replicating
      machinery. Included in the analysis are also results of a comparison of these
      phage DNAs with the prophages present in the Bacillus subtilis genome. Based on
      this complex analysis we define and describe in more detail the evolutionary
      branches of phi29-like phages, one branch consisting of phages BS32, phi15,
      phi29, and PZA, the second branch composed of phages B103, M2, and Nf, and the
      third branch having phage GA-1 as its sole member. In addition, amino acid
      sequences of holins, proteins involved in phage lysis were used to extend the
      evolutionary study to other phages infecting Gram-positive bacteria. The analysis
      based on the amino acid sequences of holins showed several weak points in present
      bacteriophage classification.

PMID- 9929389
TI  - Synonymous and nonsynonymous substitution rates in diatoms: a comparison between
      chloroplast and nuclear genes.
AB  - Rates of synonymous and nonsynonymous nucleotide substitutions and codon usage
      bias (ENC) were estimated for a number of nuclear and chloroplast genes in a
      sample of centric and pennate diatoms. The results suggest that DNA evolution has
      taken place, on an average, at a slower rate in the chloroplast genes than in the
      nuclear genes: a rate variation pattern similar to that observed in land plants.
      Synonymous substitution rates in the chloroplast genes show a negative
      association with the degree of codon usage bias, suggesting that genes with a
      higher degree of codon usage bias have evolved at a slower rate. While this
      relationship has been shown in both prokaryotes and multicellular eukaryotes, it
      has not been demonstrated before in diatoms.

PMID- 9929390
TI  - On negative selection against ATG triplets near start codons in eukaryotic and
      prokaryotic genomes.
AB  - The frequencies of ATG triplets in the genomes of various species were
      systematically analyzed, and the frequency of ATG triplets was significantly low
      around start codons in both prokaryotic and eukaryotic genomes. In eukaryotes,
      however, the frequency decrease before the start codon is much more evident than
      that after the start codon. In prokaryotes, on the other hand, the ATG frequency
      pattern around the start codon is less evident, and-more importantly-symmetric.
      We also computed average distances between a start codon and its nearest upstream
      located ATG triplet and found a general tendency for the average distances to be
      longer in higher organisms.

PMID- 9929391
TI  - Phylogeny of organisms investigated by the base-pair changes in the stem regions
      of small and large ribosomal subunit RNAs.
AB  - In order to obtain the evolutionary distance data that are as purely additive as
      possible, we have developed a novel method for evaluating the evolutionary
      distances from the base-pair changes in stem regions of ribosomal RNAs (rRNAs).
      The application of this method to small-subunit (SSU) and large-subunit (LSU)
      rRNAs provides the distance data, with which both the unweighted pair group
      method of analysis and the neighbor-joining method give almost the same tree
      topology of most organisms except for some Protoctista, thermophilic bacteria,
      parasitic organisms, and endosymbionts. Although the evolutionary distances
      calculated with LSU rRNAs are somewhat longer than those with SSU rRNAs, the
      difference, probably due to a slight difference in functional constraint, is
      substantially decreased when the distances are converted into the divergence
      times of organisms by the measure of the time scale estimated in each type of
      rRNAs. The divergence times of main branches agree fairly well with the
      geological record of organisms, at least after the appearance of oxygen-releasing
      photosynthesis, although the divergence times of Eukaryota, Archaebacteria, and
      Eubacteria are somewhat overestimated in comparison with the geological record of
      Earth formation. This result is explained by considering that the mutation rate
      is determined by the accumulation of misrepairs for DNA damage caused by
      radiation and that the effect of radiation had been stronger before the oxygen
      molecules became abundant in the atmosphere of the Earth.

PMID- 9929392
TI  - The plastid genome of the cryptophyte alga, Guillardia theta: complete sequence
      and conserved synteny groups confirm its common ancestry with red algae.
AB  - The plastid genome of the cryptophyte alga Guillardia theta (121,524 bp) has been
      completely sequenced. The genome is 33% G+C and contains a short, nonidentical
      inverted repeat (4.9 kb) encoding the two rRNA cistrons. The large and small
      single-copy regions are 96.3 and 15.4 kb, respectively. Forty-six genes encoding
      proteins for photosynthesis, 5 genes for biosynthetic function, 5 genes involved
      in replication and division, 30 tRNA genes, 44 ribosomal protein genes (26 large
      subunit and 18 small subunit), 3 translation factors, 8 genes encoding components
      of the transcriptional machinery including 3 ycfs (hypothetical chloroplast
      frames), and 26 additional ycfs have been identified. There are eight ORFs larger
      than 50 amino acids, 3 of which have homologues on the plastid genome of the
      rhodophyte, Porphyra purpurea (Reith and Munholland 1995) and/or the
      Synechocystis genome (Kaneko et al. 1996) and can be designated new ycfs.
      Intergenic spacers are very short, no introns have been detected, and several
      genes overlap, all resulting in a very compact genome. In addition, large
      clusters of genes (such as those for the ribosomal proteins) are organized into
      single transcriptional units (Wang et al. 1997), again resulting in an
      economically organized genome. The cryptophyte plastid genome is almost
      completely comprised of clusters of genes that are found on the rhodophyte
      Porphyra purpurea, confirming its common ancestry with red algae. Furthermore,
      recombination events involving both tRNA genes and the rRNA cistrons appear to
      have been responsible for the structure of the cryptophyte plastid genome,
      including the formation of the inverted repeat.

PMID- 9929393
TI  - Microsatellite allele size homoplasy in the guppy (Poecilia reticulata)

PMID- 9929395
TI  - Evolution of a mammalian promoter through changes in patterns of transcription
      factor binding 

PMID- 9929394
TI  - The long terminal repeat of an endogenous retrovirus induces alternative splicing
      and encodes an additional carboxy-terminal sequence in the human leptin receptor.
AB  - The evolution of mammalian protein structure and regulation, specifically
      transcriptional and posttranscriptional regulation, may include among its tools
      the use of abundant retroviral long terminal repeats (LTRs). In particular, LTRs
      may be turned into switches for alternative splicing. This type of regulatory
      pathway is illustrated by the alternative splicing in the human leptin receptor
      (OBR). The human leptin receptor is involved in the control of important
      biological processes including energy expenditure, production of sex hormones,
      and activation of hemopoietic cells. OBRa and OBRb are the two major,
      alternatively spliced forms of the leptin receptor, called the "short form" and
      the "long form," respectively. We report that the OBRa short form is the result
      of a double splicing event which occurs within the LTR of the endogenous
      retrovirus HERV-K. Working as a switch of alternative splicing, this LTR also
      encodes the terminal 67 amino acid residues in OBRa. We suggest the possibility
      of transcriptional and posttranscriptional regulation of OBR expression by
      steroids that bind the LTR.

PMID- 9929396
TI  - Identification of Culturable Oligotrophic Bacteria within Naturally Occurring
      Bacterioplankton Communities of the Ligurian Sea by 16S rRNA Sequencing and
      Probing.
AB  - > Abstract Typical marine bacteria (i.e., obligately oligotrophic) that were
      numerically dominant members of naturally occurring marine communities were
      identified by cloning and sequencing the amplified 16S rRNA genes obtained from
      dilution cultures of the original samples. The data reported here refer to two
      different habitats of a marine pelagic environment (28 miles offshore, in the
      northwestern Mediterranean Sea). The samples were taken from the water column at
      two representative layers, i.e., the 30-m depth, corresponding to the chlorophyll
      maximum layer, and the 1800-m depth, representative of a deep, oligotrophic
      environment. Three major lineages were found in the 16S rDNA clone libraries
      prepared from the two samples, two of which could be assigned to the Vibrio and
      the Rhodobacter groups. The third lineage was a distant relative of the genus
      Flavobacterium, but it was not closely related to any marine isolate. Six
      oligonucleotide probes, either complementary to the conserved sequence domains or
      selectively hybridizing to the clone sequences, were designed for use as
      hybridization group-specific and strain-specific probes. A single-mismatch
      discrimination between certain probes and nontarget sequences was demonstrated by
      detecting the probes' specificity at different hybridization and washing
      conditions. The screening of the clone libraries with the obtained probes
      revealed that neither the 30-m sample higher dilution nor the 1800-m one were
      pure cultures. While some representatives of the Vibrio group were found in both
      the surface and the deep sample, the members of the Flavobacterium and
      Rhodobacter lineages were detected only in the deep and the euphotic layers,
      respectively. We suggest an approach for analyzing autochthonous marine bacteria
      able to grow in unamended seawater.

PMID- 9929397
TI  - Growth Rates of Marine Bacterial Isolates on Particulate Organic Substrates
      Solubilized by Freely Released Extracellular Enzymes.
AB  - > Abstract Growth rates of marine bacterial isolates on particulate organic
      substrates were measured using a novel apparatus which restricts bacterial cells
      to the uptake of hydrolysate produced from particulate substrates only by enzymes
      that are actively released from the bacterium into the culture medium.
      Significant, varying growth rates were measured for four different marine
      bacteria, using three different, ecologically significant particulate organic
      substrates (preparations of amylopectin, chitin, and animal hide). Growth rates
      sometimes approached but were usually lower than rates that have been reported in
      laboratory experiments using dissolved organic growth substrates. These results
      are consistent with recent model predictions and have important implications for
      microbial ecology and material cycling in diverse liquid-bathed environments.

PMID- 9929398
TI  - Protozoan Bacterivory in the Ice and the Water Column of a Cold Temperate Lagoon.
AB  - > Abstract Bacterial abundance and bacterivorous protist abundance and activity
      were examined in ice-brine and water column communities of a cold temperate
      Japanese lagoon (Saroma-Ko Lagoon, Hokkaido, 44 degreesN, 144 degreesE), during
      the late winter phase of ice community development (February-March 1992).
      Bacterial abundance averaged 6 and 1 x 10(5) cells ml-1 in the ice-brine and
      plankton samples, respectively, and generally decreased during the sampling
      period. Bacterivorous protists, identified based on direct observation of short
      term (<1 h) ingested fluorescently labeled bacteria (FLB) in their food vacuoles,
      were largely dominated by flagellates, mainly cryothecomonad-type and chrysomonad
      like cells and small dinoflagellates of the genus Gymnodinium. Bacterivorous
      ciliates included mainly the prostomatid Urotricha sp., the scuticociliates
      Uronema and Cyclidium, the choreotrichs Lohmaniella oviformis and Strobilidium,
      and the hypotrich Euplotes sp. Protist abundance averaged 4 x 10(3) and 8.1 cells
      ml-1 in the ice-brine and 0.3 x 10(3) and 1.2 cells ml-1 in the plankton, for
      flagellates and ciliates, respectively. In contrast to bacteria, the abundance of
      protists generally increased throughout the sampling period, indicating predator
      prey interactions. Protistan bacterivory, measured from the rate of FLB
      disappearance over 24 h, averaged 36% (ice) and 24% (plankton) of bacterial
      standing stock and exhibited the same seasonal pattern as for protist abundance.
      The calculated specific clearance (range, 2-67 nl protozoa-1 h-1) and ingestion
      (<1-26 particles protozoa-1 h-1) rates were likely to be minimal estimates and
      grazing impact may have been higher on occasion. Indications for the dependence
      of "bacterivorous protists" on nonbacterial food items were also provided.
      Although alternative sources of bacterial loss are likely to be of importance,
      this study provides evidence for the potential of protozoan assemblages as
      bacterial grazers in both sea ice-brine biota and water column at the southern
      limit of sea ice in the northern hemisphere.

PMID- 9929399
TI  - Growth of Amoebae and Flagellates on Bacteria Deposited on Filters.
AB  - > Abstract Artificial bacterial biofilms were formed by making microwave
      irradiated, dual-radioisotope-labelled Vibrio bacteria adhere to 0.4 um pore size
      filters with albumin. The rate of release of 3H from thymidine label in these
      bacteria into the surrounding seawater when protozoa were incubated with the
      biofilm indicated the predator's grazing rate, and the rate of accumulation of
      14C in the predators from leucine label in the bacteria indicated the
      assimilation rate of the protozoa. The amoeba Vanella septentrionalis consumed
      about 60% of the available bacteria between the 5th and 15th days of incubation
      with a gross growth efficiency of 22 +/- 6%, compared with about 75% consumption
      at 29 +/- 8% efficiency for the surface-feeding flagellate Caecitellus parvulus,
      and about 55% consumption at 16 +/- 5% efficiency for the suspension-feeding
      flagellate Pteridomonas danica. As a result of their grazing and metabolism these
      protozoa regenerated about 70-85% of the nutrients present in their food and
      released these nutrients in the immediate vicinity of the bacterial biofilm. The
      biomass of the amoeba Vanella was calculated to be 166 pg protein cell-1 during
      maximum growth and 93 pg protein cell-1 in the stationary phase.

PMID- 9929400
TI  - Moving Waves of Bacterial Populations and Total Organic Carbon along Roots of
      Wheat.
AB  - > Abstract To determine if spatial variation in soluble carbon sources along the
      root coincides with different trophic groups of bacteria, copiotrophic and
      oligotrophic bacteria were enumerated from bulk soil and rhizosphere samples at 2
      cm intervals along wheat roots 2, 3, and 4 weeks after planting. There was a
      moderate rhizosphere effect in one experiment with soil rich in fresh plant
      debris, and a very pronounced rhizosphere effect in the second experiment with
      soil low in organic matter. We obtained wavelike patterns of both trophic groups
      of bacteria as well as water-soluble total organic carbon (TOC) along the whole
      root length (60 or 90 cm). TOC concentrations were maximal at the root tip and
      base and minimal in the middle part of the roots. Oscillations in populations of
      copiotrophic and oligotrophic bacteria had two maxima close to the root tip and
      at the root base, or three maxima close to the tip, in the middle section, and at
      the root base. The location and pattern of the waves in bacterial populations
      changed progressively from week to week and was not consistently correlated with
      TOC concentrations or the location of lateral root formation. Thus, the
      traditional view that patterns in bacterial numbers along the root directly
      reflect patterns in exudation and rhizodeposition from several fixed sources
      along the root may not be true. We attributed the observed wavelike patterns in
      bacterial populations to bacterial growth and death cycles (due to autolysis or
      grazing by predators). Considering the root tip as a moving nutrient source,
      temporal oscillations in bacterial populations at any location where the root tip
      passed would result in moving waves along the root. This change in concept about
      bacterial populations in the rhizosphere could have significant implications for
      plant growth promotion and bioremediation.

PMID- 9929401
TI  - Comparison of Parental and Transgenic Alfalfa Rhizosphere Bacterial Communities
      Using Biolog GN Metabolic Fingerprinting and Enterobacterial Repetitive
      Intergenic Consensus Sequence-PCR (ERIC-PCR).
AB  - > Abstract Rhizosphere bacterial communities of parental and two transgenic
      alfalfa (Medicago sativa L.) of isogenic background were compared based on
      metabolic fingerprinting using Biolog GN microplates and DNA fingerprinting of
      bacterial communities present in Biolog GN substrate wells by enterobacterial
      repetitive intergenic consensus sequence-PCR (ERIC-PCR). The two transgenic
      alfalfa expressed either bacterial (Bacillus licheniformis) genes for alpha
      amylase or fungal (Phanerochaete chrysosporium) genes for Mn-dependent lignin
      peroxidase (Austin S, Bingham ET, Matthews DE, Shahan MN, Will J, Burgess RR,
      Euphytica 85:381-393). Cluster analysis and principal components analysis (PCA)
      of the Biolog GN metabolic fingerprints indicated consistent differences in
      substrate utilization between the parental and lignin peroxidase transgenic
      alfalfa rhizosphere bacterial communities. Cluster analysis of ERIC-PCR
      fingerprints of the bacterial communities in Biolog GN substrate wells revealed
      consistent differences in the types of bacteria (substrate-specific populations)
      enriched from the rhizospheres of each alfalfa genotype. Comparison of ERIC-PCR
      fingerprints of bacterial strains obtained from substrate wells to substrate
      community ERIC-PCR fingerprints suggested that a limited number of populations
      were responsible for substrate oxidation in these wells. Results of this study
      suggest that transgenic plant genotype may affect rhizosphere microorganisms and
      that the methodology used in this study may prove a useful approach for the
      comparison of bacterial communities.

PMID- 9929402
TI  - Degradation of Soil Humic Extract by Wood- and Soil-Associated Fungi, Bacteria,
      and Commercial Enzymes.
AB  - > Abstract An alkaline humic extract (HE) of a black calcareous forest mull was
      exposed to 36 fungal and 9 eubacterial isolates in liquid standing culture. At 21
      d in fungi, and 4 d in bacteria, the groups of wood-degrading basidiomycetes,
      terricolous basidiomycetes, ectomycorrhizal fungi, soil-borne microfungi, and
      eubacteria had reduced the absorbance (A340) of HE media by 57, 28, 19, 26 and
      5%, respectively. Gel permeation chromatography revealed that the large humic
      acid molecules were more readily degraded than the smaller fulvic acid molecules
      and served as a sole source of carbon and energy. The more active HE degraders
      reduced the overall molecular weight of humic and fulvic acids by 0.25 to 0.47
      kDa. They also reduced the chemical reactivity of HE to tetrazotized o
      dianisidine, indicating the degradation of hydroxylated aromatic molecules (which
      are responsible for this reaction). Decreases in absorbance, molecular weight,
      and reactivity were caused by fungal manganese peroxidase, horseradish
      peroxidase, beta-glucosidase, and abiotic oxidants such as H2O2 and Mn(III)
      acetate. It is concluded that fungi, some of which are propagated in contaminated
      soils to control xenobiotics, metabolize HE compounds enzymatically. They use
      enzymes which are also involved in the degradation of soil xenobiotics. Because
      of reductions in the molecular weight of HE, which is a potential carrier of
      heavy metal ions and xenobiotics, solubility and motility of humic substances in
      soil and surface waters are increased.

PMID- 9929403
TI  - Effect of Crude Oil and Chemical Additives on Metabolic Activity of Mixed
      Microbial Populations in Fresh Marsh Soils.
AB  - > Abstract Hydrocarbons increase abundance of hydrocarbon-degrading
      microorganisms, but also decrease microbial diversity. This could disrupt
      ecosystem dynamics by altering soil organic matter mineralization and resultant
      nutrient remineralization rates. Crude oil, which is known to contain toxins and
      reduce microbial diversity, was hypothesized to reduce gross metabolic activity
      of mixed microbial populations in wetland soils. Soil respiration and Eh were
      compared, for 6 months, among microcosms containing marsh soils that differed in
      soil organic matter (Panicum hemitomon Shult. or Sagittaria lancifolia L.
      dominated marshes), crude oil (Arabian crude, Louisiana crude, or no oil), and
      additives (a cleaner, a dispersant, fertilizer, or no additive). No treatment
      slowed activity; instead, Louisiana plus fertilizer and all Arabian treatments
      temporarily accelerated activity. Additional C respired from oiled microcosms
      exceeded C added as crude oil by 1.4 to 3.5 times. Thus, much additional C
      originated from soil organic matter rather than crude oil. Crude oils temporarily
      lowered soil Eh, which is consistent with accelerated metabolism and demand for
      electron acceptors. The lack of inhibition observed at the community level does
      not necessarily indicate an absence of toxicity. Instead, tolerant species with
      metabolic versatility probably maintained activity. Stimulation probably resulted
      from removal of micronutrient limitation, rather than removal of grazing pressure
      or macronutrient limitation. Regardless, accelerated soil organic matter
      mineralization surely accelerated nutrient remineralization. This might explain
      some reports of crude oil stimulating plant growth. These results are not
      inconsistent with theoretical and experimental conclusions regarding effects of
      biodiversity on ecosystem stability and productivity, nor are they inconsistent
      with conclusions that crude oils contain components that are toxic to microbes,
      vegetation, and fauna. However, these data do indicate that crude oils also
      contain components that temporarily stimulate metabolic activity of surviving
      microbes.

PMID- 9929404
TI  - Non-invasive estimation of pulmonary arterial hypertension in chronic obstructive
      pulmonary disease.
AB  - The feasibility and reliability of the combination of several noninvasive methods
      using a multivariate method of analysis to predict pulmonary artery hypertension
      (PAH) is evaluated in 20 patients with chronic obstructive pulmonary disease.
      These methods comprised arterial blood gases (Pao2, Paco2), pulmonary functional
      parameters (FEV1), echo-Doppler parameters (tricuspid regurgitation jets,
      acceleration time on pulmonary valve), computed tomography measurements
      (transhilar distance, hilar thoracic index, and measurement of the descending
      branch of the right pulmonary artery to the lower lobe). A multiple stepwise
      regression analysis (including one Doppler parameter, two parameters of arterial
      blood gases, and one functional parameter) revealed a coefficient of
      determination (R2) equal to 0.954 for mean pulmonary artery pressure (MPAP) with
      a standard error of estimate (S.E.E.) of 5.25 mmHg. A stepwise regression
      analysis including computed tomography and radiographic parameters revealed an R2
      equal to 0.970 for PAP with a S.E.E. of 4.26 mmHg. Logistical regression analysis
      classified correctly 80% of patients with PAH using noninvasive methods such as
      the diameter of the main pulmonary artery and the diameter of the left pulmonary
      arterial branch calculated by computed tomography. Not only the presence of PAH
      but also the level of MPAP can be estimated by the combination of multiple
      stepwise and logistical regression analyses.

PMID- 9929405
TI  - Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by
      monocrotaline in rats.
AB  - The effect of administering prostaglandin E1 (PGE1) on the extent of
      monocrotaline (MCT)-induced pulmonary hypertension and cytokine production
      [interleukins (IL) 1 and 6 and tumor necrosis factor (TNF)] by macrophages during
      MCT induction of pulmonary hypertension was studied. Right ventricle/left
      ventricle plus septum weight ratios (RV/LV + S) were used as an index of the
      development of pulmonary hypertension. Administering PGE1 at a dose of 0.2
      mg/kg/day for 4 weeks reduced significantly the RV/LV + S ratio from 0.428 +/-
      0.070 to 0.243 +/- 0.059 (p < 0.01) and decreased the production of these
      cytokines: IL-1, from 4.675 +/- 3.558 to 1.800 +/- 0.722 units; IL-6, from 0.322
      +/- 0.121 to 0.060 +/- 0.039 units; and TNF, from 0.578 +/- 0.369 to 0.004 +/-
      0.004 units. In another series of experiments, a significant reduction of the
      RV/LV + S ratio was noted for only 1 week when we administered PGE1 immediately
      after the injection of MCT. We confirmed that histopathologic improvements of
      lungs were noted by administering 0. 2 mg/kg PGE1 for 4 weeks. In another
      experiment, PGE1 at a concentration of 2 microg/ml suppressed a rise in the
      cytosolic Ca2+ concentration of lipopolysaccharide-stimulated peritoneal
      macrophages of rats in vitro, suggesting that PGE1 suppressed cytokine production
      by macrophages through the suppression of the Ca2+ influx. These results suggest
      that administering PGE1 may be effective in the treatment of some forms of
      pulmonary hypertension in humans.

PMID- 9929406
TI  - A murine model of latex allergy-induced airway hyperreactivity.
AB  - Sensitization to latex proteins can cause immediate IgE mast cell-mediated
      reactions. Health care workers have been found to be particularly at risk because
      of high exposure. Latex allergy can be produced in mice as demonstrated by IgE
      and eosinophil responses. Thus the mouse is a potential animal model for studying
      this disease, but the airway response to latex sensitization in mice has not been
      evaluated previously. In the present study, we immunized BALB/c mice intranasally
      with nonammoniated latex proteins. Animals were anesthetized, and lung mechanics
      were evaluated plethysmographically. Changes in pulmonary conductance (GL) and
      compliance (Cdyn) were measured in response to a nonspecific challenge with
      methacholine or to a direct challenge with intravenous latex antigen. Latex
      sensitization resulted in elevated levels of IgE and latex-specific IgG1 as well
      as interstitial infiltrates consistent with an allergic response. The
      methacholine dose-response ED50 for GL was 116.4 microg for the control mice and
      fell significantly to 20.9 microg for latex-sensitized mice. The ED50 calculated
      for Cdyn was also significantly lower after latex sensitization. The GL in latex
      sensitized mice challenged with latex antigen fell significantly from a
      prechallenge value of 1.87 +/- 0.41 (S.E.) to 0. 198 +/- 0.03 ml x s-1 x cmH2O
      after latex antigen challenge. The results indicate that latex-sensitized mice
      did exhibit increased airway reactivity in the methacholine challenge test. The
      latex allergic response in mice is unique in that direct challenge with latex
      antigen itself also resulted in a significant airway response.

PMID- 9929407
TI  - Lipid peroxidation of lung surfactant by bacteria.
AB  - The epithelium of the lung is lined with extracellular pulmonary surfactant. This
      is the surface that invading bacteria first come into contact with when they
      enter the alveoli. As bacteria become established and interact with this layer,
      various characteristics of surfactant may become altered. We studied free radical
      production by three bacterial species, group B streptococci, Escherichia coli,
      and Pseudomonas aeruginosa, as well as the effect of two concentrations of lung
      surfactant (Curosurf at 0.04 and 0.4 mg/ml) on this production estimated by the
      nitro blue tetrazolium reduction test. We also measured the lipid peroxidation of
      surfactant at various incubation times (0-20 h), using a LPO-586 test kit. In
      addition, the effect of vitamin E as an antioxidant in a concentration of 0.5
      microM was determined by the lipid peroxidation test. We found that the nitro
      blue tetrazolium reduction by the three bacterial species and lipid peroxidation
      of lung surfactant increased with time. Vitamin E reduced the lipid peroxidation
      of this surfactant. By measuring bacterial growth at various incubation times we
      showed that lung surfactant was bactericidal to group B streptococcal and E. coli
      strains and that P. aeruginosa strains were resistant to surfactant. We conclude
      that bacteria, probably by their production of reactive oxygen species, cause
      lipid peroxidation of lung surfactant.

PMID- 9929409
TI  - 1998 referees 

PMID- 9929408
TI  - Dose dependence and time course of smoke inhalation injury in a rabbit model.
AB  - The dose dependence and time course of smoke inhalation injury were determined in
      a rabbit model. Animals were insufflated with 18-90 breaths of cotton smoke or
      room air (control) at a rate of 18 breaths/min and tidal volume of 12 ml/kg.
      Smoke-exposed animals exhibited dose-related histologic effects with progressive
      deterioration of respiratory function during the postexposure period of
      observation (96 h). The smoke-exposed rabbits had reproducible injuries to both
      airway mucosa and lung parenchyma, manifested by disruption and sloughing of
      airway and alveolar epithelia, and exudation of protein-rich fluid and leukocytes
      into the airway and alveolar spaces. Significant effects were evident by 24 h
      postexposure. Smoke inhalation also affected the respiratory burst of alveolar
      macrophages. Generation of superoxide anions by alveolar macrophages at 48 h
      postexposure was increased significantly after smoke inhalation (54 breaths). The
      present rabbit model should be useful for studying the interactions between
      pulmonary epithelial cells and leukocytes after smoke inhalation and for
      determining the role that abnormal functioning of alveolar macrophages plays in
      the development of smoke inhalation injury.

PMID- 9929410
TI  - Dielectric Spectroscopic and Molecular Simulation Evidence for Aggregation of
      Surfactant-stabilized Calcium Carbonate Nanocolloids in Organic Media.
AB  - Dielectric spectroscopy carried out on overbased phenate micelle particles of
      nominal diameter approximately 2 nm containing calcium carbonate cores in
      hydrophobic liquids indicates that the micelles are strongly aggregated. Mean
      cluster sizes in excess of approximately 10(3) individual micelles are typically
      found in toluene. The level of association is a little higher in dodecane which
      is chemically closer to engine oil, the usual solvent for these systems. The mean
      aggregate size increases dramatically with concentration above an effective
      solids volume fraction of approximately 0.1 on treating the micelles as spheres.
      Aggregate size also depends on the level of overbasing, with lower levels of
      overbasing giving more micelles in the cluster. Molecular dynamics simulations of
      individual micelle particles reveal them to have large dipole moments originating
      mainly from the amorphous carbonate cores. Dipoles of magnitude approximately 20D
      are typical for a range of different surfactant types used in the model. The
      magnitude of the dipole depends somewhat on the chemical composition of the
      stabilizing surfactant shell. Monte Carlo simulations of two phenate nanocolloids
      taking into account all atom and charge pair interactions show these particles to
      have a strong short-range coulombic attraction of typically -25kBT at T = 298 K
      in the favored "side-by-side" relative arrangement. This attraction could be
      responsible for the strong level of association inferred from the dielectric
      spectroscopy experiments. Copyright 1999 Academic Press.

PMID- 9929411
TI  - Studies on the Electrochemical Characterization of Cellulose Acetate and Dowex-50
      Membranes for Uni-Univalent Electrolytes in Aqueous Solutions.
AB  - Membrane potential and bi-ionic potential studies using cellulose acetate and
      Dowex-50 membranes and sodium chloride and potassium chloride aqueous solutions
      have been carried out. The results have been used to estimate solute
      permeability, ionic transport numbers, fixed charge density, and surface charge
      density of both the membranes. Both membrane potential and bi-ionic potential are
      affected by adsorption of ions. Adsorbed ions affect the surface potential as
      well as solute retention capacity of the membranes. Solute retention expressed in
      terms of the "maximal retention" of membranes could thus be estimated.
      Furthermore, a correlation between permselectivity of the membrane and effective
      concentration with the dielectric constant of the membrane has also been
      established. Copyright 1999 Academic Press.

PMID- 9929412
TI  - The Effect of Anomeric Head Groups, Surfactant Hydrophilicity, and Electrolytes
      on n-Alkyl Monoglucoside Microemulsions.
AB  - The effects of the variables of head group structure and salt concentration on
      microemulsions formed in mixtures of water, alkyl ethylene glycol ethers
      (CkOC2OCk), and n-alkyl beta-d-glucopyranosides (CmbetaG1) are explored. Phase
      behavior of mixtures containing an anomer of the surfactant (n-alkyl alpha-d
      glucopyranoside, CmalphaG1), or surfactants with long head groups (n-alkyl
      maltopyranosides, CmG2), or NaCl or NaClO4 as electrolyte are systematically
      reported as a function of temperature and composition. The substitution of n
      alkyl alpha-d-glucopyranosides for n-alkyl beta-d-glucopyranosides causes
      precipitation under some conditions in all mixtures studied. These solubility
      boundaries begin in the water-surfactant binary mixture at the Krafft boundary,
      then extend to high concentrations of both surfactant and oil. Increasing the
      effective length of the surfactant head group by adding CmG2 to water-CkOC2OCk
      CmbetaG1 mixtures moves the phase behavior dramatically up in temperature when
      even small amounts of CmG2 are used. Adding a lyotropic electrolyte, NaCl, to
      water-CkOC2OCk-CmbetaG1 mixtures moves the phase behavior down in temperature,
      while the hydrotropic electrolyte NaClO4 moves the phase behavior up in
      temperature. Copyright 1999 Academic Press.

PMID- 9929413
TI  - Magnetic Resonance Imaging Study of the Dissolution Kinetics of Octanol in Porous
      Media.
AB  - Magnetic resonance imaging (MRI) is used to visualize the dissolution of
      entrapped ganglia or "blobs" of octanol within the pore space of a randomly
      packed bed of glass ballotini, by a mobile aqueous phase. MRI provides three
      dimensional images, able to distinguish the solid, hydrocarbon, and aqueous
      phases, as well as velocity maps of the mobile aqueous phase. Dissolution of the
      hydrocarbon phase has been modeled using a one dimensional advection-dispersion
      description incorporating a mass transfer term between the hydrocarbon and
      aqueous phases. Essential to this mass transfer term is a description of the
      interfacial area between the hydrocarbon and aqueous phases which is actively
      involved in dissolution and which can be determined directly from the images. The
      experimental data are best modeled by evaluating an effective interfacial area
      term characterizing the hydrocarbon/water boundary which excludes the narrowest
      constrictions within the interparticle space. MRI visualizations of the structure
      of the pore space and the flow processes occurring within it, demonstrate that
      heterogeneities in the flow at the length-scale of individual pores within the
      interparticle space cause significant heterogeneity in the dissolution process
      which becomes significant at low hydrocarbon saturations. Copyright 1999 Academic
      Press.

PMID- 9929414
TI  - Adsorption of NOM onto Activated Carbon: Effect of Surface Charge, Ionic
      Strength, and Pore Volume Distribution.
AB  - Adsorption of natural organic matter (NOM) onto seven activated carbons with a
      wide range of surface properties was studied at high and low ionic strength over
      a range of pH values. From adsorption isotherm studies it was found that, for six
      of seven carbons, at low surface concentrations, increased ionic strength
      decreased NOM adsorption. As the surface concentration increased, the adsorption
      isotherms converged and intersected, after which the addition of salt resulted in
      increased adsorption. This "crossover point" marked a change in the adsorption
      mechanism from the "screening reduced" to the "screening enhanced" adsorption
      regimes. The adsorption mechanisms are extremely complicated and appear
      attributable to various factors, including electrostatic forces, pore volume
      distribution, and chemical interactions between the NOM and the surface
      functionalities on the carbon surfaces. Copyright 1999 Academic Press.

PMID- 9929415
TI  - Encapsulation of Inorganic Particles by Dispersion Polymerization in Polar Media.
AB  - Following a previous work (Bourgeat-Lami, E., and Lang, J., J. Colloid Interface
      Sci. 197, 293 (1998)), encapsulation of silica beads has been achieved by
      dispersion polymerization of styrene in an aqueous ethanol medium using poly(N
      vinyl pyrrolidone) as stabilizer. Silica beads, prepared according to the Stober
      method, were coated prior to polymerization by grafting 3-(trimethoxysilyl)propyl
      methacrylate onto the surface. A great number of silica beads per composite
      particle were previously found using beads that had diameters between 49 and 120
      nm. In the present work, larger silica beads with diameters between 191 and 629
      nm are investigated. We demonstrate by transmission electron microscopy that,
      consequently, only a small number of silica beads are contained in the composite
      particles. By counting the composite particles containing precisely zero, one,
      two, three, four, and more than four silica beads, it clearly appears that the
      encapsulation of only one silica bead can be obtained simply by increasing the
      size of the beads. Under our experimental conditions, the optimal bead diameter
      for achieving composite particles containing only one silica bead turns out to be
      around 450 nm. We show that increasing the silica bead size above this value
      results in an increased number of composite particles without silica beads. In
      contrast, the number of composite particles with two, three, four, or more than
      four silica beads increases with decreasing silica bead size. In addition to the
      above variations in composition of the composite particles, changes in particle
      shapes were also observed as a function of the size of the silica beads and the
      styrene concentration in the polymerization medium. Hypotheses concerning these
      variations are presented. Copyright 1999 Academic Press.

PMID- 9929416
TI  - Recognition of Amphiphiles with Many Pendent Galactose Residues by Ricinus
      communis Agglutinin.
AB  - Amphiphiles which carry many pendent galactose residues as side chains were
      prepared by telomerization of 2-methacryloyloxyethyl beta-D-galactopyranoside
      (MEGal) or 3-(2-methacryloyl aminoethylthio)propyl D-galactopyranoside (MEPGal,
      alpha:beta = 3.9:1) using a lipophilic radical initiator. The galactose-carrying
      amphiphiles (DP (degree of polymerization) = 15) incorporated in liposomes were
      recognized by a lectin from Ricinus communis (RCA120), which was proven by the
      increase in turbidity of the liposome suspension after mixing with the lectin.
      The recognition was largely affected by the distance between the galactose
      residues and the polymer main chain, and the surface density of the amphiphile in
      the liposomes. The liposomes containing these galactolipids were not taken up by
      mouse peritoneal macrophages, probably due to a steric hindrance of polymer main
      chains from the uptake of D-galactose receptors on the macrophages. Copyright
      1999 Academic Press.

PMID- 9929417
TI  - Motion of a Colloidal Sphere Covered by a Layer of Adsorbed Polymers Normal to a
      Plane Surface.
AB  - A combined analytical-numerical study is presented for the slow motion of a
      spherical particle coated with a layer of adsorbed polymers perpendicular to an
      infinite plane, which can be either a solid wall or a free surface. The Reynolds
      number is assumed to be vanishingly small, and the thickness of the surface
      polymer layer is assumed to be much smaller than the particle radius and the
      spacing between the particle and the plane boundary. A method of matched
      asymptotic expansions in a small parameter lambda incorporated with a boundary
      collocation technique is used to solve the creeping flow equations inside and
      outside the adsorbed polymer layer, where lambda is the ratio of the
      characteristic thickness of the polymer layer to the particle radius. The results
      for the hydrodynamic force exerted on the particle in a resistance problem and
      for the particle velocity in a mobility problem are expressed in terms of the
      effective hydrodynamic thickness (L) of the polymer layer, which is accurate to
      O(lambda2). The O(lambda) term for L normalized by its value in the absence of
      the plane boundary is found to be independent of the polymer segment distribution
      and the volume fraction of the segments. The O(lambda2) term for L, however, is a
      sensitive function of the polymer segment distribution and the volume fraction of
      the segments. In general, the boundary effects on the motion of a polymer-coated
      particle can be quite significant. Copyright 1999 Academic Press.

PMID- 9929418
TI  - A Thermodynamic Model for Gas Adsorption Isotherms.
AB  - In this paper based on the principle of solution thermodynamics for gas-solid
      equilibrium, a relation is developed to express gas adsorption isotherms. An
      activity coefficient model based on weight fraction of sorbate in the solid phase
      has been derived that well describes the behavior of various gases on different
      types of adsorbents. The proposed model has been evaluated and compared with four
      other models commonly used for gas adsorption isotherms in the literature. For 12
      different systems at various isotherms for the temperature range -128 to 100
      degreesC and the pressure range 0.02 to 1219 kPa for 689 data points, the
      proposed model predicts equilibrium pressure with an average deviation of 5.3%,
      which is about half of the error obtained from other methods. The proposed model
      clearly outperforms other available methods such as the vacancy solution theory,
      the ideal adsorption solution model, and other various modified forms of the
      Langmuir isotherm. Unique features of the proposed model are its simplicity,
      generality, and accuracy over the entire pressure and temperature ranges.
      Copyright 1999 Academic Press.

PMID- 9929419
TI  - A Molecular Theory of the Hydration Force in an Electrolyte Solution.
AB  - A model, consisting of a pair of large macroions in a dipolar hard sphere-point
      ion electrolyte, is considered in order to evaluate the hydration force (solvent
      mediated) contribution to the force between colloidal particles, which is missing
      in the DLVO theory. Using the mean spherical approximation (MSA), an explicit
      expression for this force is obtained. It is shown that the force consists of the
      hard-core exclusion term that was proposed recently by Henderson and Lozada
      Cassou (HLC) [J. Colloid Interface Sci. 121, 486 (1988)], and a dipole alignment
      contribution that originates from the orientational ordering of the solvent
      molecules near the colloidal particles. The long-range asymptotic form of the
      total force is given by a Coulomb contribution and is described by the Poisson
      Boltzmann or Derjaguin-Landau-Verwey-Overbeek (DLVO) result. The hydration force
      is short-ranged and extends about ten solvent layers and is responsible for the
      oscillations of the total force. The total force that we obtain is similar to the
      semiempirical result of HLC. The comparison with the experimental results for a
      10(-3) M KCl electrolyte solution is discussed. Copyright 1999 Academic Press.

PMID- 9929420
TI  - The Equilibrium Properties and Microstructure of Mixtures of Colloidal Particles
      with Long-Range, Soft Repulsions.
AB  - Osmotic pressure and elastic moduli of bimodal suspensions of particles
      experiencing long-range, soft repulsions were measured. At fixed osmotic
      pressure, the total suspension volume fraction, &phi;, varies linearly as the
      mixing ratio &phi;l/&phi; is increased from 0 to 1. Here &phi;l is the volume
      fraction of large particles based on total suspension volume. This result
      suggests the suspensions studied here are phase separated into domains containing
      primarily small and primarily large particles and is not expected for hard sphere
      suspensions where, at fixed osmotic pressure, &phi; passes through a maximum as
      &phi;l/&phi; is increased. Elastic moduli are well described by a model based on
      a composite microstructure where the domains of pure large and small particles
      must have the same osmotic pressure which fixes the local particle volume
      fraction and hence the elastic modulus in each phase. The existence of phase
      separation is supported by electron micrographs taken on samples prepared by
      rapidly drying suspensions with volume fractions near 0.6. Copyright 1999
      Academic Press.

PMID- 9929421
TI  - The Rheology of Bimodal Mixtures of Colloidal Particles with Long-Range, Soft
      Repulsions.
AB  - The rheological properties of dense suspensions of bimodal mixtures of colloidal
      particles with long-range, soft repulsions were investigated. Suspensions of
      particles suspended in 10(-4) M KCl with volume fractions ranging from 0.3-0.6
      were studied for volume fraction ratios of large to small particles of 0, 0.25,
      0.5, 0.75, and 1.0. Latex particles of diameters ranging between 105 to 544 nm
      were used. These particles were stabilized by a combination of electrostatic and
      short range steric repulsions. Four separate mixtures were investigated with size
      ratios (large/small) of 1.2-5. At volume fractions investigated, the suspensions
      displayed dynamic yield stresses, tauy, and shear thinned with increasing stress
      or shear rate. The yield stress was found to be proportional to the suspension's
      elastic modulus, with a constant of proportionality lying between 0.015 and 0.03
      as has been reported for a wide range of monodisperse suspensions. The functional
      dependence of stress on shear rate could be reduced to a single master curve
      which was independent of volume fraction, particle size ratio, and mixing ratio
      by scaling tauy on G, and the shear rate on G/etac where etac is the continuous
      phase viscosity. In bimodal suspensions shear thickening accompanied by
      irreversible aggregation was observed at volume fractions substantially below
      that measured for monodisperse suspensions. The stress and shear rate at
      thickening decreased rapidly as the volume fraction of the mixed suspension was
      increased. These results are substantially different than what has been reported
      for well-mixed suspensions of particles experiencing "hard" repulsions in that as
      the fraction of large particles is increased no viscosity minimum is seen at low
      and intermediate shear rates. Copyright 1999 Academic Press.

PMID- 9929422
TI  - Development of Composite Adsorbents of Carbon and Intercalated Clay for N2 and O2
      Adsorption: A Preliminary Study.
AB  - Composite adsorbents of carbon and alumina intercalated montmorillonite were
      prepared and characterized by adsorption of N2 and O2 at various temperatures.
      The effects of pyrolysis, temperature, heating rate, subsequent degassing, and
      doping of cations and anions were investigated. The adsorption capacities of the
      composite adsorbents developed at higher temperatures (0 and -79 degreesC) are
      found to be larger than those of normal alumina pillared clays. The experimental
      results showed that the framework of these adsorbents is made of alumina
      particles and clay sheets while the pyrolyzed carbon distributes in the space of
      interlayers and interpillars. The pores between the carbon particles, clay
      sheets, and alumina pillars are very narrow with very strong adsorption forces,
      leading to enhanced adsorption capacities at 0 and -79 degreesC. The composite
      adsorbents exhibit features similar to those of carbonaceous adsorbents. Their
      pore structures, adsorption capacities, and selectivities to oxygen can be
      tailored by a controlled degassing procedure. Meanwhile, ions can be doped into
      the adsorbents to modify their adsorption properties, as usually observed for
      oxide adsorbents like zeolite and pillared clays. Such flexibility in pore
      structure tailoring is a potential advantage of the composite adsorbents
      developed for their adsorption and separation applications. Copyright 1999
      Academic Press.

PMID- 9929423
TI  - Modification of Surface Charge Properties during Kaolinite to Halloysite-7A
      Transformation.
AB  - The surface charge properties of well and poorly ordered kaolinite and halloysite
      7A, representing three different stages of kaolinite to halloysite-7A
      transformation identified in the kaolin deposit of Sao Vicente de Pereira
      (Portugal), were studied. Mineralogical (X-ray diffraction, Fourier
      transformation-infrared) and chemical data (analytic electron microscopy) showed
      that the gradual transformation from kaolinite to halloysite-7A minerals was
      accompanied by an increase in hydration and a decrease in Si/Al ratio. In
      particular, the replacement of Si(IV) by Al(III) in the tetrahedral layer caused
      an electrical charge unbalance and a modification of surface charge properties
      during the kaolinite to halloysite transformation. Accordingly, the cation
      exchange capacity (CEC) gradually increases when passing from well-ordered
      kaolinite to halloysite-7A, attesting the direct correspondence existing among
      the structural order of the samples, number of tetrahedral substitutions, and
      CEC. Electrophoretic experiments provided further evidences of the origin of
      surface charge properties and the variation encountered during kaolinite to
      halloysite-7A transformation. The curves of zeta-potential versus pH show the
      same pH dependency for the three minerals, but a gradual increase of zeta
      potential when passing from well ordered kaolinite to halloysite-7A through the
      poorly ordered kaolinite. The results can unambiguously be attributed to the
      increase of permanent charge due to the higher degree of isomorphic substitution,
      more than to the increase of structural and ionizable water. Copyright 1999
      Academic Press.

PMID- 9929424
TI  - Study of Water Adsorption on Activated Carbons with Different Degrees of Surface
      Oxidation.
AB  - A carbon of wood origin was oxidized with different oxidizing agents (nitric
      acid, hydrogen peroxide, and ammonium persulfate). The microstructural properties
      of the starting material and the oxidized samples were characterized using
      sorption of nitrogen. The surface acidity was determined using Boehm titration
      and potentiometric titration. The changes in the surface chemistry were also
      studied by diffuse reflectance FTIR. Water adsorption isotherms were measured at
      three different temperatures close to ambient (relative pressure from 0.001 to
      0.3). From the isotherms the heats of adsorption were calculated using a virial
      equation. The results indicated that the isosteric heats of water adsorption are
      affected by the surface heterogeneity only at low surface coverage. In all cases
      the limiting heat of adsorption was equal to the heat of water condensation (45
      kJ/mol). Copyright 1999 Academic Press.

PMID- 9929425
TI  - Rotating Ring (Pt)-Disc (FeS2) Electrode Behavior in Hydrochloric Solutions.
AB  - A rotating ring (Pt)-disc (FeS2) electrode was used to investigate the surface
      oxidation process of pyrite in the hydrochloric solutions. It is reported for the
      first time that the oxidation intermediates of pyrite were formed on the disc
      electrode and then oxidized on the ring electrode. The results indicate that at a
      rotation rate of 20 Hz, when the disc electrode potential was in the region of
      0.43 to 0.62 V and the ring electrode potential was at 1 V vs a standard calomel
      electrode (SCE), approximately 50% of the reacted pyrite was oxidized to ferric
      and sulfate ions and the other 50% was oxidized to sulfur and ferrous ions on the
      disc electrode. The latter was further oxidized to ferric ions on the ring
      electrode. As the disc electrode potential increased to 1.22 V vs SCE, more than
      90% of the reacted pyrite was oxidized to ferric and sulfate ions on the disc
      electrode and less than 10% formed ferrous ions, which were further oxidized to
      ferric ions on the ring electrode. Copyright 1999 Academic Press.

PMID- 9929426
TI  - Parameter Estimation for the Constant Capacitance Surface Complexation Model:
      Analysis of Parameter Interdependencies.
AB  - Results of extensive application of the 2-pK constant capacitance surface
      complexation model (CCM) to surface charge data of a range of minerals in 0.1 M
      electrolytes are summarized where the program FITEQL has simultaneously been used
      to study the interdependence of the involved optimized parameters. To illustrate
      representative results, surface complexation and goodness of fit parameters are
      given as a function of the capacitance value (C). For all (ca. 150) tested data
      sets, one of three patterns is observed, two of which do not allow a unique
      parameter set to be obtained. The results indicate that the optimized site
      density parameter is relatively insensitive to a wide variation of C; optimized
      site density is rather low in this range of (higher) C and tends toward maximum
      proton uptake in the respective data set which in turn will be close to sometimes
      experimentally observed saturation levels. At low and with further decreasing C a
      steep increase of site density may occur; in this case, DeltapKa strongly
      increases after a DeltapKa minimum. Alternatively at low C, DeltapKa may continue
      to decrease and site density decreases simultaneously after a site density
      maximum. The observed patterns can be explained by the constraint of C on the
      electrostatic correction factor. Linear correlation coefficients (which are very
      useful parameters but do not receive much attention) show that in the region of
      low C, the optimized parameters become fully correlated, which finally causes
      nonconvergence in parameter optimization. In the region where the optimized site
      density is not significantly affected by a decrease in C the optimized parameters
      are more weakly correlated. When site concentration is co-optimized high
      correlation between adjustable parameters suggests that it is preferable to have
      an estimate for this parameter. Overall, it can be stated that substantial
      difficulties were observed in the effort to obtain unique (and thus meaningful)
      parameters for the CCM in about 60% of the data sets treated. Copyright 1999
      Academic Press.

PMID- 9929427
TI  - Adhesion Probability of Colloidal Particles with Repulsive Soft Interaction.
AB  - Computer simulations of the irreversible adhesion of charged colloidal particles
      at a solid/liquid interface are performed to determine whether the distribution
      of particles in the vicinity of a preadsorbed (also charged) one follows the
      Boltzmann law applied to an a priori uniform adhesion probability, as first
      assumed by Adamczyk et al. (J. Colloid Interface Sci. 140, 123 (1990)). If true,
      this would indicate that the whole information on the deposition process is
      contained in the potential energy distribution on the adsorbing surface. In
      general, diffusion in a field of force and the irreversibility of the process
      induce significant deviations from the Boltzmann-weighted uniform adhesion
      density. Nevertheless, it is shown that for particles characterized by a small
      gravitational energy this procedure leads to a reasonable first approximation of
      the distribution of the particles over the adsorbing surface. This observation
      thus demonstrates the validity of Adamczyk's assumption and extends its range of
      applicability to the case of a weak gravitational field. Copyright 1999 Academic
      Press.

PMID- 9929428
TI  - Electroosmotic Velocity in Fibrous Porous Media.
AB  - A theory of electroosmosis in an array of parallel cylindrical fibers of Kozak
      and Davis (J. Colloid Interface Sci., 112, 403 (1986)), in which the liquid flow
      is normal to the axes of the cylinders, is developed to derive a simple
      approximate expression for the electroosmotic velocity for low zeta potentials
      without involving numerical integration. The relative error is less than 6%.
      Copyright 1999 Academic Press.

PMID- 9929429
TI  - Hydrophobic Forces in Thin Water Films Stabilized by Dodecylammonium Chloride.
AB  - A thin film balance of Scheludko-Exerowa type was used to determine equilibrium
      film thicknesses of dodecylammonium chloride (RNH3Cl) solutions. The data were
      analyzed in view of the extended DLVO theory, which considers electrostatic, van
      der Waals, and hydrophobic forces. The hydrophobic force was represented as a
      power law which is of the same form as for the van der Waals force, so that its
      constant K232 can be directly compared with the Hamaker constant, A232. The
      results showed that at low surfactant concentrations, K232 is positive and
      decreases with increasing surfactant concentration, suggesting that hydrophobic
      force plays an important role in thin films. When the K232 versus concentration
      plot was extrapolated to very dilute solutions, K232 approaches 10(-17) J, which
      is approximately 270 times larger than A232. When the surfactant concentration
      was increased above 2 x 10(-3) M, however, K232 becomes negative, indicating that
      hydration force appears at high surfactant concentrations. These results suggest
      that air bubbles are hydrophobic and the hydrophobicity decreases with increasing
      surfactant concentration. A TFB was used to obtain a disjoining pressure isotherm
      at 10(-3) M RNH3Cl in the presence of 10(-4) M NaCl. The results can be fitted to
      the extended DLVO theory with K232 = 6 x 10(-19) J. Consideration of hydrophobic
      force predicted a rupture thickness larger than predicted using the DLVO theory,
      but is substantially smaller than the experimental result. This discrepancy may
      be ascribed to the hydrodynamic force operating in the film thinning process.
      Copyright 1999 Academic Press.

PMID- 9929430
TI  - Copper Phthalocyanine-Mica Interactions in Nonaqueous Media.
AB  - The interaction forces and adhesion of copper phthalocyanine particles with a
      mica substrate in isoparaffin were directly measured using an atomic force
      microscope. The study was conducted primarily to investigate the stabilization
      mechanism of copper phthalocyanine dispersions in a nonaqueous medium. The nature
      of the forces was examined in the presence of various concentrations of water and
      zirconium octanoate, both of which are present at the particle-isoparaffin
      interface. A weak attraction, as well as a small adhesion, exists between the
      copper phthalocyanine particles and the mica surface. These interactions are a
      function of the water content of the hydrocarbon phase and appear to be a result
      of capillary forces. The addition of zirconium octanoate produces significant
      short range repulsive forces with no adhesion between the copper phthalocyanine
      and mica surfaces. The shape of the force against distance curves suggests that
      the dispersion stability of the copper phthalocyanine arises through steric
      stabilization by adsorbed zirconium octanoate. The same qualitative interaction
      behavior was observed when the copper phthalocyanine particle was coated with a
      layer of polyvinyl acetate latex. Copyright 1999 Academic Press.

PMID- 9929431
TI  - Surface Modification of Conventional Polymers by Depositing Plasma Polymers of
      Trimethylsilane and of Trimethylsilane + O2.
AB  - The static wetting properties of TMS (trimethylsilane) and TMS + O2 plasma
      deposited films on eleven low energy conventional polymers were investigated
      using the sessile droplet method. The static advancing contact angle is an
      excellent indication of the change in surface state properties from plasma
      surface modification. However, traditional contact angle measuring techniques
      possess a methodological limitation, which can leave a water droplet on the
      substrate surface for up to 3 min before a measurement is obtained. The static
      "advancing" contact angles of different size water droplets on teflon and nylon
      surfaces were observed to change significantly in 2 min while equilibrating with
      the surface and surroundings. A new quick image-capturing device enables static
      contact angle measurement 2 to 4 s after contact with the substrate. This
      technique virtually eliminates the time dependent effects of evaporation and
      surface state change, which are believed to be responsible for the change in
      static advancing contact angles. Furthermore, static contact angles independent
      of droplet volume and contact time may be taken as a surface characteristic
      property, which is denoted as the intrinsic static contact angle, &theta;S. The
      static "advancing" contact angle, measured in this fashion, indicated that the
      wetting properties of TMS and TMS + O2 plasma polymer deposition on 10
      conventional polymers were modified virtually independent of the underlying
      substrate. The average advancing contact angles on TMS and TMS + O2 modified
      polymers are &theta;S = 94 +/- 2.2 (cos &theta;S = -0.0645) and &theta;S = 32 +/-
      6.9 (cos &theta;S = 0.8452), respectively. Copyright 1999 Academic Press.

PMID- 9929432
TI  - Surface Modification of Conventional Polymers by Depositing Plasma Polymers of
      Trimethylsilane and of Trimethylsilane + O2.
AB  - The dynamic wetting properties of TMS (trimethylsilane) and TMS + O2 plasma
      deposited films on ten low energy conventional polymers were investigated using
      the Wilhelmy balance method. Plasma deposition resulted in wetting properties
      that were independent of the underlying polymer substrate for the majority of
      polymers studied. TMS plasma modification resulted in virtually the same degree
      of hydrophobicity with an average cosine of the dynamic advancing contact angle
      from the first immersion, cos &theta;D,a,1 = -0.381 (&theta;D,a,1 = 112 +/- 3.6),
      for eight of the ten polymers. PTFE and UHMWPE were slightly more hydrophobic
      after TMS plasma treatment with an average cos &theta;D,a,1 = -0.785
      (&theta;D,a,1 = 141 +/- 4.2). TMS + O2 plasma modification resulted in high
      wettability of all polymers with an average cos &theta;D,a,1 = 0.654
      (&theta;D,a,1 = 49.2 +/- 11.7). Dynamic hysteresis, mainly a result of the change
      in meniscus shape during immersion and emersion, and intrinsic hysteresis, due to
      the extent of surface configuration change, were both found to vary according to
      the size of the polymer plate. In general, dynamic hysteresis can be quite large
      for more hydrophobic TMS treated polymers and considerably smaller for highly
      hydrophilic TMS + O2 treated polymers. The extent of intrinsic hysteresis of only
      TMS treated polymers was found to be independent of the underlying polymers
      within the time-scale of wetting. TMS + O2 plasma treatment resulted in wide
      variations in intrinsic hysteresis probably due to substrate specific etching of
      oxygen plasma species. The wettability of the untreated and TMS and TMS + O2
      treated polymers, indicated by the static "advancing" contact angles from the
      sessile droplet method and dynamic "advancing" and "receding" contact angles from
      the Wilhelmy balance method, were found to conform well to the correlation, cos
      &theta;S = (cos &theta;D,a,1 + cos &theta;D,r,1)/2. Copyright 1999 Academic
      Press.

PMID- 9929433
TI  - Mercury Intrusion Porosimetry and Image Analysis of Cement-Based Materials.
AB  - Mercury intrusion porosimetry (MIP) is a widely used technique for characterizing
      the distribution of pore sizes in cement-based materials. It is a simple and
      quick indirect technique, but it has limitations when applied to materials that
      have irregular pore geometry. The relationship between MIP results and the actual
      pore distribution and connectivity can be better understood with the use of image
      analysis. This paper discusses the use of MIP to describe the pore structure of
      cements and the efforts to validate the technique with microscopy. In particular,
      a study using molten Wood's metal as an alternate intrusion liquid that is solid
      in the pores at room temperature and can be examined by scanning electron
      microscopy will be presented. Results of the image analysis and the intrusion
      behavior of Portland cement mortars will be discussed. Copyright 1999 Academic
      Press.

PMID- 9929434
TI  - Surface Complexation of Calcite by Carboxylates in Water.
AB  - Small molecules that have two carboxylic functions can adsorb from water onto
      calcite. The adsorption site is a -Ca+ site. The mechanism of adsorption is a
      complexation of the -Ca+ site by the two carboxylates, similar to the solution
      complexation of Ca++ ions. The complex has a ring structure where the two
      carboxylates are joined on one side by the -Ca+ ion and on the other by the n CH2
      groups of the small molecule. Five-bond rings (n = 0) are the most stable,
      followed by six-bond rings (n = 1) and seven-bond rings (n = 2). Five-bond rings
      can also be formed with one carboxylate and one hydroxyl group (this is the case
      for alpha-hydroxycarboxylates) or with one enolate and one hydroxyl group
      (catechol). The sequence of binding strengths is enolate > carboxylate >
      hydroxyl; it matches the sequence of complexation efficiencies of these groups in
      solution and their characters as electron donors toward the metal cation.
      Copyright 1999 Academic Press.

PMID- 9929435
TI  - Surface Complexation Modeling of Yb(III), Ni(II), and Cs(I) Sorption on
      Magnetite.
AB  - The sorption of ytterbium, nickel, and cesium on magnetite is studied via
      experiments. The affinity of the magnetite surface is greater for ytterbium, then
      nickel, and nonexistent for cesium. Three different surface complexation models,
      with three different electrostatic descriptions of the interface, are used to fit
      the experiment data. These descriptions are given by the double layer model
      (DLM), the constant capacitance model (CCM), and a nonelectrostatic model (NEM).
      The results of fits give the same stoichiometries for the surface reactions for
      the three tested models in similar surface loading conditions. The values of the
      surface constants obtained are the same, taking into account the error for DLM
      and CCM. NEM gives different values, even if the fit quality is comparable.
      Copyright 1999 Academic Press.

PMID- 9929436
TI  - Monolayer Adsorption for the Subcritical Lattice Gas and Partially Miscible
      Binary Mixtures.
AB  - Lattice theories have been used extensively to predict and correlate liquid
      liquid equilibria in mixtures. Lattice theories also have been used to predict
      the behavior of gases adsorbing onto solid surfaces. Here, we use a lattice model
      based on the ideas of Ono and Kondo to predict the phase behavior in adsorbed
      monolayers for systems that are below their bulk-phase critical points. For such
      an analysis, it is important that molecular behavior in the bulk and the adsorbed
      layer is based on consistent assumptions. Here, this is accomplished by treating
      the fluid in the bulk as well as in the adsorbed layer as a strictly regular
      solution. Interesting new adsorption isotherms and phase diagrams are generated
      that provide useful insights into adsorption of both lattice gases (i.e.,
      "mixtures" of molecules and holes) and dense lattice liquids (i.e., "mixtures" of
      molecules without holes), illustrating the similarities between adsorption of
      gases and liquids. Copyright 1999 Academic Press.

PMID- 9929437
TI  - The Branching of Reversed Polymer-like Micelles of Lecithin by Sugar-Containing
      Surfactants.
AB  - The effects of n-dodecyl-beta-D-glucopyranoside and n-dodecyl-beta-D
      lactobionamide on the formation and rheological behavior of lecithin organogels
      consisting of reverse long cylindrical (polymer-like) micelles were studied by
      oscillating rheology. The alkylglucoside addition results in a decrease of the
      zero shear viscosity and plateau modulus of the organogel, whereas the
      lactobionamide derivative causes an increase of these parameters. Despite their
      different effects, both the sugar-containing surfactants change the scaling
      exponents of the zero shear viscosity, plateau modulus, and terminal relaxation
      time in a similar way. Before their addition, the scaling behavior is in a
      satisfactory agreement with that expected from a model by Cates who considered
      polymer-like micelles as linear and flexible. In mixtures of lecithin with n
      dodecyl-beta-D-glucopyranoside or n-dodecyl-beta-D-lactobionamide, the power law
      exponents are close to the theoretical predictions that follow from a model for
      branched (connected) cylindrical micelles. It was concluded that both the sugar
      containing surfactants bring about a change in the growing mechanism of the
      lecithin micelles in nonpolar media. A molecular model is considered. This takes
      into account the formation of hydrogen bonds between amphiphile molecules,
      occurrence of packing constraints, and a change of excess free energy of the
      micellar endings. Copyright 1999 Academic Press.

PMID- 9929438
TI  - Onset of Percolation and Fractal Classification Scheme for Multilamellar Lipid
      Vesicles.
AB  - Percolation, like phase transition, expresses a critical property of an assembly.
      The paper provides a brief description of the onset of percolation and the
      fractal behavior of clusters formed as a result of spontaneous assembly of
      multilamellar lipid vesicles (MLVs). The onset of percolation was studied using a
      series of mixed lipid systems. The percolation threshold showed a strong linear
      dependence on the net charge of the constituent lipids. Second, the vesicular
      clusters were characterized using a canonical coordinate frame spanned by the
      fractal dimension and the porosity of the cluster images. MLVs made of different
      lipid constituents formed different domains on such representations. The location
      of the individual domains relative to a simulated random cluster seemed to
      provide a measure of order-element present in such clusters. The specificity of
      the domain locations and their sensitivity to alteration in a microenvironment
      was studied in some detail. Copyright 1999 Academic Press.

PMID- 9929439
TI  - Some Remarks on the Components of the Liquid Surface Free Energy.
AB  - Measurements of the contact angle for water, glycerol, formamide, and ethylene
      glycol on paraffin, polytetrafluoroethylene (PTFE), polyethylene (PE), polyvinyl
      chloride (PVC), polymethyl methacrylate (PMMA), and polyethylene terephthalate,
      for diiodomethane on PE, PVC, PMMA, and PET, and for a series of n-alkanes from n
      heptane to n-hexadecane on PTFE were made. On the basis of the contact angles
      obtained on paraffin, PTFE, and PE the Lifshitz-van der Waals components of the
      glycerol, formamide, and ethylene glycol surface free energy were determined.
      Next, by using the contact angle values of water, glycerol, formamide, ethylene
      glycol, and diiodomethane, the values of the electron-acceptor and electron-donor
      parameters of the acid-base components of the surface free energy of glycerol,
      formamide, and ethylene glycol were calculated and compared with the values taken
      from the literature. It was found that the Lifshitz-van der Waals component of
      the formamide surface free energy and the electron-acceptor and electron-donor
      parameters of the glycerol, formamide, and ethylene glycol surface free energy
      determined in the above-mentioned way differ from those determined by van Oss et
      al. and by Lee. They are closer to those determined on the basis of interfacial
      tension measurements. Using the newly determined components and parameters it was
      found that PVC has an electron-acceptor character in contrast to an electron
      donor character in the literature. Copyright 1999 Academic Press.

PMID- 9929440
TI  - Ultrasonic Study of the L Phase of the CTAB/Benzyl Alcohol/Water System.
AB  - The L phase of the ternary CTAB/benzyl alcohol/water system that extends from the
      water corner to the alcohol corner was studied by the sound velocity method which
      indicated variations in velocity when the aggregate structure changed from normal
      micelles in water to reverse micelles in the alcohol corner of the phase diagram.
      From these results it was concluded that the transition from normal to reverse
      micelles takes place while passing through two different bicontinuous regions,
      one of them with alcohol micro domains dispersed in water and the other one as a
      bicontinuous reverse region with the predominance of the water domains dispersed
      in alcohol. Copyright 1999 Academic Press.

PMID- 9929441
TI  - Low-Temperature Formation of alpha-Alumina by Doping of an Alumina-Sol.
AB  - In our present study, the phase transition behavior of gamma-alumina doped by an
      alumina-sol was explored using X-ray powder diffraction and transmission electron
      microscopy. It was found that the addition of an alumina-sol into gamma-alumina
      enabled the onset of the gamma- to alpha-alumina transformation at temperatures
      as low as 600 degreesC. This phenomenon was designated as the "sol-effect."
      Although the onset temperature of the phase transformation was very low, the
      transformation was completed at 1100 degreesC which is the same as that observed
      with the seeding method. Further investigation revealed that the transformation
      was composed of two steps. One occurs over the temperature region from 600 to 950
      degreesC where a slow increase in the content of alpha-alumina is observed. The
      other is the region from 950 to 1100 degreesC where a rapid increase of alpha
      alumina occurs due to "self-seeding." The "sol-effect" produces powders with very
      fine alpha-alumina particle sizes and little agglomeration. Copyright 1999
      Academic Press.

PMID- 9929442
TI  - Nanometer Deformation Caused by the Laplace Pressure and the Possibility of Its
      Effect on Surface Tension Measurements.
AB  - The deformation of solid surfaces caused by the Laplace pressure is analyzed ad
      its effect on the meniscus force measurement is discussed by comparing it with
      the published experimental results of the meniscus force on a surface force
      apparatus. It is found theoretically that the deformation reaches the order of
      several nanometers and reduces greatly the meniscus force when the meniscus
      curvature radius is small. It is concluded that the deviation of the measured
      meniscus force with the surface force apparatus from equation F = 4pigammaR cos
      &theta; for a nanometer meniscus is due neither to the hydrogen bonding
      interaction (Fisher and Israelachvili, Colloids and Surf. 3, 303 (1981)) nor to
      the short range solid-solid interaction (Christenson, J. Colloid Interface Sci.
      121, 170 (1988)). The main reason lies in the deformation of the solid surface
      due to the Laplace pressure. The nanometer deformation of solid surfaces caused
      by the Laplace pressure is of great importance in measuring the meniscus force.
      Copyright 1999 Academic Press.

PMID- 9929443
TI  - Reproducible Preparation of Silver Sols with Small Particle Size Using
      Borohydride Reduction: For Use as Nuclei for Preparation of Larger Particles.
AB  - Silver colloids are useful as substrates for surface enhanced Raman spectroscopy
      (SERS). The results are, however, seldom quantitative as the distribution of
      particle sizes in silver suspensions can vary from sample to sample and thus the
      SERS spectra can vary in intensity. Monodisperse silver sols are relatively
      difficult to prepare compared with gold or latex colloids as the nucleation
      process is difficult to control. Previous workers have used a system where small
      particles are formed in one process and grown in a second reaction. In this paper
      a simple procedure is outlined by which the small, "seed" particles (starter
      sols) can be prepared; this method is simpler and more reproducible than that
      used in the past. The process by which the sols can be grown is not discussed in
      detail here as it is the subject of a forthcoming publication. Copyright 1999
      Academic Press.

PMID- 9929444
TI  - Interaction of VP3(110-121) Peptide with Hepatocyte and Erythrocyte Membrane
      Models.
AB  - The use of synthetic peptides in the goal of developing a new, inexpensive
      vaccine against hepatitis A virus is one of the encouraging approaches followed
      by many laboratories. These peptides have to be well characterized, being their
      physicochemical properties one of the most relevant points to control. In that
      sense, one can consider the study of the peptide interaction with lipid
      monolayers by means of the Wilhelmy plate method, to gain insight into the
      possible mechanism of action at the membrane level. The peptide chosen
      corresponds to the lineal epitope of hepatitis A virus VP3(110-121). As far as
      the lipids used are concerned, they were selected according to the composition of
      hepatocytes and erythrocytes because these structures seem to play an important
      role in hepatitis proliferation and infection. The peptide was able to
      accommodate into lipid monolayers. Interaction was slightly lower in the
      hepatocyte model than in the erythrocyte model, probably due to the presence of
      cholesterol in the hepatocyte membrane. Copyright 1999 Academic Press.

PMID- 9929445
TI  - Preparation and Characterization of a Kaolinite-1-methyl-2-Pyrrolidone
      Intercalation Compound.
AB  - Well-crystallized kaolinite was initially reacted at 60 degreesC with a water
      dimethyl sulfoxide mixture. After washing and characterization, the resulting
      material (Al2Si2O5(OH)4(DMSO)0,4) was reacted with 1-methyl-2-pyrrolidone (NMP)
      at room temperature. The product was a light yellow powder with a stoichiometry
      that attests to the quantitative substitution of the DMSO by the NMP molecules.
      (Al2Si2O5(OH)4(NMP)0,39+/-0,02) was characterized by X-ray diffractometry,
      thermal analysis (simultaneous TG and DSC), and FTIR. The fact that the NMP
      molecules are located in the interlamellar space of the kaolinite permits a
      notable enhancement of the thermal stability of the complex. While the DMSO
      derived system decomposes at 175 degreesC under air, the NMP complex remains
      stable up to 431 degreesC. Copyright 1999 Academic Press.

PMID- 9929446
TI  - Computer Simulation of the Aggregation and Sintering Restructuring of Fractal
      like Clusters Containing Limited Numbers of Primary Particles.
AB  - A random particle computer simulation (in three dimensions) was conducted to
      investigate the structure and aggregation characteristics of small clusters
      (containing limited numbers of primary particles per cluster). Though an
      individual cluster of small size does not satisfy the power law, it was found
      that these aggregated clusters are fractal-like and comply with the fractal power
      law form in a statistical sense. This statistically averaged fractal dimension
      decreases as the clusters become smaller. A cluster-restructuring model is
      further developed to simulate the topological evolution of dendritic structured
      materials due to sintering at high temperatures. Results indicate that the
      cluster fractal dimension increases as sintering proceeds for small clusters, in
      contrast to results for large clusters wherein the topology is retained and the
      fractal dimension remains constant. A relationship of the fractal dimension
      change with the normalized surface area of dendrites for different-sized clusters
      is established. Copyright 1999 Academic Press.

PMID- 9929447
TI  - Kinetic Analyses of Colloidal Crystallization in a Sinusoidal Electric Field as
      Studied by Reflection Spectroscopy.
AB  - The effect of a sinusoidal electric field on crystal growth rates in the
      colloidal crystallization of silica spheres (110 nm in diameter) in exhaustively
      deionized aqueous suspensions has been studied by reflection spectroscopy. Sphere
      concentration is 0.0016 in volume fraction. Nucleation time is shorter than 1 s.
      The crystal growth rates, v, of the body-centered cubic lattices have been
      determined from the increase in the cube root of the intensity in the sharpened
      reflection peaks. The v value is 20 um/s in the absence of an electric field. v
      decreases from 20 to 8 um/s as the voltage applied increases from 0 to 10 V at 1
      Hz. v decreases from 30 to 15 um/s when frequency increases from 0.01 to 10 Hz at
      E = 6 V, and remains constant irrespective of frequencies higher than 10 Hz up to
      10 kHz. Interestingly, the crystallization of bcc lattices is enhanced at low
      frequencies between 0.01 and 0.5 Hz. The main causes for the retardation of
      crystallization at high frequencies and voltages are (a) the additional
      translational fluctuation of the spheres and the surrounding electrical double
      layers by the electric field, and (b) the partial melting of the crystals by the
      shearing forces in an electric field. The importance of electrostatic intersphere
      repulsion resulting from overlap of the electrical double layers and cooperative
      and synchronized fluctuation of colloidal spheres in crystallization processes is
      strongly supported. Copyright 1999 Academic Press.

PMID- 9929448
TI  - Electrophoretic Mobility of Colloidal Particles in Weak Electrolyte Solutions.
AB  - The analytical theory of the thin double layer concentration polarization in
      suspensions of colloidal particles is generalized to the case of weak electrolyte
      solutions, i.e., when the dissociation-recombination equilibrium and rate
      constants have both finite values. It is shown that under the action of a static
      applied field, regions near the particle appear where there is departure from the
      dissociation-recombination equilibrium. The resulting ion and ion-pair sources
      have a strong bearing on their flows, leading to a change of the electrolyte
      concentration gradients around the particle. This phenomenon also modifies the
      value of the particle electrophoretic mobility, which is dependent on the
      concentration polarization. At constant ionic strength, the theoretical maximum
      of the electrophoretic mobility versus zeta potential curve can substantially
      surpass in weak electrolyte solutions the corresponding value attained in strong
      electrolytes. Copyright 1999 Academic Press.

PMID- 9929449
TI  - Aggregation of Egg-Lecithin Vesicles Induced by Iron(III) Chloride.
AB  - Aggregation behaviors of egg-lecithin vesicles were investigated. The crowded
      vesicle solution exhibited an irregular aggregation style in the presence of
      FeCl3. The process was composed of an induction period (2-5 days) and a
      sedimentation process ( approximately 12 h). The vesicles were stabilized by the
      positively charged species such as [(H2O)4Fe(OH)2 Fe(H2O)4]4+ in the induction
      periods. However, after the stationary state, the vesicles began to coagulate due
      to the transformation of the iron species into the inactive one. The existence of
      such time-lag for the aggregation to occur was mainly induced by the transient
      nature of iron(III) in the aqueous solution. Copyright 1999 Academic Press.

PMID- 9929450
TI  - Distance-Time Measurements in Capillary Penetration: Choice of the Coordinate
      System.
AB  - Washburn's equation is a useful tool for studying the penetration of liquids in
      porous media because it predicts a relationship between the distance penetrated
      by the liquid in the porous media, x, and the time spent in this process, t.
      Despite its extended applicability, some problems in the interpretation of the
      results obtained arise from its use in the linearized form of x2 vs t. In this
      paper a careful mathematical analysis of Washburn's equation shows that most of
      the discordance found from its application comes from inadequate use of
      Washburn's equation. To confirm this assessment, the penetration of different
      liquids in plates used in thin-layer chromatography was investigated. From that
      study it has been proved that the alien behavior appearing when Washburn's
      equation is used in a linearized form disappears when it is used in its
      polynomial expression. Copyright 1999 Academic Press.

PMID- 9929451
TI  - Comments on "Adsorption of Dextrin at Mineral/Water Interface" by G. Bhaskar
      Raju, Allan Holmgren, and Willis Forsling.

PMID- 9929453
TI  - Physiological optics in the hummingbird hawkmoth: a compound eye without
      ommatidia 
AB  - The fast-flying day-active hawkmoth Macroglossum stellatarum (Lepidoptera:
      Sphingidae) has a remarkable refracting superposition eye that departs radically
      from the classical principles of Exnerian superposition optics. Unlike its
      classical counterparts, this superposition eye is highly aspherical and contains
      extensive gradients of resolution and sensitivity. While such features are well
      known in apposition eyes, they were thought to be impossible in superposition
      eyes because of the imaging principle inherent in this design. We provide the
      first account of a superposition eye where these gradients are not only possible,
      but also produce superposition eyes of unsurpassed quality. Using goniometry and
      ophthalmoscopy, we find that superposition images formed in the eye are close to
      the diffraction limit. Moreover, the photoreceptors of the superposition eyes of
      M. stellatarum are organised to form local acute zones, one of which is frontal
      and slightly ventral, and another of which provides improved resolution along the
      equator of the eye. This angular packing of rhabdoms bears no resemblance to the
      angular packing of the overlying corneal facets. In fact, this eye has many more
      rhabdoms than facets, with up to four rhabdoms per facet in the frontal eye, a
      situation which means that M. stellatarum does not possess ommatidia in the
      accepted sense. The size of the facets and the area of the superposition aperture
      are both maximal at the frontal retinal acute zone. By having larger facets, a
      wider aperture and denser rhabdom packing, the frontal acute zone of M.
      stellatarum provides the eye with its sharpest and brightest image and samples
      the image with the densest photoreceptor matrix. It is this eye region that M.
      stellatarum uses to fixate flower entrances during hovering and feeding. This
      radical departure from classical Exnerian principles has resulted in a
      superposition eye which has not only high sensitivity but also outstanding
      spatial resolution.

PMID- 9929452
TI  - Plasmodium gallinaceum ookinetes adhere specifically to the midgut epithelium of
      Aedes aegypti by interaction with a carbohydrate ligand.
AB  - During the course of its development in the mosquito and transmission to a new
      vertebrate host, the malaria parasite must interact with the mosquito midgut and
      invade the gut epithelium. To investigate how the parasite recognizes the midgut
      before invasion, we have developed an in vitro adhesion assay based on combining
      fluorescently labelled ookinetes with isolated midgut epithelia from blood-fed
      mosquitoes. Using this assay, we found that Plasmodium gallinaceum ookinetes
      readily adhered to midguts of Aedes aegypti, mimicking the natural recognition of
      the epithelium by the parasite. This interaction is specific: the ookinetes
      preferentially adhered to the lumen (microvillar) side of the gut epithelium and
      did not bind to other mosquito tissues. Conversely, the binding was not due to a
      non-specific adhesive property of the midguts, because a variety of other cell
      types, including untransformed P. gallinaceum zygotes or macrogametes, did not
      show similar binding to the midguts. High concentrations of glycosylated (fetuin,
      orosomucoid, ovalbumin) or non-glycosylated (bovine serum albumin) proteins,
      added as non-specific competitors, failed to compete with the ookinetes in
      binding assays. We also found that the adhesion of ookinetes to the midgut
      surface is necessary for sporogonic development of the parasite in the mosquito.
      Antibodies and other reagents that blocked adhesion in vitro also reduced oocyst
      formation when these reagents were combined with mature ookinetes and fed to
      mosquitoes. Chemical modification of the midguts with sodium periodate at pH 5.5
      destroyed adhesion, indicating that the ookinete binds to a carbohydrate ligand
      on the surface of the midgut. The ligand is sensitive to periodate concentrations
      of less than 1 mmol l-1, suggesting that it may contain sialic-acid-like sugars.
      Furthermore, free N-acetylneuraminic acid competed with the ookinetes in binding
      aasays, while other monosaccharides had no effect. However, in agreement with the
      current belief that adult insects do not contain sialic acids, we were unable to
      detect any sialic acids in mosquito midguts using the most sensitive HPLC-based
      fluorometric assay currently available. We postulate that a specific carbohydrate
      group is used by the ookinete to recognize the midgut epithelium and to attach to
      its surface. This is the first receptor-ligand interaction demonstrated for the
      ookinete stage of a malaria parasite. Further characterization of the midgut
      ligand and its parasite counterpart may lead to novel strategies of blocking
      oocyst development in the mosquito.

PMID- 9929454
TI  - Ionic exchanges of turtle shell in vitro and their relevance to shell function in
      the anoxic turtle 
AB  - To understand more fully the role of the in vivo turtle shell in buffering lactic
      acid produced during prolonged anoxia, powdered turtle shell was incubated in
      vitro at constant pH (6.0, 6.5, 7.0, 7. 5 or 8.0) in electrolyte solutions
      simulating extracellular fluid. Exchanges of ions and CO2 between the shell and
      solution were evaluated by measuring pre- and post-incubation solution
      concentrations of calcium, magnesium, sodium, potassium, chloride, phosphate and
      lactate. The production of CO2 from the shell and lactate within the shell were
      also measured. We observed that calcium and magnesium, but not phosphate, were
      released from the shell in association with CO2 and that the magnitude of release
      of each increased with solution acidity. The amount of acid titration required to
      maintain constant pH also increased as solution pH fell. The CO2 loss, in mmol,
      was approximately half the acid titration (in mmol), indicating that the evolved
      CO2 derives from carbonate. When the incubating solution contained lactate (50
      mmol l-1), lactate entered the shell and again the amount entering the shell
      increased with solution acidity. Shell samples containing high initial lactate
      levels lost lactate to the solution and at high pH (7.5) acidified the solution
      and required NaOH titration for pH-stat control. These results are consistent
      with observations on anoxic turtles in vivo and confirm the important role of the
      shell as a source of buffer and as a storage site for lactate.

PMID- 9929455
TI  - White muscle strain in the common carp and red to white muscle gearing ratios in
      fish 
AB  - White muscle strains were recorded using sonomicrometry techniques for 70 fast
      starts in the common carp Cyprinus carpio L. High-speed cine images were recorded
      simultaneously for 54 of these starts, and muscle strain was calculated
      independently from the digitized outlines of the fish. Sonomicrometry
      measurements of superficial muscle strain were not significantly different from
      the strain as calculated from the theory of simple bending of a homogeneous
      material: superficial muscle strain thus varied with chordwise distance from the
      spine. However, white muscle strain across a transverse section of the myotome
      shows less variation with chordwise position than would be expected from simple
      bending theory. Muscle strains measured using sonomicrometry thus do not
      necessarily represent the more uniform strain predicted for the whole section of
      the fish. White muscle strain can be accurately predicted from the spine
      curvatures as measured from the cine images if the gearing ratio between the red
      and white muscle fibres is known. A model for calculating the gearing ratio from
      the helical muscle fibre geometry was re-evaluated using current data for the
      kinematics of fast-starting C. carpio. This model predicted a mean gearing ratio
      of 2.8 for these fast-starts. A quicker, alternative approach to estimating
      gearing ratio from the position of the centroid of white fibre area is proposed
      and results in ratios similar to those calculated from the model of helical
      geometry. White muscle strains in fish can thus be estimated from measurements of
      spine curvature and muscle distribution alone.

PMID- 9929456
TI  - Muscle strain histories in swimming milkfish in steady and sprinting gaits 
AB  - Adult milkfish (Chanos chanos) swam in a water-tunnel flume over a wide range of
      speeds. Fish were instrumented with sonomicrometers to measure shortening of red
      and white myotomal muscle. Muscle strain was also calculated from simultaneous
      overhead views of the swimming fish. This allowed us to test the hypothesis that
      the muscle shortens in phase with local body bending. The fish swam at slow
      speeds [U<2.6 fork lengths s-1 (=FL s-1)] where only peripheral red muscle was
      powering body movements, and also at higher speeds (2. 6>U>4.6 FL s-1) where they
      adopted a sprinting gait in which the white muscle is believed to power the body
      movements. For all combinations of speeds and body locations where we had
      simultaneous measurements of muscle strain and body bending (0.5 and 0.7FL), both
      techniques were equivalent predictors of muscle strain histories. Cross
      correlation coefficients for comparisons between these techniques exceeded 0.95
      in all cases and had temporal separations of less than 7 ms on average. Muscle
      strain measured using sonomicrometry within the speed range 0.9-2.6 FL s-1 showed
      that muscle strain did not increase substantially over that speed range, while
      tail-beat frequency increased by 140 %. While using a sprinting gait, muscle
      strains became bimodal, with strains within bursts being approximately double
      those between bursts. Muscle strain calculated from local body bending for a
      range of locations on the body indicated that muscle strain increases rostrally
      to caudally, but only by less than 4 %. These results suggest that swimming
      muscle, which forms a large fraction of the body volume in a fish, undergoes a
      history of strain that is similar to that expected for a homogeneous, continuous
      beam. This has been an implicit assumption for many studies of muscle function in
      many fish, but has not been tested explicitly until now. This result is achieved
      in spite of the presence of complex and inhomogeneous geometry in the folding of
      myotomes, collagenous myosepta and tendon, and the anatomical distinction between
      red and white muscle fibers.

PMID- 9929457
TI  - The development of microcracking and failure in bone depends on the loading mode
      to which it is adapted.
AB  - During locomotion, the anterior cortex of the equine radius is loaded
      predominantly in tension, the posterior predominantly in compression. The
      anterior cortex is relatively strong in tension, the posterior in compression. We
      investigated the pattern of failure of specimens from the two cortices using
      laser scanning confocal microscopy. All specimens were loaded in four-point
      bending to increasingly higher loads. We quantified the amount of diffuse
      microcracking on the tensile side of these specimens by observing the amount of
      light emitted under laser illumination. The amount of light emitted agreed well
      with subjective estimates of the amount of microcracking. Tensile microcracks
      first appeared at a strain of approximately 0.004, and all specimens showed
      considerable growth in microcrack density once the tensile strain had passed
      approximately 0.008. In specimens from the posterior cortex, there was little
      compressive microcracking, and such cracks as were present were small and
      diffuse. These specimens failed on the tensile side first. In specimens from the
      anterior cortex, compression cracks were more numerous, longer and less diffuse,
      and specimens failed initially in compression. The patterns of failure in the
      bone tissues of the two cortices are what would be expected assuming they were
      adapted to the mode of loading to which they are usually subjected.

PMID- 9929458
TI  - The importance of the feeding current for oxygen uptake in the water flea daphnia
      magna 
AB  - In the planktonic crustacean Daphnia magna (Branchiopoda, Cladocera), different
      views exist on the mechanism of respiratory gas exchange, ranging from gill
      breathing to general integumentary respiration. The presumed structures for
      specialized gas exchange are located ventrally within the filter chamber, which
      is continuously perfused with the ambient medium for food gathering. To localize
      respiratory gas exchange in D. magna, we determined the contribution of the
      feeding current to total oxygen transport. Combining microscopy with special
      optical techniques, we used a phosphorescent oxygen-sensitive dye for oxygen
      partial pressure (PO2) measurements and applied fluorescent microspheres for flow
      rate analysis. Appendage beat rate was determined by digital image-processing.
      All experiments were carried out on hypoxia-adapted animals with a body length
      ranging from 2.3 to 2.7 mm at 20 degreesC. External PO2 measurement revealed
      oxygen depletion in the ventral body region but essentially no change at
      posterior, lateral and dorsal positions. The PO2 difference between the inflow
      and outflow of the feeding current was 13.0 mmHg (1.73 kPa). The flow rate of the
      feeding current ranged from 1.2 to 5.2 ml h-1 and showed a close correlation with
      appendage beat rate, which varied from 310.4 to 460.7 beats min-1. Model
      calculations based on the Fick principle suggest that oxygen extraction from the
      feeding current satisfies most of the total of oxygen requirement of D. magna.

PMID- 9929459
TI  - Running, breathing and visceral motion in the domestic rabbit (Oryctolagus
      cuniculus): testing visceral displacement hypotheses.
AB  - The relative motion of the visceral mass may be important to ventilation during
      running. A visceral piston hypothesis predicts that, during galloping, cranial
      motion of the liver during expiration and caudal motion of the liver during
      inspiration may characterize efficient quadrupedal mammalian locomotion. Although
      a theoretical model based on vibration mechanics casts doubt on this prediction,
      only limited direct measurements of visceral mass motion during galloping have
      been reported. In the present study, mechanical interactions between running,
      breathing and liver oscillations in the domestic rabbit are recorded using
      synchronized videographic, cineradiographic and pneumotachographic techniques.
      The analysis focuses on the variation in locomotor-respiratory coupling (LRC) and
      on the relative position of the liver. Results from running rabbits show (1)
      variation in phase angle between the locomotor and respiratory periods that is
      inconsistent with the 1:1 LRC ratio that has been reported for other galloping
      mammals; (2) a tendency towards a 1:1 LRC ratio at higher speeds and stride
      frequencies; and (3) that the relative motion of the liver is caudal during
      expiration and cranial during inspiration, which is inconsistent with the
      visceral piston hypothesis. The data presented here are generally consistent with
      the theoretical vibration mechanics model for liver motion and with a pneumatic
      stabilization hypothesis that the lungs serve an important role in the
      stabilization of the thorax during locomotion.

PMID- 9929460
TI  - Lactate metabolism and glucose turnover in the subterranean crustacean niphargus
      virei during post-hypoxic recovery 
AB  - Glucose and lactate metabolism were studied in a hypoxia-resistant subterranean
      crustacean, Niphargus virei, using an injection of l-[U-14C]lactate and tracer d
      [6-3H]glucose either in normoxic conditions or after a 24 h exposure to severe
      hypoxic. Post-hypoxic animals (H animals) were compared with two treatment groups
      of normoxic animals. In the first normoxic group (NLL animals), animals were
      simultaneously injected with labelled and unlabelled lactate to obtain a lactate
      load similar to that of H animals. In the second normoxic group (N, control
      animals), animals were only injected with labelled lactate. During a 24 h
      recovery period, the incorporation of 14C and 3H into glycogen, lactate, glucose,
      amino acids, lipids and CO2 was measured. During recovery, glucose turnover rate
      was enhanced in H and depressed in NLL compared with N animals. However, when
      energy expenditure was taken into account, the changes were due only to a
      reduction of glucose turnover rate by lactate load. It was concluded that
      gluconeogenesis was not the main source of glyconeogenesis. Equivalent lactate
      loading in NLL and H animals resulted in an equivalent enhancement (fivefold) of
      lactate utilization in both groups when energy expenditure was taken into
      account. Lactate label incorporation appeared later in glycogen than in glucose,
      but remained high 24 h after the injection. Since glucose is mainly an
      extracellular metabolite, this observation may be consistent with the hypothesis
      of two distinct sites for glycogen restoration in hypogean crustaceans: a
      gluconeogenic organ (a liver equivalent) and a glyconeogenic organ (a muscle
      equivalent). The oxidative pathways of glucose and lactate were depressed in post
      hypoxic N. virei and to a lesser extent in the NLL group. Since there is no
      evidence of marked protein utilization, it is postulated that, during recovery,
      repayment of the O2 debt relies on an increase in lipid utilization. During
      recovery from severe hypoxia or after a lactate load, the subterranean N. virei
      appeared to implement a strategy of lactate removal quite different from that
      observed in epigean crustaceans, favouring lactate-supported gluco- and
      glyconeogenesis and rapid glycogen replenishment instead of rapid lactate removal
      via oxidative pathways.

PMID- 9929461
TI  - The force-velocity properties of a crustacean muscle during lengthening 
AB  - Muscle force during active lengthening was characterized for scaphognathite
      levator muscle L2B from the crab Carcinus maenas. The muscle was tetanically
      stimulated and, during the peak of the contraction, stretched at constant
      velocity. The total strain was approximately 4 %, the strain rates ranged from
      0.03 to 1.6 muscle lengths s-1 (L s-1), and the temperature was 15 degreesC.
      Force increased throughout stretch. During low-velocity stretch, up to
      approximately 0.3 L s-1, force rose during isovelocity stretch along an
      approximately exponential trajectory. The asymptotic force approached during the
      stretch increased and the time constant of the response decreased with increasing
      strain rate. With stretch at 0.6 L s-1 and greater, the force increased to a
      distinct yield point, reached after a strain of approximately 1 %, after which
      force continued to increase but with a slope approximately one-quarter as great
      as that before yield. Because force changes continuously during constant-velocity
      lengthening, the adequate descriptor for the force-velocity relationship in a
      lengthening crab muscle is not a two-dimensional force-velocity curve, but rather
      a three-dimensional force-velocity-time or force-velocity-strain surface.
      Stimulating muscle L2B at 20 Hz or 50 Hz gives a smoothly fused tetanic
      contraction in which muscle activation is only partial and the plateau force
      reached is less than that at the optimum stimulus frequency of approximately 100
      Hz. The force-velocity relationships of a partially activated muscle are not
      simply those of a fully activated one scaled down in proportion to the reduction
      in the maximum isometric force. At low stretch velocities, the asymptotic force
      approached is larger in proportion to the pre-stretch isometric tension, and the
      time constant of the force increase is greater, in partially activated than in
      fully activated muscles. At high stretch velocities, the force at yield relative
      to the pre-stretch force, and the relative values of the slopes of the force
      increase before and after yield, are all greater in partially activated than in
      fully activated muscles, while the strain at yield is smaller.

PMID- 9929462
TI  - Does behavioural hypothermia promote post-exercise recovery in cold-submerged
      frogs? 
AB  - At the low temperatures of the overwintering environment of the frog Rana
      temporaria, small changes in ambient temperature have large effects on metabolism
      and behaviour, especially since Q10 values are often greatly elevated in the
      cold. How the overwintering aquatic frog copes with variable thermal environments
      in terms of its overall activity metabolism and recovery from pursuit by
      predators is poorly understood, as is the role of behavioural thermoregulation in
      furthering recovery from intense activity. Exhaustive exercise was chosen as the
      method of evaluating activity capacity (defined by time to exhaustion, total
      distance swum and number of leg contractions before exhaustion) and was
      determined at 1.5 and 7 degreesC. Other cohorts of frogs were examined at both
      temperatures to determine the metabolic (acid-base, lactate, glucose, ATP and
      creatine phosphate) and respiratory responses to exercise in cold-submerged
      frogs. Finally, temperature preference before and after exercise was determined
      in a thermal gradient to define the importance of behavioural thermoregulation on
      the recovery rates of relevant metabolic and respiratory processes. Activity
      capacity was significantly reduced in frogs exercised at 1.5 versus 7 degreesC,
      although similar levels of tissue acid-base metabolites and lactate were reached.
      Blood pH, plasma PCO2 and lactate levels recovered more rapidly at 1.5 degreesC
      than at 7 degreesC; however, intracellular pH and the recovery of tissue
      metabolite levels were independent of temperature. Resting aerobic metabolic
      rates were strongly affected by temperature (Q10=3.82); however, rates determined
      immediately after exercise showed a reduced temperature sensitivity (Q10=1.67)
      and, therefore, a reduced factorial aerobic scope. Excess oxygen consumption
      recovered to resting values after 5-6.25 h, and 67 % recovery times tended to be
      slightly faster at the lower temperatures. Exercise in the cold, therefore,
      provided an immediately higher factorial scope, which could be involved in the
      faster rate of recovery of blood lactate levels in the colder frogs. In addition,
      exercise significantly lowered the preferred temperature of the frogs from 6.7 to
      3.6 degreesC for nearly 7 h, after which they returned to their normal,
      unstressed preferred temperatures. Thus, a transient behavioural hypothermia in
      the skin-breathing, overwintering frog may be an important strategy for
      minimising post-exercise stress and maintaining aerobic metabolism during
      recovery from intense activity.

PMID- 9929463
TI  - Immune-mediated alterations in nociceptive sensory function in Aplysia
      californica.
AB  - Nerve injury in Aplysia californica is accompanied by a profound long-lasting
      enhancement of the excitability of nociceptive sensory neurons that have axons in
      injured nerves. It is likely that a variety of signals are involved in triggering
      this injury-induced sensory plasticity. The objective of the present study was to
      determine whether cells of the cellular defense system (hemocytes) play a role in
      the modulation of sensory excitability following injury. In support of such an
      idea, we have shown previously that the induction of a cellular defense reaction
      close to sensory axons is accompanied by an increase in the excitability of
      sensory neurons with axons close to responding hemocytes. Furthermore, in the
      present study, we verified that, following axonal crush, numerous hemocytes
      accumulate at the injured site on the nerve. Using a hemocyte/nervous system co
      culture preparation, we found that there were no significant differences in the
      expression of injury-induced sensory plasticity between sensory neurons incubated
      in the presence or absence of hemocytes. To overcome some potential limitations
      of our co-culture preparation, we used the endotoxin lipopolysaccharide (LPS) as
      a tool to activate the hemocytes. Sensory cells incubated in the presence of LPS
      and hemocytes were significantly more excitable than sensory cells incubated in
      the presence of LPS alone. We speculate that the addition of LPS to the
      incubation medium containing hemocytes enhanced the release of hemocyte-derived
      cytokine-like factors such as interleukin-1 and tumor necrosis factor. These
      cytokine-like factors may act as signals to modulate the expression of injury
      induced sensory hyperexcitability.

PMID- 9929464
TI  - High-frequency steering maneuvers mediated by tactile cues: antennal wall
      following in the cockroach.
AB  - Cockroaches (Periplaneta americana) use their antennae to detect a wall and to
      maintain a constant distance from it as they walk or run along it. The faster
      they run, the closer they position themselves to the wall. They also use their
      antennae to detect and follow multiple accordion-like projections in the wall.
      They can make up to 25 body turns s-1 for short periods during rapid running to
      follow such wall projections. Each turn apparently involves a change in stepping
      direction. These turns help to avoid collisions with the outward projections,
      while keeping the body close to the wall. Sensory inputs from the flagellum of
      the antenna, and not from its base, appear to evoke the turns in response to wall
      projections. These flagellar inputs appear to report the position along the
      antenna of its contact with the wall and/or the position of the consequent
      antennal bend. This flagellar information constitutes a one-dimensional sensory
      map, with location along the map indicating the distance to the wall.

PMID- 9929465
TI  - Toward a realistic theory of the interaction of membrane inclusions.

PMID- 9929466
TI  - Modeling chemotactic cell sorting during Dictyostelium discoideum mound
      formation.
AB  - Coordinated cell movement is a major mechanism of the multicellular development
      of most organisms. The multicellular morphogenesis of the slime mould
      Dictyostelium discoideum, from single cells into a multicellular fruiting body,
      results from differential chemotactic cell movement. During aggregation cells
      differentiate into prestalk and prespore cells that will form the stalk and
      spores in the fruiting body. These cell types arise in a salt and pepper pattern
      after what the prestalk cells chemotactically sort out to form a tip. The tip
      functions as an organizer because it directs the further development. It has been
      difficult to get a satisfactory formal description of the movement behavior of
      cells in tissues. Based on our experiments, we consider the aggregate as a drop
      of a viscous fluid and show that this consideration is very well suited to
      mathematically describe the motion of cells in the tissue. We show that the
      transformation of a hemispherical mound into an elongated slug can result from
      the coordinated chemotactic cell movement in response to scroll waves of the
      chemoattractant cAMP. The model calculations furthermore show that cell sorting
      can result from differences in chemotactic cell movement and cAMP relay kinetics
      between the two cell types. During this process, the faster moving and stronger
      signaling cells collect on the top of the mound to form a tip. The mound then
      extends into an elongated slug just as observed in experiments. The model is able
      to describe cell movement patterns in the complex multicellular morphogenesis of
      Dictyostelium rather well and we expect that this approach may be useful in the
      modeling of tissue transformations in other systems.

PMID- 9929467
TI  - Amplitude distribution of calcium sparks in confocal images: theory and studies
      with an automatic detection method.
AB  - Determination of the calcium spark amplitude distribution is of critical
      importance for understanding the nature of elementary calcium release events in
      striated muscle. In the present study we show, on general theoretical grounds,
      that calcium sparks, as observed in confocal line scan images, should have a
      nonmodal, monotonic decreasing amplitude distribution, regardless of whether the
      underlying events are stereotyped. To test this prediction we developed,
      implemented, and verified an automated computer algorithm for objective detection
      and measurement of calcium sparks in raw image data. When the sensitivity and
      reliability of the algorithm were set appropriately, we observed highly left
      skewed or monotonic decreasing amplitude distributions in skeletal muscle cells
      and cardiomyocytes, confirming the theoretical predictions. The previously
      reported modal or Gaussian distributions of sparks detected by eye must therefore
      be the result of subjective detection bias against small amplitude events. In
      addition, we discuss possible situations when a modal distribution might be
      observed.

PMID- 9929468
TI  - Exploration of the structural features defining the conduction properties of a
      synthetic ion channel.
AB  - The finite-difference Poisson-Boltzmann methodology was applied to a series of
      parallel, alpha-helical bundle models of the designed ion channel peptide Ac
      (LSSLLSL)3-CONH2. This method is able to fully describe the current-voltage
      curves for this channel and quantitatively explains their cation selectivity and
      rectification. We examined a series of energy-minimized models representing
      different aggregation states, side-chain rotamers, and helical rotations, as well
      as an ensemble of structures from a molecular dynamics trajectory. Potential
      energies were computed for single, permeating K+ and Cl- ions at a series of
      positions along a central pathway through the models. A variable-electric-field
      Nernst-Planck electrodiffusion model was used, with two adjustable parameters
      representing the diffusion coefficients of K+ and Cl- to scale the individual ion
      current magnitudes. The ability of a given DelPhi potential profile to fit the
      experimental data depended strongly on the magnitude of the desolvation of the
      permeating ion. Below a pore radius of 3.8 A, the predicted profiles showed large
      energy barriers, and the experimental data could be fit only with unrealistically
      high values for the K+ and Cl- diffusion coefficients. For pore radii above 3.8
      A, the desolvation energies were 2kT or less. The electrostatic calculations were
      sensitive to positioning of the Ser side chains, with the best fits associated
      with maximum exposure of the Ser side-chain hydroxyls to the pore. The backbone
      component was shown to be the major source of asymmetry in the DelPhi potential
      profiles. Only two of the energy-minimized structures were able to explain the
      experimental data, whereas an average of the dynamics structures gave excellent
      agreement with experimental results. Thus this method provides a promising
      approach to prediction of current-voltage curves from three-dimensional
      structures of ion channel proteins.

PMID- 9929469
TI  - Structure-function study on a de novo synthetic hydrophobic ion channel.
AB  - Ion conduction properties of a de novo synthesized channel, formed from cyclic
      octa-peptides consisting of four alternate L-alanine (Ala) and N'-acylated 3
      aminobenzoic acid (Aba) moieties, were studied in bilayer membranes. The single
      channel conductance was 9 pS in symmetrical 500 mM KCl. The channel favored
      permeation of cations over anions with a permeability ratio (PCl-/PK+) of 0.15.
      The selectivity sequence among monovalent cations based on permeability ratio
      (PX+/PK+) fell into an order: NH4+(1.4) > Cs+(1. 1) >/= K+(1.0) > Na+(0.4) >>
      Li+(0). The conductance-activity relationship of the channel in K+ solutions
      followed simple Michaelis-Menten kinetics with a half-maximal saturating activity
      of 8 mM and a maximal conductance of 9 pS. The permeability ratio PNa+/PK+
      remained constant ( approximately 0.40) under biionic concentrations from 10 to
      500 mM. These results suggests that the channel is a one-ion channel. The pore
      diameter probed by a set of organic cations was approximately 6 A. The single
      channel current was blocked by Ca2+ in a dose-dependent manner that followed a
      single-site titration curve with a voltage-dependent dissociation constant of 0.6
      mM at 100 mV. The electric distance of the binding site for Ca2+ was 0.07 from
      both entrances of the channel, indicating the presence of two symmetrical binding
      sites in each vicinity of the channel entrance. Correlations between conduction
      properties and structural aspects of the channel are discussed in terms of a
      three-barrier and two-binding-site (3B2S) model of Eyring rate theory. All
      available structural information supported an idea that the channel was formed
      from a tail-to-tail associated dimer of the molecule, the pore of which was lined
      with hydrophobic acyl chains. This is the first report to have made a systematic
      analysis of ion permeation through a hydrophobic pore.

PMID- 9929470
TI  - A lattice relaxation algorithm for three-dimensional Poisson-Nernst-Planck theory
      with application to ion transport through the gramicidin A channel.
AB  - A lattice relaxation algorithm is developed to solve the Poisson-Nernst-Planck
      (PNP) equations for ion transport through arbitrary three-dimensional volumes.
      Calculations of systems characterized by simple parallel plate and cylindrical
      pore geometries are presented in order to calibrate the accuracy of the method. A
      study of ion transport through gramicidin A dimer is carried out within this PNP
      framework. Good agreement with experimental measurements is obtained. Strengths
      and weaknesses of the PNP approach are discussed.

PMID- 9929471
TI  - Ca2+ sparks in embryonic mouse skeletal muscle selectively deficient in
      dihydropyridine receptor alpha1S or beta1a subunits.
AB  - Ca2+ sparks are miniature Ca2+ release events from the sarcoplasmic reticulum of
      muscle cells. We examined the kinetics of Ca2+ sparks in excitation-contraction
      uncoupled myotubes from mouse embryos lacking the beta1 subunit and mdg embryos
      lacking the alpha1S subunit of the dihydropyridine receptor. Ca2+ sparks occurred
      spontaneously without a preferential location in the myotube. Ca2+ sparks had a
      broad distribution of spatial and temporal dimensions with means much larger than
      those reported in adult muscle. In normal myotubes (n = 248 sparks), the peak
      fluorescence ratio, DeltaF/Fo, was 1.6 +/- 0.6 (mean +/- SD), the full spatial
      width at half-maximal fluorescence (FWHM) was 3.6 +/- 1.1 micrometer and the full
      duration of individual sparks, Deltat, was 145 +/- 64 ms. In beta-null myotubes
      (n = 284 sparks), DeltaF/Fo = 1.9 +/- 0.4, FWHM = 5.1 +/- 1.5 micrometer, and
      Deltat = 168 +/- 43 ms. In mdg myotubes (n = 426 sparks), DeltaF/Fo = 1 +/- 0.5,
      the FWHM = 2.5 +/- 1.1 micrometer, and Deltat = 97 +/- 50 ms. Thus, Ca2+ sparks
      in mdg myotubes were significantly dimmer, smaller, and briefer than Ca2+ sparks
      in normal or beta-deficient myotubes. In all cell types, the frequency of sparks,
      DeltaF/Fo, and FWHM were gradually decreased by tetracaine and increased by
      caffeine. Both results confirmed that Ca2+ sparks of resting embryonic muscle
      originated from spontaneous openings of ryanodine receptor channels. We conclude
      that dihydropyridine receptor alpha1S and beta1 subunits participate in the
      control of Ca2+ sparks in embryonic skeletal muscle. However, excitation
      contraction coupling is not essential for Ca2+ spark formation in these cells.

PMID- 9929472
TI  - Simultaneous induction of pathway-specific potentiation and depression in
      networks of cortical neurons.
AB  - Activity-dependent modification of synaptic efficacy is widely recognized as a
      cellular basis of learning, memory, and developmental plasticity. Little is
      known, however, of the consequences of such modification on network activity.
      Using electrode arrays, we examined how a single, localized tetanic stimulus
      affects the firing of up to 72 neurons recorded simultaneously in cultured
      networks of cortical neurons, in response to activation through 64 different test
      stimulus pathways. The same tetanus produced potentiated transmission in some
      stimulus pathways and depressed transmission in others. Unexpectedly, responses
      were homogeneous: for any one stimulus pathway, neuronal responses were either
      all enhanced or all depressed. Cross-correlation of responses with the responses
      elicited through the tetanized site revealed that both enhanced and depressed
      responses followed a common principle: activity that was closely correlated
      before tetanus with spikes elicited through the tetanized pathway was enhanced,
      whereas activity outside a 40-ms time window of correlation to tetanic pathway
      spikes was depressed. Response homogeneity could result from pathway-specific
      recurrently excitatory circuits, whose gain is increased or decreased by the
      tetanus, according to its cross-correlation with the tetanized pathway response.
      The results show how spatial responses following localized tetanic stimuli,
      although complex, can be accounted for by a simple rule for activity-dependent
      modification.

PMID- 9929474
TI  - Analysis of dynamic brain imaging data.
AB  - Modern imaging techniques for probing brain function, including functional
      magnetic resonance imaging, intrinsic and extrinsic contrast optical imaging, and
      magnetoencephalography, generate large data sets with complex content. In this
      paper we develop appropriate techniques for analysis and visualization of such
      imaging data to separate the signal from the noise and characterize the signal.
      The techniques developed fall into the general category of multivariate time
      series analysis, and in particular we extensively use the multitaper framework of
      spectral analysis. We develop specific protocols for the analysis of fMRI,
      optical imaging, and MEG data, and illustrate the techniques by applications to
      real data sets generated by these imaging modalities. In general, the analysis
      protocols involve two distinct stages: "noise" characterization and suppression,
      and "signal" characterization and visualization. An important general conclusion
      of our study is the utility of a frequency-based representation, with short,
      moving analysis windows to account for nonstationarity in the data. Of particular
      note are 1) the development of a decomposition technique (space-frequency
      singular value decomposition) that is shown to be a useful means of
      characterizing the image data, and 2) the development of an algorithm, based on
      multitaper methods, for the removal of approximately periodic physiological
      artifacts arising from cardiac and respiratory sources.

PMID- 9929473
TI  - Homology modeling of cephalopod lens S-crystallin: a natural mutant of sigma
      class glutathione transferase with diminished endogenous activity.
AB  - The soluble S-crystallin constitutes the major lens protein in cephalopods. The
      primary amino acid sequence of S-crystallin shows an overall 41% identity with
      the digestive gland sigma-class glutathione transferase (GST) of cephalopod.
      However, the lens S-crystallin fails to bind to the S-hexylglutathione affinity
      column and shows very little GST activity in the nucleophilic aromatic
      substitution reaction between GSH and 1-chloro-2,4-dinitrobenzene. When compared
      with other classes of GST, the S-crystallin has an 11-amino acid residues
      insertion between the conserved alpha4 and alpha5 helices. Based on the crystal
      structure of squid sigma-class GST, a tertiary structure model for the octopus
      lens S-crystallin is constructed. The modeled S-crystallin structure has an
      overall topology similar to the squid sigma-class GST, albeit with longer alpha4
      and alpha5 helical chains, corresponding to the long insertion. This insertion,
      however, makes the active center region of S-crystallin to be in a more closed
      conformation than the sigma-class GST. The active center region of S-crystallin
      is even more shielded and buried after dimerization, which may explain for the
      failure of S-crystallin to bind to the immobilized-glutathione in affinity
      chromatography. In the active site region, the electrostatic potential surface
      calculated from the modeled structure is quite different from that of squid GST.
      The positively charged environment, which contributes to stabilize the negatively
      charged Meisenheimer complex, is altered in S-crystallin probably because of
      mutation of Asn99 in GST to Asp101 in S-crystallin. Furthermore, the important
      Phe106 in authentic GST is changed to His108 in S-crystallin. Combining the
      topological differences as revealed by computer graphics and sequence variation
      at these structurally relevant residues provide strong structural evidences to
      account for the much decreased GST activity of S-crystallin as compared with the
      authentic GST of the digestive gland.

PMID- 9929475
TI  - Single-molecule imaging of RNA polymerase-DNA interactions in real time.
AB  - Using total internal reflection fluorescence microscopy, we have directly
      observed individual interactions of single RNA polymerase molecules with a single
      molecule of lambda-phage DNA suspended in solution by optical traps. The
      interactions of RNA polymerase molecules were not homogeneous along DNA. They
      dissociated slowly from the positions of the promoters and sequences common to
      promoters at a rate of approximately 0.66 s-1, which was more than severalfold
      smaller than the rate at other positions. The association rate constant for the
      slow dissociation sites was 9.2 x 10(2) bp-1 M-1 s-1. The frequency of binding to
      the fast dissociation sites was dependent on the A-T composition; it was larger
      in the AT-rich regions than in the GC-rich regions. RNA polymerase molecules on
      the fast dissociation sites underwent linear diffusion (sliding) along DNA. The
      binding to the slow dissociation sites was greatly enhanced when DNA was released
      to a relaxed state, suggesting that the binding depended on the strain exerted on
      the DNA. The present method is potentially applicable to the examination of a
      wide variety of protein-nucleic acid interactions, especially those involved in
      the process of transcription.

PMID- 9929476
TI  - A physical approach to reduce nonspecific adhesion in molecular recognition
      atomic force microscopy.
AB  - Atomic force microscopy is one of the few techniques that allow analysis of
      biological recognition processes at the single-molecule level. A major limitation
      of this approach is the nonspecific interaction between the force sensor and
      substrate. We have modeled the nonspecific interaction by looking at the
      interaction potential between a conical Si3N4 tip with a spherical end face and a
      mica surface in solution, using DLVO (Derjaguin, Landau, Verwey, Overbeek) theory
      and numerical calculations. Insertion of the tip-sample potential in a simulation
      of an approach-retract cycle of the cantilever gives the well-known force
      distance curve. Simulating a force-distance curve at low salt concentration
      predicts a discrete hopping of the tip, caused by thermal fluctuations. This
      hopping behavior was observed experimentally and gave rise to a novel approach to
      making measurements in adhesion mode that essentially works in the repulsive
      regime. The distance between tip and sample will still be small enough to allow
      spacer-involved specific interactions, and the percentage of nonspecific
      interactions of the bare tip with the mica is minimized. We have validated this
      physical model by imaging intercellular adhesion molecule 1 (ICAM-1) antigen with
      a tip functionalized with anti-ICAM-1 antibody. The measurement demonstrated that
      a significant decrease in the number of nonspecific interactions was realized,
      and the topographical image quality and the specific bonding capability of the
      tip were not affected.

PMID- 9929477
TI  - Transient and long-lasting openings of the mitochondrial permeability transition
      pore can be monitored directly in intact cells by changes in mitochondrial
      calcein fluorescence.
AB  - The occurrence and the mode of opening of the mitochondrial permeability
      transition pore (MTP) were investigated directly in intact cells by monitoring
      the fluorescence of mitochondrial entrapped calcein. When MH1C1 cells and
      hepatocytes were loaded with calcein AM, calcein was also present within
      mitochondria, because (i) its mitochondrial signal was quenched by the addition
      of tetramethylrhodamine methyl ester and (ii) calcein-loaded mitochondria could
      be visualized after digitonin permeabilization. Under the latter condition, the
      addition of Ca2+ induced a prompt and massive release of the accumulated calcein,
      which was prevented by CsA, indicating that calcein release could, in principle,
      probe MTP opening in intact cells as well. To study this process, we developed a
      procedure by which the cytosolic calcein signal was quenched by Co2+. In
      hepatocytes and MH1C1 cells coloaded with Co2+ and calcein AM, treatment with MTP
      inducers caused a rapid, though limited, decrease in mitochondrial calcein
      fluorescence, which was significantly reduced by CsA. We also observed a constant
      and spontaneous decrease in mitochondrial calcein fluorescence, which was
      completely prevented by CsA. Thus MTP likely fluctuates rapidly between open and
      closed states in intact cells.

PMID- 9929478
TI  - Modeling study of the effects of overlapping Ca2+ microdomains on
      neurotransmitter release.
AB  - Although single-channel Ca2+ microdomains are capable of gating neurotransmitter
      release in some instances, it is likely that in many cases the microdomains from
      several open channels overlap to activate vesicle fusion. We describe a
      mathematical model in which transmitter release is gated by single or overlapping
      Ca2+ microdomains produced by the opening of nearby Ca2+ channels. This model
      accounts for the presence of a mobile Ca2+ buffer, provided either that the
      buffer is unsaturable or that it is saturated near an open channel with Ca2+
      binding kinetics that are rapid relative to Ca2+ diffusion. We show that the
      release time course is unaffected by the location of the channels (at least for
      distances up to 50 nm), but paired-pulse facilitation is greater when the
      channels are farther from the release sites. We then develop formulas relating
      the fractional release following selective or random channel blockage to the
      cooperative relationship between release and the presynaptic Ca2+ current. These
      formulas are used with the transmitter release model to study the dependence of
      this form of cooperativity, which we call Ca2+ current cooperativity, on mobile
      buffers and on the local geometry of Ca2+ channels. We find that Ca2+ current
      cooperativity increases with the number of channels per release site, but is
      considerably less than the number of channels, the theoretical upper bound. In
      the presence of a saturating mobile buffer the Ca2+ current cooperativity is
      greater, and it increases more rapidly with the number of channels. Finally, Ca2+
      current cooperativity is an increasing function of channel distance, particularly
      in the presence of saturating mobile buffer.

PMID- 9929479
TI  - Molecular theory of lipid-protein interaction and the Lalpha-HII transition.
AB  - We present a molecular-level theory for lipid-protein interaction and apply it to
      the study of lipid-mediated interactions between proteins and the protein-induced
      transition from the planar bilayer (Lalpha) to the inverse-hexagonal (HII) phase.
      The proteins are treated as rigid, membrane-spanning, hydrophobic inclusions of
      different size and shape, e.g., "cylinder-like," "barrel-like," or "vase-like."
      We assume strong hydrophobic coupling between the protein and its neighbor
      lipids. This means that, if necessary, the flexible lipid chains surrounding the
      protein will stretch, compress, and/or tilt to bridge the hydrophobic thickness
      mismatch between the protein and the unperturbed bilayer. The system free energy
      is expressed as an integral over local molecular contributions, the latter
      accounting for interheadgroup repulsion, hydrocarbon-water surface energy, and
      chain stretching-tilting effects. We show that the molecular interaction
      constants are intimately related to familiar elastic (continuum) characteristics
      of the membrane, such as the bending rigidity and spontaneous curvature, as well
      as to the less familiar tilt modulus. The equilibrium configuration of the
      membrane is determined by minimizing the free energy functional, subject to
      boundary conditions dictated by the size, shape, and spatial distribution of
      inclusions. A similar procedure is used to calculate the free energy and
      structure of peptide-free and peptide-rich hexagonal phases. Two degrees of
      freedom are involved in the variational minimization procedure: the local length
      and local tilt angle of the lipid chains. The inclusion of chain tilt is
      particularly important for studying noncylindrical (for instance, barrel-like)
      inclusions and analyzing the structure of the HII lipid phase; e.g., we find that
      chain tilt relaxation implies strong faceting of the lipid monolayers in the
      hexagonal phase. Consistent with experiment, we find that only short peptides
      (large negative mismatch) can induce the Lalpha --> HII transition. At the
      transition, a peptide-poor Lalpha phase coexists with a peptide-rich HII phase.

PMID- 9929480
TI  - (In)validity of the constant field and constant currents assumptions in theories
      of ion transport.
AB  - Constant electric fields and constant ion currents are often considered in
      theories of ion transport. Therefore, it is important to understand the validity
      of these helpful concepts. The constant field assumption requires that the charge
      density of permeant ions and flexible polar groups is virtually voltage
      independent. We present analytic relations that indicate the conditions under
      which the constant field approximation applies. Barrier models are frequently
      fitted to experimental current-voltage curves to describe ion transport. These
      models are based on three fundamental characteristics: a constant electric field,
      negligible concerted motions of ions inside the channel (an ion can enter only an
      empty site), and concentration-independent energy profiles. An analysis of those
      fundamental assumptions of barrier models shows that those approximations require
      large barriers because the electrostatic interaction is strong and has a long
      range. In the constant currents assumption, the current of each permeating ion
      species is considered to be constant throughout the channel; thus ion pairing is
      explicitly ignored. In inhomogeneous steady-state systems, the association rate
      constant determines the strength of ion pairing. Among permeable ions, however,
      the ion association rate constants are not small, according to modern diffusion
      limited reaction rate theories. A mathematical formulation of a constant currents
      condition indicates that ion pairing very likely has an effect but does not
      dominate ion transport.

PMID- 9929481
TI  - Kramers' diffusion theory applied to gating kinetics of voltage-dependent ion
      channels.
AB  - Kramers' diffusion theory of reaction rates in the condensed phase is considered
      as an alternative to the traditional discrete-state Markov (DSM) model in
      describing ion channel gating current kinetics. Diffusion theory can be expected
      to be particularly relevant in describing high-frequency (>100 kHz) events in
      channel activation. The generalized voltage sensor of a voltage-dependent ion
      channel is treated as a Brownian motion particle undergoing spatial diffusion
      along a one-dimensional energy landscape. Two classes of energy landscapes are
      considered. The first class contains large barriers, which give rise to gating
      currents with two distinct time scales: the usual low-frequency decay, which can
      modeled with a DSM scheme, and a high-frequency component arising from intrastate
      relaxation. Large depolarizations reduce potential barriers to such a degree that
      activation rates are diffusion limited, causing the two time scales to merge.
      Landscapes of the second class are either featureless or contain barriers that
      are small compared to kT; these are termed "drift landscapes." These landscapes
      require a larger friction coefficient to generate slow gating kinetics. The high
      frequency component that appears with barrier models is not present in pure drift
      motion. The presence of a high-frequency component can be tested experimentally
      with large-bandwidth recordings of gating currents. Topics such as frequency
      domain analysis, spatial dependence of the friction coefficient, methods for
      determining the adequacy of a DSM model, and the development of physical models
      of gating are explored.

PMID- 9929482
TI  - Meningococcal PorA/C1, a channel that combines high conductance and high
      selectivity.
AB  - Class 1 porins (PorA/C1) from Neisseria meningitidis achieve both high
      selectivity and high conductance. The channel is highly selective (24:1 Na+ over
      Cl-), suggesting a highly negatively charged selectivity filter. The trimeric
      nature of PorA/C1 accounts for part of the enormous conductance in 200 mM NaCl
      (0.97nS). However, the currents that can be achieved exceed the simple infinite
      sink calculation for a pore 0.7 nm in radius (estimated from nonelectrolyte
      permeability). The conductance is linear with salt activity from 20 mM to 2.0 M
      NaCl with no sign of saturation at low salt. Impermeant polymers reduce the
      conductance in a manner consistent with their ability to reduce bulk
      conductivity. Extrapolating from the known structure of homologous porins, the
      selectivity filter is likely to be small and localized. If small and highly
      negatively charged ( approximately 9 charges), the predicted conductance would be
      an order of magnitude higher than that observed. The rate at which ions reach the
      selectivity filter seems to limit overall ionic flux. PorA/C1 rectifies strongly,
      and this rectification can be accounted for by calculated differences in the
      voltage and concentration profiles in the access regions. Thus, it appears that
      the conductance of this channel is determined by the access resistance and the
      selectivity by a highly-conductive filter.

PMID- 9929483
TI  - Charge translocation by the Na+/K+-ATPase investigated on solid supported
      membranes: rapid solution exchange with a new technique.
AB  - Adsorption of Na+/K+-ATPase containing membrane fragments from pig kidney to
      lipid membranes allows the detection of electrogenic events during the Na+/K+
      ATPase reaction cycle with high sensitivity and time resolution. High stability
      preparations can be obtained using solid supported membranes (SSM) as carrier
      electrodes for the membrane fragments. The SSMs are prepared using an alkanethiol
      monolayer covalently linked to a gold surface on a glass substrate. The
      hydrophobic surface is covered with a lipid monolayer (SAM, self-assembled
      monolayer) to obtain a double layer system having electrical properties similar
      to those of unsupported bilayer membranes (BLM). As we have previously shown (,
      Biophys. J. 64:384-391), the Na+/K+-ATPase on a SSM can be activated by
      photolytic release of ATP from caged ATP. In this publication we show the first
      results of a new technique which allows rapid solution exchange at the membrane
      surface making use of the high mechanical stability of SSM preparations.
      Especially for substrates, which are not available as a caged substance-such as
      Na+ and K+-this technique is shown to be capable of yielding new results. The
      Na+/K+-ATPase was activated by rapid concentration jumps of ATP and Na+ (in the
      presence of ATP). A time resolution of up to 10 ms was obtained in these
      experiments. The aim of this paper is to present the new technique together with
      the first results obtained from the investigation of the Na+/K+-ATPase. A
      comparison with data taken from the literature shows considerable agreement with
      our experiments.

PMID- 9929484
TI  - Charge translocation by the Na+/K+-ATPase investigated on solid supported
      membranes: cytoplasmic cation binding and release.
AB  - In the preceding publication (. Biophys. J. 76:000-000) a new technique was
      described that was able to produce concentration jumps of arbitrary ion species
      at the surface of a solid supported membrane (SSM). This technique can be used to
      investigate the kinetics of ion translocating proteins adsorbed to the SSM.
      Charge translocation of the Na+/K+-ATPase in the presence of ATP was
      investigated. Here we describe experiments carried out with membrane fragments
      containing Na+/K+-ATPase from pig kidney and in the absence of ATP. Electrical
      currents are measured after rapid addition of Na+. We demonstrate that these
      currents can be explained only by a cation binding process on the cytoplasmic
      side, most probably to the cytoplasmic cation binding site of the Na+/K+-ATPase.
      An electrogenic reaction of the protein was observed only with Na+, but not with
      other monovalent cations (K+, Li+, Rb+, Cs+). Using Na+ activation of the enzyme
      after preincubation with K+ we also investigated the K+-dependent half-cycle of
      the Na+/K+-ATPase. A rate constant for K+ translocation in the absence of ATP of
      0.2-0.3 s-1 was determined. In addition, these experiments show that K+
      deocclusion, and cytoplasmic K+ release are electroneutral.

PMID- 9929485
TI  - Genetically engineered metal ion binding sites on the outside of a Channel's
      transmembrane beta-barrel.
AB  - We are exploring the ability of genetically engineered versions of the
      Staphylococcus aureus alpha-hemolysin (alphaHL) ion channel to serve as
      rationally designed sensor components for analytes including divalent cations. We
      show here that neither the hemolytic activity nor the single channel current of
      wild-type alphaHL was affected by [Zn(II)] </= 1 mM. Binding sites for the
      divalent cations were formed by altering the number and location of coordinating
      side chains, e.g., histidines and aspartic acids, between positions 126 and 134,
      inclusive. Several mutant alphaHLs exhibited Zn(II)-induced current noise that
      varied with Zn(II) concentration. At a fixed divalent cation concentration, the
      current fluctuation kinetics depended on the analyte type, e.g., Zn(II), Cu(II),
      Ni(II), and Co(II). We also show that the ability of Zn(II) to change the mutant
      channel current suggests that the pore's topology is beta-sheet and that position
      130 is near the turn at the trans mouth. Both conclusions are consistent with the
      crystal structure of WT-alphaHL oligomerized in detergent. Our results, in the
      context of the channel's crystal structure, suggest that conductance blockades
      were caused by Zn(II) binding to the outside surface of the pore. Thus, analyte
      induced current blockades alone might not establish whether an analyte binding
      site is inside a pore.

PMID- 9929486
TI  - Properties of slow, cumulative sodium channel inactivation in rat hippocampal CA1
      pyramidal neurons.
AB  - Sodium channels in the somata and dendrites of hippocampal CA1 pyramidal neurons
      undergo a form of long-lasting, cumulative inactivation that is involved in
      regulating back-propagating action potential amplitude and can influence
      dendritic excitation. Using cell-attached patch-pipette recordings in the somata
      and apical dendrites of CA1 pyramidal neurons, we determined the properties of
      slow inactivation on response to trains of brief depolarizations. We find that
      the amount of slow inactivation gradually increases as a function of distance
      from the soma. Slow inactivation is also frequency and voltage dependent. Higher
      frequency depolarizations increase both the amount of slow inactivation and its
      rate of recovery. Hyperpolarized resting potentials and larger command potentials
      accelerate recovery from slow inactivation. We compare this form of slow
      inactivation to that reported in other cell types, using longer depolarizations,
      and construct a simplified biophysical model to examine the possible gating
      mechanisms underlying slow inactivation. Our results suggest that sodium channels
      can enter slow inactivation rapidly from the open state during brief
      depolarizations or slowly from a fast inactivation state during longer
      depolarizations. Because of these properties of slow inactivation, sodium
      channels will modulate neuronal excitability in a way that depends in a
      complicated manner on the resting potential and previous history of action
      potential firing.

PMID- 9929487
TI  - Enhanced slow inactivation by V445M: a sodium channel mutation associated with
      myotonia.
AB  - Over 20 different missense mutations in the alpha subunit of the adult skeletal
      muscle Na channel have been identified in families with either myotonia (muscle
      stiffness) or periodic paralysis, or both. The V445M mutation was recently found
      in a family with myotonia but no weakness. This mutation in transmembrane segment
      IS6 is novel because no other disease-associated mutations are in domain I. Na
      currents were recorded from V445M and wild-type channels transiently expressed in
      human embryonic kidney cells. In common with other myotonic mutants studied to
      date, fast gating behavior was altered by V445M in a manner predicted to increase
      excitability: an impairment of fast inactivation increased the persistent Na
      current at 10 ms and activation had a hyperpolarized shift (4 mV). In contrast,
      slow inactivation was enhanced by V445M due to both a slower recovery (10 mV left
      shift in beta(V)) and an accelerated entry rate (1.6-fold). Our results provide
      additional evidence that IS6 is crucial for slow inactivation and show that
      enhanced slow inactivation cannot prevent myotonia, whereas previous studies have
      shown that disrupted slow inactivation predisposes to episodic paralysis.

PMID- 9929488
TI  - Bidirectional transepithelial water transport: measurement and governing
      mechanisms.
AB  - In the search for the mechanisms whereby water is transported across biological
      membranes, we hypothesized that in the airways, the hydration of the periciliary
      fluid layer is regulated by luminal-to-basolateral water transport coupled to
      active transepithelial sodium transport. The luminal-to-basolateral (JWL-->B) and
      the basolateral-to-luminal (JWB-->L) transepithelial water fluxes across ovine
      tracheal epithelia were measured simultaneously. The JWL-->B (6.1
      microliter/min/cm2) was larger than JWB-->L (4.5 microliter/min/cm2, p < 0.05, n
      = 30). The corresponding water diffusional permeabilities were PdL-->B = 1.0 x
      10(-4) cm/s and PdB-->L = 7.5 x 10(-5) cm/s. The activation energy (Ea) of JWL-
      >B (11.6 kcal/mol) was larger than the Ea of JWB-->L (6.5 kcal/mol, p < 0.05, n =
      5). Acetylstrophanthidin (100 microM basolateral) reduced JWL-->B from 6.1 to 4.4
      microliter/min/cm2 (p < 0. 05, n = 5) and abolished the PD. Amiloride (10 microM
      luminal) reduced JWL-->B from 5.7 to 3.7 microliter/min/cm2 (p < 0.05, n = 5) and
      reduced PD by 44%. Neither of these agents significantly changed JWB-->L. These
      data indicate that in tracheal epithelia under homeostatic conditions, JWB-->L
      was dominated by diffusion (Ea = 4.6 kcal/mol), whereas approximately 30% of JWL-
      >B was coupled to the active Na+,K+-ATPase pump (Ea = 27 kcal/mol).

PMID- 9929489
TI  - Excitation of central nervous system neurons by nonuniform electric fields.
AB  - The goal of this study was to determine which neural elements are excited by
      microstimulation of the central nervous system. A cable model of a neuron
      including an axon, initial segment, axon hillock, soma, and simplified dendritic
      tree was used to study excitation with an extracellular point source electrode.
      The model reproduced a wide range of experimentally documented extracellular
      excitation patterns. The site of action potential initiation (API) was a function
      of the electrode position, stimulus duration, and stimulus polarity. The axon or
      initial segment was always the site of API at threshold. When the electrode was
      positioned near the cell body, the site of excitation was dependent on the
      stimulus amplitude. With the electrode in close proximity to the neuron, short
      duration cathodic pulses produced lower thresholds with the electrode positioned
      over the axon than over the cell body, and long-duration stimuli produced
      opposite relative thresholds. This result was robust to alterations in either the
      maximum conductances or the intracellular resistivities of the model. The site of
      maximum depolarization was not always an accurate predictor of the site of API,
      and the temporal evolution of the changes in membrane potential played a strong
      role in determining the site of excitation.

PMID- 9929490
TI  - Spring constants for channel-induced lipid bilayer deformations. Estimates using
      gramicidin channels.
AB  - Hydrophobic interactions between a bilayer and its embedded membrane proteins
      couple protein conformational changes to changes in the packing of the
      surrounding lipids. The energetic cost of a protein conformational change
      therefore includes a contribution from the associated bilayer deformation energy
      (DeltaGdef0), which provides a mechanism for how membrane protein function
      depends on the bilayer material properties. Theoretical studies based on an
      elastic liquid-crystal model of the bilayer deformation show that DeltaGdef0
      should be quantifiable by a phenomenological linear spring model, in which the
      bilayer mechanical characteristics are lumped into a single spring constant. The
      spring constant scales with the protein radius, meaning that one can use suitable
      reporter proteins for in situ measurements of the spring constant and thereby
      evaluate quantitatively the DeltaGdef0 associated with protein conformational
      changes. Gramicidin channels can be used as such reporter proteins because the
      channels form by the transmembrane assembly of two nonconducting monomers. The
      monomerleft arrow over right arrow dimer reaction thus constitutes a well
      characterized conformational transition, and it should be possible to determine
      the phenomenological spring constant describing the channel-induced bilayer
      deformation by examining how DeltaGdef0 varies as a function of a mismatch
      between the hydrophobic channel length and the unperturbed bilayer thickness. We
      show this is possible by analyzing experimental studies on the relation between
      bilayer thickness and gramicidin channel duration. The spring constant in
      nominally hydrocarbon-free bilayers agrees well with estimates based on a
      continuum analysis of inclusion-induced bilayer deformations using independently
      measured material constants.

PMID- 9929491
TI  - Binding of adriamycin to liposomes as a probe for membrane lateral organization.
AB  - A stopped-flow spectrofluorometer equipped with a rapid scanning emission
      monochromator was utilized to monitor the binding of adriamycin to phospholipid
      liposomes. The latter process is evident as a decrease in fluorescence emission
      from a trace amount of a pyrene-labeled phospholipid analog (PPDPG, 1-palmitoyl-2
      [(6-pyren-1-yl)]decanoyl-sn-glycero-3-phospho-rac-++ +glyce rol) used as a donor
      for resonance energy transfer to adriamycin. For zwitterionic 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes, fluorescence decay was slow,
      with a half-time t1/2 of approximately 2 s. When the mole fraction of the acidic
      phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), was
      increased to XPG >/= 0.04, the decay of fluorescence became double exponential,
      and an additional, significantly faster process with t1/2 in the range between 2
      and 4 ms was observed. Subsequently, as XPG was increased further, the amplitude
      of the fast process increased, whereas the slower process was attenuated, its
      t1/2 increasing to 20 s. Increasing [NaCl] above 50 mM or [CaCl2] above 150
      microM abolished the fast component, thus confirming this interaction to be
      electrostatic. The critical dependence of the fast component on XPG allows the
      use of this process to probe the organization of acidic phospholipids in
      liposomes. This was demonstrated with 1, 2-palmitoyl-sn-glycero-3-phosphocholine
      (DPPC) liposomes incorporating PPDPG (XPPDPG = 0.03), i.e., conditions where XPG
      in fluid bilayers is below the required threshold yielding the fast component. In
      keeping with the presence of clusters of PPDPG, the fast component was observed
      for gel-state liposomes. At approximately 34 degreesC (i.e., 6 degrees below Tm),
      the slower fluorescence decay also appeared, and it was seen throughout the main
      phase transition region as well as in the liquid-crystalline state. The
      fluorescence decay behavior at temperatures below, above, and at the main phase
      transition temperature is interpreted in terms of thermal density fluctuations
      and an intermediate state between gel and liquid-crystalline states being
      involved in the phospholipid main phase transition. This is the first observation
      of a cluster constituted by acidic phospholipids controlling the membrane
      association of a drug.

PMID- 9929492
TI  - Interaction of cholesterol with sphingomyelins and acyl-chain-matched
      phosphatidylcholines: a comparative study of the effect of the chain length.
AB  - In this study we have synthesized sphingomyelins (SM) and phosphatidylcholines
      (PC) with amide-linked or sn-2 linked acyl chains with lengths from 14 to 24
      carbons. The purpose was to examine how the chain length and degree of
      unsaturation affected the interaction of cholesterol with these phospholipids in
      model membrane systems. Monolayers of saturated SMs and PCs with acyl chain
      lengths above 14 carbons were condensed and displayed a high collapse pressure (
      approximately 70 mN/m). Monolayers of N-14:0-SM and 1(16:0)-2(14:0)-PC had a much
      lower collapse pressure (58-60 mN/m) and monounsaturated SMs collapsed at
      approximately 50 mN/m. The relative interaction of cholesterol with these
      phospholipids was determined at 22 degreesC by measuring the rate of cholesterol
      desorption from mixed monolayers (50 mol % cholesterol; 20 mN/m) to beta
      cyclodextrin in the subphase (1.7 mM). The rate of cholesterol desorption was
      lower from saturated SM monolayers than from chain-matched PC monolayers. In SM
      monolayers, the rate of cholesterol desorption was very slow for all N-linked
      chains, whereas for PC monolayers we could observe higher desorption rates from
      monolayers of longer PCs. These results show that cholesterol interacts favorably
      with SMs (low rate of desorption), whereas its interaction (or miscibility) with
      long chain PCs is weaker. Introduction of a single cis-unsaturation in the N
      linked acyl chain of SMs led to faster rates of cholesterol desorption as
      compared with saturated SMs. The exception was monolayers of N-22:1-SM and N-24:1
      SM from which cholesterol desorbed almost as slowly as from the corresponding
      saturated SM monolayers. The results of this study suggest that cholesterol is
      most likely capable of interacting with all physiologically relevant (including
      long-chain) SMs present in the plasma membrane of cells.

PMID- 9929493
TI  - Correlation between protein kinase C alpha activity and membrane phase behavior.
AB  - Lipid activation of protein kinase C alpha (PKC alpha) was studied by using a
      model mixture containing 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,
      2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS), and 1, 2-dimyristoyl-sn-glycerol
      (1,2-DMG). This lipid mixture was physically characterized by differential
      scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and
      31P-nuclear magnetic resonance (31P-NMR). Based on these techniques, a phase
      diagram was constructed by keeping a constant DMPC/DMPS molar ratio of 4:1 and
      changing the concentration of 1,2-DMG. This phase diagram displayed three regions
      and two compounds: compound 1 (C1), with 45 mol% 1,2-DMG, and compound 2 (C2),
      with 60 mol% 1,2-DMG. When the phase diagram was elaborated in the presence of
      Ca2+ and Mg2+, at concentrations similar to those used in the PKC alpha activity
      assay, the boundaries between the regions changed slightly and C1 had 35 mol% 1,2
      DMG. The activity of PKC alpha was studied at several temperatures and at
      different concentrations of 1,2-DMG, with a maximum of activity reached at 30
      mol% 1,2-DMG and lower values at higher concentrations. In the presence of Ca2+
      and Mg2+, maximum PKC alpha activity occurred at concentrations of 1,2-DMG that
      were close to the boundary in the phase diagram between region 1, where compound
      C1 and the pure phospholipid coexisted in the gel phase, and region 2, where
      compounds C1 and C2 coexisted. These results suggest that the membrane structure
      corresponding to a mixture of 1,2-DMG/phospholipid complex and free phospholipid
      is better able to support the activity of PKC alpha than the 1,2-DMG/phospholipid
      complex alone.

PMID- 9929494
TI  - Effect of protein aggregation in the aqueous phase on the binding of membrane
      proteins to membranes.
AB  - Analysis of the binding of hydrophobic peptides or proteins to membranes
      generally assumes that the solute is monomeric in both the aqueous phase and the
      membrane. Simulations were performed to examine the effect of solute self
      association in the aqueous phase on the binding of monomeric solute to lipid
      vesicles. Aggregation lowered the initial concentration of monomeric solute,
      which was then maintained at a relatively constant value at the expense of the
      aggregated solute, as the lipid concentration was increased. The resultant
      binding isotherm has a more linear initial portion rather than the classic
      hyperbolic shape. Although this shape is diagnostic of solute self-association in
      the aqueous phase, various combinations of values for the membrane partition
      coefficient and the solute self-association constant will generate similar
      isotherms. Data for cytochrome b5 were analyzed and, when the self-association
      constant was estimated by gel filtration, a unique value for the membrane
      partition coefficient was obtained. Thus, to obtain a true partition coefficient
      the state of the solute in the aqueous phase must be known. If the concentration
      of the monomeric solute species in the aqueous phase can be independently
      determined, then, even with heterogeneous aggregates, the true partition
      coefficient can be obtained.

PMID- 9929495
TI  - Experimental evidence for hydrophobic matching and membrane-mediated interactions
      in lipid bilayers containing gramicidin.
AB  - Hydrophobic matching, in which transmembrane proteins cause the surrounding lipid
      bilayer to adjust its hydrocarbon thickness to match the length of the
      hydrophobic surface of the protein, is a commonly accepted idea in membrane
      biophysics. To test this idea, gramicidin (gD) was embedded in 1, 2-dilauroyl-sn
      glycero-3-phosphocholine (DLPC) and 1, 2-myristoyl-sn-glycero-3-phosphocholine
      (DMPC) bilayers at the peptide/lipid molar ratio of 1:10. Circular dichroism (CD)
      was measured to ensure that the gramicidin was in the beta6.3 helix form. The
      bilayer thickness (the phosphate-to-phosphate distance, or PtP) was measured by x
      ray lamellar diffraction. In the Lalpha phase near full hydration, PtP is 30.8 A
      for pure DLPC, 32.1 A for the DLPC/gD mixture, 35.3 A for pure DMPC, and 32.7 A
      for the DMPC/gD mixture. Gramicidin apparently stretches DLPC and thins DMPC
      toward a common thickness as expected by hydrophobic matching. Concurrently,
      gramicidin-gramicidin correlations were measured by x-ray in-plane scattering. In
      the fluid phase, the gramicidin-gramicidin nearest-neighbor separation is 26.8 A
      in DLPC, but shortens to 23.3 A in DMPC. These experiments confirm the conjecture
      that when proteins are embedded in a membrane, hydrophobic matching creates a
      strain field in the lipid bilayer that in turn gives rise to a membrane-mediated
      attractive potential between proteins.

PMID- 9929496
TI  - Analysis of protein and peptide penetration into membranes by depth-dependent
      fluorescence quenching: theoretical considerations.
AB  - Depth-dependent fluorescence quenching in membranes is playing an increasingly
      important role in the determination of the low resolution structure of membrane
      proteins. This paper presents a graphical way of visualizing membrane quenching
      caused by lipid-attached bromines or spin labels with the help of a depth
      dependent fluorescence quenching profile. Two methods are presently available to
      extract information on membrane penetration from quenching: the parallax method
      (PM; ) and distribution analysis (DA; A. S. Biophys. J. 64:290a (Abstr.); A. S.
      Methods Enzymol. 278:462-473). Analysis of various experimental and simulated
      data by these two methods is presented. The effects of uncertainty in the local
      concentration of quenching lipids (due to protein shielding or nonideality in
      lipid mixing), the existence of multiple conformations of membrane-bound protein,
      incomplete binding, and uncertainty in the fluorescence in nonquenching lipid are
      described. Regardless of the analytical form of the quenching profile (Gaussian
      function for DA or truncated parabola for PM), it has three primary
      characteristics: position on the depth scale, area, and width. The most important
      result, not surprisingly, is that one needs three fitting parameters to describe
      the quenching. This will keep the measures of the quenching profile independent
      of each other resulting in the reduction of systematic errors in depth
      determination. This can be achieved by using either DA or a suggested
      modification of the PM that introduces a third parameter related to quenching
      efficiency. Because DA utilizes a smooth fitting function, it offers an advantage
      for the analysis of deeply penetrating probes, where the effects of transleaflet
      quenching should be considered.

PMID- 9929497
TI  - Molecular and physical mechanisms of first-pass extraction.
AB  - This is a report of a symposium held at the March 1997 meeting of the American
      Society for Pharmacology and Therapeutics in San Diego. Our understanding of the
      events that control first-pass drug elimination in humans has increased
      tremendously by two sequential discoveries. First, cytochrome P-450s 3A4 and 5
      are expressed at high concentrations in both hepatocytes and upper intestinal
      enterocytes, and therefore limit the systemic availability of many drugs. Second,
      P-glycoprotein is expressed at the lumenal surface of the intestinal epithelium
      and therefore also acts to oppose the absorption of unchanged drug. The following
      discussion brings together our current understandings of these interrelated
      phenomena to aid a more complete picture of how they may contribute both
      qualitatively and quantitatively to first-pass elimination.

PMID- 9929498
TI  - Inhibitory anti-CYP3A4 peptide antibody: mapping of inhibitory epitope and
      specificity toward other CYP3A isoforms.
AB  - An antipeptide antibody has been produced that recognizes CYP3A4 and exhibits
      greater than 90-95% inhibition on CYP3A4-mediated reactions [Wang RW and Lu AYH
      (1997) Drug Metab Dispos 25:762-767]. The inhibitory epitope of the 21-amino acid
      peptide, corresponding to residues 253 to 273 of CYP3A4, has been identified to
      reside in a 7-amino acid sequence (LEDTQKH: residues 261-267 of CYP3A4). This
      conclusion was based on the reversal of antibody inhibition of testosterone 6beta
      hydroxylation when peptides with overlapping sequence in this region were
      preincubated with the antibody. In immunoblotting analysis, this antibody did not
      recognize CYP3A5 or CYP3A7 in microsomes prepared from baculovirus-infected cells
      containing these two expressed isoforms. In addition, the antipeptide antibody
      did not inhibit testosterone 6beta-hydroxylation or midazolam 1'- and 4
      hydroxylation in microsomes containing expressed CYP3A5 and CYP3A7. Because the
      corresponding sequence in CYP3A5 (LNDKQKH) and CYP3A7 (LKETQKH) differs from
      CYP3A4 by only two amino acids, six peptides with either one or two amino acid
      changes were used to determine which amino acid is essential for antibody-antigen
      interaction. Our data indicate that Glu, Asp, and Thr in the 7-amino acid
      sequence of CYP3A4 are critical determinants of selectivity among CYP3A isoforms.

PMID- 9929499
TI  - Comparison of cytochrome P-450-dependent metabolism and drug interactions of the
      3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in
      the liver.
AB  - In an in vitro study, the cytochrome P-450 3A (CYP3A)-dependent metabolism and
      drug interactions of the 3-hydroxy-3-methylglutaryl-Co A reductase inhibitors
      lovastatin and pravastatin were compared. Lovastatin was metabolized by human
      liver microsomes to two major metabolites: 6'beta-hydroxy [Michaelis-Menten
      constant (Km): 7.8 +/- 2.7 microM] and 6'-exomethylene lovastatin (Km,10.3 +/-
      2.6 microM). 6'beta-Hydroxylovastatin formation in the liver was inhibited by the
      specific CYP3A inhibitors cyclosporine (Ki, 7.6 +/- 2.3 microM), ketoconazole
      (Ki, 0.25 +/- 0.2 microM), and troleandomycin (Ki, 26.6 +/- 18.5 microM).
      Incubation of pravastatin with human liver microsomes resulted in the generation
      of 3'alpha,5'beta, 6'beta-trihydroxy pravastatin (Km, 4,887 +/- 2,185 microM) and
      hydroxy pravastatin (Km, 20,987 +/- 9,389 microM). The formation rates of
      3'alpha,5'beta,6'beta-trihydroxy pravastatin by reconstituted CYP3A enzymes were
      (1,000 microM pravastatin) 1.9 +/- 0.6 pmol.min-1.pmol CYP3A4 and 0.06 +/- 0.04
      pmol.min-1.pmol CYP3A5, and the formation rates of hydroxy pravastatin were 0.12
      +/- 0.02 pmol.min-1.pmol CYP3A4 and 0.02 +/- 0.004 pmol.min-1.pmol CYP3A5. The
      specific CYP3A inhibitors cyclosporine, ketoconazole, and troleandomycin
      significantly inhibited hydroxy pravastatin formation by human liver microsomes,
      but only ketoconazole inhibited 3'alpha, 5'beta,6'beta-trihydroxy pravastatin
      formation, suggesting that other CYP enzymes are involved in its formation. It is
      concluded that, compared with lovastatin [CLint formation 6'beta
      hydroxylovastatin (microl.min-1.mg-1): 199 +/- 248, 6'-exomethylene lovastatin:
      138 +/- 104)], CYP3A-dependent metabolism of pravastatin [CLint formation
      3'alpha,5'beta, 6'beta-trihydroxy pravastatin (microl.min-1.mg-1): 0.03 +/- 0.03
      and hydroxy pravastatin: 0.02 +/- 0.02] is a minor elimination pathway. In
      contrast to lovastatin, drug interactions with pravastatin CYP3A-catalyzed
      metabolism cannot be expected to have a clinically significant effect on its
      pharmacokinetics.

PMID- 9929500
TI  - Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver
      microsomes: comparison of Ki values and impact of CYP3A5 expression.
AB  - The purpose of this study was to compare the kinetics of intestinal and hepatic
      cytochrome P-450 3A (CYP3A) inhibition by using microsomal midazolam 1'
      hydroxylation as a marker of enzyme activity. The effect of two antifungal agents
      commonly implicated in CYP3A drug-drug interactions was examined. Inhibition type
      and affinities were determined for human liver and intestinal microsomes screened
      for the presence or absence of CYP3A4 and CYP3A5, as well as for cDNA-expressed
      CYP3A4 and CYP3A5 microsomes. Ketoconazole and fluconazole were found to be
      noncompetitive inhibitors of both enzymes. Ketoconazole exhibited a Ki for cDNA
      expressed CYP3A4 of 26. 7 +/- 1.71 nM, whereas the Ki for cDNA expressed CYP3A5
      was 109 +/- 19.7 nM. Corresponding Ki values for fluconazole were 9.21 +/- 0.51
      microM and 84.6 +/- 12.9 microM. For liver and intestinal microsomes that
      contained only CYP3A4, the average ketoconazole Ki was found to be 14.9 +/- 6.7
      nM and 17.0 +/- 7.9 nM, respectively, whereas fluconazole yielded mean respective
      Ki values of 10.7 +/- 4.2 microM and 10.4 +/- 2.9 microM. Liver and intestinal
      microsomes that contained an equal or greater amount of CYP3A5, in addition to
      CYP3A4, were less susceptible to inhibition by both ketoconazole and fluconazole.
      These findings suggest that there can be significant differences in the affinity
      of these two enzymes for inhibitors. This may further broaden interindividual
      variability with respect to the magnitude of in vivo drug-drug interactions. We
      also conclude that there is no significant difference in inhibition type and
      affinity of ketoconazole and fluconazole for hepatic versus intestinal CYP3A4.

PMID- 9929501
TI  - Developmental changes in the catalytic activity and expression of CYP2D isoforms
      in the rat liver.
AB  - Developmental changes in bufuralol 1'-hydroxylation activity, which is known as a
      typical activity of cytochrome P-450 (CYP)2D isoforms, in the liver of rats were
      investigated. The catalytic activities of hepatic microsomes increased with
      development especially from 3 to 7 weeks. Eadie-Hofstee plots of bufuralol 1'
      hydroxylation were obtained for monophasic kinetics (Km: 0.037 microM) at 1 week
      and for biphasic kinetics (Km: 0.051 and 6.4 microM) at 7 weeks of age. Quinine
      completely inhibited bufuralol 1'-hydroxylation activity of hepatic microsomes of
      1- and 7-week-old rats. These results indicated that at least two kinds of CYP2D
      isoforms, which differ markedly in their affinity for bufuralol, were present at
      7 weeks of age and that the CYP2D isoform that had low affinity for bufuralol was
      expressed with development. To assess the affinity of CYP2D isoforms for
      bufuralol, the kinetic properties of CYP2D1, 2D2, 2D3, and 2D4 expressed in yeast
      cells were investigated. The Km value of CYP2D2, 0.044 microM, was extremely
      small compared with that of the other rat CYP2D isoforms. We further investigated
      developmental changes of CYP2D isoform mRNA by reverse transcription-polymerase
      chain reaction. CYP2D3 mRNA increased with development although CYP2D1 and 2D2
      mRNA were not changed. The CYP2D4 mRNA was not detected. These findings indicated
      that CYP2D2, which had high affinity for bufuralol, was expressed in immature and
      mature rats, but CYP2D3, which had low affinity for bufuralol, was expressed only
      in mature rats.

PMID- 9929502
TI  - Cytochrome P-450 mRNAs are modulated by dehydroepiandrosterone, nafenopin, and
      triiodothyronine.
AB  - Dehydroepiandrosterone (DHEA) is the only known naturally occurring compound that
      promotes peroxisome proliferation in rodent liver, and stimulates transcriptional
      induction of genes involved in lipid metabolism and peroxisomal beta-oxidation.
      Therefore, we examined mRNA for several such genes in rat liver, specifically
      acyl-CoA oxidase and the cytochromes P-450 (CYP4A1, CYP4A3, and CYP3A23), after 5
      to 6 day treatments with either DHEA, or nafenopin, a known peroxisome
      proliferator. Acyl-CoA oxidase and CYP4A1 were induced nearly identically by DHEA
      and nafenopin, with induction being more pronounced in female rats. However,
      CYP3A23 was induced only by DHEA, suggesting an induction mechanism independent
      of the peroxisome proliferator activated receptor. Previously, we observed
      triiodothyronine (T3) suppression of peroxisome proliferator induced CYP4As and
      we sought to determine whether CYP3A23 might be regulated in a different manner.
      T3 was found to also suppress DHEA-dependent induction of CYP3A23. CYP4A2
      expression in kidney was also negatively regulated by T3. To characterize a
      putative negative thyroid hormone response element (nTRE) in the 5' flanking
      region of this gene, a luciferase reporter gene containing a rat CYP4A2 flanking
      sequence extending to -1865 bp was transfected into HepG2 cells along with human
      thryroid hormone receptor expression vector. Expression of luciferase activity
      was unaffected by T3, suggesting the absence of a functional nTRE within this
      portion of CYP4A2. These data demonstrate gene regulatory activity by DHEA
      different from that of nafenopin, and a suppressive effect of T3, consistent with
      indirect regulatory mechanisms not involving an nTRE.

PMID- 9929503
TI  - A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady
      state.
AB  - Clinical trials with tizanidine when administered alone have shown that 5-chloro
      4-(2-imidazolin-2-ylamino)-2,1,3-benzothiodiazole (tizanidine) is safe and
      effective for spasticity control. However, given its mechanism of action and
      requirement for titration, clinical experience suggests that tizanidine is likely
      to be used in combination with other antispastic agents with different mechanisms
      of action, such as baclofen. The objective of this study was to examine the
      pharmacokinetics of both tizanidine and baclofen under steady-state conditions
      when administered alone or concomitantly. This was a randomized, three-period,
      multiple-dose, Latin Square design study consisting of tizanidine HCl, 4 mg
      t.i.d. for seven consecutive doses; baclofen, 10 mg t.i.d. for seven consecutive
      doses; and both regimens simultaneously for seven consecutive doses. Drug
      administration was performed every 8 h, three times daily. Fifteen normal men
      served as study subjects. A priori, a clinically significant difference was set
      as 30%. Concentrations of tizanidine and baclofen were nearly identical during
      the single and concomitant dosing periods. All of the calculated steady-state
      pharmacokinetic parameter changes for baclofen, tizanidine, and its major
      metabolites were within the 30% criterion. Small differences in renal clearance
      were observed when the two drugs were coadministered, but these changes are
      unlikely to be clinically important. Thus, it is unlikely that coadministration
      of tizanidine and baclofen during dose-titration of the former will result in a
      pharmacokinetic interaction.

PMID- 9929504
TI  - In vivo metabolism of a new anticancer agent, 6-N-formylamino-12, 13-dihydro-1,11
      dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3,4-c]carbazole
      5,7(6H)-dione (NB-506) in rats and dogs: pharmacokinetics, isolation,
      identification, and quantification of metabolites.
AB  - 6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo
      [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of
      DNA topoisomerase I, is currently under development for the treatment of cancer.
      We investigated the pharmacokinetics of NB-506 after i.v. administration in rats
      and dogs. The plasma concentration of NB-506 decreased biexponentially in rats
      and dogs with terminal half-lives of approximately 2 h. The area under the curve
      increased nonlinearly with increasing dose in rats. In contrast, there was a
      linear relationship between the area under the curve and the dose in dogs. In
      rats, the plasma clearance decreased with increasing dose up to 187.5 mg/m2 but
      remained virtually unchanged at the highest dose. The Vdss of NB-506 in rats and
      dogs was much greater than the plasma volume, indicating that NB-506 is highly
      distributed to tissue from plasma in these animals. There were marked species
      differences in the plasma concentrations of ED-501 after i.v. administration of
      NB-506 to rats and dogs. To better understand the mechanisms of nonlinear
      pharmacokinetics in rats, in vivo metabolites were determined. After i.v.
      administration of [14C]NB-506 to rats, two unknown metabolites (RBM-1 and RBM-2),
      deformyl metabolite (ED-501), and unchanged drug (NB-506) were identified. Mass
      and NMR spectra analysis revealed that RBM-1 is an 11-O-glucuronide of NB-506 (ED
      594) and that RBM-2 is an 11-O-glucuronide of ED-501 (ED-595). In this study, the
      pharmacokinetics of NB-506 was demonstrated to be nonlinear in rats, probably
      because of saturation of the enzyme systems catalyzing the deformylation and
      glucuronidation of NB-506 in rats.

PMID- 9929505
TI  - In vitro metabolism of a new anticancer agent, 6-N-formylamino-12, 13-dihydro
      1,11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo+ ++[2,3-a]pyrrolo[3,4
      c]carbazole-5,7(6H)-dione (NB-506), in mice, rats, dogs, and humans.
AB  - The metabolism of 6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D
      glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506),
      a potent inhibitor of DNA topoisomerase I, was characterized in mice, rats, dogs,
      and humans in vitro. NB-506 was deformylated to ED-501 in mouse and rat plasma
      with enzyme activity of 140 and 116 pmol/min/mg protein, respectively. The enzyme
      activity in dog and human plasma was found to be less than 1.7 pmol/min/mg
      protein. In liver S9 and small intestine S9 samples from mice and rats, activity
      of the enzyme was very low. Also, there was no activity in the liver or small
      intestine of dogs and humans. The enzyme involved in the conversion of NB-506 to
      ED-501 in rat plasma is a rodent-specific serine enzyme with a molecular mass of
      138KDa. The Vmax and Km values were 6.3 nmol/min/ml plasma and 54 microM at an
      optimum pH of 7.4, respectively. Although NB-506 was converted to ED-551 in dog
      and human plasma in vitro, no conversion was observed in mouse and rat plasma. In
      human plasma this conversion was not affected by heat treatment (100 degreesC for
      1 min), but was inhibited completely by 50 mM EDTA, indicating that the reaction
      is a chemical reaction catalyzed by metal ions. Although NB-506 was not
      metabolized by cytochrome P-450 isozymes in liver, this drug was glucuronized in
      mice, rats, and humans, but not in dogs. These results suggest that a species
      difference in the metabolism of NB-506 occurred in the liver as well as in
      plasma. There appeared to be species differences in the metabolism of NB-506 in
      vitro, correlating well with the species-dependent pharmacokinetics of this drug
      in vivo.

PMID- 9929506
TI  - Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after
      intravenous and oral administration to rats: hepatic and gastric first-pass
      effects.
AB  - Pharmacokinetic parameters of 2-(allylthio)pyrazine (2-AP) were evaluated after
      i.v. administration of the drug (10, 20, 50, and 100 mg/kg body weight) and oral
      administration of the drug (10, 50, and 100 mg/kg body weight) to rats. The
      hepatic, gastric, and intestinal first-pass effects of 2-AP were also measured
      after i.v., intraportal, intraduodenal, and oral administration of the drug (10
      and 50 mg/kg body weight) to rats. After i.v. administration, the pharmacokinetic
      parameters of 2-AP were dose-independent at the dose ranges studied. However,
      after oral administration, the dosenormalized total area under the plasma
      concentration-time curve from time zero to time infinity values (43.5, 125, and
      205 microg min/ml, based on 10 mg/kg body weight) increased significantly with
      increasing doses. The extent of absolute oral bioavailability (F) values also
      increased with increasing oral doses; the values were 19. 6, 56.7, and 93.6% for
      10, 50, and 100 mg/kg body weight, respectively. The oral data above could be due
      to saturable hepatic, gastric, and/or intestinal first-pass effects. This was
      proved by saturable gastric first-pass effect (the significant area under the
      plasma concentration-time curve from time zero to time infinity difference
      between oral and intraduodenal administration of 2-AP); the values were 62.6 and
      26.6% at 2-AP doses of 10 and 50 mg/kg body weight, respectively. Approximately
      20% of oral dose was eliminated by liver (hepatic first-pass effect) for both
      oral doses of 10 and 50 mg/kg body weight. However, the first-pass effects of 2
      AP in the intestine, heart, and lung were almost negligible. The low F value
      after oral administration of 2-AP at low dose (10 mg/kg body weight) was mainly
      due to gastric first-pass effect in rats.

PMID- 9929507
TI  - High in situ rat intestinal permeability of artemisinin unaffected by multiple
      dosing and with no evidence of P-glycoprotein involvement.
AB  - The objective of this study was to investigate whether the decrease in
      artemisinin bioavailability after repeated oral dosing in humans can be a result
      of increased efflux of artemisinin by P-glycoprotein or decreased membrane
      transport at the intestinal barrier. The effective jejunal permeability (Peff) of
      artemisinin was investigated using an in situ rat perfusion model. Fifty-four
      rats were randomized to one of three treatment arms: no pretreatment,
      pretreatment with artemisinin emulsion for 5 days (60 mg/kg/day, p.o. ), or
      pretreatment with emulsion vehicle for 5 days. The rats within each treatment arm
      were randomized further to be jejunally perfused with either low (500 ng/ml) or
      high (5000 ng/ml) artemisinin concentration or low artemisinin concentration plus
      the P-glycoprotein inhibitor R,S-verapamil (400 microg/ml). Perfusate samples
      were assayed for content of artemisinin, R,S-verapamil, and perfusion viability
      markers. Artemisinin Peff was 1.44 +/- 0.38, 1. 17 +/- 0.32, and 1.71 +/- 0.29
      (.10(-4), cm/s) in rats receiving no pretreatment and perfused with low, high, or
      low artemisinin concentration plus verapamil, respectively. Multiple oral dosing
      of artemisinin did not affect the jejunal permeability of artemisinin. R,S
      verapamil Peff was similar in artemisinin-pretreated rats (1.09 +/- 0.54. 10(-4),
      cm/s) and rats pretreated with only vehicle (1.07 +/- 0.37. 10(-4), cm/s). The
      decrease in artemisinin bioavailability after multiple oral dosing in human is
      probably not a result of changes in P-glycoprotein expression or general
      intestinal transport. It seems more likely attributed to increased hepatocellular
      activity. Furthermore, artemisinin exhibits high jejunal permeability and is
      neither a substrate nor inducer of P-glycoprotein.

PMID- 9929508
TI  - Inactivation of cytochrome P-450 (CYP2E1) and carboxylesterase (hydrolase A)
      enzymes by vinyl carbamate in murine pulmonary microsomes.
AB  - We tested the hypothesis that vinyl carbamate (VC) is metabolized in vitro by
      cytochrome P-450 and carboxylesterase enzymes in murine lung. Incubations with VC
      and an NADPH-generating system produced a 50% decrease in N-nitrosodimethylamine
      (NDMA) demethylation and a corresponding loss in the amounts of immunodetectable
      CYP2E1. Preincubation of microsomes with a CYP2E1 inhibitory antibody or the
      CYP2E1-selective inhibitor diallyl sulfone (DASO2) inhibited demethylase
      activity; no alterations were detected upon subsequent exposure to VC.
      Carboxylesterase-mediated hydrolysis of p-nitrophenyl acetate was reduced by 22%
      in microsomes incubated with VC. Decreased carboxylesterase activity also was
      detected in microsomes incubated with phenylmethylsulfonyl fluoride (PMSF), an
      inhibitor of hydrolase A, a carboxylesterase isozyme. No change in enzyme
      activity was detected when microsomes were subsequently incubated with VC. The
      loss in carboxylesterase activity correlated with decreased immunodetectable
      hydrolase A in microsomes incubated with VC, PMSF, or PMSF and VC. The reduction
      in VC-induced NDMA demethylase activity was increased to 85% of the control in
      microsomes previously incubated with PMSF, and this corresponded with a marked
      decrease in CYP2E1 immunoreactivity in the immunoblots. Covalent binding of VC to
      proteins was detected in microsomes incubated with VC and an NADPH-generating
      system. Binding was inhibited in microsomes preincubated with either an
      inhibitory CYP2E1 antibody or DASO2. In contrast, binding levels were augmented
      in microsomes preincubated with PMSF. These data supported VC metabolism by
      CYP2E1 and hydrolase A in murine lung microsomes and is consistent with
      involvement of CYP2E1 and hydrolase A in the activation and detoxication of VC,
      respectively.

PMID- 9929509
TI  - In vivo metabolism of the antitumor imidazoacridinone C1311 in the mouse and in
      vitro comparison with humans.
AB  - C1311 has emerged as the lead compound from a novel group of anticancer agents,
      the imidazoacridinones, and will be entering clinical trials shortly. Previous
      murine pharmacokinetic studies have shown C1311 to be rapidly and extensively
      distributed into tissues including tumor. This study has identified two major
      metabolites of C1311 and describes their pharmacokinetics in mice. M1 is a
      glucuronide of the parent compound with high concentrations in both plasma and
      liver. Calculated area under the plasma concentration versus time curve values
      were 6-fold and 2-fold greater, respectively, than C1311. Based on these studies,
      we propose M2 to be a nonfluorescent oxidation product because electrospray
      ionization-mass spectroscopy/mass spectroscopy analysis gave a molecular ion at
      m/z 367, 16 U greater than the parent compound. It formed rapidly in liver
      preparations in vitro, both murine and human, by a cytosolic process in the
      presence of NADPH and in vivo was detected in liver tissues at concentrations
      equivalent to those of C1311 but was not detectable in plasma. Preliminary in
      vitro toxicity studies showed M2 to be as potent as C1311 against MAC15A tumor
      cells. Over the first 24 h, 39% of the administered dose is eliminated via the
      bile (28%) mostly as C1311 or the kidneys (11%) as the glucuronide (M1). This
      study has given valuable information as to the likely metabolic pathway to occur
      in humans, and the cytotoxic metabolite M2 may play a role in the antitumor
      activity or toxicity of C1311 in the clinic.

PMID- 9929510
TI  - Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro
      activities of cDNA-expressed human cytochromes P-450.
AB  - The effects of methanol, ethanol, dimethyl sulfoxide (DMSO), and acetonitrile
      were studied in vitro on nine individual, cDNAexpressed cytochrome P-450
      activities (phenacetin O-deethylase for CYP1A1 and CYP1A2, coumarin 7-hydroxylase
      for CYP2A6, testosterone 6beta-hydroxylase for CYP3A4, 7-ethoxy-4
      trifluoromethylcoumarin deethylase for CYP2B6, paclitaxel 6alpha-hydroxylase for
      CYP2C8, diclofenac 4'-hydroxylase for CYP2C9, S-mephenytoin 4-hydroxylase for
      CYP2C19, and (+/-)-bufuralol 1'-hydroxylase for CYP2D6) in commercially available
      human lymphoblastoid microsomes. These data show that specific solvents have
      enzyme-selective effects on P-450 activities. Methanol did not substantially
      inhibit (</=10%) any of the activities at 0.3%, but did inhibit CYP1A1, CYP2B6,
      CYP2C9, and CYP2D6 by 12 to 26% at 1%. In contrast, 0.1% ethanol inhibited
      CYP1A1, CYP2B6, and CYP2C19 by 20 to 30%. Ethanol at 1% did not inhibit CYP1A2,
      CYP3A4, CYP2C8, and CYP2C9. DMSO inhibited CYP3A4, CYP2C19, and CYP2D6 by 15 to
      25% at 0.1%. However, DMSO had little effect on CYP1A2, CYP2A6, and CYP2C8.
      Acetonitrile, like methanol, did not inhibit any P-450 activity at 0.3% solvent
      except for CYP1A1 (26%) and CYP2B6 (13%). At 1%, acetonitrile decreased
      activities of CYP1A1 and CYP2B6 by 40 to 60%, and inhibited CYP2A6, CYP3A4,
      CYP2C19, and CYP2D6 activity by 10 to 20%. Acetonitrile also increased CYP2C9
      activity by 10 to 15% above control values at 1 to 3% solvent. Excluding
      solubility considerations, methanol and acetonitrile appear to be the most
      suitable solvents for the introduction of substances to cytochrome P-450
      incubations for in vitro metabolism studies.

PMID- 9929511
TI  - In vitro evaluation of potential drug interactions with levetiracetam, a new
      antiepileptic agent.
AB  - Levetiracetam and its carboxylic metabolite (AcL) were tested for their potential
      inhibitory effect on 11 different drug metabolizing enzyme activities using human
      liver microsomes. The following specific assays were investigated: testosterone
      6beta-hydroxylation [cytochrome P-450 3A4 (CYP3A4)], coumarin hydroxylation
      (CYP2A6), (R)-warfarin hydroxylation (CYP1A2), (S)-mephenytoin hydroxylation
      (CYP2C19), p-nitrophenol hydroxylation (CYP2E1) tolbutamide hydroxylation
      (CYP2C9), dextromethorphan O-demethylation (CYP2D6), epoxide hydrolase and UDP
      glucuronyltransferase (UGT) toward paracetamol (UGT1*6), ethinyloestradiol
      (UGT1*1), p-nitrophenol (UGT(pl 6.2)), and valproic acid. None of these
      activities were affected by levetiracetam or AcL added at concentrations up to 1
      mM. Additionally, primary cultures of rat hepatocytes were used to assess a
      potential inducing effect of levetiracetam on CYPs. Phenobarbital (2 mM), beta
      naphtoflavone (40 microM), dexamethasone (1 microM), and phenytoin (up to 300
      microM) were tested as positive controls. When added to cells for 48 h, all the
      positive controls increased 7-ethoxycoumarin O-deethylase activity demonstrating
      the inducibility of CYPs in the present culture conditions. By contrast,
      levetiracetam did not affect the activity up to 1 mM. The highest levetiracetam
      concentrations examined in the above in vitro studies are well in excess of those
      measured in the plasma of patients receiving therapeutic doses. It is thus
      concluded that levetiracetam is unlikely to produce pharmacokinetic interactions
      through inhibition of CYPs, UGTs, and epoxide hydrolase. Furthermore, based on
      the in vitro assays with rat hepatocytes, it could be speculated that
      levetiracetam does not act as a CYP inducer.

PMID- 9929512
TI  - Metabolism of 3,5,5-trimethylhexanoyl-ferrocene by rat liver: release of iron
      from 3,5,5-trimethylhexanoyl-ferrocene by a microsomal, phenobarbital-inducible
      cytochrome P-450.
AB  - 3,5,5-Trimethylhexanoyl (TMH)-ferrocene has been used to produce iron loading in
      whole animals and in cultured hepatocytes. Iron loading produced by TMH-ferrocene
      is highly efficient and, of the compounds used to produce iron loading in
      experimental systems, most closely mimics the loading patterns observed in the
      human disease hemochromatosis. Previous work with TMH-ferrocene has shown that
      TMH-ferrocene is degraded in vivo because the iron is released from the ferrocene
      nucleus. Because TMH-ferrocene is highly lipophilic and stable chemically, we
      hypothesize that this molecule indeed could be degraded enzymatically. To measure
      the breakdown of TMH-ferrocene, iron release from the molecule was analyzed using
      a Ferrochem II analyzer, which uses constant potential coulometry to measure the
      amount of ionic iron within a biological sample. In this study, we show that TMH
      ferrocene is degraded by a microsomal enzyme that requires NADPH and molecular
      oxygen. The TMH-ferrocenase activity is heat labile, requires a physiologic
      temperature, is induced by phenobarbital, and is inhibited by carbon monoxide and
      piperonyl butoxide but not by dicoumarol. The enzyme follows Michaelis-Menten
      kinetics and has a Km of 58.5 microM and a Vmax of 57.5 nmol Fe released/mg
      protein/min. We conclude that TMH-ferrocene is degraded by a phenobarbital
      inducible cytochrome P-450.

PMID- 9929513
TI  - Developmental expression of N-acetyltransferases in C57BI/6 mice.
AB  - N-Acetyltransferases (NATs) play an important role in the biotransformation of a
      wide variety of arylamine drugs and carcinogens. Two genes (NAT1, NAT2) have been
      identified and allelic variation in NAT2 has been associated with arylamine
      toxicity in adults. Little information has been reported on expression of NAT
      genes during embryonic and fetal development although substrate specific NAT
      activity has been detected. The current study investigated the expression of NAT1
      and NAT2 in mice pre-and postnatally. RNA was isolated from maternal liver,
      embryonic tissue at gestational days (GD) 10, 15, and 18, or neonates at neonatal
      day 3. Reverse transcription-polymerase chain reaction was performed using
      primers designed to amplify portions of either the NAT1 or the NAT2 gene. NAT1
      and NAT2 mRNAs were detected in the embryo/placental complex at GD 10 and in GD
      15 and 18 embryos. NAT2 but not NAT1 was expressed in GD 18 and neonatal day 3
      hepatic tissue. These data demonstrate the differential expression of NAT genes
      in the mouse embryo and suggest a potential role for NAT in development.

PMID- 9929514
TI  - Relative plasma levels of the cardioprotective drug dexrazoxane and its two
      active ring-opened metabolites in the rat.
AB  - A postcolumn derivatization reversed-phase high-pressure liquid chromatography
      method has been developed to detect and separate the one-ring open intermediates
      of dexrazoxane (ICRF-187) in blood plasma. Dexrazoxane is clinically used as a
      doxorubicin cardioprotective agent and may act by preventing iron-based oxygen
      free radical damage through the iron-chelating ability of its one-ring open
      intermediates and its fully rings opened hydrolysis product ADR-925. Little is
      known of the in vivo metabolism of dexrazoxane to its one-ring open
      intermediates, which may be two of the active forms of dexrazoxane. The one-ring
      open intermediates were detected within 5 min of i.v. administration of
      dexrazoxane to rats, suggesting that dexrazoxane is rapidly metabolized in vivo.
      The plasma concentrations of the one-ring open intermediates varied from 4 to 9%
      and 6 to 24% of the dexrazoxane concentrations at 5 and 120 min, respectively.
      The relatively small changes in the levels of the one-ring open intermediates
      with time suggest that a dynamic steady state is occurring. The ratio of the
      concentrations of the two one-ring open intermediates was similar to that
      previously seen for the in vitro dihydropyrimidine amidohydrolase-catalyzed
      hydrolysis of dexrazoxane. These results are consistent with the hypothesis that
      dihydropyrimidine amidohydrolase in the liver and kidney is responsible for the
      metabolism of dexrazoxane in the rat.

PMID- 9929515
TI  - Characterization of eprinomectin N-deacetylase in rats.
AB  - The enzyme system responsible for the N-deacetylation of eprinomectin in rats was
      characterized. Tissue and subcellular studies showed that the hydrolysis activity
      was localized mainly in liver microsomes. Apparent KM and Vmax values calculated
      from Lineweaver-Burk plots were 53 microM and 0.81 nmol/mg/min for male rats and
      70 microM and 4.99 nmol/mg/min for female rats, respectively. Pretreatment of
      male rats with dexamethasone, phenobarbital, and pregnenolone 16alpha
      carbonitrile increased the activity by more than 3-fold. Paraoxon and bis-4
      nitrophenylphosphate strongly inhibited the deacetylase activity at
      concentrations as low as 1 microM. The hydrolysis activity also was inhibited by
      SKF525, but less effectively. Eserine strongly inhibited the activity at 1 x 10(
      4) M. HgCl2 decreased the activity to about 40% at a concentration of 1 x 10(-4)
      M. FeCl3, CaCl2, MgCl2, and EDTA had little effect on the hydrolysis of
      eprinomectin, whereas NaF slightly increased the activity to 118%. Thus, the
      inhibition study suggested that eprinomectin deacetylase resembled "B" type
      carboxylesterase/amidases. The hydrolysis activity of eprinomectin and
      isocarboxazid, a specific substrate of RL2 [Hosokawa, M, Maki T and Satoh T
      (1987) Mol Pharmacol 31:579-584], by liver microsomes from rats treated with
      various cytochrome P-450 inducers correlated well (r = 0.92). Also, elusion
      profiles of esterase by gel filtration and ion exchange chromatography
      demonstrated that the active protein(s) for eprinomectin and isocarboxazid
      hydrolysis coeluted. Thus, RL2 or an enzyme system similar to RL2 is responsible
      for the N-deacetylation of eprinomectin.

PMID- 9929516
TI  - Development of an antipeptide antibody that binds to the C-terminal region of
      human CYP1B1.
AB  - An antipeptide antibody was raised against a 14-mer synthetic peptide
      (CDFRANPNEPA KMN) corresponding to the amino acid sequence from 491 to 504 of
      human cytochrome P-450 (CYP)1B1. Rabbit-derived antisera demonstrated the ability
      to induce moderately high antibody titers (>1:10(5)) as judged by enzyme-linked
      immunosorbent assay. In Western blot analysis, the purified antibody recognized a
      single protein band (estimated as 56 kDa) in microsomes prepared from human and
      rodent tissues. No significant cross-reactivity to either human CYP1A1 or human
      CYP1A2 protein was detected. Titration studies using recombinant human CYP1B1 and
      an enhanced chemiluminescence-based detection method demonstrated a minimal
      detection sensitivity for this antiserum at about 0.34 ng/band in 8 x 7-cm
      minigels. The immunoprecipitation and immunoinhibition results indicate that this
      antisera recognizes the nondenatured human CYP1B1 protein but does not inhibit
      its enzyme activity. Using this antibody, CYP1B1 protein was detected in nine
      different human tissues and in cultured cells induced by various chemicals. This
      highly specific, highly sensitive antibody provides an important tool to study
      tissue distribution and cellular expression levels of CYP1B1, with negligible
      cross-reactivity from the other members of the CYP1 family.

PMID- 9929517
TI  - Induction of cytochrome P-450 enzymes after repeated exposure to 4
      vinylcyclohexene in B6C3F1 mice.
AB  - 4-Vinylcyclohexene (VCH), an ovarian toxicant in mice, is known to irreversibly
      deplete ovarian follicles as a consequence of VCH diepoxide formation. Because
      ovotoxicity requires repeated dosing of VCH, the effect of consecutive daily
      doses of VCH (7.5 mmol/kg/day) on mouse liver microsomal activities and VCH
      epoxidation was determined. Cytochromes P-450 2B and 2A (CYP2B and CYP2A),
      principle isoforms involved in the bioactivation of VCH, as well as CYP2E1 and
      CYP3A were evaluated. VCH exposure increased total cytochrome P-450 content (35
      83% above control levels) after either 5, 10, or 15 days of treatment. Western
      blot analysis revealed an induction of CYP2A, CYP2B, and CYP2E1 at day 10.
      Elevated levels of CYP2A and CYP2B correlated with marker androstenedione and
      testosterone 16alpha- and 16beta-hydroxylase activities. Microsomes prepared from
      mice pretreated with VCH for 10 days demonstrated an increase (>/=2-fold) in the
      rate of VCH monoepoxide and diepoxide formation. Microsomal VCH epoxidation was
      increased to a similar extent by phenobarbital, acetone, and dexamethasone
      treatment. An increase in cytosolic glutathione S-transferase activity was
      observed after repeated VCH treatment, an enzyme potentially involved in
      detoxification of the VCH epoxides. Interestingly, preliminary studies indicated
      that circulating levels of the monoepoxide (vinylcyclohexene 1, 2-monoepoxide)
      and diepoxide of VCH were elevated after repeated dosing of VCH. Overall, the
      results indicate that repeated exposure of VCH in mice induces cytochrome P-450
      dependent activities, and in turn induction of its metabolism. Additional studies
      examining the toxicokinetics of VCH after repeated exposure are required to
      further delineate the relevance of induction in VCH-induced ovotoxicity.

PMID- 9929519
TI  - Role of the liver and gut in systemic diphenhydramine clearance in adult
      nonpregnant sheep.
AB  - We investigated the contribution of the liver and gut to systemic diphenhydramine
      (DPHM) clearance in adult nonpregnant sheep in two separate studies. In the first
      study, a simultaneous 50-mg bolus each of DPHM and its deuterium-labeled analog
      ([2H10]DPHM) was administered to five sheep via the femoral (i.v.) and the portal
      venous (p.v.) routes in a randomized manner. Arterial plasma concentrations of
      DPHM, [2H10]DPHM, and their deaminated metabolites, DPMA (diphenylmethoxyacetic
      acid) and [2H10]DPMA, were measured using gas chromatography-mass spectrometry.
      The hepatic first-pass extraction of DPHM after p.v. administration was 94.2 +/-
      3.7%. However, the area under the plasma concentration versus time profile of the
      metabolite after i.v. dosing was only 32.5 +/- 14.0% relative to that after p.v.
      administration. Thus, only approximately 32.5% of the i.v. dose is metabolized in
      the liver and a significant extrahepatic systemic clearance component is evident.
      Using the calculated total hepatic blood flow values, it was found that 98.6 +/-
      9.2% of the i.v. dose eventually was delivered to the "hepatoportal" system.
      Because the drug delivered to the hepatoportal system is almost completely
      eliminated in a single pass (hepatic extraction approximately 94%), this
      indicates a lack of any significant pulmonary drug uptake. Also, because only
      approximately 32.5% of the i.v. dose is metabolized in liver, the gut is most
      likely responsible for the clearance of the remainder. This gut contribution to
      systemic DPHM clearance was confirmed in a separate direct study in four sheep
      where the steady-state DPHM gut extraction ratio was 49.0 +/- 3.0%. Thus, gut
      accounts for a significant proportion (>/=50%) of DPHM systemic clearance in
      sheep in spite of a very high hepatic drug extraction efficiency.

PMID- 9929518
TI  - Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes.
AB  - The oxidative metabolism of irbesartan, a new nonpeptide angiotensin II receptor
      antagonist, was investigated on 12 human fully characterized hepatic microsomes
      and purified cytochrome P-450 (CYP) isoforms. After incubation of microsomes with
      irbesartan and NADPH, four main hydroxy metabolites were formed, as confirmed by
      liquid chromatography-mass spectrometry analysis. Irbesartan oxidation follows
      Michaelis-Menten kinetics, consistent with the involvement of a single CYP
      isoform in these hydroxylation processes. Only a low interindividual variability
      (2-fold difference) was observed in drug oxidation, even in preparations lacking
      CYP2D6. Km and Vmax for irbesartan oxidation were 54 +/- 6.5 microM and 0.62 +/-
      0.18 nmol/min/mg, respectively. Irbesartan oxidation correlated (r2 = 0. 769)
      with tolbutamide (CYP2C9 substrate) 4-methyl-hydroxylation. Oxidation of
      irbesartan was markedly inhibited by sulfaphenazole (CYP2C9 inhibitor), but not
      by any of several other CYP inhibitors. In the same manner, both tolbutamide and
      warfarin (CYP2C9 substrates), were competitive-type inhibitors of irbesartan
      oxidation with Ki values of 500 and 30 microM, respectively. Moreover, irbesartan
      was a competitive-type inhibitor of tolbutamide 4-methylhydroxylation (Ki = 317
      microM). Nifedipine also potentially decreased irbesartan oxidation, whereas
      neither ketoconazole and triacetyloleandomycin (CYP3A inhibitors), nor diltiazem
      and verapamil, (CYP3A4 substrates), exhibited an inhibitory effect. Additional
      studies demonstrated that nifedipine was an inhibitor of irbesartan (Ki = 20
      microM) and tolbutamide oxidation processes, whereas irbesartan had no effect at
      all on nifedipine dehydrogenation. Enzyme kinetics suggest that nifedipine is a
      noncompetitive-type inhibitor of CYP2C9-mediated catalytic activities. Finally,
      only microsomes containing recombinant human liver CYP2C9 were capable of
      oxidizing irbesartan. These results provide evidence that CYP2C9 plays a major
      role in irbesartan oxidation.

PMID- 9929520
TI  - Cytochrome P-450 isoforms involved in carboxylic acid ester cleavage of Hantzsch
      pyridine ester of pranidipine.
AB  - Cytochrome P-450 (CYP) isoforms responsible for the cleavage of Hantzsch pyridine
      ester at the 3-position of pranidipine were studied in vitro using cDNA-expressed
      human CYP enzymes. CYP1A1, 1A2, 2D6, and 3A4 cleaved the ester with a catalytic
      activity of 5.5, 0. 93, 13.1, and 22.4 nmol/30 min/nmol P-450, respectively.
      CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2E1 were not involved in the de-esterification.
      The Km and Vmax values for the de-esterification were 11.8 microM and 0.47
      nmol/min/nmol P-450 in the CYP2D6-catalyzed reaction and 8. 7 microM and 0.84
      nmol/min/nmol P-450 in the CYP3A4-catalyzed reaction. The intrinsic clearance
      (Vmax/Km) of the de-esterification by CYP3A4 was 2-fold greater than that by
      CYP2D6. Quinidine almost completely inhibited the CYP2D6-mediated de
      esterification at the concentration of 1 x 10(-6) M. Ketoconazole and
      troleandomycin inhibited the CYP3A4-mediated reaction in a dose-related manner.
      The results indicate that although the multiple CYP isoforms can catalyze the de
      esterification, CYP3A4 and 2D6 are the major isoforms.

PMID- 9929521
TI  - Identification of (-)-epicatechin metabolites and their metabolic fate in the
      rat.
AB  - After oral administration of (-)-epicatechin to rats, three kinds of metabolites
      (M-1, M-2, and M-3) were detected in the urine. After isolation of the compounds
      by preparative high-performance liquid chromatography, structural analysis was
      carried out by mass spectrometry and NMR. As a result, two compounds, M-1 and M
      2, were identified as (-)-epicatechin and 3'-O-methyl-(-)-epicatechin,
      respectively. M-3 was suggested to be a monomethylated (-)-epicatechin, but
      definitive elucidation was not possible because of its small quantity.
      Methylation of (-)-epicatechin with rat liver homogenates and subsequent
      structural analysis showed that M-3 was 4'-O-methyl-(-)-epicatechin.
      Identification of conjugated forms of the urinary metabolites also was attempted.
      Two conjugates in the urine were purified and analyzed by mass spectrometry and
      NMR. These conjugates were shown to be (-)-epicatechin-5-O-beta-glucuronide and
      3'-O-methyl-(-)-epicatechin-5-O-beta-glucuronide, respectively. Metabolism and
      excretion of (-)-epicatechin were examined. (-)-Epicatechin and its methylated
      derivatives in the free forms were detected in plasma and urine, but not in bile.
      Significant differences in the excretion ratio of the conjugated forms of (-)
      epicatechin and 3'-O-methyl-(-)-epicatechin were observed between urine and bile.
      Time-course analysis of (-)-epicatechin metabolites showed that the most
      predominant metabolites in plasma and urine were the conjugates of (-)
      epicatechin and 3'-O-methyl-(-)-epicatechin, respectively, and the cumulative
      amount of the urinary metabolites excreted during the 24-h period was about 8% of
      the administered (-)-epicatechin.

PMID- 9929522
TI  - Cocaine and tobacco use and the risk of spontaneous abortion.
AB  - BACKGROUND: Cigarette smoking and cocaine use may be risk factors for spontaneous
      abortion, but data supporting such a link are limited. METHODS: We studied the
      associations between cocaine and tobacco use and spontaneous abortion among
      pregnant adolescents and women (age range, 14 to 40 years) who sought care at an
      inner-city emergency department. A total of 400 adolescents and women had
      spontaneous abortions either at study entry or during follow-up (which lasted
      until 22 weeks' gestation), and 570 adolescents and women remained pregnant past
      22 weeks' gestation. Cocaine use was measured at base line by self-reports and
      analysis of urine and hair samples. Cigarette smoking was measured by self
      reports and urine analysis. RESULTS: The adolescents and women in both groups
      were predominantly black and of lower socioeconomic status. Among those who had
      spontaneous abortions, 28.9 percent used cocaine on the basis of hair analysis
      and 34.6 percent smoked on the basis of a urine cotinine assay, as compared with
      20.5 percent and 21.8 percent, respectively, of the adolescents and women who did
      not have spontaneous abortions. The presence of cocaine in hair samples was
      independently associated with an increase in the occurrence of spontaneous
      abortion (odds ratio, 1.4; 95 percent confidence interval, 1.0 to 2.1) after
      adjustment for demographic and drug-use variables. However, the use of cocaine as
      measured by self-reports and by urine analysis was not. The presence of cotinine
      in urine was also independently associated with an increased risk of spontaneous
      abortion (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.6). Twenty
      four percent of the risk of spontaneous abortion could be related to cocaine or
      tobacco use. CONCLUSIONS: Cocaine and tobacco use were common in our study
      population and were associated with a significant risk of spontaneous abortion.

PMID- 9929523
TI  - Improved detection of coronary artery disease by exercise electrocardiography
      with the use of right precordial leads.
AB  - BACKGROUND: Exercise electrocardiography is an perfect test for the detection of
      coronary artery disease. We attempted to improve the diagnostic accuracy of
      exercise testing as a noninvasive method for the detection of coronary artery
      disease by using a combination of the left and right precordial leads. METHODS:
      We studied 245 patients (218 men and 27 women) ranging from 32 to 74 years of age
      (mean [+/-SD], 52+/-8) who underwent treadmill exercise testing, thallium-201
      scintigraphy, and coronary arteriography. During exercise testing, each patient
      had one electrocardiogram recorded with the standard 12 leads and 3 right
      precordial leads (V3R, V4R, and V5R), with the results for each set of leads
      recorded and analyzed separately. RESULTS: On the basis of coronary
      arteriography, 34 patients had normal coronary arteries, 85 had single-vessel
      disease, 84 had two-vessel disease, and 42 had three-vessel disease. The
      sensitivities of the standard 12-lead exercise electrocardiogram, exercise
      electrocardiography incorporating right precordial leads, and thallium-201
      scintigraphy were 52 percent, 89 percent, and 87 percent, respectively, for the
      detection of single-vessel disease; 71 percent, 94 percent, and 96 percent for
      the detection of two-vessel disease; 83 percent, 95 percent, and 98 percent for
      the detection of three-vessel disease; and 66 percent, 92 percent, and 93 percent
      for the detection of any coronary artery disease. The specificities of the three
      methods for the detection of any coronary artery disease were 88 percent, 88
      percent, and 82 percent, respectively. CONCLUSIONS: Use of right precordial leads
      along with the standard six left precordial leads during exercise
      electrocardiography greatly improves the sensitivity of exercise testing for the
      diagnosis of coronary artery disease.

PMID- 9929524
TI  - Lack of effect of coumarin in women with lymphedema after treatment for breast
      cancer.
AB  - BACKGROUND: Lymphedema of the arms can be a serious consequence of local and
      regional therapy in women with breast cancer. Coumarin has been reported to be
      effective for the treatment of women with lymphedema; we undertook a study in
      which we attempted to replicate those findings. METHODS: We studied 140 women
      with chronic lymphedema of the ipsilateral arm after treatment for breast cancer.
      The women received 200 mg of oral coumarin or placebo twice daily for six months
      and then the other treatment for the following six months. The end points of the
      study consisted of the volume of the arm (calculated from measurements of hand
      and arm circumference) and the answers on a questionnaire completed by the
      patient about symptoms potentially related to lymphedema. RESULTS: The volumes of
      the arms at 6 and 12 months, were virtually identical, regardless of whether
      coumarin or placebo was given first. After six months, the average volume of the
      affected arm increased by 21 ml during placebo treatment and 58 ml during
      coumarin treatment (P=0.80). In addition, answers to patient-completed
      questionnaires were similar in the two treatment groups. After six months only 15
      percent of the women in the coumarin group and 10 percent of those in the placebo
      group reported that the study medication had helped a moderate or large amount
      (P=0.19). Coumarin was well tolerated, except that it resulted in serologic
      evidence of liver toxicity in 6 percent of the women. CONCLUSIONS: Coumarin is
      not effective therapy for women who have lymphedema of the arm after treatment
      for breast cancer.

PMID- 9929525
TI  - Risk of leukemia after platinum-based chemotherapy for ovarian cancer.
AB  - BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment
      for ovarian, testicular, and other cancers, but few investigations have
      quantified the late sequelae of such treatment. METHODS: We conducted a case
      control study of secondary leukemia in a population-based cohort of 28,971 women
      in North America and Europe who had received a diagnosis of invasive ovarian
      cancer between 1980 and 1993. Leukemia developed after the administration of
      platinum-based therapy in 96 women. These women were matched to 272 control
      patients. The type, cumulative dose, and duration of chemotherapy and the dose of
      radiation delivered to active bone marrow were compared in the two groups.
      RESULTS: Among the women who received platinum-based combination chemotherapy for
      ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence
      interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for
      treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6)
      and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found
      evidence of a dose-response relation, with relative risks reaching 7.6 at doses
      of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without
      chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia.
      CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of
      secondary leukemia. Nevertheless, the substantial benefit that platinum-based
      treatment offers patients with advanced disease outweighs the relatively small
      excess risk of leukemia.

PMID- 9929526
TI  - Images in clinical medicine. Mammographically occult breast cancer.

PMID- 9929527
TI  - The use of legal action in New York City to ensure treatment of tuberculosis.
AB  - BACKGROUND AND METHODS: After an increase in the number of cases of tuberculosis,
      New York City passed regulations to address the problem of nonadherence to
      treatment regimens. The commissioner of health can issue orders compelling a
      person to be examined for tuberculosis, to complete treatment, to receive
      treatment under direct observation, or to be detained for treatment. On the basis
      of a review of patients' records, we evaluated the use of these legal actions
      between April 1993 and April 1995. RESULTS: Among more than 8000 patients with
      tuberculosis, regulatory orders were issued for less than 4 percent. Among
      patients with a variety of social problems, only a minority required regulatory
      intervention: 10 percent of those with injection-drug use, 16 percent of those
      with alcohol abuse, 17 percent of those who were homeless, 29 percent of those
      who used "crack" cocaine, and 38 percent of those with a history of
      incarceration. A total of 150 patients were ordered to undergo directly observed
      therapy, 139 patients to be detained during therapy, 12 patients to be examined
      for tuberculosis, and 3 patients to complete treatment. These 304 patients had a
      median of three prior hospitalizations related to tuberculosis and one episode of
      leaving the hospital against medical advice. Repeatedly noncompliant patients and
      those who left the hospital against medical advice were more likely than others
      to be detained. The median length of detention was 3 weeks for infectious
      patients and 28 weeks for noninfectious patients. As compared with patients
      ordered to receive directly observed therapy, the patients who were detained
      remained infectious longer, had left hospitals against medical advice more often,
      and were less likely to accept directly observed therapy voluntarily. Altogether,
      excluding those who died or moved, 96 percent of the patients completed
      treatment, and 2 percent continued to receive treatment for multidrug-resistant
      tuberculosis. CONCLUSIONS: For most patients with tuberculosis, even those with
      severe social problems, completion of treatment can usually be achieved without
      regulatory intervention. Patients were detained on the basis of their history of
      tuberculosis, rather than on the basis of their social characteristics, and the
      less restrictive measure of mandatory directly observed therapy was often
      effective.

PMID- 9929528
TI  - Tuberculosis in patients with human immunodeficiency virus infection.

PMID- 9929529
TI  - Clinical problem-solving. A balancing act.

PMID- 9929530
TI  - Cocaine, smoking, and spontaneous abortion.

PMID- 9929531
TI  - The value of the right precordial leads of the electrocardiogram.

PMID- 9929532
TI  - The quality of life after breast cancer--solving the problem of lymphedema.

PMID- 9929533
TI  - Liberty and the control of tuberculosis.

PMID- 9929534
TI  - Corrections: Clonality of Reed-Sternberg Cells in Hodgkin's Disease.

PMID- 9929535
TI  - Corrections: Effect of Matching of Class I HLA Alleles on Clinical Outcome after
      Transplantation of Hematopoietic Stem Cells from an Unrelated Donor.

PMID- 9929536
TI  - The American health care system--Medicaid.

PMID- 9929537
TI  - Detection of accessory renal arteries with virtual vascular endoscopy of the
      aorta.
AB  - PURPOSE: To evaluate the diagnostic accuracy of virtual vascular endoscopy (VVE)
      in the detection of accessory renal arteries. METHODS: We retrospectively
      reviewed the CT angiography data sets of 67 patients (29 male and 38 female; age
      range 17-72 years, mean age 53 years) imaged for the study of the renal arteries,
      and affected by renovascular hypertension. All patients also had intraarterial
      digital subtraction angiography (DSA). CT angiography data sets were processed to
      obtain maximum intensity projection (MIP) and surface-rendered VVE of the aorta.
      Axial images, MIP, and VVE were evaluated separately and in combination in the
      detection of accessory renal arteries. Their results in terms of sensitivity and
      specificity were then compared with DSA. RESULTS: Axial images had a sensitivity
      of 88% and specificity of 94% for accessory renal artery detection, MIP had a
      sensitivity of 88% and specificity of 98%, and VVE had a sensitivity of 63% and a
      specificity of 88% (p < 0.05 vs DSA), but these increased to 88% and 98%
      respectively if endoscopic views were integrated with the other display
      techniques. CONCLUSION: VVE based on surface rendering does not add substantial
      benefits to CTY angiography; by contrast MIP is the most accurate display
      technique for the detection of accessory renal arteries.

PMID- 9929539
TI  - Covered stents in the treatment of peripheral arterial aneurysms: procedural
      results and midterm follow-up.
AB  - PURPOSE: To evaluate initial and midterm results of percutaneous treatment of
      peripheral aneurysms using covered stents. METHODS: Between June 1994 and
      December 1997 we used covered stents (EndoPro System or Passager) on 19 patients
      with peripheral aneurysms (7 iliac, 5 subclavian, 3 femoral, 3 popliteal, 1
      carotid). RESULTS: Successful aneurysm exclusion was achieved in 18 of 19
      patients (95%). In the short term (<30 days), one patient died of puncture site
      hemorrhage complicated by myocardial infarction; two femoral stents were
      surgically removed because of leakage. At subsequent follow-up (mean 20 months)
      two further unrelated deaths occurred. At 1 year (intention-to-treat) the stent
      was patent in 13 of 19 patients (68%) and the aneurysm was excluded in 17 of 19
      (89%). CONCLUSION: Treatment of peripheral aneurysms with covered stents has a
      high rate of immediate procedural success. Continued exclusion of the aneurysms
      is achieved in a large proportion of patients but there is a relatively high rate
      of stent thrombosis.

PMID- 9929538
TI  - Brain "embolism" detected by magnetic resonance imaging during percutaneous
      mitral balloon commissurotomy.
AB  - PURPOSE: The common finding of thrombi between the bifoil balloons when they were
      extracted after mitral dilation prompted us to look for evidence of minor brain
      embolisms using the sensitive technique of BMRI (brain magnetic resonance T2
      weighted imaging). METHODS: BMRI was performed within 48 hr before and after a
      percutaneous mitral balloon commissurotomy (PMBC) in each of the 63 patients in
      this study. RESULTS: There was evidence (hyperintensity foci: HI) of a previous
      asymptomatic brain embolism in 38 of 63 patients before PMBC and a new HI
      appeared in 18 of 63 patients after the procedure. New HI signals were found
      exclusively in the white matter in 8 of 18 patients and in only 3 of 18 were HI
      signs larger than 1 cm. One patient, with an HI signal >1 cm in the thalamus and
      another <1 cm in the brain stem, presented diplopia accompanied by other minor
      clinical signs. The differences in HI rate among four subgroups (1, older vs
      younger than 43 years; 2, sinus rhythm vs atrial fibrillation; 3, echo score <8
      vs >8; 4, patients from western countries vs the others) were not statistically
      significant, probably because the number of patients in each subgroup was low.
      Patients in atrial fibrillation had slightly more (not significant) HI before
      PMBC (15/20, 75%) than patients in sinus rhythm (23/43, 53%), but after PMBC
      their HI frequencies were similar (atrial fibrillation: 5/20, 25%; sinus rhythm:
      13/43, 30%). CONCLUSION: Brain microembolism is frequent during PMBC, but is
      often anatomically limited and free from clinical signs in most cases. Brain
      embolism seems to be related mainly to the procedure itself and not the features
      of the patient.

PMID- 9929540
TI  - Hepatic artery angiography and embolization for hemobilia following laparoscopic
      cholecystectomy.
AB  - PURPOSE: The effectiveness of angiography and embolization in diagnosis and
      treatment were assessed in a cohort of patients presenting with upper
      gastrointestinal hemorrhage secondary to hepatic artery pseudoaneurysm following
      laparoscopic cholecystectomy. METHODS: Over a 6-year period 1513 laparoscopic
      cholecystectomies were carried out in our region. Nine of these patients (0.6%)
      developed significant upper gastrointestinal bleeding, 5-43 days after surgery.
      All underwent emergency celiac and selective right hepatic artery angiography.
      All were treated by coil embolization of the right hepatic artery proximal and
      distal to the bleeding point. RESULTS: Pseudoaneurysms of the hepatic artery
      adjacent to cholecystectomy clips were demonstrated in all nine patients at
      selective right hepatic angiography. In three patients celiac axis angiography
      alone failed to demonstrate the pseudoaneurysm. Embolization controlled
      hemorrhage in all patients with no further bleeding and no further intervention.
      One patient developed a candidal liver abscess in the post-procedure period. All
      patients are alive and well at follow-up. CONCLUSION: Selective right hepatic
      angiography is vital in the diagnosis of upper gastrointestinal hemorrhage
      following laparoscopic cholecystectomy. Embolization offers the advantage of
      minimally invasive treatment in unstable patients, does not disrupt recent
      biliary reconstruction, allows distal as well as proximal control of the hepatic
      artery, and is an effective treatment for this potentially life-threatening
      complication.

PMID- 9929541
TI  - Percutaneous management of abscess and fistula following pancreaticoduodenectomy.
AB  - PURPOSE: To evaluate the efficacy of percutaneous drainage of fluid collections
      following pancreaticoduodenectomy (Whipple's procedure). METHODS: We performed a
      retrospective review of 19 patients referred to our service with fluid
      collections following pancreaticoduodenectomy. The presence of associated enteric
      or biliary fistulas, the route(s) of access for image-guided drainage, the
      incidence of positive bacterial cultures, and the duration and success of
      percutaneous management were recorded. RESULTS: Fistulous communication to the
      jejunum in the region of the pancreatico-jejunal anastomosis was demonstrable in
      all 19 patients by gentle contrast injection into drainage tubes. Three patients
      had concurrent biliary fistulas. In 18 of 19 patients, fluid samples yielded
      positive bacterial cultures. Successful percutaneous evacuation of fluid was
      achieved in 17 of 19 patients (89%). The mean duration of drainage was 31 days.
      CONCLUSION: Percutaneous drainage of abscess following pancreaticoduodenectomy is
      effective in virtually all patients despite the coexistence of enteric and
      biliary fistulas.

PMID- 9929542
TI  - Palliative treatment of malignant colorectal strictures with metallic stents.
AB  - PURPOSE: To assess the effectiveness and safety of self-expanding metallic stents
      as a primary palliative treatment for inoperable malignant colorectal strictures.
      METHODS: Under radiological guidance 20 self-expanding metallic Wallstents were
      implanted in 16 consecutive patients with colorectal stenoses caused by malignant
      neoplasms, when surgical treatment of the condition had been ruled out. The
      patients were followed up clinically for 1-44 months, until death or termination
      of this study. RESULTS: The stents were successfully implanted in all cases and
      resolved the clinical obstruction in all the patients except one, who underwent
      subsequent colostomy. During follow-up of the remaining 15 patients, clinical
      complications arising from the procedure were pain (two patients), minor rectal
      bleeding (one patient), and severe rectal bleeding (one patient) (26%). There
      were three cases of stent migration and three cases of stent occlusion, and
      reintervention by us was necessary in 20% of cases (3/15). The mean life span
      following the procedure was 130 days, and none of the patients exhibited clinical
      symptoms of obstruction at the time of death (12 patients) or termination of the
      study (3 patients). CONCLUSION: Deployment of metallic stents under radiologic
      guidance is an effective alternative as a primary palliative measure in malignant
      colorectal obstruction, though the possible clinical complications and need for
      repeat intervention during follow-up should be taken into account.

PMID- 9929543
TI  - First clinical experience with a high-capacity implantable infusion pump for
      continuous intravenous chemotherapy.
AB  - PURPOSE: To evaluate the efficiency of a new high-capacity pump for systemic
      venous chemotherapy and to verify the quality of implantation by interventional
      radiology staff. METHODS: A total of 47 infusion pumps with a 60-ml reservoir and
      variable flow rates (2, 6, 8, or 12 ml/24 hr) were implanted by radiologists in
      46 patients with solid tumor metastases requiring treatment with a single,
      continuously infused cytostatic agent. The reservoir was refilled
      transcutaneously, usually once weekly. The flow accuracy of the pump was assessed
      from actual drug delivery recorded on 34 patients over a minimum observation
      period of 180 days. RESULTS: No early complications occurred in any of the 47
      implants in 46 patients. A total of 12 (25.53%) complications occurred between 3
      and 24 months after implantation. Seven (14.90%) of these were due to the
      external design of the pump, while five (10.63%) were related to the central
      venous catheter. In the 34 patients available for pump evaluation (follow-up of
      at least 180 days), the system was used for a total of 14,191 days (range 180-911
      days, mean 417.38 days), giving an overall complication rate of 0.84 per 1000
      days of operation. The mean flow rate accuracy was 90.26%. CONCLUSION: The new
      implantable pump showed good flow rate accuracy and reliable operation. The pump
      related complications were related to its external design and have now been
      corrected by appropriate modifications. From a radiologic and surgical viewpoint,
      the venous implantation procedure is identical to that of conventional vascular
      access devices and can be performed by radiologists familiar with these
      techniques. The current limitations lie in the high cost of the pump and, for
      certain drugs, the short time between refills.

PMID- 9929544
TI  - Percutaneous introducibility of the expandable vascular sheath system and injury
      potential of balloon-assisted thrombectomy: preliminary In vivo results.
AB  - PURPOSE: To test the percutaneous introducibility of the expandable vascular
      sheath (EVS) system and the safety of percutaneous balloon-assisted thrombectomy.
      METHODS: The EVS was inserted directly (n = 9) or through a 9.5 Fr regular
      vascular introducer sheath (n = 9) into the femoral arteries and veins and
      carotid arteries in four dogs (18-21 kg). Balloon-assisted thrombectomies were
      simulated in iliac arteries. Histologic examinations were done at sites of funnel
      deployment immediately (n = 4) and 25 days (n = 8) after the intervention.
      RESULTS: The EVS was successfully introduced into six of nine vessels by a direct
      percutaneous approach. Balloon-assisted thrombectomy using the EVS device caused
      localized intimal denudation, disruption of the internal elastic lamina, and mild
      hemorrhages into the media; one arterial dissection at the site of funnel
      deployment was seen. All indirect insertions and funnel deployments were
      successful. Twenty-five days after the experiments, intimal hyperplasia was noted
      in all cases. CONCLUSION: Percutaneous balloon-assisted thrombectomy may cause
      mild vascular injuries. Direct percutaneous introduction of the EVS device cannot
      be recommended yet.

PMID- 9929545
TI  - Intravascular ultrasound and histology in in vitro assessment of iliac artery
      angioplasty.
AB  - PURPOSE: Intravascular ultrasound (IVUS) was used to assess in vitro the
      morphologic and quantitative effects of balloon angioplasty (PTA) of the iliac
      artery. METHODS: Forty human iliac arteries (>/= 30% area stenosis) were studied
      with IVUS in vitro before and after PTA and the findings were validated with
      histology. RESULTS: The sensitivity of IVUS for dissection was 74% and for media
      rupture 59%. The incidence of vascular damage was higher when the whole segment
      was analyzed rather than the target site alone. Dissections occurred at the
      thinnest region of the plaque, unrelated to plaque calcification. Following PTA,
      quantitative changes at the target site were greater compared with the overall
      data derived from all cross-sections. The increase in lumen area was caused
      solely by an increase in vessel area. CONCLUSIONS: IVUS is sensitive in detecting
      dissections, which occurred irrespective of calcification at the thinnest region
      of the plaque. The increase in lumen area after PTA was caused by stretching of
      the vessel.

PMID- 9929546
TI  - Differences in endothelial injury after balloon angioplasty, insertion of balloon
      expanded stents or release of self-expanding stents: An electron microscopic
      experimental study.
AB  - PURPOSE: To evaluate which of six different commonly available stents inserted
      into an artery without percutaneous transluminal angioplasty (PTA) causes the
      least endothelial damage. To compare the degree of endothelial injury after
      insertion of such a stent with injury caused by PTA. METHODS: Twelve healthy pigs
      were used in the experiments. In the first part of the study six different types
      of stents were inserted into the common iliac arteries. In the second part of the
      study self-expanding stents with large spaces between the wires were used. PTA
      was performed in the contralateral iliac artery. The pigs were killed immediately
      after the procedure and resected specimens examined after fixation, using
      scanning electron microscopy. RESULTS: All procedures but two were accomplished
      successfully. More endothelium was preserved after insertion of self-expanding
      stents with large spaces between the wires, compared with stents with small
      spaces and balloon-expanded stents. After insertion of self-expanding stents with
      large spaces, 50.1% +/- 16.4% of the endothelium remained intact, compared with
      only 5.6% +/- 7.7% after PTA. The difference was statistically significant (p <
      0.001). CONCLUSION: Self-expanding stents with large spaces between the wires,
      inserted without PTA, cause less damage to the endothelium than other stents and
      significantly less damage than PTA.

PMID- 9929547
TI  - Effects of contrast media on blood rheology: comparison in humans, pigs, and
      sheep.
AB  - PURPOSE: To compare whole blood viscosity and erythrocyte aggregation in humans,
      pigs, and sheep, before and after adding water-soluble iodinated contrast medium
      (CM). METHODS: Two CMs were studied: iopromide (nonionic) and ioxaglate (ionic).
      The blood-CM viscosity was measured with a Couette viscometer. Erythrocyte
      aggregation was measured with an erythroaggregometer. RESULTS: The blood-CM
      viscosity was increased up to +20% (relative to pure blood) with a CM
      concentration of 0%-10%. At CM concentrations from 10% to 50%, the viscosity
      decreased. The disaggregation shear stress was increased (relative to pure blood)
      at low CM concentration (0%-10%). When the CM concentration increased from 10% to
      20%, the disaggregation shear stress was decreased, except with the pig blood
      ioxaglate mixture. CONCLUSION: At low CM concentration the blood viscosity was
      increased in pig, sheep, and humans and the disaggregation shear stress was
      increased in pig and humans. The aggregation of sheep blood was too low to be
      detected by the erythroaggregometer. This rise can be explained by the formation
      of poorly deformable echinocytes. At higher CM concentration, the viscosity and
      the disaggregation shear stress decreased in relation to the blood dilution. We
      conclude that pig blood and sheep blood can both be used to study the effect of
      CM injection on blood viscosity. Nevertheless, the rheologic behavior of pig
      blood in terms of erythrocyte aggregation is closer to that of human blood than
      is sheep blood when mixed with CM. Pigs could thus be more suitable than sheep
      for in vivo studies of CM miscibility with blood during selective cannulation
      procedures.

PMID- 9929548
TI  - Treatment of a TIPS-biliary fistula by stent-graft in a 9-year-old boy.
AB  - We report a 9-year-old male cirrhotic patient with acute occlusion of a
      transjugular intrahepatic portosystemic shunt (TIPS) due to a biliary-to-TIPS
      fistula which occurred 9 hr after the TIPS procedure. Immediate TIPS revision was
      performed and the fistula was treated by placement of an endoluminal stent-graft.
      At 12-month follow-up color Doppler examination demonstrated a patent shunt.

PMID- 9929549
TI  - Focal enhanced areas of the liver on computed tomography in a patient with
      superior vena cava obstruction.
AB  - We present a patient with superior vena cava (SVC) obstruction in whom two areas
      of increased hepatic enhancement within the left lobe were seen on abdominal
      computed tomography (CT). The significance of this case is that abnormal
      enhancements of the liver on abdominal CT in the regions described should be
      suggestive of an SVC obstruction on this basis alone.

PMID- 9929550
TI  - Cross-sectional imaging in a case of adventitial cystic disease of the popliteal
      artery.
AB  - Adventitial cystic disease of the popliteal artery is an unusual condition of
      uncertain etiology, in which a mucin-containing cyst forms in the wall of the
      artery and produces lower extremity claudication, typically in young and middle
      aged men. A diagnosis of adventitial cystic disease of the popliteal artery was
      made preoperatively in a 47-year-old man by means of several imaging modalities,
      including angiography, magnetic resonance imaging, and ultrasound. The
      pathological findings confirmed the suggested diagnosis.

PMID- 9929551
TI  - Congenital absence of the internal carotid artery.
AB  - We report three cases of congenital absence of an internal carotid artery (ICA),
      diagnosed incidentally by digital subtraction angiography. The analysis of the
      cases is based on the classification of segmental ICA agenesis proposed by
      Lasjaunias and Berenstein. Usually the patients with this rare vascular anomaly
      are asymptomatic; some may have symptoms related to cerebrovascular
      insufficiency, compression by enlarged intracranial collateral vessels, or
      complications associated with cerebral aneurysms. Diagnosis of congenital absence
      of ICA is made by skull base computed tomography (CT) scan, CT and magnetic
      resonance angiography, and conventional or digital subtraction angiography.

PMID- 9929552
TI  - Percutaneous retrieval of a central venous catheter sutured to the wall of the
      right atrium.
AB  - A transjugular central venous catheter was inadvertently sutured to the wall of
      the right atrium in a 63-year-old female during coronary bypass surgery. Using
      two nitinol Goose Neck snares via a transfemoral and a transjugular approach the
      catheter was severed into two pieces and retrieved percutaneously.

PMID- 9929553
TI  - Computed tomography-guided central venous catheter placement in a patient with
      superior vena cava and inferior vena cava occlusion.
AB  - An 18-year-old man with a gastrointestinal hypomotility syndrome required
      lifelong parenteral nutrition. Both the superior and inferior vena cava were
      occluded. Computed tomography guidance was used to place a long-term central
      venous catheter via a large tributary to the azygos vein.

PMID- 9929554
TI  - Re: duplicated IVC with normal-appearing right IVC and azygos continuation of the
      left IVC.

PMID- 9929555
TI  - Re: left portal vein as a direct source of gastric varices.

PMID- 9929556
TI  - Evidence for a Na+/Ca2+ exchange mechanism in frog skin epithelium.
AB  - In the present study we investigated the possible existence of a Na+/Ca2+
      exchange mechanism in the basolateral membrane of the frog skin epithelium and
      whether such a mechanism plays a role in the regulation of transepithelial Na+
      transport. Cytosolic calcium ([Ca2+]i) was measured with the probe fura-2 in a
      set-up in which pieces of tissue were mounted on the stage of an epifluorescence
      microscope. Na+ transport was measured as the amiloride-sensitive short-circuit
      current (Isc) using a conventional voltage clamp. Basal [Ca2+]i was 65+/-6 nM
      (n=15). Removal of Na+ from the mucosal solution had no effect on [Ca2+]i. When
      Na+ was removed from the serosal solution, [Ca2+]i increased biphasically to a
      peak of 220+/-38 nM (n=8, P=0.006). Readdition of Na+ to the serosal solution
      returned [Ca2+]i to control level. The serosal Na+ gradient and changes in
      [Ca2+]i were closely correlated; stepwise changes in serosal Na+ were followed by
      stepwise changes in [Ca2+]i. These observations indicate the existence of a
      Na+/Ca2+ exchange mechanism in the basolateral membrane of the frog skin
      epithelium. The transepithelial Na+ transport decreased from 13.2+/-1.8 to 9.2+/
      1.5 microA cm-2 (n=8, P=0.049) when Na+ was omitted from the serosal solution.
      When this protocol was repeated in the absence of serosal Ca2+, Na+ transport
      decreased similarly from 16.7+/-1.7 to 11.6 +/-1. 8 microA cm-2 (n=6, P=0.004).
      We conclude that it is unlikely that the observed decrease in Isc after removal
      of serosal Na+ is due to an increase in [Ca2+]i per se.

PMID- 9929557
TI  - An improved isolated, left ventricular ejecting, murine heart model. Functional
      and metabolic evaluation.
AB  - An improved, isolated, left ventricular-ejecting, murine heart model is described
      and evaluated. Special attention was paid to the design and impedance
      characteristics of the artificial aortic outflow tract and perfusate composition,
      which contained glucose (10 mM plus insulin) and pyruvate (1.5 mM) as substrates.
      Temperature of the isolated perfused hearts was maintained at 38.5 degrees C.
      During antegrade perfusion (preload 10 mm Hg, afterload 50 mm Hg, 2.5 mM Ca2+)
      proper design of the aortic outflow tract provided baseline values for cardiac
      output (CO), left ventricular developed pressure (LVDP) and the maximum first
      derivative of left ventricular pressure (LV dP/dtmax) of 11.1+/-1.7 ml min-1,
      83+/-5 mm Hg and 6283+/-552 mm Hg s-1, respectively, resembling findings in the
      intact mouse. During 100 min normoxic antegrade perfusion CO declined non
      significantly by less than 10%. Varying pre- and afterloads resulted in typical
      Frank-Starling relationships with maximal CO values of 18.6+/-1.8 ml min-1 at pre
      and afterload pressures of 25 and 50 mm Hg, respectively. Left ventricular
      function curves were constructed at free [Ca2+] of 1.5 and 2.5 mM in the
      perfusion medium. Significantly higher values for CO, LVDP and LV dP/dtmax and LV
      dP/dtmin were obtained at 2.5 mM Ca2+ at all loading conditions investigated.
      Phosphocreatine and creatine levels remained stable throughout the perfusion
      period. Despite a small but significant decline in tissue ATP content, the sum of
      adenine nucleotides did not change during the normoxic perfusion period. The
      tissue content of glycogen increased significantly.

PMID- 9929558
TI  - Expression of early hippocampal CA1 LTP does not lead to changes in AMPA-EPSC
      kinetics or sensitivity to cyclothiazide.
AB  - We have analysed whether the expression of long-term potentiation (LTP) in rat
      hippocampal CA1 neurons involves a change in the kinetics of (S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory
      postsynaptic currents (EPSCs) (AMPA-EPSCs) or their susceptibility to the AMPA
      receptor modulator cyclothiazide. AMPA-EPSCs in the CA1 region were evoked by
      alternate stimulation of two independent Schaffer collateral-commissural inputs
      of slices of adult rat hippocampus. In the current-clamp mode a strong tetanus
      (100 Hz, 1 s) applied to one input (input I) induced stable LTP of AMPA-EPSCs in
      this input, while the control input (input II) remained unaffected. For neither
      input were EPSC rise time and decay kinetics significantly changed. The
      application of cyclothiazide prolonged the rise time and the decay time constants
      of the AMPA-EPSCs in both control and potentiated inputs to the same extent
      (Input I-rise time: 198+/-8%, decay: 148+/-12%; input II-rise time: 212+/-14%,
      decay: 144+/-19%; n=8). Furthermore, when present during tetanization
      cyclothiazide did not occlude LTP, suggesting that cyclothiazide and tetanic
      stimulation enhance AMPA-EPSCs via independent mechanisms. Our findings argue
      against changes in (de-)activation or desensitization of AMPA receptors as the
      molecular basis for the expression of LTP.

PMID- 9929559
TI  - Effects of external cadmium ions on excitation-contraction coupling in rat soleus
      fibres.
AB  - The actions of external Cd2+ on the twitch and tetanic contractions, action
      potentials and potassium (K+) contractures of rat soleus muscle fibre bundles
      have been investigated. Cd2+ at 1-1.5 mM did not significantly alter tetanic
      tension, but increased twitch tension and increased the duration and overshoot of
      action potentials. At >/=3 mM, Cd2+ (1) depressed tetanic contractions and
      initially potentiated but later depressed twitches, (2) abolished the action
      potential overshoot, and (3) shifted peak K+ contracture tension to more positive
      membrane potentials. Twitch and tetanic contractions, and action potentials
      remained depressed when Cd2+ was washed out of the bath. The effects of Cd2+ on
      the twitch, tetanus and action potential were mimicked by Zn2+, while La3+ and
      Co2+ at 3 mM - or Mg2+ and Ca2+ at 30 mM - depressed peak twitch and tetanic
      tension, but did not potentiate twitches. The results suggest that: (1) Cd2+ and
      Zn2+ potentiate twitch tension by prolonging action potential depolarisation; (2)
      Cd2+ depresses twitch and tetanic tension by reducing the action potential
      overshoot, and causing a positive shift in the voltage dependence of contraction;
      and (3) the irreversible depression of action potential amplitude in rat soleus
      muscle is a specific property of Cd2+ and Zn2+ that is not shared by Co2+, Mg2+
      or Ca2+.

PMID- 9929560
TI  - A diazo-2 study of relaxation mechanisms in frog and barnacle muscle fibres:
      effects of pH, MgADP, and inorganic phosphate.
AB  - The aim of this study was to compare the effects of increased concentrations of
      MgADP, inorganic phosphate (Pi) and H+ ([MgADP], [Pi] and [H+], respectively) on
      the rate of relaxation in two different muscle types: skinned muscle fibres from
      the frog Rana temporaria and myofibrillar bundles from the giant Pacific acorn
      barnacle Balanus nubilus. Relaxation transients are produced by the photolysis of
      diazo-2 and are well fitted with a double exponential curve, giving two rate
      constants: k1 [5.6+/-0.1 s-1 for barnacle, n=30; 26.3+/-0.7 s-1 for frog, n=14
      (mean+/-SEM)] and k2 [0.6+/-0.1 s-1 in barnacle, n=30; 10.4+/-1.0 s-1 in frog,
      n=14 (mean+/-SEM)], at 10 degrees C. Decreasing the pH by 0.5 pH units did not
      significantly affect k1 for barnacle relaxation [5.6+/-0.1 s-1 (mean+/-SEM),
      n=15] compared to the decrease in k1 of 40% seen in frog. Use of the Ca2+
      sensitive fluorescent label acrylodan on barnacle wild-type troponin C
      demonstrated that decreasing the pH from 7.0 to 6.6 only alters the pCa50 value
      by 0.23 in the cuvette, while stopped-flow experiments with acrylodan revealed no
      significant change in koff from the labelled protein [322+/-32 s-1 at pH 7.0 and
      381+/-24 s-1 (mean+/-SEM) at pH 6.6]. Increasing [MgADP] by 20 microM (50 microM
      added ADP) from control values of 50 microM in frog decreased k1 to 12.3+/-0.4 s
      1 (mean+/-SEM, n=8), and at 400 microM MgADP, k1=9.6+/-0.1 s-1 (mean+/-SEM,
      n=12). In barnacle, 500 microM MgADP had a much smaller effect on k1 (4.0+/-0. 9
      s-1, mean+/-SEM, n=8). Increasing the free [Pi] from the contaminant level of
      0.36 mM to 1.9 mM slowed k1 by approximately 15% in barnacle [4.8+/-0.8 s-1,
      mean+/-SEM, n=7], compared to a approximately 30% reduction seen in frog. We
      conclude that the differences between barnacle and frog seen here are most
      probably due to different isomers of the contractile proteins, and that events
      underlying the crossbridge cycle are the same or similar. We interpret our
      results according to a model of crossbridge transitions during relaxation.

PMID- 9929562
TI  - AVP-induced mitogenic responses of Chinese hamster ovary cells expressing human
      V1A or V1B receptors.
AB  - Arginine vasopressin (AVP) induces cell proliferation and hypertrophy; however,
      the human receptor subtype and the intracellular signaling pathways responsible
      for this mitogenic activity remain unclear. Experiments were conducted to
      determine which AVP receptor is linked to mitogen-activated protein (MAP) kinase
      activation and the mitogenic effect seen in Chinese hamster ovary (CHO) cells
      expressing human V1A or V1B receptors. Adding AVP to CHO cells transfected with
      human V1A or V1B cDNA significantly and concentration-dependently induced
      activation of MAP kinase and increased DNA synthesis, as measured by
      [3H]thymidine incorporation. These effects were inhibited by AVP receptor
      antagonists and the potency order of antagonists in vitro was similar to that
      observed in radioligand binding assays. These results suggest that AVP induces
      the MAP kinase cascade leading to cell proliferation through either human V1A or
      V1B receptors, and that these cloned, expressed AVP receptors may prove an
      invaluable tool for probing the physiologic and pathophysiologic effects of AVP.

PMID- 9929563
TI  - Protein kinase C stimulates swelling-induced chloride current in canine atrial
      cells.
AB  - The whole-cell patch-clamp technique was used to study the effect of protein
      kinase C (PKC) stimulation and alpha-adrenergic agonists on the swelling-induced
      chloride current (ICl,swell) in canine atrial cells. ICl,swell was activated by
      positive-pressure inflation. 4beta-Phorbol 12, 13-dibutyrate (PDBu) concentration
      dependently stimulated ICl,swell. PDBu (500 nM) increased the current density of
      ICl,swell from 9.1+/-1.3 to 24.2+/-4.8 pA/pF at +20 mV (n=4). This effect
      developed slowly, reaching a steady-state after more than 5 min of exposure.
      4alpha-Phorbol 12, 13-dibutyrate (4alpha-PDBu, 500 nM), an inactive analogue of
      PDBu, did not affect ICl,swell. The effect of PDBu was inhibited by
      bisindolylmaleimide I. After down regulation of PKC by phorbol 12-myristate 13
      acetate (PMA, 1.6 microM, 24 h), ICl,swell no longer responded to PDBu (n=4).
      Neither the basal whole-cell current (prior to cell inflation) nor inflation
      induced ICl,swell were affected by PKC down regulation. Phenylephrine did not
      affect ICl,swell. We conclude that PKC activity stimulates and does not prevent
      the activation of dog atrial ICl,swell. These results contrast with reports of
      PKC-dependent inhibition of rabbit atrial ICl,swell and currents conducted by ClC
      3, a putative clone for ICl,swell. The data suggest species-dependent variations
      in the modulation of cardiac ICl,swell by PKC.

PMID- 9929561
TI  - EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog
      skin epithelium.
AB  - We examined the effect of prostaglandin E2 (PGE2) on antidiuretic hormone (ADH)
      dependent Na+ transport and cAMP production in isolated frog skin epithelium. ADH
      caused an increase in transepithelial Na+ transport and a decrease in cellular
      potential, indicating an increase in apical Na+ permeability. Subsequent addition
      of PGE2 decreased Na+ transport and repolarised the cells. The PGE2 receptor
      EP1/3-selective analogue sulprostone and the PGE2 receptor EP2/3-selective
      analogue misoprostol were able to mimic the effect of PGE2. ADH increased
      cellular cAMP levels, whereas PGE2, sulprostone and misoprostol were able to
      reduce the ADH-dependent cAMP production. Measurements of intracellular Ca2+
      concentration ([Ca2+]i) revealed that it was unaffected by both PGE2 and
      sulprostone. The inhibitory effect of PGE2 on ADH-dependent Na+ transport was
      also observed in Ca2+-depleted epithelia. We conclude that ADH stimulates
      transepithelial Na+ transport by increasing cellular cAMP levels, whereas PGE2
      inhibits ADH-dependent Na+ transport by activating EP3-type receptors, which
      decrease cellular cAMP levels. We have found no evidence that [Ca2+]i is involved
      in the regulation of ADH-dependent Na+ transport by PGE2.

PMID- 9929564
TI  - Insulin modulation of ATP-sensitive K+ channel of rat skeletal muscle is impaired
      in the hypokalaemic state.
AB  - In the present work, we examined the effects of in vivo administration of insulin
      to rats made hypokalaemic by feeding a K+-free diet. The i.p. injection of
      insulin in the hypokalaemic rats provoked muscle paralysis within 3-5 h.
      Consistent with this observation, the skeletal muscle fibres of the paralysed
      rats were depolarized. In contrast, in the normokalaemic animals, insulin neither
      provoked paralysis nor produced significant fibre hyperpolarization. In the
      hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine
      triphosphate (ATP)-sensitive K+ currents without altering the sensitivity of the
      channels to ATP or glibenclamide. In contrast, in the normokalaemic rats, insulin
      enhanced ATP-sensitive K+ currents that became also resistant to ATP and
      glibenclamide. Our experiments indicate that the modulation of the sarcolemma ATP
      sensitive K+ channels by insulin is impaired in the hypokalaemic state. This
      phenomenon appears to be related to the fibre depolarization and paralysis
      observed in the same animals.

PMID- 9929565
TI  - Ca2+ channel inhibition induced by nitric oxide in rat insulinoma RINm5F cells.
AB  - The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in
      insulin-secreting RINm5F cells was investigated using the patch-clamp technique
      in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced
      a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The
      IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N
      acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current
      amplitude. When 200 microM SNP was administered together with the NO scavenger 2
      (4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO,
      300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500
      microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP)
      mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current
      amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2,
      4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM
      SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of
      controls after the blockade of L-type Ca2+ channels and 30% in the presence of
      2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L
      type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the
      intracellular levels of cGMP. NO may then significantly influence the Ca2+
      dependent release of hormones from secretory cells as well as that of
      neurotransmitters from nerve terminals.

PMID- 9929566
TI  - Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and
      Na+/Cl-/betaine transporter mRNAs in individual cells of the kidney during
      changes in the diuretic state.
AB  - The effect of changes in medullary extracellular tonicity on mRNA expression for
      aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and
      Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using
      Northern blot analysis and non-radioactive in situ hybridization in four groups
      of rats: controls, acute diuresis (the loop diuretic furosemide was
      administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of
      diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute
      administration of the loop diuretic furosemide significantly reduced AR, SMIT and
      BGT gene expression in the inner and outer medulla compared with controls.
      Administration of dDAVP to chronically diuretic rats raised the expression of
      these three mRNAs in the inner but not the outer medulla compared with the
      chronically diuretic rats. None of these alterations in medullary tonicity
      significantly changed SDH expression. The in situ hybridization studies showed
      AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial
      cells of the outer and inner medulla. The various cell types (epithelial,
      endothelial and interstitial cells) differed in their expression pattern and
      intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded
      uniformly to a decrease in extracellular tonicity with a reduction, and to an
      increase with enhancement of their AR, BGT and SMIT expression.

PMID- 9929567
TI  - Blood flow to the brown adipose tissue of conscious young rabbits during hypoxia
      in cold and warm conditions.
AB  - Brown adipose tissue (BAT) non-shivering thermogenesis is stimulated by cold
      temperature and depressed by hypoxia. We investigated the extent to which changes
      in metabolic rate during cold and hypoxia, singly or combined, were accompanied
      by changes in BAT perfusion. One-month-old rabbits were instrumented for
      measurements of regional blood flow by the coloured microsphere technique. One
      group of rabbits was tested in warm (24 degrees C, n=17), and the other in cold
      (13 degrees C, n=9) conditions, first in normoxia (inspired oxygen concentration
      FIO2 about 21%, arterial oxygen saturation SaO2 approximately 88%) followed by
      hypoxia (FIO2 approximately 10%, SaO2 approximately 54%). In warm conditions,
      oxygen consumption (VO2, measured by an open-flow method) averaged 22 ml.kg-1.min
      1 (STPD), and BAT blood flow 98 ml.100g-1.min-1. In hypoxia, VO2 dropped on
      average to 87%, whereas BAT flow dropped to 43% of the normoxic values. In the
      cold during normoxia, VO2 averaged 31 ml.kg-1.min-1 (STPD), and BAT blood flow
      was 155 ml.100g-1.min-1. In cold and hypoxia VO2 dropped to 19 ml.kg-1.min-1
      (STPD) (i.e. 60% of the normoxic value), whereas BAT blood flow was not altered
      significantly (148 ml.100g-1.min-1). Hence, BAT blood flow decreased in hypoxia
      in absence of cold stimuli, whereas it remained high when hypoxia occurred during
      cold, despite the major drop in VO2. We conclude that cold is more important than
      hypoxia in determining BAT perfusion, and that changes in BAT blood flow are not
      a mechanism for the hypoxic control of V.O2.

PMID- 9929568
TI  - The activity-dependent potentiation of the slow Ca2+-activated K+ current
      regulates synaptic efficacy in rat CA1 pyramidal neurons.
AB  - Activity-dependent modifications of neuronal excitability are of key functional
      importance because they accomplish general postsynaptic control of the flow of
      synaptic signals. We tested the modifications of synaptic efficacy evoked in rat
      CA1 hippocampal pyramidal neurons during the short-term activity-dependent
      reduction in excitability termed "response depression". The in vitro slice
      technique and recordings with sharp electrodes in the current- and voltage-clamp
      modes were used. Depression was induced by repeatedly stimulating the Schaffer
      collateral and stratum oriens. Repeated synaptic stimuli also depressed
      subsequent responses evoked by transmembrane current pulse injection and vice
      versa. Depression was characterised by a marked decrease in synaptic efficacy
      that outlasted stimuli for several minutes and was generalized to all pyramidal
      cells. The action potential frequency adaptation, the slow after
      hyperpolarization and the underlying slow Ca2+-dependent K+ current (IAHP) were
      potentiated during depression. The potentiated IAHP caused depression by acting
      as a cumulative negative feedback that reduced synaptic efficacy by increasing
      the membrane conductance and hyperpolarizing the neurone. This depression may act
      as a homeostatic negative feedback mechanism to limit the rise in intracellular
      Ca2+ concentration and stabilize the membrane potential following intense
      synaptic activation.

PMID- 9929569
TI  - Control of shortening speed in single guinea-pig taenia coli smooth muscle cells
      by Ca2+, phosphorylation and caldesmon.
AB  - We studied the effect of caldesmon peptides on the regulation of shortening of
      single guinea-pig taenia coli cells permeabilised with saponin. When contraction
      was initiated by Ca2+ and MgATP shortening rate at pCa 4.5 was 0.17+/-0.04 cell
      lengths s-1 and half-maximal rate was at pCa 5.6. Following thiophosphorylation
      with 1 mM adenosine 5'-O-(3-thiotriphosphate) (ATP[gamma-S]) at pCa 4.5 for 10
      min, on addition of ATP these cells contracted at of 0.25+/-0.04 cell lengths s-1
      independently of pCa. If thiophosphorylated cells were preincubated with H1
      (domains 3 and 4 of caldesmon), shortening speed was reduced (ID50=2 microM).
      Shortening speed was also reduced by 658C (domain 4b) at higher concentrations
      (ID50=400 microM). H13 (domain 4a), which does not block weak binding but
      inhibits actin-tropomyosin, inhibited cell shortening (ID50=6 microM). H2, which
      blocks weak binding but does not inhibit actin-tropomyosin, did not inhibit
      shortening. Western blots of the cells showed that the peptides were tightly
      bound within the cell but the native caldesmon was not displaced. These results
      indicate that exogenous caldesmon peptides added to smooth muscle cells may be
      incorporated into the thin filaments and produce effects on shortening, as
      expected if it were involved in tropomyosin-dependent inhibition of the actin
      filament in the cell.

PMID- 9929570
TI  - Spontaneous Na+ and Ca2+ spike firing of cerebellar Purkinje neurons at high
      pressure.
AB  - The effects of high pressure (up to 10.1 MPa) on the spontaneous firing of
      Purkinje neurons in guinea-pig cerebellar slices were studied using the
      macropatch clamp technique. Pressure did not significantly alter the single
      somatic Na+ spike parameters or the frequency of regular Na+ spike firing. When
      Na+ currents were blocked by 0.5-1 microM tetrodotoxin (TTX), a pressure of 10.1
      MPa slightly reduced the dendritic Ca2+ spike amplitude to 90.2+/-3.1% of its
      control value, and slowed its kinetics. The effects of pressure on the single
      Ca2+ spike were even less prominent when K+ currents were blocked by 5 mM 4
      aminopyridine (4-AP). Pressure prolonged the active period of Ca2+ spike firing
      to 152.2+/-10.4% of the control value. Within the active period pressure
      increased the inter-spike interval to 164.9+/-8.7% and suppressed the typical
      firing of doublets. The latter changes were reversed by a high extracellular
      potassium concentration ([K+]o) and 1 microM 4-AP, whereas in the presence of 5
      mM 4-AP the pattern was insensitive to pressure. A high [Ca2+]o reduced the
      firing frequency and suppressed doublet firing in a manner reminiscent of the
      pressure effect, but these changes could not be reversed by 4-AP. A low [Ca2+]o
      slightly increased the firing of doublets. These results show that the single
      somatic Na+ spike is insensitive and the dendritic Ca2+ spike is only mildly
      sensitive to pressure. However, alterations in Ca2+ spike firing pattern suggest
      that modulation of dendritic K+ currents induce depression of dendritic
      excitability at pressure.

PMID- 9929571
TI  - An automatic temperature-control system for solutions in free flow.
AB  - We describe a temperature-control system for solutions in free flow, suitable for
      electrophysiological or optical studies of isolated cells, natural epithelia or
      cell culture monolayers. The system is small enough to be located close to the
      preparation and was designed specifically to be coupled to the inlets of a
      modified, continuous-flow Ussing chamber, allowing rapid change of the solutions
      bathing tissue surfaces. The system consists of a highly compact monoblock
      heating unit and a control circuit. Solutions from different reservoirs, kept at
      room temperature or lower (from an ice bath), can be rapidly switched at the
      inlet of the heating unit by manually or electrically actuated microvalves
      without affecting the temperature of the fluid leaving the heating unit. The
      control unit consists of a bead thermistor firmly placed close to the heating
      unit outlet and an electronic circuit which is basically a proportional
      controller. This unit continuously regulates the electric current through the Ni
      Cr heater, keeping the temperature of the fluid leaving the heating unit constant
      at a preset value. The system allows control of fluid temperature (normally 37
      degrees C) for flow rates in the range of 1.0 ml/min to 12 ml/min. However, the
      temperature can be set at any value above that of the incoming fluid.

PMID- 9929572
TI  - On the mechanism of GABA-induced currents in cultured rat cortical neurons.
AB  - We applied the perforated-patch-clamp technique to cultured cortical neurons of
      the rat to characterize the ionic basis of membrane potential changes and
      membrane currents induced by gamma-aminobutyric acid (GABA). Gramicidin was used
      as the membrane-perforating agent, to allow the recording of whole-cell currents
      without impairing the intracellular Cl- concentration ([Cl-]i). In current-clamp
      experiments in the presence of 26 mM HCO3- the application of 50 microM GABA
      evoked changes in the membrane potential of neurons including depolarizations
      (19%), hyperpolarizations (38%) and biphasic changes in membrane potential (31%),
      characterized by a transient hyperpolarization followed by a sustained
      depolarization. Accordingly, GABA (50-200 microM) induced inward, outward or
      biphasic current responses under voltage-clamp. Inward and biphasic currents as
      well as depolarizations and biphasic membrane potential responses, respectively,
      occurred more frequently in the presence of 26 mM HCO3-. The second phase of the
      biphasic membrane potential or current responses was markedly reduced when the
      preparation was bathed in a HCO3--free saline, indicating a contribution from
      HCO3-. The reversal potential of the GABA-induced currents (EGABA) determined
      with the gramicidin-perforated-patch mode and in the nominal absence of HCO3- was
      -73 mV, while it was shifted to -59 mV in the presence of HCO3-. Combined patch
      clamp and microfluorimetric measurements using the Cl--sensitive dye 6-methoxy-1
      (3-sulphonatopropyl)quinolinium (SPQ) showed that GABA evoked an increase of [Cl
      ]i in 54% (n=13) of the neurons. We conclude that this increase of [Cl-]i in
      combination with the efflux of HCO3- results in a shift of EGABA above the
      resting membrane potential that gives rise to GABA-mediated depolarizations.

PMID- 9929573
TI  - Molecular and functional characterization of s-KCNQ1 potassium channel from
      rectal gland of Squalus acanthias.
AB  - Functional and pharmacological data point to the involvement of KCNQ1/IsK
      potassium channels in the basolateral potassium conductance of secretory
      epithelia. In this study, we report the cloning and electrophysiological
      characterization of the KCNQ1 protein from the salt secretory rectal gland of the
      spiny dogfish (Squalus acanthias). The S. acanthias KCNQ1 (s-KCNQ1) cDNA was
      cloned by polymerase chain reaction (PCR) intensive techniques and showed overall
      sequence similarities with the KCNQ1 potassium channel subunits of Man, mouse and
      Xenopus laevis of 64, 70 and 77%, respectively, at the translated amino acid
      level. Analysis of s-KCNQ1 expression on a Northern blot containing RNA from
      heart, rectal gland, kidney, brain, intestine, testis, liver and gills revealed
      distinct expression of 7.4-kb s-KCNQ1 transcripts only in rectal gland and heart.
      Voltage-clamp analysis of s-KCNQ1 expressed in Xenopus oocytes showed pronounced
      electrophysiological similarities to human and murine KCNQ1 isoforms, with a
      comparable sensitivity to inhibition by the chromanol 293B. Coexpression of s
      KCNQ1 with human-IsK (h-IsK) induced currents with faster activation kinetics and
      stronger rectification than observed after coexpression of human KCNQ1 with h
      IsK, with the voltage threshold of activation shifted to more negative
      potentials. The low activation threshold at approximately -60 mV in combination
      with the high expression in rectal gland cells make s-KCNQ1 a potential candidate
      responsible for the basolateral potassium conductance.

PMID- 9929574
TI  - Miniature Ca2+ channels in excised plasma-membrane patches: activation by IP3.
AB  - In the present work, we characterized the receptor properties and the conductive
      features of the inositol (1,4,5)-trisphosphate (IP3)-activated Ca2+ channels
      present in excised plasma-membrane patches obtained from mouse macrophages and
      A431 cells. We found that the receptor properties of the channels tested were
      similar to those of the IP3 receptor (IP3R) expressed in the endoplasmic
      reticulum (ER) membrane. These properties include activation by IP3, inhibition
      by heparin, time-dependent inactivation by high IP3 concentrations, activation by
      guanosine 5'o-thiotriphosphate and regulation by arachidonic acid. On the other
      hand, in terms of conductive properties, the channel closely resembles Ca2+
      release-activated Ca2+ channels (Icrac). These conductive properties include
      extremely low conductance (approximately 1 pS), very high selectivity for Ca2+
      over K+ (PCa/PK>1000), inactivation by high intracellular Ca2+ concentration and,
      importantly, strong inward rectification. Notably, the same channel was activated
      by: (1) agonists in the cell-attached mode of channel recording, and (2)
      cytosolic IP3 after patch excision. Although the possibility cannot be completely
      excluded that a novel type of IP3R is expressed exclusively in the plasma
      membrane, in their entirety our findings suggest that the plasma membrane of
      mouse macrophages and A431 cells contains Icrac-like Ca2+ channels coupled to an
      IP3-responsive protein which displays properties similar to those of the IP3R
      expressed in the ER membrane.

PMID- 9929576
TI  - [Dermatomycosis in human and animals].
AB  - Dermatomycosis including dermatophytosis, sporotrichosis and cryptococcosis
      commonly occurs in humans and animals all and are considered to be zoonotic
      diseases. Recently, human cases of dermatophytosis transmitted from animals are
      increasing in number due to changes in the environments of human and animal life.
      Three species of dermatophytes, Microsporum canis, Trichophyton mentagrophytes
      and T. verrucosum are the most important pathogens from animal to human,
      respectively. Therefore, it is necessary to understand their biological and
      ecological characteristics to correctly diagnose and treat the disease. Some
      human cases of sporotrichosis and cryptococcosis were reported to be transmitted
      from animals in Europe and America, suggesting that medical doctors should be
      careful in taking the history of human patients with reference to their contacts
      with animals. Close cooperation between medical and veterinary doctors is
      required in clinical studies on mycotic infection.

PMID- 9929575
TI  - [The Research Encouragement Award. Effects of sex hormones on sexual difference
      of experimental paracoccidioidomycosis].
AB  - Paracoccidioidomycosis is a deep mycosis in Latin America. The causative agent is
      Paracoccidioides brasiliensis, a thermal dimorphic fungus. The incidence of the
      disease is much higher in men than in women. Although one explanation is the
      inhibitive effect of estradiol on fungal growth, its effect on the yeast form
      growth of P. brasiliensis is still unclear. There is limited information on
      progesterone and testosterone, which shows weak or no effects. On the other hand,
      numerous studies on sexual differences between male and female animals have been
      made with experimental paracoccidioidomycosis. The conclusions however, remain
      unclear. The present study shows the effects of estradiol (17 beta-estradiol),
      progesterone and testosterone on the yeast form growth of P. brasiliensis, and
      the sexual difference of the susceptibility in adult BALB/c mice at the initial
      stages of infection with view of their estrous cycles and body weight. The
      inhibitive effects of estradiol, progesterone and testosterone on the yeast form
      growth of P. brasiliensis were examined using a brain heart infusion broth with
      different doses of these hormones. The inhibition by estradiol was dose-dependent
      within the range of physiological concentrations. While the inhibitive effect of
      progesterone and testosterone was very weak. The phenomenon that estradiol
      inhibited the yeast form growth of P. brasiliensis may be one important reason
      for the sexual differences of paracoccidioidomycosis. The initial stages of the
      yeast form cells of P. brasiliensis infection were evaluated by three inoculation
      routes: intravenous, intraperitoneal and intratracheal. The mice were divided
      into 6 groups, including male and female at proestrus, estrus, metestrus- I,
      metestrus- II and diestrus. Four hours after inoculation, blood samples,
      peritoneal lavage and pulmonary homogenates were collected and their colony
      forming units were examined on brain heart infusion agar plates with 1 % of
      dextrose and 50 mg per liter of chloramphenicol. In all inoculation routes, the
      clearance of the yeast cells was influenced by the estrous cycles. In particular,
      female mice at estrus, thought to have high blood estradiol levels, showed a
      marked clearance of the yeast cells from the blood, peritoneal cavity and lung.
      All female groups inoculated by any of the three different routes, showed much
      higher clearance than the male groups. These results suggest that non-specific
      host resistance to the yeast form cells of P. brasiliensis in females was much
      higher than in males. There are two explanations for the tendency of higher
      occurrence of paracoccidioidomycosis in men. One is the inhibitive effect of
      estradiol on the growth of P. brasiliensis and the other is the superior tendency
      of non-specific host resistance in females than in males. These two factors seem
      to have synergistic actions in the sexual difference of paracoccidioidomycosis.

PMID- 9929577
TI  - A case of fungemia due to Candida krusei.
AB  - A forty-eight-year old male diagnosed with acute lymphocytic leukemia was further
      complicated by Candida krusei fungemia despite introduction of fluconazole
      prophylaxis during antileukemic therapy. The fungemia subsided after intravenous
      amphotericin B therapy followed by itraconazole therapy. Multiple ulcerative
      lesions and a carcinoid lesion were observed in the transverse colon, and it was
      thought that the C. krusei had invaded from the ulcerative lesions. Azole
      antifungal agents, especially fluconazole, have frequently been used for therapy
      and the prophylaxis of fungal infections. Though infections due to fluconazole
      resistant Candida species such as C. krusei are a growing problem, in the
      hematology division of our hospital there is no evidence of an increasing
      incidence of C. krusei fungemia or an increasing rate of C. krusei in
      surveillance culture from admitted patients. However, future increases in
      infections due to fluconazole-resistant Candida species like C. krusei and C.
      glabrata are entirely possible, making it necessary to identify isolated fungi,
      perform susceptibility tests on antifungal agents against isolates, measure the
      serum concentrations of antifungal agents, and then to treat patients with the
      appropriate therapies.

PMID- 9929578
TI  - A clinical isolate of Candida palmioleophila formerly identified as Torulopsis
      candida.
AB  - A strain of yeast labeled Torulopsis candida, which was isolated from a clinical
      specimen in Canada and reported as a new opportunistic pathogen causing
      intravenous catheter-associated fungemia, was found to be a strain of Candida
      palmioleophila in a DNA-DNA reassociation experiment.

PMID- 9929580
TI  - Ploidy of serotype AD strains of Cryptococcus neoformans.
AB  - Twenty-four serotype AD strains of Cryptococcus neoformans were tested for ploidy
      and mating type. These included 13 natural isolates (1 from a patient, 1 from
      peach juice, 11 from pigeon droppings), 2 single clones from one of these natural
      isolates, 7 F1 progeny from a self-fertile strain and 2 F1 progeny of a cross
      between a strain from a patient (serotype A, alfa-mating type: MATalfa) and a
      tester strain (serotype D, a-mating type: MATa). Six strains (2 of natural
      isolates, 1 of single clone and 3 of F1 progeny) were MATalfa, 1 of F1 progeny
      was MATa, 4 (1 of natural isolate, 1 of single clone and 2 of F1 progeny) were a
      alfa-mating type (MATa-alfa) and 13 (10 of natural isolates and 3 of F1 progeny)
      were untypable. Most strains, regardless of mating type, were diploid.

PMID- 9929581
TI  - [Evaluation of the efficacy of small-dose itraconazole pulse therapy (200 mg/day)
      for tinea unguium].
AB  - Thirty-six patients with tinea unguium were treated with 200 mg of itraconazole
      daily for 7 days each month. We suggested that a patient who had a lesion in the
      thumbnail needed 5 months of treatment for mycologial cure, while in a patient
      without thumbnail lesion, 3 months of treatment was enough.

PMID- 9929579
TI  - [Pediatric onychomycosis treated with oral antifungal drugs].
AB  - Pediatric onychomycosis is a rare disease and it is difficult to decide in such
      cases whether or not an oral antifungal is indicated. We have observed 6
      pediatric cases with onychomycosis who were treated with fluconazole or
      itraconazole: four male and two female patients, ranging in age from three to 14
      years. One patient suffered infection in the fingernails and toenails. The
      etiologic organism was identified as Trichophyton rubrum. The treatment regimen
      consisted of systemically administering fluconazole to four of the patients and
      itraconazole to the other two. Treatment resulted in three of the 4 patients
      treated with fluconazole, and one of the 2 treated with itraconazole being healed
      completely. The other two patients treated with fluconazole and itraconazole
      showed an alleviation of symptoms. Further results of our study were that while
      younger patients respond quickly and positively to treatment, long-term follow-up
      is necessary even after treatment ceases due to the easy recurrence of this
      condition.

PMID- 9929582
TI  - The role of innervation in induction and differentiation of taste organs:
      introduction and background.
AB  - To establish lingual receptive fields that are the basic unit of taste function,
      ganglion cells must extend neurites of peripheral and central targets and form
      connections. This symposium concerns developmental interactions between the
      geniculate, trigeminal and petrosal ganglia and peripheral taste organs, the
      gustatory papillae and resident taste buds. Investigators present data from organ
      and tissue culture, from mice with targeted gene deletions and from grafting
      experiments, in pursuit of principles that direct early innervation of the taste
      system. The lingual ganglia and the taste papillae initially develop
      independently, but then become reciprocally dependent as ganglia drive
      neurotrophin support from gustatory papillae and the papillae require sensory
      innervation for growth and morphogenesis. The issue of subsequent taste bud
      induction is discussed with results from amphibian and mammalian models, yielding
      conclusions that are not yet totally convergent. However, an essential role for
      sensory innervation in mammalian taste bud differentiation and acquisition of
      appropriate quantitative relations between ganglion cells and target organs is
      clearly demonstrated. A working outline is presented for periods of ganglion
      cell/target organ independence and interdependence during early innervation of
      the peripheral taste system.

PMID- 9929583
TI  - Nerve dependency of developing and mature sensory receptor cells.
AB  - Old and recent data concerning development of sensory cells and trophic
      interdependency of sensory neurons and sensory cells is reviewed for the ear, the
      lateral line system, the electroreceptive system, and the taste system. All
      sensory neurons originate from placodes. However, only most ear, lateral line and
      electrosensory cells derive from placodes, while the taste sensory cell originate
      locally. All sensory cells apparently are nerve independent for their formation,
      and at least sensory cells in the ear and the taste system share the neurotrophic
      support for their specific sensory neurons. Later, most of these sensory cells
      appear to depend, to a variable degree, on some innervation for maintenance.
      While the molecular nature of the signal cascade from sensory cells to sensory
      neurons is known in at least two systems, nothing is known about the molecular
      nature of the signal cascade from the sensory neurons back to the sensory cells.

PMID- 9929584
TI  - Neurotrophic factors in the tongue: expression patterns, biological activity,
      relation to innervation and studies of neurotrophin knockout mice.
AB  - How taste buds develop and how they become innervated has been a matter of debate
      for a long time. Brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT3)
      mRNA expression patterns suggested a possible involvement in lingual gustatory
      and somatosensory innervation. Studies of null-mutated mice showed that BDNF-/-
      mice had few abnormal taste buds and were unable to discriminate between primary
      tastes. NT3-/- mice had a severe loss of lingual somatosensory innervation. These
      novel findings may have clinical implications in rare human conditions such as
      familial dysautonomia and/or in more common cases of problems with loss of taste
      and sensation in the mouth such as those seen after injury to the nerves, either
      by accident or following oral/facial surgery. Knowledge about which proteins that
      are required to stimulate nerve fibers to grow into mucous membranes of the oral
      cavity during development suggests that these same proteins might become helpful
      in stimulating regeneration of injured nerves in patients, perhaps helping them
      to regain lost taste and sensory functions. Here, the presence of glial cell
      derived neurotrophic factor (GDNF) families of neurotrophic factors and receptors
      in the tongue is also discussed. Further, a model for the development and
      innervation of taste buds in mammals is proposed.

PMID- 9929585
TI  - Taste neurons have multiple inductive roles in mammalian gustatory development.
AB  - The embryonic loss of brain-derived neurotropic factor (BDNF)-dependent taste
      axons in bdnf null mutant mice secondary impairs the development of gustatory
      epithelia and taste buds. In normal mice gustatory development continues for at
      least two weeks postnatally as axons promote taste bud formation. We conclude
      that taste axons in the fungiform, foliate, vallate and nasopalate papillae: i)
      promote papilla development, and ii) establish competent gustatory cells and iii)
      mature taste buds. Hence, gustatory innervation contributes critically to at
      least three of the multiple inductive interactions controlling the development of
      mammalian gustatory structures.

PMID- 9929586
TI  - The role of innervation in the development of taste buds: insights from studies
      of amphibian embryos.
AB  - Amphibian embryos have long been model organisms for studies of development
      because of their hardiness and large size, as well as the ease with which they
      can be experimentally manipulated. These particular advantages have allowed us
      recently to test the role of innervation in the development of vertebrate taste
      buds using embryos of an aquatic salamander, the axolotl. The predominant model
      of taste bud genesis has been one of neural induction, in which ingrowing sensory
      neurites induce taste bud differentiation in the epithelium that lines the mouth
      and pharynx. However, when we prevented embryonic sensory neurons from contacting
      the oropharyngeal epithelium by using transplantation or tissue culture
      techniques, we found that taste bud differentiation was independent of nerve
      contact. Additionally, using similar types of experimental manipulations, we have
      recently shown that taste bud differentiation is not a result of interactions of
      the oropharyngeal epithelium with craniofacial mesenchyme. Surprisingly, we found
      that although taste bud genesis occurs very late in embryonic development, it is
      an intrinsic feature of the presumptive oropharyngeal epithelium extremely early,
      in fact as early as the completion of gastrulation. These data have prompted us
      to propose a new model for the development of amphibian taste buds: (i) The
      presumptive oropharyngeal epithelium is specified by the time gastrulation is
      complete; (ii) Subsequently, a distributed population of taste bud progenitors is
      set up within this epithelium via local cell-cell interactions. These progenitor
      cells give rise to taste buds, which are distributed throughout the mouth and
      pharynx. How widely applicable this model might be for the genesis of taste buds
      in other vertebrates remains to be seen. However, since it is likely that the
      taste system of axolotls more closely resembles the ancestral state from which
      both the amphibian and mammalian taste systems have evolved, it is possible that
      many of the same developmental mechanisms that give rise to amphibian taste buds
      are also used to generate the receptor organs in mammals.

PMID- 9929587
TI  - Quantitative relationships between taste bud development and gustatory ganglion
      cells.
AB  - To determine whether patterns of taste bud innervation change during postnatal
      rat development, the number of geniculate ganglion cells that innervate single
      taste buds were quantified in adult and developing rats. While there was a large
      variation in numbers of ganglion cells that innervate individual taste buds,
      there was a high degree of organization in the system. Namely, the number of
      labeled geniculate ganglion cells innervating a taste bud was highly correlated
      with the size of the taste bud. This relationship between taste bud size and
      number of innervating ganglion cells develops over a prolonged postnatal period
      and is not established until postnatal day 40 (P40), when taste buds reach their
      adult size. In a second series of experiments, we sought to determine whether
      neural rearrangement of chorda tympani neurons is responsible for the development
      of this relationship by double-labeling single taste buds at different ages. We
      found that the number of ganglion cells innervating individual taste buds on P10
      predicts the size that taste buds become by P40. This finding suggests that
      neural rearrangement is not responsible for establishing the relationship between
      taste bud size and the number of innervating ganglion cells during development.
      More importantly, it strongly suggests that the 'neural template' for the mature
      innervation pattern is determined during early postnatal development.

PMID- 9929588
TI  - Molecular development of the olfactory nerve pathway.
AB  - There are, at least, two major questions concerning the molecular development of
      the olfactory nerve pathway. First, what are the molecular cues responsible for
      guiding axons from the nasal cavity to the olfactory bulb? Second, what is the
      molecular basis of axon targeting to specific glomeruli once axons reach the
      olfactory bulb? Studies in the primary olfactory pathway have focused on the role
      of extracellular matrix and ensheathing cells in establishing an initial
      substrate for growth of pioneer axons between the periphery and brain. The
      primary axons also express a multitude of cell adhesion molecules that regulate
      fasciculation of axons and hence may play a role in fascicle formation in the
      olfactory nerve. Although the olfactory neuroepithelium principally consists of a
      morphologically homogeneous class of primary olfactory neurons, there are
      numerous subpopulations of olfactory neurons expressing chemically distinct
      phenotypes. In particular, numerous subpopulations have been characterized by
      expression of unique carbohydrate residues and olfactory receptor proteins. Some
      of these molecules have recently been implicated in axon guidance and targeting
      to specific glomeruli.

PMID- 9929589
TI  - Central olfactory structures in Pax-6 mutant mice.
AB  - During the development of the olfactory system, cells located in the olfactory
      placode/olfactory pit send their axons toward the rostral part of the
      telencephalic vesicles (TVs). Some of these enter the TV inducing the formation
      of the olfactory bulbs (OBs), whereas, mitral and tufted cell axons form the
      lateral olfactory tract (LOT). Our recent studies have shown that the beginning
      of the central olfactory projections is independent of the arrival of olfactory
      receptor neuron (ORN) axons to the TV. Here we have used the mouse carrying a
      mutation in the Pax-6 gene to study whether the nasal olfactory structures
      intervene in the formation of central olfactory structures. This mutant as well
      as lacking a nose and eyes, is reported to lack olfactory epithelium and OB.
      However, we have found an ovoid cellular structure localized in the rostral part
      of the brain, and some cells in this structure project axons toward the piriform
      cortex forming a presumptive LOT. We conclude that the referred structure is an
      OB, which fails to develop because the mutation in the Pax-6 gene affects the
      formation of nasal structures. As such, fibers of the ORNs are necessary for the
      protrusion and layered formation of the OB, but these inputs are not necessary
      for the establishment of the central olfactory projections.

PMID- 9929590
TI  - Compensatory responses to early olfactory restriction.
AB  - The emphasis on the effects of early olfactory restriction has been on the
      deleterious nature of the consequences of this abnormal early experience. While
      these effects are certainly present and dramatic, it is also the case that the
      olfactory system is left fairly intact by this experimental manipulation. If one
      asks what mechanisms may account for the preservation of the developing olfactory
      system in the face of diminished activity, there are a number of neural responses
      that could help the system compensate for the damage inflicted upon the system by
      the loss of early sensory stimulation. I describe what may be compensatory
      responses to the decrease in dopamine, the increase in norepinephrine, the
      structural changes induced in the glomeruli and the increase in cell death within
      the olfactory bulb that follow neonatal unilateral naris occlusion.

PMID- 9929591
TI  - Induced peripheral sensitivity in the developing vertebrate olfactory system.
AB  - The high dimensionality and unpredictability of the chemical world makes it
      difficult for the olfactory system to anticipate relevant stimuli and construct
      neural filters accordingly. A developmental solution to this problem would be to
      alter the sensory surface according to environmental conditions so as to enhance
      sensitivity to molecules of particular relevance. Evidence for this has been
      obtained in the rabbit. By feeding pregnant does aromatic juniper berries, it
      could be shown that newborn, weanling and even adult animals demonstrate a
      preference for juniper odor without subsequent postnatal experience, and that
      this is associated with enhanced peripheral sensitivity for juniper odor as
      measured by electro-olfactogram (EOG). This is consistent with the report that in
      young salmon olfactory imprinting is associated with enhanced, odor-specific
      sensitivity of receptor cells as measured by patch clamp. The mechanisms
      underlying such changes are unknown, including the extent to which they are a
      particular feature of developing systems.

PMID- 9929592
TI  - Occurrence of ENaC subunit mRNA and immunocytochemistry of the channel subunits
      in taste buds of the rat vallate papilla.
AB  - Epithelial Na+ channels (ENaCs) are thought to mediate the amiloride-blockable
      salt taste. The rat vallate papilla does not contribute to amiloride-blockable
      salt taste, yet the presence of ENaC-mRNA in this tissue has been reported. Is
      ENaC actually contained in the taste cells, or is it merely present in the
      supporting lingual epithelium? To avoid contamination by ENaC contained in the
      lingual epithelium, we physically isolated taste buds from the vallate papilla
      and used mRNA purification followed by reverse transcriptase polymerase chain
      reaction (RT-PCR) to investigate the presence of ENaC-type message in the
      isolated buds. mRNA of alpha-, beta- and gamma-subunits was detected, the alpha
      signal being the strongest. These results provide first molecular evidence for
      the presence of ENaC subunits in taste buds that were isolated from the posterior
      tongue and were free of epithelial contamination. In addition, we used
      immunohistochemistry to show ENaC-like reactivity in posterior tongue taste
      cells. Interestingly, the immunoreactivity was not predominantly apical but was
      intracellular and close to or at the basolateral membrane. The function of
      basolateral ENaC-type channels is unknown. Possibly, the channels are normally
      closed or of very low open probability in the resting state.

PMID- 9929593
TI  - Salty and sour transduction. Multiple mechanisms and strain differences.
AB  - The amiloride-sensitive and -insensitive components of salt- and acid-induced
      responses in C57BL/6 and BALB/c mouse nondissociated taste cells were examined
      using the whole-cell clamp technique and localized taste stimulation method. Both
      amiloride-sensitive and -insensitive components were involved in a salt-induced
      depolarizing response. The taste cells of both mouse strains exhibited an
      amiloride-insensitive salt-induced response, which consisted of multiple
      components. In C57BL/6 mice, an amiloride-sensitive strain, more than 60% of salt
      induced responses were amiloride-sensitive at the apical membrane, whereas in
      BALB/c mice, an amiloride-insensitive strain, less than 40% of responses were
      amiloride-sensitive. All the acid-induced responses in taste cells examined were
      insensitive to amiloride, and were markedly suppressed by the Cl- channel
      blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB). These results
      suggest that multiple, different transduction mechanisms are involved in, and
      contribute to salty and sour transductions. In addition, we found that strain
      differences exist in salty transduction.

PMID- 9929594
TI  - The arginine taste receptor. Physiology, biochemistry, and immunohistochemistry.
AB  - The amino acid, L-arginine (L-Arg), is a potent taste stimulus for the channel
      catfish, Ictalurus punctatus. Receptor binding studies demonstrated a high
      affinity binding of L-Arg to putative taste receptor sites. This binding could be
      inhibited by preincubation of the tissue in the lectins Phaseolus vulgaris
      agglutinin (PHA) and Ricinus communis agglutinin I (RCA I). Neurophysiological
      studies demonstrated that the L-Arg receptor is a stimulus-gated ion channel type
      receptor whose conductance was stimulated by L-Arg and inhibited by D-arginine (D
      Arg). To purify the receptor we subjected CHAPS solubilized partial membrane
      preparation from barbel epithelium to RCA I lectin affinity chromatography. The
      bound proteins were eluted with D-galactose. When these proteins were
      reconstituted into lipid bilayers, L-Arg activated single channel currents with
      conductances between 45 and 85 pS. Sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) of the eluted protein showed a distinct band at
      approximately 83 kDa. Polyclonal antibodies raised against this 83-kDa band in
      guinea pigs reacted with numerous small (approximately 1 micron) sites within the
      taste pore of every taste bud when applied to fixed nonpermeabilized barbels.
      This observation suggests that the antibodies recognize an externally-facing
      epitope of the putative Arg receptor. The antibodies also inhibited L-Arg
      stimulated currents in reconstitution studies. Sephacryl S-300 HR chromatography
      of the eluant from the affinity column showed a high molecular weight peak (> 700
      kDa) which was recognized by the antibodies. Reconstitution of the protein from
      this peak into a lipid bilayer resulted in L-Arg-stimulated channels that could
      be inhibited by D-Arg. This high molecular weight component may be aggregates of
      the arginine taste receptor.

PMID- 9929595
TI  - New aspects of chemoreception in flies.
AB  - For studies of insect taste the sensory cells of labellar taste hairs on the
      proboscis of calliphorid flies (e.g., Phormia) are preferred objects. Three
      sensory cells are electrophysiologically characterized: a sugar cell, a water
      cell and a cation or salt cell. Studying hairs on legs and proboscis of other
      families of flies we recently obtained results that extend our knowledge about
      the complexity of food detection in flies. The hoverfly Eristalis tenax
      (Syrphidae family) feeds on nectar and pollen of flowers. While nectar is
      recognized via the sugar cell, the so-called salt cell is activated by low
      concentrations of a water-soluble substance in extracts of pollen. From several
      tested pollen constituents only proline, an essential amino acid for pollen
      germination, stimulates the salt cell. The discrimination between salt and pollen
      in behavioral tests can be explained by the finding that the water cell remains
      active in the presence of pollen extract, but is inhibited by salts. Obviously
      the water cell activity is involved in the feeding decision. We already described
      a similar situation in Phormia, where the salt cell activity only elicits feeding
      behavior when the water cell is active too. In contrast to the sugar cells of
      species of flies studied so far the sugar cell of the house fly Musca domestica
      (Muscidae family) is highly sensitive to lactose, a disaccharide (beta
      galactoside (1-->4) glucoside) naturally occurring only in the milk of mammals.
      Thus sugar spectra adapt to special environmental food situations. The fifth
      tarsomere of the forelegs of Musca bears besides two D-hairs 46 hairs of the B
      type. The B-hairs are functionally not uniform in contrast to their structural
      identity. Only two hairs, the 'water hairs,' contain a water cell beside a
      spontaneously firing cell, but no sugar cell. Other examples of diversity are
      hairs that contain apart from the classical sugar cells, additional cells which
      react either to p-nitrophenyl-beta-galactoside, but not to the chemically related
      lactose, or to p-nitrophenyl-alpha-glucoside. Therefore the rule established for
      the labellar taste hairs that each hair type contains the same physiological
      equipment of sensory cells, does not hold for the taste hairs of the legs.

PMID- 9929596
TI  - Noise analysis of the quinine-induced current in frog taste receptor cells.
AB  - It has been shown that quinine, a bitter tasting substance, induces a cationic
      membrane current in frog taste receptor cells. We analyzed the quinine-induced
      current fluctuation to further characterize the cationic channel conducting the
      current. Taste cells were enzymatically isolated from fungiform papillae of the
      bullfrog tongue. Membrane currents were recorded under voltage-clamp by using the
      whole-cell patch clamp technique. A Cs(+)-containing pipette solution was used to
      block K+ currents. When quinine was bath applied, it induced a steady inward
      current in cells held at -60 mV. The current data were digitized at a sampling
      frequency of 2 kHz after having been low-pass filtered (cut-off frequency, 1
      kHz). The spectral density distribution was calculated by 1024 points fast
      Fourier transform (FFT), and was fitted by a sum of two Lorentzian functions,
      with corner frequencies at 10-20 Hz and at 90-120 Hz. The single-channel
      conductance calculated from the variance versus mean current plot was 5 pS in a
      normal saline solution containing 1.8 mM Ca2+. In a nominally Ca(2+)-free
      solution, the single-channel current was doubled. Our previous study has shown
      that the quinine-induced current is enhanced in low extracellular [Ca2+]. This
      enhancement could be partly attributable to the Ca2+ suppression of the single
      channel conductance.

PMID- 9929597
TI  - Molecular cloning and taste bud-specific expression of a novel cyclic nucleotide
      gated channel.
AB  - Cyclic nucleotide-gated (CNG) channels serve as downstream targets of signaling
      pathways in vertebrate photoreceptor cells and olfactory sensory neurons. For
      taste signaling as well, a great deal of information is available predicting the
      presence of a CNG channel, but no report has been presented on its molecular
      entity. Here we report on molecular cloning and functional expression of a taste
      bud-specific CNG channel tentatively named CNGgust. Reverse transcriptase
      polymerase chain reaction (RT-PCR) primers were synthesized according to some
      amino acid sequences generally conserved in many CNG channels. RT-PCR was
      conducted using rat circumvallate papillary mRNA-derived cDNA as a template to
      obtain positive clones. A corresponding genomic DNA clone was then obtained by
      screening from a genomic DNA library. Dissecting the entire structure of this
      gene, we found that the encoding protein had an amino acid sequence similarity of
      80% to each of retina and olfactory CNG channels. It was also found by
      immunostaining with a specific antibody that this gustatory CNG channel (CNGgust)
      is localized in the tongue and also expressed specifically on the pore side of
      each taste bud in the circumvallate papillae. Electrophysiological experiments
      demonstrated that CNGgust resided in a functional state. All these data suggest
      that CNGgust may be involved in taste signal transduction in sensory cells.

PMID- 9929598
TI  - Behavioral and single chorda tympani taste fiber responses in the common
      marmoset, Callithrix jacchus jacchus.
AB  - Gustatory responses of the common marmoset were studied using single fiber
      recordings from chorda tympani (CT) nerve and two bottle preference (TBP) tests.
      Hierarchical cluster analysis of 43 fibers' response profiles revealed 3 major
      clusters of fibers characterized by predominant sensitivity to sweeteners (S
      cluster), bitter compounds (Q cluster) or acids (H cluster). NaCl as well as LiCl
      did not stimulate CT taste fibers. The TBP tests showed relationship between a
      compound's ability to stimulate the taste fibers and the animals' consumption.
      Activity in the S cluster was associated with preference, while the activity in
      the Q cluster was associated with rejection. Marmosets neither preferred nor
      rejected sweeteners which did not stimulate any CT fibers.

PMID- 9929599
TI  - Dietary fat preferences are inversely correlated with peripheral gustatory fatty
      acid sensitivity.
AB  - We previously demonstrated that taste receptor cells (TRCs) respond to cis
      polyunsaturated fatty acids (PUFAs) through an inhibition of delayed rectifying K
      channels (KDR), which may represent the transduction mechanism for dietary fat.
      To determine if there is a link between the sensitivity of fungiform TRCs to
      PUFAs and dietary fat preferences, we compared the PUFA-sensitivity of TRCs using
      patch clamp techniques from Osborne-Mendel (O-M) and S5B/Pl rats, which display
      dietary preferences for fat over carbohydrate and carbohydrate over fat,
      respectively. In isolated TRCs, the PUFAs, linoleic (C18:2), linolenic (C18:3)
      and arachidonic acid (C20:4) inhibit KDR in a concentration-dependent manner in
      both strains, while the unsaturated lauric acid (C12:0) was ineffective. KDR from
      TRCs of S5B/Pl rats were significantly more sensitive to inhibition by all three
      PUFAs (10 microM) than were TRCs from O-M rats. We are currently investigating
      whether this differential responsiveness is due to (i) the relative affinity of
      the interaction between cis-PUFAs and the delayed rectifying K channels or (ii)
      the relative density of delayed rectifying K channels in the two rat strains.
      Whatever the mechanism, these data suggest an inverse correlation between
      peripheral gustatory sensitivity to PUFAs and the dietary preference for fat.
      This finding may provide insight into the mechanism for sensing dietary fat that
      allows the S5B rats to reduce fat intake on a high-fat diet and avoid the obesity
      which results when O-M rats eat a high-fat diet.

PMID- 9929600
TI  - Taste preference in nonhuman primates to compounds sweet in man.
AB  - Primates have stimulated more interest than any other group as humans are ranked
      in this same mammalian order. Gustatory responses of human and nonhuman primates
      have already been compared for compounds such as monosaccharides,
      oligosaccharides, polyols, amino acids, dipeptides, proteins, dihydrochalcones,
      sulfamates, saccharin, acesulfame, diterpenes or urea derivatives, all known to
      be sweet in man. But no rational comparison in primates has been attempted. Using
      a structure-activity relationship study in primates, it is now possible to
      classify the primate sweetness receptors into four types according to the
      behavioral responses observed from various selected compounds sweet in humans.
      The four types are represented by (1) the Callitrichidae and (2) the Cebidae,
      both from the infraorder Platyrrhini (New World monkeys), (3) the Lemuridae and
      Lorisidae, from the suborder Prosimii (prosimians), and (4) the Cercopithecidae
      (Old World monkeys), Hylobatidae (lesser apes), Pongidae (great apes), and
      Hominidae (humans) from the infraorder Catarrhini (Old World simians). By a
      comparative study of the putative receptor recognition sites postulated for each
      type of receptor, it is inferred that the Callitrichidae (marmosets and tamarins)
      have retained the most primitive sweetness receptor among primates. As we believe
      that the evolution of the sweetness receptor is a key factor involved in the
      raising of nonhuman primates from a 'primitive grade' towards a more 'advanced'
      or 'simian grade,' the possible phylogenetic implications of these findings will
      be discussed.

PMID- 9929601
TI  - Identification and characterization of human fructose or glucose taste variants
      with hypogeusia for one monosaccharide but not for the other.
AB  - Human psychophysical functions for sweetness are similar for sucrose and
      fructose, but different for glucose, and suggest different mechanisms for
      fructose and glucose. Drosophila behavioral and electrophysiological data are
      similar to the human data and indicate separate receptor cell mechanisms for the
      monosaccharides. Moreover, fructose 'nontasters' (NTs) and glucose NTs have been
      identified in two Drosophila species. Identification of human NTs would confirm
      separate mechanisms and could lead to identification of proteins in human sweet
      taste by molecular genetic techniques. To identify human NTs, we first obtained
      responses for sucrose, fructose and glucose from 20 subjects. They tasted seven
      concentrations of each sugar (2-128 mM), paired with water, and indicated the
      sweeter of each pair. Functions for recognition indices (RIs) (proportion of
      subjects recognizing the sugar as sweeter) were similar for sucrose and fructose
      and different for glucose; this result agrees with the previous studies and
      supports different mechanisms for the monosaccharides. At 128 mM, RIs for all
      three sugars were 1.0; this result is consistent with the monogeusia reported by
      Breslin et al. for concentrations higher than those tested here. Eleven rising
      phase concentrations (10-35 mM fructose, 10-90 mM glucose) then were tested on 32
      subjects. A statistically significant interaction indicated different regression
      slopes and supported different monosaccharide mechanisms. From these data,
      positive identification values (PIDs) (lowest concentration at which the sugar
      always was judged sweeter than the water) were determined for each subject. The
      fructose log(PID) and glucose log(PID) data were not well correlated; thus
      separate mechanisms were supported further. Next, NT traits were defined by
      log(PID)s > or = 2 SD above the mean for one sugar, while the PID for the other
      remained within 1 SD of the population mean log(PID). Ninety-two subjects were
      screened to identify 12 glucose NTs and four fructose NTs. Two glucose NTs and
      three average subjects were tested in six additional sessions. The NTs showed an
      experience-induced change: there was a statistically significant reduction of
      glucose PIDs, but not of fructose PIDs. No change occurred in PIDs of the average
      subjects for either sugar.

PMID- 9929602
TI  - Expression and functional analysis of olfactory receptors.
AB  - The olfactory system recognizes and discriminates myriads of odorants of diverse
      molecular structure. This task is supposed to be accomplished by a large array of
      seven-transmembrane domain receptors encoded by a multigene family. Although
      circumstantial evidence suggests that the identified genes encode odorant
      receptors, unequivocal proof requires demonstration that the resulting proteins
      should be able to interact with odorous molecules and couple via G proteins onto
      second messenger cascades. This goal can be achieved by heterologous expression
      of receptor proteins in surrogate eucaryotic cells, although the task is
      complicated by the diversity of putative odorous ligands and the large size of
      the receptor family. Employing the baculovirus/Sf9 cell system it was found that
      receptor proteins can be expressed at high levels. Stimulating receptor
      expressing Sf9 cells with a mixture of numerous odorous compounds elicited a
      significant and dose-dependent second messenger response, which was never
      observed in control cells. Assaying a large panel of odorous compounds, including
      representatives of different odor classes and compounds of different chemical
      classes revealed that distinct receptor subtypes respond to certain odorants but
      not to others. Graded responses to only a subset of odorants indicate that the
      heterologous expressed receptor types have a selective but relatively broad
      ligand specificity. The easily manipulated bacterial system was employed to
      produce olfactory receptor proteins in large quantities. It was solubilized from
      inclusion bodies and upon reconstitution in liposomes displayed specific
      interaction with odor ligands.

PMID- 9929604
TI  - Organizational complexity in lobster olfactory receptor cells.
AB  - The current working model of transduction in lobster olfactory receptor cells
      suggests that: (1) inositol-1,4,5-triphosphate (IP3) is the excitatory olfactory
      second messenger in these cells; (2) activation of the cell also involves a
      secondary, current-carrying channel; and (3) the phosphoinositol pathway works in
      parallel to a second, cyclic nucleotide-mediated signaling pathway that provides
      input of opposite polarity into the cell. The complexity of intracellular
      signaling in lobster olfactory receptor cells renders the cells capable of fine
      tuning, and even integrating, the signal they send to the brain.

PMID- 9929603
TI  - Genome dynamics, evolution, and protein modeling in the olfactory receptor gene
      superfamily.
AB  - The human olfactory subgenome represents several hundred olfactory receptor (OR)
      genes in a dozen or more clusters on several chromosomes. One OR gene cluster on
      human chromosome 17 has been characterized by us in detail. Based on a large
      scale DNA sequence analysis, we have identified events of gene duplication and
      fusion as well as the generation of pseudogenes. The latter instances of 'gene
      death' could underlie the widespread phenomenon of human specific anosmias.
      Sixteen OR coding regions were found on this cluster, and six of them are
      pseudogenes. One of these pseudogenes, OR17-23, was found to be an intact open
      reading frame in an old world monkey. This may be a reflection of an OR
      repertoire diminution in man. A homology model of the OR protein was constructed
      by utilizing the rich information available on approximately 200 OR sequences.
      The putative odorant complementarity determining regions (CDR) was found to
      consist of 20 hypervariable residues facing an interior caving defined by
      transmembrane helices 3, 4 and 5. Such a model could be useful in analyzing
      additional OR gene sequences in the human genome in terms of odorant binding.

PMID- 9929605
TI  - Role of cyclic GMP in olfactory transduction and adaptation.
AB  - The detection of odor molecules by vertebrate olfactory receptor neurons (ORNs)
      involves signal transduction mechanisms that are thought to occur primarily
      through a cyclic adenosine monophosphate (cAMP)-mediated second messenger
      pathway. There has been intense debate whether cAMP is the sole second messenger
      responsible for all excitation and adaptation. The recent identification of a
      distinct form of odor adaptation that depends on the carbon monoxide/cyclic
      guanosine monophosphate (cGMP) second messenger system demonstrates that cAMP
      alone cannot account for all phases of adaptation and that multiple second
      messenger pathways exist in ORNs to perform distinct but closely related
      olfactory functions.

PMID- 9929606
TI  - Visualizing odor detection in olfactory cilia by calcium imaging.
AB  - To visualize odor detection in individual cilia of olfactory sensory neurons we
      have developed a new approach by using high-resolution calcium imaging
      techniques. Laser scanning confocal microscopy revealed, for the first time, that
      odor stimuli induce transient Ca2+ elevations in single olfactory cilia.
      Pharmacological analysis indicates that these Ca2+ signals depend entirely on
      Ca2+ entry through activated cyclic nucleotide-gated (CNG) channels. This novel
      approach enables us to monitor the initial steps leading to olfactory perception
      in a spatially and temporally resolved manner.

PMID- 9929607
TI  - An analysis of odorant-induced currents in on-cell patches on mammalian olfactory
      receptor neurons.
AB  - Because of the difficulty of obtaining odorant-induced currents in mammalian
      olfactory receptor neurons using whole-cell recording, we have developed a
      mathematical model of the electrical circuit of the patch and rest-of-cell. This
      can be used to quantitatively analyze on-cell patch pipette currents in response
      to perfusion of the cell by solutions containing odorants or other compounds that
      can alter membrane conductance or cell potential. We have analyzed pipette
      currents from on-cell patches of olfactory receptor neurons (ORNs) dissociated
      from adult rats. Initially, we perfused the ORNs with a high (100 mM; control 10
      mM) KCl solution, which immediately induced a current flux from cell to pipette
      of a magnitude to imply a depolarization of approximately 52 mV, close to the
      value predicted from the Nernst equation (56 mV), and no change in the patch
      conductance. In contrast, perfusion by a cocktail of five cyclic adenosine-3',5'
      monophosphate (cAMP)-stimulating odorants (cineole, n-amyl acetate, methyl
      salicylate, limonene and alpha-pinene, each at a concentration of 1 mM), after a
      delay of 4-10 sec, induced a current flux from pipette into the cell. Data in
      normal [Ca2+] and [Mg2+] implied an average patch conductance increase of
      approximately 36 pS, a cell depolarization of approximately 13 mV and an odorant
      induced single channel conductance of approximately 16 pS. In low [Ca2+] and no
      Mg2+ approximately 40% of cells responded to odorants, with an induced current
      flow from cell to pipette implying a patch conductance increase of approximately
      115 pS and cell depolarization of approximately 32 mV. The results were
      consistent with the odorants gating cAMP-gated cation channels. This analytical
      approach, which enables estimates of odorant-induced voltage and conductance
      changes to be made from changes in pipette current, should also be of general use
      for comparing cell responses to different perfusing solutions.

PMID- 9929608
TI  - Involvement of genes encoding a K+ channel (ether a go-go) and a Na+ channel
      (smellblind) in Drosophila olfaction.
AB  - We have investigated the roles of the putative cyclic nucleotide-modulated K+
      channel subunit encoded by the ether a go-go (eag) gene and a voltage-gated Na+
      channel, smellblind (sbl), encoded by the paralytic (para) locus in odorant
      responsiveness and cell excitability in Drosophila melanogaster. Three
      independent mutant alleles of eag revealed reduced antennal responsiveness in
      adult flies to a subset of odorants, all having short aliphatic side chains:
      ethyl butyrate (EB), propionic acid, 2-butanone and ethyl acetate (manuscript
      submitted). Loose patch recordings revealed that significantly fewer eag antennal
      neurons responded to EB compared to control neurons. As expected if Eag were
      involved in odor transduction, fewer EB-induced inhibitory responses were
      observed in eag mutants and focal application of high K+ saline to sensillae
      altered the excitability of the majority of neurons from wild-type, but not eag,
      antennae. Interestingly, there were fewer excitatory odorant responses dependent
      on extracellular Ca2+ in eag neurons. In contrast to the involvement of Eag in
      adult olfactory neuron odorant transduction, we found no evidence that adult sbl
      and allelic olfactory D (olfD) gene mutants were defective in their behavioral
      response to a complex attractive odor. Furthermore, electrophysiological analyses
      of adult sbl and olfD mutants revealed normal electroantennogram responses to a
      broad range of individual pure odorants and no changes in the excitable
      properties of olfactory neurons as determined by loose patch recordings.

PMID- 9929609
TI  - Generation of neurons from a nonneuronal precursor in adult olfactory epithelium
      in vitro.
AB  - Within the olfactory epithelium is a stem cell which can divide and differentiate
      to produce new sensory neurons. The identity of the neuronal stem cell is unknown
      but one candidate is the horizontal basal cell which lies adjacent to the
      basement membrane and expresses keratin. Previous attempts to generate mature
      sensory neurons from purified horizontal basal cells in vitro were unsuccessful.
      We show here for the first time that olfactory neurogenesis can be reproduced in
      vitro from partially-purified cultures of adult rat precursor cells cultivated in
      a serum-free medium. Rat olfactory epithelium was dissected from the nasal septum
      and separated from the underlying lamina propria, and its cells were dissociated
      and grown in a medium containing epidermal growth factor for 5 days.
      Immunochemistry showed that only supporting cells (SUS1-positive) and horizontal
      basal cells (keratin-positive) survived for this period. At day 6, the cells were
      stressed either by passaging them or by a simple mechanical stress. In each case,
      a morphological and immunological differentiation was observed within 24-48 hr.
      Newly formed bipolar cells were found to be S100-, glial fibrillary acidic
      protein (GFAP-), neural cell adhesion molecule (N-CAM+), and/or microtubule
      associated protein 5 (MAP-5+). After passaging 14% of the surviving cells were
      immature neurons (MAP-5+) and 4% were mature olfactory neurons (MAP-5+) and
      olfactory marker protein (OMP+)). In addition the same experiment was conducted
      on transgenic mice in which the lacZ gene was linked to the OMP promoter. Using 5
      bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining we showed that
      OMP+ cells disappeared before day 5 in culture but reappeared after passaging.
      These results suggest that olfactory sensory neurons can arise from a non
      neuronal precursor, probably the keratin-positive horizontal basal cell.

PMID- 9929611
TI  - Proliferation decrease in the olfactory epithelium during postnatal development.
AB  - Olfactory sensory cells are replaced continuously throughout the life of an
      animal. In postnatal rats proliferation density decreases dramatically, and
      continues to decrease into adulthood at least up to 11 months of age. This is
      true in both the basal cell and supporting cell populations. However, correlation
      analysis revealed there was no correlation in mitotic rate between the two cell
      types, suggesting that proliferation of the two cell types is regulated
      differently. With age, the rat body size and the area covered by olfactory
      epithelium increases. We present evidence that supporting cell proliferation
      provides only for growth, whereas proliferation of basal cells provides for both
      growth and replacement. Further, we present evidence that in older animals the
      sensory cells live longer than they do in younger animals.

PMID- 9929610
TI  - Factors regulating neurogenesis and programmed cell death in mouse olfactory
      epithelium.
AB  - To identify factors regulating neurogenesis and programmed cell death in mouse
      olfactory epithelium (OE), and to determine the mechanisms by which these factors
      act, we have studied mouse OE using two major experimental paradigms: tissue
      culture of embryonic OE and cell types isolated from it; and ablation of the
      olfactory bulb ('bulbectomy') of adult mice, a procedure that induces programmed
      cell death of olfactory receptor neurons (ORNS) and a subsequent surge of
      neurogenesis in the OE in vivo. Such experiments have been used to characterize
      the cellular stages in the ORN lineage, leading to the realization that there are
      at least two distinct stages of proliferating neuronal progenitor cells
      interposed between the ORN and the stem cell that ultimately gives rise to it.
      The identification of a number of different factors that act to regulate
      proliferation and survival of ORNs and progenitor cells suggests that these
      multiple cell stages may each serve as a control point at which neuron number in
      the OE is regulated. Our recent studies of neuronal colony-forming progenitors
      (putative stem cells) of the OE suggest that even these cells, at the earliest
      stage in the ORN lineage so far identified, are subject to such regulation: if
      colony-forming progenitors are cultured in the presence of a large excess of
      differentiated ORNs, then the production of new neurons by progenitors is
      dramatically inhibited. This result suggests that differentiated ORNs produce a
      signal that feeds back to inhibit neurogenesis by their own progenitors, and
      provides a possible explanation for the observation that ORN death, consequent to
      bulbectomy, results in increased neurogenesis in the OE in vivo: death of ORNs
      may release neuronal progenitor cells from this inhibitory signal, produced by
      the differentiated ORNs that lie near them in the OE. Our current experiments are
      directed toward identifying the molecular basis of this inhibitory signal, and
      the cellular mechanism(s) by which it acts.

PMID- 9929612
TI  - Differentiation in an olfactory cell line. Analysis via differential display.
AB  - The olfactory epithelium is a unique system, in which new neurons are continually
      generated throughout adult life. Olfactory neurons are derived from stem cells
      that lie adjacent to the basal lamina of the olfactory epithelium; these stem
      cells divide several times and their progeny differentiate into mature sensory
      neurons. In our laboratory immortalized cell lines have been derived from these
      dividing cells. The morphology of these cell lines and their expression of
      neuronal markers varies with culture conditions. When grown in low serum medium
      one of these cells lines, OLF 442, differentiates by extending long neurites and
      increasing its expression of neurofilament and B50/GAP43 proteins at the same
      time reducing expression of glial fibrillary acidic protein (GFAP).
      Identification of differentially expressed mRNA in cell lines has previously
      relied on both screening for known markers, and the use of subtractive techniques
      for identification of unique mRNA species. The differential display technique
      allows simultaneous detection of differentially expressed mRNA at different time
      periods and growth conditions. A modified Liang and Pardee differential display
      technique was used to screen OLF 442 over a number of time intervals in serum
      depleted media, and compared with OLF 442 grown in complete media. The
      differentially displayed fragments were cloned and sequenced, leading to the
      identification of a number of sequences, both known and unknown. The known
      sequences include SPARC (encoding a Ca2+ binding secreted Protein which is Acidic
      and Rich in Cysteine), which is reported to function as a modulator of the cell
      matrix, and RHAMM, the receptor for hyaluronan-mediated motility. Both the known
      and the unknown sequences are being studied further to provide insight into the
      differentiation of olfactory neurons.

PMID- 9929613
TI  - Initial development of a small subclass of rat olfactory receptor neurons
      characterized by antigenicity to HSP 70.
AB  - We have described a subclass of rat olfactory receptor neurons (ORNs) that
      constitutively shows immunoreactivity with a monoclonal antibody (2A4) directed
      to the 70-kDa heat shock protein. These ORNs are scattered nonuniformly in
      olfactory epithelium (OE) Zones II-IV and project to just 2-3 glomeruli at
      consistent locations in the ventrolateral and ventromedial olfactory bulb (OB)
      via consistent pathways. To examine early neurogenesis of this subpopulation,
      paraffin sections from embryonic day 14 (E14) to postnatal day 63 (P63) rats were
      examined using immunoperoxidase techniques. Results show: (i) a few faintly
      reactive 2A4(+) ORNs first appear between P7 and P10. Their numbers (and
      immunoreactivity (IR) intensity) increase to adult levels by P21, reach a peak
      density approximately twice that of adults by P49, and then decline to adult
      values by P56. (ii) tritiated thymidine [3H]TdR autoradiographic birthdating
      studies show that the vast majority of 2A4(+) ORNs present at P21, when adult
      2A4(+) ORN densities are first observed, were 'born' postnatally, between P3 and
      P10. (iii) The initial 2A4(+) ORN OE zonal distribution is the same as in adults.
      (iv) Through P21 2A4(+) ORN cell bodies are situated quite apically within the
      OE, but then assume more basal locations as well. (v) In the OB, glomeruli
      showing 2A4(+) axons appear in some animals as early as P14 and in all animals by
      P21. Initial location of the (+) glomeruli is similar to that of adults, despite
      extensive growth and development postnatally. The postnatal neurogenesis of the
      2A4(+) ORNs, in contrast to the very early (E13) initial appearance of ORN
      subclasses characterized on the basis of their putative olfactory receptor mRNAs,
      indicates that different ORN subclasses may vary in the time of their initial
      neurogenesis.

PMID- 9929614
TI  - Effects of insulin-like growth factor 1 on olfactory neurogenesis in vivo and in
      vitro.
AB  - The rate of neurogenesis in the peripheral olfactory neuroepithelium is regulated
      by unknown mechanisms. The members of the insulin-like growth factor (IGF) family
      can influence neuronal generation, survival and/or differentiation. Several
      members of this family, in particular IGF-1, are expressed at high levels in the
      olfactory bulb and epithelium, where they could influence the generation and/or
      survival of olfactory receptor neurons (ORNs). To explore the role of IGF-1 in
      the olfactory epithelium (OE), we asked which cells expressed IGF-1 receptors
      (IGF-1Rs), using olfactory cell cultures and cryostat-cut tissue sections of
      neonatal (postnatal day four) and adult rat OE. An antibody specific for the
      alpha subunit of the IGF-1R densely labeled a subset of ORNs but not other cell
      types in sections and cultures. These ORNs were primarily immature, as determined
      by double labeling with neuronal markers. The number of IGF-1R-labeled cells as
      well as the levels of IGF-1R protein (determined by immunoprecipitation and
      Western blotting) decreased with age, which is consistent with normal
      developmental changes. To study IGF-1 effects in the intact animal, we infused
      IGF-1 and related growth factors into the noses of newborn Sprague-Dawley rats,
      i.e., when the epithelium is still developing. Growth factors or carrier solution
      (0.9% NaCl with 0.25% bovine serum albumin to prevent nonspecific binding) were
      applied (10 microliters) to the left nostril once per day starting shortly after
      birth on postnatal day 1 (P1), P2 and P3, and the animals were sacrificed on P4
      by decapitation. After paraformaldehyde immersion fixation, cryostat sections of
      the olfactory area of the nose were immunostained for the proliferating cell
      nuclear antigen (PCNA). Sections were position-matched by turbinate structure and
      then epithelial height and area of PCNA staining at the base of the epithelium
      (which represents division of primarily neuronal precursors) were measured by
      image analysis. Both were significantly increased by rat IGF-1 (20 ng/ml, 2.6
      nM), but not insulin (20 ng/ml, 2.6 nM) or an IGF-1 derivative, LongR3 IGF-1 (200
      ng/ml, 22 nM), that does not bind to the IGF-1 binding proteins (IGFBPs). Thus
      IGF-1 appears to influence the rate of olfactory neurogenesis, and its actions
      are not modified by the IGFBPs. These data suggest an important role for IGF-1 in
      the OE.

PMID- 9929615
TI  - Does olfactory marker protein participate in olfactory neurogenesis?
AB  - Olfactory marker protein (OMP) is a phylogenetically conserved, 19-kDa, acidic,
      soluble protein found abundantly in mature olfactory sensory neurons. Its
      function has been enigmatic although recent evidence from studies on OMP null
      mice suggests that neurons lacking OMP exhibit altered physiological activity,
      including prolonged onset and recovery kinetics following stimulation. We have
      reported increased expression of OMP in individual surviving sensory neurons that
      have been deprived of their target, the olfactory bulb. Because olfactory
      epithelia deprived of their target also exhibit an increased rate of cell
      division we investigated the effect of recombinant OMP on cell division in
      organotypic cultures of fetal rat (embryonic day 19) epithelium grown for 3 days
      in vitro. After 3 days, cultures were given a 1-hr pulse of a mitotic marker,
      bromodeoxyuridine (BrdU), fixed and prepared for immunohistochemistry to
      determine the number of proliferating cells. We found a dose-dependent increase
      in the number of BrdU-positive cells/100-mm length of epithelium. The number of
      labeled cells increased incrementally, reached a plateau at 25 pM OMP/ml culture
      medium, 50% higher than in cultures with no OMP added, and remained at that level
      at 50 and 100 pM doses. Controls included trypsinized OMP and addition of
      equivalent volumes of TRIS buffer lacking OMP. These results, taken together with
      previous studies on several growth factors indicate that regulation of
      neurogenesis in olfactory tissue is a multifactorial process and that OMP may
      play a role.

PMID- 9929616
TI  - Cell death, phagocytosis, and neurogenesis in mouse olfactory epithelium and
      vomeronasal organ after colchicine treatment.
AB  - The cytotoxic agent colchicine induced apoptotic cell death in the mouse
      olfactory epithelium and vomeronasal organ. The terminal deoxynucleotidyl
      transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling
      (TUNEL) method revealed the presence of many apoptotic bodies in the middle to
      basal region of the septal olfactory epithelium and vomeronasal organ near the
      boundary of the respiratory epithelium at 1 day after intraperitoneal (i.p.)
      injection of colchicine (4 mg/kg). In some areas of the nasal turbinates, massive
      apoptosis was observed in the olfactory epithelium. Electron micrographs showed
      that immature olfactory cells and globose basal cells were killed by the
      colchicine and had been phagocytized by the supporting cells and macrophages. In
      some areas of the nasal turbinates, mature olfactory cells were also killed, and
      thus only the supporting cells and horizontal basal cells remained in the
      epithelium. Bromodeoxyuridine (BrdU) labeling showed that regeneration occurred
      in the septum and vomeronasal organ at 4-6 days after colchicine treatment;
      however, there were no regenerated olfactory cells in some areas of the
      turbinates up to 30 days after colchicine treatment.

PMID- 9929617
TI  - ErbB-3 and ErbB-4 expression in the mouse olfactory system.
AB  - The interplay between neuregulins and the ErbB receptor family has a pivotal role
      in the development of several tissues, including the nervous system, and is
      maintained in the adult olfactory system where extensive plasticity and
      neurogenesis are retained. In the present work we show the immunohistochemical
      localization of ErbB-3 and ErbB-4 in the olfactory system of adult normal and
      lesioned mice. The expression of ErbB-3 is demonstrated to be restricted to the
      ensheathing cells of the olfactory nerve and to a few substentacular cells of the
      olfactory epithelium (OE). ErbB-3 staining circumvents the glomeruli but is never
      observed inside them or elsewhere in the adult olfactory bulb. Conversely, ErbB-4
      immunoreactivity is found in all the periglomerular and mitral/tufted cells of
      the olfactory bulb (OB) and to a minor extent in the olfactory neurons and basal
      cells of the OE. Interestingly enough, cells coming out from the rostral
      migratory stream of the subependymal layer (SEL), as well as isolated cells in
      the granule cell layer, possibly migrating cells, strongly stained for ErbB-4
      expression. Lesions of the olfactory epithelium have been performed by unilateral
      intranasal irrigation with ZnSO4 and 3 weeks after the irrigation, the olfactory
      bulbs were analyzed for olfactory marker protein (OMP), tyrosine hydroxylase
      (TH), ErbB-3 and ErbB-4 expression. In the deafferented OB, the drastic loss of
      immunoreactivity for OMP was accompanied by a strong reduction of ErbB-3
      expression. Most of the deafferented dopaminergic interneurons switched off TH
      expression. In the deafferented periglomerular and mitral/tufted cells ErbB-4
      expression was turned off and down, respectively. No differences were noted at
      the granular cell layer level in the deafferented OB with respect to control.
      Taken together our results suggest that, in normal conditions, neuregulins are
      involved in the survival of the ensheathing cells of the olfactory nerve through
      ErbB-3 activation and in the functional activity of postsynaptic neurons through
      ErbB-4 activation.

PMID- 9929618
TI  - Alterations in the neurotrophic factors BDNF, GDNF and CNTF in the regenerating
      olfactory system.
AB  - Neurogenesis, axonal outgrowth and synapse formation are usually restricted to
      specific stages during central nervous system development, but the mature
      olfactory system maintains these capacities. The cycle of neuronal turnover can
      be experimentally induced by surgical ablation of the olfactory bulb (OB). We are
      interested in the growth factor regulation of these processes and the trophic
      role played by the target tissue, the OB. We studied the immunohistochemical
      expression of three neurotrophic factors, brain derived neurotrophic factor
      (BDNF), glial cell line-derived neurotrophic factor (GDNF) and ciliary
      neurotrophic factor (CNTF) in the rat olfactory neuroepithelium (ON) and OB and
      in target-deprived ON at 1, 3 and 12 weeks post unilateral bulbectomy. We found
      BDNF immunoreactivity (IR) was restricted to the basal cells and did not alter
      postbulbectomy. GDNF-IR was expressed by mature olfactory receptor neurons
      (ORNs), their axons and target cells in the OB in controls, but was absent from
      the ON postbulbectomy. Hence, the expression of GDNF by ORNs was found to be
      target-dependent. CNTF-IR was present in ORNs and their target cells in the OB,
      in basal cells and in some immature ORNs. Postbulbectomy, CNTF-IR was unaltered
      in the basal cells, and very low levels were detectable in maturing ORNs in the
      ON. Our results indicate that these three factors may contribute to the trophic
      regulation of this neuronal pathway in a coordinated fashion. Previous work has
      shown that BDNF promotes survival of ORNs in vitro, and TrkB expression has been
      found in both immature and mature ORNs. Hence, BDNF produced by basal cells may
      be acting locally on neurons expressing TrkB. Expression of CNTF by both the
      basal cells and the ORNs suggests that it may play an integral role in this
      neuronal differentiation pathway. Finally, the expression of GDNF exclusively by
      mature ORNs in the ON, its presence in the target cells in the OB and abolition
      of expression by bulbectomy, suggests that it may be target-derived. This
      provides a major mechanism by which the bulb could exert trophic influences on
      ORNs.

PMID- 9929619
TI  - The influence of ensheathing cells on olfactory receptor cell neurite outgrowth
      in vitro.
AB  - We previously reported that laminin substrates increased primary (1 degree)
      neurite outgrowth from olfactory receptor cells (ORCs) in vitro. To further
      explore mechanisms underlying the outgrowth of ORC neurites, we have cocultured
      ORCs with the ensheathing cells (ENSH) from the olfactory nerve. ORCs were plated
      either: (i) directly on monolayers of ENSH (prepared with minor modifications as
      reported by Doucette and Devon, or (ii) on coverslips suspended above the ENSH
      monolayer to investigate diffusible trophic influences of ENSH. In addition, ORCs
      were cocultured with either olfactory bulb glia (OBG) or hippocampal astrocytes
      (HG) or grown on either laminin (LN) substrates or poly-L-lysine (PLL) controls.
      The length of ORC neurites was determined after 48 hr in vitro.
      Immunocytochemical characterization of the ENSH cultures for p75 nerve growth
      factor (NGF) receptor and glial fibrillary acidic protein (GFAP) revealed that
      those cultures contained more than 80% ENSH. In OBG cultures approximately 10%
      and in HG cultures no cells with ENSH characteristics were found. All cells with
      ENSH characteristics were also LN-immunoreactive. After 48 hr in culture ORCs had
      the longest 1 degree neurites when they were cocultured with ENSH. No significant
      differences in the 1 degree neurite length were found comparing ORCs grown
      directly on ENSH and ORCs physically separated from ENSH. ORCs cultured on HG and
      on EHS-LN showed no significant differences in the ORC 1 degree neurite length,
      but on both substrates the ORC 1 degree neurites were significantly shorter than
      on ENSH. The length of the ORC secondary neurites did not vary significantly in
      the different culture conditions. Our results suggest that while LN appears to
      contribute to ORC neurite extension, additional diffusible factors released from
      ENSH are likely to be further determinants of neurite outgrowth. Because the OBG
      and HG cocultures did not influence ORC neurite outgrowth as significantly as did
      the ENSH, it seems plausible to suggest that these diffusible factors may be
      specific to subpopulations of glial cells.

PMID- 9929620
TI  - Influence of olfactory innervation on neurogenesis in the developing olfactory
      bulb of the frog, Xenopus laevis.
AB  - Previous research on development of the Xenopus olfactory bulb from our
      laboratory has shown that mitral cells begin to differentiate after olfactory
      axons make contact with the olfactory bulb, and the number of olfactory axons is
      correlated with the number of mitral cells throughout development. In embryos,
      removal of all afferent innervation before the mitral cells begin to
      differentiate results in a failure of the bulb to form; removal of half the
      olfactory axons, results in development of half the normal number of mitral
      cells. At larval stages, transection of the olfactory nerve results in a decrease
      in the number of neurons in the olfactory bulb. Thus, the olfactory axons play a
      major role in stimulating or maintaining development of the olfactory bulb
      neurons. Since we have found that neurogenesis in the bulb continues through
      metamorphosis, the goal of the current study was to determine whether olfactory
      axons influence cell genesis and/or neuronal maturation in the larval olfactory
      bulb. To study cell genesis, we cut the olfactory nerves, and 6 days later,
      injected the animals with [3H]thymidine. After 6 hr, the animals were killed and
      the tissue was processed for autoradiography. The number of labeled cells in the
      ventricular zone of the olfactory bulb was determined in every fifth section
      through the bulb in control and experimental animals. There was no statistical
      difference (Mann-Whitney rank sum test) in the number of labeled ventricular
      cells between controls and experimentals. Thus, olfactory axon innervation does
      not appear to play a role in precursor cell division during larval development.
      To study the influence of olfactory axon innervation on the ability of newly
      generated neurons to mature, we followed the same procedures. However, the
      animals were killed 21 days after the [3H]thymidine injection. The results from
      this experiment showed that there are many fewer labeled mitral cells in the
      experimental animals at 21 days. Together these results suggest that sensory
      deafferentation influences mitral cell differentiation or survival even during
      late stages of larval development.

PMID- 9929621
TI  - Addition of new cells to the olfactory bulb of adult zebrafish.
AB  - We have been examining patterns of cell proliferation in the brain of adult
      zebrafish. Understanding this process in fish may lead to important insights due
      to the tremendous regenerative capabilities of these animals. Fish were exposed
      to a 1% solution of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) for 1 hr
      before being returned to small aquaria that received frequent water changes.
      Animals were overanesthetized and perfused with Bouin's fixative solution after
      two survival periods (4 hr or 3-4 weeks). Paraffin immunohistochemistry using a
      monoclonal antibody against BrdU was used to visualize the newly generated cells.
      Quantitative analyses were performed on serial, 10-micron sections from 4 animals
      for each survival group. Statistical determinations were based on the
      nonparametric Mann-Whitney U test. The average number of BrdU-labeled nuclear
      profiles in the bulbs, from analysis of every 5th section, was significantly
      different between the two groups (22.0 +/- 6.8 [SEM] for the 4-hr group and 136.7
      +/- 11.3 for the 4-wk group; p < 0.05). The volumes of the bulbs, however, were
      not different between the two groups (p > 0.5). These data indicate that either
      cells divided repeatedly during the longer survival period or cells migrated into
      the bulb from other brain regions. To examine this phenomenon further, the
      location of the new cells was analyzed in three mid-bulb sections (20 microns
      apart) from each animal. Both the area and number of labeled nuclei in each
      lamina were measured to obtain an average profile density. Comparison of the 4-hr
      and the 4-wk groups showed that density was significantly greater in all bulb
      layers in the long survival group (p < 0.05 for all). In the 4-hr survival group,
      cells were found mainly in the olfactory nerve layer. When examined after 4 wk,
      proportionately more labeled cells were found in the internal cell layer. This
      addition of new cells could be a result of neurogenesis, gliogenesis, and/or
      angiogenesis. We are currently performing double-labeling experiments to
      determine the types of cells that are added to the adult bulb. In addition, our
      future plans include investigating the origin of these cells and the signals that
      direct their formation.

PMID- 9929622
TI  - Odorant-binding proteins: structural aspects.
AB  - Structural data on odorant-binding proteins (OBPs), both in vertebrates and in
      insects, are reviewed and discussed. OBPs are soluble proteins interacting with
      odor molecules and pheromones in the perireceptor areas, the nasal mucus in
      vertebrates and the sensillar lymph in insects. The physiological function of
      these proteins is still uncertain, but information on their structure is abundant
      and accurate. Based on complete amino acid sequences, several subclasses have
      been identified, suggesting a role in odor discrimination. The OBPs of
      vertebrates belong to the family of lipocalins that includes proteins involved in
      the delivery of pheromonal messages. Those of insects do not bear significant
      similarity to any other class of proteins. The three-dimensional structure of the
      bovine OBP is a beta-barrel, while for insect OBPs a model has been proposed,
      mainly containing alpha-helix motifs. In some cases the amino acid residues
      involved in ligand binding have been identified with the use of photoaffinity
      label analogues.

PMID- 9929623
TI  - Evolution of olfactomedin. Structural constraints and conservation of primary
      sequence motifs.
AB  - Olfactomedin is a glycosylated extracellular matrix protein originally identified
      at the mucociliary surface of the amphibian olfactory neuroepithelium and
      subsequently localized throughout the mammalian central nervous system. Although
      olfactomedin homologues have been identified in fish, frog, rat, mouse and human,
      its function is still unknown. As a first step toward elucidating the function of
      olfactomedin, sequences of teleost, amphibian and human homologues were compared
      to identify invariant, and hence, potential functionally important motifs.
      Previous studies revealed 33% amino acid sequence identity between rat and frog
      olfactomedin in their carboxyl terminal segments. Further analysis, however,
      reveals more extensive homologies throughout the molecule. Despite significant
      sequence divergence, cysteines essential for homo-polymer formation, such as the
      CXC motif near the amino terminus, are conserved as is the characteristic
      glycosylation pattern, suggesting that these posttranslational modifications are
      essential for function. Furthermore, alignment of a region of 53 amino acids of
      fish, frog, rat and human olfactomedin reveals seven invariant residues including
      a negatively charged cluster of aspartic and glutamic acid residues. Molecular
      evolutionary genetic analysis reveals an accelerated rate of nucleotide
      substitutions in the mammalian lineage. The evolutionary rate at the protein
      level, however, is constant, indicating that evolution of olfactomedin is
      constrained by structural limitations. Whereas considerable evolutionary
      divergence is evident between fish, frog and mammalian olfactomedins,
      olfactomedins of rat and human show 98% amino acid sequence identity. It appears
      that an ancestral olfactomedin gene arose before the evolution of terrestrial
      vertebrates and evolved independently in teleost, amphibian and mammalian
      lineages. The apparent evolutionary pressure toward conservation of primary
      structure supports the notion that olfactomedin has an important function in the
      mammalian nervous system.

PMID- 9929624
TI  - Odorant-binding proteins of true bugs. Generic specificity, sexual dimorphism,
      and association with subsets of chemosensory sensilla.
AB  - Odorant-binding proteins (OBPs) in insects occur within olfactory sensilla, and
      are thought to transport chemical stimuli to receptors on dendrites of sensory
      neurons. Until recently, knowledge of OBPs in insects was limited to moths and
      Drosophila. We discovered an antennal-specific protein (Lygus [lineolaris]
      antennal protein, LAP) with a unique N-terminal sequence in the true bug, Lygus
      lineolaris. We localized LAP to antennae, determined its molecular weight (16
      kDa), and showed that while it was expressed in nymphal antennae, its levels
      dramatically increased in adults concurrent with increases in numbers of
      olfactory sensilla and electrical responses to odors. In our current study, we
      used immunological techniques to demonstrate in more detail that LAP occurs only
      in antennae, and to show its expression within Lygus species. LAP was expressed
      more in male antennae than in antennae of females for the Lygus species examined.
      Anti-LAP did not recognize antennal proteins of two other genera of bugs.
      Immunocytological studies showed LAP primarily within the sensillar lymph of type
      1 and type 4 sensilla on antennae. These observations strongly suggest LAP to be
      an OBP, and our discovery and characterization of OBPs in true bugs provides a
      third order for use in the study of evolution of OBPs in insects.

PMID- 9929625
TI  - Olfactory coding in a compound nose. Coexpression of odorant-binding proteins in
      Drosophila.
AB  - Odorant-binding proteins (OBPs) are small, soluble proteins present in the
      aqueous medium surrounding olfactory receptor neurons. Their function in
      olfaction is unknown: they have been proposed to facilitate the transit of
      hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus,
      and/or to play a role in chemosensory coding. We have examined the genomic
      organization and expression patterns of two olfactory-specific genes (OS-E and OS
      F) of Drosophila melanogaster, the products of which are members of a protein
      family in Drosophila sharing sequence similarity with moth OBPs. We found that
      the OS-E and OS-F transcription units are located < 1 kb apart. They are oriented
      in the same direction and display a similar intron-exon organization. Expression
      of both OS-E and OS-F proteins is spatially restricted to the ventrolateral
      region of the Drosophila antenna. Within this region, both OS-E and OS-F proteins
      are expressed within two different types of sensory hairs: in most, if not all,
      sensilla trichodea and in approximately 40% of the interspersed small sensilla
      basiconica. We consistently observe that OS-E and OS-F are coexpressed,
      indicating that an individual sensillum can contain more than one odorant-binding
      protein. This finding has potential implications for the roles of odorant-binding
      proteins in olfactory coding.

PMID- 9929626
TI  - Pheromones, the vomeronasal system, and communication. From hormonal responses to
      individual recognition.
AB  - The functions of the vomeronasal and olfactory systems are evaluated within the
      broad context of chemical communication in mammals. Five main points are
      stressed. First, there are a variety of types of chemical signals, ranging from
      classic pheromones to odor quality signals, all of which are important for
      communication. Second, the vomeronasal organ is primarily responsible for
      mediating responses to some, but by no means all, pheromone-like signals. Third,
      the olfactory system mediates responses to some pheromone-like signals. Fourth,
      the vomeronasal system mediates some responses to odor quality signals. Thus, not
      all receptors in the vomeronasal organ are involved in detection of pheromones.
      Fifth, the vomeronasal and olfactory systems often interact to mediate responses
      to odor signals. In sum, it is important to maintain a broad, balanced view and
      to avoid oversimplifications if we are to advance our understanding of the
      sensory mechanisms underlying responses to chemical signals and other odors.

PMID- 9929627
TI  - Vomeronasal, olfactory, hormonal convergence in the brain. Cooperation or
      coincidence?
AB  - This paper briefly reviews three topics: (a) Convergent vomeronasal and olfactory
      chemosensory input into a common circuit considered important for mating in male
      golden hamsters; (b) Apparent activation of this circuit by intracerebral
      luteinizing hormone-releasing hormone (LHRH) and (c) Interaction of the LHRH and
      the two chemosensory inputs. Mapping of c-fos protein in male hamsters mating
      with females or exposed to female pheromones indicates intense activation in the
      central vomeronasal pathways, induced by both olfactory and vomeronasal input.
      This input appears to activate the medial preoptic area, where chemosensory
      activation is greater in experienced than in inexperienced animals. Intracerebral
      injection of LHRH facilitates mating behavior and increases Fos expression in the
      medial preoptic area of mating males. Despite evidence that the release of LHRH
      in response to female chemosignals is dependent on vomeronasal input, no
      activation of LHRH neurons has been demonstrated in males exposed to such
      chemosignals. Electrical stimulation of the vomeronasal organ can induce Fos
      expression in chemosensory pathways and in medial preoptic LHRH neurons.

PMID- 9929628
TI  - Integration of chemosensory and hormonal input in the male Syrian hamster brain.
AB  - Mating in the male Syrian hamster requires the interaction of chemosensory and
      hormonal stimuli. Chemosensory cues from the vomeronasal organ and olfactory
      mucosa are transmitted through limbic nuclei that contain receptors for gonadal
      steroid hormones, including the medial amygdaloid nucleus (Me) and medial
      preoptic area (MPOA). This pathway is essential for mating, as lesions that
      interrupt transmission of chemosensory cues to MPOA will abolish copulation.
      Likewise, gonadal steroids facilitate sexual behavior through Me and MPOA, as
      demonstrated using intracranial implants in the brains of castrate males. In
      addition, odor and hormonal signals must be integrated in the brain for
      copulation to occur. Mating is prevented when olfactory bulbectomy is performed
      ipsilateral to an intracranial testosterone implant, thereby preventing the
      interaction of odors and hormones. According to our current model, hormones may
      act as a gating signal to strengthen synaptic contacts along the chemosensory
      pathway, thereby permitting or enhancing transmission of chemosensory cues.

PMID- 9929629
TI  - The human vomeronasal system. A review.
AB  - Recent publications show that the human vomeronasal organ (VNO) develops and
      grows during gestation, and is present in all adult humans. The human VNO has a
      unique ultrastructure, with elongated bipolar microvillar cells that stain with
      several immunomarkers. These cells show physiological properties similar to
      chemosensory receptor cells of other mammalian species. The adult human VNO
      displays species-specific, gender-dimorphic and highly stereospecific responses
      to ligands. The organ's local response, or electrovomerogram, is followed by
      gender-specific behavioral changes, modulation of autonomic nervous system
      function, or the release of gonadotropins from the pituitary gland. Functional
      brain imaging studies revealed consistent activation of the hypothalamus,
      amygdala and cingulate gyrus-related structures during adult human VNO
      stimulation. These findings present new information supportive of a functional
      vomeronasal system in adult humans.

PMID- 9929630
TI  - On the nature of mammalian and human pheromones.
AB  - Communication by chemical (pheromone) signals is important in many species,
      including mammals. Chemosensory and hormonal systems can interact in at least two
      ways: (i) chemosensory input, especially but not exclusively that through the
      vomeronasal organ, may elicit hormonal release, which, in turn, may facilitate
      behavioral or physiological responses; and (ii) hormones, especially steroids,
      may be essential for some responses to chemosensory, including vomeronasal,
      input. Recent, still controversial reports, suggest that chemosensory
      communication may occur in humans via a residual vomeronasal organ and that
      chemosensory/hormonal interactions also operate in humans. In this symposium
      these matters are examined critically. Johnston explores the concept of pheromone
      communication and suggests that the notion of a single-chemical 'magic bullet'
      irresistibly leading to a preprogrammed result is too simplistic despite
      documented examples of special stimuli acting via the vomeronasal organ. Meredith
      briefly reviews evidence for hormonal mediation of the effects of vomeronasal
      input; including a situation where vomeronasal and hormonal facilitation of a
      behavior appear to be interchangeable--but where vomeronasal input appears
      important only in inexperienced animals. Wood discusses evidence that the
      effectiveness of chemosensory input to particular brain nuclei depends critically
      on the simultaneous presence of a steroid hormone within the same nucleus. Monti
      Bloch presents his evidence that steroids may act as gender-specific chemical
      signals in humans, exciting an electrical response from the residual human
      vomeronasal organ and affecting human hormone levels.

PMID- 9929631
TI  - Introductory remarks on umami taste.
AB  - Psychophysical and electrophysiological studies indicated that the umami
      substances have no enhancing activity on other primary tastes. Experiments using
      amiloride clearly show that the umami component of canine chorda tympani nerve
      response to umami substances is independent of the salt component. Single fiber
      analysis of the responses of the mouse glossopharyngeal nerve and the monkey
      primary taste cortex neuron show that the responses to umami substances are
      independent of other primary tastes. A large synergism between monosodium
      glutamate (MSG) and disodium 5'-inosinate (IMP) or disodium 5'-guanylate (GMP) is
      observed in dogs and is explained in terms of allosteric effect. The order of
      intensity of umami taste induced by a mixture of 0.5 mM GMP and 1.5 mM of various
      agonists for the glutamate receptors was glutamate > ibotenate > DL(+)-2-amino-4
      phosphonobutyric acid (DL-AP4)-(+)-1- aminocyclopentane-trans-1,3-dicarboxylic
      acid (trans-ACPD). Kainate, N-methyl-D-aspartate (NMDA) and (RS)--amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA), which are agonists for ionotropic
      receptors, have no umami taste. It was concluded that the umami receptor is not
      identical to any of known glutamate receptors, and there seems to be a unique
      receptor for umami.

PMID- 9929632
TI  - Molecular and physiological evidence for glutamate (umami) taste transduction via
      a G protein-coupled receptor.
AB  - Recent molecular analyses have demonstrated that a metabotropic glutamate
      receptor, mGluR4, is expressed in taste buds from rat circumvallate and foliate
      papillae. Behavioral studies demonstrated that L(+)-2-amino-4-phosphonobutyric
      acid (L-AP4), an agonist for mGluR4 and related receptors, mimics the taste of
      monosodium glutamate (MSG) in rats. mGluR4 is known to signal through inhibition
      of the cyclic adenosine-5',3'-monophosphate (cAMP) cascade. Circumvallate and
      foliate taste buds exhibit decreases of cAMP levels following stimulation with
      MSG, and the response is potentiated by 5'-inosine monophosphate, suggesting that
      it is related to umami taste. Further, experiments on mice with the mGluR4 gene
      knocked out support the interpretation that mGluR4 is a key component in
      glutamate taste. Glutamate may also stimulate taste buds through an ionotropic
      receptor pathway. In patch-clamp studies, glutamate evokes two types of currents,
      similar to those elicited by N-methyl-D-aspartate (NMDA) and L-AP4. We speculate
      upon the significance of two glutamate receptor pathways in taste buds.

PMID- 9929633
TI  - Responses to monosodium glutamate and guanosine 5'-monophosphate in rat fungiform
      taste cells.
AB  - Monosodium glutamate (MSG) elicits a unique taste sensation called umami. The
      umami sensation is potentiated by the presence of 5'-ribonucleotides such as
      guanosine 5'-monophosphate (5'-GMP). We have used giga-seal whole cell recording
      to examine glutamate transduction in individual cells of isolated rat fungiform
      taste buds. Approximately 56% of fungiform taste cells responded to bath
      application of glutamate. Three types of responses occurred: decrease in inward
      holding current; increase in inward holding current; and a biphasic response,
      with an increase followed by a decrease in holding current. Similar responses
      were observed in response to 5'-GMP. Further, responses to 5'-GMP may occur in
      cells that are glutamate-insensitive, suggesting that different receptors mediate
      the transduction of glutamate and 5'-GMP. Simultaneous bath application of
      glutamate and 5'-GMP resulted in a synergistic response in some taste cells.

PMID- 9929634
TI  - Development and genetics of glutamate taste preference.
AB  - The sodium salt of glutamic acid, monosodium glutamate (MSG), and certain other
      amino acids and ribonucleotides impart a unique taste sensation often called
      'umami.' We have been studying preference for umami substances in two systems:
      inbred mice and human infants. In 48-hr tests, C57BL/6J (C57) mice exhibit a
      lower preference threshold for MSG than do 129/J mice. Moreover, C57 mice show a
      greater preference across a wide range of concentrations and, at high (e.g., 300
      600 mM) concentrations, consume greater amounts of MSG. To examine whether the
      strain difference in MSG preference might be related to a similar strain
      difference in preference for sucrose and other sweeteners, as might be suggested
      from studies with rats, preferences for MSG and sucrose in the second (F2)
      generation were examined. Preferences for sucrose and for MSG were not positively
      correlated in the F2 indicating that these strain differences depend on different
      genes. For human adults, unlike mice, the taste of aqueous MSG is not palatable.
      Our studies of human infants also indicate that MSG alone is not preferred to
      plain water, but, when it is added to soup, the soup plus MSG is preferred to
      soup alone. Ongoing studies are designed to determine whether simple mixtures of
      MSG with other tastants, in particular NaCl, are preferred to water alone, NaCl
      alone, and MSG alone.

PMID- 9929635
TI  - Hypothalamic control of amino acid appetite.
AB  - Preference for umami taste materials, such as monosodium L-glutamate (MSG) and
      the 5'-ribonucleotides, inosine 5'-monophosphate (IMP) and guanosine 5'
      monophosphate (GMP), varies as a consequence of protein nutrition. Rats fed diets
      deficient in dietary protein or an essential L-amino acid (AA), L-lysine (Lys),
      avidly consumed Lys, glycine and NaCl but not umami substances. However, when the
      rats' protein nutrition was normal or when they were recovering from deficiency,
      a preference for umami substances was evident. These data suggest that the
      central mechanism for recognition of protein malnutrition may be coupled with
      umami taste preference. To test this, Lys-deficient and normal rats were employed
      as a model for taste preference changes. AA levels in plasma and brain remain
      essentially unchanged throughout the day while the rat is on standard chow but
      are altered during Lys deficiency. The recognition site for the deficit in the
      rats' brains was localized to the ventromedial (VMH) and lateral (LHA)
      hypothalamus as determined by functional magnetic resonance imaging (fMRI, 4.7
      Telsa). Studies of single neuron activity in the LHA of Lys-deficient rats
      suggested that neuronal plasticity occurred. Following Lys deficiency, cells
      responded specifically to Lys, both iontophoretically applied and during
      ingestion of AA. Other LHA neurons of nondeficient rats differentially responded
      to MSG. The present results suggest that the LHA and probably the VMH play
      important roles in recognition of deficient nutrients. Neural plasticity of
      hypothalamic cells helps maintain AA homeostasis. Furthermore, a preference for
      umami substances may be an indicator that the organism (rat or human) is free of
      protein malnutrition.

PMID- 9929637
TI  - Effects of monosodium glutamate on human food palatability.
AB  - Monosodium glutamate (MSG) is a well-known flavor enhancer used in both Western
      and Eastern cuisines. Responsible for the 'umami' (delicious) taste, it is
      incorporated into a large number of solid and liquid savory foods. Experimental
      studies have established that the presence of added MSG in foods influences
      palatability, preference and selection. Sensory evaluation tests have shown that
      both traditional and novel foods get higher palatability ratings if MSG is added
      at an appropriate dose. In young adults, behavioral tests have shown that the
      acquisition of a liking for novel foods is facilitated by the addition of MSG to
      the recipe. In institutionalized elderly persons as well as hospitalized diabetic
      patients, the addition of MSG to target foods in a lunch meal induced an
      increased intake for those specific foods, with a subsequent decreased intake of
      foods presented later in the meal. In both populations, only prandial food
      selection was affected by MSG, but meal size (kJoules) remained the same.
      Experiencing the positive effects of MSG is thus possible without inducing
      hyperphagia. In conclusion, MSG can be used casually by the consumer in order to
      increase palatability, and it can also be used selectively by nutrition experts
      in order to orient food selection toward a healthy diet composition.

PMID- 9929636
TI  - The neurophysiology of taste and olfaction in primates, and umami flavor.
AB  - To investigate the neural encoding of glutamate (umami) taste in the primate,
      recordings were made from taste responsive neurons in the cortical taste areas in
      macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste
      area. First, it was shown that there is a representation of the taste of
      glutamate which is separate from the representation of the other prototypical
      tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second,
      it was shown that single neurons that had their best responses to sodium
      glutamate also had good responses to glutamic acid. Third, it was shown that the
      responses of these neurons to the nucleotide umami tastant inosine 5'
      monophosphate were more correlated with their responses to monosodium glutamate
      than to any prototypical tastant. Fourth, concentration response curves showed
      that concentrations of monosodium glutamate as low as 0.001 M were just above
      threshold for some of these neurons. Fifth, some neurons in the orbitofrontal
      region, which responded to monosodium glutamate and other food tastes, decreased
      their responses after feeding with monosodium glutamate to behavioral satiety,
      revealing a mechanism of satiety. In some cases this reduction was sensory
      specific. Sixth, it was shown in psychophysical experiments in humans that the
      flavor of umami is strongest with a combination of corresponding taste and
      olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is
      proposed that part of the way in which glutamate works as a flavor enhancer is by
      acting in combination with corresponding food odors. The appropriate associations
      between the odor and the glutamate taste may be learned at least in part by
      olfactory to taste association learning in the primate orbitofrontal cortex.

PMID- 9929638
TI  - Excitatory and inhibitory modulation of taste responses in the hamster brainstem.
AB  - The rostral portion of the nucleus of the solitary tract (NST) contains second
      order gustatory neurons, sends projections to the parabrachial complex and
      brainstem reticular formation, and receives descending projections from several
      nuclei of the ascending gustatory pathway. Electrophysiological responses of NST
      neurons can be modulated by several factors, including blood glucose and insulin
      levels and taste aversion conditioning. We are using extracellular
      electrophysiological recording in vivo, combined with local microinjection of
      neurotransmitter agonists and antagonists, to study the mechanisms by which taste
      responses of cells in the hamster NST can be modulated. Afferent fibers of the
      chorda tympani (CT) nerve make excitatory synaptic contact with NST neurons; this
      excitation is probably mediated by the excitatory amino acid glutamate.
      Microinjection of kynurenic acid, a nonspecific glutamate receptor antagonist,
      into the NST completely and reversibly blocks afferent input from the CT nerve,
      produced by either anodal electrical or chemical stimulation of the anterior
      tongue. The non-NMDA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA)/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione
      (CNQX) also completely blocks gustatory input to these cells, whereas the N
      methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV)
      produces only a small effect. There are many gamma-aminobutyric acid (GABA)
      containing neurons within the NST and taste-responsive NST cells are maintained
      under a tonic GABAergic inhibition. Microinjection of the GABAA receptor
      antagonist bicuculline methiodide increases the taste responsiveness of NST
      neurons, whereas application of GABA inhibits taste responses in these cells.
      Preliminary data show that GABAergic inhibition can be produced by stimulation of
      the gustatory cortex. There are both intrinsic substance P (SP)-containing
      neurons and extrinsic SP-immunoreactive fibers in the rostral NST. Microinjection
      of SP into the NST enhances the responses of many NST cells to gustatory
      stimulation; NaCl-best neurons are preferentially excited by SP.

PMID- 9929639
TI  - Glutamate and synaptic plasticity at mammalian primary olfactory synapses.
AB  - Glutamate is the transmitter at synapses from the olfactory nerve (ON) to mitral
      (Mi)/tufted cells, but very little is known about the functional properties of
      this synapse. This report summarizes in vitro physiological and computational
      modeling studies investigating glutamatergic neurotransmission at ON-->Mi cell
      synapses. Single ON shocks in rat main olfactory bulb (MOB) slices elicit
      distinct early and late spiking components triggered, respectively, by (RS)-alpha
      amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainic acid (KA) and N
      methyl-D-aspartate (NMDA) receptor activation. Modeling simulations showed that
      the placement of both AMPA/KA and NMDA receptors on Mi apical dendrites
      replicates the experimentally observed early and late Mi spiking responses to ON
      shocks. Brief, tetanic ON stimulation in vitro induced robust, selective long
      term potentiation (LTP) of NMDA receptor-dependent spiking. Modeling experiments
      disclosed several potential mechanisms underlying the selective LTP of NMDA
      receptor-dependent spiking. These findings demonstrate that ON-->Mi cell
      transmission exhibits a novel form of plasticity whereby high frequency synaptic
      activity induces selective LTP of NMDA receptor-dependent spiking.

PMID- 9929640
TI  - Neural circuits for taste. Excitation, inhibition, and synaptic plasticity in the
      rostral gustatory zone of the nucleus of the solitary tract.
AB  - The rostral nucleus of the solitary tract (rNST) plays a key role in modulating,
      organizing and distributing the sensory information arriving at the central
      nervous system from gustatory receptors. However, except for some anatomical
      studies of rNST synapses, the neural circuits responsible for this first stage in
      synaptic processing of taste information are largely unknown. Over the past few
      years we have used an in vitro brain slice preparation of the rNST to study
      synaptic processing, and it has become apparent that the rNST is a very complex
      neural relay. Synaptic potentials recorded in rNST neurons resulting from
      stimulation of afferent taste fibers are a composite of excitatory and inhibitory
      post synaptic potentials. Pure excitatory postsynaptic potentials (EPSP) can be
      isolated by using gamma-aminobutyric acid type A (GABAA) receptor blockers to
      eliminate the inhibitory postsynaptic potentials (IPSP). Application of glutamate
      ionotropic receptor blockers effectively eliminates all postsynaptic activity,
      indicating that glutamate is the transmitter at the first central synapse in the
      taste pathway. Stimulation of the afferent taste fibers originating from the
      anterior (chorda tympani) and posterior (glossopharyngeal) tongue results in a
      postsynaptic potential that is a complex sum of the two individual potentials.
      Thus, rNST neurons receive convergent synaptic input from the anterior and
      posterior tongue. The IPSP component of the synaptic potentials in rNST results
      from stimulation of interneurons. If these IPSPs are initiated by tetanic
      stimulation they undergo both short-term and long-term changes. Short-term
      changes result in the development of biphasic depolarizing IPSPs, and long-term
      changes result in potentiation of the IPSPs that can last over an hr in some
      neurons. This remarkable synaptic plasticity may be involved in the mechanism of
      learned taste behaviors. Synaptic transmission in rNST consists of excitation
      combined with inhibition. The inhibition does not simply depress excitation but
      probably serves many roles such as shaping and limiting excitation, coordinating
      the timing of synaptic events and participating in synaptic plasticity. Knowledge
      of these synaptic mechanisms is essential to understanding how the rNST processes
      taste information.

PMID- 9929642
TI  - Differential distribution of amygdaloid input across rostral solitary nucleus
      subdivisions in rat.
AB  - The orosensory nucleus of the solitary tract (NST) receives input from the
      amygdala, a key node in the forebrain feeding-related network. Despite numerous
      studies documenting the existence of this pathway, however, too little is known
      about the input organization to the gustatory brainstem to allow definitive
      conclusions about its functional role. Therefore, towards the long-term goal of
      characterizing such descending regulatory pathways, the purpose of the present
      study was to describe the distribution of input arising from the amygdala. The
      anterograde tracer, biotinylated dextran, was injected into the central amygdala
      based on stereotaxic coordinates in seven adult male rats. Following a 2-week
      survival time, the animals were sacrificed. Transverse sections of the brains
      were processed to visualize transported tracer and NST anatomical topography.
      Labeled fibers were differentially distributed among subdivisions throughout the
      rostrocaudal extent of NST. Within the rostral NST, the medial (M) subdivision
      had the highest density of terminal-like endings and swellings (30% of total
      density), followed by the ventral half of rostral central (vRC, 29%), ventral (V,
      25%), dorsal half of rostral central (dRC, 12%) and rostral lateral (RL, 4%). In
      conclusion, it appears that amygdalar input preferentially overlaps with NST
      subdivisions (M, V, vRC) containing neurons with local efferent projections to
      the caudal NST and reticular nuclei that are implicated in medullary reflex
      circuits, rather than with subdivisions (dRC, RL) receiving primary orosensory
      afferent input and containing neurons having ascending efferent projections to
      the parabrachial nucleus. Thus, descending feeding-related pathways may be
      positioned to act as regulatory substrates controlling the output gain of
      brainstem circuits which may serve to modulate sensorimotor and autonomic
      reflexes in response to ingestive behaviors.

PMID- 9929641
TI  - GABAergic mechanisms that shape the temporal response to odors in moth olfactory
      projection neurons.
AB  - Mitral/tufted cells in the olfactory bulb and projection neurons (PNs) in the
      insect antennal lobe are involved in complex synaptic interactions with
      inhibitory interneurons to help shape their odor-evoked responses. In the moth
      Manduca sexta, both gamma-aminobutyric acid (GABA) and the GABAA receptor agonist
      muscimol hyperpolarize and lower input resistance in many PNs, often blocking
      ongoing spike traffic. The GABA response mimics a short-latency, chloride
      mediated inhibitory postsynaptic potential (IPSP) evoked in PNs by electrical or
      odor stimulation of afferent inputs, and the classical GABAA receptor antagonist
      bicuculline methiodide (BMI) quickly and reversibly blocks this IPSP. Focal
      injection of BMI (100 microM) immediately preceding a GABA pulse blocks the
      hyperpolarization evoked by GABA, but a similar injection of BMI preceding an
      acetylcholine (ACh) pulse fails to block the depolarization evoked by ACh.
      Moreover, the temporal pattern of odor-evoked activity in moth PNs is also
      strongly and reversibly altered by BMI. Importantly, the temporal pattern of the
      response depends on the temporal characteristics of the stimulus: continuous
      stimulation evokes more complex, rhythmic responses, whereas a pulsatile stimulus
      can be copied with a discrete burst of spikes for each pulse. Collectively our
      results indicate that PNs in the moth antennal lobe possess GABA receptors that
      share certain characteristics in common with vertebrate GABAA receptors. These
      receptors are largely responsible for helping PNs integrate information about
      both the molecular features and the timing of olfactory input to the brain.

PMID- 9929643
TI  - Ionic mechanism of GABAA biphasic synaptic potentials in gustatory nucleus of the
      solitary tract.
AB  - Gamma-aminobutyric acid (GABA) is the principal neurotransmitter of synaptic
      inhibition in the gustatory nucleus of the solitary tract (rNST). High-frequency
      activation of GABA neurons in the rNST results in biphasic inhibitory
      postsynaptic potentials (IPSPs) that are initially hyperpolarizing but then
      became depolarizing. Our results indicate that high-frequency stimulation evokes
      redistribution of Cl- and K+ ions that shifts IPSP reversal potential in a more
      positive direction, which produces a biphasic or depolarizing IPSP.

PMID- 9929644
TI  - Complex functional attributes of amygdaloid gustatory neurons in the rhesus
      monkey.
AB  - To reveal specific functions of glucose-sensitive (GS) and glucose-insensitive
      (GIS) cells in chemical information processing, single neuron activity was
      recorded in the amygdaloid body (AMY) of macaques during: 1) gustatory
      stimulations and 2) micro-electrophoretic administration of chemicals. Of the 629
      neurons tested, 56 (8.9%) responded to, usually two or more, taste qualities.
      Hedonically distinct tastants usually elicited opposite firing rate changes of
      the gustatory cells. Seventy percent of the gustatory responses were recorded
      from GS neurons (17% of all AMY cells). Catecholamines (CAs) induced discharge
      rate changes in a majority of taste-responsive neurons: The GS gustatory cells
      were suppressed by norepinephrine (in the form of noradrenaline HCl, NA), whereas
      the GIS taste-responsive neurons were facilitated by dopamine (DA). Furthermore,
      NA- and/or DA-antagonists were able to attenuate or suppress taste-elicited
      responses of several of these cells. These and previous data indicate a specific
      functional organization of AMY gustatory cells: The GS and GIS taste neurons
      appear to be involved in differential integration of feeding-associated humoral
      metabolic, motivational and exogenous chemical information.

PMID- 9929645
TI  - Temporal process from receptors to higher brain in taste detection studied by
      gustatory-evoked magnetic fields and reaction times.
AB  - Using magnetoencephalography (MEG) and a taste stimulator with rapid-rise time,
      we previously located the primary gustatory area in the human cerebral cortex and
      also investigated the relation between the onset latency of the gustatory-evoked
      magnetic fields (GEM) and reaction times (RT) in different taste qualities. In
      the present study, we investigated the temporal process from receptors to the
      higher brain in taste detection based on the results of the GEM and RT of
      different tastes. We used 100 mM, 300 mM and 1 M NaCl and 3 mM saccharine. The
      duration of each stimulus was 400 ms. The interstimulus interval was
      approximately 30 s. The temperature of both taste solution and deionized water
      was maintained the same as that of the tongue. Four subjects participated in this
      experiment. The 64-channel whole-head SQUID system (CTF Systems Inc., Canada) was
      used to measure GEM. The sampling rate was 250 Hz, and the low-pass filter was 40
      Hz. In each subject, GEM and RT to a given taste were measured separately by
      applying 40 trials of stimulation. After each trial of both measurements,
      subjects showed a perceived intensity by using their fingers. In the GEM study,
      the trials contaminated with eye movements were rejected and the remaining trials
      were averaged. Averaged GEM were super-imposed on the same sheet with all 64
      channels to measure the onset latency of GEM from the stimulus onset. RT and
      onset latencies of GEM were longer for saccharine than NaCl, and the value of RT
      minus the onset latency of GEM from RT, presumably indicating the time for higher
      brain process plus motor process, did not differ between 3 mM saccharine and 1 M
      NaCl. With increased concentrations of NaCl, RT became shorter, but onset
      latencies of GEM remained constant. Sweet taste took a longer time than salty
      taste at receptor process including the time for diffusion to receptors.

PMID- 9929646
TI  - Electrophysiological responses to bitter stimuli in primate cortex.
AB  - Studies investigating fine details of gustatory coding in the domain of each
      basic taste quality have been completed for sweet, salt, and sour stimuli. In the
      present experiment, we used chemicals that humans describe as predominantly
      bitter. We recorded the activity of 50 taste neurons in insular cortex of two
      cynomolgus macaques. Stimuli were water, fruit juice, glucose, NaCl, HCl, and 16
      bitter solutions. In a multidimensional taste space the 16 bitter stimuli formed
      a coherent cluster composed of three main subgroups: (1) QHCl, phenylalanine,
      theophylline, caffeine, propyl-thiouracil (PROP), and phenylthiocarbamide (PTC),
      all of which humans describe as rather purely bitter, (2) MgCl2, CaCl2, NH4Cl,
      and arginine, which humans describe as salty-bitter, and (3) urea, cysteine, and
      vitamin B1, which are described as sour-bitter. Vitamin B2, histidine and
      nicotine were in the center of the bitter cluster. Human descriptions of taste
      qualities conformed well to the presumed quality of each stimulus as inferred
      from its position in the multidimensional space (MDS), reinforcing the use of the
      macaque as a neural model for human gustation.

PMID- 9929647
TI  - Tyrosine phosphorylation downregulates a potassium current in rat olfactory bulb
      neurons and a cloned Kv1.3 channel.
AB  - We are studying the regulation of ion channels by protein tyrosine kinases (TKs)
      using olfactory bulb neurons (OBNs) and a cloned voltage-dependent potassium
      channel, Kv1.3, as models. Rat OBNs, which express Kv1.3 channels, had whole-cell
      outward currents that were suppressed by picomolar quantities of margatoxin and
      showed a slow inactivation that increased over a 10-min period. These same
      pharmacological and kinetic properties were found also in human embryonic kidney
      (HEK 293) cells transfected with rat Kv1.3 cDNA. The insulin receptor TK was
      detected in the OB by Western analysis. Exogenous application of insulin was
      found to suppress whole-cell outward current in all OBNs tested. Perfusion of the
      nonreceptor Src kinase likewise suppressed outward current. Current was not
      suppressed with heat-inactivated Src or when adenosine triphosphate (ATP) was
      excluded from the pipette solution. The membrane permeant tyrosine phosphatase
      inhibitor, pervanadate, was found to suppress current in a subset of neurons,
      implying the presence of an endogenous tyrosine kinase in these neurons. Using
      site-directed mutagenesis of six tyrosine residues contained within good
      recognition motifs for tyrosine phosphorylation, we constructed conservative Y to
      F mutations in the Kv1.3 cDNA and expressed the Kv1.3 channels in HEK 293 cells.
      We found that Tyr449 is a target for both the pervanadate- and Src-induced
      suppression of Kv1.3 current; Tyr111, 112 and 113 are also important for
      modulation by pervanadate; and Tyr137 is a target for modulation by Src. In
      summary, tyrosine phosphorylation of Kv1.3 and related channels may be involved
      in the modulation of OBN excitability.

PMID- 9929648
TI  - Mitral cells and ruffed cells. Two physiologically different types of relay
      neurons in the olfactory bulb of goldfish.
AB  - Anatomical differences characterizing mitral cells (MC) and ruffed (RC) cells
      were published 10-15 years ago by Kosaka and Hama in three teleost species
      (goldfish, catfish and sea eel). Physiological responses from the two different
      types of relay neurons were recorded extracellularly and simultaneously in the
      plexiform layer using a single tungsten microelectrode electrode (A-M systems
      5770; 10-12 MW). During interstimulus intervals MC responded with higher,
      frequently burst-like impulse rates (mean value 2.7 s-1) triggered by the
      activity of epithelial receptor neurons. The MC activity could be totally
      suppressed during anesthesia of the epithelium. RC impulse rates were low (mean
      value 0.75 s-1), and each potential triggered a long-lasting (3-5 ms),
      continuously variable, summed granule cells (GC) potential (approximately 3 ms
      peak to peak). MC activity via GC laterally inhibited RC potentials. In contrast
      to MC, blockade of epithelial receptor cells increased the activity of RC. During
      olfactory stimulation (nonfamiliar stimuli: amyl acetate, beta-ionone, 2
      phenylethanol 10(-6) M; relevant natural stimuli: four amino acids 10(-6)-10(-10)
      M; preovulatory pheromone 17,20 beta-dihydroxy-4-pregnen-3-one 10(-9)-10(-13) M,
      bile acid taurolithocholic acid, 10(-6)-10(-10) M) contrasting interactions
      between MC and RC were present that even in the lowest concentration resulted in
      a drastic intensification of centrally transmitted information. More frequently
      an inhibition was recorded from MC, and decreasing lateral inhibition via GC
      resulted in an activation of RC. Activation of RC resulted in an activation of
      pools of GC via initial pedunculate protrusions from the long unmyelinated
      portion of their axons, laterally inhibiting pools of MC in their vicinity.

PMID- 9929649
TI  - fMRI study of taste cortical areas in humans.
AB  - We used 3 Tesla functional magnetic resonance imaging (fMRI) with echo planar
      imaging to map taste projections in the human. Activations were found surrounding
      and buried in the sylvian fissure; the upper part of insula, the frontal
      operculum, and the foot of the pre- and postcentral gyri were usually activated.
      Moreover, we could describe, for the first time, a lateralized associative
      projection located in the lower part of the dominant hemisphere of the subject (n
      = 10). We also observed activations in the anterior cingulate gyrus, the
      centromedial thalamus, and other areas related to emotional or cognitive
      processes. Thirty subjects were submitted to a familiarization experiment
      sampling neophobic and nonneophobic stimuli. Measurements of isointense
      concentrations, magnitude estimates and hedonic values were assessed repetitively
      for 10 weeks. Five subjects performed 3 fMRI experiments, before, during and
      after familiarization. Psychophysical data showed a relationship between the
      evolution of the hedonic assessment and the intensity of the perception, and fMRI
      results showed a relationship between the evolution of the hedonic assessment and
      the evolution of the percent of activated pixels in taste cortical area.

PMID- 9929650
TI  - Olfactory bulb and tract and temporal lobe volumes. Normative data across
      decades.
AB  - The sense of smell shows a diminution with age as measured by the University of
      Pennsylvania Smell Identification Test (UPSIT). To ascertain whether the volumes
      of the olfactory bulbs and tracts (OBTs) and the temporal lobes (TL) declined in
      parallel to smell function, we examined 36 individuals from ages 22 to 78 who did
      not complain of any loss of the sense of smell using magnetic resonance (MR)
      imaging. The OBT volumes showed an initial increase to the 4th decade of life and
      then a decrease with increasing age, while the trend in TL volume was not as
      dramatic. There was no correlation between OBT or TL volumes with unilateral or
      total UPSIT scores. The normative data by decades can be used to assess the OBTs
      of cohorts of patients with neurodegenerative disorders that affect olfaction.

PMID- 9929651
TI  - Understanding neural interactions in learning and memory using functional
      neuroimaging.
AB  - Neuroimaging methods such as positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI) provide a unique opportunity to explore
      activity across the entire human brain in many different behaviors. An important
      additional feature is the ability to examine interacting neural systems using
      methods that focus on the covariances of activity. Two of these methods, partial
      least squares and structural equation modeling, are presented with specific
      examples. Shifting prefrontal and limbic interactions were observed in a working
      memory task for faces. In an episodic memory retrieval study, the activity of
      right prefrontal cortex was related to either memory search or successful
      retrieval depending on its interactions with other brain regions. This latter
      observation implies that regional activity must be evaluated within the neural
      context in which it occurs. The general hypothesis that learning and memory are
      emergent properties of network interactions is discussed, emphasizing that a
      region can play a different role across many functions and that role is governed
      by its interactions with anatomically related regions.

PMID- 9929652
TI  - Human brain function during odor encoding and recognition. A PET activation
      study.
AB  - In previous positron emission tomography (PET) studies we have shown significant
      regional cerebral blood flow (rCBF) increases during olfactory stimulation:
      unilaterally in the right orbitofrontal cortex, and bilaterally in the inferior
      frontal and temporal lobes (piriform cortex). In the present study we
      investigated brain function during different stages of olfactory memory
      processing. Subjects were scanned during four tasks: odor encoding, long-term
      odor recognition, short-term odor recognition and a no-odor sensorimotor control
      task. Subjects were 12 right-handed healthy volunteers (6 men, 6 women). Each
      subject underwent a training session four days prior to their PET scan to learn
      the six odors required for the long-term memory scan. PET scans were obtained
      with a Siemens Exact ECAT HR+ 3D system using H2(15)O methodology and 60-sec
      scanning intervals. PET images were coregistered with each subject's magnetic
      resonance imaging scan, averaged, and transformed into standard stereotaxic
      space. Paired image subtractions were analyzed for rCBF changes. Preliminary
      analyses have revealed significant activation of the right orbitofrontal region
      and bilateral piriform cortices during the long-term odor recognition task
      compared with the control task. Activation of the right piriform cortex was
      present during the short-term recognition task. Brain activity during encoding
      and retrieval tasks also involved prefrontal cortices. PET activation studies of
      memory in other modalities have led to hypotheses of a hemispheric
      encoding/retrieval asymmetry in frontal cortex; the generalizability of this
      theory to olfactory memory will be discussed.

PMID- 9929653
TI  - Functional lateralization of human gustatory cortex related to handedness
      disclosed by fMRI study.
AB  - Ten healthy subjects aged 20-25 including five right-handed and five left-handed
      according to the Dellatolas test participated in this functional magnetic
      resonance imaging (fMRI) study. A 3 Tesla whole-body MR scanner allowed echo
      planar imaging (EPI)-64 x 64 pixels, repetition time (TR) = 6 s, field of view
      (FOV) = 20 x 20 cm2--associated to acute anatomical localization of activated
      foci (256 x 256 pixels). Subjects were bilaterally stimulated with NaCl 85 mM,
      aspartame 2 mM, quinine hydrochloride 1 mM, glycyrrhizic acid 0.5 mM, guanosine
      monophosphate 1 mM and D-threonine 250 mM alternating with water. Stimuli and
      rinse were continuously pushed as bolus of 50 microliters every 3 s to the
      subject's mouth through microsyringes. We detected brain activated areas by
      correlation of the MR signal to an on-line perception profile recorded for each
      experiment and each subject with the finger-span method. We found most
      activations in the insula and the perisylvian region in agreement with previous
      electrophysiological studies on monkeys and clinical reports in humans. The
      superior part of the insula was bilaterally activated, in accordance with a whole
      mouth stimulation. A striking lateralization related to handedness was found in a
      lower part of the insula. This projection in the dominant hemisphere, located in
      the same coronal plane as the upper insular activation, is the first evidence of
      a functional lateralization of brain processing involved in taste perception.

PMID- 9929654
TI  - Ipsilateral dominance of human olfactory activated centers estimated from event
      related magnetic fields measured by 122-channel whole-head neuromagnetometer
      using odorant stimuli synchronized with respirations.
AB  - The aim of this study was to measure and analyze olfactory event-related magnetic
      fields using a whole-cortex biomagnetometer (122-channel SQUID gradiometer). Amyl
      acetate gas (approx. 1%) was administered for 300 msec into either the right or
      left nostril in synchronization with respiration using a mask and an optical
      fiber sensor. Clear olfactory event-related magnetic fields were asymmetrically
      obtained on both sides of the forehead in all six subjects. The generators of
      olfactory magnetic fields were estimated at two regions located fairly
      asymmetrivally near the bilateral frontal deep areas. The goodness-of-fit was
      better for the two-dipole model than the one-dipole model in all experiments. In
      almost all subjects the latency and intensity of ipsilateral olfactory
      magnetoencephalography (MEG) responses were shorter and larger than those of the
      contralateral responses, respectively. These results suggest that the olfactory
      MEG responses on the ipsilateral side are generally larger and more dominant than
      those on the contralateral side in the human olfactory system.

PMID- 9929655
TI  - Chemosensory alteration of information processing.
AB  - Previous research has found both facilitation and interference when odors are
      administered during the performance of cognitive tasks. The present research was
      designed to investigate the possibility that odors might differentially effect
      different varieties of cognitive tasks. Twelve subjects performed matched verbal,
      numeric, and spatial tasks as event-related potentials were measured. Odors and
      tones were introduced as subjects completed the tasks in a paradigm optimized to
      produce disruption of performance. Results indicated that P300 amplitude to the
      task stimuli depended upon the type of task and the modality of the distractor.
      P300 amplitude was relatively consistent across tasks for the tone distractor.
      During the olfactory distractor, P300 amplitude was greater for the symbolic
      stimuli (verbal and numeric) and lower for the spatial. Reaction times to the
      various tasks did not differ as a function of the modality of the distractor.

PMID- 9929656
TI  - Age effects on central nervous system activity reflected in the olfactory event
      related potential. Evidence for decline in middle age.
AB  - A series of studies in this laboratory using the olfactory event-related
      potential (OERP) have examined the underlying central nervous system activity
      associated with age-related changes in olfactory functioning. Early (sensory)
      components of the OERP showed reduced amplitude and longer latency in elderly
      subjects, with larger effects in males. Amplitudes are already decreased in
      middle age. The late cognitive component, P3, showed a longer latency as well as
      a decreased amplitude in the elderly, with effect sizes for age significantly
      larger for the late component than for the early components. We report here the
      significantly longer latency, particularly for the P3, in middle-aged persons,
      suggesting age-related slowing of olfactory information processing as early as
      the 50s. Results suggest that the elderly brain, and indeed, the middle-aged
      brain shows smaller responses to odors, is less able to allocate attentional
      resources and slows in its olfactory cognitive processing. The OERP is a potent
      reflection of these changes.

PMID- 9929657
TI  - Olfactory evoked responses and identification tests in neurological disease.
AB  - To assess the value of smell testing we used olfactory evoked potentials (OEP)
      and an identification test in multiple sclerosis, Parkinson's disease, motor
      neuron disease and Alzheimer's disease. METHODS: The OEP to H2S (20 ppm) was
      obtained using an olfactometer designed to stimulate olfactory nerve endings
      only. Odor recognition was assessed by the University of Pennsylvania Smell
      Identification Test (UPSIT). In all instances the disease was 'definite' based on
      standard diagnostic criteria. Controls were derived from 156 healthy people.
      RESULTS: 1) Multiple Sclerosis: 11/72 patients (15%) were abnormal on UPSIT. For
      OEP there was significant increase of latency and decrease in amplitude in 6/26
      patients (23%). 2) Parkinson's Disease: 126/155 (81%) patients had an abnormal
      UPSIT score. 12/37 (32%) had prolonged latency with normal amplitude measurement
      on OEP, but 27 had absent or unclear readings. 4/10 with normal UPSIT displayed
      abnormality on OEP. 3) Motor Neuron Disease: 9/58 (16%) were abnormal on UPSIT.
      There was significant delay in 1/10 (10%) patients on OEP. 4) Alzheimer's
      Disease: UPSIT scores were abnormal in all 8 patients examined. OEP was normal in
      4 of these who could be tested. CONCLUSION: Smell dysfunction was found in all 4
      conditions but most severely in Parkinson's Disease (over 80%). The UPSIT in
      general showed abnormality more frequently than OEP. The olfactory defect
      probably involves peripheral structures in all diseases tested except
      Alzheimer's. A patient with normal olfaction is unlikely to have idiopathic
      Parkinson's disease.

PMID- 9929658
TI  - Olfactory function in acute rhinitis.
AB  - This study was performed to investigate the effects of the common cold on
      olfactory function, which was assessed using chemosensory event-related
      potentials (CSERP, in response to both olfactory [H2S] and trigeminal [CO2]
      stimuli) and psychophysical measures (intensity ratings, odor discrimination,
      butanol threshold); nasal volume was assessed by means of acoustic rhinometry.
      The investigation was performed in 36 subjects (18 women, 18 men). After onset of
      the rhinitis (day 0) measurements were performed on days 2, 4, 6 and 35. The cold
      produced a decrease of the volume of the anterior nasal cavity accompanied by an
      increase of mucus secretion, an increase of olfactory thresholds, a decrease of
      intensity ratings and a decrease of N1 CSERP amplitudes to olfactory and
      trigeminal stimuli. When mucus secretion of the contralateral nasal cavity was
      controlled with oxymetazoline, N1 amplitudes to olfactory stimuli were still
      affected by the cold as indicated by the significant increase of amplitudes as
      subjects recovered; this phenomenenon was not found for responses to trigeminal
      stimuli. This indicates that the common cold has a small effect on olfactory
      function which may be independent of nasal congestion.

PMID- 9929659
TI  - Steady state visual evoked potential (SSVEP) changes in response to olfactory
      stimulation.
AB  - The location, nature and characteristics of brain activity during detection and
      identification of odors are of importance if brain function techniques are to be
      of value to sensory systems. Steady state probe topography (SSPT) has been used
      in our laboratory to record steady state visual evoked potentials (SSVEP), which
      have demonstrated cognitive task-related changes in a variety of testing
      paradigms. The enhanced spatial (when using 64 channels) and temporal resolution
      (380 ms) of the system enable the brain electrical activity changes occurring
      before, during and after delivery of an odor to be examined. We have developed a
      system which can deliver odors during normal respiration and the accurate timing
      needed for SSVEP recordings. The system is based on the premise that a subject
      breathing butanol compared with filtered medical air will demonstrate SSVEP
      topographic changes associated with detection and identification of butanol.
      During our experiments the subject has either an air sample or an equal volume of
      butanol injected into the inspiratory airflow. These are randomized, and every
      breath has the same stimulus system with no known clues as to the differences
      apart from detection. The results from a panel of 10 female subjects--who all
      identified the butanol correctly--showed that butanol delivery resulted in
      sequences of changes in SSVEP topography (amplitude and latencies) which involved
      parietal, frontal and temporal regions. While consistent with other studies
      (parietal changes), our results revealed more dynamic temporal changes involving
      prefrontal and parietal regions at different periods around odor delivery.

PMID- 9929660
TI  - Central nervous correlates of chemical communication in humans.
AB  - The recording of chemosensory event-related potentials (CSERPs) has been
      established as an objective method in the assessment of central odor processing
      in humans. In the present study CSERPs were used to investigate whether human
      body odor is genetically determined by the major histocompatibility complex
      (MHC), referred to in humans as the human leukocyte antigen (HLA). The
      immunological function of the MHC is the discrimination of self/nonself within
      the immune system. In rodents it has been shown that body odor is significantly
      influenced by the MHC and that it can be discriminated by members of different
      species. To create a sufficiently large subject pool, 144 subjects were screened
      for their HLA class I loci A and B. During the electroencephalography (EEG)
      session the subjects (n = 40/20 women) were confronted with the body odor
      (axillary hair) of three different donors. Two donors (d1 and d2) were HLA
      similar but had a different HLA type than the third donor (d3) and the perceiving
      subject. The third donor and the perceiver shared a similar HLA type. Half of the
      perceivers received odors from donors of the same sex, the other half smelt odors
      from donors of the opposite sex. In the EEG session subjects were presented with
      200 trials. The odors were delivered through a constant flow olfactometer non
      synchronously to breathing. The odor of d1 appeared frequently (p = 0.6) whereas
      the odors of d2 and d3 appeared each at a rate of p = 0.2. During half the trials
      the subjects were instructed to respond to the odor of d2, during the other half
      to the odor of d3. The EEG was recorded from Fz, Cz, Pz, F3, P3, F4 and P4 in
      reference to linked mastoids. First results show that male perceivers show
      enhanced potentials in response to male donors of a similar HLA type (d3). The
      CSERP results of the other groups as well as valence and attractiveness ratings
      will be discussed.

PMID- 9929661
TI  - Developmental effects on odor learning and memory in children.
AB  - The child version of the California Odor Learning Test (COLT) was designed to
      assess cognitive functioning in impaired and healthy children. The COLT's
      rationale was based on two assumptions. First, measures of cognitive functioning
      are a good index of severity or extent of brain damage if compared between normal
      and clinical populations. Second, the cognitive-mediated tasks of verbal odor
      recall, recognition and identification were suitable to evaluate cognitive
      functioning. The focus of this study was to determine the COLT's ability to
      detect developmental differences in odor learning and memory. The participants
      were 51 healthy children who were twice administered the COLT with a weekly delay
      between tests. They were ascribed to two age-groups (7-10 and 11-15 years old)
      according to levels of cognitive development. The COLT employed 22 common odors
      and included two sessions. In the first session, children learned two sets of six
      odors. The first set was presented three times, the second one once, during a
      single learning episode. Following learning, children recalled the odors of the
      first set by name at free recall and category-cued recall. The second session
      included the following tasks: long-term free odor recall and category-cued odor
      recall, odor recognition-memory and verbal odor identification. A series of
      analyses of variance (ANOVAs, p < 0.05) with age as between-subject variable and
      repeated measurements on recall revealed significant differences between the two
      groups on the number of odors correctly recalled by name both at free recall,
      category-cued recall, recognition and identification. There were differences in
      false alarms at odor recognition between the two groups. Children from both
      groups benefited from a learning effect over odor trials. A gender effect was
      found for odor free recall at retest. These results suggest that the COLT has the
      potential to serve as a useful tool in the assessment of cognitive functioning in
      children.

PMID- 9929662
TI  - Phonological and perceptual components of short-term memory for odors.
AB  - Just as a written word can be encoded and retained in memory either verbally or
      in a visual form, so it might seem that an odor might be retained as either a
      verbal description/name or as a perceptual (olfactory) code. However, one view
      has it that olfactory memory in the short term does not exist as a separate
      perceptual code. This was examined in an experimental paradigm in which errors in
      memory could be recognized as deriving from the substitution of similar verbal
      codes or of similar olfactory codes. The set of odorants presented for recall was
      divided into three groups: (i) base odorants (odorants that might be replaced in
      memory either by similar verbal or similar olfactory representations); (ii)
      verbal foils (stimuli dissimilar to the base stimuli in odor but which is similar
      in name); and (iii) odor foils (the reverse). The substitution errors made when
      attempting to recall test odorants were classified as verbal errors or olfactory
      errors. A substantial proportion of the errors were olfactory, but verbal errors
      also occurred. These results support the presence of short-term perceptual
      olfactory memory, rather than simply verbal encoding of olfactory perceptions.

PMID- 9929663
TI  - Metrics of odorant dissimilarity. Labeled magnitude scale vs magnitude
      estimation.
AB  - Magnitude estimation (ME) has long been the standard rating tool for stimulus
      intensity because of the simplicity and generalizability of the resultant power
      function relationships. However, the choice of a scaling procedure for rating
      complex stimuli (odorant) dissimilarity must be based on a different set of
      criteria due to an inability to evaluate relationships against a physical
      continuum. Recently, chemosensory labeled magnitude scales (LMS) have been
      developed, which produce ratings with many of the same properties as ME. The
      current study sought compare LMS to ME as metrics for describing the magnitude of
      perceived odorant dissimilarity. Forty subjects rated pair-wise odorant
      dissimilarity with either a LMS or ME. Each subject evaluated two sets of
      odorants with differing ranges of dissimilarity (high contrast and low contrast)
      in order to compare the sensitivity of the two measures to possible contrast
      convergence. The ME ratings were normalized such that the two metrics produced
      equal means. The scales produced similar ratings of odorant dissimilarity (r =
      0.92) and showed small but similar effects of contrast convergence. However, the
      coefficient of variation of dissimilarities rated with ME was 2.8 times that of
      dissimilarities rated with the LMS. Subjects accepted the LMS without the usual
      anxiety that accompanies first time users of ME. LMS provide stable ratings of
      odorant dissimilarity while preserving the inferred ratio scale properties of ME.

PMID- 9929664
TI  - Spatiotemporal masking in pure olfaction.
AB  - In olfaction, it is not possible to determine which nostril is being stimulated,
      i.e., lateralize, when a pure olfactory substance, e.g., phenylethyl alcohol or
      vanillin, is administered into one nostril, and, simultaneously, an odorless,
      solvent blank into the contralateral nostril. We subjected volunteers to
      extensive training, with feedback on each trial, in an attempt to determine
      whether it was possible, in these well-trained subjects, to overcome this
      apparent impossibility. We failed to obtain any evidence to support the notion
      that a pure olfactory stimulus could be lateralized when the odorant and blank
      were presented simultaneously. The task, however, became simple when the odorant
      and the blank entered each nostril sequentially. We investigated, using a two
      channel olfactometer, temporal parameters that enabled such discrimination. We
      controlled the duration of odorant and blank air puffs, as well as their mutual
      timing, to determine the threshold stimulus onset-disparity, i.e., the interval
      between stimulus onset and blank onset, that resulted in an inability to
      lateralize. Latencies shorter than the threshold interval would be perceived as
      simultaneous stimulation. We determined that the onset interval was between 200
      and 400 ms, depending on the duration of the stimuli (a shorter interval was
      noted for stimuli of 150-ms duration relative to 300- and 450-ms stimuli). This
      was also true when two odorants were applied, rather than an odorant and a blank,
      and the subject was instructed to focus on the sequence of odorant delivery and
      side of stimulation. The temporal onset threshold was the same for lateralization
      and for order of stimulation. Whether the olfactory system per se mediates this
      discrimination or whether inputs from olfaction and chemesthesis, via trigeminal
      free nerve endings stimulated by air-stream onset, combine to allow this
      discrimination has yet to be determined.

PMID- 9929665
TI  - Focused attention and the detectability of weak gustatory stimuli. Empirical
      measurement and computer simulations.
AB  - Attentional processes can modulate the detectability of weak stimuli; for
      example, the detectability of visual or auditory signals can depend on whether
      attention is allocated to the appropriate spatial location (vision) or acoustic
      frequency (hearing). Earlier attempts in the first author's laboratory to find
      analogous effects of focused attention on the detectability of taste stimuli were
      equivocal, in part it seems because human gustatory sensitivity can fluctuate
      substantially over time, a serious problem when using procedures that track
      sensitivity (d') to a constant stimulus concentration. To circumvent this
      problem, we adopted an adaptive psychophysical procedure, the transformed up-down
      method, using a 3-down/1-up rule to determine how the threshold to detect weak
      concentrations of sucrose and citric acid depended on whether the stimulus
      presented in a given two-alternative, forced-choice trial was expected or
      unexpected. The results showed threshold sensitivity to be slightly but
      consistently poorer when the test stimulus was unexpected (e.g., sucrose
      presented when citric acid was expected) than it was when the test stimulus was
      expected (e.g., sucrose presented when sucrose was expected). In this attentional
      paradigm, the unexpected stimulus must perforce be presented on only a small
      fraction of the trials. In selecting a procedure, we chose a 3-down/1-up adaptive
      rule rather than the more popular 2-down/1-up rule, a choice that turned out to
      be in line with results of Monte Carlo computer simulations. These simulations
      suggest that across a wide range of conditions (starting stimulus concentrations,
      step sizes), the variability in threshold measurements can be smaller with a 3
      down/1-up rule than with a 2-down/1-up rule, even when the total number of trials
      is the same and not very great.

PMID- 9929666
TI  - Sensory properties of selected terpenes. Thresholds for odor, nasal pungency,
      nasal localization, and eye irritation.
AB  - We tested four normosmics and four anosmics in detection thresholds for six
      terpenes commonly found indoors: cumene, p-cymene, delta-3-carene, linalool, 1,8
      cineole and geraniol. Normosmics provided odor thresholds and anosmics provided
      nasal pungency thresholds. All subjects provided nasal localization (i.e.,
      right/left nostril) and eye irritation thresholds. Each type of threshold was
      measured eight times per subject-stimulus combination. Stimuli were presented
      from squeeze bottles in a two-alternative forced-choice procedure via an
      ascending method of limits. Odor thresholds ranged between 0.1 and 1.0 parts per
      million (ppm, by volume). Nasal pungency thresholds lay about three orders of
      magnitude above odor thresholds. Nasal localization and eye irritation thresholds
      did not differ between normosmics and anosmics, and fell close to nasal pungency
      thresholds. Olfactory thresholds could be obtained for all stimuli in all
      repetitions using the criterion of five correct choices in a row. Trigeminal
      thresholds (i.e., pungency, localization and eye irritation) could be obtained on
      all repetitions only for some terpenes using that same criterion. Carene and
      cineol produced nasal pungency and eye irritation on all repetitions. None of the
      terpenes could be localized on all repetitions, but cineol was localized a higher
      percentage of instances than were the other stimuli. At the other extreme,
      geraniol failed to evoke any of the three trigeminal responses in most instances.
      Overall, the results indicate that the three trigeminal thresholds produce a
      uniform view of the potency of these terpenes, with nasal pungency and eye
      irritation being slightly more sensitive than nasal localization. Furthermore,
      application of a previously derived linear solvation energy relationship to the
      results reinforced the view that physicochemical properties can predict the
      chemesthetic impact of volatile organic compounds.

PMID- 9929667
TI  - Draize eye scores and eye irritation thresholds in man can be combined into one
      QSAR.
AB  - Draize eye scores (DES) of 37 pure organic liquids have been converted into
      scores for the corresponding vapors, DES/P0, where P0 is the liquid vapor
      pressure in atmospheres at 298 K. It is shown that there is a constant difference
      of 6.7 between values of log(DES/P0) and log (1/EIT), where EIT is the eye
      irritation threshold in parts per million (ppm, by volume) of eight vapors for
      human subjects. The 37 log(DES/P0) values can be combined with log(1/EIT) values
      for 17 vapors into one quantitative structure-activity relationship (QSAR) for
      sensory potency (SP) using our general solvation equation, [formula: see text]
      where R2 is an excess molar refraction, pi 2H is the compound
      polarizability/dipolarity, sigma alpha 2H and sigma beta 2H are the compound
      hydrogen-bond acidity and basicity, and L16 is the gas-hexadecane partition
      coefficient at 298 K. n is the number of data points, r the correlation
      coefficient, SD the standard deviation, and F the F-statistic. LogSP is then
      either [log(DES/P0) - 0.66] or log (1/EIT), confirming the result for the eight
      common compounds. It is suggested that the equation can be used to predict eye
      irritancy of organic vapors and pure liquids. It is further suggested that for
      the compounds in the data set, the main process in eye irritation is transfer of
      the compound from the vapor or pure liquid to a biological phase, and a number of
      chemical properties of the biological phase have been mapped out through the
      equation. These properties are consistent with corresponding properties for a
      number of organic liquid phases.

PMID- 9929668
TI  - Using olfaction to study memory.
AB  - In a series of studies we have been exploring the role of hippocampal function in
      memory using the model system of olfactory-hippocampal pathways and odor learning
      in rats. Our experiments show that hippocampus itself is not essential to memory
      for single odors, but is critical for forming the representations of relations
      among odor memories, and for the expression of odor memory representations in
      novel situations. These studies that exploit the exceptional qualities of
      olfactory learning are helping to clarify the nature of higher order memory
      processes in all mammals, and extending to declarative memory in humans.

PMID- 9929669
TI  - Are odors the best cues to memory? A cross-modal comparison of associative memory
      stimuli.
AB  - To test the claim that odors are the 'best' cues to memory, several cross-modal
      experiments were conducted in which odors were compared with verbal, visual,
      tactile and musical stimuli as associated memory cues. Each experiment comprised
      two sessions (encoding and retrieval) separated by 48 hr. At the encoding
      session, a series of stimuli were incidentally associated to a set of emotionally
      arousing pictures. At the retrieval session, memory accuracy and emotionality
      were assessed. Across experiments, results revealed that odors were equivalent to
      other stimuli in their ability to elicit accurate recall, but that odor-evoked
      memories were always more emotional. Notably, emotional responses did not vary as
      a function of stimulus type at encoding. These data indicate that emotional
      saliency, rather than accuracy, is responsible for the impression that odors are
      superior reminders, and that retrieval processes (cf. encoding processes) are
      responsible for the distinctive emotionality of odor-evoked memories.

PMID- 9929670
TI  - Semantic mediation of age-related deficits in episodic recognition of common
      odors.
AB  - In the present research, the relationship between various semantic memory
      functions and episodic odor memory across the adult life span is addressed. In
      contrast to earlier evidence that odors may be encoded and stored as unique,
      nonlinguistic whole percepts, the present work suggests that episodic odor
      information is mediated by factors that can be subsumed under the rubric of
      semantic memory. Specific olfactory knowledge, such as perceived familiarity and
      identifiability, is strongly and positively related to episodic odor memory
      performance. In contrast to research using verbal and visual stimuli, proficiency
      in complex verbal intellectual abilities, such as vocabulary and fluency, seems
      to be of minor importance in memory for olfactory information. In agreement with
      earlier findings, this research indicates that episodic odor memory deteriorates
      across the adult life span. A similar negative age trend was observed for odor
      naming. Most importantly, statistical control of odor naming resulted in the
      elimination of age-related odor memory deficits. These results suggest that age
      related failures in accessing specific semantic information of odors determine
      largely age-related deficits in episodic odor recognition.

PMID- 9929671
TI  - Abnormality of semantic network in patients with Alzheimer's disease. Evidence
      from verbal, perceptual, and olfactory domains.
AB  - A series of studies was initiated to model the organization of semantic memory in
      Alzheimer's disease (AD) patients using multidimensional scaling (MDS) and
      Pathfinder analyses. The resulting models (cognitive maps or semantic networks)
      embed studied stimuli in a coordinate space or network where distances between
      points are assumed to reflect psychological proximity between items. The
      organization of semantic networks in verbal and sensory domains were modeled
      based upon the frequency of the subject's choice of two concepts as most alike.
      Results suggested that while the organization of concepts in the semantic
      networks of AD patients was primarily based upon a concrete perceptual dimension
      in both verbal and olfactory domains, those of normal controls subjects were
      predominantly organized by an abstract conceptual attribute. Also, networks of AD
      patients were more complex and chaotic than normal, that is, they consisted of
      more unnecessary connections and of atypical strengths of association between
      concepts.

PMID- 9929672
TI  - Odor memory in normal aging and Alzheimer's disease.
AB  - The ability in normal elderly to verbally recall previously presented odors and
      to learn this task across trials was studied by applying a design which compared
      performance on the California Verbal Learning Test (CVLT) with an analogous odor
      test. Results suggest that both immediate and delayed recall of odors, both free
      and cued, as well as the ability to learn across trials is impaired in normal
      aging, perhaps more so for olfaction than for audition, which can be referred to
      poor use of semantic-clustering strategies and poor identification. Olfactory
      decline in memory in normal aging is, however, far from as affected as in
      Alzheimer's disease (AD). Two studies of persons with questionable AD
      demonstrated significant deficits in both recognition memory and identification
      of odors. Although further research is required, the findings from these 'pre
      clinical' cases imply that performance on olfactory-mediated tasks may contribute
      to early diagnosis of AD.

PMID- 9929673
TI  - Differences and similarities in the perception of everyday odors. A Japanese
      German cross-cultural study.
AB  - To investigate the influence of experience on odor perception the responses of 40
      Japanese and 44 age-matched German women to everyday odorants were compared.
      Subjects were presented with six 'Japanese,' six 'European' and six
      'international' odorants and asked to rate them on intensity, familiarity,
      pleasantness and edibility, and to describe associations elicited by them, and if
      possible to name them. Significant differences were found between the two
      populations on all measures, with a close association of pleasantness ratings and
      edibility judgments suggesting the particular influence of eating habits on odor
      perception. Positive correlations between familiarity and pleasantness, strength
      of hedonic judgment and intensity, and familiarity and intensity were also found
      in both groups and for most individuals. The generality of these findings was
      supported by the results obtained from testing 40 Mexican women with the same
      odorants.

PMID- 9929674
TI  - The use of olfactory receptor neurons (ORNs) from biopsies to study changes in
      aging and neurodegenerative diseases.
AB  - A gradual loss of olfactory capability with age and in a number of
      neurodegenerative diseases is common, and mechanisms underlying these losses are
      not understood. We determined the feasibility of using ORNs obtained from
      olfactory epithelial biopsies to identify possible changes in ORN function that
      may contribute to olfactory impairment in these individuals. ORNs from nine
      healthy subjects (66-84 yr), three patients with Alzheimer's disease and one with
      multi-infarct dementia were studied with calcium imaging techniques and two
      odorant mixtures. Seventy-five viable ORNs were studied; 53% of these were
      odorant responsive, and twenty percent of these responded to both odorant
      mixtures. In contrast, 25% of 173 ORNs from younger subjects were odorant
      responsive, and none of these responded to both odorant mixtures. The proportion
      of cells responding to each of the odorant mixtures also differed between older
      and younger subjects. These studies demonstrate the feasibility of this approach
      to examine age or disease-associated changes in neuronal function. Further, age
      related changes in ORN selectivity may contribute to changes in olfactory
      performance.

PMID- 9929675
TI  - Human olfactory bulb: aging of glomeruli and mitral cells and a search for the
      accessory olfactory bulb.
AB  - The aims of this study on the human olfactory bulb were two. First morphometry of
      the bulbs revealed marked declines during aging in the numbers of mitral cells
      and glomeruli, the bulb's principal integrative and relay elements. Numbers of
      glomeruli and mitral cells in each bulb of the young adult human were found to be
      approximately 8,000 and 40,000, respectively; these numbers declined steadily
      with age at an approximate rate of 10% per decade, so that in the ninth and tenth
      decades less than 30% of these elements remain in place. Such a marked decline
      with aging is suggested to underlie in part the decline in olfactory abilities
      (odor detection and identification) of humans with aging. In a separate study a
      systematic search for presence of an accessory olfactory bulb in the adult and
      aging bulbs was undertaken. No positive evidence for such an organized formation
      was found in the various regions of the adult bulbs of different age groups. The
      implications of these negative findings for the recent theories on human
      vomeronasal function and pheromonal perception are discussed.

PMID- 9929676
TI  - Age-related changes in the prevalence of smell/taste problems among the United
      States adult population. Results of the 1994 disability supplement to the
      National Health Interview Survey (NHIS).
AB  - Information about the prevalence of disorders of the chemical senses has been
      limited. In the late 1970s, the consensus among experts convened by the National
      Institutes of Health (NIH) was that more than 2 million adults in the United
      States had a disorder of smell or taste. A large, nonrandom survey conducted by
      the National Geographic Society in 1987 found that 1% of their 1.2 million
      respondents could not smell 3 or more of 6 odorants using a 'scratch and sniff'
      test. Age was an important factor, with a decline beginning in the second decade
      of life. No comparable data have been available for taste, although it has been
      suggested that the sense of taste remains more robust with age. The National
      Institute on Deafness and Other Communication Disorders (NIDCD), NIH, began
      collaborating with the National Center for Health Statistics (NCHS) in 1993 to
      acquire information on the prevalence of smell/taste problems using the
      Disability Supplement to the National Health Interview Survey (NHIS). This survey
      was administered to approximately 42,000 randomly-selected households
      (representing about 80,000 adults over 18 years of age) in 1994. Adjusted
      national estimates derived from this survey showed a prevalence of 2.7 million
      (1.4%) U.S. adults with an olfactory problem. Also, 1.1 million (0.6%) adults
      reported a gustatory problem. When smell or taste problems were combined, 3.2
      million (1.65%) adults indicated a chronic chemosensory problem. The prevalence
      rates increased exponentially with age. Almost 40% with a chemosensory problem
      (1.5 million) were 65 years of age or greater. In a multivariate analysis, the
      individual's overall health status, other sensory impairments, functional
      limitations (including difficulty standing or bending), depression, phobia, and
      several other health-related characteristics were associated with an increase in
      the rate of chemosensory disorders.

PMID- 9929677
TI  - Very early changes in olfactory functioning due to Alzheimer's disease and the
      role of apolipoprotein E in olfaction.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative illness marked by
      memory loss and at least one other cognitive disturbance. Early diagnosis of the
      disease has proved difficult and has therefore been the focus of much research.
      Apolipoprotein E (ApoE), a protein manufactured and distributed throughout the
      body, has shown specificity of binding to the beta A4 peptide, the primary
      component in the senile plaques of AD. Furthermore, the ApoE, epsilon 4 (epsilon
      4) allele, is overrepresented in AD. These two lines of evidence suggest that
      ApoE, specifically the epsilon 4 allele, plays an important role in the
      development of AD. Further support for this hypothesis appears in
      neuropsychological data showing cognitive decrements in ostensibly nondemented
      individuals with the epsilon 4 allele, compared to those without the allele. It
      is also well known that olfaction is compromised in AD. Thus, the purpose of this
      study was twofold: (1) to examine very early changes in olfactory functioning due
      to AD and (2) to examine the role of ApoE in olfactory functioning in people at
      risk for AD by virtue of early cognitive decline. Results demonstrated changes in
      olfactory threshold the year immediately preceding change in diagnosis from
      normal control to AD. Also, in individuals with mild cognitive impairment, those
      with the ApoE epsilon 4 allele show poorer thresholds than those without the
      epsilon 4 allele.

PMID- 9929678
TI  - Effect of psychotropic drugs on taste responses in young and elderly persons.
AB  - The taste of six psychotropic drugs (amitriptyline HCl, clomipramine HCl,
      desipramine HCl, imipramine HCl, doxepin HCl, and trifluoperazine HCl) can be
      detected at concentrations of 0.1 mM or less in both young and elderly
      individuals. At concentrations 4 times higher than the detection thresholds,
      these drugs have bitter as well as other unpleasant taste properties. Oral
      exposure to these drugs not only induces a taste from the drug itself but also
      alters taste perception of other compounds such as NaCl and sucrose. These
      results indicate that both hypogeusia and dysgeusia may be induced by
      psychotropic medications.

PMID- 9929679
TI  - Apolipoprotein E and Alzheimer's disease. The tip of the susceptibility iceberg.
AB  - Apolipoprotein E (APOE) is a true susceptibility polymorphism of the common form
      of Alzheimer's disease (AD). There are three APOE alleles (epsilon 2, epsilon 3,
      epsilon 4) that are universally distributed in the population with some variation
      in allele frequency due to racial and ethnic differences, and are associated with
      different risks and age of onset distributions. In multiple studies, the positive
      predictive value for symptomatic possible or probable AD patients who carry at
      least one epsilon 4 allele was consistently > 95%. Thus, early in the clinical
      course of dementia, when diagnoses are only 60-70% accurate, the presence of an
      epsilon 4 allele raises the diagnostic accuracy of AD to 95%. With the
      anticipation of a second major late-onset AD susceptibility locus on chromosome
      12, a matrix of relative susceptibility risks in the population raises many
      ethical and social questions associated with preclinical prediction. The
      metabolism of apoE (protein) in the brain is a new and exciting area of
      neurobiology research made relevant by the association with AD. We have
      constructed transgenic animals using large human genomic fragments containing
      human APOE on an APOE-deficit mouse background as well as homologous
      recombination experiments replacing mouse APOE with human APOE promoter elements.
      The APOE tissue elements, NOT the human APOE gene coding sequence, is associated
      with the human pattern of intraneuronal apoE immunoreactivity.

PMID- 9929680
TI  - Apolipoprotein E status is associated with odor identification deficits in
      nondemented older persons.
AB  - Alzheimer's disease (AD) patients with moderate dementia show losses in olfactory
      threshold, odor identification and odor memory. Sensitivity and specificity of
      olfactory testing is significant, with the greatest power of accurate diagnosis
      in the more cognitively loaded olfactory tasks. In patients with very mild AD or
      in patients at risk for the disease because of their mild cognitive impairment,
      losses are apparent for odor identification, odor recognition memory and odor
      threshold, with the best sensitivity in the identification task. Persons who are
      either heterozygous or homozygous for the epsilon 4 allele of apolipoprotein E
      (ApoE) have an increased risk of Alzheimer's disease, although they show no
      dementia in the preclinical period. Evidence of olfactory dysfunction in this
      population might be reflective of an incipient dementing process. We have
      recently examined olfactory function in a group of normal elderly persons who
      have undergone genetic testing for the Apoe4 allele. These individuals consisted
      of all normal control subjects at the University of California, San Diego (UCSD)
      Alzheimer's Disease Research Center (ADRC) who had undergone both the genetic
      testing and testing for olfactory function. All had been diagnosed as normal
      control participants by two different neurologists who applied the National
      Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and
      Related Disorders Association (NINDS-ADRDA) criteria for dementia. Persons with a
      history of alcoholism, drug abuse, learning disability or neurologic or
      psychiatric illness (including depression) were excluded. In this population,
      persons with the Apoe4 allele showed significantly poorer odor identification
      than those without an epsilon 4 allele. Early appearance of olfactory deficits in
      the progression to AD in persons with the epsilon 4 allele suggests diagnostic
      utility in olfactory testing.

PMID- 9929681
TI  - Viral replication in olfactory receptor neurons and entry into the olfactory bulb
      and brain.
AB  - This communication describes our ongoing studies of the interaction of the mouse
      host and vesicular stomatitis virus (VSV). When VSV is applied to the nasal
      neuroepithelium, it initially replicates in olfactory receptor neurons, and is
      transmitted along the olfactory nerve to the central nervous system (CNS) within
      12 hours. In the olfactory bulb, the virus replicates invasively through the
      layers of the olfactory bulb, reaching the olfactory ventricle by day 4-5 post
      infection, and the hindbrain by day 8 post infection. In mice, infection may
      result in a 50% mortality rate. The crucial host innate and specific immune
      responses responsible for restricting viral propagation and caudal spread of the
      virus will be discussed. The efficacy of interleukin-12 (IL-12) treatment for
      enhanced viral clearance and promotion of host recovery are described along with
      the implications for treatment of human encephalitis. The hosts' response to
      infection is also regulated by the sex of the host, and the age at infection. The
      role of specific mucosal humoral immunity and systemic cellular immunity in
      prevention of infection are described.

PMID- 9929682
TI  - Cellular and molecular neuropathology of the olfactory epithelium and central
      olfactory pathways in Alzheimer's disease and schizophrenia.
AB  - Specific deficits in odor detection threshold, identification, and memory have
      been recognized in a variety of disorders including the neurodegenerative
      disorder, Alzheimer's disease (AD), and the psychiatric illness, schizophrenia,
      which is likely due to abnormalities in neurodevelopment. Neuropathological
      abnormalities in peripheral and central olfactory systems have been described in
      both disorder. In the olfactory, epithelium, dystrophic neurites that are
      immunoreactive for tau, neurofilaments and other polypeptides, as well as
      deposits of beta-amyloid have been observed, and these findings have been thought
      to contribute to the olfactory dysfunction of these disorders. However, similar
      findings also occur in the olfactory epithelium of many normal individuals and
      those with various other neurodegenerative diseases. In contrast,
      neuropathological studies have reported selective vulnerability of central
      olfactory pathways for the accumulation of neurofibrillary pathology in AD, and
      for cytoarchitectural, neuronal morphometric, and cytoskeletal protein
      abnormalities suggestive of abnormal neurodevelopment in schizophrenia. Thus, it
      is likely that the olfactory impairments associated with these diseases are due
      to damage within central olfactory pathways, and that they are further amplified
      by the less specific impairments associated with age-related sensory
      neuroepithelial abnormalities. Finally, both the olfactory epithelium and central
      olfactory pathways represent model systems in which to study the neurobiology of
      these disorders, which ultimately may yield clues with diagnostic and therapeutic
      utility.

PMID- 9929683
TI  - The effects of topical anesthesia on oral burning in burning mouth syndrome.
AB  - Burning mouth syndrome (BMS) is an oral pain disorder of uncertain origin.
      Central or peripheral pain mechanisms may play a role in the oral burning of BMS.
      We tested the effect of a topical anesthetic (dyclonine HCl) on patients'
      intensity ratings for oral burning, taste dysgeusia and the taste of two chemical
      stimuli (1.0 M NaCl and 1.0 M sucrose). A total of 33 patients (9 male and 24
      female, average age: 60 yr) are included in this analysis. The anesthetic reduced
      the perceptual intensity of both chemicals in these patients on four out of five
      postanesthesia trials (p < 0.01). The BMS cohort included 12 patients whose
      burning increased (p < 0.001), 14 patients whose burning did not change, and 7
      patients whose burning decreased (p < 0.001) after anesthesia. Baseline
      dysgeusias (n = 13) decreased in intensity (p < 0.001) after anesthesia,
      suggesting BMS dysgeusia is related to the activation of peripheral taste
      mechanisms. The results also suggest that BMS oral burning may be a disorder of
      peripheral pain pathways in some patients.

PMID- 9929684
TI  - Olfactory dysfunction in multiple sclerosis. Relation to plaque load in inferior
      frontal and temporal lobes.
AB  - The question of whether and to what degree multiple sclerosis (MS) influences the
      ability to smell is controversial. We administered the University of Pennsylvania
      Smell Identification Test (UPSIT) to 26 MS patients and concurrently employed
      high-resolution magnetic resonance imaging (MRI) to quantify the number of
      demyelinating plaques within central brain structures. 38.5% of the patients
      demonstrated olfactory loss, with 7.7% exhibiting severe microsmia, 19.2%
      moderate microsmia, and 11.5% mild microsmia. None was anosmic, and no consistent
      left:right asymmetry in olfactory function or in hemispheric plaque numbers was
      observed. A strong negative correlation was found (Spearman r = -0.94) between
      UPSIT scores and the number of plaques within the inferior frontal and temporal
      lobes, but not within the rest of the brain. This study unequivocally
      demonstrates that a sizable proportion of MS patients suffer from olfactory loss
      commensurate with plaque activity within olfactory-related central brain regions,
      and is the first to explicate a physical basis for the olfactory dysfunction of
      any common neurologic disease.

PMID- 9929685
TI  - Rapid clinical evaluation of anosmia in children: the Alcohol Sniff Test.
AB  - Smell impairment affects 1-2% of Americans and leads to frequent physician
      visits. Olfactory functional testing is available in chemosensory centers, but is
      frequently omitted in routine cranial nerve examinations. A new smell test, using
      the standard 70% isopropyl alcohol pad, was developed at the UCSD Nasal
      Dysfunction Clinic: The Alcohol Sniff Test (AST). The current study examined the
      reliability of the AST in children, using test-retest measures. A standard 70%
      isopropyl alcohol pad was moved upward 1 cm per exhalation until the participant
      reported detection. Test-retest reliability of the AST in children was
      significant, r = 0.80. The AST predictably classified children as anosmic,
      hyposmic or normosmic, p < 0.0001. The AST requires only 5 minutes to administer
      with materials readily available in any physician's office or hospital. The AST
      is an effective screening tool, even in children, for the average physician who
      can then refer patients who show less than normal function for further
      comprehensive testing.

PMID- 9929686
TI  - PROP (6-n-propylthiouracil) supertasters and the saltiness of NaCl.
AB  - Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6-n
      propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that
      those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In
      recent years, we have classified tasters into two groups: medium (PROP is
      moderately bitter) and supertasters (PROP is intensely bitter). With our
      classification, approximately 25% of Americans are nontasters, 50%, medium
      tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive
      group. Anatomical studies showed that supertasters have the most fungiform
      papillae. Psychophysical studies showed that supertasters perceive the most
      intense bitterness and sweetness from a variety of compounds, the most intense
      burn from oral irritants, and the most intense tactile sensations from viscous
      solutions. Oral burn and touch are presumably perceived to be the most intense to
      supertasters because taste buds in fungiform papillae are innervated by the
      trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste). The
      psychophysical scaling method used was magnitude matching with NaCl as the
      control modality. With this method, subjects rated the intensities of a series of
      NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with
      PROP status allowed comparisons of the bitterness of PROP across subjects. Early
      magnitude matching studies, using sound as the control, had suggested that this
      assumption was reasonable. However, recent studies challenged that conclusion.
      Larger samples with more diverse populations, using sound as the control, showed
      that the taste of NaCl varied with PROP bitterness; supertasters perceived the
      strongest taste and nontasters, the weakest. Thus our earlier conclusions were
      conservative because differences between nontasters, medium tasters, and
      supertasters were concealed by using NaCl as a standard. Using magnitude matching
      with sound as the standard, or using the Green scale, which employs intensity
      labels, we found that the differences between PROP groups are larger. Note that
      the association between PROP status and salt taste is interesting in itself,
      since variability in salt taste may have important nutritional consequences.

PMID- 9929687
TI  - Sensory responses to 6-n-propylthiouracil (PROP) or sucrose solutions and food
      preferences in young women.
AB  - Genetic sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) has been
      linked with a greater number of food aversions and reported rejection of some
      bitter foods. Healthy young women (n = 121) were divided into nontasters, tasters
      and supertasters of PROP according to their PROP detection thresholds and the
      ratio of intensity ratings of PROP versus NaCl solutions. Hedonic response
      profiles to sucrose solutions distinguished between likers and dislikers of
      sweet. All subjects completed a 171-item food preference checklist. Food
      preference data were reduced by factor analyses, subscales of which were tested
      for reliability using Cronbach's alpha. Greater PROP sensitivity was associated
      with lower acceptance of coffee, cruciferous vegetables, tart citrus fruit, dark
      breads, and selected fats. In contrast, liking for sucrose solutions was linked
      to liking for sugar in tea and coffee, but not to any special pattern of food
      acceptance. Strategies aimed at increasing the consumption of grains, vegetables,
      and fruit should consider the role of inherited taste makers and their potential
      impact on dietary habits.

PMID- 9929688
TI  - PROP taster status is related to fat perception and preference.
AB  - Individuals who are sensitive to the bitter compound 6-n-propylthiouracil (PROP)
      are also more sensitive to selected bitter and sweet substances, to sharp foods
      and to the trigeminal irritant capsaicin. PROP tasters have a greater density of
      fungiform papillae, and it is speculated that they also have more trigeminal
      innervation. Since oral texture perception is also mediated, in part, by
      trigeminal fibers, it has been proposed that individual differences in fat
      perception might also be linked to PROP taster status and taste bud density. This
      work tests the hypothesis that individuals who are PROP tasters: (i) have a
      higher density of fungiform papillae; (ii) are more sensitive to capsaicin; and
      (iii) have increased ability to discriminate differences in fat content in salad
      dressing. Hedonic ratings for the salad dressing were also collected and related
      to the perceptual judgments. Individual subjects were classified as PROP
      nontasters, medium tasters or supertasters (n = 25/group) by comparing their
      psychophysical function for PROP to that of NaCl. Papillae densities
      (papillae/cm2) were significantly different among the three taster groups (p <
      0.0001), and were highest among the supertasters. Both medium tasters and
      supertasters perceived more oral burn from capsaicin than did nontasters at
      concentrations of 50, 70 and 100 ppm (p < 0.0001). Medium tasters and
      supertasters could also discriminate differences in fat content between 40% fat
      and 10% fat salad dressings (p < 0.005), but the nontasters could not. Although
      medium and supertasters showed no preference for either dressing, the nontasters
      preferred the 40% fat sample. The reasons for these latter findings are unclear
      at present. These data support the hypothesis that fat perception and preference
      can be linked to genetic and anatomical differences between individuals.

PMID- 9929689
TI  - Taste changes across pregnancy.
AB  - We examined taste intensity and preference in 46 pregnant and 41 healthy female
      controls enrolled in the Yale Pregnancy Study (J. Rodin, PI). Pregnant females
      were tested non-pregnant (non-pg) and during the first, second and third
      trimesters; controls, at corresponding time intervals. Subjects rated intensity
      of and preference for a three-member concentration series of NaCl, sucrose,
      citric acid (CA), and quinine hydrochloride (QHCl) on a labeled line ('nothing'
      at the left, 'extremely' at 80%). Variance differences between groups were tested
      with the F distribution (p < 0.05). Controls had significantly greater variance
      among overall intensity ratings than pregnant females, most pronounced for QHCl.
      Controls did not have highest variance among overall hedonic ratings, but did
      have highest variance for sweet and QHCl ratings. Within pregnancy analyses were
      tested with the Friedman two-way ANOVA. Significant intensity changes occurred
      for moderate NaCl and QHCL concentrations (p < 0.005). For NaCl, intensity fell
      from non-pg and first trimester to second and third trimesters. For QHCl,
      intensity rose from non-pg to first trimester, and fell from first to second and
      third trimesters. In the hedonic ratings, significant changes occurred for top
      concentrations of NaCl (p < 0.05) and 0.001 M CA (p < 0.001), and moderate QHCl
      (p < 0.005). NaCl preference rose from non-pg to third trimester. Preference for
      CA fell from non-pg to first trimester and then rose from first to second and
      third trimesters. QHCl became less disliked from non-pg and first trimester to
      third trimester. SUMMARY: taste intensity and hedonic variance in controls may
      associate with menstrual hormone fluctuations. Pregnant women were aligned in
      pregnancy stage which may explain the lower variance. Taste intensity and hedonic
      changes across pregnancy could serve to support healthy pregnancy outcomes:
      increases in bitter intensity in first trimester to protect against ingesting
      poisons; changes in NaCl, sour and bitter preference later in pregnancy to
      support ingesting a varied diet.

PMID- 9929690
TI  - Threshold distributions of phenylthiocarbamide (PTC) in the Chinese population.
AB  - The ability to taste phenylthiocarbamide (PTC) is a well-documented Mendelian
      trait. Mapping and cloning the gene(s) responsible for the PTC tasting ability
      would help to delineate the molecular basis for the variations in PTC tasting
      ability in humans and to shed new light on taste chemosensory functions. In view
      of the spectacular successes in genome science, the positional cloning strategy
      seems to be a feasible approach to the isolation of the gene(s) underlying the
      PTC tasting ability. As a first step toward mapping the gene(s), we collected PTC
      taste threshold data on 106 individuals, most of them being university students,
      in Shanghai, China. Using various parametric and nonparametric statistical
      methods, we have found that the data set is best described by a bimodal
      distribution. The frequency of PTC nontasters is estimated to be 10%. This is
      consistent with the view that the PTC nontasting ability follows a recessive mode
      of inheritance. Several authors had previously reported PTC data on Chinese
      living outside China. Our data are, to our knowledge, the first ever collected
      from the Chinese population within China.

PMID- 9929691
TI  - The perceived bitterness of beer and 6-n-propylthiouracil (PROP) taste
      sensitivity.
AB  - Pelchat and Danowski found a significantly higher proportion of nontasters of 6-n
      propylthiouracil (PROP) among children of alcoholics than among children of
      nonalcohlics, suggesting a possible genetic association between alcoholism and
      PROP tasting ability. They suggested that nontasters may not find alcohol as
      bitter as tasters do and may be at greater risk for alcoholism because they like
      the taste of alcoholic beverages more. In the present study we tested this
      hypothesis by examining how nontasters, medium tasters, and supertasters of PROP
      judged the taste of two kinds of beer. Forty-seven males and 53 females between
      the ages of 21 and 49 rated the perceived bitterness of Budweiser and Pilsner
      Urquell on the oral Labeled Magnitude Scale (LMS). Subjects also rated their
      degree of liking or disliking for the two beers on a 9-point Likert scale. PROP
      papers and the LMS were used to classify subjects into tasting groups. The
      results lent some support to the hypothesis in that male nontasters liked the
      taste of Pilsner Urquell better than male supertasters, when they tasted Pilsner
      Urquell after Budweiser. (This finding was not replicated for females). Also, as
      subjects' ratings of bitterness for the two beers increased, their degree of
      liking for the taste decreased. Supertasters rated Pilsner Urquell significantly
      more bitter than medium tasters. Subjects were asked about their drinking habits,
      and supertasters reported consuming significantly less beer than nontasters when
      they first started drinking beer on a regular basis. There were no significant
      differences in current drinking behavior between tasting groups. These results
      suggest that supertasters are distinct from nontasters with regard to their taste
      for beer and may to some degree be protected against alcoholism by their dislike
      for bitter substances.

PMID- 9929692
TI  - Psychophysical measurement of 6-n-propylthiouracil (PROP) taste perception.
AB  - The ability to taste 6-n-propylthiouracil (PROP) is genetically determined. PROP
      tastes moderately bitter to 'medium tasters' (MT), intensely bitter to
      'supertasters' (ST), and tasteless to 'nontasters' (NT). The psychophysical
      method used to characterize PROP status should capture the entire range of
      perception, while minimizing context, ceiling and other effects. Magnitude
      estimation successfully captures the variability in PROP perception, but requires
      normalization and may be difficult to conduct in industrial settings. Two labeled
      scales were tested as part of three separate studies (S1, S2 and S3) to measure
      perceived intensity of PROP and sweeteners. All studies included reportedly
      healthy volunteers aged 21-62 years recruited at Cultor Food Science in Groton,
      CT. In S1 [n = 163 (55 males, 108 females)], subjects rated perceived intensity
      of PROP-saturated paper and sucrose (1.0 M) on the Labeled Magnitude (Green)
      Scale (LMS) [labeled line with descriptors (no taste--strongest imaginable)]. In
      S2 [n = 152 (49 males, 103 females)], subjects rated perceived intensity of
      sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on the LMS. In S3 [n = 136
      (48 males, 88 females)], subjects rated perceived intensity of sucrose (1.0 M)
      and PROP solutions (0.001 M, 0.0032 M) on a 9-point category scale (1 = not at
      all; 9 = extremely). In all experiments, water rinses were included between each
      tastant and PROP was the final stimulus. Statistical analyses included
      descriptive statistics, regression analysis, and ANOVA. In S1 and S2, those with
      higher PROP perception perceived sucrose more intensely [(S1: r = 0.32; p <
      0.001); (S2: r = 0.25; p < 0.01)]. A higher frequency of females were ST than
      males. Also, the PROP effect on sweet perception was most evident in female ST.
      This apparent sex difference may be the result of hormonal variation associated
      with menstruation. As well, in S1 and S2 subjects aged 20-40 years, females had
      significantly greater variance among sucrose intensity ratings than males (F =
      3.66; p < 0.01), which may be due to hormonal changes with menses. The S3 results
      failed to show either the positive correlation between PROP and sucrose
      perception or the sex difference. Thus of the two labeled scales, the LMS appears
      to be better for assessing PROP perception, as it is continuous and also
      minimizes ceiling effects. Future research will extend these studies by including
      sucrose and high intensity sweetener concentration series.

PMID- 9929693
TI  - Comparison of the Green scale versus magnitude estimation for taste perception.
AB  - The Green scale is a new psychophysical method that is simple for subjects to
      use, but its relation with magnitude estimation has yet to be fully
      characterized. In comparing the consistency between the Green scale and magnitude
      estimation, we found that the former seems to provide a psychological oral
      sensation measurement that is different from the latter method. A simple
      correction formula can be derived.

PMID- 9929694
TI  - Effect of gelatin (a model for salivary PRP) on the sensory astringency of 5-O
      caffeoylquinic acid and tannic acid.
AB  - The present work investigates differences (triangular tests) between the
      astringency of 5-O-caffeoylquinic acid (5-CQA) and that of 5-CQA + gelatin. As an
      overall reference similar tests are reported using tannic acid (which has been
      shown to elicit a strong response). Finally, a time-intensity study on aqueous
      solutions of tannic acid (TA), TA + gelatin and gelatin, reveals relevant
      temporal factors. Although, under the experimental conditions, the majority of
      comparisons revealed statistically significant differences, in the time-intensity
      study no significant differences were found between TA + gelatin and gelatin,
      either for the intensity or the total duration of the response. Moreover, for the
      fading of the response there was no difference between TA + gelatin and TA. The
      main temporal contribution to the difference is in the onset of the response and
      can be related to the spectral differences observed in the earlier studies. It
      will be argued that these results may represent an important step in our
      understanding of the mechanisms of astringency.

PMID- 9929695
TI  - Oral irritant effects of nicotine. Psychophysical evidence for decreased
      sensation following repeated application of and lack of cross-desensitization to
      capsaicin.
AB  - When delivered to the oral mucosa, a variety of naturally occurring chemicals
      such as capsaicin from red chili peppers, piperine from black pepper, and
      nicotine from tobacco, cause a diffuse burning sensation often referred to as
      irritation. The burning sensation evoked by capsaicin increases when delivered
      repeatedly at 1 min intervals (sensitization), but then decreases markedly
      following a 10 min rest period (self-desensitization). It is also interesting
      that following desensitization by capsaicin, irritant sensations evoked by other
      chemicals are also reduced (cross-desensitization), suggesting that oral
      irritation from some agents may be mediated by a population of capsaicin
      sensitive trigeminal polymodal nociceptors. Although nicotine is a major
      component in tobacco smoke, little is known about its sensory properties.
      Accordingly, a study of the oral irritant effects of nicotine as compared with
      capsaicin was initiated. Whereas capsaicin (0.5 or 3 ppm; repeated at 1 min
      intervals over 10 min) evoked significantly stronger sensations (sensitization),
      there was a significant decrement in sensations to repeated application of
      nicotine (0.1%). After the subjects had received either repeated capsaicin or
      nicotine on one side of the tongue, a rest period ensued followed by a bilateral
      application of either capsaicin or nicotine. Subjects were, then, asked to choose
      which side yielded a stronger sensation (two-alternative forced choice).
      Following capsaicin pretreatment, all subjects reported that capsaicin evoked a
      stronger sensation on the previously untreated side (capsaicin self
      desensitization). Similar self-desensitization was observed with nicotine.
      Furthermore, nicotine was reported to evoke a significantly weaker sensation on
      the side of the tongue pretreated with capsaicin (cross-desensitization). In
      contrast, equal numbers of subjects reported capsaicin to evoke a stronger
      sensation on either the nicotine-pretreated side or the untreated side,
      indicating an absence of cross-desensitization. These results are discussed in
      terms of physiological mechanisms that might underlie the contrasting sensory
      effects of nicotine versus capsaicin.

PMID- 9929696
TI  - Detection of very complex taste mixtures.
AB  - Mixtures can often be tasted when all components are too weak to be tasted
      separately. Such mixtures are said to be integrative. Integration was
      demonstrated by mixing compounds in concentrations proportional to their separate
      detection thresholds and then measuring the detection threshold of the mixture as
      a whole by forced choice with plain water. Mixtures of 3, 6, 12 and 24 compounds
      were thus evaluated. With earlier data on 2-, 3- and 4-component mixtures, the
      results show that the concentration of any constituent compound goes down in
      approximate proportion to the number of compounds with which it is in mixture.
      This nearly complete integration describes mixtures of like-quality compounds, of
      unlike-quality compounds, and of both like- and unlike-quality compounds
      together. Integrative mixtures provide a model for the detection of the
      ultracomplex stimuli of everyday life, such as foods and drinking waters.
      Although the degree of integration may trail off slightly with mixtures of high
      complexity, the results proffer no limit on the number of compounds that can be
      at least partially integrated. In principle, integration permits detection of
      natural substances whose myriad components could all be far below threshold. The
      mechanism of taste integration is speculative, but the facts are congenial to the
      hypothesis of multiple parallel channels for the processing of intensity and
      quality.

PMID- 9929697
TI  - Temporal processing of odor mixtures reveals that identification of components
      takes precedence over temporal information in olfactory memory.
AB  - Temporal processing of binary mixtures results in odorants being perceived in
      series separated by many hundreds of milliseconds. Since the odorant perceived
      first is the main suppressor, knowledge of the order of perception of two
      odorants can allow prediction of interactions in mixtures. The present study
      investigated the temporal coding of ternary mixtures composed of carvone,
      coniferan and triethylamine, and citralva, lillial and triethylamine using a
      specially constructed air-dilution olfactometer. The results indicated that even
      though each of the components could be readily identified in ternary mixtures, it
      was very difficult to indicate which odor was perceived first, with chance scores
      being recorded. The same outcome occurred even when the 'slowest' odorant was
      delivered 600 ms after the 'fastest' to the nose. It is proposed that olfactory
      memory gives precedence to identification of the components of mixtures rather
      than to their order of perception when more than two odorants are in a mixture.

PMID- 9929698
TI  - An integrated model of intensity and quality of odor mixtures.
AB  - Several models of how odors mix to form new percepts have been presented during
      the last decades. Almost all these models have concerned the perceived intensity
      of mixtures rather than the perceived quality of mixtures. In 1994 Olsson
      suggested an integrated model for how perceived intensity and quality of the
      mixture can be predicted from the perceived intensities of the single substances.
      A generalized version of this model is proposed here. The model can be viewed as
      an extension of vector summation. The current study reviews support for this
      model. In doing that, assumptions of the model are defined and tested against
      data. It is shown how odor interaction, when the process is seen from the view of
      the observer, reduces to a set of simple rules that are consistent across levels
      of intensity and combinations of odorants.

PMID- 9929699
TI  - The design principles of axilla deodorant fragrances.
AB  - There are a number of ways that deodorant products control malodor: a) by
      suppressing sweat, b) by inhibiting bacterial activity, and c) by covering
      malodor. The paper focuses on the Givaudan Roure methodology used to develop
      fragrances that effectively cover malodor. Several steps are involved in the
      development of a successful deodorant fragrance. First, we test for substantivity
      of the deodorant fragrance material in the axilla, using odor value technology.
      Second, using an in vitro test with reconstituted axilla odor, we determine the
      effectiveness of the substantive fragrance material with carefully screened
      panelists. Third, using a multichannel olfactive blender, the perfumer creates a
      fragrance heart with effective deodorant fragrance materials that cover malodor
      in the vapor phase. Finally, the hedonically pleasing heart is used to create the
      final fragrance, which is then optimized using our in vitro test method.

PMID- 9929700
TI  - Factors affecting the perception of naturalness and flavor strength in citrus
      drinks.
AB  - In two profiling experiments and one grouping experiment, panelists evaluated
      orange drinks in order to measure the effects of design variables, especially
      color, on basic tastes as well as on more consumer-like attributes such as flavor
      strength and naturalness. Naturalness was increased in one experiment by lowering
      degrees Brix or increasing quinine HCl. Low sweet-sour ratios were generally
      perceived as more natural. Pectin had no effect on naturalness. Flavor strength
      was increased consistently by augmenting levels of quinine HCl, sucrose, citric
      acid or degrees Brix. Addition of Cochineal Red increased sweetness and flavor
      strength but decreased the perception of naturalness for the aromas studied.

PMID- 9929701
TI  - Using sensory and instrumental data to interpret the effect of storage at
      elevated temperatures on aroma of Chardonnay wines.
AB  - The effect of elevated temperatures during storage on the aroma of commercial
      Chardonnay wines was monitored by sensory and instrumental methods. Aromas of
      wines stored at 40 degrees C for 0, 15, 30 and 45 days were profiled by
      descriptive analysis by a trained panel. Heated storage decreased intensity of
      fruity and floral notes, while increasing attributes such as honey,
      butter/vanilla, oak, and rubber. Volatiles recovered by solvent extraction from
      the same wines were separated by gas chromatography (GC) and identified by GC
      mass spectrometry (MS). Principal component analysis of instrumental variables
      (PCAIV) was used to reduce the initial set of 67 quantified GC peaks. Six
      compounds, selected by PCAIV to yield the configuration closest to that of the
      principal component analysis of the sensory data, provided a highly significant
      fit with the sensory configuration, as shown by a permutation test. This solution
      was the statistically optimal one, but was not unique, as demonstrated by
      significant fits between the sensory and instrumental spaces upon use of other GC
      peaks, which were highly correlated with the original six variables.

PMID- 9929702
TI  - Role of the taste system in ingestive behavior. Studies in NaCl and fatty acid
      transduction.
AB  - The transduction of tastants involves a variety of mechanisms both within and
      across stimulus classes. Taste stimuli have been shown to permeate and block ion
      channels, activate both ionotropic and metabotropic receptors and directly
      permeate the membrane of taste receptor cells. Though significant progress has
      been made in recent years in elucidating the mechanisms of taste transduction,
      there has been comparatively little emphasis placed upon investigating how the
      transduction process in taste receptor cells is modulated. Moreover, because of
      the general opinion that the sense of taste has little or no direct role in the
      regulation of ingestive behavior, there have been few studies aimed at directly
      assessing the link between the performance of the peripheral gustatory system and
      underlying nutritional preferences. Recent work in our laboratory in NaCl and
      fatty acid transduction supports the idea that the transduction of taste stimuli
      is a very dynamic process that both contributes to the control of ingestive
      behavior and is reflective of underlying nutrient preferences.

PMID- 9929703
TI  - Advances in the diagnosis and management of impotence.

PMID- 9929704
TI  - Urinary incontinence update: old traditions and new concepts.

PMID- 9929705
TI  - Advances in the etiology and treatment of venous thromboembolism.

PMID- 9929706
TI  - New knowledge of genetic pathogenesis of hemochromatosis and Wilson's disease.
AB  - Discovery of the gene for WD has greatly enhanced our understanding of this
      disorder at the cellular level and has set the stage for future testing of new
      modes of therapy. Improvements in analytic methods for detecting mutations in
      genomic DNA will someday enable a rapid and cost-effective method of screening
      for this disorder. Until then, the time-tested clinical and biochemical
      evaluation, including measurement of ceruloplasmin oxidase activity, slit-lamp
      examination for Kayser-Fleischer rings, and measurement of hepatic copper
      content, will continue to remain the standard for establishing the diagnosis of
      WD.

PMID- 9929707
TI  - Diagnosis and treatment of prolactinomas.

PMID- 9929708
TI  - Congenital adrenal hyperplasia in the adult patient.

PMID- 9929709
TI  - Management of osteoporosis.

PMID- 9929710
TI  - Newer therapeutic agents for asthma.
AB  - The past decade has seen significant advances in the available treatments for
      asthma. These include longer-acting bronchodilating agents, high topical potency
      inhaled corticosteroids, and agents that interfere with leukotriene production or
      action. Table 3 summarizes the clinical effects of the newer therapeutic agents
      reviewed. Experimental therapies for the steroid-dependent patient have also been
      discussed. Although clinical trials to date have established many of these as
      effective in asthma, the results of ongoing, large, multicenter studies
      investigating the relative merits of these therapies, alone and in combination,
      will further clarify how to maximize the utility of these agents in the treatment
      of asthma.

PMID- 9929711
TI  - Atrial fibrillation and anticoagulation.

PMID- 9929712
TI  - Diseases of the aorta.

PMID- 9929713
TI  - Myocarditis.

PMID- 9929714
TI  - Thrombolytic therapy.

PMID- 9929715
TI  - Adult immunization: principles and practice.

PMID- 9929716
TI  - Cytokines are critical in linking the innate and adaptive immune responses to
      bacterial, fungal, and parasitic infection.

PMID- 9929717
TI  - Ethics and genetic testing.
AB  - The tremendous growth in knowledge about genes and genetic technologies will
      eventually enable us to know individual genotypes and susceptibilities to
      disease, perhaps even before birth. Each new genetic test developed raises
      serious issues for individuals and society on the circumstances under which
      genetic information should be sought and the uses that should be made of such
      information. Ethical reflection and analysis will help us to prepare for the
      responsible use of information about genotypes so that individuals, both now and
      in the future, are benefited and not harmed, so that justice is served, and so
      that confidentiality and privacy, and respect for the autonomy, dignity, and
      differences of each individual, are preserved.

PMID- 9929718
TI  - [Current status of the treatment of idiopathic pulmonary fibrosis].

PMID- 9929719
TI  - [Assessment of lung function using forced impulse oscillometry in cystic fibrosis
      patients].
AB  - The aim of this study was to evaluate the usefulness of forced impulse
      oscillometry to measure airway resistance in patients with cystic fibrosis.
      Thirty-four patients (20 men) with a mean age of 15 +/- 4 years were studied. All
      patients underwent forced impulse oscillometry, forced spirometry and body
      plethysmography. Correlations among spirometric, plethysmographic and
      oscillometric variables were analyzed. We found a statistically significant
      relation between both forced expiratory volume in one second (FEV1) and total
      airway resistance (Raw) and the following oscillometric variables: impedance
      (Zrs), resonance frequency (Fres), resistance to 5 hertz (Rrs5) and reactance to
      5 hertz (Xrs5). The measurements that correlated most highly with classical
      pulmonary function tests were Zrs and Xrs5. Both resistance (Rrs) and reactance
      (Xrs) of the respiratory system were dependent on frequency. Their correlation
      with FEV1 and Raw were therefore lower when frequencies above 5 hertz were used.
      We conclude that airway resistances of cystic fibrosis patients can be adequately
      estimated by forced impulse oscillometry. This technique is a promising test of
      pulmonary function in such patients.

PMID- 9929720
TI  - [Smoking in young military men: attitudes and characteristics].
AB  - This study aimed to determine the attitudes toward smoking and the
      characteristics of smoking patterns in young men of military age. Individuals
      performing their military service were surveyed using a self-administered,
      anonymous, personal and voluntary questionnaire. Questions were included on
      smoking habits, social context, and desire to quit. Responses were received from
      386 (93.46%) subjects, all male, whose mean age was 20.52 +/- 2.3 years. The
      sample included 207 smokers (53.62%), 173 non smokers (44.81%) and 6 ex-smokers
      (1.55%). Mean age of initiation was 15.07 +/- 2.4 years and mean age of start of
      habitual smoking was 16.46 +/- 2.2 years. The main reasons for starting to smoke
      were curiosity (39.73%) and peer pressure (29.45%). Between 11 and 20
      cigarettes/day were smoked by 53.74%. Those who began before 18 years of age
      smoked more than those who began after age 19. Light tobacco was smoked by
      90.87%. Non smokers had fewer friends and family members who smoked than did
      smokers (p < 0.05). The proportion of moderate smokers was 78.85%. Forty-three
      percent were found to be in a phase of thinking about quitting, and 48.19% had
      previously tried to quit. Anxiety is the most common cause of re-commencement.
      Stress was cited most often as the reason for increased smoking. We conclude that
      the prevalence of daily smoking is high among young men, who begin smoking
      regularly at 16 years of age. Those who begin later smoke less. The influence of
      friends and family members on initiation and maintenance of smoking is great.
      Half the smokers contemplated quitting and reported a high number of earlier
      attempts to stop. We believe that military quarters are an ideal place for health
      education and promotion, offering the possibility of designing special programs
      for decreasing the prevalence of smoking among adults.

PMID- 9929721
TI  - [Estimate of bibliometric indicators of the impact of +Archivos de
      Bronconeumologia].
AB  - The main bibliographic impact factors of ARCHIVOS DE BRONCONEUMOLOGIA for the
      past two years are estimated. Citations of ARCHIVOS DE BRONCONEUMOLOGIA in 1996
      and 1997 by Medicina Clinica and all citing journals grouped under the heading
      "Respiratory System" in the Science Citation Index were counted. The year the
      citation appeared and the year of publication of the article in ARCHIVOS DE
      BRONCONEUMOLOGIA were recorded. The total number of articles published by
      ARCHIVOS DE BRONCONEUMOLOGIA between 1994 and 1996 were also counted. Based on
      these data we calculated our journal's impact factor for each year studied.
      Relative impact factor was also figured. In 1996 the exposure factor achieved was
      1.602, the half-life of articles was 2.00 years, the impact factor was 0.069 and
      the relative impact factor was 1.371. In 1997 the exposure index was 1.477, the
      citation half-life was 3.00 years and the impact factor was 0.030. In conclusion,
      the international impact of ARCHIVOS DE BRONCONEUMOLOGIA is modest, although our
      relative impact factor is greater than that of some other internal medicine
      publications or specialized journals listed in Journal Citation Reports.

PMID- 9929722
TI  - [Usefulness of the quantification of the alpha-1 serous protein band in the
      screening of alpha-1-antitrypsin deficiency].
AB  - BACKGROUND: Population studies indicate that alpha-1-antitrypsin (AAT) deficiency
      is an under diagnosed disease. Although alpha-1 serum protein is widely known to
      accompany AAT deficiency, the diagnostic utility of measuring the alpha-1 band to
      screen for this condition has not been assessed in the literature. SUBJECTS AND
      METHOD: Electropherograms with alpha-1 band widths under the reference values
      were collected over a period of 3 months. The Pi phenotype of AAT was identified
      for these sera by isoelectric point determination. The phenotypes were compared
      to those obtained for the population of the same geographic area (n = 440). The
      alpha-1 band reference values were obtained from 73 healthy individuals with no
      Pi phenotype deficiency. Moreover, the alpha-1 band was also measured for a group
      of 17 PiZZ deficient patients. RESULTS: We analyzed 7,305 electropherograms. One
      hundred four individuals (1.4%) without hypoproteinemia had alpha-1 readings
      below reference (set at 2.3%). The phenotypes in this group were 25 PiMM (24%),
      52 PiMS (54%), 13 PiMZ (12.5%) and 5 PiSS 5 (5%). The odds ratios (CI 95%) in
      comparison with the normal population were, respectively, 0.10 (0.16-0.06); 4.58
      (2.97-7.04); 4.35 (2.09-9.04) and 5.51 (1.66-18.16) (p < 10-5 in all cases except
      PiSS, which was p < 0.05). The levels for PiZZ patients were 1.4% +/- 0.3% (range
      1.0%-2.1%). CONCLUSIONS: Three times fewer subjects with a normal PiMM phenotypes
      are found among individuals with low alpha-1 band serum protein levels, and many
      more of such individuals are carriers of Z allele heterozygotes. Alpha-1 band
      readings in patients with AAT deficiency (PiZZ phenotype) have alpha-1 values
      below reference. Measuring alpha-1 protein is an easy technique, within the
      expertise of any laboratory, and may be very useful for screening for AAT
      deficiency in patients with chronic respiratory diseases.

PMID- 9929723
TI  - [Better at home: a continuous health care program for patients with advanced
      chronic respiratory disease].
AB  - The objective of this study was to analyze the effect of continuous health care
      on the frequency of readmissions of patients with advanced chronic respiratory
      disease. The study was prospective, enrolling 26 patients (16 with COPD, 7 with
      bronchiectasis and 3 with pachypleuritis) who had been admitted at least 3 times
      within the past year. The patients were assigned to 3 groups: group A was the
      ambulatory monitoring group, with 8 patients who were able to travel to the
      hospital for monthly outpatient checkups; group B was the ambulatory pulmonary
      rehabilitation group, with 10 patients who were able to travel to the hospital
      and who needed rebreathing training (one weekly group session); and group C was
      the home care group, with 8 patients who were unable to travel to the hospital
      and who received weekly or biweekly house calls. All patients had telephone
      contact with the program team. Mean lung function values for the whole population
      were FVC 40 (11)%, FEV1 23 (7)% of reference, PaO2 55 (7) and PaCO2 55 (10) mmHg.
      A significant decrease in number of admissions (79 versus 18, p < 0.0001) was
      observed in both the first and second halves of the year in all three treatment
      groups: A, 25 to 2; B, 28 to 8; and C, 26 to 8 (p < 0.001). The reduction in
      health care costs over the previous year's expenditure was calculated to be
      22,751,402 pesetas. We conclude that specialized health care that is continuous
      and personalized reduces the number of hospital readmissions of patients with
      advanced chronic respiratory disease. Moreover, the overall cost of care, without
      the need to make house calls to all patients.

PMID- 9929724
TI  - [Immune protection against Mycobacterium tuberculosis. Role of interferon-gamma
      and T gamma-delta lymphocytes].

PMID- 9929725
TI  - [Alcohol and the lungs].

PMID- 9929726
TI  - [Acute interstitial pneumonia (Hamman Rich syndrome)].
AB  - We report the case of a 65-year-old woman with no history of respiratory disease
      who suffered onset of dyspnea after an episode of pseudoinfluenza. Dyspnea
      progressed such that within 15 days it was triggered by minimal effort. The
      patient died 15 hours after admission to our hospital, with a clinical picture of
      adult respiratory distress. Autopsy allowed us to rule out several diseases and
      arrive at a diagnosis of acute interstitial pneumonia, consistent with clinical
      course, anatomical and pathological findings as described in the literature.

PMID- 9929727
TI  - [Tobacco control in children, adolescents and young people: knowledge, prevention
      and action].

PMID- 9929728
TI  - [Usefulness of endoscopic lung biopsy in the diagnosis of rheumatoid lung
      nodules].

PMID- 9929729
TI  - [Continuous oxygen therapy in interstitial lung diseases].

PMID- 9929730
TI  - [Metastatic pleural effusion secondary to papillary carcinoma of the thyroid].

PMID- 9929731
TI  - [Miliary tuberculosis caused by Mycobacterium africanum].

PMID- 9929732
TI  - [Sleep apnea-hypoapnea syndrome: treatment strategy with CPAP].

PMID- 9929734
TI  - [Synthesis of inositol-containing glycophospholipids].
AB  - The results and problems of synthetic studies of natural inositol containing
      glycophospholipids as well as their biologically active fragments and structural
      analogs are reviewed.

PMID- 9929733
TI  - [Sphingolipids and cancer].
AB  - The qualitative and quantitative changes in sphingolipids (ceramides,
      sphingomyelins, glycosphingolipids) occurring under tumor growth are considered.
      The influence of these changes on cell functions and immunity as well as the role
      of dietary sphingolipids in cancer and "sphingolipid" therapy of tumors are
      discussed.

PMID- 9929735
TI  - [Antigenic mapping of cytochrome P450 101 (P450cam)].
AB  - Eighteen linear antigenic sites were found in cytochrome P450 101 (P450cam) from
      Pseudomonas putida by the peptide scanning method. These sites accounted for
      about 30% of the protein sequence. We found no sequences that completely
      coincided with the antigenic sites of P450cam in cytochromes P450 from other
      sources. The linear B-epitopes of P540cam were mainly localized on the boundaries
      separating the elements of the secondary structure. Seventeen of eighteen
      antigenic sites were found to be on the protein surface and accessible to water
      molecules. Many functionally important sites or amino acid residues of the
      P450cam molecules coincided or were in close proximity to the linear B-epitopes
      found.

PMID- 9929736
TI  - [Expression of mutant horse cytochrome c genes in Escherichia coli].
AB  - Here we describe genetically engineered constructs for the expression in
      Escherichia coli of genes for horse cytochrome c mutants. These constructs allow
      the expression of the cytochrome c genes together with hemeligase, an enzyme
      which covalently links heme to cytochrome. Careful selection of producer strains
      and the adjustment of the conditions of expression provided for expression levels
      of 10-15 mg of protein per liter of culture. This is by an order of magnitude
      greater than the expression previously achieved in yeast. A series of horse
      cytochrome c mutants were obtained in this way.

PMID- 9929737
TI  - [Transportation of cytotoxic liposomes to malignant cells using a carbohydrate
      determinant].
AB  - A method of the synthesis of lipophilic glycoconjugates (vectors) on the basis of
      polyethyleneglycol-containing detergent was proposed. It has been shown by flow
      cytofluorometry that fluorescent labeled liposomes equipped with beta-galactosyl
      conjugate are bound human leukosis HL-60 cells more effectively than liposomes
      embedded with the beta-glucosyl conjugate or vector-free liposomes. A new lipid
      derivative of antitumor drug rubomycin (daunorubicin), N-(rac-1,2-dioleoylglycero
      3-oxalyl)rubomycin (RubDG) has been synthesized. Liposomes loaded with RubDG and
      equipped with galactosyl vector showed higher cytotoxic activity in vitro against
      HL-60 cells than analogous unvectored liposomes or liposomes bearing glucosyl
      conjugate.

PMID- 9929738
TI  - [Synthesis of betulinic acid from betulin and study of its solubilization
      usingliposomes].
AB  - A method for betulinic acid synthesis from betulin was developed. Betulin was
      oxidized with chromium oxide (VI) into betulonic acid, which was reduced with
      sodium borohydride to yield a mixture of 3-hydroxy epimers containing 85% of the
      natural beta-epimer. Studying changes in light scattering by dispersions of
      liposomes with different contents of betulinic acid revealed that up to 10 mol %
      of this compound may be entrapped in liposomes. The dependence of the efficiency
      of the betulinic acid entrapment on liposome composition was studied. The
      presence of polyvinylpyrrolidone or Proxanol increased the resistance of
      betulinic acid-containing liposomes to aggregation. These polymers solubilized
      betulinic acid with the same efficiency as liposomes.

PMID- 9929739
TI  - A series of function blocking antibodies against the alpha v beta 3 integrin bind
      allosteric to the ligand binding site and induce ligand dissociation.
AB  - The alpha v beta 3 integrin plays a critical role in bone resorption,
      angiogenesis, and tumor cell invasion. A blockade of this receptor has
      therapeutic potential in osteoporosis, vascular restenosis, and cancer. In this
      report, we characterize the mechanism by which six monoclonal antibodies inhibit
      the function of alpha v beta 3. All six antibodies interact with a common site
      that is partially comprised of residues 164-202 within the beta 3 subunit. This
      domain is physically separate from the RGD binding site, and appears to regulate
      ligand binding allosterically. Thus, the blocking antibodies function, in part,
      by inducing the dissociation of ligand from alpha v beta 3. Although this family
      of antibodies is able to virtually abolish alpha v beta 3-mediated cell adhesion,
      they only block about one-half of soluble ligand binding to the integrin. This
      observation is consistent with the idea that two functionally distinct
      populations of alpha v beta 3 are present on the cell surface. The unique
      mechanism of action of these antibodies provides new insight in the structure
      function relationships of alpha v beta 3, and also suggest that such antibodies
      are likely to behave differently than RGD mimetics if used as drugs.

PMID- 9929740
TI  - Stimulation through CD50 preferentially induces apoptosis of TCR1+ human
      peripheral blood lymphocytes.
AB  - Apoptosis has an important role in several key immunological phenomena such as
      regulation of the immune response, and deletion of auto-reactive cells. This
      phenomenon is induced following the interaction of several cell membrane
      receptors with their respective ligands or after cell activation. We have studied
      the possible effect of signaling through CD50/ICAM-3 and CD69/AIM on apoptosis of
      peripheral blood lymphocytes. Apoptosis was assessed by both flow cytometry
      analysis (content of cell DNA and binding to annexin V), and detection of DNA
      fragmentation by agarose gel electrophoresis. We found that a stimulatory anti
      CD50 mAb was able to induce a small but significant degree of apoptosis in
      resting peripheral blood mononuclear cells from most donors; this effect was dose
      dependent and was evident as early as at 12 h, with a maximal induction at 48 h.
      Studies with T and non-T cells showed that only the former cell population was
      sensitive to the induction of apoptosis through CD50. Further experiments
      revealed that the anti-ICAM-3 mAb preferentially induced apoptosis of TCR gamma
      delta-bearing cells. In addition, we found a significant increase in Cai2+ in
      PBMC stimulated with an anti-CD50 mAb, suggesting the involvement of this
      signaling pathway in the induction of apoptosis through this adhesion receptor.
      In contrast, under our experimental conditions, stimulation through CD69 did not
      have any effect on the induction of apoptosis on either cultured T lymphoblasts
      or PMA-stimulated PBMC. Our findings suggest that the interaction of CD50 with
      its natural ligand LFA-1 results in the induction of apoptosis in a significant
      fraction of resting PBMC. This phenomenon may be involved in immune regulation,
      lymphocyte turnover and peripheral deletion of auto-reactive cells.

PMID- 9929741
TI  - Secreted, glycosylated arginase from Xanthoria parietina thallus induces loss of
      cytoplasmic material from Xanthoria photobionts.
AB  - A secreted, glycosylated arginase (lectin) from Xanthoria parietina thallus binds
      to the cell wall of Xanthoria photobiont when cell wall urease has previously
      been induced. The uptake of this secreted arginase by the algal cell without cell
      wall ligand for the lectin increases the concentration of algal putrescine and it
      is followed by an apparent loss of chlorophyll. However, neither chlorophyllase
      activity has been detected nor chlorophyllide concentration increases after
      loading the cells with putrescine. The loss of chlorophyll can be explained by
      the loss of algal protoplast resulting from the action of a putrescine-activated
      glucanase and the split of their membrane in an hypoosmotic medium. The loss and
      split of protoplasts have been shown by light and transmission electron
      microscopy.

PMID- 9929742
TI  - Each step during transendothelial migration of flowing neutrophils is regulated
      by the stimulatory concentration of tumour necrosis factor-alpha.
AB  - Migration of circulating neutrophils occurs in several steps: capture and rolling
      adhesion are followed by activation of beta 2-integrins and immobilisation, and
      then neutrophils move over and through the endothelium. However, it is not clear
      how the underlying mechanisms and completion of each step depend on the
      concentration of stimulatory cytokines such as tumour necrosis factor-alpha
      (TNF). We therefore perfused neutrophils over human umbilical vein endothelial
      cells (HUVEC) which had been cultured with varying concentration of TNF (1-1000
      U/ml) for 4 h, and recorded adhesion and migration by videomicroscopy. The number
      of adherent neutrophils increased with increasing TNF up to 5 U/ml, but changed
      little at higher concentrations. Interestingly, rolling adhesion at first
      predominated, but an increasing proportion of adherent cells became immobilised
      and migrated through the HUVEC monolayer over the complete TNF range.
      Immobilisation was inhibited by treating neutrophils with antibody against CD18,
      so that the major change in adhesive behaviour at higher levels of TNF occurred
      because the surface of the HUVEC presented agent(s) able to activate neutrophil
      beta 2-integrins. It was also evident that the selectins initiating capture of
      flowing neutrophils varied with concentration of TNF. At 100 U/ml TNF, both E
      selectin and P-selectin supported capture and rolling adhesion, and antibody
      blockade of both receptors was required to inhibit adhesion. At lower dose (10
      U/ml TNF), stable adhesion was blocked by antibody against E-selectin, although
      short-lived attachments could still be seen which were inhibited by antibody
      against P-selectin. Expression of sclectins increased with increasing
      concentration of TNF, judging from surface ELISA and reduction in the velocity of
      rolling adherent cells. Thus the efficiency of capture, the selectins mediating
      capture and the proportion of captured cells immobilised and migrating all depend
      on the concentration of TNF to which endothelial cells are exposed. These results
      suggest a model in which highly localised and efficient migration of neutrophils
      is achieved if a concentration gradient of TNF exists around an inflammatory
      locus.

PMID- 9929743
TI  - Calcium- and calmodulin-dependent PMA-activation of the CD44 adhesion molecule.
AB  - The ability of the CD44 adhesion molecule to interact with its ligand hyaluronic
      acid (HA) is tightly regulated. CD44-positive mouse LB lymphoma cells are unable
      to bind HA unless activated by the tumor promoter phorbol 12-myristate 13-acetate
      (PMA). PMA causes a dose-dependent increase in both CD44 expression level and HA
      binding capacity, with the binding of HA observed only above a threshold amount
      of CD44 molecules. This induction of HA-binding as well as the increase in CD44
      expression are prevented by cycloheximide, suggesting a requirement for new
      additional CD44 molecules on the cell surface and/or cooperating proteins. In the
      present study, we have investigated which of the signal transduction pathways
      activated by PMA leads to the increased CD44 expression with subsequent
      acquisition of HA-binding capacity. By comparing the influence of each inhibitory
      agent on PMA-activated LB lymphoma cells versus that on a constitutive HA-binder
      cell line derived from LB cells (designated HA9 cells), we could distinguish
      between an effect on the PMA-activation phase and a one on the HA-binding phase.
      Our data show that the PMA-induced HA-binding could not be blocked by agents
      inhibiting protein kinase C (PKC) (staurosporine, sphingosine, polymyxin B,
      quercetin) or genestein, an inhibitor of tyrosine protein kinases. However, this
      PMA response was strongly inhibited by calmodulin antagonists (chlorpromazine,
      trifluoperazine, W-7) and the calcium blocker verapamil. The calmodulin
      antagonists inhibited the PMA-induced increase in CD44 expression on LB cells,
      but had no influence on the ability of the constitutive HA-binder HA9 cell line
      to interact with HA, indicating an effect on the PMA induction phase rather than
      on the binding itself. Verapamil also blocked the PMA-induced increase in CD44
      expression on LB cells, but in addition it slightly reduced the ability of the
      HA9 cells to bind HA without affecting their CD44 expression level. In
      conclusion, our data suggest that CD44 activation by PMA is calcium and
      calmodulin dependent, rather than mediated by protein kinase C.

PMID- 9929744
TI  - Viagra, the latest cardio-VASCULAR drug.

PMID- 9929745
TI  - Coronary bypass surgery after an acute myocardial infarction: will delaying
      surgery decrease cardiac events?

PMID- 9929746
TI  - Single-vessel disease: what is the evidence favoring medical versus
      interventional therapy?

PMID- 9929747
TI  - The importance of randomized clinical trials and evidence-based medicine: a
      clinician's perspective.
AB  - Clinical evaluation of therapies for patient care has evolved during the
      twentieth century from a variety of scientific methods. As a result of medical,
      political, and economic changes that occurred in the 1990s, randomized clinical
      trials and evidence-based methods are presently in the forefront of the
      physician's thinking in the decision-making process for therapeutic
      interventions. A new standard of patient care has emerged during this process.
      This report provides a clinician's viewpoint of the importance and interpretation
      of evidence-based methods and suggests a strategy when such evidence does not
      exist.

PMID- 9929748
TI  - The role of cardiac troponin-I (cTnI) in risk stratification of patients with
      unstable coronary artery disease.
AB  - In patients with chest pain at rest but no ST-segment elevation on the
      electrocardiogram, the diagnoses of unstable angina and non-Q-wave myocardial
      infarction (MI) are usually considered together because they cannot be
      differentiated clinically or angiographically. Since the extent of myocardial
      necrosis is an important determinant of the risk of death, it is important to
      identify serum markers with which to predict prognosis, in order to initiate
      appropriate medical treatment and/or invasive procedures in these patients.
      Cardiac troponin-I (cTnI), one of the subunits of the troponin regulatory
      complex, binds to actin and inhibits interactions between actin and myosin. The
      presence of elevated cTnI in serum is a significant prognostic indicator in
      patients with unstable angina and non-Q wave MI. Its independent prognostic
      potential persists even after adjustment for independent baseline variables known
      to be significantly associated with an increased risk of cardiac events. The use
      of cTnI in the triage of patients with unstable coronary disease may identify
      those at greater risk for adverse cardiac events.

PMID- 9929749
TI  - Emergency department thrombolysis critical pathway reduces door-to-drug times in
      acute myocardial infarction.
AB  - BACKGROUND: Rapid time to treatment with thrombolytic therapy is an important
      determinant of survival in acute myocardial infarction (AMI). HYPOTHESIS: We
      hypothesized that establishment of an AMI thrombolysis critical pathway in the
      Emergency Department could successfully reduce the "door-to-drug" time, the time
      between patient arrival and start of thrombolysis. METHODS AND RESULTS: Before
      establishment of the AMI critical pathway, median door-to-drug time was 73 min,
      which was reduced to 37 min after critical pathway implementation (p < 0.05). The
      percentage of patients treated within 30 min rose from 0% prior to establishment
      of the pathway to 43% (p = 0.03). Similarly, the percentage treated in within 45
      min rose from 0 to 67% (p = 0.0005). Door-to-drug times were longer for women
      than for men (median 105 min for women vs. 70 min for men before pathway
      implementation). The pathway reduced door-to-drug time for both genders, but the
      median door-to-drug times were higher for women than for men (Mann-Whitney p =
      0.013). The difference between men and women was 35 min before establishment of
      the pathway to 10 min by the end of the study period. CONCLUSIONS: Our critical
      pathway was successful in reducing door-to-drug times. We observed a "gender gap"
      in door-to-drug times, with longer mean times for women, which was reduced by the
      AMI critical pathway. Thus, our data provide support for the use of critical
      pathways to reduce door-to-drug times, as recommended by the National Heart
      Attack Alert Program.

PMID- 9929750
TI  - Effect of balloon inflation-induced acute ischemia on QT dispersion during
      percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: QT dispersion (QTd = QTmax-QTmin) measured as interlead variability
      of QT interval reflects the spatial inhomogeneity of ventricular repolarization
      times, and increased QTd may provide a substrate for malignant ventricular
      arrhythmias. Ischemia is associated with regional abnormalities of conduction and
      repolarization. HYPOTHESIS: This study aimed to investigate the effect of acute
      ischemia on QTd during successful percutaneous transluminal coronary angioplasty
      (PTCA). METHODS: Forty-three patients (10 women, 33 men, mean age 56 years) were
      enrolled in the study. Electrocardiogram (ECG) recordings were taken before PTCA
      and during balloon inflation period. QT maximum (QTmax), QT minimum (QTmin), and
      QTd (QTmax-QTmin) values were calculated from the surface ECG. RESULTS: There was
      no difference among QTmax values (p = 0.6). Mean QTmin during balloon inflation
      was lower than before PTCA (368 +/- 45 vs. 380 +/- 41 ms, p = 0.002). The
      difference between QTd values before and during balloon inflation was
      statistically important (65 +/- 9 vs. 76 +/- 10 ms, p = 0.001). This difference
      is caused by a decrease in QTmin during balloon inflation. CONCLUSION: Acute
      reversible myocardial ischemia induced by balloon inflation causes an increase in
      QTd value, and this increment is the result of a decrease in QTmin interval.
      Therefore, QTd may be a marker of reversible myocardial ischemia.

PMID- 9929751
TI  - Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia.
AB  - BACKGROUND: Combined HMG-CoA reductase inhibitor and fibric acid derivative
      therapy is often necessary for the effective reduction of concentrations of low
      density lipoprotein (LDL) cholesterol and triglycerides in patients with mixed
      hyperlipidemia; however, the potential risk of myopathy has limited the use of
      these agents. HYPOTHESIS: This study evaluated long-term safety and efficacy of
      combined pravastatin and gemfibrozil therapy. METHODS: Eighty-three patients with
      hyperlipidemia were treated with combined pravastatin and gemfibrozil therapy for
      a median of 44 months (range 9-78 months). Plasma lipids, serum liver function
      tests, creatinine, and creatinine kinase (CK) levels were measured every 3 to 4
      months. RESULTS: One patient developed myalgia with a normal CK level after 4
      months of combination therapy. Three patients had transient elevations in CK
      levels that ranged from 3 to 5 times the upper limits of "normal" and that
      returned to normal upon repeat testing. Liver function tests did not change
      significantly from baseline. In a subset of 26 previously untreated patients,
      combined pravastatin (mean daily dose 22 mg) and gemfibrozil (mean daily dose
      1,154 mg) therapy lowered total cholesterol by 25% (p < 0.001), triglycerides by
      53% (p = 0.0001), LDL cholesterol by 14% (p = 0.24), and increased high-density
      lipoprotein (HDL) cholesterol by 20% (p = 0.012). CONCLUSION: Pravastatin and
      gemfibrozil therapy is safe and efficacious in patients with mixed
      hyperlipidemia. The long-term safety results are consistent with other reports on
      follow-up of shorter duration.

PMID- 9929752
TI  - Randomized evaluation of four versus five French catheters for transfemoral
      coronary angiography.
AB  - BACKGROUND AND HYPOTHESIS: In coronary angiography there is a trend toward using
      smaller catheters to avoid puncture site complications. An increased utilization
      of outpatient facilities may result. This study was undertaken to determine
      whether using 4Fr diagnostic catheters in comparison with 5Fr catheters would
      reduce the vascular complication rate, after patient ambulation following 4 h
      bedrest, without altered technical performance and or procedural duration.
      METHODS: The study population comprised 100 consecutive, unselected patients, who
      were randomly assigned for transfemoral coronary angiography with 4 or 5Fr
      diagnostic catheters. Procedural characteristics, quality of angiogram, and
      clinical assessment of puncture site at 4, 12, and 24 h were analyzed. RESULTS:
      No significant difference was demonstrated concerning procedural characteristics,
      ventriculography, coronary contrast quality, or local vascular damage. However,
      two patients crossed over in the 4Fr group and one in the 5Fr group. CONCLUSION:
      As a consequence, the feasibility, reliability, and utility of catheter size on
      vascular complication rates must be considered to be similar with either 4Fr or
      5Fr diagnostic catheters.

PMID- 9929753
TI  - Cardiac and autonomic evaluation in a pediatric population with human
      immunodeficiency virus.
AB  - BACKGROUND: Cardiac involvement in children with human immunodeficiency virus
      (HIV) infection is a well-known entity and occurs clinically more often in
      patients with advanced acquired immunodeficiency syndrome (AIDS). Autonomic
      dysfunction is less known, especially in children. HYPOTHESIS: The aim of this
      study was to asses the prevalence of cardiovascular abnormalities in a pediatric
      population with HIV. We also aimed to evaluate whether autonomic involvement
      occurs in the same population and is dependent on echocardiographic
      abnormalities. METHODS: The occurrence of echocardiographic abnormalities was
      evaluated in 22 children with HIV infection, and five noninvasive tests were
      performed to evaluate the presence of autonomic dysfunction. RESULTS: We found
      cardiac lesions in four children (18%), consisting of pericardial effusion in
      three children, wall motion abnormalities in three children, and acute aortic
      endocarditis in one child. All cardiac abnormalities were found at Stage C by
      Center for Disease Control (CDC) revised classification. We also found left
      ventricular filling pattern abnormalities consisting of E-wave maximal velocity
      decrease and prolonged deceleration time compatible with diastolic dysfunction.
      One of the five autonomic tests (Valsalva maneuver) was significantly altered,
      even in patients without abnormal echocardiography, suggesting mild autonomic
      dysfunction. CONCLUSION: The study demonstrated a high prevalence of cardiac
      lesions in children with HIV infection and indicated the presence of autonomic
      dysfunction even when there are no echocardiographically detected abnormalities.

PMID- 9929754
TI  - Electrocardiographic patterns in acute inferior myocardial infarction with and
      without right ventricle involvement: classification, diagnostic and prognostic
      value, masking effect.
AB  - BACKGROUND: In acute inferior myocardial infarction (AIMI), the ST depression
      from V1 to V4 has been the subject of many papers, while the ST changes in other
      leads, their association, and the right ventricular (RV) involvement have been
      studied less. HYPOTHESIS: This study was performed to contribute to the meaning
      of the ST changes and RV involvement in AIMI. METHODS: Seventy-one patients,
      admitted within 6 h from symptom onset, all thrombolysed, were enrolled. We
      classified them according to ST patterns and RV involvement. We divided the right
      coronary artery into three segments, considering the origin of RV branch and the
      crux as dividing points. We established a coronary score attributing 2 points to
      each terminal branch. Comparisons were performed between the electrocardiographic
      (ECG) findings at onset, the creatine phosphokinase (CPK) peaks, the radionuclide
      ejection fractions, and the coronary angiographies. RESULTS: We found that the ST
      changes give indications regarding the site, extension, and extent of AIMI; RV
      involvement can mask posterior extension, points to the right coronary as the
      culprit vessel (100%), and, with high probability, indicates the proximal segment
      as the site of the lesion; the ECG signs of isolated AIMI indicate a peripheral
      obstruction; and a collateral circulation may appear relatively early.
      CONCLUSIONS: Our findings prove the diagnostic and prognostic value of the ST
      changes and RV involvement at the onset of AIMI and suggest that the higher in
      hospital mortality and complication rates found with RV involvement and reported
      in the literature are related more to posterior extension, masked by RV
      involvement than to this involvement per se. Furthermore, these findings prove
      the clinical value of our classification of the AIMIs and distinction in segments
      of the right coronary artery.

PMID- 9929755
TI  - Impending paradoxical embolism: a transesophageal echocardiographic image.

PMID- 9929756
TI  - Acute prosthetic mitral valve failure.

PMID- 9929758
TI  - Louis Gallavardin.

PMID- 9929757
TI  - Angiotensin-converting enzyme inhibitor-induced pancreatitis.
AB  - Approximately 2% of pancreatitis in adults is drug induced. Although some
      angiotensin-converting enzyme (ACE) inhibitors have been associated with
      pancreatitis, to the knowledge of the authors this is the first reported case
      involving benazepril. This case report presents laboratory- and image-proven
      pancreatitis in a noninsulin dependent 70-year-old man. The patient took
      benazepril at three different times and experienced the same epigastric symptoms
      30 min after each dose. Possible mechanisms are reviewed. Clinicians should
      strongly consider discontinuing ACE inhibitors, including benazepril, in patients
      with pancreatitis of no identifiable source.

PMID- 9929759
TI  - Microphysiology of the pericardium in relation to intrapericardial therapeutics
      and diagnostics.
AB  - Intrapericardial delivery of therapeutic agents for pericardial diseases has long
      been available in the presence of excess pericardial fluid. Most patients with
      myocardial and coronary disease have no such excess so that their direct
      treatment requires pericardial access, for which a new instrument has succeeded
      in animals with induced infarctions, coronary lesions and arrhythmias. Nitric
      oxide (NO) donors, calcium-avid drugs, antibodies, angiogenic agents
      (pharmacologic coronary bypass), and hypothermic solutions have been instilled
      intrapericardially, and even iontophoresis has been used; gene therapy is also
      promising. Intrinsic pericardiogenic substances may potentially be stimulated for
      comparable purposes.

PMID- 9929760
TI  - Function of the normal pericardium.
AB  - Until recently, instrumenting the pericardium was possible only when a
      pericardial effusion is present or by surgical exposure of the pericardium.
      Techniques are now being developed to instrument the normal pericardium. This
      development will allow clinicians and investigators to study pericardial fluid in
      health and in a variety of disorders not associated with pericardial effusion. It
      will also be possible to improve our knowledge of pericardial pressure and the
      pericardial restraints on the heart.

PMID- 9929761
TI  - Therapeutic myocardial angiogenesis using percutaneous intrapericardial drug
      delivery.
AB  - In this manuscript, we describe the potential role of the pericardial space as a
      drug delivery reservoir to administer angiogenic agents to the heart resulting in
      functionally significant angiogenesis with single bolus basic fibroblast growth
      factor (bFGF) delivery. We also describe a percutaneous subxyphoid pericardial
      access technique that is safe, rapid, and reliable.

PMID- 9929762
TI  - Pharmacokinetics and consistency of pericardial delivery directed to coronary
      arteries: direct comparison with endoluminal delivery.
AB  - BACKGROUND AND HYPOTHESIS: Pharmacologic modulation of the contents of the
      pericardial space has been shown to influence the response of coronary arteries
      to balloon injury. Endoluminal (EL) local delivery of various drugs into
      coronaries has been found to be limited by short residence time, as well as by
      highly variable deposited agent concentration. We hypothesized that compounds
      placed into the pericardial space (P) would penetrate into coronary tissue with
      greater consistency than seen after EL delivery and provide for prolonged
      coronary exposure to agents. METHODS AND RESULTS: 125I-labeled basic fibroblast
      growth factor (bFGF), platelet-derived growth factor (PDGF), albumin, or 131I
      labeled diazeniumdiolated albumin (NONO-albumin) were delivered as
      model/therapeutic proteins into the porcine pericardial space (n = 15 pigs) or
      into coronaries using an EL delivery catheter (n = 48 arteries). In subjects
      receiving 125I-labeled proteins, the delivery target or mid-regions of the left
      anterior descending (LAD) and left circumflex (LCx) arteries were harvested at 1
      h or 24 h for gamma-counting and autoradiography, and fractional intramural
      delivery (FID) or retention measured as percent agent in 100 mg artery/agent in
      infusate for both time points. In the animals receiving 131I-labeled NONO
      albumin, serial gamma imaging was employed to evaluate the rate of redistribution
      in individual animals following either pericardial or endoluminal delivery. At 1
      h, FID values ranged from 0.00064 to 0.0052% for P delivery (median 0.0022%), and
      from 0.00021 to 6.7 for EL delivery (median 0.27%). At 24 h, FID values ranged
      from 0.00011 to 0.003 for P delivery (median 0.0013), and from 0.0002 to 1.4 for
      EL delivery. The estimated T1/2 for bFGF redistribution from the vascular tissue
      was 22 h (P) and 7 h (EL), respectively, while the directly determined T1/2
      values for NONO-albumin redistribution from the delivery region were 22.2 h (P)
      and 2.5 h (EL). CONCLUSIONS: These data show that pericardial fluid contents can
      access coronary arteries with intramural concentrations which typically vary by
      10-15-fold, while EL delivery results in a remarkably wide intramural
      concentration range with up to 33,000-fold variability. The apparent
      redistribution rate is more rapid following EL delivery, possibly due to
      sustained diffusive tissue loading from the pericardial space. Pericardial
      delivery appears to offer substantial advantages over EL administration with
      respect to residence time and reproducibility.

PMID- 9929763
TI  - Intrapericardial treatment of inflammatory and neoplastic pericarditis guided by
      pericardioscopy and epicardial biopsy--results from a pilot study.
AB  - From a registry of 136 patients undergoing pericardiocentesis, 14 patients with
      autoimmune and 15 patients with neoplastic effusions were selected. All underwent
      pericardioscopy, epicardial and pericardial biopsy with histologic,
      immunohistologic, and polymerase chain reaction/or in situ hybridization analysis
      for microbial DNAs and RNA. Pericardioscopy identified neoplastic effusions by
      the high occurrence of protrusions. Fibrin threads and layers and
      neovascularization were found in both groups. For identification of the
      inflammatory and neoplastic process, the combined analysis of the cytology of the
      effusion and epicardial biopsy evaluation proved to be most important. Epicardial
      biopsy demonstrated a slightly higher sensitivity for identifying neoplastic
      disorders in the pericardium than cytology alone. Pericardial biopsy was
      inconclusive. Intrapericardial administration of 1 g of crystalloid triamcinolone
      in autoreactive pericarditis prevented recurrence in 13 of the 14 cases after 3
      months and in 12 of the 14 cases after 1 year. In neoplastic effusion,
      intrapericardial administration of 50 mg cis-platin for 24 h prevented recurrence
      of a hemodynamically relevant effusion after 3 months in all, and after 6-12
      months in 14 of 15 patients. Mortality in neoplastic effusion due to noncardiac
      tumor progression was 47 and 80%, respectively, after 3 and 6 months, as can be
      expected in endstage neoplastic disease. This pilot study demonstrates that local
      drug application is feasible, life-saving, and well tolerated by the patients. It
      opens perspectives for local drug application in other cardiac disorders as well.

PMID- 9929764
TI  - Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral
      vectors.
AB  - Adenoviral vectors are promising agents for a number of in vivo gene therapy
      applications including diseases of the heart and coronary vessels. Efficient
      intravascular gene transfer to specific sites has been achieved in occluded
      vessels, but otherwise is hampered by the effect of blood flow on localized
      vector uptake in the vessel wall. An alternative delivery approach to coronary
      arteries is the expression of diffusible gene products into the pericardial space
      surrounding the heart and coronary arteries. However, in vivo pericardial access
      is comparatively difficult and has been limited to surgical approaches. We
      hypothesized that efficient adenovirus-mediated gene expression in pericardial
      lining mesothelium could be achieved by transmyocardial vector delivery to the
      pericardium. To evaluate this concept, a hollow, helical-tipped penetrating
      catheter was used to deliver vector-containing fluid directly into the
      intrapericardial space. The catheter was introduced percutaneously in
      anesthetized mongrel dogs, advanced into the right ventricle, and the tip passed
      through the apical right ventricular myocardium under direct radiographic
      visualization until the open end of the catheter tip resided in the
      intrapericardial space. Adenoviral vectors expressing either nuclear-localizing
      beta-galactosidase, cytoplasmic luciferase, or secreted human alpha 1AT reporters
      (Av1nBg, Av1Lu, or Av1Aa, respectively) were instilled through the catheter into
      the intrapericardial space. Three days later the animals were sacrificed and
      reporter gene expression was evaluated in pericardium, epicardium, and multiple
      other tissues. In animals receiving Av1nBg, beta-galactosidase activity was
      evident in most of the pericardial lining endothelium, up to 100% in many areas.
      In animals receiving Av1Lu, luciferase reporter activity was abundant in
      pericardial tissues, but near-background levels were observed in other organs. In
      animals receiving Av1Aa, human alpha 1AT was abundant (16-29 mg/ml) in
      pericardial fluid, but was undetectable in serum. All animals tolerated the
      procedure well with no electrocardiographic changes and no clinical sequelae.
      These observations demonstrate highly efficient adenovirus vector delivery and
      gene transfer and expression in the pericardium and support the feasibility of
      localized gene therapy via catheter-based pericardial approaches. We suggest that
      the pericardial sac may serve as a sustained-release protein delivery system for
      the generation of desired gene products or their metabolites for diffusion into
      the epicardial region.

PMID- 9929765
TI  - Initial clinical experience with PerDUCER device: promising new tool in the
      diagnosis and treatment of pericardial disease.
AB  - BACKGROUND: The idea to enter the normal pericardial sac safely was unrealistic
      until recently. The development of a novel instrument (PerDUCER pericardial
      access device) for percutaneous access to the pericardium could potentially have
      a significant impact, not only on patients with pericardial diseases but even
      more, or primarily, on diagnosis and treatment of myocardial and coronary disease
      and arrhythmias. HYPOTHESIS: The overall objective of the present study was to
      evaluate the feasibility and safety of the percutaneous pericardial access with
      PerDUCER in patients with pericardial disease, and to analyze our initial
      experience with this new technique, with particular emphasis on sequential
      procedural steps. METHODS: The device was studied in five patients with
      pericardial disease (two men, mean age 50.4 years, range 30-68, four with normal
      body mass index). The procedure consists of two distinct techniques: (1) access
      to the mediastinal space, and (2) pericardial capture, puncture, and insertion of
      the guidewire. Access to the mediastinal space includes the introduction of a
      blunt cannula, a 0.038 guidewire, a dilator-introducer sheath set, and insertion
      of the PerDUCER device. Key points of the PerDUCER procedure are as follows:
      introduction of the blunt cannula without resistance, placement of the dilator
      introducer sheath at the upper third of the heart, systolic movements of the
      PerDUCER device, successful vacuum and capture of pericardium, puncture and
      introduction of the intrapericardial guidewire. RESULTS: Access to the
      mediastinal space was accomplished in four of five patients, as were pericardial
      capture and probably puncture. However, despite numerous successful captures and
      probably punctures of pericardium, we were not able to confirm introduction of
      the intrapericardial guidewire into the pericardial cavity in any of our patients
      (0/5). The procedure was very well tolerated in all patients (5/5). No major
      complications developed during the procedure, bearing in mind that the
      intrapericardial placement of the guidewire was not achieved. Minor complications
      included pain at the dilator-introducer sheath entry site (5/5) and mild
      transient fever (2/5). CONCLUSIONS: According to the present experience, we
      believe that, with minor modifications, the PerDUCER device could be successfully
      implemented for pericardial entry in patients with pericardial disease. Further
      studies are needed to evaluate the feasibility and safety of this new instrument
      in patients with a normal pericardium. This could open a most exciting spectrum
      of possible implementations of the device in the future.

PMID- 9929767
TI  - Establishment of a clinically correlated human pericardial fluid bank: evaluation
      of intrapericardial diagnostic potential.
AB  - The development of a clinically correlated human pericardial fluid bank and
      database is described. A unique feature of this registry is the availability of a
      large number of pericardial fluid samples for testing with respect to multiple
      factors and for correlation with angiographic findings and clinical syndromes
      expressed by the patients. The collection of data at the present time comprises
      frozen pericardial fluid samples obtained from patients who have undergone
      cardiac surgery; and historical, clinical, and laboratory data obtained from the
      patient records. Nearly 400 samples have been stored and analyzed thus far, with
      sample entry continuing. This registry is designed to evaluate the local factors
      that play a role in mediating or reflecting myocardial or coronary responses.
      Pathophysiologic processes of particular interest include restenosis, plaque
      ruptures, and angiogenesis. Study of the pericardial fluid bank should lead to
      enhanced understanding of molecular mechanisms, as well as to the explanation for
      the reasons underlying interpatient variability in these processes. It is further
      anticipated that this information might provide a foundation for the diagnostic
      use of pericardial fluid to individualize therapies targeting angiogenesis or
      plaque physiology.

PMID- 9929766
TI  - Minimally invasive access of the normal pericardium: initial clinical experience
      with a novel device.
AB  - The pericardial space is being investigated as a reservoir for local drug
      delivery to the heart and coronary arteries. Intrapericardial drug delivery is
      currently limited because the pericardial space is normally small and difficult
      to access by standard pericardiocentesis without invasive surgery or risk of
      cardiac injury. Clinical trials are being conducted to evaluate a novel,
      minimally invasive, pericardial access device (PerDUCER, Comedicus Inc., Columbia
      Heights, Minn.). As of October 26, 1998, 12 clinical trials have been completed
      on patients undergoing cardiac surgical procedures. In all patients, a stab
      incision was made 1" subxiphoid and a 17G angled cannula, with preloaded
      guidewire, was advanced into the mediastinal space. After cannula removal, a 19F
      sheath/dilator was inserted over the wire. In eight patients, a median sternotomy
      was performed and the position of the sheath over the anterior pericardium (PC)
      was visually verified. Four patients underwent a closed-chest, fluoroscopy
      assisted procedure. In all patients, the PerDUCER was inserted into the chest,
      via the sheath, and positioned over the PC. The PC was captured by suction and a
      bleb was formed within a side-hole on the PerDUCER tip. A sheathed needle was
      advanced, puncturing the isolated bleb of PC. A guidewire was advanced through
      the needle into the pericardial space and the PerDUCER was removed. Guidewire
      insertion was successful in 10 patients (7 on first attempt, 3 on second) without
      adverse hemodynamic effects or arrhythmia. Other than the guidewire insertion
      site, there was no evidence of injury to the PC or the heart. These initial
      clinical trials suggest that the PerDUCER may provide safe, rapid and effective
      percutaneous insertion of a guidewire into the normal pericardial space.

PMID- 9929768
TI  - The neurologic examination of the podiatric patient.
AB  - This article discusses the techniques and logic of the lower extremity evaluation
      of patients with possible neuromuscular disorders. Its emphasis is on the
      efficient development of a clinical database from which to draw inferences to
      probable pathologic diagnoses. As such, this article provides review material for
      the articles elsewhere in this issue regarding specialized examination
      techniques, differential diagnosis, and specific pathologies.

PMID- 9929769
TI  - A non-neurologist's guide to understanding the EMG/NCV report.
AB  - Podiatrists often refer patients to electromyographers to determine the cause of
      pain, tingling, numbness, and other paresthesias of unknown cause. Hence, some
      knowledge of the study and an understanding that it is an extension of the
      patient's history and physical examination is imperative. To enhance the
      podiatrist's understanding of electromyography, a review of basic
      neurophysiology, the neurologic examination, and electromyography/nerve
      conduction velocities (EMG/NCV) are discussed. Definitions are provided for the
      terms introduced in the article.

PMID- 9929770
TI  - Sensory examination. Comparison of instruments.
AB  - Quantitative sensory testing techniques have been developed to yield more
      consistent and objective measures of sensory deficits than can be obtained
      through the traditional clinical evaluation of the patient. At the same time,
      these measures are less invasive and uncomfortable than typical
      electrophysiologic studies. This article provides an overview of the principles
      of quantitative sensory testing, and discusses currently available instruments.

PMID- 9929771
TI  - Neurologic differential diagnosis in podiatry.
AB  - This article is an overview of a variety of neurologic disorders that a
      podiatrist may encounter. Obviously, the topic is broad. A method of forming a
      differential diagnosis is attempted, rather than generating a list of disorders.
      To make a diagnosis, neurologists identify the affected area of the nervous
      system, then generate a differential diagnosis of the disorders that cause
      disease in that location. The reader is referred to general neurology textbooks
      for further details. A brief review of the anatomy of the nervous system
      clarifies the origin of neurologic symptoms. Common neurologic symptoms and signs
      are discussed. The presentation of diseases that occur in specific systems,
      including lesions of the muscle, neuromuscular junction, nerve, plexus, nerve
      roots, anterior horn cells, spinal cord, and brain, are also described.

PMID- 9929772
TI  - Diagnostic algorithms for neuromuscular diseases.
AB  - Neuromuscular disorders can impose significant disability in patients by virtue
      of weakness, pain, and sensory and autonomic symptoms and deficits. For all of
      these disorders, supportive measures, appropriate physical therapy, and
      respiratory support are beneficial. Pain management can be accomplished by the
      use of antiepileptic medications, such as carbamazepine, phenytoin, valproic, and
      gabapentin. Tricyclic antidepressants can also be helpful for pain management and
      depression. Benzodiazepines and baclofen are helpful for management of
      spasticity. No specific treatment exists yet for the motor neuron disorders. In
      peripheral neuropathies, identifying and treating the cause is most important. In
      other neuropathies, such as in acute or chronic inflammatory demyelinating
      neuropathies, immunosuppression is indicated. Myasthenia gravis can be treated
      with cholinesterase inhibitors and immunosuppression. A specific treatment does
      not exist yet for muscular dystrophies. Immunosuppression is helpful in patients
      with inflammatory myopathies. Toxic myopathies can be treated by removing the
      causative agent and by supportive measures. Endocrine myopathies will respond to
      treatment of the primary endocrinopathy.

PMID- 9929773
TI  - Peripheral neuropathy.
AB  - Diabetes mellitus is the most common cause of peripheral neuropathy in the
      western world. There are many other causes of peripheral neuropathy, and a
      systematic approach (i.e., clinical, electrophysiologic, biochemical, and
      histologic) may be necessary to ascertain the underlying cause. Of paramount
      importance, irrespective of the cause, is the prevention of insensitive foot
      ulceration and foot deformity.

PMID- 9929774
TI  - Compression and entrapment neuropathies of the lower extremity.
AB  - Injury to a peripheral nerve from pressure placed on it causes a compression
      neuropathy. There are particular anatomic sites where individual nerves are most
      vulnerable. The authors describe the physiology and structural anatomy of
      peripheral nerves, the pathophysiology of nerve entrapment, and the
      classification of peripheral nerve injury. Specific compression and entrapment
      neuropathies of the lower extremity are described in detail.

PMID- 9929775
TI  - Movement disorders.
AB  - Movement disorders cause difficulty with ambulation. Hypokinetic disorders
      produce a slow gait with short strides and impairment of balance. The
      hyperkinetic disorders are also marked by an impairment of balance, caused by
      rapid or uncontrollable movements of the limbs or trunk, that interferes with the
      normal rhythm of walking. The gaits of different movement disorders help the
      clinician to classify them. Appropriate diagnosis and treatment of the disorder
      may significantly improve ambulation and quality of life.

PMID- 9929776
TI  - Gait disorders.
AB  - Normal gait requires the dynamic integration of central and peripheral nervous
      systems acting on an intact musculoskeletal framework. A number of specific
      disease processes, as well as aging, may compromise this interaction. Despite the
      complexity of human gait, most common gait disorders can be identified by the
      experienced clinician, using the fundamental tools of history and physical
      examination.

PMID- 9929777
TI  - Orthoses used in the management of neurologic and muscular disorders.
AB  - An anatomic classification for lower extremity bracing is presented, along with a
      review of brace components and their use in the treatment of neurologic or
      muscular disorders. An approach to bracing that employs the concepts of balance
      and flexibility has been suggested rather than rigid formulas calculated from
      poorly defined or established neutral positions for the various affected joints.
      A team-management approach, including a podiatric, osteopathic, and allopathic
      physician, therapist, orthotist, and pedorthist, is always recommended to prevent
      confusion and reduce unnecessary expenses often incurred when different
      disciplines are involved in the treatment of complex neuromusculoskeletal
      disorders.

PMID- 9929778
TI  - Peripheral nerve surgery of the foot and ankle. A review of current principles.
AB  - Planning for peripheral nerve surgery requires consideration of a multitude of
      factors, as well as a surgeon's meticulous skill and experience. With so little
      room for error, every advantage must be taken to optimize repair. Peripheral
      nerve surgery of the foot and ankle is an underappreciated area of neurosurgery
      with comparatively limited published reports and data. The authors reviewed the
      current trends in the surgical management of peripheral nerve injuries of the
      foot and ankle in the hope that an understanding of the basic principles involved
      will allow for future study of the results of such surgery by more surgeons who
      deal with these problems.

PMID- 9929779
TI  - [Is the replicon model applicable to higher eukaryotes?].
AB  - Thirty-five years ago, the Replicon model was proposed by Jacob, Brenner and
      Cuzin to explain the regulation of the Escherichia coli DNA replication. In this
      model, a genetic element, the replicator, would function as a target for a
      positive-acting initiator protein to drive the initiation of replication. This
      simple idea has been extremely useful in providing a framework to explain how the
      initiation of DNA replication occurs in all organisms. The identification of
      autonomously replicating sequences (ARSs) in budding yeast was the first
      extension of the Replicon model to eukaryotic chromosomes. In the higher
      eukaryotes, many biochemically defined replication start sites have been
      identified; nevertheless there is little genetic data indicating that these sites
      contain DNA sequences that are essential for replication. Moreover, in early
      Xenopus or Drosophila embryos, specific DNA sequences are not required either for
      initiating DNA replication or for preventing rereplication within a single cell
      cycle. This apparently fundamental difference between replicators in yeast and
      metazoan embryos may be more superficial than initially thought. In fact, during
      the past several years, an eukaryotic initiator conserved from yeast to man and
      also present in embryonic cells, the origin recognition complex (ORC), has been
      characterized, suggesting that the initiation mechanism should be essentially the
      same in prokaryotes and eukaryotes. In addition, the efficient once-per-cell
      cycle replication of DNA is ensured in eukaryotes by a simple two-step mechanism
      in which the assembly of stable prereplicative complexes (PreRCs) at origins
      precedes and is temporally separated from the firing of these origins. Regulation
      of this process by cyclin-dependent kinases ensures that when origins fire, the
      cell is no longer competent to form new PreRCs. Now, it is important to
      understand how these complexes are remodeled or disassembled during replication
      initiation to trigger the transition from a stable origin-bound complex to a
      mobile replication machine.

PMID- 9929780
TI  - Decreased number of nucleolar organizing regions in collagen lattice cultured
      fibroblasts.
AB  - Dermal fibroblasts cultivated in tridimensional matrices (lattices) of collagen
      exhibit a very low metabolic activity, and a low protein synthesis in particular.
      We have previously shown that ribosomal RNA content and half-life were decreased
      in collagen lattice cultured fibroblasts when compared to monolayer cultured
      fibroblasts. In this study, we seeded fibroblasts in collagen lattices and
      investigated the influence of matrix on the number of nucleolar organizing
      regions. We found that fibroblasts in fully retracted lattices exhibited a
      significant decrease of 45% (P < 0.001) in the number of nucleolar organizing
      regions when compared to monolayer cultured fibroblasts. This decrease was
      correlated to the decrease in ribosomal RNA content. These data suggest that
      extracellular matrix induces early alterations of synthesis and/or processing of
      ribosomal RNAs, explaining, at least partly, the resulting low metabolic
      activity.

PMID- 9929781
TI  - Effects of insulin deficiency on lipoproteins and their hepatic receptors in Rico
      rats.
AB  - The present study was designed to examine the effect of streptozotocin (STZ)
      induced diabetes on the plasma lipoprotein profile and hepatic expression of the
      LDL receptor and HDL binding protein (HB2) in hypercholesterolemic Rico rats. The
      plasma level of HDL1 (density range 1.040-1.063), which is particularly high in
      this rat strain, decreased (-25%) 28 d after STZ administration (50 mg/kg). In
      contrast, the treatment increased (+54%) the plasma concentration of HDL2
      (density range 1.063-1.210). These variations in the lipoprotein concentrations
      were associated with inverse changes in the hepatic protein levels of the LDL
      receptor (+118%) and HB2 (-46%). These results suggest that the hepatic
      expression of HB2, a putative HDL receptor, can influence the plasma level of apo
      Al-rich HDL as has already been shown for the LDL receptor for apo B/E containing
      lipoproteins.

PMID- 9929782
TI  - Neuropathogenesis of HIV-1 infection. Outstanding questions.
AB  - Significant progress in understanding and treating acquired immunodeficiency
      syndrome (AIDS) has been made over the last 5 years. Current multi drug therapies
      prolong patients' lives and reduce the incidence of neurobehavioural symptoms.
      However, the impact of therapy on human immunodeficiency virus type one (HIV-1),
      the causative agent of AIDS, in the brain, is unknown. Some patients develop
      dementia in spite of the multi drug therapies and others develop subtle
      neurobehavioural changes that diminish the quality of their prolonged lives.
      Thus, HIV-1 infection of the central nervous system remains an important clinical
      concern. Although much is known about neuropathology of HIV-1 infection, major
      questions about neuropathogenesis remain. How does HIV-1 reach the brain? Is it
      present in neurons and glial cells? What is the biological and therapeutic
      significance of neurotropism of HIV-1? What causes neuronal damage and loss? And,
      is CNS a reservoir of HIV-1? More research in vivo and in situ in humans and in
      animals, is needed to answer these outstanding questions. Specific experiments
      addressing these questions are proposed.

PMID- 9929783
TI  - Pain. A prelude.
AB  - Although pain is a common fear to most, our overall ability to recognize pain,
      and assess and intervene with appropriate therapies is mediocre at best. However,
      if made a priority, substantial gains can be made in improving patient
      satisfaction with pain control and in rectifying deficits in the knowledge of
      health-care professionals. This goal is not easily obtained and generally
      requires time, patience, and a multidisciplinary team approach. Pain can induce
      numerous metabolic and neuroendocrine responses. While seemingly homeostatic,
      these changes can have significant physiologic and sometimes adverse
      consequences. Anesthesia and analgesia, especially by way of neural blockade, can
      alleviate some of the changes and sometimes improve unwanted consequences. While
      at times these techniques have not significantly altered outcome, at other times
      significant benefits have been observed. More sophisticated techniques and
      pharmacotherapies are being developed and introduced with increased frequency,
      but alone they will probably have only minimal impact on overall morbidity and
      mortality. The integration of a multimodal approach seems logical in the critical
      care setting, with analgesia as the cornerstone.

PMID- 9929784
TI  - The stress response of critical illness.
AB  - The integrated stress response to tissue trauma is crucial for the maintenance of
      homeostasis. An exaggerated or prolonged response may be detrimental in
      compromised patients. Knowledge of the involved afferent pathways will suggest
      therapeutic interventions that may modulate the intensity of the stress response.
      Described are these concepts as they relate to perioperative medicine.

PMID- 9929785
TI  - Evaluation of pain in the critically ill patient.
AB  - This article reviews the evaluation of pain in critically ill patients of all
      ages. Sources of pain and its physiologic significance are discussed. Factors
      influencing pain, perception, and behavior are also addressed to broaden health
      care professionals' vision of the difficulties associated with accurate pain
      assessment. The evaluation process, including a discussion of several tools
      ranging from visual analog scales to bispectral analysis, as well as goals of
      therapy are discussed. Finally, a practical approach to the assessment process,
      which supports the need for established, regularly used evaluation and treatment
      protocols, is proposed.

PMID- 9929787
TI  - Regional anesthesia techniques for pain control in the intensive care unit.
AB  - The judicious use of regional anesthesia in the intensive care unit should
      improve patient comfort. Techniques covered include intercostal nerve blocks,
      interpleural blocks, paravertebral blocks, brachial plexus blocks, and femoral
      nerve blocks. Rational patient selection for each technique mentioned is also
      discussed.

PMID- 9929786
TI  - Pharmacokinetic considerations.
AB  - Limited studies of the pharmacokinetics of pain medication suggest altered serum
      elimination when the liver is hypoperfused or affected by severe cirrhosis. Drugs
      that are eliminated by Phase I oxidation reactions are sensitive to changes in
      hepatic blood flow, while drugs eliminated by Phase II glucuronidation are more
      affected by diseased hepatocytes. Additionally, alterations in renal function
      decrease elimination of both parent drugs and metabolites, resulting in toxicity
      for selected opioids such as meperidine and morphine. Caution is suggested in
      drawing general conclusions from pharmacokinetic patterns of opioid elimination
      discussed in this review. Practitioners should be aware that drugs with short
      duration of action may have long half-lives and accumulate in end-stage liver and
      renal disease. While pharmacokinetic differences have been described in various
      populations, the clinical effects and adverse outcomes are greatly influenced by
      numerous independent physiologic alterations seen in critical care patients.
      Patients with severe alterations in liver and renal function should be
      administered pain medications judiciously because these patients are predisposed
      to metabolic disarrays. These patients should not be denied pain care, but they
      may benefit from smaller, less frequently administered doses, rather than
      continuous infusion of opioid drugs. Titration of doses to clinical effects with
      careful patient assessment for adverse effects is crucial for achieving desired
      therapeutic outcomes with analgesic agents in the ICU.

PMID- 9929788
TI  - Intravenous analgesia.
AB  - Pain and its treatment are known to have adverse effects on the organism,
      including deterioration in myocardial, diaphragmatic, and small bowel function.
      The provision of adequate intravenous analgesia, and the choice of agent, can
      ameliorate or exacerbate these manifestations of the stress response. The choice
      of agent, opioid or non-opioid, has in some respects become more difficult as
      more information has become available regarding the merits and adverse effects of
      each. Increased awareness of the frequency of hypoxemia secondary to the opioids'
      ability to cause an obstructive sleep apnea picture, and the cost efficiency of
      ketorolac through a reduction in opioid toxicity, contrast with recent studies
      which suggest that the gastrotoxic and nephrotoxic effects of ketorolac may occur
      earlier than previously suspected. The suitability of using the dissociative
      anesthetic agent ketamine in critically ill patients remains to be proven.
      Ketamine provides intense analgesia at subanesthetic doses. Its centrally
      mediated sympathomimetic action encourages hemodynamic stability, and it is
      relatively devoid of respiratory depressant activity. Increasing experience with
      ketamine outside the operating room has resulted in its successful use in cases
      of severe bronchospasm and status epilepticus.

PMID- 9929789
TI  - Intrathecal and epidural analgesia.
AB  - Centroneuraxis analgesia has a place in the management of critically ill
      patients. With the safety of the intrathecally placed microcatheter now in
      question, epidural blockade is more suitable in the intensive care unit setting.
      The different mechanisms of action and the resultant synergy of local anesthetic
      agents and opioids, as well as their different side effects, are outlined. The
      contraindications to neuraxial blockade are discussed, and the role of epidural
      analgesia in the management of flail chest syndrome is addressed in detail.

PMID- 9929790
TI  - Adjuncts to analgesia. Sedation and neuromuscular blockade.
AB  - This article provides an overview of some of the current issues involved in
      sedation and anxiolysis in the intensive care unit. The problems involved in
      trying to monitor sedation levels are discussed, as are some of the newer options
      available for physiologic monitoring of the central nervous system. The problem
      of abnormal mental states in the intensive care unit and the range of
      antidepressant therapy now available are also covered. The importance of sleep
      deprivation and the properties of the neuromuscular blockers are also discussed.

PMID- 9929791
TI  - The acute pain service.
AB  - The often inadequate treatment of acute pain is more often due to improper
      application of available therapies than to the unavailability of effective drugs
      and techniques. In our institution, the establishment of an acute pain service
      has improved the safety and efficacy of postoperative pain control. This has been
      achieved not simply through the immediate availability of a group of specialist
      physicians and nurses, but also through staff education. The latter has addressed
      many of the misconceptions preventing proper and safe use of potent analgesic
      agents. Although provision of intravenously administered patient-controlled
      analgesia appears not to influence patient outcome, it can result in improved
      analgesia and patient satisfaction when used properly. Epidurally administered
      patient-controlled analgesia, on the other hand, appears to provide superior
      relief of activity pain and earlier resolution of postoperative ileus. The
      administration of local anesthetic agents, in particular, may reduce reflex
      diaphragmatic dysfunction following thoracoabdominal surgery and decrease the
      incidence of graft occlusion following lower extremity vascular procedures.
      Epidural catheter placement, however, is not without risk, especially in subjects
      with an established or potential coagulopathy.

PMID- 9929792
TI  - Pain management and pulmonary dysfunction.
AB  - This article examines the extent to which pain contributes to pulmonary
      dysfunction in burns, trauma, a variety of acute abdominal diseases, and
      postoperatively. Also discussed are the options available to attenuate the extent
      of this contribution.

PMID- 9929793
TI  - Analgesia for trauma and burns.
AB  - This article has described the physiologic impact of trauma- and burn-related
      pain as well as the effect of a clinician's choice of analgesic method, using the
      specific example of regional analgesia for pain caused by chest trauma. It has
      been observed that trauma exerts a holistic influence upon the organism,
      marshalling reflexes, multi-system physiologic stress responses, and psychologic
      responses--some adaptive and others maladaptive. There is reason to consider that
      timely analgesia can intervene in this dynamic process and interdict the
      establishment of a debilitated state. A key finding of these studies is that a
      report of pain relief may not be the best outcome measure since the choice of
      analgesic method(s) has a significant impact on the secondary effects of pain.
      Although extrapolated from studies of perioperative pain, findings do suggest
      that there may be a critical period of time during which the secondary effects of
      a painful stimulus may be attenuated or reversed. How long this period of
      reversibility exists has not been determined, so planning for the level and goals
      of analgesia intervention should occur early on. Analgesia should be viewed not
      only as a humanitarian gesture, but also a therapeutic maneuver with the goal
      being the early restoration of function and the mitigation of a chronic
      debilitated state. There is scattered evidence that regional analgesic techniques
      using local anesthetics have some advantages over other analgesic modalities,
      particularly in the trauma patient with pulmonary compromise; however, as with
      other medical interventions, one should develop a strategic plan of application
      which includes consideration of potential complications and side effects, in
      addition to the potential therapeutic effects. The traumatized body, as well as
      the attending physician, must deal with inflammation, the neurohumoral reaction,
      musculoskeletal reflex responses, and numerous other reactions designed to
      stabilize an acutely destabilized systemic entity. Multimodal analgesia, with the
      balanced use of systemic and regional medications, has given the best short- and
      long-term results in studies of postthoracotomy pain. The use of a similar
      combined plan for posttraumatic analgesia seems logical; however, many questions
      remain as yet unanswered. In particular, what are the optimal combinations of
      techniques/medications to employ to maximize analgesia and minimize secondary
      effects of trauma? Can an aggressive multimodal approach intervene effectively in
      the development of chronic pain states, and if so, for how long? What are the
      long-term benefits to be derived from making a significant impact on the stress
      response? Last, but not least, can analgesic interventions be shown to be cost
      effective according to current societal pressures to reduce the cost of health
      care? These and other questions are not easy to answer. Trauma strikes, in a
      variable fashion, patients of all ages, with all forms of comorbidity, and is
      treated by a technology that continues to evolve. Previous research related to
      the effects of analgesic treatments has been hampered by the limitations that
      arise when isolated groups embark on vast projects with limited numbers of
      patients available. It is time for investigators at multiple centers to embark on
      coordinated efforts to address long-term questions related to trauma and the
      therapeutic efficacy of analgesia.

PMID- 9929794
TI  - Pain management in the pediatric intensive care unit.
AB  - Control of pain in the pediatric intensive care unit has become increasingly
      important to intensivists. Improved understanding of the pharmacology of
      analgesics and the development of new techniques for analgesic administration
      have greatly enhanced the ability of intensivists to successfully manage patients
      in pain. The appropriate selection, use, and techniques for administration of
      analgesics in the treatment of pain in pediatric patients are discussed.

PMID- 9929795
TI  - Pain management in the critically ill obstetric patient.
AB  - Safe and successful pain management in pregnant women requires an understanding
      of the normal physiologic changes of pregnancy. Some hemodynamic changes of labor
      and delivery are attenuated by effective epidural analgesia. The ideal analgesic
      agent for laboring parturients should produce a rapid onset of analgesia that
      lasts throughout labor without any adverse effect on the mother or fetus. There
      is no ideal analgesic for pain relief in labor. The physiologic changes of labor
      and delivery are reviewed, together with commonly used analgesic techniques.
      Special emphasis is placed on critically ill obstetric patients with concomitant
      cardiac disease.

PMID- 9929796
TI  - Clinical rationale for tooth stabilization and splinting.
AB  - Tooth mobility can be a consequence of periodontal inflammation, attachment loss,
      and occlusal trauma. At times, this mobility may be tolerable, whereas at other
      times mobility may contribute to occlusal instability and/or patient discomfort.
      This article describes the clinical rationale for and the effects of splinting
      mobile teeth.

PMID- 9929798
TI  - Periodontal trauma and mobility. Diagnosis and treatment planning.
AB  - With the dearth of well-controlled human clinical studies, it is still impossible
      to answer the question of whether occlusal trauma modifies the progression of
      attachment loss resulting from inflammatory periodontal disease and the companion
      questions related to the treatment of occlusal trauma and mobility. Teeth with
      stable mobility are apparently at no greater risk of attachment loss than
      nonmobile teeth. Increasing mobility is a concern that must be addressed by
      inflammatory control, occlusal adjustment, and perhaps some type of stabilization
      or splinting of the tooth in question. In addition, greater attachment gains have
      been noted when occlusal adjustment was included as part of surgical therapy.
      There is no question that aspects of occlusal therapy have an empiric base. It is
      incumbent on the clinician to examine for, diagnose, and treat trauma from
      occlusion to stabilize the dentition. Proper occlusal management assists in
      maintaining the patient's natural dentition in a state of health and comfortable
      function.

PMID- 9929797
TI  - Physical behaviors of fiber reinforcement as applied to tooth stabilization.
AB  - This article presents an understanding of the mechanical response of polymer
      matrix composite materials that are reinforced with fibers that have high levels
      of failure strain. Also discussed are the basic principles for the use of the
      materials and techniques to optimize the clinical success for the applications in
      which these fibers are used to restore and maintain form and function to the
      masticatory structures.

PMID- 9929800
TI  - Non-crown and bridge stabilization of severely mobile, periodontally involved
      teeth. A 25-year perspective.
AB  - It is the author's belief, after analyzing forces and stresses on the
      periodontium for more than 30 years, that stabilization of severely mobile teeth
      can retain teeth, if in health, almost indefinitely. Because these teeth are
      retained using restorative materials, recurrent caries is a problem that needs to
      be treated. Tooth loss resulting from caries can occur. In the author's 26 years
      of using extracoronal adhesive resins for splinting, the technology of adhesive
      bonding and restorative resins have been improved. Earlier shortcomings of the
      physical properties of these materials never dissuaded the author from
      recommending splinting. When the cases were presented to the patient and the
      referring dentist, the types of the current materials used to splint teeth were
      immaterial. Realizing that improvements in adhesives and resins would be
      developed, the near-hopeless teeth were retained. Because the elderly population
      is the fastest-growing segment of the population, caries control is more of a
      concern than it was 50 or more years ago. Because teeth are being retained longer
      in this cohort, and because caries has a greater potential to exist, supportive
      periodontal therapy and recalls and caries examination become more important.

PMID- 9929799
TI  - Tooth stabilization and splinting before and after periodontal therapy with fixed
      partial dentures.
AB  - The design and use of fixed partial dentures as a definitive restoration to
      stabilize and splint teeth have been reviewed. The provisionalization of the
      splinted patient has been described as it is incorporated into the treatment plan
      of patients with a weakened periodontium. The current controversy of
      incorporating implants in the patient requiring splinting was discussed, and
      recommendations are made. Dentists are encouraged to explain all potential
      ramifications of splinting with fixed partial dentures, including cost, frequency
      of office visits, and potential alterations or remakes of the prosthesis should
      physiologic demands surpass the capabilities of the remaining teeth.

PMID- 9929801
TI  - New-generation bonded reinforcing materials for anterior periodontal tooth
      stabilization and splinting.
AB  - Teeth are splinted and stabilized in the anterior region for a variety of
      reasons. This article presents the techniques for periodontal splinting with an
      adhesive technique using direct placement ribbon reinforced composite resins. The
      research supporting this technique is also reviewed.

PMID- 9929802
TI  - An innovative pre-impregnated glass fiber for reinforcing composites.
AB  - This article summarized the development of pre-impregnated, fiber-reinforced
      composites. Previous efforts with various reinforcement materials for splinting
      are cited. The benefits of pre-impregnation are explained. The clinical procedure
      for placing a fiber-reinforced composite splint is described.

PMID- 9929803
TI  - Evaluation for tooth stabilization and treatment of traumatized teeth.
AB  - Thorough evaluation and correct treatment of traumatized teeth improve their
      chances for survival. This article provides an overview clinical evaluation and
      how best to treat the tooth that has been traumatized. The rationale and
      techniques for tooth stabilization of the traumatized tooth will also be
      presented.

PMID- 9929804
TI  - Tooth stabilization for orthodontic retention.
AB  - This article reviews stability and retention of the orthodontically treated
      dentition. Factors and conditions that influence post-treatment stability are
      discussed. Methods for stabilizing and retaining the occlusion are reviewed.

PMID- 9929805
TI  - Anterior esthetic considerations when splinting teeth.
AB  - There are many techniques for stabilizing and splinting teeth. No matter which
      restorative technique is chosen, the technical elements of marginal fit,
      psychologic contour, cleansibility, and occlusion must be met. When the
      restoration is in the esthetic zone of the oral cavity, there is an additional
      element of achieving an acceptable cosmetic result. This article presents an
      overview of concepts to achieve acceptable esthetic results when teeth are joined
      together.

PMID- 9929806
TI  - Maintaining the oral health of splinted teeth.
AB  - The combined and concerted efforts of patients and providers in poststabilization
      maintenance promote long-term health for the dental splint and its surrounding
      and supporting soft and hard tissues. Dental splints that are properly placed and
      contoured enable effective patient self-care and contribute to a positive
      prognosis. The provider's role in fabrication, placement, and oral hygiene
      instruction cannot be overemphasized. Professional follow-up concerning
      periodontal and caries risk assessment, periodontal debridement, and needed
      preventive interventions are critical to splint longevity. Continued success
      cannot occur without scrupulous patient self-care. The professional team must
      provide patients with comprehensive oral care instruction. A host of home care
      aids are available to assist patients in effective home care practices. With the
      combination of proficient clinical skill, appropriate dental material selection,
      good communication, and comprehensive health education, both providers and
      patients can benefit from esthetic, functional, and healthy dental splints.

PMID- 9929807
TI  - [The role of neurochemical mechanisms in the pathogenesis of kinetoses and the
      therapeutic-prophylactic action of drugs].
AB  - Experimental and clinical data on the neurochemical and neurohumoral mechanisms
      underlying the pathogenesis and therapeutic and preventive effects of drugs are
      generalized. Literature data and the authors' own data concerning drugs used for
      the prevention and treatment of kinetoses are given. The possible mechanisms of
      their effect against motion sickness are suggested. New ideas of the means of
      search for substances possessing vestibuloprotective activity, and the principles
      of rational pharmacological correction of vestibuloautonomic disorders in motion
      sickness are discussed.

PMID- 9929808
TI  - [The effect of sodium nitroprusside and lamotrigine on D-[3H]aspartate release
      from mouse cortex slices].
AB  - The work deals with the study of the effect of the nitrous oxide and the
      antiepileptic agent lamotridgin on nonstimulated and K(+)- and veratridine
      stimulated release of D-[3H]aspartate from sections of the brain cortex of mice.
      Sodium nitroprusside (0.1 mM) intensified nonstimulated (by 38-52%) and K(+)
      stimulated (by 86%) release of labeled D-aspartate. Lamotridgin (0.1 mM)
      inhibited nonstimulated and veratridine-stimulated release of the label (by 50
      and 70%, respectively). Sodium nitroprusside completely turned the inhibiting
      affect of lamotridgin on spontaneous and veratridine-stimulated release of D
      aspartate. It is suggested that NMDA-subtype presynaptic receptors contribute to
      the regulation of D-aspartate release and are modulated by nitrous oxide.

PMID- 9929809
TI  - [The chronobiological characteristics of the antistressor action of anxiolytic
      agents].
AB  - Agents with anxiolytic properties, namely, the tranquilizer diazepam (0.1 mg/kg),
      melatonin a hormone secreted by the pineal gland (0.1 mg/kg), and the beta
      adrenergic blocker anapriline (5 mg/kg), remove in a similar manner stress
      induced dysrhythmia in rats. Under their effect the circadian rhythm of motor
      activity is normalized and adaptation shifts in the time dynamics of forced
      swimming are encountered.

PMID- 9929810
TI  - [The effect of caffeine on the color-discriminating function of the retina in
      volunteers].
AB  - A low dose (0.2 g) of caffeine had no effect, whereas a high dose (0.4 g) lowered
      the light sensitivity threshold of the eye retina, as determined by campimetry in
      young people.

PMID- 9929811
TI  - [The anti-ischemic properties of new specific bradycardic agents, derivatives of
      2-mercaptobenzimidazole].
AB  - Experiments on narcotized cats demonstrated that the derivatives of 2
      mercaptobenzimidazole possessing the properties of specific bradycardic agents
      and coded as CM-251, CM-266, and CM-345, reduce the mean rise of segment ST on
      numerous leads of the epicardial electrogram during 5-min occlusion of the
      anterior descending branch of the left coronary artery. The agents stabilize the
      heart pumping and contracting functions under conditions of 30- and 60-min
      reperfusion of the coronary artery, respectively. It is concluded on the grounds
      of the obtained data that the 2-mercaptobenzimidazole derivatives possess a
      marked anti-ischemic action.

PMID- 9929812
TI  - [The cardiotoxic properties of kordaron in acute myocardial ischemia and
      infarct].
AB  - Cardiodepressive and arrhythmogenic properties of cordarone were studied on cat
      in conditions of experimental acute ischemia and myocardial infarction upon
      intravenous infusion. The obtained results showed an increase cordarone
      cardiotoxicity and arrhythmogenic properties in conditions of myocardial
      infarction. No reliable difference was observed in dynamics of cordarone-induced
      changes in ECG parameters in animals with myocardial ischemia of various duration
      and intact animals.

PMID- 9929813
TI  - [The search for new anti-ulcer agents from plants in Siberia and the Far East].
AB  - Screening tests on mice with the use of a model of neurogenic damage to the
      stomach revealed antiulcerative activity in extracts of Amoor cork tree, Pacific
      Bergenia, Lespedeza dichromatic, Leuzea carthamoides, sea-buckthorn, common
      aspen, Manchurian nuts, Serratula coronarius, and Scutellaria baicalensis. It was
      proved that an extract of aspen cork produces a marked antiulcerative effect on
      being administered to animals with "acute" ulcers and in treatment of chronic
      peptic ulcer. The study of various drug forms of Serratula coronarius extracts
      (prepared from the bark and the bark and shoots) in experiments on mice
      (neurogenic ulcer) and rats (Aspirin ulcer) revealed the most marked
      gastroprotective effect of oil extracts of bark and shoots. A high
      antiulcerogenic activity of extracts prepared from grass and roots of Scutellaria
      baicalensis was demonstrated.

PMID- 9929814
TI  - [The role of cAMP phosphodiesterase inhibitors in the pharmacotherapy of the
      hypoxic syndrome].
AB  - The authors studied the pharmacotherapeutic activity of drugs belonging to
      various pharmacological groups which are inhibitors of cAMP phosphodiesterase in
      the hypoxic syndrome. The increase in the level of the secondary intermediate of
      the adenylate cyclase path in transmission of the intracellular signal from the
      outer surface of the cell to the nucleus, the hypoxia protector cAMP, under the
      effect of the drugs under study favorably influenced survival and the course of
      hypoxic hypoxia in overheating. A combination of quercetin bioflavonoid with
      acetylsalicylic acid demonstrated stronger antihypoxic and thermoprotector
      properties. The results were less marked with the use of the calcium channel
      blocker cinnarizine and an agent of the xanthine pentoxyfelline group. The
      possible mechanisms of the antihypoxic activity of the drugs under study are
      discussed.

PMID- 9929815
TI  - [Immunity during ampicillin administration against a background of
      immunosuppression].
AB  - The effect of 50 and 100 mg/kg doses of ampicillin, immunocompromised by
      cyclophan and azathioprine, on immunity of intact mice was studied. Ampicillin
      did not change the number of antibody-forming cells (AFC) and delayed
      hypersensitivity (DHS) in immunosuppression. It inhibited spontaneous oxidant
      metabolism of neutrophils and macrophages against the background of azathioprine.
      The therapeutic effect of ampicillin was maintained under such conditions. In
      intact animals the antibiotic did not change the number of AFC, increased DHS
      expression, and reduced the spontaneous index of macrophage activation in the
      nitroblue tetrazolium test.

PMID- 9929816
TI  - [The potential use of an extract of aspen bark for enhancing the efficacy of
      specific treatment methods in experimental malignant neoplasms].
AB  - The effect of liquid aspen bark extract on the effectiveness of cytostatic and
      surgical methods of treatment of experimental tumors in mice was studied. The
      extract was found to raise the antitumorous and antimetastatic effects of the
      above indicated methods of treatment on the tumor process.

PMID- 9929817
TI  - [The morphological and functional status of the ovaries in rats administered
      antitumor preparations].
AB  - Experiments were performed on Wistar rats to evaluate comparatively the
      morphological and functional state of the ovaries in the early and late-term
      periods after a single injection of a platinum-containing cytostatic drug
      platidiam and an antibiotic of the anthracycline series farmorubicin. It was
      found that the antineoplastic agents caused a similar toxic effect on the
      animal's sexual glands. The number of generative elements in the ovaries
      decreased in this case and the duration of the estrous cycle, the indices of
      embryonal death, and the pregnancy index increased.

PMID- 9929818
TI  - [The efficacy of the polyphenol plant preparation piflamin in drug damage to the
      liver].
AB  - The hepatoprotective properties of the flavonoid preparation piflamine of field
      peas grass were studied on a model of experimental paracetamol liver damage.
      Piflamine was found to normalize the parameters of carbohydrate, protein, and
      lipid metabolism, increase the activity of the antioxidant system, and restore
      the processes of bile production and bile secretion. The drug is prospective due
      to its quite cheap and available source of raw materials.

PMID- 9929819
TI  - [The effect of bromantane on the physical work capacity of laboratory animals].
AB  - The positive effect of bromantan (0.5-50 mg/kg) on the efficiency of physical
      work of mice and rats (swimming test, running on a treadmill) exceeds that of
      phenamine administered in optimal doses by 1.3-1.6 times. Such an effect of
      bromantan lasts no less than 24 h. The drug delays decrease of physical
      efficiency and restores it sooner in repeated extreme running loads, prevents in
      rats the corresponding electron-microscopic changes in the cardiomyocyte and
      myocyte mitochondria of the skeletal muscles. The data obtained suggest that the
      positive effect of bromantan on the physical efficiency is associated not only
      with its psychostimulating action but also with the membrane-protecting effect.

PMID- 9929820
TI  - [The role of cytochrome c in preventing postresuscitation functional disorders of
      the central nervous system].
AB  - The effect of intracarotid injection of cytochrome c on the course of the early
      postresuscitation period was studied in experimental animals (albino rats) after
      5-min clinical death from acute blood loss. It was shown that the drug normalizes
      the disturbed metabolic processes in the brain, reduces the structural changes
      consequent upon total ischemia, stabilizes the activity of the cardiovascular
      system and, as a result of this, contributes to restoration of functional
      activity of the central nervous system in the early postresuscitation period.

PMID- 9929821
TI  - [The chemico-pharmacological patterns in the action of plants from the family of
      Pyrolaceae].
AB  - The effect of leaf decoctions of three plants of the Pyrolaceae family, namely,
      umbrella wintergreen, one-side ortilia, and round-leaf Pyrola was studied in rat
      experiments. All plants under study were found to contain approximately equal
      amounts of tannins and arbutin glycoside. Their concentration was comparable
      though rather lower than in common bearberry, a well-known plant with diuretic
      and antiseptic activity. When given for a long time, all Pyrolaceae increased
      urination and sodium excretion. Besides, their decoctions caused an antimicrobial
      effect. Only round-leaf Pyrola weakened the development of experimental
      inflammation. Its anti-inflammatory effect was probably due the presence of
      flavonoids the content of which in Pyrola was maximum.

PMID- 9929822
TI  - [The age-related characteristics of the effect of dimethylsulfoxide on myocardial
      catalase activity in immobilization stress].
AB  - The effect of intraperitoneal injection of dimethyl sulfoxide (DMSO) in a dose of
      175 mg/kg on the catalase activity of the myocardium of adult and old-aged rats
      subjected to immobilization stress was studied. DMSO injection promoted catalase
      activation in the heart of old-aged rats subjected to immobilization and
      practically had no effect on the analogous parameter in adult animals. Together
      with activation of the enzyme, changes occur in it which raise the effectiveness
      of the catalase response under conditions of stimulated production of active
      forms of oxygen in oxidation stress (increased affinity for the substrate, more
      expressed changes in activity in response to a change in pH of the medium,
      limited effect of the inhibitors on the enzyme).

PMID- 9929824
TI  - [Blockade of the ion channels of the skeletal muscle acetylcholine receptor].
AB  - The review deals with the literature data concerned with substances causing an
      effect on the ion channels of acetylcholine receptors in the skeletal muscles:
      local anesthetics, inhalation narcotics, postsynaptic muscle relaxants, and other
      drugs.

PMID- 9929823
TI  - [Current concepts of the structure and functions of retinoid receptors].
AB  - The article discusses the principal structure of nuclear receptors. The structure
      and function of retinoid receptors, their main ligands and inhibitors are
      analysed. Data (experimental and clinical) concerning the immunotropic
      antineoplastic and cardiovascular activity of the main retinoids are given.

PMID- 9929825
TI  - [The clinical pharmacokinetics and metabolism of acetylsalicylic acid. The
      current status of the problem].

PMID- 9929826
TI  - [Design of constructions for the expression of proteolytic antibody light chain].
AB  - A new system for the expression of a catalytic light chain antibody to the
      vasoactive intestinal peptide is described. The system made possible the
      isolation the large amounts of a homogeneous protein without any additional
      peptide domains. The preparation obtained can be used in further experiments on
      light chain crystallization and in X-ray-structural analysis of its catalytic
      center.

PMID- 9929827
TI  - [Further genetic study of tandem duplication formation in the region of the deo
      operon in the process of Escherichia coli K-12 conjugational recombination].
AB  - The formation of heterozygous duplications in the region of the deo operon was
      studied in conjugational matings (male) HfrH deoC deoD thr::Tn9 thyA x HfrH deoA
      deoB::Tn5 thyA. When recombinants that inherited the donor marker thr::Tn9 (Cml
      r) were selected on a medium containing thymine and chloramphenicol, but not
      threonine, more than 80% of the offspring were heterozygous tandem duplications
      extending to the region of the deo operon. In matings with a thymidine-dependent
      HfrH deoA deoB::Tn5 thyA strain as a recipient, when recombinants were selected
      on a medium containing thymine, i.e., under conditions of thymine starvation of
      merozygotes, the recombinogenic effect was observed. However, this effect did not
      change the frequency of duplication formation. The integration of genetic markers
      via homologous recombination into the chromosomal regions adjacent to
      duplications occurred at a lower frequency. An analysis of the formation of
      haploid segregants by duplications showed that, in most cases of duplication
      formation, the proximal segment of the donor chromosome is integrated into the
      distal position, i.e., after the homologous segment of the recipient chromosome.

PMID- 9929828
TI  - [Interaction between three types of variation and fluctuating asymmetry in the
      population of malaria mosquito Anopheles messeae Fall].
AB  - In the population of the malaria mosquito Anopheles messeae, interrelations of
      three types of variation (polymorphism for inversions, dorsal color of abdomen
      and thorax, and number of dents in the crests of the stigmal plate) and
      fluctuating asymmetry were studied. The presence of white pigmentation on the
      larval dorsum did not correlate with inversion polymorphism and fluctuating
      asymmetry, but correlated with the number of small and large dents in the crests
      of stigmal plate. Asymmetry was shown to have a weak positive correlation with
      the number of dents. In larvae having a small number of dents, a decrease in the
      frequency of autosomal homozygotes 3R00 and an increase in the frequency of
      autosomal heterozygotes 3R01 were found. The dents in the crests of the stigmal
      plate had two morphological forms: a large one, which is associated with arms 2R
      and XL, and a small one, which is associated with arms 3R, XL, and 3L.
      Correlation between inversion polymorphism and bilateral (fluctuating) asymmetry
      was more complex. The group of individuals with a difference by one dense
      differed from that with a difference by three or more dents in the frequency of
      chromosome sequences XL0, XL1, and 2R0. Chromosome sequences XL1, 2R0, 3R0, and
      3L1 were classified as those increasing the developmental stability of
      individuals; XL2, XL0, 2R1, 3R1, and 3L0, as those decreasing it.

PMID- 9929829
TI  - [Allozyme variation of lactate dehydrogenase (EC1.1.1.27) in a series of
      vertebrate animals].
AB  - An allozyme variation of loci-encoding lactate dehydrogenase was compared in
      different vertebrate classes. A lower level of heterozygosity in warm-blooded as
      compared to cold-blooded vertebrates was shown. The highest heterozygosity was
      revealed in anurous and caudate amphibians; the lowest, in birds and mammals.
      Fishes and reptiles exhibited an intermediate level of heterozygosity. In higher
      groups of vertebrates, differences in the electrophoretic mobilities between
      alleles decreased. A key aspect of this is a hiatus of these differences in
      fishes and mammals. On the basis of this analysis, the following conclusions may
      be drawn: (1) the rate of amino-acid substitutions in homologous proteins is
      unequal in distant phylogenetic lineages; (2) the level of heterozygosity is
      related to the average amount of electrophoretic allelic differences at the class
      level; (3) significant differences in variation pattern in the phylogenetic
      lineage of vertebrates is probably associated with the evolutionary features of
      the genomic organization of groups at different evolutionary levels.

PMID- 9929830
TI  - [Distribution of T-bands and telomeric (TTAGGG)n nucleotide repeats on
      chromosomes of Bos taurus].
AB  - Distribution of T-bands on mitotic chromosomes of Bos taurus was studied.
      Association of T-bands with telomeres and enrichment of T-bands with genes, with
      a known localization is described. After THA-banding on the chromosomes of
      cattle, telomeric and pericentromeric regions of all autosomes showed bright
      fluorescence. The exception was for chromosome 7, which did not have telomeric T
      bands. Interstitial T-bands were detected only on chromosomes 7, 16, and Y (7q13,
      7q15, 7q22, 7q24, 16q21, and Yp12). A total proportion of centromeric, telomeric,
      and interstitial T-bands was 11.19, 9.97, and 2.02% of the length of the haploid
      chromosome set, respectively. By means of fluorescent in situ hybridization
      (FISH), the presence of the telomeric repeat (TTAGGG)n was shown not only in
      telomeric regions of all autosome, but also in all pericentromeric regions. The
      obtained data are indicative of the specificity of T-banding on the chromosomes
      of Bos taurus.

PMID- 9929831
TI  - [Polymorphism of noncoding regions of the mitochondrial genome in the indigenous
      population of Southeastern Tuva Republic].
AB  - Deletion-insertion polymorphism of the V region and restriction polymorphism of D
      loop for seven restriction enzymes--AspS9I (Cfr3I isoschizomere), BamHI, Bme18I
      (AvaII), EcoRV, HaeIII, KpnI, and Kzo9I (Sau3AI)--in mitochondrial DNA (mt DNA)
      were studied in the indigenous population of southeastern Tuva Republic. The
      results were compared with the data on Russians, Mongols, Buryats, and Altaians.
      Tuvinians significantly differed from Mongols in the frequency of the 9-bp
      deletion of the V region (1.89 and 8.07%, respectively). Additionally,
      significant differences between Tuvinians and samples of Mongols and Russians
      were obtained for frequencies of the AspS9I, HaeIII, and KpnI restriction sites.
      A comparison of the polymorphism of mitochondrial genome in individuals of
      different sexes and ages was performed in the studied sample.

PMID- 9929832
TI  - [Selective structure of the gene pool. III. Technology of determination from
      F(ST)-statistics using numerical resampling].
AB  - The selection pressure on the ith gene was determined on the basis of the
      heterogeneity of interpopulation diversity FST(i), assumpting that the
      significant deviation of FST(i) (observed differentiation of the ith gene) from
      Fe (selectively neutral differentiation) indicates selection. A selectively
      neutral variation Fe was estimated from the mean FST, averaged over the total set
      of genes. Since the validity of the equation FST approximately Fe = (4NeMe + 1)-1
      depends on the fulfillment of conditions of the theoretical model as well as on
      organization of sampling of genes and subpopulations rather than on statistical
      parameters of the gene sample, an additional correction by boot-strapping is
      suggested. Simulation of sampling of the gene pool using numerical resampling
      (10(6) samples from each of the 50 markers) allowed us to characterize the
      selective structure of the gene pool. This structure consists of the following:
      one class of selectively neutral genes, NEUTRAL (FST(i) approximately Fe); and
      two classes of selective genes, LOWER DIFF (FST(i) < Fe) and SUPER DIFF (FST(i) >
      Fe). Interclass regions N-LOWER and N-SUPER between the classes of neutral and
      selective genes were defined with the use of bootstrapping. The hypothesis on the
      presence or absence of selection cannot be formulated with regard to the genes
      included in the interclass regions. A general trend for all gene pools of the
      world was revealed: the ratio between the boundary values of selective classes
      and Fe is constant. On the basis of this, a rapid and simple technique for
      estimating selective values of genes was developed. The positions of more than 80
      immunobiochemical gene markers in the selective structure of six gene pools of
      the world (Europe, Asia, Africa, Australia, America, and northeastern Eurasia)
      are presented. The selective structure of five subregions of northeastern Eurasia
      (Caucasus, Europe, Ural, Siberia, and Central Asia) are characterized as well.

PMID- 9929833
TI  - Pregnancy prevention using emergency contraception: efficacy, attitudes, and
      limitations to use.
AB  - Emergency contraception, also called postcoital contraception, is the use of
      hormonal or mechanical methods to prevent pregnancy after an episode of
      unprotected intercourse. Although a number of methods of emergency contraception
      exist, its use in the United States is not widespread. This report reviews
      studies on the efficacy of hormonal methods of emergency contraception, as well
      as the literature on women's and physicians' knowledge of and attitudes toward
      this method of preventing pregnancy. Articles were selected for this review from
      a MEDLINE search using the term "postcoital contraception." These studies show
      that a variety of hormonal regimens are effective in reducing the chance of
      pregnancy when administered within 72 hours of an episode of unprotected
      intercourse. Failure rates range from 0%-4.66%, depending on the regimen and the
      study, although some controversy exists about how to calculate efficacy. Recent
      studies indicate that mifepristone (RU486) may be more effective than other
      methods, with fewer side effects. However, the more significant issue surrounding
      emergency contraception may be the reasons for its infrequent use in this
      country. A number of limitations to use have been identified in the literature,
      including lack of knowledge of the method among patients and physicians,
      inadequate counseling, and fears that widespread use of emergency contraceptives
      would lead to less consistent use of other methods of contraception.

PMID- 9929834
TI  - Emergency contraception: lack of awareness among patients presenting for
      pregnancy termination.
AB  - STUDY OBJECTIVE: Emergency contraception, otherwise known as postcoital
      contraception, refers to a group of birth control modalities that, when used
      after unprotected intercourse within defined time constraints, can markedly
      reduce the risk of a resultant unintended pregnancy. The English literature,
      using British and American awareness data, consistently claims that these
      contraceptive options are underutilized in the United States because of a lack of
      patient and physician awareness of their existence. The objective of this study
      was to determine the level of awareness of postcoital contraceptive techniques in
      a population of American women who were presenting for pregnancy termination. The
      secondary goal was to calculate (theoretically) how many of these surgical
      terminations could have been prevented through the use of postcoital
      contraception. METHODS: A questionnaire was administered to patients presenting
      to an abortion clinic. It was intended to anonymously identify patient
      demographics and knowledge of the various emergency contraceptive options and, in
      hindsight, to determine what percentage of these women would have been willing
      candidates for one of these medical modalities. On completing the questionnaire,
      all patients received an emergency contraceptive information sheet for future
      consideration. RESULTS: Eighty-three patients completed the study. They ranged in
      age from 15 to 44 years (mean, 24 years). Forty-six percent of the patients were
      21 years of age or younger. A total of 71% of all patients had no real knowledge
      of the existence of emergency contraceptive options; 26% had some limited
      knowledge, and only 3% had somewhat complete and valuable information. Fifty-one
      percent of the patients would have been appropriate, realistic, and willing
      candidates for at least the emergency contraceptive pill. Assuming at least a 75%
      effectiveness rate for the emergency contraceptive pill, 38% of the surgical
      pregnancy terminations performed on this population of women could have been
      avoided. CONCLUSION: Our data confirm that emergency contraceptive options are
      underutilized because of a lack of patient awareness. Contraception education,
      especially directed toward adolescents, should include disseminating enhanced
      information about postcoital contraception options.

PMID- 9929835
TI  - Relationship between perceived parental monitoring and young adolescent girls'
      sexual and substance use behaviors.
AB  - STUDY OBJECTIVE: The purpose of the study was to examine the independent effects
      of perceived parental monitoring on sexual experience, contraceptive, and
      substance use. DESIGN, SETTING, AND PARTICIPANTS: Adolescent females at an urban
      based adolescent clinic (N = 174; 41% sexually experienced) rated the extent to
      which they were directly and indirectly monitored by their parents. MAIN OUTCOME
      MEASURES: These perceptions were compared with reported contraceptive use as well
      as substance use. Direct parental monitoring was best described using two
      dimensions: direct monitoring and direct monitoring when with peers. RESULTS:
      Direct monitoring was found to be associated with the use of hormonal birth
      control methods at last intercourse. Direct parental monitoring when with peers
      was found to be associated with less use of alcohol and cigarettes. CONCLUSIONS:
      These data suggest that parental monitoring is a relevant factor for primary care
      physicians to explore during treatment.

PMID- 9929836
TI  - Combined oral and vaginal treatment of severe vulvovaginitis during childhood.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of combined oral and vaginal
      administration of antibiotics. DESIGN: Treatment and follow-up examination of 54
      cases of severe vulvovaginitis. SETTING: Division of Pediatric and Adolescent'
      Gynecology, Second Department of Obstetrics and Gynecology, University of Athens,
      Greece. PARTICIPANTS: Girls aged 1-10 years seen at the clinic of the above
      listed institution. INTERVENTIONS: Vaginal application of antibiotics. MAIN
      OUTCOME MEASURES: Vaginal culture and vaginoscopy. RESULTS: Treatment achieved
      microbial eradication in 51 of 54 patients (94%). In most patients, relief of
      symptoms was achieved after 2-3 days. No adverse effects were reported.
      CONCLUSIONS: Treatment was highly effective and simple to administer, and no
      complications were observed. A further advantage of this approach is the shorter
      duration of treatment.

PMID- 9929837
TI  - Ovarian surgery in premenarchal girls.
AB  - STUDY OBJECTIVE: This study was undertaken to assess the indications, procedures,
      and pathology in premenarchal girls undergoing ovarian surgery. DESIGN:
      Retrospective chart review. SETTING: University of Michigan Medical Center 1980
      1996. PARTICIPANTS: Premenarchal girls, who underwent ovarian surgery.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: All available charts (n = 52) had
      information extracted concerning age at time of surgery, presenting symptoms,
      preoperative and postoperative diagnosis, procedure, and pathology report.
      RESULTS: Of the 52 patients, 50% were less than 1 year old, 31% were between 1
      and 8 years old, and 19% were between 8 and 12 years old. Presenting complaints
      in 31 patients included structural and or endocrinologic abnormalities, and the
      other 21 patients presented with abdominal or systemic complaints. The most
      common preoperative diagnosis was an abdominal/pelvic mass (n = 24). The
      postoperative diagnoses revealed 18 torsions and 16 ovarian masses without
      torsion, 8 chromosomal abnormalities, 5 hernias, and 5 malignancies. Procedures
      included 37 salpingo-oophorectomies (28 unilateral and 9 bilateral), 7
      oophorectomies, and 7 cystectomies. One patient underwent a staging procedure.
      Pathology reports confirmed hemorrhagic infarctions (n = 19), dysgenic gonads (n
      = 8), simple cysts (n = 7), teratomas (n = 6), theca lutein cysts (n = 4),
      fibroma (n = 1), stromal tumor (n = 1), mucinous cystadenoma (n = 1), granulosa
      cell tumor (n = 1), uterine neuroblastoma (n = 1), mixed germ cell neoplasm (n =
      1), metastatic Wilms' tumor (n = 1), and gonadoblastoma (n = 1). CONCLUSIONS:
      Torsion was the most common diagnosis in our study group and was usually
      unsuspected. Premenarchal ovarian surgery usually included removal of the entire
      ovary. However, because malignancies are uncommon in this population (9.6%), a
      cystectomy should be considered when appropriate and technically feasible.

PMID- 9929838
TI  - Perceived and measured weight changes during adolescent pregnancy.
AB  - STUDY OBJECTIVES: This study examines the accuracy of recalled gestational weight
      gain and maximum weight gain during pregnancy and evaluates which factors have an
      impact on those estimates. DESIGN: Cross-sectional survey. SETTING: Adolescent
      pregnancy clinic in an urban hospital. SUBJECTS: Forty postpartum adolescents
      were recruited. Half the subjects were evaluated within 6 months postpartum, and
      half were seen over the next 9 months. MAIN OUTCOME MEASURES: Months postpartum,
      intrapartum weight gain documented in chart, maximum weight documented in chart,
      recalled intrapartum weight gain, recalled maximum weight; differences between
      chart-documented and recalled weight gain and maximum weight. RESULTS: Self
      documented and documented weight gain and maximum intrapartum weights were highly
      correlated (Pearson r = .99), although those at highest weight tended to
      underestimate their weight gain and maximum weight. CONCLUSIONS: Adolescents are
      able to reliably recall weight gain and maximum weight during pregnancy.

PMID- 9929840
TI  - Pelvic examination of the virginal teenager.

PMID- 9929839
TI  - Two cases of breast lymphoma mimicking juvenile hypertrophy.
AB  - Two cases of mammary lymphosarcoma in adolescents, a secondary localization of a
      systemic process, are described. These cases clinically presented as bilateral
      virginal hypertrophies. One patient died while being treated with chemotherapy;
      the tumoral mass in the other patient had been reduced at the end of treatment.

PMID- 9929841
TI  - Management quandary. Premenarchal valvar lesions.

PMID- 9929842
TI  - Infertility at a young age: one patient's story.

PMID- 9929843
TI  - Joan: 'it itches, it burns': psychoanalytic approach to a case of vulvar burning
      syndrome.
AB  - The case report of Joan, a 20-year-old girl, suffering from vulvar burning
      syndrome (vulvodynia), illustrates how under certain circumstances, the body
      expresses what the mind and words are unable to formulate. The skin and the
      genital sphere are areas rich in symbolic expression because of their close
      connection with relational and emotional life. It is up to the dermatologist and
      the gynecologist to detect the signs of the psychic pain behind the somatic
      complaint. Contrary to other cases of vulvodynia previously reported, Joan had
      never suffered from real sexual or physical abuse, but experienced her emotional
      and sexual life in a painfully conflictual way. Through Joan's psychoanalytic
      work, we attempt to show the benefits of such an approach in the search for a
      better quality of life for these patients. A close collaboration between the
      physician and the psychotherapist is needed to improve the treatment of
      pathologies involved in a chronic pain syndrome, where psychological factors may
      play an important part.

PMID- 9929844
TI  - Relationships between premenstrual complaints and perimenopausal experiences.
AB  - This study evaluates whether a history of menstrually-related problems, termed
      premenstrual complaints (PMCs), is a significant predictive marker for a more
      symptomatic perimenopausal experience. Two hundred and ninety-one randomly
      selected urban women, aged between 45 and 55 years were interviewed yearly for
      three consecutive years to record their individual experiences and changes as
      they progressed through the menopause transition. Repeated measures were obtained
      on a range of physical, psychological and social indicators. The experiences of
      women who reported a self-defined history of premenstrual complaints (n = 104)
      were compared with those women with no prior premenstrual problems (n = 187) and
      predictors of perimenopausal symptoms were assessed. Relationships were found
      between a prior history of both physical and psychological premenstrual
      complaints and a more symptomatic perimenopause characterised by dysphoria,
      skeletal, digestive and respiratory symptoms (all ps < 0.05). The more
      symptomatic women also reported pronounced interpersonal stress (p < 0.001),
      significant 'hassles', current smoking and low exercise (ps < 0.05). The findings
      support predictive relationships between a prior history of premenstrual problems
      and a more problematic menopause transition. The issues of vulnerability and help
      seeking behaviors are discussed.

PMID- 9929845
TI  - How patients with gynecological cancer experience the information process.
AB  - This qualitative study was designed to explore the kind of experiences women with
      a diagnosis of gynecological cancer have with regard to information given during
      their illness and how it could be improved. Data were collected through a
      semistructured interview which focused on the 24 women's experiences of the
      information given. The interviews were tape-recorded and transcribed verbatim for
      each participant, and analysed using a content analysis. Two main themes were
      revealed: to actively address questions, and the right to receive honest
      information. The results also include a short description on how information was
      offered, the patients' opinion of it and how the patients had sought information
      for themselves. When patients address questions they want honest answers. Some
      effort should also be made to identify patients who do not want information. If
      it is in accordance with the patient's and next-of-kin's wishes, efforts should
      be made to provide information at times when both can participate. Information
      given jointly to the patient and her family lessens the burden for the patient.
      In Sweden today, as a result of recent political decisions, caregivers must also
      consider the need to discuss economic issues.

PMID- 9929846
TI  - Incidence and demographic correlates of depressive symptoms during pregnancy in
      an inner London population.
AB  - This paper reviews the literature on antenatal depression and reports on a recent
      survey of depressive symptoms among 407 women attending an inner London antenatal
      clinic. The high level of depressive symptoms in this survey was in line with
      that recently reported from a deprived inner-city population in the United
      States. Depressive symptoms were associated with having no educational
      qualifications, being unmarried, the woman being unemployed, having poor support
      from a partner if present, and being in second or subsequent pregnancy. Doctors
      should be aware that women are not especially protected from symptoms of
      depression during pregnancy. The association with socioeconomic problems suggests
      that this is one aspect of morbidity among disadvantaged people. There is a need
      for more research on the causes of depression during pregnancy and on evaluation
      of medical treatment and social intervention.

PMID- 9929847
TI  - Family planning knowledge, attitudes and practices in women with schizophrenic
      spectrum disorders.
AB  - This study set out to test three hypotheses about family planning in women with
      schizophrenic spectrum disorders, as compared to demographically comparable non
      mentally ill control women: that they (1) report at least as much unprotected
      intercourse while not desiring pregnancy; (2) have less knowledge about
      contraception; and (3) perceive more, and different, obstacles to obtaining or
      using birth control. A semistructured Family Planning Interview was administered
      to subjects (n = 44) with Research Diagnostic Criteria diagnoses of schizophrenia
      and schizoaffective disorder, and to non-mentally ill control subjects (n = 50).
      The participants had high rates of unprotected intercourse, as did non-mentally
      ill controls. They had significantly less reproductive and contraceptive
      knowledge than the control subjects, and were more likely to perceive birth
      control as difficult to obtain. The most common reason women with schizophrenic
      spectrum disorders gave for failing to use birth control was that they did not
      expect to have sex, while that given by non-mentally ill subjects related to side
      effects of birth control. Important obstacles to family planning in women with
      schizophrenic spectrum disorders include relative lack of knowledge and
      difficulty planning ahead. Although many women with schizophrenia could benefit
      from long-acting, reversible contraception, many may be unaware of those options
      and/or may find them difficult to obtain. Integrating family planning with mental
      health care might better address the unique needs of this population.

PMID- 9929849
TI  - Answering Kevorkian's challenge: is this the way we want to die?

PMID- 9929848
TI  - Psychological distress and infertility: forty years of research.
AB  - A critical review is provided of the literature of psychosomatic infertility,
      including research on the relation of psychological distress and infertility,
      interventional studies in which efforts to treat underlying psychopathology are
      related to success or failure in conceiving, and proposed neurophysiological
      mechanisms that relate psychological status and fertility. Directions for future
      research to address the issue of psychological distress and infertility are also
      outlined.

PMID- 9929851
TI  - Patient education. Getting enough sleep.

PMID- 9929852
TI  - Toward optimal health: the experts respond to sleep deprivation. Interview by
      Jodi Godfrey Meisler.

PMID- 9929850
TI  - SERMs: the benefits of estrogen without the risks?

PMID- 9929853
TI  - Fat: can't live with it, can't live without it. Part I.

PMID- 9929854
TI  - Medicine, the media, and bioethics.

PMID- 9929855
TI  - The genetic origins of ovarian failure.
AB  - Premature ovarian failure (POF) is a condition characterized by cessation of
      ovarian function before the age of 40. The recent meeting at the National
      Institute of Child Health and Human Development brought together experts from
      diverse disciplines to share current perspectives on the genetic and physiologic
      origins of POF, with the idea that insights gained from these studies may provide
      important clues about the regulation of normal ovarian aging and perhaps aging
      processes in general. It was suggested that several murine genes, including Zfx,
      c = kit, and the kit ligand, should be fertile candidates for investigation of
      the etiology of POF in human families. The specific roles of the human DIA and
      FMR1 gene products in germ cell development need clarification in murine models,
      and there are more as yet unidentified genes residing on the long arm of the X
      chromosome that are also implicated in the regulation of human ovarian function.
      Genes acting at later stages of oocyte or ovarian follicle function, such as
      gonadotropin hormones and receptors, are responsible for POF in some women. POF
      has been found to be a heterogeneous disorder, the dissection of which offers
      promising insights into mechanisms governing germ cell origination, migration,
      and proliferation, meiotic mechanisms, and factors governing oocyte maturation
      and survival.

PMID- 9929856
TI  - Is there an association between hormone replacement therapy and breast cancer?
AB  - The fear of breast cancer has been suggested as a potential reason why only a
      relatively small percentage of postmenopausal women who would benefit from
      hormone replacement therapy (HRT) are current users. The equivocal results from a
      large number of epidemiologic studies make it difficult to evaluate whether an
      association does indeed exist between the use of HRT and the incidence of breast
      cancer. The inability to provide conclusive evidence for or against this
      relationship may be attributed to methodologic problems in these studies,
      including small sample sizes, lack of information on specific hormonal
      preparations (e.g., dose and type), failure to control for the type of menopause,
      and surveillance bias. In an attempt to generalize results from different studies
      in a systematic manner, several meta-analyses have been conducted of the effects
      of estrogen replacement therapy (ERT) or HRT on the risk of breast cancer. This
      article summarizes the data from these meta-analyses and incorporates data from
      studies published after these meta-analyses that have addressed this question.
      Data from ongoing studies that use a randomized, controlled, longitudinal design
      on large numbers of women are necessary before a possible association between the
      use of HRT and breast cancer can be ascertained.

PMID- 9929857
TI  - The influence of sex hormones on obesity across the female life span.
AB  - Women have a higher prevalence of obesity than men in most developed countries.
      Obesity affects many aspects of women's health by increasing risk for heart
      disease, diabetes, breast cancer, and infertility. One reason for the gender
      difference in obesity may be that fluctuations in reproductive hormone
      concentrations throughout women's lives uniquely predispose them to excess weight
      gain. Studies in experimental animals and women have shown that hormonal changes
      across the menstrual cycle affect calorie and macronutrient intake and alter 24
      hour energy expenditure. Pregnancy is a significant factor in the development of
      obesity for many women. Various factors are associated with excess weight
      retention following pregnancy, including weight gain during pregnancy, ethnicity,
      dietary patterns, and interval between pregnancies. There is a need to tailor
      recommendations for energy intake during pregnancy to individual women, and
      recent evidence also suggests that the timing of weight gain during pregnancy is
      a critical factor. Menopause is also a high-risk time for weight gain in women.
      Although the average woman gains 2-5 pounds during menopausal transition, some
      women are at risk for greater weight gains. There is also a hormonally driven
      shift in body fat distribution from peripheral to abdominal at menopause, which
      may increase health risks in older women. Hormone therapies have varying impacts
      on body weight and fat distribution. In summary, hormonal fluctuations across the
      female life span may explain the increased risk for obesity in women. Awareness
      of these factors allows development of targets for prevention and early
      intervention.

PMID- 9929858
TI  - Body mass index, smoking, and mortality among older American women.
AB  - The relationship among body mass index (BMI, kg/m2), smoking status, and overall
      mortality remains controversial. To assess this relationship in a representative
      sample of older women, we used data from the Panel Study of Income Dynamics
      (PSID). The PSID (begun in 1968) is a prospective longitudinal cohort study
      designed to examine economic and demographic behavior. Respondents were 1355
      women age > or = 50 when they initially completed the Self-Administered Health
      Questionnaire in 1990. Data collected included self-reported height and weight,
      years of completed education, smoking status (never versus ever), and responses
      to four health-related questions (e.g., retired due to ill health, difficulty
      eating). Respondents were followed, including the date of death if respondent
      died, through 1994. Cox proportional hazard regression revealed a U-shaped
      relationship irrespective of whether smoking was included in the model. The base
      of the curve was fairly wide, suggesting that a broad range of BMI is well
      tolerated by older women. The minimum mortality (estimated from fitted
      proportional hazard models) for both the smoking and nonsmoking models occurred
      at a BMI of approximately 34. When interactions between smoking status and BMI
      terms were added to the model, the interactions were not jointly significant (p =
      0.071). Moreover an exploratory plot of the BMI-mortality curve among never
      smokers (n = 800) revealed a curve that moved away from being U-shaped toward
      being more monotonically decreasing. It is concluded that these data suggest that
      there is no evidence that the U-shaped BMI-mortality relationship observed is
      caused by confounding by smoking status.

PMID- 9929859
TI  - Urge incontinence: the patient's perspective.
AB  - Urge incontinence has a profound effect on the day-to-day lives of women. The
      purpose of this study was to identify specific aspects of functioning and well
      being affected by urge incontinence or mixed incontinence with a primary urge
      component. We conducted six focus groups of 65 racially and age diverse,
      community-dwelling women with urge incontinence. Transcripts of the focus groups
      were quantitatively analyzed for word use frequency with QSR NUD*IST software.
      Demographics, symptomatology, and the impact of incontinence on daily activities
      and feelings were assessed by questionnaire. Participants in the focus groups
      were on average 62 years of age; 52% were nonwhite, and 26% had a high school or
      less education. In the three identified broad domains, 52% of domain-related
      words were associated with feelings, 40% with activities, and 8% with
      relationships. Frequently identified references were bathroom availability (24%),
      loss of control (14%), anxiety (11%), and sleep disturbance (10%). Women under
      the age of 70 compared with older women more commonly identified feeling
      unattractive and low self-esteem (12% versus 2%, p < 0.007) and adverse effects
      on dating and sexual activity (45% versus 0%, p < 0.02). The effect of
      incontinence on quality of life correlated with frequency, nocturia, and pad use
      (Kendall's tau beta 0.02-0.32, p < 0.05). Urge incontinence affects many quality
      of life issues and contributes to limitation of activities, loss of control, and
      negative self-perception. Focus groups of diverse women with urge incontinence
      symptomatology are useful in understanding these effects.

PMID- 9929861
TI  - Milk leakage in nonlactating women: a randomized clinical trial evaluating a
      polyvinyl chloride device versus disposable breast pads.
AB  - A randomized clinical trial was carried out to evaluate the safety and
      helpfulness of the LactaPrev System (LPS) compared with disposable pads for milk
      leakage management for postpartum, nonlactating women (those who do not
      breastfeed). Fifty-five women completed the single-blind, randomized trial.
      Participants wore each device on each breast concurrently. Assignment of the LPS
      or pad to each breast was done randomly. Fifty-eight percent of participants
      preferred the LPS. The longer the participation in the study, which correlated
      with the duration of milk leakage, the greater the preference (p = 0.05).
      Preference was related to bra size (p = 0.05). The smaller the bra size, the
      greater the preference for the LPS. There was no greater incidence of
      complications from the LPS compared with the disposable breast pad.

PMID- 9929860
TI  - Prospective association of smoking and alcohol use with cognitive function in an
      elderly cohort.
AB  - Cross-sectional studies of the associations of alcohol and tobacco use with
      cognitive function do not take into account behavior change after memory loss or
      differential survival. This prospective study examines the association of
      cigarette smoking and alcohol consumption at baseline with risk of poor cognitive
      function 13-18 years later. Between 1973 and 1975, 1469 relatively well-educated,
      noninstitutionalized men and women from Rancho Bernardo, California, answered
      standardized questions about smoking and alcohol consumption. Between 1988 and
      1991, 511 of these men and women completed five standardized cognitive function
      tests. At baseline, 20.4% of the men and 23.0% of the women were cigarette
      smokers. Smoking was associated with increased mortality in men but not in women.
      In surviving male participants, cognitive function test scores did not
      significantly differ by baseline smoking status. Among female participants,
      smoking was associated with categorically defined poorer function on two of five
      tests. At baseline, 16% of the men and 29% of the women were nondrinkers.
      Drinking more than two drinks per day was associated with decreased mortality in
      both sexes. Among women, increasing consumption of alcohol predicted a
      significant decline in the long-term recall and savings scores of the visual
      reproduction test. Moderate drinking, approximately two drinks per day, predicted
      categorically defined poor performance on the Buschke long-term recall task in
      women. Alcohol consumption was not associated with cognitive function in men.
      Overall, the observed associations were weak, and no clear pattern was observed.
      Although there were some gender differences in observed associations and a
      survivor effect cannot be excluded, data from these healthy, educated,
      noninstitutionalized people offer no compelling evidence that social drinking or
      cigarette smoking causes or prevents impaired cognitive function in old age. The
      large number of comparisons and inconsistent results suggest that the few
      statistically significant findings may be spurious. Additional long-term
      prospective studies are needed to determine the generalizability of these
      findings to individuals in less healthy or less well-educated cohorts.

PMID- 9929863
TI  - More websites for women's health.

PMID- 9929862
TI  - Personal health among midlife women hospital employees.
AB  - We hypothesized that women employees working in a hospital environment would be
      particularly attuned to aspects of personal health, well-being, and disease
      prevention. We performed an observational study at a local hospital, offering
      free assessments in its outpatient women's wellness screening program to women
      employees aged 39-60 years. Data from the first 60 women to enroll in the program
      are presented as a test of our hypothesis. Undiagnosed hypertension, abnormal
      lipid profiles, glucose intolerance, alcohol abuse, abnormal cervical cytology,
      breast masses, depression, or combinations of these were found in 49 of the 60
      women. Twenty-one women were obese. Most women with abnormal findings did not
      follow specific personalized recommendations for remedial follow-up, including
      referral to a specialist. An important percentage of midlife women employees at
      this hospital exhibited unhealthful personal behaviors, had unrecognized disease,
      and did not use recommended health screening practices. The data emphasize the
      benefit for employees who participate in medical facility worksite health
      promotion programs.

PMID- 9929864
TI  - Women's Health LiteratureWatch.

PMID- 9929865
TI  - [Meeting of the Saxon Ophthalmologic Society 27-29 November 1998, Oberwiesenthal:
      "Traumatology of the Eye, Observations"].

PMID- 9929866
TI  - [St. Nicholas-day meeting of the Berlin-Brandenburg Society of Ophthalmology.
      Berlin, 5-6 December 1998].

PMID- 9929867
TI  - [Some aspects of the pathogenesis of HIV infection].

PMID- 9929868
TI  - [Molecular biological aspects of carcinogenesis associated with the Epstein-Barr
      virus].

PMID- 9929869
TI  - [New classes of ribozymes isolated by in vitro selection. RNA ligases].

PMID- 9929870
TI  - [Variability of neurotrophin receptor structures].

PMID- 9929871
TI  - [Polymorphism of HLA-DQA1 and DQB1 genes in the Moscow population and in patients
      with diabetes mellitus types 1 and 2].

PMID- 9929872
TI  - [cis-Elements in the 5'-region of the Oct-1 gene. Possibilities of
      autoregulation].

PMID- 9929873
TI  - [Preferred transcription of the copia retrotransposon in Drosophila melanogaster
      testes].

PMID- 9929874
TI  - [Simple and complex microsatellite DNAs in the region of the Drosophila vinculin
      gene].

PMID- 9929875
TI  - [Characteristics of new family of tandemly organized repeats STR47 in common
      voles].

PMID- 9929877
TI  - [Characteristics of Trypanosoma scelopori kinetoplast DNA: conserved region of
      the minicircle as a molecular-taxonomic feature].

PMID- 9929876
TI  - [Disruption of polytenization of DNA from the euchromatin region of the
      Drosophila melanogaster X-chromosome, caused by euheterochromatin restructuring].

PMID- 9929878
TI  - [Amber-suppressive tRNA from bacteriophage T5: construction of genes and
      determination of the effectiveness of suppression in vivo].

PMID- 9929879
TI  - [Noncanonical conformation of nucleic acids: structure with slipped-loops,
      occurring in DNA oligonucleotides].

PMID- 9929880
TI  - [Analysis of distribution of alternating-sign charged clusters on the surface of
      globular proteins].

PMID- 9929881
TI  - [Interaction of endonuclease EcoRI with short specific and nonspecific
      oligonucleotides].

PMID- 9929882
TI  - [E1A-induced apoptosis in rat embryonal fibroblasts is not suppressed by
      introducing the c-Ha-ras oncogene].

PMID- 9929884
TI  - [Stability of chromatin in a cell-free system of Drosophila embryos].

PMID- 9929883
TI  - [Functional properties of hepatic T-lymphocytes from mice immunized with an
      alloantigen in vivo].

PMID- 9929885
TI  - [Topological characteristics of chromatin in a cell-free system from Drosophila
      embryos].

PMID- 9929887
TI  - [A functional model of the central epitope of the V3 loop of HIV-1 gp120 when
      complexed with antibodies].

PMID- 9929886
TI  - [Nuclear matrix proteins, specifically binding a murine satellite].

PMID- 9929888
TI  - [Tandem bifunctional derivatives of short oligonucleotides--inhibitors of
      replication of the human immunodeficiency virus in cell culture].

PMID- 9929889
TI  - [Amino acid sequences of proteins, coded by the 3'-ends of regions of genomes of
      two morphological classes of shallot virus X virions].

PMID- 9929890
TI  - [Modern directions in studying biologically active substances from basidial
      fungi].
AB  - Nonconventional uses of basidial fungi as producers of valuable biologically
      active compounds are reviewed. Basidiomycetes are now most extensively used in
      the medical industry to obtain antibiotics, enzymes, lipids, and various drugs
      acting on the immune system (hypocholesterolemic, antiviral, hypotensive,
      hypoglycemic, etc.). Recent data on toxic and psychotropic substances of
      Basidiomycetes and of their aromatic compounds responsible for the so-called
      fungal flavor are also considered. Finally, the increasing significance of
      Basidiomycetes for human practice is underlined.

PMID- 9929891
TI  - [Absorption of nitric oxide by a strain of Bacillus stearothermophilus and its
      use in a bioreactor for purifying air].
AB  - A new Bacillus stearothermophilus strain, INMI 50, was isolated and identified.
      Cells of this strain immobilized on a ceramic carrier demonstrated a high NO
      uptake in a bioreactor. The bioreactor volume was 4 l; air flow, 100 l/h; initial
      NO concentration, 5 ppm; and temperature, 60 degrees C. Glycerol or 1,2
      propanediol was used as carbon and energy source. The uptake of NO was 60-90% of
      the initial concentration over six months of continuous operation of the
      bioreactor. The developed procedure can be used for removal of nitrogen oxide
      from products of combustion of diesel fuel or from air in production areas.

PMID- 9929892
TI  - [Purification of phospholipase A2 from bee venom on silochrome CX- 3B].
AB  - A new and simple procedure is proposed for the purification of phospholipase A2
      from Bee Venom, which includes three stages of chromatography on silochrom CX-3B.
      We offer original method of desalting and concentration of the enzyme used
      chromatography on silochrom CX-3B. The activity of enzyme is approx. 1200 U/mg
      lyophilizate (approx. 1400 U/mg protein).

PMID- 9929893
TI  - [A system of coupled reactions for enzymatic synthesis of L-malate].
AB  - A simple and inexpensive process of synthesis of L-malic acid from lactic acid in
      a system of coupled reactions is described. The resulting L-malic acid was
      isolated from the reaction mixture by ion-exchange chromatography. This synthesis
      is promising for the full-scale production of high-purity malic acid.

PMID- 9929894
TI  - [Conversion of beta-carotene and some beta-apocarotinoids under the effect of
      substances from the intestinal mucosa].
AB  - Products of cleavage of beta-carotene and certain apocarotenoids (beta-apo-4',
      8', 10', and 12'-carotenols and citranaxanthol) were studied, and the dynamics of
      their generation in the presence of an enzyme preparation isolated from rabbit
      intestinal mucosa was determined. The data suggest that metabolism of beta
      apocarotenols involves the production of retinal and beta-apo-14'-carotenal
      mediated by enzymes different from beta-carotene-15,15'-dioxygenase, which
      converts beta-carotene to retinal. A scheme of metabolic conversion of beta
      carotene is discussed.

PMID- 9929896
TI  - [Animal nutrition in veterinary science].
AB  - In the past, emphasis was on deficiencies in relation to nutrition and animal
      health, but nowadays it is more on the relevance of nutrition (or nutrients) to
      the aetiology and prevention of disease. This is illustrated by an outline of the
      association between the (over)feeding of dairy cattle before and around calving
      and the incidence of diseases that frequently occur post calving. The nutritional
      management of clinical diseases and the application of enteral or tube feeding is
      nowadays part of modern pet animal practice. The difference between a nutrient
      and a medicine is becoming vague and the application of recombinant DNA-technics
      offers new and interesting possibilities to increase the medicinal value of
      certain feeds. These trends in animal health care together with the wish of
      clients to be informed of the feeding of their animals, either pet animal of farm
      animal, greatly increase the demand for knowledge and skill of animal nutrition.
      The current veterinary medicine curriculum does not allow sufficient time for
      students to gain the necessary knowledge and skill in animal nutrition. Therefore
      specialists in veterinary nutrition are needed who can advice the providers of
      veterinary nutritional and other health care services in order to use optimal the
      nutritional support possibilities in animal health care as well as in improving
      productivity.

PMID- 9929895
TI  - [Isolation of heparin and chondroitin sulfate from animal tissue by an ion
      exchange method].
AB  - Isolation of mucopolysaccharides (heparin and chondroitin sulfate), from animal
      tissue by ion exchange was studied. The yields of heparin and chondroitin sulfate
      of up to 20,000-150,000 units/kg and 14 g/kg, respectively, can be obtained
      depending of the type of the raw material used and the sorbent, which absorbs
      heparin and chondroitin sulfate from aqueous solutions in amounts of 100-250 mg
      per g sorbent. Ion-exchange sorption of mucopolysaccharides on synthetic sorbents
      permits extracting fractions of these compounds with the maximum biological
      activity.

PMID- 9929897
TI  - [Nutrition-related problems in pet birds].
AB  - The detection and correction of dietary errors plays an important role in avian
      medicine. Examples of diseases caused in part by a deficiency or abundance of a
      nutrient include hypovitaminosis A in birds of the parrot (Psittacidae) family,
      hypocalcemia in the African grey parrot, goitre in budgerigars, and iron storage
      diseases in the minah and toucan. Hypovitaminosis A can lead to metaplasia of
      mucous membranes, which in turn can lead to chronic rhinitis and respiratory
      fungal infections. Vitamin A deficiency is caused by feeding a seed based diet.
      Seed mixtures are often deficient in calcium, and nutritional secondary
      hyperparathyroidism can develop if an additional source of calcium, in the form
      of ground shells, is not provided. Tetanic symptoms as a result of hypocalcemia
      are only seen in the African grey parrot and the timneh parrot. Over
      supplementation of vitamin D gives rise to poisoning with polyuria and polydipsia
      as common initial symptoms. The exact cause of iron storage diseases in toucans
      and minahs is not known. A diet low in iron and vitamin C is advised as therapy.
      Goitre can develop in budgerigars as a result of iodine-deficient drinking water
      and provision of a seed mixture based on millet. An unbalanced or multideficient
      diet can give rise to reproductive disorders, abnormal feathers, or infections as
      a result of diminished resistance. It is usually not possible to relate the cause
      of these diseases in a simple way to the composition of the diet. Obesity, which
      occurs in the galah, Amazon parrot, and budgerigars, can lead to fatty liver and
      lipoma. A gradual reduction in weight, by means of calorie restriction, is
      recommended. Commercially available nutritionally balanced bird food is often
      effective.

PMID- 9929898
TI  - [Nutrition of young piglets in relation to weaning problems].
AB  - Weaning at the age of 3-4 weeks has great consequences for piglets. The
      consequences of the change from milk to solid food are discussed with regard to
      the supply of nutrients, the available enzyme capacity of the digestive tract,
      and the morphological and functional changes in the gut. A number of preventive
      measures are discussed, with a distinction being made between general measures,
      measures related to the composition of the diet, and measures related to specific
      additives. Future research should clarify the mechanism of action of specific
      additives and pay more attention to the uptake of nutrients in piglets in the
      period just after weaning.

PMID- 9929899
TI  - [Metabolic insights and nutrition of poultry].
AB  - Excessive specialization and high production requirements place high demands on
      the metabolism of poultry. A number of metabolic problems, such as disturbances
      of energy metabolism (affecting mainly hens) and mineral balance (affecting
      mainly laying hens), affect performance. Nearly all these problems are
      multifactorial in nature, but diet, and in particular the interaction between
      diet and phenotype, plays an important role. The problem of ascites in broiler
      hens is discussed in relation to external and genetic causative factors. Genetic
      factors can be further subdivided into structural and functional causative
      factors. This distinction has important consequences. For example, sudden death
      syndrome can be distinguished as a separate entity. Fatty liver syndrome in
      laying hens, and gout and urolithiasis in chicks and hens are briefly discussed.
      Finally, some of the most important or most common skeletal problems affecting
      poultry, namely, tibial dyschondroplasia, battery fatigue, rickets, and
      chondrodystrophy, are briefly discussed in the context of the dietary factors
      that underlie these disorders or which can be used as treatment.

PMID- 9929900
TI  - [PRRS: the current situation].

PMID- 9929901
TI  - [The noncoherent components of evoked brain activity].
AB  - Poststimulus spectral EEG changes and their correlation with evoked potential
      (EP) were analyzed. The non-stationary components of the brain evoked activity
      were revealed in 32 volunteers during simple motor reaction and choice reaction
      to visual stimuli. This nonstationary activity was manifested in poststimulus
      changes in the mean wave half-period duration (MWHPD) and mean wave half-period
      power of the delta- and beta-frequency oscillations computed in the EEG
      realizations after the EP subtraction. The latencies of high-frequency EP
      components fell into the intervals of the MWHPD decrease and increase in the
      power of beta-oscillations, and the latencies of low-frequency EP components
      coincided with the intervals of the MWHPD increase and decrease in the power of
      delta and beta-oscillations, which pointed to correlation of these changes with
      the EP.

PMID- 9929902
TI  - [The stabilization of cortical evoked potentials during selective visual
      attention].
AB  - The event-related potentials (ERP) to lateralized moving visual stimuli
      (administered to the right and to the left of the subject) were recorded in six
      derivations in eight healthy subjects during passive viewing and selective
      attention to one of the stimuli (the relevant one), which demanded precise and
      rapid motor reaction. It was shown that during the selective voluntary attention
      correlation between successive ERP was substantially higher than that under
      conditions of passive (involuntary) attention, i.e. the ERP in the occipital,
      parietal, and frontal derivations during voluntary attention were more stable.
      The less was correlation between the ERP at passive viewing, the greater was the
      difference between the values of correlation coefficients during selective and
      passive attention. It is suggested that role of selected attention consists in
      stabilization of activity of the cortical structures, which are involved in
      solving the behavioral task.

PMID- 9929903
TI  - [The individual profile characteristics of cerebral interhemispheric asymmetry
      during visual stimulation in healthy subjects and in patients with the spastic
      form of infantile cerebral palsy].
AB  - Individual profiles of brain interhemispheric asymmetry (IPA) and stability in
      maintenance of the vertical posture have been studied in healthy children and
      adults and patients with the spastic form of the infantile cerebral palsy before
      and after visual stimulation. The IPA were built on the basis of motor asymmetry
      of hands, asymmetry of visual half-fields, and asymmetry of muscle extension tone
      in vertical position in Romberg test at computer stabilograph. The visual
      stimulation was realized by unilateral tachistoscopic administration of a verbal
      stimulus in the visual half-field on the side of worst detection of the master
      stimulus during the procedure of initial IPA construction. The IPA were different
      in children, adults, and patients. Even single visual stimulation changed the
      initial IPA (not only its visual but motor and stability-related components). A
      correlation was shown between the individual features of realization of the
      vertical position, initial IPA, age of the subjects, and presence/absence of the
      cerebral palsy. The visual stimulation led to a decrease in initially low
      stability and, on the contrary, an increase in initially high stability both in
      healthy subjects and patients with cerebral palsy, regardless of their
      handedness. Increase in stability of the vertical posture was accompanied by a
      decrease in the role of the visual analyzer, and, on the contrary, decrease in
      stability was associated with an increase in the role of the visual analyzer in
      stability control. It is necessary to take into account the dissimilar action of
      sensory stimulation on the IPA and stability of the vertical posture in
      assessment of the effects of sensory stimulation on healthy persons and patients
      with CNS lesions, in particular, with cerebral palsy, in the course of
      development of new ways of treatment.

PMID- 9929904
TI  - [The theta rhythm of the infant EEG and the development of the mechanisms of
      voluntary control of attention in the 2nd half of the first year of life].
AB  - The neurophysiological basis of attention control was studied in infants at the
      second half-year of life, i.e. in the period when the capability for voluntary
      control over behavior fundamentally improves. EEG was recorded in 60 infants aed
      8-11 months in three experimental conditions: 1) attention to an object in the
      visual field (externally controlled attention, or the baseline state), 2)
      anticipation of a person in the peek-a-boo game (internally controlled
      attention), 3) attention to the reappeared person in the peek-a-boo game (control
      condition). The spectral analysis of the EEG data revealed a sharp increase in
      the EEG theta (3.6-6.0 Hz) during internally controlled attention as compared to
      the baseline and control conditions. The theta1 (3.6-4.8 Hz) increase was maximal
      in the frontal derivations. The reactivity of the frontal theta1 during
      internally controlled attention discriminated infants with different abilities to
      maintain this type of attention. The reactivity of the theta2 (5.2-6.0 Hz) was
      maximal in the right temporal derivation (T6) and did not depend on stability of
      the anticipatory attention. The findings point to different functional
      significance of the theta1 and theta2 rhythms in infants. It is suggested that
      synchronization of the frontal theta1 rhythm in infants reflects the activity of
      the anterior attention system which realizes the executive attention control. The
      ability to maintain anticipatory attention increased with age, whereas the
      frontal theta1 synchronization decreased and totally disappeared at the age of 11
      months. At the age of 8 months there was a positive correlation between the
      frontal theta1 synchronization and behavioral index of stability of the
      internally controlled attention. On the contrary, this correlation was negative
      at the age of 9 and 10 months. It is suggested that the age-dependent dynamics of
      the relationship between the frontal theta1 reactivity and attention reflects a
      leap in maturation of the anterior attention system resulting in its more
      economic and efficient functioning.

PMID- 9929905
TI  - [The discrimination of color images in human operative memory].
AB  - Qualitative changes of color image maintained in the operative memory were
      studied using the modified Sperling's strategy. On the basis of estimations of
      difference between any two color images (from nine possible), contained in the
      same memory volume within 50 and 100 ms, the respective mnemonic spaces were
      built and afterwards correlated with the perceptual and semantic spaces. It was
      found out that the maintenance of a color image in the operative memory was
      affected by two simultaneous but independent factors. The first factor described
      the fading, i.e., extent of the intensity loss of the primary color image in the
      process of its maintenance in the operative memory. Fading was accompanied by a
      decrease in the signal-to-noise ratio and increase in the incidence of the casual
      mistakes in comparing the images with each other. The second factor determined
      the systematic transformation of color images in the memory expressed in the
      effect of clusterization of point stimuli and specific change in the between
      point distances (estimations of difference).

PMID- 9929907
TI  - [The structural traits of the signals of aggressive-defensive behaviors in the
      domestic cat (Felis catus L.)].
AB  - The results of the ethological-bioacoustic study carried out in 18 male domestic
      cats are presented in this work. Facial gesture, postural, and acoustic activity
      was recorded. The dynamics of frequency characteristics of sound calls was
      studied by means of parametric analysis, the functional significance of the
      recorded vocalizations was determined in the process of development of conflict
      situations. The results obtained indicate the relationship between the emotional
      state and the dynamics of the spectral characteristics of the sound calls. It was
      shown that the absolute value of the first dominant frequency and signal duration
      reflect the excitation level of mates. A conclusion was drawn that the
      redistribution of power from the first to the second spectral peak is an
      informative sign reflecting the motivation change in the dominant male (from
      threat to attack).

PMID- 9929906
TI  - [The effect of hormones from the peripheral endocrine glands on behavioral,
      learning and memory processes].
AB  - The present study was designed to explore the comparative influence of thyroid,
      adrenal, and gonadal hormones on the capability for learning, retention of memory
      traces and behavior in male rats under conditions of systemic administration of
      synthetic hormonal preparations. Behavior of animals was assessed during the
      active and passive avoidance learning, as well as in the open-field test. It was
      established that the increase in the level of corticosteroid, thyroid, or gonadal
      hormones did not affect the formation and retention of passive avoidance
      learning. Excess of corticosteroids increased behavioral activity but impaired
      the active avoidance learning and the following reproduction of the acquired
      reaction. Excess of gonadal hormones dramatically impaired the performance in the
      conditioned active avoidance test, and excess of thyroid hormones improved the
      active avoidance learning.

PMID- 9929908
TI  - [The effect of anosmia on sex dimorphism in the patterns of orienting
      exploratory, emotional and passive defensive behaviors in rats].
AB  - Sex dimorphic patterns of exploratory behavior in the open-field, passive
      defensive behavior and emotionality were studied in anosmic rats. It was show
      that the long-time anosmia increased the level of exploratory and locomotor
      activities in male rats and changed their behavior in stress situations from
      passive to active form. Anosmia didn't change characteristics of these forms of
      behavior in female rats.

PMID- 9929909
TI  - [The electrical characteristics of the command and motor neurons during the
      acquisition of a conditioned defensive reflex and the development of long-term
      sensitization in snails].
AB  - The mechanisms of conditioning of the defensive pneumostome closure reflex and
      long-term sensitization were studied at the level of electrical characteristics
      of the command and motor neurons. A significant decrease in membrane and
      threshold potentials in the command neurons was observed after the acquisition of
      the defensive reflex and long-term sensitization. These potentials decreased to a
      greater extent in the snails subjected to conditioning after the sensitization.
      Changes in the critical depolarization level for the action potential generation
      and its amplitude were insignificant. Thus, the observed phenomena testify to an
      increase in membrane excitability of the command neurons. Similar changes were
      not found in the motor neurons.

PMID- 9929910
TI  - [The effect of anxiolytics and an anxiogen on the electrical activity of the
      frontal cortex and limbic structures of dogs with different nervous system
      properties].
AB  - The influence of benzodiazepine anxiolytics (diazepam, medazepam, nozepam) and
      anxiogen corasole on the electrical activity of the dorsal hippocampus, frontal
      cortex, basolateral amygdala, and lateral hypothalamus was studied in 8 dogs with
      implanted electrodes. The anxiolytics decreased anxiety and reduced the theta
      rhythm frequency in all the structures under study. The effect was most
      pronounced in the dorsal hippocampus. The excitable dogs with initially more
      frequent theta rhythm turned to be less sensitive to diazepam than more calm
      animals with prevailing inhibition. The higher dose of diazepam was necessary for
      excitable dogs to obtain the same electrophysiological effect. At the end of the
      drug action, the theta-rhythm power significantly increased in the dorsal
      hippocampus in all the animals, and in the excitable dogs it increased also in
      the frontal cortex. Moreover, diazepam produced as decrease in the beta 2
      frequency and increase in the frequency of the alpha-like rhythm. The anxiogen
      intake resulted in an increase in dogs' alertness and motor activity, accompanied
      by an increase in the theta-rhythm frequency. Anxiogen increased the frequency
      asymmetry of theta between hemispheres in the hippocampus and amygdala.

PMID- 9929911
TI  - [The tangential segregation of simple and complex cells in the visual cortex and
      their connections. The universal neocortex modulus].
AB  - Guinea-pig studies testify that in rodents (like in higher mammals) the primary
      afferents from the thalamus and inferior cortical afferents converge on discrete
      columns about 200 mcm in size with zones of secondary convergence between them.
      The cortical columns seem to be primary basic and universal cortical modules,
      since they have similar dimensions and uniform organization in different mammals.
      The columns concentrate simple cells (with complex ones among them) and afferent
      inhibitory neurons; these models are involved in the first stage of cortical
      integration. Local connections of the primary modules differ from those of the
      secondary intermediary zones, which are poor narrow in rodents. The intermediary
      zones progressively develop in phylogeny, and in higher mammals they excel the
      primary modules in dimensions.

PMID- 9929912
TI  - [The activation of the transcription factors of the CRE and AP-1 families
      correlates with the development of plasticity in Helix].
AB  - By means of gel retardation assay the DNA-binding activity of transcription
      factors of CRE and AP-1 families was determined in adult and juvenile (incapable
      for conditioning) Helix snails. The presence of DNA-binding factors of the CRE
      and AP-1 families was shown in adult snails. The active factors only of the CRE
      family were present in juveniles. Activity of these factors increased during
      incubation with serotonin (10(-4) M) and forscolin (5 x 10(-5) M). Both serotonin
      and forscolin modulate learning in adult snails. Absence of activity of AP-1
      family transcription factors (the products of early fos and jun genes in juvenile
      snails belong to AP-1 family) may underlie the incapability for sensitization and
      avoidance conditioning in juvenile snails.

PMID- 9929913
TI  - [The characteristics of the effect of tuftsin on the behavior and on the level of
      biogenic amines in the brain of rats with differing resistance to acoustic
      stress].
AB  - The influence of tetrapeptide tuftsin (Tyr-Lys-Pro-Arg) on learning, exploratory
      activity, emotional behavior, and hypothalamic monoamine content was studied in
      Wistar rats with different resistance to stress induced by acoustic stimuli.
      Positive effects of taftsin were more pronounced in low-resistant rats.
      Administration of taftsin induced in these animals a significant increase in
      reactivity to stimuli of different modalities, the open-field exploratory
      activity, rate of alimentary conditioning and its modification in emotionally
      negative situation. Biochemical examinations showed that in rats with high
      resistance to stress taftsin administration led to a decrease in hypothalamic
      noradrenaline level and increase in dopamine and serotonin levels. On the
      contrary, in low-resistant animals taftsin increased the level of noradrenaline
      and decreased that of dopamine, serotonin, and 5-hydroxyindoleacetic acid. It is
      suggested that different behavioral effects of taftsin in stress-resistant and
      nonresistant rats are caused by its different influence on hypothalamic biogenic
      amines.

PMID- 9929914
TI  - [Biogenic amines in the brain nuclei of August and Wistar rats under repeated
      stress].
AB  - The level of biogenic amines and their metabolites were measured in the brain
      regions involved in the major mechanisms of maintaining sympathetic and
      parasympathetic tones during emotional stress (48-h intermittent immobilization).
      An increase in 3,4-dihydroxyphenylalanine content and a trend to serotonin
      decrease were found in the locus coeruleus of Wistar rats, while in August rats
      an increase in noradrenaline, 3,4-dihydroxyphenylalanine, and 3,4
      dihydroxyphenylacetic acid contents was observed in the same structure. In Wistar
      rats, a decrease in dopamine level was observed in the midbrain reticular
      formation and paraventricular hypothalamic nucleus against the background of the
      increased level of 3,4-dihydroxyphenylalanine in the ventral tegmental area. In
      August rats, an increase in 5-hydroxyindoleacetic acid was revealed in the dorsal
      nucleus of n. vagus, A1 and ventral tegmental areas, and nucleus tractus
      solitarii. The findings suggest that the level of biogenic amine metabolism in
      the structures of the central nervous system during emotional stress is
      determined genotypically.

PMID- 9929915
TI  - [The characteristics of the development of learned helplessness in rats selected
      for the excitability threshold of their nervous systems].
AB  - Exposure of rats selected either by low or high excitability thresholds of the
      nervous system to inescapable foot shocks revealed the different behavior of the
      strains under the action of this type of stress: only the highly excitable rats
      (with low threshold) demonstrated difficulty in adaptive behavior ("learned
      helplessness"). The obtained evidence suggests that the sensitivity to
      inescapable shock may depend on the functional state of the nervous system.

PMID- 9929916
TI  - [The effect of destruction of the hippocampus and removal of the epiphysis on the
      circadian dynamics of mobility in stressed rats].
AB  - Acute swimming stress destroyed the circadian rhythm of motility in rats.
      Bilateral electrolytic lesion of the dorsal hippocampus increased the night
      activity and resistance of animals to stress. Pinealectomy did not affect the
      circadian locomotion but increased rats' sensitivity to dysrhythmic stress
      effect.

PMID- 9929917
TI  - [Communicative behavioral effects and disorders of immunity].
AB  - Rats and mice subjected to stress and/or irradiation or their urine induce
      impairment or the indices of immunologic reactivity in caged together their
      intact mates. It is suggested that communicative behavior, including olfactory
      odor components, affect the state of blood and immunity systems.

PMID- 9929918
TI  - [The behavior of mice from 6 genotypes in 2 tests for anxiety].
AB  - Mice from six inbred strains (CBA, ICR, SWR, BALB/c, DBA/2, and C57BL/6J) were
      tested for anxiety in elevated plus-maze and light-dark box. In the elevated plus
      maze CBA, ICR, and SWR mice spent more time in the open area (open arms and the
      center of the maze) than BALB/c and, especially, DBA/2 and C57BL/6J mice. A
      significant negative correlation was revealed between the percent of time spent
      in the open area and the number of peepings from the enclosed arms. There was no
      correlation between the percent of the open-area time and the number of entries
      into the open arms. A positive correlation was found between the percent of the
      open-area time in the plus-maze test and percent of time spent in the white
      section of the light-dark box. Mice of SWR strain spent 64 percent of the
      experimental time in the white section, whereas C57BL/6J mice spent in the
      illuminated section of the box only 15 percent of time. A significant interaction
      was found between the main index of anxiety (percent of the open-area time in the
      box) and indices of exploratory activity (number of crossed squares and number of
      rearings) in the light-dark test.

PMID- 9929919
TI  - [The participation of the brain dopamine D1 and D2 receptors in the process of
      the development of depression induced by social confrontations in mice].
AB  - Brain D1 and D2 receptors were studied in male mice with repeated experience of
      social defeats in daily intermale aggressive confrontations inducing development
      of experimental depression. Groups of animals were studied after 10 (T10 losers)
      and 20 (T20 losers) days of agonistic confrontations. Mice after 5 days of
      individual housing were used as a control group. In the experimental groups D1/D2
      antagonist cisfluphentixol (0.2 mg/kg) did not affect the communicative behavior
      in the partition test that estimated behavioral reactivity of a male to another
      one. Selective D2 antagonist sulpiride (20 mg/kg), however, decreased these
      reactions in the control group and, in particular, in T10 losers but was
      ineffective in T20 losers. Both antagonists changed behavior in Porsolt's test of
      the control mice and, to a greater extent, of T10 losers but failed to change it
      in T20 losers. Decrease in Bmax in nucleus accumbens and increase in Kd in
      amygdala were revealed in T20 losers with [3H]-SCH 23390 binding assay. The
      obtained evidence shows that development of DISC is accompanied by D1 and D2
      receptor sensitivity changes. Analysis of data suggests the specific
      participation of D1 receptors of the mesolimbic dopaminergic system at the stage
      of developed DISC.

PMID- 9929920
TI  - [The participation of the cholinergic system of the shell and core portions of
      the nucleus accumbens in regulating instrumental behavior in dogs].
AB  - Different effects of carbacholine microinjections in the core and shell parts of
      the n. accumbens were revealed in chronic experiments carried out in 6 dogs. Both
      kinds of microinjections led to unspecific and prolonged motor activation of the
      instrumental defensive reaction.

PMID- 9929921
TI  - [The effect of a preparation from the horns of the saiga antelope on the goal
      directed drinking behavior of rats].
AB  - Saitarin (an extract from the horns of antelope Saiga) depresses complex
      instrumental drinking behavior of rats and induced specific changes in the
      structure of goal-directed behavioral acts. Such changes are to a certain extent
      suppressed by naloxone. The obtained evidence suggest that the effects of
      saitarin are caused by its predominant influence on the processes of
      reinforcement in the course of realization by animals of the learned behavioral
      acts.

PMID- 9929922
TI  - [The effect of antibodies to the serotonin-modulating protein SMP-69 on passive
      avoidance behavior in rats].
AB  - Previously we purified from rat brain the novel protein SMP-69 modulated by
      serotonin. Intracerebral injections of the antibodies to this protein produced an
      increase in exploratory activity of rats in the open-field test. In the present
      work we studied the influence of intracerebral injections of SMP-69 protein
      polyclonal antibodies on passive avoidance behavior of rats. Injections of
      antibodies 24 h prior to learning led to an increase in rats' stay in the dark
      compartment and decrease in time spent in the illuminated compartment in
      comparison to the control animals (injected with rabbit non-immune serum) during
      retest sessions conducted 48 h after learning. No significant difference was
      observed between the control and experimental rats in the retest sessions
      conducted 24 h after learning. Injections of antibodies 48 h after learning did
      not change the behavior of the experimental rats in retest sessions, conducted 24
      h after the injections. The results suggest that the antibodies to SMP-69 affect
      the memory consolidation but do not influence the storage and retrieval.

PMID- 9929923
TI  - [Haloperidol induces changes in the electrocorticogram of rats with genetic petit
      mal epilepsy].
AB  - The WAG/Rij rats, a genetic animal model of human absence epilepsy, were injected
      with D2 autoreceptor antagonist haloperidol. Increase in the amount of spike-wave
      discharges and the prevalence of short spike-wave discharges was observed. The
      pattern of spike-wave discharge sequence changed in a characteristic way. The
      findings may testify to participation of dopaminergic system both in the
      processes of generation and cessation of the spike-wave complex absence epilepsy.

PMID- 9929924
TI  - [An expert system based on the principle of brain functional asymmetry].
AB  - The generalized concept is proposed for automation of secondary data processing.
      Initial information is stored in the knowledge base. During processing the verbal
      description is generated for each object. All further operations are reduced to
      the transformation of the textual data. This approach makes it possible to
      accumulate information of diverse types and efficiently analyze it according to
      the universal scheme.

PMID- 9929925
TI  - [The stepwise statistical analysis of free behavior in rats].
AB  - Logically justified sequential application of a number of statistical methods
      makes it possible to describe comprehensively free behavior of animals. In
      particular, only in the free behavior experiments it was shown that some
      behavioral indices of August rats were less variable than those of Wistar rats.
      Moreover, the results of statistical analysis suggest that August rats are less
      resistant to stress than Wistar. Additional studies had to be conducted earlier
      in order to draw the analogous conclusions. On the basis of application of
      correlation and multivariate statistical analysis it was shown that the
      horizontal motor activity can be the most important characteristic describing the
      free behavior due to its maximal informativity.

PMID- 9929926
TI  - [The concepts of quantum theory can be introduced into psychophysiology].
AB  - There are some ideas in the quantum mechanics, which may be assimilated by
      psychophysiology. The concept of interference alternatives, advanced by Richard
      Feynman, may extend the subject matter of the notion of need. The quantum theory
      assumes virtual transitions. The idea of the physical virtual process may be the
      rational basis for subjective reality.

PMID- 9929927
TI  - [Psychological factors and heart diseases].
AB  - We are often faced with patients with increased psychosocial stress, anxiety and
      depression and various cardiovascular symptoms such as hypertension, tachycardia,
      arrhythmia and chest pain. Psychological factors are important in particular in
      ischaemic heart disease and in arterial hypertension. In this respect chronic as
      well as acute stress plays a part. The problem of stress as a risk factor of
      these diseases of civilization is investigated. Some psychopathological signs may
      lead first to cardiological examination but their origin is within the psychic
      sphere of the patient. In the diagnostic sphere of some diseases which belong
      primarily into the cardiological or psychiatric sphere collaboration at a
      scientific as well as practical level is necessary.

PMID- 9929928
TI  - [Evaluation of long-term monitoring of glomerular filtration in individuals with
      kidney transplantation].
AB  - BACKGROUND: Long-term follow-up of the glomerular filtration rate (GFR) in
      subjects with a transplanted kidney revealed that changes of this function in the
      course of time are frequently irregular and cannot be expressed by a simple
      mathematical function. This fact causes problems when evaluating the rate of
      progression of chronic transplant nephropathy. Characterization of changes of the
      GFR of the graft by values of this function at the beginning and at the end of
      the follow-up period does not take into account transient changes and the
      predominating level of GFR during the entire follow-up period. The authors tried
      to elaborate a method which would render it possible to evaluate in a simple
      manner the level of the GFR during the entire investigation period. The method is
      based on assessment of the area under the curve (AUC) of GFR. METHODS AND
      RESULTS: This method was used to investigate the time course of GFR in 22
      subjects after transplantation of the kidney from a cadaverous donor. The
      investigated group included nine women and 13 men aged 30-65 years (mean 50
      years). The time interval after transplantation was 1-84 months (mean 22 months).
      The GFR was assessed after 3-months intervals for a period of 9-21 months (mean
      13.5 months). GFR was assessed on the basis of renal clearance of polyfructosan.
      The time course and level of GFR was evaluated in the common way based on GFR
      values at the beginning and end of the investigation period and according to the
      new method based on calculation of AUC. It was found that the two methods of
      evaluation of graft function do not provide the same results. In one third of the
      examined subjects the differences were higher than 20%. CONCLUSIONS: The results
      of this study provide evidence that evaluation of changes and the level of the
      GFR of the graft throughout the follow-up period based on AUC provides more
      detailed information then evaluation of the GFR only at the beginning and end of
      the follow-up period. The authors assume that this method of evaluation of the
      GFR of the graft could be helpful in a more accurate assessment of the effect of
      different therapeutic procedures.

PMID- 9929929
TI  - [Will administration of omega-3 unsaturated fatty acids reduce the use of
      nonsteroidal antirheumatic agents in children with chronic juvenile arthritis?].
AB  - BACKGROUND: An increased intake of omega-3 polyunsaturated fatty acids (PUFA) in
      the diet of patients with rheumatoid arthritis has a favourable effect on the
      course of the disease. The objective of the present work was to assess the effect
      of such a diet on the daily consumption of non-steroid antirheumatic drugs in
      children with juvenile chronic arthritis. METHODS AND RESULTS: A group of 23
      children with the diagnosis of chronic juvenile arthritis was divided by the
      method of random numbers into two groups. The first group received in addition to
      ibuprofen treatment a diet with an increased content of omega-3 PUFA. The second
      group served as control. In the first group (13 patients, mean age 11 years) in
      the course of five months treatment the original ibuprofen consumption declined
      by 17.3% (from a mean value of 28.4 mg/kg/day to 23.4 mg/kg/day), while in the
      control group (10 children, mean age 9.1 years) there was a decline of 6.5% (from
      a mean value of 23.7 mg/kg/day to 22.7 mg/kg/day). This difference was
      statistically significant at the level of 0.05 (P = 0.03). CONCLUSIONS: Despite
      the statistically significant difference in the decline of daily consumption of
      the non-steroid antirheumatic drug in the investigated groups of patients and the
      obvious favourable effect of omega-3 PUFA the mean consumption of the drug
      remained in the first group after five months of treatment higher (23.4
      mg/kg/day) than in the control group (22.4 mg/kg/day).

PMID- 9929930
TI  - [Soluble adhesive molecules and cytokines in patients with myasthenia gravis
      treated with plasmapheresis].
AB  - BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients
      with myasthenia gravis (MG) refractory to common therapy and/or with life
      threatening respiratory complications. Except from acetylcholine receptor
      antibodies (AChRAb) some other inflammatory mediators possibly activated in MG
      may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble
      adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2
      (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients
      (pts) with MG indicated to the treatment with PE. Pts were subdivided on the
      basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts
      with high AChRAb). Soluble adhesion molecules and cytokines were measured before
      the 1st and last PE, at the end of the 1st PE and in the samples of plasma
      filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher
      serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the
      first PE and the course of PE led to the substantial decrease of serum levels of
      AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not,
      however, significantly influenced by both the single and the course of PE. There
      were high levels of AChRAb, soluble adhesion molecules and soluble cytokine
      receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher
      serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS:
      Increased serum levels of soluble adhesion molecules and soluble cytokine
      receptors in pts with MG indicated to the treatment by PE suggest some systemic
      activation of immune response which is more pronounced in pts with high
      circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion
      molecules due to their effective filtration, but, on the other hand, serum levels
      of soluble cytokine receptors were not influenced by PE, in spite of their
      effective filtration which is probably counteracted by their increased
      production, possibly stimulated by the contact of the blood with synthetic
      membrane.

PMID- 9929931
TI  - [Progression of multiple myeloma during treatment with recombinant G-CSF and
      absence of G-CSF and IL-6 cell surface receptors on malignant cells].
AB  - Recombinant human hematopoietic growth factors are widely used in the treatment
      of multiple myeloma (MM) especially due to the increasing role of autologous
      blood stem cell transplantation (ABSCT). We report a patient with MM in whom
      rapid extramedullary progression of disease was observed during stem cell
      mobilization with G-CSF. In 56-year-old man with relapsing IgG lambda MM
      myeloablative therapy with ABSCT was planned 2 years after diagnosis. G-CSF is
      increasing doses was used for mobilization. Ten days after the start of G-CSF
      therapy 2 extramedullary (subcutaneous) myeloma infiltrates appeared. For the
      second mobilization high dose cyclophosphamide and VP-16 with subsequent G-CSF
      was used. During the time of chemotherapy tumour infiltrates disappeared,
      however, after one week of G-CSF treatment rapid progression of disease with the
      formation of multiple extramedullary infiltrates occurred and the patient died in
      June 1996. Small pieces of subcutaneous tumour infiltrates were removed at
      autopsy and immediately frozen in liquid nitrogen. Using the panel of specific
      antibodies the expression of cytokine receptors (IL-1, 2, 3, 6, 7, 8, 10, SCF,
      gp130, G-CSF, GM-CSF, EPO) and Fas, Pgp and 24-34 kD multidrug resistance
      associated protein were examined. However, no expression of cytokine receptors on
      tumor cells was found. On the contrary, high positivity of surface MDR associated
      proteins was observed.

PMID- 9929932
TI  - [Acute anxiety and its therapy].
AB  - Acute anxiety is a quite common event for a general practitioner to solve.
      Anxiety could be of a various ethiology and the treatment should be based on the
      ethiology. It is important to differentiate panic attacks from general anxiety so
      as panic disorder treatment differs specifically. The drug of choice for
      parenteral application for acute anxiety seems to be diazepam in the Czech
      republic conditions and the most convenient drug for oral administration is
      alprazolam.

PMID- 9929933
TI  - [The HELLP syndrome].
AB  - The HELLP syndrome is a serious complication of pregnancy, found most frequently
      in conjunction with severe preeclampsia. The incidence of this disease in
      preeclampsia is between 2 and 12%. The diagnosis is based on typical laboratory
      findings, i.e. haemolysis--H, elevated liver enzymes--EL and a low-platelet count
      -LP. Haemolysis is defined as microscopic finding of an abnormal peripheral blood
      smear, elevated total bilirubin above 1.2 mg/dl and elevated lactate
      dehydrogenase above 40 mukat/l. Transaminases (AST above 4.2 mukat/l) are also
      elevated. For HELLP a low platelet count is typical (number of thrombocytes less
      than 100,000 mm3). The symptoms include above all pain in the epigastrium, in the
      right subcostal area, nausea and vomiting. Non-specific symptoms resembling
      viroses are lassitude, general weakness, headache and fatigue. A correct
      differential diagnosis and early assessment of the diagnosis are decisive for
      starting treatment which can prevent the development of serious complications
      such as disseminated intravascular coagulopathies and hepatorenal failure.
      Treatment of the HELLP syndrome is symptomatic with the objective to stabilize
      the general condition of the mother, improved haemodynamic conditions and the
      impaired haemocoagulation. A very important therapeutic step is early termination
      of pregnancy which depends on ther mother's condition and the condition of the
      foetus with regard to gestational age.

PMID- 9929934
TI  - [Selective estrogen receptor modulators as a new concept in preventing health
      risks of menopause].
AB  - Long-term estrogen deficiency after menopause is responsible for different
      disorders, which not only make the quality of life in the older age worse but
      also are the major causes of women's mortality. It is especially the case for
      cardiovascular disease, osteoporosis and dementia. The risk for these disorders
      can significantly be reduced by hormone replacement therapy (HRT). Unfortunately,
      the mean duration of the postmenopausal administration of HRT is too short to
      demonstrate its efficacy in preventing the mentioned diseases. In this review the
      new therapeutic possibilities are discussed, called selective estrogen receptor
      modulators (SERMs). These structurally heterogeneous compounds interact with
      estrogen receptors and act as either estrogen-agonists or--antagonists according
      to the type of organ and physiological context (i.e., dose, target tissue and
      hormone concentration in the tissue). The evaluation of the effects of these
      compounds led to the better understanding of both antiestrogens and the whole
      steroid signaling system. The research of the clinical properties of SERM showed
      their potential benefit in the long-term care of the women in their non
      reproductive period of life and demonstrated the possibility to overcome some
      drawbacks of HRT.

PMID- 9929935
TI  - [Repeat kidney transplantation].
AB  - BACKGROUND: The objective of the study was an analysis of results of repeated
      kidney transplantations (Tx2, Tx3) implemented during the first 29 years of
      activities of the Transplantation Centre of the Institute of the Clinical and
      Experimental Medicine in subjects with a different maintenance immunosuppression.
      METHODS AND RESULTS: The retrospective study pertains to 134 Tx2 and 17 Tx3 in
      134 non-diabetic subjects: 43 of them had during Tx1 and Tx2 (1966-1981 and 1966
      1985 resp.) immunosuppression on the basis of azathioprin (Aza, sub-group AA), 42
      during Tx1 (1972-85), Aza, while during Tx2 (1984-85) immunosuppression on the
      basis of cyclosporin (CyA, subgroup AC) and 49 both during Tx1 and Tx2 (1985-93
      and 1986-95 resp.) CyA (subgroup CC). Compared was survival of grafts by the
      actuarial method (with regard to all losses regardless of cause) by the end of
      the 4th year inside the subgroups (Tx2, vs. Tx1 and Tx3 vs. Tx2 in the same
      subjects) and between subgroups (Tx1 vs. Tx1 and Tx2 vs. Tx2 in different
      subjects). Moreover in paired investigations the survival of recipients and
      grafts after Tx2 was compared after immunosuppression on the basis of CyA with
      the same parameters after Tx1 in different subjects with the same
      immunosuppression, operated at approximately the same time (n = 81) and survival
      of subjects with Tx1 + Tx2 on the CC regime regardless whether the second grafts
      functioned at the time of the last examination, with survival of subjects after
      Tx1 where after graft failure Tx2 was not performed (n = 34). Prophylaxis with
      antilymphocyte globulins was not used. Survival of second and first grafts did
      not differ in any of the subgroups, third grafts survived at the end of the third
      year more frequently than second grafts (66 vs. 18%, p < 0.01). Second grafts in
      CC survived more than in AA (55 vs. 28%, p < 0.01). In the paired study Tx2 vs.
      Tx1 the survival of grafts and recipients was the same (88 vs. 89%, N.S. and 47
      vs. 62% resp.), in the paired study Tx1 + Tx2 vs. Tx1 more subjects with Tx1 +
      Tx2 survived 10 years after Tx1 than subjects who did not have Tx2 (82 vs. 49%, p
      < 0.05). CONCLUSIONS: A further transplantation of the kidney after functional
      loss of the first graft is the method of choice: the mortality is low, the
      probability of several years' function is considerable and the prognosis as
      regards quality and length of life better than with regular dialysis treatment.

PMID- 9929936
TI  - [Can normalization of vascular cytoadhesive activity be explained by the anti
      atherosclerosis effect of growth hormone?].
AB  - BACKGROUND: The increased mortality caused by premature atherosclerosis has been
      shown among patients with hypopituitarism receiving conventional hormone
      treatment but with unsubstituted growth hormone deficiency. This experience
      belongs among the most important arguments in favour of replacement with growth
      hormone. The mechanisms of the antiatherogenic effect of growth hormone are
      poorly understood. The protective effect of growth hormone on the vascular
      endothel and its intervention in the clotting process, which have not been yet
      elucidated, may be the causative factors. METHODS AND RESULTS: The endothelial
      damage as given by measuring of circulating soluble cytoadhesive molecules sE
      selectin, sP-selectin and intercellular adhesive molecule 1 (ICAM 1) was measured
      in 15 adult panhypopituitaric patients before and after 1 year treatment with
      recombinant human growth hormone. The blood levels of all of these cytoadhesive
      molecules decreased significantly (p < 0.01) during the treatment. None of the
      concomitantly followed coagulation tests (prothrombin time, activated partial
      thromboplastin time, fibrinogen, antithrombin III, von Willebrand's factor and D
      dimer) was significantly changed during the treatment. The tendency to decrease
      (p = 0.054) was observed with antithrombin III. CONCLUSIONS: The decrease of
      circulating cytoadhesive molecules in blood during the treatment of growth
      hormone gives evidence for its protective effect, either direct or mediated, on
      the vascular endothel. These findings could bring an explantation for the
      premature atherosclerotic changes in hypopituitarism and antiatherogenic effect
      of growth hormone.

PMID- 9929938
TI  - [Bird's eye view of laboratories--report on symposia].
AB  - "Biochips" technology starts entering DNA laboratories and not only as
      prototypes, that show fascinating increase in effectivity which can change our
      nearest future. Practically all processes used in DNA laboratories are to be
      involved. Hybridization reaction is the most often used principle in microchips,
      but already polymerase chain reaction (PCR) has been miniaturized to the
      microchip level and also separation of blood cells. Function of these newly
      developed microdevices in being verified by solving practical problems in
      diagnostics.

PMID- 9929937
TI  - [Treatment of febrile neutropenia in patients with solid tumors].
AB  - BACKGROUND: Febrile neutropenia (FN) is one of the most serious complications of
      anti-tumourous treatment calling for early diagnosis and intensive treatment. The
      objective of the trial was to recommend a standard procedure for the treatment of
      febrile neutropenia at their Oncological Clinic, based on analyses of attacks of
      febrile neutropenia and the current microbial situation. METHODS AND RESULTS: In
      1995-1997 in 30 patients (24 women, 6 men) 39 attacks of febrile neutropenia were
      treated. The age distribution of patients was within the range of 20-68 years,
      the mean age being 50 years. In the group patients with breast cancer
      predominated (14), soft tissue sarcomas (4), colorectal carcinoma (3), other
      diagnoses participated with 9 episodes. The analysis of the microbial situation
      was based on cultivation findings made in patients with attacks of FN. For
      empirical treatment of FN the authors use at combined treatment piperacillin
      gentamicin or sultamicillin-cefpodoxim/or ciprofloxacin. If empirical treatment
      fails, therapy is based on the results of cultivation and the patient's clinical
      condition. Growth factors are indicated for treatment only in FN complicated by
      mycotic infection, inflammatory pulmonary infiltrates or cardiopulmonary failure.
      CONCLUSIONS: The standard procedure in the treatment of FN should be broad
      spectrum bactericidial antibiotics. The use of growth factors is reserved for
      complicated episodes of FN.

PMID- 9929939
TI  - Ultrastructural observations on neuroblastic tumors in childhood: a study of
      tumor cell differentiation and regression on 89 cases.
AB  - The study presents ultrastructural findings in 89 neuroblastic tumors. All of
      them including 21 undifferentiated neuroblastomas (NB) were characterized by
      neural cell processes which contained neurofilaments, mitochondria and
      neurosecretory granules. The granules were generally sparse and their number and
      distribution was a feature independent on other signs of differentiation of the
      tumor cells. We found degenerative changes in the tumor cell bodies and their
      neuronal processes to be a prominent phenomenon in neuroblastic tumors. Although
      they occurred both in patients who were operated primarily and in those who
      received a preoperative chemotherapy they were most conspicuous in the latter
      group (28 of 80 patients). The degenerative changes included swelling and
      dilatations of the neuronal processes, accumulation of heterophagosomes,
      myelinated bodies and cytoskeletal filaments. Some ganglion cells had dilated
      endoplasmic reticulum, and contained lipofuscin. In one ganglioneuroblastoma we
      detected dense granulated bodies resembling neuromelanin. The diagnosis of
      undifferentiated NB was established on the basis of ultrastructural
      investigations in 13 out of 21 undifferentiated NB; in the remaining 8 cases the
      electron microscopy was an additional confirmatory tool together with the results
      of immunohistochemical reactions. The electron microscope is still a valuable
      instrument for diagnosis of neuroblastic tumors in addition to newer diagnostic
      approaches such as immunohistochemical and molecular investigations.

PMID- 9929940
TI  - [Detection of monoclonality in childhood lymphoma with the polymerase chain
      reaction].
AB  - We studied monoclonality of tumour cells by polymerase chain reaction (PCR) in
      paediatric lymphomas. In B-lymphomas we detected monoclonal rearrangement of the
      immunoglobulin of the T-cell receptor delta and gamma chain (TCR, TCR-delta, TCR
      gamma) by an analogous way. We examined a group of 37 paediatric patients with
      lymphomas (26 with B-lymphomas and 11 with T-lymphomas). Monoclonal gene
      rearrangement was found in 34 cases, i.e. the method used in this study proved to
      be successful in 92% of cases. We confirmed our results by correlation with
      histologic and immunohistologic diagnoses. The method may be used as a
      complementary diagnostic tool in differential diagnosis of lymphoma versus non
      neoplastic proliferation of lymphatic tissue, in distinction between B- and T
      lymphomas, and to separate lymphomas and other malignancies. Beside the pure
      diagnostic usage we perceive the main importance of the method in monitoring
      minimal residual disease (MRD), because amplified products of PCR may be
      sequenced and used for preparing tumour specific primers and probes.

PMID- 9929941
TI  - [Expression of the nm 23 gene in pulmonary carcinomas].
AB  - Gene nm 23 may have an antimetastatic function but relevant data in the
      literature are ambiguous even in the same types of malignant tumors. In a group
      of 77 lung carcinomas there was not found any relation of gene nm 23 expression
      to the histologic type of tumor or the level of its differentiation and to the
      finding of metastases in resected lung materials either. Adenocarcinomas showed a
      negative relation of nm 23 expression to later occurrence of metastases and to a
      decreased survival of patients which squamous, neuroendocrine and
      undifferentiated carcinomas did not. Unexpected low expression or negativity of
      nm 23 in tumors of little progression and rare high positivities in some lung
      carcinomas with metastases could be explained by gene nm 23 mutations or
      inactivation. Results of the study do not encourage the usage of nm 23 as a
      reliable prognostic marker in lung carcinomas.

PMID- 9929942
TI  - [Low grade malignant fibromyxoid sarcoma].
AB  - Two cases of low-grade fibromyxoid sarcoma are presented. In a 31-year-old male
      the tumour arouse in the scapular soft tissues and local recurrence occurred. In
      a female of 45, the neoplasm was located in the thigh. Histologically, the
      neoplasms with low cellularity of deceptively benign-appearing small fibroblastic
      spindle cells demonstrated alternating dense fibrous and loose myxoid areas,
      showing a mainly whorled and swirling growth pattern. In myxoid areas a prominent
      vascular component was present. Mitoses and cellular atypia were absent. Tumor
      cells showed staining with anti-vimentin and occasionally anti-actin antibodies.
      As a distinctive soft-tissue sarcoma, low-grade fibromyxoid sarcoma had to be
      distinguished from variety of benign and malignant soft tissue tumours such as
      neurofibroma, liposarcoma, myxoid MFH and others.

PMID- 9929943
TI  - [Inflammatory stromal reaction in epithelial neoplasia of the uterine cervix in
      correlation with HPV infection].
AB  - 260 cases of women with epithelial neoplasias of the uterine cervix were studied:
      HPV infection was detected by DNA in situ hybridization and serology,
      simultaneously structure and intensity of stromal inflammatory reaction (SR) were
      evaluated (semiquantitatively) as well as standard clinical immunological
      parametres investigated by serology. Results proved the same character of SR in
      intraepithelial lesions and invasive carcinomas and the intensity of SR
      increasing in relation to the gravity of epithelial dysplasia. There was not
      found any significant difference in SR between cases with detected HPV infection
      and cases lacking it. Summarized immunological parametres were in limits of
      normal reference range.

PMID- 9929944
TI  - [An imaging system and computer processing of digital images from the Tesla BS500
      transmission electron microscope].
AB  - Original digital image acquiring system for electron microscope TESLA BS500 was
      developed. Optical image from yttriumgarnet monocrystal was captured by TV CCD
      bottom mounted camera and processed by computer with software Video TIP. Repeated
      image acquisition enabled substantial improving of signal/noise ratio. Image
      element of 42 microns diameter was achieved. The system is ready for additional
      innovation, especially with a high performance CCD camera.

PMID- 9929945
TI  - [Over a half century at the 1st Medical School of Charles University: development
      of interdisciplinary cooperation].
AB  - A vast interdisciplinary and methodological cooperation became a leading feature
      of pathology. It brought critical evaluation and synthesis of data from several
      points of view without prevalence of a pure structural empirism. Nevertheless,
      detailed structural analysis remains an unmatched and effective introductory way
      of diagnostic algorithms. A wide methodology is not always useful in its capacity
      but should be open to each of teachers. For the time being we rely more on
      outstanding personalities. Call for them as well as their reasonable uniting may
      restore the original sense to the School Scientific Council.

PMID- 9929947
TI  - [The characteristics of the bioelectrical activity of symmetric areas of the
      human cerebral cortex after weak transcutaneous stimulation of the optic nerve].

PMID- 9929946
TI  - [The presaccadic potentials of the human brain during the stimulation of the
      leading and nonleading eyes].

PMID- 9929948
TI  - [The role of the right and left cerebral hemispheres in space perception. II.
      Depth perception as an interhemispheric phenomenon].

PMID- 9929949
TI  - [The season of birth and laterality].

PMID- 9929950
TI  - [The perception of the frequency of tonal stimuli in a lesion of the sound
      perceiving apparatus].

PMID- 9929951
TI  - [The dynamics of the rhythmic EEG components during relaxation in 9- to 10-year
      old schoolchildren with different learning achievements].

PMID- 9929952
TI  - [The late-period characteristics of the bioelectrical activity of the brain in
      participants in the cleanup of the aftermath of the accident at the Chernobyl
      Atomic Electric Power Station].

PMID- 9929953
TI  - [The dependence of the characteristics of the heart rate and blood flow on age in
      healthy subjects and patients with cardiovascular diseases].

PMID- 9929954
TI  - [A dynamic analysis of heart rate variability during hyperventilation].

PMID- 9929955
TI  - [The effect of a repeated stay in a hypercapnic environment on the properties of
      the respiratory system].

PMID- 9929956
TI  - [The effect of different types of weather on the external respiratory indices of
      young healthy subjects].

PMID- 9929957
TI  - [The current problems of space medicine and physiology (on the 95th birthday of
      V. V. Parin)].

PMID- 9929960
TI  - [The omega-potential in studies of the compensatory-adaptive body reactions of
      sailors during a prolonged cruise].

PMID- 9929958
TI  - [The chronobiological monitoring of health status and the cleanliness of the
      environment].

PMID- 9929959
TI  - [The viability and thermostability of human lymphocytes with varying resistance
      to heat exposure].

PMID- 9929961
TI  - [A comparative assessment of the biotransformational and pharmacokinetic
      activities of the liver in inhabitants of the tropics and middle latitudes during
      adaptation in the Polar region].

PMID- 9929962
TI  - [Erythrocyte electrophoretic mobility and stress].

PMID- 9929963
TI  - [Laser-Doppler flowmetry and the analysis of the collective processes in the
      microcirculation system].

PMID- 9929964
TI  - [The effect of melatonin on thrombocyte aggregation in healthy subjects].

PMID- 9929965
TI  - [The effect of Manchurian aralia on fluctuations in the individual minute value].

PMID- 9929968
TI  - Repeat-directed isolation of a novel gene preferentially expressed from the
      maternal allele in human placenta.
AB  - Using a repetitive sequence of tandemly arrayed pentanucleotides in the human H19
      3'-flanking region, we isolated a phage clone (lambda PEN11) which localized to
      chromosome 11p15.5. The lambda PEN11 phage encodes a 2.3-kb cDNA consisting of
      seven exons at least. The gene was mainly expressed in brain and pancreas (and
      less abundantly in testis), and demonstrated differential allele usage, with
      maternal expression being predominant in placenta, which indicates the gene is an
      atypical imprinted gene. While the pentamer repeat might contribute to this
      effect, it is also possible that the differential allele usage might reflect the
      local chromosomal structure known as the imprinting domain.

PMID- 9929969
TI  - Genome-wide scanning for type 2 diabetes susceptibility in Canadian Oji-Cree,
      using 190 microsatellite markers.
AB  - We undertook a genome-wide scan using 190 markers with an average separation of
      20 cM in 49 Canadian Oji-Cree sib pairs affected with type 2 diabetes. Four of
      these markers, one each on chromosomes 6, 8, 16, and 22, showed both suggestive
      linkage and suggestive association with type 2 diabetes in the Oji-Cree. None of
      these markers corresponded to any chromosomal region or marker that has so far
      been linked with type 2 diabetes in other populations. Thus, there might be
      several genetic loci that confer susceptibility to type 2 diabetes in this study
      sample. We are following up on these preliminary leads by increasing the density
      of the markers within these linked and associated regions, and also by increasing
      the number of study subjects. Also, we found instances in which there were wide
      disparities between the Oji-Cree and reference Caucasians with respect to marker
      heterozygosity. This suggests that a particular set of markers for genome-wide
      scanning will have different informativeness in different ethnic groups. Thus,
      different marker sets will likely be required for different ethnic groups in
      order to maximize their information content for linkage calculations.

PMID- 9929970
TI  - Anxiety traits associated with a polymorphism in the serotonin transporter gene
      regulatory region in the Japanese.
AB  - We determined polymorphism in the serotonin (5-HT) transporter gene-linked
      polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the
      polymerase chain reaction of Lesch et al., with minor modifications. The
      distribution of allele frequencies was determined and found to differ from that
      in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR
      to anxiety traits, by having 189 of the 501 subjects complete a self-rating
      questionnaire for anxiety and depression. Subjects with the short/short (s/s)
      genotype had significantly higher anxiety scores than those with the long/long
      (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of
      5-HTTLPR have stronger anxiety-related personality traits than those with the 1
      allele.

PMID- 9929971
TI  - Germline mutations in a polycytosine repeat of the hMSH6 gene in Korean
      hereditary nonpolyposis colorectal cancer.
AB  - Somatic mutations within a mononucleotide repeat sequence present in the hMSH6
      and hMSH3 coding regions have been frequently observed in various human cancer
      tissues and cell lines showing genomic instability. However, relatively few
      germline mutations of the repeat sequence have been identified. Two germline
      mutations in the hMSH6 region have been reported in hereditary nonpolyposis
      colorectal cancer (HNPCC); however, no germline mutations in the hMSH3 gene have
      been reported yet. To investigate genetic alterations within an 8 bp polycytosine
      repeat of the hMSH6 gene and an 8-bp polyadenine repeat of the hMSH3 gene, we
      amplified the mononucleotide repeat sequences of 35 HNPCC patients, 44 patients
      suspected of having HNPCC who did not fulfill the criteria of the International
      Collaborative Group on HNPCC, and 45 patients with sporadic early-onset
      colorectal cancer who developed colorectal cancer before the age of 40 years
      without any family history of colorectal cancer. Genetic alteration of the repeat
      sequence of the hMSH3 gene was not observed, whereas germline frame-shift
      mutations (one C insertion) in the hMSH6 gene were found in two of the 44
      suspected HNPCC patient in whom germline mutations of hMSH2 or hMLH1 had not been
      detected. An identical frameshift mutation was also observed in another affected
      member of a suspected HNPCC family. These results suggest that the mutation of
      hMSH6 is responsible for tumorigenesis in minor groups of suspected HNPCC
      patients.

PMID- 9929972
TI  - Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine
      diphosphate-glucuronosyltransferase gene in Japanese.
AB  - Neonatal hyperbilirubinemia, which is prevalent among Asian peoples, has been
      considered as a physiological phenomenon, and its metabolic basis has not been
      clearly explained. Gilbert syndrome is a common inherited disease of unconjugated
      hyperbilirubinemia due to decreased bilirubin uridine diphosphate
      glucuronosyltransferase (B-UGT), and its role in neonatal jaundice has recently
      been considered. We have previously reported that the Gly71Arg mutation of the B
      UGT gene associated with Gilbert syndrome is prevalent in Japanese, Korean, and
      Chinese populations and was more frequently detected in neonates with severe
      hyperbilirubinemia than in control subjects. We have studied 159 Japanese full
      term neonates, evaluating the relationship between the B-UGT genotype and the
      severity of jaundice, as assessed with a transcutaneous bilirubinometer. The gene
      frequency of the Gly71Arg mutation in these neonates was 0.19, and neonates
      carrying the Gly71Arg mutation had significantly increased bilirubin levels on
      days 2-4, manifested in a gene dose-dependent manner. The frequency of the
      Gly71Arg mutation was 0.47 in the neonates who required phototherapy (i.e., those
      with more severe hyperbilirubinemia), significantly higher than 0.16 in the
      neonates who did not require the therapy. The gene frequency of the TA repeat
      promoter polymorphism, the (TA)7 mutation, was 0.07, and neonates carrying this
      mutation did not have an increase in bilirubin. These results suggested that the
      Gly71Arg mutation contributes to the high incidence of neonatal
      hyperbilirubinemia in Japanese.

PMID- 9929973
TI  - Allelic variations of the D2 dopamine receptor gene in children with idiopathic
      short stature.
AB  - The D2 dopamine receptor (DRD2) plays a major role in growth hormone (GH)
      secretion. Recent reports indicate that Taq I A DRD2 gene alleles (A1 and A2) are
      related to the function of DRD2. Idiopathic short stature (ISS) is defined as
      short stature without accompanying malnutrition, chronic disease, and
      endocrinological disorders. However, some reports suggest that ISS is associated
      with a mild disturbance of GH secretion. In this study, we examined the notion
      that allelic variants of the DRD2 are associated with ISS. We studied 55 children
      with ISS aged 8.4 (SD 2.9) years; (group I) and 104 age-matched children of
      normal stature (group II). Informed consent was obtained from each child's parent
      or guardian. Genomic DNAs were extracted from peripheral mononuclear cells and
      amplified by polymerase chain reaction (PCR). The PCR products were digested by
      Taq1 and resolved by electrophoresis. The frequency of the A1 allel was
      significantly higher in group I (0.42) than in group II (0.26). The insulin-like
      growth factor (IGF)-I ratio (the ratio of the individual level to the normal mean
      value according to age at our laboratory center) was significantly lower in group
      I than in group II. When group I was subdivided into group A (with the A1 allele)
      and group B (with only the A2 allele), group A had a significantly lower peak GH
      response to the l-dopa test, lower levels of IGF-I, and retarded bone maturation.
      These findings indicate that polymorphism of the DRD2 gene may be one genetic
      factor that affects body height in childhood, acting through the hypothalamus (GH
      releasing hormone)--pituitary (GH)--IGF-I axis.

PMID- 9929974
TI  - Prevalence of congenital malformations and genetic diseases in Korea.
AB  - A nationwide investigation of congenital malformations and genetic diseases in
      Korea was conducted by analyzing Medical Insurance data for infants aged under 1
      year. Medical Insurance data were obtained for 1993 and 1994 and the ICD-9
      (International Classification of Diseases, Ninth Revision) code was used to
      classify the diseases. The coverage rate of medical insurance was approximately
      95% of the total population. Anomalies of the cardiovascular, musculoskeletal,
      and gastrointestinal systems, in descending order of frequency, were more
      frequent than anomalies in other systems. The average prevalence of
      cardiovascular anomalies for 1993 and 1994 was 15 per 1000 infants, and
      ventricular septal defect, with an average prevalence of about 3.50 per 1000 for
      1993 and 1994, was the most frequent cardiovascular anomaly in infants.
      Polydactyly was the most frequent musculoskeletal anomaly, with an average
      prevalence, for 1993 and 1994, of about 1.20 per 1000 infants. Anencephaly had
      the highest frequency of nervous system anomalies. Congenital hypertrophic
      pyloric stenosis was the most common of the gastrointestinal anomalies. The
      prevalence of the congenital malformations and genetic diseases examined was
      similar to that reported in other countries. Total medical expenses for the care
      of patients with each disease entity were also estimated. The highest medical
      expenses were incurred for ventricular septal defect, congenital coagulation
      factor VIII disorders, atrial septal defect, tetralogy of Fallot, and spinal
      anomalies, in descending order of magnitude. This investigation could be helpful
      in planning social welfare systems, as well as for elucidating the current status
      of congenital malformations and genetic diseases in Korea, and in other Asian
      countries.

PMID- 9929975
TI  - Molecular analysis of methylmalonyl-CoA mutase deficiency: identification of
      three missense mutations in mut0 patients.
AB  - Genetic defects in the methylmalonyl-CoA mutase (MCM) gene cause methylmalonic
      acidemia (MMA). Only three mutations have been reported among Oriental patients
      to date. We studied fibroblast cell lines established from three Japanese
      patients with MCM deficiency. Enzymatic study showed that these patients had the
      muttype of MMA. Nucleotide sequencing of MCM cDNAs identified three missense
      mutations: a T to A change at nucleotide position 2082, which results in an amino
      acid substitution of Glu669 for valine (V669E); a T to A change at position 1179
      with the corresponding amino acid substitution of Asp368 for valine (V368D); and
      a G to A change at position 1182 with the corresponding amino acid substitution
      of His369 for arginine (R369H). Each of the three missense mutations abolished
      MCM activity according to a transient expression study. Alignment of these
      mutations with a recently reported homology model of human MCM allowed us to
      speculate on the effect of these nonconservative amino acid substitutions on MCM
      activity: V368D and R369H affected residues in the beta/alpha-(TIM-) barrel
      domain, on one of the two alpha-helices that form the dimer interface, while
      V669E altered a residue in the adenosylcobalamin-binding domain in the C
      terminus.

PMID- 9929976
TI  - No latent chromosome damage in oxygen-exposed premature neonates.
AB  - The possible effect of in vivo oxygen exposure on chromosomes was examined in
      lymphocyte cultures of 12 very-low-birthweight infants on the 1st, 8th, and 16th
      days of intensive care. No increase of cytogenetic anomalies was seen in
      untreated and bleomycin-treated cultures. The findings suggest that neonatal
      oxygen exposure is unlikely to cause latent chromosome damage.

PMID- 9929977
TI  - Novel germline mutations of the MEN1 gene in Japanese patients with multiple
      endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder
      characterized by tumors of the parathyroid glands, the pancreatic islet cells,
      and the anterior pituitary. Germline mutations of the MEN1 gene in three
      independent Japanese cases with MEN1 were analyzed. Case 1 has revealed a 2-bp
      (TA) insertion at nucleotide position 341 (341insTA) in exon 2, which shifts the
      reading frame such that the mutant protein has a completely different amino acid
      sequence from codon 78 to the premature stop codon at 119. In case 2, a
      nucleotide substitution, i.e., TAG in place of TGG, which encodes tryptophan at
      codon 198 was identified (nonsense mutation). These mutations were heterozygously
      present and have not been reported previously. Case 3 showed no mutations in the
      protein-coding exons and exon-intron junctions of the MEN1 gene by single-strand
      conformation polymorphism or direct sequencing of the polymerase chain reaction
      (PCR) fragments. We confirmed the finding that patients with MEN1 carry
      heterozygous germline mutations in the MEN1 gene, which is compatible with the
      idea that the MEN1 gene is a tumor suppressor gene. The reason why mutations in
      the coding region of the MEN1 gene could not be detected by PCR-based analysis in
      some of the MEN1 patients, e.g. case 3, needs to be clarified further.

PMID- 9929978
TI  - Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese
      patients.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder characterized by
      pancytopenia, predisposition to cancers, and a diverse variety of congenital
      malformations. At least eight complementation groups, A through H, have been
      described. Recently, the FA-A gene (FAA) has been isolated, and a large number of
      distinct mutations reported in ethnically diverse FA-A patients. Here, we report
      on the mutation analysis of five FA patients by single-strand conformation
      polymorphism. Out of five patients, at least three were found to have mutations
      in the FAA gene. The first patient was a compound heterozygote with a 1-bp
      deletion and a single-base substitution. The second patient had a heterozygous 2
      bp deletion, which introduces a premature termination codon, and the third
      patient had a heterozygous splice donor site mutation in intron 27.

PMID- 9929979
TI  - Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1,
      showing homology to a metastasis-associated gene, MTA1.
AB  - Through large-scale sequencing of clones randomly selected from libraries of
      human cDNAs, we have isolated a novel human gene encoding a product with 59.6%
      identity in amino acid sequence to human MTA1, a protein associated with tumor
      invasion and metastasis. This cDNA, named MTA1-L1 (MTA1 like 1), consists of 2736
      nucleotides with an open reading frame encoding 668 amino acids. A single 3.0-kb
      transcript of MTA1-L1 was expressed ubiquitously on Northern blots. Structural
      analysis of the MTA1-L1 gene revealed 18 exons spanning 8.1 kb of genomic DNA. We
      assigned the MTA1-L1 locus to chromosomal band 11q12-13.1 by fluorescence in situ
      hybridization.

PMID- 9929980
TI  - Localization of human midisatellite and macrosatellite DNA sequences on
      chromosomes 1 and X in the great apes.
AB  - The mechanism of speciation has remained largely unresolved, and hominoid
      evolutionary history based on chromosome rearrangements has been continuously
      challenged. The recent availability of the human-derived chromosome 1-specific
      midisatellite (D1Z2) and chromosome X-specific macrosatellite (DXZ4) DNA sequence
      probes has prompted us to hybridize the aforementioned to the members of the
      hominoid clade (chimpanzee, gorilla, and orangutan), using the fluorescence in
      situ hybridization technique. Inconsistencies in the hybridization pattern for
      the D1Z2 DNA probe in the great ape species suggests that changes in this
      sequence have apparently taken place during the evolutionary process. No
      hybridization signal was observed in the orangutan chromosome 1, suggesting that
      a homologous D1Z2 DNA sequence may not be present in its genome, or that the
      sequence may be altered, rendering itself undetectable by human-derived DNA
      probes. Homology in the hybridization patterns for the DXZ4 probe in all three
      ape species illustrates that the sequence is apparently conserved. Such
      hybridization data provide some level of phylogenetic information on the recent
      ancestry of higher primates.

PMID- 9929981
TI  - Autosomal dominant onychodystrophy and congenital sensorineural deafness.
AB  - The disease "deafness and onychodystrophy" (DOD) is characterized by congenital
      hearing impairment and dystrophic or absent nails and teeth. The autosomal
      dominant form of the disorder has been previously reported only in one family. We
      describe here another family in which three members in three generations (a girl,
      her mother, and her maternal grandfather) were affected with DOD. Our finding is
      consistent with an autosomal dominant mode of inheritance and confirms autosomal
      dominant DOD (DDOD, MIM *124480) as a recognizable clinical entity.

PMID- 9929982
TI  - Another observation of microphthalmia in an XX male: microphthalmia with linear
      skin defects syndrome without linear skin lesions.
AB  - A case of microphthalmia with Xp microdeletion is reported. The patient was a boy
      who showed bilateral microphthalmia with corneal opacities, hypospadias without
      evidence of hypogonadism, and a conduction disturbance of the heart (Wenckebach
      conduction). No skin lesion was discerned. High-resolution chromosome analysis
      revealed the karyotype of 46,X,del(X)(p22). The phenotype was considered to be
      microphthalmia with linear skin defects (MLS) syndrome without skin lesions.
      Polymerase chain reaction and fluorescence in-situ hybridization analyses
      revealed that the chromosome aberration resulted from an X;Y translocation: the
      presence of pseudoautosomal boundary Y and the sex-determining region of Y was
      confirmed, while Xp deletion involving the region distal to DXS1129 was
      ascertained. Thus the chromosome designation using the ISCN 1995 nomenclature is
      46,X,der(X),t(X;Y)(p22.13;q11.2). Despite the absence of skin lesions, the Xp
      deletion of our patient corresponded to those of previously reported typical
      cases of MLS syndrome. Our observation further supports the current hypothesis
      that the phenotypic variation of MLS syndrome represents tissue-different X
      inactivation rather than different genetic effects of two contiguous genes.

PMID- 9929983
TI  - First case of missense mutation (LDH-H:R171P) in exon 4 of the lactate
      dehydrogenase gene detected in a Japanese patient.
AB  - Complete deficiency of lactate dehydrogenase (LDH) subunit H was identified in a
      41-year-old woman with paralysis of her left lower limb. The propositus had
      extremely low LDH activity and five of her family members had levels of LDH
      activity that ranged from lower than normal to normal level. A transversion
      mutation at codon 171 (CGC-->CCC), resulting in an Arg-->Pro substitution was
      identified in her DNA sequence. A new NruI restriction site was introduced into
      the polymerase chain reaction (PCR) product by PCR-primer introduced restriction
      analysis (PCR-PIRA) using a specific mismatched primer. Digestion with NruI
      revealed that the propositus and her mother were, respectively, homozygous and
      heterozygous for this mutation.

PMID- 9929984
TI  - Chromosomal mapping of two RBP-J-related genes: Kyo-T and RBP-L.
AB  - We have recently isolated two genes encoding proteins which have either homology
      or affinity to RBP-J, a transcription factor involved in Notch signaling. Kyo-T
      interacts with RBP-J and possibly regulates the function of RBP-J. RBP-L has a
      highly homologous region with RBP-J but the function of RBP-L is unknown.
      Fluorescence in situ hybridization analysis of human metaphase chromosomes
      localized Kyo-T and RBP-L to Xq26 and 20q12-13.1, respectively.

PMID- 9929985
TI  - A single-nucleotide polymorphism in the human bone morphogenetic protein-4 (BMP
      4) gene.
AB  - A polymorphic site has been found in the human bone morphogenetic protein-4
      (BMP4) gene. To our knowledge, it is the first defined polymorphism in this gene,
      being present with similar frequencies in Caucasian, Hispanic, and African
      populations.

PMID- 9929986
TI  - The future is in the present: the impact of generations.
AB  - Among the complex mix of forces that shape our futures are differences among
      generations. A generation is a cohort, roughly twenty-some years in duration,
      where the members have experienced a common formative environment and tend to
      react to the world in patterned fashion. The defining characteristics of five
      generations are discussed: Gl, Silent, Boomers, Generation X, and the millennial
      generation. Implications are drawn for patient preferences as dental consumers,
      recruitment and management of faculty and others in organizations, and the
      transitions of values in leadership of professional organizations.

PMID- 9929987
TI  - Current patterns and future trends in the population of the United States:
      implications for dentistry and the dental profession in the twenty-first century.
AB  - Changes in the size, distribution and composition of the population of the United
      States will have significant effects on health care professionals in the coming
      years. For dentists and other professionals involved in health care provision, it
      is likely that among the effects of demographic change will be change in the
      characteristics of their patient base, change in the characteristics of health
      professionals, and potential change in the socioeconomic resources of their
      patients. In this article, we describe current and expected future patterns of
      change in the population of the United States and discuss their significance for
      dentistry in the twenty-first century.

PMID- 9929988
TI  - Trends: immigration and technology.
AB  - America is experiencing a new wave of immigration that many say will be larger
      than the one beginning just before 1900. But this immigration is more global in
      origin and will result in making many states so diverse that there is no
      "majority" culture. Immigration will fuel the economy and will be particularly
      advantageous to those businesses that can recognize and respond to the needs of
      the new immigrant groups.

PMID- 9929989
TI  - Dental education--issues and trends.
AB  - This article is a survey of the current status and likely future changes in
      dental education in the context of changing demographics, economics, and higher
      education. Topics covered include changes in faculty, students, curriculum,
      research, and dental practice.

PMID- 9929990
TI  - Managed care: an ethical controversy in dentistry as viewed by a dental student.
AB  - This essay defines managed care and presents three particular ways it affects the
      profession of dentistry. The first issue is whether managed care is needed in
      dentistry; the second is the effects of managed care on treatment; and finally
      the dentist-patient relationship is examined. It is incumbent on dental students
      to be highly proficient in understanding and managing managed care because of the
      potential this system has for vast impact on patients, the profession, and one's
      practice.

PMID- 9929991
TI  - How the Japanese work.
AB  - The Japanese do not work harder or even use different approaches so much as they
      aim for a different result--one that balances process and results and extends the
      definition of quality beyond the product itself to include cost and convenience
      to the customer as well. Ten methods of the Japanese kaizen culture of work are
      presented with applications and contrasts to American dentistry.

PMID- 9929992
TI  - A clinician's guide to a woman's heart.
AB  - Contrary to the perception of most women that breast cancer is the leading cause
      of death in women, it is heart disease and stroke that claim the most lives of
      women older than 35 years in the United States. The prevalence of cardiovascular
      disease is likely to increase as more women--notably the "baby boomers"--enter
      the menopausal period, a time of increased cardiac vulnerability. Primary care
      physicians should be on the forefront in taking an inventory of risk factors in
      their female patients and in educating them about the reality of heart disease in
      their gender and about the risk factors that these patients can modify to
      decrease their risk. To aid in their efforts, this article provides an overview
      of those risk factors that are modifiable, such as weight reduction, exercise,
      and smoking cessation. It also offers an evaluation of the benefit and nonbenefit
      of vitamin and herbal supplements in reduction of cardiac events.

PMID- 9929993
TI  - Smoking in women.
AB  - Smoking has numerous increased health risks for women, including the risks for
      cancer, cardiovascular disease, chronic obstructive pulmonary disease, gastric
      and duodenal ulcers, reduced fertility, ovulatory dysfunction, ectopic pregnancy,
      spontaneous abortion, sudden infant death, and earlier menopause. Such health
      risks, smoking cessation therapy, and unique obstacles to smoking cessation in
      women are the focus of this article.

PMID- 9929995
TI  - Nongynecologic healthcare screening in women.
AB  - The primary care physician is bombarded with recommendations regarding health
      screening and preventive services. Often, these recommendations and guidelines
      are in conflict. This article will not settle these debates; however, it will
      provide an overview of recommendations for screening in nongynecologic areas and
      a framework on how to evaluate conflicting recommendations to give reasonable
      guidance to patients.

PMID- 9929994
TI  - Domestic violence: a primer for the primary care physician.
AB  - Domestic violence is a serious, complex, public health problem, which is more
      common than many physicians realize. Although certain characteristics may be
      associated with the victim and perpetrator, they have limited value in
      identification or prediction of partner violence. Any woman may be a victim and
      any man, a perpetrator; therefore, universal screening for partner abuse is
      encouraged. The medical and psychological consequences of domestic violence are
      often of tragic proportion, for both the woman and her children. Unfortunately,
      unless asked directly and in a supportive fashion, many women will remain silent
      and continue to be victimized.

PMID- 9929996
TI  - [Tularemia].

PMID- 9929997
TI  - [Preliminary report of an epidemic tularemia outbreak in Valladolid].
AB  - We make here a preliminary report of the first 65 cases of tularemia diagnosed at
      our hospital pertaining to an epidemic outbreak occurred in the area served by
      the hospital. Diagnosis was made by the presence of a consistent clinical picture
      and the following laboratory criteria: antibody titre to. Francisella tularensis
      (tube agglutination) higher than or equal to 1/160, seroconversion or recovery of
      the microorganism from biological material. The mean age of our patients was 53.8
      +/- 13.5 years and female sex predominated (45 women). Fever, lymph node
      enlargement, cutaneous ulcers, asthenia, and weight loss were the most common
      symptoms. The presentation clinical forms included: ulceroganglionar (69%),
      typhoidal (14%), ganglionar (12.5%), pneumonic (1.5%), oculoganglionar (1.5%) and
      atypical (1.5%). The analytical data did not show significant changes with the
      exception of erythrocyte sedimentation rate. Streptomycin was the antibiotic of
      choice, followed by ciprofloxacin and gentamicin. The failure rate was 22%, and
      ciprofloxacin was used for retreatment in twelve occasions and ofloxacin in 1
      occasion with a good response. Tularemia is an infective disease which can become
      endemic in Spain and that should be considered by clinicians, particularly when
      unilateral enlarged lymph nodes, prolonged febrile syndromes, pharyngitis with
      negative culture, poor response to beta-lactams and atypical pneumonia are
      present.

PMID- 9929998
TI  - [Tularemia: report of 16 cases in the Castilla-Leon community].
AB  - OBJECTIVE: To report the clinico-epidemiological characteristics of 16 patients
      with the diagnosis of tularemia. METHOD: Retrospective review of clinical records
      of patients admitted to the hospital or examined at health centers in Vizcaya,
      with clinical course and epidemiology consistent with tularemia, from January to
      March 1998. CASE DEFINITION: Patient with suggestive clinical course and
      epidemiology (exposure to hares coming from the epizootic area) and positive
      serology (antibodies to Francisella tularensis > 1/160 in convalescent phase
      serum). RESULTS: Sixteen patients (8 males, 8 females) with a mean age of 53
      years. The incubation period ranged from 1 and 8 days (mean: 5). Nine patients
      had the ulceroganglionar form, two the pharyngeal form, one the oculoganglionar
      form and one the typhoidal form. In three patients only cutaneous lesion or
      lesions were observed. The antibiotic treatment administered included
      streptomycin for five patients, tobramycin for 2 patients, and ciprofloxacin,
      azithromycin and amoxicillin (plus doxycycline) for other three patients. Three
      patients received initially antitermic drugs (with poor response) and later two
      of them, doxycycline. The administered antibiotic in the remaining three patients
      was unknown. The clinical course was satisfactory in all of them and so far no
      relapses have been detected. CONCLUSIONS: The ulceroglandular form, as it appears
      in literature, was the most common form in this series of patients with
      tularemia. Neither severe diseases nor complications were observed. Although
      streptomycin is considered the drug of choice, other antibiotics are likely
      equally effective, at least for the non complicated forms of the disease.

PMID- 9929999
TI  - [Predictive variables of early hospital readmission in cardiac failure].
AB  - BACKGROUND: Heart failure (HF) is one of the diagnosis leading to a high number
      of readmissions in our hospitals. There is some controversy about the role played
      by two groups of variables on the risk or readmissions: patient-dependent
      variables, such as clinical severity, and the characteristics of medical care
      during the previous admission, in terms of care quality. METHODS:  STUDY
      POPULATION: admissions due to HF with home discharge. DESIGN: case-control study.
      CASES: episodes followed by emergent admission within 30 days because of related
      diagnosis ("early readmission") (n = 51). CONTROLS: random sample of episodes not
      followed by an early readmission (n = 51). Information collected: review of
      clinical records. Groups of predictive variables studied: demographics, clinical
      severity, clinical parameters prognostic of HF and characteristics of medical
      care. Bivariate and multivariate statistical analysis: logistic regression (LR).
      RESULTS: LR analysis detected only one variable predicting early readmission, the
      ischemic etiology. Odds ratio = 4.78 (95% CI: 1.44; 15.88). There were no
      differences between the study groups regarding age, sex, clinical instability at
      discharge, hospital stay length, severity (APACHE III and other evaluation
      methods) and other prognostic parameters of HF (ejection fraction, functional
      degree, cardiomegaly, concurrent diabetes, valvular disease, atrial fibrillation,
      hyponatremia, and use of anti-arrhythmic drugs). CONCLUSIONS: The risk for an
      early readmission is mainly explained by the clinical variables of patients,
      basically ischemic etiology, and not by the characteristics of medical care:
      clinical instability at discharge or hospital stay length.

PMID- 9930000
TI  - [Seroepidemiology of Bartonella henselae infection in a risk group].
AB  - BACKGROUND: Bartonella henselae infections are closely related to a number of
      clinical conditions of growing interest in our environment. As cats are the
      reservoir, and their bites and scratches are the main transmission mechanism, we
      attempted to study the seroepidemiology of the infection caused by this
      microorganism in a risk group of patients (cat owners) and a control group (blood
      donors). PATIENTS AND METHODS: October 1977. Measurement of antibody titres to B.
      henselae at different dilutions (breakpoint > or = 1:64) by indirect
      immunofluorescence (IFI) in 83 cat owners and 85 blood donors. Also, an
      epidemiologic investigation was carried out (age, sex, alcohol, intake, common
      cat exposure, cat bite or cat scratch, number and age of cats, bite or presence
      of fleas, use of repellents, clinical picture consistent with cat scratch disease
      [CSD]). RESULTS: Twenty-four cat owners (28.9%) and five blood donors (5.9%) had
      titres > or = 1:64 (OR: 6.51; 95% CI: 2.32 to 22.9). Also, the logistic
      regression analysis showed an association with daily alcohol intake and the
      previous antecedent of lymph node enlargement of unknown origin among cat owners.
      CONCLUSIONS: A high prevalence of antibodies to B. henselae was demonstrate among
      cat owners.

PMID- 9930001
TI  - [Impact of biomedical publications on the incorporation of new therapeutic
      attitudes in cardiovascular pathology].
AB  - OBJECTIVE: To evaluate the application degree of results from three clinical
      trials on cardiovascular pathology in clinical practice: SOLVD trial (in patients
      with congestive heart failure), SAVE trial (in patients with acute myocardial
      infarction) and SPINAF trial (in patients with chronic atrial fibrillation).
      DESIGN: Retrospective cross-sectional study performed in the first six months in
      1990 and 1992 (SOLVD trial) and in the first six months in 1991 and 1993 (SAVE
      trial) admitted to the Consorci Hospitalari del Parc Tauli, and a cross-sectional
      study in a single randomized sample of all patients with the discharge diagnosis
      of atrial fibrillation at Hospital Vall d'Hebron during 1994. An absolute
      increase of 23% and 19% in the prescription of ACEI agents was observed for
      patients with heart failure and myocardial infarction, respectively. Forty-eight
      percent of patients with atrial fibrillation received antithrombotic therapy,
      which included aspirin and acenocoumarine for 51% and 49% of cases, respectively.

PMID- 9930002
TI  - [Malaria in the 21st century: clinical and therapeutic problems in imported
      malaria].
AB  - Imported malaria is an ever growing disease in our country because of the
      increase in travels to endemic tropical areas where this disease is endemic. Many
      patients, when they come to our hospitals infected with P. falciparum have
      already received drugs for this disease, either as prophylaxis or treatment, as
      it occurred in the cases reported here in the years 1995 and 1997, all of the
      spanish individuals who had travelled to or lived in African countries. To remark
      from our data the relevance of resistance to prophylactic and therapeutical
      agents in wide geographical areas, the frequent misuse of antimalarial drugs and
      complications that can emerge with the standard treatment for malaria. It all
      leads to the development of new therapeutic approaches for this potentially fatal
      infection. Based on the clinical efficiency in cases of politreated malaria
      cases, as well as for its safety in patients to whom first choice drugs cannot be
      administered (such as quinine), we stress the new therapy made up with the
      association atovaquone-proguanil.

PMID- 9930003
TI  - [Autoimmune thyroid pathology in recently diagnosed diabetes mellitus type 1].
AB  - OBJECTIVE: To analyze the prevalence of autoimmune thyroid disease among adult
      patients with recently diagnosed diabetes mellitus type I and its possible
      correlation with beta-cell autoimmunity markers (ICA, GAD, and IA 2) and with the
      presentation characteristics of diabetes mellitus. PATIENTS AND METHODS: A total
      of 100 patients diagnosed from 1992 to 1996 were included and anti-thyroid
      antibodies (Ac), anti-thyroglobulin (aTG) and antiperoxidase (aTPO) were
      measured. A comparison followed of the clinical characteristics, biochemical
      markers, and beta-cell immunity markers between the group of patients with
      positive and negative antibody determinations. Differences between groups were
      compared by the Student "t" test and non-parametric tests were used for cases not
      fulfilling the application conditions. RESULTS: Among the 100 patients, 25 had
      Ac+, two with previously known thyroid pathology and eight diagnosed at that
      moment. The group with Ac+ was characterized by a predominance of females (68% vs
      32%; p = 0.001), lower bicarbonate levels (18.6 +/- 6.1 vs 21.3 +/- 6.4; p =
      0.026) and higher requirements for insulin at discharge (0.77 +/- 0.22 vs 0.59 +/
      0.25 IU/kg; p = 0.002). Among patients in the Ac+ group, patients with thyroid
      pathology were characterized by a higher prevalence of females (90% vs 53.3%; p =
      0.05) and a higher percentage of individuals with high anti-TPO titres (80% vs
      33.3% higher than 400 IU/ml; p = 0.02). ICAs (66.6% vs 26.6% higher than 40 U
      JDF; p = 0.05) and IA2 (44.4% vs 0% higher than 12 IU/ml, p = 0.01). CONCLUSIONS:
      There is a high prevalence of thyroid pathology prevalence among our adult
      population with recently diagnosed DMI. Patients with thyroid autoimmunity have
      higher antibody titres to beta-cell and a somewhat more severe clinical
      presentation form. Prospective studies are required to determine the long term
      relevance of these differences.

PMID- 9930004
TI  - [Hypertransaminemia and methotrexate: not always a toxic effect?].
AB  - Serial measurement of liver enzymes is useful to detect liver toxicity due to
      methotrexate in patients with rheumatoid arthritis or other rheumatic diseases.
      We have reviewed retrospectively 141 adult patients treated with methotrexate
      from 1988 to 1991. The more common diagnoses included rheumatoid arthritis (120
      cases) and psoriatic arthritis (12 cases). In periodic studies carried our every
      2-3 months, a transient increase in transaminase values associated with
      methotrexate in 13 patients (9.2%) was observed. Two patients developed a viral
      infection during therapy, one due to cytomegalovirus and the other due to the
      Epstein-Barr virus. Both patients had a favorable outcome once methotrexate was
      withdrawn.

PMID- 9930005
TI  - [Hepatopulmonary syndrome].

PMID- 9930006
TI  - [Risk factors in mild cranio-encephalic trauma].

PMID- 9930007
TI  - [Young woman with upper right lobe condensation].

PMID- 9930008
TI  - [Female cattle farmer with grouped follicular pustular lesions].

PMID- 9930009
TI  - [Pigmented lesion on the big toe].

PMID- 9930010
TI  - [Arthromyalgias and pulmonary nodules].

PMID- 9930011
TI  - [Prophylaxis for infective endocarditis].

PMID- 9930012
TI  - [Tularemia outbreak in Castilla-Leon: report of the first case diagnosed in the
      Valencia Community].

PMID- 9930013
TI  - [Evolution of etiology of nosocomial infection in intensive care].

PMID- 9930014
TI  - [Pseudo-neoplastic appearance of cytomegalic infection in the digestive tract].

PMID- 9930015
TI  - [Vibrio cholerae non 01 sepsis in a healthy patient: review of reported cases in
      Spain].

PMID- 9930017
TI  - [Hypertensive crisis and vesical mass].

PMID- 9930016
TI  - [SIADH and treatment with selective inhibitors of serotonin recapture].

PMID- 9930018
TI  - [Genetically modified organisms (GMO): toxicological aspects].
AB  - The genetically modified organisms (GMO) are one of the major public concerns
      partially due to the activity of the non-governmental organizations which believe
      that public opinion must be duly informed on what leaves the laboratories and
      enters the environment or is proposed as food. This article discusses some major
      toxicological and nutritional aspects of GMO designed as food for humans. The
      range of current use of GMOs, potential hazards for humans, safety assessment,
      allergenic concerns, and some aspects of the use of marker genes are discussed in
      regard to human safety. The need for relevant regulations is stressed.

PMID- 9930019
TI  - [The role of cell proliferation in carcinogenesis].
AB  - Cell proliferation is regulated by the cell cycle which is controlled by a number
      of cyclin-dependent kinases (CDKs). The functions of CDKs are critical for cell
      cycle and are required to traverse checkpoints. A network of inhibitors (CKI) of
      the cyclin-dependent kinases provide the important function of regulating the
      activity of the cyclin complexes. Deregulation of these results in either
      uncontrolled proliferation or cell death (apoptosis). Cell proliferation is an
      important factor in the development of carcinogenesis induced by genotoxic as
      well as nongenotoxic carcinogens. It is an integral part of the process of
      converting DNA adducts to mutations, it also decreases the time that is available
      for DNA repair and is required to clonal expansion of initiated cell populations.
      Moreover, cell proliferation increases the number of initiated cells by blocking
      cell death (apoptosis) and pertrubing checkpoints in the cell cycle. Two major
      mechanisms of induction of cell proliferation (regenerative and mitogens
      stimulated) were discussed in relation to their potential roles in the
      carcinogenicity.

PMID- 9930020
TI  - [Determination of the mutagenic activity of cyclohexane extract of atmospheric
      air dust and polycyclic aromatic hydrocarbons on various strains of Drosophila
      melanogaster].
AB  - Using the test of somatic mutation and recombination (SMART) the mutagenic
      activity was studied in two cross-breed Drosophila melanogaster strains. In the
      strain mwh x ORR;flr3/TM3, Ser the concentration of cytochrome P-450-associated
      enzymes necessary faetivation of many promutagens, e.g. benzo(a)pyrene is many
      times higher. Cyclohexane extracts of atmospheric dust and certain polycyclic
      aromatic hydrocarbons were studied separately or in combination of two different
      ones. The study showed that: reliable results of the determinations of the
      mutagenicity of various polycyclic aromatic hydrocarbons were obtained only with
      the strain with high activity of enzymes activating promutagens, that is strain
      OR;flt3/TM3,Ser; mixtures of promutagens in concentrations of several mmols can
      show lower mutagenicity than the most mutagenic component of the mixture given
      separately. This could be the cause of stopped rise of the dose-response curve;
      an overwhelming majority of mutations in studies of tar substances is not due to
      the action of strongly acting promutagens among the polycyclic aromatic
      hydrocarbons studied here, including BaP.

PMID- 9930021
TI  - Induction of dominant lethal mutations after exposure of male mice to
      cyclophosphamide.

PMID- 9930022
TI  - The level of endotoxin contamination in biopreparations.
AB  - Bacterial endotoxins as contamination of biopreparations have been estimated by
      chromogenic LAL test. Study on some compounds (aluminium hydroxide, formaldehyde
      and merthiolate) being components of vaccines showed no effect on the result of
      LAL test. The level of endotoxins in virus vaccines with the limits defined in
      producers certificate was adequate, the level of endotoxin was also low in virus
      vaccines of undefined requirements. The concentration of endotoxin in bacterial
      vaccines was differentiated. Considering the results of our experiments, as well
      as the fact, that the requirements for endotoxin contamination of bacterial
      vaccines are not available it seems necessary to establish the limits for these
      group of biopreparations.

PMID- 9930023
TI  - [Sensitivity of Pseudomonas sp. strain isolated from distilled water to
      disinfectants].
AB  - The aim of the study was to compare Pseudomonas sp. strain isolated from
      distilled water and grown on the sterile filtrate from this water with the
      referent strain of Pseudomonas aeruginosa NCTC 6749 grown under the standard
      conditions, with the respect to their sensitivity to eight common disinfectants.
      Partly modified EN 1040 method was applied. The reduction factor (RF) for at
      least five concentrations of each of the products were determined. The linear
      relationship between concentration of the disinfectants and RF was established in
      a graphic form. Sensitivity of the strains was compared at the RF = 4. The WS
      strain was found to be more sensitivity than the referent strain to the
      disinfectants. The ratio concentrations of the solutions that were effective
      during 15 minutes against both the strains were; 1.3 for ethyl alcohol; 2.1 for
      glutaraldehyde; 1.7 for formalin; 1.85 for phenol. In the case of chloramine-T,
      the sodium salt of dichloroisocyanuric acid, and peracetic acid the ratios of
      concentrations were 156.0; 96.5 and 21.5 respectively. They indicate much higher
      sensitivity of the strain isolated from distilled water to these chemicals.

PMID- 9930024
TI  - [Changes in rats liver in late period of intoxication with chlorphenvinphos in a
      single dose].
AB  - The present investigation was undertaken to study the effect of chlorphenvinphos
      on the activity of liver enzymes in acute poisoning with this compound. The
      investigation was carried out on male Wistar rats. The animals received oil-
      control group and oil solution of chlorphenvinphos in dose 0.5 or 0.1 LD50--the
      examined group, intragastrically. Material for examination was collected in the
      48 h after intoxication. Activity of GOT and GPT in a serum, cytosolic and
      mitochondrial fractions of liver; BGR and AcP in a serum and lysosomal fraction
      of liver, ChE in a serum and concentration of lactate in the cytosolic fraction
      of liver were assayed. It can be concluded that in the 48 h after intoxication
      with chlorphenvinphos, activity of ChE was normalized in the case of lower dose
      and has such tendency in the case of higher dose. The changes of other assayed
      parameters in the serum and liver homogenate indicates that in this period of
      study, the liver is in point of no return.

PMID- 9930025
TI  - [Effect of nitrates and nitrites on small intestine].
AB  - Toxic effects of nitrates and nitrites on absorptive and secretive functions of
      intestinal mucosa were described. The effect of nitrates and nitrites on
      maturation, differentiation and programmed cell death (apoptosis) in intestinal
      crypts was also discussed. Selected immunological functions of small intestine in
      nitrate- or nitrite-treated organism were evaluated.

PMID- 9930026
TI  - [Monitoring of pesticides residues in food in Poland].
AB  - In this paper, the results of monitoring of pesticide residues in food products
      are reported for the 3 years period 1995-1997. The monitoring included analysis
      of organochlorine compounds (DDT and its metabolites--DDD and DDE, HCH isomers
      alpha, beta and gamma, HCB and PCBs), pyrethroids and dithiocarbamates in variety
      of food products such as: milk and milk products, food for infants and children,
      fish products, potatoes, domestic fruit and vegetables, citrus and exotic fruits,
      which were taken from the market. The samples were collected from 15 regions of
      Poland. Mean values of sigma DDT and sigma HCH in food products of animal origin,
      including children foods, were much lower comparing with those, reported in
      previous years. Only few samples analyzed had violative residues exceeding
      Maximum Residue Limits (MRLs) for these compounds. In none of food samples of
      plant origin, organochlorine compounds residues exceed Polish tolerances. The
      residues of synthetic pyrethroids were detected in none of tested samples of
      potatoes. Mean concentrations of dithiocarbamate pesticides in fruit and
      vegetables were higher than observed at the beginning of 1990s. In five samples
      of leaf and stem vegetables, the detected levels of dithiocarbamates exceed or
      were equal to MRLs.

PMID- 9930028
TI  - [Occurrence and evaluation of a law frequency noise in residential buildings].
AB  - Low-frequency noise emitted into the environment by technical equipment in the
      residential buildings, including equipment of workshops for services or
      production near these buildings, was measured. In the spectrum of noise derived
      from installations and equipment in residential buildings and shops low frequency
      (20-125 Hz) sounds and infrasounds (below 20 Hz) were detected. Their sources
      were mainly pumps in hydrophors, lifts, cooling machinery, central heating, air
      conditioning and ventilating installations. The analysed noise was in a small
      degree only damped by partitions in buildings and penetrated more easily than
      higher-frequency noise, without exceeding usually the permitted levels. Noises
      with dominating low-frequency sounds are regarded by the inhabitants as
      troublesome and causing various adverse psychosomatic effects, such as pulsation
      feeling, somnolence, headaches, nausea etc. The present system of noise
      assessment leaves low-frequency noise aside and fails to protect sufficiently the
      inhabitants against this nuisance.

PMID- 9930027
TI  - [Fluorine in vegetables and potatoes from the market in Warsaw].
AB  - In 65 samples of vegetables: cabbages, carrots, beetroots, onions and potatoes,
      of whose consumption is the highest in Poland, fluorine content was determined.
      The samples were prepared according to AOAC method, and fluorine concentration
      was determined in the filtrate by the potentiometric method using a Fluoride-
      selective electrode--model 920A of Orion Research Inc. The recovery rate of
      fluorine was 95 +/- 5%. The average level of soluble fluorine ranged from 3.36
      mg/kg of dry weight of cabbage to 5.37 mg/kg of dry weight of onion and from 0.38
      mg/kg of fresh weight of cabbage to 1.02 mg/kg of fresh weight of potatoes. In
      over 50% of the investigated samples fluorine content exceeded 0.56 mg/kg of
      fresh weight, which is the upper limit value of fluorine content found in the
      vegetables from the areas ecologically clean.

PMID- 9930029
TI  - [Content of volatile in steam phenols in the main stream of cigarette smoke from
      selected brands of cigarettes].
AB  - Phenols constitute an important toxic component of the main stream (MS) of
      cigarette smoke. The content of volatile fraction of that group of compounds in
      MS depends on the tobacco type and conditions in which cigarettes are smoked, as
      well as on the filters applied. The purpose of the research was to determine the
      content of volatile in steam phenols in the MS of selected brands of cigarettes
      produces in Poland, as well as imported ones, and the assessment of the toxicity
      of doses of the phenols that smokers were exposed to. Cigarettes conditioned in
      constant humidity were smoked in standard conditions in the simulator of smoking,
      designed by the authors, while MS was absorbed in Zaitcev washers, filled with
      methanol. The absorbed phenols were distilled in steam and extracted with ethyl
      acetate. Then the phenols were separated by the method of overpressure thin-layer
      chromatography on DC Alufolien Polyamid 11F254 Merck chromatoplates, in the
      developing system chloroform-methanol 99:1 v/v, were induced with sodium
      diazofluoroborate, and after eultuion the separated phenol, and o-cresol were
      determined, as well as the non-separated mixture of p- and m-cresols, by the
      spectrophotometric method. The determined contents of phenols in MS were assessed
      regarding their toxicity applying the criteria of environmental exposure. When
      calculating the results, the efficiencies of the applied in the analytical
      procedures processes of absorption, distillation and extraction of the
      investigated phenols previously determined experimentally, were taken into
      consideration. The content of determined compounds in the brands of the
      cigarettes examined was in the case of phenols, changing within the range from
      41.25 +/- 1.15 to 7.60 +/- 0.93 (the average of 20.31 +/- 9.61 micrograms per
      cigarette); in the case oo-cresol it was within the range from 28.16 +/- 0.95 to
      5.72 +/- 0.53 (the average of 11.56 +/- 6.7), while for the non-separated p- and
      m-cresols the range was from 21.12 +/- 0.5 to 7.31 +/- 0.45 (the average amounted
      to 11.48 +/- 4.98 micrograms per cigarette The conclusions of the study were the
      brands of cigarettes significantly influences the content of the phenols examined
      in the cigarette smoke the phenols determined coexist in the MS of examined
      cigarettes in similar proportions the doses of phenols inhaled by a smoker during
      a day with the MS of examined brands of cigarettes participate essentially in the
      toxicity of the cigarette smoke and smoking 20 cigarettes a day causes the
      smoker's organism to be exposed to incomparably larger doses of phenols than
      those from unpolluted atmospheric air.

PMID- 9930030
TI  - [Evaluation of food consumption and nutritional status of children at preschool
      and school age based on the literature in 1980-1995].
AB  - The study includes a survey of literature reports from the last 15 years on the
      consumption of food and nutritional status of preschool and school children. The
      nutritional status of preschool and school children suggested many shortcomings
      independent of social class and nutrition type (individual, mass nutrition).
      Generally, the nutrition of town children was better than that of rural children,
      and signs of deficiency of certain vitamins and mineral components were found in
      a lowe per cent of the former children. The food rations of the studied children
      contained too low consumption of milk and dairy products, vegetables and fruit,
      with high intake of fats, meat and its products, sugar and sweets. The daily food
      rations contained low amounts of calcium, vitamins A, B and C, with excess of
      phosphorus and fats. The nutrition of school children depended on year season,
      social class and education of parents. The most frequent faults included
      inappropriate timetable of meals, their poor quality, inadequate number and
      monotony. No such data could be obtained with respect to preschool children. The
      nutritional status of preschool and school children gives rise to objections,
      especially in the case of rural areas. There is a need to evolve and introduce a
      standardized study method for the assessment of nutrition and nutritional status
      of preschool and school children and continuous monitoring in this respect.

PMID- 9930031
TI  - Integration of vitamin A supplementation with immunization.

PMID- 9930032
TI  - Measurement of QT dispersion.

PMID- 9930033
TI  - Stamps in cardiology. Blood transfusion.

PMID- 9930034
TI  - Anatomic repair of double discordant hearts.

PMID- 9930035
TI  - Images in cardiology. Delayed appearance of coronary aneurysms in Kawasaki
      disease.

PMID- 9930036
TI  - Heart failure clinics.

PMID- 9930037
TI  - Heart failure clinics: a possible means of improving care.

PMID- 9930038
TI  - Nurse led, multidisciplinary intervention in chronic heart failure.

PMID- 9930039
TI  - Prevention of relapse in patients with congestive heart failure: the role of
      precipitating factors.
AB  - Relapse of congestive heart failure (CHF) frequently occurs and has serious
      consequences in terms of morbidity, mortality, and health care expenditure. Many
      studies have investigated the aetiological and prognostic factors of CHF, but
      there are only limited data on the role of precipitating factors that trigger
      relapse of CHF. Knowledge of potential precipitating factors may help to optimise
      treatment and provide guidance for patients with CHF. The literature was reviewed
      to identify factors that may influence haemodynamic homeostasis in CHF.
      Precipitating factors that may offer opportunities for preventing relapse of CHF
      were selected. Potential precipitating factors are discussed in relation to the
      pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled
      hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment
      compliance, and inappropriate medical treatment. Poor treatment compliance in
      particular is frequently encountered in patients with CHF. Furthermore, studies
      of medical treatment under everyday circumstances indicate that some aspects of
      the management of CHF can be improved. In conclusion, the identification of
      precipitating factors for relapse of CHF may strongly contribute to optimal
      treatment. Improvement of treatment compliance and optimalisation of medical
      treatment may offer important possibilities to clinicians to reduce the number of
      relapses in patients with CHF.

PMID- 9930040
TI  - Preventable causative factors leading to hospital admission with decompensated
      heart failure.
AB  - OBJECTIVE: To determine the distribution and importance of various factors,
      especially the preventable ones, that contribute to cardiac decompensation and
      subsequent hospital admission for heart failure. METHODS: During a one year
      period patients were prospectively recruited and evaluated during their hospital
      stay by means of a structured personal interview by trained medical staff and
      through clinical examination and laboratory investigation. SETTING: The
      cardiological department at a teaching affiliated general community hospital in
      Berlin, Germany. PATIENTS: Consecutive sample of 179 patients admitted to
      hospital with acute decompensation of pre-existing heart failure. MAIN OUTCOME
      MEASURES: Proportional distribution of causative factors leading to hospital
      admission for heart failure; relative importance of preventable factors; details
      of patient compliance with diet and medication, and knowledge about medication.
      RESULTS: Mean (SD) age was 75.4 (9.9) years. Potential causative factors for
      decompensated heart failure were identified in 85.5% of patients. Lack of
      adherence to the medical regimen was the most commonly identified factor and was
      regarded as the cause of the cardiac decompensation in 41.9% of cases. Non
      compliance with drugs was found in 23.5% of patients. Other factors related to
      hospital admission were coronary ischaemia (13.4%), cardiac arrhythmias (6.1%),
      uncontrolled hypertension (5.6%), and inadequate preadmission treatment (12.3%).
      In all, 54.2% of admissions could be regarded as preventable. CONCLUSIONS: Many
      hospital admissions for decompensation of chronic heart failure in patients at a
      district hospital in Berlin are preventable. Measures are necessary to improve
      this situation and evaluation of programmes that include patient education,
      patient follow up, and physician training is needed.

PMID- 9930041
TI  - Cost effective management programme for heart failure reduces hospitalisation.
AB  - OBJECTIVE: To study the effects of a management programme on hospitalisation and
      health care costs one year after admission for heart failure. DESIGN:
      Prospective, randomised trial. SETTING: University hospital with a primary
      catchment area of 250,000 inhabitants. PATIENTS: 190 patients (aged 65-84 years,
      52.3% men) hospitalised because of heart failure. INTERVENTION: Two types of
      patient management were compared. The intervention group received education on
      heart failure and self management, with follow up at an easy access, nurse
      directed outpatient clinic for one year after discharge. The control group was
      managed according to routine clinical practice. MAIN OUTCOME MEASURES: Time to
      readmission, days in hospital, and health care costs during one year. RESULTS:
      The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n =
      56) in the intervention group (NS). The mean time to readmission was longer in
      the intervention group than in the control group (141 (87) v 106 (101); p < 0.05)
      and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p =
      0.07). There was a trend towards a mean annual reduction in health care costs per
      patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with
      costs in the controls (US$3594 v 2294; p = 0.07). CONCLUSIONS: A management
      programme for patients with heart failure discharged after hospitalisation
      reduces health care costs and the need for readmission.

PMID- 9930042
TI  - Secondary prevention in coronary heart disease: a randomised trial of nurse led
      clinics in primary care.
AB  - OBJECTIVE: To evaluate whether nurse run clinics in general practice improve
      secondary prevention in patients with coronary heart disease. DESIGN: Randomised
      controlled trial. SETTING: A random sample of 19 general practices in northeast
      Scotland. PATIENTS: 1173 patients (685 men and 488 women) under 80 years with
      working diagnoses of coronary heart disease, but without terminal illness or
      dementia and not housebound. INTERVENTION: Nurse run clinics promoted medical and
      lifestyle aspects of secondary prevention and offered regular follow up. MAIN
      OUTCOME MEASURES: Components of secondary prevention assessed at baseline and one
      year were: aspirin use; blood pressure management; lipid management; physical
      activity; dietary fat; and smoking status. A cumulative score was generated by
      counting the number of appropriate components of secondary prevention for each
      patient. RESULTS: There were significant improvements in aspirin management (odds
      ratio 3.22, 95% confidence interval 2.15 to 4.80), blood pressure management
      (5.32, 3.01 to 9.41), lipid management (3.19, 2.39 to 4.26), physical activity
      (1.67, 1.23 to 2.26) and diet (1.47, 1.10 to 1.96). There was no effect on
      smoking cessation (0.78, 0.47 to 1.28). Of six possible components of secondary
      prevention, the baseline mean was 3.27. The adjusted mean improvement
      attributable to intervention was 0.55 of a component (0.44 to 0.67). Improvement
      was found regardless of practice baseline performance. CONCLUSIONS: Nurse run
      clinics proved practical to implement in general practice and effectively
      increased secondary prevention in coronary heart disease. Most patients gained at
      least one effective component of secondary prevention and, for them, future
      cardiovascular events and mortality could be reduced by up to a third.

PMID- 9930043
TI  - Measurement error as a source of QT dispersion: a computerised analysis.
AB  - OBJECTIVE: To establish a general method to estimate the measuring error in QT
      dispersion (QTD) determination, and to assess this error using a computer program
      for automated measurement of QTD. SUBJECTS: Measurements were done on 1220
      standard simultaneous 12 lead electrocardiograms. DESIGN: The computer program
      was validated against two observers on a random subset of 100 electrocardiograms.
      Simple laws of physics require that at least five of the six extremity leads have
      the same QT duration. This allows the direct assessment of the error in measuring
      QTD derived from five extremity leads (QTD5). It also enables ST-T amplitude
      dependent distributions of measurement error in determining QT duration to be
      established. These QT error distributions were then used to estimate the error in
      measuring QTD from all 12 leads (QTD12). MAIN OUTCOME MEASURES: Mean and standard
      deviation of error in measuring QTD duration, QTD5, and QTD12. RESULTS:
      Performance of the program was comparable to that of observers. Errors in
      measuring QT duration (measured QT minus reference QT) fell from a mean (SD) of
      6.9 (17.1) ms for ST-T amplitudes < 50 microV to -1.4 (6.3) ms for amplitudes >
      350 microV. Measurement errors of QTD5 and QTD12 were 20.4 (11.5) ms and 29.4
      (14.9) ms. CONCLUSIONS: The fact that no QTD can exist between five of the six
      extremity leads provides a means of estimating QTD measurement error. Measuring
      error of QT duration is dependent on ST-T amplitude. QTD measurement error is
      large compared with typical QTD values reported.

PMID- 9930044
TI  - Computerised measurements of QT dispersion in healthy subjects.
AB  - OBJECTIVE: To assess the stability and reproducibility of computerised QT
      dispersion (QTd) measurement in healthy subjects, as this is presently being
      incorporated into commercial electrocardiographic systems. METHODS: 70 healthy
      volunteers (mean (SD) age 38 (10) years, 35 men, 35 women) with a normal 12 lead
      electrocardiogram (ECG) were studied. From each subject, 70 ECG recordings were
      taken using the MAC VU ECG recorder (Marquette). In study A, 50 ECGs were
      recorded in each subject: 10 supine, 10 sitting, 10 standing, 10 holding breath
      in maximum inspiration, and 10 holding breath in maximum expiration. After a mean
      interval of 8 (3) days (range 7 to 23), 10 recordings in supine and 10 in the
      standing position were repeated in each subject (study B). On measurements made
      using a research version of the commercial software without manual modification,
      the reproducibility of QTd was assessed by coefficient of variance (CV) and
      relative error, and comparisons made with other ECG indices. RESULTS: (1) QTd
      measurements were stable and not influenced by changes in posture and respiratory
      cycle; (2) there was no difference in QTd measurements between men and women, or
      between age groups dichotomised at 35 years; (3) no correlation was found between
      QTd and heart rate or QT interval; (4) short term reproducibility of all QTd
      measurements (CV 15.6% to 43.8%) was worse than that of conventional ECG indices
      (CV 1.4% to 5.3%); (5) long term reproducibility of QTd measurements (relative
      error 27.4% to 31.0%) was also worse than that of conventional ECG indices
      (relative error 1.8% to 7.9%) (p < 0.0001); (6) the reproducibility of QTd
      measurements tended to increase when several serial recordings were averaged.
      CONCLUSIONS: Computerised measurements of global QTd and global QT-SD from 12
      lead ECG by the MAC VU/QT Guard system are not significantly altered by changes
      in posture and respiration. The reproducibility of all QTd measurements is
      inferior to that of conventional ECG indices in healthy subjects.

PMID- 9930045
TI  - Images in cardiology. Pacemaker induced torsades de pointes tachycardia.

PMID- 9930046
TI  - Prediction of the onset of atrial fibrillation after cardiac surgery using the
      monophasic action potential.
AB  - OBJECTIVE: To show that the monophasic action potential (MAP) recorded
      continuously from human epicardium may be used to predict the imminent onset of
      atrial fibrillation or flutter (AF) following surgery, thus allowing prophylactic
      treatment to be started. PATIENTS: 22 patients (14 male, 8 female; mean (SD) age
      64 (12) years) undergoing aortic valve replacement. SETTING: Tertiary referral
      centre. METHODS: Over a mean observation period of 8 (2.7) days (range 4 to 14),
      nine episodes of AF were seen in six patients. Before AF, specific and
      significant alterations of the MAP morphology were observed. In seven of nine
      episodes the MAP shortened (25 (4)% 60 minutes before AF), developed a triangular
      shape, and the plateau amplitude decreased from 5.3 (1.2) to 2 (0.2) mV. In the
      two remaining episodes the beat to beat variability of cycle length and MAP
      duration at 90% repolarisation (MAPd90) increased significantly from 24 (7) ms
      and 12 (8) ms (24 hours before AF) to 137 (27) ms and 56 (11) ms (30 minutes
      before AF) respectively. AF was successfully treated by the administration of
      sotalol in three cases and by a combination of verapamil and digoxin in a further
      four. Previously observed changes of MAPd90 and MAP morphology regressed after
      conversion to sinus rhythm. CONCLUSIONS: The continuous and intermediate term
      recording of the MAP from atrial epicardium appears to be a valid tool for
      detecting imminent AF after cardiac surgery with a high sensitivity (99%) and
      specificity (88%). Optimised antiarrhythmic treatment may thus be given
      selectively for prophylaxis.

PMID- 9930047
TI  - Role of orthotopic heart transplantation in the management of patients with
      recurrent ventricular tachyarrhythmias following myocardial infarction.
AB  - OBJECTIVE: To report the outcome of an intention to treat by heart
      transplantation strategy in two groups of patients after infarction, one with
      both left ventricular failure (LVF) and ventricular tachyarrhythmias (VTA) (group
      A) and the other with progressive LVF following antiarrhythmic surgery for VTA
      (group B). PATIENTS AND METHODS: Group A comprised 17 consecutive patients for
      whom transplantation was considered the best primary non-pharmacological
      treatment; group B comprised five consecutive patients assessed and planned for
      transplantation after antiarrhythmic surgery. RESULTS: In group A, eight patients
      underwent transplantation and all survived the first 30 day period. At median
      follow up of 55 months (range 11 to 109) seven of this subgroup were still alive.
      Five patients died of recurrent VTA before transplantation, despite circulatory
      support. In the face of uncontrollable VTA, four of these underwent "high risk"
      antiarrhythmic surgery while awaiting transplantation: three died of LVF within
      30 days and one was saved by heart transplantation two days after arrhythmia
      surgery. Mortality for the transplantation strategy in group A patients was 47%
      by intention to treat analysis. Quality of life in the eight actually
      transplanted, however, was good and only one died during median follow up of 56
      months. The five patients in group B were accepted for transplantation for
      progressive LVF at a median of 21 months (range 12 to 28) after antiarrhythmic
      surgery. One died of LVF before transplantation, 22 months after initial surgery;
      another died of high output LVF three days after transplantation. Thus mortality
      of the intended strategy was 40%. The three transplanted patients are alive and
      well at 8-86 months. CONCLUSIONS: Although the short and medium term outcome in
      category A or B patients who undergo transplantation is good, the overall success
      of the transplantation strategy in category A patients is limited by lack of
      donors in the short time frame in which they are required.

PMID- 9930048
TI  - Maintaining tricuspid valve competence in double discordance: a challenge for the
      paediatric cardiologist.
AB  - OBJECTIVES: To establish the prevalence of tricuspid valve abnormalities in
      children with a double discordant heart (or congenitally corrected transposition
      of the great arteries); to study the influence of the loading conditions induced
      by various surgical interventions on the right and left ventricle in patients
      with double discordance and an abnormal tricuspid valve; and to propose a
      rational surgical approach. METHODS: Case notes were reviewed of 141 consecutive
      patients admitted in the first year of life with various types of double
      discordance (intact ventricular septum (group 1), ventricular septal defect
      (group 2), ventricular septal defect and pulmonary obstruction (group 3)). A
      study group of 62 patients with an abnormal tricuspid valve was selected by cross
      sectional echocardiography. These were followed up through palliative and open
      heart procedures with grading of tricuspid regurgitation. RESULTS: Tricuspid
      valve abnormalities were more common in groups 1 and 2 (60% and 56%) than in
      group 3 (31%). Preoperative tricuspid regurgitation was more common in group 2
      (90%) than in groups 1 and 3 (38% and 36%). Ten patients in groups 1 and 2 died
      in the neonatal period with severe tricuspid regurgitation, associated with
      coarctation of the aorta in 60%. Eight patients in group 1 had no surgery and are
      doing well, with a competent tricuspid valve. Palliative procedures were
      undertaken in 28 patients: 14 had pulmonary artery banding, which resulted in a
      decrease in tricuspid regurgitation, 12 in group 2 by reducing the pulmonary
      blood flow and two in group 1 by changing the septal geometry; 14 in group 3 had
      an aortopulmonary shunt, which induced tricuspid regurgitation in two. Twenty
      patients are still alive after palliation, with stable tricuspid valve function.
      Repair of the tricuspid valve was unsuccessful in the three patients who
      underwent conventional surgery, leaving the right ventricle facing the systemic
      circulation. In two patients with a competent but abnormal tricuspid valve,
      conventional surgery induced severe tricuspid regurgitation. Of the 15 patients
      who underwent conventional surgery, only 10 survived (mortality 33%): eight with
      a tricuspid valve prosthesis and two with severe residual tricuspid
      regurgitation. However, tricuspid regurgitation decreased after anatomical
      correction (nine patients), restoring a systemic left ventricle and a
      subpulmonary right ventricle, even when the tricuspid valve was not repaired
      (five patients). Eight patients are doing well after anatomical correction
      (mortality 11%). CONCLUSIONS: Tricuspid valve function in double discordance with
      an abnormal tricuspid valve depends on the loading conditions of both ventricles
      and on the septal geometry. Interventions that increase right ventricular volume
      or decrease left ventricular pressure are likely to induce tricuspid
      regurgitation, while those that decrease right ventricular volume or increase
      left ventricular pressure are likely to improve tricuspid valve function. Repair
      of the tricuspid valve always failed when the right ventricle was left in a
      systemic position and always succeeded when the right ventricle was placed in a
      subpulmonary position. These results should be taken in to account when dealing
      with patients with double discordance and an abnormal tricuspid valve.

PMID- 9930049
TI  - Pulmonary function in children with atrial septal defect before and after heart
      surgery.
AB  - OBJECTIVE: To test the effect of heart disease and heart surgery on lung
      function. DESIGN: A pulmonary function study of children undergoing surgery for
      atrial septal defect (ASD). SETTINGS: University hospital. PATIENTS: 26 children
      tested before surgery (at mean (SD) age 11.8 (3.8) years) and 24 patients tested
      1.8 (0.2) years after surgical correction. METHODS: Lung volumes, lung
      elasticity, and airway patency indices were measured using standard techniques.
      RESULTS: Before surgery: pulmonary function test abnormalities were found in 18
      of the 26 patients. Stiff lung was found in 12, lung hyperinflation in five, and
      indices of decreased airway patency in four. Total lung capacity decreased in
      only two patients. After surgery: pulmonary function test abnormalities were
      found in 12 of the 24 patients (informed consent not given for two patients).
      Stiff lung was detected in nine and indices of peripheral airway obstruction in
      four. Mean values of specific airway conductance and peak expiratory flow were
      all normal. Lung hyperinflation was found only in one of 24 patients. No
      correlation between perioperative events and pulmonary function test data was
      found. CONCLUSIONS: Pulmonary function test abnormalities persist in half the
      patients almost two years after surgery for ASD. A decrease in the total
      frequency of pulmonary function test abnormalities (in 19% of the patients), with
      a decrease in stiff lung in 8% and lung hyperinflation in 15%, was not
      significant. Impairment of lung function related to ASD is associated with the
      disease itself rather than the surgical procedure.

PMID- 9930050
TI  - Triggers of daily life ischaemia.
AB  - OBJECTIVE: To determine the usual triggers of silent and symptomatic ischaemia.
      DESIGN: Patients wore an ambulatory recorder for 48 hours. The device emitted a
      tone on detection of ischaemia and patients noted activities, feelings, and
      symptoms so that ischaemia could be attributed to one of four triggers: physical
      stress, mental stress, combined physical/mental stress, or no stressor. SETTING:
      Home environment. PATIENTS: Patients (n = 38) with stable coronary disease,
      positive exercise electrocardiography, and ischaemic episodes on ambulatory
      electrocardiography. MAIN OUTCOME MEASURE: Matching ischaemic episodes with
      perceived triggers. RESULTS: Altogether 257 ischaemic episodes (53% silent) were
      documented. Triggers were: physical stress, 56%; mental stress, 5%; combined
      physical/mental stress, 8%; no identifiable trigger, 31%. Episodes associated
      with mental or no stress were more often silent (69% and 75%, respectively) than
      those associated with physical stress (45%, p < 0.01), while combined
      physical/mental stress episodes were usually symptomatic (10% silent, p < 0.01 v
      other stressors). Although physical stress was less commonly a trigger of silent
      ischaemia than angina (47% v 65%, p < 0.01), it was still the predominant trigger
      of silent ischaemia. There was no identifiable trigger in 45% of silent and only
      17% of anginal episodes (p < 0.01). Only nine silent episodes involved mental
      stress alone as a trigger. CONCLUSIONS: Daily life ischaemia is usually triggered
      by physical activity. Mental stress alone is an uncommon trigger of either silent
      or symptomatic ischaemia, while combined physical/mental stress is a significant
      but minor trigger of angina. Patients can identify a trigger in 83% of anginal
      episodes, compared with only half of silent ischaemic episodes.

PMID- 9930051
TI  - Coronary flow reserve in the contralateral artery increases after successful
      coronary angioplasty in patients with spontaneously visible collateral vessels.
AB  - OBJECTIVE: To test the hypothesis that coronary flow reserve could increase in
      the angiographically normal contralateral artery after successful coronary
      angioplasty of an ipsilateral coronary artery. DESIGN: Coronary flow reserve was
      estimated using a Doppler flow guide wire, by giving intracoronary adenosine in
      the contralateral artery, before and 15 minutes after the end of angioplasty.
      SETTING: Tertiary referral centre. PATIENTS: 31 patients, mean (SD) age 56 (11)
      years, with stable angina and single vessel disease, undergoing angioplasty of
      the right coronary or the left anterior descending artery. RESULTS: In the
      contralateral artery baseline average peak velocity was 21 (9) cm/s before
      angioplasty and decreased to 12 (6) cm/s after (p < 0.005), while hyperaemic
      average peak velocity was 47 (19) cm/s before and decreased to 34 (15) cm/s after
      (p < 0.005). However, coronary flow reserve in the contralateral artery was 2.4
      (0.7) before angioplasty and increased to 2.9 (0.6) after (p < 0.05). The
      contralateral coronary flow reserve after angioplasty increased by 0.8 (0.4) in
      11 patients with visible collaterals before angioplasty and by 0.3 (0.6) in the
      remaining patients without visible collaterals (p < 0.05). Blood pressure and
      heart rate were unchanged after the procedure. CONCLUSIONS: Coronary flow reserve
      in an angiographically normal contralateral artery increases after successful
      coronary angioplasty of the ipsilateral artery in patients with spontaneously
      visible collateral vessels before the procedure.

PMID- 9930053
TI  - Impact of stenting on coronary angioplasty procedures.
AB  - OBJECTIVE: To compare patient selection and outcome of coronary angioplasty
      procedures before and after the widespread availability and use of stents.
      SUBJECTS AND METHODS: Group 1 consisted of 252 consecutive patients and group 2
      comprised 389 patients who underwent angioplasty between April 1993 and March
      1994, and April 1995 and March 1996, respectively, in a tertiary cardiothoracic
      centre. Clinical variables were collected before the procedures. Endpoints
      included in-hospital death, the need for repeat coronary angiography, repeat
      angioplasty, and coronary artery bypass surgery. Lesions were classified under
      American Heart Association/American College of Cardiology criteria in 100
      randomly selected patients from each group. RESULTS: 311 and 482 angioplasty
      procedures were performed in patients from groups 1 and 2, respectively. One or
      more stents were deployed in nine (4%) and 179 (46%, p < 0.01) patients,
      respectively. The success rate was higher in group 2 than in group 1 patients
      (483/523 (92%) v 274/372 (88%), respectively, p < 0.05). There were significantly
      more single vessel angioplasty procedures (198/252 (79%) v 272/389 (70%), p <
      0.05), type A lesions (30/116 (26%) v 19/130 (15%), p < 0.05), patients with
      stable angina (220/252 (87%) v 311/389 (80%), p < 0.05), and fewer acute
      myocardial infarction patients (1/252 (0%) v 12/389 (3%), p < 0.05) treated in
      group 1 than in group 2, respectively. Similar numbers of angioplasty were
      performed in the left anterior descending, left circumflex, and right coronary
      arteries. There were no significant differences in the in-hospital mortality or
      the need for repeat coronary angiography, angioplasty, or bypass surgery at 24
      hours or six months after the initial procedure. CONCLUSION: Patients undergoing
      angioplasty in the stenting era had features associated with an increased risk of
      complication. Despite this, the primary success rate was higher, and the
      complication rate and the need for subsequent revascularisation were similar in
      the two groups, supporting the widely held clinical impression that stenting has
      made a valuable impact on the practice of angioplasty.

PMID- 9930052
TI  - Intracoronary Multi-link stents: experience in 218 patients using aspirin alone.
AB  - OBJECTIVES: To assess procedural outcome, complications, and clinical follow up
      in 218 patients who underwent treatment with 297 Multi-link (Guidant) stents
      implanted without the use of intravascular ultrasound (IVUS) or quantitative
      coronary angiography (QCA), and using aspirin alone as antiplatelet therapy.
      METHODS: The case records and angiograms were reviewed and the patients were
      contacted by telephone to determine their symptoms and any adverse events at
      follow up. Data were analysed using Fisher's exact test. RESULTS: Of the 218
      patients included in the study, 45 had multivessel intracoronary intervention,
      and 55 had unstable angina. The mean (SD) length of hospital stay following the
      procedure was 2.0 (2.1) days. There were two early deaths at less than 30 days,
      and two deaths during follow up at more than 100 days. Ten patients suffered
      complications during the first 30 days: four had subacute stent thrombosis, of
      whom two died and two were treated successfully with coronary artery bypass
      grafting; five had a non-Q wave myocardial infarction; and one had a femoral
      false aneurysm. Patient outcome was analysed according to stent diameter (3.0 mm
      or less, or 3.5 mm or more) and by angina status (stable or unstable). In
      patients in whom at least one stent was 3.0 mm diameter, four of 86 patients
      suffered acute stent occlusion, whereas in the 132 patients in whom all stents
      were at least 3.5 mm diameter there were no cases of stent occlusion (p = 0.02).
      In the unstable angina group two of 55 patients suffered acute stent occlusion
      compared to two of 163 patients in the stable angina group (NS). In patients with
      unstable angina and at least one stent of 3.0 mm diameter, the acute occlusion
      rate was 7.1% (two of 28 patients). Three of the four patients with stent
      occlusion had undergone complex procedures. Twenty eight patients were restudied
      for recurrent symptoms during the follow up period. Of these, eight patients had
      restenosis within their stent. In seven of these patients the stent size was 3.0
      mm diameter, and in the remaining patient the stent size was 4.0 mm diameter.
      Three of the 28 patients restudied had developed new disease remote from the
      stented site, and 17 had patent stents and no significant other coronary lesion.
      CONCLUSIONS: This study suggests that coronary intervention using the Multi-link
      stent is safe and effective using aspirin alone, without IVUS or QCA, when stent
      diameter is greater than 3.0 mm. All cases of stent occlusion in this series
      occurred in patients in whom at least one stent was 3.0 mm diameter, with stent
      occlusion being higher in patients with unstable angina compared to those with
      stable angina. Additional antiplatelet therapy may be beneficial in those
      patients in whom Multi-link stent diameter is less than 3.5 mm, particularly in
      those with unstable angina, but is not necessary for patients receiving Multi
      link stents of 3.5 mm diameter or greater.

PMID- 9930054
TI  - Images in cardiology. Dual atrial pathology as an incidental finding on thoracic
      computed tomography and echocardiography.

PMID- 9930055
TI  - Intravascular stents: a new technique for tissue processing for histology,
      immunohistochemistry, and transmission electron microscopy.
AB  - BACKGROUND: Study of the vascular response to stent implantation has been
      hampered by difficulties in sectioning metal and tissue without distortion of the
      tissue stent interface. The metal is often removed before histochemical
      processing, causing a loss of arterial architecture. Histological and
      immunohistochemical sections should be 5 microns with an intact tissue stent
      interface. OBJECTIVES: To identify the most suitable cutting and grinding
      equipment, embedding resin, and slides for producing thin sections of stented
      arteries with the stent wires in situ for histological, immunohistochemical, and
      transmission electron microscopic (TEM) analyses. METHODS: 20 balloon stainless
      steel stents were implanted in the coronary arteries of 10 pigs. Twenty eight
      days later the stented arterial segments were excised, formalin fixed, embedded
      in five different resins (Epon 812, LR white, T9100, T8100, and JB4), and
      sectioned with two different high speed saws and a grinder for histological,
      immunohistochemical, and TEM analyses. Five stented human arteries were obtained
      at necropsy and processed using the best of the reported methods. RESULTS: The
      Isomet precision saw and grinder/polisher unit reliably produced 5 microns
      sections with most embedding resins; minimum section thickness with the
      horizontal saw was 400 microns. Resin T8100, a glycol methacrylate, enabled
      satisfactory sectioning, grinding, and histological (toluidine blue, haematoxylin
      and eosin, and trichromatic and polychromatic stains) and immunohistochemical
      analyses (alpha smooth muscle actin, von Willebrand factor, vimentin,
      proliferating cell nuclear antigen, and CD68 (mac 387)). T9100 and T8100 embedded
      stented sections were suitable for ultrastructural examination with TEM. Stented
      human arterial sections showed preserved arterial architecture with the struts in
      situ. CONCLUSION: This study identified the optimal methods for embedding,
      sawing, grinding, and slide mounting of stented arteries to achieve 5 microns
      sections with an intact tissue metal interface, excellent surface qualities,
      histological and immunohistochemical staining properties, and suitability for TEM
      examination. The technique is applicable to experimental and clinical specimens.

PMID- 9930057
TI  - Transcatheter closure of a residual postmyocardial infarction ventricular septal
      defect with the Amplatzer septal occluder.
AB  - Acute ventricular septal rupture following myocardial infarction carries a high
      mortality. Early surgery improves survival but long term outcome depends on
      residual shunting and left ventricular function. Residual shunting is common
      despite apparently successful closure and may require reoperation. Transcatheter
      closure is an established method of treating selected congenital defects but
      clinical experience of transcatheter closure in postinfarction ventricular septal
      rupture is minimal. Transcatheter closure of a residual ventricular septal defect
      was successfully done using a new device, the Amplatzer septal occluder, in a 50
      year old Indian man who had previously undergone emergency surgical repair for
      postinfarction acute ventricular septal rupture. The technique is described and
      its potential as a treatment in postinfarction ventricular septal rupture, its
      possible complications, and the important aspects of case selection and device
      design are discussed.

PMID- 9930056
TI  - Percutaneous closure of secundum atrial septal defect with a new self centering
      device ("angel wings").
AB  - OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new
      self centering device ("angel wings") for closure of secundum atrial septal
      defects (ASD II) and persistent foramen ovale in all age groups. DESIGN:
      Multicentre, prospective, nonrandomised study. PATIENTS:  INCLUSION CRITERIA:
      defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4
      mm; body weight > 10 kg; and an indication for surgical closure of secundum
      atrial septal defect. Additionally, there were compassionate indications for
      closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were
      closed by a transcatheter device consisting of two square frames made of
      superelastic nitinol wire. The frames are covered by elastic polyester fabric,
      which is sewn together at a central circle. All procedures, except for three
      interventions that were carried out under sedation, were performed under general
      anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor
      intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD
      II was present in 35 children and 15 adults. A persistent foramen ovale was
      present in 25 adults with suspected paradoxical embolism. Transcatheter closure
      was unsuccessful in three children and crossover to surgery was required.
      Residual shunts were found in 20 patients (27%) immediately after the procedure.
      A transient atrioventricular third degree block occurred in three patients (4%)
      and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm)
      was present in only three (4%) of 72 patients during follow up of 1-17 months.
      Blood clots on the right atrial disks in two patients (one required lysis) were
      seen during follow up transoesophageal echocardiography. Serious complications
      demanding surgical removal of the device occurred in three patients. One patient
      had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus
      formation due to an unfolded right atrial disk was found in a second patient and
      dislodgement of the left atrial disk resulted in a large residual shunt in a
      third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or =
      20 mm in paediatric and adult patients is feasible and effective with this new
      device. It is a promising alternative to surgical closure. Modifications of the
      design, however, seem to be mandatory as 4% of patients developed serious
      complications.

PMID- 9930058
TI  - 1:1 atrioventricular conduction in congenital complete heart block.
AB  - A female neonate with congenital complete heart block developed atrioventricular
      conduction through an accessory pathway. Despite sinus rhythm and an adequate
      heart rate she developed severe dilated cardiomyopathy and died at age 14 months.
      This case illustrates that underlying heart block can be present in individuals
      with asymptomatic Wolff-Parkinson-White syndrome and that the dilated
      cardiomyopathy that occasionally accompanies autoimmune congenital heart block is
      not primarily caused by bradycardia.

PMID- 9930059
TI  - Successful treatment of false aneurysm of a saphenous vein bypass graft with
      fistula to the anterior chest wall using "covered" intracoronary stents.

PMID- 9930060
TI  - Main stem subocclusion shortly after aortic valve replacement.

PMID- 9930061
TI  - Myocardial infarction caused by an aneurysm of the left main coronary artery
      without evidence of Kawasaki disease.

PMID- 9930062
TI  - Inappropriate management of polycythaemia in adults with cyanotic congenital
      heart disease.

PMID- 9930063
TI  - Antiganglioside antibodies in peripheral neuropathies.

PMID- 9930064
TI  - How much work do you do in a day?

PMID- 9930066
TI  - Assessing diagnostic errors: when is suspension of a pathologist justified?

PMID- 9930065
TI  - Human papillomavirus infection with particular reference to genital disease.
AB  - HPV is the commonest sexually transmitted viral infection in the United Kingdom
      and as such poses a major public health problem. In addition to the potential
      physical morbidity associated with genital warts, abnormal cervical cytology, and
      anogenital dysplasia and neoplasia, the associated psychological morbidity should
      not be forgotten. Although our knowledge of viral function and disease
      pathogenesis has advanced appreciably in recent years, we are still some way from
      developing an in vitro method of viral propagation. Vaccination against HPV
      infection will hopefully be achieved within the next 10 years, but a prevention
      and treatment strategy which is appropriate for both developed and developing
      nations must be our major long term goal.

PMID- 9930067
TI  - PCR-ELISA for the early diagnosis of invasive pulmonary aspergillus infection in
      neutropenic patients.
AB  - AIM: To evaluate a newly developed aspergillus mitochondrial gene PCR-ELISA assay
      for the early diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic
      patients. METHODS: The aspergillus mitochondrial gene was chosen for the
      amplification target for use with a solution hybridisation assay with
      colorimetric end stage detection in microtitre plate format (PCR-ELISA). The
      study group comprised neutropenic patients undergoing febrile episodes not
      responding to standard antibacterial antibiotics. Patients underwent computed
      tomography and bronchoscopy. Bronchoalveolar lavage (BAL) fluids were examined by
      culture and PCR. RESULTS: The aspergillus mitochondrial gene PCR-ELISA was both
      sensitive (100%) and specific (100%) for IPA in neutropenic patients. All 12
      patients with definite or probable IPA had PCR positive BAL fluids. None of the
      patients with undiagnosed or confirmed infections of other aetiologies were
      mitochondrial PCR positive. Speciation based upon amplicon size difference was
      possible. CONCLUSIONS: Aspergillus mitochondrial DNA PCR-ELISA on BAL fluid is
      useful in the early diagnosis of IPA in neutropenic patients alone or,
      potentially, as an indication for thoracic computed tomography.

PMID- 9930068
TI  - Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae
      antigens within inflammatory bowel disease tissues.
AB  - BACKGROUND: Escherichia coli, listeria, and streptococcal antigens have been
      found in Crohn's disease tissues. Antibodies to Klebsiella pneumoniae have been
      found in patients with inflammatory bowel disease and ankylosing spondylitis. The
      presence of these bacterial antigens in Crohn's granulomas would be of
      aetiological interest, while their presence in ulcers alone would be more likely
      to indicate secondary infection. AIM: To investigate inflammatory bowel disease
      tissues for the presence of these bacteria. METHODS: Formalin fixed, paraffin
      processed sections from 53 patients (19 ulcerative colitis, 23 Crohn's disease;
      11 normal tissues from cancer resections) were studied by immunohistochemistry.
      Control tissue consisted of normal human small bowel injected submucosally with
      either E coli, Listeria monocytogenes, Proteus mirabilis, or Klebsiella
      pneumoniae serotypes K2, 3, 17, 21, 26, 36, and 50, and colonic biopsies from a
      child with E coli 0114 infection. Tissues were stained by Gram-Twort, and with
      specific antibodies for E coli (Dako B357), L monocytogenes (Difco 2302-50), and
      K pneumoniae (Biogenesis 5580-5208) using an immunoperoxidase technique. RESULTS:
      Positive staining for E coli was observed on the luminal surface epithelium and
      in ulcers in 35% of Crohn's disease patients, 26% of ulcerative colitis patients,
      and no normal controls. Superficial staining for L monocytogenes was observed in
      one case of ulcerative colitis only. Staining for K pneumoniae was observed in
      one case of ulcerative colitis and one of Crohn's disease. No granulomas, giant
      cells, or germinal centres stained positively for any of the three bacterial
      antigens. CONCLUSIONS: These data do not support a primary role for E coli, L
      monocytogenes, and K pneumoniae in inflammatory bowel disease. The presence of E
      coli antigens in ulcers suggests secondary infection in these lesions.

PMID- 9930069
TI  - Helicobacter pylori and Epstein-Barr virus infection and the p53 tumour
      suppressor pathway in gastric stump cancer compared with carcinoma in the non
      operated stomach.
AB  - AIM: To evaluate similarities and differences between gastric stump cancer and
      conventional carcinoma in the non-operated stomach. METHODS: 26 stump carcinomas
      were compared with 24 conventional stomach cancers. Stage, histological type, and
      demographics were comparable in the two groups. Expression of p53 and p21
      Waf1/Cip1 was evaluated by immunohistochemical staining. Helicobacter pylori
      infection was evaluated by examining haematoxylin-eosin stained slides and
      immunohistochemistry. Epstein-Barr virus infection was evaluated by RNA in situ
      hybridisation. RESULTS: Expression of p53 and p21-Waf1/Cip1 was similar in both
      groups and positive in more than half of the patients. H pylori infection was
      observed in six stump carcinomas and 17 conventional carcinomas in the intact
      stomach (p < 0.01). RNA in situ hybridisation (EBER1-ISH) for Epstein-Barr virus
      was positive in nine stump carcinomas and two carcinomas in the non-operated
      stomach (p < 0.05). CONCLUSIONS: There appear to be aetiological differences
      between stump carcinoma and cancer in the intact stomach. Further study of these
      differences may improve our understanding of gastric carcinogenesis in general.

PMID- 9930070
TI  - MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR
      and c-erbB-2 expression and correlates with poor survival in node positive
      patients.
AB  - AIM: To examine tumour samples immunohistochemically for MUC1 (episialin),
      epidermal growth factor receptor (EGFR), and c-erbB-2, since the disruption of
      the cell-cell adhesion system by MUC1 and the c-erbB oncoprotein family is known
      to be important in the development of metastasis in human cancers. METHODS: 93
      tumour samples from patients with early stage non-small cell lung cancer treated
      with surgery alone were examined for episialin, EGFR, and c-erbB-2. RESULTS:
      Episialin depolarised expression did not correlate with any of the
      histopathological variables examined (T,N stage, grade, histology, Ki67
      proliferation index). No correlation was observed between episialin and EGFR or c
      erbB-2 expression. Survival analysis showed that episialin depolarised expression
      correlated with poor prognosis (p = 0.003), especially in squamous cell cases (p
      = 0.0003). Episialin expression defined a group of patients with poor prognosis
      in the node positive category (p = 0.003). In multivariate analysis episialin was
      the most significant independent prognostic factor (p = 0.007), followed by N
      stage (p = 0.04). CONCLUSIONS: Depolarised expression of episialin is associated
      with poor outcome in early stage non-small cell lung cancer. Despite the similar
      activity on the cadherin cell-cell adhesion system, the expression of episialin
      and c-erbB oncoproteins is likely to be activated within different pathogenic
      pathways.

PMID- 9930071
TI  - Association of pure red cell aplasia with T large granular lymphocyte leukaemia.
AB  - AIM: To define the relation between T large granular lymphocyte (T-LGL) leukaemia
      and pure red cell aplasia in Chinese patients. METHODS: Patients with T-LGL
      leukaemia were identified from a consecutive series of Chinese patients with
      chronic lymphoproliferative disorders. The diagnosis of T-LGL leukaemia was based
      on typical morphological and immunophenotypical features, and confirmed by the
      detection of clonal T cell receptor gene rearrangement. The clinicopathological
      features, response to treatment, and long term follow up were also examined.
      RESULTS: Five patients were identified as having T-LGL leukaemia from a
      consecutive series of 33 Chinese patients with chronic lymphoproliferative
      disorders. The median follow up time was 45 months. An obvious lymphocytosis was
      present in only two cases, although an increase in large granular lymphocytes in
      the peripheral blood was found in four. In one case, the LGL count was within the
      normal range. Epstein-Barr virus encoded early nuclear RNA was negative in all
      the cases. There was no evidence of rheumatoid arthritis, and none of the
      patients presented with recurrent infections. On follow up, pure red cell aplasia
      occurred at some stage of the disease in all the patients. This responded to
      treatment with cyclosporin A in two and with antithymocyte globulin in one. Two
      patients remained transfusion dependent. CONCLUSIONS: In contrast to Western
      patients, Chinese patients with T-LGL leukaemia do not appear to suffer from
      rheumatoid arthritis and recurrent infections, but pure red cell aplasia is a
      major cause of morbidity in this ethnic group.

PMID- 9930072
TI  - Hepatitis G virus infection in lymphoma and in blood donors.
AB  - AIMS: To determine whether the recently described flavivirus, hepatitis G virus
      (HGV), might contribute to the pathogenesis of lymphoma by testing for the
      presence of HGV RNA in sera from patients attending lymphoma clinics; to compare
      the incidence of HGV RNA in lymphoma patients with that in normal blood donors;
      and to look for potential risk factors for HGV infection and for evidence of
      hepatic disease in the HGV positive patients. METHODS: Sera were examined from 76
      patients with lymphoma and 100 blood donors for the presence of HGV RNA using
      reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: HGV RNA was
      detected in 10% of patients' sera, but only in 1% of blood donor samples. HGV
      infection was found in patients with various different types of lymphoma,
      including Hodgkin's disease and non-Hodgkin's lymphoma. The majority (75%) of
      patients who were HGV PCR positive had undergone transfusion, but only 30% of
      those who were HGV PCR negative had received blood products. In addition, the
      number of donor exposures per HGV positive patient was approximately twice that
      of the HGV negative group. CONCLUSIONS: The data suggest (1) that HGV is present
      in the normal blood donor population; (2) that patients with lymphoma are at risk
      of acquiring HGV because of their exposure to blood products; and (3) that
      persistent HGV infection does not appear to cause serious liver disease in these
      patients.

PMID- 9930073
TI  - The limited difference between keratin patterns of squamous cell carcinomas and
      adenocarcinomas is explicable by both cell lineage and state of differentiation
      of tumour cells.
AB  - AIM: To study the differentiation of epithelial tissues within their histological
      context, and to identify hypothetically, on the basis of keratin pattern, the
      putative tissue origin of a (metastatic) carcinoma. METHODS: Using well
      characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19,
      which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and
      14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin
      patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas
      originating from various epithelial tissues were characterised. RESULTS: The
      predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In
      addition, these keratins were also abundantly present in squamous cell carcinomas
      of the lung, cervix, and rectum and, to a lesser extent, of the larynx,
      oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10,
      13, and 14 were present in almost all squamous cell carcinomas, but also focally
      in some of the adenocarcinomas studied. CONCLUSIONS: There is a limited
      differential expression of distinctive keratin filaments between squamous cell
      carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that
      originate from columnar epithelium by squamous metaplasia gain the keratins of
      squamous cells but retain the keratins of columnar epithelial cells. However, the
      simultaneous expression of two of three squamous keratins (4, 10, and 13)
      identifies a squamous cell carcinoma, and thus might be useful in solving
      differential diagnostic problems.

PMID- 9930074
TI  - The prognostic significance of beta human chorionic gonadotrophin and its
      metabolites in women with cervical carcinoma.
AB  - AIMS: To examine long term survival of women with primary and recurrent cervical
      carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta
      human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the
      tumours, to determine the suitability of these markers for assessing prognosis.
      METHODS: This was a prospective observational study undertaken in a
      gynaecological oncology centre: 57 women with primary cervical cancer and 42 with
      recurrent disease were recruited between January 1990 and September 1992. Kaplan
      Meier survival analysis with the log rank test was used to assess survival
      differences with survival rate given per year of follow up. RESULTS: In primary
      disease, the four year survival for the beta-core negative group was 79%,
      compared with 14% for the beta-core positive group (p = 0.001). This was still
      significant for early stage disease or squamous lesions alone. In recurrent
      disease, beta-core positivity was not prognostically significant.
      Immunohistochemistry was of no prognostic significance in either group.
      CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of
      primary cervical cancer but not of recurrent disease. A large prospective study
      of urinary beta-core in early stage cervical cancer is needed to determine
      whether it can be used as an index for modifying treatment.

PMID- 9930075
TI  - The value of a thorough protocol in the investigation of sudden infant deaths.
AB  - AIMS: To review the diagnostic value of using a thorough necropsy protocol for
      the investigation of sudden infant deaths, with particular emphasis on the value
      of routine ancillary laboratory investigations. METHODS: The necropsy and related
      records of all neonatal, infant, and young childhood deaths (under three years)
      referred for medicolegal investigation at Dundee from 1990 to early 1998 were
      reviewed retrospectively. Relevant positive and negative findings were abstracted
      from the police reports, hospital medical records, necropsy reports, and the
      results of routine bacteriological, virological, toxicological, and biochemical
      laboratory investigations. RESULTS: Within the study period, 63 deaths presented
      as apparent "cot deaths," nine as suspected homicides, nine as neonatal deaths,
      and 14 in some other manner. An adequate cause of death was identified on the
      basis of necropsy and laboratory investigations in 35% of the 63 apparent cot
      deaths, leaving 63% to be finally categorised as sudden infant death syndrome
      (SIDS). Ten (16%) of the apparent cot deaths were explained on the sole basis of
      unexpected positive microbiological findings, mostly pneumococcal or
      meningococcal meningitis and/or septicaemia. Petechial haemorrhages were
      identified at one or more intrathoracic site in 90% of SIDS and in 55% of
      explained cot deaths. CONCLUSIONS: Early and extensive laboratory investigations
      performed routinely in apparent cot deaths provide an unexpectedly high positive
      diagnostic yield. Routine early bacteriological culture of the CSF (by cisternal
      puncture) and blood before necropsy should be mandatory in the investigation of
      all sudden infant deaths.

PMID- 9930076
TI  - Internal quality assurance activities of a surgical pathology department in an
      Australian teaching hospital.
AB  - AIM: To assess the role of a quality assurance programme in improving the service
      provided by a surgical pathology department. METHODS: A continuous internal
      quality assurance study of the activities of an anatomical pathology department
      in an Australian teaching hospital was undertaken over a five year period. This
      addressed all steps involved in the production of a surgical pathology report.
      These were addressed in an open forum which included technical, scientific,
      clerical, and medical staff. Minor errors not needing immediate action were
      discussed and incorporated into laboratory practice. For major discrepancies with
      potential implications for patient management supplementary reports were issued
      and the relevant clinician informed of the outcome. RESULTS: Comprehensive peer
      review of 8.9% of the total workload of the department (3530 cases) and all the
      frozen sections (916 cases) over a period of five years, beginning in 1991, led
      to comments on some aspects of the original report by the reviewer in 19.6% of
      the cases. The great majority of the comments were minor, concerning issues
      related to the microscopic findings (4%), macroscopic description (3.1%),
      clerical aspects (3%), typographical errors (3%), coding errors (2.7%), technical
      errors including poor sections and incorrect labelling (1.7%), inadequate
      clinical history (1.2%), and incomplete or incomprehensible diagrams (0.9%). In
      two cases (0.05%) the original report did not state proximity of the tumour to
      surgical margins and in three of the frozen sections (0.3%) the original
      diagnosis was incorrect. However, in these cases the frozen section assessment
      did not alter the overall management of the cases. CONCLUSIONS: This study
      highlights the importance of a review system in detecting errors in surgical
      pathology reporting. Recognition of the fact that surgical pathology is not
      infallible has improved the end product. It has also minimised interobserver
      variability in the department, resulting in a uniform approach among the
      pathologists to macroscopic description, specimen sampling, special stains, and
      histological reporting.

PMID- 9930077
TI  - Jejuno-ileal bypass, enteric hyperoxaluria, and oxalate nephrosis: a role for
      polarised light in the renal biopsy.
AB  - Enteric hyperoxaluria, a complication of jejuno-ileal bypass, is associated with
      renal failure owing to oxalate nephrosis or tubulo-interstitial nephritis. A 54
      year old woman developed renal failure 17 months after jejuno-ileal bypass for
      morbid obesity. Renal biopsy showed widespread acute on chronic damage to the
      tubulo-interstitial compartment with extensive deposition of oxalate crystals.
      The extent of oxalate deposition was only evident on polarisation of the biopsy.

PMID- 9930078
TI  - Unilateral and segmental localised polycystic kidney disease.
AB  - Unilateral and segmental localised polycystic disease is a rare type of cystic
      disease of the kidney. It takes the form of a segmental cystic abnormality in one
      kidney morphologically identical to the autosomal dominant adult form of
      polycystic kidney disease. The clinical, radiological, and pathological
      appearances of a case are described. The differential diagnosis and a possible
      pathogenic mechanism are discussed.

PMID- 9930079
TI  - Local recurrence of a phyllodes tumour of the breast presenting with widespread
      differentiation to a telangiectatic osteosarcoma.
AB  - Osteogenic sarcomas of the breast are extremely rare and need to be distinguished
      from a variety of breast lesions producing metaplastic bone. A 50 year old
      patient presented with a painless lump in her right breast after twice previously
      having undergone local excision of a phyllodes tumour at this site. Following
      radiological and cytological investigation, excision was advised. Histology
      showed focal remnants of the previously excised phyllodes tumour in continuity
      with areas of widespread differentiation towards a telangiectatic osteosarcoma.
      So far this is a unique morphological endpoint.

PMID- 9930080
TI  - Anaerobic infections of the urinary tract: are they being missed?
AB  - Routine anaerobic culture of urine identified the urinary tract as the primary
      focus of sepsis in a postoperative patient with Bacteroides fragilis septicaemia.
      Specimens of urine from six other symptomatic patients grew > 10(8) cfu/litre of
      a Bacteroides species in pure growth. The significance of these isolates is
      discussed. Multipoint technology and the availability of anaerobic work stations
      have facilitated anaerobic culture and reduced its cost. The incorporation of
      anaerobic culture of urine into routine laboratory practice may be clinically
      valuable and should be considered.

PMID- 9930081
TI  - Clinical experience of trainees in chemical pathology: a survey of junior medical
      staff in the United Kingdom.

PMID- 9930082
TI  - Decentralised anticoagulant care.

PMID- 9930083
TI  - Fine needle aspiration and the diagnosis of non-Hodgkin's lymphoma.

PMID- 9930084
TI  - Effect of measurement error on epidemiological studies of environmental and
      occupational exposures.
AB  - Random error (misclassification) in exposure measurements usually biases a
      relative risk, regression coefficient, or other effect measure towards the null
      value (no association). The most important exception is Berkson type error, which
      causes little or no bias. Berkson type error arises, in particular, due to use of
      group average exposure in place of individual values. Random error in exposure
      measurements, Berkson or otherwise, reduces the power of a study, making it more
      likely that real associations are not detected. Random error in confounding
      variables compromises the control of their effect, leaving residual confounding.
      Random error in a variable that modifies the effect of exposure on health--for
      example, an indicator of susceptibility--tends to diminish the observed
      modification of effect, but error in the exposure can create a supurious
      appearance of modification. Methods are available to correct for bias (but not
      generally power loss) due to measurement error, if information on the magnitude
      and type of error is available. These methods can be complicated to use, however,
      and should be used cautiously as "correction" can magnify confounding if it is
      present.

PMID- 9930085
TI  - Association between exposure to crystalline silica and risk of sarcoidosis.
AB  - OBJECTIVES: The possibility of an association between exposure to silica and
      autoimmune diseases has recently come under discussion. In the following case
      referent study, a cohort exposed to diatomaceous earth and cristobalite provided
      an opportunity to evaluate such an exposure with reference to sarcoidosis.
      METHODS: The inhabitants of a district served by a single healthcare centre and a
      hospital formed the study base. A diatomaceous earth plant is located in this
      community and the medical institutions are responsible for primary and secondary
      health care of the population. Cases of sarcoidosis were identified from the
      hospital records according to certain clinical, radiological, and histological
      criteria. Referents were selected randomly from the population of the district.
      Information on exposure to crystalline silica, cristobalite, was obtained by
      record linkage of the cases and referents with a file which included all present
      and past workers at the diatomaceous earth plant and those who had worked at
      loading vessels with the product from the plant. RESULTS: Eight cases of
      sarcoidosis were found, six of which were in the exposed group. Of the 70
      referents, 13 were exposed. The odds ratio (95% confidence interval) was 13.2
      (2.0 to 140.9). CONCLUSION: The odds ratios were high and there were some
      indications of a dose-response relation which will hopefully encourage further
      studies. To our knowledge this is the first study to indicate a relation between
      sarcoidosis and exposure to the crystalline silica, cristobalite.

PMID- 9930086
TI  - Impact of exposure to insulation wool on lung function and cough in Swedish
      construction workers.
AB  - OBJECTIVES: To investigate whether application of insulation wool adversely
      affects lung volumes and increases the occurrence of symptoms of airway
      irritation. METHODS: Data from nationwide health check ups in 1981-93 of male
      construction workers born in 1955 or later were used to investigate cross
      sectional (n = 96,004) and longitudinal (n = 26,298) associations between lung
      volumes, vital capacity (VC), and forced expiratory volume in one second (FEV1)
      and exposure to insulation wool by combining a job exposure matrix (JEM) and self
      reported exposure. Data on 12 month prevalence of persistent cough not associated
      with the common cold was available for the period 1989-92. Potential confounding
      from smoking, exposure to asbestos, silica, and isocyanates, was considered in
      the analyses. RESULTS: For those in the highest exposure category (self reported
      duration of exposure of > or = 11 years, and high exposure according to the JEM)
      VC was on average 2.5 cl lower (95% CI -6.5 to 1.5) than in those with no
      exposure. The corresponding figures for FEV1 was -2.4 cl (95% CI -6.1 to 1.3). In
      the longitudinal analyses, the yearly change in VC between the first and last
      spirometry for those in the highest exposure category was 0.50 cl (95% CI -0.97
      to 1.98) less than in the unexposed category. The corresponding figure for FEV1
      was 0.89 cl (95% CI - 0.70 to 2.06). High exposure to insulation wool, asbestos,
      or silica, during the 12 months preceding the check up was associated with
      increased odds ratios (ORs) for persistent cough of the same magnitude as current
      smoking. CONCLUSIONS: The results indicate no effects on VC or FEV1 from exposure
      to insulation wool. Recent exposure to insulation wool, asbestos, and silica was
      associated with an increased prevalence of persistent cough.

PMID- 9930087
TI  - Prevalence and predictors of work related respiratory symptoms in workers exposed
      to organic dusts.
AB  - OBJECTIVES: The aims of this study were to document the prevalence of work
      related upper and lower respiratory tract symptoms in workers exposed to organic
      dusts and to identify variables predictive of their occurrence. METHODS: A cross
      sectional survey with an administered questionnaire (a previously validated
      adaptation of the Medical Research Council (MRC) respiratory questionnaire) was
      performed. Symptoms were classified as work related by their periodicity.
      Demographic data, smoking habits, and occupational histories were recorded.
      Personal exposures to dust and endotoxin were measured and individual subjects
      ascribed an exposure value specific to occupation, site and industry. Cox's
      regression techniques were used to identify variables predictive of work related
      upper and lower respiratory tract symptoms. Information was stored using Dbase 3
      and analysed with SPSS. RESULTS: 1032 Workers (93% of the target population) were
      studied in nine different industries. The highest prevalences of work related
      lower respiratory tract symptoms (38.1%), upper respiratory tract symptoms
      (45.2%), and chronic bronchitis (15.5%) were found among poultry handlers. White
      workers were significantly more likely to complain of upper and lower respiratory
      tract symptoms. An individual in the swine confinement industry had a symptom
      complex compatible with byssinosis. Increasing current personal exposures to dust
      or endotoxin were found to be predictive of upper and lower respiratory tract
      symptoms, chronic bronchitis, and byssinosis. In a univariate analysis a relation
      between current exposures and the organic dust toxic syndrome was found. Present
      smoking and previously documented respiratory tract illness were significantly
      predictive of work related lower respiratory tract symptoms. Women were more
      likely to report work related upper respiratory tract symptoms. CONCLUSIONS:
      People exposed to organic dusts may have a high prevalence of work related
      respiratory tract symptoms which are related to dust exposures and smoking
      habits. Action should be taken to reduce exposures to dust and endotoxin and
      stopping smoking should be promoted among workers exposed to organic dusts to
      reduce morbidity.

PMID- 9930088
TI  - Change in obstructive pulmonary function as a result of cumulative exposure to
      welding fumes as determined by magnetopneumography in Japanese arc welders.
AB  - OBJECTIVES: To examine the effect of chronic exposure to welding fumes on
      pulmonary function by a direct estimate of fumes accumulated in the lungs.
      METHODS: The strength of the residual magnetic field of externally magnetised
      lungs (LMF) was used as an estimate of fumes accumulated in the lungs. The
      results of forced spirometry manoeuvres obtained in 143 of 153 male welders in
      the original sample were cross sectionally evaluated according to LMF. Seven
      conventional forced spirogram indices and two time domain spirogram indices were
      used as pulmonary function indices, and height squared proportional correction
      was performed when necessary. RESULTS: The distribution of LMF values was
      considerably skewed towards positive. There was a weak but significant positive
      relation between age and log transformed LMF. Obstructive pulmonary function
      indices correlated well with LMF. After adjustment for age and smoking, however,
      a significant association with LMF was only found with percentage rate of forced
      expiratory volume in one second (FEV1%) divided by forced vital capacity (FVC)
      and mu, and average component of assumed time constant distribution of lung
      peripheral units. Neither FVC nor vital capacity (VC), as indices of restrictive
      disorders, showed a significant association with LMF. Based on the results of
      multiple regression analyses, a 0.6% decrease in FEV1% and 0.039 unit increase in
      mu were expected for each doubling of LMF. CONCLUSION: Obstructive changes in
      pulmonary function were found to be related to level of cumulative exposure to
      welding fume in male Japanese arc welders after controlling for age and smoking,
      assuming that LMF adequately reflects accumulation of welding fumes in the lungs.

PMID- 9930089
TI  - Lung health among plumbers and pipefitters in Edmonton, Alberta.
AB  - OBJECTIVES: A cross sectional study was undertaken to assess lung health among
      plumbers and pipefitters. Respiratory symptoms, lung function, and radiographic
      changes among 99 actively employed plumbers and pipefitters with > or = 20 years
      of union membership were compared with 100 telephone workers. METHODS: A
      respiratory symptom questionnaire was administered, including smoking and
      occupational histories. Spirometry was conducted according to standard criteria.
      Posteroanterior chest radiographs were evaluated by two experienced chest
      physicians, with a third arbitrating disagreed films. Members of the union were
      categorised as pipefitters (n = 57), plumbers (n = 16), or welders (n = 26),
      based on longest service, and compared with the telephone workers and internally
      (between groups). Lung health was also compared with employment in several work
      sectors common to Alberta for time, and for time weighted by exposure to dust and
      fumes. RESULTS: Compared with the telephone workers, plumbers and pipefitters had
      more cough and phlegm, lower forced vital capacity, and more radiographic changes
      (20% with any change), including circumscribed (10%) and diffuse pleural
      thickening (9%). None of the plumbers and pipefitters had small radiographic
      opacities. Among the three subgroups of workers, plumbers had the highest
      prevalence of radiographic changes. Both plumbers and pipefitters showed higher
      odds ratios for cough and phlegm than the welders. No differences between groups
      were found for lung function. Indicators of lung health were not related to work
      in any sector. CONCLUSIONS: Plumbers and pipefitters had increased prevalence of
      symptoms suggestive of an irritant effect with no evidence of bronchial
      responsiveness. The chest radiographs showed evidence of asbestos exposure,
      especially in the plumbers, but at lower levels than previously reported. Health
      screening programmes for these workers should be considered, although the
      logistical problems associated with screening in this group would be
      considerable.

PMID- 9930090
TI  - Risk factors for sensitisation and respiratory symptoms among workers exposed to
      acid anhydrides: a cohort study.
AB  - OBJECTIVES: To examine the relation between exposure to acid anhydrides and the
      risk of developing immediate skin prick test responses to acid anhydride human
      serum albumin (AA-HSA) conjugates or work related respiratory symptoms; to assess
      whether these relations are modified by atopy or smoking. METHODS: A cohort of
      506 workers exposed to phthalic (PA), maleic (MA), and trimellitic anhydride
      (TMA) was defined. Workers completed questionnaires relating to employment
      history, respiratory symptoms, and smoking habits. Skin prick tests were done
      with AA-HSA conjugates and common inhalant allergens. Exposure to acid anhydrides
      was measured at the time of the survey and a retrospective exposure assessment
      was done. RESULTS: Information was obtained from 401 (79%) workers. Thirty four
      (8.8%) had new work related respiratory symptoms that occurred for the first time
      while working with acid anhydrides and 12 (3.2%) were sensitised, with an
      immediate skin prick test reaction to AA-HSA conjugates. Sensitisation to acid
      anhydrides was associated with work related respiratory symptoms and with smoking
      at the time of exposure to acid anhydride. When all subjects were included and
      all three acid anhydrides were taken into account there was no consistent
      evidence for an exposure-response relation, but with the analysis restricted to a
      factory where only TMA was in use there was an increased prevalence of
      sensitisation to acid anhydrides and work related respiratory symptoms with
      increasing full shift exposure. This relation was apparent within the current
      occupational exposure standard of 40 micrograms.m-3 and was not modified
      significantly by smoking or atopy. CONCLUSIONS: Intensity of exposure and
      cigarette smoking may be risk factors for sensitisation to acid anhydrides.
      Exposure is also a risk factor for respiratory symptoms. As there was evidence
      for sensitisation to TMA at full shift exposures within the occupational exposure
      standard this standard should be reviewed.

PMID- 9930091
TI  - Retrospective exposure assessment for a cohort study into respiratory effects of
      acid anhydrides.
AB  - OBJECTIVES: To estimate past exposure to phthalic (PA), trimellitic (TMA) and
      maleic anhydride (MA) in three alkyd resin and one cushioned flooring factory to
      estimate exposure-response relations in a retrospective cohort study. METHODS:
      Personal exposure measurements were carried out in 1992 and quantitative and
      qualitative information on past exposure and production processes were collected.
      Job titles were ranked by decreasing exposure and amalgamated into job categories
      and exposure groups. Multiplication factors for back calculating past exposure
      levels were estimated with past exposure data, or if no such data were available
      these factors were estimated by a panel of occupational hygienists. Exposure
      levels were back calculated starting with the exposure levels in 1992. RESULTS:
      High exposures to PA were estimated to have occurred among workers operating the
      PA melting pots in factory 1 (estimated exposure in 1960-9 was 2480 micrograms.m
      3). Highest concentrations of TMA were estimated to have occurred among the ink
      mixers in factory 2 from 1979 to 1986 (554 micrograms.m-3). Exposure in most
      other job titles was thought to be fairly constant over time for PA, TMA, and MA.
      CONCLUSIONS: Exposure to acid anhydride at these factories has fallen during the
      period covered by the study. However, it is estimated that in only one job in
      factory 2 did past exposure to acid anhydride exceed the current occupational
      exposure standard. Accuracy of the estimated exposure is limited by a paucity of
      reliable past exposure data.

PMID- 9930092
TI  - Urban air pollution and cardiopulmonary ill health: a 14.5 year time series
      study.
AB  - OBJECTIVES: To examine possible associations between daily concentrations of
      urban air pollutants and hospital emergency admissions and mortality due to
      cardiac and pulmonary disease. METHODS: A time series study was conducted in the
      City of Edinburgh, which has a population of about 450,000. Poisson log linear
      regression models were used to investigate the relation of the daily event rate
      with daily air pollution concentrations of sulphur dioxide (SO2) and black smoke
      from 1981 to 1995, and of nitrogen dioxide (NO2), ozone (O3), carbon monoxide
      (CO), and particulate matter (PM10) from 1992 to 1995. Adjustments were made for
      seasonal and weekday variation, daily temperature, and wind speed. RESULTS: The
      most significant findings were positive associations over the period 1981-95
      between black smoke as a mean of the previous three days and daily all cause
      mortality in people aged > or = 65, and respiratory mortality also in this age
      group (3.9% increase in mortality for a 10 micrograms/m3 increment in black
      smoke). For hospital emergency admissions between 1992 and 1995 the two most
      significant findings (p < 0.05) were for cardiovascular admissions of people aged
      > or = 65 which showed a positive association with PM10 as a mean of the 3
      previous days, and a negative association with O3 as a mean of the previous three
      days. Analyses of outcomes based on linkage with previous cardiorespiratory
      emergency admissions did not show substantially different results. CONCLUSION:
      These data suggest that in the City of Edinburgh, after correction for
      confounders, there was a small but significant association between concentrations
      of black smoke and respiratory mortality in the older age group, probably
      attributable to higher pollution levels in the early part of the study period.
      There were also generally weak and variable associations between day to day
      changes in concentrations of urban air pollutants at a single central point and
      emergency hospital admission rates from cardiac and respiratory disease.

PMID- 9930093
TI  - Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers
      occupationally exposed to benzene.
AB  - OBJECTIVES: Animal inhalation studies and theoretical models suggest that the
      pattern of formation of benzene metabolites changes as exposure to benzene
      increases. To determine if this occurs in humans, benzene metabolites in urine
      samples collected as part of a cross sectional study of occupationally exposed
      workers in Shanghai, China were measured. METHODS: With organic vapour monitoring
      badges, 38 subjects were monitored during their full workshift for inhalation
      exposure to benzene. The benzene urinary metabolites phenol, catechol,
      hydroquinone, and muconic acid were measured with an isotope dilution gas
      chromatography mass spectroscopy assay and strongly correlated with
      concentrations of benzene air. For the subgroup of workers (n = 27) with urinary
      phenol > 50 ng/g creatinine (above which phenol is considered to be a specific
      indicator of exposure to benzene), concentrations of each of the four metabolites
      were calculated as a ratio of the sum of the concentrations of all four
      metabolites (total metabolites) and were compared in workers exposed to > 25 ppm
      v < or = 25 ppm. RESULTS: The median, 8 hour time weighted average exposure to
      benzene was 25 ppm. Relative to the lower exposed workers, the ratio of phenol
      and catechol to total metabolites increased by 6.0% (p = 0.04) and 22.2% (p =
      0.007), respectively, in the more highly exposed workers. By contrast, the ratio
      of hydroquinone and muconic acid to total metabolites decreased by 18.8% (p =
      0.04) and 26.7% (p = 0.006), respectively. Similar patterns were found when
      metabolite ratios were analysed as a function of internal benzene dose (defined
      as total urinary benzene metabolites), although catechol showed a more complex,
      quadratic relation with increasing dose. CONCLUSIONS: These results, which are
      consistent with previous animal studies, show that the relative production of
      benzene metabolites is a function of exposure level. If the toxic benzene
      metabolites are assumed to be derived from hydroquinone, ring opened products, or
      both, these results suggests that the risk for adverse health outcomes due to
      exposure to benzene may have a supralinear relation with external dose, and that
      linear extrapolation of the toxic effects of benzene in highly exposed workers to
      lower levels of exposure may underestimate risk.

PMID- 9930094
TI  - Dementia and occupational exposure to organic solvents.
AB  - OBJECTIVES: To investigate whether occupational exposure to organic solvents
      increases the risk of dementia. METHODS: Cases of dementia were identified from
      the computed tomography records of eight neuroradiology centres in England and
      Wales, and were compared with two sets of controls investigated at the same
      centres. The first set of controls were patients with brain cancer and the second
      set were patients with other disorders that were not chronically disabling.
      Lifetime occupational histories were obtained through a postal questionnaire
      completed by the subjects or their next of kin. Associations between dementia and
      occupation were examined by logistic regression. RESULTS: Usable questionnaires
      were returned for 204 (61%) of the cases, 225 (51%) of the controls with brain
      cancer, and 441 (61%) of the other controls. The findings with each of the two
      sets of controls were similar. In comparison with all controls combined, cases
      had less often worked ever as a painter or printer (odds ratio (OR) 0.6, 95%
      confidence interval (95% CI) 0.3 to 1.2), and were less likely to have worked for
      > 1 year as a printer, painter, or launderer or dry cleaner (OR 0.6, 95% CI 0.3
      to 1.4). CONCLUSIONS: These findings provide no support for the hypothesis that
      occupational exposure to solvents is a cause of dementia. An excess risk in
      subsets of workers with extremes of exposure cannot be discounted, but the data
      indicate that any influence of exposure to solvents on the overall incidence of
      severe dementia in the general population of England and Wales is small.

PMID- 9930095
TI  - Symptoms of hand-arm vibration syndrome in gas distribution operatives.
AB  - OBJECTIVES: To survey the prevalence and severity of hand-arm vibration syndrome
      symptoms (HAVS), and to estimate past and current exposure to hand held vibrating
      tools in a sample of gas distribution operatives breaking and re-instating road
      surfaces. METHODS: 153 gas distribution operatives (participation rate 81%) from
      three company districts were assessed by an administered questionnaire, a
      clinical examination, and a simple cold challenge test to the hands. Exposure
      histories were taken aided by a picture album of past and current tools.
      Information was obtained from several sources on the likely vibratory
      characteristics of those tools. Estimates were thus obtained of the frequency of
      blanching and neurological complaints in operatives, and of their lifetime hours
      of exposure and lifetime dose of vibration. RESULTS: On average, the sample had
      spent 16 years in employment involving use of vibratory tools. 24% had symptoms
      or signs of blanching after use of tools in the industry; 46% had troublesome
      persistent complaints of paraesthesiae or numbness, and these symptoms extended
      into the hands or arms in 18% of workers. In 5.9% the distribution of symptoms
      was suggestive of carpal tunnel syndrome; and of ulnar nerve entrapment in a
      further 3.9%. The risks of blanching and neurological complaints rose
      significantly with lifetime hours of use of vibrating tools and lifetime dose of
      vibration. Symptoms were generally mild and apparent only after a prolonged
      interval, but there were exceptions, and cases had occurred after lower recent
      exposures. CONCLUSIONS: It has been suggested that aspects of the gas
      distribution operative's work mitigate against the risk normally anticipated from
      use of pneumatic road breaking tools. By contrast our data suggest that symptoms
      of HAVS do occur, given sufficient exposure, a finding relevant not only to gas
      supply workers, but also to workers from other industries who break and repair
      road surfaces.

PMID- 9930096
TI  - Bank bone, infections and HIV.

PMID- 9930097
TI  - Bone bank service in Finland. Experience of bacteriologic, serologic and clinical
      results of the Turku Bone Bank 1972-1995.
AB  - 560 bones were harvested by The Turku Bone Bank between 1972-1995. It was started
      with massive allografts for bone tumor surgery, but today most are femoral heads
      for hip revision surgery. The increase in harvested bones nearly trebled from
      1984-1989 to 1990-1995. Only 1 positive hepatitis C test was found. There were no
      hepatitis B or HIV positive donors. The incidence of discarding after screening
      was 24%, with positive bacterial growth (8%, usually Staphylococcus epidermidis)
      as the commonest reason. 2 massive grafts with negative cultures when harvesting
      were positive after thawing and resulted in deep infection. 369 allografts were
      transplanted. The infection rate of massive allografts for bone tumor surgery was
      5/63 in 1973-1995, and 2/52 in 1985-1995. The infection rate for hip revision
      surgery was 3.4%. The clinical functional results correspond to those reported in
      larger international series.

PMID- 9930098
TI  - Retesting of bone donors 2 months after donation guarantees sufficient safety of
      bone allografts.
AB  - Both allogeneic bone grafting and blood transfusion may transmit infections from
      the donor to the recipient. The most effective means to reduce the risk of
      infection is careful donor selection and screening of donors for markers of
      infection. The risk of blood transfusion-transmitted HIV infection in Finland,
      calculated with the incidence/window period model, is approximately 1:3,300,000.
      The calculated risk for hepatitis B (HBV) and C (HCV) is 1:217,000 and 1:147,000
      donations, respectively. In bone banking we can further reduce the risks by
      retesting the living donors. Retesting 2 months after donation seems to be
      sufficient, at least in countries with a low incidence of transplantation
      transmitted infections.

PMID- 9930099
TI  - Function of the rabbit supraspinatus muscle after detachment of its tendon from
      the greater tubercle. Observations up to 6 months.
AB  - The supraspinatus tendon was detached from the greater tubercle in 30 rabbits.
      After 6 weeks (group A), 3 months (group B) and 6 months (group C) in vivo
      evaluation of the twitch-tension and fatigue index were done. Next the scapulas
      with muscles were examined by CT. During the first 6 weeks a marked reduction in
      power and fatigue index by about 20% and 10-15%, respectively, in comparison with
      the control side was noted. These findings remained unchanged at 3 and 6 months.
      The CT examination showed fatty muscle degeneration, mainly in the 1/3 distal
      part of supraspinatus, but not in the infraspinatus muscle.

PMID- 9930100
TI  - Electromyographic activities of the biceps during arm elevation in shoulders with
      rotator cuff tears.
AB  - We investigated electromyographic activities of the biceps in 40 shoulders with
      full-thickness tears of the rotator cuff and 40 asymptomatic shoulders, with a
      normal rotator cuff on MRI, to determine the role of the biceps in cuff-deficient
      shoulders. Using surface electrodes, biceps activities were recorded during arm
      elevation in the scapular plane with and without a 1-kg load. The percentages of
      integrated electromyograms to the maximum voluntary contraction (%MVC) were
      obtained at 30 degrees, 60 degrees, 90 degrees, and 120 degrees of elevation. In
      the normal shoulders, %MVC of the biceps was always less than 10% through the arc
      of elevation both with and without load. Among 40 shoulders with rotator cuff
      tears, 14 showed increased activities of the biceps more than 10% in %MVC (p <
      0.0001), whereas the remaining 26 shoulders had activities similar to the normal
      shoulders. The biceps activities in these 14 shoulders increased with load
      application and at higher angles of elevation. The muscle strength tended to be
      weaker in shoulders with increased biceps activities than in those without. Our
      findings suggest a potential supplemental function of the biceps in shoulders
      with rotator cuff tears.

PMID- 9930101
TI  - Intramedullary versus extramedullary fixation of subtrochanteric fractures. A
      biomechanical study.
AB  - We compared two different subtrochanteric fracture fixation techniques, an
      intramedullary hip screw system (IMHS) and an extramedullary, dual sliding screw
      plate system (MSP), to determine relative fixation stability. 6 matched pairs of
      osteosynthesized osteopenic cadaver femurs were axially loaded to 1000 N with
      concurrent, simulated abductor forces of 0%, 50%, or 86% of the applied head
      force. The initial loading sequence was made with uniaxial dynamization--the lag
      screw of the MSP locked and distal locking of the IMHS nail. Femoral head
      displacement and medial femoral strain were measured for intact femur controls,
      after fixation of a 2-part reverse oblique subtrochanteric fracture and finally a
      3-part reverse oblique subtrochanteric fracture with a lateral wedge defect. The
      samples were then loaded at 750 N for 10(4) cycles with both devices uniaxially
      locked, followed by 10(4) cycles with both devices fully biaxially dynamized
      (unlocked). For the 2-part subtrochanteric fracture pattern, both devices
      exhibited similar inferior displacements of the femoral head (average 2.0 mm) and
      medial femoral strain (approximately 70% of intact). Increasing abductor forces
      decreased medial compressive strain but did not significantly affect head
      displacement. For the 3-part fracture model, the MSP demonstrated significantly
      less inferior displacement of the head (1.6 mm vs. 2.1 mm) and both devices
      demonstrated significantly decreased medial strain. After cycling, head
      displacement increased approximately 50% in both devices and medial strain
      increased slightly. After unlocking and cycling, the MSP group showed significant
      lateral displacement of the proximal fragment. The IMHS and MSP devices provide
      similar stability for fixation of 2-part and 3-part reverse oblique
      subtrochanteric fractures. In a biaxially dynamized, 3-part reverse oblique
      fracture, displacement of the proximal fragment can occur with the MSP.

PMID- 9930102
TI  - Three-dimensional displacement of the hip joint after triple pelvic osteotomy. A
      postmortem radiostereometric study.
AB  - Triple pelvic osteotomy reorients the acetabulum relative to the pelvis in order
      to improve acetabular coverage of the femoral head in cases of acetabular
      dysplasia. We undertook a radiostereometric analysis (RSA) on 6 osteotomized
      cadaver hips to determine the actual three-dimensional reorientation obtained.
      The centers of the femoral head were all translated posteriorly between 11 and 41
      mm, and distally up to 13 mm. 4 were lateralized up to 8 mm, and 2 were
      medialized up to 5 mm. All acetabuli rotated anteriorly about the lateral to
      medial axis (X-axis), and 4 rotated outwards around the distal to proximal axis
      (Y-axis). The correlations between measurements performed on conventional
      anteroposterior radiographs and the RSA measurements were poor: variations in the
      lateral-medial direction ranged from -16 to +6 mm, and in the distal-proximal
      direction between -10 and +12 mm. The changes in orientations measured will
      significantly affect the load across the hip joint, since the dimensions of the
      pelvis change and the moment arms of the muscles, their lengths and lines of
      action are changed as well. We conclude that, with the procedures presently
      performed, the loads across the hip joint are bound to change, and that the
      reorientation can hardly be checked with conventional radiographs.

PMID- 9930103
TI  - Function after anterior cruciate ligament injuries. Influence of visual control
      and proprioception.
AB  - Information about limb positions and movements consists of input from visual,
      vestibular, cutaneous, muscular, tendinous and joint receptors, but the relative
      contribution from each type and location of receptors is not known. The aim of
      this study was: a) to measure the contribution from visual control on extremity
      function, as measured with a one-leg hop test in healthy persons, in patients
      with an asymptomatic ACL injury, after non-operative treatment and in patients
      with a stable knee after an ACL reconstruction, b) to investigate if there was
      any relation between proprioception from the extremity, as measured with the
      threshold for detecting passive motion of the knee, and the one-leg hop test with
      a gradual decrease in visual control. There was a decrease in hop-length when the
      subjects were deprived of visual control that was significant when the dominant
      eye or both eyes were blinded, both in the 2 patient groups and the reference
      population. The magnitude of the length reduction did not differ between the
      groups or between injured and healthy limbs. In all 4 threshold tests performed
      as a measure of peripheral proprioception, a stronger relation to hop-length was
      recorded for the blinded hop than with full visual control in the patients with
      nonoperated ACL injuries. The coefficients of correlation between hop-length and
      the proprioceptive recordings in the injured limb were of the same magnitude as
      on the healthy side.

PMID- 9930104
TI  - Osteochondritis dissecans of the femoral condyle treated with periosteal
      transplantation. Poor outcome in 14 patients followed for 6-9 years.
AB  - We evaluated 14 consecutive periosteal transplantations to treat osteochondritis
      dissecans lesions of the femoral condyle. 1 year postoperatively, 9 knees were
      pain-free, but with 6-9 years follow-up, only 2 knees were pain-free. Formation
      of hyaline-like cartilage, assessed in 12 knees, was documented in 1 patients and
      assessed as possible in 1 more, but in 10 patients the tissue formed in the
      defects was not or probably not hyaline cartilage. 6 knees had developed
      arthrosis.

PMID- 9930105
TI  - MRI evaluation of steroid- or alcohol-related osteonecrosis of the femoral
      condyle.
AB  - We reviewed 30 patients (46 knees) with steroid- or alcohol-related osteonecrosis
      of the femoral condyle. Their average age was 35 (14-61) years and the mean
      observation time was 7 (3-16) years. The medio-lateral extent and the anterior
      posterior (AP) location of the necrotic lesion were evaluated on T1-weighted MRI
      and related to the collapse of the condyle. The size of the lesion was classified
      into three categories on the mid-coronal MRI of the femoral condyle: there were
      44 small, 20 medium, and 9 large lesions. The condyle was divided into 3 zones:
      anterior, middle, and posterior. The location of the lesion was evaluated on the
      mid-sagittal image. There were 7 anterior, 9 middle, 29 posterior, 14 middle and
      posterior and, in 14 cases, all 3 zones were involved. 44 small lesions did not
      collapse, while 6/20 medium lesions and 5/9 large lesions collapsed. No lesion
      involving only one zone collapsed, while 4/14 lesions involving the middle and
      posterior zones and 7/14 lesions involving all three zones progressed to
      collapse. 4/6 condyles with large necrotic lesions involving all three zones
      collapsed. We conclude that the extent of the necrotic lesion on both the mid
      coronal and mid-sagittal planes is of importance for the prognosis of
      osteonecrosis of the femoral condyle.

PMID- 9930106
TI  - Cost of prostheses in patients with unilateral transtibial amputation for
      vascular disease. A population-based follow-up during 8 years of 112 patients.
AB  - We analyzed the cost of prostheses for patients amputated because of vascular
      disease. During 1 year, 112 patients were treated with a primary unilateral
      transtibial amputation in Malmohus county, Sweden, which has 527,000 inhabitants.
      During the first 6 months after the amputation, 50% (56/112) of the patients had
      received a prosthesis. At 6 months, 49 patients (7 had died) were examined, 18
      had poor and 31 had good prosthetic function. Within 1 year, 71 (63%) patients
      had been fitted with a prosthesis. During 8 years after the amputation, they
      received altogether 137 prostheses and 54 exchange sockets; 59% of the prostheses
      and 26% of the sockets were delivered during the first year. Each patient
      received a median of 1 prosthesis and 1 extra socket. During the 8-year period,
      the total cost of prostheses, sockets and maintenance for the 71 patients was USD
      228,746, representing a median cost of USD 1,582 per patient. The total cost of
      maintenance of the prostheses during the same period was USD 37,959, representing
      20% of the total cost of all the prostheses and sockets. There was no
      statistically significant difference in the costs between patients with good or
      poor function.

PMID- 9930107
TI  - Posterior tibial tendon transfer for drop-foot. 20 cases followed for 1-5 years.
AB  - From 1991 to 1997 we performed 20 tibialis posterior tendon-transfer operations
      in 17 patients with drop-foot, in 11 of peripheral neurogenic origin and in 6
      because of neuromuscular disease. Postoperatively, all patients could walk
      without an ankle-foot orthosis. At follow-up after mean 2 (1-5) years, all
      patients had active dorsiflexion of the foot and toes, with a median active ankle
      dorsiflexion of 5 degrees (-15-10 degrees). The median active plantar flexion was
      40 degrees (10-45 degrees), and the total range of movement was 40 degrees (15-50
      degrees). At follow-up, the gait was good in 15 and improved in 2 of the 17
      patients.

PMID- 9930108
TI  - Evaluation of the effect of preoperative chemotherapy in bone sarcomas. 99mTc
      HMDP scintigraphy in 34 cases.
AB  - We quantitatively analyzed images of 99mTc-HMDP bone scintigraphy in 34 bone
      sarcomas before and after preoperative chemotherapy. The isotopic uptake was
      calculated as tumor-to-background ratio (TBR), and the changes in TBR before and
      after chemotherapy were calculated as the alteration ratio. The histological
      effect of preoperative chemotherapy was classified in 4 grades, according to
      Huvos. We defined good scintigraphic responders as cases having decreased uptake
      after chemotherapy, with an alteration ratio > or = 60%. There was a positive
      correlation (Rho = 0.76, p < 0.001) between the histological effect and the
      alteration ratio. Of the 17 good histological responders, 13 showed a good
      scintigraphic response. The average alteration ratio in 17 cases with good
      response (68%) was higher than that in 17 cases showing poor response (-9.9%) (p
      < 0.001). 3 patients with pathologic fractures and 1 with primarily normal uptake
      showed false negative findings. The sensitivity of this method was 100% and the
      specificity was 81%.

PMID- 9930109
TI  - Resection hip arthroplasty for malignant pelvic tumor. Outcome in 5 patients
      followed more than 2 years.
AB  - We describe the technique and outcome of resection hip arthroplasty with external
      fixator for malignant pelvic tumors involving the innominate bone. We used the
      procedure in 5 patients, all followed for more than 2 years. 4 of the patients
      are alive and 1 died of pulmonary metastasis. None of the patients experienced
      local tumor recurrence or infection. Lower limb function in 3 of the 5 patients
      was more than 70% with Enneking's criteria (Enneking et al. 1993). These 3
      patients could walk without support and passively flex the hip up to 90 degrees.
      This resection hip arthroplasty allows early weight bearing with hip motion. We
      believe it is an excellent alternative to other procedures, such as
      endoprosthetic replacement, reconstruction with allograft or arthrodesis.

PMID- 9930110
TI  - OP-1 has more effect than mechanical signals in the control of tissue
      differentiation in healing rat tendons.
AB  - Although osteogenic protein 1 (OP-1) is best known for its ability to induce bone
      formation, it is a differentiation factor with diverse functions in the
      development of non-bony tissues. It is expressed in developing tendon. We
      therefore hypothesized that OP-1 might stimulate the differentiation of a tendon
      callus. Rat achilles tendons were transected and a collagen sponge with or
      without OP-1 was placed in the defect. OP-1 induced the formation of an ossicle,
      which reduced tendon strength at 2 weeks postoperatively. Abolition of muscle
      force by tibial nerve transection or reducing load by forefoot amputation reduced
      tendon strength by almost half during the same period. Thus, traction forces are
      potent tendon-tissue inducers. OP-1 reduced the strength of denervated tendons
      even further, but the induced ossicles appeared similar to those in loaded
      tendons. Thus, both OP-1 and unloading independently reduced tendon strength. In
      conclusion, the ability of OP-1 to induce bone was greater that the mechanical
      and environmental signals for a more traction-resistant tissue, indicating that
      signal proteins may have more direct or stronger effects than mechanical stimuli
      on tissue differentiation. We also found that a single percutaneous injection of
      OP-1 reproducibly induced large amounts of bone in this setting, although it is
      generally believed that BMPs always need to be inserted with a carrier.

PMID- 9930111
TI  - Subchondral bone remodeling increases in early experimental osteoarthrosis in
      young beagle dogs.
AB  - We evaluated subchondral bone remodeling and structure in the condyles of the
      femur and the patellar surface of the femur in early experimental osteoarthrosis
      of young female beagle dogs. 14 littermate (twin) dogs were divided into
      operation (n 7) and control groups (n 7). The dogs in the operation group
      underwent surgically a 30 degrees valgus angulation of the right tibia to induce
      osteoarthrotic articular cartilage lesions in the knee (stifle) joint. 7 months
      postoperatively, bone samples were harvested from both condyles and the patellar
      surface of the femur and evaluated by histomorphometry of subchondral bone.
      Cartilage samples from the same areas were taken for histology. In the operated
      dogs, subchondral bone remodeling increased strikingly in the patellar surface of
      the femur; osteoid thickness and osteoblast surface/bone surface increased up to
      42% and 94% (p < 0.05), as compared to controls. Total and active erosion depths
      increased by 14% and 30% in the same area (p < 0.05). However, in bone structural
      parameters no significant difference could be observed between the groups. In the
      medial condyle of the femur, the trabecular number decreased in operated dogs, as
      compared to controls (p < 0.05). The lateral condyle of the femur in operated
      animals did not differ from controls in the parameters tested. In the operated
      dogs, histology from cartilage samples showed initial osteoarthrotic changes in
      the patellar surface and the medial condyle of the femur. Histologic changes were
      greatest in the patellar surface of the femur, as assessed by the Mankin scores.
      At the very onset of osteoarthrosis, subchondral bone remodeling increases, but
      the bone structural changes are indistinct. It seems that in this osteoarthrosis
      model, cartilage lesions precede major subchondral changes in the structure of
      the bone.

PMID- 9930112
TI  - Protective effect of anisodamine on reperfusion injury of skeletal muscles in
      rabbit.
AB  - Anisodamine is an alkaloid isolated from a Chinese plant, which was subsequently
      synthesized. Its chemical structure is similar to atropine. It inhibits
      cholinergic nerve function, improves microcirculation, and was reported to have a
      protective effect on reperfusion injury in various organs. We used anisodamine in
      a rabbit model with ischemia and reperfusion injury of hind limb muscles. We
      evaluated its effect on skeletal muscle cells, using transmission electron
      microscopy, and analyzed lipid peroxidation by measuring malondialdehyde and
      lactate dehydrogenase blood concentrations. We found that malondialdehyde and
      lactate dehydrogenase concentrations after 1 hour of reperfusion were lower in
      animals treated with anisodamine than in controls. Damage to membrane structures
      and myofilaments in muscle cells was less severe after anisodamine treatment. Our
      findings indicate that anisodamine protects skeletal muscles with ischemia and
      reperfusion injury.

PMID- 9930113
TI  - How to remove a bent intramedullary nail. A technical note.

PMID- 9930114
TI  - Synovial chondromatosis presenting as a pathological fracture of the femoral neck
      in an 89-year-old woman--a case report.

PMID- 9930115
TI  - A report on 2 cases of myositis ossificans in childhood.

PMID- 9930116
TI  - Pseudarthrosis of the spine of the scapula--case report of a minimally invasive
      osteosynthesis technique.

PMID- 9930117
TI  - Sclerotic hip medullary lesion evolving into a simple bone cyst--a case report.

PMID- 9930118
TI  - Synovial chondromatosis associated with osteopoikilosis--a case report.

PMID- 9930119
TI  - Slow-onset subdural hematoma, evolving into paraplegia, after attempted spinal
      anesthesia--a case report.

PMID- 9930120
TI  - Ultrasonography for evaluation of hip dysplasia. Methods and policy in neonates,
      infants, and older children.

PMID- 9930121
TI  - Thromboembolic complications after arthroscopic knee surgery.

PMID- 9930122
TI  - Flexible sigmoidoscopy: the unkept promise of cancer prevention.

PMID- 9930123
TI  - Hepatitis C: who should we be treating?

PMID- 9930124
TI  - Nonsurgical treatment of pain in lumbar spine stenosis.

PMID- 9930125
TI  - Over-the-counter melatonin products and contamination.

PMID- 9930126
TI  - Flexible sigmoidoscopy: screening for colorectal cancer.
AB  - Flexible sigmoidoscopy is an important screening procedure because of its ability
      to detect early changes in the distal colon. The 60-cm flexible sigmoidoscope
      provides excellent visualization with minimal discomfort to patients. Successful
      sigmoidoscopy requires adequate patient preparation, proper equipment and an
      experienced examiner who can recognize both normal and abnormal findings.
      Complications arising from sigmoidoscopy are rare, but patients may experience
      some cramping, gas or watery stools. Screening and primary preventive measures,
      including regular exercise and increased dietary fiber intake, can lower the
      morbidity and mortality associated with colorectal cancer.

PMID- 9930127
TI  - Cervical spine radiographs in the trauma patient.
AB  - Significant cervical spine injury is very unlikely in a case of trauma if the
      patient has normal mental status (including no drug or alcohol use) and no neck
      pain, no tenderness on neck palpation, no neurologic signs or symptoms referable
      to the neck (such as numbness or weakness in the extremities), no other
      distracting injury and no history of loss of consciousness. Views required to
      radiographically exclude a cervical spine fracture include a posteroanterior
      view, a lateral view and an odontoid view. The lateral view must include all
      seven cervical vertebrae as well as the C7-T1 interspace, allowing visualization
      of the alignment of C7 and T1. The most common reason for a missed cervical spine
      injury is a cervical spine radiographic series that is technically inadequate.
      The "SCIWORA" syndrome (spinal cord injury without radiographic abnormality) is
      common in children. Once an injury to the spinal cord is diagnosed,
      methylprednisolone should be administered as soon as possible in an attempt to
      limit neurologic injury.

PMID- 9930128
TI  - Hepatitis C: Part II. Prevention counseling and medical evaluation.
AB  - An estimated 3.9 million Americans are infected with hepatitis C virus (HCV), and
      most do not know that they are infected. This group includes persons who are at
      risk for HCV-associated chronic liver disease and who also serve as reservoirs
      for transmission of HCV to others. Because there is no vaccine to prevent HCV
      infection and immune globulin is not effective for postexposure prophylaxis,
      prevention of HCV infection is paramount. Patients who are at risk of exposure to
      HCV should be advised on steps they might take to minimize their risk of
      infection. Patients who are infected with HCV should be counseled on ways to
      prevent transmission of HCV to others and to avoid hepatotoxins. They should also
      be examined for liver disease and referred for treatment, if indicated.

PMID- 9930129
TI  - Alcohol-related problems: recognition and intervention.
AB  - Early identification of alcohol-related problems is important because these
      problems are prevalent, pose serious health risks to patients and their families,
      and are amenable to intervention. Physicians may be able to help patients change
      their drinking behaviors. The most effective tool for screening is a thorough
      history of the patient's drinking behavior, designed to identify patterns of
      alcohol-related difficulties with physical and mental health, family life, legal
      authorities and employment. Alcohol drinkers can be categorized as at-risk,
      problem or alcohol dependent, according to a protocol developed by the National
      Institute on Alcohol Abuse and Alcoholism. The severity of the alcohol problem
      and the patient's readiness to change should determine the intervention selected
      by the family physician.

PMID- 9930130
TI  - Primary care of infants and young children with Down syndrome.
AB  - Down syndrome is caused by triplicate material of chromosome 21. The syndrome has
      a variable physical expression, but congenital cardiac defects, transient
      myelodysplasia of the newborn and duodenal atresia are highly specific for this
      chromosomal disorder. Routine health maintenance is important because infants and
      children with Down syndrome are more likely to have otitis media, thyroid
      disease, congenital cataracts, leukemoid reactions, dental problems and feeding
      difficulties. Since infants with this syndrome are prone to respiratory
      infections, immunization recommendations should be followed closely. Motor,
      language, social and adaptive skills should be assessed at each office visit. The
      psychosocial aspects of care should be discussed with the parents of an infant
      with Down syndrome. If necessary, the parents should be referred to family
      support and specialty resources. Institutionalization of infants with Down
      syndrome is now unlikely. With newer surgical techniques, early therapy to
      minimize developmental delay and proper health supervision, the functional
      prognosis for infants with Down syndrome is considerably improved.

PMID- 9930131
TI  - Ordering and understanding the exercise stress test.
AB  - The exercise stress test is a useful screening tool for the detection of
      significant coronary artery disease. Documentation of the patient's symptoms,
      medications, past and current significant illnesses, and usual level of physical
      activity helps the physician determine if an exercise stress test is appropriate.
      The physical examination must include consideration of the patient's ability to
      walk and exercise, along with any signs of acute or serious disease that may
      affect the test results or the patient's ability to perform the test. The test
      report contains comments about the maximal heart rate and level of exercise
      achieved, and symptoms, arrhythmias, electrocardiographic changes and vital signs
      during exercise. This report allows the clinician to determine if the test was
      "maximal" or "submaximal." The quality of the test and its performance add to the
      validity of the results. The conclusion section of the test report indicates
      whether the test results were "positive," "negative," "equivocal" or
      "uninterpretable." Further testing may be indicated to obtain optional
      information about coronary artery disease and ischemic risk if the test results
      were equivocal or uninterpretable.

PMID- 9930133
TI  - ACSM revises guidelines for exercise to maintain fitness.

PMID- 9930132
TI  - Manifestations of food allergy: evaluation and management.
AB  - The term "food allergy" refers to adverse immunologic reactions to food. Food
      allergy is usually mediated by IgE antibody directed to specific food proteins,
      but other immunologic mechanisms can also play a role. The primary target organs
      for food allergic reactions are the skin, the gastrointestinal tract and the
      respiratory system. Both acute reactions (hives and anaphylaxis) and chronic
      disease (asthma, atopic dermatitis and gastrointestinal disorders) may be caused
      or exacerbated by food allergy. The foods most commonly causing these reactions
      in children are milk, egg, peanuts, soy, wheat, tree nuts, fish and shellfish; in
      adults, they are peanuts, tree nuts, shellfish and fish. The diagnosis of food
      allergy requires a careful search for possible causes, confirmation of the
      cause(s) with supporting tests, including specific tests for IgE (i.e., prick
      skin tests, radioallergosorbent tests) and, in some cases, oral food challenges.
      Treatment consists of elimination of the causal food(s) along with medical
      treatment, including the prompt self-administration of epinephrine in the event
      of a serious reaction.

PMID- 9930134
TI  - ACOG urges a cautious approach to vaginal birth after cesarean delivery.

PMID- 9930135
TI  - A mentor-based laboratory management elective for residents.
AB  - With the evolution of health care delivery systems, laboratories are being viewed
      as cost centers, and their value is being continually challenged. This requires
      pathologists to be adequately trained as leaders and managers. New training
      curricula for pathology residents have been developed, including combined
      didactic and mentor-based training. At the University of Utah, Salt Lake City,
      the combination of a large academic pathology department with a wholly owned
      commercial laboratory has allowed the development of a comprehensive 1-month
      didactic management course for senior residents. This course is designed to
      develop a broad-based foundation in laboratory management principles. The
      reinforcement of many of these principles, however, requires additional hands-on
      effort. We describe our first experience with this 1-month, theory based-teaching
      followed by a 3-month "real-world" experience based on a one-on-one mentor
      relationship between the director of laboratories and a senior resident, who
      assumed the role of the assistant director of laboratories.

PMID- 9930136
TI  - Current practices in clinical flow cytometry. A practice survey by the American
      Society of Clinical Pathologists.
AB  - The American Society of Clinical Pathologists surveyed 136 laboratories actively
      engaged in performing clinical flow cytometric testing to determine the
      demographics of these laboratories, the credentials of the personnel involved
      with testing, the volume and types of tests performed, and how data are analyzed
      and interpreted. These results are reported with commentary based on previous
      surveys and recommended practice guidelines.

PMID- 9930137
TI  - Lymphoma presenting as a solitary bone lesion.
AB  - Primary lymphoma of bone has characteristic clinical and radiologic
      manifestations; however, its histologic features and clinical outcome show
      considerable variability. The histologic and immunophenotypic features of 13
      adult patients with lymphoma as a solitary bone lesion were compared with
      clinical outcome. All tumors studied were non-Hodgkin lymphoma of anaplastic or
      large cell type and included B-cell (9 cases), T-cell (3 cases), and null cell (1
      case) phenotypes. All patients responded well initially to systemic chemotherapy
      (with or without radiotherapy); however, disease in 6 patients progressed or
      recurred, and 5 patients died of disease. Local disease progression was seen in 2
      patients, with 4 patients experiencing relapse at distant sites. Expression of
      CD30, present in 7 cases, was associated with an anaplastic or large noncleaved
      histologic appearance. Absence of CD30 expression characterized 6 cases,
      including 4 with multilobate or cleaved morphologic features. Five of 6 cases
      that recurred were associated with CD30 expression, including 3 with anaplastic
      features. The 4 tumors with cleaved or multilobate nuclear morphologic features
      were associated with long disease-free survivals and may represent a distinct
      lymphoma subtype with a good prognosis.

PMID- 9930138
TI  - How reliable is histologic examination of bone marrow trephine biopsy specimens
      for the staging of non-Hodgkin lymphoma? A study of hairy cell leukemia and
      mantle cell lymphoma involvement of the bone marrow trephine specimen by
      histologic, immunohistochemical, and polymerase chain reaction techniques.
AB  - Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy
      specimens by morphologic features and immunohistochemistry is often difficult,
      and the criteria for involvement are ill defined. We compared the morphologic and
      immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy
      chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR)
      amplification of the complementarity determining region 3 (CDR3) in bone marrow
      biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell
      leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens
      were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed
      clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal
      IgH rearrangements were present in 61 negative specimens. The 1 false-positive
      and most false-negative PCR results were likely due to sampling error or DNA
      degradation of the fixed tissues. In most cases, bone marrow involvement by NHL
      can be identified by histologic and immunohistochemical examination. Furthermore,
      clonality of the B-cell population can be detected by amplification of the IgH
      CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be
      helpful in cases diagnosed as inconclusive.

PMID- 9930139
TI  - Low megakaryocyte ploidy in Ph-positive chronic myelogenous leukemia measured by
      flow cytometry.
AB  - In chronic myeloproliferative disorders, the megakaryocytes differ in size and
      maturation compared with those of healthy individuals. In the present study, by
      using a 2-color flow cytometry technique, we determined the frequency of bone
      marrow megakaryocytes in different ploidy classes in 13 newly diagnosed and
      untreated patients with Philadelphia chromosome (Ph)-positive chronic myelogenous
      leukemia (CML) and in 12 healthy volunteers. The results showed a significant
      difference in megakaryocyte ploidy distributions between these 2 study groups. On
      the average, patients with CML had 59% of their megakaryocytes in ploidy classes
      2N to 8N; in contrast, the healthy volunteers had only 22% of their
      megakaryocytes in classes 2N to 8N. Two patients with complex Ph translocation
      and 2 patients with a small clone with a chromosome abnormality in addition to Ph
      had the same ploidy distribution as those with only Ph translocation. The
      platelet count did not correlate with the megakaryocyte mean ploidy.

PMID- 9930140
TI  - Calculation vs calibration curve for INR determination. Results of an
      interlaboratory proficiency scheme.
AB  - We surveyed 271 laboratories participating in a quality assessment program to
      ascertain whether the use of a calibration curve for determining the
      international normalized ratio (INR) would improve interlaboratory accuracy and
      precision. Lyophilized warfarinized samples with INR values assigned through
      manual calibration against internationally assigned rabbit reference
      thromboplasts were assayed for prothrombin time. Calibration analysis on the
      results was performed by linear regression. In all but 1 sample, the mean INR
      value computed by the calibration method was closer to the "true" value than the
      mean for the conventional calculation method using the International Sensitivity
      Index (ISI); the ISI calculation consistently overestimated the true value.
      Interlaboratory variation decreased using the calibration method. Variation from
      reagent to reagent was greater than from instrument to instrument, but was
      reduced by the calibration method. The specificity of the ISI for instrument type
      did not seem to alter the findings. Use of in-house calibrators to verify the ISI
      improved precision but not necessarily accuracy. The formation of a stable
      calibration line is consistent over time, but further studies are required to
      confirm whether such calibration improves the accuracy and precision of INR
      determination in practice.

PMID- 9930141
TI  - Intravascular hemolysis secondary to ABO incompatible platelet products. An
      underrecognized transfusion reaction.
AB  - Transfusion of ABO-incompatible platelets to a cardiac surgery patients resulted
      in acute intravascular hemolysis complicated by ventricular tachycardia. Nine
      similar cases with significant morbidity or mortality have been reported in
      similar settings. Five fatalities caused by transfusion of ABO-incompatible
      platelet products have been reported to the US Food and Drug Administration
      during the last 4 years. Non-group O patients, particularly those with small
      plasma volumes, receiving multiple non-group specific platelets in a short time
      are at risk for intravascular hemolysis caused by passively infused anti-A1 or
      anti-B. To prevent intravascular hemolysis in such at-risk patients, the
      indications for platelet transfusion must be continually assessed. If transfusion
      of ABO-incompatible platelet products is necessary, consideration should be given
      to minimizing the accompanying plasma via further concentration of the platelets
      or by saline washing of platelet products.

PMID- 9930142
TI  - Pathologic findings in pregnancies with unexplained increases in midtrimester
      maternal serum human chorionic gonadotropin levels.
AB  - Second trimester maternal serum human chorionic gonadotropin (MShCG) levels are
      commonly obtained as part of a screening protocol for chromosomal anomalies.
      Approximately 4% to 6% of patients have elevated hCG levels for gestational age,
      and this test has been reported to identify a group at risk for pregnancy
      complications. We ascertained 24 patients with unexplained elevated MShCG levels
      and available placental pathology among 5,790 deliveries during a 58-week period
      and compared them with 48 controls with normal MShCG levels delivering during the
      same period. Cases had a higher prevalence of preeclampsia, intrauterine growth
      retardation, and preterm delivery. Pathology in cases included more large-for
      gestational-age placentas, fewer small-for-gestational-age placentas, lower mean
      fetoplacental weight ratios, more decidual plasma cell infiltrates, and more
      retroplacental hematomas. Other more frequent abnormalities that did not reach
      statistical significance included abnormal placental shape and chronic villitis.
      Maternal and fetal vascular abnormalities were similar in both groups.
      Morphometric analysis were performed on hCG-immunostained sections from placentas
      at 17, 21, 36, and 41 weeks' gestation. Patients with elevated MShCG showed an
      increased volume of hCG-positive trophoblast per unit surface area and increased
      intensity of hCG immunoreactivity within individual terminal villous units.

PMID- 9930143
TI  - Follicular variant of papillary carcinoma. Cytologic and histologic correlation.
AB  - The cytologic diagnosis of follicular variant of papillary thyroid carcinoma
      (FVPTC) can be difficult owing to the paucity of nuclear changes of papillary
      carcinoma and overlapping features with other follicular-derived lesions. We
      report our fine-needle aspiration (FNA) experience with 17 histologically proved
      cases of FVPTC with a preceding FNA. All cases showed increased cellularity and a
      background of moderate to abundant thin watery colloid with variable amounts of
      thick eosinophilic colloid. The cells were arranged mainly in monolayer sheets
      and syncytial fragments; occasional microfollicle formation with abundant fine
      eosinophilic cytoplasm was seen. Nuclear enlargement was a consistent finding in
      all cases. Only 5 cases showed prominent nuclear features of papillary carcinoma.
      Histologic examination showed encapsulated follicular-patterned nodules with
      multifocal random distribution of nuclear features of papillary carcinoma that
      were more pronounced in the subcapsular locations of the lesions. This
      morphologic heterogeneity explains the variability seen in FNA specimens of FVPTC
      and may result in false-negative diagnoses. We believe that these findings should
      be considered when interpreting follicular lesions; suspicion of an FVPTC should
      be conveyed in the cytopathology report, which may prompt intraoperative
      assessment to avoid a second surgical intervention for completion thyroidectomy.

PMID- 9930144
TI  - Perineural invasion in prostate needle biopsy specimens. Correlation with
      extraprostatic extension at resection.
AB  - The significance of perineural invasion in prostate needle biopsy specimens for
      predicting extraprostatic extension is controversial. We correlated the presence
      of perineural invasion in needle biopsy specimens from 340 men with the presence
      of extraprostatic extension in corresponding radical prostatectomy specimens.
      Perineural invasion was present in 57 biopsy specimens. The sensitivity of
      perineural invasion for predicting extraprostatic extension was 32%, the
      specificity 88%, and the positive predictive value 42%. Biopsy specimens with
      perineural invasion had significantly more core specimens involved with tumor and
      higher biopsy-determined Gleason scores than those without invasion. Biopsy
      specimens with perineural invasion were significantly more likely to show
      extraprostatic extension and Gleason scores were higher in the resection
      specimens than those without perineural invasion. Multivariate logistic
      regression analysis showed that perineural invasion remained an independent
      predictor of extraprostatic extension. However, in multivariate analysis,
      including preoperative serum prostate-specific antigen (PSA) for 173 of the
      patients, the only independent predictor of extraprostatic extension was PSA.
      While perineural invasion in biopsy specimens is a predictor of extraprostatic
      extension at resection that is independent of other histologic features, the
      positive predictive value is low and it is not an independent predictor when
      serum PSA is included.

PMID- 9930145
TI  - Inhibin is not an immunohistochemical marker for hepatocellular carcinoma. An
      example of the potential pitfall in diagnostic immunohistochemistry caused by
      endogenous biotin.
AB  - Inhibin is a heterodimeric glycoprotein originally detected in gonadal tissues.
      One report described inhibin immunopositivity in 17 of 19 hepatocellular
      carcinomas (HCCs) and the hepatocytes of the surrounding nonneoplastic
      parenchyma. The reported immunohistochemical method, which used avidin-biotin
      complex, did not describe blocking endogenous biotin. Since liver tissue may
      contain high levels of biotin, endogenous biotin may result in false-positive
      immunostaining. We wondered whether this reported immunopositivity represented a
      false-positive result due to unblocked endogenous biotin. By using a similar
      antigen retrieval technique and the same specificity, titer, and clonal source of
      primary antibody as the aforementioned study, we performed immunostaining for
      inhibin with and without an endogenous biotin blocking step on 23 cases of HCC
      and the surrounding cirrhotic liver. In all cases, the HCC and the hepatocytes in
      the cirrhotic nodules were negative for inhibin when the endogenous biotin
      blocking step was used. When the blocking step was omitted, apparent
      immunostaining was noted in 20 of 23 HCCs and in the hepatocytes in all cases.
      Accordingly, HCC and the hepatocytes of the surrounding cirrhotic liver are
      immunohistochemically negative for inhibin. The previously reported
      immunopositivity of HCC and nontumoral hepatocytes for inhibin represents a false
      positive result due to endogenous biotin.

PMID- 9930146
TI  - Immunoreactivity of a new CD5 antibody with normal epithelium and malignant
      tumors including thymic carcinoma.
AB  - CD5, first recognized on subsets of lymphocytes, also is detected in thymic
      carcinoma but not in thymoma or other malignant tumors. We studied CD5 expression
      in 73 cases of malignant tumors of various organs, 22 cases of thymoma, and 7
      cases of thymic carcinoma by immunohistochemistry using the new monoclonal anti
      CD5 antibody, NCL-CD5-4C7, with a pressure cooker antigen retrieval method. All
      cases of thymic carcinoma showed positive staining for CD5, predominantly on the
      cell membrane. Two of 4 cases of atypical thymoma also showed focal positivity,
      whereas the other types of thymoma were negative. CD5 was detected in cases of
      malignant tumors other than squamous cell carcinoma and in the normal epithelium
      of their counterparts. Squamous cell carcinomas of various organs were negative
      for CD5. Malignant mesothelioma showed peculiar intracytoplasmic staining in
      contrast to the other tumors. The NCL-CD5-4C7 positivity in thymic epithelial
      tumors may support the hypothesis suggesting progression of atypical thymoma to
      thymic carcinoma. NCL-CD5-4C7 may be useful in the differential diagnosis of
      mediastinal tumors, especially between thymic carcinoma and metastatic squamous
      cell carcinoma of various primary sites, and for distinguishing malignant
      mesothelioma from adenocarcinoma of the lung by the different staining pattern.

PMID- 9930147
TI  - Molecular alterations in early gastric carcinomas. No apparent correlation with
      Helicobacter pylori status.
AB  - Data on the differences in molecular profile between H pylori-positive and H
      pylori-negative early gastric carcinomas, if any, are almost nonexistent. We
      therefore investigated whether molecular differences can be observed between H
      pylori-positive and H pylori-negative early gastric carcinomas. Forty-five early
      gastric carcinomas were analyzed for alterations in certain oncogenes (ras, MDM2,
      c-erbB-2, cyclin D1), the p53 tumor suppressor gene, and the e-cadherin gene. Of
      these 28 carcinomas were H pylori-positive, and 17 were H pylori-negative. No
      significant differences were found in the groups irrespective of Lauren type; ras
      (0% vs 0%), MDM2 (0% vs 0%), c-erbB-2 (0% vs 0%), cyclin D1 (18% vs 29%), p53
      (68% vs 47%), and e-cadherin (46% vs 41%). Helicobacter pylori-positive and H
      pylori-negative early gastric carcinomas do not differ in molecular profile.
      Although they may prove different when tested for other abnormalities, our
      findings suggest that the acquisition of molecular alterations occurs via an H
      pylori independent pathway.

PMID- 9930148
TI  - Omental endosalpingiosis with endometrial-type stroma in a woman with extensive
      hemorrhagic pelvic endometriosis.
AB  - A 38-year-old woman with extensive hemorrhagic endometriosis causing back pain,
      pelvic masses, and hydronephrosis also had a palpable omental mass composed of
      abundant endometrial-type stroma in which the epithelial component was entirely
      tubal type glandular cells; the stroma in this area did not bleed. This
      difference in bleeding behavior supports the concept that patterns of
      differentiation of heterotopic mullerian tissues may depend in part on the
      influence of local factors and that endometrial epithelium may produce a local
      trophic or paracrine factor that is absent in tubal epithelium.

PMID- 9930149
TI  - Hepatitis C virus genotypes and quantification of serum hepatitis C RNA in liver
      transplant recipients. Relationship with histologic outcome of recurrent
      hepatitis C.
AB  - The reasons for wide variations in the severity of recurrent hepatitis C after
      liver transplantation are unclear. We studied liver transplant recipients to
      assess the effect of hepatitis C virus (HCV) genotype and HCV RNA quantification
      on histologic progression of recurrent hepatitis C after transplantation. Twenty
      five patients underwent transplantation for HCV cirrhosis and were followed up
      with virologic and histologic assessments for a mean of 51 months. HCV genotype
      was determined by line probe assay. HCV RNA was quantitated in serum samples by
      nested polymerase chain reaction. The HCV genotype 1 was detected in 17 patients
      and other genotypes in 8. Acute lobular hepatitis developed in 17 patients 162
      days posttransplantation on average. Long-term biopsy specimens (mean, 51 months
      after the date of liver transplantation; range, 24-86 months) showed chronic
      hepatitis in 19 patients (mild, 5; moderate, 9; and severe, 5, 2 with extensive
      scarring). The serum alanine aminotransferase level was correlated with
      hepatocyte necrosis (piecemeal and lobular) but not with portal inflammation or
      fibrosis. Patients infected with genotype 1 had a higher Knodell score, and the 5
      patients with severe hepatitis C all were infected with genotype 1. HCV RNA
      levels were significantly higher in patients with genotype 1 than in patients
      with other genotypes, as were the severity of histologic recurrence and levels of
      viral replication.

PMID- 9930150
TI  - The cost-effectiveness of the cytology laboratory and new cytology technologies
      in cervical cancer prevention.
AB  - The effect of changes in cytology laboratory costs, including the costs of new
      technologies, on the cost-effectiveness of cervical cancer prevention has not
      been studied. Using University of Iowa laboratory detection rates and costs, a
      decision model determined the cost-effectiveness of the laboratory with and
      without new technologies. Compared with not performing a cervicovaginal smear,
      the cost to increase the discounted life expectancy per patient by 1 year was
      $2,805 for the laboratory component alone and $19,655 for the entire cervical
      cancer prevention strategy. In moderate- to high-risk women, cervical cancer
      screening was cost-effective even at high cytology laboratory costs (eg, $75 per
      smear). New technologies were cost-effective only if they resulted in a
      substantial increase in the detection of high-grade squamous intraepithelial
      lesions (eg, an additional 236 high-grade squamous intraepithelial lesions per
      10,000 women). New technologies have not demonstrated these increased detection
      rates.

PMID- 9930151
TI  - Nuclear matrix proteins and their potential applications to diagnostic pathology.
AB  - The nuclear matrix is the nonchromatin scaffolding of the cell nucleus that
      confers nuclear shape, organizes the nuclear chromatin, and regulates many
      important intranuclear biochemical events. Although our understanding of the
      nuclear matrix and its proteins is still evolving, it is clear that nuclear
      matrix proteins (NMPs) hold considerable promise as diagnostic tools for
      pathologists. Early evidence suggests that NMPs may be useful biomarkers of
      neoplastic disease in serum, body fluids, and tissues. NMPs are also potential
      candidates for use as tumor prognostic factors and targets of anticancer drugs.
      Moreover, NMPs may hold the key to understanding important cellular events, such
      as neoplastic transformation, steroid hormone binding, and apoptosis. Despite
      impressive gains made by cellular biologists and biochemists toward understanding
      the structure and function of the nuclear matrix, many of the potential
      applications of NMPs to diagnostic pathology are largely unexplored. Thus, NMPs
      should prove an exciting and fruitful area of investigation for experimental and
      clinical pathologists who are interested in developing diagnostic tests for
      detecting, quantitating, and characterizing these proteins in human tissues and
      body fluids and translating these applications into the clinical pathology
      laboratory.

PMID- 9930152
TI  - Autopsies and medical malpractice.

PMID- 9930153
TI  - As good as it gets?

PMID- 9930154
TI  - The autopsy as a research tool.

PMID- 9930155
TI  - Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal
      tension glaucoma.
AB  - OBJECTIVES: To determine the effect of central corneal thickness (CCT) on the
      measurement of intraocular pressure (IOP) and on the resultant reclassification
      of patients as having primary open-angle glaucoma (POAG), normal tension glaucoma
      (NTG), or ocular hypertension (OHT). METHODS: Intraocular pressure (Goldmann
      applanation tonomety) and CCT (ultrasound pachymetry) were measured in 22
      patients with NTG, 49 with POAG, 44 with OHT and in 18 control subjects. The CCT
      was used to obtain a corrected value for the IOP and to reclassify the type of
      glaucoma. RESULTS: There was no significant difference in CCT between controls
      (552 +/- 35 microns) and patients with POAG (543 +/- 35 microns), but the CCT in
      the group with NTG (521 +/- 31 microns) was significantly lower than that in the
      control group or the group with POAG (P < .001), and the CCT in the group with
      OHT (583 +/- 34 microns) was significantly higher than in controls or patients
      with POAG (P < .001). Correcting IOP for corneal thickness, 31% of the patients
      with NTG could be reclassified as having POAG, and 56% of the patients with OHT
      as normal. CONCLUSIONS: Patients with NTG have a thinner CCT than do patients
      with POAG or controls. Underestimation of the IOP in patients with POAG who have
      thin corneas may lead to a misdiagnosis of NTG, while overestimation of the IOP
      in normal subjects who have thick corneas may lead to a misdiagnosis of OHT.

PMID- 9930156
TI  - Bilateral implantation of asymmetrical diffractive multifocal intraocular lenses.
AB  - OBJECTIVE: To evaluate visual results after bilateral implantation of multifocal
      intraocular lenses (IOLs) with asymmetrical light distribution for the far and
      near focus. METHODS: Twenty-nine patients underwent bilateral implantation of
      silicone-optic, foldable, diffractive IOLs in a prospective, 2-center,
      noncontrolled interventional study. Each patient had a distant-dominant
      multifocal IOL implanted in 1 eye and a near-dominant multifocal IOL implanted in
      the fellow eye. Refractive and visual results, including contrast acuity and
      binocular visual function, were determined. Patients were questioned for
      postoperative spectacle usage. RESULTS: Visual and contrast acuity in the
      dominant focus of either lens was superior to that in the nondominant focus at
      3.5 to 12 months postoperatively, i.e., performance was best at distance for the
      distant-dominant and at near for the near-dominant lens. In binocular viewing,
      the monocular maximal results added up to an improved binocular visual
      performance. Binocular visual function was within normal limits. Eighty percent
      of patients reported no use of spectacles at any time postoperatively.
      CONCLUSIONS: Bilateral implantation of asymmetrical diffractive IOLs is an
      effective alternative for restoring simultaneous distance and near vision with a
      potential for improved contrast sensitivity compared with conventional multifocal
      IOLs.

PMID- 9930157
TI  - Comparison of conventional and high-pass resolution perimetry in a prospective
      study of patients with glaucoma and healthy controls.
AB  - OBJECTIVE: To determine whether high-pass resolution perimetry detected
      glaucomatous visual field progression earlier than conventional perimetry.
      METHODS: In a prospective longitudinal study, we observed 113 patients with open
      angle glaucoma and with early to moderate visual field damage and 119 healthy
      control subjects. Each subject underwent testing at 6-month intervals using
      conventional and high-pass resolution perimetry (program 30-2 of the Humphrey
      Field Analyzer [Humphrey Instruments, Inc, San Leandro, Calif] and the Ring
      program of the Ophthimus perimeter [Hi-Tech Vision, Goteborg, Sweden],
      respectively). Our predetermined criterion for progression with conventional
      perimetry was the presence of at least 4 overlapping nonedge locations outside
      the fifth percentile for test-retest variability of threshold deviations (defined
      by the Glaucoma Change Probability Analysis of the Statpac 2 program) in 2 of 3
      consecutive visual fields. We employed the identical criterion for progression
      with high-pass resolution perimetry using our own test-retest variability data.
      We repeated this procedure in the controls to measure the false-positive rate of
      progression. RESULTS: Patients were observed for a median of 4.5 years and 11
      examinations with each technique. Fifty-seven patients (50.4%) did not show
      progression with either technique. Twenty-four patients (21.2%) showed
      progression with high-pass resolution perimetry alone, whereas 6 (5.3%) showed
      progression with conventional perimetry alone. Of the remaining 26 patients
      (23.0%) who showed progression with both techniques, 14 (54%) showed progression
      with high-pass resolution perimetry first (median, 12 months earlier); 5 (19%),
      with conventional perimetry first (median, 6 months earlier); and 7 (27%), with
      both techniques at the same time. Controls were observed for a median of 5 years
      and 11 examinations with each technique. One control (0.8%) showed progression
      with high-pass resolution perimetry. CONCLUSIONS: Our results suggest that high
      pass resolution perimetry detects glaucomatous visual field progression earlier
      than conventional perimetry in most patients with progression.

PMID- 9930158
TI  - Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence
      of angiographic cystoid macular edema in early postoperative pseudophakias.
AB  - OBJECTIVE: To study the effect of latanoprost, a prostaglandin analog, on the
      blood-aqueous barrier and angiographic cystoid macular edema (CME) formation in
      early postoperative pseudophakias. PATIENTS AND METHODS: Included in the study
      were eyes with ocular hypertension, normal-tension glaucoma, or primary open
      angle glaucoma undergoing surgery for cataract. The study consisted of a
      randomized double-masked trial for latanoprost and an open-label controlled trial
      for determining the effects of diclofenac sodium or fluorometholone eyedrop use
      on latanoprost or its placebo. We compared 4 groups of eyes with concurrent
      application of latanoprost and diclofenac (group A), latanoprost and
      fluorometholone (group B), latanoprost placebo and diclofenac (group C), and
      latanoprost placebo and fluorometholone (group D). A laser flare cell meter was
      used to determine the severity of blood-aqueous barrier disruption, and
      fluorescein angiography was performed to determine angiographic CME formation.
      Mean diurnal intraocular pressure differences were compared on the preoperative
      baseline day and in the fifth postoperative week. Latanoprost (0.005%) or its
      placebo was given once a day starting 2 days before surgery until the fifth
      postoperative week. Diclofenac or fluorometholone eyedrops were given 4 times a
      day before surgery on the day of surgery and 3 times a day until the fifth
      postoperative week. RESULTS: In group B compared with group D, the amount of
      flare 3 days and 1 and 2 weeks after surgery and the incidence of angiographic
      CME in the fifth postoperative week were significantly higher. These 2 factors
      were significantly higher in group B than in group A (P < .05) and in group D
      than in group C (P < .01). There was no significant difference in these factors
      between groups A and C. The intraocular pressure decline was significant in
      groups A and B compared with groups C and D (P < .05), but there was no
      significant difference between groups A and B and between groups C and D.
      CONCLUSIONS: Latanoprost therapy enhances disruption of the blood-aqueous barrier
      and increases the incidence of angiographic CME formation in early postoperative
      pseudophakias. Because administration of nonsteroidal eyedrops such as diclofenac
      seems to prevent the adverse effects of latanoprost therapy while maintaining its
      effect to lower intraocular pressure, we suggest their concurrent application.

PMID- 9930159
TI  - Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein
      occlusion.
AB  - OBJECTIVE: To determine whether heritable thrombophilia and hypofibrinolysis were
      risk factors for retinal vein occlusion. DESIGN: Measures of thrombophilia
      (increased likelihood of thrombus formation) included anticardiolipin antibodies
      (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom
      clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain
      reaction assays were performed for 3 thrombophilic gene mutations (factor V
      Leiden, methylenetetra-hydrofolate reductase, and prothrombin gene). Measures of
      hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a),
      plasminogen activator inhibitor activity, and polymerase chain reaction analysis
      of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation
      measures were performed in 17 patients with retinal vein occlusions with
      comparison with serologic coagulation measures and polymerase chain reaction
      assays in 40 and 234 healthy normal volunteers as controls, respectively.
      RESULTS: Of 14 patients with retinal vein occlusion with measures of dilute
      Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6
      (43%) had abnormal results (> 38.8 seconds) compared with 1 (3%) of 30 controls
      (P = .002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the
      thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233
      controls (P = .02). Of 17 patients with vein occlusion, 2 (12%) had normal
      alleles (5G/5G) for the plasminogen activator inhibitor gene promoter; the other
      15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is
      associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G
      allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism (P =
      .03). Patients with vein occlusion were more likely to have high levels of the
      major determinant of hypofibrinolysis, plasminogen activator inhibitor activity.
      These levels were high (> 22 U/L) in 6 (38%) of 16 patients with vein occlusion
      compared with 1 (2%) of 40 controls (chi 2 = 12.8; P = .001). Patients with vein
      occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic
      Lp(a) (> 35 mg/dL) than controls (5/40 [13%]; chi 2 = 9; P = .003). The median
      Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62
      mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype (P = .05).
      CONCLUSION: Thrombophilia and hypofibrinolysis are possible causes of retinal
      vein occlusion.

PMID- 9930160
TI  - Idiopathic reactive hyperplasia of the retinal pigment epithelium.
AB  - OBJECTIVES: To present and discuss 2 patients with acquired peripapillary
      pigmented lesions. METHODS: We reviewed the patients' clinical records and
      histopathologic findings. RESULTS: The first patient was diagnosed with a
      pigmented papillary lesion that was followed up for 38 years. The second patient
      was a child with neurofibromatosis type 1 who developed a pigmented peripapillary
      lesion following excision of an optic nerve glioma. Histologic findings in both
      cases demonstrated hyperplasia of the retinal pigment epithelium with associated
      findings. CONCLUSIONS: The lesions presented an idiopathic reactive hyperplasia
      of the retinal pigment epithelium. The clinical and histopathologic findings
      resemble findings reported with the combined hamartoma. We suggest that such
      lesions are reactive in nature, rather than hamartomatous.

PMID- 9930161
TI  - Sino-orbital aspergillosis in acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To describe the clinical features, causes, imaging characteristics,
      treatment, and outcome of patients with the acquired immunodeficiency syndrome
      (AIDS) and sino-orbital aspergillosis. DESIGN: Records of 5 patients were
      reviewed. Results of imaging and histopathologic examinations and clinical
      courses of the patients were studied. RESULTS: There were 3 women and 2 men (mean
      age, 34.0 years). All had received a diagnosis of AIDS, and mean CD4+ cell count
      was 0.014 x 10(9)/L (14 cells/mm3). Computed tomographic scanning exhibited
      heterogeneous, enhancing sino-orbital soft tissue lesions with bony erosion, and
      magnetic resonance imaging disclosed soft tissue masses hypointense on T1- and T2
      weighted images. The infection involved 1 or more paranasal sinuses, with
      extension into the right orbit in 3 patients and into the left orbit in 2.
      Patients were treated with aggressive surgical debridement and intravenous
      antifungal agents. In addition, local irrigation of amphotericin B was performed
      in 3 patients. Aspergillus fumigatus was found to be the cause in all 5 patients.
      Intracranial extension developed in 4 patients, and all subsequently died. The 2
      longest surviving patients were the only ones being treated with protease
      inhibitors. Three patients had a history of frequent marijuana smoking.
      CONCLUSIONS: Sino-orbital aspergillosis is a progressive, relentless, and usually
      fatal opportunistic infection of advanced AIDS. Patients are first seen with long
      standing headache and proptosis with minimal external inflammatory signs.
      Marijuana smoking may increase the risk for development of sino-orbital
      aspergillosis in these patients. Aggressive surgical and medical treatment,
      combined with newer combination therapies using protease inhibitors, may improve
      the longevity of these patients.

PMID- 9930162
TI  - Immunolocalization of beta ig-h3 protein in 5q31-linked corneal dystrophies and
      normal corneas.
AB  - OBJECTIVE: To characterize the relation of the beta ig-h3 protein to the
      diagnostic corneal deposits in the hereditary corneal dystrophies recently shown
      to have mutations in the beta ig-h3 gene on chromosome 5q31. METHODS: Corneas
      with lattice, granular, mixed granular-lattice ("Avellino"), and 2 types of Reis
      Bucklers dystrophy were diagnosed by the histochemical and ultrastructural
      characteristics of their abnormal aggregates. Dystrophic and normal corneas were
      compared for immunolocalization of beta ig-h3 protein. RESULTS: In normal
      corneas, immunoreactivity for beta ig-h3 protein was strongest in the Bowman
      layer, and next strong along stromal interlamellar junctions and attachment sites
      of collagen to the Descemet membrane. Antibody binding was intense on all
      dystrophic aggregates, mimicking somewhat the normal protein distribution. Mixed
      granular-lattice dystrophy had the most variation in beta ig-h3-immunopositive
      forms. The aggregates in both the "rod-shaped" Reis-Bucklers type and the "curly
      fiber" Thiel-Behnke type were strongly stained for beta ig-h3 protein, consistent
      with mutations on the beta ig-h3 gene. CONCLUSIONS: The marked immunopositivity
      for beta ig-h3 protein in the abnormal deposits in these dystrophies indicates
      that beta ig-h3 protein is a major component. The variety and quantity of
      immunopositive forms suggests that they consist primarily of the mutant protein,
      self-polymerizing and/or incorrectly binding to other corneal components.
      Variability of forms may relate to both the specific mutation and regional
      interactions of this protein.

PMID- 9930164
TI  - A new pressure attenuation index to evaluate retinal circulation. A link to
      protective factors in diabetic retinopathy.
AB  - BACKGROUND: Low ocular perfusion pressure (two thirds of mean arterial pressure
      minus intraocular pressure) and myopia have been associated with protection of
      the retina from clinical diabetic retinopathy. This prompts the question as to
      whether myopia's protective role could also be a pressure effect, given that
      pressure could be dissipated in the longer arteriole tree of the myopic eye.
      METHODS: We combined the Ohm, Poiseuille, and Murray laws to derive the following
      new formulation: the pressure attenuation along a vessel varies directly with its
      length and inversely with its diameter. A mean pressure attenuation index was
      calculated for 22 healthy control subjects, 25 patients with axial myopia, and 6
      patients with retinitis pigmentosa using digitized fundus images. RESULTS: The
      myopic arteriolar tree would produce a 16% greater pressure attenuation than that
      of controls (P = .002), with a linear relationship between mean pressure
      attenuation index and axial length (r = 0.93). Mean pressure attenuation index of
      the group with retinitis pigmentosa is increased 67% above that of controls,
      which is calculated to contribute an additional 10 mm Hg of pressure dissipation
      along their retinal arteriolar system. CONCLUSIONS: Pressure attenuation in
      retinal arterioles is directly proportional to the length and inversely
      proportional to the diameter of the arteriole segment being measured. CLINICAL
      RELEVANCE: A pressure attenuation index may be important in light of the entities
      known or presumed to protect the retina from diabetic retinopathy. The results
      support the hypothesis that low-end arteriolar pressure is a common denominator
      for many protective conditions in diabetic retinopathy.

PMID- 9930163
TI  - Mitotic effect of autologous blood injection and diode laser bleb revision on
      rabbit filtration blebs.
AB  - OBJECTIVE: To investigate the effect of intrableb autologous blood injection and
      diode laser bleb revision on cellular proliferation in filtration blebs of
      rabbits. METHODS: Bilateral filtration surgery with mitomycin was performed on 19
      white 2.5- to 3-kg New Zealand rabbits. Autologous blood injection (n = 9) or
      diode laser bleb revision (n = 10) was performed on blebs of right eyes
      (intervention eyes) on day 14 after filtration surgery. The blebs of the left
      eyes served as controls. Cellular proliferation was assessed by in vivo
      incorporation of 5-bromo-2'-deoxyuridine (BrdU), after BrdU, 10 mg/kg, was
      injected via the ear vein on days 15, 16, and 18. The rabbits were euthanized on
      day 21. Conjunctival sections were stained with hematoxylin-eosin for total cell
      counts and with anti-BrdU antibody for counts of proliferating cells. The BrdU
      labeling index was calculated by dividing the mean proliferating cell count by
      the mean total cell count. RESULTS: The BrdU labeling index was significantly
      increased in the blood-injected eyes as compared with the control eyes (P = .03).
      The BrdU labeling index was increased in the diode laser-revised eyes as compared
      with the control eyes, approaching significance (P = .06). Intraocular pressure
      increased significantly in the eyes that underwent bleb interventions in both
      groups from baseline and compared with the control eyes. CONCLUSIONS: Intrableb
      autologous blood injection and diode laser bleb revision stimulate cellular
      proliferation in the rabbit filtration bleb, which may contribute to the rise in
      intraocular pressure observed clinically after these interventions.

PMID- 9930165
TI  - A novel mutation at codon 124 (R124L) in the BIGH3 gene is associated with a
      superficial variant of granular corneal dystrophy.
AB  - OBJECTIVE: To identify the mutation in a human transforming growth factor beta
      induced gene (BIGH3) in a Japanese family with a severe form of granular corneal
      dystrophy of early onset associated with recurrent corneal erosions. PATIENTS:
      The tentative clinical diagnosis in this family was Reis-Bucklers corneal
      dystrophy; 4 persons affected with this disorder have been identified in 4
      generations, and 3 of the 4 were examined. The proband underwent keratoplasties
      in our hospital (Keio University Hospital, Tokyo, Japan). METHODS: The BIGH3 gene
      was examined for a mutation by the polymerase chain reaction and direct
      sequencing. Corneal buttons of the proband were stained and examined by electron
      microscopy. RESULTS: Three affected persons were shown to have a heterozygous G-
      >T transversion at the second nucleotide position of codon 124 (Arg-->Leu) of the
      BIGH3 gene. In the proband, corneal deposits between the epithelium and the
      Bowman layer stained red with Masson trichrome stain. Electron microscopy
      revealed numerous electron-dense, rod-shaped bodies next to the epithelial
      basement membrane but no curly fibers suggestive of Thiel-Behnke dystrophy.
      CONCLUSION: A novel R124L mutation of the BIGH3 gene was associated in this
      family with a superficial variant of granular corneal dystrophy. CLINICAL
      RELEVANCE: This mutation causes a severe form of superficial granular corneal
      dystrophy by producing abnormal keratoepithelin between the epithelium and the
      Bowman layer and thus clinical similarities to Reis-Bucklers corneal dystrophy.

PMID- 9930166
TI  - Distance and near visual acuity, contrast sensitivity, and visual fields of 10
      year-old children.
AB  - OBJECTIVE: To measure monocular distance visual acuity, near visual acuity,
      contrast sensitivity, and visual field extent in full-term, 10-year-old children
      tested according to the protocol used to test 10-year-old preterm children in the
      Cryotherapy for Retinopathy of Prematurity study. SUBJECTS AND METHODS: Subjects
      were 106 healthy, full-term children, 9.8 to 10.9 years of age, who had no ocular
      abnormalities other than ametropia. All were tested monocularly using Early
      Treatment and Diabetic Retinopathy Study distance and near visual acuity charts
      and Pelli-Robson contrast sensitivity charts, with refractive error corrected
      according to Cryotherapy for Retinopathy of Prematurity study criteria. Goldmann
      perimetry was tested without correction using the V-4-e and III-4-e stimuli along
      8 meridia. A standard pediatric eye examination was performed on each subject.
      RESULTS: Mean (SD) distance visual acuity was 20/19.6 OD (0.082 log unit [lu])
      and mean near visual acuity was 20/19.5 OD (0.100 lu). Mean (SD) contrast
      sensitivity was 1.69 OD (0.12 lu), with a mean (SD) of 36.4 (2.2) letters read.
      Visual field extent was larger for the V-4-e stimulus than for the III-4-e
      stimulus. CONCLUSIONS: The results provide the first monocular normative data
      from a large sample of 10-year-old children tested with Early Treatment and
      Diabetic Retinopathy Study distance and near visual acuity charts and the Pelli
      Robson contrast sensitivity charts, and add to the literature on Goldmann
      perimetry in children.

PMID- 9930167
TI  - Why literacy matters. Links between reading ability and health.
AB  - The ability to understand verbal and written materials is central to modern life.
      Yet, the US Department of Education estimated that 47% of all adult Americans in
      1993 had poor reading and comprehension skills. Analyses of the readability of
      patient education materials, discharge instructions, and consent forms throughout
      many specialties within medicine have found almost uniformly that these materials
      are written at too complex a level for many or most patients. For example, a
      study of the patient ophthalmic education materials of the American Academy of
      Ophthalmology by Ebrahimzadeh et al found large amounts of the material exceeded
      the reading abilities of much of the American adult population. Yet, this is only
      one small part of understanding the effects of literacy and reading abilities on
      our patient's health and their use of our increasingly complex health care
      system.

PMID- 9930168
TI  - Tonometry and corneal thickness.

PMID- 9930169
TI  - Changing policies in the Veterans Health Administration. Will they make a
      difference?

PMID- 9930170
TI  - The best excitement in age-related macular degeneration.

PMID- 9930171
TI  - Lacrimal gland choristoma of the iris.
AB  - Intraocular lacrimal gland tissue is an extremely rare choristoma. A newborn girl
      was seen with a fleshy, vascular tumor arising from the peripheral iris and the
      anterior chamber angle. The tumor was treated with topical steroids on suspicion
      of a juvenile xanthogranuloma; later, it grew slightly and a secondary glaucoma
      developed. Histopathological examination of the resected tumor showed lacrimal
      gland tissue in the iris. Twelve cases of intraocular lacrimal gland tissue have
      been reported in the literature.

PMID- 9930172
TI  - Adenoma of the nonpigmented ciliary epithelium mimicking a malignant melanoma of
      the iris.
AB  - Adenomas of the nonpigmented ciliary epithelium are rare tumors and are difficult
      to differentiate from amelanotic malignant melanomas of the ciliary body. We
      describe a 62-year-old woman with a nonpigmented, vascularized iris tumor with
      small satellites involving the anterior chamber angle. Clinically, an amelanotic,
      tapioca, malignant melanoma of the iris was suggested although the blood-aqueous
      barrier was intact. A block excision of 7.5 mm, a tectonic corneoscleral graft,
      and a simultaneous extracapsular cataract extraction with implantation of a
      posterior chamber lens were performed. Histopathologic and electron microscopic
      studies revealed an adenoma of the nonpigmented ciliary epithelium. Postoperative
      visual acuity was 20/40 OD after 6 weeks. An adenoma of the nonpigmented ciliary
      epithelium may mimic an amelanotic malignant melanoma of the iris and should be
      considered in its differential diagnosis.

PMID- 9930173
TI  - Adenoma of nonpigmented ciliary epithelium with smooth muscle differentiation.
AB  - A 35-year-old man underwent successful iridocyclectomy for a ciliary body mass
      that was subluxating the lens and causing a secondary cataract.
      Histopathologically the mass proved to be a spindle cell tumor, but leiomyoma and
      melanoma were initially considered to be diagnostic possibilities. However,
      further studies and immunohistochemical studies revealed that the tumor probably
      arose from the nonpigmented ciliary epithelium. The spindle cells represented
      smooth muscle differentiation within the mass. The final diagnosis was adenoma of
      the nonpigmented ciliary epithelium with smooth muscle differentiation.

PMID- 9930174
TI  - Pigmented adenoma mimicking a juxtapapillary melanoma. A 20-year follow-up.
AB  - A 52-year-old white woman was first diagnosed with a tumor of the right optic
      nerve in 1972. She remained asymptomatic until 1992, when she had a seizure on
      the left side of her body from a frontoparietal glioblastoma multiforme.
      Ophthalmic examination revealed enlargement of the eye tumor. This case provides
      clinical documentation spanning 20 years of a growing, pigmented tumor of the
      optic nerve head shown histopathologically to be a retinal pigment epithelial
      adenoma.

PMID- 9930175
TI  - Can an eye in phthisis be rehabilitated? A case of improved vision with 1-year
      follow-up.

PMID- 9930176
TI  - Good visual outcome following laser therapy for proliferative radiation
      retinopathy.

PMID- 9930177
TI  - A confocal microscopic study of advancing wavelike epitheliopathy.

PMID- 9930178
TI  - Traumatic enucleation from a high-pressure water jet.

PMID- 9930179
TI  - A hereditary chiasmal optic neuropathy.

PMID- 9930180
TI  - Oculoglandular tularemia.

PMID- 9930181
TI  - Central retinal vein occlusion in a patient with IgG lambda monoclonal
      gammopathy.

PMID- 9930183
TI  - Spontaneous globe luxation associated with floppy eyelid syndrome and shallow
      orbits.

PMID- 9930182
TI  - Circumscribed choroidal hemangioma managed by transpupillary thermotherapy.

PMID- 9930184
TI  - Laser-induced chorioretinal anastomosis and central retinal vein occlusion.

PMID- 9930185
TI  - Basal vs reflex lacrimation.

PMID- 9930186
TI  - Examination of New Zealand's endemic Wiseana nucleopolyhedrovirus by analysis of
      the viral polyhedrin gene.
AB  - Insects of the genus Wiseana (Lepidoptera: Hepialidae) are major agricultural
      pests in New Zealand. Singly enveloped nucleopolyhedroviruses (SNPVs) isolated
      from three of the seven described Wiseana species have potential as biological
      control agents. As part of an effort to characterise the Wiseana SNPV genome the
      polyhedrin gene was cloned and the nucleotide sequence determined. The gene
      sequence was used, in conjunction with morphological and restriction endonuclease
      analysis, to compare isolates from different sites and species of Wiseana.
      Heterogeneity was detected within a single site, as well as between SNPV from
      separate Wiseana species. The extent of divergence between the nucleotide
      sequences was small enough, however, to consider three SNPVs from W. signata, W.
      cervinata and W. umbraculata as different strains of a single SNPV species. This
      improves the likely practicability of developing a single viral agent to control
      this pest complex. In addition, the virus polyhedrin gene sequence was used to
      estimate the phylogenetic relatedness of a W. signata SNPV to 16 other NPV from
      diverse insect genera. These comparisons suggest the Wiseana SNPV was unique
      within the Baculoviridae, but was more closely related to the group II NPVs.

PMID- 9930187
TI  - The reactivity of monoclonal antibodies against orf virus with other
      parapoxviruses and the identification of a 39 kDa immunodominant protein.
AB  - A panel of 27 mouse monoclonal antibodies (Mabs) was raised against orf virus.
      Sixteen of these Mabs reacted with a protein with a molecular mass of 65 kDa, 8
      reacted with a protein with a molecular mass of 39 kDa and three remain
      uncharacterised. Reactivity of the Mabs with a library of recombinant vaccinia
      viruses expressing various regions of the NZ-2 orf virus genome identified the
      approximate positions of the genes encoding these 2 immunodominant orf virus
      proteins. The gene encoding the 39 kDa protein was identified and sequenced. The
      protein was detected in an envelope fraction of orf virus and was shown to be
      homologous to the envelope protein encoded by the H3L gene of vaccinia virus. The
      65 kDa protein has not been fully chracterised, but the gene encoding it has been
      localised to a 10 kbp region of the orf virus genome. The Mabs were used to
      discriminate 4 parapoxviruses derived from sheep, 2 from cattle and 1 each from a
      seal and squirrel. Eighteen Mabs reacted with all 4 sheep viruses, 19 Mabs
      reacted with both cattle viruses, 6 recognised seal parapoxvirus and 2 recognised
      the squirrel parapoxvirus. Only one of the 27 Mabs reacted with all 8
      parapoxviruses suggesting it recognises a conserved epitope within the genus.

PMID- 9930188
TI  - Circular dichroism studies of CMV-D and CMV-S: two strains of cucumber mosaic
      cucumovirus with a different biological behaviour.
AB  - Cucumber mosaic cucumovirus is a plant virus in which a typical satellite RNA
      system is present, displaying a dualistic biological behaviour. In fact, it has
      been shown that satRNA is able either to aggravate or attenuate the viral disease
      symptomatology with a modulating capability going from death of the host plant to
      a surprising absence of symptoms. D-satRNA and S-satRNA have been considered the
      prototype necrogenic and non necrogenic satRNAs respectively. On the basis of
      circular dichroism spectroscopy, it is suggested that the different biological
      behaviours can be explained by taking into account the different capabilities
      exerted by S- and D-satRNAs in inducing structuring effects onto CMV-S and CMV-D
      genomic RNAs.

PMID- 9930189
TI  - Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma
      patients: comparative analysis of 40 full-length isolates.
AB  - We determined full-length nucleotide sequence of hepatitis B virus (HBV) genome
      in sera from 40 Japanese patients with HBsAg-positive hepatocellular carcinoma
      (HCC), in order to obtain information on HCC-specific characteristics, if any, of
      the HBV genome. Direct sequencing of the long distance PCR products starting from
      50 microliters of serum samples revealed that 95% of our isolates were of
      genotype C, and that mutations and deletions/insertions were very common. With
      respect to envelope protein genes, deletions and missense mutations were frequent
      in preS2, and the determinant a domain of HBsAg was rich in "antibody-escape"
      mutations. Within the precore/core region, the most remarkable mutation was the
      replacement of proline of wild type by other amino acids at codon 130 of the core
      gene, which was found in 58% of our isolates, while precore-stop mutation was
      found in 45%. Most interestingly, however, about 90% of our isolates had
      mutations at nt positions 1762 (A-to-T) and 1764 (G-to-A) within the core
      promoter, which had been implicated in "e-suppressive" phenotype of HBV genome. G
      to-A at nt 1613 and C-to-T at nt 1653 within enhancer II and T-to-C/A at nt 1753
      within core promoter were also evident: 38%, 53%, and 40%, respectively. It was
      interesting that some of the characteristics observed in our isolates form HCC
      patients had been previously implicated in fulminant hepatitis and/or acute
      exacerbation of chronic hepatitis.

PMID- 9930190
TI  - Some characteristics of a cellular receptor for virulent infectious bursal
      disease virus by using flow cytometry.
AB  - A flow cytometric virus binding assay that directly visualizes the binding of
      infectious bursal disease virus (IBDV) to its target cells was established. The
      chicken B lymphoblastoid cell line, LSCC-BK3, which is permissive for IBDV
      infection, bound high levels of the virus. Another B lymphoblastoid cell line,
      LSCC-1104-B1, bound low levels of the virus, although it was nonpermissive. No
      virus binding was detected in nonpermissive T lymphoblastoid cell lines. In the
      binding assay to heterogeneous cell populations of chicken lymphocytes, IBDV (a
      highly virulent OKYM strain) bound to 94% cells in the lymphocytes prepared from
      the bursa of Fabricius, 37% cells in those prepared from the spleen, 3% cells in
      those prepared from the thymus, and 21% cells in those prepared from the blood.
      Most of the cells, which bound the virus, were surface immunoglobulin M (SIgM)
      positive, but a small number of them were SIgM-negative. Additionally, the
      binding of IBDV to the LSCC-BK3 cells was affected by treatment of the cells with
      proteases and N-glycosylation inhibitors. These findings may indicate that the
      IBDV host range is mainly controlled by the presence of a virus receptor composed
      of N-glycosylated protein associated with the subtle differentiation stage of B
      lymphocytes represented mostly by SIgM-bearing cells.

PMID- 9930191
TI  - Determinants of pantropism of the F1-R mutant of Sendai virus: specific mutations
      involved are in the F and M genes.
AB  - Mutations in the fusion, F, protein of Sendai virus resulting in increased
      cleavability by ubiquitous host protease(s), and mutations in the matrix, M,
      protein resulting in bipolar budding, are both important determinants for the
      systemic infection in mice caused by the protease activating pantropic mutant, F1
      R. Several mutants of Sendai virus (BY, BF, and KD-M) with phenotypes of bipolar
      budding and/or increased cleavability of F protein were isolated. Genomic RNA
      sequence analysis of the F and M genes of the mutants revealed that several
      deduced amino acids in the F and M proteins were different from those of F1-R, T
      5 (a revertant of F1-R), and wild-type viruses. The BF and KD-M mutants that
      budded bipolarly and were also activated by ubiquitous proteases were examined
      for replication in tissue culture cells and in mice. All of the mutants exhibited
      multiple-step replication in MDCK, MDBK, and LLC-MK2 cells without trypsin, but
      formed plaques only in MDCK cells. One of the mutants, designated KD-52M, was
      similar to F1-R in that it formed plaques in all three cell lines without
      addition of exogenous protease. However, none of the mutants viruses, including
      KD-52M, caused a systemic infection in mice. The mutated M protein of F1-R
      enhances the disruption of microtubles. However, none of the mutants with a
      bipolar budding phenotype (BY, BF, and KD-M), disrupted the microtubules to the
      same extent as F1-R. All of these mutants had mutations in the M protein that
      were different from those found in F1-R. Taken together, these results suggest
      that mutations at Ser115 to Pro in the F protein and at Asp 128 to Gly and Ile210
      to Thr in the M protein of F1-R are the mutations specifically required for the
      systemic infection caused by F1-R.

PMID- 9930192
TI  - Localizations of NS3 and E proteins in mouse brain infected with mutant strain of
      Japanese encephalitis virus.
AB  - Infection with a mutant Japanese encephalitis virus (JEV) strain RP-2ms showed
      reduced neurovirulence than wild type or RP-9 strains after inoculation in BALB/c
      mice. However, higher intracellular viral titer was detected in Rp-2ms infected
      cultured cells. Localizations of non-structural 3 (NS3) and envelope (E) proteins
      were demonstrated by immunocytochemistry. NS3 protein was primarily found in the
      pyramidal neurons in cerebrum, in the molecular and granular layers of
      cerebellum. Neither E nor NS3 protein was detected in Purkinje cells of the
      cerebellum. Immunoelectron microscopic observations showed that E and NS3
      proteins were positive in JEV-induced membranous systems, mainly hypertrophic
      rough endoplasmic reticulum (rER) and membrane vesicle structure (MVS) but not
      smooth membrane structure. Virus particles were seen in the Golgi apparatus, rER,
      nuclear envelope, MVS and cytoplasmic vacuoles. Different mechanisms of
      intracellular trapping in vivo provide a possible basis for attenuation of RP-2ms
      strains of JEV.

PMID- 9930193
TI  - Spontaneous release of stable viral double-stranded RNA into the extracellular
      medium by influenza virus-infected MDCK epithelial cells: implications for the
      viral acute phase response.
AB  - The viral factor responsible for triggering the acute phase response, or 'flu'
      syndrome, associated with many acute viral infections is not defined. One
      candidate viral factor is double-stranded RNA (dsRNA) generated during viral
      replication. In this report we demonstrate by reverse-transcriptase polymerase
      chain reaction that nuclease-stable viral RNA was released from influenza
      infected MDCK epithelial cells at the time of cell lysis. Removal of virion
      associated RNA by ultracentrifugation left equal amounts of positive- and
      negative-strand viral RNA in the medium that resisted degradation by endogenous
      RNase in the medium and by exogenous RNase added prior to phenol extraction.
      These data are the first demonstration that viral RNA with characteristics of
      dsRNA is spontaneously released from dying influenza virus-infected cells, and
      thus is available to amplify cytokine induction and contribute to systemic
      disease.

PMID- 9930194
TI  - Characterization of the large (L) RNA of peanut bud necrosis tospovirus.
AB  - The nucleocapsids purified from peanut plants systemically infected with peanut
      bud necrosis virus (PBNV), a member of the genus Tospovirus, contained both
      viral(v) and viral complementary(vc) sense L RNAs. Defective forms of L RNA
      containing 'core polymerase region' were observed. The full length L RNA of PBNV
      was sequenced using overlapping cDNA clones. The 8911 nucleotide L RNA contains a
      single open reading frame (ORF) in the vc strand, and encodes a protein of 330
      kDa. At the 5' and 3' termini of the v sense RNA there were 247 and 32 nt
      untranslated regions, respectively, containing an 18 nt complementary sequence
      with one mismatch. Comparisons of the predicted amino acid sequence of the L
      protein of PBNV with other members of Bunyaviridae suggest that the L protein of
      PBNV is a viral polymerase. The L protein had highest identity in the 'core
      polymerase domain' with the corresponding regions of other tospoviruses, tomato
      spotted wilt virus and impatiens necrotic spot virus.

PMID- 9930195
TI  - Characterization of a bovine herpesvirus 4(BHV-4) 1.1-kb RNA and its
      transactivation by BHV-4 immediate-early 2 gene product.
AB  - We determined the structure of a 1.1-kb cytoplasmic polyadenylated RNA
      transcribed from a region of the bovine herpesvirus 4 (BHV-4) genome not
      conserved among gammaherpesviruses by sequencing its cDNA, by S1 nuclease
      analysis, and by primer extension analysis. We found that the RNA consists of a
      short, approximately 193-nucleotide (nt), 5' exon spliced to a 799-nt 3' exon and
      contains two short (53 and 57 codons) overlapping open reading frames (ORFs). The
      53-codon ORF was previously designated BORFE1. Neither ORF exhibits detectable
      amino acid sequence homology with ORFs of other gammaherpesviruses. The 1.1-kb
      RNA promoter-regulatory region was specifically transactivated by the BHV-4 IE2
      gene product, a homolog of the Epstein-Barr virus R transactivator, in
      cotransfection assays. In gel retardation experiments, IE2 protein formed a
      complex with DNA in a 129-bp fragment between -23 and -151 relative to the
      transcription start site of the 1.1-kb RNA, and less efficiently with a 57-bp
      subfragment between -78 and -22. A sequence similar to sequences of IE2-binding
      fragments of other BHV-4 IE2 responsive promoters was found partly in the 57-bp
      subfragment, extending into the portion of the 129-bp fragment not found in the
      57-bp fragment. The 129-bp fragment, but not the 57-bp fragment, was sufficient
      for transactivation of a promoterless chloramphenicol acetyl transferase (CAT)
      reporter gene by IE2. However, the 129-bp fragment did not function efficiently
      as an IE2-responsive enhancer when inserted approximately 140 base pairs (bp) 5'
      to the transcription start site of a CAT reporter gene driven by an enhancerless
      simian virus 40 early promoter. Based on this and other observations, we propose
      that IE2 functions as a promoter factor rather than an enhancer factor.

PMID- 9930196
TI  - Prokaryotic expression of human cytomegalovirus pUS22 and its reactivity with
      human antibody.
AB  - This work demonstrates that antibodies to the product of the recombinant pUS22 of
      human cytomegalovirus (HCMV) are present in human sera during natural infection.
      US22 gene product has been identified as a member of the US22 family which may be
      secreted from infected cells. It is an early protein of 593 amino acids, 76 Kd in
      molecular weight. US22 seems to be an antigen which stimulates a good IgG
      response. In fact specific IgGs were found in approximately 40% of the CMV
      positive sera irrespective of their anti-CMV IgG titer. Specific IgM antibodies
      to pUS22 were observed exclusively during primary infection and in the sera with
      a high anti-CMV IgM titer. pUS22 could be considered for inclusion in a cocktail
      of CMV recombinant proteins to determine seropositivity to CMV and also to
      diagnose an active CMV infection.

PMID- 9930197
TI  - Genomic mapping of a calicivirus VPg.
AB  - We identified a primate calicivirus (Pan-1) VPg in Pan-1-infected cells. The Pan
      1 VPg was associated with both genomic and subgenomic RNAs. RNase digestion of
      Pan-1 RNA yielded a residual protein of 16 kDa. The N-terminal sequence of Pan-1
      VPg was determined by direct amino acid sequencing and mapped to a region of the
      genome equivalent to picornavirus VPgs. Alignment of this protein sequence with
      similar regions of other calicivirus genomes allowed identification of conserved
      amino acid motifs and potential boundaries of the calicivirus VPg genes.
      Proteinase K treatment abolished the infectivity of Pan-1 RNA, suggesting that
      Pan-1 VPg is required for RNA infectivity.

PMID- 9930198
TI  - Complete nucleotide sequence of the genome organization of RNA2 of patchouli mild
      mosaic virus, a new favavirus.
AB  - The complete nucleotide sequence and the genome organization of the RNA 2 of a
      patchouli mild mosaic virus (PaMMV) was determined. The sequence consists of 3591
      nucleotides and contains a single long open reading frame sufficient to code for
      118 K protein. Three proteins of 52 K, 44 K and 22 K could be encoded by the
      PaMMV RNA 2 genome. Our analysis of the N-terminal sequences of two species of
      coat protein (CP) allowed precise location of the CP cistrons within the
      polyprotein. 44 K and 22 K proteins are the coat proteins. The positions of the
      cleavage sites are Gln/Ala between 44 K and 22 K coat proteins and Gln/Gly
      between 52 K and 44 K proteins. Comparison of PaMMV RNA 2 with comoviral and
      nepoviral RNA 2 showed no sequence similarity. These results as well as previous
      serological studies strongly suggest that PaMMV is a member in the genus
      Fabavirus.

PMID- 9930199
TI  - Induction of apoptosis in HEp-2 cells by infection with herpes simplex virus type
      2.
AB  - Although herpes simplex virus type 1 (HSV-1) does not induce apoptosis in
      infected HEp-2 cells, herpes simplex virus type 2 (HSV-2) did induce apoptosis in
      a small but significant fraction of the same cells. Apoptosis was not observed in
      Vero or HeLa cells infected with HSV-2. In addition, HSV-2 infection in the
      presence of cycloheximide induced extensive apoptosis of HEp-2 or HeLa cells.

PMID- 9930200
TI  - Construction of full-length cDNA clones of lettuce mosaic virus (LMV) and the
      effects of intron-insertion on their viability in Escherichia coli and on their
      infectivity to plants.
AB  - A full length cDNA copy of the genomic RNA of lettuce mosaic virus (LMV) was
      constructed under the control of an enhanced CaMV 35S promoter and of the NOS
      terminator. This construct was found infectious when inoculated to lettuce
      plants. The intron II of the bean nitrite reductase gene was engineered into the
      LMV FL cDNA in order to relieve possible deleterious effects of viral sequences
      to Escherichia coli cells and to evaluate the effects of the presence of the
      intron on the FL cDNA infectivity. The intron-less FL cDNA was found to be as
      stable as its intron-containing counterpart in E. coli. Sequence analysis of
      progeny RNA derived from plants inoculated with the intron-containing FL cDNA
      demonstrated that the inserted intron was perfectly spliced out. The symptoms
      induced in lettuce by either the intron-less or the intro-containing constructs
      were identical to those caused by the wild-type virus. However a slight delay in
      the establishment of infection in lettuce and a more obvious lag in Nicotiana
      benthamiana were observed with the intron-containing FL cDNA.

PMID- 9930201
TI  - Structure analysis of the rice yellow stunt rhabdovirus glycoprotein gene and its
      mRNA.
AB  - The nucleotide sequence of the glycoprotein (G) gene of rice yellow stunt
      rhabdovirus (RYSV) was determined. The G gene is 2158 nucleotides long and
      contains an open reading frame of 2007 nucleotides encoding a protein with a
      calculated molecular mass of 75,358 Da. Furthermore, the 5'- and 3'-terminal
      sequences of the G protein mRNA were defined by the RACE method. Non-viral
      nucleotides appear to be present at the 5' end of G mRNA. The G protein contains
      an N-terminal signal peptide of 32 amino acids, C-terminal transmembrane and
      cytoplasmic domains, ten potential glycosylation sites and four stretches of a-d
      hydrophobic heptad-repeats.

PMID- 9930202
TI  - The nucleotide sequence of the 3'-terminal region of dasheen mosaic virus
      (Caladium isolate) and expression of its coat protein in Escherichia coli for
      antiserum production.
AB  - A caladium isolate of dasheen mosaic virus (DsMV-Ch) was cloned as cDNA from
      genomic RNA. The sequence of the 3'-terminal 3158 nucleotides, which consisted of
      the 3'-terminus of the NIa gene, the NIb gene, the coat protein (CP) gene, and a
      246-nucleotide non-coding region, was between 57-68% similar at the nucleotide
      level and 72-82% similar at the amino acid level when compared with other
      potyviruses. Phylogenetic analysis of aligned, selected potyviral CP sequences
      indicate that DsMV-Ch is similar to DsMV isolates infecting taro and closely
      related to the bean common mosaic virus subgroup in the genus Potyvirus. A
      recombinant DsMV-Ch CP (approximately 39 kDa) expressed in E. coli was used as an
      immunogen and the resulting antiserum reacted with DsMV and several other
      potyviruses in Western blots and indirect ELISA.

PMID- 9930203
TI  - Transmissible gastroenteritis virus induced apoptosis in swine testes cell
      cultures.
AB  - Transmissible gastroenteritis virus (TGEV) is a coronavirus which causes severe
      gastroenteritis and atrophy of intestinal villous epithelial cells in piglets.
      However, the mechanism of cell death caused by TGEV is not known. In this study,
      we report that TGEV induces cell death by apoptosis. TGEV-induced apoptosis was
      demonstrated by agarose gel electrophoresis, electron microscopy, and terminal
      deoxytransferase digoxigenin-dUTP nick end labeling (TUNEL). Double labeling
      experiment confirmed the result from electron microscopy and showed that most of
      the apoptotic cells were bystander cells as they were negative for TGEV nucleic
      acids. Results of this study indicate that TGEV induces apoptosis in vitro and
      that most of the cells undergoing apoptosis are bystander cells, thus amplifying
      the cytopathic effect of TGEV.

PMID- 9930204
TI  - Infectivity of African cassava mosaic virus clones to cassava by biolistic
      inoculation.
AB  - Clones of an African cassava mosaic virus isolate originating from Nigeria (ACMV
      NOg) were shown to be infectious to cassava by biolistic inoculation. The
      production of pseudorecombinants between ACMV-NOg and clones of an ACMV isolate
      originating from Kenya (ACMV-K) indicated that the lack of infectivity of ACMV-K
      to cassava was due to defect(s) in the DNA B genomic component; this component
      encodes two proteins involved in cell-to-cell movement. This is the first
      demonstration of infectivity of a cloned geminivirus to cassava and conclusively
      proves that ACMV is the causative agent of cassava mosaic disease. The potential
      uses of infectious ACMV clones and the means by which to introduce them into
      cassava are discussed.

PMID- 9930205
TI  - Classification, nomenclature, and database development for hepatitis C virus
      (HCV) and related viruses: proposals for standardization. International Committee
      on Virus Taxonomy.

PMID- 9930206
TI  - Drugs for asthma.

PMID- 9930207
TI  - [Communications culture in digital networks].

PMID- 9930208
TI  - [Spondarthritis hyperostotica pustulo-psoriatica: nosologic study with clinical
      and radiologic presentation in relation to the SAPHO syndrome].
AB  - Spondarthritis hyperostotica pustulo-psoriatica (Spond.hyp.pp-Schilling),
      corresponding nosologically to pustulotic arthroosteitis, is a dermato-skeletal
      "double system" disease of adults. It consists of the triad (a) palmo-plantar
      pustulosis (Ppp) or, alternatively, Konigsbeck-Barber-type psoriasis, (b)
      sternocostoclavicular hyperostosis (SCCH), and (c) truncal-skeletal changes with
      syndesmophite-like, hyperostotic and/or parasyndesmophite-like ossifications of
      layers of the anterior vertebral ligament taken together in the sense of a
      desmophytal hyperostosis. There is also a potential for sclerosing inflammatory
      arthritis of the sacro-iliac joints and "dry" inflammatory arthritis of
      peripheral joints. Thus, the pustulo-psoriatic terrain seems to have a decisive
      influence on osseous pathology. A total of 38 cases from a study during the years
      1982 to 1992 is analysed with regard to morphological characteristics. Rare cases
      with diaphyseal and pelvic hyperostotic lesions subsequent to bland sclerosing
      osteomyelitis constitute an overlapping region to chronic recurrent multifocal
      osteomyelitis (CRMO) and illustrate the relationship between hyperostotic
      spondarthritis and CRMO. The syndromes of "acquired hyperostosis" and "SAPHO",
      the former more radiologically oriented and the latter more clinically oriented,
      together with mainly CRMO and hyperostotic spondarthritis and its forms,
      constitute the "Spond.hyp.pp.". Although hyperostosis is a guidepost for the
      radiologist and SAPHO symptoms are one for the clinician, the syndrome does not
      represent a diagnosis by itself and requires further differentiation. In this
      report the entity "Spond.hyp. pp." is considered and required contributions from
      rheumatologically and osteologically oriented radiologist.

PMID- 9930209
TI  - [Mortality and morbidity conference in radiology].
AB  - PURPOSE: To establish a morbidity and mortality conference in a radiology
      department as an instrument of quality assurance. METHODS: Since April 1995 a
      monthly conference is held in the radiology department. Complications of invasive
      diagnostic procedures (angiography and biopsy) and minimal invasive interventions
      are presented. Cases of morbidity (major complications) and mortality (deceased
      patients, who were examined or treated in the radiology department before) are
      discussed. The identification of cases was possible due to a data base that
      included all such procedures prospectively. RESULTS: Twenty cases of major
      complications were identified and discussed during 18 morbidity and mortality
      conferences in 1996 and 1997. Out of the 9 patients who died in our hospital and
      previously had an interventional procedure in the radiology department, one case
      was identified as being procedure-related. An analysis of this case was
      performed. CONCLUSION: With a formalised structure of case detection, the
      morbidity and mortality conference becomes a tool of a complete analysis of
      complications and a meaningful instrument for the solution of problems concerning
      procedure-related complications.

PMID- 9930210
TI  - [Colliculus atlantis--a rarely observed anatomic structure--in a transoral
      roentgen image of the thoracic spine].
AB  - PURPOSE: To study the time and mode of the development of the colliculus
      atlantis, the rate of its occurrence, the causes for its absence, and the
      radiological-clinical importance in the analysis of open-mouth-view radiographs.
      MATERIAL AND METHODS: Retrospective analysis of standardized radiographs of the
      cervical spine in more than 20,000 adults and 100 children. Study of 234 human
      skeletons of different ages and of 38 isolated adult atlases. Cadaveric
      dissection of 42 adults (age 48-87). Axial radiographs of isolated atlases and
      analysis of the bony structures of the colliculus atlantis. RESULTS: The
      colliculus atlantis develops between age 10 and 13 years. It is always present
      after age 13 years. For the development of the colliculus atlantis a normal
      function of the craniocervical joints is necessary. In congenital dysmorphias of
      the craniocervical region with dysfunction of the craniocervical joints and in
      fractures of the dens axis before age 10 years with instable healing the
      colliculus atlantis is absent. CONCLUSIONS: The colliculus atlantis is developed
      at age 13 years apart from some rare exceptions as mentioned. Changes of the site
      and the structure of the colliculus atlantis allow an early diagnosis of certain
      traumatically and inflammatory diseases of this region. Furthermore, it serves as
      an additional parameter in functional analysis of the craniocervical joints.

PMID- 9930211
TI  - [1H MR spectroscopy of the lumbar spine in diffuse osteopenia due to plasmacytoma
      or osteoporosis].
AB  - PURPOSE: To evaluate the role of in vivo 1H MR spectroscopic determination of
      relaxation times and of fat and water content to differentiate between
      infiltration of multiple myeloma or osteoporosis in patients with roentgenologic
      unclear demineralization of the lumbar spine. PATIENTS, MATERIALS AND METHODS:
      Ten patients each with osteoporotic reduction of bone mineral density (BMD),
      histologically proven multiple myeloma who showed only diffuse tumor
      manifestations without tumor compression fractures in the spine, and volunteers
      were investigated. Osteoporosis was confirmed by dual-energy X-ray absorptiometry
      (DXA) (Hologic QDR 2000 device, Siemens Medical Systems). The MR investigations
      were performed with a 1.5 T whole body system (Gyroscan S15/ACS II, Philips
      Medical Systems). Localized MR spectra from a cubic volume of about 8 cm3 were
      acquired by the PRESS technique. Chemical shift selective T1 relaxation times
      were obtained from an IR series, T2 was measured by variation of the interval
      between the first and the second echo in the volume selection scheme. Statistical
      analysis was done using the Kruskal-Wallis test and the Mann-Whitney test with
      the software SPSS. RESULTS: There were highly significant differences in T2
      values and fat content between patients with osteoporosis and multiple myeloma.
      T2 values were decreased in osteoporosis (37 ms and 59 ms vs. 44 ms and 70 ms in
      plasmocytoma) and fat content was decreased in multiple myeloma (20% vs 31% and
      34% in volunteers and osteoporosis). Between volunteers and patients with
      osteoporosis the differences in the T2 of the fat component was significantly
      different. CONCLUSIONS: In our preliminary experience MRS is helpful in the
      differential diagnosis of bony demineralization. It enables a differentiation
      between osteoporosis and diffuse multiple myeloma. T2 value measurements may be
      helpful in the diagnostic trial of osteoporosis.

PMID- 9930212
TI  - [Rivet-like titanium clamps for refixation of bone covers after craniotomy-
      radiologic identification, safety and image quality in CT and MR studies].
AB  - PURPOSE: The MRI and CT compatibility of a new design of metallic fixation
      implants for cranial bone flaps was investigated experimentally and following
      clinical application in craniotomy patients. Is imaging quality impaired through
      implant-induced artifacts? METHODS: Possible induced movement and heating of the
      clamp implant as well as the magnitude of susceptibility artifacts were assessed
      experimentally by MRI at 1.5 T. Additionally, implant-induced artifacts were
      evaluated under clinical conditions for all relevant MRI-sequences in 100
      craniotomy patients whose skull flaps were re-affixed using the new clamp
      implant. RESULTS: In T1-weighted spin echo and fast spin echo sequences the sizes
      of implant-induced artifacts were equal to the size of the implant or slightly
      larger; in T2-weighted gradient echo images artifacts were maximally double the
      size of the implant itself. Induced movement or heating was not observed.
      CONCLUSIONS: The safety in radiological imaging of titanium clamp implants for
      fixation of craniotomy bone flaps was established experimentally as well as under
      clinical conditions. The clamps can be easily identified by radiological imaging,
      cause no hazards to the patients, and have little effect on image quality.

PMID- 9930213
TI  - [Use of high resolution color Doppler sonography in diagnosis of temporal
      arteritis].
AB  - PURPOSE: To define sonographic signs of arteritis temporalis using color coded
      duplex sonography. METHODS: 20 patients with clinically suspected temporal
      arteritis were examined with color coded Doppler ultrasound prior to temporalis
      biopsy. The investigation included the temporal artery on both sides and
      documentation was performed with color prints of the longitudinal orientation of
      both temporal arteries. All patients had an unilateral biopsy of the temporal
      artery. RESULTS: 6/20 patients had histologically confirmed temporal arteritis.
      All patients showed a paravasal zone of lower echogenicity (halo-sign) along the
      temporal artery. 12/14 patients without temporal arteritis showed no halo-sign.
      However, a halo-sign was found in 2/14 patients without temporal arteritis which
      could not be distinguished from the halo-sign observed in patients with temporal
      arteritis. CONCLUSIONS: A halo-sign could be detected in the majority of patients
      with arteritis temporalis in concordance with the recent published findings of
      Schmidt et al. However, a definite specificity of this halo-sign must be
      rejected.

PMID- 9930214
TI  - [MRI diagnosis of right ventricular dysplasia].
AB  - PURPOSE: Right ventricular dysplasia (RVD) represents an important cause of
      sudden death and ventricular arrhythmias in young patients. The aim of this study
      was to describe diagnostic diagnostic criteria and the MR-tomographie aspects of
      the disease. METHODS: 34 patients with clinically suspected RVD were examined by
      0.5-T MRI (cardiac-gated T1-weighted spin echo sequences and cine gradient echo
      sequences). RVD was confirmed in 16 patients and ruled out in 18 patients. MR
      images were evaluated for presence of: 1. right myocardial fatty infiltration, 2.
      dilatation of the right ventricle, 3. dilatation of the right ventricular outflow
      tract, and 4. localised right ventricular aneurysm. RESULTS: Right myocardial
      fatty infiltration was detected by MRI in 11 of 16 patients (69%) with RVD.
      Dilatation of the right ventricle was seen in 5 patients, dilatation of the right
      outflow tract in one patient, and localised right ventricular aneurysm in two
      patients with RVD. CONCLUSIONS: MRI is able to demonstrate fatty replacement of
      right ventricular myocardium in most cases and plays an important role in the
      diagnosis of RVD.

PMID- 9930215
TI  - [Determination of contour clarity in contrast-enhanced MR angiography: definition
      and clinical evaluation exemplified by ECG-triggered imaging of the thoracic
      aorta].
AB  - PURPOSE: The sharpness of the vessel contour in 3D contrast-enhanced MR
      angiography is defined by particular measurements of the signal intensity. To
      evaluate the facilities of an ECG-triggered data acquisition to optimize the MRA
      image quality of the thoracic aorta. METHOD: In phantom studies the sharpness of
      the vessel contour was defined as the distance of the extraluminal signal-minimum
      to the extraluminal maximum. Afterwards 30 examinations of the thoracic aorta
      with and without the use of an ECG-triggering were evaluated with regard to the
      sharpness of the vessel outline. RESULTS: The presented definition of the signal
      intensity is suitable for objective measurements of the vessel outline. At the
      level of the ascending aorta, ECG-triggered data acquisition increased the image
      quality significantly. CONCLUSIONS: An easy, practicable definition enables
      measurements of the sharpness of the vessel outline. ECG-triggered data
      acquisition is recommended for optimal visualization, especially of the ascending
      aorta.

PMID- 9930216
TI  - [Diagnosis of primary sclerosing cholangitis: prospective comparison of MR
      cholangiography with endoscopic retrograde cholangiography].
AB  - PURPOSE: To assess the accuracy of MR cholangiography (MRC) in the diagnosis of
      primary sclerosing cholangitis (PSC) in comparison to endoscopic retrograde
      cholangiography (ERC). METHOD: 20 patients with PSC were examined by ERC and MRC
      (1.0 T, HASTE sequence). Visualization and pathologic changes of the extra- and
      intrahepatic bile ducts were evaluated with both methods. RESULTS: Mural
      irregularities of the common bile duct were seen with MRC in 6/7 cases, stenoses
      and dilatation of the common bile duct were detected correctly in all patients.
      Diffuse, multifocal strictures of the intrahepatic bile ducts were the most
      common intrahepatic findings and correctly diagnosed in almost all patients.
      Mural irregularities of the intrahepatic ducts in early stages may be missed by
      MRC because of the limited spatial resolution. MRC is superior to ERC in
      visualization of nonopacified intrahepatic ducts. CONCLUSIONS: MRC is a reliable,
      non-invasive method to detect typical diagnostic features of PSC. It should be
      considered as an adjunct to ERC in patients with suspected PSC for primary
      diagnosis and as an alternate method for follow-up studies.

PMID- 9930217
TI  - [Criteria for ultrasound differentiation of small angiomyolipomas (< or = 3 cm)
      and renal cell carcinomas].
AB  - PURPOSE: The purpose of this prospective study was to analyze whether ultrasound
      (US) features are helpful for the differentiation and characterization of small
      solid (< or = 3 cm) renal masses. MATERIALS AND METHODS: 70 small solid (< or = 3
      cm) renal masses were evaluated sonographically with respect to size, location,
      echogenicity, homogeneity, shadowing, hypoechoic rim, and cystic regions. In
      addition, all masses were evaluated with spiral-computed tomography (CT). A
      diagnosis of angiomyolipoma (AML) was made when a lesion contained components
      with attenuation of fat (> -10 HU). The amount of fat and soft tissue of an AML
      detected on CT was correlated with the presence of shadowing seen on sonography.
      RESULTS: 10 (29%) of the 35 renal cell carcinomas (RCC) were hyperechoic to renal
      parenchyma, but no RCC was as echogenic as the renal sinus fat. Acoustic
      shadowing was only observed in AML. 11 (34%) AML with shadowing tended to have a
      larger amount of soft tissue. A hypoechoic rim and cystic regions were only found
      in RCC. 14 of 35 (40%) RCC showed a hypoechoic rim. Cystic regions were found in
      12 of the 35 RCC (34%). CONCLUSIONS: Renal cell carcinomas display a broad range
      of echogenicities indicating that small RCC (< or = 3 cm) and AML are not
      definitely distinguishable by their type of echogenicity. The presence of
      shadowing, a hypoechoic rim, and cystic regions enable differentiation of small
      (< or = 3 cm) AML from RCC with a high specificity. Accordingly, sonography has
      the potential to characterize small (< or = 3 cm) hyperechoic renal masses, with
      high specificity. However, the low sensitivity of these US features may require a
      CT for accurate diagnosis.

PMID- 9930218
TI  - [Endoluminal therapy of infrarenal aortic aneurysms with the Talent system-
      initial experiences with a new endoprosthesis].
AB  - PURPOSE: To report the early clinical experience with the Talent stent-graft
      system in the treatment of infrarenal aortic aneurysms. MATERIALS AND METHODS:
      The study group comprised 15 males aged from 51-79 years. A bifurcated Talent
      stent-graft was implanted in 9 patients with type B or C aneurysms, a tube graft
      in 6 patients with a type A aneurysm. The stent-grafts were introduced via a
      surgical femoral cut-down, for a bifurcated graft a bilateral surgical access was
      needed. All procedures were performed as teamwork by radiologists and vascular
      surgeons under general anaesthesia in the angiography suite. RESULTS: Primary and
      secondary technical successes were 80 and 86%, respectively. Technical failures
      were due to access site problems (n = 1; elective open repair), malpositioning of
      the prosthesis (n = 1; immediate conversion to open surgery), and primary distal
      leakage (n = 1; elective occlusion by means of distal stent-graft extension). One
      patient died 15 days after an uneventful stent-graft insertion (30-day mortality
      6%). No complications were observed during a mean follow-up period of 7.8 months.
      The aneurysmal diameter decreased in 6 patients and remained unchanged in the
      others. CONCLUSIONS: The Talent system revealed satisfactory early results which
      are comparable to competitive stent-graft systems. An advantage of this stent
      graft device is the availability in a wide range of dimensions. A major
      disadvantage is the large introducer system (french size 22-27).

PMID- 9930219
TI  - [Temperature stress for patients in routine magnetic resonance examinations].
AB  - PURPOSE: To determine energy exposure and temperature changes in routine magnetic
      resonance imaging practice. MATERIALS AND METHODS: Body core and skin
      temperatures were compared in 155 persons (143 patients, 12 volunteers)
      undergoing routine magnetic resonance examinations with a 1.5 T field-strength
      magnetic resonance tomography unit using a fluoroptic temperature measurement
      system. RESULTS: Average applied energy was 0.3 W/kg for whole body and 1.92 W/kg
      for spatially localized SAR. The maximum whole-body SAR was 1.43 W/kg spatially
      localized. Body core temperatures differed from those of the control group by a
      median 0.1 degree C and only a few patients (16.8%) exceeded the limit (+/- 0.5%)
      at which regulatory mechanisms set in. All patients remained within the normal
      physiological circadian temperature range (+/- 1 degree C). Skin temperature rose
      a median 0.49 degree C, with a maximal increase of 5.31 degrees C, which may be
      considered to be within the limits of physiological temperature change.
      CONCLUSIONS: Clinically relevant warming of the body is unlikely in routine
      magnetic resonance imaging practice.

PMID- 9930220
TI  - [Experimental model of early chronic pelvic vein thrombosis with occlusion
      spirals and thrombin].
AB  - PURPOSE: To create an early chronic venous thrombosis with good comparability to
      human venous thrombosis for evaluation of new thrombectomy systems. METHODS:
      Using a transjugular approach, three dacron-fibered occlusion coils were placed
      into the proximal common iliac vein of 7 pigs under general anesthesia. The
      coiled common iliac vein was blocked by the use of a balloon occlusion catheter,
      and 500 units of thrombin were injected into the "coil basket". One hour later,
      the balloon catheter was deflated and removed. After three days, the thrombus was
      controlled by phlebography and histology. RESULTS: The induction of thrombi was
      successful in all cases. The mean length of the thrombi was 60 mm and the mean
      diameter was 10 mm. Histologically, the thrombus consisted of a laminated plug of
      fibrin and platelets as well as clots in the sense of a mixed thrombus with signs
      of a beginning organization. Considering the cellular composition and the
      histological aspect, the thrombi met the criteria for early chronic venous
      thrombosis in humans. CONCLUSION: The presented experimental thrombus model is
      easy to perform and enables a good comparability to early chronic human venous
      thrombosis.

PMID- 9930221
TI  - [MRI-assisted bile duct drainage: evaluation of passive catheter imaging in an
      animal model].
AB  - PURPOSE: To investigate interactive MR-assisted bile duct drainage in pigs with
      the passive visualization technique using near real-time imaging. METHODS: 8 bile
      duct drainages were placed in an open low-field MR system (0.2 Tesla) in 4 pigs
      with surgically induced cholestasis. After planning the intervention with
      magnetic resonance cholangiography (MRC), both the puncture and catheter
      placement were interactively guided using a fast T2-weighted true FISP sequence.
      RESULTS: MRC enabled interventional planning in all puncture attempts. Punctures
      were unproblematic in all attempts, the bile ducts were punctured 6 times after
      the first and twice after the second attempt. Placement of the passively visible
      catheter was successful in all animals. The applied sequence enables interactive
      fluoroscopy-like positioning of the devices. CONCLUSION: The procedure introduced
      here enables reliable and fast placement of a bile duct drainage in an animal
      model using a low-field MR system.

PMID- 9930222
TI  - [Stent placement with real time MRI guidance: initial animal experiment
      experiences].
AB  - PURPOSE: The aim of this study was to test the feasibility of iliac artery stent
      placement under MR guidance with real-time MR radial scanning in an animal model.
      MATERIALS AND METHODS: The experiments were performed on three pigs in a 1.5 T
      scanner. Radial scanning with a gradient echo technique (TR 8.4 ms, TE 3.6 ms,
      flip angle 10 degrees) was used. A dedicated backprojector performed the
      reconstruction of the raw data in real-time. The resulting MR-images were
      displayed on LCD screens beside the magnet. The sliding window reconstruction
      technique allowed image acquisition at a frame rate of 16 images per second. MR
      compatible self-expanding stents with a diameter of 8 mm and a length of 3 cm
      were placed into the left iliac artery. Their positions were verified by digital
      subtraction angiography (DSA) and compared to MRI. RESULTS: All stents were
      successfully placed. Stent positions as monitored by real-time MR were identical
      to those seen on DSA images. The time needed for exact positioning of the scan
      plane ranged from 15 to 30 minutes. Stent placement itself took 8 minutes on
      average. CONCLUSION: Radial scanning applied together with the sliding window
      reconstruction technique allows placement of stents in iliac arteries under real
      time MR control.

PMID- 9930223
TI  - [Value of spirometry-gated high resolution computerized tomography of the lung
      during inspiration and expiration].
AB  - PURPOSE: To compare mean lung density (MLD) of paired inspiratory and expiratory
      thin-section CT scans acquired after patient instruction or using spirometric
      gating. MATERIALS AND METHODS: 21 patients (13 m, 8 f. median age 59 years, two
      with normal lung function, 15 with obstructive, 4 with restrictive impairment)
      underwent thin-section CT. Paired inspiratory and expiratory scans were performed
      in the upper, middle and lower lung fields. They were acquired after automatic
      patient instruction with constant intervals between instruction and scan.
      Spirometrically gated scans were acquired within 4 days at 80% and 20% of vital
      capacity (VC) which has been determined on the CT scanner in supine position
      directly prior to the examination using the built-in spirometric option.
      Semiautomatic segmentation of the lung was performed and MLD was calculated. VC
      of pulmonary function testing was available for correlation. RESULTS: Inspiratory
      MLD was -828 +/- 71 HU with spirometric gating and -818 +/- 87 HU without.
      Expiratory MLD was -750 +/- 119 HU (increase 78 +/- 58 HU) with spirometric
      gating and -748 +/- 119 HU (increase 70 +/- 46 HU) without. All differences were
      non-significant. Intraindividual differences were 10 +/- 21 HU for inspiration
      and 2 +/- 36 HU for expiration. VC under CT-conditions was significantly smaller
      than that known from pulmonary function tests (1.9 +/- 0.71 vs. 2.7 +/- 0.81, p <
      0.005). CONCLUSION: Spirometric gating does not lead to different results for MLD
      as compared with acquisition of paired inspiratory and expiratory thin-section CT
      after automatic patient instruction.

PMID- 9930225
TI  - [Bilateral agenesis of the internal carotid artery: diagnosis with magnetic
      resonance tomography].

PMID- 9930226
TI  - [Epigastric "Gaucher cell pseudotumor": image morphological and histological
      characteristics].

PMID- 9930224
TI  - [Spiral CT vesiculography--a new examination technique in patients with
      histologically verified prostate carcinoma].
AB  - PURPOSE: Development of an imaging method for detection of seminal vesicle
      invasion in patients with histologically proven carcinoma of the prostate.
      MATERIALS AND METHODS: In 24 patients with histologically proven carcinoma of the
      prostate we preoperatively performed an antegrade vaso-vesiculography with non
      ionic, iodine-containing contrast agent followed by a spiral CT of the seminal
      vesicles. RESULTS: In 21 patients we achieved both a bilateral and a bulging
      enhancement of the seminal vesicle lumen. The method is introduced and described
      in detail. CONCLUSIONS: Intraductal application of contrast agent just before
      spiral CT results in unfold and bulging enhanced seminal vesicles. From the
      differentiation of the lumen, the wall, and the surrounding fat of the seminal
      vesicles as well as the enhanced ejaculatory ducts we expect information on
      tumorous infiltration in cases of histologically proven carcinomas of the
      prostate.

PMID- 9930227
TI  - Plasmacytoma of the pancreas: CT and MRI appearance.

PMID- 9930228
TI  - [Endovascular therapy of a saccular aneurysm of the abdominal aorta].

PMID- 9930229
TI  - [Obsolete methods in examination of the liver with MRI].

PMID- 9930230
TI  - Rural health and human rights.

PMID- 9930231
TI  - Medical staffing in the former Transkei--an alternative licensing arrangement
      needed.

PMID- 9930232
TI  - Laparoscopic-assisted vaginal hysterectomy superfluous?

PMID- 9930233
TI  - Pernkopf's atlas.

PMID- 9930234
TI  - Community-acquired pneumonia.

PMID- 9930235
TI  - AIDS and informed consent.

PMID- 9930236
TI  - Sick certificates.

PMID- 9930237
TI  - Poisoning with boron trifluoride.

PMID- 9930239
TI  - Plan to counter medical fraud.

PMID- 9930238
TI  - TRC recommends fundamental health sector reform.

PMID- 9930240
TI  - Serial killers from the homeopathic view.

PMID- 9930241
TI  - US expert pours cold water on formularies.

PMID- 9930242
TI  - Plan for transfusing one's own blood.

PMID- 9930243
TI  - SAMA supports tobacco control.

PMID- 9930244
TI  - A life at the cutting edge: Walter Prozesky. Interview by Jonathan Spencer Jones.

PMID- 9930245
TI  - Medical savings accounts.

PMID- 9930246
TI  - Peer review.

PMID- 9930247
TI  - With cap in hand.

PMID- 9930248
TI  - Chronic primary headache--reducing the risk of treatment.

PMID- 9930249
TI  - Are our sportsmen and women getting a fair medical deal?

PMID- 9930250
TI  - Implementation of primary health care--package or process?

PMID- 9930251
TI  - Integrated management of childhood illness--a new approach to old diseases.

PMID- 9930252
TI  - Public health programmes, packages and processes.

PMID- 9930253
TI  - Detection and measurement of hypercholesterolaemia in South Africans attending
      general practitioners in private practice--the cholesterol monitor.
AB  - BACKGROUND: This paper reports data on the detection and management of
      hypercholesterolaemia in patients attending general practitioners in private
      practice in South Africa. METHODS: The frequency of cholesterol testing and the
      level at which active therapeutic intervention occurred at medical practices were
      monitored over a 2-year period. A sample of 200 medical practitioners was
      selected from private practices in major cities. Data on patients seen by the
      selected doctors during a 5-day monitoring period were recorded on a standardised
      form. RESULTS: 12,842 patients were seen by the 200 private practice GPs. More
      men (18.7%) than women (10.4%) had coronary heart disease (CHD), and their mean
      total cholesterol (TC) levels were 5.9 mmol/l and 6.0 mmol/l, respectively. Only
      3.1% of the patients were reported to have familial hypercholesterolaemia (FH)
      and 12.8% were reported to have a family history of CHD. Reported smoking rates
      were exceptionally high (77.5% of women and 64.4% of men). The most commonly
      prescribed group of lipid-lowering agents was HMG-CoA reductase inhibitors.
      CONCLUSIONS: Inadequate management of hypercholesterolaemia leaves many patients
      with a high risk of CHD mortality in South Africa. Appropriately investigated
      patients with hypercholesterolaemia should receive treatment to reduce
      cardiovascular disease using more effective TC control programmes than are
      currently used in South Africa.

PMID- 9930255
TI  - Year-round housedust mite levels on the Highveld.
AB  - OBJECTIVE: To determine the levels of the allergen DerPI, attributable to the
      house-dust mite (HDM) Dermatophagoides pteronyssinus. DESIGN: A four-season study
      conducted during 1994/95, sampling mattresses and carpets in the main bedrooms of
      suburban homes. SETTING: Thirty randomly selected homes in the Edenvale area,
      occupied by both black and white families living under similar socio-economic
      conditions in comparable environments. RESULTS: All homes tested positive for the
      allergen, and in 20% HDM levels exceeded levels recognised as 'safe' in terms of
      respiratory allergy, i.e. 2 micrograms/g of dust. Once mites were established in
      a home, they remained for months thereafter. The considerable seasonal variation
      recorded in HDM levels could not readily be explained. CONCLUSIONS: The HDM is
      extremely sensitive to minimal variations in microclimate. Its year-round
      presence is of concern on the Highveld. Infestation levels below 2 micrograms/g
      of dust, until recently considered the critical point for sensitisation, may be
      significant triggers of symptoms.

PMID- 9930256
TI  - What is the infant mortality rate in South Africa? The need for improved data.
AB  - OBJECTIVE: To review recent infant mortality and birth registration data in South
      Africa and to investigate geographical differences. OUTCOME MEASURES: Estimates
      of infant mortality rates, proportion of births not registered, and proportion of
      births recorded in health services. METHODS: 1. Published infant mortality data
      for South Africa were collated. Demographic data from national household surveys
      (1993 and 1994 October Household Surveys and the 1993 Poverty Survey by the
      Southern African Labour and Development Research Unit (SALDRU) at UCT) were
      analysed using the indirect method developed by Brass. 2. Birth registration data
      were analysed and compared with the estimated number of births to identify
      regions with greater under-registration. The number of births recorded in the
      health services was analysed by province in order to assess and explore
      alternatives within health authorities that could complement the existing system.
      RESULTS: 1. Published estimates of infant mortality for the period from 1990
      range from 40 to 71/1,000 births and estimates based on national household
      surveys conducted in this period from 11 to 81/1,000 births. 2. Completeness of
      birth registration in the nine provinces ranges from less than 10% in the Eastern
      Cape, North West and Northern Province to 60% in the Western Cape. An overall
      improvement from 19% to 60% could be achieved if births recorded through the
      health services were included in the vital registration system. CONCLUSIONS: The
      infant mortality rate in South Africa is not known with any certainty. The extent
      of completeness of the birth registration system was 19%, which indicates a need
      for urgent improvement in order to provide key health status indicators. This
      study indicates that there is some potential for improving the extent of birth
      registration if it could be facilitated through the health service. However, this
      alone would not achieve complete registration. RECOMMENDATIONS: Surveys will have
      to be relied upon until such time as routinely available statistics are accurate.
      The October Household Survey conducted annually by the Central Statistical
      Service as potentially an important source of health status information. It is
      imperative that either the design of the birth history questionnaire be improved
      or that it be replaced by a less frequent but more specialised demographic and
      health survey.

PMID- 9930254
TI  - Surgical resection for hepatocellular carcinoma in Cape Town--a clinical and
      histopathological study.
AB  - OBJECTIVE: Review of surgical resections performed for hepatocellular carcinoma
      (HCC) at our institution between 1990 and 1996, histology of resected specimens,
      and clinical outcome. DESIGN: Retrospective and prospective study of 14 patients
      who underwent resection for HCC. SETTING: The Hepatobiliary Unit and Liver
      Clinic, Groote Schuur Hospital, Cape Town. PATIENTS: Fourteen patients who
      underwent liver resections for HCC. INTERVENTIONS: Hepatic resections using
      prolonged vascular inflow occlusion. OUTCOME MEASURES: Clinical outcome and
      disease-free survival following resection. RESULTS: Fourteen patients (5.6% of
      the total number presenting with HCC) underwent liver resection for HCC at our
      institution between 1990 and 1996. There were 7 men, median age 40 years (range
      18-74 years). Only 2 patients were black, and only 1 of these patients had
      evidence of hepatitis B virus (HBV) infection in the liver. Extensive liver
      resections were often required. The mean (SD) ischaemic time was 81 (26) minutes
      and mean estimated blood loss was 938 (649) ml. During hospital admission, 1
      patient developed a minor bile leak that settled spontaneously, and 1 patient
      suffered a stroke and died. The mean hospital stay following operation was 12
      days (range 7-21 days). Disease-free patient survival at 1, 2 and 3 years was
      85%, 75%, and 62%, respectively. Histopathology of the resected specimens showed
      that 10 of 14 tumours had arisen in non-cirrhotic livers. Mean tumour size was
      10.6 (4.6) cm. Only 1 specimen showed the fibrolamellar variant of HCC.
      CONCLUSIONS: Only a small proportion of patients with HCC seen at Groote Schuur
      Hospital were eligible for resection, and only a minority of these had HBV
      associated 'African' HCC. The results of hepatic resection at our institution
      compare favourably with literature reports, despite the relatively large size of
      the tumours. It is of interest that most tumours arose in non-cirrhotic livers.
      There was no evidence of proliferation of 'oval-like' cells in non-neoplastic
      liver tissue.

PMID- 9930257
TI  - Characterisation of gastro-enteritis-associated adenoviruses in South Africa.
AB  - OBJECTIVE: To analyse adenovirus (Ad) numbers and types associated with
      paediatric gastro-enteritis in South Africa. SETTING: Gauteng, 1994-1996.
      METHODS: A total of 234 paediatric diarrhoeal stool samples were screened for Ad
      using commercial enzyme-linked immunosorbent assays (ELISAs). Adenoviral isolates
      were typed, where possible, using restriction enzyme analysis. RESULTS: Ad was
      detected in 23 (9.8%) specimens, of which 8 (34.8%) were found by subgroup F
      specific ELISA to contain Ad40 or 41. Six of these isolates were typed and 2
      could not be typed. Of the remaining 15 specimens, 2 isolates had restriction
      profiles that did not correspond with known Ads, while 2 were identified as Ad31
      and 1 as a subgroup C Ad. The remaining 10 specimens negative for Ad40/41 were
      non-cultivable and could not be typed. CONCLUSIONS: The high percentage of non
      cultivable Ads other than Ad40/41 is unusual, and may possibly indicate the
      prevalence of hexon variants of Ad40/41 or of emerging Ad types in South Africa.

PMID- 9930258
TI  - Sacrococcygeal germ-cell tumours--the Red Cross War Memorial Children's Hospital
      experience, 1980-1996.
AB  - OBJECTIVE: To document the experience of Red Cross War Memorial Children's
      Hospital in the treatment of sacrococcygeal germ-cell tumours. PATIENTS: Twenty
      seven patients with sacrococcygeal germ-cell tumours were treated in our hospital
      from 1980 to 1996. DESIGN: A retrospective review of these patients' records was
      undertaken. RESULTS: There were 19 female and 8 male patients. Seventeen (63%)
      presented in the neonatal period, 13 on the first day of life. Complete surgical
      resection of the tumour was achieved in all patients with mature or immature
      teratomas (20 patients) and in 2 neonates with malignant tumours. The first of
      these 2 neonates, with a malignant teratoma, was not given chemotherapy and
      remains well 10 years later. The second, with a yolk-sac tumour, also received no
      initial chemotherapy. He relapsed at the age of 9 months and was successfully
      treated with repeat excision and chemotherapy. All 5 patients first diagnosed
      after the age of 1 year had malignant tumours. These patients had incomplete
      surgical resection (3) or biopsy only (2), and 3 were successfully treated with
      chemotherapy. One patient relapsed with yolksac tumour after initial complete
      resection of a mature teratoma. She was successfully treated with repeat surgery
      and chemotherapy.

PMID- 9930259
TI  - Liver and renal and platelet counts after delivery in patients with severe pre
      eclampsia.

PMID- 9930260
TI  - Blood flow in the Zinn-Haller circle.

PMID- 9930261
TI  - Ploidy analysis in uveal melanoma.

PMID- 9930262
TI  - Identifying genes that cause disease: HLA-B27, the paradigm, the promise, the
      perplexity.

PMID- 9930263
TI  - Zinn-Haller arterial ring observed by ICG angiography in high myopia.
AB  - AIMS: To delineate the entire Zinn-Haller arterial ring angiographically in vivo.
      METHODS: 382 highly myopic eyes (210 patients) with refractive errors greater
      than -8.25 D were examined using indocyanine green (ICG) videoangiography. A
      control group of 80 eyes (40 patients) had refractive errors within plano +/- 3D.
      RESULTS: The Zinn-Haller ring was visible in 206 of 382 highly myopic eyes
      (53.9%) by ICG angiography. Although only a part of the Zinn-Haller ring was
      visible in 162 of 206 eyes, in the remaining 44 eyes it was observed almost
      completely around the optic nerve head. No anastomotic channels between lateral
      and medial short posterior ciliary arteries were filled by ICG angiography. In 22
      of the 44 eyes (50.0%) the Zinn-Haller ring was supplied by branches of the
      lateral and medial short posterior ciliary arteries; in seven eyes, it was
      supplied only by the lateral short posterior ciliary artery; and in seven eyes,
      it was supplied only by the medial short posterior ciliary artery. In none of the
      control subjects was the Zinn-Haller ring visible by ICG angiography.
      CONCLUSIONS: The Zinn-Haller ring observed by ICG angiography was not a complete
      collateral circle between lateral and medial posterior ciliary arteries. Also,
      the patterns in supply vessels to the Zinn-Haller ring varied. ICG angiography
      made possible the detailed observation of the Zinn-Haller ring in human eyes in
      vivo.

PMID- 9930264
TI  - Absence of hypertensive retinopathy in a Turkish kindred with autosomal dominant
      hypertension and brachydactyly.
AB  - BACKGROUND: A 60 member Turkish kindred with autosomal dominant hypertension,
      which cosegregates completely with brachydactyly and short stature, was studied.
      Affected people have severe hypertension and generally die of stroke by the age
      of 50. The hypertension closely resembles essential hypertension and,
      accordingly, the mechanisms of blood pressure elevation are unknown. The gene
      responsible was mapped to chromosome 12p. METHODS: All 29 affected family members
      underwent a basic physical examination and funduscopy. Other than markedly
      elevated blood pressures and the residua of stroke in a few subjects, the
      apparent lack of end organ damage was striking, including the normal appearing
      fundi. Five affected individuals were studied in a clinical research unit study.
      All underwent a complete ophthalmological examination. Fluorescein angiograms
      were obtained in three subjects. RESULTS: Systolic blood pressures ranged from
      170 to 250 mm Hg, while diastolic blood pressures ranged from 100 to 150 mm Hg in
      affected individuals. In all affected subjects, the fundi were only minimally
      altered or clinically normal. All three fluorescein angiograms were normal.
      Despite severe hypertension since childhood the patients showed no signs of
      hypertensive retinopathy. CONCLUSIONS: The absence of hypertensive retinopathy in
      this novel form of inherited hypertension is due to an altered structure of
      retinal arteriolar walls or some other protective mechanism. Since evidence of
      end organ damage is scarce in other organs as well, the protective mechanism
      appears to be generalised.

PMID- 9930265
TI  - Neuroretinal rim width ratios in morphological glaucoma diagnosis.
AB  - AIMS: To evaluate the inferior to temporal neuroretinal rim width ratio and
      superior to temporal rim width ratio as measures of rim shape for diagnosis of
      glaucoma. METHODS: Colour stereo optic disc photographs of 527 normal subjects,
      100 ocular hypertensive individuals with normal visual fields, and 202 open angle
      glaucoma patients with a mean perimetric defect of less than 10 dB were
      morphometrically evaluated. Eyes with an optic cup area of < 0.2 mm2 were
      excluded. RESULTS: In the normal subjects, inferior to temporal rim width ratio
      (1.67 (SD 0.53)) was significantly (p < 0.0001) higher than superior to temporal
      rim width ratio (1.56 (0.49)). Both ratios were significantly (p < 0.0001) higher
      the more vertically the optic disc was configured. In the normal eyes, both
      ratios were statistically independent of disc size, rim area, refractive error,
      age, and sex. With the differences being more marked for the inferior to temporal
      ratio than for the superior to temporal ratio, both rim width ratios were
      significantly (p < 0.005) lower in the ocular hypertensive group than in the
      normal group. Despite the high significance of the differences, diagnostic power
      of the inferior ratio and the superior ratio was 59% and 58%, respectively,
      indicating a marked overlap between the groups. CONCLUSIONS: Abnormally low
      inferior to temporal and superior to temporal rim width ratios can indicate
      glaucomatous optic nerve damage in some ocular hypertensive eyes. Being
      independent of optic disc size and ocular magnification, the rim width ratios may
      be taken as one among other variables for the ophthalmoscopic optic disc
      evaluation, taking into account, however, a pronounced overlap between normal
      eyes and ocular hypertensive eyes.

PMID- 9930266
TI  - Difficulty in performing everyday activities in patients with juvenile macular
      dystrophies: comparison with patients with retinitis pigmentosa.
AB  - AIMS: To ascertain the level of perceived difficulty experienced by patients with
      central vision loss due to juvenile macular dystrophies in the performance of
      everyday activities. A second objective was to compare their perceived difficulty
      with that of patients with retinitis pigmentosa (RP) with primarily peripheral
      vision loss. METHODS: 72 patients with Stargardt disease, cone dystrophy, or cone
      rod dystrophy who had visual acuities worse than 20/40 and normal peripheral
      visual fields rated themselves on their difficulty in the performance of 33
      activities encompassing a wide variety of everyday tasks. These findings were
      compared with the responses of 120 patients with typical RP or Usher syndrome
      type 2 who had visual acuities of 20/40 or better and peripheral visual field
      loss. RESULTS: The juvenile macular dystrophy group reported the greatest level
      of overall self perceived difficulty with activities involving central vision,
      and lesser and variable degrees of difficulty with items within the mobility,
      negotiating steps, driving, and miscellaneous categories. Consistent with these
      findings, there were highly significant correlations between subjects' rated
      performances of activities involving central vision and the clinical measures of
      vision, including visual acuity and size of central scotoma. There were fewer
      significant correlations between perceived performance of activities in the other
      categories and the clinical measures. In general, those activities that showed
      significant correlations with the clinical measures of vision for the patients
      with juvenile macular dystrophies also showed significant differences in the
      patterns of responses between the juvenile macular dystrophy group and the RP
      group. Those items which were not correlated with the clinical measures in the
      juvenile macular dystrophy group tended not to show significant differences in
      the response patterns between the two groups. CONCLUSION: These results provide
      insight into the types of perceived difficulties in performing tasks of everyday
      life in patients with these disorders which affect counselling of these patients.

PMID- 9930267
TI  - Pars plana vitrectomy with pars plana tube implantation in eyes with intractable
      glaucoma.
AB  - AIMS: Intractable glaucoma is glaucoma resistant to medical therapy and
      conventional surgical procedures. In this study, a planned surgical technique is
      discussed for controlling the increased intraocular pressure in selected cases
      with intractable glaucoma. METHODS: Total pars plana vitrectomy with pars plana
      tube implantation was performed in 17 eyes of 17 cases with intractable glaucoma.
      Patients with neovascular glaucoma were not included in this study. The mean age
      of these patients (seven men, 10 women) was 44.6 (SD 22.1) years and mean follow
      up period was 30.3 (15.5) months (range 4-71). Drainage implants with a disc were
      used in 16 cases, whereas, a tube with scleral buckle (Schocket surgery) was
      preferred in one case. An intraocular pressure below or equal to 20 mm Hg without
      any adjunctive medication or with only one type of antiglaucomatous drop was
      considered as an adequate operative outcome. RESULTS: 16 out of 17 eyes
      maintained adequate pressure control. Only three out of these 16 eyes required
      prophylactic antiglaucomatous medications. One patient underwent reoperation for
      pressure control. The most severe complications observed postoperatively were
      intravitreal haemorrhage (one case), choroidal detachment (one case), implant
      failure (one case), total retinal detachment (two cases), and corneal endothelial
      decompensation (five cases). CONCLUSION: Pars plana placement of drainage tube
      following pars plana vitrectomy should be considered as an alternative method for
      controlling increased intraocular pressures in selected patients with intractable
      glaucoma.

PMID- 9930268
TI  - Medium to long-term intraocular pressure control following small flap
      trabeculectomy (microtrabeculectomy) in relatively low risk eyes.
AB  - AIM: To determine the long-term efficacy of small flap trabeculectomy
      (microtrabeculectomy) in terms of intraocular pressure (IOP) control in
      relatively low risk eyes. METHOD: A review of a case series of small flap
      trabeculectomy procedures performed on 36 eyes from 36 patients with a minimum
      follow up of 24 months (mean 50.8). RESULTS: The mean (SD) intraocular pressures
      at presentation and preoperatively were 33.7 (7.5) and 24.6 (4.5) mm Hg. At 6
      months, 1, 2, 3, 4, 5, and 6 years the mean (n, SD) IOPs (mm Hg) of those eyes
      followed to each time point were 11.9 (36, 4.6), 12.6 (36, 4.7), 13.2 (36, 4.6),
      13.7 (29, 4.1), 13.2 (22, 4.0), 12.7 (15, 4.8), and 12.3 (8, 4.7) respectively.
      There was no significant difference in IOP levels at any of the analysis points
      by one way ANOVA. Kaplan-Meier analysis revealed survival rates of 80% at 4 years
      and 75% at 5 years when any postoperative IOP > 20 mm Hg is considered a failure,
      and 50% at 6 years when any IOP > 15 mm Hg is classed as a failure. CONCLUSION:
      Small flap trabeculectomy (microtrabeculectomy) is effective at reducing IOP in
      low risk glaucoma eyes with IOP control similar to previous reports of filtering
      surgery utilising larger scleral trapdoors.

PMID- 9930269
TI  - Acanthamoeba keratitis: multicentre survey in England 1992-6. National
      Acanthamoeba Keratitis Study Group.
AB  - AIM: To investigate the frequency, outcomes, and risk factors for acanthamoeba
      keratitis (AK) in England during the past 4 years. METHODS: An ophthalmologist in
      12 of the 14 regional health authorities (RHAs) coordinated identification of
      patients in their region presenting with AK between 1 October 1992 and 30
      September 1996. Clinical and postal patient questionnaire data were analysed.
      RESULTS: 243 patients (259 eyes) with an AK diagnosis were identified, equating
      to an annualised incidence of 0.14 per 100,000 individuals. UK resident patients
      for each year numbered 50, 71, 73, and 32 respectively. Among patients with
      sufficient data 170/237 (72%) were diagnosed early (within 30 days of
      presentation), 197/218 (90%) were treated with polyhexamethyl biguanide and/or
      chlorhexidine, and 40/243 (16%) underwent surgery. Visual acuities of 6/12 or
      better were achieved by 222/259 (86%) eyes, including 84 eyes of patients under
      review or lost to follow up. Non-contact lens (CL) wearers were associated with
      delayed diagnosis, increased need for surgery and a poorer visual outcome (only
      10/18 eyes, 56%, achieved 6/12 acuity). 225/243 (93%) patients were CL wearers,
      and 205/243 (84%) were soft CL (SCL) users. Among SCL user respondents,
      previously identified risk factors--swimming with CL (47/138, 34%), non-sterile
      CL rinsing (11/138, 8%), omitted disinfection (85/138, 62%), and chlorine release
      disinfection (65/138, 47%)--were identified for 125/138 (91%) patients.
      CONCLUSIONS: Earlier diagnosis and more effective medical therapy have improved
      the prognosis for most AK patients. The study demonstrates the highly preventable
      nature of the disease: 91% of the SCL wearers could have avoided the disease by
      refraining from inadvisable practices, and a marked fall in frequency was seen
      after intensive media attention to AK, possibly in conjunction with increasing
      penetrance of new CL products. Since the frequency of AK appears to be largely
      determined by the ever changing trends in CL use, continued monitoring is
      indicated.

PMID- 9930270
TI  - Confocal microscopy reveals persisting stromal changes after myopic
      photorefractive keratectomy in zero haze corneas.
AB  - AIMS: Micromorphological examination of the central cornea in myopic patients 8
      43 months after excimer laser photorefractive keratectomy (PRK), using the slit
      scanning confocal microscope. METHODS: Patients were selected from a larger
      cohort of individuals on the basis of full corneal clarity (haze grading 0 to +1;
      mean 0.3) and their willingness to participate in the study. 15 eyes of 10
      patients with myopic PRK (-4 to -11 D; mean 6.7) and an uneventful postoperative
      interval of 8-43 months (mean 26) were examined. Contact lenses had been worn by
      eight of the 10 patients for 4-11 years (mean 6.7) before surgery. Controls
      included the five untreated fellow eyes of PRK patients, 10 healthy, age matched
      volunteers without a history of ocular inflammation or contact lens wear, and 20
      patients who had worn rigid gas permeable (n = 10) or soft contact lenses (n =
      10) for 2-11 years. Subjects were examined with a real time flying slit, scanning
      confocal microscope using x25 and x50 objectives. RESULTS: In PRK treated
      patients and contact lens wearers, basal layer epithelial cells sporadically
      displayed enhanced reflectivity. The subepithelial nerve plexus was observed in
      all individuals, but was usually less well contrasted in the PRK group, owing to
      the presence of a very discrete layer of subepithelial scar tissue, which
      patchily enhanced background reflectivity. Within all layers of the stroma, two
      distinct types of abnormal reflective bodies were observed in all PRK treated
      eyes, but in none of the controls. One had the appearance of long (> = 50
      microns), slender (2-8 microns in diameter) dimly reflective rods, which
      sometimes contained bright, punctate, crystal-like inclusions, arranged linearly
      and at irregular intervals. The other was shorter (< 25 microns), more slender in
      form (< 1 micron in diameter), and highly reflective; these so called needles
      were composed of crystal-like granules in linear array, with an individual
      appearance similar to the bright punctate inclusions seen in rods, but densely
      packed. Both of these unusual structures were confined, laterally, to the ablated
      area, but were otherwise distributed throughout all stromal layers, with a clear
      predominance in the anterior ones. These rods and needles were observed in all
      PRK treated corneas, irrespective of previous contact lens wear. On the basis of
      qualitative inspection, the incidence of rods and needles did not appear to
      correlate with either the volume of tissue ablated or the length of the
      postoperative interval. In contact lens wearing controls, highly reflective
      granules, reminiscent of those from which the needles were composed, were found
      scattered as isolated entities throughout the entire depth and lateral extent of
      the corneal stroma, but rods and needles were never encountered. The corneal
      endothelium exhibited no obvious abnormalities. CONCLUSION: Confocal microscopy 8
      43 months after PRK revealed belated changes in the corneal stroma. These were
      manifested as two distinct types of abnormal reflective bodies, which had
      persisted beyond the stage when acute wound healing would have been expected to
      be complete. The clinical significance of these findings in the context of
      contrast visual acuity and long term status of the cornea is, as yet, unknown.

PMID- 9930271
TI  - Interobserver and intraobserver reliability of a classification scheme for
      corneal topographic patterns.
AB  - AIMS: To determine the interobserver and the intraobserver reliability of a
      published classification scheme for corneal topography in normal subjects using
      the absolute scale. METHOD: A prospective observational study was done in which
      195 TMS-1 corneal topography maps in the absolute scale were independently
      classified twice by three classifiers--a cornea fellow, an ophthalmic technician,
      and an optometrist. From these observations the interobserver reliability for
      each category and the intraobserver reliability for each observer were determined
      in terms of the median weighted kappa statistic for each category and for each
      observer. RESULTS: For interobserver reliability, the median weighted kappa
      statistic for each category varied from 0.72 to 0.97 and for intraobserver
      reliability the range was 0.79 to 0.98. CONCLUSION: This classification scheme is
      extremely robust and even in the hands of less experienced observers with minimal
      training it can be relied upon to provide consistent results.

PMID- 9930272
TI  - The conjunctiva in corneal epithelial wound healing.
AB  - BACKGROUND/AIMS: During the healing of corneal epithelial wounds with limbal
      involvement, conjunctival epithelium often migrates across the denuded limbus to
      cover the corneal surface. It is believed that, over a period of time,
      conjunctival epithelium covering the cornea assumes characteristics of corneal
      epithelium by a process referred to as conjunctival transdifferentiation. The
      purpose of this study was to examine, clinically, the fate of conjunctival
      epithelial cells covering the cornea and to assess the healing of corneal
      epithelial wounds when the conjunctival epithelium was removed or actively
      prevented from crossing the limbus and extending onto the cornea. METHODS: 10
      patients with conjunctivalisation of the cornea were followed for an average of
      7.5 months. Five patients in this group had their conjunctival epithelium removed
      from the corneal surface and allowed to heal from the remaining intact corneal
      epithelium. In another four patients with corneal epithelial defects, the
      conjunctival epithelium was actively prevented from crossing the limbus by
      mechanically scraping it off. RESULTS: The area of cornea covered by conjunctival
      epithelium appeared thin, irregular, attracted new vessels and was prone to
      recurrent erosions. Conjunctivalisation of the visual axis affected vision.
      Removal of conjunctival epithelium from the cornea allowed cells of corneal
      epithelial phenotype to cover the denuded area with alleviation of symptoms and
      improvement of vision. It was also established that migration of conjunctival
      epithelium onto corneal surface could be anticipated by close monitoring of the
      healing of corneal epithelial wounds, and prevented by scraping off conjunctival
      epithelium before it reached the limbus. CONCLUSION: This study shows that there
      is little clinical evidence to support the concept that conjunctival
      transdifferentiation per se, occurs in humans. "Replacement" of conjunctival
      epithelium by corneal epithelial cells may be an important mechanism by which
      conjunctival "transdifferentiation" may occur. In patients with partial stem cell
      deficiency this approach can be a useful and effective alternative to partial
      limbal transplantation, as is currently practised.

PMID- 9930273
TI  - Basal cell carcinoma of the eyelids and solar ultraviolet radiation exposure.
AB  - AIMS: To compare the distribution of eyelid basal cell carcinoma (BCC) with the
      relative ultraviolet radiation (UVR) exposure to different sites on the eyelids.
      METHODS: The location of BCC on the eyelids was allocated to one of seven
      regions. The UVR exposure was recorded with a polymer film attached to the
      eyelids at seven sites in a manikin and in human subjects. RESULTS: Localisation
      of the 329 tumours was mainly on the lower eyelids (225 tumours), and the medial
      canthal regions (87 tumours). There was no association between UVR doses at the
      seven sites of the eyelids and the location of BCCs. The UVR exposure was similar
      on the upper and lower eyelids, while the number of tumours on the lower eyelids
      outnumbered the upper lids by a factor of 13 (17 upper, 225 lower) CONCLUSION:
      UVR exposure only partially explains the aetiology of periorbital BCC.

PMID- 9930274
TI  - Clinical and scintigraphic comparison of silicone and polyvinylpyrrolidone coated
      silicone perforated plugs.
AB  - BACKGROUND/AIM: Isolated stenosis of the lacrimal punctum is a frequent cause of
      epiphora. Treatment relies on surgical opening or dilatation with bi- or
      monocanalicular prosthesis. Recently, silicone perforated punctum plugs (PPP)
      were proposed. The drawback with these silicone PPP was that secretions
      accumulate in the central orifice blocking the spontaneous flow of tears. A
      modification of the surface of the PPP using polyvinylpyrrolidone (PVP) was thus
      proposed. The aim was to compare silicone PPP with new PVP surface treated PPP.
      METHODS: A prospective study was conducted of 20 patients with dilatable stenosis
      of the lacrimal puncta who developed epiphora. Epiphora, tolerance, implantation
      of the PPP, and lacrimal drainage were evaluated using scintigraphy of the
      lacrimal ducts. RESULTS: The raw data and statistical analysis showed evidence of
      a superior performance of PVP surface treated PPP. CONCLUSION: Long term
      evaluation of the advantages or risks of PVP plugs and comparison with
      microsurgical punctoplasty are warranted.

PMID- 9930275
TI  - Split thickness buccal mucous membrane grafts and beta irradiation in the
      treatment of recurrent pterygium.
AB  - BACKGROUND: Pterygium is a common problem and after surgical removal may recur in
      up to 80% of cases, depending on the technique of primary excision. Recurrent
      pterygia can be aggressive and repeated excision may result in severe
      conjunctival scarring and shortening, resulting in insufficient conjunctiva to
      perform further grafting and lid surgery. When there is insufficient autologous
      conjunctiva, mucous membrane must be obtained from other sites. Full thickness
      buccal mucous membrane grafts have been described, but they may result in a beefy
      red appearance, with graft contraction and a poor tear film. METHOD: The use of
      split thickness buccal mucous membrane grafts is described in three patients with
      recurrent pterygium, two in combination with lamellar keratoplasty. beta
      Irradiation was used as adjuvant therapy in all cases. RESULTS: In all three
      cases an acceptable cosmetic appearance was achieved, with no recurrence of the
      pterygium, and a good range of eye movements. CONCLUSIONS: It is recommended that
      split thickness buccal mucosal grafts, combined with beta irradiation, should be
      considered in complex cases of pterygium recurrence when there is insufficient
      autologous conjunctiva and conjunctival shortening with restricted eye movements.

PMID- 9930276
TI  - Socioeconomic barriers to cataract surgery in Nepal: the South Asian cataract
      management study.
AB  - BACKGROUND: Previous studies have shown that, despite an increasing availability
      of cataract surgery, important socioeconomic barriers exist in the acceptance of
      surgery in many rural areas of south Asia. Nepal has developed a comprehensive
      national network of eye hospitals but the surgical coverage for the treatment of
      cataract blind is still low. AIMS: To determine the utilisation of cataract
      surgery and the level of physical and psychosocial impairment and the
      socioeconomic barriers to surgery in a group of non-acceptors of surgery.
      METHODS: Of 319 cataract patients identified in a field screening 96 non
      acceptors of surgery were interviewed 1 year after an offer to undergo surgery.
      The interview included questions on visual function, quality of life, and
      socioeconomic variables on acceptance of cataract surgery. The quality of life
      questionnaire was based on the field validated protocol addressing the impact of
      visual impairment on physical and psychosocial functions. The questionnaire was
      adapted to the local conditions after pretesting. Data were analysed by degree of
      visual impairment. RESULTS: Of 319 cataract patients identified only 45.5%
      accepted surgery, with men accepting surgery more readily than women (RR = 1.31;
      95% CI = 1.04-1.67) because of a significantly greater acceptance of surgery in
      men in the non-blind group. The acceptance rate was significantly higher in the
      blind group (RR = 1.74; 95% CI = 1.36-2.22) compared with those patients having
      impairment of vision and severe loss of vision. Of 96 non-acceptors interviewed
      only a further 13% accepted surgery after a second counselling. The most frequent
      reasons given for not accepting surgery were economic (48%) and logistical
      (44.8%) constraints followed by fear of surgery (33.3%) and lack of time (18.8%).
      Half of the subjects complained of problems with self care but only 10% needed
      help for their most basic every day activities. 17.7% said they needed help to
      visit neighbours and 26% needed help to attend the field or market. CONCLUSIONS:
      It was found that in this population with a majority of patients with severe
      vision loss and blind, even when offered transport and free surgery the
      utilisation of cataract surgery is below 60%. Medicine tends to be prescriptive
      based on technological advances that it is able to offer. Medical practice needs
      to develop a more holistic understanding of the needs of the communities
      cultivating a greater capability to analyse the role of cultural, social, and
      economic factors when planning medical services for the population.

PMID- 9930277
TI  - Anterior capsule contraction and intraocular lens dislocation in eyes with
      pseudoexfoliation syndrome.
AB  - AIMS: To examine the extent of anterior capsule contraction as well as
      intraocular lens (IOL) decentration and tilt following implant surgery in eyes
      with pseudoexfoliation syndrome (PE). METHODS: 53 eyes from 53 patients with PE
      and 53 control eyes from 53 age matched patients, undergoing phacoemulsification
      and implant surgery, were recruited. The anterior capsule opening area and the
      amounts of IOL decentration and tilt after undergoing continuous curvilinear
      capsulorhexis were measured using the Scheimpflug videophotography system at 1
      week and 1, 3, 6, 9, and 12 months postoperatively. RESULTS: The mean area of the
      anterior capsule opening in the PE group was significantly smaller than that in
      the control group at 1 month postoperatively and later. The percentage reductions
      in the PE group were approximately 25%, while they were less than 10% in the
      control group. The degree of IOL tilt was also larger in the PE group than in the
      control group. Five eyes (9.4%) in the PE group underwent a neodymium: YAG laser
      anterior capsulotomy, but none in the control group underwent a capsulotomy.
      CONCLUSIONS: The contraction of the anterior capsule opening was more extensive
      in the PE eyes than in the control eyes, thus resulting in a high Nd:YAG laser
      anterior capsulotomy rate. The IOL tilt was also greater in the PE eyes than in
      the control eyes.

PMID- 9930278
TI  - DNA ploidy pattern in choroidal melanoma: correlation with survival. A flow
      cytometry study on archival material.
AB  - BACKGROUND/AIMS: Paraffin embedded samples have provided an important source of
      material for retrospective cytofluorimetric studies, useful in establishing the
      predictive value of DNA content measurements. The aim of this study was to
      investigate the incidence and type of aneuploidy in choroidal malignant melanomas
      (CMM) and the significance in the clinical outcome (median follow up 55 months).
      METHODS: DNA content was quantified by flow cytometry in 61 CMM from archival
      material. Non-tumour ocular tissue was used as the reference diploid standard.
      Cases in which the coefficient of variation (CV) of the diploid peak was > 8%
      were excluded. The CMM were classified as spindle A, spindle B, mixed spindle and
      epithelioid, epithelioid, and necrotic. RESULTS: The frequency of the aneuploid
      DNA pattern was 38%. Necrotic tumours showed a worse clinical outcome independent
      of the ploidy pattern. Spindle A tumours were found to be diploid. Spindle B and
      mixed tumours showed a prevalent diploid and near diploid aneuploid pattern (DI <
      1.3), yet aneuploidy was not correlated with a worse prognosis. The epithelioid
      tumours were prevalently diploid. However, 83% of the aneuploid tumours were
      hypodiploid (DI < 0.95), and showed the worst prognosis. CONCLUSION: These
      results indicate that increasing DNA abnormalities in CMM, especially in the
      epithelioid histotype, were associated with an increasing mortality.

PMID- 9930279
TI  - Ultrasound enhanced thrombolysis in experimental retinal vein occlusion in the
      rabbit.
AB  - AIMS: To investigate if it was possible to lower the dose of streptokinase and
      maintain an effective thrombolysis by adding pulsed low energy ultrasound.
      METHODS: 53 retinal veins in 27 rabbits were occluded by rose bengal enhanced
      laser treatment. Six rabbits were treated with streptokinase (50,000 IU/kg), 10
      rabbits were treated with a low dose of streptokinase (25,000 IU/kg), and 11
      rabbits were treated with a low dose of streptokinase (25,000 IU/kg) and pulsed
      ultrasound during 1 hour. Fluorescein angiography was performed immediately
      before the thrombolytic treatment and after 12 hours. RESULTS: In the group
      treated with streptokinase (50,000 IU/kg) all vessels were open. In the group
      that was given streptokinase (25,000 IU/kg), 21% of the vessels were open. In the
      group that was treated with streptokinase (25,000 IU/kg) and ultrasound, 64% of
      the vessels were open. The difference between groups 2 and 3 is statistically
      significant (p = 0.011) CONCLUSION: Adding pulsed low energy ultrasound makes it
      possible to lower the dose of streptokinase while maintaining a good thrombolytic
      effect.

PMID- 9930280
TI  - Alternative therapies in exudative age related macular degeneration.

PMID- 9930281
TI  - Congenital toxoplasma chorioretinitis transmitted by preconceptionally immune
      women.

PMID- 9930282
TI  - Shinty and ocular trauma in north west Scotland.

PMID- 9930283
TI  - Ultrastructural alterations in the stroma adjacent to non-inflammatory corneal
      perforations associated with long standing rheumatoid arthritis.

PMID- 9930284
TI  - Overt chorioretinitis after patient acquired toxoplasmosis in an immunocompetent
      subject.

PMID- 9930285
TI  - Anterior segment complications of indirect diode laser in diabetic patients.

PMID- 9930286
TI  - Adverse outcome after multiple pregnancy.
AB  - There is increasing interest in the outcomes of multiple pregnancies as their
      numbers rise, mainly owing to advances in fertility-enhancing techniques. In
      addition, the numbers of multiple births surviving the perinatal period is
      increasing with the increasing survival of very tiny babies. In order to
      investigate these outcomes or to evaluate procedures that may improve them, it is
      important to consider a number of methodological issues that affect the
      comparability of data both between and within populations. How a birth and a
      multiple birth are defined, data sources, whether multiple pregnancies or
      individual births are being counted and the identification of multiple gestations
      by zygosity and chorionicity will all affect the reported outcome rates. In light
      of this, perinatal mortality and neurodevelopmental disabilities are examined as
      adverse outcomes of multiple pregnancies.

PMID- 9930287
TI  - Screening for fetal abnormalities in multiple pregnancies.
AB  - Multiple gestations account for 1-2% of all pregnancies but contribute
      disproportionately to the incidence of both perinatal loss and fetal structural
      abnormalities. Ultrasound examination provides essential information about
      screening for, and the management of, such defects, including accurate
      determination of chorionicity, assessment of risk, invasive testing and selective
      termination if appropriate.

PMID- 9930288
TI  - The consequences of monochorionic placentation.
AB  - Monochorionic (MC) placentation occurs in two-thirds of monozygous twins and
      approximately 0.3% of all spontaneous conceptions. Vascular anastomoses within
      the placenta allow intertwin transfusion to occur, which is in most cases a
      normal event. However, imbalance in this flow may lead to the clinical sequelae
      observed, with acute, chronic or reverse intertwin transfusion. Acute transfusion
      describes the events following the death of one of an MC twin pair in utero, with
      an approximately 1 in 4 chance of demise or neurological damage in the co-twin.
      Chronic intertwin transfusion, otherwise termed feto-fetal transfusion syndrome,
      arises following the gradual flux of blood from one twin (the donor) to its
      sibling fetus (the recipient). The ensuing polyhydramnios places the pregnancy at
      risk of preterm amniorrhexis and/or labour, notwithstanding the specific sequelae
      seen in these fetuses following chronic in utero insult. Reverse transfusion
      describes the most bizarre form of intertwin transfusion: acardiac twinning.
      Retrograde perfusion of one of the twins with deoxygenated blood leads to the
      formation of a non-viable acardiac parasite and a 'pump twin' struggling to
      maintain the cardiac output required to perfuse both twins.

PMID- 9930289
TI  - Prediction of preterm labour in multiple pregnancies.
AB  - Various methods of predicting preterm labour in both singleton and multiple
      pregnancies have been studied including risk scoring systems, home uterine
      activity monitoring, cervical assessment and biochemical methods. In practice,
      risk scoring systems for preterm delivery perform poorly. Consensus in the
      literature regarding the usefulness of home uterine activity monitoring is
      lacking and well designed randomized controlled trials are required. Transvaginal
      ultrasound assessment of the cervix appears to have a role to play in the
      prediction of preterm labour. The presence of IFN in cervicovaginal fluid in the
      late second and early third trimesters is an important risk factor for preterm
      labour in asymptomatic women with multiple pregnancies. Preterm labour may be
      mediated in part by inflammatory cytokines. The measurement of these inflammatory
      cytokines in cervical secretions may also prove helpful in the prediction of
      preterm labour. It is anticipated that an improved ability to predict preterm
      labour in both singleton and multiple pregnancies will depend on increasing
      understanding of the condition's pathophysiology.

PMID- 9930290
TI  - Prevention of preterm birth in multiple pregnancy.
AB  - Preterm birth is the greatest threat to the infants in a multiple pregnancy. This
      chapter focuses on strategies that aim to prevent preterm birth and concentrates
      on the evidence derived from randomized clinical trials and systematic review of
      randomized clinical trials. The options to avoid a multiple pregnancy are briefly
      considered. Interventions that aim to prolong pregnancy, including prophylactic
      cervical cerclage, prophylactic tocolysis, home uterine activity monitoring and
      hospitalization for bed rest, are critically appraised, as are interventions that
      aim to improve the outcome of preterm birth. Interventions that require
      additional evaluation are highlighted.

PMID- 9930291
TI  - Doppler ultrasound in multiple pregnancies.
AB  - This chapter aims to provide a current review of the use of Doppler ultrasound in
      the management of multiple pregnancies. OVID and Medline searches were
      undertaken. Randomized controlled trials, where available, were assessed by the
      Cochrane Review Manager (RevMan-version 3.0). The specific multiple pregnancy
      problems of fetal growth restriction (FGR), twin reversed arterial perfusion
      sequence and twin-twin transfusion syndrome (TTTS) were also reviewed.
      Historically, controlled and randomized controlled trials show a promising
      reduction in perinatal mortality in twin pregnancies where Doppler ultrasound is
      used. However, the numbers are small and further trials are recommended. In those
      twin pregnancies in which there is FGR as a result of placental dysfunction,
      Doppler ultrasonography will show intertwin discordancy. In those twin pairs
      where development is complicated by TTTS, there is often discordant fetal size,
      with concordant fetal Doppler results. Thus Doppler ultrasound appears to be
      useful in the management of twin pregnancies and in delineating those complicated
      by FGR and TTTS.

PMID- 9930292
TI  - Delivery of twins.
AB  - The delivery of twins presents considerable challenges to the obstetric team,
      particularly in terms of decision-making, technical skills required and the need
      to respond quickly to changing circumstances. There is a serious lack of sound
      evidence upon which to base decisions concerning the method of delivery of twins.
      The trend towards the routine use of caesarean section is not supported by
      evidence of improved outcome for the infants, while maternal outcome is
      compromised. Specific circumstances that may have a bearing on the need for
      caesarean section include gestational age, presentation of the twins and
      chorionicity/amnionicity. Caesarean section does not eliminate the chance of
      fetal trauma during delivery, particularly for premature twins. The techniques of
      twin delivery, whether vaginal or by caesarean section, require thorough
      preparation for all possible eventualities, and skilled teamwork. Particular
      attention should be paid to emotional needs during labour, birth and afterwards,
      of the parents of twins.

PMID- 9930293
TI  - Obstetric management of high-order multiple pregnancies.
AB  - High-order multiples are increasingly common as a result of assisted reproductive
      technologies and represent pregnancies at exceptional risk. This article
      discusses the antepartum management of high-order multiples, which has in general
      been highly individualized and poorly studied. Care for high-order multiples
      should include preterm birth prevention education, the frequent assessment of
      maternal symptoms and cervical status by a consistent provider, individualized
      modification of activity, attention to maternal nutrition, ultrasonography for
      the assessment of fetal anatomy and intra-uterine growth and anticipation of
      maternal complications. Interventions such as prophylactic cerclage, uterine
      activity monitoring, prophylactic tocolysis or hospitalization have not improved
      outcome when used routinely, and guidelines for selective use will be presented.
      Specialized care for high-order multiples should be directed at identifying
      congenital anomalies, maximizing fetal growth and preventing early preterm birth,
      the effect of which will be to improve perinatal outcome for these exceptional
      pregnancies.

PMID- 9930294
TI  - Strategies to prevent multiple pregnancies in assisted conception programmes.
AB  - All assisted conception techniques are associated with an increase in the
      multiple pregnancy rate. Iatrogenic multiple births are increasing as the use of
      these technologies expands. The cornerstone of safe ovulation induction is
      careful ultrasound monitoring, with cancellation of cycles if excessive ovulation
      is expected. In in vitro fertilization (IVF) cycles, the main determinant of
      multiple pregnancy risk is the number of embryos replaced. The current move in
      IVF clinics is to reduce the risk of multiple pregnancy by reducing the number of
      embryos transferred. We would suggest a maximum of two embryos transferred to
      women under, for example, 39 years of age. Women of 39 years or over have a
      reduced chance of embryo implantation; they should be allowed the transfer of up
      to three embryos (the UK legal maximum).

PMID- 9930295
TI  - Multifetal pregnancy reduction.
AB  - Multifetal pregnancy reduction (MFPR) has become a mainstay of infertility
      therapy as its development has allowed physicians to become more aggressive in
      treating patients resistant to more conservative therapies. Over the course of
      the past decade, MFPR has become practised in a limited number of tertiary
      specialty centres, which have improved its performance and very substantially
      lowered its risks. The majority of physicians performing MFPR employ a
      transabdominal needle injection of potassium chloride into the fetal thorax.
      Risks for pregnancy losses of patients starting with triplets and/or quadruplets
      reduced to twins have improved over the past decade and are not substantially
      different from those in patients whose pregnancy began as twins. There have been
      no substantiated risks of coagulopathies or damage to surviving fetuses.

PMID- 9930296
TI  - Immunotherapy of cancer with dendritic cell-based vaccines.

PMID- 9930297
TI  - Comparison of four strategies for tumour vaccination in the B16-F10 melanoma
      model.
AB  - We have compared four cell-based tumour vaccine strategies in prevention
      experiments using the B16-F10 melanoma model. Two of these are thought to favour
      the direct antigen presentation pathway (B16-F10 expressing B7.1 and hybrids made
      between B16-F10 cells and macrophages) and the other two strategies are thought
      to act by an indirect pathway of presentation (allogeneic tumour cells and
      autologous tumour cells combined with a powerful adjuvant (Provax-IDEC
      Pharmaceuticals)). Only the two latter vaccines promoted antitumour activity,
      whereas the vaccines consisting of B7.1-expressing tumour cells or the hybrid
      vaccine failed to provide any antitumour activity. Recently human trials have
      commenced using transfection of the B7.1 molecule, as well as employing the
      hybrid technology to make tumour-B cell hybrids or tumour and dendritic cell
      hybrids. Our results suggest that these approaches could be disappointing in the
      clinics if not optimised.

PMID- 9930298
TI  - A comparison of in vivo gene delivery methods for antisense therapy in ligament
      healing.
AB  - To determine the most efficient in vivo delivery method of oligonucleotides for
      antisense therapy in ligament healing, fluorescence-labelled phosphorothioate
      oligodeoxynuleotides (ODN) were introduced into 12 rabbit ligament scars 2 weeks
      after injury using haemagglutinating virus of Japan (Sendai virus: HVJ)
      conjugated liposomes. We compared the efficiency of cellular uptake of
      fluorescence as a percentage of all cells in each scar using three delivery
      procedures: (1) direct free-hand injection into the ligament scar using a
      conventional syringe; (2) systematic direct sca injection using a repeating 10
      microliters dispenser and a square mesh grid system; and (3) injection into the
      feeding (femoral) artery. Results showed that there was a significant difference
      in fluorescence uptake by scar cells on day 1 after injection between the three
      delivery methods: (1) direct free-hand, 9.7 +/- 7.6% (average +/- s.d.); (2)
      systematic direct, 58.4 +/- 15.9%; and (3) intra-arterial, 0.2 +/- 0.1%.
      Systematic direct injection was most efficient and it resulted in 25.9 +/- 13.0%
      of scar cells being labeled at 7 days after transfection. We then introduced
      antisense ODN for the rabbit proteoglycan, decorin, into ligament scars with this
      delivery method and confirmed a significant inhibition of decorin mRNA expression
      in antisense-treated scar tissues in vivo both at 2 days (42.3 +/- 14.7% of sense
      control +/- s.d.; P < 0.0025) and 3 weeks (60.5 +/- 28.2% of sense control +/-
      s.d.; P < 0.024) after treatment, compared with sense ODN-treated scars. Decorin
      was significantly suppressed also at protein level in antisense-treated scars at
      4 weeks (66.6 +/- 35.7% of sense control +/- s.d.; P < 0.045) after treatment.
      These results demonstrate that in vivo transfection efficiency in ligament scars
      is 'delivery system dependent' and that introduction of antisense ODN for the
      small proteoglycan, decorin, with this delivery method can lead to significant
      suppression of its expression over 3 weeks both at mRNA and protein levels. Thus,
      an effective model for the potential manipulation of scar composition and quality
      in ligament healing has been established.

PMID- 9930299
TI  - Potentiation of E7 antisense RNA-induced antitumor immunity by co-delivery of IL
      12 gene in HPV16 DNA-positive mouse tumor.
AB  - Down-regulation of oncogene expression by antisense-based gene therapy has been
      extensively studied, and in some cases, therapeutic effects have been
      demonstrated. We have previously shown that down-regulation of HPV16 E6 and E7
      gene expression inhibited HPV DNA-positive C3 mouse tumor growth. Although not
      all of the tumor cells were transfected by pU6E7AS plasmid, complete tumor
      regression was achieved if the tumor size was small at the start of therapy in a
      syngeneic host. This suggests that some other antitumor mechanisms may be
      involved in addition to the direct down-regulation of HPV16 E7 oncogene
      expression by the antisense effect of E7AS. In the current study, we demonstrated
      that E7AS induces tumor cell apoptosis. More importantly, a strong antitumor
      immune response was elicited in the pU6E7AS-treated and tumor-regressed mice.
      There was no tumor growth after rechallenging the tumor-regressed mice with 1
      million C3 cells. This E7AS-induced antitumor immune response was augmented by co
      delivery of mIL-12 cytokine gene. The combination therapy strategy resulted in
      complete regression of 26 of 28 (93%) tumors. Only 12 of 31 (38%) tumors from the
      group treated with pU6E7AS alone and 14 of 28 (50%) tumors from the group treated
      with pCMVmIL-12 alone had completely regressed. Complete regression was also
      demonstrated in tumors located 1 cm from the treated tumors, which indicates that
      a systemic antitumor effect was induced by E7AS and mIL-12. Immunohistochemistry
      demonstrated that a significant amount of CD4+ and CD8+ cells infiltrated into
      tumors treated with pU6E7AS, pCMVmIL-12 and pU6E7AS+pCMVmIL-12. These data
      indicate that host immunity is an important factor for antisense-based gene
      therapy approach which can be further enhanced by combination with cytokine gene
      therapy.

PMID- 9930300
TI  - Efficient transfer of oligonucleotides and plasmid DNA into the whole heart
      through the coronary artery.
AB  - Several of the current techniques for transfer of both oligonucleotide and
      plasmid DNA into the myocardium are impaired by low efficiency and toxicity. To
      improve gene transfer techniques, especially into the whole heart, a gene
      transfer method involving liposome in conjunction with a viral envelope (HVJ
      liposome) was essayed as an alternative. FITC-labeled oligonucleotide (F-ODN) and
      the cDNA of beta-galactosidase (beta-gal) were introduced into the myocardium by
      coronary infusion of HVJ-liposome during cardioplegic arrest of adult Sprague
      Dawley rat hearts. Then, transfected heart was ectopically transplanted into
      another rat abdomen of the same strain to maintain the transfected heart long
      enough to allow for protein synthesis. After 3 days of transfection, transfected
      heart was excised and the efficiency of gene transfection was evaluated. FITC was
      detected in the nuclei of more than 70% of the myocytes and endothelial cells
      both in the epicardium and endocardium. beta-Gal was expressed in the cytosol of
      more than 50% of the myocytes. beta-Gal expression was demonstrated by Western
      blotting analysis at day 3 after transfection and continued for at least 14 days.
      No significant histological damage of the myocardium or leakage of CPK were
      detected in the rats transfected by the HVJ-liposome method. These results
      clearly demonstrate that the hearts were efficiently transfected both by
      oligonucleotide and plasmid DNA as a result of coronary infusion of HVJ-liposome
      during cardioplegic arrest. This thus appears to be an efficient method for gene
      transfer into the whole heart, providing a new tool for research and therapy for
      heart diseases.

PMID- 9930301
TI  - Gene transfer vectors derived from equine infectious anemia virus.
AB  - Equine infectious anemia virus (EIAV) is a lentivirus in the retrovirus family of
      viruses. Replication-defective EIAV vectors have been constructed that encode
      bacterial puromycin-N-acetyl transferase and E. coli beta-galactosidase. These
      vectors could be prepared with titers greater than 10(5) infectious units/ml and
      were able to act as vehicles to carry genes into cultured human cells. In
      addition, stable helper cell lines were created by modifying human 293 cells to
      express EIAV proteins. Unlike retroviral vectors based on murine leukemia virus,
      EIAV lentiviral vectors transduce nondividing (aphidicolin-arrested) cells. These
      properties make EIAV vectors promising gene transfer vehicles.

PMID- 9930302
TI  - Liposomes enhance delivery and expression of an RGD-oligolysine gene transfer
      vector in human tracheal cells.
AB  - Nonviral gene delivery systems consist predominantly of lipoplexes or receptor
      targeting and nontargeting polyplexes. We examined integrin-mediated gene
      delivery using an Arg-Gly-Asp/oligo-L-lysine ([K]16RGD) cyclic peptide and
      investigated its gene transfer efficiency when associated with a cationic
      liposome. We demonstrated that human cystic fibrosis and noncystic fibrosis
      tracheal epithelial cells in culture express integrins that recognise the RGD
      integrin-binding motif. We found a 10-fold (P < 0.01) increased expression of a
      luciferase encoding plasmid in these cells when complexing the plasmid to the
      [K]16RGD peptide as compared with plasmid alone. This increase was specific to
      the [K]16RGD peptide since neither a [K]16RGE nor a [K]16 peptide gave a
      comparable increase. Expression was further enhanced 30-fold (P < 0.01) with
      lipofectamine and the ratio of DNA/peptide/lipofectamine was critical for
      specificity and expression. Fluorescence and radioactive labelling of the complex
      showed that the [K]16RGD peptide increased the endocytic uptake of DNA into
      cells. The cell association of both DNA and peptide increased even further with
      lipofectamine. Confocal microscopy showed that the [K]16RGD peptide and the DNA
      internalised together within 30 min and localised to vesicles in the perinuclear
      region. These results show that an integrin-binding ligand can deliver genetic
      material to airway cells and that a cationic liposome can enhance the efficacy of
      this nonviral vector system.

PMID- 9930303
TI  - Successful use of a plant gene in the treatment of cancer in vivo.
AB  - A new strategy for cancer gene therapy has been developed using a plant gene
      which encodes the enzyme, linamarase, that hydrolyzes the cyanogenic glucoside
      substrate, linamarin, into glucose, acetone and cyanide. Retroviral vectors that
      carry linamarase as a potential killer-suicide gene cause a marked sensitization
      to the innocuous substrate, linamarin, followed by cell death. We show that the
      system can eradicate very large intracerebral gliomas in vivo helped by a cyanide
      bystander effect. Animals showing a total regression of the tumor by magnetic
      resonance imaging (MRI), do not show other appreciable toxic effects.

PMID- 9930304
TI  - Polyethylenimine-mediated transfection of human monocytes with the IFN-gamma
      gene: an approach for cancer adoptive immunotherapy.
AB  - Human monocytes (Mo) and monocyte-derived macrophages (MdM) are major effectors
      in host defense systems against cancer. Their antitumoral activity is dependent
      upon two processes: recruitment and activation. One of the most powerful
      activators for these cells is recombinant human IFN-gamma (rhIFN-gamma). However,
      when the potential of activated rhIFN-gamma was evaluated in clinical trials by
      ex vivo adoptive cellular immunotherapy protocols, the major problem was the
      short duration of ex vivo activation by rhIFN-gamma. Thus repeated injections
      were required to obtain a clinical response. To overcome this limitation we have
      developed a gene transfer protocol with IFN-gamma cDNA and polyethylenimine so as
      to obtain an efficient, long-lasting autocrine cytocidal activation in
      transfected human Mo/MdM. We show, by clonogenic assays, that efficient
      transfection and tumoricidal activity can be obtained by this method in human
      monocyte populations. Although the proposed model must be improved before
      clinical use, IFN-gamma producing monocytes have potential for adoptive
      immunotherapy.

PMID- 9930305
TI  - Development of herpes simplex virus replication-defective multigene vectors for
      combination gene therapy applications.
AB  - Some gene therapy applications will require simultaneous expression of multiple
      gene products to achieve a therapeutic effect. In this study we describe the
      generation and characterization of replication incompetent herpes simplex virus
      type 1 (HSV-1) vectors (HX86Z or HX86G) carrying distinct and independently
      regulated expression cassettes for five transgenes (hIL-2, hGM-CSF, hB7.1, HSV-tk
      and lacZ or hIFN gamma). The transgenes, representing 12 kb of DNA sequence, were
      recombined into separate loci of a single mutant virus vector deleted for 11.6 kb
      of vector sequences representing portions of nine viral genes, ICP4, ICP22,
      ICP27, ICP47, UL24, UL41, UL44, US10 and US11. Deletion of the immediate--early
      genes ICP4, ICP22 and ICP27 substantially reduced vector cytotoxicity, prevented
      early and late viral gene expression and left intact MHC class I antigen
      expression. Simultaneous expression of multiple transgenes was obtained for up to
      7 days in primary human melanoma cells with peak expression at 2-3 days after
      infection. The transgenes were chosen for their potential to function
      synergistically in tumor destruction and vaccine gene therapy applications, but
      the method and vector employed could be applied to other multigene therapy
      strategies. This study demonstrates the potential for engineering large transgene
      capacity DNA viruses such as HSV-1 for expression of multiple transgenes.

PMID- 9930306
TI  - Enhanced gene expression in mouse lung by prolonging the retention time of
      intravenously injected plasmid DNA.
AB  - The effect of retention time of plasmid DNA in mouse lung on the level of
      transgene expression after intravenous administration was examined. Using CMV
      driven expression system with luciferase gene as a reporter and preinjection of
      free cationic liposomes into the animal as means of manipulating the retention
      time of plasmid DNA, we demonstrated that naked plasmid DNA is effective in
      transfecting cells in the lung by intravenous administration. An increase in DNA
      retention time in the lung results in a higher level of gene expression.
      Liposomes composed of cationic lipids with alkyl chains exhibited better activity
      than cholesterol-based cationic liposomes to retain the plasmid DNA in the lung.
      The level and patterns of gene expression obtained appeared similar to those seen
      in animals transfected by DNA-liposome complexes. These results suggest that
      prolonging the exposure time of DNA to the target cells in vivo may be an
      important strategy in achieving a high level of gene expression. Our data also
      introduce a possibility that the function of cationic liposomes in lipoplex
      mediated transfection in vivo is to extend the interaction time of DNA with the
      cells.

PMID- 9930307
TI  - Safety study and characterization of E1A-liposome complex gene-delivery protocol
      in an ovarian cancer model.
AB  - A phase I clinical trial of E1A-liposome complex is currently ongoing in patients
      with HER-2/neu-overexpressing breast or ovarian cancers. To optimize the E1A
      liposome complex for a further stage of clinical trial, several aspects of the
      current protocol have been examined in an animal model. In the orthotopic ovarian
      cancer model, different doses of lipid in the the E1A-liposome complex, which is
      currently used in clinical trials, were tested for the in vivo gene-transfer
      efficacy and tumor-suppression function. A lowered lipid dose--1/13 of the
      previous amount--produced gene expression level and E1A tumor-suppression
      efficacy similar to that of the original protocol. Mini-E1A, an E1A construct
      without its immortalization domain and yet capable of repressing HER-2/neu, was
      proved to be as potent as E1A in suppressing tumor development in vivo. These
      changes in the E1A-liposome complex will significantly reduce any potential
      adverse effects caused by lipid vector and E1A DNA. To examine further whether
      residual E1A DNA may still exist in normal organs after the E1A-liposome
      treatment, PCR was used to detect E1A DNA in mice that survived for 1 1/2 years
      after the last treatment. E1A DNA was detected only in the lungs and kidneys, but
      not in livers, hearts, spleens, brains, uterus or the ovaries. Furthermore,
      resistance of the E1A DNA extracted from tissues to the digestion of Dpnl
      restriction enzyme, which can cleave the methylated E1A plasmid DNA generated by
      methylation-competent bacteria, suggested integration of E1A DNA into the
      chromosome of the lungs and kidneys. Experimental results presented here provide
      important information for safety concerns and for the design of future phase II
      and phase III trials.

PMID- 9930308
TI  - Retroviral transfer and long-term expression of human cytidine deaminase cDNA in
      hematopoietic cells following transplantation in mice.
AB  - The chemotherapeutic effectiveness of cytosine nucleoside analogues used in
      cancer therapy is limited by their dose-dependent myelosuppression. A way to
      overcome this problem would be to insert the drug-resistance gene, cytidine
      deaminase (CD), into normal hematopoietic cells. CD catalyzes the deamination and
      pharmacological inactivation of cytosine nucleoside analogues, such as cytosine
      arabinoside (Ara-C). The objective of this study was to determine if we could
      obtain long-term persistence and expression of proviral CD in hematopoietic cells
      following transplantation of CD-transduced bone marrow cells in mice. Murine
      hematopoietic cells were transduced with an MFG retroviral vector containing CD
      cDNA and transplanted into lethally irradiated mice. The recipient mice were
      administered three courses of 10-15 h i.v. infusions of Ara-C (75-110 mg/kg).
      Blood, marrow and spleen samples were obtained and analyzed for CD proviral DNA
      by PCR, CD activity by enzyme assay, and drug resistance to Ara-C by clonogenic
      assay. We detected the presence of the CD proviral DNA in most of the samples
      examined. Approximately 1 year after transplantation several mice showed
      increased expression of CD activity in these tissues and some mice displayed
      signs of Ara-C resistance. These data demonstrate that persistent in vivo
      expression of proviral CD can be achieved in transduced hematopoietic cells and
      indicate some potential of this gene for chemoprotection to improve the efficacy
      of cytosine nucleoside analogues in cancer therapy.

PMID- 9930309
TI  - Gene transfer of tissue inhibitor of metalloproteinase-2 inhibits
      metalloproteinase activity and neointima formation in human saphenous veins.
AB  - Metalloproteinases (MMPs) are implicated in neointima formation and hence vein
      graft failure. Gene transfer to elevate local levels of tissue inhibitor of
      metalloproteinases (TIMPs) is therefore a potential treatment. In this study, we
      have used lumenal application of a replication-defective recombinant adenovirus
      to overexpress TIMP-2 and observe the effects on neointimal thickening in a well
      characterised human saphenous vein organ culture model. Increased TIMP-2
      expression was localised to lumenal surface cells but nevertheless increased
      total functional TIMP-2 secretion after 14 days culture from 4.0 +/- 2.0 to 21.8
      +/- 2.9 ng/mg wet weight/day (P < 0.05, n = 3). In situ zymography revealed a
      marked inhibition of gelatinolytic activity by TIMP-2 gene transfer throughout
      the vein segments. Neointima formation and neointimal cell numbers were reduced
      79% and 71%, respectively (P < 0.05; n = 8). TIMP-2 overexpression had no effect
      on smooth muscle cell proliferation, secretion of pro-MMP-2 or -9 and did not
      inhibit the processing of pro-MMP-2 to its active form. Our data indicate that
      TIMP-2 overexpression reduces neointimal thickening, primarily by inhibiting MMP
      activity and hence smooth muscle cell migration.

PMID- 9930310
TI  - Co-injection of adenovirus expressing CTLA4-Ig prolongs adenovirally mediated
      lacZ reporter gene expression in the mouse retina.
AB  - There is growing interest in gene delivery to the eye in order to develop gene
      therapy for the many ocular disorders which may be amenable to this approach. To
      date, recombinant adenoviruses (AV) have been the main vector used for gene
      delivery to anterior and posterior segments in animal models. As with delivery to
      other organs, immune responses to vector and transgene limit the duration of
      expression in the eye. Using an E1-deleted adenoviral vector carrying a lacZ
      reporter gene, we have previously demonstrated that a T cell-mediated immune
      response reduces the level of intra-ocular transgene expression over time and
      limits it to around 3 weeks in mice. This report describes a strategy for
      prolonging gene expression by blocking the B7-CD28 interactions between antigen
      presenting cells (APC) and T cells in order to prevent the costimulatory signals
      required for T cell survival and proliferation. This was achieved by the co
      injection of AV encoding a secreted immunomodulatory molecule (CTLA4-Ig) which
      consists of the extra-cellular domain of mouse CTLA4 fused to the Fc region of
      human IgG. Subretinal co-injection of AV encoding beta galactosidase with AV
      encoding CTLA4-Ig results in prolonged expression in retinal cells compared with
      subretinal injection of only adenovirus encoding beta galactosidase.

PMID- 9930311
TI  - Gene transfer using a disabled herpes virus vector containing the EMCV IRES
      allows multiple gene expression in vitro and in vivo.
AB  - The design of recombinant HSV-1 vectors for delivery of transgenes to the central
      nervous system is undergoing constant development. Problems associated with the
      construction and use of such vectors include the requirement for detection of
      recombinant versus nonrecombinant virus in vitro and also the identification of
      transduced cells in vivo. This could be overcome by the insertion of reporter
      genes such as lacZ or green fluorescent protein (GFP) under a separate promoter
      to the transgene to be expressed. In this case, however, reporter gene expression
      does not necessarily confirm transgene expression as a separate RNA must be
      produced. This study reports the use of an encephalomyocarditis virus internal
      ribosome entry site (IRES) to enable the translation of two reporter genes from a
      single mRNA transcript driven by the same promoter within a disabled HSV vector,
      and discusses the potential advantages of this approach.

PMID- 9930312
TI  - Provision of positive and negative selections in retroviral vectors containing
      the cytosine deaminase gene.
AB  - The E. coli cytosine deaminase (CD) provides a negative selection system for
      suicide gene therapy as CD transfectants are eliminated following 5
      fluorocytosine (5FC) treatment. Here we report a positive selection system for
      the CD gene using 5-fluorouracil (5FU) and cytosine in selection medium to screen
      for CD-positive transfectants. It is based on the relief of 5FU toxicity by
      uracil which is converted from cytosine via CD catalysis, as uracil competes with
      the toxic 5FU in subsequent pyrimidine metabolism. Hence, a retroviral vector
      containing the CD gene may provide both positive and negative selections after
      gene transfer. The CD transfectants selected with the positive selection system
      showed susceptibility to 5FC in subsequent negative selection in vitro and in
      vivo. Therefore, this dual selection system is useful not only for combination
      therapy with transgene and CD gene, but can also act to eliminate selectively
      transduced cells after the transgene has furnished its effects or upon undesired
      conditions if 5FC is applied for negative selection in vivo.

PMID- 9930313
TI  - FMEV vectors: both retroviral long terminal repeat and leader are important for
      high expression in transduced hematopoietic cells.
AB  - FMEV retroviral vectors combine the long terminal repeat of Friend mink cell
      focus-forming viruses with the 5' untranslated leader region of the murine
      embryonic stem cells virus. These modules were connected to achieve high
      transgene expression in hematopoietic progenitor and stem cells. Here, we report
      the cloning of safety-improved and versatile FMEV vectors allowing module-wise
      exchange of crucial elements for comparative studies. By transfer and expression
      of four different marker genes (neomycin phosphotransferase, lacZ, enhanced green
      fluorescent protein and truncated low affinity nerve growth factor receptor), we
      formally demonstrate that both the long terminal repeat and the leader contribute
      to the high expression of FMEV in transduced hematopoietic cells. Most prominent
      are the data recorded in the absence of selection in myelo-erythroid progenitor
      cells. Here, FMEV vectors mediate up to two orders of magnitude increased
      transgene expression levels when compared with vectors based on the Moloney
      murine leukemia virus.

PMID- 9930314
TI  - Genetic re-targeting of T lymphocyte specificity.

PMID- 9930315
TI  - Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in
      photoreceptor cell death in the rd/rd mouse.
AB  - Gene transfer to retinal cells may provide a means to retard photoreceptor cell
      death and thus prevent blindness in diseases such as retinitis pigmentosa. We
      tested the possibility of interfering with apoptotic photoreceptor cell death in
      the rd mouse through subretinal delivery of a recombinant replication-defective
      adenovirus containing the human cDNA for bcl-2, Ad.2.5HRPbcl-2. Photoreceptor
      specific transgene expression was accomplished through incorporation of the 2.5
      kb human rhodopsin upstream fragment (HRP). Ad.2.5HRPbcl-2 was injected alone or
      in combination with Ad.CMVPDE beta. Ad.CMVPDE beta contains a cDNA encoding the
      beta subunit of cGMP phosphodiesterase (PDE beta). Recombinant viruses containing
      lacZ (driven either by the cytomegalovirus (CMV) promoter/enhancer or HRP) and of
      Ad.CMVPDE beta and vehicle alone were injected in contralateral eyes as control.
      Injection of Ad.2.5HRPbcl-2 in the rd mouse resulted in histologically detectable
      rescue lasting 6 weeks after birth. Extent of rescue was not as large as after
      delivery of wildtype PDE beta, the gene defective in the rd mouse. However,
      delivery of genes which prevent apoptotic cell death may have broad application
      to gene therapy of retinal degenerative diseases.

PMID- 9930316
TI  - Early biological effect of in vivo gene transfer of platelet-derived growth
      factor (PDGF)-B into healing patellar ligament.
AB  - To define the early biological effect of in vivo introduction of the PDGF-B gene
      on the healing of ligaments, a HVJ-liposome suspension containing platelet
      derived growth factor (PDGF)-B cDNA was injected directly into the injured
      patellar ligament of 14-week-old male Wistar rats. Rats were killed at 1, 4 and 8
      weeks for the morphological analysis of angiogenesis by laminin
      immunohistochemistry and of collagen deposition by Masson's Trichrome staining
      and collagen I immunohistochemistry. PDGF-B gene transfer caused the enhanced
      expression of PDGF in healing ligament up to 4 weeks after transfection, leading
      to an initial promotion of angiogenesis and subsequent enhanced collagen
      deposition in the wound. Enhanced and accelerated matrix synthesis in the PDGF-B
      gene introduced healing ligament suggests that this gene transfer technique may
      be a potentially useful tool for improving soft tissue repair.

PMID- 9930317
TI  - Phenotypic knock-out of the latent membrane protein 1 of Epstein-Barr virus by an
      intracellular single-chain antibody.
AB  - Epstein-Barr virus (EBV) causes lymphoproliferative diseases in immunocompromised
      patients and is associated with endemic Burkitt lymphoma, nasopharyngeal
      carcinoma and some cases of Hodgkin disease. The latent membrane protein 1 (LMP1)
      of EBV is a transmembrane protein that is essential for the transformation of B
      lymphocytes. LMP1-mediated up-regulation of Bcl-2 is thought to be an important
      element in this process. As an approach to explore novel treatments for EBV
      associated lymphomas, we constructed a single-chain antibody (sFv) directed
      against LMP1 to achieve functional inhibition of this oncoprotein in EBV
      transformed B lymphocytes. We demonstrated that intracellular expression of an
      endoplasmic reticulum (ER)-targeted form of this sFv markedly reduced LMP1
      protein levels. We also observed a decrease in intracellular level of this
      protein which correlated with a marked reduction of Bcl-2 expression in EBV
      transformed B lymphocytes. We further demonstrated that anti-LMP1 sFv-mediated
      reduction of Bcl-2 correlated with increased sensitivity of these cells to drug
      induced cell death. Therefore, these data suggest that an anti-LMP1 sFv used in
      combination with conventional chemotherapy may be useful for gene therapy of EBV
      associated lymphomas in immunocompromised patients.

PMID- 9930318
TI  - Enhanced in vitro and in vivo gene delivery using cationic agent complexed
      retrovirus vectors.
AB  - Retroviruses are, at present, the most efficient integrative vectors available
      for gene delivery. However, these viruses are still limited by relatively low
      titres. Although several protocols exist to improve virus titre most of them are
      time-consuming and unable to provide sufficient virus for in vivo applications.
      Virus titre can be enhanced by polybrene and other cationic agents. By
      investigating a broad range of cationic agents for their ability to enhance virus
      infectivity we found that both ecotropic and amphotropic retrovirus infection
      could be increased. In particular, the lipopolyamine
      dioctadecylamidoglycylspermine (DOGS) gave up to one order of magnitude
      enhancement above polybrene-mediated infection without cytotoxicity. To increase
      virus infectivity further we combined the enhancing effect of DOGS on virus
      infectivity with concentration of virus particles by ultrafiltration to reach
      titres of 1 x 10(9) IU/ml. The in vivo transduction of regenerating rat liver, by
      an amphotropic retrovirus was increased approximately five-fold by the addition
      of DOGS compared with virus alone. There was no animal toxicity observed
      following the administration of DOGS. The improved transduction efficiency seen
      both in vitro and in vivo following the co-administration of DOGS/virus complexes
      may be useful for future gene therapy applications.

PMID- 9930319
TI  - Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates
      experimental malignant glioma growth in vivo.
AB  - Cytokines such as transforming growth factor-beta (TGF-beta) are thought to
      mediate escape from immune surveillance in human malignant glioma. Here, we
      report that ectopic expression of the small TGF-beta-binding proteoglycan,
      decorin, inhibits not only TGF-beta bioactivity but also TGF-beta 1 and TGF-beta
      2 mRNA transcription and TGF-beta protein synthesis by human LN-18, LN-229, T98G
      and rat C6 glioma cells in vitro. Ectopic expression of decorin in C6 rat glioma
      cells results in strong inhibition of tumor formation in vivo. Decorin-expressing
      C6 gliomas grow initially but regress to very small residual tumors at 12 weeks
      after implantation whereas all control animals die or have to be killed within 4
      weeks. Decorin-expressing tumors show a four-fold increase of infiltration by
      activated T cells and a 1.6-fold increase in total B and T cells. Chronic steroid
      mediated immunosuppression abrogates the inhibitory effects of decorin gene
      transfer. We conclude that decorin-induced inhibition of TGF-beta release by
      glioma cells significantly enhances antiglioma immune responses in vivo. Clinical
      evaluation of decorin gene therapy for human malignant gliomas may be warranted.

PMID- 9930320
TI  - A retroviral vector system 'STITCH' in combination with an optimized single chain
      antibody chimeric receptor gene structure allows efficient gene transduction and
      expression in human T lymphocytes.
AB  - Genetic engineering of T lymphocytes for adoptive clinical immunotherapy calls
      for efficient gene transduction methods. Therefore, a transient retroviral gene
      transduction system 'STITCH' was developed comprising pSTITCH retroviral vector
      encoding the transgene, plasmids encoding Moloney murine leukemia virus gag/pol
      and gibbon ape leukemia virus envelope, and the human kidney cell line 293T as a
      packaging line. Cotransfection of retroviral vector and packaging plasmids in
      293T cells results in the production of GALV env pseudotyped viral particles with
      a titer of 10(7) infectious units per milliliter. The 'STITCH' gene transduction
      system efficiently transduces genes into activated human T lymphocytes derived
      from healthy donors and cancer patients. The efficacy of gene transduction is
      donor-independent. A direct application of the 'STITCH' gene transduction system
      is the genetic engineering of activated human T lymphocytes to induce expression
      of antibody based chimeric receptors in their membrane. Introduction of these
      chimeric receptors into activated human T lymphocytes graft these cells with
      specificity for, for example, renal cell carcinoma. In order to study the effect
      of the chimeric receptor gene structure on the processes ultimately leading to
      functional membrane expression, we designed a number of different chimeric
      receptor gene structures and subsequently compared their membrane expression on
      293T cells and activated human T lymphocytes. Distinct membrane expression
      densities were observed on 293T cells and human T lymphocytes for the different
      chimeric receptor gene constructs. Gene transduction of activated human T
      lymphocytes with four out of five chimeric receptor gene constructs resulted in
      functional expression of chimeric receptor as demonstrated by specific
      recognition and cytolysis of renal cell carcinoma.

PMID- 9930321
TI  - Mutual exclusivity of DNA binding and nuclear localization signal recognition by
      the yeast transcription factor GAL4: implications for nonviral DNA delivery.
AB  - A novel approach to nonviral DNA delivery is the use of combinations of DNA
      binding proteins such as the yeast transcriptional activator GAL4 and plasmid DNA
      containing the specific binding sequence of the DNA-binding protein inserted
      within it, in addition to the gene of interest to be transferred into target
      cells. The amino terminal 147 amino acids of GAL4 contain a DNA-binding domain
      that has been shown to bind specifically to a 17 bp nucleotide recognition
      sequence, while the amino terminal 74 amino acids have been shown to be
      sufficient to target large heterologous proteins to the nucleus. Although it has
      been previously exploited as a gene transfer vehicle, the exact relationship
      between GAL4's DNA binding and nuclear targeting activities has not been
      investigated. Using gel mobility shift assays and ELISA-based binding assays,
      this study examines this issue directly, establishing the mutual exclusivity of
      the DNA-binding and nuclear targeting activities of GAL4. We demonstrate that
      GAL4(1-147) can specifically enhance transfection of plasmids containing the 17
      bp recognition sequence. Interestingly, we found that the nuclear localization
      signal (NLS) of GAL4 is distinct from conventional NLSs, such as those of the
      SV40 large tumor antigen and bipartite NLSs, in that it is recognized exclusively
      by the nuclear pore targeting beta-subunit of the NLS-receptor importin complex,
      rather than the alpha-subunit. Specific binding to DNA was blocked by beta
      subunit binding, while the converse was also true, making the GAL4-NLS novel in
      being regulated by DNA binding; this may play an important role in effecting
      release of GAL4 from the beta-subunit following transport through the nuclear
      pore. This study encompasses the first direct analysis of NLS
      recognition/accessibility in vehicles for nonviral DNA transfer, with the results
      having relevance to the use of GAL4 and comparable DNA-binding proteins in such
      vehicles.

PMID- 9930322
TI  - Highly controlled gene expression using combinations of a tissue-specific
      promoter, recombinant adenovirus and a tetracycline-regulatable transcription
      factor.
AB  - Controllable gene expression is a desirable feature both in gene therapy
      protocols and for the study of gene function in animals and plants. We have
      exploited the modular character of the tetracycline (tc)-regulatable genetic
      switch to show that its components can be encoded by any combination of
      recombinant adenovirus and/or transgenic mice. Transgenic mice were constructed
      that express the tc-regulatable trans-activator tTA muscle specifically. These
      were injected with recombinant adenovirus expressing a luciferase reporter
      controlled by the tTA-regulatable promoter. Virus injected into muscle, but not
      into a control organ (brain) resulted in luciferase activity. Conversely,
      injection of tTA producing adenovirus into mice that were transgenic for a
      trkB/Fc fusion protein gene under tc promoter control resulted in swift
      expression of serum trkB/Fc receptor-body. Both modes of gene induction were
      fully inhibited by administration of tc. We demonstrate that a careful choice of
      these tools allows exquisite in vivo control over transgene expression in a
      temporal, tc-regulatable, topical and tissue-specific manner.

PMID- 9930323
TI  - In vitro and in vivo effects of retrovirus-mediated transfer of the connexin 43
      gene in malignant gliomas: consequences for HSVtk/GCV anticancer gene therapy.
AB  - In tumors, gap junctional intercellular communication (GJIC) is usually down
      regulated and the expression of connexins, membrane proteins constituting gap
      junction channels, is often low or altered. GJIC, allowing the intercellular
      diffusion of ganciclovir (GCV) triphosphate, is also one mediator of the
      'bystander effect', the phenomenon by which herpes simplex virus thymidine kinase
      (HSVtk)-transduced, neoplastic cells kill surrounding HSVtk-negative cells when
      treated with GCV. We set up experiments to evaluate the effects of retrovirus
      mediated in vivo gene transfer of connexin 43 in malignancies with low GJIC
      capacity. We found that U-87 human glioblastoma cells transfected in vitro by the
      human Cx43 cDNA grow significantly more slowly than control U-87 cells and lose
      their tumorigenicity when injected subcutaneously in nude mice. When the Cx43
      gene was transduced in vitro in U-87 cells by a retroviral producer cell line
      (N3.2.ii, titer 1.5 x 10(6) c.f.u./ml) in vivo results were similar. However,
      only when U-87 cells were co-injected with N3.2.ii cells in nude mice in a 1:5
      ratio, a 50% reduction in tumor size was obtained during the first 3 weeks.
      Moreover the coinjection of U-87 cells with N3.2.ii and SBA cells (a retroviral
      producer cell line expressing the HSVtk gene), was not able to potentiate the
      effects of GCV administration, suggesting that Cx43 gene transfer requires more
      efficient vectors to increase the bystander effect in vivo.

PMID- 9930324
TI  - Effective reversal of a transformed phenotype by retrovirus-mediated transfer of
      a ribozyme directed against mutant N-ras.
AB  - A hammerhead ribozyme directed against oncogenic N-ras (N13-ras) was introduced
      into a retroviral vector and its activity evaluated in vitro and in cell lines.
      The catalytic efficiency of the ribozyme embedded within a 2618 nucleotides in
      vitro-generated transcript was not significantly affected by the length of non
      base pairing flanking sequences. A sensitive assay based on N-ras/luciferase
      fusion transcripts as a reporter system was used to assess ribozyme activity in
      mammalian cells. More than 95% reduction in luciferase activity was observed in
      cells transduced with a retrovirus containing the active form of the ribozyme,
      whereas no significant reduction was observed with the inactive form of the same
      ribozyme. In order to assay the activity of the retrovirally encoded ribozyme in
      a biological setting, the IL-3-dependent cell line TF-1 was transformed with N13
      ras. Expression of N13-ras in these cells induced factor-independent colony
      growth and a dose-dependent proliferative response to erythropoietin (Epo).
      Retrovirus-mediated expression of the active form of the ribozyme in these cells
      restored factor-dependent colony growth and abolished the proliferative response
      to Epo. The reversion of the transformed phenotype correlated with a reduction in
      the amount of N13-ras mRNA.

PMID- 9930325
TI  - The contribution of poly-L-lysine, epidermal growth factor and streptavidin to
      EGF/PLL/DNA polyplex formation.
AB  - High-level targeted gene delivery has been demonstrated by molecular conjugates
      in vitro; however, in vivo delivery has been limited. The complexity of the
      resulting protein/DNA polyplex and a lack of understanding of its formation are
      persistent limitations. In this report, we show the effect of the DNA-binding
      agent poly-L-lysine (PLL), the ligand epidermal growth factor (EGF), and the
      coupling protein streptavidin on particle size, charge and gene delivery. Smaller
      (< 80 nm) and more stable polyplexes were obtained with PLL1116 than with shorter
      versions of PLL, especially in 0.15 M NaCl. Stability was increased by adding
      streptavidin to the polyplex; however, EGF increased particle size (> 1000 nm)
      and decreased gene delivery when > 300 EGF molecules per polyplex were used,
      indicating that a critical number of EGF molecules was needed for efficient gene
      delivery. The correct combination of these components resulted in the most
      efficient gene delivery in vitro and now provide for testing a more stable
      protein/DNA polyplex to aid in enhancing gene delivery in vivo.

PMID- 9930326
TI  - Enhanced reporter gene expression in cells transfected in the presence of DMI-2,
      an acid nuclease inhibitor.
AB  - Cellular nuclease activity is a potential barrier to the successful delivery of
      foreign genes to mammalian cells. We tested the hypothesis that transfection in
      the presence of a specific DNase inhibitor can enhance the expression of foreign
      gene products. We have used DMI-2, a polyketide metabolite of Streptomyces sp.
      strain 560 to enhance the expression of bacterial chloramphenicol
      acetyltransferase (CAT) in the human lung adenocarcinoma cell line H441. DMI-2
      has been shown previously to inhibit porcine DNase II, an acid pH nuclease
      contained in the endosomal/lysosomal compartment. Transfection of H441 cells in
      the presence of 0.1-1 microgram/ml DMI-2 caused: (1) 10-fold enhancement of CAT
      activity when the bacterial plasmid was complexed with either surfactant protein
      A-poly-lysine or transferrin-poly-lysine; (2) 1.5- to two-fold enhancement of CAT
      activity in cells exposed to lipofectin-DNA complexes: (3) no effect on
      transfection via calcium phosphate co-precipitation. DMI-2 alone showed no
      inherent transfection activity. In experiments using SP-A-poly-lysine and plasmid
      containing the beta-galactosidase reporter gene, DMI-2 increased the number of
      transfected cells. Methanolysis products of DMI-2 did not inhibit DNase II and
      did not enhance transfection efficiency. Taken together, the data support the
      hypothesis that nuclease action is a significant barrier to expression of foreign
      genes and inhibition of specific nucleases may facilitate transfection.

PMID- 9930327
TI  - Construction of new retroviral producer cells from adenoviral and retroviral
      vectors.
AB  - A combination of adenoviral and retroviral vectors was used to construct second
      generation packaging cells that deliver marker genes to target cells. A vector
      based upon Moloney murine leukemia virus (MoMLV) was used to deliver marker
      genes, and an adenovirus-based delivery system was used to deliver MoMLV
      structural genes (gag pol and env) to cultured cells. The procedure transformed
      the cells into new retroviral producer cells, which generate replication
      incompetent retroviral particles in the culture supernatant for transferring
      marker genes to target cells. The titer of the retroviral-containing supernatant
      generated from the second generation producer cells reached above 10(5)
      c.f.u./ml, which is comparable to the MoMLV-based producer cell lines currently
      used in human gene therapy trials. These observations suggest that this new gene
      transfer scheme is technically feasible. The vector and procedures may be adapted
      for experimental human gene therapy in which the new producer cells are
      transplanted into patients for continuous gene transfer.

PMID- 9930328
TI  - An interaction between penton base and alpha v integrins plays a minimal role in
      adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo.
AB  - Studies in cultured cell lines have shown that adenovirus infection involves
      binding of adenovirus fiber to its cell surface receptor and binding of penton
      base to alpha v integrins. However, much less is known about the role of these
      interactions in cells that are targets for adenovirus-mediated gene transfer.
      Earlier work showed that hepatocytes are readily infected by adenovirus, making
      them an attractive target for gene therapy in several diseases. We found that
      addition of fiber protein blocked adenovirus infection of primary cultures of
      hepatocytes. This suggests an important role for fiber and its receptor. However,
      mutation of the integrin-binding motif in penton base did not inhibit infection
      of hepatocytes, even though the mutation impaired infection of HeLa cells.
      Hepatocytes had undetectable amounts of alpha v integrins on their cell surface
      and showed no specific adherence to vitronectin, the natural substrate of alpha v
      integrins. Adenovirus with an intact penton base enhanced infection of liver
      following intravenous injection, but only by three-fold as compared with virus in
      which the integrin-binding motif was disrupted. These studies suggest that
      interactions between cell surface integrins and penton base are not required for
      adenovirus infection of hepatocytes in vitro, but the interaction enhances
      infection to a small degree in vivo.

PMID- 9930329
TI  - Abrogation of TGF-beta activity during retroviral transduction improves murine
      hematopoietic progenitor and repopulating cell gene transfer efficiency.
AB  - Transforming growth factor-beta has complex activities on hematopoietic cells. We
      have previously shown that murine long-term repopulating activity is compromised
      by ex vivo culture in TGF-beta 1 and conversely is increased by abrogating
      endogenous TGF-beta activity with a neutralizing antibody. In the current study,
      we investigated the effect of abrogation of autocrine or paracrine TGF-beta
      present during retroviral transduction on gene transfer efficiency to primitive
      hematopoietic cells. Murine marrow cells were cultured and retrovirally
      transduced for 4 days in the presence of interleukin-3, interleukin-6 and stem
      cell factor, and either a neutralizing anti-TGF-beta antibody or an isotype
      control. Committed progenitor cells were analyzed for gene transfer efficiency,
      and cells were also injected into W/Wv recipient mice for analysis of
      transduction of long-term repopulating cells. The progenitor (CFU-C) transduction
      efficiency in the presence of anti-TGF-beta was significantly greater.
      Semiquantitative PCR analysis and Southern blot analysis for the retroviral
      marker gene in the blood and bone marrow of recipient mice revealed a significant
      increase in the transduction efficiency of long-term repopulating cells after
      culture and transduction in the presence of the anti-TGF-beta. Thus
      neutralization of TGF-beta activity during retroviral transduction allows more
      efficient gene transfer into primitive murine hematopoietic cells and may prove
      beneficial in future clinical gene transfer or therapy trials.

PMID- 9930330
TI  - Stable and monodisperse lipoplex formulations for gene delivery.
AB  - A stable single vial lipoplex formulation has been developed that can be stored
      frozen without losing either biological activity or physical stability. This
      formulation was identified by systematically controlling several formulation
      variables and without introducing either stabilizers or surfactants. Analytical
      assays were used to unambiguously characterize the formulations. The critical
      formulation parameters were: (1) the size of the cationic liposomes; (2) the rate
      and method of DNA and cationic liposome mixing; and (3) the ionic strength of the
      suspending vehicle. The mixing conditions were precisely controlled by using a
      novel, specially designed continuous flow pumping system in which the DNA and
      liposome solutions were mixed at the junction of a T-connector. Homogenous
      cationic liposome preparations were prepared by extrusion in two different size
      ranges of either 400 or 100 nm. Extruded liposomes produced more monodisperse and
      physically stable lipoplex formulations than unextruded liposomes, but the
      formulations prepared with 100 nm liposomes were less active in in vitro
      transfection assays than either the 400 nm or unextruded liposomes. Low ionic
      strength and 5% sorbitol were required for the lipoplex formulations to survive
      freezing and thawing. A frozen lipoplex formulation stored for more than a year
      maintained its biological activity. These results have broad implications for the
      pharmaceutical development of lipoplex formulations for gene delivery.

PMID- 9930331
TI  - Inflammatory responses following direct injection of plasmid DNA into skeletal
      muscle.
AB  - Transfer of genes by injection of plasmid DNA into skeletal muscle has a wide
      variety of applications ranging from treatment of neuromuscular disorders to
      genetic vaccination. We examined each component involved in the intramuscular
      injection of plasmid DNA in terms of the induction of inflammatory responses. The
      insertion of a needle and the injection of a relatively large volume of saline
      caused very little muscle damage except in rare cases. In contrast, barium
      chloride-induced regeneration of muscle, injection of lipopolysaccharide, plasmid
      backbone or plasmid expressing a neo-antigen (beta-galactosidase) all generated
      widespread inflammation of injected muscle, with mononuclear infiltrate,
      comprised largely of macrophages and with both CD4+ and CD8+ T lymphocytes,
      present. Such inflammation may hamper clinical application of this technology and
      may encourage undesirable immune responses in gene therapy trials. Inflammation
      was not greatly reduced by CD4- or CD8-depleting antibodies, suggesting this
      initial inflammation did not involve T cells, but methylation of plasmid DNA
      before injection substantially lessened the inflammatory response and resulted in
      longer term expression of the transgene.

PMID- 9930332
TI  - Polyethylenimine-based intravenous delivery of transgenes to mouse lung.
AB  - Generally, cationic vector-based intravenous delivery of DNA is hindered by
      interactions of positively charged complexes with serum proteins. However, if
      optimally formulated, cationic vectors can provide reasonable levels of
      transfection in the lung either by intravenous or intrapulmonary routes. We
      investigated the in vivo transfection capacity of a cationic polymer: linear, 22
      kDa polyethylenimine. PEI/DNA complexes were formulated in 5% glucose and
      delivered into adult mice through the tail vein. Two marker genes were used, beta
      galactosidase and luciferase. High levels of luciferase expression (10(7) RLU/mg
      protein) were found in the lung when DNA was complexed with PEI at a ratio of 4
      nitrogen equivalents per DNA phosphate. Lower levels of transfection were found
      in the heart, spleen, liver and kidney. Expression was dose- and time-dependent
      in all tissues examined. In the lung, beta-galactosidase staining showed
      transgene expression in clusters of 10 or more pulmonary cells including the
      alveolar endothelium, squamous and great alveolar epithelial cells (type I and II
      pneumocytes) and septal cells. These findings indicate that the complexes pass
      the capillary barrier in the lung. Although the delivery mechanism requires
      elucidation, linear PEI has promise as a vector for intravenous transfer of
      therapeutic genes.

PMID- 9930333
TI  - The proteasome system: a neglected tool for improvement of novel therapeutic
      strategies?

PMID- 9930334
TI  - Expression of a retrovirally transduced gene under control of an internal
      housekeeping gene promoter does not persist due to methylation and is restored
      partially by 5-azacytidine treatment.
AB  - Although expression of transgenes under the control of a retroviral long terminal
      repeat (LTR) promoter has been shown not to persist due to methylation, it has
      been observed that internal promoter may be active even if expression from the
      LTR promoter is silent. We constructed a retroviral vector carrying the herpes
      simplex virus thymidine kinase (HSVtk) gene under the control of the albumin gene
      promoter and transduced the HSVtk gene into hepatocellular carcinoma cells. Three
      of 14 mice, however, could not eradicate HSVtk-transduced grafts completely
      despite ganciclovir (GCV) treatment. These GCV-refractory cell lines exhibited
      resistance to GCV after recultivation. Subsequent Southern blot analysis revealed
      that the HSVtk gene was not deleted but extensively or completely methylated in
      GCV-refractory lines. Treatment with 5-azacytidine, a demethylating agent,
      partially restored the sensitivity of GCV-refractory lines to GCV. These results
      indicate that expression of retrovirally transduced gene may not persist in vivo
      due to methylation even when the gene is directed by an internal housekeeping
      gene promoter. These observations may also have important implications for future
      clinical applications of retrovirus-mediated gene therapy.

PMID- 9930335
TI  - Transfection of cultured myoblasts in high serum concentration with DODAC:DOPE
      liposomes.
AB  - The inhibitory effect of serum is one of the main obstacles to the in vivo use of
      cationic liposomes as a DNA delivery system. We have found that a novel liposome
      formulation, DODAC:DOPE (1:1) is totally resistant to the inhibitory effects of
      serum for transfection of cultured myoblasts and myotubes. Transfection with a
      lacZ reporter gene in the presence of 95% fetal bovine serum gave up to 25% beta
      gal-positive cells in C2C12 myoblasts and about six-fold less in primary human
      myoblasts. The lower transgene expression in primary cells does not appear to be
      a result of less DNA uptake but might result from differences in intracellular
      trafficking of the complexes. DODAC-based liposomes are unique in their
      resistance to serum inhibition and may therefore be valuable for the systemic
      delivery of genetic information to muscle and other tissues.

PMID- 9930336
TI  - Adenovirus-mediated gene transfer results in decreased lysosomal storage in brain
      and total correction in liver of aspartylglucosaminuria (AGU) mouse.
AB  - Aspartylglucosaminuria (AGU) is a lysosomal storage disease leading to mental
      retardation, which is caused by deficiency of aspartylglucosaminidase (AGA). AGU
      is strongly enriched in the Finnish population in which one major mutation called
      AGU(Fin) has been identified. The molecular pathogenesis of AGU as well as the
      biology of the AGA enzyme have been extensively studied, thus giving a profound
      basis for therapeutic interventions. In this study we have performed adenovirus
      mediated gene transfer to the recently produced mouse model of AGU, which
      exhibits similar pathophysiology as that in humans. Recombinant adenovirus
      vectors encoding for the human AGA and AGU(Fin) polypeptides were first applied
      in primary neurons of AGU mouse to demonstrate wild-type and mutant AGA
      expression in vitro. In vivo, both of the adenovirus vectors were injected into
      the tail vein of AGU mice and the expression of AGA was demonstrated in the
      liver. The adenovirus vectors were also injected intraventricularly into the
      brain of AGU mice resulting in AGA expression in the ependymal cells lining the
      ventricles and further, diffusion of AGA into the neighbouring neurons. Also, AGA
      enzyme injected intraventricularly was shown to transfer across the ependymal
      cell layer. One month after administration of the wild-type Ad-AGA, a total
      correction of lysosomal storage in the liver and a partial correction in brain
      tissue surrounding the ventricles was observed. After administration of the Ad
      AGU virus the lysosomal storage vacuoles in liver or brain remained unchanged.
      These data demonstrate that the lysosomal storage in AGU can be biologically
      corrected and furthermore, in the brain a limited number of transduced cells can
      distribute AGA enzyme to the surrounding areas.

PMID- 9930337
TI  - Corrective gene transfer of keratinocytes from patients with junctional
      epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed
      epithelia.
AB  - Herlitz junctional epidermolysis bullosa (H-JEB) provides a promising model for
      somatic gene therapy of heritable mechano-bullous disorders. This genodermatosis
      is caused by the lack of laminin-5 that results in absence of hemidesmosomes (HD)
      and defective adhesion of squamous epithelia. To establish whether re-expression
      of laminin-5 can restore assembly of the dermal-epidermal attachment structures
      lacking in the H-JEB skin, we corrected the genetic mutation hindering expression
      of the beta 3 chain of laminin-5 in human H-JEB keratinocytes by transfer of a
      laminin beta 3 transgene. The transduced keratinocytes synthesized a recombinant
      beta 3 polypeptide that assembled with the endogenous laminin alpha 3 and gamma 2
      chains into a biologically active laminin-5 that was secreted, processed and
      deposited into the extracellular matrix. Re-expression of laminin-5 induced cell
      spreading, nucleation of hemidesmosomal-like structures and enhanced adhesion to
      the culture substrate. Organotypic cultures performed with the transduced
      keratinocytes, reconstituted epidermis closely adhering to the mesenchyme and
      presenting mature hemidesmosomes, bridging the cytoplasmic intermediate filaments
      of the basal cells to the anchoring filaments of the basement membrane. Our
      results provide the first evidence of phenotypic reversion of JEB keratinocytes
      by somatic gene therapy and demonstrate that genetic treatment of the mild forms
      of skin blistering diseases and other inherited extracellular matrix pathologies
      is a realistic goal.

PMID- 9930338
TI  - The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in
      vivo.
AB  - Gene transfer in the lung holds promise for the treatment of diseases such as
      pulmonary fibrosis, cystic fibrosis and asthma. Pulmonary surfactant has been
      reported to enhance expression from endobronchial, adenovirus-mediated gene
      transfer in experimental animals. This study examines the effect of exogenous
      synthetic surfactant (Exosurf) on gene expression from naked plasmid DNA
      administered endobronchially to adult mice. Transfection efficiency was evaluated
      by quantifying the expression of chloramphenicol acetyltransferase (CAT) and
      luciferase (Luc) genes in the lung. Endobronchial administration of either CAT or
      Luc expression plasmid DNA resulted in detectable concentrations of each reporter
      protein. CAT expression from plasmid DNA was monitored after endobronchial
      administration with the maximal expression observed at 3-5 days after
      administration and decreasing for 5 days thereafter. When DNA was delivered in a
      50% suspension of Exosurf, the expression of either CAT or Luc was significantly
      reduced by 89.6 +/- 1.4% and 82.7 +/- 10.5%, respectively. The decrease in Luc
      expression was closely correlated (r = 0.99, P < 0.001) to log concentration of
      surfactant in the plasmid buffer solution (IC50 = 8.6%). CAT expression was not
      altered when surfactant was administered either 2 h before or after plasmid DNA
      instillation. Examination of the components of Exosurf revealed that two
      compounds, DPPC and tyloxapol, showed inhibitory effects on CAT expression.
      However, the inhibition caused by Exosurf appeared greater than that of either
      component. Our results suggest that the lung surfactant is a barrier to
      transfection of the endobronchial airway and may be partly responsible for the
      low expression of exogenous DNA in vivo in the bronchial tree.

PMID- 9930339
TI  - Expression of human dystrophin following the transplantation of genetically
      modified mdx myoblasts.
AB  - Transplantation of genetically modified autologous myoblasts has been proposed as
      a possible solution to avoid long-term use of immunosuppressive drugs. To
      determine the conditions to be used in this kind of approach for possible
      treatment of dystrophin deficiency, mdx myoblasts were infected at different
      multiplicities of infection (MOI or 0.01-1000) with an adenoviral vector
      containing a CMV promoter/enhancer driven 6.3 kb human dystrophin cDNA (minigene)
      and tested in vitro for transgene expression. In these cultures, dystrophin mRNA
      was found to be proportionate with increasing MOI. Primary myoblast cultures
      derived from transgenic mdx mice expressing beta-Gal under a muscle-specific
      promoter and showing high expression of the human mini-dystrophin transgene
      introduced by the adenoviral vector were grafted into anterior tibialis muscles
      of SCID mice. Ten and 24 days after transplantation, numerous muscle fibers
      expressing both human dystrophin and beta-Gal were detected throughout the mouse
      muscles by immunohistochemistry using an antibody specific for human dystrophin.
      The presence of the human mini-dystrophin mRNA was also detected by RT-PCR. These
      results demonstrate that three essential conditions in autologous myoblast
      transplantation can be achieved: (1) in vivo survival of at least some of the
      transduced myoblasts; (2) efficient fusion of these cells with the host muscle
      fibers; and (3) the high expression of the dystrophin transgene in situ.
      Furthermore, this article provides a novel RT-PCR-based technique to quantify the
      human dystrophin minigene expression in vitro and in vivo.

PMID- 9930340
TI  - Targeted gene transfer to corneal endothelium in vivo by electric pulse.
AB  - A novel method of in vivo targeted gene transfer to intentionally selected areas
      of the corneal endothelium was developed. Plasmid DNA with the lacZ gene coding
      for beta-galactosidase was injected into the anterior chamber of adult Wistar
      rats, and eight pulses of electricity at intensities ranging from 5 to 40 V/cm
      were delivered for 50 ms to the cornea with a specially designed electric probe
      in order to determine the effect of gene transfer on the corneal endothelial
      cells. Gene expression was visualized by enzymatic color reaction using X-gal in
      enucleated eyes on days 1, 3, 7, 14 and 21 after gene transfer. The treated eyes
      were then photographed and the X-gal-positive areas were evaluated by an image
      analyzer. The ratios of the areas (X-gal-positive area/area of entire corneal
      endothelium x 100%) were then calculated to determine gene transfection
      efficiency. The expression of beta-galactosidase was clearly detected in the
      cytoplasm of the corneal endothelial cells as early as day 1 and lasted until day
      21. The most intense gene expression was observed on days 1 and 3 (5.21% on day 1
      and 6.45% on day 3). The expression of beta-galactosidase on day 3 was most
      evident following delivery of 20 V electric pulses (0.09% at 5 V, 0.03% at 10 V,
      6.45% at 20 V). beta-Galactosidase expression was limited to the corneal
      endothelial cells in highly selected areas and no beta-galactosidase expression
      was detected in any other intra- or axtraocular tissues. In addition, no cell
      damage was apparent in the cornea and no inflammation was detected in any other
      intraocular tissues. Thus, low-voltage electric pulses successfully transferred
      the gene of interest to highly selective areas of the corneal endothelium without
      inducing any pathological changes. This targeted gene transfer method appears to
      have great potential for use in gene therapy for ocular diseases.

PMID- 9930342
TI  - Tumor cell-specific transgene expression prevents liver toxicity of the adeno
      HSVtk/GCV approach.
AB  - Treatment of colorectal liver metastases with the HSVtk/GCV approach and
      adenoviral vectors is highly toxic. We present a nontoxic alternative using the
      cell type-specific CEA promoter instead of the widely used hCMV immediate-early
      promoter to drive tk gene expression in the context of a recombinant adenovirus.
      Analysis of CEA promoter-dependent tk gene expression showed significant activity
      of this promoter in several human and rat tumor-derived cell lines but not in rat
      primary hepatocytes and in mouse liver, whereas the CMV promoter was highly
      active in all cell types and tissues investigated. CEA promoter-dependent tk gene
      expression was sufficient to kill 100% of cancer cells in vitro, even if less
      than 10% were infected by the adenoviral vector, indicating a significant
      bystander effect. Moreover, treatment of subcutaneous tumors in SCID mice with
      Ad.CEA-tk led to a several-fold reduction of tumor growth, and tail vein
      injection of a high dose of Ad.CEA-tk caused no side-effects in the liver. The
      CMV promoter was more potent than the CEA promoter in mediating GCV sensitivity
      to cancer cells in vitro and in vivo, but even a 20-fold reduction of the dose of
      Ad.CMV-tk did not prevent its liver cell toxicity after systemic application to
      mice and still resulted in the death of all animals within 4 days after the start
      of GCV treatment. These results indicate that restriction of tk gene expression
      to tumor cells in the liver prevents systemic toxicity. Moreover, the CEA
      promoter is a safe and efficient tool for tumor cell-specific expression of
      suicide genes in the liver.

PMID- 9930341
TI  - Vaccine effect of granulocyte-macrophage colony-stimulating factor or CD80 gene
      transduced murine hematopoietic tumor cells and their cooperative enhancement of
      antitumor immunity.
AB  - To develop immunogene therapy targeting minimal residual hematopoietic tumor
      cells in patients, we transduced murine GM-CSF or CD80 gene into murine WEHI 3B
      myelomonocytic leukemia and EL-4 thymic lymphoma cells using retroviral vectors
      and evaluated their effects on inducing antitumor responses in syngeneic host
      mice. Subcutaneously injected GM-CSF- and CD80 gene-transduced WEHI 3B
      (GMCSF/WEHI/3.2 or CD80/WEHI/1.8, respectively) cells lost their original
      tumorigenicity in immunocompetent syngeneic mice. Results from tumor inoculation
      experiments using athymic nude mice suggested that the rejection of
      GMCSF/WEHI/3.2 in immunocompetent mice depended fully on T cells and that of
      CD80/WEHI 1.8 depended partly on T cells and partly on NK cells. In both WEHI 3B
      and EL-4 models, irradiated GM-CSF gene-transduced cells provided strong immuno
      protection against wild-type cells, but irradiated CD80 gene-transduced cells did
      not. A remarkably high cooperative effect was obtained when irradiated GMCSF/EL-4
      and CD80/EL-4 were inoculated together. These results suggested that the tumor
      vaccine effect is efficiently enhanced by GM-CSF gene transduction and CD80 gene
      transduction induces some protective antitumor immunity in co-operation with GM
      CSF gene transduction.

PMID- 9930343
TI  - Long-term connexin-mediated bystander effect in highly tumorigenic human cells in
      vivo in herpes simplex virus thymidine kinase/ganciclovir gene therapy.
AB  - Gene therapy via the herpes simplex virus thymidine kinase (tk) gene and
      ganciclovir (GCV) treatment eliminates experimental tumors. In this approach,
      cells expressing the tk gene (tk+) and neighboring tumor cells which do not
      express the gene are killed. We have demonstrated this bystander effect is
      enhanced in vitro by gap junctional intercellular communication (GJIC). In order
      to extend our in vitro results into in vivo situations, we injected into nude
      mice different ratios of tk+/tk- HeLa cells, either lacking or transfected with
      connexin43 (Cx43), a gene coding for a gap junction protein. When GCV was
      administered before tumors were palpable, fewer animals developed tumors, even
      after a longer period, if the injected cells were mixtures of Cx43(+)-tk+ and
      Cx43(+)-tk- while tumor growth was not prevented with mixtures of HeLa cells not
      expressing Cx43, i.e. Cx43(+)-tk+/Cx43(-)-tk-. When GCV was given after the
      appearance of tumors, the size of the tumors from Cx43- cells was 30% reduced for
      3 weeks if 50% of the injected cells were tk+. However, for cells expressing
      Cx43, the tumor size was 66% reduced if 10% of the cells were tk+. Such a
      reduction demonstrates a long-term bystander effect which is dependent on Cx43
      expression.

PMID- 9930345
TI  - An enhanced EBNA1 variant with reduced IR3 domain for long-term episomal
      maintenance and transgene expression of oriP-based plasmids in human cells.
AB  - The latent replication of oriP-based plasmids in human cells depends on the viral
      oriP-binding transactivator EBNA1. In this report, the effect of the internal
      repeat 3 (IR3 or GlyAla repeat) domain of EBNA1 on long-term maintenance and
      transgene expression of OriP-based plasmids was examined in dividing human cells.
      To assess the potential contribution of different isoforms of EBNA1 specifically,
      the long-term stability of oriP-based plasmids was determined after stable
      transfection of various CMV-driven EBNA1 genes in EBV-negative human B cells.
      Episome copy number was quantified using a novel sensitive assay based on human
      mitochondrial DNA as an internal extrachromosomal control. Using this assay, the
      standard B95.8-derived EBNA1 was compared with its truncated IR3-deleted, form,
      as well as a new EBNA1 isoform cloned from Raji. The results of a 6-month study
      indicate that the isoforms of EBNA1 differ with respect to their efficiency of
      plasmid maintenance. While the EBNA-1 Raji encoding plasmid was the most stable,
      the oriP-based vector expressing the truncated EBNA1 (IR3del) gene was lost at a
      much higher rate than those transducing full size EBNA1s. In parallel, long-term
      reporter gene expression in various human B cell lines was shown to persist at
      the highest level with the oriP-based Raji EBNA-1 construct. These results show
      that the GlyAla domain can positively influence long-term plasmid stability and
      episomal transgene expression.

PMID- 9930344
TI  - Methotrexate selectable retroviral vectors for Gaucher disease.
AB  - To develop a gene therapy protocol suitable for the treatment of a benign disease
      such as Gaucher disease, we have developed two bicistronic vectors that allow
      transduced cells to be selected for with methotrexate (MTX). The two vectors
      differ in the presence or absence of a mutant polyoma enhancer (delta Mo +
      PyF101) replacing the wild-type retroviral enhancer in the LTR. Infection of
      human TF-1 and K562 cells, Gaucher type II fibroblasts and murine hemopoietic
      bone marrow cells conferred MTX resistance and glucocerebrosidase (GC)
      expression. Upon increasing MTX concentrations, the number of proviral copies and
      GC activity increased, demonstrating in vitro selection of retrovirus-transduced
      cells. At high MTX selection pressure, up to 140 microM for infected Gaucher type
      II fibroblasts, no endogenous wild-type DHFR amplification could be detected,
      indicating that both retroviral constructs provide sufficient DHFR protein
      levels. Upon transduction, murine bone marrow cells were protected against
      otherwise lethal MTX concentrations (range 1-5 microM MTX). Flow cytometry
      specific for human GC (hGC) demonstrated that in vitro selection resulted in
      increased percentages of hGC-positive murine cells. In conclusion, the generated
      bicistronic vectors are ideally suited to investigate whether an in vivo
      selection approach for retrovirus-transduced cells is feasible. Such a strategy
      might abolish the need for a high initial transduction efficiency and might
      result in a gene therapy protocol devoid of the undesirable need for marrow
      ablative treatment of the recipient.

PMID- 9930346
TI  - Intratumoral coinjection of adenoviral vectors expressing IL-2 and IL-12 results
      in enhanced frequency of regression of injected and untreated distal tumors.
AB  - We have studied the ability of adenoviral (Ad) vectors expressing the cytokines
      IL-2 or IL-12 to mediate regression of established tumors in a mouse model of
      mammary adenocarcinoma. Previous results indicated that intratumoral injection of
      vectors expressing IL-2 (AdCAIL-2), or IL-12 (AdmIL-12.1) induced complete tumor
      regression in approximately 30-40% of treated animals. In the current studies, we
      investigated the mechanism of tumor killing in responding animals and the
      efficacy of AdIL-2 and AdIL-12 vector administration in combination compared with
      the use of either vector alone. Animals bearing subcutaneous mammary tumors were
      injected intratumorally with Ad vectors expressing IL-2 or IL-12 or were
      coinjected with both vectors. Animals receiving the combination treatment
      responded substantially better than animals which had received either vector
      alone, with 65% of animals treated with both vectors undergoing complete tumor
      regression. In all three treatment regimens, tumor regression was associated with
      the presence of specific antitumor antigen cytotoxic T-lymphocytes (CTLs), which
      secreted elevated levels of IFN-gamma. Consistent with circulating CTLs being
      involved in regression, when animals bearing bilateral tumors were inoculated in
      a single tumor with IL-2 or IL-12 expressing vectors, both tumors regressed in
      many cases. Again, treatment with both AdCAIL-2 and AdmIL-12.1 was most
      effective, with 63% of animals undergoing complete regression of both treated and
      untreated tumors, compared to 18 or 22% of animals injected with either AdCAIL-2
      or AdmIL-12.1 alone. These data indicate that the combination of IL-2 and IL-12
      is a more effective inducer of antitumor immune responses than either one alone,
      and that the resulting antitumor responses are effective in mediating the
      regression of distal untreated tumors, a property which may aid in the treatment
      of metastatic disease.

PMID- 9930347
TI  - Enhancement by polylysine of transient, but not stable, expression of genes
      carried into cells by polyoma VP1 pseudocapsids.
AB  - Gene transfer to provide long-term expression of a therapeutic product, without
      introducing unwelcome genetic information, is a goal being sought for therapy of
      both hereditary and acquired diseases. Polyoma virus pseudocapsids, generated
      from a VP1-expressing recombinant baculovirus, lack viral DNA and have been
      successfully used to introduce small exogenous genes stably into cells in vitro
      by a process designated 'pseudofection'; although pseudocapsids protect only
      about 3 kbp of exogenous DNA, low efficiency transfer of a larger fragment (6.2
      kbp) has been observed. Here, expression of a 7.2 kbp plasmid (pCMV beta)
      encoding the beta-galactosidase gene was assessed to monitor not only efficiency,
      but the ability of pseudocapsids to transfer larger-sized DNA on their own, or in
      the presence of the polycation, poly-L-lysine, added to protect nonencapsidated
      DNA. When complexed to pseudocapsids only, the efficiency of expression of the
      transferred beta-galactosidase gene (in human or rodent cells), although low,
      appeared to stabilise with time. In the presence of polylysine, unencapsidated
      DNA was shown to be protected against DNase activity, but electron microscopy
      (EM) revealed the formation of large mixed aggregates. The addition of
      pseudocapsids to these aggregates, and measurement of mobilities of the complexes
      in CsCl equilibrum centrifugation, indicated that they contained negligible
      amounts of VP1. For subsequent pseudofection experiments, DNA was complexed first
      with pseudocapsids, then polylysine was added. The latter did not appear to
      displace pseudocapsids from DNA, and was found to increase the efficiency of
      short-term expression both in in vitro and in vivo experiments. Gene expression,
      analysed histochemically or by the polymerase chain reaction, revealed
      transcriptional activity of the input gene, with expression first diminishing,
      then stabilising over time. The presence of pseudocapsids, in complexes with DNA
      with or without polylysine, allowed for stable and persistent gene expression.

PMID- 9930348
TI  - Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured
      mammalian cells.
AB  - Herpes simplex virus type 1 (HSV-1) VP22 was recently reported to mediate
      intercellular trafficking of a protein fused to the C-terminus of VP22. To
      explore the application of such trafficking, we constructed plasmids expressing
      green fluorescent protein (GFP) fused to the C-terminus of either wild-type VP22
      or a 160 amino acid peptide from VP22. In vitro studies showed that the majority
      of both fused proteins were localized to the nuclei of transfected cells.
      Quantitative analysis of GFP-positive cells, however, showed no significant
      increase in intercellular protein trafficking for cells transfected with either
      fusion protein compared with a lacZ-expressing plasmid. Our results suggest that
      the use of HSV-1 VP22 for mediating intercellular trafficking of transgene
      products is limited.

PMID- 9930349
TI  - The size of DNA/transferrin-PEI complexes is an important factor for gene
      expression in cultured cells.
AB  - Under physiological salt concentration, plasmid DNA complexed with transferrin
      conjugated or unmodified polyethylenimine (PEI, 800 kDa) forms huge (up to > 1000
      nm) aggregates, unless the individual components are mixed at a highly positive
      nitrogen/phosphate (N/P) charge ratio. At low ionic strengths, however, small
      particles with an average size of 40 nm are formed over a broad range of N/P
      ratios. Interestingly, in transfection experiments these small particles result
      in a 10-fold (B16F10 cells) to more than 100-fold (Neuro2A cells, K562 cells)
      reduced luciferase gene expression efficiency in comparison to the large
      complexes formed in physiological salt solutions. Limited transport of the small
      particles to the cell surfaces is one possible reason for this effect.
      Application of the small particles in more concentrated form and over extended
      periods of time improves transfection activity. Reduced intracellular release may
      be another explanation for the decreased transfection efficiency; incubation with
      chloroquine or incorporation of the endosomolytic peptide INF5 into the small
      complexes enhances gene expression approximately 10-fold. Analysis of gene
      expression at the cellular level using a green fluorescence protein reporter gene
      and flow cytometry revealed that the differences in overall gene expression
      largely result from different intensities per expressing cell, while the
      difference in the percentage of expressing cells is less substantial.

PMID- 9930350
TI  - Efficient coexpression and secretion of anti-atherogenic human apolipoprotein AI
      and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno
      associated virus plasmid vectors.
AB  - Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT)
      play important roles in reverse cholesterol transport, promoting the removal of
      excess cholesterol from peripheral cells and reducing formation of
      atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are
      thus attractive targets for prevention or treatment of atherosclerosis. With the
      eventual aim of safe and efficient gene delivery to skeletal muscle, our chosen
      secretory platform for systemic delivery of anti-atherogenic proteins, we have
      constructed conventional and AAV-based plasmid vectors containing human apoAI or
      LCAT cDNAs; their efficacy was tested by lipoplex transfection of mouse C2C12
      muscle cells or human 293 cells. The secretion of apoAI or LCAT by transduced
      cultures was two- to five-fold higher using AAV-based plasmid vectors than
      conventional plasmid vectors. Additionally, cells transfected with a bicistronic
      AAV-based vector containing an internal ribosome entry site (IRES) efficiently
      expressed both apoAI and LCAT simultaneously. Furthermore, AAV-based vector
      sequences were retained by host cells, whereas those of conventional plasmid
      vectors were lost. These studies indicate that ectopic overexpression of apoAI
      and LCAT in muscle tissue using AAV-based plasmid vectors might provide a
      feasible anti-atherogenic strategy in vivo.

PMID- 9930351
TI  - The selectable marker neo gene down-regulates gene expression from retroviral
      vectors containing an internal ribosome entry site.
AB  - The internal ribosome entry site (IRES) from the picornavirus family has
      frequently been used to express multiple genes from a polycistronic message in
      retroviral vectors. While examining factors affecting levels of gene expression
      in IRES-containing retroviral vectors, it was found that retroviral vectors
      expressing the two genes linked by IRES, the reporter gene and the selectable
      marker neo, produced significantly lower levels of protein than those containing
      a reporter gene alone. This observation has been made with various cDNA
      sequences. However, when the neo was replaced with a different cDNA, the level of
      gene expression was increased, often to the level achieved with a vector
      expressing a single gene, suggesting that the bacterial neo sequence has a
      negative effect on expression. Analysis of the steady-state RNA levels isolated
      from transfected packaging cells showed that the neo-containing retroviral
      vectors produced significantly lower levels of RNA than those lacking this
      bacterial sequence indicating that neo interferes with expression of the
      neighboring gene at the level of RNA. Furthermore, the order of genes in the IRES
      neo-containing vectors appeared to be more important than in the vector lacking
      the neo sequence. Our results suggest that neo has to be used in the retroviral
      vector with care, especially when a high level gene expression is needed.

PMID- 9930352
TI  - Paraneoplastic pemphigus: a review.
AB  - Paraneoplastic pemphigus (PNP) is a relatively recently described autoimmune
      disorder, distinguished from pemphigus vulgaris or foliaceus by specific
      clinical, histologic and immunologic criteria. In the present review, 18 cases of
      paraneoplastic pemphigus reported so far are discussed. The polymorphism, extent
      and persistence of skin and mucosal lesions are discussed while the problems of
      differential diagnosis and the significance of the associated neoplasms are also
      stressed. The underlying malignancy in the majority of the cases has been of
      lymphoid origin and has preceded the clinical presentation of pemphigus. All
      patients have had oral and cutaneous lesions. In 66.6% of the patients there was
      a poor response to therapy.

PMID- 9930353
TI  - Possible mechanisms by which alcohol may influence the development of oral cancer
      -a review.
AB  - Although pure ethanol has never been shown to be carcinogenic in laboratory
      experiments, alcoholic beverages are now recognised as being important
      aetiological factors in the development of oral cancer. Despite this, the exact
      mechanism by which alcohol may exert an influence upon the oral mucosa has
      received less attention. An overview of the association of alcohol and oral
      cancer, both in combination with tobacco and without, is provided and
      consideration given to some of the pathways by which alcohol exerts its effect
      upon the oral mucosa.

PMID- 9930354
TI  - Molecular piracy: the viral link to carcinogenesis.
AB  - The vast majority of the human experience with viral infections is associated
      with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With
      this acute or lytic phase, the immune system mounts a response and eliminates the
      viral agent while acquiring antibodies to that specific viral subtype. With
      latent or chronic infections, the viral agent becomes incorporated into the human
      genome. Viral agents capable of integration into the host's genetic material are
      particularly dangerous and may commandeer the host's ability to regulate normal
      cell growth and proliferation. The oncogenic viruses may immortalize the host
      cell, and facilitate malignant transformation. Cell growth and proliferation may
      be enhanced by viral interference with tumor suppressor gene function (p53 and
      pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes).
      Overexpression of these oncogenes in viral-infected cells interferes with normal
      cell function and allows unregulated cell growth and proliferation, which may
      lead to malignant transformation and tumour formation. Development of oral
      neoplasms, both benign and malignant, has been linked to several viruses. Epstein
      Barr virus is associated with oral hairy leukoplakia, lymphoproliferative
      disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal
      carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's
      sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic
      lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected
      in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous
      cell carcinoma. The role of human papillomavirus in benign (squamous papilloma,
      focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris),
      premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma)
      neoplasms within the oral cavity is well recognized. Herpes simplex virus may
      participate as a cofactor in oral squamous cell carcinoma development by
      enhancing activation, amplification, and overexpression of pre-existing oncogenes
      within neoplastic tissues. Because of the integral role of viruses in malignant
      transformation of host cells, innovative antiviral therapy may prevent tumour
      development, involute neoplastic proliferations, or arrest malignant progression.

PMID- 9930355
TI  - Oral cancer in the UK: to screen or not to screen.
AB  - Although oral squamous cell carcinoma accounts for only a small proportion of
      malignant neoplasms in the UK, oral cancer incidence and mortality rates have
      been rising in recent years. The natural history of oral cancer is not adequately
      understood at present and there is very little information about the epidemiology
      of precancerous lesions in the UK. There are also insufficient data to provide
      firm evidence that the percentage of cases arising de novo is greater in the UK
      and the Western world as compared to the Indian subcontinent. Screening for oral
      cancer by visual examination is simple, inexpensive and causes little discomfort;
      however, there is no evidence for the effectiveness of screening for oral cancer
      either in reducing mortality from the disease or in reducing the incidence of
      invasive disease by detection and treatment of precancerous lesions. There is
      currently insufficient evidence to recommend population screening for oral cancer
      in the UK. Measures aimed at primary prevention of the disease may be a more
      feasible method of disease control at present.

PMID- 9930356
TI  - The role of FDG PET in the clinical management of head and neck cancer.
AB  - Positron emission tomography (PET) with fluorodeoxyglucose (FDG) allows the
      visualization of metabolic tissue activity. Use of FDG in in-vivo cancer imaging
      is based on enhanced glycolysis in tumor cells. In vivo experiments have
      demonstrated the potential use of FDG PET in squamous-cell head and neck tumors
      and the detection of tumor involvement in lymph nodes. Since its introduction in
      this area, several papers have appeared on the use of this imaging modality.
      Indications for the use of FDG PET in patients with head and neck cancer are
      discussed.

PMID- 9930357
TI  - Surgical management of the neck in squamous cell carcinoma of the floor of the
      mouth.
AB  - Nodal involvement in squamous cell carcinoma considerably lowers survival rate.
      Despite its importance, neck management has still not been adequately explored.
      The Authors have retrospectively reviewed the records of 112 cases. Unilateral N+
      were treated with a homolateral therapeutic and a controlateral prophylactic neck
      dissection; bilateral N+ were treated with a bilateral therapeutic neck
      dissection. On first observation the majority of cases (66.1%) were T1-2, N+
      patients accounted for 45.5%. Among N- patients, 21.3% of occult nodal metastases
      were observed. The 5-year survival rate was 52.7%. With N+ lesions, a radical
      neck dissection should be performed; the dissection should be performed
      bilaterally. With N- lesions a prophylactic modified radical neck dissection is
      recommended in T2-4 lesions.

PMID- 9930358
TI  - The effect of chemotherapy on the supragingival plaque of pediatric cancer
      patients.
AB  - The anaerobic cultivable flora of the dental plaque was investigated in 16 cancer
      children at days 0, 7, 14 and 21 of a first cure of chemotherapy. Results were
      compared with those obtained in 16 healthy children. Diseased children showed
      more quantitative variations of the flora than the controls, especially during
      the first week of chemotherapy. Whatever the day of sampling, the flora of the
      diseased children was significantly less complex than that of the controls.
      Viridans streptococci, Capnocytophaga, and to a lesser extent staphylococci,
      appeared to be the most strongly affected in diseased children. This could be
      explained by different mechanisms, uncontrolled recolonization of the dental
      plaque, selection of multidrug-resistant strains or nosocomial acquisition. These
      results indicate that variations in quantity, complexity and quality of the oral
      flora occur during chemotherapy, leading to a major imbalance of the ecosystem.

PMID- 9930359
TI  - Risk factors associated with mucositis in cancer patients receiving 5
      fluorouracil.
AB  - Oral mucositis is a dose-limiting toxicity of 5-fluorouracil (5-FU). This
      prospective cohort study investigated factors associated with mucositis in
      patients receiving 5-FU for cancer of the digestive tract. Sixty-three patients
      (mean age 65 years) completed self-administered questionnaires and had
      interviews, oral examinations and unstimulated whole salivary flow measurements
      at baseline and follow-up appointments. The duration of follow-up was 2 months.
      Predictor variables included sociodemographic data, body surface area, diabetes,
      smoking, alcohol consumption, salivary flow, oral hygiene, presence of
      prostheses, performance status, regimen of cytotoxic drugs, hematological data,
      and herpes simplex virus antibody titer. Forty-six per cent of patients developed
      at least one episode of oral mucositis during cytotoxic treatment. Pearson's chi
      square analysis showed that mucositis was significantly associated with
      xerostomia at baseline, xerostomia during chemotherapy, and lower baseline
      neutrophil counts (P < or = 0.05). Multiple logistic regression analysis
      indicated that xerostomia at baseline (odds ratio, OR = 10.0), or baseline
      neutrophil level under 4000 cells/mm3 (OR = 3.9) were significant predictors of
      mucositis. Taking into account the effect of neutrophil level at baseline,
      xerostomia during chemotherapy (OR = 4.5) was also a significant predictor of
      mucositis. The results showed that xerostomia and lower baseline neutrophil
      levels are significantly associated with oral mucositis. These variables should
      be taken into consideration in the design of intervention studies to reduce the
      frequency and severity of mucositis. More research is required to investigate the
      role of saliva and neutrophils in the pathogenesis of chemotherapy-induced
      mucositis.

PMID- 9930360
TI  - Staging and IgA VCA titre in patients with nasopharyngeal carcinoma: changes over
      a 12-year period.
AB  - The distributions of 2093 patients with nasopharyngeal carcinoma (NPC), by stage,
      over a 12-year-period did not show any evidence of a shift towards early stages
      despite growing awareness of this prevalent malignancy. The IgA VCA titre was
      determined for 1880 of these patients. The median titre increased from 40 in
      stage I to 80 in stages II, III, and IV, before rising to 160 in stage V. The
      percentage of patients with a titre > or = 320 increased steadily with advancing
      stages. Within the same disease stage, the percentage of patients having a
      particular titre value and the median titre varied considerably from year to
      year. Better education of the general population and a better serological marker
      for screening are needed for the early detection of NPC.

PMID- 9930361
TI  - Expression of 70-kDa heat shock protein in oral lesions: marker of biological
      stress or pathogenicity.
AB  - We showed differential expression of HSP70 during oral tumorigenesis. The precise
      functional role of HSP70 overexpression in the pathogenesis of betel and tobacco
      related oral cancer remains to be determined. To evaluate the utility of HSP70 as
      an indicator of the biological stress experienced by tumour cells or the
      malignant potential of oral epithelial lesions and predicting clinical outcome,
      its expression was assessed in different stages of oral carcinogenesis by
      immunohistochemical analysis and correlated with clinicopathological parameters.
      Overexpression of HSP70 protein was observed in 38 of 64 (59%) dysplastic lesions
      and 92 of 125 (74%) oral squamous cell carcinomas (SCCs) which included 76 of 105
      cases (72%) of primary oral SCCs and 16 of 20 (80%) of recurrent oral SCCs. A
      significant correlation of HSP70 expression was observed with severity of
      dysplasia (P = 0.0006767), poor histological differentiation of primary tumours
      (P = 0.0184348), increase primary tumour size (P = 0.0221103) and consumption of
      betel and tobacco (P < 0.01). Follow-up studies showed that in patients with
      premalignant lesions the median transition time (premalignancy to malignancy) was
      significantly shorter in HSP70 overexpressing cases than those showing basal
      level of HSP70 (P = 0.012). Oral cancer patients with elevated levels of HSP70
      showed decreased median disease-free survival time (no recurrence/metastasis)
      than those showing basal HSP70 immunoreactivity (P = 0.0246). The results suggest
      that HSP70 expression may not be a mere marker of biological stress but may also
      be implicated in the pathogenesis of oral cancer.

PMID- 9930362
TI  - Immunohistochemical analysis of a dentinogenic ghost cell tumour.
AB  - A dentinogenic ghost cell tumour in an 80-year-old male patient is presented. It
      is an extremely rare tumour and only 10 cases have been reported in the English
      literature. The lesion showed odontogenic epithelium, ghost cells, dentinoid,
      giant cells. The immunohistochemical analysis for Mib-1 and bel-2 showed a strong
      positivity of the cells of the odontogenic epithelium, while with p53 only a rare
      positivity was observed. Completely negative were the ghost cells, giant cells
      and dentinoid material. In this tumour the cells expressing Mib-1 and bcl-2 could
      be the cells that proliferate, and that could undergo malignant transformation.

PMID- 9930363
TI  - Genomic alterations in oral squamous cell carcinoma cell lines detected by two
      dimensional gel analysis.
AB  - To initially analyze the genomic abnormalities in human oral squamous cell
      carcinoma, DNA extracted from each of four oral carcinoma cell lines (Ca9-22, HO
      1-u-1, HSC-2, KB) was examined using restriction landmark genomic scanning
      (RLGS), a method especially conducive to detection of amplifications and
      rearrangements of genomic DNA. Isolated cell line and normal oral epithial DNAs
      were sequentially cleaved with specific restriction enzymes, radiolabelled and
      separated in two-dimensional gel electrophoreses. Thirteen distinct fragments
      were commonly amplified in the oral cancer cell lines, six of which were evident
      in all samples. These results suggest genetic alterations characteristic of oral
      squamous cell carcinogenesis.

PMID- 9930364
TI  - An analysis of the prognostic significance of p53 status for squamous cell
      carcinoma of the oral cavity treated by radiotherapy.
AB  - The status of the p53 gene in biopsy specimens was analyzed to determine whether
      it is predictive of the outcome of radiotherapy of squamous cell carcinomas of
      the oral cavity. Biopsy materials were obtained from 45 patients, and the p53
      status of each patient was determined using a single-strand conformation
      polymorphism analysis. Fourteen of the patients were treated with radiation
      therapy alone; the other 31 patients underwent radiotherapy in combination with
      surgery or chemotherapy. Twenty-seven patients had tumors with wild-type p53 and
      18 patients had a tumor with mutant p53. The initial tumor response was not
      significantly different between these two groups. Kaplan-Meier survival plots
      (log-rank test) showed that the probability of survival was not significantly
      different between two groups although the patients with mutant p53 had a tendency
      for longer survival (P = 0.2941). However, among the patients with stage III/IV
      tumors (n = 24), those with a wild-type p53 status tended to have longer
      survivals.

PMID- 9930365
TI  - Loss of heterozygosity at 8p, 9p and 17q in laryngeal cytological specimens.
AB  - The activation of oncogenes and the inactivation of tumour suppressor genes play
      a critical role in laryngeal tumorigenesis. Recent investigations revealed that
      8p, 9p and 17q arms of human chromosomes harbour tumour suppressor genes (TSGs)
      such as p16 and BRCA1 with an important role in the multistage carcinogenesis of
      the larynx. In order to investigate the implication of these novel TSGs in the
      development of laryngeal neoplasia we performed a loss of heterozygosity (LOH)
      analysis using a bank of 15 polymorphic microsatellite markers (4 at 8p21, 7 at
      9p21 arm and 4 at 17q arm surrounding the BRCA1 region) in a series of 32
      cytological specimens (19 squamous cell carcinoma, 13 benign lesions of the
      larynx). Both benign and malignant specimens exhibited genetic alterations with
      at least one microsatellite marker. Fifteen (47%) out of the 32 specimens
      exhibited LOH at 8p21, 25/32 (78%) showed LOH at 9p21 and 18/32 (56%) displayed
      LOH at 17q21. Genetic alterations were detected in both benign and malignant
      lesions for all the loci tested suggesting an important role of these regions in
      the development of laryngeal neoplasia. This is the first report of detection of
      microsatellite alterations not only in solid tumours of the larynx but in
      laryngeal cytological specimens, suggesting that microsatellite analysis may be a
      useful tool in the primary diagnosis of the disease.

PMID- 9930366
TI  - Increased expression of human DNA repair genes, XRCC1, XRCC3 and RAD51, in
      radioresistant human KB carcinoma cell line N10.
AB  - The radioresistant N10 and parental KB cell lines were examined for the
      expression of human DNA repair genes which were related to the repair of
      radiation-induced DNA damage by northern blot analysis using five kinds of DNA
      probes (XRCC1, XRCC3, XRCC5, RAD51, RAD52). In the unirradiated condition, N10
      cells showed higher expression of XRCC1, XRCC3 and RAD51 mRNA than did KB cells.
      The X-irradiation induced a time-dependent increase in the mRNA levels of XRCC3
      and RAD51 in both cell lines with a maximum at 2 h postirradiation. The XRCC1
      mRNA in N10 was maintained at the same level even after irradiation, whereas that
      in KB was decreased after irradiation. There was no difference in the expression
      of XRCC5 and RAD52 mRNA between N10 and KB cells in both unirradiated and
      irradiated conditions. From these findings, it was suggested that XRCC1, XRCC3
      and RAD51 contribute to the radioresistance in cell line N10.

PMID- 9930367
TI  - p53- and p21-independent apoptosis of squamous cell carcinoma cells induced by 5
      fluorouracil and radiation.
AB  - Apoptosis-inducing therapy is becoming a new strategy in cancer therapy. We
      investigated the influence of 5-fluorouracil (5-FU) and radiation (gamma-ray) on
      the cell cycle of tumor cells, and their apoptosis-inducing activity using four
      oral squamous cell carcinoma lines (OSC-1 and OSC-4 with wild type p53; OSC-2 and
      OSC-3 with mutant type p53). The expression of p53 and cyclin-dependent kinase 2
      (Cdk2) proteins was not increased even after cell treatment with 5-FU and gamma
      rays in any cell lines. Although the promoter of p21 gene was not activated, p21
      mRNA expression was increased by 5-FU and gamma-rays. p21 protein was expressed
      by irradiation in parallel with the increase in the messages but not by 5-FU in
      any OSC lines. Despite the increased p21 protein expression, cyclin E/Cdk2 kinase
      activity was not suppressed in irradiated cells. With the increased expression of
      cyclin E protein, 5-FU augmented the kinase activity in OSC-1, OSC-2 and OSC-3
      cells. However, with a constant cyclin E level the kinase activity in OSC-4 was
      not increased by 5-FU. Without correlation to the kinase activity, 5-FU strongly
      induced apoptosis in OSC-2, OSC-3 and OSC-4 accumulating cells in the S phase,
      but 5-FU only very weakly induced apoptosis in OSC-1. While irradiated cells were
      in the G2/M phase, they exhibited apoptosis, to the same degree, in all OSC
      lines. Furthermore, the expression of Bax protein was not increased by 5-FU or
      gamma-rays, although apoptosis was induced by both treatments. These findings
      indicate that 5-FU and gamma-rays induce apoptosis of squamous cell carcinoma
      cells in p53- and p21-independent manners, in the S and G2/M phases,
      respectively.

PMID- 9930368
TI  - Antizyme prevents ornithine decarboxylase-mediated cell death in human
      fibroblasts.
AB  - Ornithine decarboxylase (ODC) is a key enzyme of polyamine biosynthesis essential
      for growth-related cellular functions. Apart from its physiological role in cell
      proliferation, ODC also contributes to the induction of apoptosis under certain
      conditions, e.g. following growth factor withdrawal. The rate of cell death is a
      function of its enzyme activity, ODC activity is inhibited by a regulatory
      protein antizyme, also known to suppress polyamine uptake. We report that forced
      expression of antizyme prevents ODC-mediated cell death in human gingival
      fibroblasts under very low serum conditions. These data suggest an important
      antiapoptotic role for antizyme in cell survival.

PMID- 9930369
TI  - Angiogenesis during tumor progression in the oral cavity is related to reduced
      apoptosis and high tumor cell proliferation.
AB  - Angiogenesis, the growth of new blood vessels, is believed to aid tumor
      progression and metastasis. Tumor progression is also influenced by the extent of
      proliferation and apoptosis. This study, therefore, analyzed in lesions of the
      oral cavity, the significance of angiogenesis in relation to apoptosis,
      expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue
      proliferation defined by cyclin D1 expression. Results from this study suggest
      that angiogenesis increases as histological abnormality increases in the oral
      mucosa. The expression of apoptosis regulatory proteins also appears to be
      altered in a histologically dependent manner. The correlation seen between CD34
      expression, cyclin D1 and TUNEL reactive cells suggests that increased
      angiogenesis, decreased apoptosis and deregulated proliferation occur
      simultaneously during tumor progression in the oral mucosa. Presence of a mutant
      p53, increased bcl-2 expression and altered bax expression are also involved in
      this complex process.

PMID- 9930370
TI  - A novel evaluation system of metastatic potential of oral squamous cell carcinoma
      according to the histopathological and histochemical grading.
AB  - We established a new evaluation system for metastatic potential of oral squamous
      cell carcinoma (SCC), utilizing a combined examination of histopathological
      grades of the carcinomas based on cell differentiation and invasive mode
      according to Yamamoto's criteria, and the cellular expressions of CD44, E
      cadherin (E-cad), heparan sulfate glycosaminoglycan (HS-GAG) and Phaseolus
      vulgaris leukoagglutinin (L-PHA)-binding oligosaccharides on the carcinomas.
      Histochemical patterns of expression of these markers were classified into
      positive (+2), weakly positive (+), and negative (-). The histopathological
      grades and the histochemical patterns of the SCC were estimated on a 0-2 point
      scale, i.e. point 2 for poorly differentiated, mode 4D, CD44++, E-cad-, HS-GAG++,
      or L-PHA++; point 1 for moderately differentiated, mode 4C, CD44+, E-cad+, HS
      GAG+, or L-PHA+; and point 0 for well differentiated, mode 1, mode 2, mode 3,
      CD44-, E-cad++, HS-GAG-, or L-PHA-. As a result, incidence of metastasis in the
      cases with a total score of more than 6 (62.8%) was significantly higher than
      that with a total score of less than 5 (9.3%). This evaluation system will yield
      useful information concerning the prognosis of patients with oral SCC.

PMID- 9930372
TI  - Paraneoplastic pemphigus as the presenting symptom of a lymphoma of the tongue.
AB  - A patient is described who initially presented with an acrovesicular eczema which
      subsequently developed into erythema multiforme with histopathological features
      of bullous pemphigoid. Although the various laboratory studies pointed to the
      diagnosis of paraneoplastic pemphigus (PNP), the underlying neoplasm was not
      detected until 6 months later, when the biopsies of an oral lesion showed the
      presence of an underlying non-Hodgkin lymphoma.

PMID- 9930371
TI  - The Swedish snus and the Sudanese toombak: are they different?
AB  - In Sweden, snuff (locally known as snus), was introduced since the year 1637.
      Presently, Sweden has the highest per capita consumption and sale figures of
      snuff in the world, and the habit is becoming increasingly popular. Snus is
      manufactured into a dry form used in the nasal cavity and a moist form used in
      the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark
      Kentucky or Virginia species mixed with an aqueous solution of water and other
      blending ingredients. This form of snuff is found in two types: (1) loose and (2)
      portion-bag-packed. These are the most widely used. The loose moist form (1-2 g a
      quid) is the most popular type consumed by 73% of the males, followed by the
      portion-bag-packed form (0.5-1 g a quid), consumed by 13% of the males, while 14%
      of the males are mixed users. The majority of snus users place the quid in the
      vestibular area of the upper lip, and the prevalence among persons 15 years of
      age or older in 15.9% among males and 0.2% among females. The pH of snus has
      declined from a previous range of 8-9 to a range of 7.8-8.5, moisture content
      ranges 35-60% and nicotine content is in the order of 5-11 mg/g dry wt tobacco
      specific N-nitrosamines (TSNAs) in micrograms (N'-nitrosonornicotine: NNN 5-9; 4
      (methyl-nitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1-2; N'-nitrosoanatabine: NAT
      2-5). In the Sudan, snuff, locally known as toombak, was introduced approximately
      400 years ago. It is always processed into a loose moist form, and its use is
      widespread in the country. Tobacco used for manufacture of toombak is of the
      species Nicotiana rustica, and the fermented ground powder is mixed with an
      aqueous solution of sodium bicarbonate. The resultant product is moist, with a
      strong aroma, highly addictive and its use is widespread particularly among
      males. Its pH range is 8-11, moisture content ranges 6-60% and nicotine content
      is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420-1 550;
      NNK 620-7 870; NAT 20-290). Snus and toombak dippers develop a clinically and
      histologically characteristic lesion at the site of dipping. Probably due to
      control of the TSNAs in snus, this type of snuff is associated with a lower risk
      of cancer of the oral cavity (relative risk: RR 5-6-fold), whereas the risk for
      cancer of the oral cavity among toombak users was high (RR 7.3-73.0-fold). In
      conclusion, the two snuff products significantly differ in many aspects. Most
      notable differences are tobacco species, fermentation and ageing, nicotine and
      TSNAs content, pH, expression of the p53 tumour suppressor gene, and keratin
      types 13, 14, and 19. It was, therefore, the object of the present study to
      highlight the oral health hazards of toombak, and to compare it with snus
      regarding the aforementioned differences.

PMID- 9930373
TI  - Paraneoplastic pemphigus: a report of two cases.
AB  - Paraneoplastic pemphigus (PNP) seems to be a separate autoimmune mucocutaneous
      disease. Forty-five cases have been reported. Almost all cases of PNP are
      associated with a tumour, mostly with haematologic malignancies. Pemphigus-like
      autoantibodies are detected by direct and by indirect immunofluorescence studies.
      These autoantibodies appear to be directed against a novel set of autoantigens.
      Two cases are presented with clinical, histologic, immunofluorescence and
      immunoprecipitation findings characteristic of PNP.

PMID- 9930374
TI  - Oral cancer versus oropharyngeal cancer versus head and neck cancer.

PMID- 9930375
TI  - Action of angiotensin receptor subtypes on the renal tubules and vasculature:
      implications for volume homeostasis and atherosclerosis.
AB  - Angiotensin-II (ANG-II) is a potent endocrine and paracrine hormone that
      functions in humans through two distinct G-protein-coupled transmembrane receptor
      subtypes (AT-1 and AT-2). ANG-II is found in nearly all tissues of the body
      including the brain, heart, kidneys, gonads, and gastrointestinal tract. Just as
      it is found in nearly every organ system of the body, so is it involved in an
      array of physiologic processes from fetal development to blood pressure control.
      ANG-II regulates blood pressure by controlling sodium reabsorption in the
      proximal tubule, altering the glomerular filtration rate and renal blood flow,
      and by modifying the production and release of aldosterone in the adrenal gland.
      Additionally, ANG-II is involved in several pathologic processes including the
      development of hypertension, cardiomyopathy, atherosclerosis, and diabetic
      nephropathy. It is able to exert influences in these widely varying processes by
      working together with multiple different second messenger systems including the
      MAP kinase pathway, nitric oxide production, and phospholipase C and D, and
      several arachidonic acid metabolites. This paper is a review of the current
      knowledge of ANG-II and its receptors in health and disease.

PMID- 9930376
TI  - Control of renal function and blood pressure by angiotensin II: implications for
      diabetic glomerular injury.
AB  - A principal, and unique, renal effector site for angiotensin II (ANG II) is the
      efferent arteriole, and that has generated considerable interest regarding
      potential benefits of ANG II inhibition in the treatment and prevention of
      diabetic renal injury. A hallmark complication of long-standing diabetes is
      glomerular injury, and there is substantial evidence that lowering glomerular
      hydrostatic pressure attenuates the injury process. One way that has been
      accomplished is by lowering arterial pressure, but additional evidence suggests
      that anti-hypertensive treatment with ANG II inhibition provides even greater
      protection because of the associated efferent arteriolar dilation. Because of
      that action, ANG II inhibition in diabetes has been advocated even without
      diagnosis of hypertension, and the benefits of that treatment have been ascribed
      largely to the effect of decreased efferent arteriolar resistance to lower
      glomerular hydrostatic pressure. However, that renal vascular action of ANG II,
      together with powerful direct effects on tubular sodium reabsorption, underlie
      its dominant influence on chronic arterial pressure control. Moreover, the
      influence of ANG II on arterial pressure is not limited to hypertension; it
      contributes significantly to the maintenance of blood pressure when plasma ANG II
      levels are normal or even reduced. Thus, while acknowledging that efferent
      arteriolar dilation is a unique intrarenal benefit associated with ANG II
      inhibition, this review will focus on how and why inhibition of the multiple
      intrarenal actions of ANG II also protect the kidneys through systemic
      mechanisms, even when blood pressure and ANG II are not increased.

PMID- 9930377
TI  - The renin-angiotensin system in diabetic nephropathy: the endothelial connection.
AB  - In recent years endothelial function has been forwarded a modulator in the
      pathogenesis of diabetic nephropathy. This review summarizes how an imbalance
      between endothelium-derived reactive nitrogen species and reactive oxygen species
      as well as increased expression of the endothelium-derived peptide endothelin-1
      may contribute to loss of renal function in diabetes. In addition, the
      potentially beneficial effects of blockade of the renin-angiotensin system on
      this endothelial dysbalance is discussed.

PMID- 9930378
TI  - Interaction of the renal amylin and renin-angiotensin systems in animal models of
      diabetes and hypertension.
AB  - The range of known actions of amylin are reviewed together with the proposal that
      an important role for amylin may be the hormonal integration of diverse
      physiological systems activated with feeding. Major targets for the action of
      amylin are found within the kidney. Components of the amylin system (AS) have
      been shown to influence the activity of components of the renin-angiotensin
      system (RAS), and vice versa, in normal, hypertensive and diabetic models. For
      instance, amylin injected into humans and rats elicits a rapid rise in plasma
      renin activity. Furthermore, in two models of hypertension (the spontaneously
      hypertensive rat (SHR) and the model with subtotal nephrectomy (STNx)), the
      density of amylin-binding sites in the renal cortex associated with the proximal
      tubules, was associated with elevation of blood pressure. In normotensive
      controls and in the STNx model, but not in the SHR model, treatment with
      angiotensin-converting enzyme (ACE) inhibitors reduced blood pressure and the
      density of amylin binding in the renal cortex. In Sprague-Dawley rats,
      angiotensin II (Ang II) infusion was associated with increased density of amylin
      binding sites as well as elevated blood pressure. Thus, there appears to be a
      direct relationship between the activity of Ang II and the binding sites for
      amylin in the renal cortex. From these studies it has been postulated that the
      activation of the AS in the kidney may play a role in the genesis and/or
      development of hypertension in certain contexts. The transient expression of
      amylin mRNA has been detected perinatally, using in situ hybridization, in the
      subnephrogenic zone of the metanephros and is associated with proximal tubules of
      the developing nephron. These cells situated close to the glomeruli, represent a
      subset of brush border epithelial cells. Amylin immunoreactivity (IR) is also
      found in these cells and colocalizes with angiotensinogen IR. Thus a second
      important role for amylin is described in which it plays a role as a growth
      factor in the developing kidney and in renal regrowth in the adult kidney. In a
      model of IDDM (streptozotocin diabetes), amylin and angiotensinogen IR are both
      restricted to a subset of brush border epithelial cells close to glomeruli which,
      in the developing kidney, expressed amylin mRNA. Thus in this IDDM model, we
      hypothesize that amylin mRNA transcription which is normally downregulated in the
      adult, is upregulated in this subset of these brush border epithelial cells, and
      that it stimulates the activity of a local RAS by an intracellular mechanism,
      leading to the biosynthesis of Ang II. It remains to be determined that if amylin
      is playing a role in stimulating local Ang II production at these sites, this
      provides a mechanism for activation of TGF-beta, ultimately leading to
      interstitial fibrosis.

PMID- 9930379
TI  - A potential role for angiotensin II-induced vascular endothelial growth factor
      expression in the pathogenesis of diabetic nephropathy?
AB  - Diabetic nephropathy often co-exists with other manifestations of
      microangiopathy, in particular retinopathy. Recent clinical evidence suggests
      that inhibition of the renin-angiotensin system in humans can delay the
      development and/or progression of diabetic nephropathy and perhaps also
      retinopathy. The benefits of this therapeutic strategy may in part be explained
      by inhibition of the nonhaemodynamic actions of angiotensin II (Ang II). The
      recognized nonhaemodynamic actions of Ang II include the augmented release of
      many growth factors. Ang II can stimulate the release of vascular endothelial
      growth factor (VEGF) from human vascular tissues. VEGF is a family of potent
      cytokines which act to induce angiogenesis and markedly increase microvascular
      permeability. VEGF is abundantly expressed in the renal glomerulus, specifically
      within the podocyte, where its function is unknown. VEGF is also expressed in the
      retina and increased retinal VEGF expression occurs in diabetes and has been
      implicated in the pathogenesis of diabetic retinopathy. This review considers the
      potential clinical significance of Ang II-induced VEGF expression, if any, in the
      pathogenesis of diabetic nephropathy and retinopathy.

PMID- 9930380
TI  - Physiologic actions and molecular expression of the renin-angiotensin system in
      the diabetic rat.
AB  - Clinical, experimental, biochemical, and molecular biologic studies all invoke an
      important role for the renin-angiotensin system (RAS) in the pathogenesis of
      diabetic complications. Studies of pharmacologic interruption of the RAS with
      angiotensin-converting enzyme (ACE) inhibition have implicated this hormonal
      system in the progression of diabetic nephropathy, both experimentally and
      clinically. Preliminary evidence also suggests a beneficial effect of angiotensin
      II (Ang II) receptor antagonists. The relative roles of the systemic vs.
      intrarenal RAS in the pathogenesis of diabetic nephropathy have recently been
      evaluated. Though plasma renin is generally low, it is not yet clear whether RAS
      component processing is normal in diabetes; there may be subtle changes in Ang II
      metabolism which sustain relatively higher plasma Ang II levels. Furthermore, the
      intrarenal RAS may not be suppressed. Renal renin levels tend to be
      disproportionately elevated, as compared to plasma renin values. Renal Ang II
      levels are normal, and renal mRNAs for RAS components have been variable, though
      not suppressed. In general, lack of RAS suppression (despite plasma volume and
      increased exchangeable sodium) may indicate inappropriate activity of the RAS in
      diabetes. Indeed, disproportionate activity of the intrarenal RAS may be a
      proximate cause of the observed suppression of the systemic RAS. RAS-mediated
      injury may occur via stimulation of a number of sclerosing mediators, and there
      is evidence that hyperglycemia acts synergistically with Ang II to promote
      cellular injury. Together, these recent investigations lend further support to
      the notion that the RAS plays an important role in diabetic nephropathy, and are
      beginning to shed light on the mechanisms of progressive renal injury.

PMID- 9930381
TI  - Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular
      disease and cardiomyopathy.
AB  - Diabetes mellitus is associated with an inordinately high risk of virtually all
      manifestations of cardiovascular-renal disease including atherosclerotic coronary
      and peripheral vascular disease, congestive heart failure, stroke, nephropathy,
      and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the
      renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the
      pathogenesis and clinical expression of these cardiovascular-renal sequelae.
      Thus, pharmacological modulation of the RAAK system is an attractive therapeutic
      target in diabetes mellitus. Indeed, emerging data from human clinical studies
      appear to confirm this thesis.

PMID- 9930382
TI  - Differences in renal outcomes with ACE inhibitors in type 1 and type 2 diabetic
      patients: possible explanations.
AB  - In type 1 diabetic patients, ACE inhibitors exert a renoprotective effect which
      appears to be additional to, but not entirely independent of, changes in systemic
      blood pressure. This effect includes attenuation of albumin excretion rate (AER)
      as well as prevention or slowing of the rate of decline of the glomerular
      filtration rate (GFR). In type 2 diabetic patients, the results of ACE inhibition
      are more varied with some studies showing similar renoprotection to that observed
      in type 1 diabetes and others showing no additional effect to lowering of
      systemic blood pressure. This may be due to the diverse manifestations of the
      disease itself or to renal factors which may modify the response to ACE
      inhibitors. The major systemic causes of diversity are variations in age, race
      and blood pressure. The major renal causes of diversity include changes in the
      relationship or 'coupling' of AER to onset of decline in GFR and a heterogeneity
      of renal ultrastructural changes in the glomeruli, tubules, interstitium and the
      renal vasculature. Factors that may be responsible for different renal responses
      to ACE inhibitors in type 2 diabetes include coexistence of coronary heart
      disease which may introduce survival bias in long-term studies, a lower
      specificity of microalbuminuria for diabetic nephropathy, early onset of a
      decline in GFR in hypertensive or normotensive patients at or prior to the onset
      of microalbuminuria, a greater contribution of arteriosclerotic changes in renal
      arteries to decline in renal function, a higher prevalence of nondiabetic renal
      disease, a higher prevalence of hypertension in the elderly and yet to be
      characterized genetic factors. These variants of type 2 diabetes may be expected
      to influence the response to ACE inhibitors either by altering the initial
      proteinuric response or by altering the hypotensive response. Future studies
      taking into account the above variables may help to determine the relative
      importance of the above factors in modifying the renal responses to ACE
      inhibitors and thereby leading to different renal outcomes in type 1 and type 2
      diabetic patients. Such studies may also help to assess the relative importance
      of changes in systemic blood pressure and intrarenal effects as well as the role
      of hemodynamic versus structural factors in contributing to differences in renal
      outcome with ACE inhibitors in type 1 and type 2 diabetes.

PMID- 9930383
TI  - Impact of salt intake on blood pressure and proteinuria in diabetes: importance
      of the renin-angiotensin system.
AB  - Patients with hypertension and diabetes are frequently salt-sensitive.
      Consequently, increasing dietary salt intake results in a rise in systemic
      arterial pressure and an increase in proteinuria, as well as a progressive risk
      for developing renal injury. A difference in the renal hemodynamic response to
      salt appears, at least in part, to determine how the salt intake affects blood
      pressure. Greater dietary salt intake in salt-sensitive patients results in a
      blunted rise in renal plasma flow and an increase in body weight. Greater dietary
      salt consumption also results in a rise in glomerular filtration fraction and
      increasing proteinuria. Pharmacologic antagonism of the renin-angiotensin system
      helps restore the blunted renal plasma flow response to high salt intake and
      correlates with the fall in mean arterial pressure. Consequently, the pressor
      response to increasing dietary salt consumption in patients with diabetes and
      hypertension may be related to insufficient renal vasodilation, perhaps due to
      inadequate suppression of the renin-angiotensin system. Moreover, inadequate
      suppression of the renin-angiotensin system within the kidney results in an
      increase in efferent glomerular arteriolar tone and a rise in glomerular
      capillary pressure, increased proteinuria and a greater risk for renal injury.
      Many of the coexisting cardiovascular risk factors associated with salt
      sensitivity may be explainable in part by the overactivity of the renin
      angiotensin system.

PMID- 9930384
TI  - Vancomycin-resistant Enterococcus.

PMID- 9930385
TI  - Comparison of the effect of lansoprazole and omeprazole on intragastric acidity
      and gastroesophageal reflux in patients with gastroesophageal reflux disease.
AB  - BACKGROUND: Lansoprazole (LAN) and omeprazole (OME) heal esophagitis effectively
      and to similar extents, but LAN has a faster effect on the relief of symptoms of
      gastroesophageal reflux. However, no strict comparison of the two proton pump
      inhibitors' effect on acid reflux and gastric acidity has been published. The aim
      of this study was to compare the effects of LAN and OME on gastroesophageal
      reflux with simultaneous measurements of gastric acidity in patients with
      established gastroesophageal reflux disease (GERD) and esophagitis. METHODS:
      Fourteen patients with endoscopically verified erosive esophagitis and with a
      pretreatment esophageal 24-h pH measurement showing acid reflux to the esophagus
      participated in the study. This was a double-blind, randomized study with
      crossover design. Before (day 0) and on the last day (day 5) of each treatment
      period with encapsulated 30 mg LAN or 20 mg OME daily, 24-h intraesophageal and
      intragastric acidity were measured with antimony electrodes connected to an
      ambulatory pH recording system. RESULTS: Ten of 14 patients completed the study.
      There were no differences in intragastric or intraesophageal acidity or the
      number of reflux episodes on day 0 between the two treatments. Both LAN and OME
      treatments increased the median and nocturnal intragastric pH and decreased the
      24-h area under the time curve for intragastric acidity significantly and to
      about the same extent (79% and 69% acid inhibition by LAN and OME, respectively)
      (NS). However, the percentage of time with pH below 4 in the esophagus was
      significantly less during LAN treatment (1.92% +/- 2.29; mean +/- standard
      deviation) than during OME treatment (4.76% +/- 2.88%) on day 5 (P = 0.002).
      There were also significantly fewer reflux episodes >5 min during treatment with
      LAN (1.00 +/- 1.33) than with OME (2.90 +/- 2.42) at the end of the treatment
      period (P = 0.031). CONCLUSIONS: In this study lansoprazole and omeprazole had a
      comparable effect on gastric acidity in patients with established GERD with
      esophagitis. However, 30 mg lansoprazole daily reduced the acidity in the
      oesophagus and the number of refluxes more effectively than 20 mg omeprazole
      daily. This might indicate that proton pump inhibitors affect the esophageal
      clearance and/or influence the lower esophageal sphincter differently.

PMID- 9930386
TI  - Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor
      antagonists in Helicobacter pylori-negative patients.
AB  - BACKGROUND: Treatment with H2 receptor antagonists (H2RAs) and proton pump
      inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecretion of
      gastric acid after treatment, and during treatment with H2RAs tolerance develops.
      In the present study we investigated whether a treatment period with a PPI
      induced tolerance to an H2RA. METHODS: Thirteen patients with esophagitis were
      given omeprazole for 90 days. Twenty-four-hour pH monitorings without and with
      ranitidine were performed before and after treatment with omeprazole. Blood
      samples and biopsy specimens from the oxyntic mucosa were analyzed for gastrin,
      histamine, and chromogranin A. RESULTS: An increase in mucosal histamine and a
      reduction in the effect of ranitidine on gastric pH was found 14 days after
      discontinuing omeprazole compared with before treatment in Helicobacter pylori
      negative but not in H. pylori-positive patients. CONCLUSIONS: Treatment with
      omeprazole reduces the effect of ranitidine in H. pylori-negative patients. This
      is caused by an increase in histamine released by the enterochromaffin-like cell
      secondarily to hypergastrinemia, corresponding to the tolerance towards H2RAs
      seen in patients with Zollinger-Ellison syndrome.

PMID- 9930387
TI  - Interleukin-8 expression by human neutrophils activated by Helicobacter pylori
      soluble proteins.
AB  - BACKGROUND: Helicobacter pylori soluble proteins may serve as chemoattractants
      for neutrophils. Once extravasated and attracted to the gastric mucosa,
      neutrophils themselves may be a source of interleukin-8 (IL-8), further
      amplifying the inflammatory response. We evaluated IL-8 expression and the
      activation of human neutrophils by H. pylori products. METHODS: After neutrophils
      had been stimulated with H. pylori culture supernatant, IL-8 mRNA expression was
      assessed by quantitative reverse transcription polymerase chain reaction, using
      synthetic standard RNA at 0, 1, 2, 4, and 9 h. The amount of IL-8 protein was
      measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte function
      associated antigen-1beta (LFA-1beta) (CD18) expression was determined with flow
      cytometry, and myeloperoxidase secretion was analyzed with ELISA. After
      acetohydroxamic acid (AHA) and/or N-tert-butoxycarbonyl-methionyl-leucyl
      phenylalanine (BOC-MLP) was added to H. pylori culture supernatant, IL-8 ELISA
      was analyzed for 9 h. RESULTS: IL-8 mRNA expression by stimulated neutrophils was
      16 to 67 times greater than by controls, peaking at 2 h after stimulation. The
      amount of IL-8 protein was markedly increased at 4 h after stimulation. H. pylori
      culture supernatant enhanced LFA-1beta expression and myeloperoxidase secretion
      by neutrophils. AHA and/or BOC-MLP decreased IL-8 production at 2-4 h after
      stimulation. CONCLUSIONS: H. pylori-induced neutrophil recruitment may be
      mediated via IL-8 expressed by neutrophils activated by H. pylori soluble
      proteins. This may explain the gastric mucosal inflammatory response to the non
      invasive organism.

PMID- 9930388
TI  - Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA-
      and CagA-independent pathway in rats.
AB  - BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective
      mechanisms. Such effects could be due to a direct interaction with gastric
      epithelial cells but also to the action of a wide range of secreted and membrane
      bound virulence factors. Our aim was to study the acute effects of water extracts
      produced from H. pylori on gastric mucosal blood flow and acid secretion and to
      relate them to VacA and CagA activity. METHOD: Extracts were produced from
      strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking
      expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen
      (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied
      on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after
      removal of as much as possible of the mucus layer, during intravital microscopy.
      Blood flow was measured by means of laser-Doppler flowmetry. RESULTS: All H.
      pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30
      min, significantly reduced blood flow by 15%-19%, whereas E. coli had no
      significant effect on blood flow. CONCLUSION: A factor or a combination of
      factors, other than VacA and CagA released from H. pylori, might compromise the
      natural defence of the gastric corporal mucosa by reducing mucosal blood flow.
      The factor is heat-stable and lacking or less potent in E. coli.

PMID- 9930389
TI  - Classification of dyspepsia. Identification of independent symptom components in
      7270 consecutive, unselected dyspepsia patients from general practice.
AB  - BACKGROUND: Several attempts to classify dyspepsia into subgroups have been
      proposed as a basis for empirical treatment and research. However, subgrouping
      has proved difficult due to overlap of symptoms between subgroups, and the
      response to empirical therapy is difficult to predict. We aimed to study whether
      natural symptom combinations occur in patients seeing general practitioners
      because of dyspepsia and whether symptom presentation could predict the effect of
      proton pump inhibitor treatment. METHODS: The symptom presentation of 7270
      consecutive, unselected patients with dyspepsia in general practice was studied
      by using principal-components analysis. The relation to the effect of omeprazole
      was studied in a subsample (n=471) with predominantly reflux-like or ulcer-like
      dyspepsia being included in a controlled clinical trial of omeprazole versus
      placebo. RESULTS: Four principal components (factors), explaining 36% of the
      total variance, were found. They describe four independent dimensions in the
      symptoms of dyspepsia that can be interpreted meaningfully as representing A)
      acid-related disease of the upper gastrointestinal tract, B) irritable bowel
      disorder, C) dysmotility of the stomach/duodenum, and D) dysmotility of the
      esophagus. In the subsample the response to proton pump inhibition therapy was
      associated with high component-A scores, low component-B scores, and low
      component-C scores. A pocket chart was devised to obtain the component scores
      easily in new patients. CONCLUSION: The analysis identified four characteristic,
      biologically meaningful dyspepsia components that express independent dimensions
      in the symptoms of patients with dyspepsia. The symptom scores corresponding to
      the four components may improve symptom-based diagnosis and thereby empirical
      therapy. In particular, the association between component scores and the effect
      of omeprazole suggests that classifying dyspepsia on the basis of these
      components may focus empirical omeprazole therapy even more.

PMID- 9930390
TI  - Constipation assessed on the basis of colorectal physiology.
AB  - BACKGROUND: Constipation is a collective term for symptoms of different
      aetiologies and pathophysiologies. Our aim was to determine the prevalence of
      colorectal pathophysiology findings in a prospective series of patients with
      chronic constipation. METHODS: A total of 155 consecutive patients with chronic
      constipation underwent anorectal manometry, electromyography (EMG), the balloon
      expulsion test, colonic transit-time study, and defecography. RESULTS: All
      investigations were completed by 134 patients (112 females) with a median age 52
      (range, 17-79) years. Patients were categorized on the basis of transit time and
      pelvic-floor function as belonging to 1 of 4 groups: slow-transit constipation
      (STC) (delayed transit time but normal pelvic-floor function, n = 28), pelvic
      floor dysfunction (PFD) (pelvic-floor dysfunction and normal transit time, n =
      32), combined slow transit and pelvic-floor dysfunction (STC + PFD) (n = 27), and
      normal-transit constipation (NTC) (normal transit time and normal pelvic-floor
      function, n = 47). There was no difference between diagnostic groups in anal
      sphincter pressures. However, rectal sensitivity to balloon distension was lower
      (P < 0.05) in patients with delayed transit. Paradoxical puborectalis contraction
      (PPC) was found on EMG in 42 patients (31%). The prevalence of PPC was higher (P
      < 0.001) in patients with pelvic-floor dysfunction. Inability to evacuate the
      rectal balloon was reported by 37% of patients with pelvic-floor dysfunction and
      12% of patients with normal pelvic-floor function (P < 0.001). Rectocele was the
      only anatomic abnormality at defecography which was associated with poor rectal
      emptying. CONCLUSIONS: About two-thirds of our patients with constipation had
      objective evidence of delayed transit or pelvic-floor dysfunction. No single test
      could reliably identify any of the pathophysiologic subgroups of constipation.

PMID- 9930391
TI  - Undiagnosed coeliac disease is common in Finnish adults.
AB  - BACKGROUND: Large-scale screening for coeliac disease has suggested that the
      disease is more prevalent than anticipated. In the screening studies published,
      only a minor proportion of those with a positive result have undergone jejunal
      biopsy to confirm the diagnosis. Our aim was to search for previously undiagnosed
      patients with coeliac disease by means of antiendomysium antibodies, which are
      more specific for the disease than serum antigliadin antibodies, and to study
      jejunal histology in each with a positive titre. METHODS: Serum from 1070 adults
      working at Helsinki University Central Hospital were screened for untreated
      coeliac disease with IgA antiendomysium antibodies. All adults with positive
      titres underwent jejunal biopsy for villous structure analysis and counting of
      CD3-positive cells and cells bearing the gamma/delta T-cell receptor. RESULTS:
      Coeliac disease was confirmed in a jejunal biopsy specimen from 8 of the 11
      subjects with positive antiendomysium titres--that is, a frequency of 1 in 130.
      Seven of these eight coeliac patients had had minor abdominal discomfort for
      years, and one patient had a diagnosis of hyperthyroidism. None of the patients
      had osteoporosis, four had low iron storages, but only two were anaemic; no other
      nutritional deficiencies were found. The three other adults had a positive
      antiendomysium titre but a normal villous structure. One of these three was
      regarded as a false-positive case (titre, 1 in 5). The two other subjects
      (titres, 1 in 400) had increased numbers of CD3-positive T cells and gamma/delta
      T-cell receptor-bearing cells, suggesting a predisposition for coeliac disease.
      CONCLUSIONS: Undiagnosed coeliac disease is common in the adult population in
      Finland; in this study the prevalence was 1 in 130. Screening for coeliac disease
      is recommended on minor suspicion.

PMID- 9930392
TI  - Recognition of bactericidal/permeability-increasing protein by perinuclear anti
      neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients:
      prevalence and clinical significance.
AB  - BACKGROUND: The aim of this study was to evaluate a) the role of
      bactericidal/permeability-increasing protein (BPI) as a possible antigen
      determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity
      in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI
      antibodies in patients with ulcerative colitis on the basis of their p-ANCA
      status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of
      indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a
      group of 112 ulcerative colitis patients (including 42 patients subjected to
      proctocolectomy) well defined as far as their clinical features and p-ANCA
      status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated
      patients and were significantly more frequent in p-ANCA-positive patients (32%
      versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI
      antibodies was similar in non-operated and operated patients and was high in men,
      in patients with an extensive and aggressive disease, and in patients developing
      pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a
      neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis
      sera. The presence of anti-BPI antibodies appears to identify further immunologic
      and clinical heterogeneity in ulcerative colitis.

PMID- 9930393
TI  - Effect of psychotherapy on the course of Crohn's disease. Results of the German
      prospective multicenter psychotherapy treatment study on Crohn's disease. German
      Study Group on Psychosocial Intervention in Crohn's Disease.
AB  - BACKGROUND: Our aim was to study the influence of psychotherapy in addition to a
      standardized corticosteroid treatment on the somatic and psychosocial course of
      Crohn's disease. METHODS: In a prospective, randomized multicenter study 108 of
      488 patients received either drug treatment or, in the intervention group,
      additionally psychotherapy in the first half of the 2-year follow-up period.
      RESULTS: Eighty-four patients (77.8%) completed the somatic and 81 (75%) the
      psychosocial follow-up. Twenty-three per cent of the control group and 30% of the
      psychotherapy group showed episode-free courses; 29% and 17%, respectively,
      underwent surgery due to failure of drug treatment. The main analysis, which was
      based on subranking by number, duration, and severity of relapses, failed to show
      significant differences between the two groups (P = 0.125). The same result was
      obtained for the psychosocial status after 1 year in the main target criteria
      depression, anxiety, psychosocio-communicative status, and quality of life.
      CONCLUSIONS: The confirmatory analysis did not prove significantly better courses
      after additional psychotherapy. There was a tendency towards fewer operations.

PMID- 9930394
TI  - The sedimentable sterols in gallstone patients before and during ursodeoxycholic
      acid and simvastatin treatments.
AB  - BACKGROUND: The insoluble material in supersaturated bile is prerequisite for the
      formation of gallstones. We therefore studied the biliary precipitable and
      soluble cholesterol and noncholesterol sterols, including the cholesterol
      precursor sterols (including lanosterol and lathosterols), and the plant sterols
      campesterol and sitosterol, and cholestanol, which usually reflect cholesterol
      synthesis and absorption, respectively, before and after a 6-month treatment with
      ursodeoxycholic acid (UCDA), 15.4 +/- 4 mg/kg/day (standard error of the mean) or
      simvastatin (40 mg/day) in 21 patients with cholesterol gallstones, to obtain
      further information about the factors contributing to the formation of
      gallstones. METHODS: The sediment and supernatant fractions of duodenal bile
      samples were separated by ultracentrifugation and analyzed with gas-liquid
      chromatography. RESULTS: At the base line (n = 21) 50% +/- 3% of biliary
      cholesterol and a variable amount of the noncholesterol sterols (from 14% of
      lanosterol to 62% of cholestanol) were in the sediment fraction. The pattern of
      the noncholesterol sterols in the sediment resembled that of gallstones described
      previously. At base line body mass index was positively related to the percentage
      of precipitable cholesterol in bile (r = 0.46, P < 0.05), and the serum
      sitosterol proportion negatively related to the molar percentage of biliary
      cholesterol and positively to that of bile acids (r = -0.46 and r = 0.50, P <
      0.05 for both). UDCA decreased the precipitable percentage of cholesterol from
      46% to 31% (P < 0.03) and simvastatin from 57% to 42% (P = 0.05). Both drugs also
      decreased the precipitable percentages of lathosterols and cholestanol while
      increasing that of lanosterol. In relation to cholesterol, the sediment to
      supernatant ratios of all methylsterols were increased, whereas those of polar
      lathosterols tended to decrease during UDCA treatment. CONCLUSIONS: Patients with
      high body mass index have more precipitable cholesterol in their bile. Although
      both UDCA and simvastatin decreased the precipitable cholesterol, the bile still
      contained one-third of its cholesterol in the sedimentable form.

PMID- 9930395
TI  - Hemodynamic effects of 8-day DL-028 and octreotide administration in rats with
      portal hypertension.
AB  - BACKGROUND: DL-028 (chemical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]
      2,3-dihydroimidaz o[1,2-c]quinazolin-5(6H)-one (27b)) is a synthetic alpha1
      adrenoceptor antagonist. The present study was undertaken to investigate the
      hemodynamic effects of chronic DL-028 administration, alone or in combination
      with octreotide, in rats with portal hypertension. METHODS: Portal hypertension
      was induced by partial portal-vein ligation. Portal-hypertensive rats were
      allocated to one of the four groups: vehicle group (saline, 0.5 ml/12 h),
      octreotide group (30 microg/kg/12 h), DL-028 group (0.4 mg/kg/12 h), and
      octreotide (30 mg/kg/l2 h) plus DL-028 (0.4 mg/kg/12 h) group, with eight rats in
      each group. DL-028 or saline was administered by gavage and octreotide by
      subcutaneous injection. Drugs were given immediately after ligation and for 8
      consecutive days thereafter. Systemic and splanchnic hemodynamic variables were
      measured thereafter. RESULTS: Portal-vein-ligated rats showed a typical
      hyperdynamic state as compared with sham-operated rats. The portal venous
      pressure, portal tributary blood flow, and cardiac index were significantly
      reduced by treatment with octreotide, DL-028, or octreotide plus DL-028 in portal
      hypertensive rats. Hyperdynamic variables of systemic, renal, hepatocollateral,
      and portal territory vascular resistances and renal and hepatic arterial blood
      flow were ameliorated by treatment with octreotide or octreotide plus DL-028 in
      portal-hypertensive rats. Octreotide plus DL-028 treatment exerted better
      hemodynamic effects on the cardiac index but worse effects on systemic and
      hepatocollateral vascular resistance than octreotide treatment alone. CONCLUSION:
      Although either DL-028 or octreotide ameliorated portal hypertension and
      splanchnic hyperemia in portal-hypertensive rats, octreotide treatment exerted
      more beneficial hemodynamic effects than DL-028 treatment. The combination of
      octreotide and DL-028 conferred no better hemodynamic benefits than octreotide
      alone, except on the cardiac index.

PMID- 9930397
TI  - Small-bowel pandiverticulosis--a potential source of recurrent gastrointestinal
      bleeding. Report of a case and review of the literature.
AB  - Acquired diverticulae of the jejunum and ileum are uncommon and usually
      asymptomatic in most patients. Rarely they may cause intestinal obstruction,
      acute peritonitis due to perforation, or gastrointestinal hemorrhage. In most
      cases only a few diverticulae are present, and owing to their location diagnosis
      is often delayed. We herein report an unusual case of extensive panjejunoileal
      diverticulosis that induced recurrent gastrointestinal bleeding. Although rare,
      this disorder should be considered in the evaluation of obscure gastrointestinal
      bleeding.

PMID- 9930396
TI  - Bombesin-induced pancreatic regeneration in pigs is mediated by p46Shc/p52Shc and
      p42/p44 mitogen-activated protein kinase upregulation.
AB  - BACKGROUND: In several animal species the pancreas has the capacity to partially
      regenerate in a self regulating process. A complex network of growth factors
      modulates this process. There is evidence that bombesin stimulates pancreatic
      regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large
      mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled
      receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce
      the transcriptional upregulation of genes involved in cell proliferation. The
      aims of our study were to determine whether bombesin stimulates pancreatic growth
      in large mammals and whether this event requires Shc-MAP kinase pathway
      upregulation. METHODS: Three groups of pigs were submitted to sham operation
      (group 1); to subtotal (70%) distal pancreatectomy (group 2), and to subtotal
      pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group
      3). After a 4-week follow-up a second laparotomy was performed, and the residual
      pancreas removed. p46Shc, p52Shc and p66Shc, Grb2, and p42/p44 MAP kinase
      expression and phosphorylation were measured either in freshly isolated
      pancreatic acinar cells or whole pancreatic extracts. RESULTS: In vivo bombesin
      administration resulted in: 1) approximately 100% growth of pancreatic duodenal
      lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold
      increase in the rate of pancreatic acinar cell proliferation. Incubating freshly
      isolated pancreatic acinar cells with bombesin resulted in time- and
      concentration-dependent stimulation of p46Shc/p52Shc phosphorylation, Shc-Grb2
      complex formation, and p42/p44 MAP kinase activation. In vivo bombesin
      administration significantly upregulated p46Shc/p52Shc and MAP kinase expression
      and/or activity in whole pancreatic extracts. CONCLUSIONS: In vivo chronic
      bombesin administration stimulates pancreatic regeneration after pancreatectomy
      in large mammals. Bombesin-stimulated pancreatic growth is associated with
      upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.

PMID- 9930398
TI  - Heterozygosity of the haemochromatosis mutation, C282Y, does not influence
      susceptibility to alcoholic cirrhosis.

PMID- 9930399
TI  - Assessment of the arachidonic acid content in foods commonly consumed in the
      American diet.
AB  - Arachidonic acid (AA) is an extremely important fatty acid involved in cell
      regulation. When provided in the diet, it is cogently incorporated in membrane
      phospholipids and enhances eicosanoid biosynthesis in vivo and in vitro; however,
      controversy exists as to the levels of AA in food and in the diet. This study
      determined the amount of AA in cooked and raw portions of beef (rib eye), chicken
      (breast and thigh), eggs, pork (loin), turkey (breast), and tuna; it compared
      these results to values published in Agriculture Handbook No. 8 (HB-8). The
      cooked portions were prepared as described in HB-8. With the exception of chicken
      thigh and tuna, the levels of AA (w/w) in the selected foods analyzed were
      significantly higher, in general, than those values published in HB-8. The
      greatest differences were observed in beef (raw and cooked), turkey breast (raw
      and cooked), and pork (cooked) where AA levels were twice that of the values in
      HB-8. In contrast, the AA and n-3 fatty acid contents in tuna were almost half
      the HB-8 values. The present data indicate that HB-8 tends to underreport the
      amounts of AA in a number of foods commonly consumed in the American diet, and
      new initiatives should be considered to validate and update the current database
      for fatty acid composition of foods.

PMID- 9930400
TI  - Involvement of phospholipids in apolipoprotein B modification during low density
      lipoprotein oxidation.
AB  - An increased amount of phospholipids remained attached on delipidated
      apolipoprotein B originated from oxidized low density lipoprotein (LDL). 31P
      nuclear magnetic resonance analysis of such apolipoprotein showed an organic
      phosphorus peak at -0.55 ppm, which suggests the formation of adducts (most
      probably Schiff bases) of oxidized phospholipids with apolipoprotein B. The above
      reaction occurs in parallel with the hydrolysis of oxidized phospholipids,
      catalyzed by the LDL-attached platelet-activating factor acetylhydrolase, and may
      contribute to the proatherogenic effect of oxidatively modified low density
      lipoprotein.

PMID- 9930401
TI  - Fish oil supplementation with and without added vitamin E differentially
      modulates plasma antioxidant concentrations in healthy women.
AB  - The purpose of this study was to assess the effect of fish oil with or without
      vitamin E on plasma vitamin antioxidants. Thirty-three apparently healthy women
      aged 18-28 yr were recruited from the university environs, and 30 completed the
      double-blinded, parallel design supplementation trial. Blood samples were
      collected at baseline (week 0) and following 28 d of supplementation with three
      capsules/d (0.8 g x 3) of either fish oil (FO) or FO with vitamin E (3 IU/g)
      (FOE). An additional blood sample was taken at day 91 (washout). Plasma
      antioxidant vitamins, fatty acid composition, and lipid peroxides were measured.
      Plasma alpha-tocopherol concentrations were increased significantly in both
      groups postsupplementation FO (P = 0.018) and FOE (P = 0.003) compared with
      baseline and washout values. Plasma retinol concentration was significantly
      increased (P = 0.034) compared with baseline and washout values following
      supplementation with FOE but not FO, while plasma beta-carotene was significantly
      increased (P = 0.036), compared with baseline and washout values, following
      supplementation with FO but not FOE. There was a trend (P = 0.059) toward
      decreased plasma ascorbic acid following FO supplementation compared with
      baseline and washout. Plasma lipid peroxides did not change following either
      supplementation. Results suggest that low-dose FO feeding with and without
      vitamin E differentially modulates plasma antioxidant vitamins but has no
      significant effect on lipid peroxidation.

PMID- 9930402
TI  - Vitamin E reduces cholesterol esterification and uptake of acetylated low density
      lipoprotein in macrophages.
AB  - The effects of vitamin E on cholesteryl ester (CE) metabolism in J774 cells were
      examined. Pretreatment of J774 cells with vitamin E at concentrations above 50
      microM significantly decreased acetylated low density lipoprotein (LDL)-induced
      incorporation of [14C]oleate into CE in cells in a dose-dependent manner. This
      was partly due to vitamin E also significantly inhibiting the uptake of [3H]CE
      labeled acetylated LDL by J774 cells. A trend existed toward suppression of acyl
      CoA:cholesterol acyltransferase (ACAT) activity in the cell lysate at high
      vitamin E concentration, but there was no effect on hydrolysis of CE. These data
      indicate that vitamin E reduces the uptake of modified LDL and suppresses ACAT
      activity, resulting in less cholesterol esterification in macrophages: a novel
      mechanism underlying the antiatherogenic properties of vitamin E.

PMID- 9930403
TI  - Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3
      methylglutaryl-CoA reductase, and low density lipoprotein receptor-related
      protein mRNA expression in healthy humans.
AB  - We investigated the possibility that dietary cholesterol downregulates the
      expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3
      methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo
      in healthy humans. We also studied the variations of the LDL receptor-related
      protein (LRP) gene in the same conditions. Dieters (n = 5) were submitted to a 4
      d fat restriction (mean cholesterol intake: 6+/-4 mg/d), followed by a 7-d
      cholesterol (a mean of 791+/-150 mg/d) supplementation. Controls (n = 3) did not
      change their diet. During fat restriction, serum total and LDL cholesterol
      decreased significantly (P < 0.05), and LDL receptor and HMG-CoA reductase mRNA
      copy numbers in mononuclear cells increased by 57 and 147%, respectively (P <
      0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL
      receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P < 0.05) and LRP
      mRNA increased by 59% (P < 0.005). The changes in LDL receptor and HMG-CoA
      reductase mRNA abundance were correlated (r = +0.79, P = 0.02) during cholesterol
      reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r = 
      0.70, P = 0.05). Also, 70% of the variability in LRP mRNA (P < 0.005) was
      explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular
      cholesterol content, the coordinate feedback repression of genes governing the
      synthesis and uptake of cholesterol, are operating in vivo in humans. However,
      serum cholesterol did not increase in response to dietary cholesterol, suggesting
      that these mechanisms may not play as predominant a role as previously believed
      in the short-term control of serum cholesterol in vivo in humans. A new finding
      is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may
      participate in the control of serum cholesterol. Further in vivo studies in
      humans are warranted to explore the molecular mechanisms of the physiological
      response to dietary cholesterol in humans.

PMID- 9930405
TI  - Regiospecific analysis of fractions of bovine milk fat triacylglycerols with the
      same partition number.
AB  - Bovine milk fat was fractionated using preparative reversed-phase high
      performance liquid chromatography. The conditions consisted of two successive
      linear gradients of acetonitrile and tert-butylmethylether, followed by a final
      isocratic mixture of the two eluants, leading to triacylglycerols grouped by
      their partition number (PN). Fractions corresponding to partition numbers 32 to
      50 were isolated and analyzed for fatty acid distribution between sn-1,3 and sn-2
      positions by Grignard degradation. Results showed that the fatty acid
      distribution in milk fat triacylglycerols is nonrandom. The distribution of short
      chain fatty acids, stearic (predominantly at sn-1,3 position) and palmitic
      (predominantly sn-2 position), did not change with triacylglycerol size. Medium
      chain fatty acids were predominantly located at sn-2 position, but their
      proportion at this position decreased with triacylglycerol size. Oleic acid
      distribution was also size-dependent in that it was located in high proportions
      at sn-2 position in smaller triacylglycerols and vice versa. Results also showed
      that the sn-2 position was more unsaturated than sn-1,3 position in the PN range
      from 32 to 40, but it was more saturated in triacylglycerols with higher PN.

PMID- 9930404
TI  - Effect of diet on the fatty acid and molecular species composition of dog retina
      phospholipids.
AB  - Dogs were born to mothers fed commercial diets low or enriched in n-3 fatty acids
      and raised on those diets until they were about 50 d old. Retinas were removed,
      lipids were extracted, and total phospholipids were analyzed for fatty acid and
      molecular species composition. Animals from the low n-3 group had significantly
      lower retinal levels of 22:6n-3 and higher levels of n-6 fatty acids, especially
      20:4n-6 and 22:5n-6. There was no difference in the retinal levels of 18:2n-6,
      and only small differences were found in saturated and monounsaturated fatty
      acids. The most dramatic differences in molecular species occurred in 22:6n-3
      22:6n-3 (4.7 vs. 0.8%) and 18:0-22:6n-3 (27.6 vs. 14.4%); total molecular species
      containing 22:6n-3 were significantly lower in the low n-3 group (45.5 vs.
      24.0%). Molecular species containing 20:4n-6 and 22:5n-6 were greater in the low
      n-3 animals (13.0 vs. 25.7%), as were molecular species containing only saturated
      and monounsaturated fatty acids (40.8 vs. 35.4%). These results show that modest
      differences in the amount of n-3 fatty acids in the diets of dogs can have
      profound effects on the fatty acid and molecular species composition of their
      retinas.

PMID- 9930406
TI  - Calcium-independent phospholipase A2 in isolated rabbit ventricular myocytes.
AB  - We characterized phospholipase A2 (PLA2) activity in isolated rabbit ventricular
      myocytes with respect to subcellular distribution, substrate specificity, and
      Ca2+ dependency. Membrane-associated PLA2 was found to be an order of magnitude
      greater than cytosolic PLA2. Ventricular myocyte PLA2 activity was enhanced
      following protease-activated receptor stimulation with thrombin and was found to
      be largely Ca2+-independent and selective for phospholipid substrates containing
      arachidonic acid at the sn-2 position. Immunoblot analysis using an antibody to
      cytosolic Ca2+-independent PLA2 from Chinese hamster ovary cells recognized a
      membrane-associated protein with a molecular mass of approximately 80 kDa;
      however, differences in pH optima, response to inhibitors, and substrate
      selectivity of membrane-associated and cytosolic PLA2 activity suggest the
      presence of multiple Ca2+-independent PLA2. Pretreatment with bromoenol lactone,
      a specific inhibitor of Ca2+-independent PLA2, significantly attenuated membrane
      associated and cytosolic PLA2 in unstimulated and thrombin-stimulated myocytes.
      Pretreatment with methyl arachidonyl fluorophosphonate, mepacrine, or dibucaine
      had no significant effect on PLA2 activity under all conditions tested.
      Ventricular myocyte PLA2 activity was significantly inhibited by ATP, GTP, and
      their nonhydrolyzable analogs and was regulated by protein kinase C activity.
      These studies demonstrate the presence of one or more unique membrane-associated
      Ca2+-independent PLA2 in isolated ventricular myocytes that exhibit a preference
      for phospholipids with arachidonate at the sn-2 position and that are activated
      by thrombin stimulation.

PMID- 9930407
TI  - Phytanic acid alpha-hydroxylation by bacterial cytochrome P450.
AB  - Fatty acid alpha-hydroxylase, a cytochrome P450 enzyme, from Sphingomonas
      paucimobilis, utilizes various straight-chain fatty acids as substrates. We
      investigated whether a recombinant fatty acid alpha-hydroxylase is able to
      metabolize phytanic acid, a methyl-branched fatty acid. When phytanic acid was
      incubated with the recombinant enzyme in the presence of H2O2, a reaction product
      was detected by gas chromatography, whereas a reaction product was not detected
      in the absence of H2O2. When a heat-inactivated enzyme was used, a reaction
      product was not detected with any concentration of H2O2. Analysis of the
      methylated product by gas chromatography-mass spectrometry revealed a
      fragmentation pattern of 2-hydroxyphytanic acid methyl ester. By single-ion
      monitoring, the mass ion and the characteristic fragmentation ions of 2
      hydroxyphytanic acid methyl ester were detected at the retention time
      corresponding to the time of the product observed on the gas chromatogram. The Km
      value for phytanic acid was approximately 50 microM, which was similar to that
      for myristic acid, although the calculated Vmax for phytanic acid was about 15
      fold lower than that for myristic acid. These results indicate that a bacterial
      cytochrome P450 is able to oxidize phytanic acid to form 2-hydroxyphytanic acid.

PMID- 9930408
TI  - In vivo studies of the biosynthesis of vernolic acid in the seed of Vernonia
      galamensis.
AB  - In vivo radiotracer experiments using [1-(14C)]acetate as the precursor were
      conducted to investigate the biosynthesis of vernolic acid (12, 13-epoxy-cis-9
      octadecenoic acid) in the seeds of Vernonia galamensis. The acetate precursor
      radioactively labeled vernolate in phosphatidylcholine (PC), diacylglycerol, and
      triacylglycerol. Time-course kinetics of the incorporation of the radioactive
      tracer indicated that vernolate is synthesized while the acyl moiety is
      esterified to PC. Pulse-chase experiments provided additional supporting evidence
      that vernolate is synthesized while esterified to PC. These results are
      consistent with the hypothesis that linoleoyl PC is the precursor of vernoleoyl
      PC. Subsequently, vernolate is quickly moved from the PC pool to the
      triacylglycerol pool, where it accumulates.

PMID- 9930409
TI  - Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin.
AB  - Curcumin (diferuloyl methane) from rhizomes of Curcuma longa L. binds to
      phosphatidylcholine (PC) micelles. The binding of curcumin with PC micelles was
      followed by fluorescence measurements. Curcumin emits at 490 nm with an
      excitation wavelength of 451 nm after binding to PC-mixed micelles stabilized
      with deoxycholate. Curcumin in aqueous solution does not inhibit dioxygenation of
      fatty acids by Lipoxygenase 1 (LOX1). But, when bound to PC micelles, it inhibits
      the oxidation of fatty acids. The present study has shown that 8.6 microM of
      curcumin bound to the PC micelles is required for 50% inhibition of linoleic acid
      peroxidation. Lineweaver-Burk plot analysis has indicated that curcumin is a
      competitive inhibitor of LOX1 with Ki of 1.7 microM for linoleic and 4.3 microM
      for arachidonic acids, respectively. Based on spectroscopic measurements, we
      conclude that the inhibition of LOX1 activity by curcumin can be due to binding
      to active center iron and curcumin after binding to the PC micelles acts as an
      inhibitor of LOX1.

PMID- 9930410
TI  - Lysophosphatidylcholine acyltransferase activity in Saccharomyces cerevisiae:
      regulation by a high-affinity Zn2+ binding site.
AB  - Saccharomyces cerevisiae cells were demonstrated to contain
      lysophosphatidylcholine (lysoPtdCho) acyltransferase (E.C. 2.3.1.23) activity.
      The enzyme displayed Km(app) of 69 microM for lysoPtdCho and 152 microM for
      oleoyl CoA. Enzyme activity was not affected by the addition of 1 mM Mg2+, Mn2+,
      Ca2+, or 200 mM EDTA. However, Zn2+ inhibited lysoPtdCho acyltransferase activity
      to 33% control values at 0.1 mM and to 7% at 1.0 mM Zn2+. To further explore the
      possibility that lysoPtdCho acyltransferase may contain a high-affinity Zn2+
      binding site, we tested the strong Zn2+ chelator o-phenanthroline for its ability
      to inhibit enzyme activity. LysoPtdCho acyltransferase activity was inhibited to
      18 and 27%, respectively, those of control values in the presence of 2 and 1 mM o
      phenanthroline, implying that a high-affinity Zn2+ binding site exists in
      lysoPtdCho acyltransferase or in an accessory protein that is essential for
      protein stability and/or activity. Saccharomyces cerevisiae lysoPtdCho
      acyltransferase activity displayed a broad lysoPtdCho fatty acyl chain substrate
      specificity utilizing lysoPtdCho molecules ranging in length from C10-C20 (the
      entire range tested). In addition, the enzyme was capable of using the ether
      linked analog of lysoPtdCho, 1-O-alkyl-2-hydroxy-sn-3-glycerophosphocholine, as a
      substrate. The ability of S. cerevisiae to incorporate radiolabeled 1-O-alkyl-2
      hydroxy-sn-3-glycerophosphocholine into phosphatidylcholine in vitro was
      exploited to demonstrate a direct precursor-product relationship between
      lysoPtdCho molecules and their incorporation into phosphatidylcholine in vivo.
      Identical labeling results were obtained in S. cerevisiae cells disrupted for
      their major transacylase activity, PLB1, demonstrating that the incorporation of
      lysolipid was via acyltransferase, and not transacylase, activity.

PMID- 9930412
TI  - Twenty-year follow-up of the Hancock modified orifice porcine aortic valve.
AB  - BACKGROUND: The entire experience with the Hancock modified orifice porcine
      bioprosthetic aortic valve from 1976 to 1996 at the Brigham and Women's Hospital
      has been reviewed. Eight hundred forty-three patients received this valve with a
      total follow-up of 61,114 months, and a mean follow-up of approximately 72.5
      months. There were 490 men and 353 women, and the predominate lesion was aortic
      stenosis (636 of 843); 365 (43%) patients required a concomitant coronary artery
      bypass graft operation. METHODS: Patients were followed prospectively in the
      Brigham Cardiac Valve Data Registry, and the data were analyzed by the SAS
      statistical package, using actuarial survival curves and incidence per patient
      year of morbidity and mortality. RESULTS: The overall operative mortality was 45
      of 843 (5.3%) with 23 of 478 (4.8%) for isolated aortic valve replacement and 22
      of 365 (6.0%) for aortic valve plus coronary artery bypass graft operation. The
      major morbidity of this valve was structural valve dysfunction, which was
      significantly related to the age of the patient in whom the valve was placed.
      Actuarial probability of freedom from structural valve degeneration at 5, 10, and
      15 years overall was 99%+/-1%, 79%+/-3% and 57%+/-4%, at 15 years, respectively.
      In patients younger than 50 years, freedom from structural valve dysfunction was
      16%+/-8%, whereas in the age group older than 70 years it was 87%+/-5% (p =
      0.0005). Thromboembolism at 10 and 15 years was 81%+/-3% overall, 84%+/-2% in
      patients in normal sinus rhythm, and 57%+/-13% in patients with chronic atrial
      fibrillation. CONCLUSIONS: The Hancock modified orifice aortic valve, despite its
      more complicated fabrication, has been a reliable porcine bioprosthetic valve and
      can be used reliably in patients older than 70 years because of its low
      structural valve degeneration rate, and protection from stroke and anticoagulant
      hemorrhage in those patients in sinus rhythm.

PMID- 9930411
TI  - Chemiluminescent determination of cholesterol hydroperoxides in human erythrocyte
      membrane.
AB  - A method for separating, detecting, and quantifying cholesterol hydroperoxide (Ch
      OOH) based on extraction, purification by solid-phase extraction cartridge, high
      performance liquid chromatography with chemiluminescent detection (HPLC-CL), and
      liquid chromatography-mass spectrometry has been developed for human erythrocyte
      membrane. We prepared standard compounds of the cholesterol 5alpha-, 7alpha-, and
      7beta-hydroperoxides (Ch 5alpha-OOH, Ch 7alpha-OOH, and Ch 7beta-OOH). An octyl
      silica column with methanol/water/acetonitrile 89:9:2 (by vol) as eluent was used
      to determine Ch-OOH. HPLC-CL that incorporated cytochrome c and luminol as the
      post-column luminescent reagent was used. We also investigated the optimal assay
      conditions and how to prevent formation of artifact Ch-OOH. Analysis of
      erythrocyte membranes from seven healthy volunteers identified Ch 7alpha-OOH and
      Ch 7beta-OOH, but not Ch 5alpha-OOH, as commonly occurring components. The
      respective mean concentrations of Ch 7alpha-OOH and Ch 7beta-OOH were 2.5+/-1.6
      and 5.4+/-3.5 pmol/mL blood.

PMID- 9930413
TI  - A 20-year experience with the Hancock porcine xenograft in the elderly.
AB  - BACKGROUND: The availability of 20 years of follow-up data on the Hancock porcine
      valve (Medtronic Inc, Irvine, CA) allows determination of long-term actual and
      actuarial failure rates in the elderly. METHODS: We analyzed outcomes after
      mitral or aortic valve replacement with the Hancock porcine valve in 491
      consecutive patients, comparing actual and actuarial valve failure rates in the
      elderly (age 65 or older) with those in younger patients. RESULTS: The average
      age of aortic valve replacement recipients was 68+/-14 years (N = 243) and of
      mitral valve replacement recipients, 64+/-12 years (N = 248). Average follow-up
      was 7.0 years (1,673 patient-years) for aortic valve replacement and 7.3 years
      (1,781 patient years) for mitral valve replacement recipients. The median time to
      reoperation or structural failure was 15.9 years for aortic valve replacement
      patients and 14.3 years for mitral valve replacement patients. However, few
      elderly patients survived to 15 years (22% of the elderly aortic valve
      replacement and 13% of the older mitral valve replacement patients). The 15-year
      actual reoperation rate was therefore only 10% in the elderly aortic valve
      replacement compared to 30% in the younger aortic valve replacement patients. For
      mitral valve replacement, the 15-year actual reoperation rate was 11% in the
      elderly and 36% in the younger patients. The lifetime reoperation risk (the
      maximum potential number of patients who might ever undergo reoperation during
      their lifetime) is the sum of actual survival and actual reoperation rates. The
      lifetime reoperation risk was 20% or less for elderly aortic valve replacement
      patients and 18% or less for elderly mitral valve replacement patients.
      CONCLUSION: These data suggest that about 1 in 10 elderly patients (65 years or
      older) receiving a Hancock valve will require reoperation within 15 years and
      less than one in five will ever require reoperation in their lifetimes.

PMID- 9930414
TI  - Carpentier-Edwards standard porcine bioprosthesis: a 21-year experience.
AB  - BACKGROUND: The Carpentier-Edwards standard porcine bioprosthesis experience to
      21 years has been evaluated to determine the influence of structural valve
      deterioration by valve position in various age groupings. METHODS: From 1975 to
      1988, 1,181 patients had the prosthesis implanted in 1,198 procedures. The mean
      age of the population was 57.9+/-12.5 years (range, 21 to 85 years). Aortic valve
      replacement was performed in 564 patients (47.8%); mitral valve replacement, 478
      (40.5%); and multiple valve replacement, 132 (11.2%). Concomitant procedures were
      performed in 337 patients (28.5%), and 140 (11.9%) had previous operations.
      RESULTS: The early mortality was 8.1% (97), only 0.4% (5) of which were valve
      related. The total follow-up was 10,405 years (mean, 8.8+/-5.2 years). The late
      mortality was 5.7%/patient-year (591), with the valve-related component
      1.6%/patient-year (168) with a 13% reoperative mortality (56). The linearized
      rate of structural valve deterioration was 3.8%/patient-year (395), with overall
      complications of 7.1%/patient-year (737). The overall survival at 20 years was
      17.2%+/-3.1% (p < 0.05; aortic valve replacement greater than mitral valve
      replacement or multiple valve replacement). The freedom from structural valve
      deterioration was, at 18 years, 25.8%+/-2.8% overall, AVR 40.6%+/-4.2%, and MVR
      8.5%+/-3.4% (p < 0.05, aortic valve replacement greater than mitral valve
      replacement or multiple valve replacement). The freedom from structural valve
      deterioration for aortic valve replacement was, at 15 years, for patients older
      than 70 years, 82.9%+/-9.1%; 61 to 70 years, 73.2%+/-4.7%; 51 to 60 years,
      58.8%+/-5.4%; 41 to 50 years, 41.7%+/-8.2%; and 21 to 40 years, 25.5%+/-7.8%. The
      freedom from structural valve deterioration for mitral valve replacement was, at
      15 years, for patients older than 70 years, 89.8%+/-7.6%; 61 to 70 years, 22.8%+/
      6.3%; 51 to 60 years, 26.3% +/- 5.7%; 41 to 50 years, 11.7%+/-5.6%; and 21 to 40
      years, 7.0%+/-4.7%. CONCLUSIONS: The prosthesis is recommended for aortic valve
      replacement for patients older than 70 years and for patients 61 to 70 years
      (when extended longevity is not anticipated) and for mitral valve replacement for
      patients older than 70 years.

PMID- 9930415
TI  - Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine
      valves.
AB  - BACKGROUND: The determinants of long-term outcome 15 years or more after porcine
      valve replacement are poorly documented. METHODS: A retrospective review was
      performed of patients undergoing valve replacement with standard Carpentier
      Edwards aortic (n = 531), mitral (n = 492), and tricuspid (n = 96) valves.
      RESULTS: Patient survival was 26%+/-3%, 23%+/-2%, and 31%+/-8% 15 years after
      aortic, mitral, and tricuspid valve replacements, respectively. Independent
      determinants of impaired long-term survival for aortic or mitral valve
      replacement were multiple valve replacement, older age, renal disease, lung
      disease, or coronary disease. Actual (versus actuarial) freedom from reoperation
      at 15 years was 86%+/-2%, 76%+/-2%, and 95%+/-2% after aortic, mitral, and
      tricuspid valve replacement, respectively. Risk factors for reoperation were
      young age for aortic or mitral valve replacement, previous operation for aortic
      valve replacement, and large valve size for mitral valve replacement. Freedom
      from thromboembolism was 77%+/-4%, 62%+/-9%, and 80%+/-5%; from hemorrhage, 95%+/
      5%, 87%+/-4%, and 82%+/-6%; and from endocarditis, 94%+/-1%, 96%+/-1%, and 89%+/
      5% 15 years after aortic, mitral, and tricuspid valve replacement, respectively.
      Risk factors for thromboembolism or hemorrhage were multiple valve replacement
      and age. CONCLUSIONS: The standard Carpentier-Edwards bioprosthesis continues to
      provide relatively low complication rates at 15 years, especially in the aortic
      and tricuspid positions, and especially in patients older than 60 years or with
      significant comorbdity.

PMID- 9930416
TI  - Carpentier-Edwards supraannular porcine bioprosthesis evaluation over 15 years.
AB  - BACKGROUND: The Carpentier-Edwards supraannular porcine bioprosthesis experience
      during 15 years has been evaluated to determine the incidence of structural valve
      deterioration by valve position in various age groupings. METHODS: From 1981 to
      1995, 2,943 patients older than 20 years had the prosthesis implanted in 3,024
      procedures. The mean age of the population was 65.5+/-11.9 years (range, 21 to 89
      years). Aortic valve replacement was performed in 1,657 patients (54.8%); mitral
      valve replacement, 1,092 (36.1%); multiple valve replacement, 253 (8.3%);
      pulmonary valve replacement, 2 (0.1%); and tricuspid valve replacement, 20
      (0.7%). Concomitant procedures were performed in 1,332 patients (45.3%), and 352
      (12.0%) had previous procedures. RESULTS: The early mortality was 8.9% (270),
      only 0.4% (11) valve-related. The total follow-up was 17,471 years (mean, 5.9+/
      4.1 years). The late mortality was 5.2%/ patient-year (901) with the valve
      related component 1.0%/patient-year (171). The reoperation rate was 2.1%/ patient
      year (369) with 4.3% mortality (16). The linearized rate of structural valve
      deterioration was 2.0%/patient-year (341), and overall complications,
      5.9%/patient-year (1,019). The overall survival, at 15 years, was 31.1%+/2.8% (p
      < 0.05; aortic valve replacement greater than mitral valve replacement or
      multiple valve replacement). The freedom from structural valve deterioration for
      aortic valve replacement was, at 12 years, for patients older than 70 years,
      95.3%+/-2.7%; 61 to 70 years, 92.9%+/-2.1%; 51 to 60 years, 70.1%+/-5.3%; 41 to
      50 years, 60.0%+/-8.8%; and 21 to 40 years, 75.7%+/-7.3%. The freedom from
      structural valve deterioration for mitral valve replacement was, at 12 years, for
      patients older than 70 years, 66.1%+/-9.7%; 61 to 70 years, 53.1%+/-4.7%; 51 to
      60 years, 52.6%+/-5.5%; 41 to 50 years, 39.3%+/-6.9%; and 21 to 40 years, 42.1%+/
      9.4%. CONCLUSIONS: The prosthesis is recommended for aortic valve replacement for
      patients older than 70 years and for patients 61 to 70 years (when extended
      longevity is not anticipated) and for mitral valve replacement for patients older
      than 70 years (when extended longevity is not anticipated).

PMID- 9930417
TI  - Mitroflow pericardial bioprosthesis experience in aortic valve replacement > or
      =60 years of age.
AB  - BACKGROUND: The Mitroflow pericardial bioprosthesis (model 11), a second
      generation pericardial prosthesis, has clinical performance assessment to 10
      years. The authors previously recommended the prosthesis for aortic valve
      replacement in patients 70 years or older. The purpose of the current assessment
      is to report on performance in patients 60 years or older undergoing aortic valve
      replacement. METHODS: This bioprosthesis was implanted in 161 patients (mean age,
      69.5+/-6.3 years; range, 60 to 94 years) with aortic valve replacement from 1982
      to 1992. There were 84 patients 60 to 69 years (mean, 64.5+/-3.1 years) and 77
      patients 70 years or older (mean, 74.8+/-4.3 years). Of the total population,
      concomitant procedures were performed in 63 patients (39.1%); of these, coronary
      artery bypass grafting was performed in 39 (24.2%). RESULTS: The early mortality
      was 4.8% (4 patients) for the 60 to 69-year age group and 10.4% (8) for those 70
      years or older (not significant). The late mortality was 4.4%/patient-year (27)
      for those 60 to 69 years and 6.9%/ patient-year (35) for those 70 years or older
      (not significant). The patient survival for those 60 to 69 years was 58.0%+/-6.3%
      and for those 70 years or older, 45.3%+/-5.9% at 10 years (p < 0.05). The valve
      related mortality for those 60 to 69 years was 0.82%/patient-year (5) and for
      those 70 years or older, 1.58%/patient-year (8) (not significant). The
      reoperation rate for those 60 to 69 years was 3.29%/patient-year (20) and for
      those 70 years or older, 1.0%/patient-year (5) (p < 0.05). The structural valve
      deterioration rate for those 60 to 69 years was 3.13%/ patient-year (19) and for
      those 70 years or older, 1.2%/ patient-year (6) (p < 0.05). CONCLUSIONS: The
      Mitroflow pericardial bioprosthesis remains recommended for aortic valve
      replacement in patients 70 years and older.

PMID- 9930418
TI  - 15-year experience with the Carpentier-Edwards pericardial bioprosthesis.
AB  - BACKGROUND: The aim of the study was to evaluate the late results of the
      Carpentier-Edwards pericardial bioprosthesis, which we have been implanting since
      1981. METHODS: The 812 patients who underwent heart valve replacement with a
      Carpentier-Edwards pericardial bioprosthesis between 1981 and 1996 were reviewed.
      Their clinical, operative, and follow-up data were prospectively recorded in a
      computerized database. All but 29 patients were available for follow-up (96%
      completeness), which averaged 58 months and totaled 3,000 patient-years. RESULTS:
      There were 598 aortic valve replacements (74%), 149 mitral valve replacements
      (18%), and 65 double valve replacements (8%). The mean age at the time of surgery
      was 65 years (range, 18 to 88 years), with 24% of the patients under the age of
      60 years. Preoperatively, 558 patients (69%) were in New York Heart Association
      functional class III or IV. Associated surgical procedures included coronary
      artery bypass grafting in 219 patients (27%) and tricuspid or mitral valve repair
      in 40 (5%). Previous cardiac operations had been performed in 149 patients,
      including 134 valve-related procedures. There were 49 early deaths overall (6%):
      29 after aortic valve replacement (4.8%), 11 after mitral valve replacement
      (7.4%), and 9 with double valve replacement (13.8%). There were 120 late deaths
      for a 10-year actuarial survival rates of 69%+/-3%, 58%+/-7%, and 38%+/-10% for
      aortic, mitral, and double valve replacement, respectively. The 14-year survival
      rate for aortic valve replacement patients is 68%+/-3%. The 10-year and 14-year
      actuarial freedom rates from events after aortic valve replacement are 92% +/-2%
      and 88%+/-4% for thromboembolism, 96%+/-1% and 92%+/-4 for endocarditis, 91%+/-2
      and 72%+/-6% for reoperation, and 93%+/-2% and 80%+/-5% for structural
      dysfunction of the valve. The 10-year actuarial freedom rates from events after
      mitral and double valve replacement are 93%+/-3% and 89%+/-4% for
      thromboembolism, 95%+/-3% and 88%+/-5% for endocarditis, 76%+/-7% and 70%+/-14%
      for reoperation, and 81%+/-7% and 72%+/-15% for structural dysfunction. No
      primary tissue failure of the prosthesis in any position was observed in the 357
      patients aged 70 years or more at the time of valve implantation. CONCLUSIONS:
      The Carpentier-Edwards pericardial valve offers excellent clinical results and
      durability, particularly in the aortic position and for patients older than 70
      years of age.

PMID- 9930419
TI  - Prosthetic replacement of the tricuspid valve: biological or mechanical?
AB  - BACKGROUND: Incidence of tricuspid prosthesis replacement was 1.9% of all
      valvular operations performed between June 6, 1966 and April 18, 1996. Many
      series report similar figures, but institutional experience is limited and the
      consensus on treatment modalities is lacking. METHODS: One hundred tricuspid
      operations were performed on 83 patients (46 female). A primary operation was
      performed in 64 cases, 13 patients had one previous operation, 4 patients had two
      previous operations, and 2 patients had three previous operations. Seventeen
      patients required a tricuspid prosthetic valve rereplacement. There were 2
      emergent and 17 urgent operations. The New York Heart Association class was IV in
      13 patients (mean pulmonary artery pressure, 41 mm Hg), III in 66 patients (mean
      pressure, 38 mm Hg), and II in 21 patients. The most frequent operation was
      simultaneous replacement of the mitral and tricuspid valve (41 patients). Seventy
      biological and 30 mechanical prostheses were used. Total follow-up time was 613
      years, mean 7.4 years (median 4.2 years), with a maximum of 27.8 years, and was
      92% complete. RESULTS: Operative mortality was 24%. Survival was 0.54 (0.48 to
      0.59, n = 39) at 5 years, 0.38 (0.32 to 0.44, n = 27) at 10 years, 0.31 (0.25 to
      0.36, n = 19) at 15 years, 0.29 (0.23 to 0.34, n = 11) at 20 years, and 0.17
      (0.098 to 0.26, n = 3) at 25 years. Early mortality was increased from higher New
      York Heart Association class (hazard ratio = 2.2), congenital disease (hazard
      ratio = 6.9), and valvuloplasty failure (hazard ratio = 4.3). The constant risk
      phase (4%/patient-year) after 2 years was enhanced by older operative age (hazard
      ratio = 1.4). Prosthetic type had no independent effect. Biological prostheses
      were at risk for 300 years and had a reoperation incidence of 4.7%/ patient-year
      (14 events); mechanical prosthesis were at risk for 137 years with a rate of
      2.2%/patient-year (3 events) (p = 0.21). Three valve thromboses were observed in
      old-design mechanical prosthesis. Bioprosthetic degeneration showed a steeper
      rate after 7 years. CONCLUSIONS: This study does not show a clear superiority of
      biological versus mechanical prostheses. In the long run survival with mechanical
      prostheses could be superior, given the high rate of bioprosthetic degeneration
      after 7 years.

PMID- 9930420
TI  - Bioprosthetic replacement after bioprosthesis failure: a hazardous choice?
AB  - BACKGROUND: Following bioprosthetic failure, replacement is usually done with
      mechanical valves to avoid repeated reoperations. METHODS: From 1986 to 1996 we
      operated on 130 patients with bioprosthetic failure, implanting a new
      bioprosthesis; this group included patients with contraindication to
      anticoagulation, tricuspid replacement, and specific patient requests. Mean age
      was 63+/-8 years. RESULTS: The perioperative mortality was 13.8%. At 10 year
      follow-up the actuarial estimate of survival was 77.4%+/-6.6%. Freedom from
      structural valve deterioration was estimated at 81.8%+/-6.3%. Freedom from a
      third operation was estimated at 85.5%+/-5.2%. No patient was permanently
      anticoagulated. Freedom from thromboembolism was estimated at 91.5%+/-4%, and
      there were no hemorrhages. Freedom from cardiac-related deaths was estimated at
      85.7%+/-5%. CONCLUSIONS: This group of patients received the first valve between
      1976 and 1986; the range of the cumulative follow-up reaches 20 years, and the
      extended survival compares favorably with survival of mechanical valves.

PMID- 9930422
TI  - Aortic valve replacement in the elderly: bioprosthesis or mechanical valve?
AB  - BACKGROUND: With increased life expectancy, valve operations are more and more
      common in elderly patients. The choice of valve substitute-mechanical valve or
      bioprosthesis-remains debated. METHODS: Two groups of patients of the same age
      (69, 70, and 71 years) with isolated aortic valve replacement (mechanical 240,
      bioprostheses 289) were compared for mortality, morbidity, and valve-related
      complications. RESULTS: No significant difference was found in survival, valve
      related mortality, valve endocarditis, and thromboembolism. Mechanical valve had
      more bleeding events; bioprostheses had more structural deterioration,
      reoperation, and valve-related morbidity and mortality. CONCLUSIONS: To avoid
      reoperations in octogenarians, the 10-year durability of current bioprostheses
      should be matched with the life expectancy of the particular patient.
      Bioprostheses should be used after 74 years in men and 78 years in women.

PMID- 9930421
TI  - Long-term results of the Carpentier-Edwards pericardial aortic valve: a 12-year
      follow-up.
AB  - BACKGROUND: Pericardial valves have excellent hemodynamic function; however, long
      term durability is questionable. To determine the function of the Carpentier
      Edwards pericardial valve in the aortic position, the results of 310 aortic valve
      replacements performed between 1982 and 1985 were analyzed. Mean age was 64.2+/
      10.8 years (range, 22 to 95 years); 190 (61.3%) were men. Isolated valve
      replacement was performed in 135 patients (43.5%). There were 18 hospital deaths
      (5.8%), none of them valve related. METHODS: Follow-up of 292 survivors was 100%
      complete at a mean of 8.8 years; 2,556 patient-years of follow-up were analyzed.
      There were 150 late deaths (51.4%). Survival at 5, 10, and 12 years were 83%+/
      2%, 47%+/-3%, and 34%+/-3%, respectively. The 12-year actuarial and actual
      freedom from thromboembolism was 87%+/-2% and 89%+/-2%, respectively. Freedom
      from hemorrhage was 91%+/-2% and 92%+/-2%; freedom from endocarditis was 93%+/-2%
      and 95% +/- 1%; and freedom from structural deterioration was 82%+/-4% and 91%+/
      2%, respectively. RESULTS: Actuarial freedom from structural deterioration at 12
      years was considerably higher for 153 hospital survivors 65 years or older, 93%
      (5 explants) compared to 76% (19 explants) for patients younger than 65 years, p
      = 0.03. Of 24 explanted valves for structural deterioration, leaflet
      calcification resulting in stenosis occurred in 20 (83%) and 4 were wear-related
      leaflet tears. CONCLUSIONS: We conclude that the Carpentier-Edwards pericardial
      valve has a low incidence of valve-related complications, that structural
      deterioration is infrequent and results from leaflet calcification, and that the
      low incidence of structural deterioration in patients 65 years or older makes
      this an increasingly appropriate option in this age group.

PMID- 9930424
TI  - Multivariate analysis of survival after malfunctioning biological and mechanical
      prosthesis replacement.
AB  - BACKGROUND: Results of valvular reoperations depend on extrinsic and patients'
      intrinsic risk factors. New prosthetic substitutes continue to appear and the
      clinical effect is difficult to evaluate. Randomized studies are limited by
      patient selection and follow-up time. We followed the patient-centric outcome
      research applied to a large database of valvular operations. METHODS: Between
      January 1, 1970 and January 1, 1995 755 patients underwent one reoperation, 96 a
      second reoperation, and 12 a third reoperation. On January 1, 1996 a common
      closing date follow-up was obtained in 98.7% of reoperated patients.
      Multivariable analysis in the hazard domain was applied to obtain an upgradable
      model of survival that could be used for predictions and treatment comparison.
      RESULTS: Postoperative death hazard showed an early phase merging within 6 months
      with a constant low hazard phase. The survival proportion was 0.65 (70% CL, 0.63
      to 0.67) at 5 years, 0.51 (70% CL, 0.49 to 0.53) at 10 years, 0.47 (range, 0.44
      to 0.49) at 15 years, 0.42 (70% CL, 0.39 to 0.46) at 20 and 25 years. Significant
      incremental risk factors for early mortality were reoperative era 1970 to 1980
      (hazard ratio = 2.8), reoperation number (hazard ratio = 1.9), heart penetration
      on surgery (hazard ratio = 7.6), emergent operation (hazard ratio = 5.8), urgent
      operation (hazard ratio = 2.1), prosthetic thrombosis (hazard ratio = 2.4), acute
      prosthetic endocarditis (hazard ratio = 3.0), acute endocarditis of the natural
      valve at antecedent operation (hazard ratio = 3.2), original floppy valve
      pathology (hazard ratio = 3.2), and mitroaortic replacement (hazard ratio = 5.7).
      Isolated mitral reoperation had a lower risk (hazard ratio = 0.5). Significant
      incremental risk factors for constant phase were: operative era (1970 to 1980)
      (hazard ratio = 2.0), congestive heart failure (hazard ratio = 2.6), reoperation
      on tricuspid valve after previous mitral insertion (hazard ratio = 4.9),
      reoperation for recurring dehiscence (hazard ratio = 4.6), double-valve procedure
      (hazard ratio = 1.6), coronary artery bypass graft (hazard ratio = 2.7), aortic
      root disease at original operation (hazard ratio = 2.1), older operative age
      (hazard ratio = 1.1). Use of bileaflet prosthesis was found to decrease
      significantly (p = 0.0002) the death risk (hazard ratio = 0.2). CONCLUSIONS:
      There is no late uprising hazard, and surviving patients remain exposed to a low
      risk of death (4% of patients per year). Considering simultaneously the
      confounding from operative age and operative era and the many concomitant risk
      factors, survival appears favorably influenced by use of bileaflet valves on
      reoperation.

PMID- 9930423
TI  - Valve-related complications in elderly patients with biological and mechanical
      aortic valves.
AB  - BACKGROUND: Controversy still exists about the choice of aortic prosthesis in
      elderly patients. This study investigates valve- and anticoagulant-related
      morbidity and mortality in elderly patients after aortic valve replacement (AVR)
      with a biologic (BP) or mechanical prosthesis (MP). METHODS: Between 1981 and
      1995, 355 consecutive patients aged 70 years or older (mean, 74+/-4 years; range,
      70 to 87 years) underwent isolated AVR. There were 222 (63%) replacements with an
      MP and 133 (37%) with a BP. Mean follow-up was 3.7+/-2.8 years (range, 3 months
      to 15 years), with a total follow-up of 1,214 patient-years. RESULTS: Hospital
      mortality was 7.6% (27 of 355), decreasing to 4.6% in the last 3 years. There
      were 55 late deaths, 33 in patients with MP and 22 in those with BP. At 10 years
      there was no significant difference between MP and BP recipients in the actuarial
      estimates of survival (51%+/-8% versus 33%+/-13%), freedom from valve-related
      death (82%+/-7% versus 72%+/-12%), and freedom from thromboembolism (84%+/-7%
      versus 94%+/-3%). In contrast, 10-year freedom from anticoagulant-related
      hemorrhages was 74%+/-8% for MP and 99%+/-1% for BP (p = 0.02). Only 1 structural
      deterioration occurred, in a patient with BP. CONCLUSIONS: Satisfactory early
      results can be obtained in elderly patients after AVR with both MP and BP. The
      comparable low late survival in the two groups was predominantly influenced by
      non-valve-related deaths. A higher incidence of anticoagulant-related hemorrhages
      limits the use of MP in elderly patients. Thus, in this population, BP should be
      preferred not just on the basis of their expected longer durability, but mainly
      to avoid the risk of anticoagulant-related hemorrhages.

PMID- 9930425
TI  - The Hancock II bioprosthesis at 12 years.
AB  - BACKGROUND: The Hancock II bioprosthesis has been used for heart valve
      replacement since 1982 in our institution. We previously reported its clinical
      performance at 8 years and at 10 years. This is a progress report on its
      performance at 12 years. METHODS: From 1982 to 1994 the Hancock II bioprosthesis
      was used for aortic valve replacement (AVR) in 723 patients and for mitral valve
      replacement (MVR) in 328 patients. The mean age of the patients was 65 years for
      both groups. Coronary artery disease was present in 42% of patients who had AVR
      and 45% of patients who had MVR. Patients have been followed up prospectively at
      annual intervals; the mean follow-up was 68+/-40 months for AVR and 66+/-43
      months for MVR; it was 99% complete. RESULTS: There were 36 (5%) operative and
      159 late deaths in the AVR group, and 26 (8%) operative and 92 late deaths in the
      MVR. The actuarial survival at 12 years was 54%+/-4% for AVR and 42%+/-5% for
      MVR. Age greater than 65 years and coronary artery disease had a profound effect
      on late survival. At 12 years the freedom from thromboembolism was 86%+/-2% for
      AVR and 90% +/-2% for MVR; from endocarditis, 95%+/-1% for both groups; from
      primary tissue failure, 94%+/-2% for AVR and 82%+/-5% for MVR; and from valve
      reoperation, 89% +/-3% for AVR and 78%+/-5% for MVR. There was no primary tissue
      failure at 12 years in patients older than 65 years who had AVR. CONCLUSIONS: The
      clinical performance of the Hancock II has been very satisfactory and this
      bioprosthesis appears to be more durable than its predecessors.

PMID- 9930426
TI  - Hancock versus stentless bioprosthesis for aortic valve replacement in patients
      older than 75 years.
AB  - BACKGROUND: Stented aortic bioprostheses are routinely used in elderly patients.
      The stent, however, is obstructive and implies several hazards. Stentless aortic
      valves appear to be hemodynamically advantageous. However, their implantation is
      longer and technically more demanding, and durability is still under
      investigation. METHODS: Between January 1993 and December 1996, 77 patients (28
      men) were prospectively randomized to undergo aortic valve replacement using the
      Hancock valves (group A: 40 patients, 16 men; age, 77+/-3 years; body surface
      area, 1.7+/-0.17 m2) or a stentless bioprostheses (group B: 37 patients, 12 men;
      age, 76+/-2 years; body surface area, 1.7+/-0.15 m2; Biocor, 17; Toronto SPV,
      20). Preoperative variables were not significantly different between the two
      groups. Bypass time was 123+/-46 versus 133+/-51 minutes, and aortic cross-clamp
      time was 83+/-26 versus 95+/-24 minutes for group A and group B, respectively
      (not significant). Seven patients in group A (17.5%) and 5 in group B (13.5%) had
      enlargement of the aortic annulus. Valve size normalized to body surface area was
      13.7+/-1.5 versus 14.1+/-1.6 mm/m2 for group A and group B, respectively (not
      significant). Eleven patients in group A (27.5%) and 5 in group B (13.5%) had
      concomitant myocardial revascularization. RESULTS: Overall perioperative
      mortality was 5% in group A (low cardiac output in 2 patients), and 8% in group B
      (low cardiac output in 1; major neurologic event in 2). Follow-up is 97% complete
      (group A, 14.5+/-10 months; group B, 18.5+/-12 months). One patient in group B
      died at 28 months of myocardial infarction. Actuarial survival at 12 and 24
      months is 92% versus 91% and 92% versus 81% for group A and group B,
      respectively. At 6 months, patients in group A showed a peak transaortic gradient
      of 25+/-7 versus 20+/-9 mm Hg in group B. Progressive regression of left
      ventricular mass expressed as a percentage of preoperative value was 10.5% and
      19% for group A and group B at 1 year postoperatively (not significant).
      CONCLUSIONS: Stentless valves represent a valuable alternative to conventional
      prostheses in patients older than 75 years, although no great advantages with
      their use emerge from this study. Continued evaluation particularly with regard
      to evidence of left ventricular remodeling and valve degeneration in the long
      term is warranted.

PMID- 9930427
TI  - Reoperation on stentless aortic xenografts.
AB  - BACKGROUND: Stentless xenografts have been proposed as substitutes for the
      diseased aortic valve. Cases of valve failure requiring reoperation have thus far
      been sporadic. To establish the prevalence and outcome of reoperation on
      stentless aortic xenograft valves, all patients operated on between October 1992
      and October 1996 were reviewed. METHODS: One hundred ninety-nine patients, 94 men
      and 105 women aged 70+/-7 years, had stentless aortic valve replacement for
      aortic stenosis (in 139), insufficiency (19), or both (38). Three prostheses were
      used, including the Biocor PSB (Belo Horizonte, Brazil) (106), Toronto SPV (St.
      Jude Medical, Inc., St. Paul, MN) (52), and O'Brien-Angell (Cryolife, Atlanta,
      GA) (41). While the Biocor PSB and Toronto SPV prostheses are designed to be
      implanted freehand with inflow and outflow suture lines, the O'Brien-Angell valve
      requires a single suture line. RESULTS: There were 7 (3.5%) total and 6 (3%)
      valve-related reoperative procedures during a follow-up extending up to 4 years
      (mean 26+/-20 months). All but one valve-related reoperation, due to endocarditis
      36 months after implant, were early (less than 12 months after initial
      operation). Prevalence of valve-related reinterventions was 1%, 0%, and 12%, and
      freedom from reoperation at 3 years was 98%+/-2%, 100%, and 81%+/-8%, in patients
      receiving the Biocor PSB, Toronto SPV, and O'Brien-Angell valves, respectively (p
      = 0.0039). Cause of reoperation was technical in 3 (O'Brien-Angell), pannus in
      growth in 1 (O'Brien-Angell), valve tear in 1 (O'Brien-Angell), and endocarditis
      in 1 (Biocor PSB). All patients survived replacement of the xenograft with a
      stented bioprosthesis (5) or homograft root (1) and were discharged after a mean
      hospital stay of 6+/-3 days (range, 4 to 12 days). At follow-up 15+/-8 months
      after reintervention (range, 6 to 34 months), all patients are symptom-free with
      no evidence of recurrent valve obstruction, regurgitation, or infection.
      CONCLUSIONS: Reoperation for stentless xenograft failure is a rare overall event.
      Implant of the O'Brien-Angell valve may be associated with a higher prevalence of
      early reintervention because of nonstructural failure. When needed, reoperation
      on a stentless xenograft is generally a simple procedure and carries a low
      surgical risk.

PMID- 9930428
TI  - Endothelialization of biosynthetic vascular prostheses after laser perforation.
AB  - OBJECTIVE: This study was undertaken to investigate the feasibility of transmural
      capillary ingrowth into the inner surface of biosynthetic vascular prostheses
      (Omniflow, BioNova, Melbourne, Australia) through perforations created by an
      excimer laser, thus inducing an endothelial cell coverage. METHOD: Biosynthetic
      vascular prostheses (Omniflow, 10 cm length, 6 mm diameter) were perforated with
      an excimer laser (diameter of the holes 50 to 100 microm, distance 4 mm) and
      implanted into the carotid arteries of eight sheep. They were compared to
      untreated Omniflow prostheses implanted at the contralateral side. Three months
      after implantation the prostheses were explanted and evaluated by gross
      morphology, histologic examination, scanning electron microscopy, and
      immunohistochemical staining for factor VIII to identify endothelial cells.
      RESULTS: All grafts remained patent. Gross morphologic examination revealed no
      significant difference in the thrombus-free surface between perforated and
      untreated prostheses. However, scanning electron microscopy showed endothelial
      cells in the midgraft portion of all perforated prostheses, whereas collagen
      fibers, fibrin meshwork, and activated platelets formed the inner layer in six of
      eight untreated Omniflow prostheses. Transmural capillary ingrowth in the laser
      group was verified by positive factor VIII staining for endothelial cells in the
      laser channels. CONCLUSION: Spontaneous endothelialization of biosynthetic
      vascular prostheses can be achieved by transmural capillary ingrowth through
      perforations in the wall of the prostheses in an experimental sheep model.

PMID- 9930429
TI  - Evaluation of a porcine internal mammary artery (No-React II) as a small-diameter
      conduit.
AB  - BACKGROUND: The patency of biologic small-diameter vascular grafts in the
      aortocoronary position is still unsatisfactory. Most of the studies suggest that
      xenografts are to be avoided as an aortocoronary bypass. METHODS: The porcine
      internal mammary artery treated by the No-React II procedure was developed for
      use as an alternative coronary artery bypass conduit. The attempt of this study
      was to evaluate the patency and histologic changes of the porcine internal
      mammary artery in animals. Five calves underwent coronary artery bypass grafting
      with a porcine internal mammary artery graft to the right coronary artery. After
      euthanasia of the animals 103 days later, the samples of these grafts were
      studied morphologically for patency, structural changes, calcifications, and
      inflammatory and immunologic response. RESULTS: One animal died during the
      procedure as result of acute thrombosis of the porcine internal mammary artery
      graft. In the other 4 animals all grafts became occluded. In the histologic
      sections of the grafts we noted multiple calcifications and a host-graft
      immunologic reaction (severe chronic rejection). CONCLUSIONS: The present study
      demonstrates a very poor experience with the porcine internal mammary artery (No
      React II) conduit. We do not recommend this prosthesis for clinical use in
      humans.

PMID- 9930430
TI  - Medtronic intact porcine bioprosthesis: 10 years' experience.
AB  - BACKGROUND: The Medtronic Intact porcine bioprosthesis experience was evaluated
      over a period of 10 years to determine the influence of structural valve
      deterioration by valve position in various age groupings. METHODS: From 1986 to
      1996 inclusive, at three centers, 1,272 patients had the prosthesis implanted in
      1,296 procedures. The mean age of the population was 67 years (range, 9 to 91
      years). There were 836 aortic valve replacements (AVR) (64.5%), 333 mitral valve
      replacements (MVR) (25.7%), and 110 multiple valve replacements (MR) (8.5%).
      RESULTS: The early mortality was 7.3% (94 of 1,296 procedures). The early
      mortality with concomitant procedures (primarily coronary artery bypass grafting)
      was 9.8% (52 of 528) and without, 5.5% (42 of 768). The late mortality was
      4.25%/patient-year. The linearized rate of major thromboembolism was
      0.86%/patient-year. The rate of reoperation was 1.19%/patient-year and valve
      related mortality, 1.06%/patient-year. There were 36 cases of structural valve
      deterioration for aortic valve replacement (16), mitral valve replacement (15),
      tricuspid valve replacement (2), and multiple valve replacement (3). The freedom
      from structural valve deterioration for aortic valve replacement was in patients
      21 to 40 years, 62.5%+/-25.8% at 7 years; 41 to 50 years, 75.0%+/-15.3% at 7
      years; 51 to 60 years, 91.0%+/-4.5% at 8 years; 61 to 70 years, 98.7%+/-0.7% at
      10 years; and older than 70 years, 98.3%+/-1.0% at 10 years (p < 0.05). The
      freedom from structural valve deterioration for mitral valve replacement was for
      patients 41 to 50 years, 91.7%+/-8.0% at 7 years; 51 to 60 years, 85.9%+/-9.9% at
      8 years; 61 to 70 years, 86.3%+/-6.8% at 8 years; and older than 70 years,
      93.9%+/-4.8% at 8 years (not significant). CONCLUSIONS: The Medtronic Intact
      porcine bioprosthesis has acceptable freedom from structural valve deterioration
      in both the aortic and mitral positions approaching 10 years of evaluation.

PMID- 9930431
TI  - Medtronic mosaic porcine bioprosthesis satisfactory early clinical performance.
AB  - BACKGROUND: The Medtronic (Minneapolis, MN) Mosaic porcine bioprosthesis is an
      investigational prosthesis which incorporates zero-pressure fixation, aortic root
      predilation, low profile stent, and alpha oleic acid antimineralization
      treatment. METHODS: From September 1994 to August 1996, 289 patients (mean age 70
      years, range, 28 to 88 years) had 227 (78.5%) aortic valve replacements and 62
      (21.5%) mitral valve replacements. Concomitant procedures were performed in 61.2%
      (139) of aortic valve replacements and 54.8% (34) of mitral valve replacements.
      Of the aortic valve replacement group 70 (30.8%) were in the 61 to 70 age group
      and 134 (59.0%) were 71 years or older. Of the mitral valve replacements, 23
      (37.1%) were 61 to 70 years and 30 (48.4%) 71 years or older. RESULTS: The early
      mortality, overall, was 4.2% (12 of 289); for aortic valve replacement it was
      4.0% (9) and for mitral valve replacement it was 4.8% (3). The late mortality for
      aortic valve replacement was 2.6% per patient-year (3 events, 1.3% of total) and
      for mitral valve replacement it was 3.3% per patient-year (one event, 1.6% of
      total). The reoperative rate for aortic valve replacement was 3.0% per patient
      year (4), while there were no mitral valve replacement reoperations. The freedom
      from major thromboembolism was 97.3%+/-1.6% for aortic valve replacement and
      94.7%+/-3.0% for mitral valve replacement at 1 to 1.5 years. The freedom from
      reoperation was 96.7%+/-1.7% for aortic valve replacement; there was no
      reoperation for mitral valve replacement. There were no cases of structural valve
      deterioration. In the aortic position the mean systolic gradient was low,
      approximately 11 mm Hg, across all sizes (range 8 to 12 mm Hg at 3 months and 10
      to 13 mm Hg at 12 months). In the mitral position the mean diastolic gradient was
      approximately 5 mm Hg (range, 2 to 6 mm Hg) for all sizes 25 to 31 mm at the
      early and 1 year follow-up echocardiographic assessment. CONCLUSIONS: The early
      clinical performance and in vivo hemodynamics are encouraging.

PMID- 9930432
TI  - The mosaic bioprosthesis in the aortic position: hemodynamic performance after 2
      years.
AB  - BACKGROUND: The Mosaic bioprosthesis is a porcine valve combining several new
      features to improve hemodynamics and durability: a low profile stent for reduced
      flow obstruction, zero pressure fixation to maintain the natural collagen crimp,
      and the amino oleic acid antimineralization treatment to enhance durability.
      METHODS: Fifty-five Mosaic valves were implanted in the aortic position since
      February 1994. Data from these patients (group 1) were compared with data from 52
      patients who had received a Hancock Modified Orifice II aortic valve (group 2).
      The mean patient age was 72.0 (+/-5.9) years for group 1 and 76.8 (+/-4.7) years
      for group 2. Clinical examinations including transthoracic echocardiography were
      performed 6 and 24 months postoperatively. RESULTS: Mild aortic insufficiencies
      were found in 2 patients in group 1 and in 3 patients in group 2. There were no
      embolic or bleeding complications. One Mosaic patient required reoperation due to
      mitral insufficiency. During the reoperation, a small (approximately 3 mm)
      thrombus was noted on the outflow side of a Mosaic cusp. The valve was removed
      and replaced prophylactically. In the 2-year follow-up, hemodynamic measurements
      showed mean pressure gradients of 12.4 mm Hg for the 21 mm, 11.3 mm Hg for the 23
      mm, and 15.4 mm Hg for the 25 mm prostheses in the Hancock group. In the Mosaic
      group, mean pressure gradients were 14.8 mm Hg for the 21 mm, 10.9 mm Hg for the
      23 mm, and 11.5 mm Hg for the 25 mm valves. Differences between pressure
      gradients and effective orifice areas of the Hancock and the Mosaic valves were
      not statistically significant. Early mortality in group 1 was 3.6% and in group 2
      3.8%. Overall mortality was 12.7% and 13.5%, respectively. CONCLUSIONS: The
      Mosaic valve has low pressure gradients for all sewing ring diameters. Compared
      with the Hancock Modified Orifice valve, there was no statistically significant
      gradient difference but a tendency toward better hemodynamics was noted in the
      Mosaic group after 2 years.

PMID- 9930433
TI  - Hemodynamic features of the freestyle aortic bioprosthesis compared with stented
      bioprosthesis.
AB  - BACKGROUND: The Freestyle prosthesis is a new stentless aortic bioprosthesis.
      Anticipated benefits are improved hemodynamics and increased longevity. METHODS:
      Doppler echocardiograms were performed early and at 3 to 6 months, 1 year, and 2
      years after operation in 157 patients (69 men, 88 women, aged 48 to 85 years)
      with this prosthesis, and results were compared with hemodynamic data in patients
      with Intact and Mosaic stented bioprostheses. RESULTS: Distinctive features of
      the prosthesis compared with stented prostheses are (1) an increase in effective
      orifice area (+0.15+/-0.26 cm2; p < 0.05) and a decrease in mean gradient (-3.5+/
      4.0 mm Hg; p < 0.001) during the first 3 to 6 months postoperatively and
      stabilization thereafter; (2) a markedly lower mean gradient at 1 year after
      operation (average, 6+/-4 mm Hg) than in stented prostheses (Intact, 22+/-8 mm
      Hg; Mosaic, 12+/-6 mm Hg); (3) in contrast to stented prostheses, in vivo
      effective orifice areas much lower (-0.91+/-0.35 cm2) than those calculated in
      vitro; (4) as in stented prostheses, the indexed effective orifice area (cm2/m2)
      is the best predictor (r = 0.77 at 1 year) of the mean gradient after operation;
      and (5) similar incidence of aortic regurgitation (trivial or mild, 34% versus
      29% in Intact). CONCLUSIONS: The hemodynamics of the Freestyle are very
      satisfactory and represent a marked improvement in comparison to stented
      prosthesis.

PMID- 9930434
TI  - The stentless Cryolife-O'Brien aortic porcine xenograft: a five-year follow-up.
AB  - BACKGROUND: The 5-year follow-up of CryoLife-O'Brien stentless porcine aortic
      valve xenografts is presented. METHODS: From August 1991 to August 1996, the
      valve was used in 366 patients. Patients' ages ranged from 18 to 90 years (mean,
      73+/-6 years). Survivors were monitored with Doppler echocardiography before
      discharge, at 6 months, and then annually by the referring cardiologist.
      Operative and long-term mortality and morbidity were collected using the Edmunds
      guidelines for reporting morbidity and mortality after cardiac valvular
      operations. RESULTS: The study was completed during a 6-month period with a 96.5%
      follow-up, comprising 999 patient-years for a mean follow-up period of 27 months
      (range, 3 to 64 months). Operative mortality was 6.5%. Linearized rates per
      patient-year for complications were as follows: structural valve deterioration
      (0%); thromboembolism (0.5%); prosthetic valve endocarditis (0.2%); valve
      reoperation (0.8%); and valve-related mortality (0.2%). Sixteen late deaths have
      occurred. The actuarial survival rate at 5 years was 83%+/-3.5%. CONCLUSIONS: The
      Cryolife-O'Brien stentless valve has given excellent early hemodynamic and 5-year
      results.

PMID- 9930435
TI  - Early calcific stenosis of the aortic sorin pericarbon valve implanted in the
      elderly.
AB  - BACKGROUND: We reviewed our experience with the Sorin Pericarbon (Sorin,
      Saluggia, Italy) valve implanted in the aortic position. METHODS: From January
      1990 to January 1996, 143 consecutive patients had a Pericarbon valve implanted
      in the aortic position. The mean age was 75+/-5 years. Seventy-eight patients
      (55%) were in New York Heart Association (NYHA) class III or IV. Sixty patients
      (42%) had one or more concomitant procedures (51 coronary artery bypass grafting
      [CABG], 7 carotid endarterectomies, 9 others). RESULTS: The hospital mortality
      rate was 12% (17 of 143 patients). The follow-up was 100% complete and the median
      time was 42 months (range, 2 to 79 months). There were 36 late deaths, 20 being
      cardiac-related: 5 non-valve-related, 11 valve-related, and 4 sudden unexpected
      deaths. The 5-year actuarial survival was 57%+/-5%. There were 6 early valve
      failures related to a calcific stenosis at a median time of 36 months (range, 5
      to 66 months). Three patients had to undergo another operation and one of these
      patients died. One patient died the day before the planned reoperation and 2
      patients are followed with a symptomatic aortic stenosis but refuse reoperation.
      Freedom from structural deterioration was 93%+/-3% at 4 years. Echocardiographic
      examination was obtained in 73 patients at a median time of 42 months (range, 4
      to 79 months). Four additional asymptomatic patients were found to have
      calcifications of their prosthesis. The 5-year freedom from thromboembolic events
      and from endocarditis were, respectively, 87%+/-5% and 92%+/-3%. CONCLUSION: The
      surprisingly high rate of early failure due to calcific stenosis and of
      thromboembolic events of the Pericarbon valve implanted in the aortic position in
      the elderly made us discontinue its use in our institution.

PMID- 9930436
TI  - Carpentier-Edwards pericardial bioprosthesis in aortic or mitral position: a 12
      year experience.
AB  - BACKGROUND: The first generation of pericardial valves was withdrawn from the
      market for a high rate of premature failure. With an original design, Carpentier
      Edwards pericardial valves promised improved results. METHODS: Seven hundred
      eighty-seven patients who underwent isolated aortic valve replacement and 182
      patients who underwent isolated mitral valve replacement between July 1984 and
      December 1995 with Carpentier-Edwards pericardial bioprostheses in our
      institution were followed up. The patients' mean age was 68.3 (aortic valve
      replacement, AVR) and 63.9 (mitral valve replacement, MVR) years. All but five
      AVR patients were followed up for an average of 4.7 years after operation, with a
      total follow-up of 3,624 patient-years. All patients with MVR were followed up
      for an average of 5.3 years after operation, with a total follow-up of 969
      patient-years. RESULTS: After 12 years, actuarial survival rate is 53% for AVR
      and 54% for MVR. Freedom from valve-related complications for aortic versus
      mitral valve replacement is, respectively, 68% and 55%, freedom from valve
      related death is 84% and 85%, freedom from thromboembolism 87% and 94%, and
      freedom from endocarditis 97% and 94%. The behavior of the aortic valve is better
      than that of the mitral valve: freedom from reoperation is 92% and 76%,
      respectively; freedom from valve failure is 94% and 78%. Age is an important
      factor, especially in the mitral position: freedom from valve failure is 52% in
      patients younger than 60 years and 100% in patients older than 60 years.
      CONCLUSIONS: With a low rate of valve-related events at 12 years and a low rate
      of structural deterioration, this prosthesis is a reliable choice for AVR and in
      patients over 60 years for MVR. A more durable mitral bioprosthesis is needed for
      patients younger than 60 years.

PMID- 9930437
TI  - Aortic root replacement with a pulmonary autograft in young adults: medium-term
      results in 70 patients.
AB  - BACKGROUND: Pulmonary autograft aortic valve replacement has been introduced in
      our institution in selected adult patients in light of the known disadvantages
      and limitations of conventional prosthetic valves. METHODS: We prospectively
      evaluated the use of the pulmonary autograft in a series of 70 young adults
      (31.2+/-8.7 years, range 16 to 49 years) operated on from March 1992 to April
      1997 with aortic root replacement only. RESULTS: There were no in-hospital deaths
      and two noncardiac-related late deaths during follow-up of up to 62 months (mean
      33 months). Thromboembolic complications were not observed. One patient required
      reoperation for infective endocarditis 4.3 years after surgery. Discharge echo
      Doppler studies showed normal autograft and allograft valve function. Serial echo
      Doppler studies showed no significant progression of aortic insufficiency and no
      dilatation of the autograft. A severe stenosis of the pulmonary allograft
      developed in 1 patient. CONCLUSION: Aortic root replacement with a pulmonary
      autograft, although more complex than conventional prosthetic valve replacement,
      is a safe, effective, and reproducible procedure in properly selected adult
      patients. Long-term results remain to be evaluated.

PMID- 9930438
TI  - Cardiopulmonary response to maximal exercise in young athletes following the Ross
      procedure.
AB  - BACKGROUND: Aortic prosthetic devices offer limitations that make them less than
      optimal valve substitutes because the vast majority are innately obstructive,
      especially at increased levels of hemodynamic function. The present study is
      designed to demonstrate the hemodynamics of the pulmonary autograft in 11
      conditioned athletes who have undergone the Ross (pulmonary autograft) procedure.
      Data was compared to a group of 13 age-matched "normal athletes." METHODS: All
      the Ross athletes had undergone the autograft procedure using the root
      replacement technique and were at least 3 months into their postrecovery phase.
      All athletes (both normal and Ross) underwent resting transthoracic echo followed
      by maximal exercise stress test (modified Bruce protocol) to exhaustion. Post
      operative transesphogeal echocardiogram obtained within 90 seconds documented
      aortic valve gradient and velocity across the aortic valve. RESULTS: In the Ross
      athlete group, maximum heart rate was 188 beats per minute, peak aortic valve
      gradient at rest (mm Hg) 7.69 (mean), velocity across the aortic valve at rest
      (cm per second) 129.40 (mean), peak aortic valve gradient at maximal exercise (mm
      Hg) 16.30 (mean), velocity across the aortic valve at maximal exercise (cm per
      second) 190.00 (mean). In the normal athlete group, maximum heart rate was 176
      beats/minute, peak aortic valve gradient at rest (mm Hg) 5.97 (mean), velocity
      across the aortic valve at rest (cm per second) 120.54 (mean), peak aortic valve
      gradient at maximal exercise (mm Hg) 14.61 (mean), velocity across the aortic
      valve at maximal exercise (cm per second) 190.23 (mean). CONCLUSION: The
      pulmonary autograft exhibits hemodynamic characteristics similar to the normal
      human aortic valve under conditions of enhanced cardiac output.

PMID- 9930439
TI  - Effect of papillary muscle position on mitral valve function: relationship to
      homografts.
AB  - BACKGROUND: We used a finite element model to determine the effect of papillary
      muscle position on the stress distribution in the mitral valve. METHODS: A normal
      model was modified to move the posteromedial papillary muscle outward by either
      2.5 mm or 5.0 mm. Next, the thickness was increased by 20%, simulating diseased
      tissue. Physiologic loading pressures were applied, and leaflet stress, chordal
      stress, and coaptation results were analyzed. RESULTS: Displacement of the
      posteromedial papillary muscle increased the leaflet stresses and altered the
      normal stress patterns. The displacement also restricted the leaflets from
      closing completely, allowing regurgitation. Combining increased thickness with
      papillary displacement decreased the stresses slightly. However, the amount of
      leaflet coaptation was further decreased, creating larger gaps for regurgitation.
      In all models, the stresses in the chordae were increased in the marginal chordae
      and decreased in the basal chordae, demonstrating a transfer of stress.
      CONCLUSIONS: Papillary muscle displacement creates abnormal valve stresses, and
      the potential for significant regurgitation. Papillary-chordal-leaflet geometry
      must be maintained in partial or complete mitral homograft replacement.

PMID- 9930440
TI  - The Ross Procedure: current registry results.
AB  - BACKGROUND: The pulmonary autograft procedure for the treatment of aortic valve
      disease was developed and performed by Ross in 1967. The results he published in
      1987 prompted increasing interest in the procedure. The International Registry of
      the Ross Procedure was established in 1993 to further examine longitudinal
      clinical outcomes. METHODS: The results from the Ross registry document the
      continued and growing interest in the procedure with 2,523 patients currently
      enrolled, representing 122 centers and 166 surgeons worldwide. RESULTS: Mortality
      (1987 to present) reported in the registry is 2.5%. It should be noted that
      follow-up stands at 70%. The most important issues for the registry to track are
      the incidence of reoperation for autograft failure and the fate of the pulmonary
      homograft. Reoperation for all valve-related problems is low (5.4%), with an
      autograft explant rate of 1.9%. Overall registry data indicate that the right
      ventricular outflow tract revision rate is 2.8%, with this decreasing by half to
      1.3% in the 1987 to present subgroup. CONCLUSIONS: Rigorous analysis of outcomes
      is difficult with registry follow-up currently at 70%; however, the general
      conclusions derived from the registry are supported by other individual series
      with excellent follow-up. Success of the registry depends on judicious efforts by
      all participating surgeons and coordinators in documenting long-term patient
      results and reporting them to the registry.

PMID- 9930442
TI  - Comparison of Ross procedures and aortic valve allografts in children.
AB  - BACKGROUND: The Ross procedure is useful, but at times an allograft valve is the
      only alternative to a mechanical aortic prosthesis. Since 1994 the Ross procedure
      or aortic allograft replacement has been used exclusively for aortic valve
      replacement at our institution. METHODS: Demographic, clinical, and
      echocardiographic data of 23 consecutive Ross and 8 allograft patients were
      compared. RESULTS: Groups were similar in age and weight. The Ross group had
      fewer prior operations. There were no deaths or major complications in either
      group. The Ross group had no late complications of the autograft but 1
      reoperation for pulmonary allograft stenosis. In the allograft group there was
      one reoperation for allograft insufficiency. Echocardiography was performed 2 to
      11 days (mean, 4.3 days) after operation and 1 to 28 months (mean, 10.2 months)
      later. In the Ross group left ventricular wall thickness (mm) decreased from 11.0
      +/- 2.3 to 7.8+/-1.7 (p < 0.0001), and left ventricular outflow tract maximal
      systolic velocity (m/sec) decreased from 1.9 +/-0.6 to 1.4+/-0.4 (p = 0.0001). In
      the allograft group left ventricular wall thickness (mm) decreased from 10.5 +/
      2.6 to 9.0+/-2.6 (not significant), and left ventricular outflow tract maximal
      systolic velocity (m/sec) increased from 1.5+/-0.9 to 1.9+/-0.7 (not
      significant). CONCLUSIONS: The Ross procedure results in significant improvement
      in left ventricular wall thickness and outflow tract velocity not seen in
      allograft aortic valve replacements. The Ross procedure remains the preferred
      operation for children requiring aortic valve replacement.

PMID- 9930441
TI  - Treated bovine and autologous pericardium for aortic valve reconstruction.
AB  - BACKGROUND: To determine the differences in clinical behavior of bovine versus
      autologous pericardium, all consecutive patients undergoing aortic valve
      reconstruction were reviewed. METHODS: Between October 1988 and December 1995, 91
      patients (mean age 30 years) underwent reconstruction with bovine (n = 27) or
      autologous (n = 64) pericardium. RESULTS: There were 2 hospital deaths, 5 late
      deaths, and no embolic events. Dysfunction of the aortic reconstruction required
      reoperation in 6 bovine (infection 1, fibrocalcific 5) and in 5 autologous
      (infection 3, annulus dilatation 1, commissural tear 1). Actuarial survival and
      freedom from structural deterioration at 8 years were 82.2%+/-9.6% and 76.2%+/
      10.7% for bovine and 91.05%+/-3.96% and 96.8%+/-2.25% for autologous pericardium,
      respectively. The last Doppler echocardiographic study showed a mean
      regurgitation (1 to 4+) and gradient in the bovine pericardium of 1.25+/-and 20.7
      mm Hg and in the autologous pericardium of 1+ and 7.7 mm Hg. CONCLUSIONS: Aortic
      valve reconstruction with pericardium can be safely performed with low
      thromboembolic rate. At 8 years follow up, there is a difference in favor of the
      autologous pericardium.

PMID- 9930443
TI  - Intermediate follow-up of right ventricular outflow tract reconstruction with
      allograft conduits.
AB  - BACKGROUND: Allograft conduits are among many varieties of material used for
      right ventricular outflow tract reconstruction. They invariably need to be
      replaced due to growth of the patient or conduit failure. METHODS: From June 1984
      to June 1996, a total of 76 patients underwent reconstruction of the right
      ventricular outflow tract with an allograft conduit: 51 aortic and 25 pulmonary.
      The median age, weight and conduit size at surgery were 37 months (range, 0.2 to
      228 months), 12.4 kg (range, 2.9 to 61.4 kg), and 17 mm (range, 8 to 26 mm),
      respectively. RESULTS: The hospital mortality was 5.3% (4 of 76 patients) and 2
      patients died at 9 and 78 months follow-up. The median follow-up was 61 months
      (range, 2 to 132 months). Reoperation was necessary in 22 patients (28.9%) at a
      median interval of 50.5 months (range, 3 to 109 months) and the median conduit
      size was 21 mm (range, 12 to 23 months). There was no mortality. Freedom from
      reoperation at 64 months was 49.5% for conduits 15 mm and smaller, and 73.3% for
      conduits 16 mm and larger. Analysis by age shows freedom from reoperation at 64
      months of 49.4% and 74.5% for patients younger than and older than 2 years,
      respectively. At 54 months there was no statistical difference in freedom from
      reoperation between pulmonary and aortic allografts. CONCLUSION: Right
      ventricular outflow tract reconstruction with allograft conduits results in a
      high reoperation rate at 4 years but provides significantly longer freedom from
      reoperation with conduits larger than 15 mm or in patients over 24 months of age.

PMID- 9930444
TI  - Porcine stentless valve/bovine pericardial conduit for right ventricle to
      pulmonary artery.
AB  - BACKGROUND AND OBJECTIVES: We assessed the long-term outcome of a glutaraldehyde
      preserved bovine pericardial conduit containing a stentless composite porcine
      aortic valve. METHODS: Between November 1985 and May 1995, 33 stentless porcine
      valves attached to bovine pericardial conduits were used in 33 patients with
      complex congenital cardiac malformations. These patients required a conduit
      between the right ventricle and the pulmonary artery because of an absent or
      inadequate pulmonic artery. All patients were approached by midsternotomy. One
      patient with pulmonic atresia and an interventricular septal defect required left
      thoracotomy for ligation of collaterals. RESULTS: Of the initial 33 patients,
      clinical follow-up was performed in 23 discharged patients (70%) for 1.7 to 10.5
      years. The echo-Doppler analysis performed in each of the 23 followed patients
      showed excellent conduit and valve function in all but 4 patients, in whom a
      valve gradient of 60 mm Hg was noted. There was no tissue structural failure
      noticed in this study. CONCLUSIONS: The SJM Biocor (Belo Horizonte, Brazil)
      bovine pericardial stentless valved conduit performed well as a substitute for
      the right ventricle to pulmonary artery connection.

PMID- 9930445
TI  - Truncus arteriosus: ten-year experience with homograft repair in neonates and
      infants.
AB  - BACKGROUND: Early complete repair of truncus arteriosus with homograft
      reconstruction of the right ventricular outflow tract was performed and long-term
      results were evaluated. METHODS: Review of 46 consecutive patients with truncus
      arteriosus who underwent primary correction between June 1987 and May 1997 was
      performed. Ages ranged from 21 days to 7.2 years (median, 62 days) and weights
      from 1.8 to 21.5 kg (median, 3.4 kg). Ten patients were operated on before 1
      month of age, 20 between 1 and 3 months, 13 between 3 months and 1 year, and 3 at
      an older age. Associated cardiac conditions were encountered frequently, the most
      common being coronary artery anomalies (n = 16), truncal valve incompetence (n =
      12), and interrupted aortic arch (n = 5). The right ventricular outflow tract was
      reconstructed with an aortic (n = 28) or a pulmonary homograft (n = 18). RESULTS:
      There were two hospital deaths (4.3%). Both patients had severe truncal valve
      regurgitation and interrupted aortic arch together with other unfavorable
      conditions. Survival in uncomplicated truncus arteriosus was 100%. Follow-up was
      from 3 months to 10 years (mean, 36 months). There was one late death 4 months
      after the initial repair, presumably because of cardiac reason. Actuarial
      survival was 93% at 4 months and beyond. Actuarial freedom of reoperation in the
      27 hospital survivors with aortic homografts was 43% at 75 months; it was 73% at
      62 months in the 17 patients surviving with pulmonary homografts. CONCLUSIONS:
      Neonatal or early infancy complete repair is the treatment with the best
      potential for survival. The homograft remains our conduit of choice to establish
      continuity between the right ventricle and the pulmonary artery. Management of
      severe truncal valve incompetence remains a surgical challenge.

PMID- 9930446
TI  - Aortic root replacement in adolescents and young adults: composite graft versus
      homograft or autograft.
AB  - BACKGROUND: Aortic root replacement (ARR) is a technically demanding procedure
      that can be performed using a variety of prosthetic devices. Root replacement in
      the young, but grown-up, patient poses unique problems in terms of the long-term
      outcome and active lifestyle that must be guaranteed by this operation. To
      identify the "ideal" substitute for ARR in the young, clinical results in
      teenagers and young adults (<35 years) operated on in the past two decades were
      reviewed. METHODS: Thirty-eight patients younger than 35 years underwent ARR
      between January 1980 and December 1996. Eighteen patients, aged 30+/-5 years, had
      ARR with composite graft (group 1), whereas 20 patients, aged 28+/-6 years, had
      ARR with aortic homografts or pulmonary autografts (group 2). Primary indication
      for the operation was aortic insufficiency with anuloaortic ectasia (12 of 18) in
      group 1 and aortic insufficiency with or without anuloaortic ectasia (16 of 20)
      in group 2. Urgent ARR was required in 3 (17%) group 1 patients and 1 (5%) group
      2 patient (p = 0.01). RESULTS: Operative deaths were 2 (11%) in group 1, caused
      by hemorrhage and low output, and none in group 2. There were 4 (25%) late deaths
      in group 1, caused by embolism (2), hemorrhage, and myocardial infarction, and 1
      (5%) in group 2, caused by arrhythmia. Survival was 81% +/- 9%, and 55%+/-18% at
      2 and 10 years in group 1 versus 94%+/-5% at 2 years in group 2 (p = 0.04).
      Freedom from valve-related events was 93%+/-6% and 62%+/-18% at 2 and 10 years in
      group 1 versus 100% at 2 years in group 2 (p = 0.02). Freedom from reoperation in
      group 1 was 75% +/- 22% at 10 years, whereas no reoperations were done in group
      2. Seven (58%) group 1 patients versus 1 (5%) group 2 patient were on cardiac
      medications (p = 0.001), and 11 (92%) group 1 patients versus no group 2 patients
      were on warfarin therapy at follow-up. All survivors were back to school or prior
      employment. CONCLUSIONS: Survival early after ARR does not differ depending on
      the type of prosthesis. Valve-related events are common, and reoperation may be
      needed late after ARR with composite grafts. Despite limited follow-up with
      biologic devices, the prevalence of complications with composite grafts makes
      homograft or autograft ARR preferable in adolescents and young adults.

PMID- 9930447
TI  - Aortic homografts versus mechanical valves in aortic valve replacement in young
      patients: a retrospective study.
AB  - BACKGROUND: Whether aortic homografts (AH) or mechanical devices (MD) are the
      valves of choice for aortic valve replacement in young patients (age 20 to 50
      years) is unclear. Hence, we examined all aortic valve replacements performed
      with AH and MD in a retrospective study. METHODS: Between 1988 and 1995, 45
      patients (mean age, 38.6+/-8.5 years) underwent aortic valve replacement with an
      AH and 40 patients (mean age, 42.0+/-7.2 years) with an MD. Patients' demographic
      data were comparable in all respects, except acute endocarditis, which was an
      absolute indication for the use of an AH. RESULTS: The mean follow-up time was
      51.7+/-22.6 months for AH versus 44.6+/-26.9 months for MD (not significant).
      There were significant differences in postoperative outcome among the two groups
      (p < or = 0.05): perioperative death (4 versus 0 for AH and MD, respectively);
      reoperation (8 for AH versus 0 for MD); and endocarditis (5 versus 0 for AH and
      MD). There were higher incidences of embolism (2 versus 0) and hemorrhage (2
      versus 0) in MD compared with AH. Only late death was comparable among the two
      groups with 5 patients in each group. CONCLUSIONS: The mechanical valves in our
      midterm follow-up are superior to homografts. However, embolic and hemorrhagic
      complications in MD are continuously impending and cumulative during a long-term
      follow-up. The surprisingly high rate of endocarditis in the AH group is only
      partly caused by the indication: 2 cases were recurrent, but there were also 2
      new onsets of endocarditis. In 4 cases structural deterioration was responsible
      for reoperation. Aortic valve replacement with aortic homografts showed a rather
      unfavorable midterm outcome in this selected group of young patients. A
      surprisingly high rate of graft endocarditis and structural deterioration led to
      subsequent reoperations. Although our results with mechanical valves are
      satisfying, embolism and hemorrhage are impending risk factors for many years to
      come in these young patients.

PMID- 9930448
TI  - Altered collagen concentration in mitral valve leaflets: biochemical and finite
      element analysis.
AB  - BACKGROUND: Ischemic mitral regurgitation or ventricular wall motion
      abnormalities will alter the stress distribution in the mitral valve. We
      hypothesize that in response, the regional collagen concentration will be altered
      and will significantly impact the stress distribution in the mitral valve.
      METHODS: Two sheep served as normal (sham) controls. Two other sheep had coronary
      ligation resulting in abnormal ventricular wall motion. Four sheep underwent
      ligation to infarct the posteromedial papillary muscle, resulting in ischemic
      regurgitation. After 4 or 8 weeks, the mitral valves were excised, and the
      anterior leaflet sections were subjected to an assay for collagen concentration.
      Next, in a finite element model, to simulate changes in collagen concentration,
      the tissue stiffness was increased by 20%, and then decreased by 20%. In another
      model, the thickness of the tissue was increased by 20%, and then combined with
      decreased tissue stiffness. Physiologic loading pressures were applied, and
      leaflet stress, chordal stress, and coaptation results were analyzed. RESULTS:
      The average collagen concentration in the normal sheep leaflets was 59.2% (dry
      weight), 50.6% in the ischemic controls, and 45.8% in the papillary muscle
      infarct group. Collagen concentration was greatest at the midline and decreased
      toward the commissures. Increased tissue stiffness resulted in increased leaflet
      and chordal stresses, as well as reduced coaptation. Decreased stiffness resulted
      in the opposite. Increased tissue thickness reduced leaflet and chordal stresses,
      but also reduced coaptation. The combination of increased tissue thickness and
      decreased stiffness demonstrated the greatest reduction in leaflet and chordal
      stress, while maintaining normal leaflet coaptation. CONCLUSIONS: The observed
      changes may demonstrate an early effort to compensate for increased leaflet
      stress. Microstructural alterations may demonstrate an early effort to compensate
      for altered physiologic loading to reduce stress and maintain coaptation. It is
      crucial in repairing or partially replacing thickened tissue that normal geometry
      and physiology be restored.

PMID- 9930450
TI  - Effect of HLA mismatching and antibody status on "homovital" aortic valve
      homograft performance.
AB  - BACKGROUND: Recipients of "homovital" aortic valve homografts are known to
      produce specific antibodies to human leukocyte antigen (HLA) determinants present
      on the cellular compartment of the valve tissue; however, the clinical
      significance of these antibodies is unknown. Data from 182 patients receiving
      homovital aortic valve homografts has been analyzed to determine the impact of
      HLA disparity and HLA antibody production on survival and function of the
      homograft. METHODS: Human leukocyte antigen mismatch data were available for 127
      patients (mean follow-up, 6.02+/-0.26 years). Two patients were considered well
      matched for HLA A+B antigens (zero or one mismatch) compared with 125 poorly
      matched (two to four mismatches). Nine patients had a zero HLA-DR mismatch
      compared with 52 with one mismatch and 59 patients completely mismatched for DR
      antigens. RESULTS: There was no significant association between the degree of HLA
      mismatch for either class I or class II antigens whether the loci were considered
      alone or in combination (ie, A, B, DR, AB, or ABDR mismatching) with markers of
      long-term valve function including patient mortality, reoperation, valve
      degeneration, valve stenosis, presence of regurgitation, and postoperative New
      York Heart Association class. One hundred thirty-six of 167 (82%) were found to
      have produced antibodies after operation (mean time after operation, 6.42+/-0.58
      years). In 61 cases both antibody specificity and donor HLA typing was available.
      In 92% of these, the antibodies were of the IgG subclass and were specific for
      the HLA class I molecules of the donor. The presence of HLA antibodies was
      associated with an increase in the frequency of mild valve stenosis (not
      significant) compared with those patients who did not develop HLA antibodies
      (antibody negative = 9.7%; panel reactive antibodies <50% = 29.1%; and panel
      reactive antibodies >50% = 22.2%; not significant). There was also an increased
      prevalence of valve degeneration associated with HLA antibodies. The actuarial
      freedom from valve degeneration for the 35 HLA antibody-negative patients was
      100% at 1, 5, and 10 years compared with 100% at 1 year, 97% at 5 years, and 92%
      at 10 years for 55 patients with panel reactivity less than 50%, and 98% at 1
      year, 94% at 5 years, and 88% at 10 years for the 77 patients who were highly
      sensitized (not significant). There was no correlation with other markers of long
      term valve function. CONCLUSIONS: The influence of the immune response on valve
      function requires further studies involving large numbers of patients followed
      for a longer period of time. We believe prospective matching for HLA antigens is
      warranted to produce a well-matched cohort of patients for analysis and to reduce
      antibody sensitization, which would help to clarify this issue.

PMID- 9930449
TI  - In vitro testing of bioprostheses: influence of mechanical stresses and lipids on
      calcification.
AB  - BACKGROUND: Structural valve deterioration of bioprostheses is mainly caused by
      the progressive development of calcification. Mechanical stresses or lipid
      deposits in porcine aortic leaflets have been proposed as major factors
      contributing to the calcification process. METHODS: A new test protocol
      consisting of nondestructive holographic interferometry, which allows a
      quantitative deformation analysis of heart valves, and accelerated dynamic in
      vitro calcification was used. The rapid calcification fluid contained a final
      combined calcium and phosphorus concentration of 130 (mg/dL)2 in barbital buffer
      solution. The calcification of 32 bioprostheses donated by different
      manufacturers (SJM Bioimplant, Biocor standard, Biocor No-React, Carpentier
      Edwards SAV, Bravo, pericardial prototype) was assessed after up to 25 x 10(6)
      cycles by microradiography and the areas of calcification were compared with the
      holographic interferograms. The distribution of lipid droplets of four porcine
      prostheses were visualized by Sudan III stain before the calcification process.
      RESULTS: Most of the tested bioprostheses had areas presenting with stress
      concentrations, and the dynamic in vitro testing resulted in leaflet
      calcification corresponding to the holographic irregularities. A strong
      correlation between calcification and stress distribution or lipid accumulation
      was found (r = 0.72; r = 0.81, respectively). After 19 x 10(6) cycles, the
      Carpentier-Edwards SAV and the pericardial valves had significantly less
      calcification than other prostheses tested (p = 0.003), but the variation among
      individual prostheses from the same manufacturer was even more pronounced.
      CONCLUSIONS: Mechanical stresses or lipid accumulation seems to play an important
      role in the calcification process of bioprostheses. Quality control of
      bioprosthetic valves using holographic interferometry has the potential to
      predict calcification before implantation.

PMID- 9930451
TI  - Histologic and immunohistochemical responses after aortic valve allografts in the
      rat.
AB  - BACKGROUND: Human aortic valve allografts elicit a cellular and humoral immune
      response. It is not clear whether this is important in promoting valve damage. We
      investigated the changes in morphology, cell populations, and major
      histocompatibility complex antigen distribution in the rat aortic valve
      allograft. METHODS: Fresh heart valves from Lewis rats were transplanted into the
      abdominal aorta of DA rats. Valves from allografted, isografted, and
      presensitized recipient rats were examined serially with standard morphologic and
      immunohistochemical techniques. RESULTS: In comparison with isografts, the
      allografts were infiltrated and thickened by increased numbers of CD4+ and CD8+
      lymphocytes, macrophages, and fibroblasts. Thickening of the valve wall and
      leaflet and the density of the cellular infiltrate was particularly evident after
      presensitization. Endothelial cells were frequently absent in presensitized
      allografts whereas isografts had intact endothelium. Cellular major
      histocompatibility complex class I and II antigens in the allograft were
      substantially increased. A long-term allograft showed dense fibrosis and
      disruption of the media with scattered persisting donor cells. CONCLUSIONS: The
      changes in these aortic valve allograft experiments are consistent with an
      allograft immune response and confirm that the response can damage aortic valve
      allograft tissue.

PMID- 9930452
TI  - Effect of antibiotic pretreatment on immunogenicity of human heart valves and
      component cells.
AB  - BACKGROUND: For many years valves have been sterilized with high-dose antibiotics
      before implantation, but now there is an increasing trend to using "homovital"
      valves, which have been exposed to very low dose antibiotics. METHODS: To
      investigate the immunogenicity of valve tissue, before and after exposure to high
      and low-dose antibiotics, peripheral blood mononuclear cells and human allogenic
      T cells were cocultured with antibiotic-treated valve discs, cultured valve
      endothelial cells, and fibroblasts. Proliferation was measured by uptake of
      thymidine labeled with hydrogen 3. RESULTS: Untreated tissue pieces stimulate
      peripheral blood mononuclear cells (4,080+/-980 cpm) at day 0 with similar
      results after 1 day in Hank's balanced salt solution (4,272.4+/-1,307 cpm)
      reducing to 2,442+/-926 cpm after 3 days and 1,111+/-255 cpm after 5 days;
      antibiotic-treated pieces are less immunogenic after 1 (2,560+/-403 cpm), 3
      (1,550+/-60 cpm), 5 (717+/-295 cpm), and 7 days (633+/-174 cpm) in homovital
      solution, whereas sterilized pieces are not immunogenic (184+/-96 cpm) after only
      1 day in strong antibiotics. Histologic analysis showed that this corresponds to
      a reduction of class I and class II expression by human valve endothelial cells.
      Human valve endothelial cells but not fibroblasts are capable of causing direct
      stimulation of CD4+ T cells. However, human valve endothelial cells poorly
      stimulate CD4+ T cells after incubation in homovital solution for 24 hours.
      CONCLUSIONS: This study shows that valve tissue is immunogenic and this
      immunogenicity is mediated mainly by endothelial cells. However, the
      immunostimulatory potential of the valve can be reduced by incubating the
      solution in an antibiotic cocktail.

PMID- 9930453
TI  - Tissue chimerism in human cryopreserved homograft valve explants demonstrated by
      in situ hybridization.
AB  - BACKGROUND: The presence of viable cells may contribute to increased homograft
      valve durability. These cells may be of infiltrating recipient or persisting
      donor origin. In this study, in situ hybridization was used to assess the origin
      of cells in cryopreserved homograft valve explants. METHODS: A total of 10
      homografts with a donor-recipient gender mismatch were acquired from patients
      whose graft had been explanted at reoperation or at autopsy. The period of
      implantation varied from 14 days to 70 months. Frozen sections were made and
      alternately examined with hematoxylin and eosin staining and in situ
      hybridization. Male cells were distinguished from female using a biotinylated Y
      chromosome-specific deoxyribonucleic acid probe. RESULTS: No endothelial cells
      were found. Thirty percent of the leaflets showed large acellular zones and 30%
      were completely acellular. The homograft arterial wall was occupied by a vast
      majority of penetrating host fibroblasts in 80% of the studied specimens. Donor
      and recipient cells were coexistent in the wall in 60% of the studied specimens
      and in 50% of the leaflets. In 30% only host cells could be identified.
      CONCLUSIONS: This finding of tissue chimerism may lead to new insights in
      homograft pathology. The technique of in situ hybridization may provide an
      indispensable contribution in further homograft research.

PMID- 9930455
TI  - Infrared spectroscopy in the evaluation of the process of calcification of
      valvular bioprostheses.
AB  - BACKGROUND: The methods currently used to analyze the process of calcification of
      bioprostheses give only global information on calcium deposition. We investigated
      the potential advantage of infrared spectroscopy, which makes it possible to
      analyze the various components of the calcification process, ie, lipids,
      proteins, and calcium deposits. METHODS: Sixty porcine aortic leaflets were fixed
      in 0.6% glutaraldehyde and then subsequently implanted in 10-day-old Wistar rats.
      The valve leaflets were removed 2, 7, 14, 21, 35, and 56 days after implantation.
      RESULTS: Before implantation infrared spectroscopic analysis revealed the
      presence of proteins only. On day 2 after implantation, all valves showed minor
      lipid deposits. On day 7, amorphous calcium phosphate was detected. Between days
      7 and 14, crystalline forms of calcium phosphate appeared and amorphous calcium
      phosphate progressively changed into carbapatite over the 56-day period.
      CONCLUSIONS: Infrared spectroscopy yields valuable additional information on the
      nature and kinetics of the various components of glutaraldehyde-treated tissues
      after implantation. It may prove to be important in the evaluation of new
      techniques of calcium mitigation.

PMID- 9930454
TI  - Postimplantation leaflet cellularity of valve allografts: are donor cells
      beneficial or detrimental?
AB  - BACKGROUND: The theory that "viable" valve grafts have superior durability
      because the donor cell population of the leaflets survives implantation and
      functions normally, thus maintaining leaflet integrity, is still not definitively
      proven. The postulate has been investigated for grafts produced and used at Green
      Lane Hospital by examining a series of 155 removed at reoperation following up to
      21.3 years of implantation. METHODS: Leaflet cellularity at explantation was
      assessed histologically. An additional 55 cases were also assessed by tissue
      culture. Cell origin for six positive cultures was determined by comparison of
      DNA of the culture with that of the recipient's blood cells. RESULTS: Grafts
      known to be nonviable at implantation lacked leaflet fibroblasts but sometimes
      showed ongrowth of fibrous tissue derived from the recipient's aorta. Grafts
      potentially viable at implantation showed three main patterns of fibroblastic
      growth: (1) relatively sparse, scattered cells; (2) focal hyperplastic growth
      with intervening acellular tissue that was prone to rupture; and (3) widely
      disseminated, vigorous growth causing abnormal thickening. The first pattern was
      associated with recipient cells, and both the second and third patterns were
      associated with nonrecipient cells. CONCLUSIONS: Donor cells surviving
      implantation do not maintain a normal leaflet architecture and may lead to
      failure by producing loss of leaflet flexibility.

PMID- 9930456
TI  - Assessment of glutaraldehyde crosslinking efficiency with an amine-specific
      fluorescent probe.
AB  - BACKGROUND: Crosslinking of heart valves with glutaraldehyde involves the binding
      of amine groups. We have developed a technique that provides an inverse measure
      of the degree of tissue fixation by quantifying the amount of unbound amines.
      METHODS: Whole aortic valves were exposed to 0.5% glutaraldehyde solution for 0,
      1, 15, and 60 minutes, 6 hours, and 1 and 7 days. Frozen sections were exposed to
      carboxyfluorescein succinimidyl ester, a fluorescent amine-reactive probe. Images
      were acquired from each section and processed to separate pixels representing
      tissue from those representing background. An average fluorescent intensity for
      each image was calculated and related to the number of unbound amines by
      comparing with standards. RESULTS: The amount of uncrosslinked amines was
      observed to decrease exponentially with fixation time and achieved a plateau at 1
      day of fixation. A significant difference in the amount of unbound amines also
      exists between valve leaflets fixed while connected to the root and those excised
      from the root before fixation. CONCLUSIONS: This amine measurement technique,
      being sensitive to spatially varying differences in chemical fixation, should be
      useful in evaluating the efficacy of new fixation protocols.

PMID- 9930457
TI  - Evaluation of porcine valves prepared by dye-mediated photooxidation.
AB  - BACKGROUND: Previous studies demonstrated that dye-mediated photooxidation can
      stabilize bovine pericardium. Here, photooxidized porcine valve cusp and root
      tissue were assessed in comparison to fresh and glutaraldehyde-treated samples.
      METHODS AND RESULTS: In an in vitro tissue solubility test, both photooxidized
      and glutaraldehyde-treated tissues were resistant to protein extraction compared
      to fresh tissue. A rat subcutaneous model was used to test in vivo stability and
      calcification potential. In this study, four of the six fresh leaflets were not
      visible because of resorption while both photooxidized and glutaraldehyde-treated
      tissues were biostable. Mineral contents of the rat explants were much lower for
      both fresh and photooxidized leaflets when compared with glutaraldehyde-treated
      leaflets. Also, the aortic root calcified whether treated or not with the most
      mineral being associated with glutaraldehyde-treated root. Analysis of
      photooxidized porcine valves explanted from the mitral position in sheep
      indicated a material that was biostable and contained only minor calcification,
      perhaps due to deformed stents. CONCLUSIONS: Porcine valve tissue treated by dye
      mediated photooxidation is biostable and resistant to calcification, and has
      potential for use in heart valve bioprostheses.

PMID- 9930458
TI  - Comparison of different anticalcification treatments for stentless bioprostheses.
AB  - BACKGROUND: New anticalcificant treatments have been developed because tissue
      calcification is a major contributing factor for bioprosthetic valve failure.
      METHODS: Aortic valve leaflet and aortic root tissue samples from stentless
      bioprostheses treated with No-React (Biocor, Belo Horizonte, Brazil), AOA
      (Medtronic freestyle, Minneapolis, MN), and BiLinx (St. Jude Medical, St. Paul,
      MN) were compared to a control group by subcutaneous implantation in 60 male
      weanling Sprague-Dawley rats. RESULTS: Calcium levels were in the range of 0.3 to
      2.2 mg/g dry tissue at 3 and 12 weeks in all three treated aortic valve leaflet
      implants. The BiLinx treatment proved anticalcificant effectiveness on aortic
      root samples as well. There were statistically significant differences for valve
      leaflet tissue samples: No-React = AOA < BiLinx < < Control and for aortic root
      tissue samples: BiLinx < < AOA < Control = No-React. CONCLUSION: Calcification of
      aortic valve leaflets was significantly reduced by all new anticalcificant
      treatments. Inhibition of cellular calcification (BiLinx) resulted in additional
      reduction of aortic root calcification. Maximum anticalcificant properties upon
      both leaflet and aortic root is important as these are considered a functional
      unit in stentless bioprostheses.

PMID- 9930459
TI  - Does glutaraldehyde induce calcification of bioprosthetic tissues?
AB  - BACKGROUND: Glutaraldehyde has been said to be responsible in part for the
      calcification of glutaraldehyde-treated tissues after implantation in animals or
      humans. We investigated whether the origin of the tissue, autologous or
      heterologous, could have a more prominent role in the process of calcification.
      METHODS: Three-month-old sheep received sheep pericardial samples (n = 133) and
      human pericardial samples (n = 123) implanted subcutaneously. Samples were
      treated with 0.6% glutaraldehyde for 5, 10, or 20 minutes or 7 days and then
      rinsed thoroughly before implantation. Samples were then retrieved after 3
      months. Calcium content was assessed by spectrophometry. RESULTS: The results
      show a low calcium content in the autologous group (mean 1.14+/-2.07) and a high
      calcium content in the heterologous group (mean 38.97+/-26). These results were
      the same regardless of the duration of the treatment. CONCLUSIONS: Glutaraldehyde
      treatment (0.6%) does not play a significant role in the calcification of
      glutaraldehyde-treated tissue regardless of the origin, autologous or
      heterologous, of the tissue. Glutaraldehyde-treated autologous tissues are
      associated with an incidence of calcification lower than heterologous tissues.

PMID- 9930460
TI  - Early clinical experience with the Tissuemed porcine bioprosthesis.
AB  - BACKGROUND: Tissuemed (Leeds, England) porcine bioprostheses are freshly mounted
      and dilated for correct functional sizing and commissural alignment, then fixed
      under low pressure. These valves closely approximate the natural leaflet
      geometry, reduce opening commissural bending stresses, and may provide a solution
      to structural valve failure from calcification and tears. To evaluate the
      performance of the bioprosthesis 207 Tissuemed bioprostheses were implanted in
      203 patients, 114 men and 89 women (mean age 73 years; range 56 to 94 years),
      between 1991 and 1996. Preoperatively 66% of the patients were in New York Heart
      Association functional class III or IV. There were 175 aortic, 22 mitral, 2
      tricuspid, and 4 multiple replacements. Concomitant procedures were performed in
      26.1% (53 of 203) of patients. Follow-up was 99.5% (total cumulative follow-up
      447.5 patient-years). RESULTS: The 30 day mortality, influenced by age and valve
      position, was 11.8% with no early valve-related deaths. Patient survival at 5
      years was 76% (standard error 3.3%). Valve-related complication rates (expressed
      as percent per patient-year and number of events) were thromboembolism 1.1% (5),
      hemorrhage 0.7% (3), bacterial endocarditis 0.2% (1), nonstructural valve failure
      0.2% (1), and reoperation 0.5% (2). At 5 years freedom from valve-related events
      were as follows: thromboembolism 92.9% (standard error 2.7%), hemorrhage 96.1%
      (standard error 1.9%), endocarditis 98.1% (standard error 1.8%), nonstructural
      valve failure 99.2% (standard error 0.7%), structural valve dysfunction 100%
      (standard error 0.0%), and reoperation 98.1% (standard error 1.8%). At follow-up
      73.8% of the patients were in New York Heart Association functional class I or
      II. CONCLUSIONS: There were no early valve-related deaths, no episodes of
      structural valve failure, and valve-related complications compared favorably with
      other porcine series. There was overall clinical improvement in patient symptoms.
      Our experience suggests that the Tissuemed porcine bioprosthesis is a safe and
      reliable heart valve providing good clinical improvement in patient symptoms.
      Long-term clinical follow-up is, however, essential to complete the evaluation.

PMID- 9930461
TI  - Heat treatment mitigates calcification of valvular bioprostheses.
AB  - BACKGROUND: Several techniques have been proposed to mitigate calcification of
      glutaraldehyde-preserved bioprostheses. None has been fully satisfactory. Knowing
      that heat induces significant molecular changes, we investigated the potential
      benefit of the heat treatment of glutaraldehyde-fixed tissues. METHODS: Samples
      of porcine valves and bovine pericardium treated in 0.625% glutaraldehyde were
      submitted to temperatures from 37 degrees to 70 degrees C for 2 to 12 weeks and
      then implanted subcutaneously in newborn rats for 3 months. In a second protocol,
      nine heat-treated porcine valve bioprostheses and seven control porcine valve
      bioprostheses were implanted in the mitral position in sheep for 20 weeks.
      RESULTS: Spectrophotometry and x-ray analysis comparing heat-treated versus non
      heat-treated tissues showed the following: porcine valve: 6.7+/-2.3 microg Ca/mg
      (n = 8) versus 239.9+/-2.9 /g Ca/mg (n = 8); bovine pericardium: 19.5+/-8 microg
      Ca/mg (n = 6) versus 108+/-10.3 microg Ca/mg (n = 8); and porcine valve
      bioprostheses: 0 versus ++. CONCLUSIONS: Heat treatment of glutaraldehyde-treated
      bioprostheses significantly mitigated calcification in both subcutaneous and
      mitral position.

PMID- 9930462
TI  - Mammary side branch steal: is this a real or even clinically important
      phenomenon?

PMID- 9930463
TI  - Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision
      analysis.
AB  - BACKGROUND: Preliminary studies have shown that thoracic positron emission
      tomography (PET) is more accurate than thoracic computed tomography (CT) for the
      staging of non-small cell lung carcinoma. In the present study the cost
      effectiveness, as measured by national Medicare reimbursed costs, and patient
      life expectancy are used to compare several thoracic PET-based strategies with a
      conventional thoracic CT-based strategy for preoperative staging. METHODS: Five
      decision strategies for selection of potential surgical candidates were compared;
      thoracic CT alone or four different strategies that use thoracic CT plus thoracic
      PET. The various paths of each strategy are dependent on numerous variables that
      were determined from a review of the medical literature. Life expectancy was
      calculated using the declining exponential approximation of life expectancy and
      reduced on the basis of procedural morbidity and mortality. Costs were based on
      national Medicare reimbursed costs. For all possible outcomes of each strategy,
      the expected cost and projected life expectancy were determined. The effects of
      changing one or more variables on the expected cost and life expectancy were
      studied using sensitivity analysis. RESULTS: A strategy that uses PET only after
      a negative CT study is shown to be a cost-effective alternative to the CT-alone
      strategy ($25,286 per life-year saved). CONCLUSIONS: These results show through
      rigorous decision tree analysis the potential cost-effectiveness of using
      thoracic PET in the management of non-small cell lung carcinoma. Greater use of
      thoracic PET for nonsmall cell lung carcinoma staging is warranted, and further
      clinical trials should help to validate the analytic results predicted from this
      study.

PMID- 9930464
TI  - Success of laparoscopic fundoplication for gastroesophageal reflux disease.
AB  - BACKGROUND: We explored the efficacy of laparoscopic fundoplication (LF) in
      patients with uncomplicated, medically recalcitrant pathologic gastroesophageal
      reflux disease (GERD) for whom we previously would have recommended open surgical
      repair. METHODS: From January 1994 to January 1998, we performed LF on 150
      patients (80 men and 70 women) with GERD recalcitrant to maximal medical therapy.
      No patient suffered from esophageal stricture or epithelial dysplasia; however
      16% (24 of 150) had benign Barrett's mucosa. Preoperative esophageal manometry
      and 24-hour pH testing were obtained in 93% (139 of 150) and 89% (134 of 150) of
      patients, respectively. Nissen LF (n = 123), Toupet LF (n = 26), or Dor LF (n =
      1) were accomplished over a large (54 F) intraesophageal bougie. Preoperative (1
      month) and postoperative (>6 month) symptom scoring were assessed on a 0 to 10
      scale. Thirty-eight patients with a greater than 6-month postoperative period had
      manometry and pH studies performed. RESULTS: The laparoscopic approach was
      successful in 99% (148 of 150) of patients, and there has been no mortality.
      Operative time was 160+/-59 minutes. Open conversion was required for 2 patients:
      because of difficulty with dissection owing to adhesions in 1 case and due to
      perforation in another. Reoperation was required for 5 patients (1
      paraesophageal, 2 dysphagia, 2 recurrent reflux). Major postoperative
      complications involved stroke and pancreatitis in 1 patient each. Mean hospital
      stay was 2.6+/-1.2 days, full activity resumed by 7 days. Postoperative
      esophageal pH testing among 38 patients tested more than 6 months after operation
      demonstrated normal esophageal acid exposure in all but 2. GERD symptoms were
      relieved at 1 month, 6 months, and after 1 year in 95% (128 of 135), 94% (99 of
      105), and 93% (65 of 70) of patients, respectively. CONCLUSIONS: Intermediate
      term results with LF suggest this to be a reasonable approach to surgical
      management of medically recalcitrant uncomplicated GERD. Thoracic surgeons
      interested in GERD should become familiar with minimally invasive surgical
      approaches.

PMID- 9930465
TI  - Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary
      resection.
AB  - BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after
      pulmonary resection is usually a lethal complication. The etiology of this
      serious complication remains unknown despite many theories. Intubation,
      aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of
      treatment. Mortality rates from ARDS after pneumonectomy have been reported as
      high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available.
      We instituted an aggressive program to treat patients with ARDS after pulmonary
      resection. Patients were intubated and treated with standard supportive measures
      plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all
      patients had postural changes to improve ventilation/perfusion matching and
      management of secretions. Systemic steroids were given to half of the patients.
      RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS
      (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of
      arterial oxygen to the fraction of inspired oxygen at initiation of treatment was
      95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/
      8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours.
      Chest x-rays improved in all patients and normalized in 8. No adverse reactions
      to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment
      regimen for this lethal complication: intubation at the first radiographic sign
      of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per
      million); aspiration bronchoscopy and postural changes to improve management of
      secretions and ventilation/perfusion matching; diuresis and antibiotics; and
      consideration of the addition of intravenous steroid therapy.

PMID- 9930466
TI  - Is lobectomy by video-assisted thoracic surgery an adequate cancer operation?
AB  - BACKGROUND: Although the public perceives video-assisted thoracic surgery (VATS)
      as advantageous because it is less invasive than a thoracotomy, the medical
      community has questioned the safety of VATS lobectomy and its adequacy as a
      cancer operation. Reported series have not been able to address these issues
      because follow-up has been only short-term. METHODS: A multiinstitutional,
      retrospective review was performed in 298 consecutive patients who underwent VATS
      for a standard anatomic lobectomy with lymph node dissection for lung cancer.
      Pathologic staging was I in 233 (78%), II in 27 (9%), and IIIA in 38 (13%)
      patients. Kaplan Meier survival analysis was performed. RESULTS: The conversion
      rate from VATS lobectomy to thoracotomy was 6%, but none were for massive
      intraoperative bleeding. The only death (0.3%) was because of mesenteric venous
      thrombosis. Forty minor complications occurred in 38 patients (12.8%) undergoing
      VATS. The mean and median lengths of stay were 5+/-3.39 and 4 days, respectively.
      Recurrence in an incision occurred in 1 patient (0.3%). The Kaplan Meier 4-year
      survival for stage I was 70%+/-5%. CONCLUSION: The VATS lobectomy for
      bronchogenic carcinoma appears to be a safe operation, with the same survival as
      expected for a lobectomy done by thoracotomy.

PMID- 9930467
TI  - Short-course induction chemoradiotherapy with paclitaxel for stage III non-small
      cell lung cancer.
AB  - BACKGROUND: This study assessed toxicity, tumor response, disease control, and
      survival after short-course induction chemoradiotherapy and surgical resection in
      patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five
      patients with stage III non-small-cell lung carcinoma received 12-day induction
      therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour
      infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation
      radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was
      scheduled for 4 weeks later. Postoperatively, a second identical course of
      chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS:
      Induction toxicity resulted in hospitalization of 18 (40%) patients for
      neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who
      underwent thoracotomy, resection for cure was possible in 32 (71%) patients.
      Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged
      to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19
      months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were
      from recurrent disease, three were from treatment, and two were unrelated.
      Recurrent disease was distant in 21 patients, distant and locoregional in 2, and
      locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected
      24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for
      pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged
      patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63%
      for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS:
      We conclude that short-course neoadjuvant therapy with paclitaxel (1) has
      manageable toxicity and a low treatment mortality, (2) results in good tumor
      response and downstaging, (3) provides excellent locoregional control with most
      recurrences being distant, and (4) has improved the median survival compared with
      historical controls. Survival was better in stage IIIA patients, resectable
      patients, pathologic responders, and patients downstaged to mediastinal node
      negative disease (stage 0, I, or II).

PMID- 9930468
TI  - The clinical significance of hepatocyte growth factor for non-small cell lung
      cancer.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that is released after
      injury. It is a paracrine factor that is produced by mesenchymal cells;
      epithelial and endothelial cells respond to HGF through its receptor, the c-met
      protein. Hepatocyte growth factor induces cell growth and cell movement and is
      also highly angiogenic. Evidence from breast cancer patients suggests that HGF is
      a negative prognostic indicator for breast cancer and is associated with invasive
      disease. METHODS: We measured the HGF content in tumor tissue from 56 non-small
      cell lung cancer patients using the Western blot technique. The amount of HGF in
      tumor extracts was quantitated by densitometry after transfer of proteins to
      nitrocellulose and exposure to antibodies. Survival curves were generated based
      on clinical information obtained for each patient. RESULTS: Our data indicate
      that HGF is also a negative prognostic indicator in lung cancer. As in the study
      of breast cancer patients, HGF was associated with recurrence and poor survival;
      the relative risk was seen to increase with increasing HGF tumor content. At
      levels of HGF greater than 100 units, the relative risk was 10, compared with
      that in patients with an HGF level of 1 unit. Node-negative patients with an
      elevated HGF tumor content had a significantly poorer outcome than node-positive
      patients with a low HGF tumor content. The same relationship was observed if the
      patients were stratified by stage: elevated HGF was associated with stage I
      patients whose disease recurred and who died of their disease, and stage I
      patients with elevated HGF had a worse survival than higher stage patients with a
      low level of HGF. CONCLUSIONS: These results suggest that elevated HGF may
      predict a more aggressive biology in non-small cell lung cancer patients. The
      level of HGF may be useful as an indicator of high risk in early stage lung
      cancer patients.

PMID- 9930469
TI  - Operation for chronic pulmonary thromboembolism accompanied by thrombophilia in 8
      patients.
AB  - BACKGROUND: Medical therapy for chronic pulmonary thromboembolism is limited, and
      surgical treatment has become more frequent recently. We have performed pulmonary
      thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism
      accompanied by thrombophilia. METHODS: The patients were 6 men and 2 women aged
      21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2
      had protein C deficiency, and 1 had congenital antithrombin III deficiency. The
      preoperative condition was New York Heart Association functional class III in 5
      and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary
      artery pressure, 47+/-6.7 mm Hg), and low cardiac output were observed in all
      patients. After a median sternotomy, deep hypothermia was induced using a
      cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral
      pulmonary arteries was performed under intermittent circulatory arrest. RESULTS:
      There were no operative deaths. Long-term respiratory management was needed
      postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury
      was observed. The arterial blood oxygen concentration improved, and the mean
      pulmonary pressure decreased to 16+/-5.5 mm Hg. The cardiac output also
      increased, and New York Heart Association functional class improved to I in 4 and
      II in 4 patients. CONCLUSION: Pulmonary thromboendarterectomy under deep
      hypothermic intermittent circulatory arrest was effective for chronic pulmonary
      thromboembolism accompanied by thrombophilia for which medical treatment is of
      limited value.

PMID- 9930470
TI  - Stenting for airway obstruction in the carinal region.
AB  - BACKGROUND: Recent progress on airway stents has provided sufficient airway
      patency for patients with airway obstruction; however, when the stenosis exists
      in the carinal zone, establishing an excellent airway condition is still
      troublesome because of the anatomic structure. METHODS: We treated 15 patients
      with severe tracheobronchial stenosis involving a carinal bifurcation region,
      using several types of stenting devices (long T-tube, T-Y tube, wire reinforced Y
      tracheostomal tube, Freitag Dynamic stent [Karl Storz, Tuttlingen, Germany], and
      covered metallic stent). All patients had advanced inoperable tumors (lung
      cancer, n = 6; esophageal cancer, n = 3; thyroid cancer, n = 3; mediastinal
      tumor, n = 3). RESULTS: All but 2 patients had immediate relief of respiratory
      symptoms. One patient died of respiratory failure caused by pulmonary lymphatic
      spread 3 days after Dynamic stent insertion. In 1 patient with severe left main
      bronchial stenosis due to lung cancer, effective palliation was not achieved by
      insertion of a covered metallic stent because of its insufficient expansion
      against the stenosis. Mean survival after successful stenting was 4.3 months
      (range, 1 to 15 months). There were no complications directly attributable to the
      stents. CONCLUSIONS: As evidenced by the clinical effectiveness, airway stenting
      for inoperable tumor is valuable in such patients. Choosing a stent that will
      fully cover the lesion and allow sufficient tolerance against compression is
      important to successful stenting. Benefits such as ease of phonation and stent
      maintenance should also be considered.

PMID- 9930471
TI  - Pneumonectomy for lung metastases: indications, risks, and outcome.
AB  - BACKGROUND: Resection of pulmonary metastases (PM) by pneumonectomy is
      infrequently performed and benefits are uncertain. METHODS: From 1985 to 1995, 42
      patients underwent pneumonectomy for PM. Twenty-nine patients had PM from
      sarcomas, 12 patients from carcinomas, and 1 patient from melanoma. The
      indications for pneumonectomy were pulmonary recurrences in 12 patients, PM
      centrally located in 26 patients, and high number of PM in 4 patients. There were
      11 intrapericardial and 6 extended pneumonectomies. The average number of PM
      resected was 3. Twenty-two patients (52%) had lymph nodes involvement. RESULTS:
      There were 2 postoperative deaths (4.8%) related to pneumonectomy and one death
      within 30 days for rapidly evolving disease; 4 patients (9.5%) had major
      postoperative complications that were medically treated. Five patients (12%) were
      operated on for recurrences on the residual lung. At the completion of the study,
      12 patients were still alive, 8 without recurrences. The median survival was 6.5
      months (range, 1 to 144 months); the 5-year survival was 16.8%. CONCLUSIONS:
      Pneumonectomy should not be considered an absolute contraindication in patients
      with PM, but the poor outcome of our series suggests strict criteria of
      selection.

PMID- 9930472
TI  - Donor cardiac troponin T: a marker to predict heart transplant rejection.
AB  - BACKGROUND: Noninvasive methodologies have shown poor sensitivity in predicting
      rejection when compared to serial endomyocardial biopsies. We studied the
      potential role of donor blood troponin T (Tn-T) as a marker for predicting heart
      transplant rejection. METHODS: Blood cardiac Tn-T was measured from 16 heart
      donors. Transplant rejection and cardiac function in the recipients were
      monitored for 1 year. RESULTS: When data were analyzed based on donor blood Tn-T
      levels, 6 patients who received hearts from donors with low Tn-T (<0.45+/-0.1
      ng/mL) showed no rejection, and patients whose hearts came from donors with
      higher Tn-T (6.01+/-0.81 ng/mL) developed episodes of high-grade rejection (3A)
      within 38.5+/-2.1 days after transplantation. Eight patients who received hearts
      from donors with intermediate levels of Tn-T (3.57+/-0.55 ng/mL) showed mild
      rejection (grade 1). All recipients had qualitatively normal left ventricular
      systolic function by serial echocardiography. The mean donor ischemic time was
      169+/-47 minutes. CONCLUSIONS: The quality of the donor heart is an important
      prognostic factor in heart transplantation. It may be possible to identify
      severely damaged donor organs before transplantation and avoid their use or to
      develop more aggressive strategies for reducing recurrent acute rejection
      episodes in high-risk patients.

PMID- 9930473
TI  - Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing
      mechanical and biological prostheses.
AB  - BACKGROUND: Little is known of time-related outcome and comparative performance
      of biological and mechanical prostheses following tricuspid valve replacement
      (TVR). METHODS: A retrospective UK Heart Valve Registry study (Jan 1, 1986 to
      June 30, 1997) identified 425 patients who underwent TVR. Two-hundred twenty-five
      (52.9%) received biological and 200 (47.1%) received mechanical valves. One
      hundred sixty (38%), 158, and 76 had isolated, double, and triple valve
      replacements, respectively. The follow-up was 96% complete with a total of 1,585
      patient-years. RESULTS: Thirty-day mortality for TVR was 17.3% (73 deaths). One-,
      5-, and 10-year survival rates were 72.2%, 59.9%, and 42.9%, respectively. Year
      of operation (p = 0.04), age (p = 0.04), and number of valves implanted (p = 0.0
      3) predicted overall mortality. Age (p<0.001) and year of operation (p = 0.002)
      predicted overall survival. Thirty-day mortality for biological and mechanical
      prostheses was 18.8% and 15.6%, respectively. One-, 5-, and 10-year survival
      rates were 70.5%, 61.5%, and 47.7% for biological and 74.0%, 57.9%, and 33.9% for
      mechanical prostheses, respectively. Freedom from reoperation at 1 and 10 years
      was 98.7% and 97.4%. Freedom from death or reoperation was 71.2% at 1 year and
      41.9% at 10 years. None of the above outcomes was significantly different between
      the type of valve prostheses. CONCLUSIONS: TVR carries a high 30-day mortality
      and a poor longer term survival. No superiority could be identified for
      biological or mechanical prostheses in the tricuspid position for either survival
      or reoperation.

PMID- 9930475
TI  - Preconditioning prevents myocardial stunning after cardiac transplantation.
AB  - BACKGROUND: Preconditioning has been shown to reduce myocardial stunning after
      reversible global ischemia. To determine whether preconditioning improves
      functional recovery after cardiac transplantation, 16 sheep were randomly
      assigned to a preconditioning protocol or to a control group. METHODS:
      Preconditioning was achieved with 5 minutes of global ischemia followed by 10
      minutes of reperfusion. The heart was then arrested with 1 L of crystalloid
      cardioplegia, explanted, stored in a transport cooler, and then transplanted into
      recipient sheep. The total ischemia time was 2 hours. Pressure-volume loops were
      used to calculate preload recruitable stroke work, the maximum elastance, and
      diastolic compliance. Linear regression analysis was used to determine the
      preload recruitable stroke work, maximum elastance, and diastolic compliance-and
      end-diastolic volume relationship. The area under the regression curve for
      preload recruitable stroke work was defined as the preload recruitable stroke
      work area. Biopsies were taken for high-energy phosphates. RESULTS: Systolic
      function, represented by preload recruitable stroke work area, was preserved
      after cardiac transplantation in preconditioned animals. Maximum elastance and
      diastolic compliance were unaffected by preconditioning or ischemia. High-energy
      phosphates were better preserved in preconditioned animals. CONCLUSION:
      Preconditioning prevented myocardial stunning and preserved high-energy
      phosphates after experimental cardiac transplantation.

PMID- 9930474
TI  - Sustained reduction of neointima with c-myc antisense oligonucleotides in
      saphenous vein grafts.
AB  - BACKGROUND: Treatment of saphenous veins with c-myc antisense oligomers during
      preparation for grafting reduces medial cellular proliferation and macrophage
      infiltration, and preserves medial smooth muscle content at 3 days. Accordingly,
      the purpose of this study was to examine whether c-myc antisense oligomers have
      an impact on late vein graft remodeling. METHODS: Sixty-two pigs underwent
      unilateral saphenous vein-carotid artery interposition grafting. Harvested veins
      were incubated either in saline (control group) or 20-micromol/L or 200
      micromol/L concentrations of c-myc antisense oligomers (treated groups) for 30
      minutes intraoperatively. Three months after surgery, vein graft histology was
      assessed. RESULTS: Forty-five of 62 randomized animals survived the experiment;
      no differences in animal survival or graft patency among the groups were observed
      (p = NS, chi2). C-myc antisense oligomers significantly decreased neointimal and
      wall thickness, as well as increased lumenal index, in treated groups (p<0.04,
      p<0.03, and p<0.001, respectively, analysis of variance). In contrast, there was
      no difference in medial thickness or perivascular wound healing. CONCLUSION:
      Intraoperative treatment of saphenous veins with c-myc antisense oligomers
      decreased neointimal formation at 3 months after grafting. In conjunction with
      our previous reports, these findings suggest that early inhibition of cellular
      proliferation and inflammatory infiltration results in a sustained reduction in
      neointimal formation and favorable graft remodeling.

PMID- 9930476
TI  - Serum S100beta release after coronary artery bypass grafting: roller versus
      centrifugal pump.
AB  - BACKGROUND: Microemboli generated during cardiopulmonary bypass (CPB) are
      implicated in the cerebral injury seen after coronary artery bypass grafting.
      Centrifugal pumps generate fewer microemboli than roller pumps. Increased
      S100beta levels have been reported after coronary artery bypass grafting, with
      levels greater than 1 ng/mL resulting in poorer neuropsychologic outcome. This
      study investigated the potential neurologic benefits of centrifugal pumps, by
      using S100beta as a marker for cerebral injury. METHODS: Thirty-two patients who
      had coronary artery bypass grafting were randomly assigned to two groups. Serial
      blood samples (preoperative, end of bypass, 30 minutes, and 2 and 24 hours after
      cardiopulmonary bypass) were taken and the serum analyzed for S100beta using a
      new immunoluminometric assay. RESULTS: Both groups were matched for age, number
      of grafts, and cardiopulmonary bypass and cross-clamp times. Postoperative serum
      S100beta levels were significantly higher in both groups than preoperative
      levels. Peak S100beta levels did not correlate with cardiopulmonary bypass time;
      however, 24-hour S100beta levels correlated with intubation time r = 0.40, p =
      0.04). Th ere was no significant difference in S100beta levels between the groups
      at any of the time points. CONCLUSIONS: S100beta levels increased after coronary
      artery bypass grafting. Centrifugal pumps do not significantly decrease S100beta
      release. Persistently increased S100beta levels are associated with longer
      intubation times.

PMID- 9930477
TI  - Partial left ventriculectomy for idiopathic dilated cardiomyopathy: early results
      and six-month follow-up.
AB  - BACKGROUND: Recent reports show that partial left ventriculectomy improves
      hemodynamic and functional status in patients with dilated cardiomyopathy. This
      study sought to determine the effects of partial left ventriculectomy on clinical
      outcome and left ventricular function during 6-month follow-up. METHODS: Twenty
      two patients underwent partial left ventriculectomy. Mitral valve repair was
      performed whenever possible, otherwise the valve was replaced. Hemodynamic and
      functional data were obtained at baseline, as well as 2 weeks and 6 months
      postoperatively. RESULTS: Overall, 7 of 22 patients died; there were three early
      and four late deaths. One-year survival was 68%+/-10%. Ejection fraction
      increased from 23.9%+/-6.8% before the operation to 40.7%+/-12.5% at 2 weeks and
      to 36.8%+/-7.7% at 6 months (p<0.001, for both). The cardiac index before the
      operation, at 2 weeks, and at 6 months was 2.3+/-0.8, 2.9+/-0.6, and 3.4+/-1.0
      L/m2 per minute, respectively (p = 0.035, and p = 0.009, compared with baseline).
      The increase in ejection fraction 2 weeks postoperatively was less in patients
      with left circumflex artery dominance (10.9%+/-3.2% compared with 19.9%+/-10.7%,
      respectively, p = 0.017). At 6-month follow up, all surviving patients except one
      improved New York Heart Association functional class when compared with
      preoperative status (from 3.8+/-0.4 to 1.4+/-0.6, p = 0.0002). CONCLUSIONS: Early
      hemodynamic improvement after partial left ventriculectomy was maintained during
      midterm follow-up.

PMID- 9930478
TI  - What is the marginal cost for marginal risk in cardiac surgery?
AB  - BACKGROUND: It has been shown that postoperative length of stay (LOS) correlates
      highly with mortality risk for cardiac surgical procedures. Similar correlations
      have been found for charges with LOS and costs with risk. METHODS: Postoperative
      LOS and risk scores were obtained, tabulated, and compiled into the five original
      Parsonnet risk groups for 2,589 patients who underwent cardiac operations from
      1992 through 1996 at one hospital. The correlation of the group mean LOS with the
      group mean risk was tested. RESULTS: The correlation coefficient was 0.9827;
      96.58% of the variance was removed using risk to predict LOS. A calculation of
      the difference in cost for difference in risk for cohorts of patients is
      developed. CONCLUSIONS: The high correlation of mean LOS with mean risk permits
      calculation of marginal cost for marginal risk based on clinical data. The
      marginal cost is equal to the difference in variable costs for cohorts.

PMID- 9930479
TI  - Comparison of the morphologic and vascular reactivity of the proximal and distal
      radial artery.
AB  - BACKGROUND: Variations in the morphology and vascular reactivity of the proximal
      and distal radial artery might influence its performance as a bypass conduit.
      METHODS: The morphologic and functional characteristics of the proximal and
      distal RAs were compared with those of the left and right internal mammary
      arteries by using histologic and in vitro organ bath techniques. RESULTS:
      Proximal RA had a significantly greater medial cross-sectional area compared with
      that of the distal RA (2.48+/-0.27 mm2 compared with 1.86+/-0.21 mm2, p< 0.05),
      which were both significantly greater than the left internal mammary artery
      (0.54+/-0.09 mm2) or the right internal mammary artery (0.67+/-0.03 mm2).
      Proximal RA had a significantly greater response to 90 mmol/L potassium chloride
      than that of distal RA (88.4+/-7.3 compared with 60.2+/-10.3 mN, p<0.05), and
      both contracted more than the left internal mammary artery (30.3+/-2.9 mN) and
      the right internal mammary artery (32.6+/-4.1 mN). There was no difference in the
      response to noradrenaline and adrenaline between proximal and distal RA, both of
      which contracted more than the left and right internal mammary arteries.
      CONCLUSIONS: When choosing a segment of RA for use as a bypass conduit, regional
      variations in biologic properties should be considered.

PMID- 9930480
TI  - Intraoperative angiography to assess graft patency after minimally invasive
      coronary bypass.
AB  - BACKGROUND: Intraoperative angiography was performed to confirm graft patency
      immediately after minimally invasive coronary bypass operations. METHODS: In 26
      patients who had internal mammary artery grafting, intraoperative coronary
      angiography was performed with a portable digital fluoroscope. RESULTS: High
      resolution angiograms were obtained in all cases. Angiography documented
      vasospasm of the graft or native vessel in 9 patients (graft in 3, native in 2,
      graft and native in 4 others), which responded promptly to intracoronary
      vasodilators in all. Angiography identified technically unsuspected and
      clinically silent fixed stenoses (>50%) in 11 patients, attributable to graft
      kinking in 2, anastomotic obstruction in 6 (total occlusion in 4), and stenosis
      of the left anterior descending artery just distal to the anastomosis in three
      cases (total occlusion in one). In 9 of 11 patients, fixed stenoses were
      sufficiently severe to warrant intraoperative intervention by surgical revision
      (n = 5) or angioplasty via the graft (n = 4). CONCLUSIONS: Intraoperative
      angiography after minimally invasive coronary artery bypass operations can
      immediately identify dynamic and fixed obstructions and facilitate their prompt
      treatment, thereby ensuring that each patient leaves the operating room with an
      optimal surgical result.

PMID- 9930481
TI  - Activity-rest stimulation of latissimus dorsi for cardiomyoplasty: 1-year results
      in sheep.
AB  - BACKGROUND: In dynamic cardiomyoplasty electro-stimulation achieves full
      transformation of the latissimus dorsi (LD); therefore, its slowness limits the
      systolic support. Daily activity-rest could maintain partial transformation of
      the LD. METHODS: Sheep LD were burst-stimulated either 10 or 24 hours/day. Before
      and 2, 4, 6, and 12 months after stimulation, LD power output, fatigue
      resistance, and tetanic fusion frequency were assessed. Latissimus dorsi were
      biopsied at 6 months, and sheep sacrificed at 12 months. RESULTS: After 1 year of
      10 hours/day stimulation LD was substantially conserved and contained large
      amounts of fast type myosin. From 2 months to 1 year of stimulation the power per
      muscle of the daily rested LD was greater than that of the left ventricle, being
      three to four times higher than in the 24-hour/day stimulation. CONCLUSIONS: If
      extended to humans, these results could be the rationale for the need of a
      cardiomyostimulator, whose discontinuous activity could offer to patients the
      long-standing advantage of a faster and powerful muscle contraction.

PMID- 9930482
TI  - Heat shock improves recovery and provides protection against global ischemia
      after hypothermic storage.
AB  - BACKGROUND: Improved methods of donor heart preparation before preservation could
      allow for prolonged storage and permit remote procurement of these organs.
      Previous studies have shown that overexpression of heat-shock protein 72 provides
      protection against ischemic cardiac damage. We sought to determine whether rats
      subjected to heat stress with only 6-hour recovery could acquire protection to a
      subsequent heart storage for 12 hours at 4 degrees C. METHODS: Three groups of
      animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats
      (whole-body hyperthermia 42 degrees C for 15 minutes). After 12-hour cold
      ischemia hearts were reperfused on a Langendorff column. To confirm any
      differences in functional recovery, hearts were then subjected to an additional
      15-minute period of warm global ischemia after which function and lactate
      dehydrogenase enzyme leakage were measured. RESULTS: Heat-shocked animals showed
      marked improvements compared with controls in left ventricular developed pressure
      (63+/-4 mm Hg versus 44+/-4 mm Hg, p<0.05) heart rate x developed pressure
      (13,883+/-1,174 beats per minute x mm Hg versus 8,492+/-1,564 beats per minute x
      mm Hg, p<0.05), rate of ventricular pressure increase (1,912+/-112 mm Hg/second
      versus 1,215+/-162 mm Hg/second, p<0.005), rate of ventricular pressure decrease
      (1,258+/-89 mm Hg/second versus 774+/-106 mm Hg/second, p<0.005). Diastolic
      compliance and lactate dehydrogenase release were improved in heatshocked animals
      compared with controls and sham-treated animals. Differences between heat-shocked
      animals and control or sham-treated animals were further increased after the
      additional 15-minute period of warm ischemia. Western blot experiments confirmed
      increased heat-shock protein 72 levels in heat-shocked animals (>threefold)
      compared with sham-treated animals and controls. CONCLUSIONS: Heat shock 6 hours
      before heart removal resulted in marked expression of heat-shock protein 72 and
      protected isolated rat hearts by increased functional recovery and decreased
      cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of
      heart preservation for transplantation. Protection was further confirmed after an
      additional 15-minute period of warm ischemia.

PMID- 9930484
TI  - Warm reperfusion and myocardial protection.
AB  - BACKGROUND: The aim of this study was to determine whether warm reperfusion
      improves myocardial protection with cardiac troponin I as the criteria for
      evaluating the adequacy of myocardial protection. METHODS: One hundred five
      patients undergoing first-time elective coronary bypass surgery were randomized
      to one of three cardioplegic strategies of either (1) cold crystalloid
      cardioplegia followed by warm reperfusion, (2) cold blood cardioplegia followed
      by warm reperfusion, or (3) cold blood cardioplegia with no reperfusion. RESULTS:
      The total amount of cardiac troponin I released tended to be higher in the cold
      blood cardioplegia with no reperfusion group (3.9+/-5.7 microg) than in the cold
      blood cardioplegia followed by warm reperfusion group (2.8+/-2.7 microg) or the
      cold crystalloid cardioplegia followed by warm reperfusion group (2.8+/-2.2
      microg), but not significantly so. Cardiac troponin I concentration did not
      differ for any sample in any of the three groups. CONCLUSIONS: Our study showed
      that the addition of warm reperfusion to cold blood cardioplegia offers no
      advantage in a low-risk patient group.

PMID- 9930483
TI  - Activation of the protein C system during cardiopulmonary bypass with and without
      aprotinin.
AB  - BACKGROUND: The protein C system is important in the regulation of hemostasis. We
      studied its behavior during coronary artery bypass grafting procedures with and
      without aprotinin treatment using assays sensitive for activation of the protein
      C system. METHODS: In a prospective, double-blind, randomized study of 48
      patients we investigated the levels of antigen to proteins C and S and of the
      complexes between activated protein C with its two major plasma inhibitors,
      protein C inhibitor and alpha1-antitrypsin in patients treated with placebo (n =
      17), low-dose (n = 15), and high-dose (n = 16) aprotinin during elective coronary
      artery bypass grafting. RESULTS: The levels of proteins C and S showed a rapid
      decrease after heparinization, decreased greatly after start of cardiopulmonary
      bypass, and remained stable during cardiopulmonary bypass. Activated protein C
      inhibitor complexes were markedly elevated at the start of the procedure.
      Activated protein C-alpha1-antitrypsin decreased greatly after the start of
      cardiopulmonary bypass and remained stable during cardiopulmonary bypass. A
      significant peak was observed at the intensive care unit. Activated protein C
      protein C inhibitor levels showed a peak after heparinization in accordance with
      the accelerating effect of heparin on the complex formation but decreased
      thereafter. Treatment with aprotinin did not notably alter any of the measured
      patterns. CONCLUSIONS: In this study no evidence was found for increased
      activation of the protein C system during coronary artery bypass grafting.
      Administration of aprotinin did not result in different patterns of activation of
      the protein C system.

PMID- 9930485
TI  - Selective convective brain cooling during hypothermic cardiopulmonary bypass in
      dogs.
AB  - BACKGROUND: Neurologic complications, primarily resulting from ischemic insults,
      represent the leading cause of morbidity and disability, and the second most
      common source of death, after cardiac operations. Previous studies have reported
      that increases (as occur during the rewarming phase of cardiopulmonary bypass
      [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can
      significantly worsen or improve, respectively, postischemic neurologic outcome.
      The purpose of the present study was to evaluate a novel approach of selectively
      cooling the brain during hypothermic CPB and subsequent rewarming. METHODS:
      Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled
      halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood
      pressure near 75 mm Hg were maintained. Temperatures were monitored by placing
      thermistors in the esophagus (i.e., core), parietal epidural space, and brain
      parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature
      was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38
      degrees C. Forced air pericranial cooling (air temperature of approximately 13
      degrees C) was initiated simultaneous with the onset of CPB, and maintained
      throughout the bypass period. Brain-to-core temperature gradients were calculated
      by subtracting the core temperature from regional brain temperatures. RESULTS: In
      halothane-anesthetized dogs, brain temperatures at all monitoring sites were
      significantly less than core during all phases of CPB, with one exception (2 cm
      during systemic cooling). Brain cooling was most prominent during and after
      systemic rewarming. For example, during systemic rewarming, average temperatures
      in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees
      +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6
      degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but
      of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For
      example, during systemic rewarming, corresponding brain temperatures were 6.5
      degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C
      cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain
      cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0
      degrees C change previously reported to modulate ischemic injury, and was most
      prominent during the latter phases of CPB. When compared with previous research
      from our laboratory, application of cold forced air to the cranial surface
      resulted in brain temperatures that were cooler than those observed during
      hypothermic CPB without pericranial cooling. On the basis of the assumption that
      similar beneficial brain temperature changes can be induced in humans, we
      speculate that selective convective brain cooling may enable clinicians to
      improve neurologic outcome after hypothermic CPB.

PMID- 9930487
TI  - Immunogenic human leukocyte antigen class II antigens on human cardiac valves
      induce specific alloantibodies.
AB  - BACKGROUND: The kinetics of panel reactive antibodies (PRA) and incidence of
      antibodies directed against human leukocyte antigen (HLA) class II were studied
      in patients who received a cryopreserved cardiac valve allograft. METHODS: A
      complement-dependent microlymphocytotoxicity test was used to determine the
      percentage of panel reactive antibodies. Anti-HLA class II antibodies were
      measured by two-color fluorescence assays. RESULTS: The panel reactive antibodies
      became positive in 25 (78%) of 32 recipients between 1 and 16 months after
      implantation. Antibodies against HLA class II antigens were detected in 11 (37%)
      of 30 patients. In 9 (82%) of 11 cases these antibodies were donor specific. The
      induction of antibodies against donor HLA class II antigens suggests that intact
      HLA class II antigens are expressed by viable cells within the graft.
      Dithiothreitol analysis showed that the antibodies were of the immunoglobulin G
      type. Apparently, the HLA class II antigens are expressed in an immunogenic way,
      as activation of specific T-helper cells is essential for the switch from
      immunoglobulin M to immunoglobulin G antibodies. CONCLUSIONS: Allogeneic valve
      transplantation is associated with the production of donor-specific anti-HLA
      class I and II antibodies that could contribute to graft failure. This possibly
      detrimental effect might be prevented by cross matching in sensitized patients.

PMID- 9930486
TI  - Nitroglycerine reduces neutrophil activation and acute damage in latissimus dorsi
      muscle grafts.
AB  - BACKGROUND: Damage to the latissimus dorsi muscle (LDM) may jeopardize a
      successful outcome to dynamic cardiomyoplasty. We and others have demonstrated
      muscle damage in LDM in various species including humans. Ischemia is now
      recognized to be an important contributory factor. We postulated that glyceryl
      trinitrate, a nitric oxide donor, might protect against ischemic endothelial
      dysfunction and so reduce resultant muscle damage. METHODS: In 20 adult rats the
      left LDM was mobilized on its thoracodorsal neurovascular pedicle and maintained
      as an orthotopic graft. Half of the animals received glycerol trinitrate
      intraoperatively and postoperatively for 24 hours. The other half served as
      untreated controls. Each group was further subdivided into two groups (n = 5 in
      each): animals in which the LDM was excised after 4 hours for myeloperoxidase
      studies, and animals in which the LDM was excised at 24 hours for analysis of
      muscle damage by histology and enzyme macrohistochemistry. Blood samples were
      taken at 24 hours for assay of plasma nitrite and nitrate as nitric oxide
      metabolites. RESULTS: Glycerol trinitrate-treated animals had higher plasma
      nitric oxide metabolite levels after 24 hours (after nitrate reductase treatment,
      total nitrite, 78.3+/-11.8 nmol/mL, mean +/- SEM) than controls (42.1+/-3.7 nmol/
      mL, p = 0.008). The proportion of viable LDM in glycerol trinitrate-treated
      animals was greater than in untreated animals, mainly in the middle and distal
      regions of the graft (middle region, 96.3%+/-0.5% versus 75.7%+/-4.1%, p<0.001;
      distal region, 94.4%+/-0.8% versus 40.9%+/-3.1%, p<0.001). Macrohistochemical
      findings correlated well with the histologic findings. Myeloperoxidase activity
      (U/g) was markedly lower in glycerol trinitrate-treated LDMs, mainly in the
      distal part of the graft (glycerol trinitrate versus control, 20.5+/-2.1 versus
      40.9+/-3.1 U/g, p<0.001). CONCLUSIONS: Glycerol trinitrate significantly reduced
      acute damage to the distal two-thirds of the mobilized LDM, possibly by modifying
      leukocyte activation and endothelial dysfunction associated with ischemic injury.

PMID- 9930488
TI  - Late tamponade with mechanical circulatory support.
AB  - BACKGROUND: Circulatory support with mechanical devices often leads to bleeding
      and tamponade. METHODS: We report a series of three patients that required
      mechanical circulatory support for postcardiotomy ventricular dysfunction.
      RESULTS: Late tamponade occurred in each patient with different clinical
      presentations. Early postoperative bleeding occurred in 2 patients. There was no
      active bleeding in any of the 3 patients. Transesophageal echocardiography was
      not helpful in making the diagnosis. CONCLUSION: Late tamponade, which may be the
      result of hematoma with earlier bleeding, can present as dyspnea, hypoxia, or
      forms of hemodynamic collapse. Exploratory media sternotomy is required to
      definitively make the diagnosis and to evacuate the hematoma.

PMID- 9930489
TI  - Neovascularization after transmyocardial laser revascularization in a model of
      chronic ischemia.
AB  - BACKGROUND: The mechanism of clinical improvement after transmyocardial laser
      revascularization (TMR) is unknown. One hypothesis holds that TMR causes
      increased myocardial perfusion through neovascularization. This study sought to
      determine whether angiogenesis occurs after TMR in a porcine model of chronic
      myocardial ischemia. METHODS: Six miniature pigs underwent subtotal left
      circumflex coronary artery occlusion to reduce resting blood flow to 10% of
      baseline. After 2 weeks in the low-flow state, dobutamine stress echocardiography
      and positron emission tomography were performed to document ischemic, viable
      myocardium. The animals then underwent TMR and were sacrificed 6 months later for
      histologic and immunohistochemical analysis. RESULTS: Histologic analysis of the
      lased left circumflex region demonstrated many hypocellular areas filled with
      connective tissue representing remnant TMR channels. Histochemical staining
      demonstrated a highly disorganized pattern of neovascularization consistent with
      angiogenesis located predominantly at the periphery of the channels.
      Immunohistochemical analysis confirmed the presence of endothelial cells within
      neovessels. Vascular density analysis revealed a mean of 29.2+/-3.6 neovessels
      per high-power field in lased ischemic myocardium versus 4.0+/-0.3 (p<0.001) in
      nonlased ischemic myocardium. CONCLUSIONS: This study provides evidence that
      neovascularization is present long term in regions of ischemic, viable myocardium
      after TMR. Angiogenesis may represent the mechanism of clinical improvement after
      TMR.

PMID- 9930490
TI  - Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in
      the aged heart.
AB  - BACKGROUND: Recently we have reported a novel myo-protective protocol "adenosine
      enhanced ischemic preconditioning" (APC), which extends and amends the protection
      afforded by ischemic preconditioning (IPC) by both reducing myocardial infarct
      size and enhancing postischemic functional recovery in the mature rabbit heart.
      However, the efficacy of APC in the senescent myocardium was unknown. METHODS:
      The efficacy of APC was investigated in senescent rabbit hearts and compared with
      magnesium-supplemented potassium cardioplegia (K/Mg) and IPC. Global ischemia
      (GI) hearts were subjected to 30 minutes of global ischemia and 120 minutes of
      reperfusion. Ischemic preconditioning hearts received 5 minutes of global
      ischemia and 5 minutes of reperfusion before global ischemia. Magnesium
      supplemented potassium cardioplegia hearts received cardioplegia just before
      global ischemia. Adenosine-enhanced ischemic preconditioning hearts received a
      bolus injection of adenosine in concert with IPC. To separate the effects of
      adenosine from that of APC, a control group (ADO) received a bolus injection of
      adenosine 10 minutes before global ischemia. RESULTS: Infarct size was
      significantly decreased to 18.9%+/-2.7% with IPC (p<0.05 versus GI); 17.0%+/-1.0%
      with ADO (p<0.05 versus GI); 7.7%+/-1.3% with K/Mg (p<0.05 versus GI, IPC, and
      ADO); and 2.1%+/-0.6% with APC (p<0.05 versus GI, IPC, ADO, and K/Mg; not
      significant versus control). Only APC and K/Mg significantly enhanced
      postischemic functional recovery (not significant versus control). CONCLUSIONS:
      Adenosine-enhanced ischemic preconditioning provides similar protection to K/Mg
      cardioplegia, significantly enhancing postischemic functional recovery and
      decreasing infarct size in the senescent myocardium.

PMID- 9930491
TI  - Influence of functional tricuspid regurgitation on right ventricular function.
AB  - BACKGROUND: Although right ventricular (RV) function has been extensively studied
      during the past decade, few reports have described the influence of functional
      tricuspid regurgitation (TR) on RV function. METHODS: One hundred forty-two
      patients with left-side valvular heart disease associated with TR were enrolled
      in the study and divided into three groups according to tricuspid annular
      diameter: group 1 (n = 66), tricuspid annular diameter less than 40 mm; group 2
      (n = 58), tricuspid annular diameter of 40 to 50 mm; and group 3 (n = 18),
      tricuspid annular diameter greater than or equal to 50 mm. In groups 2 and 3, the
      right heart parameters had deteriorated to the point that TR repair was
      necessary. The mean follow-up period was 102 months after the operation. RESULTS:
      In each of the three groups, as pulmonary arteriolar resistance index increased,
      RV forward stroke work index increased in a linear fashion. The slope of the
      linear regression line was progressively less in group 1, 2, and 3
      preoperatively. Postoperatively, this line moved in a parallel manner in group 1
      and became steeper in group 2, consequently becoming similar in both groups.
      However, in group 3, although the slope became steeper in spite of a remarkable
      decrease of TR, it remained less when compared with groups 1 and 2. In addition,
      the right heart parameters also improved, but still remained worse in group 3
      than group 2; 7 patients undergoing a flexible annuloplasty have shown gradual
      aggravations in TR and late postoperative clinical manifestations. CONCLUSIONS:
      Functional TR with severely dilated annulus may produce an irreversible
      deterioration of RV function. The preoperative relationship between pulmonary
      arteriolar resistance index and RV forward stroke work index, that is, RV
      systolic function to pressure afterload, might predict a postoperative fate of
      the right heart function.

PMID- 9930492
TI  - Does bilateral internal thoracic artery grafting increase surgical risk in
      diabetic patients?
AB  - BACKGROUND: The purpose of this study was to determine whether, with appropriate
      techniques, diabetic patients could benefit from the advantages of double
      internal thoracic artery (ITA) coronary bypass without an increased hospital
      risk. METHODS: Between January 1990 and December 1996, 207 consecutive diabetic
      patients underwent coronary artery bypass graft operations. In 74 patients both
      arteries (bilateral ITA group) were used, whereas 133 patients received one ITA
      and vein grafts or vein grafts alone (nonbilateral group). Patients in the
      bilateral ITA group were younger (p<0.0001), predominantly male (p<0.0001), and
      were operated on more electively. The internal thoracic arteries were harvested
      by skeletonization without electrocautery, and strict glycemic control was
      pursued. RESULTS: No death was observed in the bilateral ITA group, whereas 7
      patients died in the nonbilateral ITA group (p<0.05). Deep sternal wound
      infection was observed in 2 patients in the nonbilateral ITA group (1.5%) and in
      none of the bilateral ITA group (p = NS). There was no significant difference in
      the morbidity rate between the two groups except for greater blood losses in the
      bilateral ITA group. CONCLUSION: Double ITA coronary revascularization in young
      diabetic patients was performed without increased morbidity and mortality. The
      low rate of sternal wound infections may be related to ITA harvesting by a
      skeletonization technique, but larger studies are required to confirm these data.

PMID- 9930493
TI  - Steal phenomenon from mammary side branches: when does it occur?
AB  - BACKGROUND: The hemodynamic significance of patent mammary graft side branches is
      still controversial. This study was designed to evaluate the potential for flow
      steal of patent mammary side branches in different hemodynamic conditions.
      METHODS: Echo-Doppler measurement of mammary graft flow was performed at rest and
      after dipyridamole-induced coronary vasodilatation in 10 patients with
      angiographic demonstration of evident mammary graft side branches (study group)
      and in 10 matched control patients (control group). Concomitant thallium-201
      myocardial scintigraphy was performed to assess the adequacy of mammary flow to
      the myocardial oxygen demand. Patients of the study group were also submitted to
      flow evaluation in condition of selective muscular or combined systemic and
      coronary relaxation. RESULTS: No difference in mammary flow and adequacy to
      myocardial oxygen demand was detected between patients of the study and control
      groups both at rest and after dipyridamole infusion. In patients with patent side
      branches the systolic-to-diastolic flow ratio was maintained in case of combined
      coronary and peripheral vasodilatation, whereas selective muscular relaxation led
      to an increase in the systolic and a reduction in the diastolic flow.
      CONCLUSIONS: Flow steal from patent mammary graft side branches is possible only
      in case of selective muscular vasodilatation. As this situation is unlikely to
      occur in the clinical setting, the potential for flow steal of mammary side
      branches in cardiac surgery patients seems to be minimal.

PMID- 9930494
TI  - Fucoidin reduces coronary microvascular leukocyte accumulation early in
      reperfusion.
AB  - BACKGROUND: Leukocytes rapidly accumulate in the heart early in reperfusion after
      ischemia, contributing to reperfusion injury. The purpose of this study was to
      determine whether treatment with the selectin blocker fucoidin (FCN) would
      attenuate early leukocyte retention in coronary venules and capillaries during
      low flow reperfusion. METHODS: Isolated rat hearts subjected to 30 minutes of 37
      degrees C, no-flow ischemia were initially reperfused with blood containing
      labeled leukocytes, followed by reperfusion with a Krebs red cell solution. The
      deposition of leukocytes in coronary capillaries and venules was observed using
      intravital microscopy. Three groups were studied: nonischemic control hearts,
      untreated postischemic hearts reperfused at low flow, and postischemic hearts
      reperfused at low flow, where both the hearts and the blood reperfusate were
      pretreated with FCN (0.36 mg/mL blood). RESULTS: In the ischemia-reperfusion
      group, we observed a rapid and significant increase in leukocyte accumulation in
      both capillaries and venules. Treatment with FCN significantly reduced the
      leukocyte accumulation in both capillaries and venules (p<0.05). In addition, FCN
      significantly reduced the persistence of leukostasis in both capillaries and
      venules, indicating that FCN affected a transient adhesion process. CONCLUSIONS:
      These results suggest that the selectin family of leukocyte-endothelial cell
      adhesion proteins mediates the initial retention of leukocytes in both coronary
      capillaries and venules during reperfusion. Selectin blockade may be effective in
      reducing the contribution of leukocytes to early reperfusion injury.

PMID- 9930495
TI  - Comparison of troponin-I and troponin-T after pediatric cardiovascular operation.
AB  - BACKGROUND: Although the diagnostic value of troponin-T in childhood is
      documented, little is known about the significance of troponin-I. It was the aim
      of this study to compare the diagnostic value of troponin-I and troponin-T in
      children and newborns to assess the perioperative potential myocardial damage.
      METHODS: Forty-eight children, mean, 51+/-54 months (mean value +/-1 standard
      deviation) (range, 1 day to 204 months) undergoing cardiac operation were
      prospectively enrolled in the present study. Troponin-I, troponin-T, creatine
      kinase (CK), and the MB isoenzyme were measured before operation and
      postoperatively within 2 days. RESULTS: Postoperative values of troponin-I for
      children undergoing extracardiac operation were in the normal range. In children
      with interventions through the right atrium (n = 10) the mean value increase to
      6.5+/-6.1 microg/L (range, 1.8 to 24.3 microg/L) and even to a mean of 29.9+/
      21.1 microg/L (range, 7.5 to 90 microg/L) (p<0.01) in children with atrial and
      additional ventricular surgical approach (n = 23). Troponin-I was of equal
      specificity and sensitivity compared to troponin-T, excepted in patients with
      postoperative renal failure in whom troponin-T raised to false pathological
      results. CONCLUSIONS: For detection of perioperative myocardial damage troponin-I
      shows a higher specificity than CK-MB activity and CK-MB mass. The diagnostic
      value of troponin-I is similar to troponin-T, but compared with troponin-T, it
      has the advantage of not being influenced by renal failure.

PMID- 9930496
TI  - Atrioventricular septal defect with tetralogy of Fallot: results of surgical
      correction.
AB  - BACKGROUND: The outcome of surgical correction of complete atrioventricular
      septal defect with tetralogy of Fallot has improved in recent years. Controversy
      exists about the optimal approach to this complex lesion. Our experience over the
      past 8 years with a single technique is reviewed. The important anatomic features
      of this lesion are discussed in relation to our method of repair. METHODS:
      Between 1988 and 1996, 11 consecutive patients underwent correction of complete
      atrioventricular septal defect with tetralogy of Fallot. Nine patients had
      undergone prior palliative shunts. The two-patch technique for atrioventricular
      septal defect was used. The ventricular septal defect was closed through a right
      ventriculotomy in each case. The commissure between the superior and inferior
      bridging leaflets of the left portion of the common atrioventricular valve was
      closed in each patient. Management of the right ventricular outflow tract was
      individualized. RESULTS: There was one mortality in the early postoperative
      period. One patient required reoperation for closure of a dehiscent left
      atrioventricular valve cleft. All survivors are currently in New York Heart
      Association functional class I or II at follow-up ranging from 2 to 101 months.
      CONCLUSIONS: Atrioventricular septal defect with tetralogy of Fallot can be
      corrected with low mortality using the two-patch technique and closure of the
      ventricular septal defect through a combined approach using a right
      ventriculotomy and right atriotomy. Routine closure of the commissure of the left
      portion of the atrioventricular valve results in a low incidence of
      regurgitation. A good functional result can be achieved in most patients at
      intermediate-term follow-up.

PMID- 9930497
TI  - Percutaneous coronary sinus cannulation guided by transesophageal
      echocardiography.
AB  - We investigated whether percutaneous cannulation of the coronary sinus could be
      accomplished without fluoroscopy using transesophageal echocardiography in
      patients undergoing minimally invasive cardiac operations. The coronary sinus was
      cannulated without significant complications using transesophageal
      echocardiography in 10 of 11 patients (mean, 10.5 minutes). Percutaneous
      cannulation of the coronary sinus can be accomplished in a safe and efficient
      manner using transesophageal echocardiography without the need for fluoroscopy.

PMID- 9930498
TI  - Transposition of the great arteries and isolated origin of the sinus node artery.
AB  - We report the cases of 2 newborns who underwent at 7 days of age an arterial
      switch operation for transposition of the great arteries with a rare coronary
      anomaly: the left and right coronary arteries originated with a single ostium
      from sinus 1 and the sinus node artery had an isolated origin from sinus 2. The
      sinus node artery was reimplanted into the new aorta in both patients. Both
      babies were discharged in sinus rhythm. Preserving the vascularization of the
      sinus node may avoid the occurrence of postoperative atrial rhythm disturbances.

PMID- 9930499
TI  - Leiomyosarcoma of the pulmonary artery.
AB  - Primary leiomyosarcoma of the pulmonary artery is an extremely rare tumor that is
      frequently misdiagnosed as chronic pulmonary embolism. In the present case, early
      diagnosis and location in the left pulmonary artery permitted resection by
      pneumonectomy with total cardiopulmonary bypass.

PMID- 9930500
TI  - Damage to the circumflex coronary artery during mitral valve repair with sliding
      leaflet technique.
AB  - We report a case of damage to the circumflex coronary artery during mitral valve
      repair using sliding leaflet technique in a patient with a posterior mitral
      leaflet prolapse and coronary artery disease who underwent mitral valve
      reconstruction using Carpentier's technique and coronary artery bypass grafting.
      This case underscores the risk of circumflex coronary artery injury during mitral
      valve reconstruction, especially in patients with left coronary dominance or
      codominance, and therefore emphasizes the importance of knowing the coronary
      artery anatomy preoperatively. The use of intraoperative transesophageal
      echocardiography is mandatory for the evaluation of mitral valvuloplasty.

PMID- 9930501
TI  - Compression of anomalous circumflex coronary artery by a prosthetic valve ring.
AB  - Anomalous origin of the circumflex coronary artery from the right aortic sinus,
      with a retroaortic course, is usually without consequence. We report a patient
      who underwent aortic valve replacement for bicuspid aortic valve. The prosthesis
      sewing ring distorted the circumflex, producing myocardial infarcts and sudden
      death during exercise.

PMID- 9930502
TI  - Pelvic leiomyoma in the right atrium.
AB  - Intravenous leiomyomatosis is a condition characterized by intravenous growth of
      histologically benign smooth muscle tumor, originating in the uterus. A case of
      intravenous leiomyomatosis with right atrial extension in a 64-year-old woman is
      described. The atrial tumor was successfully removed with a single-stage approach
      via sternolaparotomy and total circulatory arrest using cardiopulmonary bypass.

PMID- 9930503
TI  - Off-pump coronary bypass using interposed radial artery graft.
AB  - We describe a patient with severely diseased ascending aorta and small internal
      mammary arteries, who underwent off-pump coronary artery bypass to the left
      anterior descending coronary artery and right coronary artery using composite
      arterial grafts consisting of the pedicled proximal internal mammary artery and
      interposed radial artery graft. The interposed radial artery graft provides
      advantages, such as making coronary anastomosis on the beating heart easier and
      to increasing the flow potentiality of the internal mammary artery.

PMID- 9930504
TI  - Primary desmoid tumor of the posterior mediastinum.
AB  - We describe a unique case of a de novo desmoid tumor of the posterior mediastinum
      in a 21-year-old nulligravida. The tumor recurred twice despite its
      histologically confirmed radical extirpations. Because of the aggressive local
      behavior of desmoid tumors and their unusual locations, which prevent wide
      excision margins, we favor the early consideration of adjuvant therapy.

PMID- 9930505
TI  - Daily and long-term balloon dilation via minitracheostomy in cicatric bronchial
      stenosis.
AB  - We developed balloon dilation for bronchial stenosis via minitracheostomy. The
      balloon catheter was introduced via minitracheostomy into the stenotic bronchus.
      The balloon was inflated 4 hours per day. We conducted this procedure for a
      tuberculous cicatric stenosis of the left lower lobe bronchus. The bronchus was
      sufficiently dilated after eight applications. Compared with conventional balloon
      dilation via the mouth, the patient had less discomfort and could undergo
      treatment for a longer time and more frequently.

PMID- 9930506
TI  - Left ventricular pseudoaneurysm after epicardial patch electrode placement.
AB  - There are many known complications of implantable cardioverter-defibrillator
      placement. We treated a patient in whom a left ventricular pseudoaneurysm
      developed secondary to epicardial patch electrode placement and cardioverter
      defibrillator implantation. The presenting symptoms, diagnostic evaluation, and
      surgical repair are described.

PMID- 9930507
TI  - A new minimally invasive approach to the subclavian artery.
AB  - Aneurysms of the subclavian artery are rare. We report a case in which an
      aneurysm of the right subclavian artery presented as localized atrophy of the
      deltoid muscle. Operative repair was accomplished by a new minimally invasive
      surgical approach.

PMID- 9930508
TI  - Recurrence of stage I thymoma 32 years after total excision.
AB  - Malignant thymomas are invasive and recur frequently, but noninvasive thymomas
      rarely do so. We report on a case of recurrent thymoma in a 50-year-old white
      man, 32 years after total excision of a stage I thymoma. We stress the importance
      of long-term follow-up in all patients.

PMID- 9930509
TI  - A brimmed valved conduit in repair of fibrous skeleton abscess.
AB  - Aortomitral common annular involvement, which is not uncommon in infective
      endocarditis, necessitates deliberate surgical procedures. To repair fibrous
      skeleton abscess accompanied with annuloaortic ectasia, we used a brimmed valved
      conduit. Tension-free reconstruction of the aortic root and aortomitral common
      annulus was easily performed with this method.

PMID- 9930510
TI  - Hydatid cyst of the interventricular septum in a 3.5-year-old child.
AB  - An asymptomatic cardiac cyst located in the interventricular septum was diagnosed
      in a 3.5-year-old child by echocardiographic findings. Surgical ablation was done
      and histopathologic analysis confirmed a hydatid cyst. The patient was discharged
      without symptoms.

PMID- 9930511
TI  - The surgical importance of coronary sinus orifice atresia.
AB  - Coronary sinus orifice atresia is rare. We describe two cases, one with an
      atrioventricular septal defect and another with supracardiac totally anomalous
      pulmonary venous drainage. The association with the latter has not been described
      previously. The importance of diagnosing the defect is emphasized and surgical
      treatment is discussed.

PMID- 9930512
TI  - Repair of right ventricular rupture complicating mediastinitis.
AB  - A treatment strategy for rupture of right ventricle complicating mediastinitis is
      presented. We used two strips of anterior rectus sheath to buttress the
      ventricular closure during femoral-femoral bypass.

PMID- 9930513
TI  - Facile left ventricular deairing by administration of cardioplegia into the left
      ventricular vent.
AB  - De-airing of left heart structures during minimally invasive valve operations is
      often difficult. A method of using a left ventricular vent temporarily hooked to
      the cardioplegia cannula for facile left ventricular deairing is described.
      Routine use of this simple method coupled with transesophageal echocardiography
      monitoring simplifies the process of left ventricular deairing in minimally
      invasive or standard valvular operations.

PMID- 9930514
TI  - Biventricular cannulation for the Thoratec ventricular assist device.
AB  - The Thoratec biventricular assist device has been used extensively as a bridge to
      heart transplantation. Right atrial cannulation has always been used during right
      ventricular support, however diminished filling and output of the right
      ventricular assist device have been noticed when compared with filling and output
      of the left ventricular assist device. We describe a technique to directly
      cannulate the right ventricle to maximize filling and output of the right
      ventricular assist device.

PMID- 9930515
TI  - Three-graft technique for ascending aorta and total aortic arch replacement.
AB  - We have developed a procedure for total aortic arch replacement using three
      separate Hemashield grafts and establishing deep hypothermic circulatory arrest
      and continuous retrograde cerebral perfusion followed by antegrade cerebral
      perfusion. This method is technically simple and yields secure anastomoses.

PMID- 9930516
TI  - Endoscopic harvesting of the radial artery as a coronary artery bypass graft.
AB  - With an endoscopic approach we harvested the radial artery as a coronary artery
      bypass graft, using two transverse 2-cm incisions in the forearm. There were no
      complications in the forearm and hand. The short-term results of the radial
      artery graft were good.

PMID- 9930517
TI  - Reduction of wound healing problems after median sternotomy by use of retention
      sutures.
AB  - Obese people have a higher risk of sternal wound dehiscence resulting from
      traction of suprasternal tissue. In such patients we recommend the use of
      retention sutures with extracorporeal plates to improve tissue connection and to
      disburden fascia and skin sutures. This augmented closure is simple and effective
      and, since 1996, has prevented wound healing problems in more than 50 patients
      with a body mass index greater than 27.

PMID- 9930518
TI  - Mitral valve replacement with homograft.
AB  - The technique for replacement of the mitral valve with a mitral valve homograft
      is described. Principles include side-by-side approximation of the papillary
      muscles using multiple stitches of fine monofilament suture, direct attachment of
      the annulus of the mitral homograft to the annulus of the patient, and support of
      the repair by remodeling annuloplasty ring.

PMID- 9930519
TI  - Lyman A. Brewer III (1907-1988): surgeon-scientist, inspirational teacher, and
      humanist.
AB  - Dr. Lyman Augustus Brewer III, a distinguished, colorful thoracic surgeon and
      among the first to practice that specialty in the West, died on June 25, 1988, in
      Los Angeles, California, after a courageous battle with lymphoma. Dr. Brewer was
      a great humanist, innovative clinical surgeon, charismatic teacher, and surgical
      leader. In World War II, Lieutenant Colonel Brewer served in the Second Auxiliary
      Surgical Group in the Mediterranean and European theaters and helped define
      criteria that became the standard for the management of thoracic war injuries.
      Out of this experience he authored the classic paper, "The Wet Lung in War
      Casualties." Dr. Brewer's scientific contributions embraced the broad spectrum of
      thoracic surgical topics, including treatment of tuberculosis, classification of
      lung cancer, bronchial stump buttressing using the pericardial fat pad (Brewer
      fat pad), and management of esophageal perforation. Dr Brewer wrote seven books
      and more than 100 papers, and served as First Vice President of The American
      College of Surgeons and as President of the American Association for Thoracic
      Surgery, The Society of Thoracic Surgeons, and The Pacific Coast Surgical
      Association.

PMID- 9930520
TI  - Effects of cardiopulmonary bypass on leukocyte and endothelial adhesion
      molecules.
AB  - During the inflammatory response, triggered by cardiopulmonary bypass,
      interaction between activated leukocytes, platelets, and endothelial cells is
      mediated through the expression of three main groups of adhesion molecules: the
      selectins, the integrins, and the immunoglobulin superfamily. The selectins,
      which mediate the initial rolling of the leukocyte on the endothelium, are
      divided in three subgroups: L-selectin is expressed on all three leukocyte types,
      P-selectin is expressed on platelets and endothelial cells, and E-selectin is
      only expressed on endothelial cells. Integrins can be found on most cell types,
      consist of an alpha and a beta subunit and mediate firm adhesion of the leukocyte
      and migration into the tissues. They are classified into subgroups according to
      the type of their beta subunit. Immunoglobulins such as ICAM-1 and VCAM-1 are
      expressed mainly on endothelium and act as ligands for certain integrins. This
      review article summarizes the existing, and rapidly expanding, literature
      concerning the effects of cardiopulmonary bypass on the expression of leukocyte
      and endothelial adhesion molecules. Deeper understanding of the, behavior and the
      role of adhesion molecules during cardiopulmonary bypass may facilitate effective
      intervention in the inflammatory response process and suppression of its adverse
      effects.

PMID- 9930521
TI  - The platelet in cardiopulmonary bypass.
AB  - Platelets are the smallest of the blood cells and are known to be activated
      during cardiopulmonary bypass. They play a role in many associated complications.
      Both quantitative and qualitative platelet defects have been demonstrated,
      resulting in microvascular hemorrhage and thromboembolism. As their interactions
      with endothelium and other blood cells are unraveled, the important contribution
      they make toward the systemic inflammatory response to operation seen in
      cardiopulmonary bypass is increasingly evident. In this review, we consider
      platelet activation during cardiopulmonary bypass, the resultant clinical
      effects, and potential approaches to therapy and prevention.

PMID- 9930522
TI  - As originally published in 1992: The Carpentier-Edwards pericardial aortic valve:
      intermediate results. Updated in 1998.

PMID- 9930523
TI  - Controlled perfusion protects lung grafts during a transient early increase in
      permeability.

PMID- 9930524
TI  - "Radial" and "modified Papworth" maze procedures for atrial fibrillation.

PMID- 9930525
TI  - Left atrial wall plication for valve replacement in extensively calcified
      posterior mitral annulus.

PMID- 9930526
TI  - Reconstruction plates for internal fixation of flail chest.

PMID- 9930527
TI  - Aortic valve replacement using circulatory arrest.

PMID- 9930528
TI  - Modified incision for the long saphenous vein harvest.

PMID- 9930529
TI  - Superior sulcus tumors.

PMID- 9930531
TI  - Angiogenesis in lung cancer.

PMID- 9930530
TI  - Growth of the subclavian artery to pulmonary artery anastomosis: a caveat.

PMID- 9930532
TI  - Angiotensin-converting enzyme inhibitors during acute revascularization.

PMID- 9930533
TI  - Ischemic preconditioning in children undergoing open heart operation.

PMID- 9930534
TI  - Experimental approaches to vocal fold alteration: introduction to the
      minithyrotomy.
AB  - Treatment of challenging laryngeal disorders, such as lamina propria loss or
      neuromuscular dysfunction, may require novel approaches and techniques. This
      paper discusses an evolution of experimental techniques for treatment of lamina
      propria loss and use of the minithyrotomy. These techniques have been used for
      surgical access for lamina propria substitution, as well as placement of
      stimulating electrodes. The minithyrotomy is tolerated well by patients, provides
      access for microscopic instruments with the surgeon's hand close to the tissue of
      interest, avoids intralaryngeal mucosal incisions, and lines up the direction of
      dissection in an anterior-to-posterior orientation. This orientation is favorable
      for particular situations herein discussed. We present anatomic and physiologic
      concepts relevant to the surgical treatment of lamina propria dysfunction, as
      well as presenting our clinical experience. This paper is not intended to state
      how these difficult problems should be handled, but rather, to present our
      experience in techniques that may prove useful through further development.

PMID- 9930535
TI  - Ectasias and varices of the vocal fold: clearing the striking zone.
AB  - Vascular malformations such as ectasias and varices (Es and Vs) are frequently
      encountered in patients who present with recurrent vocal fold hemorrhage and/or
      other traumatic vocal fold lesions. This study examined Es and Vs with regard to
      their anatomic presentation, phonomicrosurgical management, and treatment
      outcome. Forty-two patients (39 of them singers) were treated for a total of 87
      Es and Vs: 67 of 87 (77%) were on the superior surface of the vocal fold and 20
      of 87 (23%) were on the medial surface of the vocal fold. Eighty-three percent
      were located in the middle musculomembranous region (the striking zone), where
      the greatest aerodynamically induced shearing stresses occur during phonation.
      Treatment was performed with carbon dioxide laser cauterization (13 patients), or
      a new technique utilizing cold instrument excision by means of epithelial
      cordotomies (23 patients), while a combined approach was employed in 6 patients.
      Comparisons of preoperative and postoperative stroboscopy revealed improvement or
      no significant change in all patients in whom the cold instrument technique was
      used, and increased epithelial stiffness was noted in 4 of 19 patients in whom
      the carbon dioxide laser was used. Clearing the striking zone appears to have
      halted further hemorrhages by removing the the fragile Es and Vs from this injury
      prone region of the vocal fold. Interpretations of stroboscopic examinations were
      directed at providing new insights into the biomechanical forces of vocal fold
      vibration that probably contribute to the genesis of Es and Vs in the vocal
      folds.

PMID- 9930536
TI  - Ablation of Teflon granulomas in the canine larynx with the free-electron laser.
AB  - This study develops a canine model for the treatment of laryngeal Teflon
      granulomas and demonstrates endoscopic ablation using the free-electron laser
      (FEL) set at a wavelength of 8.5 microm. Laryngeal Teflon granulomas may cause
      dysphonia and airway obstruction, and they are difficult to remove. The infrared
      absorption spectrum of Teflon reveals a strong absorption peak centered at 8.5
      microm. In this study, 12 dogs had the right vocal cord injected with Teflon
      paste. Two months later, Teflon granuloma formation was confirmed histologically.
      Laser incisions into the granulomas were performed at 3 different wavelengths:
      7.4 microm (FEL), 8.5 microm (FEL), and 10.6 microm (carbon dioxide laser).
      Histopathologic analysis was performed at 1 week and 6 weeks after the laser
      incisions. The FEL at the 8.5-microm wavelength was found to optimally ablate the
      Teflon granulomas, but the granulomas persisted in the specimens treated with 7.4
      microm (FEL) and 10.6 microm (carbon dioxide laser).

PMID- 9930537
TI  - Transverse infrahyoid approach to bilateral glottic tumors.
AB  - Glottic exposure and entry for vertical partial laryngectomy procedures has
      traditionally been through the subglottis. Although this approach is generally
      satisfactory for the resection of unilateral vocal cord lesions, it may be unsafe
      in cases in which tumors extend across the midline and/or subglottically. In
      these instances, we prefer the superior transverse infrahyoid approach to the
      glottis, which transects the petiole of the epiglottis and reflects the contents
      of the preepiglottic space posterior and superior. This improved visualization of
      the larynx has permitted precise tumor excision without sacrifice of uninvolved
      segments of the vocal cords. This procedure has been performed 35 times over a 15
      year period at our institution for the resection of bilateral glottic tumors,
      with and without subglottic extension. In none of the cases in which it has been
      employed was there a positive surgical margin.

PMID- 9930538
TI  - Immunologic and histologic observations in reovirus-induced otitis media in the
      mouse.
AB  - The goals of this study were to develop a mouse model for virally induced otitis
      media, and to study the immune response to infection. Intranasal inoculation of
      mice by reovirus was used to induce otitis media. Immunohistochemical evidence
      for the presence of reovirus in the nasopharynx, eustachian tubes, and middle
      ears and the amount of infiltrating B-cells and T-cells in those sites were
      serially evaluated by painlessly sacrificing animals over a 21 -day period.
      Reovirus antigen was detected in the middle ear mucosa by day 4 in 75% of
      infected animals, and histologic evidence for otitis media was found in 54% of
      all infected animals. A significant increase in B-cells in the nasopharynx and
      eustachian tubes was noted 7 to 10 days following infection. The number of
      infiltrating T-cells did not vary significantly from that in the control animals
      at any of the sites. These results provide a basis for further investigations of
      the immune response in otitis media.

PMID- 9930539
TI  - Endoscopic middle ear surgery.
AB  - One hundred sixty-five middle ear procedures were performed with an endoscope, a
      camera, and a video monitor instead of the microscope. The endoscope offers the
      following advantages: 1) it visualizes the whole tympanic membrane and the ear
      canal without having to manipulate the patient's head or the microscope, 2) it
      extends the operative field in transcanal procedures into structures usually
      hidden from the microscope (anterior tympanic perforation, posterior retraction
      pocket, facial recess, and hypotympanum), and 3) it visualizes structures from
      multiple angles as opposed to the microscope's single axis along the ear canal.
      Disadvantages of the endoscope include the one-handed surgical technique, a loss
      of depth perception, limited magnification, and the need for training. The
      endoscope holds the greatest promise in tympanoplasty and cholesteatoma surgery
      and should increase the utilization of transcanal over postauricular procedures.

PMID- 9930540
TI  - Application of labeling techniques to archival temporal bone sections.
AB  - Pathology of the human inner ear has traditionally been studied in celloidin
      embedded, hematoxylin and eosin-stained sections of the temporal bone. Although
      the traditional histologic approach has yielded valuable information, it is now
      possible to extend these studies to include analysis of molecules using
      immunohistochemical and histochemical staining techniques. Fourteen antibodies
      and 6 lectins have been applied to 420 archival, celloidin-embedded human
      temporal bone sections. Tissues had been fixed in 10% formalin, embedded in
      celloidin, sectioned, and stored for as many as 40 years. The staining
      intensities varied among sections, so they were ranked from 'no label" to "dense
      label." To investigate the relationships between the extent of postmortem changes
      (PMCs), storage time, and staining intensity for each antibody, the sections were
      graded according to their PMCs, which ranged from good preservation of the
      temporal bone histologic structure to severe postmortem autolysis. Although
      statistical analysis indicated that both extent of PMCs and storage time in
      general decrease the staining intensity, both poorly fixed tissue and sections
      stored for a long time can yield good immunostaining results with some
      antibodies.

PMID- 9930541
TI  - Optical tracking of a microscope for image-guided intranasal sinus surgery.
AB  - The objective of this study was to examine the effects of optical and tracking
      properties on the accuracy of an optically locatable operating microscope. The
      intraoperative arrangement was based on experimental results obtained from a
      skull model. Measurements were taken from 24 patients undergoing intranasal
      microscopic sinus surgery for various disorders. Two major groups of influencing
      factors were determined from measurements on the model: 1) optical properties of
      the microscope, such as the method of focal point adjustment, focal length, and
      magnification of the lens; and 2) tracking properties of the microscope, such as
      the distance of the digitizer to the tracked object, the number of reference
      infrared light-emitting diodes (IR-LEDs), and the area circumscribed by these IR
      LEDs. Patient measurements showed an overall spatial error of 2.39+/-1.15 mm with
      a laser-supported adjustment of the focal point of the microscope. Although the
      associated 95th percentile was at 4.36 mm, such a value is encouraging for
      further development of microscopically navigable systems. It must be noted that
      the noninvasive patient-to-image registration was performed on the basis of a
      computed tomographic image with a slice distance of 2 mm.

PMID- 9930542
TI  - Manometric study of paranasal sinus mucoceles.
AB  - A paranasal sinus mucocele is a chronic cystlike lesion characterized by slowly
      progressive remodeling and expansion of the surrounding osseous walls. If left
      untreated, it may cause significant facial deformity, ophthalmic disturbances,
      and, in the worst instance, intracranial complications. According to a review of
      the literature, there is a long-held view that positive pressure exists within
      paranasal sinus mucoceles; however, to our knowledge, pressure measurements have
      not been recorded in humans. In this study, pressure measurements were taken of 4
      paranasal sinus mucoceles by means of an 18-gauge needle probe and an amplified
      pressure transducer. The average value was +15 cm H2O with a range of +4 to +39
      cm H2O. This study confirms the long-standing assumption that positive pressure
      exists within paranasal sinus mucoceles. The magnitude of the pressure was
      comparable to that which was found to be associated with bone resorption in
      several previously published studies. Further studies are needed to determine
      whether positive pressure and osseous remodeling are causally related in this
      condition.

PMID- 9930543
TI  - Radiographic evaluation of children with nasopharyngeal obstruction due to the
      adenoid.
AB  - The adenoidal-nasopharyngeal ratio (ANR) was proposed as a convenient and
      practical method to evaluate adenoidal enlargement. We analyzed cephalometric
      radiographs of 150 children divided into 6 subgroups according to clinical
      assessment (possible adenoidectomy candidates [PACs] and controls) and age. Our
      purpose was to investigate the predictive reliability of different ANRs
      calculated on the same reference line. Each of the ANRs described in this study
      presented statistically significant differences between PACs and control groups,
      and highly significant correlations with clinical symptoms of nasal obstruction.
      Further, the mean adenoidal depth was significantly larger in PACs than in
      normals, and it was found that the adenoidal depth in PACs did not show a
      significant decrement with age. in contrast to normals. On the other hand,
      although nasopharyngeal depth was not different between PACs and normals, an age
      dependent increment was observed in PACs, in contrast to normals. Thus, it could
      be said that the ANR is a more reliable method for determining whether adenoidal
      hyperplasia is clinically significant or not, rather than the size of the adenoid
      or nasopharynx.

PMID- 9930544
TI  - Changes in head and neck tumor hypoxic fraction during split-course
      radiochemotherapy.
AB  - This study explored patterns of oxygen distribution in human tumors during
      primary radiochemotherapy. Patients with positive nodes from head and neck
      squamous cell carcinoma (n = 15) were investigated before therapy, before and
      after a 2-week respite, and at the end of the treatment. Intratumoral tissue
      oxygen tension (pO2) was measured with sterile polarographic needle electrodes
      and a computerized histography system. The 2 lowest pO2 classes, ie, 0 and 5 mm
      Hg, were designated the hypoxic fraction, and the mean and median pO2 were
      evaluated for each tumor. In the beginning, a marked variability in tissue pO2
      was found. The initial size of the hypoxic fraction ranged from 0% to 61% of
      measured values. At the end of treatment, 4 tumors showed an increase in mean
      pO2, and 7 tumors a lower mean pO2 in comparison to the initial values. However,
      an impressive finding was that the hypoxic fraction of 9 tumors became smaller
      during the pause, 1 tumor showed no change, and 1 showed an increase in hypoxic
      fraction. The results show that there is a widely distributed tissue oxygenation
      with marked hypoxic zones in human neck nodes. During radiochemotherapy, tissue
      oxygenation changed, with great intertumor variability. A tendency toward a
      decrease of the hypoxic fraction after the respite could be seen. This change in
      tumor oxygenation during therapy needs further evaluation.

PMID- 9930545
TI  - Titanium vocal fold medializing implant: introducing a novel implant system for
      external vocal fold medialization.
AB  - With the increasing worldwide spread of the Isshiki technique for external vocal
      fold medialization, some disadvantages and limitations have also emerged. and an
      increasing demand for a ready-made and standardized implant system can be
      observed. For this reason. I started experimental and clinical investigations
      with the goal of replacing the silicone with a safer material, and also
      simplifying and standardizing the surgical procedure. In particular, the danger
      of implant dislocation should be excluded with greater certainty. As a result, I
      have developed an implant made of medical-grade titanium. My surgical experiences
      in 20 patients with this newly developed titanium vocal fold medializing implant
      revealed that vocal fold medialization could be performed easily and that no
      perioperative complications occurred in any case. The major advantage was a
      significant reduction of operative time due to the preformed implant. This is not
      only more convenient for both the surgeon and the patient, but is also critical
      for obtaining optimal results due to the reduced intralaryngeal swelling and
      hematoma. The reduction of the glottic gap by the operation was statistically
      significant. Significant improvement of all voice parameters was achieved and
      demonstrated by a statistically significant reduction of the voice dysfunction
      index. Compared to the current techniques and implant systems, I see the
      following additional advantages: 1) titanium is a relatively safe implant
      material with excellent biocompatibility: 2) the design of the implant ensures
      optimal fixation and stabilization: 3) the implantation technique and handling is
      simple and time-saving; 4) the titanium sheet is easy to shape and adapt to the
      individual situation: and 5) only 2 sizes of implants, and no expensive
      instruments, are required.

PMID- 9930546
TI  - Carotid artery occlusion due to bacterial paranasal sinusitis.
AB  - Complications of paranasal sinusitis still continue to be a serious health
      problem. We present an orbita-related complication of sinusitis in a patient with
      diabetic ketoacidosis. It was not a rhinocerebral mucormycosis, but a bacterial
      sinusitis-induced development of left cavernous sinus thrombophlebitis and
      carotid artery occlusion. We discuss the diagnosis, surgical options, and
      clinical outcome.

PMID- 9930547
TI  - Brown tumor of the palate in a patient with primary hyperparathyroidism.

PMID- 9930548
TI  - AIDS-related plasmablastic lymphomas of the oral cavity and jaws: a diagnostic
      dilemma.
AB  - Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas are
      highly pleomorphic in their clinical, pathological, and biological features.
      Recent investigations have led to the identification of a particular type of AIDS
      related non-Hodgkin's lymphomas presenting in the oral cavity and jaws. This
      novel category of AIDS-related non-Hodgkin's lymphomas derives from B-cells and
      has been defined as plasmablastic lymphoma on the basis of its morphological and
      immunophenotypic features. Clinically, AIDS-related plasmablastic lymphoma is
      generally limited to the oral cavity at the time of diagnosis, although extension
      to distant sites frequently occurs at a later stage. Histologically, AIDS-related
      plasmablastic lymphoma is composed of a monomorphic and cohesive pattern of
      plasmablasts with basophilic cytoplasm. Phenotypically, AIDS-related
      plasmablastic lymphoma fails to express the most common B-cell-associated surface
      antigens, whereas it consistently expresses high levels of plasma cell-associated
      markers, including VS38c and CD138/syndecan-1. For the purpose of differential
      diagnosis, the morphological and immunophenotypic peculiarities of AIDS-related
      plasmablastic lymphoma clearly distinguish these lymphomas from other categories
      of AIDS-related non-Hodgkin's lymphomas, as well as from undifferentiated large
      cell carcinomas.

PMID- 9930549
TI  - Introduction: overview of chronic myeloproliferative disorders.

PMID- 9930550
TI  - Pathogenetic mechanisms in chronic myeloproliferative disorders: polycythemia
      vera, essential thrombocythemia, agnogenic myeloid metaplasia, and chronic
      myelogenous leukemia.
AB  - The stem cell origination of the clonal process in chronic myeloproliferative
      disorders (CMPDs) is well established. In chronic myelogenous leukemia (CML), the
      primary genetic process has been characterized. However, current information
      regarding the mechanisms of phenotypic diversity among the CMPD and the
      downstream effects of the chromosomal translocation in CML remains inconclusive.
      In this report, the current understanding regarding erythrocytosis in
      polycythemia vera (PV), thrombocytosis in essential thrombocythemia (ET), bone
      marrow fibrosis (BMF) in agnogenic myeloid metaplasia (AMM), and the connection
      between the genetic alteration and cellular transformation in CML will be
      discussed.

PMID- 9930551
TI  - Diagnostic criteria and prognosis in polycythemia vera and essential
      thrombocythemia.
AB  - Polycythemia vera (PV) and essential thrombocythemia (ET) are two
      myeloproliferative disorders (MPDs) that result from an acquired mutation of a
      single hematopoietic stem cell that gives the progeny of the stem cell a growth
      advantage over their normal counterparts. The incidence of both diseases appears
      to be similar. From time to time, PV has an atypical presentation making it
      difficult to differentiate from ET and other MPDs. Identification of a patient as
      having PV or ET generally follows the observation of elevated hematocrit or
      elevated platelet count. Thrombotic complications are the major cause of
      morbidity and mortality in both groups of patients. In PV, the frequencies of
      venous and arterial thrombosis are about equal, whereas venous thrombosis is less
      common in ET. Accurate diagnosis of these disorders is essential for proper
      treatment. The prognosis for untreated, asymptomatic ET patients is generally
      good, but quite poor for untreated PV patients. Proper treatments have been shown
      to reduce complications and significantly extend the life span for both groups of
      patients.

PMID- 9930552
TI  - Clinical parameters for determining when and when not to treat essential
      thrombocythemia.
AB  - Essential thrombocythemia (ET) is a myeloproliferative disorder that occurs
      primarily in middle-aged adults. ET is relatively benign compared with some of
      the other myeloproliferative disorders (MPDs), but there is still a high rate of
      morbidity and quality of life can be affected, especially by thrombotic and
      hemorrhagic complications. Two thirds of ET patients are symptomatic, but
      therapies are not benign. While alkylating agents, radioactive phosphorous, and
      hydroxyurea (HU) all have a leukemogenic risk, their use in high-risk and elderly
      patients may still be warranted in some circumstances. Use of nonmutagenic agents
      such as anagrelide, interferon-alpha (IFN), or low-dose aspirin has become an
      attractive alternative. However, the risks and benefits of treatment versus
      nontreatment should be based on clinical data and must be determined on an
      individual basis.

PMID- 9930553
TI  - Historical perspective on the treatment of essential thrombocythemia and
      polycythemia vera.
AB  - Since 1970, the treatment of essential thrombocythemia (ET) and polycythemia vera
      (PV) has evolved from alkylating agents to hydroxyurea (HU), and more recently to
      agents such as interferon-alpha (IFN) and anagrelide. While the earlier
      treatments for ET and PV have been successful in varying degrees, diagnosis of
      these disorders is being made earlier and in populations deemed at lower risk,
      but who may suffer greatly from the toxicity of long-term treatment with these
      agents. Thus, the risks and benefits of treatment versus nontreatment and between
      types of therapy have created a need for treatments that are safer for more
      people for greater lengths of time.

PMID- 9930554
TI  - Treatment of essential thrombocythemia with anagrelide.
AB  - Essential thrombocythemia (ET), the most common of the chronic myeloproliferative
      disorders, is characterized by thrombotic and hemorrhagic complications.
      Thrombotic complications predominate, endangering especially the older population
      and those with prior history of thrombotic episodes. However, because the life
      expectancy of ET patients is generally of normal length, caution must be
      exercised in treating these patients, and the complications of treatment must be
      weighed against the complications of the disease. Historically, most drugs used
      in the treatment of ET, such as alkylating agents and radiophosphorus, were
      carcinogenic themselves. Even hydroxyurea has recently come under investigation
      for its long-term mutagenicity. The newest drug, anagrelide, approved in March
      1997 specifically for ET, appears to be safe and well tolerated.

PMID- 9930555
TI  - Cost-effectiveness model of a phase II clinical trial of a new pharmaceutical for
      essential thrombocythemia: is it helpful to policy makers?
AB  - Essential thrombocythemia (ET) is a rare, chronic myeloproliferative disorder of
      unknown origin characterized by thrombocytosis, excessive megakaryocytes,
      hemorrhages, and thrombotic complications. Because of the high costs of care for
      persons with rare diseases, policymakers are concerned with both clinical
      effectiveness and cost-effectiveness of new treatments. Although the clinical
      efficacy of all new pharmaceutical agents for rare diseases is evaluated
      extensively in clinical trial settings before approval by the Food and Drug
      Administration (FDA), comparative phase III trials of a new agent with its major
      competitor are sometimes not possible to carry out, and estimates of cost
      effectiveness are therefore difficult to obtain. We describe methodologic issues
      associated with the development of economic models of new pharmaceutical agents
      for rare diseases and illustrate these issues with an analysis of a new therapy
      for ET. Anagrelide is a newly approved platelet aggregation inhibitor that can be
      used as primary therapy for ET. The agent reduces platelet counts by 50% in more
      than 70% of ET patients. Economic models suggest that, over the first year of
      anagrelide therapy, monthly costs for therapy and complications decreased from
      $775 to $490, the effectiveness improved to 98%, and the cost-effectiveness
      improved to $1,505 per major complication (gastrointestinal bleed, transient
      ischemic attack or stroke, or preinfarction angina or myocardial infarction)
      prevented. Sensitivity analyses indicate that, after the first 3 months of
      treatment, total costs of anagrelide treatment were in the range of $1,505 to
      $1,615 per major complication prevented. To make well-informed therapeutic
      decisions, policymakers and physicians require head-to-head studies of a new
      pharmaceutical agent with its major competitor. However, economic models can be
      used to derive estimates of cost-effectiveness of new pharmaceutical agents when
      such data are lacking. The interpretation of these models raises general issues
      related to the perspective of the investigator, study design, estimation of costs
      of care, rates of response, toxicity, survival, and the ability to generalize the
      results to other settings, as well as methodologic issues that are unique to rare
      diseases. If a comparative study found better therapeutic outcomes, then cost
      effectiveness models would be of limited usefulness. Almost all physicians would
      use the drug with the better therapeutic profile.

PMID- 9930556
TI  - Drug-induced immune thrombocytopenia: an overview of pathogenesis.
AB  - Many drugs are capable of causing antibody-mediated thrombocytopenia. Four, and
      perhaps five, different mechanisms have been implicated in the pathogenesis of
      this family of disorders. Some drugs become bound covalently to platelet membrane
      glycoproteins in vivo and stimulate the production of hapten-dependent antibodies
      that recognize drug-membrane protein targets. Others, such as quinidine, quinine,
      and sulfonamide antibiotics, induce the formation of an unusual class of
      antibodies that bind to membrane glycoproteins only when the drug (or one of its
      metabolites) is present in solution. Certain drugs trigger the production of true
      autoantibodies capable of binding to cell membrane glycoproteins in the absence
      of drug. Heparin-induced immune thrombocytopenia (HIT) is associated with
      antibodies specific for complexes formed between heparin and platelet factor 4
      (PF4), a basic protein of the chemokine family found normally in platelet alpha
      granules. Immune complexes consisting of heparin, PF4, and antibodies are
      important in the pathogenesis of HIT, but the exact mechanisms by which they
      cause platelet destruction and, in some patients, thrombosis are not yet fully
      understood. Finally, thrombocytopenia in patients treated with recently
      introduced inhibitors of the platelet fibrinogen receptor (ligand mimetics) is
      thought to result from antibodies specific for ligand-induced binding sites
      (LIBS) on this receptor, but this mechanism has not yet been established.

PMID- 9930557
TI  - Antigens involved in heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT), a common side effect of heparin therapy,
      can be life-threatening. Following treatment with heparin, platelet factor 4
      (PF4) is released into the circulation. Heparin can bind to PF4 to form a
      reactive antigen on the platelet. The formation of large heparin-PF4 (H-PF4)
      complexes that can react with HIT antibodies depends on the concentrations of
      heparin and PF4. Antibodies involved in HIT are usually of the IgG class, but can
      be IgA or IgM; Fab and Fc fragments are necessary for the activation of
      platelets. In a minority of cases of HIT, antibodies to H-PF4 are not present,
      but antibodies to other cytokines have been found. These antibodies frequently
      react either with interleukin-8 (IL-8) or with neutrophil-activating peptide 2
      (NAP-2). Discontinuation of heparin has been the traditional first step in the
      treatment of HIT. Drugs that inhibit thrombin directly may be necessary in some
      cases.

PMID- 9930558
TI  - A mouse model for heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) occurs in 1% to 3% of patients receiving
      heparin and results from the development of antibodies that recognize heparin
      platelet factor 4 (H-PF4) complexes that form on the surface of activated
      platelets and on the vascular endothelium. With the aim of studying the
      pathogenic importance of these anti-H-PF4 antibodies in vivo, we attempted to
      create an animal model of HIT. Such a model was produced by immunization of naive
      mice with affinity-purified IgG anti-H-PF4 antibodies from two patients with HIT.
      The immunized mice developed specific antibodies (anti-idiotypic) against the
      human anti-H-PF4 antibodies and 2 months later, anti-anti-idiotypic antibodies
      appeared, which functionally resembled the human HIT antibody. Indeed, when the
      animals bearing anti-anti-idiotypic antibodies were injected with heparin for 4
      days, a significant decrease in their platelet counts was observed; however,
      heparin treatment was not associated with thrombosis in any of the immunized
      mice. Similar to the observation in HIT patients, injections of equivalent doses
      of low-molecular-weight (LMW) heparin to the immunized animals did not induce
      thrombocytopenia. The results of this study support the importance of anti-H-PF4
      antibodies in the pathogenesis of HIT. The mouse HIT model may provide a
      convenient system for studies on the immunoregulation of anti-H-PF4 expression
      and for evaluation of potential therapeutic modalities.

PMID- 9930559
TI  - The clinical management of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an immunologic complication of drug
      therapy with potentially serious venous and arterial thrombotic sequelae. Recent
      studies have provided insight into the molecular and cellular basis of HIT
      underlying the diagnosis and treatment of this syndrome. Because various
      approaches to HIT treatment have resulted in mixed success, the use of heparin
      substitutes, other anticoagulant agents, and adjunctive therapy needs to be
      clarified. For patients with pre-existing conditions such as deep venous
      thrombosis or pulmonary embolism, new understanding of the clinicopathologic
      syndrome of HIT offers the promise of improved antithrombotic therapy. The
      participation of thrombin in HIT suggests that specific (hirudin and argatroban)
      thrombin inhibitors may be ideal agents for treating acute HIT.

PMID- 9930561
TI  - Plasmapheresis in the management of heparin-induced thrombocytopenia.
AB  - This study investigated the role of plasmapheresis in the treatment of severe
      heparin-induced thrombocytopenia (HIT). Patients diagnosed with HIT were divided
      into three experimental groups. Sixteen patients did not receive plasmapheresis
      (control). Twenty-one patients received plasmapheresis within 4 days of onset of
      thrombocytopenia (early group). Seven patients received plasmapheresis 4 days or
      later after onset (late group). Most patients underwent a second plasmapheresis
      24 to 48 hours after the first, when clinically indicated, and platelet
      aggregation tests became negative in 75% of these patients. Heparin
      administration was discontinued after 1.4 days in the early group of patients and
      4.2 days in the late group, as compared with 2.4 days in the control group. The
      30-day mortality rate was 4.8% among patients in the early group and 57% in the
      late group, as compared with 32% in the control group. Platelet recovery time,
      incidence of thrombotic events, and length of hospital stay were similar in the
      early group and controls, but were somewhat higher in the late group. Thus,
      plasmapheresis within 4 days of the onset of thrombocytopenia reduced mortality
      in HIT patients, whereas plasmapheresis after 4 days was not beneficial. There
      were no adverse events related to plasmapheresis. These findings suggest that
      plasmapheresis may be useful in the treatment of HIT when initiated within 4 days
      of onset of thrombocytopenia.

PMID- 9930560
TI  - Laboratory tests for heparin-induced thrombocytopenia: a multicenter study.
AB  - A multicenter clinical trial of the thrombin inhibitor argatroban (Novastan;
      Texas Biotechnology, Houston, TX; Smith-Kline Beecham Pharmaceuticals,
      Philadelphia, PA) was recently conducted in patients with heparin-induced
      thrombocytopenia (HIT) and HIT that had progressed to thrombosis (HITTS). In
      patients defined by the inclusion/exclusion criteria, the utility of three
      diagnostic HIT assays was investigated: the platelet aggregation assay, the
      serotonin release assay (SRA), and the enzyme-linked immunosorbent assay (ELISA)
      for the antibody to the heparin-platelet factor 4 (H-PF4) complex. Confirmation
      was made in 26%, 55%, and 64% of the patients, respectively (n = 199 patients;
      512 to 606 samples; P < .001 platelet aggregation assay v SRA v ELISA). Patients
      who progressed to HITTS (n = 98) were more often confirmed than were HIT patients
      without associated thrombosis (n = 101) (P < .05). Confirmation by platelet
      aggregation assay and SRA results generally was associated with a higher antibody
      titer. However, a minimum critical titer could not be identified, because all
      patterns of positive and negative results by the platelet aggregation assay, SRA,
      and ELISA were observed, and clinically ill patients had a wide range of antibody
      titers. Over a 30-day period, the percentage of positive responses did not
      change. Although multiple testing over several days enhanced the chance of
      confirmation, this difference was not significant. Combined results of the three
      assays enhanced the positive response to 83% of the total population (P < .005).
      These data demonstrate that there is no direct correlation between the positive
      response of these assays, and that clinically positive HIT patients can be missed
      by all three assays. With these limitations, the combination of platelet
      aggregation assay, SRA, and ELISA testing with multiple samples offers the best
      chance of confirming a positive HIT patient. Caution is advised, however, in
      interpreting all assay results, as no assay is optimal.

PMID- 9930562
TI  - Heparin-induced thrombocytopenia and the clinical use of low molecular weight
      heparins in acute coronary syndromes.
AB  - Standard unfractionated heparin has long been the mainstay of anticoagulant
      therapy. Despite its significant therapeutic benefits, unfractionated heparin has
      disadvantages in clinical usage, including the need for continuous intravenous
      infusion or multiple daily injections, and close laboratory monitoring of the
      activated partial thromboplastin time (aPTT) and/or plasma heparin
      concentrations, as well as risk for bleeding complications and heparin-induced
      thrombocytopenia (HIT). Low-molecular-weight (LMW) heparins have shown equivalent
      efficacy or superiority to unfractionated heparin, while permitting easier dosage
      and administration, and posing less risk for bleeding complications and HIT. A
      review of the clinical use of LMW heparins in acute coronary syndromes reveals a
      low incidence of HIT. However, LMW heparins are not recommended for the treatment
      of established HIT due to cross-reaction with 80% of antibodies generated during
      exposure to unfractionated heparin.

PMID- 9930563
TI  - Management of heparin-induced thrombocytopenia: a cardiovascular surgeon's
      perspective.
AB  - Three areas involved with heparin-induced platelet activation (HIPA) need to be
      discussed from a cardiovascular surgeon's perspective. These include the clinical
      presentation and management of HIPA-associated events, preparation for surgery in
      patients with existing HIPA, and medical-legal considerations surrounding HIPA
      associated events and treatment. The incidence of heparin-induced
      thrombocytopenia (HIT) is approximately 1% to 5% of surgical patients. As many as
      35% of these patients experience heparin-induced thrombocytopenia and thrombosis
      syndrome (HITTS), which generally results in devastating outcomes. The initial
      management of all patients with HIT and HITTS involves withdrawal of heparin.
      Thereafter, treatment of HITTS should include aggressive interventions with
      antithrombin agents, plasmapheresis, and possibly thrombolytic agents. Surgery
      for patients with existing HIPA needs to be carefully planned. Once all
      nonsurgical avenues have been explored, surgery should be performed following
      proper planning and education of patient and family. Finally, the number of
      lawsuits directly related to outcomes in cases involving HIT and HITTS is
      increasing. Cardiovascular surgeons should be well prepared, limiting their
      exposure to potential litigation with good clinical management and complete
      clinical and laboratory documentation.

PMID- 9930564
TI  - Antithrombin agents as anticoagulants and antithrombotics: implications in drug
      development.
AB  - The development of direct thrombin inhibitors goes back nearly four decades.
      Organic synthetic benzamidine derivatives were initially developed as direct
      antithrombin agents. Later, the structural analysis of fibrinogen, leading to the
      identification of thrombin cleavage sites, resulted in the recognition of
      specific peptide sequences where thrombin cleaved fibrinogen. These observations
      led to the development of synthetic peptide derivatives as inhibitors of
      thrombin. The leech salivary extract contained natural hirudin, the structural
      elucidation of which led to the development of a recombinant equivalent protein
      (r-hirudin). Understanding the biochemical actions of thrombin and the structure
      of various inhibitors prompted the development of hirulogs, a class of hybrid
      molecules with two sites of action. Currently, several of these thrombin
      inhibitors are being developed for various indications in both intravenous and
      subcutaneous protocols. The increased interest in thrombin inhibitors is also
      prompted by reports of heparin-induced thrombocytopenia (HIT) with heparin and
      the need to anticoagulate patients with alternate drugs. These agents produce a
      direct anticoagulant response by targeting thrombin. In addition, the
      amplification of the coagulation cascade by thrombin activation of factors V and
      VIII, stabilization of fibrin by activated factor XHI, and platelet activation is
      also inhibited by these thrombin inhibitors. Some of the synthetic thrombin
      inhibitors are also capable of inhibiting other enzymes in the coagulation
      cascade. Thrombin inhibitors therefore exert a complex effect on the coagulation
      network and should be carefully evaluated in clinical trials. These drugs can be
      used for prophylactic and therapeutic and surgical indications. However, the
      different thrombin inhibitors have shown distinct pharmacologic differences.
      There is now an interest in developing oral antithrombin inhibitors. Such issues
      as antagonism, laboratory monitoring, drug interactions, and long-term safety
      remain unresolved. Current research is focused on addressing these issues.

PMID- 9930565
TI  - The wide spectrum and unresolved issues of megaloblastic anemia.
AB  - Several fundamental questions relating to the biochemical basis of megaloblastic
      hemopoiesis in vitamin B12 (B12) and folate deficiency and neurological damage in
      B12 deficiency remain to be answered. Among them is the explanation underlying
      (1) the failure of B12-deficient animals to develop megaloblastic hemopoiesis
      despite indirect evidence of impaired thymidylate synthesis and (2) the inverse
      relationship between the extent of hematologic and neurological damage in B12
      deficiency. Diagnostic advances have led to the awareness that many patients with
      B12 or folate deficiency are hematologically normal and that subtle hematologic
      or neuropsychiatric manifestations may be found at a fairly early stage of
      developing B12 deficiency. Studies of the mechanism of absorption of B12 in food
      have identified the syndrome of food B12 malabsorption in which the degree of B12
      deficiency is commonly, although not invariably, mild. Folate intake influences
      the prevalence of neural tube defects (NTDs) and a suboptimal folate status may
      be associated with an increased risk for dysplasia and cancer. The latter may be
      at least partly the result of uracil misincorporation into DNA and consequent DNA
      strand breaks. Folate status has also been linked to arteriosclerotic vascular
      disease through its effect on serum homocysteine levels. Uracil misincorporation
      into DNA and increased serum homocysteine levels may also be found in B12
      deficiency. These adverse associations form the basis of a case for improving B12
      or folate status in individuals with a mild degree of deficiency. Because
      inadequate folate intake is relatively common, especially in the elderly and the
      poor, the fortification of staple foods with folate is currently under active
      consideration.

PMID- 9930566
TI  - Cobalamin and folate deficiency: acquired and hereditary disorders in children.
AB  - This review highlights the features of cobalamin and folate deficiency and
      insufficiency that are particular to children. Maternal deficiency of cobalamin
      and insufficiency or deficiency of folate are the principal causes of
      deficiencies of these vitamins in the newborn. Maternal cobalamin deficiency can
      be caused by pernicious anemia or postgastrectomy, but most often results from a
      diet lacking in animal protein. The mothers are usually not anemic and failure to
      thrive and neurological deficits are more common in their infants than is
      megaloblastic anemia. Inborn errors of cobalamin transport and metabolism present
      with homocystinuria and methylmalonic aciduria, either alone or in combination.
      They share many of the clinical features of nutritional cobalamin deficiency.
      Maternal folate insufficiency results in neural tube defects, fetal loss,
      prematurity, and fetal growth retardation. Inborn errors of folate metabolism are
      rare, but polymorphisms affecting the gene for methylenetetrahydrofolate
      reductase (MTHFR) are common and may have significant health implications.
      Elevation of plasma methylmalonic acid (MMA) levels reflects a functional lack of
      cobalamin, whereas elevated total homocysteine levels are associated with a lack
      of either folate or cobalamin. The determination of these should be part of the
      investigation of failure to thrive, neurological disorders, and unexplained
      anemia or cytopenias in children.

PMID- 9930567
TI  - Modern clinical testing strategies in cobalamin and folate deficiency.
AB  - Folate or cobalamin deficiencies are usually detected by hematologic
      abnormalities, such as a macrocytic megaloblastic anemia, or often milder signs,
      such as hypersegmented neutrophils. In fact, these vitamin deficiencies may be
      associated with clinical conditions in which anemia and/or macrocytosis are
      absent, such as neuropsychiatric disorders and inborn errors of folate or
      cobalamin metabolism. A battery of sensitive tests, including blood vitamin
      levels, serum methylmaIonic acid and homocysteine assays, and the deoxyuridine
      suppression test in the bone marrow, allows for early detection of vitamin
      deficiency. Additional tests may be included to identify the causes of
      deficiency, such as the Schilling test using crystalline cyanocobalamin, or a
      modified Schilling test for showing food cobalamin malabsorption. Strategies for
      diagnosing a vitamin deficiency differ according to the hematologic and clinical
      presentations. The deleterious effects (aside from anemia) that arise from
      cobalamin or folate deficiency and include neurological complications, increased
      risk of vascular disease due to hyperhomocysteinemia, and increased risk of some
      types of cancer related to folate deficiency, underscore the importance of making
      an early diagnosis and instituting treatment with the appropriate vitamin in
      preventing permanent damage.

PMID- 9930568
TI  - Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other
      manifestations of dysfunctional folate status.
AB  - Folate plays a key role in nucleic acid synthesis. As a consequence, the most
      conspicuous complication of folate deficiency or of derangements of folate
      metabolism is megaloblastic macrocytic anemia caused by interdiction of normal
      proliferation of rapidly dividing bone marrow cells. Other rapidly dividing
      cells, including those in the gastrointestinal tract, may also be affected by the
      megaloblastic process. This may result in malabsorption. However, there is
      mounting evidence to indicate that there are other earlier manifestations of
      folate deficiency or of longstanding suboptimal folate nutrition. Chief among
      these manifestations of folate deficiency are an increased predisposition to
      occlusive vascular disease and thrombosis, which have been linked to increased
      levels of homocysteine found in folate deficiency and abnormal states of folate
      metabolism. In addition, folate deficiency, previously considered free of
      neurological consequences, is now known to be associated with disturbances of
      mood, and even spinal cord syndromes similar to those seen in vitamin B12
      deficiency. Finally, there is both experimental and clinical evidence to suggest
      that folate deficiency may interfere with immunologic status and may be
      associated with an increased predisposition to neoplasia. Nutritional as well as
      genetic factors may contribute to these various nonhematological manifestations
      of folate insufficiency.

PMID- 9930569
TI  - Increasing the dietary intake of folate: pros and cons.
AB  - Studies providing unambiguous evidence that the occurrence and recurrence of
      pregnancies complicated by neural tube malformations were reduced by folic acid
      supplementation at the time of conception have prompted the Food and Drug
      Administration (FDA) to approve the fortification of cereal-grain products with
      this vitamin. Additional enthusiasm for this decision has emanated from studies
      that show an association of hyperhomocysteinemia with vascular disease and neural
      tube defects. Despite the apparent logic for the folic acid food fortification
      program, there are some concerns about the danger of such a policy to segments of
      the public who have unrecognized vitamin B12 deficiency because folate can mask
      the hematologic abnormalities and allow the neurological complications to
      progress or even accelerate. Thus, the apparent benefits of the folic acid
      fortification and the potential dangers of such a program have polarized opinions
      in favor of (pro) and in opposition to (con) this FDA policy. The purpose of this
      review is to present the evidence on which each of these two groups base their
      opinions.

PMID- 9930570
TI  - Cobalamin deficiency in patients infected with the human immunodeficiency virus.
AB  - Serum vitamin B12 levels are often low in human immunodeficiency virus (HIV)
      infected patients. However, only a few patients appear to have actual vitamin B12
      deficiency. A low red cell folate level accompanying the low vitamin B12 level
      makes the presence of vitamin B12 deficiency more likely. Our experience suggests
      that a low red cell folate level always indicates deficiency, but does not
      differentiate between vitamin B12 and folate deficiency. The deoxyuridine
      suppression test and the assay of serum or plasma total homocysteine and/or of
      methylmalonic acid levels can also be useful in the identification of patients
      with true vitamin B12 deficiency. HIV-positive patients frequently have
      absorption disorders, including vitamin B12 malabsorption. However, the
      correlation between vitamin B12 malabsorption and serum vitamin B12 and plasma
      homocysteine levels is poor. Abnormalities in vitamin B12-binding proteins, which
      are often found in HIV-positive patients, may explain many cases of low vitamin
      B12 levels. Current evidence suggests that low vitamin B12 levels are more common
      as the HIV disease progresses. The results of vitamin B12 treatment have been
      disappointing thus far, including the prevention of toxicity induced by
      azidothymidine. The possible role of vitamin B12 treatment in the long-term
      survival of HIV-infected patients is at present unknown. However, it is important
      to identify those patients who have real vitamin B12 deficiency to treat or
      prevent their hematologic and/or neurological symptoms.

PMID- 9930571
TI  - Ethnic and racial factors in cobalamin metabolism and its disorders.
AB  - A growing body of data indicates the importance of ethnic and racial factors to
      many clinical and scientific considerations of cobalamin metabolism and its
      disorders. Blacks have significantly higher cobalamin and transcobalamin
      (especially transcobalamin II) levels than whites. Because serum cobalamin levels
      are often influenced by factors unrelated to cobalamin intake, stores, or
      deficiency, it is unclear whether the differences in levels reflect cobalamin
      status or not. The ethnic differences, which are present in cord blood,
      childhood, and pregnancy as well, probably arise from combinations of hereditary
      and acquired causes. It also appears that blacks have lower homocysteine levels
      than whites, metabolize homocysteine more efficiently, and do not show the same
      benefit from vitamin therapy. Modern surveys indicate that pernicious anemia is
      as common in blacks and, perhaps, Asian Indians as in whites. Moreover, the
      disease appears to be accelerated in blacks and, to a lesser extent, Latin
      Americans. Yet, for various reasons, such as the blunting or absence of
      hyperbilirubinemia and the frequent coexistence of microcytic disorders,
      cobalamin deficiency may be more difficult to recognize in blacks. Many of these
      observations of differences and new-found similarities raise important clinical
      and public health issues. Does the standard reference range for serum cobalamin,
      derived largely from white subjects, promote underrecognition of deficiency in
      blacks with their higher cobalamin levels? Or does it promote overdiagnosis of
      cobalamin deficiency in many whites with their lower levels? Given their lower
      rate of neural tube defects, possibly lower homocysteine levels, more efficient
      homocysteine metabolism and lesser impact of vitamin therapy on it, does the
      untargeted promotion of high folate intake provide less benefit to blacks than to
      whites while exposing them to an equal risk for adverse effects because of
      unrecognized pernicious anemia?

PMID- 9930572
TI  - Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and
      immunohistochemical study of 18 cases.
AB  - Rhabdoid tumor is a well-accepted clincopathologic entity among childhood renal
      neoplasms; similar tumors have been described in extrarenal locations. We present
      the clinicopathologic profile and the immunohistochemical features of a series of
      soft tissue rhabdoid tumors. Twenty-eight cases coded as extrarenal rhabdoid
      tumor (ERRT), RT, possible ERRT, and "large cell sarcoma" were retrieved from the
      Armed Forces Institute of Pathology soft tissue registry. The tumors were
      reclassified according to strict criteria by light microscopy, clinical
      information, immunohistochemistry, and, in some cases, electron microscopy. Soft
      tissue rhabdoid tumor (STRT) was defined as (1) a tumor composed of noncohesive
      single cells, clusters, or sheets of large tumor cells with abundant glassy
      eosinophilic cytoplasm, an eccentric vesicular nucleus, and an extremely large
      nucleolus; (2) positivity for vimentin and/or cytokeratin or other epithelial
      markers by immunostaining; and (3) exclusion of other tumor types with rhabdoid
      inclusions (melanoma, other sarcomas, carcinoma). Eighteen cases met our criteria
      for soft tissue rhabdoid tumors. The median patient age was 13 years (range, 6
      months to 56 years). Ninety-four percent of STRT cases were positive for vimentin
      and 59% for pan-cytokeratin. Sixty-three percent and 60% were positive for CAM
      5.2 and EMA, respectively. Seventy-nine percent stained for at least one
      epithelial marker; 76% stained for both vimentin and epithelial markers
      simultaneously. Forty-two percent stained for MSA, and 14% for CEA and SMA. CD99,
      synaptophysin, CD57 (Leu-7), NSE, and focal S100 protein were identified in 75%,
      66%, 56%, 54%, and 31% of the STRT cases, respectively. All STRT cases examined
      were negative for HMB-45, chromogranin, BER-EP4, desmin, myoglobin, CD34, and
      GFAP. Follow-up examination in 61% of the STRT patients revealed that 64% of
      patients died of disease within a median follow-up interval of 19 months (range,
      4 months to 5 years); 82% had metastases to lung, lymph nodes, or liver; 22% had
      local recurrences before metastasis; and 18% were alive without known disease
      status (median, 5.5 years). Soft tissue rhabdoid tumor is a highly aggressive
      sarcoma, predominantly of childhood. Besides having nearly consistent
      coexpression of vimentin and epithelial markers, STRTs show positivity for
      multiple neural/neuroectodermal markers that overlap with those of primitive
      neuroectodermal tumor.

PMID- 9930573
TI  - Liver involvement by lymphoma: identification of a distinctive pattern of
      infiltration related to T-cell/histiocyte-rich B-cell lymphoma.
AB  - Liver biopsy specimens from 62 patients with hepatic infiltration by
      miscellaneous lymphomas were retrospectively studied. The most relevant
      histologic features of liver infiltration in the various subtypes of lymphomas
      were then compared. In this study, diffuse large B-cell lymphomas were the most
      common neoplasm to involve the liver as primary or secondary tumors (64.5% of
      cases). The next most common lymphoma to involve the liver was Hodgkin's disease,
      found in 19.4% of cases, followed by peripheral T-cell lymphomas (9.7%), follicle
      center cell lymphomas (4.8%), and primary hepatic marginal zone B-cell lymphoma
      of the mucosa-associated lymphoid tissue type (1.6%). Within the group of large B
      cell lymphomas, a particular subset of cases was found, which was identified as T
      cell/histiocyte-rich B-cell lymphoma. This rare variant of diffuse large B-cell
      lymphomas involves the liver in a very distinctive way that may mimic, on both
      clinical and histologic grounds, inflammatory liver disease or hepatic
      infiltration by Hodgkin's disease. Although these diagnostic ambiguities can be
      easily solved by current immunohistochemistry, awareness of these potentially
      misleading features is mandatory to avoid misdiagnosis.

PMID- 9930574
TI  - Breast carcinoma associated with necrotic granulomas in axillary lymph nodes.
AB  - From a series of 100 consecutive breast carcinomas with axillary lymph node
      metastases, two cases of necrotic granulomas in the nodes are presented. Lymph
      nodes in each case were characterized by areas of necrosis surrounded by a
      palisade of cells resembling histiocytes as seen in a rheumatoid nodule. Although
      the initial impression was that of a reactive granuloma, when immunostained for
      keratin and EMA, the areas of necrosis showed positive staining for keratin and
      EMA in a cytoplasmic pattern. The surrounding palisade of cells stained with
      histiocyte markers, while the necrotic area itself was negative. Staining for
      both estrogen and progesterone markers was also negative. Staining of nine lymph
      nodes with caseating granulomas not associated with carcinoma with the same panel
      of antibodies revealed no staining except for irregular, noncellular staining
      with EMA. This pattern of necrosis in axillary lymph nodes from two cases of
      breast carcinoma was interpreted as evidence of necrotic metastatic tumor cells.
      Necrosis in axillary lymph nodes associated with invasive breast cancer should
      arouse suspicion for metastasis.

PMID- 9930575
TI  - Diagnosis of malignant epithelial thyroid lesions: fine needle aspiration and
      histopathologic correlation.
AB  - Fine needle aspiration is a diagnostic tool useful as a guide to patient
      management. We believe that its role in solving the diagnostic dilemmas presented
      by thyroid nodules is still underappreciated. Current fiscal constraints in
      health care might bring about a wider use of this simple technique to select
      patients for surgery. Care in sampling a mass is essential to obtain aspirates
      that are representative of the lesion and adequate in quantity for
      interpretation. Several aspirates are needed from all but the smallest masses.
      Most thyroid carcinomas are well-differentiated with a low grade of malignancy.
      The majority of these are papillary carcinomas, which are easily diagnosed in
      good cytologic smears. With fine needle aspirates the goal is to diagnose a
      follicular neoplasm and to separate it from the adenomatoid nodule. The
      follicular neoplasm then can be classified as adenoma or carcinoma with the
      histologic sections. The minimally invasive carcinoma still can be challenging to
      recognize. We hope that the cytologic criteria and histopathologic correlations
      presented here will help general pathologists who interpret aspirates. We believe
      that in the near future additional immunohistochemical methods and genetic
      markers will be used increasingly to discriminate among the neoplasms and to
      provide prognostic information.

PMID- 9930576
TI  - Synovial sarcoma.
AB  - Synovial sarcoma is a rare soft tissue tumor of children and adults that is
      unrelated to synovium and can occur in almost any part of the body. The familiar
      biphasic synovial sarcoma has discernible glandular or solid epithelial
      structures, and monophasic forms have characteristic ovoid or spindle cells with
      only immunohistochemical or ultrastructural evidence of epithelial
      differentiation. There are several morphologic patterns, including myxoid and
      hemangiopericytic, and behaviorally distinct calcifying, ossifying, and poorly
      differentiated subtypes can be recognized. Most synovial sarcomas are
      immunoreactive for cytokeratin, epithelial membrane antigen, and bc12 protein,
      and negative for CD34, and many express S100 protein and CD99 (MIC2). Nearly all
      synovial sarcomas have a specific t(x;18) (p11.2;q11.2) chromosomal abnormality,
      resulting in fusion of either of two variants of the SSX gene with the SYT gene;
      the genetic features may relate to morphology and outcome. The differential
      diagnosis can include a wide range of spindled, polygonal, or round cell
      sarcomas. Clinically, there have been marked recent improvements in local control
      of disease and lesser ones in management of metastases. The pathology,
      differential diagnosis, and behavior of this unique tumor are reviewed.

PMID- 9930577
TI  - Penicillin at the beginning.

PMID- 9930578
TI  - Angiotensin II receptors in the human brain.
AB  - The distribution of angiotensin AT1 and AT2 receptors in the human central
      nervous system has been mapped and is reviewed here. The results discussed
      provide the anatomical basis for inferences regarding the physiological role of
      angiotensin in the human brain. The distribution of the AT2 receptor is very
      restricted in the human brain and shows a high degree of variability across
      species. The physiological role of this receptor in the adult central nervous
      system is not clear. In contrast, a high correlation exists between the
      distributions of AT1 receptors in the human and other mammalian brains studied.
      This pattern of distribution suggests that angiotensin, acting through the AT1
      receptor, would act as a neuromodulator or neurotransmitter in the human central
      nervous system to influence fluid and electrolyte homeostasis, pituitary hormone
      release and autonomic control of cardiovascular function.

PMID- 9930579
TI  - Regulation of angiotensin II type 1 (AT1) receptor function.
AB  - The type 1 angiotensin receptor (AT1) mediates the important biological actions
      of the peptide hormone, angiotensin II (AngII), by activating an array of
      intracellular signaling pathways. The unique temporal arrangement and duration of
      AngII-stimulated signals suggests a hierarchy of post-AT1 receptor binding events
      that permits activation of selective effector pathways. Moreover, it predicts
      that the coupling of AT1 receptors is tightly regulated, allowing cells to
      differentiate acute responses from those requiring longer periods of stimulation.
      Recent studies have concentrated on delineating the molecular processes involved
      in modulating AT1 receptor activity. In addition to AT1 receptor modification
      (phosphorylation), trafficking (internalization and degradation) and interaction
      with regulatory intracellular proteins, other processes may include receptor
      dimerization, cross-regulation by other receptor systems, and receptor
      isomerization between activated and non-activated forms. This review focuses on
      recent advances in this area of research, highlighting directions for future
      investigation.

PMID- 9930580
TI  - Angiotensin II: a reproductive hormone too?
AB  - It has long been known that angiotensin II (Ang II) can affect reproductive
      tissues such as the uterus. However, the existence of a local renin-angiotensin
      system (RAS) in female as well as male reproductive tissues is a relatively
      recent observation. Of great interest is the discovery that all components of the
      RAS are present in the ovary, that the ovary secretes components of the RAS into
      the bloodstream, and that the ovary itself is responsive to Ang II. Recent
      studies suggest that the primary role of Ang II in the ovary is to cause atresia
      in non-ovulatory follicles; however, there is also compelling data to suggest
      that Ang II facilitates ovulation. Male reproductive structures also contain all
      of the components of the RAS, gonadotropins regulate the activity of these
      components, and these tissues have Ang II receptors. Of great interest is the
      expression of testis-specific angiotensin-converting enzyme (ACE), which is
      located on germ cells. Recent studies using gene knock-out techniques indicate
      that testis ACE plays an important role in male fertility. However, the overall
      significance of the RAS for normal reproductive function remains questionable.
      There is now a body of evidence implicating the RAS in pathophysiologies
      associated with reproductive function, which gives rise to the possibility that
      drugs acting on the RAS might ameliorate some of these disorders. Considerable
      work remains to determine the role of Ang II in reproductive functions.

PMID- 9930581
TI  - Roles for adenosine A1- and A2-receptors in the control of thyrotrophin and
      prolactin release from the anterior pituitary gland.
AB  - Adenosine has been implicated in various aspects of pituitary function but little
      is known of its role in the regulation of thyrotrophin (TSH) release. This study
      examined the effects of adenosine deaminase (ADA, which provokes adenosine
      breakdown) and selective adenosine-receptor ligands on the secretion of
      immunoreactive (ir-) TSH and prolactin (PRL) by rat anterior pituitary segments
      in vitro. ADA (5 U/ml) stimulated the release of both hormones (P<0.01) as also
      did the selective adenosine A1-receptor antagonist, 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX, 0.1 & 1 nM, P<0.01); the responses to ADA were
      inhibited by an A1-receptor agonist, N6-cyclohexyladenosine (0.1-10 nM, P<0.01).
      A non-selective A1/A2-receptor agonist, N-cyclopropylcarboxamidoadenosine (1-100
      nM) had mixed effects on ir-TSH release. However, the A2A-receptor selective
      agonist, CGS 21680 (1-100 nM) increased ir-TSH (P<0.05) and ir-PRL release
      (P<0.01); its effects on ir-TSH were blocked by concentrations of DPCPX (100 nM,
      P<0.01) sufficient to antagonize A2-receptors. These data suggest that adenosine
      acts via A1-receptors to tonically suppress ir-PRL and ir-TSH release but that
      A2A-receptor activation enhances the release of both hormones.

PMID- 9930582
TI  - Expression of IGF-1, IGF-1 receptor and TGF-beta following balloon angioplasty in
      atherosclerotic and normal rabbit iliac arteries: an immunocytochemical study.
AB  - Growth factors have been implicated in the pathogenesis of restenosis (myointimal
      hyperplasia after coronary interventions). In this study, we examined the
      expression of insulin-like growth factor-I (IGF-1), IGF-1 receptor, and
      transforming growth factor-beta (TGF-beta) in atherosclerotic and normal rabbit
      iliac arteries following overstretch balloon angioplasty of the iliac arteries to
      create a vascular lesion. Animals were sacrificed at 0, 3, 7, 15 and 42 days post
      angioplasty. The iliac arteries were processed for immunocytochemical
      localization of IGF-1, IGF-1 receptor and TGF-beta using colloidal gold and the
      data were quantitatively analyzed. IGF-1, IGF-1 receptor and TGF-beta
      immunoreactivity were all significantly increased in atherosclerotic arteries
      compared to control at all of the time points examined. Following balloon
      angioplasty, the levels of IGF-1 and IGF-1 receptor increased significantly in
      both control and even further in hypercholesterolemic vessels. In control
      vessels, the IGF-1 levels returned to preintervention levels, while in
      atherosclerotic vessels, the levels of IGF-1 and IGF-1 receptor remained
      elevated. In addition, TGF-beta levels in control vessels showed an initial rise
      in the first week following injury but then returned to baseline levels. In
      contrast, atherosclerotic vessels demonstrated a sustained expression of TGF
      beta. Thus, IGF-1 and TGF-beta expression is different in normal vs.
      atherosclerotic vessels following vascular injury. The intensity of expression of
      IGF-1 and its receptor, which is not reduced at 42 days compared to 15 days
      following injury, support a role for IGF-1 in smooth muscle cell proliferation
      and migration. The sustained increase in TGF-beta could facilitate extracellular
      matrix (ECM) accumulation. Local vascular therapy that is directed towards
      modulating the effects of IGF-1 and TGF-beta could reduce restenosis.

PMID- 9930583
TI  - Plasma glicentin in diabetic and gastrectomized patients.
AB  - Recent successful synthesis of human glicentin prompted us to establish an
      immunoassay method for determination of human glicentin in plasma. Human
      glicentin in plasma was measured using a newly developed sandwich ELISA. The mean
      fasting levels of human glicentin were 18.6+/-2.4 and 19.7+/-2.1 pM in normal
      subjects and diabetic patients, respectively. In diabetic patients with renal
      failure, plasma glicentin was elevated, exceeding 100 pM. In normal subjects,
      plasma glicentin increased to a peak level of about 130 pM at 60 min after an
      oral glucose load, and then decreased. In patients who underwent gastrectomy,
      plasma glicentin rapidly increased to a peak of about 300 pM at 30 min after oral
      glucose load. In a patient with short bowel syndrome plasma glicentin did not
      change following an oral glucose load. These results correspond with previous
      findings for gut glucagon-like immunoreactive materials (GLI) or enteroglucagon.
      We conclude that glicentin is secreted from the small intestine in response to
      intraluminal glucose stimulation in humans.

PMID- 9930585
TI  - Pathophysiology of contrast media anaphylactoid reactions: new perspectives on an
      old problem.

PMID- 9930584
TI  - Pig splenic nerve: peptides derived from chromogranins by proteolytic processing
      during axonal transport.
AB  - We have investigated the proteolytic processing of chromogranin A, chromogranin B
      and NESP55 (a novel chromogranin-like protein) during axonal transport using pig
      splenic nerve as a model. We have also studied the presence of chromogranin
      derived peptides in the perfusate during electrical stimulation of this nerve.
      High-performance gel filtration chromatography followed by radioimmunoassay (RIA)
      revealed that chromogranins are proteolytically processed to varying degrees
      during axonal transport. For chromogranin A and NESP55, the precursor is still
      present in the proximal part of the nerve, whereas in the distal part and nerve
      terminals, intermediate-sized peptides and the free peptides GE-25 and GAIPIRRH
      dominate, respectively. For chromogranin B, the precursor has already been
      processed to an intermediate-sized peptide in the proximal part of the nerve,
      which is also present in the distal parts together with the free peptide PE-11.
      For chromogranin B and NESP55, only the free peptides PE-11 and GAIPIRRH, or in
      the case of chromogranin A, the free peptide GE-25 plus an intermediate-sized
      one, are released from the terminals into the splenic perfusate. These results
      demonstrate that chromogranins are processed to smaller peptides during axonal
      transport.

PMID- 9930586
TI  - Basidiomycete allergens.

PMID- 9930587
TI  - Novel CD4 and CD8 T-cell subsets.

PMID- 9930588
TI  - Detection of IgE antibody to a radiocontrast medium.
AB  - BACKGROUND: Very little is known about the mechanisms underlying adverse
      reactions to radiocontrast medium. On the basis of the clinical features of the
      adverse reactions, it has generally been considered that an IgE-dependent
      mechanism is not involved in these adverse reactions, and only a few studies have
      demonstrated the presence of IgE antibody to radiocontrast medium in patient
      sera. METHODS: We assayed for IgE antibody to ioxaglic acid (Hexabrix), a
      representative radiocontrast medium, in the sera of patients who had developed
      adverse reactions to ioxaglic acid. A conjugate was prepared by coupling succinyl
      ioxaglic acid to human serum albumin. Enzyme immunoassay and radioimmunoassay for
      the detection of IgE antibody to ioxaglic acid in patient sera were constructed
      by physical adsorption or by covalent coupling of the conjugate on solid
      supports. RESULTS: When the radioactivity or the absorbance exceeding the mean
      plus 3 SD for normal healthy subjects was regarded as positive, IgE antibody was
      detected in the sera of 47.1% of the patients who had a past history of adverse
      reactions to ioxaglic acid and 16.2% of those who had experienced adverse
      reactions to ioxaglic acid within 24 h before the blood collection, although the
      IgE antibody levels were low. On the other hand, IgE antibody to ioxaglic acid
      was not detected in the sera of patients with no history of adverse reactions to
      ioxaglic acid. Inhibition experiments revealed the presence of IgE antibody
      specific to ioxaglic acid in the serum defined as positive for IgE antibody to
      ioxaglic acid. The presence of IgE antibody to ioxaglic acid did not always
      correlate with the activation of mast cells due to the occurrence of adverse
      reactions to ioxaglic acid. CONCLUSIONS: A small amount of IgE antibody to
      ioxaglic acid was detected in the sera of some patients with a history of adverse
      reactions to ioxaglic acid, and these adverse reactions may be partly explained
      by the presence of IgE antibody in the serum of at least some patients.

PMID- 9930589
TI  - Allergen sensitization of asthmatic and nonasthmatic schoolchildren in Costa
      Rica.
AB  - The prevalence of asthma among schoolchildren in Costa Rica is very high -- at
      the level of 20-30% -- and the reason is still unknown. A group of children from
      our previous epidemiologic study was randomly selected in order to establish the
      relation between asthma symptoms and allergy sensitization to common allergens.
      Serum samples from children with and without asthma were analyzed for the
      presence of IgE antibodies to 36 different allergens, for the presence of IgE
      antibodies to a pool of 10 common allergens, and for total serum IgE. The most
      prevalent IgE antibodies were those to mite, cockroach, dog, and house-dust
      allergens with MAST pipettes for the serologic measurements. Positive reactions
      to house dust, mite, cat, and the two molds (Alternaria and Cladosporium), and
      food allergens such as egg white, peanut, and shellfish were significantly more
      prevalent among the asthmatics than the nonasthmatics. Sensitization was equally
      prevalent at different ages, but the house-dust, mite, cat, dog, cockroach,
      Alternaria, and egg-white allergens had sensitized boys more often than girls (P
      < 0.01). The result of the analysis of IgE antibodies to a pool of 10 common
      allergens by Phadiatop supported the MAST pipette results, showing allergen
      sensitization in 57.7% of the asthmatic children and 42.3% in the nonasthmatic
      group. The concentration of IgE was significantly higher among the asthmatic
      children (372.2 kU/l) than among the nonasthmatic children (249.1 kU/l) (P <
      0.00001). Parasitic infestations were not examined in this study, but in most of
      Costa Rica these have largely been eliminated and could not explain the high
      total IgE levels. Our data indicate that the very high prevalence of bronchial
      asthma in Costa Rican schoolchildren can be related to sensitization, especially
      to airborne indoor allergens such as those of mites, cockroaches, and dogs.

PMID- 9930590
TI  - Eosinophilic gastroenteritis and Anisakis.
AB  - BACKGROUND: The differential diagnosis of eosinophilic gastroenteritis (EG)
      includes, among other diseases, parasitic infections such as anisakiasis, which
      has acquired worldwide importance. METHODS: We reviewed all patients referred to
      our allergy service who had been diagnosed as having primary EG to determine the
      possible role of Anisakis simplex in the etiopathology of the disease. All
      patients (n = 10) were studied and diagnosed as having primary EG between 1989
      and 1996, inclusive. Two different groups of subjects were used as controls:
      group A (149 subjects without digestive disorder) and group B (10 subjects with
      digestive disorder different from EG). Cutaneous prick tests were performed with
      the main foods, aeroallergens, and commercial extract of A. simplex. Total and
      specific serum IgE was measured in all patients. Gastric or gut histologic
      specimens were re-examined in five cases. RESULTS: Peripheral eosinophilia was
      detected in 40% of the patients with EG, and sensitization to A. simplex was
      detected in 80% of these. In both control groups, the rate of sensitization to A.
      simplex was 10%. Sensitization to A. simplex in EG patients with respect to
      control groups A and B showed odds ratios (OR) of 36 and 40, respectively. In one
      case, serialization of the histologic section allowed us to observe a whole
      Anisakis larva. CONCLUSIONS: Immunologic methods to detect specific antibodies
      against Anisakis should be used routinely before diagnosing EG as primary
      disorder. Preventive measures are of capital importance.

PMID- 9930591
TI  - In vitro lymphocyte proliferation in the diagnosis of allergy to
      phenoxymethylpenicillin.
AB  - BACKGROUND: The aim of this study was to investigate in vitro lymphocyte
      proliferation in the diagnosis of allergy to phenoxymethylpenicillin (PcV),
      comparing chemically reactive PcV, added to cell cultures in unconjugated form,
      to a PcV-PLL (poly-L-lysine) conjugate as antigens. Side-chain specificity of
      lymphoproliferative responses was investigated with reactive benzylpenicillin
      (PcG) and bacampicillin. METHODS: Seventeen patients with a history of
      hypersensitivity reactions in connection with PcV treatment were studied by means
      of the lymphocyte transformation test (LTT), the radioallergosorbent test (RAST),
      skin tests (prick and intracutaneous), and oral challenge with PcV. LTT was also
      performed in 20 control subjects exposed to PcV therapeutically, and in eight
      subjects with occupational exposure to this penicillin. RESULTS: Nine patients
      had a positive in vivo test to PcV (five by oral challenge, three by
      intracutaneous test, and one by both tests), and six were challenge-negative.
      When reactive PcV was used as antigen in LTT, positive LTT responses were
      observed in five of the nine patients with a positive in vivo test, and two of
      them were also side-chain specific. Positive LTT responses with reactive PcV also
      correlated with a positive RAST in five of seven subjects. None of the six
      patients with a negative challenge test, and only one of the 28 controls showed a
      positive LTT result with reactive PcV. Thus, the specificity of LTT with reactive
      PcV was 96%. In contrast, when PLL-conjugated PcV served as antigen, four
      challenge-negative subjects and 11 controls were LTT-positive. CONCLUSIONS: The
      results of this study indicate that LTT with chemically reactive PcV could be
      useful as an in vitro complement in the diagnosis of PcV allergy and as a tool to
      reveal the side-chain specificity of peripheral blood lymphocytes. A positive LTT
      to PLL-conjugated PcV may be an indicator of immunization, but not necessarily
      allergy, to the penicilloyl structure.

PMID- 9930592
TI  - Blood eosinophils from asymptomatic allergics have a reduced capacity to produce
      oxygen-free radicals.
AB  - BACKGROUND: The eosinophil granulocyte is an inflammatory cell that plays an
      active part in diseases such as asthma and rhinitis. This study aimed to
      investigate oxidative metabolism by blood eosinophils taken from allergic
      rhinitis patients, asthmatics, and nonallergic controls before and during the
      birch-pollen season. METHODS: Twenty patients with allergy to birch pollen and
      seasonal symptoms of rhinitis, some of whom were also asthmatic, were followed
      before and during the birch-pollen season in Sweden. The cells were purified
      using a Percoll gradient and the MACS system. Eosinophil purity in all samples
      was > 95%. Oxidative metabolism was measured by a chemiluminescence (CL) assay,
      with luminol and lucigenin acting as enhancers, and PMA, serum-treated zymosan
      (STZ), interleukin (IL)-5, or RANTES as stimuli. RESULTS: The allergic subjects
      showed reduced luminol CL when activated before the season with PMA (P = 0.040)
      or STZ (P = 0.0055). This was not seen during pollen exposure. STZ-activated
      lucigenin CL was also reduced before the season (P = 0.0027). The reduction was
      most evident in the group with asymptomatic rhinitis. In terms of eosinophil
      stimulation, IL-5 and RANTES were equally effective in allergic and nonallergic
      subjects, both before and during the pollen season. CONCLUSIONS: Blood
      eosinophils from asymptomatic allergics may have a lower capacity to produce
      oxygen-free radicals than eosinophils from nonallergics.

PMID- 9930593
TI  - Environmental priming influences allergen-specific nasal reactivity.
AB  - BACKGROUND: Preceding mucosal response to one allergen leads to the priming of
      the nasal mucosal response to another allergen. This study aimed to determine
      whether environmental allergens, especially ubiquitous animal dander, can induce
      nasal priming. METHODS: We investigated 26 grass-pollen-allergic subjects with
      additional sensitization to other aeroallergens. We performed continuous allergen
      challenge for 2 h with 1500 Dactylis glomerata pollen/m3 in the Vienna challenge
      chamber. The nasal flow at 150 Pa was examined, and subjective scores were
      obtained every 15 min. Statistical analysis was calculated from the area under
      curve of nasal flow reduction by Student's t-test and the Mann-Whitney U-test.
      Alpha was 0.05. RESULTS: In subjects with positive cat-dander RAST (class of > or
      = 3), besides grass-pollen allergy, the specific nasal allergic reaction to
      Dactylis challenge was significantly pronounced (P < 0.01), and an earlier onset
      of reaction was evident. The same results were obtained with additional
      sensitization to dog dander (P < 0.05). Concomitant sensitization to mugwort also
      led to escalating symptoms (P < 0.05). CONCLUSIONS: These results indicate that a
      specific nasal allergic reaction is augmented by environmental priming caused by
      ubiquitous animal dander and possibly is influenced by the daily use of spices.

PMID- 9930594
TI  - Priming effect of RANTES on eosinophil oxidative metabolism.
AB  - BACKGROUND: RANTES has been shown to possess chemotactic activity for
      eosinophils, which have also been considered to play a role in allergic
      inflammation through reactive oxygen species. Thus, in this study, we examined
      the effect of RANTES on radical oxygen products from eosinophils. METHODS:
      Purified eosinophils by CD16-negative selection or an eosinophilic cell line (EoL
      1) were incubated with or without RANTES (2.5 x 10(-6) M). To the mixture of
      eosinophils and luminol, calcium ionophore (A23187) or opsonized zymosan (OZ) was
      added, and radical oxygen products were determined by luminol-dependent
      chemiluminescence for 600 s. RESULTS: Eosinophil-mediated radical oxygen products
      of untreated eosinophils produced with A23187 gave a peak value of 14.09 +/- 2.40
      (mean +/- SE, n = 12) relative light units (RLU) and an integrated value of
      3232.20 +/- 513.09 RLU. However, with treatment with RANTES, a peak value of
      18.66 +/- 2.40 RLU and an integrated value of 5301.05 +/- 561.02 RLU were
      obtained. Eosinophil oxidative metabolism-induced A23187 or OZ was apparently
      augmented by the preincubation with RANTES. In addition, the radical oxygen
      products of EoL-1 showed similar results. CONCLUSIONS: Thus, we concluded that
      RANTES may play an important role in the pathogenesis of allergic inflammation
      through its involvement in eosinophil activation, as evidenced by oxygen
      products, as well as in selective eosinophil infiltration as selective eosinophil
      chemoattractant.

PMID- 9930596
TI  - Recurrent respiratory tract infections during the first 3 years of life and atopy
      at school age.
AB  - BACKGROUND: The hypothesis that infections reduce the risk of atopy was
      investigated by estimating the association between recurrent respiratory tract
      infections during the first 3 years of life and atopy at school age. METHODS:
      According to surveys in three different areas of Norway, children were classified
      into three groups: asthma, wheeze without asthma (wheeze), and no asthma/no
      wheeze. The skin prick test (SPT) was conducted on a stratified random sample of
      children (n = 502). The outcome was at least one positive SPT. The exposure
      variable was retrospective parental report of respiratory tract infections during
      the first 3 years of life. RESULTS: Infections were negatively associated with
      atopy, crude odds ratio (cOR) = 0.3, 95% confidence interval (95% CI) 0.1-0.7, in
      the asthma group. A similar association was present in children with wheeze cOR =
      0.4 (95% CI 0.1-1.2). The number of siblings was not associated with atopy in any
      group. Infections remained negatively associated with atopy in children with
      asthma, aOR = 0.3 (95% CI 0.1-0.7), in a logistic regression model adjusting for
      confounding factors. A similar pattern was present in the wheeze group.
      CONCLUSIONS: Recurrent respiratory tract infections during the first 3 years of
      life are negatively associated with atopy at school age in children with asthma.

PMID- 9930595
TI  - In vivo and ex vivo inhibitory effects of loratadine on histamine release in
      patients with allergic rhinitis.
AB  - BACKGROUND: The aim of this study was to evaluate the in vivo and ex vivo effects
      of the H1-antagonist loratadine on histamine release. METHODS: The study was
      designed as a double-blind, crossover trial. Ten patients with allergic rhinitis
      due to Dermatophagoides pteronyssinus were treated with loratadine (10 mg daily
      p.o.) and with placebo for 1 week, with a 2-week interval between the two
      treatments. Nasal lavages with saline solution were done before and after
      challenge with the relevant allergen at the end of treatments with loratadine and
      placebo. Venous blood was taken after treatments, and basophil histamine release
      induced by anti-IgE (10 microg/ml), N-formyl-methionyl-leucyl-phenylalanine
      (fMLP, 1 microM), and Ca2+ ionophore A23187 (1 microM) was evaluated by an
      automated fluorometric method. RESULTS: Treatment with loratadine attenuated
      early antigen-induced nasal obstruction, rhinorrhea, and itching. Nasal symptoms
      were accompanied by a significant histamine release in the nasal lavages
      collected 5 min after stimulation when the patients received placebo (median 4
      ng/ml, range 1-28; P < 0.05). After treatment with loratadine, histamine release
      in the 5-min postchallenge lavages was almost abrogated (median 0.5 ng/ml, range
      0-3; P < 0.01 vs placebo). Median anti-IgE-induced histamine release from
      basophils was 41.9% (range 27.8-79.2) after placebo and 30.0% (range 1.7-73.3, P
      < 0.05) after loratadine. Active treatment exerted an inhibitory effect also on
      basophil histamine release induced by fMLP and Ca2+ ionophore A23187.
      CONCLUSIONS: Treatment for 1 week with loratadine reduces allergen-induced nasal
      symptoms and inhibits in vivo and ex vivo histamine release in patients with
      allergic rhinitis.

PMID- 9930597
TI  - Pertussis IgE and atopic disease.
AB  - BACKGROUND: Pertussis toxin (PT) stimulates IgE production in animals, and
      pertussis vaccination and whooping cough may have similar effects in man.
      METHODS: We analyzed IgE responses to PT (PT-IgE) in sera from children primarily
      immunized with three doses of either an acellular 2- or 5-component vaccine, or a
      whole-cell (Wc) pertussis vaccine, and in children after whooping cough. The
      study comprised 50 children with both atopic disease and positive skin prick
      test, 99 nonatopic controls, and 40 children with verified pertussis. RESULTS:
      Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera
      from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5
      years. At 7 months, PT-IgE was more common after vaccination with acellular (24%)
      than with the Wc vaccine (3%, P = 0.02). PT-IgE was also more common (P = 0.001)
      after vaccination in children classified as atopic (36%) than in the control
      group (10%). Thirty percent of the children with pertussis had PT-IgE, more often
      so in atopic than nonatopic children (P = 0.02). CONCLUSIONS: Transient
      production of PT-IgE seems to be common after primary pertussis immunization with
      acellular vaccines, and after whooping cough, particularly in atopic subjects.

PMID- 9930598
TI  - Blood eosinophils and serum IgE as predictors for prognosis of interferon-gamma
      therapy in atopic dermatitis.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) therapy has been reported to be
      effective in atopic dermatitis. However, IFN-gamma therapy in atopic dermatitis
      has not yet been well established. In this study, immunologic variables were
      evaluated as predictors for the prognosis of IFN-gamma therapy in atopic
      dermatitis. METHODS: Sixty-eight atopic dermatitis patients were each treated 18
      times with 2 x 10(6) units/m2 IFN-gamma. Blood IgE level, eosinophil percentage,
      eosinophil count, and levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10
      were investigated. According to clinical responses, patients were classified into
      three groups: patients with improved clinical severity scores of over 20% were
      included in group A; those with improved scores of 20% or less in group B; and
      those with no improvement in group C. RESULTS: Serum IgE levels and blood
      eosinophil percentages were the lowest in group A. Most atopic dermatitis
      patients with an eosinophil percentage over 9% and IgE level over 1500 IU/ml did
      not respond to IFN-gamma therapy. Initial IL-10 levels were the highest in group
      A. IL-4 levels in group A, and IL-5 and IL-10 levels in all groups were
      significantly decreased by IFN-gamma therapy. CONCLUSIONS: IFN-gamma therapy may
      be recommended for atopic dermatitis patients with blood eosinophil percentages
      less than 9% and serum IgE levels less than 1500 IU/ml.

PMID- 9930599
TI  - Sensory hyperreactivity--a possible mechanism underlying cough and asthma-like
      symptoms.
AB  - BACKGROUND: Investigations of patients referred for suspected asthma have
      revealed a little-known group with symptoms suggesting hyperreactive airways in
      whom provocation with methacholine does not lead to bronchial obstruction. The
      underlying mechanisms are not known, and no objective diagnostic method has been
      available. METHODS: Provocations by inhalation of capsaicin solutions in stepwise
      increasing concentrations were used. Ten patients with asthma-like symptoms after
      exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or
      demonstrable bronchial obstruction, were compared to 10 patients with verified
      bronchial asthma and 28 healthy controls. RESULTS: The patients with asthma-like
      symptoms reacted with cough in a dose-dependent way. The number of coughs was
      significantly greater than in asthmatic patients and healthy controls. The latter
      two groups did not differ significantly. CONCLUSIONS: The capsaicin provocation
      test may be a valuable method for showing not only a greater cough sensitivity,
      but also asthma-like symptoms. The pathophysiology underlying the symptoms may be
      related to increased sensitivity of free, overactive nerve endings in the
      respiratory mucosa. Therefore, we suggest that this overreaction in the lower
      airways be called "sensory hyperreactivity".

PMID- 9930600
TI  - The effect of dry heat on mite, cat, and dog allergens.
AB  - BACKGROUND: Various techniques have been tried in an attempt to reduce allergen
      levels in homes. This study investigated the effect of dry heat on mite, cat, and
      dog allergens. METHODS: Samples (50 mg) of Dermatophagoides pteronyssinus and D.
      farinae cultures, and of house dust rich in the major cat and dog allergens Fel d
      1 and Can f 1 were heated for 5, 10, 15, 30, and 60 min at 60 degrees, 80
      degrees, 100 degrees, 120 degrees, and 140 degrees C. Control samples remained at
      room temperature. Extracts were assayed with the appropriate two-site mono- or
      mono/polyclonal sandwich ELISA. RESULTS: For Der p 1, the breakdown was
      proportional to temperature and heating time; after 30 min at 120 degrees C,
      allergen levels were reduced to < 1% of control. Der p 2 was more heat stable,
      requiring 140 degrees C for 30-60 min to achieve > 99% reduction. D. farinae
      groups 1 and 2 allergens showed results similar to those obtained with D.
      pteronyssinus. In contrast, Can f 1 and Fel d 1 were considerably more
      thermostable, with 50% and 70%, respectively, of allergen remaining after 60 min
      at 140 degrees C. CONCLUSIONS: The effect of dry heat on allergens increased with
      increasing time and temperature, cat and dog allergens demonstrating greater heat
      resistance than mite allergens. Dry heating methods may represent an alternative
      technique for removal of mite allergens; however, the greater stability of Fel d
      1 and Can f 1 suggests that this procedure may not be appropriate for pet
      allergens.

PMID- 9930601
TI  - Occupational asthma caused by exposure to asparagus: detection of allergens by
      immunoblotting.
AB  - BACKGROUND: Vegetables of the Liliaceae family, such as garlic or onion, have
      been reported to cause occupational asthma. However, there are few data on
      adverse reactions to asparagus. We evaluated the role of asparagus as a cause of
      asthma in a patient with respiratory symptoms occurring at work (horticulture)
      and studied relevant allergens. METHODS: A 28-year-old man complained of
      rhinoconjunctivitis and asthma when harvesting asparagus at work. Eating cooked
      asparagus did not provoke symptoms. A positive skin test reaction was observed
      with raw asparagus, Alternaria alternata, and grass-pollen extracts. The
      methacholine test demonstrated mild bronchial hyperresponsiveness. The patient
      had an immediate asthmatic response after challenge with raw asparagus extract.
      Bronchial provocation tests with boiled asparagus, A. alternata, and control
      extracts were negative. Two unexposed subjects with seasonal allergic asthma did
      not react to the raw asparagus extract. RESULTS: The double-blind, placebo
      controlled food challenge with raw asparagus was negative. Serum asparagus
      specific IgE was 13.9 kU(A)/l. By SDS-PAGE immunoblot, at least six IgE-binding
      components, ranging from 22 to 73 kDa, were detected only in raw asparagus.
      CONCLUSIONS: We report a case of occupational asthma caused by asparagus
      inhalation, confirmed by specific bronchoprovocation. Immunoblot analysis showed
      that asparagus allergens are very labile and quite sensitive to heat
      denaturation.

PMID- 9930602
TI  - Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium.
AB  - BACKGROUND: True allergic reactions to iodinated radiocontrast media are rare,
      and only a few well-documented cases of delayed-type hypersensitivity reactions
      caused by contrast media have been described. METHODS: We report a 61-year-old
      patient in whom percutaneous transluminal coronary angioplasty (PTCA) was
      performed with iopamidol, a nonionic contrast medium. Seven days later, the
      patient developed generalized maculopapular exanthema. Repeated patch tests with
      several iodinated agents were performed. RESULTS: A first patch test with
      iopamidol was positive. Repetition of the patch tests showed positive results to
      iopamidol as well as to iohexol and ioversol, two other nonionic contrast media,
      but not to other iodinated substances. Three months later, PTCA was repeated, and
      iopamidol was used again. Despite premedication, pruritic macular exanthema
      developed 1 day later. Whether iopamidol or trometamol -- an additive substance
      in the contrast medium -- was causative could not be determined, since a third
      set of patch tests was negative. CONCLUSIONS: Delayed-type hypersensitivity
      reactions to iodinated contrast media are rare. We recommend that patients with
      delayed exanthematous reactions undergo patch or intradermal tests with different
      contrast media and their additives, and that readings be performed immediately
      and later at days 2 and 3.

PMID- 9930604
TI  - Journal impact factors.

PMID- 9930603
TI  - Oral allergy syndrome (OAS) to grapes.

PMID- 9930605
TI  - Mites in Jakarta homes.

PMID- 9930606
TI  - Anaphylaxis to pine nuts.

PMID- 9930607
TI  - Airborne contact dermatitis to latex.

PMID- 9930608
TI  - Can exposure to latex cause adhesion formation?

PMID- 9930609
TI  - Food allergy or scombrotoxin poisoning?

PMID- 9930610
TI  - Relative safety of meloxicam in NSAID-intolerant patients.

PMID- 9930611
TI  - Anaphylaxis to walnuts and pine nuts induced by ACE.

PMID- 9930612
TI  - Chronic "idiopathic" urticaria and hydatid disease.

PMID- 9930613
TI  - Terminology and concept representation languages: where are we?

PMID- 9930614
TI  - Syntactic-semantic tagging as a mediator between linguistic representations and
      formal models: an exercise in linking SNOMED to GALEN.
AB  - Natural language understanding applications are good candidates to solve the
      knowledge acquisition bottleneck when designing large scale concept systems.
      However, a necessary condition is that systems are built that transform sentences
      into a meaning representation that is independent of the subtleties of linguistic
      structure that nevertheless underly the way language works. The Cassandra II
      syntactic-semantic tagging system fulfills this goal partially. Within the GALEN
      IN-USE project, it is used to transform linguistic representations of surgical
      procedure expressions into conceptual representations. In this paper, the
      proctology chapter of the SNOMED V3.1 procedure axis was used as a testbed to
      evaluate the usefulness of this approach. A quantitative and qualitative analysis
      of the data obtained is presented, showing that the Cassandra system can indeed
      complement the manual modelling efforts being conducted in the GALEN-IN-USE
      project. The different requirements related to linguistic modelling versus
      conceptual modelling can partly be accounted for by using an interface ontology,
      of which the fine tuning will however remain an important effort.

PMID- 9930615
TI  - How knowledge drives understanding--matching medical ontologies with the needs of
      medical language processing.
AB  - In this article, we introduce a knowledge-based approach to medical text
      understanding. From an in-depth consideration of deep sentence and text
      understanding we distill basic requirements for an adequate knowledge
      representation framework. These requirements are then matched with currently
      available medical ontologies (thesauri, terminologies, etc.). A fundamental trade
      off is recognized between large-scale conceptual coverage on the one hand, and
      formal mechanisms for integrity preservation and conceptual expressiveness on the
      other hand. We discuss various shortcomings of the most wide-spread ontologies to
      capture medical knowledge in-the-large. As a result, we argue for the need of a
      formally sound and expressive model along the lines of KL-ONE-style
      terminological representation systems in the format of description logics. These
      provide an adequate methodology for designing more sophisticated, flexible
      medical ontologies serving the needs of 'deep' knowledge applications which are
      by no means restricted to medical language processing.

PMID- 9930616
TI  - Representation of change in controlled medical terminologies.
AB  - Computer-based systems that support health care require large controlled
      terminologies to manage names and meanings of data elements. These terminologies
      are not static, because change in health care is inevitable. To share data and
      applications in health care, we need standards not only for terminologies and
      concept representation, but also for representing change. To develop a principled
      approach to managing change, we analyze the requirements of controlled medical
      terminologies and consider features that frame knowledge-representation systems
      have to offer. Based on our analysis, we present a concept model, a set of change
      operations, and a change-documentation model that may be appropriate for
      controlled terminologies in health care. We are currently implementing our
      modeling approach within a computational architecture.

PMID- 9930617
TI  - A methodology for partitioning a vocabulary hierarchy into trees.
AB  - Controlled medical vocabularies are useful in application areas such as medical
      information systems and decision-support systems. However, such vocabularies are
      large and complex, and working with them can be daunting. It is important to
      provide a means for orienting vocabulary designers and users to the vocabulary's
      contents. We describe a methodology for partitioning a vocabulary based on an IS
      A hierarchy into small meaningful pieces. The methodology uses our disciplined
      modeling framework to refine the IS-A hierarchy according to prescribed rules in
      a process carried out by a user in conjunction with the computer. The
      partitioning of the hierarchy implies a partitioning of the vocabulary. We
      demonstrate the methodology with respect to a complex sample of the MED, an
      existing medical vocabulary.

PMID- 9930618
TI  - Nitric oxide synthase-containing neurons in the myenteric plexus of the rat
      gastrointestinal tract: distribution and regional density.
AB  - Nitrergic (NO) neurons play crucial inhibitory roles in the control of gut
      motility. Variations in the density of these neurons within the gastrointestinal
      tract (GI) may provide useful functional information, but, most surveys available
      have employed limited and/or highly localized samples. It remains unclear to what
      extent (a) NO neurons are concentrated disproportionately in particular GI
      regions, or (b) variations in NO cell number merely reflect changes in overall
      myenteric neuron density. This experiment surveyed the distributions of neuronal
      nitric oxide synthase-positive (NOS+) and other myenteric neurons in the GI
      tract, using immunohistochemical and Cuprolinic blue counterstaining techniques.
      Adjustable sampling grids superimposed on wholemounts were used to investigate
      the topographic patterns in the stomach (90 sampling sites; 45 per side) and
      proximal duodenum (63 loci). We present four major findings: First, variations
      were detected in the number of NOS+ neurons in specific regions of the stomach
      (e.g., corpus > antrum approximately equal to forestomach) and along both
      longitudinal (oral > anal) and circumferential (mesenteric > antimesenteric) axes
      in the duodenum. Second, the variations in NOS+ neuronal counts within each organ
      covaried with the total number of myenteric neurons at different locations
      (stomach, r=0.77; duodenum, r=0.59), suggesting that local myenteric plexus
      density is a factor determining NOS+ cell concentrations. Third, in contrast to
      such a principle of covariation within each organ, NOS+ neurons constituted a
      consistently smaller proportion of gastric (20%) than of duodenal (28%) myenteric
      plexus neurons, suggesting that a second principle controls the characteristic
      percentages of the myenteric plexus that express NOS in different organs. Fourth,
      the regional samples were used to extrapolate the overall number of NOS+ and
      total myenteric cells in the rat stomach (43,000; 217,000) and first 3.5 cm of
      the small intestine (29,000; 103,000). These results, taken together, also
      suggest that the surveying protocol used is capable of detecting subtle
      differences in cellular distributions, thus providing a practical strategy for
      investigating patterns of chemical phenotypes within the GI tract.

PMID- 9930619
TI  - Developmental changes of sugar occurrence and distribution in the rat
      submandibular and sublingual glands.
AB  - The developmental expression of salivary glycoconjugates was investigated in the
      rat submandibular and sublingual glands by conventional and lectin
      histochemistry. By the time of the first differentiation of secretory structures,
      in spite of similar morphological features, a different histochemical reactivity
      was detected, accounting for a relevant content of neutral glycoconjugates in the
      submandibular gland and the occurrence of both neutral and acidic glycoconjugates
      in the sublingual one. The use of lectins allowed the main changes of secretory
      components to be noted around gestational day 18. DBA and WGA lectins seemed to
      act as pre- and post-natal development markers while Con A lectin was indicative
      of post-natal differentiation. Taken together, data from lectin histochemistry
      indicated the transitional occurrence of glycoconjugates, probably involved in
      temporally restricted functions, as well as the co-existence of different
      secretory components that might also reflect maturational changes of single
      products.

PMID- 9930620
TI  - Development of glomerular synaptic complexes and immunohistochemical
      differentiation in the superficial dorsal horn of the embryonic primate spinal
      cord.
AB  - Development of glomerular synapses in the superficial dorsal horn has been
      studied in the embryonic macaque spinal cord using light and electron microscopic
      techniques including Golgi impregnation, 3H-thymidine radioautography and pre
      embedding immunohistochemistry of substance P (SP), calcitonin gene related
      peptide (CGRP), calbindin D-28 K (CB) and parvalbumin (PV). The study revealed
      that substantia gelatinosa cells of the primate dorsal horn are generated last,
      but unlike in rodents, synaptogenesis in this region starts at early embryonic
      (E) stages of the 165-day long gestation. Already by E30, both Type 1 (light) and
      2 (dark) dorsal root axons and their growth cones are identifiable within the
      oval bundle of His, before they form synaptic contact with their final target
      cells. Subsequently they invade the dorsal horn and enter the bisecting
      interfaces formed by orderly programmed cell death. Each type of scalloped
      (sinusoid) central primary afferent terminal (i.e. DSA, RSV and LDCV) have well
      defined pre- and post-synaptic specializations already by E40. Among the
      neuropeptides studied, SP appears first at E67 and CGRP at E70 in the lateral
      position but within a few days both of them are spread to the entire superficial
      dorsal horn. Both SP and CGRP are present in the thin dorsal root axons and their
      growth cones, giving rise to scalloped and simple axon terminals. PV is
      transiently present in the entire length of the thick dorsal root afferents
      before becoming concentrated in the synaptic boutons. CB is displayed mainly in
      neurons of the lamina I and III. Dendrites of CB-immunoreactive cells establish
      synaptic connection with each type of dorsal root afferents, including glomerular
      synaptic complexes. These data reveal that the superficial dorsal horn in the
      primate spinal cord develops its characteristic synaptic complexes much earlier
      in gestation than in any other mammalian species studied. Furthermore,
      characteristic cytological features of the prospective glomerular complex emerge
      before establishment of the final synaptic contacts.

PMID- 9930621
TI  - Organization of the disynaptic pathway from the anteroventral cochlear nucleus to
      the lateral superior olivary nucleus in the ferret.
AB  - The medial nucleus of the trapezoid body (MNTB) is one of three major nuclei of
      the superior olivary complex and provides an important inhibitory input from the
      contralateral ear to the lateral superior olivary nucleus (LSO) in the initial
      binaural pathway for coding interaural intensity differences. The major input to
      the MNTB from the contralateral anteroventral cochlear nucleus (AVCN) involves
      giant, calyx-like endings that have a one-to-one relationship with cells in the
      MNTB as confirmed in the ferret in this study. The main objective of the present
      study was to define the subsequent organization of projections from cells
      receiving these calyx-like endings. Several anatomical tracers (Phaseolus
      vulgaris leucoagglutinin, dextran-biotin, and biocytin) were used that are
      transported both anterogradely and retrogradely within neuronal projections in
      order to define the organization of MNTB connections with the LSO in the adult
      ferret. Analysis focused on determining the topography in both the transverse and
      longitudinal planes of the projections. Focal tracer injections in the LSO
      resulted in retrograde labeling of a long, narrow column of cells in the MNTB.
      The orientation and location of labeled cells was dependent on the medial-lateral
      position of the injection site. In the rostral-caudal dimension of MNTB, there
      was no such topographic relation between the injection site and the position of
      labeled cells. Labeled cells in the MNTB were distributed more or less evenly in
      a longitudinal column regardless of whether the injection site was restricted to
      the rostral, middle or caudal part of the LSO. In keeping with this pattern,
      tracer injections in the MNTB resulted in bands of labeled axons that distributed
      endings throughout the rostral-caudal axis of the LSO. These bands or sheets
      varied in medial-lateral position relative to the location of the injection site,
      but lacked any such rostral-caudal gradient. Thus, overall the MNTB-LSO
      projections have a convergent-divergent pattern of organization. While MNTB cells
      receive singular calyx-like endings from the AVCN, LSO cells receive projections
      from a long column of cells in the MNTB. Implications for processing interaural
      intensity differences are discussed.

PMID- 9930622
TI  - Anatomical distribution of beta-endorphin (1-27) in the cat brainstem: an
      immunocytochemical study.
AB  - Using an indirect immunoperoxidase technique, we studied the location of beta
      endorphin (1-27) fibres and cell bodies in the cat brainstem. The highest density
      of immunoreactive fibres was found in the lateral and medial parabrachial nuclei
      and in the locus coeruleus; a moderate density was observed in the periaqueductal
      gray and the central reticular nucleus, and a low density was observed in the
      interpeduncular nucleus, the nucleus incertus, the raphe pallidus nucleus, the
      paralemniscal reticular nucleus, the laterodorsal tegmental nucleus, the
      pericentral division of the dorsal tegmental nucleus and the lateral reticular
      nucleus. Immunoreactive neurons were observed in the superior central nucleus,
      the pericentral division of the dorsal tegmental nucleus, the interpeduncular
      nucleus, the nucleus incertus and the dorsal raphe nucleus. Our results point to
      a more widespread distribution of beta-endorphin (1-27)-immunoreactive perikarya
      in the cat brainstem in comparison with previous studies carried out in the same
      region of other mammals. The distribution of beta-endorphin (1-27)-immunoreactive
      fibres and perikarya is compared with the location of other neuropeptides in the
      cat brainstem. Moreover, our findings reveal that beta-endorphin (1-27)
      immunoreactive structures are widely distributed in the cat brainstem, suggesting
      that the peptide might be involved in several physiological functions.

PMID- 9930623
TI  - Electron microscopic data on the neurons of nuclei subpretectalis and posterior
      ventralis thalami. A combined immunohistochemical study.
AB  - The nucleus rotundus receives GABA-like immunoreactive fibres from the nuclei
      subpretectalis and postero-ventralis thalami. This result was confirmed by
      Phaseolus vulgaris leucoagglutinin (PhA-L) anterograde tracer and with electron
      microscopic (EM) gamma-aminobutiric acid (GABA)-immunogold staining. The detailed
      electron microscopic analysis of the structure of the neurons in these nuclei
      revealed that the neurons in the nucleus subpretectalis displayed GABA-like
      immunoreactivity. In the postero-ventral thalamic nucleus a group of neurons was
      GABA-positive. The surface of the neurons was covered both with numerous GABA
      negative and GABA-like immunoreactive terminals that established asymmetrical and
      symmetrical synapses, respectively, with the GABA-positive neurons. The GABA-like
      immunonegative terminals are supposed to be the axon terminals of the collaterals
      of tecto-rotundal fibres in the subpretectal nucleus and the collateral terminal
      branches of contralateral tecto-rotundal fibres in the postero-ventralis thalami.
      In both nuclei, the GABA-like immunoreactive terminals may be developed by the
      collaterals of local neurons that establish symmetrical synapses. In the
      Phaseolus lectin-stained preparations these terminals may be labelled. The
      morphological characteristics of the neurons in the subpretectal and partly, in
      the posteroventral nuclei are similar to those of interneurons (local circuit
      neurons) and the numerous asymmetrical and symmetrical axo-somatic synapses,
      respectively. But these neurons locate outside of their target nucleus, and exert
      their modulatory effect on rotundo-ectostriatal transmission. Also, a
      contralateral influence is present in the nucleus rotundus that may interact in
      the cooperation of the eyes. The neurons of the subpretectal and posteroventral
      nuclei, similarly to the neurons of isthmic nuclei, are a special group of
      modulatory neurons with effects at a distance.

PMID- 9930624
TI  - NADPH-diaphorase-positive neurons and pathways in the brain of the frog Rana
      esculenta.
AB  - We described the NADPH-diaphorase-containing neurons and fibres in the brain of
      the frog Rana esculenta. In the telencephalon stained cells occurred in the
      olfactory bulb, all subdivisions of the pallium, the diagonal band, the medial
      septum and the striatum. The olfactory glomeruli showed the most intense enzyme
      reaction. The neuropil of the accessory olfactory bulb was also heavily stained
      and this staining extended to the rostral diencephalon through the ventral
      lateral pallium. Fibre staining was less intense in the medial pallium and the
      medial septum. In the diencephalon, NADPH-diaphorase staining was concentrated in
      the middle third of this part of the brain. The stained cells were embedded in a
      dense network of thin, stained fibres and terminals in the lateral anterior and
      central thalamic nuclei. Faintly stained cells were present also in the posterior
      preoptic nucleus, anterior thalamic nucleus, nucleus of Bellonci, corpus
      geniculatum thalamicum and the suprachismatic nucleus. In the mesencephalon,
      heavily stained cells occurred in the nucleus profundus mesencephali,
      anterodorsal, anteroventral and especially in the posterodorsal tegmental nuclei.
      Neuronal staining was less intense in the optic tectum and the torus
      semicircularis. Thick, intensely stained fibres occupied the lateral part of the
      tegmentum and the 7th layer of the tectum. A loose network of thin fibres
      occupied the periventricular area and all tegmental nuclei. In the
      rhombencephalon, the reticular nuclei and the inferior raphe nucleus showed the
      most intense staining, while some cells in the nucleus of the solitary tract and
      the dorsal column nuclei were less intensely stained. Heavy staining of fibres
      was characteristic of the spinal trigeminal tract, the solitary tract and the
      reticulospinal pathway.

PMID- 9930625
TI  - Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.
AB  - The binding of corticosterone, dexamethasone and aldosterone was investigated in
      plasma and in homogenates of liver, kidney, brain, brown adipose tissue and
      visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and
      obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone
      binding globulin (CBG) accounted for most of the binding, whereas that of
      glucocorticoid and mineralocorticoid receptors was much lower. Plasma
      corticosterone levels increased in sham-operated and obviously decreased in the
      adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed
      decreased plasma CBG; in the obese, CBG levels were lower than in controls and
      were not affected by either surgery. No variation with obesity or surgery was
      observed either in dexamethasone or aldosterone binding, the latter being
      practically zero in most samples. When expressed per unit of tissue protein, CBG
      activity was maximal in adipose tissues, with lowest values in brain and liver.
      In lean rats, tissue CBG activity decreased with either surgical treatment; no
      changes were observed in the obese, which also had lower CBG tissue levels. The
      relative lack of changes in CBG of obese rats suggests that they have lost -- at
      least in part -- the ability to counter-modulate the changes in glucocorticoid
      levels through CBG modulation, thus relying only on the control of corticosterone
      levels. This interpretation agrees with the postulated role of CBG modulating the
      availability of glucocorticoids to target cells.

PMID- 9930626
TI  - Insulin increases liver protein phosphatase-1 and protein phosphatase-2C
      activities in lean, young adult rhesus monkeys.
AB  - Liver glycogen synthase activity is increased, and glycogen phosphorylase
      activity and glucose 6-phosphate content reduced by in vivo insulin during a
      euglycemic hyperinsulinemic clamp in lean young adult rhesus monkeys. To examine
      the mechanism of dephosphorylation of liver glycogen synthase and glycogen
      phosphorylase, the enzyme activities of protein phosphatase-1, protein
      phosphatase-2C, cAMP-dependent protein kinase, glycogen synthase kinase-3,
      protein kinase C and protein tyrosine kinase were determined before and after
      three hours of in vivo insulin in these same monkeys. The bioactivity of an
      inositol phosphoglycan insulin mediator (pH 2.0) and cAMP concentrations were
      also measured in the liver before and after insulin administration. Insulin
      caused significant increases in protein phosphatase-1 (p = 0.005) and in protein
      phosphatase-2C activities (p = 0.001). Insulin-stimulated minus basal bioactivity
      of the pH 2.0 insulin mediator was strongly inversely related to the insulin
      stimulated minus basal glucose 6-phosphate content (r = -0.93, p < 0.0001). These
      findings suggest that protein phosphatase-1 and protein phosphatase-2C may be
      involved in the mechanism of in vivo insulin activation of liver glycogen
      synthase and inactivation of liver glycogen phosphorylase.

PMID- 9930627
TI  - Lack of melatonin effects on insulin action in normal rats.
AB  - Despite a large number of studies, the role of melatonin on glucose metabolism is
      still controversial. The aim of the present work was to further characterize the
      effect of melatonin on insulin action during: i) intravenous insulin tolerance
      test performed at different times of the day using melatonin, a melatonin agonist
      (S-20304), a melatonin antagonist (S-20928) or in pinealectomized rats. ii)
      euglycemic-hyperinsulinemic clamp performed in melatonin agonist-treated as well
      as in pinealectomized rats. The fall in glycemia after the insulin injection was
      not significantly affected by melatonin and melatonin agonist (S-20304) at ZT6,
      nor by the melatonin antagonist (S-20928) at ZT13 nor in pinealectomized animals
      at ZT6 in comparison to their respective control. Acute treatment with S-20304 or
      chronic suppression of melatonin by pinealectomy did not significantly alter
      basal plasma glucose and insulin levels or hepatic glucose production and whole
      body or individual tissue glucose utilization. These data do not give support to
      a crucial role of melatonin on insulin action in normal rats.

PMID- 9930628
TI  - Indices of carbohydrate and lipid metabolism in vasopressin-replete and 
      deficient New Zealand genetically hypertensive rats.
AB  - Indices of carbohydrate and lipid metabolism were investigated in male New
      Zealand genetically hypertensive and normotensive rats. Cross-breeding of male
      rats of these strains with female Brattleboro diabetes insipidus rats also
      provided the opportunity to examine the metabolic impact of vasopressin and its
      deficiency in hypertensive and normotensive rats. Hypertensive and normotensive
      rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and
      their blood/plasma analysed for various indices of carbohydrate and lipid
      metabolism. Whilst each group of rats maintained fasted normoglycemia,
      hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic
      relative to normotensive counterparts. Moreover, hypertensive or normotensive
      vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete
      counterparts. In vasopressin-replete rats, the apparently improved insulin
      sensitivity in hypertension was associated with significant falls in plasma
      glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin
      deficient rats were hypoglucagonaemic relative to the vasopressin-replete group.
      These data demonstrate that independent of vasopressin status, hypertension in
      the New Zealand strain and the diabetes insipidus hybrid was associated with
      improved insulin sensitivity. However, endogenous vasopressin exercises an
      influential role in carbohydrate and lipid metabolism in normotensive rats.

PMID- 9930629
TI  - Insulin levels after portal and systemic insulin infusion differ in a dose
      dependent fashion.
AB  - The role of the liver in the regulation of systemic insulin levels is not well
      understood. The reported extraction rates vary between 0 to 85%, and extraction
      of a constant fraction of 50% of the portally delivered insulin is generally
      assumed. In the present study, we have investigated the role of the liver in the
      regulation of systemic insulin levels in the normal rat. Insulin was infused into
      the portal vein of conscious and freely moving rats in doses of 20, 40, 80
      pmol/min during 15 min to mimic the gradual release of insulin by the native
      endocrine rat pancreas. The profiles of plasma insulin and glucose levels in the
      systemic circulation were compared to those obtained after direct infusion into
      the systemic circulation. The effect of intraportal and direct systemic infusion
      on plasma insulin and blood glucose levels were virtually similar where 20
      pmol/min was applied. But, these effects were different if the dose was 40
      pmol/min, and this difference increased when the dose was increased to 80
      pmol/min, since hypoglycemia was less severe and normoglycemia was restored more
      rapidly with portal than with systemic infusion. Thus, our results show that the
      fraction of intraportally infused insulin reaching the systemic circulation
      decreases with higher doses of insulin. This suggests that the liver contains
      adaptable mechanisms to reduce the systemic insulin levels.

PMID- 9930630
TI  - Leptin and interleukin-6 in sepsis.
AB  - Both leptin and interleukin-6 (IL-6) are hypersecreted in acute critical illness,
      such as sepsis. Leptin is produced by adipocytes, it inhibits appetite and
      stimulates the sympathetic nervous system, thereby reducing adipose mass. IL-6 is
      produced by immune cells and adipocytes, it reduces the production of other
      inflammatory cytokines and stimulates release of acute phase proteins by the
      liver, participating in the control of inflammation. Leptin inhibits, whereas IL
      6 stimulates, the hypothalamic-pituitary-adrenal axis. While high IL-6 levels are
      associated with poor outcome in critically ill patients, the role of leptin in
      critical illness and its importance for survival are not known. To examine the
      relation between IL-6, leptin and cortisol in critical illness, we performed
      frequent 4 h plasma sampling in eight patients on day 1 of intensive care unit
      admission for acute sepsis. Sampling was repeated on days 3 and 5 in the five
      survivors. The levels of all three hormones were markedly elevated; there was a
      lack of the normal diurnal rhythmicity of leptin and IL-6 and a blunted diurnal
      rhythmicity of cortisol secretion. A strong negative correlation between mean 24
      h plasma IL-6 and leptin was revealed. Although such a relationship could
      possibly be explained by the negative and positive effects of cortisol
      hypersecretion on each hormone respectively, a negative correlation between
      leptin and cortisol was detected, whereas there was no significant correlation
      between IL-6 and cortisol. Mean IL-6 values were higher (1389.5+/-644.9 vs.
      658.8+/-250.5) and leptin levels were lower (2.73+/-1.1 vs. 26.5+/-11.6) in the
      non-survivors than in the survivors. These findings suggest that IL-6 is not the
      principal stimulus of leptin hypersecretion in critically ill patients with
      sepsis. The negative relation between IL-6 and leptin is of potential importance,
      as high IL-6 levels have been associated with poor outcome in critically ill
      patients, and relatively low leptin levels may impair sympathetic system and
      immune functions.

PMID- 9930632
TI  - Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent
      diabetic patients: evidence for central hypersensitivity to growth hormone
      releasing hormone and peripheral resistance to growth hormone.
AB  - The aim of this study was to assess the GH-IGFI axis, GH receptor availability,
      as reflected by the levels of GH-BP, and the amount of GH-dependent IGFBP-3 in
      adult IDDM patients with different degrees of metabolic control. Thus, 10 adult
      well-controlled IDDMs (HbA1 7.8 +/- 0.4%), 10 adult non-ketotic poorly controlled
      IDDMs (HbA1 13.3 +/- 7%) and 14 sex- and age-matched healthy controls were
      subjected to two intravenous GH-RH stimulation tests with 0.1 and 1.0 microg/kg
      body weight respectively, and a plasma IGF-1 generation test induced by the
      administration of hGH. Poorly controlled IDDM patients exhibited an exaggerated
      GH response to 1.0 microg/kg of GH-RH when compared to healthy control subjects.
      Low fasting plasma IGF-1 levels and a blunted IGF-1 response to exogenously
      administered hGH were also found in poorly controlled IDDMs when compared to the
      healthy control group. GH-BP levels were significantly lower in IDDMs than in
      normal controls, and correlated positively with the IGF-1 generation capacity
      after hGH. Serum IGFBP-3 levels measured by RIA were similar in IDDM and control
      groups. Good glycemic control for 5.7 +/- 0.9 months did not correct the above
      mentioned abnormalities of the GH-IGF-1 axis. Our findings suggest that IDDM is
      associated with a diminished availability of GH receptors and synthesis of IGF-1.
      GH might then increase as a compensatory mechanism, further down-regulating liver
      GH receptors, and thus perpetuating the initial abnormality.

PMID- 9930631
TI  - Comparative effects of the selective estrogen receptor modulators (-)-, (+)- and
      (+/-)-Z bisdehydrodoisynolic acids on metabolic and reproductive parameters in
      male and female rats.
AB  - Doisynolic acids are non-steroidal estrogenic compounds originally obtained from
      alkali fusion of estrone and equilenin. Z-bisdehydrodoisynolic acids (Z-BDDA)
      exhibit a low binding affinity accompanied by a disproportionately high biologic
      activity. Two experiments were designed to investigate the chronic effects of (+)
      , (-)- and (+/-)-Z-BDDA and (+)-17beta-estradiol (E2) in male and female rats.
      The (+)-, (-)- and (+/-)-forms Z-BDDA were prepared and injected, daily for four
      to six weeks into male and female rats and changes in body weight, food intake,
      metabolic parameters, and reproductive parameters were investigated. Results from
      both experiments demonstrate that in male and female rats, (+)- and (+/-)-Z-BDDA
      had similar estrogenic effects on reproductive organ weight. Surprisingly, (-)-Z
      BDDA did not induce the increase in uterine weight observed with (+)- and (+/-)-Z
      BDDA and E2, demonstrating selective estrogen receptor modulation (SERM).
      Beneficial metabolic effects, although compound- and gender-specific, included a
      significant weight repression, reduction in cholesterol, reduction in blood
      glucose, and positive alterations in body fat distribution. Future research
      defining the optimal dosages of (-)-Z-BDDA that will maximize beneficial effects
      and minimize undesirable effects on reproductive tissues will lead to more
      efficacious treatment options for endocrine-responsive conditions in males and
      females.

PMID- 9930633
TI  - Alternative strategies of opiate detoxification: evaluation of the so-called
      ultra-rapid detoxification.
AB  - This study was done in order to examine the hypothesis that so-called ultra-rapid
      opiate detoxification provides a mild, short, and safe withdrawal. A total of 22
      patients who were addicted to opiates exclusively underwent ultra-rapid
      detoxification. Each patient was pretreated with methadone. During general
      anesthesia lasting about six hours with methohexital or propofol, naloxone was
      administered with doubling of the dose every 15 minutes with a starting bolus
      dose of 0.4 mg. The total bolus dose of 12.4 mg, delivered within 60 minutes, was
      followed by a naloxone infusion of 0.8 mg/h until the next morning. On the day of
      anesthesia naltrexone (50 mg/d) treatment was initiated. When withdrawal symptoms
      occurred, specific medications, e.g., clonidine, were added. After determining
      baseline values, withdrawal symptoms were investigated during a further four
      weeks by means of established clinical scales. The results document marked
      withdrawal symptoms for at least one week after detoxification. The intensity of
      withdrawal symptoms during the first seven days of treatment was significantly
      (p<0.05) more marked than during baseline. None of the patients underwent a life
      threatening complication and only one patient failed to complete the
      detoxification procedure. Finally, about 75% of the patients could be referred
      for further treatment. In this study ultra-rapid detoxification provided a safe
      withdrawal procedure with high rates of completed withdrawals and referrals for
      further treatment, respectively. However, in contrast to previous reports, many
      patients suffered from middle-grade withdrawal symptoms over several days. Due to
      the risks of general anesthesia and the expense associated with this treatment,
      only patients addicted to opiates alone and for whom other detoxification
      strategies are unsuitable should undergo a ultra-rapid detoxification procedure.

PMID- 9930634
TI  - Has the time come to abandon prophylactic lithium treatment? A review for
      clinicians.
AB  - This review is based an relevant publications and addresses the following
      questions: Does lithium exert a recurrence-preventive, prophylactic action in
      manic-depressive illness? Has prophylactic treatment with anticonvulsants or
      antidepressants become preferable to lithium prophylaxis? Which drug or drugs
      should be first-choice prophylactic agent in bipolar and in unipolar manic
      depressive illness?

PMID- 9930635
TI  - Is anxious-agitated major depression responsive to fluoxetine? A double-blind
      comparison with amitriptyline.
AB  - Whether fluoxetine (FX) is effective in the treatment of anxious depression is
      still debated. In the present study, after one week of placebo (single blind),
      142 outpatients affected by major depression with relevant anxiety and agitation
      were randomly assigned (double blind) to either FX (20 mg/day) (n. 67) or
      amitriptyline (AM) (daily dose: 115+/-39.2mg) (n.75) for a period of 10 weeks.
      Between groups, the mean score of Hamilton Rating Scale for Depression (HRSD) was
      significantly different only after 3 weeks of treatment (AM 14.7+/-5.7 vs FX
      17.3+/-6.2 (p = 0.02), whereas at the end of the trial it was similar (AM 8.15+/
      6.9; FX 8.96+/-6.6). At each visit, no significant difference between groups was
      found regarding the scores of the HRSD items "psychic anxiety", "somatic
      anxiety", "agitation". Furthermore, the FIX treatment did not increase the scores
      of the items "suicide", "psychic anxiety", "somatic anxiety", "agitation" and
      "insomnia". These findings suggest that patients affected by major depression
      with anxiety and/or agitation were effectively and safely treated with FX without
      increasing risks.

PMID- 9930636
TI  - The use of parametric vs. nonparametric tests in the statistical evaluation of
      rating scales.
AB  - In psychiatric studies, treatment efficacy is usually measured by rating scales.
      These scales have ordinal (rank) level and the statistical evaluation of the
      scale scores should be performed with nonparametric rather than parametric tests.
      In recent years, nonparametric statistical procedures for repeated measures have
      been developed for the evaluation of clinical trials in psychiatry. To assess the
      frequency of application of nonparametric tests in psychiatric trials, an
      analysis was performed on all treatment studies with panic disorder patients (DSM
      III/III-R) that could be traced in the literature. This survey revealed that
      nonparametric tests were used in only 16.7% of all studies.

PMID- 9930637
TI  - Classification of observational data with artificial neural networks versus
      discriminant analysis in pharmacoepidemiological studies--can outcome of
      fluoxetine treatment be predicted?
AB  - For several years, there has been an ongoing discussion about appropriate
      methodological tools to be applied to observational data in
      pharmacoepidemiological studies. It is now suggested by our research group that
      artificial neural networks (ANN) might be advantageous in some cases for
      classification purposes when compared with discriminant analysis. This is due to
      their inherent capability to detect complex linear and nonlinear functions in
      multivariate data sets, the possibility of including data on different scales in
      the same model, as well as their relative resistance to "noisy" input. In this
      paper, a short introduction is given to the basics of neural networks and
      possible applications. For demonstration, a comparison between artificial neural
      networks and discriminant analysis was performed on a multivariate data set,
      consisting of observational data of 19738 patients treated with fluoxetine. It
      was tested, which of the two statistical tools outperforms the two other in
      regard to the therapeutic response prediction from the clinical input data.
      Essentially, it was found that neither discriminant analysis nor ANN are able to
      predict the clinical outcome on the basis of the employed clinical variables.
      Applying ANN, we were able to rule out the possibility of undetected suppressor
      effects to a greater extent than would have been possible by the exclusive
      application of discriminant analysis.

PMID- 9930638
TI  - Effects of acamprosate on psychomotor performance and driving ability in
      abstinent alcoholics.
AB  - The possible effects of acute and long-term treatment of the antidipsotropic
      agent acamprosate on psychomotor performance and driving ability were studied in
      a prospective open clinical trial involving 5 alcoholic patients without any
      clinical evidence for cognitive impairement. Acamprosate 1995 mg/day was given
      for 6 months for relapse prevention with all patients being abstinent throughout
      the study. No side effects were reported during treatment. Psychomotor
      performance and driving ability were assessed using the ART 90, a standardized
      and computerized neuropsychological test battery. A number of relevant subtests
      measuring peripheral vision, split attention, sensomotoric function, reaction
      time, stress resistance and the capacity to integrate information was used at
      study entry, 6 weeks and 6 months after onset of treatment. While in two subtests
      a moderate improvement in psychomotor performance was found, in most subtests no
      differences compared to baseline could be shown. The results of this pilot study
      do not indicate any impairment of psychomotor performance by acamprosate.

PMID- 9930639
TI  - Clozapine associated neutropenia and cytomegalovirus colitis.
AB  - Both diarrhea and colitis associated with clozapine have been reported. We
      present a case of clozapine-associated neutropenia complicated by cytomegalovirus
      colitis. The definitive diagnosis was suggested on biopsy which showed
      eosinophilic intranuclear inclusions suggestive of cytomegalovirus infection, and
      confirmed on immunohistochemistry. Neutropenia or agranulocytosis in association
      with clozapine treatment may be complicated by colitis. In such cases,
      investigations for cytomegalovirus may be indicated.

PMID- 9930640
TI  - Tranylcypromine abuse associated with an isolated thrombocytopenia.
AB  - The authors report a case of a 35-year-old woman with a known history of alcohol
      abuse, who developed a tranylcypromine abuse with up to 600 mg tranylcypromine
      daily. She developed a severe thrombocytopenia and secondly a delirious
      withdrawal syndrome. MAOI causing thrombocytopenia is reviewed and the
      prescription of tranylcypromine to patients with previous substance abuse is
      discussed.

PMID- 9930641
TI  - Risperidone-induced hepatotoxicity.

PMID- 9930642
TI  - Murine endothelia do not express MHC class II I-Ealpha subunit and differentially
      regulate I-Aalpha expression along the vascular tree.
AB  - Cellular elements of the vascular wall, such as endothelium (En) and smooth
      muscle cells/pericytes (SM/P) possess important immunologic properties. We have
      previously reported that murine brain microvessel En cells and SM/P express Major
      Histocompatibility (MHC) class II molecules and activate syngeneic CD4+ T cells
      in a class II dependent way. Herein we compare MHC class II expression on brain
      microvessel En to aorta large vessel En cells in order to explore the mechanisms
      of immune responses in brain tissue versus other peripheral tissues.
      Interestingly, we demonstrate that En cells from brain microvessel and large
      aortic vessel express the I-A but not the I-E subunit of MHC class II molecules.
      The expression of I-A class II molecules can be upregulated on brain microvessel
      and aortic En cells by interferon-gamma (IFN-gamma). Similarly, the expression of
      I-A, but not I-E, MHC class II molecules on brain microvessel endothelial cells
      was upregulated in the presence of activated T cells. Interleukin-10 (IL-10) was
      found to inhibit IFN-gamma-mediated upregulation of I-A class II molecule
      expression on aortic but not on microvessel En cells. Our data may indicate that
      some differences in organ-specific immune responses, are defined by local
      parameters, such as MHC distribution and regulation.

PMID- 9930643
TI  - Vasculogenesis from embryonic bodies of murine embryonic stem cells transfected
      by Tgf-beta1 gene.
AB  - Mouse embryonic stem (ES) cells transfected with a 1.7 kb cDNA of porcine
      transforming growth factor type beta1 (TGFbeta1), known as ES-T cells, were found
      to be able to differentiate in vitro into cystic embryonic bodies (EBs) with
      outspread tubular structures. Morphological analysis using light, phase-contrast
      and electron microscopes revealed that in culture, the EBs of ES-T cells
      initially developed some flat endothelial-like cells which further proliferated
      and migrated to form thread structures. At 8-10 days after EB formation, these
      thread structures further developed into net-like and tubular structures
      connecting directly to EBs. Immunofluorescent assays using antibodies against Flk
      1 and von Willebrand factor (vWF) indicated that these net-like and tubular
      structures of ES-T cells consisted of vascular endothelial cells. Further
      analysis by RT-PCR revealed that the EBs with tubular structures expressed the
      mRNA of other markers of vascular endothelial cells, including VE-cadherin and
      platelet-endothelial cell adhesion molecule (PECAM). Cells of hematopoietic
      origin were not detected on the outside of EBs by immunostaining using several
      antibodies specific for granulocytes, macrophages and lymphocytes as well as by
      benzidine staining for erythroid cells on the outside of EBs. Our data
      demonstrates that the transfer of TGFbeta1 into ES cells results in a significant
      vasculogenesis without concomitant hematopoiesis. ES-T cells could therefore
      provide an excellent model for studying blood vessel formation and vasculogenic
      and hematopoietic interactions.

PMID- 9930644
TI  - Cyclooxygenase expression in bovine aortic endothelial cells exposed to cyclic
      strain.
AB  - The aim of this study was to investigate the effect of cyclic strain on
      cyclooxygenase (COX)-1 and 2 expression in bovine aortic endothelial cells (EC).
      EC, subjected to 10% average strain at 60 cycle/min, were analyzed for induction
      of COX by Northern blot analysis and confirmed by analysis of promoter activity
      in transient transfection experiments. Exposure of EC to cyclic strain induced
      promoter activity and expression of COX-2 but not of COX-1. The extent of
      induction, however, was lower than that seen with stimulation of 12-O
      tetradecanoylphorbol-13-acetate (TPA) and/or lipopolysaccharide (LPS). These
      results demonstrate that, unlike shear stress, cyclic strain does not affect COX
      1 expression and is a weak inducer of COX-2 promoter activity in bovine aortic EC
      with minimal effect on mRNA expression.

PMID- 9930645
TI  - Thrombin stimulated reactive oxygen species production in cultured human
      endothelial cells.
AB  - In order to study the major cellular source of reactive oxygen species (ROS) in
      perturbed human endothelial cells (EC), the effect of thrombin, a phospholipase
      A2 activator, on cultured EC ROS generation has been investigated. EC were
      incubated with 0.1-1 unit/ml thrombin and cellular superoxide anion (O(-)2)
      release and hydrogen peroxide (H2O2) production measured. Thrombin exposure
      caused an elevation in EC O(-)2 release and H2O2 production. The effects of
      protein kinase C, arachidonic acid metabolism, NADPH oxidase, and phospholipase
      A2 inhibitors on thrombin-induced EC H2O2 production were examined. EC were
      exposed to 0.5 unit/ml thrombin and cellular H2O2 production measured in the
      presence and absence of the protein kinase C inhibitor, H-7; arachidonic acid
      metabolism inhibitors, indomethacin, nordihydroguaiaretic acid, and SKF525A;
      NADPH oxidase inhibitor, apocynin; and phospholipase A2 inhibitor, 4
      bromophenacyl bromide. All inhibitors, with the exception of H-7 and
      indomethacin, suppressed thrombin-induced EC H2O2 production. The pattern of
      effects of these metabolic antagonists on thrombin-induced EC ROS production is
      similar to that previously reported on ROS production in EC exposed to high low
      density lipoprotein levels, and in stimulated leukocytes. These findings further
      implicate NADPH oxidase as a major ROS source in EC.

PMID- 9930646
TI  - Multinucleated variant endothelial cells (MVECs) of human aorta: expression of
      tumor suppressor gene p53 and relationship to atherosclerosis and aging.
AB  - Multinucleated variant endothelial cells (MVECs) generally exist in
      atherosclerotic human aorta and even in nonatherosclerotic aorta. Because the
      number of nuclei is increased in every MVEC, and because DNA instability was
      suspected, a series of oncogene expressions was conducted to clarify the nature
      of nuclear abnormality. The tumor suppressor gene p53 was found to be
      specifically expressed in the multinuclei of MVECs, while double nuclei were
      sometimes positive, and mononuclear typical endothelial cells were always
      negative for p53. Polymerase chain reaction-single-strand conformation
      polymorphism (PCR-SSCP) revealed extra bands in exons 5 and 7 of the p53 gene,
      but no additional band in exons 6 and 8. In a BCL family, BCL-2 was coexpressed
      in one or two nuclei in the perinuclear space of the multinuclei of MVECs,
      whereas MCL-1, BCL-XS/L, and BAX were all negative, indicating that the BCL-2
      coding gene is expressed only in the corresponding one or two nuclei of the
      multinuclei. Another oncogene, c-MET (hepatocyte growth factor receptor), was
      universally expressed in either type of endothelial cells, but other oncogenes, k
      RAS and c-ERBB2, were not expressed in either type. MVECs were derived from human
      aorta and therefore non-tumorous somatic cells. No morphologic evidence of
      apoptosis was found. Although it is unclear that the extra bands came from the
      MVECs or just from ECs associated with atherosclerosis, combined
      immunocytological studies and PCR analysis suggest that MVECs express mutant type
      p53.

PMID- 9930647
TI  - Estrogen replacement modulates resistance artery smooth muscle and endothelial
      alpha2-adrenoceptor reactivity.
AB  - The purpose of this study was to evaluate the effects of estrogen replacement on
      ovariectomized rats on the reactivity to alpha2-adrenoceptor activation, and to
      analyze the role of the endothelium in modulating this response. Third order
      branches of the superior mesenteric artery from ovariectomized untreated (OvX)
      and estrogen-replaced (E2) Sprague-Dawley rats were cannulated and pressurized to
      50 mmHg. Under relaxed conditions (0.1 mM papaverine), there were no differences
      in lumen diameter. Intact vessels from E2 rats were unresponsive to clonidine
      (0.01-10 microM); incubation in indomethacin (1 microM), a cyclooxygenase
      inhibitor, produced intermediate constriction that was significantly augmented by
      L-NNA (0.3 mM), a NO synthase inhibitor, or by endothelial denudation.
      Conversely, intact vessels from OvX animals constricted to clonidine in a
      concentration-dependent manner. This effect was significantly diminished by
      endothelial removal or indomethacin, but was not affected by L-NNA. Yohimbine (1
      microM), an beta2 receptor antagonist, significantly diminished arterial
      sensitivity to, and efficacy of clonidine. These results suggest that estrogen
      replacement enhanced vasoconstriction induced by smooth muscle alpha2
      adrenoceptor activation, although this effect was obscured in intact vessels due
      to an overriding influence of endothelial dilator substances, primarily NO. In
      arteries from OvX animals, smooth muscle was less sensitive to alpha2 agonist
      stimulation, however, the release of a vasoconstrictor prostanoid from the
      endothelium was predominant, and induced significant vasoconstriction.

PMID- 9930648
TI  - A sensitive fluorometric assay for determining hydrogen peroxide-mediated
      sublethal and lethal endothelial cell injury.
AB  - A rapid and sensitive quantitative fluorometric assay was developed to measure
      the response of endothelial cells to hydrogen peroxide (H2O2). The response of an
      endothelial cell-derived cell line, EA-hy-926, or human umbilical vein
      endothelial cells to H2O2 was determined using calcein-AM, a dye which becomes
      fluorescent upon cleavage by intracellular esterase(s). The ability of the cells
      to take up and convert calcein-AM was measured directly in the wells of 96-well
      flat-bottomed tissue culture plates with cell monolayers using a computerised
      microplate fluorimeter, or in cell suspensions using flow cytometry. The results
      obtained by these techniques were compared with each other and with a standard
      51Cr release cytotoxicity assay. We found that calcein-AM is a highly sensitive
      probe for measuring H2O2-mediated cell injury, as it can not only detect the
      irreversible cytotoxicity measured by 51Cr release assay, but can also
      distinguish sublethal and reversible injury seen at low H2O2 concentrations.

PMID- 9930650
TI  - The Sec1p homologue Vps45p binds to the syntaxin Tlg2p.
AB  - SNAREs are compartmentally specific membrane proteins required for intracellular
      membrane fusion. Homologues of the Saccharomyces cerevisiae protein Sec1p
      interact with, and are likely to be involved in regulation of, the syntaxin
      family of SNAREs. In yeast there are 7 functionally distinct syntaxins but only
      four clearly identifiable homologues of Sec1p. One of these, Vps45p, is required
      for transport from Golgi to late endosomes, and has been implicated in the
      function of the late endosomal syntaxin Pep12p. However, there is evidence that
      not all the functions of Pep12p are equally dependent on Vps45p, and conversely
      that the phenotypes of vps45 mutants cannot be explained entirely by loss of
      Pep12p activity. We have recently characterised two yeast syntaxins which
      function in trans-Golgi or endosomal compartments, Tlg1p and Tlg2p. We show here
      that the principal binding site for Vps45p on intracellular membranes is provided
      by Tlg2p rather than Pep12p, and that Vps45p is required for stable expression of
      Tlg2p. Vps45p is also associated with Tlg1p as part of a triple complex
      containing both Tlg1p and Tlg2p. Since a deltavps45 deltatlg2 double mutant has a
      more severe vacuolar protein sorting defect than a deltatlg2 mutant, Vps45p
      cannot only interact with Tlg2p. It appears that the role of Vps45p in protein
      traffic is more complex than has previously been assumed.

PMID- 9930649
TI  - Role of tyrosine phosphorylation in thrombin-induced endothelial cell contraction
      and barrier function.
AB  - Thrombin-induced endothelial cell (EC) barrier dysfunction is highly dependent
      upon phosphorylation of serine and threonine residues present on myosin light
      chains (MLC) catalyzed by a novel EC myosin light chain kinase (MLCK) isoform. In
      this study, we examined the participation of tyrosine protein phosphorylation in
      EC contraction, gap formation and barrier dysfunction. We first determined that
      thrombin significantly increases protein tyrosine kinase activity and protein
      tyrosine phosphorylation in bovine pulmonary artery EC. Tyrosine kinase
      inhibitors, genistein and 2,5 DHC, reduced EC tyrosine kinase activities,
      however, only genistein significantly attenuated thrombin-mediated increases in
      albumin clearance and reductions in transendothelial electrical resistance.
      Similarly, genistein but not 2,5 DHC, decreased basal and thrombin-induced Ca2+
      increases and MLC phosphorylation in the absence of alterations in Type 1 or 2A
      serine/threonine phosphatase activities. Immunoprecipitation of the EC MLCK
      isoform revealed a 214 kD immunoreactive phosphotyrosine protein and genistein
      pretreatment significantly reduced MLCK activity in MLCK immunoprecipitates.
      Although thrombin induced the translocation of p60src from the cytosol to the EC
      cytoskeleton, a detectable increase in the level of MLCK tyrosine phosphorylation
      was not noted after thrombin challenge. Taken together, our data suggest that
      genistein-sensitive tyrosine kinase activities are involved in thrombin-mediated
      EC MLCK activation, MLC phosphorylation, and barrier dysfunction.

PMID- 9930651
TI  - Nucleocytoplasmic shuttling by protein nuclear import factors.
AB  - Protein nuclear import factors are not, in general, believed to function in the
      nuclear export of macromolecules and their reutilization therefore requires their
      recycling from the nucleus to the cytoplasm. Two possible mechanisms for
      recycling have been proposed. On the one hand, protein import factors such as
      importin beta and transportin (Trn) could continuously shuttle between cytoplasm
      and nucleoplasm. On the other hand, these proteins could penetrate into the
      nucleus only as far as the inner surface of the nuclear pore complex and then
      directly return to the cytoplasm. In this manuscript, we have used microinjection
      analysis in human cells, and in vitro nuclear assays, to demonstrate that
      importin beta, transportin and importin alpha are all nucleocytoplasmic shuttle
      proteins that efficiently enter and exit the cell nucleoplasm. In the case of
      transportin, we have mapped sequences required for nucleocytoplasmic shuttling to
      the carboxy-terminal 270 amino acids of this 890 amino acid import factor, thus
      demonstrating that nuclear export is independent of the amino-terminal Ran
      binding domain of Trn. We further show that Trn shuttling is independent of
      nuclear RNA transcription. Overall, these data suggest that nucleocytoplasmic
      shuttling is likely to be a general attribute of protein nuclear import factors.

PMID- 9930652
TI  - Assembly of Drosophila lamin Dm0 and C mutant proteins studied with the
      baculovirus system.
AB  - Despite extensive knowledge of the in vitro polymerization properties of nuclear
      lamins, it is still not well understood how the nuclear lamina assembles in vivo.
      To learn more about the relationship between in vitro and in vivo polymerization
      of nuclear lamins, we expressed Drosophila lamin Dm0, mutant proteins, having
      well defined alterations of their in vitro polymerization properties, in Sf9
      cells using the baculovirus system. All lamin Dm0 mutants assembled into
      fibrillar aggregates indistinguishable in morphology from those assembled by the
      wild-type protein. However, in contrast to wild-type lamin Dm0, mutant proteins
      were extracted with buffers of physiological ionic strength and pH containing
      Triton X-100. These results indicate that various types of lamin dimer-dimer
      interactions can be disrupted without affecting the morphology of the lamin Dm0
      polymer. However, all types of dimer-dimer interactions tested appear to be
      important for full polymer stability. In addition, we analyzed the polymer
      formation of two Drosophila lamin C mutants and found that a segment in the
      carboxy-terminal tail domain is required for assembly of lamin C paracrystals at
      the nuclear lamina.

PMID- 9930653
TI  - Effects of the myosin inhibitor 2,3-butanedione monoxime on the physiology of
      fission yeast.
AB  - F-actin and associated myosins are thought to take part in a wide range of
      cellular processes, like motility and contraction, polarized growth, and
      secretion. The reagent 2,3-butanedione monoxime (BDM) is a well characterized
      inhibitor of the contraction of vertebrate muscle that reversibly affects myosin
      function and influences the intracellular concentration of Ca2+. Here we describe
      the influence of BDM on growth and division of the fission yeast
      Schizosaccharomyces pombe. At concentrations from 1-30 mM, BDM gradually
      inhibited formation and growth of S. pombe colonies on agar plates, with a lethal
      effect at > or = 15 mM. In strains of S. pombe that were blocked by elevated
      temperature from entry into mitosis, drug treatment reversibly decreased
      microtubule-independent tip growth and septation, with an IC50 value around 12
      mM; nuclear division, on the other hand, was essentially unaffected by up to 15
      mM BDM. At 30 mM BDM the secretion of invertase, which required both F-actin and
      microtubules, was decreased to the same extent as that seen when cytochalasin D
      was used to disrupt F-actin. However, the actin cytoskeleton was insensitive to
      up to 10 mM BDM, while the actin patches lost their polar distribution at 20-30
      mM BDM. Cells treated with 5-20 mM BDM for 3 hours and then high pressure frozen
      did not show an accumulation of secretory vesicles. However, 10 mM BDM treatment
      disorganized the fungal cell wall, resulting in some unusually thick parts lying
      next to regions were the wall was almost absent. These defects could be rescued
      by incubating the cells in inhibitors of glucanases. Osmolytic stabilization with
      sorbitol rescued the effect of 15 mM BDM on colony survival, indicating that the
      secretion of wall components and/or wall-modifying enzymes may be the principal
      reason for cell death caused by BDM. Our results are consistent with the
      hypothesis that BDM influences actin-dependent processes in fission yeast and
      that actomyosin-dependent motility contributes to the secretory process of tip
      growth.

PMID- 9930655
TI  - Profilin is associated with the plasma membrane in microspores and pollen.
AB  - In higher plants, a large number of isoforms for the actin monomer-binding
      protein profilin have been identified, whereas other organisms express only few
      profilins. Furthermore, plant profilin isoforms are expressed in a tissue
      specific manner. These observations raise questions concerning functional and
      locational differences between isoforms of plant profilins. In this paper, we
      introduce three polyclonal antisera and one monoclonal antibody developed against
      purified pollen profilins from Zea mays and against recombinant maize profilin.
      Immunoblot analyses of native profilins and four recombinant maize pollen
      profilin isoforms show that three of the antibodies display a preference for
      certain isoforms. In situ immunofluorescence of pollen of Zea mays and two
      developmental stages of microspores of Betula pumila indicates that all
      antibodies label plasma membrane-associated domains. Thus, we show that at least
      some profilin isoforms are located at a distinct subcellular domain within
      developing microspores and, less distinctly, in mature pollen. This contrasts
      previously reported uniform distributions throughout the cytoplasm of mature
      pollen and pollen tubes. The results are discussed in light of the large number
      of profilins co-expressed in plants and with reference to accumulating evidence
      for functional differences between profilin isoforms.

PMID- 9930654
TI  - Caspase-3-induced gelsolin fragmentation contributes to actin cytoskeletal
      collapse, nucleolysis, and apoptosis of vascular smooth muscle cells exposed to
      proinflammatory cytokines.
AB  - Gelsolin, an 80 kDa actin-severing protein, has been recently identified as a
      substrate for the cell death-promoting cysteinyl protease caspase-3
      (CPP32/apopain/YAMA). We investigated the role of gelsolin and its cleavage
      product in apoptosis of vascular smooth muscle cells (SMC) induced by the
      proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor
      alpha (TNF-alpha). Treatment with a combination of IFN-gamma and TNF-alpha
      reduced viability of SMC in a time- and concentration-dependent manner.
      Immunoblotting revealed that SMC treated with the cytokines generated a 41 kDa
      gelsolin fragment. The gelsolin fragmentation required activation of caspase-3,
      as the caspase-3 inhibitor diminished cytokine-induced cell death as well as the
      fragmentation. Gelsolin cleavage was accompanied by a reduction in F-actin
      content and by a marked disruption of cell structure. Adenovirus-mediated
      transfection of this N-terminal gelsolin fragment into SMC altered cell
      morphology, reduced cell viability, increased the number of TUNEL-positive cells,
      and promoted internucleosomal DNA fragmentation. Compared to wild-type cells,
      gelsolin-deficient SMC showed resistance to apoptosis induced by the inflammatory
      cytokines. These results suggest a mechanistic role for gelsolin cleavage during
      SMC apoptosis, a process implicated in vessel development as well as stability of
      atherosclerotic plaque.

PMID- 9930656
TI  - Characterization of the gap junction protein connexin37 in murine endothelium,
      respiratory epithelium, and after transfection in human HeLa cells.
AB  - Affinity-purified antibodies to oligopeptides derived from two different regions
      of the carboxyterminus and cytoplasmic loop or to the last 103 C-terminal amino
      acids of mouse connexin37 (Cx37) were used to characterize expression of this gap
      junctional protein in endothelium of several murine tissues. Cx37 was expressed
      in endothelium of large blood vessels in brain, liver, kidney, spleen, heart, and
      lung, but not in capillaries. In addition, weak Cx37 immuno-signals were observed
      in lung respiratory epithelium of small bronchi and in alveolar epithelial cells
      of bronchioli. The ratios of Cx37 protein to Cx37 mRNA in adult and embryonic
      kidney as well as skin were 29-303-fold larger than in lung, suggesting that Cx37
      mRNA was translated at different efficiencies in kidney and skin versus lung.
      Cx37 protein was more abundant in embryonic kidney and lung than in the
      corresponding adult tissues. After differential centrifugation of plasma membrane
      fractions in sucrose gradients, we found that Cx37-containing gap junctions in
      lung were much smaller than Cx32 and Cx26 aggregates from liver. HeLa cells were
      transfected with mouse Cx37 cDNA. In these cells, mouse Cx37 protein was
      phosphorylated mainly at serine, less at tyrosine, and very little at threonine
      residues. Three conductance states were resolved at 110, 240, and 315 pS.

PMID- 9930657
TI  - Expression of protein kinase C gene family members is temporally and spatially
      regulated during neural development in vitro.
AB  - We used primary cultures of rat hippocampal neurons and PCC7-Mz1 cells to
      correlate the expression of the protein kinase C (PKC) gene family with specific
      events during neural differentiation. Multipotent PCC7-Mz1 embryonic carcinoma
      stem cells develop into a tissue-like pattern of neuronal, fibroblast-like and
      astroglial cells by all-trans retinoic acid (RA) treatment. Western blot analyses
      demonstrate that PKCalpha, betaI, gamma, theta, mu, lambda, and zeta were
      constitutively expressed but the expression of PKCbetaII, delta, epsilon, and eta
      was up-regulated three days after addition of RA when cells mature
      morphologically. While the protein levels of the PKC isoforms betaII, delta and
      eta decreased after d6, when the major phenotypical alterations of the developing
      neurons were completed, PKCepsilon expression remained at a high level.
      Immunofluorescence studies demonstrated that PKCalpha, lambda and zeta were
      constantly expressed in stem cells and the arising cell types. PKCdelta was
      detected in all differentiated cell types, whereby PKCbetaII, gamma, epsilon, and
      zeta were solely found in the neuronal derivatives with PKCgamma predominantly
      located in the nuclei. PKCeta was weakly expressed at the Golgi complex of stem
      cells but expanded throughout the entire somata of all developing neurons. In
      contrast, PKCbetaII was abundant only in the somata of a minor fraction of all
      neurons (approximately 2.5%). Also, PKCepsilon was exclusively synthesized by a
      subpopulation of neurons (40+/-5%), where it was localized in the somata and in
      the axons. PKCzeta was persistently expressed in two forms, the full-length
      PKCzeta and the constitutively active, proteolytic product PKMzeta, reasoning
      that permanent PKCzeta activity is important for PCC7-Mz1 physiology.
      Fractionation of extracts from undifferentiated and differentiating PCC7-Mz1
      cells revealed that the conventional cPKCalpha was partly and the cPKCbetaI and
      the novel nPKCs delta and epsilon were mainly membrane bound, implying that they
      were also in an active state. However, when using the PKC substrate MARCKS
      (myristoylated alanine-rich C kinase substrate) to monitor cellular PKC activity,
      we observed that activation of PKC by phorbol ester was required for complete
      MARCKS phosphorylation and its translocation from the membrane to the cytoplasm.
      Our data show that the cell type-specific expression, subcellular localization
      and activation of PKCs are regulated in an isoform-specific manner during
      neurogenesis suggesting that they are involved in the control of neural
      development and in particular in neuronal differentiation.

PMID- 9930658
TI  - Nitric oxide synthase expression in cervical spinal cord in sporadic amyotrophic
      lateral sclerosis.
AB  - Nitration of neurofilament (NF) has been implicated in the pathogenesis of
      amyotrophic lateral sclerosis (ALS). Evidence of such includes elevated 3
      nitrotyrosine levels in spinal cord tissue and localized nitrotyrosine
      immunoreactivity with neurofilamentous aggregates in cortical and spinal motor
      neurons. To determine if neuronal nitric oxide synthase (nNOS) and inducible NOS
      (iNOS) are the sources of nitric oxide in sporadic ALS (sALS), particularly
      through over-expression of the enzyme, steady-state mRNA levels of these isoforms
      were studied by in situ hybridization. Paraffin-embedded, archival cervical
      spinal cord tissues from 7 sALS and 6 control cases were used. 35S-labeled
      riboprobes were generated from partial cDNAs. Immunohistochemistry was utilized
      to confirm results of iNOS hybridization. We observed that nNOS mRNA was
      constitutively expressed in cervical spinal motor neurons. However, iNOS mRNA and
      iNOS immunoreactivity was not observed in ALS or control motor neurons. Our
      observations suggest that the source of nitric oxide is the endogenous nNOS.
      Together with the results from other immunohistochemical studies, we further
      hypothesize a possible role of translational deregulation of nNOS in sALS.

PMID- 9930659
TI  - Role of heparan sulphate proteoglycans in the regulation of human lactoferrin
      binding and activity in the MDA-MB-231 breast cancer cell line.
AB  - We previously demonstrated that lactoferrin increases breast cell sensitivity to
      natural killer cell cytotoxicity whereas haematopoietic cells are unaffected by
      lactoferrin. It has been described that lactoferrin binds to various
      glycosaminoglycans. Compared to haematopoietic cells, breast cancer cells and
      particularly the breast cell line MDA-MB-231, possess a high level of
      proteoglycans. Scatchard analysis of 125I-lactoferrin binding to MDA-MB-231 cells
      revealed the presence of two classes of binding sites: a low affinity site with a
      Kd of about 700 nM and 3.9 x 10(6) sites and a higher affinity class with a Kd of
      45 nM and 2.9 x 10(5) sites per cell. To investigate the potential regulation of
      lactoferrin activity by proteoglycans expressed on the MDA-MB-231 cells, we
      treated these cells with glycosaminoglycan-degrading enzymes or sodium chlorate,
      a metabolic inhibitor of proteoglycan sulphation. We showed that chondroitinase
      treatment has no effect, while heparinase or chlorate treatment significantly
      reduces both the binding of lactoferrin to cell surface sulphated molecules such
      as heparan sulphate proteoglycans (HSPG) and the affinity of lactoferrin for the
      higher affinity binding sites. The modulation of the lactoferrin binding was
      correlated with a decrease in lactoferrin activities on both MDA-MB-231 cell
      sensitisation to lysis and proliferation. Taken together, these results suggest
      that the presence of adequately sulphated molecules, in particular HSPG, is
      important for lactoferrin interaction and activity on the breast cancer cells MDA
      MB-231.

PMID- 9930660
TI  - Modulation of human endothelial cell proliferation and migration by fucoidan and
      heparin.
AB  - Fucoidan is a sulfated polysaccharide extracted from brown seaweeds. It has
      anticoagulant and antithrombotic properties and inhibits, as well as heparin,
      vascular smooth muscle cell growth. In this study, we investigated, in the
      presence of serum and human recombinant growth factors, the effects of fucoidan
      and heparin on the growth and migration of human umbilical vein endothelial cells
      (HUVEC) in culture. We found that fucoidan stimulated fetal bovine serum-induced
      HUVEC proliferation, whereas heparin inhibited it. In the presence of fibroblast
      growth factor-1 (FGF-1), both fucoidan and heparin potentiated HUVEC growth. In
      contrast, fucoidan and heparin inhibited HUVEC proliferation induced by FGF-2,
      but did not influence the mitogenic activity of vascular endothelial growth
      factor (VEGF). In the in vitro migration assay from a denuded area of confluent
      cells, the two sulfated polysaccharides markedly enhanced the migration of
      endothelial cells in the presence of FGF-1. Finally, a weak inhibitory effect on
      cell migration was found only with the two polysaccharides at high concentrations
      (> or = 100 micro/ml) in presence of serum or combined with FGF-2. All together,
      the results indicated that heparin and fucoidan can be used as tools to further
      investigate the cellular mechanisms regulating the proliferation and migration of
      human vascular cells. Moreover, the data already suggest a potential role of
      fucoidan as a new therapeutic agent of vegetal origin in the vascular endothelium
      wound repair.

PMID- 9930661
TI  - Crystallographic and mutational analyses of an extremely acidophilic and acid
      stable xylanase: biased distribution of acidic residues and importance of Asp37
      for catalysis at low pH.
AB  - Xylanase C from Aspergillus kawachii has an optimum pH of 2.0 and is stable at pH
      1.0. The crystal structure of xylanase C was determined at 2.0 A resolution (R
      factor = 19.4%). The overall structure was similar to those of other family 11
      xylanases. Asp37 and an acid-base catalyst, Glu170, are located at a hydrogen
      bonding distance (2.8 A), as in other xylanases with low pH optima. Asp37 of
      xylanase C was replaced with asparagine and other residues by site-directed
      mutagenesis. Analyses of the wild-type and mutant enzymes showed that Asp37 is
      important for high enzyme activity at low pH. In the case of the asparagine
      mutant, the optimum pH shifted to 5.0 and the maximum specific activity decreased
      to about 15% of that of the wild-type enzyme. On structural comparison with
      xylanases with higher pH optima, another striking feature of the xylanase C
      structure was found; the enzyme has numerous acidic residues concentrated on the
      surface (so-called 'Ser/Thr surface' in most family 11 xylanases). The
      relationship of the stability against extreme pH conditions and high salt
      concentrations with the spatially biased distribution of charged residues on the
      proteins is discussed.

PMID- 9930662
TI  - Systematic fold recognition analysis of the sequences encoded by the genome of
      Mycoplasma pneumoniae.
AB  - A robust tool for fold recognition was applied to the systematic analysis of the
      sequences below 200 residues encoded by the genome of Mycoplasma pneumoniae. The
      goal was to determine the additional information gain achievable in genome
      analysis by fold recognition, beyond the intrinsic limits of homology studies. A
      list of 124 sequences encoding for soluble proteins or domains not homologous to
      each other, or to proteins with known three-dimensional structure, was analyzed,
      resulting in significant Z scores for the energy of the structural models in 12
      of these cases. This result indicates that systematic application of fold
      recognition techniques to the analysis of structurally unassigned soluble
      proteins can lead to high-confidence structural predictions with an efficiency of
      about 10%, a relevant contribution besides the complementary approach of homology
      analysis. Four of the predictions presented include mapping of the putative
      active site of the target sequence and lead to the detection of probable
      catalytic and binding residues. The data are discussed with reference to the
      functional implications of the structural models and to the results reported for
      the homologous genome of Mycoplasma genitalium.

PMID- 9930663
TI  - Use of propensities of amino acids to the local structural environments to
      understand effect of substitution mutations on protein stability.
AB  - Advances in site-directed mutagenesis and other genetic engineering techniques
      have made it possible to create novel proteins of interest. A challenging aspect
      of these studies is to understand the effect of substitution mutations on folding
      and stability of natural proteins. We present an analysis of protein structure
      data, available from the literature, for which substitution mutations have been
      made and changes in stability characteristics are reported. Amino acid structural
      environment parameters have been computed for a set of 304 non-homologous best
      resolved protein structures. The structural environment parameters were used to
      calculate each of the 20 amino acid propensities to a given structural
      environment. The observed increase or decrease in stability upon mutation was
      found to be correlated with the average residue structural environment propensity
      of wild-type residue versus mutant residue. The analysis presented here helps
      identification of less optimally placed residues in a given protein structure,
      and suggests possible substitution mutations to a residue with higher propensity
      to the corresponding local structural environment. We propose that such
      substitution mutations, suggested based on amino acid propensities to local
      structural environments, should bestow higher stability to the protein structure.

PMID- 9930664
TI  - Simple conformation space search protocols for the evaluation of
      enantioselectivity of lipases.
AB  - Two computational protocols have been evaluated regarding their ability to
      reproduce the enthalpic part of lipase enantioselectivity by forcefield potential
      energy differences (deltaV#R-S). Though the shortcomings of the approach are
      numerous, good qualitative results have been obtained here and elsewhere. The
      anticipated improvement of quantitative results by use of a second protocol,
      which did not impose any atom movement restrictions on the total system, was
      realized only in part. Seemingly, results depended not only on the design of the
      computational procedure but also on the enzyme-substrate combination modelled.
      With Candida antarctica lipase B, results diverged significantly more from an
      estimated deltadeltaH#R-S than with Rhizomucor miehei lipase and cutinase.

PMID- 9930665
TI  - Sequence properties of GPI-anchored proteins near the omega-site: constraints for
      the polypeptide binding site of the putative transamidase.
AB  - Glycosylphosphatidylinositol (GPI) anchoring is a common post-translational
      modification of extracellular eukaryotic proteins. Attachment of the GPI moiety
      to the carboxyl terminus (omega-site) of the polypeptide occurs after proteolytic
      cleavage of a C-terminal propeptide. In this work, the sequence pattern for GPI
      modification was analyzed in terms of physical amino acid properties based on a
      database analysis of annotated proprotein sequences. In addition to a refinement
      of previously described sequence signals, we report conserved sequence properties
      in the regions omega - 11...omega - 1 and omega + 4...omega + 5. We present
      statistical evidence for volume-compensating residue exchanges with respect to
      the positions omega - 1...omega + 2. Differences between protozoan and metazoan
      GPI-modification motifs consist mainly in variations of preferences to amino acid
      types at the positions near the omega-site and in the overall motif length. The
      variations of polypeptide substrates are exploited to suggest a model of the
      polypeptide binding site of the putative transamidase, the enzyme catalyzing the
      GPI-modification. The volume of the active site cleft accommodating the four
      residues omega - 1...omega + 2 appears to be approximately 540 A3.

PMID- 9930666
TI  - Molecular modelling of the ORL1 receptor and its complex with nociceptin.
AB  - The opioid receptor like (ORL1) receptor is a G-protein coupled receptor
      superfamily, and regulates a plethora of neurophysiological functions. The
      structural requirements for receptor activation by its endogenous agonist,
      nociceptin (FGGFTGARKSARKLANQ), differ markedly from those of the kappa-opioid
      receptor and its putative peptide agonist, dynorphin A (YGGFLRRIRPKLKWDNQ). In
      order to probe the functional architecture of the ORL1 receptor, a molecular
      model of the receptor has been built, including the TM domain and the extra- and
      intracellular loops. An extended binding site able to accommodate nociceptin-(1
      13), the shortest fully active analogue of nociceptin, has been characterized.
      The N-terminal FGGF tetrapeptide is proposed to bind in a highly conserved
      region, comprising two distinct hydrophobic pockets in a cavity formed by TM
      helices 3, 5, 6 and 7, capped by the acidic second extracellular (EL2) loop
      controlling access to the TM elements of the peptide binding site. The nociceptin
      conformation provides for the selective preference of the ORL1 receptor for
      nociceptin over dynorphin A, conferred by residue positions 5 and 6 (TG versus
      LR), and the favourable interaction of its highly positively charged core
      (residues 8-13) with the EL2 loop, thought to mediate receptor activation. The
      functional roles of the EL2 loop and the conserved N-terminal tetrapeptide opioid
      'message' binding site are discussed in the context of the different structural
      requirements of the ORL1 and kappa-opioid receptors for activation.

PMID- 9930667
TI  - Domain swapping in G-protein coupled receptor dimers.
AB  - Computer simulations were performed on models of the beta2-adrenergic receptor
      dimer, including 5,6-domain swapped dimers which have been proposed as the
      active, high affinity form (here the dimer interface lies between helices 5 and
      6). The calculations suggest that the domain swapped dimer is a high energy
      structure in both the apo dimer and in the presence of propranolol. In the
      presence of agonist the energy of the domain swapped dimer is significantly
      lowered. Analysis of the dimer structure suggests that the agonist-induced
      conformational change optimizes the helix-helix interactions at the 5-6
      interface. An antagonist on the other hand has little effect on these
      interactions. These observations are consistent with the hypothesis that the
      agonist functions by shifting the equilibrium in favour of the domain swapped
      dimer. Indirect support for the domain swapping hypothesis was obtained from the
      correlated mutations amongst the external residues of the known beta2-adrenergic
      receptors. These occur mainly at the 5-6 interface at precisely the locations
      predicted by the simulations; site-directed mutagenesis data in support of a
      functional role for these lipid-facing correlated residues is presented. The
      article includes a review of the experimental evidence for G-protein coupled
      receptor dimerization. Many other aspects of G-protein coupled receptor
      activation are discussed in terms of this domain swapping hypothesis

PMID- 9930668
TI  - Structural model of the catalytic domain of an enzyme with cell adhesion
      activity: human vascular adhesion protein-1 (HVAP-1) D4 domain is an amine
      oxidase.
AB  - Human vascular adhesion protein-1 (HVAP-1) is a multifunctional protein having at
      least two different cellular roles, functioning both as a lymphocyte-endothelial
      cell adhesion protein and as an enzyme with monoamine oxidase activity. HVAP-1 is
      a 180 kDa homodimeric glycoprotein consisting of a membrane-spanning domain and
      three predicted extracellular copper-containing amine oxidase domains. In HVAP-1
      the extracellular domains are composed of a large domain D4, containing the
      active site and forming the interface of the dimer, while the smaller D2 and D3
      domains surround the D4 dimer near the entrance to the active site. The
      structural model of the catalytic D4 domain of HVAP-1 reveals that all components
      necessary for enzymatic monoamine oxidase activity are indeed present within the
      HVAP-1 and pinpoints residues that may be key to substrate entry through a
      channel to the active site and residues likely to be involved in substrate
      specificity as well as structural features critical to dimer formation. Proper
      glycosylation is required for the cell adhesion function of HVAP-1 and the
      predicted location of the sugar units at the solvent-exposed surface suits this
      function well.

PMID- 9930669
TI  - Random mutagenesis into the conserved Gly154 of subtilisin E: isolation and
      characterization of the revertant enzymes.
AB  - We analyzed the role played by the conserved Gly154, a constituent of the P1
      substrate-binding pocket of Bacillus subtilis subtilisin E, in the catalytic
      properties of the protease. Using an Escherichia coli expression system, the
      termination codon at position 154 in subtilisin E was first introduced to abolish
      the catalytic activity through truncation of the C-terminus from amino acid
      residues 154-275. We then attempted to obtain revertants with substitutions of
      various amino acids at position 154 by the polymerase chain reaction using a
      mixture of oligonucleotides. In addition to the Gly residue (wild-type), six
      amino acid substitutions (Ala, Arg, Leu, Phe, Pro and Thr) gave caseinolytic
      activity. When assayed with synthetic peptide substrates, most of the revertants
      showed a considerable decrease in specific activity and a P1 specificity similar
      to that of the wild-type enzyme. An Ala154 mutant purified from the periplasmic
      space in E. coli, however, resulted in an up to 2.3-fold preference for Val
      rather than Pro as a P2 substrate relative to the wild-type. Further, a
      significant 2-10-fold increase in the catalytic efficiency occurred in the
      Gly127Ala plus Gly154Ala combination variant, relative to the single Gly127Ala
      variant, without any change in the restricted specificity. The kinetic data and
      molecular modeling analysis demonstrate the important role of position 154 in the
      catalytic efficiency as well as in the substrate specificity of subtilisin E.

PMID- 9930670
TI  - Misfolding of chloramphenicol acetyltransferase due to carboxy-terminal
      truncation can be corrected by second-site mutations.
AB  - Folding of chloramphenicol acetyltransferase (CAT) in Escherichia coli is
      hampered by deletion of the carboxy-terminal tail including the last residue of
      the carboxy-terminal alpha-helix. Such truncated CAT polypeptides quantitatively
      aggregate into cytoplasmic inclusion bodies, which results in absence of a
      chloramphenicol-resistant phenotype for the producing host. In this paper, a
      genetic approach is presented to examine this aggregation process in more detail.
      Random mutagenesis of inactive CAT followed by direct phenotypic selection for
      revertants with restored chloramphenicol resistance was used to isolate second
      site suppressors of inactive truncation mutants of CAT. Two random mutagenesis
      procedures, independently of each other, yielded a unique substitution of Phe for
      Leu at amino acid position 145. This second-site mutation does not drastically
      affect the proteins' stability under normal growth conditions of E. coli. Hence,
      the introduction of Phe at amino acid position 145 improves the ability of the
      protein to fold into a soluble, enzymatically active conformation. The
      conservative character of the Leu145Phe replacement indicates that limited
      changes at crucial positions can have important effects on protein folding in
      vivo.

PMID- 9930672
TI  - Engineered human carboxypeptidase B enzymes that hydrolyse hippuryl-L-glutamic
      acid: reversed-polarity mutants.
AB  - Variants of human pancreatic carboxypeptidase B (HCPB), with specificity for
      hydrolysis of C-terminal glutamic acid and aspartic acid, were prepared by site
      directed mutagenesis of the human gene and expressed in the periplasm of
      Escherichia coli. By changing residues in the lining of the S1' pocket of the
      enzyme, it was possible to reverse the substrate specificity to give variants
      able to hydrolyse prior to C-terminal acidic amino acid residues instead of the
      normal C-terminal basic residues. This was achieved by mutating Asp253 at the
      base of the S1' specificity pocket, which normally interacts with the basic side
      chain of the substrate, to either Lys or Arg. The resulting enzymes had the
      desired reversed polarity and enzyme activity was improved significantly with
      further mutations at residue 251. The [G251T,D253K]HCPB double mutant was 100
      times more active against hippuryl-L-glutamic acid (hipp-Glu) as substrate than
      was the single mutant, [D253K]HCPB. Triple mutants, containing additional changes
      at Ala248, had improved activity against hipp-Glu substrate when position 251 was
      Asn. These reversed-polarity mutants of a human enzyme have the potential to be
      used in antibody-directed enzyme prodrug therapy of cancer.

PMID- 9930671
TI  - Thermostable glycerol kinase from a hyperthermophilic archaeon: gene cloning and
      characterization of the recombinant enzyme.
AB  - The Pk-glpK gene, which encodes glycerol kinase (GK) from a hyperthermophilic
      archaeon Pyrococcus kodakaraensis KOD1, was cloned and expressed in Escherichia
      coli. The amino acid sequence of this enzyme (Pk-GK) deduced from the nucleotide
      sequence showed 57% identity with that of E. coli GK and 47% identity with that
      of human GK. Pk-GK, which has a molecular weight of 55902 (497 amino acid
      residues), was purified from E. coli and characterized. Despite the high sequence
      similarity, Pk-GK and E. coli GK are greatly divergent in structure and function
      from each other. Unlike E. coli GK, which exists as a tetramer, Pk-GK exists as a
      dimer. The preferred divalent cation for Pk-GK is Co2+, instead of Mg2+. The
      optimum pH and temperature for Pk-GK activity are 8.0 and 80 degrees C,
      respectively. Pk-GK can utilize other nucleoside triphosphates than ATP as a
      phosphoryl donor. It is fairly resistant to an allosteric inhibitor of E. coli
      GK, fructose-1,6-bisphosphate. Determination of the kinetic parameters indicates
      that the Km value of the enzyme is 15.4 microM for ATP and 111 microM for
      glycerol and its kcat value is 940 s(-1). The enzyme was shown to be fairly
      resistant to irreversible heat inactivation and still retained 50% of its
      enzymatic activity even after heating at 100 degrees C for 30 min. Construction
      of a model for the three-dimensional structure of the enzyme suggests that the
      formation of extensive ion-pair networks is responsible for the high stability of
      this enzyme.

PMID- 9930673
TI  - Molecular modelling and site-directed mutagenesis of the active site of
      endothelin-converting enzyme.
AB  - Mammalian endothelin-converting enzyme is a membrane-bound metalloprotease; its C
      terminal domain contains sequence motifs characteristic of zinc metalloproteases.
      We examined residues expected from molecular modelling to be important for
      substrate binding using selectively mutated recombinant rat ECE-1alpha expressed
      in CHO cells. A conserved N-A-Ar-Ar (Ar = aromatic) motif is likely to be
      important for substrate binding. Mutating N550 to Gln or Y552 to Phe reduces
      Vmax/Km by 8- and 18-fold, respectively. The equivalent residue to Y553 in
      thermolysin binds the inhibitor through its NH group. Removing this putative
      interaction by mutating Tyr to Pro destroys activity, but mutating it to Ala or
      Phe also removes most activity. Mutating G583 (in a conserved GGI motif N
      terminal of the zinc-binding helix) to Ala has no measurable effect, but mutating
      G584 to Ala destroys activity. Changing V583 in the zinc-binding helix to Met, to
      mimic the sequence pattern in bovine ECE-2, increases Vmax/Km to 1.7-fold that of
      the wild-type. Assays of phosphoramidon binding follow the pattern of those of
      substrate binding, but the IC50 of the more potent ECE inhibitor CGS 26303 was
      not significantly altered by any of these mutations, suggesting that this
      compound may bind to ECE in a different mode from phosphoramidon.

PMID- 9930674
TI  - Protein engineering of chimeric Serpins: an investigation into effects of the
      serpin scaffold and reactive centre loop length.
AB  - The exposed Serpin reactive centre loop controls the specificity of the serpin
      proteinase interaction. Mutations within this region have been used to generate
      novel potentially therapeutic inhibitors. In this study we examine the effect of
      the serpin scaffold and reactive centre loop length upon the generation of such
      inhibitors. The reactive centre loop regions, P7-P3', of alpha1-antitrypsin and
      alpha1-antichymotrypsin were replaced by the corresponding residues of the viral
      serpin, Serp1, to form AT/Serp1 and ACT/Serp1, respectively. AT/Serp1 formed SDS
      stable complexes with a range of proteinases with association rate constants for
      plasmin, tissue plasminogen activator, urokinase, thrombin and factor Xa of
      approximately 10(4) M(-1)s(-1) and a stoichiometry of inhibition of approximately
      1 for all of them. ACT/Serp1, however, formed SDS-stable complexes with only
      plasmin and thrombin with association rate constant 100-fold slower than AT/Serp1
      and an increased stoichiometry of inhibition. The reactive centre loop of
      ACT/Serp1 is four amino acid residues longer than AT/Serp1. These four additional
      residues (VETR) were inserted into AT/Serp1 to form AT/Serp1(VETR).
      AT/Serp1(VETR) formed SDS stable complexes with plasmin, thrombin and tissue
      plasminogen activator similar to AT/Serp1, however, the association rate
      constants were 10-fold slower than those observed with AT/Serp1, while the
      stoichiometry of inhibition remained around 1. These results suggest that the
      additional reactive centre loop residues effect the rate of initial complex
      formation by placing the reactive centre loop in a non-ideal conformation. This
      study demonstrates that both reactive centre loop length and serpin scaffold are
      important in defining the inhibitory characteristics of a serpin.

PMID- 9930675
TI  - Expression of apolipoprotein(a) kringle IV type 9 in Escherichia coli:
      demonstration of a specific interaction between kringle IV type 9 and
      apolipoproteinB-100.
AB  - A number of studies have provided evidence that lipoprotein(a) [Lp(a)] assembly
      is a two-step process in which initial non-covalent interactions between
      apolipoprotein(a) [apo(a)] and apolipoproteinB-100 (apoB-100) precede specific
      disulfide bond formation. We have designed a construct encoding apo(a) kringle IV
      type 9 (KIV9) in which the unpaired cysteine at position 67 in this kringle is
      replaced with a tyrosine. The single kringle was expressed in bacteria and
      purified to homogeneity from cell homogenates. The purified derivative
      (designated KIV9deltaCys) was assessed for its ability to bind to purified human
      LDL. This interaction was detected either by ELISA using immobilized LDL or by
      column chromatography in which LDL binding to KIV9deltaCys immobilized on Ni2+
      Sepharose was determined. In both cases, the interaction of KIV9deltaCys and LDL
      was observed. Further, we demonstrated that the binding interaction was sensitive
      to the addition of amino acids including lysine, the lysine analogue epsilon
      aminocaproic acid, arginine, phenylalanine and proline, with arginine and lysine
      having the greatest inhibitory effect. Binding of KIV9deltaCys to an immobilized
      apoB peptide spanning residues 3732-3745 of apoB was also demonstrated by ELISA.
      As was the case for LDL, this binding interaction was sensitive to the addition
      of arginine and lysine. Computer modeling of KIV9 demonstrated an excellent fit
      with residues 3732-3738 (PSCKLDF) of the apoB peptide. The modeling predicts the
      presence of overlapping lysine and phenylalanine-binding pockets in KIV9 which
      explains the inhibitory effects of lysine, arginine and phenylalanine which were
      observed in the binding assays. In summary, this study represents the first
      demonstration that KIV9 can interact directly with LDL through non-covalent
      interactions which may contribute to the first step of Lp(a) formation.

PMID- 9930676
TI  - Engineering, characterization and phage display of hepatitis C virus NS3 protease
      and NS4A cofactor peptide as a single-chain protein.
AB  - The polyprotein encoded by hepatitis C virus (HCV) genomic RNA is processed into
      functional polypeptides by both host- and virus-encoded proteases. The HCV
      encoded NS3 protease and its cofactor peptide NS4A form a non-covalent complex,
      which participates in processing the viral polyprotein. This proteolytic activity
      is believed to be essential for virus proliferation and thus the NS3 protease is
      a prime target for developing anti-HCV pharmacological agents. Recent X-ray
      crystallography structural studies have revealed the nature of this non-covalent
      complex between NS3 protease and the 'active' central segment of NS4A, providing
      the opportunity to design a single-chain polypeptide. To this end, the DNA
      sequence encoding for the NS4A peptide (residues 21-34) was genetically fused via
      a short linker, capable of making a beta-turn, to the N-terminus of the NS3
      protease domain. This engineered single-chain NS3-protease (scNS3) is fully
      active with kinetic parameters virtually identical with those of the NS3/ NS4A
      non-covalent complex. Moreover, the scNS3 protease can be displayed on
      filamentous phage and affinity selected using an immobilized specific inhibitor.
      The scNS3 expressed as a soluble protein and in a phage-display format
      facilitates enzyme engineering for further structural studies and in vitro
      selection of potential drug-resistant mutants. These are important steps towards
      developing effective anti-protease compounds.

PMID- 9930677
TI  - Absolute conservation of residue 6 of immunoglobulin heavy chain variable regions
      of class IIA is required for correct folding.
AB  - While studying the expression of single-chain antibodies (scFv) derived from
      several murine monoclonal antibodies, we found that residue 6 in Framework region
      1 of the heavy chain variable domain plays a crucial role in antibody folding.
      Binding activity of three murine antibodies with a heavy chain variable region
      (VH) subgroup IIA was completely lost when at this position the wild-type residue
      glutamine (Q) was substituted by glutamate (E). Increased sensitivity towards
      trypsin digestion of soluble scFv suggested that the lack of binding activity was
      caused by incorrect folding of Q6E mutants. Grafting of the three additional
      class IA derived FR1 residues, based upon the comparison between both classes of
      VH sequences, on to the 'defect' subgroup IIA sequence, partially restored the
      antigen binding activity of the Q6E-containing scFv. Our results suggest that
      residue 6 of the heavy chain may be part of a folding nucleus, involving the
      first two beta-strands of Framework region 1. The evolutionary conservation of
      either glutamine or glutamate at position 6 in different antibody families may
      well indicate that within immunoglobulin VH domains, different family specific
      folding nuclei have evolved.

PMID- 9930678
TI  - Single-chain Fv with manifold N-glycans as bifunctional scaffolds for
      immunomolecules.
AB  - Unlike natural antibodies, single-chain Fv (sFv) proteins normally lack
      asparagine-linked glycosylation. Many designed immunoconjugates and other
      therapeutics currently employ the advantageous conjugation chemistry or targeting
      properties provided by the glycoprotein oligosaccharide domain. sFv proteins with
      engineered N-glycan designs were evaluated in Pichia pastoris for glycosylation
      efficiency, expression level, oligosaccharide chain length and composition, and
      affinity. In contrast to nearly all natural glycoproteins, the engineered
      attachment of N-glycans conveniently near the polypeptide C-terminus was found to
      produce the optimal results. Furthermore, the percentage modification and chain
      length of the attached mannose chains were controllable by the use of tandem and
      overlapping Asn-X-Thr tripeptide sites. The glycosylated sFv mannose chains could
      be effectively conjugated to polyethylene glycol and the resulting conjugate
      displayed a 10-fold increased circulating life in mice. The potential to control
      polymer:sFv or drug:sFv molar ratios by site-specific conjugation may
      substantially improve the therapeutic efficacy of these minimal antigen-binding
      molecules.

PMID- 9930679
TI  - Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human
      'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas.
AB  - The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a
      gene encoding human epidermal growth factor (hEGF). The hybrid human protein was
      isolated from Escherichia coli inclusion bodies, refolded and purified to
      homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF
      receptors (EGFR) and had ribonucleolytic activities approaching those of
      hpRNase1. Several conformations having different enzymatic activities could be
      detected after reversed-phase high-performance liquid chromatographic analysis,
      the less hydrophobic molecules being the most active. The hybrid protein was
      specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell
      line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1
      had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was
      not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR
      deficient control cells. Taken together, these data suggest that this construct
      might be useful for targeted therapy of esophageal, lung and other squamous cell
      carcinomas and also breast cancers overexpressing EGFR, which correlate with a
      poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules
      with endogenous human proteins for targeted therapy may alleviate the dose
      limiting immunogenicity and toxicity of conventional immunotoxins.

PMID- 9930680
TI  - Chaperonin GroE-facilitated refolding of disulfide-bonded and reduced Taka
      amylase A from Aspergillus oryzae.
AB  - The refolding characteristics of Taka-amylase A (TAA) from Aspergillus oryzae in
      the presence of the chaperonin GroE were studied in terms of activity and
      fluorescence. Disulfide-bonded (intact) TAA and non-disulfide-bonded (reduced)
      TAA were unfolded in guanidine hydrochloride and refolded by dilution into buffer
      containing GroE. The intermediates of both intact and reduced enzymes were
      trapped by GroEL in the absence of nucleotide. Upon addition of nucleotides such
      as ATP, ADP, CTP or UTP, the intermediates were released from GroEL and recovery
      of activity was detected. In both cases, the refolding yields in the presence of
      GroEL and ATP were higher than spontaneous recoveries. Fluorescence studies of
      intrinsic tryptophan and a hydrophobic probe, 8-anilinonaphthalene-1-sulfonate,
      suggested that the intermediates trapped by GroEL assumed conformations with
      different hydrophobic properties. The presence of protein disulfide isomerase or
      reduced and oxidized forms of glutathione in addition to GroE greatly enhanced
      the refolding reaction of reduced TAA. These findings suggest that GroE has an
      ability to recognize folding intermediates of TAA protein and facilitate
      refolding, regardless of the existence or absence of disulfide bonds in the
      protein.

PMID- 9930681
TI  - Embryonic stem-cell research exempt from ban, NIH is told.

PMID- 9930682
TI  - Insider trading alert over bioscience companies.

PMID- 9930683
TI  - Biochemistry panel dropped from UK quality review.

PMID- 9930684
TI  - Tough times set to continue for US biotech start-ups.

PMID- 9930685
TI  - The writing is on the web for science journals in print.

PMID- 9930686
TI  - Close the South-North knowledge gap.

PMID- 9930687
TI  - Luddites must not block progress in genetics.

PMID- 9930688
TI  - Computers and the copyright conundrum.

PMID- 9930689
TI  - Who pays what in drug development.

PMID- 9930690
TI  - Molecular motors join forces.

PMID- 9930691
TI  - Translational control perks up.

PMID- 9930692
TI  - Telomeres. Capping off the ends.

PMID- 9930693
TI  - Hydrogenase sophistication.

PMID- 9930694
TI  - Neurobiology. A homeostatic switch.

PMID- 9930695
TI  - Fas-mediated cell death promoted by opioids.

PMID- 9930696
TI  - Shikimate pathway in apicomplexan parasites.

PMID- 9930697
TI  - The generation of martian floods by the melting of ground ice above dykes.
AB  - The surface of Mars is cut by long linear faults with displacements of metres to
      kilometres, most of which are thought to have been formed by extension. The
      surface has also been modified by enormous floods, probably of water, which often
      flowed out of valleys formed by the largest of these faults. By analogy with
      structures on Earth, we propose here that the faults are in fact the surface
      expression of dykes, and not of large-scale tectonic movements. We use a
      numerical model to show that the intrusion of large dykes can generate structures
      like Valles Marineris. Such dykes can provide a heat source to melt ground ice,
      and so provide a source of water for the floods that have been inferred to
      originate in some of the large valleys.

PMID- 9930698
TI  - Nanometre-scale rolling and sliding of carbon nanotubes.
AB  - Understanding the relative motion of objects in contact is essential for
      controlling macroscopic lubrication and adhesion, for comprehending biological
      macromolecular interfaces, and for developing submicrometre-scale
      electromechanical devices. An object undergoing lateral motion while in contact
      with a second object can either roll or slide. The resulting energy loss and
      mechanical wear depend largely on which mode of motion occurs. At the macroscopic
      scale, rolling is preferred over sliding, and it is expected to have an equally
      important role in the microscopic domain. Although progress has been made in our
      understanding of the dynamics of sliding at the atomic level, we have no
      comparable insight into rolling owing to a lack of experimental data on
      microscopic length scales. Here we produce controlled rolling of carbon nanotubes
      on graphite surfaces using an atomic force microscope. We measure the
      accompanying energy loss and compare this with sliding. Moreover, by reproducibly
      rolling a nanotube to expose different faces to the substrate and to an external
      probe, we are able to study the object over its complete surface.

PMID- 9930699
TI  - The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal
      maturation.
AB  - GABA (gamma-aminobutyric acid) is the main inhibitory transmitter in the adult
      brain, and it exerts its fast hyperpolarizing effect through activation of anion
      (predominantly Cl-)-permeant GABA(A) receptors. However, during early neuronal
      development, GABA(A)-receptor-mediated responses are often depolarizing, which
      may be a key factor in the control of several Ca2+-dependent developmental
      phenomena, including neuronal proliferation, migration and targeting. To date,
      however, the molecular mechanism underlying this shift in neuronal
      electrophysiological phenotype is unknown. Here we show that, in pyramidal
      neurons of the rat hippocampus, the ontogenetic change in GABA(A)-mediated
      responses from depolarizing to hyperpolarizing is coupled to a developmental
      induction of the expression of the neuronal (Cl-)-extruding K+/Cl- co
      transporter, KCC2. Antisense oligonucleotide inhibition of KCC2 expression
      produces a marked positive shift in the reversal potential of GABAA responses in
      functionally mature hippocampal pyramidal neurons. These data support the
      conclusion that KCC2 is the main Cl- extruder to promote fast hyperpolarizing
      postsynaptic inhibition in the brain.

PMID- 9930700
TI  - Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP
      and TRPL.
AB  - Phototransduction in invertebrate microvillar photoreceptors is thought to be
      mediated by the activation of phospholipase C (PLC), but how this leads to gating
      of the light-sensitive channels is unknown. Most attention has focused on
      inositol-1,4,5-trisphosphate, a second messenger produced by PLC from
      phosphatidylinositol-4,5-bisphosphate; however, PLC also generates
      diacylglycerol, a potential precursor for several polyunsaturated fatty acids,
      such as arachidonic acid and linolenic acid. Here we show that both of these
      fatty acids reversibly activate native light-sensitive channels (transient
      receptor potential (TRP) and TRP-like (TRPL)) in Drosophila photoreceptors as
      well as recombinant TRPL channels expressed in Drosophila S2 cells. Recombinant
      channels are activated rapidly in both whole-cell recordings and inside-out
      patches, with a half-maximal effector concentration for linolenic acid of
      approximately 10 microM. Four different lipoxygenase inhibitors, which might be
      expected to lead to build-up of endogenous fatty acids, also activate native TRP
      and TRPL channels in intact photoreceptors. As arachidonic acid may not be found
      in Drosophila, we suggest that another polyunsaturated fatty acid, such as
      linolenic acid, may be a messenger of excitation in Drosophila photoreceptors.

PMID- 9930701
TI  - Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol.
AB  - Eukaryotic cells respond to many hormones and neurotransmitters with increased
      activity of the enzyme phospholipase C and a subsequent rise in the concentration
      of intracellular free calcium ([Ca2+]i). The increase in [Ca2+]i occurs as a
      result of the release of Ca2+ from intracellular stores and an influx of Ca2+
      through the plasma membrane; this influx of Ca2+ may or may not be store
      dependent. Drosophila transient receptor potential (TRP) proteins and some
      mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+
      entry. Here we describe the molecular mechanism of store-depletion-independent
      activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a
      non-selective cation channel that is activated by diacylglycerol in a membrane
      delimited fashion, independently of protein kinases C activated by
      diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is
      activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1
      are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the
      first members of a new functional family of second-messenger-operated cation
      channels, which are activated by diacylglycerol.

PMID- 9930702
TI  - ICOS is an inducible T-cell co-stimulator structurally and functionally related
      to CD28.
AB  - The T-cell-specific cell-surface receptors CD28 and CTLA-4 are important
      regulators of the immune system. CD28 potently enhances those T-cell functions
      that are essential for an effective antigen-specific immune response, and the
      homologous CTLA-4 counterbalances the CD28-mediated signals and thus prevents an
      otherwise fatal overstimulation of the lymphoid system. Here we report the
      identification of a third member of this family of molecules, inducible co
      stimulator (ICOS), which is a homodimeric protein of relative molecular mass
      55,000-60,000 (M(r) 55K-60K). Matching CD28 in potency, ICOS enhances all basic T
      cell responses to a foreign antigen, namely proliferation, secretion of
      lymphokines, upregulation of molecules that mediate cell-cell interaction, and
      effective help for antibody secretion by B cells. Unlike the constitutively
      expressed CD28, ICOS has to be de novo induced on the T-cell surface, does not
      upregulate the production of interleukin-2, but superinduces the synthesis of
      interleukin-10, a B-cell-differentiation factor. In vivo, ICOS is highly
      expressed on tonsillar T cells, which are closely associated with B cells in the
      apical light zone of germinal centres, the site of terminal B-cell maturation.
      Our results indicate that ICOS is another major regulator of the adaptive immune
      system.

PMID- 9930703
TI  - Direct interaction of microtubule- and actin-based transport motors.
AB  - The microtubule network is thought to be used for long-range transport of
      cellular components in animal cells whereas the actin network is proposed to be
      used for short-range transport, although the mechanism(s) by which this transport
      is coordinated is poorly understood. For example, in sea urchins long-range Ca2+
      regulated transport of exocytotic vesicles requires a microtubule-based motor,
      whereas an actin-based motor is used for short-range transport. In neurons,
      microtubule-based kinesin motor proteins are used for long-range vesicular
      transport but microtubules do not extend into the neuronal termini, where actin
      filaments form the cytoskeletal framework, and kinesins are rapidly degraded upon
      their arrival in neuronal termini, indicating that vesicles may have to be
      transferred from microtubules to actin tracks to reach their final destination.
      Here we show that an actin-based vesicle-transport motor, MyoVA, can interact
      directly with a microtubule-based transport motor, KhcU. As would be expected if
      these complexes were functional, they also contain kinesin light chains and the
      localization of MyoVA and KhcU overlaps in the cell. These results indicate that
      cellular transport is, in part, coordinated through the direct interaction of
      different motor molecules.

PMID- 9930704
TI  - Protein translation and folding are coupled by an endoplasmic-reticulum-resident
      kinase.
AB  - Protein synthesis and the folding of the newly synthesized proteins into the
      correct three-dimensional structure are coupled in cellular compartments of the
      exocytosis pathway by a process that modulates the phosphorylation level of
      eukaryotic initiation factor-2alpha (eIF2alpha) in response to a stress signal
      from the endoplasmic reticulum (ER). Activation of this process leads to reduced
      rates of initiation of protein translation during ER stress. Here we describe the
      cloning of perk, a gene encoding a type I transmembrane ER-resident protein. PERK
      has a lumenal domain that is similar to the ER-stress-sensing lumenal domain of
      the ER-resident kinase Ire1, and a cytoplasmic portion that contains a protein
      kinase domain most similar to that of the known eIF2alpha kinases, PKR and HRI.
      ER stress increases PERK's protein-kinase activity and PERK phosphorylates
      eIF2alpha on serine residue 51, inhibiting translation of messenger RNA into
      protein. These properties implicate PERK in a signalling pathway that attenuates
      protein translation in response to ER stress.

PMID- 9930705
TI  - Transmyocardial laser revascularization: effect of laser parameters on tissue
      ablation and cardiac perfusion.
AB  - Dr. Mahmood Mirhoseini from Milwaukee, WI, transformed transmyocardial
      revascularization (TMR) into transmyocardial laser revascularization (TMLR) more
      than 2 decades ago. The controversial nature of this laser procedure and the
      prospect of its successful application to refractory cases of chronic
      debilitating angina have created spirited interest in TMLR. As a natural
      component of this interest, various laser modalities have been proposed and
      employed during the performance of the TMLR procedure both in the experimental
      and the clinical setting. However, it is the nature of laser-tissue interactions
      that is primarily responsible for the long-term fate of the channels, the
      angiogenesis that occurs in the vicinity of these laser channels, and the
      resulting increase (if any) in myocardial perfusion. These interactions with
      tissue are, in turn, determined by laser variables such as photonic absorption
      and scattering by the target tissue, pulse energy and duration, and the peak
      power generated. The CO2 laser has the advantages of producing high-energy pulses
      that create a transmural channel with a single pulse, low-peak power that
      minimizes structural tissue trauma, and high photonic absorption to minimize
      thermal damage. The holmium:YAG and excimer lasers, in turn, have the advantage
      of being coupled to a fiber optic catheter for transluminal endocardial delivery.
      Importantly, long-term clinical and perfusional data showing a cause and effect
      relationship between the use of TMLR and these end-points are available for the
      CO2 laser only. Prospective randomized trials are, therefore, warranted to
      delineate the use of each laser modality in relation to that of the CO2 laser in
      the TMLR setting.

PMID- 9930706
TI  - Transmyocardial laser revascularization with the CO2 laser: one year results of a
      randomized, controlled trial.
AB  - Transmyocardial laser revascularization (TMR) was compared to continued medical
      management in 198 patients with symptomatic end-stage coronary artery disease in
      a 1:1 randomized prospective study. Angina class, quality of life, and myocardial
      perfusion significantly improved following TMR over a 12-month period of follow
      up. Continued medical management was associated with a higher incidence of
      unstable anginal episodes, repeat hospitalizations, worsening anginal class and
      myocardial perfusion. This study demonstrates the superiority of TMR over medical
      management in the treatment of chronic stable angina. With appropriate patient
      selection and perioperative management, TMR with the CO2 laser is associated with
      a very low operative risk.

PMID- 9930707
TI  - Clinical experience with the holmium:YAG laser for transmyocardial laser
      revascularization and myocardial denervation as a mechanism.
AB  - Transmyocardial laser revascularization is emerging as a treatment option for
      patients with debilitating angina pectoris and no conventional treatment option.
      Results with the high powered CO2 laser have been reproducibly encouraging. As
      the mechanism of action remains uncertain, the importance of the type of laser
      used is unknown. Interest in developing less invasive approaches, ultimately
      including catheter-based technologies, has stimulated the evaluation of
      alternative laser energy sources with fiberoptic delivery systems. One such
      device is the holmium:YAG laser. Clinical experience with the holmium:YAG-based
      systems is still in its early stages. We review our experience with one such
      device and the existing literature on the subject. We also briefly describe
      experimental evidence that this device is capable of denervating the heart
      locally.

PMID- 9930708
TI  - An examination of potential mechanisms underlying transmyocardial laser
      revascularization induced increases in myocardial blood flow.
AB  - Within the past few years, transmyocardial laser revascularization (TMR) has
      attracted the attention of cardiologists and cardiac surgeons as a therapy for
      patients suffering from otherwise treatable coronary artery disease. Clinical
      studies have consistently shown symptomatic improvement that lasts at least 1
      year in a majority of patients. The original hypothesis that prompted development
      of the technique was that direct myocardial perfusion from the chamber could be
      achieved through chronically patent channels, as is the case in reptilian hearts.
      Results of our early studies failed to support this hypothesis and we turned to
      investigations aimed at testing other possible explanations. The experiments,
      which are reviewed in this article, showed that TMR enhances vascular growth in
      ischemic myocardium.

PMID- 9930709
TI  - Transmyocardial laser revascularization and angiogenesis: the potential for
      therapeutic benefit.
AB  - Transmyocardial laser revascularization (TMR) has emerged as a promising therapy
      for ischemic heart disease in patients who are not candidates for more
      conventional therapies such as percutaneous transluminal coronary angioplasty or
      coronary artery bypass grafting. Although TMR provides symptomatic relief of
      angina and improved cardiovascular performance in a select patient population,
      the mechanism by which TMR works is still a controversial issue. Recently, it has
      been postulated that TMR evokes an angiogenic response and thereby improves local
      perfusion to ischemic myocardial territories. Herein we present a review of TMR
      and the molecular basis of angiogenesis.

PMID- 9930710
TI  - Combination TMR and gene therapy.
AB  - Transmyocardial laser revascularization is a promising surgical technique that
      relieves angina and improves subendocardial perfusion in patients with chronic
      ischemic heart disease refractory to medical management and not amenable to
      conventional revascularization techniques. We detail our laboratory experience at
      the Brigham and Women's Hospital with transmyocardial laser revascularization and
      discuss the potential clinical applications of this work.

PMID- 9930711
TI  - Myasthenia gravis: clinical features, pathogenesis, evaluation, and medical
      management.
AB  - Myasthenia gravis is a disorder characterized by weakness and fatigue of
      voluntary muscles. The muscular disorder is generalized in 85% and confined to
      extraocular muscles in 15% of patients. The disease is graded based on pattern
      and severity of muscular involvement. Myasthenia gravis is an autoimmune disease
      which leads to a reduction of the number of acetylcholine receptors (Ach-R) at
      the muscular motor endplate. This results in less receptors available for
      stimulation, lower amplitude stimulations, less muscle fiber activation, and the
      resultant clinical findings of weakness in the affected muscles. The work-up and
      treatment of this disease originated from an understanding of its pathogenesis.
      Diagnostic tests include use of anticholinesterase agents (tensilon test), curare
      test, repetitive nerve stimulation, Ach-R antibody assay, and single fiber
      electromyography. Medical therapy includes use of anticholinesterase agents,
      immunotherapy, and plasmapheresis.

PMID- 9930712
TI  - Preoperative preparation and anesthetic management of patients with myasthenia
      gravis.
AB  - Patients with myasthenia gravis have specific clinical problems that must be
      addressed by the anesthesiologist when surgery is contemplated. Optimal
      perioperative management of myasthenia gravis patients undergoing thymectomy
      requires careful preoperative assessment and preparation. This assessment and
      preparation includes evaluation for concomitant autoimmune, respiratory, and
      cardiac disorders as well as optimization of medical management for myasthenia.
      There are important intraoperative concerns to be addressed including appropriate
      monitoring, premedication, and other agents used during surgery including muscle
      relaxants and anesthetic agents. Postoperatively, attention must be directed
      specifically to pain relief, ventilatory management, and the appropriate
      titration of reversal agents and anticholinesterase inhibitors. Optimal
      management of all these factors maximizes the chance for successful and
      uncomplicated hospitalization.

PMID- 9930713
TI  - Transsternal thymectomy for myasthenia gravis.
AB  - A consistent, planned approach to thymectomy for patients with myasthenia gravis
      has been used at the University of North Carolina since 1977. This involves a
      sternotomy, with excision of the entire thymus and adjacent fatty tissues from
      the thyroid to the diaphragm and laterally to 1 cm from each phrenic nerve.
      Between 1977 and 1993, 100 consecutive patients were treated in this manner with
      no mortality. Eight-four percent of patients were extubated in the operating room
      or within 1 hour of surgery, and no patients experienced postoperative
      respiratory difficulty. After a mean follow-up of 65 months, 78% of all patients
      improved by at least one modified Osserman classification, and 69% of patients
      with preoperative class I, II, or III disease (maximal preoperative severity) are
      in pharmacological remission. We conclude that transsternal thymectomy is
      associated with minimal morbidity and no mortality, and results in long-term
      improvement in symptoms for patients with myasthenia gravis.

PMID- 9930714
TI  - Transcervical thymectomy.
AB  - Transcervical thymectomy is appropriate for managing carefully selected patients
      with myasthenia gravis due to its noninvasive nature, good cosmetic results, and
      favorable long-term outcomes. Contraindications to its use include the presence
      of a thymoma and advanced age. In optimally prepared patients, the operative
      complication rate is negligible and the average length of hospital stay is 1 to 2
      days. The ultimate results of therapy often are not evident for several years
      postoperatively, indicating that comprehensive preoperative and postoperative
      treatment by a qualified neurologist is essential in optimizing outcomes. A meta
      analysis of long-term results shows that 90% of patients who undergo the
      operation are improved, 80% become asymptomatic, and 50% achieve a complete
      remission.

PMID- 9930715
TI  - Video-assisted thoracoscopic thymectomy for myasthenia gravis.
AB  - Thymectomy is an established therapy in the management of generalized myasthenia
      gravis, in addition to medical treatment. However, the optimal surgical approach
      to thymectomy has remained controversial. There are advocates for transternal,
      transcervical approaches or "maximal" thymectomy. Video-assisted thoracic surgery
      (VATS) presents a new approach to thymectomy and forms the basis of this article,
      in which we discuss patient selection, technique, and results. We believe
      complete thymectomy, comparable with the transternal approach, could be achieved
      by VATS. Our intermediate-term results compare well with other surgical
      techniques. By minimizing chest wall trauma, VATS not only causes less
      postoperative pain, shortens hospital stay, gives better cosmetic results but
      also leads to wider acceptance by patients (and their neurologists) for earlier
      surgery. However, the true role of this approach in thoracic surgery awaits long
      term results.

PMID- 9930716
TI  - Regulation of amyloid precursor protein cleavage.
AB  - Multiple lines of evidence suggest that increased production and/or deposition of
      the beta-amyloid peptide, derived from the amyloid precursor protein, contributes
      to Alzheimer's disease. A growing list of neurotransmitters, growth factors,
      cytokines, and hormones have been shown to regulate amyloid precursor protein
      processing. Although traditionally thought to be mediated by activation of
      protein kinase C, recent data have implicated other signaling mechanisms in the
      regulation of this process. Moreover, novel mechanisms of regulation involving
      cholesterol-, apolipoprotein E-, and stress-activated pathways have been
      identified. As the phenotypic changes associated with Alzheimer's disease
      encompass many of these signaling systems, it is relevant to determine how
      altered cell signaling may be contributing to increasing brain amyloid burden. We
      review the myriad ways in which first messengers regulate amyloid precursor
      protein catabolism as well as the signal transduction cascades that give rise to
      these effects.

PMID- 9930717
TI  - Molecular cloning of a putative cyclic nucleotide-gated ion channel cDNA from
      Limulus polyphemus.
AB  - Cyclic nucleotide-gated channels have been proposed to mediate the electrical
      response to light in the ventral photoreceptor cells of the horseshoe crab,
      Limulus polyphemus. However, a cyclic nucleotide-gated channel has not been
      identified from Limulus. We have cloned a putative full-length cyclic nucleotide
      gated channel cDNA by screening cDNA libraries constructed from Limulus brain
      using a probe developed from Limulus ventral eye nerves. The putative full-length
      cDNA was derived from two overlapping partial cDNA clones. The open reading frame
      encodes 905 amino acids; the sequence shows 44% identity to that of the alpha
      subunit of the bovine rod cyclic GMP-gated channel over the region containing the
      transmembrane domains and the cyclic nucleotide binding domain. This Limulus
      channel has a novel C-terminal region of approximately 200 amino acids,
      containing three putative Src homology domain 3 binding motifs and a putative
      coiled-coil domain. The possibility that this cloned channel is the same as that
      detected previously in excised patches from the photoreceptive membrane of
      Limulus ventral photoreceptors is discussed in terms of its sequence and its
      expression in the ventral eye nerves.

PMID- 9930718
TI  - Cytokine induction of inducible nitric oxide synthase in an oligodendrocyte cell
      line: role of p38 mitogen-activated protein kinase activation.
AB  - The induction of inducible nitric oxide synthase (iNOS) by proinflammatory
      cytokines was studied in an oligodendrocyte progenitor cell line in relation to
      mitogen-activated protein kinase (MAPK) activation and cytokine-mediated
      cytotoxicity. When introduced individually to cultures of CG4 cells, the
      cytokines, i.e., tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1),
      and interferon-gamma (IFN gamma), had either minimal (TNF alpha) or no (IL-1 and
      IFN gamma) detectable stimulatory effect on the production of nitric oxide.
      However, combinations of these factors, in particular, TNF alpha plus IFN gamma,
      elicited a strong enhancement of nitric oxide synthesis and, as revealed by
      western blot and RT-PCR analysis, the expression of iNOS. TNF alpha and IL-1 were
      able to activate p38 MAPK in a time- and dose-dependent manner and together
      showed a combinatorial effect. In contrast, IFN gamma neither activated on its
      own nor enhanced the activation of p38 MAPK in response to TNF alpha and IL-1.
      However, a specific inhibitor of p38 MAPK, i.e., SB203580, inhibited the
      induction of iNOS in cytokine combination-treated cells in a dose-dependent
      manner, thereby suggesting a role for the MAPK cascade in regulating the
      induction of iNOS gene expression in cytokine-treated cells. Blocking of nitric
      oxide production by an inhibitor of iNOS, i.e., nitro-L-arginine methyl ester,
      had a minimal protective effect against cytokine-mediated cytotoxicity that
      occurred before the elevation of nitric oxide levels, thereby indicating temporal
      and functional dissociation of nitric oxide production from cell killing.

PMID- 9930720
TI  - Serine-23 is a major protein kinase A phosphorylation site on the amino-terminal
      head domain of the middle molecular mass subunit of neurofilament proteins.
AB  - We have shown previously that phosphate groups on the amino-terminal head domain
      region of the middle molecular mass subunit of neurofilament proteins (NF-M) are
      added by second messenger-dependent protein kinases. Here, we have identified
      Ser23 as a specific protein kinase A phosphorylation site on the native NF-M
      subunit and on two synthetic peptides, S1 (14RRVPTETRSSF24) and S2
      (21RSSFSRVSGSPSSGFRSQSWS41), localized within the amino-terminal head domain
      region. Ser23 was identified as a phosphorylation site on the 32P-labeled alpha
      chymotryptic peptide that carried >80% of the 32P-phosphates incorporated into
      the NF-M subunit by protein kinase A. The synthetic peptides S1 and S2 were
      phosphorylated 18 and two times more efficiently by protein kinase A than protein
      kinase C, respectively. Neither of the peptides was phosphorylated by casein
      kinase II. The sequence analyses of the chemically modified phosphorylated serine
      residues showed that Ser23 was the major site of phosphorylation for protein
      kinase A on both S1 and S2 peptides. Low levels of incorporation of 32P
      phosphates into Ser22, Ser28, and Ser32 by protein kinase A were also observed.
      Protein kinase C incorporated 32P-phosphates into Ser22, Ser23, Ser25, Ser28,
      Ser32, and a threonine residue, but none of these sites could be assigned as a
      major site of phosphorylation. Analyses of the phosphorylated synthetic peptides
      by liquid chromatography-tandem mass spectrometry also showed that protein kinase
      A phosphorylated only one site on peptide S1 and that ions with up to four
      phosphates were detected on peptide S2. Analysis of the data from the tandem ion
      trap mass spectrometry by using the computer program PEPSEARCH did not
      unequivocally identify the specific sites of phosphorylation on these serine-rich
      peptides. Our data suggest that Ser23 is a major protein kinase A-specific
      phosphorylation site on the amino-terminal head region of the NF-M subunit.
      Phosphorylation of Ser23 on the NF-M subunit by protein kinase A may play a
      regulatory role in neurofilament assembly and/or the organization of
      neurofilaments in the axon.

PMID- 9930719
TI  - Dopamine D2-receptor isoforms expressed in AtT20 cells inhibit Q-type high
      voltage-activated Ca2+ channels via a membrane-delimited pathway.
AB  - Dopamine D2 receptors both acutely and chronically inhibit high-voltage-activated
      Ca2+ channels (HVA-CCs). Two alternatively spliced isoforms, D2L (long) and D2S
      (short), are expressed at high levels in rat pituitary intermediate lobe
      melanotropes but are lacking in anterior lobe corticotropes. We stably
      transfected D2L and D2S into corticotrope-derived AtT20 cells. Both isoforms
      coupled to inhibition of Q-type calcium channels through pertussis toxin
      sensitive G proteins. Thus, we have created a model system in which to study the
      kinetics of D2-receptor regulation of Ca2+ channels. Rapid inhibition of HVA-CCs
      was characterized using a novel fluorescence video imaging technique for the
      measurement of millisecond kinetic events. We measured the time elapsed (lag
      time) between the arrival of depolarizing isotonic 66 mM K+, sensed by
      fluorescence from included carboxy-X-rhodamine (CXR), and the beginning of
      increased intracellular Ca2+ levels (sensed by changes in indo 1 fluorescence
      ratio). The lag time averaged 350-550 ms, with no significant differences among
      cell types. Addition of the D2-agonist quinpirole (250 microM) to the K+/CXR
      solution significantly increased the lag times for D2-expressing cells but did
      not alter the lag time for AtT20 controls. The increased lag times for D2L- and
      D2S-transfected cells suggest that at least a fraction of the Ca2+ channels was
      inhibited within the initial 350-550 ms. As this inhibition time is too fast for
      a multistep second messenger pathway, we conclude that inhibition occurs via a
      membrane-delimited diffusion mechanism.

PMID- 9930722
TI  - Relationship of glycosyltransferases and mRNA levels to ganglioside expression in
      neuroblastoma and melanoma cells.
AB  - Most human neuroblastoma tumors are characterized by the high expression of GD2
      (or GD2 and/or GM2) gangliosides, whereas melanomas characteristically express
      GD3 ganglioside. The molecular basis for these patterns was investigated by
      examining the relationship between ganglioside levels, glycosyltransferase
      (GM2/GD2 synthase and GD3 synthase) activity, and corresponding mRNA levels in a
      panel of human neuroblastoma and melanoma cell lines. In general, the ganglioside
      patterns could be explained by the levels of the transferases and their mRNA,
      indicating control at the level of transcription. A key role was noted for GD3
      synthase. Notably, it was found that neuroblastoma cell lines with high GD2
      ganglioside levels had low levels of GD3, its synthase, and mRNA for the enzyme
      even though this step provides the substrate for GD2 synthesis. The key role for
      GD3 synthase was also examined by stably transfecting GD3 synthase cDNA into a
      neuroblastoma cell line (SH-SY5Y) not expressing GD3 and GD2. The resulting cell
      line had high levels of GD2 ganglioside and altered morphology and growth
      characteristics.

PMID- 9930721
TI  - Excitotoxic death of a subset of embryonic rat motor neurons in vitro.
AB  - We have used cultures of purified embryonic rat spinal cord motor neurons to
      study the neurotoxic effects of prolonged ionotropic glutamate receptor
      activation. NMDA and non-NMDA glutamate receptor agonists kill a maximum of 40%
      of the motor neurons in a concentration- and time-dependent manner, which can be
      blocked by receptor subtype-specific antagonists. Subunit-specific antibodies
      stain all of the motor neurons with approximately the same intensity and for the
      same repertoire of subunits, suggesting that the survival of the nonvulnerable
      population is unlikely to be due to the lack of glutamate receptor expression.
      Extracellular Ca2+ is required for excitotoxicity, and the route of entry
      initiated by activation of non-NMDA, but not NMDA, receptors is L-type Ca2+
      channels. Ca2+ imaging of motor neurons after application of specific glutamate
      receptor agonists reveals a sustained rise in intracellular Ca2+ that is present
      to a similar degree in most motor neurons, and can be blocked by appropriate
      receptor/channel antagonists. Although the lethal effects of glutamate receptor
      agonists are seen in only a subset of cultured motor neurons, the basis of this
      selectivity is unlikely to be simply the glutamate receptor phenotype or the
      level/pattern of rise in agonist-evoked intracellular Ca2+.

PMID- 9930723
TI  - Chronic ethanol increases the cannabinoid receptor agonist anandamide and its
      precursor N-arachidonoylphosphatidylethanolamine in SK-N-SH cells.
AB  - In an earlier study, we demonstrated that chronic ethanol (EtOH) exposure down
      regulated the cannabinoid receptors (CB1) in mouse brain synaptic plasma
      membrane. In the present study, we investigated the effect of chronic EtOH on the
      formation of anandamide (AnNH), an endogenous cannabimimetic compound, and its
      precursor N-arachidonoylphosphatidylethanolamine (N-ArPE) in SK-N-SH cells that
      were prelabeled with [3H]arachidonic acid. The results indicate that exposure of
      SK-N-SH cells to EtOH (100 mM) for 72 h significantly increased levels of
      [3H]AnNH and [3H]N-ArPE (p < 0.05) (1.43-fold for [3H]AnNH and 1.65-fold for
      [3H]N-ArPE). Exposure of SK-N-SH cells to EtOH (100 mM, 24 h) inhibited initially
      the formation of [3H]AnNH at 24 h, followed by a progressive increase, reaching a
      statistical significance level at 72 h (p < 0.05). [3H]N-ArPE increased gradually
      to a statistically significant level after 48 and 72 h (p < 0.05). Incubation
      with exogenous ethanolamine (7 mM) and EtOH (100 mM, 72 h) did not result in an
      additive increase in the formation of [3H]AnNH. The formation of [3H]AnNH and
      [3H]N-ArPE by EtOH was enhanced by the Ca2+ ionophore A23187 or by the
      depolarizing agent veratridine and the K+ channel blocker 4-aminopyridine.
      Further, the EtOH-induced formation of [3H]AnNH and [3H]N-ArPE was inhibited by
      exogenous AnNH, whereas only [3H]AnNH formation was inhibited by the CB1 receptor
      antagonist SR141716A and pertussis toxin, suggesting that the CB1 receptor and
      G(i/o) protein mediated the regulation of AnNH levels. The observed increase in
      the levels of these lipids in SK-N-SH cells may be a mechanism for neuronal
      adaptation and may serve as a compensatory mechanism to counteract the continuous
      presence of EtOH. The present observation taken together with our previous
      results indicate the involvement of the endocannabinoid system in mediating some
      of the pharmacological actions of EtOH and may constitute part of a common brain
      pathway mediating reinforcement of drugs of abuse including EtOH.

PMID- 9930724
TI  - Pivotal role of mitochondrial calcium uptake in neural cell apoptosis and
      necrosis.
AB  - Perturbed cellular calcium homeostasis has been implicated in both apoptosis and
      necrosis, but the role of altered mitochondrial calcium handling in the cell
      death process is unclear. The temporal ordering of changes in cytoplasmic
      ([Ca2+]C) and intramitochondrial ([Ca2+]M) calcium levels in relation to
      mitochondrial reactive oxygen species (ROS) accumulation and membrane
      depolarization (MD) was examined in cultured neural cells exposed to either an
      apoptotic (staurosporine; STS) or a necrotic (the toxic aldehyde 4
      hydroxynonenal; HNE) insult. STS and HNE each induced an early increase of
      [Ca2+]C followed by delayed increase of [Ca2+]M. Overexpression of Bcl-2 blocked
      the elevation of [Ca2+]M and the MD in cells exposed to STS but not in cells
      exposed to HNE. The cytoplasmic calcium chelator BAPTA-AM and the inhibitor of
      mitochondrial calcium uptake ruthenium red prevented both apoptosis and necrosis.
      STS and HNE each induced mitochondrial ROS accumulation and MD, which followed
      the increase of [Ca2+]M. Cyclosporin A prevented both apoptosis and necrosis,
      indicating critical roles for MD in both forms of cell death. Caspase activation
      occurred only in cells undergoing apoptosis and preceded increased [Ca2+]M.
      Collectively, these findings suggest that mitochondrial calcium overload is a
      critical event in both apoptotic and necrotic cell death.

PMID- 9930725
TI  - Internalization of G protein-coupled receptors in single olfactory receptor
      neurons.
AB  - Desensitization of many G protein-coupled receptors after ligand binding
      generally involves phosphorylation of the receptors and internalization of the
      ligand-bound, phosphorylated receptors by a clathrin-mediated endocytic pathway.
      Olfactory receptor neurons from the channel catfish (Ictalurus punctatus) express
      the G protein-coupled odorant receptors and metabotropic glutamate receptors. To
      determine whether a clathrin-dependent receptor internalization pathway exists in
      olfactory receptor neurons, western blotting and immunocytochemistry were used to
      identify and localize clathrin and dynamin in isolated olfactory neurons.
      Clathrin and dynamin immunoreactivity was found in the cell bodies, dendrites,
      and dendritic knobs of the neurons. Using the activity-dependent fluorescent dye
      FM1-43 to monitor receptor internalization, we show that single olfactory neurons
      stimulated with the odorant amino acid L-glutamate internalized the dye. Odorant
      stimulated neurons showed a consistent pattern of internalized FM1-43
      fluorescence localized in the cell bodies and dendritic knobs. Odorant-stimulated
      internalization was unaffected by the caveolae activator okadaic acid and was
      significantly decreased by a metabotropic glutamate receptor antagonist,
      suggesting that a functional, clathrin-dependent, receptor-mediated
      internalization pathway exists in olfactory receptor neurons.

PMID- 9930726
TI  - A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's
      amyloid precursor protein.
AB  - Alzheimer amyloid precursor protein (APP) is an integral membrane protein with a
      short cytoplasmic domain of 47 amino acids. It is hoped that identification of
      proteins that interact with the cytoplasmic domain will provide new insights into
      the physiological function of APP and, in turn, into the pathogenesis of
      Alzheimer's disease. To identify proteins that interact with the cytoplasmic
      domain of APP, we employed affinity chromatography using an immobilized synthetic
      peptide corresponding to residues 645-694 of APP695 and identified a protein of
      approximately 130 kDa in rat brain cytosol. Amino acid sequencing of the protein
      revealed the protein to be a rat homologue of monkey UV-DDB (UV-damaged DNA
      binding protein, calculated molecular mass of 127 kDa). UV-DDB/p127 co
      immunoprecipitated with APP using an anti-APP antibody from PC12 cell lysates.
      APP also co-immunoprecipitated with UV-DDB/p127 using an anti-UV-DDB/p127
      antibody. These results indicate that UV-DDB/p127, which is present in the
      cytosolic fraction, forms a complex with APP through its cytoplasmic domain. In
      vitro binding experiments using a glutathione S-transferase-APP cytoplasmic
      domain fusion protein and several mutants indicated that the YENPTY motif within
      the APP cytoplasmic domain, which is important in the internalization of APP and
      amyloid beta protein secretion, may be involved in the interaction between UV
      DDB/p127 and APP.

PMID- 9930727
TI  - Expression of c-fos, c-jun, and c-jun N-terminal kinase (JNK) in a developmental
      model of induced apoptotic death in neurons of the substantia nigra.
AB  - The transcription factors c-fos and c-jun have been proposed to play a role in
      the initiation of programmed cell death in neurons. We have shown that programmed
      cell death, with the morphology of apoptosis, occurs in dopamine neurons of the
      substantia nigra (SN) during normal postnatal development and that this death
      event can be induced by early striatal target injury. We have investigated the
      relationship between c-fos and c-jun protein expression and induced death in
      neurons of the SN. Although c-fos is induced, it is unlikely to play a role in
      cell death, because its expression is not well correlated with apoptotic death
      either temporally or at a cellular level. Expression of c-jun, however, is both
      temporally and regionally correlated with induction of death, and, at a cellular
      level, it colocalizes with apoptotic morphology. The increased expression of c
      jun is likely to be functionally significant, because it is associated with
      increased c-jun N-terminal kinase (JNK) and phosphorylated c-jun expression. JNK
      expression also colocalizes with apoptotic morphology. We conclude that c-jun is
      likely to play a role in the initiation of apoptotic cell death in these neurons.

PMID- 9930729
TI  - Insulin transiently increases tau phosphorylation: involvement of glycogen
      synthase kinase-3beta and Fyn tyrosine kinase.
AB  - The modulation of tau phosphorylation in response to insulin was examined in
      human neuroblastoma SH-SY5Y cells. Insulin treatment resulted in a transient
      increase in tau phosphorylation followed by a decrease in tau phosphorylation
      that correlated directly with a sequential activation and deactivation of
      glycogen synthase kinase-3beta (GSK-3beta). The insulin-induced increase in tau
      phosphorylation and concurrent activation of GSK-3beta was rapid (<2 min) and
      transient, and was associated with increased tyrosine phosphorylation of GSK
      3beta. The increase in GSK-3beta tyrosine phosphorylation corresponded directly
      to an increase in the association of Fyn tyrosine kinase with GSK-3beta, and Fyn
      immunoprecipitated from cells treated with insulin for 1 min phosphorylated GSK
      3beta to a significantly greater extent than Fyn immunoprecipitated from control
      cells. Subsequent to the increase in GSK-3beta activation and tau
      phosphorylation, treatment of cells with insulin for 60 min resulted in a
      dephosphorylation of tau and a decrease in GSK-3beta activity. Thus, insulin
      rapidly and transiently activated GSK-3beta and modulated tau phosphorylation,
      alterations that may contribute to neuronal plasticity.

PMID- 9930728
TI  - Prostaglandin E receptor subtypes in cultured rat microglia and their role in
      reducing lipopolysaccharide-induced interleukin-1beta production.
AB  - Prostaglandins (PGs) are potent modulators of brain function under normal and
      pathological conditions. The diverse effects of PGs are due to the various
      actions of specific receptor subtypes for these prostanoids. Recent work has
      shown that PGE2, while generally considered a proinflammatory molecule, reduces
      microglial activation and thus has an antiinflammatory effect on these cells. To
      gain further insight to the mechanisms by which PGE2 influences the activation of
      microglia, we investigated PGE receptor subtype, i.e., EP1, EP2, EP3, and EP4,
      expression and function in cultured rat microglia. RT-PCR showed the presence of
      the EP1 and EP2 but not EP3 and EP4 receptor subtypes. Sequencing confirmed their
      identity with previously published receptor subtypes. PGE2 and the EP1 agonist 17
      phenyl trinor PGE2 but not the EP3 agonist sulprostone elicited reversible
      intracellular [Ca2+] increases in microglia as measured by fura-2. PGE2 and the
      EP2/EP4-specific agonists 11-deoxy-PGE1 and 19-hydroxy-PGE2 but not the EP4
      selective agonist 1-hydroxy-PGE1 induced dose-dependent production of cyclic AMP
      (cAMP). Interleukin (IL)-1beta production, a marker of activated microglia, was
      also measured following lipopolysaccharide exposure in the presence or absence of
      the receptor subtype agonists. PGE2 and the EP2 agonists reduced IL-1beta
      production. IL-1beta production was unchanged by EP1, EP3, and EP4 agonists. The
      adenylyl cyclase activator forskolin and the cAMP analogue dibutyryl cAMP also
      reduced IL-1beta production. Thus, the inhibitory effects of PGE2 on microglia
      are mediated by the EP2 receptor subtype, and the signaling mechanism of this
      effect is likely via cAMP. These results show that the effects of PGE2 on
      microglia are receptor subtype-specific. Furthermore, they suggest that specific
      and selective manipulation of the effects of PGs on microglia and, as a result,
      brain function may be possible.

PMID- 9930730
TI  - Role of protein kinase C (PKC) in agonist-induced mu-opioid receptor down
      regulation: I. PKC translocation to the membrane of SH-SY5Y neuroblastoma cells
      is induced by mu-opioid agonists.
AB  - Agonist-induced down-regulation of opioid receptors appears to require the
      phosphorylation of the receptor protein. However, the identities of the specific
      protein kinases that perform this task remain uncertain. Protein kinase C (PKC)
      has been shown to catalyze the phosphorylation of several G protein-coupled
      receptors and potentiate their desensitization toward agonists. However, it is
      unknown whether opioid receptor agonists induce PKC activation under
      physiological conditions. Using cultured SH-SY5Y neuroblastoma cells, which
      naturally express mu- and delta-opioid receptors, we investigated whether mu
      opioid receptor agonists can activate PKC by measuring enzyme translocation to
      the membrane fraction. PKC translocation and opioid receptor densities were
      simultaneously measured by 3H-phorbol ester and [3H]diprenorphine binding,
      respectively, to correlate alterations in PKC localization with changes in
      receptor binding sites. We observed that mu-opioid agonists have a dual effect on
      membrane PKC density depending on the period of drug exposure. Exposure for 2-6 h
      to [D-Ala2,N-Me-Phe4,Gly-ol]enkephalin or morphine promotes the translocation of
      PKC from the cytosol to the plasma membrane. Longer periods of opioid exposure
      (>12 h) produce a decrease in membrane-bound PKC density to a level well below
      basal. A significant decrease in [3H]diprenorphine binding sites is first
      observed at 2 h and continues to decline through the last time point measured (48
      h). The opioid receptor antagonist naloxone attenuated both opioid-mediated PKC
      translocation and receptor down-regulation. These results demonstrate that
      opioids are capable of activating PKC, as evidenced by enhanced translocation of
      the enzyme to the cell membrane, and this finding suggests that PKC may have a
      physiological role in opioid receptor plasticity.

PMID- 9930731
TI  - Role of protein kinase C (PKC) in agonist-induced mu-opioid receptor down
      regulation: II. Activation and involvement of the alpha, epsilon, and zeta
      isoforms of PKC.
AB  - Phosphorylation of specific amino acid residues is believed to be crucial for the
      agonist-induced regulation of several G protein-coupled receptors. This is
      especially true for the three types of opioid receptors (mu, delta, and kappa),
      which contain consensus sites for phosphorylation by numerous protein kinases.
      Protein kinase C (PKC) has been shown to catalyze the in vitro phosphorylation of
      mu- and delta-opioid receptors and to potentiate agonist-induced receptor
      desensitization. In this series of experiments, we continue our investigation of
      how opioid-activated PKC contributes to homologous receptor down-regulation and
      then expand our focus to include the exploration of the mechanism(s) by which mu
      opioids produce PKC translocation in SH-SY5Y neuroblastoma cells. [D-Ala2,N-Me
      Phe4,Gly-ol]enkephalin (DAMGO)-induced PKC translocation follows a time-dependent
      and biphasic pattern beginning 2 h after opioid addition, when a pronounced
      translocation of PKC to the plasma membrane occurs. When opioid exposure is
      lengthened to >12 h, both cytosolic and particulate PKC levels drop significantly
      below those of control-treated cells in a process we termed "reverse
      translocation." The opioid receptor antagonist naloxone, the PKC inhibitor
      chelerythrine, and the L-type calcium channel antagonist nimodipine attenuated
      opioid-mediated effects on PKC and mu-receptor down-regulation, suggesting that
      this is a process partially regulated by Ca2+-dependent PKC isoforms. However,
      chronic exposure to phorbol ester, which depletes the cells of diacylglycerol
      (DAG) and Ca2+-sensitive PKC isoforms, before DAMGO exposure, had no effect on
      opioid receptor down-regulation. In addition to expressing conventional (PKC
      alpha) and novel (PKC-epsilon) isoforms, SH-SY5Y cells also contain a DAG- and
      Ca2+-independent, atypical PKC isozyme (PKC-zeta), which does not decrease in
      expression after prolonged DAMGO or phorbol ester treatment. This led us to
      investigate whether PKC-zeta is similarly sensitive to activation by mu-opioids.
      PKC-zeta translocates from the cytosol to the membrane with kinetics similar to
      those of PKC-alpha and epsilon in response to DAMGO but does not undergo reverse
      translocation after longer exposure times. Our evidence suggests that direct PKC
      activation by mu-opioid agonists is involved in the processes that result in mu
      receptor down-regulation in human neuroblastoma cells and that conventional,
      novel, and atypical PKC isozymes are involved.

PMID- 9930732
TI  - Effects of cyclin-dependent kinase inhibitors on transcription and ocular
      circadian rhythm of Aplysia.
AB  - Cyclin-dependent kinases (CDKs) mediate cell-cycle phase transitions. Recently,
      CDKs have been associated with non-cell-cycle roles such as DNA repair,
      transcription, and phosphate metabolism in yeast. The cyclical processes,
      circadian rhythms and the eukaryotic cell cycle, are similar in many respects. It
      is possible that a kinase like CDK is involved in the control of circadian
      rhythms. In this study, the effects of CDK inhibitors (olomoucine, roscovitine,
      and butyrolactone I) on the Aplysia ocular circadian rhythm were investigated.
      Continuous treatments with olomoucine (10 microM) lengthened the free-running
      period of the rhythm, and pulse treatments of olomoucine (6 h, 100 microM)
      delayed the rhythm. The effects of olomoucine on the rhythm were qualitatively
      similar to those of a reversible inhibitor of transcription, 5,6-dichloro-beta-1
      ribobenzimidazole. Subsequently, olomoucine was found to inhibit RNA synthesis in
      the eye of Aplysia and Bulla. All of the other CDK inhibitors used in this study
      also inhibited transcription in the eye of Aplysia, and their effects on
      transcription correlated with their effects on the circadian rhythm. This study
      adds substantial evidence to that previously obtained by using 5,6-dichloro-beta
      1-ribobenzimidazole for a role of transcription in the mechanism responsible for
      circadian rhythmicity in the eye of Aplysia. Also, these results indicate that
      caution is warranted in interpreting results obtained by using CDK inhibitors,
      because these drugs appear to inhibit transcription as well as CDKs.

PMID- 9930733
TI  - Differential phosphorylation of syntaxin and synaptosome-associated protein of 25
      kDa (SNAP-25) isoforms.
AB  - The synaptic plasma membrane proteins syntaxin and synaptosome-associated protein
      of 25 kDa (SNAP-25) are central participants in synaptic vesicle trafficking and
      neurotransmitter release. Together with the synaptic vesicle protein
      synaptobrevin/vesicle-associated membrane protein (VAMP), they serve as receptors
      for the general membrane trafficking factors N-ethylmaleimide-sensitive factor
      (NSF) and soluble NSF attachment protein (alpha-SNAP). Consequently, syntaxin,
      SNAP-25, and VAMP (and their isoforms in other membrane trafficking pathways)
      have been termed SNAP receptors (SNAREs). Because protein phosphorylation is a
      common and important mechanism for regulating a variety of cellular processes,
      including synaptic transmission, we have investigated the ability of syntaxin and
      SNAP-25 isoforms to serve as substrates for a variety of serine/threonine protein
      kinases. Syntaxins 1 A and 4 were phosphorylated by casein kinase II, whereas
      syntaxin 3 and SNAP-25 were phosphorylated by Ca2+- and calmodulin-dependent
      protein kinase II and cyclic AMP-dependent protein kinase, respectively. The
      biochemical consequences of SNARE protein phosphorylation included a reduced
      interaction between SNAP-25 and phosphorylated syntaxin 4 and an enhanced
      interaction between phosphorylated syntaxin 1A and the synaptic vesicle protein
      synaptotagmin I, a potential Ca2+ sensor in triggering synaptic vesicle
      exocytosis. No other effects on the formation of SNARE complexes (comprised of
      syntaxin, SNAP-25, and VAMP) or interactions involving n-Sec1 or alpha-SNAP were
      observed. These findings suggest that although phosphorylation does not directly
      regulate the assembly of the synaptic SNARE complex, it may serve to modulate
      SNARE complex function through other proteins, including synaptotagmin I.

PMID- 9930734
TI  - The pH-sensitive dye acridine orange as a tool to monitor exocytosis/endocytosis
      in synaptosomes.
AB  - We introduce the use of the pH-sensitive dye acridine orange (AO) to monitor
      exo/endocytosis of acidic neurotransmitter-containing vesicles in synaptosomes.
      AO is accumulated exclusively in acidic v-ATPase-dependent bafilomycin (Baf)
      sensitive compartments. A fraction of the accumulated AO is rapidly released
      (fluorescence increase) upon depolarization with KCl in the presence of Ca2+. The
      release (completed in 5-6 s) is followed by reuptake to values below the
      predepolarization baseline. The reuptake, but not the release, is inhibited by
      Baf added 5 s prior to KCl. In a similar protocol, Baf does not affect the
      initial fast phase of glutamate release measured enzymatically, but it abolishes
      the subsequent slow phase. Thus, the fast AO release corresponds to the rapid
      phase of glutamate release and the slow phase depends on vesicle cycling. AO
      reuptake depends in part on the progressive accumulation of acid-loaded vesicles
      during cycling. Stopping exocytosis at selected times after KCl by Ca2+ removal
      with EGTA evidences endocytosis: Its T(1/2) was 12 +/- 0.6 s. The K(A)+, channel
      inhibitors 4-aminopyridine (100 microM) and alpha-dendrotoxin (10-100 nM) are
      known to induce glutamate release by inducing the firing of Na+ channels; their
      action is potentiated by the activation of protein kinase C. Also these agents
      promote a Ca2+-dependent AO release, which is prevented by the Na+ channel
      inhibitor tetrodotoxin and potentiated by 4beta-phorbol 12-myristate 13-acetate
      (PMA). With alpha-dendrotoxin, endocytosis was monitored by stopping exocytosis
      at selected times with EGTA or alternatively with Cd2+ or tetrodotoxin. The
      T(1/2) of endocytosis, which was unaffected by PMA, was 12 +/- 0.4 s with EGTA
      and Cd2+ and 9.5 +/- 0.5 s with tetrodotoxin. Protein kinase C activation
      appeared to facilitate vesicle turnover.

PMID- 9930735
TI  - Inhibition of calcium-dependent NMDA receptor current rundown by calbindin-D28k.
AB  - NMDA receptors are regulated by several different calcium-dependent processes. To
      determine if the presence of the intracellular calcium-binding protein calbindin
      D28k can influence the calcium regulation of NMDA receptor activity, human
      embryonic kidney 293 cells were co-transfected with cDNAs for NMDA receptor
      subunits and calbindin. Recordings were made using the nystatin perforated patch
      technique to preserve intracellular contents. When compared with control cells
      (transfected with cDNA encoding beta-galactosidase in place of calbindin), the
      presence of calbindin had no effect on either calcium-dependent inactivation or
      the calcium-sensitive, time-dependent increase in glycine-independent
      desensitization of NMDA receptor-mediated currents. However, the development of
      calcium-dependent rundown of peak glutamate-evoked current was slowed
      significantly in calbindin versus beta-galactosidase co-transfected cells. This
      result was true for cells transfected with either NR1/NR2A or NR1/NR2B subunits,
      although calbindin was relatively less effective at inhibiting rundown in
      NR1/NR2B-expressing cells. NMDA peak current rundown has been attributed to
      calcium-induced depolymerization of the actin cytoskeleton. Therefore, our
      results indicate that although calbindin may not influence calcium-dependent
      regulatory processes occurring very near the NMDA receptor channel, it appears to
      be more effective at buffering local elevations in intracellular calcium at the
      actin cytoskeleton.

PMID- 9930736
TI  - 2-Oxoacids regulate kynurenic acid production in the rat brain: studies in vitro
      and in vivo.
AB  - This study was designed to examine the role of 2-oxoacids in the enzymatic
      transamination of L-kynurenine to the excitatory amino acid receptor antagonist,
      kynurenate, in the rat brain. In brain tissue slices incubated in Krebs-Ringer
      buffer with a physiological concentration of L-kynurenine, pyruvate, and several
      other straight- and branched-chain 2-oxoacids, substantially restored basal
      kynurenate production in a dose-dependent manner without increasing the
      intracellular concentration of L-kynurenine. All 2-oxoacids tested also reversed
      or attenuated the hypoglycemia-induced decrease in kynurenate synthesis, but only
      pyruvate and oxaloacetate also substantially restored intracellular L-kynurenine
      accumulation. Thus, 2-oxoacids increase kynurenate formation in the brain
      primarily by functioning as co-substrates of the transamination reaction. This
      was supported further by the fact that the nonspecific kynurenine
      aminotransferase inhibitors (aminooxy)acetic acid and dichlorovinylcysteine
      prevented the effect of pyruvate on kynurenate production in a dose-dependent
      manner. Moreover, all 2-oxoacids tested attenuated or prevented the effects of
      veratridine, quisqualate, or L-alpha-aminoadipate, which reduce the
      transamination of L-kynurenine to kynurenate. Finally, dose-dependent increases
      in extracellular kynurenate levels in response to an intracerebral perfusion with
      pyruvate or alpha-ketoisocaproate were demonstrated by in vivo microdialysis.
      Taken together, these data show that 2-oxoacids can directly augment the de novo
      production of kynurenate in several areas of the rat brain. 2-Oxoacids may
      therefore provide a novel pharmacological approach for the manipulation of
      excitatory amino acid receptor function and dysfunction.

PMID- 9930737
TI  - The bacterial endotoxin lipopolysaccharide causes rapid inappropriate excitation
      in rat cortex.
AB  - There is mounting evidence that inflammation and associated excitotoxicity may
      play important roles in various neurodegenerative disorders, such as bacterial
      infections, Alzheimer's disease, AIDS dementia, and multiple sclerosis. The
      immunogen E. coli lipopolysaccharide (LPS, endotoxin) has been widely used to
      stimulate immune/inflammatory responses both systemically and in the CNS. Here,
      we show that exposure of parietal cortical slices from adult rats to LPS
      triggered very rapid (<2.5 min) and sustained releases of the neurotransmitters
      glutamate and noradrenaline, and of the neuromodulator adenosine. The responses
      to LPS declined rapidly following removal of the LPS and exhibited no
      tachyphylaxis to repeated exposures to LPS. The detoxified form of LPS had no
      effect. LPS-evoked release of [3H]noradrenaline, but not of glutamate or
      adenosine, appears to be partly due to the released glutamate acting at
      ionotropic receptors on the noradrenergic axons present in the cortical slices.
      LPS appears to release glutamate, which then acts at non-NMDA receptors to remove
      the voltage-sensitive Mg2+ block of NMDA receptors, thus permitting NMDA
      receptors to be activated and noradrenaline release to proceed. It seems possible
      that rapid, inappropriate excitation may occur in the immediate vicinity of gram
      negative bacterial infections in the brain. If similar inappropriate excitations
      are also triggered by those immunogens specifically associated with Alzheimer's
      disease (beta-amyloid), AIDS dementia (gp120 and gp41), or multiple sclerosis
      (myelin basic protein), they might explain some of the acute, transient
      neurological and psychiatric symptoms associated with these disorders.

PMID- 9930738
TI  - Differential regional effects of methamphetamine on the activities of tryptophan
      and tyrosine hydroxylase.
AB  - Administration of high doses of methamphetamine (METH) produces both short- and
      long-term enzymatic deficits in central monoaminergic systems. To determine
      whether a correlative relationship exists between these acute and long-term
      consequences of METH treatment, in the present study we examined the regional
      effects of METH on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH)
      activities in various regions of the caudate nucleus, nucleus accumbens, and
      globus pallidus. A single METH administration decreased TPH activity 1 h after
      treatment in the globus pallidus, in the nucleus accumbens, and throughout the
      caudate; in the anterior caudate, the ventral-medial was more affected than the
      dorsal-lateral region. In contrast, TH activity was not decreased in either the
      caudate or the globus pallidus after a single METH administration; however, it
      was altered in the nucleus accumbens. Seven days after multiple METH
      administrations, TH and TPH activities were decreased in most caudate regions but
      not in the nucleus accumbens or globus pallidus. These data demonstrate that (1)
      the effects of METH on TPH and TH vary regionally; and (2) the short-term and
      long-term regional responses of TPH to METH in the caudate and globus pallidus
      correlated. In contrast, METH-induced acute TH responses did not predict the long
      term changes in TH activity.

PMID- 9930739
TI  - GTP cyclohydrolase I feedback regulatory protein is expressed in serotonin
      neurons and regulates tetrahydrobiopterin biosynthesis.
AB  - Tetrahydrobiopterin, the coenzyme required for hydroxylation of phenylalanine,
      tyrosine, and tryptophan, regulates its own synthesis through feedback inhibition
      of GTP cyclohydrolase I (GTPCH) mediated by a regulatory subunit, the GTP
      cyclohydrolase feedback regulatory protein (GFRP). In the liver, L-phenylalanine
      specifically stimulates tetrahydrobiopterin synthesis by displacing
      tetrahydrobiopterin from the GTPCH-GFRP complex. To explore the role of this
      regulatory system in rat brain, we examined the localization of GFRP mRNA using
      double-label in situ hybridization. GFRP mRNA expression was abundant in
      serotonin neurons of the dorsal raphe nucleus but was undetectable in dopamine
      neurons of the midbrain or norepinephrine neurons of the locus coeruleus.
      Simultaneous nuclease protection assays for GFRP and GTPCH mRNAs showed that GFRP
      mRNA is most abundant within the brainstem and that the ratio of GFRP to GTPCH
      mRNA is much higher than in the ventral midbrain. Two species of GFRP mRNA
      differing by approximately 20 nucleotides in length were detected in brainstem
      but not in other tissues, with the longer, more abundant form being common to
      other brain regions. It is interesting that the pineal and adrenal glands did not
      contain detectable levels of GFRP mRNA, although GTPCH mRNA was abundant in both.
      Primary neuronal cultures were used to examine the role of GFRP-mediated
      regulation of GTPCH on tetrahydrobiopterin synthesis within brainstem serotonin
      neurons and midbrain dopamine neurons. L-Phenylalanine increased
      tetrahydrobiopterin levels in serotonin neurons to a maximum of twofold in a
      concentration-dependent manner, whereas D-phenylalanine and L-tryptophan were
      without effect. In contrast, tetrahydrobiopterin levels within cultured dopamine
      neurons were not altered by L-phenylalanine. The time course of this effect was
      very rapid, with a maximal response observed within 60 min. Inhibitors of
      tetrahydrobiopterin biosynthesis prevented the L-phenylalanine-induced increase
      in tetrahydrobiopterin levels. 7,8-Dihydroneopterin, a reduced pteridine capable
      of inhibiting GTPCH in a GFRP-dependent manner, decreased tetrahydrobiopterin
      levels in cultures of both serotonin and dopamine neurons. This inhibition was
      reversed by L-phenylalanine in serotonin but not in dopamine neurons. Our data
      suggest that GTPCH activity within serotonin neurons is under a tonic inhibitory
      tone mediated by GFRP and that tetrahydrobiopterin levels are maintained by the
      balance of intracellular concentrations of tetrahydrobiopterin and L
      phenylalanine. In contrast, although tetrahydrobiopterin biosynthesis within
      dopamine neurons is also feedback-regulated, L-phenylalanine plays no role, and
      therefore tetrahydrobiopterin may have a direct effect on GTPCH activity.

PMID- 9930740
TI  - Formation of N-pyroglutamyl peptides from N-Glu and N-Gln precursors in Aplysia
      neurons.
AB  - Matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry
      is used to examine the formation of N-pyroglutamate (pGlu) in single, identified
      neurons from Aplysia. Six pGlu peptides are identified in the R3-14 and the R15
      neurons that result from in vivo processing of peptides containing either Glu or
      Gln at their respective N-termini. Moreover, we show that Glu-derived pGlu is not
      a sample collection or measurement artifact. The pGlu peptides are detected in
      isolated cell bodies, regenerated neurites in culture, interganglionic connective
      nerves, cell homogenates, and collected releasates. We also demonstrate that R3
      14 cells readily convert a synthetic N-Glu peptide to its pGlu analogue,
      indicating the presence of novel enzymatic activity.

PMID- 9930741
TI  - Differential regulation of striatal preproenkephalin and preprotachykinin mRNA
      levels in MPTP-lesioned monkeys chronically treated with dopamine D1 or D2
      receptor agonists.
AB  - Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys
      and in parkinsonian patients show elevated preproenkephalin (PPE) mRNA levels,
      unaltered by chronic L-DOPA therapy, whereas preprotachykinin (PPT) mRNA levels
      are decreased by the lesion and corrected by L-DOPA. The relative contributions
      of the dopamine D1 and D2 receptors for PPE mRNA regulation were investigated in
      the present study and compared with those for PPT mRNA. In situ hybridization was
      used to measure peptide mRNA levels in the striatum of MPTP cynomolgus monkeys
      after chronic 1-month treatment with the D1 agonist SKF-82958, administered
      subcutaneously in pulsatile or continuous mode, compared with the long-acting D2
      agonist cabergoline. Normal as well as untreated MPTP animals were also studied.
      PPE mRNA levels were elevated in the caudate nucleus and putamen of untreated
      MPTP monkeys compared with control animals with a more pronounced increase in the
      lateral as compared with the medial part of both structures. PPT mRNA levels
      showed a rostrocaudal gradient, with higher values in the middle of the caudate
      putamen and more so in the medial versus the lateral parts. PPT mRNA levels were
      decreased in the caudate and putamen of untreated MPTP monkeys compared with
      control animals, and this was observed in the middle and posterior parts of these
      brain areas. Elevated PPE and decreased PPT mRNA levels observed after MPTP
      exposure were corrected after treatment with cabergoline (0.25 mg/kg, every other
      day), a dose that had antiparkinsonian effects and did not give sustained
      dyskinesia. In contrast, elevated PPE mRNA levels observed in untreated MPTP
      monkeys were markedly increased by pulsatile administration of SKF-82958 (1
      mg/kg, three times daily) in two monkeys in which the parkinsonian symptoms were
      improved and dyskinesias developed, whereas it remained close to control values
      in a third one that did not display dyskinesias despite a sustained improvement
      in disability; a shorter duration of motor benefit (wearing off) over time was
      observed in these three animals. By contrast, pulsatile administration of SKF
      82958 corrected the decreased PPT level observed in untreated MPTP monkeys.
      Continuous treatment with SKF-82958 (equivalent daily dose) produced no clear
      antiparkinsonian and dyskinetic responses and did not alter the denervation
      induced elevation of PPE or decrease of PPT mRNA levels. The present data suggest
      an opposite contribution of the dopamine D1 receptors (stimulatory) as compared
      with the dopamine D2 receptors (inhibitory) on PPE mRNA, whereas a similar
      stimulatory contribution of D1 or D2 receptors is observed for PPT mRNA. An
      increase in PPE expression could be involved in the induction of dyskinesias and
      wearing off, whereas our data do not support this link for PPT. The
      antiparkinsonian response was associated with a correction of the lesion-induced
      decrease of PPT.

PMID- 9930742
TI  - Up-regulation of protein chaperones preserves viability of cells expressing toxic
      Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis.
AB  - Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial
      cases of amyotrophic lateral sclerosis, a neurodegenerative disorder
      characterized by loss of cortical, brainstem, and spinal motor neurons. We
      present evidence that SOD-1 mutants alter the activity of molecular chaperones
      that aid in proper protein folding and targeting of abnormal proteins for
      degradation. In a cultured cell line (NIH 3T3), resistance to mutant SOD-1
      toxicity correlated with increased overall chaperoning activity (measured by the
      ability of cytosolic extracts to prevent heat denaturation of catalase) as well
      as with up-regulation of individual chaperones/stress proteins. In transgenic
      mice expressing human SOD-1 with the G93A mutation, chaperoning activity was
      decreased in lumbar spinal cord but increased or unchanged in clinically
      unaffected tissues. Increasing the level of the stress-inducible chaperone 70-kDa
      heat shock protein by gene transfer reduced formation of mutant SOD-containing
      proteinaceous aggregates in cultured primary motor neurons expressing G93A SOD-1
      and prolonged their survival. We propose that insufficiency of molecular
      chaperones may be directly involved in loss of motor neurons in this disease.

PMID- 9930743
TI  - Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's
      disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change?
AB  - Controversy exists as to the clinical importance, cause, and disease specificity
      of the cytochrome oxidase (CO) activity reduction observed in some patients with
      Alzheimer's disease (AD). Although it is assumed that the enzyme is present in
      normal amount in AD, no direct measurements of specific CO protein subunits have
      been conducted. We measured protein levels of CO subunits encoded by
      mitochondrial (COX I, COX II) and nuclear (COX IV, COX VIc) DNA in autopsied
      brain of patients with AD whom we previously reported had decreased cerebral
      cortical CO activity. To assess disease specificity, groups of patients with
      spinocerebellar ataxia type I and Friedreich's ataxia were also included. As
      compared with the controls, mean protein concentrations of all four CO subunits
      were significantly decreased (-19 to -47%) in temporal and parietal cortices in
      the AD group but were not significantly reduced (-12 to -17%) in occipital
      cortex. The magnitude of the reduction in protein levels of the CO subunits
      encoded by mitochondrial DNA (-42 to -47%) generally exceeded that encoded by
      nuclear DNA (-19 to -43%). In the spinocerebellar ataxia disorders, COX I and COX
      II levels were significantly decreased in cerebellar cortex (-22 to -32%) but
      were normal or close to normal in cerebral cortex, an area relatively unaffected
      by neurodegeneration. We conclude that protein levels of mitochondrial- and
      nuclear-encoded CO subunits are moderately reduced in degenerating but not in
      relatively spared brain areas in AD and that the decrease is not specific to this
      disorder. The simplest explanation for our findings is that CO is decreased in
      human brain disorders as a secondary event in brain areas having reduced neuronal
      activity or neuronal/synaptic elements consequent to the primary
      neurodegenerative process.

PMID- 9930744
TI  - Regulation of hemopexin synthesis in degenerating and regenerating rat sciatic
      nerve.
AB  - In injured peripheral nerves, hemopexin mRNA is expressed by fibroblasts, Schwann
      cells, and invading blood macrophages, and the protein accumulates in the
      extracellular matrix. This and its absence of regulation in injured central optic
      nerve suggest that hemopexin could play a positive role in peripheral nerve
      repair. Here, we studied the regulation of hemopexin expression in degenerating
      and regenerating nerves. After a sciatic nerve injury, both the synthesis of
      hemopexin and the level of its mRNA increase sharply during the first 2 days,
      leading to an accumulation of hemopexin in the nerve. Afterward, hemopexin
      expression decreases progressively in regenerating nerves. In permanently
      degenerated nerves, it is again transiently increased and then strongly
      decreased, whereas hemopexin from blood origin is accumulating. As part of the
      elucidation of the complex regulation of hemopexin expression in injured nerves,
      we demonstrate that interleukin-6 increases hemopexin synthesis in intact nerves,
      whereas adult rat serum, but not purified hemopexin, inhibits it in degenerated
      nerves. Hemopexin, known as acute-phase protein, is therefore one of the
      molecules rapidly and specifically up-regulated in injured peripheral nerves.
      More generally, our findings suggest that the acute phase could be not only a
      systemic liver-specific response but also a reaction of injured tissues
      themselves.

PMID- 9930746
TI  - Regional differences in striatal dopamine uptake and release associated with
      recovery from MPTP-induced parkinsonism: an in vivo electrochemical study.
AB  - This study directly assessed striatal dopamine (DA) uptake rates and peak release
      in response to KCl in normal, symptomatic, and recovered 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-treated cats using in vivo electrochemistry. DA
      uptake rates measured after direct application of known concentrations of DA to
      the striatum were slowed significantly in both dorsal and ventral striatum in
      symptomatic cats compared with rates recorded in normal animals. DA uptake rates
      remained significantly slowed in recovered cats and were not significantly
      different from the rates recorded in symptomatic animals. In symptomatic cats,
      both DA uptake rates and the signal recorded in response to KCl stimulation were
      significantly decreased from normal in all dorsal and ventral striatal regions
      sampled. Reduction/oxidation (redox) ratios recorded in response to KCl
      stimulation suggested DA to be the predominant electroactive species. In
      spontaneously recovered MPTP-treated cats, recordings in the ventral striatum
      subsequent to KCl stimulation again suggested DA to be the predominant
      electroactive species released, and peak levels were significantly higher than
      those recorded in symptomatic animals. In the dorsal striatum of recovered cats,
      redox ratios recorded subsequent to KCl stimulation suggested serotonin rather
      than DA to be the predominant electroactive species released. Peak levels of
      release in the dorsal striatum were not significantly greater than those recorded
      in symptomatic animals. These results suggest that in spontaneously recovered
      MPTP-treated cats, there is partial recovery of ventral striatal DAergic
      terminals, persistent loss of dorsal striatal DAergic terminals, and a down
      regulation of DA transporter number/function throughout the striatum. These
      processes may contribute to volume transmission of DA in the striatum and promote
      functional recovery.

PMID- 9930745
TI  - Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons.
AB  - Riluzole is used clinically in patients with amyotrophic lateral sclerosis. As
      oxidative stress, in addition to excitotoxicity, may be a major mechanism of
      motoneuron degeneration in patients with amyotrophic lateral sclerosis, we
      examined whether riluzole protects against nonexcitotoxic oxidative injury.
      Probably reflecting its weak antiexcitotoxic effects, riluzole (1-30 microM)
      attenuated submaximal neuronal death induced by 24-h exposure to 30 microM
      kainate or NMDA, but not that by 100 microM NMDA, in cortical cultures. Riluzole
      also attenuated nonexcitotoxic oxidative injury induced by exposure to FeCl3 in
      the presence of MK-801 and CNQX. Consistent with its antioxidative effects,
      riluzole reduced Fe3+-induced lipid peroxidation, and inhibited cytosolic
      phospholipase A2. By contrast, riluzole did not attenuate neuronal apoptosis
      induced by staurosporine. Rather unexpectedly, 24-48-h exposure to 100-300 microM
      riluzole induced neuronal death accompanied by nuclear and DNA fragmentations,
      which was attenuated by caspase inhibitor carbobenzyloxy-Val-Ala-Asp-fluoromethyl
      ketone but not by protein synthesis inhibitor cycloheximide. The present study
      demonstrates that riluzole has direct antioxidative actions, perhaps in part by
      inhibiting phospholipase A2. However, in the same neurons, riluzole paradoxically
      induces neuronal apoptosis in a caspase-sensitive manner. Considering current
      clinical use of riluzole, further studies are warranted to investigate its
      potential cytolethal effects.

PMID- 9930747
TI  - F4-isoprostanes as specific marker of docosahexaenoic acid peroxidation in
      Alzheimer's disease.
AB  - F2-isoprostanes are prostaglandin-like compounds derived from free radical
      catalysed peroxidation of arachidonic acid. Peroxidation of eicosapentaenoic acid
      produces F3-isoprostanes, whereas peroxidation of docosahexaenoic acid would give
      F4-isoprostanes. This study demonstrates the presence of esterified F4
      isoprostanes in human brain and shows that levels are elevated in certain brain
      cortex regions in Alzheimer's disease. Our data with Alzheimer's disease suggest
      that analysis of F4-isoprostanes will provide new opportunities to study lipid
      peroxidation in the neurodegenerative diseases.

PMID- 9930748
TI  - Quantification of axonal damage in traumatic brain injury: affinity purification
      and characterization of cerebrospinal fluid tau proteins.
AB  - Diffuse axonal injury is a primary feature of head trauma and is one of the most
      frequent causes of mortality and morbidity. Diffuse axonal injury is microscopic
      in nature and difficult or impossible to detect with imaging techniques. The
      objective of the present study was to determine whether axonal injury in head
      trauma patients could be quantified by measuring levels of CSF tau proteins. Tau
      proteins are structural microtubule binding proteins primarily localized in the
      axonal compartment of neurons. Monoclonal antibodies recognizing the form of tau
      found in the CSF of head trauma patients were developed by differential CSF
      hybridoma screening using CSF from head trauma and control patients. Clones
      positive for head trauma CSF tau proteins were used to characterize this form of
      tau and for ELISA development. Using the developed ELISA, CSF tau levels were
      elevated >1,000-fold in head trauma patients (mean, 1,519 ng/ml of CSF) when
      compared with patients with multiple sclerosis (mean, 0.014 ng/ml of CSF; p <
      0.001), normal pressure hydrocephalus (nondetectable CSF tau), neurologic
      controls (mean, 0.031 ng/ml of CSF; p < 0.001), or nonneurologic controls
      (nondetectable CSF tau; p < 0.001). In head trauma, a relationship between
      clinical improvement and decreased CSF tau levels was observed. These data
      suggest that CSF tau levels may prove a clinically useful assay for quantifying
      the axonal injury associated with head trauma and monitoring efficacy of
      neuroprotective agents. Affinity purification of CSF tau from head trauma
      patients indicated a uniform cleavage of approximately 18 kDa from all six tau
      isoforms, reducing their apparent molecular sizes to 30-50 kDa. These cleaved
      forms of CSF tau consisted of the interior portion of the tau sequence, including
      the microtubule binding domain, as judged by cyanogen bromide digestion.
      Consistent with these data, CSF cleaved tau bound taxol-polymerized microtubules,
      indicating a functionally intact microtubule binding domain. Furthermore, epitope
      mapping studies suggested that CSF cleaved tau proteins consist of the interior
      portion of the tau sequence with cleavage at both N and C terminals.

PMID- 9930749
TI  - Protein-bound acrolein: a novel marker of oxidative stress in Alzheimer's
      disease.
AB  - Several lines of evidence support the role of oxidative stress, including
      increased lipid peroxidation, in the pathogenesis of Alzheimer's disease (AD).
      Lipid peroxidation generates various reactive aldehydes, such as 4-hydroxynonenal
      (HNE), which have been detected immunochemically in AD, particularly in
      neurofibrillary tangles, one of the major diagnostic lesions in AD brains. A
      recent study demonstrated that acrolein, the most reactive among the alpha,beta
      unsaturated aldehyde products of lipid peroxidation, could be rapidly
      incorporated into proteins, generating a carbonyl derivative, a marker of
      oxidative stress to proteins. The current studies used an antibody raised against
      acrolein-modified keyhole limpet hemocyanin (KLH) to test whether acrolein
      modification of proteins occurs in AD. Double immunofluorescence revealed strong
      acrolein-KLH immunoreactivity in more than half of all paired helical filament
      (PHF)-1-labeled neurofibrillary tangles in AD cases. Acrolein-KLH
      immunoreactivity was also evident in a few neurons lacking PHF-1-positive
      neurofibrillary tangles. Light acrolein-KLH immunoreactivity occurred in
      dystrophic neurites surrounding the amyloid-beta core, which itself lacked
      acrolein-KLH staining. The pattern of acrolein-KLH immunostaining was similar to
      that of HNE. Control brains did not contain any acrolein-KLH-immunoreactive
      structures. The current results suggest that protein-bound acrolein is a powerful
      marker of oxidative damage to protein and support the hypothesis that lipid
      peroxidation and oxidative damage to protein may play a crucial role in the
      formation of neurofibrillary tangles and to neuronal death in AD.

PMID- 9930750
TI  - GTP cyclohydrolase I gene expression in the brains of male and female hph-1 mice.
AB  - The hph-1 mouse is characterized by low levels of GTP cyclohydrolase I (GTPCH)
      and tetrahydrobiopterin. A quantitative double-label in situ hybridization
      technique was used to examine CNS GTPCH mRNA expression within serotonin,
      dopamine, and norepinephrine neurons of male and female wild-type and hph-1 mice.
      In wild-type male and female animals the highest levels of GTPCH mRNA expression
      were observed within serotonin neurons, followed by norepinephrine and then
      dopamine neurons. Wild-type female animals were found to express lower levels of
      GTPCH mRNA in each cell type when compared with levels seen in wild-type males.
      GTPCH mRNA abundance in all three cell types was lower in hph-1 male than in wild
      type male mice, with the greatest reduction in serotonin neurons. GTPCH mRNA
      levels were also lower in hph-1 female than in wild-type female mice, again with
      the greatest reduction occurring in serotonin neurons. Comparison of hph-1 male
      and hph-1 female mice revealed that the sex-linked difference in GTPCH mRNA
      expression observed in wild-type neurons was only present within female dopamine
      neurons. Overall, these results indicate that not only are basal levels of GTPCH
      mRNA expression heterogeneous across wild-type murine monoamine cell types but
      that gene expression is also modified in a sex-linked and cell-specific fashion
      by the hph-1 gene locus. The hph-1 mutation does not lie within the GTPCH mRNA
      coding region. The 5' flanking region of the GTPCH gene was cloned and sequenced
      and shown to be identical for both wild-type and hph-1 genomic DNA. Transient
      transfection assays performed in PC12 cells demonstrated that this 5' flanking
      region was sufficient to initiate transcription of a luciferase reporter gene.
      Although the hph-1 mutation does not lie within the 5' flanking region of the
      GTPCH gene, this region of the gene can function as a core promoter and is thus
      crucial to the control of GTPCH gene expression.

PMID- 9930751
TI  - Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema,
      ischemic injury volume, and tissue polyamine levels in rats after temporary
      middle cerebral artery occlusion.
AB  - The possible effects of the polyamine interconversion pathway on tissue polyamine
      levels, brain edema formation, and ischemic injury volume were studied by using a
      selective irreversible inhibitor, MDL 72527, of the interconversion pathway
      enzyme, polyamine oxidase. In an intraluminal suture occlusion model of middle
      cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed
      the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05)
      and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in subcortex (difference not significant).
      Ischemic injury volume was reduced by 22% in the cortex (p < 0.05) and 17% in the
      subcortex (p < 0.05) after inhibition of polyamine oxidase by MDL 72527. There
      was an increase in tissue putrescine levels together with a decrease in spermine
      and spermidine levels at the ischemic site compared with the nonischemic site
      after ischemia-reperfusion injury. The increase in putrescine levels at the
      ischemic cortical and subcortical region was reduced by a mean of 45% with MDL
      72527 treatment. These results suggest that the polyamine interconversion pathway
      has an important role in the postischemic increase in putrescine levels and that
      blocking of this pathway can be neuroprotective against neuronal cell damage
      after temporary focal cerebral ischemia.

PMID- 9930752
TI  - Increased DNA oxidation and decreased levels of repair products in Alzheimer's
      disease ventricular CSF.
AB  - One of the leading etiologic hypotheses regarding Alzheimer's disease (AD) is the
      involvement of free radical-mediated oxidative stress in neuronal degeneration.
      Although several recent studies show an increase in levels of brain DNA oxidation
      in both aging and AD, there have been no studies of levels of markers of DNA
      oxidation in ventricular CSF. This is a study of levels of 8-hydroxy-2'
      deoxyguanosine (8-OHdG), the predominant marker of oxidative DNA damage, in
      intact DNA and as the "free" repair product that results from repair mechanisms.
      Free 8-OHdG was isolated from CSF from nine AD and five age-matched control
      subjects using solid-phase extraction columns and measured using gas
      chromatography/mass spectrometry with selective ion monitoring. Intact DNA was
      isolated from the same samples and the levels of 8-OHdG determined in the intact
      structures. Quantification of results was carried out using stable isotope
      labeled 8-OHdG. By using this sensitive methodology, statistically significant
      elevations (p < 0.05) of 8-OHdG were observed in intact DNA in AD subjects
      compared with age-matched control subjects. In contrast, levels of free 8-OHdG,
      removed via repair mechanisms, were depleted significantly in AD samples (p <
      0.05). Our results demonstrate an increase in unrepaired oxygen radical-mediated
      damage in AD DNA as evidenced by the increased presence of 8-OHdG in intact DNA
      and decreased concentrations of the free repair product. These data suggest that
      the brain in AD may be subject to the double insult of increased oxidative
      stress, as well as deficiencies in repair mechanisms responsible for removal of
      oxidized bases.

PMID- 9930753
TI  - Effects of pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)
      on methamphetamine pharmacokinetics and striatal dopamine losses.
AB  - We recently demonstrated that pretreatment with N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4) exacerbates experimental parkinsonism induced by
      methamphetamine. The mechanism responsible for this effect remains to be
      elucidated. In this study, we investigated whether the exacerbation of chronic
      dopamine loss in DSP-4-pretreated animals is due to an impairment in the recovery
      of dopamine levels once the neurotoxic insult is generated or to an increased
      efficacy of the effects induced by methamphetamine. We administered different
      doses of methamphetamine either to DSP-4-pretreated or to intact Swiss-Webster
      mice and evaluated the methamphetamine-induced striatal dopamine loss at early
      and prolonged intervals. As a further step, we evaluated the striatal
      pharmacokinetics of methamphetamine, together with its early biochemical effects.
      We found that previous damage to norepinephrine terminals produced by DSP-4 did
      not modify the recovery of striatal dopamine levels occurring during several
      weeks after methamphetamine. By contrast, pretreatment with DSP-4 exacerbated
      early biochemical effects of methamphetamine, which were already detectable 1 h
      after methamphetamine administration. In addition, in norepinephrine-depleted
      animals, the clearance of striatal methamphetamine is prolonged, although the
      striatal concentration peak observed at 1 h is unmodified. These findings,
      together with the lack of a methamphetamine enhancement when DSP-4 was injected
      12 h after methamphetamine administration, suggest that in norepinephrine
      depleted animals, a more pronounced acute neuronal sensitivity to methamphetamine
      occurs.

PMID- 9930754
TI  - Extracellular glucose concentrations in the rat hippocampus measured by zero-net
      flux: effects of microdialysis flow rate, strain, and age.
AB  - The concentration of glucose in the brain's extracellular fluid remains
      controversial, with recent estimates and measurements ranging from 0.35 to 3.3
      mM. In the present experiments, we used the method of zeronet-flux microdialysis
      to determine glucose concentration in the hippocampal extracellular fluid of
      awake, freely moving rats. In addition, the point of zero-net-flux was measured
      across variations in flow rate to confirm that the results for glucose
      measurement were robust to such variations. In 3-month-old male Sprague-Dawley
      rats, the concentration of glucose in the hippocampal extracellular fluid was
      found to be 1.00 +/- 0.05 mM, which did not vary with changes in flow rate. Three
      month-old and 24-month-old Fischer-344 rats both showed a significantly higher
      hippocampal extracellular fluid glucose concentration, at 1.24 +/- 0.07 and 1.21
      +/- 0.04 mM, respectively; there was no significant difference between the two
      age groups. The present data demonstrate variation in extracellular brain glucose
      concentration between rat strains. When taken together with previous data showing
      a striatal extracellular glucose concentration on the order of 0.5 mM, the data
      also demonstrate variation in extracellular glucose between brain regions.
      Traditional models of brain glucose transport and distribution, in which
      extracellular concentration is assumed to be constant, may require revision.

PMID- 9930755
TI  - Structure and functional characterization of a novel human low-voltage activated
      calcium channel.
AB  - We have isolated and characterized overlapping cDNAs encoding a novel, voltage
      gated Ca2+ channel alpha1 subunit, alpha1H, from a human medullary thyroid
      carcinoma cell line. The alpha1H subunit is structurally similar to previously
      described alpha1 subunits. Northern blot analysis indicates that alpha1H mRNA is
      expressed throughout the brain, primarily in the amygdala, caudate nucleus, and
      putamen, as well as in several nonneuronal tissues, with relatively high levels
      in the liver, kidney, and heart. Ba2+ currents recorded from human embryonic
      kidney 293 cells transiently expressing alpha1H activated at relatively
      hyperpolarized potentials (-50 mV), rapidly inactivated (tau = 17 ms), and slowly
      deactivated. Similar results were observed in Xenopus oocytes expressing alpha1H.
      Single-channel measurements in human embryonic kidney 293 cells revealed a single
      channel conductance of approximately 9 pS. These channels are blocked by Ni2+
      (IC50 = 6.6 microM) and the T-type channel antagonists mibefradil (approximately
      50% block at 1 microM) and amiloride (IC50 = 167 microM). Thus, alpha1H
      containing channels exhibit biophysical and pharmacological properties
      characteristic of low voltage-activated, or T-type, Ca2+ channels.

PMID- 9930756
TI  - Calcium channels in the GABAergic presynaptic nerve terminals projecting to
      meynert neurons of the rat.
AB  - Effects of selective Ca2+ channel blockers on GABAergic inhibitory postsynaptic
      currents (IPSCs) were studied in the acutely dissociated rat nucleus basalis of
      Meynert (nBM) neurons attached with nerve endings, namely, the "synaptic bouton"
      preparation, and in the thin slices of nBM, using nystatin perforated and
      conventional whole-cell patch recording modes, respectively. In the synaptic
      bouton preparation, nicardipine (3 x 10(-6) M) and omega-conotoxin-MVIIC (3 x 10(
      6) M) reduced the frequency of spontaneous postsynaptic currents by 37 and 22%,
      respectively, whereas omega-conotoxin-GVIA had no effect. After blockade of L-
      and P/Q-type Ca2+ channels, successive removal of Ca2+ from external solution had
      no significant effect on the residual spontaneous activities, indicating that N-,
      R-, and T-type Ca2+ channels are not involved in the spontaneous GABA release.
      Thapsigargin, but not ryanodine, increased the frequency of spontaneous IPSCs in
      both the synaptic bouton and slice preparations, suggesting the partial
      contribution of the intracellular Ca2+ storage site to the spontaneous GABA
      release. In contrast, omega-conotoxin-GVIA (3 x 10(-6) M) and omega-conotoxin
      MVIIC (3 x 10(-6) M) suppressed the evoked IPSCs by 31 and 37%, respectively, but
      nicardipine produced no significant effect. The residual evoked currents were
      abolished in Ca2+-free external solution but not in the external solution
      containing 10(-5) M Ni2+, suggesting the involvement of N-, P/Q-, and R-type Ca2+
      channels but not L- and T-type ones in the evoked IPSCs. Neither thapsigargin nor
      ryanodine had any significant effects on the evoked IPSCs. It was concluded that
      Ca2+ channel subtypes responsible for spontaneous transmitter release are
      different from those mediating the transmitter release evoked by nerve
      stimulation.

PMID- 9930757
TI  - Suppression of the nicotinic acetylcholine response in rat superior cervical
      ganglionic neurons by steroids.
AB  - The effects of various types of steroids on the nicotinic acetylcholine (ACh)
      receptor (nAChR)-mediated responses were investigated in superior cervical
      ganglionic neurons acutely dissociated from rats using nystatin perforated patch
      recording. ACh induced a peak followed by a gradual decrease in the inward
      current at a holding potential of -40 mV. Nicotine, but not muscarine, mimicked
      ACh. Hydrocortisone at a concentration of >10(-6) M reversibly suppressed both
      the peak and steady-state nicotine-induced currents (Inic) in a noncompetitive
      manner. The inhibition of Inic by hydrocortisone did not show any voltage
      dependency and persisted in the presence of either cyclic AMP modulators,
      forskolin and 3-isobutyl-1-methylxanthine, or a protein kinase A inhibitor, N-[2
      (methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89). Beta
      estradiol, androsterone, aldosterone, and 17alpha-estradiol mimicked
      hydrocortisone in its inhibitory action on ACh-induced currents (I(ACh)). The
      potency for the inhibitory actions on I(ACh) was as follows: androsterone > beta
      estradiol > hydrocortisone > or = aldosterone = 17alpha-estradiol. Cholesterol
      had no effect on the I(ACh). In conclusion, the structural characteristics of a
      steroid are thus considered to be necessary to block nicotinic I(ACh) in rat
      superior cervical ganglionic cells, whereas the cholesterol side chain might
      disturb the inhibitory action of the steroid skeleton on nAChRs.

PMID- 9930758
TI  - Nuclear localization of the delta subunit of Ca2+/calmodulin-dependent protein
      kinase II in rat cerebellar granule cells.
AB  - To examine the physiological roles of the delta subunit of Ca2+/calmodulin
      dependent protein kinase II (CaM kinase IIdelta) in brain, we examined the
      localization of CaM kinase IIdelta in the rat brain. A specific antibody to CaM
      kinase IIdelta1-delta4 isoforms was prepared by immunizing rabbits with a
      synthesized peptide corresponding to the unique carboxyl-terminal end of these
      isoforms. The prepared antibody did not recognize the alpha, beta, and gamma
      subunits, which were each overexpressed in NG108-15 cells. Immunoblot analysis on
      various regions and the nuclear fractions from rat brains suggested that some
      isoforms of CaM kinase IIdelta1-delta4 were abundant in the nucleus in the
      cerebellum. Total RNA from the cerebellum was analyzed by RT-PCR with a primer
      pair from variable domain 1 to variable domain 2. We detected the three PCR
      products delta3.1, delta3.4, and delta3 that contained the nuclear localization
      signal. These CaM kinase IIdelta3 isoforms were localized in the nuclei in
      transfected NG108-15 cells. Immunohistochemical study suggested the existence of
      these isoforms in the nuclei in cerebellar granule cells. These results suggest
      that CaM kinase IIdelta3 isoforms are involved in nuclear Ca2+ signaling in
      cerebellar granule cells.

PMID- 9930759
TI  - An ecto-nucleotide pyrophosphatase is one of the main enzymes involved in the
      extracellular metabolism of ATP in rat C6 glioma.
AB  - The presence of a nucleotide pyrophosphatase (EC 3.6.1.9) on the plasma membrane
      of rat C6 glioma has been demonstrated by analysis of the hydrolysis of ATP
      labeled in the base and in the alpha- and gamma-phosphates. The enzyme degraded
      ATP into AMP and PPi and, depending on the ATP concentration, accounted for
      approximately 50-75% of the extracellular degradation of ATP. The association of
      the enzyme with the plasma membrane was confirmed by ATP hydrolysis in the
      presence of a varying concentration of pyridoxal phosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS), a membrane-impermeable inhibitor of the enzyme. PPADS
      concentration above 20 microM abolished the degradation of ATP into AMP and PPi.
      The nucleotide pyrophosphatase has an alkaline pH optimum and a Km for ATP of 17
      +/- 5 microM. The enzyme has a broad substrate specificity and hydrolyzes
      nucleoside triphosphates, nucleoside diphosphates, dinucleoside polyphosphates,
      and nucleoside monophosphate esters but is inhibited by nucleoside
      monophosphates, adenosine 3',5'-bisphosphate, and PPADS. The substrate
      specificity characterizes the enzyme as a nucleotide
      pyrophosphatase/phosphodiesterase I (PD-I). Immunoblotting and autoadenylylation
      identified the enzyme as a plasma cell differentiation antigen-related protein.
      Hydrolysis of ATP terminates the autophosphorylation of a nucleoside diphosphate
      kinase (NDPK/nm23) detected in the conditioned medium of C6 cultures. A function
      of the pyrophosphatase/PD-I and NDPK in the purinergic and pyrimidinergic signal
      transduction in C6 is discussed.

PMID- 9930760
TI  - Contribution of metabotropic glutamate receptor mGluR4 to L-2-[3H]amino-4
      phosphonobutyrate binding in mouse brain.
AB  - The binding of L-2-[3H]amino-4-phosphonobutyrate ([3H]L-AP4) was examined in
      brain sections of wild-type mice and mice lacking the mGluR4 subtype of
      metabotropic glutamate receptors (mGluRs). Very high relative densities of [3H]L
      AP4 binding were observed in the molecular layer of the cerebellar cortex, the
      nucleus basalis, the outer layer of the superior colliculus, and the substantia
      nigra. In mGluR4 knock-out mice, very low levels of binding were observed in
      these regions. The moderate levels of binding observed with wild-type mice in the
      molecular layer of the hippocampal dentate gyrus and in the thalamus were absent
      in mGluR4 knock-out mice. In contrast, the moderate levels observed in most of
      the cerebral cortex, caudate putamen, and globus pallidus were not different in
      mGluR4 knock-out mice compared with wild-type. In these regions, mGluR8 is likely
      to be labeled by [3H]L-AP4 because mGluR8 is expressed in such brain regions and,
      like mGluR4, has high affinity for L-AP4. We conclude that mGluR4 contributes
      substantially to the high-affinity binding site for [3H]L-AP4 in several regions
      of mouse brain, including cerebellar cortex, nucleus basalis, thalamus, superior
      colliculus, substantia nigra, and hippocampal dentate gyrus.

PMID- 9930761
TI  - Light-induced variations in AP-1 binding activity and composition in the rat
      suprachiasmatic nucleus.
AB  - Expression of immediate early genes, including fos-like and jun-like genes, in
      the suprachiasmatic nucleus is believed to be part of the mechanism for photic
      entrainment of circadian rhythms to the environmental light/dark cycle. However,
      the effects of a light stimulus on activating protein-1 (AP-1) complexes in the
      suprachiasmatic nucleus remain unclear. The photic regulation of AP-1 DNA-binding
      activity and composition in the rat suprachiasmatic nucleus was evaluated by
      using an electrophoretic mobility shift assay. A light pulse given during
      subjective night induced an increase in AP-1 binding activity when either nuclear
      or whole-cell extracts from suprachiasmatic nuclei were used. Under constant dark
      conditions, proteins that are predominant components of AP-1 complexes are Fra-2
      and Jun-D. Under light stimulation, c-Fos and Jun-B consistently increased, as
      expected, but this was also the case for Fra-2, Jun-D, and c-Jun, although to a
      lesser extent. An immunocytochemical study of the Fra-2 expression pattern
      demonstrated the presence of the protein in the ventrolateral as well as in the
      dorsomedial subdivisions of the suprachiasmatic nucleus. Light regulation of Fra
      2 immunoreactivity, however, appeared to be restricted to the ventrolateral
      subdivision. It is concluded that light may be acting both by increasing
      constitutive AP-1 complexes and by inducing the expression of specific complexes.

PMID- 9930762
TI  - Immunocytochemical localization and biological activity of hydroxysteroid
      sulfotransferase in the frog brain.
AB  - Biosynthesis of the neuroactive steroids pregnenolone sulfate (delta5PS) and
      dehydroepiandrosterone sulfate (DHEAS) is catalyzed by the enzyme hydroxysteroid
      sulfotransferase (HST), which transfers the sulfonate moiety from 3'
      phosphoadenosine 5'-phosphosulfate (PAPS) on the 3-hydroxy site of steroids.
      Although high concentrations of delta5PS and DHEAS have been detected in the rat
      brain, the anatomical localization of HST in the CNS has never been determined.
      Using an antiserum against rat liver HST, we have investigated the distribution
      of HST-like immunoreactivity in the CNS of the frog Rana ridibunda. Two
      populations of HST-immunoreactive neurons were observed in the hypothalamus, and
      several bundles of positive nerve fibers were visualized in the telencephalon and
      diencephalon. Incubation of frog brain homogenates with [35S]PAPS and
      [3H]pregnenolone yielded the formation of several 3H,35S-labeled compounds,
      including delta5PS and testosterone sulfate. When [3H]dehydroepiandrosterone and
      [35S]PAPS were used as precursors, one of the 3H,35S-labeled metabolites coeluted
      with DHEAS. Neosynthesis of [3H]delta5PS and [3H]DHEAS was reduced significantly
      by 2,4-dichloro-6-nitrophenol, a specific inhibitor of sulfotransferases. The
      present study provides the first immunocytochemical mapping of HST in the brain.
      Our data also demonstrate for the first time that biosynthesis of the highly
      potent neuroactive steroids delta5PS and DHEAS occurs in the CNS of nonmammalian
      vertebrates.

PMID- 9930763
TI  - Effects of peripheral axotomy on cholecystokinin neurotransmission in the rat
      spinal cord.
AB  - Because cholecystokinin (CCK) acts as a "functional" endogenous opioid
      antagonist, it has been proposed that changes in central CCKergic
      neurotransmission might account for the relative resistance of neuropathic pain
      to the analgesic action of morphine. This hypothesis was addressed by measuring
      CCK-related parameters 2 weeks after unilateral sciatic nerve section in rats. As
      expected, significant decreases (-25-38%) in the tissue concentrations and in
      vitro release of both substance P and calcitonin gene-related peptide were noted
      in the dorsal quadrant of the lumbar spinal cord on the lesioned side. In
      contrast, the tissue levels and in vitro release of CCK were unchanged in the
      same area in lesioned rats. Measurements in dorsal root ganglia at L4-L6 levels
      revealed no significant changes in proCCK mRNA after the lesion. However, sciatic
      nerve section was associated with a marked ipsilateral increase in both CCK-B
      receptor mRNA levels in these ganglia (+70%) and the autoradiographic labeling of
      CCK-B receptors by [3H]pBC 264 (+160%) in the superficial layers of the lumbar
      dorsal horn. Up-regulation of CCK-B receptors rather than CCK synthesis and
      release probably contributes to increased spinal CCKergic neurotransmission in
      neuropathic pain.

PMID- 9930764
TI  - Characterization and distribution of ferritin binding sites in the adult mouse
      brain.
AB  - Studies on iron uptake into the brain have traditionally focused on transport by
      transferrin. However, transferrin receptors are not found in all brain regions
      and are especially low in white matter tracts where high iron concentrations have
      been reported. Several lines of research suggest that a receptor for ferritin,
      the intracellular storage protein for iron, may exist. We present, herein,
      evidence for ferritin binding sites in the brains of adult mice. Autoradiographic
      studies using 125I-recombinant human ferritin demonstrate that ferritin binding
      sites in brain are predominantly in white matter. Saturation binding analyses
      revealed a single class of binding sites with a dissociation constant (K(D)) of
      4.65 x 10(-9) M and a binding site density (Bmax of 17.9 fmol bound/microg of
      protein. Binding of radiolabeled ferritin can be competitively displaced by an
      excess of ferritin but not transferrin. Ferritin has previously been shown to
      affect cellular proliferation, protect cells from oxidative damage, and deliver
      iron. The significance of a cellular ferritin receptor is that ferritin is
      capable of delivering 2,000 times more iron per mole of protein than transferrin.
      The distribution of ferritin binding sites in brain vis-a-vis transferrin
      receptor distribution suggests distinct methods for iron delivery between gray
      and white matter.

PMID- 9930766
TI  - The mood-stabilizing agents lithium and valproate robustly increase the levels of
      the neuroprotective protein bcl-2 in the CNS.
AB  - Differential display of mRNA was used to identify concordant changes in gene
      expression induced by two mood-stabilizing agents, lithium and valproate (VPA).
      Both treatments, on chronic administration, increased mRNA levels of the
      transcription factor polyomavirus enhancer-binding protein (PEBP) 2beta in
      frontal cortex (FCx). Both treatments also increased the DNA binding activity of
      PEBP2 alphabeta and robustly increased the levels of bcl-2 (known to be
      transcriptionally regulated by PEBP2) in FCx. Immunohistochemical studies
      revealed a marked increase in the number of bcl-2-immunoreactive cells in layers
      2 and 3 of FCx. These novel findings represent the first report of medication
      induced increases in CNS bcl-2 levels and may have implications not only for mood
      disorders, but also for long-term treatment of various neurodegenerative
      disorders.

PMID- 9930765
TI  - In vitro evidence for increased facilitation of striatal acetylcholine release
      via pre- and postsynaptic NMDA receptors in hemiparkinsonian rats.
AB  - The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was
      investigated in rats subjected to unilateral injection of 6-hydroxydopamine into
      the substantia nigra. In slices prepared from the striatum contralateral to the
      lesion, the NMDA-evoked endogenous acetylcholine release was not significant at
      10 microM NMDA and maximal at 100 microM NMDA (124 +/- 19%). Conversely, in
      slices taken from the dopamine-depleted striatum, NMDA was effective even at 10
      microM (41 +/- 4%), and at 100 microM (196 +/- 24%) efficacy was nearly doubled.
      In synaptosomes prepared from the contralateral striatum, NMDA maximally
      stimulated 20 mM KCl-induced endogenous acetylcholine release at 1 microM (66 +/-
      5.1%), with lower concentrations (0.01-0.1 microM) being ineffective. Conversely,
      in synaptosomes prepared from the dopamine-depleted striatum, NMDA maximally
      enhanced the K+/--evoked acetylcholine release at 0.1 microM (118 +/- 12.4%).
      Concentration-response curves of NMDA-evoked acetylcholine release in sham
      operated rats could be superimposed on those observed in the contralateral
      striatum of the 6-hydroxydopamine-lesioned animals. The present data support the
      view of an increased glutamatergic regulation of striatal acetylcholine release
      via pre- and postsynaptic NMDA receptors during Parkinson's disease.

PMID- 9930767
TI  - Serotonin 5-HT7 receptors binding to rat hypothalamic membranes.

PMID- 9930768
TI  - Occult is a matter of definition.

PMID- 9930769
TI  - Liability of radiologists when supervising technologists.

PMID- 9930770
TI  - Eugene W. Caldwell Lecture. Pediatric imaging: the oldest radiological
      subspecialty comes of age.

PMID- 9930771
TI  - Computerized realistic simulation: a teaching module for crisis management in
      radiology.
AB  - OBJECTIVE: Computerized realistic simulation technology has been used as a
      training tool in fields such as aviation and military training and in the nuclear
      power industry. More recently, it has been adapted for use in anesthesia crisis
      resource management. We describe the effectiveness of a simulation program like
      that used by anesthesiology departments that we developed to teach radiologists
      the principles of crisis management. MATERIALS AND METHODS: A mock CT scanner and
      patient simulator were used to simulate the environment in which radiologists
      encounter crises. Twenty-four residents attended the training program, four at
      each half-day session. Two responded to and two observed an initial crisis, after
      which they attended a lecture and watched a videotape review. The second pair
      then participated in a different crisis scenario. The scenario order was
      randomized. All scenarios were videotaped and randomly reviewed by two physicians
      not involved with the course. The following behavioral qualities of the
      participating residents were evaluated using a five-point scale, ranging from
      poor (1) to excellent (5): global assessment, communication skills, use of
      support personnel, use of resources, and role clarity. Residents then rated the
      course on a five-point scale using the following criteria: overall course
      usefulness, attainment of course goals, realism of scenarios, quality of lecture,
      and quality of videotape review. RESULTS: The trainees who had attended the
      lecture and watched the videotape review before participating in a scenario
      consistently scored higher than those who had not in the following areas (score
      after training/score before training): global assessment, 4.08/2.50;
      communication skills, 4.09/2.67; use of support personnel, 4.17/3.00; use of
      resources, 4.00/2.92; and role clarity, 4.17/2.67. Moreover, the participants
      gave the course the following average ratings: overall usefulness, 4.93;
      attainment of course goals, 4.78; realism of scenarios, 4.63; quality of lecture,
      4.63; and quality of videotape review, 4.85. CONCLUSION: Although the critical
      assessment of a teaching method is difficult and subjective by nature, the
      improvement in behavioral performance scores suggests that simulation technology
      effectively conveyed the principles of crisis management. The course ratings show
      that the program was well accepted by participants.

PMID- 9930772
TI  - Viewing DICOM-compliant CT images on a desktop personal computer: use of an
      inexpensive DICOM receive agent and freeware image display applications.
AB  - OBJECTIVE: Our objective was to determine the ease of installation and use of
      relatively inexpensive and free software applications that allow Macintosh users
      to receive and view CT images from a Digital Imaging and COmmunication in
      Medicine-compliant imaging network. CONCLUSION: Simple-to-use Macintosh-based
      options to transfer and view images are readily available and easily installed by
      users with minimal computer expertise.

PMID- 9930773
TI  - Ability of mammography to reveal nonpalpable breast cancer in women with palpable
      breast masses.
AB  - OBJECTIVE: Our goal was to determine the frequency with which mammography reveals
      nonpalpable malignancies in women with benign palpable masses and to compare
      these nonpalpable malignancies with the palpable malignancies and nonpalpable
      malignancies detected in asymptomatic women. SUBJECTS AND METHODS: This study of
      nominally asymptomatic women involved 85,399 consecutive mammographic
      examinations, of which 3459 (4.1%) examinations were performed on women who had
      palpable masses identified before or at the time of mammography. A medical
      outcomes audit identified mammographic examinations after which breast cancer was
      diagnosed and determined selected surrogate measures for mortality reduction for
      the mammographically detected malignancies. RESULTS: Of the 3459 examinations in
      women with palpable masses, 64 cases of cancer were revealed by mammography. Of
      these, 54 cases involved palpable malignancies (15.6/1000 examinations) and 10
      involved nonpalpable malignancies (2.6/1000 examinations). Of the 81,940
      examinations in asymptomatic women, 346 cases of nonpalpable cancer were detected
      (4.2/1000 examinations). Of the 10 cases of nonpalpable cancer detected in women
      with benign palpable masses, median tumor size was 13.8 mm, 10% had axillary node
      metastasis, and 10% were stage 2 or higher. The corresponding surrogate measures
      for cases of nonpalpable cancer detected in asymptomatic women were median tumor
      size, 13.6 mm; node metastasis, 7%; stage 2 or higher, 14%. The surrogate
      measures for the 54 palpable malignancies were median tumor size, 23.7 mm; node
      metastasis, 31%; stage 2 or higher, 63%. CONCLUSION: The surrogate measures for
      the nonpalpable malignancies in women with benign palpable lesions resemble those
      in asymptomatic women and are much more favorable than those of palpable
      malignancies. Therefore, in women with a palpable breast mass, it is important to
      use mammography to screen the remainder of both breasts for nonpalpable cancer.

PMID- 9930774
TI  - Relationship between mammographic screening intervals and size and histology of
      ductal carcinoma in situ.
AB  - OBJECTIVE: The objective of this study was to determine how the length of time
      between mammographic screenings is related to the size, grade, and histology of
      mammographically detected ductal carcinoma in situ (DCIS). MATERIALS AND METHODS:
      We retrospectively reviewed 166 consecutive mammograms of women evaluated for
      DCIS with (n = 24) and without (n = 142) microinvasion. The size of the DCIS was
      determined by the maximum diameter as measured on the mammogram. After pathologic
      analysis, DCIS was classified by histologic architecture, nuclear grade, presence
      of microinvasion, and presence of multifocality. Four screening intervals were
      defined: annual (6-17 months), biennial (18-29 months), triennial (> or = 30
      months), and first time. Patients were grouped according to screening intervals.
      The average age of all groups was 55 years. RESULTS: The annual group (mean size
      of DCIS, 1.69 cm) had significantly smaller DCIS than did the biennial (mean
      size, 2.27 cm), triennial (mean size, 3.49 cm), or first time groups (mean size,
      3.29 cm) (p = .003). Comedo histology was more frequently observed in patients
      screened biennially (73.7%) than in those screened annually (46.8%) (p = .05).
      High-grade nuclear histology was more commonly seen in the biennial (76.3%) than
      in the annual (48.1%) screening group (p = .008). We found no significant
      correlation between screening interval and the incidence of microinvasion and
      multifocality. CONCLUSION: Small, low-grade noncomedo DCIS was more common in the
      annual mammographic screening group than in the biennial screening group. A
      direct relationship was found between DCIS size and length of screening interval:
      DCIS detected at annual screening was smaller than that found at biennial
      screening, which in turn was smaller than DCIS revealed at triennial screening.
      This study provides inferential support for annual screening mammography for DCIS
      detection and management.

PMID- 9930775
TI  - Tubular carcinoma of the breast: sensitivity of diagnostic techniques and
      correlation with histopathology.
AB  - OBJECTIVE: Our objective was to assess our experience in diagnosing pure tubular
      carcinoma of the breast and to correlate the radiologic and histopathologic
      features. MATERIALS AND METHODS: A retrospective review of 932 consecutive cases
      of proven breast cancer diagnosed between 1990 and 1997 revealed 78 cases (8.4%)
      of tubular carcinoma in 69 patients. Clinical, imaging, cytologic, and histologic
      findings were analyzed. RESULTS: Mammography revealed tubular carcinoma in 68
      (87%) of the 78 cases. Sonography showed tubular carcinoma in all 38 cases in
      which it was used; nine of these lesions were mammographically occult. These nine
      lesions were slightly, but not significantly (p < .05), smaller than the 29
      lesions that had also been detected on mammography. Large core needle biopsy was
      performed in 22 patients (sensitivity, 91%). At biopsy, diagnoses were malignant
      (n = 16 [73%]), suspicious (n = 4 [18%]), atypia (n = 1 [4.5%]), and benign (n =
      1 [4.5%]). Fine-needle aspiration biopsy was used to evaluate 36 cases of tubular
      carcinoma (sensitivity, 50%); cytologic diagnoses were malignant (n = 15 [42%]),
      suspicious (n = 3 [8%]), atypia (n = 10 [28%]), and benign (n = 8 [22%]). Only 15
      (19%) of the 78 tubular carcinomas were palpable. Other tumors were detected
      within the excised tissue in 47 of the patients (68%); of these other types of
      lesions, ductal carcinoma in situ was found most often. CONCLUSION: Most cases of
      tubular carcinoma can be revealed by mammography; for mammographically occult
      tubular carcinoma, sonography can be performed. The rate of accuracy for
      determining the presence of tubular carcinoma is higher with large core needle
      biopsy than with fine-needle aspiration biopsy. Finally, when tubular carcinoma
      is diagnosed, other histologic types of carcinoma often occur in the same breast.

PMID- 9930776
TI  - Sonographic evaluation of infiltrating lobular carcinoma.
AB  - OBJECTIVE: Infiltrating lobular carcinoma (ILC), which accounts for 7-10% of all
      breast malignancies, often poses diagnostic difficulties. The purpose of our
      study was to correlate the clinical, mammographic, and sonographic findings in
      each histologic subtype of ILC and to evaluate the sensitivity of sonography in
      its diagnosis. MATERIALS AND METHODS: We reviewed 208 cases of invasive lobular
      carcinoma. In 81 of these tumors, sonography was performed to further examine a
      mammographically invisible palpable abnormality or a mammographically subtle
      lesion. A dedicated breast pathologist classified each of these tumors as pure
      invasive lobular carcinoma or mixed invasive lobular and ductal carcinoma. Pure
      ILC tumors were further subclassified as one of five histologic subtypes. We
      retrospectively studied the clinical, mammographic, and sonographic findings in
      each histologic tumor subtype. RESULTS: The most common sonographic appearance of
      ILC was a heterogeneous, hypoechoic mass with angular or ill-defined margins and
      posterior acoustic shadowing, which was seen in 60.5% (49/81) of tumors. Of the
      remaining 32 tumors, 15% (12/81) showed focal shadowing without a discrete mass,
      12% (10/81) appeared as a lobulated, well-circumscribed mass, and 12% (10/81)
      were sonographically invisible. Although considerable overlap occurred among
      histologic subtypes, classic ILC tended to present as focal shadowing without a
      discrete mass; pleomorphic ILC typically was seen as a shadowing mass; and, of
      all the tumor subtypes, signet, alveolar, and solid ILC were most likely to be
      revealed on sonography as a lobulated, well-circumscribed mass. In the 81
      mammographically subtle or invisible lesions, sonography detected the tumor in
      87.7% (71/81). The sensitivity of sonography in tumors smaller than 1 cm was
      85.7% (12/14). CONCLUSION: High-resolution sonography of the breast is a useful
      adjunct in the evaluation of ILC, a neoplasm that frequently presents a clinical
      and mammographic diagnostic challenge.

PMID- 9930777
TI  - Percutaneous large-core biopsy of papillary breast lesions.
AB  - OBJECTIVE: This study was undertaken to assess the accuracy of percutaneous large
      core biopsy in evaluating papillary breast lesions. MATERIALS AND METHODS: A
      retrospective review of imaging-guided large-core breast biopsy of 1077
      consecutive lesions revealed that papillary lesions were diagnosed in 34 (3%)
      cases. Surgical correlation (n = 22) or minimum 2 years' mammographic follow-up
      (n = 4) were available for 26 papillary lesions. Mammographic and histologic
      findings in these 26 cases were reviewed. RESULTS: Percutaneous biopsy histology
      had benign findings in nine lesions, atypical in 10, and malignant in seven. Of
      seven lesions yielding benign papilloma at percutaneous biopsy, none (0%) had
      carcinoma at surgery or mammographic follow-up. Surgery revealed carcinoma in one
      of two lesions yielding papillomatosis at percutaneous biopsy. This lesion was a
      spiculated mass; surgical biopsy, recommended because of mammographic-histologic
      discordance, revealed a radial sclerosing lesion and ductal carcinoma in situ
      (DCIS). Of 10 papillary lesions with atypical ductal hyperplasia at percutaneous
      biopsy, surgery revealed DCIS in three (30%). Of seven lesions in which
      percutaneous biopsy yielded papillary DCIS, surgery revealed DCIS in all seven;
      three (43%) also had invasive carcinoma. CONCLUSION: Among our patients,
      diagnosis by percutaneous core biopsy of benign papillary lesions proved to be
      accurate when concordant with imaging findings. Surgical excision was indicated
      when diagnosis by percutaneous biopsy revealed atypical papillary lesions or
      papillary DCIS. A larger series with longer follow-up is required to assess the
      clinical course of benign papillary lesions without atypia that are not excised
      after percutaneous large-core breast biopsy.

PMID- 9930778
TI  - Coding mammograms using the classification "probably benign finding--short
      interval follow-up suggested".
AB  - OBJECTIVE: Many benign breast lesions revealed by mammography show features
      indicating that the lesions have a high, but not complete, likelihood of being
      benign. The Breast Imaging Reporting and Data System (BI-RADS) allows
      radiologists to classify these mammograms as "probably benign finding-short
      interval follow-up suggested" (category 3). We explored whether certain factors
      are associated with the use of category 3 in a national cancer detection program.
      MATERIALS AND METHODS: We analyzed data from the National Breast and Cervical
      Cancer Early Detection Program, a comprehensive nationwide program that provides
      cancer screening for low-income and medically underserved women. The study
      population included all women at least 40 years old who had undergone mammography
      on or before September 30, 1996 (n = 372,760). RESULTS: Of the 372,760
      mammograms, 7.7% were classified as category 3. The probability of receiving a
      category 3 classification decreased as patients' ages increased. Women who were
      symptomatic were nearly twice as likely as women who were asymptomatic to receive
      a category 3 classification, and women whose clinical breast examinations had
      abnormal findings were more than twice as likely as women with examinations
      having normal findings to receive a category 3 classification. The percentage of
      mammograms classified as category 3 by state or tribal organization ranged from
      1.4% to 14.0%. CONCLUSION: Several patient variables, including patient
      symptomatology, were associated with the probability of having a mammogram
      classified as category 3. One of the most important determinants was where the
      patient underwent mammography, which suggests that variability exists among
      radiologists themselves in using this BI-RADS code for "probably benign"
      mammographic lesions.

PMID- 9930779
TI  - Sonography of nonmammary malignancies of the breast.

PMID- 9930780
TI  - Cowden disease: a cutaneous marker for increased risk of breast cancer.

PMID- 9930781
TI  - Helical CT of pulmonary nodules in patients with extrathoracic malignancy: CT
      surgical correlation.
AB  - OBJECTIVE: Our aim was to assess the sensitivity of helical CT for revealing
      pulmonary nodules. Thoracotomy with palpation of the deflated lung, resection,
      and histologic examination of palpable nodules was used as the gold standard.
      SUBJECTS AND METHODS: Thirteen patients underwent helical CT (slice thickness, 5
      mm; reconstruction intervals, 3 mm and 5 mm; interpreted by two independent
      observers). Subsequently, patients underwent unilateral (n = 6) or bilateral (n =
      7) surgical exploration, and CT-surgical correlation of 20 lungs was performed.
      RESULTS: Ninety nodules were resected (61 were smaller than 6 mm; 13 were 6-10
      mm; 11 were larger than 10 mm; in five nodules, the size was not recorded at
      surgery). Sixty-nine nodules were located in the pulmonary parenchyma and 21 in
      the visceral pleura. Of the 90 lesions, 43 (48%) were found on histology to
      represent metastases. For lesions detected by at least one observer, the
      sensitivity of helical CT was 69% for intrapulmonary nodules smaller than 6 mm,
      95% for intrapulmonary nodules larger than or equal to 6 mm, and 100% for
      histologically proven intrapulmonary metastases larger than or equal to 6 mm. For
      lesions smaller than or equal to 10 mm, sensitivity was better using a
      reconstruction interval of 3 mm rather than of 5 mm. CONCLUSION: In this study,
      the sensitivity of helical CT exceeded the sensitivity of conventional CT in
      previous reports. However, because of limitations in the detection of
      intrapulmonary nodules smaller than 6 mm and of pleural lesions, complete
      surgical exploration should remain the procedure of choice in patients undergoing
      pulmonary metastasectomy. Preoperative helical CT should be used to guide the
      surgeon to lesions that are difficult to palpate.

PMID- 9930782
TI  - Pericardial thickening or effusion in patients with pulmonary artery
      hypertension: a CT study.
AB  - OBJECTIVE: The aim of the study was to determine the prevalence of pericardial
      thickening or effusion revealed by CT in patients with pulmonary artery
      hypertension. MATERIALS AND METHODS: Forty-five patients underwent pulmonary
      artery catheterization and CT of the thorax. On CT, we measured the maximum
      pericardial thickness, total pericardial score (the sum of four measures of
      pericardial thickness), and thickness of the anterior pericardial recess.
      Patients were grouped according to mean pulmonary artery pressure: group 1, less
      than 21 mm Hg (n = 15); group 2, 21-35 mm Hg (n = 15); and group 3, greater than
      35 mm Hg (n = 15). RESULTS: The prevalence of an increased pericardial score and
      increased maximum pericardial thickening was higher in group 3 than in group 1 or
      group 2 (p = .02 and < .001, respectively). Anterior pericardial recess
      thickening was markedly increased in group 3 (p < .0001). For all patients,
      significant correlations (Spearman's rank correlation coefficient = .44-.56, p <
      .005-.0001) were found between mean pulmonary artery pressure and all pericardial
      measures. CONCLUSION: On CT, pericardial thickening or effusion is a frequent
      finding in patients with severe pulmonary hypertension.

PMID- 9930783
TI  - Bronchopericardial fistula after placement of an automatic implantable
      cardioverter defibrillator: radiographic and CT findings.
AB  - OBJECTIVE: We describe our experience with bronchopericardial fistula as a
      complication of infection in patients who have undergone placement of automatic
      implantable cardioverter defibrillator systems. CONCLUSION: Bronchopericardial
      fistula should be suspected in patients who present with hemoptysis and who have
      undergone placement of an automatic implantable cardioverter defibrillator using
      pericardial or epicardial defibrillator patches. Air between a defibrillator
      patch and the heart on chest radiographs or CT is diagnostic.

PMID- 9930784
TI  - Mycetoma of the lung in a cavity that developed from a gunshot wound.

PMID- 9930785
TI  - Late tracheal compression complicating plombage.

PMID- 9930786
TI  - CT enteroclysis: a superfluous diagnostic procedure or valuable when
      investigating small-bowel disease?

PMID- 9930787
TI  - Comparison of two barium suspensions for dedicated small-bowel series.
AB  - OBJECTIVE: The in vivo radiographic features of two commercially available
      formulations of barium used as contrast media in dedicated small-bowel series
      were compared. SUBJECTS AND METHODS: Fifty-six consecutive outpatients referred
      for a dedicated small-bowel series were randomly administered either E-Z-Paque or
      Entrobar. Representative survey radiographs from each examination were randomized
      and reviewed by six gastrointestinal radiologists from three institutions. Each
      observer assigned a numeric score (1 = poor, 2 = fair, 3 = good, and 4 =
      excellent) that rated the quality of the radiograph with respect to these
      characteristics: definition of fold pattern, translucency, distention, and
      integrity of the barium column. Statistical analysis was performed for each
      characteristic using Wilcoxon's two-sample rank sum test. RESULTS: All six
      observers found a statistically significant difference between the two barium
      formulations for mean scores for definition of fold pattern and translucency.
      Mean scores for fold pattern were 3.3, 3.0, 3.2, 3.6, 3.3, and 3.4 for Entrobar
      and 2.1, 2.3, 2.4, 3.2, 2.6, and 2.7 for E-Z-Paque. Mean scores for translucency
      were 2.5, 2.7, 2.8, 3.1, 2.7, and 3.3 for Entrobar and 1.6, 1.7, 2.1, 2.3, 1.9,
      and 2.7 for E-Z-Paque. No statistically significant difference was found for mean
      score for distention or integrity of the barium column. CONCLUSION: On
      radiographs, Entrobar was found to have superior characteristics for
      visualization of fold pattern and translucency but offered no advantages for
      distention or integrity of the barium column. Improved translucency and
      definition of fold pattern may translate into improved sensitivity and confidence
      in diagnosing small-bowel abnormality.

PMID- 9930788
TI  - Local invasion of gastric cancer: CT findings and pathologic correlation using 5
      mm incremental scanning, hypotonia, and water filling.
AB  - OBJECTIVE: Our purpose was to assess the accuracy of CT with drug-induced
      hypotonia and water filling in revealing the depth of tumor invasion of the
      gastric wall, according to the T factor of TNM classification, and to verify the
      capability of this technique in differentiating diffuse from intestinal gastric
      cancer. SUBJECTS AND METHODS: Forty patients (age range, 35-78 years) with
      histologically proven gastric tumors underwent CT, in the prone position, with
      drug-induced hypotonia and water filling. The images were prospectively reviewed
      by two radiologists who were asked to assess the depth of tumor invasion in the
      gastric wall. The thickening of the hypodense layer and the contrast enhancement
      of lesion were measured. RESULTS: CT correctly assessed gastric wall invasion in
      77% and 82% of cases for observers A and B, respectively; overstaging was 20% and
      15%, respectively; and understaging occurred in 3% of cases for both observers.
      Diagnostic sensitivity for serosal invasion was 100% for both observers;
      specificity was 80% and 87%, respectively. Substantial agreement between the
      observers was obtained (kappa = .6). Diffuse and intestinal cancers could be
      differentiated by CT in 92% of cases, considering the thickening of the
      hypoattenuating layer of the gastric wall (diffuse cancer: 7 +/- 1.2 mm;
      intestinal cancer: 1.4 +/- 0.4 mm) and contrast enhancement (diffuse cancer: 85
      +/- 8.2 H; intestinal cancer: 51 +/- 3 H). CONCLUSION: CT with patients in a drug
      induced hypotonia and in a prone position, and using water filling, is a
      promising technique for evaluating the depth of tumor invasion and for
      differentiating intestinal from diffuse gastric cancer.

PMID- 9930789
TI  - CT findings after laparoscopic repair of ventral hernia.
AB  - OBJECTIVE: We describe CT findings after laparoscopic repair of ventral hernia
      with emphasis on formation of postoperative fluid collections that can mimic
      recurrent bowel herniation or infected postoperative fluid collections.
      CONCLUSION: The porous property of the mesh used in laparoscopic repair of
      ventral hernia allows reaccumulation of fluid in the existing hernia sac or
      spaces in the subcutaneous tissues that can be created by laparoscopic
      manipulation. These fluid collections should be expected and are differentiated
      from infected fluid collections or hernia recurrence by clinical presentation,
      laboratory data, and lack of ancillary features associated with true hernia such
      as presence of hernia sac, herniated mesentery, or bowel obstruction.

PMID- 9930790
TI  - Using CT to reveal fat-containing abnormalities of the pancreas.

PMID- 9930791
TI  - The cause of nontumorous defects of portal perfusion in the hepatic hilum
      revealed by CT during arterial portography.
AB  - OBJECTIVE: We investigated the cause of nontumorous defects of portal perfusion
      in the hepatic hilum revealed by CT during arterial portography (CTAP). MATERIALS
      AND METHODS: One hundred sixty patients who simultaneously underwent CTAP and CT
      during hepatic arteriography of the common hepatic artery formed the basis of our
      study. The frequency, site, and shape of nontumorous defects of portal perfusion
      in the hepatic hilum on CTAP and the findings on CT during hepatic arteriography
      were determined. In 13 patients in whom nontumorous portal perfusion defects were
      observed on CTAP, CT was performed during selective angiography via the gastric
      artery, pancreaticoduodenal artery, or both. RESULTS: Nontumorous defects of
      portal perfusion were detected in 49 regions in 33 of the 160 patients (dorsum of
      segment IV, n = 30; dorsum of the lateral segment, n = 11; segment I, n = 8). Of
      the 33 patients, 16 had two defects each. Of the 49 nontumorous defects of portal
      perfusion, 38 showed enhancement on CT during hepatic arteriography. In the 13
      patients who underwent CT during selective arteriography, enhancement due to
      nonportal venous inflow was seen in 16 of the 19 areas of decreased nontumorous
      portal perfusion (dorsum of segment IV, nine of 11; dorsum of the lateral
      segment, four of five; segment I, three of three). CONCLUSION: The main cause of
      nontumorous defects of portal perfusion in the hepatic hilum revealed by CTAP is
      decreased portal inflow due to nonportal supply via the parabiliary venous
      system. Thus, such lesions were also enhanced at a high frequency on CT during
      hepatic arteriography.

PMID- 9930793
TI  - Fat collection related to the intrahepatic inferior vena cava on CT.
AB  - OBJECTIVE: The purpose of our study is to describe the CT findings of fat
      collections related to the intrahepatic inferior vena cava and to review the
      literature about this benign incidental finding. CONCLUSION: Focal collections of
      fat related to the inferior vena cava are benign incidental findings located
      exclusively at the level of the liver. The fat collections are always adjacent to
      the medial wall of the inferior vena cava; appear to be extraluminal in origin
      and may, in fact, be entirely extraluminal; and are uncommon findings that are
      usually of no clinical significance.

PMID- 9930792
TI  - Proximal arterioportal shunting associated with hepatocellular carcinoma:
      features revealed by dynamic helical CT.
AB  - OBJECTIVE: This study investigated the findings revealed by dynamic helical CT of
      proximal arterioportal shunting associated with hepatocellular carcinoma. We also
      evaluated the diagnostic capability of this imaging technique to reveal the mass
      in patients with hepatocellular carcinoma. CONCLUSION: On dynamic helical CT,
      proximal arterioportal shunting altered liver perfusion and tumor enhancement.
      Heterogeneous enhancement of liver parenchyma and decreased enhancement of
      hepatomas diminished diagnostic capability on the arterial dominant phase image.
      However, with the addition of imaging in the arterial portal phase, lesion
      conspicuity improved.

PMID- 9930794
TI  - Gadolinium-enhanced three-dimensional MR portal venography.

PMID- 9930795
TI  - Spectrum of transient hepatic attenuation differences in biphasic helical CT.

PMID- 9930796
TI  - Seminomas complicating undescended intraabdominal testes in patients with prior
      negative findings from surgical exploration.
AB  - OBJECTIVE: This paper describes the clinical and imaging characteristics of
      seminoma complicating intraabdominal testes in three patients who had a history
      of negative findings from surgical exploration of the inguinal canal and scrotum.
      CONCLUSION: Because inguinal surgery for cryptorchidism may fail to disclose
      intraabdominal testes, surgery that has negative findings should be followed up
      by a close examination of the abdomen. Seminomas arising from an intraabdominal
      testis can be large and asymptomatic or may simulate other diseases. Torsion may
      occur and occasionally appear as acute abdomen. The imaging features can be
      nonspecific, and the history of cryptorchidism may not be provided. Awareness of
      the clinical and imaging features of neoplasms involving undescended
      intraabdominal testes is important for appropriate diagnosis and therapy.

PMID- 9930797
TI  - Using helical CT to evaluate renal cell carcinoma in patients undergoing
      hemodialysis: value of early enhanced images.
AB  - OBJECTIVE: The purpose of this study was to evaluate early and delayed enhanced
      helical CT for revealing renal cell carcinoma in patients undergoing
      hemodialysis. MATERIALS AND METHODS: Over the course of 3 years, 630 chronic
      hemodialysis patients underwent early and delayed contrast-enhanced and
      unenhanced helical CT to detect renal cell carcinoma. Retrospective review showed
      that 23 of these patients later underwent either unilateral or bilateral
      nephrectomy. Two radiologists, unaware of the pathology results, independently
      reviewed these 23 examinations. The sensitivity and specificity of each early and
      delayed scan for revealing neoplasms were determined using pathology as the gold
      standard. The mean attenuation values of the neoplasms and parenchymas of end
      stage kidneys on both early and delayed enhanced images were also compared.
      RESULTS: Helical CT revealed 225 lesions, 24 of which were found to be renal cell
      carcinomas at pathology. Delayed enhanced helical CT failed to detect one
      papillary carcinoma in an end-stage kidney with acquired cysts. Three
      nonpapillary carcinomas were not detected on delayed scans, and one was missed on
      an early scan of a patient without acquired cysts. The sensitivity and
      specificity of early enhanced CT for revealing renal cell carcinoma were 96% and
      95%, respectively. In contrast, delayed enhanced CT achieved a sensitivity of 83%
      and a specificity of 94%. A significant difference in mean attenuation values
      between carcinomas and renal parenchymas was observed on the images with early
      enhancement but not on those with delayed enhancement (p < .0001). CONCLUSION:
      Early enhanced helical CT is superior to delayed enhanced helical CT for
      revealing renal cell carcinoma in end-stage kidneys.

PMID- 9930798
TI  - Aggressive angiomyxoma: findings on CT and MR imaging.
AB  - OBJECTIVE: Aggressive angiomyxoma is a benign tumor affecting the pelvis and
      perineum, predominantly in women. Because of its variable presentation as a soft
      mass in the vulva, perianal region, buttock, or pelvis, the tumor is often
      clinically misdiagnosed and initial surgery is usually unsuccessful in
      extirpating it. This study describes the imaging features of these tumors.
      CONCLUSION: Aggressive angiomyxomas display unusual growth patterns of
      translevator extension with growth around perineal structures. Both CT and MR
      imaging show the transdiaphragmatic extent of these tumors. High signal intensity
      on T2-weighted MR images may reflect the myxomatous stroma of these tumors.

PMID- 9930799
TI  - Association of compartment defects in pelvic floor dysfunction.
AB  - OBJECTIVE: Dynamic cystoproctography was used to determine the frequency of
      associated urinary, genital, and anorectal abnormalities in women with pelvic
      floor dysfunction. SUBJECTS AND METHODS: We categorized, by pelvic floor
      compartments, the symptoms at presentation of 100 consecutive female patients who
      had been referred for dynamic cystoproctography. We then analyzed the compartment
      defects seen on dynamic cystoproctography relative to those detected on clinical
      presentation. RESULTS: Of the 20 patients with symptoms of anterior compartment
      (urinary) defect, dynamic cystoproctography revealed that 45% had vaginal vault
      prolapse of more than 50% and that 90% had rectoceles. Of the 45 patients with
      symptoms of middle compartment (genital) defect, dynamic cystoproctography
      revealed that 91% had cystoceles, 56% had a hypermobile bladder neck, 82% had
      rectoceles, 58% had enteroceles, 11% had sigmoidoceles, 20% had rectoanal
      intussusception, and 16% had anal incontinence. Of the 17 patients with symptoms
      of posterior compartment (anorectal) defect, dynamic cystoproctography showed
      that 71% had cystoceles, 65% had a hypermobile bladder neck, and 35% had vaginal
      vault prolapse of more than 50%. Of the 18 patients with symptoms of defects from
      a combination of compartments, dynamic cystoproctography revealed that 89% had
      cystoceles, 56% had a hypermobile bladder neck, 39% had vaginal vault prolapse
      exceeding 50%, 100% had rectoceles (of which 45% were large), 6% had enteroceles,
      6% had sigmoidoceles, 22% had rectoanal intussusception, and 6% had anal
      incontinence. CONCLUSION: Although patients may present with symptoms that
      involve only one compartment, a multicompartment prolapse is usually revealed on
      dynamic cystoproctography. Of the patients with pelvic floor dysfunction, 95% had
      abnormalities in all three compartments.

PMID- 9930800
TI  - Dermoid cysts of the ovary with malignant transformation: MR appearance.
AB  - OBJECTIVE: This study presents the MR appearances of five women with a total of
      six proven dermoid cysts of the ovary with malignant transformation. To our
      knowledge, the MR findings of this entity have not been reported. CONCLUSION: The
      lesions appeared to be fat-containing tumors with a solid component (4/6) that
      extended transmurally (4/6) and extensively invaded neighboring pelvic organs
      (3/6). The supervening malignancy was squamous cell carcinoma in four tumors,
      melanoma in one, and transitional cell carcinoma in one. The mode of spread
      differed from that of common ovarian tumors in that it included transmural
      extension and local invasion, reflecting squamous cell carcinoma.

PMID- 9930801
TI  - Coexistent surviving neonate twin and complete hydatidiform mole.

PMID- 9930802
TI  - Unfused crossed renal ectopia with ectopic left ureter inserting into a prostatic
      utricle diverticulum.

PMID- 9930803
TI  - Prognostic value of high-frequency sonography and color Doppler sonography for
      the preoperative assessment of melanomas.
AB  - OBJECTIVE: The purposes of this study were to determine the efficacy of high
      frequency sonography for the preoperative assessment of melanomas and to
      determine the prognostic value of tumor vascularity measured by color Doppler
      sonography. SUBJECTS AND METHODS: Twenty-seven patients with melanomas were
      prospectively examined using high-frequency sonography before they underwent
      surgery. For each tumor, morphologic evaluation (20-MHz probe), including the
      measurement of maximum tumor thickness, and color Doppler sonography analysis (13
      MHz probe), including the measurement of intratumor vascularity, were performed.
      Diagnosis was confirmed by histologic findings, tumor thickness was measured
      using the Breslow index, and vascularity was assessed by immunochemical findings.
      RESULTS: Each of the 27 melanomas was depicted on high-frequency sonography as a
      homogeneous hypoechoic structure with well-defined margins. Tumor thickness was
      measured using high-frequency sonography as ranging from 0.3 to 8.0 mm, whereas
      it was measured using the Breslow index as ranging from 0.26 to 8.0 mm.
      Sonography measurements and Breslow index values were strongly correlated (r >
      .95). In the cases in which the Breslow index value exceeded 1 mm (n = 11),
      surgical reexcision was necessary but could have been avoided if surgery had been
      planned on the basis of high-frequency sonography measurements. Intratumor
      vessels were depicted on color Doppler sonography (n = 10). Color Doppler
      sonography data and histologic findings were significantly correlated.
      CONCLUSION: High-frequency sonography is a simple, reliable, noninvasive, and
      accurate method for the preoperative measurement of melanoma thickness. In fact,
      surgical planning could be adapted according to this measurement. The prognostic
      value of vascularization evaluated with color Doppler sonography is comparable
      with that determined by the Breslow index.

PMID- 9930804
TI  - MR imaging for traumatic tears of the rotator cuff: high prevalence of greater
      tuberosity fractures and subscapularis tendon tears.
AB  - OBJECTIVE: The purpose of this study was to determine whether occult bony
      injuries or other characteristic MR abnormalities are frequent in patients
      suspected of having traumatic tears of the rotator cuff. SUBJECTS AND METHODS: MR
      arthrography of the shoulder was performed in 24 consecutive patients with
      suspected traumatic tears of the rotator cuff. MR findings were analyzed with
      regard to abnormalities of the supraspinatus, infraspinatus, and subscapularis
      tendons; and the humeral head. A comparison group of 24 consecutive patients with
      symptoms of nontraumatic tears of the rotator cuff was included in the
      investigation. RESULTS: Radiographically occult fractures of the greater
      tuberosity were found in nine (38%) of 24 patients with clinically suspected
      traumatic tears of the rotator cuff (seven of which occurred in patients <40
      years old). Nine partial-thickness and five full-thickness supraspinatus tears
      were found in the trauma group. In the comparison group, the corresponding
      numbers were 13 and 10, respectively. Seven partial lesions of the cranial border
      of the subscapularis and six complete subscapularis tears (all six in patients
      >40 years old) were found in the trauma group (nine and one in the comparison
      group). CONCLUSION: Occult greater tuberosity fractures and complete
      subscapularis tears are commonly seen on MR images in patients suspected of
      having traumatic tears of the rotator cuff. Greater tuberosity fractures should
      be looked for specifically in patients younger than 40 years, and subscapularis
      tears should be looked for specifically in patients older than 40 years.

PMID- 9930805
TI  - Occult fractures of the greater tuberosity of the humerus: radiographic and MR
      imaging findings.
AB  - OBJECTIVE: The purpose of this study is to discuss the clinical implications of
      diagnosing a one-part greater tuberosity fracture on radiography and to describe
      associated rotator cuff findings on MR imaging. CONCLUSION: One-part greater
      tuberosity fractures are traditionally treated conservatively. Because clinical
      findings simulate those of rotator cuff abnormalities, some patients with missed
      or nonvisible fractures may be referred for MR imaging for further examination.
      In our study, MR imaging revealed no associated cuff abnormalities that required
      early surgery. Diagnosis of such a fracture on radiography may obviate the need
      for unnecessary MR imaging and arthroscopic surgery.

PMID- 9930806
TI  - MR imaging of anterosuperior calcaneal process fractures.
AB  - OBJECTIVE: Fractures of the anterosuperior calcaneal process can be both
      clinically and radiographically difficult to detect yet, if not recognized and
      immobilized early, may result in painful nonunion. The purpose of this study was
      to show that MR imaging is sensitive in the detection of such subtle or
      radiographically occult fractures, that the pattern of marrow edema corresponds
      to the two known mechanisms of injury, and that MR imaging can document both
      healing and nonunion of these fractures. CONCLUSION: MR imaging can reveal subtle
      or nondisplaced fractures of the anterosuperior calcaneal process. Also, MR
      imaging can be used to document healing. The pattern of marrow edema limited to
      the anterosuperior calcaneal process corresponds to the bifurcate ligament
      avulsion mechanism of injury. Edema in both the anterosuperior calcaneal process
      and the cuboid is caused by the impaction mechanism of injury.

PMID- 9930807
TI  - The MR appearance of the infrapatellar plica.
AB  - OBJECTIVE: Our purpose is to describe the MR appearance and clinical relevance of
      the infrapatellar plica of the knee and to assess possible imaging pitfalls
      resulting from lack of recognition of this normal structure. Seven patients--four
      from our institution and three from our teaching file from outside institutions-
      were selected because they displayed the imaging features of the infrapatellar
      plica. CONCLUSION: The infrapatellar plica is readily appreciated on sagittal MR
      images of the knee as a low-signal-intensity structure in the intercondylar notch
      just anterior to the anterior cruciate ligament (ACL). The infrapatellar plica is
      important to recognize for the following reasons: It may be confused with an
      intact ACL because of its proximity and similar signal characteristics; it may
      pose difficulty to the arthroscopist when attempting to move instruments from the
      medial to lateral compartments of the knee; it can block clear visualization of
      the ACL during arthroscopy; and it can impair retrieval of loose bodies in the
      intercondylar notch. Familiarity with the infrapatellar plica should allow one to
      differentiate this normal structure from other structures in the knee and aid in
      preoperative planning.

PMID- 9930808
TI  - The effect of using shorter echo times in MR imaging of knee menisci: a study
      using a porcine model.
AB  - OBJECTIVE: Increasingly shorter TEs are being used for T1-weighted and proton
      density-weighted sequences in MR imaging of the knee. This study aims to evaluate
      the effect of a short TE on meniscal signal intensity. MATERIALS AND METHODS:
      Thirty porcine knees were imaged with a 1.5-T MR scanner using spin-echo T1
      weighted and proton density-weighted sequences. TR was kept constant at 700 msec
      for T1-weighted and 2200 msec for proton density-weighted sequences. For each set
      of sequences, sagittal images were obtained using these TE values: 9, 12, 16, 20,
      and 25 msec. Imaging parameters, such as slice thickness and interslice gap,
      number of excitations, matrix size, and field of view, were identical for each
      set of sequences. Using a fixed window level and width, we assessed the anterior
      and posterior horns of the medial meniscus for signal hyperintensity at each TE
      value. Signal intensity was also measured in eight knees. The menisci were then
      dissected and examined grossly and histopathologically. RESULTS: Intrameniscal
      signal intensity increased progressively with shorter TEs. At a TE of 9 msec,
      signal hyperintensity was present in 100% of T1-weighted and 96.7% of proton
      density-weighted images. At a TE of 12 msec, signal hyperintensity was seen in
      86.7% of T1-weighted and 80% of proton density-weighted images. At a TE of 16
      msec, increased signal intensity was seen in only 3.3% of T1-weighted and 6.6% of
      proton density-weighted images. At TEs of 20 and 25 msec, increased signal
      intensity was seen in none of the T1-weighted and proton density-weighted images.
      Meniscal signal intensity increased exponentially at very short TE values. All
      menisci were found to be normal on gross and histopathological examination.
      CONCLUSION: Spurious signal hyperintensity appears in normal menisci at short TE
      values. Images acquired with short TEs should be interpreted with caution, and a
      TE of 16 msec or more is recommended.

PMID- 9930809
TI  - Rapid osteolysis of the femoral neck after fracture.

PMID- 9930810
TI  - Experience with tunneled femoral hemodialysis catheters.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use and complication
      rate of tunneled femoral hemodialysis catheters placed in patients with no
      remaining thoracic venous access sites. MATERIALS AND METHODS: Over a 3-year
      period, 41 tunneled femoral vein catheters (35 right, six left) were placed in 21
      patients (15 women, six men; 21-89 years old; mean, 52 years). Catheters ranged
      in length from 40 to 60 cm. Tips were positioned immediately above the iliac
      bifurcation, at the mid inferior vena cava (IVC), or at the junction of the IVC
      and right atrium. Catheters were exchanged through the existing tract if the flow
      rate decreased to less than 200 ml/min. Catheters were removed if an episode of
      bacteremia did not resolve with antibiotics or if the insertion site became
      infected. RESULTS: Technical success of placement was 100%. The 30-, 60-, and 180
      day primary patency rates were 78%, 71%, and 55%, respectively. The 30-, 60-, and
      180-day secondary patency rates were 95%, 83%, and 61%, respectively. Average
      time of function per intervention was 61 days. Infections requiring catheter
      removal occurred at a rate of 2.4 per 1000 catheter days. One episode of partial
      IVC thrombosis occurred after a catheter infection developed 78 days after
      initial catheter placement. No episodes of symptomatic pulmonary embolism
      occurred. Total length of follow-up was 2506 catheter days. CONCLUSION: Femoral
      vein catheters require more frequent interventions than do thoracic catheters and
      are more susceptible to infection. However, in patients with difficult central
      venous access, the common femoral vein may be successfully used for permanent
      tunneled hemodialysis access.

PMID- 9930812
TI  - Use of a nitinol gooseneck snare to open an incompletely expanded over-the-wire
      stainless steel Greenfield filter.

PMID- 9930811
TI  - Combined use of portable CT and fluoroscopy in the angiography suite.

PMID- 9930813
TI  - Primary stenting in complete aortic occlusion.

PMID- 9930814
TI  - Maximizing the usefulness of imaging in children with community-acquired
      pneumonia.
AB  - In summary, imaging plays important roles in the diagnosis and treatment of
      children with community-acquired pneumonia. These roles include confirmation or
      exclusion of pneumonia, differentiation between viral and bacterial pneumonia,
      exclusion of other causes of symptoms, evaluation when the pneumonia fails to
      resolve, and evaluation of related complications.

PMID- 9930815
TI  - Impact of sonography on the diagnosis and treatment of acute lower abdominal pain
      in children and young adults.
AB  - OBJECTIVE: Our purpose was to evaluate the impact of sonographic data on clinical
      physicians' diagnostic confidence and their treatment of children and young
      adults with acute lower abdominal pain. SUBJECTS AND METHODS: Senior surgical and
      emergency department staff completed questionnaires before and after abdominal
      sonography was performed on 94 of 101 consecutive children and young adults with
      acute lower abdominal pain, pelvic pain, or both. Physicians who were unaware of
      sonographic data stated the most likely diagnosis and their level of confidence
      in their diagnosis and then formulated clinical plans. After they were given
      sonographic data, physicians again stated the most likely diagnosis, estimated
      their level of confidence, and formulated revised treatment plans. RESULTS:
      Sonographic data resulted in revised clinical diagnoses in 52% of the patients.
      Overall, the gain in diagnostic confidence for the entire study population was
      33% (95% confidence interval [CI], 27-38%; p < .0001). The impact on the
      physicians' confidence was greater in those children and young adults whose
      diagnoses changed after sonography (mean increase in physicians' confidence,
      48.3%; 95% CI, 47-75%). In patients whose diagnoses were not changed after
      sonography, the mean increase in physicians' confidence was 17.6% (95% CI, 11
      24%; p < .0001 [analysis of variance]). Physicians used sonographic data to
      change initial treatment plans in 43 patients (46%). Of these 43 patients, a
      lower intensity of care was given to 30 patients (70%) and a higher intensity to
      13 patients (30%). CONCLUSION: Sonographic data frequently changed initial
      clinical diagnoses, thus increasing diagnostic confidence and changing clinical
      treatment decisions in the setting of acute lower abdominal pain in children and
      young adults.

PMID- 9930816
TI  - Atypical presentation of Clostridium difficile colitis in patients with cystic
      fibrosis.
AB  - OBJECTIVE: This report describes the unusual presentation of Clostridium
      difficile colitis in five patients with cystic fibrosis and the role of CT in
      first suggesting the correct diagnosis in this group of patients. Because of the
      absence of watery diarrhea and the presence of abdominal bloating and decreased
      stooling, cystic fibrosis patients with C. difficile colitis will be treated for
      stool impaction, meconium ileus equivalent, or distal intestinal obstruction
      syndrome. CT of the abdomen, performed in these five patients because of their
      lack of improvement after standard therapy for stool impaction, showed an
      extensive pancolitis later confirmed to be caused by C. difficile infection.
      CONCLUSION: In patients with cystic fibrosis, imaging findings of a pancolitis
      should raise the possibility of C. difficile colitis despite the lack of watery
      diarrhea. Anticlostridial treatment can be initiated before bacteriologic
      confirmation is obtained.

PMID- 9930817
TI  - Sonographic evaluation of fetal CNS: technical and interpretive pitfalls.

PMID- 9930818
TI  - Clinical usefulness of T2-weighted fluid-attenuated inversion recovery MR imaging
      of the CNS.

PMID- 9930819
TI  - Use of MR exponential diffusion-weighted images to eradicate T2 "shine-through"
      effect.

PMID- 9930820
TI  - Delayed cerebral artery pseudoaneurysm after nail gun injury.

PMID- 9930821
TI  - Inverted papilloma of the nasal cavity and the paranasal sinuses: using CT for
      primary diagnosis and follow-up.
AB  - OBJECTIVE: Morphologic criteria for the diagnosis of primary and recurrent
      inverted papilloma as revealed on CT were evaluated in a large series. MATERIALS
      AND METHODS: Findings of 121 CT examinations that had been performed in 32
      patients with histologically proven inverted papilloma were retrospectively
      analyzed using the following morphologic criteria: localization, size, surface
      configuration, and bony changes. RESULTS: Unilateral tumor localization involving
      the lateral nasal wall and the middle meatus was the feature that best correlated
      with the finding of primary inverted papilloma. A lobulated surface pattern was
      another typical sign, which was revealed on 19 of the 29 CT scans of patients
      with primary inverted papilloma. Although tumor localization and the finding of a
      newly grown soft-tissue mass were less reliable criteria to differentiate between
      recurrent inverted papilloma and postoperative complications or concomitant
      inflammatory disease, a lobulated surface pattern was seen on 26 of the 28 CT
      scans of patients with tumor recurrence but on only three of the 64 follow-up CT
      scans of patients without recurrent inverted papilloma. CONCLUSION: A unilateral
      mass within the nasal cavity or paranasal sinuses with a surface configuration
      that appears lobulated on CT is, to our knowledge, a new sign that strongly
      suggests inverted papilloma as a primary diagnosis and also suggests inverted
      papilloma in patients with tumor recurrence.

PMID- 9930822
TI  - Round pneumonia and focal organizing pneumonia are different entities.

PMID- 9930823
TI  - Traumatic elbow effusions.

PMID- 9930824
TI  - Fatty mass of the pancreas is not equal to lipoma of the pancreas.

PMID- 9930825
TI  - Software for nervous teachers.

PMID- 9930826
TI  - Symptomatic neuroepithelial (ependymal) cyst of the fourth ventricle: MR
      appearance.

PMID- 9930827
TI  - Sarcoidosis of the breast presenting as a spiculated lesion.

PMID- 9930828
TI  - MR appearance of penile epithelioid sarcoma.

PMID- 9930829
TI  - Spondylolysis of the axis vertebra: a rare anomaly simulating hangman's fracture.

PMID- 9930830
TI  - Abscess complicating colic adenocarcinoma and leading to systemic venous air
      embolization.

PMID- 9930831
TI  - Depiction of an endoleak after abdominal aortic stent-grafting with contrast
      enhanced three-dimensional MR angiography.

PMID- 9930832
TI  - Robotic recovery of highly radioactive resin.
AB  - As the ALARA coordinator at Waterford 3 Nuclear Steam Electric Station, I have
      seen radiological challenges in many forms. Some are handled as routine with
      little effort, while others can severely challenge even the finest Health Physics
      staff. One such event occurred on 26 December 1997, during a routine
      recirculation of the Spent Resin Tank, when contents of an unknown origin spilled
      from the tank. Technicians performing initial actions to contain the spill
      monitored radiation levels of 5-20 rem h21 (50-200 mSv) at waist level. Based on
      photographs and visual accounts it was estimated that approximately 30-40 ft3
      (0.57-1.12 m3) of resin had spilled into the pump room. A sample of the resin
      indicated that dose rates at the floor would exceed 100 rem h21 (1 Sv h21). It
      was clear, given the volume of material spilled and dose rates in the room, that
      robots would be required for any type of recovery effort. This presented another
      problem in that Waterford 3 did not own a robot, and we had no experience in this
      area.

PMID- 9930833
TI  - Radiation safety instruction for non-radiation workers.
AB  - In today's society, neglecting to provide adequate hazard-awareness instruction
      to workers can be successfully used to file suit against institutions where
      radioactive material (RAM) or radiation generating devices (RGDs) are used.
      Because of the lack of instruction, in some cases, just the perceived risk (even
      where no significant exposure to radiation existed) has proven to be more
      important than the actual risk. Groups of non-radiation workers such as
      custodian, maintenance and laboratory personnel, whose duties may require them to
      work in the vicinity of RAM and RGDs, sometimes do not receive proper hazard
      awareness instruction. Misinterpretation of the applicable hazard-awareness
      regulations is a reason why institutions sometimes fail to instruct their
      workers. The objectives of this paper are to help radiation safety program
      managers become more aware of the importance of having well-instructed non
      radiological personnel and to develop and provide basic information to help
      implement an effective hazard-awareness instruction program for workers. Topics
      discussed in this paper include regulatory aspects regarding the instruction to
      non-radiation workers, a list of radiological incidents that could have been
      prevented with proper instruction to workers and recommendations for the
      development and implementation of an effective instruction program.

PMID- 9930834
TI  - Effective presentation of radiation safety training--risk communication: an
      important function of radiation safety training.
AB  - Implementing an effective radiation safety program requires good communication
      with workers. The process begins with radiation safety. Before workers take a
      position involving radiation exposures, they should understand the possible
      health risks and what to do to keep their risks ALARA. The goal is for workers to
      achieve a balanced perspective on radiation health risks in order to avoid either
      undue fear or undue complacency about radiation. Workers should have enough
      understanding of radiation risks to decide to acceptor not accept-or not accept
      the risk of radiation as a condition of employment. Furthermore, the decision to
      accept radiation risk for the benefits of employment should be based on informed
      consent. Workers with a good understanding of radiation health risks will strive
      to minimize not only their own radiation exposure but also those of their work
      group. Normally radiation safety training to achieve worker understanding is
      focused primarily on the technology of radiation. However, understanding is more
      than a matter of good technical information. What one chooses to understand is
      also impacted by perceptions of radiation risks.

PMID- 9930835
TI  - Unwanted radioactive sources in the public domain: a historical perspective.
AB  - In the 1920's, reports of radium sources entering the public domain in an
      uncontrolled manner began to appear in the press and in the literature.
      Additionally, gold jewelry was made from depleted radon gold seeds which, in some
      cases, resulted in radiation injuries to the persons wearing the jewelry. Such
      jewelry was made as early as 1910. For many years, radium was distributed and
      used largely without regulatory oversight for safety. In the 1950's, increasing
      concern over the radiation hazards associated with the inadequate use, control,
      and disposal of radium sources resulted in increased regulatory oversight by the
      States, with significant assistance from the U.S. Public Health Service. In 1958,
      the U.S. Atomic Energy Commission staff proposed extension of the general license
      concept to include measuring, gauging, and controlling devices. Since then, more
      than 1.8 million radioactive devices have been distributed under the general
      licenses in 10 CFR Part 31.5 and equivalent Agreement State regulations. These
      devices are typically used with minimal regulatory oversight. In recent years
      there has been an increasing number of reports of radioactive sources and devices
      appearing in the public domain as a result of inadequate control and disposal of
      these items with attendant risk of environmental contamination and radiation
      exposure. As a result of concerns over these developments there have been calls
      for increased regulatory oversight of general licensees. It is ironic that the
      present problems are the result of a program that was established about the time
      that States were increasing regulatory oversight over radium to address similar
      problems with radium.

PMID- 9930836
TI  - Benchmarking radiation protection programs.
AB  - Results are presented of a modest benchmarking project with eight institutions as
      part of a program review. Four of the institutions had programs with both
      research and clinical components. Metrics were derived from the data acquired.
      They included Registered Users per total Technical Staff (mean 284, SD 42%);
      Principal Investigators per Senior IP staff (mean 68.7, SD 49.6%); and Principal
      Investigators per HP staff (mean 44.7, SD 34.4%). Reasons for the differences
      among institutions were identified. The benchmarking exercise was an effective
      tool in providing guidance in setting staffing levels.

PMID- 9930837
TI  - Reorganization and consolidation of a safety program.
AB  - Prior to 1990, the Mayo Safety Program consisted of several autonomous functions,
      one of which was Radiation Safety. Consolidation and enhancement of these
      programs began in 1990 with safety coordinators (e.g., health physicists,
      industrial hygienists, ergonomists) reporting to one safety director who reports
      to a vice president level administrator. In 1995, the hierarchical structure was
      replaced with self-directed work teams. These teams have team leaders who
      replaced conventional work unit supervisors and a Human Resources (HR) Liaison
      who is responsible for HR issues including time keeping and 360 degrees
      performance reviews. A Steering Team, consisting of team leaders was established
      to create a strategic plan, set program goals, and hold teams accountable. In
      1997, processes were evaluated and redesigned through an operational
      restructuring method called process mapping; process mapping is a tool used in
      reengineering. Value added to the safety program as a result of these efforts
      includes more program ownership by Safety staff as demonstrated by increased
      motivation, increased interest in success of the entire safety program, and
      increased participation in team planning and management. In addition, some
      economies of scale have been achieved through cross-functional teams.

PMID- 9930838
TI  - Adding water to liquid scintillation cocktail for laboratory wipe tests.
AB  - As part of an ongoing laboratory survey process improvement program, we evaluated
      the addition of water to liquid scintillation cocktail to improve wipe test
      counting efficiency. Both polar and non-polar 3H and 14C-labeled compounds were
      used as model contaminants. Our results support the recommendations in the
      literature regarding the addition of water to scintillation cocktail We found an
      increase in the counting efficiency of the water-soluble material as a function
      of water content of the cocktail, but also observed a decrease in the efficiency
      of detection of the non-polar compound. The offsetting effects are believed to be
      the result of increased solubility of the polar compounds in water and increased
      quench of the already solubilized non-polar compound. The finding that adding
      water to the cocktail brought counting efficiencies of both polar and non-polar
      molecules to roughly the same value is novel and allows the use of a single
      quench curve for each radionuclide, regardless of chemical form.

PMID- 9930839
TI  - Tritium dose overestimates by CAP88-PC.
AB  - The dose assessment software CAP88-PC may overestimate doses from tritium under
      some conditions. The overestimates are linked to three key assumptions implicit
      in the software that may not be immediately parent. The three assumptions are (1)
      the contribution of home grown food, (2) the distances at which food is produced,
      and (3) the number of people consuming locally produced food.

PMID- 9930840
TI  - Variations in dose to the extremities of vascular/interventional radiologists.
AB  - An evaluation was performed to determine the distribution of radiation dose
      received by vascular/interventional radiologists, hence forth called
      radiologists, to their hands and arms during interventional radiology procedures.
      During 87 patient procedures, measurements were made using thermoluminescent
      dosimeters to determine the distribution of dose to the hands and forearms.
      Measurements were made on a finger, the palm, wrist, elbow, and the mid-humerus
      of both hands and arms. Results suggested a non-uniformity of dose with the
      maximum dose being measured on the left hypothenar (fleshy side of the palm). The
      left hand receives a higher dose than the right hand due to positioning of the
      radiologist with respect to the patient.

PMID- 9930842
TI  - Tobacco money and medical research.

PMID- 9930841
TI  - Communicating effectively with regulatory agencies in the licensing process.
AB  - Planning preparing, submitting and tracking license and permit applications
      through the regulatory process is complex and time consuming. A disciplined
      approach can make the process easier. This paper discusses practical steps to
      take and some guidelines to follow in making the licensing or permitting process
      easier.

PMID- 9930843
TI  - The dangers of DNA vaccination.

PMID- 9930844
TI  - Diabetes and the risk of miscarriage.

PMID- 9930845
TI  - Anti-tumor activity of C-raf antisense--correction.

PMID- 9930846
TI  - CRC forced to compromise over tobacco funding ban.

PMID- 9930847
TI  - NIH opens conflict-of-interest investigation.

PMID- 9930848
TI  - Can research survive at MCPHU--the new Allegheny?

PMID- 9930849
TI  - Britain excels in academic capitalism.

PMID- 9930850
TI  - Italy labors in its reform of the CNR.

PMID- 9930851
TI  - Australian report favors more monkey business.

PMID- 9930852
TI  - The challenge of private biomedical research funding in Italy.

PMID- 9930853
TI  - Delivering genes to the heart--right where it counts!

PMID- 9930854
TI  - HIV-1 neutralizing antibodies: how full is the bottle?

PMID- 9930855
TI  - Endotoxin opens the Tollgates to innate immunity.

PMID- 9930856
TI  - The TRAIL to selective tumor death.

PMID- 9930857
TI  - The pandemic of antibiotic resistance.

PMID- 9930858
TI  - A partnership that delivers.

PMID- 9930859
TI  - Human embryonic stem cells: the future is now.

PMID- 9930860
TI  - Remembering MOG: autoantibody mediated demyelination in multiple sclerosis?

PMID- 9930861
TI  - Live attenuated AIDS vaccines: hazards and hopes.

PMID- 9930862
TI  - Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand
      in vivo.
AB  - To evaluate the utility of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of
      human (hu) and murine (mu) TRAIL to promote and stabilize the formation of
      trimers. Both were biologically active, inducing apoptosis of both human and
      murine target cells in vitro with similar specific activities. In contrast to the
      fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ
      huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally,
      repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL
      sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice,
      and histologic examination of tumors from SCID mice treated with LZ-huTRAIL
      demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.

PMID- 9930863
TI  - Presenilin mutations associated with Alzheimer disease cause defective
      intracellular trafficking of beta-catenin, a component of the presenilin protein
      complex.
AB  - The presenilin proteins are components of high-molecular-weight protein complexes
      in the endoplasmic reticulum and Golgi apparatus that also contain beta-catenin.
      We report here that presenilin mutations associated with familial Alzheimer
      disease (but not the non-pathogenic Glu318Gly polymorphism) alter the
      intracellular trafficking of beta-catenin after activation of the Wnt/beta
      catenin signal transduction pathway. As with their effect on betaAPP processing,
      the effect of PS1 mutations on trafficking of beta-catenin arises from a dominant
      'gain of aberrant function' activity. These results indicate that mistrafficking
      of selected presenilin ligands is a candidate mechanism for the genesis of
      Alzheimer disease associated with presenilin mutations, and that dysfunction in
      the presenilin-beta-catenin protein complexes is central to this process.

PMID- 9930864
TI  - Identification of autoantibodies associated with myelin damage in multiple
      sclerosis.
AB  - The molecular mechanisms underlying myelin sheath destruction in multiple
      sclerosis lesions remain unresolved. With immunogold-labeled peptides of myelin
      antigens and high-resolution microscopy, techniques that can detect antigen
      specific antibodies in situ, we have identified autoantibodies specific for the
      central nervous system myelin antigen myelin/oligodendrocyte glycoprotein. These
      autoantibodies were specifically bound to disintegrating myelin around axons in
      lesions of acute multiple sclerosis and the marmoset model of allergic
      encephalomyelitis. These findings represent direct evidence that autoantibodies
      against a specific myelin protein mediate target membrane damage in central
      nervous system demyelinating disease.

PMID- 9930865
TI  - Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs
      by arresting fibronectin-dependent neointimal formation.
AB  - Closure of the ductus arteriosus requires prenatal formation of intimal cushions,
      which occlude the vessel lumen at birth. Survival of newborns with severe
      congenital heart defects, however, depends on ductal patency. We used a gene
      transfer approach to create a patent ductus arteriosus by targeting the
      fibronectin-dependent smooth muscle cell migration required for intimal cushion
      formation. Fetal lamb ductus arteriosus was transfected in utero with
      hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA
      to sequester the fibronectin mRNA binding protein. Fibronectin translation was
      inhibited and intimal cushion formation was prevented. We thus established the
      essential role of fibronectin-dependent smooth muscle cell migration in intimal
      cushion formation in the intact animal and the feasibility of incorporating
      biological engineering in the management of congenital heart disease.

PMID- 9930866
TI  - Molecular basis for resistance to silver cations in Salmonella.
AB  - Here we report the genetic and proposed molecular basis for silver resistance in
      pathogenic microorganisms. The silver resistance determinant from a hospital burn
      ward Salmonella plasmid contains nine open reading frames, arranged in three
      measured and divergently transcribed RNAs. The resistance determinant encodes a
      periplasmic silver-specific binding protein (SilE) plus apparently two parallel
      efflux pumps: one, a P-type ATPase (SilP); the other, a membrane potential
      dependent three-polypeptide cation/proton antiporter (SilCBA). The sil
      determinant is governed by a two-component membrane sensor and transcriptional
      responder comprising silS and silR, which are co-transcribed. The availability of
      the sil silver-resistance determinant will be the basis for mechanistic molecular
      and biochemical studies as well as molecular epidemiology of silver resistance in
      clinical settings in which silver is used as a biocide.

PMID- 9930867
TI  - Requirement for multiple lymphocyte subsets in protection by a live attenuated
      vaccine against retroviral infection.
AB  - Infection by live attenuated retroviruses provides excellent protection from
      challenge with pathogenic viruses in several animal models, but little is known
      about which immune effectors are necessary for protection. We examined this using
      adoptive transfer experiments in the Friend virus mouse model. Transfers of
      immune spleen cells into naive mice conferred complete protection, and transfers
      of purified lymphocyte subsets demonstrated that this effect required complex
      immune responses involving CD4+ and CD8+ T cells and also B cells. In addition,
      passive immunization experiments demonstrated that antibodies alone reduced virus
      loads but did not prevent infection. These findings may have implications for
      retroviral vaccine design in general.

PMID- 9930868
TI  - Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in
      infant and adult macaques.
AB  - A substantial risk in using live attenuated, multiply deleted viruses as vaccines
      against AIDS is their potential to induce AIDS. A mutant of the simian
      immunodeficiency virus (SIV) with large deletions in nef and vpr and in the
      negative regulatory element induced AIDS in six of eight infant macaques
      vaccinated orally or intravenously. Early signs of immune dysfunction were seen
      in the remaining two offspring. Prolonged follow-up of sixteen vaccinated adult
      macaques also showed resurgence of chronic viremia in four animals: two of these
      developed early signs of disease and one died of AIDS. We conclude that this
      multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar
      prototypes may cause AIDS.

PMID- 9930869
TI  - Neutralizing antibody directed against the HIV-1 envelope glycoprotein can
      completely block HIV-1/SIV chimeric virus infections of macaque monkeys.
AB  - Virus-specific antibodies protect individuals against a wide variety of viral
      infections. To assess whether human immunodeficiency virus type 1 (HIV-1)
      envelope-specific antibodies confer resistance against primate lentivirus
      infections, we purified immunoglobulin (IgG) from chimpanzees infected with
      several different HIV-1 isolates, and used this for passive immunization of pig
      tailed macaques. These monkeys were subsequently challenged intravenously with a
      chimeric simian-human immunodeficiency virus (SHIV) bearing an envelope
      glycoprotein derived form HIV-1DH12, a dual-tropic primary virus isolate. Here we
      show that anti-SHIV neutralizing activity, determined in vitro using an assay
      measuring loss of infectivity, is the absolute requirement for antibody-mediated
      protection in vivo. Using an assay that measures 100% neutralization, the titer
      in plasma for complete protection of the SHIV-challenged macaques was in the
      range of 1:5-1:8. The HIV-1-specific neutralizing antibodies studied are able to
      bind to native gp120 present on infectious virus particles. Administration of non
      neutralizing anti-HIV IgG neither inhibited nor enhanced a subsequent SHIV
      infection.

PMID- 9930870
TI  - Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance
      of cell-free virions from blood plasma.
AB  - The concentration of human immunodeficiency virus type 1 (HIV-1) particles in
      blood plasma is very predictive of the subsequent disease course in an infected
      individual; its measurement has become one of the most important parameters for
      monitoring clinical status. Steady-state virus levels in plasma reflect a balance
      between the rates of virions entering and leaving the peripheral blood. We
      analyzed the rate of virus clearance in the general circulation in rhesus
      macaques receiving a continuous infusion of cell-free particles in the presence
      and absence of virus-specific antibodies. Here we show, by measuring virion RNA,
      particle-associated p24 Gag protein and virus infectivity, that the clearance of
      physical and infectious particles from a primary, dual-tropic virus isolate, HIV
      1DH12, is very rapid in naive animals, with half-lives ranging from 13 to 26
      minutes. In the presence of high-titer HIV-1DH12-specific neutralizing
      antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2
      minutes), and infectious virus in the blood became undetectable. Although
      physical virus particles were eliminated extravascularly, the loss of virus
      infectivity in the blood reflected the combined effects of extravascular
      clearance and intravascular inactivation of HIV-1 infectivity due to antibody
      binding.

PMID- 9930871
TI  - Salt-sensitive hypertension and reduced fertility in mice lacking the
      prostaglandin EP2 receptor.
AB  - Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase
      metabolism of arachidonic acid that exert a broad range of physiologic
      activities, including modulation of inflammation, ovulation and arterial blood
      pressure. PGE2, a chief cyclooxygenase product, modulates blood pressure and
      fertility, although the specific G protein-coupled receptors mediating these
      effects remain poorly defined. To evaluate the physiologic role of the PGE2 EP2
      receptor subtype, we created mice with targeted disruption of this gene (EP2-/-).
      EP2-/- mice develop normally but produce small litters and have slightly elevated
      baseline systolic blood pressure. In EP2-/- mice, the characteristic hypotensive
      effect of intravenous PGE2 infusion was absent; PGE2 infusion instead produced
      hypertension. When fed a diet high in salt, the EP2-/- mice developed profound
      systolic hypertension, whereas wild-type mice showed no change in systolic blood
      pressure. Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated
      that the reduced litter size of EP2-/- mice is due to a pre-implantation defect.
      This reduction of implanted embryos could be accounted for by impaired ovulation
      and dramatic reductions in fertilization observed on day 2 of pregnancy. These
      data demonstrate that the EP2 receptor mediates arterial dilatation, salt
      sensitive hypertension, and also plays an essential part in female fertility.

PMID- 9930872
TI  - An essential part for Rho-associated kinase in the transcellular invasion of
      tumor cells.
AB  - Adhesion of tumor cells to host cell layers and subsequent transcellular
      migration are pivotal steps in cancer invasion and metastasis. The small GTPase
      Rho controls cell adhesion and motility through reorganization of the actin
      cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1
      hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum
      dependent, Rho-mediated manners. Among several proteins isolated as putative
      target molecules of Rho, the ROCK (ROK) family of Rho-associated serine-threonine
      protein kinases are thought to participate in the induction of focal adhesions
      and stress fibers in cultured cells, and to mediate calcium sensitization of
      smooth muscle contraction by enhancing phosphorylation of the regulatory light
      chain of myosin. Transfection of MM1 cells with cDNA encoding a dominant active
      mutant of ROCK conferred invasive activity independently of serum and Rho. In
      contrast, expression of a dominant negative, kinase-defective ROCK mutant
      substantially attenuated the invasive phenotype. A specific ROCK inhibitor (Y
      27632) blocked both Rho-mediated activation of actomyosin and invasive activity
      of these cells. Furthermore, continuous delivery of this inhibitor using osmotic
      pumps considerably reduced the dissemination of MM1 cells implanted into the
      peritoneal cavity of syngeneic rats. These results indicate that ROCK plays an
      essential part in tumor cell invasion, and demonstrate its potential as a
      therapeutic target for the prevention of cancer invasion and metastasis.

PMID- 9930873
TI  - Hepatocyte growth factor gene therapy of liver cirrhosis in rats.
AB  - Liver cirrhosis is the irreversible end result of fibrous scarring and
      hepatocellular regeneration, characterized by diffuse disorganization of the
      normal hepatic structure of regenerative nodules and fibrotic tissue. It is
      associated with prominent morbidity and mortality, and is induced by many
      factors, including chronic hepatitis virus infections, alcohol drinking and drug
      abuse. Hepatocyte growth factor (HGF), originally identified and cloned as a
      potent mitogen for hepatocytes, shows mitogenic, motogenic and morphogenic
      activities for a wide variety of cells. Moreover, HGF plays an essential part in
      the development and regeneration of the liver, and shows anti-apoptotic activity
      in hepatocytes. In a rat model of lethal liver cirrhosis produced by
      dimethylnitrosamine administrations, repeated transfections of the human HGF gene
      into skeletal muscles induced a high plasma level of human as well as enodogenous
      rat HGF, and tyrosine phosphorylation of the c-Met/HGF receptor. Transduction
      with the HGF gene also suppressed the increase of transforming growth factor
      beta1 (TGF-beta1), which plays an essential part in the progression of liver
      cirrhosis, inhibited fibrogenesis and hepatocyte apoptosis, and produced the
      complete resolution of fibrosis in the cirrhotic liver, thereby improving the
      survival rate of rats with this severe illness. Thus, HGF gene therapy may be
      potentially useful for the treatment of patients with liver cirrhosis, which is
      otherwise fatal and untreatable by conventional therapy.

PMID- 9930874
TI  - A co-stimulatory signal through ICAM-beta2 integrin-binding potentiates
      neutrophil phagocytosis.
AB  - The beta2 integrin LFA-1 (lymphocyte function associated antigen; CD11a/CD18) is
      the common ligand for the intercellular adhesion molecules (ICAMs). Integrins
      support cell function by providing co-stimulatory second signals that are a
      precondition for full cell activation first described for ICAM-1-binding to LFA-1
      in lymphocytes. Integrins can also serve to activate functions associated with
      distinct subunits of other integrins. In addition to LFA-1, neutrophils express
      the beta2 integrin Mac-1 (CD11b/CD18; CR3) that apparently contains multiple
      sites that bind invading microbes directly or through surface-fixed C3, resulting
      in activation of the phagocyte function. Expression of the LFA-1 counter-receptor
      ICAM-1 on endothelial cells occurs only at the site of inflammation. Therefore,
      in neutrophils, ICAM-1 ligand binding could, as with lymphocytes, also play a
      part as a co-stimulatory signal to induce full phagocytotic function. We show
      that in neutrophils, the LFA-1 ligand interaction is the stimulatory signal to
      express full phagocytotic activation. This is best demonstrated by the rapid
      association of Streptococcus pyogenes with neutrophils, followed by ingestion,
      strong oxidative-burst induction and enhanced killing of these bacteria, which
      are well-known for their resistance to human neutrophil defense. These findings
      may contribute to the development of therapeutic strategies targeting the
      modulation of ICAM-1-leukocyte interaction.

PMID- 9930875
TI  - Functional cardiac imaging in mice using Ta-178.

PMID- 9930876
TI  - PCR-mediated recombination: a general method applied to construct chimeric
      infectious molecular clones of plasma-derived HIV-1 RNA.
AB  - A PCR-based approach was developed that provides a powerful tool for engineering
      recombinant molecules without reliance on restriction sites. DNA sequences were
      first amplified by high-fidelity PCR using Pfu polymerase; they were then used
      both as 'megaprimers' and templates in subsequent asymmetric long PCR
      amplifications to form chimeric clones. To demonstrate the technique, we
      constructed chimeric full-length HIV-1 clones derived from reverse-transcribed
      plasma viral RNA and proviral LTRs. Biologic characterization of these clones
      showed that most were infectious in tissue culture and sequence analysis
      demonstrated an error rate of only one base change in 20 kb of DNA sequence. For
      PCR-mediated recombination, it is necessary to know the sequence of the 3' and 5'
      overlapping regions of the desired PCR products. This method may be extended to
      include construction of chimeras between any DNA fragments lacking sequence
      homology. Such chimeras may be constructed by introducing overlapping sequences
      to one of the fragments. To ensure that unwanted mutations have not been
      introduced into the clones constructed by this method, each clone should be
      sequenced. Our results demonstrate that by using a high-fidelity polymerase and
      highly controlled PCR conditions, the PCR-introduced error rate can be greatly
      minimized. This new procedure may be used to construct infectious chimeras of HIV
      or SIV for studies of vaccines and pathogenesis. Moreover, the method is designed
      to exchange viral genes at precise boundaries to study individual gene products
      from different HIV genomes. It can also be used to construct expression vectors
      for production of specific proteins or delivery vectors for gene transfer and
      gene therapy. Finally, the technique described here provides a versatile tool to
      transfer genes or gene fragments from different sources for genetic investigation
      and engineering.

PMID- 9930877
TI  - Localization in situ of type VI collagen protein and its mRNA in mesangial
      proliferative glomerulonephritis using renal biopsy sections.
AB  - Extracellular matrix accumulation is crucial in the pathogenesis of
      glomerulosclerosis in mesangial proliferative glomerulonephritis (GN). In an
      attempt to explore the distribution of type VI collagen and its synthesizing
      cells in normal and diseased glomeruli, we investigated mRNA and protein
      expression of type VI collagen in renal biopsy sections, histologically diagnosed
      as mesangial proliferative GN. Five renal biopsies from patients diagnosed as
      having minor glomerular abnormalities and one surgical renal tissue were also
      simultaneously examined as controls. Immunohistochemical studies revealed type VI
      collagen immunostaining in the mesangium and glomerular basement membrane of the
      control glomeruli. Compared to the control, increased deposition of type VI
      collagen was noted in the mesangial proliferative and sclerotic lesions in GN. To
      identify the cells responsible for the synthesis of type VI collagen mRNA, renal
      sections were hybridized in situ with digoxigenin-labeled antisense oligo-DNA
      probe complementary to a part of alpha1 (VI) mRNA. Occasionally intraglomerular
      cells hybridized with digoxigenin-labeled antisense pro alpha1 (VI) oligo-DNA in
      control glomeruli. An increased number of intraglomerular cells (mostly
      epithelial cells) were, however, positive for alpha1 (VI) mRNA expression in GN
      sections. The present study documents the distribution of type VI collagen in the
      normal glomeruli and provides further evidence of accelerated synthesis of this
      collagen in mesangial proliferative GN.

PMID- 9930879
TI  - Immunohistochemical localization of vascular endothelial growth factor in the
      globule leukocyte/mucosal mast cell of the rat respiratory and digestive tracts.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic mitogen that
      also increases vascular permeability. Immunohistochemical localization of VEGF in
      the respiratory and digestive tracts of healthy adult rats was investigated at
      light and electron microscopic levels using a specific antibody. The results
      revealed solitary cells with strong VEGF immunoreactivity scattered in the
      epithelium of the respiratory tract as well as in the lamina propria and
      epithelium of the intestine. From ultrastructural features of their large
      cytoplasmic granules, VEGF-positive cells in the respiratory tract were
      identified as globule leukocytes (GL). The immunoreactivity was localized
      exclusively in the cytoplasmic granules of GL. Most of the VEGF-positive cells in
      the small intestine were located in the lamina propria, whereas those in the
      large intestine were found more frequently in the epithelium than in the lamina
      propria. They showed the same morphological features as respiratory tract GL and
      were identified as mucosal mast cells (MMC). When examined in serial sections,
      GL/MMC in the respiratory and digestive tracts showed only weak reactivity to
      anti-histamine antibody. In contrast, connective tissue mast cells (CTMC), which
      were located in the submucosa of the digestive tract and in the connective
      tissues of the respiratory tract and other organs, were intensely immunopositive
      for histamine, whereas they showed no reactivity to anti-VEGF antibody. The
      specific occurrence of VEGF in GL/MMC suggests that this cell type is involved in
      paracrine regulation of the permeability of nearby microvessels, and that VEGF
      immunoreactivity can be used as a histochemical marker to distinguish GL/MMC from
      CTMC.

PMID- 9930878
TI  - In situ hybridization with polymerase chain reaction-derived single-stranded DNA
      probe and S1 nuclease.
AB  - A rapid and simplified protocol for in situ hybridization (ISH) with polymerase
      chain reaction (PCR)-derived single-stranded DNA probes and S1 nuclease revealed
      transcripts of bone matrix proteins on decalcified skeletal bone specimens. Mouse
      bone tissue was fixed with 4% paraformaldehyde, decalcified with 20% EDTA, and
      embedded in paraffin. Each pair of primers for reverse transcriptase -PCR was
      designed to amplify a 280-bp DNA fragment from the coding region of the mature
      protein of mouse osteonectin (ON) and a 320-bp fragment from the coding region of
      mouse osteopontin (OP). Initial PCR products were eluted, purified, and
      reamplified by unidirectional PCR in the presence of the digoxigenin (DIG)
      labeled dUTP. ISH was carried out by proteinase K treatment, hybridization, and
      washing. The unhybridized single-stranded DNA probe was selectively removed by S1
      nuclease treatment. Hybridized probes were visualized with the alkaline
      phosphatase-conjugated anti-DIG antibody. The transcripts of ON and OP were
      clearly detected on the thin sections of the decalcified bone. Because this
      protocol does not require cloning or in vitro transcription, reliable and stable
      ISH can be done in an ordinary laboratory equipped with a thermal cycler.

PMID- 9930880
TI  - Differential distribution of lectin-binding glycoconjugates in the secretory
      granules of hamster oviductal ampulla during the estrous cycle: a quantitative
      cytochemical analysis.
AB  - High resolution lectin-gold cytochemistry was used to quantitatively analyze the
      distribution of glycoconjugates in the hamster oviductal ampulla during the five
      stages of the estrous cycle. Lectins binding to N-acetyl-D-galactosamine-, D
      galactose-, and sialic acid-associated glycoconjugates in the secretory granules
      of ampullary epithelial secretory cells showed staining of equal intensity
      throughout the five different stages of the estrous cycle. In contrast, the
      labeling intensity of glycoconjugates which contain N-acetylglucosamine as
      terminal sugar residues reached its maximum around the time of ovulation, i.e.,
      at proestrus. Glycoconjugates which carry fucose and mannose as terminal sugar
      residues appeared to be totally absent from the secretory granules of the
      oviductal ampulla during the estrous cycle. Together, electron microscopic
      observations combined with quantitative results indicate that N-acetyl-D
      galactosamine-, D-galactose-, and sialic acid-associated glycoconjugates may be
      secreted into the ampullary lumen irrespective of the stage of the estrous cycle,
      whereas the secretion of certain N-acetylglucosamine-associated glycoconjugates
      is stage specific and reaches its peak at the time of ovulation. These findings
      suggest that, at the time of ovulation, the ampullary epithelium changes its
      secretory activity and contributes its secretory products to the zona pellucida
      of oocytes freshly released from the ovary.

PMID- 9930881
TI  - Characterisation of endothelin-1-related protein in human adrenal cortex and in
      cortical lesions.
AB  - Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and
      vasoconstrictive properties. Biochemical studies suggest that this peptide occurs
      in the adrenal cortex, where it appears to influence steroid hormone production
      and catecholamine release. Concomitant with our previous immunohistological
      study, we found ET-1 immunoreactive (IR) cells in human adrenal cortex and
      cortical neoplasms, but not in the medulla. These ET-1 IR cells were numerous in
      adenomas, but were seen only occasionally in some of the carcinomas. In the
      present study, the ET-1 IR protein was extracted from normal (n = 5) and
      hyperplastic (n=3) human cortex as well as from cortical adenomas (n = 10) and
      carcinomas (n = 5). Its molecular weight, determined by SDS-polyacrylamide gel
      electrophoresis and immunoblotting, was 9 kD, which is lower than that of prepro
      ET-1 (21 kD), but larger than that of pre-ET-1 (4.3 kD) and ET-1 (2.5 kD). The
      normal cortical specimens, hyperplasias, adenomas and three of the five
      carcinomas all contained this distinct band. The two carcinomas lacking it were
      associated with Conn's syndrome. The protein may constitute a protein not
      previously described, but further studies are needed to determine its complete
      structure.

PMID- 9930882
TI  - Immunohistochemical localization of laminin, nidogen, and type IV collagen during
      the early development of human liver.
AB  - There is evidence that basement membrane components control differentiation of
      liver sinusoids and bile ducts. These processes occur in humans in the 9th
      gestational week (GW). Distribution of laminin, nidogen, and type IV collagen was
      studied during human liver development between the 6th and the 10th GW. Laminin
      and nidogen lined intrahepatic microvessels in the 6th and 7th GW decreasing in
      quantity at the beginning of the fetal period (9th-10th GW). Type IV collagen was
      detected in microvessels only from the 9th GW onward. In the early periportal
      matrix (9th-10th GW) laminin, nidogen, and type IV collagen were diffusely
      distributed. At these stages, basement membrane zones of larger portal vessels
      and of early bile ducts were also stained for all three glycoproteins. These
      results show that laminin and nidogen are localized in microvessels during early
      human liver development and decrease in concentration at the developmental stage
      during which microvessels become discontinuous. In contrast, type IV collagen is
      not present in early microvessels but occurs when laminin and nidogen disappear.
      The three glycoproteins occur together only in those areas of the developing
      liver in which, from the 9th GW onward, the differentiation of immature liver
      cells into biliary epithelium takes place.

PMID- 9930883
TI  - Co-localization of synaptophysin with different neuroendocrine hormones in the
      human gastrointestinal tract.
AB  - Colocalisation of synaptophysin has been studied in different neuroendocrine cell
      types in histologically normal mucosa from human gastrointestinal tract (corpus,
      antrum, duodenum, ileum and colon) using double-immunofluorescence stainings.
      Numerous synaptophysin immunoreactive cells were seen in the antrum, while a
      smaller number were found in the intestinal tract. Synaptophysin immunoreactivity
      was strong in the antrum but weak in the intestine. In the intestinal
      colocalisation studies the synaptophysin immunoreactivity was enhanced by using
      the tyramide amplification method. Synaptophysin and chromogranin A were
      colocalised but the latter occurred mainly basally, whereas synaptophysin was
      found to occur diffusely throughout the cytoplasm. Synaptophysin immunoreactivity
      occurred in the serotonin cells throughout the gastrointestinal tract, and in the
      antral gastrin and somatostatin cells. In the intestinal tract only a small
      fraction of somatostatin, gastrin, cholecystokinin, enteroglucagon,
      enteroglucagon/ peptide tyrosine tyrosine displayed synaptophysin
      immunoreactivity. In the gastrointestinal tract (except the antrum), chromogranin
      A is a better general neuroendocrine marker than synaptophysin. The functional
      role of synaptophysin is unclear but it may be involved in the intracellular
      transport and release of hormones. Based on the distribution background of
      synaptophysin, it seems to be of greater importance in the antrum than in the
      intestinal tract as a whole.

PMID- 9930884
TI  - Carbonic anhydrase II and H+ -ATPase in osteoclasts of four osteopetrotic
      mutations in the rat.
AB  - Osteopetrosis in laboratory animals is a metabolic bone disease characterized by
      increased skeletal mass. It is inherited as an autosomal recessive and results
      from a defect in the development and/or function of osteoclasts. We studied two
      enzymes essential for bone resorption, carbonic anhydrase II isoenzyme (CA II)
      and H+ -ATPase, in osteoclasts from four osteopetrotic mutations in the rat;
      namely incisors-absent (ia), osteopetrosis (op), toothless (tl), and
      microphthalmia (mib), to test the hypothesis that reduced bone resorption in one
      or more of these mutations results from defects in the synthesis or activity of
      one of these enzymes. CA II was present in most osteoclasts from normal, tl, op,
      and mib littermates and was homogeneously distributed in cytoplasm. CA II
      staining in ia osteoclasts was more variable and less intense than in the other
      mutations. H+-ATPase was also present in osteoclasts from normal animals and
      mutants and immunostaining showed clear polarization to the ruffled border region
      in all normal rats and mutants except ia, which showed diffuse distribution of
      staining in the cytoplasm. H+-ATPase activity (proton transport) in a related
      tissue, kidney, was normal in tl and ia rats but increased in op and mib rats
      compared to their normal littermates. These results suggest that the osteoclasts
      in osteopetrotic rat mutations are not abnormal with respect to the distribution
      of CA II and H+ -ATPase and that the function of these enzymes in the skeleton,
      while likely normal, needs to be tested directly in bone.

PMID- 9930885
TI  - Immunohistochemical investigations on the differentiation marker protein E11 in
      rat calvaria, calvaria cell culture and the osteoblastic cell line ROS 17/2.8.
AB  - Until now, many extracellular matrix proteins, e.g. osteopontin and osteonectin,
      have been used to determine a cell's osteogenic maturation. The disadvantage in
      evaluation of these proteins is their relative wide-ranging appearance throughout
      the osteogenic differentiation process. Thus, the aim of this study was to
      establish an immunohistochemical setup using E11, a marker that binds selectively
      to cells of the late osteogenic cell lineage. In addition, the histochemical
      expression of the bone matrix proteins osteonectin, osteopontin and fibronectin
      was compared to that of E11 using monoclonal antibodies. For light microscopical
      detection of osteogenic markers in cultured cells we developed a simple paraffin
      technique using a fibrin glue as embedding medium. This allows the handling of
      cultured cells such as a tissue sample and includes the use of stored biological
      specimens for further immunohistochemical experiments. We used newborn rat
      calvariae for whole tissue preparations and for isolation and cultivation of bone
      cells. In addition, we included the rat osteosarcoma cell line ROS 17/2.8 in this
      study. For the first time, we have localised E11 in osteocytes of rat calvaria
      preparations at the electron microscopical level. E11 was detected at plasma
      membranes of osteocytes and their processes, but not at those of osteoblasts.
      Accompanying experiments with cultured newborn rat calvaria cells and ROS 17/2.8
      cells revealed E11 reactivity on a subset of cells. The results obtained confirm
      the suitability of the differentiation marker E11 as a sensitive instrument for
      the characterisation of bone cell culture systems.

PMID- 9930886
TI  - Membrane structure of caveolae and isolated caveolin-rich vesicles.
AB  - Caveolae are specialized invaginated domains of the plasma membrane. Using freeze
      fracture electron microscopy, the shape of caveolae and the distribution of
      intramembrane particles (integral membrane proteins) were analyzed. The caveolar
      membrane is highly curved and forms flask-like invaginations with a diameter of
      80-120 nm with an open porus of 30-50 nm in diameter. The fracture faces of
      caveolar membranes are nearly free of intramembrane particles. Protein particles
      in a circular arrangement surrounding the caveolar opening were found on plasma
      membrane fracture faces. For isolation of caveolin-enriched membrane vesicles,
      the method of Triton X-100 solubilization, as well as a detergent-free isolation
      method, was used. The caveolin-rich vesicles had an average size of between 100
      and 200 nm. No striated coat could be detected on the surface of isolated
      caveolin-rich vesicles. Areas of clustered intramembrane particles were found
      frequently on membrane fracture faces of caveolin-rich vesicles. The shape of
      these membrane protein clusters is often ring-like with a diameter of 30-50 nm.
      Membrane openings were found to be present in the caveolin-rich membrane
      vesicles, mostly localized in the areas of the clustered membrane proteins.
      Immunogold labeling of caveolin showed that the protein is a component within the
      membrane protein clusters and is not randomly distributed on the membrane of
      caveolin-rich vesicles.

PMID- 9930887
TI  - Localizing estradiol and other diffusible hormones and drugs by autoradiography
      and immunocytochemistry.

PMID- 9930888
TI  - Human astrocytic brain tumors express AP02L/TRAIL.
AB  - AP02 ligand (APO2L) is a CD95 ligand (CD95L)-related cytokine of the tumor
      necrosis factor family that interacts with agonistic (DR4, DR5) and antagonistic
      (DcR1, DcR2) receptors. Cultured malignant glioma cells preferentially express
      agonistic receptors and are susceptible to APO2L-induced apoptosis. Here, we
      report that 8 of 8 human glioma cell lines expressed APO2L mRNA and protein in
      vitro. Immunohistochemistry using a monoclonal antibody to APO2L revealed that
      all 23 primary astrocytic brain tumors analyzed, including low-grade astrocytomas
      and glioblastomas, express APO2L in vivo. With the exception of reactive
      astrocytes, non-neoplastic glia and neurons in the cerebrum lacked
      immunoreactivity of APO2L. Thus, in addition to the CD95/CD95L system, a second
      death ligand/death receptor pair may regulate susceptibility to apoptosis in
      human glial neoplasms.

PMID- 9930890
TI  - Immunohistochemical analysis of spinal cord lesions in amyotrophic lateral
      sclerosis using microtubule-associated protein 2 (MAP2) antibodies.
AB  - We have studied microtubule-associated protein 2 (MAP2) expression in anterior
      horn neurons in the cervical and lumbar spinal cords of 19 cases of adult-onset
      sporadic amyotrophic lateral sclerosis (ALS) using immunohistochemistry.
      Specimens from 7 patients without neurological disease served as controls. MAP2
      expression decreased in the anterior gray horn of all ALS cases and in the
      intermediate gray of several ALS cases. Such reduction correlated with the degree
      of degeneration or neuronal loss in anterior horn cells and with the clinical
      symptoms of limb weakness. Cytopathologically, the MAP2 immunoreactivity
      decreased corresponding to the occurrence of individual signs of neuronal
      degeneration, such as chromatolytic neurons, shrunken neurons and pigmented
      neurons. MAP2 expression was relatively well preserved in the specimens in which
      spheroids are conspicuous. The findings of this study demonstrate MAP2 to be an
      excellent marker for the detection and quantification of anterior horn
      degeneration in ALS.

PMID- 9930889
TI  - Nuclear DNA fragmentation in Creutzfeldt-Jakob disease: does a mere positive in
      situ nuclear end-labeling indicate apoptosis?
AB  - The method of in situ end-labeling of nuclear DNA fragmentation was used in the
      study of ten patients (two biopsies, eight autopsies) with sporadic Creutzfeldt
      Jakob disease (CJD). All the patients had the typical morphological lesions
      including neuron loss, spongiform change and astrocytosis. Four of them also
      showed prion protein (PrP) deposits in the cerebral cortex, and two of them kuru
      like plaques in the cerebellum. A few cells with DNA breaks were found in the two
      biopsy cases; one of them, suffering from a panencephalopathic form of the
      disease, showed positive nuclei not only in the cerebral cortex but also in the
      subcortical white matter. Variable numbers of positive nuclei were observed in
      the gray and white matter in the eight autopsy cases, in which, although the
      distribution of positive cells roughly correlated with the distribution of neuron
      loss, no clear relationship was found as regards the distribution and degree of
      cell labeling and the degree of neuron loss. Furthermore, large numbers of
      positive cells were concentrated in a particular area, whereas a few cells were
      seen in a neighboring equally affected area. Positive glial cells in the
      plexiform layer of the CA1 area of the hippocampus, and in the frontal white
      matter were frequently encountered. Staining of the cytoplasm in a minority of
      cells was interpreted as the result of nuclear DNA leakage. None of the stained
      cells had the typical morphology of apoptosis; most particularly, peripheral
      chromatin condensation and formation of apoptotic bodies were not seen in any
      case. PrP deposits did not result in an increase of nuclear DNA breaks either
      within the area or in adjacent regions. Although positive cells were also
      observed in autopsy cases of controls which were processed in the same way,
      positive labeling as a whole was higher in CJD than in age-matched controls.
      These results show that brain nuclear DNA is vulnerable in CJD, and suggest that
      increased DNA vulnerability has a role in cell death and neuron loss. Since
      nuclear shrinkage and positive nuclear staining with the method of in situ end
      labeling of nuclear DNA fragmentation are not exclusive to apoptosis, further
      information is needed to categorize cell death in CJD as apoptosis. Necrosis or
      other forms of cell death, as well as increased DNA vulnerability to agonal
      changes of the individuals, and to postmortem delay in the fixation of the
      tissues, may account for additional positive staining in cases examined at
      autopsy.

PMID- 9930891
TI  - Immunoelectron microscopic study of c-Fos, c-Jun and heat shock protein after
      transient cerebral ischemia in gerbils.
AB  - The neuroprotective role of the expression of heat shock protein (HSP) and
      immediate early gene remains unclear. Using immunoelectron microscopy, we
      examined the ultrastructural integrity of the neurons with expression of c-Fos, c
      Jun and HSP70 in gerbils after transient cerebral ischemia and reperfusion.
      Induction of c-Fos and c-Jun was observed in the CA3 region resistant to
      ischemia, while HSP70 was expressed not only in the CA3 but also in the
      vulnerable CAI region. With immunoelectron microscopy, the expression of c-Fos/c
      Jun and HSP70 was observed in the neurons which retained neuronal integrity
      except for mitochondrial swelling and polyribosomal disaggregation. In contrast,
      the CAI neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and
      parallel stacking of rough endoplasmic reticulum, the features associated with
      the process of delayed neuronal death. These findings suggested that c-Fos and c
      Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up
      regulated even in neurons with irreversible damage, but was more preferentially
      and intensely expressed in neurons with reversible damage.

PMID- 9930892
TI  - An increase of hippocampal calretinin-immunoreactive neurons correlates with
      early febrile seizures in temporal lobe epilepsy.
AB  - Numerous studies indicate that initial precipitating injuries (IPI) such as
      febrile seizures during early childhood may play a pivotal role in the
      pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS).
      Previous data demonstrate an increase of horizontally oriented neurons in
      molecular layers of hippocampal subfields, which are immunoreactive for
      calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are
      transiently expressed in the murine developing hippocampus and are critically
      involved in neuronal pattern formation. Here we investigated a potential
      relationship between the distribution of horizontally oriented calretinin
      immunoreactive neurons and the clinical history of TLE patients with AHS.
      Horizontally oriented neurons in the molecular layer of the hippocampal formation
      have been visualized by antibodies against the calcium-binding proteins
      calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients
      with AHS were compared with autopsy specimens from developing and adult normal
      human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked
      perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML)
      followed by a gradual postnatal decline. In hippocampal specimens from TLE
      patients with AHS and seizure onset before the age of 4 years, significantly
      higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were
      encountered than in AHS patients without precipitating seizures or with an
      uneventful early medical history. However, all three groups had higher levels of
      CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In
      addition, AHS specimens showed increased CR-ir neuropil staining throughout the
      DG-ML compared with the restricted distribution of CR-ir fibers within the
      superficial granule cell layer visible in controls. These findings suggest that a
      considerable number of TLE patients with AHS display signs of impaired
      hippocampal maturation and circuitry formation as indicated by increased numbers
      of Cajal-Retzius like cells. It remains to be elucidated, how these changes
      contribute to the pathogenesis of TLE.

PMID- 9930893
TI  - Immunocytochemical demonstration of oncocytes in normal adenohypophysis.
AB  - Immunocytochemical examination for mitochondrial protein and cytochrome oxidase
      was performed to demonstrate oncocytes in normal adenohypophysis obtained from 28
      patients of various age. A small number of solitary large epithelial cells showed
      intense cytoplasmic granular immunoreactivities for mitochondrial protein and
      cytochrome oxidase. The proportions of the cells positive for the former and the
      latter ranged from 0% to 5.9% (mean+/-SD; 1.5+/-1.7%) and from 0% to 4.9% (1.4+/
      1.6%), respectively. These cells were either absent or extremely rare in young
      patients (under 10 years) but tended to increase in number with age (P < 0.0001).
      On the other hand, the mirror section technique showed that most of these cells
      were negative for adenohypophysial hormones, but a few of them were faintly
      positive for: alpha-subunit (8.0%), beta-subunits of follicle-stimulating hormone
      (4.8%), luteinizing hormone (2.5%), thyroid-stimulating hormone (1.0%), and
      growth hormone (0.5%), and were negative for prolactin and adrenocorticotropic
      hormone. We considered that these cells represent oncocytes that exist in varying
      numbers in normal adenohypophysis. It was suggested that oncocytes in normal
      adenohypophysis share various common features with tumorous oncocytes of
      pituitary oncocytomas.

PMID- 9930894
TI  - Early T cell response in the central nervous system in canine distemper virus
      infection.
AB  - The initial demyelinating lesions in canine distemper virus (CDV) infection
      develop during a period of severe immunosuppression in the absence of
      inflammation. In vitro and in vivo studies suggest that early demyelination is
      due to directly virus-induced oligodendroglial changes. In the present
      spatiotemporal study in experimentally CDV-infected dogs we observed diffuse up
      regulation of T cells throughout the central nervous system (CNS) and T cell
      invasion in early demyelinating lesions. Invasion of T cells in the CNS occurred
      despite severe immunosuppression and without any perivascular cuffing. However,
      the major fraction of invading T cells correlated with sites of viral replication
      and coincided with the demonstration of an early immune response against the
      nucleocapsid protein of CDV. Activation of microglial cells was thought to have
      elicited the migration of T cells to the CNS by secretion of chemokines: marked
      IL-8 activity was found in the CSF of dogs with acute lesions. In areas of early
      demyelination, large numbers of CD3+ cells accumulated in the tissue in the
      absence of any morphological sign of inflammation. Whether the T cells at lesion
      sites contribute to the development of acute demyelination remains uncertain at
      this stage. Antiviral cytotoxicity was not apparent since viral clearance in
      demyelinating lesions is only effective when B cells and concurring antiviral
      antibody production appeared in the subacute and chronic inflammatory stage of
      the disease. CD3+ cells appear to persist for several weeks after infection since
      they were also found in recovered dogs that did not develop demyelination.
      Accumulation of immune cells, including a significant proportion of resting T
      cells (CD45RA+) in the CNS in the early stages of the disease may facilitate the
      later development of the intrathecal immune response and associated
      immunopathological complications.

PMID- 9930895
TI  - Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and
      biochemical features of human classical Tay-Sachs disease (type B GM2
      gangliosidosis).
AB  - Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of
      depression, ataxia, circling and visual deficits were studied. Cerebrospinal
      fluid analyses revealed vacuolated macrophages that contained long parallel
      needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies
      throughout the brain, ganglion cells within the retina and neurons in the
      myenteric plexuses were variably swollen and had pale granular to finely
      vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with
      sudan black and Luxolfast blue stains. Within the brain there were occasional
      axonal spheroids, foci of astrogliosis and scattered microglial cells with
      abundant pale foamy cytoplasm. Electron microscopy of the brain and retina
      revealed numerous neurons and ganglion cells, respectively, with multiple
      membrane-bound structures that contained compact electron-dense membranous whorls
      and fewer parallel membranous stacks. Thin layer chromatography of total lipid
      extracts of the cerebral cortex of both cases revealed massive accumulation of
      G(M2) ganglioside. Crude kidney extracts of the two affected deer were able to
      hydrolyze 4-methylumbelliferyl beta-GlcNAc, but not 4-methylumbelliferyl beta
      GlcNAc-6-sulfate, indicating the defect of beta-hexosaminidase A. Cellogel
      electrophoresis of the kidney extracts also revealed the deficiency of beta
      hexosaminidase A in the two deer. It is concluded that these two deer had the
      biochemical lesion identical to that of human type B G(M2) gangliosidosis
      (classical Tay-Sachs disease).

PMID- 9930896
TI  - Large motor neuron involvement in Stiff-man syndrome: a qualitative and
      quantitative study.
AB  - Stiff-man syndrome (SMS) is characterized by fluctuating muscular rigidity and
      spasm. Recently, antibodies against glutamic acid decarboxylase (GAD), the enzyme
      catalyzing the synthesis of y-amino butyric acid (GABA), have been detected in
      SMS patients. An autoimmune mechanism against GAD was thus proposed for the
      suppression of GABAergic inhibitory interneurons, resulting in rigidity and
      spasm. We conducted quantitative investigations on the ventral horn of the spinal
      cord and its GAD immunoreactivity, post mortem, in a SMS patient and four
      controls. In the spinal cord of the SMS patient, we found a 70%, 33% and 27%
      reduction (P < 0.05) in the density of neurons with somal areas of 1000-1500
      microm2, 500-1000 microm2, and 0-500 microm2, respectively. The density of
      neurons with a somal area greater than 1500 microm2 was not reduced, although
      some neurons in this class showed central chromatolytic changes. The affected
      muscles exhibited neurogenic atrophy. GAD-like immunoreactivity in the spinal
      gray matter was not significantly decreased. The density of Purkinje cells, known
      to contain high amounts of GAD, was not significantly reduced. While the co
      occurrence of elevation of anti-GAD antibody in the serum and reduction in the
      density of small spinal neurons was confirmed, that of smaller alpha-motor
      neurons and gamma-motor neurons, the qualitative changes in larger alpha-motor
      neurons, and the preservation of spinal GAD-like immunoreactivity and non-spinal
      GAD-containing neurons suggest the involvement of factors other than autoimmune
      mechanisms through anti-GAD antibodies. More diverse mechanisms may be associated
      in the pathogenesis of SMS.

PMID- 9930897
TI  - Age-related changes of DNA repair and mitochondrial DNA synthesis in the mouse
      brain.
AB  - Using quantitative autoradiography, both nuclear DNA repair - measured as nuclear
      unscheduled DNA synthesis (UDS) - and mitochondrial (mt) DNA synthesis were
      evaluated in situ for several types of cells in the brains of untreated mice of
      various age. It was found that distinct types of neuronal cells showed a decline
      of both UDS and mtDNA synthesis with age, whereas - except for glial cells of the
      cerebral cortex - no glial or endothelial cells showed age-related alterations of
      UDS. Together with various data reported in the literature, these patterns of a
      cell type-specific decrease of UDS and mtDNA synthesis with age in the mouse
      brain lead to an improved understanding of the complex interrelationships between
      the molecular events associated with the phenomenon of aging as well as to a new
      idea regarding the cause of the specific distribution pattern of those cells in
      the human brain that are affected by the formation of paired helical filaments in
      Alzheimer's disease.

PMID- 9930898
TI  - A high incidence of apolipoprotein E epsilon4 allele in middle-aged non-demented
      subjects with cerebral amyloid beta protein deposits.
AB  - We examined the apolipoprotein E (ApoE) genotypes of 19 middle-aged non-demented
      subjects with cerebral amyloid beta protein (Abeta) deposits, and compared the
      results with those of 16 patients with sporadic Alzheimer's disease (AD) and
      those of 34 age-matched controls. The frequency of the ApoE epsilon4 allele was
      higher (P = 0.0256) in these 19 subjects (0.211) than in controls (0.059), and
      was close to that in AD patients (0.281). This result suggests that middle-aged
      non-demented subjects with cerebral Abeta deposits are at high risk of developing
      AD, and that the diffuse Abeta deposits in these cases represent an early stage
      of AD pathology. We speculate that in the majority of late-onset sporadic AD
      patients, cerebral Abeta deposition commences when these patients are in their
      forties or fifties, and that the pathological process progresses gradually,
      taking 20 to 30 years for clinical manifestation of dementia.

PMID- 9930899
TI  - On the occurrence of neuronal sprouting in the frontal cortex of a patient with
      Down's syndrome.
AB  - We report on the autopsy of a 52-year-old Down's syndrome patient with a 9-year
      history of progressive dementia. Histologically, there was a marked neuronal loss
      in the cerebral cortices with numerous neurofibrillary tangles and senile plaques
      and congophilic angiopathy. The second cortical layer was spongy in appearance
      and the frontal and temporal white matter showed marked myelin pallor.
      Immunohistochemistry for MAP2 of the frontal and temporal cortices revealed great
      reduction in the number of large pyramidal neurons. On the other hand, a much
      stronger MAP2 immunoreactivity than that seen in the controls was observed in the
      second layer, which consisted of many small pyramidal neurons with features of
      aberrant sprouting. They were recognized in the frontal cortices but not in the
      temporal cortices, and were not immunolabeled with phosphorylated-tau nor MAP5.
      On double immunolabeling with MAP2 and beta-amyloid antibodies, these neurons
      were found to be not directly associated with the formation of senile plaques.
      Ultrastructurally, MAP2 was immunolocalized in an amorphous granular form in the
      neuronal somata and processes, and paired helical filaments were not
      immunolabeled. The observation may indicate the occurrence of a remarkable
      plastic response of small pyramidal cortical neurons in this patient with Down's
      syndrome.

PMID- 9930900
TI  - Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical
      course, neuropathology and brain lipid composition in this Gaucher disease
      variant.
AB  - Glucosylceramide lipidosis results from a defective lysosomal degradation of this
      glycolipid. Lipid degradation is controlled by two components, the enzyme beta
      glucocerebrosidase and a sphingolipid activator protein. While most Gaucher cases
      are due to mutations within the gene that codes for the lysosomal enzyme, only
      two patients have been described with normal enzyme levels and mutations in the
      gene for the sphingolipid activator protein C (sap-C). Here we present the
      detailed neurological manifestations, neuropathological findings and brain lipid
      composition in one sap-C-deficient patient. The patient was an 8-year-old boy who
      presented with transient losses of consciousness, myoclonic jerks and generalized
      seizures resistant to all antiepileptic drugs. He developed progressive
      horizontal ophthalmoplegia, pyramidal and cerebellar signs, and died at the age
      of 15.5 years. Neuropathological studies demonstrated neuronal cell loss and
      neuronophagia, massive intraneuronal lipid storage and lack of perivascular
      Gaucher cells. Electron microscopy examination showed different types of storage
      including lipofuscin granules as well as the cytosomes with parallel arrays of
      bilayers that are assumed to be formed by stored lipids. General brain lipid
      composition did not show a remarkable increase or loss of any of the major lipid
      fractions but the glucosylceramide concentration in the cortex of several
      anatomical regions showed a striking increase. Fatty acid composition of the
      ceramide moiety clearly suggests that gangliosides are the main precursors in the
      cerebral cortex, while it implies an additional and distinct source in the
      cerebellum. Studying the phenotypic consequences of mutant sphingolipid activator
      proteins is critical to a better understanding of the physiological significance
      of these proteins.

PMID- 9930901
TI  - Perineurial abnormalities in the spontaneously diabetic dog.
AB  - Structural abnormalities of the perineurium from six spontaneously diabetic dogs
      (diabetes duration 4-8 years and six control animals were quantified using
      detailed electron microscopic morphometric methods on superficial peroneal nerve
      biopsy specimens. Total perineurial sheath thickness (microm) was significantly
      increased in diabetic (8.8+/-0.6) compared to control animals (6.2+/-0.3) (P <
      0.02). This was attributed to a significant increase in the mean perineurial
      lamellar width in diabetic (0.49+/-0.03) compared to control (0.40+/-0.01) (P <
      0.04) animals. The number of lamellae also showed a non-significant increase in
      diabetic animals (7.8+/-0.4) compared to controls (6.9+/-0.13) (P < 0.06). There
      was no change in the mean interlamellar space in diabetic (0.7+/-0.05) compared
      to control (0.6+/-0.06) (P = 0.15) animals. The total interlamellar space was
      increased in diabetic (5.7+/-0.5) compared to control (4.1+/-0.36) (P < 0.04)
      animals. The perineurial cell basement membrane thickness (nm) was significantly
      increased in diabetic (126.9+/-9.8) compared to control (62.8+/-6.1) (P < 0.005)
      animals. The current study has demonstrated significant abnormalities of the
      perineurium in the spontaneously diabetic dog, which may have relevance to the
      pathogenesis of diabetic neuropathy.

PMID- 9930902
TI  - Polyglutamine aggregates: a possible component of eosinophilic intracular
      inclusions in the hippocampal pyramidal neurons of a patient with amyotrophic
      lateral sclerosis.

PMID- 9930903
TI  - Determinants of efficacy of atrial pacing in preventing atrial fibrillation
      recurrences.
AB  - INTRODUCTION: Several studies have shown that single or dual site atrial pacing
      is effective in reducing the frequency of recurrent atrial fibrillation (AF) in
      selected patients. However, it is still unclear what the best predictors are of
      long-term efficacy of atrial pacing. METHODS AND RESULTS: Forty-seven patients
      with paroxysmal AF requiring demand pacing underwent electrophysiologic study and
      dual chamber pacemaker implant. After 4 months of follow-up, patients were
      divided into two groups according to the presence (group 1) or absence (group 2)
      of symptomatic AF recurrences. Atrial pacing markedly reduced AF recurrences in
      all patients. Twenty-four patients were free of arrhythmia. The basal state
      conduction times (CTs) and the incremental conduction times (ICTs), during
      programmed electric stimulation between the high right atrium (HRA) and the
      coronary sinus ostium (CSos), but not between the HRA and the His-bundle region,
      were significantly longer in group 1. There was no statistical difference in the
      effective refractory period (ERP) recorded at the HRA, the low right atrium
      (LRA), and the CSos between the two groups, whereas the differences between the
      greatest and least recorded ERPs measured from the HRA, LRA, and CSos (deltaERP)
      were significantly greater in group 1 patients. Two parameters were selected by
      discriminant multivariate analysis, namely deltaCTos (ICT-CT between HRA and
      CSos) and deltaERP. The first had a greater relative importance in predicting AF
      recurrence (r2 = 0.33 and r2 = 0.1, respectively). CONCLUSION: Single site atrial
      pacing is effective in reducing AF recurrences, with decreasing efficacy in
      patients with greater right atrial conduction delay and wider refractoriness
      dispersion.

PMID- 9930904
TI  - Cardiac parasympathetic stimulation via QRS-synchronous low-energy shocks in
      humans.
AB  - INTRODUCTION: In patients receiving test shocks to verify lead connections at
      implantation, we anecdotally have observed postshock delay. The purpose of this
      study was to determine whether QRS-synchronous low-energy shocks delivered by
      implantable defibrillators result in postshock cycle length prolongation, and to
      determine the mechanism of this phenomenon. METHODS AND RESULTS: Twenty-five
      patients undergoing defibrillator testing were studied, three with epicardial
      patches and 22 with transvenous leads. Each patient received QRS-synchronous
      shocks of 0.2, 0.4, 0.6, and 2.0 J in random order. Patients were further
      randomized to receive either saline or 2.0 mg atropine intravenously, and then
      given a second sequence of shocks. At baseline, the postshock cycle length
      (1,035+/-245 msec) was significantly longer than the preshock cycle length (968+/
      177 msec, P = 0.01). In patients with a coronary sinus (CS) or superior vena cava
      (SVC) lead, the mean prolongation was 91+/-160 msec, compared with 12+/-106 msec
      for patients without such a lead (P < 0.0001). All energy levels resulted in
      significant postshock prolongation compared with preshock cycle lengths (P <
      0.05). Postshock prolongation before atropine was 76+/-162 msec, compared with 
      13+/-52 msec afterward (P < 0.00001). Biphasic shocks resulted in greater
      postshock prolongation than monophasic shocks of equal energy. CONCLUSION: Low
      energy shocks delivered during the QRS complex cause postshock cycle length
      prolongation in man. This effect required the presence of a CS or SVC lead.
      Atropine inhibited this effect, suggesting the phenomenon was mediated by direct
      cardiac parasympathetic nerve stimulation by the intracardiac shock.

PMID- 9930905
TI  - Catecholamine facilitated reentrant ventricular tachycardia: uncoupling of
      adenosine's antiadrenergic effects.
AB  - INTRODUCTION: Adenosine has no direct electrophysiologic function in ventricular
      tissue, but in the presence of cyclic adenosine monophosphate (cAMP), stimulation
      exerts a potent antiadrenergic effect. This effect has been exploited in the
      recognition and treatment of ventricular tachycardia (VT) due to cAMP-mediated
      triggered activity and automaticity, which are respectively terminated and
      suppressed by adenosine. However, the effects of adenosine on catecholamine
      facilitated reentrant VT are unknown. A pivotal issue is whether termination of
      VT with adenosine is mechanism specific, or whether it represents a nonspecific
      antiadrenergic effect. The purpose of this study, therefore, was to define the
      effects of adenosine in a well-characterized group of patients with catecholamine
      facilitated reentrant VT. METHODS AND RESULTS: Fourteen patients with
      catecholamine-facilitated reentry were studied. In the 12 patients with
      structural heart disease (including two with arrhythmogenic right ventricular
      dysplasia), adenosine (260 to 550 microg/kg) failed to slow or terminate VT. Two
      patients without structural heart disease had intrafascicular tachycardia
      confined to the left posterior fascicle, a calcium-dependent, verapamil-sensitive
      arrhythmia. In the absence of isoproterenol, verapamil terminated VT but
      adenosine did not. However, when isoproterenol was subsequently required for
      facilitation of tachycardia, adenosine terminated VT in both patients.
      CONCLUSION: Adenosine has no antiadrenergic (antiarrhythmic) effect in patients
      with catecholamine-facilitated VT due to structural heart disease. Patients with
      verapamil-sensitive, left posterior intrafascicular reentry have an unusual dual
      response to adenosine. In the unstimulated state, adenosine has no effect on
      basal inward calcium current and, therefore, no effect on VT. However, when
      induction of VT requires amplification of the inward calcium current through
      stimulation of cAMP, adenosine sensitivity of VT becomes manifest. These results
      indicate that with few exceptions, termination of VT with adenosine is strongly
      suggestive of a cAMP-mediated triggered mechanism rather than reentry.

PMID- 9930906
TI  - Bezold-Jarisch-like reflex during radiofrequency ablation of the pulmonary vein
      tissues in patients with paroxysmal focal atrial fibrillation.
AB  - INTRODUCTION: Information is lacking about the occurrence of ablation-related
      proarrhythmic events during application of radiofrequency (RF) energy at the
      pulmonary veins in patients with paroxysmal focal atrial fibrillation. The
      purpose of this study was to assess the theoretical risk of reflex bradycardia
      and hypotension response during RF ablation of these regions rich in endocardial
      nerve terminals. METHODS AND RESULTS: Among the 40 consecutive patients (29 men,
      11 women; mean age 65+/-12 years) with clinically documented frequent attacks of
      paroxysmal atrial fibrillation who underwent superior pulmonary vein ablation for
      left focal atrial fibrillation, 6 patients (15%) developed bradycardia
      hypotension syndrome during energy delivery. A single atrial fibrillation trigger
      focus in the left or right superior pulmonary vein was found in 3 and 1 patients,
      respectively. Two patients had two trigger foci originating from the orifice or
      proximal part of both superior pulmonary veins. After RF current was applied for
      a period of 14+/-10 seconds, 2 patients developed junctional rhythm and sinus
      bradycardia, another 2 patients had profound sinus bradycardia, 1 patient had two
      episodes of sudden onset of complete AV block with resultant 9.5-second asystole,
      and 1 patient showed profound sinus bradycardia, transient AV block, and an 8
      second asystole due to sinus arrest. Blood pressure fell when any substantial
      bradyarrhythmias occurred. All 6 patients were free of rhythm disturbances during
      the postablation follow-up period (mean 8+/-2 months). CONCLUSION: RF catheter
      ablation of the pulmonary vein tissues could evoke a variety of profound
      bradycardia-hypotension responses. The Bezold-Jarisch-like reflex might be the
      underlying mechanism.

PMID- 9930907
TI  - Preexcitation secondary to fasciculoventricular pathways in children: a report of
      three cases.
AB  - INTRODUCTION: Fasciculoventricular connections are the rarest form of accessory
      pathways leading to preexcitation. Electrophysiologic characteristics of these
      pathways include ventricular preexcitation with normal PR and AH intervals and
      short HV intervals during sinus rhythm. In addition, atrial overdrive pacing
      prolongs the PR interval without affecting the HV interval or the degree of
      preexcitation. METHODS AND RESULTS: From March 1994 through February 1997, 3 of
      59 pediatric patients referred for electrophysiologic study for preexcitation on
      surface ECGs were found to have fasciculoventricular pathways. Two patients had
      no inducible supraventricular tachycardia. One patient had successful ablation of
      both a left lateral pathway and a concealed anterolateral pathway that had
      facilitated antidromic and orthodromic supraventricular tachycardias,
      respectively. CONCLUSION: Children often manifest minimal preexcitation via
      accessory AV pathways due to rapid AV conduction and/or left lateral pathway
      location. Fasciculoventricular pathways may masquerade as Wolff-Parkinson-White
      syndrome. Separation of the two diagnoses depends on the demonstration of
      specific electrophysiologic criteria.

PMID- 9930908
TI  - Clinical value of the postpacing interval for mapping of ventricular tachycardia
      in patients with prior myocardial infarction.
AB  - INTRODUCTION: The postpacing interval (PPI) has been used to discriminate
      bystander sites from critical sites within a ventricular tachycardia (VT) reentry
      circuit, with a PPI that is similar to the VT cycle length (CL) being indicative
      of a site within the reentry circuit. The purpose of this study was to assess the
      clinical value of the PPI for identifying effective target sites for ablation of
      VT at sites of concealed entrainment in patients with prior myocardial
      infarction. METHODS AND RESULTS: In 24 patients with coronary artery disease and
      a past history of myocardial infarction, 36 VTs with a mean CL of 483+/-80 msec
      (+/- SD) were mapped and targeted for radiofrequency (RF) ablation. The only
      criterion used to select target sites for ablation was concealed entrainment. In
      a post hoc analysis, the PPI was measured at 47 ineffective and 26 effective
      ablation sites. The mean PPI-VTCL difference at the 26 effective sites (114+/-137
      msec) did not differ significantly from the mean at the 47 ineffective sites
      (177+/-161 msec; P = 0.1). The sensitivity of a PPI-VTCL difference < or = 30
      msec for identifying an effective ablation site was 46%, the specificity 64%, the
      positive predictive value 41%, and the negative predictive value 68%. CONCLUSION:
      The PPI-VTCL difference is not useful for discriminating between sites of
      concealed entrainment that are within or outside of a VT reentry circuit in
      patients with prior infarction. Therefore, in patients with prior infarction, the
      PPI is not clinically useful for identifying sites of concealed entrainment at
      which RF ablation should or should not be attempted.

PMID- 9930909
TI  - Is the postpacing interval of any value during ablation of postinfarction
      ventricular tachycardia?

PMID- 9930910
TI  - Junctional tachycardia during radiofrequency ablation of the slow pathway in
      patients with AV nodal reentrant tachycardia: effects of autonomic blockade.
AB  - INTRODUCTION: The autonomic nervous system richly innervates the peri-AV nodal
      region and may be activated during radiofrequency (RF) ablation for AV nodal
      reentrant tachycardia, resulting in the generation of junctional tachycardia. The
      purpose of this prospective study was to determine the role of the autonomic
      nervous system in the genesis of junctional tachycardia. METHODS AND RESULTS: We
      compared the characteristics of junctional tachycardia in patients with (n = 10)
      and without (n = 10) autonomic blockade undergoing RF ablation for AV nodal
      reentrant tachycardia. Intravenous administration of atropine (0.04 mg/kg) and
      propranolol (0.2 mg/kg) were used to block the autonomic nervous system. There
      were no differences in clinical variables and baseline electrophysiologic
      characteristics between the two groups except for slightly longer effective
      refractory periods of the fast pathway and of the atrium in the autonomic
      blockade group. The autonomic blockade shortened the baseline sinus cycle length
      and effective refractory period of the ventricle only but not other
      electrophysiologic characteristics of the AV node. The junctional tachycardia was
      observed during ablation in each patient, but its occurrence and cycle length, as
      well as numbers of consecutive junctional beats, were not altered by the
      autonomic blockade. CONCLUSION: Our results indicate that the muscarinic and beta
      adrenergic components of the autonomic nervous system play no role in the genesis
      of junctional tachycardia.

PMID- 9930911
TI  - Differing rate dependence and temporal distribution of repolarization alternans
      in patients with and without ventricular tachycardia.
AB  - INTRODUCTION: Repolarization alternans (RPA) may reflect repolarization
      heterogeneities underlying VT, yet its temporal dynamics are poorly understood.
      We hypothesized that RPA occurring late, rather than early, within repolarization
      reflects a temporal variation in recovery that may predispose to wavefront
      fractionation and the initiation of reentrant VT, and that this temporal
      distribution may vary with heart rate. METHODS AND RESULTS: ECG leads I, aVF, and
      V1 were recorded in 40 patients during electrophysiologic study. RPA across the
      JT interval was computed spectrally for 64-beat sequences at paced cycle lengths
      (CLs) of 600, 500, and 400 msec, and expressed as the T wave alternans ratio
      (TWAR) on the vector ECG lead. Significant RPA (TWAR > or = 3) was reconstructed
      into the time domain, and its center of area used to represent its temporal
      distribution. Twenty-two patients were inducible into VT and 18 were not. RPA was
      of larger magnitude in inducible than noninducible patients (TWAR = 11.1 vs 4.42,
      P = 0.035; 38.3 vs 5.74, P = 0.004; and 88.8 vs 4.28, P = 0.001 in each,
      respectively), and was distributed later (P < 0.02; CL 600 msec). Applying TWAR >
      or = 3 to the distal half of the JT segment produced greater specificity for
      inducible VT (88.9%, 66.7%, and 69.2% at each CL, respectively) than did RPA of
      the entire JT segment (77.8%, 53.3%, and 69.2%). CONCLUSION: RPA is more specific
      for inducible VT when distributed late rather than elsewhere in repolarization,
      and this temporal distribution is heart rate sensitive. Further study is required
      to interpret these findings in the context of temporal dispersion of
      refractoriness.

PMID- 9930912
TI  - Microwave ablation of myocardial tissue: the effect of element design, tissue
      coupling, blood flow, power, and duration of exposure on lesion size.
AB  - INTRODUCTION: The biophysical properties of microwave electromagnetic radiation
      suggest that it may be an alternative to radiofrequency (RF) energy for ablation
      of arrhythmias resistant to treatment using RF ablation. METHODS AND RESULTS: The
      aim of this study was to characterize lesions produced using simple element
      designs in a blood superfused ovine tissue model to simulate endocardial
      ablation. The effect of tissue bath flow, duration of microwave exposure, and
      changes in forward power on lesion size were examined using a modified monopole
      element. Lesion size increased with increasing duration of exposure and
      increasing forward power (P < 0.05). Lesion depth was 0.7+/-0.7 mm after 30
      seconds and 11.5+/-1.9 mm after 360 seconds. Lesion depths at 61, 71, and 80 W
      were 6.4+/-3.7, 8.9+/-2.0, and 11.9+/-1.2 mm, respectively. Altering flow within
      the bath from 3 to 5 L/min did not significantly change lesion size. CONCLUSION:
      Simple element designs can be used to produce a range of lesions from very small
      sizes to lesions that are transmural in the ventricle. The temperature half-time
      for microwave ablation is far greater than that of RF ablation. Like RF lesions,
      the lesions produced by microwave ablation have greater width than depth. Deep
      penetration of lesions into the ventricular myocardium can only be achieved with
      these elements by producing lesions of perhaps unnecessarily large volume.

PMID- 9930913
TI  - Heterogeneous loss of connexin43 protein in ischemic dog hearts.
AB  - INTRODUCTION: Ischemia causes cell decoupling in the myocardium. Prolonged
      ischemia activates proteases and causes degradation of structural proteins as
      well as gap junctions. There is little information about the degradation of gap
      junction protein during the early time period after acute ischemia. The purpose
      of the present study was to investigate connexin43 (Cx43) protein degradation and
      distribution patterns in the canine left ventricular wall during 1 to 6 hours of
      ischemia. METHODS AND RESULTS: Ischemia of canine left ventricular myocardium was
      induced by ligation of the left anterior descending coronary artery. Following a
      period of in situ ischemia of up to 6 hours, samples were harvested, and standard
      paraffin slides were prepared for Cx43 and wheat germ agglutinin double labeling.
      Cx43 distribution was visualized by confocal microscopy. In controls, homogeneous
      distribution of Cx43 staining was determined. Ischemia caused a loss of Cx43 with
      a heterogeneous pattern by mixing foci of infarcted cells among normal cardiac
      myocytes. To determine if the changes were induced by heterogeneous reduction in
      the blood supply, an in vitro ischemic model was studied to induce more
      homogeneous ischemia. Western blot analysis of these in vitro ischemic tissue
      samples revealed a reduction of Cx43 protein concentration with a 50% decay time
      of 4.8 hours. Cx43 dephosphorylation was detected after 1 hour of in vitro
      ischemia. Heterogeneous loss of Cx43 was found in the in vitro ischemic tissue.
      There were no significant changes in Cx43 staining density during the first hour
      of ischemia at a time when dephosphorylation of the protein was observed. After 1
      hour of ischemia, Cx43 was reduced at intercalated disk areas, and, after 6
      hours, most Cx43 disappeared at intercalated disk areas, while small amounts of
      Cx43 remained at side-to-side junctions. CONCLUSION: Cx43 undergoes both
      distribution and concentration changes following acute cardiac ischemia. The loss
      of Cx43 protein is heterogeneous. Cx43 dephosphorylation occurred within 1 hour
      following ischemia.

PMID- 9930914
TI  - Field stimulation of isolated chick heart cells: comparison of experimental and
      theoretical activation thresholds.
AB  - INTRODUCTION: This study examines the accuracy of using membrane models to
      predict activation thresholds for chick heart cells during field stimulation.
      METHODS AND RESULTS: Activation thresholds were measured experimentally in ten
      embryonic chick heart cells at 37 degrees C for stimulus durations 0.2 to 40
      msec. Activation was assessed by observing the mechanical twitch of the cell. The
      heart cells ranged in diameter from 15.0 to 26.7 microm. Since the electric field
      required for activation depends on diameter, the thresholds were expressed as the
      maximum field-induced transmembrane potential, Vth = 1.5 a Eth, where a is the
      cell radius and Eth is the strength of the electric field at threshold. A cell
      model was created using a singular perturbation method and membrane models
      describing the ionic currents of a heart cell. The study used membrane models of
      Ebihara and Johnson (1980), Luo and Rudy (1991), Shrier and Clay (1994), and
      their combinations. The results show that for stimuli longer than 1 msec,
      theoretical activation thresholds were within one standard deviation of
      experimental thresholds. For shorter stimuli, the models failed to predict
      thresholds because of a premature deactivation of the sodium current. The
      modification of the m gates dynamics, so that they closed with a time constant of
      1.4 msec, allowed to predict thresholds for all durations. The root mean square
      error between experimental and theoretical thresholds was 6.14%. CONCLUSIONS: The
      existing membrane models can predict thresholds for field stimulation only for
      stimuli longer than 1 msec. For shorter stimuli, the models need a more accurate
      representation of the sodium tail current.

PMID- 9930915
TI  - Two-to-one AV block associated with the congenital long QT syndrome.
AB  - INTRODUCTION: Conduction abnormalities associated with long QT syndrome (LQTS)
      have been reported as "pseudo 2:1 AV block" due to sinus intervals shorter than
      ventricular refractoriness. METHOD AND RESULTS: We report the electrophysiologic
      characteristics of a patient suffering from congenital LQTS with episodes of true
      2:1 AV block. Induction of 2:1 infra-Hisian blocks and return to 1:1 conduction
      were observed using single atrial and ventricular extrastimuli. The block was
      located in the Purkinje network but not in the myocardium. CONCLUSION: The His
      Purkinje system of our LQTS patient displayed dynamic properties with a strong
      increase in refractoriness for short-long sequences and a decrease for long-short
      sequences that triggered intermittent 2:1 AV blocks.

PMID- 9930916
TI  - Clinical profile of commotio cordis: an under appreciated cause of sudden death
      in the young during sports and other activities.
AB  - Not particularly well recognized are athletic field catastrophes in which
      virtually instantaneous cardiac arrest is produced by nonpenetrating chest blows
      in the absence of heart disease or identifiable morphologic injury to the chest
      wall or heart (commotio cordis). To better characterize the clinical profile of
      this syndrome, we have assembled 70 cases, including 34 occurring during
      organized competitive athletics and 36 others that occurred during informal
      recreational sports at home, school or the playground, or during nonsporting
      activities. Ages were 2 to 38 (mean age: 12) with 70% < 16 years old. Most common
      sports involved were youth baseball (n = 40), softball (n = 7), and ice hockey (n
      = 7). Seven (10%) of the 70 commotio cordis victims, including six with
      documented ventricular fibrillation, have survived the consequences of their
      chest blow. Eleven of the events (16%) occurred despite the presence of chest
      padding believed to be potentially protective. Four victims experienced modest
      chest blows while in circumstances completely unrelated to sports activities;
      three of the four individuals who delivered these blows were ultimately convicted
      of criminal acts within the justice system. An experimental model of low-energy
      chest wall impact demonstrates that commotio cordis events are due largely to the
      exquisite timing of blows during a narrow window within the repolarization phase
      of the cardiac cycle, 15 to 30 msec prior to the peak of the T wave.

PMID- 9930917
TI  - Long-short RR intervals and the right bundle branch.

PMID- 9930918
TI  - Spontaneous inversion of an implanted defibrillator.

PMID- 9930919
TI  - A shocking state of affairs.

PMID- 9930920
TI  - Computational aspects of expression data.
AB  - Several experimental techniques are available nowadays to study the spectrum of
      genes expressed in a cell at a specific moment. Typically, such methods generate
      large amounts of expression data that may be hard to interpret. Here we review
      computational questions and approaches resulting from the various experimental
      techniques.

PMID- 9930921
TI  - Monoclonal antibody to tumor necrosis factor-alpha modulates hepatocellular Ca2+
      homeostasis during hemorrhagic shock in the rat.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of shock-induced
      cellular and humoral inflammatory cascades. The present study investigated the
      role of TNF-alpha in oxidative membrane injury and altered hepatocyte Ca2+
      regulation, both of which are critical steps in cellular dysfunction during
      ischemia/reperfusion events. Hemorrhagic shock was induced by bleeding male
      Sprague-Dawley rats (200-250 g, n=6/group) to a mean arterial blood pressure of
      40 mmHg for 60 min. Rats were resuscitated with 60% of shed blood and twice the
      shed blood volume as Ringers' lactate. At the end of hemorrhage and 60 min after
      resuscitation, hepatocytes were isolated by liver collagenase perfusion.
      Hepatocyte Ca2+ uptake (Ca2+up) and Ca2+ membrane flux (Ca2+flux) were determined
      by 45Ca2+ incubation techniques. Hepatocyte reduced/oxidized glutathione and
      lipid peroxidation were determined fluorometrically. Both hemorrhage and
      hemorrhage/resuscitation significantly increased hepatocyte Ca2+up and Ca2+flux.
      The monoclonal chimeric mouse gamma1 TNF-alpha antibody (TN3gamma1.19.12; 20
      mg/kg b.w.) given with resuscitation significantly decreased hepatocyte Ca2+up
      and Ca2+flux and prevented hepatocyte lipid peroxidation. These findings suggest
      that oxidative membrane injury could be the result of TNF-alpha modulation of
      hepatocellular Ca2+ regulation during hemorrhage/resuscitation.

PMID- 9930922
TI  - Purified soluble guanylyl cyclase expressed in a baculovirus/Sf9 system:
      stimulation by YC-1, nitric oxide, and carbon monoxide.
AB  - Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide, a messenger
      molecule with multiple clinical implications. Understanding the activation of sGC
      is an important step for establishing new therapeutic principles. We have now
      overexpressed sGC in a baculovirus/Sf9 system optimized for high protein yields
      to facilitate spectral and kinetic studies of the activation mechanisms of this
      enzyme. It was expressed in a batch fermenter using a defined mixture of viruses
      encoding the alpha and beta1 subunits of the rat lung enzyme. The expressed
      enzyme was purified from the cytosolic fraction by anion exchange chromatography,
      hydroxyapatite chromatography, and size exclusion chromatography. By use of this
      new method 2.5 l culture yielded about 1 mg of apparently homogeneous sGC with a
      content of about one heme per heterodimer without the need of a heme
      reconstitution step. The enzyme did not contain stoichiometric amounts of copper.
      The basal activities of the purified enzyme were 153 and 1259 nmol min(-1) mg(-1)
      in the presence of Mg2+ and Mn2+, respectively. The nitric oxide releasing agent
      2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO) stimulated the enzyme 160-fold
      with Mg2+, whereas the NO-independent activator 3-(5'-hydroxymethyl-2'-furyl)-1
      benzylindazole (YC-1) induced an increase in the activity of 101-fold at a
      concentration of 300 microM. The combination of DEA/NO (10 microM) and YC-1 (100
      microM) elicited a dose-dependent synergistic stimulation with a maximum of a 792
      fold increase over the basal activity in the presence of Mg2+, resulting in a
      specific activity of 121 micromol min(-1) mg(-1). The synergistic stimulation of
      DEA/NO and YC-1 was attenuated by the sGC inhibitor 1H-(1,2,4)oxadiazole(4,3
      a)quinoxalin-1-one (ODQ) (10 microM) by 94%. In a different experimental setup a
      saturated carbon monoxide solution in the absence of ambient oxygen or NO
      stimulated the enzyme 15-fold in the absence and 1260-fold in the presence of YC
      1 compared to an argon control. The heme spectra of the enzyme showed a shift of
      the Soret peak from 432 to 399 and 424 nm in the presence of DEA/NO or carbon
      monoxide, respectively. The heme spectra were not affected by YC-1 in the absence
      or in the presence of DEA/NO or of carbon monoxide, which reflects the fact that
      YC-1 does not interact directly with the heme group of the enzyme. In summary,
      this study shows that our expression/purification procedure is suitable for
      producing large amounts of highly pure sGC which contains one heme per
      heterodimer without a reconstitution step. The activator experiments show that in
      a synergistic stimulation with YC-1 sGC can be activated maximally both by nitric
      oxide and by carbon monoxide and that YC-1 does not directly act via heme. The
      described method should help to facilitate the investigation of the new
      therapeutic principle of NO-independent guanylyl cyclase activators.

PMID- 9930923
TI  - The early history of endocrine cell transplantation.

PMID- 9930924
TI  - Melatonin in relation to the antioxidative defense and immune systems: possible
      implications for cell and organ transplantation.
AB  - Melatonin, a molecule synthesized and secreted by the mammalian (including human)
      pineal gland, has a variety of seemingly unrelated functions in organisms. In
      photoperiodically-dependent seasonal breeders, the changing melatonin signal
      imparts seasonal information to the species thereby regulating the annual cycle
      of reproduction Melatonin also is involved in a number of 24 h rhythms and is
      believed to be an important component of the circadian system. More recently,
      melatonin was found to relate to immune function in organisms and to be an
      effective antioxidant. As an antioxidant melatonin would appear to provide
      substantial protection against free radicals which are generated under a variety
      of experimental corrections, including ischemia/reperfusion injury. These latter
      two functions of melatonin, i.e., as an immune system modulator and as an
      antioxidant, both may have applicability to cell and organ transplantation.

PMID- 9930925
TI  - Strategies of protection from nitric oxide toxicity in islet inflammation.
AB  - Nitric oxide is thought to contribute to beta cell destruction during islet
      inflammation in animal models of type I diabetes. In vitro, inhibition of
      inducible nitric oxide synthase protects islet cells from the damaging effects of
      inflammatory cells or cytokines. However, the administration of several inducible
      nitric oxide synthase inhibitors to prediabetic animals had variable effects on
      disease progression. An alternative approach is to prevent the lethal
      consequences of nitric oxide action at the level of islet cells. We observed that
      the suppression of poly-(ADP-ribose)-polymerase ensures survival of islet cells
      exposed to nitric oxide. Cells could also be rendered resistant by the induction
      of endogenous stress proteins in particular of heat shock protein 70. Nitric
      oxide is not only a strong cytotoxic agent, but is also able to modulate immune
      reactions by interfering with Th1/Th2 reactivities. This may occur via induction
      of the interleukin-12 antagonist IL-12(p40)2. Development of type 1 diabetes is
      known to be correlated with a shift from a Th2 status during benign insulitis to
      a Th1 status during destructive insulitis. This shift was found dependent on
      local interleukin-12 gene expression. Indeed, administration of a natural
      interleukin-12 antagonist suppressed the progression of islet inflammation and
      concomitant upregulation of the inducible nitric oxide synthase.

PMID- 9930926
TI  - Glutamic acid decarboxylase antibodies are more frequent than islet cell
      antibodies in islet transplanted IDDM patients and persist or occur despite
      immunosuppression.
AB  - Pancreatic islet grafts transplanted into patients with autoimmune diabetes are
      potentially threatened by two immune responses, allograft rejection and the
      recurrence of autoimmune insulitis. In the present study we investigated the
      humoral autoimmune response directed to islet autoantigens by studying islet cell
      antibodies and glutamic acid decarboxylase (GAD 65) antibodies in twenty-one
      insulin-dependent diabetes-mellitus (IDDM) patients undergoing intraportal islet
      allotransplantation. Islet transplantation was performed according to the
      following recipient categories: Islet after kidney transplantation (n=10),
      simultaneous islet and kidney transplantation (n=6) and islet transplant alone
      (n=5). GAD 65 antibodies were detected in a radioligand GAD 65 antibody assay
      using recombinant, in vitro translated, human 35S-methionin labelled GAD 65 as
      tracer. Islet cell antibodies were determined by indirect immunofluorescence
      technique on human pancreas. In six out of twenty-one patients we observed GAD 65
      antibodies before islet transplantation and the GAD 65 antibodies persisted
      despite immunosuppression. In contrast only two subjects were concordantly islet
      cell antibody positive and the titre decreased post transplantation. In addition
      we observed occurrence of GAD 65 antibodies in five subjects that were shown to
      be antibody negative before islet transplantation with three of them subsequently
      becoming positive for islet cell antibodies. The remaining ten patients were GAD
      65 antibody and islet cell antibody negative before islet transplantation and
      remained negative thereafter. Interestingly none of the patients was exclusively
      positive for islet cell antibodies without being positive for GAD 65 antibodies.
      In summary we have demonstrated in twenty-one islet grafted individuals that
      humoral autoimmunity to islet antigens can persist or occur despite
      immunosuppression. Islet cell antibodies appear to be less frequent (5 out of 21,
      23%) compared to GAD 65 antibodies (11 out of 21, 52%) suggesting that they are
      more affected by immunosuppressive therapy. We conclude that GAD 65 antibodies
      are a useful tool to further evaluate a possible link between persistent
      autoimmunity and early or late graft failure after islet transplantation.

PMID- 9930927
TI  - Metabolic strategies to predict and improve intrahepatic islet graft function.
AB  - The success rate of intraportal islet grafts and the length of graft survival
      have been low and variable in diabetic humans. Goal of this work was to outline
      the principal strategies to predict and improve islet graft. The study of 15
      insulin dependent diabetic patients after islet and kidney transplantation
      allowed us to build a metabolic database. The patients received an hyperglycemic
      clamp to assess insulin secretion and a euglycemic clamp in combination with
      tracers of glucose, amino acid and lipid metabolism and indirect calorimetry to
      assess insulin action. The results of this initial study were used to design new
      metabolic strategies to predict and improve islet graft function. Special
      emphasis is given to the importance of developing and studying the metabolic
      phenotype of transgenic animals with the knock out or the overexpression of genes
      involved in specific metabolic pathways.

PMID- 9930928
TI  - Insulitis and mechanisms of disease resistance: studies in an animal model of
      insulin dependent diabetes mellitus.
AB  - Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease characterised
      by extreme insulin deficiency due to an overall decrease in the mass of properly
      functioning beta-cells. This reduction occurs as a result of insulitis. the
      outcome of which will depend upon the intensity of the cytotoxic attack and the
      ability of beta-cells to resist and repair immune mediated cell damage. To
      further elucidate the relationship between the insulitis process and beta-cell
      defence and repair mechanisms in the prevention of diabetes we have studied a
      unique subgroup of diabetes prone (DP) BB/S rats which have demonstrated an
      ability to recover from IDDM (BB/S-R). Animals were diagnosed as diabetic at 115
      days of age, subsequently receiving insulin therapy (1.49+/-0.1 IU/day) for a
      total of 19.7 days during 1 to 4 episodes of IDDM. Following a prolonged symptom
      free period of 90 days, an IPGTT revealed that BB/S-R rats possessed normal
      glycaemic control. Islets were isolated from the BB/S-R rats and their glucose
      stimulated insulin response was shown to be comparable to Wistar control islets.
      Furthermore, control and BB/S-R islets showed both a similar structural integrity
      and insulin content. BB/S-R islets cultured for 24 hr in IL-1beta (10(-13) M)
      maintained a significant insulin secretory response to glucose in contrast to
      Wistar controls in which the response was completely inhibited. Nitrite
      production was induced by IL-1beta, in a dose-dependent manner, in control islets
      whereas there was no significant increase in production in the islets of BB/S-R
      rats. These findings suggest that previous immune directed beta-cell attack may
      induce a state of increased resistance to subsequent deleterious effects of
      cytokine-mediated cytotoxicity. Overall therefore, the present study shows how
      the "recovered" BB/S-R rat model provides a unique opportunity to assess the
      direct effects of insulitis on pancreatic islets and how this interaction may
      subsequently determine disease outcome.

PMID- 9930929
TI  - Beta cell proliferation and growth factors.
AB  - Formation of new beta cells can take place by two pathways: replication of
      already differentiated beta cells or neogenesis from putative islet stem cells.
      Under physiological conditions both processes are most pronounced during the
      fetal and neonatal development of the pancreas. In adulthood little increase in
      the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia
      of the beta cells is observed both in rodents and man. Increased mitotic activity
      has been seen both in vivo and in vitro in islets exposed to placental lactogen
      (PL), prolactin (PRL) and growth hormone (GH). Receptors for both GH and PRL are
      expressed in islet cells and are upregulated during pregnancy. By mutational
      analysis we have identified different functional domains of the cytoplasmic part
      of the GH receptor. Thus the mitotic signaling only requires the membrane
      proximal part of the receptor and activation of the tyrosine kinase JAK2 and the
      transcription factors STAT1 and 3. The activation of the insulin gene however
      also requires the distal part of the receptor and activation of calcium uptake
      and STAT5. In order to identify putative autocrine growth factors or targets for
      growth factors we have cloned a novel GH/PRL stimulated rat islet gene product,
      Pref-1 (preadipocyte factor-1). This protein contains six EGF-like motifs and may
      play a role both in embryonic pancreas differentiation and in beta cell growth
      and function. In summary, the increasing knowledge about the mechanisms involved
      in beta cell differentiation and proliferation may lead to new ways of forming
      beta cells for treatment of diabetes in man.

PMID- 9930930
TI  - CD44 splice variants in draining lymph nodes precede allograft rejection of
      endocrine cells.
AB  - Upon allogeneic transplantation (Tx) of pancreatic islets under the kidney
      capsule of diabetic rats, cells from draining lymph nodes and, to a minor degree,
      bone marrow transiently upregulate CD44 splice variants as detected by RT-PCR
      using CD44 variant exon specific primers. Maximal expression was on day 5 post Tx
      in lymph nodes and thus precedes islet rejection sufficiently (in this model by 5
      days) to still permit establishing rescue by immunosuppressive therapy. CD44
      variant exon sequence could therefore serve as early markers of allograft
      rejection.

PMID- 9930931
TI  - Transplantation of human fetal pancreas: fresh vs. cultured fetal islets or ICCS.
AB  - The paucity of human adult islets available for transplantation in IDDM makes the
      use of human fetal pancreas a potential alternative. Fetal pancreatic endocrine
      cells grow and differentiate over time when fresh explants or cultured islet-like
      cell clusters (ICCs) are transplanted under the kidney capsule in athymic nude
      mice. We have recently developed a procedure to isolate fetal islets, which
      differ from ICCs in their beta-cell content. This study was undertaken to compare
      the maturation and growth of grafts from purified fetal islets, containing mostly
      beta-cells, to grafts of mostly undifferentiated endocrine cell precursors,
      cultured as ICCs, and fresh, uncultured tissue. Total insulin content was highest
      in the fresh tissue pre-transplant while insulin levels fell precipitously during
      culture as either fetal islets or ICCs. Although 500 fetal islets contained more
      insulin than 500 ICCS before transplantation, the insulin content of the
      resulting grafts was the same 3 months post-transplantation. The degree of
      stimulation following glucose challenge was comparable, as was the histological
      appearance. However 70 mg of fresh tissue was needed to generate the fetal islets
      while only 30 mg was needed for the ICCs. Grafts of 30 mg fresh tissue also had
      similar total insulin contents and stimulation following glucose challenge, but,
      when normalized to DNA there was a significantly higher concentration of insulin
      in the grafts from ICCs or fetal islets. Moreover there were distinct
      morphological differences, with fibrous and ductal elements prominent in the
      grafts from fresh tissue, which were also much larger and more diffuse, with
      cystic elements evident macroscopically. Quantitative immunohistochemical
      analysis showed that grafts from cultured tissue were 48.3+/-5% positive for
      immunoreactive insulin compared with grafts from fresh tissue which were only
      13.3+/-1.4% positive for insulin. In conclusion cultured ICCs, a heterogeneous
      mixture of hormone-containing and undifferentiated endocrine cells, are a
      preferable source for transplantation than either purified fetal islets or
      uncultured tissue.

PMID- 9930932
TI  - Cyclic ADP-ribose-mediated insulin secretion and Reg, regenerating gene.
AB  - Glucose is the primary stimulus of insulin secretion in pancreatic beta-cells of
      the islets of Langerhans. CD38 has both ADP-ribosyl cyclase, which catalyzes the
      formation of cyclic ADP-ribose from NAD+, and cyclic ADP-ribose hydrolase, which
      converts cyclic ADP-ribose to ADP-ribose. ATP, produced by glucose metabolism,
      inhibits the cyclic ADP-ribose hydrolase of CD38 and therefore causes cyclic ADP
      ribose accumulation in beta-cells. Then, cyclic ADP-ribose acts as a second
      messenger for Ca2+ mobilization from the endoplasmic reticulum to secrete
      insulin. The mechanism of insulin secretion as described above is completely
      different from the conventional hypothesis in which Ca2+ influx from
      extracellular sources was assumed to play a role in insulin secretion by glucose.
      On the other hand, strategies for influencing the replication of islet beta-cells
      and the growth of the beta-cell mass may be more important for ameliorating
      diabetes. Reg, regenerating gene, is involved in the growth of the beta-cell
      mass, and Reg protein has been shown to increase the beta-cell mass in a 90%
      depancreatized diabetic rat model, thereby ameliorating the diabetes. CD38 is
      involved in the formation of cyclic ADP-ribose and is essential for the glucose
      sensitivity of beta-cells for insulin secretion. Therefore, CD38 gene and Reg
      gene will become targets for genetic engineering for diabetic beta-cells.

PMID- 9930933
TI  - An investigation into the distribution of different collagen types within adult
      and juvenile porcine pancreata.
AB  - One of the difficulties of porcine islet isolation is their fragility during
      collagenase digestion. The object of this study was to determine the distribution
      of 4 different collagen types within adult and juvenile porcine pancreata. Five
      different areas from each pancreas were analysed by light microscopy. The
      distribution of collagen types I, IV, V and VI were measured within the
      interlobar, intralobular (acinar), peri-insular and intra-islet regions. Their
      was an abundance of collagen type VI compared to I, IV and V in both the
      interlobar and intralobular septa in both juveniles (P<0.001) and adults
      (P<0.001). The periinsular collagen content also showed diversity. This was
      mainly attributable to the distribution of collagen type I (weak) and type VI
      (intense) in both adults and juveniles. In general, the peri-insular capsule was
      fragmentary and contained less than 50% of the total islet circumference. The
      latter finding taken together with the distributions of different collagen types
      can partly explain some of the variability of porcine islet isolation.

PMID- 9930934
TI  - The influence of collagenase solvent on the isolation of islets from 5 week old
      pigs: a comparison of TCM-199 and UW.
AB  - Islet transplantation is a potential treatment for diabetes, but the techniques
      for islet isolation are inefficient and the recovery rates for isolated islets
      are often low. As the solutions employed during the isolation process may affect
      islet yield, we have investigated the effect of collagenase solvent, and compared
      the effect of dissolving collagenase in TCM-199 (TCM) or University of Wisconsin
      (UW) solution on yield and viability of islets isolated from 5 week old pigs.
      Pancreata were transported to the laboratory in UW solution, and the islets
      isolated using a manual method of collagenase digestion. The optimum
      concentration of collagenase which would liberate the maximum number of islets
      was determined for each solvent, and then the yield and viability of islets
      isolated using collagenase in TCM and UW were compared. It was found that, when
      UW was used as collagenase solvent, a higher concentration of collagenase was
      required to liberate the maximum number of islets. Comparative experiments
      revealed that although the total number of isolated islets was greater using UW
      as the solvent, the number of islet equivalents was similar in both preparations.
      More than 90% of the cells in both preparations excluded trypan blue, although
      according to a scoring system, preparations isolated using UW showed greater
      viability. The stimulation indices in response to glucose and theophylline were
      similar for both preparations, but islets isolated using UW generally responded
      with a lower but more sustained insulin release. In conclusion, there was no
      difference between the total amount of islet tissue isolated using TCM or UW as
      solvent for collagenase. The preparations isolated using UW were more fragmented,
      but exhibited superior viability.

PMID- 9930935
TI  - Evidence for a significant correlation of donor pancreas morphology and the yield
      of isolated purified human islets.
AB  - In clinical islet transplantation to patients with type 1 diabetes mellitus, the
      number of isolated and purified islet has been identified as a key determinant
      for functional success of the islet graft. With improved isolation methods based
      on the original procedure published by Ricordi et al. yield and function of
      isolated islets were considerably enhanced. However, there is still a large
      variance in the number, purity, viability and secretory capacity of islets
      isolated from brain-dead human donor pancreata, significantly hampering
      utilization of human islet preparations derived from a single donor for one
      diabetic recipient. The reasons for the limited success in islet isolation and
      purification have not been clarified in detail yet. Recent studies have
      indicated, that donor preconditions, and a number of technical factors during
      organ procurement and the islet isolation process itself are critical to
      successful islet isolation. This study aimed at identifying distinct
      morphological and histopathological characteristics of the donor pancreas as
      determinants for the outcome of human islet isolation and purification.

PMID- 9930936
TI  - Glucose sensitivity of porcine and human islets in vitro.
AB  - Preliminary experiments about the suitability of different commonly used culture
      media in our laboratory indicated, that prolonged exposure to high glucose
      concentrations during low temperature culture (LTC) impairs the viability of long
      term cultured human islets. As a consequence of the heterogeneity of tested media
      the present study was aimed to evaluate the influence of different glucose
      concentrations on survival, viability and in-vitro function of cultured human
      islets in order to optimize islet survival until transplantation and to compare
      species dependent differences in glucose sensitivity. Quantified aliquots of
      freshly isolated (digestion-filtration, ficoll gradient purification) islets from
      consecutively processed human (n=6) and porcine (n=11) pancreata were subjected
      to different glucose concentrations (human islets: 500, 750, 1000 and 2000 mg/l;
      porcine islets: 1000 and 2000 mg/l) in CMRL (22 degrees C) for 8-10 days. After
      LTC survival, viability and glucose-stimulated insulin release of incubated
      tissue was assessed. A reduction of glucose concentration promotes survival and
      viability of human islets but impairs in vitro function at the same time,
      presumably due to a reduced glucose oxidation as expressed by the significantly
      reduced stimulation index. In contrast to these findings in the human, elevated
      glucose concentration in porcine islet culture increases survival but reduces the
      glucose-stimulated insulin release and the viability of cultured islets. The
      contradiction of the results in regard to islet survival related to islet
      viability are still unclear in the pig and needs further evaluation.

PMID- 9930937
TI  - Large variability of the intracellular ATP content of human islets isolated from
      different donors.
AB  - Observations in experimental heart, liver, kidney and pancreas transplantation
      indicated that graft function and survival correlates significantly with ATP
      content of transplanted tissue. The ATP content of cells can be reduced by
      several factors i.e. the nutritional donor status, storage technique, warm
      ischemia and cold ischemia time. This study investigates the intracellular ATP
      content of isolated human islets for the first time. Quantified samples of
      freshly isolated (digestion-filtration, continuous ficoll gradient purification)
      and cultured (22 degrees C, CMRL+10% FCS) islet equivalents (IEQ) of
      consecutively processed human pancreata from multiorgan donors (UW vascular
      flush) were shock frozen in liquid nitrogen and stored at -196 degrees C until
      rapid thawing, sonification and subsequent luminometric determination of ATP
      (Luciferin-Luciferase-reaction) and assessment of islet protein (IP). The ATP
      content was analysed for freshly isolated and subsequently 5+/-1 days cultured
      islets (n=10). The ATP content of freshly isolated human islets was 130.4+/-53.4
      pg/microg IP (mean+/-SEM) corresponding to 20.7+/-6.3 pg/IEQ. After culture ATP
      content increased to 265.5+/-113.3 pg/microg IP (204.2+/-41.5%) corresponding to
      43.7+/-15.3 pg/IEQ (216.1+/-34.9%; p<0.05). The coefficient of variation was
      129.5%, 96.5% (fresh) and 135.0%, 111.0% (cultured) for ATP/microg IP and
      ATP/IEQ, respectively. The present data show that: (1) the ATP content of freshly
      isolated human islets varies enormously; (2) intraislet ATP levels increase
      significantly during 22 degrees C culture suggesting that the capacity to produce
      ATP is maintained despite hypothermic environment. More data are necessary to
      clarify the relevance of intraislet ATP content for graft function and survival
      after islet transplantation.

PMID- 9930938
TI  - Insulin resistance and impaired insulin secretion due to phosphofructo-1-kinase
      deficiency in humans.
AB  - The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is usually
      explained as a combination of peripheral insulin resistance and impaired beta
      cell function. Phosphofructo-1-kinase (PFK1) is a rate limiting enzyme in
      glycolysis, and its muscle subtype (PFK1-M) deficiency leads to an autosomal
      recessively inherited disorder known as glycogenosis type VII or Tarui's disease.
      It was evaluated whether PFK1-M deficiency leads to NIDDM in humans. A core
      family of four was evaluated for PFK1-M deficiency by DNA- and enzyme-activity
      analyses. All members underwent oral and intravenous glucose tolerance test
      (oGTT/ivgtt), as well as an insulin sensitivity test (IST) using octreotide.
      RESULTS: Father (46 years, BMI 22.4 kg/m2) and older son (19 years, BMI 17.8
      kg/m5) showed homozygous PFK1-M deficiency, while mother (47 years, BMI 28.4
      kg/m5) and younger son (13 years, BMI 16.5 kg/m5) were shown to be heterozygously
      PFK1-M-deficient on enzyme activity levels. DNA analysis revealed an exon 5
      missense-mutation at one allele of all four members, and an exon 22-frameshift
      mutation at the other allele of the two homozygously affected individuals. By
      oGTT the father showed impaired glucose tolerance, and the mother clinical
      diabetes. By ivGTT both parents and the older son had a decreased first phase
      insulin secretion, and a diminished glucose disappearance rate. The IST showed
      marked insulin resistance in both parents and the older son, and moderate
      resistance in the younger son, previously not described. CONCLUSION: PFK1-M
      deficiency leads to a metabolic state typical for early NIDDM in homozygously
      affected humans, especially concerning insulin resistance and loss of first phase
      beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in
      a subgroup of patients.

PMID- 9930940
TI  - Increased glucagon-stimulated insulin secretion of cryopreserved rat islets
      transplanted into nude mice.
AB  - Cryopreservation is the only available technique for long-term storage of
      pancreatic islets. The freezing/thawing protocol may cause considerable loss of
      viable islet tissue and impair its function in vivo. The aim of this study was to
      investigate glucose and insulin levels after transplantation of fresh and
      cryo/thawed rat islets. Rat pancreatic islets were isolated following intraductal
      collagenase injection and Ficoll gradient purification. After isolation, islets
      were cultured for 24 h and then either transplanted or frozen after stepwise
      addition of DMSO according to Rajotte et al. and stored in liquid nitrogen. After
      rapid thawing islets were stepwise transferred into RPMI medium and cultured for
      another 24 h. The recipients were athymic mice with streptozotocine-induced
      diabetes. Two hundred fresh (n=13) or cryo/thawed (n=15) islets were transplanted
      beneath the renal capsule. Glucose levels were measured for 14 days and blood
      samples for insulin determination were obtained 15 min after i.p. glucagon (10
      mg/kg) administration on day 14. Glucose levels were normalized (<9 mmol/l) in
      all recipients within 3 days since transplantation. On day 14, mean fasting
      values+/-SE in fresh and cryo/thawed islet groups were 4.0+/-0.6 and 4.4+/-0.4
      mmol/l, respectively (P>0.05). Fasting insulin levels were higher in the
      cryo/thaw than in the fresh islet group (1.67+/-0.33 vs 0.57+/-0.13 ng/ml;
      P<0.01). Post-glucagon levels did not differ significantly (1.45+/-0.24 vs 0.86+/
      0.24 ng/ml; P=0.06). While glucagon significantly increased insulin levels
      (P<0.01) in the fresh islet group, no change in insulin levels was observed
      (P>0.05) in the cryo/thaw group. Immunohistochemical staining demonstrated
      fragmentation of viable islet tissue which was more apparent in the cryo/thaw
      group. We conclude that in a short-term study cryo/thawed rat islets produce
      higher insulin levels than fresh islets transplanted into nude mice. This may be
      due to better islet survival or loss of feed-back regulation.

PMID- 9930939
TI  - The relative contribution of insulin secretory capacity, insulin action, and
      incretins to metabolic control after islet transplantation in dogs.
AB  - Adequate metabolic control is central to the concept of islet transplantation,
      but has received limited attention. We studied metabolic control in 8 dogs at 6-9
      months after intrasplenic autografting of approximately 25% of the normal mass
      islets--as compared to 30 controls. A similar posttransplant reduction to
      approximately 25% of the insulin secretory capacity as assessed by intravenous
      arginine stimulation during 35 mM glucose clamps, mirrored the reduction of the
      islet mass. Postprandially, in contrast, the insulin response had increased to
      140% in the islet recipients--with a concomitant rise of glycemia to
      approximately 8.5 mM. Posttransplant, the insulin secretory capacity correlated
      both with the index of insulin action (which averaged 55% of the normal value) as
      assessed by euglycemic hyperinsulinemic clamps, and--inverse--with the
      postprandial glucose excursions. Because insulin action did not correlate with
      postprandial glucose, the insulin secretory capacity appears to be the primary
      determinant of the impaired glucose tolerance. Marked postprandial
      hyperglucagonemia, and a virtually absent pancreatic polypeptide response in the
      grafted animals, may also have contributed to the impaired glucose tolerance.
      Posttransplant, infusion of a physiological dose of the gut hormone glucagon-like
      peptide-1 during 8.5 mM glucose clamps--mimicking the postprandial glycemia-
      potentiated glucose-stimulated insulin 175%. Thus, after transplantation of a
      suboptimal islet mass, postprandial glucose excursions are restrained by
      hyperglycemic potentiation of the entero-insular axis, which may account for the
      difference in the insulin response to the intravenous and oral challenges.
      Because, the insulin secretory capacity reflects the islet mass and appears to be
      the major determinant of glucoregulation, transplantation of a larger islet mass
      may allow near-normal glycemic control.

PMID- 9930941
TI  - Effects of cyclosporine A on the process of vascularization of freely
      transplanted islets of Langerhans.
AB  - We studied in vivo the effect of cyclosporine A (CsA) on both pancreatic islet
      vascularization and microvascular perfusion using intravital fluorescence
      microscopy and the dorsal skinfold chamber model in Syrian golden hamsters.
      Syngeneic transplantation was performed in order to exclude allograft- or
      xenograft-induced microvascular alterations. To study the effect of CsA on islet
      angiogenesis and vascularization, animals received 20 mg/kg CsA daily from day 0
      until day 14 after transplantation (group A). To study toxic effects of CsA on
      islet microcirculation, the grafts were allowed to vascularize without
      immunosuppression, and 20 mg/kg CsA was given daily from day 10 until day 20
      after transplantation (group B). Quantitative analysis of the process of islet
      vascularization in group A revealed a functional capillary density (FCD) of
      515.6+/-72.7 cm(-1) at day 6 after transplantation without further increase until
      day 14 (504.3+/-16.7 cm(-1)). Islet transplants which were not treated with CsA
      during the process of angiogenesis/vascularization (group B) demonstrated a
      slightly but significantly (P<0.05) higher FCD (604.7+/-42.5 cm(-1)) at day 14
      after transplantation, indicating slightly improved vascularization when compared
      to transplants of group A. Additional CsA treatment of these islet grafts until
      day 20 did not induce derangements of microvascular perfusion (601.2+/-67.0 cm(
      1)), indicating that the immunosuppressive, drug has no toxic/detrimental effects
      on the transplants nutritional blood supply. We conclude that CsA only slightly
      alters the process of final vascularization of freely transplanted islets, and
      does not deteriorate nutritive perfusion of completely vascularized grafts.

PMID- 9930943
TI  - Endotoxin-mediated activation of cytokine production in human PBMCs by
      collagenase and Ficoll.
AB  - Endotoxin-induced early inflammatory reactions may inhibit the function and
      survival of isolated cells or cell aggregates after transplantation. By the
      chromogenic Limulus amebocyte lysate assay we found rather high but variable
      endotoxin concentrations in the chemicals used for islet isolation, i.e.
      collagenase and Ficoll. Liberase, a special collagenase preparation from
      Boehringer, was nearly endotoxin-free. Correlating to the endotoxin content,
      collagenase and Ficoll had the capacity to induce interleukin-1beta release from
      human peripheral blood mononuclear cells. Because collagenase and density
      gradient media are needed in most cell isolation procedures from solid organs,
      each lot of these chemicals should be tested for endotoxin contamination. In
      pancreatic islet transplantation, the use of endotoxin-free chemicals may
      diminish early local inflammatory reactions at the graft site and thereby reduce
      the number of islets needed for successful islet transplantation.

PMID- 9930942
TI  - Cytokine mRNA expression in peripheral blood cells of immunosuppressed human
      islet transplant recipients.
AB  - The macrophage derived cytokines interleukin-beta (IL-1beta), and tumor necrosis
      factor alpha (TNFalpha), and the T-cell derived cytokine interferon gamma
      (IFNgamma) have been implicated to play an important role in early attack on
      islet cells during human islet transplantation (ITx). Therefore, the aim of this
      study was to investigate the influence of the current immunosuppressive induction
      therapy in clinical islet transplantation on mRNA expression of these cytokines
      in blood cells, compared to lipopolysaccharide (LPS) induced cytokine release in
      vitro and to plasma levels. The cytokine release correlated to lymphocyte counts
      and significantly decreased after ATG, and partially recovered 2 weeks after ITx.
      Unexpectedly, there was no correlation between mRNA expression for IL-1beta in
      total blood and the number of lymphocytes and monocytes remaining after anti
      thymocyte globulin (ATG)-therapy. Even when the blood was nearly totally depleted
      from mononuclear cells, high amounts of IL-1beta mRNA could be detected. However,
      IL-1beta secretion could not be stimulated in vitro. Our results show that
      application of ATG during ITx might contribute to graft survival during the early
      posttransplant period by suppression of the synthesis of monocyte derived
      cytokines IL-1beta and TNFalpha.

PMID- 9930944
TI  - Oxygen radical production in human mononuclear blood cells is not suppressed by
      drugs used in clinical islet transplantation.
AB  - Inflammatory islet damage mediated by cytokines and oxygen radicals may limit the
      success of clinical islet transplantation for treatment of insulin-dependent
      diabetes mellitus. In this study, we investigated whether drugs such as currently
      used in islet-transplanted patients inhibit the release of IL-1beta, TNFalpha,
      and superoxide from mononuclear blood cells in vitro. Methylprednisolone (10
      microg/ml) inhibited the release of IL-1beta and TNFalpha, but had no effect on
      superoxide generation. Both pentoxifylline (66 microg/ml) and cyclosporin A (300
      ng/ml) slightly inhibited TNFalpha release without affecting IL-1beta or
      superoxide generation. Nicotinamide (0.25 mM) did not interfere with the
      generation TNFalpha or superoxide and only slightly inhibited IL-1beta
      production. A combination of methylprednisolone, pentoxifylline, cyclosporin A,
      and nicotinamide (concentrations for each substance as described above) inhibited
      TNFalpha generation by 74+/-6% (mean value+/-SEM, mononuclear blood cells from
      seven diabetic patients) without affecting IL-1beta or superoxide generation.
      These data show that standard immunosuppressive therapy in islet transplanted
      patients may partially inhibit cytokine release but does not affect the
      generation of potentially islet-toxic superoxide from mononuclear cells.

PMID- 9930945
TI  - Endotoxin impairs the engraftment of rat islets transplanted beneath the kidney
      capsule of C57BL/6-mice.
AB  - The primary objective of this investigation was to determine the effect of
      endotoxin on islet xenograft survival within the first three days after
      transplantation. Pancreatic islets from Lewis rats were prepared under endotoxin
      free conditions with Liberase (Boehringer) and purified by centrifugation on
      endotoxin-free Ficoll/Histopaque. After overnight incubation, with or without 10
      microg/ml endotoxin, the islets were transplanted beneath the kidney capsule of
      normoglycemic C57Bl/6-mice. Three days later, kidneys were removed and their
      insulin content were measured. We could demonstrate significant differences
      (P<0.01) in insulin recovery between lipopolysaccharide-free and
      lipopolysaccharide-containing grafts. In case of endotoxin contaminated islets,
      we found only 13+/-2% (n=9) of the original insulin content, in contrast to 53+/
      7% (n=9) when endotoxin-free islets where grafted. In experiments with islets
      isolated by use of conventional (lipopolysaccharide-containing) collagenase, and
      then cultured in endotoxin-free medium, insulin recovery three days after
      transplantation was 36+/-1% (n=13).

PMID- 9930946
TI  - Critical islet mass for successful porcine islet autotransplantation.
AB  - A major reason for the failure of clinical islet transplantations may be a
      limited islet mass. The aim of this study was to determine the critical islet
      mass necessary for normalization of glucose metabolism in a porcine model.
      Diabetes was induced by total pancreatectomy. The splenic lobe of the pancreas
      was intraductally distended with UW-solution containing 2.67-3.33 mg/ml
      collagenase, and the distended pancreas was digested in a continuous digestion
      filtration device. The islets were purified on a isoosmotic Ficoll-sodium
      diatrizoate gradient. The survival period of the diabetic recipients in group 2
      and 3 receiving, respectively, a low (2.14+/-0.39 microL/kg body weight) and a
      high (4.99+/-0.83 microL/kg body weight) islet mass was significantly prolonged
      compared to that of diabetic recipients in group 1 receiving no islet
      transplantation. However, the survival period of the recipients in group 2 was
      not significantly different to that in group 3. Three recipients of an islet mass
      of >5 microl/kg body weight became normoglycemic (fasting blood glucose <100
      mg/dl) for more than two months. Furthermore, the glucose and insulin release
      reactions to the glucose challenge were comparable to that before pancreatectomy.
      Contrarily, another five diabetic recipients of an islet mass of <4 microL/kg
      body weight became a fasting blood glucose level of <200 mg/dl. The glucose and
      insulin release reactions to the glucose challenge were improved only, but not
      normalized compared to that before pancreatectomy. The data presented in this
      study demonstrate that metabolic normalization in pancreatectomized diabetic
      minipigs can be established by autotransplantation of an islet mass of >5
      microl/kg body weight.

PMID- 9930947
TI  - Pancreatic islet autotransplantation combined with total pancreatectomy for the
      treatment of chronic pancreatitis--the Leicester experience.
AB  - Islet autotransplantation offers the potential for preventing the surgically
      induced diabetes that is an inevitable consequence of total pancreatectomy. This
      paper describes the first islet autotransplant programme in the United Kingdom
      and the first series in the world to use the spleen as a site for the islet
      graft. Over an 11 month period, 7 patients underwent total pancreatectomy for
      chronic pancreatitis combined with a simultaneous islet autotransplant. All 7
      patients had normal glucose-tolerance levels and normal C-peptide levels pre
      operatively. In 6 patients, islets were embolized into the liver via the portal
      vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets
      into the splenic sinusoids via a short gastric vein (median transplanted volume=4
      ml). One patient received islets into the spleen alone. One patient died of a
      stroke 4 weeks post transplantation. Two patients have achieved insulin
      independence, with a further two patients achieving "transient" insulin
      independence (<1 month). The remaining 2 patients, although requiring reduced
      insulin doses, have not achieved insulin-independence. However, all patients have
      C-peptide levels within the normal range. In trying to explain these findings,
      split proinsulin levels were measured and found to be elevated. High levels of
      split proinsulin cross react with the C-peptide assay and this would explain the
      falsely elevated C-peptide levels. Indeed insulin levels in these patients were
      all below the normal range. These findings would suggest that the use of C
      peptide levels as the "gold standard" for monitoring islet autograft function,
      may require reappraisal.

PMID- 9930948
TI  - Insulin secretory patterns and blood glucose homeostasis after islet
      allotransplantation in IDDM patients: comparison with segmental- or whole
      pancreas transplanted patients through a long term longitudinal study.
AB  - IDDM patients undergoing islet, segmental pancreas or whole pancreas
      allotransplantation were studied at regular intervals after surgery (3-6 months,
      1, 2, 3 and 4 years) to evaluate glycometabolic control (24 h metabolic profile,
      OGTT) and serum free insulin response to insulinogenic stimuli (arginine, IVGTT).
      Patients received the same immunosuppressive therapy, based on cyclosporin,
      steroids and azathioprine. Islet transplanted patients showed: 1) an early peak
      of insulin secretion after arginine, that was maintained up to 4 years; 2) an
      early, but low peak of insulin secretion after IVGTT, which was lost at 3 years,
      despite evidence that islets were still functioning (insulin independence with
      normal HbAlc levels); 3) a diabetic-like response to OGTT at 3 months, which
      improved at 2 years (IGT response); 4) fasting euglycemia with mild and
      reversible post-prandial hyperglycemia during the 24 h metabolic profile, which
      was maintained for up to 2 years. Insulin secretory patterns of islet
      transplanted patients were similar to segmental pancreas transplanted patients,
      and lower than whole pancreas transplanted patients. The reduced beta cell mass
      transplanted and the functional denervation of the transplanted islets seem to be
      the major determinants of this behaviour.

PMID- 9930949
TI  - Improved survival of intraportal pancreatic islet cell allografts in patients
      with type-1 diabetes mellitus by refined peritransplant management.

PMID- 9930950
TI  - Transplantation of islets of Langerhans in patients with insulin-requiring
      diabetes mellitus undergoing orthotopic liver transplantation--the Miami
      experience.
AB  - Most patients with cirrhosis of the liver have detectable insulin resistance. In
      60-80% of patients with cirrhosis, impaired glucose tolerance can be uncovered;
      approximately 20% of these patients eventually develop overt diabetes.
      Theoretically, insulin resistance and glucose intolerance could be improved or
      reversed by orthotopic liver transplantation alone or in association with a
      simultaneous transplant of pancreatic islet cells from the same donor. To
      investigate these possibilities we initiated a pilot study of simultaneous liver
      and pancreatic islet cell transplantation in seven patients with diabetes and
      liver cirrhosis. Donor bone marrow cells were also infused to enhance the
      acceptance of the grafts. Seven patients who received only orthotopic liver
      transplantation and donor bone marrow cells were used as historical controls. The
      preliminary results of this pilot trial suggest that islet cell transplantation
      in conjunction with orthotopic liver transplantation improves glucose metabolism
      in patients with liver cirrhosis in association with reduced insulin requirements
      and HbA1c levels. These results were evident in spite of pre- and post-transplant
      basal C-peptide levels that were unchanged. Further evaluation of the effects of
      orthotopic liver transplantation with or without islet cell transplantation will
      require a randomized prospective trial including accurate metabolic evaluation
      with the euglycemic insulin clamp technique.

PMID- 9930951
TI  - Indications for clinical islet transplantation today and in the forseeable future
      -the diabetologist's point of view.
AB  - The treatment of patients with type 1 diabetes mellitus has to focus on short
      term and long-term risks of the disease which means to avoid hyperglycemic or
      hypoglycemic coma as well as late complications. As we know from the DCCT study
      metabolic control substantially lowers the risk for retinopathy, nephropathy and
      neuropathy. We also know, that keeping the blood glucose in a nearly normal range
      inevitably is connected with a marked increase of severe hypoglycemia, an event
      which occurs more frequently when normoglycemia has been reached and the further
      slow decline of blood glucose is not recognized by the patient (autonomous
      neuropathy, hypoglycemia unawareness of other origin, long duration of diabetes
      etc.). Furthermore, counterregulatory hormones as glucagon and epinephrine may be
      lacking due to diminished or even lost alpha cells within the islets and as
      recently observed due to fibrosis of the adrenal medulla in long-term diabetes.
      The consequences of severe hypoglycemia are manifold: in the actual situation of
      unconsciousness the risk of heavy injuries and as long-term consequences
      irreversible brain damage may occur. Finally, the effort of the patient to reach
      normoglycemia includes the burden of an intensive blood glucose self-control day
      by day. This broad scenario of all the achievements and of all the problems
      connected with an intensified insulin treatment has to be regarded when the
      indication for an islet transplant will be discussed. From our point of view as
      clinicians it seems adequate not to give definite recommendations but to express
      our considerations for islet transplantation in patients with type 1 diabetes
      mellitus with the following list (table 1). It must be clearly stated, that at
      present transplantation of isolated islets by no means can serve as a treatment
      for a larger number of patients and this may hold through also for the
      foreseeable future. In this context, also the many contraindications should be
      summarized (table 2). Consequently we have to deal with several questions and
      problems which can be subdivided into those regarding the possible benefit for
      the patients from an islet graft (full success = insulin independence, partial
      success = lower exogenous insulin requirement due to additional endogenous
      insulin, measured by C-peptide levels, more stable glucose metabolism) and those
      regarding possible side effects (primary risk of implantation, threat for
      rejection of the primarily transplanted kidney). Furthermore, one may ask for
      risks when islets are transplanted alone (ITA). We therefore will address the
      following areas: 1. Simultaneous islet and kidney transplants 2. Islet
      transplants after kidney transplantation alone (IAK) 3. Islet transplantation
      after pancreas transplantation failure (P-failure) 4. Defect hypoglycemia
      counterregulation--life threatening hypoglycemia unawareness as indication for
      islet transplantation? 5. Autonomous cardiac neuropathy as indication for islet
      transplantation? 6. Significant clinical problems with exogenous insulin therapy
      as indication for islet transplantation?

PMID- 9930952
TI  - Xenoislet transplantation: experimental and clinical aspects.
AB  - Ten diabetic renal transplant patients had porcine fetal islet-like cell clusters
      (ICC) injected intraportally or placed under the kidney capsule. In some
      patients, temporary graft survival was achieved, as evidenced by the urinary
      excretion of small amounts of porcine C-peptide (4 patients) and the
      identification of some intact insulin-staining cells in a biopsy specimen (1
      patient). Glucose metabolism remained unaffected. To improve the results, better
      islets and better immunosuppressive protocols are required. We found that, while
      fetal porcine ICC produced insulin only after several weeks, adult islets gave
      immediate insulin production. The search for an optimal immunosuppression was
      conducted in the pig-to-rat islet transplant model. A clear inhibitory effect on
      the xenograft rejection was observed when using some of the new drugs. The best
      results were achieved with a triple drug regimen consisting of cyclosporine,
      mycophenolate mofetil and leflunomide.

PMID- 9930953
TI  - Fetal islet xenotransplantation in rodents and primates.
AB  - Beta cell replacement in IDDM by transplantation of either isolated adult islets
      of Langerhans or of proliferating immature islet tissue from fetal pancreas are
      potential ways of curing this disease. Because of the dearth of human cadaver
      donors adult allogeneic islets are scarce and in most Western societies
      availability of human fetal tissue of suitable maturity is also uncommon. The use
      of xenogeneic islets from domestic species already widely used for human
      consumption, e.g. pigs, could overcome this scarcity but xenogeneic tissues are
      faced with major problems of graft rejection. Hyperacute rejection (HAR) is the
      main cause of destruction of immediately vascularised xenografts and is caused by
      the interaction of natural cross-reactive antibodies with donor endothelial
      cells. Neovascularized islet grafts do not have donor EC as the target for HAR
      and are not subjected to this problem but are still acutely rejected. The
      mechanism of this destruction is still poorly understood but is clearly T cell
      dependent. However, current immunosuppression that is usually adequate for
      control of allograft rejection generally does not prevent xenograft rejection. A
      better understanding of the ways in which xenoantigens are recognised and of the
      nature of the immune response they initiate is fundamental to the development of
      appropriate strategies for the safe and effective control of xenograft rejection.
      The studies summarized herein describe the response of mice and primates to a
      challenge with fetal pig pancreas grafts. The rejection response that develops is
      different from that seen against a challenge with fetal allogeneic islets.
      Although the xenograft response is highly T cell dependent the actual effectors
      of graft damage appear to be different from those that provoke allograft
      destruction and include macrophages and granulocytes, particularly eosinophils,
      and possibly non-classical T cells.

PMID- 9930954
TI  - Factors in discordant xenograft survival.

PMID- 9930955
TI  - Animal model of experimentally induced ectopic enchondral ossification in nude
      mice with xenograft of porcine epiphyseal cartilage.
AB  - In a specific animal model the induction of heterologous enchondral ossification
      was examined in long term follow-up. Physiologically normal and devitalized
      frozen porcine epiphyseal cartilage as a control group were transplanted as s.c.
      xenograft into athymic nude mice (nu/nu). 15 weeks after transplantation the
      porcine growth plate cartilage showed the development of viable cartilage tissue
      in the recipients, further differentiating to juvenile long bone with epiphysis,
      diaphysis and growth plate. Porcine growth plate cartilage increased s.c. in the
      recipient nude mice, showing enchondral ossification without any physiological
      load, and finally an unexpected development towards complete juvenile long bone.

PMID- 9930957
TI  - Viability and recovery of frozen-thawed human islets and in vivo quality control
      by xenotransplantation.
AB  - Cryopreservation of islets of Langerhans offers advantages for the
      transplantation into diabetic patients. In this study two different methods of
      cryopreservation were compared with respect to islet viability and recovery after
      cryostorage. It was also investigated whether human islet survival in mice was
      affected by cryopreservation. Aliquots of human islets were cryopreserved
      conventionally or vitrified, respectively. After rapid thawing, islet viability
      and islet equivalent (IEQ) recovery rate were determined. Aliquots of freshly
      isolated or conventionally cryopreserved islets were transplanted beneath the
      kidney capsule of non-diabetic C57BL/6 mice. After three days renal insulin
      content was determined. Islet cell viability was 17.3+/-8.0% for vitrified and
      51.8+/-3.0% for conventionally cryopreserved islets; the recovery rate was 84.8+/
      12.2% and 92.8+/-12.4%, respectively. Insulin recovery after transplantation was
      25.6+/-7.3% for fresh and 24.1+/-7.4% for cryopreserved islets. This study
      suggests that the conventional method of cryopreservation is superior to
      vitrification with respect to islet viability after thawing. We found no
      significant difference between fresh and cryopreserved islets with respect to
      insulin recovery after transplantation into mice.

PMID- 9930956
TI  - Expression of the GALalpha(1-3)GAL epitope on pig islets.
AB  - Expression of Galalpha(1-3)Gal on endothelium has been implicated in the
      rejection of porcine xenografts. The aim of this study was to determine whether
      expression of Galalpha(1-3)Gal on pig islets varies between pigs aged 5, 12 and
      24 weeks, and to investigate whether it is expressed on islets isolated by
      collagenase digestion or islets maintained in tissue culture. Samples of pancreas
      were obtained from pigs aged 5, 12 and 24 weeks. Islets were isolated by manual
      collagenase digestion and density gradient separation. Samples were taken
      immediately after isolation or after maintenance in tissue culture. Pancreas and
      islet samples were processed, sectioned and stained with the lectin BS1-B4 (which
      binds to Galalpha(1-3)Gal residues), and anti-insulin antibody using a double
      staining technique. There was no significant difference in the staining patterns
      to sections of pancreas obtained from 5, 12 and 24 week old pigs. Vascular
      endothelium, connective tissue and the luminal surface of duct epithelial cells
      stained with BS1-B4 in all sections; endocrine and exocrine cells did not stain.
      Preliminary experiments showed that lectin staining to isolated islets was
      inconsistent between preparations, but expression did not appear to differ
      significantly between ages: lectin staining of some beta-cells was evident in the
      majority of freshly isolated preparations, but was not detectable on beta-cells
      following tissue culture. In conclusion, expression of Galalpha(1-3)Gal did not
      differ significantly in pancreata from 5, 12 and 24 week old pigs. Preliminary
      experiments showed that Galalpha(1-3)Gal was expressed by beta-cells immediately
      following isolation, but not after maintenance in culture.

PMID- 9930959
TI  - Neurosurgical interventions in the treatment of idiopathic Parkinson disease:
      neurostimulation and neural implantation.
AB  - With the exception of thalamotomy for drug-refractory tremor, surgical therapy
      for Parkinson's disease has been almost abandoned as treatment for Parkinsonian
      symptoms between 1965 and 1985. Reasons for this development relate to
      inconsistent postoperative results, complications associated with stereotactic
      surgical techniques and, most importantly, the advent of levodopa, which is still
      considered to be the gold standard in pharmacotherapy for Parkinson's disease.
      However, both, the long-term experience with L-DOPA therapy on the one hand and
      the progress of advanced stereotactic techniques and fetal graft research on the
      other hand have lead to reconsideration of surgical therapy in Parkinson's
      disease for patients, who can not be treated satisfactorily with medication. Both
      lesions (via thermocoagulation) and/or neurostimulation (via chronic
      intracerebral implantation of electrodes) in thalamic nuclei (nucleus ventralis
      oralis posterior/intermedialis thalami; VOP/VIM) may alleviate rest tremor in PD
      patients. In principle neurostimulation has the significant advantage of
      reversibility with regard to side effects in comparison to lesion surgery.
      Furthermore ventro-posterior pallidotomy or chronic stimulation in this
      structures may ameliorate bradykinesia and levodopa-induced dyskinesias.
      Additionally, "switching-off" the subthalamic nucleus by neurostimulation has
      been reported to reduce rigidity, bradykinesia and levodopa-induced ON-OFF
      fluctuations. On the other hand, neuronal transplantation of fetal nigral
      dopamine precursor cells aims at restoring the striatal dopamine deficit. Both
      animal and clinical experiments have shown that fetal grafts survive
      intrastriatal transplantation and may ensue moderate to satisfactory
      improvements, especially in regard to bradykinesia and ON-OFF-fluctuations.
      Further progress in the field of neuronal transplantation will largely depend on
      the development of alternative cell resources.

PMID- 9930958
TI  - Isokinetic gradient centrifugation prolongs survival of pig islets xenografted
      into mice.
AB  - Highly purified porcine islets were prepared by isokinetic gradients performed
      subsequently to isopycnic gradients. This additional purification step separates
      ductal, vascular, and lymphoid tissue effectively from endocrine tissue. Although
      ductal, vascular, and lymphoid tissue comprises only a minor contamination of the
      islet suspensions, a significant prolongation of the survival of porcine islets
      xenografted into streptozotocin diabetic C57BL/6 mice can be achieved by the
      elimination of the non-endocrine tissue. Rejection after islet transplantation is
      delayed from 2.2+/-0.4 days (n=27) to 13.1+/-2.1 days (n=36), respectively, when
      conventionally purified and highly purified islets are compared. Irrespective of
      the purification state, pretreatment of islets by low temperature culture had no
      effect on xenograft survival.

PMID- 9930960
TI  - Graves' disease: xenotransplantation model (athymic nude mice).
AB  - The immunological mechanisms leading to Graves' disease are not yet fully
      understood. The athymic nude mouse has immunological properties which allow in
      vivo studies concerning autoimmune thyroid diseases with special regard to the
      interaction of TSH, TSH receptor antibodies, cytokines, antithyroid drugs, TSH
      receptor antagonists and human lymphocytes. In our own studies thyroid tissues of
      patients with Graves' disease, toxic adenomas and non-toxic nodular goiter were
      xenotransplanted to athymic nude mice. Histology, morphology and function of the
      transplants were examined 2 days to 2 weeks after injection of bovine TSH,
      interferon-gamma, Graves' sera with or without addition of a TSH-receptor
      antagonist and lymphocytes of patients with Graves' disease. Thyroid transplants
      can be stimulated by TSH, interferon-gamma, Graves' sera and immunoglobulin G.
      Additional treatment with asialoagalacto-hCG inhibits stimulation of the
      immunoglobulin. Furthermore, preliminary results show, that engrafted peripheral
      and especially intrathyroidal lymphocytes from patients with Graves' disease
      specifically migrate into human thyroid transplants ("homing") and are able to
      induce functional and histological changes in these tissues. In summary, the
      xenotransplantation model is well suited for studies concerning pathogenesis,
      diagnosis and therapy of autoimmune thyroid diseases.

PMID- 9930961
TI  - Effects of retinol on follicular porcine thyrocytes in culture.
AB  - Retinoids influence proliferation and differentiation in transformed thyroid cell
      lines. Retinoids are able to damage cells by destabilizing lysosomal membranes
      and induce apoptosis in certain cell lines. In normal thyrocytes retinol
      modulates iodine metabolism. At concentrations higher than 50x10(-6) M retinoids
      are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this
      cytotoxicity is unknown. We studied the effect of 7-80x10(-6) M retinol on
      porcine follicular thyrocytes in culture. In order to differentiate between
      membrane-destabilizing effects and apoptosis we investigated cultures after
      incubation with retinol by light- and electron-microscopy and by labeling of
      potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP
      mediated DNA nick end labeling. We conclude that the observed cytotoxicity is
      caused mainly by the induction of apoptosis.

PMID- 9930962
TI  - Synergistic effect of microencapsulation and immunoalteration on islet allograft
      survival in bioartificial pancreas.
AB  - Recently, we reported successful transplantation (Tx) of microencapsulated (mc)
      islets. However, graft failure observed in several cases was associated with an
      increased foreign body reaction compared to long-term functioning grafts. This
      study was performed to investigate the impact of an immunoalterating islet
      pretreatment (12-14 days culture at 22 degrees C) on graft function. After
      microencapsulation in barium alginate beads the islets were cultured for another
      day. Diabetic LEWIS rats (blood glucose >19 mM) were transplanted with 3500
      immunoaltered mc-Wistar islets intraperitoneally. Controls were transplanted with
      3500 non-cultured syngeneic or allogeneic mc-islets. Additional syngeneic and
      allogeneic controls were transplanted with 6000 non-cultured, non-encapsulated
      islets intraperitoneally. Seventy percent of the recipients of microencapsulated,
      long-term low temperature cultured islets maintained normoglycemia at least for
      15 weeks, while this was true in only 17% of those animals receiving
      microencapsulated non-pretreated allogeneic islets. Islets in non-encapsulated
      controls were rejected within several days. Graft function correlated with
      histologically proven viable islets within the capsules. Microencapsulation of
      islets markedly prolonged allograft survival compared to non-encapsulated islets;
      application of an immunoaltering low-temperature culture further improved graft
      function significantly. These data may support the hypothesis of induction of a
      reaction against microcapsules by the antigen release from the graft which may be
      avoided by immunoaltering islet pretreatment.

PMID- 9930963
TI  - Factors influencing the properties and performance of microcapsules for
      immunoprotection of pancreatic islets.
AB  - There are several approaches of immunoprotection of pancreatic islets for the
      purpose of successful allo- or xenotransplantation in the absence of
      immunosuppressive medication. Extravascular approaches are either
      macroencapsulation (large numbers of islets together in one device) or
      microencapsulation. The latter approach is to envelop each individual islet in a
      semipermeable immunoprotective capsule. Quite promising results have been
      achieved with polylysine-alginate microencapsulated islet grafts in rodents, but
      clinical application is still restricted to a very small number of cases.
      Relevant considerations regard the following aspects. The biocompatibility of the
      microcapsules is influenced by the chemical composition of the materials applied
      and by mechanical factors related to the production process. With purified
      instead of crude alginates, the percentage of capsules with fibrotic overgrowth
      is reduced to approximately ten percent, and the remaining overgrowth is mainly
      explained by mechanical factors, i.e. inadequate encapsulation of individual
      islets. Even with purified alginates, however, the duration of encapsulated graft
      function is limited to a period of six to twenty weeks. Obviously, other factors
      than bioincompatibility play a role, which factors have to be identified. The
      limited duration of graft survival cannot be explained by rejection since, in
      rats, survival times of encapsulated isografts are similar, if not identical, to
      those of encapsulated allografts. An important factor is probably insufficient
      nutrition as a consequence of insufficient blood supply of the encapsulated and
      thus isolated islet. This also influences the functional performance of
      encapsulated islet grafts. Although normoglycemia can be readily obtained in
      streptozotocin diabetic rat recipients, glucose tolerance remains severely
      impaired, as a consequence of an insufficient increase of insulin levels in
      response to intravenous or oral glucose challenge. Important factors are the
      characteristics of the capsules applied in view of optimal diffusion kinetics,
      and the fact that an encapsulated islet graft can only be implanted in the
      peritoneal cavity because of its volume. Further studies should focus on finding
      a practically applicable method to reduce the barrier between encapsulated islets
      and the bloodstream, in order to improve both the functional performance and the
      survival of encapsulated islet grafts.

PMID- 9930964
TI  - Transplantation of islets using microencapsulation: studies in diabetic rodents
      and dogs.
AB  - Studies involving the transplantation of human islets in Type I diabetics have
      been of significant value both in documenting the potential importance of islet
      transplantation as a therapeutic modality, and in defining some of the problems
      which must be overcome before this approach can be used in large numbers of
      patients. The currently limited supply of adult human pancreatic glands, and the
      fact that chronic immunosuppression is required to successfully transplant islets
      into patients, indicate that techniques must be further developed and refined for
      allo- and xenografting of isolated islets from human and animal sources to
      diabetic patients. An increasing body of evidence using microencapsulation
      techniques strongly suggests that this will be achieved during the next few
      years. Data from our laboratory in rodents and dogs indicate that these systems
      can function for extended periods of time. In one study, insulin independence was
      achieved in spontaneously diabetic dogs by islet microencapsulation inside
      uncoated alginate gel spheres (Mr exclusion >600 kD). No synthetic materials or
      membrane coatings were employed in this study. Spheres containing canine islets
      were implanted into the peritoneum of 4 diabetic dogs. The animals received low
      dose CsA (levels below readable limits by HPLC at 3 weeks). Implantation of these
      spheres completely supplanted exogenous insulin therapy in the dogs for 60 to
      >175 days. Blood glucose concentration averaged 122+/-4 mg/dl for these animals
      during the first 2 months. The glycosylated hemoglobin (HbAIC) levels during this
      period dropped from 6.7+/-0.5% to 4.2+/-0.2% (P<0.001). IVGTT K-values at 1 and 2
      months postimplantation were 1.6+/-0.1 (P<0.002) and 1.9+/-0.1 (P<0.001),
      respectively compared with 0.71+/-0.3 before implantation. In a second group of
      studies, bovine islets were immobilized inside a new type of selectively
      permeable "microreactor" (Mr exclusion <150 kD) and implanted into the peritoneum
      of 33 STZ-induced diabetic rats without any immunosuppression. Diabetes was
      promptly reversed, and normoglycemia maintained for periods of several weeks to
      months. Immunohistochemical staining of microreactors recovered from these
      animals revealed well-granulated beta-cells consistent with functionally active
      insulin synthesis and secretion. To test further the secretory function of the
      islets, some of the explanted microreactors were incubated in media containing
      either basal or stimulatory concentrations of glucose. The islets responded with
      an approximately 3- to 5-fold average increase above basal insulin secretion.
      These results are encouraging, and may have important implications in assessing
      the potential role of these microencapsulation systems as therapy for human
      insulin-dependent diabetes.

PMID- 9930965
TI  - In vivo delivery of recombinant human growth hormone from genetically engineered
      human fibroblasts implanted within Baxter immunoisolation devices.
AB  - Continuous delivery of therapeutic peptide to the systemic circulation would be
      the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a
      membrane encapsulation system developed for implantation of tissues, cells such
      as endocrine cells or cell lines genetically engineered for therapeutic peptide
      delivery in vivo. To demonstrate the utility of this system, cell lines were
      developed which expressed human growth hormone (hGH) at levels exceeding 1
      microgram per million cells per day. These were loaded into devices which were
      then implanted into juvenile nude rats. Significant levels of hGH of up to 2.5
      ng/ml were detected in plasma throughout the six month duration of the study. In
      contrast, animals implanted with free cells showed peak plasma levels of 0.5 to
      1.2 ng four days after implantation with no detectable hGH beyond 10 days.
      Histological examination of explanted devices showed they were vascularized and
      contained cells that were viable and morphologically healthy. After removal of
      the implants, no hGH could be detected which confirmed that the source of hGH was
      from cells contained within the device. The long term expression of human growth
      hormone as a model peptide has implications for the peptide therapies for a
      variety of human diseases using membrane encapsulated cells.

PMID- 9930966
TI  - Analysis of the cellular reaction towards microencapsulated xenogeneic islets
      after intraperitoneal transplantation.
AB  - Xenotransplantation of encapsulated islets of Langerhans is a possibility to
      overcome problems of human organ donor shortage in islet transplantation.
      Preexisting natural xenoantibodies are known to play a major role in the
      rejection of vascularized xenografts. Only little is known about the mechanism of
      rejection of non-vascularized cellular xenotransplants. In this study we
      introduce a method for the characterization of xenograft rejection of
      encapsulated islets by FACS analysis of peritoneal cells. Pig islets were
      transplanted intraperitoneally into non-diabetic Lewis rats either encapsulated
      or non-encapsulated. Animals receiving empty capsules and sham-operated animals
      served as controls. After 7 days a peritoneal lavage was performed. The total
      cell number and the viability of the cells were determined. Cells were analysed
      after staining with a panel of antibodies for the detection of T-lymphocytes, B
      lymphocytes, macrophages, MHC class II molecules. Total cell number was highest
      after microencapsulated transplantation (149.4+/-30.1x10(6)) compared with empty
      capsules (41.4+/-19.7x10(6)) and non-encapsulated porcine islets (18.1+/
      3.3x10(6)). The percentage of CD 3 positive T-lymphocytes rose to 44.5+/-11.5% in
      case of microencapsulated xenografts compared with 19.2+/-8.2% for non
      encapsulated xenografts and 4.9+/-2.4% for empty controls. B-lymphocytes were
      detected in only small amounts. MHC class II expression on macrophages as
      activation marker was significantly increased after encapsulated transplantation
      (60.2+/-8.9% vs 15.2+/-7.0% for free islets and 4.9+/-1.2% for empty controls).
      The discrepancy between the macrophage activation due to encapsulated xenogeneic
      islets in comparison to empty capsules made from the same material clearly
      indicates that the reaction is not only material related but that a recognition
      of the encapsulated islet takes place despite the effective inhibition of a
      direct cell-to-cell contact. This recognition occurs on a T-cell level as well as
      on the macrophage level. 7 days after transplantation the reaction towards
      encapsulated xenografts is even more intense than to non-encapsulated xenografts.
      This might be due either to the time course of the rejection process or to a
      prolongation of the activation because antigen elimination is hindered by the
      capsule.

PMID- 9930967
TI  - Correction of diabetic nod mice with insulinomas implanted within Baxter
      immunoisolation devices.
AB  - Insulin replacement by injection is clearly not a cure for Insulin Dependent
      Diabetes Mellitus (IDDM). Replacement of the destroyed islets by pancreas or
      islet allograft transplantation can achieve the good metabolic control required
      to prevent diabetic complications, but tissue supply is limited. The problem of
      islet supply to treat the 1 million IDDM patients in the USA could be overcome by
      using immortalized islet beta-cells as a donor source. However, before either
      allogeneic or xenogeneic immortalized beta-cells are used, some major problems
      have to be overcome: control of immortalized cell growth, allograft or xenograft
      rejection and recurrence of autoimmunity. To tackle these problems we have used a
      cell impermeable immunoisolation device containing mouse insulinoma cells.
      Transplantation of devices with insulinomas from NOD mice carrying the Rat
      insulin promoter regulated SV40 T-Antigen transgene (RIP-TAg), normalized the
      blood glucose levels of diabetic NOD mice. Insulinomas from allogeneic CBA/NOD
      RIP-TAg mice were also capable of normalizing diabetic NOD mice. Not only were
      non-fasting blood glucoses normalized but when given an intraperitoneal injection
      of glucose, the corrected mice had a near normal clearance of glucose from the
      blood. When the devices were removed from normalized mice they became diabetic
      again, demonstrating that the immunoisolation device was capable of protecting
      against both alloimmune and autoimmune destruction. The results with allogeneic
      mouse beta-cells suggest the possibility that immortalized human beta-cells could
      be an effective source of tissue to correct diabetes in IDDM patients without the
      use of immunosuppression.

PMID- 9930968
TI  - New approaches for control of anti-self reactivity in type 1 diabetes mellitus
      and transplantation of pancreatic islets.

PMID- 9930969
TI  - Prevention of autoimmune but not allogeneic destruction of grafted islets by
      different therapeutic strategies.
AB  - Grafting autoimmune-diabetic recipients with allogeneic islets, graft rejection
      and disease recurrence as major problems of reaching indefinite survival and
      tolerance induction have to be solved. Anti-CD25 and anti-CD4 monoclonal
      antibodies were successfully used after allogeneic islet transplantation in
      experimentally diabetic rats. A temporary anti-CD25 therapy also prevented
      disease recurrence in autoimmune-diabetic BB rats, while this was not yet
      reported for an anti-CD4 treatment. In autoimmune-diabetic NOD mice disease
      recurrence can be successfully treated using an anti-CD4 monoclonal antibody. We,
      therefore, compared the efficacy of a short-term anti-CD25 and anti-CD4 treatment
      regarding the prevention of allograft rejection and disease recurrence in
      autoimmune-diabetic BB/OK rats. Both monoclonal antibodies were combined with low
      doses of Cyclosporin A. Untreated BB/OK rats relapsed into hyperglycaemia within
      3 weeks independent of the islet donor, LEW.1A, LEW.1BB/OK or BB/OK rats.
      However, after grafting MHC-identical allogeneic (LEW.1BB/OK) or syngeneic
      (BB/OK) islets we observed about 30% spontaneous acceptance. Both the anti-CD25
      and anti-CD4 therapy significantly prolonged the survival of allogeneic grafted
      islets. After MHC-identical allogeneic and syngeneic islet transplantation the
      temporary immunotherapy increased the proportion of permanent acceptors to 63%
      and 75%, respectively. The efficacy of both treatment strategies in prolonging
      allograft survival and prevention of disease recurrence was identical. In
      summary, anti-CD25 as well as anti-CD4 therapy prevented autoimmune but not
      allogeneic islet destruction in autoimmune-diabetic BB/OK rats. In conclusion,
      targeting different immune cells by monoclonal antibodies with different
      specificities can lead to very similar results with respect to an interruption of
      allograft rejection and autoimmune reaction.

PMID- 9930970
TI  - Generation of nonimmune islet cells using genetic engineering.

PMID- 9930971
TI  - Engineering cultured insulin-secreting pancreatic B-cell lines.
AB  - Despite many triumphs, a significant limitation of the usefulness of many of the
      available B-cell lines for the study of insulin secretion are either
      inappropriate or lack of responsiveness to glucose. Commonly employed cell lines
      generated prior to the 1990s following X-ray irradiation (RINm5F cells) or simian
      virus 40 B-cell transformation (HIT-T15 cells and BTC) fall into this category.
      More recent success has been achieved with the generation of INS-1 cells and MIN6
      cells, but the production of these cell lines owes much to good fortune,
      dedication and hard work. In the present era, molecular biology techniques
      provide the opportunity to engineer novel pancreatic B-cell lines which possess
      many attributes of normal insulin-secreting cells. This review describes the
      electrofusion of normal NEDH rat pancreatic B-cells with immortal RINm5F cells to
      create three new glucose-responsive clonal insulin-secreting cells, designated
      BRIN-BG5, BRIN-BG7 and BRIN-BD11. These cell lines exhibit up to four-fold
      insulin-secretory responses to depolarization with 25 mmol/l K+, 7.68 mmol/l
      Ca2+, 10 mmol/l L-alanine, and activation of protein kinase C or adenylate
      cyclase with 10 nmol/l phorbol- 12-myristate-13-acetate or 25 micromol/l
      forskolin, respectively. The maximal insulin-secretory response of both BRIN-BG5
      and BRIN-BG7 cells to glucose occurred at 8.4 mmol/l (1.9- and 1.8-fold
      increases, respectively). In contrast, 4.2-16.7 mmol/l glucose evoked a stepwise
      2- to 3-fold of insulin release from BRIN-BD11 cells. The superior glucose
      responsiveness of BRIN-BD11 cells compared with BRIN-BG5 or BRIN-BG7 cells was
      associated with increased expression of GLUT-2 and a greater contribution of
      glucokinase to total glucose phosphorylating enzyme activity. Furthermore, BRIN
      BD11 cells also showed appropriate responses to a diverse range of modulators of
      pancreatic B-cell function, including amino acids, neurotransmitters and
      sulphonylurea drugs. Collectively these observations indicate that genetic
      modification of insulin-secreting cells by electrofusion (or transfection with
      cDNA) offers a new avenue for generation of useful clonal glucose-responsive
      pancreatic B-cell lines for studies of insulin secretion and transplantation in
      insulin-dependent diabetes mellitus.

PMID- 9930973
TI  - Human proinsulin production in primary rat hepatocytes after retroviral vector
      gene transfer.
AB  - The development of autologous somatic cells, engineered for the synthesis and
      release of human insulin under physiological stimuli, would certainly represent a
      major breakthrough in the therapy of insulin-dependent diabetes mellitus. We
      generated a retroviral vector containing the human proinsulin cDNA and the gene
      coding for the human nerve growth factor receptor for quantitative analysis of
      transduced cells. Primary rat hepatocytes were selected as target cells because
      of the constitutive expression of the pancreatic beta-cell glucose transporter
      GLUT-2 and the glycolitic enzyme glucokinase. Appropriate conditions for culture
      and retroviral transduction are described. The highest transduction efficiency,
      evaluated as percentage of LNGFr expressing cells was obtained by repeated
      infection cycles (40+/-10%). Human proinsulin accumulated in the culture medium
      of transduced rat hepatocytes (mean+/-SD): 18.1+/-7.9 (range 8.7-36.4)
      ng/24h/10(6) cells. Primary rat hepatocytes can be efficiently transduced by a
      retroviral vector and the de novo synthesis of human proinsulin can be induced.
      Primary cultured hepatocytes represent an useful model to test retroviral
      constructs engineered for the glucose-inducible expression of insulin under the
      control of liver-specific promoters.

PMID- 9930972
TI  - Prospects for insulin delivery by ex-vivo somatic cell gene therapy.
AB  - The principle of insulin delivery by ex-vivo somatic cell gene therapy involves
      the removal of non-B-cell somatic cells (e.g. fibroblasts) from a diabetic
      patient, and genetically altering them in vitro to produce and secrete insulin.
      The cells can be grown in culture and returned to the donor as a source of
      insulin replacement. Cells modified in this way could be evaluated before
      implantation, and reserve stocks could be cryopreserved. By using the patient's
      own cells, the procedure should obviate the need for immunosuppression and
      overcome the problem of tissue supply, while avoiding a recurrence of cell
      destruction. Ex-vivo somatic cell gene therapy requires an accessible and robust
      cell type that is amenable to multiple transfections and subject to controlled
      proliferation. Special problems associated with the use of non-B-cell somatic
      cells include the processing of proinsulin to insulin, and the conferment of
      sensitivity to glucose-stimulated proinsulin biosynthesis and regulated insulin
      release. Preliminary studies using fibroblasts, pituitary cells, kidney (COS)
      cells and ovarian (CHO) cells suggest that these challenges could be met, and
      that ex-vivo somatic cell gene therapy offers a feasible approach to insulin
      replacement therapy.

PMID- 9930974
TI  - Substrate recognition by "password" in p-hydroxybenzoate hydroxylase.
AB  - The flavin of p-hydroxybenzoate hydroxylase (PHBH) adopts two conformations
      [Gatti, D. L., Palfey, B. A., Lah, M.-S., Entsch, B., Massey, V., Ballou, D. P.,
      and Ludwig, M. L. (1994) Science 266, 110-114; Schreuder, H. A., Mattevi, A.,
      Obmolova, G., Kalk, K. H., Hol, W. G. J., van der Bolt, F. J. T., and van Berkel,
      W. J. H. (1994) Biochemistry 33, 10161-10170]. Kinetic studies detected the
      movement of the flavin from the buried conformation to the exposed conformation
      caused by the binding of NADPH prior to its reaction with the flavin. The pH
      dependence of the rate constant for flavin reduction in wild-type PHBH and the
      His72Asn mutant indicates that the deprotonation of bound p-hydroxybenzoate is
      also required for flavin movement, and is accomplished by the same internal
      proton transport network previously found to be involved in substrate oxidation.
      The linkage of substrate deprotonation to flavin movement constitutes a novel
      mode of molecular recognition in which the enzyme tests the suitability of
      aromatic substrates before committing to the catalytic cycle.

PMID- 9930975
TI  - Stereochemical constraints on the substrate specificity of phosphotriesterase.
AB  - A series of achiral, chiral, and racemic mixtures of paraoxon analogues
      containing various combinations of methyl, ethyl, isopropyl, or phenyl
      substituents were synthesized as probes of the stereochemical constraints within
      the active site of phosphotriesterase. The kinetic constants for these paraoxon
      analogues with the enzyme varied significantly with the size of substituents
      surrounding the phosphorus center. These results indicate that binding and
      catalysis depend significantly on the relative size and orientation of the two
      subsites that must accommodate the coordination of the alkyl or aryl substituents
      within the enzyme active site. Individual enantiomers of paraoxon analogues were
      also synthesized and the stereochemical specificity for phosphotriesterase
      determined. In general, the kinetic constants, kcat and kcat/Km, for the (-)
      enantiomers of these phosphotriesters were 1-2 orders of magnitude greater than
      the (+)-enantiomers. In every case, the preferred isomer is of the SP
      configuration. For example, the kcat/Km for SP-(-)-ethyl phenyl p-nitrophenyl
      phosphate is 1.8 x 10(8) M-1 s-1 but is only 1.8 x 10(6) M-1 s-1 for the RP-(+)
      isomer. These results suggest that one enantiomer is positioned for hydrolysis
      more favorably than the other enantiomer. The inactivation of
      acetylcholinesterase with the same series of organophosphate nerve agents was
      also measured. The stereoisomer that more rapidly inactivates human
      acetylcholinesterase is hydrolyzed more slowly than its enantiomer by the
      phosphotriesterase.

PMID- 9930976
TI  - Effect of cytarabine on the NMR structure of a model okazaki fragment from the
      SV40 genome.
AB  - Okazaki fragments occur as intermediates during lagging strand DNA replication.
      Alterations in Okazaki fragment structure may contribute to the anticancer
      activities of nucleoside analogues such as cytarabine, a potent anti-leukemic
      agent that inhibits lagging strand replication. We have determined the solution
      structures for two model Okazaki fragments, [OKA] and [ARAC]. These sequences are
      derived from a frequent initiation site for primase during replication of the SV
      40 viral genome. The sequence of [ARAC] differs from [OKA] only by substitution
      of cytarabine for one deoxycytidine. The structure of each model Okazaki fragment
      was elucidated using NMR spectroscopy and restrained molecular dynamics
      simulations. The solution structures of [OKA] and [ARAC] each consist of two
      distinct domains: a DNA duplex region (DDR) and an RNA-DNA hybrid duplex region
      (HDR). The DDR of [OKA] adopts geometry similar to B-form except for variations
      in helical parameters, especially twist and roll, which occur in the purine
      tract, increasing base overlap among the five consecutive purines. The helical
      axes for the DDR and HDR of [OKA] are bent 22 degrees relative to one another.
      Although the local structures for the DDR and HDR of [ARAC] are similar to those
      in [OKA] (root-mean-square deviation (rmsd) approximately 0.8, 1.7 A), the
      bending at the junction is different (41 degrees for [ARAC] vs 22 degrees for
      [OKA]). Increased helical bending of cytarabine-substituted Okazaki fragments may
      contribute to the propensity of cytarabine to inhibit elongation of the lagging
      strand during DNA replication, and in effecting anticancer activity.

PMID- 9930977
TI  - The active site of Paracoccus denitrificans aromatic amino acid aminotransferase
      has contrary properties: flexibility and rigidity.
AB  - Paracoccus denitrificans aromatic amino acid aminotransferase (EC 2. 6.1.57;
      pdAroAT) binds with a series of aliphatic monocarboxylates attached to the bulky
      hydrophobic groups. To analyze the properties of the active site in this enzyme,
      we determined the tertiary structures of pdAroAT complexed with nine different
      inhibitors. Comparison of these active site structures showed that the active
      site of pdAroAT consists of two parts with contrary properties: rigidity and
      flexibility. The regions that interact with the carboxylates and methylene chains
      of the inhibitors gave essentially the same structures among these complexes,
      exhibiting the rigid property, which would involve fixing the substrate at the
      proper orientation for efficient catalysis. The region that interacts with the
      terminal hydrophobic groups of the inhibitors gave versatile structures according
      to the structures of the terminal groups, showing that this region is
      structurally flexible. This is mainly achieved by the conformational versatility
      of the side chains of Asp15, Lys16, Asn142, Arg292, and Ser296. These residues
      formed in the active site hydrogen bond networks, which were adaptable for the
      structures of the terminal hydrophobic groups of the inhibitors, with a small
      deformation or partial destruction according to the shapes and sizes of the
      inhibitors. These observations illustrate how the flexibility and rigidity in the
      active site can be used for the substrate binding and recognition.

PMID- 9930978
TI  - Factor VIIa's first epidermal growth factor-like domain's role in catalytic
      activity.
AB  - Factor VIIa-tissue factor complex formation initiates the extrinsic blood
      coagulation pathway. We investigated factor VIIa's first epidermal growth factor
      like (egf1) domain's role in the catalytic activity increase caused when factor
      VIIa binds tissue factor. Starting with a factor VIIa with factor IX's egf1
      domain (factor VII(IXegf1)a), we made 4 proteins with egf1 residues changed to
      those in factor VIIa, including E51A, D64Q, FG74-75PA, and K79R. We measured each
      enzyme's affinity for tissue factor and determined the enzymes' kinetic constants
      with and without tissue factor. The Kd for factor VII(IXegf1)a binding to tissue
      factor was 60-200-fold higher than that of factor VIIa depending on the assay
      employed. Only factor VII(IXegf1)a with the K79R (K79Ra) mutation, among all the
      mutants, had an effect on binding with a Kd 3-8-fold lower than that of factor
      VII(IXegf1)a. In kinetic analyses with a small peptide substrate, in the absence
      of tissue factor, factor VIIa, factor VII(IXegf1)a, and K79Ra had similar kcat's
      and Km's. With tissue factor, due to a kcat decrease, factor VII(IXegf1)a's
      catalytic efficiency (kcat/Km) was 2-fold lower than factor VIIa's. K79Ra's
      catalytic efficiency was intermediate between those of factor VIIa and factor
      VII(IXegf1)a. With factor X as substrate, in the absence of tissue factor, K79Ra
      and factor VII(IXegf1)a had catalytic efficiencies 1.5-fold and 2-fold lower than
      that of factor VIIa. In contrast, with tissue factor and with factor X as
      substrate, due to higher Km's, factor VII(IXegf1)a and K79Ra had only 9% and 33%
      of factor VIIa's catalytic efficiency. Our results suggest the egf1 domain's role
      in tissue factor binding involves critical alignment of tissue factor with factor
      VIIa's catalytic domain. Proper alignment in turn promotes optimal catalytic
      activities.

PMID- 9930979
TI  - Functions of His107 in the catalytic mechanism of human glutathione S-transferase
      hGSTM1a-1a.
AB  - Domain interchange analyses and site-directed mutagenesis indicate that the
      His107 residue of the human subunit hGSTM1 has a pronounced influence on
      catalysis of nucleophilic aromatic substitution reactions, and a H107S
      substitution accounts for the marked differences in the properties of the
      homologous hGSTM1-1 (His107) and hGSTM4-4 (Ser107) glutathione S-transferases.
      Reciprocal replacement of His107 and Ser107 in chimeric enzymes results in
      reciprocal conversion of catalytic properties. With 1-chloro-2, 4-dinitrobenzene
      as a substrate, the His107 residue primarily influences the pH dependence of
      catalysis by lowering the apparent pKa of kcat/Km from 7.8 for the Ser107
      containing enzymes to 6.3 for the His107-containing enzymes. There is a parallel
      shift in the pKa for thiolate anion formation of enzyme-bound GSH. Y6F mutations
      have no effect on the pKa for these enzymes. Crystal structures of hGSTM1a-1a
      indicate that the imidazole ring of His107 is oriented toward the substrate
      binding cleft approximately 6 A from the GSH thiol group. Thus, His107 has the
      potential to act as a general base in proton transfer mediated through an active
      site water molecule or directly following a modest conformational change, to
      promote thiolate anion formation. All wild-type enzymes and H107S chimera have
      nearly identical equilibrium constants for formation of enzyme-GSH complexes (Kd
      values of 1-2 x 10(-)6 M); however, KmGSH and Ki values for S-methylglutathione
      inhibition determined by steady-state kinetics are nearly 100-fold higher. The
      functions of His107 of hGSTM1a-1a are unexpected in view of a substantial body of
      previous evidence that excluded participation of histidine residues in the
      catalytic mechanisms of other glutathione S-transferases. Consequences of His107
      involvement in catalysis are also substrate-dependent; in contrast to 1-chloro
      2,4-dinitrobenzene, for the nucleophilic addition reaction of GSH to ethacrynic
      acid, the H107S substitution has no effect on catalysis presumably because
      product release is rate-limiting.

PMID- 9930981
TI  - Detailed active site configuration of a new crystal form of methanol
      dehydrogenase from Methylophilus W3A1 at 1.9 A resolution.
AB  - The three-dimensional structure of a new crystal form of methanol dehydrogenase
      from Methylophilus W3A1 has been obtained in the presence of substrate using data
      recorded at a synchrotron. The structure of this approximately 140 kDa
      heterotetramer, refined at 1. 9 A resolution, reveals the detailed configuration
      of its redox cofactor, pyrroloquinoline quinone (PQQ). C4, one of the oxygen
      bearing atoms of this orthoquinone is in a planar configuration while C5, which
      bears the other quinone oxygen, is tetrahedral, suggesting that the PQQ is in the
      semiquinone redox state. The substrate binding site has been identified close to
      PQQ and to the side chain of Asp297, the putative active site base. The proximity
      of the hydroxyl of methanol to C5 of PQQ compared to the greater separation of
      the substrate methyl group from C5 supports the addition-elimination reaction
      mechanism involving a hemiketal intermediate.

PMID- 9930980
TI  - Fragment reconstitution of a small protein: folding energetics of the
      reconstituted immunoglobulin binding domain B1 of streptococcal protein G.
AB  - To elucidate early stages in protein folding, we have adopted a fragment
      reconstitution method for small proteins. This approach is expected to provide
      nuclei for protein folding and to allow us to investigate folding mechanisms. In
      previous work [Kobayashi, N., et al. (1995) FEBS Lett. 366, 99-103.] we
      demonstrated the association of two complementary fragments, derived from the
      immunoglobulin G-binding domain B1 of streptococcal Protein G, and showed the
      structural similarity between the reconstituted domain and the uncleaved wild
      type domain. In this work we have further characterized the reconstituted domain
      as well as the uncleaved domain thermodynamically by means of differential
      scanning calorimetry (DSC) and circular dichroism (CD) measurements. Although
      composed of short peptide fragments not linked by covalent bonds, the
      reconstituted domain showed a typical folding/unfolding curve in both DSC and CD
      melting measurements and behaved like a globular protein. The domain was not very
      stable, and the small value of the Gibbs free energy corresponded to the class of
      the weakest protein-protein binding systems. The denaturation temperature of 0.
      78 mM solution was 313 K at pH 5.9 as measured by DSC, which was more than 40
      degrees lower than the uncleaved domain. This apparent instability was primarily
      caused by entropic disadvantage attributed to a bimolecular reaction. The
      temperature dependence of the enthalpy change from the folded to the unfolded
      state was almost identical for the reconstituted domain and the uncleaved one.
      This indicates that most of the noncovalent intramolecular interactions
      stabilizing the native structure, such as hydrogen bonding and hydrophobic
      interactions, are regenerated in the reconstituted domain. By comparing the
      equilibrium constants of the reconstituted and uncleaved domains, we determined
      the effective concentration to be approximately 6 M at 298 K. Structure-based
      estimation of the thermodynamic properties from the values of accessible surface
      areas showed that approximately 35% of the total heat capacity change and
      approximately 25% of the total enthalpy change can be attributed to the
      interchain interaction at 298 K. Furthermore, the folding/unfolding equilibrium
      of beta-hairpin structure of the fragment 41-56 alone was also characterized.
      These analyses allow us to envision the microdomain folding mechanism of the
      Protein G B1 domain, in which segment 41-56 first forms a stable beta-hairpin
      structure and then collides with segment 1-40, followed by spontaneous folding of
      the whole molecule.

PMID- 9930982
TI  - Studies on the catalysis of carbon-cobalt bond homolysis by ribonucleoside
      triphosphate reductase: evidence for concerted carbon-cobalt bond homolysis and
      thiyl radical formation.
AB  - Ribonucleotide reductases (RNRs) catalyze the rate-determining step in DNA
      biosynthesis: conversion of nucleotides to deoxynucleotides. The RNR from
      Lactobacillus leichmannii utilizes adenosylcobalamin (AdoCbl) as a cofactor and,
      in addition to nucleotide reduction, catalyzes the exchange of tritium from [5'
      3H]-AdoCbl with solvent. Examination of this exchange reaction offers a unique
      opportunity to investigate the early stages in the nucleotide reduction process
      [Licht S. S., Gerfen, G. J., and Stubbe, J. (1996) Science 271, 477-481]. The
      kinetics of and requirements for this exchange reaction have been examined in
      detail. The turnover number for 3H washout is 0.3 s-1, and it requires an
      allosteric effector dGTP (Km = 17 +/- 3 microM), AdoCbl (Km = 60 +/- 9 microM)
      and no external reductant. The effects of active-site mutants of RTPR (C119S,
      C419S, C731S, C736S, and C408S) on the rate of the exchange reaction have been
      determined, and only C408 is essential for this process. The exchange reaction
      has previously been monitored by stopped-flow UV-vis spectroscopy, and
      cob(II)alamin was shown to be formed with a rate constant of 40 s-1 [Tamao, Y.,
      and Blakley, R. L. (1973) Biochemistry 12, 24-34]. This rate constant has now
      been measured in D2O, with [5'-2H2]-AdoCbl in H2O, and with [5'-2H2]-AdoCbl in
      D2O. A comparison of these results with those for AdoCbl in H2O revealed kH/kD of
      1.6, 1.7, and 2.7, respectively. The absolute amounts of cob(II)alamin generated
      with [5'-2H2]-AdoCbl in D2O in comparison with AdoCbl in H2O reveal twice as much
      cob(II)alamin in the former case. Similar transient kinetic studies with C408S
      RTPR reveal no cob(II)alamin formation. These experiments allow proposal of a
      minimal mechanism for this exchange reaction in which RNR catalyzes homolysis of
      the carbon-cobalt bond in a concerted fashion, to generate a thiyl radical on
      C408, cob(II)alamin, and 5'-deoxyadenosine.

PMID- 9930983
TI  - Thermodynamic and kinetic studies on carbon-cobalt bond homolysis by
      ribonucleoside triphosphate reductase: the importance of entropy in catalysis.
AB  - In the catalytic mechanism of nucleotide reduction, ribonucleoside triphosphate
      reductase (RTPR) from Lactobacillus leichmannii catalyzes the homolytic cleavage
      of the carbon-cobalt bond of adenosylcobalamin (AdoCbl) at a rate approximately
      10(11)-fold faster than the uncatalyzed reaction. Model systems have suggested
      hypotheses for the thermodynamic basis of this reaction, but relevant
      measurements of the enzymatic reaction have been lacking. To address this
      question in a system for which the microscopic rate constants can be measured as
      a function of temperature, we examined the RTPR-catalyzed exchange reaction.
      RTPR, in the presence of allosteric effector dGTP and in the absence of
      substrate, catalyzes carbon-cobalt bond homolysis and formation of a thiyl
      radical from an active-site cysteine in a concerted fashion [Licht, S., Booker,
      S. , Stubbe, J. (1999) Biochemistry 38, 1221-1233]. Both the kinetics of
      cob(II)alamin formation and the amounts of cob(II)alamin formed have been studied
      as a function of AdoCbl concentration and temperature. Analysis of these data has
      allowed calculation of a DeltaH of 20 kcal/mol, a DeltaS of 70 cal mol-1 K-1, a
      DeltaH of 46 kcal/mol, and a DeltaS of 96 cal mol-1 K-1 for carbon-cobalt bond
      homolysis/thiyl radical formation. The results further show that the enzyme
      perturbs the equilibrium between the reactant (AdoCbl-bound) state and the
      product (cob(II)alamin/5'-deoxyadenosine (5'-dA)/thiyl radical state, making them
      approximately equal in energy. The thermodynamic perturbation, in addition to
      transition-state stabilization, is required for the large rate acceleration
      observed. Entropic, rather than enthalpic, factors make the largest contribution
      in both cases.

PMID- 9930984
TI  - Quaternary structure sensitive tyrosine residues in human hemoglobin: UV
      resonance raman studies of mutants at alpha140, beta35, and beta145 tyrosine.
AB  - Recent studies noted the contribution of alpha42Tyr to the T-R-dependent UV
      resonance Raman (UVRR) spectral changes of HbA [Nagai, M., et al. (1996) J. Mol.
      Struct. 379, 65-75; Huang, S., et al. (1997) Biochemistry 36, 6197-6206], but the
      observed UVRR changes of the Tyr residue cannot be fully interpreted with
      alpha42Tyr alone. To identify the remaining contributions, the 235 nm-excited
      UVRR spectra of Tyr mutant Hbs at alpha140, beta35, and beta145 were investigated
      here. The Fe-His stretching mode demonstrated that all of these mutant Hbs take
      the T structure in the deoxy form under these experimental conditions. The UVRR
      change of the Trp residue of these mutants upon the T-R transition was the same
      as that in HbA, indicating that the T-R-dependent UVRR change of beta37Trp is not
      due to stacking with Tyr residues but is due to the formation or destruction of a
      hydrogen bond. The recombinant Hbs beta35Tyr --> Phe and beta35Tyr --> Thr both
      exhibited UVRR spectra identical with that of HbA, meaning that beta35Tyr is not
      responsible. In the spectra of des(beta146His,beta145Tyr)Hb with inositol
      hexaphosphate, the frequency shift of the Tyr RR bands was the same as that in
      HbA but the intensity enhancement in the CO form was small, suggesting that
      beta145Tyr contributes to a part of the intensity change, but scarcely relates to
      the frequency shift. In the spectra of Hb Rouen (alpha140Tyr --> His), the
      frequency shifts of bands at 1617 (Y8a) and 1177 (Y9a) cm-1 following ligation
      were half of those in HbA, while the intensity enhancement was not detected. This
      result means that alpha140Tyr is responsible for both the frequency shift and the
      intensity changes. It is suggested that the frequency shift of the Tyr RR bands
      upon the T --> R transition is due to changes in the hydrogen bonding state of
      alpha42- and alpha140Tyr and that the intensity enhancement is due to changes in
      the environment of the penultimate Tyr in both alpha and beta subunits (alpha140
      and beta145). These alterations in the vibrational spectra clearly demonstrate
      which tyrosine residues are involved in the T-R transition as a result of
      modification of their local environments.

PMID- 9930985
TI  - EPR kinetic studies of oxygen release in thylakoids and PSII membranes: a kinetic
      intermediate in the S3 to S0 transition.
AB  - Time-resolved EPR oximetry has been used to determine the oxygen release kinetics
      in spinach thylakoids and PSII membranes. We observe release kinetics with half
      times of approximately 0.85 and approximately 1.45 ms for thylakoids and PSII
      membranes, respectively, which are in close agreement with the EPR determined Yz
      decay kinetics for the S3 --> --> S0 transition in these systems. The results
      show conclusively that water-oxygen chemistry is not a rate-limiting step in the
      donor side of PSII under normal turnover conditions. By analyzing the oxygen
      release kinetics in thylakoids under nonphysiological, but still functionally
      competent conditions (low pH or high salt), we observed an initial delay in the
      O2 release of up to 200 microseconds following flash turnover from the S3 state.
      This is the first direct indication of a probable quasi-stable intermediate in
      the S3 --> --> S0 turnover of PSII, possibly representing the putative S4 state.
      Under conditions more closely approaching physiological, no such delay was
      resolved, indicating that the S4 --> O2 transition occurs within 50 microseconds
      under such circumstances. Two possible reaction sequences for O2 formation
      consistent with these and other data are discussed. It is suggested that the more
      probable form of "S4" is in fact the S3 + Yz* combination, which must undergo
      some molecular rearrangement on the tens to hundreds of microseconds time scale
      before O2 formation chemistry occurs.

PMID- 9930986
TI  - Tyrosine-Z in oxygen-evolving photosystem II: a hydrogen-bonded tyrosinate.
AB  - In oxygen-evolving photosystem II (PSII), a tyrosine residue, D1Tyr161 (YZ),
      serves as the intermediate electron carrier between the catalytic Mn cluster and
      the photochemically active chlorophyll moiety P680. A more direct catalytic role
      of YZ, as a hydrogen abstractor from bound water, has been postulated. That YZox
      appears as a neutral (i.e. deprotonated) radical, YZ*, in EPR studies is
      compatible with this notion. Data based on electrochromic absorption transients,
      however, are conflicting because they indicate that the phenolic proton remains
      on or near to YZox. In Mn-depleted PSII the electron transfer between YZ and
      P680+ can be almost as fast as in oxygen-evolving material, however, only at
      alkaline pH. With an apparent pK of about 7 the fast reaction is suppressed and
      converted into an about 100-fold slower one which dominates at acid pH. In the
      present work we investigated the optical difference spectra attributable to the
      transition YZ --> YZox as function of the pH. We scanned the UV and VIS range and
      used Mn-depleted PSII core particles and also oxygen-evolving ones. Comparing
      these spectra with published in vitro and in vivo spectra of phenolic compounds,
      we arrived at the following conclusions: In oxygen-evolving PSII YZ resembles a
      hydrogen-bonded tyrosinate, YZ(-).H(+).B. The phenolic proton is shifted toward a
      base B already in the reduced state and even more so in the oxidized state. The
      retention of the phenolic proton in a hydrogen-bonded network gives rise to a
      positive net charge in the immediate vicinity of the neutral radical YZ*. It may
      be favorable both for the very rapid reduction by YZ of P680+ and for electron
      (not hydrogen) abstraction by YZ* from the Mn-water cluster.

PMID- 9930987
TI  - Membrane-bound electron transfer chain of the thermohalophilic bacterium
      Rhodothermus marinus: a novel multihemic cytochrome bc, a new complex III.
AB  - A novel multihemic cytochrome bc complex was isolated from the membranes of
      Rhodothermus marinus. It is a complex with a minimum of three subunits (43, 27,
      and 18 kDa), containing five low-spin heme centers of the B and C types, in a 1:4
      ratio. All the C-type hemes are in the same subunit (27 kDa). Three distinct
      redox transitions, at 235, 80, and -45 mV, were observed by visible redox
      titrations. The first involves one B- and one C-type hemes, and in the other two
      transitions one and two C-type hemes are involved, respectively. Spectroscopic
      data strongly suggest that the two hemes intervening in the last transition are
      in van der Waals contact, yielding a split Soret band. Electron paramagnetic
      resonance spectra of the oxidized complex show resonances of five low-spin ferric
      heme centers. Upon reduction with ascorbate, all these resonances vanish and a
      new one attributed to the last pair of hemes appears. A [3Fe-4S]1+/0 center
      copurifies with this complex, having a high reduction potential of +140 mV. No
      Rieske-type centers are detected in R. marinus and no effect is observed in the
      respiratory rates when the typical bc1 complex inhibitors are present, suggesting
      that such a complex is absent in R. marinus [Pereira et al. (1994) FEBS Lett.
      352, 327-330]. The newly isolated cytochrome bc complex has quinol:cytochrome c
      or high-potential iron-sulfur protein (HiPIP) oxidoreductase activity, being a
      functional analogue of the canonical bc1 complexes; i.e., it is the complex III
      in R. marinus. This complex plays a central role in this bacterium's electron
      transfer chain, coupling the electron transfer between the quinols reduced by the
      dehydrogenases and the HiPIP, the final electron donor to the terminal oxidases
      [Pereira, M. M., Carita, J. N., and Teixeira, M. (1999) Biochemistry 38, 1276
      1283].

PMID- 9930988
TI  - Membrane-bound electron transfer chain of the thermohalophilic bacterium
      Rhodothermus marinus: characterization of the iron-sulfur centers from the
      dehydrogenases and investigation of the high-potential iron-sulfur protein
      function by in vitro reconstitution of the respiratory chain.
AB  - Rhodothermus marinus, a thermohalophilic bacterium, has a unique electron
      transfer chain, containing, besides a cbb3 and a caa3 terminal oxidases, a novel
      cytochrome bc complex [Pereira, M. M., Carita, J. N., and Teixeira, M. (1999)
      Biochemistry 38, 1268-1275]. The membrane-bound iron-sulfur centers of this
      bacterium were studied by electron paramagnetic resonance (EPR) spectroscopy,
      leading to the identification of its main electron-transfer complexes. The
      resonances typical for the Rieske-type centers are not detected. Clusters S1 and
      S3 from succinate dehydrogenase were identified; interestingly, center S3 is
      shown to be present in two different conformations, with g values at 2.035,
      2.009, and 2.001 and at 2.025, 2.002, and 2.000. Upon addition of NADH and
      dithionite, EPR signals assigned to resonances characteristic of binuclear and
      tetranuclear clusters develop and are attributed to the iron-sulfur centers of
      complexes I and II. A high-potential iron-sulfur protein- (HiPIP-) type center
      previously detected in the membranes of this bacterium [Pereira et al. (1994)
      FEBS Lett. 352, 327-330] is shown to belong indeed to a canonical HiPIP. This
      protein was purified and extensively characterized. It is a small water-soluble
      protein of approximately 10 kDa, containing a single [4Fe-4S]3+/2+ cluster. The
      reduction potential, determined by EPR redox titrations in intact and detergent
      solubilized membranes as well as by cyclic voltammetry in solution, has a pH
      independent value of 260 +/- 20 mV, in the range 6-9. In vitro reconstitution of
      the R. marinus electron-transfer chain shows that the HiPIP plays a fundamental
      role in the chain, as the electron shuttle between R. marinus cytochrome bc
      complex and the caa3 terminal oxidase, being thus simultaneously identified a
      HiPIP reductase and a HiPIP oxidase.

PMID- 9930989
TI  - Studying low-density lipoprotein-monoclonal antibody complexes using dynamic
      laser light scattering and analytical ultracentrifugation.
AB  - Monoclonal antibody complexes have proven very useful in the study of low-density
      lipoproteins (LDLs). Thus, complexes composed of two different monoclonal
      antibodies, selected from a panel of 11 different antibodies, and LDL have been
      employed to map apolipoprotein B (apoB) on the surface of the LDL. In this way,
      apoB was found to surround the LDL as a ribbon with a bow [Chatterton, J. E., et
      al. (1995) J. Lipid Res. 36, 2027-2037]. Moreover, monoclonal MB19, which
      recognizes a polymorphic site, has been employed to quantitate the two different
      allelic forms of apoB found on LDL in human sera, and in this way, we assessed
      the effect of most of the known common polymorphisms of this protein as well as
      detected the depletion of the normal allele product in two forms of familial
      defective apoB-100 [Chatterton, J. E., et al. (1995) Biochemistry 34, 9571-9580;
      Pullinger, C. R., et al. (1995) J. Clin. Invest. 95, 1225-1234]. In this paper,
      these studies have been extended by examining by dynamic light scattering and
      sedimentation velocity techniques the complexes formed with only one antibody,
      and complexes formed using two antibodies. Our data show that the largest complex
      formed with a single monoclonal antibody was that of an LDL dimer; no larger,
      nonspecific complexes were present. With two antibodies, a variety of complexes
      were seen. Thus, monoclonal antibodies MB47 and 4G3, which bound about 55 degrees
      apart, formed a very stable dimer. Monoclonal antibodies MB47 and 2D8, which
      bound 136 degrees apart, formed a very stable tetramer, with four LDLs held
      together in probably a circular structure with four monoclonal antibodies.
      Finally, monoclonal antibodies 2D8 and 1D1, which bound 86 degrees apart,
      probably formed a less stable LDL tetramer, held together by three to four
      monoclonal antibodies. A rationale for these structures is discussed, as well as
      the biological relevance of these complexes.

PMID- 9930990
TI  - Delineation of two functionally distinct gammaPDE binding sites on the bovine
      retinal cGMP phosphodiesterase by a mutant gammaPDE subunit.
AB  - The gamma subunit of the retinal cGMP phosphodiesterase (gammaPDE) acts as an
      inhibitor of phosphodiesterase (PDE) catalytic activity and mediates enzyme
      regulation by the alpha subunit of the GTP-binding protein transducin (alphaT).
      In this work, we describe a full length, doubly point-mutated gamma subunit,
      C68S, Y84C gammaPDE, which binds to PDE with increased affinity but has a
      decreased ability to inhibit the enzyme. Fluorescence studies monitoring the
      competition between wild-type gammaPDE and the C68S, Y84C gammaPDE mutant suggest
      that the mutant gammaPDE binds with high affinity to only half of the total sites
      occupied by wild-type gammaPDE. Competition studies between wild-type gammaPDE
      and the mutant further suggest that the wild-type protein is able to fully
      inhibit PDE activity even when the mutant gammaPDE occupies its high-affinity
      binding site on PDE. Taken together, our findings are consistent with a model in
      which there are two distinguishable binding sites for gammaPDE on the PDE enzyme
      but that only one of the two sites mediates PDE inhibition.

PMID- 9930991
TI  - Overexpression and functional characterization of kinin receptors reveal subtype
      specific phosphorylation.
AB  - G protein-coupled receptors such as the receptors for bradykinin are present in
      low copy numbers in most natural cells. To overcome the problems associated with
      the analysis of these receptors at the protein level, we used highly efficient
      expression systems such as the baculovirus/insect cell system. However, the
      structural and functional statuses of recombinant receptors have often remained
      elusive. We have expressed the two types of human kinin receptors, B1 and B2, in
      Sf9 cells. Both receptors are found on the surface of infected cells where they
      display the same pharmacological profiles as their cognate receptors of native
      cells. The functional analysis of kinin receptors coupled to the intracellular
      signaling pathways of Sf9 cells revealed differential patterns of ligand-induced
      phosphorylation for the two kinin receptors. The B1 receptor failed to undergo
      ligand-induced phosphorylation. However the B2 receptor showed selective
      phosphorylation of a minor 38 kDa band and lack of phosphorylation of a dominant
      33 kDa band, indicating that only a fraction of the receptor protein is
      functionally linked to the kinase pathway. A striking discrepancy between the
      number of binding sites and the amount of receptor protein per cell (molar ratio
      of 1:20 to 1:1000) indicated that a significant portion of kinin receptors is
      associated with the intracellular compartments of Sf9 cells. Pulse-chase and
      immunoprecipitation experiments demonstrated that the heterogeneity of
      recombinant receptors is not due to proteolytic processing but likely reflects
      incomplete or lacking N-glycosylation. We conclude that the baculovirus/Sf9
      system is suitable for the recombinant expression and functional analysis of
      kinin receptors though limitations of the system have to be considered.

PMID- 9930992
TI  - Role of carboxyl-terminal charges on S-modulin membrane affinity and inhibition
      of rhodopsin phosphorylation.
AB  - S-Modulin shows a higher affinity for urea-stripped frog rod outer segment
      membranes than s26 (a cone homologue of S-modulin). NaCl at a concentration of
      several hundred millimolar reduced the membrane affinity of S-modulin to the s26
      level. Chimeric S-modulin and s26 whose respective 23 and 29 amino acids at the
      carboxyl terminus were swapped showed membrane affinites similar to those of s26
      and S-modulin, respectively. The membrane affinity of an S-modulin mutant lacking
      C-terminal positive charges was reduced to the s26 level, while another S-modulin
      mutant lacking C-terminal negative charges has a higher membrane affinity than
      wild-type S-modulin. When the molar ratio of recombinant S-modulins to rhodopsin
      is 0.5, there was no large difference in the inhibition efficiency. However, S
      modulin and mutants with high membrane affinities inhibit rhodopsin
      phosphorylation more efficiently than s26 and mutants with low membrane
      affinities at the molar ratio of 0.1. These results indicate that the C-terminal
      positive charges of these Ca2+-binding proteins enhance the membrane affinity and
      the inhibitory effect on rhodopsin phosphorylation by increasing the
      concentration of S-modulin on the membrane.

PMID- 9930993
TI  - Spontaneous propeptide processing of mini-stromelysin-1 mutants blocked by APMA
      ((4-Aminophenyl)mercuric acetate).
AB  - Human stromelysin-1 (SL-1) is a member of the stromelysin subfamily of matrix
      metalloproteinases (MMPs). The MMPs play a major role in the degradation of the
      extracellular matrix (ECM) during normal and pathological conditions. SL-1 like
      the other MMPs can be activated in vitro by the stepwise removal of the
      propeptide that contains a single unpaired cysteine which coordinates the active
      site zinc. Other residues in the propeptide also play a role in maintaining the
      latency of the enzymes. Deletion mutants and single-site amino acid replacements
      within the propeptide of a carboxyl-terminally truncated stromelysin-1 (mini-SL
      1) were constructed and expressed in Escherichia coli to further examine what
      amino acids within the propeptide of SL-1 are important for maintaining latency.
      While the natural enzyme displayed some limited tendency to spontaneously
      (autolytically) convert to lower Mr in a stepwise manner and finally to the fully
      processed form, all of the truncation mutants of more than 19 amino acids
      generated in E. coli showed greatly accelerated self-cleavage indicative of
      diminished stability and/or resistance to proteolysis of the residual propeptide.
      Mutant Delta63 as well as other mutants in which most of the propeptide had been
      deleted no longer responded to exposure to the organomercurial APMA by
      accelerated autolytic processing. Rather, APMA inhibited the autolytic processing
      in these mutants, further confirming the complexity of the action of this
      organomercurial in the activation of pro-MMPs.

PMID- 9930994
TI  - Effects of the E177K mutation in D-amino acid transaminase. Studies on an
      essential coenzyme anchoring group that contributes to stereochemical fidelity.
AB  - D-Amino acid transaminase is a bacterial enzyme that uses pyridoxal phosphate
      (PLP) as a cofactor to catalyze the conversion of D-amino acids into their
      corresponding alpha-keto acids. This enzyme has already been established as a
      target for novel antibacterial agents through suicide inactivation by a number of
      compounds. To improve their potency and specificity, the detailed enzyme
      mechanism, especially the role of its PLP cofactor, is under investigation. Many
      PLP-dependent transaminases have a negatively charged amino acid residue forming
      a salt-bridge with the pyridine nitrogen of its cofactor that promotes its
      protonation to stabilize the formation of a ketimine intermediate, which is
      subsequently hydrolyzed in the normal transaminase reaction pathway. However,
      alanine racemase has a positively charged arginine held rigidly in place by an
      extensive hydrogen bond network that may destabilize the ketimine intermediate,
      and make it too short-lived for a transaminase type of hydrolysis to occur. To
      test this hypothesis, we changed Glu-177 into a titratable, positively charged
      lysine (E177K). The crystal structure of this mutant shows that the positive
      charge of the newly introduced lysine side chain points away from the nitrogen of
      the cofactor, which may be due to electrostatic repulsions not being overcome by
      a hydrogen bond network such as found in alanine racemase. This mutation makes
      the active site more accessible, as exemplified by both biochemical and
      crystallographic data: CD measurements indicated a change in the microenvironment
      of the protein, some SH groups become more easily titratable, and at pH 9.0 the
      PMP peak appeared around 315 nm rather than at 330 nm. The ability of this mutant
      to convert L-alanine into D-alanine increased about 10-fold compared to wild-type
      and to about the same extent as found with other active site mutants. On the
      other hand, the specific activity of the E177K mutant decreased more than 1000
      fold compared to wild-type. Furthermore, titration with L-alanine resulted in the
      appearance of an enzyme-substrate quinonoid intermediate absorbing around 500 nm,
      which is not observed with usual substrates or with the wild-type enzyme in the
      presence of L-alanine. The results overall indicate the importance of charged
      amino acid side chains relative to the coenzyme to maintain high catalytic
      efficiency.

PMID- 9930995
TI  - Urea-induced unfolding and conformational stability of 3-isopropylmalate
      dehydrogenase from the Thermophile thermus thermophilus and its mesophilic
      counterpart from Escherichia coli.
AB  - To reveal the basis of the thermal stability of 3-isopropylmalate dehydrogenase
      (IPMDH) from an extreme thermophile, Thermus thermophilus, urea-induced unfolding
      of the enzyme and of its mesophilic counterpart from Escherichia coli has been
      studied. The urea-induced equilibrium unfolding of T. thermophilus and E. coli
      IPMDHs at 27 degreesC was monitored by measuring the changes in far-UV CD,
      intrinsic fluorescence, anilinonaphthalenesulfonic acid (ANS) binding, and
      catalytic activity in the presence of nonionic detergent Tween 20. For both
      enzymes, the spectral methods revealed a biphasic unfolding transition. The first
      transition was protein concentration-independent, whereas the second was protein
      concentration-dependent for both enzymes. The observation suggested a three-state
      unfolding mechanism with a dimeric intermediate. However, the intermediates of
      the E. coli and the T. thermophilus IPMDHs seemed to be different from each
      other. The intermediate of the E. coli IPMDH lost its secondary and tertiary
      structure more than that of the thermophilic enzyme. E. coli IPMDH lost enzymatic
      activity through the transition from the native to the intermediate state, though
      the intermediate of the T. thermophilus enzyme was still active. The unfolding
      process of E. coli IPMDH can be explained by a sequential unfolding of individual
      folding domains, while there is only a small structural perturbation in the
      intermediate of T. thermophilus IPMDH. The higher thermal stability of T.
      thermophilus IPMDH can be attributed to the increase in the extent of interaction
      inside the first domain which unfolded prior to the unfolding of the whole
      molecular structure in E. coli IPMDH.

PMID- 9930996
TI  - Chromatin hyperacetylation abrogates vitamin D-mediated transcriptional
      upregulation of the tissue-specific osteocalcin gene in vivo.
AB  - Cells expressing the bone-specific osteocalcin (OC) gene exhibit two DNase I
      hypersensitive sites within the proximal (nt -170 to -70) and distal (nt -600 to 
      400) promoter. These sites overlap elements that independently or in combination
      contribute to basal and vitamin D-stimulated OC gene transcription. Here we
      address mechanisms that participate in control of chromatin remodelling at these
      sites. By applying nuclease digestion and indirect end-labeling or by combining
      intranuclear footprinting and ligation-mediated PCR, we investigated the effects
      of nuclear protein hyperacetylation on both chromatin organization and
      transcriptional activation of the OC gene in bone-derived cells. We report that
      chromatin hyperacetylation blocks vitamin D stimulation of OC transcription and
      prevents a key transition in the chromatin structure of the OC gene which is
      required for formation of the distal DNase I hypersensitive site. This transition
      involves interaction of sequence-specific nuclear factors and may be required for
      the ligand-dependent binding of the vitamin D receptor complex, which results in
      transcriptional enhancement.

PMID- 9930997
TI  - Mapping of subunit-subunit contact surfaces on the beta subunit of Escherichia
      coli RNA polymerase.
AB  - The RNA polymerase core enzyme of Escherichia coli is composed of 2alpha, 1beta,
      and 1beta' subunits. Previously we mapped the alpha-alpha, alpha-beta, and alpha
      beta' contact sites on the alpha subunit. Here we analyzed the alpha subunit
      contact sites on the beta subunit by using various experimental approaches: (i)
      comparison of the proteolytic cleavage map between the unassembled free beta
      subunit and the alpha2 beta complex; (ii) analysis of the binary complex
      formation between His6-tagged intact alpha subunit and various truncated beta
      fragments; and (iii) analysis of the complex formation between the alpha subunit
      and various His6-tagged beta fragments. The results altogether indicate that two
      regions of the beta subunit are involved in the full activity of alpha binding,
      that is, the primary contact site between residues 737 and 904 and the secondary
      region with assembly control activity downstream from residue 1138. All of the
      alpha subunit-beta fragment binary complexes identified in this study were found
      to bind beta' subunit and form pseudo-core complexes, indicating that the regions
      of beta involved in alpha subunit contact also participate in interaction with
      the beta' subunit.

PMID- 9930998
TI  - Phosphatidylethanolamine modulates Ca-ATPase function and dynamics.
AB  - Phospholipids containing phosphoethanolamine (PE) headgroups within biological
      membranes have been suggested to be important with respect to the functional
      regulation of membrane proteins, including the Ca-ATPase in sarcoplasmic
      reticulum (SR). To investigate the role of PE headgroups in modulating the
      catalytic activity of the Ca-ATPase, we have reconstituted the Ca-ATPase into
      unilamellar liposomes containing defined amounts of
      dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC).
      The enzymatic activity of the Ca-ATPase progressively increases upon
      incorporation of increasing amounts of PE into reconstituted vesicles, and
      approaches that characteristic of native SR membranes. To identify structural
      changes that correlate with enzyme activation, we have used frequency-domain
      phosphorescence spectroscopy to measure the rotational dynamics of erythrosin
      isothiocyanate covalently bound to Lys464 in the phosphorylation domain of the Ca
      ATPase. Progressive increases in the rotational dynamics of the phosphorylation
      domain result from the incorporation of increasing amounts of DOPE, and correlate
      with enhanced enzymatic function. These results suggest that PE headgroups induce
      dynamic structural rearrangements involving the phosphorylation domain that
      modify the rates of nucleotide utilization. In contrast, no changes in the
      rotational dynamics of the lipid acyl chains are observed irrespective of the PE
      content. Therefore, the enhanced ATP hydrolytic activity associated with the
      incorporation of DOPE into these proteoliposomes is the result of specific
      noncovalent interactions involving PE phospholipid headgroups and the Ca-ATPase.

PMID- 9930999
TI  - Nonspecific weak actomyosin interactions: relocation of charged residues in
      subdomain 1 of actin does not alter actomyosin function.
AB  - Yeast actin mutants with relocated charged residues within subdomain 1 were
      constructed so we could investigate the functional importance of individual
      clusters of acidic residues in mediating actomyosin weak-binding states in the
      cross-bridge cycle. Past studies have established a functional role for three
      distinct pairs of charged residues within this region of yeast actin (D2/E4,
      D24/D25, and E99/E100); the loss of any one of these pairs resulted in the same
      impairment in weak actomyosin interaction and in its function. However, the
      specificity of myosin interaction with these sites has not yet been addressed. To
      investigate this, we made and analyzed two new actin mutants, 4Ac/D24A/D25A and
      4Ac/E99A/E100A. In these mutants, the acidic residues of the D24/D25 or E99/E100
      sites were replaced with uncharged residues (alanines) and a pair of acidic
      residues was inserted at the N-terminus, maintaining the overall charge density
      of subdomain 1. Using the in vitro motility assays, we found that the sliding and
      force generation properties of these mutant actins were identical to those of
      wild-type actin. Similarly, actin-activated ATPase activities of the mutant and
      wild-type actins were also indistinguishable. Additionally, the binding of S1 to
      these mutant actins in the presence of ATP was similar to that of wild-type
      actin. These results show that relocation of charged residues in subdomain 1 of
      actin does not affect the weak actomyosin interactions and actomyosin function.

PMID- 9931000
TI  - Modification of ribonuclease T1 specificity by random mutagenesis of the
      substrate binding segment.
AB  - Attempts to modify the guanine specificity of ribonuclease T1 (RNase T1) by
      rationally designed amino acid substitutions failed so far. Therefore, we applied
      a semirational approach by randomizing the guanine binding site. A combinatorial
      library of approximately 1.6 million RNase T1 variants containing permutations of
      6 amino acid positions within the recognition loop was screened on RNase
      indicator plates. The specificity profiles of 180 individual clones showing RNase
      activity revealed that variant K41S/N43W/N44H/Y45A/E46D (RNaseT1-8/3) exhibits an
      altered preference toward purine nucleotides. The ApC/GpC preference in the
      cleavage reaction of this variant was increased 4000-fold compared to wild-type.
      Synthesis experiments of dinucleoside monophosphates from cytidine and the
      corresponding 2'3'-cyclic diesters using the reverse reaction of the
      transesterification step showed a 7-fold higher ApC synthesis rate of RNase 8/3
      than wild-type, whereas the GpC synthesis rates for both enzymes were comparable.
      This study shows that site-directed random mutagenesis is a powerful additional
      tool in protein design in order to achieve new enzymatic specificities.

PMID- 9931001
TI  - Effects of core mutations on the folding of a beta-sheet protein: implications
      for backbone organization in the I-state.
AB  - A series of core mutations were introduced into beta-strand segments of an
      immunoglobulin fold (the isolated first domain of CD2, CD2.d1) to examine their
      influence on the rapidly formed intermediate state (I-state) which transiently
      accumulates in the folding reaction [Parker, M. J., and Clarke, A. R. (1997)
      Biochemistry 36, 5786-5794]. The residue changes were chemically conservative,
      each representing the removal of one or two methylene groups from aliphatic side
      chains. Predictably, the mutations destabilize the folded state with respect to
      the unfolded state by about 1.1 +/- 0.7 kcal mol-1 per methylene group removed.
      However, when the folding reaction is dissected by transient kinetic analysis
      into its component steps, six out of the nine mutations lead to a stabilization
      of the I-state. The direction and magnitude of these effects on the global
      stability of the transient intermediate are well correlated with changes in
      secondary structure propensity occasioned by the substitutions. The results show
      that, although side chain interactions are extremely weak in this early phase of
      folding, the beta-strand conformation of the polypeptide chain is established. In
      the next phase of the reaction, the rate-limiting transition state is attained by
      the formation of a tightly localized hydrophobic nucleus which includes residues
      V30, I18, and V78. Interestingly, in almost all immunoglobulin domains of
      extracellular proteins, the latter pair are cysteine residues which form a
      disulfide bridge.

PMID- 9931002
TI  - Solution structure of Delta5-3-ketosteroid isomerase complexed with the steroid
      19-nortestosterone hemisuccinate 

PMID- 9931003
TI  - Identification of a guanylyl cyclase-activating protein-binding site within the
      catalytic domain of retinal guanylyl cyclase 1.
AB  - Regulation of cAMP and cGMP production is a fundamental step in a broad range of
      signal transduction systems, including phototransduction. To identify regions
      within photoreceptor guanylyl cyclase 1 (GC1) that interact with GC-activating
      proteins (GCAPs), we synthesized the intracellular fragment of GC1, residues 491
      1110, as a set of 15 amino acid long, partially overlapping peptides on the
      surface of individual pins arranged in a microtiter plate format. This pin assay
      identified 8 peptides derived from different regions of the GC1 intracellular
      domain that bind GCAPs. Peptide variants containing these sequences were
      synthesized as free peptides and tested for their ability to inhibit GC1
      stimulation by GCAPs. A free peptide,968GTFRMRHMPEVPVRIRIG, from the catalytic
      domain of GC1 was the strongest inhibitor of GCAP1/GCAP2-mediated activation. In
      native GC1, this polypeptide fragment is likely to form a loop between alpha
      helix 3 and beta-strand 4. When this region in GC1 was replaced by the
      corresponding sequence of GCAP-insensitive GC type A, GCAPs did not stimulate the
      GC1 mutant. The corresponding loops in related adenylyl cyclase (AC) are involved
      in the activating and inhibiting interactions with Gs alpha and Gi alpha,
      respectively. Thus, despite interacting with different activating proteins, both
      AC and GC activity may be modulated through their respective regions within
      catalytic domains.

PMID- 9931004
TI  - Allosteric dominance in carbamoyl phosphate synthetase.
AB  - A linked-function analysis of the allosteric responsiveness of carbamoyl
      phosphate synthetase (CPS) from E. coli was performed by following the ATP
      synthesis reaction at low carbamoyl phosphate concentration. All three allosteric
      ligands, ornithine, UMP, and IMP, act by modifying the affinity of CPS for the
      substrate MgADP. Individually ornithine strongly promotes, and UMP strongly
      antagonizes, the binding of MgADP. IMP causes only a slight inhibition at 25
      degreesC. When both ornithine and UMP were varied, models which presume a
      mutually exclusive binding relationship between these ligands do not fit the data
      as well as does one which allows both ligands (and substrate) to bind
      simultaneously. The same result was obtained with ornithine and IMP. By contrast,
      the actions of UMP and IMP together must be explained with a competitive model,
      consistent with previous reports that UMP and IMP bind to the same site. When
      ornithine is bound to the enzyme, its activation dominates the effects when
      either UMP or IMP is also bound. The relationship of this observation to the
      structure of CPS is discussed.

PMID- 9931006
TI  - Conformational flexibility of a ubiquitin conjugation enzyme (E2).
AB  - Ubiquitination plays important roles in a variety of biological processes, such
      as DNA repair, cell cycle regulation, and p53-dependent processes. Despite
      intensive studies in ubiquitination, the mechanism of substrate recognition is
      still not well understood. Each E2 has its own substrate specificity, yet
      substrate proteins recognized by each E2 are highly diverse. To better understand
      how E2 proteins confer both substrate specificity and diversity, we have studied
      conformational flexibility of an E2, UBC9, using nuclear magnetic resonance 15N
      relaxation and hydrogen-deuterium exchange measurements. Two regions in human
      UBC9 show higher mobility over a wide range of time scales. Combined with
      previous biochemical studies, both regions are likely to be important for protein
      protein recognition in the ubiquitin pathway. The region near the N-terminus may
      be important for interactions with the E1-UBL1 conjugate. The region near the C
      terminus, which undergoes conformational exchange may be important for substrate
      binding and catalytic activity. Since E2 enzymes share high homology in primary
      sequences and three-dimensional structures, the conformational flexibility of
      UBC9 may represent a general feature of E2 enzymes. This study provides a new
      perspective for further studies of protein-protein recognition in ubiquitination.

PMID- 9931005
TI  - Solution structure and dynamics of the CX3C chemokine domain of fractalkine and
      its interaction with an N-terminal fragment of CX3CR1.
AB  - Fractalkine, a novel CX3C chemokine, is unusual because of both its membrane
      associated structure and its direct role in cell adhesion. We have solved the
      solution structure of the chemokine domain of fractalkine (residues 1-76) by
      heteronuclear NMR methods. The 20 lowest energy structures in the ensemble have
      an average backbone rmsd of 0.43 A, excluding the termini. In contrast to many
      other chemokines which form homodimers, fractalkine's chemokine module is
      monomeric. Comparison of the structure to CC and CXC chemokines reveals
      interesting differences which are likely to be relevant to receptor binding.
      These include a bulge formed by the CX3C motif, the relative orientation of the N
      terminus and 30's loop (residues 30-38), and the conformation of the N-loop
      (residues 9-19). 15N backbone relaxation experiments indicate that these same
      regions of the protein are dynamic. We also titrated 15N-labeled protein with a
      peptide from the N-terminus of the receptor CX3CR1 and confirmed that this region
      of the receptor contacts the fractalkine chemokine domain. Interestingly, the
      binding site maps roughly to the regions of greatest flexibility and structural
      variability. Together, these data provide a first glimpse of how fractalkine
      interacts with its receptor and should help guide mutagenesis studies to further
      elucidate the molecular details of binding and signaling through CX3CR1.

PMID- 9931007
TI  - Functional roles of the conserved aromatic amino acid residues at position 108
      (motif IV) and position 196 (motif VIII) in base flipping and catalysis by the N6
      adenine DNA methyltransferase from Thermus aquaticus.
AB  - The DNA methyltransferase (Mtase) from Thermus aquaticus (M.TaqI) catalyzes the
      transfer of the activated methyl group of S-adenosyl-L-methionine to the N6
      position of adenine within the double-stranded DNA sequence 5'-TCGA-3'. To
      achieve catalysis M.TaqI flips the target adenine out of the DNA helix. On the
      basis of the three-dimensional structure of M.TaqI in complex with the cofactor
      and its structural homology to the C5-cytosine DNA Mtase from Haemophilus
      haemolyticus, Tyr 108 and Phe 196 were suggested to interact with the
      extrahelical adenine. The functional roles of these two aromatic amino acid
      residues in M.TaqI were investigated by mutational analysis. The obtained mutant
      Mtases were analyzed in an improved kinetic assay, and their ability to flip the
      target base was studied in a fluorescence-based assay using a duplex
      oligodeoxynucleotide containing the fluorescent base analogue 2-aminopurine at
      the target position. While the mutant Mtases containing the aromatic amino acid
      Trp at position 108 or 196 (Y108W and F196W) showed almost wild-type catalytic
      activity, the mutant Mtases with the nonaromatic amino acid Ala (Y108A and F196A)
      had a strongly reduced catalytic constant. Y108A was still able to flip the
      target base, whereas F196A was strongly impaired in base flipping. These results
      indicate that Phe 196 is important for stabilizing the extrahelical target
      adenine and suggest that Tyr 108 is involved in placing the extrahelical target
      base in an optimal position for methyl group transfer. Since both aromatic amino
      acids belong to the conserved motifs IV and XIII found in N6-adenine and N4
      cytosine DNA Mtases as well as in N6-adenine RNA Mtases, a similar function of
      aromatic amino acid residues within these motifs is expected for the different
      Mtases.

PMID- 9931008
TI  - Time-resolved monitoring of electrogenic Na+-Ca2+ exchange in the isolated
      cardiac sarcolemma vesicles by using a rapid-response fluorescent probe.
AB  - As a major Ca exit system in myocytes, the electrogenic Na+-Ca2+ exchange is
      exposed to rapid changes of regulatory factors (e.g., cytosolic Ca) during the
      excitation-contraction coupling. The dynamic aspects of the exchanger response to
      regulatory factors have not been resolved in the past due to technical
      limitations. Here, we describe stopped-flow protocols for monitoring the
      electrogenic activity of Na+-Ca2+ exchange in cardiac sarcolemma vesicles by
      using a rapid-response voltage-sensitive dye Merocyanine-540 (M540). The M540
      signal of Nao-dependent Ca efflux is generated by mixing the Ca-loaded vesicles
      with Na buffer, yielding 160 mM extravesicular Na and 6 microM Cafree. This
      signal is inhibited by a cyclic peptide blocker (FRCRCFa), by a Ca ionophore
      (ionomycin), or by an electrogenic uncoupler (valinomycin or FCCP). The M540
      signal of Nao-dependent Ca efflux shows a rapid pre-steady-state burst (210 s-1),
      followed by slow steady-state phase (</=5 s-1). Extravesicular (cytosolic) Ni
      inhibits both phases with an IC50 of 0.80 +/- 0.24 mM. At an extravesicular pH of
      6.0, the Nao-dependent Ca efflux is able to generate the M540 signal, thereby
      supporting the idea that the stoichiometry of Na+-Ca2+ exchange is not altered at
      low pH [Khanashvili, D., et al. (1995) Biochemistry 34, 10290-10297]. The M540
      signal of Nao-dependent Ca efflux is lost when the extravesicular Cafree
      concentration drops to 0.2 microM. This effect cannot be explained by a lack of
      Ca access to extravesicular (cytosolic) transport sites, because the reaction of
      Nao-dependent Ca efflux utilizes intravesicular Ca as a substrate. These data
      suggest that in sarcolemma vesicles a regulatory cytosolic Ca site controls the
      exchanger activity. The properties of this putative regulatory site do not
      resemble the properties of the "slow" Ca regulatory mode, observed in
      electrophysiological studies. Under saturating ionic conditions, the Nao
      dependent Ca efflux generates the initial rates of 21 mV/ms in the vesicles with
      a diameter of 3000-5000 A. If a site density of 300-400 exchangers/micrometer2
      and a vesicular surface of 0.5 micrometer2 are assumed, each vesicle may contain
      150-200 exchanger molecules with a maximal turnover rate of 4000-5000 s-1. This
      upper limit for turnover (no matter what the site density is) may put
      considerable restrictions on the exchanger capacity to mediate Ca entry in the
      cell under physiologically related conditions.

PMID- 9931009
TI  - Calcium-dependent and -independent interactions of the calmodulin-binding domain
      of cyclic nucleotide phosphodiesterase with calmodulin.
AB  - The ubiquitous Ca2+-binding regulatory protein calmodulin (CaM) binds and
      activates a wide range of regulatory enzymes. The binding is usually dependent on
      the binding of Ca2+ to CaM; however, some target proteins interact with CaM in a
      calcium-independent manner. In this work, we have studied the interactions
      between CaM and a 20-residue synthetic peptide encompassing the major calmodulin
      binding domain of cyclic nucleotide phosphodiesterase (PDE1A2). The binding was
      studied in the absence and presence of Ca2+ by far-UV and near-UV circular
      dichroism, fluorescence, and infrared spectroscopy. In addition, two-dimensional
      heteronuclear NMR studies with 13C-methyl-Met-CaM and uniformly 15N-labeled CaM
      were performed. Competition assays with smooth muscle myosin light chain kinase
      revealed a Kd of 224 nM for peptide binding to Ca2+-CaM, while binding of the
      peptide to apo-CaM is weaker. The peptide binds with an alpha-helical structure
      to both lobes of Ca2+-saturated CaM, and the single Trp residue is firmly
      anchored into the C-terminal lobe of CaM. In contrast, the Trp residue plays a
      minor role in the binding to the apo-protein. Moreover, when bound to apo-CaM,
      the PDE peptide is only partially helical, and it interacts solely with the C
      terminal lobe of CaM. These results show that the Ca2+-induced activation of PDE
      involves a significant change in the structure and positioning of the CaM-bound
      PDE peptide domain.

PMID- 9931010
TI  - Analysis of amino and carboxy terminal GLUT-4 targeting motifs in 3T3-L1
      adipocytes using an endosomal ablation technique.
AB  - The targeting of the insulin-responsive glucose transporter, GLUT-4, to an
      intracellular compartment in adipocytes and muscle is one of the key features
      responsible for the unique insulin sensitivity of this transporter. Through
      expression of epitope-tagged GLUT-4 mutants in 3T3-L1 adipocytes, two motifs have
      been identified as playing a central role in GLUT-4 targeting: FQQI in the amino
      terminus and a di-leucine motif in the carboxy terminus. The goal of this study
      was to explore the role of these targeting motifs in the intracellular sorting of
      GLUT-4 using the Tf-HRP ablation technique. This technique provides a
      quantitative assessment of the amount of GLUT-4 located in recycling endosomes.
      In basal adipocytes, we find that approximately 40% of GLUT-4 is ablated
      following Tf-HRP loading. In contrast, here we demonstrate that the intracellular
      pool of a mutant in which F5 was mutated to A5 is localized to the recycling
      endosomal pathway, suggesting that the amino terminal FQQI motif functions in
      trafficking GLUT-4 from early endosomes. In contrast, GLUT-4 in which L489L490
      was mutated to A489A490 was localized predominantly to a nonablated compartment.
      These data imply a role for the di-leucine motif in sorting from a separate
      intracellular compartment, such as the TGN. Our findings are discussed within the
      context of a revised multicompartment model for GLUT-4 trafficking in adipocytes,
      in which mutations in either the FQQI or LL motifs result in the altered
      subcellular trafficking of GLUT-4 between multiple intracellular compartments.

PMID- 9931011
TI  - Walker mutations reveal loose relationship between catalytic and channel-gating
      activities of purified CFTR (cystic fibrosis transmembrane conductance
      regulator).
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an
      ATPase and as a chloride channel. It has been hypothesized, on the basis of
      electrophysiological findings, that the catalytic activity of CFTR is tightly
      coupled to the opening and closing of the channel gate. In the present study, to
      determine the structural basis for the ATPase activity of CFTR, we assessed the
      effect of mutations within the "Walker A" consensus motifs on ATP hydrolysis by
      the purified, intact protein. Mutation of the lysine residue in the "Walker A"
      motif of either the first nucleotide binding fold (CFTRK464A) or the second
      nucleotide binding fold (CFTRK1250A) inhibited the ATPase activity of the
      purified intact CFTR protein significantly, by greater than 50%. This finding
      suggests that the two nucleotide binding folds of CFTR are functioning
      cooperatively in catalysis. However, the rate of channel gating was only
      significantly inhibited in one of these purified mutants, CFTRK1250A, suggesting
      that ATPase activity may not be tightly coupled to channel gating as previously
      hypothesized.

PMID- 9931012
TI  - Beta-secondary and solvent deuterium kinetic isotope effects on catalysis by the
      Streptomyces R61 DD-peptidase: comparisons with a structurally similar class C
      beta-lactamase.
AB  - Beta-secondary and solvent deuterium kinetic isotope effects have been determined
      for the steady-state kinetic parameters V/K and V for turnover of a series of
      acyclic substrates by the DD-peptidase of Streptomyces R61 and the class C beta
      lactamase of Enterobacter cloacae P99. Although these enzymes are evolutionarily
      related and have very similar tertiary and active site structure, they are
      functionally very different-the former efficiently catalyzes the hydrolysis of
      beta-lactams but not acyclic peptides while vice versa applies to the latter. The
      measured kinetic isotope effects reveal both similarities and differences in the
      steady-state transition states for turnover of the various substrates by these
      enzymes. In most cases, inverse beta-secondary isotope effects were observed,
      reflecting typical acyl-transfer transition states. With one substrate, however,
      m-[[(phenylacetyl)glycyl]oxy]benzoic acid, isotope effects on V/K of very close
      to unity were obtained for both enzymes. These were interpreted in terms of
      acylation transition state conformations where the extent of beta-CH
      hyperconjugation was similar to that in the free substrate. Differences in
      deacylation transition states (V) between the two enzymes with this substrate
      were interpreted in terms of different acyl-enzyme conformations. Solvent
      deuterium kinetic isotope effects on V/K were uniformly small, some even inverse,
      for both enzymes and with all substrates tested. At face value, this suggests the
      counterintuitive conclusion that little proton transfer occurs in acylation
      transition states in all of these instances. Closer analysis, however, suggests
      that for ester and amide (and probably beta-lactam) substrates, this result
      probably arises from an increase in proton fractionation factors on substrate
      binding being offset by their decrease in the acylation transition state. The
      former event derives from proton rearrangement on substrate binding and the
      latter, presumably, from general acid/base catalysis. This result may be general
      to all beta-lactam-recognizing enzymes. The solvent isotope effects also suggest
      that, at least for the P99 beta-lactamase, the acylation transition state of a
      thioester substrate does not involve proton transfer. This can be interpreted in
      terms of the rate-determining breakdown of a tetrahedral intermediate where no
      protonation of the leaving thiolate is required. Deacylation transition states of
      both enzymes appear to involve significant proton transfer, presumably arising
      from general acid/base catalysis.

PMID- 9931014
TI  - Determination of the affinities between heterotrimeric G protein subunits and
      their phospholipase C-beta effectors.
AB  - Phosphatidylinositide-specific phospholipase C-betas play a key role in Ca2+
      signaling and are specifically activated by the alphaq family of heterotrimeric G
      proteins and as well as betagamma subunits. We have determined the affinity
      between Gbetagamma subunits and GTPgammaS and GDP-liganded Galphaq subunits on
      membrane surfaces, and their respective affinities to PLC-beta1, -beta2 and 
      beta3 effectors by fluorescence spectroscopy. We find that activation of Galphaq
      by GTPgammaS decreases its affinity for Gbetagamma subunits at least 36-fold
      compared to the GDP-liganded form, but increases its affinity for PLC-betas at
      least 40-200-fold depending on the PLC-beta isoform. The affinity of
      Galphaq(GTPgammaS) is similar for PLC-beta1 and -beta3 and 10-fold stronger for
      PLC-beta2, which corresponds to the reported relationship between the
      concentration of Galphaq(GTPgammaS) and PLC-beta activation on lipid bilayers. We
      find that a large portion of the PLC-beta-Galphaq association energy lies within
      the 400 residue C-terminal region of PLC-beta1 since truncating this region
      reduces its Galphaq affinity. In contrast, the isolated N-terminal region does
      not interact with Galphaq. Gbetagamma subunits interact with all three PLC-beta
      isotypes, but only showed strong binding to PLC-beta2, and activation of the
      three PLC-betas by Gbetagamma subunits parallels this behavior. We also tested
      the possibility that both Galphaq and Gbetagamma can simultaneously bind PLC
      beta2. Our data argue against simultaneous binding and show that Galphaq and
      Gbetagamma independently regulate this effector.

PMID- 9931013
TI  - Glucosylation of glycosylphosphatidylinositol membrane anchors: identification of
      uridine diphosphate-glucose as the direct donor for side chain modification in
      Toxoplasma gondii using carbohydrate analogues.
AB  - Toxoplasma gondii is an obligate intracellular parasite of the phylum apicomplexa
      and a common and often life-threatening opportunistic infection associated with
      AIDS. A family of parasite-specific glycosylphosphatidylinositols containing a
      novel glucosylated side chain has been shown to be highly immunogenic in humans
      (Striepen et al. (1997) J. Mol. Biol. 266, 797-813). In contrast to trypanosomes
      in T. gondii side chain modification takes place before addition to protein in
      the endoplasmic reticulum. The biosynthesis of these modifications was studied in
      an in vitro system prepared from hypotonically lysed T. gondii parasites.
      Radiolabeled glucose-containing glycosylphosphatidylinositol precursors were
      synthesized by T. gondii membrane preparations upon incubation with uridine
      diphosphate-[3H]glucose. Synthesis of glucosylated glycolipids took place only in
      the presence of exogenous uridine diphosphate-glucose and was stimulated by
      unlabeled uridine diphosphate-glucose in a dose-dependent manner. In contrast to
      glycosylphosphatidylinositol mannosylation, glucosylation was shown to be
      insensitive to amphomycin treatment. In addition, the glucose analogue 2-deoxy-D
      glucose was used to trace the glycosylphosphatidylinositol glucosylation pathway.
      Detailed analysis of glycolipids synthesized in vitro in the presence of UDP and
      GDP derivatives of D-glucose and 2-deoxy-D-glucose ruled out an involvement of
      dolichol phosphate-glucose and demonstrates direct transfer of glucose from
      uridine diphosphate-glucose.

PMID- 9931015
TI  - CCKA receptor activation stimulates p130(Cas) tyrosine phosphorylation,
      translocation, and association with Crk in rat pancreatic acinar cells.
AB  - p130(Cas) (Crk-associated substrate), because of its structure as an adapter
      protein, can interact when tyrosine-phosphorylated with a large number of
      cellular proteins and therefore be an important modulator of downstream signals.
      A number of growth factors, lipids, and a few G protein-coupled receptors can
      stimulate p130(Cas) tyrosine phosphorylation. Recent studies show that tyrosine
      phosohorylation of intracellular proteins by the hormone/neurotransmitter
      cholecystokinin (CCK) in rat pancreatic acinar cells may be an important
      signaling cascade. In this study, we show in rat dispersed pancreatic acini CCK-8
      rapidly stimulates tyrosine phosphorylation of p130(Cas), reaching a maximum (6.6
      +/- 1. 4)-fold increase with a half-maximal effect at 0.3 nM. Activation of
      protein kinase C by TPA or increases in [Ca2+]i by the calcium ionophore A23187
      stimulated p130(Cas) phosphorylation. Blockade of CCK increases in [Ca2+]i or PKC
      activity did not alter CCK-8-stimulated p130(Cas) phosphorylation; however,
      simultaneous blockage of both cascades caused a 50% inhibition. Partial
      inactivation by C. botulinum toxin of the small GTP-binding protein Rho caused a
      41 +/- 12% decrease in the CCK-stimulated p130(Cas) phosphorylation. Disruption
      of the actin cytoskeleton with cytochalasin D, but not the microtubule network
      with colchicine, completely inhibited CCK-8-stimulated p130(Cas) phosphorylation.
      Total p130(Cas) under basal conditions was largely localized (70 +/- 2%) in the
      membrane fraction, and stimulation with CCK-8 induced total p130(Cas)
      translocation from the cytosolic fraction. CCK stimulation also caused a (5 +/-
      1)-fold increase in p130(Cas) tyrosine phosphorylated in the plasma membrane.
      Treatment with tyrphostin B44 inhibited CCK-8-stimulated p130(Cas)
      phosphorylation, but it had no effect on p130(Cas) translocation. CCK-8 caused
      rapid formation of a p130(Cas)-Crk complex. In conclusion, our results
      demonstrate CCKA receptor activation causes rapid tyrosine phosphorylation of
      p130(Cas) through PLC-dependent and -independent mechanisms that require the
      participation of the small GTP-binding protein Rho and the integrity of the actin
      cytoskeleton, but not the microtubule network. Moreover, CCKA receptor activation
      causes translocation of p130(Cas) to the membrane and an increase in membrane
      tyrosine-phosphorylated p130(Cas). The translocation to the membrane does not
      require antecedent tyrosine phosphorylation. CCKA activation promotes the rapid
      formation of a p130(Cas)-Crk complex. These results suggest that p130(Cas) is
      likely an important modulator of downstream signals activated by CCK-8, possibly
      involved in regulating numerous cellular effects, such as effects on cell growth
      or cell shape.

PMID- 9931016
TI  - Glycosylation is essential for functional expression of a human brain ecto
      apyrase.
AB  - The importance of N-linked glycosylation for the function and oligomerization of
      an E-type ATPase was examined by using tunicamycin and peptide N-glycosidase F,
      two agents used to prevent and remove glycosylations, respectively. The cDNA
      encoding a human ecto-apyrase (HB6), predicted to have seven N-linked
      glycosylation sites, was transiently expressed in mammalian COS cells and the
      resulting membrane preparations were treated with peptide N-glycosidase F (PNGase
      F). PNGase-F caused a decrease in the apparent molecular weight of the protein
      (consistent with glycan removal) and a decrease in enzymatic activity over time.
      The ecto-apyrase was also expressed in the presence of tunicamycin, which
      completely prevented N-linked glycosylation, resulting in a nonglycosylated core
      protein devoid of ATP and ADP hydrolyzing activity. However, control and
      tunicamycin-treated cells expressed the enzyme to similar levels and
      localization. Interestingly, the quaternary structure of this E-type ATPase
      appears to be dependent upon the presence of glycan chains. The glycosylated ecto
      apyrase exists as a homodimer in situ as assessed by both size-exclusion
      chromatography of detergent-solubilized ecto-apyrase and cross-linking of
      membrane-bound ecto-apyrase, in contrast to the enzymatically deglycosylated ecto
      apyrase and the tunicamycin-treated ecto-apyrase. These results suggest that
      glycosylation is necessary for homooligomerization and nucleotide hydrolyzing
      activity, but not for expression and plasma membrane localization of the E-type
      ATPase. Similar results were obtained with another human ecto-apyrase, CD39,
      suggesting that the importance of glycosylation may be generalized to all
      membrane-bound E-type ATPases.

PMID- 9931017
TI  - Differential association of the pleckstrin homology domains of phospholipases C
      beta 1, C-beta 2, and C-delta 1 with lipid bilayers and the beta gamma subunits
      of heterotrimeric G proteins.
AB  - Pleckstrin homology (PH) domains are recognized in more than 100 different
      proteins, including mammalian phosphoinositide-specific phospholipase C (PLC)
      isozymes (isotypes beta, gamma, and delta). These structural motifs are thought
      to function as tethering devices linking their host proteins to membranes
      containing phosphoinositides or beta gamma subunits of heterotrimeric GTP binding
      (G) proteins. Although the PH domains of PLC-delta and PLC-gamma have been
      studied, the comparable domains of the beta isotypes have not. Here, we have
      measured the affinities of the isolated PH domains of PLC-beta 1 and -beta 2 (PH
      beta 1 and PH-beta 2, respectively) for lipid bilayers and G-beta gamma subunits.
      Like the intact enzymes, these PH domains bind to membrane surfaces composed of
      zwitterionic phosphatidylcholine with moderate affinity. Inclusion of the anionic
      lipid phosphatidylserine or phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and
      inclusion of G-beta gamma subunits had little affect on their membrane affinity.
      In contrast, binding of PLC-delta 1 or its PH domain was highly dependent on
      PI(4,5)P2. We also determined whether these domains laterally associate with G
      beta gamma subunits bound to membrane surfaces using fluorescence resonance
      energy transfer. Affinities for G-beta gamma were in the following order: PH-beta
      2 >/= PH-beta 1 > PH-delta 1; the affinities of the native enzyme were as
      follows: PLC-beta 2 >> PLC-delta 1 > PLC-beta 1. Thus, the PH domain of PLC-beta
      1 interacts with G-beta gamma in isolation, but not in the context of the native
      enzyme. By contrast, docking of the PH domain of PLC-beta2 with G-beta gamma is
      comparable to that of the full-length protein and may play a key role in G-beta
      gamma recognition.

PMID- 9931018
TI  - Thermal and pH-induced conformational changes of a beta-sheet protein monitored
      by infrared spectroscopy.
AB  - The stability of a lentil lectin, an all-beta protein, has been perturbed by
      changes in pH and temperature. In the pH interval 5.0 --> 10.0, the overall
      secondary structure does not undergo significant changes. However, if the
      individual components of the infrared amide I band are considered, changes in
      band components attributed to variations in beta-sheet and beta-turns cross
      interactions are detected. The combined effects of pH and temperature reveal that
      the protein is more compact at pH 7.5 with lower denaturation temperatures at pH
      5.0 or 10.0, indicating a less stable protein under those conditions. According
      to our results, the structural stability of the beta-sheet would depend not only
      on the intermolecular interactions among the strands but also on the conformation
      of the segments connecting these strands. The protein infrared band assignment
      has also been examined since the three-dimensional structure of the lentil lectin
      protein is known from X-ray diffraction studies. Two of the bands observed are
      attributed to beta-sheet. The one at 1620 cm-1, not affected if the medium is
      deuterated, is assigned to hairpins composed by two strands connected by a rigid
      turn whereas that located at 1633 cm-1 corresponds to strands associated by more
      flexible segments. The band appearing at 1645 cm-1 in H2O corresponds to the
      open, flexible loops that are connecting the beta-strands. The simplest
      assumption of the various secondary structure components having identical IR
      extinction coefficients is enough to provide IR-derived data that are in good
      agreement with the structure solved by X-ray diffraction.

PMID- 9931019
TI  - A chimeric inorganic pyrophosphatase derived from Escherichia coli and Thermus
      thermophilus has an increased thermostability.
AB  - Factors contributing to the thermostability of inorganic pyrophosphatase (PPase)
      were investigated by examining chimeric PPases from Escherichia coli and Thermus
      thermophilus (Tth). Two chimeric PPase genes, T1-135E (residues 1-135 from the N
      terminus are comprised of Tth PPase and residues 136-173 are derived from the C
      terminus of E. coli PPase) and T1-149E [residues 1-149 from the N terminus are
      from Tth PPase and the rest (150-175) are from E. coli PPase], were constructed
      by random chimeragenesis. After the genes were overexpressed in the E. coli
      BL21(DE3) strain and the expression products were purified, we compared the
      characteristics of these chimeric PPases with those of the parental PPases. We
      found that the two chimeras had higher activity than either parent PPase at the
      optimum temperature. We also examined thermal stability in terms of CD spectra,
      fluorescence spectra, and thermal changes in enzyme activity. The results
      revealed that the thermal stability of T1-149E is similar to that of Tth PPase,
      but T1-135E is much more stable. This suggests that the four residues that are
      different between T1-135E and T1-149E may be critical for thermostability between
      the two chimeras. By comparing the three-dimensional structures of Tth and E.
      coli PPases, we deduced that the following two factors may contribute to
      differences in thermostability. (1) Two residues (Thr138 and Ala141 in the Tth
      PPase and His140 and Asp143 in the E. coli PPase) in the vicinity of the trimer
      trimer interface were different. (2) The Ala144-Lys145 loop in the Tth PPase was
      deleted in the E. coli PPase and also in the T1-135E chimera. Therefore, we
      conclude that T1-135E was thermostabilized by these two factors, and also, the
      Tth PPase moiety may contribute to the structural integrity of the chimeric
      enzymes.

PMID- 9931020
TI  - N1-(5'-phosphoribosyl)adenosine-5'-monophosphate cyclohydrolase: purification and
      characterization of a unique metalloenzyme.
AB  - N1-(5'-Phosphoribosyl)adenosine-5'-monophosphate cyclohydrolase (HisI, PR-AMP
      cyclohydrolase) is a central enzyme in histidine biosynthesis catalyzing the
      hydrolysis of the N1-C6 bond of the purine substrate, a reaction unique to this
      pathway. A source of the recombinant monofunctional Methanococcus vannielii PR
      AMP cyclohydrolase has been developed, and the first characterization of a
      purified form of the enzyme is reported. The enzyme has a native molecular weight
      of 31 200 as determined by analytical ultracentrifugation that agrees with the
      molecular mass determined by gel filtration (34 kDa) and a subunit molecular
      weight of 15 486 based on MALDI-MS. An unusual characteristic of the protein is
      the complexity observed on SDS-PAGE, and N-terminal amino acid sequence analysis
      of all the isolated constituents confirms their origin as PR-AMP cyclohydrolase.
      A highly conserved region of the amino acid sequence is implicated in the self
      cleavage events of the protein and provides an explanation for the complexity of
      this protein. Bound to the enzyme is 1 equiv of Zn2+ that can be removed only by
      extended dialysis with 1,10-phenanthroline (Kd </= 10(-)9 M). Removal of the Zn2+
      correlates with the loss of enzyme activity. The enzyme is reversibly inhibited
      by inclusion of EDTA in the assay mixture, demonstrating that free Mg2+ (Ks = 4.9
      +/- 0.7 microM) is required for catalytic activity. Further evidence for a low
      affinity binding site is indicated by the inhibitory effects of exogenous Zn2+ on
      enzyme activity. The pH dependence of the PR-AMP cyclohydrolase activity shows a
      single titration event in the kcat/Km profile with a pKa of 7.3 that is
      consistent with the functional role of a metal site in catalysis. These data are
      discussed in the context of the mechanism of other nucleotide hydrolases.

PMID- 9931021
TI  - Kinetic mechanism of metallo-beta-lactamase L1 from Stenotrophomonas maltophilia.
AB  - The reaction of nitrocefin with metallo-beta-lactamase L1 from Stenotrophomonas
      maltophilia was studied using rapid-scan and stopped-flow ultraviolet-visible (UV
      vis) studies in an effort to discern the kinetic mechanism used by L1 to
      hydrolyze penicillins and cephalosporins. Rapid-scan and stopped-flow UV-vis
      studies of nitrocefin hydrolysis by L1 identified three species: (1) the
      substrate (nitrocefin) displayed an absorbance peak at 390 nm (epsilon = 11 500
      M(-1) cm(-1)) that decreased during the reaction with a rate constant of 170 +/-
      30 s(-1); (2) the product (hydrolyzed nitrocefin) displayed an absorbance peak at
      485 nm (epsilon = 17 420 M(-1) cm(-1)) that increased during the reaction with
      rate constant of 40 +/- 1 s(-1); and (3) an intermediate displayed an absorbance
      peak at 665 nm (epsilon = 32 000 M(-1) cm(-1)) that increased initially with a
      rate constant of 190 +/- 3 s(-1) and then decreased with a rate constant of 38 +/
      2 s(-1). Single-turnover experiments demonstrated that there were no pre-steady
      state bursts in the reaction of L1 with nitrocefin; moreover, the progress curves
      could be fit to a kinetic mechanism that includes the formation of a transient
      intermediate by using KINSIM and the rate constants given above. Progress curves
      from experiments conducted at different reaction conditions or with a different
      substrate could also be fit to the proposed kinetic mechanism. The evidence for
      the presence of an intermediate along with kinetic simulations supports a
      hydrolytic mechanism for L1 that involves an intermediate whose breakdown is rate
      determining.

PMID- 9931022
TI  - Dynamics of palmitic acid complexed with rat intestinal fatty acid binding
      protein.
AB  - Dynamics of palmitic acid (PA), isotopically enriched with 13C at the second,
      seventh, or terminal methyl position, were investigated by 13C NMR. Relaxation
      measurements were made on PA bound to recombinant rat intestinal fatty acid
      binding protein (I-FABP) at pH 5.5 and 23 degreesC, and, for comparison, on PA
      incorporated into 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (MPPC)
      micelles, and dissolved in methanol. The 13C relaxation data, T1, and steady
      state nuclear Overhauser effect (NOE) obtained at two different magnetic fields
      were interpreted using the model-free approach [Lipari, G., and Szabo, A. (1982)
      J. Am. Chem. Soc. 104, 4546-4559]. The overall rotational correlation time of the
      fatty acid.protein complex was 2.5 +/- 0.4 ns, which is substantially less than
      the value expected for the protein itself (>6 ns). Order parameters (S2), which
      are a measure of the amplitude of the internal motion of individual C-H vectors
      with respect to the PA molecule, while largest for C-2 and smallest for the
      methyl carbon, were relatively small (<0.4) in the protein complex. S2 values for
      given C-H vectors also were smaller for PA in the MPPC micelles and in methanol
      than in the protein complex. Correlation times reflective of the time scale of
      the internal motion of the C-H vectors were in all cases <60 ps. These results
      support the view that the fatty acid is not rigidly anchored within the I-FABP
      binding pocket, but rather has considerable freedom to move within the pocket.

PMID- 9931023
TI  - Arginine activity in the proton-motive photocycle of bacteriorhodopsin: solid
      state NMR studies of the wild-type and D85N proteins.
AB  - 15N solid-state NMR (SSNMR) spectra of guanidyl-15N-labeled bacteriorhodopsin
      (bR) show perturbation of an arginine residue upon deprotonation of the retinal
      Schiff base during the photocycle. At the epsilon position, an upfield shift of 4
      ppm is observed while the eta nitrogens develop a pair of 'wing' peaks separated
      by 24 ppm. Proton-driven spin diffusion between the two 'wing' peaks indicates
      that they arise from a single Arg residue. An unusually asymmetric environment
      for this residue is indicated by comparison with guanidyl-15N chemical shifts in
      a series of arginine model compounds. The 'wing' peaks are tentatively assigned
      to Arg-82 on the basis of the SSNMR investigations of the alkaline and neutral
      dark-adapted forms of the D85N bacteriorhodopsin mutant. Another, less asymmetric
      pair of eta signals, that is not affected by Schiff base deprotonation or D85
      mutation, is tentatively assigned to Arg-134. The results are discussed in
      relation to existing models of bR structure and function.

PMID- 9931024
TI  - Fluorescence energy transfer as a probe for tetraplex formation: the i-motif.
AB  - The secondary structure of cytosine-rich oligodeoxynucleotides has been
      investigated with fluorescent probes. Intramolecular folding of an
      oligonucleotide into an i-DNA motif led to fluorescence excitation energy
      transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine)
      covalently attached to the 5' and 3' ends of the DNA, respectively, provided that
      a suitable linker was chosen. The conjugation of the dyes to the oligonucleotide
      had an influence on the thermodynamics of i-motif formation as well as on the
      kinetics of folding. Intramolecular folding was demonstrated from the
      concentration independence of FRET over a wide concentration range. Folding of
      the oligonucleotide was confirmed by UV absorption melting experiments. The
      folding of the i-motif could be followed at concentrations as low as 50 pM.
      Fluorescence energy transfer can thus be used to reveal the formation of
      multistranded DNA structures.

PMID- 9931025
TI  - Site-directed mutagenesis of basic arginine residues 305 and 342 in the CP 43
      protein of photosystem II affects oxygen-evolving activity in Synechocystis 6803.
AB  - The intrinsic chlorophyll protein CP 43, a component of photosystem II (PS II) in
      higher plants, green algae, and cyanobacteria, is encoded by the psbC gene.
      Oligonucleotide-directed mutagenesis was employed to introduce mutations into a
      segment of psbC that encodes the large extrinsic loop E of CP 43 in the
      cyanobacterium Synechocystis 6803. Two mutations, R305S and R342S, each produced
      a strain with impaired photosystem II activity. The R305S mutant strain grew
      photoautotrophically at rates comparable to the control strain. Immunological
      analyses of a number of PSII components indicated that this mutant accumulated
      normal quantities of PSII proteins. However, this mutant evolved oxygen to only
      70% of control rates at saturating light intensities. Measurements of total
      variable fluorescence yield indicated that this mutant assembled approximately
      70% of the PSII centers found in the control strain. The R342S mutant failed to
      grow photoautotrophically and exhibited no capacity for oxygen evolution.
      However, when grown photoheterotrophically in medium containing both glucose and
      3-(3, 4-dichlorophenyl)-1,1-dimethylurea (DCMU), oxygen-evolving activity was
      observed in the R342S mutant, but at a low level of approximately 10% of the
      control rate. Immunological analysis of isolated thylakoid membranes from this
      mutant also indicated that this strain accumulated normal amounts of PSII core
      proteins. Total variable fluorescence yields for the R342S mutant indicated that
      it assembled a severely reduced number of fully functional PSII centers. R305S
      and R342S mutant strains exhibited, respectively, 2.7- and 4-fold increased
      sensitivity to photoinactivation. The fluorescence rise times for both mutants
      were comparable to the control when hydroxylamine was used as electron donor.
      However, both strains exhibited an increase (2.5- and 8-fold, respectively, for
      R305S and R342S) in fluorescence rise times with water as an electron donor.
      These results suggest that the mutations R305S and R342S each produce a defect
      associated with the oxygen-evolving complex of photosystem II. These are the
      first site-directed mutations in CP 43 to show such an effect.

PMID- 9931026
TI  - Comparing the rates and the activation parameters for the forward reaction
      between the triplet state of zinc cytochrome c and cupriplastocyanin and the back
      reaction between the zinc cytochrome c cation radical and cuproplastocyanin.
AB  - This is a comparative study of the photoinduced (so-called forward) electron
      transfer reaction 3Zncyt/pc(II) --> Zncyt+/pc(I), between the triplet state of
      zinc cytochrome c (3Zncyt) and cupriplastocyanin [pc(II)], and the thermal (so
      called back) electron-transfer reaction Zncyt+/pc(I) --> Zncyt/pc(II), between
      the cation (radical) of zinc cytochrome c (Zncyt+) and cuproplastocyanin [pc(I)],
      which follows it. Both reactions occur between associated (docked) reactants, and
      the respective unimolecular rate constants are kF and kB. Our previous studies
      showed that the forward reaction is gated by a rearrangement of the diprotein
      complex. Now we examine the back reaction and complare the two. We study the
      effects of temperature (in the range 273.3-302.9 K) and viscosity (in the range
      1.00-17.4 cP) on the rate constants and determine enthalpies (DeltaH), entropies
      (DeltaS), and free energies (DeltaG) of activation. We compare wild-type spinach
      plastocyanin, the single mutants Tyr83Leu and Glu59Lys, and the double mutant
      Glu59Lys/Glu60Gln. The rate constant kB for wild-type spinach plastocyanin and
      its mutants markedly depends on viscosity, an indication that the back reaction
      is also gated. The activation parameters DeltaH and DeltaS show that the forward
      and back reactions have similar mechanisms, involving a rearrangement of the
      diprotein complex from the initial binding configuration to the reactive
      configuration. The rearrangements of the complexes 3Zncyt/pc(II) and Zncyt+/pc(I)
      that gate their respective reactions are similar but not identical. Since the
      back reaction of all plastocyanin variants is faster than the forward reaction,
      the difference in free energy between the docking and the reactive configuration
      is smaller for the back reaction than for the forward reaction. This difference
      is explained by the change in the electrostatic potential on the plastocyanin
      surface as Cu(II) is reduced to Cu(I). It is the smaller DeltaH that makes DeltaG
      smaller for the back reaction than for the forward reaction.

PMID- 9931027
TI  - Biochemical differences between rat and human cytochrome P450c17 support the
      different steroidogenic needs of these two species.
AB  - Microsomal 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) catalyzes
      both the 17alpha-hydroxylase reaction required to produce cortisol, the major
      glucocorticoid in many animals, and the 17, 20-lyase activity required for the
      production of androgens in all animals. In rodents such as rat, which utilize
      corticosterone as the major glucocorticoid, P450c17 is expressed predominantly in
      the gonads, and is absent in the adrenal. In other species including humans,
      P450c17 is expressed in both adrenal and gonads and participates in both
      glucocorticoid and androgen production. Rat and human forms of P450c17 are 69%
      identical at the amino acid level. Based on the differences in physiological
      roles between P450c17 in these two species, it could be predicted that major
      differences would be observed in their hydroxylase activities. Contrary to this
      hypothesis, using partially purified, recombinant human and rat P450c17, we found
      that the most significant differences lie in their lyase activities. Lyase
      activities demonstrate that the rat enzyme favors Delta4 (progesterone)
      substrates while the human enzyme favors Delta5 (pregnenolone) substrates. This
      substrate preference is also observed in the ability of steroids to decrease
      uncoupled H2O2 production and to increase stability during turnover. Cytochrome
      b5, a microsomal electron-transfer protein, enhances lyase activities of rat and
      human P450c17. However, the most dramatic stimulatory effect is on the human HO
      PROG lyase activity. This enhancement of activities is not associated with
      electron transfer. These differences in biochemical properties between the two
      forms of P450c17 indicate that human P450c17 has evolved as an enzyme system that
      limits androgen production to the gonads where a favorable b5:P450c17 ratio
      exists. Even though orthologous forms of P450c17 are capable of catalyzing the
      same enzymatic activities, specific physiological requirements of each species
      ensure biochemical differences between these enzymes.

PMID- 9931028
TI  - Structure-based design of inhibitors specific for bacterial thymidylate synthase.
AB  - Thymidylate synthase is an attractive target for antiproliferative drug design
      because of its key role in the synthesis of DNA. As such, the enzyme has been
      widely targeted for anticancer applications. In principle, TS should also be a
      good target for drugs used to fight infectious disease. In practice, TS is highly
      conserved across species, and it has proven to be difficult to develop inhibitors
      that are selective for microbial TS enzymes over the human enzyme. Using the
      structure of TS from Lactobacillus casei in complex with the nonsubstrate
      analogue phenolphthalein, inhibitors were designed to take advantage of features
      of the bacterial enzyme that differ from those of the human enzyme. Upon
      synthesis and testing, these inhibitors were found to be up to 40-fold selective
      for the bacterial enzyme over the human enzyme. The crystal structures of two of
      these inhibitors in complex with TS suggested the design of further compounds.
      Subsequent synthesis and testing showed that these second-round compounds inhibit
      the bacterial enzyme at sub-micromolar concentrations, while the human enzyme was
      not inhibited at detectable levels (selectivities of 100-1000-fold or greater).
      Although these inhibitors share chemical similarities, X-ray crystal structures
      reveal that the analogues bind to the enzyme in substantially different
      orientations. Site-directed mutagenesis experiments suggest that the individual
      inhibitors may adopt multiple configurations in their complexes with TS.

PMID- 9931029
TI  - Interleukin 1 (IL-1) causes changes in lateral and rotational mobilities of IL-1
      type I receptors.
AB  - To investigate IL-1-dependent interactions of IL-1 type I (IL-1 RI) receptors on
      intact cells, lateral and rotational mobilities and detergent insolubility were
      investigated. Lateral mobility was measured by fluorescence photobleaching
      recovery, using a Cy3-modified, noncompetitive mAb specific for IL-1RI (M5) bound
      to wild-type IL-1 RI or mutant IL-1 RI with a truncated cytoplasmic tail.
      Addition of IL-1 causes significant reduction in the mobile fraction of wild-type
      IL-1 RI for two different transfected cell lines. For the mutant IL-1 RI, no
      significant decrease in response to IL-1 is observed, indicating that the missing
      cytoplasmic segment is involved in IL-1-dependent interactions of IL-1 RI that
      lead to reduced lateral mobility on the cell surface. The rotational mobility of
      IL-1 RI was assessed with phosphorescence anisotropy decay measurements using
      erythrosin-labeled M5. IL-1 decreases the rotational mobility of cell surface IL
      1 RI on the microsecond time scale and also increases the initial anisotropy,
      indicating loss in segmental motion. Measurements of resistance to solubilization
      by Triton X-100 showed that IL-1 binding increases the fraction of IL-1 RI
      sedimenting with cytoskeletal residues. The IL-1 receptor antagonist protein (IL
      1ra) causes partial effects in reducing rotational mobility and increasing
      detergent insolubility of M5-lableled IL-1 RI, indicating that this ligand causes
      structural changes in the presence of the dimerizing M5 mAb. These ligand
      dependent physical interactions of IL-1 RI on the cell surface may be related to
      signal initiation by this receptor.

PMID- 9931030
TI  - Comparison of the sequence-selective DNA binding by peptide dimers with covalent
      and noncovalent dimerization domains.
AB  - Sequence-specific DNA binding proteins generally consist of more than two DNA
      contacting regions to ensure the selectivity of recognition. The multiple DNA
      binding modules are connected either through the covalent linker or through the
      noncovalent dimerization domain. We have compared the DNA binding of peptide
      dimers with covalent and noncovalent dimerization domains to explore the
      potential advantage of each linkage on the sequence-specific DNA binding. Three
      sets of head-to-tail peptide dimers were synthesized by using the same basic
      region peptide to target the same DNA sequence; one dimer was assembled with a
      bridged biphenyl derivative as a covalent dimerization domain, and two other
      dimers were assembled with the cyclodextrin guest noncovalent dimerization
      domains. One of the noncovalent dimers was a heterodimer that consisted of
      cyclodextrin and guest peptides, while the other was a homodimer that consisted
      of peptides bearing both cyclodextrin and the guest molecule within the same
      chain. Both noncovalent dimers formed the specific DNA complexes within narrower
      ranges of peptide concentrations and showed higher sequence selectivity than the
      covalent dimer did. Among the three dimers, the noncovalent homodimer that can
      form an intramolecular inclusion complex showed the highest sequence selectivity.
      Because the noncovalent homodimer with the higher stability of the circular
      intramolecular inclusion complex exhibited the higher sequence selectivity, it
      was concluded that an equilibrium involving a conformational transition of a
      monomeric peptide effectively reduced the stability of its nonspecific binding
      complex, hence increasing the efficacy of cooperative dimer formation at the
      specific DNA sequence.

PMID- 9931031
TI  - Intramolecular chimeras of the p51 subunit between HIV-1 and FIV reverse
      transcriptases suggest a stabilizing function for the p66 subunit in the
      heterodimeric enzyme.
AB  - The human immunodeficiency virus (HIV) reverse transcriptase (RT) is a
      heterodimeric enzyme composed of a 66 kDa (p66) and a 51 kDa (p51) subunit.
      Recently we showed that p51 plays an important role in the conformation of p66
      within the HIV-1 RT heterodimer and hence appears to influence its catalytic
      activities [Amacker, M., and H ubscher, U. (1998) J. Mol. Biol. 278, 757-765].
      This was further investigated here via construction of three intramolecular
      chimeras of HIV-1 and FIV RTs. The first 25 and 112 amino acids of the N
      terminus, respectively, as well as the last 22 amino acids of the C terminus in
      the p51 subunit of HIV-1 RT were exchanged with the corresponding regions of the
      FIV RT and combined with the wild-type HIV-1 p66. Characterization of these
      chimeric RT heterodimers demonstrated significant biochemical differences in (i)
      DNA-dependent DNA synthesis, (ii) strand displacement DNA synthesis, and (iii)
      RNase H activity. Our results indicate that both the N and C termini of HIV-1 RT
      p51 appear to be important in stabilizing the RT heterodimer for enzymatic
      functions.

PMID- 9931032
TI  - Dissecting the role of acyltransferase domains of modular polyketide synthases in
      the choice and stereochemical fate of extender units.
AB  - Modular polyketide synthases (PKSs), such as the 6-deoxyerythronolide B synthase
      (DEBS), are large multifunctional enzyme complexes that are organized into
      modules, where each module carries the domains needed to catalyze the
      condensation of an extender unit onto a growing polyketide chain. Each module
      also dictates the stereochemistry of the chiral centers introduced into the
      backbone during the chain elongation process. Here we used domain mutagenesis to
      investigate the role of the acyl transferase (AT) domains of individual modules
      in the choice and stereochemical fate of extender units. Our results indicate
      that the AT domains of DEBS do not influence epimerization of the (2S)
      methylmalonyl-CoA extender units. Hence, stereochemical control of the methyl
      branched centers generated by DEBS most likely resides in the ketosynthase (KS)
      domains of the individual modules. In contrast, several recent studies have
      demonstrated that extender unit specificity can be altered by AT domain
      substitution. In some of these examples, the resulting polyketide was produced at
      considerably lower titers than the corresponding natural product. We analyzed one
      such attenuated mutant of DEBS, in which the methylmalonyl transferase domain of
      module 2 was replaced with a malonyl transferase domain. As reported earlier, the
      resulting PKS produced only small quantities of the expected desmethyl analogue
      of 6-deoxyerythronolide B. However, when the same hybrid module was placed as the
      terminal module in a truncated 2-module PKS, it produced nearly normal quantities
      of the expected desmethyl triketide lactone. These results illustrate the limits
      to modularity of these multifunctional enzymes. To dissect the role of specific
      amino acids in controlling AT substrate specificity, we exchanged several
      segments of amino acids between selected malonyl and methylmalonyl transferases,
      and found that a short (23-35 amino acid) C-terminal segment present in all AT
      domains is the principal determinant of their substrate specificity.
      Interestingly, its length and amino acid sequence vary considerably among the
      known AT domains. We therefore suggest that the choice of extender units by the
      PKS modules is influenced by a "hypervariable region", which could be manipulated
      via combinatorial mutagenesis to generate novel AT domains possessing relaxed or
      altered substrate specificity.

PMID- 9931035
TI  - Absorbing calcium.

PMID- 9931033
TI  - Site-directed mutagenesis of charged and potentially proton-carrying residues in
      the beta subunit of the proton-translocating nicotinamide nucleotide
      transhydrogenase from Escherichia coli. Characterization of the beta H91, beta
      D392, and beta K424 mutants.
AB  - Conserved and semiconserved acidic and basic residues of the beta subunit of the
      proton-pumping nicotinamide nucleotide transhydrogenase from Escherichia coli
      potentially involved in proton pumping were investigated. Out of 16 charged
      residues studied, 6 have not been previously investigated. The most dramatic
      effects of mutation were observed with beta H91, beta D392, and beta K424. beta
      H91E showed a pronounced shift of the pH optimum for both reduction of thio-NADP+
      by NADH (forward reaction) and reduction of 3-acetylpyridine-NAD+ by NADPH
      (reverse reaction) to lower pH. This mutant catalyzed a cyclic reduction of 3
      acetylpyridine-NAD+ by NADH in the presence of NADP(H) with a pH profile also
      shifted toward a lower pH. These results are consistent with a mechanism where
      the normal forward and reverse reactions are indeed limited by
      protonation/deprotonation of beta H91. The cyclic reaction was affected by
      mutations of beta H91, probably through conformational changes involving the
      active NADP(H) site. The beta D392A mutant was inactive with regard to forward
      and reverse reactions, but showed a wild-type-like pH dependence for the partly
      active cyclic reaction. However, Km,app for NADP(H) in this reaction was elevated
      50-100-fold, suggesting that beta D392 is located in or near the NADP(H)-binding
      site. Transhydrogenases contain a conserved beta K424-beta R425-beta S426
      sequence that has been proposed to be important for NADP(H) binding. beta K424R
      was strongly inhibited and showed an 18-fold increased Km,app for NADPH in the
      reverse reaction as compared to wild type. Consequently, this mutation affected
      all NADP(H)-linked activities and essentially abolished the unspecific
      interaction of NAD(H) with this site. The pH dependences of the forward and
      reverse reactions, as well as the cyclic reaction, were shifted to a lower pH as
      compared to the wild-type enzyme, and the salt dependence was also altered.

PMID- 9931034
TI  - Structure and dynamics of peptide-amphiphiles incorporating triple-helical
      proteinlike molecular architecture.
AB  - Organized polymeric assemblies that incorporate bioactive sequences and
      structures are finding important applications for the study of protein structure
      function relationships. We have recently described a heteropolymeric peptide
      amphiphile system that forms organized structures in solution and on surfaces.
      While the overall three-dimensional features of peptide-amphiphiles have been
      studied previously, the precise environment of specific residues, particularly
      those within biologically active regions, have not been examined in detail. In
      the present study, we have used heteronuclear single quantum coherence (HSQC) and
      inverse-detected 1H-15N NMR spectroscopy to examine the structure and dynamics of
      a peptide and peptide-amphiphile that incorporate the alpha1(IV)1263-1277 ([IV
      H1]) amino acid sequence from type IV collagen. Three variants of the sequence
      (Gly-Pro-Hyp)4-[IV-H1]-(Gly-Pro-Hyp)4 were constructed with a single 15N-labeled
      Gly placed in the middle of the N-terminal (Gly-Pro-Hyp)4 region (residue Gly7),
      in the middle of the [IV-H1] sequence (residue Gly19), or in the middle of the C
      terminal (Gly-Pro-Hyp)4 region (residue Gly34). These peptides were also N
      terminally acylated with hexanoic acid to create an analogous series of 15N
      labeled peptide-amphiphiles. HSQC spectra indicated that both the peptide and the
      peptide-amphiphile were in triple-helical conformation at low temperature,
      supporting prior circular dichroism (CD) spectroscopic results. The intensities
      of the triple-helical cross-peaks were stronger for the peptide-amphiphile,
      consistent with an enhanced triple-helical thermal stability within the peptide
      amphiphile construct compared to that of the peptide alone. Relative relaxation
      values for the peptide-amphiphile monomeric and trimeric species were consistent
      with those reported previously for other triple-helical peptides. Relaxation
      measurements indicated that the triple-helical [IV-H1] region did not appear to
      be dramatically more flexible than the Gly-Pro-Hyp regions. The angle between Gly
      N-H bonds and the helix dyad axis, determined from the relaxation data, was
      within the range expected for triple helices. Overall, the peptide headgroup of
      the C6-(Gly-Pro-Hyp)4-[IV-H1]-(Gly-Pro-Hyp)4 peptide-amphiphile appears to form a
      continuous triple helix that behaves similarly, in a dynamic sense, to a triple
      helical peptide. The enhanced thermal stability of the peptide-amphiphile
      compared to the analogous triple-helical peptide, along with the multitude of
      organized structures formed by lipidlike compounds, suggest that peptide
      amphiphiles could be utilized as targeted liposomes, sensors, receptors, or
      enzymes.

PMID- 9931036
TI  - Abnormal Testosterone:Epitestosterone ratios after dehydroepiandrosterone
      supplementation.

PMID- 9931037
TI  - Spectroscopic and clinical aspects of noninvasive glucose measurements.
AB  - Frequent determination of glucose concentrations in diabetic patients is an
      important tool for diabetes management. This requires repetitive lancing and
      finger bleeding. Use of noninvasive (NI) detection techniques offers several
      advantages, such as the absence of pain and exposure to sharp objects and
      biohazard materials, the potential for increased frequency of testing, and hence,
      tighter control of the glucose concentrations, and the potential for a closed
      loop system including a monitor and an insulin pump. These potential advantages
      have led to considerable interest in the commercialization of NI glucose
      monitoring devices. Review of the scientific, patent, and commercial literature
      indicates that the spectroscopic basis for NI determination of glucose is not yet
      well established, and attempts at commercialization may be several steps ahead of
      our understanding the origin and characteristics of an in vivo glucose-specific
      or glucose-related signal. Several technologies have potential for leading to
      viable measuring devices, but most of the data are based on in vitro
      experimentation. Because of the technical complexity of in vivo glucose
      measurements, this review aims at discussing the gap between the established need
      and current technology limitations.

PMID- 9931038
TI  - Efficiency of two different nine-loci short tandem repeat systems for DNA typing
      purposes.
AB  - BACKGROUND: Genotyping based on short tandem repeat (STR) regions is widely used
      in human identification and parentage testing, in gene mapping studies, and as an
      approach to studies on the etiopathogenesis and diagnosis of hereditary diseases.
      We wished to study a new analytical approach that uses capillary electrophoresis
      and multicolor fluorescence in place of slab gel electrophoresis. METHODS: We
      evaluated the efficiency for parentage and forensic purposes of the AmpFLSTR
      Profiler PlusTM typing kit that is used with the ABI Prism 310 Genetic Analyzer
      (System-2 STR), and that of a widely used panel of nine STRs analyzed with
      conventional slab-gel electrophoresis followed by radioactive detection (System-1
      STR). System-2 STR, based on automated capillary electrophoresis and automated
      sizing of the alleles by Genotyper 2.0 software, was used to determine the allele
      frequency of the nine loci in 157 Caucasian subjects from southern Italy. On the
      basis of the data obtained, we submitted 40 trios to parentage testing. RESULTS:
      A higher median probability of paternity attribution and power of exclusion were
      obtained with System-2 STR vs System-1 STR: respectively, 99.99% and 99.95% (P
      <0.05) for attribution; and five and four excluding loci (P <0.05) for exclusion.
      The most informative and highly discriminating loci were D18S51, D21S11, and FGA.
      The combined probability of matching-by-chance for all nine STRs was 1.36 x 10(
      12) for System-2 compared with 1.11 x 10(-7) obtained with the other system. The
      internal standard and allelic ladder of the System-2 STR facilitated accurate and
      precise genotyping; furthermore, System-2 STR and was faster than the
      conventional System-1 STR. CONCLUSIONS: The System-2 STR allows rapid testing
      with higher probabilities of attribution and a higher power of exclusion than
      with the comparison method with slab-gel electrophoresis.

PMID- 9931039
TI  - Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia.
AB  - BACKGROUND: There is much recent interest in the biologic and diagnostic
      implication of cell-free non-host DNA in the plasma and serum of human subjects.
      To determine if quantitative abnormalities of circulating non-host DNA may be
      associated with certain pathologic processes, we used circulating fetal DNA in
      preeclampsia as a model system. METHODS: We studied 20 preeclamptic women and 20
      control subjects of comparable gestational age (means, 32 and 33 weeks,
      respectively). Male fetal DNA in maternal serum was measured using real-time
      quantitative PCR for the SRY gene on the Y chromosome. RESULTS: The imprecision
      (CV) of the assay was 2.7%. The median circulating fetal DNA was increased
      fivefold in 20 preeclamptic women compared with 20 control pregnant women (381 vs
      76 genome-equivalents/mL, P <0.001). CONCLUSIONS: These observations suggest that
      preeclampsia is associated with disturbances in the liberation and/or clearance
      mechanisms of circulating DNA. These results also raise the possibility that
      measurement of circulating DNA may prove useful as a marker for the diagnosis
      and/or monitoring of preeclampsia.

PMID- 9931040
TI  - Cobalamin deficiency in general practice. Assessment of the diagnostic utility
      and cost-benefit analysis of methylmalonic acid determination in relation to
      current diagnostic strategies.
AB  - Diagnosing cobalamin deficiency is often difficult. We investigated the
      diagnostic strategies that 224 general practitioners used to assess cobalamin
      status and the criteria on which they based their decisions to supplement
      patients. From all serum cobalamin analyses carried out at a single laboratory
      during 1993, individuals with serum cobalamin concentrations <300 pmol/L were
      identified, and one patient per general practitioner was included. When serum
      methylmalonic acid (s-MMA) values >0.376 micromol/L were used as the "reference
      standard" for cobalamin deficiency, the serum cobalamin assay had a diagnostic
      sensitivity of 0.40 and a specificity of 0.98. With the same reference standard,
      the diagnostic accuracy of the physicians' decision to supplement patients had
      the same specificity but a higher sensitivity (0.51). Cost-benefit analysis
      indicated that measurement of s-MMA can be recommended in patients with serum
      cobalamin >60-90 pmol/L and <200-220 pmol/L, depending on its diagnostic
      accuracy.

PMID- 9931041
TI  - Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and
      cardiac troponin I by the triage cardiac panel for detection of myocardial
      infarction.
AB  - This multicenter study evaluated the Biosite Triage(R) Cardiac Panel as a
      quantitative, multimarker, whole blood system for the detection of acute
      myocardial infarction (MI). Optimum cutoffs for the discrimination of acute MI (n
      = 192 patients, 59 with MI) as determined by ROC curve analyses were as follows:
      0.4 microgram/L for cardiac troponin I (cTnI); 4.3 microgram/L for the creatine
      kinase MB isoenzyme (CK-MB); and 107 microgram/L for myoglobin. The Triage Panel
      showed the following concordances for detection or rule-out of MI compared with
      established devices: cTnI >89%; CK-MB >81%; myoglobin >69%. No significant
      differences were present between methods for the same marker. Diagnostic
      efficiencies demonstrated comparable sensitivities and specificities for the
      diagnosis of MI in patients presenting with symptoms compared with the Dade,
      Beckman, and Behring CK-MB, cTnI, and myoglobin assays; the ratio of sensitivity
      to specificity for each marker was as follows: cTnI, 98%:100%; CK-MB, 95%:91%;
      myoglobin, 81%:92%. The areas under the ROC curves for the Biosite myoglobin, CK
      MB, and cTnI were 0.818, 0.905, and 0.970, respectively; the areas were
      significantly different, P <0.05. In patients with skeletal muscle injury and
      renal disease, the Triage cTnI showed 94% and 100% specificity, respectively. The
      Triage panel offers clinicians a whole blood, point-of-care analysis of multiple
      cardiac markers that provides excellent clinical sensitivity and specificity for
      the detection of acute MI.

PMID- 9931043
TI  - Determination of cardiac troponin I forms in the blood of patients with acute
      myocardial infarction and patients receiving crystalloid or cold blood
      cardioplegia.
AB  - To determine the forms of cardiac troponin I (cTnI) circulating in the
      bloodstream of patients with acute myocardial infarction (AMI) and patients
      receiving a cardioplegia during heart surgery, we developed three immunoenzymatic
      sandwich assays. The first assay involves the combination of two monoclonal
      antibodies (mAbs) specific for human cTnI. The second assay involves the
      combination of a mAb specific for troponin C (TnC) and an anti-cTnI mAb. The
      third assay was a combination of a mAb specific for human cardiac troponin T
      (cTnT) and an anti-cTnI mAb. Fifteen serum samples from patients with AMI, 10
      serum samples from patients receiving crystalloid cardioplegia during heart
      surgery, and 10 serum samples from patients receiving cold blood cardioplegia
      during heart surgery were assayed by the three two-site immunoassays. We
      confirmed that cTnI circulates not only in free form but also complexed with the
      other troponin components (TnC and cTnT). We showed that the predominant form in
      blood is the cTnI-TnC binary complex (IC). Free cTnI, the cTnI-cTnT binary
      complex, and the cTnT-cTnI-TnC ternary complex were seldom present, and when
      present, were in small quantities compared with the binary complex IC. Similar
      results were obtained in both patient populations studied. These observations are
      essential for the development of new immunoassays with improved clinical
      sensitivity and for the selection of an appropriate cTnI primary calibrator.

PMID- 9931042
TI  - Multicenter clinical and analytical evaluation of the AxSYM troponin-I
      immunoassay to assist in the diagnosis of myocardial infarction.
AB  - We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the
      detection of acute myocardial infarction (AMI). At four sites, the total
      imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration
      was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM
      and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good
      correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI)
      - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39
      3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy
      individuals was </=0.5 microgram/L, whereas the ROC curve-determined cutoff for
      AMI was 2.0 microgram/L. This gave a diagnostic sensitivity of 91.8% and
      specificity of 92.4% when tested in serial samples collected within 24 h of
      admission in 633 patients presenting with chest pain, of which 122 had an AMI.
      The concordances of the AxSYM cTnI with the Stratus cTnI, OPUS cTnI, and Access
      cTnI were 95.3%, 95.1%, and 94.3%, respectively, from patients with suspected
      AMI. The AxSYM cTnI demonstrated excellent clinical specificity, >/=96%, in
      skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery
      patients.

PMID- 9931044
TI  - Dihydrofolate reductase enzyme inhibition assay for plasma methotrexate
      determination using a 96-well microplate reader.
AB  - Microplate reader assays offer several advantages over conventional
      spectrophotometric assays. We adapted the dihydrofolate reductase (DHFR) enzyme
      inhibition assay for use in a 96-well microplate reader to measure plasma
      methotrexate (MTX) concentrations. The assay is linear from 0.01 to 0.1
      micromol/L. The within-run CVs at 0.03 micromol/L and 0.08 micromol/L MTX were
      4.0% and 2.7%, respectively, and the interday (total) CVs were 7.6% and 1.8%.
      Cross-reactivity with the inactive MTX metabolite 2, 4-diamino-N10-methylpteroic
      acid (DAMPA) was 3.9%, significantly less than that described with commercial
      immunoassays; with 7-hydroxymethotrexate cross-reactivity was 1.7%. In addition
      to sensitivity and specificity, the advantages of this assay are small sample
      volumes, simultaneous analysis of multiple samples, and rapid turnaround. Because
      of its greater specificity, the DHFR enzyme inhibition assay may be useful when
      DAMPA is present in plasma samples and HPLC is not available.

PMID- 9931045
TI  - Tetrahydropalmatine poisoning: diagnoses of nine adult overdoses based on
      toxicology screens by HPLC with diode-array detection and gas chromatography-mass
      spectrometry.
AB  - BACKGROUND: Tetrahydropalmatine (THP) is a neuroactive alkaloid with analgesic
      and hypnotic action. Its analysis is important because cases of human poisonings
      have emerged as a result of unregulated use of some proprietary
      biopharmaceuticals containing purified THP. METHODS: We established analytical
      parameters for HPLC with diode-array detection (HPLC-DAD) and gas chromatography
      mass spectrometry (GC-MS) for the detection of THP in serum and urine. Nine
      acutely THP-poisoned adults were thus screened over 16 months. RESULTS: All
      patients recovered quickly after mild neurological disturbance. In general, THP
      was metabolized rapidly and excreted as polar metabolites in urine. Serum THP was
      measured in five cases and found to be <0.1-1.2 mg/L (<0.3-3.4 micromol/L).
      Paired analyses of urine with and without glucuronidase treatment clarified the
      disposition of THP. Our GC-MS method with trimethylsilane derivatization
      identified O-desmethyl metabolites. With a uniform solid-phase extraction, the
      HPLC-DAD procedure detected intact glucuronide metabolites. CONCLUSION: Intact
      glucuronide metabolites of THP are sensitive markers for THP exposures. Our
      methods and findings provide practical tools and information for surveillance of
      intoxication caused by excessive THP intake.

PMID- 9931046
TI  - Evaluation of a capillary electrophoresis method for routine determination of
      hemoglobins A2 and F.
AB  - Hemoglobin A2 (Hb A2) and hemoglobin F (Hb F) are important analytes in the
      diagnosis and follow up of Hb diseases. We evaluated a new capillary zone
      electrophoresis (CZE) kit for Hb A2 and Hb F measurements. The imprecision ranged
      from 3% to 6% for Hb A2 and Hb F at physiological and pathological
      concentrations. The method compared well with cation-exchange HPLC for Hb A2 and
      Hb F and with anion-exchange chromatography in microcolumns (MAEC), for Hb A2.
      Nevertheless, higher results were obtained [Hb A2 CZE (%) = 1.233 Hb A2 HPLC -
      0.2; Hb A2 CZE (%) = 1.190 Hb A2 MAEC + 0.1; Hb FCZE (%) = 1.118 Hb FHPLC + 0.4],
      and new reference values had to be determined (Hb A2 2.7-3.8%; Hb F <1.2%).
      Quantification of Hb A2 was not influenced by Hb S. Measurement of Hb F was
      accurate and precise except at low concentrations in Hb AS patients. This new CZE
      kit is rapid, precise, and reliable, and seems appropriate for use in clinical
      laboratories.

PMID- 9931047
TI  - One-step direct assay for mature-type adrenomedullin with monoclonal antibodies.
AB  - Adrenomedullin (AM) is a potent hypotensive peptide. Plasma contains mature-type
      AM (m-AM), which is amidated at the carboxy terminus, and an intermediate, AM
      Gly. We developed a one-step two-site IRMA specific for determining human m-AM
      with monoclonal antibodies. The detection limit was 0.5 pmol/L, and the working
      range (CV <15%) was 1-300 pmol/L. Dilution of plasma samples showed good
      linearity. The recovery of added AM was 91-118%. The intra- and interassay
      imprecision values (CVs) were 4.4-8.2% and 5.5-8.3%, respectively. The assay had
      no cross-reactivity with AM-Gly or other peptides similar to AM. The mean (+/-
      SD) plasma human m-AM concentration of 61 healthy subjects was 1.18 +/- 0.65
      pmol/L. In conclusion, our IRMA makes it possible to specifically measure m-AM,
      using a small amount of plasma sample (0.2 mL) by a one-step overnight assay
      without prior extraction. Our simplified method would be suitable for clinical
      studies on AM, especially when large numbers of samples must be processed.

PMID- 9931048
TI  - Influence of aromatase inhibitors on plasma total homocysteine in postmenopausal
      breast cancer patients.
AB  - In this study, we evaluated the effect of estrogen suppression with three
      aromatase inhibitors, aminoglutethimide (n = 30), formestane (n = 12), and
      exemestane (n = 10), and the progestin megestrol acetate (n = 21) on plasma total
      homocysteine (tHcy) in patients suffering from advanced breast cancer. Treatment
      with 1 g/day aminoglutethimide for 2 and 3-5 months increased plasma tHcy by a
      mean value of 24.5% [95% confidence interval, 10.5-40.4%] at 2 months and 35.8%
      (95% confidence interval, 18.2-55.9%) at 3-5 months, corresponding to increases
      in the mean plasma tHcy of 1.90 and 3.67 micromol/L, respectively. In contrast,
      none of the other treatment options influenced plasma tHcy concentrations. The
      finding that aminoglutethimide, but none of the other aromatase inhibitors or
      megestrol acetate, influenced plasma tHcy suggests that this effect is achieved
      by mechanisms not related to suppression of plasma estrogens or to the
      glucocorticoids administered in concert.

PMID- 9931049
TI  - Study of calcium metabolism in idiopathic hypercalciuria by strontium oral load
      test.
AB  - Calcium excretion and absorption were evaluated in hypercalciuric calcium stone
      formers by the study of Sr2+ excretion and absorption after an oral load. Ca2+
      stone formers (n = 140) were studied, and the results were compared in the 83 of
      them who had idiopathic hypercalciuria and in the 57 who had Ca2+ excretion
      within reference values. Hypercalciuric patients showed increased renal Sr2+
      clearance (CRE; 5.26 +/- 0.358 vs 3.29 +/- 0.277 mL/min; P <0.001), whereas Sr2+
      absorption [assessed as the area under the serum concentration-time curve (AUC)]
      was increased at 30 and 60 min (1.53 +/- 0.087 vs 1.21 +/- 0.071 mmol. L-1. min;
      P <0.05), but not at 240 min after the load. In hypercalciuric patients, the AUCs
      were positively correlated with urinary Sr2+ fractional excretion (P <0. 001).
      Conversely, in normocalciuric patients plasma parathyroid hormone (PTH) was
      negatively correlated with the AUCs (P <0.01) and CRE (P <0.05), whereas 1,25
      dihydroxyvitamin D plasma concentrations normalized to PTH were positively
      correlated with the AUCs (P <0.05). The results of Sr2+ load tests suggest that
      in the hypercalciuric population, Ca2+ absorption is altered predominantly in the
      duodenum and that the normal regulation exerted by calciotropic hormones on
      tubular and enteral Ca2+ handling is lost.

PMID- 9931050
TI  - Coupled-column liquid chromatographic analysis of catecholamines, serotonin, and
      metabolites in human urine.
AB  - A column-switching HPLC system was utilized for the simultaneous determination of
      epinephrine, norepinephrine, dopamine, serotonin, and their metabolites
      metanephrine, normetanephrine, 3, 4-dihydroxyphenylacetic acid, homovanillic
      acid, and 5-hydroxyindoleacetic acid in human urine. The sample was injected
      directly onto a C18-alkyl-diol silica precolumn, which separated the analytes
      from matrix. The analytes were eluted from the precolumn onto the analytical
      column by the use of column-switching techniques and were then separated on the
      analytical column by means of ion-pair reversed-phase HPLC. The analytes were
      then oxidized to the corresponding quinones and converted into fluorescent
      derivatives by reaction with meso-1,2-diphenylethylenediamine.

PMID- 9931052
TI  - Increased fecal porphyrins in acute intermittent porphyria.

PMID- 9931051
TI  - System to monitor a portion of the total testing process in medical clinics and
      laboratories: evaluation of a split-specimen design.
AB  - To evaluate a split-specimen design to identify problems in the testing process
      in hospital and physician office laboratories, we examined the testing for serum
      total cholesterol (n = 646) and potassium (n = 732) at 11 medical clinics
      evaluating 30-199 patients (mean, 125). Clinic personnel collected three tubes of
      blood from each patient. One specimen was processed routinely, the second was
      sent to a referral laboratory (RL), and the third specimen was sent to a holding
      facility for storage. The corresponding stored sample was retrieved and divided
      into three audit samples randomly and when result difference for the first two
      specimens exceeded critical values; one audit sample was sent to the original
      participant, the second to the RL, and the third to a referee laboratory. When
      three criteria were used, the result discrepancy rates were 2.5-8.7% for
      potassium and 1.5-4.6% for cholesterol. The split-specimen design could be
      implemented and evaluated as a monitoring system for a portion of the testing
      process.

PMID- 9931053
TI  - Prevention of the decrease in sensitivity of an amperometric glucose sensor in
      undiluted human serum 

PMID- 9931054
TI  - Capillary zone electrophoresis for the diagnosis of congenital
      hemoglobinopathies.

PMID- 9931055
TI  - Evaluation of glycated globins by matrix-assisted laser desorption/ionization
      mass spectrometry.

PMID- 9931056
TI  - Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a
      clinical laboratory setting.

PMID- 9931057
TI  - Lectin ELISA for the c-erb-B2 tumor marker protein p185 in patients with breast
      cancer and controls.

PMID- 9931058
TI  - Oral dehydroepiandrosterone supplementation can increase the
      testosterone/epitestosterone ratio.

PMID- 9931059
TI  - Highly sensitive and specific fluorescence reverse transcription-PCR assay for
      the pseudogene-free detection of beta-actin transcripts as quantitative
      reference.

PMID- 9931060
TI  - Arsenic speciation in human organs following fatal arsenic trioxide poisoning--a
      case report.
AB  - The aim of this investigation was to study the distribution of arsenic species in
      human organs following fatal acute intoxication by arsenic trioxide. The
      collected autopsy samples of most organs were ground and dried, and the total
      arsenic was measured by electrothermal atomic absorption spectrometry (ETAAS).
      The arsenic species--inorganic arsenic, in the form of arsenite [As(III)] and
      arsenate [As(V)], and its metabolites [monomethylarsonic acid (MMA) and
      dimethylarsinic acid (DMA)]--were quantified by ETAAS after extraction with
      methanol/water (1:1, by volume) and separation by HPLC. The results indicate that
      after acute intoxication, the liver and kidneys show the highest concentrations
      of total arsenic and that the total concentration in blood is 7- to 350-fold less
      concentrated than in organs. In all organs, As(III) is the predominant species,
      and MMA is more concentrated than DMA. MMA and DMA are more prevalent in lipidic
      organs (49% of total arsenic) compared with other organs (25% of total arsenic).
      As(V) was found in small quantities in the liver, kidneys, and blood.

PMID- 9931061
TI  - Rapid detection of a pentanucleotide deletion polymorphism in the human alpha2
      macroglobulin gene.

PMID- 9931062
TI  - Novel single nucleotide polymorphism (9678G-->A) for linkage analysis of acute
      intermittent porphyria.

PMID- 9931063
TI  - Reference values of serum IgA subclasses in caucasian adults by
      immunonephelometry.

PMID- 9931064
TI  - "Citation classics in clinical chemistry": contributions by AACC members duly
      noted.

PMID- 9931065
TI  - Thoughts on after the genome IV.

PMID- 9931066
TI  - False-positive hCG assay results leading to unnecessary surgery and chemotherapy
      and needless occurrences of diabetes and coma.

PMID- 9931067
TI  - Limitations of the paired t-test for evaluation of method comparison data.

PMID- 9931068
TI  - Interlaboratory variability for total homocysteine analysis in plasma.

PMID- 9931069
TI  - Urinary free cortisol is not affected by short-term water diuresis.

PMID- 9931071
TI  - Compiled by david E. Bruns, editor (dbruns@aacc.org) 

PMID- 9931072
TI  - Annual progress report: our 20th anniversary celebration.

PMID- 9931073
TI  - Story of the birth of the journal called Hypertension.

PMID- 9931074
TI  - Is gene therapy for hypertension possible?

PMID- 9931075
TI  - Role of the alpha2B-adrenergic receptor in the development of salt-induced
      hypertension.
AB  - Salt sensitivity is a common trait in patients with essential hypertension and
      seems to have both an inherited and an acquired component (eg, is influenced by
      aging and renal insufficiency). Experimental evidence suggests that salt loading
      induces hypertension via a neurogenic mechanism mediated by the alpha2-adrenergic
      receptors (alpha2-AR). To explore the alpha2-AR subtype involved in this
      mechanism, we studied 2 groups of mice genetically engineered to be deficient in
      one of the 3 alpha2-AR subtype genes (either alpha2B-AR +/- or alpha2C-AR -/-
      knockout mice) compared with their wild-type counterparts. The mice (n=10 to 14
      in each group) were submitted to subtotal nephrectomy and given 1% saline as
      drinking water for up to 35 days. Blood pressure (BP) was monitored by tail-cuff
      readings and confirmed at the end point by direct intra-arterial BP recording.
      The alpha2B-AR-deficient mice had an attenuated BP response in this protocol
      (baseline 101.8+/-2.7 versus end point 109.9+/-2.8 mm Hg), whereas the BP of
      their wild-type counterparts went from a baseline 101.9+/-2.3 to an end point
      141.4+/-7.1 mm Hg. The other 2 groups had BP increases of 44. 6+/-5.17 and 46.7+/
      7.01 mm Hg, with no difference between the mice deficient in the alpha2C-AR gene
      subtype versus their wild-type counterparts. Body weight, renal remnant weight,
      and residual renal function were no different among groups. These data suggest
      that a full complement of alpha2B-AR genes is necessary to raise BP in response
      to dietary salt loading, whereas complete absence of the alpha2C-AR subtype does
      not preclude salt-induced BP elevation. It is unclear whether the mechanism(s)
      involved in this process are of central origin (inability to increase sympathetic
      outflow), vascular origin (inability to vasoconstrict), or renal origin
      (inability to retain excess salt and fluid).

PMID- 9931076
TI  - Normotensive salt sensitivity: effects of race and dietary potassium.
AB  - -Normotensive salt sensitivity, a putative precursor of hypertension, might be
      quite frequent in African Americans (blacks) and less frequent in Caucasian
      Americans (whites), but only when dietary potassium is deficient and not when
      maintained well within the normal range. We tested this hypothesis in 41
      metabolically controlled studies of 38 healthy normotensive men (24 blacks, 14
      whites) who ate a basal diet low in sodium (15 mmol/d) and marginally deficient
      in potassium (30 mmol/d) for 6 weeks. Throughout the last 4 weeks, NaCl was
      loaded (250 mmol/d); throughout the last 3, potassium was supplemented (as
      potassium bicarbonate) to either mid- or high-normal levels, 70 and 120 mmol/d.
      Salt sensitivity, defined as an increase in mean arterial blood pressure >/=3 mm
      Hg with salt loading, was deemed "moderate" if increasing </=10 mm Hg and
      "severe" if increasing more. When dietary potassium was 30 mmol/d, salt loading
      induced a mean increase in blood pressure only in blacks (P<0.001), and salt
      sensitivity occurred in most blacks but not whites (79% vs 36% (P<0.02).
      Supplementing potassium only to 70 mmol/d attenuated moderate salt sensitivity
      similarly in blacks and whites; 120 mmol/d abolished it, attenuated severe salt
      sensitivity, which occurred in a quarter of affected blacks, and suppressed the
      frequency and severity of salt sensitivity in blacks to levels similar to those
      observed in whites. These observations demonstrate that in most normotensive
      black men but not white men, salt sensitivity occurs when dietary potassium is
      even marginally deficient but is dose-dependently suppressed when dietary
      potassium is increased within its normal range. Such suppression might prevent or
      delay the occurrence of hypertension, particularly in the many blacks, in whom
      dietary potassium is deficient.

PMID- 9931077
TI  - Safety of nifedipine in angina pectoris: a meta-analysis.
AB  - -Our objective was to compare cardiovascular event rates in patients with stable
      angina receiving nifedipine as monotherapy or combination therapy and in active
      drug controls. A MEDLARS search of published articles from 1966 to 1995 in
      English, French, German, Italian, or Spanish, supplemented by a manual search of
      bibliographies, identified 60 randomized controlled trials that met protocol
      criteria. Blinded articles were extracted by 2 physicians. The pooled risks of
      death, withdrawal, and cardiovascular event were computed and expressed as odds
      ratios (ORs) for all nifedipine formulations and relative to same study control
      drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine
      exposures (1.14%) and 19 events in 2655 other active drug exposures (0.72%).
      Unadjusted ORs for nifedipine versus controls were 1.40 (95% CI, 0.56 to 3.49)
      for major events (death, nonfatal myocardial infarction, stroke,
      revascularization procedure), 1.75 (95% CI, 0.83 to 3.67) for increased angina,
      and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased
      angina). Episodes of increased angina were more frequent on immediate-release
      nifedipine (OR, 4.19 [95% CI, 1.41 to 12.49]) and on nifedipine monotherapy (OR,
      2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was
      significantly higher than that for sustained-release/extended-release nifedipine
      (P=0.001), and the OR for nifedipine monotherapy was higher than that for
      nifedipine combination therapy (P=0.03). Increased risks of cardiovascular events
      in patients with stable angina on nifedipine were due primarily to more episodes
      of increased angina, confined to the immediate-release formulation and to
      nifedipine monotherapy.

PMID- 9931078
TI  - Sympathoinhibitory effects of central nifedipine in spontaneously hypertensive
      rats on high versus regular sodium intake.
AB  - -The putative central sympathoinhibitory actions of the dihydropyridine calcium
      antagonist nifedipine and the effect of dietary sodium on these actions were
      investigated in spontaneously hypertensive rats (SHR). Regular or high dietary
      salt was administered from 4 to 8 weeks of age. At 8 weeks, blood pressure (BP),
      heart rate (HR), and renal sympathetic nerve activity were recorded in conscious
      rats at rest as well as in response to intravenous (50 microg/kg) and
      intracerebroventricular (5 and 50 microg/kg) injections of nifedipine and
      intracerebroventricular injections of vehicle. Resting mean arterial pressure was
      higher in SHR on high versus regular salt (159+/-3 versus 135+/-4 mm Hg; P<0.
      05). Nifedipine administered intracerebroventricularly decreased BP as well as
      renal sympathetic nerve activity and HR in a dose-related manner. The responses
      reached their peak at 3 to 5 minutes and lasted approximately 30 minutes. Peak
      decreases in BP, renal sympathetic nerve activity, and HR in response to both
      doses of nifedipine were significantly larger in SHR on high versus regular salt.
      Nifedipine administered intravenously also decreased BP but, in contrast, caused
      (reflex) increases in renal sympathetic nerve activity and HR. On both diets,
      intracerebroventricular vehicle did not affect mean arterial pressure, renal
      sympathetic nerve activity, or HR. These data indicate that in contrast to its
      peripheral vasodilator effect, centrally administered nifedipine may decrease
      sympathetic outflow and therefore BP and HR. The enhanced sympathoinhibitory and
      depressor responses to nifedipine in SHR on high versus regular salt suggest that
      the sympathetic hyperactivity induced by high salt intake is dependent on
      neuronal calcium influx via L-type channels.

PMID- 9931079
TI  - A test of the "epinephrine hypothesis" in humans.
AB  - -According to the "epinephrine hypothesis," circulating epinephrine taken up by
      sympathetic nerves is coreleased with norepinephrine during sympathetic
      stimulation and binding of coreleased epinephrine to presynaptic beta
      adrenoceptors augments exocytotic release of norepinephrine, contributing to high
      blood pressure. This study examined whether infusion of a physiologically active
      amount of epinephrine affects subsequent vascular responses and the estimated
      rate of entry of norepinephrine into regional venous plasma (norepinephrine
      spillover). Each of 3 experiments included intravenous infusion of 3H
      norepinephrine, measurements of forearm vascular resistance, and intra-arterial
      infusion of epinephrine (3 ng/min per deciliter forearm volume). In experiment 1,
      subjects underwent lower body negative pressure (LBNP-25 mm Hg) before and after
      intra-arterial epinephrine; in experiment 2, LBNP and intra-arterial yohimbine
      before and after intra-arterial epinephrine; and in experiment 3, intravenous
      nitroprusside before and after intra-arterial epinephrine. In all subjects, intra
      arterial epinephrine produced ipsilateral pallor and decreased forearm vascular
      resistance. Ipsilateral venous epinephrine increased by 10-fold. Epinephrine did
      not affect forearm vasoconstrictor responses to LBNP or vasodilator responses to
      intra-arterial yohimbine or intravenous nitroprusside; did not affect venous
      norepinephrine levels or norepinephrine spillover during LBNP, yohimbine, LBNP
      during yohimbine, or nitroprusside; and did not increase venous epinephrine
      levels during any of these manipulations. Loading of forearm sympathetic
      terminals with epinephrine therefore does not augment subsequent neurogenic
      vasoconstriction or norepinephrine release in the human forearm in response to
      sympathetic stimulation. The findings are inconsistent with the epinephrine
      hypothesis.

PMID- 9931080
TI  - Influence of heart rate on mortality in a French population: role of age, gender,
      and blood pressure.
AB  - -The aim of the present study was to assess the effects of high heart rate on
      mortality in different subgroups in a French population according to age, gender,
      and blood pressure levels. We studied 19 386 subjects (12 123 men, 7263 women),
      aged 40 to 69 years, who had a routine health examination at the Centre
      d'Investigations Preventives et Cliniques (IPC) between 1974 and 1977. Heart rate
      (HR) measured by ECG was classified into 4 groups: HR1, <60; HR2, 60 to 80; HR3,
      81 to 100; and HR4, >100 bpm. Mortality data were recorded for the period of 1974
      through 1994. In both sexes, HR was a significant predictor of noncardiovascular
      mortality. In men, the relative risk (95% confidence interval) for cardiovascular
      death after adjustment for age and other risk factors in the HR2, HR3, and HR4
      groups was 1.35 (1.01 to 1.80), 1.44 (1.04 to 2.00), and 2.18 (1.37 to 3.47),
      respectively, when compared with HR1. In women, HR did not influence
      cardiovascular mortality. The association of HR with cardiovascular mortality in
      men was (1) related to a strong association with coronary but not cerebrovascular
      mortality, (2) independent of age and hypertension, and (3) influenced by the
      level of pulse pressure; in patients with high pulse pressure (>65 mm Hg),
      accelerated HR was not associated with increased cardiovascular mortality. In
      conclusion, in a large French population, accelerated resting HR represents an
      independent predictor of noncardiovascular mortality in both genders, and of
      cardiovascular mortality in men, independent of age and the presence of
      hypertension. Further investigations are needed to explain the complex
      interactions between HR, pulse pressure, and cardiovascular complications.

PMID- 9931081
TI  - Autoantibodies to OxLDL are decreased in individuals with borderline
      hypertension.
AB  - -Elevated antibody levels to oxidized low-density lipoprotein (aOxLDL) have been
      shown to correlate with the degree of atherosclerosis in some studies. On the
      other hand, immunization of experimental animals with OxLDL, leading to enhanced
      aOxLDL levels, inhibits the development of the disease. The role of antibodies to
      OxLDL during different stages of disease development is thus not clear. The
      objective of this study was to determine the level of aOxLDL in early
      cardiovascular disease, such as borderline hypertension (BHT). Seventy-three men
      with BHT were matched with 75 age-matched normotensive (NT) men (diastolic blood
      pressures, 85 to 94 and <80 mm Hg, respectively). Antibody levels to epitopes of
      OxLDL were determined by use of conventional and chemiluminescence ELISA
      techniques. Presence of carotid atherosclerosis was determined by B-mode
      ultrasonography; atherosclerotic plaques were detected in 29 individuals. BHT men
      had significantly lower aOxLDL levels of IgG class (P=0.001) and IgM class
      (P=0.001) than NT controls, as determined using chemiluminescence ELISA. Similar
      results were obtained using conventional ELISA, with which aOxLDL of IgG (P=0.
      0002) and IgM (P=0.026) classes and antibody levels to malondialdehyde-LDL were
      significantly lower in BHT individuals. There was no difference in antibody
      levels between individuals with or without carotid atherosclerosis. It is not
      clear whether the decreased aOxLDL levels in BHT are due to a decreased immune
      reaction to OxLDL or to an increased consumption of aOxLDL due to binding to
      early atherosclerotic lesions. The possible implications of these findings are
      discussed.

PMID- 9931082
TI  - Direct effects of colchicine on myocardial function: studies in hypertrophied and
      failing spontaneously hypertensive rats.
AB  - -The aging spontaneously hypertensive rat (SHR) is a model in which the
      transition from chronic stable left ventricular hypertrophy to overt heart
      failure can be observed. Although the mechanisms for impaired function in
      hypertrophied and failing cardiac muscle from the SHR have been studied, none
      accounts fully for the myocardial contractile abnormalities. The cardiac
      cytoskeleton has been implicated as a possible cause for myocardial dysfunction.
      If an increase in microtubules contributes to dysfunction, then myocardial
      microtubule disruption by colchicine should promote an improvement in cardiac
      performance. We studied the active and passive properties of isolated left
      ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart
      failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and
      age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were
      analyzed before and up to 90 minutes after the addition of colchicine (10(-5),
      10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed
      by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F
      groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26;
      SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in
      SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness
      constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F
      P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30
      minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any
      group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90
      minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study
      fail to demonstrate improvement of intrinsic muscle function in SHR with heart
      failure after colchicine. Thus, in the SHR there is no evidence that colchicine
      induced cardiac microtubular depolymerization affects the active or passive
      properties of hypertrophied or failing left ventricular myocardium.

PMID- 9931083
TI  - Ultrasonic myocardial texture versus Doppler analysis in hypertensive heart: a
      preliminary study.
AB  - -Doppler-derived parameters of transmitral flow are useful indices of diastolic
      dysfunction in the hypertensive heart. Different degrees of myocardial
      involvement in hypertensive heart can be detected by videodensitometric
      myocardial textural analysis. The aim of this study was to compare Doppler
      derived and ultrasonic videodensitometric parameters in the differentiation of
      healthy hearts from hypertensive hearts. We compared a group of age-matched (59+/
      9 years) male essential hypertensive patients (n=53) with normotensive healthy
      subjects as controls (n=32). All subjects provided ambulatory blood pressure
      measurements for the evaluation of 24-hour mean systolic and diastolic blood
      pressure. A transmitral flow Doppler analysis was performed on all subjects. A
      quantitative analysis of the echocardiographic digitized imaging was performed
      with the help of a calibrated digitization system to calculate the septum and the
      posterior wall textural parameters. The myocardial mean gray level (MGL) was
      calculated to derive the cyclic variation index (CVI): (MGLend-diastolic-MGLend
      systolic)/MGLend-diastolic x100. When compared with controls, the hypertensive
      patients showed a significantly lower CVI for both septum (-11.1+/-26.8% versus
      34. 7+/-16.3%; P<0.001) and posterior wall (-11.2+/-27.6% versus 38. 2+/-15.4%;
      P<0.001). Individual analyses for the ratio of peak transmitral flow velocity in
      early diastole to the peak transmitral flow velocity in late diastole showed that
      only 24% of the patients (13/53) were discriminated from normal subjects by this
      parameter. Individual analyses for CVI, however, at both septum and posterior
      wall levels, showed that 74% of the patients (39/53) were discriminated from
      normal subjects by this second parameter. In comparison with Doppler-derived
      indices of diastolic filling, the videodensitometric parameters showed a
      significantly higher ability to discriminate between hypertensive subjects and
      normal controls.

PMID- 9931084
TI  - Hypertension and arsenic exposure in Bangladesh.
AB  - -A prevalence comparison of hypertension among subjects with and those without
      arsenic exposure through drinking water was conducted in Bangladesh to confirm or
      refute an earlier observation of a relation in this respect. Wells with and
      without present arsenic contamination were identified, and we interviewed and
      examined 1595 subjects who were depending on drinking water from these wells for
      living, all >/=30 years of age. The interview was based on a questionnaire, and
      arsenic exposure was estimated from the history of well-water consumption and
      current arsenic levels. Of the 1595 subjects studied, 1481 had a history of
      arsenic-contaminated drinking water, whereas 114 had not. Time-weighted mean
      arsenic levels (in milligrams per liter) and milligram-years per liter of arsenic
      exposure were estimated for each subject. Exposure categories were assessed as
      <0.5 mg/L, 0.5 to 1.0 mg/L, and >1.0 mg/L and alternatively as <1.0 mg-y/L, 1.0
      to 5.0 mg-y/L, >5.0 but </=10.0 mg-y/L, and >10.0 mg-y/L, respectively.
      Hypertension was defined as a systolic blood pressure of >/=140 mm Hg in
      combination with a diastolic blood pressure of >/=90 mm Hg. Corresponding to the
      exposure categories, and using "unexposed" as the reference, the prevalence
      ratios for hypertension adjusted for age, sex, and body mass index were 1.2, 2.2,
      2.5 and 0.8, 1.5, 2.2, 3.0, in relation to arsenic exposure in milligrams per
      liter and milligram-years per liter, respectively. The indicated dose-response
      relationships were significant (P<<0.001) for both series of risk estimates.
      These results suggest that arsenic exposure may induce hypertension in humans.

PMID- 9931085
TI  - Binge drinking and ambulatory blood pressure.
AB  - -The effect of alcohol drinking in raising blood pressure (BP) is rapidly
      reversible. However, there is only limited information on the effect of binge
      drinking on BP values. In this study, 20 healthy men who were all social drinkers
      drank alcohol (2.2 g/kg) in controlled circumstances on a Saturday evening.
      Ambulatory BP measurement (ABPM) values were compared with ABPM values of the
      same subjects during the previous sober Saturday, separately throughout 6 hours
      of intoxication, throughout 6 hours when blood alcohol levels decreased, and
      throughout 6 hangover hours. During the intoxication period, both mean systolic
      BP and mean diastolic BP were 5 mm Hg higher (P=0.0183 and P=0.0529,
      respectively) and the pulse was 18 beats per minute faster (P=0.0001) compared
      with the corresponding sober period during the previous weekend. While blood
      alcohol levels decreased after drinking, mean systolic BP was 4 mm Hg lower (P=0.
      0331), diastolic BP was 5 mm Hg lower (P=0.0058), and pulse was 15 bpm faster
      (P=0.0001) than during the sober weekend. No statistically significant difference
      was found between the weekends in BP values during the hangover period. Drinking
      seems to increase both systolic and diastolic BP during intoxication but not
      during hangover. During the period when blood alcohol levels are decreasing,
      usually at night, both pressure levels fall to less than the basic level. These
      major and rapid changes in BP values might increase the likelihood of strokes,
      which are seen in increased numbers among young adults, especially during
      weekends and holidays.

PMID- 9931086
TI  - Evidence for peroxynitrite formation in the vasculature of women with
      preeclampsia.
AB  - -Preeclampsia is a multisystemic disorder of pregnancy in which the normal
      vascular adaptations to pregnancy are compromised. Oxidative stress as well as
      endothelial cell dysfunction have been implicated as pathophysiological features
      of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO).
      However, NO is also known to react with superoxide anions (produced under
      conditions of oxidative stress), yielding peroxynitrite that may impair vascular
      function. Our objective was to use immunohistochemical techniques to determine
      whether there is evidence of peroxynitrite formation in the maternal systemic
      vasculature of women with preeclampsia. Vessels were obtained from a biopsy of
      subcutaneous fat at the time of cesarean section from normal pregnant (n=7) and
      preeclamptic (n=7) women or at the time of hysterectomy from nonpregnant women
      (n=5). There were significantly more vessels staining with greater intensity for
      nitrotyrosine and endothelial NO synthase in the endothelium of vessels from
      women with preeclampsia compared with that of normal pregnant women or
      nonpregnant women. Both endothelial and smooth muscle cells from all vessels
      showed evidence for the presence of superoxide dismutase (SOD), an enzyme that
      scavenges superoxide anions. However, the intensity of staining for SOD in the
      endothelium was significantly lower in the preeclamptic and nonpregnant women
      than in normal pregnant women. These data of increased endothelial NO synthase,
      decreased SOD, and increased nitrotyrosine immunostaining in the maternal
      vasculature of women with preeclampsia suggest increased peroxynitrite formation.
      We speculate that peroxynitrite is involved in endothelial cell dysfunction in
      preeclamptic women and contributes to the pathophysiology of this pregnancy
      disorder.

PMID- 9931087
TI  - Renal characteristics and effect of angiotensin suppression in oral contraceptive
      users.
AB  - -The determinants of the increase in arterial blood pressure associated with the
      use of estrogen-progestogen oral contraceptives (OC) remain poorly known. The
      purpose of this study was to assess the renal characteristics and the role of the
      renin-angiotensin system in women with OC-associated hypertension. Urinary
      clearances of technetium-labeled diethylene triaminopentaacetic acid (glomerular
      filtration rate) and 131I-ortho iodohippurate (effective renal plasma flow) were
      estimated before and after acute administration of captopril in 38 women who
      became hypertensive while taking OC, 38 non-OC users with essential hypertension
      matched for age, body mass index, and level of blood pressure, and 38
      normotensive women (19 with and 19 without OC). Plasma renin activity was higher
      in OC hypertensives when compared with those with essential hypertension, but
      captopril-induced changes in blood pressure and renal hemodynamics and function
      were similar in both groups. In addition, 24-hours urinary albumin excretion was
      increased in OC users when compared with nonusers with similar arterial blood
      pressure. In 13 hypertensive women followed up for 6 months after OC withdrawal,
      a decrease in plasma renin activity, blood pressure, and glomerular filtration
      rate but no significant change in urinary albumin excretion and captopril-induced
      changes in blood pressure and renal hemodynamics were observed. These results
      indicate that the use of OC is associated with an increased albuminuria and no
      evidence of a prominent role for the renin-angiotensin system in the maintenance
      of high blood pressure and renal hemodynamics when compared with non-OC users
      with essential hypertension.

PMID- 9931088
TI  - Differential regulation of renal angiotensin subtype AT1A and AT2 receptor
      protein in rats with angiotensin-dependent hypertension.
AB  - -This study was designed to investigate distribution and regulation of the renal
      AT1A and AT2 subtype receptors in rats with either systemic angiotensin II (Ang
      II)-induced hypertension or acute phase renal hypertension (2-kidney, 1-clip
      [2K1C] or 2-kidney, 1-figure-of-8-wrap [2K1W]). In normal rat kidneys, positive
      immunostaining for the AT1A receptor was observed in the intrarenal vasculature,
      glomeruli, proximal and distal tubules, and collecting ducts. The AT2 receptor
      was localized mainly to the glomeruli. The AT1A but not AT2 receptor protein
      expression was significantly reduced in rats with 10-day systemic Ang II-induced
      hypertension. In both 7-day 2K1C and 3-day 2K1W rats, the AT1A receptor was
      significantly reduced in ischemic and contralateral kidneys compared with sham
      operated control rats. Reduction in AT2 receptor expression was observed only in
      the ischemic kidneys in 2K1C and 2K1W renal hypertensive rats. These results
      demonstrate that the AT1A receptor is widely distributed in the glomerulus and
      all other nephron segments of the rat kidney. Renal AT1A but not AT2 receptor
      protein is downregulated in rats with Ang II-induced hypertension. In renal
      hypertensive rats, the AT1A receptor is bilaterally downregulated and the AT2
      receptor is downregulated only in the ischemic kidney.

PMID- 9931089
TI  - Proximal tubular angiotensin II levels and renal functional responses to AT1
      receptor blockade in nonclipped kidneys of Goldblatt hypertensive rats.
AB  - -Previous studies have shown that whereas the nonclipped kidney in two-kidney,
      one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA,
      intrarenal angiotensin II (Ang II) levels are not suppressed; however, the
      distribution and functional consequences of intrarenal Ang II remain unclear. The
      present study was performed to assess the plasma, kidney, and proximal tubular
      fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in
      the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in
      proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels
      averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g.
      Thus, as found in kidneys from normal rats with normal renin levels, proximal
      tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the
      confounding effects of decreases in mean arterial pressure (MAP), we administered
      the nonsurmountable AT1 receptor antagonist candesartan directly into the renal
      artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not
      significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but
      effectively prevented the renal vasoconstriction elicited by an intra-arterial
      bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular
      filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal
      blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater
      increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min
      1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C
      hypertensive rats. These results show that proximal tubular fluid concentrations
      of Ang II are in the nanomolar range and are much higher than can be explained on
      the basis of plasma levels. Further, the data show that the intratubular levels
      of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in
      kidneys with normal renin content and could be exerting effects to suppress renal
      hemodynamic and glomerular function and to enhance tubular reabsorption rate.

PMID- 9931090
TI  - Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene.
AB  - -Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive
      hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism
      at -20 located between the TATA box and transcriptional initiation site. We show
      here that when nucleoside A is present at -20, this sequence binds to the
      estrogen receptor. We also show that transcriptional activity of reporter
      constructs containing human angiotensinogen gene promoter with nucleoside A at 
      20 is increased on cotransfection of an expression vector containing human
      estrogen receptor-alpha coding sequence in human hepatoma cells (HepG2) followed
      by estrogen treatment. On the other hand, adenoviral major late transcription
      factor binds preferentially to this region of the promoter when nucleoside C is
      present at -20. We also show that reporter constructs containing human
      angiotensinogen gene promoter with nucleoside C at -20 have increased basal
      promoter activity on transient transfection in HepG2 cells as compared with
      reporter constructs with nucleoside A at -20. Our data suggest that C/A
      polymorphism at -20 may modulate the expression of human angiotensinogen gene in
      a sex-specific manner.

PMID- 9931091
TI  - Increased expression of matrix metalloproteinase-2 in the thickened intima of
      aged rats.
AB  - -To characterize remodeling of elastic arteries with aging and to investigate its
      potential mechanisms, matrix metalloproteinase-2 (MMP-2), intracellular adhesive
      molecule-1 (ICAM-1), transforming growth factor-beta (TGF-beta), and fibronectin
      protein levels were measured in the aortas of young adult (6 months) and aged (30
      months) Fischer 344XBN rats. At 30 versus 6 months, the thickness of the intima
      was 5-fold greater and contained marked increases in TGF-beta and ICAM-1, and
      fibronectin expression was enhanced throughout the aortic wall. Total MMP-2
      protein (Western blot) of 30-month-old rats was increased 8-fold over that of 6
      month-old rats (0.166+/-0.032 versus 0.020+/-0.006; P<0.01), and staining and
      activity were regionally localized to the intima, often near breaks in the
      internal elastic membrane and lamellae. Early passage, explanted smooth muscle
      cells (SMC) from aged aorta secreted more MMP-2 than those from young aorta;
      while basal MMP-2 production did not differ with age, after stimulation with
      cytokines (interleukin-1, tumor necrosis factor-alpha, or TGF-beta, 10 ng/mL each
      for 24 hours), MMP-2 production in SMC from 30-month-old rats increased to levels
      greater than those in 6-month-old rats. Thus, enhanced expression of TGF-beta,
      MMP-2, and ICAM-1 in the thickened vascular intima of aged rats may in part be
      produced by exaggerated SMC responses to cytokines and may have potential roles
      in intimal remodeling with aging.

PMID- 9931092
TI  - C-type natriuretic peptide attenuates evoked dopamine efflux by influencing
      Goalpha.
AB  - -Natriuretic peptides suppress adrenergic neurotransmission by a mechanism
      sensitive to pertussis toxin, suggesting that GTP-binding proteins are involved
      in the response. The major GTP-binding proteins present in the pheochromocytoma
      (PC12) cells used in this report are Goalpha and Gialpha2. We tested the
      hypothesis that the more abundant GTP-binding protein, Goalpha, mediates
      natriuretic peptide effects in PC12 cells by selectively ablating Goalpha from
      the cells with antisense oligodeoxynucleotides. The results indicate that a
      selective ablation of Goalpha with this technique eliminated C-type natriuretic
      peptide (CNP) effects and suppressed dopamine efflux evoked by a depolarizing
      stimulus. However, the activation of guanylyl cyclase (GC) by CNP was sustained
      after the Goalpha ablation. Further, Nomega-nitro-L-arginine methyl ester
      suppressed evoked dopamine efflux equally in the presence and absence of Goalpha.
      These results suggest that CNP attenuates evoked catecholamine efflux from PC12
      cells by a mechanism requiring Goalpha but independent of GC activation.

PMID- 9931093
TI  - Mechanisms of FK 506-induced hypertension in the rat.
AB  - -Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical
      utility of FK 506 is complicated by substantial hypertension and nephrotoxicity.
      To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic
      effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA
      of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide
      synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type
      natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the
      specific endothelin type A receptor antagonist FR 139317 on FK 506-induced
      hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks,
      elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the
      synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and
      230%, respectively). Little change was observed in the expression of ECE-1 mRNA
      and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the
      aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1.
      d-1) prevented FK 506-induced hypertension in rats. These results indicate that
      FK 506 may increase blood pressure not only by increasing ET-1 production but
      also by decreasing NO synthesis in the vasculature.

PMID- 9931095
TI  - Inotropic effects of endothelin-1: interaction with molsidomine and with BQ 610.
AB  - -In vivo studies could not detect a positive inotropy of endothelin (ET)-1 as
      described in in vitro experiments. ET-induced direct positive inotropy, which
      seems to be mediated by ETB receptors, may be antagonized in vivo by an indirect
      cardiodepressive effect owing to an ET-induced coronary vasoconstriction via ETA
      receptors. This study compares the effects of a dose of 1 nmol/kg ET-1 alone on
      myocardial contractility and myocardial energy metabolism with the effects of 1
      nmol/kg ET-1 after pretreatment with 5 mg/kg molsidomine or with 100 microg/kg of
      the ETA receptor antagonist BQ 610. We investigated the effects of ET-1 versus
      saline controls in open-chest rats. In addition to measurements in the intact
      circulation, myocardial function was examined by isovolumic registrations
      independent of peripheral vascular effects. We also studied the effect of ET-1 on
      myocardial high-energy phosphates. Pretreatment with molsidomine and BQ 610
      attenuated the ET-induced reduction of cardiac output (ET-1: -62%; molsidomine+ET
      1: -47%; BQ 610+ET-1: -27% different from controls). After a transient initial
      vasodilation, ET-1 raised total peripheral resistance (ET-1: +190%;
      molsidomine+ET-1: +171%; BQ 610+ET-1: +89%). BQ 610 was more effective in
      preventing ET-induced vasoconstriction. The increase of isovolumic peak first
      derivative of left ventricular pressure (ET-1: -2%; molsidomine+ET-1: +16%; BQ
      610+ET-1: +19%) after pretreatment with molsidomine or BQ 610 indicates that
      these drugs unmask the positive inotropy of ET-1. ET-induced myocardial ischemia
      was abolished by molsidomine and BQ 610. Pretreatment with molsidomine or
      blockade of ETA receptors by BQ 610 can unmask the positive inotropy of ET-1 by
      preventing ET-induced myocardial ischemia. The positive inotropic effect of ET-1
      seems to be mediated by ETB receptors.

PMID- 9931096
TI  - Structural autoregulation of terminal vascular beds: vascular adaptation and
      development of hypertension.
AB  - -It is widely accepted that the early phase of primary hypertension is
      characterized by elevated cardiac output, whereas in later stages the increased
      blood pressure is due to increased peripheral resistance. To study long-term
      effects of increased blood flow on peripheral resistance, structural adaptation
      of microvascular networks in response to changes in blood flow was simulated
      using a previously developed theoretical model. The diameter of each vessel
      segment was assumed to change in response to local levels of shear stress,
      transmural pressure, a metabolic stimulus dependent on blood flow rate, and a
      conducted stimulus. Network morphologies and topologies were derived from
      intravital microscopy of the rat mesentery. Adaptive responses to the 4 stimuli
      were quantitatively balanced to yield stable and realistic distributions of
      vascular diameters and blood flow rates when the total flow rate was set to
      observed levels. To simulate effects of increased cardiac output, network flow
      resistance after structural adaptation was determined for a range of flow rates.
      Resistance increased with increasing flow, and increases in pressure were up to 3
      fold greater than proportional to the increases in flow. According to the model,
      flow-dependent changes of network resistance result mainly from the vascular
      response to transmural pressure, which also causes arteriovenous asymmetry of
      diameters and pressure drops. Therefore, in vascular beds that exhibit
      arteriovenous asymmetry, increased flow may trigger increased flow resistance by
      a mechanism involving the tendency of vascular segments to reduce their luminal
      diameters in response to increased transmural pressure.

PMID- 9931094
TI  - Early-onset but not late-onset endothelin-A-receptor blockade can modulate
      hypertension, cerebral edema, and proteinuria in stroke-prone hypertensive rats.
AB  - -The ability of endothelin receptor blockade to prevent and to treat established
      cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously
      hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist
      A127722. SHRSP were subjected to 1% NaCl intake. The start of treatment with
      A127722 (35 and 70 mg. kg-1. d-1, respectively) was either synchronized with salt
      loading or initiated after the first observation of cerebral edema with T2
      weighted magnetic resonance imaging. In untreated control animals median survival
      was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset
      A127722 treatment increased median survival to 233 days (range, 92 to 407 days;
      P<0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days;
      P<0.05 versus control) with 70 mg/kg. The development of cerebral edema was
      prevented, and systolic blood pressure and proteinuria were dose-dependently
      reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages
      in the basal ganglia shortly before death. Late-onset A127722 treatment failed to
      affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral
      edema was reduced but not as well as in early-onset treatment. Development of
      hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722
      treatment was initiated at the start of salt-loading. However, A127722 treatment
      did not prolong survival in SHRSP with cerebral edema. This suggests that in
      SHRSP the endothelin A receptor participates actively in the development of
      increased blood pressure and initiation of organ damage but participates
      minimally in established malignant hypertension and progression of target-organ
      damage.

PMID- 9931099
TI  - Proceedings of the council for high blood pressure research, 1998 

PMID- 9931098
TI  - The hypertension primer project : An educational experiment 

PMID- 9931097
TI  - Interferon regulatory factors regulate interleukin-1beta-converting enzyme
      expression and apoptosis in vascular smooth muscle cells.
AB  - -Apoptosis has been reported to play a pivotal role in vascular remodeling.
      However, cellular mechanisms of apoptosis in vascular smooth muscle cells (VSMCs)
      have not been well defined. In this study, we focused on interleukin-1beta
      converting enzyme (ICE), a key protease in the induction of apoptosis in
      lymphocytes and fibroblasts. We observed an increase in ICE mRNA expression in
      rat aortic VSMCs after serum depletion, with a peak at 12 hours and then a
      gradual decline. This was associated with DNA fragmentation, a hallmark of
      apoptosis and morphological changes of apoptosis. Treatment of these VSMCs with
      the ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic
      acid (YVAD-CHO) attenuated DNA fragmentation. The increased ICE mRNA expression
      was preceded by an increase in the mRNA expression of interferon regulatory
      factor (IRF)-1, peaking at 6 hours after serum removal, and a rapid but transient
      decrease in IRF-2 mRNA expression, reaching a nadir at 3 hours after serum
      depletion. To demonstrate that these reciprocal changes in IRF-1 and IRF-2
      regulated ICE expression and induced apoptosis, we transfected antisense
      oligonucleotides for IRF-1 and IRF-2 into VSMCs and examined ICE mRNA expression
      and apoptotic changes. IRF-1 antisense pretreatment attenuated the increase in
      ICE expression and reduced apoptotic changes, whereas IRF-2 antisense treatment
      increased ICE mRNA expression and enhanced apoptotic changes. Taken together, our
      results suggest that serum growth factor depletion in VSMCs upregulates IRF-1 and
      downregulates IRF-2, thereby increasing ICE expression and inducing apoptosis.

PMID- 9931100
TI  - Arthur C. Corcoran Memorial Lecture. Hormones and vasoprotection.
AB  - There is a strong link between menopause and increased cardiovascular disease
      incidence in women, and observational studies suggest that postmenopausal hormone
      replacement therapy reduces cardiovascular disease risk by about half.
      Observational studies suffer from important limitations, however, and the only
      published prospective controlled trial of the effects of hormone replacement
      therapy on cardiovascular outcomes, the Heart Estrogen-Progestin Replacement
      Study (HERS), showed no net benefit of continuous estrogen plus synthetic
      progestin treatment in women with established coronary disease. Fundamental
      mechanistic studies of the cellular and molecular events by which hormones
      protect (or fail to protect) blood vessels from damage are needed to define the
      role of postmenopausal hormone replacement therapy in cardiovascular disease
      prevention. Most studies suggest that estrogen inhibits the neointimal response
      to acute injury in normal blood vessels, but this vasoprotective effect was not
      seen in vessels with preexisting atherosclerosis. Studies from our laboratory in
      the rat carotid injury model have shown that estrogen inhibits neointima
      formation via effects on all 3 layers of the vascular wall, including inhibition
      of medial smooth muscle cell migration and proliferation, stimulation of regrowth
      of endothelium, and inhibition of adventitial cell migration into neointima. Our
      laboratory is currently using transduced (lacZ) syngeneic fibroblasts as
      'reporter' cells to delineate the factors that stimulate migration of adventitial
      cells into neointima after vascular injury and their modulation by estrogen and
      the other sex hormones. These fundamental studies will establish more rational
      strategies for therapeutic intervention in vascular diseases, including the basis
      for future gene therapy.

PMID- 9931101
TI  - Phytoestrogens inhibit growth and MAP kinase activity in human aortic smooth
      muscle cells.
AB  - -Estrogens are known to induce cardioprotective effects by inhibiting smooth
      muscle cell (SMC) growth and neointima formation. However, the use of estrogens
      as cardioprotective agents is limited by carcinogenic effects in women and
      feminizing effects in men. If noncarcinogenic and nonfeminizing estrogenlike
      compounds, such as natural phytoestrogens, afford cardioprotection, this would
      provide a safe method for prevention of cardiovascular disease in both men and
      women. Therefore, we evaluated and compared in human aortic SMCs the effects of
      phytoestrogens (formononetin, genistein, biochanin A, daidzein, and equol) on
      2.5% fetal calf serum-induced proliferation (3H-thymidine incorporation and cell
      number), collagen synthesis (3H-proline incorporation), and total protein
      synthesis (3H-leucine incorporation) and on PDGF-BB (25 ng/mL)-induced migration
      (modified Boydens chambers). Moreover, the effects of phytoestrogens on PDGF-BB
      (25 ng/mL)-induced mitogen-activated protein kinase (MAP kinase) activity in SMCs
      was also studied. Phytoestrogens inhibited proliferation, collagen and total
      protein synthesis, migration, and MAP kinase activity in a concentration
      dependent manner and in the following order of potency: biochanin
      A>genistein>equol>daidzein>formononetin. In conclusion, our studies provide the
      first evidence that in human aortic SMCs phytoestrogens inhibit mitogen-induced
      proliferation, migration and extracellular matrix synthesis and
      inhibit/downregulate MAP kinase activity. Thus, phytoestrogens may confer
      protective effects on the cardiovascular system by inhibiting vascular remodeling
      and neointima formation and may be clinically useful as a safer substitute for
      feminizing estrogens in preventing cardiovascular disease in both women and men.

PMID- 9931102
TI  - TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent.
AB  - -Migration of vascular smooth muscle cells (VSMC) is a key event in neointimal
      formation and atherosclerosis that may be linked to the accumulation of
      inflammatory cells and release of chemotactic cytokines. Tumor necrosis factor
      alpha (TNF-alpha) induces chemotaxis of inflammatory cells and fibroblasts, but
      little is known about chemotactic signaling by TNF-alpha in VSMC. The aim of this
      study was to investigate the role of TNF-alpha in VSMC migration and to elucidate
      the chemotactic signaling pathways mediating this action. TNF-alpha (50 to 400
      U/mL) induced migration of cultured rat aortic VSMC in a dose-dependent manner.
      Because activation of the extracellular signal-regulated kinase 1/2 mitogen
      activated protein kinase (MAPK) is known to be required in platelet-derived
      growth factor-directed and angiotensin II-directed migration of these cells, we
      used the MAPK-inhibitor PD98059 to determine if chemotactic signaling by TNF
      alpha involves the MAPK pathway as well. We found that TNF-alpha-directed
      migration was substantially inhibited by PD98059. TNF-alpha (100 U/mL)
      transiently activated MAPK with a maximal induction 10 minutes after stimulation
      that returned to baseline levels by 2 hours after treatment. Only a single peak
      of increased MAPK activity was seen. PD98059 also blocked TNF-alpha-stimulated
      MAPK activation in a concentration-dependent manner, which is consistent with its
      inhibition of TNF-alpha-directed migration. To identify which TNF-alpha receptor
      is involved in TNF-alpha-induced MAPK activation, antibodies against the p55 TNF
      alpha receptor-1 (TNF-R1) and the p75 TNF-alpha receptor-2 (TNF-R2) were used.
      VSMC express both receptors, but TNF-alpha-induced MAPK activation was inhibited
      only by the TNF-R1 antibody. The TNF-R2 antibody had no effect.
      Thiazolidinediones are known to inhibit TNF-alpha signaling in adipose tissue and
      attenuate platelet-derived growth factor-directed and angiotensin II-directed
      migration in VSMC. We therefore investigated the effects of the
      thiazolidinediones troglitazone (TRO) and rosiglitazone (RSG) on TNF-alpha
      induced migration. Both TRO and RSG inhibited migration, but neither attenuated
      TNF-alpha-induced MAPK activation, indicating that their antimigration activity
      was exerted downstream of MAPK. These experiments provide the first evidence that
      early activation of MAPK is a crucial event in TNF-alpha-mediated signal
      transduction leading to VSMC migration. Moreover, inhibition of TNF-alpha
      directed migration by the insulin sensitizers TRO and RSG underscores their
      potential as vasculoprotective agents.

PMID- 9931103
TI  - Adenosine inhibits collagen and total protein synthesis in vascular smooth muscle
      cells.
AB  - -The objective of this study was to characterize the effects of exogenous, drug
      induced and cAMP-adenosine pathway-derived adenosine on collagen synthesis by and
      hypertrophy of vascular smooth muscle cells (SMCs). Confluent vascular SMCs were
      stimulated with 2.5% fetal calf serum in the presence and absence of adenosine
      receptor agonists [adenosine, 2-chloroadenosine, N6-cyclopentyladenosine, 5'-N
      ethylcarboxamidoadenosine, 5'-N-methylcarboxamidoadenosine, and 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxamino adenosine], drugs that increase
      levels of endogenous adenosine [erythro-9-(2-hydroxy-3-nonyl) adenine,
      dipyridamole, and iodotubericidin], and cAMP (increases adenosine by conversion
      to AMP and hence to adenosine via the cAMP-adenosine pathway). Adenosine receptor
      agonists inhibited fetal calf serum-induced collagen and total protein synthesis
      (as assessed by [3H]proline and [3H]leucine incorporation, respectively) with a
      relative potency profile consistent with the effects being mediated by adenosine
      A2B receptors. Erythro-9-(2-hydroxy-3-nonyl) adenine, dipyridamole,
      iodotubericidin, and cAMP also inhibited collagen and total protein synthesis.
      The effects of 2-chloroadenosine, erythro-9-(2-hydroxy-3-nonyl) adenine,
      iodotubericidin, and cAMP on collagen and total protein synthesis were attenuated
      by KF17837 and 1,3-dipropyl-8-p-sulfophenylxanthine (selective and nonselective
      A2 receptor antagonists, respectively) but not by 8-cyclopentyl-1, 3
      dipropylxanthine (selective A1 receptor antagonist). These studies indicate that
      exogenous, drug-induced and cAMP-adenosine pathway-derived adenosine inhibit
      vascular SMC collagen synthesis and hypertrophy via A2B receptors. Thus,
      exogenous A2B receptor agonists and drugs that modulate endogenous adenosine
      levels may protect against vasoocclusive disorders by attenuating extracellular
      matrix synthesis by and cellular hypertrophy of vascular SMCs. Moreover, the cAMP
      adenosine pathway may protect against vascular hypertrophy.

PMID- 9931104
TI  - Purinoceptor-mediated calcium signaling in preglomerular smooth muscle cells.
AB  - -The current studies were performed to determine the contribution of calcium
      mobilization and voltage-dependent calcium influx to the increase in [Ca2+]i
      elicited by ATP and UTP. Suspensions of freshly isolated smooth muscle cells were
      prepared from preglomerular microvessels by enzymatic digestion and loaded with
      the Ca2+-sensitive dye fura 2. The effect of ATP and UTP on [Ca2+]i was studied
      on single cells with standard microscope-based fluorescence photometry
      techniques. Resting [Ca2+]i averaged 80+/-3 nmol/L (n=219 single cells from 58
      dispersions). ATP (100 micromol/L) increased [Ca2+]i to a peak value of 845+/-55
      nmol/L (n=70 single cells from 38 dispersions) before stabilizing at 124+/-81
      nmol/L. Similarly, 100 micromol/L UTP (n=39 single cells from 26 dispersions)
      stimulated a peak increase in [Ca2+]i of 1426+/-584 nmol/L before reaching a
      stable plateau of 123+/-10 nmol/L. The [Ca2+]i response to ATP and UTP was also
      assessed in the absence of extracellular calcium. In these studies, exposure to
      100 micromol/L ATP induced a transient peak increase in [Ca2+]i, with the plateau
      phase being totally abolished. In contrast, exposure to 100 micromol/L UTP under
      calcium-free conditions resulted in no detectable change in the UTP-mediated
      increase in [Ca2+]i. The role of L-type calcium channels in the response was
      assessed with the calcium channel antagonist diltiazem. Incubation with diltiazem
      (10 micromol/L) markedly reduced the response to ATP, whereas the response to UTP
      was only slightly reduced. These data demonstrate that both ATP and UTP directly
      stimulate a biphasic increase in [Ca2+]i in renal microvascular smooth muscle
      cells. Furthermore, the data suggest that the elevation of [Ca2+]i elicited by
      ATP is largely dependent on calcium influx through L-type calcium channels,
      whereas the response to UTP appears to derive primarily from mobilization of
      calcium from intracellular stores.

PMID- 9931105
TI  - Involvement of PYK2 in angiotensin II signaling of vascular smooth muscle cells.
AB  - -PYK2, a recently identified Ca2+-sensitive tyrosine kinase, has been implicated
      in extracellular signal-regulated kinase (ERK) activation via several G protein
      coupled receptors. We have reported that angiotensin II (Ang II) induces Ca2+
      dependent transactivation of the epidermal growth factor receptor (EGFR) which
      serves as a scaffold for preactivated c-Src and downstream adaptors (Shc/Grb2),
      leading to ERK activation in cultured rat vascular smooth muscle cells (VSMC).
      Herein we demonstrate the involvement of PYK2 in this cascade. Ang II rapidly
      induced tyrosine phosphorylation of PYK2, whose effect was completely inhibited
      by an AT1 receptor antagonist and an intracellular Ca2+ chelator. A Ca2+
      ionophore also induced PYK2 tyrosine phosphorylation to a level comparable with
      that by Ang II, whereas phorbol ester-induced phosphorylation was less than that
      by Ang II. Moreover, PYK2 formed a complex coprecipitable with catalytically
      active c-Src after Ang II stimulation. Although a selective EGFR kinase inhibitor
      completely abolished Ang II-induced recruitment of Grb2 to EGFR and markedly
      attenuated Ang II-induced ERK activation, it had no effect on Ang II-induced PYK2
      tyrosine phosphorylation or its association with c-Src and Grb2. These data
      suggest that the AT1 receptor uses Ca2+-dependent PYK2 to activate c-Src, thereby
      leading to EGFR transactivation, which preponderantly recruits Grb2 in rat VSMC.

PMID- 9931106
TI  - Angiotensin-(1-7) reduces smooth muscle growth after vascular injury.
AB  - Regulation of vascular smooth muscle cell growth is critical to the maintenance
      of normal blood flow and vessel patency. Angiotensin-(1-7) [Ang-(1-7)] inhibits
      proliferation of vascular smooth muscle cells in vitro and opposes the mitogenic
      effects of angiotensin II. The present study investigated whether Ang-(1-7)
      inhibits vascular smooth muscle cell growth in vivo by determining its effect on
      neointimal formation and medial remodeling in balloon-injured carotid arteries.
      The carotid arteries of adult male Sprague-Dawley rats were injured with a
      balloon embolectomy catheter. Ang-(1-7) in saline (24 microg/kg per hour) or
      saline alone was infused intravenously for 12 days after injury. Pumps containing
      bromodeoxyuridine were implanted at the same time to determine DNA synthesis.
      Intravenous infusion increased plasma Ang-(1-7) to 166. 0+/-41.2 fmol/mL (n=6)
      compared with 46.9+/-4.2 fmol/mL (n=8) in saline-infused rats. Plasma
      concentrations of Ang II were not changed by Ang-(1-7) infusion. Elevation in
      circulating Ang-(1-7) had no effect on either blood pressure or heart rate
      compared with saline controls. Histomorphometric analysis of carotid arteries
      indicated that Ang-(1-7) infusion significantly reduced neointimal area compared
      with rats infused with saline (0.063+/-0.011 versus 0. 100+/-0.009 mm2; P<0.05).
      In contrast, Ang-(1-7) infusion had no effect on medial area of the injured or
      the contralateral uninjured artery compared with saline controls. Ang-(1-7)
      infusion also reduced the rate of DNA synthesis in both the neointima and the
      media of the injured vessels. Therefore, exogenous Ang-(1-7) inhibited vascular
      smooth muscle cell proliferation associated with balloon-catheter injury. Similar
      increases in endogenous plasma Ang-(1-7) and inhibition of neointimal growth were
      observed in rats after angiotensin-converting enzyme inhibitor or angiotensin
      type 1 receptor antagonist administration, suggesting that Ang-(1-7) may
      contribute to the in vivo antiproliferative effects of these agents on vascular
      smooth muscle.

PMID- 9931107
TI  - Hypertension-induced end-organ damage : A new transgenic approach to an old
      problem.
AB  - Angiotensin (Ang) II-induced organ damage has fascinated students of hypertension
      since the work of Wilson and Byrom. We are investigating a double transgenic rat
      (dTGR) model, in which rats transgenic for the human angiotensinogen and renin
      genes are crossed. These rats develop moderately severe hypertension but die of
      end-organ cardiac and renal damage by week 7. The heart shows necrosis and
      fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome
      vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early
      on the endothelium, while the corresponding ligands are found on circulating
      leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1,
      and VEGF expression. The expression of TGF-beta and deposition of extracellular
      matrix proteins follows, which is accompanied by fibrinoid vasculitis in small
      vessels of the heart and kidneys. Angiotensin-converting enzyme inhibitors and
      AT1 receptor blockers each lowered blood pressure and shifted pressure
      natriuresis partially leftward by different mechanisms. When combined, they
      normalized blood pressure, pressure natriuresis, and protected from vasculopathy
      completely. Renin inhibition lowered blood pressure partially, but protected from
      vasculopathy completely. Endothelin receptor blockade had no influence on blood
      pressure but protected from vasculopathy and improved survival. We show evidence
      that Ang II stimulates oxidative stress directly or indirectly via endothelin 1
      and that NFkappaB is upregulated in this model. We speculate that the
      transcription factors NFkappaB and AP-1 are involved with initiating chemokine
      and cytokine expression, leading to the above cascade. The unique model and our
      pharmacological probes will enable us to test these hypotheses.

PMID- 9931108
TI  - Atrial natriuretic peptide gene delivery reduces stroke-induced mortality rate in
      Dahl salt-sensitive rats.
AB  - Atrial natriuretic peptide (ANP) is a powerful hormone with hypotensive,
      natriuretic, diuretic, and many other beneficial effects. Direct infusion of ANP
      in therapeutics has limited success because of its short half-life in the
      circulation. Our previous studies have shown that ANP gene delivery attenuates
      hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive (Dahl
      SS) rats. To investigate the potential therapeutic value of ANP gene delivery on
      salt-induced stroke and cerebrovascular disorders, an adenovirus harboring the
      human ANP gene (Ad.RSV-cANP) was injected into Dahl-SS rats on a high salt diet.
      A single intravenous injection of the ANP gene caused a significant reduction of
      blood pressure that lasted for more than 3 weeks. A maximal blood pressure
      reduction of 28 mm Hg was observed 2 weeks after gene delivery as compared with
      that of control rats injected with adenovirus harboring the LacZ gene under the
      control of the Rous sarcoma virus promoter (Ad.RSV-LacZ). Immunoreactive human
      ANP can be detected in the heart, lung, kidney, and brain of rats after gene
      delivery. The stroke mortality rate of Dahl-SS rats was significantly decreased
      (from 54% to 17% at 3 weeks and from 70% to 50% at 4 weeks after ANP gene
      delivery as compared with rats injected with control virus). ANP gene delivery
      also significantly attenuates salt-induced aortic hypertrophy as evidenced by
      reduced thickness of the aortic wall. This is the first study to demonstrate the
      potential of ANP gene delivery in reducing the mortality rate caused by
      cerebrovascular disorders and stroke. Successful application of this technology
      may have potential value in treating individuals with a high risk of stroke.

PMID- 9931109
TI  - Enalapril prevents tubulointerstitial lesions by hyperoxaluria.
AB  - Hyperoxaluria is a recognized cause of tubulointerstitial lesions, and this could
      contribute to development of hypertension and chronic renal failure. Enalapril
      has been effective against the progression of tubulointerstitial lesions in
      various animal models. The aim of the present study was to evaluate the
      usefulness of enalapril on the tubulointerstitial damage produced by oxalates.
      Two-month-old male Sprague-Dawley rats were separated into 4 groups, control with
      tap water (G1), hyperoxaluric (G2), hyperoxaluric+enalapril (G3), enalapril (G4),
      for 4 weeks. G2 and G3 rats were given 1% ethyleneglycol (ETG, precursor for
      oxalates), and G3 and G4 rats were given enalapril 20 mg/L in drinking water. At
      the end of the study, we evaluated renal tubulointerstitial lesions by a
      semiquantitative score. Urine albumin excretion, serum and urine nitric oxide
      production, tubulointerstitial immunostaining by alpha-smooth muscle actin,
      transforming growth factor-beta1, and collagen type III were measured. Rats
      belonging to the hyperoxaluric group treated with enalapril (G3) showed fewer
      tubulointerstitial lesions (1.3+/-0.2 versus 3+/-0.2; P<0.01), lower urine
      albumin excretion (8+/-2 mg/d versus 25+/-2 mg/d; P<0.01), less percentage of
      alpha-smooth muscle actin in renal interstitium (2+/-0.4% versus 13.5+/-2.4%;
      P<0.01), less percentage of transforming growth factor-beta1 in
      tubulointerstitial area (3.3+/-1% versus 13.3+/-2. 1%; P<0.01), less percentage
      of collagen type III interstitial deposition (0.7+/-0.5% versus 7+/-2.6%;
      P<0.01), and increased NO production in serum as well as urine (both P<0.01),
      when compared with the hyperoxaluric group not treated with enalapril (G2).
      Considering these data, we believe that enalapril, by several mechanisms of
      action, could provide an important benefit in the prevention of inflammatory
      response, transforming growth factor-beta1 tubulointerstitial production,
      collagen type III interstitial deposition, and finally, the progressive
      tubulointerstitial fibrosis caused by oxalates.

PMID- 9931110
TI  - Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution
      and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and
      vascular lesions characteristic of thrombotic microangiopathy seen in malignant
      nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid
      receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic
      lesions in these animals. This observation, together with our previous findings
      that angiotensin-converting enzyme inhibitors prevent the development of vascular
      damage, suggests that mineralocorticoids, as part of the renin-angiotensin
      aldosterone system, play a pathophysiological role in this model. In the present
      study, we examined whether chronic (2-week) infusion of aldosterone can reverse
      the renal vascular protective effects of captopril in SHRSP. SHRSP received
      vehicle (n=8); captopril alone (50 mg. kg-1. d-1, orally) (n=10); aldosterone
      infusion alone (40 microg. kg-1. d-1, SC) (n=7); or captopril and aldosterone at
      20 (n=6) or 40 (n=7) microg. kg-1. d-1. Systolic blood pressure was markedly
      elevated in all groups. Vehicle- and aldosterone-infused SHRSP developed severe
      proteinuria and comparable degrees of renal injury (21+/-3% and 29+/-3%,
      respectively) manifested as thrombotic and proliferative lesions in the
      arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels
      concomitant with marked reductions in proteinuria and the absence of histologic
      lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40
      microg. kg-1. d-1 in captopril-treated SHRSP resulted in the development of
      severe renal lesions (16+/-3% and 21+/-2%, respectively) and proteinuria
      comparable with that observed in SHRSP given either aldosterone or vehicle alone.
      These findings support a major role for aldosterone in the development of
      malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of
      blood pressure.

PMID- 9931111
TI  - Genomics and hypertension: concepts, potentials, and opportunities.
AB  - We are at the beginning of a biological revolution, spurred on by the Human
      Genome Project and associated studies. Within the next few years, expressed
      sequence tags (ESTs) representing all sequences expressed in humans will be
      determined and their genomic positions will be defined (STSs). The discovery of
      all the variants in the human genome that contribute to the genetic diversity of
      the human population will result in the construction of dense polymorphic maps.
      The rapid growth of the EST, STS, and single-nucleotide polymorphism (SNP)
      databases, coupled with impressive technological advances, will surely have a
      dramatic effect on biomedical research. In this review, we will examine the
      recent advances in genetics and genomics and place these within the context of
      medical research and patient care, with an emphasis on studies in the
      cardiovascular system.

PMID- 9931112
TI  - Telemetry for cardiovascular monitoring in a pharmacological study: new
      approaches to data analysis.
AB  - Radio-telemetry systems offer the ability to measure blood pressure and heart
      rate in experimental models of hypertension without the stress artifacts induced
      by some other methods. We therefore aimed to develop improved, nonparametric
      regression methods for radio-telemetry data and to use these to assess the
      effects of pharmacological interventions on cardiac and vascular hypertrophy in
      the stroke-prone spontaneously hypertensive rat. One control group and 5 groups
      treated either with losartan (alone or in combination with NG-nitro-L-arginine
      methyl ester [ L-NAME]), perindopril (also alone or in combination with L-NAME),
      or hydralazine plus hydrochlorothiazide were monitored for 4 weeks. Cardiac
      hypertrophy was assessed by the left ventricle plus septum weight to body weight
      ratio and vascular hypertrophy by flow-cytometry analysis of vascular smooth
      muscle cell polyploidy. Hemodynamic series were split into trend and cyclic
      components by the seasonal and trend decomposition procedure based on Loess and
      compared between groups by Loess regression modeling. Systolic and diastolic
      blood pressures were reduced systematically by losartan and perindopril (P<10(
      10)) but to a lesser extent by hydralazine plus hydrochlorothiazide (P<10(-8)),
      and diurnal variation was reduced in the latter group (P<10(-6)). L-NAME
      significantly reduced the hypotensive effect only of losartan. Vascular and
      cardiac hypertrophy were significantly attenuated with losartan or perindopril,
      but were unchanged with other treatments. The new analysis proposed here
      identifies differential effects on trends and cyclic variation and associations
      with regression of end-organ damage for losartan and perindopril compared with
      hydralazine plus hydrochlorothiazide. The method offers a powerful tool for
      detailed investigation of radio-telemetry data.

PMID- 9931114
TI  - Role of chromosome X in the Sabra rat model of salt-sensitive hypertension.
AB  - We carried out a total genome screen in the Sabra rat model of hypertension to
      detect salt-susceptibility genes. We previously reported in male animals the
      presence of 2 major quantitative trait loci (QTLs) on chromosome 1 that together
      accounted for most of the difference in the blood pressure (BP) response to salt
      loading between Sabra hypertension-prone rats (SBH/y) and Sabra hypertension
      resistant rats (SBN/y). In females, we reported on 2 major QTLs on chromosomes 1
      and 17 that together accounted for only two thirds of the difference in the BP
      response between the strains. On the basis of phenotypic patterns of inheritance
      in reciprocal F2 crosses, we proposed a role of the X chromosome. We therefore
      continued the search for the missing QTL in females that would account for the
      remaining difference in the BP response between the 2 strains using newly
      developed microsatellite markers and focusing on chromosome X. We screened an F2
      cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X
      microsatellite markers. We analyzed the averages of BP by genotype using ANOVA
      and the individual data using MAPMAKER/QTL. In female F2 progeny, we identified a
      segment on chromosome X that spans over 33.4 cM and shows significant
      cosegregation (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and
      DXMgh10) with systolic BP after salt loading. This segment has 2 apparent peaks
      at DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint linkage
      analysis with a free model detected 3 peaks (logarithm of the odds ratio [LOD]
      score >4.3) within the same chromosomal segment: One between DXMgh9 and DXMit4
      (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRat8 (LOD 5.2; 7.2%
      of variance), and a third between DXRat2 and DXRat4 (LOD 5.8; 7.5% of variance).
      On the basis of these findings and until congenic strains become available, our
      working assumption is that within chromosome X, 1 to 3 genetic loci contribute
      importantly to the BP response of female Sabra rats to salt. In male F2 progeny,
      we detected no significant cosegregation of any region on chromosome X with the
      BP response to salt loading. We conclude that in the female rat, salt
      susceptibility is mediated by 3 to 5 gene loci on chromosomes 1, 17, and X,
      whereas in the male rat, the X chromosome does not affect the BP response to
      salt.

PMID- 9931113
TI  - Effect of chromosome 19 transfer on blood pressure in the spontaneously
      hypertensive rat.
AB  - Linkage studies in the spontaneously hypertensive rat (SHR) have suggested that a
      gene or genes regulating blood pressure may exist on rat chromosome 19 in the
      vicinity of the angiotensinogen gene. To test this hypothesis, we measured blood
      pressure in SHR progenitor and congenic strains that are genetically identical
      except for a segment of chromosome 19 containing the angiotensinogen gene
      transferred from the normotensive Brown Norway (BN) strain. Transfer of this
      segment of chromosome 19 from the BN strain onto the genetic background of the
      SHR induced significant decreases in systolic and diastolic blood pressures in
      the recipient SHR chromosome 19 congenic strain. To test for differences in
      angiotensinogen gene expression between the congenic and progenitor strains, we
      measured angiotensinogen mRNA levels in a variety of tissues, including aorta,
      brain, kidney, and liver. We found no differences between the progenitor and
      congenic strains in the angiotensinogen coding sequence or in angiotensinogen
      expression that would account for the blood pressure differences between the
      strains. In addition, no significant differences in plasma levels of
      angiotensinogen or plasma renin activity were detected between the 2 strains.
      Thus, transfer of a segment of chromosome 19 containing angiotensinogen from the
      BN rat into the SHR induces a decrease in blood pressure without inducing any
      major changes in plasma angiotensinogen levels or plasma renin activity. These
      results indicate that the differential chromosome segment trapped in the SHR
      chromosome 19 congenic strain contains a quantitative trait locus that influences
      blood pressure in the SHR but that this blood pressure effect is not explained by
      differences in plasma angiotensinogen levels or angiotensinogen expression.

PMID- 9931115
TI  - Genetic polymorphism of CYP11B2 gene and hypertension in Japanese.
AB  - Low-renin hypertension is characterized by a high ratio of aldosterone to plasma
      renin activity (ALD/PRA), which may suggest inappropriately increased aldosterone
      biosynthesis. The genes for the enzymes involved in aldosterone synthesis may
      contribute to low-renin hypertension. We investigated the associations between
      genetic variations of CYP11B2 (aldosterone synthase) T(-344)C and hypertension in
      482 Japanese subjects. Subjects older than 50 years with a blood pressure <140/85
      mm Hg were considered normotensive (n=227 subjects), and subjects younger than 65
      years old with a BP >160/95 mm Hg were considered hypertensive (n=255 subjects).
      The frequency of the TC+CC genotypes in the normotensive group was significantly
      lower than in the hypertensive group. Logistic analysis on 482 subjects revealed
      that body mass index, gender, and the genotype of CYP11B2 T(-344)C were
      significantly associated with hypertension. ALD and PRA were assessed in 97
      subjects with hypertension, and the TC+CC genotypes were significantly associated
      with higher ALD/PRA. Sixty-five subjects with hypertension were assessed by 24
      hour ambulatory blood pressure monitoring, and the frequency of nondippers (a
      difference in mean blood pressure of <10% between the daytime [6 AM to 9 PM] and
      nighttime [9 PM to 6 AM] hours) was significantly higher in subjects with the
      TC+CC (hetero+homo mutation) genotype than in subjects with the TT (wild-type)
      genotype. Echocardiographic assessment (n=136) revealed that the ratio of left
      ventricular end-diastolic dimension to height tended to be higher in subjects
      with the TC+CC genotype than in subjects with the TT genotype. The present study
      suggests that the (-344)C allele of the CYP11B2 gene may be a genetic marker for
      low-renin hypertension in Japanese.

PMID- 9931116
TI  - TGF-beta1 DNA polymorphisms, protein levels, and blood pressure.
AB  - Transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine with
      fibrogenic properties, has been implicated in the pathogenesis of the vascular
      and target organ complications of hypertension. TGF-beta1 may also regulate blood
      pressure via stimulation of endothelin-1 and/or renin secretion. Herein we
      explored the hypothesis that circulating levels of TGF-beta1 protein (quantified
      using a TGF-beta1-specific sandwich ELISA) are correlates of blood pressure
      levels. This hypothesis was tested in 98 stable end-stage renal disease (ESRD)
      patients. (The use of ESRD patients as the study cohort eliminates renal function
      dependent alterations in circulating levels of TGF-beta1 protein.) In addition,
      in view of the previously reported correlation among TGF-beta1 DNA polymorphisms
      and systolic blood pressure, TGF-beta1 codon 25 genotype and alleles were
      identified in 71 hypertensive subjects and 57 normotensives using amplification
      refractory mutation system polymerase chain reaction. Our studies demonstrate for
      the first time that TGF-beta1 levels (209+/-13 ng/mL, mean+/-SEM) are positive
      correlates (Pearson correlation analysis) of mean arterial pressure (P=0.008),
      systolic pressure (P=0.02), and diastolic pressure (P=0. 01). We also report that
      a higher percentage of hypertensives (92%) compared with normotensives (86%) are
      homozygous for the arginine allele at codon 25. Our observations support the idea
      that genetically determined TGF-beta1 protein concentrations may play a role in
      blood pressure regulation in humans.

PMID- 9931117
TI  - Interleukin-1beta regulation of inducible nitric oxide synthase and
      cyclooxygenase-2 involves the p42/44 and p38 MAPK signaling pathways in cardiac
      myocytes.
AB  - The genes encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2, also known as prostaglandin-endoperoxide synthase-2) are induced in many
      types of cells in response to proinflammatory cytokines. We have previously shown
      that interleukin-1beta (IL) stimulates iNOS and COX-2 mRNA in cardiac myocytes.
      Because IL has been shown to activate mitogen-activated protein kinase (MAPK)
      signaling pathways in many different cells, we tested whether the p42/44 and p38
      MAPK pathways were involved in IL stimulation of iNOS and COX-2, using a specific
      inhibitor of p42/44 activation, PD98059 (PD), and the p38 inhibitor SB205380
      (SB). Nitrites were measured using the Griess reagent, prostaglandin PGE2 by an
      enzyme immunoassay, iNOS and COX-2 protein by Western blot analysis, and iNOS
      mRNA by Northern blot analysis. Tested separately, the p38 kinase and MAPK
      inhibitors partially reduced IL stimulation of nitrite, iNOS protein, and iNOS
      mRNA; used together, they completely abolished the effect of IL. SB and PD
      inhibited IL-stimulated COX-2 protein by 60% and 80%, respectively, and IL
      stimulated COX-2 protein was totally prevented by the combination of inhibitors.
      PGE2 production was inhibited more than 99% by either drug alone, suggesting a
      posttranslational effect on enzyme activity. To test whether this
      posttranslational effect involved the cytosolic phospholipase A2 (cPLA2) isoform,
      Western blots were probed for cPLA2 protein. Results indicated that IL stimulated
      cPLA2 activity and synthesis, which was inhibited by SB but not PD. These data
      indicate that (1) IL induction of iNOS synthesis depends on both the p42/44 and
      p38 signaling pathways, acting primarily at the level of transcriptional
      regulation; and (2) IL regulation of COX-2 synthesis involves the p42/44 and p38
      signaling pathways, with an additional level of regulation occurring
      posttranslationally, perhaps at the level of activation of the cPLA2 isoform,
      which may be involved in intracellular signaling, as well as regulation of
      arachidonic acid release for COX-2 activity.

PMID- 9931118
TI  - Interleukin-1beta regulation of the human brain natriuretic peptide promoter
      involves Ras-, Rac-, and p38 kinase-dependent pathways in cardiac myocytes.
AB  - Because both the brain natriuretic peptide (BNP) gene and the cytokine
      interleukin-1beta (IL-1beta) are induced in the infarcted myocardium, localized
      production of IL-1beta may regulate the BNP gene. We tested whether (1) IL-1beta
      regulates the human BNP promoter, (2) cis elements in the proximal promoter
      respond to IL-1beta, and (3) mitogen-activated protein kinase (MAPK) signaling
      pathways [p42/44, c-jun (JNK) and p38 kinase] are involved. We transferred the
      hBNP promoter coupled to a luciferase reporter gene or constructs with mutations
      in the proximal promoter GATA and M-CAT elements into neonatal rat ventricular
      myocytes and treated the cells with IL-1beta for 24 hours. IL-1beta-stimulated
      hBNP luciferase activity was eliminated by pretreatment with the transcription
      inhibitor actinomycin D. Both the p38 kinase inhibitor SB205380 (SB) and
      cotransfection of a dominant-negative mutant of p38 kinase reduced IL-1beta
      stimulation of the hBNP promoter. Dominant-negative mutants of Ras and Rac
      inhibited IL-1beta-stimulated hBNP luciferase activity by 64% and 90%,
      respectively. Constitutively active forms of Rac and MKK6, the immediate upstream
      activator of p38, were stimulatory; however, only the effect of MKK6 was
      inhibited by SB. Neither the p42/44 nor the JNK pathway was involved in the
      action of IL-1beta. Both IL-1beta and MKK6 activation of the hBNP promoter were
      partially reduced when the promoter contained a mutated M-CAT element. In
      summary, (1) IL-1beta is a transcriptional activator of the hBNP promoter; (2) IL
      1beta acts through a Ras-dependent pathway not coupled to activation of p42/44
      MAPK or JNK; (3) IL-1beta acts through a Rac-dependent pathway, but the
      downstream effector is not known; and (4) IL-1beta activation of p38 kinase is
      partially involved in regulation of the hBNP promoter, targeting the proximal M
      CAT element.

PMID- 9931119
TI  - Genes encoding atrial and brain natriuretic peptides as candidates for
      sensitivity to brain ischemia in stroke-prone hypertensive rats.
AB  - -Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain
      natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility
      to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously
      hypertensive rat (SHRSP). We performed structural and functional analyses of
      these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats
      from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the
      relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp
      and Bnp genes revealed no difference between the 2 strains. Expression studies in
      brain tissue showed no differences at baseline and at 24 hours after middle
      cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide
      (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of
      brain natriuretic peptide were significantly higher in the SHRSPGla as compared
      with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence
      interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium
      dependent relaxations to bradykinin or ANP in middle cerebral arteries from the
      SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries
      harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8;
      pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in
      situ hybridization allowed us to map the Anf marker in the telomeric position of
      rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16.
      These results exclude Anp and Bnp as candidate genes for the sensitivity to brain
      ischemia and pave the way to further congenic and physical mapping strategies.

PMID- 9931120
TI  - Novel cis element for tissue-specific transcription of rat platelet-derived
      growth factor beta-receptor gene.
AB  - Platelet-derived growth factor (PDGF) and its receptors are widely expressed in
      several tissues in the stage of cellular growth and development. In adulthood,
      PDGF beta-receptor (PDGFbetaR) is mainly detected in pathological conditions such
      as atherosclerotic lesions and injured vascular wall. The purpose of the present
      study was to elucidate the underlying mechanism of PDGFbetaR gene expression
      under pathological conditions in vascular smooth muscle cells (VSMC) and to
      identify the important cis elements responsible for tissue-specific gene
      transcription. Gel mobility shift assay and supershift assay indicated that the
      CCAAT motif located at -67 (C67) was mainly interacted with NF-YC, and this
      element drove the basal promoter activity of the gene as a putative promoter. On
      the other hand, another important sequence essential for the basal transcription
      was found at a 30-bp region (R30) spanning -150 to -121. To test whether R30
      actually regulates the tissue-specific transcription of PDGFbetaR gene,
      electromobility shift pattern was compared between VSMC and hepatoma cell line
      (HTC). We obtained the result that DNA-protein complex seen only in nuclear
      extracts from HTC suppressed the promoter activity in HTC in a tissue-specific
      manner. Furthermore, cis element decoy transfection experiments for C67 and R30
      also revealed that both elements were functionally important in mRNA expression
      of PDGFbetaR in VSMC. From these results, we concluded that the basal activity of
      PDGFbetaR gene expression was transactivated by the interaction or coordination
      of both C67 and R30, and the latter one mainly controlled the tissue-specific
      gene expression in VSMC.

PMID- 9931121
TI  - Transcriptional regulation of the rat renin gene by regulatory elements in intron
      I.
AB  - Renin catalyzes the rate-limiting step in the enzymatic cascade leading to the
      vasoactive peptide angiotensin II. Therefore, the activity of the renin
      angiotensin system in a tissue is regulated significantly at the level of
      transcription of the renin gene. Besides transcription factor binding sites in
      the promoter region, the renin genes of human and rat contain regulatory elements
      also in intron I. Inclusion of intron I in reporter gene constructs with the
      renin promoter leads to a marked down-regulation of gene expression in nonrenin
      expressing 293 human embryonic kidney cells but has hardly any effect in renin
      expressing L8 rat skeletal myoblasts. In combination with the cytomegalovirus
      immediate early gene promoter, the silencing occurs in both cell lines but is
      less pronounced in L8 cells. By partially deleting intron I in these constructs,
      we describe 5 negative (I-NRE) and 2 positive (I-PRE) regulatory elements
      responsible for these effects. Using gel-retardation and methylation-interference
      assays with 293-nuclear extracts, we detected a pseudo-palindromic protein
      binding sequence between position +159 and +171 relative to the transcriptional
      start site. Binding of transcription factors to this sequence may be important
      for the tissue-specific silencing of the renin gene outside the juxtaglomerular
      cells of the kidney.

PMID- 9931122
TI  - Effects of human prorenin in rats transgenic for human angiotensinogen.
AB  - The physiological role of prorenin is unknown; however, the possibility that
      prorenin inhibits renin locally has been suggested. We tested the hypothesis that
      prorenin may be an endogenous competitor for renin uptake in the tissue. We also
      investigated whether prorenin can be activated to active renin and affect mean
      arterial pressure (MAP). Isolated perfused hindquarters of rats transgenic for
      human angiotensinogen were infused with human renin and/or prorenin. The plateau
      phase of angiotensin (Ang) I release 15 minutes after cessation of infusions was
      used as a parameter for renin uptake. Renin (10 ng/mL for 15 minutes) caused
      sustained release of Ang I (153+/-16 fmol/mL). Coinfusion with a 15-fold excess
      of prorenin did not affect local Ang I formation (153+/-19 fmol/mL). Prorenin
      infusion alone showed no activation to active renin. In addition, we investigated
      MAP and plasma Ang II levels after injection of saline (DeltaMAP, -1+/-2 mm Hg;
      40+/-5 fmol/mL Ang II), 9 ng renin (DeltaMAP, +37+/-3 mm Hg; 378+/-39 fmol/mL),
      and 144 ng prorenin (DeltaMAP, +10+/-5 mm Hg; 61+/-5 fmol/mL) and the coinjection
      of renin and prorenin (DeltaMAP, +41+/-4 mm Hg; 305+/-23 fmol/mL) in anesthetized
      rats. The data show that prorenin was not activated to active renin and did not
      affect MAP in short-term experiments. Renin-induced Ang formation was not
      affected by prorenin. Renin may have been taken up specifically because of its
      physical and chemical properties or because of nonspecific sequestration in the
      extravascular space. We conclude that prorenin does not act as an endogenous
      antagonist for the long-lasting effects of renin in the vascular wall. Moreover,
      prorenin does not affect acute renin-related effects on blood pressure.

PMID- 9931123
TI  - Appropriate regulation of renin and blood pressure in 45-kb human renin/human
      angiotensinogen transgenic mice.
AB  - The renin-angiotensin system is normally subject to servo control mechanisms that
      suppress plasma renin levels in response to increased blood pressure and increase
      plasma renin levels when blood pressure falls. In most species, renin is rate
      limiting, and angiotensinogen circulates at a concentration close to the Km, so
      varying the concentration of either can affect the rate of angiotensin formation.
      However, only the plasma renin level responds to changes in blood pressure and
      sodium balance to maintain blood pressure homeostasis. Therefore, the high plasma
      human renin levels and the hypertension of mice and rats containing both human
      renin and angiotensinogen transgenes indicate inappropriate regulation of renin
      and blood pressure. These anomalies led us to develop new lines of transgenic
      mice with a longer human renin gene fragment (45 kb) than earlier lines (13 to 15
      kb). Unlike their predecessors, the 45-kb hREN mice secrete human renin only from
      the kidneys, and both the human and mouse renins respond appropriately to
      physiological stimuli. To determine whether blood pressure is also regulated
      appropriately, we crossed these new 45-kb hREN mice with mice containing the
      human angiotensinogen gene. All doubly transgenic mice were normotensive like
      their singly transgenic and nontransgenic littermates. Moreover, among doubly
      transgenic mice, both human and mouse plasma renin concentrations were suppressed
      relative to the singly transgenic 45-kb hREN mice. These findings demonstrate the
      importance of appropriate cell and tissue specificity of gene expression in
      constructing transgenic models and affirm the pivotal role played by renal renin
      secretion in blood pressure control.

PMID- 9931124
TI  - Estrogen regulation of angiotensin-converting enzyme mRNA.
AB  - Estrogen replacement therapy is cardioprotective in postmenopausal women;
      however, the precise molecular mechanisms for this modulation are not fully
      elucidated. We previously showed that chronic estrogen replacement therapy
      reduced angiotensin-converting enzyme (ACE) activity in tissue extracts and serum
      with an associated reduction in plasma angiotensin II. A reverse transcriptase
      polymerase chain reaction assay was developed to determine whether estrogen
      treatment regulates tissue ACE mRNA concentration. Total RNA was isolated from
      kidney cortex, kidney medulla, lung, and aorta of ovariectomized Sprague-Dawley
      rats after 21 days of chronic 17beta-estradiol replacement therapy (5 mg pellet
      per rat SC) or placebo. A marked decrease in densitometric intensity ratios of
      amplified ACE cDNA to elongation factor-1alpha control cDNA was observed in all
      tissues from placebo-treated rats compared with the estradiol-treated rats (renal
      cortex: 0.29+/-0.04 versus 0.14+/-0.02; renal medulla: 0. 37+/-0.04 versus 0.24+/
      0.03; lung: 4.49+/-0.37 versus 2.49+/-0.59; and aorta: 0.41+/-0.04 versus 0.29+/
      0.02; all P<0.05). A comparable reduction in ACE activity was detected in tissue
      extracts from kidney cortex, kidney medulla, and lung of hormone-treated animals.
      Incubation of purified rat lung ACE with 1 or 10 micromol/L 17beta-estradiol had
      no effect on enzyme activity. These results suggest that estrogen treatment
      regulates tissue ACE activity by reducing ACE mRNA concentrations. Thus, the
      beneficial cardiovascular effects of estrogen may be mediated in part by
      downregulation of ACE with a consequent reduction in the circulating levels of
      the vasoconstrictor angiotensin II, a decrease in the metabolism of the
      vasodilator bradykinin, and an increase in the production of the vasorelaxant
      angiotensin-(1-7).

PMID- 9931125
TI  - Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension
      in mice: do kinin B2 receptors play a role?
AB  - Kinins have been shown to play an important role in the cardioprotective effect
      of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However,
      it is controversial as to whether kinins oppose the hypertensinogenic effect of
      deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and
      whether they mediate both chronic antihypertensive and cardiac antihypertrophic
      effects of ACEi in hypertension. Using normal 129/SvEvTac mice and mice lacking
      the bradykinin B2 receptor gene (B2-KO), we investigated whether (1) the
      hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B2-KO
      mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi
      (ramipril, 4 mg. kg-1. d-1) are mediated by B2 receptors in aortic coarctation (6
      weeks)- and DOCA-salt (4 weeks)-induced hypertension. Before surgery, there was
      no difference between 129/SvEvTac and B2-KO mice in terms of blood pressure and
      heart weight, suggesting that kinins are not essential to maintaining normal
      blood pressure. DOCA-salt (volume expansion) or aortic coarctation (renin
      dependent) induced similar hypertension and left ventricular hypertrophy (LVH) in
      129/SvEvTac and B2-KO mice, suggesting that kinins do not play an essential role
      in the development of DOCA-salt- or aortic coarctation-induced hypertension. We
      found that B2 receptors mediate only the early (1 week) but not the late phase (4
      weeks) of the chronic hypotensive effect of ACEi in DOCA-salt hypertension. On
      the other hand, chronic ACE inhibition prevented the development of hypertension
      and LVH in both 129/SvEvTac and B2-KO mice given DOCA-salt or subjected to aortic
      coarctation, suggesting that kinins do not participate in the chronic
      antihypertensive and antihypertrophic effects of ACEi in these 2 models of
      hypertension. Thus, in mice, kinins acting via B2 receptors do not participate in
      (1) maintenance of normal basal blood pressure, (2) establishment and maintenance
      of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic
      antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and
      aortic coarctation hypertension.

PMID- 9931126
TI  - Angiotensin II type 1 receptor-mediated peroxide production in human macrophages.
AB  - Our previous experiments demonstrated upregulation of the renin-angiotensin
      system in macrophages, including angiotensin II type 1 (AT1) and type 2 (AT2)
      receptors, during transformation from monocytes. We investigated the role of
      angiotensin II in oxidative stress of monocytes/macrophages, which plays a role
      in the advance of atherosclerosis. THP1, a human monocytic leukemia cell line,
      was differentiated to macrophages by adding of phorbol 12-myristate 13-acetate
      for 24 hours. The intracellular production of peroxide was measured by a
      cytofluorometric assay with 2', 7'-dichlorofluorescein-diacetate with a flow
      cytometer scan. Peroxide was detected in monocytes and upregulated during the
      transformation to macrophages by 3.18+/-0.52 times in relative fluorescein of
      peak value (P<0.01). Angiotensin II (1 micromol/L) induced oxidative stress in
      macrophages, with the peak at 15 minutes by 451+/-223%, and returned to the
      control level within 1 hour. EC50 was 5.4x10(-9) mol/L. AT1 antagonist (CV11974,
      1 micromol/L) significantly decreased angiotensin II-induced oxidative stress in
      macrophages, but AT2 antagonist (PD123319, 1 micromol/L) did not. Of interest,
      AT1 antagonist also decreased basal levels of peroxide production in macrophages
      in a dose-dependent manner. These results suggest that upregulation of the
      expression of AT1 receptor in macrophages contributes in part to upregulation of
      peroxide production. AT1 receptor antagonists may be useful to suppress oxidative
      stress of macrophages in atherosclerotic lesions.

PMID- 9931127
TI  - Regulation of angiotensin II type 1 receptor mRNA and protein in angiotensin II
      induced hypertension.
AB  - Chronic elevations of circulating angiotensin II (Ang II) cause sustained
      hypertension and enhanced accumulation of intrarenal Ang II by an AT1 receptor
      dependent process. The present study tested the hypothesis that chronic
      elevations in circulating Ang II regulate AT1 mRNA and protein expression in a
      tissue-specific manner. Sprague-Dawley rats were infused with Ang II (80 ng/min)
      or vehicle subcutaneously for 13 days via osmotic minipump. On day 12, systolic
      blood pressure averaged 186+/-12 mm Hg in Ang II-infused rats compared with rats
      given vehicle (121+/-2 mm Hg). Plasma renin activity was markedly suppressed in
      the Ang II-infused rats compared with vehicle-infused rats (0.1+/-0.01 versus
      4.9+/-0.9 ng of Ang I. mL-1. h-1; P<0.05). Semiquantitative reverse transcription
      polymerase chain reaction using rat AT1A- and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH)-specific primers was followed by Southern blot
      hybridization using specific radiolabeled cDNA or oligonucleotide probes. The
      results showed that the ratios of AT1A/GAPDH mRNA in the kidney (0.19+/-0.05
      versus 0. 26+/-0.03) and liver (2.8+/-0.9 versus 3.0+/-0.5) were comparable in
      Ang II- and vehicle-infused rats. In contrast, AT1A/GAPDH mRNA levels were
      increased in the adrenal glands of Ang II-infused rats (0.49+/-0.04 versus 0.36+/
      0.02; P<0.05). Western blot analysis showed that AT1 protein levels in the kidney
      and liver were also similar in the two groups. Therefore, these results indicate
      that renal and liver AT1 receptor gene expression is maintained in Ang II-induced
      hypertension. The failure to downregulate AT1 receptor mRNA and protein levels
      thus allows the sustained effects of chronic elevations in Ang II to elicit
      progressive increases in arterial pressure.

PMID- 9931128
TI  - Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat
      kidney.
AB  - Adult Ren-2 gene transgenic rats, TGR(mRen-2)27, exhibit elevated circulating and
      kidney angiotensin II (Ang II) levels in the presence of severe hypertension. The
      aim of this study was to examine whether AT1 and AT2 receptors in the kidney and
      renal hemodynamic and tubular responses to blockade of these receptors were
      altered in the Ren-2 gene transgenic rats during the maintenance phase of
      hypertension. Renal AT1 and AT2 receptors were mapped by in vitro autoradiography
      (n=8), and the effects of blockade of these receptors on mean arterial pressure
      (MAP), heart rate (HR), and renal cortical (CBF) and medullary blood flows (MBF)
      were studied in anaesthetized, adult age-matched male homozygous TGR rats (n=12)
      and Sprague-Dawley (SD) rats (n=7). TGR rats showed higher basal MAP (P<0.001),
      heart and kidney weight (P<0.001), plasma renin activity (P<0.05) and plasma Ang
      II level (P<0.05), and CBF (P<0.05) and MBF (P<0.05) than SD rats. AT1 receptor
      binding was significantly increased in the glomeruli, proximal tubules, and the
      inner stripe of the outer medulla of TGR rats (P<0.01), while the AT2 receptor
      binding was low at all renal sites of TGR and SD rats. Immunohistochemistry
      revealed that this increased AT1 receptor labeling occurred mainly in vascular
      smooth muscle layer of intrarenal blood vessels including afferent and efferent
      arterioles, juxtaglomerular apparatus, glomerular mesangial cells, proximal
      tubular cells, and renomedullary interstitial cells (RMICs) in the transgenic
      rats. Blockade of AT1 receptors with losartan in TGR rats markedly reduced MAP to
      the normotensive level (P<0.001) without altering HR. Both CBF (P<0.005) and MBF
      (P<0.05) were significantly increased by losartan in the transgenic rats. By
      contrast, losartan only caused a smaller decrease in MAP and an increase in renal
      CBF in SD rats (P<0.05). PD 123319 was without any renal effect in both SD and
      TGR rats. These findings suggest that markedly increased AT1 receptors in renal
      vasculature, glomerular mesangial cells, and RMICs in the presence of fulminant
      hypertension and elevated circulating and tissue Ang II levels may play an
      important role in the maintenance of hypertension in the Ren-2 gene transgenic
      rats.

PMID- 9931129
TI  - Antisense inhibition of AT1 receptor in vascular smooth muscle cells using adeno
      associated virus-based vector.
AB  - Vascular smooth muscle cells (VSMCs) are the main peripheral target for
      vasoconstriction and growth-promoting activity of angiotensin II (Ang II), acting
      through angiotensin type 1 receptors (AT1-R). Current antihypertension treatments
      include daily reductions in the effects of Ang II. To decrease an effect of Ang
      II in a prolonged fashion, we have developed an adeno-associated virus (AAV)
      vector with antisense DNA for AT1-R. AAV has many advantages over other viral
      vectors. AAV is nonpathogenic, does not stimulate inflammation or immune reaction
      and enters nondividing cells, and provides stable long-term gene expression. To
      test AAV in VSMCs, we constructed and tested plasmid AAV (pAAV) and recombinant
      AAV (rAAV) with AT1-R antisense DNA. rAAV was constructed with a cassette
      containing a cytomegalovirus promoter and the cDNA for the AT1-R inserted in the
      antisense direction. The cassette was packaged into the virion. Transfection of
      VSMCs with the pAAV antisense to AT1-R produced a significant reduction in the
      amount of AT1-R (P<0.01). Transduction of VSMCs with the rAAV-AT1-R-AS at MOI of
      5 also showed significant reduction of AT1-R and long-lasting expression of the
      transgene for at least 8 weeks. The reduction of AT1-R number in VSMCs was
      concomitant with a decrease in the Ang II-stimulated increase of intracellular
      calcium. The results show that AAV vector delivers AT1-R antisense to inhibit AT1
      R in VSMCs. For the purpose of gene therapy for hypertension, it is necessary to
      demonstrate the effectiveness of a vector system in VSMCs. This study provides
      support for the potential use of AAV AT1-R antisense in VSMCs.

PMID- 9931130
TI  - Angiotensin II type 1 receptor antisense gene therapy prevents altered renal
      vascular calcium homeostasis in hypertension.
AB  - Intracellular Ca2+ ([Ca2+]i) homeostasis regulates vascular smooth muscle tone,
      and alteration in [Ca2+]i handling is associated with the development and
      establishment of hypertension. We have previously established in the
      spontaneously hypertensive rat (SHR) that virally mediated delivery of
      angiotensin II type 1 receptor antisense (AT1R-AS) prevents the development of
      high blood pressure and some pathophysiology associated with hypertension for 120
      days. In light of this, our objectives in this study were to determine whether
      AT1R-AS gene therapy (1) could have a longer duration in the prevention of
      hypertension and (2) would attenuate the alterations in renal vascular Ca2+
      homeostasis and therefore vasoconstriction, characteristics of hypertension.
      Intracardiac delivery of AT1R-AS in neonates prevented the development of
      hypertension in SHR for at least 210 days. At this time, untreated SHR renal
      resistance arterioles showed a significantly enhanced contractile response to KCl
      and angiotensin II (Ang II) when compared with normotensive Wistar-Kyoto rats. In
      addition, L-type Ca2+ current density and Ang II-dependent increases in [Ca2+]i
      were significantly increased in cells dissociated from renal resistance
      arterioles of the untreated SHR. AT1R-AS treatment prevented all of the above
      vascular alterations associated with the hypertensive state in SHR. Finally,
      Western blot analysis of L-type Ca2+ channel (alpha1C) protein levels in renal
      resistance arterioles of untreated SHR showed no significant difference when
      compared with control. These results are novel and demonstrate that viral
      mediated delivery of AT1R-AS not only attenuates the development of hypertension
      on a long-term basis but prevents changes in renal vascular Ca2+ homeostasis
      associated with the disease.

PMID- 9931131
TI  - Role of AT2 receptors in angiotensin II-stimulated contraction of small
      mesenteric arteries in young SHR.
AB  - This study assesses the receptor subtype (AT1 and AT2) through which angiotensin
      II (Ang II) mediates contraction in small arteries of young and adult
      spontaneously hypertensive rats (SHR). Segments of third-order mesenteric
      arteries ( approximately 200 microm in lumen diameter) were mounted in a
      pressurized system. Systolic blood pressure and media:lumen ratio of small
      arteries were significantly greater (P<0.001) in young SHR and adult SHR than in
      age-matched Wistar-Kyoto rats (WKY). Ang II-induced contractile effects were
      significantly increased (P<0.05) in young SHR compared with age-matched WKY. AT1
      blockade with losartan, and combined AT1 and AT2 blockade with losartan and
      PD123319, abolished Ang II-stimulated contraction in young and adult rats. AT2
      blockade (PD123319) significantly reduced (P<0.01) Ang II-elicited contraction in
      young SHR but had no effect in WKY or adult SHR, indicating that AT2 receptors
      may contribute to Ang II-induced contraction in young SHR. To determine the Ang
      receptor status in rat mesenteric vessels, AT1 and AT2 receptor mRNA expression
      was determined by reverse transcription-polymerase chain reaction. AT1 and AT2
      receptor protein expression were detected by Western blot analysis. AT1 receptor
      mRNA was equally expressed in age-matched rats, but expression was significantly
      lower in young rats compared with adult rats. AT2 receptor mRNA was weakly
      expressed in WKY and adult SHR. In vessels from young SHR, AT2 receptor mRNA
      expression was significantly increased compared with the other groups. AT1
      receptor protein was equally expressed in adult rats of both strains but was
      undetectable in young rats. AT2 receptor protein was only detectable in young
      rats, with the magnitude of expression greater in SHR than WKY. In conclusion,
      Ang II-stimulated contractile responses are augmented in vessels from young SHR.
      These effects are reduced by selective AT2 blockade and abolished by AT1
      blockade, indicating that both Ang receptor subtypes are involved in contraction
      in young SHR. In WKY and adult SHR, losartan, but not PD123319, inhibited Ang II
      induced contraction, indicating the exclusive involvement of AT1 receptors. Thus,
      in SHR, in the phase of developing hypertension, enhanced Ang II-stimulated
      vascular contraction may be associated with changes in Ang II receptor status, as
      evidenced pharmacologically and by increased vascular AT2 receptor mRNA and
      protein expression.

PMID- 9931132
TI  - Effects of angiotensin II on sodium potassium pumps, endogenous ouabain, and
      aldosterone in bovine zona glomerulosa cells.
AB  - Angiotensin (Ang) II stimulates secretions of aldosterone and an endogenous
      ouabain-like steroid (EO) from bovine adrenal zona glomerulosa (BAG) cells. The
      BAG cell sodium pump, a possible target of EO, affects aldosterone secretion
      although little is known about this pump. Here, we describe the effects of Ang II
      on the characteristics of this transporter and steroid secretions. Under serum
      free conditions, 3H-ouabain bound to a single class of sites on BAG cells.
      Binding of label was time and concentration dependent, was sensitive to
      extracellular potassium ions, and was displaced by ouabain and digoxin with EC50
      of approximately 218 and approximately 232 nmol/L, respectively. Sodium pump
      mediated 86Rb uptake was inhibited by ouabain (EC50 approximately 301 nmol/L).
      Ang II dose dependently augmented secretions of EO and aldosterone, increased
      ouabain-sensitive 86Rb uptake and 3H-ouabain binding, and increased the affinity
      for 3H-ouabain binding (Kd, from 205 to 80 nmol/L) with no change in the maximal
      number of sodium pumps (5.45x10(6)) per cell. Losartan blocked all effects of Ang
      II except EO secretion, which was inhibited by PD123319. We conclude that BAG
      cells express sodium pumps in high density and bind ouabain to a single class of
      low-affinity sites. The characteristics of the sodium pumps protect BAG cells
      from EO autotoxicity but may exclude them from mediating feedback inhibition of
      EO secretion. The effects of Ang II on sodium pump activity, ouabain binding
      affinity, and aldosterone secretion are mediated via Ang II type 1 receptors,
      whereas Ang II type 2 receptors augment EO secretion. The role of the Ang II
      mediated increase in the ouabain sensitivity of BAG cell sodium pumps in the
      secretions of aldosterone and EO remains to be elucidated.

PMID- 9931133
TI  - Angiotensin II signaling in vascular smooth muscle cells under high glucose
      conditions.
AB  - The mechanisms responsible for the accelerated cardiovascular disease in
      diabetes, as well as the increased hypertrophic effects of angiotensin II (Ang
      II) under hyperglycemic conditions, are not very clear. We examined whether the
      culture of vascular smooth muscle cells (VSMC) under hyperglycemic conditions to
      simulate the diabetic state can lead to increased activation of key growth- and
      stress-related kinases, such as the mitogen-activated protein kinases (MAPKs), in
      the basal state and in response to Ang II. Treatment of porcine VSMC for short
      time periods (0.5 to 3 hours) with high glucose (HG; 25 mmol/L) markedly
      increased the activation of the extracellular signal-regulated kinase (ERK1/2)
      and c-Jun/N-terminal kinase (JNK) relative to cells cultured in normal glucose
      (NG; 5.5 mmol/L). p38 MAPK also was activated by HG, and this effect remained
      sustained for several hours. Ang II treatment increased the activity of all 3
      families of MAPKs. Ang II-induced ERK activation was potentiated nearly 2-fold in
      cells treated with HG for 0.5 hour. However, Ang II-induced JNK was not altered.
      In VSMC cultured for 24 hours with HG, Ang II and HG displayed an additive
      response on p38 MAPK activity. MAPKs can lead to activation of transcription
      factors such as activator protein-1 (AP-1). HG alone significantly increased AP-1
      DNA-binding activity. Furthermore, Ang II and HG combined had additive effects on
      AP-1 activity. These results suggest that increased activation of specific MAPKs
      and downstream transcription factors, such as AP-1, may be key mechanisms for the
      increased VSMC growth potential of HG alone and of Ang II under HG conditions.

PMID- 9931134
TI  - Increased central angiotensin and osmotic responses in the Ren-2 transgenic rat.
AB  - We previously demonstrated that the Ren-2 transgenic (TG) rat is sensitive to
      salt, showing a sodium-induced pressor response. The present studies determined
      the effect of central stimulation with hypertonic saline (HS) and angiotensin II
      (Ang II) on mean arterial pressure (MAP), heart rate (HR), and plasma
      vasopressin. HS (1 mol/L NaCl, 5 microL) or Ang II (100 ng, 5 microL) was
      injected into the lateral ventricle of conscious male TG and control rats. The
      pressor responses to HS and Ang were greater in TG than in control rats,
      increases of 42+/-4 and 41+/-4 mm Hg versus 25+/-3 and 18+/-2 mm Hg (HS and Ang
      II and TG and control rats, respectively). The TG rats also showed an increased
      vasopressin response to Ang II, peak levels of 14+/-3 versus 28+/-3 pg/mL
      (control versus TG rats). HS increased plasma vasopressin levels, although the
      group responses were not different. HR was not significantly altered by either
      stimulus. Results demonstrate an increased responsiveness to intraventricular HS
      and Ang II in Ren-2 transgenic rats, suggesting a relationship between the
      enhanced angiotensinergic drive and central cardiovascular and vasopressin
      responses.

PMID- 9931135
TI  - Monocyte infiltration and adhesion molecules in a rat model of high human renin
      hypertension.
AB  - Hypertension and kidney damage in the double transgenic rat (dTGR) harboring both
      human renin and human angiotensinogen genes are dependent on the human components
      of the renin angiotensin system. We tested the hypothesis that monocyte
      infiltration and increased adhesion molecule expression are involved in the
      pathogenesis of kidney damage in dTGR. We also evaluated the effects of long-term
      angiotensin-converting enzyme (ACE) inhibition, AT1 blockade, and human renin
      inhibition on monocyte recruitment and inflammatory response in dTGR. Systolic
      blood pressure and 24-hour albuminuria were markedly increased in 7-week-old dTGR
      as compared with age-matched normotensive Sprague Dawley rats. We found a
      significant monocyte/macrophage infiltration in the renal perivascular space and
      increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) in the interstitium, intima, and adventitia of
      the small renal vessels. alphaLbeta2 integrin and alpha4beta1 integrin, the
      corresponding ligands for ICAM-1 and VCAM-1, were also found on infiltrating
      monocytes/macrophages. The expression of plasminogen activator inhibitor-1 and
      fibronectin in the kidneys of dTGR were increased and distributed similarly to
      ICAM-1. In 4-week-old dTGR, long-term treatment with ACE inhibition (cilazapril),
      AT1 receptor blockade (valsartan), and human renin inhibition (RO 65-7219) (each
      drug 10 mg/kg by gavage once a day for 3 weeks) completely prevented the
      development of albuminuria. However, only cilazapril and valsartan were able to
      decrease blood pressure to normotensive levels. Interestingly, the drugs were all
      equally effective in preventing monocyte/macrophage infiltration and the
      overexpression of adhesion molecules, plasminogen activator inhibitor-1, and
      fibronectin in the kidney. Our findings indicate that angiotensin II causes
      monocyte recruitment and vascular inflammatory response in the kidney by blood
      pressure-dependent and blood pressure-independent mechanisms. ACE inhibition, AT1
      receptor blockade, and human renin inhibition all prevent monocyte/macrophage
      infiltration and increased adhesion molecule expression in the kidneys of dTGR.

PMID- 9931136
TI  - Bbeta-adrenergic receptor kinase-1 levels in catecholamine-induced myocardial
      hypertrophy: regulation by beta- but not alpha1-adrenergic stimulation.
AB  - Pressure overload ventricular hypertrophy is accompanied by dysfunctional beta
      adrenergic receptor signaling due to increased levels of the beta-adrenergic
      receptor kinase-1, which phosphorylates and desensitizes beta-adrenergic
      receptors. In this study, we examined whether increased beta-adrenergic receptor
      kinase 1 expression is associated with myocardial hypertrophy induced by
      adrenergic stimulation. With use of implanted mini-osmotic pumps, we treated mice
      with isoproterenol, phenylephrine, or vehicle to distinguish between alpha1- and
      beta-adrenergic stimulation. Both treatments resulted in cardiac hypertrophy, but
      only isoproterenol induced significant increases in beta-adrenergic receptor
      kinase-1 protein levels and activity. Similarly, in isolated adult rat cardiac
      myocytes, 24 hours of isoproterenol stimulation resulted in a significant 2.8
      fold increase in beta-adrenergic receptor kinase-1 protein levels, whereas 24
      hours of phenylephrine treatment did not alter beta-adrenergic receptor kinase-1
      expression. Our results indicate that increased beta-adrenergic receptor kinase-1
      is not invariably associated with myocardial hypertrophy but apparently is
      controlled by the state of beta-adrenergic receptor activation.

PMID- 9931137
TI  - The myocardial beta-adrenergic system in spontaneously hypertensive heart failure
      (SHHF) rats.
AB  - -Responsiveness to beta-adrenergic stimulation is reduced in the failing human
      myocardium. This results principally from reduced beta-adrenergic receptor
      (betaAR) density, elevated beta-adrenergic receptor kinase 1 (betaARK1) levels,
      and functional uncoupling of remaining receptors. The temporal nature of changes
      in the human myocardial beta-adrenergic system relative to onset of symptomatic
      heart failure (HF) has been difficult to discern. A relatively new model of HF,
      the spontaneously hypertensive heart failure (SHHF) rat spontaneously and
      reproducibly develops left ventricular hypertrophy (LVH) and progresses to HF,
      thus enabling longitudinal studies to examine the cellular and molecular bases
      for hypertension-induced cardiac hypertrophy and subsequent HF. The purpose of
      this study was to examine age-dependent changes in the betaAR system in this
      model. Lean male SHHF rats at 3, 7, 14, and 20 months were compared with age
      matched Sprague-Dawley (SD) control rats ([C]; 4 animals/group). At all ages the
      SHHF rats had elevated blood pressures and left ventricular end-diastolic
      pressure relative to the SD control rats (P<0.05). Compared with age-matched SD
      control rats, LVH was evident by 3 months in SHHF rats; 20-month-old SHHF rats
      had significantly greater LVH compared with the other SHHF rat groups. beta
      adrenergic responsiveness (maximal heart rate to isoproterenol) was reduced only
      in 20-month-old SHHF rats. betaARK1 protein levels and activity were elevated at
      14 months (162+/-10% and 195+/-20% C, respectively), and betaARK1 protein
      remained elevated at 20 months (140+/-14% C). In contrast, G protein-coupled
      receptor kinase 5, a second receptor kinase in the heart, remained unchanged at
      all ages. betaAR density did not change with age in the SD control rats and was
      similar in the SHHF rats until 20 months of age when the receptor number was
      reduced (30+/-1%). These data indicate that cardiac dysfunction is coincident
      with reduced betaAR density. Importantly, cardiac dysfunction was preceded by
      elevated betaARK1 levels and activity, thus suggesting that betaARK1 may be a
      precipitating factor in the transition from hypertension-induced compensatory
      cardiac hypertrophy to HF. Furthermore, these results indicate that the SHHF rat
      is a powerful model for use in examination of the mechanisms involved in
      alterations of beta-adrenergic signaling that occur in human HF.

PMID- 9931138
TI  - Afferent arteriolar vasodilation to the sulfonimide analog of 11, 12
      epoxyeicosatrienoic acid involves protein kinase A.
AB  - The current study determined the contribution of protein kinase-A (PKA) and
      protein kinase-G (PKG) to the vasodilation elicited by the N-methylsulfonimide
      analog of 11,12-epoxyeicosatrienoic acid (11, 12-EET). Experiments were
      performed, in vitro, using the juxtamedullary nephron preparation combined with
      videomicroscopy. The response of afferent arterioles to the sulfonimide analog of
      11, 12-EET, was determined before and after inhibition of PKA, PKG, or guanylyl
      cyclase. Afferent arterioles, preconstricted with 0.5 micromol/L norepinephrine,
      averaged 18+/-1 microm (n=25) at a renal perfusion pressure of 100 mm Hg.
      Superfusion with 0.01 to 100 nmol/L of the 11,12-EET analog caused a graded
      increase in diameter of the afferent arteriole. Vessel diameter increased by 11+/
      1% and 15+/-1%, respectively, in response to 10 and 100 nmol/L of the 11,12-EET
      analog. The afferent arteriolar response to 10 and 100 nmol/L of the 11,12-EET
      analog was significantly attenuated during inhibition of PKA with 10 micromol/L H
      89 (n=7) or 5 micromol/L myristolated PKI (n=6), such that afferent arteriolar
      diameter increased by only 5+/-2% and 2+/-1%, respectively, in response to 100
      nmol/L of the 11, 12-EET analog. In contrast, the afferent arteriolar
      vasodilatory response to the 11,12-EET analog was unaffected by PKG or guanylyl
      cyclase inhibition. In the presence of 200 micromol/L histone H2B (n=5) or 10
      micromol/L ODQ (n=7), the afferent arteriolar diameter increased by 16+/-3% and
      12+/-2%, respectively, in response to 100 nmol/L of the 11,12-EET analog. These
      results demonstrate that activation of PKA is an important mechanism responsible
      for the afferent arteriolar vasodilation elicited by the sulfonimide analog of
      11,12-EET.

PMID- 9931139
TI  - Role of tyrosine kinase and PKC in the vasoconstrictor response to 20-HETE in
      renal arterioles.
AB  - The present study examined the hypothesis that activation of protein kinase C
      (PKC), components of the mitogen-activated protein (MAP) kinase pathway, or both
      contributes to the inhibitory effects of 20-hydroxyeicosatetraenoic acid (20
      HETE) on K+-channel activity and its vasoconstrictor response in renal
      arterioles. 20-HETE (0.1 to 50 micromol/L) dose-dependently produced a 30%
      increase in PKC activity and a fivefold rise in the expression of active
      extracellular signal-regulated kinase 1 (ERK1) and ERK2 proteins in renal
      microvessels. 20-HETE (0.01 to 1 micromol/L) reduced the diameter of isolated
      perfused renal interlobular arterioles by 33+/-2%. Blockade of PKC activity with
      an N-myristoylated PKC pseudosubstrate inhibitor (Myr-PKCi, 100 micromol/L) or
      calphostin C (0.5 micromol/L) had no significant effect on the vasoconstrictor
      response to 20-HETE. In contrast, the tyrosine kinase inhibitors genistein (30
      micromol/L) and tyrphostin 25 (10 micromol/L) reduced the response to 20-HETE by
      76.5+/-2.1% and 67.5+/-1.8%, respectively. A specific inhibitor of mitogen
      activated extracellular signal-regulated kinase (MEK), PD98059, had no effect on
      the vasoconstrictor response to 20-HETE. In cell-attached patches on renal
      vascular smooth muscle cells, 20-HETE reduced the open state probability of a
      large-conductance K+ channel (from 0.0026+/-0.0004 to 0.0006+/-0.0001). The Myr
      PKCi (100 micromol/L) did not alter the inhibitory effects of 20-HETE on this
      channel. In contrast, the tyrosine kinase inhibitor genistein (30 micromol/L)
      blocked the inhibitory effects of 20-HETE on the large-conductance K+ channel.
      These data suggest that 20-HETE activates the MAP kinase system in renal
      arterioles and that the activation of a tyrosine kinase, which is proximal to MEK
      in this cascade, contributes to the inhibitory effects of 20-HETE on K+-channel
      activity and its vasoconstrictor effects in the renal arterioles.

PMID- 9931140
TI  - Role of 20-HETE in elevating chloride transport in the thick ascending limb of
      Dahl SS/Jr rats.
AB  - This study examined the role of endogenous 20 hydroxyeicosatetraenoic acid (20
      HETE) in elevating Cl- transport in the medullary thick ascending loop of Henle
      (MTAL) of 9-week-old male Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr)
      rats perfused in vitro. Basal transepithelial voltage (Vte; 14.9+/-0.9 versus
      10.1+/-0.5 mV) and net lumen-to-bath Cl- flux (JCl) (155+/-6 versus 127+/-5 pEq.
      min-1. mm-1) were significantly greater in MTAL isolated from SS/Jr rats (n=16)
      than in those obtained from SR/Jr rats (n=16). Blockade of the synthesis of 20
      HETE with 17-octadecynoic acid (17-ODYA; 10 micromol/L) increased Vte from 9. 9+/
      0.8 to 13.1+/-1.0 mV and JCl from 127+/-7 to 152+/-8 pEq. min-1. mm-1 in the MTAL
      of SR/Jr rats (n=8), but it had no significant effect on Vte or JCl in the MTAL
      of SS/Jr rats (n=8). Exogenous 20-HETE (1 micromol/L) decreased Vte from 14.8+/
      0.6 to 10.5+/-0.6 mV and JCl from 155+/-10 to 116+/-6 pEq. min-1. mm-1 in MTAL of
      SS/Jr rats (n=8), but it had no effect on Vte or JCl in the MTAL of SR/Jr rats
      (n=8). The expression of P4504A2 protein in the MTAL of SS/Jr rats was
      approximately half of that seen in the MTAL of SR/Jr rats. These results indicate
      that endogenously formed 20-HETE regulates transepithelial voltage and Cl-
      transport in the MTAL and that a diminished production of 20-HETE contributes to
      an elevation in Cl- transport in the MTAL of SS/Jr rats.

PMID- 9931141
TI  - Two-week administration of tempol attenuates both hypertension and renal
      excretion of 8-Iso prostaglandin f2alpha.
AB  - 8-Iso prostaglandin F2alpha (8-ISO) is formed nonenzymatically from the attack of
      superoxide radical on arachidonic acid. Therefore, 8-ISO is a marker of oxidative
      stress in vivo. We have recently shown that short-term administration of the
      membrane-permeable, metal-independent superoxide dismutase mimetic tempol (4
      hydroxy-2, 2, 6, 6-tetramethyl piperidinoxyl) normalizes blood pressure in
      spontaneously hypertensive rats (SHR). The present study was designed to test
      whether prolonged administration of tempol ameliorates oxidative stress and
      hypertension in SHR. In control SHR (n=8), mean arterial pressure and heart rate
      were increased and renal blood flow and glomerular filtration rate were reduced
      compared with control Wistar-Kyoto rats (WKY) (n=7). Twenty-four-hour renal
      excretion of 8-ISO was significantly increased in SHR compared with WKY. Two
      weeks of tempol administration in the drinking water (1 mmol/L) to SHR (n=8)
      decreased mean arterial pressure by 18% (162+/-8 to 134+/-6 mm Hg, P<0.05),
      increased glomerular filtration rate by 17% (1.6+/-0.2 to 1. 9+/-0.3 mL/min), and
      decreased renal excretion of 8-ISO by 39% (9. 8+/-0.7 to 6.0+/-0.7 ng/24 hours,
      P<0.05). In contrast, tempol administration to WKY (n=6) had no significant
      effect on mean arterial pressure (115+/-5 versus 118+/-8 mm Hg), glomerular
      filtration rate (3.0+/-0.4 versus 2.5+/-0.5 mL/min), or renal excretion of 8-ISO
      (7.9+/-0.4 versus 6.8+/-0.7 ng/24 hours). In conclusion, the SHR is a model of
      hypertension and renal vasoconstriction associated with oxidative stress. Because
      long-term administration of a superoxide scavenger reduces blood pressure and
      oxidative stress in vivo, this study suggests a role for oxygen radicals in the
      maintenance of hypertension in SHR.

PMID- 9931142
TI  - Mesenteric vasodilation mediated by endothelial anandamide receptors.
AB  - Cannabinoids, including the endogenous ligand anandamide (arachidonyl
      ethanolamide), elicit pronounced hypotension in rats via activation of
      peripherally located CB1 cannabinoid receptors, which have been also implicated
      in endotoxin (lipopolysaccharide [LPS])-induced hypotension. The present study
      was designed to test the role of vascular CB1 receptors in cannabinoid- and
      endotoxin-induced mesenteric vasodilation. In the isolated, buffer-perfused rat
      mesenteric arterial bed precontracted with phenylephrine, anandamide induced long
      lasting (up to 60 minutes) dose-dependent vasodilation (ED50: 79+/-3 nmol;
      maximal relaxation: 77+/-2%), inhibited by 0.5 to 5.0 micromol/L of the selective
      CB1 receptor antagonist SR141716A. Low doses of the calcium ionophore ionomycin
      also caused mesenteric vasodilation inhibited by SR141716A. The metabolically
      stable analogue R-methanandamide elicited mesenteric vasodilation (ED50: 286+/-29
      nmol), whereas the potent synthetic CB1 receptor agonists WIN 55212-2 and HU-210
      caused no change in vascular tone or only a minor dilator effect not affected by
      SR141716A, respectively. The endogenous ligand 2-arachidonyl glycerol caused no
      change in vascular tone, whereas Delta9-tetrahydrocannabinol and arachidonic acid
      caused mesenteric vasoconstriction. After endothelial denudation, the dilator
      response to anandamide was slightly reduced and was no longer inhibited by
      SR141716A. In preparations from LPS-pretreated rats, SR141716A alone caused a
      significant and prolonged increase in perfusion pressure, whereas it had no such
      effect in control preparations perfused in vitro with or without LPS or after
      endothelial denudation in preparations from rats pretreated with LPS. We conclude
      that anandamide-induced mesenteric vasodilation is mediated by an endothelially
      located SR141716A-sensitive "anandamide receptor" distinct from CB1 cannabinoid
      receptors and that activation of such receptors by an endocannabinoid, possibly
      anandamide, contributes to LPS-induced mesenteric vasodilation in vivo.

PMID- 9931143
TI  - Differential expression of renal nitric oxide synthase isoforms during pregnancy
      in rats.
AB  - Alterations in nitric oxide (NO) production have been suggested to play a role in
      mediating changes in renal function during normal pregnancy and in pregnancy
      induced hypertension. Although NO production is enhanced during normal pregnancy,
      the mechanisms for the increase are unknown. The purpose of this study was to
      determine whether the elevation in NO production during pregnancy is associated
      with increases in renal expression of endothelial (eNOS), inducible (iNOS), and
      neuronal (nNOS) nitric oxide synthases. To achieve this goal we examined systemic
      and renal hemodynamics, urinary excretion of nitrate/nitrite, and renal protein
      expression of the three NOS isoforms in prepregnant rats, pregnant rats at days
      6, 13, and 19 of gestation and at day 4 postpartum. Mean arterial pressure
      decreased by 14% in late pregnancy whereas the glomerular filtration rate and
      renal plasma flow increased by 21% and 24%, respectively, in mid pregnancy.
      Excretion of nitrate/nitrite increased throughout pregnancy with a 3.4-fold
      increase present at day 19 (12.2+/-0.7 to 41.1+/-1.3 micromol/24 h). Renal eNOS
      protein expression decreased by 39% during pregnancy with the lowest level
      resulting at day 19 and returning to virgin levels by day 4 post partum. In
      contrast, renal iNOS and nNOS protein expression increased 31% and 25%,
      respectively, with highest expression occurring for both at day 13 of pregnancy.
      These data suggest that the increased NO production and renal hemodynamics
      associated with pregnancy in rats may be caused by the upregulation of iNOS and
      nNOS in the kidney.

PMID- 9931144
TI  - Local renal medullary L-NAME infusion enhances the effect of long-term
      angiotensin II treatment.
AB  - We hypothesized that the relatively high doses of angiotensin (Ang) II required
      to produce hypertension in rats were related to stimulation of renal medullary
      nitric oxide production, which in turn blunted reductions in medullary blood flow
      and the development of hypertension. Ang II was infused (5 days at 3 ng. kg-1.
      min-1 IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of
      a continuous medullary interstitial NG-nitro-L-arginine methyl ester (L-NAME)
      infusion. Renal cortical and medullary blood flows were determined with the use
      of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of
      medullary nitric oxide synthase inhibition did not change cortical or medullary
      blood flow or mean arterial pressure. A threshold dose of L-NAME was determined
      (75 microg. kg-1. h-1) that did not produce significant short- or long-term
      changes in medullary blood flow and mean arterial pressure. In rats with blunted
      medullary nitric oxide synthase activity, Ang II infused intravenously resulted
      in a 30% reduction in medullary blood flow (from 1.3 to 0.9+/-0.2V) and
      approximately 20 mm Hg increase in mean arterial pressure with Ang II infusion
      over 5 days. During 70 minutes after the start of intravenous Ang II, there was
      an immediate reduction in medullary blood flow, with no changes in cortical blood
      flow or mean arterial pressure. We conclude that the relative insensitivity of
      rats to long-term elevations of circulating Ang II is due to the potent
      counterregulatory actions of the nitric oxide system, specifically within the
      renal medulla. The results provide novel insights of how the organism attempts to
      protect itself from the hypertensive effects of Ang II.

PMID- 9931145
TI  - Renal intramedullary infusion of L-arginine prevents reduction of medullary blood
      flow and hypertension in Dahl salt-sensitive rats.
AB  - A role for reduced renal nitric oxide production has been proposed as a mechanism
      responsible for hypertension in Dahl "salt-sensitive" rats. The present study had
      2 goals: first, to determine the relationship between changes in mean arterial
      pressure and renal cortical and medullary blood flows in unanesthetized Dahl/Rapp
      salt-sensitive (S) and Dahl/Rapp salt-resistant (R) rats as daily salt intake was
      increased from 0.4% to 4.0%; second, to determine if delivery of L- or D-arginine
      into the renal medulla of Dahl S rats would change the responses to high salt.
      Optical fibers were implanted into the renal cortex and inner medulla for daily
      recording of cortical and medullary blood flows using laser-Doppler flowmetry.
      Indwelling aortic catheters were used to record arterial pressure. Increasing
      salt intake to 4.0% in Dahl S rats increased mean arterial pressure from 128+/
      2.0 to 155+/-5.0 mm Hg by day 5 of high salt diet; medullary blood flow was
      reduced 13% by day 2, 24% by day 3 (P<0.05), and 31% by day 5 (P<0.05), whereas
      cortical blood flow was unchanged. In Dahl R rats, mean arterial pressure
      averaged 117+/-5 mm Hg during the 0.4% salt control period and remained unchanged
      (as did cortical and medullary blood flows) during 5 days of 4.0% salt intake.
      Dahl S rats that received medullary L-arginine (300 microg. kg-1. min-1)
      exhibited no changes of mean arterial pressure or regional renal blood flow
      during the 5 days of 4.0% salt intake. Medullary infusion of D-arginine (300
      microg. kg-1. min-1) did not prevent the development of hypertension in Dahl S
      rats that received 4.0% salt. The results are consistent with the view that Dahl
      S rats have a reduced capacity to generate nitric oxide within the renal medulla
      under conditions of high salt, which the administration of L-arginine can
      normalize. Furthermore, early reductions of medullary blood flow in Dahl S rats
      with high salt intake probably contribute to the development of hypertension.

PMID- 9931146
TI  - Prolonged L-arginine on cardiovascular mass and myocardial hemodynamics and
      collagen in aged spontaneously hypertensive rats and normal rats.
AB  - This study was designed to examine whether L-arginine could prevent hypertension-
      and age-related impairment of coronary hemodynamics and cardiac fibrosis in aged
      (80-week-old) rats. To differentiate between hypertension- and age-related
      changes, the study was performed in both normotensive Wistar-Kyoto rats (WKYs)
      and spontaneously hypertensive rats (SHR). Male 1-year-old rats of both strains
      were divided into 2 groups and given either placebo or L-arginine (1.2 g/L) in
      drinking water. After 6 months, systemic and coronary hemodynamics (radionuclide
      labeled microspheres), right and left ventricular and aortic mass indexes, and
      ventricular hydroxyproline (an estimate of collagen) concentrations were
      determined. In the aged WKYs, L-arginine did not affect any of the examined
      variables except slightly reducing total peripheral resistance. In contrast, L
      arginine diminished arterial pressure, total peripheral resistance, and left
      ventricular and aortic mass indexes in the SHRs; it also increased coronary flow
      reserve and reduced minimal coronary flow resistance and myocardial
      hydroxyproline concentration. These findings demonstrated that L-arginine
      ameliorated adverse cardiovascular effects of hypertension in aged SHRs, as
      demonstrated by reduced arterial pressure and total peripheral resistance,
      diminished left ventricular mass and collagen content, and improved coronary
      hemodynamics. There were no important effects in the old WKYs.

PMID- 9931147
TI  - Role of neuronal nitric oxide synthase in Dahl salt-sensitive hypertension.
AB  - The goal of this study was to determine the role of neuronal nitric oxide
      synthase (nNOS) in the arterial pressure, renal hemodynamic, and renal excretory
      changes that occur in Dahl salt-resistant (DR) and salt-sensitive (DS) rats
      during changes in Na intake. Fifty-three DR and DS rats/Rapp strain of 7 to 8
      weeks of age with indwelling arterial and venous catheters were subjected to low
      (0.87 mmol/d) or high (20.6 mmol/d) Na intake beginning 2 days before the start
      of the control period. Measurements were made during a 5-day control period
      followed by a 5-day period of nNOS inhibition with intravenous 7-nitroindazole
      (7NI, 1.67 mg. kg-1. h-1) or vehicle infusion. After 5 days of 7NI, mean arterial
      pressure increased to 120+/-6% control in the DR-high Na, 7NI rats compared with
      98+/-1% control (P<0.05) in the DR-high Na alone rats. After 5 days of 7NI, DS
      high Na rats, which had a control arterial pressure 31 mm Hg higher than the
      comparable DR rats, increased their arterial pressure to 114+/-3% control, which
      was not significantly different from the DS-high Na alone pressure of 110+/-2%
      control. No significant changes occurred in glomerular filtration rate, effective
      renal plasma flow, urinary Na excretion, or urine volume because of 7NI. However,
      plasma renin activity decreased significantly in DR and DS rats on low Na intake
      with 7NI infusion. The data demonstrate that the highly salt-resistant DR rat
      became salt-sensitive during nNOS inhibition with 7NI. However, the arterial
      pressure of the DS rat was not affected by 7NI. This suggests that nitric oxide
      produced by nNOS in the DR rat normally helps to prevent salt-sensitive
      hypertension and that low functional levels of nNOS in the DS rat may contribute
      to its salt-sensitivity.

PMID- 9931148
TI  - Neuronal nitric oxide synthase-dependent afferent arteriolar function in
      angiotensin II-induced hypertension.
AB  - This study was designed to determine the influence of neuronal nitric oxide
      synthase (nNOS) in tubular flow-dependent regulation of afferent arteriolar
      diameter in hypertensive Sprague-Dawley rats that received 60 ng/min angiotensin
      II (Ang II) subcutaneously for 13 days. Systolic blood pressure of control and
      Ang II-infused rats averaged 122+/-2 (n=23) and 194+/-2 mm Hg (n=24). Afferent
      arteriolar responses to the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.1
      to 10 micromol/L) and the nonselective NOS inhibitor Nomega-nitro-L-arginine (L
      NNA; 1 to 100 micromol/L) were assessed in vitro using the blood-perfused
      juxtamedullary nephron preparation. At a perfusion pressure of 160 mm Hg,
      afferent arteriolar diameters from control and Ang II-infused rats averaged
      18.7+/-1.1 microm (n=8) and 18.1+/-1.1 microm (n=9), respectively, and decreased
      by 19. 9+/-1.5% and 11.8+/-1.1%, respectively, in response to 10 micromol/L L
      SMTC. The L-SMTC-induced afferent arteriolar constriction was significantly
      greater in control than in Ang II-infused rats. In contrast, 100 micromol/L L-NNA
      constricted afferent arterioles similarly in both control (n=8) and Ang II
      infused (n=7) rats. After transection of the loops of Henle to interrupt flow to
      the macula densa, the vasoconstrictor responses to L-SMTC but not to L-NNA were
      reversed. Increasing distal volume delivery by addition of 10 mmol/L
      acetazolamide to the blood perfusate significantly enhanced the afferent
      arteriolar constrictor responses to 10 micromol/L L-SMTC (34.5+/-4.8%, n=7) in
      normotensive rats. In contrast, in Ang II-infused rats, acetazolamide treatment
      did not enhance the responses to L-SMTC (n=8). These results indicate that
      chronic Ang II infusion reduces the ability of nNOS-derived nitric oxide to
      counteract the afferent arteriolar response to increased distal tubular flow.

PMID- 9931149
TI  - Effects of vasodilatory beta-adrenoceptor antagonists on endothelium-derived
      nitric oxide release in rat kidney.
AB  - The mechanisms for the vascular actions of vasodilatory beta-blockers remain
      undetermined. For some kinds of beta-blockers, the involvement of nitric oxide
      (NO) has been suggested. We studied the effects of vasodilatory beta-blockers on
      renal perfusion pressure (RPP) and NO release in the rat kidney. Infusion of
      bopindolol, celiprolol, and nebivolol caused a dose-dependent reduction in RPP
      and an increase in NO release (RPP: bopindolol 10(-6) mol/L, -23+/-2%; celiprolol
      10(-4) mol/L, -27+/-2%; nebivolol 10(-5) mol/L, -35+/-3%; NO: bopindolol 10(-6)
      mol/L, +33+/-2; celiprolol 10(-4) mol/L, +41+/-2; nebivolol 10(-5) mol/L, +45+/-5
      fmol. min-1. g kidney-1, mean+/-SEM). Metergoline (10(-6) mol/L), a 5
      hydroxytryptamine (5-HT)1/2 antagonist, or NAN-190 (10(-6) mol/L), a 5-HT1A
      antagonist, almost completely abolished the vasorelaxation and NO release caused
      by bopindolol, celiprolol, and nebivolol. However, neither propranolol nor
      bisoprolol decreased RPP. Celiprolol and nebivolol caused vasodilation in the rat
      thoracic aorta, and it was markedly reduced by endothelial denudation, Nomega
      nitro-L-arginine methyl ester (10(-4) mol/L), or NAN-190 (10(-6) mol/L). In
      deoxycorticosterone acetate-salt hypertensive rats, 4-week administration of
      celiprolol (50 mg. kg-1. d-1 IV) restored the responses regarding RPP and NO
      release to acetylcholine. These results suggest that several beta-blockers exert
      their vasodilatory action through the 5-HT1A receptor/NO pathway and that
      treatment with these beta-blockers may protect against endothelial injury in
      hypertension.

PMID- 9931150
TI  - Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously
      hypertensive rats.
AB  - This study tested the hypothesis that decreased responsiveness of renal
      mechanosensitive neurons constitutes an intermediate phenotype in spontaneously
      hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would
      contribute to increased renal sympathetic nerve activity and sodium retention,
      characteristic findings in hypertension. A backcross population, developed by
      mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a
      cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks
      from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40
      mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure
      and afferent renal nerve activity were determined. Mean arterial pressure ranged
      from 110 to 212 mm Hg and was inversely correlated with the magnitude of the
      increase in afferent renal nerve activity during increased ureteral pressure.
      Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated
      with hypertension in this backcross population. This aspect of the complex
      quantitative trait of altered renal sympathetic neural control of renal function,
      ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate
      phenotype in SHR.

PMID- 9931151
TI  - Effect of sinoaortic deafferentation on renal wrap hypertension.
AB  - The purpose of this study was to determine whether sinoaortic deafferentation
      (SAD) alters the severity of hypertension or sympathoadrenal contribution to mean
      blood pressure (MAP) during renal wrap hypertension. Male Sprague-Dawley rats
      were implanted with radiotelemetry transmitters for 24-hour recording of MAP and
      heart rate. All rats underwent either SAD or sham SAD (Intact) surgery and were
      allowed to recover for 10 to 14 days. The rats were then assigned to a
      normotensive (Sham) group or a hypertensive (Wrap) group in which 1-kidney figure
      8 renal wrap was performed. SAD increased the acute MAP response to renal wrap
      (Intact-Sham=5+/-1 mm Hg, Intact-Wrap=45+/-3 mm Hg, SAD-Sham=3+/-3 mm Hg, SAD
      Wrap=58+/-4 mm Hg) and increased the lability of MAP (SD of MAP; Intact
      Sham=3.8+/-0.2, Intact-Wrap=4.2+/-0.3, SAD-Sham=9. 6+/-1.4, SAD-Wrap=9.7+/-1.4).
      MAP was not different between SAD and Intact rats during 4 weeks after renal wrap
      or sham surgery; however, induction of hypertension produced additional MAP
      variability that was independent of SAD (Intact-Sham=4.6+/-0.4, Intact-Wrap=6.2+/
      0.6, SAD-Sham=6.3+/-0.5, SAD-Wrap=10.8+/-1.5). In a separate group of rats, the
      sympathoadrenal contribution to MAP was assessed by the depressor response to
      ganglionic blockade and plasma norepinephrine at rest and after neuronal uptake
      inhibition with desipramine. The depressor response to ganglionic blockade was
      significantly increased by renal wrap and by SAD (Intact-Sham=-49+/-2 mm Hg,
      Intact-Wrap=-73+/-4 mm Hg, SAD-Sham=-77+/-5 mm Hg, SAD-Wrap=-96+/-6 mm Hg). In
      the 3 groups with enhanced ganglionic blockade responses, desipramine caused a
      significant increase in plasma norepinephrine. These results indicate that SAD
      does not alter the development of renal wrap hypertension but does increase the
      sympathoadrenal contribution to MAP in both normotensive and hypertensive
      animals.

PMID- 9931152
TI  - Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a
      receptor.
AB  - Angiotensin (Ang) type 1a (AT1a) receptors are critical in the control of blood
      pressure and water balance. Experiments were performed to determine the influence
      of dehydration on brain Ang receptors and plasma vasopressin (VP) in mice lacking
      this receptor. Control or AT1a knockout (AT1aKO) male mice were give water ad
      libitum or deprived of water for 48 hours. Animals were anesthetized with
      halothane, blood samples were collected by heart puncture, and brains were
      processed for Ang-receptor autoradiography with 125I-sarthran (0.4 nmol/L).
      Dehydration produced an increase in AT1 receptors in the paraventricular nucleus
      (PVN) and anterior pituitary (AP) in control mice (PVN: 70+/-16 versus 146+/-10
      fmol/mg protein; AP: 41+/-7 versus 86+/-15 fmol/mg protein). No changes were
      noted in the median preoptic nucleus. The majority of the brain receptors were of
      the AT1 subtype. There was little or no specific Ang binding in AT1aKO mice and
      no effect of dehydration. Plasma VP levels were elevated in the halothane
      anesthetized animals (>200 pg/mL) with no significant effect of dehydration. A
      separate experiment was performed with decapitated mice anesthetized with
      pentobarbital. Dehydration increased plasma VP in control mice, from 3.3+/-0.6 to
      13.3+/-4.7 pg/mL, whereas no change was noted in the AT1aKO mice, 5.1+/-0.3
      versus 6.1+/-0.7 pg/mL (water versus dehydration). These results demonstrate a
      differential response to dehydration in mice lacking AT1a receptors. There was no
      evidence for AT1 receptors of any subtype in the brain regions examined and no
      effect of dehydration on VP secretion or brain Ang receptors.

PMID- 9931153
TI  - Renal nerves promote sodium excretion during long-term increases in salt intake.
AB  - To determine whether the renal nerves contribute to sodium homeostasis during
      long-term increments in sodium intake, studies were conducted in conscious dogs
      subjected to unilateral renal denervation and surgical division of the urinary
      bladder into hemibladders to allow separate 24-hour urine collection from
      denervated and innervated kidneys. They were fed a low sodium diet and
      continuously infused with isotonic saline (350 mL/d) to provide a daily sodium
      intake of approximately 60 mmol. After control measurements, sodium intake was
      increased to 470 mmol/d by increasing the rate of isotonic saline infusion to
      3000 mL/d for 5 days; this was followed by a 5-day recovery period. Twenty-four
      hour control values for mean arterial pressure and ratios for urinary sodium,
      potassium, and creatinine excretion from denervated and innervated kidneys
      (DEN/INN) were 96+/-3, 1.06+/-0.04, 1.00+/-0.04, and 1.01+/-0.02 mm Hg,
      respectively. During the approximately 8-fold increase in sodium intake, there
      was no long-term change in mean arterial pressure, and daily sodium balance was
      achieved within 48 hours. Moreover, during the first day of high salt intake,
      there were significant reductions in the DEN/INN for sodium and potassium
      excretion, which persisted for the entire 5-day period of increased sodium
      intake; on day 5, the DEN/INN for sodium and potassium excretion was 0.86+/-0.03
      and 0.86+/-0.04, respectively. In contrast, the DEN/INN for creatinine excretion
      remained at control levels during high salt intake. Furthermore, similar long
      term reductions in the DEN/INN for sodium and potassium excretion occurred in a
      second group of dogs administered adrenergic receptor-blocking agents for 5 days
      to interrupt the functional effects of the renal nerves. These data indicate that
      sustained renal sympathoinhibition promotes sodium and potassium excretion during
      long-term increments in sodium intake by inhibiting tubular reabsorption of these
      electrolytes.

PMID- 9931154
TI  - CGRP activates renal pelvic substance P receptors by retarding substance P
      metabolism.
AB  - Substance P and calcitonin gene-related peptide (CGRP) are colocalized in renal
      pelvic sensory nerves. Increasing renal pelvic pressure results in an increase in
      afferent renal nerve activity that is blocked by a substance P receptor
      antagonist but not by a CGRP receptor antagonist. CGRP potentiates the effects of
      substance P by preventing the metabolism of substance P. Therefore, we examined
      whether CGRP enhanced the afferent renal nerve activity responses to substance P
      and increased renal pelvic pressure, a stimulus known to increase substance P
      release. Combined administration of substance P and CGRP into the renal pelvis
      resulted in an increase in afferent renal nerve activity (1392+/-217%. s; area
      under the curve of afferent renal nerve activity versus time) that was greater
      (P<0.01) than that produced by substance P (620+/-156%. s) or CGRP (297+/-96%. s)
      alone. Likewise, CGRP enhanced the afferent renal nerve activity response to
      increased renal pelvic pressure. During renal pelvic administration of the
      neutral endopeptidase inhibitor thiorphan, the afferent renal nerve activity
      response to substance P plus CGRP was similar to that produced by either
      neuropeptide alone. Because these studies suggested that CGRP potentiated the
      afferent renal nerve activity responses to substance P, we examined whether the
      afferent renal nerve activity response to CGRP was blocked by a substance P
      receptor antagonist, RP67580. RP67580 blocked the afferent renal nerve activity
      response to CGRP by 85+/-12% (P<0.02). We conclude that CGRP activates renal
      pelvic sensory nerves by retarding the metabolism of substance P, thereby
      increasing the amount of substance P available for stimulation of substance P
      receptors.

PMID- 9931156
TI  - Selective inhibition of the renal dopamine subtype D1A receptor induces
      antinatriuresis in conscious rats.
AB  - Both dopamine D1-like (D1A and D1B) and D2-like (D2, D3, and D4) receptor
      subfamilies are present in the kidney. Blockade of the intrarenal D1-like
      receptor family is associated with natriuresis and diuresis. Because the D1A and
      D1B receptor subtypes are not distinguishable by currently available dopaminergic
      agents, their functional role remains undefined. In the present study, the effect
      of selective inhibition of the renal D1A receptor with phosphorothioated
      antisense oligodeoxynucleotide (AS-ODN) was investigated in conscious
      uninephrectomized rats. After renal interstitial administration of Texas red
      labeled D1A receptor AS-ODN, intense fluorescent signal was localized in the
      renal tubular epithelium and vasculature. In rats on normal salt intake, AS-ODN
      injected interstitially into the kidney reduced daily urinary sodium excretion
      (1.4+/-0.04 versus 0.8+/-0.2 mEq/d, n=5, P<0.05) and urine output (16.9+/-3.8
      versus 12.5+/-3.6 mL/d, n=5, P<0.05). In rats on high sodium intake, continuous
      renal interstitial administration of D1A receptor AS-ODN transiently decreased
      daily urinary sodium excretion (5.4+/-0.5 versus 4.2+/-0.3 mEq/d, n=7, P<0.01)
      and urine output (27.6+/-4.5 versus 18.1+/-1.8 mL/d, n=7, P<0.01). Neither
      vehicle nor sense oligodeoxynucleotide had significant effects. Systolic blood
      pressure remained unchanged. The renal D1A receptor protein was significantly
      decreased by 35% and 46% at the end of the study in AS-ODN-treated rats on normal
      and high salt intake, respectively, whereas the D1B receptor and beta-actin were
      not affected. These results provide the first direct evidence that the renal D1A
      receptor subtype plays an important role in the control of sodium excretion.

PMID- 9931155
TI  - Antihypertensive mechanisms underlying a novel salt-sensitive hypertensive model
      induced by sensory denervation.
AB  - A novel model of hypertension recently developed in our laboratory shows that
      neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat
      responsive to a salt load with a significant rise in blood pressure. To determine
      the role of the renin-angiotensin system and the sympathetic nervous system in
      the development of hypertension in this model, newborn Wistar rats were given
      capsaicin 50 mg/kg SC on the first and second days of life. Control rats were
      treated with vehicle. After they were weaned, male rats were divided into 6
      groups and subjected to the following treatments for 2 weeks: control+high sodium
      diet (4%) (CON-HS), capsaicin+normal sodium diet (0.5%) (CAP-NS), capsaicin+high
      sodium diet (CAP-HS), capsaicin+high sodium diet+losartan (10 mg/kg per day) (CAP
      HS-LO), capsaicin+high sodium diet+prazosin (3 mg/kg per day) (CAP-HS-PR), and
      capsaicin+high sodium diet+hydralazine (10 mg/kg per day) (CAP-HS-HY). Levels of
      calcitonin gene-related peptide in dorsal root ganglia were decreased by
      capsaicin treatment (P<0.05). Both tail-cuff systolic blood pressure and mean
      arterial pressure were higher in CAP-HS and CAP-HS-PR than in CON-HS, CAP-NS, CAP
      HS-LO, and CAP-HS-HY (P<0.05). The 24-hour urinary volume and sodium excretion
      were increased when a high sodium diet was given (P<0.05), but they were lower in
      CAP-HS, CAP-HS-LO, CAP-HS-PR, and CAP-HS-HY than in CON-HS (P<0.05). Urinary
      potassium excretion was not different among all 6 groups. We conclude that
      blockade of the angiotensin type 1 receptor with losartan but not antagonism of
      the alpha1-adrenoreceptor with prazosin prevents the development of salt
      sensitive hypertension induced by sensory denervation. Sensory denervation
      impairs urinary sodium and water excretion in response to a high sodium intake,
      regardless of blood pressure, suggesting that sensory innervation plays a direct
      role in regulating the natriuretic response to sodium loading.

PMID- 9931157
TI  - Effect of chronic salt loading on adenosine metabolism and receptor expression in
      renal cortex and medulla in rats.
AB  - Previous studies have shown that chronic salt loading increased renal
      interstitial adenosine concentrations and desensitized renal effects of
      adenosine, a phenomenon that could facilitate sodium excretion. However, the
      mechanisms responsible for the increased adenosine production and decreased
      adenosine response are poorly understood. This study examined the effects of the
      dietary high salt intake on adenosine metabolism and receptor expression in the
      renal cortex and medulla in Sprague Dawley rats. Fluorescent high-performance
      liquid chromatography analyses were performed to determine adenosine levels in
      snap-frozen kidney tissues. Comparing rats fed a normal (1% NaCl) versus high
      salt (4% NaCl) diet, renal adenosine concentrations in rats fed a high salt diet
      were significantly higher (cortex: 43+/-3 versus 85+/-4, P<0.05; medulla: 183+/-4
      versus 302+/-8 nmol/g wet tissue, P<0.05). Increased adenosine concentrations
      were not associated with changes in the 5'-nucleotidase or adenosine deaminase
      activity, as determined by quantitative isoelectric focusing and gel
      electrophoresis. Western blot analyses showed that a high salt diet (4% NaCl for
      3 weeks) downregulated A1 receptors (antinatriuretic type), did not alter A2A and
      A2B receptors (natriuretic type), and upregulated A3 receptors (function unknown)
      in both renal cortex and medulla. The data show that stimulation of adenosine
      production and downregulation of A1 receptors with salt loading may play an
      important role in adaptation in the kidney to promote sodium excretion.

PMID- 9931158
TI  - Handling 22NaCl by the blood-brain barrier and kidney: its relevance to salt
      induced hypertension in dahl rats.
AB  - We previously reported that inappropriate renal vasoconstriction in Dahl salt
      sensitive (DS) rats fed high NaCl diets may cause sodium retention. The present
      study examined the distribution and elimination of 22Na in DS and Dahl salt
      resistant (DR) rats, and we determined whether an abnormality in renal function
      might also cause sodium retention in DS rats. Following an intravenous bolus of 4
      microCi 22NaCl in prehypertensive DS and DR rats with similar blood pressures on
      low (0.23%) or high (8% for 4 days) NaCl diets, urinary clearance of 22Na in 1
      hour was about 4 times less in DS than DR rats, and renal retention of 22Na was
      up to 8 times greater in DS than DR rats (P<0.01), suggesting that a renal
      functional defect may contribute to salt retention in DS rats; however, its
      uptake in tail artery, heart, lungs, liver, and spleen was similar in DS and DR
      rats. Uptake in brain was up to 5 times greater in DS than DR rats (P<0.01).
      Cerebrospinal fluid 22Na radioactivity (in counts per minute) revealed that the
      blood-brain barrier is 5 to 8 times more permeable to sodium in DS than DR rats
      (P<0.01). Cerebrospinal fluid volume and brain water content increased
      significantly (P<0.01) in DS but not DR rats on an 8% NaCl diet.
      Intracerebroventricular bolus injection of 0.06 mL of 4.5 mol/L NaCl acutely and
      transiently induced the same degree of hypertension in DR and DS rats, whereas
      similar volume injections of isotonic saline, 4.5 mol/L Na-acetate, or 4.5 mol/L
      NaBr did not produce hypertension in either strain. We conclude that functional
      abnormalities in DS rat kidneys may cause retention of NaCl and that an increased
      blood-brain barrier permeability to NaCl may enhance its access to sites in the
      brain that are then activated and induce hypertension.

PMID- 9931159
TI  - Alpha1- and alpha2-adrenoceptor control of sodium transport reverses in
      developing hypertension.
AB  - Alpha-Adrenergic receptor (AR) activation enhances sodium retention in certain
      forms of hypertension. The objective of the present study was to understand the
      role of alpha-ARs in regulating sodium transport by distal tubules (DT). DT cells
      were isolated from kidneys of spontaneously hypertensive rats (SHR) and Wistar
      Kyoto (WKY) rats at 6 weeks, when hypertension is developing, or at 12 weeks,
      when hypertension is established. The alpha1-AR agonist phenylephrine increased
      22Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY
      cells. The alpha2-AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks,
      the pattern of alpha-AR regulation was reversed: alpha1-AR-induced sodium uptake
      was only 15%, whereas alpha2-AR activation increased sodium uptake by 35% in SHR
      and WKY cells. alpha1-AR-induced sodium uptake in 6-week SHR cells was abolished
      by prazosin; alpha2-AR-stimulated sodium uptake was blocked by yohimbine in 12
      week SHR and WKY. Competitive binding studies were performed with [3H]prazosin
      and alpha1A-, alpha1B-, and alpha1D-selective antagonists with DT cell membranes
      from 6- and 12-week SHR and WKY. alpha2-AR subtypes were determined with
      [3H]rauwolscine and alpha2A- and alpha2B-selective antagonists. Expression of
      alpha1B-ARs was increased 4-fold in DT cells during the developing phase of
      hypertension in SHR. No change was detected in alpha2-AR expression. DT cells
      transiently increase [Ca2+]i in response to alpha1-AR agonists from 6-week but
      not 12-week SHR. Conversely, alpha2-AR agonists increase [Ca2+]i at 12 weeks. In
      summary, during developing hypertension, alpha1-ARs increase sodium uptake and
      [Ca2+]i in SHR cells. Expression of alpha1B-ARs is selectively upregulated during
      developing hypertension. In established hypertension (and normotension), alpha2
      ARs regulate sodium transport and [Ca2+]i in DT cells. We conclude that a
      molecular switch of alpha1-AR and alpha2-AR signaling occurs in DT cells during
      the development of hypertension.

PMID- 9931160
TI  - Enhanced gamma-aminobutyric acid-B receptor agonist responses and mRNA within the
      nucleus of the solitary tract in hypertension.
AB  - Gamma-Aminobutyric acid-B (GABAB) receptor function and regulation in the nucleus
      of the solitary tract (NTS) was examined in Sprague-Dawley rats made chronically
      (4 to 5 weeks) hypertensive with the one-kidney, figure-8 renal wrap model of
      hypertension. NTS microinjection of the GABAB agonist baclofen produced a pressor
      response that was enhanced in hypertensive rats compared with the response
      observed in sham-operated normotensive rats (36+/-4 mm Hg increase in mean
      arterial pressure in 8 hypertensive rats compared with 21+/-2 mm Hg increase in 7
      sham-operated normotensive rats, P=0. 03). Responses to microinjection of GABAB
      antagonists (CGP-55845A and SCH-90511), the GABAA agonist muscimol, the GABAA
      antagonist bicuculline, and the GABA reuptake inhibitor nipecotic acid were not
      different comparing normotensive sham-operated and hypertensive rats. Renal
      sympathetic nerve responses to NTS microinjection of these drugs were not
      different in hypertensive compared with normotensive rats. Micropunches of the
      NTS were homogenized and reverse transcriptase-polymerase chain reaction was
      performed to examine mRNA levels for the GABAB receptor. There was a 3-fold
      increase in GABAB receptor mRNA levels in the caudal NTS of 7 chronically
      hypertensive rats compared with levels measured in 8 sham-operated normotensive
      rats (P=0.01). In conclusion, chronic hypertension is associated with an
      upregulation of GABAB receptor function; however, the tonic activity of the
      system does not appear to be different between normotensive and hypertensive
      rats. The upregulation of GABAB receptor function might be due to an increased
      number of receptors, as suggested by the elevated levels of GABAB receptor mRNA
      measured in the NTS of hypertensive rats. All of these alterations suggest that
      hypertension is associated with dynamic changes in receptor-mediated mechanisms
      within the NTS, and these alterations could modify baroreflex regulation of
      cardiovascular function in hypertension.

PMID- 9931161
TI  - State-of-the-art-lecture: Obesity-induced hypertension: new concepts from the
      emerging biology of obesity.
AB  - offsity is associated with an increased risk of hypertension. In the past 5 years
      there have been dramatic advances into the genetic and neurobiological mechanisms
      of obesity with the discovery of leptin and novel neuropeptide pathways
      regulating appetite and metabolism. In this brief review, we argue that these
      mounting advances into the neurobiology of obesity have and will continue to
      provide new insights into the regulation of arterial pressure in obesity. We
      focus our comments on the sympathetic, vascular, and renal mechanisms of leptin
      and melanocortin receptor agonists and on the regulation of arterial pressure in
      rodent models of genetic obesity. We suggest 3 concepts. First, the effect of
      obesity on blood pressure may depend critically on the genetic-neurobiological
      mechanisms underlying the obesity. Second, obesity is not consistently associated
      with increased blood pressure, at least in rodent models. Third, the blood
      pressure response to obesity may be critically influenced by modifying alleles in
      the genetic background.

PMID- 9931162
TI  - Interactions between the melanocortin system and leptin in control of sympathetic
      nerve traffic.
AB  - Leptin plays an important role in regulation of body weight through regulation of
      food intake and sympathetically mediated thermogenesis. The hypothalamic
      melanocortin system, via activation of the melanocortin-4 receptor (MC4-R),
      decreases appetite and weight, but its effects on sympathetic nerve activity
      (SNA) are unknown. In addition, it is not known whether sympathoactivation to
      leptin is mediated by the melanocortin system. We tested the interactions between
      these systems in regulation of brown adipose tissue (BAT) and renal and lumbar
      SNA in anesthetized Sprague-Dawley rats. Intracerebroventricular administration
      of the MC4-R agonist MT-II (200 to 600 pmol) produced a dose-dependent
      sympathoexcitation affecting BAT and renal and lumbar beds. This response was
      completely blocked by the MC4-R antagonist SHU9119 (30 pmol ICV). Administration
      of leptin (1000 microg/kg IV) slowly increased BAT SNA (baseline, 41+/-6
      spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001) and renal SNA (baseline, 116+/-16
      spikes/s; 6 hours, 169+/-26 spikes/s; P=0.014). Intracerebroventricular
      administration of SHU9119 did not inhibit leptin-induced BAT sympathoexcitation
      (baseline, 35+/-7 spikes/s; 6 hours, 158+/-34 spikes/s; P=0.71 versus leptin
      alone). However, renal sympathoexcitation to leptin was completely blocked by
      SHU9119 (baseline, 142+/-17 spikes/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus
      leptin alone). This study demonstrates that the hypothalamic melanocortin system
      can act to increase sympathetic nerve traffic to thermogenic BAT and other
      tissues. Our data also suggest that leptin increases renal SNA through activation
      of hypothalamic melanocortin receptors. In contrast, sympathoactivation to
      thermogenic BAT by leptin appears to be independent of the melanocortin system.

PMID- 9931163
TI  - Clonidine prevents insulin resistance and hypertension in obese dogs.
AB  - The role that the central sympathetic nervous system plays in the development of
      obesity hypertension and insulin was evaluated by feeding dogs a high fat diet
      with or without clonidine treatment. Thirteen adult mongrel dogs were chronically
      instrumented and randomly assigned to receive either a high fat diet and no
      clonidine (n=6) or a high fat diet plus clonidine (n=7), 0.3 mg BID. Blood
      pressure, heart rate, plasma insulin, and electrolytes were measured daily.
      Insulin resistance was assessed with a multiple-dose euglycemic clamp (1, 2, and
      30 mU. kg-1. min-1) before and after 1, 3, and 6 weeks of the high fat diet.
      Clonidine prevented the hypertension, tachycardia, and insulin resistance
      associated with feeding dogs the high fat diet but did not affect weight gain.
      The present study suggests that the central sympathetic nervous system plays a
      critical role in the development of both insulin resistance and hypertension
      associated with feeding dogs a high fat diet.

PMID- 9931164
TI  - Insulin-mediated vasodilation and glucose uptake are functionally linked in
      humans.
AB  - Intra-arterial infusion of insulin in physiological doses causes forearm
      vasodilation which is augmented by co-infusion of D-glucose, leading us to
      speculate that local insulin-mediated vasodilation may depend on insulin-mediated
      glucose uptake. We have examined the relationship between whole-body insulin
      sensitivity and forearm vasodilation in response to local infusion of
      insulin/glucose, thus avoiding any confounding effects of sympathetic stimulation
      on peripheral blood flow. Eighteen healthy, normotensive male volunteers (age,
      26+/-5.4 years) attended on two separate occasions for measurement of: (1) whole
      body insulin sensitivity with use of the hyperinsulinemic euglycemic clamp; (2)
      forearm vasodilation in response to an intra-arterial infusion of insulin/glucose
      with use of bilateral venous occlusion plethysmography. Insulin-mediated glucose
      uptake (M) for the group (mean+/-SD) was 10.0+/-2.2 mg. kg-1. min-1, and the
      percentage change in forearm blood flow ratio (%FBFR) for the group (median,
      interquartile range) was 28.2% (13.6, 48.6). In univariate analysis, M was
      significantly correlated with %FBFR (rs=0.60, P<0.05), but not with body mass
      index (BMI) (rs=-0. 42), age (r=-0.39) or mean arterial pressure (r=0.13). In
      multiple regression analysis, %FBFR remained a significant independent predictor
      of M (R2 (adj)=0.48, t=3.23, P<0.01) in a model involving BMI, age, and blood
      pressure. These data support the concept of a significant functional relationship
      between insulin's metabolic and vascular actions, possibly at an endothelial
      level.

PMID- 9931166
TI  - Postprandial hypotension is associated with asymptomatic cerebrovascular damage
      in essential hypertensive patients.
AB  - offelucidate the relationship between postprandial hypotension (PPH) and
      asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after
      a meal by 24-hour blood pressure monitoring in 70 hospitalized essential
      hypertensive patients aged >/=50 years. They received a diet containing standard
      nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication
      for at least 1 week. PPH was defined as the mean reduction of systolic blood
      pressure during 2 hours after a meal. Patients were divided into three groups
      according to mean values of PPH after 3 meals: PPH-1 (n=16, 5 mm Hg</=PPH<10 mm
      Hg), PPH-2 (n=18, PPH>/=10 mm Hg), and normal (n=36, PPH<5 mm Hg). As
      asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by
      magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood
      pressure or the nondipper phenomenon; however, PPH was significantly related to
      asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH
      1, and PPH-2 groups was 44%, 69%, and 83%, respectively (chi2=8.22, P<0.05). The
      number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0+/-1.3, 1.3+/
      1.2, and 1. 9+/-1.4, respectively (F[2,67]=3.2, P<0.05). The prevalence of
      advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and
      83%, respectively (chi2=7.63, P<0.05). Severity score of leukoaraiosis in the
      normal, PPH-1, and PPH-2 groups was 1.5+/-0. 7, 1.7+/-0.8, and 2.1+/-0.7,
      respectively (F[2,67]=4.3, P<0.05). These findings indicate that elderly
      hypertensive patients with marked PPH should be considered to have advanced
      cerebrovascular damage even in the absence of abnormal neurological findings.

PMID- 9931167
TI  - Mechanics and composition of human subcutaneous resistance arteries in essential
      hypertension.
AB  - Mechanical properties of arteries are altered in some rat models of hypertension,
      and this may influence peripheral resistance and blood pressure as well as some
      of the complications of hypertension. It has usually been assumed that arterial
      wall stiffness is increased in hypertension, although recent studies suggest that
      this may not necessarily be the case in large arteries. We determined whether the
      mechanics of human resistance arteries are altered in hypertension. Subcutaneous
      resistance arteries (lumen diameter<300 microm) were isolated from hypertensive
      and normotensive subjects of similar ages (46+/-3 and 43+/-4 years,
      respectively). Vessels were mounted in a pressurized myograph, deactivated, and
      exposed to intraluminal pressures ranging from 3 to 140 mm Hg. At each pressure,
      lumen and media dimensions were measured. Media-to-lumen ratio and media width
      were greater in hypertensive vessels, reducing wall stress (P<0.01), whereas
      media cross section was similar in vessels from both groups. Isobaric elastic
      modulus (which is influenced by vessel geometry and by wall component stiffness)
      was lower in hypertensive vessels (P<0. 01). Stiffness of wall components (slope
      of incremental elastic modulus versus stress, which is geometry-independent) was
      significantly lower in hypertensive vessels (8.2+/-0.7) versus normotensive
      vessels (11.0+/-1.0, P<0.05), whereas distensibility was unchanged. Electron
      microscopic analysis of the media of the small arteries showed a greater collagen
      to elastin ratio (P<0.05) in the media of vessels from hypertensive patients. In
      conclusion, the stiffness of wall components (slope of elastic modulus versus
      stress) is not increased but is in fact decreased in subcutaneous resistance
      arteries from patients with mild essential hypertension. Reduced stiffness of
      resistance arteries from hypertensive patients does not appear to relate to
      changes in volume density of extracellular matrix components but may be the
      result of changes in extracellular matrix architecture or cell-matrix attachment,
      which remains to be established.

PMID- 9931165
TI  - Hyperglycemia and angiotensin-mediated control of the renal circulation in
      healthy humans.
AB  - Type 1 and type 2 diabetics have an enhanced renal vasodilator response to
      angiotensin-converting enzyme (ACE) inhibition despite suppressed plasma renin
      activity (PRA), indicating possible activation of the intrarenal renin
      angiotensin system. To investigate the role of hyperglycemia, we evaluated the
      renal hemodynamic response to ACE inhibition in 9 healthy subjects in high-salt
      balance after steady-state hyperglycemia (8.4+/-1 mmol/L) was achieved via
      intravenous glucose administration. Renal plasma flow (RPF) and glomerular
      filtration rate (GFR) responses to captopril and to angiotensin II (Ang II) were
      measured as paraminohippuric acid and inulin clearances. Hyperglycemia produced a
      significant increase in RPF of 117 mL. min-1. 1.73 m-2 after 90 minutes but not
      GFR. Administration of captopril at a dose of 25 mg during glucose infusion led
      to an increase in RPF of 173+/-24 mL. min-1. 1.73 m-2 (P<0.01) but did not
      significantly change RPF in the absence of hyperglycemia (7+/-21 mL. min-1. 1.73
      m-2). Captopril did not alter GFR in the presence or absence of hyperglycemia.
      Ang II infusion during hyperglycemia decreased RPF by 45+/-16 mL. min-1. 1. 73 m
      2, and this was significantly enhanced by captopril (-98+/-26 mL. min-1. 1.73 m
      2, P<0.05). In contrast, there was no enhancement of the vasoconstrictor response
      to Ang II in the absence of hyperglycemia. PRA did not change with hyperglycemia.
      Enhancement of renal vasodilation during hyperglycemia by captopril without
      alteration of PRA suggests activation of the intrarenal renin angiotensin system.

PMID- 9931168
TI  - Effect of treatment on flow-dependent vasodilation of the brachial artery in
      essential hypertension.
AB  - off aim of our study was to evaluate the effect of antihypertensive treatment on
      flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of
      endothelial function, in hypertensive patients. In 78 consecutive hypertensive
      patients (40%men; age range, 42 to 67 years) we measured by a high-resolution
      ultrasound system the changes of brachial artery diameter during reactive
      hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery
      flow velocity was measured by pulsed Doppler. The results of 2 studies are
      reported. In the first study, this procedure was repeated in 58 patients after 6
      and 12 months of treatment with a combination of antihypertensive drugs; in a
      second study, the FMD was assessed in 20 patients after 2 months of monotherapy
      with either nifedipine or hydrochlorothiazide. In the first study, FMD was
      significantly increased after treatment compared with baseline (from 3.1+/-3% at
      baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by
      ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg
      to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA);
      significant changes of endothelium-independent dilation were also observed, but
      only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6
      months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD
      was significantly increased during nifedipine treatment as compared with baseline
      (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change
      in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to
      4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation
      were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from
      18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide,
      respectively, NS). Thus, in essential hypertensive patients an improvement of the
      impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be
      observed after long-term, effective blood pressure reduction, suggesting a
      beneficial effect of antihypertensive treatment on endothelial function. It seems
      that beyond blood pressure control, a calcium antagonist may be more effective
      than a diuretic in this respect.

PMID- 9931169
TI  - Systemic blockade of the endothelin-B receptor increases peripheral vascular
      resistance in healthy men.
AB  - Endothelin-1 (ET-1) is an important mediator of vascular tone in humans, and a
      number of endothelin receptor antagonists are currently in clinical development
      as vasodilator agents. While the vasoconstrictor role of the ETA receptor is
      undisputed, the role of the ETB receptor remains unclear. Hemodynamic effects of
      systemic doses of the ETB-selective antagonist BQ-788 were investigated in 5
      healthy male volunteers (age range, 33 to 48 years) in a placebo-controlled, four
      way crossover study. After a 15-minute infusion of BQ-788 (3, 30, or 300
      nmol/min) or placebo, plasma ET-1 and big ET-1, blood pressure, heart rate,
      cardiac index, and stroke index were measured. Total peripheral vascular
      resistance was calculated from cardiac index and mean arterial pressure.
      Hemodynamic data are expressed as maximum, placebo-corrected, percentage change
      from baseline following BQ-788 (300 nmol/min) and were examined by ANOVA. Plasma
      ET-1 increased by 3.7+/-1.2 pg/mL (maximum at 15 minutes, P=0.02), whereas there
      was no significant change in plasma big ET-1. Although BQ-788 had no effect on
      mean arterial pressure, there was a reduction in heart rate (13+/-7% at 50
      minutes; P=0.002), cardiac index (17+/-5% at 40 minutes; P<0. 0001), and stroke
      index (8+/-4% at 40 minutes; P=0.002) and an increase in total peripheral
      vascular resistance (24+/-5% at 40 minutes; P<0.0001). The selective ETB receptor
      antagonist BQ-788 causes peripheral vasoconstriction in healthy volunteers,
      suggesting that the overall balance of effects of endogenous ET-1 at the vascular
      ETB receptor favors vasodilatation. Further investigation is now clearly required
      to address whether selective ETA or combined ETA/ETB receptor blockade will be
      more effective in the clinical setting.

PMID- 9931170
TI  - Effects of smoking cessation on blood pressure and heart rate variability in
      habitual smokers.
AB  - We investigated the effects of 1-week of smoking cessation on ambulatory blood
      pressure, heart rate, and heart rate variability in 39 normotensive male habitual
      smokers (mean+/-SEM, 32.5+/-1.0 years). The ambulatory blood pressure, heart
      rate, and ECG R-R intervals were measured during a 24-hour period with a portable
      recorder (TM-2425) on the last day of 1-week smoking and nonsmoking periods. The
      order of the 2 periods was randomized. In the smoking period, the subjects were
      instructed to smoke cigarettes according to their usual smoking patterns. A power
      spectral analysis of R-R intervals was performed to obtain the low-frequency (LF)
      and high-frequency (HF) components. The percentage of differences between
      adjacent normal R-R intervals >50 milliseconds (pNN50) was used as a time-domain
      measure of heart rate variability. The 24-hour ambulatory blood pressure was
      significantly lower in the nonsmoking period than in the smoking period, by 3.5+/
      1.1 mm Hg systole [P<0. 01] and by 1.9+/-0.7 mm Hg diastole [P<0.05], whereas the
      nighttime blood pressure did not differ significantly between the 2 periods. The
      24-hour heart rate was significantly lower in the nonsmoking period than in the
      smoking period, by 7.3+/-1.0 beats/min (P<0.0001). The pNN50 and the 24-hour HF
      component were significantly higher in the nonsmoking period than in the smoking
      period (P<0.0001 for each). The plasma norepinephrine and epinephrine
      concentrations were significantly lower in the nonsmoking period than in the
      smoking period (P<0.05 for each). These results demonstrate the substantial and
      immediate benefits of smoking cessation on these cardiovascular indices.

PMID- 9931172
TI  - Merck new investigator award 1998 

PMID- 9931171
TI  - Daily aerobic exercise improves reactive hyperemia in patients with essential
      hypertension.
AB  - The effects of long-term aerobic exercise on endothelial function in patients
      with essential hypertension remain unclear. To determine whether endothelial
      function relating to forearm hemodynamics in these patients differs from
      normotensive subjects and whether endothelial function can be modified by
      continued physical exercise, we randomized patients with essential hypertension
      into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for
      12 weeks (n=20) or a group that underwent no activity modifications (control
      group, n=7). Forearm blood flow was measured using strain-gauge plethysmography
      during reactive hyperemia to test for endothelium-dependent vasodilation and
      after sublingual nitroglycerin administration to test endothelium-independent
      vasodilation. Forearm blood flow in hypertensive patients during reactive
      hyperemia was significantly less than that in normotensive subjects (n=17).
      Increases in forearm blood flow after nitroglycerin were similar between
      hypertensive and normotensive subjects. Exercise lowered mean blood pressure from
      115.7+/-5.3 to 110.2+/-5.1 mm Hg (P<0.01) and forearm vascular resistance from
      25.6+/-3.2 to 23. 2+/-2.8 mm Hg/mL per minute per 100 mL tissue (P<0.01); no
      change occurred in controls. Basal forearm blood flow, body weight, and heart
      rate did not differ with exercise. After 12 weeks of exercise, maximal forearm
      blood flow response during reactive hyperemia increased significantly, from
      38.4+/-4.6 to 47.1+/-4.9 mL/min per 100 mL tissue (P<0.05); this increase was not
      seen in controls. Changes in forearm blood flow after sublingual nitroglycerin
      administration were similar before and after 12 weeks of exercise. Intra-arterial
      infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine
      abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise.
      These findings suggest that through increased release of nitric oxide, continued
      physical exercise alleviates impairment of reactive hyperemia in patients with
      essential hypertension.

PMID- 9931173
TI  - "Vasomotor responses of soleus feed arteries from sedentary and exercise-trained
      rats".

PMID- 9931174
TI  - Vasomotor responses of soleus feed arteries from sedentary and exercise-trained
      rats.
AB  - Our goals were to determine the nature of endothelium-dependent and -independent
      vascular responses in isolated soleus feed arteries (SFA) and to test the
      hypothesis that these responses would be altered by exercise training. Exercise
      trained rats ran 30 m/min, up a 15% grade, 1 h/day, 5 days/wk for 10-12 wk, while
      sedentary control rats were confined to normal cage activity. SFA were isolated,
      cannulated, and pressurized at 90 cmH2O. After a 1-h equilibration period, the
      dose-response relationships to constrictors, endothelium-dependent dilators, and
      endothelium-independent dilators were examined. SFA developed spontaneous tone,
      demonstrated myogenic reactivity by maintaining vessel diameter in the face of
      large changes in intraluminal pressure, and constricted in a dose-dependent
      manner to norepinephrine and potassium chloride. SFA dilated in a dose-dependent
      manner to the endothelium-dependent dilators acetylcholine and increased flow and
      to the endothelium-independent dilator sodium nitroprusside. SFA did not dilate
      to the putative endothelium-dependent dilators bradykinin, substance P, and
      clonidine or to adenosine. Dilation to acetylcholine was attenuated markedly by
      arginine analogs and less by 20 mM KCl, but it was unaltered by indomethacin.
      These results indicate that SFA respond to a number of vasoactive substances,
      consistent with the hypothesis that SFA participate in the control of vascular
      resistance. However, exercise training does not appear to elicit a stimulus
      adequate to alter vasomotor responses in SFA.

PMID- 9931175
TI  - Effect of short-term training on mitochondrial ATP production rate in human
      skeletal muscle.
AB  - Seven untrained volunteers [3 men, 4 women, 20.1 +/- 2.0 (SD) yr, 66. 0 +/- 11.0
      kg, 171 +/- 13 cm] participated in a 10-day cycle exercise training program.
      Resting muscle samples were obtained from vastus lateralis before and after 5 and
      10 days of training. Mitochondrial ATP production rate (MAPR) was assayed in
      isolated mitochondria by using a bioluminescence technique and referenced to the
      activity of glutamate dehydrogenase in the muscle sample. MAPR increased 136 and
      161% after 10 days of training for the mitochondrial substrate combinations
      pyruvate + palmitoyl-L-carnitine + alpha-ketoglutarate + malate and palmitoyl-L
      carnitine + malate, respectively. Total muscle glutamate dehydrogenase and
      citrate synthase activity increased 53 and 16%, respectively, after 5 days but
      did not significantly increase further after 10 days. The results from the
      present study indicate that MAPR, measured by using the substrate combinations
      pyruvate + palmitoyl-L-carnitine + alpha-ketoglutarate + malate and palmitoyl-L
      carnitine + malate, can rapidly increase in response to endurance training.

PMID- 9931176
TI  - Bed rest increases the amount of mismatched fibers in human skeletal muscle.
AB  - The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expression
      on both mRNA and protein level in human skeletal muscle fibers were studied.
      Muscle biopsies from vastus lateralis muscle were obtained from seven healthy
      young male subjects before and after the bed-rest period. Combined in situ
      hybridization, immunocytochemistry, and ATPase histochemistry analysis of serial
      sections of the muscle biopsies demonstrated that fibers showing a mismatch
      between MHC isoforms at the mRNA and protein level increased significantly after
      the bed-rest period, suggesting an increase in the amount of muscle fibers in a
      transitional state. Accordingly, fibers showing a match in expression of MHC-1
      and of MHC-2A at the mRNA and protein level decreased, whereas fibers showing a
      match between MHC-2X mRNA and protein increased after bed rest. Overall, there
      was an increase in fibers in a transitional state from phenotypic type 1 --> 2A
      and 2A --> 2X. Furthermore, a number of fibers with unusual MHC mRNA and
      isoprotein combinations were observed after bed rest (e.g., type 1 fibers with
      only mRNA for 2X and type 1 fibers negative for mRNA for MHC-beta/slow, 2A, and
      2X). In contrast, no changes were revealed after an examination at the protein
      level alone. These data suggest that the reduced load-bearing activity imposed on
      the skeletal muscles through bed rest will alter MHC gene expression, resulting
      in combinations of mRNA and MHC isoforms normally not (or only rarely) observed
      in muscles subjected to load-bearing activity. On the other hand, the present
      data also show that 37 days of bed rest are not a sufficient stimulus to induce a
      similar change at the protein level, as was observed at the gene level.

PMID- 9931177
TI  - Effects of eccentric exercise on the immune system in men.
AB  - The effects of eccentric exercise on changes in numbers of circulating
      leukocytes, cell activation, cell adhesion, and cellular memory function were
      investigated in 12 men, aged 22-35 yr. The immunologic effects of postexercise
      epidermal treatment with monochromatic, infrared light were also evaluated. Blood
      was drawn before and 6, 24, and 48 h after exercise for phenotyping and analysis
      of creatine kinase activity. There was an increase in leukocyte, monocyte, and
      neutrophil number, no change in the number of basophils, eosinophils, B cells,
      and T cells, and a decrease in natural killer cell number postexercise. Some
      markers of lymphocyte and monocyte activation remained unchanged or decreased,
      whereas the expression of adhesion molecules 62L and 11b increased on monocytes.
      It is concluded that eccentric exercise induced decreased activation, and
      increased cell adhesion capacity, of monocytes. Altered trafficking of cells
      between lymphoid tissue and blood, selective apoptosis, or attachment/detachment
      from the endothelial wall can explain the observed phenotypic changes. Treatment
      with monochromatic, infrared light did not significantly affect any of the
      investigated variables. Correlations between immunologic and physiological
      parameters indicate a role of the immune system in adaptation to physical
      exercise.

PMID- 9931178
TI  - Endogenous vasopressin does not mediate hypoxia-induced anapyrexia in rats.
AB  - The present study was designed to test the hypothesis that arginine vasopressin
      (AVP) mediates hypoxia-induced anapyrexia. The rectal temperature of awake,
      unrestrained rats was measured before and after hypoxic hypoxia, AVP-blocker
      injection, or a combination of the two. Control animals received saline
      injections of the same volume. Basal body temperature was 36.52 +/- 0.29
      degreesC. We observed a significant (P < 0.05) reduction in body temperature of
      1. 45 +/- 0.33 degreesC after hypoxia (7% inspired O2), whereas systemic and
      central injections of AVP V1- and AVP V2-receptor blockers caused no change in
      body temperature. When intravenous injection of AVP blockers was combined with
      hypoxia, we observed a reduction in body temperature of 1.49 +/- 0.41 degreesC
      (V1-receptor blocker) and of 1.30 +/- 0.13 degreesC (V2-receptor blocker),
      similar to that obtained by application of hypoxia only. Similar results were
      observed when the blockers were injected intracerebroventricularly. The data
      indicate that endogenous AVP does not mediate hypoxia-induced anapyrexia in rats.

PMID- 9931179
TI  - Muscle glycogen accumulation after a marathon: roles of fiber type and pro- and
      macroglycogen.
AB  - Muscle glycogen remains subnormal several days after muscle damaging exercise.
      The aims of this study were to investigate how muscle acid-soluble macroglycogen
      (MG) and acid-insoluble proglycogen (PG) pools are restored after a competitive
      marathon and also to determine whether glycogen accumulates differently in the
      various muscle fiber types. Six well-trained marathon runners participated in the
      study, and muscle biopsies were obtained from the vastus lateralis of the
      quadriceps muscle before, immediately after, and 1, 2, and 7 days (days 1, 2, and
      7, respectively) after the marathon. During the race, 56 +/- 3.8% of muscle
      glycogen was utilized, and a greater fraction of MG (72 +/- 3.7%) was utilized
      compared with PG (34 +/- 6.5%). On day 2, muscle glycogen and MG values remained
      lower than prerace values, despite a carbohydrate-rich diet, but they had both
      returned to prerace levels on day 7. The PG concentration was lower on day 1
      compared with before the race, whereas there were no significant differences
      between the prerace PG concentration and the concentrations on days 2 and 7. On
      day 2 the glycogen concentration was particularly low in the type I fibers,
      indicating that local processes are important for the accumulation pattern. We
      conclude that a greater fraction of human muscle MG than of PG is utilized during
      a marathon and that accumulation of MG is particularly delayed after the
      prolonged exercise bout. Furthermore, factors produced locally appear important
      for the glycogen accumulation pattern.

PMID- 9931180
TI  - Respiratory gas-exchange ratios during graded exercise in fed and fasted trained
      and untrained men.
AB  - We evaluated the hypotheses that endurance training increases relative lipid
      oxidation over a wide range of relative exercise intensities in fed and fasted
      states and that carbohydrate nutrition causes carbohydrate-derived fuels to
      predominate as energy sources during exercise. Pulmonary respiratory gas-exchange
      ratios [(RER) = CO2 production/O2 consumption (VO2)] were determined during four
      relative, graded exercise intensities in both fed and fasted states. Seven
      untrained (UT) men and seven category 2 and 3 US Cycling Federation cyclists (T)
      exercised in the morning in random order, with target power outputs of 20 and 40%
      peak VO2 (VO2 peak) for 2 h, 60% VO2 peak for 1.5 h, and 80% VO2 peak for a
      minimum of 30 min after either a 12-h overnight fast or 3 h after a standardized
      breakfast. Actual metabolic responses were 22 +/- 0.33, 40 +/- 0.31, 59 +/- 0.32,
      and 75 +/- 0.39% VO2 peak. T subjects showed significantly (P < 0.05) decreased
      RER compared with UT subjects at absolute workloads when fed and fasted. Fasting
      significantly decreased RER values compared with the fed state at 22, 40, and 59%
      VO2 peak in T and at 40 and 59% VO2 peak in UT subjects. Training decreased (P <
      0.05) mean RER values compared with UT subjects at 22% VO2 peak when they fasted,
      and at 40% VO2 peak when fed or fasted, but not at higher relative exercise
      intensities in either nutritional state. Our results support the hypothesis that
      endurance training enhances lipid oxidation in men after a 12-h overnight fast at
      low relative exercise intensities (22 and 40% VO2 peak). However, a training
      effect on RER was not apparent at high relative exercise intensities (59 and 75%
      VO2 peak). Because most athletes train and compete at exercise intensities >40%
      maximal VO2, they will not oxidize a greater proportion of lipids compared with
      untrained subjects, regardless of nutritional state.

PMID- 9931181
TI  - Effects of load and tone on the mechanics of isolated human bronchial smooth
      muscle.
AB  - Isotonic and isometric properties of nine human bronchial smooth muscles were
      studied under various loading and tone conditions. Freshly dissected bronchial
      strips were electrically stimulated successively at baseline, after
      precontraction with 10(-7) M methacholine (MCh), and after relaxation with 10(-5)
      M albuterol (Alb). Resting tension, i.e., preload determining optimal initial
      length (Lo) at baseline, was held constant. Compared with baseline, MCh decreased
      muscle length to 93 +/- 1% Lo (P < 0.001) before any electrical stimulation,
      whereas Alb increased it to 111 +/- 3% Lo (P < 0.01). MCh significantly decreased
      maximum unloaded shortening velocity (0.045 +/- 0.007 vs. 0.059 +/- 0.007 Lo/s),
      maximal extent of muscle shortening (8.4 +/- 1.2 vs. 13.9 +/- 2.4% Lo), and peak
      isometric tension (6.1 +/- 0.8 vs. 7.2 +/- 1.0 mN/mm2). Alb restored all these
      contractile indexes to baseline values. These findings suggest that MCh
      reversibly increased the number of active actomyosin cross bridges under resting
      conditions, limiting further muscle shortening and active tension development.
      After the electrically induced contraction, muscles showed a transient phase of
      decrease in tension below preload. This decrease in tension was unaffected by
      afterload levels but was significantly increased by MCh and reduced by Alb. These
      findings suggest that the cross bridges activated before, but not during, the
      electrically elicited contraction may modulate the phase of decrease in tension
      below preload, reflecting the active part of resting tension.

PMID- 9931182
TI  - Mechanical properties of lung parenchyma during bronchoconstriction.
AB  - Interdependence between airways and the lung parenchyma is thought to be a major
      mechanism preventing excessive airway narrowing during bronchoconstriction.
      Because the elastance of the lung increases during bronchoconstriction, the
      lung's tethering force could also increase, further attenuating
      bronchoconstriction. We hypothesized that the bulk (kappa) and shear moduli (mu)
      of the lung increase similarly during bronchoconstriction. To test this
      hypothesis, we excised rabbit lungs and measured the lung volume, pulmonary
      elastance, kappa, and mu at transpulmonary pressures of 4, 6, 8, 12, and 16 cmH2O
      using pressure-volume curves, slow oscillations of the lung, and an indentation
      test. Bronchoconstriction was induced by nebulizing carbachol by using small
      tidal-volume ventilation to prevent hyperinflation. The measurement of kappa and
      mu was repeated after carbachol treatment. After carbachol treatment, the
      increase in kappa was significantly greater than that in mu. The estimated value
      for mu was approximately 0.5 x transpulmonary pressure both before and after
      carbachol treatment. These data suggest that the tethering effect of the lung
      parenchyma, which serves to attenuate bronchoconstriction, is not significantly
      increased during carbachol administration unless there is hyperinflation.

PMID- 9931183
TI  - Radiographic evidence of interstitial pulmonary edema after exercise at altitude.
AB  - Pulmonary function abnormalities after exercise are suggestive of pulmonary
      edema; however, radiographic evidence is lacking. Well-trained cyclists were
      studied to determine whether there is radiographic evidence of pulmonary edema
      after endurance exercise (cycling distance 5.3-131.5 km) at altitude. Chest
      radiographs obtained before exercise were coded for later interpretation. Films
      obtained after exercise were coded with a different number. A total of 74 sets of
      posteroanterior and lateral films were analyzed by three radiologists for signs
      of pulmonary edema. Radiographic changes were graded on a three-point scale. An
      edema score was calculated by summing the score for each individual radiographic
      finding for each radiologist and an overall edema score representing the mean
      scores from all three radiologists. The overall edema score increased from 0.8 +/
      1.2 before exercise to 1.8 +/- 1.6 after exercise (P < 0.01). These results
      suggest that, after prolonged high-intensity exercise at moderate altitude, there
      is radiographic evidence of early pulmonary edema in some cyclists.

PMID- 9931185
TI  - Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic
      effects in humans.
AB  - To evaluate whether interferon-gamma (IFN-gamma) is involved in the interaction
      between the immune and endocrine systems in vivo, we studied six healthy subjects
      twice in a placebo-controlled trial: once after administration of recombinant
      human IFN-gamma and, on another occasion, after administration of saline. The
      rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose and
      resting energy expenditure by indirect calorimetry. Human leukocyte antigen-DR
      gene expression on monocytes and serum neopterin increased after administration
      of IFN-gamma (P < 0.05 vs. control). IFN-gamma increased serum interleukin-6
      levels significantly. Levels of tumor necrosis factor-alpha remained below
      detection limits. IFN-gamma increased plasma concentrations of ACTH and cortisol
      (P < 0.05 vs. control), IFN-gamma did not alter concentrations of growth hormone,
      (nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth factor I.
      IFN-gamma did not alter plasma concentrations of glucose and free fatty acids nor
      the rate of appearance of glucose. IFN-gamma increased resting energy expenditure
      significantly. We conclude that IFN-gamma is a minor stimulator of the endocrine
      and metabolic pathways. Therefore, IFN-gamma by itself is probably not a major
      mediator in the interaction between the immune and the endocrine and metabolic
      systems.

PMID- 9931186
TI  - Soft palate muscle responses to negative upper airway pressure.
AB  - The afferent pathways and upper airway receptor locations involved in negative
      upper airway pressure (NUAP) augmentation of soft palate muscle activity have not
      been defined. We studied the electromyographic (EMG) response to NUAP for the
      palatinus, tensor veli palatini, and levator veli palatini muscles in 11 adult,
      supine, tracheostomized, anesthetized dogs. NUAP was applied to the nasal or
      laryngeal end of the isolated upper airway in six dogs and to four to six serial
      upper airway sites from the nasal cavity to the subglottis in five dogs. When
      NUAP was applied at the larynx, peak inspiratory EMG activity for the palatinus
      and tensor increased significantly (P < 0.05) and plateaued at a NUAP of -10
      cmH2O. Laryngeal NUAP failed to increase levator activity consistently. Nasal
      NUAP did not increase EMG activity for any muscle. Consistent NUAP reflex
      recruitment of soft palate muscle activity only occurred when the larynx was
      exposed to the stimulus and, furthermore, was abolished by bilateral section of
      the internal branches of the superior laryngeal nerves. We conclude that soft
      palate muscle activity may be selectively modulated by afferent activity
      originating in the laryngeal and hypopharyngeal airway.

PMID- 9931184
TI  - NO-cGMP pathway accentuates the decrease in heart rate caused by cardiac vagal
      nerve stimulation.
AB  - The role of the cardiac muscarinic-receptor-coupled nitric oxide (NO) pathway in
      the cholinergic control of heart rate (HR) is controversial. We investigated
      whether adding excessive NO or its intracellular messenger cGMP could
      significantly modulate the HR response to vagal nerve stimulation (VNS) in the
      anesthetized rabbit and isolated guinea pig atria. The NO donor molsidomine (0.2
      mg/kg iv) significantly enhanced the decrease in HR seen with right VNS (5 Hz, 5
      V, 30 s) in vivo. A qualitatively similar effect was seen with the NO donor
      sodium nitroprusside (SNP; 10 and 100 microM) during VNS in vitro. This effect
      was still present when the baseline shift in HR caused by SNP was eliminated by
      using the specific hyperpolarization-activated current antagonist 4-(N-ethyl-N
      phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD-7288, 1
      microM). The accentuated decrease in HR with SNP during VNS was mimicked by the
      stable analog of cyclic GMP, 8-bromoguanosine 3',5'-cyclic monophosphate (0.5
      mM). This, however, was not seen with bath application of the stable analog of
      acetylcholine, carbamylcholine chloride (100 nM). We conclude that excessive NO
      enhances the magnitude of the decrease in HR caused by VNS. This effect appears
      to involve a presynaptic action via a cGMP-dependent pathway because it was not
      mimicked by bath-applied carbamylcholine chloride.

PMID- 9931187
TI  - Norepinephrine response to exercise at the same relative intensity before and
      after endurance exercise training.
AB  - It is well documented that endurance exercise training results in a blunted
      norepinephrine (NE) response to exercise of a given absolute exercise intensity.
      However, it is not clear what effect training has on the catecholamine response
      to exercise of the same relative intensity because previous studies have provided
      conflicting results. The purpose of the present study was, therefore, to
      determine the catecholamine response to exercise of the same relative exercise
      intensity before and after endurance exercise training. Six women and three men
      [age 28 +/- 8 (SD) yr] performed 10 wk of training. Maximal O2 uptake (VO2 max)
      was determined during treadmill exercise. Fifteen-minute treadmill exercise bouts
      were performed at 60, 65, 70, 75, 80, and 85% of VO2 max before and after
      training. VO2 max was increased by 20% (from 39.2 +/- 7.7 to 46.9 +/- 8.1 ml. kg
      1. min-1; P < 0.05) in response to training. Plasma NE concentrations were higher
      (P < 0.05) during exercise at the same relative intensity after, compared with
      before, training at 65-85% of VO2 max. Differences between heart rates and plasma
      epinephrine concentrations after, compared with before, training were not
      statistically significant. These results provide evidence that the NE response to
      exercise is dependent on the absolute as well as the relative intensity of the
      exercise.

PMID- 9931188
TI  - Heat acclimation does not alter rat mesenteric artery response to norepinephrine.
AB  - Previous studies have shown that heat acclimation raises the temperature
      threshold for heat-induced splanchnic vasoconstriction in the rat (W. Haddad and
      M. Horowitz. Thermal Balance in Health and Disease, Advances in Pharmacological
      Sciences. Basel: Birkhauser, 1994, p. 203-208; M. Shochina, W. Haddad, U. Meiri,
      and M. Horo-witz. J. Therm. Biol. 21: 289-295, 1996). We tested the hypothesis
      that heat acclimation alters splanchnic resistance artery sensitivity to
      norepinephrine (NE). Male Sprague-Dawley rats (n = 5) were acclimated to 35
      degreesC ambient temperature for 5-8 wk. Control rats (n = 5) were maintained at
      22-23 degreesC ambient temperature for 5-7 wk. Small mesenteric artery segments
      (2- to 3-mm length, 100- to 340-micrometer ID) were isolated, cannulated at both
      ends, and pressurized to 50 mmHg. Artery luminal diameter was measured in
      response to cumulative doses of NE (10(-9) to 10(-5) M) by using video
      microscopy. NE dose response was measured at 37 and 43 degreesC bath
      temperatures. There were no differences in constriction responses to NE between
      acclimated and control rat arteries at either 37 or 43 degreesC. We conclude that
      acclimation does not alter rat mesenteric artery sensitivity to NE.

PMID- 9931190
TI  - Molecular-weight-dependent effects of nonanticoagulant heparins on allergic
      airway responses.
AB  - We have hypothesized that antiallergic activity of inhaled heparin is molecular
      weight dependent and mediated by "nonanticoagulant fractions" (NAF-heparin).
      Therefore, we studied comparative effects of high-, medium-, and ultralow
      molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute
      bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in
      allergic sheep. Specific lung resistance was measured in 23 allergic sheep,
      before and immediately after challenge with Ascaris suum antigen, without and
      after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated
      before and 2 h postantigen as the cumulative provocating dose of carbachol in
      breath units, which increased specific lung resistance by 400%. NAF-heparins
      attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin
      (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing
      50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n =
      8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg),
      whereas ULMW NAF-heparin (n = 7) was the most effective agent (ABR ID50 = 0.4
      mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in
      attenuating antigen-induced AHR when administered "after" antigen challenge and
      failed to inhibit the bronchoconstrictor response to carbachol and histamine. In
      15 additional sheep, segmental antigen challenge caused a marked increase in
      histamine in bronchoalveolar lavage fluid that was not prevented by any of the
      inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled
      heparin is independent of its anticoagulant action and resides in the <2,500 ULMW
      chains. The antiallergic activity of NAF-heparins is mediated by an unknown
      biological action and may have therapeutic potential.

PMID- 9931189
TI  - Cardiovascular and hemorheological effects of three modified human hemoglobin
      solutions in hemodiluted rabbits.
AB  - The cardiovascular effects of human albumin (Alb) and three human hemoglobin (Hb)
      solutions, dextran-benzene-tetracarboxylate Hb, alphaalpha-crosslinked Hb, and o
      raffinose-polymerized Hb were compared in anesthetized rabbits undergoing acute
      isovolemic hemodilution with Hct reduction from 41.4 +/- 2.7 to 28.8 +/- 1.6%.
      The impact of the vasoconstricting properties of Hb was examined by measuring
      heart rate (HR), mean arterial pressure (MAP), abdominal aortic, and femoral
      arterial blood flow, vascular resistance (VR), and aortic distension during the
      first 3 h after hemodilution. The impact of the hemorheological parameters was
      assessed by measurements of hemodiluted blood viscosity. In contrast to Alb, the
      Hb solutions elicited an immediate increase in MAP (20-38%). The effects of Alb
      and Hb solutions on HR, as well as on aortic and femoral arterial blood flow,
      were similar. VR decreased with Alb (20-28%) and increased with all three Hb
      solutions (30-90%), but the MAP and VR rising trends were different with each Hb
      solution. Aortic distension decreased in Hb groups compared with the Alb group
      for the first 60 min. The viscosity of hemodiluted blood was similar for all
      groups at high shear rates but was dependent on the viscosity of the solutions at
      low shear rates. We conclude that the vasoconstriction elicited by the Hb
      solutions overrides the vasodilation associated with viscosity changes due to
      hemodilution and would be the major factor responsible to the cardiovascular
      changes.

PMID- 9931191
TI  - Effect of concentric and eccentric muscle actions on muscle sympathetic nerve
      activity.
AB  - The purpose of this study was to determine the effects of concentric (Con) and
      eccentric (Ecc) muscle actions on leg muscle sympathetic nerve activity (MSNA).
      Two protocols were utilized. In protocol 1, eight subjects performed Con and Ecc
      arm curls for 2 min, with a resistance representing 50% of one-repetition maximum
      for Con curls. Heart rate (HR) and mean arterial pressure (MAP) were greater (P <
      0. 05) during Con than during Ecc curls. Similarly, the MSNA was greater (P <
      0.05) during Con than during Ecc curls. In protocol 2, eight different subjects
      performed Con and Ecc arm curls to fatigue, followed by postexercise muscle
      ischemia, by using the same resistance as in protocol 1. Endurance time was
      significantly greater for Ecc than for Con curls. The increase in HR, MAP, and
      MSNA was greater (P < 0.05) during Con than during Ecc curls. However, when the
      data were normalized as a function of endurance time, the differences in HR, MAP,
      and MSNA between Con and Ecc curls were no longer present. HR, MAP, and MSNA
      responses during postexercise muscle ischemia were similar for Con and Ecc curls.
      Con curls elicited greater increase (P < 0.05) in blood lactate concentration
      than did Ecc curls. In summary, Con actions contribute significantly more to the
      increase in cardiovascular and MSNA responses during brief, submaximal exercise
      than do Ecc actions. However, when performed to a similar level of effort (i.e.,
      fatigue), Con and Ecc muscle actions elicit similar cardiovascular and MSNA
      responses. These results indicate that the increase in MSNA during a typical bout
      of submaximal dynamic exercise is primarily mediated by the muscle metaboreflex,
      which is stimulated by metabolites produced predominantly during Con muscle
      action.

PMID- 9931193
TI  - Structure-function relationships in the pulmonary arterial tree.
AB  - Knowledge of the relationship between structure and function of the normal
      pulmonary arterial tree is necessary for understanding normal pulmonary
      hemodynamics and the functional consequences of the vascular remodeling that
      accompanies pulmonary vascular diseases. In an effort to provide a means for
      relating the measurable vascular geometry and vessel mechanics data to the mean
      pressure-flow relationship and longitudinal pressure profile, we present a
      mathematical model of the pulmonary arterial tree. The model is based on the
      observation that the normal pulmonary arterial tree is a bifurcating tree in
      which the parent-to-daughter diameter ratios at a bifurcation and vessel
      distensibility are independent of vessel diameter, and although the actual
      arterial tree is quite heterogeneous, the diameter of each route, through which
      the blood flows, tapers from the arterial inlet to essentially the same terminal
      arteriolar diameter. In the model the average route is represented as a tapered
      tube through which the blood flow decreases with distance from the inlet because
      of the diversion of flow at the many bifurcations along the route. The taper and
      flow diversion are expressed in terms of morphometric parameters obtained using
      various methods for summarizing morphometric data. To help put the model
      parameter values in perspective, we applied one such method to morphometric data
      obtained from perfused dog lungs. Model simulations demonstrate the sensitivity
      of model pressure-flow relationships to variations in the morphometric
      parameters. Comparisons of simulations with experimental data also raise
      questions as to the "hemodynamically" appropriate ways to summarize morphometric
      data.

PMID- 9931192
TI  - Rat hindlimb muscle blood flow during level and downhill locomotion.
AB  - During eccentrically biased exercise (e.g., downhill locomotion), whole body
      oxygen consumption and blood lactate concentrations are lower than during level
      locomotion. These general systemic measurements indicate that muscle metabolism
      is lower during downhill exercise. This study was designed to test the hypothesis
      that hindlimb muscle blood flow is correspondingly lower during downhill vs.
      level exercise. Muscle blood flow (determined by using radioactive microspheres)
      was measured in rats after 15 min of treadmill exercise at 15 m/min on the level
      (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles
      was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml.
      min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/-
      21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to
      ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/
      5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When
      individual extensor and flexor muscle flows were summed, total flow to the leg
      was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min).
      These data indicate that muscle blood flow and metabolism are lower during
      eccentrically biased exercise but are not uniformly reduced in all active
      muscles; i.e., flows are equivalent in several ankle extensor muscles and higher
      in ankle flexor muscles.

PMID- 9931194
TI  - Effects of chronic run training on Na+-dependent Ca2+ efflux from rat left
      ventricular myocytes.
AB  - The effects of endurance run training on Na+-dependent Ca2+ regulation in rat
      left ventricular myocytes were examined. Myocytes were isolated from sedentary
      and trained rats and loaded with fura 2. Contractile dynamics and fluorescence
      ratio transients were recorded during electrical pacing at 0.5 Hz, 2 mM
      extracellular Ca2+ concentration, and 29 degreesC. Resting and peak cytosolic
      Ca2+ concentration ([Ca2+]c) did not change with exercise training. However,
      resting and peak [Ca2+]c increased significantly in both groups during 5 min of
      continuous pacing, although diastolic [Ca2+]c in the trained group was less
      susceptible to this elevation of intracellular Ca2+. Run training also
      significantly reduced the rate of [Ca2+]c decay during relaxation. Myocytes were
      then exposed to 10 mM caffeine in the absence of external Na+ or Ca2+ to trigger
      sarcoplasmic reticular Ca2+ release and to suppress cellular Ca2+ efflux. This
      maneuver elicited an elevated steady-state [Ca2+]c. External Na+ was then added,
      and the rate of [Ca2+]c clearance was determined. Run training significantly
      reduced the rate of Na+-dependent clearance of [Ca2+]c during the caffeine
      induced contractures. These data demonstrate that the removal of cytosolic Ca2+
      was depressed with exercise training under these experimental conditions and may
      be specifically reflective of a training-induced decrease in the rate of
      cytosolic Ca2+ removal via Na+/Ca2+ exchange and/or in the amount of Ca2+ moved
      across the sarcolemma during a contraction.

PMID- 9931195
TI  - Effects of acetaminophen and ibuprofen on renal function in anesthetized normal
      and sodium-depleted dogs.
AB  - In certain conditions, renal prostaglandins (PGs) are important determinants of
      kidney function. Under these "renal PG-dependent states," pharmacological
      inhibition of vasodilatory PG may result in excessive renal vasoconstriction and
      adversely affect kidney function. The purposes of this study were to determine
      whether acetaminophen (Acet), a weak PG-synthesis inhibitor, influences kidney
      function in the renal PG-dependent state of anesthesia and sodium depletion.
      Comparisons were made with ibuprofen (Ibu). Measurements of PGE2 excretion were
      used to assess renal PG synthesis. Acet (15 mg/kg) and Ibu (10 mg/kg) both
      decreased renal blood flow and glomerular filtration rate by approximately 20-30%
      in normal, anesthetized, sodium-replete dogs. Although Acet produced similar
      changes in renal blood flow and glomerular filtration rate in the low-sodium
      dogs, Ibu caused a significantly greater renal vasoconstriction (64 +/- 10%) in
      these animals. Both Acet and Ibu inhibited urinary PGE2 excretion in sodium
      replete and low-sodium dogs. Ibu tended to have a greater and more prolonged
      effect than did Acet. These results suggest that Acet alters PGE2 excretion and
      kidney function under renal PG-dependent conditions; the effects, however, are
      less severe than those seen with Ibu.

PMID- 9931196
TI  - Effects of acetaminophen and ibuprofen on renal function in the stressed kidney.
AB  - Exercise, salt restriction, and/or dehydration causes transient reductions in
      renal function that may be buffered by vasodilatory prostaglandins (PGs). Over
      the-counter (OTC) analgesics have the potential to alter renal hemodynamics by
      inhibiting renal PGs. Therefore, we tested the renal effects of the maximal
      recommended dose of acetaminophen (Acet, 4 g/day) and ibuprofen (Ibu, 1.2 g/day)
      vs. a placebo (Pl) in humans subjected to progressive renal stresses. After
      baseline measurements, 12 fit young (25 +/- 1 yr) men and women underwent 3 days
      of a low (10 meq/day)-sodium diet while taking one of the drugs or Pl (crossover
      design). Day 4 involved dehydration (-1.6% body wt) followed by 45 min of
      treadmill exercise (65% maximal O2 uptake) in the heat (36 degreesC). These
      combined stressors caused dramatic decreases in effective renal plasma flow,
      glomerular filtration rate (GFR), and sodium excretion. Baseline GFR (range: 118
      123 ml/min) decreased to 78 +/- 4, 73 +/- 5, and 82 +/- 5 ml/min postexercise in
      the Acet, Ibu, and Pl trials, respectively, with a significantly greater decrease
      in GFR in the Ibu trial (P < 0. 05 vs. Pl). OTC Ibu has small but statistically
      significant effects on GFR during exercise in a sodium- and volume-depleted
      state; OTC Acet was associated with no such effects.

PMID- 9931197
TI  - Effect of increasing central venous pressure during passive heating on skin blood
      flow.
AB  - Whole body heating in humans increases skin blood flow (SkBF) and decreases
      central venous pressure (CVP). This study sought to identify whether elevations
      in SkBF are augmented during passive heating if CVP is increased during the heat
      stress. Seven subjects were exposed to passive heating. Once SkBF was
      substantially elevated, 15 ml/kg warm saline were rapidly infused intravenously.
      Whole body heating significantly increased cutaneous vascular conductance and
      decreased CVP from 7.7 +/- 0.6 to 4.9 +/- 0.5 mmHg (P < 0.05). Saline infusion
      returned CVP to pre-heat-stress pressures (7.9 +/- 0.6 mmHg; P > 0.05) and
      significantly increased cutaneous vascular conductance relative to the period
      before saline administration. Moreover, saline infusion did not alter mean
      arterial pressure, pulse pressure, or esophageal temperature (all P > 0.05). To
      serve as a volume control, 15 ml/kg saline were rapidly infused intravenously in
      normothermic subjects. Saline infusion increased CVP (P < 0.05) without affecting
      mean arterial pressure, pulse pressure, or cutaneous vascular conductance (all P
      > 0.05). These data suggest that cardiopulmonary baroreceptor unloading during
      passive heating may attenuate the elevation in SkBF in humans, whereas loading
      cardiopulmonary baroreceptors in normothermia has no effect on SkBF.

PMID- 9931198
TI  - Expiratory flow limitation during exercise in competition cyclists.
AB  - In some trained athletes, maximal exercise ventilation is believed to be
      constrained by expiratory flow limitation (FL). Using the negative expiratory
      pressure method, we assessed whether FL was reached during a progressive maximal
      exercise test in 10 male competition cyclists. The cyclists reached an average
      maximal O2 consumption of 72 ml. kg-1. min-1 (range: 67-82 ml. kg-1. min-1) and
      ventilation of 147 l/min (range: 122-180 l/min) (88% of preexercise maximal
      voluntary ventilation in 15 s). In nine subjects, FL was absent at all levels of
      exercise (i.e., expiratory flow increased with negative expiratory pressure over
      the entire tidal volume range). One subject, the oldest in the group, exhibited
      FL during peak exercise. The group end-expiratory lung volume (EELV) decreased
      during light-to-moderate exercise by 13% (range: 5-33%) of forced vital capacity
      but increased as maximal exercise was approached. EELV at peak exercise and at
      rest were not significantly different. The end-inspiratory lung volume increased
      progressively throughout the exercise test. The conclusions reached are as
      follows: 1) most well-trained young cyclists do not reach FL even during maximal
      exercise, and, hence, mechanical ventilatory constraint does not limit their
      aerobic exercise capacity, and 2) in absence of FL, EELV decreases initially but
      increases during heavy exercise.

PMID- 9931200
TI  - Gravity is an important but secondary determinant of regional pulmonary blood
      flow in upright primates.
AB  - Original studies leading to the gravitational model of pulmonary blood flow and
      contemporary studies showing gravity-independent perfusion differ in the recent
      use of laboratory animals instead of humans. We explored the distribution of
      pulmonary blood flow in baboons because their anatomy, serial distribution of
      vascular resistances, and hemodynamic responses to hypoxia are similar to those
      of humans. Four baboons were anesthetized with ketamine, intubated, and
      mechanically ventilated. Different colors of fluorescent microspheres were given
      intravenously while the animals were in the supine, prone, upright (repeated),
      and head-down (repeated) postures. The animals were killed, and their lungs were
      excised, dried, and diced into approximately 2-cm3 pieces with the spatial
      coordinates recorded for each piece. Regional blood flow was determined for each
      posture from the fluorescent signals of each piece. Perfusion heterogeneity was
      greatest in the upright posture and least when prone. Using multiple-stepwise
      regression, we estimate that 7, 5, and 25% of perfusion heterogeneity is due to
      gravity in the supine, prone, and upright postures, respectively. Although
      important, gravity is not the predominant determinant of pulmonary perfusion
      heterogeneity in upright primates. Because of anatomic similarities, the same may
      be true for humans.

PMID- 9931199
TI  - Breath ethane as a marker of reactive oxygen species during manipulation of diet
      and oxygen tension in rats.
AB  - Breath ethane, O2 consumption, and CO2 production were analyzed in 24-mo-old
      female Fischer 344 rats that had been fed continuously ad libitum (AL) or
      restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a
      glass chamber that was first flushed with air, then with a gas mixture containing
      12% O2. After equilibration, a sample of the outflow was collected in gas
      sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels
      were also directly monitored in the outflow of the chamber. O2 consumption and
      CO2 production increased for DR rats. Hypoxia decreased O2 consumption and CO2
      production for the AL-fed and DR rats. These changes reflect changes in metabolic
      rate due to diet and PO2. A significant decrease in ethane generation was found
      in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane
      decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of
      ethane generation increased, resulting in a DR-associated decrease in ethane from
      2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR
      reduces the level of oxidative stress.

PMID- 9931201
TI  - Experimental neonatal respiratory failure induced by lysophosphatidylcholine:
      effect of surfactant treatment.
AB  - The purpose of this study was to characterize the toxic effects of
      lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various doses of
      lyso-PC (from 0 to 40 mg/kg) were administered to near-term newborn rabbits. Lung
      thorax compliance during mechanical ventilation was significantly decreased by
      doses >/=10 mg/kg, and static lung volumes during deflation were decreased by
      doses >/=20 mg/kg. Using the same experimental model, we investigated the effects
      of modified porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC
      at birth and treated simultaneously with surfactant showed a satisfactory
      therapeutic response, whereas those treated after 30 min failed to respond. These
      animals also had a much larger leak of albumin into the air spaces and an
      elevated minimum surface tension of the lavage fluid in a pulsating bubble
      surfactometer, suggesting inactivation of the exogenous surfactant. Timing of
      surfactant administration may thus be essential for the therapeutic effect in
      this experimental model of acute lung injury.

PMID- 9931202
TI  - Regional clearance of solute from peripheral airway epithelia: recovery after
      sublobar exposure to ozone.
AB  - The influence of local exposure to ozone (O3) on respiratory epithelial
      permeability of sublobar lung segments was studied by using aerosolized 99mTc
      diethylenetriamine pentaacetic acid (DTPA; mol wt, 492). Two bronchoscopes were
      inserted through an endotracheal tube in anesthetized, mechanically ventilated,
      mixed breed dogs and were wedged into sublobar bronchi located in the right and
      left lower lobes, respectively. Segments were ventilated via the bronchoscope
      with 5% CO2 in air delivered at 200 ml/min, and an aerosol of 99mTc-DTPA was
      generated and delivered through the scope and into the sublobar segment over a 30
      s period. Clearance of 99mTc-DTPA was measured simultaneously from right and left
      lower lung segments at baseline and 1, 7, and 14 days after a 6-h sublobar
      exposure to filtered air or 400 parts per billion O3. O3 treatment significantly
      decreased the clearance halftime (t50) of 99mTc-DTPA by 50% from the baseline
      mean of 32.3 to 16.0 min at 1 day postexposure. After 7 days of recovery, t50 was
      still reduced by 28. 8%; however, by 14 days postexposure, clearance of 99mTc
      DTPA had recovered, and the t50 had a mean value of 30.0 min. 99mTc-DTPA
      clearance was not altered by exposure to filtered air, and t50 values were
      comparable to baseline at 1, 7, and 14 days postexposure. These results reveal
      that a single local exposure to O3 increases transepithelial clearance, but only
      for epithelia directly exposed to O3, and that 7-14 days of recovery are required
      before permeability to small-molecular-weight solutes returns to normal.

PMID- 9931203
TI  - Infrared CO2 analyzer error: an effect of background gas (N2 and O2).
AB  - Three infrared CO2 analyzers were tested for the effect of background gases: the
      Ametek CD-3A (Ametek, Thermox Instruments Division, Pittsburgh, PA), the Drager
      Multiwarn P CO2 (Drager, L ubeck, Germany), and the Servomex 1440 (Servomex,
      Crowborough, East Sussex, UK). Various CO2 concentrations were prepared with
      Wosthoff precision pumps (H. Wosthoff, Bochum, Germany). Calibration with a
      different background gas (O2 or N2) caused a similar but systematic error in the
      CO2 readings of all three analyzers. When the CO2 analyzers were calibrated with
      N2 as the background gas, the CO2 reading in an O2-enriched atmosphere was 8%
      lower than the true value. Conversely, calibration with O2 as the background gas
      resulted in a 10% overestimation of CO2 levels when N2 was the background gas.
      This error may be important in a few fields of respiratory physiology.

PMID- 9931204
TI  - Diaphragmatic lipid peroxidation in chronically loaded rats.
AB  - Recent work indicates that free radical-mediated lipid peroxidation takes place
      within the diaphragm on strenuous contraction. This phenomenon has only been
      demonstrated using fairly artificial experimental models and has not been studied
      during the type of sustained respiratory loading typically seen in patients with
      lung disease. The purpose of the present study was to measure the levels of
      several biochemical markers of protein oxidation (protein carbonyl levels) and
      lipid peroxidation (8-isoprostane, reduced glutathione, and oxidized glutathione
      levels) in diaphragms of rats subjected to chronic respiratory loading.
      Respiratory loading was accomplished by tracheal banding; groups of animals were
      loaded for 4, 8, or 12 days, and a group of sham-operated unloaded animals was
      used as controls. After loading, animals were killed, diaphragm contractility was
      assessed in vitro by using a portion of the excised diaphragm, and the remaining
      diaphragm and the soleus muscles were used for biochemical analysis. We found
      diminished force generation in diaphragms from all groups of banded animals
      compared with muscles from controls. For example, twitch force averaged 7.8 +/-
      0.8 (SE) N/cm2 in unloaded animals and 4.0 +/- 0.4, 3.0 +/- 0.4, and 3.4 +/- 0.4
      N/cm2 in animals loaded for 4, 8, and 12 days, respectively (P < 0.0001). Loading
      also elicited increases in diaphragmatic protein carbonyl concentrations (P <
      0.001), and the time course of alterations in carbonyl levels paralleled loading
      induced alterations in the diaphragm force-frequency relationship. Although
      loading was also associated with increases in diaphragmatic 8-isoprostane levels
      (P < 0.003) and reductions in diaphragm reduced glutathione levels (P < 0.003),
      the time course of changes in these latter parameters did not correspond to
      alterations in force. Soleus glutathione and carbonyl levels were not altered by
      banding. We speculate that respiratory loading-induced alterations in
      diaphragmatic force generation may be related to free radical-mediated protein
      oxidation, but not to free radical-induced lipid peroxidation.

PMID- 9931205
TI  - Relationship between histamine and physiological changes during the early
      response to nasal antigen provocation.
AB  - To investigate the temporal relationships of mediator release and physiological
      changes during the early response to allergen, we challenged allergic individuals
      intranasally with antigen and followed their responses. This was done by using
      small filter paper disks to challenge one nostril and collect secretions from
      both the challenged and the contralateral nostril, thus enabling us to evaluate
      the nasonasal reflex. There was a significant increase in sneezing after allergen
      challenge that peaked within 2 min and returned to baseline. The weights of nasal
      secretions as well as nasal symptoms increased immediately and remained
      significantly elevated for 20 min in both nostrils. Nasal airway resistance
      increased slowly, reaching its peak at approximately 6 min after challenge on the
      ipsilateral side, but it did not change on the contralateral side. Histamine
      levels peaked 30 s after removal of the allergen disk on the side of challenge,
      whereas albumin levels peaked after those of histamine. Lactoferrin paralleled
      the increase in secretion weights and occurred in both nostrils. Increasing doses
      of antigen produced dose-dependent increases in all parameters, whereas control
      challenges produced no response. These studies describe a human model for the
      evaluation of the allergic response that is capable of simultaneously measuring
      mediator release and the physiological response, including the nasonasal reflex.
      This model should prove useful in studying the mechanism of allergic rhinitis in
      humans.

PMID- 9931206
TI  - Liver AMP-activated protein kinase and acetyl-CoA carboxylase during and after
      exercise.
AB  - Exercise induces a decline in liver malonyl-CoA, an inhibitor of carnitine
      palmitoyltransferase-1. The purpose of these experiments was to determine whether
      this decrease in malonyl-CoA is accompanied by an activation of AMP-activated
      protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (ACC). Rats were
      killed at rest, after 10 min of running at 32 m/min up a 15% grade or at 0, 15,
      or 60 min postexercise after 120 min of running at 16 m/min. There was no
      significant difference in AMPK and ACC activities after 120 min of exercise,
      although a trend toward a decrease in ACC and an increase in AMPK was noted 15
      min postexercise. After 10 min at 32 m/min, however, maximal ACC activity
      decreased from 487 +/- 27 to 280 +/- 39 nmol. g-1. min-1, and the activation
      constant for citrate activation of ACC increased from 5.9 to 12.5 mM. AMPK
      activity increased from a resting value of 4.7 +/- 0.4 to 9.8 +/- 2.0 pmol. mg-1.
      min-1 after exercise. These data provide indirect evidence of phosphorylation and
      inactivation of liver ACC during heavy exercise. In contrast, the decrease in
      malonyl-CoA during long-term, low-intensity exercise may occur by mechanisms
      other than phosphorylation of ACC.

PMID- 9931207
TI  - Critical closing pressure explains cerebral hemodynamics during the Valsalva
      maneuver.
AB  - The Valsalva maneuver (VM), a voluntary increase in intrathoracic pressure of
      approximately 40 mmHg, has been used to examine cerebral autoregulation (CA).
      During phase IV of the VM there are pronounced changes in mean arterial blood
      pressure (MABP), pulse interval, and cerebral blood flow (CBF), but the changes
      in CBF are of a much greater magnitude than those seen in MABP, a finding to date
      attributed to either a delay in activation of the CA mechanism or the inability
      of this mechanism to cope with the size and speed of the blood pressure changes
      involved. These changes in CBF also precede those in MABP, a pattern of events
      not explained by the physiological process of CA. Measurements of CBF velocity
      (transcranial Doppler) and MABP (Finapres) were performed in 53 healthy
      volunteers (aged 31-80 yr). By calculating beat-to-beat values of critical
      closing pressure (CCP) during the VM, we have found that this parameter suddenly
      drops at the start of phase IV, providing a coherent explanation for the large
      increase in CBF. If CCP is included in the estimation of cerebrovascular
      resistance, a temporal pattern more consistent with an autoregulatory response to
      the MABP overshoot is also found. CCP is intricately involved in the control of
      CBF during the VM and should be considered in the assessment of CA.

PMID- 9931208
TI  - Cerebral vasomotor reactivity at high altitude in humans.
AB  - The purpose of this study was twofold: 1) to determine whether at high altitude
      cerebral blood flow (CBF) as assessed during CO2 inhalation and during
      hyperventilation in subjects with acute mountain sickness (AMS) was different
      from that in subjects without AMS and 2) to compare the CBF as assessed under
      similar conditions in Sherpas at high altitude and in subjects at sea level.
      Resting control values of blood flow velocity in the middle cerebral artery
      (VMCA), pulse oxygen saturation (SaO2), and transcutaneous PCO2 were measured at
      4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas, and 13
      subjects at sea level. Responses of CO2 inhalation and hyperventilation on VMCA,
      SaO2, and transcutaneous PCO2 were measured, and the cerebral vasomotor
      reactivity (VMR = DeltaVMCA/PCO2) was calculated as the fractional change of VMCA
      per Torr change of PCO2, yielding a hypercapnic VMR and a hypocapnic VMR. AMS
      subjects showed a significantly higher resting control VMCA than did no-AMS
      subjects (74 +/- 22 and 56 +/- 14 cm/s, respectively; P < 0.001), and SaO2 was
      significantly lower (80 +/- 8 and 88 +/- 3%, respectively; P < 0.001). Resting
      control VMCA values in the sea-level group (60 +/- 15 cm/s), in the no-AMS group,
      and in Sherpas (59 +/- 13 cm/s) were not different. Hypercapnic VMR values in AMS
      subjects were 4.0 +/- 4.4, in no-AMS subjects were 5.5 +/- 4. 3, in Sherpas were
      5.6 +/- 4.1, and in sea-level subjects were 5.6 +/- 2.5 (not significant).
      Hypocapnic VMR values were significantly higher in AMS subjects (5.9 +/- 1.5)
      compared with no-AMS subjects (4.8 +/- 1.4; P < 0.005) but were not significantly
      different between Sherpas (3.8 +/- 1.1) and the sea-level group (2.8 +/- 0.7). We
      conclude that AMS subjects have greater cerebral hemodynamic responses to
      hyperventilation, higher VMCA resting control values, and lower SaO2 compared
      with no-AMS subjects. Sherpas showed a cerebral hemodynamic pattern similar to
      that of normal subjects at sea level.

PMID- 9931209
TI  - Comparison of femoral blood gases and muscle near-infrared spectroscopy at
      exercise onset in humans.
AB  - We hypothesized that near-infrared spectroscopy (NIRS) measures of hemoglobin
      and/or myoglobin O2 saturation (IR-SO2) in the vascular bed of exercising muscle
      would parallel changes in femoral venous O2 saturation (SfvO2) at the onset of
      leg-kicking exercise in humans. Six healthy subjects performed transitions from
      rest to 48 +/- 3 (SE)-W two-legged kicking exercise while breathing 14, 21, or
      70% inspired O2. IR-SO2 was measured over the vastus lateralis muscle
      continuously during all tests, and femoral venous and radial artery blood samples
      were drawn simultaneously during rest and during 5 min of exercise. In all gas
      breathing conditions, there was a rapid decrease in both IR-SO2 and SfvO2 at the
      onset of moderate-intensity leg-kicking exercise. Although SfvO2 remained at low
      levels throughout exercise, IR-SO2 increased significantly after the first minute
      of exercise in both normoxia and hyperoxia. Contrary to the hypothesis, these
      data show that NIRS does not provide a reliable estimate of hemoglobin and/or O2
      saturation as reflected by direct femoral vein sampling.

PMID- 9931210
TI  - Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure
      in the isolated heart.
AB  - A goal of clinicians caring for heart transplant recipients has been to use heart
      rate variability as a noninvasive means of diagnosing graft rejection. The
      determinants of beat-to-beat variability in the surgically denervated heart have
      yet to be elucidated. We used an isolated, blood buffer-perfused porcine heart
      preparation to quantitatively assess the relationship between coronary perfusion
      and sinus node automaticity. Hearts (n = 9) were suspended in a Langendorff
      preparation, and heart rate (HR) fluctuations were quantified while perfusion
      pressure was modulated between 70/50, 80/60, 90/70, and 100/80 mmHg at 0.067 Hz.
      In 32 of 32 recordings, the cross spectrum of perfusion pressure vs. HR showed
      the largest peak centered at 0.067 Hz. In eight of nine experiments during
      nonpulsatile perfusion, HR accelerated as perfusion pressure was increased from
      40 to 110 mmHg (mean increase 24.2 +/- 3.0 beats/min). HR increased 0.34
      beats/min per mmHg increase in perfusion pressure (least squares linear
      regression y = -25.8 mmHg + 0.34x; r = 0.88, P < 0.0001). Administration of low-
      and high-dose nitroglycerin (Ntg) resulted in a modest increase in flow but
      produced a significant decrease in HR and blunted the response of HR to changes
      in perfusion pressure (HR increase 0.26 beats. min-1. mmHg-1, r = 0.87, P <
      0.0001 after low-dose Ntg; 0.25 beats. min-1. mmHg-1, r = 0.78, P < 0.0001 after
      high-dose Ntg). These experiments suggest that sinus node discharge in the
      isolated perfused heart is mechanically coupled to perfusion pressure on a beat
      to-beat basis.

PMID- 9931211
TI  - Mechanism of mosaic attenuation of the lungs on computed tomography in induced
      bronchospasm.
AB  - The purpose of this study was to investigate whether hypoxic pulmonary
      vasoconstriction is the major determinant of the computed tomography (CT) pattern
      of mosaic attenuation in asthmatic patients with induced bronchoconstriction.
      Thin-section CT was performed at suspended full inspiration immediately and 30
      min after methacholine bronchoprovocation in 22 asthmatic subjects, who were
      randomly assigned to breathe room air (group A, n = 8), oxygen via nasal prongs
      at 5 l/min (group B, n = 8), and oxygen via face mask at 12 l/min (group C, n =
      6). CT changes were quantified in terms of global lung density and density in
      hypodense and hyperdense areas. Lung parenchymal density increases were greatest
      in group C and greater in group B than in group A, globally (P = 0.03) and in
      hypodense regions (P = 0.01). On bivariate analysis, the only change in cross
      sectional area was related to change in global density. In hypodense regions,
      density change was related both to reduction in cross-sectional area (P < 0.0005)
      and to oxygen administration (P = 0.01). After correction for changes in global
      lung density, only oxygen was independently related to density increase in
      hypodense areas (P = 0.02). In induced bronchoconstriction, the CT appearance of
      mosaic attenuation can be largely ascribed to hypoxic vasoconstriction rather
      than to changes in lung inflation.

PMID- 9931212
TI  - Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one
      legged knee extension.
AB  - The redistribution of blood flow (BF) in the abdominal viscera during right
      legged knee extension-flexion exercise at very low intensity [peak heart rate
      (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting,
      subjects performed a right-legged knee extension-flexion exercise every 6 s for
      20 min. BF was measured in the upper abdominal aorta (Ao), right common femoral
      artery (RCFA), and left common femoral artery (LCFA). Visceral BF (BFVis) was
      determined by the equation [BFAo - (BFRCFA + BFLCFA)]. A comparison with the
      change in BF (DeltaBF) preexercise showed a greater increase in DeltaBFRCFA than
      in DeltaBFAo during exercise. This resulted in a reduction of BFVis to 56% of its
      preexercise value or a decrease in flow by 1,147 +/- 293 (+/-SE) ml/min at the
      peak workload. Oxygen consumption correlated positively with DeltaBFAo,
      DeltaBFRCFA, and DeltaBFLCFA but inversely with DeltaBFVis during exercise and
      recovery. Furthermore, BFVis (% of preexercise value) correlated inversely with
      both an increase in HR (r = -0.89), and percent peak oxygen consumption (r = 
      0.99). This study demonstrated that, even during very-low-intensity exercise (HR
      <90 beats/min), there was a significant shift in BF from the viscera to the
      exercising muscles.

PMID- 9931213
TI  - Phosphorescence quenching method for measurement of intracellular PO2 in isolated
      skeletal muscle fibers.
AB  - Values of skeletal muscle intracellular PO2 during conditions ranging from rest
      to maximal metabolic rates have been difficult to quantify. A method for
      measurement of intracellular PO2 in isolated single skeletal muscle fibers by
      using O2-dependent quenching of a phosphorescent-O2 probe is described. Intact
      single skeletal muscle fibers from Xenopus laevis were dissected from the
      lumbrical muscle and mounted in a glass chamber containing Ringer solution at 20
      degreesC. The chamber was placed on the stage of an inverted microscope
      configured for epi-illumination. A solution containing palladium-meso-tetra (4
      carboxyphenyl) porphine bound to bovine serum albumin was injected into single
      fibers by micropipette pressure injection. Phosphorescence-decay curves (average
      of 10 rapid flashes) were recorded every 7 s from single cells (n = 24) in which
      respiration had been eliminated with NaCN, while the PO2 of the Ringer solution
      surrounding the cell was varied from 0 to 159 Torr. For each measurement, the
      phosphorescence lifetime was calculated at the varied extracellular PO2 by
      obtaining a best-fit estimate by using a monoexponential function. The
      phosphorescence lifetime varied from 40 to 70 microseconds at an extracellular
      PO2 of 159 Torr to 650-700 microseconds at 0 Torr. The phosphorescent lifetimes
      for the varied PO2 were used to calculate, by using the Stern-Volmer
      relationship, the phosphorescence-quenching constant (100 Torr-1. s-1), and the
      phosphorescence lifetime in a zero-O2 environment (690 microseconds) for the
      phosphor within the intracellular environment. This technique demonstrates a
      novel method for determining intracellular PO2 in isolated single skeletal muscle
      fibers.

PMID- 9931214
TI  - Aerosol probes of lung injury in a 28-wk longitudinal study of mild experimental
      emphysema in dogs.
AB  - After baseline measurements of lung mechanics, effective air space diameter
      (EAD), and aerosol dispersion (AD), three dogs were exposed to two treatments of
      aerosolized papain (3 ml of a 4% solution), and measurements were repeated during
      a 28-wk follow-up period. EAD and AD were measured with boluses of 0.7-micrometer
      particles of di-2-ethylhexl sebacate, with Pen (i.e., volumetric bolus
      penetration/total lung capacity) between 0.1 and 0.4. After papain exposure, EAD
      increased a mean of 28% (P < 0.0001) and AD (Pen = 0.3, 0.4) increased 4-7% (P <
      0.03). The progression of injury was indicated by increasing trends in total lung
      capacity (P < 0.05), residual volume (P < 0.05), and EAD (P = 0.06) through week
      18. There was no evidence of disease progression between weeks 18 and 28, whereas
      some of the data for individual dogs suggested partial recovery from lung injury
      at week 28. The results show that aerosol probes can detect and characterize mild
      lung injury in experimental emphysema.

PMID- 9931215
TI  - Mathematical models of diffusion-limited gas bubble dynamics in tissue.
AB  - Mathematical models of bubble evolution in tissue have recently been incorporated
      into risk functions for predicting the incidence of decompression sickness (DCS)
      in human subjects after diving and/or flying exposures. Bubble dynamics models
      suitable for these applications assume the bubble to be either contained in an
      unstirred tissue (two-region model) or surrounded by a boundary layer within a
      well-stirred tissue (three-region model). The contrasting premises regarding the
      bubble-tissue system lead to different expressions for bubble dynamics described
      in terms of ordinary differential equations. However, the expressions are shown
      to be structurally similar with differences only in the definitions of certain
      parameters that can be transformed to make the models equivalent at large tissue
      volumes. It is also shown that the two-region model is applicable only to bubble
      evolution in tissues of infinite extent and cannot be readily applied to bubble
      evolution in finite tissue volumes to simulate how such evolution is influenced
      by interactions among multiple bubbles in a given tissue. Two-region models that
      are incorrectly applied in such cases yield results that may be reinterpreted in
      terms of their three-region model equivalents but only if the parameters in the
      two-region model transform into consistent values in the three-region model. When
      such transforms yield inconsistent parameter values for the three-region model,
      results may be qualitatively correct but are in substantial quantitative error.
      Obviation of these errors through appropriate use of the different models may
      improve performance of probabilistic models of DCS occurrence that express DCS
      risk in terms of simulated in vivo gas and bubble dynamics.

PMID- 9931216
TI  - Simultaneous determination of muscle 31P and O2 uptake kinetics during whole body
      NMR spectroscopy.
AB  - Our understanding of O2 uptake (VO2) control mechanisms during exercise may be
      improved by the simultaneous determination of the kinetics of intramuscular high
      energy phosphate turnover and pulmonary VO2. We therefore developed a technique
      for remote gas-exchange analysis while subjects exercised in a whole body 1.5-T
      NMR system. Knee-extension exercise was performed against restraining rubber
      bands in the prone position. Free induction decays were acquired every 1,875 ms
      by using a transmit-receive coil, which was placed under the quadriceps. This
      allowed 31P spectra of intramuscular ATP, Pi, and creatine phosphate dynamics to
      be determined every 15 s. Airflow was measured with a custom-designed turbine and
      a 45-ft.-long cable to reach the volume-measuring module. This was located in an
      adjacent radio-frequency-shielded room, as was the respiratory mass spectrometer,
      which also used a 45-ft.-long sampling line. The respired gas profiles were not
      discernibly different from those that used the standard inlet; the increase in
      the delay was readily incorporated into the breathby-breath algorithm, allowing
      the VO2 kinetics to be determined in concert with those of intramuscular
      phosphate metabolism.

PMID- 9931217
TI  - Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence
      of pigmentation.
AB  - A method for noninvasive measurement of Hb O2 saturation (SO2) in retinal blood
      vessels by digital imaging was developed and tested. Images of vessels were
      recorded at O2-sensitive and O2-insensitive wavelengths (600 and 569 nm,
      respectively) by using a modified fundus camera with an image splitter coupled to
      an 18-bit digital camera. Retinal arterial SO2 was varied experimentally by
      having subjects breathe mixtures of O2 and N2 while systemic arterial SO2 was
      monitored with a pulse oximeter. Optical densities (ODs) of vascular segments
      were determined using a computer algorithm to track the path of reflected light
      intensity along vessels. During graded hypoxia the OD ratio (ODR = OD600/OD569)
      bore an inverse linear relationship to systemic SO2. Compensation for the
      influence of choroidal pigmentation significantly reduced variation in the
      arterial SO2 measurements among subjects. An O2 sensitivity of 0.00504 +/-
      0.00029 (SE) ODR units/%SO2 was determined. Retinal venous SO2 at normoxia was 55
      +/- 3.38% (SE). Breathing 100% O2 increased venous SO2 by 19.2 +/- 2.9%. This
      technique, when combined with blood flow studies in human subjects, will enable
      the study of retinal O2 utilization under experimental and various disease
      conditions.

PMID- 9931218
TI  - Measurement of tidal volume by using transthoracic impedance variations in rats.
AB  - The application of impedance pneumography for monitoring respiration in small
      animals has been limited by problems with calibration. With improved
      instrumentation, we describe the calibration of tidal volume in anesthetized
      rats. The detection of changes in voltage, reflecting the electrical impedance
      variations associated with respiration, was optimized by using disposable
      adhesive silver-silver chloride electrodes, advanced circuitry, and analog-to
      digital recording instrumentation. We found a linear relationship between change
      in impedance and tidal volume in individual rats (R2 >/= 98%), which was strongly
      influenced by rat weight. Consequently, a calibration equation incorporating
      change in impedance and rat weight was derived to predict tidal volume.
      Comparison of the predicted and true tidal volumes revealed a mean R2 >/= 98%,
      slopes of approximately 1, intercepts of approximately 0, and bias of
      approximately 0.07 ml. The predicted volumes were not significantly affected by
      either frequency of respiration or pulmonary edema. We conclude that impedance
      pneumography provides a valuable tool for the noninvasive measurement of tidal
      volume in anesthetized rats.

PMID- 9931219
TI  - Characteristics of the muscle mechanoreflex during quadriceps contractions in
      humans.
AB  - We examined muscle sympathetic nerve activity (MSNA) in the nonexercising lower
      limb during repetitive static quadriceps contraction paradigm at 25% maximal
      voluntary contraction in eight men. Subjects performed 20-s contractions with 5-s
      rest periods for up to 12 contractions. Although the workload was constant, we
      found that MSNA amplitude rose as a function of contraction number [0.6 ln
      (amplitude/min)/contraction]; this suggests chemical sensitization of the muscle
      reflex response. We employed signal-averaging techniques and then integrated the
      data to examine the onset latency of the MSNA response as a function of the 25-s
      contraction-rest period. We observed an onset latency of approximately 4-6 s.
      Moreover, although the onset latency did not appear to vary as a function of
      contraction number, the rate of MSNA increase took approximately four
      contractions to reach a steady-state rate of rise; this suggests contraction
      induced sensitization. The onset latency reported here is similar to findings in
      recent animal studies, but it is at odds with latencies determined in prior human
      handgrip contraction studies. We believe our data suggest that 1) mechanically
      sensitive afferents contribute importantly to the MSNA response to the paradigm
      employed and 2) these afferents may be sensitized by the chemical products of
      muscle contraction.

PMID- 9931220
TI  - Evaluation of a dot-blot method for identification of antibodies against
      extractable nuclear antigens and anti-cytoplasmic antibodies.

PMID- 9931221
TI  - Lead exposure and hearing effects in children in Katowice, Poland.
AB  - The objective of the study was to investigate the relationship between lead
      exposure and hearing in children in the Katowice region, an industrial area in
      Poland. Blood lead was determined using inductively coupled plasma mass
      spectrometry, with appropriate quality control. The concentrations of lead in
      blood (B-Pb) in 155 children, aged 4-14, ranged from 19 to 281 microg/L (0.09 to
      1.4 micromol/L), with a median of 72 microg/L (0.34 micromol/L). The hearing
      thresholds increased significantly with increasing blood lead levels at all
      investigated frequencies (0.5, 1, 2, 4, 6, and 8 kHz). The relationship also
      remained significant for B-Pb below 100 microg/L (0.48 micomol/L; n=107). The
      brainstem auditory evoked potential latency of wave I was significantly increased
      (also after adjustment for age) in the group of children with the highest blood
      lead levels (B-Pb above 100 microg/L, 0.48 micromol/L; n=51), compared to the
      group with the lowest ones (B-Pb below 46 microg/L, 0.22 micromol/L; n=51). The
      audiometric results clearly indicate that auditory function in children is
      impaired at a blood lead concentration even below 100 microg/L (0.5 micromol/L).

PMID- 9931222
TI  - Diluted mainstream cigarette smoke condensates activate estrogen receptor and
      aryl hydrocarbon receptor-mediated gene transcription.
AB  - BACKGROUND: Epidemiological data indicate that in females cigarette smoking
      exerts antiestrogenic effects that manifest clinically in an increased incidence
      of osteoporosis, earlier menopause, increased spot bleeding, and decreased risk
      of endometrial cancer for female smokers. The molecular mechanism of this effect
      is unclear; however, decreased serum estrogen levels in female smokers have been
      correlated with increased concentrations of the metabolite 2-hydroxyestrogen in
      females who smoke. Induction of estrogen metabolizing enzymes, CYP1A1 and 1A2, is
      one mechanism by which increased 2-hydroxyestrogen concentrations may occur. It
      has also been suggested that the estrogen receptor (ER) may contribute to this
      anti-estrogenic effect by binding to antagonist(s) in cigarette smoke. METHODS:
      Gel retardation analysis was employed to determine if diluted mainstream
      cigarette smoke condensates (DMCSCs) could activate the aryl hydrocarbon receptor
      (AhR). AhR-regulated ethoxyresorufin-O-deethylase (EROD) activity and dioxin
      response element (DRE)-mediated luciferase induction were assessed in Hepa1c1c7
      mouse hepatoma cells. A competitive ligand binding assay was utilized to
      determine if DMCSCs could bind to the ER. ER-dependent luciferase activity was
      assessed in MCF-7 cells. RESULTS: In gel retardation assays, DMCSCs induced a
      protein-DNA complex when incubated with a radiolabeled wild-type DRE
      oligonucleotide. The complex was effectively competed by excess unlabeled DRE but
      not by excess unlabeled mutant DRE. In Hepa1c1c7 mouse hepatoma cells transiently
      transfected with a DRE-regulated luciferase reporter gene, pGudluc1.1, treatment
      with DMCSCs resulted in a 23- and 25-fold increase in luciferase activity
      (P<0.01) and an 8.5- and 10.5-fold (P<0.01) induction in EROD activity,
      respectively. DMCSCs completely displaced bound tritiated E2 from the ER in a
      dose-dependent manner and induced ER-regulated luciferase activity significantly
      6-fold (P<0.01), representing 86% of the maximal induction observed with E2.
      CONCLUSIONS: DMCSCs can bind to and transcriptionally activate the AhR and ER
      nuclear receptors and cause induction of DRE- and ER-regulated genes. Further
      study is required to identify the specific compound(s) responsible for these
      activities.

PMID- 9931223
TI  - Age-associated alteration of blood thiol-group-related antioxidants in smokers.
AB  - Total blood glutathione and nonglutathione free sulfhydryl compounds, glutathione
      peroxidase, and glutathione S-transferase in erythrocytes and plasma and also
      lipid peroxides in plasma were investigated in 48 male smokers and 42 male
      nonsmokers. We found that the level of total blood glutathione was significantly
      increased in young smokers (age <40) but no such change was noted in aging
      smokers (age>/=40). The activities of glutathione peroxidase and glutathione S
      transferase in plasma were significantly decreased in young smokers and the
      plasma levels of these two enzymes and nonglutathione free sulfhydryl compounds
      were more drastically decreased in aging smokers. The average concentration of
      plasma lipid peroxides of the aging smokers (2.76+/-0.46 nmol/ml) was
      significantly higher than that of the aging nonsmokers (2.32+/-0. 41nmol/ml,
      P=0.049). On the other hand, the level of total blood glutathione was negatively
      correlated with the level of plasma lipid peroxides (r=-0.305, P=0.002) and was
      positively correlated with the smoking index (r=0.307, P=0.019) of all the study
      subjects under age control. These results indicate that the activities of
      glutathione peroxidase and glutathione S-transferase declined to a great extent
      under smoking-mediated oxidative stress in the blood of both young and aging
      smokers. Moreover, the compensatory generation of total blood glutathione may
      effectively prevent plasma lipids from peroxidation in young smokers, although
      the activities of glutathione peroxidase and glutathione S-transferase in plasma
      were decreased. By contrast, total blood glutathione was inadequate for such
      protection in the aging smokers. We suggest that supplementation of thiol-group
      related agents may be considered for the prevention or alleviation of oxidative
      stress in aging smokers, whose capability and capacity for the disposal of
      smoking-mediated free radicals and reactive oxygen species are compromised.

PMID- 9931225
TI  - Nitrate levels in drinking water in rural New York State.
AB  - To obtain an indication of the nitrate-nitrogen levels in drinking water in rural
      areas of upstate New York and the number of infants at risk for
      methemoglobinemia, 419 wells supplying drinking water to farms were tested.
      Farmers were identified through two programs run by the New York State Department
      of Health. The farmers were asked to complete a short questionnaire about the
      type and size of their farm and their well and to collect the water sample.
      Overall, nitrates were detectable in 95% of the wells tested (concentration
      levels greater than 0.05 mg/L) and 15.7% had levels which exceeded 10 mg/L.
      Fifteen percent of the wells tested from farms where infants resided were also
      elevated. Wells which were shallow, dug or located on large farms, or springs
      were more likely to have elevated concentrations of nitrates.

PMID- 9931224
TI  - Lead in plasma and whole blood from lead-exposed children.
AB  - In 31 children exposed to lead and 13 considerably less exposed children
      ("unexposed"), the plasma (Pb-P) concentrations ranged from 0.46 to 18.4 (median,
      2.4) and from 0.14 to 0.38 (median, 0.21) microg/L, respectively. Corresponding
      whole-blood concentrations (Pb-B) were 99-920 (median, 370) and 39-120 (median,
      66) microg/L, respectively. The relation between Pb-B and Pb-P was nonlinear;
      when Pb-P rose, the Pb-B increased relatively less. There was a close association
      between Pb-B and log Pb-P (r=0.95; P=0.0001). When these data were compared to
      previous data on adults, there was no major difference between children and
      adults in the Pb-B/Pb-P relation. Free erythrocyte protoporphyrins in blood were
      associated with Pb-P (r=0.75; P=0.0001) and Pb-B (r=0.90; P=0.0001). Also, there
      was an association between blood-hemoglobin concentration and Pb-P in both
      exposed (r=-0.67; P=0.0001) and unexposed (r=-0.67; P=0.01) children; the
      corresponding figures for Pb-B were r=-0.42; P=0.02, and r=-0.80; P=0.001,
      respectively. Thus, at least with regard to toxicity on hematopoiesis at high
      lead levels, Pb-P may be a more relevant indicator of exposure and risk than Pb
      B. Because the curved Pb-B/Pb-P relation indicates a saturation of binding sites
      for lead in red cells, exposure and risk at high lead levels may easily be
      underestimated from Pb-B data.

PMID- 9931226
TI  - Plasma 5-aminolevulinic acid concentration and lead exposure in children.
AB  - The relationship between concentration of 5-aminolevulinic acid in plasma (ALAP)
      and other biomarkers of lead exposure and effect was investigated in lead-exposed
      children. We measured ALAP by chemical derivatization and high-performance liquid
      chromatography with fluorescence detection. The study population consisted of 103
      children: 78 from a referral clinic for children with lead poisoning and 25 from
      a general pediatric clinic. Blood lead concentration (PbB), age, and ALAP were
      higher in lead clinic subjects than in general clinic subjects. ALAP was
      significantly correlated with PbB (Spearman r=0.38, P=0.0007) and free
      erythrocyte protoporphyrin concentration (r=0.41, P=0.0002) in lead clinic
      subjects. PbB was a significant predictor of ALAP (P=0.0001) by multiple linear
      regression in all subjects. The average PbB in the 3- to 12-month period prior to
      blood collection correlated with ALAP to the same degree that current PbB
      correlated with ALAP. Possible associations between ALAP and adverse health
      outcomes, particularly neurobehavioral effects, should be investigated in
      children to assess the predictive value of ALAP for these endpoints.

PMID- 9931228
TI  - Analysis of rapid alternating movements in Cree subjects exposed to methylmercury
      and in subjects with neurological deficits.
AB  - To quantify rapid alternating movements (RAMs) we used a simple prototype
      developed in our laboratory that requires the subject to rotate two hand-held
      foam spheres connected to optical encoders via flexible rods. Ninety-six
      participants, including 30 control subjects, 36 Cree subjects exposed to
      methylmercury, 21 subjects with Parkinson's disease, 6 subjects with cerebellar
      deficits, and 3 subjects with essential tremor, were involved in the study
      (though data for 5 were later removed). Twelve characteristics were developed and
      calculated from the raw data. Conditions examined included two hands at natural
      cadence (NC2), right and left hands separately at fast cadence (FCl), and both
      hands at fast cadence (FC2). Two ratios (FC2/NC2) and (FC2/FC1) combining these
      conditions were also examined. Test-retest reliability was >0.80 for most
      characteristics but was <0.70 for some characteristics, especially in the
      conditions executed at normal cadence. Correlations between characteristics and
      numbers of outliers with respect to the control group distribution were used to
      reduce the set of characteristics from 12 to 7 (i.e., duration, range, maximum
      slope, similarity in shape, smoothness, sharpness, and coherence). ANOVAs on the
      three largest groups generated significant results for most characteristics in
      the three conditions and the two ratios for Cree subjects and subjects with
      Parkinson's disease. ANOVAs on 3 age-matched groups (n=6) suggest that
      methylmercury affects the performance of the Cree subjects with the higher
      exposure, especially in terms of smoothness, sharpness, and coherence. These
      preliminary results suggest that this test is sufficiently specific and sensitive
      to characterize the performance of different groups of subjects. Ratios tend to
      improve discrimination for Cree subjects in a few characteristics but not for
      patients with Parkinson's disease.

PMID- 9931229
TI  - Effect of acute exposure of the organophosphate insecticide Rogor on some
      biochemical aspects of Clarias batrachus (Linnaeus).
AB  - Indian catfish (Clarias batrachus), a common fish of commercial importance, was
      exposed to a sublethal concentration (1/3 of 96 h LC50 value) of Rogor for
      periods ranging from 24 to 192 h. The changes in glycogen, lactate, lactate
      dehydrogenase, and glycogen phosphorylase (a, ab) contents of muscle tissue were
      studied. A gradual decrease in muscle glycogen and an increase in lactate
      contents were observed. The activity level of lactate dehydrogenase showed a
      sharp rise initially for 48 h followed by a decline after 96 and 192 h. The
      glycogen phosphorylase a and ab in muscle tissue enhanced in response to Rogor
      exposure.

PMID- 9931227
TI  - Quantitative analysis of rapid pointing movements in Cree subjects exposed to
      mercury and in subjects with neurological deficits.
AB  - To quantify rapid and precise proximo-distal movements, we have developed a
      simple system (eurythmokinesimeter or EKM) which requires the subject to touch
      alternately the center of proximal and distal targets with a stylus. Ninety-six
      participants, including 30 controls subjects, 36 Cree subjects exposed to
      mercury, 21 subjects with Parkinson disease, 6 with presumed cerebellar deficit,
      and 3 with essential tremor, participated in the study. A total of nine measures,
      including precision, imprecision, contact duration, unsureness, tremor, transit
      time, irregularity, speed, and Fitts' constant, were calculated. Test-retest
      reliability was above 0.8 for most measures and above 0.9 for many measures.
      Correlations between measures and number of outliers with respect to the control
      group distribution for each measure were used to reduce the set of measures to
      five (i.e., precision, imprecision, tremor, Fitts' constant, and irregularity).
      An ANOVA on the three largest groups generated significant results for tremor,
      Fitts' constant, and irregularity between the Cree and the control subjects and
      on Fitts' constant and irregularity between the subjects with Parkinson's disease
      and the control subjects. Three subgroups of the same mean age composed of six
      subjects each were selected. One was composed of Cree subjects with the highest
      level of mercury exposure, another with Cree subjects having a low level of
      mercury exposure, and a third with control subjects. An ANOVA on these three
      groups revealed a significant difference between both groups of Cree subjects and
      the control group for Fitts' constant and irregularity. These preliminary results
      suggest that the EKM system is able to discriminate the performance of different
      groups of subjects.

PMID- 9931230
TI  - A comparison of costs of universal versus targeted lead screening for young
      children.
AB  - The purposes of this study were to compare universal blood lead screening for
      young children versus targeting by a risk assessment questionnaire and to examine
      the cost implications of each approach. Costs reflect the total number of blood
      tests required and cost of specimen collection, handling, and testing per
      elevated case. The setting included the metropolitan areas of Minneapolis and St.
      Paul, Minnesota. Children (N=9603) from 17 community organizations had blood
      tests. In addition, each child's parent or guardian completed a questionnaire
      assessing potential risk for lead poisoning. Four different screening approaches
      are presented. Each screening approach is presented with associated costs of
      overall screening and cost per child identified at blood levels of >/=10
      microg/dl (N=1140) and >/=15 microg/dl (N=317). Based on the screening strategy
      selected and an estimate of $17 per blood test, total screening costs ranged from
      $91,596 to $165,945. The cost per child identified with elevated lead levels
      ranged from $361 to $523 at >/=15 and $105 to $146 at >/=10. Nine to 13% of
      children would not have been detected by policies other than universal screening.
      A geographically based approach was able to detect 90% of children with elevated
      blood levels at two-thirds the cost of universal screening. Blood tests would be
      taken for all children living within city limits. Those residing elsewhere would
      be tested only if answers to questionnaire items pertaining to age of housing,
      prior history of lead poisoning, or eating paint chips indicated risk. The new
      CDC guidelines suggest that screening be based on an assessment of housing,
      population demographics, and community risk and resources. This paper presents
      such an assessment.

PMID- 9931231
TI  - Accumulation kinetics of polycyclic aromatic hydrocarbons adsorbed to sediment by
      the mollusk Corbicula fluminea.
AB  - The accumulation kinetics in the freshwater mollusk Corbicula fluminea were
      measured for sediment-associated selected polycyclic aromatic hydrocarbons
      (PAHs), namely, anthracene (Ant), phenanthrene (Phe), pyrene (Pyr), and benzo [a]
      pyrene (BaP). The desorption from sediment to water was not only related to water
      solubility, but also depended on structural and physicochemical properties of
      PAHs (molecular weight, molecular area, octanol/water partition coefficient Kow).
      Uptake of PAHs by mollusks was very fast in the first 24 h and maximum for low
      molecular-weight compounds. Then animal concentrations decreased significantly
      after the first day for Ant and Phe, after the second day for Pyr, and after the
      second week for BaP (at this time the BaP concentration was higher than
      concentrations of the other PAHs). The kinetic data suggest that PAH uptake is
      related to desorption from sediment particles. Log PAH uptake is inversely
      related to log Kow. Bioavailability of sediment-sorbed PAHs declined with contact
      time between sediment and animals. Assimilation from ingested material may be
      significant for the more strongly sorbed compound (BaP). PAHs with low Kow values
      become biologically unavailable more rapidly and more efficiently excreted.

PMID- 9931232
TI  - Altered cholinesterase and monooxygenase levels in Daphnia magna and Chironomus
      riparius exposed to environmental pollutants.
AB  - Biochemical indices were investigated for their potential use as variables of
      sublethal toxicity in Daphnia (cholinesterase) and Chironomus (cholinesterase and
      biotransformation enzymes). Parathion, dichlorvos, and aldicarb caused dose
      related inhibition of cholinesterase (ChE) in 24-h bioassays with both species.
      Ratios of Daphnia and Chironomus ChE IC50 values to corresponding immotility EC50
      values derived from the same experiment covered the range 0.26 to 1.2. Estimates
      of the ChE inhibition caused by the immotility EC50 were in the range 53-99%
      below control activity. ChE IC50 values of dichlorvos, parathion, and aldicarb
      were 0.17, 0.61, and 95 microg/liter in Daphnia and 6.2, 2.9, and 27 microg/liter
      in Chironomus, respectively. Cytochrome P450-dependent monooxygenase activities
      (ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, and ethoxycoumarin
      O-deethylase) were detectable in Chironomus but not in Daphnia. Chironomus
      monooxygenase activities were significantly inhibited to about 30% of control
      values after 4 days of exposure to 50 microg/liter 3, 4-dichloroaniline but
      remained unchanged by 0.5 microg/liter parathion. An approximately 1.3-fold
      induction of monooxygenase activities was caused by the model inducer naphthalene
      (0.1mg/liter). These results suggest that cytochrome P450-dependent monooxygenase
      activities may be useful variables in toxicity tests with aquatic insects.

PMID- 9931233
TI  - Toxicity of chromium to activated sludge.
AB  - The work deals with the toxicity of hexavalent and trivalent chromium to
      activated sludge. Cr(VI) was added as K2Cr2O7, and Cr(III) as Cr2(SO4)3. Toxicity
      is expressed as the inhibition of respiratory activity of microorganisms present
      in activated sludge. Respiration was measured by two methods, by means of an
      oximeter with an oxygen electrode and by means of a manometric apparatus
      permitting continuous observation of biological oxygen demand (BOD). The equation
      of the normal distribution function was used to construct inhibition curves and
      to calculate effective concentration (EC50). The influence of exposure time was
      observed as was the influence of concentration of activated sludge on the value
      of EC50. The 1-h EC50 for Cr(VI) by the ISO method was determined to be in the
      range of 40-90 mg/liter. A greater scatter of measured values, 46-201mg/liter,
      was found for the first hour of exposure by the manometric method. In the case of
      Cr(III) only combined inhibition by chromium ions and pH was determined. The 0.5
      h EC50 was 49 mg/liter.

PMID- 9931234
TI  - Effects of dieldrin on life stages of the African catfish, Clarias gariepinus
      (Burchell).
AB  - Early life stages of Clarias gariepinus were found to be less sensitive to acute
      dieldrin toxicity than were those of Nile tilapia, Oreochromis niloticus; 96-h
      LC50 values for 37-day-old fry were 11. 7 and 4.95 microg liter-1, respectively.
      The growth of C. gariepinus fry was unaffected by 30 days of exposure to 2.4
      microg liter-1 dieldrin under static conditions with water renewal every 96 h,
      whereas growth of O. niloticus fry was significantly reduced. Adult C. gariepinus
      exposed to dieldrin for 30 days, with water changes every 96 h, rapidly absorbed
      dieldrin from aqueous solution. Dieldrin concentration was measured just before
      water changes and from an initial concentration of 4.0 microg liter-1, stabilized
      after 12 days at about 0.075 microg liter-1, indicating that a balance between
      uptake and excretion and metabolism had been achieved. Dieldrin accumulated in
      the tissues during these exposures, especially in the liver, where after 30 days
      the bioconcentration factor relative to initial concentration was about 900.
      Chronic exposure of C. gariepinus to dieldrin had no effect on blood hematocrit
      and hemoglobin, but appeared to slow the growth of catfish and had a clear
      negative effect on the reproductive potential of mature females.

PMID- 9931235
TI  - Effects of atmospheric pollution on a Lichenophagous lepidopteran.
AB  - Terrestrial epiphytic algae were used to absorb atmospheric pollutants and this
      material was then fed to larvae of a bagmoth to assess the toxicological effects
      of the pollutants. Samples of algae were amended with pesticides to simulate
      agricultural spray drift and with vehicle exhaust gases to simulate road traffic
      emissions. Larval mortality, immobilization, and feeding were used as the
      toxicological endpoints. Feeding was the most sensitive of these, but clear dose
      response relationships were observed with all three endpoints. The effects of
      atmospheric pollution on an impacted environment were then investigated using
      these organisms. Algal samples were collected along a transect that included an
      area of arable farming, a motorway, and a woodland. Feeding was reduced when the
      larvae were fed algae from the areas proximal to the arable land and to the
      motorway. It is suggested that pesticide spray drift and vehicle exhaust
      emissions may have been the causal agents for these effects.

PMID- 9931236
TI  - Sublethal effects of phenol on the phospholipid fatty acid composition of carp
      erythrocyte plasma membrane.
AB  - The effect of different concentrations (5, 10, and 20 ppm) of phenol on the carp
      erythrocyte plasma membrane was examined following exposures of 48 and 96 h. The
      results indicated that the high concentrations of phenol pollutant led to an
      increase in phosphatidylcholine (PC) and eliminated phosphatidylinositol (PI),
      phosphatidylserine (PS), and phosphatidic acid (PA). The data also revealed that
      arachidonic acid (20:4 n-6) was present in the greatest amounts; its quantity in
      both low and high doses increased throughout the experimental period. The n-3
      fatty acids (eicosapentaenoic, 20:5 n-3, and docosahexaenoic acids, 22:6 n-3)
      displayed a fairly varied picture after exposure to phenol pollutant. Long-term
      exposure to higher phenol concentrations led to elimination of these acids and
      significantly decreased n-3/n-6 ratios.

PMID- 9931237
TI  - Effects of wood-related sterols on the reproduction, egg survival, and offspring
      of brown trout (Salmo trutta lacustris L.).
AB  - Maturing lake trout (Salmo trutta lacustris) of both sexes were exposed to 10 and
      20 microg/liter phytosterols, mainly ss-sitosterol, for 4.5 months prior to
      spawning. Eggs from preexposed females were artificially fertilized with milt
      from preexposed males in clean water, whereupon the eggs were incubated in clean
      water until hatching. Yolk sac fry were followed until swim-up, and mortality as
      well as deformities was recorded. The physiological status of the parent fish was
      documented, as was the occurrence of phytosterols in bile liquid and gonads. In
      addition, eggs from preexposed females were fertilized with milt from unexposed
      males to evaluate the existence of possible sex-linked differences. The results
      indicate a markedly increased dose-dependent egg mortality, smaller egg size, and
      lower mean weight of the the yolk sac stage larvae. There was a higher prevalence
      of deformed or otherwise diseased larvae, especially at the higher dose, but also
      in the groups where unexposed males were used for fertilization, indicating a
      female-linked effect mechanism. A causal link between effects on eggs and brood
      was obtained through a dose-dependent increase in phytosterols in the roe.
      Several physiological parameters (higher plasma estradiol, higher 7
      ethoxyresorufin O-deethylase activity) implied slower maturation of the exposed
      female fish, whereas indications of accelerated maturation were obtained for the
      male fish from the same groups. The results indicate that naturally occurring
      wood-derived compounds in pulp mill effluents may be responsible for reproductive
      impacts previously observed in fish both in the laboratory and in the receiving
      waters of pulp mill effluents. The results also suggest that more attention
      should be paid to process streams emanating from the unbleached part of the mill.

PMID- 9931239
TI  - Comparison of foliar and stem bioaccumulation of heavy metals by Corsican pines
      in the Mount Olympus area of Cyprus.
AB  - Early anthropogenic metalliferous activity on the island of Cyprus is outlined.
      Samples of Corsican pines, obtained from both a largely uncontaminated (control)
      and a metalliferous part of the Mount Olympus area of Cyprus, were analyzed by
      means of X-ray microanalysis. A total of 21 ions were recorded from the samples;
      in the contaminated site manganese, cobalt, nickel, copper, zinc, silver, and tin
      were bioaccumulated by the needles, while copper, zinc, and gold were
      bioaccumulated by the stems. Some elements, e.g., copper, were more positively
      bioaccumulated than others. Some implications of the findings are discussed.

PMID- 9931238
TI  - Apoptosis in dab (Limanda limanda) as possible new biomarker for anthropogenic
      stress.
AB  - Apoptosis, also known as programmed cell death, is a physiological and
      irreversible process in tissue homeostasis that leads to DNA fragmentation of
      multiples of 180-200 bp. Because apoptosis can be initiated not only by
      physiological stimuli but also by various chemical substances, the present paper
      investigates the suitability of apoptosis as a biomarker for biological effect
      monitoring in the marine environment. Aquarium experiments with dab (Limanda
      limanda) were carried out to examine the effects of exposure to cadmium, PCB 118,
      and PCB 77 (each 1 mg/kg fish wt) on apoptosis in dab liver. Determination of
      apoptosis was carried out by DNA gel electrophoresis and quantification of DNA
      fragments smaller than 1500 bp. In addition, accumulated amounts of cadmium, PCB
      118, and PCB 77 in dab liver were analyzed. Quantification of the three
      xenobiotics resulted in an accumulation of about factor 10(2)-10(4). Exposure to
      PCB 118 and cadmium resulted in an increase in apoptotic DNA fragmentation.
      Exposure to PCB 77 led mainly to cell death by necrosis.

PMID- 9931240
TI  - Activity of phase I and phase II detoxication enzymes in different cormus parts
      of Phragmites australis.
AB  - Enzymes of phase I and phase II of the xenobiotic detoxication pathway
      (ethoxyresorufin-O-deethylase, peroxidases, microsomal and soluble glutathione-S
      transferases) were measured in roots, stems, and leaves of Phragmites australis,
      revealing different enzyme activities in these parts. Highest enzyme activities
      were measured in the root followed by the leaf. Enzyme activities detected in the
      stem were low compared with those in the root and leaf. The high detoxication
      capacity of the root and the leaf might be due to very high exposure to
      xenobiotics and to the high levels of metabolism in these cormus parts. The
      function of the stem of Phragmites is mainly transportation, so a high
      detoxication level is not useful, as indicated by the low enzyme activities.

PMID- 9931241
TI  - A Daphnia magna first-brood chronic test: An alternative to the conventional 21
      Day chronic bioassay?
AB  - In this study a comparison was made of the results obtained in Daphnia magna
      chronic bioassays after first-brood release and after 21 days of exposure, using
      inhibition of normal reproduction and growth as effect criteria and EC10, EC20,
      EC50, no-observed-effect concentration (NOEC), and lowest-observed-effect
      concentration (LOEC) as statistical parameters. Test substances were sodium
      bromide (NaBr), 3,4-dichloroaniline (DCA), cadmium, and parathion. For NaBr, DCA,
      and cadmium, toxicity evaluated after the first-brood release was similar to
      toxicity evaluated after 21 days, using reproduction as end point. Parathion did
      not affect either reproduction or growth. Thus, LC50, NOEC, and LOEC were
      calculated using mortality as the endpoint for parathion. Results indicate that
      the period until release of the first brood is sufficient to predict the toxicity
      of some chemicals to D. magna. Values estimated on the basis of a logistic model
      (EC10, EC20, and EC50) were more appropriate than NOECs and LOECs for evaluating
      toxicity of the test substances. Furthermore, classic endpoints used for the
      evaluation of chronic toxicity (inhibition of normal reproduction and growth) may
      not be adequate to evaluate the sublethal toxicity of compounds that induce
      cumulative effects leading to mortality within the test period and causing no
      observable effects on the reproduction and growth of the species. Endpoints
      indicative of biochemical stress or effects on specific targets of the test
      compound may be useful in sublethal toxicity evaluation.

PMID- 9931242
TI  - Resistance of Eisenia fetida (Oligochaeta) to cadmium after long-term exposure.
AB  - The reliance on earthworms as test organisms in risk assessment studies of
      polluted environments raises the question whether they can evolve resistance,
      e.g., by adaptation to specific toxicants. Protection criteria may be biased if
      sensitivity data from adapted populations are used. Increased resistance to the
      heavy metal cadmium has not yet been determined for terrestrial Oligochaeta.
      Eisenia fetida was exposed to a sublethal concentration of cadmium sulfate for
      more than 10 generations. Clitellate worms from this culture were used in
      experiments to determine the extent of possible tolerance for the heavy metal.
      Preexposed animals as well as worms with no previous history of exposure to
      cadmium were exposed to a control substrate without cadmium and also to two
      substrates with 600 and 1200 microg g-1 cadmium. Changes in biomass, cocoon
      production, and hatching success were monitored. The results obtained indicated
      that in both substrates in which cadmium was present the preexposed worms
      performed better than the unexposed worms with respect to growth rate but not
      reproductively. In the substrate without cadmium the preexposed worms exhibited
      signs of poisoning after a few weeks. Preexposed and unexposed worms were also
      exposed to concentrations of 1500 to 4000 microg g-1 cadmium sulfate in an
      artisol medium for a period of 2 weeks. The preexposed worms survived higher
      concentrations of cadmium than the unexposed group and some specimens from the
      unexposed group had a gross increase in body fluids. It is concluded that worms
      with a long-term history of exposure to the metal developed resistance to
      cadmium.

PMID- 9931243
TI  - Biochemical and genotoxic responses of adult eel (Anguilla anguilla L.) to resin
      acids and pulp mill effluent: laboratory and field experiments.
AB  - The potential of a secondary-treated bleached kraft pulp mill effluent (BKPME)
      and resin acids (RAs) to induce liver ethoxyresorufin-O-deethylase (EROD)
      activity and erythrocytic nuclear abnormalities (ENAs) in adult Anguilla anguilla
      L. was investigated in laboratory and field experiments. Hepatic health was
      assessed by measurement of liver alanine transaminase (ALT). One single
      intraperitoneal injection of abietic acid (AA) or dehydroabietic acid (DHAA), at
      the same molar dose (14.7 micromol/kg), was given and fish were examined 3 days
      later. Only AA induced a significant increase in EROD activity while both RAs
      significantly increased the frequency of ENAs. A 3-day dose-response experiment
      (concentration range up to 2.7 microM) was also carried out for the same two
      water-diluted RAs. Both RAs induced a dose-related significant increase in EROD
      activity, presenting the same NOAEL (between 0.03 and 0.1 microM), while liver
      ALT activity significantly decreased. Both RAs revealed a mutagenic potential,
      measured as induction of ENAs, displaying the same NOAEL (between 0. 1 and 0.3
      microM). A laboratory experiment with 3 days of BKPME exposure revealed NOAELs
      between 12.5 and 25% for EROD activity and between 6.25 and 12.5% for ENA
      frequency. An additional laboratory experiment with 50% BKPME demonstrated that
      the minimal time necessary to induce a significant increase in EROD activity in
      the eel was 6 h. In a field experiment, caged eels were exposed in the river, at
      different distances (left bank: site 1-50 m; right bank: site 2-100 m, site 3-600
      m, site 4-2000 m) from the BKPME sewage outlet. Liver EROD activity significantly
      increased at 1 and 3 days of exposure, with the exception of site 2, whereas ENAs
      were induced after 3 days of exposure at site 3.

PMID- 9931245
TI  - DNA-sequence asymmetry directs the alignment of recombination sites in the FLP
      synaptic complex.
AB  - The FLP recombinase promotes site-specific recombination in the 2 micrometer
      circle of Saccharomyces cerevisiae. FLP recognizes a 48 bp target site (FLP
      recombination target, or FRT) consisting of three 13 bp protein binding sites, or
      symmetry elements, flanking an 8 bp spacer region. Efficient recombination also
      occurs with DNA substrates that have minimal FRT sites, consisting only of the
      spacer and two surrounding 13 bp symmetry elements arranged in inverse
      orientation; thus, the wild-type spacer sequence is the main asymmetric feature
      of the minimal recombination site. FLP carries out recombination with many
      minimal target sites bearing symmetric or asymmetric mutant spacer sequences;
      however, the overall directionality of recombination defined in terms of
      inversion or excision of a DNA domain is determined by spacer-sequence asymmetry.
      In order to evaluate the potential influence of spacer-sequence asymmetry on
      structures formed during early steps in recombination, we used electron
      microscopy to investigate the structure of the FLP synaptic complex, which is the
      intermediate protein-DNA complex involved in site pairing and strand exchange.
      Using linear substrate DNAs that have minimal FRTs with wild-type spacer
      sequences, we find that 85 to 90% of the FLP synaptic complexes examined contain
      the two FRTs aligned in parallel. This strong preference for parallel site
      alignment stands in contrast with prevailing models for lambda integrase-class
      recombination systems, which postulate antiparallel site alignment, and results
      from biophysical studies on synthetic, immobile four-way DNA junctions. Our
      results show that the strong preference for parallel alignment can be attributed
      to conformational preferences of Holliday junctions present in the synaptosome.

PMID- 9931244
TI  - Evidence for organochlorine contamination in tissues of salmonids in Lake Tahoe.
AB  - To evaluate the extent of organochlorine pollution in the Sierra Nevada
      ecosystem, residues of certain organochlorines in lake trout and Kokanee fish
      from Lake Tahoe, an alpine lake located between the Sierra Nevada Mountain Range
      and the Carson Range of California and Nevada, were analyzed. Multiresidue
      analysis in fish muscle revealed wet weight concentrations of total
      polychlorinated biphenyls (PCBs) in the range 18 to 430 ppb and of p,p'-DDE in
      the range 5 to 85 ppb in the two fish species studied. In one large lake trout
      sample (6.6 kg), which was studied in more detail as compared with others,
      residue levels of PCB (267 ppb), toxaphene (154 ppb), a chlordane mixture (78
      ppb), and a DDT mixture (154 ppb) were found in muscle. Full spectra of specific
      PCB congeners and p,p'-DDE were obtained from fish fat tissues and their
      identities were confirmed using gas chromatography/mass spectrometry (GC-MS). The
      results of total PCB analysis indicated that residues found in fish consisted
      mostly of moderately (tri- to tetrachloro-) to highly (penta- to heptachloro-)
      chlorinated biphenyls. For all fish residues analyzed, the best match to PCB
      residue profiles was with Aroclor 1260 or 1262.

PMID- 9931246
TI  - Recombination during reverse transcription: an evaluation of the role of the
      nucleocapsid protein.
AB  - The human immuno deficiency virus type 1 nucleocapsid protein 7 (HIV-1 NCp7) is a
      major component of the reverse transcription complex. Its effect on reverse
      transcription and homologous recombination has been studied in vitro under
      strictly identical experimental conditions. For high enzyme concentrations, NCp7
      did not stimulate DNA synthesis. The time-course for completion of reverse
      transcription as well as the processivity and the pattern of pausing were similar
      in the presence or absence of NCp7. However, the addition of NCp7 significantly
      affected the yield of the reaction, a decrease exacerbated as the length of the
      copied RNA increased. We attribute this phenomenon to a destabilization of the
      RNA/DNA duplex at intermediate stages of reverse transcription.In contrast, NCp7
      enhanced homologous recombination during synthesis mediated by HIV-1 RT (reverse
      transcriptase), as it did for Moloney murine leukemia virus RT. On naked RNA the
      process of recombination was dependent on the concentration of RT, suggesting
      that binding of RT to an intermediate of strand transfer was the limiting step.
      This dependence was relieved in the presence of NCp7. This effect does not imply
      a direct interaction between RT and NCp7, since similar results were obtained
      when NCp7 was substituted by the bacterial RNA chaperon StpA. The dominant effect
      of NCp7 is therefore most probably exerted at the level of condensation of the
      RNA templates, leading to the formation of productive interactions between the
      nascent DNA and the acceptor template.

PMID- 9931247
TI  - Effect of mutations in the A site of 16 S rRNA on aminoglycoside antibiotic
      ribosome interaction.
AB  - Decoding of genetic information occurs upon interaction of an mRNA codon-tRNA
      anticodon complex with the small subunit of the ribosome. The ribosomal decoding
      region is associated with highly conserved sequences near the 3' end of 16 S
      rRNA. The decoding process is perturbed by the aminoglycoside antibiotics, which
      also interact with this region of rRNA. Mutations of certain nucleotides in rRNA
      reduce aminoglycoside binding affinity, as previously demonstrated using a model
      RNA oligonucleotide system. Here, predictions from the oligonucleotide system
      were tested in the ribosome by mutation of universally conserved nucleotides at
      1406 to 1408 and 1494 to 1495 in the decoding region of plasmid-encoded bacterial
      16 S rRNA. Phenotypic changes range from the benign effect of U1406-->A or A1408-
      >G substitutions, to the highly deleterious 1406G and 1495 mutations that
      assemble into 30 S subunits but are defective in forming functional ribosomes.
      Changes in the local conformation of the decoding region caused by these
      mutations were identified by chemical probing of isolated 30 S subunits.
      Ribosomes containing 16 S rRNA with mutations at positions 1408, 1407+1494, or
      1495 had reduced affinity for the aminoglycoside paromomycin, whereas no
      discernible reduction in affinity was observed with 1406 mutant ribosomes. These
      data are consistent with prior NMR structural determination of aminoglycoside
      interaction with the decoding region, and further our understanding of how
      aminoglycoside resistance can be conferred.

PMID- 9931248
TI  - DNA molecules can drive the assembly of other DNA molecules into specific four
      stranded structures.
AB  - Single-stranded DNA molecules containing clustered G-repeats can be assembled
      into various four-stranded structures linked by G-quartets. Here, we report that
      such molecules can also drive the assembly of other DNA molecules containing G
      repeats into specific four-stranded structures. In these assays, the
      oligonucleotides 5'-CAGGCTGAGCAGGTACGGGGGAGCTGGGGTAGATTGGAATGTAG-3' (oligo D) and
      5'-CGGGGGAGCTGGGGT-3' (oligo B), consisting of sequences found in immunoglobulin
      switch regions, were annealed in a buffer containing K+ and the annealing
      products were analyzed by polyacrylamide gel electrophoresis. This analysis
      revealed that whereas annealing of each oligo alone produced four-stranded
      structures designated D2 and B2, annealing of mixtures containing both oligos
      produced additional complexes designated D2* and B2*. D2* and B2* were found to
      contain only D molecules and only B molecules, respectively. The yield of D2*
      increased and the yield of B2* decreased, as the concentration ratio oligo
      B/oligo D was increased. These results indicated that B can drive the assembly of
      D into D2* and D can drive the assembly of B into B2*. Further studies revealed
      that while the assembly of D2 followed a second order kinetics, the B-driven
      assembly of D2* followed a first order kinetics. Dimethyl sulfate footprinting
      indicated that both D2 and D2* are four-stranded structures containing two
      parallel and two antiparallel chains. In addition, annealing of D mixed with
      various B mutants showed that only mutants containing two G-clusters can drive
      the assembly of D2*. Based on these data, we propose that in the process of D2*
      assembly, a four-stranded intermediate containing B and D is formed and then
      dissociates into D2* and B in a rate-limiting first order reaction. Driver
      mechanisms of this type may cause formation of specific four-stranded structures
      at G-rich chromosomal sites, thereby regulating processes such as recombination
      and telomere synthesis.

PMID- 9931249
TI  - Role of the "YxGG/A" motif of Phi29 DNA polymerase in protein-primed replication.
AB  - We have analyzed the functional significance of the phi29 DNA polymerase "YxGG/A"
      motif in initiation and replication reactions involving the terminal protein (TP)
      as a primer. This motif, located between the proposed limits of the polymerase
      and exonuclease domains, has been shown to be very important for the coordination
      between synthesis and degradation in phi29 DNA polymerase. Mutations in this
      region affected the polymerization/exonucleolysis (pol/exo) balance, due to its
      importance for DNA template binding stability at both active sites. Here, we show
      that the YxGG/A motif of phi29 DNA polymerase is necessary for the formation of a
      stable complex between TP and phi29 DNA polymerase, affecting initiation and
      transition during replication of phi29 TP-DNA. The phenotypes in TP-primed
      reactions in nine of 11 mutant polymerases, showed reduced initiation and/or
      replication activities using TP-DNA as template. High dATP concentrations allowed
      the reduced initiation activities of some of these mutant polymerases to reach
      the wild-type level. The reduction in their affinity for the initiating
      nucleotide is likely due to their reduced interaction with the TP. Besides, the
      YxGG/A motif of phi29 DNA polymerase controls the pol/exo balance in the
      transition step immediately after TP-primed initiation, before DNA polymerase and
      TP dissociate. Thus, from the first elongation step, the phenotypes of the mutant
      polymerases parallel those obtained in DNA-primed replication: wild-type, high
      and low pol/exo balance. A detailed analysis of different transition
      intermediates suggests that mutants at the YxGG/A motif switch from interaction
      with TP to DNA once the TP has been extended with six nucleotides.

PMID- 9931250
TI  - The effect of a hydrophobic N-terminal probe on translational pausing of
      chloramphenicol acetyl transferase and rhodanese.
AB  - The effect on translational pausing of a hydrophobic probe, coumarin, at the N
      terminus of nascent peptides was investigated. Two different proteins, bacterial
      chloramphenicol acetyltransferase and bovine rhodanese, were synthesized by
      coupled transcription/translation in a cell-free system derived from Escherichia
      coli. Protein synthesis was initiated with N-formyl-Met-tRNAf or N-acetyl-S
      coumarin-Met-tRNAf. Cotranslational incorporation of the coumarin derivative
      generated nascent polypeptides with a hydrophobic residue at their N termini. The
      effect of the two N-terminal groups on the size distribution and quantity of the
      peptides formed by translational pausing was investigated. The N-terminal
      coumarin caused an accumulation of nascent chloramphenicol acetyltransferase
      peptides in the mass range of 3.5-4.0 kDa that reflects a delay in translation at
      this point. No similar effect on rhodanese pause-site peptides was observed. This
      effect on translational pausing cannot be explained by either mRNA secondary
      structure or rare codons and tRNA abundance. It is suggested that the effect of N
      terminal coumarin on translational pausing is the result of the interaction of
      the nascent peptide with components of the large ribosomal subunit along the path
      it follows between the peptidyl transferase center and the exit site on the
      distal surface.

PMID- 9931251
TI  - Model for lentivirus capsid core assembly based on crystal dimers of EIAV p26.
AB  - Two crystal forms of recombinant p26 capsid protein (CA) from the equine
      infectious anemia virus (EIAV) have in common an antiparallel four-helix bundle
      dimer interface between N-terminal domains (NTDs). The dimer interface provides a
      lenient scaffold to accommodate the wide sequence variation in these helices
      within lentivirus CA. Pairs of dimers weakly associate to form exact or
      approximate D2 symmetry tetramers. In one of the two crystal forms, the tetramers
      are linked via dimerization of C-terminal domains (CTDs). We propose that the
      observed NTD and CTD homodimer interactions are involved in the assembly of the
      lentivirus capsid. The NTD homodimer shape readily suggests a model for the
      mature capsid core, based on hexagonal packing with dimensions and surface
      topology resembling described EIAV capsid cores. Combining available data for
      human immunodeficiency virus and EIAV CA, we also propose an assembly pathway for
      maturation of the lentivirus capsid core following proteolytic cleavage of the
      gag polyprotein precursor.

PMID- 9931252
TI  - Cross-functional analysis of the Microviridae internal scaffolding protein.
AB  - The assembly of the viral structural proteins into infectious virions is often
      mediated by scaffolding proteins. These proteins are transiently associated with
      morphogenetic intermediates but not found in the mature particle. The genes
      encoding three Microviridae (phiX174, G4 and alpha3) internal scaffolding
      proteins (B proteins) have been cloned, expressed in vivo and assayed for the
      ability to complement null mutations of different Microviridae species. Despite
      divergence as great as 70% in amino acid sequence over the aligned length, cross
      complementation was observed, indicating that these proteins are capable of
      directing the assembly of foreign structural proteins into infectious particles.
      These results suggest that the Microviridae internal scaffolding proteins may be
      inherently flexible. There was one condition in which a B protein could not cross
      function. The phiX174 B protein cannot productively direct the assembly of the G4
      capsid at temperatures above 21 degreesC. Under these conditions, assembly is
      arrested early in the morphogenetic pathway, before the first B protein mediated
      reaction. Two G4 mutants, which can productively utilize the phiX174 B protein at
      elevated temperatures, were isolated. Both mutations confer amino acid
      substitutions in the viral coat protein but differ in their relative abilities to
      utilize the foreign scaffolding protein. The more efficient substitution is
      located in a region where coat-scaffolding interactions have been observed in the
      atomic structure and may emphasize the importance of interactions in this region.

PMID- 9931253
TI  - The preprotein translocase of the mitochondrial inner membrane: function and
      evolution.
AB  - Growing mitochondria acquire most of their proteins by the uptake of
      mitochondrial preproteins from the cytosol. To mediate this protein import, both
      mitochondrial membranes contain independent protein transport systems: the Tom
      machinery in the outer membrane and the Tim machinery in the inner membrane.
      Transport of proteins across the inner membrane and sorting to the different
      inner mitochondrial compartments is mediated by several protein complexes which
      have been identified in the past years. A complex containing the integral
      membrane proteins Tim17 and Tim23 constitutes the import channel for preproteins
      containing amino-terminal hydrophilic presequences. This complex is associated
      with Tim44 which serves as an adaptor protein for the binding of mtHsp70 to the
      membrane. mtHsp70, a 70 kDa heat shock protein of the mitochondrial matrix,
      drives the ATP-dependent import reaction of the processed preprotein after
      cleavage of the presequence. Preproteins containing internal targeting
      information are imported by a separate import machinery, which consists of the
      intermembrane-space proteins Tim9, Tim10, and Tim12, and the inner membrane
      proteins Tim22 and Tim54. The proteins Tim17, Tim22, and Tim23 have in common a
      similar topology in the membrane and a homologous amino acid sequence. Moreover,
      they show a sequence similarity to OEP16, a channel-forming amino acid
      transporter in the outer envelope of chloroplasts, and to LivH, a component of a
      prokaryotic amino acid permease, defining a new PRAT-family of preprotein and
      amino acid transporters.

PMID- 9931254
TI  - Isolation and characterization of a protein with high affinity for DNA: the
      glutamine synthetase of Thermus thermophilus 111.
AB  - In a search of proteins from the thermophilic bacterium Thermus thermophilus 111
      with a high affinity for DNA, the selected protein from this screening appears to
      be the glutamine synthetase (GS). The purified product gives one band in SDS
      polyacrylamide gel electrophoresis (53,700 Da). The N-terminal 32 residues have
      been identified and present an homology of 80% with the glutamine synthetase of
      Bacillus subtilis and 76% with that of Thermotoga maritima. The protein displays
      the characteristic dodecameric structure of the eubacteria glutamine synthetase.
      From a detailed study of the interaction of this protein with DNA by dark-field
      electron microscopy and agarose gel electrophoresis, it is concluded that double
      stranded DNA wraps the protein by a full turn of 150 bp length. An even number of
      GS molecules bound to a closed relaxed plasmid DNA does not alter its null
      topology. By using an inverted dimer DNA fragment, which contains twice a curved
      kinetoplast DNA insert in its central part, it is shown that DNA curvature rules
      the order in which GS binds to the DNA. DNA ends are also sites of high affinity
      for the GS. Supercoiling does not favor the binding of GS to the DNA with the
      exception of the apices that are by essence bent regions. By saturating a DNA
      molecule with GS one obtains a novel characteristic scalloped configuration in
      which the DNA undulates from one GS to the next. The DNA is condensed at least
      three times in these structures. By increasing the ratio of GS to DNA in solution
      the resulting material migrates as discrete bands relative to the free DNA in an
      agarose gel. By gel retardation and EM statistical distribution analysis of GS
      within the complexes, an average affinity constant of 10(7) M-1 was obtained. The
      potential implications of this novel interaction of the glutamine synthetase with
      DNA for the regulation of its own gene are briefly discussed.

PMID- 9931255
TI  - Structure of catalase-A from Saccharomyces cerevisiae.
AB  - The structure of the peroxisomal catalase A from the budding yeast Saccharomyces
      cerevisiae, with 515 residues per subunit, has been determined and refined to 2.4
      A resolution. The crystallographic agreement factors R and Rfree are 15.4% and
      19.8%, respectively. A tetramer with accurate 222-molecular symmetry is located
      in the asymmetric unit of the crystal. The conformation of the central core of
      catalase A, about 300 residues, remains similar to the structure of catalases
      from distantly related organisms. In contrast, catalase A lacks a carboxy
      terminal domain equivalent to that found in catalase from Penicillium vitalae,
      the only other fungal catalase structure available. Structural peculiarities
      related with the heme and NADP(H) binding pockets can be correlated with
      biochemical characteristics of the catalase A enzyme. The network of molecular
      cavities and channels, filled with solvent molecules, supports the existence of
      one major substrate entry and at least two possible alternative pathways to the
      heme active site. The structure of the variant protein Val111Ala, also determined
      by X-ray crystallography at 2.8 A resolution, shows a few, well-localized,
      differences with respect to the wild-type enzyme. These differences, that include
      the widening of the entry channel in its narrowest point, provide an explanation
      for both the increased peroxidatic activity and the reduced catalatic activity of
      this mutant.

PMID- 9931256
TI  - Crystal structure of ovine interferon-tau at 2.1 A resolution.
AB  - Ovine interferon-tau (ovIFN-tau) is a pregnancy recognition hormone required for
      normal embryonic development in sheep. In addition to its novel role in
      reproductive physiology, ovIFN-tau displays antiviral and antiproliferative
      activities similar to the IFN-alpha subtypes. To probe the structural basis for
      its unique activity profile, the crystal structure of ovIFN-tau has been
      determined at 2.1 A resolution. The fold of ovIFN-tau is similar to the
      previously determined crystal structures of human IFN-alpha2b and human and
      murine IFN-beta, which each contain five alpha-helices. Comparison of ovIFN-tau
      with huIFN-alpha2b, huIFN-beta, and muIFN-beta reveals unexpected structural
      differences that occur in regions of considerable sequence identity.
      Specifically, main-chain differences up to 11 A occur for residues in helix A,
      the AB loop, helix B, and the BC loop. Furthermore, these regions are known to be
      important for receptor binding and biological activity. Of particular interest, a
      buried ion pair is observed in ovIFN-tau between Glu71 and Arg145 which displaces
      a conserved tryptophan residue (Trp77) from the helical bundle core. This ion
      pair represents a major change in the core of ovIFN-tau compared to huIFN
      alpha2b. Based on amino acid sequence comparisons, these ovIFN-tau structural
      features may be conserved in several human IFN-alpha subtypes and IFN-omega. The
      structure identifies potential problems in interpreting site-directed mutagenesis
      data on the human IFN-alpha family that consists of 12 proteins.

PMID- 9931257
TI  - The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro
      Phe-chloromethylketone: structural explanation for its dipeptidyl
      carboxypeptidase specificity.
AB  - Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by mast
      cells. The 2.2 A crystal structure of HC complexed to the peptidyl inhibitor,
      succinyl-Ala-Ala-Pro-Phe-chloromethylketone (CMK), was solved and refined to a
      crystallographic R-factor of 18.4 %. The HC structure exhibits the typical
      folding pattern of a chymotrypsin-like serine proteinase, and shows particularly
      similarity to rat chymase 2 (rat mast cell proteinase II) and human cathepsin G.
      The peptidyl-CMK inhibitor is covalently bound to the active-site residues Ser195
      and His57; the peptidyl moiety juxtaposes the S1 entrance frame segment 214-217
      by forming a short antiparallel beta-sheet. HC is a highly efficient angiotensin
      converting enzyme. Modeling of the chymase-angiotensin I interaction guided by
      the geometry of the bound chloromethylketone inhibitor indicates that the
      extended substrate binding site contains features that may generate the
      dipeptidyl carboxypeptidase-like activity needed for efficient cleavage and
      activation of the hormone. The C-terminal carboxylate group of angiotensin I
      docked into the active-site cleft, with the last two residues extending beyond
      the active site, is perfectly localized to make a favorable hydrogen bond and
      salt bridge with the amide nitrogen of the Lys40-Phe41 peptide bond and with the
      epsilon-ammonium group of the Lys40 side-chain. This amide positioning is unique
      to the chymase-related proteinases, and only chymases from primates possess a Lys
      residue at position 40. Thus, the structure conveniently explains the preferred
      conversion of angiotensin I to angiotensin II by human chymase.

PMID- 9931258
TI  - The structure of the membrane protein squalene-hopene cyclase at 2.0 A
      resolution.
AB  - Squalene cyclases catalyze a cationic cyclization cascade, which is homologous to
      a key step in cholesterol biosynthesis. The structure of the enzyme from
      Alicyclobacillus acidocaldarius has been determined in a new crystal form at 2.0
      A resolution (1 A=0.1 nm) and refined to an R-factor of 15.3 % (Rfree=18.7 %).
      The structure indicates how the initial protonation and the final deprotonation
      of squalene occur and how the transient carbocations are stabilized. The pathways
      of the flexible educt squalene from the membrane interior to the active center
      cavity and of the rigid fused-ring product hopene in the reverse direction are
      discussed. The enzyme contains eight so-called QW-sequence repeats that fortify
      the alpha/alpha-barrels by an intricate interaction network. They are unique to
      the known triterpene cyclases and are presumed to shield these enzymes against
      the released enthalpy of the highly exergonic catalyzed reaction. The enzyme is a
      monotopic membrane protein, the membrane-binding interactions of which are
      described and compared with those of two prostaglandin-H2 synthase isoenzymes,
      the only other structurally characterized proteins of this type. In the crystals
      the membrane-binding regions face each other, suggesting a micelle-type detergent
      structure between them.

PMID- 9931260
TI  - Conformational isomers of a class II MHC-peptide complex in solution.
AB  - A number of kinetic measurements of peptide dissociation from class II MHC
      peptide complexes provide compelling evidence for the existence of conformational
      isomers in solution. There is evidence that T-lymphocytes can distinguish such
      isomers. However, virtually nothing is known about the structure of these
      isomers. Accordingly, we have investigated a water-soluble version of the murine
      class II MHC molecule I-Ek complexed with an antigenic peptide derived from
      pigeon cytochrome c residues 89-104 (PCC) by 19F-NMR. Two fluorine labels were
      placed on the PCC peptide; one fluorine label was placed at a MHC contact site,
      the other at a position involved in T-cell receptor (TCR) recognition.
      Introduction of these labels did not alter the observed kinetics of the PCC/I-Ek
      complex. The NMR data show two conformational isomers of this immunogenic
      complex. The presence of conformational isomers at a TCR contact site suggests
      that these structures may be recognized differently by the TCR. The agreement
      between the dissociation kinetics and the 19F-NMR data demonstrate that kinetic
      heterogeneity is correlated with structural counterparts observed by NMR.
      Dissociations in the presence of dimethyl sulfoxide were used to show that the
      rate of interconversion of these conformational isomers at pH 7.0 is low, with a
      lifetime on the order of hours or more. Modification of a peptide residue of PCC
      occupying the minor MHC binding pocket P6 alters the 19F-NMR spectra of both
      labels. This demonstrates that distant changes of amino acid residues can
      influence the conformation of the whole antigenic peptide inside the MHC binding
      cleft.

PMID- 9931259
TI  - Iron superoxide dismutase from the archaeon Sulfolobus solfataricus: analysis of
      structure and thermostability.
AB  - The crystal structure of superoxide dismutase (SOD) from the hyper thermophile
      Sulfolobus solfataricus has been determined at 2.3 A resolution by molecular
      replacement and refined to a crystallographic R-factor of 16.8 % (Rfree 19.8 %).
      The crystals belong to the space group C2 (a=76.3 A, b=124.3 A, c=60.3 A,
      beta=128.8 degrees) with two identical monomers in the asymmetric unit. The
      monomer has a molecular weight of 24 kDa and consists of 210 amino acid residues
      of which 205 are visible in the electron density map. The overall fold of the
      monomer of S. solfataricus SOD is similar to that of the other known Fe or Mn
      SODs. S. solfataricus SOD forms a very compact tetramer of a type similar to that
      of SOD from the hyperthermophile Aquifex pyrophilus. Both structures show an
      elevated number of inter-subunit ion-pairs compared with the mesophilic SOD from
      Mycobacterium tuberculosis and the thermophilic SOD from Thermus thermophilus.
      However, in contrast to the A. pyrophilus SOD structure, the number of intra
      subunit ion-pairs as well as inter- subunit hydrogen bonds is not higher than in
      the compared mesophilic and thermophilic SOD structures. The electron density
      also revealed an unexpected and unusual covalent modification of a conserved
      tyrosine in the active site. Its involvement in the specific activity of the
      enzyme is discussed.

PMID- 9931261
TI  - Nuclear magnetic resonance and molecular dynamics studies on the interactions of
      the Ras-binding domain of Raf-1 with wild-type and mutant Ras proteins.
AB  - The Ras protein and its homolog, Rap1A, have an identical "effector region"
      (residues 32-40) preceded by Asp30-Glu31 and Glu30-Lys31, respectively. In the
      complex of the "Ras-like" E30D/K31E mutant Rap1A with the Ras-binding domain
      (RBD), residues 51-131 of Raf-1, Glu31 in Rap1A forms a tight salt bridge with
      Lys84 in Raf-1. However, we have recently found that Raf-1 RBD binding of Ras is
      indeed reduced by the E31K mutation, but is not affected by the E31A mutation.
      Here, the "Rap1A-like" D30E/E31K mutant of Ras was prepared and shown to bind the
      Raf-1 RBD less strongly than wild-type Ras, but slightly more tightly than the
      E31K mutant. The backbone 1H, 13C, and 15N magnetic resonances of the Raf-1 RBD
      were assigned in complexes with the wild-type and D30E/E31K mutant Ras proteins
      in the guanosine 5'-O-(beta,gamma-imidotriphosphate)-bound form. The Lys84
      residue in the Raf-1 RBD exhibited a large change in chemical shift upon binding
      wild-type Ras, suggesting that Lys84 interacts with wild-type Ras. The D30E/E31K
      mutant of Ras caused nearly the same perturbations in Raf-1 chemical shifts,
      including that of Lys84. We hypothesized that Glu31 in Ras may not be the major
      salt bridge partner of Lys84 in Raf-1. A molecular dynamics simulation of a model
      structure of the Raf-1 RBD.Ras.GTP complex suggested that Lys84 in Raf-1 might
      instead form a tight salt bridge with Asp33 in Ras. Consistent with this, the
      D33A mutation in Ras greatly reduced its Raf-I RBD binding activity. We conclude
      that the major salt bridge partner of Lys84 in Raf-1 may be Asp33 in Ras.

PMID- 9931262
TI  - Water molecules in the binding cavity of intestinal fatty acid binding protein:
      dynamic characterization by water 17O and 2H magnetic relaxation dispersion.
AB  - The hydration of intestinal fatty acid binding protein (IFABP) in apo-form and
      complexed with palmitate, oleate, and 1-anilino-8-naphthalene sulfonate (ANS) has
      been studied by water 17O and 2H magnetic relaxation dispersion (MRD)
      measurements. These ligands bind in a large internal cavity, displacing most of
      the crystallographically identified cavity water molecules. Unlike most other
      proteins, IFABP gives rise to MRD profiles with two dispersion steps. The low
      frequency dispersion yields a correlation time of 7 ns at 300 K, matching the
      known tumbling time of IFABP. The dispersion amplitude requires only three (apo)
      or four (holo) long-lived and ordered water molecules (residence time 0.01-4
      microseconds at 300 K). Comparison of MRD profiles from the different complexes
      indicates that the displaced cavity water molecules are short-lived. The few long
      lived (>10 ns) water molecules required by the MRD data are tentatively assigned
      to crystallographic hydration sites on the basis of accessibility, positional
      order, and H-bonding. The amplitude of the high-frequency dispersion corresponds
      to 10-20 moderately ordered water molecules, with a correlation time of ca. 1 ns
      that may reflect a transient opening of the cavity required for exchange with
      external water.

PMID- 9931263
TI  - Molecular directionality of beta-chitin biosynthesis.
AB  - The molecular packing in beta-chitin unit cells was experimentally determined by
      a combination of unidirectional degradation by Bacillus circulans chitinase A1
      and microdiffraction electron crystallography using highly crystalline beta
      chitin microfibrils from the protective tubes secreted by Lamellibrachia satsuma.
      The mode of chain packing was found to be identical with that of the previously
      published crystal model for beta-chitin, despite a controversial definition of
      the unit cell parameters. Here, a "parallel-down" packing was determined, where
      the reducing ends of chains point in an opposite direction to the
      crystallographic c-axis. Microdiffraction analyses of nascent beta-chitin
      microfibrils generated from diatom Thalassiosira sp. showed that the c-axis of
      the crystal was directed toward the diatoms, and therefore the reducing end of a
      growing chain pointed away from the locus of biosynthesis. This mechanism agreed
      well with what we found recently in the cellulose biosynthesis system, and
      provides strong evidence that the polymerization by the processive glycosyl
      transferase takes place at the non-reducing end of the growing polysaccharide
      chains.

PMID- 9931264
TI  - Using loop length variants to dissect the folding pathway of a four-helix-bundle
      protein.
AB  - Rop is a four-helix-bundle protein formed by the association of two helix-loop
      helix monomers. The short helix-connecting loop was replaced with a series of
      polyglycine linkers of increasing length. These mutant proteins all appear to
      fold via the same general mechanism as that of the wild-type protein, even at the
      longest loop lengths. Replacement of the wild-type two-residue loop (Asp-Ala)
      with a (Gly-Gly) linker accelerates both unfolding and refolding rates. These
      changes in folding and unfolding kinetics likely indicate an alteration in the
      energy of the transition state. As the length of the glycine linker is further
      increased, the unfolding rate increases while the refolding rates decrease. The
      influence of loop length is not limited to these rates, but also impacts upon the
      stability of the folding intermediate. These dependences underscore the
      importance of loop closure and help refine the model for Rop's folding,
      implicating a dimeric intermediate involving hairpin formation. These
      observations show that loop alteration may be useful as a general technique for
      dissecting protein folding pathways.

PMID- 9931265
TI  - Enzyme specificity under dynamic control: a normal mode analysis of alpha-lytic
      protease.
AB  - We have used alpha-lytic protease as a model system for exploring the
      relationship between the internal dynamics of an enzyme and its substrate
      specificity. The wild-type enzyme is highly specific for small substrates in its
      primary specificity pocket, while the M190A mutant has a much broader
      specificity, efficiently catalyzing cleavage of both large and small substrates.
      Normal modes have been calculated for both the wild-type and the mutant enzyme to
      determine how internal vibrations contribute to these contrasting specificity
      profiles. We find that for the atoms lining the walls of the specificity pocket,
      the wild-type normal modes have a more symmetric character, with the walls
      vibrating in phase, and the size of the pocket remaining relatively fixed. This
      is in agreement with X-ray crystallographic data on conformational substates
      trapped at 120 K. In contrast, we find that in the mutant, the binding pocket
      normal modes have a more antisymmetric character, with the walls vibrating out of
      phase, and the pocket able to expand and contract. These results suggest that the
      internal vibrations of a molecule may play an important role in determining
      substrate binding and specificity. A small change in protein structure can have a
      significant effect on the pattern of molecular vibrations, and thus on enzymatic
      properties, even if the overall amplitudes of the vibrations, as measured by NMR
      relaxation or crystallographic B-factors, remain largely unchanged.

PMID- 9931266
TI  - Domain dislocation: a change of core structure in periplasmic binding proteins in
      their evolutionary history.
AB  - Periplasmic binding proteins (PBPs) serve as receptors for various water-soluble
      ligands in ATP-binding cassette (ABC) transport systems, and form one of the
      largest protein families in eubacterial and archaebacterial genomes. They are
      considered to be derived from a common ancestor, judging from their similarities
      of three-dimensional structure, their mechanism of ligand binding and the operon
      structure of their genes. Nevertheless, there are two types of topological
      arrangements of the central beta-sheets in their core structures. It follows that
      there must have been differentiation in the core structure, which we call "domain
      dislocation", in the course of evolution of the PBP family. To find a clue as to
      when the domain dislocation occurred, we constructed phylogenetic trees for PBPs
      based on their amino acid sequences and three-dimensional structures,
      respectively. The trees show that the proteins of each type clearly cluster
      together, strongly indicating that the change in the core structure occurred only
      once in the evolution of PBPs. We also constructed a phylogenetic tree for the
      ABC proteins that are encoded by the same operon of their partner PBP, and
      obtained the same result. Based on the phylogenetic relationship and comparison
      of the topological arrangements of PBPs, we obtained a reasonable genealogical
      chart of structural changes in the PBP family. The present analysis shows that
      the unidirectional change of protein evolution is clearly deduced at the level of
      protein three-dimensional structure rather than the level of amino acid sequence.

PMID- 9931267
TI  - Non-proline cis peptide bonds in proteins.
AB  - In a non-redundant set of 571 proteins from the Brookhaven Protein Data Base, a
      total of 43 non-proline cis peptide bonds were identified. Average geometrical
      parameters of the well-defined cis peptide bonds in proteins determined at high
      resolution show that some parameters, most notably the bond angle at the amide
      bond nitrogen, deviate significantly from the corresponding one in the trans
      conformation. Since the same feature was observed in cis amide bonds in small
      molecule structures found in the Cambridge Structural Data Base, a new set of
      parameters for the refinement of protein structures containing non-Pro cis
      peptide bonds is proposed.A striking preference was observed for main-chain
      dihedral angles of the residues involved in cis peptide bonds. All residues N
      terminal and most residues C-terminal to a non-Pro cis peptide bond (except Gly)
      are located in the beta-region of a phi/psi plot. Also, all of the few C-terminal
      residues (except Gly) located in the alpha-region of the phi/psi plot constitute
      the start of an alpha-helix in the respective structure. In the majority of
      cases, an intimate side-chain/side-chain interaction was observed between the
      flanking residues, often involving aromatic side-chains. Interestingly, most of
      the cases found occur in functionally important regions such as close to the
      active site of proteins. It is intriguing that many of the proteins containing
      non-proline cis peptide bonds are carbohydrate-binding or processing proteins.
      The occurrence of these unusual peptide bonds is significantly more frequent in
      structures determined at high resolution than in structures determined at medium
      and low resolution, suggesting that these bonds may be more abundant than
      previously thought. On the basis of our experience with the structure
      determination of coagulation factor XIII, we developed an algorithm for the
      identification of possibly overlooked cis peptide bonds that exploits the
      deviations of geometrical parameters from ideality. A few likely candidates based
      on our algorithm have been identified and are discussed.

PMID- 9931268
TI  - Cortical surface-based analysis. I. Segmentation and surface reconstruction.
AB  - Several properties of the cerebral cortex, including its columnar and laminar
      organization, as well as the topographic organization of cortical areas, can only
      be properly understood in the context of the intrinsic two-dimensional structure
      of the cortical surface. In order to study such cortical properties in humans, it
      is necessary to obtain an accurate and explicit representation of the cortical
      surface in individual subjects. Here we describe a set of automated procedures
      for obtaining accurate reconstructions of the cortical surface, which have been
      applied to data from more than 100 subjects, requiring little or no manual
      intervention. Automated routines for unfolding and flattening the cortical
      surface are described in a companion paper. These procedures allow for the
      routine use of cortical surface-based analysis and visualization methods in
      functional brain imaging.

PMID- 9931269
TI  - Cortical surface-based analysis. II: Inflation, flattening, and a surface-based
      coordinate system.
AB  - The surface of the human cerebral cortex is a highly folded sheet with the
      majority of its surface area buried within folds. As such, it is a difficult
      domain for computational as well as visualization purposes. We have therefore
      designed a set of procedures for modifying the representation of the cortical
      surface to (i) inflate it so that activity buried inside sulci may be visualized,
      (ii) cut and flatten an entire hemisphere, and (iii) transform a hemisphere into
      a simple parameterizable surface such as a sphere for the purpose of establishing
      a surface-based coordinate system.

PMID- 9931270
TI  - Ultrastructure of familial amyloid polyneuropathy amyloid fibrils: examination
      with high-resolution electron microscopy.
AB  - The ultrastructure of familial amyloid polyneuropathy (FAP) amyloid fibrils was
      examined with high-resolution electron microscopy and immunolabeling. Sural nerve
      biopsies from FAP (Met 30) patients as well as control tissues were prepared for
      thin-section observations. Extracellular spaces in the vicinity of myelinated and
      unmyelinated peripheral nerves were found to be filled with amyloid fibrils as
      well as with deposits of an "amorphous" material. The fibril was composed of a
      surface layer and a core. The surface layer was made up of heparan sulfate
      proteoglycan and was externally associated with a loose assembly of 0.5- to 1-nm
      wide filaments. The core was a microfibril-like structure in which amyloid P
      component was enclosed in a tight helical structure by chondroitin sulfate
      proteoglycan. Immunogold labeling showed that the peripheral fine filaments were
      composed of transthyretin. The dimensions of the transthyretin filament suggest
      that its basic unit is a modified monomer. The deposited amorphous material was a
      mixture of individual components of the fibril. These results suggest that the
      main body of FAP amyloid fibrils is similar to that of recently observed fibrils
      of experimental murine AA and hemodialysis-associated amyloid as well as of
      connective tissue microfibrils. The differences in the fibrils of these various
      types of amyloid are in the peripheral filaments which are composed of a protein
      specific to each type of amyloid.

PMID- 9931272
TI  - Molecular imaging of halocynthia papillosa cellulose 
AB  - The molecular organization of cellulose Ibeta microfibrils in the tunic of
      Halocynthia papillosa was analyzed by high-resolution cryoelectron microscopy on
      ultrathin cross sections of artificially highly oriented microfibrils. The
      arrangement of cellulose chains intersected by the 0.6-, 0.53-, and 0.39-nm
      equatorial lattice planes was clearly imaged over the whole area of a
      parallelogram-shaped cross section of a microfibril. One, edge of the
      parallelogram was parallel to the 0.6-nm lattice plane, while the other did not
      correspond to a crystallographic plane. Such organization is distinct from
      previous findings on algal cellulose Ialpha-rich microfibrils, which have an
      almost square cross section bounded by both 0.6- and 0.53-nm crystallographic
      planes. A tentative model for microfibril formation is proposed by introducing a
      two-step biocrystallization mechanism: the formation of molecular sheets spaced
      by 0.53 nm between adjacent molecules, followed by self-deposition of these
      sheets by hydrogen bonding between them. Copyright 1998 Academic Press.

PMID- 9931271
TI  - Reorganization of stress fiber-like structures in spreading platelets during
      surface activation.
AB  - Alpha-Actinin and myosin were associated into reorganized actin cable networks
      and partly formed stress fiber-like structures in platelets during surface
      activation. Double-label immunofluorescence staining using antibodies against
      alpha-actinin and platelet myosin heavy chain (MHC) showed that alpha-actinin and
      myosin were colocalized in the cell center at the early stage of activation and
      dynamically redistributed with shape change. In the later stage, two proteins
      were colocalized around the granulomeres. alpha-Actinin was also seen beneath the
      surface membrane while myosin was not. Occasionally, both proteins were
      segregated, revealed granular staining in the cell body of flattened platelets
      and often aligned irregular alternate arrangement in the actin cables.
      Immunoelectron microscopy (immunogold) employing antibodies against MHC and
      myosin light chain (MLC) demonstrated that myosin, associated with actin
      cytoskeleton was precisely filamentous (328 nm in average length, 15 nm in width)
      and bipolar with a central bare zone, since MLCs were located at both ends.
      Myosin formed a cluster composed of several filaments with repeating alignment,
      suggesting each cluster corresponded to the granular staining pattern of
      immunofluorescence. These observations indicated that the organization of alpha
      actinin and myosin in actin cables in activated platelets resembled that in
      stress fibers in various cultured cells.

PMID- 9931273
TI  - The nuclear basket of the nuclear pore complex is part of a higher-order
      filamentous network that is related to chromatin.
AB  - We have achieved well-preserved nuclear basket structures in amphibian nuclear
      envelope spreads dried by the critical point method after tannic acid fixation,
      and we have compared these images with those obtained from conventional sections
      of amphibian oocyte nuclei. In cross sections, bundles of filaments from adjacent
      nuclear pore complexes were interconnected at regular distances, building up a
      higher-order network. Sometimes these bundles were observed to extend inward to
      amplified nucleoli located near the nuclear envelope. Furthermore, immunoelectron
      analysis indicated that DNA and histones were localized at these intranuclear
      filaments, suggesting a close relationship between chromatin and nuclear pore
      complexes. A model is proposed by which the intranuclear filaments associated
      with adjacent nuclear pore complexes create a regular higher-order network, which
      extends into the nucleus.

PMID- 9931274
TI  - High-voltage electron microscopy and 3-D reconstruction of solitary chemosensory
      cells in the anterior dorsal fin of the Gadid fish Ciliata mustela (Teleostei).
AB  - Solitary chemosensory cells (SCCs) are secondary sensory cells present in the
      epidermis of most primary aquatic vertebrates. In rocklings, the epidermis of the
      anterior dorsal fin (ADF) contains approximately 5 million SCCs. High-voltage
      electron microscopy and three-dimensional reconstructions from serial sections
      were used to examine the ultrastructure, arrangement, and synaptic contacts of
      the SCCs in the rockling ADF. Approximately 15% of all cells in the fin ray
      epidermis are SCCs, which occupy roughly 30% of the epidermal volume. These
      spindle-shaped cells are 25-30 microm long and up to 10 microm wide and terminate
      apically in a microvillus protruding 2-5 microm above the epidermal surface. SCCs
      contain abundant endoplasmic reticulum and a large Golgi apparatus in their
      proximal regions. The distal parts of SCCs contain characteristic vesicles,
      elongate mitochondria, and longitudinal strands of intermediate filaments.
      Synapses between SCCs and nerves resemble those found in teleost taste buds. One
      to four synaptic contacts per SCC were found. We hypothesize that the apparent
      secretory activity of the SCCs serves to replenish the apical membrane and mucus.
      Furthermore, parallel sampling of several hundred SCCs by single nerve fibers may
      serve low-threshold detection rather than stimulus localization.

PMID- 9931275
TI  - Structure of the human cytomegalovirus B capsid by electron cryomicroscopy and
      image reconstruction.
AB  - The three-dimensional structure of B capsids of the beta-herpesvirus human
      cytomegalovirus (HCMV) was investigated at a resolution of 3.5 nm from electron
      cryomicrographs by image processing and compared with the structure obtained for
      the alpha-herpesvirus herpes simplex virus type 1 (HSV-1). The main architectural
      features of the HSV-1 and HCMV capsids are similar: the T = 16 icosahedral
      lattice consists of 162 capsomers, composed of two distinct morphological units,
      12 pentamers and 150 hexamers, with triplex structures linking adjacent capsomers
      at positions of local threefold symmetry. The main differences in the HSV-1 and
      HCMV capsids are found in the diameter of the capsids (125 and 130 nm,
      respectively); the hexamer spacing and relative tilt (center-to-center hexon
      spacing at outer, edge, 17.9 and 15.8 nm, respectively); the morphology of the
      tips of the hexons (similar in length but 33% thinner in HCMV); and the average
      diameter of the scaffold (44 and 76 nm, respectively). By analogy with HSV-1, the
      mass on the HCMV hexon tip is attributed to the smallest capsid protein (HCMV
      gene UL48/49). The differences in capsid structure are discussed in relation to
      the ability of the HCMV structure to package a genome some 60% larger than that
      of HSV-1.

PMID- 9931276
TI  - Minimal radius of curvature of lipid bilayers in the gel phase state corresponds
      to the dimension of biomembrane structures "caveolae".
AB  - Caveolae are membrane invaginations with a radius of curvature in the range of 40
      nm for the bulb; 10-15 nm is the minimal radius for lipid bilayers in the liquid
      crystalline Lalpha (liquid-disordered: ld) phase state. A minimal radius of 20-30
      nm could be detected for the gel phase state by analysis of convex-concave
      bilayer deformations. Circular protrusions with a diameter in the range of only
      about 40 nm are closed by a flat lid, and those with diameters of 60 nm or more
      are closed by hemispherical caps. These structures are found primarily in
      phosphatidylcholine/sterol mixtures, where the gel phase state "liquid ordered"
      (lo) has been introduced. As a further example the mixture of
      dimyristoylphosphatidylcholine (DMPC) with an unusual sterol (diflucortolon-21
      valerat) is presented. In the usual hydration at temperatures above the phase
      transition the deformation requires an incubation at 4 degrees C for several
      weeks or months to form. Using a low temperature hydration procedure (at 4
      degrees C), surprisingly bilayers of pure DMPC and DPPC
      (dipalmitoylphosphatidylcholine) are found to deform in the same convex-concave
      manner, and this takes place within hours and days. The dependence on hydration
      protocol is also observed for formation of a sponge-like bilayer network with 30
      35 nm radius of curvature in brain sphingomyelin and its mixtures with
      cholesterol. Caveolae are microdomains enriched in cholesterol and sphingomyelin
      and are simultaneously discussed to be in the lo state. Direct evidence by
      investigation of bilayers formed by the lipids isolated from caveolae is still
      lacking, but structures similar to caveolae which are in the gel phase state
      (very probably the lo state) are also formed by lipids extracted from bacterial
      membranes. A further analogy exists because both natural lipid mixtures (brain
      sphingomyelin and bacterial lipids) transform during heating from the curved
      bilayer structures into microvesicles above the phase transition. Internalization
      of caveolae is a process of vesicle formation.

PMID- 9931277
TI  - In vitro amyloid fibril formation by synthetic peptides corresponding to the
      amino terminus of apoSAA isoforms from amyloid-susceptible and amyloid-resistant
      mice.
AB  - Specific proteins of the apolipoprotein serum amyloid (apoSAA) family that are
      synthesized in large quantities during the acute, early phase of inflammation can
      serve as the proteinaceous precursors for amyloid fibrils. To model
      fibrillogenesis in such inflammatory diseases, we have used electron microscopy
      and X-ray diffraction to examine the structures formed by synthetic peptides
      corresponding in sequence to the 11 amino-terminal amino acids of murine apoSAA1,
      apoSAAcej, and apoSAA2 and to the 15 amino-terminal amino acids of apoSAA2. This
      region is reported to be the major fibrillogenic determinant of apoSAA isoforms.
      Both in 1 mM Tris buffer and in 35% acetonitrile, 0.1% trifluoracetic acid
      (ACN/TFA), all of the peptides formed macromolecular assemblies consisting of
      twisted, approximately 40- to 60-A-thick ribbons, which varied in width from
      around 40-70 A (for 11-mer apoSAA2 in Tris) up to 900 A (for the other peptides).
      X-ray diffraction patterns recorded from lyophilized peptides, vapor-hydrated
      samples, and solubilized/dried samples showed hydrogen bonding and intersheet
      reflections typical of a beta-pleated sheet conformation. The coherent lengths
      measured from the breadths of the X-ray reflections indicated that with hydration
      the growth of the assemblies in the intersheet stacking direction was comparable
      to that in the hydrogen-bonding direction, and analysis of oriented samples
      showed that the beta-strands were oriented perpendicular to both the long axis
      and the face of the assemblies. These X-ray results are consistent with the
      ribbon- or plate-like morphology of the individual aggregates and emphasize the
      polymorphic nature of amyloidogenic peptides. Our findings demonstrate that X-ray
      diffraction measurements on vapor-hydrated or solubilized/dried versus
      lyophilized, amyloidogenic peptides are a good indicator of their fibrillogenic
      potential. For example, from the highest to the lowest potential, the peptides
      examined here were ranked as: Abeta1-28 > Abeta1-40 > apoSAA1 approximately
      apoSAAcej > apoSAA2 > Abeta17-42. Experiments in which the three different 11-mer
      apoSAA isoforms were solubilized in ACN/TFA and then combined as binary mixtures
      showed that the ribbon morphology was not affected but that the extent of
      hydrogen bonding in the assemblies was substantially reduced. Our observations on
      the in vitro assembly of apoSAA analogs emphasize that amyloid fibril formation
      and morphology depend on primary sequence, length of polypeptide chain, the
      presence of additional fibrillogenic polypeptides, and solvent conditions.

PMID- 9931278
TI  - Crystallization and preliminary X-ray crystallographic study of a 23S rRNA
      binding domain of the ribosomal protein L2 from Bacillus stearothermophilus.
AB  - Ribosomal protein L2 from Bacillus stearothermophilus, a single polypeptide chain
      with 275 amino acid residues, is a primary 23S rRNA-binding protein in the large
      ribosomal subunit. Crystals of a 23S rRNA binding domain (BstL2-RBD: positions 60
      201) of the ribosomal protein L2 from B. stearothermophilus overexpressed in
      Escherichia coli have been grown in 0.1 M MES (pH 6.5) containing 15%
      polyethylene glycol 20 000. The crystals diffract to 2.3-A resolution on a
      synchrotron X-ray source. The crystal belongs to the space group P1 and the unit
      cell axes are a = 28.05, b = 36.20, c = 69.74 A, alpha = 99.58 degrees, beta =
      95.86 degrees, and gamma = 102.62 degrees. There are two molecules of the BstL2
      RBD in the asymmetric unit.

PMID- 9931279
TI  - Methyl mercury-induced autoimmunity in mice.
AB  - Female SJL/N, A.SW, B10.S (H-2s), BALB/C, DBA/2 (H-2d), A.TL and B10. TL (H-2t1)
      mice were treated with sc injections of 1.0 mg CH3HgCl/kg body weight every third
      day for 4 weeks. Controls were given sterile, isotonic NaCl. CH3HgCl (MeHg)
      induced in SJL, A.SW and B10.S mice antinucleolar antibodies (ANoA) targeting the
      nucleolar 34-kDa protein fibrillarin. The susceptibility to develop ANoA in
      response to MeHg was linked to the mouse major histocompatibility complex (H-2),
      since H-2s but not H-2t1 mice sharing background (non-H-2) genes developed ANoA.
      However, the background genes decided the strength of the ANoA response in the
      susceptible H-2s mice, and the ANoA titer was in the order: A.SW > SJL > B10.S.
      Although MeHg as well as inorganic mercury induced ANoA, the two forms of mercury
      differed both quantitatively and qualitatively in their effect on the immune
      system. MeHg induced in H-2s mice a weaker general (polyclonal) and specific
      (ANoA) B-cell response than HgCl2, probably due to weaker activation of Th2 cells
      with lower IL-4 production, as indicated by the minimal increase in serum IgE.
      The A. TL strain with a susceptible genetic background, but a H-2 haplotype
      resistant to HgCl2, responded to MeHg with a modest polyclonal B-cell response
      dominated by Th1-associated Ig isotypes. H-2s mice treated with MeHg showed in
      contrast to HgCl2-treated mice no systemic immune-complex (IC) deposits, which
      may be due to the weaker immune activation after MeHg treatment. The increase in
      serum IgE concentration and ANoA titer 2-6 weeks after stopping treatment with
      MeHg is identical to reactions during the first 2-3 weeks of HgCl2 treatment.
      Therefore, demethylation of MeHg probably increased the concentration of
      inorganic mercury in the body sufficiently to reactivate the immune system. This
      reactivation indicated that genetically susceptible mice are not resistant to
      challenge with mercury, making them distinctly different from rats.

PMID- 9931280
TI  - Cadmium binding and sodium-dependent solute transport in renal brush-border
      membrane vesicles.
AB  - Exposure to cadmium (Cd) impairs renal transport systems for glucose, amino
      acids, phosphate, and dicarboxylates. To investigate if these changes are
      directly related to a Cd binding to the renal brush-border membrane, Cd binding
      and the Na+-dependent uptakes of d-glucose, l-alanine, phosphate, and succinate
      were determined in rat renal brush-border membrane vesicles (BBMV) exposed to
      CdCl2. Cd uptake by BBMV showed time and concentration dependence. Changes in
      medium osmolality had no effect on Cd uptake, indicating that the process
      primarily involves binding of Cd to the membrane. Scatchard analysis indicated
      the presence of two types of Cd binding sites, differing in affinity and number.
      Increasing the medium Cd concentration from 50 to 200 microM resulted in a
      progressive increase in Cd binding to the membrane and decrease in Na+-dependent
      transport of d-glucose, l-alanine, inorganic phosphate, and succinate. In all
      cases, the inhibition of transport was directly proportional to the total amount
      of Cd binding to the membrane. These results suggest that, during chronic
      exposure to Cd, free Cd ions liberated in renal tubular cells may directly
      interact with brush-border membranes and impair Na+-dependent solute transports.

PMID- 9931281
TI  - Activation of NF-kappaB in normal rat kidney epithelial (NRK52E) cells is
      mediated via a redox-insensitive, calcium-dependent pathway.
AB  - Renal tubular epithelial cells are largely resistant to oxidant-induced injury
      despite their capacity to accumulate relatively high concentrations of
      potentially damaging prooxidant and thiol-depleting agents. In the present study,
      we tested the hypothesis that such resistance may be attributable to a lack or
      deficiency of signaling transduction pathways through which reactive oxidants
      have been shown to promote the activation of NF-kappaB, a transcriptional factor
      that is known to mediate the inducible expression of a wide variety of genes that
      are involved in inflammatory and other cytotoxic reactions in numerous cell
      types. NF-kappaB was found to be readily activated following exposure of cultured
      normal rat kidney epithelial (NRK52E) cells to bacterial lipopolysaccharide
      (LPS). However, in contrast to findings with many other cell types, the
      activation of NF-kappaB by LPS was not substantially altered either by
      pretreatment of cells with the thiol antioxidant, N-acetylcysteine, or by
      glutathione (GSH) depletion. Moreover, reactive oxidants and oxidative stress
      generating chemicals were completely without effect with respect to NF-kappaB
      activation in NRK52E cells, even following GSH depletion. In contrast, LPS
      activation of NF-kappaB was substantially attenuated by the intracellular Ca2+
      chelator, Quin 2AM, and by the Ca-channel inhibitor, ruthenium red. Moreover,
      thapsigargin, a Ca-ATPase inhibitor, promoted NF-kappaB activation comparable to
      that observed by LPS. Additionally, staurosporine, a Ca-dependent protein kinase
      C inhibitor, substantially decreased LPS-mediated NF-kappaB activation. These
      results demonstrate that the LPS-inducible expression of NF-kappaB in renal
      epithelial cells, in contrast to many other cell types, is not responsive to
      oxidative stress and is regulated, at least in part, by redox-insensitive
      modulation of intracellular calcium levels. These findings provide a basis for
      the highly tissue-specific expression and function of NF-kappaB in kidney
      epithelial cells, which may underlie their resistance to oxidant-mediated
      cytotoxicity.

PMID- 9931282
TI  - Molecular genotoxicity profiles of apoptosis-inducing vanadocene complexes.
AB  - Metallocene complexes containing vanadium induce apoptosis in human cancer cells
      by an as yet unknown mechanism and may therefore be useful as a new class of
      cytotoxic anticancer drugs. Ultrastructural studies showing the formation of
      metallocene-DNA complexes prompted the hypothesis that their mechanism of action
      may resemble the DNA damage induced by cisplatin. Molecular genotoxicity testing
      provides insights into the mechanisms of action of new chemotherapeutic agents.
      Therefore, we determined the effects of three cytotoxic vanadocene complexes,
      vanadocene dichloride, vanadocene dithiocyanate, and vanadocene dioxycyanate, on
      genomic stability using the yeast DEL recombination assay and transcriptional
      activation of genotoxic stress-specific promoters in human HepG2 cells using the
      CAT-Tox(L) assay. Cisplatin caused an 11-fold increase of recombination frequency
      in yeast and induced transcriptional activation of the DNA damage-associated
      promoters such as the minimum promoter containing p53 response elements and the
      GADD45 promoter in addition to activating the promoters for c-fos, heat shock
      protein 70, metallothionine IIa, and the minimum promoter containing nuclear
      factor kappa(kappa)B response elements. In contrast to cisplatin, vanadocene
      complexes did not increase the DEL recombination frequency in yeast nor did they
      activate any of the DNA damage-associated promoters in HepG2 cells. Vanadocene
      complexes triggered activation of the c-fos promoter without affecting the
      minimum promoter containing p53 response elements or the GADD45 promoter. These
      results indicate that the apoptotic signal of vanadocene complexes is not
      triggered by primary DNA damage and it does not require p53 induction, thereby
      disproving the hypothesis that it mechanistically resembles the cytotoxic action
      of cisplatin.

PMID- 9931283
TI  - Effects of the antiestrogenic environmental pollutant 3,3',4,4', 5
      pentachlorobiphenyl (PCB #126) in rat bone and uterus: diverging effects in
      ovariectomized and intact animals.
AB  - The purpose of this study was to compare effects on rat bone and uterus of
      estrogen depletion and exposure to the coplanar PCB-congener 3,3',4,4',5
      pentachlorobiphenyl (PCB #126) which exhibits anti-estrogenic properties. Half of
      the rats were ovariectomized (n = 20) and the other half were sham-operated. Ten
      of the ovariectomized rats and ten of the sham operated were exposed to PCB #126
      (ip injections) for 3 months (total dose: 384 microgram/kg body wt). The
      remaining control rats were injected with corn oil (vehicle). The rats were
      killed and the tibiae and uteri were dissected. The left tibia was used for
      measurements of weight, length, and bone mineral density and the right for
      histomorphometrical analysis. The uteri were analyzed with respect to estrogen
      receptor content. PCB #126 exposure did not affect bone mineral density or
      trabecular bone volume of tibia in sham-operated rats. In ovariectomized rats PCB
      #126 exposure resulted in a decreased length and an increased bone mineral
      density of tibia. An obvious PCB #126 induced increase in osteoid surface was
      observed in sham-operated rats. The cortical thickness and the organic content of
      the tibia were also increased in these rats. In estrogen deprived tissue like the
      uteri of ovariectomized rats, PCB #126 showed weak estrogen agonistic activity.
      The observed effects of PCB #126 on bone and uterine tissues differed between
      ovariectomized and sham-operated rats.

PMID- 9931284
TI  - DNA-Protein crosslinks induced by nickel compounds in isolated rat renal cortical
      cells and its antagonism by specific amino acids and magnesium ion.
AB  - Suspensions of isolated renal cortical cells in modified Krebs-Henseleit buffer
      (pH 7.4) were incubated with nickel chloride, nickel acetate, nickel sulfate, and
      nickel subsulfide (0-2 mM) at 37 degreesC for 2 h. A significant increase (63%)
      in DNA-protein crosslinks was observed at 2 mM nickel sulfate, whereas nickel
      subsulfide induced a significant increase in such crosslinks beginning at 0.5 mM
      concentration and a maximum increase of 200% of the control value reached at 2 mM
      concentration. No significant reduction in viability of renal cortical cells (as
      measured by trypan blue exclusion) was observed due to these nickel compounds at
      any concentration used. In the second series of experiments, coincubation of
      nickel subsulfide (2 mM) with l-histidine (8 or 16 mM), l-cysteine (4 or 8 mM),
      or l-aspartic acid (8 or 24 mM) significantly reduced the DNA-protein crosslinks
      induced by 2 mM nickel subsulfide. Similarly Mg2+ (24 mM), but not Ca2+ (24 mM),
      was able to antagonize nickel subsulfide-induced increase in DNA-protein
      crosslinks. High extracellular levels of Mg2+ and these amino acids significantly
      decreased the accumulation of Ni2+ from nickel subsulfide in renal cortical
      cells. Furthermore, these amino acids at high concentrations significantly
      inhibited the binding of Ni2+ from nickel subsulfide to deproteinized DNA from
      renal cortical cells, whereas such inhibition due to Mg2+ was close to
      significant (0.1 > p > 0.05). In vitro exposures of renal cortical cells to
      nickel subsulfide (0-2 mM) increased the formation of reactive oxygen species in
      concentration-dependent manner. Furthermore, coincubation of 2 mM nickel
      subsulfide with either catalase, dimethylthiourea, mannitol, or vitamin C at 37
      degreesC for 2 h resulted in a significant decrease of nickel subsulfide-induced
      formation of DNA-protein crosslinks, suggesting that nickel subsulfide-induced
      DNA-protein crosslink formation in isolated rat renal cortical cells is caused by
      the formation of reactive oxygen species. The potent protective effects of these
      specific amino acids and Mg2+ against nickel subsulfide-induced DNA-protein
      crosslink formation in isolated renal cortical cells are due to reduction of
      cellular uptake of Ni2+ and inhibition of the binding of Ni2+ to deproteinized
      DNA.

PMID- 9931285
TI  - Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and
      renal toxicity and protection by antioxidants.
AB  - The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention
      by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley
      rats were injected sc with 5 micromol CdCl2/kg/day, 5 times a week, for up to 22
      weeks. Serum alanine amino transferase and lactate dehydrogenase activities were
      elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal
      toxicity, indicated by elevation in urinary lactate dehydrogenase activity and
      protein, was also observed around this time. Chronic Cd administration resulted
      in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite
      of this, lipid peroxidation increased in both tissues, particularly during the
      second half of the Cd exposure period. Depletion of glutathione following
      buthionine sulfoximine administration at the end of Week 5, or inhibition of
      catalase by aminotriazole at the end of Week 7, resulted in the development of
      acute nephrotoxicity within 6 h. Coadministration of antioxidants, N
      acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd,
      starting from the early phases of Cd exposure, controlled Cd-induced lipid
      peroxidation and protected the animals against hepatic as well as renal toxicity.
      A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing
      glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic
      Cd nephrotoxicity. In conclusion, oxidative stress appears to play a major role
      in chronic Cd-induced hepatic and renal toxicity since inhibition of components
      of the antioxidant defense system accelerated and administration of antioxidants
      protected against Cd toxicity.

PMID- 9931286
TI  - Physiologically based pharmacokinetic modeling of inhaled trichloroethylene and
      its oxidative metabolites in B6C3F1 mice.
AB  - A physiologically based pharmacokinetic (PBPK) model for inhaled
      trichloroethylene (TCE) was developed for B6C3F1 mice. Submodels described four
      P450-mediated metabolites of TCE, which included chloral hydrate (CH), free and
      glucuronide-bound trichloroethanol (TCOH-f and TCOH-b), trichloroacetic acid
      (TCA), and dichloroacetic acid (DCA). Inhalation time course studies were carried
      out for calibration of the model by exposing mice to TCE vapor concentrations of
      either 100 or 600 ppm for 4 h. At several time points, mice were euthanized and
      blood, liver, kidney, lung, and fat were collected and analyzed for TCE and its
      oxidative metabolites. Peak blood TCE concentrations were 0.86 and 7.32
      microgram/mL, respectively, in mice exposed to 100 and 600 ppm TCE. The model
      overpredicted the mixed venous blood and tissue concentrations of TCE for mice of
      both exposure groups. Fractional absorption of inhaled TCE was proposed to
      explain the discrepancy between the model predictions and the TCE blood time
      course data. When fractional absorption (53%) of inhaled TCE was incorporated
      into the model, a comprehensive description of the uptake, distribution, and
      clearance of TCE in the blood was obtained. Fractional uptake of inhaled TCE was
      further verified by collecting TCE in exhaled breath following a 4-h constant
      concentration exposure to TCE and validation was provided by testing the model
      against TCE blood concentrations from an independent data set. The submodels
      adequately simulated the distribution and clearance kinetics of CH and TCOH-f in
      blood and the lungs, TCOH-b in the blood, and TCA and DCA, which were
      respectively detected for up to 43 and 14 h postexposure in blood and livers of
      mice exposed to 600 ppm TCE. This is the first extensive tissue time course study
      of the major metabolites of TCE following an inhalation exposure to TCE and the
      PBPK model predictions were in good general agreement with the observed kinetics
      of the oxidative metabolites formed in mice exposed to TCE concentrations of 100
      and 600 ppm.

PMID- 9931287
TI  - Characterization of the dose-response of CYP1B1, CYP1A1, and CYP1A2 in the liver
      of female Sprague-Dawley rats following chronic exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - One of the current knowledge gaps in the evaluation of risk for human exposure to
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the relationship between gene
      expression induced by TCDDmore complex biological responses such as altered
      growth, differentiation, and neoplasia. This study investigates the dose
      dependent expression of CYP1A1, CYP1A2,CYP1B1 in the livers of female Sprague
      Dawley rats chronically exposed to TCDD. Animals were treated biweekly for 30
      weeks with daily averaged doses of 0 to 125 ng TCDD/kg/day. Immunoblot analysis
      showed that protein levels for CYP1B1, CYP1A1, CYP1A2 exhibited a dose-dependent
      induction by TCDD. However, CYP1A1 and CYP1A2 protein levels were approximately
      100-fold higher than CYP1B1, which could not be detected by either immunoblot
      analysis or immunohistochemistry in the livers of rats treated with TCDD for 30
      weeks at a dose-equivalent less than 35.7 ng/kg/day. In control animals,
      CYP1A1CYP1A2 RNA levels, measured by quantitative RT-PCR, were 1100-15,000-fold
      higher than that of CYP1B1, respectively. TCDD induced CYP1B1 RNA levels at all
      doses, although absolute TCDD-induced levels of CYP1A1CYP1A2 at the highest dose
      (125 ng/kg/day) were more than 40-fold higher than that of CYP1B1. While the
      liver concentration of TCDD required for half-maximal induction of CYP1A1,
      CYP1A2,CYP1B1 RNA levels was similar, the shaping parameter (Hill coefficient) of
      the dose-response curve for CYP1B1 was significantly higher than that for CYP1A1
      or CYP1A2. The low level of TCDD-induced CYP1B1 expression in the liver relative
      to that of the CYP1A1CYP1A2 suggest that, if CYP1B1 is involved in TCDD-induced
      hepatocarcinogenesis, its endogenous function is likely to be uniquenot
      overlapping with that of CYP1A1 or CYP1A2.

PMID- 9931290
TI  - Chemical index for volume 154 

PMID- 9931288
TI  - Arsenite methylation by methylvitamin B12 and glutathione does not require an
      enzyme.
AB  - Although inorganic arsenic is methylated enzymatically by arsenic
      methyltransferases, which have been found in many mammalian livers, the detection
      of such enzymes has not been successful in surgically removed human livers.
      Results of the present experiments demonstrated that methylvitamin B12
      (methylcobalamin, CH3B12) in the presence of thiols and inorganic arsenite can
      produce, in vitro, substantial amounts of monomethylarsonic acid (MMA) and small
      amounts of dimethylarsinic acid (DMA) in the absence of enzymes. Furthermore,
      this nonenzymatic methylation of inorganic arsenite by CH3B12 was increased
      substantially by the presence of dimercaptopropanesulfonate (DMPS) and/or sodium
      selenite. The actions of DMPS and selenite together were additive. The
      methylation by CH3B12 was neither inhibited nor stimulated by human liver
      cytosol. Since the amount of MMA produced by the in vitro system described in
      this study was not small, these results emphasize the need for a properly
      designed nutritional study in humans exposed to inorganic arsenic as to the
      relationship between vitamin B12, selenium, and the metabolism of carcinogenic
      inorganic arsenic.

PMID- 9931293
TI  - Activity of human 11-cis-retinol dehydrogenase (Rdh5) with steroids and retinoids
      and expression of its mRNA in extra-ocular human tissue.
AB  - This report describes the activity of recombinant human Rdh5 (11-cis-retinol
      dehydrogenase) with steroids and retinoids and expression of the Rdh5 mRNA in
      extra-ocular human tissue. The data show that Rdh5 catalyses 9-cis-retinol
      metabolism equally efficiently as 11-cis-retinol metabolism and recognizes 5alpha
      androstan-3alpha,17beta-diol and androsterone as substrates (3alpha
      hydroxysteroid dehydrogenase activity), but not testosterone,
      dihydrotestosterone, oestradiol and corticosterone (lack of 17beta-hydroxysteroid
      and 11beta-hydroxysteroid dehydrogenase activities). Rdh5 mRNA expression was
      widespread in extra-ocular tissues with human liver (100% relative expression in
      extra-ocular tissues only) and mammary gland (97% relative to liver) showing the
      most intense signals. Other noteworthy relatively intense expression sites
      included colon (45%), thymus (43%), small intestine (39%), kidney (37%), bladder
      (29%), pancreas and spleen (28% each), heart (26%), uterus and ovary (25% each),
      testis (22%) and spinal cord (24%). Human fetal tissues also expressed Rdh5 with
      fetal liver showing the most intense expression among the fetal tissues (20%).
      Considered along with the identical nucleotide sequences in the untranslated
      regions of human Rdh5 and human 9-cis-retinol dehydrogenase cDNAs and the nearly
      identical nucleotide sequences overall (99% identity), the current results
      suggest that the two cDNAs represent a single gene product.

PMID- 9931291
TI  - Recognition of DNA alterations by the mismatch repair system.
AB  - Misincorporation of non-complementary bases by DNA polymerases is a major source
      of the occurrence of promutagenic base-pairing errors during DNA replication or
      repair. Base-base mismatches or loops of extra bases can arise which, if left
      unrepaired, will generate point or frameshift mutations respectively. To
      counteract this mutagenic potential, organisms have developed a number of
      elaborate surveillance and repair strategies which co-operate to maintain the
      integrity of their genomes. An important replication-associated correction
      function is provided by the post-replicative mismatch repair system. This system
      is highly conserved among species and appears to be the major pathway for strand
      specific elimination of base-base mispairs and short insertion/deletion loops
      (IDLs), not only during DNA replication, but also in intermediates of homologous
      recombination. The efficiency of repair of different base-pairing errors in the
      DNA varies, and appears to depend on multiple factors, such as the physical
      structure of the mismatch and sequence context effects. These structural aspects
      of mismatch repair are poorly understood. In contrast, remarkable progress in
      understanding the biochemical role of error-recognition proteins has been made in
      the recent past. In eukaryotes, two heterodimers consisting of MutS-homologous
      proteins have been shown to share the function of mismatch recognition in vivo
      and in vitro. A first MutS homologue, MSH2, is present in both heterodimers, and
      the specificity for mismatch recognition is dictated by its association with
      either of two other MutS homologues: MSH6 for recognition of base-base mismatches
      and small IDLs, or MSH3 for recognition of IDLs only. Mismatch repair deficiency
      in cells can arise through mutation, transcriptional silencing or as a result of
      imbalanced expression of these genes.

PMID- 9931292
TI  - Rat-2 fibroblasts express specific adrenomedullin receptors, but not calcitonin
      gene-related-peptide receptors, which mediate increased intracellular cAMP and
      inhibit mitogen-activated protein kinase activity.
AB  - Rat-2 fibroblasts demonstrate specific binding of 125I-labelled rat
      adrenomedullin (KD=0.43 nM; Bmax=50 fmol/mg of protein) in the absence of 125I
      labelled calcitonin-gene-related peptide (CGRP) binding. Therefore Rat-2 cells
      were used to examine the pharmacology and signal transduction pathways of
      adrenomedullin receptors. We examined the effects of adrenomedullin, the CGRP
      receptor antagonist CGRP-(8-37) and the amylin antagonists AC187 and AC253 on
      receptor binding and cAMP production. AC253, AC187 and CGRP-(8-37) inhibited 125I
      adrenomedullin binding, with respective IC50 values of 25+/-8, 129+/-39 and 214+/
      56 nM. Adrenomedullin dose-dependently increased intracellular cAMP (approximate
      EC50=1.0 nM). CGRP-(8-37), AC253 and AC187 antagonized adrenomedullin-stimulated
      cAMP production at micromolar concentrations. Using kinase-substrate assays, Mono
      Q FPLC and 'phospho-specific' Western blotting, we found that adrenomedullin
      alone abolished basal mitogen-activated protein kinase (MAPK) activity and dose
      dependently inhibited platelet-derived-growth-factor-stimulated MAPK activity.
      Radioimmunoassay for adrenomedullin of media from Rat-2 cells showed a linear
      release of adrenomedullin-like immunoreactivity of 3.1 fmol/h per 2x10(6) cells.
      Gel-filtration chromatography showed that this adrenomedullin-like
      immunoreactivity co-eluted with synthetic rat adrenomedullin. Northern blotting
      with a rat adrenomedullin cDNA probe was used to confirm the presence of
      adrenomedullin mRNA. However, neither Northern blotting nor reverse transcriptase
      PCR showed the presence of the cloned adrenomedullin receptor (L1). We conclude
      that the Rat-2 cell line expresses a specific adrenomedullin receptor (coupled to
      cAMP production and regulation of MAPK) and secretes adrenomedullin, which may
      participate in a regulatory control loop.

PMID- 9931294
TI  - Synthesis and characterization of bactericidal oligopeptides designed on the
      basis of an insect anti-bacterial peptide.
AB  - Defensin from a beetle, Allomyrina dichotoma, is known to have anti-bacterial
      activity against Gram-positive bacteria. This peptide, which comprises 43 amino
      acid residues, was effective against methicillin-resistant Staphylococcus aureus.
      We identified the active site of beetle defensin by measuring anti-bacterial
      activity against S. aureus of 64 overlapping 12-mer peptides with either a free
      carboxylate or a free amide group at their C-termini. An LCAAHCLAIGRR-NH2 (19L
      30R-NH2) fragment showed the greatest activity of the synthetic oligopeptides.
      The 19L-30R-NH2 fragment was effective against both Gram-positive and Gram
      negative bacteria. CD spectra showed that the 19L-30R-NH2 fragment formed an
      alpha-helical structure in the lipidic environment. The anti-bacterial effect of
      the 19L-30R-NH2 fragment was due to its interaction with bacterial membranes,
      judging from the leakage of liposome-entrapped glucose. Its anti-bacterial
      activity was increased when certain amino acid residues were replaced. Truncated
      peptides having had some amino acids removed from the N-terminus of the 19L-30R
      NH2 fragment (8-10-mer peptides) still had strong anti-bacterial activity.
      Deleting some amino acids from the C-terminal region of the fragment dramatically
      reduced activity, indicating that the C-terminal region of the 19L-30R-NH2
      fragment, i.e. RR-NH2, is important for exerting anti-bacterial activity. The
      AHCLAIGRR-NH2 (22A-30R-NH2) fragment and its analogues exhibited about 3-fold and
      9-12-fold higher activity against S. aureus than did the 19L-30R-NH2 fragment,
      and these analogues were effective against methicillin-resistant S. aureus and
      Pseudomonas aeruginosa isolated from patients. These oligopeptides showed no
      haemolytic activity and did not inhibit the growth of murine fibroblast cells.

PMID- 9931295
TI  - Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor
      receptor but enhances its downstream signalling.
AB  - SHP-2 is a widely distributed Src homology 2 (SH2) domain-containing tyrosine
      phosphatase that is recruited to growth factor receptors on stimulation. We have
      transiently co-expressed several catalytically active and inactive forms of the
      enzyme with the platelet-derived growth factor (PDGF) receptor in human embryonic
      kidney 293 cells. The catalytically active forms of SHP-2 decreased the tyrosine
      phosphorylation of the receptor, whereas the catalytically inactive forms
      increased the phosphorylation. However, PDGF-induced activation of the mitogen
      activated protein (MAP) kinase pathway was enhanced by the active forms of SHP-2
      but decreased by the inactive forms. The results suggest that the PDGF receptor
      is a physiological substrate of SHP-2 and that SHP-2 has a positive role in the
      PDGF-stimulated activation of MAP kinase. The dissociation of the receptor
      phosphorylation from the activation of MAP kinase suggests that signalling
      through growth factor receptors does not depend merely on their tyrosine
      phosphorylation.

PMID- 9931296
TI  - Alternatively spliced mRNA variants of chloroplast ascorbate peroxidase
      isoenzymes in spinach leaves.
AB  - We have previously shown that stromal and thylakoid-bound ascorbate peroxidase
      (APX) isoenzymes of spinach chloroplasts arise from a common pre-mRNA by
      alternative splicing in the C-terminus of the isoenzymes [Ishikawa, Yoshimura,
      Tamoi, Takeda and Shigeoka (1997) Biochem. J. 328, 795-800]. To explore the
      production of mature, functional mRNA encoding chloroplast APX isoenzymes,
      reverse transcriptase-mediated PCR and S1 nuclease protection analysis were
      performed with poly(A)+ RNA or polysomal RNA from spinach leaves. As a result,
      four mRNA variants, one form of thylakoid-bound APX (tAPX-I) and three forms of
      stromal APX (sAPX-I, sAPX-II and sAPX-III), were identified. The sAPX-I and sAPX
      III mRNA species were generated through the excision of intron 11; they encoded
      the previously identified sAPX protein. Interestingly, the sAPX-II mRNA was
      generated by the insertion of intron 11 between exons 11 and 12. The use of this
      insertional sequence was in frame with the coding sequence and would lead to the
      production of a novel isoenzyme containing a C-terminus in which a seven-residue
      sequence replaced the last residue of the previously identified sAPX. The
      recombinant novel enzyme expressed in Escherichia coli showed the same enzymic
      properties (except for molecular mass) as the recombinant sAPX from the
      previously identified sAPX-I mRNA, suggesting that the protein translated from
      the sAPX-II mRNA is functional as a soluble APX in vivo. The S1 nuclease
      protection analysis showed that the expression levels of mRNA variants for sAPX
      and tAPX isoenzymes are in nearly equal quantities throughout the spinach leaves
      grown under normal conditions. The present results demonstrate that the
      expression of chloroplast APX isoenzymes is regulated by a differential splicing
      efficiency that is dependent on the 3'-terminal processing of ApxII, the gene
      encoding the chloroplast APX isoenzymes.

PMID- 9931297
TI  - Cell-cycle-regulated phosphorylation of cAMP response element-binding protein:
      identification of novel phosphorylation sites.
AB  - We report that the cAMP response element binding protein (CREB) undergoes cell
      cycle-regulated phosphorylation. In human amnion FL cells, CREB was expressed as
      two forms with different molecular masses, 45 and 45.5 kDa. Although asynchronous
      cells contained predominantly the 45 kDa forms, this form shifted to 45.5 kDa
      when the cells were synchronized with the early S-phase. Furthermore the
      expression of the 45.5 kDa band was increased when cells were treated with
      okadaic acid, confirming that the 45.5 kDa band was a phosphorylated form of the
      45 kDa band. Mutation analysis indicated that neither Ser133, the target of cAMP
      dependent protein kinase and calcium calmodulin kinase, nor Ser129, the target of
      glycogen synthetase kinase 3, was responsible for the expression of the 45.5 kDa
      band, but that Ser108, Ser111 and Ser114, located in a region matching the
      consensus sequence for the casein kinase II target, were required. A mutant in
      which Ser111 and Ser114 were each replaced by a glutamic residue, mimicking a
      phosphorylated state, had a higher activation potential in cAMP response element
      mediated transcription. These results strongly suggest that the casein kinase II
      target region is involved in cell cycle-regulated phosphorylation of the CREB
      protein and also in transcriptional enhancement.

PMID- 9931298
TI  - 6-Phosphogluconate dehydrogenase from Lactococcus lactis: a role for arginine
      residues in binding substrate and coenzyme.
AB  - A gene encoding 6-phosphogluconate dehydrogenase (6-PGDH, EC 1.1.1. 44) was
      identified from the homofermentative lactic acid bacterium Lactococcus lactis, by
      complementation of Escherichia coli mutants. The cloned gene was then expressed
      to high levels in E. coli and the protein purified for kinetic analysis. The
      enzyme had a Km for 6-phosphogluconate of 15.4+/-1.4 microM and for NADP of 1.9+/
      0.2 microM at pH 7.5. Sequence comparison of the L. lactis 6-PGDH with the
      corresponding enzyme derived from the pathogenic protozoan Trypanosoma brucei and
      sheep liver revealed the substrate-binding residues to be identical in all three
      species, although the three coenzyme-binding pockets differed slightly. A totally
      conserved arginine residue (Arg-447), believed to bind the 6-phosphate of
      substrate, was mutated to lysine, aspartate, alanine or tryptophan. In each case
      enzyme activity was lost, confirming an essential role for this residue on
      activity. A second arginine (Arg-34), believed to be critical in binding the 2'
      phosphate of cofactor NADP+, was mutated to a tyrosine residue, as found in one
      atypical isoform of the enzyme in Bacillus subtilis. This alteration led to
      decrease in affinity for NADP+ of nearly three orders of magnitude. A second 6
      PGDH gene has been identified from the genome of B. subtilis. This second isoform
      contains an arginine (Arg-34) in this position, suggesting that B. subtilis has
      two 6-PGDHs with different coenzyme specificities.

PMID- 9931299
TI  - Transmembrane 4 superfamily protein CD151 (PETA-3) associates with beta 1 and
      alpha IIb beta 3 integrins in haemopoietic cell lines and modulates cell-cell
      adhesion.
AB  - CD151 (PETA-3/SFA-1) is a member of the transmembrane 4 superfamily (TM4SF) of
      cell-surface proteins and is expressed abundantly both on the cell surface and in
      intracellular membranes by the haemopoietic cell lines M07e, HEL and K562. In the
      presence of mild detergent (CHAPS), CD151 co-immunoprecipitated with integrin
      alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha IIb beta 3. The
      association of CD151 with alpha 4 beta 1 and alpha 5 beta 1 seemed to be
      constitutive, as it was not modified by treatment of M07e cells with cytokines
      that regulate integrin function by 'inside-out' signalling. CD151 also associated
      with other tetraspans in an apparently cell-type-specific fashion, as defined by
      its co-precipitation with CD9, CD63 and CD81 from M07e cells, but not from K562
      cells, which express similar levels of these proteins. F(ab')2 fragments of
      monoclonal antibodies (mAbs) against CD151 caused homotypic adhesion of HEL and
      K562 cells that was dependent on energy and cytoskeletal integrity and was
      augmented in the presence of RGDS peptides. The adhesion was not blocked by
      function-inhibiting mAbs against beta 1 or beta 3 integrins, suggesting that cell
      cell adhesion was not mediated by the binding of integrin to a cell-associated
      ligand. Furthermore, mAb CD151 did not affect adhesion of the cells to
      fibronectin, laminin, collagen or fibrinogen, which are ligands for alpha 4 beta
      1, alpha 5 beta 1, alpha 6 beta 1 and alpha IIb beta 3 integrins. Taken together,
      these results indicate that the ligation of CD151 does not induce the up
      regulation of integrin avidity, but might act as a component of integrin
      signalling complexes.

PMID- 9931300
TI  - Incorporation of iron by the unusual dodecameric ferritin from Listeria innocua.
AB  - The polypeptide chain that assembles into the unusual dodecameric shell of
      Listeria innocua apoferritin lacks the ferroxidase centre characteristic of H
      type mammalian chains, but is able to catalyse both Fe(II) oxidation and
      nucleation of the iron core. A cluster of five carboxylate residues, which
      correspond in part to the site of iron core nucleation typical of L-type
      mammalian ferritins, has been proposed to be involved in both functions. The
      features of the iron uptake kinetics and of Fe(II) autoxidation in the presence
      of citrate followed spectrophotometrically confirm this assignment. In Listeria
      the kinetics of iron uptake is hyperbolic at low Fe(II)-to-dodecamer ratios and
      becomes sigmoidal when iron exceeds 150 Fe(II) atoms per dodecamer, namely when a
      fast crystal growth phase follows a slow initial nucleation step. Iron
      autoxidation in the presence of citrate displays a similar behaviour. Thus the
      time course is sigmoidal at low citrate-to-Fe ratios at which Fe(III)
      polymerization is predominant, but is hyperbolic at ligand concentrations high
      enough to prevent polymerization. The marked inhibitory effect of Tb(III) on the
      kinetics of iron incorporation confirms that carboxylates provide the iron
      ligands in L. innocua apoferritin. Iron uptake followed in steady-state
      fluorescence experiments allows one to distinguish Fe(II) binding and oxidation
      from the subsequent movement of Fe(III) into the apoferritin cavity as in
      mammalian ferritins despite the different localization of the tryptophan
      residues.

PMID- 9931301
TI  - Expression and purification of the first nucleotide-binding domain and linker
      region of human multidrug resistance gene product: comparison of fusions to
      glutathione S-transferase, thioredoxin and maltose-binding protein.
AB  - Many membrane proteins that belong to the ATP-binding cassette (ABC) superfamily
      are clinically important, including the cystic fibrosis transmembrane conductance
      regulator, the sulphonylurea receptor and P-glycoprotein (multidrug resistance
      gene product; MDR1). These proteins contain two multispanning transmembrane
      domains, each followed by one nucleotide-binding domain (NBD) and a linker region
      distal to the first NBD. ATP hydrolysis by the NBDs is critical for ABC protein
      function; the linker region seems to have a regulatory role. Previous attempts to
      express soluble NBDs and/or linker regions without detergent solubilization, or
      to purify NBDs at high yields as soluble fusion proteins, have been unsuccessful.
      Here we present a system for the expression in Escherichia coli of the first NBD
      of MDR1 followed by its linker region (NBD1MLD). A comparison of the expressions
      of NBD1MLD fused to glutathione S-transferase, thioredoxin and maltose-binding
      protein (MBP) shows that a high level of expression in the soluble fraction
      (approx. 8% of total E. coli protein) can be achieved only for MBP-NBD1MLD. The
      addition of a proteolytic thrombin site just proximal to the N-terminal end of
      NBD1MLD allows the cleavage of NBD1MLD from MBP, which can be easily purified
      with retention of its ATPase activity. In summary, success was obtained only when
      using an MBP fusion protein vector containing a thrombin proteolytic site between
      MBP and NBD1MLD. The approach described here could be generally applicable to
      solving the problems of expression and purification of NBDs/linker regions of ABC
      proteins.

PMID- 9931302
TI  - Brain spectrin (fodrin) interacts with phospholipids as revealed by intrinsic
      fluorescence quenching and monolayer experiments.
AB  - We demonstrate that phospholipid vesicles affect the intrinsic fluorescence of
      isolated brain spectrin. In the present studies we tested the effects of vesicles
      prepared from phosphatidylcholine (PtdCho) alone, in addition to vesicles
      containing PtdCho mixed with other phospholipids [phosphatidylethanolamine
      (PtdEtn) and phosphatidylserine] as well as from total lipid mixture extracted
      from brain membrane. The largest effect was observed with PtdEtn/PtdCho (3:2
      molar ratio) vesicles; the effect was markedly smaller when vesicles were
      prepared from egg yolk PtdCho alone. Brain spectrin injected into a subphase
      induced a substantial increase in the surface pressure of monolayers prepared
      from phospholipids. Results obtained with this technique indicated that the
      largest effect is again observed with monolayers prepared from a PtdEtn/PtdCho
      mixture. The greatest effect was observed when the monolayer contained 50-60%
      PtdEtn in a PtdEtn/PtdCho mixture. This interaction occurred at salt and pH
      optima close to physiological conditions (0.15 M NaCl, pH7.5). Experiments with
      isolated spectrin subunits indicated that the effect of the beta subunit on the
      monolayer surface pressure resembled that measured with the whole molecule.
      Similarly to erythrocyte spectrin-membrane interactions, brain spectrin
      interactions with PtdEtn/PtdCho monolayer were competitively inhibited by
      isolated erythrocyte ankyrin. This also suggests that the major phospholipid
      binding site is located in the beta subunit and indicates the possible
      physiological significance of this interaction.

PMID- 9931303
TI  - Regulation of the gene for human dipeptidyl peptidase IV by hepatocyte nuclear
      factor 1 alpha.
AB  - Hepatocyte nuclear factor 1 was identified as the transcription factor binding to
      a 20 bp (-150 to -131) region of the gene for human dipeptidyl peptidase IV,
      which has been shown to be important for the expression of dipeptidyl peptidase
      IV in the human intestinal and hepatic epithelial cell lines Caco-2 and HepG2.
      Functional analysis of the hepatocyte nuclear factor 1 site was performed with
      two minimal dipeptidyl peptidase IV promoter constructs (-250 to -41, and -150 to
      -41) with and without a 3 bp mutation in the hepatocyte nuclear factor 1
      sequence, and used in transient transfection experiments with Caco-2 cells. The
      results show that the mutated constructs were able to drive transcription at only
      5-10% of the activity of the non-mutated controls. Co-transfection of 3T3 cells
      with hepatocyte nuclear factor 1 (alpha or beta) and dipeptidyl peptidase IV
      promoter constructs (-250 to -41 or -150 to -41) resulted in a 2.5-6-fold
      increase in transcription over controls with hepatocyte nuclear factor 1 alpha
      but not with hepatocyte nuclear factor 1 beta. The results of this study show
      that hepatocyte nuclear factor 1 binds to the -150 to -131 region of the human
      dipeptidyl peptidase IV promoter and is necessary for transcriptional activation
      of the gene for dipeptidyl peptidase IV.

PMID- 9931304
TI  - The major phosphorylation site of the NADPH oxidase component p67phox is Thr233.
AB  - Phosphorylation of p67phox was shown to increase two- to three-fold upon
      stimulation by PMA, N-formylmethionyl-leucylphenylalanine or serum-opsonized
      zymosan. Phosphopeptide mapping showed one major tryptic peptide for p67phox
      immunoprecipitated from resting or stimulated cells. In vitro phosphorylation of
      p67phox by isolated cytosol or mitogen-activated protein kinase also generated
      the same phosphopeptide. Results of cyanogen bromide digestion and HPLC-MS
      suggested that Thr233 was the phosphorylated residue. Mutagenesis of Thr233 to
      alanine resulted in loss of phosphorylation in vitro. In the present work, Thr233
      has been identified as the major phosphorylation site of p67phox, which is
      situated in a proline-rich domain.

PMID- 9931305
TI  - Inhibition of proprotein convertases-1, -7 and furin by diterpines of
      Andrographis paniculata and their succinoyl esters.
AB  - Studies were performed to investigate the prohormone/proprotein convertase (PC)
      inhibitory properties of chemical constituents of the medicinally active plant
      Andrographis paniculata (AP; from the family Acanthaceae), also known as 'King of
      Bitters'. Among the individual components tested against the clinically important
      convertases, furin and PC1, neoandrographolide (a C3 O-glucoside derivative of
      the major constituent andrographolide) exhibited the highest inhibitory action
      with an IC50 of 53.5 microM against furin. The data further revealed that
      although andrographolide, the major bitter principle of AP, exhibited a
      relatively small enzyme inhibition (IC50=1.0 mM and Ki=200 microM against furin),
      upon succinoylation, its inhibitory action against the above convertases was
      enhanced significantly with a Ki in the low micromolar range (<30 microM),
      suggesting that a specific structural modification of the andrographolide
      skeleton may be exploited to develop a new class of non-peptide inhibitors of
      PCs. When tested against PC7, these succinoylated derivatives of andrographolide
      also displayed strong inhibitory action, with Ki values again in the low
      micromolar range. This potentially interesting observation may be attributed to
      the reported anti-HIV property of 14-dehydroandrographolide succinic acid
      monoester (DASM). It is suggested here that DASM, by virtue of this protease
      inhibitory property, possibly acts by suppressing the proteolytic cleavage of
      envelope glycoprotein gp160 of HIV, which is known to be PC-mediated,
      particularly by furin and PC7.

PMID- 9931306
TI  - Presence of enolase in the M-band of skeletal muscle and possible indirect
      interaction with the cytosolic muscle isoform of creatine kinase.
AB  - Glycerol-skinned skeletal muscle fibres retain the defined sarcomeric structure
      of the myofibrils. We show here that a small fraction of two enzymes important
      for energy metabolism, the cytosolic muscle isoform of creatine kinase (EC
      2.7.3.2), MM-creatine kinase (MM-CK), and enolase (EC 4.2.1.11), remains bound to
      skinned fibres. CK is slowly exchangeable, whereas enolase is firmly bound. Two
      dimensional gel electrophoresis followed by Western blot analyses demonstrates
      that both alpha (ubiquitous) and beta (muscle-specific) subunits of enolase are
      present in these preparations. Enolase and CK were co-localized at the M-band of
      the sarcomeres, as observed by indirect immunofluorescence and confocal
      microscopy. Cross-linking experiments were performed on skinned fibres with three
      bifunctional succinimidyl esters of different lengths and yielded a protein
      complex of 150 kDa that reacted with antibodies directed against either M-CK or
      beta-enolase. The cross-linking efficiency was greatest for the longest reagent
      and zero for the shortest one. The length of the cross-linker giving a covalent
      complex between the two enzymes does not support the notion of a direct
      interaction between M-CK and enolase. This is the first demonstration of the
      presence of an enzyme of energy metabolism other than CK at the M-band of
      myofibres.

PMID- 9931307
TI  - Purification of intracellular compartments involved in antigen processing: a new
      method based on magnetic sorting.
AB  - In the present study, we describe a method to specifically isolate intracellular
      compartments containing endocytosed antigen. We have demonstrated that isolated
      compartments represent a small proportion of the intracellular material, highly
      enriched in antigen. Antigen-containing vesicles are specifically sorted from
      other intracellular compartments, such as endoplasmic reticulum or Golgi
      apparatus, and from the plasma membrane. They remain functional in vitro since
      they can be acidified, and the antigen inside has been found to be partially
      proteolysed. In macrophages, kinetic analysis has revealed that the antigen is
      first found in compartments of endosomal density, carrying Rab 5 and Rab 7, then
      in late compartments of lysosomal density, which are rich in proteases. The
      global protein content of the compartments was mapped by two-dimensional
      electrophoresis. In B lymphocytes, this method has allowed the isolation of
      endocytic compartments emerging from receptor-mediated endocytosis of the
      antigen. After 2 h of chase, the antigen reached vesicles containing large
      amounts of MHC-class II molecules, invariant chain and human leucocyte antigen
      DM, where peptide loading can occur.

PMID- 9931308
TI  - A transforming mutation enhances the activity of the c-Kit soluble tyrosine
      kinase domain.
AB  - An activating mutation (DY814) located in the catalytic domain of the c-Kit
      receptor has been found in mastocytomas from human, mouse and rat. We evaluated
      the enzymic properties of purified wild-type (WT) and DY814 tyrosine kinase
      domains expressed in Pichia pastoris. A linker encoding the Flag epitope was
      fused to c-Kit cDNA species, enabling affinity purification of the proteins with
      anti-Flag antibodies. Yeast lysates expressing DY814 contained multiple tyrosine
      phosphorylated proteins, whereas WT lysates had no detectable tyrosine
      phosphorylation. Purification of the WT and mutant kinases in the presence of
      vanadate demonstrated that both enzymes undergo autophosphorylation. Kinetic
      analyses of WT and DY814 kinases indicated that at 20 nM enzyme concentration the
      mutation increases the specific activity 10-fold and decreases the apparent Km
      for ATP 9-fold. WT activity displayed a hyperbolic dependence on enzyme
      concentration, consistent with a requirement for dimerization or aggregation for
      activity. This activity was also enhanced by anti-Flag antibodies. In contrast,
      the dependence of DY814 activity on enzyme concentration was primarily linear and
      only marginally enhanced by anti-Flag antibodies. Gel-filtration analysis showed
      that the WT kinase migrated as a monomer, whereas the DY814 mutant migrated as a
      dimer. These results indicate that this point mutation promotes dimerization of
      the c-Kit kinase, potentially contributing to its transforming potential in mast
      cells.

PMID- 9931309
TI  - Characterization of the 70 kDa polypeptide of the Na/Ca exchanger.
AB  - The Na/Ca exchanger is associated with 160, 120 and 70 kDa polypeptides whose
      nature is poorly understood. We have purified and characterized the Na/Ca
      exchanger from bovine cardiac sarcolemmal vesicles (SLVs) by using ion-exchange
      and affinity chromatographies. The Na/Ca exchanger-enriched fraction was
      reconstituted into asolectin liposomes [lipid to protein ratio 10:1 (w/w)] that
      showed Na/Ca exchange activity. Under non-reducing conditions, SDS/PAGE showed a
      single 70 kDa polypeptide, which was further characterized by immunoblots with
      different antibodies: SWant, raised against the purified exchanger protein; NH2
      terminus, residues 1-21; NCX1, residues 393-406; and Exon F, residues 622-644.
      Immunoblots under reducing conditions with SWant, NH2-terminus and NCX1 showed
      three bands migrating at 160, 120 and 70 kDa for SLV preparations, whereas Exon F
      reacted only with the 160 and 120 kDa bands. Under non-reducing conditions,
      immunoblots with purified reconstituted Na/Ca exchanger showed a single band at
      70 kDa reacting with SWant, NH2-terminus and NCX1 but not with Exon F. We
      conclude that the 70 kDa protein is associated with Na/Ca exchange activity, has
      the same N-terminal sequence as the cloned bovine cardiac exchanger, and has its
      length decreased by at least 35% from its C-terminal portion as compared with
      that of the wild-type exchanger.

PMID- 9931310
TI  - Predominance of the acylation route in the metabolic processing of exogenous
      sphingosine in neural and extraneural cells in culture.
AB  - The metabolic fate of exogenous [3H]sphingosine was investigated in five types of
      cultured cells: primary cultures of neurons and astrocytes, murine and human
      neuroblastoma cells and human skin fibroblasts. After administration of 40 nM [3
      3H]sphingosine into a cell-conditioned medium containing fetal calf serum, all
      cell types rapidly and efficiently incorporated the long-chain base in a time
      dependent fashion. In all cases, after a 120 min pulse, the amount of
      radioactivity taken up was in the range of the endogenous sphingosine content.
      However, unchanged [3H]sphingosine represented only a very minor portion of the
      label incorporated into cells throughout the pulse period (10-120 min),
      indicating rapid and efficient sphingosine metabolism in these cells. Most of the
      [3H]sphingosine taken up was metabolically processed, either by degradation
      (assessed as 3H2O release into the culture medium) or by N-acylation (mainly to
      radioactive ceramide, sphingomyelin, neutral glycolipids and gangliosides).
      [3H]Sphingosine 1-phosphate accounted for less than 2% of the total radioactivity
      incorporated in all cases. Throughout the pulse period and in all cell types, 3H
      labelled organic metabolites largely prevailed over 3H2O, indicating that N
      acylation is the major metabolic fate of sphingosine in these cells under
      apparently physiological conditions. These results are consistent with the notion
      that sphingosine has a rapid turnover in the cells studied, and indicate that
      regulation of the basal level of this bioactive molecule occurs mainly through N
      acylation.

PMID- 9931311
TI  - Hydrogen bonding and protein perturbation in beta-lactam acyl-enzymes of
      Streptococcus pneumoniae penicillin-binding protein PBP2x.
AB  - A soluble form of Streptococcus pneumoniae PBP2x, a molecular target of
      penicillin and cephalosporin antibiotics, has been expressed and purified. IR
      difference spectra of PBP2x acylated with benzylpenicillin, cloxacillin,
      cephalothin and ceftriaxone have been measured. The difference spectra show two
      main features. The ester carbonyl vibration of the acyl-enzyme is ascribed to a
      small band between 1710 and 1720 cm-1, whereas a much larger band at approx. 1640
      cm-1 is ascribed to a perturbation in the structure of the enzyme, which occurs
      on acylation. The protein perturbation has been interpreted as occurring in beta
      sheet. The acyl-enzyme formed with benzylpenicillin shows the lowest ester
      carbonyl vibration frequency, which is interpreted to mean that the carbonyl
      oxygen is the most strongly hydrogen-bonded in the oxyanion hole of the
      antibiotics studied. The semi-synthetic penicillin cloxacillin is apparently less
      well organized in the active site and shows two partially overlapping ester
      carbonyl bands. The penicillin acyl-enzyme has been shown to deacylate more
      slowly than that formed with cloxacillin. This demonstrates that the natural
      benzylpenicillin forms a more optimized and better-bonded acyl-enzyme and that
      this in turn leads to the stabilization of the acyl-enzyme required for effective
      action in the inhibition of PBP2x. The energetics of hydrogen bonding in the
      several acyl-enzymes is discussed and comparison is made with carbonyl absorption
      frequencies of model ethyl esters in a range of organic solvents. A comparison of
      hydrolytic deacylation with hydroxaminolysis for both chymotryspin and PBP2x
      leads to the conclusion that deacylation is uncatalysed.

PMID- 9931312
TI  - Activation of caspase-3-like proteases in apoptosis induced by sphingosine and
      other long-chain bases in Hep3B hepatoma cells.
AB  - Sphingosine and other long-chain bases (including sphinganine,
      dimethylsphingosine and stearylamine), but not octylamine (a short-chain analogue
      of sphinganine), induced apoptosis in Hep3B hepatoma cells. Because both D- and L
      erythrosphingosine and stearylamine exert potent apoptotic effects on Hep3B
      cells, it is possible that these long-chain bases may activate apoptosis by
      inhibiting protein kinase C (PKC) activity. However, pretreatment with the PKC
      activator PMA could not rescue cells from apoptosis triggered by long-chain
      bases. Therefore the involvement of PKC in this apoptotic process requires
      further characterization. We also investigated whether these long-chain bases
      might be metabolized into ceramide in order to elicit their apoptotic action. We
      found that long-chain bases acted independently of ceramide in the induction of
      apoptosis, since addition of fumonisin B1, a fungal agent which effectively
      inhibits ceramide synthesis from sphingosine, did not protect against apoptosis.
      Additionally, we found that sphingosine-induced apoptosis was accompanied by
      activation of caspases. The functional role of caspases in this apoptotic process
      was examined by using specific caspase inhibitors. The general caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone, which exhibits a broad
      specificity for caspase-family proteases, effectively blocked sphingosine-induced
      apoptosis. Furthermore, our results indicate that caspase-3-like proteases, but
      not caspase-1, are activated during apoptosis triggered by sphingosine.
      Enhancement of caspase-3-like activity and cleavage of poly(ADP-ribose)
      polymerase, an in vivo substrate for caspase-3, was clearly demonstrated in
      sphingosine-treated Hep3B cells. Considered together, these results suggest that
      caspase-3-like proteases participate in apoptotic cell death induced by
      sphingosine.

PMID- 9931313
TI  - Control of sarcoplasmic/endoplasmic-reticulum Ca2+ pump expression in cardiac and
      smooth muscle.
AB  - Cardiac muscle expresses sarcoplasmic/endoplasmic-reticulum Ca2+ pump isoform
      SERCA2a; stomach smooth muscle expresses SERCA2b. In 2-day-old rabbits, cardiac
      muscle contained levels of SERCA2 protein that were 100-200-fold those in the
      stomach smooth muscle. In nuclear run-on assays, the rate of SERCA2 gene
      transcription in heart nuclei was not significantly higher than in the stomach
      smooth-muscle nuclei. However, the SERCA2 mRNA levels (mean+/-S.E.M.) were (29+/
      4)-fold higher in the heart. In both tissues the SERCA2 mRNA was associated with
      polyribosomes. In a sucrose-density-gradient sedimentation velocity experiment on
      polyribosomes, there was no difference in the sedimentation pattern of SERCA2
      mRNA between the two tissues, suggesting that the translation efficiency of
      SERCA2 RNA in the two tissues is quite similar. Thus the main difference in the
      control of SERCA2 expression in the two tissues is post-transcriptional and
      pretranslational.

PMID- 9931314
TI  - Agonist-induced desensitization and phosphorylation of m1-muscarinic receptors.
AB  - Pre-stimulation of Chinese hamster ovary (CHO) cells expressing the human m1
      muscarinic receptor (CHO-m1 cells) with a maximally effective concentration of
      the muscarinic agonist methacholine resulted in desensitization of Ins(1,4,5)P3
      accumulation, apparent as a approximately 4-fold shift in the agonist dose
      response curve. Agonist-induced desensitization was rapid (detectable by 10 s)
      and concentration dependent (EC50=8.2+/-2.2 microM) and resulted in a complete
      loss of receptor reserve for the agonist-stimulated Ins(1,4, 5)P3 response. An
      investigation of the possible mechanisms involved in m1-muscarinic receptor
      desensitization indicated that agonist-induced receptor internalization, PtdIns
      (4,5)P2 depletion or an increased rate of Ins(1,4,5)P3 metabolism were not
      involved. m1-Muscarinic receptors did, however, undergo rapid agonist-induced
      phosphorylation with a time course that was consistent with an involvement in
      receptor desensitization. Characterization studies indicated that the receptor
      specific kinase involved was distinct from protein kinase C and other second
      messenger-dependent protein kinases. Since previous studies have suggested that
      the m3-muscarinic receptor subtype undergoes agonist-dependent phosphorylation
      via casein kinase 1alpha (CK1alpha) [Tobin, Totty, Sterlin and Nahorski (1997) J.
      Biol. Chem. 272, 20844-20849], we examined the ability of m1-muscarinic receptors
      to be phosphorylated by this kinase. In reconstitution experiments, CK1alpha was
      able to phosphorylate purified, soluble m1-muscarinic receptors in an agonist
      dependent manner.

PMID- 9931316
TI  - The folding and assembly of the dodecameric type II dehydroquinases.
AB  - The dodecameric type II dehydroquinases (DHQases) have an unusual quaternary
      structure in which four trimeric units are arranged with cubic 23 symmetry. The
      unfolding and refolding behaviour of the enzymes from Streptomyces coelicolor and
      Mycobacterium tuberculosis have been studied. Gel-permeation studies show that,
      at low concentrations (0.5 M) of guanidinium chloride (GdmCl), both enzymes
      dissociate into trimeric units, with little or no change in the secondary or
      tertiary structure and with a 15% loss (S. coelicolor) or a 55% increase (M.
      tuberculosis) in activity. At higher concentrations of GdmCl, both enzymes
      undergo sharp unfolding transitions over narrow ranges of the denaturant
      concentration, consistent with co-operative unfolding of the subunits. When the
      concentration of GdmCl is lowered by dilution from 6 M to 0.55 M, the enzyme from
      S. coelicolor refolds in an efficient manner to form trimeric units, with more
      than 75% regain of activity. Using a similar approach the M. tuberculosis enzyme
      regains less than 35% activity. From the time courses of the changes in CD,
      fluorescence and activity of the S. coelicolor enzyme, an outline model for the
      refolding of the enzyme has been proposed. The model involves a rapid refolding
      event in which approximately half the secondary structure is regained. A slower
      folding process follows within the monomer, resulting in acquisition of the full
      secondary structure. The major changes in fluorescence occur in a second-order
      process which involves the association of two folded monomers. Regain of activity
      is dependent on a further associative event, showing that the minimum active unit
      must be at least trimeric. Reassembly of the dodecameric S. coelicolor enzyme and
      essentially complete regain of activity can be accomplished if the denatured
      enzyme is dialysed extensively to remove GdmCl. These results are discussed in
      terms of the recently solved X-ray structures of type II DHQases from these
      sources.

PMID- 9931315
TI  - Biochemical characterization of Bacillus thuringiensis cytolytic toxins in
      association with a phospholipid bilayer.
AB  - The interaction of two Bacillus thuringiensis cytolytic toxins, CytA and CytB,
      with a phospholipid bilayer and their structure in the membrane-bound state were
      investigated by proteolysis using phospholipid vesicles as a model system. A
      toxin conformational change upon membrane binding was detected by comparing the
      proteolytic profile of membrane-bound toxin and saline-solubilized toxin. When
      membrane-bound toxin was exposed to protease K or trypsin, novel cleavage sites
      were found between the alpha-helical N-terminal half and beta-strand C-terminal
      half of the structure at K154 and N155 in CytA and at I150 and G141 in CytB. N
      terminal sequencing of membrane-protected fragments showed that the C-terminal
      half of the toxin structure comprising mainly beta-strands was inserted into the
      membrane, whereas the N-terminal half comprising mainly alpha-helices was exposed
      on the outside of the liposomes and could be removed when liposomes with bound
      toxin were washed extensively after proteolysis. The C-termini of the membrane
      inserted proteolytic fragments were also located by a combination of N-terminal
      sequencing and measurement of the molecular masses of the fragments by
      electrospray MS. Using a liposome glucose-release assay, the membrane-inserted
      structure was seen to retain its function as a membrane pore even after removal
      of exposed N-terminal segments by proteolysis. These data strongly suggest that
      the pores for glucose release are assembled from the three major beta-strands
      (beta-5, beta-6 and beta-7) in the C-terminal half of the toxin.

PMID- 9931317
TI  - Evidence for the involvement of p59fyn and p53/56lyn in collagen receptor
      signalling in human platelets.
AB  - The binding of collagen to platelet glycoprotein VI (GPVI) leads to the
      subsequent activation of phospholipase Cgamma2 through a pathway that is
      dependent on the Fc receptor gamma (FcR gamma) chain and the tyrosine kinase
      p72syk. We have investigated the role of platelet Src-family kinases in this
      signalling pathway. The selective Src-family kinase inhibitor PP1 prevented
      collagen-stimulated increases in whole-cell tyrosine phosphorylation and tyrosine
      phosphorylation of the FcR gamma chain and p72syk. A similar set of observations
      was made for a collagen-related peptide (CRP), which binds to GPVI but not to the
      integrin alpha2beta1 (GPIa/IIa). These effects were seen at a concentration of
      PP1 that inhibited platelet aggregation, dense granule release and Ca2+
      mobilization induced by CRP, but not aggregation and Ca2+ mobilization mediated
      by the G-protein-coupled receptor agonist thrombin. After stimulation by CRP or
      collagen, the Src-family kinases p59fyn and p53/56lyn became associated with
      several tyrosine-phosphorylated proteins including the FcR gamma chain. This was
      not true of the other platelet Src-family kinases. The association between the
      FcR gamma chain and p59fyn was also seen under basal conditions, and was stable
      only in the weak detergent Brij96 but not in Nonidet P40, suggesting a non-SH2
      dependent interaction. These results provide strong evidence for the involvement
      of p59fyn and p53/56lyn in signalling via GPVI, with p59fyn possibly acting
      upstream of FcR gamma chain phosphorylation.

PMID- 9931318
TI  - Purification, characterization and molecular cloning of trichoanguin, a novel
      type I ribosome-inactivating protein from the seeds of Trichosanthes anguina.
AB  - The seeds of the plant Trichosanthes anguina contain a type I ribosome
      inactivating protein (RIP), designated trichoanguin, which was purified to
      apparent homogeneity by the combined use of ion-exchange chromatographies, i.e.
      first with DE-52 cellulose and then with CM-52 cellulose. The protein was found
      to be a glycoprotein with a molecular mass of 35 kDa and a pI of 9.1. It strongly
      inhibits the protein synthesis of rabbit reticulocyte lysate, with an IC50 of
      0.08 nM, but only weakly that of HeLa cells, with an IC50 of 6 microM.
      Trichoanguin cleaves at the A4324 site of rat 28 S rRNA by its N-glycosidase
      activity. The cDNA of trichoanguin consists of 1039 nt and encodes an open
      reading frame coding for a polypeptide of 294 amino acid residues. The first 19
      residues of this polypeptide encode a signal peptide sequence and the last 30
      residues comprise an extension at its C-terminus. There are four potential
      glycosylation sites, located at Asn-51, Asn-65, Asn-201 and Asn-226. A comparison
      of the amino acid sequence of trichoanguin with those of RIPs such as
      trichosanthin, alpha-momorcharin, ricin A-chain and abrin A-chain reveals 55%,
      48%, 36% and 34% identity respectively. Molecular homology modelling of
      trichoanguin indicates that its tertiary structure closely resembles those of
      trichosanthin and alpha-momorcharin. The large structural similarities might
      account for their common biological effects such as an abortifacient, an anti
      tumour agent and anti-HIV-1 activities. Trichoanguin contains two cysteine
      residues, Cys-32 and Cys-155, with the former being likely to be located on the
      protein surface, which is directly amenable for conjugation with antibodies to
      form immunoconjugates. It is therefore conceivable that trichoanguin might be a
      better type I RIP than any other so far examined for the preparation of
      immunotoxins, with a great potential for application as an effective
      chemotherapeutic agent for the treatment of cancer.

PMID- 9931319
TI  - Photodynamic action of porphyrin on Ca2+ influx in endoplasmic reticulum: a
      comparison with mitochondria.
AB  - We have studied the distribution properties of haematoporphyrin (HP) and
      protoporphyrin (PP) in mitochondria and endoplasmic reticulum after isolation
      from rat liver. The photosensitizing efficiency of porphyrin on the Ca2+ influx
      function of microsomes has been compared with that obtained on Ca2+ uptake in
      mitochondria. HP and PP are accumulated in microsomes to a greater extent than in
      mitochondria, both porphyrins binding to membrane protein sites. The Ca2+ influx
      functions of mitochondria and microsomes, before and after irradiation in the
      presence of HP or PP, were studied by following the changes in the free Ca2+
      concentration in the medium as revealed by the variations in fluorescence
      intensity of the Ca2+ indicator Calcium Green-1. For the same amount of
      incorporated porphyrin, the Ca2+ influx function of microsomes is degraded by
      irradiation more rapidly than that of mitochondria. The protective effect of
      dithiothreitol suggests that thiol groups in the Ca2+-transporting enzyme are the
      preferential targets of the photodynamic effect. These results suggest that
      intracellular Ca2+ movements are altered primarily by the endoplasmic reticulum
      rather than by mitochondrial damage, in good agreement with other observations
      made in porphyrin-loaded irradiated cells.

PMID- 9931321
TI  - The kinetics of acylation and deacylation of penicillin acylase from Escherichia
      coli ATCC 11105: evidence for lowered pKa values of groups near the catalytic
      centre.
AB  - Penicillin G acylase catalysed the hydrolysis of 4-nitrophenyl acetate with a
      kcat of 0.8 s-1 and a Km of 10 microM at pH 7.5 and 20 degreesC. Results from
      stopped-flow experiments fitted a dissociation constant of 0.16 mM for the
      Michaelis complex, formation of an acetyl enzyme with a rate constant of 32 s-1
      and a subsequent deacylation step with a rate constant of 0.81 s-1. Non-linear
      Van't Hoff and Arrhenius plots for these parameters, measured at pH 7.5, may be
      partly explained by a conformational transition affecting catalytic groups, but a
      linear Arrhenius plot for the ratio of the rate constant for acylation relative
      to KS was consistent with energy-compensation between the binding of the
      substrate and catalysis of the formation of the transition state. At 20 degreesC,
      the pH-dependence of kcat was similar to that of kcat/Km, indicating that
      formation of the acyl-enzyme did not affect the pKa values (6.5 and 9.0) of an
      acidic and basic group in the active enzyme. The heats of ionization deduced from
      values of pKa for kcat, which measures the rate of deacylation, are consistent
      with alpha-amino and guanidinium groups whose pKa values are decreased in a non
      polar environment. It is proposed that, for catalytic activity, the alpha-amino
      group of the catalytic SerB1 and the guanidinium group of ArgB263 are required in
      neutral and protonated states respectively.

PMID- 9931320
TI  - Spontaneous activation of NADPH oxidase in a cell-free system: unexpected
      multiple effects of magnesium ion concentrations.
AB  - The role of magnesium ions in the activation of NADPH oxidase has been
      investigated using flavocytochrome b-245 and either neutrophil cytosol or
      mixtures of recombinant p40phox, p47phox, p67phox and Rac2. Purified
      flavocytochrome b-245 is highly active (turnover number 120-150 mol of O2(-)/s
      per mol of cytochrome haem) in the absence of Mg2+, in marked contrast to
      neutrophil membranes or detergent-solubilized membranes, which have an absolute
      requirement for Mg2+ for NADPH oxidase activity. It was also found that Mg2+
      affected the anionic amphiphile requirement for oxidase activation, and this was
      dependent on whether neutrophil cytosol or mixtures of recombinant cytosolic
      proteins were used in the assay. Unexpectedly we found that, using purified
      flavocytochrome b-245 and recombinant cytosolic proteins, NADPH oxidase undergoes
      spontaneous activation in the absence of anionic amphiphiles under Mg2+-free
      conditions. The results suggest that Mg2+ ions play an important role in NADPH
      oxidase function, perhaps stabilizing the 260 kDa complex of cytosolic phox
      proteins or the regulation of a guanine nucleotide-binding protein. We provide
      evidence that if the latter explanation is correct, the identity of the guanine
      nucleotide-binding protein is unlikely to be Rap1a.

PMID- 9931322
TI  - Repetitive conundrums of centromere structure and function.
AB  - In the last few years, a paradox has emerged regarding the relationship of
      centromere structure and its function. Most centromeric DNAs analyzed to date are
      composed of a remarkably complex array of repeat structures. In contrast, recent
      analyses of neocentromeric DNA reveal that repetitive DNA is not a prerequisite
      for centromere activity. The ubiquity of repetitive sequences among diverse
      species at sites of primary constriction argues that there is a strong
      evolutionary link between centromere structure and function. Dynamic mutational
      processes resulting in amplification, deletion and transposition of repetitive
      sequences appear to occur frequently in such regions, resulting in considerable
      interspecific diversity in structure and sequence. One possible solution to this
      conundrum may be that the rapid accumulation of repetitive sequences within
      centromeric and pericentromeric DNA is a consequence of functionally active
      centromeres. Emerging repetitive structures at centromeric sites may be an
      important byproduct of a functional centromere which ensures that site as an
      evolutionarily favored position in subsequent meiotic and mitotic lineages. The
      recent identification of large gene duplications in the vicinity of centromeres
      may be another example of the enhanced mutational lability of such regions of the
      genome.

PMID- 9931323
TI  - Deletions of the heavy neurofilament subunit tail in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degeneration
      resulting in paralysis and death, usually within 3 years of onset. Pathological
      and animal studies implicate neurofilament involvement in ALS, but whether this
      is primary or secondary is not clear. The heavy neurofilament subunit (NFH) tail
      is composed of a repeating amino acid motif, usually X-lysine-serine-proline-Y
      lysine (XKSPYK), where X is a single amino acid and Y is one to three amino
      acids. There are two common polymorphic variants of 44 or 45 repeats. The tail
      probably regulates axonal calibre, with interfilament spacing determined by
      phosphorylation of the KSP motifs. A previous study suggested an association
      between sporadic cases of ALS and NFH tail deletions, but two subsequent studies
      have found none. We have analysed samples from two different populations (UK 207,
      Scandinavia 323) with age-matched controls for each group (UK 219, Scandinavia
      228) and have found four novel NFH tail deletions, each involving a whole motif.
      These were found in three patients with sporadic ALS and a family with autosomal
      dominant ALS, although another was also found in two young controls. In all cases
      motif deletions were only associated with disease when paired with the long NFH
      allele. The deletions all occurred within a small region of the NFH tail. This
      has allowed us to propose a structural organization of the tail as well as
      allowing observed deletions both from this study and previous reports to be
      organized into logical groups. These results strongly suggest that NFH motif
      deletions can be a primary event in ALS but that they are not common.

PMID- 9931324
TI  - Missense mutations in the most ancient residues of the PAX6 paired domain
      underlie a spectrum of human congenital eye malformations.
AB  - Mutations of the human PAX6 gene underlie aniridia (congenital absence of the
      iris), a rare dominant malformation of the eye. The spectrum of PAX6 mutations in
      aniridia patients is highly biased, with 92% of all reported mutations leading to
      premature truncation of the protein (nonsense, splicing, insertions and
      deletions) and just 2% leading to substitution of one amino acid by another
      (missense). The extraordinary conservation of the PAX6 protein at the amino acid
      level amongst vertebrates predicts that pathological missense mutations should in
      fact be common even though they are hardly ever seen in aniridia patients. This
      indicates that there is a heavy ascertainment bias in the selection of patients
      for PAX6 mutation analysis and that the 'missing' PAX6 missense mutations
      frequently may underlie phenotypes distinct from textbook aniridia. Here we
      present four novel PAX6 missense mutations, two in association with atypical
      phenotypes: ectopia pupillae (displaced pupils) and congenital nystagmus
      (searching gaze), and two in association with more recognizable aniridia
      phenotypes. Strikingly, all four mutations are located within the PAX6 paired
      domain and affect amino acids which are highly conserved in all known paired
      domain proteins. Our results support the hypothesis that the under-representation
      of missense mutations is caused by ascertainment bias and suggest that a
      substantial burden of PAX6 -related disease remains to be uncovered.

PMID- 9931325
TI  - Analysis of germline mutation spectra at the Huntington's disease locus supports
      a mitotic mutation mechanism.
AB  - Trinucleotide repeat disease alleles can undergo 'dynamic' mutations in which
      repeat number may change when a gene is transmitted from parent to offspring. By
      typing >3500 sperm, we determined the size distribution of Huntington's disease
      (HD) germline mutations produced by 26 individuals from the Venezuelan cohort
      with CAG/CTG repeat numbers ranging from 37 to 62. Both the mutation frequency
      and mean change in allele size increased with increasing somatic repeat number.
      The mutation frequencies averaged 82% and, for individuals with at least 50
      repeats, 98%. The extraordinarily high mutation frequency levels are most
      consistent with a mutation process that occurs throughout germline mitotic
      divisions, rather than resulting from a single meiotic event. In several cases,
      the mean change in repeat number differed significantly among individuals with
      similar somatic allele sizes. This individual variation could not be attributed
      to age in a simple way or to ' cis ' sequences, suggesting the influence of
      genetic background or other factors. A familial effect is suggested in one family
      where both the father and son gave highly unusual spectra compared with other
      individuals matched for age and repeat number. A statistical model based on
      incomplete processing of Okazaki fragments during DNA replication was found to
      provide an excellent fit to the data but variation in parameter values among
      individuals suggests that the molecular mechanism might be more complex.

PMID- 9931326
TI  - PTEN is inversely correlated with the cell survival factor Akt/PKB and is
      inactivated via multiple mechanismsin haematological malignancies.
AB  - PTEN is a novel tumour suppressor gene that encodes a dual-specificity
      phosphatase with homology to adhesion molecules tensin and auxillin. It recently
      has been suggested that PTEN dephosphorylates phosphatidylinositol 3,4,5
      trisphosphate [PtdIns(3, 4,5)P3], which mediates growth factor-induced activation
      of intracellular signalling, in particular through the serine-threonine kinase
      Akt, a known cell survival-promoting factor. PTEN has been mapped to 10q23.3, a
      region disrupted in several human tumours including haematological malignancies.
      We have analysed PTEN in a series of primary acute leukaemias and non-Hodgkin's
      lymphomas (NHLs) as well as in cell lines. We have also examined whether a
      correlation could be found between PTEN and Akt levels in these samples. We show
      here that the majority of cell lines studied carries PTEN abnormalities. At the
      structural level, we found mutations and hemizygous deletions in 40% of these
      cell lines, while a smaller number of primary haematological malignancies, in
      particular NHLs, carries PTEN mutations. Moreover, one-third of the cell lines
      had low PTEN transcript levels, and 60% of these samples had low or absent PTEN
      protein, which could not be attributed to gene silencing by hypermethylation. In
      addition, we found that PTEN and phosphorylated Akt levels are inversely
      correlated in the large majority of the examined samples. These findings suggest
      that PTEN plays a role in the pathogenesis of haematological malignancies and
      that it might be inactivated through a wider range of mechanisms than initially
      considered. The finding that PTEN levels inversely correlate with phosphorylated
      Akt supports the hypothesis that PTEN regulates PtdIns(3,4,5)P3and suggests a
      role for PTEN in apoptosis.

PMID- 9931327
TI  - Xist RNA exhibits a banded localization on the inactive X chromosome and is
      excluded from autosomal material in cis.
AB  - The propagation of X chromosome inactivation is thought to be mediated by the cis
      limited spreading of the non-protein coding Xist transcript. In this report we
      have investigated the localization of Xist RNA on rodent metaphase chromosomes.
      We show that Xist RNA exhibits a banded pattern on the inactive X and is excluded
      from regions of constitutive heterochromatin. The banding pattern suggests a
      preferential association with gene-rich, G-light regions. Analysis of X:autosome
      rearrangements revealed that restricted propagation of X inactivation into cis 
      linked autosomal material is reflected by a corresponding limited spread of Xist
      RNA. We discuss these results in the context of models for the function of Xist
      RNA in the propagation of X inactivation.

PMID- 9931328
TI  - Sequences flanking the centromere of human chromosome 10 are a complex patchwork
      of arm-specific sequences, stable duplications and unstable sequences with
      homologies to telomeric and other centromeric locations.
AB  - Little is known about sequence organization close to human centromeres, despite
      empirical and theoretical data which suggest that it may be unusual. Here we
      present maps which physically define large sequence duplications flanking the
      centromeric satellites of human chromosome 10, together with a fluorescence in
      situ hybridization (FISH) analysis of pericentromeric sequence stability. Our
      results indicate that the duplications on each chromosome arm are organized into
      two blocks of approximately 250 and 150 kb separated by approximately 300 kb of
      non-duplicated DNA. The larger proximal blocks, containing ZNF11A, ZNF33A and
      ZNF37A (10p11) and ZNF11B, ZNF33B and ZNF37B (10q11), are inverted. However, the
      smaller distal blocks, containing D10S141A (10p11) and D10S141B (10q11), are not.
      A primate FISH analysis indicates that these loci were duplicated before the
      divergence of orang-utans from other Great Apes, that a cytogenetically cryptic
      pericentric inversion may have been involved in the formation of the flanking
      duplications and that they have undergone further rearrangement in other primate
      species. More surprising is the fact that sequences across the entire
      pericentromeric region appear to have undergone unprecedented levels of
      duplication, transposition, inversion and either deletion or sequence divergence
      in all primate species analysed. Extrapolating our data to the whole genome
      suggests that a minimum of 50 Mb of DNA in centromere-proximal regions is subject
      to an elevated level of mechanistically diverse sequence rearrangements compared
      with the bulk of genomic DNA.

PMID- 9931329
TI  - Sequence analysis of an 80 kb human neocentromere.
AB  - We previously described the cloning of an 80 kb DNA corresponding to the core
      protein-binding domain of a human chromosome 10-derived neocentromere. Here we
      report the complete sequence of this DNA (designated NC DNA) and its detailed
      structural analysis. The sequence is devoid of human centromeric alpha-satellite
      DNA and the pericentric beta- and gamma-satellites, the ATRS and 48 bp repeat
      DNA. One copy of a sequence that is related to the CENPB box motif is present,
      and a number of copies of other pericentric sequences including pJalpha and
      classical satellites I and III are present but both their relative sparsity and
      non-tandem organization suggest that each sequence, on its own, is unlikely to
      mimic any role the sequence may have in the normal centromere. The DNA-binding
      motifs of the architectural and regulatory proteins HMGI and topoII have a normal
      abundance and random distribution, implying that these sequences are not key
      functional elements. The total A + T content of the sequence is not notably
      different from that of the human genome, but an abundance of AT-rich islands and
      a biased distribution of these islands within the NC sequence are
      clearlydiscernible and may be functionally significant. Substantial amounts of
      transposable elements and low copy number tandem repeats, including several that
      are highly AT- and purine-rich, are also present and may act as functional
      elements. One of the AT-rich tandemrepeats (AT28) may form interesting structures
      and is described in detail. The defined features show only a loose resemblance to
      the structures of known centromeres, highlighting the possibility that, rather
      than a conserved primary sequence, it is the overallcomposition and distribution
      patterns of various unknown functional elements, or any 'ordinary' DNA under
      appropriate epigenetic influences, that determine centromere formation and
      function. This is the firstdetailed analysis of a neocentromere DNA and provides
      a basis for comparison against future sequences.

PMID- 9931330
TI  - Expression of the von Hippel-Lindau-binding protein-1 (Vbp1) in fetal and adult
      mouse tissues.
AB  - The von Hippel-Lindau (VHL) tumour suppressorgene product is believed to be
      involved in the down-regulation of transcriptional elongation by preventing the
      association of elongin B and C with the catalytic subunit elongin A. Alterations
      in the human VHL gene lead to VHL disease which is associated with various rare
      neoplasias, including haemangioblastoma of the central nervous system, retinal
      angioma, clear cell renal carcinoma and pheochromocytoma. Recently, a protein
      (VBP1) was isolated that was found to bind to the VHL protein in vivo. We have
      used the murine Vbp1 homologous cDNA to investigate the expression of the Vbp1
      mRNA in the mouse by in situ hybridization and northern blot analysis. In fetal
      stages between days 9 and 18 of gestation, Vbp1 was expressed mainly in the
      central nervous system, retina and liver. In addition, at day 12, high expression
      was observed in the labyrinthine region of the placenta. In later stage
      placentas, Vbp1 expression was, however, considerably reduced. Northern blot
      analysis of adult mouse tissues showed that Vbp1 was ubiquitously expressed. In
      situ analysis on several adult tissues showed that in most tissues, transcripts
      were evenly distributed. In brain, eye, kidney and intestine, however, Vbp1 was
      expressed in specific cell types. Moreover, expression of the human VBP1 gene was
      investigated in cerebellum and in various tumours of VHL patients
      encompassinghaemangioblastomas, renal cell carcinomas and pheochromocytomas. In
      all of these tissues, VBP1 was ubiquitously expressed at low levels. However, no
      consistent differences in VBP1 expression levels could be detected between
      tumours and normal tissue. Mapping of the murine Vbp1 gene revealed conserved
      chromosomal localization between mouse and human in a region homologous to human
      Xq28.

PMID- 9931332
TI  - Intra-renal and subcellular distribution of the human chloride channel, CLC-5,
      reveals a pathophysiological basis for Dent's disease.
AB  - Dent's disease, which is a renal tubular disorder characterized by low molecular
      weight proteinuria, hypercalciuria and nephrolithiasis, is associated with
      inactivating mutations of the X-linked chloride channel, CLC-5. However, the
      manner in which a functional loss of CLC-5 leads to such diverse renal
      abnormalities remains to be defined. In order to elucidate this, we performed
      studies to determine the segmental expression of CLC-5 in the human kidney and to
      define its intracellular distribution. We raised and characterized antisera
      against human CLC-5, and identified by immunoblotting an 83 kDa band
      corresponding to CLC-5 in human kidney cortex and medulla. Immunohistochemistry
      revealed CLC-5 expression in the epithelial cells lining the proximal tubules and
      the thick ascending limbs of Henle's loop, and in intercalated cells of the
      collecting ducts. Studies of subcellular human kidney fractions established that
      CLC-5 distribution was associated best with that of Rab4, which is a marker of
      recycling early endosomes. In addition, confocal microscopy studies using the
      proximal tubular cell model of opossum kidney cells, which endogenously expressed
      CLC-5, revealed that CLC-5 co-localized with the albumin-containing endocytic
      vesicles that form part of the receptor-mediated endocytic pathway. Thus, CLC-5
      is expressed at multiple sites in the human nephron and is likely to have a role
      in the receptor-mediated endocytic pathway. Furthermore, the functional loss of
      CLC-5 in the proximal tubules and the thick ascending limbs provides an
      explanation for the occurrences of low molecular weight proteinuria and
      hypercalciuria, respectively. These results help to elucidate further the patho
      physiological basis of the renal tubular defects of Dent's disease.

PMID- 9931331
TI  - A full genome scan for late onset Alzheimer's disease.
AB  - We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD)
      according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years
      using 237 microsatellite markers separated by an average distance of 16.3 cM.
      Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs
      and subsets of 162 ASPs where both members possessed an apolipoprotein E
      (APOE)straightepsilon4 allele and 63 pairs where neither possessed
      anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1
      either in the whole sample, the straightepsilon4-positive or -negative subgroups
      were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two
      peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that
      these findings exceeded those expected by chance, although many are likely to be
      false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS
      2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of
      'suggestive' in that they would be expected to occur by chance once or less per
      genome scan. Several other peaks were only marginally less significant than this,
      in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to
      alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS
      1.77). This is the largest genome scan to date in AD and shows for the first time
      that this is a genetically complex disorder involving several, perhaps many,
      genes in addition to APOE. Moreover, our data will be of interest to those hoping
      to identify positional candidate genes using information emerging from
      neurobiological studies of AD.

PMID- 9931333
TI  - Localization of the APECED protein in distinct nuclear structures.
AB  - Autoimmune-polyendocrinopathy-candidiasis-ecto-dermaldystrophy (APECED) is the
      only systemic autoimmune disease with a monogenic background known so far
      revealing no association with the major histocompatibility complex region. We
      have recently isolated the gene defective in this syndrome and characterized
      several different mutations in individuals with the disorder. The novel gene,
      AIRE, contains a putative bipartite nuclear targeting signal predicting a nuclear
      location of the corresponding protein. The presence of two PHD-type zinc finger
      domains as well as the newly described putative DNA-binding domain, SAND, in the
      amino acid sequence of the APECED protein implies that it may be involved in the
      regulation of gene expression. Using transient expression of AIRE cDNA in
      mammalian cells we demonstrate here the nuclear location of the APECED protein.
      Immunohistochemical staining of transfected cells revealed that most of the
      recombinant 58 kDa APECED protein is present in the form of nuclear dots. By
      double immuno-fluorescence labelling we further show that these APECED-containing
      structures and the previously described PML nuclear bodies are largely non
      overlapping. The AIRE protein was also visualized in multiple human tissues: a
      subset of the cells in thymus, in spleen and in lymph node showed nuclear
      staining with APECED antiserum. Immunofluorescence labelling of peripheral blood
      mononuclear leukocytes also revealed a nuclear body-like staining pattern in a
      fraction of these cells. These data from both in vitro and ex vivo systems,
      together with the predicted structural features of the APECED protein, suggest
      that this protein is most probably involved in the regulation of gene expression.

PMID- 9931334
TI  - Increased expression of the NF2 tumor suppressor gene product, merlin, impairs
      cell motility, adhesionand spreading.
AB  - The neurofibromatosis 2 ( NF2 ) gene product, merlin, is a tumor suppressor
      protein mutated in schwanno-mas and several other tumors. Merlin, which shares
      significant homology with the actin-associated proteins ezrin, radixin and moesin
      (ERM proteins), inhibits cell growth when overexpressed in cell lines. The
      similarities between merlin and ERM proteins suggest that merlin's growth
      regulatory capabilities may be due to alterations in cytoskeletal function. We
      examined this possibility in rat schwannoma cell lines overexpressing wild-type
      merlin isoforms and mutant merlin proteins. We found that overexpression of wild
      type merlin resulted in transient alterations in F-actin organization, cell
      spreading and cell attachment. Merlin overexpression also impaired cell motility
      as measured in an in vitro motility assay. These effects were only observed in
      cells overexpressing a merlin isoform capable of inhibiting cell growth and not
      with mutant merlin molecules (NF2 patient mutations) or a merlin splice variant
      (isoform II) lacking growth-inhibitory activity. These data indicate that merlin
      may function to maintain normal cytoskeletal organization, and suggest that
      merlin's influence on cell growth depends on specific cytoskeletal
      rearrangements.

PMID- 9931335
TI  - AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered
      sub-cellular distribution of mutants lacking the PHD zinc fingers.
AB  - The gene responsible for autoimmune polyendocrino-pathy candidiasis ectodermal
      dystrophy (APECED) recently has been positionally cloned to 21q22.3. This novel
      gene, AIRE, encodes for a predicted 57.7 kDa protein featuring two PHD-type zinc
      fingers shared by other proteins involved in chromatin-mediated tran-scriptional
      regulation. APECED is an autosomal recessive condition characterized by multiple
      polyendocrinopathies, and the typical triad of APECED symptoms includes
      hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous
      candidiasis. The aetiology of APECED is linked directly to mutations within the
      coding region of AIRE. These mutations are predicted to lead to truncated forms
      of the protein lacking at least one of the PHD zinc fingers. In this study, we
      have investigated the sub-cellular localization of AIRE expressed transiently in
      COS cells and fibroblasts. We found that AIRE has a dual nuclear and cytoplasmic
      localization. The wild-type protein is directed to speckled domains in the
      nucleus and also shows co-localization with cytoskeletal filaments. N-terminal
      AIRE fragments deleted for the PHD domain show altered nuclear localization,
      suggesting that the APECED mutations may elicit their primary effects in the
      nucleus.

PMID- 9931336
TI  - Isolation and characterization of human patched 2 (PTCH2), a putative tumour
      suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32.
AB  - Mutations of the human Patched gene ( PTCH ) have been identified in individuals
      with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic
      basal cell carcinomas and medulloblastomas. We have isolated a homologue of this
      tumour suppressor gene and localized it to the short arm of chromosome 1 (1p32.1
      32.3). Patched 2 ( PTCH2 ) comprises 22 coding exons and spans approximately 15
      kb of genomic DNA. The gene encodes a 1203 amino acid putative transmembrane
      protein which is highly homologous to the PTCH product. We have characterized the
      genomic structure of PTCH2 and have used single-stranded conformational
      polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal
      cell carcinomas and in medulloblastomas. To date, we have identified one
      truncating mutation in a medulloblastoma and a change in a splice donor site in a
      basal cell carcinoma, suggesting that the gene plays a role in the development of
      some tumours.

PMID- 9931337
TI  - Leber congenital amaurosis caused by a homozygous mutation (R90W) in the
      homeodomain of the retinal transcription factor CRX: direct evidence for the
      involvement of CRX in the development of photoreceptor function.
AB  - The CRX (cone-rod homeobox) gene is specifically expressed in developing and
      mature photoreceptors and encodes an otd/Otx-like paired homeodomain protein.
      Mutant alleles of the CRX gene have recently been associated with autosomal
      dominant cone-rod dystrophy (CORD) as well as dominant Leber congenital amaurosis
      (LCA). Since LCA is more commonly inherited in an autosomal recessive manner, we
      examined a cohort of recessive LCA patients for CRX mutations. A homozygous
      substitution of arginine (R) at codon 90 by tryptophan (W) was identified in the
      CRX homeodomain of one of the probands who was nearly blind from birth. A group
      of 48 control individuals and 190 previously characterized CORD probands did not
      reveal this sequence change. The mutant CRXR90W homeodomain demonstrated
      decreased binding to the previously identified cis sequence elements in the
      rhodopsin promoter. In transient transfection experiments, the mutant protein
      showed significantly reduced ability to transactivate the rhodopsin promoter, as
      well as lower synergistic activation with the bZIP transcription factor NRL.
      Heterozygosity of the mutant CRX (R90W) allele was detected in both parents and
      in an older sibling. Ophthalmologic examination and electro-retinography revealed
      a subtle abnormality of cone function in both the parents. These data suggest
      that the R90W mutation results in a CRX protein with reduced DNA binding and
      transcriptional regulatory activity and that the subsequent changes in
      photoreceptor gene expression lead to the very early onset severe visual
      impairment in LCA.

PMID- 9931338
TI  - Association of ulcerative colitis with rare VNTR alleles of the human intestinal
      mucin gene, MUC3.
AB  - Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a
      multifactorial disorder with significant genetic influence. Recently, evidence of
      linkage on chromosome 7q near the intestinal mucin gene MUC3 was reported by an
      affected sib-pair analysis. Previous reports indicate a possible mucin
      abnormality in UC patients, but whether genetic differences in a specific mucin
      gene are associated with UC is unknown. Here we analysed polymorphisms of
      variable number of tandem repeats (VNTRs) within this gene using DNAs obtained
      from 243 Japanese (75 patients with UC and 168 controls), and to confirm the
      result we undertook a two-stage examination using 328 Caucasian samples (72 and
      85 with UC in the first and second stages, respectively, and 171 controls). When
      the frequency of patients carrying one or two rare VNTR alleles was compared with
      that of controls, a significant increase was found first in Japanese patients
      (odds ratio 2.72, 95% CI 1.17-6.32, P = 0. 0308). In Caucasians, the odds ratio
      was 2.80 (95% CI 1.36-5.75, P = 0.0079) in the first stage, 2.43 (95% CI 1.20
      4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P = 0.0024) in
      total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P = 0.0001). This
      result suggests that rare alleles of the MUC3 gene may confer genetic
      predisposition to UC.

PMID- 9931339
TI  - Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a
      preponderance of maternally derived deletions.
AB  - The deletion of chromosome 1p36 is a newly recognized, relatively common
      contiguous gene deletion syndrome with a variable phenotype. The clinical
      features have recently been delineated and molecular analysis indicates that the
      prevalence of certain phenotypic features appears to correlate with deletion
      size. Phenotype/genotype comparisons have allowed the assignment of certain
      clinical features to specific deletion intervals, significantly narrowing the
      regions within which to search for candidate genes. We have extensively
      characterized the deletion regions in 30 cases using microsatellite markers and
      fluorescence in situ hybridization analyses. The map order of 28 microsatellite
      markers spanning the deletion region was obtained by a combination of genotypic
      analysis and physical mapping. The deletion region was divided into six intervals
      and breakpoints were found to cluster in mainly two regions. Molecular analysis
      of the deletions showed that two patients had complex re-arrangements; these
      cases shared their distal and proximal breakpoints in the two common breakpoint
      regions. Of the de novo deletions ( n = 28) in whichparental samples were
      available and the analysis was informative ( n = 27), there were significantly
      morematernally derived deletions ( n = 21) than paternally derived deletions ( n
      = 6) (chi1(2) = 8.35, P < 0.0001). Phenotype/genotype correlations and
      refinements of critical regions in our naturally occurring deletion panel have
      delineated specific areas in which to focus the search for the causative genes
      for the features of this syndrome.

PMID- 9931340
TI  - The beta3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the
      mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and
      night blindness.
AB  - Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse
      hypopigmentation mutant pearl. The beta3A subunit of the AP-3 adaptor complex,
      which likely regulates protein trafficking in the trans - Golgi network/endosomal
      compartments, was identified as a candidate for the pearl gene by a
      positional/candidate cloning approach. Mutations, including a large internal
      tandem duplication and a deletion, were identified in two respective pearl
      alleles and are predicted to abrogate function of the beta3A protein.
      Significantly lowered expression of altered beta3A transcripts occurred in kidney
      of both mutant alleles. The several distinct pearl phenotypes suggest novel
      functions for the AP-3 complex in mammals. These experiments also suggest
      mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak
      syndrome and congenital night blindness, for which the pearl mouse is an
      appropriate animal model.

PMID- 9931341
TI  - Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I
      gene in the population: a population-based survey.
AB  - To determine the frequency of familial hypoalphalipoproteinemia in the general
      population due to mutation of the apolipoprotein A-I (apo A-I) gene, we analyzed
      sequence variations in the apo A-I gene. The subjects were 67 children with a low
      high-density lipoprotein (HDL) cholesterol level (</=38 mg/dl, below the fifth
      percentile in the population of this study) who were screened from 1254
      schoolchildren through a school survey. Four different mutations with deleterious
      potential, three frameshifts and one splice site mutation, were identified in
      four of the subjects. The plasma apo A-I levels of the four children with apo A-I
      gene mutations were reduced to approximately half of the normal levels and were
      below the first percentile of the general population distribution (80 mg/dl).
      Thus, the frequency of hypoalphalipoproteinemia due to a mutant apolipoprotein A
      I gene was estimated at 6% (95% CI: 2.4-14. 4%) in the subjects with low HDL
      cholesterol levels and 0.3% (95% CI: 0.1-0.8%) in the Japanese population. This
      suggests that familial hypoalphalipoproteinemia due to apo A-I gene mutations is
      relatively common.

PMID- 9931342
TI  - The chromosome 15 imprinting centre (IC) region has undergone multiple
      duplication events and contains an upstream exon of SNRPN that is deleted in all
      Angelman syndrome patients with an IC microdeletion.
AB  - Imprinting of the Prader-Willi/Angelman syndrome region on human chromosome 15 is
      regulated by an imprinting centre (IC), which spans 5' exons of the gene encoding
      the small nuclear ribonucleoprotein N ( SNRPN ). The IC/ SNRPN transcripts are
      initiated at two alternative start sites, which share a high degree of sequence
      similarity with each other and with two newly identified sites 63 and >700 kb
      further upstream. Three of these sites are hypermethylated on the maternal
      chromosome, whereas one displays an oppositemethylation pattern. We have also
      identified novel splice variants of the IC/ SNRPN transcripts and hitherto
      undetected exons. One of these exons, which we designate u5, is deleted in all
      Angelman syndromepatients with a microdeletion of the IC. We conclude that
      elements of the IC region have undergone multiple duplication events and that u5
      or a sequence close by may play a role in maternal imprinting.

PMID- 9931343
TI  - A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus
      epilepsy of the Lafora type (EPM2).
AB  - Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2;
      McKusick no. 254780) is an autosomal recessive disorder characterized by
      epilepsy, myoclonus, progressive neurological deterioration and glycogen-like
      intracellular inclusion bodies (Lafora bodies). A gene for EPM2 previously has
      been mapped to chromosome 6q23-q25 using linkage analysis and homozygosity
      mapping. Here we report the positional cloning of the 6q EPM2 gene. A
      microdeletion within the EPM2 critical region, present inhomozygosis in an
      affected individual, was found to disrupt a novel gene encoding a putative
      protein tyrosine phosphatase (PTPase). The gene, denoted EPM2, presents
      alternative splicing in the 5' and 3' end regions. Mutational analysis revealed
      that EPM2 patients are homozygous for loss-of-function mutations in EPM2. These
      findings suggest that Lafora disease results from the mutational inactivation of
      a PTPase activity that may be important in the control of glycogen metabolism.

PMID- 9931344
TI  - A Pro51Ser mutation in the COCH gene is associated with late onset autosomal
      dominant progressive sensorineural hearing loss with vestibular defects.
AB  - We analysed a Dutch family with autosomal dominant non-syndromic progressive
      sensorineural hearing loss and mapped the underlying gene defect by genetic
      linkage analysis to a 11.0 cM region overlapping the DFNA9 interval on chromosome
      14q12-q13. Clinically, the Dutch family differs from the original DFNA9 family by
      a later age at onset and a more clearly established vestibular impairment. A gene
      that is highly and specifically expressed in the human fetal cochlea and
      vestibule, COCH (previously described as Coch5B2 ), was mapped to the DFNA9
      critical region. Sequence analysis revealed a 208C-->T mutation in the COCH gene,
      resulting in a Pro51Ser substitution in the predicted protein in all affected
      individuals of the family but not in unaffected family members and 200 control
      individuals. The same mutation was also identified in three apparently unrelated
      families with a similar phenotype, suggesting the presence of a Dutch founder
      mutation. The function of COCH is unknown but several characteristics of the
      protein point to a structural role in the extracellular matrix. The mutant serine
      at position 51 is situated between cysteines and possibly interferes with proper
      COCH protein folding or its interaction with extracellular matrix proteins.

PMID- 9931345
TI  - Thiopurine methyltransferase alleles in British and Ghanaian populations.
AB  - Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine
      drugs such as 6-mercapto-purine, 6-thioguanine and azathioprine. TPMT activity is
      inherited as an autosomal co-dominant trait, and several mutations in the TPMT
      gene have been identified which correlate with a low activity phenotype. Although
      ethnic differences in TPMT activity have been described, population frequency
      analysis of TPMT alleles has not been well defined in different ethnic groups.
      The frequency of four allelic variants of the TPMT gene, TPMT*2, TPMT*3A, TPMT*3B
      and TPMT*3C were compared in British Caucasian (n = 199) and Ghanaian (n = 217)
      populations using PCR-RFLP and allele-specific PCR-based assays. TPMT*3C was
      found in 14.8% of Ghanaians (31 heterozygotes, one homozygote). The TPMT*2,
      TPMT*3A and TPMT*3B alleles were not detected in any of the Ghanaian samples
      analysed. In contrast, 10.1% of British subjects had variant alleles, consisting
      of TPMT*2 (n = 2), TPMT*3A (n = 17) and TPMT*3C  (n = 1) alleles. The frequencies
      of mutant alleles in this study were 5.3 and 7.6% in British Caucasians and
      Ghanaians, respectively. Among Ghanaian tribes, Ewe subjects had a lower
      frequency of mutant alleles (5.9%) than Ga (13.2%) or Fanti (11.6%), although
      this did not reach statistical significance. This study provides the first
      analysis of TPMT mutant allele frequency in an African population and indicates
      that, unlike Caucasians, TPMT*3C is the most common allele in African subjects.

PMID- 9931346
TI  - Polymorphism of the thiopurine S-methyltransferase gene in African-Americans.
AB  - The molecular basis for the genetic polymorphism of thiopurine S 
      methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to
      be elucidated in African populations. In the current study, we determined TPMT
      genotypes in a population of 248 African-Americans and compared it with allele
      frequencies in 282 Caucasian Americans. TPMT genotype was determined in all
      individuals with TPMT activity indicative of a heterozygous genotype (</=10.1
      U/ml pRBC, n = 23African-Americans, n = 21 Caucasians) and a control group with
      TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n =
      23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the
      high activity control groups. The overall mutant allele frequencies were similar
      in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively).
      However, while TPMT*3C was the most prevalent mutant allele in African-Americans
      (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in
      Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in
      African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most
      prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele (
      TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino
      acid change at codon 215 (Arg-->His), was found in one African-American with
      intermediate activity. These data indicate that the same TPMT mutant alleles are
      found in American black and white populations, but that the predominant mutant
      alleles differ in these two ethnic groups.

PMID- 9931347
TI  - H4 acetylation, XIST RNA and replication timing are coincident and define
      x;autosome boundaries in two abnormal X chromosomes.
AB  - The inactive X (Xi) differs from its active homologue (Xa) in a number of ways,
      including increased methylation of CpG islands, replication late in S phase,
      underacetylation of histone H4 and association with XIST RNA. Global changes in
      DNA methylation occur relatively late in development, but the other properties
      all change during or shortly after the establishment of Xi and may play a role in
      the mechanism by which an inactive chromatin conformation spreads across most of
      the chromosome. In the present report, we use two human X;autosome translocation
      chromosomes to study the spreading of inactive X chromatin across X;autosome
      boundaries. In one of these chromosomes, t(X;6), Xp distal to p11.2 is replaced
      by 6p21.1-6pter and, in the other, ins(X;16), a small fragment derived from 16p13
      is inserted into the distal third of Xq. In lymphoid cells from patients carrying
      these translocations in an unbalanced form, Xi was shown by HUMARA assay to be
      derived exclusively [t(X:6)] or predominantly [ins (X;16)] from the derived X
      chromosome. We used a combination of immunolabelling and RNA/DNA fluorescence in
      situ hybridization to define the distribution of XIST RNA, deacetylated H4 and
      late-replicating DNA across the two derived X chromosomes in inactive form.
      Within the limits of the cytogenetic techniques employed, the results show
      complete coincidence of these three parameters, with all three being excluded
      from the autosomal component of the derived X chromosome.

PMID- 9931348
TI  - Intracellular neuronal calcium sensor proteins: a family of EF-hand calcium
      binding proteins in search of a function.
AB  - Intracellular neuronal calcium sensors (NCS) constitute a rapidly growing family
      of calcium-binding proteins which belong to the superfamily of EF-hand proteins.
      The NCS family includes as subgroups the recoverins and GCAPs (guanylyl cyclase
      activating proteins), which are primarily expressed in retinal photoreceptor
      cells, and the frequenins and VILIPs (visinin-like proteins), which are widely
      but differentially expressed in the nervous system. In this review the recent
      developments in elucidating the functional activities of NCS proteins on signal
      transduction pathways in neurons are surveyed and discussed. We will focus our
      attention on calcium-dependent membrane association by the so-called calcium
      myristoyl switch as a possible mechanism of signal transduction and on the roles
      of NCS proteins in intraneuronal signaling cascades, which are best studied in
      the visual and olfactory systems.

PMID- 9931349
TI  - Peripheral synapses at identifiable mechanosensory neurons in the spider
      Cupiennius salei: synapsin-like immunoreactivity.
AB  - Indirect immunocytochemical tests were used at the light- and electron
      microscopic levels to investigate peripheral chemical synapses in identified
      sensory neurons of two types of cuticular mechanosensors in the spider Cupiennius
      salei Keys.: (1) in the lyriform slit-sense organ VS-3 (comprising 7-8 cuticular
      slits, each innervated by 2 bipolar sensory neurons) and (2) in tactile hair
      sensilla (each supplied with 3 bipolar sensory cells). All these neurons are
      mechanosensitive. Application of a monoclonal antibody against Drosophila
      synapsin revealed clear punctate immunofluorescence in whole-mount preparations
      of both mechanoreceptor types. The size and overall distribution of
      immunoreactive puncta suggested that these were labeled presynaptic sites.
      Immunofluorescent puncta were 0.5-6.8 micrometer long and located 0.5-6.6
      micrometer apart from each other. They were concentrated at the initial axon
      segments of the sensory neurons, while the somata and the dendritic regions
      showed fewer puncta. Western blot analysis with the same synapsin antibody
      against samples of spider sensory hypodermis and against samples from the central
      nervous system revealed a characteristic doublet band at 72 kDa and 75 kDa,
      corresponding to the apparent molecular mass of synapsin in Drosophila and in
      mammals. Conventional transmissionelectron-microscopic staining demonstrated that
      numerous chemical synapses (with at least 2 vesicle types) were present at these
      mechanosensory neurons and their surrounding glial sheath. The distribution of
      these synapses corresponded to our immunofluorescence results. Ultrastructural
      examination of anti-synapsin-stained neurons confirmed that reaction product was
      associated with synaptic vesicles. We assume that the peripheral synaptic
      contacts originate from efferents that could exert a complex modulatory influence
      on mechanosensory activity.

PMID- 9931350
TI  - Nerve growth factor receptor signaling in proliferation of normal adult rat
      chromaffin cells.
AB  - Adult rat chromaffin cells may proliferate or extend neurites when stimulated by
      nerve growth factor (NGF) but their response is predominantly proliferative,
      making them a unique model for studying how mitogenic specificity is achieved. We
      examined contributions of the NGF receptors trk and p75 and of the major NGF
      signaling pathways to proliferation versus neurite outgrowth. The type of initial
      NGF response does not correlate with intensity of immunoreactivity for trk or
      p75. However, proliferation is initiated at lower NGF concentrations than neurite
      outgrowth, suggesting that it requires a less intense signal. Mitogenic
      cooperativity between receptors at low NGF concentrations is suggested by
      inhibitory effects of p75-blocking antibodies, but responses to trk-agonist
      antibody indicate that trk activation alone can induce proliferation. NGF-induced
      phosphorylation of ras-mediated mitogen-activated protein kinases (MAPK) Erk1 and
      Erk2 is as prolonged in normal chromaffin cells as in PC12 cells, where NGF is
      neuritogenic. Trk-agonist antibody, which is as mitogenic as NGF but less
      neuritogenic, causes equally prolonged but less intense ERK phosphorylation. The
      MAPK kinase(MEK-1) inhibitor PD98059 partially inhibits Erk phosphorylation and
      does not inhibit chromaffin cell proliferation, while depolarization selectively
      inhibits proliferation without blocking Erk phosphorylation. Proliferation is
      markedly reduced by the phosphoinositol-3 (PI-3) kinase inhibitor LY294002 while
      downregulation of protein kinase C (PKC) causes no change. These findings suggest
      that low-level, rather than short-duration, stimulation of NGF signaling pathways
      causes NGF to be mitogenic. Ras-mediated MAPK activation may be more critical in
      neurite outgrowth than in proliferation and PI-3 kinase may be the major
      mitogenic determinant.

PMID- 9931351
TI  - Developmental expression of galanin-like immunoreactivity by members of the avian
      sympathoadrenal cell lineage.
AB  - The developmental coexpression of galanin-like immunoreactivity with the
      catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) was studied in the
      avian embryo sympathoadrenal system using double-labeling immunocytochemistry.
      Galanin-like immunoreactivity is expressed by various catecholaminergic cell
      populations, namely sympathoblasts, chromaffin and small intensely fluorescent
      (SIF) cells, but not by principal neurons of the paravertebral sympathetic
      ganglia. Both galanin and somatostatin immunoreactivities are coexpressed in the
      adrenal and sympathetic ganglion primordia by the neural precursors, but the
      subsequent expression pattern of both peptides differs. Our results support the
      hypothesis that early sympathoblasts express a large repertoire of neuroactive
      substances and that the expression of these becomes restricted during further
      development as the sympathoblasts become principal neurons.

PMID- 9931352
TI  - Vagal afferents from the uterus and cervix provide direct connections to the
      brainstem.
AB  - Previous anatomical studies demonstrated vagal innervation to the ovary and
      distal colon and suggested the vagus nerve has uterine inputs. Recent behavioral
      and physiological evidence indicated that the vagus nerves conduct sensory
      information from the uterus to the brainstem. The present study was undertaken to
      identify vagal sensory connections to the uterus. Retrograde tracers, Fluorogold
      and pseudorabies virus were injected into the uterus and cervix. DiI, an
      anterograde tracer, was injected into the nodose ganglia. Neurectomies involving
      the pelvic, hypogastric, ovarian and abdominal vagus nerves were performed, and
      then uterine whole-mounts examined for sensory nerves containing calcitonin gene
      related peptide. Nodose ganglia and caudal brainstem sections were examined for
      the presence of estrogen receptor-containing neurons in "vagal locales." Labeling
      of uterine-related neurons in the nodose ganglia (Fluorogold and pseudorabies
      virus) and in the brainstem nuclei (pseudorabies virus) was obtained. DiI-labeled
      nerve fibers occurred near uterine horn and uterine cervical blood vessels, in
      the myometrium, and in paracervical ganglia. Rats with vagal, pelvic, hypogastric
      and ovarian neurectomies exhibited a marked decrease in calcitonin gene-related
      peptide-immunoreactive nerves in the uterus relative to rats with pelvic,
      hypogastric, and ovarian neurectomies with intact vagus nerves. Neurons in the
      nodose ganglia and nucleus tractus solitarius were immunoreactive for estrogen
      receptors. These results demonstrated: (1) the vagus nerves serve as connections
      between the uterus and CNS, (2) the nodose ganglia contain uterine-related vagal
      afferent neuron cell bodies, and (3) neurons in vagal locales contain estrogen
      receptors.

PMID- 9931353
TI  - Axonal and dendritic transport in Purkinje cells of cerebellar slice cultures
      studied by microinjection of horseradish peroxidase.
AB  - Axonal and dendritic transport in single Purkinje neurons of cerebellar slice
      cultures was quantified as single transport distances. Examination of the cells
      within a vital tissue was regarded as being an approach to the in situ condition.
      The Purkinje cells were organotypically integrated in the in vitro tissues and
      extended long axonal projections connecting synapses to the target neurons. The
      tracer horseradish peroxidase (HRP) was applied via microinjection to the somata
      of the Purkinje cells and the injected neurons were incubated thereafter for
      defined time-intervals. The tracer was transported anterogradely into the neuron
      processes. The measurements on both the axonal and the dendritic transport of
      microinjected HRP revealed continuous transportation with increasing times of
      postincubation. This transport was reduced by the use of microtubule
      depolymerizing drugs. The axonal transport of the tracer was either retarded in
      colchicine-treated cells or continuously reduced for up to 50% in vinblastine
      treated neurons. Thus, a correlation of axonal transport to the microtubules was
      demonstrated. The dendrites were filled with the tracer after 60 min of
      postincubation. Dendritic transport was reduced by the use of vinblastine, and
      not significantly by colchicine. The results strongly support the dependence of
      neuronal transport on microtubules as a component of the cytoskeleton.

PMID- 9931354
TI  - Evidence of decreased adhesion between the neural retina and retinal pigmented
      epithelium of the Mitfvit (vitiligo) mutant mouse.
AB  - In order for the retina to function properly, photoreceptor cell outer segments
      must be in contact with the adjacent retinal pigmented epithelium (RPE). A mouse
      model homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene
      manifests disruption of the outer segment/RPE interdigitation and demonstrates
      progressive loss of the photoreceptor cells. The mouse nevertheless has near
      normal levels of rhodopsin for many weeks and it is not known whether there is an
      in vivo loss of adhesion or whether the disruption is visible following tissue
      processing for histology. To assess this, a mechanical separation experiment was
      performed in which neural retinas were peeled free from the RPE and examined for
      the amount of pigment adherent to them. The peeling experiment indicated that
      control neural retinas retained significant amounts of adherent pigment at all
      ages examined. Neural retinas of mutant mice at age 2 weeks demonstrated adherent
      pigment, but older animals retained minimal pigment. Scanning electron microscopy
      indicated that the RPE cells of control mice were markedly damaged upon peeling
      and displayed different planes of cleavage, whereas those of mutants showed
      minimal cellular damage upon peeling, suggestive of decreased adhesion. A
      recombination experiment revealed that the mutant RPE/eyecup could reappose
      mutant and control retinas under in vitro conditions, suggesting that RPE fluid
      transport abilities were intact. The data provide the first direct experimental
      evidence that the Mitfvit mutant mouse has a naturally occurring retinal
      detachment and hence support its value as a model for studies of retina/RPE
      adhesion.

PMID- 9931355
TI  - Immunoultrastructural expression of intercellular adhesion molecule-1 in
      endothelial cell vesiculotubular structures and vesiculovacuolar organelles in
      blood-brain barrier development and injury.
AB  - Blood vessels from the vasculature of mouse brains during postnatal development
      and from human brain tumors (hemangiomas) removed at biopsy were examined
      immunocytochemically by transmission electron microscopy (TEM) or high-voltage
      transmission electron microscopy (HVEM) to determine the expression of
      intercellular adhesion molecule-1 (ICAM-1). In the mouse brains, ICAM-1 was shown
      to be initially expressed on the luminal and abluminal endothelial cell (EC)
      surfaces on day 3 after birth. ICAM-1 intensity increased on the luminal EC
      surfaces and labeled vesiculotubular profiles (VTS, defined in the present
      report) between days 5 and 7. After 2 weeks and at 6 months after birth, ICAM-1
      labeling was weak or absent on the luminal EC surfaces. The hemangiomas presented
      a strong ICAM-1 reaction product on the luminal EC surfaces of small and large
      blood vessels associated with the VTS, with a weaker labeling of the abluminal or
      adventitial aspects of larger blood vessels. TEM of vesiculovacuolar structures
      (VVOs) within ECs from arteries and veins also demonstrated reaction product for
      ICAM-1 labeling. Three-dimensional stereo-pair images in the HVEM enhanced the
      visualization of gold particles that were attached to the inner-delimiting
      membrane surfaces of EC VTS, and VVOs, respectively. These observations raise the
      possibility that the neonatal leukocytes and tumor cells may utilize these
      endothelial structures as a route across the developing and injured blood-brain
      barrier (BBB).

PMID- 9931356
TI  - Low-density lipoproteins modulate endothelial cells to secrete endothelin-1 in a
      polarized pattern: a study using a culture model system simulating arterial
      intima.
AB  - We investigated the structural and functional properties of human umbilical vein
      endothelial cells (HUVECs) cultured on a two-chamber culture model system using
      an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs
      cultured on the model system exhibited several features similar to those of in
      vivo vessels, including formation of the intercellular junctional devices and
      expression of tight junction-associated protein ZO-1 and adherence junction
      associated protein alpha-catenin. Furthermore, we found that HUVECs had a
      property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount
      of synthesized ET-1 was found in the lower well, designated as the basal side.
      When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or
      oxidized LDLs (oxLDLs) at a concentration of 100 microgram/ml, ET-1 secretion was
      significantly increased, dependent on the cell side (apical vs basal) on which
      the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side,
      the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL)
      and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on
      the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side,
      however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side,
      with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and
      oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1
      secretion from HUVECs on the opposite side of the well on which HDLs were loaded;
      there was a 57% decrease on the basal side when HDLs were loaded on the apical
      side, and a 46% decrease on the apical side when loaded on the basal side. These
      results indicate that modulation of ET-1 secretion from ECs by lipoproteins is
      virtually dependent on the place (apical vs basal) where these proteins are
      present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a
      polarized pattern suggests that ET-1 may be involved in pathophysiological
      processes such as atherogenesis.

PMID- 9931357
TI  - Caveolin and its cellular and subcellular immunolocalisation in lung alveolar
      epithelium: implications for alveolar epithelial type I cell function.
AB  - Caveolae are flask-shaped invaginations of the plasmalemma which pinch off to
      form discrete vesicles within the cell cytoplasm. Biochemically, caveolae may be
      distinguished by the presence of a protein, caveolin, that is the principal
      component of filaments constituting their striated cytoplasmic coat. Squamous
      alveolar epithelial type I (ATI) cells, comprising approximately 95% of the
      surface area of lung alveolar epithelium, possess numerous plasmalemmal
      invaginations and cytoplasmic vesicles ultrastructurally indicative of caveolae.
      However, an ultrastructural appearance does not universally imply the biochemical
      presence of caveolin. This immunocytochemical study has utilised a novel
      application of confocal laser scanning and electron microscopy unequivocally to
      localise caveolin-1 to ATI cells. Further, cytoplasmic vesicles and flask-shaped
      membrane invaginations in the ATI cell were morphologically identified whose
      membranes were decorated with anti-caveolin-1 immunogold label. Coexistent with
      this, however, in both ATI and capillary endothelial cells could be seen membrane
      invaginations morphologically characteristic of caveolae, but which lacked
      associated caveolin immunogold label. This could reflect a true biochemical
      heterogeneity in populations of morphologically similar plasmalemmal
      invaginations or an antigen threshold requirement for labelling. The cuboidal
      alveolar epithelial type II cell (ATII) also displayed specific label for
      caveolin-1 but with no ultrastructural evidence for the formation of caveolae.
      The biochemical association of caveolin with ATI cell vesicles has broad
      implications for the assignment and further study of ATI cell function.

PMID- 9931358
TI  - Effects of rhizopodin and latrunculin B on the morphology and on the actin
      cytoskeleton of mammalian cells.
AB  - The effects of the novel myxobacterial compound rhizopodin on mammalian cells
      were studied and compared with those of latrunculin B. Both substances induced
      adherently growing L929 mouse fibroblasts and PtK2 potoroo kidney cells to
      produce long, narrow, branched extensions or runners. Rhizopodin was more
      efficient than latrunculin B in that respect (minimal inhibitory concentration
      with L929 cells 5 nM vs 50 nM), and, in contrast to latrunculin B, its effects
      were permanent. Rhizopodin-treated cells became much larger than normal cells and
      were multinucleate, yet stayed alive and biochemically active for several weeks.
      Latrunculin B-treated cells returned to a quasi-normal state within 3-4 days. But
      latrunculin B acted faster, with the first effects becoming visible almost
      immediately upon the addition of the drug, while the first rhizopodin effects
      were seen 10 min later. Both substances caused reorganization of the actin
      cytoskeleton. When 100 nM rhizopodin was added to PtK2 cells, the stress fibers
      began to decay after just 10 min and had disappeared completely after about 3 h.
      Later there was a gradual restitution of F-actin. Long F-actin fibers were seen
      within the runners, and only there; in fact, these fibers may be responsible for
      the development and extension of the runners. The microtubuli network adjusted
      itself to the new cell morphology, but was not directly impaired by the compound.

PMID- 9931359
TI  - Effects of reserpine on ECL-cell ultrastructure and histamine
      compartmentalization in the rat stomach.
AB  - The histamine-storing ECL cells in the stomach play a key role in the control of
      acid secretion. They contain granules, secretory vesicles and microvesicles, and
      sustained gastrin stimulation results in the additional formation of vacuoles and
      lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2
      (VMAT-2), which can be inhibited by reserpine. The present study examines the
      effect of reserpine on ECL-cell ultrastructure and histamine
      compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given
      twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by
      subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine
      injection and continuing for 4 days when the rats were killed. At this stage,
      histamine in the oxyntic mucosa was unaffected by reserpine but elevated by
      gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell
      histamine in control and gastrin-treated rats to be localized in cytoplasmic
      organelles (e.g., secretory vesicles). After treatment with reserpine alone or
      reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric
      analysis (electron microscopy) of ECL cells showed reserpine to increase the
      number, size and volume density of the granules and to reduce the size and volume
      density of the secretory vesicles. Gastrin reduced the number and volume density
      of granules and secretory vesicles, increased the number and volume density of
      microvesicles and caused vacuoles and lipofuscin bodies to appear.
      Reserpine+gastrin increased the number, volume density and size of the granules.
      Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and
      microvesicles, but did not prevent the development of lipofuscin. Our findings
      are in line with the views: (1) that preformed cytosolic histamine is taken up by
      granules/secretory vesicles via VMAT-2, that histamine is instrumental in the
      transformation of granules into secretory vesicles and in their consequent
      enlargement and (2) that vacuoles are formed by the fusion of large secretory
      vesicles.

PMID- 9931360
TI  - Immunocytochemical detection of mitochondria-rich cells in the brood pouch
      epithelium of the pipefish, Syngnathus schlegeli: structural comparison with
      mitochondria-rich cells in the gills and larval epidermis.
AB  - The brood pouch of the male pipefish (Syngnathus schlegeli) is a ventral organ
      located on the tail, with the anterior region closely associated with the genital
      pore. The embryos in the pouch are attached to highly vascularized placenta-like
      tissue which seals the pouch folds from inside during incubation. The epithelium
      of the placenta-like tissue consists of mitochondria-rich cells (MRCs) and
      pavement cells. Differences in MRC morphology in the brood pouch epithelium, the
      gills and the larval epidermis of the pipefish were examined by light and
      electron microscopy. Transmission electron microscopy revealed that the MRCs in
      the brood pouch and the gills shared common characteristics: the presence of
      numerous mitochondria packed among a well-developed tubular system and the close
      association of the basal parts with the capillaries running underneath the
      epithelia. The size of the apical opening of the elongate, flask-shaped brood
      pouch MRC was about one-tenth that of the apical pit of the gill MRC. The gill
      and larval epidermal MRCs formed a multicellular complex, in contrast to solitary
      brood pouch MRCs. The brood pouch MRCs were intensively stained by
      immunocytochemistry with an antiserum specific for Na+,K+-ATPase. The Na+
      concentrations in the brood pouch were maintained near those in the serum rather
      than seawater during incubation. We conclude that the brood pouch MRCs function
      as an ion-transporting cell, absorbing ions from the brood pouch lumen, perhaps
      to protect the embryos from the hyperosmotic environment.

PMID- 9931361
TI  - The distribution and ultrastructure of class II MHC-positive cells in human
      dental pulp.
AB  - The distribution and ultrastructure of class II major histocompatibility complex
      (MHC)-positive cells were investigated in human dental pulp, employing
      immunohistochemistry using an anti-human leukocyte antigen (HLA)-DR-monoclonal
      antibody. HLA-DR-immunopositive cells, appearing spindle-like or dendritic in
      profile, were densely distributed throughout the dental pulp. Under the electron
      microscope, these cells exhibited various sizes of vesicles containing clear or
      opaque contents, multivesicular bodies and characteristic fine tubulovesicular
      structures in their cytoplasm. Some reactive cells possessed coated pits and
      vesicles including electron-dense materials, indicating an active endocytosis. At
      the periphery of the pulp tissue, the HLA-DR-immunopositive cells were
      predominantly situated in the subodontoblastic layer, with some located in the
      odontoblast layer and/or predentin and extending their cytoplasmic processes into
      the dentinal tubules. Cell processes of these cells occasionally made contact
      with several odontoblast processes in the same way as the nerve fibers in the
      predentin. These cells never contained the typical phagosomes frequently observed
      in the HLA-DR-immunoreactive macrophages in the subodontoblastic layer and the
      pulp core. The results suggest that the HLA-DR-immunopositive cells in the
      odontoblast layer and/or predentin have some regulatory function on the
      odontoblasts under physiological conditions, in addition to their involvement in
      the initial defense reaction after tooth injury.

PMID- 9931362
TI  - Periviscerokinin-like immunoreactivity in the nervous system of the American
      cockroach.
AB  - A highly specific polyclonal antiserum has been raised against periviscerokinin,
      the first neuropeptide isolated from the perisympathetic organs of insects
      (Predel et al. 1995). In this study, two different neuronal systems with
      periviscerokinin-like immunoreactivity were distinguished in the central nervous
      system of the American cockroach: (1) An intrinsic neuronal network, restricted
      to the head-thoracic region, was formed by intersegmental projecting neurons of
      the brain, suboesophageal ganglion and metathoracic ganglion. In addition, groups
      of local interneurons occurred in the proto- and tritocerebrum. (2) A typical
      neurohormonal system was stained exclusively in the abdomen; it was represented
      by abdominal perisympathetic organs which were supplied by three cell clusters
      located in each unfused abdominal ganglion. As revealed by nickel backfills, most
      neurons with axons entering the perisympathetic organs contained a
      periviscerokinin-like peptide. Immunoreactive fibres left the perisympathetic
      organs peripherally, innervated the hyperneural muscle and ran via the link
      nerves/segmental nerves to the heart and segmental vessels. All visceral muscles
      innervated by periviscerokinin-immunoreactive fibres were shown to be sensitive
      to periviscerokinin, whereas the hindgut gave no specific response to this
      peptide.

PMID- 9931363
TI  - A comparative immunocytochemical study of the hyperglycaemic, moult-inhibiting
      and vitellogenesis-inhibiting neurohormone family in three species of decapod
      crustacea.
AB  - Eyestalks of the palinuran species Jasus lalandii and Panulirus homarus, and the
      brachyuran species Carcinus maenas, were examined with antisera raised against
      purified crustacean hyperglycaemic hormone (cHH) of the astacidean species
      Homarus americanus and Procambarus bouvieri, as well as the brachyuran species
      Cancer pagurus. Other antisera used in this investigation were raised against
      purified moult-inhibiting hormone (MIH) of C. pagurus and vitellogenesis
      inhibiting hormone (VIH) of H. americanus. Positive immunoreactions to all the
      antisera were localised in perikarya of the X-organ and the axon terminals in the
      sinus gland of all the crustaceans investigated. These results illustrate the
      existence of an immunological similarity, detectable at the immunocytochemical
      level, between the cHH/MIH/VIH neurohormones of the Astacidae, Palinura and
      Brachyura infraorders. Furthermore, results from consecutive tissue sections
      indicate that cHH, MIH and VIH are co-localised in a subpopulation of X-organ
      neurons.

PMID- 9931364
TI  - The controversy about spinal neuronal nitric oxide synthase: under which
      conditions is it up- or downregulated?
AB  - In recent years, the regulation of the synthesis of nitric oxide (NO) in the
      central nervous system has attracted much interest because it has been shown that
      NO is involved in a wide variety of functions such as neuroprotection,
      neurotoxicity, neurotransmission, and neuroplasticity under physiological and
      pathophysiological conditions. However, the use of different detection techniques
      for neuronal nitric oxide synthase (nNOS), different animal species, and
      different experimental lesions has led to contradictory results concerning the
      direction of changes in spinal nNOS expression. This paper summarizes the
      available data on the expression on nNOS in the spinal cord under physiological
      and pathological conditions and tries to extract some of the basic mechanisms
      that underlie neuronal up- or downregulation of this enzyme. Wherever possible,
      results obtained with the NADPH-dependent diaphorase reaction are also included
      for reasons of comparison. The main conclusion is that changes in spinal nNOS
      expression critically depend on the type of afferent fibres activated by a
      specific lesion as well as the intensity and duration of input to the spinal
      cord. This input may be further modified by supraspinal influences. Thus the
      exact composition of these factors, which is undoubtfully highly variable between
      different experimental models, appears to determine whether the spinal NO system
      responds with an up- or downregulation of nNOS expression or in a bidirectional
      way. With regard to the diaphorase reaction it is becoming increasingly clear
      that under pathological conditions data obtained with this reaction differ
      markedly from those obtained with immunohistochemical visualization of nNOS.

PMID- 9931366
TI  - Cellular localization and distribution of glucocorticoid receptor
      immunoreactivity and the expression of glucocorticoid receptor messenger RNA in
      rat pituitary gland. A combined double immunohistochemistry study and in situ
      hybridization histochemical analysis.
AB  - By means of double immunohistochemical techniques and a nonradioisotopic in situ
      hybridization method, we determined the colocalization pattern of glucocorticoid
      receptor (GR) and pituitary hormones and the GR messenger RNA (mRNA) expression
      in the pituitaries of Wistar adult male rats. Immunoreactivity for GR was
      detected in the nuclei of cells in the anterior and posterior pituitary. Double
      immunohistochemistry revealed that the colocalization of GR and anterior
      pituitary hormones occurred in almost 99% of the growth hormone (GH)-producing
      cells and adrenocorticotropic hormone (ACTH)-producing cells, and in 67% of the
      thyroid stimulating hormone (TSH)-producing cells. Almost all of the
      folliculostellate cells (93%), marginal layer cells (94%) in the anterior
      pituitary, and pituicytes (96%) in the posterior pituitary immunostained for S100
      protein antibody were also immunostained with GR. GR mRNA was abundant in the
      cytoplasm of anterior and intermediate pituitary cells but scattered sparsely in
      that of the posterior pituitary. These results suggest that glucocorticoids
      directly influence certain pituitary cells in order to regulate cell function,
      including the synthesis and/or secretion of hormones.

PMID- 9931365
TI  - Induction of epithelio-mesenchymal transformation of quail embryonic neural cells
      by inhibition of atypical protein kinase-C.
AB  - Epithelio-mesenchymal transition, which involves the re-organisation of cell-cell
      adhesion molecules and the actin cytoskeleton, can be induced in embryonic neural
      epithelium in vitro by protein kinase-C inhibitors. A non-inhibitory analogue,
      BIM V, and potent inhibitors of other kinases are not active. This suggests a
      central role for C-kinases, although the powerful specific C-kinase inhibitors
      BIM I and Ro 31-8220 show lower than expected activity. Co-inhibition by several
      kinases is unlikely to account for this, since no potentiation occurs when these
      are combined with potent inhibitors of other kinases. BIM I and Ro 31-8220
      strongly inhibit only conventional calcium-regulated C-kinases; this and the lack
      of effect of TMB-8, which inhibits calcium release, suggests that novel and/or
      atypical isoforms are involved. Various potentiators and activators of
      conventional and novel C-kinases have no obvious effect alone and fail to reduce
      the effect of staurosporine, suggesting that atypical C-kinases are critical. The
      presence of C-kinase isoforms in the E2 embryonic neural tissues has been probed
      on Western blots, revealing immunoreactivity for the atypical isoforms iota (or
      lambda) and zeta and the alpha, gamma, epsilon and mu isoforms. Immunofluorecent
      localisation on sections of embryos has shown the widespread distribution of
      conventional and novel isoforms but only the atypical isoforms lambda and zeta
      are enriched at the apical margins of the neural and other epithelia; they
      overlap with the cell-cell adhesion molecule N-cadherin and with F-actin. Thus,
      epithelio-mesenchymal transition in the embryonic neural epithelium in vitro is
      induced by inhibiting protein kinase activity, probably via an atypical protein
      kinase-C; atypical protein kinase-C isoforms are present in the tissue at the
      appropriate developmental stage and subcellular site in cells capable of
      epithelio-mesenchymal transition.

PMID- 9931367
TI  - Cholinergic and GABAergic neuronal elements in the pineal organ of lampreys, and
      tract-tracing observations of differential connections of pinealofugal neurons.
AB  - The putative cholinergic and GABAergic elements of the pineal organ of lampreys
      were investigated with immunocytochemistry to choline acetyltransferase (ChAT)
      and gamma-aminobutyric acid (GABA), and by acetylcholinesterase (AChE)
      histochemistry. For comparison we also carried out immunocytochemistry to
      serotonin (5-HT) and a tract-tracing investigation of the two types of projecting
      cells, i. e., ganglion cells and long-axon photoreceptors. Most photoreceptors
      were ChAT-immunoreactive (ChAT-ir) and AChE-positive, while ganglion cells and
      the pineal tract were ChAT-negative and AChE-negative or only faintly positive.
      These results strongly suggest the presence of a cholinergic system of
      photoreceptors in the lamprey pineal organ. GABA-ir fibers that appear to
      originate from faintly to moderately stained ganglion cells were observed in the
      pineal stalk. Immunocytochemistry to 5-HT indicated the presence of two types of
      5-HT-ir cells, bipolar cells and ganglion-like cells. The connections of the
      ganglion cells and long-axon photoreceptors were also studied by application of
      DiI to the pineal stalk in fixed brains or of biotinylated dextran amine (BDA) to
      one of the main targets of pinealofugal fibers (optic tectum or mesencephalic
      tegmentum) in isolated brains in vitro. Some long-axon photoreceptors and
      ganglion cells were labeled from the optic tectum. However, BDA application to
      the tegmentum exclusively labeled ganglion cells in the pineal organ. These
      results indicate that the two morphological types of afferent pineal neuron have
      different projections. No labeled cells were observed in the parapineal organ in
      BDA experiments, indicating that this organ and the pineal organ are involved in
      different neural circuits.

PMID- 9931368
TI  - Arginine vasotocin mRNA revealed by in situ hybridization in bovine pineal gland
      cells.
AB  - Arginine vasopressin (AVP) is the main antidiuretic hormone in mammals and
      arginine vasotocin (AVT) in submammalian vertebrates. The possibility that the
      genetic material encoding AVT is maintained in mammals is controversial. In this
      study, we investigated by radioactive in situ hybridization the possible presence
      of the mRNA encoding AVP and AVT, and using immunocytochemistry the presence of
      structures immunoreactive for AVP and AVT in the bovine pineal gland. In situ
      hybridization was performed by use of 35S-labelled oligoprobes.
      Immunocytochemistry was performed using specific polyclonal rabbit antibodies and
      the avidin-biotin-complex method. In situ hybridization revealed positive signals
      for both AVP mRNA and AVT mRNA in a few cells scattered throughout the pineal
      body. Immunocytochemistry revealed thin AVP-immunoreactive fibres in the pineal
      stalk and the pineal gland. It also revealed staining of several AVT
      immunoreactive nerve fibres in both the pineal stalk and the gland. In addition,
      polyhedral, neuron-like cell bodies from which two to three processes emerged
      were also AVT-immunoreactive. Thus, our investigation shows the presence of
      AVP/AVT-immunoreactive cellular structures in the bovine pineal gland. Our data
      further show the presence of mRNAs encoding both AVT and AVP. We therefore
      suggest that AVT mRNA is translated into an AVT-like peptide in the bovine
      pineal.

PMID- 9931369
TI  - Sheep 5HT2A receptors: partial cloning of the coding sequence and mRNA
      localization by in situ hybridization in the ewe hypothalamus.
AB  - Serotonin and serotonin receptors of class II (5HT2-R) are thought to be involved
      in the neural mechanisms which regulate the LH release associated with
      photoperiodic changes in sheep. A specific premammillary hypothalamic area
      displaying a significant binding of 3H-ketanserin, a potent 5HT2-R antagonist,
      was previously identified. The aim of the present study was to ascertain by in
      situ hybridization (ISH) that 5HT2-R mRNA-containing cells were also present in
      this specific hypothalamic area. Total RNA was prepared from sheep pars
      tuberalis/median eminence, and a cDNA fragment of 546 bp was amplified by reverse
      transcriptase polymerase chain reaction (RT-PCR) using degenerated primers
      deduced from the human and rat 5HT2A-R sequences. After cloning and sequencing,
      the sheep nucleotide sequence had the highest homology (85.1-92.3%) with the
      other known mammalian 5HT2-R or 5HT2A-R sequences. Homology with other 5HT-R
      subtypes or other monoamine receptors was much lower, 60% at maximum. After ISH
      using sense and antisense 35S-riboprobes, specific labelling was found in
      different parts of the hypothalamus, especially in the mammillary bodies where
      the binding was higher. Within the hypothalamus, the density of labelled cells,
      mainly neurons, varied considerably. It was maximal in the mammillary bodies and
      also in a restricted ventral region of the premammillary hypothalamus located
      from about 500/700 micrometer to 1200/1400 micrometer in front of the mammillary
      recess, where 3H-ketanserin binding was previously reported. IN CONCLUSION: (1)
      the structural study of the sequence indicated that the new cloned cDNA
      corresponds to the sheep 5HT2-R class and, probably, to the 5HT2A-R subtype and
      (2) the ISH studies revealed that a restricted area of the premammillary
      hypothalamus shows a large number of 5HT2-R mRNA-containing neurons.

PMID- 9931370
TI  - Motor innervation by enteric nerve fibers containing both nitric oxide synthase
      and galanin immunoreactivities in the striated muscle of the rat esophagus.
AB  - The relationship between nitric oxide synthase (NOS)- and galanin-immunoreactive
      nerve terminals and the origin of NOS-immunoreactive nerve terminals on the motor
      endplates in the striated muscles of the rat esophagus was investigated. Double
      immunohistochemical staining revealed a dual innervation of motor endplates by
      calcitonin gene-related peptide (CGRP)-immunoreactive axons and by axons that
      were immunoreactive for both NOS and galanin. On average, 91% of NOS terminals
      were galanin immunoreactive. NOS-immunoreactive fibers were revealed at 67% of
      endplates, identified by the presence of CGRP terminals. The left vagus and
      superior laryngeal nerve were cut and 15 days allowed for terminals to
      degenerate. This caused a significant loss of CGRP fibers, but did not affect the
      density of innervation of the striated muscle by NOS-immunoreactive fibers. Thus
      the NOS/galanin fibers are deduced to originate from ganglia in the esophageal
      wall. This is supported by our observation of numerous NOS-immunoreactive nerve
      cell bodies in the myenteric ganglia of the esophagus, 74% of which were galanin
      immunoreactive. There were no CGRP-immunoreactive nerve cell bodies in the wall
      of the esophagus.

PMID- 9931371
TI  - Intimate relationship between interstitial cells of cajal and enteric nerves in
      the guinea-pig small intestine.
AB  - Recent studies have suggested that enteric inhibitory neurotransmission is
      mediated via interstitial cells of Cajal in some gastrointestinal tissues. This
      study describes the physical relationships between enteric neurons and
      interstitial cells of Cajal in the deep muscular plexus (IC-DMP) of the guinea
      pig small intestine. c-Kit and vimentin were colocalized in the cell bodies and
      fine cellular processes of interstitial cells of the deep muscular plexus. Anti
      vimentin antibodies were subsequently used to examine the relationships of
      interstitial cells with inhibitory motor neurons (as identified by nitric oxide
      synthase-like immunoreactivity) and excitatory motor neurons (using substance P
      like immunoreactivity). Neurons with nitric oxide synthase- and substance P-like
      immunoreactivities were closely associated with the cell bodies of interstitial
      cells and ramified along their processes for distances greater than 300
      micrometer. With transmission electron microscopy, we noted close relationships
      between interstitial cells and the nitric oxide synthase- and substance P-like
      immunoreactive axonal varicosities. Varicosities of nitric oxide synthase and
      substance P neurons were found as close as 20 and 25 nm from interstitial cells,
      respectively. Specialized junctions with increased electron density of pre- and
      postsynaptic membranes were observed at close contact points between nitric oxide
      synthase- and substance P-like immunoreactive neurons and interstitial cells.
      Close structural relationships (approximately 25 nm) were also occasionally
      observed between either nitric oxide synthase- and substance P-like
      immunoreactive varicosities and smooth muscle cells of the outer circular muscle
      layer. The data suggest that interstitial cells in the deep muscle plexus are
      heavily innervated by excitatory and inhibitory enteric motor neurons. Thus,
      these interstitial cells may provide an important, but probably not exclusive,
      pathway for nerve-muscle communication in the small intestine.

PMID- 9931372
TI  - Immunolocalization of latent transforming growth factor-beta binding protein-1
      (LTBP1) during mouse development: possible roles in epithelial and mesenchymal
      cytodifferentiation.
AB  - Latent transforming growth factor-beta binding protein-1 (LTBP1) is a member of
      the fibrillin family; it is a glycoprotein of more than 190 kDa that is
      characterized by its possession of 16-18 epidermal growth factor-like motifs and
      8 cysteine residues. The secretion of transforming growth factor-beta involves
      its release from cells in a large latent complex containing LTBP1, a latency
      associated peptide, and the mature region of the growth factor. Using a
      polyclonal antibody specific for LTBP1 (Ab39), we examined the
      immunohistochemical localization of this molecule during mouse embryogenesis
      between 8.5 and 13.5 embryonic days. An extracellular fibrillar structure
      containing LTBP1 was found in both the basement membrane of epithelia and
      mesenchymal tissue in which extensive tissue remodeling is carried out.
      Immunoelectron microscopy revealed Ab39 immunoreactivity on a 5- to 10-nm
      microfibrillar component of these basement membranes as well as in mesenchymal
      tissue. These results suggest that LTBP1 is one of the extracellular
      microfibrillar components of the basement membrane and of mesenchymal tissue, and
      that it may play an important role in the regulation of developmental phenomena
      involved in epithelial-mesenchymal interaction and epithelial differentiation,
      processes in which transforming growth factor-beta is required for the control of
      cellular differentiation.

PMID- 9931373
TI  - Cytochemical localization of GalNAc and GalNAcbeta1,4Galbeta1,4 disaccharide in
      mouse zona pellucida.
AB  - Carbohydrate residues contained in the zona pellucida play a key role in the
      process of sperm-egg interaction. In vitro fertilization experiments have shown
      that a specific monoclonal antibody against GalNAcbeta1,4Galbeta1,4 disaccharide
      inhibits fertilization in mice. In the present study, the ultrastructural
      cytochemical localization of GalNAc residues and the GalNAcbeta1,4Galbeta1,4
      disaccharide was carried out in ovarian and postovulatory oocytes by using lectin
      gold cytochemistry and immunocytochemistry. Plant lectins SBA and DBA showed an
      affinity for the entire zona pellucida matrix of ovarian oocytes throughout the
      follicular maturation; however, immunoreactivity for GalNAcbeta1,4Galbeta1,4
      disaccharide was not detected in ovarian oocytes at the earliest stages of
      follicular development but was found to be associated with the inner region of
      the zona matrix at the trilaminar primary follicle stage. The Golgi apparatus,
      vesicular aggregates, and cortical granules of the oocyte were intensely labeled
      by SBA and DBA throughout follicular development. Immunoreactivity to
      GalNAcbeta1,4Galbeta1,4 disaccharide was first observed in the Golgi apparatus
      and vesicular aggregates in trilaminar primary follicles. No immunoreactivity was
      observed in the cortical granules. In postovulatory oocytes, results were similar
      to those observed in ovarian oocytes. Our results thus suggest that (1)
      GalNAcbeta1,4Galbeta1,4 disaccharide residues are present only in the inner
      region of the zona pellucida and, therefore, might be involved in sperm
      penetration through the zona pellucida, (2) the inner and outer regions of the
      zona pellucida contain different oligosaccharide chains, (3) the vesicular
      aggregates detected in the oocyte could represent an intermediate step in the
      secretory pathway of zona pellucida glycoproteins and might be involved in the
      formation of cortical granules.

PMID- 9931374
TI  - Immunohistochemical localization of a water channel, aquaporin 7 (AQP7), in the
      rat testis.
AB  - Cell volume reduction is one of the most distinct morphological changes during
      spermiogenesis and may be largely attributable to water efflux from the cell. A
      strong candidate for a water efflux route, aquaporin 7 (AQP7), which is a water
      channel, was studied immunohistochemically in the rat testis. Immunoreactivity
      was restricted within the elongated spermatids, testicular spermatozoa, and
      residual bodies remaining in the seminiferous epithelium. Weak but distinct
      immunoreactivity was first observed in the cytoplasmic mass of the spermatid at
      step 8 of spermiogenesis. The Golgi-like apparatus became steadily immunoreactive
      at step 10. The plasma membrane covering the cytoplasmic mass showed strong
      immunoreactivity after step 16. At this step, the middle piece of the tail also
      showed immunoreactivity at the portion protruding into the lumen. The whole head
      and distal tail, where the elongated spermatid had only a limited amount of
      cytoplasm, showed no immunoreactivity throughout spermiogenesis. After
      spermiation, the immunoreactivity of AQP7 remained at the middle piece and in the
      cytoplasmic droplet in the testicular spermatozoon. The present observations
      suggest that AQP7 contributes to the volume reduction of spermatids, since this
      water channel protein is localized on the plasma membrane covering the condensing
      cytoplasmic mass of the elongated spermatid, and since the seminiferous tubule
      fluid is hypertonic.

PMID- 9931375
TI  - Differentiation-dependent expression of gelatinase B/matrix metalloproteinase-9
      in trophoblast cells.
AB  - The purpose of this study was to evaluate the Rcho-1 trophoblast culture system
      as a model for studying trophoblast invasion and to examine stage-specific
      expression of enzyme(s) potentially participating in rat trophoblast giant cell
      invasive behavior. The invasive behavior of the differentiating Rcho-1
      trophoblast cells was demonstrated using Matrigel invasion chambers. Gelatin
      zymography and Western blot analysis of conditioned medium from differentiating
      Rcho-1 trophoblast cell cultures and rat ectoplacental cone outgrowths revealed a
      differentiation-dependent increase in gelatinase B/matrix metalloproteinase (MMP
      9). Nothern blot and reverse transcriptase polymerase chain reaction (RT-PCR)
      analyses of Rcho-1 trophoblast or ectoplacental cone cells also showed increasing
      expression of MMP-9 accompanying cell differentiation. Rcho-1 trophoblast cells
      stably transfected with MMP-9 promoter/luciferase reporter constructs exhibited a
      differentiation-dependent increase in MMP-9 promoter activation. In conclusion,
      trophoblast giant cell differentiation is characterized by transcriptional
      activation of the MMP-9 gene and appearance of the invasive phenotype.

PMID- 9931376
TI  - Paracrine regulation of distinct trophoblast functions in vitro by placental
      macrophages.
AB  - In view of the accumulating evidence for paracrine mechanisms regulating
      trophoblast function, we tested the hypothesis that placental macrophages affect
      trophoblast activity in a paracrine fashion. Trophoblast was isolated from 17
      term placentas (-IP). One aliquot of cells was further immunopurified (+IP) using
      an HLA class I antibody. This increased the proportion of trophoblast (+IP >97%; 
      IP approximately 70%) as identified by rigorous immunocytochemistry. Most
      (approximately 70%) non-trophoblast cells in -IP were macrophages. The cells were
      cultured for 5 days with a daily medium change. In addition, +IP cells from seven
      placentas were cultured with lipopolysaccharide (LPS)-stimulated or -unstimulated
      macrophage-conditioned media. The concentrations of lactate, trophoblast-specific
      hormones, human chorionic gonadotropin-beta (hCG-beta) and human placental
      lactogen (hPL), of several prostanoids and of endothelin-1 and angiotensin II
      were determined in the culture media. The accumulated amounts of substances
      released into the culture media, corrected for the greater proportion of
      trophoblast in +IP cultures, were on average two- to threefold higher (hCG-beta:
      18-fold) in +IP than in -IP, with the exception of endothelin-1,2 (no change),
      angiotensin II (-70%) and 6-keto-prostaglandin-F1alpha (-40%). [3H]leucine
      incorporation into the trichloroacetic acid (TCA)-precipitable pool measured on
      day 5 was twofold higher in +IP than in -IP. Addition of conditioned media
      reverted these changes. The data demonstrate that placental macrophages in
      culture affect trophoblast biosynthetic activity in a paracrine fashion. We
      conclude that macrophages are important regulators of trophoblast activity.

PMID- 9931377
TI  - BDM (2,3-butanedione monoxime), an inhibitor of myosin-actin interaction,
      suppresses myofibrillogenesis in skeletal muscle cells in culture.
AB  - During the initial phase of myofibrillogenesis in developing muscle cells, the
      majority of thin filaments lie parallel to, and exhibit correct polarity and
      spatial position with thick filaments, as in mature myofibrils. Since myosin is
      known to function as an accelerator of actin polymerization in vitro, it has been
      postulated that myosin-actin interaction is important in the initial phase of
      myofibrillogenesis. To clarify further the role of actin-myosin interaction in
      myofibril formation during development, BDM (2, 3-butanedione 2-monoxime), an
      inhibitor of myosin ATPase, was applied to primary cultures of skeletal muscle to
      inhibit myosin activity during myofibrillogenesis, and myofibril formation was
      examined. When 10 mM BDM was added to the myotubes just after fusion and the
      cultures were maintained for a further 4 days, cross-striated myofibrils were
      scarcely observed by fluorescence microscopy when examined by staining with
      antibodies to actin, myosin, troponin and alpha-actinin, whereas in the control
      myotubes not exposed to BDM, typical sarcomeric structures were detected.
      Electron microscopy revealed a disorganized arrangement of myofilaments and
      incomplete sarcomeric structures in the BDM-treated myotubes. Thus, formation of
      cross-striated myofibrils was remarkably suppressed in the BDM-treated myotubes.
      When the myotubes cultured in BDM-containing media were transferred to control
      media, sarcomeric structures were formed in 2-3 days, suggesting that the
      inhibitory effect of BDM on myotubes is reversible. These results suggest that
      actin-myosin interaction plays a critical role in the early process of
      myofibrillogenesis.

PMID- 9931378
TI  - Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat
      lung in hyperoxic pulmonary hypertension.
AB  - Breathing air with a high oxygen tension induces an inflammatory response and
      injures the microvessels of the lung. The resulting development of smooth muscle
      cells in these segments contributes to changes in vasoreactivity and increased
      pulmonary artery pressure. This in vivo study determines the temporal and spatial
      expression of endogenous endothelial nitric oxide synthase (NOS III) and
      inducible NOS (NOS II), important enzymes regulating vasoreactivity and
      inflammation, in the adult rat lung during the development of experimental
      pulmonary hypertension induced by oxidant injury. We analyzed the cellular
      distribution of these NOS isoforms, using specific antibodies, and assessed
      enzyme activity at baseline and after 1-28 days of hyperoxia (FIO2 0.87). The
      number of NOS III-immuno-positive endothelial cells increased early in hyperoxia
      and then remained high. By day 28, the relative number of these cells had
      increased from 40% in proximal vessels and 13-16% in distal alveolar vessels of
      the normal lung to 73-86% and 40-59%, respectively, in hyperoxia. Pulmonary
      alveolar macrophages (PAMs), normally few in number and only weakly
      immunopositive for NOS II or III in the normal lung, increased in number in
      hyperoxia and were strongly immunopositive for each isoform. These morphological
      data were supported by a temporal increase in total and calcium-independent NOS
      activity. Thus NOS expression and activity significantly increased in hyperoxia
      as pulmonary hypertension developed, and NOS III expression increased selectively
      in vascular endothelial cells, while both NOS isoforms were expressed by the PAM
      population. We conclude that this increase in expression of a potent vasodilator,
      an antiproliferative agent for smooth muscle cells, and an antioxidant molecule
      represents an adaptive response to protect the lung from oxidant-induced vascular
      and epithelial injury.

PMID- 9931379
TI  - Immunohistochemical evidence for the presence, localization and partial
      coexistence of insulin, insulin-like growth factor I and relaxin in the
      protochordate Ciona intestinalis.
AB  - The occurrence and coexistence of peptides of the insulin-like growth factor
      (IGF)/insulin superfamily were investigated in the ovary and gastro-intestinal
      tract of the protochordate Ciona intestinalis. Antisera specific for mammalian
      IGF-I, insulin and relaxin were used in a double-immunofluorescence method on
      paraffin sections and with an immunogold technique on consecutive semi-thin
      sections. IGF-I and relaxin immunoreactions but no insulin immunoreactions
      occurred in the ovary and were confined to medium-sized and mature follicle
      cells. Two subpopulations of reacting follicular cells were present: those
      containing only IGF-I immunoreactivity (5%) and those containing IGF-I and
      relaxin immunoreactivities (95%). In the gastro-intestinal tract, IGF-I and
      insulin immunoreactions coexisted, whereas no relaxin immunoreactions were
      obtained. Gel chromatography and radioimmunoassay in Ciona ovary revealed IGF-I
      immunoreactivity in two peaks with apparent molecular masses of approximately 16
      kDa and 3 kDa. The present results indicate that (1) the same IGF-I-related
      peptide probably occurs in gastro-intestinal tract and ovary, (2) three different
      members of the insulin/IGF family of peptides are probably present in
      protochordates, (3) different types of coexistence of these peptides seem to
      exist in protochordates, i.e. an IGF-I-related peptide and an insulin-related
      peptide in the digestive tract and, as shown previously, in central nervous
      system, and the IGF-I-related peptide and relaxin in the ovary, (4) an IGF-I
      related peptide and relaxin may be involved in oocyte maturation in the
      protochordate ovary.

PMID- 9931380
TI  - Pigment-dispersing hormone-like immunoreactive neurons in the central nervous
      system of the gastropods, Helix pomatia and Lymnaea stagnalis.
AB  - By using an antiserum raised against a crustacean beta-pigment-dispersing hormone
      (PDH), the distribution and chemical neuroanatomy of PDH-like immunoreactive
      neurons was investigated in the central nervous system of the gastropod snails,
      Helix pomatia and Lymnaea stagnalis. The number of immunoreactive cells in the
      Helix central nervous system was found to be large (700-900), whereas in Lymnaea,
      only a limited number (50-60) of neurons showed immunoreactivity. The
      immunostained neurons in Helix were characterized by rich arborizations in all
      central ganglia and revealed massive innervation of all peripheral nerves and the
      neural (connective tissue) sheath around the ganglia and peripheral nerve trunks.
      A small number of Helix nerve cell bodies in the viscero-parietal ganglion
      complex were also found to be innervated by PDH-like immunoreactive processes.
      Hence, a complex central and peripheral regulatory role, including neurohormonal
      actions, is suggested for a PDH-like substance in Helix, whereas the sites of
      action may be more limited in Lymnaea.

PMID- 9931382
TI  - Microvillar orientation in the photoreceptors of the ant Cataglyphis bicolor.
AB  - Polarization sensitivity in arthropod photoreceptors is crucially dependent on
      the arrangement of the microvilli within the rhabdom. Here, we present an
      electron-microscopical study in which the degree of microvillar alignment and
      changes in the cross-sectional areas of the rhabdoms along their length were
      studied in the compound eye of the desert ant, Cataglyphis bicolor. Serial cross
      sections through the retina were taken and the orientation of the microvilli was
      determined in the photoreceptors of individually identified ommatidia. The
      reconstructions of microvillar alignment were made in the three anatomically and
      functionally distinct regions of the Cataglyphis compound eye: the dorsal rim
      area (DRA), the dorsal area (DA), and the ventral area (VA). The following
      morphological findings are consistent with polarization sensitivities measured
      previously by intracellular recordings. (1) The microvilli of the DRA
      photoreceptors are aligned in parallel along the entire length of the cell from
      the distal tip of the rhabdom down to its proximal end, near the basement
      membrane. The microvilli of the retinular cells R1 and R5 are always parallel to
      each other and perfectly perpendicular, with only minor deviation, to the
      microvillar orientation of the remaining receptor cells. (2) In the DA and VA
      regions of the eye, the microvillar tufts of the small receptors R1, R3, R5, R7,
      and R9 change their direction repetitively every 1-4 micrometer for up to 90
      degrees. In contrast, the large receptor cells R2, R4, R6, and R8 maintain their
      microvillar orientation rigidly. (3) In the DRA ommatidia, the cross-sectional
      areas of the rhabdomeres do not change along the length of the rhabdom, but
      substantial changes occur in the DA and VA ommatidia.

PMID- 9931381
TI  - Effect of high-level oxygen exposure on the peroxidase activity and the
      neuromelanin-like pigment content of the nerve net in the earthworm, Lumbricus
      terrestris.
AB  - Histochemical examination of 1-microm tissue sections from the dorsal nerve
      plexus of the earthworm, Lumbricus terrestris, reveals multiple brown
      intraneuronal granules. These granules contain material morphologically and
      histochemically consistent with neuromelanin. When viewed with transmission
      electron microscopy, these were seen as single membrane-enclosed biphasic
      granules with diameters of 370-730 nm. Exposure of L. terrestris to high-level
      environmental oxygen resulted in an increase in the number of neuromelanin-like
      pigment granules within the neurons of the circular muscle layer. As measured by
      ortho-phenylenediamine hydrochloride, the endogenous peroxidase activity of
      extracts from worms incubated in high-level environmental oxygen was 51% more
      than controls. The endogenous peroxidase activity was localized in situ with 3,3
      diaminobenzidine (DAB) and was found to increase in and around the neuromelanin
      like pigment-containing neurons within the circular muscle layer. These studies
      suggest that the nerve net of L. terrestris may serve as a model to study the
      role of neuromelanin production in oxidative stress and its relationship to
      endogenous peroxidases.

PMID- 9931383
TI  - Oxidative stress response induced in rat primary hepatocyte monolayers by
      mechanical removal of adherent cells.
AB  - We show that mechanical separation of adherent rat primary hepatocytes after the
      monolayer-forming stage causes the induction of the oxidative stress genes HO-1
      (haem oxygenase) and MnSOD (manganese superoxide dismutase). The procedures for
      enzymatically breaking up liver tissue structure and isolating hepatocytes do not
      cause HO-1 and MnSOD activation. Only after a 3-h incubation, during which
      hepatocytes form a monolayer on culture dishes, does the hydrodynamic shearing
      away of necrotic cells sticking to the monolayer surface activate these two
      genes. Analysis of this injury-response pathway shows that oxidative stress and
      mitochondrial dysfunction play a role, as activation can be repressed by
      antioxidants and by respiratory inhibitors. Recovery of the cells takes a further
      24-h incubation during which HO-1 and MnSOD expression returns to basal levels.

PMID- 9931384
TI  - Repair of DNA lesion O6-methylguanine in hepatocellular carcinogenesis.
AB  - Evidence from both experimental carcinogenesis and studies in human cirrhotic
      liver suggest that defective repair of the promutagenic DNA base lesion, O6
      methylguanine, is a factor in the multistep process of hepatocellular
      carcinogenesis. Ubiquitous environmental alkylating agents such as N-nitroso
      compounds can produce O6-methylguanine in cellular DNA. Unrepaired, O6
      methylguanine can lead to the formation of G --> A transition mutations, a known
      mechanism of human oncogene activation and tumour suppressor gene inactivation.
      Combined treatment of rodents with an agent producing O6-methylguanine in DNA,
      and an agent promoting cell proliferation, leads to development of hepatic
      nodules and hepatocellular carcinoma (HCC), cell division, hence DNA replication,
      being required for the propagation of tumorigenic mutation(s) in hepatocyte DNA.
      The paramount importance of O6-methylguanine in hepatocellular carcinogenesis is
      indicated by the observation that transgenic mice engineered to have increased
      hepatic levels of repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) are
      significantly less prone to hepatocellular carcinogenesis following alkylating
      agent treatment. Cirrhosis is a universal risk factor for development of human
      HCC, and a condition that is characterized by increased hepatocyte proliferation
      as a result of tissue regeneration. Levels of the human repairing enzyme for O6
      methylguanine were found to be significantly lower in cirrhotic liver than in
      normal tissue. In accord with findings from animal models, this suggested a
      mechanism in which persistence of O6-methylguanine due to defective DNA repair by
      MGMT, together with increased hepatocyte proliferation, might lead to specific
      gene mutation(s) and hepatocellular carcinogenesis. Screening for the presence
      and persistence of O6-methylguanine in human DNA presently involves formidable
      technical difficulty. Indications are that such limitations might be overcome by
      the use of an ultrasensitive method such as immuno-polymerase chain reaction
      (PCR). This approach should allow parallel measurement of DNA adduct and repair
      enzyme in routine liver biopsy samples. It might also enable investigation of O6
      methylguanine in human genes specifically associated with hepatocellular
      carcinogenesis. Given the wide variation in human MGMT levels observed between
      individuals, tissues, and cells, this technology should be adapted to permit the
      ultrasensitive localisation and measurement of adducts and repairing enzyme in
      liver biopsy tissue sections. Ability to ultrasensitively measure O6
      methylguanine, and its repair enzyme, should prove valuable in the risk
      assessment of cirrhotic patients for developing hepatocellular carcinoma.

PMID- 9931385
TI  - Hepatitis B x antigen and p53 in the development of hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) is one of the major etiological agents responsible for
      the appearance of chronic liver diseases, including hepatocellular carcinoma
      (HCC). There is increasing evidence that the HBV excoded x antigen (HBxAg) is
      involved in one or more steps that contribute to multistep hepatocarcinogenesis.
      Recent work has now defined one of these steps as the physical binding and
      functional inactivation of the tumor suppressor protein, p53, by HBxAg. The
      centrality of p53 to genomic stability, cell cycle arrest, induction of
      apoptosis, and in senescence related pathways, suggests that its disruption by
      HBxAg will result in genomic instability, loss of cell cycle control, a lower
      apoptotic rate, and an extension in the life span of HBV-infected cells. It is
      proposed that HBxAg/p53 complex formation represents one of several steps whereby
      HBV contributes to the development of HCC.

PMID- 9931386
TI  - Cell adhesion molecules in the formation of liver metastasis.
AB  - Metastasis is the most life-threatening event in patients with cancer, with the
      liver being one of the most frequently affected organs. In the development and
      establishment of metastasis, blood-borne cancer cells utilise various cell
      adhesion mechanisms (cell-cell, cell matrix, tumour-endothelial and hepatocyte).
      Thus, cell adhesion molecules have a pivotal role in this process of metastasis
      formation. This article discusses recent progress in the biology of cell adhesion
      molecules in the formation of liver metastasis and the clinical implications of
      the findings.

PMID- 9931387
TI  - Tumor-suppressor genes in pancreatic cancer.

PMID- 9931388
TI  - Stromal degradation by the malignant epithelium in pancreatic cancer and the
      therapeutic potential of proteolytic inhibition.
AB  - off matrix metalloproteinases (MMPs) and the tissue inhibitors of the
      metalloproteinases (TIMPs) are described and reviewed. The role of the MMPs and
      their inhibitors in tumour invasion and metastasis is reviewed and the
      interaction between the extracellular matrix and these enzymes is discussed. The
      expression and activity of the MMPs and TIMPs in pancreatic cancer is reported
      with reference to the literature and the author's own work. The effect of MMP
      inhibitors (MMPIs) in vivo and the use of batimastat and marimastat (both;
      British Biotech Pharmaceuticals, Oxford, UK) in animal experiments are also
      described. Preliminary phase II and III clinical trial data of marimastat in
      advanced pancreatic cancer is reported.

PMID- 9931389
TI  - Mechanisms of reperfusion injury after warm ischemia of the liver.
AB  - The review highlights recent advances in our understanding of basic mechanisms of
      reperfusion injury after warm hepatic ischemia. Kupffer cells play a central role
      as the initial cytotoxic cell type and as a source of many proinflammatory
      mediators. Subsequently, neutrophils are activated and recruited into the liver.
      Factors and conditions are outlined that determine whether neutrophils undergo
      apoptosis without causing damage or migrate out of the sinusoids and attack
      parenchymal cells. In addition to the inevitable inflammatory response during
      reperfusion, microcirculatory perfusion failure, due to an imbalance between the
      actions of vasodilators and vasoconstrictors, also has a serious impact on
      reperfusion injury. A better understanding of the basic pathophysiology will
      reveal potential targets for therapeutic interventions and will show us how to
      avoid risk factors that may aggravate reperfusion injury.

PMID- 9931390
TI  - Apoptosis and the liver: relevance for the hepato-biliary-pancreatic surgeon.
AB  - Cell death by apoptosis is thought to be involved in various pathophysiological
      situations involving the liver. Indeed, an understanding of apoptosis is becoming
      increasingly helpful for understanding disease and for patients' care. In this
      article, we review current scientific and clinical concepts of apoptosis,
      including death factors such as Fas ligand and tumor necrosis factor, apoptotic
      signal transduction mechanisms, and the role of intracellular proteinases called
      caspases. We also discuss apoptosis in the liver, as related to
      ischemia/reperfusion injury, cholestasis, and cancer, circumstances which
      physicians often face in the field of the liver surgery.

PMID- 9931391
TI  - Isolated caudate lobectomy by anterior approach for hepatocellular carcinoma
      originating in the paracaval portion of the caudate lobe.
AB  - We aimed to assess isolated caudate lobectomy by the anterior approach for the
      treatment of large hepatocellular carcinomas originating in the paracaval portion
      of the caudate lobe. The surgical procedures consisted of ligation and dissection
      of the caudate branch of the portal vein and short hepatic veins from the right
      side of the hepatic hilum; liver resection cranially from the right side of the
      process portion; ligation and dissection of the short hepatic veins from the left
      side; hepatic resection between the lateral segment and Spiegel lobe; and,
      finally, dissection of the liver at the right of the Cantlie line, reaching the
      tumor in the paracaval portion of the caudate lobe. The important point in this
      procedure was the appropriate management of the short hepatic veins, the branches
      of the hepatic vein, and the glisson's vessels of the paracaval portion. The
      operative times for the three patients reported here were 430, 355, and 575 min,
      with blood loss of 1100, 1180, and 2000 ml, respectively. The duration of the
      operation was short and blood loss was minimal; severe complications were not
      observed. Complete recovery of liver function after this surgery tended to be
      slow. Early recurrence was observed during long-term follow-up. This procedure is
      considered to be a safe method, with optimal surgical vision for caudate lobe
      tumors of a relatively large size. However, adjuvant therapy to prevent
      recurrence is required.

PMID- 9931392
TI  - Effect of a specific synthetic inhibitor of neutrophil elastase (ONO-5046) on the
      course of acute hemorrhagic pancreatitis in dogs.
AB  - In acute pancreatitis, particularly in severe cases, polymorphonuclear neutrophil
      (PMN) elastase induces tissue damage in remote organs such as the lung, as well
      in the pancreas itself. Therefore, we examined the therapeutic effect of a
      specific synthetic inhibitor of PMN elastase (ONO-5046: Ono Pharmaceuticals,
      Osaka, Japan) on the lung, liver, and kidney, as well as pancreas, in severe
      hemorrhagic pancreatitis in dogs. Acute hemorrhagic pancreatitis was induced by
      the injection of a mixture of autologous bile and porcine trypsin into the main
      pancreatic duct. Lipopolysaccharide (LPS) was administered intravenously as a
      septic challenge. Two animal groups were used. In one group, continuous infusion
      of ONO-5046 was started prior to the injection of LPS (ONO group). In the other
      group (control), saline was infused instead. At the end of the experiment (330
      min after the injection of bile and trypsin), the pancreas revealed severe
      hemorrhagic pancreatitis, and a large amount of bloody ascites had accumulated in
      the peritoneal cavity. The white blood cell count was markedly reduced in
      response to the induction of pancreatitis, and was decreased further by the
      septic attack, irrespective of the administration of ONO-5046, although the count
      increased again in the ONO group. Serum levels of amylase and alpha2
      macroglobulin-trypsin complex increased similarly in both groups following
      administration of bile and trypsin. Serum Ca levels decreased in both groups. At
      the end of the experiment, the wet weight of the lung was slightly higher in the
      control group (without ONO-5046). Microscopically, the pancreas showed severe
      hemorrhage accompanied by extensive interstitial edema in both groups. The lung
      and liver demonstrated mild infiltration of inflammatory cells in the
      interstitium in both groups, although the inflammatory change in the liver was
      slightly milder in the ONO group. These findings indicate that severe hemorrhagic
      pancreatitis cannot be alleviated by the administration of a specific inhibitor
      of PMN elastase alone, although this may lessen damage to remote organs such as
      the liver and lung. The white blood cell count decreased markedly after the
      induction of acute pancreatitis, and much more after a septic challenge. This
      seems to be closely related to the accumulation of bloody ascites in the
      peritoneal cavity.

PMID- 9931393
TI  - Results of surgical treatments and prognostic factors for hepatic hilar bile duct
      cancer.
AB  - Results of surgical treatments for 57 patients who underwent resection for
      hepatic hilar bile duct cancer between 1984 and 1997 were studied. Bile duct
      resection was performed in eight patients, and combined resection of bile duct
      and liver was performed in 49 patients, of whom vascular reconstruction was added
      in 15 patients and pancreatoduodenectomy (PD) in six patients. All the operations
      of bile duct resection that were not combined with hepatectomy were non-curative.
      In the patients who underwent combined resection of the bile duct with liver,
      outcomes of the patients with well-differentiated adenocarcinoma were better than
      those with other lower-grade tumors. The factors related to the degree of tumor
      extension, such as serosal invasion, lymph node metastasis, lymphatic vessel
      invasion, perineural invasion, venous vessel invasion, and vascular involvement,
      were other factors which significantly influenced the survival. Curative
      resection yielded significantly better results than non-curative resection. Of
      all these variables, good tumor differentiation and vascular involvement were
      recognized as important prognostic factors by multivariate analysis. Most of the
      postoperative deaths were encountered in patients who underwent additional
      operations to hepatectomy, such as vascular reconstruction or PD. Improvement of
      surgical techniques and perioperative care has yielded better outcomes of
      vascular reconstruction. However, the application of hepatopancreatoduodenectomy
      should be limited due to poor outcomes of widespread bile duct cancer of which
      the histological grade is usually low. Whereas prognosis of bile duct cancer
      involving the hepatic hilus is mainly determined by the biologic characteristics
      of the tumor, surgeons should consider the fact that most patients die of local
      recurrence regardless of the biologic character of the tumor when curative
      resection is not performed.

PMID- 9931394
TI  - The effects of intraportal administration of prostaglandin E1 on liver ischemia
      and hepatectomy in rats.
AB  - The effects of intraportal administration of prostaglandin E1 (PGE1) on portal
      venous flow, hepatic arterial flow, peripheral tissue blood flow, and systemic
      arterial flow before and after 60 min total liver ischemia followed by 70%
      partial hepatectomy in rats were investigated. Total liver ischemia was induced
      by occluding the hepatoduodenal ligament for 60 min. PGE1 at a dose of 0.5
      microg/kg/min was infused intraportally for 15 min before inducing hepatic
      ischemia (preischemic period) and for 60 min after ischemia (postischemic
      reperfusion period) in the treatment group. Normal saline was infused in the
      control group. Seventy percent partial hepatectomy was performed during ischemia.
      Serum biochemical analysis and liver tissue histology were carried out 1, 3, and
      24 h, and 1 and 24 h after reperfusion respectively. One-week survival of the
      PGE1 group was improved to 70% compared to that of the control group of 30%.
      Postischemia reperfusion values of portal and peripheral tissue blood flows in
      the PGE1 group were 6.33 +/- 0.600 ml/min and 27.2 +/- 23.5 (arbitrary), and were
      significantly different from those of the control group of 4.34 +/- 0.400 ml/min
      and 23.5 +/- 5.54 (arbitrary), respectively. There was no significant difference
      in hepatic arterial flow between the two groups. Serum alkaline phosphatase
      decreased significantly in the prostaglandin group. Histological examination
      revealed a significant portal venous congestion in the control group 1 and 24 h
      after reperfusion. The extent of the sinusoidal congestion was also severe in the
      control group 24 h after reperfusion. It was concluded that PGE1 has a protective
      effect against liver damage when the liver was injured by warm ischemia and
      reperfusion followed by partial resection.

PMID- 9931395
TI  - Managing bile duct injury during and after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is now the treatment of choice for gallstones, but
      there has been concern that bile leakage after a laparoscopic cholecystectomy is
      more frequent than after an open cholecystectomy. We have experienced 16 patients
      with bile duct injury after a laparoscopic cholecystectomy. Five patients had a
      circumferential injury to the major bile duct, and we employed a converted open
      technique for biliary reconstruction. The other 11 patients had partial injury to
      the major bile duct, and we performed laparoscopic restoration; all 11 of these
      patients received endoscopic retrograde cholangiography (ERC) on the day after
      the operation and stenting for biliary decompression and drainage. No
      complications were identified and the duration of hospitalization in these
      patients was significantly shorter than in those who had the converted procedure.
      If intraoperative cholangiography is performed routinely, the presence and form
      of bile duct injury can be clearly identified, and the decision to restore the
      site of injury or to convert to the open technique for biliary reconstruction can
      be made immediately.

PMID- 9931396
TI  - Small carcinoma of the pancreas. Factors of prognostic relevance.
AB  - Tumor size seems to be one of the primary prognostic factors that influence
      outcome in pancreatic cancer patients. This finding is reflected in both the
      Japanese and the International Union against Cancer (UICC) staging systems, in
      which T categories have a major influence on stage grouping. To investigate
      whether small tumor size is a prognostic indicator in patients with pancreatic
      carcinoma, we evaluated (in a prospective study) patients with a small pancreatic
      cancer, categorized as T1a (<2 cm) or T1b (<4 cm) tumors according to the UICC
      (1997). PATIENTS AND RESULTS: Of 670 treated patients with pan-creatic
      malignancies, 26 (3.8%) had a small pancreatic tumor (20 T1b; 6 T1a), Twenty-one
      patients were treated by pylorus-preserving duodenopancreatectomy, 4 patients re
      ceived a left pancreatic resection, and 1 patient underwent a total
      pancreatectomy. All procedures included extensive soft tissue clearance. Local
      growth pattern was analyzed according to the Japan Pancreas Society (JPS)
      criteria for pancreatic cancer, i.e., lymph node involvement - N1 (limited to
      group 1 nodes) was found in 6/26 patients. Serosal infiltration - S1 (single
      area) was found in 6/26 and S2 (multiple areas) in 6/26; S3 (infiltration to
      adjacent organs) was found in 1/26. Retroperitoneal infiltration - Rp1 (adjacent
      to the pancreas) was found in 7/26 and Rp2 (not limited to adjacent tissues, but
      no other organs involved) was found in 3/26. Venous involvement (Pv2) was found
      in 1/26. The 5- and 10-year survival rate for the 26 patients was 46%.
      Interestingly, the T1a tumor patients had a significantly lower 5 year survival
      rate than the T1b patients (32% vs 58%; P < 0.05). Of prognostic relevance was
      lymph node metastasis, and retroperitoneal and serosal involvement and these
      patients had a significantly lower 5-year survival rate than those without such
      involvement regardless of tumor size (P < 0. 01). CONCLUSIONS: An overall 5-year
      survival rate of 46% is exceptionally good. Unfortunately, among pancreatic
      cancer patients those with a small carcinoma represent a highly selected group,
      representing less than 5% in our series. Interestingly tumor size is of less
      prognostic relevance than lymph node, retroperitoneal, and serosal involvement.
      Radical resection with extensive soft tissue clearance therefore seems essential
      to achieve such a high survival rate.

PMID- 9931397
TI  - Preduodenal portal vein in the adult.
AB  - Preduodenal portal vein (PDPV) is a rare developmental anomaly. We recently
      encountered this anomaly in a 73-year-old woman who had gastric cancer and
      colonic cancer with liver metastasis. The PDPV was diagnosed preoperatively by
      computed tomography and angiography. To the best of our knowledge, there are only
      19 adult cases reported in the world literature, with this additional case being
      reported here. In infants the anomaly has often been associated with duodenal
      obstruction, but in adults it is often symptomless. We discuss the disease
      process, embryology, diagnosis, association with other anomalies, and surgical
      treatment.

PMID- 9931398
TI  - A long-term surviving patient with cancer of papilla of Vater after local
      resection.
AB  - We report successful local resection for cancer of papilla of Vater in an 86-year
      old woman. She was referred to our hospital because of right hypochondralgia.
      Abdominal ultrasonography and computed tomography showed marked dilatation of the
      common bile duct (CBD). Endoscopic retrograde cholangiography disclosed a small
      shadow defect in the terminal of the dilated CBD. Biopsy of the papilla revealed
      well-to-moderately differentiated adenocarcinoma. Considering her extreme old age
      and keeping in mind her quality of life after the operation, and the finding that
      the tumor was localized within the papilla and highly differentiated, we
      performed local resection. In addition, the intrapancreatic portion of the CBD
      and part of the main pancreatic duct (MPD) were further resected to secure a
      negative margin, confirmed by frozen section. The MPD was reapproximated to the
      duodenal mucosa and a choledocho-duodenostomy was performed for CBD
      reconstruction. Histopathological examination showed the tumor was papillary
      adenocarcinoma, 10 x 15 mm in size; there was no invasion beyond the sphincter of
      Oddi, it had partly infiltrated the CBD, but had not invaded to the pancreas or
      duodenum. The patient's postoperative course was not eventful and she has had
      good quality of life for the past 6 years since the operation, without any
      evidence of recurrence. Although radical pancreaticoduodenectomy is now the
      standard procedure in patients with malignant tumor of the papilla of Vater,
      local resection is a reasonable alternative for high-risk patients with highly
      differentiated, apparently localized carcinomas.

PMID- 9931399
TI  - Idiopathic benign biliary stricture.
AB  - A rare case of idiopathic benign biliary stricture is reported. A 50-year-old man
      with liver dysfunction underwent ultrasonography, which revealed dilation of the
      intrahepatic bile ducts, and endoscopic retrograde cholangiopancreatography,
      which revealed a short, ring-like stenosis at the junction of the left and right
      hepatic ducts. Although a benign stricture was suspected, radiologic tests alone
      were insufficient to make a firm diagnosis. Therefore, a cholecystectomy and
      resection of the extrahepatic biliary tract were performed. Microscopic
      examination of the resected specimen demonstrated no evidence of malignancy. The
      final diagnosis was mild, localized, chronic cholangitis. The patient had not had
      previous biliary tract surgery, choledocholithiasis, nor did he have a congenital
      abnormality of the biliary tract, bile duct carcinoma, or pancreatic disease.
      Since there was no evidence of primary sclerosing cholangitis, the stricture was
      considered to be idiopathic.

PMID- 9931400
TI  - Serous cystadenocarcinoma of the pancreas with liver metastases.
AB  - Serous cystadenocarcinoma of the pancreas is a rare entity. We report a primary
      tumor of the pancreas in a 56-year-old woman that was histologically
      indistinguishable from microcystic adenoma, but which behaved in a malignant
      fashion. Metastatic lesions were found in the liver at the time of the initial
      operation. Nine years after the initial operation, new metastatic liver nodules
      were found, and the histologic characteristics of these lesions were quite
      similar to those of the pancreatic neoplasm. This is a very rare case which may
      support the existence of the entity, serous cystadenocarcinoma of the pancreas.

PMID- 9931401
TI  - Newsletter no. 7, december 1998 asian society of hepato-biliary-pancreatic
      surgery (ASHBPS) 

PMID- 9931402
TI  - Molecular characterisation of plant cDNAs BnMAP4Kalpha1 and BnMAP4Kalpha2
      belonging to the GCK/SPS1 subfamily of MAP kinase kinase kinase kinase.
AB  - Several yeast and mammal MAP kinase modules require, upstream of their MAP kinase
      kinase kinase (MAP3K), a MAP3K kinase (MAP4K). An Arabidopsis thaliana EST clone,
      sharing identity to MAP4Ks from yeast and mammals, has been used to isolate cDNA
      clones from a Brassica napus microspore-derived embryo cDNA library. The
      BnMAP4Kalpha1 and BnMAP4K-alpha2 clones encode putative proteins possessing the
      12 subdomains of the serine/threonine protein kinase catalytic domain. A detailed
      analysis showed that they belong to the GCK/SPS1 subfamily of MAP4K proteins
      which possess an amino terminal catalytic domain and a long carboxy terminal
      tail. A Southern blot analysis suggested that the two proteins are encoded by a
      small multigene family. Expression studies revealed the presence of BnMAP4Kalpha1
      and -alpha2 transcripts in all the tissues examined; however, they are most
      abundant in roots, siliques and flower buds. The expression of BnMAP4Kalpha1 and 
      alpha2 at the three main developmental stages of microspore-derived embryos
      (i.e., globular/heart, torpedo and cotyledonary) was confirmed by northern blot
      and RT-PCR analysis. An expression analysis of the above genes using synchronised
      Arabidopsis thaliana cell suspensions showed that the homologues genes are cell
      cycle regulated.

PMID- 9931403
TI  - Human AIM-1: cDNA cloning and reduced expression during endomitosis in
      megakaryocyte-lineage cells.
AB  - The rat AIM-1 gene encoding an Aurora- and Ipl1-like midbody-associated protein
      serine/threonine kinase has a mitotic regulator function playing a key role in
      the onset of cytokinesis during mitosis. This report presents a cDNA sequence and
      megakaryocytic differentiation-dependent expression profile of the human AIM-1
      gene. The nucleotide sequences of the human AIM-1 were identified from cDNAs of
      three cell lines, including cervical carcinoma HeLa cells, colorectal tumor SW480
      cells, and normal human diploid skin fibroblast NHDF cells, and no mutation was
      found. The expression levels of AIM-1 transcript were markedly reduced during
      differentiation into megakaryocytic cell lineage in human leukemia cells induced
      by 12-o-tetradecanoyl-phorbol-13-acetate (TPA), suggesting that the
      downregulation of AIM-1 contributes to the differentiation by repeated
      duplication of DNA without cytokinesis (endomitosis).

PMID- 9931404
TI  - Genomic organization and evolution of actin genes in the amphioxus Branchiostoma
      belcheri and Branchiostoma floridae.
AB  - We previously described the cDNA cloning and expression patterns of actin genes
      from amphioxus Branchiostoma floridae (Kusakabe, R., Kusakabe, T., Satoh, N.,
      Holland, N.D., Holland, L.Z., 1997. Differential gene expression and
      intracellular mRNA localization of amphioxus actin isoforms throughout
      development: implications for conserved mechanisms of chordate development. Dev.
      Genes Evol. 207, 203-215). In the present paper, we report the characterization
      of cDNA clones for actin genes from a closely related species, Branchiostoma
      belcheri, and the exon-intron organization of B. floridae actin genes. Each of
      these two amphioxus species has two types of actin genes, muscle and cytoplasmic.
      The coding and non-coding regions of each type are well-conserved between the two
      species. A comparison of nucleotide sequences of muscle actin genes between the
      two species suggests that a gene conversion may have occurred between two B.
      floridae muscle actin genes BfMA1 and BfMA2. From the conserved positions of
      introns between actin genes of amphioxus and those of other deuterostomes, the
      evolution of deuterostome actin genes can be inferred. Thus, the presence of an
      intron at codon 328/329 in vertebrate muscle and cytoplasmic actin genes but not
      in any known actin gene in other deuterostomes suggests that a gene conversion
      may have occurred between muscle and cytoplasmic actin genes during the early
      evolution of the vertebrates after separation from other deuterostomes. A
      Southern blot analysis of genomic DNA revealed that the amphioxus genome contains
      multiple muscle and cytoplasmic actin genes. Some of these actin genes seem to
      have arisen from recent duplication and gene conversion. Our findings suggest
      that the multiple genes encoding muscle and cytoplasmic actin isoforms arose
      independently in each of the three chordate lineages, and gene duplications and
      gene conversions established the extant actin multigene family during the
      evolution of chordates.

PMID- 9931405
TI  - Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and
      fecal steroid excretion in regard to their hypolipidemic action in hamsters.
AB  - To examine the impact on bile acid metabolism and fecal steroid excretion as a
      mechanism involved in the lipid-lowering action of beta-cyclodextrin and
      resistant starch in comparison to cholestyramine, male golden Syrian hamsters
      were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1%
      cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine
      significantly lowered plasma total cholesterol and triacylglycerol concentrations
      compared to control. Distinct changes in the bile acid profile of gallbladder
      bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While
      cholestyramine significantly reduced chenodeoxycholate independently of its
      taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased
      especially the percentage of taurochenodeoxycholate by -75% and -44%,
      respectively. As a result, the cholate:chenodeoxycholate ratio was significantly
      increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while
      resistant starch revealed no effect on this ratio. beta-Cyclodextrin and
      resistant starch, not cholestyramine, significantly increased the glycine:taurine
      conjugation ratio demonstrating the predominance of glycine conjugated bile
      acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta
      cyclodextrin and 19-times with 1% cholestyramine compared to control. beta
      Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral
      sterol excretion, demonstrating the sterol binding capacity of these two
      compounds. Resistant starch had only a modest effect on fecal bile acid excretion
      (80% increase) and no effect on excretion of neutral sterols, suggesting a weak
      interaction with intestinal steroid absorption. These data demonstrate the lipid
      lowering potential of beta-cyclodextrin and resistant starch. An impaired
      reabsorption of circulating bile acids and intestinal cholesterol absorption
      leading to an increase in fecal bile acid and neutral sterol excretion is most
      likely the primary mechanism responsible for the lipid-lowering action of beta
      cyclodextrin. In contrast, other mechanisms involving the alterations in the
      biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL
      production, appear to be involved in the hypolipidemic effect of resistant
      starch.

PMID- 9931406
TI  - Protein tyrosine phosphatases: counting the trees in the forest.
AB  - The recent identification of many different protein tyrosine phosphatases (PTPs)
      has led to the recognition that these enzymes match protein tyrosine kinases
      (PTKs) in importance for intracellular signalling. The total number of PTPs
      encoded by the mammalian genome has been estimated at between 500 and approx.
      2000. These estimates are imprecise due to the large number of sequence database
      entries that represent different splice forms, or duplicates of the same PTP
      sequence. A careful analysis of these entries, grouped by identical catalytic
      domain shows that no more than 48 full-length PTP sequences are currently known,
      and that their total number in the human genome may not exceed 100. An alignment
      of all catalytic domains also suggests that during evolution intragenic catalytic
      domain duplication, as seen in most membrane-bound PTPs, preceded gene
      duplication.

PMID- 9931407
TI  - Glypican 3 and glypican 4 are juxtaposed in Xq26.1.
AB  - Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) gene
      cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS; ). The next
      centromeric gene detected is another glypican, glypican 4 (GPC4), with its 5' end
      120763bp downstream of the 3' terminus of GPC3. One recovered GPC4 cDNA with an
      open reading frame of 1668nt encodes a putative protein containing three heparan
      sulfate glycosylation signals and the 14 signature cysteines of the glypican
      family. This protein is 94.3% identical to mouse GPC4 and 26% identical to human
      GPC3. In contrast to GPC3, which produces a single transcript of 2.3kb and is
      stringently restricted in expression to predominantly mesoderm-derived tissues,
      Northern analyses show that GPC4 produces two transcripts, 3.4 and 4.6kb, which
      are very widely expressed (though at a much higher level in fetal lung and
      kidney). Interestingly, of 20 SGBS patients who showed deletions in GPC3, one was
      also deleted for part of GPC4. Thus, GPC4 is not required for human viability,
      even in the absence of GPC3. This patient shows a complex phenotype, including
      the unusual feature of hydrocephalus; but because an uncle with SGBS is less
      affected, it remains unclear whether the GPC4 deletion itself contributes to the
      phenotype.

PMID- 9931408
TI  - Studies on cycloheximide-sensitive and cycloheximide-resistant ribosomes in the
      yeast Candida maltosa.
AB  - Cycloheximide sensitivity or resistance in yeast is under the control of genes
      encoding different forms of ribosomal protein L41. In our previous studies, we
      have shown by isolating L41-Q1a, L41-P1a and their respective allelic genes, L41
      Q1b and L41-P1b, from the partial diploid genome of C. maltosa, that this
      species, which is inducibly resistant to CYH, has both types of the L41 genes and
      that the expression of at least one of the L41-Q genes is induced by CYH, whereas
      L41-P genes are constitutively expressed. Here, we have identified another L41
      (L41-Q2a), its allelic gene (L41-Q2b) and a third gene (L41-Q3) from the genome
      of C. maltosa. By gene disruption experiments, we now show that L41-Q1a and L41
      Q1b are not responsible for the resistance to CYH and that the DeltaL41-Ps
      strain, which has only functional L41-Q genes, shows constitutive resistance to
      CYH, but grows more slowly than the DeltaL41-Qs strain, which has only functional
      L41-P genes, in the absence of CYH. Our results also show that in vitro,
      ribosomes containing L41-Q-type are less active in translation than those
      containing L41-P-type, although only the former ribosomes are active in the
      presence of CYH. These data suggest that ribosomes containing L41-Q-type are less
      active under normal growth conditions, but that this activity is not affected in
      the presence of CYH. We discuss the possible multi-step evolutionary event(s) by
      which C. maltosa has acquired the property of inducible resistance to CYH.

PMID- 9931409
TI  - Cloning, characterisation and expression of the alpha-tubulin genes of the leech,
      Hirudo medicinalis.
AB  - We have isolated two alpha-tubulin cDNAs from the leech, Hirudo medicinalis. Both
      encode putative proteins of 451 amino-acids which differ from each other at only
      two positions. Southern blotting suggests that there are only two alpha-tubulin
      genes in the leech. The genes contain two introns and, because of the extremely
      high homology of the nucleotide sequence from the second intron to the end of the
      genes, we have inferred that a gene conversion event about 9.5 million years ago
      has homogenised the Hirudo alpha-tubulin sequences. Using in situ hybridisation
      to tissue sections, we have shown that the two genes are probably expressed in
      all neurons of the leech ganglia and that their spatial distribution remains
      unchanged during neuronal regeneration. The deduced amino-acid sequences of the
      leech alpha-tubulins show that they have greatest similarity to those from a
      platyhelminth, echiuran and mollusc with rather less to arthropod alpha-tubulins.
      The protein sequences of the leech alpha-tubulins have been compared with
      representatives of those from across all phyla to determine if any specific
      feature labels certain isotypes of tubulin for neuronal expression.

PMID- 9931410
TI  - A sensitive chemiluminescence method to measure the lipoxygenase catalyzed
      oxygenation of complex substrates.
AB  - Oxidative modification of low-density lipoprotein (LDL) has been implicated as a
      patho-physiological process in early atherogenesis and 15-lipoxygenases (15-LOX)
      may be involved. While studying the in vitro kinetics of the 15-LOX/LDL
      interaction, we found that the conventional spectrophotometric assays failed in
      the range of substrate saturation owing to the high optical density of
      concentrated LDL solutions. Therefore, we developed a much more sensitive assay
      system which was based on peroxide induced isoluminol enhanced chemiluminescence.
      With this method reliable kinetic data were obtained at LDL concentrations of up
      to 1 mg/ml. To validate this luminometric method the kinetic parameters of 15-LOX
      catalyzed oxygenation of linoleic acid (Km=3.7 microM, kcat=17 s-1) were
      determined and we observed a good agreement with previously published data
      obtained with a spectrophotometric assay. Moreover, we found that the kinetic
      constants of 15-LOX catalyzed LDL oxidation (Km=0.64 microM, kcat=0.15 s-1) are
      quite different from those of free fatty acid oxygenation and that the
      cholesterol esters are preferentially oxidized during 15-LOX/LDL interaction.
      Vitamin E depletion does not reduce the rate of LDL oxidation and analysis of the
      structure of the oxygenation products suggests that the majority of the products
      were formed via direct LOX catalyzed oxidation of LDL ester lipids. The
      luminometric method described here is not restricted to the measurement of LOX
      catalyzed LDL oxidation, but may also be used to determine kinetic constants for
      the oxidation of other complex substrates such as biomembranes or liposomes.

PMID- 9931411
TI  - Structural properties of Friedreich's ataxia d(GAA) repeats.
AB  - The expansion of trinucleotide repeat sequences is the underlying cause of a
      growing number of inherited human disorders. To provide correlations between DNA
      structure and mechanisms of trinucleotide repeat expansion, we investigated
      potential secondary structures formed from the complementary strands of
      d(GAA.TTC)n, a sequence whose expansion is associated with Friedreich's ataxia.
      In 50 mM NaCl, pH 7.5, d(GAA)15 exhibited a cooperative and reversible decrease
      in large circular dichroism bands at 248 and 272-274 nm over the temperature
      range of 5-50 degrees C, providing evidence for a base-paired structure at
      reduced temperatures. Ultraviolet absorbance melting profiles indicated that the
      melting temperature (Tm) of d(GAA)15 was 40 degrees C. At 5 degrees C, the
      central portion of d(GAA)15 was hypersensitive to single-strand-specific P1
      nuclease degradation and diethyl pyrocarbonate modification, providing evidence
      for a hairpin conformation. At temperatures between 25 and 35 degrees C in 50 mM
      NaCl, the triplet repeat region of d(GAA)15 was uniformly resistant to
      degradation by P1 nuclease, including the central portion of the sequence. Our
      results indicate that the structure of d(GAA)15 is a hairpin at 5 degrees C,
      unknown but partially base-paired at 37 degrees C, and an approximately random
      coil above 65 degrees C.

PMID- 9931412
TI  - Excision of the tol2 transposable element of the medaka fish, Oryzias latipes, in
      zebrafish, Danio rerio.
AB  - The Tol2 element is a transposable element in Oryzias latipes (the medaka fish)
      found in the tyrosinase gene locus of the tyrosinase-deficient mutant medaka fish
      and has been shown to be excised from the genome during medaka embryogenesis
      (Koga, A., Suzuki, M., Inagaki, H., Bessho, Y., Hori, H., 1996. Transposon
      element in fish. Nature 383, 30). It is, however, not known whether the Tol2
      element is an autonomous element. To determine whether the cloned Tol2 element is
      an autonomous element and whether excision can occur also in the other fish
      species, the plasmid DNA harboring the Tol2 element was injected to fertilized
      eggs of zebrafish, Danio rerio, and the total DNA extracted from the embryos 9
      10h after the injection was analyzed by PCR. When a plasmid with the full-length
      Tol2 element was used for the microinjection, in 39 out of 43 injected embryos,
      we found generation of short PCR products indicative of the loss of the Tol2
      element from the injected plasmid. Ten of these cases were analyzed at the DNA
      sequence level, and nine of them showed either precise excision of the Tol2
      element (three cases) or nearly precise excision of the element with the addition
      of a few nucleotides of the target duplication (six cases). When a deletion
      version of the Tol2 element that retained the terminal inverted repeats but
      lacked about one-fourth of the open reading frame-coding region was used for the
      microinjection, such short PCR products could not be amplified from any of the
      injected embryos (0 out of 30). Thus, the Tol2 element is capable of excision in
      zebrafish embryos, presumably dependent on a putative transposase encoded by the
      Tol2 element itself. This transient embryonic excision assay using zebrafish
      should be useful to analyze the structure and the function of the transposase and
      cis-elements necessary for excision. Also, this study implies the potential use
      of the Tol2 element in transgenesis and insertional mutagenesis in both zebrafish
      and the medaka fish.

PMID- 9931413
TI  - Triplet repeat variability in the signal peptide sequence of the Xmrk receptor
      tyrosine kinase gene in Xiphophorus fish.
AB  - Trinucleotide repeats in several human genes have been found to undergo
      spontaneous variation in repeat numbers in succeeding generations. Expansion of
      the repeat beyond a certain length causes specific pathological disorders. So
      far, a naturally occurring triplet repeat instability of transcribed sequences
      has been reported only from humans. However, the signal peptide encoding region
      of the receptor tyrosine kinase gene Xmrk from fish of the genus Xiphophorus
      contains a CTG repeat that differs in length even between closely related
      individuals. The consequence of this variability is signal peptides with shorter
      or longer hydrophobic core regions reaching, in some individuals, the critical
      maximum length for functional protein export or even exceeding it. In one stock,
      animals that are homozygous for such an allele were extremely rare, indicating
      that the triplet repeat length variability of the Xmrk gene of Xiphophorus may
      indeed have an influence on the function of the gene product and, under certain
      conditions, may affect the fitness of the individual.

PMID- 9931414
TI  - Insertion of a foreign gene into the beta-casein locus by Cre-mediated site
      specific recombination.
AB  - The expression of foreign genes in transgenic animals is generally unpredictable
      as transgenes are integrated at random after pro-nuclear injection into
      fertilized oocytes. In many cases, transgene expression is inhibited by
      neighbouring chromatin structures or by the repeated nature of the multiple
      transgene copies present at the integration site. A strategy involving homologous
      and site-specific recombination has been devised by which single copies of a
      foreign gene can be inserted specifically into the locus of a highly expressed
      gene. As a first step, a loxP recombination target site is introduced by
      homologous recombination into a predetermined gene locus such that the loxP
      sequence is placed next to the promoter region and replaces the translational
      initiation signal. In a subsequent site-specific recombination reaction, a gene
      of interest can be integrated into the pre-existing loxP site. This biphasic
      recombination strategy was used to integrate a luciferase reporter gene into the
      locus of the murine beta-casein gene in embryonic stem cells.

PMID- 9931415
TI  - Dissociable and nondissociable forms of platelet-activating factor
      acetylhydrolase in human plasma LDL: implications for LDL oxidative
      susceptibility.
AB  - Platelet-activating factor acetylhydrolase (PAF-AH) is transported by
      lipoproteins in plasma and is thought to possess both anti-inflammatory and anti
      oxidative activity. It has been reported that PAF-AH is recovered primarily in
      small, dense LDL and HDL following ultracentrifugal separation of lipoproteins.
      In the present studies, we aimed to further define the distribution of PAF-AH
      among lipoprotein fractions and subfractions, and to determine whether these
      distributions are affected by the lipoprotein isolation strategy (FPLC versus
      sequential ultracentrifugation) and LDL particle distribution profile. When
      lipoproteins were isolated by FPLC, the bulk (approximately 85%) of plasma PAF-AH
      activity was recovered within LDL-containing fractions, whereas with
      ultracentrifugation, there was a redistribution to HDL (which contained
      approximately 18% of the activity) and the d>1.21 g/ml fraction (which contained
      approximately 32%). Notably, re-ultracentrifugation of isolated LDL did not
      result in any further movement of PAF-AH to higher densities, suggesting the
      presence of dissociable and nondissociable forms of the enzyme on LDL.
      Differences were noted in the distribution of PAF-AH activity among LDL
      subfractions from subjects exhibiting the pattern A (primarily large, buoyant
      LDL) versus pattern B (primarily small, dense LDL) phenotype. In the latter
      group, there was a relative depletion of PAF-AH activity in subfractions in the
      intermediate to dense range (d=1.039-1.047 g/ml) with a corresponding increase in
      enzyme activity recovered within the d>1.21 g/ml ultracentrifugal fraction. Thus,
      there appears to be a greater proportion of the dissociable form of PAF-AH in
      pattern B subjects. In both populations, most of the nondissociable activity was
      recovered in a minor small, dense LDL subfraction. Based on conjugated dienes as
      a measure of lipid peroxidation, variations in PAF-AH activity appeared to
      contribute to variations in oxidative behavior among ultracentrifugally isolated
      LDL subfractions. The physiologic relevance of PAF-AH dissociability and the
      minor PAF-AH-enriched oxidation-resistant LDL subpopulation remains to be
      determined.

PMID- 9931416
TI  - PCR cloning and expression of the molt-inhibiting hormone gene for the crab
      (Charybdis feriatus).
AB  - A PCR-based genomic DNA walking technique was used to clone the gene for the molt
      inhibiting hormone of the crab, Charybdis feriatus. Several overlapping genomic
      clones were isolated, and the MIH gene for the crab was reconstructed. DNA
      sequence determination of the overlapping clone reveals that the MIH gene spans
      4.3kb and consists of three exons and two introns. Exons 1 and 2 carry a coding
      sequence for the signal peptide, and exons 2 and 3 consist of coding sequence for
      the mature peptide. The exon-intron boundary of the crab MIH gene also follows
      the 'GT-AG rule' for the splice donor and acceptor. The deduced amino acid
      sequence of MIH shows the highest overall similarity to those of the crabs,
      Callinectes sapidus and Carcinus maenas, and the gonad-inhibiting hormone (GIH)
      of the lobster. The putative polyadenylation signal is approximately 1.0kb 3'
      downstream of the termination codon (TGA). Genomic Southern blot analysis
      indicates that few genomic fragments were hybridized to the cDNA probe. The 5'
      flanking region contains a putative promoter with several putative cis elements
      similar to some vertebrate neuropeptide genes. The 530-bp flanking region was
      subcloned separately to two promoterless reporter plasmids carrying either the
      Green Fluorescent Protein gene (GFP) or the Choramphenicol Acetyltransferase gene
      (CAT). The DNA constructs were transfected into insect cells (Sf21) and mouse
      pituitary cells (GH4ZR7), respectively. Green fluorescent protein was detected in
      some of the transfected insect cells, and expression of the CAT was detected in
      cells transfected with DNA constructs containing the crab promoter. By RT-PCR,
      MIH transcripts can be detected in the eyestalk of shrimp in intermolt, early
      premolt, late premolt stages and females that brood their eggs. It can also be
      found in the brain, but not in the ovary, hepatopancreas, muscle and epidermis.
      During early larval development, MIH mRNA can be detected in the pre-hatched and
      the newly hatched larvae. Unlike the adult, the expression of the MIH in the
      larvae is exclusively in the brain.

PMID- 9931417
TI  - Molecular cloning of hSLP-1, a novel human brain-specific member of the band
      7/MEC-2 family similar to Caenorhabditis elegans UNC-24.
AB  - We have isolated and characterized cDNA clones encoding a stomatin-like protein
      (hSLP-1) from a human cerebral cortex cDNA library. The deduced amino acid
      sequence (394 residues) revealed that hSLP-1 is a bipartite protein, containing a
      major stomatin-like part, starting at the N-terminus, and a non-specific lipid
      transfer protein (nsLTP)-domain at the C-terminal end, similar to the
      Caenorhabditis elegans protein UNC-24. Therefore, we conclude that hSLP-1 is the
      human homologue of UNC-24. In addition, the identification of an alternatively
      spliced variant demonstrated that two exon/intron boundaries are conserved in the
      hSLP-1 and unc-24 genes. Northern blot and RNA dot blot analyses showed that the
      2. 2-kb transcript is mainly expressed in the brain, with the highest levels in
      the frontal lobe, cerebral cortex, caudate nucleus, amygdala, temporal lobe,
      putamen, substantia nigra, and hippocampus. This high-level expression of hSLP-1
      in the basal ganglia may also reflect the evolutionary link to UNC-24.

PMID- 9931418
TI  - An A/T-rich cis-element is essential for rat angiotensin II type 1A receptor
      transcription in vascular smooth muscle cells.
AB  - Transcriptional mechanisms regulating the expression of the rat angiotensin II
      type 1A receptor (rAT1AR) gene were investigated in cultured rat vascular smooth
      muscle cells (VSMC). Transcriptional analyses of various 5'-deletion mutants of
      the rAT1AR promoter region, fused upstream from the firefly luciferase gene,
      demonstrated that a 71 base pair (bp) region (-557 to -486 bp, with respect to
      transcription initiation) was necessary for expression of this gene in VSMC.
      Electrophoretic mobility shift assays demonstrated that specific protein-DNA
      complexes were formed with the -516 to -486 bp region of the rAT1AR promoter when
      incubated with VSMC extract. Computer analysis of this region indicated the
      presence of an A/T-rich sequence (i.e., TTTAAAAATAAA) which is similar to a
      myocyte enhancer binding factor 2 (MEF2) cis-regulatory element (i.e.,
      CTTAAAAATAAC). Site-directed mutagenesis of this A/T-rich sequence inhibited
      rAT1AR promoter activity in VSMC, suggesting that this region was necessary for
      expression of this gene in these cells. Immuno-gel shift experiments suggest that
      MEF2 heterodimers may interact with the A/T-rich sequence in the rAT1AR promoter.
      Additionally, it was demonstrated that a transcription factor non-homologous to
      MEF2 can also interact with this A/T-rich site in the rAT1AR promoter. Taken
      together, our results suggest that MEF2 heterodimers, and/or transcription
      factors non-homologous to MEF2, are required to regulate the expression of the
      rAT1AR gene in VSMC.

PMID- 9931419
TI  - Establishment of framework P1 clones for map-based cloning and genome sequencing:
      direct RFLP mapping of large clones.
AB  - Large insert capacity, clone stability and convenient propagation in Escherichia
      coli have made bacterial artificial chromosome and phage P1 vector-based
      libraries the first choice for large-scale sequencing projects, and these
      libraries have also proven useful for chromosome walking. The application of
      these libraries for either purpose is greatly facilitated by the establishment of
      a set of framework clones distributed across the genome. Using a P1-based library
      of Arabidopsis thaliana with genomic inserts of 70-90kb (Liu, Y.-G., Mitsukawa,
      N., Vazquez-Tello, A., Whittier, R.F., 1995. Generation of a high-quality P1
      library of Arabidopsis suitable for chromosome walking. Plant J. 7, 351-358), we
      have now established such a set of framework clones. To date, such clones have
      usually been identified by hybridization to smaller, previously mapped clones
      that detect restriction fragment length polymorphisms (RFLPs). In order to
      establish framework clones more efficiently, we refined protocols for P1 clone
      DNA isolation and RFLP detection in order to employ whole P1 clones directly as
      probes. This strategy enabled a very high rate of RFLP detection, and obviated
      the need to screen the P1 library with smaller RFLP probes. Altogether 95 clones
      were mapped providing a framework into which further clones can be integrated by
      physical overlap.

PMID- 9931420
TI  - Human annexin 31 genetic mapping and origin.
AB  - The cDNA encoding novel human annexin 31 was utilized for chromosomal mapping,
      structural comparison, and phylogenetic analysis to clarify its genetic
      relationship to other annexins. The ANX31 gene locus was mapped by fluorescence
      in situ hybridization to human chromosome 1q21, remote from ten other paralogous
      human annexins on different chromosomes but near the epidermal differentiation
      gene complex, the S100A gene cluster and a breast-cancer translocation region.
      Protein homology testing and characterization of incompletely processed expressed
      sequence tags identified annexin 2 as the closest extant homologue. Maximum
      likelihood analysis confirmed its most recent common ancestor with vertebrate
      annexin 2 and validated its classification, in order of discovery, as annexin 31.
      This subfamily was formed approx. 500-600millionyears ago, subsequent to the gene
      duplication that produced annexin 1. It has diverged relatively rapidly and
      extensively, and specifically in the well-conserved, functionally critical type
      II calcium-binding sites.

PMID- 9931421
TI  - The BCL7 gene family: deletion of BCL7B in Williams syndrome.
AB  - The BCL7A gene, which maps to human chromosome 12q24.13, was cloned through its
      direct involvement with MYC and IGH in a three-way translocation in a Burkitt
      lymphoma cell line. Here, we describe the identification of two related human
      genes, BCL7B and BCL7C, which share 90% identity to the amino-terminal 51 amino
      acids of human BCL7A, as well as 41% identity in the same region to Drosophila
      melanogaster, Caenorhabditis elegans, and Brugia malayi EST sequences. This
      degree of relatedness in the amino-terminal domain suggests we have defined a new
      gene family of unknown function. There was little sequence conservation between
      the family members outside this conserved domain and no identified protein motifs
      could be deduced. Human BCL7B and BCL7C mapped to chromosome 7q11.23, and 16p11,
      respectively. No chromosomal rearrangements affecting BCL7B or BCL7C were
      detected in lymphoid malignancies. BCL7B did, however, map within the region of
      7q11.23 which is commonly deleted in the congenital disorder, Williams syndrome.

PMID- 9931422
TI  - Cloning and characterization of the zebrafish (Danio rerio) aryl hydrocarbon
      receptor.
AB  - The aryl hydrocarbon receptor (AhR) mediates the toxicity of 2,3,7, 8
      tetrachlorodibenzo-p-dioxin (TCDD) and related compounds in vertebrates. To
      further establish zebrafish as a vertebrate model to study the molecular
      mechanism of TCDD toxicity, we have isolated and characterized the cDNA encoding
      the zebrafish aryl hydrocarbon receptor (zfAhR2). Analysis of the deduced protein
      sequence revealed the 1027 amino acid protein is approximately 200 amino acids
      longer than previously isolated receptors. zfAhR2 is homologous to previously
      cloned PAS proteins within the basic helix-loop-helix and PAS domains. The C
      terminal domain of zfAhR2 diverges from the mammalian AhR at position 420, and
      does not contain a Q-rich domain. zfAhR2 mRNA is first detected by Northern blot
      analysis at 24 h post fertilization, and expression increases throughout early
      development. Treatment of zebrafish embryos and zebrafish liver cells with graded
      doses of TCDD results in a dose-dependent increase in zfAhR2 mRNA. The time
      course for zfAhR2 and cytochrome P4501A mRNA induction by TCDD are similar. In
      vitro produced zfAhR2 protein dimerizes with the rainbow trout aryl hydrocarbon
      receptor nuclear translocator (rtARNTb) and binds dioxin response elements
      derived from the rainbow trout CYP1A gene. Finally, transient coexpression of
      zfAhR2 and rtARNTb in COS-7 cells results in a TCDD dose-related increase in
      transcription driven by the rainbow trout CYP1A promoter and enhancer.

PMID- 9931423
TI  - Lipid binding to sterol carrier protein-2 is inhibited by ethanol.
AB  - Sterol carrier protein-2 (SCP-2) is an intracellular lipid carrier protein that
      binds cholesterol, phospholipids, fatty acids and other ligands. It has been
      reported that expression of SCP-2 was increased in brain nerve endings or
      synaptosomes of chronic ethanol-treated mice and it was shown that cholesterol
      homeostasis was altered in brain membranes of chronic ethanol-treated animals.
      Ethanol may interfere with the capacity of SCP-2 to bind cholesterol as well as
      other lipids. This hypothesis was tested using recombinant SCP-2 and fluorescent
      labeled cholesterol, phosphatidylcholine (PC), and stearic acid. The association
      constants (Ka) of the ligand-SCP-2 complex were in the following order: NBD
      cholesterol>NBD-PC>NBD-stearic acid. Ethanol, beginning at a concentration of 25
      mM, significantly reduced the affinity of NBD-cholesterol and NBD-PC for SCP-2.
      Effects of ethanol on the Ka of NBD-stearic acid was significant only at the
      highest concentration that was examined (200 mM). Ethanol significantly increased
      the Bmax of NBD-cholesterol for SCP-2 but did not have a significant effect on
      the Bmax of NBD-PC. Similar results were found for effects of ethanol on the Kas
      and Bmaxs using pyrene-labeled cholesterol and PC. In conclusion, ethanol
      beginning at a physiological concentration of 25 mM inhibited binding of
      cholesterol and PC to SCP-2. However, effects of ethanol on lipid binding to SCP
      2 were dependent on the type of lipid. Ethanol in vivo may interfere with lipid
      binding to SCP-2 and disrupt lipid trafficking within cells.

PMID- 9931424
TI  - The PY-motif of Bul1 protein is essential for growth of Saccharomyces cerevisiae
      under various stress conditions.
AB  - The previously identified BUL1 gene was found to encode a protein bound to Rsp5
      ubiquitin ligase in budding yeast. We have identified the BUL2 gene as a
      functional homologue of BUL1. The bul1 bul2 double disruptant was sensitive to
      various stresses, such as high temperature, salts, and a non-fermentable carbon
      source. Each Bul protein has a putative PY-motif that has been predicted to
      interact with one of three WW-domains of Rsp5. A mutant Bul1 containing an
      altered PY-motif was defective in ability to bind to Rsp5 in the two-hybrid
      system and hardly co-immunoprecipitated with Rsp5. Furthermore, the mutant was
      not able to overcome all growth defects of the double disruptant. Thus, Bul
      proteins are essential for growth in various stress conditions, and their
      functions are mediated through the PY-motif, probably by binding to Rsp5.

PMID- 9931425
TI  - Structures of mouse Rep-8 cDNA and genomic clones.
AB  - A mouse homologue of the human Rep-8 gene was cloned by PCR methods using
      degenerate oligonucleotide primers corresponding to highly conserved regions
      between human and mouse genes, and by the Marathon-Ready cDNA amplification
      method. The full-length mouse Rep-8 contains 1422 nucleotides and codes for a
      protein of 277 amino acids with a calculated mol. wt. of 31,519. The overall
      amino acid sequence homology between mouse and human Rep-8 proteins was 73%, and
      the overall nucleic acid sequence similarity was 65%. The predicted amino acid
      sequence of mouse Rep-8 has leucine zipper-like motifs in the N-terminal region,
      similar to the human Rep-8 protein. Rep-8 exists as a single-copy gene and is
      expressed in both the early and late embryonic stages of mouse development,
      suggesting that the Rep-8 gene product has an important role in embryogenesis.
      The genomic structure of the mouse Rep-8 gene was characterized extensively so
      that a gene targeting strategy could be used to develop an understanding of the
      biological function(s) of this interesting gene and its product.

PMID- 9931426
TI  - High-level expression of soluble heterologous proteins in the cytoplasm of
      Escherichia coli by fusion to the bacteriophage lambda head protein D.
AB  - The bacteriophage Lambda head protein D (gpD) is a small major capsid protein
      (110aa; 11.6kDa; pI=5.68, devoid of cysteine residues) that is essential for
      stable head morphogenesis. We found that a His-tagged derivative of gpD (gpHD) is
      a monomeric protein with efficient expression properties and high resistance
      towards thermally induced irreversible aggregation. In addition, gpHD can be used
      as a fusion partner for high-level expression of soluble heterologous proteins in
      the cytoplasm of Escherichia coli. Its broad utility is illustrated by the
      production of various mammalian proteins by fusion to its C-terminus. As a fusion
      partner, gpHD is thought to mediate optimal translation initiation while reducing
      inclusion body formation and protein degradation. In addition, it provides a His
      tag for simple purification. gpHD may act as a 'cytoplasmic anchor' by keeping
      its unfolded fusion partner in solution, thereby providing more time for proper
      folding. An ever-increasing number of open reading frames (ORFs) are being
      identified in the various genome sequencing programs. gpHD has the potential to
      be harnessed for the development of highly efficient cytoplasmic expression
      systems that might contribute to the production and characterization of these
      novel polypeptides. Protein D is also an established fusion partner for phage
      display. It thus presents the attractive opportunity of coupling the selection of
      heterologous proteins from a phage library to their subsequent high-level
      expression.

PMID- 9931427
TI  - Identification of CYP3A4 as the major enzyme responsible for 25-hydroxylation of
      5beta-cholestane-3alpha,7alpha,12alpha-triol in human liver microsomes.
AB  - Human liver microsomes catalyze an efficient 25-hydroxylation of 5beta-cholestane
      3alpha,7alpha,12alpha-triol. The hydroxylation is involved in a minor,
      alternative pathway for side-chain degradation in the biosynthesis of cholic
      acid. The enzyme responsible for the microsomal 25-hydroxylation has been
      unidentified. In the present study, recombinant expressed human P-450 enzymes
      have been used to screen for 25-hydroxylase activity towards 5beta-cholestane
      3alpha, 7alpha,12alpha-triol. High activity was found with CYP3A4, but also with
      CYP3A5 and to a minor extent with CYP2C19 and CYP2B6. Small amounts of 23- and 24
      hydroxylated products were also formed by CYP3A4. The Vmax for 25-hydroxylation
      by CYP3A4 and CYP3A5 was 16 and 4.5 nmol/(nmolxmin), respectively. The Km was 6
      microM for CYP3A4 and 32 microM for CYP3A5. Cytochrome b5 increased the
      hydroxylase activities. Human liver microsomes from ten different donors, in
      which different P-450 marker activities had been determined, were incubated with
      5beta-cholestane-3alpha,7alpha, 12alpha-triol. A strong correlation was observed
      between formation of 25-hydroxylated 5beta-cholestane-3alpha,7alpha,12alpha-triol
      and CYP3A levels (r2=0.96). No correlation was observed with the levels of
      CYP2C19. Troleandomycin, a specific inhibitor of CYP3A4 and 3A5, inhibited the 25
      hydroxylase activity of pooled human liver microsomes by more than 90% at 50
      microM. Tranylcypromine, an inhibitor of CYP2C19, had very little effect on the
      conversion. From these results, it can be concluded that CYP3A4 is the
      predominant enzyme responsible for 25-hydroxylation of 5beta-cholestane-3alpha,
      7alpha,12alpha-triol in human liver microsomes.

PMID- 9931429
TI  - Down-regulation of beta1,4-galactosyltransferase gene expression by cell-cycle
      suppressor gene p16.
AB  - Beta1,4-Galactosyltranferase (beta1,4GT, EC 2.4.1.38) is one of the key enzymes
      controlling the biosynthesis of complex-type oligosaccharides, and is also one of
      the best-studied glycosyltransferases. To study the molecular mechanisms involved
      in the regulation of beta1,4GT gene expression, we transfected cell-cycle
      suppressor gene p16 into A549 cell line (in which p16 is deleted), measured
      beta1,4GT gene expression by Northern blot hybridization, and evaluated its
      activity. It was found that p16 could down-regulate beta1,4GT gene expression and
      its activity. However, p16 decreased cell surface beta1,4GT activity more than
      total activity. beta1,4GT mRNA stability was also assayed. It was found that p16
      could not influence beta1,4GT mRNA stability.

PMID- 9931428
TI  - Expression cloning in Fe2+ transport defective yeast of a novel maize MYC
      transcription factor.
AB  - A complementation approach of the yeast fet3fet4 mutant strain, defective in both
      low- and high-affinity iron transport, was initiated as an attempt to
      characterize the Fe(III)-mugineic acid (MA) transporter from grasses. A maize
      cDNA encoding a novel MYC transcription factor, named 7E, was cloned by screening
      an iron-deficient maize root cDNA expression library on a minimum media
      containing Fe(III)-deoxyMA as a unique iron source. 7E expression restored growth
      specifically to the fet3 fet4 mutant strain. It did not affect growth rate of a
      trk1trk2 potassium transport defective yeast strain or parental W303 strain
      growth rate. No 55Fe uptake increase was observed in 7E transformed fet3 fet4
      yeast during short-term kinetics. However, the iron accumulation in these cells
      was 1.3-fold higher than in untransformed cells after a 24-h period. The 7E
      protein contained 694 amino acids and had a predicted molecular mass of 74.2kDa.
      It had 44% identity with the RAP-1 protein, a 67.9-kDa MYC-like protein from
      Arabidopsis thaliana which binds the G-box sequence via a basic region helix-loop
      helix (bHLH), without requiring heterodimerization with MYB proteins. Phylogenic
      comparisons revealed that the maize 7E protein was related to the Arabidopsis
      thaliana RAP-1 protein and to the Phaseolus vulgaris PG1. This similarity was
      particularly evident for the bHLH domain, which was 95% identical between maize
      7E and Arabidopsis thaliana RAP-1. 7E, RAP-1 and PG-1 proteins revealed a plant
      MYC-like sub-family that was more related to the maize repressor-like IN1 than to
      maize R proteins. 7E mRNA was detected in both roots and leaves by the Northern
      analysis. The amount of 7E mRNA increased, in response to iron starvation, by 20
      and 40% in roots and leaves, respectively. The relationship between iron
      metabolism and myc expression in animal cells is discussed.

PMID- 9931430
TI  - Selectable in-vivo recombination to increase antibody library size--an improved
      phage display vector system.
AB  - Phage display technology permits the display of libraries of random combinations
      of light (LC) and heavy chain (HC) antibody genes. Maximizing the size of these
      libraries would enable the isolation of antibodies with high affinity and
      specificity. In this study, the loxP/Cre system of in-vivo recombination has been
      employed to construct an improved vector system for the display of antibodies. In
      this system, the chloramphenicol acetyl transferase (CAT) gene is linked to a HC
      library in a donor plasmid, pUX. This CAT gene is 'silent' before recombination
      but active after recombination. A second acceptor phagemid, pMOX, is used for
      cloning the LC repertoire. Following infection with a Cre producing phage, pMOX
      accepts the CAT/HC library from pUX via site-specific recombination at the loxP
      sites. Recombinants can then be selected via chloramphenicol resistance. Using
      this vector system, we have generated libraries of 4x109 recombinants.
      Restriction analysis and Fab expression confirmed that 100% of the colonies in
      the library were recombinants. This system provides a stable selectable mechanism
      for the generation of large libraries and avoids the isolation of non
      recombinants encountered with earlier in-vivo recombination systems.

PMID- 9931431
TI  - Identification of Ce-AF-6, a novel Caenorhabditis elegans protein, as a putative
      Ras effector.
AB  - Mammalian Ras proteins associate with multiple effectors, including Raf, Ral
      guanine nucleotide dissociation stimulator, phosphoinositide 3-kinase and AF-6.
      In the nematode Caenorhabditis elegans, LIN-45/Raf has been identified
      genetically as an effector of LET-60/Ras. To search for other effectors in C.
      elegans, we carried out a yeast two-hybrid screening for LET-60-associating
      proteins. The screening identified a novel protein, designated Ce-AF-6, which
      exhibited a strong structural homology with human AF-6, rat Afadin and Drosophila
      melanogaster Canoe and possessed both the Ras-associating (RA) domain and the PSD
      95/DlgA/ZO-1 (PDZ) domain. Ce-AF-6 associated with human Ha-Ras in a GTP
      dependent manner, with an efficiency comparable to that of human Raf-1 Ras
      binding domain. When the effects of mutations of the Ras effector region residues
      were examined for associations with various effectors, Ce-AF-6 was found to
      possess a distinct and the most rigorous requirement for the effector region
      residues. These results strongly suggest that Ce-AF-6 is a putative effector of
      Ras that possesses a distinct recognition mechanism for association with Ras.

PMID- 9931432
TI  - Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsion model
      in rats.
AB  - In previous studies, it was shown that lipid microemulsions resembling LDL (LDE)
      but not containing protein, acquire apolipoprotein E when injected into the
      bloodstream and bind to LDL receptors (LDLR) using this protein as ligand. Aiming
      to evaluate the effects of apolipoprotein (apo) B-100 on the catabolism of these
      microemulsions, LDE with incorporated apo B-100 (LDE-apoB) and native LDL, all
      labeled with radioactive lipids were studied after intraarterial injection into
      Wistar rats. Plasma decay curves of the labels were determined in samples
      collected over 10 h and tissue uptake was assayed from organs excised from the
      animals sacrificed 24 h after injection. LDE-apo B had a fractional clearance
      rate (FCR) similar to native LDL (0.40 and 0.33, respectively) but both had FCR
      pronouncedly smaller than LDE (0.56, P<0.01). Liver was the main uptake site for
      LDE, LDE-apoB, and native LDL, but LDE-apoB and native LDL had lower hepatic
      uptake rates than LDE. Pre-treatment of the rats with 17alpha-ethinylestradiol,
      known to upregulate LDLR, accelerated the removal from plasma of both LDE and LDE
      apoB, but the effect was greater upon LDE than LDE-apoB. These differences in
      metabolic behavior documented in vivo can be interpreted by the lower affinity of
      LDLR for apo B-100 than for apo E, demonstrated in in vitro studies. Therefore,
      our study shows in vivo that, in comparison with apo E, apo B is a less efficient
      ligand to remove lipid particles such as microemulsions or lipoproteins from the
      intravascular compartment.

PMID- 9931433
TI  - Cell type specificity of the human endoglin promoter.
AB  - Endoglin is a component of the transforming growth factor-beta receptor complex
      whose expression is limited to a small number of cell types, including
      endothelial cells (ECs), activated monocytes, tissue macrophages and erythroid
      precursors. Of particular interest is its preferential expression in the
      vasculature of many malignant tumors, especially in view of potential therapeutic
      applications. We have cloned the human endoglin promoter, analyzed its structure
      and demonstrate that the isolated genomic fragment shows strong promoter activity
      in ECs (compared to other known EC-selective promoters), but not in epithelial
      cells and fibroblasts. These findings suggest that the endoglin promoter may
      prove a useful tool for the transcriptional targeting of ECs by gene therapy. We
      also determined the domains that are responsible for both efficient transcription
      and the observed preferential activity in ECs. The region around the major site
      of transcription initiation was found to be essential for transcription in both
      ECs and non-ECs. In contrast, cell type specificity does not appear to be
      governed by a single mechanism, but rather seems to be due to functionally
      distinct regulatory mechanisms acting on different upstream sequences.

PMID- 9931434
TI  - A unique isoform of phospholipase Cbeta4 highly expressed in the cerebellum and
      eye.
AB  - We report a unique isoform of PLCbeta4 in rat, PLCbeta4c, that has an additional
      37-nucleotide exon inserted between nucleotides 3459-3460 of the previously
      published PLCbeta4a coding sequence. This insertion results in replacement of 22
      amino acid residues at the carboxyl terminal tail of PLCbeta4a with 41 unique
      residues. A human EST for PLCbeta4 also contains this exon and this exon was
      mapped to within a 5.5 kb intron of the human PLCbeta4 gene. PLCbeta4c is the
      third PLCbeta4 isoform to be identified which has a unique carboxyl-terminal
      tail. PLCbeta4b differs from PLCbeta4a by truncation 162 amino acid residues from
      the carboxyl terminus which are replaced with 10 distinct amino acid residues.
      Reverse transcription-polymerase chain reaction experiments show that both
      PLCbeta4a and PLCbeta4c mRNA are expressed throughout the rat brain and that
      PLCbeta4c mRNA is highly expressed in the eye and cerebellum. RNase protection
      assays demonstrate that both PLCbeta4a and PLCbeta4c transcripts are abundant in
      the cerebellum. The different carboxyl terminal tails of PLCbeta4 isoforms may
      allow for differential targeting and subcellular localization, contributing to
      regulation of PLC beta4-mediated signal transduction.

PMID- 9931436
TI  - Structure and organization of the genes encoding mouse small proline-rich
      proteins, mSPRR1A and 1B.
AB  - Two genomic clones comprising the entire coding sequence of mouse SPRR1A and 1B
      genes were isolated and sequenced. Sequence analysis of the 1A and 1B genomic
      clones indicated that both genes contain two exons separated by an intron
      slightly larger than 1.1kb in size (1147 and 1152nt, respectively). This type of
      genomic structure is identical to the counterpart of human SPRR1 gene and other
      genes encoding for cornified envelope proteins. Primer extension analysis using
      1A and 1B gene-specific primers indicates that 1A gene is expressed in squamous
      tissues such as skin and esophagus, whereas 1B gene is expressed in papilloma
      tumors but not in squamous tissues. The first 300nt of 5'-flanking region of the
      mouse SPRR 1A and 1B genes reveal an overall approximately 50% identity to the
      human counterpart. However, there is a high degree of identity (?75%) at the
      promoter region containing a TATA box and TRE/TRE-like motifs. Both TATA and
      TRE/TRE-like motifs are almost identical in sequence and positions to those found
      in the counterpart of human promoter. Using transient transfection for the
      analysis of promoter activity, we observed that both 1A and 1B 5'-flanking
      regions contain the promoter activity to direct the expression of the reporter
      gene, chloramphenicol acetyltransferase, in airway epithelial cells in a fashion
      similar to that observed in the human counterpart. These results indicate a
      conserved nature of genetic structure and regulation of SPRR1 gene expression
      between human and mouse.

PMID- 9931435
TI  - Identification, characterization and mapping of the human ZIS (zinc-finger,
      splicing) gene.
AB  - From a human fetal brain cDNA library, we isolated two transcripts (ZIS-1 and ZIS
      2) corresponding to the human ZIS gene, an ortholog of the rat Zis (zinc finger,
      splicing). A comparison of base sequences of the cDNA and its corresponding
      genomic DNA (a P1-derived artificial chromosome clone) revealed that both
      transcripts have an ORF of 1011bp and encodes 337 amino acids, but ZIS-1 has 10
      exons and ZIS-2 contains 11 exons. Although both transcripts share the first nine
      exons, exon 10 of ZIS-2 is lacking in ZIS-1, and instead, exon 11 (10th exon) of
      ZIS-1 is larger in size, leading to the longer 3'-UTR. Thus, the two transcripts
      result from differential splicing. A Northern blot analysis on various adult and
      fetal tissues revealed that 5.2- and 3.2-kb transcripts were ubiquitously
      expressed, and 3.9- and 1.9-kb transcripts were highly expressed in the fetal
      brain and kidney, respectively. There were several other transcripts that may be
      alternatively processed forms of the human ZIS. Considering the ZIS gene size,
      the 3.2-kb transcripts most likely corresponds to ZIS-1 and may act as a major
      transcript of ZIS. The human ZIS has a high homology to the rat Zis for the
      coding DNA sequence with 91% identity and for the amino acid sequence with 87%
      identity. ZIS and Zis contain the same numbers of exons and introns. Both genes
      have unusually long 3'-UTR, and their encoding proteins contain similar
      components, i.e. a zinc finger domain, a nuclear localization signal, an Asp-Glu
      region, and a Ser-Arg-rich region. Furthermore, the expression patterns of the
      two genes in tissues are similar each other. Thus, the human ZIS may act as a
      transcriptional factor to regulate transcription and/or splicing, as does the rat
      Zis.

PMID- 9931437
TI  - Analysis of the 5' and 3'UTRs in the post-transcriptional regulation of the
      interleukin-5 gene.
AB  - Post-transcriptional regulation is emerging as an important control point in
      cytokine gene expression. However, the role that it plays in IL-5 gene expression
      is unclear with some conflicting reports. Here we investigate the importance of
      post-transcriptional regulation and the role of the 5' and 3' untranslated
      regions (UTRs) in mIL-5 gene expression. To do this, IL-5 expression from a panel
      of cDNA constructs was compared. We found it essential to remove the 5' synthetic
      oligonucleotide tails, introduced during the cloning of the mIL-5 cDNA, when
      studying IL-5 expression. The presence of these oligo(G) tails acted as potent
      inhibitors of translation of both SV40 and SP6 transcripts. Furthermore, the
      length of the tails was found to be critical to the translational efficiency.
      Taking this into account, we found no evidence to suggest that IL-5 is regulated
      at the level of mRNA stability or translation efficiency by either the 5' or
      3'UTR. These results suggest that post-transcriptional control is not a major
      factor regulating IL-5 expression.

PMID- 9931439
TI  - Cloning, mRNA localization and evolutionary conservation of a human 5-HT7
      receptor pseudogene.
AB  - Initial experiments designed to clone novel serotonin receptor subtypes in the
      substantia nigra have led to the discovery of a transcribed human 5-HT7 receptor
      pseudogene that is expressed in a wide range of tissues. The original clone
      (S771) possessed greater than 90% homology to the 5-HT7 receptor sequence and was
      identified by a degenerate PCR approach. Expression of the pseudogene transcript
      was detected throughout the brain and peripheral tissues in general agreement
      with 5-HT7 mRNA localization. Interestingly, the transcript was detected in
      tissues not known to express the 5-HT7 receptor (i.e. liver and kidney). Analysis
      of genomic DNA explained the genesis of the human pseudogene via a processed
      parental transcript (retrotransposition) and led to the discovery of a species
      homologue in the rhesus monkey.

PMID- 9931438
TI  - Trout thrombocytes contain 12- but not 5-lipoxygenase activity.
AB  - Fish thrombocytes are thought to be the evolutionary forerunners of mammalian
      platelets. Thrombocyte preparations made by conventional methods, such as density
      gradient centrifugation, contain other cell types such as neutrophilic
      granulocytes and lymphocytes that could interfere with subsequent experiments. In
      this study, rainbow trout thrombocytes were separated by density gradient
      centrifugation and further purified by magnetic cell sorting (MACS) using the
      thrombocyte specific monoclonal antibody, 30D8. Thrombocyte purity was assessed
      by reactivity to 30D8 using flow cytometry and immunocytochemistry. Following
      purification by density gradient centrifugation, thrombocytes were 66.9+/-9.2%
      (mean value+/-S.E.M., n=3) pure. Further purification by MACS significantly
      increased thrombocyte purity to 97.3+/-0.6%, whereas only 1.4% of the MACS -ve
      fraction were identified as these cells. Incubation of thrombocytes isolated by
      density gradient alone with calcium ionophore, A23187, generated a range of
      eicosanoids derived from arachidonic or eicosapentaenoic acids, namely,
      leukotriene (LT)B4, LTB5, lipoxin (LX)A4, LXA5, 12-hydroxyeicosatetraenoic acid
      (12-HETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE). A similar eicosanoid
      generation profile was observed for cells in the MACS -ve fraction; however, MACS
      +ve cells (thrombocytes) generated no 4 or 5 series LT or LX but did generate
      significant amounts of the 12-lipoxygenase (LO) products, 12-HETE and 12-HEPE.
      These results indicate that trout thrombocytes contain no demonstrable 5-LO
      activity and like their mammalian counterparts possess 12-LO activity.

PMID- 9931440
TI  - Identification and molecular characterization of a gene homologous to epr
      (endopeptidase resistance gene) in Staphylococcus aureus.
AB  - Certain Staphylococci possess a gene called epr or lif that renders the cells
      resistant to lysis by glycylglycine endopeptidase. The resistance is conferred by
      modifying the amino acid composition of interpeptide chains in cell-wall
      peptidoglycan by increasing serine content and decreasing glycine content. A gene
      homologous to epr/lif was cloned from S. aureus RN450 genomic libraries and
      designated eprh. eprh was found to localize 27bp downstream of a novel cell-wall
      hydrolase gene lytN, which is in the same orientation with eprh. By analogy with
      epr/lif, eprh is suggested to be involved in the transfer of certain amino acids,
      possibly serine or amino acids other than glycine, to interpeptide chains of cell
      wall peptidoglycan. Unlike epr/lif, overexpression of eprh in S. aureus did not
      result in an increased resistance to lysostaphin. Insertional inactivation of
      eprh or lytN by Campbell-type integration did not affect the susceptibility of
      the cells to lysostaphin, either. These results suggest that eprh and lytN are
      not essential genes for S. aureus growth. The physiological function of eprh
      remains unknown.

PMID- 9931441
TI  - TIMP-1 expression is increased in X-linked progressive retinal atrophy despite
      its exclusion as a candidate gene.
AB  - X-linked progressive retinal atrophy (XLPRA) is the only known natural animal
      model for X-linked retinitis pigmentosa (XLRP), a blinding disorder in man. The
      tissue inhibitor metalloproteinase 1 gene (TIMP-1), present in close proximity to
      one of the two XLRP loci, was tested as a candidate for XLPRA, by first
      characterizing the cDNA and gene from a normal dog. The cloned canine TIMP-1 cDNA
      is predicted to encode a protein of 207 amino acids with 66-83% identity in the
      deduced aa sequence with homologous mammalian genes. No sequence difference in
      the coding sequence of TIMP-1 was observed between normal and XLPRA-affected
      dogs. TIMP-1 was found to be expressed in all of the canine tissues examined by
      reverse transcription and polymerase chain reaction. The canine TIMP-1 spans
      3.5kb and is interrupted by five introns with sizes comparable to those observed
      in the human and mouse homologues of the gene. The proximal promoter region of
      canine TIMP-1 contains sequence motifs shown to have regulatory significance in
      transcription of human TIMP-1. Linkage analysis between XLPRA and TIMP-1 using a
      newly identified intragenic polymorphism identified recombinants, which
      conclusively excluded the gene as a candidate for the disease. TIMP-1 is
      overexpressed several months before retinal degeneration is histologically
      evident in XLPRA dogs, implying that alterations in interphotoreceptor matrix
      composition precede retinal degeneration by a significant time period.

PMID- 9931442
TI  - An isoform of Nurr1 functions as a negative inhibitor of the NGFI-B family
      signaling.
AB  - NGFI-B, Nurr1 and NOR-1 constitute a distinct subfamily within the nuclear
      receptor superfamily. To clarify the transcriptional regulation by the NGFI-B
      family, we searched for other components that can bind to the NBRE response
      element, a known target sequence for these transcription factors. By low
      stringency hybridization using the DNA binding domain of NOR-1 as a probe, a C
      terminal truncated Nurr1 isoform, named Nurr2, was isolated from a mouse MC3T3-E1
      cell cDNA library. Nurr2 had a novel cryptic exon located upstream in the Nurr1
      promoter region, and was generated by alternative splicing at exons 1, 2 and 6.
      The C-terminal region was encoded by frame-shifted exon 6, and so Nurr2 lacked
      the C-terminal sequences corresponding to the putative ligand binding domain or
      dimerization domain. Quantitative reverse transcriptase-PCR experiments confirmed
      the presence of the Nurr2 isoform in mouse, rat and human. It was, like Nurr1,
      highly expressed in the pituitary and the cerebral cortex. Nurr2 and Nurr1 were
      also concomitantly induced by forskolin in NIH3T3 cells. Functional analysis
      using a reporter gene, containing NBRE response elements, indicated that while
      the isoform was inactive by itself, it could inhibit transactivation by the
      members of the NGFI-B family. These results indicate that the C-terminal
      truncated isoform, Nurr2, may act as a negative regulator of the NGFI-B family
      signaling.

PMID- 9931443
TI  - Molecular cloning, chromosome mapping and characterization of the mouse CRTH2
      gene, a putative member of the leukocyte chemoattractant receptor family.
AB  - We have cloned the mouse CRTH2 (chemoattractant receptor-homologous molecule
      expressed on TH2 cells) gene encoding a putative leukocyte chemoattractant
      receptor, of which human homologue is expressed selectively in Th2 but not in Th1
      clones among T cell clones. The deduced amino-acid sequence of mouse CRTH2 bears
      77% identity with its human homologue. Phylogenetic analysis suggested that both
      mouse and human CRTH2 are closely related to the N-formyl peptide receptor and
      the C5a receptor among leukocyte chemoattractant receptors. The mouse CRTH2 gene
      was mapped on chromosome 19c with FISH, where no other genes for leukocyte
      chemoattractant receptors are mapped. RT-PCR analysis revealed that mouse CRTH2
      mRNA is expressed in various cell lineages, including both hematopoietic and non
      hematopoietic cell lines. Expression was also observed in liver, lung, kidney,
      brain, heart, thymus, and spleen. These results suggest that mouse CRTH2
      functions in a variety of cells, making the effects of CRTH2 pleiotropic.

PMID- 9931444
TI  - Ubiquitin-proteasome-dependent degradation of apolipoprotein B100 in vitro.
AB  - Apolipoprotein B100 (apoB) is a large secretory protein that forms very low
      density lipoprotein in liver. An in vitro degradation assay was developed using
      rabbit reticulocyte (RR) lysate in order to investigate the mechanism of
      intracellular degradation of newly synthesized apoB by the ubiquitin-proteasome
      pathway. [3H]apoB, isolated from [3H]leucine pulsed/chased Hep G2 cells, was
      degraded 51% when incubated for 2 h at 37 degreesC in an assay mixture that
      included RR lysate (source of the ubiquitin conjugation system and proteasome)
      and an exogenous ATP regenerating system. ApoB degradation was ATP-dependent and
      degradation fragments were not observed suggesting that the very large apoB
      molecule was extensively degraded. ApoB degradation was decreased to 50% when
      potent proteasome inhibitors, clasto-lactacystin beta-lactone (10 microM) or MG
      132 (50 microM), were added to the reaction mixture, but was not affected by the
      cysteine protease inhibitor, E-64, or the serine protease inhibitor,
      phenylmethylsulfonyl fluoride. ApoB degradation was inhibited by the mutant
      ubiquitin protein K48R and by ubiquitin aldehyde, an inhibitor of ubiquitin
      protein isopeptidases. During incubation ubiquitination of apoB increased even as
      apoB was being degraded. These results suggest that in vitro degradation of apoB,
      a large secretory protein that is normally found in the endoplasmic reticulum
      (ER) lumen or associated with the ER membrane, was proteasome-dependent and
      involved both ubiquitination and deubiquitination steps.

PMID- 9931445
TI  - Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted
      expression in cytotrophoblastic cells and heart.
AB  - The basic helix-loop-helix (bHLH) factor Hand1 plays a role in the developing
      chicken heart and is required for trophoblast giant cell differentiation and
      cardiac looping of mouse embryonic development. Here, we report the cloning of
      the human Hand1 cDNA and gene from a heart-specific cDNA library and a genomic
      lambda-DNA library, respectively. We present the nucleotide sequence of a 1.75kb
      cDNA clone, encoding the presumptive 215 amino acid human Hand1 protein, and show
      homology comparison of the conserved bHLH region between different species. In
      vitro transcription-translation of Hand1 mRNA and analysis of protein size
      suggest that the Hand1 polypeptide is (post)translationally modified. By Southern
      blot analysis we demonstrate that the isolated genomic DNA clone harbours the
      entire Hand1 gene and describe molecular structure and sequences of the two 799
      and 938bp exons and the single 1.56kb intron. The expression pattern of the mRNA
      in different human tissues revealed that Hand1 transcripts are restricted to the
      heart, suggesting that the protein could be required for cardiac-specific gene
      transcription and function in adults. Hand1 transcripts were undetectable in a
      non-tumorigenic villous trophoblast cell line, immunopurified cytotrophoblasts
      undergoing in vitro differentiation, and first trimester placental tissue,
      suggesting that the transcription factor is not involved in the development of
      villous and extravillous trophoblast cell lineages. Hand1 mRNA, however, was
      abundantly expressed in cytotrophoblastic Jeg-3 and BeWo cells, suggesting that
      Hand1 could be required for early trophoblast differentiation.

PMID- 9931446
TI  - Cloning, sequencing and characterization of the rat hereditary hemochromatosis
      promoter: comparison of the human, mouse and rat HFE promoter regions.
AB  - We have cloned and sequenced 1398bp of the rat HFE gene promoter region. The
      alignment of the rat promoter HFE sequence with the HFE promoter sequence from
      human and mouse detected several highly conserved sequences present at
      orthologous or heterologous positions in the three species. Subsequent analysis
      of the conserved promoter sequences identified the presence of 10 novel
      transcription elements present in the promoter regions of the human, mouse and
      rat HFE genes (GATA, NF-IL6, AP1, AP2, CREB, PEA3, gamma-IRE, GFI1, HNF-3beta,
      HFH2). Different gel retardation analyses performed with rat-liver nuclear
      extracts have confirmed the presence of factors binding to some of these
      transcription elements. This represents the first data concerning the
      identification of potential transcriptional elements of the HFE promoter in these
      three species. The expression pattern of the transcription factors corresponding
      to the novel elements identified in the HFE promoter is consistent with the
      potential role of the HFE promoter in the transcription regulation and function
      of the HFE gene. Knowledge of the identified conserved elements in the HFE
      promoter from human, mouse and rat provides the basis for subsequent in-vitro or
      in-vivo studies leading to identification of the detailed mechanisms involved in
      the regulation of the iron metabolism and the design of potential future
      alternative therapies.

PMID- 9931447
TI  - Recent amplification of the human FRG1 gene during primate evolution.
AB  - There is evidence of multiple copies of the FSHD Region Candidate Gene 1 (FRG1)
      in humans. Analysis of human FRG1 ESTs showed many of them to be non-processed
      pseudogenes dispersed throughout the genome. To determine when the amplification
      of FRG1 occurred, we used a PCR-based approach to identify FRG1 sequences from
      great apes, chimpanzee, gorilla and orang-utan, and an Old World monkey, Macaca
      mulatta. In common with humans, multiple copies of FRG1 were detected in the
      great apes. However, in Macaca mulatta, only two FRG1 loci were identified, one
      presumed to be the homologue of the human chromosome 4q gene. This is strikingly
      similar to the distribution of a dispersed 3.3-kb repeat family in primates. A
      member of this family, D4Z4, maps to the subtelomeric region of 4q, in close
      proximity to FRG1. We propose that an ancestral duplication of distal 4q included
      FRG1. This duplication is present in Macaca mulatta whose divergence from
      hominoids is thought to have occurred at least 33 million years ago. We propose
      that this telomeric region then underwent further amplification and dispersion
      events in the great ape lineage, with copies of FRG1 and the 3.3-kb repeats being
      localized in heterochromatic regions.

PMID- 9931448
TI  - Purification of ethanolaminephosphotransferase from bovine liver microsomes.
AB  - CDP-ethanolamine:diacylglycerol ethanolaminephosphotransferase (EC 2. 7.8.1) has
      been purified to electrophoretic homogeneity and in a catalytically active form
      from bovine liver microsomes. The purification method is based on the high
      hydrophobicity of the protein whose charged sites appear to be masked from the
      interaction with the chromatographic stationary phases when membranes are
      solubilized with an excess of non-ionic detergent. The isolated protein has a
      molecular mass of about 38 kDa, as estimated by SDS-PAGE mobility, and exhibits
      both ethanolaminephosphotransferase and cholinephosphotransferase activities.
      Evidence is given that both activities are Mn2+-dependent and that the same
      catalytic site is involved in cholinephosphotransferase and
      ethanolaminephosphotransferase reactions. Mg2+-dependent CDP
      choline:diacylglycerol cholinephosphotransferase (EC 2.7.8.2) is completely
      inactivated during the solubilization and purification steps.

PMID- 9931449
TI  - The Streptomyces aureofaciens homologue of the sporulation gene whiH is dependent
      on rpoZ-encoded sigma factor.
AB  - Using the method for the identification of promoters recognized by a sporulation
      specific sigma factor RpoZ, we identified a promoter in Streptomyces
      aureofaciens, directing expression of a gene having high sequence similarity (83%
      amino acid identity) to sporulation transcription factor WhiH of Streptomyces
      coelicolor. High-resolution S1-nuclease mapping using RNA prepared from S.
      aureofaciens from various developmental stages showed high similarity of PwhiH
      promoter to the consensus sequence of flagellar and chemotaxis promoters. The
      promoter was induced at the time of aerial mycelium formation, and was off in S.
      aureofaciens strain with rpoZ-disrupted gene. The results suggest that the PwhiH
      promoter is recognized by sigma factor RpoZ in S. aureofaciens.

PMID- 9931450
TI  - Transcriptional regulation by butyrate of mouse galectin-1 gene in embryonal
      carcinoma cells.
AB  - Endogenous galactoside-binding lectins (galectins) have been implicated in cell
      adhesion, growth, differentiation, neoplastic transformation, and metastasis.
      Galectin-1 (gal-1), one member of this family, has been best characterized. We
      isolated a DNA clone containing the gal-1 gene from mouse genomic libraries, and
      the sequence of the 5' upstream region up to -2430 bp was determined. Our
      previous study showed that sodium butyrate (butyrate) induced expression of gal-1
      at both mRNA and protein levels in the murine embryonal carcinoma (EC) cell line
      PCC4.aza1R and the induction of gal-1 by butyrate in PCC4.aza1R cells is at least
      partially regulated at transcriptional level. To locate the region which is
      responsible for the induction of gal-1 by butyrate, transient transfection of
      PCC4.aza1R cells with a series of gal-1 promoter/CAT chimeric gene, which have
      different deletions of the 5' region of the gal-1 promoter, showed that this 2430
      bp sequence is a butyrate-inducible promoter, and butyrate-inducible ability
      remained when only a 62 bp sequence ahead of the transcription site (+1) existed.
      The sequence from -62 to -41 which contains an Sp1 site at -57 was important for
      the induction of gal-1 expression by butyrate. Gel shift assay indicated that
      transcription factor SP1 actually bound to that Sp1 site. The changes of two
      nucleotides within that Sp1 site, from GG to TT, abolished the nuclear proteins
      binding to that Sp1 site as well as the response to butyrate. These results
      suggest that the 5' proximal Sp1 site at -57 is crucial for the butyrate-induced
      expression of the gal-1, and the direct binding of SP1 to this Sp1 site may be
      involved in this induction.

PMID- 9931451
TI  - Isolation and characterization of the human X-arrestin gene.
AB  - Arrestins are signal transduction modulators that quench the activated state of
      receptors. X-arrestin (ARRX) is specifically expressed in the red-, green-, and
      blue-sensitive cone photoreceptors, and is most likely a modulator of cone
      phototransduction. The human gene for X-arrestin at Xcen-Xq22 has been shown to
      be approximately 20kb in size and to consist of 17 exons and 16 introns. The
      exons are generally small, including exon 16 of 10bp, and are clustered into
      three groups, separated by the two largest introns. This gene structure is
      generally similar to that of S-antigen, the rod photoreceptor arrestin. There is
      remarkable similarity, however, among the individual exons between the two genes
      in that 10 of the exons are identical in size. The 5' upstream region of the X
      arrestin gene contains TATA and CAAT boxes, typical of genes expressed in a
      tissue-specific manner, in contrast to the S-antigen gene, which lacks these
      promoter sequences. The promoter elements, common to both the X-arrestin and S
      antigen genes, include the Ret-1/PCE-1 (PCE-1-like in X-arrestin), CRX, and the
      thyroid hormone/retinoic acid-responsive sequences, the former two being present
      in a number of photoreceptor-expressed genes. Three CRX-binding elements, 15bp
      apart, are present in a cluster. The common promoter elements between the cone
      expressed genes, X-arrestin and color opsins, include the TATA box, PCE-1, and
      CRX-binding sequences, the combination of which might be important for directing
      cone-specific expression.

PMID- 9931452
TI  - Expression and cDNA cloning of porcine peroxisome proliferator-activated receptor
      gamma (PPARgamma).
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      PPAR subfamily of nuclear hormone receptors. In rodents and humans, expression of
      PPARgamma is predominantly found in adipose tissue where it regulates adipocyte
      differentiation and the expression of multiple adipocyte genes. The primary aim
      of this work was to clone the porcine PPARgamma cDNA and examine the regulation
      of gene expression in porcine subcutaneous adipose tissue. The porcine PPARgamma
      gene encodes a 1.8-kb mRNA transcript and shares 99, 96 and 97% amino acid
      sequence identity to the human, mouse and cow PPARgamma molecules, respectively.
      Both isoforms of PPARgamma (gamma1 and gamma2) are highly expressed in porcine
      adipose tissue. The gamma2 isoform is expressed in low abundance in porcine
      spleen, whereas the gamma1 isoform is highly expressed in spleen and lung and at
      a low abundance in several other tissues. Western blot analysis confirmed a high
      level of PPARgamma protein expression in porcine adipose tissue compared to other
      tissues. Both caloric restriction and fasting significantly reduced PPARgamma2
      but not gamma1 mRNA and PPARgamma protein abundance in subcutaneous adipose
      tissue compared to ad-libitum fed controls. We provide the first evidence that
      PPARgamma is abundantly expressed in porcine subcutaneous adipose tissue, and
      that expression is regulated by caloric intake. Thus, PPARgamma may play an
      important role in adipogenesis and hormone action in porcine adipocytes.

PMID- 9931453
TI  - Comparative analysis of three murine G-protein coupled receptors activated by
      sphingosine-1-phosphate.
AB  - The cloning and analysis of the first identified lysophosphatidic acid (LPA)
      receptor gene, lpA1 (also referred to as vzg-1 or edg-2), led us to identify
      homologous murine genes that might also encode receptors for related
      lysophospholipid ligands. Three murine genomic clones (designated lpB1, lpB2, and
      lpB3) were isolated, corresponding to human/rat Edg-1, rat H218/AGR16, and human
      edg-3, respectively. Based on the amino acid similarities of their predicted
      proteins (44-52% identical), the three lpB genes could be grouped into a separate
      G-protein coupled receptor subfamily, distinct from that containing the LPA
      receptor genes lpA1 and lpA2. Unlike lpA1 and lpA2, which contain multiple coding
      exons, all lpB members contained a single coding exon. Heterologous expression of
      individual lpB members in a hepatoma cell line (RH7777), followed by 35S
      GTPgammaS incorporation assays demonstrated that each of the three LPB receptors
      conferred sphingosine-1-phosphate-dependent, but not lysophosphatidic acid
      dependent, G-protein activation. Northern blot and in situ hybridization analyses
      revealed overlapping as well as distinct expression patterns in both embryonic
      and adult tissues. This comparative characterization of multiple sphingosine-1
      phosphate receptor genes and their spatiotemporal expression patterns will aid in
      understanding the biological roles of this enlarging lysophospholipid receptor
      family.

PMID- 9931455
TI  - GT1b in human metastatic brain tumors: GT1b as a brain metastasis-associated
      ganglioside.
AB  - We studied ganglioside expression in 12 human metastatic brain tumors
      metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1),
      and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in
      brain metastatic tumor tissues, and GT1b was also present in all the metastatic
      brain tumor tissues. The latter was identified by TLC-immunostaining and
      characterized structurally by secondary ion mass spectrometry combined with 'Far
      Eastern blot'. The immunohistochemical analysis of frozen tissue sections
      confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was
      shown to be expressed both in the primary colon carcinoma and the metastasis of a
      single patient by immunohistochemical procedure. In systemic carcinomas without
      brain metastasis, GM3 was a common major component, but no GT1b was detected.
      These findings indicate that GT1b is a brain metastasis-associated ganglioside.
      We speculate that the presence of GT1b would be a useful marker for estimating
      metastatic potentials to the brain.

PMID- 9931454
TI  - Cloning and characterization of 5'-flanking region of mouse non-selective cation
      channel 1.
AB  - We have previously cloned mouse non-selective cation channel 1 (mNSC1) cDNA
      inducing cation current, from a mouse insulin secreting beta-cell line, MIN6. The
      current has characteristics of the Ca2+-activated non-selective (CAN) cation
      channel, and the mRNA is localized in the brain, heart, and lung. To understand
      the molecular mechanisms of the transcriptional regulation, we have cloned and
      characterized the 5'-flanking region of mNSC1. By the PCR method, we obtained 987
      bp of mouse genomic fragment. The computer program-based analysis revealed that
      it contained several consensus motifs; insulin responsive element (IRE), AP-2,
      PEA3, and GC box-like region. But there were neither typical TATA box nor CAAT
      box. Primer extension analysis and RNase protection assay were performed to
      identify the transcription start site. Transient transfection analyses using a
      series of 5'-end deletion and reporter gene constructs with CHO and LA-4 cells
      demonstrated some relatively active regions. The significantly active border
      correlated with IRE consensus with CHO cells. This observation may support that
      CAN current is activated by insulin.

PMID- 9931456
TI  - Selection of a cDNA clone for chicken high-mobility-group 1 (HMG1) protein
      through its unusually conserved 3'-untranslated region, and improved expression
      of recombinant HMG1 in Escherichia coli.
AB  - Screening of cDNA libraries for the homologous vertebrate proteins high mobility
      group (HMG) 1 and 2 using DNA probes based on the coding sequences is likely to
      result in isolation of both HMG1 and HMG2 clones, as well as pseudogenes, which
      may be transcribed at low levels. However, the 3'-untranslated regions (UTRs) of
      HMG1 and 2 are quite distinct, and unusually conserved across species. We have
      used this property to select the true chicken HMG1 cDNA clone from a chicken
      lymphocyte cDNA library in lambdagt11, using a probe based on the 3'-UTR of rat
      HMG1 cDNA. The chicken HMG1 cDNA clone is very similar to all the complete HMG1
      cDNA clones isolated so far. We suggest that the sequence designated chicken HMG1
      in the GenBank Data Library (Accession number D14314) is, in fact, that of HMG2a
      [and moreover that the recently reported mouse clone (Accession number AF022465),
      proposed to encode a new HMG protein, HMG4, is also likely to encode an HMG2a,
      based on the translated amino-acid sequence and 3'-UTR]. We also report much
      improved expression of intact recombinant HMG1 in Escherichia coli by the use of
      chloramphenicol rather than ampicillin selection and conditions that limit cell
      growth. This should be general for all members of the HMG1 (and 2) family which
      may be toxic to cells (possibly because of the long acidic tail), and may also
      prove useful in the production of other such proteins.

PMID- 9931458
TI  - GFP vectors for controlled expression and dual labelling of protein fusions in
      Bacillus subtilis.
AB  - We report the development of a series of plasmid vectors for the construction of
      fusions to mutants of the intrinsically fluorescent green fluorescent protein,
      GFPmut1 (Cormack et al., 1996. Gene 173, 33-38) and GFPuv (Crameri et al., 1996.
      Nature Biotechnology 14, 315-319). Both N- and C-terminal fusions can be
      produced, and their expression can be finely controlled from the inducible Pxyl
      promoter following double crossover integration into the amyE locus of the
      Bacillus subtilis chromosome. Other vectors designed for single crossover
      insertion into the chromosome allow downstream genes to be placed under inducible
      control. We also show that fusions to GFPmut1 and GFPuv can be co-localized
      within the cell by virtue of their different excitation spectra.

PMID- 9931457
TI  - Exon-I is involved in positive as well as negative regulation of human
      angiotensinogen gene expression.
AB  - Angiotensinogen is the glycoprotein precursor of one of the most potent
      vasoactive hormones, angiotensin-II. Angiotensinogen gene is primarily expressed
      in the liver, and this gene locus is linked with human essential hypertension. We
      show here that a mutation in exon-I reduces the basal expression of the human
      angiotensinogen gene in liver cells. We also show that a nucleotide sequence in
      exon-I binds to liver-enriched transcription factor HNF-3 and a ubiquitous factor
      AP4. Our studies also show that transient transfection of an expression vector
      containing AP4 coding sequence downregulates the expression of reporter
      constructs containing human angiotensinogen gene promoter. By contrast, co
      transfection of an expression vector containing HNF-3beta coding sequence
      increases the expression of these reporter constructs. The human angiotensinogen
      gene has a C/A polymorphism located at -20, and we have shown that estrogen
      receptor-alpha binds to this sequence when nucleoside A is present at this site.
      We show here that co-transfection of an expression vector containing AP4 coding
      sequence reduces estrogen-induced promoter activity of reporter constructs
      containing human angiotensinogen gene promoter (with nucleoside A at -20)
      attached to the CAT gene. These studies partly explain the molecular mechanisms
      involved in tissue-specific expression of the human angiotensinogen gene.

PMID- 9931459
TI  - Cloning of the 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-2 gene in the
      baboon: effects of estradiol on promoter activity of 11beta-HSD-1 and -2 in
      placental JEG-3 cells.
AB  - In the baboon, estrogen regulated 11beta-hydroxysteroid dehydrogenase (11beta
      HSD) catalyzed metabolism of cortisol and cortisone by the placenta is an
      important component in the sequence of events regulating the fetal pituitary
      adrenocortical axis. The present study was designed to isolate and sequence the
      promoter region of the baboon 11beta-HSD-2 gene and to produce constructs of this
      gene and the 1.7 kb fragment of 5'-flanking region of baboon 11beta-HSD-1
      isolated previously in order to determine whether the promoters of these two
      genes were activated in human placental JEG-3 cells and whether expression could
      be modulated by estradiol. The 11beta-HSD-2 genomic DNA was isolated from a
      baboon kidney genomic library using a human 11beta-HSD-2 cDNA as a probe. The
      sequence of a 1.2 kb fragment of the 5'-flanking region showed extensive homology
      with that published by others for human 11beta-HSD-2, particularly in exon 1
      (>95%) and in the proximal promoter (>90%). Primer extension confirmed that the
      baboon 11beta-HSD-2 gene has multiple transcriptional start sites which are
      preceded by a GC box. To determine promoter activity of 11beta-HSD-2 and -1, the
      5'-flanking regions of these genes were subcloned into luciferase reporter pGL3
      vectors, transiently transfected into human placental JEG-3 cells, and then
      incubated for 16-18 h in the presence or absence of 10-8 M 17beta-estradiol or
      17alpha-estradiol. To augment the low level of estrogen receptor (ER) in JEG
      cells, promoter activity studies were also performed in JEG cells co-transfected
      with an expression vector containing the human ER cDNA. The promoters of both
      11beta-HSD-1 and -2 were activated following transient transfection into JEG-3
      cells although basal activity of 11beta-HSD-2 (87+/-21 RLU/microg protein) always
      exceeded (P<0.05) that of 11beta-HSD-1 (37+/-7). In the absence of co-transfected
      ER, basal promoter activities of both 11beta-HSD genes were not altered by 17beta
      estradiol. In contrast, in cells co-transfected with ER, 17beta-estradiol but not
      17alpha-estradiol increased (P<0.05) basal promoter activities of 11beta-HSD-1
      and -2 by 8.1+/-1.5 and 8.3+/-2. 0 fold, respectively. Collectively, these
      findings indicate that the promoter region of the baboon 11beta-HSD-2 gene is
      comparable to that in the human and that the 5'-flanking region of both the
      baboon 11beta-HSD-1 and -2 genes were active when transiently transfected into
      JEG-3 cells and that activation could be enhanced by estradiol in the presence of
      an estrogen receptor.

PMID- 9931460
TI  - Isolation of hMRE11B: failure to complement yeast mre11 defects due to species
      specific protein interactions.
AB  - The Saccharomyces cerevisiae MRE11 gene plays an important role in meiotic
      recombination, mitotic DNA repair and telomere maintenance. We present the
      isolation of hMRE11B cDNA from a human HeLa cell cDNA library as an MRE11
      homolog. Compared to the previously identified hMRE11, hMRE11B contains an
      additional 84bp sequence that results in a 28 amino-acid insertion close to the C
      terminus. The expression pattern of hMRE11B in different tissues shows the
      presence of two mRNA species of approx. 2.6 and 7.5kb. Overexpression of hMRE11B
      does not complement the alkylation sensitivity of the mre11 null and temperature
      sensitive mutant strains. In this study, we examine factors that may explain this
      lack of complementation. First, both Northern and Western analyses rule out the
      lack of hMRE11B transcription and/or translation in yeast. Second, we demonstrate
      that hMre11B, like the yeast Mre11 protein, dimerizes in vivo in a yeast two
      hybrid system. This dimerization requires the C-terminal one-third of hMre11B
      protein, which includes the 28 amino acids absent in hMre11. However, hMre11B
      does not interact with Mre11, Rad50 and Xrs2. Hence, the lack of protein-protein
      interaction between hMre11B and the yeast Mre11, Rad50, and Xrs2 may explain the
      inability of hMRE11B to complement the yeast mre11 mutants. We rule out the
      hypothesis that the lack of interaction and, in turn of complementation, is due
      to the absence of sequence homology at the C-terminal domain of hMre11B compared
      to the yeast Mre11. Instead, we propose that the C-terminus of hMre11B
      participates in protein-protein interaction and functions in a species-specific
      manner.

PMID- 9931462
TI  - Physical map covering a 2 Mb region in human xp11.3 distal to DX6849.
AB  - A 2Mb contig was constructed of yeast artificial chromosomes (YACs) and P1
      artificial chromosomes (PACs), extending from DXS6849 to a new marker EC7034R,
      1Mb distal to UBE1, within the p11.3 region of the human X chromosome. This
      contig, which has on average four-fold cloned coverage, was assembled using 37
      markers, including 13 new sequence tagged sites (STSs) developed from YAC and PAC
      end-fragments, for an average inter-marker distance of 55kb. The inferred marker
      order predicted from SEGMAP analysis, STS content and cell hybrid data is Xpter
      EC7034R-EC8058R-FB20E11-DXS7804-D XS8308-(DXS1264, DXS1055)-DXS1003-UBE1-(UHX),
      PCTK1)-DXS1364-DXS1266-DXS337-SYN1-DXS6 849-cen. One (TC)n dinucleotide sequence
      from an end-clone was identified and found to be polymorphic (48%
      heterozygosity). The contig is merged with published physical maps both in the
      distal and in the centromeric direction of Xp, and provides reagents to aid in
      the DNA sequencing and the finding of genes in this region of the human genome.

PMID- 9931461
TI  - Structure of the gene encoding the ubiquitin-conjugating enzyme Ubcm4,
      characterization of its promoter, and chromosomal location.
AB  - Ubiquitin-conjugating enzymes (E2 or Ubc) play a key role in the post
      translational modification of proteins by ubiquitylation. They are encoded by a
      large family of genes that are closely related to each other. In this paper we
      present the first complete structural analysis, including the promoter and the
      chromosomal location, of a member of this family, the mouse Ubcm4 gene. At the
      genomic level the Ubcm4 gene spans approx. 50kb and is composed of four exons.
      Only about 1% of the total gene codes for amino acids. The four different Ubcm4
      specific RNAs encode the same protein and differ only in the length of the 3'
      untranslated region. The polyadenylation signals used by the four different RNAs
      are all within the 3' terminal exon. At the 5' end of the gene, multiple
      transcriptional start sites were mapped within a region of 25bp. The region
      proximal to the initiation sites does not contain a TATA box and is not GC-rich.
      Transient chloramphenicol acetyltransferase assays, however, showed that this
      region can promote the expression of a reporter gene and that 15bp upstream of
      the first initiation site were sufficient for basal expression. The Ubcm4 gene
      was mapped by interspecific backcross analysis to the proximal region of mouse
      chromosome 16.

PMID- 9931463
TI  - Structural analysis of human SCC antigen 2 promoter.
AB  - The squamous cell carcinoma antigen (SCCA) has been used as a circulating tumor
      marker for the management of squamous cell carcinoma. SCCA consists of a small
      gene family of at least two in human genome (SCCA1 and SCCA2), which are tandemly
      arrayed on chromosome 18q21.3 and share 92% identical residues. SCCA expressions
      are tightly controlled in a tissue-specific manner. To investigate the role of
      SCCA2 in the cancer cells, we first isolated the human genomic clones, containing
      the promoter region of SCCA2 gene, and determined the nucleotide sequence
      surrounding the exon 1. The transcription start site was mapped by primer
      extension analysis, and a putative TATA box element was found in the 5'-flanking
      region. Other putative regulatory sequences, which include Ets binding sequence,
      NF-IL6 binding sequence and IRE consensus sequence, were also found in the
      region. Analysis of luciferase reporter gene expression in transient transfection
      showed that the promoter region of SCCA2 gene was located within the region from 
      424 to +47.

PMID- 9931464
TI  - Identification of the gene structure and promoter region of H+-translocating
      inorganic pyrophosphatase in rice (Oryza sativa L. ).
AB  - In order to determine the gene structure and promoter region of vacuolar H+
      translocating inorganic pyrophosphatase (V-PPase), we isolated the genomic clones
      using a rice BAC library and probes derived from rice V-PPase cDNA (OVP1). The
      entire OVP1 gene is approx. 5.4 kb in length, and seven introns interrupt the
      coding sequence of OVP1. The first intron is extremely large (1869 bp), while the
      other introns are between 82 and 170 bp. A transcription initiation site,
      identified by a primer extension analysis, indicated the first exon to be 366 bp.
      A 1.1 kb fragment containing the 5'-flanking region of the first exon with the
      GUS reporter gene showed specific promoter activity in rice cells. These data
      show that the OVP1 gene is composed of eight exons and seven introns, and
      regulatory elements are present within 1.1 kb upstream from the first exon.

PMID- 9931465
TI  - Molecular cloning of Ras cDNA from Penaeus japonicus (Crustacea, decapoda):
      geranylgeranylation and guanine nucleotide binding.
AB  - A cDNA was isolated from the shrimp Penaeus japonicus by homology cloning. The
      shrimp hepatopancreas cDNA encodes a 187-residue polypeptide whose predicted
      amino acid sequence shares 85% homology with mammalian K-Ras 4B protein and
      demonstrates identity in the guanine nucleotide binding domains. Expression of
      the shrimp cDNA in Escherichia coli yielded a 21-kDa polypeptide with a positive
      reactivity towards the monoclonal antibodies against mammalian Ras. The GTP
      binding of the shrimp ras-encoded fusion protein was approximated to be
      30000units/mg of protein, whereas the binding for GDP was 5000units/mg of
      protein. Fluorography analysis demonstrated that the prenylation of both shrimp
      Ras GDP and shrimp Ras GTP by protein geranylgeranyltransferase I of shrimp
      Penaeus japonicus exceeded the shrimp Ras nucleotide-free form by 10-fold, and
      fourfold, respectively; that is, the shrimp protein geranylgeranyltransferase I
      prefers to react with the shrimp ras-encoded p25 fusion protein in the GDP-bound
      form.

PMID- 9931467
TI  - CpG doublets, CpG islands and Alu repeats in long human DNA sequences from
      different isochore families.
AB  - A computer analysis of 946 human DNA sequences larger than 50kb and representing
      about 118Mb of DNA has led to the following observations. (i) Positive
      correlations hold between CpG levels and the GC levels of isochores and coding
      sequences, as expected from previous results. (ii) The correlation between CpG
      levels and the GC levels of pseudogenes is characterized by lower CpG values (at
      comparable GC levels) and by a lower slope compared with the correlation with
      coding sequences; this finding suggests that an extensive methylation followed by
      deamination has taken place on CpG doublets from inactive genes leading to a
      further CpG shortage. (iii) The frequency of CpG islands in long human sequences
      increases with increasing GC and almost parallels gene frequency. (iv) The
      frequency of Alu sequences also increases with increasing GC, but attains a
      maximum in H2 isochores, in agreement with previous experimental data. (v) The
      ratio 5mC/CpG (namely, the methylation level over available sites) decreases with
      increasing GC levels of isochores. This decrease is due only to a small extent to
      the increase of (unmethylated) CpG islands in GC-rich isochores, and takes place
      in spite of the increase of strongly methylated Alu sequences in GC-rich
      isochores; this stresses the much lower relative methylation (5mC/CpG) of single
      copy sequences located in GC-rich isochores relative to those located in GC-poor
      isochores. (vi) CpG levels of Alus and CpG islands are positively correlated with
      the GC levels of the long sequences in which they are located. (vii) The CpG
      levels of both Alus and CpG islands increase with their GC levels.

PMID- 9931466
TI  - Genomic structure and chromosomal mapping of the human and mouse hippocalcin
      genes.
AB  - In an attempt to elucidate the possible relationship of hippocalcin to
      neurological disorders, we isolated and analyzed the human and mouse hippocalcin
      genes. The human and mouse hippocalcin genes contain three exons and two introns,
      and span approximately 7 and 8kb, respectively. The exon/intron splice junctions
      of the human and mouse genes are all situated in exactly the same position and
      are not consistently placed with respect to the coding regions of the tandemly
      repeated EF-hand motifs. The amino acid sequences of human and mouse hippocalcins
      deduced from the genes are 100% identical. Within the 2-kb 3'-flanking sequences
      of the human and mouse genes, one conserved polyadenylation signal was identified
      at positions 762 and 823bp downstream from TAG, respectively. Within the 2.6-kb
      5'-flanking sequences of the human and mouse genes, neither a canonical 'TATA'
      box nor a 'CAAT' box was found. Southern blot analysis of the human and mouse
      genomic DNAs demonstrated that the positive bands coincide exactly with those
      expected from the sequence of the cloned genes, indicating that the human and
      mouse hippocalcin genes are present as a single-copy gene. Fluorescence in-situ
      hybridization revealed that the human hippocalcin gene is located at chromosome 1
      p34.2-35 and the mouse hippocalcin gene at chromosome 4 D2-D3.

PMID- 9931468
TI  - Molecular characterization of cDNA for phospholipase A2-activating protein.
AB  - A phospholipase A2-activating protein (PLAP) cDNA was cloned and sequenced from a
      human monocyte cDNA library, and expressed as a histidine-tagged fusion protein.
      The DNA-deduced aa sequence of human PLAP was 80,826 Da; however, SDS-PAGE
      analysis revealed a 72-74 kDa protein which matched the size of native PLAP from
      human monocytes. Anti-sense plap oligonucleotide blocked cholera toxin-induced
      release of 3H-labeled arachidonic acid from cells, indicating a potential role
      for PLAP in regulating phospholipase A2 activity.

PMID- 9931469
TI  - Eimeria tenella: cloning and characterization of cDNA encoding a S3a ribosomal
      protein.
AB  - A lambda Zap II cDNA library was constructed from Eimeria tenella first-
      generation schizonts mRNA and screened with a mouse serum raised against this
      parasitic stage. This serum identified a clone encoding a S3a ribosomal protein
      (EtS3a). The 858-bp cDNA fragment, containing the entire parasitic gene encoded a
      highly basic protein of 264 amino acids (aa) with a molecular weight of
      29.780kDa. Based upon amino acid sequence comparison, EtS3a is highly homologous
      to v-fos transformation effector (encoded by the fte-1 gene) and cyc-07 (a plant
      homologue of fte-1) and similar to the yeast MFT1 (encoded by the mitochondrial
      fusion targeting gene). The expressions of mammalian fte-1, plant cyc-07 and
      yeast MFT1 have all been shown to be cell-cycle-regulated and involved in protein
      synthesis at the level of the ribosome. Since EtS3a expression is also
      developmentally regulated, we suggest that this gene product is a functional
      homologue of fte-1, cyc-07 and MFT1 and an important molecule regulating the
      development of Eimeria tenella.

PMID- 9931470
TI  - cDNA cloning and expression of Bacillus thuringiensis Cry1Aa toxin binding 120
      kDa aminopeptidase N from Bombyx mori.
AB  - Bacillus thuringiensis Cry1Aa toxin binds to a 120 kDa putative receptor protein
      in the Bombyx mori midgut. Recently, this protein was purified and identified as
      glycosyl-phosphatidylinositol (GPI) anchored aminopeptidase N (APN). In this
      study, a full-length cDNA thought to encode this 120 kDa APN was isolated and
      sequenced. It has a 2958 bp ORF encoding 986 amino acids. In the deduced amino
      acid sequence, we identified GPI-anchor and zinc-metallopeptidase signals, which
      are the same as those of APNs of other insects that are reported to be putative
      Cry1 toxin receptors. The B. mori APN amino acid sequence also has a high
      similarity with those of the other APNs. Subsequently, the recombinant APN was
      expressed by Escherichia coli and its Cry1Aa toxin binding ability was analyzed.
      Ligand blotting showed that Cry1Aa toxin bound to the recombinant APN.

PMID- 9931471
TI  - Expression of the flgFG operon of Campylobacter jejuni in Escherichia coli yields
      an extra fusion protein.
AB  - Two Campylobacter jejuni genes with homology to the Escherichia coli flgF and
      flgG genes encoding two of the basal body rod proteins were isolated, and the
      nucleotide sequence was determined and analyzed. These two C. jejuni genes were
      shown, by Northern hybridization analysis, to function as a single operon
      (flgFG). Two transcriptional start sites were detected upstream of flgF,
      corresponding to the two RNA transcripts detected in the Northern blot. Western
      blot immunoassays using anti-FlgF and anti-FlgG antibodies demonstrated the
      synthesis of FlgF and FlgG proteins in C. jejuni and in Escherichia coli
      containing the C. jejuni flgF and flgG genes. Maxicell analysis and Western
      immunoblots using anti-FlgF antibodies to probe flgFG-encoded proteins in E. coli
      revealed the presence of a protein with a molecular mass of approximately the
      combined mass of the FlgF and FlgG proteins. Anti-FlgF antibodies detected in C.
      jejuni cell extracts the native FlgF protein and also a higher-molecular-weight
      protein that is likely encoded by the flgF and part of the flgG sequences.

PMID- 9931472
TI  - Molecular cloning, expression and localization of human 105 kDa heat shock
      protein, hsp105.
AB  - We have shown that the 105 kDa heat shock protein (hsp105alpha) and hsp105beta
      (42 degreesC-specific heat shock protein) constitute high molecular mass (HMM)
      heat shock proteins (HSPs) in mouse cells. However, since HMM HSPs have not been
      identified in human cells, we screened a cDNA library constructed with poly(A)+
      RNA derived from heat-shocked human HeLa cells using mouse hsp105alpha cDNA. Two
      full-length cDNA clones were obtained: the pBH105-1 insert encoded an 858-amino
      acid protein, and the pBH105-2 insert encoded an 814-amino-acid protein which
      lacked 44 amino acids from pBH105-1. The deduced amino acid sequences of pBH105-1
      and pBH105-2 inserts were highly homologous to mouse hsp105alpha (96%) and
      hamster hsp110 (92%), and to mouse hsp105beta (93%), respectively. The transcript
      of pBH105-1 was induced by various stresses in HeLa cells, but the transcript of
      pBH105-2 was only induced during heat shock at 42 degreesC. These results
      indicated that pBH105-1 and pBH105-2 encoded human hsp105alpha and hsp105beta,
      respectively. Furthermore, a rabbit antibody was raised against recombinant human
      hsp105alpha, and immunofluorescence study also confirmed that hsp105 was present
      in the cytoplasm but was not found in the nucleoli of mammalian cells under both
      nonstressed and stressed conditions.

PMID- 9931473
TI  - Multiple p450alk (cytochrome P450 alkane hydroxylase) genes from the halotolerant
      yeast Debaryomyces hansenii.
AB  - The halotolerant alkane-assimilating yeast Debaryomyces hansenii was examined for
      P450 alkane hydroxylase genes known to be required for alkane assimilation in
      Candida. Four distinct P450alk gene segments and an allelic segment were isolated
      using PCR based on degenerate primers derived from the CYP52 family of alkane
      inducible P450 genes. A screen of a genomic library (15-20kb inserts) constructed
      for this study, using a probe based on the PCR-isolated segments, yielded seven
      clones. This has led to the isolation and sequence of two full-length genes DH
      ALK1 and DH-ALK2. These genes, each with an ORF of 1557 bp (519 aa), contained no
      apparent introns and showed 64% nucleotide sequence homology (61% based on the
      deduced amino acid sequences). The deduced proteins had predicted molecular
      weights of 59,254Da (DH-ALK1) and 59,614Da (DH-ALK2) and have been designated
      CYP52A12 and CYP52A13 by the P450 Nomenclature Committee. Phylogenetic analysis
      based on Neighbor Joining Tree showed that DH-ALK1 and DH-ALK2 constitute new
      genes located on two distinct branches and are most related to the gene CYP52A3
      (60% deduced aa homology) and are least related to the gene CYP52C2 (41% deduced
      aa homology), both of C. maltosa. The isolated genes will provide tools to better
      understand the diversity of the P450alk family in eukaryotic microorganisms
      adapted to varied environmental conditions.

PMID- 9931474
TI  - Mycobacteriophage D29 integrase-mediated recombination: specificity of
      mycobacteriophage integration.
AB  - Mycobacteriophage D29 is a lytic phage that infects both fast- and slow-growing
      species of the mycobacteria. D29 forms clear plaques on lawns of Mycobacterium
      smegmatis and Mycobacterium bovis bacille Calmette-Guerin (BCG) in which a very
      high proportion of infected cells are killed. However, genomic analysis of D29
      demonstrates that it is a close relative of the temperate mycobacteriophage L5,
      and is presumably a non-temperate derivative of a temperate parent. The D29
      genome encodes a putative integrase protein with a primary amino acid sequence
      similar to that of the L5 integrase; the corresponding int genes fall in colinear
      positions within the D29 and L5 genomes, immediately flanking and transcribed
      away from their associated attP sites. We show here that the D29 integrase is
      functional and catalyzes integrative recombination between the D29 attP site and
      the M. smegmatis attB site in vitro in an mIHF-dependent manner. D29 integrase
      also mediates recombination between the L5 attP site and attB DNA and,
      reciprocally, L5 integrase catalyzes recombination with D29 attP DNA. However, in
      both in-vitro and in-vivo assays, the D29-encoded integrase recombines the D29
      attP more efficiently than the L5 attP, and vice versa, suggesting that each
      integration system has evolved a degree of specificity of attP recognition. We
      also present the sequences of the putative attP site and integrase protein of the
      cryptic prophage-like element phiRv2, and compare them to those of
      mycobacteriophages L5 and D29.

PMID- 9931475
TI  - Structure, expression profile and chromosomal location of an isolog of DNA-PKcs
      interacting protein (KIP) gene.
AB  - A novel DNA-PKcs interacting protein, KIP (kinase interacting protein), was
      recently isolated using a two-hybrid analysis which showed a significant homology
      to calcineurin B. We found other ESTs showing significant similarity to KIP gene
      in the dbEST database and isolated a cDNA clone which encodes a 187 amino acid
      polypeptide from a human fetal brain cDNA library. This protein (termed KIP2 for
      kinase interacting protein 2) has sequence homology to KIP (46% identical and 64%
      similarity). RT-PCR analysis showed that the messenger RNA was ubiquitously
      expressed in various human tissues. Based on PCR-based analysis with a radiation
      hybrid cell panel and fluorescence in situ hybridization, the gene was localized
      to the q24 region of chromosome 15.

PMID- 9931476
TI  - Molecular characterization of a novel beta-1,3-exoglucanase related to
      mycoparasitism of Trichoderma harzianum.
AB  - Trichoderma harzianum, a soil-borne filamentous fungus, is capable of
      parasitizing several plant pathogenic fungi. Secretion of lytic enzymes, mainly
      glucanases and chitinases, is considered the most crucial step of the
      mycoparasitic process. The lytic enzymes degrade the cell walls of the pathogenic
      fungi, enabling Trichoderma to utilize both their cell walls and cellular
      contents for nutrition. We have purified a 110kDa novel extracellular beta-1,3
      exoglucanase from T. harzianum, grown with laminarin or in dual cultures with
      host fungi. The corresponding gene, lam1.3, and its cDNA were isolated and their
      nucleotide sequences determined. The deduced amino-acid sequence predicted a
      molecular mass of 110.7kDa of a mature protein excluding a signal peptide. LAM1.3
      showed high homology to EXG1, a beta-1,3-exoglucanase of the phytopathogenic
      fungus Cochliobolus carbonum, and a lower homology to BGN13.1, a beta-1,3
      endoglucanase isolated from T. harzianum. However, it contains a unique C
      terminal embodying cysteine motifs. The expression of lam1.3 in growth with
      laminarin, but not with glucose, was found to be a result of differential
      accumulation of the corresponding mRNA.

PMID- 9931477
TI  - Structure and expression of a novel human FGF, FGF-19, expressed in the fetal
      brain.

PMID- 9931478
TI  - Differential regulation of angiotensinogen and AT1A receptor mRNA within the rat
      subfornical organ during dehydration.
AB  - The present study describes the differential rostro-caudal patterning of
      angiotensinogen (AoGen) and AT1A receptor mRNAs in the rat SFO using specific and
      validated oligodeoxynucleotide probes for in situ hybridization. Highest levels
      of AoGen-specific gene expression were observed in the rostral region of the SFO
      with gradually decreasing intensity towards the caudal region of this sensory
      circumventricular organ lacking blood-brain barrier function. AoGen-related
      hybridization signals proved to be specifically prominent above cells in lateral
      aspects of the SFO, surrounding septal venules. Maximal expression of the AT1A
      receptor-specific gene, on the other hand, could be detected in the neuron
      enriched, ventro-medial core region and dorsal annulus of the SFO, with low
      intensity hybridization signals in its rostral and caudal parts. Water
      deprivation for 48 h, leading to extracellular hypertonic hypovolemia with
      elevated circulating AngII concentrations within the physiological range, caused
      a significant increase in AoGen-specific hybridization signals in the rostral and
      medial SFO regions. AT1A receptor gene expression and AngII receptor binding were
      markedly stimulated in the medial and caudal regions of the SFO (core and
      annulus) as compared to euhydrated animals. These data indicate, that mild
      dehydration differentially up-regulates AoGen- and AT1A receptor-specific mRNA
      formation as well as AT1 receptor binding in distinct regions of the SFO, and
      supports the involvement of different cellular subgroups in the expression of two
      major components of the central nervous renin-angiotensin system in this sensory
      circumventricular organ.

PMID- 9931479
TI  - DNA unwinding in the CYC1 and DED1 yeast promoters.
AB  - The capacity of promoter DNA of two yeast genes to be unwound was studied. Both
      promoters, those of the CYC1 and DED1 genes, contain long
      oligopurine.oligopyrimidine (R.Y) tracts. The two promoters were cloned into
      negatively supercoiled plasmids, and their sensitivity to single-strand specific
      nuclease P1 was examined. Extensive P1 cleavage was located within the R.Y
      tracts, and cleavage sites were mapped. The extent of cleavage was only slightly
      dependent on P1 concentration, indicating a slow conversion of an intermediate
      form of DNA into the P1 reactive state. The cleavage required negative
      supercoiling and was suppressed by NaCl, MgCl2 and spermine. Two-dimensional
      topoisomer analysis showed that six superhelical turns were opened in the
      plasmids examined. The results indicate that at sufficient torsional stress, the
      R.Y tracts can intermittently undergo a transition into an unwound, ready-to
      separate state. The oligopurine.oligopyrimidine tracts may thus serve as DNA
      unwinding centers in the gene promoters where they reside.

PMID- 9931480
TI  - Characterization of cDNAs encoding cytoplasmic ribosomal protein L15 and L27a in
      petunia (Petunia hybrida): primary structures and coordinate expression.
AB  - We have isolated two cDNA clones, PhRL15 and PhRL27a, encoding cytoplasmic
      ribosomal proteins L15 and L27a, from a cDNA library prepared from petunia petal
      protoplast cultures. An expressed sequence tag (EST) strategy was employed.
      PhRL15 and PhRL27a contained open reading frames corresponding to proteins of 204
      and 150 amino acids and molecular weights of 24,100 and 17,000Da, respectively.
      The deduced amino acid sequences of these clones are about 60% to 70%, identical
      with those of yeast and rat. Southern blot analysis indicates that each gene may
      be encoded by a small multigene. The transcription levels of both clones were
      high in young vegetative organs, at the early event of floral development, and in
      dividing petal protoplast, and relatively low in highly differentiated
      reproductive organs. Our results demonstrate that the expression levels of both
      clones are correlated with the rate of growth and coordinatively controlled in
      petunia plant.

PMID- 9931482
TI  - Sequence, expression and genetic mapping of a rainbow trout retinoblastoma cDNA.
AB  - A full-length cDNA for retinoblastoma (RB1) has been cloned from a cDNA library
      prepared from 3-week-old rainbow trout (Oncorhynchus mykiss) eyed embryos. The
      trout RB1 cDNA encodes a predicted protein of 910 amino acids and is the most
      divergent cloned retinoblastoma gene sequence to date. RT-PCR studies reveal high
      levels of RB1 expression by the second week of embryogenesis, which remains
      uniformly expressed until hatching. Expression studies of adult fish tissues show
      the RB1 gene to be expressed in all tissues examined, including the oesophagus,
      eye, liver, intestine, posterior and anterior kidney, skin, stomach, muscle,
      spleen, gill, swim bladder, gonads and brain. The RB1 gene appears to be a single
      copy gene based on Southern analysis, and maps to linkage group XVI in the trout
      genome map. Polymorphisms in the RB1 gene and in closely linked markers should
      facilitate LOH analysis of RB1.

PMID- 9931481
TI  - Both neuronal NO synthase and nitric oxide are required for PC12 cell
      differentiation: a cGMP independent pathway.
AB  - PC12 cells are used as a model system to study neuronal differentiation. Nerve
      growth factor (NGF) triggers a differentiation pathway in PC12 cells. Neurite
      outgrowth (a morphological marker of differentiation) in PC12 cells is
      significantly reduced in the presence of the NOS inhibitor l-NAME, but not d
      NAME, implicating NOS in the differentiation process. Previously we have shown
      that the neuronal NO synthase (nNOS) isoform is induced in PC12 cells in the
      presence of NGF. Thus, we wished to further evaluate the role of nNOS and NO in
      PC12 cell differentiation. When a dominant negative mutant nNOS expression vector
      was transiently transfected into NGF-treated PC12 cells, it significantly reduced
      PC12 cell neurite outgrowth. Thus, we concluded that the NO required for PC12
      cell differentiation, in response to NGF, is produced by nNOS. NO alone was
      insufficient to induce differentiation as cells treated with the NO donor, sodium
      nitroprusside did not produce neurites. Treatment of PC12 cells with
      oxyhemoglobin (an NO scavenger) was also found to significantly reduce the number
      of neurites produced by PC12 cells treated with NGF. Thus, NO appears to be
      necessary, but not sufficient, to induce differentiation, and its mode of action
      appears to be extracellular. A well documented action of NO is to activate
      soluble guanylate cyclase. Thus, we determined the role of soluble guanylate
      cyclase activation as a means by which NO induces PC12 cell differentiation.
      However, in the presence of NGF (to prime PC12 cells for differentiation) and l
      NAME (to specifically remove the NO component), 8Br-cGMP (a cGMP analog) failed
      to induce PC12 cell differentiation. In addition, blockade of sGC activity with
      specific inhibitors failed to block NGF-induced PC12 cell differentiation. We
      conclude that the NO required for PC12 cell differentiation is produced by nNOS
      and that the NO exerts its effects on surrounding PC12 cells in a sGC/cGMP
      independent manner.

PMID- 9931483
TI  - Localization of mRNAs for synaptojanin isoforms in the brain of developing and
      mature rats.
AB  - The localization of mRNAs for synaptojanin 1 and 2, inositol 5-phosphatases, in
      the brain was examined by in situ hybridization histochemistry. Synaptojanin 1
      mRNA was detected in almost all neurons of the central nervous system throughout
      developing and mature stages, although its splicing variant (synaptojanin 1-p145
      I) mRNA was expressed dominantly in forebrain and cerebellar cortex. Synaptojanin
      2 mRNA was first detected in neurons of the olfactory bulb, the cerebral cortex,
      the hippocampus, and the cerebellar cortex on early postnatal days. As the
      postnatal development proceeded, the expression signal was evident in the white
      matters, presumptive oligodendrocytes, with the clear expression remaining in
      neurons of the olfactory tubercle, hippocampal pyramidal cells and cerebellar
      Purkinje cells.

PMID- 9931484
TI  - Genomic organization of the genes encoding dihydroflavonol 4-reductase for flower
      pigmentation in the Japanese and common morning glories.
AB  - Genomic DNA segments (approximately 17kb) containing three DFR genes in the
      Japanese and common morning glories were sequenced. The three DFR genes in both
      plants were found to be arranged in a tandem array, and all of them comprised six
      exons with identical intron positions. Their DFR-B genes carrying longer introns
      than the DFR-A and DFR-C genes were expressed extensively in the young buds of
      pigmented flowers, and the transcription starting site for the DFR-B mRNA of the
      Japanese morning glory was determined. The DFR-B gene of the common morning glory
      was expressed considerably in stems, moderately in sepals and leaves, whereas the
      DFR-A and DFR-C genes of the same plant were expressed scarcely but significantly
      in the young flower buds and stems. Several novel mobile element-like sequences
      of around 200bp were found in the genomic DFR regions. A phylogenetic tree
      indicated that each DFR gene in the Japanese morning glory is most closely
      related to the corresponding DFR gene in the common morning glory, and that the
      DFR-B gene is the most diversified gene among the three DFR genes. These
      structural and functional features of the DFR genes and their evolutionary
      implications are discussed.

PMID- 9931485
TI  - Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve
      injury.
AB  - Neurotrophins have specificity toward distinct subpopulations of dorsal root
      ganglion (DRG) neurons with different neurotrophin receptors. It has been
      suggested that neurotrophins also play important roles in mature DRG neurons
      after injury. In the present study, we examined the expression of nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3)
      mRNAs in the DRG after a peripheral nerve injury. The data showed that following
      a spinal nerve ligation, the level of NGF mRNA increased 4 times over the normal
      level and was maintained at a high level for a period of 3 weeks. The induction
      of BDNF mRNA was brief (lasting less than 3 days) and lesser in quantity (
      approximately 1. 7 times increase) compared to NGF expression. The expression of
      NT-3 mRNA was not detected either in normal or nerve injured rats. Results
      suggest that different neurotrophins play different functional roles in the DRG
      after spinal nerve injury.

PMID- 9931486
TI  - Cloning and sequence analysis of two catechol-degrading gene clusters from the
      aniline-assimilating bacterium Frateuria species ANA-18.
AB  - The aniline-assimilating bacterium Frateuria species ANA-18 produced two catechol
      1,2-dioxygenases, CD I and CD II, and two muconate cycloisomerases, MC I and MC
      II. The catA genes catA1 and catA2 encoding CD I and CD II, respectively, were
      cloned from a gene library of this bacterium. The catA1 gene was clustered with
      catB1 encoding MC I, catC1 encoding muconolactone isomerase (MI), catD encoding
      beta-ketoadipate enol-lactone hydrolase (ELH), and ORFR1 encoding a putative LysR
      type regulator. The organization of these genes was ORFR1catB1C1D. The catA2 gene
      also constructed a gene cluster involving catB2 encoding MC II, catC2 encoding
      MI, and ORFR2 encoding a putative LysR-type regulator with the alignment of
      ORFR2catB2A2C2. The intergenic regions of ORFR1-catB1 and ORFR2-catB2 contained
      homologous sequences with the catR-catB intergenic region containing a repression
      binding site and activation binding site of CatR in Pseudomonas putida. These
      findings suggest that the two cat clusters were regulated independently in their
      expression. When a product of cloned catD was added to a reaction mixture
      containing beta-ketoadipate enol-lactone, beta-ketoadipate was produced. This
      observation showed that the cloned catD encoded ELH and was expressed in
      Escherichia coli. We found that Frateuria sp. ANA-18 had a large plasmid with a
      molecular size more than 100kb. Polymerase chain reaction amplifying partial catA
      genes and Southern hybridization analyses with probes containing catA genes were
      conducted, to examine the localization of the two catA genes. We concluded that
      the catA1 and catA2 genes were located on the chromosomal and large plasmid DNAs,
      respectively, in Frateuria sp. ANA-18.

PMID- 9931487
TI  - Identification and cloning of three novel human G protein-coupled receptor genes
      GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain.
AB  - The G protein-coupled receptor (GPCR) family share a structural motif of seven
      transmembrane segments with large numbers of conserved residues in those regions.
      Here, we report the identification and cloning of two novel human intronless GPCR
      genes, GPR52, GPR55 and a pseudogene PsiGPR53. GPR55 was identified from the
      expressed sequence tags (EST) database whereas GPR52 and pseudogene PsiGPR53
      originated from the high throughput genome (HTG) database. A partial cDNA clone
      obtained from the IMAGE Consortium of GPR55 was used to screen a human genomic
      library to acquire the full length gene. GPR52 and PsiGPR53 were amplified from
      human genomic DNA using primers based on the HTG sequences. GPR55 and GPR52
      encode receptors of 319 and 361 amino acids, respectively. GPR55 gene was mapped
      to chromosome 2q37, using fluorescence in situ hybridization (FISH), and its mRNA
      transcripts have been detected in the caudate nucleus and putamen, but not in
      five other brain regions. Human receptors showing the highest amino acid identity
      to GPR55 include P2Y5 (29%), GPR23 (30%), GPR35 (27%) and CCR4 (23%). GPR52 gene
      localized to chromosome 1q24 shares the highest identity with GPR21 (71%),
      histamine H2 (27%) and 5-HT4 (26%) human receptors. PsiGPR53 is a pseudogene
      mapped to chromosome 6p21 that demonstrates the highest similarity to the MRG
      (35%), MAS (28%) and C5a (24%) human receptor genes.

PMID- 9931488
TI  - The leukemic oncogene tal-2 is expressed in the developing mouse brain.
AB  - tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a
      family of basic helix-loop-helix transcription factors and were originally
      isolated from the breakpoints of chromosomal translocations in human T-cell
      leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also
      in several endothelial structures and the central nervous system during
      development. On the other hand, the detailed function and the sites of expression
      of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic
      cDNA library and examined its expression pattern in the mouse, comparing with
      that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at
      embryonic day 12.5 in the following regions; 1) the diencephalon-the zona
      limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and
      the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the
      anterior pons. In the diencephalon and the mesencephalon, the expression sites of
      tal-2 gene were similar to those of tal-1, and its expression was stronger than
      that of tal-1. In the metencephalon, tal-2 expression was observed in the
      anterior pons, whereas tal-1 transcripts were detected in the entire pons, and
      showed stronger expression than tal-2. The tal-2 messages were barely detectable
      in the brain at birth. These results suggest that tal-1 and tal-2 are involved in
      the development of specific areas of the central nervous system.

PMID- 9931489
TI  - Effect of CpG methylation on expression of the mouse imprinted gene Mest.
AB  - We previously reported isolation of the mouse gene, Mest (mesoderm-specific
      transcripts), which is mapped to the proximal part of chromosome 6 and
      predominantly expressed in the mesoderm and its derivatives during development.
      Peg1, a paternally expressed gene isolated by a systematic screening of imprinted
      genes, was recently demonstrated to be identical to Mest. We and others have
      shown that the human homolog (MEST) of Mest is also imprinted so as to be
      expressed from the paternal copy and maps to 7q32. To study transcriptional
      regulation of Mest/Peg1, we examined the effect of DNA methylation on its
      expression. In the embryonal carcinoma (EC) cell line, MC12, from which Mest was
      originally isolated, the 5'-region harboring presumptive promoter of the gene was
      undermethylated. On the other hand, C4XX, a subclone of MC12 which had lost
      expression of Mest, was characterized by extremely high levels of methylation in
      the 5'-region, demethylation of which resulted in activation of Mest.
      Furthermore, a methylated reporter construct with the luciferase gene under the
      control of the putative promoter region of Mest was not competent to produce
      luciferase activity in MC12 cells. These results suggest a suppressive role for
      DNA methylation in Mest expression. However, neither methylated nor unmethylated
      reporter constructs showed luciferase activity in a primary culture from the
      adult kidney, in which Mest is down-regulated despite apparent unmethylation of
      the paternal allele. Taken together, the data suggest that there are probably two
      modes of regulation for the Mest gene; one being a methylation-dependent
      mechanism that regulates imprinted expression of Mest during development, and the
      other being a methylation-independent mechanism that is involved in down
      regulation of Mest in adult tissues.

PMID- 9931490
TI  - XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase
      family, is preferentially expressed in the CNS.
AB  - In the present study, we have isolated a cDNA encoding a novel member of the
      family of zinc metallopeptidases that includes neutral endopeptidase and
      endothelin-converting enzyme. The predicted amino-acid sequence of this enzyme,
      termed XCE, consists of 775 amino-acids with a single putative membrane-spanning
      region, an N-terminal cytoplasmic domain of 59 residues, and a large luminal
      domain that contains a characteristic zinc-binding motif. Western blot analysis
      of cells stably expressing this new metallopeptidase revealed a glycosylated
      protein of approximately 95 kDa. XCE mRNA was found to be predominantly expressed
      in the central nervous system, sympathetic ganglia and in uterine subepithelial
      cells. In the rat and human CNS, a very specific pattern of neuronal labelling
      (in presumptive cholinergic interneurons of basal ganglia, basal forebrain
      neurons, as well as brainstem and spinal cord motoneurons) was detected by in
      situ hybridization histochemistry. The enzyme substrate, as yet unidentified,
      might be found among the numerous neuropeptide transmitters which are colocalized
      with acetylcholine in these neurons.

PMID- 9931491
TI  - Structures, sequence characteristics, and synteny relationships of the
      transcription factor E4TF1, the splicing factor U2AF35 and the cystathionine beta
      synthetase genes from Fugu rubripes.
AB  - A cosmid containing the beta-amyloid precursor protein (APP) from Fugu rubripes
      has been completely sequenced. In addition to APP, the cosmid contains the E4TF1
      60 transcription factor, the U2AF35 pre-mRNA splicing factor, and the
      cystathionine beta synthetase (CBS) gene. The human homologues of all four genes
      map to human chromosome 21 but are not clustered; APP and E4TF1-60 map within
      21q21, whereas U2AF35 and CBS map approximately 20Mb distal in 21q22. 3. The
      protein sequences of the Fugu genes vary in their overall level of similarity to
      their mammalian homologues, but several regions of functional importance are
      almost identical. As expected, the intron/exon structures of the homologous pairs
      of genes are highly conserved, but there are significant differences in the
      compaction ratios. The introns of APP and E4TF1-60 are 49- and 24-fold smaller in
      Fugu than in human, and the intergenic distance is compressed at least 100-fold.
      For U2AF35 and CBS, the introns are compressed only five- to eightfold. These
      size differences were compared with those for a number of previously reported
      Fugu genes; in general, levels of compaction of Fugu genes are consistent with
      the isochore locations of the human homologues.

PMID- 9931492
TI  - Isoform-specific translocation of protein kinase C following glutamate
      administration in primary hippocampal neurons.
AB  - High concentrations of glutamate, the major excitatory neurotransmitter in the
      mammalian brain, lead to intracellular calcium overload resulting in excitotoxic
      damage and death of neurons. Since protein kinase C (PKC) is involved in neuronal
      degeneration resulting from cerebral ischemia and from glutamate excitotoxicity,
      we investigated the effect of glutamate on changes in the cellular distribution
      of various PKC isoforms in cultured hippocampal neurons in comparison with the
      effects elicited by the PKC activator phorbol ester. Out of the expressed PKC
      isoforms alpha, gamma, epsilon, zeta and lambda only the conventional isoforms
      PKC alpha and gamma responded to glutamate. Using subcellular fractionation and
      Western blotting with isoform-specific antibodies and immunocytochemical
      localization with confocal laser scanning microscopy, we observed that phorbol
      ester and glutamate have different effects on PKC isoform redistribution: Whereas
      phorbol ester resulted in translocation of PKC alpha and PKC gamma toward a
      membrane fraction, the glutamate-mediated rise in intracellular calcium
      concentration induced a translocation mainly toward a detergent-insoluble,
      cytoskeletal fraction. Immunocytochemical analysis revealed an isoform-specific
      translocation following glutamate treatment: PKC gamma was translocated mainly to
      cytoplasmic, organelle-like structures, whereas PKC alpha redistributed to the
      plasma membrane and into the cell nucleus. The latter result is of special
      interest, as it indicates that nuclear PKC may play a role in processes of
      excitotoxic cell damage.

PMID- 9931493
TI  - Structure and chromosome localization of the human CASP8 gene.
AB  - The human CASP8 gene, whose product is also known as caspase 8 and FLICE, encodes
      an interleukin-1beta converting enzyme (ICE)-related cysteine protease that is
      activated by the engagement of several different death receptors. Caspase 8 is
      immediately recruited to the Fas receptor once it oligomerizes, and its protease
      activity is crucial for the apoptotic response generated by the resulting death
      inducing signaling complex (DISC). We report here that the CASP8 gene contains at
      least 11 exons spanning approximately 30kb on human chromosome band 2q33-34. This
      region of human chromosome 2 was previously reported as the location of the
      CASP10 gene, whose product is closely related to caspase 8. Chromosome 2 band q33
      34 is also involved in tumorigenesis, with loss of heterogeneity (LOH) being
      reported in a number of tumors. We also report EcoRI and HindIII polymorphisms
      that may prove to be useful in disease analysis. Both caspases 8 and 10 contain
      long pro-domains with duplicated death effector domains (DEDs), as well as their
      corresponding cysteine protease catalytic domains. Thus, it appears that CASP8
      and CASP10 have evolved by tandem gene duplication, much like the CASP1, CASP4
      and CASP5 gene cluster on human chromosome 11q22.2-22.3.

PMID- 9931494
TI  - Isolation and confirmation of function of the Coccidioides immitis URA5 (orotate
      phosphoribosyl transferase) gene.
AB  - The OPRTase (URA5) gene of the human pathogenic fungus, Coccidioides immitis
      (Ci), was cloned, sequenced, chromosome-mapped and expressed both by
      transformation of Escherichia coli and by complementation of wdura5Delta, an
      auxotrophic strain of Wangiella dermatitidis (Wd) with a disrupted URA5 gene. A
      functional assay of the recombinant URA5 expressed by E. coli was conducted to
      ensure that the isolated Ci gene encodes the appropriate enzyme. In the absence
      of a transformation system for Ci, we also used a reported method of introduction
      of heterologous DNA into cells of the phylogenetically related fungus, Wangiella
      dermatitidis, to confirm the function of the Ci URA5 gene. Both the genomic and
      cDNA sequences of the Ci URA5 gene are presented. The transcription start point
      and two poly(A) addition sites were confirmed. The gene contains a 714-bp ORF
      that translates a 238-amino-acid (aa) protein of 25.5kDa and pI of 6.5. No
      introns are present. The translated protein contains a single, putative N
      glycosylation site. The deduced Ci protein showed 55-63% aa sequence similarity
      to reported fungal OPRTases. The URA5 gene was mapped to chromosome IV of Ci, and
      was shown to be a single copy gene by Southern and Northern hybridizations.
      Transformation of the wdura5Delta mutant to prototrophy was accomplished by
      electroporation of Wd yeast cells with the Ci URA5 gene. Cellular uptake of the
      heterologous DNA was confirmed by Southern hybridization. The stable
      transformants were unable to grow on a medium containing 5-FOA. Expression of the
      Ci URA5 gene can be used as a selectable marker for a transformation system, and
      the latter is essential for molecular studies of this pathogenic fungus.

PMID- 9931495
TI  - Redistribution of F-actin and large dense-cored vesicles in the human
      neuroblastoma SH-SY5Y in response to secretagogues and protein kinase Calpha
      activation.
AB  - Our previous studies have shown that noradrenaline release is enhanced by
      activation of protein kinase Calpha in SH-SY5Y cells. In the present study, we
      report that activation of protein kinase Calpha leads to (a) partial
      redistribution of the F-actin cytoskeleton and (b) a 2.5-fold increase in the
      number of large dense-cored vesicles within 100 nm of the plasma membrane. This
      redistribution can be prevented by down-regulation of protein kinase Calpha by up
      to 48 h exposure to phorbol dibutyrate. Treatment with the secretagogues 100 mM
      KCl, the Ca2+ ionophore A23187 (20 microM) and 1 mM carbachol also leads to a
      partial disassembly of the F-actin cytoskeleton. This is accompanied by an
      increase in the number of large dense cored vesicles at the plasma membrane
      following exposure to KCl and A23187 but not following exposure to carbachol.
      These results are discussed in relation to the hypothesis that a key step in the
      enhancement of noradrenaline release following activation of protein kinase
      Calpha and elevation of intracellular calcium is the movement of large dense
      cored vesicles to the plasma membrane following partial disassembly of the F
      actin cytoskeleton.

PMID- 9931496
TI  - Integrational plasmids for the tetracycline-regulated expression of genes in
      Streptococcus pneumoniae.
AB  - Plasmids for the tetracycline regulated gene expression in Streptococcus
      pneumoniae have been developed. The plasmids were used for the tetracycline
      dependent production of firefly luciferase in streptococci. The production of
      luciferase can be induced fivefold by the addition of tetracycline. By using two
      promoters of different strength and depending on the presence or absence of
      tetracycline, an 80-fold range of luciferase activities can be covered. The
      system was also used to construct strains that depend on the addition of
      tetracycline for the production of the A subunit of DNA gyrase, an essential
      streptococcal protein. The growth of such a strain depends on the addition of
      tetracycline to the medium. In the absence of tetracycline, the cells cease to
      grow and are not viable. The system presented in this report should be useful for
      the characterization of gene networks in S. pneumoniae. It especially allows one
      to study the function of essential genes that can not be investigated by standard
      knock-out techniques.

PMID- 9931497
TI  - Molecular cloning, functional characterization and possible cooperativity between
      the murine P2X4 and P2X4a receptors.
AB  - We have cloned and functionally characterised the mouse orthologue of the P2X4
      receptor, mP2X4, and a splice variant of this receptor, mP2X4a. mP2X4 is 388
      amino acids in length and shares 94% and 87% identity with the rat and human P2X4
      receptors, respectively, while mP2X4a is 361 amino acids in length and lacks a 27
      amino acid region in the extracellular domain corresponding to exon 6 of the
      known P2X receptor gene structures. When expressed in Xenopus laevis oocytes,
      mP2X4 produces a rapid inward current in response to ATP with an EC50 of 1.68+/
      0.2 microM, consistent with the affinity of the rat and human P2X4 receptors for
      ATP. This agonist response is potentiated by the P2X receptor antagonists
      suramin, Reactive blue 2 and, over a limited concentration range, by PPADS.
      Although mP2X4a forms a poorly functional homomeric receptor, it appears able to
      interact with the full-length mP2X4 subunit to result in a functional channel
      with a reduced affinity for ATP. These results suggest a possible role for splice
      variants of P2X receptors in the formation of functional heteromeric ion
      channels.

PMID- 9931498
TI  - Molecular cloning and characterization of the mouse Ecm1 gene and its 5'
      regulatory sequences.
AB  - The mouse Ecm1 (extracellular matrix protein 1) gene codes for an extracellular
      protein of 85kDa. We have determined the primary structure of this gene and
      analysed 1665 bases of its 5' upstream regulatory region. The gene is
      approximately 5kb long and contains 11 exons. The exons range in size from 45 to
      375bp, whereas the intron sizes ranges from 95 to 1115bp. All splice
      donor/acceptor sites conform to the GT/AG rule. The 5' upstream sequences contain
      a TATA-box, a CCAAT-box and an inverted CCAAT-box. We have analysed the Ecm1
      regulatory elements by reporter gene constructs and transient transfections in
      the stromal osteogenic cell line MN7. Progressive deletion of the Ecm1 promoter
      revealed the presence of a region with a repressive activity between -110 and 
      317 and showed that a 110-bp fragment, containing potential binding sites for
      AP1, Sp1, GATA and Ets family of transcription factors, is sufficient for CAT
      expression in MN7 cells. Except for the GATA binding site, these regulatory
      sequences are conserved in the human promoter. Point mutation analysis revealed
      that the AP1, Sp1 and Ets binding sites are absolutely necessary for Ecm1
      expression in MN7.

PMID- 9931499
TI  - Identification of a human 5-HT6 receptor variant produced by alternative
      splicing.
AB  - The complexity of the 5-hydroxytryptamine (5-HT) (serotonin) receptor family has
      been increased by the findings that isoforms or splice variants exist for
      subtypes such as the 5-HT2B, 5-HT2C, 5-HT4 and 5-HT7 subtypes. Further molecular
      biological studies in our laboratory have demonstrated that a splice variant of
      the 5-HT6 receptor exists in the human brain. Experiments performed using a
      degenerate PCR approach from human caudate cDNA revealed a 5-HT6 receptor clone
      with a 289 bp deletion of the region coding for transmembrane IV through the
      third intracellular loop. This deletion produces a frameshift creating a
      downstream stop codon which results in a truncated protein containing 10 unique
      amino acids at its carboxyl end. The variant transcript occurs as a result of
      alternative splicing using an upstream donor site and the acceptor site from the
      first intron in the 5-HT6 receptor gene. The splicing pattern seen for this
      transcript was not detected in rat or mouse whole brain cDNA by PCR due to the
      lack of a consensus 5' donor site. Coexpression of the variant 5-HT6 transcript
      and the full length 5-HT6 transcript was observed in caudate and substantia nigra
      but not in hippocampus, cortex, cerebellum and thalamus. Transient transfection
      of a 5-HT6 variant construct into Cos-7 cells demonstrated that a truncated
      receptor was translocated to the membrane but appeared nonfunctional.

PMID- 9931500
TI  - Isolation from genomic DNA of sequences binding specific regulatory proteins by
      the acceleration of protein electrophoretic mobility upon DNA binding.
AB  - We report an efficient and flexible in vitro method for the isolation of genomic
      DNA sequences that are the binding targets of a given DNA binding protein. This
      method takes advantage of the fact that binding of a protein to a DNA molecule
      generally increases the rate of migration of the protein in nondenaturing gel
      electrophoresis. By the use of a radioactively labeled DNA-binding protein and
      nonradioactive DNA coupled with PCR amplification from gel slices, we show that
      specific binding sites can be isolated from Escherichia coli genomic DNA. We have
      applied this method to isolate a binding site for FadR, a global regulator of
      fatty acid metabolism in E. coli. We have also isolated a second binding site for
      BirA, the biotin operon repressor/biotin ligase, from the E. coli genome that has
      a very low binding efficiency compared with the bio operator region.

PMID- 9931501
TI  - Fos expression during the critical period in visual cortex: differences between
      normal and dark reared cats.
AB  - The present study tested further the notion that immediate early gene expression
      is involved in neuronal plasticity during the critical period of visual cortex
      (VC) by comparing Fos induction in normal and dark reared (DR) cats. Western
      blots indicated that the level of induced Fos expression was higher in normal
      than DR cat VC at 5 weeks of age, comparable at 10 weeks, and higher in DR than
      normal cat VC at 20 weeks. Immunohistochemistry indicated that at 5 weeks Fos was
      induced in cells of all VC layers in both rearing conditions, but to a greater
      extent in normal than DR cats. At 20 weeks, Fos was largely restricted to cells
      above and below layer IV in both rearing conditions, but was induced to a greater
      extent in DR than normal cats. Thus, dark rearing appears to have very similar
      effects on Fos expression as it has on neuronal plasticity during the postnatal
      critical period.

PMID- 9931502
TI  - Molecular cloning and chromosomal mapping of mouse intronless myc gene acting as
      a potent apoptosis inducer.
AB  - Our previous findings suggest that the activation of the rat intronless myc gene
      provides a selective advantage in tumor suppression through apoptosis induction.
      In the present study, to examine whether intronless myc gene acting as an
      apoptosis inducer is evolutionarily conserved in mammalian cells, we isolated the
      mouse intronless myc gene and characterized it. A sequence analysis demonstrated
      that mouse intronless myc gene, ms-myc, has a linearly opened translatable frame
      consisting of 1293bp with 90% homology with that of rat s-myc. The chromosomal
      locus of ms-myc was identified on chromosome 19B by a fluorescent in situ
      hybridization (FISH) analysis. Gene transfection experiments showed that the
      transient overexpression of ms-Myc with transactivation activity effectively
      induces cell death in a wild-type p53-independent manner. In addition, cells
      stably expressing transfected ms-myc became more susceptible to apoptosis induced
      by genotoxic stress such as UV-irradiation and hydrogen peroxide compared with
      untransfected control cells. These observations suggest that the rodents commonly
      contain an s-myc-type of intronless myc gene with apoptosis-inducing activity.

PMID- 9931503
TI  - SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells,
      is a member of an epithelial membrane protein superfamily.
AB  - We have cloned a human cDNA, SEMP1 (senescence-associated epithelial membrane
      protein 1), using differential display (DD) of mRNA. We compared mRNA expression
      profiles between cultured normal senescent human mammary epithelial cells (HMECs)
      and proliferating, early passage HMECs. From the amino acid sequence of the open
      reading frame (ORF) of the cDNA, we infer that the protein belongs to a family of
      membrane-associated, epithelial cell-specific proteins. The translation product
      has 91% identity to a mouse protein, claudin-1, a tight junction (TJ)-associated
      protein. SEMP1 mRNA is expressed in human tissues, including adult and fetal
      liver, pancreas, placenta, adrenals, prostate and ovary but at low or
      undetectable levels in a number of human breast cancer cell lines. SEMP1 is a
      member of a superfamily of epithelial membrane proteins (EMPs), which may have
      multiple potential functions, including maintenance and regulation of cell
      polarity and permeability, perhaps through mechanisms involving tight junctions.

PMID- 9931504
TI  - A vector for promoter trapping in Bacillus cereus.
AB  - We constructed a promoter-trap plasmid, pAD123, for Bacillus cereus. This plasmid
      contains a promoterless gene that encodes a mutant version of the green
      fluorescent protein, GFPmut3a, that is optimized for fluorescence-activated cell
      sorting [Cormack, B.P., Valdivia, R.H., Falkow, S., 1996. FACS-optimized mutants
      of the green fluorescent protein (GFP). Gene 173, 33-38.]. The plasmid replicates
      and confers drug resistance in both Escherichia coli and B. cereus. We
      constructed a library in pAD123, which consists of 29000 clones containing
      chromosomal DNA from B. cereus strain UW85. A portion of the library (988 clones)
      was screened for GFP expression in B. cereus UW85 using a 96-well microtiter dish
      assay. GFP expression was detected by visual inspection with a fluorimager. We
      identified 21 clones as fluorescing in the initial screen, and further
      characterized these clones by restriction analysis, sequencing, and
      quantification of fluorescence intensity. Flow cytometry and cell sorting
      efficiently separated B. cereus cells expressing GFP from a 10000-fold excess of
      non-expressing cells. Selected clones provided useful markers to follow B. cereus
      populations on plant surfaces. Our results indicate that GFP and pAD123 are
      useful tools for identifying regulatory sequences in Bacillus cereus, and that
      flow cytometry and cell sorting is a useful method for screening large libraries
      constructed in this vector.

PMID- 9931505
TI  - Molecular cloning and characterization of porcine cDNA encoding a 90-kDa heat
      shock protein and its expression following hyperthermia.
AB  - We have isolated and sequenced cDNA clones encoding a 90-kDa heat shock protein
      (HSP90) from a porcine brain cDNA library. The sequence of the 2202-nucleotide
      coding region showed 88.6% homology with that of the human homologue. Moreover,
      the deduced amino acid sequence of the porcine hsp90 cDNA was 99.7% identical to
      that of the human counterpart, with a difference of only three amino acids in a
      total of 733 residues. Expression of the gene was greatly increased in cultured
      cells during recovery from heat shock treatment at 45 degrees C for 60 min. Three
      major transcripts 2.2, 3.0, and 4.1kb in size were detected by Northern blot
      hybridization. These transcripts were further identified in a whole-pig
      hyperthermia experiment. These three hsp90 transcripts were constitutively
      expressed in porcine tissues including kidney, liver, brain, and heart, and their
      levels were markedly enhanced during recovery from 30-min hyperthermia treatment
      at 43 degrees C. Furthermore, we found that HSP90 was preferentially expressed in
      pituitary gland, brain, adrenal gland, and testis, in comparison to the other
      tissues.

PMID- 9931506
TI  - Promoter-directed expression of recombinant fire-fly luciferase in the salivary
      glands of Hermes-transformed Aedes aegypti.
AB  - Molecular genetic analyses of biological properties characteristic of insect
      vectors of disease, such as hematophagy and competence for pathogens, require the
      ability to isolate and characterize genes involved in these processes. We have
      been working to develop molecular approaches for studying the promoter function
      of genes that are expressed specifically in the adult salivary glands of the
      yellow fever mosquito, Aedes aegypti. Genomic DNA fragments containing cis-acting
      promoter elements from the Maltase-like I (MalI) and Apyrase (Apy) genes were
      cloned so as to direct the expression of the reporter gene, luciferase (luc). The
      function of the promoters was assayed transiently in cultured insect cells and by
      germ-line transformation of Ae. aegypti. MalI and Apy DNA fragments consisting of
      at least 650 nucleotides (nt) of DNA immediately adjacent to the 5'-end of the
      initiation codon of the mosquito genes directed constitutive expression of the
      luc reporter gene in cultured cells. When introduced into Ae. aegypti
      chromosomes, approximately 1.5 kilobases (kb) of each promoter were able to
      direct the predicted developmental-, sex- and tissue-specific expression of the
      reporter gene in patterns identical to those determined for the respective
      endogenous genes.

PMID- 9931507
TI  - Genetic mechanisms for duplication and multiduplication of the human CYP2D6 gene
      and methods for detection of duplicated CYP2D6 genes.
AB  - The polymorphic CYP2D6 gene determines the rates at which several different
      classes of clinically important drugs are metabolized in vivo. A specific
      phenotype whereby a subject metabolizes drugs very rapidly (ultrarapid
      metabolizer, UM) has been shown to be caused by the presence of multiple active
      CYP2D6 genes on one allele. Hitherto, individuals with 1, 2, 3, 4, 5, or 13
      CYP2D6 genes in tandem have been described for various ethnic groups. In the
      present investigation, we present results from restriction mapping of the CYP2D
      loci of individuals with two or more consecutive CYP2D6 genes, along with
      sequence analysis of this gene (CYP2D6*2). Our results indicate that alleles with
      duplicated or multiduplicated genes have occurred through unequal crossover at a
      specific breakpoint in the 3'-flanking region of the CYP2D6*2B allele with a
      specific repetitive sequence. In contrast, alleles with 13 copies of the gene are
      proposed to have been formed by unequal segregation and extrachromosomal
      replication of the acentric DNA. We present a rapid and efficient PCR-based
      allele-specific method for the detection of duplicated, multiduplicated, or
      amplified CYP2D6 genes.

PMID- 9931508
TI  - Poly(ADP-ribose) polymerase interacts with novel Drosophila ribosomal proteins,
      L22 and l23a, with unique histone-like amino-terminal extensions.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that recognizes and binds
      to the nicks and ends of DNA, and catalyses successive ADP-ribosylation
      reactions. To clarify the function of PARP at the molecular level, we searched
      proteins which interact with PARP. In the auto-modification domain of PARP in
      Drosophila, there is a putative leucine-zipper motif which can interact with
      other protein molecules. To find interacting proteins we examined the auto
      modification domain of Drosophila PARP, using the Far-Western screening method.
      From six independent cDNA clones isolated, we characterized two clones, PBP-3 and
      PBP-12. The predicted amino acid sequences from 109 to 269 of PBP-3 and from 184
      to 312 of PBP-12 had more than 62% identities to mammalian L23a (rpl23a) and L22
      (rpl22), the ribosomal proteins of the large subunit. This indicated that PBP-3
      and PBP-12 are Drosophila homologues of L23a and L22, respectively. These
      Drosophila ribosomal protein L22 and L23a have additional Ala-, Lys- and Pro-rich
      sequences at the amino terminus, which have a resemblance to the carboxy-terminal
      portion of histone H1. Thus, Drosophila L22 and L23a might have two functions,
      namely the role of DNA-binding similar to histone H1 and the role of organizing
      the ribosome.

PMID- 9931509
TI  - House-fly cytochrome P450 CYP6D1: 5' flanking sequences and comparison of
      alleles.
AB  - CYP6D1 is a cytochrome P450 found in the house fly, Musca domestica. Expression
      is greater in pyrethroid-resistant vs. -susceptible strains and can be induced by
      phenobarbital in adult susceptible flies. CYP6D1 is expressed only in adult
      flies. To gain information about possible regulatory elements involved in CYP6D1
      expression, and to confirm the gene sequence that was previously determined by
      polymerase chain reaction (PCR), we screened a house-fly library prepared with
      genomic DNA from the pyrethroid-resistant LPR strain. A CYP6D1v1 clone was
      isolated and sequenced. This clone contained 887 nucleotides 5' to the open
      reading frame and a previously unknown 2.4-kb intron. Using polymerase chain
      reaction with primers based on the CYP6D1v1 allele, the sequences 5' to the ORF
      were obtained from five pyrethroid susceptible strains. The transcription
      initiation site (TIS) was identified at the same position in LPR and two
      susceptible strains (86 nucleotides upstream from the translation start site). A
      comparison of the 5' flanking sequences revealed a high degree of similarity for
      most regions, although differences in the sequences were identified. The possible
      roles of these sequence differences in regulation of CYP6D1 expression are
      discussed.

PMID- 9931510
TI  - Rat NAP1: cDNA cloning and upregulation by Mpl ligand.
AB  - The Mpl ligand is a hematopoietic cytokine which exerts its effects through
      association with the c-Mpl receptor. It regulates the proliferation,
      polyploidization and maturation of platelet precursors, the megakaryocytes. Using
      a differential display polymerase chain reaction (PCR) approach, we have
      identified an mRNA, belonging to a family of nucleosome assembly proteins, whose
      expression is upregulated in response to Mpl ligand. Multiple size classes of
      this mRNA (1.7, 2.5 and 4.3kb) are readily detected in rat primary bone marrow
      cells and hematopoietic tissues. The size classes are also expressed to different
      extents in cell lines of all hematopoietic lineages. We isolated the full-length
      cDNA encoding the rat megakaryocyte 1.7kb mRNA, referred to as rNAP1. Bacterially
      expressed recombinant protein encoded by the 1.7kb cDNA facilitates the formation
      of nucleosomes on relaxed circular DNA in vitro. Our data indicate that rNAPs,
      which may facilitate chromatin reorganization, are upregulated by Mpl ligand. It
      is possible that NAPs contribute to Mpl ligand's induced effects on hematopoietic
      cells.

PMID- 9931511
TI  - Isolation and expression of the genes encoding the acidic ribosomal
      phosphoproteins P1 and P2 of the medfly Ceratitis capitata.
AB  - The genes of the acidic ribosomal proteins P1 and P2 (CcP1 and CcP2) of the
      medfly Ceratitis capitata were isolated from a genomic library using homologue
      DNA probes prepared by PCR. Sequencing and characterization of the two genes
      revealed strong similarities of the encoded amino acid sequence to the homologous
      proteins of Drosophila melanogaster and other eukaryotic species. The predicted
      amino acid sequences of the CcP1 and CcP2 proteins shared an almost identical
      carboxyl terminal sequence of 10 amino acids common to most known acidic
      ribosomal proteins. The CcP2 gene lacked intervening sequences in contrast to the
      CcP1 gene, which was interrupted by an intron of 188 nucleotides. Both genes were
      cloned in expression pT7 vectors and were expressed in Esherichia coli. The 17-
      and 15-kDa recombinant proteins reacted with a monoclonal antibody specific to
      the highly conserved carboxyl terminus of eukaryotic acidic ribosomal proteins,
      confirming their equivalence to these ribosomal components. Both recombinant
      proteins were electrophoretically identical to acidic proteins extracted from
      purified ribosomes of C. capitata.

PMID- 9931512
TI  - Narcotic analgesia for ventilated newborns: are placebo-controlled trials ethical
      and necessary?

PMID- 9931513
TI  - The "inclusion benefit" in clinical trials.

PMID- 9931514
TI  - Relative antioxidant deficiency in obese children: A weighty contributor to
      morbidity?

PMID- 9931516
TI  - Alagille syndrome: A nutritional niche for Notch.

PMID- 9931515
TI  - Tissue transglutaminase: the Holy Grail for the diagnosis of celiac disease, at
      last?

PMID- 9931517
TI  - The pediatric growth curve as a cancer research tool.

PMID- 9931518
TI  - Home monitoring of 17 hydroxyprogesterone levels: "throw away the urine jug, mom,
      the filter paper just arrived".

PMID- 9931519
TI  - Diagnosing with both sides of the brain.

PMID- 9931520
TI  - Advantages of fentanyl over morphine in analgesia for ventilated newborn infants
      after birth: A randomized trial.
AB  - OBJECTIVE: To compare the efficacy and adverse effects of fentanyl or morphine
      analgesia during the first 2 days of life in newborn infants who underwent
      mechanical ventilation. STUDY DESIGN: In a randomized double-blind trial, 163
      infants were allocated to receive a continuous infusion of fentanyl (10.5
      microg/kg over a 1-hour period followed by 1.5 microg/kg/hr) or morphine (140
      microg/kg over a 1-hour period followed by 20 microg/kg/hr) for at least 24
      hours. The severity of pain was assessed with physiological parameters, a
      behavioral pain scale, and stress hormone concentrations before and 2 and 24
      hours after the start of treatment. RESULTS: The analgesic effect was similar in
      both groups, as judged by the pain scale. Plasma adrenaline and noradrenaline
      concentrations decreased significantly from 0 to 24 hours in both groups. Median
      adrenaline decrease was 0.5 nmol/L (interquartile range [IQR] 1.1;0.0) in the
      fentanyl and 0.7 nmol/L (IQR 1.3;0.1) in the morphine group, noradrenaline 2.1
      nmol/L (IQR 9.0;0.2), and 3.0 nmol/L (IQR 7. 5;0.3), respectively. beta-endorphin
      decreased significantly only in the fentanyl group ( 14 pmol/L (IQR 28; 7), P
      <.05). Decreased gastrointestinal motility was less frequent in the fentanyl
      group (23% vs 47%, P <.01). CONCLUSIONS: With at least as effective analgesia as
      with morphine, fentanyl had fewer side effects. Fentanyl may be superior to
      morphine for short-term postnatal analgesia in newborn infants.

PMID- 9931521
TI  - Do sick newborn infants benefit from participation in a randomized clinical
      trial?
AB  - BACKGROUND: Adult participants in randomized controlled trials often have better
      outcomes than patients who are eligible but not enrolled. OBJECTIVE: To examine
      whether newborn infants who were allocated to placebo in an investigational drug
      trial had better outcomes than infants who were eligible but not randomized
      (eligible NR). STUDY DESIGN: During a randomized controlled trial of antithrombin
      therapy in premature infants with respiratory distress syndrome, data were
      collected prospectively on all 76 infants in the eligible NR group. Study
      outcomes were compared with those of all 61 infants who were randomized to
      placebo. The same exogenous surfactant was used in all patients. RESULTS: In the
      placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational
      age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group,
      mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2.
      3) weeks, and 58% were male; 57% of infants in both groups had been exposed to
      steroids before birth. The median duration of mechanical ventilation was reduced
      from 6.2 days in the eligible NR group to 4. 8 days in the placebo group (P
      =.008). There was also a trend toward less frequent and less severe
      intraventricular hemorrhage in trial participants. CONCLUSIONS: These data are
      consistent with the hypothesis that sick newborn infants may benefit from
      participation in a randomized controlled trial.

PMID- 9931522
TI  - Predictors of intracranial hemorrhage during neonatal extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: To identify independent predictors of intracranial hemorrhage (ICH)
      during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: This
      retrospective cohort consisted of all neonates who did not have an ICH before
      treatment with ECMO identified in the Extracorporeal Life Support Organization
      Registry from 1992 to 1995 (n = 4550). Multiple logistic regression analysis was
      used to identify factors independently correlated with ICH and to develop a model
      that could be used to predict the risk of ICH in neonates treated with ECMO.
      RESULTS: ICH was identified in 9.9% of patients. The factors associated with ICH
      remaining after adjusting for other significant variables (P <.01) were
      gestational age (GA) <34 weeks (odds ratio [OR] 12.1, 95% confidence intervals
      [CI] [6.6, 22]), GA 34 to <36 weeks (OR 4.1, CI [2.9, 5.8]), GA 36 to <38 weeks
      (OR 2.1, CI [1.6, 2.8]) primary diagnosis of sepsis (OR 1.8, CI [1.4, 2.3]),
      epinephrine use (OR 1.9, CI [1.5, 2.5]), coagulopathy (OR 1. 6, CI [1.1, 2.2]),
      arterial pH <7.0 (OR 2.5, CI [1.6, 3.9]), and arterial pH 7.0 to <7.2 (OR 1.8 CI
      [1.3, 2.5]). ICH rates for neonates receiving venovenous versus venoarterial ECMO
      and for those treated with or without cephalic jugular venous drainage were not
      significantly different. CONCLUSIONS: Gestational age, acidosis, sepsis,
      coagulopathy, and treatment with epinephrine are major independent factors
      associated with ICH in neonates treated with ECMO. In particular, GA <34 weeks
      remains a major barrier for use of current ECMO technologies.

PMID- 9931523
TI  - Comparison of serum concentrations of alpha-tocopherol and beta-carotene in a
      cross-sectional sample of obese and nonobese children (NHANES III). National
      Health and Nutrition Examination Survey.
AB  - INTRODUCTION: Low intake of the fat-soluble antioxidants alpha-tocopherol and
      beta-carotene has been linked to greater risks of cardiovascular disease in
      epidemiologic studies. Obesity in adults is associated with lower levels of alpha
      tocopherol and beta-carotene, which may contribute to the increased risk of
      cardiovascular disease associated with obesity. AIM: To examine serum
      concentrations of fat-soluble antioxidants in a large, nationally representative
      sample of obese and nonobese children. METHODS: Serum levels of alpha-tocopherol
      and beta-carotene were measured in 6139 children between the ages of 6 and 19
      years enrolled in the National Health and Examination Survey, cycle III. Serum
      alpha-tocopherol levels were adjusted for fasting cholesterol and triglyceride
      levels. Nutritional intake was assessed by 24-hour dietary recall and food
      frequency questionnaires. RESULTS: Serum levels of beta-carotene were
      significantly lower in obese children compared with those found in normal weight
      children (0.22 0.14 micromol/L vs 0.29 0.17 micromol/L, P <.001). After
      adjustment was done for serum triglyceride and cholesterol levels, alpha
      tocopherol levels were also significantly lower in obese children (2.68 0.59 vs
      3.17 0.60, P <.001). Approximately one half of obese children had serum levels of
      beta-carotene and adjusted alpha-tocopherol in the lowest quartile compared with
      approximately one quarter of normal weight children (P <.001). No significant
      differences were seen in reported intake of beta-carotene, alpha-tocopherol,
      fruit, or vegetables between obese and nonobese children. CONCLUSION: Reduced
      serum levels of fat-soluble antioxidants are present in obese children.

PMID- 9931524
TI  - IgA antibodies to tissue transglutaminase: An effective diagnostic test for
      celiac disease.
AB  - OBJECTIVE: Tissue transglutaminase (tTG) is the main autoantigen recognized by
      endomysial antibodies. The aim of this study was to assess sensitivity,
      specificity, and predictive value of IgA and IgG antibodies to tTG in the
      diagnosis of celiac disease compared with endomysial antibodies. STUDY DESIGN: We
      established enzyme-linked immunosorbent assay procedures to measure IgA and IgG
      antibodies to tTG in sera from 48 untreated and 33 treated patients with celiac
      disease and from 63 patients with gastrointestinal disease who were in a control
      group. Sera from 10 patients with celiac disease were examined at various times
      after gluten was reintroduced into the patients' diet. RESULTS: Both IgA and IgG
      to tTG were significantly (P <.001) higher in serum of untreated patients with
      celiac disease versus those in the control group; IgA but not IgG was
      significantly (P <.001) higher in untreated versus treated patients with celiac
      disease. IgA and IgG antitissue tTG had a diagnostic sensitivity, specificity,
      and positive predictive value of 92% and 21%, 98% and 97%, and 98% and 83%,
      respectively. The concordance rate of IgA anti-tTG with IgA antiendomysial
      antibodies was 95%. In 5 of the 10 patients undergoing gluten challenge, IgA
      antiendomysium antibodies were detected earlier than IgA anti-tTG antibodies.
      CONCLUSIONS: tTG-based enzyme-linked immunosorbent assay is an effective
      diagnostic test, although immunofluorescent-based assays are more sensitive,
      particularly during gluten challenge.

PMID- 9931525
TI  - Growth, nutritional status, body composition, and energy expenditure in
      prepubertal children with Alagille syndrome.
AB  - OBJECTIVES: To describe the patterns of growth, nutritional status, body
      composition, and resting energy expenditure (REE) in prepubertal children with
      Alagille syndrome (AGS) before the onset of end-stage liver disease. STUDY
      DESIGN: Thirteen prepubertal subjects with AGS (8 male; mean age, 6.8 2.8 years)
      were evaluated for growth parameters, body composition by skinfolds and by dual
      energy x-ray absorptiometry, and REE by indirect calorimetry. The children with
      AGS were compared with a healthy, age-matched reference group of 37 prepubertal
      children. RESULTS: Compared with healthy children, children with AGS had
      significantly reduced (P <. 05) growth (weight, weight z score, height, height z
      score), nutritional status (midarm circumference, triceps skinfold, and midarm
      muscle area), and body composition (fat mass and fat-free mass). Subscapular
      thickness, percent body fat, and REE were not different. The AGS subgroup (n = 4)
      with REE greater than 110% predicted value had a reduced percent body fat (P
      <.02). CONCLUSIONS: Growth and body composition abnormalities are common in
      prepubertal children with AGS.

PMID- 9931526
TI  - Rapid somatic growth after birth in children with neuroblastoma: A survey of 1718
      patients with childhood cancer in Kyushu-Okinawa district.
AB  - OBJECTIVE: To evaluate the association of somatic growth from birth through
      diagnosis with the development of childhood cancer. METHODS: The weights and
      heights of 1718 children with cancers were determined and converted into standard
      deviation (SD) scores, both at birth and at diagnosis, by using the means and SD
      values of the general population. RESULTS: Among patients with neuroblastoma and
      acute lymphoblastic leukemia, the percentages of children with body weight and
      height over mean + 2 SDs were significantly higher at diagnosis than the expected
      value in the general population. The percentage of children with neuroblastoma
      and body weight over mean + 2 SD increased significantly from birth through
      diagnosis (P =.04). Although the medians of weight SD scores decreased from birth
      through diagnosis in patients with representative cancers except for
      neuroblastoma, the value significantly increased in patients with neuroblastoma
      diagnosed before 1 year of age (P =.03), especially in those whose cancer was
      detected by mass screening at 6 months of age (P <.01). CONCLUSIONS: Rapid
      somatic growth from birth through diagnosis in patients with neuroblastoma
      diagnosed before 1 year of age suggests a possible involvement of certain growth
      factors in these patients.

PMID- 9931527
TI  - Home monitoring of 17 hydroxyprogesterone levels in congenitx127drenal
      hyperplasia with filter paper blood samples.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of 17
      hydroxyprogesterone (17OHP) determination in dried filter paper blood samples
      from patients with congenital adrenal hyperplasia caused by 21-hydroxylase
      deficiency. It was hypothesized that these home samples would enhance patient
      treatment. STUDY DESIGN: Results of 17OHP determination in simultaneously
      collected venous and dried filter paper blood samples were compared to establish
      assay reliability. Thereafter, parents mailed dried filter paper blood samples
      collected before each hydrocortisone dose. RESULTS: The 17OHP levels in wet and
      dried blood samples correlated well (r = 0.98). Results did not change when
      stored for 2 weeks under various conditions. Blood sampling at different times of
      the day provided insights into the patterns of 17OHP secretion and identified
      times of inadequate adrenal suppression. Dose adjustments were then made
      considering the time of day when adrenal suppression was inadequate. CONCLUSION:
      Home monitoring of 17OHP is a reliable and practical approach for assessing
      adrenal steroid activity in patients with congenital adrenal hyperplasia.
      Considering the time of day of 17OHP elevations also facilitates hydrocortisone
      dosing adjustment.

PMID- 9931528
TI  - Estrogen levels in girls with premature thelarche compared with normal
      prepubertal girls as determined by an ultrasensitive recombinant cell bioassay.
AB  - OBJECTIVE: Estradiol levels in girls with premature thelarche have not previously
      been well defined because of the lack of adequate sensitivity of previously
      available estradiol assays. The ultrasensitive recombinant cell bioassay for
      estradiol has made the study of estradiol levels in premature thelarche possible.
      We hypothesized that girls with premature thelarche have higher estradiol levels
      than normal prepubertal girls. STUDY DESIGN: We used an ultrasensitive
      recombinant cell bioassay to study estradiol levels in 20 girls with premature
      thelarche and 15 normal prepubertal girls less than 3 years of age. The 2 groups
      were compared by Student t test. RESULTS: Estradiol levels were significantly
      greater in the girls with premature thelarche (8.4 4. 5 pmol/L estradiol
      equivalents) than in the normal prepubertal girls (3.3 3.5 pmol/L estradiol
      equivalents; P <.01). The estradiol level was not significantly correlated with
      age, height, weight, body mass index, age at onset of thelarche, or the presence
      or absence of ovarian cysts. CONCLUSION: Girls with premature thelarche have
      significantly higher estradiol levels than normal prepubertal girls. This is
      consistent with the hypothesis that the mechanism of premature thelarche involves
      increased estradiol levels rather than increased sensitivity of breast tissue to
      normal estradiol levels.

PMID- 9931529
TI  - Psychoeducational profile of the 22q11.2 microdeletion: A complex pattern.
AB  - OBJECTIVES: To examine the psychoeducational profile associated with the
      chromosome 22q11.2 microdeletion (DiGeorge/velocardiofacial syndrome). STUDY
      DESIGN: Thirty-three patients (aged 6 to 27 years) with a 22q11.2 microdeletion
      underwent psychoeducational testing as part of a comprehensive evaluation.
      Nonparametric statistics were used to compare verbal and performance IQ, academic
      achievement scores, and receptive versus expressive language scores. Post hoc
      comparisons were made of IQ subtest scores and of language versus verbal IQ.
      RESULTS: Full-scale IQ ranged from the normal to the moderately retarded range.
      Mean verbal IQ was significantly higher than mean performance IQ. In a similar
      manner, mean reading and spelling scores were superior to the mean mathematics
      score, although achievement scores typically were in the range of verbal IQ. In
      addition, many children showed clinically significant language impairments, with
      mean language scores lower than mean verbal IQ. CONCLUSIONS: The IQ and academic
      profiles are reminiscent of a "nonverbal learning disability," although
      achievement was not discrepant from IQ. The coincidence of language impairment
      with a relative strength in reading belies a unique neuropsychologic profile.
      Educational programming for these children must address both verbal and nonverbal
      deficits.

PMID- 9931530
TI  - Clinical significance of lupus anticoagulants in children.
AB  - OBJECTIVES: To determine the spectrum of associated clinical manifestations and
      time course of lupus anticoagulants (LA) in children. STUDY DESIGN: Retrospective
      study of 95 consecutive children (46 boys and 47 girls), with a median age of 5.3
      years (range, 1.7 to 17.1 years), diagnosed with presence of LA at a hemostasis
      referral center; 83 were followed up over a median of 2.9 years (range, 6 weeks
      to 21.6 years). RESULTS: At diagnosis, 80 of 95 (84%) children were free of
      symptoms, and presence of LA was found incidentally. Nine children (10%) had
      bleeding symptoms, 5 (5%) had thrombotic events, and 1 had systemic lupus
      erythematosus. Among the patients with bleeding, 5 had transient severe
      hypoprothrombinemia after adenovirus infections, and 3 had thrombocytopenia. None
      of the children who were initially free of symptoms had bleeding, thrombotic
      complications, or autoimmune disease subsequently. At follow-up, 48 of 83 (58%)
      patients had normal activated partial thromboplastin time values after 1.9 years
      (5 weeks to 19.1 years). Thirty-two (38%) still had activated partial
      thromboplastin time elevations but did not fulfill all criteria for presence of
      LA after 3.2 years (7.4 months to 9.3 years). Three (4%) patients, who had
      presented with thrombosis, had persistent positive LA, anti-cardiolipin, and
      antinuclear antibodies after 1.4, 2.8, and 7.5 years, respectively. One of these
      had recurrent thrombosis. CONCLUSIONS: In most children the presence of LA did
      not lead to clinical complications and was transient. Bleeding occurred with
      additional hypoprothrombinemia or thrombocytopenia. Thrombosis was rare and
      strongly associated with persistently positive LA.

PMID- 9931531
TI  - Medical complications in long-term survivors with X-linked myotubular myopathy.
AB  - OBJECTIVES: X-linked myotubular myopathy (MTM1) is a rare developmental disorder
      of skeletal muscle characterized by the presence of central nuclei in biopsy
      specimens from affected male subjects. Until recently, the disorder was usually
      fatal within the first year of life. This study was undertaken to determine the
      outcome in long-term survivors (>1 year of age) with MTM1. METHODS: Clinical data
      were obtained on 55 male subjects from 49 independent North American families for
      which a mutation was identified in the X-linked myotubularin gene by direct
      genomic sequencing. Medical records were reviewed and families were interviewed
      to ascertain features at birth, length of survival, developmental milestones, and
      medical complications. RESULTS: Seventy-four percent (26 of 35) of the affected
      male subjects over the age of 1 year are living (range, 1 to 27 years); 80%
      remain completely or partially ventilator-dependent. In the absence of
      significant hypoxia, cognitive development is normal, and the muscle disorder
      appears nonprogressive. Several patients have had other medical problems not
      previously reported to be associated with MTM1. These include pyloric stenosis (4
      male subjects from 3 families), spherocytosis (2 patients), gallstones (4
      patients), kidney stones or nephrocalcinosis (2 patients), a vitamin K responsive
      bleeding diathesis (2 patients), and height >/=90% for age (40% of the patients).
      Six patients have had biochemical evidence of liver dysfunction, and 2 patients
      died after significant liver hemorrhage. CONCLUSIONS: These data suggest that the
      prognosis for X-linked MTM may not be as poor as previously reported. However, at
      least some long-term survivors appear at risk for medical complications involving
      other organ systems, and patients should be carefully monitored for these
      potentially life-threatening complications. The pleiotropic symptoms demonstrated
      in these patients strongly suggest that the function of the MTM1 protein is not
      limited to developing muscle cells.

PMID- 9931532
TI  - Growth hormone improves body composition, fat utilization, physical strength and
      agility, and growth in Prader-Willi syndrome: A controlled study.
AB  - BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS)
      are accompanied by abnormal body composition and diminished energy expenditure
      resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS
      often includes decreased growth hormone (GH) secretion, suggesting a possible
      therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6
      months of observation to determine baseline growth rate, and with the use of a 12
      month randomized controlled study design, the effects of GH treatment (1 mg/m2/d)
      on growth, body composition, strength and agility, pulmonary function, resting
      energy expenditure (REE), and fat utilization were assessed in 54 children with
      PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral
      density were measured by dual x-ray absorptiometry. Indirect calorimetry was used
      to determine REE and to calculate respiratory quotients. RESULTS: Stimulated
      levels of GH in response to clonidine testing were low in all patients (peak, 2.0
      ng/mL). After 12 months, GH-treated subjects showed significantly increased
      height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent
      body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory
      muscle function, physical strength, and agility (sit-ups, weight-lifts, running
      speed, and coordination). A significant decline in respiratory quotients occurred
      during GH therapy (0.81 to 0.77, P <.001), but total REE did not change.
      CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased
      percent body fat, and increased fat oxidation but did not significantly increase
      total REE. Improvements in respiratory muscle strength, physical strength, and
      agility also occurred, suggesting that GH treatment may have value in reducing
      some physical disabilities experienced by children with PWS.

PMID- 9931534
TI  - The neonatal presentation of Prader-Willi syndrome revisited.
AB  - We describe 6 newborns evaluated for hypotonia, later diagnosed with Prader-Willi
      syndrome despite the absence of the classical neonatal features of this syndrome.
      Specific genetic testing for Prader-Willi syndrome should be considered for all
      neonates with undiagnosed central hypotonia even in the absence of the other
      major features of this syndrome.

PMID- 9931533
TI  - Body fat determined by skinfold measurements is elevated despite underweight in
      infants with Prader-Labhart-Willi syndrome.
AB  - Body composition and leptin were studied in 13 young, still underweight and 10
      older overweight children with Prader-Labhart-Willi syndrome. Not only the older
      overweight children but also the young underweight children had elevated skinfold
      standard deviation scores for body mass index and elevated body mass index
      adjusted leptin levels, suggesting relatively increased body fat despite
      underweight. Our data indicate that body composition in Prader-Labhart-Willi
      syndrome is disturbed already in infancy, long before the onset of obesity.
      Leptin production appears to be intact.

PMID- 9931535
TI  - Effect of pulsed dexamethasone therapy on tolerance of intravenously administered
      lipids in extremely low birth weight infants.
AB  - We investigated the effect of dexamethasone on parenteral lipid tolerance in 7
      day-old extremely low birth weight infants (n = 28) in a randomized, double-blind
      trial. Serum triglycerides were measured before and after 3 days of dexamethasone
      or placebo treatment. Infants treated with dexamethasone responded with higher
      triglyceride concentrations and greater sensitivity to incremental increases in
      the intravenous lipid dose.

PMID- 9931536
TI  - Failure of intravenously administered immunoglobulin in the treatment of neonatal
      myasthenia gravis.
AB  - Neonatal myasthenia gravis is uncommon and life threatening. We describe the use
      of intravenously administered immunoglobulin, in addition to conventional
      modalities, in a neonate with severe neonatal myasthenia gravis. However, despite
      this aggressive management, the child had a prolonged period of weakness
      requiring intensive care.

PMID- 9931538
TI  - Treatment of ataxia in isolated vitamin E deficiency caused by alpha-tocopherol
      transfer protein deficiency.
AB  - Dysfunction of the alpha-tocopherol transfer protein causes ataxia with isolated
      vitamin E deficiency. A 14-year-old male patient presented with ataxia and mental
      symptoms caused by a homozygous (552G-->A) alpha-tocopherol transfer protein
      mutation. After initiation of high-dosage alpha-tocopherol therapy, the organic
      mental syndrome disappeared and cognitive function improved rapidly. Neurologic
      recovery, however, was slow and incomplete.

PMID- 9931537
TI  - Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric
      protein intolerance.
AB  - We describe 4 cases of lysinuric protein intolerance, which all fulfilled the
      diagnostic criteria for hemophagocytic lymphohistiocytosis. Mature histiocytes
      and neutrophil precursors participated in hemophagocytosis in the bone marrow.
      Moreover, serum levels of ferritin and lactate dehydrogenase were elevated,
      hypercytokinemia was present, and soluble interleukin-2 receptor levels were
      increased up to 18.6-fold. The diagnosis of lysinuric protein intolerance should
      therefore be considered in any patient presenting with hemophagocytic
      lymphohistiocytosis.

PMID- 9931540
TI  - Congenital mesoblastic nephroma: A rare cause of perinatal anemia.

PMID- 9931539
TI  - Splenic abscess in a patient with type 3 Gaucher's disease receiving enzyme
      replacement therapy.
AB  - We report the rare complication of a splenic abscess in an 11-year-old girl with
      type 3 Gaucher's disease, massive splenomegaly, and a splenic cyst after
      commencement of enzyme replacement therapy. This case highlights potential
      difficulties in establishing the diagnosis of splenic abscess in the presence of
      pre-existing splenic pathology.

PMID- 9931541
TI  - Vitamin E for ROP.

PMID- 9931542
TI  - Reply 

PMID- 9931543
TI  - Ethical issues of placebo-controlled trials.

PMID- 9931544
TI  - Preferential pharyngeal colonization of methicillin resistant Staphylococcus
      aureus in infants.

PMID- 9931545
TI  - Effect on growth of inhaled steroid therapy.

PMID- 9931546
TI  - Comment: Response to an article by Hamilton et al. on 'Effects of colony
      stimulating factor-1 on human extravillous trophoblast growth and invasion'.

PMID- 9931547
TI  - REPLY FROM AUTHOR. Possible explanation for opposite responses of EVT and TCL-1
      cells to endogenous CSF-1 

PMID- 9931548
TI  - Reply 

PMID- 9931550
TI  - Reply 

PMID- 9931549
TI  - Behcet's disease in children.

PMID- 9931551
TI  - Increased TSH levels in neonates with congenital malformations.

PMID- 9931552
TI  - Infant Hib vaccination and herd immunity.

PMID- 9931553
TI  - [Symposium on the occasion of the 70th birthday of Prof. Th. N. Waubke, M.D.,
      Ophthalmology Clinic of the Essen University].

PMID- 9931554
TI  - [Atencion Primaria: towards a journal with a Mediterranean and South European
      dimension].

PMID- 9931555
TI  - [Induced prescription: excuse or reality?].

PMID- 9931556
TI  - [Comparison of family physicians' and gynecologists' use of the intrauterine
      device (IUD)].
AB  - OBJECTIVE: To quantify differences between general practitioners (GPs) and
      gynaecologists in the technique of insertion and follow-up of the intra-uterine
      device (IUD). DESIGN: Multicentred, descriptive, longitudinal study. SETTING: Two
      urban health centres and a family guidance clinic. PARTICIPANTS: Target
      population (n = 1700) between January 1993 and January 1996. Estimated mean of
      complications was 25%. Sample size was 247 for alpha = 0.05 and 1-alpha = 0.95.
      The sample was extended to 300 to allow for possible losses of files, estimated
      at 20%. MEASUREMENTS AND MAIN RESULTS: The variables age, sex, marital status,
      educational level, parity, abortions, previous contraception, type of job, type
      of IUD, post-insertion and follow-up complications, subjective evaluation,
      removal and average follow-up time, were analysed. 158 (54.9%) of the 288 IUDs
      finally studied were inserted by GPs, and 130 (45.1%) by gynaecologists. 69.5%
      were anchor-shaped, and 30.5% T-shaped. In 85.5% no immediate complications were
      found. Mean follow-up time was 22.67 months (CI 95%, 21.3-24.0), during which
      time 36.6% had complications detected, which led to removal of the device in
      22.3% of complications. We found no statistically significant differences between
      the two populations for age, marital status, subjective evaluation, number of
      abortions, parity or previous contraception. Likewise, no differences between
      G.P.s and gynaecologists were detected for post-insertion or follow-up
      complications, percentage of IUDs removed, or period of time evaluated. There
      were differences found for the type of IUD used, with more anchor-shaped IUDs in
      primary care. There were no differences for the type of IUD or complications
      requiring its removal. CONCLUSIONS: In the population studied we found no
      differences in immediate or later complications between IUDs inserted by GPs and
      by gynaecologists.

PMID- 9931557
TI  - [Overattendance at primary care: a study of psychosocial factors].
AB  - OBJECTIVE: To determine the effect of various psychological and social factors-
      family function, social support, psychological malaise and social class--on
      frequency of attendance. DESIGN: Study with cases and controls. SETTING: Health
      Districts Girona-3 and La Bisbal. PARTICIPANTS: Criteria for inclusion: being
      older than 14, being on a list as a user, and having been seen at least once
      during the study period. The person over-attending is defined as someone
      attending 7 or more times in a year. The normal attender attends less than 7
      times. The sample was 441 patients (209 cases and 232 controls). MEASUREMENTS AND
      MAIN RESULTS: The Smilkestein family Apgar and the DUKE-UNC social support
      questionnaires, and the Goldberg anxiety and depression scale, were administered.
      Social class was defined according to the job of the head of the family.
      Statistical analysis was undertaken in two steps: firstly, bivariate analysis;
      and second, multivariate. The social support and age variables were related to
      frequency of attendance: they explained 8.1% of it (through multiple regression).
      Depression increased by between 1.21 and 2.58 the risk of over-attending and
      explained 10.53% of the variability of over-attendance, in line with the
      logistical regression analysis. CONCLUSIONS: The psychological and social
      variables studied fail to explain most of the variability. We should demystify
      the importance of psychological and social factors in the use of health
      resources.

PMID- 9931558
TI  - [Validity of semiquantitative methods of microalbuminuria screening in diabetes
      mellitus].
AB  - OBJECTIVE: To analyse the validity of the Micraltest and Microbumintest semi
      quantitative methods for microalbuminuria screening in type 2 diabetes mellitus
      in primary care clinics. DESIGN: Crossover study to validate diagnostic tests.
      SETTING: Three general practices at an urban health centre. PATIENTS: Consecutive
      sample of 64 diabetics not dependent on insulin. MEASUREMENTS AND MAIN RESULTS:
      Each patient's own doctor performed in the consultation the semi-quantitative
      determinations in a simple sample of the morning's first urine. As standard, a
      rate of albumin excretion above 20 micrograms/min, determined by
      immunonephelometry in a 2-hour controlled time sample, was used. The prevalence
      of Microalbuminuria was 25% (C.I. 95%, 14.4-35.6). The sensitivity of Micraltest
      was 69% (CI, 42-88), and its specificity 52% (CI, 37-67), corresponding to the
      cut-off point of 10 mg/L. The sensitivity of Microbumintest was 63% (CI, 36-84),
      and its specificity 67% (CI, 52-79). The combination of both tests in one sample
      had 75% sensitivity (CI, 47-92) and 44% specificity (CI, 30-59). Negative
      predictive values ranged between 84 and 85%. CONCLUSIONS: The semi-quantitative
      microalbuminuria detection tests are of limited use in the primary care clinic.
      Their sensitivity and the negative predictive value obtained in an isolated
      sample do not seem acceptable for a screening method.

PMID- 9931559
TI  - [Characteristics of the leadership of health center coordinators in the
      autonomous community of Murcia].
AB  - OBJECTIVE: To describe the style and effectiveness (adaptability) of the
      leadership of coordinators of an autonomous community according to the model of
      leadership on the ground, analysing its relationship with the work environment.
      DESIGN: Observational crossover study. SETTING: All the functioning teams in this
      community. PARTICIPANTS: Medical and nursing coordinators. MEASUREMENTS AND MAIN
      RESULTS: Hersey and Blanchard's questionnaire on leadership on the ground was
      employed. This identifies 1) the predominant style (scoring for style 0-12). On
      the approach of the coordinator to personal relationships and/or task
      development, it identifies 4 points: direction, persuasion, participation,
      delegation. 2) Adaptability of the manager (ranging from +24 to -24), based on
      that the best choice between different options depends on the maturity of the
      group. To contrast work environment and leadership, a validated questionnaire,
      adapted to our milieu, was used. Overall reply rate (51 coordinators) was 89.4%.
      Analysis of styles was: persuasive 5.05 points (SD = 1.25), participatory 4.74
      (SD 1.76), directive 1.2 (SD 1.11) and delegating 0.34 (SD 0.68). Adaptability
      scored 8.38 points (SD = 4.67), and was greater for the nursing coordinators (p <
      0.002) without differences for type, place or teaching qualifications. The work
      environment, both overall and by dimensions, correlated with adaptability,
      although no relationship was found with leaders' styles. CONCLUSIONS: Leadership
      adaptability was quite high and greater in nursing. The most prevalent styles
      were the persuasive and the participatory, more efficacious in teams of average
      maturity. Theoretical effectiveness was positively related to a better work
      environment.

PMID- 9931560
TI  - [Current situation of goiter endemic and iodine intake in the population of the
      Pyrenees and the Segria region of Lleida].
AB  - OBJECTIVE: To assess the prevalence of goiter in five areas of the Pyrineans and
      in the region of Segria in Lleida. DESIGN: Transversal descriptive study.
      SETTING: Five Pyrinean's regions and Segria. PATIENTS: Randomised selection of a
      sample of 601 subjects from the population over 6 years old. MEASUREMENTS: The
      field work, which was preceded by an informative campaign in the media, was
      carried out from October of 1994 through February of 1995. Survey with a personal
      interview, blood pressure, weight, height, goiter palpation, blood analysis with
      thyroidal hormones and urine analysis with the iodine/creatine ratio
      determination. RESULTS: The prevalence of goiter was 18.3% which was higher among
      women, the ratio being 3.7/1 (women/men). No significant differences were found
      in regard to geographic distribution. Mean iodinuria was 120 micrograms/l, though
      it was below 50 in 11.1% subjects. The prevalence of goiter has been founded to
      be related to age, increasing from the age of 45 onwards. Higher percentage of
      goiter was found among individuals with a family history of the disease and women
      who have had children. The prevalence of hypothyroidism was 3.4%. CONCLUSIONS: We
      have found a medium degree of goiter's endemia in the study area, the mean
      iodinuria in the population is in normal range. The women with children have a
      higher prevalence of goiter probably due to a lack of sufficient iodine intake
      being a subgroup at risk.

PMID- 9931561
TI  - [Epidemic outbreak in a home for the aged caused probably by Bacillus cereus].
AB  - OBJECTIVES: To identify the causative agent and the factors precipitating the
      outbreak. DESIGN: Observational, crossover study. SETTING: Las Delicias Health
      district, Jerez de la Frontera. PATIENTS AND OTHER PARTICIPANTS: The population
      exposed, belonging to an elderly persons' home. MEASUREMENTS AND MAIN RESULTS:
      The total number of people exposed was the 425 persons living in an elderly
      persons' home in Jerez in November 1995. The clinical histories were reviewed,
      and a specific questionnaire used to interview 77 ill persons and 77 healthy
      ones. The criteria for ill cases were presence of vomiting and/or diarrhoea.
      32.6% of the ill people had fundamentally vomiting; 24.67% diarrhoea, 37.66%
      vomiting plus diarrhoea, and 100% ran no temperature. Positive and significant OR
      were detected in various foods (from 2.36 to 10.52 OR). We isolated 3,000,000,
      and up to 5,600,000, colonies of Bacillus cereus per gram in several foods. We
      observed incorrect practices in the conservation and handling of foods.
      CONCLUSIONS: Epidemiological, microbiological and clinical indications placed us
      before an outbreak of food poisoning probably caused by Bacillus cereus. The
      intervention at critical points, inter-institution coordination and communication
      in time and with data between professionals (microbiologist, doctors, nurses,
      vets and epidemiologist) were decisive in solving the outbreak.

PMID- 9931562
TI  - [Doctor, I come from emergency service!].
AB  - OBJECTIVE: To identify the risk factors responsible for the high demand for care
      from patients coming via casualty to the general medicine and paediatrics clinics
      at our health centre. DESIGN: Observational study. SETTING: Primary care.
      Panaderas II Health Centre, Madrid. PATIENTS: All the patients attending the
      paediatrics and/or general medicine clinic via casualty in October 1996 were
      included (636). At random, 209 patients were selected from those who attended on
      demand. MEASUREMENTS AND MAIN RESULTS: For each patient the following variables
      were gathered: emergency/appointment, age, sex, room assigned, whether they asked
      for appointment, hour of call, type of emergency, clinic where seen, delay in
      appointment, assigned to which doctor's list, paediatrician/general practitioner.
      Being a girl was a significant risk factor in paediatrics casualty. In general
      practice, belonging to clinics with longer waits for an appointment and more
      patients per doctor (OR > 2) brought a higher risk, though not significantly, of
      attendance for consultation via casualty. Young people attended more frequently
      via casualty (chi 2 = 6.55, p = 0.01). CONCLUSIONS: The increase in each doctor's
      patient list generates attendance overload and anomalous paths for consultation.
      Limiting accessibility of the population does not control demand and increases
      the route via casualty. The doctor should assess personally those urgent requests
      not controlled by the clerical staff. Special attention to the young is probably
      needed to find the causes of the increase in emergency consultations among this
      population group.

PMID- 9931564
TI  - [Homeopathy or "viagra"].

PMID- 9931563
TI  - [What is the goal of health education and community activities in primary care?].

PMID- 9931565
TI  - [Primary care: guilty or innocent?].

PMID- 9931566
TI  - [Helicobacter pylori: 6-day triple therapy in duodenal ulcer. Study Group of
      Helicobacter pylori (GEHPY)].

PMID- 9931567
TI  - [Helicobacter pylori].

PMID- 9931568
TI  - [Amaryl and alapryl: 2 paronymous drugs].

PMID- 9931569
TI  - [Evaluation of 3 strategies to improve therapeutic compliance of patients with
      essential hypertension].

PMID- 9931570
TI  - [Diagnosis of early phase diffuse axonal injury using immunohistochemical
      methods].
AB  - Histologic and immunohistochemical investigation of the brain aimed at diagnosis
      of diffuse axonal injury (DAI) was performed in a group of 12 persons deceased of
      craniocerebral injury. Traumatic axonal change was visualized by
      immunohistochemical positivity of ubiquitin, low-molecular neurofilaments, beta
      amyloid precursor protein and neuron-specific enolase. In addition, H-E stain and
      silver impregnation of axons according to Palmgren were performed. Diffuse axonal
      injury was found in 7 cases (58%). In persons surviving more than 12 hours,
      morphological diagnosis of DAI was based on the finding of so called retraction
      balls. In person deceased in the first hours after injury, the retraction balls
      had not been formed yet and DAI was diagnosed according to histochemistry of
      axonal lesion. The earliest diagnosis of DAI was established 2 hours after injury
      when axonal lesion showed an immunohistochemical positivity with anti-neuron
      specific enolase. In a control group of 6 sudden death cases, axonal oedema was
      also found but lacking immunohistochemical positivity. Immunohistochemical proof,
      specially of neuron-specific enolase, seems to be inevitable for diagnosis of
      early phase DAI when the traumatic etiology of axonal deformities is to be
      distinguished from possible artificial lesions.

PMID- 9931571
TI  - [Immunohistochemical findings in the heart conduction system].
AB  - Immunohistochemical investigation of heart conductive system showed that
      degenerative changes described by James (9) in some cells of the system had a
      nature of programmed death. Extinction of certain of number of cells of a
      reducted part of the system was found in membranous septum. Apoptotic antigen
      (21) could be proved in some destructed cells by using anti-Bax and anti-bcl-2
      antibodies.

PMID- 9931573
TI  - Clinical prediction rules as guides to treatment.

PMID- 9931572
TI  - [Verification and determination of opiates in the urine and blood with thin-layer
      chromatography followed by densitometry in fatal cases of drug abuse].
AB  - Urine and blood concentrations of free and total morphin or 6-monoacetylmorphin
      were presented in fatal cases of morphin type opiates abuse. A solid phase
      extraction method was developed for isolation of drugs and their metabolities
      from biological material which used Separcol small columns with non-polar
      contents SI C 18T. Thin layer chromatography with densitometry anabled screening
      for quality evaluations. Resultes were compared with those obtained by
      fluoropolarizing immunodetection on Abbotts TDxFLx device. Possibility and cause
      of false positive results were discussed when using initial, screening,
      commercially available immunotests.

PMID- 9931574
TI  - Irregular rhythm in a man with unstable angina.

PMID- 9931575
TI  - Limiting acute renal failure.
AB  - Although the cause may be inadequate blood flow or a toxic insult to the renal
      tubules--or a combination thereof--iatrogenesis often underlies acute renal
      failure. Awareness of the procedures and treatments most likely to precipitate
      renal failure can help physicians to prevent the condition, or at least to detect
      it at the earliest opportunity.

PMID- 9931576
TI  - Silencing chronic cough.
AB  - The cause can almost always be identified. Postnasal drip syndrome, asthma, or
      gastroesophageal reflux disease account for most cases. The differential
      diagnosis also includes ACE inhibitor therapy, pertussis, and, in up to 80% of
      patients, multiple causes. Response to treatment may offer diagnostic
      confirmation but can be slow in coming.

PMID- 9931577
TI  - Angiogenesis inhibitors as cancer therapy.
AB  - Angiogenesis inhibitors target a tumor's need to obtain nourishment from the
      host. In general, they are predicted to be chiefly cytostatic--that is, they
      stabilize tumors and perhaps prevent metastasis rather than being curative.
      Nevertheless, it remains conceivable that these agents may trigger tumor cell
      death. Novel evaluative strategies will be essential to define their potential
      roles.

PMID- 9931579
TI  - Preventing the sequelae of compartment syndrome.

PMID- 9931578
TI  - Treatment of antidepressant-induced sexual dysfunction.
AB  - Sexual dysfunction is a common side effect seen in patients taking selective
      serotonin reuptake inhibitors. Spontaneous resolution may occur in some patients,
      but modifications to therapy can be employed to eliminate undesirable side
      effects. These include reducing drug dosages, altering timing of drug dosages,
      taking drug holidays, adding an adjunctive drug, and switching to alternative
      antidepressants.

PMID- 9931580
TI  - Crucial decision points in hospital care.

PMID- 9931581
TI  - Weight loss--despite a voracious appetite--and heat intolerance.

PMID- 9931582
TI  - [New approaches in surgery--visceral surgery in the tension field between trauma
      from surgical access and radicality].
AB  - The introduction of laparoscopic surgery (LS) and the circumstances under which
      LS could improve the prognosis of patients suffering from malignant diseases has
      made the development of abdominal surgery very important during the last decade.
      It also has heightened our awareness of operative trauma, which is not just
      relevant for cosmetic reasons, the consumption of pain killers, or the stay in
      hospital. It also seriously affects the immune system of the patient and, in
      itself, operative trauma can be determined to the patient's disease. A
      minimalization of operative trauma is one surgical goal, especially in oncologic
      patients, but a limitation of the surgical access leads to oncologic risks which
      arise from the subsequent "handling" of the tumor. The high risk of released
      tumor cells has already been proven by the evidence of tumor cells in the
      peritoneal lavage and the detection of so-called port-site metastasis. For
      oncologic surgery reducing the trauma caused by the tumor is more important than
      reducing the trauma caused by the surgical access.

PMID- 9931583
TI  - [Biological osteosynthesis].
AB  - A historic review distinguishes three periods in the treatment of fractures: The
      conservative period (approximate reduction and immobilization in traction or
      plaster cast), the mechanical and operative period (exact anatomical reduction
      and stable--even rigid--fracture fixation), and the biological and mechanical
      period (stability with strict attention to the biological environment of the bone
      circulation). Biological fracture fixation means: conservation of bone perfusion,
      protection of the soft tissue envelope and reduction of systemic stress by
      strengthening the host-defense mechanism. For preoperative planning, the
      following points have to be considered: choice of fixation method, reduction
      technique (open, closed, additional aids), surgical tactics (approach), and intra
      and postoperative adjuvant therapy.

PMID- 9931584
TI  - [Ileo-cecal segment as stomach substitute].
AB  - In clinical practice a long Roux-en-Y reconstruction is most often used for
      gastric replacement. Among various postgastrectomy symptoms, alcaline reflux is
      the most disturbing. A great variety of different pouch reconstructions with or
      without duodenal bypass only control reflux in part. The ileocoecal interposition
      has been placed between the oesophagus and the duodenum as a gastric substitute
      in 14 patients without postoperative mortality. This preliminary series
      demonstrates an excellent control of alcaline reflux and a good quality of life,
      according to the Eypasch score. Dysphagia or stasis in the distal oesophagus are
      absent as is gas bloating. This type of reconstruction, which is simpler than
      some of the pouch reconstructions, probably deserves more attention and may
      perhaps be perfected by varying the length of ileum and volume of ascending colon
      to be interposed.

PMID- 9931585
TI  - [Understanding microcirculation deficits as the key to surgical planning in
      visceral surgery].
AB  - It was the aim of our investigation to analyse microcirculatory disorders in
      order to optimize surgical decision-making intra- and perioperatively. Acute
      pancreatitis: The surgical principle to operate less and later is based on an
      improved ICU therapy. Using intravital microscopic quantification of pancreatic
      microcirculation it could be shown experimentally that in the early phase
      pancreatic necroses can be limited by improvement of pancreatic microcirculation.
      Hemodilution with dextran is superior to other regimens. Liver resection: The
      expansion of liver resections requires a reduction of ischaemia/reperfusion
      injury. Preconditioning of the liver, i.e. induction of short-term ischaemia
      prior to the main ischaemic period, results in an induction of protective
      mechanisms with increased tolerance to ischaemia. Liver transplantation: Liver
      microcirculation is a reliable parameter to predict graft quality
      intraoperatively and to monitor therapeutic approaches to ischaemia/reperfusion
      injury. With the analysis of microcirculatory disorders, a basic understanding
      for organ dysfunctions which lead to operation or are a result of surgical
      therapy can be gained.

PMID- 9931586
TI  - [Synopsis of modern tumor therapy with molecular biology methods].
AB  - The therapy of gastrointestinal cancer is currently based on the surgical removal
      of the primary tumor or the metastases, respectively. A major improvement of the
      five year survival rate or an effective cure from advanced tumors will mainly
      depend on adjuvant therapeutic concepts even after surgical R0-resection. Such
      concepts can be developed nowadays with major expectations for success based on
      our advanced molecular biological knowledge on (i) increased proliferation, (ii)
      reduced apoptosis rate, (iii) the dissemination and (iv) the mechanisms of
      invasive growth of malignant cells.

PMID- 9931587
TI  - [Significance of molecular biology research for trauma surgery exemplified by
      wound and bone healing].
AB  - During the past years molecular biology has become increasing interesting for
      medical research. These techniques allow the identification of intra-, extra- and
      intercellular mechanisms, which are important for physiological and
      pathophysiological processes. Because healing takes place at the cellular level,
      molecular biology is also relevant for traumatological research. As of yet, there
      are only a few papers which deal with molecular biological and traumatological
      problems. For this reason, we only have little knowledge of the function of genes
      and proteins during wound and fracture healing, for example. To demonstrate the
      possibilities of molecular biology, we present an experimental strategy by which
      these techniques can help to answer special traumatological questions.

PMID- 9931588
TI  - [The Human Genome Project and its consequences for surgery].
AB  - The Human Genome Project is an international effort to discover all 80,000 genes
      of the human genome and to determine the complete sequence of the three billion
      basepairs of the human DNA. Chromosome mapping enables fragmentation of large DNA
      pieces, sequencing of the resulting small fragments and realignment in the order
      in which they originally occurred in the chromosomes. Identification of genes
      involved in various benign and malignant diseases will lead to the understanding
      of their action and will result in prevention-based medical approaches. In
      addition, novel therapeutic regimens will be devised based on human gene
      products. Decipherment of the genetic programs of embryogenesis will enable
      regeneration of various tissues without the formation of scars.

PMID- 9931589
TI  - [Principles and current possibilities of virtual scenarios for surgery planning].
AB  - This paper describes several new visualization and interaction techniques that
      enable the use of virtual environments for routine medical purposes. A new volume
      rendering method supports shaded and transparent visualization of medical image
      sequences in real-time with an interactive threshold definition. Based on these
      rendering algorithms a segmentation approach offers intuitive assistance for a
      wide range of requirements in diagnosis and therapy planning. In addition, a
      hierarchical data representation for geometric surface descriptions guarantees
      optimal use of available hardware resources and prevents inaccurate
      visualization. Applications such as virtual endoscopy are described.

PMID- 9931590
TI  - [Virtual operations on real patients].
AB  - The tremendous amount of available medical digital data requires media for
      intuitive information perception. Virtual reality (VR) presents a technique for
      processing the visual data from various diagnostic modalities. From a synthetic
      patient model, the required compact information can be generated. The patient
      model is the basis for planning and processing of surgical procedures.
      Stereoscopically visualized 3-D reconstructions of, for example, tomographic
      scans are used for virtual operations. Today, prototypical tools for the virtual
      training of certain surgical procedures are known. Possible VR applications in
      surgery range from the combination of virtual and real data (augmented reality)
      and intraoperative computer assistance (navigation) to remotely performed
      operations (telerobotics). In particular, the optimization of the man-machine
      interface to integrate VR applications in operating theaters is required.

PMID- 9931591
TI  - [Computer-assisted evaluation of aortic aneurysm morphology for choosing the
      method of therapy].
AB  - Computer aided surgery planning software for AAA is a industry-standard software
      development for viewing patient-specific data on a personal computer through a
      unique approach, which improve visualization, navigation, and decision support
      capabilities for both open and endovascular surgery. Raw scan data is extracted
      from CT scans, and rendered into a three-dimensional format. This 3D modeling
      technology and user interface provides a patient-specific model with a rapid
      visual access to the full range of information, including accurate 3D assessment
      of AAA morphology and pathology, interactive multiplanar reconstructions,
      measurements, and views to assist the surgeon in understanding of complex 3D
      relationships. It provides an optimal system for patient evaluation and selection
      for endovascular repair of AAA and in the post-operative evaluation of stent
      deployment and/or complications, such as endoleaks.

PMID- 9931592
TI  - [Thoracoscopic management of fractures of the thoracic and lumbar spine].
AB  - In 90 patients, stabilization of injuries of the thoracic spine and the
      thoracolumbar junction was performed using minimally invasive thoracoscopy. The
      method includes partial corporectomy with spinal decompression, interposition of
      a tricortical bone graft, and anterior spondylodesis by planting. Complications
      were rare and not severe, with only two conversions to open technique. Compared
      to the open, standard method benefits included reduced postoperative pain,
      shorter hospital stay and reduced morbidity.

PMID- 9931593
TI  - [Minimally invasive adrenalectomy--comparison of surgical approaches].
AB  - Nowadays, minimal invasive operating technique are an essential part of adrenal
      gland surgery. Meanwhile four different methods are being used: laparoscopically
      in the supine or lateral position or retroperitoneoscopically as a prone or
      lateral method. Until now, it is not evident whether laparoscopy or
      retroperitoneoscopy should be preferred. Laparoscopy offers a familiar anatomical
      exposure but requires 4-6 trocars. For the retroperitoneoscopic methods only
      three trocars are needed, whereas orientation in the operating field is more
      difficult. All endoscopic procedures to the adrenal gland demand high surgical
      skills. They require expended experience in minimal invasive surgery as well as
      special knowledge in endocrine surgery.

PMID- 9931594
TI  - [Diagnosis of non-palpable testis: value of a new miniaturized laparoscope].
AB  - Laparoscopy and magnetic resonance imaging (MRI) are competitive tools in the
      diagnosis of nonpalpable testis. We investigated 29 boys for this indication with
      MRI. If MRI failed to locate the testis, laparoscopy was performed with a new,
      miniaturized set of pediatric instruments (1.9-mm optic). MRI revealed 10
      inguinal and 7 abdominal testes. There was no false-positive finding. In 12 boys
      MRI showed no testis. Four cases were true negative, 8 false negative (32%). In
      these 8 MRI-negative patients, laparoscopy revealed 7 inguinal and 1 abdominal
      testis. The optical quality of the mini-telescope was sufficient for a 100%
      correct diagnosis. Laparoscopy-related complications did not occur. In summary,
      laparoscopic evaluation is the preferred method in pediatric cases of nonpalpable
      testes.

PMID- 9931595
TI  - [Laparoscopy in the newborn infant--indications and procedure].
AB  - The indications and technical features of minimal invasive surgery, which is of
      particular interest in neonates, are being discussed. Thirty-three laparoscopies
      had been performed as of 1997. The youngest child was 2 days old; the smallest
      one weighted 2150 g. The most frequent indications were clarification of
      cholestasis, cystic masses, pyloromyotomies and sigmoid resections. Three
      conversions were necessary (two choledochal cysts, splenic torsion).
      Complications were one postoperative incisional hernia and two rectal stenoses
      after sigmoid resection. CONCLUSION: Laparoscopy can even be performed in
      newborns and meets the requirements of minimally invasive surgery.

PMID- 9931597
TI  - [Responsibilities of the surgeon for therapy planning in solid tumors].
AB  - Surgery is still the primary domain for patients suffering from solid cancers,
      although in many cases multimodal treatment will be required. If the surgeons
      want to retain this status, the interdisciplinary dialogue must be intensified,
      as treatment strategies are developed today in an interdisciplinary context.
      There is a unique chance for future surgeons to establish and lead "tumor boards"
      within their infrastructure. Tumor boards should be built up in almost every
      hospital to deal with surgical oncology throughout the entire country. If
      necessary, specialists from other hospitals or cancer centers must be involved,
      and modern information technology such as telecommunications should be used to
      obtain second opinions. Using this technique, smaller hospitals in the area can
      adapt to the progress and standards of dedicated cancer centers. Modern
      techniques of telecommunication allow for case presentations and discussions on
      treatment strategies over long distances, as well as virtual teleconferences in
      tumor boards meetings. The future role of surgeons in the treatment of solid
      cancers will depend largely on their ability to resolve the problems outlined
      here. The surgeon himself must become the modulatory core factor within this
      evolutionary process.

PMID- 9931598
TI  - [Bone metastases--stabilization as the goal].

PMID- 9931596
TI  - [Laparoscopy in suspected Crohn disease in childhood].
AB  - The traditional diagnostic tools for the diagnosis of Crohn's disease barely
      reach the terminal ileum. For coloileoscopy in children, anesthesia is required.
      We have used it for an additional and simultaneous laparoscopy, including
      biopsies from lymph nodes or the liver. In 11 children (mean age 11.8 years)
      laparoscopies were performed in order to establish the diagnosis Crohn's disease.
      In 9 children laparoscopy was performed simultaneously with coloileoscopy. A 5-mm
      laparoscope was advanced through the umbilicus and a 1.7-mm forceps through the
      left lower anterior abdominal wall. There were no complications. Laparoscopy
      provides a novel, direct image of the early stages of Crohn's disease and may
      initiate a more adequate medical treatment.

PMID- 9931599
TI  - [Lung metastases: tumor reduction as an oncologic concept].
AB  - The principle of surgery for lung metastases is the removal of all lesions in the
      lung that are either visible or detectable by palpation. This may be combined
      with complete dissection of all ipsilateral lymph nodes. Therefore, "tumor
      reduction" rather than "complete" or "radical resection" may be an adequate
      description of this surgical approach. Since the dissemination of-
      macroscopically not detectable--tumor cells represents the major mannerism of
      every metastatic disease, any local therapy appears to be a discrepancy. However,
      in most cases the rationale of surgery for lung metastases is the lack of
      effective systemic therapy and the low morbidity of surgery, along with up to 60%
      5-year survival rates.

PMID- 9931601
TI  - [Ulcerative colitis, duration of conservative therapy and surgical sequelae].
AB  - Ulcerative colitis can be cured by surgery, and the question of how long
      conservative therapy should be maintained can be easily answered. It should last
      as long as there is no indication for surgery. In cases of a colitis-associated
      cancer, the indication is already the presence of low-grade dysplasia. Rectal
      cancer can be resected and reconstructed with an ileoanal pouch in UICC I and II
      down to 3 cm from the dentate line. In cecal tumors lymphadenectomy should be
      performed under preservation of the ileocolic artery. As for refractory colitis
      an active course of more than 2-4 episodes per year should not be tolerated and
      permanently active colitis for no more than 6 months. Surgery is also indicated
      in emergencies with intractable bleeding after a transfusion of more than 4 units
      of blood and in toxic courses after therapy-resistance for more than 48 h.

PMID- 9931600
TI  - [Resection of liver metastases--possibilities for a cure].
AB  - Retrospective analysis of 167 liver resections in patients with liver metastases
      of colorectal carcinoma revealed the following prognostic factors: UICC stage of
      the colorectal carcinoma (stage I/II vs III/IV), number of liver metastases (1-3
      vs > 3 metastases), size of liver metastases (< or = 5 cm vs > 5 cm). Most
      important for long-term survival was the curative (R0) resection with a
      histologically proven tumor-free resection margin of more than 1 cm (P = 0.0496).
      Simultaneous resection of liver metastases and the primary colorectal carcinoma
      did not influence lethality and morbidity or long-term survival.

PMID- 9931602
TI  - [Complications related to surgery in ulcerative colitis, pouchitis, special
      sequelae--internal medicine viewpoint].
AB  - There are indications that pouchitis after ileal pouch-anal anastomosis is a
      remanifestation of the underlying disease--ulcerative colitis--under different
      conditions. A small group (approximately 5-10% of the patients) develops chronic
      severe pouchitis with total villus atrophy. It has recently been shown that even
      high-grade dysplastic epithelial changes and DNA aneuploidy occur in chronic
      pouchitis. Thus, surveillance programs might be necessary for these patients.
      Pouchitis is a clinical model to study the pathogenesis of chronic destructive
      mucosal inflammation systematically.

PMID- 9931604
TI  - [Colonic diverticulitis--therapy concepts from the surgical viewpoint].
AB  - Colon diverticulitis showed a great variability in kind, intensity and course of
      disease. Time and surgical procedure are dependent on the stage of diverticulitis
      (emergency procedure, elective resection, early elective resection). In emergency
      cases non-resecting procedures should not be performed. Here the Hartmann
      procedure and in favorable conditions the primary resection should be chosen.
      Other patients with acute diverticulitis should have early elective resection
      after short-term medical treatment (5-7 days). Patients with a chronic-recurrent
      course of disease should have an elective one-sided resection. The surgical
      principles are mobilization of the splenic flexure as well as the widening of the
      distal resection limit into the upper rectum to avoid a recurrence.

PMID- 9931603
TI  - [Crohn disease--principle of longitudinal therapy planning with early surgical
      indications].
AB  - Because of its unknown etiology the treatment of Crohn's disease is of a
      symptomatic nature. Therapeutic decisions mostly revolve around hour one can
      obtain the best quality of life for the patient. An active inflammatory flare-up
      is normally treated with steroids; there is no known remission maintenance
      therapy thereafter. In all other cases a surgical treatment option has to be
      considered, in particular with steroid dependency, refractory disease and the
      presence of complications. Deficiencies after surgery must be assessed. 5
      Aminosalicylic acid helps in maintaining postoperative remission maintenance.

PMID- 9931605
TI  - [Diagnosis of diverticulitis in routine practice: progress due to pelvic CT?].
AB  - In a retrospective study 243 pelvic CTs in patients with acute sigmoid
      diverticulitis and elective resections were analyzed. A statistical correlation
      of radiological and histological findings was performed. The sensitivity of the
      CT in diagnosing sigmoid diverticulitis was 97.5%; the overall accuracy of the
      pelvic CT was 97.1% in acute diverticulitis. For the contrast enema the
      sensitivity was 71.6% and the accuracy rate ranked 71.3%. The pelvic CT in
      patients with clinical suspicion of acute sigmoid diverticulities is well suited
      for a primary diagnostic tool and can precisely show the extraluminary extension
      of the inflammation.

PMID- 9931606
TI  - [Primary delayed indication for single-step continence resection in 300 patients
      with acute colonic diverticulitis].
AB  - Since 1980, a total of 300 patients with colonic diverticulitis have undergone
      surgery. A vital indication forced us to do an emergency colostomy or Hartmann
      procedure in 22 cases. Except for 3 patients, the indication for resection was
      intentionally delayed by means of conservative treatment and a primary
      anastomosis was performed. Histological findings verified an inflammatory tumor,
      and abscess, a fistula or perforation in 50% and circumscript inflammation in
      37%. The main complications were drainage problems (infection/retention of
      secretion, n = 18) and anastomosis insufficiency (n = 5), lethality was less than
      2%. In general, we think that multistep surgery is not mandatory--even in
      advanced cases.

PMID- 9931607
TI  - [Risk and benefits of pancreas transplantation].
AB  - Because of exocrine secretions of the gland, pancreas transplantation carries its
      own specific risks. Perioperative morbidity is significantly higher than after
      isolated kidney transplantation. The incidence, however, has been greatly reduced
      the last few years. The patient survival rate and graft function rate are
      excellent. By drainage of the graft into the small bowel and venous connection
      with the portal system, an almost completely physiological status can be
      restored. The effect on diabetic late complications vastly depends on the extent
      of damage induced by the long-standing diabetes mellitus. Physical capacity and
      quality of life increase dramatically in almost all patients after a successful
      pancreas transplantation. Thus, almost all patients urgently request
      retransplantation when the graft is lost.

PMID- 9931608
TI  - Kupffer cell-dependent reperfusion injury in liver transplantation: new
      clinically relevant use of glycine.
AB  - Kupffer cell-dependent reperfusion injury occurs to the liver following
      transplantation, most often in fatty livers which fail most frequently due to
      primary nonfunction. Failure was largely blocked with Carolina rinse solution,
      which contains glycine, and prevents the activation of Kupffer cells.
      Furthermore, gentle in situ organ manipulation, which cannot be prevented using
      standard harvesting techniques, has a detrimental effect on survival. These
      effects were also prevented by glycine. Since proteolytic activity is increased
      in both fatty and manipulated livers, amino acids were measured in rinse
      effluents collected at harvest. A combination of four amino acids correlated with
      graft function. It is concluded that glycine could be beneficial in clinical
      liver transplantation to prevent reperfusion injury, and that amino acids
      measured at harvest may predict graft function.

PMID- 9931609
TI  - [Increasing organ donation by regionalization].
AB  - According to the German transplantation law all hospital are obliged to report
      potential donors. This obligation can only become effective with comprehensive
      support provided by an organ procurement organization. Together with additional
      tasks, e.g., in the field of information and motivation, the entire service
      requires a financial basis which is only available in a region of a certain
      minimum size, minimum activity and minimum reimbursement, respectively. The
      regionalization of organ donation has to be considered independently from
      questions of allocation.

PMID- 9931610
TI  - [Fair distribution in transplantation medicine].
AB  - Organ allocation according to medical criteria is unjust, incoherent and violates
      the autonomy of donors. Those who are not willing to donate do not act unjustly.
      However, those who allocate an organ to a person who is not willing to donate,
      while a person who has been willing to serve as a donor is left untreated, act
      unjustly. Respecting the autonomy of a potential donor to such an extent that
      organs may not be explanted even though this may cause the death of another
      person implies that the wish not to donate to those refusing to donate
      themselves, should be respected as well.

PMID- 9931611
TI  - [Geographical differences of thyroid carcinoma and basic molecular principles].
AB  - Geographical differences have been demonstrated for the cancer incidence and
      histology of differentiated thyroid cancer. Iodine intake and specific external
      noxes, such as nitrosamine ingestion or external radiation are important factors.
      It is still questionable whether histologically identical differentiated thyroid
      cancers are prognostically different in low and rich iodine areas. Despite
      increased knowledge of molecular and genetic changes in differentiated cancer,
      the present therapy is primarily related to patient age, tumor stage and
      histology.

PMID- 9931613
TI  - [Long-term outcome after surgical treatment of gastroesophageal reflux in infancy
      and childhood].
AB  - In this series 99 out of 131 children have been operated upon gastroeosophageal
      reflux at an age of 2.5 years. They were reevaluated 4.5 years later for their
      longterm results in 1997. All patients have been primary free of reflux
      postoperatively. By questionnaire, x-ray studies and 24 h/ph-metry signs of
      reflux could not be found in 88/99 children. 4 patients proved to suffer from a
      recurrant reflux and 3 out of these had to be reoperated. Another 7 showed a
      mild, not pathological reflux without needing medical treatment. Looking at the
      recurrencies especially preoperative peptic oesophagitis and stenoses as well as
      brachyoesophagus after oesophageal atresia turned out to be a problem in respect
      to prognosis. Control studies for longterm results should be done at least 1 year
      postoperatively.

PMID- 9931612
TI  - [Differentiated thyroid gland carcinoma p-T2/T3--extent of lymphadenectomy].
AB  - Systematic lymphadenectomy, which is compartment-orientated, from central node
      dissection to (modified) radical neck dissection, is not controversial in cases
      with intra-operative macroscopic node involvement. General "prophylactic"
      dissection, at least of the ipsilateral central compartment, is advocated due to
      a high incidence of "occult", microscopic positive nodes, and the elevated risk
      regarding recurrency and survival which is connected to node-positivity, and
      lowered recurrence rates with systematic lymphadenectomy. Nevertheless, the
      biological impact of occult positive nodes, as an independent risk-factor, is not
      yet clear, with important differences between papillary and follicular carcinoma
      ("marker" or "governor" of the disease?). Enhanced operative morbidity by
      extensive lymphadenectomy, especially hypoparathyroidism, must be taken into
      account.

PMID- 9931614
TI  - [Perioperative therapy--possibilities for rationalization].
AB  - The complexity of daily clinical work requires a sophisticated collaboration
      between surgery and anesthesiology, since both departments are interwoven in a
      unique way. This can be accomplished by a rational approach to the following
      topics: clear appointment of areas of competence respecting the principle of
      mutual trust, integration of anesthesiologists in the basic physical examination
      and proposal of case-oriented preoperative diagnostics, agreement on necessary
      preoperative therapy, common consultational meetings for outpatient surgery,
      recovery room availability, instruction of surgical personnel in specific pain
      therapy, availability of co-workers who are competent and willing to cooperate,
      no one-sided renunciation of clinical knowledge, ability or execution, no
      renunication of organizational or structural decision-making and no monopoly on
      perioperative medicine.

PMID- 9931615
TI  - [Endocrine surgery from the viewpoint of the pediatric surgeon].
AB  - The extent of surgery for thyroid tumors is discussed. Prophylactic thyroidectomy
      in MEN II a and b is advocated. Pancreatic surgery is necessary in cases of
      nesidioblastosis, islet cell carcinoma, papillary-cystic neoplasia and
      pancreaticoblastoma. Gastrointestinal tumors with hormonal activity are very
      rare. "Incidental carcinoid" is occasionally found. Early detection of Zollinger
      Ellison syndrome in childhood usually allows for complete removal of a
      gastrinoma. Benign and malignant neoplasms of the adrenals warrant radical
      surgery. We report one case of minimally invasive bilateral removal of the
      adrenals for nodular hyperplasia. Pheochromocytoma in childhood presents several
      peculiarities influencing perioperative management. It may occur as part of MEN
      II a.

PMID- 9931616
TI  - [Chronic inflammatory bowel diseases in pediatric surgery].
AB  - Out of 147 children suffering from Crohn's disease (CD), 34 needed surgery (23%)
      at an age of 12.5 years, usually 4.5 years after conservative treatment. Besides
      acute and planned indications for surgery, the relative indication during puberty
      requires further knowledge of the influence of growth velocity rates for weight
      and height, bone retardation, Tanner stage, chronological age and open epiphysial
      plates. Expecting 2.3 years of postoperative remission, the chance is often
      missed to operate on the prepubertal child at an optimal time leading to growth
      failure, retardation of pubertal development and diminished quality of life.

PMID- 9931617
TI  - [Vena cava invasion in kidney carcinoma--a typical example of multidisciplinary
      surgery].
AB  - Between 1987 and 1998, a total of 79 patients with renal cell carcinoma and venal
      caval thrombus underwent radical nephrectomy with removal of the tumor thrombus.
      Of these patients, nine had atrial thrombus extension. Actuarial 5 year survival
      for patients without metastasis was 39%. For patients with tumor thrombi not
      invading the right atrium (state I-III) the 5 year survival rate was up to 50%
      and was not related to the cranial extent of the tumor thrombus. We conclude that
      an aggressive multispeciality surgical approach is justified as it provides
      prolonged survival even in patients with large vena caval thrombi.

PMID- 9931618
TI  - [Surgical therapy of tumor embolism of the vena cava in renal cell carcinoma].
AB  - Radical nephrectomy (Nx) with vena caval thrombectomy represents the only
      realistic chance of cure for patients with renal cell carcinoma with extension
      into the vena cava inferior (VCI). For stage III, with tumor extension in the
      retrohepatic VCI up to the diaphragm, a venous bypass technique is described.
      From July, 1996 through April, 1998, Nx combined with thrombectomy of the VCI was
      performed by isolation of the VCI, temporary occlusion of the hepatoduodenal
      ligament, and temporary extracorporal femoral-axillary veno-venous bypass with
      the Biomedicus pump. Radical resection of tumor thrombus from the VCI was
      accomplished under direct vision with minimal blood loss and without
      cardiopulmonary complications. With a follow-up of 21, 16, 9, 2, and 1 months,
      respectively, all patients are so far free of complications and without recurrent
      or metastatic disease.

PMID- 9931619
TI  - [Pelvic exenteration from the surgical viewpoint].
AB  - Pelvic exenteration (PE) is associated with specific problems in the indication
      of excision and reconstructive surgery. Indication are colorectal cancer or
      cervical cancer recurrence. In each case intensive and early cooperation of
      gynecologist, surgeon and urologist is warranted. Thus, PE is indicated in some
      T3 N1 and T4 rectal carcinoma patients without distant metastases and may be
      superior to chemotherapy. In cervix carcinoma recurrence, PE with or without
      intestinal reconstruction is of specific importance. While intestinal
      reconstruction may improve the quality of life in R0 resected patients we
      reluctantly perform this in noncurative treated patients, since their expected
      survival time is limited and reconstructive surgery in these pretreated patients
      (radiation and surgery) increases the risk of morbidity.

PMID- 9931620
TI  - [Rectal resection within the scope of multi-visceral interdisciplinary resection
      in the pelvis].
AB  - Multivisceral resectioning is the only curative treatment for progressive
      carcinomas extending beyond the organ. The results of 25 consecutively operated
      patients are presented in this prospective observational study. Twelve patients
      underwent surgery for a primary tumor and 13 for a recurrence. Radical
      resectioning was achieved in 5 of 12 and in 3 of 13 patients. Restoration of
      continuity obtained in 11 of 12 and in 7 of 13 patients. Morbidity was 33% and
      62%. None of the patients died from complications. An aggressive surgical
      approach is justifiable on account of the acceptable morbidity and mortality as
      well as the high rate of preserved continence through modern reconstruction
      procedures.

PMID- 9931621
TI  - [Progress in diagnostic imaging of the thorax (CT, MRI, intervention)-
      significance and value for the surgeon].
AB  - Among radiological diagnostical procedures, the conventional chest X-ray has
      retained its significance as a screening investigation up to the present. Digital
      imaging does not reveal any advantages. Due to its higher resolution the CT scan,
      particularly the spiral CT scan, has markedly increased radiological
      possibilities, thus influencing surgical oncology significantly. Tumor invasion
      of the mediastinum, heart, and thoracic wall has become detectable, as well as
      enlarged lymph nodes and metastases. CT angiography permits a better assessment
      of large vessels by aortic rupture or dissection and pulmonary embolism, to name
      a few. MRI is inferior to CT scan in this respect, displaying a slight advantage
      in terms of detecting tumor infiltration of the nerval plexus, i.e. pancoast
      syndrome.

PMID- 9931622
TI  - [Role of 18F-FDG positron emission tomography in surgical evaluation].
AB  - Positron emission tomography (PET) using F-18-fluorine-deoxy-glucose (FDG) as a
      metabolic marker is a non-invasive diagnostic tool that can distinguish malignant
      processes from normal tissue by means of increased glycolysis. Since the advent
      of whole-body scanning, its higher spatial resolution compared with conventional
      scintigraphic methods leads to widespread applications of FDG-PET in oncology.
      The clinical value of FDG-PET has been proven for a number of tumor entities. As
      will be shown in the following review for bronchial, colorectal and pancreatic
      malignomas, functional imaging with FDG-PET provides relevant diagnostic
      information complementary to morphologic imaging.

PMID- 9931623
TI  - [Significance and value for the surgeon--the role of surgical examination.
      Endosonography within the scope of colon and rectal surgery].
AB  - Because of its accuracy rate, flexible rectal endosonography is a standard
      examination in the preoperative staging of rectal tumors, especially for uT3
      tumors. Assessment of regional lymph node involvement is not as accurate as that
      of tumor invasion depth. The overstaging is caused by the presence of reactive
      swollen lymph nodes. Causes of understaging of lymph node status included the
      presence of metastasis solely in the extramesorectal node. The surgical strategy
      depends on the endosonographic tumor stage: EUS T1 N0 G1: local transanal
      resection; EUS T2: anterior resection, EUS T3: preoperative radiochemotherapy.
      After preoperative radiochemotherapy no understaging of local tumor infiltration
      was observed. Numerous errors in rectal cancer staging by endosonography are
      possible.

PMID- 9931624
TI  - [Progress in diagnostic imaging in the area of the pancreas (CT, MRI, MR-angio,
      hydro-CT, MR cholangiopancreatography)].
AB  - Advances in diagnostic pancreas imaging concern the MRCP and SCT. Both methods
      must be performed with the best possible strategy. For MRCP, this means the oral
      application of a superparamagnetic contrast medium and the i.v. injection of
      SekretolinR. The SCT requires a two-phase technique with sufficient contrast
      medium and flow after bolus tracking. It is to be expected that MRCP will replace
      diagnostic ERCP. Although the results of MRI are similar to SCT, it still cannot
      replace this method due to the considerable costs and long examination times. The
      diagnostical procedure has to be applied prior to possible stent implantation to
      avoid artifacts caused by the manipulation.

PMID- 9931626
TI  - [Esophageal carcinoma: guidelines in surgical therapy].
AB  - According to oncological criteria, resections for esophageal cancer require a
      combined abdominal and thoracic approach and should include two-field
      lymphadenectomy. The value of a three-field lymphadenectomy is still under
      discussion, because this extended lymph node dissection may provide better
      survival rates for patients with proximal esophageal cancer and positive lymph
      node stages on the one hand, but will cause increased morbidity, on the other. A
      neoadjuvant radio- and/or chemotherapy allows down staging in about 50% of
      patients with advanced esophageal cancer (stage IIB, III or IV). This leads to
      higher resectability rates, but is not necessarily associated with better
      survival rates.

PMID- 9931625
TI  - [Esophageal carcinoma. Staging and necessary preoperative diagnosis].
AB  - The routine examination in esophageal carcinoma includes the following
      established recommendations: endoscopy with biopsy--X-ray of the esophagus-
      endosonography--cervico-thoraco-abdominal CT scan--bronchoscopy in tumors of the
      upper half of the esophagus. Diagnostic laparoscopy is gaining increasing
      importance, especially with regard to the distal adenocarcinoma of the esophagus.
      Other new diagnostic tools directly influencing clinical practice are magnetic
      resonance tomography, positron emission tomography and possibly the detection of
      circulating or bone marrow tumor cells.

PMID- 9931627
TI  - [Esophagus carcinoma--systemic or local risk of recurrence--which perioperative
      measures are successful?].
AB  - In patients with locally advanced esophageal cancer, a complete tumor resection
      is usually not possible. We report an interim analysis of an ongoing phase II
      trial with multimodal therapy. From February 1995 to November 1997, 50 patients,
      median age 54.9 years, with uT3N0/N + M0 tumors of the suprabifurcal esophagus,
      staged by endoscopy, EUS, and CT scan had neoadjuvant, simultaneous
      radiochemotherapy (RTx/CTx): total dose 30 Gy und 300 mg 5-FU m2 day1 continuous
      infusion. Surgery was performed 35 days after RTx/CTx. 43/50 (86%) had resection
      after RTx/CTx. Postoperative morbidity was 40%, 30-day mortality after
      reconstruction was 4.7%. Histopathological assessment showed a complete response
      in 3, subtotal in 12, and partial or no response in 28 patients. An R0 resection
      could be achieved in 28/43 (65.2%) patients. The median overall survival was 13.6
      months, after R0 resection 20.6 months vs 9.8 months in R1 resections (p =
      0.001). Complete or subtotal response to RTx/CTx (p = 0.002), complete tumor
      resection after RTx/CTx (p = 0.001) and absence of vascular tumor invasion on
      histopathology (p = 0.0007) were significant prognostic factors. Neoadjuvant
      RTx/CTx, although associated with substantial morbidity, is a promising approach
      for patients with locally advanced esophageal cancer located at or above the
      tracheal bifurcation in responding patients, provided an R0 resection can be
      achieved.

PMID- 9931628
TI  - [Barrett carcinoma as a tumor entity with special therapy consequences].
AB  - The development of columnar lined epithelium with intestinal metaplasia in the
      distal esophagus is a possible, but not a necessary, end stage of advanced
      gastroesophageal reflux disease. Currently, research is focused on the
      carcinogenesis of Barrett's carcinoma and the metaplasia-dysplasia carcinoma
      sequence, since it is a malignoma with the highest increasing incidence in
      Western industrial countries. Possible causes of the above-mentioned sequence are
      excessive acid, duodenogastric reflux, and genetic factors. A curative surgical
      approach is the radical R-0 resection. Some centers prefer the transmediastinal
      esophagectomy. Others prefer the transthoracic en bloc esophagectomy.
      Reconstruction can be done with the stomach and the colon. Patients with advanced
      disease probably benefit best from multimodal therapy with neoadjuvant
      radiochemotherapy.

PMID- 9931629
TI  - [Obligatory and facultative measures in diagnosis and staging of stomach
      carcinoma].
AB  - A differential therapeutic regimen in gastric cancer requires exact staging.
      Criteria for accurate staging include exact localization of the tumor, the tumor
      depth, as well as the definition of local spread (lymph node metastases) and
      distant metastases (liver metastases, peritoneal carcinosis). Endoscopy,
      endoscopic ultrasound (EUS), laparoscopy and laparoscopic ultrasound provide the
      most precise information concerning T-, N- and M-categories in preoperative
      staging.

PMID- 9931630
TI  - [Barrett and stomach carcinoma: surgical guidelines].
AB  - The aim of surgical therapy of adenocarcinoma in Barrett's esophagus and gastric
      carcinoma is an R0 resection of the infiltrated organ including regional
      lymphadenectomy. In Barrett's carcinoma these requirements can be achieved by
      radical transhiatal subtotal esophagectomy and lymphadenectomy of the lower
      mediastinum and compartment I and II. In case of adenocarcinoma of the thoracic
      esophagus, a transthoracic en bloc esophagectomy is indicated because of the
      probability of mediastinal lymph node metastasis. In gastric cancer the criteria
      for the luminal extent of resection are localization, depths of infiltration, and
      histological type according to Lauren. In carcinoma of the antrum of intestinal
      type and stage T1, T2 (T3) and in distal T1-carcinoma of diffuse type a subtotal
      gastric resection is possible. All other carcinomas require total gastrectomy
      which, in case of infiltration of the cardia, should be extended to the distal
      esophagus. A local excision of gastric carcinoma in curative intention can only
      be performed in mucosal carcinoma (pT1a) of intestinal type. As several studies
      have shown an improvement of prognosis by D2-lymphadenectomy, especially in UICC
      Stages II and IIIa, a D2 lymphadenectomy is suggested in order to achieve, aside
      from a better staging, a possible prognostic gain for special subgroups of
      patients with beginning lymph-node metastasis. Principle splenectomy in case of
      gastrectomy increases morbidity and is more disadvantageous concerning prognosis.
      Therefore, splenectomy only is suggested in case of proximal gastric carcinoma
      because of the special type of lymph-node metastasis.

PMID- 9931631
TI  - [Hypothetical and reliable aspects of pre-, intra- and postoperative adjuvant
      therapy of stomach carcinoma].
AB  - The results of surgical therapy of gastric cancer could not be improved in recent
      years. Therefore, different perioperative modalities were investigated for this
      tumor. A series of studies could not show any survival benefit using
      postoperative adjuvant radio- or chemotherapy after complete resection of the
      tumor. Data available about preoperative chemotherapy in locally advanced tumor
      stages may demonstrate an increased R0-resection rate after objective remission
      resulting in a prolonged survival compared to surgery alone. Furthermore, in
      others trials intraoperative radiation or intraperitoneal chemotherapy could
      decrease the incidence of locoregional recurrence or peritoneal carcinomatosis
      and improve the overall survival rate. These treatment modalities, above all
      preoperative chemotherapy, must be proven in precisely defined patient
      populations within prospective trials to achieve clearcut data in the future.

PMID- 9931633
TI  - [A critical analysis of different outcomes in surgery of colon carcinoma].
AB  - Five-year survival rates following colon carcinoma surgery are influenced by (1)
      type of survival rate calculation (observed, adjusted or cancer-related, relative
      or age-corrected), (2) definition of carcinoma (inclusion of Tis or high grade
      dysplasia?), (3) distribution of proven prognostic factors, in particular R,
      pTNM, grading and surgeon, and (4) carefulness of histopathologic tumor
      classification. The impact of the surgeon, i.e. the quality of surgery, is now
      proven by multivariate analysis. In adjuvant treatment studies, quality assurance
      of surgery and pathology is indispensable.

PMID- 9931632
TI  - [Basic molecular biology of colon and rectal carcinoma--when differential
      diagnosis?].
AB  - Colorectal cancer (CRC) is one of the most common cancers in Western populations,
      striking both women and men at approximately equal rates. A genetic basis for the
      development of cancer has already been suggested by Karl Heinrich Bauer in 1928
      but only since the advancement of molecular biology direct evidence has been
      obtained to support the notion that cancer is a genetic disease. Recent progress
      in our understanding of the molecular basis of the most prevalent colorectal
      cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and
      familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis
      and therapy. Identification of genetic risk factors for the development of
      adenomas and associated carcinomas of the colon and rectum results in predictive
      molecular diagnosis of malignant disease and enables preventive treatment.

PMID- 9931634
TI  - [Multi-visceral resection in colorectal carcinoma].
AB  - Report of 173 patients with colorectal carcinoma, who were submitted to a
      multivisceral resection. After curative operation a histologically proven
      infiltration of neighbouring organs could be seen in 55% of cases, whereas in the
      other patients only inflammatory adhesions were identified. Postoperative
      surgical complications were observed in 11.4% and were identical with the level
      of complications in conventionally operated patients. Also comparable were the
      postoperative mortality rates (3.6%/3.4%). The 5-year survival rate of all
      multiviscerally resected patients was 42%, after curative resection 51%. The UICC
      stage related survival rates were 58% and 43% in stage II and III, versus 60% and
      41% after conventional resection. The identical operative risk and identical
      survival rates justify the application of multivisceral resection in the
      treatment of colorectal carcinoma.

PMID- 9931635
TI  - [Anterior rectum resection and abdominoperineal rectum excision: guidelines for
      decision making].
AB  - Carcinomae of the upper third of the rectum are, almost without exception, and
      without loss of continence, resectable. The diagnosis of an intact sphincter
      function is significant in the pre-operative phase, when deciding whether to
      carry out an anterior rectum resection or an abdominoperineal rectum
      exstirpation. Concerning tumours as from G3 in the middle and distal thirds, a
      safety margin of at least 5 cm distal must be kept, thus making an anterior
      resection impossible. Stage IV tumours whose growth has infiltrated neighbouring
      organs or the pelvic wall are also not suitable for resection. Should anatomical
      circumstances such as excessive adipositae, very large carcinomae, narrow pelvis
      and enlargement of the uterus or prostata prevent the safe dissection of the
      mesorectum a sphincter-retaining operation is also not indicated. Oncologic
      safety is of the highest priority when considering such cases.

PMID- 9931636
TI  - [Extended resection of locally advanced primary and recurrent rectal carcinomas
      by interdisciplinary cooperation of various surgical specialties].
AB  - Multivisceral resections have been performed on 35 patients with primary and 45
      with recurrent rectal cancer. Lethality was 3.7%, morbidity was 9%. Macroscopic
      adhesions were confirmed histologically as tumorous in 66% of the additionally
      resected organs. Tumor invasion, tumor recurrence and surgical radicality were
      found as statistically significant prognostic factors. In radically resected
      primary tumors 5-yr-survival was 49%. Multivisceral resection in rectal cancer is
      possible with low morbidity and lethality and potentially curative in primary
      tumors. In recurrent tumors multivisceral resections are frequently palliative.

PMID- 9931637
TI  - [Primary liver and bile duct tumors: approach to conservative therapy].
AB  - In case of non-resectable primary liver cancer the following treatment modalities
      can be applied: ligation, embolization or balloon occlusion of the hepatic
      artery, locoregional chemotherapy, percutaneous ethanol or acetic acid injection,
      microwave application, and cryotherapy, as well as combined therapeutic
      modalities. The 3-year survival rates for patients with small hepatocellular
      carcinomas (HCCs) are comparable for the different procedures (resection, ethanol
      or acetic acid injection, cryotherapy, microwave application) and range between
      60-80%. In patients with larger HCCs the prognosis seems to be improved by a
      combination treatment of chemoembolization and ethanol injection compared to
      chemoembolization alone.

PMID- 9931638
TI  - [Operation or intervention in advanced gallbladder carcinoma?].
AB  - In a retrospective study of patients with locally advanced or metastatic
      gallbladder cancer, we tried to define patient groups, that profit either from
      extended resection, palliative surgery or intervention. 102 out of 160 operative
      treated patients (73.8%) had UICC-tumor stages III and IV. Depending on the T
      stage, resection rates were 31% for T3-stage and 12.5% for T4-stage tumors.
      Corresponding median survival times were 20.2 and 18.1 month, respectively.
      Patients with T3/T4-tumor stages, where only palliative surgery was possible, had
      median survival times of 2.5 to 4.5 month. So, only radical tumor resection can
      result in better survival times and should be performed even in elderly patients
      in good condition. Palliative surgery does not improve survival and, moreover,
      often not life quality.

PMID- 9931639
TI  - [What is the risk of resection of the right hepatic artery in resection of
      central bile duct carcinoma?].
AB  - Between 1990 and 1994 we performed tumor resection on 21 patients with a
      cholangiocarcinoma of the porta hepatic. In 5 cases a segmental
      resection/ligature of the patent right hepatic artery was performed. The
      postoperative course of recovery in these 5 patients was compared to that of the
      other 16 patients. We found no significant differences in either the
      postoperative course of recovery or the laboratory parameters of the two groups.
      There was no clinical liver necrosis or bile duct necrosis (which would have
      manifested itself as a leak in the anastomosis) in either group. On the basis of
      our experience, segmental resection/ligature of the right hepatic artery as part
      of a radical cholangiocarcinoma resection is possible provided that the right
      portal vein is patent.

PMID- 9931641
TI  - [Classification of neuroendocrine tumors and the effect on surgical technique].
AB  - Neuroendocrine tumors of the gastrointestinal tract are heterogenous regarding
      hormone production and tumor biology and have a varying disease course and
      survival time. In 1995 Capella et al. proposed a new classification of
      neuroendocrine tumors combining characteristics of the primary (i.e. histological
      differentiation, size, extension into surrounding tissues, hormonal activity and
      angioinvasion) and its suspected biological behavior (benign, uncertain, low
      grade malignant, high-grade malignant). The extent of surgical therapy depends on
      the malignant potential of the primary tumor. To evaluate the usefulness of this
      classification in practical work neuroendocrine tumors have to be categorized by
      this classification and these data have to be correlated with the individual long
      term course of patients.

PMID- 9931640
TI  - [Gastrointestinal stroma tumors--a special entity with unique radicality
      principles].
AB  - Gastrointestinal stromal tumors (GIST) are rare. Their malignant variety
      represents only 3 percent of all malignant GI tumors. These tumors are most
      frequently found in the stomach and in the small bowel, while tumors of the large
      bowel are rare. Notably in the rectum slightly more tumors are found, easy access
      possibly enhancing diagnosis of asymptomatic lesions. Preoperatively and
      intraoperatively it is difficult to distinguish benign and malignant lesions.
      Treatment requires complete removal with a two centimeter margin. Systematic
      lymphadenectomy is not required. Tumor grading has been determined as prognostic
      factor for malignant GIST. Overall 5 year survival following potentially curative
      resection was 69 percent in our series of 46 patients.

PMID- 9931642
TI  - [Characteristics of anal carcinoma with therapeutic consequences].
AB  - Anal cancers have to be looked at either as cancers of the anal canal or those of
      the anal margin. During the past years, evidence has been obtained that human
      papilloma virus (HPV) contributes to the formation of cancers, particularly in
      homo-sexual males. Surgical treatment alone, may only be considered in tumors
      with less than 2 cm in size. Combined radio-chemotherapy (RCT) using 45 Gy of RT
      + 5-FU/Mitomycin C is the treatment of choice with superiority to RT alone proven
      in randomized trials. Abdominoperineal excision is indicated only in case of a
      tumor recurrence or with stable disease or progression after RCT. Multimodal
      treatment after discussion in an experienced tumor board may result in recurrence
      free and colostomy-free survival at 5 years in up to 80% of our patients.

PMID- 9931643
TI  - [Primary liposarcomas of the mediastinum].
AB  - Primary liposarcomas of the mediastinum are rare neoplasms comprising less than
      1% of mediastinal tumors. While in early stages often asymptomatic they may grow
      to an enormous size and then exhibit various clinical symptoms mimicking lung or
      heart disease by compression of adjacent intrathoracic organs. Intention of
      surgical treatment is to relieve the symptoms and to establish the histological
      diagnosis. Surgery alone may be curative in some cases. The role of additional
      radio- and chemotherapy remains questionable. We report two cases of primary
      mediastinal liposarcomas that were treated surgically in our institution.

PMID- 9931644
TI  - [Stereotactic tumor biopsy and tumor excision].
AB  - Stereotactic procedures are indicated in nonpalpable breast lesions that are
      suspicious in mammography. Using the ABBI system all established procedures
      (stereotactic needle biopsy, fine needle biopsy, core needle biopsy) can be
      performed. Also the resection of cylindrical tissue specimen with a maximum
      diameter of 20 mm can be carried out, controlled by digital mammography. For the
      exact diagnosis of lesions with a diameter up to 15 mm, cylindrical extirpation
      is recommended. In several cases this can be considered as definitive lumpectomy.
      Neither lesions localized close to the thoracic wall nor retromamillary lesions
      can be treated by using the ABBI system. While digital mammography is the method
      of choice for the detection of microcalcifications, the visualization of
      opacifications may be difficult. Overall the ABBI system was used in 40.7% of our
      patients with nonpalpable breast lesions.

PMID- 9931645
TI  - [Initial experiences with the Advanced Breast Biopsy Instrumentation (ABBI), a
      system for stereotactic excision of non-palpable breast lesions].
AB  - The advanced breast biopsy instrumentation (ABBI) allows the radiologically
      guided stereotactic excision of non-palpable radiodense lesions with high
      accuracy. Forty-six patients with suspicious clusters of microcalcifications (n =
      37) and with round lesions (n = 9) of the breast were investigated using the
      ABBI. Tissue cylinders were successfully removed in 98% of cases. No wound
      complications occurred and cosmesis was excellent. Histopathology revealed 35
      benign (76%) and 11 malignant (24%) lesions. With the ABBI system, non-palpable
      breast lesions can be precisely localized and excised.

PMID- 9931646
TI  - [Sentinel node detection in breast carcinoma].
AB  - Sentinel node (SN) detection is a reliable method to detect lymph node metastases
      in breast cancer patients. While blue dye allows to follow the lympatic stream
      towards the sentinel node the use of radioactive marked protein allows a
      preoperative identification of the SN (e.g. internal mammary artery). Detection
      rate and predictive value depend on the tumor size, tumors of a diameter greater
      than 30 mm show a poor detection rate and a lower predictive value. With regard
      of the increased rate of detected micrometastases the SN principle has a higher
      predictive value for the nodal status then the axillary clearance. Since no long
      term results are available yet the advantage for the patients remain unclear.

PMID- 9931647
TI  - [Surgery of extensive retroperitoneal soft tissue sarcoma].
AB  - For retroperitoneal soft-tissue tumours the only treatment capable of having an
      impact on the course of the disease still is complete surgical resection.
      Therefore, the pre- and intraoperative assessment of resectability is of
      particular interest. MRT imaging has gained importance for preoperative imaging.
      Distant metastases and infiltration of non-resectable vascular or neural
      structures preclude resection. In approximately two thirds of patients with
      retroperitoneal soft-tissue tumors complete resection with clear margins (R0
      resection) is feasible. The histological differentiation of the tumor is the most
      important predictor of prognosis following resection. For patients with non
      resectable tumors new adjuvant and neo-adjuvant treatments are currently being
      reconsidered in an EORTC trial.

PMID- 9931648
TI  - [What is the value of recent molecular biology knowledge for surgical oncologic
      therapy of soft tissue sarcoma?].
AB  - While clinical progress in the treatment of soft-tissue sarcoma is rather slow,
      some major contributions to the understanding of oncogenesis of these rare tumors
      have been achieved in the last decade. The central role of cell cycle regulation
      has been demonstrated in hereditary (p53, RB) and somatic mutations or variant
      expression of genes associated with cell cycle regulation (p53, BCL2, MDM2). For
      a subset of soft tissue sarcomas harboring chromosomal translocations, fusion
      genes resulting from these specific translocations were cloned and characterized.
      The clinical use of these fusion genes may not be restricted to diagnosis and
      prognosis, since these may serve as specific targets for molecular and
      immunologic therapy approaches.

PMID- 9931649
TI  - [Transcutaneous and laparoscopic laser treatment in extensive retroperitoneal
      lymphangiomas in childhood].
AB  - Retroperitoneal lymphangiomas are rare congenital vascular malformations. They
      cannot always be completely excised and are associated with high recurrence,
      complication and morbidity rates. We therefore utilize an alternative treatment
      concept in some cases. We excise the cystic types laparoscopically with a Nd: YAG
      laser (wavelength 1064 nm). Residual tissues are percutaneously managed by
      interstitial laser therapy under MRI monitoring. The high soft-tissue contrast of
      the MRI enables exact positioning of the laser fiber. The examination is
      thermosensitive and provides online and noninvasive demonstration of the
      interstitial tissue coagulation. We have treated four infants laparoscopically
      and three other children percutaneously.

PMID- 9931650
TI  - [Pancreatic carcinoma: conclusive clinical consequences based on molecular
      biology knowledge for therapy].
AB  - Molecular research techniques developed in recent years have increased our
      knowledge of the pathophysiology of pancreatic cancer tremendously. We now know
      that the malignant phenotype of pancreatic cancer is defined by the expression of
      growth stimulatory factors, their receptors and gene alterations. To translate
      molecular knowledge into new clinical therapy will be the challenge of the
      future. Although we have not yet developed direct clinical applications for our
      molecular findings, new diagnostic and therapeutic approaches are in development.
      Gene therapies such as antisense technology, pro-drug activation and the transfer
      of non-functioning growth factor receptors are potential new therapeutic options
      for the future. Wider clinical use can be expected in upcoming years.

PMID- 9931651
TI  - [Pancreatic carcinoma--conclusions and prospects].
AB  - Whereas no progress has been made in the diagnosis of early tumors, the staging
      of pancreatic cancer has improved, mainly through the introduction of ultrafast
      MRI, resulting in a higher resection rate. The early results of standard
      pancreatectomy are now excellent (operative mortality < 2.5%). The late results
      after R0 resections are improving (> 30% 5-year survival), but they are poor
      overall. So far, extended surgical techniques have not brought any improvement
      here. Unfortunately, so far adjuvant radiochemotherapy has not proved effective
      in a recent randomized controlled trial. Molecular and genetic research has
      deepened our understanding of the cancerogenesis of pancreatic cancer without
      leading to clinical consequences so far.

PMID- 9931652
TI  - [Role of protease activation in pathophysiology of acute pancreatitis].
AB  - For over a century it has been assumed that acute pancreatitis represents an
      autodigestion of the pancreas by its own, physiologically inactive proteases.
      Whether, how and where digestive proteases are being activated in the pancreas
      has remained the topic of much controversy and speculation. We review a number of
      recent studies that have been undertaken to elucidate the mechanisms and identify
      the initial subcellular localization of this process. These studies suggest that
      a premature and intrapancreatic protease activation does, indeed, occur early in
      pancreatitis and can be experimentally induced in vivo and in vitro. Activation
      begins within minutes of the induction of pancreatitis and is initially confined
      to cytoplasmic vacuoles at the apical pole of acinar cells. From here trypsin
      activity as well as its activation peptide are transferred to the cytosol of
      acinar cells where autodigestion may begin.

PMID- 9931653
TI  - [Definition of predictors of a complicated course in acute pancreatitis].
AB  - It is of utmost importance to assess the severity of acute pancreatitis
      immediately in order to identify patients with severe or necrotising disease who
      can benefit from early intensive care therapy. Additionally, in face of new
      therapeutic concepts (e.g., antibiotic therapy) and for the evaluation of new
      drugs (e.g. PAF antagonist) patients should be staged as soon as possible into
      mild and severe disease. At hospital admission it is not possible to assess the
      severity on a clinical basis. The "gold standard" up to now has been imaging
      procedures (contrast-enhanced CT and MRI) which should be preserved for the
      severe cases to estimate the extent of pancreatic necrosis. The ideal predictor
      in blood/urine should be objective, reliable, cheap, easy to measure, and
      available every time and should have on hospital admission a high efficacy and
      independence from other diseases. As single factors there are a variety of
      mediators of the "systemic inflammatory response syndrome" which are elevated in
      this disease (C-reactive protein, antiproteases, enzyme activation peptides, PMN
      elastase, complement factors, interleukines and chemokines, etc.). Among all
      these prognostic indicators, C-reactive protein is now the best analyzed
      parameter. However, one should take into account that its highest efficacy is
      reached 3-4 days after onset of disease.

PMID- 9931654
TI  - [Acute pancreatitis: reliable and prospective conservative therapy].
AB  - The management of acute pancreatitis is complex. Although numerous medical
      therapies have been proposed, few interventions have been shown to benefit
      patients with severe disease. Volume resuscitation, total parenteral nutrition
      and an adequate analgesia is the unspecific management of acute pancreatitis.
      Prophylactic antibiotic treatment should be performed in patients with
      necrotizing disease. Selective decontamination of the digestive tract has shown
      beneficial effects only in combination with systemic antibiotic therapy. ERCP and
      endoscopic sphincterotomy should be performed in severe gallstone pancreatitis.
      Somatostatin, protease inhibitors, hemofiltration and peritoneal lavage are some
      of the many medications now proven to be of no efficacy. Two clinical prospective
      trials are now under way to investigate the effects of two promising agents on
      the course of severe necrotizing pancreatitis: lexipafant, a platelet factor
      antagonist, and isovolemic hemodilution with dextran.

PMID- 9931655
TI  - [Pathogenesis of pancreatogenic sepsis].
AB  - The intestinal tract is the motor of sepsis in the "gut-MOF hypothesis". Acute
      pancreatitis causes an early severe reduction of intestinal microcirculation with
      consequent production of radicals and cytokines damaging intestinal integrity.
      The intestinal organ dysfunction syndrome results in a breakdown of barrier
      function and a loss of propulsive activity. This leads to microbial overgrowth
      and bacterial translocation. This liberates cytokines and causes secondary
      pancreatic infection after lymphatic and systemic bacterial dissemination.
      Infected pancreatic necrosis by enteric microorganisms is the main cause of
      pancreatic sepsis.

PMID- 9931656
TI  - [Portal hypertension and variceal bleeding: shunt in concomitant or general
      prehepatic block].
AB  - Thrombosis of the portal system should be ruled out in all patient with
      esophagogastric varices. Such patients with no evidence of concomitant liver
      disease and with a high risk of rebleeding (e.g. gastric varices, low platelet
      counts, endoscopic criteria) should be referred to decompressive shunt surgery.
      The type of shunt is dictated by the patent segments of the portal system.
      Splenectomy should be avoided. The results show a low operative mortality, a zero
      encephalopathy and a low rebleeding rate. Patients with prehepatic thrombosis and
      liver cirrhosis represent a more severe problem since the risk and mortality of
      variceal hemorrhage is high and on the other hand TIPS procedure and liver
      transplantation may be impossible. In case of a high risk of rebleeding or
      endoscopic therapy failure we advocate surgical shunting as the risk of
      encephalopathy appears to be low when portal flow diversion already exists.

PMID- 9931657
TI  - [Effect of a shunt on subsequent liver transplantation].
AB  - Recurrent bleeding from esophageal varices may be prevented by TIPS or surgical
      shunts. Both treatment options bear potential risks for a consecutive liver
      transplantation. TIPS may lead to severe encephalopathy, hepatic functional
      deterioration, shunt occlusion or dislocation. Following surgical shunts,
      technical difficulties during transplantation and portal vene thromboses may be
      encountered. Patients with foreseeable indication for liver transplantation are
      best treated by TIPS. In Child A and stable Child B patients surgical shunts are
      preferable.

PMID- 9931658
TI  - [Indications for restorative rectal resection in carcinoma--complete vs. partial
      and local resection].
AB  - Rectal continence preservation became feasible in treatment of cancer of the
      lower third of the rectum based upon technical evolutions and better
      understanding of tumor biology. Absolutely necessary precondition is correct
      preoperative staging. Operative strategy is determined by tumor stage,
      localization, grade and continence function. In most cases the total mesorectal
      excision leads to tumor-free circumferential resection margins. Distal safety
      margins are assured by intraoperative frozen sections. Restorative approaches are
      contraindicated in case of sphincter infiltration. If continence function is
      impaired preoperatively, restorative procedures lead to a worse functional
      result. The local recurrence remains the most important problem in rectal cancer
      surgery. Safety in resection is achieved by total mesorectal excision. The
      presence of distal satellite metastasis or lymph node metastasis bear a certain
      risk for local recurrence after partial resections of middle or upper third
      rectal cancer. Local resection in T1-Tumors with G1- or G2-Grading may produce
      comparable results.

PMID- 9931659
TI  - [Control of function before and after sphincter-preserving rectal resection].
AB  - Prior to sphincter-saving rectal surgery an in-depth evaluation of the patient's
      anorectal physiology is of paramount importance to avoid poor functional outcome.
      A detailed history comprising all previous operations and childbirths as well as
      a precise proctological examination are the most important steps in the
      diagnostic work-up. A standardized continence score is easy to obtain and can be
      used as a guideline preoperatively as well as during follow-up. Furthermore,
      endosonography, manometric studies and quality of life assessment can add
      valuable information before and after surgery. Electrophysiologic studies are
      generally not necessary and can therefore not be regarded as routine
      investigations.

PMID- 9931660
TI  - [Functional and oncological results of sphincter preserving rectal resection].
AB  - Most of the patients with a carcinoma of the middle and distal third of the
      rectum can now be operated on with a low anerior resection in consideration of
      all aspects of cancer surgery. Our experience with 59 resections with coloanal or
      low colorectal anastomosis was reviewed. The mean distance of the distal edge of
      the tumor to the L. anocutanea was 5.7 +/- 1.9 cm. Within the first 30 days the
      postoperative mortality rate was 3.4% (2/59). The most common postoperative
      complication was urinary retention, which affected 13.5%. The insufficiency rate
      of the anastomosis was 13.5%. Fecal continence was complete in 85% of the
      patients: we observed minor leaks in 6% and major leaks in 9%. Local recurrence
      occurred in 2 cases (3.8%), metastasis was noted in 6 cases (11.3%). Sphincter
      preserving rectal resection is in our opinion an excellent treatment for low
      rectal cancer.

PMID- 9931661
TI  - [Indications for restorative proctocolectomy in systemic colorectal diseases
      (ulcerative colitis and familial adenomatous polyposis coli)].
AB  - Restorative proctocolectomy is now the procedure of choice for patients suffering
      from ulcerative colitis (UC) and familial adenomatous polyposis coli (FAP). The
      majority of patients with UC require surgery for failure or development of side
      effects of medical therapy. Other indications include dysplasia, carcinoma and
      complications from either medical therapy or the disease, such as massive
      bleeding or perforation. In the adolescent patient, resection may be necessary
      owing to growth retardation. In patients with FAP the 100% risk of developing
      colorectal carcinoma can be avoided only by proctocolectomy. Crohn's colitis and
      carcinoma of the lower rectum represent absolute contraindications. A relative
      contraindication exists in indeterminate colitis, patients with poor sphincter
      function, mesenteric desmoids, obesity and an age above 65 years.

PMID- 9931662
TI  - [Complications and late outcome of restorative proctocolectomy].
AB  - The restorative proctocolectomy with ileoanal pouch is a sophisticated operative
      procedure with considerable postoperative complications. The main problems are
      postoperative ileus (11%), anastomotic stricture (9%), local septic complications
      (13%) and pouchitis (29%). A variety of other complications also occur. Most of
      the problems can be successfully managed by conservative or surgical treatment.
      In only 2.5% (n = 15/593) was final pouch extirpation necessary. Postoperative
      function showed elevated stool frequency (6 per day) and slightly compromised
      stool continence. Most patients confirm good quality of life.

PMID- 9931663
TI  - [Complications in children with ulcerative colitis after total colectomy and J
      pouch].
AB  - Our experience with proctocolectomy and the J-pouch procedure in eight children
      with ulcerative colitis is reported. The mean age at diagnosis was 8.4 years, and
      the mean time between diagnosis and colectomy was 2.2 years. We decided on a
      three-stage operation. The protective ileostomy was removed after approximately 4
      months pouch-training. Two patients suffered pouchitis as a specific
      complication. An ileus occurred in two patients, one patient had a serious
      eosinophilic enteritis, and two children had multiple abdominal wall abscesses.
      All patients showed a significant increase in height velocity and the prepubertal
      patients experienced catch-up growth after the colectomy. All patients are
      continent during the day. Our experience suggests that proctocolectomy and the
      ileoanal-J-pouch procedure provide improved growth, continence and a low
      incidence of surgical complications.

PMID- 9931664
TI  - [Insufficiency of the anal sphincter--attempt at anorectal reconstruction].
AB  - Continence is highly appreciated in society and is a precondition for human
      socialization. Thus, in the history of surgery there have been numerous attempts
      to develop repair techniques for incontinence. They can roughly be divided into
      three groups: actively inflatable implants (plastic prosthesis), transfer of
      smooth muscles or transfer of striated, conditioned muscles. In the majority of
      cases these techniques may well prevent the strains associated with colostomy;
      however, the patients will remain incapable of recognizing and discriminating the
      cue of rectal distension. Consequently, repair of sphincter defects will continue
      to be of major concern in surgery.

PMID- 9931665
TI  - [Dynamic gracilis-plasty as final therapeutic possibility in anorectal
      incontinence].
AB  - Six patients (five women, one man with an average age of 63 years) underwent a
      dynamic graciloplasty. Three patients had a three- or two-stage procedure; the
      past three patients were treated by a one-stage procedure without any negative
      consequences. None of the patients received a protective stoma. COMPLICATIONS:
      COMPLICATIONS, needing surgical intervention occurred in two patients. In one of
      these patients a positive final result may still fail. RESULTS: Five patients are
      subjectively continent and satisfied. Four are able to retain a clysma without
      any problem. As a result of stimulation, three patients developed optimal anal
      pressures. In two patients the pressure values are satisfactory. Three patients
      developed evacuation problems, which up to now have been managed by laxatives.
      CONCLUSION: The dynamic graciloplasty is a new hope for carefully chosen
      patients, in whom other methods have failed.

PMID- 9931666
TI  - [Treatment of insufficiency of the anal sphincter by sacral spinal nerve
      stimulation with implantable neurostimulators].
AB  - The feasibility of permanent electrostimulation of the sacral spinal nerves was
      studied in patients with fecal incontinence and no detectable morphological
      lesions and thus not amenable to conventional surgical management. Applying acute
      percutaneous stimulation with needle electrodes, the most relevant sacral spinal
      nerve for striated sphincter muscle function was identified (sacral spinal nerve
      S3 or S4). The therapeutic potential of stimulation was tested by subchronic
      stimulation with temporary wire electrodes and, if effective, permanent
      electrodes were implanted in four patients. Long-term sacral spinal nerve
      stimulation persistently improved anal continence and increased the function of
      the striated muscular anal sphincter.

PMID- 9931667
TI  - [Treatment strategy in pleural mesothelioma].
AB  - The development of diffuse malignant pleural mesothelioma is associated with
      exposure to asbestos. The surgical treatment comprises a radical
      pleuropneumonectomy with resection of the pericardium and diaphragm (P3D) or
      palliative pleurectomy/decortication of the tumor. The prognosis in general is
      poor. P3D is most effective in patients with epithelial mesothelioma at an early
      stage. Complete resection has the best prognosis. Palliative tumor decortication
      is restricted to symptomatic patients with acceptable performance status. The
      prognosis of patients after radical resection is not significantly different from
      patients with pleurectomy/decortication. Preliminary results of multimodal
      therapy concepts, including additional chemo- and/or radiotherapy, suggest an
      improvement in survival. Nevertheless, so far treatment has been focused on the
      palliation of clinical symptoms like pain and dyspnee.

PMID- 9931669
TI  - [Resection of the trachea and bifurcation in newborn infants and children].
AB  - From 1973 to 1994, 38 tracheal and/or bifurcation resections were performed in 37
      children aged 1 month to 18 years. Twenty-four children had an acquired stenosis,
      8 a congenital and 5 a combined stenosis. In 16 children, the stenosis was
      located in the lower trachea or bifurcation. Other malformations were found in 12
      children. The most common intervention was the trachea segment resection in 30
      patients; resection of the cricoid cartilage was performed in another 6 cases.
      The resection was expanded to the bifurcation 5 times, 1 being a left sleeve
      pneumonectomy. The extent of resection was between 10 and 50 mm. In the 22
      children with resections of the upper and middle trachea, 96% were decannulated
      with 0% morbidity. In the 15 children with distal resections, decannulation was
      performed in 87% with 6% morbidity. There were no recurrent stenoses caused by
      growth disorder. With interdisciplinary cooperation, single-session resection is
      a safe procedure.

PMID- 9931668
TI  - [Plastic reconstruction of the irradiated thoracic wall].
AB  - Chest-wall reconstruction following irradiation requires a surgical approach that
      addresses the specific healing disorders associated with irradiation: (1) biopsy
      of any open wound to rule out recurrence or persistence of tumor; (2) aggressive
      debridement of all necrotic or infected tissue, especially osteonecrosis of the
      chest wall; (3) reconstruction with well-vascularized muscle or musculocutaneous
      flaps. Coverage with muscle flaps provides a very reliable and effective single
      stage reconstruction. Most types of flaps employed involve the latissimus, rectus
      abdominis and pectoralis muscle or musculocutaneous flaps. Rarely, stabilization
      of the thoracic wall is required, mostly facilitated by nonresorbable mesh.
      Respecting these principles, the irradiated chest wall can be reconstructed
      safely and with low morbidity. Plastic reconstructive techniques may also be
      employed safely to reconstruct the breast simultaneously in irradiated tissue by
      use of latissimus or rectus abdominis flaps.

PMID- 9931670
TI  - [Carotid surgery--reliable and speculative aspects].
AB  - The current status of endarterectomy in carotid artery stenosis is evaluated in
      prospective randomized studies. The results are very good and high quality.
      Endovascular therapy is in feasibility studies, and the complication rate is too
      high compared with the gold standard endarterectomy.

PMID- 9931671
TI  - [Indications for urgent carotid reconstruction].
AB  - Diagnostic methods and indications for carotid surgery must be coordinated with
      the individual carotid-related stroke risk. The indication for urgent carotid
      reconstruction within a few days after the initial event should always be
      evaluated when a clinical and/or morphological unstable and therefore risky
      carotid lesion is present and the 30-day stroke risk without surgery is > 5%.
      Patients with high-grade symptomatic carotid stenoses fulfill these criteria as
      do patients with recurrent carotid-related TIA, patients with hemipheric TIA,
      patients with symptomatic carotid stenosis and contralateral carotid occlusion
      and patients after a non-disabling carotid-related stroke. The clinical
      significance of sonographic carotid plaque criteria and intracranial emboli
      detected by TCD must be further evaluated in prospective studies.

PMID- 9931672
TI  - [Results of 31 laparoscopic interventions of the aorto-iliac vessels for arterial
      occlusive disease].
AB  - OBJECTIVE: To report our clinical experience with laparoscopic vascular surgery.
      MATERIALS AND METHODS: Since October 1995 we have performed 31 procedures for
      aortoiliac occlusive disease. A transperitoneal approach with pneumoperitoneum is
      preferred. RESULTS: Seven iliofemoral (IFB), 5 aortofemoral (uAFB), 16
      aortobifemoral (AFB) bypasses, two thrombendarterectomies (TEA) of the infrarenal
      aorta, and one obturator bypass were performed totally by laparoscopy. Patients
      experienced a very comfortable postoperative course; all grafts were patent. Five
      conversions to open surgery were necessary because of a severe calcified aorta (n
      = 2), bleeding (n = 1), suture stenosis (n = 1), and fatty retroperitoneum (n =
      1). CONCLUSIONS: Laparoscopic vascular surgery for occlusive disease is feasible,
      safe, and effective. However, further technical and instrumental improvement is
      necessary before the new surgical technique can be recommended.

PMID- 9931674
TI  - [Long-term outcome of distal bypass].
AB  - Although 30 years age reconstructive surgery on crural arteries was technically
      not feasible, primary successful revascularization is now possible in 95% of
      arterial occlusive diseases in the lower leg. If untreated, reocclusion of the
      graft occurs in 40 to 60% during the first postoperative year. With a close,
      morphologically oriented follow-up routine, an assisted primary patency of up to
      80% and an even higher secondary patency can be achieved. Myointimal
      proliferation is mostly responsible for bypass failure in the early postoperative
      period especially at the site of the distal anastomosis.

PMID- 9931673
TI  - [Simultaneous vascular and endovascular surgery of complex vascular diseases].
AB  - Complex vascular disease requires combined, intraoperative endovascular and
      reconstructive therapy. Hereby, transprosthetic, transluminal angioplasty is
      particularly well suited for this purpose. The 5-year patency rate after combined
      inguinal patch plasty and femoral balloon dilation (n = 58) was 70%. The 5-year
      patency rates following transgraft angioplasty, with subsequent stent
      implantation and cross-over bypass (n = 46) and after transprosthetic, popliteal
      crural dilation was 83% and 63%, respectively. Three patients with a type IIb
      (after Allenberg) aneurysm were treated with an aortoiliac stent prosthesis,
      combined with a cross-over bypass. The follow-up examinations at 2, 16 and 36
      months were uneventful.

PMID- 9931675
TI  - [Peripheral prosthesis bypass for saving the extremity].
AB  - We report the results of more than 1000 PTFE tibial bypass implantations during
      the last 20 years. An extra-anatomic lateral bypass to the peroneal or tibial
      artery prevents angulation problems. Using the Linton patch technique, early
      results improved to 85%. In the context of redo-operations long-term results are
      enhanced through the consistent use of PIDDA catheter. In 57% we achieved our
      purpose: limb salvage until the death of the patient or for 3-7 years (3.8 years
      in the middle) at the time of reexamination. Two examples of lateral tibial
      bypasses are given that have been functioning for 18 years.

PMID- 9931676
TI  - [Basic principles and "direct nerve" reconstruction in brachial plexus
      paralysis].
AB  - An exact knowledge of the complex anatomy of the brachial plexus is absolutely
      necessary to carry out this treatment. The most important diagnostic steps are:
      case history, examination, investigation of muscle function and sensitivity,
      myelo-CT, MRI, and neurophysiological investigations. The best time for operative
      revision is between the 6th week and the 3rd month. An individual therapy
      protocol must be established that includes a large spectrum of reconstructive
      options like nerve reconstructions, neurotizations, muscle and tendon
      transposition, muscle transplantation, arthrodesis, orthesis and others.

PMID- 9931677
TI  - [Possibilities for reconstruction in brachial plexus paralysis: neurotization].
AB  - Reinnervation by nerves other than the brachial plexus are necessary if avulsion
      of the roots prevents neural reconstruction of the brachial plexus itself, or if
      functional recovery is unsatisfactory and further reconstruction is necessary for
      improvement. The foreign nerves mostly used today for these neurotizations are
      the accessory nerve, the deep cervical plexus, the intercostal nerves and, more
      and more, the contralateral C7 spinal nerve. Our own experimental studies have
      demonstrated future concepts for reconstructions in very desperate cases to
      improve the final functional outcome in the useless extremity: cross-over
      reinnervation from the contralateral side, end-to-side nerve coaptation, and
      induction of sprouting by offering free muscle transplants to the regenerating
      nerve.

PMID- 9931678
TI  - [Initial muscle operations in brachial plexus paralysis].
AB  - Regeneration after surgical treatment of fresh or delayed brachial plexus
      injuries is often incomplete, with remaining sensory and motor loss. The aim of
      reconstructive surgery for these patients is to regain subordinate motor
      function. Therefore, reconstructive surgery should emphasize the restoration of
      elevation abduction and external rotation of the shoulder, elbow flexion and
      flexion of the fingers for basic grasping.

PMID- 9931679
TI  - [Birth-related brachial plexus paralysis].
AB  - According to the literature, in Europe 0.4-1.2 cases of obstetrical plexus
      brachial paresis occur per 1000 births. A 4-6 times higher energy in axial
      delivery of the newborn leads to a neurotmesis of the plexus. If the energy used
      is more than 10 times higher, root avulsion occur. Early operative therapy for
      obstetrical plexus paresis is mandatory. The best period for an operation is
      between the 3rd and 6th months of age. CT and MRI imaging as well as
      electrophysiological investigations are of the utmost importance. Birch, Gilbert
      and Gu think there is an indication for operation if no active elbow flexion can
      be performed at the age of 6 months. Primary coaptation is easier in babies than
      in adults. However, large defects have to be a bridged by autologous nerve
      grafts. For root avulsions, neurotization with the accessory and phrenic nerves
      (Gu) is being used more and more. In 362 children with 52 operated cases, after a
      follow-up from 2 to 10 years, we found 37 functional, useful recoveries. Nine
      operations were unsatisfactory and two had poor results. In four cases the
      operation was unnecessary.

PMID- 9931681
TI  - [Fracture management during bone growth].
AB  - In treating fractures in children, there have been more and more demands for the
      primary treatment to be definitively planned, i.e., for a conclusive order of
      events to be laid down so as to exclude the necessity for re-reductions or a
      change of therapy. Long-term conservative methods of treatment are becoming less
      and acceptable to parents and children. From the psychosocial point of view, the
      aim must be to avoid extensive periods of hospitalization or bedrest in traction
      and to dispense with repeated anesthesia for re-reduction and changes in
      procedure. The child should be able to leave the hospital as soon as possible
      after a definitive and circumscribed primary course of treatment. Since
      complication-free surgical interventions are now available, many more operative
      procedures for dealing with fractures during the years of growth have become
      routine in this field.

PMID- 9931680
TI  - [Treatment of cartilage defects].
AB  - Articular surface defects will not heal spontaneously. Localized defects, e.g.,
      in the knee joint, should be treated with transplantation of autologous cells
      containing material of different composition. For transplantation of
      osteochondral pegs they are grafted from minor loaded joint areas and implanted
      into highly loaded defect regions. For autologous cartilage cell transplantation
      they are proliferated in vitro and then implanted into the defect zone under an
      periostal flap, harvested from the proximal tibia and sutured into the cartilage
      level around the defect. Autologous paste of cartilage and cancellous bone is
      transplanted into aggressively prepared defects with the concept of regrowing
      articular cartilage out of the transplanted cells and the subchondral bone.

PMID- 9931682
TI  - [Analysis of leg geometry].
AB  - Analysis of bony geometry of the lower limb comprises frontal, sagittal and
      longitudinal alignment, as well as length and torsion, including at first the
      whole leg and finally the femur and tibia separately. Clinical examination
      assesses the bony geometry, functional aspects, ligamentous and soft tissue
      conditions, etc. Frontal and sagittal radiographs indicate axial alignment and
      angles of the hip, knee and upper ankle joint. Apex and size of deformities are
      defined simultaneously. CT and ultrasound techniques allow the measurement of
      length and torsion of the whole leg, as well as of the femur and tibia
      separately, provided those techniques are standardized with proven
      reproducibility.

PMID- 9931683
TI  - [Optimal postoperative nutrition: pro and contra enteral and parenteral feeding].
AB  - Malnutrition is correlated with an increased incidence of postoperative
      complications. As a consequence, preoperative hyperalimentation results in a
      decrease of postoperative complications in patients with malnutrition. In
      contrast, the beneficial effects of postoperative nutritional support are still
      to be proven. The majority of prospective trials have shown limited advantageous
      effects for patients with delayed nutritional intake after the surgical
      procedure. In these patients enteral nutrition has been shown to reduce the rate
      of infectious complications. If enteral nutrition cannot be applied, the addition
      of glutamine as a dipeptide is beneficial with regard to intestinal barrier
      function.

PMID- 9931684
TI  - [Relevance of preoperative nutritional therapy for postoperative outcome].
AB  - Several studies on preoperative artificial nutrition have shown beneficial
      effects only in severely malnourished patients (weight loss > 15% within short
      time, serum albumin < 2.8 g/dl). In this group of patients undergoing major
      gastrointestinal surgery, the postoperative complication rate was reduced to 40
      60%. The medical care costs saved per complication avoided were 11,000-14,000 US
      dollars. A 5-day period of preoperative oral application of immunonutrition
      containing omega 3-fatty acids, arginine and nucleotides at home may prevent the
      risks of preoperative hospitalization and may lead to immunomodulating effects,
      which in addition to the improvement of nutritional status, will be able to
      decrease postoperative complication rates by a further 50-60%.

PMID- 9931685
TI  - [Pancreatitis and translocation--approaches for nutritional strategies].
AB  - Translocation of intestinal bacteria from the gut into pancreatic necrosis is an
      important factor in the development of septic complications in acute
      pancreatitis. Bacterial translocation is promoted by an impaired intestinal
      mucosal barrier, which can be attributed to the reduced oxygen and substrate
      supply of the intestine. A rat model of severe acute pancreatitis has been used
      to confirm the hypothesis that an impaired mucosal barrier can be stabilized by
      supplying certain nutrients, vitamins, and trace elements. A reduction in
      secondary pancreas infections with intestinal bacteria and improved survival was
      achieved under intravenous glutamine substitution, an essential amino acids in
      stress situations for enterocytes, colonocytes and immunocompetent cells. The
      positive experimental results are currently being investigated in a controlled
      randomized multicenter trial. Comparable studies need to be performed for
      verifying the effect of other nutritive factors on bacterial translocation and
      the disease course in acute pancreatitis.

PMID- 9931686
TI  - [Development of an immuno-neutral lipid emulsion for optimal postoperative
      management of intensive care patients].
AB  - Lipid emulsions prolong the rejection of allogeneic rat heart grafts in relation
      to their n-3 to n-6 fatty acid ratio. Because of the predominance of n-6 fatty
      acids soybean oil, which is clinically applied, shows an immunosuppressive
      effect. An n-3 to n-6 fatty acid ratio of 1 to 2 proved to be immunoneutral.
      Intravenous fat emulsions with an impaired n-3 to n-6 fatty acid ratio reduce
      cytokine release, infiltration and proliferation of immunocompetent cells. Lipids
      rich in n-3 fatty acids additionally reduce the release of the potent
      vasoconstrictor thromboxane A3 and increase the synthesis of leukotriene B5,
      which unlike leukotriene B4 does not activate polymorphonuclear neutrophils.
      Based on our results, the production of a clinically applicable lipid emulsion
      with a n-3 to n-6 fatty acid ratio of 1 to 2 can be recommended for the optimal
      parenteral nutrition of ICU patients with a markedly reduced immune system.

PMID- 9931687
TI  - [Effect of alanyl-glutamine in postoperative total parenteral nutrition on
      postoperative immunosuppression and morbidity. Preliminary results of a
      prospective randomized study].
AB  - The impact of glutamine substitution on postoperative immunosuppression and
      morbidity was investigated in patients with surgical interventions and total
      parenteral nutrition in a prospective randomized trial. To analyze immune
      competence, the expression of CD3, CD4, and CD8 on lymphocytes and of HLA-DR and
      CD14 on monocytes as well as the plasma levels of IL-6 and IL-10 was evaluated
      before, 1, 2, 4, and 7 days after surgery. A total of 34 patients have been
      included (with glutamine: n = 18; without glutamine: n = 16). Patients with
      glutamine substitution showed decreased systemic inflammation, significant faster
      compensation for postoperative immunosuppression and a lower incidence of
      postoperative complications. Patients without postoperative complications showed
      no significant differences in postoperative immunosuppression.

PMID- 9931688
TI  - [Treatment of an infected focus, considerations and facts on duration of
      antibiotic therapy].
AB  - Contamination does not require postoperative antibiotics, as the infective source
      is dealt with operatively. In "resectable infections" (appendicitis) a
      postoperative antimicrobial 24-h course should be administered. We have to grade
      infections according to their severity. Even established peritonitis does not
      require postoperative antibiotic administration for more than 5 days. "Severe"
      infections (infected pancreatic necrosis, peritonitis with planned
      relaparotomies) require more than 5 days of antibiotic therapy.

PMID- 9931689
TI  - [Special therapeutic approaches for interrupting the cascade--from systemic
      inflammatory response syndrome to multiple organ failure].
AB  - SIRS, sepsis and MOF are clinical sequelae related to persistent, uncontrolled
      inflammation. Therefore, different strategies for treatment were designed to
      block the cascade from SIRS to MOF (anti-inflammatory therapies). However,
      clinical trials using these agents have failed to demonstrate any benefit. In
      sepsis the body also mounts an anti-inflammatory response, which has been largely
      ignored. If the anti-inflammatory reaction is sufficiently severe, we might
      increase the susceptibility to infection or even exacerbate immunosuppression by
      using anti-inflammatory agents. In contrast, agents to stimulate the immune
      system--like IFN-gamma or G-SCF--may prove beneficial.

PMID- 9931690
TI  - [Colorectal surgery--an integral part of general surgery!].
AB  - The controversy, whether colorectal surgery should be performed by the general
      surgeon or the specialist colorectal surgeon, is gaining increasing importance in
      Europe. The short and long term results in colorectal surgery as well as in other
      subspecialties are largely determined by the annual case load and the surgical
      training in colorectal surgery. If both conditions are met, colorectal surgery
      can be just as safely and successfully performed in a district hospital by a
      general surgeon. The following advantages support the treatment of colorectal
      lesions by a general surgeon: the capacity to cope with unforeseen intraoperative
      problems thanks to the broad surgical experience of the general surgeon, the
      ability and authorisation to perform multivisceral resections and the ability
      through the daily training in abdominal surgery to perform emergency
      interventions since about 30% of all colorectal operations are performed in an
      emergency setting. Against colorectal specialisation can be argued: increased
      costs through the need of specialised colorectal surgeons, the establishment of
      independent units for colorectal surgery, impairment of surgical training and
      sometimes loss of enthusiasm through the daily routine of the highly specialised
      surgeon. The common colorectal surgery should remain an integral part of general
      surgery, given the conditions of an sufficient annual case load of at least 30
      colorectal resections and of an adequate surgical training in colorectal surgery.

PMID- 9931691
TI  - [Pathophysiology of nerve compression].
AB  - Pathophysiology of nerve compression is related to the pathology and mechanical
      factors of intraneural vessels. Compression increases the permeability with
      subsequent intrafascicular edema formation and changes in nerve blood flow. The
      deterioration of intraneural blood flow induces epineural and perineural
      thickening with impairment of nerve conduction. Later axonal lesions causing
      sensory and motor deficiencies occur.

PMID- 9931693
TI  - [Ulnar nerve compression in the area of the wrist].
AB  - Clinical investigation precisely determines the localization of ulnar nerve
      entrapment in Guyon's canal. The cause of compression can be due to internal
      (tumor, distal fibrous arch or proximal ligament arcade, nerve or muscle
      anomalies) or external influences (ulnar neuropathy of cyclists, thrombosis of
      ulnar artery by hypothenar hammer syndrome, fractures of pisiform or hook of
      hamate). Treatment involves splitting the roof of Guyon's canal, the ligaments or
      muscle anomalies, and excision of a tumor.

PMID- 9931692
TI  - [Nerve compression in the lateral neck triangle].
AB  - Among the compression neuropathies associated with the lateral cervical neck
      region the thoracic outlet syndrome has received special attention during the
      last decades. In resistant cases, the transaxillary decompression of the
      neurovascular bundle according to Roos proved to be very successful for us. Since
      1982, a total of 185 procedures of this kind were performed with the following
      results: excellent and good 76%, fair 16%, and not successful 8%.--As the
      symptoms of Sudeck's dystrophy resemble the clinical findings of a severe
      thoracic outlet and inlet syndrome, a transaxillary decompression together with
      sympathectomy was performed in nine resistant dystrophies as well. Thus, in seven
      patients an excellent result was obtained, and a good and a fair result in one
      case each. According to our findings, the individual predisposition for Sudeck's
      dystrophy is based on an impairment of the venous run-off due to a stenosis of
      the subclavian vein with simultaneous increase of sympathetic activity.

PMID- 9931694
TI  - [Repeat interventions after decompression of the carpal tunnel].
AB  - If after carpal tunnel release, symptoms continue or progress, or if new ones
      appear, they must be examined thoroughly and differentiated. Such symptoms may
      hint at incomplete splitting of the retinaculum flexorum, a more proximally
      located nerve compression (faulty diagnosis or double-crush syndrome), a general
      or a new disease, a previously unrecognized or a new hypertrophic synovialitis, a
      hypertrophically contracted scar, or a neuroma. Iatrogenic lesions have
      frequently been reported. A second follow-up operation is indicated only after
      all findings, including the neurophysiological assessment, have been taken into
      consideration: scar, neuroma resection, revision and neurolysis of the median
      nerve at all levels. The most difficult question is the coverage of the nerve in
      the scar tissue with thin and well-vascularised tissue. Various types of flaps
      using muscle or subcutaneous or synovial tissue have been suggested.

PMID- 9931695
TI  - [The problem of interactions in perioperative prophylaxis: reducing the risk or
      increasing the risk?].
AB  - Risk research and risk analysis have to be modeled as a fairly complex system
      including multivariate regression modeling for risk factors in etiology, Markov
      models in pathogenesis, and a construct of mechanistic and hermeneutic variables
      for clinical outcome analysis. The McPeek index is proposed as an example.
      Several prophylaxes for risk reduction in the perioperative period produce risk
      reduction as well as risk augmentation in different types of outcome. These
      unexpected findings were observed not only in clinical trials, but also in animal
      experiments and in isolated tissues. This demonstrates a basic problem of
      handling complexity in the real clinical setting.

PMID- 9931696
TI  - [Effect of the mortality and morbidity conference on clinical success and
      clinical atmosphere].
AB  - Mortality and morbidity (M and M) conferences have been presented in surgical
      departments in Anglo-Saxon countries for decades. In Germany, only few
      institutions provide a regular M + M conference. M + M conferences are part of
      the quality assessment within a department and follow the theory of continuous
      improvement. After describing a deficit in patient care, the reasons for this
      deficit are analyzed to avoid such a recurrence in the future. M + M conferences
      discuss only a minor number of complications occurring in a department compared
      to a prospective complications registry using a computerized data base. On the
      other hand, an open discussion during a M + M conference provides a good academic
      atmosphere within a department.

PMID- 9931697
TI  - [Additional qualifications in "special pain therapy"--an advantage to surgeons as
      well?].
AB  - Deficits in the treatment of patients with chronic pain lead the German
      Parliament of Physicians (Deutscher Arztetag) in 1996 to adapt a special
      curriculum called "Special Pain Treatment". Objectives and contents are defined
      in detail in guidelines accepted from 10 out of 17 federal commissions in Germany
      at this time. Because transitional regulations have been administered until now,
      surgeons have not yet been required to obtain the qualification. The prescribed
      curriculum and particularly the contract between the association of general
      practitioners and the insurance companies make the acquisition of the
      qualification and the permission to use it in private practice covered by
      insurance very difficult for surgeons.

PMID- 9931698
TI  - [Recommendations and guidelines for perioperative pain therapy in Germany].
AB  - The management of perioperative and post-traumatic pain in clinical practice is
      still significantly deficient in Germany as shown in a recently published
      representative and anonymous survey of 1,000 surgical clinics. Several steps were
      undertaken to improve the situation: in 1992, an agreement on responsibilities
      and organization was achieved between the "Berufsverbande" of German Surgeons and
      of Anaesthesiologists. In 1997, recommendations on the treatment of perioperative
      and post-traumatic pain were published by the two "Berufsverbande" together with
      the Scientific Societies of Surgeons and Anaesthesiologists. In 1998, national
      guidelines based on consensus methods in collaboration with the Association of
      the Scientific Medical Societies in Germany (AWMF) will be published at the
      Internet address http://www.uni-duesseldorf.de/WWW/AWMF/.

PMID- 9931699
TI  - [Efficacy of an Acute Pain Service--a controlled comparative study of hospitals].
AB  - The efficacy of an acute pain service was prospectively evaluated on elective
      abdominal operations by comparing two surgical departments including a total of
      498 patients. The patients of the clinic with an acute pain service reported less
      pain (at rest and in movement) pre- and postoperatively and received more
      analgetics. They had more appetite, lower sleep requirements and more
      independence. The patients' overall satisfaction was greater in the clinic with
      an acute pain service.

PMID- 9931700
TI  - [Molecular biology contributions to wound healing and practical applications].
AB  - Keratinocyte growth factor (KGF) is a potent mitogen for keratinocytes which is
      strongly expressed at the wound edge after skin injury. Inhibition of KGF
      receptor signalling in the epidermis of transgenic mice caused a delay in wound
      reepithelialization. To determine the mechanisms of KGF action in keratinocytes,
      we searched for genes which are regulated by KGF. One of these genes codes for
      activin which we identified as a novel important player in the repair process.
      Furthermore, expression of a novel peroxidase was induced by KGF. The expression
      pattern of this enzyme during wound repair suggests that it could protect
      keratinocytes from reactive oxygen species during the early inflammatory phase.
      Taken together, our studies provide new insights into the mechanisms of action of
      growth factors during the healing process.

PMID- 9931702
TI  - [Local surgical measures in chronic wounds].
AB  - The treatment of chronic wounds is initiated by resection of gangrenous tissue,
      drainage of abscess formations, and--if necessary--primary resection of necrotic
      bone and joint structures in the phalanxes. The restoration of arterial blood
      perfusion in the periphery is a central part of wound management. Several
      surgical procedures such as necrosectomy, topical application of antiseptic
      solutions, and hydrocolloid wound dressings serve to create well-vascularized
      granulative tissue. The application of vacuum occlusive dressings promotes the
      proliferation of fibroblasts that result in a dense granulative tissue. In the
      majority of cases, wound closure can be performed by suture traction or with the
      help of autologous skin grafts.

PMID- 9931701
TI  - [Biological wound tissue glue systems in wound healing].
AB  - Tissue engineering relies on in vitro cell culture, biocompatible matrix
      materials and genetic engineering with growth and differentiation factors for
      guided tissue regeneration. Biogenic or semisynthetic biomaterials are an
      alternative as cell carriers: To circumvent the disadvantages of conventional
      keratinocyte sheet grafts, a keratinocyte fibrin glue suspension KFGS (H. W.
      Kaiser et al., Burns 20: 23, 1994), which mainly consists of epidermal stem
      cells, has been tested experimentally in nude mice and clinically in extensive
      burns and chronic wounds. In the "in vivo culture" on the wound, the non
      confluent keratinocytes form a differentiated epithelium within days. Current
      research aims at guided dermal regeneration by a combination with allodermis or
      biomaterials (collagen sponges like TissueFaszie, Microspheres etc.). Fibrin glue
      (Tissuecol) has also been tested successfully as matrix for other cells like
      chondrocytes and fibroblasts transfected with growth factor genes (EGF/KGF).

PMID- 9931703
TI  - [Effect of dressing materials on wound healing].
AB  - In the early 1970s, a major revolution in the management of wounds began. Simple
      woven absorbents that kept the wound as dry as possible were superseded by
      occlusive dressings that provided moist wound healing. The wound healing process
      is influenced by control of moisture content, thermal properties, gaseous
      permeability, pH effects, and impermeability to micro-organisms. Low adherence of
      the dressing provides protection of the newly formed tissue and relieves the
      patient's pain during removal.

PMID- 9931704
TI  - [Interdisciplinary treatment concepts in chronic wounds].
AB  - Interdisciplinary concepts for the treatment of chronic wounds are mandatory
      because of the multifactorial reasons causing ulceration. This is a report on 6
      years' experience at the wound care unit in Tubingen. Patients with chronic
      wounds (mainly diabetic, venous, and ischemic ulcers) were treated primarily as
      outpatients according to a standardised and interdisciplinary wound care
      protocol. Quality control was guaranteed by a standardised wound documentation
      system. The evaluation of this data demonstrates an overall healing rate of 69%
      within 52 weeks (mean). Before patients were referred to Tubingen, unsuccessful
      therapy was characterised by a mean wound duration of 35 weeks. The results
      presented justify this interdisciplinary wound care unit.

PMID- 9931705
TI  - Typical experiences of a former research fellow in the USA.
AB  - Besides personal experience as a former research fellow, the prerequisites for a
      successful research fellowship in the USA were analysed. Individual initiatives
      without any infrastructure for successful reintegration at home will fail.
      Isolated publications will carry the insignia of the guest university without
      providing benefit for the home institution at a later stage. The ideal
      constellation is the continuity of international cooperation in combination with
      an active research group at home. In addition to the respective publications, the
      following achievements of a research period in the USA can be attained:
      Establishing ongoing contacts to an international research group in the own field
      of interest; training in "how to write a scientific paper"; introduction to the
      "international scientific community". The potential contact to other groups
      cannot be planned, but represents an important aspect of a research period. To
      learn to appreciate other peoples' way of living adds to the personality of every
      scientist.

PMID- 9931706
TI  - [The common surgical heritage].
AB  - The mutual and dreadful history of Poland and Germany has left behind wounds and
      scars on both sides. This session is dedicated to the common surgical heritage
      and joint development of the presence and future. Important pioneering
      contributions of German surgery were achieved at the University of Breslau
      (Wroclaw), especially by Johann von Mikulicz-Radecki and his associate Ferdinand
      Sauerbruch. Our Polish colleagues have further developed the surgical tradition
      in Poland since World War II.

PMID- 9931707
TI  - [Development and importance of surgical oncology in Germany].
AB  - Karl Heinrich Bauer (1890-1978) must be considered the Nestor of surgical
      oncology in Germany (mutation hypothesis 1928, monograph "Das Krebsproblem" 1949,
      German Cancer Research Institution (DKFZ) in Heidelberg 1964). The biological
      understanding of tumor disease has influenced the standardization of surgical
      procedures and has integrated these into a multimodal oncological concept,
      including neoadjuvant and adjuvant radio- and chemotherapy. Guidelines and
      consensus recommendations for the diagnosis and treatment of solid tumors have
      been established. Laparoscopic oncological surgery is under discussion and should
      be restricted to prospective trials.

PMID- 9931708
TI  - The prospective multicenter trial of gastric cancer.

PMID- 9931710
TI  - [The concept of "microsurgical" technique in medullary thyroid carcinoma].
AB  - Medullary thyroid carcinomas (MTC) metastasize early into the regional lymph
      nodes. Calcitonin is a highly specific and sensitive marker for these tumors,
      which is feasible for follow-up and for screening. Additionally, in families with
      hereditary MTC the responsible mutations of the RET-proto-oncogene can be
      identified, and prophylactic surgery can be provided. We operated on 127 patients
      for MTC, 114 of whom had diagnosed carcinomas; 13 operations were performed with
      prophylactic intention. A total of 101 patients needed microsurgical dissection
      of the cervical compartments. Of these, 31% could be cured, and a further 46%
      showed postoperatively normalized basal calcitonin concentrations. Thirteen
      patients who needed mediastinal dissection had persistent increased levels of
      pentagastrin-stimulated or basal calcitonin values. All patients who underwent
      prophylactic surgery could be cured.

PMID- 9931709
TI  - [The German EORTC Study of neoadjuvant therapy of stomach carcinoma].
AB  - The improvement of the prognosis of gastric cancer after neoadjuvant therapy was
      shown in a phase II study with etoposide, adriamycin and cisplatinum (EAP). Due
      to high-grade toxicity with EAP, the verification of this therapeutic concept in
      a randomized phase III study with a less toxic regimen had to be demonstrated in
      a second phase II study. A combination with cisplatinum, leucovorin and 5-FU in
      comparison to EAP was less toxic, but clinical response after chemotherapy was
      shown to be identical. Of 41 patients, 36 patients underwent surgery with a R0
      resection rate of 73.2% (n = 26). After a median follow-up of 18.3 months, 23
      patients with R0 resection were alive, 19 patients (73%) showed no evidence of
      recurrent disease. There was no major morbidity and no postoperative mortality
      observed. Thus, chemotherapy with cisplatinum, 5-FU and leucovorin seems to be
      suitable for a randomized multicenter trial sponsored by the EORTC. For entrance
      into the study the following requirements should be met: prospective diagnostic
      procedures including endoscopic ultrasound (EUS) and surgical laparoscopy;
      standardised surgery (gastrectomy with D2-lymphadenectomy): prospective
      histopathological work up of the resected specimen including ypTNM category,
      ypUICC stages and R classification; prospectively scheduled follow-up intervals.
      Aim of the study, including 198 patients per treatment arm with a recruitment of
      3 years and a minimum follow-up of 2 years, is the verification of the positive
      prognostic impact of neoadjuvant chemotherapy followed by surgery compared with
      surgery alone in locally advanced gastric cancer (cuT 3cN1-3cM0).

PMID- 9931711
TI  - [Der Chirurg and Langenbecks Archiv fur Chirurgie--2 different directions by
      surgical publications].
AB  - DER CHIRURG is the most successful German surgical journal and, reaches with a
      circulation of more than 8400 copies approx. 60% (including secondary readers
      approx. 80%) of active surgeons in Germany. DER CHIRURG covers scientific
      information by highly qualified reviews (30%-35% of the content) as well as peer
      reviewed original papers (60%). The rejection rate of original papers is
      currently 55%. Topics of the reviews are as follows: oncology (20%), benign
      gastrointestinal surgery (20%), traumatology (15%) and general topics (20%). The
      thematic spectrum of the original papers is similar. The current problems for
      this journal are quality control, the issue of double publication, the assurance
      of an adequate impact factor, and the recruitment of local and international
      experts for highly qualified reviews.

PMID- 9931712
TI  - [Guidelines and recommendations for a successful congress abstract].
AB  - The title and introduction of the abstract must clarify the intention of the
      study. The methods part must define the study and control groups and the
      statistical methods of comparison. In the results part, the data must be
      presented clearly, possibly in tables or graphs, interpretations must be strictly
      omitted. The text and the tables must not be redundant. The part discussion
      and/or conclusions may have the greatest variability. It is important, however,
      that the data presented support the interpretation and conclusion. And last but
      not least: the promise of too many additional studies may be unrealistic.

PMID- 9931713
TI  - [Position of the German Society of Surgery in the community of scientific
      specialty societies].
AB  - The role of the German Surgical Society among the other scientific societies is
      considered as well as its relationship to the BAK and its scientific activities
      and publications compared with internal medicine. Its most important current
      issues are described and explained. It can be shown that it holds a prominent
      position, but is scientifically less productive than internal medicine.

PMID- 9931714
TI  - [Promotion of research in surgery by the Swiss National Foundation].
AB  - The Biology and Medicine division of the Swiss National Science Foundation
      finances about 1200 research projects. Only 24 (2%) of them originate from
      surgical departments or clinics. If we look at amounts, the share is even
      smaller, namely, 1.4%. Compared with the fields a pure "Medical Research Council"
      would cover, the share is 3.5% or 2.8% for the number of the amount,
      respectively. The problems of surgical research are only one special case of the
      problems in clinical research in Switzerland. Our new TANDEM program should
      encourage better collaboration between researchers in basic biological sciences
      and those in clinical medicine.

PMID- 9931715
TI  - [Promoting research in Germany].
AB  - The DFG is the major funding organisation for research at German universities. A
      considerable amount of funds are spent on clinical research, including surgical
      research. Despite some success, the quality of clinical research in Germany is
      not considered to be satisfactory. Where are the deficits, and how is it possible
      to improve the situation? By which mechanisms could the DFG add to the
      improvement of clinical research?

PMID- 9931716
TI  - [Classification of surgical interventions in Germany].
AB  - Today different classification systems are used in Germany for the
      standardization and coding of surgical procedures. On January 1, 1995, the German
      Minister of Health introduced a new classification system called
      "Operationenschlussel nach section 301 SGB V" (OPS-301) for surgical procedures
      performed in hospitals. The standardization by the OPS-301 is limited to
      inpatients. In outpatient care, surgical procedures are coded by two billing
      systems: EBM and GOA. Thus, the situation is characterized by coding systems that
      are used in parallel which are to some extent incompatible. This leads to
      avoidable workload and lower quality of the documented data. The general goal is
      the development of a new classification system which on the one hand should be
      able to provide different views depending on the questions. On the other hand the
      system should integrate the different views through a clear and consistent
      structure of surgical procedures.

PMID- 9931717
TI  - [OPS-301/ICPM: experiences and problems].
AB  - For over 2 years, the classification of procedures OPS-301 has been uniformly
      used in all German hospitals. The ICPM in German extension has 5-6 digits and is
      totally compatible with the OPS-301 restricted to operations. This ICPM is
      qualified for scientific documentation beyond efficiency control. The OPS-301
      needs some better representation and some extensions proposed by medical experts.
      A program that searches for invalid code numbers and uses the relations of OPS
      301 to sex, age, and department in a knowledge base, detects a 10% error rate in
      manual coding with OPS-301. A coding program reduces them to 1.4%. After mapping
      the OPS-301 by SNOMED this monohierarchical classification becomes
      multihierarchical. This is advantageous for coding and retrieval.

PMID- 9931718
TI  - [European pre-standard: structure of classification and coding of surgical
      procedures].
AB  - The European Prestandard "Medical Informatics--Structure for Classification and
      Coding of Surgical Procedures" was worked out by Working Group II "Terminology,
      Sematics and Knowledge Bases" of CEN/TC 251 in 1995. It was the purpose of this
      prestandard to provide the conceptual structure of a surgical procedure
      description. In this way the standard can support the exchange of surgical
      procedure information between different national classifications and languages
      within Europe. The standard comprises the concept types with modifiers, governed
      by a list of combinational rules and a diagram which summarises the concept
      system. Examples are given to explain the structure. Other concept fields
      relating to surgical procedures are discussed. Application of the prestandard
      both for the maintenance of procedure classifications and as the conceptual model
      in the GALEN Project are explained.

PMID- 9931719
TI  - [Procedure Coding System: background and development].
AB  - In the USA, the ICD-10 Procedure Coding System (ICD-10-PCS) was developed because
      the current system ICD-9-CM Vol. 3 did not allow new technologies to be
      incorporated as new codes. PCS is a seven-digit muliaxial coding system which
      covers a broad spectrum of surgical and nonsurgical procedures. Its structure is
      easily understood and guarantees sufficient expandibility. Background and
      structure of PCS are presented with examples from surgical sections and discussed
      in comparison with ICPM.

PMID- 9931720
TI  - [Procedure Coding System (PCS): evaluation by the Ministry of Health].
AB  - It can be assumed that the German surgical procedure coding system OPS-301 must
      be replaced by a new coding system at the beginning of the next millennium. The
      "Procedure Coding System (ICD-10-PCS)" which is presently being developed in the
      USA was considered the most promising system by the German Curators for questions
      of classification in Public Health (KKG). Therefore, a working group with members
      representing all organisations of the KKG was established to evaluate the PCS
      with special reference to the German conditions. The working group found that PCS
      is at the moment the best available procedure coding system. The German version
      of PCS has been licensed by DIMDI in December 1997 and will therefore be in the
      public domain. The German version will be developed in co-operation with all
      involved organisations for pilot studies and accompanying scientific evaluation,
      thus a maximum of consensus should be achieved.

PMID- 9931722
TI  - [Legal aspects of prevention of thrombosis].

PMID- 9931721
TI  - [Medical principles of thromboembolism prevention].
AB  - Since thromboembolic complications have been described to be one of the most
      frequent complications following surgery, a correct indication for prophylaxis is
      of great clinical importance. This requires comprehensive knowledge about the
      general thrombosis risk of various patient populations, experience in the
      assessment of the individual thrombosis risk, understanding of the mode of action
      of various prophylaxis modalities, and critical benefit/risk assessment when
      pharmacological agents are used. Patients with a moderate or high risk require
      medical prophylaxis with either unfractionated heparin, low molecular weight
      heparins, or oral anticoagulants unless there is too high a risk of bleeding.
      Mechanical methods such as physical exercise and early mobilisation of the
      patient remain the basic measurements which can be supplemented by graduated
      pressure stockings.

PMID- 9931723
TI  - [Intensive care medicine from the viewpoint of patients, their family and nursing
      personnel].
AB  - We wanted to know how our intensive care unit would be graded by the patients,
      their family members and the staff, as well as the impression that intensive care
      medicine made on them. A total of 82% of the patients and 90% of the family
      members were of the opinion that they owed their lives to intensive care
      medicine, and 100% of the patients and 96% of family members deemed intensive
      care medicine significant. The patients and their family members judged the
      medical and nursing care, the medical technology, the care of basic needs and
      their accommodation altogether positive. The nursing staff held a contrary
      opinion and were more critical. Competent explanation and transmission of
      information represented the most important factor in forming a positive opinion
      of intensive care medicine.

PMID- 9931724
TI  - [Is graduate education for surgical specialist adequate? Results of a survey of
      surgical assistants in Berlin-Brandenburg].
AB  - A questionnaire was sent to all surgical registrars in Berlin and Brandenburg.
      The number of operations and other characteristic facts in surgical training were
      requested; 127 answers were sent back. The number of operations on colon, small
      intestine, stomach, and breast was not adequate to the required number of
      operations for specialist qualification in Berlin and Brandenburg. Although not
      representative, the inquiry shows a trend in surgical training.

PMID- 9931725
TI  - [The employment schedule act: temporal and economic limits].
AB  - This Employment Act is designed to decrease the stress burden for hospital
      doctors by removing avoidable night and shift work and is supposed to lead to an
      improved working environment. This act will also leave room for family and
      professional commitments as well as for social activities. Despite continuous
      efforts within clinical work, there is huge information deficit for detailed
      handovers and the information given to succeeding colleagues. Operations may need
      to be deferred, and misunderstandings between patients and relatives are likely
      to arise. Good co-operation with the nursing staff is suffering. A doctor is
      likely to miss around 60 days per annum through training. Legal consequences may
      arise through gaps and negligent paperwork.

PMID- 9931726
TI  - [Implementing the employment schedule act at a university clinic--"surgical
      research during illegal time periods"].
AB  - The realisation of the new regulations for working time in hospitals by law
      (ArbZG) creates a new status for clinical research. The ArbZG clearly includes
      regulations for times spent on research and teaching. The strict regulations for
      resting periods, which have to be respected, allow research activities almost
      only in time spans other than official working time. The council of the European
      Union has excluded research activities from the guidelines for working time
      regulations, so there are no limitations on the time spent on research. In
      contrast, the German regulations for working time include time spent on research,
      so there is a national disadvantage for research in comparison to other European
      countries.

PMID- 9931727
TI  - [The employment schedule act from the viewpoint of the ordinary surgeon].
AB  - In Germany, the law of labor time was instituted in hospitals on January 1st,
      1996 to regulate working hours, times of rest, breaks, and Sunday and holiday
      work. Problems in the realization of this law arise in daily practice, especially
      with regard to maximum working hours and post on-call times of rest. The
      compliance with the law would necessitate an enormous increase in new jobs for
      physicians, which is associated with an unfinanceable rise in costs. Solutions
      are either a reduction in performance or the omission to document the
      productivity. Therefore, surgeons in salaried employment in German hospitals
      constantly face the conflict of legality and legitimacy.

PMID- 9931728
TI  - [The employment schedule act--effects on the young surgeon].
AB  - Since 1. 1. 96, new regulations of working hours have been introduced in our
      hospital with regard to emergency service and compensation through leisure time.
      The average payment was reduced by 23% for surgeons on call. By this means, three
      additional surgeons could be employed. For every resident in training there is
      now less time for his residency than before. Sufficient surgical residency
      requires enough time on the ward and in the operating room. Thus, other
      conditions for residency programs are necessary to avoid unfulfilled tasks being
      pushed into the pre-existing area of non-documented working hours. Research and
      any scientific activity take place in leisure time.

PMID- 9931729
TI  - [Endoscopic cholecystectomy as cost assessment--still a learning intervention?].
AB  - Economic considerations are putting increasing pressure on surgical departments
      to avoid intra- and postoperative complications and thus additional costs. Under
      this aspect, it was investigated whether laparoscopic cholecystectomy is a
      suitable training intervention for young prospective surgeons. These physicians
      in advanced training did not have a higher intra- or postoperative complication
      rate in a preselected patient population than senior physicians or specialists.
      The additional costs per surgical intervention due to longer operation times
      required by young physicians were acceptable so that laparoscopic cholecystectomy
      as a training intervention for young colleagues can be justified.

PMID- 9931730
TI  - [Clinical anatomy in surgical education and graduate education].
AB  - On the basis of the experience that knowledge of anatomy is not as sound in
      clinical education as it should be and with a view to the new licensing
      regulations for physicians, at the Westfalische Wilhelms-Universitat Munster,
      Germany, we established an interdisciplinary anatomical education. Clinical
      practitioners from 14 different specialties together with anatomists give lessons
      in applied anatomy accompanying the dissection course, and clinical experienced
      anatomists guide senior medical students in parallel to the practical courses to
      refresh their anatomical knowledge. Conjointly clinical practitioners and
      anatomists initiate, organize and establish meetings in postgraduate surgical
      education and experimental surgery. All seminars are evaluated and have a very
      good compliance.

PMID- 9931731
TI  - [Is professional autonomy of value? From the viewpoint of the medical director].
AB  - Professional independence is one of many steps to a self-sufficient personality.
      Especially for surgeons who are used to working directly and independently during
      operations, professional independence is important. It is best achieved in a
      private surgical office. The chief position in a hospital also guarantees a
      certain independence. Professional independence is limited by many political and
      financial restrictions. Nevertheless, every surgeon should try in his own area to
      reach as much independence as possible. Even in a subordinate position, one can
      achieve a personally satisfying degree of independence by special surgical skills
      and knowledge.

PMID- 9931732
TI  - [Current status and future prospects for specializing in surgery in united
      Europe].
AB  - Specialisation within surgery is unavoidable, as it is in other disciplines.
      Motives and drawbacks are mentioned. The current situation in Europe is confused.
      However, progress in training is encouraging. The UEMS, the sections, and the
      boards are the preferred instruments for stimulation and harmonisation of
      training, C. M. E., quality control and peer review and of visitation of centres.
      The envelope concept of surgery seems to be the best answer to the structural
      problem of the distinct specialties within surgery. The duration and length of
      the common trunk in these specialties remains a difficult issue. The future of
      surgery requires the implementation of a number of assignments by the ACMT, the
      UEMS, its sections, boards and divisions.

PMID- 9931733
TI  - [Education of foreign physicians from developing countries].
AB  - Qualification as specialized consultants in Germany is nearly impossible today
      for doctors from developing countries. Due to the dense medical job market,
      foreigners from overseas countries have no chance of being hired for a normal
      hospital job, which is necessary to get the specialist education. The author,
      therefore, emphasizes the necessity to create new possibilities of financing such
      colleagues. The reputation of German medicine might depend to an important extent
      on such a possibility. It is just this period of professional formation that
      gives the most important practical professional education for the future work of
      the candidates. The author asks the German Association of Surgeons for public
      support of this problem.

PMID- 9931734
TI  - [Length of overseas research sojourn in the career path of academic surgeons].
AB  - Since there are no data concerning the results/efficiency of research stipends in
      foreign countries, the aim of this study was to analyze the experience of German
      surgeons doing research work abroad. Seventy-four fellows (residents) in surgical
      training who conducted research outside Germany between 1986 and 1995 have been
      interviewed using a detailed questionnaire. Back in Germany, the results and the
      experience gained from research abroad led in the majority of cases to a post
      doctoral degree, a high number of publications, as well as to intensified
      research efforts in the same field, using the methods learned abroad. Back home,
      the possibilities of pursuing research were often compromised by clinical
      workload. In general, better support for researchers in terms of better clinical
      and scientific perspectives is urgently needed, a demand that is voiced in
      numerous comments.

PMID- 9931735
TI  - [Graduate education for specialist in surgery in the USA--aspects for the young
      German and American physician].
AB  - Due to high standards in clinical practice and outstanding research opportunities
      in the USA, German residents wish to do a part of their surgical education in an
      American teaching hospital. Currently, German applicants must have an
      unrestricted license and a valid Standard ECFMG Certificate. For this certificate
      they must have passed Step I and II of the United States Medical Licensing
      Examination, which also includes an English test. The examination requirements
      are about to be changed. A 1-year participation in one of the 267 surgical
      residency programs is generally not possible. In Germany, American residents have
      the opportunity to apply for a supervised training year without passing the
      German medical exams. At present, there are no clinical exchange programs in
      surgery between Germany and the USA. Therefore, the German and American College
      of Surgeons should develop an exchange program for residents in surgery.

PMID- 9931736
TI  - [Is a 3-month USA sojourn of value for a German university surgeon?].
AB  - From 06/02/97 until 08/29/97, I was working at the division of Molecular Medicine
      at the North Shore University Hospital/Cornell University Medical College in New
      York on a research project concerning the role of CD14 in a chronic Gram-negative
      experimental infection model. On the one hand I had to accept three months
      absence from my family and my own hospital, as well as high travel expenses. On
      the other hand, I looked forward to important experiences abroad, contacts to
      international scientists, publication in a highly regarded journal, and last but
      not least to get to know a breathtaking city.

PMID- 9931737
TI  - [Online infection recording within the scope of total quality management].
AB  - The continuous and exact recording of infections is a condition sine qua non for
      total quality management. Therefore, at the Diakoniekrankenhaus Rotenburg (Wumme)
      a program which offers the possibility of online recording of data was integrated
      into the hospital intranet. The recording is done with network clients. The
      recording of data is supported by a series of plausibility controls. The
      advantage consists in immediate evaluation of up to date and extensive statistics
      of infections. By integration into the existing system, relevant influences and
      consequences such as the prolongation of hospitalisation, use of material, and
      frequency of reoperation can by recognized and immediately considered with high
      validity.

PMID- 9931738
TI  - [Controlling in a surgical university clinic exemplified by bilateral thyroid
      gland resection].
AB  - We calculated the overall costs of all patients who had bilateral thyroid
      resections due to benign diseases between 1995 and 1997 in a process costing
      analysis. The operating costs for an bilateral thyroid resection were 5205 DM,
      resulting in a loss of 410 DM/per case. The major cost factors were personnel
      costs (33%), operating costs on the ward (32%), and shared overhead costs (24%).
      Consequently, the main efforts for cost reduction were achieved by reducing the
      hospital stay (12.6 days in 1995 resulting in 7755 DM total costs; 6.3 days in
      1988 resulting in 4712 DM). Saving in personnel costs by reducing operating time
      is not feasible in a university department due to its obligation of training.
      Overhead costs need to be analysed in detail, because this is a hitherto
      neglected domain, where costs can be saved without damaging the quality of the
      surgical therapy.

PMID- 9931739
TI  - [Prospective study of spontaneous medical utilization of antibiotics on the
      normal surgical ward--rationale and economic aspects].
AB  - For 8 months, the spontaneous behaviour of the surgeons concerning the use of
      antibiotics (AB) was studied. The study focused on the indication itself, the
      chosen substance, the method of drug administration, and the treatment duration.
      It was evaluated whether the use of AB was rational and what the economic
      consequences of inadequate use of AB are. Of a total of 1168 pts 21.1% received
      AB, 88% of them i.v. The intention of AB treatment was therapy in 56.3%, and
      prophylaxis in 43.7% beside the regular perioperative single shot regimen. More
      than every second AB prescription was irrational. More rational behaviour
      (indication, therapy once daily, sequential therapy, no postoperative
      prophylaxis, less i.v. AB) by the prescribing surgeons would have led to a saving
      of more than 60% of the total costs of DM 215,000 without any loss of
      antiinfective efficacy. Moreover, a more rational use of AB would mean prevention
      of infectious hospitalism and would save a lot of staff time.

PMID- 9931740
TI  - [Ambulatory co-disciplinary risk-adjusted preoperative care].
AB  - Routine preoperative studies in asymptomatic patients are not helpful for
      perioperative risk evaluation, and the cost is considerable. The decision
      regarding the status of a patient for elective surgery can be accurately
      predicted in 95% of cases on the basis of a complete history and physical
      examination alone; selective testing should be preferred. Interdisciplinary
      outpatient premedication is suitable for an individual risk evaluation, and a
      significant reduction in cost and inpatient treatment.

PMID- 9931741
TI  - [Estimation for bugeting and evaluation of surgical procedures within the scope
      of comparative hospital administration. Value of LKA, PPR and DRG systems].
AB  - Comparison of costing and performances of individual departments or hospitals are
      required by the statute book of social affairs (Sozialgesetzbuch V; SGB V), but
      have not been fully introduced in Germany. LBK Hamburg, a trust of 8 hospitals
      with 17 surgical departments, evaluated the significance of performance and cost
      accounting systems such as performance and cost-accounting (LKA), nursing staff
      regulation (PPR), and the diagnosis-related group system in order to distribute a
      three-year budget (1996-1998) and to compare, e.g., performance of surgical
      departments. The DRG system seems to be the best choice, since it weights all
      cases by means in 640 groups according to the degree of difficulty. With a given
      closed budget, the DRG system may compare the actual cost with the target
      figures.

PMID- 9931742
TI  - [Use of geographic information systems (GIS) in strategic planning of surgical
      capacity within a hospital organization].
AB  - State of the art planning of clinical work means for hospitals outlining a
      catalog which is a convincing as it is profitable. Furthermore, it should easily
      remembered as a "brandname" by patients and consultants. A catalog like this is
      built up on the basis of an analysis of structures of work, costs, income, needs
      of the environment, the own work capacity and the surrounding competitors. A self
      assessment study and an analysis of the surroundings have been carried out with
      professional geographic information systems (GIS). These systems are commonly
      known in industry for the planning of sales and structuring of sales areas.

PMID- 9931744
TI  - [Multi-media CD-ROM: a new medium for improving information dissemination].
AB  - New media can be used in medicine for effective and prompt imparting of
      knowledge. We present a multimedia CD-ROM providing up to date congress
      information.

PMID- 9931743
TI  - [Computer-based training exemplified by the carotid artery].
AB  - The purpose of computer-based training (CBT) is interactive use of multimedia
      components, such as text, graphics, animation, sound, digital slide shows, and
      videos. This CD-ROM illuminates different aspects of carotid surgery:
      cerebrovascular insufficiency, sonographic and neuroradiological diagnostics,
      indications and results of carotid surgery in the literature, perioperative
      complications and new developments such as interventional procedures. Digital
      imaging (60 minutes of video sequences and 250 graphics) especially focus on
      operative standard procedures (conventional and eversion technique) and
      alternative methods. CBT is an evolving supplement to improve education programs
      in vascular surgery.

PMID- 9931745
TI  - [Development of a computer-assisted learning program for liver transplantation].
AB  - The German Society for Surgery recently decided to rename the "video library" as
      a "multimedia library", which will include also interactive, nonlinear
      computerised teachware in surgery. We report on the complex interaction of
      authors, editor, and the computer-based training laboratory, and the pitfalls
      with respect to data collection, structure, implementation, and technical aspects
      of the CD-ROM liver transplantation.

PMID- 9931746
TI  - [Development of a multimedia CD-ROM series for improving surgical education and
      continuing education].
AB  - In the past 4 years, the computer-based training laboratory of the Department of
      Surgery, University of Heidelberg, has developed a multimedia library, the
      med.LIVE-series. This CD-ROM series contains 5000 multimedia units with
      information of a uniform structure that comprises 26 CD-ROMs. These modules
      contribute significantly to the training and education of medical students and
      doctors. Furthermore, this multimedia library is intended to aid in the
      development of a database-supported online information system. Authors interested
      are encouraged to contribute to the series.

PMID- 9931747
TI  - [Analysis of the acceptance of the internet presentation of the 115th Congress of
      the German Society of Surgery].
AB  - The World Wide Web presentation of the 115th Annual Meeting of the German Society
      of Surgery was examined with regard to the frequency of hits per day and the use
      made of the online offers. The high frequency of the hits clearly shows the high
      acceptance of this medium. The temporal distribution of the hits imply that the
      group that was aimed at, namely "surgeons", have indeed been reached.

PMID- 9931748
TI  - [Information exchange via internet--possibilities, limits, future].
AB  - Today, the exchange of information in the Internet is dominated by the WWW and e
      mail. Discussion groups like mailing lists and newsgroups also permit
      communication in groups. Information retrieval becomes a crucial challenge in
      using the Internet. In the field of medicine, three more aspects are of special
      importance: privacy, legal requirements, and the necessity of transferring large
      amounts of data. For these problems, today's Internet doesn't provide a
      sufficient solution yet. Future developments will not only improve the existing
      services, but also lead to fundamental changes in the transfer technologies:
      Safer data transfer is to be ensured by new encrypting software together with the
      planned transfer protocol IPv6. Introducing the new transfer mode ATM will lead
      to better and resource saving transmission. Computer, telephone and TV networks
      will grow together, resulting in convergence of media.

PMID- 9931749
TI  - [Telesurgery--experiences from the USA].
AB  - Recent advances in telecommunications formed the basis for studies on the use of
      video and high resolution television for surgical teleconsulting. Experience from
      hospitals of the American Veterans Administration suggests the technology to be a
      valuable asset. Telesurgical techniques improve health care in remote areas, save
      costs by reducing the need for transfers, and ease the professional isolation of
      health care personnel. Clear recommendations for both primary care and referral
      centers about how to conduct telesurgical consulting are given in the text.

PMID- 9931750
TI  - [Telecommunication in routine surgical practice].
AB  - In an internal inquiry on the use of telecommunication, 267 operations were
      documented. In 62 cases an interruption was necessary: 43 of them for a second
      opinion and 29 for a new orientation resulting from findings, and in 10 cases for
      both. A purely verbal communication/consultation was sufficient in 8 cases, in 29
      questions an on-site demonstration was necessary to come to a decision. In the
      opinion of the operating surgeon, a picture transmission telecommunication system
      would have been helpful for solving the problem in 27 (44%) of the interruptions.
      Looking at the minimal invasive operations, the percentage was specially high
      (60%). We think that in future telecommunication systems can be used for time
      saving in operating rooms and on a long-term basis contribute to cost cutting and
      quality improvement in surgical routine.

PMID- 9931751
TI  - [Utility of PC-based videoconference systems in surgery].
AB  - Growing complexity of performance processes in medicine require a quicker and
      more consistent flow of information, even between distant sites of health care.
      The Regensburg model, a realisation of lean telemedicine from a low-cost domain,
      using PC-based standard videoconferencing--systems shows the use of modern
      telecommunications especially in medical spheres. In project-related evaluations,
      the efficacy of these systems as well as their use can clearly be proven. Through
      a quicker flow of information, quality improvements for all participants
      resulted, and to some extent considerable costs for health care were avoided or
      lowered.

PMID- 9931752
TI  - [Humanity and science].

PMID- 9931753
TI  - [Humanity in medicine].

PMID- 9931754
TI  - [Clinical research--an indispensible link to basic science].

PMID- 9931756
TI  - [Hospital comparison--status quo and prospects].

PMID- 9931755
TI  - [Success factors in hospital administration].

PMID- 9931757
TI  - [The public image of surgery].

PMID- 9931758
TI  - [Surgical anatomy of the esophagus and stomach in relation to stomach pull
      through].
AB  - Surgical-anatomical related risks with respect to: 1. Resection of the esophagus:
      As long as the tumor is confined to the wall, there is no risk of bleeding
      because, close to the esophagus, all the vessels have become minute; when torn,
      hemostasis will occur. For the same reason the recurrent nerves are not
      endangered as long as the main trunk is not disrupted and the anastomosis not
      performed within the cranial 3-5 cm. 2. Substitute: Preservation of the
      gastroduodenal and superior mesenteric arteries is essential to supply the
      gastric tube via the gastroepiploic vessels. The fundus, i.e., the top of the
      tube in particular in gastroplasty procedures is extremely vulnerable to pressure
      and tension.

PMID- 9931760
TI  - [Treatment of soft tissue damage--definitive management].
AB  - Fractures of the extremities combined with soft tissue damage are still a big
      challenge for the orthopaedic surgeon. Medical mismanagement leads very often to
      osteomyelitis and high treatment costs. Radical debridement is the key to therapy
      success. Closure of soft tissue lesions has to be done within 1 week. Methods of
      choice are vacuum sealing, meshgraft, flap transfer and the Ilisarov procedure.
      The chosen tool has to be harmonized with the fracture classification. Only
      individual decisions are possible. For the best results, orthopaedic surgeons
      should have a good knowledge of the reconstructive possibilities.

PMID- 9931759
TI  - [Surgical anatomy in lung resections].
AB  - When thoracic/lung surgery is performed autodidactically, intraoperative
      catastrophes and complications are to be expected. Atypical partial resections
      must be distinguished from typical resections of anatomical parechyma units
      (standard operations). More extensive operations which involve additional lung
      structures (lung lobes, trachea, bronchi) or attached organs (chest wall, heart,
      diaphragm etc.) are technically demanding. The larger the anatomical unit, the
      closer to the heart all vessels have to be arranged and, not seldom this means
      intrapericardially with clamping of the left atrium. All structures of the hilus
      are suitable for closing with staplers or suture. In the case of pneumonectomies,
      central lung structures can be cut most easily by cutting ligaments (Lig.
      anterior superius, Lig. pulmonale inferius). Pictures and photographs demonstrate
      specialties of topography of bilateral central lung structures in the context of
      extended resections.

PMID- 9931761
TI  - [Surgical anatomy with special reference to reconstruction in severe hand
      injuries].
AB  - The treatment of mutilating hand injuries demands exact knowledge of the anatomy
      of the hand. Minor faults in the operative treatment may lead to severe permanent
      functional impairment of the hand. Today, primary reconstruction of all injured
      structures is performed. The aim is reconstruction of function as well as
      cosmesis of the hand. The principle components of reconstruction are: position,
      prehension, sensibility, trophic, and cover of the hand.

PMID- 9931762
TI  - [Reconstruction of the female breast with free transverse lower abdominal flap as
      perforator flap].
AB  - The DIEP flap was introduced to autogenous breast reconstruction to avoid defects
      in the abdominal rectus muscle as created in pedicled and free TRAM flaps. This
      flap has the same soft tissue dimension as the other transverse abdominal flaps.
      In addition it has the advantages of free TRAM flaps, i.e. good perfusion and
      excellent aesthetic qualities and offers the possibility to reduce donor site
      morbidity.

PMID- 9931763
TI  - [Quality of life of patients with fecal incontinence].
AB  - Using the Gastrointestinal Quality of Life Index (GIQLI) we investigated the
      quality of life in a consecutive series of 35 patients with faceal incontinence
      compared with patients suffering from haemorrhoidal disease (n = 96), fissure in
      ano (n = 38) and healthy controls (n = 75). The mean score for the different
      groups were as follows: incontinence 93 (65% of best possible score of 144),
      haemorrhoids 120 (83%), fissure 104 (72%) and controls 134 (93%). Incontinent
      patients had the significantly lowest overall GIQLI.

PMID- 9931764
TI  - [Passive electrostimulation therapy of the anal sphincter is inferior to active
      biofeedback training].
AB  - Anal incontinence can be treated by conservative therapy if a significant
      anatomical sphincter defect has been excluded. We compared electrostimulation
      therapy with biofeedback training in a prospective study. Results showed that up
      to two thirds of all patients can be treated successfully, whereby the results of
      biofeedback were better than those of electrostimulation.

PMID- 9931766
TI  - [Avoiding abdominal roentgen images in acute abdominal pain--evaluation of a
      simple clinical decision support aid].
AB  - The evaluation of a simple decision aid in the diagnosis of acute abdominal pain
      shows that plain abdominal x-rays to exclude bowel obstruction can be avoided if
      less than two of the following symptoms are present: distended abdomen, increased
      bowel sounds, history of constipation, previous abdominal surgery, age over 50 or
      vomiting.

PMID- 9931765
TI  - [Megacolon in adults--the spectrum of underlying intestinal innervation
      disorders].
AB  - The association of megacolon in adults and Hirschsprung's disease was reevaluated
      by the morphological assessment of the enteric nervous system. Whole-mount
      preparations of the resected colonic segments and an immunohistochemical
      treatment with the pan-neuronal marker protein gene product 9.5 allowed an
      optimal visualization of the entire intramural nervous plexus layers. The
      findings included different forms of intestinal neuronal malformations
      (hypoganglionosis, neuronal intestinal dysplasia, and heterotopic ganglia) apart
      from classic aganglionosis, thus indicating their etiologic relevance to the
      development of megacolon in adults.

PMID- 9931767
TI  - [Surgical laparoscopy in acute abdomen].
AB  - In 582 patients, laparoscopy was performed for acute abdominal pain and symptoms
      of acute abdomen. It allowed a clear diagnosis in 96% as compared to 42% by
      sonography and 25% by X-ray. In 134 cases (22%) laparotomy (i.e. unnecessary
      appendectomy) could be avoided. In 42% surgery could be performed
      laparoscopically, and 36% required surgery by laparotomy.

PMID- 9931768
TI  - [The abdominal emergency after heart surgery interventions].
AB  - In 4726 patients undergoing cardiopulmonary bypass surgery in a 5-year period 15
      major acute abdominal complications (0.3%) occurred, with an overall mortality
      rate of 47%--compared with a mortality rate of 3.2% for all patients undergoing
      heart surgery (p < 0.0001). Patients with combined cardiac operation (ACB and
      valve replacement) or those requiring an intraaortic balloon pump were more
      likely to develop abdominal complications; however, complications can not be
      predicted. The focus should be on early diagnosis and therapy, especially in
      acute mesenteric ischemia, in close cooperation between heart and general
      surgeons to improve prognosis.

PMID- 9931769
TI  - [Risk factors for postoperative course after resection for Crohn disease].
AB  - Conservative surgery in Crohn's disease causes multiple enteral anastomoses. In
      120 patients who underwent resectional surgery for Crohn's disease with a total
      of 165 anastomoses we analyzed the risk factors (a) number of anastomoses per
      operation, (b) preoperative cortisone, and (c) the resection margins in relation
      to the major postoperative complications. With a total of five major
      complications and no mortality we could not observe an increased risk for a
      higher morbidity in Crohn's disease surgery with multiple anastomoses.

PMID- 9931770
TI  - [Transforming growth factor-beta controls pathogenesis of Crohn disease].
AB  - The pathogenetic mechanisms which contribute to the progression of Crohn's
      disease are still not known. Transforming growth factor-beta (TGF-beta) and its
      subtypes are multifunctional polypeptides which regulate immunological processes
      as well as the synthesis of the extracellular matrix and fibrogenesis. In the
      present study, Crohn's disease tissue samples of 18 patients undergoing
      intestinal resection were analyzed by Northern blot analysis, in situ
      hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type
      I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression
      of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue
      samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%,
      72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and
      immunostaining revealed that there was frequent coexpression of TGF-beta with its
      signaling receptors. Our data indicate that TGF-beta and their receptors seem to
      be involved in the pathogenesis of Crohn's disease. Their enhanced expression
      might contribute to the increase in extracellular matrix resulting in fibrosis
      and subsequently in intestinal obstruction.

PMID- 9931771
TI  - [Therapy planning and surgical indications for Crohn-associated anal fistulas].
AB  - A prospective study conducted from April 1988 to April 1998 in 83 patients with
      anal fistulas associated Crohn's diseases registers and evaluates data regarding
      the type of fistula, the planned therapy, the operative procedure, and the
      therapy itself. The choice of the operation time with special regard to the type
      of fistula and the presence of proctitis as well as the interdisciplinary
      management in cooperation with the gastroenterologist and the strict observance
      of the operative procedure for the different types of fistulas enable
      individually defined surgical treatment of anal fistulas associated with Crohn's
      disease. It is important that the primary intervention be performed by a surgeon
      who is experienced in classifying the different types of fistulas because of the
      recurrence rate of 23% and the required interval between the first and final
      surgical intervention and so that patients are well informed.

PMID- 9931772
TI  - [Rectovaginal fistulas in patients with Crohn disease--therapy and prognosis].
AB  - Perianal and especially rectovaginal fistulas in Crohn's disease represent a
      great therapeutic dilemma. Surgical intervention is mandatory in the impending
      destruction of the anal sphincter mechanism, weighed against the efficacy of the
      methods available. We report on the surgical approach in 25 women with
      rectovaginal fistula, concluding that either levator plasty or mucosal flap is
      the procedure of choice.

PMID- 9931773
TI  - [Surgery for obesity: a current trend or a specialty to be taken seriously?].
AB  - We performed gastric restriction operations in our hospital on 320 patients. 55%
      of them lost 50% of their excess weight within 7 months. The success of this kind
      of operation depends on a comprehensive therapeutic concept in addition to the
      surgical treatment.

PMID- 9931774
TI  - [Patient selection for laparoscopic gastric banding operation].
AB  - This study presents methods and results of a systematic selection of patients for
      laparoscopic gastric banding. A seven-step selection process considering
      anamnestic data, comprehensive counseling of patients and relatives, standardized
      psychological evaluation, specific medical work-up, including functional foregut
      testing, and economic issues was performed to select 50 of 163 referred patients
      (30.1%) for surgery. Long-term follow-up is needed to assess the value of this
      selection process.

PMID- 9931775
TI  - [Laparoscopic gastric banding for treatment of morbid obesity].
AB  - The laparoscopic implantation of the LAP-BAND is a minimal invasive technique in
      obese patients. The effectiveness is comparable to that of gastroplasty. In all
      186 patients were treated laparoscopically. The conversion rate was 0%. There
      were no death. In 0.5% there were intraoperative complications; 3% complications
      were caused by the port system; and 4% of the late postoperative complications
      were related to the LAP-BAND (pouch dilatation, slippage).

PMID- 9931776
TI  - [Laparoscopic gastric banding operation: technique, results and complications in
      370 cases].

PMID- 9931777
TI  - [Reducing concomitant illnesses of morbid obesity after gastric banding].
AB  - Kuzmak's adjustable gastric banding procedure is well established and has proven
      to be efficacious in obese patients. After gastric banding we observed a good
      weight loss and an improvement in metabolic syndrome diseases. Therefore we were
      able to reduce the dosage of preoperative medication in patients with diabetes or
      hypertension.

PMID- 9931778
TI  - [Quality of life after inguinal hernia operation--results of a prospective study
      (Shouldice, Lichtenstein, TAPP)].
AB  - Data concerning quality of life and rehabilitation after inguinal hernia repair
      are still poor. A prospective survey on 269 patients was conducted following
      standardized Shouldice, Lichtenstein and TAPP hernioplasty by means of
      questionnaire. General health perception, pain scores and physical activity were
      significantly improved by all of the mentioned techniques. Laparoscopic repair
      was beneficial in indirect, recurrent and bilateral hernia and small defects of
      the transverse fascia.

PMID- 9931779
TI  - [Surgery of inguinal hernia with local anesthesia--technique and results of a
      minimal invasive procedure].
AB  - In three prospective, randomized studies we analyzed the advantages of local
      anesthesia in patients with primary inguinal hernias. Each study consisted of 100
      cooperative adults, using an open approach and the transinguinal procedure. Due
      to reduced postoperative complications, increased effectiveness of hospital
      resources, earlier discharges and a high acceptance by the patients, local
      anesthesia is the ideal treatment in adult hernia repair.

PMID- 9931780
TI  - [Reconstruction of incisional hernias with defined tensiometrically controlled
      tension--a possibility for anatomically correct reconstruction of the abdominal
      wall].
AB  - The repair of incisional hernias of the abdominal wall is characterized by high
      rates of recurrence if arbitrary tension is applied. A rationale for selecting
      the appropriate reconstruction technique as defined by intraoperative tension
      measurements has proven effective and successful. Here, the inlay/onlay technique
      tolerates up to 3.5 kilopounds (kp). Our results show that using this technique,
      complete reconstruction is possible in 65% of cases with a recurrence rate of
      2.3%.

PMID- 9931781
TI  - [Laparoscopic hernia repair of recurrent hernias].
AB  - Successful treatment of recurrent inguinal hernias is still a problem, in spite
      of the availability of several different methods. We present our experience with
      laparoscopic TAP repair, which was performed in 154 patients with 168 recurrent
      inguinal hernias after traditional anterior repairs. Our results show an
      acceptable complication rate (5.4%, n = 9) and a low re-recurrence-rate (1.8%, n
      = 3), combined with the benefit of the minimal access technique, so that this
      procedure can be recommended in recurrent inguinal hernia repair.

PMID- 9931782
TI  - [Intraoperative isotope-controlled probe localization after somatostatin receptor
      scintigraphy of occult neuroendocrine tumors].
AB  - Intraoperative gamma detection of GEP tumors with a manual probe following i.v.
      111In-DTPA-D-Phe1-Pentetreotide is a new and expensive procedure. This study
      analyses its value in nine patients with occult lesions (undetected
      preoperatively). All lesions with the exception of a 8-mm liver metastasis were
      correctly diagnosed intraoperatively. The tumor/normal tissue ratios were in vivo
      1.3 (1.1-2.0) and ex vivo 23.0 (9.4-24.0). False-positive results were obtained
      three times in vivo and once ex vivo. Sensitivity was 89% and specificity 57%,
      respectively. All lesions were successfully detected by careful surgical
      exploration. We conclude that intraoperative gamma detection offers little
      additional information over standard diagnostic procedures.

PMID- 9931783
TI  - [Subtotal retroperitoneoscopic adrenal gland resection--an alternative to
      adrenalectomy?].
AB  - Primary adrenal tumors were removed in 24 patients by the posterior
      retroperitoneoscopic approach, maintaining tumor-free parts of the ipsilateral
      adrenal gland. These partial adrenal resections did not cause a significantly
      different operating time or blood loss compared to 58 complete adrenalectomies
      performed during the same period. All 20 patients with hormonally active tumors
      are biochemically and clinically cured (mean follow-up 18 months). In selected
      cases the retroperitoneoscopic subtotal adrenal gland resection is a safe
      procedure, which can potentially maintain the function of the adrenal gland's
      cortex.

PMID- 9931785
TI  - [Benign thyroid gland diseases in childhood and adolescence--early indications
      for surgical therapy].
AB  - Thyroid diseases in childhood and adolescence are mainly diffuse goiters due to
      iodine deficiency, which should be treated conservatively. Thyrotoxicosis, in the
      majority due to Graves' disease, is usually treated conservatively, and
      remissions can be expected in only 20%. Our prospective data from 21 patients
      under 20 years of age show that primary surgery is favored in young patients
      because of its prompt and permanent success. Minimal postoperative morbidity is
      the precondition for this approach. Preoperative conservative treatment for more
      than 2 years causes a significantly higher incidence of persistent ophthalmopathy
      postoperatively. Thyroid nodes in children are malignant in 20-30%. Consequently,
      all children and adolescents with nodular thyroid disease should have a primary
      lobectomy.

PMID- 9931784
TI  - [Effect of primary surgical therapy on the course of C-cell carcinoma of the
      thyroid gland].
AB  - The effect of the type of initial surgery for medullary thyroid carcinoma on the
      outcome is obscure. Some 40 patients with hereditary medullary thyroid carcinoma
      underwent either thyroidectomy and modified radical neck dissection (n = 18),
      subtotal thyroid resection (n = 10), or thyroidectomy (n = 12), partly with
      selective lymphadenectomy, as initial surgery. Patients who underwent
      thyroidectomy and modified radical neck dissection as their first operation had
      higher cure rates and lower morbidity. Thus the initial procedure is decisive for
      the further outcome in patients with hereditary medullary thyroid carcinoma.

PMID- 9931787
TI  - [Selective (= morphology and function dependent) surgery of nodular struma:
      relationship to risk of recurrent laryngeal nerve paralysis by dissection and
      manipulation of the nerve].
AB  - In a consecutive series of 1,143 first operations for benign nodular goiter with
      1,928 "nerves at risk", the incidence of postoperative recurrent laryngeal nerve
      palsy (RLNP) was analyzed related to the extent of the operative procedure (node
      excision up to lobectomy) and manipulation of the nerve (identification,
      mobilization, non-identification). The incidence of early RLNP increased with the
      extent of the operation (1.2% up to 4.8% in lobectomy) and with the extent of
      nerve manipulation (up to 3.1% in extensive mobilization). However, the rate of
      permanent RLNP was higher after non-identification of the nerve (0.6% vs 0%),
      especially in the group of conventional subtotal resection (1.3% vs 0%; p <
      0.05). As a rule, the nerve should be identified, especially in conventional
      subtotal resection, when possible without further mobilizing manipulations.

PMID- 9931786
TI  - [Surgical procedure for hyperthyroidism in children and adolescents].
AB  - The high recurrence rate of hyperthyroidism after drug therapy in Graves disease
      and the high incidence of differentiated thyroid cancer in autonomously
      functioning thyroid nodules are the most common indications for surgical
      treatment in children and adolescents (less than 18 years old). Between April
      1986 and March 1998, 101 adolescents were operated on: 24 children (23.8%) for
      Graves disease, 9 adolescents (8.9%) for autonomously functioning thyroid
      nodules. Surgery for hyperthyroidism is recommended in children and adolescents
      because of the low morbidity, the guarantee that this approach will successfully
      treat hyperthyroidism and the necessity for histological exploration.

PMID- 9931789
TI  - [Intraoperative neuromonitoring of the recurrent laryngeal nerve--routine use in
      thyroid gland surgery].
AB  - We present a simple and reliable method for identification of the recurrent nerve
      by intraoperative stimulation. An electromyographic record from the vocal muscle
      is obtained using a bipolar needle electrode inserted through the cricothyroid
      membrane. The recurrent nerve could be easily identified in 176 cases out of 181
      nerves at risk (97.2%). We have not seen any cases of recurrent nerve paralysis
      and discuss the advantages of intraoperative neuromonitoring as a routine
      procedure.

PMID- 9931788
TI  - [Continuous monitoring of the recurrent laryngeal nerve].
AB  - A new "all in one" sensing device for tracing and continuous intraoperative
      monitoring of the recurrent laryngeal nerve during thyroid surgery is described.
      The system, based on a double ballooned endotracheal tube, is atraumatic, easy to
      use and sensitive even to imminent trauma to the nerves. The most striking
      feature of this instrument is that it operates outside the sterile operating
      field and truly monitors continuously throughout the operation.

PMID- 9931790
TI  - [Results of two-stage thyroidectomy in differentiated thyroid gland carcinoma].
AB  - This retrospective study (1986-1996) investigated 60 patients after total
      thyroidectomy indicated by a differentiated thyroid carcinoma. Analyzing the rate
      of paralysis of the recurrent nerve after secondary thyroidectomy due to the
      timing of the second operation, we found that only patients with secondary
      thyroidectomy having their second operation at an interval > 7 days suffered from
      permanent paralysis of the recurrent nerve. In conclusion, a second radical
      surgical procedure must be performed as early as possible to minimize
      complications.

PMID- 9931791
TI  - [Surgery of nodular goiter: postoperative hypocalcemia in relation to extent of
      resection and manipulation of the parathyroid glands].
AB  - In a series of 579 consecutive first operations for bilateral benign nodular
      goiter, the incidence of hypocalcemia was analyzed related to the extent of the
      bilateral operative procedure and manipulation of the parathyroid glands
      (identification, mobilization, non-identification). The incidence of early
      hypocalcemia increased with the extent of the operation and with increasing
      manipulation of the parathyroid glands. However, permanent hypocalcemia was
      exclusively found after identification of less than three parathyroid glands
      (1.5% vs 0%), most evidently after bilateral conventional subtotal resection
      (3.5%). As a rule, the parathyroid glands should be identified routinely,
      especially in conventional subtotal resections, if possible without further
      mobilizing manipulations.

PMID- 9931792
TI  - [Induction of early endotoxin tolerance with atoxic endotoxin--a new method for
      preventing sepsis syndrome].
AB  - The induction of early-phase endotoxin tolerance in a procine endotoxin shock
      model by atoxic LPS from Rhodobacter sphaeroides led to a significant extension
      of the survival time (p < 0.0179). The protective effect of the non-specific
      tolerant state also led to an enhancement of cardiorespiratory parameters during
      the continuous endotoxin challenge. Non-specific stimulation of host defense
      mechanisms with atoxic endotoxin as prophylactic agent in surgical patients at
      risk may prove to be beneficial in the future.

PMID- 9931793
TI  - [Cause-oriented prevention of nosocomial pneumonia: the HI-LO EVAC tube].
AB  - Surgical high-risk patients were studied in a prospective randomized trial
      regarding nosocomial pneumonia (NP) using a subglottic lavage (SL). A total of
      100 patients were investigated, in whom the primary infection was localized in
      the oropharynx. Independent of the kind of stress ulcer prophylaxis, intermittent
      subglottic lavage reduces the incidence of NP drastically to 3%, which is
      however, without statistical significance.

PMID- 9931794
TI  - [Early extubation vs. late extubation after esophagus resection: a randomized,
      prospective study].
AB  - In the present study, so far 131 patients with transmediastinal esophagectomy and
      104 patients with transthoracic esophagectomy were investigated concerning
      clinical results (complication rate/mortality) following early extubation (within
      6 h postoperatively) or prolonged ventilation (> 24 h). Age tumor stage and risk
      profile did not differ between the two patient groups. RESULTS: Following
      transmediastinal esophagectomy, early extubation is superior concerning "stay in
      the ICU" (7.1 days vs 12.3 days) and complication rate (13.4% vs 32.8%). In
      contrast, following transthoracic esophagectomy, hospital lethality increases
      after early extubation (9.8% vs 1.9%).

PMID- 9931796
TI  - [Plasma separation combined with CVVHF in septic and SIRS patients].
AB  - In a prospective non-randomized trial, 59 patients with sepsis (n = 43) and SIRS
      (n = 16) were treated on a surgical intensive care unit. In 22 patients
      plasmapheresis in combination with continuous venovenous hemofiltration (CVVHF)
      was administered. Lethality was 56% in the sepsis group; in the therapy group
      lethality was significantly lower in patients with plasmapheresis, even though in
      this population the organic failure rate was higher. Finally the dependency of
      lethality and age was similar in both groups. Lethality at 22% in the
      plasmapheresis group with double organ failure was significantly lower (P > 0.01)
      than in controls. Reduction of lethality seemed to be as high as 18% in patients
      with sepsis, while patients with SIRS did not profit from the additional therapy.
      A prospective randomized trial in sepsis and double organic failure should be
      projected.

PMID- 9931797
TI  - [Is modification of systemic inflammatory response syndrome and multiple organ
      failure by parenteral feeding possible?].
AB  - In this prospective, randomized, double-blind controlled clinical study, 29
      patients after severe trauma (ISS about 40) were randomized to receive either
      IMPACT (Test) or an isonitrogenous isocaloric diet (Control). The primary study
      endopoints were the incidence of SIRS and MOF (definitions according to Bone,
      Goris and Sauaia). Test-fed patients developed significantly less SIRS between
      days 1 and 28 (8 vs 13.3, P < 0.05) and especially between days 8 and 14 (3 vs
      6.2, P < 0.001). In the control group the Goris score was significantly worse (P
      < 0.05) on days 3, 4, 6, 7, 10, 11, 16, 17 and the Sauaia score on days 8, 9, 10,
      11 (P < 0.05, P < 0.01). According to the results, an arginine, omega-3-fatty
      acids and nucleotide-enriched diet during early enteral feeding leads to
      reduction of SIRS and MOF scores after severe multiple injury.

PMID- 9931795
TI  - [Immune stimulation with G-CSF (Neupogen) in septic patients with immune
      paralysis].
AB  - Ten patients with sepsis (HLA-DR+ monocytes < 30%) were treated with G-CSF (300
      mg Filgrastin, Neupogen 30, Amgen). All patients showed a rise in HLA-DR+
      monocytes during therapy. In six patients the high level of HLA-DR+ monocytes
      persisted after therapy; these patients survived. In the other four patients the
      number of HLA-DR+ monocytes declined after application of G-CSF, and the patients
      died of multiorgan failure. Some patients with sepsis might profit from
      immunestimulating therapy with G-CSF, but further studies are needed to prove
      whether or not this is true.

PMID- 9931799
TI  - [Intervention-adjusted intraoperative volume substitution--an example of surgical
      anesthesiological cooperation].
AB  - Since 1996 a simple classification of surgical interventions has been used to
      guarantee adequate intraoperative anesthesiological volume management. Use of
      this classification, including extension of operation and operative trauma,
      resulted in 45% less substitution with blood components in comparison to that
      observed in 1995.

PMID- 9931798
TI  - [Predictive role of IL-6 for multi-organ dysfunction syndrome MODS) in severely
      injured patients in the early intensive care phase].
AB  - Interleukin-6 seems to have a predictive value for the multiple organ dysfunction
      syndrome (MODS) in the early period after trauma.

PMID- 9931800
TI  - [Effect of kinetic therapy on the course of treatment of patients with post
      traumatic lung failure].
AB  - This study was conducted to investigate the effects of intermittent prone
      positioning of patients with post-traumatic respiratory failure (paO2/FiO2 < 280
      mm Hg) in comparison with conventional therapy in a supine position. Although the
      severity of injury of the prone-positioned patients was much higher (ISS 35.8 vs
      24.5), the ventilation time (32 vs 31 days) and ICU stay (39 vs 36 days) were
      similar to patients treated in the supine position. Besides the beneficial effect
      of prone positioning on oxygenation, for the first time we have evidence that
      prone positioning improves the outcome of patients with post-traumatic
      respiratory failure.

PMID- 9931801
TI  - [Early postoperative nutrition after elective colonic surgery].
AB  - Our intent was to show that immediate postoperative oral feeding of a regular
      diet after elective open colorectal surgery is safe, feasible and can be
      tolerated by the patients. Our prospective study included 96 consecutive
      patients, and their results were compared with those of the literature.
      CONCLUSION: Early oral feeding after elective colorectal surgery is safe
      (morbidity: 12.5%; mortality: 2%); it can be tolerated without symptoms by a
      majority of patients (85%); it is easy, feasible, and shortens the postoperative
      length of hospital stay (10.6 days).

PMID- 9931802
TI  - [Enteral feeding of problem patients: replacement of surgical catheter
      jejunostomy by an endoscopic concept].
AB  - Percutaneous endoscopic gastrostomy (PEG), is widely used as a safe, effective
      method of providing enteral nutrition to patients in whom oral feeding is not
      possible. However, in patients with malnutrition after partial or total
      gastrectomy, anastomotic insufficiency after gastric resection or esophageal
      resection with gastric pull-up, esophageal perforation and fistulas, the stomach
      cannot be punctured. In these cases endoscopic percutaneous jejunostomy (EPJ) by
      direct punction of the small intestine is a reasonable alternative; the technique
      is described, and the results of a series of 103 EPJs are reported.

PMID- 9931803
TI  - [Reversal of therapy of postoperative complications by measuring lung water].
AB  - Our data suggest that the indicator dilution technique allows differentiated and
      early prediction of cardiopulmonary complications during the postoperative
      period. This leads to significant changes in fluid therapy to prevent organ
      failure.

PMID- 9931804
TI  - [Endoscopic therapy of gastrojejunal dissociation in intensive care medicine].
AB  - The object of this study was to evaluate the advantages of a new three-lumen tube
      (Trelumina) and a percutanous endoscopic gastrostomy (EntriStar) with a jejunal
      insertion tube (EntriStar) as a safe way to administer early enteral nutrition
      and simultaneous gastric decompression and fast reduction of high gastric reflux
      in critical care patients. Normalization of high gastric reflux and the patient
      nutrition goal were reached by Trelumina and the EntriStar within 4 days, and
      enteral feeding by those two systems depressed the nutrition costs by more than
      90% compared to total parenteral nutrition. In conclusion, the placement of the
      Trelumina and the EntriStar is a safe, successful, and inexpensive means of
      providing early enteral nutrition and simultaneous gastric reflux reduction in
      critical care patients.

PMID- 9931805
TI  - [Thrombophlebitis profunda in patients after conventional and laparoscopic
      cholecystectomy].
AB  - The purpose of this study was to compare the incidence of deep venous thrombosis
      (DVT) in patients undergoing uncomplicated laparoscopic cholecystectomy and in
      whom conversion to laparotomy was required. Using the Duplex Doppler examination,
      we found higher incidence of DVT in patients who required conversion than in
      those who did not (47 vs 58%). Prolonged prophylaxis with low-molecular weight
      heparin should be considered in these patients.

PMID- 9931806
TI  - [Perioperative therapy of HIV infections].
AB  - A meta-analysis of the literature demonstrates high operation complication rates
      in HIV-positive patients. Own experience connected with a general hospital in San
      Francisco, University of California, indicates that such an analysis provides the
      surgeon with the possibility of optimizing the treatment of HIV-positive patients
      in the perioperative phase.

PMID- 9931807
TI  - [Radiation dosage of the surgery from intraoperative roentgen procedures: risks
      and dose management in the operating room].
AB  - A prospective study of 24 operative procedures with fluoroscopic guidance was
      undertaken to measure the radiation exposure of the primary surgeon. The dose
      received per procedure ranged from 0.6 to 259.3 microSv and was well within the
      government guidelines. An in vitro study during lateral fluoroscopy proved the
      position of the surgeon close to the image converter was irradiated with less
      scatter.

PMID- 9931808
TI  - [Is ultrasound examination in acute appendicitis dispensable? Acute Abdominal
      Pain Study Group].
AB  - In a prospective multicenter observational trial, the performance and clinical
      benefit of ultrasound of the appendix was evaluated in the clinical routine.
      Ultrasound of the appendix was performed in 870 of 2280 patients (38%); the
      overall sensitivity was 55% (range: 13 to 90%), specificity 95%, positive and
      negative predictive value 81 and 85%. There was no correlation between the
      frequency or accuracy of ultrasound and the accuracy of the clinician, the
      negative appendectomy or perforation rate.

PMID- 9931809
TI  - [Effect of ultrasonic diagnosis and incidence of appendectomy and laparoscopy].
AB  - A total of 330 of 409 patients with suspected acute appendicitis were examined by
      ultrasound, and an appendectomy was performed in 146 patients. The negative
      appendectomy rate was 7% with preoperative ultrasound (n = 72) compared with 31%
      without (n = 74). Laparoscopy did not reduce the negative appendectomy rate, but
      was useful in patients with opposing clinical and sonographical findings.

PMID- 9931810
TI  - [The diagnostic value of rectal examination of patients with acute appendicitis].
AB  - The results of rectal digital examinations performed on 477 patients upon
      admission with histopathologically proven acute appendicitis from a total of 2280
      patients with acute abdominal pain were analyzed. Although 13.7% of the patients
      experienced pain on the right side and 7.4% pain in the pouch of Douglas during
      rectal examination, none of the rectal examination parameters was statistically
      significant for the diagnosis of acute appendicitis. There are well established
      and statistically significant clinical indications, such as guarding, rigidity,
      rebound tenderness or abdominal distention that actually make the unpleasant
      rectal-digital examination superfluous for patients with suspected appendicitis.

PMID- 9931811
TI  - [Pancreatic tumor of uncertain origin--a therapeutic dilemma?].

PMID- 9931812
TI  - [Diagnosis and therapy of pancreatic pseudocysts in chronic pancreatitis].
AB  - Cystojejunostomy is the operation of choice in patients with pancreatic
      pseudocysts with pain and/or local complications if no resection procedure is
      necessary. This procedure can be performed safely after 6 weeks with a low
      morbidity and mortality and good long-term results compared to conservative
      treatment.

PMID- 9931813
TI  - [Biliary pancreatitis--epidemiology, progress with a new therapy concept?].
AB  - In our patients with symptomatic cholelithiasis (n = 3618 in a 6-year period), we
      found biliary pancreatitis in 4.4% (0.4% severe pancreatitis). Because of
      therapeutic splitting (ERC/EPT, followed by laparoscopic cholecystectomy), we are
      able to reduce the hospital stay by about 60%, reduce morbidity significantly (P
      < 0.05) and reduce lethality.

PMID- 9931814
TI  - [Surgical ultrasound--indications for "therapeutic splitting" in complicated
      gallstones].
AB  - The use of selective therapeutic ERCP, indicated by ultrasonographically detected
      dilation of the common bile duct, is a safe procedure with low morbidity, no
      mortality and a significant reduction in the need for conversion to open
      cholecystectomy.

PMID- 9931816
TI  - [Differential achalasia therapy].
AB  - The early relief of esophageal outflow obstruction in patient with achalasia
      diminishes complaints and avoids deterioration as a result of this disease. The
      pneumatic myotomy of the lower esophageal sphincter is the initial therapeutic
      concept. After two unsuccessful dilations, the laparoscopic myotomy with
      semifundoplication shows the best long-term results in the treatment of achalasia
      with fewer complications.

PMID- 9931815
TI  - [Transoral video-endoscopic esophago-diverticulotomy of Zenker's diverticulum
      with the Endo-GIA device].
AB  - The transoral endoscopic staple-assisted esophagodiverticulotomy is a new
      technique for the treatment of Zenker's diverticulum. In the period of July and
      August 1997, four older high-risk patients underwent this new technique with good
      results. To assess the value of this technique long-term follow-up studies as
      well as comparative trials will be needed.

PMID- 9931817
TI  - [Combined pH measurement and multiple impedance variation assessments--validation
      of a new technique for detection of non-acid reflux in the esophagus].
AB  - In 10 patients with gastroesophageal reflux disease, defective lower esophageal
      sphincter and normal motility pH and impedance were measured parallel over 24
      hours. All patients had a reflux score > 40 with a total of 736 reflux episodes
      registered by the pH metry of which 724 (sensitivity: 98.9%) were recognized by
      impedancemetry and with additional 292 reflux phases registered at a stomach pH >
      4 by the impedancemetry of which none was recognized by the pH metry as a reflux
      of pH > 7. With the multiple impedancemetry a reliable recognition of
      gastroesophageal reflux is possible, independently of the pH and this makes it
      possible to recognize gastroesophageal reflux also at a non acid milieu of the
      stomach, e.g. under acid suppression medication or after stomach resection.

PMID- 9931818
TI  - [Diagnosis of suture dehiscence in the gastrointestinal tract. "Sufficiency" of
      radiology and endoscopy].
AB  - Since radiological methods are standard for the diagnosis of anastomotic
      insufficiencies in the gastrointestinal tract, endoscopy, with direct access to
      the crucial site for visual verification and direct application of contrast
      media, offers remarkable advantages in diagnostic efficiency. Additional,
      immediate therapeutic management of these threatening conditions, especially in
      critical and problematic cases, is possible by interventional endoscopy.

PMID- 9931819
TI  - [Fas/Fas ligand mRNA are expressed in Helicobacter pylori infected mucosa].
AB  - Helicobacter pylori (Hp) seems to possess an inflammatory as well as immun
      modulatory potential. The investigation revealed that both Fas and FasLigand are
      expressed in the gastric mucosa independently of the Hp infection status and with
      no significant difference to the expression profile in PBMC. In conclusion, Fas
      FasLigand interaction could play a role in immune regulation of Hp gastritis and
      induction or mediation of epithelial injury.

PMID- 9931820
TI  - [Differentiation of sphincter insufficiency and constipation after surgical anal
      atresia treatment: value of a new continence score].
AB  - Surgery of anorectal malformations was evaluated by continence scores, excluding
      constipation. The authors introduce a new score considering the case history and
      clinical parameters that differentiate sphincter insufficiency and overflow
      incontinence due to constipation.

PMID- 9931822
TI  - [Elastic intramedullary nailing--a concept for treatment of unstable forearm
      fracture in childhood].
AB  - The standard treatment in forearm fractures of children is usually conservative.
      Unstable fractures of the proximal parts of the forearm often show poor results
      after nonoperative management, requiring surgical intervention. We report on 30
      children from 4 to 14 years of age who were treated by elastic intramedullary
      nailing. Sixteen patients were treated by intramedullary pinning immediately
      after the accident; 14 required intramedullary nailing after failure of the
      conservative treatment and fracture redislocations. At the time of follow-up 6
      months later, functional results were "excellent" in 24 children, "good" in 5 and
      "fair" in one child. There were no serious complications apart from the
      occurrence of one delayed union. According to these results intramedullary
      nailing can be recommended for the treatment of unstable fractures of the
      proximal and middle parts of the forearm in children.

PMID- 9931821
TI  - [Improved continence after Pena operations in anorectal abnormalities].
AB  - Studies investigating the functional outcome after operative treatment of high
      and intermediate forms of anal and rectum atresia have shown better results for
      the Pena procedure than for other forms of pull-through procedures. Follow-up
      with three-dimensional vector volume manometry of patients operated on according
      to Pena and matched controls demonstrated a significant improvement in the radial
      asymmetry index over the years and must be interpreted as a maturation process of
      the continence organ on a critical level.

PMID- 9931823
TI  - [Electron microscopy assessment of the effectiveness of intraoperative laser in
      reoperation of juvenile bone cysts].
AB  - The application of the ND-YAG-Laser in juvenile bone cysts prevents recurrencies.
      That can be put down to the fact that the laser has a deep action which destroys
      the organells of the cystic tissue up to 2-4 mm irreversibly. By this the whole
      cystic tissue is being destroyed and recurrencies are being prevented.

PMID- 9931824
TI  - [Long-term results after restorative proctocolectomy and ileoanal pouch in
      children with familial adenomatous polyps].
AB  - Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is considered
      the therapy of choice for the prophylactic treatment of FAP in adults, while
      straight ileoanal endorectal pull-throughs were often favored in children.
      However, our experience with five children undergoing an ileoanal J-pouch
      procedure under the age of 15 years (7-15) due to early onset of a severe
      symptomatic FAP phenotype suggests results which are superior to those after
      direct ileoanal anastomosis. Even after a primary straight ileoanal pull-through
      with local complications and a high defecation rate, secondary IPAA should be
      considered.

PMID- 9931825
TI  - [Significance of prenatal diagnosis in interdisciplinary treatment of
      sacrococcygeal teratoma].
AB  - The perinatal treatment of 23 infants with sacrococcygeal teratomas was recorded
      prospectively from 1990 to 1997, during which period 14 children (teratomas 6.9
      18 cm) could be followed throughout the whole pregnancy at our own perinatal
      department. There were three prenatal deaths (21 h-27 week of gestation) and two
      peripartal deaths (1 hydrops and 1 ruptured teratoma). Prenatal Doppler
      sonography allows appropriate selection of high-risk fetuses. The vital
      prognostic sign was developing fetal hydrops with associated umbilical vein
      pulsations, increased aortal flow and an increasing pulsatility index in der
      venous duct.

PMID- 9931826
TI  - [A method for reducing the risk of infection in newborn and premature infants
      with stomas].
AB  - Prematures and neonates with stomas have a high risk of developing sepsis by
      bacterial translocation, particularly when combined with parenteral nutrition. We
      studied a group of 35 newborns where split ileo- or jejunostomas were implanted
      in their first week of life. To prevent the development of a non-used distal
      bowel and a short bowel syndrome, the proximal bower content was transferred into
      the aboral stoma via the new continuous extracorporal stool transport (CEST)
      technique a few days after surgery. By using CEST the sepsis rate was reduced
      from 9 (without CEST) to only 0.8 cases of sepsis in 1000 days.

PMID- 9931827
TI  - [New approaches to tissue management in minimal invasive pediatric surgery].
AB  - Tissue management in minimally invasive surgery plays an important role in the
      indication for and feasibility of surgical interventions. Hemostasis and sealing
      of larger areas are possible with minimally invasive tissue gluing in liquid and
      bandage-bound form. For effective and efficient application of the precoated
      collagen fleece (TachoComb) a modularly constructed applicator (AMISA) was
      designed that is suitable for a wide range of indications in MIS and allows
      selective leak closure (SLC) in parenchymatous tissues with different lesions
      (Pneumothorax, Chylothorax, rupture of liver/spleen, biopsies, fistulae).

PMID- 9931828
TI  - [Minimal invasive, percutaneous ventriculostomy in therapy of severe
      craniocerebral trauma].
AB  - From May 1996 until April 1997 percutaneous CT-controlled ventriculostomy (PCV)
      was performed in 19 patients with severe traumatic brain injury and no indication
      for decompressive craniotomy. There was a significant reduction in the duration
      of the procedure compared to burr-hole ventriculostomy with no complications.
      Because of further advantage of PCV CT-controlling is the possibility of
      puncturing even very narrow ventricles.

PMID- 9931829
TI  - [The retrograde tibial nail in proximal tibial fractures--a biomechanical study].
AB  - Operative treatment of proximal tibial fractures required ORIF procedures with
      plate osteosynthesis. A cephalograde tibial nail provides the same mechanical
      stability as plate fixation. Closed reduction and soft tissue preservation are
      the advantages of this new technique.

PMID- 9931830
TI  - [Surgically-induced angiogenesis as basic principle in treatment ov
      hypovascularized wounds--the nutritive flap].
AB  - Chronic wounds of the lower extremity as a result of diabetes, arteriosclerosis
      and microangiopathy are of significant clinical relevance, as they result in
      immobilization, extended hospitalization and cost-intensive treatment. Via
      transfer of well-vascularized tissue onto chronic wounds as a free transplanted
      muscle flap, if necessary connected to a venous bypass, angiogenesis is induced
      and wound healing improved. This concept leads to nonamputational therapy.

PMID- 9931831
TI  - [Abdominal compartment syndrome after severe abdominal and/or pelvic trauma].
AB  - The incidence of the abdominal compartment syndrome (ACS) after severe abdominal
      and/or pelvic trauma is 3%. ACS occurs within hours and causes severe organ
      dysfunction. Decompressive emergency laparotomy restores this impaired organ
      function.

PMID- 9931832
TI  - [The Richard classic nail (intramedullary hip screw, IMHS) as unreamed
      intramedullary nail in osteosynthesis treatment of pertrochanteric fractures].
AB  - The treatment of 85 patients with pertrochanteric femoral fractures (average age
      82.3 years) with the Richards classic nail allowed full weight-bearing in 94.1%
      and unreamed implantation in 91.8%. In the follow-up period (11.2 months post
      operatively) few complications (1.2% infections, 1.2% cutting out) could be
      documented. The Sanders and Regazzoni score revealed that 66% of the patients
      reached their preoperative status again. Statistical analysis showed a negative
      influence of patient age and fracture type on the postoperative walking ability.

PMID- 9931833
TI  - [The free "emergency" rectus abdominis flap transfer for coverage of complex hand
      injuries].
AB  - Standard local flaps may be insufficient to cover extensive soft tissue defects
      of the upper extremity. To prevent further damage of exposed vital structures,
      early microsurgical free-flap transfer may be necessary. The rectus abdominis
      free muscle flap is introduced as a new and reliable procedure for emergency
      coverage of upper limb defects.

PMID- 9931834
TI  - [Instillation vacuum sealing--report of initial experiences].
AB  - Patients with acute (n = 13) or chronic (n = 14) infections were treated by the
      novel technique of instillation vacuum-sealing, which uses the PVA sponge as a
      drug-release system for antibiotic and antiseptic solutions. During a follow-up
      of 4.2 (3-14) months there was one recurrence of infection in a patient with
      chronic osteomyelitis.

PMID- 9931835
TI  - [New methods for effective prevention of thromboembolism in surgical medicine
      exemplified by trauma surgery].
AB  - Under conventional prevention (pharmacological and physical) of thromboembolism
      30-40% of surgical patients develop deep vein thrombosis (DVT). Mechanical
      methods significantly increase the efficacy of prophylaxis for thromboembolism:
      these include intermittent pneumatic compression, A-V impulse systems and ankle
      motion devices. For all trauma patients it is advisable that conventional
      prophylaxis of thromboembolism be supplemented with elements of mechanical
      prophylaxis in order to reduce the continuing high thrombosis rate significantly.

PMID- 9931836
TI  - [Regeneration of hyalin cartilage in the knee joint by treatment with autologous
      chondrocyte transplants--initial clinical results].
AB  - Treatment with autologous chondrocyte transplantation (ACT) leads to regeneration
      of hyaline cartilage. Since September 1996, 52 patients have been treated. Eleven
      patients were screened clinically and by MRI 18 months later. The biopsy specimen
      from the transplanted area showed formation of hyaline cartilage.

PMID- 9931837
TI  - [Etiology of cerebral perfusion disorder in patients with severe craniocerebral
      trauma].
AB  - In 53 patients with severe head injury, a decline of the cerebral perfusion
      pressure (CPP) was distinguished related to its cause, i.e., by a rise in
      intracranial pressure (ICP), a decline in the mean arterial pressure (MAP) or
      both. The mean Glasgow Outcome Scale (GOS) was 1.6 in patients with elevated ICP,
      3.8 in those with decreased MAP and 2.7 when impaired CPP was due to both. It is
      concluded that in cases of decreased CPP, elevated ICP is the main cause of
      secondary brain injury and poor outcome, independent of the circulatory
      condition, whereas an isolated decline in the MAP does not show any influence on
      functional outcome.

PMID- 9931838
TI  - [Dislocated proximal humerus fracture--results after stabilization with a double
      plate].
AB  - Between October 1995 und December 1997, 57 patients with displaced 2-, 3- and 4
      part fractures of the proximal humerus were treated by open reduction and
      internal fixation with two one-third tubular plates which were applied to the
      anterior and lateral aspect of the proximal humerus. For the follow-up evaluation
      shoulder function was assessed in 38 patients after an average of 16.8 +/- 4.2
      months using the Constant-score: 32% of the patients showed excellent, 37% good,
      21% satisfactory, and 10% unsatisfactory results. The high stability of this
      technique allows intensive physiotherapy in the early post-operative period and
      early reintegration in activities of daily living.

PMID- 9931839
TI  - [Improved postoperative prevention of thrombosis in trauma surgery by dose
      adjusted low molecular weight heparin based on TAT and D-dimer values].

PMID- 9931840
TI  - [Percutaneous minimal invasive autologous spongiosa transplantation].
AB  - In eight patients with delayed union or nonunion after 3 degrees open fracture of
      the tibia, a minimally invasive technique of autologous bone grafting was
      performed. Bone harvesting from the iliac crest and debridement of the fracture
      side were done percutaneous by using a 5.5 mm acromionizer without complications.
      In seven of eight patients complete fracture healing could be achieved (88%).
      Percutaneous autologous bone grafting can be recommended on limited bone defects
      in patients with nonunion or delayed union of the tibia and severe soft tissue
      damage in the lower leg.

PMID- 9931841
TI  - [Indirect traumatic diaphragmatic ruptures after blunt abdominal or thoracic
      trauma].
AB  - Traumatic diaphragmatic rupture after blunt thoracic or abdominal trauma is an
      indicator of serious associated injuries, but is itself often occult. Its
      diagnosis is still a challenge. In 14 consecutive patients with diaphragmatic
      rupture we developed a strategy for diagnostic work-up and therapy of
      diaphragmatic disruption. Ultrasound showed a sensitivity of 89% versus 50 and
      29% in chest X-ray and CT scan, respectively. Ultrasound of the diaphragm
      directly after admission and after stabilization of the trauma patient in order
      to find diaphragmatic disruption early is compulsory. Early treatment will avoid
      associated complications.

PMID- 9931842
TI  - [Importance of blade geometry for stability of fixation with short intramedullary
      nailing systems for the proximal end of the femur (gliding nail)].
AB  - Three biomechanical examinations of the double-T blade of the gliding nail were
      performed. Under alternating load, also after 100,000 cycles and 2000 N load, no
      instability occurred after gliding nail osteosynthesis. The best relationship
      between the introduction forces of the blade (1.771-1.329 N) and the extraction
      forces (1.474-477 N) was seen after glass pearl treatment of the blade surface.
      Displacement of the plate in a sow bone femor head after 1000 cycles at 1500 N
      was 1.0-4.00 mm for a double-T blade, but 4.0-8.0 mm for a 10 mm screw like the
      gamma-nail screw.

PMID- 9931843
TI  - [Endovascular reconstruction of the infrarenal abdominal aortic aneurysm-
      experiences with 3 endovascular stent prosthesis systems].
AB  - Seventeen patients were treated with endovascular stent grafts for AAA (seven
      Stentor, two Vanguard, three Talent and three EVT grafts). Intraoperative
      conversion to open procedure was necessary in three cases. One patient had open
      operation 24 h postoperatively for graft thrombosis. All patients had uneventful
      recovery. During follow-up (1-35 months) nine patients did not require
      reintervention. One patient had open repair for persistent endoleak: within 2
      months postoperatively one midgraft endoleak, one graft limb thrombosis and one
      groin infection were treated. We did not observe any late complications.

PMID- 9931844
TI  - [Endovascular infrarenal surgery of abdominal aortic aneurysm in selected
      patients: 3-years outcome and complication management].
AB  - We report a over 3-year single center experience with five different self
      expanding or ballon-expandable stent-graft devices used for aneurysm exclusion in
      the infrarental aorta. All devices appeared to offer a safe, efficacious, and
      minimally invasive means of excluding the aneurysms from circulation. Key to
      success is restrictive patient selection due to morphological criteria and
      improvements in surgical techniques and equipment to reduce the incidence of
      complications and endoleaks. At the moment, patients who opt for the endovascular
      method of repair should be aware that the minimally invasive technique carries
      the disadvantage of a higher failure rate compared to open surgery. Long-term
      results are required to establish selection criteria, especially for younger
      patients.

PMID- 9931845
TI  - [Value of stent-assisted aneurysm treatment].
AB  - The aim of this study was to compare the outcome of consecutive patients with
      abdominal aortic aneurysms treated by open operation and endoluminal procedure.
      Between October 1996 and April 1998 consecutive patients with abdominal aortic
      aneurysms underwent surgical repair. Of these, 50 patients had conventional open
      repair, and 48 patients were treated endoluminally. Follow-up was made by
      clinical examination in the operation group; the stent group was controlled by
      spiral CT and angiography 1, 3, 6, and 12 months after operation. No significant
      difference was found in the perioperative mortality rate between the open repair
      group and the stent group. This study suggests that the endovascular procedure is
      safe and results in a shorter length of hospital stay and a shorter length of
      intensive care unit stay. As there are no long-term results, the endoluminal
      method requires a careful follow-up.

PMID- 9931847
TI  - [Varicose and ascending thrombophlebitis--surgical planning for emergency
      crossectomy by duplex ultrasound].
AB  - Ascending thrombophlebitis of the superficial leg veins is known to pass into the
      deep veins, causing an embolism to develop. Duplex ultrasonography has been shown
      to be a reliable technique for the evaluation of superficial venous thrombosis.
      If progression is noted, crossectomy proved to be effective in preventing passage
      of thrombi into the deep veins.

PMID- 9931846
TI  - [Ascending varicose vein phlebitis--classification and therapy].
AB  - Ascending varicophlebitis can cause pulmonary embolism by entering the deep
      venous system. Classification into four stages permits a differentiated
      therapeutic strategy: if the thrombus reaches or enters the deep venous system,
      immediate surgery consisting of crossectomy, resection of the saphenous vein,
      radical excision of all varicosed veins and ligature of insufficient perforating
      veins are indicated.

PMID- 9931848
TI  - [Early plastic coverage increases rate of varicose ulcer healing].
AB  - Treatment of venous ulcer remains a major clinical problem. In a retrospective
      study including 83 patients with venous leg ulcers, we demonstrated increased
      healing rates in patients under 60 years of age and ulcers treated by mesh graft.

PMID- 9931849
TI  - [Do patients with changes in the vertebral arteries have an increased risk in
      carotid artery obliteration?].
AB  - There was no difference between the groups investigated in terms of the
      preoperative neurological stages. In patients with VA involvement, both the 30
      day mortality rate (p < 0.01) and the long-term survival rate (p < 0.01) were
      significantly poorer. In the study group, the incidence of shunt procedures was
      three times as high as in the control group (p < 0.01).

PMID- 9931850
TI  - [Short distal venous bypass for saving the extremity diabetic foot].
AB  - If inflow to the distal superficial or popliteal artery is not compromised in
      diabetic patients with critical leg ischemia short distal vein bypass grafts can
      be constructed to tibial or foot arteries. By restoration of foot perfusion,
      durable limb salvage with only minor tissue loss can be achieved in most
      patients. Postoperative progression of inflow artery disease is uncommon.

PMID- 9931851
TI  - [Combination of profundaplasty and pharmacotherapy in stage III/IV peripheral
      arterial occlusive disease].
AB  - This prospective randomized study shows that adjuvant 3-week i.v. PGE1 treatment
      substantially improves the short-term results in patients undergoing
      profundaplasty. Compared with placebo, PGE1 approximately doubles the number of
      patients returning from stage III/IV to stage IIb of PAOD. Five years after
      surgery, the outcome with respect to limb salvage and patient survival rate was
      significantly better in patients additionally treated with PGE1.

PMID- 9931852
TI  - [A new concept for substitutes in vascular surgery].
AB  - In a tissue engineering approach to develop vascular grafts without disadvantages
      such as early thrombosis, neointimal hyperplasia, the inability to grow, aneurysm
      formation, as well as life-long anticoagulation, decellularized matrix tubes
      which were obtained by enzymatic cell extraction from a porcine aorta were seeded
      with human endothelial cells in vitro. This procedure led to completely
      biological vascular grafts with good handling qualities and sufficient burst
      strength, presumably suitable for implantation in the arterial circuit.

PMID- 9931853
TI  - [Functional results after bilateral thoracoscopic lung volume reduction surgery
      in emphysema].
AB  - We investigated functional results, complications and survival of patients
      undergoing bilateral video-assisted thoracoscopic (VAT) lung volume reduction
      surgery (VRS) for severe, diffuse pulmonary emphysema [FEV1 28 +/- 0.8 (% pred.),
      RV/TLC 0.65 +/- 0.01, 12' walking distance 499 +/- 21 (m)]. From January 1994 to
      March 1998, 106 of 286 candidates were operated, 85 patients (mean age 64, range
      38-78 years, 30 females) fulfilled the study criteria and were included in the
      prospective study. Hyperinflation decreased to an RV/TLC ratio of 0.51 +/- 0.01
      after 3 months and 0.55 +/- 0.02 after 24 months, FEV1 increased to 43 +/- 1.6 (%
      pred.) after 3 months and 35 +/- 2.3 (% pred.) after 24 months, and the 12'
      walking distance was 687 +/- 29 (m) 3 months postoperative and 626 +/- 44 (m)
      after 24 months.

PMID- 9931854
TI  - [Detection of unexpected extrathoracic metastases in preoperative staging of non
      small-cell bronchial carcinoma (NSCLC) with positron emission tomography (PET)].
AB  - Accurate staging of non-small cell lung cancer (NSCLC) is essential for
      subsequent treatment. This study was designed to evaluate the value of FDG-PET in
      detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC
      qualifying for surgical treatment based on conventional staging. One hundred
      patients with stage IIIa or less were included and underwent clinical evaluation,
      chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests.
      If clinical signs of EM were present additional diagnostic methods, were applied.
      A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed
      histologically or radiologically. Unknown ETM were detected in 13 patients (14%)
      at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients
      with NSCLC otherwise eligible for surgery. Fourteen percent of patients were
      understaged.

PMID- 9931855
TI  - [Video-assisted thoracoscopy for effective palliation of malignant pleural
      effusion. Pleurodesis--pleuroperitoneal shunt].
AB  - Dyspnea and reduced physical capability mean a significant reduction in quality
      of life of patients with advanced tumor disease. Video-assisted thoracoscopic
      talc poudrage or alternatively placement of pleuroperitoneal shunts were
      retrospectively evaluated as procedures for definitive palliation.

PMID- 9931857
TI  - [Mid-term results of scapho-trapezio-trapezoid arthrodesis in aseptic semilunar
      bone necrosis stage IIIa/b].
AB  - The mid-term results of 20 cases of Kienbock's disease treated with
      scaphotrapezio-trapezoid arthrodesis with an average follow-up period of 25
      months between 1993 and 1997 are presented. Clinical results were good with
      regard to pain, grip strength and range of motion; the results with regard to the
      DASH questionnaire were very good. It can be concluded from this study that STT
      arthrodesis is a useful procedure for the treatment of Kienbock's disease in
      stage III.

PMID- 9931856
TI  - [Does tissue perfusion after free microvascular tissue transplantation stay
      autonomous?].
AB  - In a prospective study including 60 patients after free latissimus dorsi transfer
      (FLDT) to the lower leg, we found persistence of pedicle blood flow up to 10
      years postoperatively. After uncomplicated FLDT the pedicle supported the flap in
      all cases, whereas after complicated FLDT (hematoma, thrombosis, infection) we
      found only 50% of all flaps autonomously perfused by the vascular pedicle.

PMID- 9931858
TI  - [Genetic methods in experimental xenogenic nerve transplantation].
AB  - The ready availability of xenografts and the promising results of genetic
      engineering both may offer new methods in peripheral xenotransplantation. FK506
      and RS61443 are able to prolong survival of nerve xenografts. The incorporation
      of adenoviral sequences in xenogeneic tissues is possibly a new option for
      decreasing the toxicity of immunosuppressive drugs and immunogenicity of grafts.

PMID- 9931859
TI  - [Surgical therapy of gynecomastia and its results].
AB  - The objective of our study was to evaluate the factors which lead to operative
      therapy of gynaecomastia for cosmetic or diagnostic reasons and to assess the
      postoperative results. 100 patients with gynaecomastia underwent subcutaneous
      mastectomy (n = 98) or total mastectomy for gynaecomastia through different
      incisions, with subjectively satisfactory results in 93% of all patients,
      although cosmetically unsatisfactory results occurred in more than 50% of all
      patients. Although the surgical objective is achieved by current operative
      therapy, many patients experience cosmetically unsatisfactory results, which
      demands the evaluation of other operative strategies with a potentially higher
      rate of cosmetically adequate results.

PMID- 9931860
TI  - [Bridging long bone and joint defects with allogeneic vascularized transplants].
AB  - Three patients with large osseous defects following trauma and infection received
      vascularized allogeneic femoral diaphyses and five patients vascularized
      allogeneic total knee joints. From the surgical aspect these transplantations are
      technically feasible. The remaining problems are of immunological nature; at
      least in patients with allogeneic synovial joints, lifelong immunosuppression
      seems to be currently unavoidable.

PMID- 9931861
TI  - [Pre- and postoperative ultrasound in reconstruction of finger flexor tendons in
      zone 2].
AB  - Twenty-five patients with 31 zone 2 flexor tendon injuries were evaluated
      prospectively by means of high-resolution ultrasonography and clinically. Results
      were assessed according to Buck-Gramcko's Strickland's, LMS and TAM score.
      Ultrasonic findings led to individual modifications (abbreviation or
      prolongation) of postoperative hand therapy and were helpful in decision making
      for secondary surgery like tenolysis or secondary repair.

PMID- 9931862
TI  - [Dupuytren disease--formal pathogenesis without contraction and a new surgery
      concept].
AB  - The palmar fibromatosis holds the finger in the flexed position--extension
      inhibition rather than contraction. According to this extrinsic concept, only a
      passive, secondarily reactive effect can be attributed to the palmar aponeurosis.
      Out of 72 hands examined 5 or more years after an operation in which the
      aponeurosis had been left intact, 47% proved to be clear of disease.

PMID- 9931863
TI  - [Simultaneous or stepwise procedure in combined minimal invasive and conventional
      operation methods in vascular surgery].
AB  - Long-term results of femoral angioplasty and stenting are not as successful as
      open surgical procedures. Transfemoral retrograde recanalisation of the iliac
      vessel by semiclosed endarterectomy is a low-invasive procedure. Certainly the
      outcome is characterised by a number of early occlusions caused by dissections or
      remaining intimal flaps. Recent advances in endovascular management of occlusive
      disease have changed the situation. Intraoperative control of lumen by angioscopy
      and removal of occlusive material via TV-monitored endoscopic manipulation has
      induced better results of endarterectomy. In addition to this more effective
      recanalisation, the proximal intimal step, mostly at the level of the iliac
      bifurcation, is managed by intraoperative balloon dilatation and stenting. This
      combined approach has reduced the necessity of reoperation by about 15%. The
      cumulative 5-year patency rate for this combined procedure is 88%.

PMID- 9931864
TI  - [Is the type of vessel wall change a risk factor in implantation of prostheses in
      the aortofemoral segment? Dilatative versus obliterating arteriopathy].
AB  - The question of what effect role obliterative vessel disease has on postoperative
      outcome was analysed with the help of uni- and multivariate analysis. The
      univariate analysis showed significantly more preoperative risk factors in
      patients with obliterative vessel disease. Our multivariate analysis found three
      independent factors: ASA class, age, duration of surgery. Obliterative vessel
      disease seems to be a disadvantageous factor, but may be influenced by
      preoperative existing risk factor.

PMID- 9931865
TI  - [Allogenic arterial transplants as aorto-iliaco-femoral vascular replacement in
      prosthesis infection].
AB  - From June 1996 to February 1998 10 patients with aorto-femoral graft infection
      were treated in our department. In all cases infected vascular grafts were
      removed and in situ cryopreserved arterial allograft was inserted. Two patients
      died on the 1st and the 17th postoperative day due to septic shock or heart
      infarction. In all of the eight survivors infection could be eradicated and
      during the follow-up period they were in good condition.

PMID- 9931866
TI  - [A comparative study of minimal invasive harvesting of vena saphena magna
      segments].
AB  - From July 1997 to February 1998 we performed either minimally invasive or
      endoscopic saphenous vein harvesting in 55 patients and compared the results with
      those of 46 patients after conventional saphenous vein harvesting. Minimally
      invasive and endoscopical vein harvesting can be safely performed after a longer
      learning curve. Patients after minimally invasive and endoscopical saphenous vein
      harvesting showed fewer wound healing problems and better cosmetic results than
      after conventional vein harvesting.

PMID- 9931867
TI  - [Control of the patency of coronary artery bypasses with contrast enhanced
      magnetic resonance angiography].
AB  - Contrast-enhanced 3D magnetic resonance angiography (MRA) has the potential for
      being a reliable method for CABG visualization and CABG patency determination in
      early postoperative period. 3D reconstruction was helpful in delineating CABG
      course and in several cases in detecting stenosis of coronary arteries. Compared
      to coronary angiography MRA is a non-invasive examination technique without
      iodine contrast medium and X-ray and is practicable in 30 min with minimal risk
      and low costs.

PMID- 9931868
TI  - [Morbidity and tumor control in limb-saving resection with intraoperative
      radiotherapy in a multimodality therapy concept in soft tissue sarcoma].
AB  - This study evaluates limb-saving surgery (LSS) combined with intraoperative
      radiotherapy (IORT) and external beam radiotherapy (EBRT) for extremity sarcoma.
      Prospectively gathered data was analyzed for 50 patients. Advanced stages (UICC
      IIB-IIIB) predominated (80%) and 50% of the tumors were recurrent. Early local
      morbidity amounted to 32%, including wound infection (6), skin necrosis (3),
      hematoma (3) and others (4). Late morbidity of 10% consisted of a fracture, a
      fibrosis, two chronic lymphedemas and a neuropathy. One patient died (pulmonary
      embolism). Local control was obtained in 91% with an overall 3-year survival rate
      of 81% in cases treated with curative intent (follow-up 29 months). No survival
      benefit was found for patients with microscopically clear margins; however, local
      failure occurred less frequently (p = 0.02). Our results support the use of LSS
      with IORT and EBRT for extremity sarcoma and emphasize the importance of the
      surgical margin.

PMID- 9931869
TI  - [Secondary resection of soft tissue sarcomas within the scope of a multimodality
      therapy concept].
AB  - We treated 95 patients with primary soft tissue sarcoma of the extremities or
      trunk between 1988 and 1995, who were operated on initially elsewhere and their
      tumors were supposed to be excised completely. We performed a primary re-excision
      in all patients and found residual tumor in 46%. After a median follow-up of 61
      months, 16 patients developed a local recurrence and 6 patients died due to the
      tumor disease. Primary re-excision is therefore indicated in most cases where the
      histology report of an assumed benign tumor reveals malignancy.

PMID- 9931870
TI  - [Does sentinel node biopsy (SNB) solve the problem of elective lymph node
      excision in malignant melanoma?].
AB  - Elective lymph node dissection in high-risk melanoma has been hotly debated for
      years. The technique of sentinel node (SN) biopsy may be a solution to the
      problem. Consequently, radical lymph node dissection is restricted to patients
      with an actual metastatic involvement of the SN (20-25%). The use of a hand-held
      gamma probe increases accuracy of SN detection.

PMID- 9931871
TI  - [Primary malignant tumors of the sacrum].
AB  - The oncological and functional results of 16 patients with primary malignant
      sacral tumors (12 chordomas, 3 chondrosarcomas, 1 fibrosarcoma) during the past
      decade are reported. Dorsal approach was used in 10 cases, ventral or combined
      ventrodorsal procedure in 5 cases; in 1 case only biopsy was taken. Amputation of
      rectum with colostomy was necessary in 9 cases, ileosacral stabilization in 2
      cases. Eight patients died, 5 of the disease and 3 of complications, with a mean
      survival time of 25.8 months. Local recurrence occurred in 4, distant metastases
      in 3 cases. Six of the 8 survivors--mean survival is 59 (21-112) months--showed
      good or excellent functional results according to the Enneking score system.
      Local complications, mostly wound healing problems, were observed in 9 (56%),
      neurological disorders in respect of the resected sacral nerve roots in 11 (68%)
      cases. The oncological and functional results after resection of primary
      malignant sacral tumors, especially of chordomas, justify radical surgical
      procedures sacrificing the sacral nerve roots.

PMID- 9931872
TI  - [Magnetic resonance tomography in diagnosis of vascular infiltration in malignant
      pancreas tumors].
AB  - This study was undertaken to evaluate the accuracy of magnetic resonance
      angiography (MRA) in assessing venous or arterial infiltration in pancreatic
      cancer. In 90 patients MRA showed a sensitivity of 81.1%, a specificity of 90.2%
      and an accuracy of 85.9% in predicting venous infiltration and a sensitivity of
      81.8%, a specificity of 90.7% and an accuracy of 88.1% in predicting arterial
      infiltration. From these data we conclude that MRA is an accurate method for
      detecting vascular infiltration in pancreatic cancer.

PMID- 9931873
TI  - [Value of diagnostic laparoscopy in primary malignant liver tumors].
AB  - The advent of new imaging modalities such as CT-AP and MRT has markedly improved
      the diagnosis and staging of primary liver tumors and will change the diagnostic
      impact of laparoscopy. Diagnostic laparoscopy in this retrospective study was not
      found to add information in regard to tumor staging and resectability, and there
      was no clear benefit by avoiding diagnostic laparotomies when all imaging and
      biopsy techniques available were used preoperatively. Therefore, we advocate the
      use of diagnostic laparoscopy only in selected cases suspicious for superficial
      small tumor lesions and cirrhosis with impact on the treatment modality.

PMID- 9931874
TI  - [Technique, risks and results of additional portal vein resection in surgical
      therapy of proximal bile duct carcinoma].
AB  - The infiltration of the portal vein is not considered an absolute
      contraindication for resection therapy of proximal bile duct carcinomas. Portal
      vein resection and reconstruction may be performed without additional
      perioperative risk after hilar resection and hepatectomy. The resected hepatic
      vein is a suitable material for portal vein reconstruction. The median survival
      of patients with additional portal vein resection is comparable with patients
      without vascular infiltration in the same tumor stage.

PMID- 9931875
TI  - [Extended partial Kausch-Whipple duodenopancreatectomy by resection of tumor
      infiltrated vascular segments].
AB  - The experience with standard Kausch-Whipple procedure is reviewed and compared
      with partial duodenopancreatectomies extended by partial resection of the portal
      vein. Perioperative morbidity has decreased to below 5% and survival rates with
      and without vessel resection are not significantly different. Therefore,
      infiltration of mesentericoportal vessels is not a contraindication for Kausch
      Whipple procedure.

PMID- 9931876
TI  - [Radical surgery in cystadenoma of the pancreas--long-term experiences with 35
      patients].
AB  - We report on 15 patients with mucinous and 19 patients with serous cystadenoma of
      the pancreas. Cystadenomas were more common in female patients (22/12), and CT
      was the most sensitive diagnostic tool. There was no mortality in the short or
      the long term (median 6 years); however, mucinous cystadenomas tend to recur when
      not treated by radical resection.

PMID- 9931877
TI  - [Locoregional and systemic therapy of advanced pancreatic carcinoma].
AB  - Pancreatic cancer has a very poor prognosis despite surgical resection or
      chemotherapy. For patients with a pancreatic cancer stage III or IV, locoregional
      or systemic chemotherapy is often the only chance for treatment. In our opinion,
      locoregional treatment is currently the best concept.

PMID- 9931878
TI  - [Hormone therapy of postoperative recurrent pancreatic carcinoma with octreotide
      and tamoxifen].
AB  - In a prospective trial a combination of octreotide and tamoxifen was evaluated
      for its effect on tumour recurrence of R0-resected pancreatic carcinoma. Compared
      to the control group (n = 14), which was treated according to "best supportive
      care", the median survival times for the octreotide-tamoxifen group (n = 14) were
      7 and 3.5 months respectively. In the octreotide-tamoxifen group patients
      suffered less from nausea, pain and fatigue (p < 0.05). Furthermore, there was a
      benefit of octreotide-tamoxifen therapy for global life quality.

PMID- 9931879
TI  - [Isolated hypoxic perfusion with mitomycin C confers no benefit for patients with
      advanced pancreatic carcinoma].
AB  - Since therapy options in the treatment of advanced pancreatic cancer are rare,
      the present study has investigated whether patients with advanced pancreatic
      cancer may profit from isolated hypoxic perfusion (IHP) of the abdomen with
      mitomycin C. None of the 17 treated patients responded to IHP with mitomycin C,
      and the survival time corresponded to that of untreated patients. On the basis of
      these results, this procedure should no longer be used as treatment for patients
      with advanced pancreatic cancer.

PMID- 9931880
TI  - [Preoperative staging of stenosing esophageal carcinoma--prospective comparison
      of mini-endosonography with conventional endosonography].
AB  - Staging of esophageal malignancies can easily and safely be performed with
      ultrasonic miniprobes. Unlike large-diameter ultrasonic instruments, miniprobes
      may pass even high-grade malignant esophageal strictures without prior bouginage.
      Image quality and resolution of miniprobe sonography exceeds that of conventional
      endosonography, thus achieving higher accuracy rates for T staging, while those
      for N staging have found to be similar. As miniprobe sonography is able to
      improve patients' convenience and security and is highly cost effective compared
      to conventional endosonography, miniprobe sonography appears to be a valuable
      addition to the staging armamentarium in esophageal carcinoma.

PMID- 9931881
TI  - [Achalasia and carcinoma of the esophagus: incidence, prevalence and prognosis].
AB  - Although the prevalence of patients with achalasia developing an esophageal
      carcinoma is low the risk is nearly 140-fold; there is no difference in prognosis
      between patients with achalasia-carcinoma and those with esophageal cancer
      without achalasia. We propose a follow-up with biennial endoscopies after 15-20
      years of known achalasia. This is accordance with a recent consensus conference,
      which accepted the recommendation of the American Society of Gastrointestinal
      Endoscopy [3]. In doubtful findings we recommend brush cytologies and/or
      biopsies, especially if there should be a recurrence of "old symptoms" or the
      appearance of "new difficulties" which suggest the possibility of a malignant
      growth.

PMID- 9931882
TI  - [Prognostic significance of apoptosis inducers/inhibitors in stomach carcinoma
      with/without adjuvant intraoperative radiotherapy (IORT)].
AB  - Several studies have tried to improve the surgical results after resection for
      gastric cancer by different adjuvant therapy protocols, including intraoperative
      radiotherapy (IORT). Since 1990 we have performed a randomized, prospective trial
      comparing surgery alone and surgery plus adjuvant IORT to evaluate the role of
      adjuvant intraoperative radiotherapy in the treatment of curative resected
      gastric carcinomas. In the present study, p53, bcl-2 immunoreactivity and DNA
      fragmentation as a typical marker of apoptosis were determined to investigate the
      predictive value of apoptosis-related factors and the observed response to
      radiotherapy. Preliminary data indicate that patients with tumors containing
      increased numbers of apoptotic tumor cells might derive benefit from adjuvant
      IORT.

PMID- 9931883
TI  - [Results of intraperitoneal active charcoal-mitomycin C therapy of stomach
      carcinoma with serosa invasion].
AB  - Patients with gastric carcinoma and serosal invasion were randomized into a
      "treatment" or "control" protocol after R0 resection ("prophylactic group", n =
      45) or palliative resection without cytoreductive surgery in cases with localized
      peritoneal seeding ("therapy group", n = 19). The results of a planned interim
      analysis after 5 years indicate that MMC-CH therapy causes little systemic
      toxicity but enhances the rate of intraabdominal infections (9/33 vs. 2/31, p <
      0.01) and reoperations (5/33 vs 0/31, p < 0.05). The preliminary survival
      analysis shows a possible prognostic effect following R0 resection after 24
      months (p < 0.05) and 36 months (p < 0.07), but no benefit for the palliative
      procedures, which caused the withdrawal of the "therapy" study arm.

PMID- 9931884
TI  - [Value of magnetic resonance tomography in preoperative staging of stomach
      carcinoma].
AB  - The value of MRI as a preoperative staging procedure in stomach carcinomas
      compared to CT and endosonography was examined in a prospective study and
      correlated with the pathohistological results. MRI showed better correlation with
      the pathohistological evaluation at the T3, T4, N and M stage than the other two
      test procedures. MRI is thus a suitable staging procedure for stomach carcinomas.

PMID- 9931885
TI  - [Perioperative immunomonitoring in stomach carcinoma--useful diagnostic
      supplementary test for detecting patients at risk for complications?].
AB  - Early detection of postoperative complications before clinical signs occur seems
      to be possible by perioperative immunologic monitoring. Patients with
      insufficiency of the anastomosis after gastrectomy showed a significant increase
      in anti-inflammatory cytocine IL-10 already 4 h after operation.

PMID- 9931886
TI  - [Diagnostic and therapeutic strategies in local recurrence of stomach carcinoma].
AB  - Despite clear margins at the time of resection, 7 to 20% of the patients
      experience local recurrence of the primary stomach tumor. Intraluminal recurrence
      is rare but curable in 50% of the cases without distant metastases. Extraluminal
      recurrent gastric cancer comprises the typical pattern of recurrence and cannot
      be removed in most of the patients. Predisposing factors that favor the
      development of recurrent tumors are: higher tumor stages, extended lymph node
      involvement, tumor grades 3 and 4, diffuse type according to Lauren's
      classification, and intraoperative perforation of the primary gastric carcinoma.

PMID- 9931887
TI  - [Does the pouch modify food transit after gastrectomy?].
AB  - A prospective, randomized study of patients with gastric cancer was performed to
      examine whether or not the jejunal pouch interposition between esophagus and
      duodenum after gastrectomy is of importance. At fixed postoperative times,
      standardized scintigraphic measurements were performed; the quality of life was
      evaluated by the EORTC quality of life questionnaire. Our findings suggest that
      interposition of a jejunal pouch reservoir between esophagus and duodenum may be
      due to a prolonged transit time and a better quality of life.

PMID- 9931888
TI  - [Beta-catenin expression and its significance for metastasis in curatively
      operated rectum carcinoma].
AB  - Two selected groups of 77 patients each (matched for age, sex, UICC stage and
      year of surgery) were compared. All patients were curatively operated on for
      rectal cancer by surgery alone. All remained locally disease-free, differing only
      in distant metachronous metastatic spread. beta-Catenin expression was
      investigated using immunohistochemical methods. Overexpression of nuclear beta
      catenin was not correlated with disease-free survival or distant metachronous
      metastasis. Thus, this potential oncogen cannot be used as a prognostic marker in
      rectal cancer. Additionally, in four cases of intense nuclear staining, after DNA
      isolation and sequencing of exon 3, which encodes for the GSK-3 beta
      phosphorylation site, no mutations could be detected.

PMID- 9931889
TI  - [Fractionated, interstitial postoperative HDR-/PDR-brachytherapy with
      intraoperatively placed probes--initial experiences with a new radiotherapy
      modality in treatment of recurrent or non-resectable colorectal carcinomas].
AB  - Twenty-eight patients with recurrent (82.1%) and/or noncuratively resected
      (71.4%) colorectal cancer underwent fractionated interstitial BT (20.1 Gy) by
      using median 5.6 (3-11) afterloading tubes placed directly on the tumor bed
      intraoperatively. HDR/PDR BT started 2-3 weeks after multivisceral resection
      (50%) and was combined with external beam radiation therapy in 96% and with
      chemotherapy (5-FU/Leucoverin) in 86% of the patients. Though the R0-resection
      rate before BT was only 28.6% multimodality treatment resulted in a local tumor
      control rate of 64.3%, a survival rate of 53.6%, and a tumor-free survival rate
      of 42.9%, in an average of 19.8 months (2-43 months) after BT.

PMID- 9931890
TI  - [Prognostic factors after multi-visceral resection of colorectal carcinomas].
AB  - The 50%-5-year survival rate after R0-resection confirms that multivisceral
      resection is warranted for locally advanced colorectal cancer. The data also
      demonstrate that long-term survival is significantly influenced by the surgical
      technique (blood loss).

PMID- 9931891
TI  - [Surgical rectal obstruction--change in treatment over the last 10 years].
AB  - The authors retrospectively analyzed 523 patients with large bowel obstruction
      (LBO): 126 (24.09%) right-sided (RSLBO) and 397 (75.91%) left-sided (LSLBO),
      treated at the Emergency Medicine Institute "N. I. Pirogov" in Sofia. For the
      period 1988-1997, a trend toward more radical and aggressive surgery is shown:
      compared to a previous period (1964-1983) the one-time operations (partial,
      subtotal and total colectomy with primary anastomoses) are becoming standard
      operations in RSLBO as well as in LSLBO. A classification based on objective
      clinical, X-ray and intraoperative findings is considered in the diagnostic and
      therapeutic algorithm of the LSLBO.

PMID- 9931892
TI  - [Early postoperative complications after different methods of intestinal
      reconstruction in deep anterior rectum resection--a prospective study].
AB  - For the first period after low anterior resection and total mesorectal excision
      for rectal cancer, the colonic J-pouch is superior to the straight or
      lateroterminal anastomosis. Despite the simple technique and short stretch of
      sutures, the LTA is unsuitable due to the high postoperative morbidity and
      because the reconstruction functions poorly. If the expected anastomis is below 6
      cm from the anal verge, i.e. 4 cm above the sphincter muscle, the colonic J-pouch
      is recommended.

PMID- 9931893
TI  - [Adjuvant radiochemotherapy with 5-FU and folinic acid in Dukes stage B and C
      rectum carcinoma: an interim analysis].
AB  - In a prospective multi-institutional German adjuvant trial patients with
      curatively resected rectal cancer (Dukes B or C) were randomly assigned to
      receive postoperative radiotherapy (50.4 Gy) and either 12 or 6 cycles of 5
      fluorouracil and medium-dose folinic acid. Our preliminary results of the interim
      analysis, based on 206 patients, indicate that this adjuvant therapy is well
      tolerated by the patients and a prolonged chemotherapy over 12 months has no
      advantage over 6 months of chemotherapy. The relatively high rate of tumor
      recurrence (30.7%) after a median follow-up of 29.3 months in this trial
      emphasizes the need for dose intensification planned for a further trial.

PMID- 9931894
TI  - [Results of interdisciplinary sacrum resection in sacral recurrence of rectal
      carcinoma].
AB  - The authors present a retrospective analysis of 12 consecutive patients
      surgically treated with curative intention for recurrent rectal cancer involving
      the sacrum. After radical partial sacral resection--extended resection in seven
      cases--the operative mortality rate was zero, postoperative long-term survival
      was reached in 17%, while effective palliation of pain was achieved in all cases.
      Nevertheless, 50% did not survive more than 1 year after the operation. The
      overall mean survival time was 22 months. Sacral recurrence can be resected
      safely and potentially curatively after careful patient selection.

PMID- 9931895
TI  - [Comparative diagnosis of locally advanced rectal carcinoma after preoperative
      therapy].
AB  - Locally advanced rectal carcinomas were increasingly treated by preoperative
      combined radiochemotherapy. Alterations of the rectal wall and the lymph nodes
      that were caused by the treatment make the assessment of the success of the
      therapy during the preoperative staging extremely difficult. Methods such as
      endorectal ultrasound, CT and MRI used for the estimation of the depth
      infiltration of the tumor achieved an exactness of only approximately 50%. It is
      thus essential to develop new criteria for the assessment of the success of the
      therapy.

PMID- 9931896
TI  - [Modification of surgical strategy in HNPCC by molecular and clinical aspects].
AB  - Because of the positive correlation between Amsterdam criteria and positive MSI
      analysis, a subtotal colectomy with ileorectal anastomosis seems to be indicated
      in patients with positive Amsterdam criteria to eliminate the high risk of
      metachronous colon cancer. In patients with an identified mutation in one of the
      known mismatch repair genes, a subtotal colectomy is indicated as well. In
      patients with positive Bethesda criteria, apart from the Amsterdam criteria, a
      subtotal colectomy seems only to be indicated if a positive MSI analysis is
      available.

PMID- 9931897
TI  - [Heidelberg polyposis register. Experiences with ileoanal pouch in familial
      adenomatous polyposis coli (FAP): the ileoanal anastomosis problem zone].
AB  - Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is the
      therapy of choice for the prophylactic treatment of FAP. Despite maximal
      radicality, we frequently observed remaining rectal mucosa and in some cases even
      adenomas at the pouch-anal anastomosis. Therefore, we changed our postoperative
      care by adding a yearly proctoscopy to regular pouchoscopies.

PMID- 9931899
TI  - [Prognostic differences in primary malignancies of the small intestine].
AB  - Malignant small bowel tumours are rare, with about 320 deaths every year due to
      metastases. Tumours of differing histologic entitites (adenocarcinomas,
      leimyosarcomas, non-Hodgkin, lymphomas, carcinoids) are detected at late stages
      of the disease because of non-specific symptoms. Valuable diagnostic means are
      small bowel enema, intestinoscopy and abdominal CT/ultrasound. Five-year survival
      rates are poor for carcinomas (21%), for sarcomas (37%), lymphomas (44%) and best
      for carcinoids (100%). Surgical options are poor for carcinomas with a high
      number of R2 resections and bypass operations. Multivisceral surgery is
      beneficial for sarcomas and lymphomas, followed by local radiation therapy or
      chemotherapy.

PMID- 9931898
TI  - [Tikhoff-Linberg interscapulothoracic resection in extra-compartmental tumors of
      the shoulder girdle].
AB  - Ninetten consecutive patients with bone and soft tissue tumors of the shoulder
      girdle were treated with interscapulothoracic resection (Tikhoff-Linberg
      procedure) over a 10-year period. Twelve patients were alive with no evidence of
      disease at a mean follow-up of 6.3 (1-11) years and one patient is alive with
      local recurrence and pulmonary metastases after 15 months. Six patients died due
      to pulmonary metastases. Despite these complications, the Tikhoff-Linberg
      procedure proved to be a valuable operation for extended tumors of the shoulder
      girdle in terms of functional and oncological outcome and is clearly superior to
      forequarter amputation.

PMID- 9931900
TI  - [Current therapeutic strategy in primary intestinal non-Hodgkin's lymphoma].
AB  - Of all surgical interventions of intestinal non-Hodgkin's lymphomas 58% (15 or 26
      patients) are performed in an emergency situation. In 42% of cases, examination
      by ultrasonography, endosonography, intestinoscopy. Sellink's enema, thoracic,
      abdominal/pelvic CT and bone marrow puncture could determine the stage
      preoperatively. This could also be done by examining the regional and
      juxtaregional lymph nodes or performing a liver biopsy intraoperatively. Crucial
      for the therapy is in all cases the adequate staging even in emergency
      situations. Only special knowledge of the intestinal non-Hodgkin's lymphoma can
      lead to the necessary stage-adapted multimodal therapy-
      operation/irradiation/chemotherapy.

PMID- 9931901
TI  - [Prognostic factors in combined radiochemotherapy of the anal canal carcinoma].
AB  - Combined radiation and chemotherapy is an effective treatment for all stages of
      carcinoma of the anal canal. Abdominoperineal resection is reserved for patients
      with incomplete regression of tumor or recurrent carcinoma.

PMID- 9931902
TI  - [Prognostic factors and subsequent indications for surgery in pulmonary
      metastasis of renal cell carcinoma].
AB  - Between 1975-1996, 39 patients underwent resection of pulmonary metastases from
      renal cell carcinoma. Multivariate analysis (COX model) for survival of
      preoperative risk factors showed that time of diagnosis (syn-/metachronous) of
      the metastases (p = 0.05) and the number of metastases (p = 0.01) were of
      prognostic significance. It is concluded that metastasectomy in patients with not
      more than six metachronous metastases after renal cell carcinoma has significant
      benefit and in cases of synchronous metastases or more than 6 pulmonary
      metastases indication for resection should be restricted.

PMID- 9931903
TI  - [Malignant melanoma of the skin: is there a curative surgical approach in
      locoregional metastasis?].
AB  - Between 1969 and 1993 at the Surgical University Hospital of Erlangen, 273
      patients with synchronous or metachronous locoregional metastases were operated
      on with curative intent; patients with distant metastases at the time of primary
      operation or first recurrency were excluded. In 216 patients (79.1%) a curative
      operation was performed and we achieved a statistically significant improvement
      of the 5-year-survival rate compared with those patients treated only
      palliatively (39.3% vs. 21.1%, p < 0.01). If regional lymph node metastases
      occur, the prognosis becomes significantly worse (5-year survival rate 45.2% vs.
      25.2%, p < 0.01); hyperthermic isolated limb perfusion shows a high importance in
      the treatment of locoregional metastases and the 5-year survival rate of patients
      treated with hyperthermic limb perfusion is significantly higher (39.0 vs. 64.2%,
      p < 0.05).

PMID- 9931904
TI  - [Peritonectomy and intraperitoneal chemotherapy--new methods in multi-modality
      therapy of peritoneal carcinosis].
AB  - In patients with peritoneal carcinomatosis, multimodal therapy consisting of
      extensive resections including peritonectomy and open hyperthermic
      intraperitoneal chemotherapy appears to be a promising approach. These time
      consuming procedures can be performed with an acceptable morbidity and mortality
      and may improve the poor prognosis of these patients. Further studies are
      necessary to answer such questions as patient selection and optimal mode of
      cytostatic application.

PMID- 9931905
TI  - [Optimized laser-induced thermotherapy in treatment of liver metastases of
      colorectal carcinomas, an interdisciplinary responsibility--a clinical study].
AB  - In a clinical study, it was investigated whether local tumor control is
      attainable with laser-induced thermotherapy (LITT) in the treatment of colorectal
      liver metastasis tumors. Local control of tumor growth was obtainable in
      completely hyperthermic tumors. Due to the small and inhomogeneous patient
      population (n = 32), an assessment of the method regarding prognostic gain for
      the patient is not possible in such a short follow-up period.

PMID- 9931907
TI  - [Thermal laser dosimetry in treatment of liver tumors--correlation of optical
      tissue parameters with in vivo temperature distribution in VX-2 tumors and
      healthy liver tissue].
AB  - Optical properties and in-vivo temperature distribution during laser-induced
      thermotherapy in normal and tumorous rabbit liver were correlated. Lower
      absorption and scattering led to a higher optical and thermal penetration depth
      in the tumor tissue.

PMID- 9931906
TI  - [Multicenter phase II study of the Liver Metastases Study Group of weekly intra
      arterial 24-hour high dose therapy with 5-FU and folinic acid (FA) in liver
      metastases of colorectal tumors].
AB  - This prospective multicenter trial was performed to determine the response rate,
      toxicity and applicability of continuous 24 h hepatic arterial infusion of high
      dose 5-FU and folinic acid. An improved response rate (60.5% in non-pretreated
      patients) was however associated with many systemic side-effects (340/509),
      mainly nausea and diarrhea. Therefore this treatment should be applied only in
      selected patients in specialized centers.

PMID- 9931908
TI  - [Differences in properties of interstitial procedures and their effect on
      clinical applications].
AB  - The effects of percutaneous ethanol injection (PEI) and cryosurgery (CS) on
      normal liver tissue are investigated in a mini-pig model. It was not possible to
      create a circumscribed, reproducible necrosis by PEI; there was a high incidence
      of thromboembolic complications. Due to the discrepancy between the temperatures
      necessary to induce freezing and to induce total cell destruction, the necroses
      were smaller than the ice balls induced by CS and contained vital cells in their
      periphery. In conclusion, PEI should not be used when ethanol spreading into
      normal parenchyma has to be assumed, and the difference in size between ice ball
      and complete necrosis has to be considered in tumor treatment by CS.

PMID- 9931909
TI  - [Locoregional recurrence of melanomas of the extremities after hyperthermic
      extremity perfusion: is reperfusion of value?].
AB  - Isolated limb reperfusion in patients with locoregional recurrence after previous
      isolated limb perfusion achieves local tumor control in a high percentage of
      cases. One of the main aims of the repeat procedure is limb salvage, which was
      possible in 96% of our patients. Complication rate of reperfusion is acceptably
      low.

PMID- 9931910
TI  - [Diameter of metastases is decisive for local treatment outcome of cryotherapy of
      colorectal liver metastases].
AB  - In a retrospective analysis we aimed to assess the incidence of local recurrence
      at the cryosite as well as possible prognostic indicators for the disease-free
      interval at the cryosite following hepatic cryotherapy for non-resectable
      colorectal metastases. At a median follow-up of 22 months, 66 of 85 patients had
      developed tumor recurrence, involving local recurrence at the cryosite in 28
      patients, with cryoablated metastases of > 3 cm being associated with shorter
      disease-free intervals at the cryosite. Improvements in probe placement and
      monitoring of the freezing process are required to allow successful treatment of
      large liver metastases.

PMID- 9931911
TI  - [Intra-arterial (5-FU/FA and FUDR) versus systemic chemotherapy (5-FU/FA) of non
      resectable colorectal liver metastases].
AB  - The relative efficacy of HAI FUDR, HAI 5-FU/FA, and i.v. 5-FU/FA chemotherapy for
      the treatment of unresectable colorectal liver metastases was compared in a
      prospective randomized clinical trial. The response rate after HAI treatment was
      significantly higher as compared to i.v. treatment with no statistical benefit
      regarding survival and time to progression. HAI FUDR treatment was inferior as
      compared to HAI or i.v. 5-FU/FA. i.v. 5-FU/FA-therapy is therefore the method of
      choice outside clinical trials.

PMID- 9931912
TI  - [Protein expression of hMSH2 and hMLH1 in HNPCC: evaluation of a prescreening
      method].
AB  - We show that immunohistochemistry for hMSH2 and hMLH1 is an easy and reproducible
      routine procedure. The interpretation of the staining results is unequivocal and
      investigator-independent. It is now necessary to validate the specificity and
      sensitivity of the method in a multicenter study with tumors of known mutations.
      As a consequence perhaps MIN testing may be replaced by immunohistochemistry as a
      first-line pretesting for HNPCC, reducing cost and time required.

PMID- 9931913
TI  - [Mutation localization as a guide for surgical approach in familial adenomatous
      polyposis?].
AB  - Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is considered
      the operative therapy of choice for the prophylactic treatment of FAP. Recently,
      Vasen and coworkers [5] after correlating the incidence of metachronous rectal
      cancer with the site of the causative APC mutation suggested subtotal colectomy
      and IRA to be the primary treatment in patients with mutations proximal to codon
      1250, whereas IPAA should be performed in those with mutations beyond this codon.
      Mutation analysis in our patients after IRA, however, shows the majority of APC
      mutations to be located proximal to codon 1250 even in those patients with severe
      rectal polyposis and metachronous rectal cancer, thus not supporting the
      therapeutic recommendations of Vasen and coworkers.

PMID- 9931914
TI  - [Rectal carcinomas in HNPCC].
AB  - The true incidence of rectal cancer in HNPCC is still unknown. In our
      retrospective series analyzing 42 probands from HNPCC families, we found rectal
      cancer primaries in 29% of our probands. Patients with a first cancer diagnosed
      in the rectum developed metachronous colon cancer in 54% of the cases. These
      numbers indicate a requirement to discuss the most appropriate surgical procedure
      for preventive intervention (ileorectal anastomosis versus ileoanal pouch
      procedure).

PMID- 9931915
TI  - [Cytokine regulated expression of Fas-Ligand by colon carcinoma cells].
AB  - We studied the proliferative response of tumor-infiltrating lymphocytes (TIL)
      from colorectal carcinomas to rIL-2 as well as their cytotoxic activity which was
      reduced as compared to autologous peripheral blood lymphocytes. We observed TIL
      to be polyclonal and asked if Fas-ligand-expressing tumor cells are responsible
      for the elimination of specific T-cells. Therefore we studied the expression of
      Fas-ligand by LS174T colon carcinoma cells which we showed to be induced by
      cytokines.

PMID- 9931916
TI  - [Ribozyme targeting as gene therapy method for treatment of malignant tumors].
AB  - Using HER-2- and pleiotrophin-targeting ribozymes we demonstrated that ribozymes
      can be used to identify molecules which are highly relevant for tumor growth.
      Furthermore, ribozymes may be a useful new tool for a highly specific and
      efficient adjuvant therapy.

PMID- 9931917
TI  - [Volumetry of circumscribed liver changes with 3-D ultrasound in comparison with
      3-D computerized tomography].
AB  - The accuracy of volume measurement using three-dimensional ultrasound (3D-US) in
      comparison to three-dimensional computer tomography (3D-CT) was evaluated in 11
      patients. The deviation of tumor volumes measured with 3D-US (ellipsoid formula)
      from 3D-CT was -28% to +9% and for 3D-US (planimetry reconstruction) from 3D-CT
      was -21% to +9%. These data show that volume measurement using 3D-US provides
      comparable results to 3D-CT. Clinically, 3D-US could be helpful in the follow-up
      of patients with non-resectable tumors or in planning liver resections by
      assessing the volume of liver tissue remaining after resection or by a better
      visualization of the topography of liver tumors and major hepatic structures.

PMID- 9931919
TI  - [Can the extent of pancreatic tumors be evaluated reliably enough by positron
      emission tomography (PET)].
AB  - We made PET scans using 18 FDG for 46 patients admitted for pancreatic surgery.
      The method yielded a sensitivity of 86% and a specificity of 67%. PET does not
      allow precise exclusion of malignant tumors and therefore invasive diagnostic
      procedures may not be reduced.

PMID- 9931918
TI  - [Perspectives of virtual control of visceral surgery interventions in open MRI].
AB  - Since July 1997 we have operated on 23 patients with different visceral surgical
      diagnoses in an open-configured Magnetic Resonance System (MRI). Among them we
      found 7 patients with benign soft tissue tumors, 5 patients with anal fistulas, 1
      patient with an abscess on the pelvic wall, 1 patient with a rectocele, 1 patient
      with an inoperable, restrictive oesophageal carcinoma, and 8 patients with
      metastatic lesions in the liver. In the last 8 patients we performed MRI-guided
      laser-induced interstitial thermotherapy, in one patient in an open development.
      We did not face any postoperative complications. The median duration of the
      intervention was 2 hours, pre- and postscans included. Our experiences show that
      it is possible to carry out visceral surgical interventions in the open
      configured MRI. The main indications we see now are anal fistulas, soft tissue
      tumors and MRI-guided laser-induced interstitial thermotherapy of liver
      metastases.

PMID- 9931920
TI  - [Effect of MR mammography on surgical procedure in operative treatment of breast
      cancer].
AB  - In addition to conventional imaging techniques, magnetic resonance (MR)
      mammography is an important tool in the diagnosis of breast cancer. It has proved
      to be the method of choice especially for the differential diagnosis of
      discrepant findings between mammography and ultrasound as well as the detection
      of multifocal and multicentric disease. In this context MR mammography is a
      meaningful method for the planning of breast preserving surgery and seems likely
      to become routine practice as long as the preconditions for high quality
      performance are guaranteed.

PMID- 9931921
TI  - [Can noninvasive gadolinium 3D MR subtraction angiography of visceral arteries
      replace conventional intra-arterial catheter angiography?].
AB  - Classic catheter angiography is compared with 3D gadolinium MR angiography for
      evaluation of the vascular anatomy of the celiac trunk, liver supplying arteries,
      and the portal venous system. Based on 10 patients, this study shows the value of
      this new non-invasive method of angiography for the diagnosis of visceral
      vascular anatomy. For this diagnosis MR angiography is expected to replace
      conventional angiography in the near future.

PMID- 9931922
TI  - [Strategy and outcome of interdisciplinary therapy of ovarian carcinomas].
AB  - In this retrospective trial we analyzed the data for 200 patients with serous
      papillary ovarian cancer. The patients were treated with various operation
      strategies following an interdisciplinary conference among a surgeon, a
      gynecologist, and an oncologist. Mean overall survival was 26 months. It was
      significantly better in patients with primary and secondary debulking operations
      in combination with sufficient postoperative chemotherapy. The morbidity rate
      reached 16.8%, the overal mortality rate was 5.7%. The mortality for the first
      surgical intervention was 0%.

PMID- 9931923
TI  - [Urologic reconstruction within the scope of interdisciplinary pelvic
      exenteration for treatment of invasive tumors of the pelvis].
AB  - In radical surgical treatment of primary or recurrent locally advanced pelvic
      carcinoma involving the bladder, urinary diversion after cystectomy significantly
      increases the overall morbidity rate. Analyzing 20 patients retrospectively who
      underwent total pelvic exenteration from 1988-1997, we found that reconstruction
      by ileal conduit can be performed safely but leaves the patient with a (mostly
      second) stoma. The advantage of continence with pouch or neobladder
      reconstruction needs to be weighed up in view of the more demanding and
      complicating surgical technique, hence it should be reserved for younger,
      cooperative patients presenting with a favorable long term prognosis.

PMID- 9931925
TI  - [Interdisciplinary multi-modality therapy of advanced hypopharyngeal and proximal
      esophageal carcinomas].
AB  - A multimodal interdisciplinary concept including an aggressive neoadjuvant
      radiochemotherapy and a multivisceral resection with esophagolaryngectomy and
      bilateral modified neck dissection was introduced for the treatment of tumors of
      the cervical esophagus and hypopharynx. In 75% of the patients a R0-resection was
      achieved resulting in a 5-year survival rate of 38.5% and good functional
      results. Free jejunal interposition was the most favorable reconstruction because
      gastric transposition was followed by an increased rate of anastomotic
      insufficiencies and stenoses requiring bouginage.

PMID- 9931924
TI  - [Invasive carcinomas of the hypopharynx with esophageal involvement-
      multidisciplinary treatment concept].
AB  - In UICC stage IV hypopharnygeal cancer, a radical approach with circular laryngo
      pharyngo-esophagectomy with ipsilateral radical neck dissection and contralateral
      modified radical neck dissection, reconstruction of the pharynx defect with a
      fundus-rotation-gastroplasty, and postoperative high-dose cervical radiotherapy
      improves long term survival and maintains a good quality of life.

PMID- 9931926
TI  - [Resection and replacement of the cervical esophagus and hypopharynx--an
      interdisciplinary responsibility for visceral, micro- and ENT surgeons].
AB  - From 1984 to 1996, 136 carcinomas of the esophagus and 8 of the hypopharynx were
      resected using 3 different procedures (94 transmediastinal, 36 transthoracic, 14
      cervicoabdominal). The hospital mortality rate for cervicoabdominal resection
      (0%) is unequivocally lower than that of the transmediastinal (17.1%) or
      transthoracic (14.3%) methods. The 5-year survival rates are not significantly
      different (24%, 22%, 17%).

PMID- 9931927
TI  - [Minimal invasive surgical treatment of coronary multi-vessel disease].
AB  - To reduce surgical trauma and median sternotomy related complications in cardiac
      surgery, a new minimally invasive surgical technique has been developed for the
      treatment of coronary artery multivessel disease using a small left lateral chest
      incision in the 3rd intercostal space. This technique enables direct LIMA
      harvesting and performance of bypass surgery upon all coronary vessels with
      cardiopulmonary bypass and cardioplegic arrest. So far, 123 patients have been
      treated with this procedure and survived with fewer complications, and we believe
      that routine application of this procedure will lead to reduced morbidity in
      patients receiving coronary artery bypass surgery, short hospital stay and early
      convalescence, combined with good cosmetic results.

PMID- 9931928
TI  - [Minimally invasive thoracic surgery--evaluation after 5 years].
AB  - A prospective study documented all minimally invasive operations performed in the
      department of thoracic surgery between 1992 and 1996. The most frequent
      indications were: lung biopsy (n = 181, 30.9%), coin lesions of unknown origin (n
      = 179; 30.5%), pneumothoraces (n = 133; 22.7%), pleura effusions (n = 19; 3.2%),
      and pleura empyema (n = 13; 2.2%). The majority (82.6%) of the minimally invasive
      procedures were completed without conversion; in 6.0% an extension (< 5 cm) of
      one of the trocar incisions was necessary and in 11.5% an anterolateral
      thoracotomy. It is demonstrated that a wide spectrum of thoracic operations can
      be performed by the minimally invasive approach.

PMID- 9931929
TI  - [Significance of the heart-lung machine for the concept of minimal invasive heart
      surgery].
AB  - Proinflammatory cytokines have been implicated in mediating myocardial
      dysfunction in a systemic inflammatory reaction following open heart surgery with
      extracorporeal circulation (ECC). The present study aimed to distinguish the
      surgical impact on cytokine release from the influence of ECC in a model of
      supported angioplasty. The extracorporeal circulation and not surgical trauma was
      found to be the main trigger of the systemic inflammatory response.

PMID- 9931930
TI  - [Laparoscopic anti-reflux surgery in gastroesophageal reflux. Diagnosis, surgical
      technique and outcome in 143 patients].
AB  - Within the period March 1994 to March 1998, 143 patients with gastroesophageal
      reflux disease (GERD) underwent laparoscopic antireflux surgery. According to
      manometric studies, 76 patients underwent short-floppy laparoscopic Nissen
      fundoplication, 42 patients with impaired motility had a Toupet
      hemifundoplication, and 25 patients had an anterior Dor hemifundoplication.
      Recurrent reflux symptoms appeared in 6.3% after 16.7 +/- 12 months of follow-up
      (Nissen 2.6%, Toupet 2.3%, Dor 24%, p < 0.01). Persistent dysphagia with
      reoperation occurred in 2.1% (Nissen 2.6%, Toupet 2.3%, Dor = 0%, n.s.). Follow
      up included assessment of the Visick score and patient satisfaction with
      operation results. Excellent or good results were found in 92% of the patients.

PMID- 9931932
TI  - [Results of laparoscopic fundoplication for treatment of gastroesophageal
      reflux].
AB  - We report on 48 patients, treated by laparoscopic fundoplication for pronounced
      gastroesophageal reflux disease. The results show that laparoscopic
      fundoplication is a very safe, gentle, and successful procedure for the therapy
      of gastroesophageal reflux disease. We regard laparoscopic fundoplication as a
      good alternative to long term medical therapy if a careful diagnosis and
      indication is provided.

PMID- 9931931
TI  - [Rediscovered techniques--Janeway laparoscopic gastrostomy in comparison with
      Witzel fistula].
AB  - We present the results of 20 patients with a laparoscopic gastrostomy according
      to Janeway. The laparoscopic gastrostomy was associated with less operation time,
      less analgetic consumption, and less discomfort in comparison to 24 patients with
      a Witzel fistula.

PMID- 9931933
TI  - [Laparoscopic colorectal resection--a routine procedure?].
AB  - Out of 234 elective patients 162 (69%) with colorectal disease were resected by
      laparoscope. The conversion rate was 8.5%. Mortality and morbidity were low.
      Patients' recovery was quick. A total of 96 patients were operated because of
      colorectal cancer. The number of resected lymph nodes and resection margins was
      sufficient. No port metastases were observed. Six patients developed either
      perineal or hepatic tumor recurrence.

PMID- 9931934
TI  - [Laparoscopic colorectal resections: indications, surgical technique and outcome
      in 410 prospective cases].
AB  - From April 1993 to August 1997 410 patients underwent laparoscopic surgery for
      colon and rectal diseases. In the beginning we only operated on patients with
      benign disorders. Since July 1995 colorectal malignancies have also been
      resected. A total of 181 patients (47.6%) with benign colorectal diseases were
      operated on; 116 patients (31%) had diverticulosis, diverticulitis or benign
      tumor; 26 with rectal prolapse were resected in MIS-technique. In all, 199
      patients were treated for colorectal malignancies, 171 (85.9%) with curative
      intention. RESULTS: Mean operation time was between 60 and 520 min. After 40
      operations the learning curve had reduced the operation time significantly.
      Severe complications appeared in 4.7% of all cases.

PMID- 9931935
TI  - [Initial applications of a new trochar system for non-laparoscopic intraluminal
      surgery].
AB  - Instruments that have been used in flexible endoscopy have always been confined
      to the working channel of the endoscope. We have therefore developed a device
      that allows transabdominal manipulation in the stomach under gastroscopic control
      with a device similar to a percutaneous endoscopic gastrostomy (PEG). For the
      first clinical application of this device it was used in order to perform
      pseudocystogastrostomy in patients with pancreatic pseudocysts.

PMID- 9931936
TI  - [Endoscopically-assisted lipoma removal].
AB  - Since 1994 we have been removing large capsulated lipomas which are localised in
      an esthetically exposed and/or functional region using endoscopically assisted
      technique. This technique is minimally invasive and allows optimal visualisation
      of the tumour during the removal. Only a small incision is required to prepare
      the tumour in toto with capsula. With the endoscopic control of the wound we can
      avoid greater haematomas, which is very important for wound healing.

PMID- 9931937
TI  - [Surgical interventional endoscopic treatment concept of bile duct lesions after
      laparoscopic cholecystectomy].
AB  - In this study we analysed 25 patients with bile duct injuries following
      laparoscopic cholecystectomy retrospectively. Reconstructive surgery was
      necessary in 24 patients with bile duct lesions that could not be treated
      endoscopically. After a mean follow-up of 28 months (3-65) we have good
      functional outcome in the majority of patients, however, one patient required
      liver transplantation because of secondary biliary cirrhosis.

PMID- 9931938
TI  - [Therapy and follow-up of injuries after laparoscopic operations].
AB  - From May 1993 to September 1997 we treated 22 patients with complications after
      laparoscopic surgery. We report on 18 patients after laparoscopic
      cholecystectomy, three patients after diagnostic laparoscopy and one after TAPP.
      Two patients died (hepatic failure and without any possibility of definitive
      therapy) and the injuries of the other 20 patients were repaired.

PMID- 9931939
TI  - [Laparoscopic ultrasound as the standard for intraoperative bile duct evaluation
      within the scope of laparoscopic cholecystectomy].

PMID- 9931940
TI  - [New aspects of laparoscopic cholangiography].
AB  - Cholangiography does not prevent bile duct injury, but if performed properly, it
      can identify impending injury before hand. We present a modified form of
      laparoscopic cholecystcholangiography; only 5 min are required to perform this
      technique. Some 408 consecutive peroperative cholangiographies are analyzed. We
      recommend this method, which decreases the risk of bile duct injuries, reveals
      occult bile duct stones in 4.2%, and gives the opportunity to approximate the
      gold standard of cholecystectomies.

PMID- 9931941
TI  - [Intraoperative routine cholangiography in laparoscopic cholecystectomy].
AB  - In the present study of 1000 patients undergoing laparoscopic cholecystectomy we
      report the results of intraoperative routine cholangiography (IOC). IOC was
      feasible in 89.2% of the patients and presented a complete depiction of the
      extrahepatic bile system in 98.1%. Anatomic variations of the bile system which
      subsequently affected the operative management were found in 12.6% by IOC. In
      conclusion we recommend that using IOC anatomic variations of the bile system can
      be visualised and therefore accidental injuries avoided.

PMID- 9931942
TI  - [Chronic liver immunologic factors in ischemic type biliary lesions (ITBL) -->
      reduced Th1 and increased Th2 response].
AB  - Compared to patients with a stable liver function, we found a decreased Th1 and
      increased Th2 response in patients presenting with ischemic type biliary lesions
      following liver transplantation. It remains open to speculation whether these
      immunological changes were induced by the damage of the bile ducts, occur as an
      additional damaging factor or are found as an epiphenomenon in patients with
      liver transplant dysfunction.

PMID- 9931944
TI  - [Plasma separation and bilirubin adsorption therapy in excessive
      hyperbilirubinemia after liver transplantation].
AB  - Reduction of bilirubin levels by various means has been proposed as symptomatic
      therapy for excessive jaundice in various end-stage liver diseases, since it
      exerts multiple toxic effects and may thereby promote multiple organ failure.
      Plasma separation and bilirubin adsorption by an anion-exchange column (BR-350)
      performed in four patients with excessive hyperbilirubinemia after liver
      transplantation resulted in a 29%-70% reduction in total serum bilirubin,
      accompanied by significant improvement of multiple organ failure or
      encephalopathy in three patients. Bilirubin adsorption may be beneficial in
      complicated jaundice after hepatic transplantation and should further be
      evaluated for its clinical indications.

PMID- 9931943
TI  - [Etiologic factors and incidence of ischemic type biliary lesions (ITBL) after
      liver transplantation].
AB  - Ischemic type biliary lesions (ITBL) are defined as non-ischemic and non
      immunological destruction of the graft's biliary tree after liver
      transplantation. In a retrospective analysis we investigated possible etiological
      factors and the incidence of ITBL. Differing from previous studies, the incidence
      of ITBL was low (2.6%) and we did not observe a significant effect of cold
      ischemic time or initial peak transaminases, as indicator of the reperfusion
      injury. However, we detected a significant decrease in the incidence of ITBL in
      self-retrieved organs and in organs preserved with arterial pressure perfusion.

PMID- 9931945
TI  - [Flow cytometry controlled induction therapy with ATG and noninvasive monitoring
      of rejection--a modern management concept after heart transplantation].
AB  - We introduce our concept of non-invasive transplant monitoring. The introduction
      of individualized immunosuppression by means of flow cytometry leads to a lower
      incidence of acute graft rejection and preserves immuncompetence. With the
      simultaneous use of echocardiography and intramyocardial electrogram (IMEG) acute
      graft rejections can be safely identified without using any invasive method.

PMID- 9931946
TI  - [33 years kidney transplantation in Zurich].
AB  - This article summarizes our experience with renal transplantation over the past
      33 years and shows progressive improvement of the clinical outcome over time. In
      parallel we observed an increasing proportion of elderly recipients and
      diabetics. The increasing shortage of cadaver grafts was compensated by using
      donor hearts from legally dead donors (heart no longer beating) and establishing
      a living donor program.

PMID- 9931947
TI  - [Kidney retransplantation in relation to organ shortage].
AB  - This article reviews our experience with renal regrafting in the past 16 years
      with particular emphasis on long-term outcome and prognostic parameters. Among
      1094 renal transplants there were 15.8% regrafts, and the proportion of patients
      awaiting a regraft procedure on our current waiting list is 33%. Graft and
      patient survival was similar for first and second transplants, but was
      significantly reduced when a third graft was performed. The main prognostic
      parameters were the time of function of the previous graft, mismatch for HLA-DR
      and the presence of panel-reactive antibodies.

PMID- 9931948
TI  - [Primary vesico-renal reflux in children and adults. History].

PMID- 9931949
TI  - [Primary vesico-renal reflux in children and adults. Definitions].

PMID- 9931950
TI  - [Primary vesico-renal reflux in children and adults. Epidemiology].

PMID- 9931951
TI  - [Primary vesico-renal reflux in children and adults. Anatomo-physiologic aspects
      of reflux].

PMID- 9931952
TI  - [The physiopathology of vesico-renal reflux].

PMID- 9931953
TI  - [The nephropathies of reflux].

PMID- 9931954
TI  - [Primary vesico-renal reflux in children and adults. Clinical diagnosis].

PMID- 9931955
TI  - [Primary vesico-renal reflux in children and adults. Diagnostic imaging and
      classification].

PMID- 9931956
TI  - [Biologic diagnosis of reflux nephropathies].

PMID- 9931957
TI  - [Is there still a place for endoscopy in the diagnosis and therapeutic management
      of vesico-renal reflux?].

PMID- 9931958
TI  - [The natural history of primary vesico-renal reflux. The probability of
      spontaneous remission].

PMID- 9931959
TI  - [Prospective studies on vesico-renal reflux].

PMID- 9931960
TI  - [Medical treatment of vesico-renal reflux].

PMID- 9931961
TI  - [Primary vesico-renal reflux in children and adults. Conventional surgical
      treatment].

PMID- 9931963
TI  - [Primary vesico-renal reflux in children and adults. Contralateral reflux after
      treatment of unilateral reflux].

PMID- 9931962
TI  - [Endoscopic treatment of vesico-renal reflux].

PMID- 9931964
TI  - [Vesico-renal reflux and duplication of the urinary tract].

PMID- 9931965
TI  - [Reflux from a solitary kidney. Reflux and multicystic renal dysplasia or
      unilateral renal agenesis].

PMID- 9931966
TI  - [Vesico-renal reflux and anomalies of the pyelo-ureteral junction].

PMID- 9931967
TI  - [Should circumcision be performed in young boys with vesico-ureteral reflux?].

PMID- 9931969
TI  - [Familial vesico-renal reflux (genetic aspects of primary reflux)].

PMID- 9931970
TI  - [Primary vesico-renal reflux in children and adults. Therapeutic strategies].

PMID- 9931968
TI  - [Fetal reflux--neonatal reflux].

PMID- 9931971
TI  - [Primary reflux in adults].

PMID- 9931972
TI  - [Technical bases and acquisition conditions of electron-beam computed
      tomography].
AB  - PURPOSE: In this review the technical principle and scanner characteristics of
      electron beam computer tomography (EBCT) are discussed. METHODS: In contrast to
      conventional CT, image acquisition in EBCT is achieved without mechanically
      moving parts. This construction allows for short acquisition times in
      investigating given anatomical regions (100 ms per slice) or up to 8 levels
      without table movement and short interscan delays (50 ms per slice). RESULTS:
      Depending on the nature of the investigation, the scanner can be used in the
      single slice, continuous volume scanning and multi slice mode. The single slice
      mode is used for detection and quantification of coronary calcifications and for
      CT angiography of the coronary vessels. Equivalent to the spiral mode in
      conventional CT, continuous volume scanning may be used for routine investigation
      of the chest and abdomen. Functional investigations of the heart and perfusion
      measurement of different organs can be performed in multi slice mode. Because of
      the geometry of the electron beam scanner, radiation exposure for certain
      investigations is above the exposure with conventional CT. CONCLUSION: Future
      developments will focus on dose efficient radiation collimation, high resolution
      detector systems and artefact reducing reconstruction kernels.

PMID- 9931973
TI  - [Performance of electron-beam CT: continuous-volume-scan compared to spiral CT].
AB  - To compare patient dose and image quality of electron-beam-CT vs. spiral-CT by
      means of phantom measurements. An EBCT scanner (C-150 XP) and a spiral-CT scanner
      (GE HiSpeed Advantage) were used to scan three different phantoms. Administered
      dose, high contrast (HC) resolution, low contrast (LC) lesion detectability and
      the width of the radiation beams were measured. EBCT showed 25-35% lower HC
      resolution in comparison to spiral-CT. LC lesion detectability showed equivalent
      results for S/N vs. patient dose using 3 mm collimation with EBCT and spiral-CT,
      whereas spiral-CT was superior for 1.5 and 6 mm collimation. Dose measurements
      revealed a 2 fold higher patient dose using EBCT with 1.5 mm or 6 mm collimation
      compared to spiral-CT using equivalent scan parameters. No differences were seen
      using 3 mm collimation. Differences were due to insufficient beamside collimation
      of the EBCT. The use of EBCT with 6 mm collimation should be avoided, because of
      impaired performance. Using 3 mm collimation, EBCT showed comparable performance
      like state of the art spiral-CT despite lower HC resolution.

PMID- 9931975
TI  - [Methods of quantification of coronary artery calcifications with electron-beam
      and conventional computed tomography].
AB  - PURPOSE: To compare electron beam CT (EBCT) und prospectively ECG gated
      conventional CT for the detection and quantification of coronary artery
      calcifications. METHODS: 42 patients (mean age 62.8 +/- 8.8 years) were scanned,
      both with EBCT and ECG gated sequential CT. For quantification, the traditional
      "total calcium score" (TCS) according to the Agatson method as well as the
      "volumetric calcium score" (VCS) as determined with a stand-alone workstation
      (NetraMD) was calculated for both modalities. RESULTS: There was close
      correlation between EBCT and conventional CT, both for TCS (r = 0.984) as well as
      for VCS (r = 0.986) score values. The median difference was 17% for TCS and 13%
      for VCS. The difference between the two modalities was not statistically
      significant (p = 0.44). CONCLUSION: EBCT and prospectively ECG triggered
      conventional CT are equivalent for the quantification of coronary artery
      calcifications. The extent of calcifications can be established with both
      modalities using either TCS or VCS score values.

PMID- 9931974
TI  - [Significance of calcium detection with electron-beam tomography in coronary
      disease].
AB  - PURPOSE: Coronary calcium is a powerful indicator of arteriosclerosis and can be
      detected very precisely with electron beam tomography. The method can be applied
      in patients with known coronary artery disease or in asymptomatic patients at
      risk of arteriosclerotic disease. METHODS: The standard protocol of EBT consists
      of 30 to 40 slices of 3-mm thickness with a scan time of 100 ms, no overlap. No
      contrast medium is needed. The total scan can be performed within one breathhold.
      The calcium score is calculated as described by Agatston. Radiation exposure
      amounts to 0.8 mSv per total screen. We used spiral CT with and without ECG
      trigger as an alternative. RESULTS: At the University of Munich we performed an
      EBT scan of the heart in 1100 patients within the last year. In 567 patients
      coronary angiography was performed also (+/- 3 days). Confirming previous reports
      in the literature, we found a correlation of the calcium score with the age and
      gender of the patients. Severe coronary artery disease (stenoses > or = 75%) was
      associated with significantly more calcium than less severe CAD. The calcium
      score did not discriminate between one-, two- and three-vessel disease. The site
      of calcification does not correlate with the localization of stenoses. Thirty
      three percent of the patients with significant coronary artery disease showed a
      normal age-adjusted calcium score; a total of 8.1% of patients with severe
      stenoses did not reveal any coronary calcification (score = 0). With asymptomatic
      patients there are only a few studies available. Soft plaques cannot be detected
      with EBT, but in most patients soft plaques occur together with hard plaques. Our
      results show that spiral CT of the newest generation may also be used for calcium
      screening. There was an excellent correlation of the calcium scores of EBT and
      spiral CT at all levels of calcification. DISCUSSION: Coronary calcium is a
      sensitive marker of coronary artery disease. In the clinical setting EBT is
      indicated in patients with known coronary artery disease (to evaluate prognosis),
      in patients who are unable to perform a stress test, and in patients with
      atypical chest pain. However, lack of calcification may be associated with severe
      stenoses in a minority of patients. The clinical value in asymptomatic patients
      needs to be defined: randomized studies are necessary. We see a possible
      indication in patients with known risk factors, in whom primary preventive
      strategies could be performed more selectively and cost-effectively.

PMID- 9931976
TI  - [Significance of electron-beam tomography in the evaluation of the patency of
      aortocoronary bypasses].
AB  - PURPOSE: Electron beam tomography (EBT) permits acquisition of images with high
      spatial and temporal resolution. The value of EBT and other imaging modalities
      for the depiction of patent coronary artery bypass grafts (ACVB, IMA) are
      compared to coronary angiography and an overview of current results is given.
      MATERIAL AND METHODS: Graft patency can be evaluated with indirect methods
      stress, such as echocardiography, radionuclide ventriculography, myocardial
      scintigraphy, positron-emission tomography (PET) and direct imaging modalities,
      such as Doppler/2D echocardiography, EBT, spiral computed tomography (SCT) and
      magnetic resonance angiography (MRA). RESULTS: With indirect methods graft
      patency can be evaluated with sensitivity of 64-100% and specificity of 73-100%.
      EBT and SCT are equivalent in sensitivity (= 94%) in the assessment of open
      venous grafts and specificity is up to 100%, but EBT is superior in the diagnosis
      of patent IMA grafts (sensitivity 100% vs 89%). Visualization of high-grade
      venous bypass stenosis seems possible with EBT. MRA with gradient echo technique
      is highly accurate in the assessment of patent venous grafts (sensitivity 77-93%)
      but has limited value in the evaluation of IMAs (sensitivity = 53%). Promising
      are ultrafast 3D-MRA methods which permit high accuracy (sensitivity = 94-96%) in
      assessing venous and arterial grafts. DISCUSSION: Indirect imaging methods cannot
      differentiate between an occluded bypass, progression of coronary artery disease
      and myocardial infarction. EBT and SCT are equivalent in the diagnosis of open
      and occluded venous grafts, but EBT is superior in the assessment of patent IMA
      grafts. Visualization of high-grade venous bypass stenosis seems possible with
      EBT. MRA techniques, especially ultrafast 3D-MR methods, are highly accurate in
      the assessment of patent venous and arterial grafts but are still limited to
      scientific research.

PMID- 9931977
TI  - [Functional imaging of the heart with electron-beam computed tomography].
AB  - PURPOSE: Electron-beam computed tomography (EBCT) enables examinations with a
      very short acquisition time of 50 ms and thus permits cardiac imaging without
      motion artifacts. Utilizing eight detector rings simultaneous image acquisition
      in up to eight levels and complete imaging of the whole heart is possible. In
      studies, functional imaging with EBCT was compared to our angiocardiography,
      echocardiography, radionuclide, ventriculography and magnetic resonance
      tomography. MATERIALS AND METHODS: ECG-triggered long- and short-axis cine
      studies were performed with the Imatron C-150 Evolution, acquiring 160 and 156
      images at 8 and 12 levels. After manual tracing of epicardial and endocardial
      borders, ventricular size, ejection fraction, wall-thickening and myocardial mass
      were calculated. RESULTS: A very high correlation between EBCT and direct
      determination of right and left ventricle (r = 0.98 and r = 0.99) was
      demonstrated. Compared to echocardiography, angiocardiography and radionuclide
      ventriculography, assessment of ventricular function was more precise and more
      reliable. DISCUSSION: EBCT allows the exact and reliable determination of left
      and right ventricular function. Also precise assessment of myocardial mass is
      possible. However, the high radiation exposure and diagnostic effort have to be
      considered.

PMID- 9931978
TI  - [Thoracic diagnosis with electron-beam computed tomography].
AB  - The electron beam computed tomography (EBCT) is characterised by an up to 10-fold
      increased speed in comparison to a spiral CT scanner. Although originally
      designed for diagnosing the heart, some indications in the chest and for the
      vessels have also become well established. In the forefront exists the
      possibility to exam a large volume with a small slice thickness in a short time
      period without having to sacrifice on important features of spiral CT scanning.
      During one breathhold, the thorax can be continually examined with 1.5 mm slice
      thickness, which means that indications for high-resolution (HR-) CT, spiral-CT
      and for virtual bronchoscopy can be combined into one examination. Beyond the
      artefact-reduced images, the EBCT presents image data which, following image
      processing (sliding MIPs, coronal reconstructions), allow recognition of a new
      horizon in thoracic diagnostics.

PMID- 9931979
TI  - [Diagnosis of pulmonary embolism with spiral and electron-beam CT].
AB  - PURPOSE: To compare spiral (SCT) and electron-beam CT (EBT) for the diagnosis of
      pulmonary embolism (PE). MATERIALS AND METHODS: From June 1997 to June 1998 188
      patients with suspected acute or chronic thromboembolism of the pulmonary
      arteries were examined. A total of 108 patients were scanned using SCT and 80
      patients using EBT. On each scanner two different scan protocols were evaluated.
      RESULTS: PE was diagnosed in 38 patients using EBT and in 49 patients using SCT.
      Especially with EBT, isolated peripheral emboli could be confidently diagnosed.
      When EBT and SCT were compared for the analysis of peripheral pulmonary arteries,
      some paracardiac segmental and subsegmental vessels were significantly better
      analyzable with EB. Additional or diseases other than PE were diagnosed in 112
      patients. Other diagnoses included bronchial carcinoma and aortic dissection.
      CONCLUSIONS: Advanced CT scanning techniques allow the highly accurate diagnosis
      of central and peripheral PE. Other potentially life-threatening underlying
      diseases are also readily recognized.

PMID- 9931980
TI  - [Electron-beam computed tomography in heart surgery].
AB  - PURPOSE: Electron beam CT (EBCT) has been devised to improve the imaging of the
      heart and the great vessels. Therefore, this method is expected to facilitate the
      imaging workup of patients referred for cardiothoracic surgery. We set out to
      review the most important surgical issues that can be addressed with this method.
      METHODS: From June, 1997 until July, 1998, more than 300 patients were referred
      from cardiothoracic surgery. In a retrospective analysis, diagnostic results were
      reviewed and compared with surgical findings and the clinical course. RESULTS:
      Aortocoronary bypass graft occlusions were detected with a sensitivity of 100%
      and a specificity of 95%. Calcifications of the aorta, pericardium and
      intracardiac tumors were surgically confirmed in all instances. There was a
      significant association of the degree of coronary artery calcification and the
      progression of cardiac allograft vasculopathy in 50 heart transplant recipients.
      In EBCT of the aorta, a high degree of diagnostic confidence was found for aortic
      dissection, aortic wall hematoma or aortic perforation. CONCLUSIONS: We conclude
      that EBCT represents an important diagnostic tool both for surgical planning and
      postoperative surveillance in cardiothoracic surgery.

PMID- 9931981
TI  - [Calculation of absolute cerebral blood volume and cerebral blood flow by means
      of electron-beam computed tomography (EBT) in acute ischemia].
AB  - The utility of electron beam computed tomography (EBT) to estimate cerebral blood
      volume (CBV) and cerebral blood flow (CBF) was evaluated. Eleven patients with
      suspected acute cerebral ischemia were investigated. The EBT was performed with
      an acquisition time of 50 ms per slice at eight parallel levels. To compare
      signal/noise and contrast/noise ratios the data from the EBT investigation were
      compared to a similar examination on a spiral CT. The signal/noise ratio with EBT
      was about 30%, the contrast/noise ratio 25% of that with spiral CT. The absolute
      values of CBV were 4.9 +/- 1.2 ml/100 g (EBT); CBF was 50.5 +/- 7.0 ml/100 g/min
      in normal contralateral brain tissue. In four patients with proven infarcts on
      follow-up, the ischemic areas had a CBV ranging from 1.7 to 3.8 ml/100 g, while
      CBF ranged from 9.4 to 24.5 ml/100 g/min. Using a bolus injection of contrast
      material, calculation of absolute CBV and CBF is feasible using EBT. Advantages
      of EBT are the absolute measurements possible and it's multislice capability.
      Disadvantages, however, are caused by the high image noise, limiting the
      demarcation of ischemic tissue.

PMID- 9931982
TI  - [Electron-beam CT-angiography in abdominal aortic aneurysms. Initial results].
AB  - PURPOSE: To evaluate the suitability of ultrafast electron-beam tomography (EBT)
      for the investigation of abdominal aortic aneurysms using CTA. METHODS: Thirty
      one patients with suspected abdominal aortic aneurysm were investigated with EBT
      using an Evolution XP scanner (Siemens, Erlangen) with the newest software
      version 12.34 with continuous volume scanning of 140 images in 17 s. Collimation
      was 3 mm, table increment 4 mm with overlapping image reconstruction every 2 mm,
      exposure time 200 ms (124 mAs), resulting in a scan-range of 28 cm. A quantity of
      80 ml contrast material was administered (flow 4 ml/s). Visualization of the
      abdominal aorta and its branches was performed with MIPs and shaded surface
      display. Evaluation of image quality was based on a four-step classification
      scale (1 = good, 4 = insufficient) for the demonstration of the abdominal aorta
      and the visceral, renal and iliac arteries. RESULTS: All EBT examinations
      demonstrated high and homogeneous density values along the whole vessel course
      with a mean density value of 258.7 +/- 47.3 HU for the abdominal aorta and the
      iliac arteries. Quality evaluation for the vessel demonstration showed mean
      values between 1.22 and 1.57 for the abdominal aorta and the visceral, renal and
      iliac arteries. CONCLUSIONS: EBT with 140 slices and slice reconstruction every 2
      mm offers a high z-axis resolution resulting in high-quality CT angiographies of
      the whole abdominal aorta and its branches.

PMID- 9931984
TI  - [Significance of CT in the detection of regional lymph node metastases in
      colorectal carcinoma].
AB  - PURPOSE: For preoperative staging of colorectal cancer a CT scan is frequently
      performed. This report examines the sensitivity of CT for regional lymph node
      metastasis of colorectal cancer using different criteria. MATERIALS AND METHODS:
      Preoperative CT scans of 153 patients with colorectal cancer were analyzed using
      different criteria for N1. The results were then compared to the postoperative
      histological findings. RESULTS: For N1 = lymph nodes (LN) > 1 cm the sensitivity
      was 47%. For N1 = LN > 1 cm or an increased number of LN < 1 cm the sensitivity
      was 71%. In patients with a primary tumor seen on CT, sensitivity rose to 87%.
      DISCUSSION: Evidence of regional nodal metastatic disease is only relevant for
      rectal cancer, colon polyps, and for locally excised tumors when considering
      present surgical concepts for the treatment of colorectal cancer. In these cases
      CT analysis using the broadened criteria for N1 proposes a valuable argument
      regarding possible preoperative radiotherapy or an operative revision.

PMID- 9931983
TI  - [Diagnosis of the abdominal vascular system by means of electron-beam computed
      tomography (EBT)].
AB  - PURPOSE: To evaluate the potential of electron-beam computed tomography (EBT) in
      the pre- and postinterventional assessment of vascular abdominal pathologies.
      MATERIAL AND METHODS: Forty patients with implanted transjugular portosystemic
      shunt (TIPS), 12 patients with peripheral arterial occlusive disease and 8
      patients with infrarenal abdominal aortic aneurysm after endovascular
      implantation of bifurcation stents were prospectively examined with contrast
      enhanced EBT during one year. The evaluation included analysis of time-density
      curves (TDC) and 3D reconstructions. Results were compared with Doppler
      sonography and/or DSA. RESULTS: In 30 of 40 TIPS patients, identical results were
      found with EBT, Doppler sonography and/or DSA. Reduced perfusions of the TIPS,
      which were subsequently confirmed by DSA, could not be shown with EBT in 3
      patients. Nine of 12 patients with peripheral arterial occlusive disease and
      angiographically proven stenosis (> 75%) showed a reduced and delayed peak
      density of the time-density curves. The quantification of arterial stenosis,
      however, did not follow the angiographic values. In all patients with the
      implanted bifurcation stents, EBT could correctly exclude a leakage of the stent.
      CONCLUSION: EBT has certain advantages over conventional spiral CT in the
      evaluation of abdominal vascular pathologies due to the additional assessment of
      perfusion parameters. Clinical indications for the use of EBT are seen especially
      in the postinterventional follow-up of patients with implanted stents.

PMID- 9931985
TI  - [Chance ultrasonographic findings in a former chemical industry employee].

PMID- 9931986
TI  - [Comments on the work of A. Wackenheim and G. Zollner. Time and Picture.
      Radiologe (1998) 38:321-325].

PMID- 9931987
TI  - [Imaging in intensive medicine. Techniques. Indications, diagnostic signs. II].

PMID- 9931988
TI  - [Reflections on anesthetic risk].
AB  - All anaesthetic drugs and techniques inhere risks, that can cause illness and
      death even in the sound. Beside this common anaesthetic risk caused by
      anaesthesia itself, risks specific for the patient and the surgery, the influence
      of the anaesthetist and the available facilities are additional factors
      contributing to the risk involved for any particular animal. In this article the
      factors in anaesthetic risk and their importance for the individual risk of a
      patient are discussed. Distinct is that a systemic disease and the resulting
      incapacity stand for a much higher risk than anaesthesia by itself or the
      surgery. Beside the preoperative physical status the urgency of the operation has
      a decisive influence upon the anaesthetic risk. Deficient monitoring and an
      unrecognized and/or untreated respiratory depression are the most common reasons
      for anaesthetic death in veterinary medicine. The anaesthetist has a profound
      bearing on the degree of risk to which a patient is exposed, because most of the
      avoidable anaesthetic mishaps are caused by human mistakes. The individual
      anaesthetic risk of a patient is determined with the help of the preanaesthetic
      examination. Referring to the factors in anaesthetic risk strategies for the
      prevention of anaesthetic mishaps and complications are discussed.

PMID- 9931989
TI  - [Case report. Ataxia, consciousness disturbances in a young dog].

PMID- 9931991
TI  - [Periocular additional growth in an elapid (Elaphe quatuorlineata)].

PMID- 9931990
TI  - [New pharmacologic aspects in the neurologic profile of propentofylline (Karsivan
      ad us. vet.)].
AB  - Propentofylline (Karsivan, Hoechst Roussel Vet) is a selective inhibitor of
      adenosine transport and phosphodiesterase. For several years it has been well
      established in the geriatric therapy of the dog improving hemodynamics in
      cerebral and peripheral compartments. In human medicine clinical development of
      this pharmaceutical has already entered an advanced stage for the long-term
      therapy of patients with Alzheimer's disease and vascular dementia. In the brains
      of senile dogs and in human patients suffering from Alzheimer's disease
      comparable neuropathological findings can be made. In senile dogs a distinctive
      correlation exists between the quantity of beta-amyloid accumulation and the
      degree of dementia. The extension of knowledge by clinical studies in humans and
      by experimental studies in animals may contribute to a deeper understanding of
      therapeutical approaches of cognitive dysfunction in the old dog. The xanthine
      derivative propentofylline [1-(5'-oxohexyl)-3-methyl-7-propylxanthine] directly
      interfers with the neurodegenerative process and reduces the extent of damage to
      brain structures. In experimental models of vascular dementia and/or Alzheimer's
      disease it improves cognitive functions, inhibits inflammatory processes as well
      as excessive activation of microglia, formation of free radicals, cytocines and
      abnormal amyloid precursor proteins (APP). It stimulates synthesis and liberation
      of nerve growth factor (NGF) and reduces ischemic damage to the brain. In
      clinical studies in humans it improved cognitive functions as well as global
      functions and the ability to cope with tasks of routine daily life in patients
      suffering from Alzheimer's disease and vascular dementia.

PMID- 9931992
TI  - [CT myelography for diagnosis of brachial plexus avulsion in small animals].
AB  - Avulsion of nerve roots of the brachial plexus can be diagnosed clinically,
      neurologically, radiographically and by electromyography. But like the
      myelography these techniques are inprecise for determination of the severity
      (partial or complete disruption) and the localization of the lesion. In human
      medicine the combination of computerized tomography with myelography shows high
      accuracy. Veterinary reports of experience in this field are not yet known. The
      aim of the present study was to demonstrate nerve root avulsions using
      myelography and computerized tomography. Three dogs and one cat with traumatic
      lesions of the brachial plexus were examined. The lesion could be seen in all
      patients. Thus CT-myelography results in an improved prognostic assessment of
      brachial plexus paralysis. Moreover, this technique could become one of the most
      important diagnostic methods for brachial plexus lesions involving nerve root
      reinsertion--neurotizations in veterinary medicine.

PMID- 9931993
TI  - [Sensory innervation of the hip joint capsule in dogs].
AB  - The innervation of the canine hip joint has become increasingly important in the
      treatment of hip dysplasia and hip arthrosis, since investigations proved that
      simple removal of periosteum around attachment of hip joint capsule, called
      denervation results in an instant analgesia and allows the dog to regain joyful
      freedom of movement. A macroscopic-anatomic examination of 16 canine hips
      furnished new findings and knowledge in the field of veterinary medicine on the
      sensitive innervation of the canine hip joint capsule. Accordingly, the
      craniolateral area of hip joint capsule is innervated by rami articulares of N.
      glutaeus cranialis, the caudolateral area by rami articulares of N. ischiadicus
      and the medial area by rami articulares of N. femoralis.

PMID- 9931994
TI  - [Eosinophilic myositis of the extraocular muscles. A case report].
AB  - Extraocular polymyositis is a rare orbital disease in dogs and has to our
      knowledge never been described in other domestic animals. Typically, dogs are
      presented with a bilateral exophthalmos due to inflammatory swelling of the
      extraocular muscles, similar to the endocrine ophthalmopathy (Graves' disease) in
      man. The latter disease, however, has never been documented in animals. In this
      case report, clinical signs, differential diagnoses, diagnostic work-up and
      successful immunosuppressive therapy are described.

PMID- 9931995
TI  - [Eye diseases in dwarf rabbits. 2. Diseases of the cornea, intraocular and
      retrobulbar disorders, and neoplasms].
AB  - In the second part of this review article the diseases affecting the cornea,
      intraocular and retrobulbar disorders, and eye-neoplasia of dwarf rabbits are
      described. These are illustrated by means of selected photographs.

PMID- 9931996
TI  - [Adenovirus infections in psittacines].
AB  - Diagnostic investigations were carried out in a fatal disease of several African
      Grey Parrots (Psittacus erithacus) and Cape Parrots (Poicephalus robustus) in a
      large breeding plant. Electron microscopically examination of liver and
      intestine, the organs with the most prominent pathomorphological changes,
      regularly revealed adenoviruses. Necrotizing hepatitis and catarrhal to
      haemorrhagic enteritis dominated on histopathological examination. Numerous
      basophilic intranuclear inclusion bodies in hepatocytes and enterocytes and their
      ultrastructural characteristics underline the etiological role of the detected
      adenoviruses. Adenoviruses were isolated from livers of three different birds and
      once from the intestine. Serologically the isolates were classified as fowl
      adenovirus serotype 4 (FAV4). Restriction enzyme analysis of two isolates showed
      the identity with the FAV4 reference strain KR5.

PMID- 9931997
TI  - [Evaluation of the test strip Reflotron ALP (alkaline phosphatase) for blood
      samples of dogs and cats].
AB  - The test strip Reflotron ALP (alcaline phosphatase) was evaluated for use in
      canine and feline heparinized blood samples. The within-run and the day-to-day
      precision of blood and plasma samples was excellent. A haematocrit up to 60% of
      canine blood and up to 50% of feline blood had no influence on the measurements.
      Reflotron ALP was compared with ALP on Hitachi 717 (Boehringer Mannheim,
      Mannheim, Germany). The correlation of both methods was good for canine and
      feline blood samples. Reflotron ALP was higher than Hitachi ALP in both species.
      Despite an enormous deviation between Reflotron ALP and the reference method of
      canine and feline blood samples within the reference range, Reflotron ALP is a
      suited test for the detection of elevated ALP activity in canine and feline blood
      samples. Differences of the ALP activity might be caused by ALP isoenzymes. The
      activity of ALP isoenzymes depends on the method. The buffer systems of Reflotron
      ALP and Hitachi ALP are different. Significant exceeding of the reference range
      was reliably detected. In this investigation the study results for heparinized
      whole blood, heparinized plasma and serum are approximately the same.

PMID- 9931998
TI  - [Determination and clinical relevance of fecal pancreatic elastase in dogs].
AB  - The determination of faecal pancreatic elastase 1 is a reliable test for the
      diagnosis of chronic pancreatic diseases in man due to its high sensitivity and
      specificity (93%). A clinical study was performed to investigate the
      detectability of canine faecal pancreatic elastase with polyclonal anti human
      pancreatic elastase 1 antibodies in 52 dogs with chronic diarrhoea and weight
      loss. To assess the diagnostic value of this parameter for the diagnosis of
      exocrine pancreatic insufficiency (EPI) in dogs faecal chymotrypsin activity was
      determined and serum trypsin-like immunoreactivity (TLI) concentration was
      measured within the Ceruletid test in all patients. The study revealed that
      canine faecal pancreatic elastase cross reacts with polyclonal anti human
      pancreatic elastase 1 antibodies. In comparison with the results of the other
      pancreas tests it was proved that the concentration of canine faecal pancreatic
      elastase determined by rocket immunoelectrophoresis is highly sensitive for EPI
      in dogs (sensitivity 100%) but there are species differences in specificity
      between man and dog (specificity 56.5%).

PMID- 9931999
TI  - [Insects as a possible source of new antibiotics. Products produced by insects
      and their practical importance].

PMID- 9932000
TI  - [The epidemiology of Lyme borreliosis].
AB  - Lyme borreliosis (LB) is a multisystem disease caused by infection with Borrelia
      burgdorferi sensu lato (B.b). LB is the most common human tick-borne disease,
      transmitted principally by species of Ixodes ricinus in Europe, I. persulcatus in
      Eurasia, I. scapularis and I. pacificus in North America. B.b has been isolated
      or detected in 24 different species of mammals or birds. The B31 strain of
      B.burgdorferi sensu stricto is predominant in United States and in Europe B.
      garinii, B. afzelii and B. burgdorferi sensu stricto.

PMID- 9932001
TI  - [The potential risk factors associated with acute viral hepatitis in children
      under 5 years old].

PMID- 9932002
TI  - [The clinico-epidemiological aspects of HIV infection in 167 children
      nonmaternally infected who have died with a diagnosis of AIDS].
AB  - The aim of this study was to evaluate the clinical and epidemiological
      particularity of pediatrics nosocomial HIV infection. Our study group consists of
      167 HIV serum-positive nonmaternally infected children who died of AIDS in 1990
      1997 (inclusive) in Colentina Hospital of Infections Diseases--Bucharest. Fifty
      per cent of institutionalized children and 28% of family children died in the
      first two years of life. About 80% of children were revealed too late as HIV
      infected. It has been observed a relatively high prevalence values for: multiple
      or recurrent pneumonia--74.8%, recurrent or chronic diarrhea--87.4%,
      encephalopathy--65.8%, weight-growth deficiency--100%, disseminated or
      extrapulmonary tuberculosis--13.8%, HBsAg carriage--59.8%; and low prevalence
      values for: lymphoid interstitial pneumonia--16.5%, Pneumocystis carinii
      pneumonia--11.4%, cytomegalovirus diseases--1.8%, cryptosporidiosis--1.8%. The
      evolution of HIV infection (weight-growth deficiency and encephalopathy) were
      aggravated in hospitalised children (especially, in the first two years of life).
      Nutrition and hygiene care factors positively influence the evolution of HIV
      infection. Multiple or recurrent pneumonia are out of an important prognostic
      value in the appreciation of SIDA evolution. The incidence and severity of
      tuberculosis increased at older children. The too late diagnostic of HIV
      infection had unfavourable influence upon the life expectancy of children.

PMID- 9932003
TI  - [Epidemiological data on toxoplasmosis. The aspects of congenital toxoplasmosis].
AB  - The aim of the present study was to get a real image about Toxoplasma gondii
      infection of pregnant woman and the consequence for her child in Moldavia area.
      There were studied: 224 pregnant women with pathological pregnancies comparing
      with 347 apparently healthy pregnant women; 1422 newborns; 223 children with
      mental retardation and visual pathology comparing with 129 apparently healthy
      children. There were used the following serological methods: indirect
      immunofluorescent assay, direct agglutination test, immunosorbent agglutination
      assay (ISAGA). The following results were obtained: 1) a high sero-prevalence of
      T. gondii antibodies among pregnant women (43.9%)--most of them being chronic
      infections; 2) 0.6% pregnant women with acute toxoplasmosis in the first
      trimester of their pregnancies, situation with great danger for the unborn child;
      3) a 7.1% degrees of participation of T.gondii infection to the etiology of
      spontaneous abortion; 4) a high seroprevalence of T.gondii antibodies among
      children with mental retardation (66.4%) and visual pathology (37.4%) comparing
      with the group of apparently healthy children (9.3%). The conclusion resulting
      from this data is that toxoplasmosis demands more attention from our medical
      world, a national program of prophylaxis including a large screening of pregnant
      women and/or newborns being able to prevent the severe damages due to congenital
      toxoplasmosis.

PMID- 9932004
TI  - [Seroepidemiological studies on the immunization of the population against
      species of the genus Bordetella in 1996-1997].

PMID- 9932005
TI  - [The determination of the viral markers of the hepatitis B virus and protein p53
      in liver biopsy samples].
AB  - The X gene product of the hepatitis B virus (HBV) genome functions as a
      transactivating element and it is considered as an essential factor for
      establishing chronic infection as well as for hepatocarcinogenesis. Its
      interaction with the product of the p53 tumor suppressor gene could be
      responsible for the intensification of cellular proliferation. We assessed the
      presence of X protein in biopsy samples of chronic hepatitis (CH), cirrhosis
      (CiH) and hepatocellular carcinoma (HCC) tissues comparing to the presence of
      other viral markers (HBcAg, HBsAg) using immunohistochemical methods. We sought
      the expression of p53 gene in the same tissue samples and analysed the
      possibility of its accumulation in detectable quantity at different stages of the
      disease. Our results indicate a higher positivity for the X protein than for HBs
      and HBc antigens (p < 0.05). HBx expression in liver cells during chronic HBV
      infection may be a prognostic marker for the development of HCC. The p53 protein
      was not detectable in the majority of non-malignant tissues; thus its
      inactivation seems to be more likely a late event in carcinogenesis.

PMID- 9932006
TI  - [The bactericidal and bacteriostatic capacities of the amniotic fluid as a
      function of the time from membrane rupture].

PMID- 9932008
TI  - [Clinico-bacteriological correlations in necrotizing fasciitis].
AB  - The authors analyze under the aspect of data offered by medical literature, the
      clinical aspects and occurrence of the microbial flora in the necrotizing
      fasciitis. The clinical symptoms are presented in correlation with the aerobic,
      anaerobic and mixed bacterial specificity with the purpose of a suitable
      antibacterial therapy. Further, there are presented certain aspects of cutaneous
      "bubbly" lesions connected with the microbial flora in the NF.

PMID- 9932007
TI  - [The incidence of microbial and fungal species associated with Trichomonas
      vaginalis infection].

PMID- 9932009
TI  - [An update on cholera infection].

PMID- 9932010
TI  - [The vir regulon--a new epidemiological marker for Streptococcus pyogenes].

PMID- 9932011
TI  - [Diphtheria in the city of Iasi 1894-1995].

PMID- 9932012
TI  - Role of intestinal chemoreception in the induction of gastrointestinal
      sensations.
AB  - Both distension of the stomach and activation of small intestinal chemoreceptors
      by nutrients have been implicated in the induction of postprandial sensations.
      Studies were performed in healthy human subjects to investigate the roles of
      gastric distension and activation or inhibition of small intestinal
      chemoreceptors in the generation of pleasant (fullness) and unpleasant (nausea,
      pain) gastrointestinal sensations. The proximal stomach was distended by
      inflating a balloon attached to a gastric tube with air, while the duodenum was
      perfused with nutrient solutions, either lipid or carbohydrates. In additional
      experiments, the upper small intestinal mucosa was anaesthetised by topical
      anaesthesia or an antagonist to cholecystokinin (CCK)-A receptors given
      intravenously during duodenal lipid infusion. Gastric distension induced
      sensations of epigastric pressure and pain, while during duodenal infusion of
      both carbohydrate and lipid, fullness was described as a more meal-like
      sensation. In addition, lipid but not carbohydrate infusion resulted in
      significant nausea. The sensory experience evoked by lipid was diminished by both
      topical mucosal anaesthesia and CCK-A receptor blockade. The data provide
      evidence for the involvement of small intestinal chemoreceptors in the modulation
      of sensations induced by gastric distension.

PMID- 9932013
TI  - Glucose and maltodextrin in enteral diets have different effects on jejunal
      absorption of nutrients, sodium and water and on flow rate in mini pigs.
AB  - In four mini pigs a segment of the proximal jejunum was temporarily isolated and
      perfused with two enteral diets containing isocaloric amounts either of glucose
      or maltodextrin. With regard to total energy, the diets were composed of 60%
      carbohydrate, 20% protein and 20% fat. The perfusion rates were 1, 2, 4, 6, and 8
      kcal/min. Absorption of glucose and fat from the maltodextrin diet was
      significantly greater than from the glucose diet, whereas absorption of protein
      was only slightly enhanced. A net water absorption occurred at perfusion of the
      isotonic solution with maltodextrin. Perfusing the hypertonic glucose diet, water
      was secreted. Therefore the flow rate increased from oligomer to monomer glucose
      source. With enhanced flow rate sodium secretion increased. However, the sodium
      concentration of the effluent was determined more by the transepithelial water
      movement than by the sodium secretion. The present results indicate that in
      enteral diets with interactions among different nutrients there is a 'kinetic
      advantage' in glucose absorption from maltodextrin compared to glucose. However,
      the reduced flow rate of the maltodextrin diet due to the lower osmolality
      contributed to the enhanced absorption.

PMID- 9932014
TI  - Strain gauge transducer technique for investigation of the pathophysiology of
      postoperative colonic ileus in awake rats.
AB  - Postoperative inhibition of colonic motility is a major contributor to
      postoperative ileus, but only limited information is available on its
      pathophysiology. We developed a model to record perioperative gastrointestinal
      motility in awake rats and investigated the effect of nitric oxide (NO) synthesis
      blockade on postoperative colonic ileus in rats. Rats were equipped with an i.v.
      catheter. Two strain gauge transducers were sutured to the colon, and the effects
      of NO synthesis blockade on postoperative colonic motility were investigated. NO
      synthesis blockade slightly increased baseline colonic motility. Abdominal
      surgery profoundly inhibited colonic motility. Blockade of NO synthesis did not
      prohibit intraoperative inhibition of colonic motility, but significantly
      hastened recovery of postoperative colonic ileus compared to vehicle. We
      established a model to record gastric, small intestinal and colonic motility in
      awake rats postoperatively. Laparotomy and short manipulation of the cecum
      produced a prolonged inhibition of colonic motility. Inhibition of NO synthesis
      improved recovery of postoperative colonic motility, indicating that NO partly
      mediates postoperative colonic ileus in rats.

PMID- 9932015
TI  - Molecular physiology of colonic epithelial sodium absorption.
AB  - The colon is the final site for fluid and electrolyte conservation in the
      gastrointestinal system. Active absorption of sodium ions generates driving
      forces for the movement of fluid and other electrolytes, and is under hormonal
      control of mineralocorticoids for maintaining body homeostasis. Sodium is
      absorbed through a transcellular route, and the main regulatory sites are
      epithelial sodium channels (ENaCs), located in the apical cell membrane. Recently
      these channels have been cloned, and were also found in other cells from kidney
      to lung. They belong to a newly discovered ancient superfamily of channels which
      dates back in evolution to nematodes. Physiological investigations of the
      molecular diversity of this channel family not only provides new information of
      an important group of biomolecules, but opens up routes for the understanding and
      treatment of various diseases ranging from kidney failure to high blood pressure.

PMID- 9932016
TI  - Temporal analysis of feeding behavior in miniature pigs.
AB  - The feeding behavior of four Munich miniature pigs (29-43 kg) housed in pairs of
      two, was observed for two consecutive weeks. Pigs were conditioned to operate a
      computer-controlled recording system equipped with feeders delivering a precise
      food release per response and were then fed ad libitum. In addition to the
      descriptive analysis of feeding behavior, Walsh-Fourier Spectral Analysis was
      utilized to investigate the temporal patterns of food ingestion and the
      synchronisation of feeding patterns between the animals housed together. The pigs
      had up to 48% of their daily energy intake during the dark cycle and there was a
      substantial reduction of food intake from the first to the second week.
      Furthermore, pigs housed together synchronized feeding behavior from week 1 to
      week 2. The recording system has been shown to be highly reliable and valid and
      provides an excellent tool for the investigation of ingestive behaviors in
      miniature pigs.

PMID- 9932017
TI  - Structural and functional organization of the enteric nervous system in the
      stomach.
AB  - This report summarises some features of the gastric enteric nervous system in the
      guinea-pig model. Particular attention has been paid to relations between
      neurochemical properties, electrophysiological and putative function of enteric
      neurones. (1) Cholinergic and nitrergic neurones form separate neuronal
      populations. (2) Ascending neurones outnumbered descending ones. (3) Transmitter
      phenotype and projection were related: cholinergic neurones were primarily
      ascending while nitrergic neurones were mainly descending. (4) The neurochemical
      code, i.e. the transmitter colocalisation, could be related to the function of
      enteric neurones. Colocalisation of substance P and/or enkephaline in cholinergic
      neurones was characteristic for ascending excitatory muscle neurones. Descending
      inhibitory muscle neurones were nitrergic often colocalising the neuropeptides
      neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In the intrinsic
      innervation of the gastric mucosa NPY/VIP was abundant and colocalised in
      ascending cholinergic as well as descending nitrergic neurones. (5) The vast
      majority of ascending and descending interneurones were cholinergic and often
      colocalised NPY. (6) The majority of descending mucosa and descending inhibitory
      muscle neurones were tonically-firing neurones. Our results revealed the
      characteristics of some neural components within the enteric nervous system of
      the stomach which are involved in modulation of mucosa and muscle functions. It
      may be concluded that muscle and mucosa functions are under the control of the
      enteric nervous system which contains distinct populations responsible for motor
      and secretory activity.

PMID- 9932018
TI  - Mesenteric afferent sensitivity to cholecystokinin and 5-hydroxytryptamine.
AB  - The present electrophysiological investigation examines the effect of CCK and 5
      hydroxytryptamine on gastrointestinal afferent fibre discharge. 5-HT markedly
      stimulated mesenteric afferents. The response was transient (< 10s) and mediated
      by 5-HT3 receptors as demonstrated by the action of 2-methyl-5-HT and antagonism
      by granisetron. CCK was also a potent stimulus to mesenteric afferents causing a
      long-lasting (> 30s) increase in excitability. The response to CCK was mediated
      via the CCKA receptor as shown by the antagonistic action of devazepide. At doses
      of granisetron and devazepide which completely block the response to exogenous 5
      HT and CCK, the afferent fibres still responded to both mechanical and chemical
      stimulation of the mucosa. Thus products of enteroendocrine cells can have
      profound effects on mucosal afferent sensitivity but do not play an obligatory
      role in afferent signal transduction.

PMID- 9932019
TI  - Neurogastroenterology--information processing from the viscera to the brain in
      humans.
AB  - With the many new investigational possibilities allowing access to the gut-brain
      axis in humans, new techniques, mainly from neurology, as well as
      interdisciplinary approaches, have produced insights into afferent information
      processing from the gut to the brain. They have become research tools in recent
      years, but will eventually become clinical tools for diagnostic purposes in the
      future. Gut-brain interactions may be seen at different levels: rather simple
      research models such as recordable perception and pain, on the one hand, can be
      contrasted and/or supplemented with neurological stimulation and imaging
      techniques, and clinical models such as spinal cord injury. All have contributed
      to the development of a new subspecialty in medicine, neurogastroenterology.

PMID- 9932020
TI  - Forestomach motility in llamas and camels.
AB  - Major aspects of forestomach anatomy in llamas and camels are described. The
      pattern of forestomach motility is a succession of motoric cycles, consisting of
      A- and B-contraction sequences and a pause. Respective differences between llamas
      and camels are discussed. Observations on regulation of motility are mentioned.
      Occurrences and courses of rumination and eructation within the motility cycles
      are emphasized. Motility of the forestomach achieves a selective retention of
      feed particles in the forestomach; a long retention time is a prerequisite for an
      effective microbial digestion, especially of poor quality feed.

PMID- 9932022
TI  - [Nutritional counseling--a wide field for the pharmacist].

PMID- 9932021
TI  - [Alteration of rendering and meat hygiene legislation in the course of the
      BSE/TSE crisis. Validity of decisive legal provisions (1)].
AB  - The decisive European legal provisions to fight bovine sponfiform encephalopathy
      in the context of the rendering and meat-hygiene legislation are the Commission
      Decisions 96/449/EC "on the approval of alternative heat treatment systems for
      processing animal waste with a view to the inactivation of spongiform
      encephalopathy agents" and 97/534/EC "on the prohibition of the use of material
      presenting risks as regards transmissible spongiform encephalopathies". Both
      decisions are based on Council Directives which do not provide the necessary
      authorization for these decisions by the Commission. Consequently, both have to
      be regarded as legally invalid. Furthermore, the legal acts to convert these
      decisions into German law (Rendering Plants Regulation and Meat-Hygiene
      Regulation) have to be considered invalid--partly due to formal and partly due to
      factual reasons. Because of the thus created legal uncertainty the legal
      provisions in question can only come fully into force after the elimination of
      this specifically described legal shortcomings or after clarification of the
      legal situation by the responsible courts.

PMID- 9932023
TI  - [Retinoids. A new drug group with many possible uses?].

PMID- 9932024
TI  - [What is adequate nutrition?].

PMID- 9932025
TI  - [Bilharziosis (schistosomiasis) of the bladder. Pathogenesis, therapy and
      uroprotective measures].

PMID- 9932026
TI  - [What role does homocysteine play in vascular diseases?].

PMID- 9932028
TI  - [The evolution of the tuberculosis endemic in 1997 in Romania].

PMID- 9932029
TI  - [The monitoring of delayed-release theophylline therapy in bronchial asthma in
      children by determining the salivary concentration].
AB  - Long-term therapy with slow-release theophylline is compulsory to be monitorized
      by measuring serum concentration of the drug. This is due to the narrow
      therapeutically index of theophylline for monitoring the long term therapy with
      this drug, and to establish the correlation between the serum and saliva
      concentration of theophylline. The study group was represented by 13 children
      with asthma, with the age between 2 and 13 years that received theophylline in an
      average dosage of 15.2 mg/kg/24 hours. In all of them there were obtained two
      paired simultaneous samples of venous blood and of saliva, at 4 hours and at 8
      hours respectively, after the administration of theophylline. For facilitate the
      saliva sampling, its production was stimulated by applying citric acid on the
      tongue and aspiration with a sterile syringe. For measuring the serum and saliva
      levels of the drug it was used mass spectrometry with 15N-theophylline as
      internal standard. Serum theophylline concentration varied between 6.56 +/- 4.48
      micrograms/ml at 8 hours after drug administration and respectively 7.45 +/- 3.94
      micrograms/ml at 4 hours after drug administration. Saliva concentrations of
      theophylline varied between 4.18 +/- 2.40 micrograms/ml at 8 hours after drug
      administration and respectively 4.66 +/- 2.39 micrograms/ml at 4 hours after drug
      administration. The average ratio between serum and saliva concentration in the
      24 paired samples was 1.62 +/- 0.18. The intraindividual variation of this ratio
      was 8.64%.

PMID- 9932030
TI  - [A survey of the perception of COPD by physicians (I)].
AB  - Observing the great importance of COPD nowadays, the authors aimed to check the
      doctors' opinions concerning this matter. 300 questionnaires including 53
      questions were mailed to doctors in the whole country. 103 filled-in
      questionnaires (34.34%) were recovered from 36 pulmonologists (PNF), 24 internal
      medicine specialists (Int) and 43 general practitioners (Gen). One could
      sometimes note important differences between the answers depending upon the
      specialty. Thus, the quality of the COPD assistance is considered unsatisfactory
      by many PNF. All doctors consider COPD as a concerning problem. The diagnosis is
      always established using clinical criteria (cough, dyspnea). There are
      differences between the doctors in using the X-ray and the lung function tests as
      diagnosis criteria, due to accessibility to these tests, but also to the
      interpretation. COPD may often be mixed up with other obstructive diseases,
      especially asthma, and many doctors include also the obstructive post-TB
      syndromes in COPD. All the doctors, no matter the specialty, consider themselves
      capable of diagnosis COPD. Despite the scarce participation to the questionnaire
      (due to lack of courage or of interest), the questionnaire can make up an image
      of the concern of the Romanian doctors for the COPD medical assistance, making
      also the consequences of the limited access to the newest informations.

PMID- 9932031
TI  - [Pulmonary hyperinflation. The functional and clinico-radiological criteria,
      mechanisms and surgery to reduce lung volume in severe emphysema].

PMID- 9932032
TI  - [Empyema caused by Corynebacterium striatum].
AB  - We present the case of a patient, male aged 21 years, admitted in our hospital
      for an empyema. A strain of C. striatum has been isolated from the pus sampled
      through the drainage tube. The isolate was identified on Api Coryne gallery (bio
      Merieux S.A., France) (identity 97.1%). The disk sensitivity test showed
      sensitivity to penicillin, cefotaxime, amoxicillin-clavulanate and resistance to
      rifamycin, kanamycin, pefloxacin, ofloxacin, chloramphenicol, erythromycin and
      lincomycin. The arguments involving the isolated strain as the aetiological agent
      were: 1. The bacterium was isolated in pure culture and in significant quantity
      and 2. The existence of a favourizing clinical condition for an infection caused
      by a normal resident of the skin.

PMID- 9932033
TI  - [The therapeutic considerations in the "overlap syndrome"].
AB  - The authors describe two cases of "overlap syndrome", emphasizing the
      difficulties of detecting, diagnosing and treating these cases. This paper allows
      us to review the medical works, trying to find out some answers to the
      therapeutical problems faced in these two cases.

PMID- 9932034
TI  - [Recommendations for the staging of bronchopulmonary cancer].

PMID- 9932035
TI  - [Measures to prevent and control the transmission of tuberculous infection,
      especially multiresistant tuberculosis].

PMID- 9932036
TI  - [Tobaccology].

PMID- 9932040
TI  - [Legislative measures against tobacco and their impact on decreasing tobacco
      consumption].

PMID- 9932042
TI  - National hospital discharge survey: annual summary, 1996.
AB  - OBJECTIVES: This report presents national estimates of the use of non-Federal
      short-stay hospitals in the United States during 1996 and selected trend data.
      Estimates are provided by demographic characteristics of patients discharged,
      geographic region of hospitals, conditions diagnosed, and surgical and
      nonsurgical procedures performed. Measurements of hospital use include number and
      rate of discharges and days of care, and the average length of stay. METHODS: The
      estimates are based on data collected through the National Hospital Discharge
      Survey (NHDS). The survey has been conducted annually by the National Center for
      Health Statistics (NCHS) since 1965. In 1996, data were collected for
      approximately 282,000 discharges. Of the 507 eligible non-Federal short-stay
      hospitals in the sample, 480 (95 percent) responded to the survey. Diagnoses and
      procedures are coded according to the International Classification of Diseases,
      9th Revision, Clinical Modification, or ICD-9-CM.

PMID- 9932043
TI  - Ninety-nine years later.

PMID- 9932044
TI  - Multistate licensure?

PMID- 9932047
TI  - Right drug, wrong dose.

PMID- 9932048
TI  - Using agonist-antagonist opioids and antagonist drugs.

PMID- 9932050
TI  - Whistleblowing. Does the law protect you?

PMID- 9932051
TI  - Emergency! Anaphylaxis.

PMID- 9932053
TI  - Systemic lupus erythematosus.

PMID- 9932052
TI  - To speak or not to speak? Self-disclosure with patients.

PMID- 9932054
TI  - Understanding therapeutic drug monitoring.

PMID- 9932055
TI  - The road to adventure. Dreaming of the day you can travel ... with pay? Here's
      how!

PMID- 9932056
TI  - Professional growth through volunteerism.

PMID- 9932057
TI  - Nursing research comes into its own.

PMID- 9932058
TI  - Books of the year. The most valuable texts of 1998 as chosen by AJN's panel of
      judges.

PMID- 9932059
TI  - From nurse to novelist.

PMID- 9932060
TI  - The health care continuum. How to make the business of nursing work for you.

PMID- 9932062
TI  - Preventing needlestick injuries.

PMID- 9932061
TI  - The first gynecologic exam.

PMID- 9932063
TI  - When you're the health care consumer.

PMID- 9932064
TI  - Lawyers, heal thyselves (fat chance!)

PMID- 9932065
TI  - Collaborative ocular melanoma study group.

PMID- 9932066
TI  - After the grant runs out. Long-term provider health maintenance compliance using
      a computer-based tracking system.
AB  - OBJECTIVE: To measure long-term provider (physicians and physician's assistants)
      health maintenance compliance 4 years after the completion of a grant-funded
      project to improve provider compliance by using a computer-based health
      maintenance tracking system. DESIGN: Cross-sectional comparison of provider
      health maintenance compliance for patients receiving computer-based health
      maintenance tracking in 1992 and 1996. SETTING: Rural, multiple-office,
      nonprofit, fee-for-service family practice. MAIN OUTCOME MEASURES: Overall
      provider compliance with the common elements of the health maintenance protocols
      in 1992 and 1996. Provider compliance with specific, individual preventive
      interventions was compared. RESULTS: Overall provider compliance was 83% in 1996,
      compared with 80% in 1992. This difference was statistically significant (P =
      .05) but not clinically significant. Provider compliance was significantly higher
      in 1996 for 3 procedures: blood pressure determination, tetanus-diphtheria
      immunization, and weight. It was unchanged for 5 procedures: clinical breast
      examination, mammography, Papanicolaou smears, cholesterol determination, and
      fecal occult blood testing for colon cancer. Provider compliance with obtaining a
      history of tobacco use declined. CONCLUSION: Improvements in provider health
      maintenance compliance associated with installation of a computer-based health
      maintenance tracking system were maintained 4 years after cessation of the formal
      research intervention.

PMID- 9932067
TI  - Tools to improve documentation of smoking status. Continuous quality improvement
      and electronic medical records.
AB  - BACKGROUND: Despite the deleterious effects of smoking on the nation's health and
      evidence that smoking cessation advice by family practice physicians is cost
      effective, self-sustaining office systems to identify smokers in primary care
      clinics have been difficult to establish. We worked on a continuous quality
      improvement project group, aided by an electronic medical record, to design a
      system to document and periodically update smoking status in a consistent place
      in the medical record. INTERVENTION: Using the continuous quality improvement
      plan-do-study-act cycle, a 7-member group worked with nursing staff to define
      roles, routines and responsibilities for medical assistants to screen for and
      document 1 of 4 categories of smoking status in the major problem list of the
      electronic medical record for at least 80% of patient appointments. Screening
      rate was tracked monthly by means of the electronic medical record and feedback
      was given to staff. RESULTS: The screening rate rose from 18.4% to 80.3% within 2
      weeks after the system was implemented and was maintained for 19 months. An
      additional benefit was an increased rate of smoking cessation counseling
      documented by providers, from a baseline rate of 17.1% to 48.3%. CONCLUSIONS: A
      continuous quality improvement group process aided by an electronic medical
      record is useful to develop a self-sustaining office system to screen, document,
      and periodically update smoking status in a consistent place in the medical
      record. Although screening for and documenting smoking status are only the first
      step toward helping patients stop smoking, it is an important one.

PMID- 9932069
TI  - Declining visits to primary care physicians?

PMID- 9932068
TI  - Trends in adult visits to primary care physicians in the United States.
AB  - BACKGROUND: Although numerous changes are apparent in the US health care system,
      little is known about how these changes have altered the work of primary care
      physicians. METHODS: We analyzed a nationally representative sample of 136,233
      adult office visits to general internists, general practitioners, and family
      physicians contained in the 1978 through 1981, 1985, and 1989 through 1994
      National Ambulatory Medical Care Surveys. Annual sample sizes varied between 5662
      and 19,977 visits. Measures included the characteristics of patients presenting
      to primary care physicians, physician activities during these visits, and the
      disposition of the visits to primary care physicians. RESULTS: Visits to primary
      care physicians have diminished as a proportion of all adult visits from 52% in
      1978 to 41% in 1994. Dramatic trends in adult primary care included the growing
      racial or ethnic diversity of patients, the doubling (since 1985) of health
      maintenance organization coverage, increased provision of prevention services,
      changes in the most common medications, and an 18% increase in the duration of
      adult visits to primary care physicians. CONCLUSIONS: Trends in primary care
      practice reflect changes in society and in the US health care system, including
      demographic changes, an emphasis on prevention, and the growth of managed care.
      The increasing role of managed care, with its emphasis on increased productivity,
      appears at odds with primary care physicians' increasing responsibility for
      prevention and the associated increase in the duration of primary care visits.

PMID- 9932070
TI  - Health-related quality of life and symptom profiles of female survivors of sexual
      abuse.
AB  - OBJECTIVES: To determine the association between severity of sexual abuse and
      psychiatric or medical problems in a sample of female patients from primary care
      medical settings and to assess the relationship between sexual abuse severity and
      health-related quality of life before and after controlling for the effects of a
      current psychiatric or medical diagnosis. DESIGN: Structured interview and self
      report questionnaire. SETTING: Three family practice outpatient clinics.
      SUBJECTS: A total of 252 women selected by somatization status using a screen for
      unexplained physical symptoms. MAIN OUTCOME MEASURES: Patient assessment after
      administering the Medical Outcomes Study 36-item Short-Form Health Survey and
      self-report medical problems questionnaire; the quality-of-life scale developed
      by Andrews and Withey; Diagnostic and Statistical Manual of Mental Disorders,
      Third Edition, Revised, diagnoses and symptom counts from the Diagnostic
      Interview Schedule; the Dissociative Experiences Scale; and the modified
      Dissociative Disorders Interview Schedule. RESULTS: A history of sexual abuse is
      associated with substantial impairment in health-related quality of life and a
      greater number of somatized symptoms (P < .001), medical problems (P < .01), and
      psychiatric symptoms and diagnoses (P < .001). In regression analyses, sexual
      abuse severity was a significant predictor of high scores on 6 of the 8 subscales
      of the Medical Outcomes Study Short-Form Health Survey (P < .05) and all of the
      quality-of-life subscales developed by Andrews and Withey (P < .01), with average
      decrements of up to 0.41 SDs for moderately abused women and 0.56 SDs for
      severely abused women. Furthermore, sexual abuse severity remained a significant
      predictor of high scores on the subscales mental health (P < .05), social
      functioning (P < .05), and quality of life (P < .05), even after adjusting for
      the presence of several common psychiatric diagnoses. CONCLUSIONS: Female primary
      care patients with a history of sexual abuse have more physical and psychiatric
      symptoms and lower health-related quality of life than those without previous
      abuse. In addition, a linear relationship exists between the severity of sexual
      abuse and impairment in health-related quality of life, both before and after
      controlling for the effects of a current psychiatric diagnosis.

PMID- 9932071
TI  - Accessibility of primary care physicians' offices for people with disabilities.
      An analysis of compliance with the Americans With Disabilities Act.
AB  - OBJECTIVE: To determine if primary care physicians are in compliance with the
      Americans With Disabilities Act of 1990 (ADA) and to what extent offices of
      primary care physicians are usable for persons with disabilities. DESIGN: Cross
      sectional survey. SETTING: Members listed in the Harris County (Texas) Medical
      Society roster. SUBJECTS: Sixty-two general practitioners, family practitioners,
      internists, and obstetrician-gynecologists. MAIN OUTCOME MEASURE: A 15-page
      questionnaire with 57 items and 136 variables. RESULTS: Eleven (18%) of the
      primary care physicians in this study were unable to serve their patients with
      disabilities in the last year for reasons that could be interpreted as
      noncompliant with the ADA. Two physicians (3%) had offices that patients with
      disabilities could not enter because of physical barriers, and 1 physician (2%)
      had inaccessible equipment. Fourteen physicians (22%) were improperly referring
      patients with disabilities although they generally treat such patients. In
      measuring the level of compliance with regard to structural features that enhance
      the accessibility of the physicians' offices, only 8 (13%) had a low level of
      compliance. Thirty-nine (63%) of the physicians supplied auxiliary aids and
      services to their patients with disabilities. The most common aid was printed
      materials. CONCLUSIONS: A substantial portion of primary care physicians' offices
      are not in compliance with the ADA, and some informational tools will be required
      to inform physicians about the nondiscriminatory requirements of the statute.

PMID- 9932072
TI  - Costs and outcomes of PAPNET secondary screening technology for cervical
      cytologic evaluation. A community hospital's experience.
AB  - OBJECTIVE: To determine the effectiveness of and costs associated with
      semiautomated rescreening of Papanicolaou smears with negative findings at a
      community hospital. DESIGN: A prospective study of 1200 Papanicolaou smear slides
      with negative findings using the PAPNET screening system (Neuromedical Systems,
      Incorporated, Suffern, NY). SETTING: Community hospital laboratory. PATIENTS:
      Patients with negative findings on Papanicolaou smears who agreed to have their
      smears reviewed using PAPNET. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Results
      of rescreening and resources involved in processing the PAPNET review. RESULTS:
      Screening with PAPNET identified 8 patients with atypical squamous cells of
      undetermined significance (ASCUS) that were not diagnosed on initial screening,
      yielding a false-negative rate in our laboratory of 0.7% for ASCUS. No low- or
      high-grade squamous intraepithelial lesions were identified. Based on our
      laboratory processing 6000 Papanicolaou smears a year, at $19 per slide, it would
      cost our laboratory $102,600 for PAPNET review of all smears with negative
      findings. In contrast, the estimated cost to have another cytotechnologist review
      all such smears manually would cost $11,977. The rate of changed diagnoses in the
      PAPNET group was similar to the rate in our standard rescreening of 10% of all
      smears with negative findings. Mean turnaround time for a PAPNET screen was 13.9
      days, compared with 3.9 days for manual review. CONCLUSIONS: For a laboratory
      with a low percentage of smears with abnormal findings, a quality
      cytotechnologist and pathologist, and required quality assurance standards in
      place, PAPNET may not improve appreciably the pick-up rate for missed cervical
      lesions, and may add significantly to the cost and turnaround time of cytologic
      evaluation of cervical smears.

PMID- 9932073
TI  - Reducing mortality due to cervical cancer. PAPNET fails the test.

PMID- 9932074
TI  - Primary care physicians' approach to depressive disorders. Effects of physician
      specialty and practice structure.
AB  - BACKGROUND: Because primary care physicians (PCPs) are the initial health care
      contact for most patients with depression, they are in a unique position to
      provide early detection and integrated care for persons with depression and
      coexisting medical illness. Despite this opportunity, care for depression is
      often suboptimal. OBJECTIVE: To better understand how to design interventions to
      improve care, we examine PCPs' approach to recognition and management and the
      effects of physician specialty and degree of capitation on barriers to care for 3
      common depressive disorders. METHODS: A 53-item questionnaire was mailed to 3375
      randomly selected subjects, divided equally among family physicians, general
      internists, and obstetrician-gynecologists. The questionnaire assessed reported
      diagnosis and treatment practices for each subject's most recent patient
      recognized to have major or minor depression or dysthymia and barriers to the
      recognition and treatment of depression. Eligible physicians were PCPs who worked
      at least half-time seeing outpatients for longitudinal care. RESULTS: Of 2316
      physicians with known eligibility, 1350 (58.3%) returned the questionnaire.
      Respondents were family physicians (n = 621), general internists (n = 474), and
      obstetrician-gynecologists (n = 255). The PCPs report recognition and evaluation
      practices related to their most recent case as follows: recognition by routine
      questioning or screening for depression (9%), diagnosis based on formal criteria
      (33.7%), direct questioning about suicide (58%), and assessment for substance
      abuse (68.1%) or medical causes of depression (84.1%). Reported treatment
      practices were watchful waiting only (6.1%), PCP counseling for more than 5
      minutes (39.7%), antidepressant medication prescription (72.5%), and mental
      health referral (38.4%). Diagnostic evaluation and treatment approaches varied
      significantly by specialty but not by the type of depression or degree of
      capitation. Physician barriers differed by specialty more than by degree of
      capitation. In contrast, organizational barriers, such as time for an adequate
      history and the affordability of mental health professionals, differed by degree
      of capitation more than by physician specialty. Patient barriers were common but
      did not vary by physician specialty or degree of capitation. CONCLUSIONS: A
      substantial proportion of PCPs report diagnostic and treatment approaches that
      are consistent with high-quality care. Differences in approach were associated
      more with specialty than with type of depressive disorder or degree of
      capitation. Quality improvement efforts need to (1) be tailored for different
      physician specialties, (2) emphasize the importance of differentiating major
      depression from other depressive disorders and tailoring the treatment approach
      accordingly, and (3) address organizational barriers to best practice and
      knowledge gaps about depression treatment.

PMID- 9932076
TI  - Bacterial resistance due to antimicrobial drug addiction among physicians. Time
      for a cure!

PMID- 9932075
TI  - Strategies for dealing with amoxicillin failure in acute otitis media.
AB  - Acute otitis media is the most common bacterial infection in pediatric patients.
      The predominant pathogens of acute otitis media are Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis. Traditionally, amoxicillin has
      been the first-line therapeutic choice for patients with uncomplicated acute
      otitis media. However, with the increasing isolation of beta-lactamase-producing
      organisms and penicillin-resistant S pneumoniae, the frequency of amoxicillin
      treatment failures also appears to be increasing. Several issues should be
      considered when alternative antibiotics are selected to treat amoxicillin
      failures, such as the most likely pathogens with their susceptibility patterns,
      and antibiotic issues including clinical efficacy for specific pathogens, adverse
      reactions, palatability, dosing schedules, and cost. Consequently, enhanced beta
      lactamase stability, activity against penicillin-resistant S pneumoniae, and once
      or twice-daily dosing regimens must be considered when antibiotics are chosen
      for patients in whom amoxicillin therapy has failed.

PMID- 9932077
TI  - Medicine and public health. Whose agenda?
AB  - My grandfather was a general practitioner in a rural midwestern town during the
      first half of this century. His office consisted of a single examining room in
      the family home, a tiny waiting area, and little envelopes in which he dispensed
      medications. Patient hours were in the evening, no appointment necessary. Mostly,
      folks chatted in the living room with my grandmother while waiting to see
      "Grandpa Doc." My grandfather's nights often included trips to neighbors'
      kitchens to deliver babies. Days were time to serve as the county health officer,
      student health director for the local college, and organizer of the town's free
      clinic for indigent patients, based in the Presbyterian church.

PMID- 9932078
TI  - [Topoisomerases I: new targets for the treatment of cancer and mechanisms of
      resistance].
AB  - DNA topoisomerases I are ubiquitous enzymes that play a crucial role in DNA
      condensation, replication, transcription, and repair. Eukaryotic enzymes are
      highly conserved and specifically targeted by natural anticancer agents such as
      camptothecin and its derivatives. These drugs poison top 1 by inhibiting the
      enzyme via trapping of top 1 clivage complexes, which ultimately generate cell
      death. New camptothecin derivatives with better pharmacologic characteristics are
      under development. Understanding top 1 functions and structure will help to
      discover more specific and less toxic top 1 inhibitors in order to circumvent
      drug resistance.

PMID- 9932079
TI  - [Irinotecan pharmacokinetics].
AB  - The clinical pharmacokinetics of irinotecan (CPT11) can be described by a 2 or 3
      compartment model, a mean terminal half-life of 12 hours, a volume of
      distribution at steady state of 168 l/m2 and a total body clearance of 15 l/m2/h.
      Irinotecan is 65% bound to plasma proteins. The areas under the plasma
      concentration-time curve (AUC) of both irinotecan and active metabolite SN38
      increase proportionally to the administered dose, although interpatient
      variability is important. SN38 levels achieved in humans are about 100-fold lower
      than corresponding irinotecan levels, but these concentrations are important
      since SN38 is 100- to 1,000-fold more cytotoxic than the parent compound. SN38 is
      95% bound to plasma proteins. SN38 plasma decay follows closely that of the
      parent compound. Irinotecan is extensively metabolized in the liver. The
      bipiperidinocarbonylxy group of irinotecan is first removed by a carboxyesterase
      to yield the corresponding carboxylic acid and SN38. This metabolite can be
      converted into SN38 glucuronide by UDP-glucuronyltransferase (1.1 isoform). A
      recently identified metabolite is the 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1
      piperidino]-carbonyloxy-camptothecin (APC), which is formed by the action of
      cytochrome P450 3A4. Numerous other unidentified metabolites are detected in bile
      and urine. The mean 24 h irinotecan urinary excretion represents 17-25% of the
      administered dose, whereas SN38 and its glucuronide recovery in urine is minimal
      (0.5 and 6%, respectively). Irinotecan and SN38 pharmacokinetics are not
      influenced by prior exposure to the parent drug. Irinotecan and SN38 AUCs
      correlate significantly with leuko-neutropenia and sometimes with the intensity
      of diarrhea. Increased bilirubin levels appear to influence irinotecan total body
      clearance. The observation that most tumor responses were seen at the highest
      doses administered in phase I trials suggest a dose-response relationship with
      this drug. These pharmacokinetic-pharmacodynamic relationships may prove useful
      for a better clinical management of this drug aimed at a better control of
      toxicities and a better prediction of tumor response for the benefit of the
      individual patient.

PMID- 9932080
TI  - [Clinical activity spectrum of irinotecan].
AB  - Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a
      broad spectrum of clinical activity. Two main schedules have been studied and
      produce similar activity and side-effects: the "european" one--350 mg/m2 every 21
      days-, and the "japanese-north american" one where CPT11 is given at a weekly
      dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period.
      Activity was initially characterized in advanced colorectal cancers; response
      rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11
      months in patients failing fluoropyrimidine based chemotherapy--statistically
      improved as compared to best supportive care and infusional fluorouracil-, and 20
      30% in patients not previously treated. An interesting activity with response
      rates of 20-22% (increased to 65% in combination with CDDP) has been shown in
      relapsed cervix carcinomas; in gastric carcinomas response rates of 20% have been
      shown, reaching 48% in combination with CDDP. Response rates of 20-22%, increased
      to 40-60% when irinotecan was associated to CDDP have been reported in non small
      cell lung cancer and esophagal carcinomas. Further studies are needed for other
      GI tract cancers, ovarian and head and neck carcinomas while minimal or no
      clinically meaningful activity has been reported in advanced breast cancer, and
      haematological malignancies. Irinotecan can be combined to fluoropyrimidines,
      raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide,
      vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21
      days. Most of these combinations have an additive or supra additive activity. Its
      mechanism of action, the spectrum of activity and the acceptable risk-benefit
      ratio point to irinorecan as a major advance in the field of cytotoxic anticancer
      therapy.

PMID- 9932081
TI  - [Irinotecan: various administration schedules, study of drug combinations, phase
      I experience].
AB  - Irinotecan (CPT11) is a synthetic camptothecin-derived DNA topoisomerase I
      inhibitor. Based on phase I clinical trials, several schedules have been
      recommended for phase I studies including 350 mg/m2 every 3 weeks in Europe, 125
      mg/m2 for 4 weeks every 6 weeks in the USA, and 100 mg/m2 weekly or delayed until
      recovery in case of grade > 2 toxicity in Japan. The principal dose-limiting
      toxicities in those schedules are neutropenia and delayed diarrhea. Early
      treatment with high doses of loperamide has made diarrhea a manageable toxicity
      and allowed dose escalation up to 500 mg/m2. Recently, two very interesting
      schedules have been investigated allowing to increase dose-intensity: every other
      week infusion and protracted infusion. With those schedules, it appears that the
      diarrhea occurred more frequently with the weekly schedule. In addition, authors
      have observed interpatients variations in terms of toxicity and pharmacokinetics.
      Those variations may be related to modifications in the hepatic metabolism of the
      drug that may occur in patients with hepatic dysfunction and/or in patients with
      concomitant medications. The understanding of the individual metabolism of the
      drug would help to determine individual dose adaptation. Based on synergistic
      preclinical interaction with several drugs, combinations of irinotecan with other
      cytotoxic drugs such as thymidylate synthethase inhibitors and platinum salts are
      currently investigated in phase I-II studies.

PMID- 9932082
TI  - [Irinotecan monotherapy in the treatment of colorectal cancers: results of phase
      II trials].
AB  - Irinotecan or CPT11 is a topoisomerase 1 inhibitor. The European and American
      regimens of irinotecan in monotherapy are different: respectively 350 mg/m2 i.v.
      every 3 weeks and 125 mg/m2 i.v. weekly (4 weeks out of 6). In a large phase 2
      programme an important activity has been shown in metastatic colorectal cancer.
      In 5FU resistant colorectal cancer an objective response rate of 13% has been
      shown. This was associated with a long median time of response, a long median
      time to progression and a long median survival. More than 40% of patients had
      also a stabilisation in second line treatment. This interesting activity was the
      basis for the phase 3 studies that have positioned irinotecan as the standard
      treatment in 5FU resistant colorectal cancer. The response rate in first line
      treatment of colorectal cancer varies between 18% and 32%. The main side effects
      are neutropenia and delayed diarrhea.

PMID- 9932083
TI  - [Second-line irinotecan chemotherapy in the treatment of metastatic colorectal
      cancers: phase III trials].
AB  - Treatments of advanced colorectal cancer progressing after a 5FU based
      chemotherapy have not been extensively studied. However, 5FU in continuous
      infusion, L-OHP alone or in combination with 5FU and CPT11 have proved their
      efficacy in terms of tumor growth control and symptomatic effect. Irinotecan only
      has been evaluated prospectively in phase III studies. This paper reports the
      results of the two randomized European studies which have demonstrated the
      efficacy of irinotecan used at the dose of 350 mg/m2 administered over 90 minutes
      every 3 weeks in patients progressing after a 5FU-based chemotherapy. The first
      study compared irinotecan versus best supportive care in a group of 279 patients.
      It demonstrated an overall survival benefit (9.2 versus 6.5 months, p < 0.0001)
      with a one-year survival of 36.2% for patients treated by irinotecan versus
      13.8%. There was also a quality of life benefit, especially for asthenia and pain
      in favor of the irinotecan arm. The second study compared irinotecan to a second
      line infusional 5FU and randomized 260 patients. Irinotecan treated patients
      lived for significantly longer than those on 5FU: median time of survival was
      10.8 months versus 8.5 months (p = 0.035). Survival at 1 year was increased from
      32% in the 5FU arm to 45% in the irinotecan arm. Pain-free survival and symptom
      free survival were better for patients treated by irinotecan and the global
      quality of life score was in favor of irinotecan when assigning null value to
      missing data due to death in both arms. Both treatments were equally well
      tolerated. These two randomized studies have proved the efficacy of irinotecan as
      second line chemotherapy for colorectal cancers progressing under 5FU.
      Combination of irinotecan to 5FU and/or L-OHP have now to be evaluated in this
      situation.

PMID- 9932084
TI  - [Irinotecan in combination for colon cancer].
AB  - As a single agent, irinotecan has demonstrated efficacy in metastatic 5FU
      resistant colorectal metastatic cancer. Chemotherapy with fluorouracil (5FU) plus
      leucovorin remains a standard in the treatment of patients with metastatic
      colorectal cancer. It seemed logical to test the combination of this reference
      treatment and the new agent. The first trials gave rather disappointing results,
      suggesting an inhibition of the metabolism of irinotecan into SN38 when 5FU was
      present in the circulation. More recent studies have given totally different
      results with a very good tolerance and strong efficacy of the combination of
      weekly folinic acid + 5FU and irinotecan or LV5FU2 (the so-called de Gramont
      regimen) and irinotecan. The results were so good that these new schedules are
      currently developed as first line regimen. Another way to combine 5FU, folinic
      acid and irinotecan is to alternate a cycle of 5FU, folinic acid and a cycle of
      irinotecan. Such an alternated schedule has given encouraging results with an
      objective response rate greater than 30% and a long median survival time (more
      than 16 months). It is also very easy to combine irinotecan with other drug which
      have demonstrated activity in the treatment of colorectal cancer. The
      combinations of irinotecan and mitomycin C or oxaliplatin have given very good
      results with high objective response rates and good tolerance. Irinotecan plays
      now an important part in the treatment of metastatic colorectal cancer. This part
      becomes larger due to the results of the combination trials already presented
      which have shown strong efficacy and good tolerance.

PMID- 9932086
TI  - [The other camptothecins: recent advances with camptothecin analogues other than
      irinotecan and topotecan].
AB  - The first part of this review summarizes the clinical developments concerning
      camptothecin, 9-aminocamptothecin, 9-nitrocamptothecin, GG-211 and DX-8951f. The
      second part covers the recent developments of research on CPT analogs: CPTs with
      solubilizing substituents, CPTs with activating substituents, CPTs with dual
      activity, CPT prodrugs and CPTs with stabilized lactones.

PMID- 9932087
TI  - Tubule density of the stratum medium of horse hoof.
AB  - The number of tubules/mm2 (tubule density) of horse hoof horn was quantified in
      samples taken from the left forefeet of 8 randomly selected slaughterhouse horses
      in order to establish the normal tubule density characteristics at the midline
      dead centre (MDC) for the stratum medium of horse hoof. In the past the
      measurement of tubule distribution within the hoof has lacked objectivity. The
      horse hoof tubule density results are compared to a recent objective study
      carried out on pony hoof. A similar 4 zone pattern of tubule density was
      observed, although the precise zonal boundaries and tubule density values
      differed to those found for pony hoof. There were significant differences in
      tubule density between zones. Comparison with pony hoof revealed significant
      tubule density differences in zones 1, 2 and 4; however, there was no significant
      difference in zone 3. The existence of a 4 zoned pattern of tubule density for
      horse hoof, as for pony hoof, has been confirmed.

PMID- 9932085
TI  - [Irinotecan-containing combinations in solid tumors, except colonic carcinomas].
AB  - Irinotecan is a new topoisomerase I inhibitor. It has demonstrated antitumor
      activity in solid tumors, independently of the histologic type, and in squamous
      cervical carcinoma. Its original mechanism of action offers the possibility to
      combine it with other drugs. In vitro and in vivo studies have demonstrated
      synergistic activity between irinotecan, cisplatin and etoposide. This article
      reviews the main published phases I and II studies with irinotecan. The limiting
      toxicity of combination schedules in neutropenia. The best results were obtained
      with the association cisplatin-irinotecan in lung cancer. For the combination
      etoposide-irinotecan the best schedule of administration remains to be
      determined.

PMID- 9932088
TI  - Exploring the possible functions of equine hoof wall tubules.
AB  - Possible functions of equine hoof wall tubules were investigated in this study.
      Hydration tests were conducted on blocks of hoof wall tissue in order to test the
      hypothesis that hollow tubules facilitate the conduction of water vapour
      distally. Although water loss or gain was inhibited through the outer wall
      surface, the increase in surface area provided by medullary spaces was
      ineffective in facilitating hydration through the face with exposed tubule ends.
      Rather, hollow tubules appear to allow for a higher dehydration rate through
      their exposed ends. Analysis of medullary space indicates that the presence of
      these voids does not provide either a significant increase in flexural stiffness,
      or a decrease in thermal conductivity. These findings suggest that nonmechanical
      roles of hoof wall tubules are unlikely and, therefore, the hollow nature of
      tubules may be a reflection of manufacturing constraints in producing keratin
      fibres at steep angles to the coronary border.

PMID- 9932089
TI  - A permeability barrier in the dorsal wall of the equine hoof capsule.
AB  - The permeability barrier in the dorsal wall of the equine hoof capsule was
      studied by means of horseradish peroxidase (HRP) in 0.9 N saline solution as a
      water soluble tracer. Section were treated with 3'3'-diaminobenzidine
      tetrachloride (DAB) and before dissection the quality of the horn of feet from 10
      horses was assessed and given a subjective grade as either good or poor. Blocks
      of tissue from each horse were left in either an oven at 60 degrees C or in water
      for 2 weeks before treatment in HRP, sectioning and DAB solution. Regions
      observed were i) outer surface, ii) outermost layers of the horn, iii) cut edge
      of the outer layer, iv) inner layer of horn, v) cut edge of the inner layer and
      vi) laminae. Horn deemed to be normal horn and of good 'quality' showed very
      slight penetration of HRP 3-5 cell layers deep in the outer layer. The cut edge
      of the outer layer of the wall of the 'normal' horn also showed minimal
      penetration of HRP through the intercellular spaces. The cut edge of the inner
      layers of the wall of normal, good quality horn showed penetration of the tracer
      up to 20 cell layers deep, with HRP in both the intercellular spaces and within
      the cells. In contrast, sections of horn from horses with brittle feet showed
      deep cracks in the outer surface into which the HRP had penetrated. Good quality
      horn showed no change in the position of the permeability barrier after soaking
      in water for 14 days, but the brittle horn showed an increase in permeability to
      HRP. In brittle horn, reaction product was seen deep within the section in the
      intercellular spaces of the intertubular horn only. Placing horn in an oven had
      no effect on the permeability barrier. The permeability barrier of the dorsal
      wall of the equine hoof capsule differs with the layer of the wall. Horn
      considered to be of poor quality had a weaker permeability barrier than horn of
      good quality.

PMID- 9932090
TI  - Fetal development of the white line (Zona alba) of the equine hoof.
AB  - The fetal development of the white line (Zona alba) in the equine hoof is
      described. Its specific structure of lamellar and interlamellar horn, which in
      turn is composed of cap and terminal horn, is formed in the second half of the
      hoof's fetal development. In equine fetuses with a crown-rump length of less than
      550 mm, the hoof capsule lacks a 'characteristic' white line since no borders
      between stratum medium, stratum internum and sole horn are discernible. In the
      hoof of an equine fetus with a crown-rump length of 550 mm, a narrow white line
      has taken shape. Its shallow lamellae are arranged like arcades. Between the horn
      lamellae lie the polyhedral cells of the interlamellar horn. Up until birth, the
      height of the horn lamellae and, therefore, the width of the white line increases
      significantly. In the white line of the hoof of newborn foals, the terminal horn
      contains horn tubules with a characteristic architecture.

PMID- 9932091
TI  - Onychomycosis in white line disease in horses: pathology, mycology and clinical
      features.
AB  - This paper describes onychomycosis in horses and reports the pathological
      findings, associated fungi and incidence of concurrent white line disease. In
      addition to these observations, relevance between post mortem and clinical
      findings of onychomycosis are discussed in 3 necropsied horses. Samples were
      collected from 100 hooves from a total of 51 Thoroughbreds suffering from white
      line disease. Of these, 15 hooves from 13 horses were also complicated with
      severe hoof wall fissure formation. Preparations from the same samples were used
      both for histopathology and for culture to identify the associated fungi.
      Onychomycosis was diagnosed when it could be confirmed histologically. Fungal
      identification was based on morphological characteristics in culture and the
      associated fungi were determined by comparison with culture morphology. As a
      result, 10 samples collected from horses were diagnosed as suffering from
      onychomycosis. Seven of these showed complicating severe inner hoof wall fissures
      and the soil fungus Scedosporium apiospermum or the teleomorph of this fungus,
      i.e., Pseudallescheria boydii, was isolated. The fungus was found to be
      ubiquitous in the fissure cavities, the terminal horn of the white line and the
      terminal horn-like laminae of the metaplastic white line-like tissue. It can be
      concluded that onychomycosis frequently causes white line disease and/or makes it
      worse. Associated with deterioration of the submural condition, the main
      associated fungus for onychomycosis in this series, was Genus Scedosporium and
      the most susceptible region was the terminal horn of the hypertrophied white line
      and/or the terminal horn-like laminae of the metaplastic white line-like tissue.

PMID- 9932092
TI  - Effect of hoof trimming on the occurrence of distal phalangeal palmar process
      fractures in foals.
AB  - This study sought to determine if extensive trimming of the front hooves of foals
      results in a higher incidence of palmar process fractures compared to untrimmed
      foals, and to characterise the clinical course of foals with palmar process
      fractures with physical findings, hoof measurements and radiography. Twenty foals
      age 4-8 weeks of multiple breeds were examined every 2 weeks over a 12 week
      period. Ten foals had both front hooves extensively trimmed every 4 weeks, while
      10 foals remained untrimmed. Palmar process fractures occurred in 4 trimmed and 3
      untrimmed foals. Four foals with fractures had brief lameness (Grades I-II/V) and
      hoof tester sensitivity was found inconsistently with fractures. All foals with
      fractures were sound at the end of the study. Fractures healed based on
      radiographic evaluations in an average of 8.4 weeks. Two of 3 foals with
      fractures developed club-footed conformation. None of the measured hoof
      parameters significantly differed between foals with and without fractures. We
      conclude that extensive trimming of the heels did not appear to affect the
      occurrence of palmar process fractures in this group of foals.

PMID- 9932093
TI  - Effects of season and diet on tensile strength and mineral content of the equine
      hoof wall.
AB  - Studies evaluating nutritional and seasonal influences on hoof strength and
      composition in horses, as well as the scientific justification for feeding
      supplements to improve hoof quality, are lacking. The horseman and veterinarian
      need controlled studies in this area to make informed decisions. This project
      quantified, in 2 trials, relative elasticity, tensile strength, % moisture, and
      mineral composition of hooves of 48 mature Thoroughbred mares maintained on
      different nutritional/management regimens, sampled quarterly over 12 month
      periods. Tensile strength was positively associated with sulphur content. Per
      cent moisture was not significantly associated with tensile strength, relative
      elasticity, or mineral content measures. Results indicated that both seasonal
      trends and nutritional regimes greatly affected hoof wall strength and mineral
      composition.

PMID- 9932094
TI  - Effect of supplementary dietary biotin on hoof growth and hoof growth rate in
      ponies: a controlled trial.
AB  - The effect of dietary biotin supplementation, at a dose rate of 0.12 mg/kg bwt,
      on growth and growth rate of the hooves of 8 match-paired poines was investigated
      in a controlled feeding trial. Treatment animals had a mean hoof growth at the
      midline dead centre of the hoof capsule of 35.34 mm after 5 months of biotin
      supplementation compared to control animals 30.69 mm (P < 0.05). Comparison of
      regression analysis also showed that biotin supplementation produced a
      significantly higher (P < 0.02) growth rate of hoof horn in this trial. Treatment
      animals had a 15% higher growth rate of hoof horn and 15% more hoof growth at the
      midline dead centre, after 5 months of biotin supplementation compared to control
      ponies. No differences were found between feet for growth of horn, but the older
      animals in the trial had significantly lower hoof growth (P < 0.05) than the
      remaining poines.

PMID- 9932095
TI  - Effect of a supplementary dietary evening primrose oil mixture on hoof growth,
      hoof growth rate and hoof lipid fractions in horses: a controlled and blinded
      trial.
AB  - The lipid chemistry of the normal equine hoof, together with the effect of oral
      supplementation with an evening primrose oil mixture (EPOM) on its growth, growth
      rate and lipid content was assessed in a controlled and blinded feeding trial at
      the Defence Animal Centre. Twelve horses were paired as closely as possible
      according to sex, age, weight, height and colour and then one from each pair was
      randomly allocated to treatment or control groups. The treatment group received
      30 ml of oral EPOM/day, otherwise the nutrition and management regimes were the
      same for all horses. No significant differences (P > 0.05) were seen between
      treatment and control groups for hoof horn growth or growth rate. However, there
      was a significant difference (P < 0.05) in hoof horn growth within the treatment
      group only between weeks 4 and 8 after the start of supplementation. The stratum
      medium contained significantly higher amounts of cholesterol ester (P < 0.05),
      triglycerides (P < 0.001) and free fatty acids (P < 0.05) than the periople. The
      periople contained significantly higher levels of free cholesterol and
      phospholipid (P < 0.001) than the stratum medium of the hoof wall. There were no
      significant differences (P > 0.05) between treatment and control groups for any
      of the lipid fractions measured for the stratum medium from the clippings of the
      hoof wall. However, there were differences in perioplic lipid analysis with
      significant increases (P < 0.05) in cholesterol esters and partial glycerides and
      a significant reduction (P < 0.001) in free cholesterol in the treatment group
      following supplementation.

PMID- 9932096
TI  - Cytokeratins of the equine hoof wall, chestnut and skin: bio- and immunohisto
      chemistry.
AB  - The equine skin and its appendages (chestnut, hoof capsule, ergot, sebaceous
      glands, sweat glands and hair) consist mainly of keratinocytes. The intermediate
      filament cytoskeleton of these cells in involved in specialised functions, such
      as mechanical co-ordination of the cytoskeleton of the cell or tissue. In this
      study, 7 monoclonal antibodies, one polyclonal antibody and immunoblot analysis
      were used to characterise cytokeratins (separated by 1- and 2-dimensional gel
      electrophoresis) from the hoof wall and chestnut. The tissue distribution of
      these cytokeratins was studied by immunohistochemical staining of sections from
      the skin, chestnut, periople, matrix of the stratum medium of the hoof wall, and
      the stratum internum of the hoof wall. The results of analysis revealed a
      difference in the content of cytokeratins between: 1) cell layers within the same
      tissue, 2) skin and more proliferative epidermal tissues, i.e., chestnut and
      periople, 3) tissues containing a stratum granulosum (skin, chestnut and
      periople) and tissues without stratum granulosum (stratum medium and internum of
      the hoof wall), 4) stratum medium and stratum internum of the hoof wall and 5)
      stratum internum at the most proximal level and at the mid level of the hoof
      wall.

PMID- 9932097
TI  - Effect of rider and riding style on deformation of the front hoof wall in
      warmblood horses.
AB  - A rider modifies the weight distribution and dynamic balance of the horse. But
      what effect does a rider have on the mechanical behaviour of the hoof during each
      stance phase? Does riding style have any effect on this behaviour? We attempted
      to answer these questions using strains recorded from 5 rosette strain gauges
      glued to the surface of the front hooves of 4 Warmblood horses. Comparisons were
      made between strains with and without a rider, and when the rider was sitting,
      rising at a trot, or in a forward seated position. The change in strains from
      trot to lead or nonlead at a canter, and the effect of turning were also studied.
      Changing lead at a canter had as least as much effect on strain magnitudes as did
      turning; strains were up to 43% higher for the nonlead foot, but with little
      redistribution. Perhaps surprisingly, strains were significantly lower on the
      quarters by up to 30% with a rider than without, with a 10% increase or decrease
      at the toe, depending on the individual. Riding style changed strain magnitudes
      by up to 20% and also caused strain redistribution: strains were higher medially
      for sitting, and laterally for forward seat, with strains for a rising trot being
      more evenly distributed and intermediate in magnitude. Studying the range of, and
      causes of variation in hoof wall strain gives baseline data aimed, in the long
      term, at providing a biomechanical definition of hoof balance.

PMID- 9932098
TI  - Variation in surface strain on the equine hoof wall at the midstep with shoeing,
      gait, substrate, direction of travel, and hoof shape.
AB  - Objectives were to examine the deformation of the healthy equine front hoof
      during locomotion, by recording strains on its outer surface, and to test whether
      its mechanical behaviour is significantly altered under different locomotory
      conditions and variation in hoof shape. Strains were recorded in vivo from 5
      rosette gauges around the circumference of the right forehooves of 12 horses. The
      magnitudes and orientations of principal strains at the midstep were compared
      statistically for different conditions of shoeing (shod vs. unshod), gait (walk
      vs. trot), substrate (treadmill vs. ground), and direction of travel (straight,
      right turn, left turn). Principal strains were regressed on 4 variables
      describing hoof shape-toe length, toe angle, and medial and lateral wall angle-
      to describe their contribution to variations in strain and hoof deformation.
      Shoeing did not essentially change the magnitudes of the larger, compressive
      principal strain, but caused some strain reorientation. Shoes decreased the
      variation in strains indicating that they tend to stabilise the deformation of
      the hoof. Strain magnitudes were significantly greater at trot than walk, but
      there was little change in orientation indicating that the general pattern of
      deformation of the hoof is constant between these 2 gaits. Strain patterns showed
      small but significant differences between locomotion on the treadmill and on
      ground, with the differences being more apparent at the toe than at the sides of
      the hoof. When turning, the quarter on the inside of the turn experienced 40%
      more strain than during straightline motion, while strain was similarly reduced
      on the opposite quarter. Strain magnitudes increase with toe length and toe
      angle, but were inversely proportional to medial and lateral angles. The change
      with toe length correlated with the range of body size of the animals in the
      sample. The change with toe angle was contrary to that found in in vitro tests.
      The change with medial and lateral angles indicated that hooves with more upright
      quarters are stiffer and possibly provide less impact absorption.

PMID- 9932099
TI  - In vitro attenuation of impact shock in equine digits.
AB  - This study was designed to test the impact characteristics of the equine digit in
      vitro with the objective of providing a better understanding of the role of the
      digital structures in the attenuation of impact shock. Uni-axial accelerometers
      were mounted on cadaver digits on the distolateral hoof wall, the proximolateral
      hoof wall, the dorsal surface of the second phalanx, and the mid-lateral first
      phalanx. The hoof-mounted accelerometers were aligned with the hoof tubules while
      the bone-mounted accelerometers were oriented along the longitudinal axis of the
      bone. Each digit was mounted in a test apparatus designed to simulate impact of
      the hoof with the ground during locomotion. The digits were subjected to 3 impact
      trials against a barrier at each of 3 vertical impact velocities that simulated a
      forward trotting velocity in the range of 2.67 to 4.46 m/s. The impact
      deceleration tended to increase with impact velocity. Attenuation of the impact
      shock by the digital tissues resulted in a reduction in impact decleration in the
      more proximal measuring locations. The interphalangeal joints appeared to play a
      larger role in amplitude attenuation than the hoof wall or the soft tissue
      structures within the hoof wall. The signal frequency data showed that the soft
      tissues within the hoof acted as a 'lowpass' filter, attenuating the higher
      deceleration frequencies. The hoof wall and the interphalangeal joints showed
      little frequency attenuation.

PMID- 9932100
TI  - Finite element analysis of static loading in donkey hoof wall.
AB  - A finite element model of donkey hoof wall was constructed from measurements
      taken directly from the hoof capsule of the left forefoot. The model was created
      with a 2 mm mesh and consisted of 11,608 nodes. A linear elastic analysis was
      conducted assuming isotropic material properties in response to a 375 newton (N)
      load, to simulate static loading. The load was applied to the wall via 400
      laminae in order to simulate the way in which the pedal bone is suspended within
      the donkey hoof capsule. Displacement, stress concentration, principal strain,
      and force distribution across the hoof wall were evaluated. The hoof wall model
      revealed loading responses that were in broad agreement with previously reported
      in vivo and modelled observations of the equid hoof. Finite element analysis
      offers the potential to model hoof wall function at the macroscopic and
      microscopic level. In this way, it could help to develop further our
      understanding of the functional relationship between the structural organisation
      and material properties of the hoof wall.

PMID- 9932101
TI  - Digital perfusion, evaluated scintigraphically, and hoof wall growth in horses
      with chronic laminitis treated with egg bar-heart bar shoeing and coronary
      grooving.
AB  - Nuclear scintigraphy was used to assess digital perfusion before and after
      treatment in 10 horses with clinical and radiographic evidence of chronic
      laminitis. Horses were evaluated for lameness, degree of distal phalanx rotation,
      and heel-toe hoof wall growth ratio, and randomly divided into two treatment
      groups. Group 1 horses received only egg bar-heart bar shoeing; Group 2 underwent
      egg bar-heart bar shoeing and coronary grooving. Horses were re-evaluated for
      digital perfusion, lameness, degree of distal phalanx rotation, and hoof wall
      growth at 6 week intervals over the 18 week follow-up period. Prior to treatment,
      relative scintigraphic activity at the dorsal laminar area was decreased and
      relative scintigraphic activity at the toe and adjacent solar area was increased.
      Egg bar-heart bar shoeing was associated with significantly increased dorsal
      laminar scintigraphic activity and significantly decreased solar scintigraphic
      activity over the 18 week period. Coronary grooving, in combination with egg bar
      heart bar shoeing, resulted in a significantly lower heel-toe hoof wall growth
      ratio but did not enhance digital perfusion. Seven of 10 (70%) horses were
      responsive to treatment, defined as an improvement in lameness by at least one
      grade. Horses that were refractory to treatment had significantly lower dorsal
      laminar scintigraphic activity and higher palmar coronary scintigraphic activity
      prior to treatment than horses that responded to treatment. Our results are the
      first to demonstrate that egg bar-heart bar shoeing is associated with improved
      dorsal laminar perfusion, and support the use of this technique. In addition, we
      found that pre-treatment nuclear scintigraphy was predictive of clinical outcome
      in horses with chronic laminitis treated with corrective shoeing.

PMID- 9932102
TI  - Batimastat (BB-94) inhibits matrix metalloproteinases of equine laminitis.
AB  - A method for culturing explants of lamellar hoof was developed to investigate the
      process of lamellar separation that occurs in laminitis. Explants, consisting of
      hoof wall, dermal and epidermal lamellae and the adjacent sub-lamellar connective
      tissue remained intact when cultured in tissue culture medium for 2 days.
      However, when cultured in the presence of the matrix metalloproteinase (MMP)
      activator aminophenylmercuric acetate (APMA), the lamellae separated when tension
      was applied by pulling the hoof wall in an opposite direction to the connective
      tissue. The separation occurred between the epidermal basal cells and the
      basement membrane therefore mimicking the lesion of laminitis. Electrophoresis of
      culture medium from control hoof explants into gradient polyacrylamide gels co
      polymerised with gelatin revealed that the explants had produced 2 gelatinases of
      molecular weight 92 and 72 kDa corresponding to EqMMP-9 and EqMMP-2 respectively.
      Minor bands of lower molecular weight were the active forms of these enzymes. The
      zymograms of culture medium from APMA treated explants revealed an increase in
      the amount of active MMPs. Equine polymorphs cultured for 2 days produced only
      EqMMP-9. Lamellar explant medium from horses with acute laminitis contained
      increased amounts of zymogen and active EqMMP-2 and EqMMP-9 particularly in
      explants from the fore hooves. Zymography of homogenates of normal lamellar hoof
      tissue revealed only EqMMP-2 and a minor active band. However, homogenates of
      lamellar tissue from horses with laminitis showed that EqMMP-9 was present as
      well as increased EqMMP-2 in both zymogen and active forms. Addition of the MMP
      inhibitor batimastat (BB-94) to the culture medium of APMA treated explants
      prevented lamellar separation. BB-94 incubated with polyacrylamide strips
      containing the MMPs from laminitis affected lamellar explants inhibited enzymatic
      activity at a concentration of 1 mmol/l. It is concluded that activation of MMPs
      may be responsible for the lamellar separation seen in laminitis and that MMP
      inhibitors may be useful clinically for preventing this process.

PMID- 9932103
TI  - Equine laminitis: its development coincides with increased sublamellar blood
      flow.
AB  - The effect of alimentary carbohydrate overload on hoof temperature was
      investigated to determine the state of the sublamellar vasculature preceding the
      onset of equine laminitis. Hoof, core and ambient temperatures and heart rate
      were logged continuously in 21 mature Standardbred horses kept in an
      environmental chamber set at 10 degrees C. Recording hoof temperature was a
      successful, noninvasive, method to measure indirectly, shifts in digital blood
      flow against a background of cold induced, physiological, vasoconstriction. High
      hoof temperatures were assumed to indicate digital vasodilation and low hoof
      temperatures digital vasoconstriction. Seven horses were either untreated or sham
      treated controls. A slurry of ground wheat flour (17.5 g/kg) was administered via
      nasogastric tube to 13 horses all of which were humanely killed 48 h later.
      Histological sections of the lamellar tissues were examined for evidence of
      laminitis. Analysis of mean hoof temperature graphs showed that horses judged
      laminitis positive had experienced a period of prolonged digital vasodilation 16
      40 h after carbohydrate overload. Laminitis negative horses experienced no such
      period of vasodilation and never had hoof temperatures significantly (except
      once, at 28 h) above that of controls. The only parameter which significantly
      differentiated the laminitis positive from laminitis negative horses, between 12
      and 32 h after carbohydrate overload, was foot temperature, which was
      significantly higher in laminitis positive horses (P < 0.05). Therefore, a period
      of sublamellar vasodilation, 12 to 40 h after alimentary carbohydrate overload
      precedes the onset of laminitis. If the digital circulation sustains
      vasoconstriction during this period then laminitis does not occur. We propose
      that the period of increased digital blood flow in laminitis positive horses,
      concomitant with the severe metabolic crisis brought on by the alimentary
      carbohydrate overload, may expose the lamellar tissues to a concentration of
      blood borne factors sufficient to trigger lamellar separation.

PMID- 9932104
TI  - Decreased glucose metabolism causes separation of hoof lamellae in vitro: a
      trigger for laminitis?
AB  - Explants of horses' hooves remained intact for up to 8 days when incubated in
      Dulbecco's modified Eagle medium (D-MEM) containing 25 mmol/l glucose but
      separated within 36 h when incubated in saline. The separation occurred between
      the basal epidermal cells and their basement membrane which is characteristic of
      the hoof separation that occurs in laminitis. Separation of hoof explants was
      prevented by addition of glucose to saline and was induced by adding 2
      deoxyglucose or aminophenylmercuric acetate to D-MEM. Glucose consumption by the
      hoof explants was inhibited by 2-deoxyglucose and aminophenylmercuric acetate.
      The explants consumed relatively large amounts of glucose during the first 2 days
      of incubation and then little over the next 6 days. Despite the reduced glucose
      consumption, the hoof explants did not separate over 8 days of incubation. The
      results indicated that the integrity of the hoof explants was initially dependent
      on consumption of glucose and provide a possible explanation for the development
      of laminitis caused by conditions such as carbohydrate overload, acute
      inflammatory conditions, corticosteroid therapy and hyperlipidaemia. It would be
      expected that these conditions would induce a major hormonally-mediated metabolic
      shift away from glucose consumption by many peripheral tissues. It is suggested,
      therefore, that if the metabolic change occurred faster than the hoof tissue
      could adapt to an alternative energy substrate, then hoof separation and
      laminitis would occur.

PMID- 9932105
TI  - Equine laminitis basement membrane pathology: loss of type IV collagen, type VII
      collagen and laminin immunostaining.
AB  - Disintegration of the basement membrane (BM) of the equine hoof lamellae and
      failure of the BM to remain attached to the basal cells of the secondary
      epidermal lamellae (SEL) is one of the earliest pathological events to occur in
      acute laminitis. Changes in the lamellar basement membrane were investigated by
      immunolabelling the key structural components of the BM, type IV collagen, type
      VII collagen and laminin in the lamellar BM of horses 48 h after the induction of
      laminitis. Lamellar tissues were harvested from 2 normal horses and 2 horses with
      acute laminitis. Immunostaining with antibody raised against human epitopes for
      type IV collagen, type VII collagen and laminin successfully stained the basement
      membranes of horse hoof lamellar tissues. Vascular tissue did not immunostain
      with type VII collagen antibody. Normal BM stained as a fine dark brown line and
      the lamellar BM was adhered to the basal cells of the SELs with no evidence of
      lamellar separation. At least 2 changes to the lamellar BM occurred in acute
      laminitis: loss of attachment of lamellar epidermal basal cells to their
      underlying BM and disintegration of the lamellar BM. In some sections from feet
      affected by acute laminitis, there was widespread separation of the SELs from
      their BM without loss of BM immunostaining and in others there was extensive loss
      of BM immunostaining. In lesions characterised by lamellar separation, the
      epidermal basal cells at the tips of the primary epidermal lamellae appeared to
      have slipped away from their BM and were an amorphous clump of epidermal cells
      devoid of immunostained BM. The BM from which they had separated remained in its
      original position in the dermis and was clearly outlined by all 3 antibodies. In
      other areas, however, virtually all the BM immunoreactivity at the PEL tips was
      absent. Only the occasional distorted SEL tip and fragments of BM retained
      sufficient immunostaining to allow anatomical identification. Numerous
      polymorphonuclear leucocytes (PMNs) invariably surrounded the tips of lamellae
      showing large scale loss of immunoreactivity and many PMNs had penetrated the
      lamellar BM and were within the epidermal compartments. PMNs were less frequent
      in the midlamellar region. Immunostaining of the BM of many SELs was absent in
      the midlamellar region. In some lamellae loss of BM immunostaining had occurred
      only at the bases of the SELs and fragments of immunostained BM were present in
      the zones of lysed BM suggesting that BM lysis was incomplete at the time of
      tissue fixation. In other lamellae, lysis of the BM was complete; there was no
      immunostained BM between SELs and the bulk of the epidermal cells of each PEL
      were an amorphous column of cells on either side of the central keratinised axis
      of the PEL. The lamellar BM which remained appeared as immunostained strands of
      unattached BM along the edges of the PDLs. Activation of BM degrading
      metalloproteinases (MMPs) occurs in acute laminitis and it seems likely that
      uncontrolled MMP activity is responsible for the loss and disorganisation of
      lamellar BM demonstrated in this study.

PMID- 9932106
TI  - The Hauptman-Woodward Medical Research Institute, Inc.

PMID- 9932107
TI  - Requirements for enhanced transgene expression by untranslated sequences from the
      human cytomegalovirus immediate-early gene.
AB  - BACKGROUND: The cytomegalovirus immediate early (CMV IE) promoter has been widely
      used for heterologous expression. Further enhancements of gene expression from
      this potent promoter may allow for the development of improved gene transfer
      strategies. We aimed to determine whether inclusion of the first exon (5'
      untranslated) and first intron of the CMV IE gene would increase heterologous
      transgene expression in primary target cells and to determine the sequences
      required for any observed increases. MATERIALS AND METHODS: Comparisons of
      reporter gene expression were made following transient transfection of vascular
      smooth muscle cells (VSMCs) with plasmids containing the first exon and intron
      from the CMV IE gene or deletional mutations. Comparisons were also made using a
      heterologous promoter (RSV). RESULTS: Gene expression from the CMV IE promoter
      was increased 5.7-fold in VSMC with the inclusion of the first exon and intron.
      Similar increases were seen with other target cells and from the heterologous RSV
      promoter. This increase was associated with an increase in steady-state mRNA.
      Deletion analyses demonstrated that the enhancement was dependent on the presence
      of the 5' portion of the first exon while deletion of large segments within the
      intron was associated with similar levels of expression compared with the
      parental plasmid. CONCLUSIONS: Inclusion of the first exon and intron from the
      CMV IE gene increases expression from the CMV IE promoter. This enhancement is
      seen with the heterologous RSV promoter and is associated with an increase in
      steady-state mRNA. Deletion analyses suggest that this enhancement is associated
      with inclusion of sequences within the 5' portion of the first exon and inclusion
      of an intron.

PMID- 9932108
TI  - Involvement of macrophage migration inhibitory factor (MIF) in the mechanism of
      tumor cell growth.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) was recently
      rediscovered as a cytokine, pituitary hormone, and glucocorticoid-induced
      immunomodulator. MIF is constitutively expressed in various cells and enhances
      production of inflammatory cytokines such as tumor necrosis factor-alpha,
      interleukin-1, and interferon gamma. Recently, it was reported that MIF mRNA was
      overexpressed in prostatic tumors, which suggests that MIF is a protein involved
      in tumor cell growth beyond inflammatory and immune responses. MATERIALS AND
      METHODS: We examined the expression of MIF in the murine colon carcinoma cell
      line colon 26 by Western and Northern blot analyses and immunohistochemistry.
      Next, we investigated the effects of transforming growth factor (TGF) beta, basic
      fibroblast growth factor (b-FGF), and platelet-derived growth factor (PDGF) on
      the expression of MIF mRNA. Furthermore, we examined whether MIF is involved in
      tumor cell proliferation, using an MIF anti-sense plasmid transfection technique.
      RESULTS: We demonstrated that MIF protein and its mRNA were highly expressed in
      colon 26 cells, using Western and Northern blot analyses, respectively. By
      immunohistochemical analysis, we found that MIF was localized largely in the
      cytoplasm of the tumor cells. In response to TGF-beta, b-FGF, and PDGF, MIF mRNA
      expression was significantly up-regulated. Following this, we transfected the
      cells with an anti-sense MIF plasmid, which revealed that this treatment induced
      significant suppression of cell proliferation. CONCLUSION: Although MIF plays
      multifunctional roles in a broad spectrum of pathophysiological states, little
      has been done to investigate the role of this protein in association with tumor
      growth. The current results suggest the possibility that MIF induces tumor cell
      growth in concert with other growth factors, which encouraged us to investigate a
      novel approach for tumor therapy using an anti-MIF antibody and an MIF anti-sense
      plasmid transfection technique.

PMID- 9932109
TI  - Post-transcriptional contribution of a cAMP-dependent pathway to the formation of
      alpha- and beta/gamma-secretases-derived products of beta APP maturation in human
      cells expressing wild-type and Swedish mutated beta APP.
AB  - BACKGROUND: The physiopathological maturation of the beta-amyloid precursor
      protein can be modulated by effectors targeting a protein kinase C-dependent
      pathway. These agents increase the recovery of APP alpha, the physiological alpha
      secretase-derived product of beta APP processing, and concomittantly lower the
      production of the pathogenic beta/gamma-secretase-derived A beta fragment.
      METHODS: We set up stably transfected HEK293 cells expressing wild-type or
      Swedish mutated beta APP. By combined metabolic labeling and/or
      immunoprecipitation procedures, we assessed the effect of various cAMP effectors
      on the production of the beta APP maturation products A beta 40, A beta 42, APP
      alpha, and its C-terminal counterpart. RESULTS: We show here that the cAMP
      dependent protein kinase (PKA) effectors, dibutyryl-cAMP (dBut-cAMP) and
      forskolin, but not the inactive analog dideoxyforskolin, enhance the secretion of
      APP alpha and the intracellular production of its C-terminal counterpart (p10) in
      stably transfected HEK293 cells. The above agonists also drastically increase
      both A beta 40 and A beta 42 secretions and intracellular A beta recovery. The
      same influence was observed with HEK293 cells overexpressing the Swedish mutated
      beta APP. We attempted to delineate the relative contribution of transcriptional
      and post-transcriptional events in the cAMP-mediated response. We show here that
      the dBut-cAMP and forskolin-induced increase of APP alpha and A beta s secretions
      is not prevented by the transcription inhibitor actinomycin D. CONCLUSION: Our
      data suggest a major contribution of post-transcriptional events in the cAMP
      dependent effect on beta APP maturation. It appears likely that cAMP triggers the
      PKA-dependent phosphorylation of a protein involved in beta APP maturation and
      occurring upstream to alpha- and beta/gamma-secretase cleavages.

PMID- 9932111
TI  - Intrathecally, Caine may dis-Able. Reflections on lidocaine for spinal
      anesthesia.
AB  - This paper was presented in September 1997 during a Round Table Discussion on
      lidocaine toxicity, held at the Nobel Forum, Karolinska Institute, Stockholm,
      Sweden. The occasion was in honor of Professor emeritus Torsten Gordh, who in
      August 1997 celebrated his 90th birthday. Torsten Gordh, also present at the
      Round Table Discussion, was the first anesthesiologist who used lidocaine
      clinically. Today, when some clinical problems with the intrathecal use of
      lidocaine are discussed, we are indeed fortunate to have Torsten Gordh still most
      vital and active in our midst.

PMID- 9932112
TI  - Xylocain (lidocaine, lignocaine), its discovery and Gordh's contribution to its
      clinical use.
AB  - Hans v. Euler, while investigating how genes and enzymes were chemically related
      in some chlorofylldefective mutants of barley, isolated gramine, an indole.
      Erdtman synthetized isogramine and found it to have weak anesthetic properties.
      He then together with Lofgren synthetized other amino-amides, but no one of them
      could compete with the existing local anesthetics of the ester-type, derivatives
      of para-aminobenzoic acid, e.g. procaine. Later Lofgren and Lundqvist followed up
      these studies and found an amid compound lidocaine (2-dimethylaminoacet-2, 6
      xylidide). Lidocaine represented such a significant advance over procaine in
      clinical tests preformed by T. Gordh that it was introduced for clinical use. It
      has now during a half century been the standard local anesthetic drug. All local
      anesthetics are neurotoxic in high enough doses. Xylocain, however, has had an
      excellent record of safety. Only during the last years have there been reports on
      possible toxic irritation and damage by Xylocain used for spinal anesthesia. The
      aetiology is still not clear In this connection two early observations by Gordh
      and his coworkers are discussed.

PMID- 9932110
TI  - Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter
      polymorphism related to joint damage in rheumatoid arthritis.
AB  - BACKGROUND: Functional heterogeneity in the tumor necrosis factor alpha (TNF
      alpha) gene may be responsible for the TNF-alpha response in infectious and
      autoimmune diseases. Recently, the TNF-238 promoter polymorphism was observed as
      being associated with a more destructive disease in rheumatoid arthritis (RA). To
      determine the relation between TNF-238 and disease progression, the extent of
      joint destruction in a cohort of 101 RA patients followed for 12 years was
      analyzed. Furthermore, we have attempted to link this polymorphism to TNF-alpha
      gene transcription in monocytes and lymphocytes in vitro. PATIENTS, MATERIALS,
      AND METHODS: The extent of joint destruction determined on X-rays of hands and
      feet assessed after 0, 3, 6, and 12 years was compared with TNF-238 genotypes.
      Functional consequences of TNF-alpha gene polymorphisms using reporter gene
      constructs were analyzed in cells of the monocyte and lymphocyte lineage by means
      of transient transfection systems. RESULTS: The rate of joint damage in -238GA
      patients was lower than that in the -238GG patients, independent of HLA-DR4.
      Damage after 12 years was 76 +/- 30 for the -238GA versus 126 +/- 13 for the 
      238GG patients as determined by the van der Heijde's modification of Sharp's
      method. Furthermore, TNF-238A was found to be in linkage disequilibrium with an
      additional polymorphism at position -376. Functional assays revealed no
      significant differences in the level of inducible reporter gene expression
      between the TNF-238/-376 promoter constructs in the cell types tested.
      CONCLUSION: In a prospective study, we show that the TNF-238GG genotype
      contributes to progression of joint destruction in RA, independent of the
      presence of HLA-DR4. However, in vitro transfection assays indicate that TNF-238A
      by itself or in combination with TNF-376A is not likely to be of direct
      functional relevance for transcriptional activation. Therefore, these
      polymorphisms may serve as markers for additional polymorphisms in the TNF/LT
      locus or neighboring genes that may influence disease severity.

PMID- 9932113
TI  - Postural changes in respiratory function.
AB  - Changes in body position alters the functional residual capacity (FRC). Most
      anesthetics reduce FRC in the recumbent but not sitting position. Inspired gas
      distribution in anesthesia-paralyzed subjects whose lungs are mechanically
      ventilated, is different from that in the awake state in all but the prone
      position. The function of the diaphragm is altered by postural changes. The
      pattern of motion of the diaphragm is different during mechanical ventilation
      than during spontaneous breathing. Also the end-expiratory shape is affected by
      induction of anesthesia, but this shape change contributes little to the
      reduction of FRC. The distribution of pulmonary blood flow is determined not only
      by gravity, but also by an intrinsic non-gravity dependent factor. These two
      factors can be additive in some positions but opposing in others.

PMID- 9932115
TI  - Spinal anaesthesia for caesarean delivery.

PMID- 9932114
TI  - Whitacre or Quincke needles--does it really matter.
AB  - BACKGROUND: Postdural puncture headache (PDPH) and backache are well known
      complications of spinal anaesthesia. The incidence of PDPH may be significant in
      young people (< 50 years). The present study was undertaken in order to compare
      the utility and complication rate of the Whitacre and Ouincke spinal needles.
      METHODS: During three years all patients who could comply, and who were to
      undergo spinal anaesthesia at the Department were asked to join this quality
      control study. Each one received a questionnaire including questions about
      discomfort and other possible side effects attributed to spinal anaesthesia. In
      each case, an extended anaesthetic record was filled out by the
      anaesthesiologist. About 50 anaesthesiologists at different educational levels
      were involved. RESULTS: The study includes 2598 cases, of which questionnaires
      were returned by 66%. Needles of the 25 G gauge size were used in over 90% of the
      cases. Multiple skin punctures were required more frequently in the Quincke than
      in the Whitacre group (P < 0.01). The number of insufficient blocks was also
      higher in the Quincke group (P < 0.01). There was a higher incidence of backache
      in the Quincke group (P < 0.05). In patients under 50 years, PDPH was more
      frequent following use of the Quincke needle (P < 0.05), whereas no difference
      between the needles in this regard was found among those over 50 years (P >
      0.05). CONCLUSIONS: For routine clinical use the Whitacre needle appears to be
      associated with better performance and increased reliability. In younger patients
      the Whitacre needle have the additional advantage of decreasing the risk of
      postdural puncture headache.

PMID- 9932116
TI  - Pain analysis in prediction of treatment outcome.

PMID- 9932118
TI  - Trends and targets for treatment of pain, a pharmaceutical industry perspective.

PMID- 9932117
TI  - The role of nitric oxide in neuropathic pain and neurodegeneration.
AB  - To Torsten Gordh senior: I was asked to participate in this celebration day
      arranged because of your 90 years birthday, and I am really glad to do so, in
      order to honor my father. In my lecture I will connect to Torsten Gordh senior's
      deep and well known interest for the spinal cord and anaesthesia/analgesia, and
      today discuss the role of nitric oxide (NO) in the spinal cord, and its
      importance for neuropathic pain and neurodegeneration.

PMID- 9932119
TI  - How anaesthesiology came to Sweden.

PMID- 9932120
TI  - Clinical outcome of supratentorial astrocytoma WHO grade II.
AB  - OBJECTIVE: There are divergent opinions about the prognostic value of the extent
      of surgery and of different histological subtypes in supratentorial astrocytomas
      WHO grade II. METHODS: We reviewed 75 consecutive patients (36 females, 39 males)
      with supratentorial astrocytomas WHO grade II (59 primary and 16 recurrent
      tumours) operated on between 1991 and 1995. RESULTS: Gross total resection could
      be achieved in 40 astrocytomas, subtotal resection (including biopsy) was
      performed in 35 cases. Histological assessment confirmed 60 fibrillary, 6
      gemistocytic, 9 oligo-astrocytic and no protoplasmic astrocytomas. There were no
      postoperative deaths. Early outcome 6 to 12 weeks after surgery according to the
      Glasgow Outcome Scale was good in 46 patients, 24 patients had moderate, and 5
      had severe neurological deficits. Survival rates 1, 2, 3, and 4 years following
      surgery were 100%, 96%, 96%, 96% for patients who underwent gross total tumour
      resection and 86%, 77%, 77%, 64% for patients with subtotal tumour resection. The
      cumulative recurrence or progression rates after 4 years were 26% after gross
      total resection and 80% after subtotal resection, and this result is
      statistically significant. Recurrences after gross total resection or
      progressions after subtotal resection occurred more often in gemistocytic
      astrocytomas (40% and 100%, respectively) than in other subtypes.
      Dedifferentiation to a more malignant tumour seems to be more prominent in the
      gemistocytic subtype. CONCLUSION: Gross total resection should be the leading
      therapeutic option for patients with astrocytomas WHO grade II. For the
      gemistocytic subtype further studies will have to prove whether additional
      radiotherapy is of any benefit.

PMID- 9932121
TI  - Preoperative functional magnetic resonance imaging (fMRI) of the motor system in
      patients with tumours in the parietal lobe.
AB  - Intracranial lesions may compromise structures critical for motor performance,
      and mapping of the cortex, especially of the motor hand area, is important to
      reduce postoperative morbidity. We investigated nine patients with parietal lobe
      tumours and used functional MRI sensitized to changes in blood oxygenation to
      define the different motor areas, especially the primary sensorimotor cortex, in
      relation to the localization of the tumour. Activation was determined by pixel-by
      pixel correlation of the signal intensity time course with a reference waveform
      equivalent to the stimulus protocol. All subjects showed significant activation
      of the primary sensorimotor cortex while performing a finger opposition task with
      the affected and unaffected side. In five patients the finger opposition task
      additionally activated the ipsilateral sensorimotor cortex and the supplementary
      motor area (SMA). Extension and flexion of the foot, additionally performed in
      two patients, also activated the sensorimotor cortex, in one case within the
      perifocal oedema of the tumour. Tumour localization near the central sulcus
      induced displacement of the sensorimotor cortex as compared to the unaffected
      side in all patients with a relevant mass effect. The results of our study
      demonstrate that functional MRI at 1.5 T with a clinically used tomograph can
      reproducibly localize critical brain regions in patients with intracranial
      lesions.

PMID- 9932122
TI  - Suprasellar meningiomas--neurological and visual outcome at long-term follow-up
      in a homogeneous series of patients treated microsurgically.
AB  - Most of the previously published surgical series of suprasellar meningiomas have
      two disadvantages: (1) patients involved were treated within a relatively long
      time period, making analysis more difficult, (2) radiographic long term follow-up
      examinations with either CT- or MRI-scans were not performed. Both disadvantages
      were overcome in our retrospective clinical study, consisting of 50 consecutive
      patients with suprasellar meningiomas treated between 1982 and 1991.
      Radiological, ophthalmological, and neurological investigations were performed
      preoperatively, postoperatively and at long term follow-up (mean: 5.7 years). A
      radiologically confirmed radical tumour removal could be achieved in 84% of
      patients. Both, the peri-operative mortality (2%) and serious operative morbidity
      (6%) were low. However, 12% of patients developed late onset epilepsy. At long
      term follow-up, visual function was improved in 67%, unchanged in 9% and worsened
      in 24%. In more than 50% of patients the vision showed recovery over a longer
      time period than the first 10 days after operation. Radiographic control
      examinations revealed tumour recurrences in 2 patients (both asymptomatic) and
      progress of residual tumour in 5 patients (2 symptomatic, 3 asymptomatic). Since
      introduction of modern neurosurgery, a clear improvement in the surgical
      treatment of suprasellar meningiomas can be observed. However, the still long
      delay in diagnosing these tumours correctly prevents a further improvement of the
      ophthalmological results at long-term follow-up. Due to a relatively high rate of
      late onset epilepsy, anticonvulsive prophylaxis for 6 months seems to be
      justified. Regarding present preoperative diagnostic measures, ia-DSA seems only
      be indicated in patients with CT/MRI-scans, suspicious for tumourous narrowing or
      invasion of major cerebral arteries. In addition, we recommend radiographic
      control examinations at regular time intervals to confirm radical tumour removal
      and to detect the "ideal" point of time for renewed treatment.

PMID- 9932123
TI  - Unco-parahippocampectomy for direct surgical treatment of downward transtentorial
      herniation.
AB  - Downward transtentorial herniation is a major cause of death and disability
      caused by acute supratentorial mass lesions. Thirteen patients, 7 men and 6 women
      aged from 23 to 75 years old, with progressive transtentorial herniation caused
      by cerebral contusion with acute subdural haematoma, acute brain swelling after
      aneurysmal subarachnoid haemorrhage, or massive cerebral infarction were treated
      by direct surgery using selective removal of the uncus and parahippocampal gyrus
      (unco-parahippocampectomy). All patients showed progressive deterioration of
      transtentorial herniation (late third nerve stage or midbrain stage) with
      unilateral pupillary dilation and absent light reflex. Preoperative Glasgow Coma
      Scale scores ranged from 4 to 8. Unco-parahippocampectomy was performed via the
      middle temporal gyrus under the operating microscope. The oculomotor nerve,
      posterior cerebral artery, and midbrain were directly decompressed. Incision of
      the arachnoid membrane in the tentorial incisura allowed free communication of
      the cerebrospinal fluid between the supra- and finfra-cranial fossae to reduce
      the pressure gradient. Two of the 13 patients died (15%). Two of the 11 survivors
      (18%) were functionally independent and 1 (9%) required minimal assistance but
      was independent at home. This series suggests the lifesaving nature of unco
      parahippocampectomy in patients with deteriorating clinical condition because of
      transtentorial herniation.

PMID- 9932124
TI  - Macrophage tissue infiltration, clinical symptoms, and signs in patients with
      lumbar disc herniation. A clinicopathological study on 179 patients.
AB  - It is postulated that in addition to nerve-root compression, an inflammatory
      stimulus of the herniated lumbar disc is responsible for sciatic pain and
      radiculopathy. The clinical relevance of the histologically described
      inflammatory infiltrates is, however, not clearly defined [8, 22]. It was the aim
      of this study to assess the clinical relevance of inflammatory cells in herniated
      lumbar disc specimens. The presence of inflammatory cells was examined
      immunohistochemically in routinely processed resection specimens of the lumbar
      disc. The histological results were compared to prospectively obtained clinical
      data. Disc specimens of 179 patients who underwent surgery for lumbar disc
      herniation were studied immunohistologically. Preoperatively each patient
      received a visual analogue scale for classification of the pain level and general
      clinical data were recorded prospectively. Varying amounts of inflammatory cells
      could be demonstrated in the resected disc tissue. In the statistical workup no
      statistically significant correlation between the histological evidence of
      macrophage infiltrates and the pain grading scale or the clinical data could be
      found. In our study there is no statistically significant correlation between
      macrophage infiltrates in herniated lumbar disc specimen and the obtained
      clinical data.

PMID- 9932126
TI  - Prognostic factors in postraumatic severe diffuse brain injury.
AB  - It is usually defficult in clinical practice to establish factors affecting final
      outcome in patients suffering severe diffuse brain injury (SDBI), due to the
      absence of specific semiology. METHODS: We studied retrospectively 160
      consecutive patients with criteria of SDBI. We performed a statistical analysis
      of epidemiological, clinical and radiological factors, and relationship with
      final outcome. RESULT: 35% of patients with severe head injury presented SDBI.
      Sixty percent were 15-35 year old and 73% male. More than 45% of the patients
      presented GCS 3 or 4. On CT performed during the first 24 h, haemorrhagic lesions
      appeared in white matter in 35% and subarachnoid haemorrhage was observed in 28%.
      During the first 24 h., 66% of patients presented values of intracranial pressure
      (ICP) above 20 mm Hg and a 33% below 20 mm Hg. Twenty percent of the patients had
      ICP > 20 mm and no response to treatment. According to the Glasgow Outcome Scale
      (GOS), mortality of more than 50% and 25% of patients with persistent vegetative
      state or severe disability were observed. CONCLUSIONS: Clinical evaluation, early
      CT findings, ICP values and their response to medical treatment and clinical
      complications were found to be related (p < 0.05) to final outcome (GOS).

PMID- 9932125
TI  - Anterior cervical decompression and fusion for cervical spondylosis using
      vertebral grafts obtained from the fusion site. Technical advantages and follow
      up results.
AB  - A retrospective analysis was done in 60 consecutive patients who underwent
      anterior cervical fusion using vertebral grafts obtained from the fusion site at
      the Nagoya University and its affiliated hospitals by a single surgeon (MT).
      Follow-up results and technical advantages are reported. The average follow-up
      period was 33 months (range 6 to 55 months). Sufficient decompression of the
      anterior cervical pathology was performed successfully via a wider operative
      field. The symptoms and neurological score improved significantly without any new
      deficits in all patients except in one with a three-level fusion who needed re
      operation for further decompression. No major graft complications such as graft
      extrusion or pseudoarthrosis occurred. Graft fracture was noted in five cases.
      However, good bony fusion was observed in all these cases without any further
      treatment. Normal cervical lordosis was preserved in most cases except in four,
      who lost lordotic alignment but did not show kyphosis. Major advantages of this
      method are a wider operative field, excellent graft fusion rate, and no need for
      an additional incision to obtain autogenous bone graft. These benefits seem have
      to contributed to satisfactory surgical results in this series.

PMID- 9932127
TI  - Current treatment strategies and factors influencing outcome in patients with
      bacterial brain abscess.
AB  - We clearly determined the key to managing patients with brain abscess by
      retrospectively evaluating the factors affecting poor outcome in these patients.
      This study included 113 patients with brain abscess diagnosed in the CT era.
      Basic characteristics and therapeutic parameters were estimated as independent
      predictors of poor outcome by using univariate and multivariate logistic
      regression analysis. Patients with poor outcomes more frequently had deeply
      located abscesses (p < 0.02), IVROBA (intraventricular rupture of brain abscess
      (p < 0.001) and were in a severely deteriorated neurological state (p < 0.001)
      than those with good outcomes. Multiple logistic regression analysis predicted
      that IVROBA (ORs, 24.5; 95% CI, 3.04 to 197.9) and severely deteriorated cases
      (ORs, 13.7; 95% CI, 2.34 to 80.8) resulting from IVROBA increased the relative
      risk of poor outcome. Patients with IVROBA more frequently had also deeply
      located abscesses (p < 0.005), positively immunocompromised states (p < 0.05) and
      were in a severely deteriorated condition (p < 0.003) than those without IVROBA.
      Patients with metastatic abscess had also IVROBA (p < 0.006). Multiple logistic
      regression analysis anticipated that deeply-located abscess (ORs, 3.90; 95% CI,
      1.38 to 11.04), and metastatic abscess (ORs, 12.26; 95% CI, 1.35 to 111.2)
      increased the relative risk of IVROBA. Patients in an obtunded state and with
      marked neurological deficit had IVROBA more often than patients in an alert state
      and/or mild neurological deficit (ORs, 3.23; 95% CI, 1.17 to 8.86, p < 0.03)
      before treatment. Our findings suggest that IVROBA strongly influences poor
      outcome in patients with brain abscess. The key to decreasing poor outcomes may
      be the prevention and management of IVROBA, by evaluating intracranial pressure
      pathophysiology. IVROBA should be aggressively treated by aspiration methods for
      the abscess coupled with appropriate intravenous and intrathecial administration
      of antibiotics.

PMID- 9932128
TI  - The effect of peripheral glycerol on trigeminal neuropathic pain examined by
      quantitative assessment of abnormal pain and sensory perception.
AB  - In nine patients with trigeminal neuropathic pain after nerve injury, we examined
      prospectively the effect of peripheral glycerol neurolysis on abnormal pain and
      sensory perception. In the painful facial skin area of these patients, we found
      increased temperature and tactile thresholds and the presence of abnormal
      temporal summation of pain. In seven patients, neuropathic pain was peripheral
      and disappeared after application of local anaesthesia at or proximal to the site
      of nerve injury. Neuropathic pain was central in two patients, and unresponsive
      to local anaesthesia applied proximal to the site of nerve injury. Six weeks
      after injection of glycerol proximal to the site of nerve injury, no or marginal
      pain relief was found in 8 patients with peripheral or central trigeminal
      neuropathic pain. On the other hand, in one of the patients with peripheral
      trigeminal neuropathic pain, glycerol was given at the site of nerve injury, and
      produced total pain relief for the whole observation period of 7 months. In this
      patient, pain relief was associated with normalisation of abnormal temporal
      summation of pain, which was not observed in the 8 patients with no or marginal
      pain relief. No further changes in temperature or tactile thresholds were found
      in any of the 9 patients after a single injection of absolute glycerol. Total
      pain relief in one of the patients probably is related to the ability of glycerol
      to inhibit ongoing ectopic impulse generation at the site of nerve injury. We
      suggest that glycerol-induced reduction of primary afferent hyperactivity may
      secondarily result in down-regulation of central neuronal hyperexcitability. The
      efficacy of application of glycerol at the site of nerve injury in patients with
      peripheral trigeminal neuropathic pain may warrant further investigation.
      However, this prospective study does not provide evidence that application of
      glycerol proximal to the site of nerve injury has a place in the treatment of
      trigeminal neuropathic pain.

PMID- 9932129
TI  - Neurovascular compression syndrome of the eighth cranial nerve. What are the most
      reliable diagnostic signs?
AB  - Forty-three surgical cases were retrospectively analyzed to establish diagnostic
      criteria and operative indications for vertigo and tinnitus due to neurovascular
      compression (NVC) of the eighth cranial nerve (8th N). Many NVC syndromes were
      mistakenly diagnosed as Meniere's disease or benign paroxysmal positional
      vertigo. NVC was confirmed in 31 of the 43 patients. Neurovascular decompression
      (NVD) resulted in complete recovery or marked improvement of subjective symptoms
      in all 19 cases with vertigo (100%), and in 19 of 29 patients with tinnitus
      (65.5%). Multiple factor analysis revealed that abnormal caloric responses have
      high diagnostic value for vertigo due to NVC. Vertigo due to NVC is of short
      duration (a few sec to a few min.) in the early phase of the disease, which
      becomes longer and hearing becomes impaired as the history of NVC lengthens. Low
      pitch pulsatile and high pitch continuous tinnitus are probably due to NVC and
      are cured by NVD if hearing is still preserved. Tinnitus associated with
      hemifacial spasm is strongly indicative of NVD. Decompression of the 8th N should
      be performed in the early phase of disease, since cochlear and vestibular
      functions are irreversibly impaired if NVC continues for a long period of time.

PMID- 9932130
TI  - Neural activity of the subthalamic nucleus in Parkinson's disease patients.
AB  - The neural activity pattern of the subthalmic nucleus (STN) was investigated in
      five patients with Parkinson's disease who were scheduled for electrode
      implantation for chronic stimulation of the STN. The initial target was placed 8
      mm or 10 mm lateral to the midline, 3 mm to 4 mm posterior to the midcommissural
      point, and 5 mm to 6 mm below the intercommissural (AC-PC) line. The STN was
      identified by semi-microelectrode recordings with a trajectory moving laterally
      in 2-mm steps. The amplitudes of multi-unit activities were relatively low at
      depths from 8 mm to 5 mm above and from 1 mm to 4 mm below the target, while
      those 4 mm to 0 mm above the target were significantly higher than at the other
      sites (ANOVA, Fisher's test, p < 0.05), with the highest amplitude at 2 mm above
      the target (91.0 +/- 23.3 mu v, n = 15). In the mediolateral direction,
      amplitudes were relatively higher in the lateral portion, and amplitudes at 14 mm
      lateral to the midline were significantly higher than at the other sites (ANOVA,
      Fisher's test, p < 0.05). The target for chronic electrical stimulation was
      determined to be at the midpoint of the hyperactive STN, i.e., 12 mm lateral to
      the midline in three patients and 13 mm lateral in two patients. Movement-related
      neural activity was observed at 5 sites, i.e., 3 sites responded to passive
      movement of the contralateral wrist and 2 sites to passive knee and/or ankle
      movement. In conclusion, our data show that the lateral part of the STN is
      hyperactive in PD, and recordings of neural activities contributed greatly to
      identifying the STN and determining the target for chronic stimulation within it.

PMID- 9932131
TI  - The dual-tube microsurgical suction instrument.
AB  - A dual-tube suction instrument intended for both macro- and microsurgery has been
      developed. A detachable air-tight inner tube is fitted into a conventional
      suction instrument; extending the ordinary sucking tube. The inner tube can
      easily be fitted, as well as removed from the other tube; a particular advantage
      in case the inner tube becomes obstructed. On removal of the inner tube the outer
      tube becomes cleaned and is at once, ready for re-use. Since the suction
      instrument does not have to be removed from the suction hose, valuable time is
      saved, enabling permanent sucking capacity.

PMID- 9932132
TI  - Nonselective nerve fibre damage in peripheral nerves after experimental
      thermocoagulation.
AB  - In this study the morphological effects of local heat application by controlled
      thermocoagulation to the sciatic nerve of rabbits are investigated. It
      concentrates on the question of a possible selective elimination of nerve fibres
      depending on their calibers. Temperatures of 50 degrees C, 55 degrees C, 60
      degrees C, 70 degrees C and 90 degrees C were applied for 45 seconds. The nerves
      were examined histologically after 2-3 minutes, 7 and 12 days and 5 weeks. The
      light and electronmicrographs show no differential vulnerability of small
      myelinated or unmyelinated fibres as proposed by Sweet and Wepsic [20]. At a
      temperature of 50 degrees C no fibre is damaged whereas at 60 degrees C the fibre
      damage extends over nearly the total cut surface of the nerve. Even at the
      critical temperature of 55 degrees C affecting only part of the cross-section no
      predilection of any fibre caliber was observed. In summary thermocoagulation
      seems not to be able to cause selective fibre damage.

PMID- 9932133
TI  - The effect of aprotinin on extraneural scarring in peripheral nerve surgery: an
      experimental study.
AB  - Extraneural scarring is one of the factors negatively influencing the result of
      peripheral nerve surgery. Many organic materials have been used to prevent
      fibrosis. The effect of aprotinin on peripheral nerve scarring in rats was
      investigated in this study. Three types of surgical intervention were carried
      out; namely external neurolysis (I), abrasive injury (II), and anastomosis (III).
      The coded samples which consisted of pure collagen fibers soaked with aprotinin
      or phosphate-buffered saline were applied around the left sciatic nerves of rats
      whereas only sham operations were performed on the right sciatic nerves. Animals
      were sacrificed after 4 or 6 weeks. Neurological examination, gross evaluation of
      extraneural fibrosis, and histological study were undertaken. The results have
      demonstrated that aprotinin is a promising agent in the prevention of extraneural
      scarring.

PMID- 9932134
TI  - Intraoperative direct electrical stimulation of the lamina quadrigemina in a case
      of a deep tectal cavernoma.
AB  - Despite the recent neuro-imaging and microsurgical advances, a high rate of
      postoperative morbidity still remains in brain stem surgery. We report an
      original case of cavernous angioma of the right inferior colliculus without
      extension to the surface, operated on using brain stem electrical stimulations.
      Peroperative ocular motor responses were obtained, allowing identification of
      essential neural structures before dissection of the brain stem surface, and
      accurate definition of the limits between the lesion and functional tissue in
      depth. Total removal of cavernoma and surrounding gliosis was then performed,
      with normal postoperative neurological status. As already reported at the
      cortical level, peroperative direct brain stem stimulations constitute a safe and
      easy method of functional mapping. A more intensive use of this
      neurophysiological technique might permit one to extend the indications for brain
      stem surgery, with minimisation of postoperative morbidity and maximisation of
      tumour resection.

PMID- 9932135
TI  - Middle cerebral artery aplasia associated with an aneurysm of the proximal
      anterior cerebral artery.

PMID- 9932136
TI  - Footdrop as an initial manifestation of an intramedullary metastatic bronchial
      carcinoma.

PMID- 9932137
TI  - Meningioma associated with chronic subdural hematoma.

PMID- 9932138
TI  - Practical issues in cognitive screening of elderly illiterate populations in
      developing countries. The Indo-US Cross-National Dementia Epidemiology Study.
AB  - The study of the epidemiology of dementia, specifically Alzheimer's disease, in
      developing countries requires specialized instruments and personnel. Cultural and
      sub-cultural differences among populations are highly relevant to the design of
      such instruments. Over and above the cultural issues, it is widely recognized
      that low education and illiteracy pose considerable challenges to reliable and
      valid cognitive screening. The overall objectives of the Indo-US Cross-National
      Dementia Epidemiology Study were: a) to determine the prevalence and incidence
      of, and risk factors for, Alzheimer's and other dementias in a defined Indian
      community; and b) to compare these results with those found in a defined American
      community. To achieve these epidemiological objectives, our first task was to
      develop, systematically and empirically, suitable cognitive and activities
      assessment screening instruments for use in India, which would 1) be culturally
      fair, psychometrically sound, and valid for a population with little or no
      education; 2) be optimally sensitive and specific for dementia; and 3) allow not
      only the identification but also the more detailed characterization of dementia,
      and of normal and abnormal cognitive aging. In this paper we address the
      practical issues involved in the development and administration of the modified
      cognitive screening battery in our rural Indian context.

PMID- 9932139
TI  - Anticipation of and adjustment to retirement.
AB  - The role of anticipation of retirement was studied by comparing two samples under
      different conditions: in the West German sample, retirement could be anticipated
      as "normal" with regard to the economic changes in most industrial societies
      between 1992 and 1994, whereas the members of the East German sample were faced
      with mandatory retirement, with few changes in the anticipation of this event.
      Findings confirm the hypotheses regarding a more negative view of retirement,
      different ways of coping with retirement, and equal status of cognitive
      functioning and health. They did not confirm the hypothesis of a lower degree of
      well-being in the East.

PMID- 9932140
TI  - Aims, design and enrollment rate of the Cardiac Rehabilitation in Advanced Age
      (CR-AGE) randomized, controlled trial.
AB  - Data regarding the efficacy of cardiac rehabilitation after acute myocardial
      infarction in advanced age are limited, and are derived from either controlled
      but non randomized trials, or observational studies. Several aspects of cardiac
      rehabilitation after myocardial infarction in advanced age, including its
      effectiveness on exercise tolerance and health-related quality of life, as well
      as the feasibility of rehabilitation programs, need clarification. The objectives
      of this randomized, controlled trial, Cardiac Rehabilitation in Advanced Age (CR
      AGE), are to examine the effects of an 8-week comprehensive cardiac
      rehabilitation intervention, comparing 1) supervised outpatient, hospital-based
      cardiac rehabilitation, 2) home-based cardiac rehabilitation, and 3) usual care
      in each of three groups of post-myocardial infarction patients, 45-65, 66-75, and
      76-85 years of age. The primary objective of the trial is to evaluate the change
      in physical fitness in each age group assessed by total work capacity at the end
      of the intervention, and during follow-up over both the medium- (6 months) and
      the long-term (1 and 2 years). Secondary objectives of the trial include an
      examination of the feasibility of cardiac rehabilitation in older patients, as
      well as the determination of the following: exercise complication rates; changes
      in peak oxygen consumption; changes in other outcome measures, such as health
      related quality of life, prevalence of anxiety and depressive symptoms, fluid
      intelligence, body composition and mass index; incidence of new cardiac and non
      cardiac events; and utilization rates of health care services. Enrollment in the
      CR-AGE trial is expected to be completed within the first half of 1998.

PMID- 9932141
TI  - Sense of coherence, quality of life, and function among elderly hip fracture
      patients.
AB  - The aim was to study whether sense of coherence (SOC) had any predictive power in
      patients with hip fractures regarding length of stay in hospital, state of
      confusion and health, functional ability, quality of life, and municipal home
      help service. A total of 73 patients admitted from their own homes participated
      (mean age 80.4 years). The patients were followed during a 4-month period. Acute
      confusional state was diagnosed using a Swedish version of the NEECHAM Confusion
      Scale. SOC and self-rated functional health status were assessed during the
      hospitalization period and one month after discharge; Quality of Life Index (QLI)
      and instrumental daily activities (SPE) were assessed four months after
      discharge. Focusing on the differences in outcome between persons with a stronger
      vs a weaker SOC, there were few significant differences in physical status
      between the subgroups. However, the persons with a weaker SOC stayed longer in
      the hospital and reported a significantly lower score on the NEECHAM Confusion
      Scale, as well as more discomfort and disability symptoms related to
      communication, mental, and emotional status. Furthermore, these persons had less
      favorable scores on the overall QLI and subscales respectively, and on all
      subscales measuring instrumental daily activities. The persons with a weaker SOC
      were significantly more dependent on assistance before admission to the hospital
      than those with a stronger SOC. The conclusions drawn from the study indicate
      that persons with a stronger SOC seem to cope in a better way with their
      situation after a hip fracture.

PMID- 9932143
TI  - Developing a summary measure of medical status.
AB  - Health status surveys and assessments typically obtain detailed information on
      specific physical health conditions. While such specific details are important,
      it is frequently also valuable to have a summarized evaluation of medical
      conditions which can be used to compare subjects, or for statistical analyses.
      Using data from the Duke Established Populations for Epidemiologic Studies of the
      Elderly survey, we indicate how to obtain a weighted sum of chronic medical
      conditions. Like the sum of the same conditions, it explains variance in selected
      measures of health service use and health status, in some instances making a
      contribution beyond that of the summed measure. It is a significantly better
      predictor of mortality within six years.

PMID- 9932142
TI  - Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile
      osteoporosis.
AB  - Recent animal work suggests that gamma-linolenic acid (GLA) and eicosapentaenoic
      acid (EPA) enhance calcium absorption, reduce excretion and increase calcium
      deposition in bone. A pilot study was set up to test the interactions between
      calcium and GLA + EPA in humans. Sixty-five women (mean age 79.5), taking a
      background diet low in calcium, were randomly assigned to GLA + EPA or coconut
      oil placebo capsules; in addition, all received 600 mg/day calcium as the
      carbonate. Markers of bone formation/degradation and bone mineral density (BMD)
      were measured at baseline, 6, 12 and 18 months. Twenty-one patients were
      continued on treatment for a second period of 18 months, after which BMD (36
      months) was measured. At 18 months, osteocalcin and deoxypyridinoline levels fell
      significantly in both groups, indicating a decrease in bone turnover, whereas
      bone specific alkaline phosphatase rose indicating beneficial effects of calcium
      given to all the patients. Lumbar and femoral BMD, in contrast, showed different
      effects in the two groups. Over the first 18 months, lumbar spine density
      remained the same in the treatment group, but decreased 3.2% in the placebo
      group. Femoral bone density increased 1.3% in the treatment group, but decreased
      2.1% in the placebo group. During the second period of 18 months with all
      patients now on active treatment, lumbar spine density increased 3.1% in patients
      who remained on active treatment, and 2.3% in patients who switched from placebo
      to active treatment; femoral BMD in the latter group showed an increase of 4.7%.
      This pilot controlled study suggests that GLA and EPA have beneficial effects on
      bone in this group of elderly patients, and that they are safe to administer for
      prolonged periods of time.

PMID- 9932144
TI  - Memory-scanning task performance in Alzheimer's disease.
AB  - Individuals with mild Alzheimer's Disease (AD) and healthy normal control (NC)
      older adults performed a varied-set version of the Sternberg memory-scanning task
      with Set Sizes 1, 2, 3, and 4. The AD group (N = 23) had slower and more variable
      reaction times (RT) than the NC group (N = 38). RT differences between groups
      were bigger for NO than for YES responses. The linear relationship between RT and
      set size was not as strong for the AD group as for the NC group. However, in
      contrast to earlier studies with fewer subjects, participants with AD and healthy
      older individuals did not differ in the rate at which they scan items in the
      memory set.

PMID- 9932145
TI  - Predictors of pain self-report in nursing home residents.
AB  - The purpose of this study was to examine the influence of cognitive function and
      other biopsychosocial factors on test-retest agreement, four-week variability,
      and intensity of self-reported pain using the verbal 0 to 10 scale and a pain
      thermometer in 115 nursing home residents over four weeks. Pain was assessed
      twice on three days during week 1, and once each during weeks 2, 3 and 4. A
      forward stepwise regression procedure was used to examine the influence of
      biopsychosocial parameters (age, race, gender, educational status, marital
      status, comorbidity, cognitive function, depression, social support, physical
      function and self-rated health) on pain intensity, test-retest agreement and
      variability. There was a quadratic association between cognitive function and
      test-retest agreement with the 0-10 scale; residents with Folstein scores of 22
      26 were more likely to show disagreement (50% of 34) than residents with scores <
      22 or > 26 (7% of 71). Higher Folstein scores were also associated with greater
      pain intensity for both pain scales (p < 0.001). Baseline pain intensity was
      significantly related to pain variability (0-10 scale only). The clinician should
      be cognizant of these relationships when interpreting verbalizations of pain in
      long-term care facilities.

PMID- 9932146
TI  - Impact of aging on human salivary gland function: a community-based study.
AB  - A comprehensive evaluation of salivary flow rates and composition was undertaken
      in an age- and community-stratified population. A nonmedicated subpopulation was
      used to assess the effect of "primary aging" on salivary gland function.
      Unstimulated whole, parotid and submandibular/sublingual (SMSL) saliva, as well
      as citrate-stimulated parotid and SMSL saliva were collected from 1006 subjects.
      Flow rates were determined, and the total protein concentrations measured. Height
      and caloric intake were documented. Subjects were divided into six age groups
      from 35 to 75+ years old. Significant age-related decreases in the secretion
      rates of unstimulated whole (p < 0.001), stimulated parotid (p < 0.01) and
      unstimulated and stimulated SMSL (both p < 0.0001) saliva were observed in the
      total population. In the non-medicated subpopulation, age-related decreases in
      salivary secretions were observed in unstimulated whole (p < 0.01) and
      unstimulated and stimulated SMSL (p < 0.01 and p < 0.0001, respectively).
      Multiple regression analysis revealed that, as well as age, caloric intake was
      related to unstimulated SMSL and stimulated SMSL saliva in the whole population,
      and height was a contributor to unstimulated whole saliva and unstimulated
      parotid saliva flow rate variances. In the non-medicated population, caloric
      intake was the significant independent variable for unstimulated and stimulated
      parotid secretion, as was height for unstimulated whole and SMSL flow rates. Age
      related increases in the total protein concentration of unstimulated parotid (p <
      0.001) and unstimulated SMSL (p < 0.05) saliva were evident in the whole
      population, but not in the non-medicated subgroup. These data suggest that there
      are significant age-related alterations in salivary function.

PMID- 9932151
TI  - WHO in search of cancer strategies for the new millennium.

PMID- 9932152
TI  - Prostate specific antigen (PSA) testing as screening for prostate cancer: the
      current controversy.

PMID- 9932153
TI  - Gemcitabine--a major advance?

PMID- 9932154
TI  - The detection of minimal numbers of contaminating epithelial tumor cells in blood
      or bone marrow: use, limitations and future of RNA-based methods.
AB  - BACKGROUND: Many solid tumors commonly metastasize to the bone marrow and the
      presence of tumor cells in the bone marrow is associated with a poor prognosis.
      Detection of tumor cells in the bone marrow has been reported to be important to
      determine the prognosis of newly diagnosed patients and may be helpful in
      deciding whether or not systemic treatment is indicated. PATIENTS AND METHODS:
      The majority of the studies focus on the detection of tumor cells in non-tumor
      tissue using immunocytochemistry and antibodies directed against epitopes of
      epithelial genes. Recently, the sensitive reverse-transcriptase polymerase chain
      reaction (RT-PCR) has been employed for the detection of tumor cells in bone
      marrow, using mRNA transcribed from epithelial genes as targets for RT-PCR.
      RESULTS: In some studies, encouraging results were reported when RT-PCR was used
      to detect expression of epithelial genes, but in many others frequent false
      positive results were observed. These may results from the 'illegitimate
      expression' of epithelial genes in cells of non-epithelial tissues, such as bone
      marrow. CONCLUSIONS: Micrometastases in bone marrow can be detected with some
      sensitivity by antibodies directed against epithelial genes. RNA based methods,
      using epithelial genes as target for amplification, are less reliable. To improve
      these methods, a systematic approach is required to identify genes which are
      highly expressed in solid tumors and completely silent in blood and bone marrow
      of healthy individuals. Novel techniques, e.g., 'sequential analysis of gene
      expression (SAGE), are now available that allow such an endeavor.

PMID- 9932155
TI  - PSA screening for prostate cancer: the current controversy--a viewpoint. Patient
      Outcomes Research Team for Prostatic Diseases.
AB  - Prostate cancer is an important health problem. Randomized trials have not yet
      proven whether or not screening with prostate-specific antigen measurements
      reduces morbidity or mortality. The potential for overtreatment of prostate
      cancers not destined to cause future mortality, the uncertainty about the
      benefits of aggressive treatment of screen-detected cancers, and the relatively
      high costs of prostate cancer screening programs are all areas of concern. A
      shared approach to decisions about screening individual patients pending better
      evidence is one strategy for clinicians to consider in dealing with this
      controversial problem.

PMID- 9932156
TI  - PSA screening--current controversy.
AB  - There is perhaps no more contentious issue in Urology in 1998 than how and if PSA
      screening for prostate cancer should be applied. The issue must be discussed in
      the absence of completed randomized clinical trials, and arguments must be
      supported by extrapolated clinical data in the medical literature. Because of
      data which can be interpreted often in two different manners, groups and
      organizations including patient's groups, governmental agencies, medical
      organizations, and managed care providers often find themselves at odds with each
      other with regards to recommendations regarding PSA screening. In order to put
      these issues into perspective, a series of five questions will be answered.

PMID- 9932157
TI  - Screening for prostate cancer.

PMID- 9932158
TI  - PSA screening for prostate cancer: the current controversy.

PMID- 9932159
TI  - Overdiagnosis of prostate carcinoma by screening: an estimate based on the
      results of the Florence Screening Pilot Study.
AB  - OBJECTIVES: To estimate overdiagnosis (detection of latent carcinomas) as a
      consequence of screening for prostate cancer. DESIGN: Based on actual screen
      (first or repeat) detected and interval prostate cancer rates observed in the
      Florence screening pilot study, a scenario was simulated where males aged 60
      years (or 65) had six biennal screens and were followed up for four years.
      Overdiagnosis was determined as the proportional excess of cancers detected by
      screening with respect to that expected in its absence. SETTING: City of
      Florence, Italy, from 1992 through 1995. POPULATION: 2,740 resident males, aged
      60 to 74 years. RESULTS: Overdiagnosis was estimated to be 51% (95% confidence
      limits: 44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with
      other screening experiences obtaining higher detection rates suggests that a more
      aggressive screening approach could be associated with overdiagnosis estimates as
      big as 200%-250%. CONCLUSIONS: Screening for prostate cancer is associated with a
      relevant risk of overdioagnosis. As latent carcinomas can not be presently
      identified, this would lead to overtreatment in most overdiagnosed cases. The
      negative consequences of overdiagnosis (knowledge of having a cancer) and of
      overtreatment (impotence, incontinence, perioperatory death) may be extremely
      serious. In absence of any scientific evidence of screening benefits (if any)
      screening should not be recommended as a current practice, but should be limited
      to prospective controlled studies designed to assess its cost-effectiveness.

PMID- 9932160
TI  - Long-term results from a phase II study of single agent paclitaxel (Taxol) in
      previously platinum treated patients with advanced ovarian cancer: the Nordic
      experience.
AB  - BACKGROUND: Owing to the wide spread perception of a possible benefit from
      paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group
      (NGOG) conducted two prospective phase II studies of paclitaxel single agent
      treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every
      third week) in patients with relapsing or progressing epithelial ovarian cancer
      following platinum. PATIENTS AND METHODS: Between 1992-1994 138 patients in total
      were enrolled of whom 136 received paclitaxel and were included in the toxicity
      and survival analysis, while 112 were evaluable for response. RESULTS: The
      overall response rate (CR + PR) was 28% with 16 patients achieving a CR (14%).
      The estimated median (range) time to progression was 4.1 (0.7-60.7) months. The
      projected four-year overall survival was 7%, with a median (range) of 9.6 (0.3
      60.7) months. A multivariate logistic regression analysis showed that platinum
      resistance, and WHO performance status at baseline, independently correlated with
      survival at all three time points (median survival time 9.6, 18, and 24 months).
      Patients with platinum sensitive tumors and WHO performance status 0 had a median
      survival of 25.6 months compared to 7.0 months for the rest of the patients (P <
      or = 0.0001). No serious toxicity was registered. CONCLUSION: Paclitaxel could
      safely be administered in an outpatient setting using this schedule. Patients
      with platinum sensitive tumors and a good performance status were most likely to
      survive. However, these patients are also most likely to respond to re-treatment
      with a platinum compound. With reference to the reasonably good tumor control and
      limited toxicity observed in this study, we conclude that paclitaxel single agent
      therapy is a viable option in the salvage situation, which in some patients can
      give long-lasting responses. However, although responses can be induced in a
      significant number of patients, the survival figures remain poor.

PMID- 9932161
TI  - 5-methyltetrahydrofolate for biochemical modulation of fluorouracil (FU) in
      patients with advanced colorectal cancer: a randomized phase I-II study of two
      different FU administration schedules.
AB  - BACKGROUND: To determine the maximum tolerable dose (MTD) and therapeutic
      activity of MTHF-modulated FU using two different administration schedules of the
      antimetabolite (bolus vs. two-hour infusion), the present randomized study using
      a 'pick-the-winner' design was undertaken in patients with advanced colorectal
      cancer. PATIENTS AND METHODS: Eighty-two patients with previously untreated
      advanced measurable colorectal cancer were randomly assigned to treatment with
      MTHF (100 mg/m2 days 1-5 i.v. bolus) plus FU (400 mg/m2 days 1-5) given either as
      i.v. bolus injection or as a two-hour infusion every four weeks. In the absence
      of dose-limiting toxicity (DLT, defined as > or = WHO grade 3 hematotoxicity
      and/or > or = WHO grade 2 nonhematologic side effects) and evidence of
      progressive disease, the FU dose was escalated by 50 mg/m2/day during each
      subsequent cycle until the individual maximum tolerable dose (MTD) was reached.
      RESULTS: Forty patients were randomized to the FU bolus arm and 42 patients to
      the FU two-hour infusion arm. The median MTD was 475 mg/m2/day (95% CI: 450-500)
      in the FU bolus arm with stomatitis +/- diarrhea being the most common DLT.
      Gastrointestinal side effects were also dose-limiting in the two-hour infusion
      arm; however, the median MTD was 600 mg/m2/day (95% CI: 568-632).
      Myelosuppression was more pronounced in the FU bolus arm than in the two-hour
      infusion arm. The overall response rates were 27.5% (95% CI: 15-44%; 1 CR and 10
      PR) for patients treated in the bolus arm and 14.5% (95% CI: 5-28%; 1 CR and 5
      PR) for those treated in the two-hour infusion arm. Analogous to recorded
      response, median time to progression (8.5 vs. 6.25) and overall survival time
      (14.0 vs. 11.0) tended to be superior in the FU bolus arm. CONCLUSIONS: The
      observed differences in tolerable drug dose and toxicity between the two
      treatment arms might be explained by the administration schedule-dependent
      clinical pharmacokinetics of FU and/or the difference in extent of biochemical
      modulation of the antimetabolite through MTHF. The fact that the two regimens
      were not equitoxic probably also helps to explain the favourable response
      activity noted in the MTHF/FU bolus arm. Whether MTHF is as effective as
      leucovorin for biochemical modulation of FU remains to be determined in a
      randomized trial, for which we would recommend its combined use with bolus FU
      ('winner arm') using a starting dose of 400 mg/m2/day x5.

PMID- 9932162
TI  - Phase I clinical and pharmacokinetic study of the oral platinum analogue JM216
      given daily for 14 days.
AB  - BACKGROUND: The oral bis (acetate) ammine dichloro cyclohexylamine platinum (IV)
      analogue (BMS-182751) was brought into clinical development because it was shown
      to be cytotoxic against some human tumour cell lines and to have an antitumor
      activity in murine tumours at least comparable to that of parenteral cisplatin
      and carboplatin. In early clinical studies in which the optimal schedule of
      treatment was daily for five consecutive days, dose-dependent nausea and vomiting
      occurred in about two-thirds of patients. PATIENTS AND METHODS: To evaluate if
      the use of lower daily doses for longer periods of time could result in a better
      tolerability, JM216 was given once daily for 14 consecutive days every four to
      five weeks to adult patients with solid tumors. Oral antiemetics were given
      prophylactically only at the highest doses. The pharmacokinetics of total and
      ultrafiltrable platinum were studied on days 1 and 14 of the first cycle by
      Inductively Coupled-Mass-Spectrometry (ICP-MS). RESULTS: Forty-six patients were
      treated at doses ranging from 10 mg/m2/d to 50 mg/m2/d and 39 were evaluable for
      hematologic toxicity over 74 cycles. MTDs were reached at 45 mg/m2/d and 50
      mg/m2/d x 14 repeated every five weeks in patients with extensive, or limited/no
      prior treatment, respectively. The dose-limiting toxicity was neutropenia which
      was delayed and variable among patients. Other non-hematological toxicities were
      severe vomiting (22% of cycles), diarrhea (28% of cycles) and drug-associated
      fever (32% of patients), controlled with paracetamol. Subjective improvement with
      disappearance of tumour-related pain was observed in one patient with
      chemotherapy-resistant metastatic prostate cancer and in one previously untreated
      patient with malignant mesothelioma. Cmax and AUC values of both total and
      ultrafiltrable platinum on days 1 and 14 were highly variable among patients.
      Only Cmax on day 1 was linearly related to the dose. Total and ultrafiltrable
      platinum were still detectable two weeks after the last dose. No relationship
      could be established between AUC values and toxicities. CONCLUSIONS: Daily doses
      of JM216 of 40 mg/m2 and 45 mg/m2 for 14 consecutive days every five weeks with
      oral antiemetic prophylaxis are selected for phase II evaluation of single agent
      in patients with extensive or limited/no prior treatment, respectively. The
      administration of JM216 on a day x 14 schedule produced nausea and vomiting
      comparable to that observed with the day x 5 regimen but of longer duration. The
      variability of pharmacokinetics and pharmacodynamics, even though limited at the
      doses proposed for phase II evaluation of JM216 as single agent, recommend a
      careful monitoring of the patients.

PMID- 9932163
TI  - Clinical and pharmacologic phase I study of Cemadotin-HCl (LU103793), a novel
      antimitotic peptide, given as 24-hour infusion in patients with advanced cancer.
      A study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) Phase I Group
      and Arbeitsgruppe Pharmakologie in der Onkologie und Haematologie (APOH) Group of
      the German Cancer Society.
AB  - PURPOSE: To determine the maximum tolerable dose (MTD), principal toxicity, and
      pharmacologic behaviour of Cemadotin-HCl, a novel antimitotic peptide. PATIENTS
      AND METHODS: Cemadotin-HCl (10.0 to 27.5 mg/m2/day every three weeks) was
      administered as a 24-hour intravenous (i.v.) continuous infusion to patients with
      advanced cancer. Pharmacokinetic analyses were performed during the first
      treatment cycle. Blood samples were taken over 48 hours and analyzed by
      radioimmunoassay. RESULTS: Hypertension was the dose-limiting toxicity (DLT).
      This type of toxicity was observed at all dose levels, but grade 3 (CTC) was
      observed only at dose levels 20.0, 25.0 and 27.5 mg/m2. This effect was
      reversible but in three patients associated with signs of cardiac ischemia. Other
      significant toxic effects were neutropenia, asthenia, tumor pain and transient
      liver enzyme elevation. A linear pharmacokinetics was observed. The best curve
      fit was obtained with a two-compartment model with a terminal half-life of
      approximately 10 hours at each dose level, a volume of distribution at steady
      state of approximately 9 l/m2 and a total clearance of approximately 0.6
      l/hour/m2. Neither partial nor complete responses were observed although minor
      tumor regressions were seen in a patient with carcinoma of unknown primary (CUP)
      and in another patient with liver metastases from a colon cancer. CONCLUSIONS:
      Hypertension was the dose-limiting toxicity of Cemadotin-HCl administered as a
      continuous 24-hour infusion. The recommended dose for further evaluation of its
      anticancer efficacy in disease-oriented phase II studies with this schedule is
      15.0 mg/m2. The nature of the principal cardiovascular toxicity remains unclear.
      The observed toxicities appeared to be significant but manageable.

PMID- 9932164
TI  - Cisplatin combination chemotherapy induces a fall in plasma antioxidants of
      cancer patients.
AB  - BACKGROUND: Antioxidants protect the body against cellular oxidative damage and
      thus some of the adverse effects induced by cisplatin and other cytostatic drugs.
      PATIENTS AND METHODS: The effect of cisplatin-combination chemotherapy on
      concentrations of plasma antioxidants was studied in 36 cancer patients,
      including osteosarcoma and testicular carcinoma patients. RESULTS: Eight to 15
      days after the start of each cytostatic drug infusion concentrations of various
      plasma antioxidants were measured and compared to pretreatment values: vitamin C
      and E, uric acid and ceruloplasmin levels fell significantly (P < 0.01-0.005) and
      returned to baseline levels before the start of the next chemotherapy cycle.
      Levels of the antioxidants bilirubin albumin and the ratio vitamin E/cholesterol
      + triglycerides measured three weeks after the start of chemotherapy
      significantly decreased compared to pretreatment levels and remained low
      thereafter (P < 0.001-0.002). Dietary intake of antioxidants and anthropometric
      measurements, evaluated in 14 patients did not change during the whole treatment
      period. CONCLUSIONS: Cisplatin-combination chemotherapy induces a fall in plasma
      antioxidant levels, that may reflect a failure of the antioxidant defense
      mechanism against oxidative damage induced by commonly used anticancer drugs.
      This probably results from consumption of antioxidants caused by chemotherapy
      induced-oxidative stress as well as renal loss of water-soluble, small molecular
      weight antioxidants such as uric acid.

PMID- 9932165
TI  - Chylopericardium of neoplastic aetiology.
AB  - Here we present the case of a 30-year-old man diagnosed with a dysgerminoma with
      mediastinal involvement, who developed an isolated chylopericardium during
      treatment. The purpose of this paper is to review the etiology, diagnosis and new
      approaches to the treatment of chylopericardium.

PMID- 9932166
TI  - A phase II study of gemcitabine in platinum pre-treated patients with advanced
      epithelial ovarian cancer.
AB  - BACKGROUND: Most patients with advanced ovarian cancer will relapse following
      platinum-based combination chemotherapy and be considered for second-line
      treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid
      tumors. This phase II study investigated the activity of single-agent gemcitabine
      in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight
      patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously
      treated with platinum-containing regimens were enrolled. Patients received 1200
      mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients
      completed an average of 3.6 cycles. Two complete and three partial responses were
      seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI:
      4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally
      mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported
      in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary
      toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in
      patients with recurrent ovarian cancer.

PMID- 9932167
TI  - Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma
      of the head and neck.
AB  - BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined
      with gemcitabine in patients with irresectable locally recurrent or metastatic
      squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine
      was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of
      50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a
      median age of 59 years (range 42-74) were included. All patients were evaluable
      for toxicity and 22 patients were assessable for response. Eleven cases had
      advanced recurrent locoregional disease while 13 patients had metastatic disease.
      One CR (4.7%) and four PR (18%) were observed, for an overall response rate of
      22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3
      4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most
      significant non-hematological toxicity was asthenia grade 2-3 in 24% of the
      cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a
      favourable toxicity profile with a discrete activity in patients with locally
      recurrent or metastatic squamous-cell carcinoma of the head and neck.

PMID- 9932168
TI  - Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients.
AB  - BACKGROUND: Gemcitabine is a novel nucleoside analogue which has shown promising
      results in most solid tumors; like the arabinosylcytosine analogue, gemcitabine
      may be an active drug in lymphoproliferative malignancies. We tested it in
      pretreated peripheral T-cell lymphoma patients with isolated skin involvement.
      PATIENTS AND METHODS: We performed a phase II study with the drug in 13
      pretreated patients with peripheral T-cell lymphoma, five of whom had advanced
      stage mycosis fungoides (MF), and eight peripheral T-cell lymphoma unspecified
      (PTCLU). Patients were treated on days 1, 8, and 15 of a 28-day schedule at the
      dosage of 1200 mg/m2 for a total of three courses. RESULTS: Of the 13 patients,
      one achieved complete response (CR) and eight achieved partial responses (PR);
      the remaining four showed no benefit from the treatment. Among the responders,
      one CR and four PR were documented in the PTCLU patients and four PR in MF
      patients. Treatment was well tolerated; hematologic toxicity was mild and no
      nausea/vomiting or organ toxicity was recorded. CONCLUSIONS: In view of its
      significant activity and its modest toxicity profile, the role of gemcitabine
      deserves further evaluation in the management of pretreated patients with
      peripheral T-cell lymphoma.

PMID- 9932169
TI  - Hemolytic-uremic syndrome caused by gemcitabine.

PMID- 9932170
TI  - Aggressive bowel lymphoma in a patient with intestinal lymphangiectasia and
      widespread viral warts.

PMID- 9932171
TI  - Medication knowledge extends beyond closed doors.

PMID- 9932172
TI  - Lymphoscintigraphy.

PMID- 9932173
TI  - Labeling operative sites.

PMID- 9932174
TI  - Hypospadias repair in the 1990s.
AB  - Hypospadias is a congenital anomaly in which the urethral meatus is abnormally
      located anywhere from the glans to the perineum. Refinements in pediatric
      anesthesia, surgical technique and instrumentation, and a greater understanding
      of the psychologic and emotional issues related to hypospadias repair have led to
      this procedure being performed at an earlier age. The goal of reconstruction is
      to bring the urethral meatus to the tip of the penis, to correct associated
      penile curvature if present, to create a conical-shaped glans, and to achieve
      cosmetically acceptable penile shaft skin coverage. The surgical technique
      employed varies with the penile anatomy and surgeon's preference. Complications
      may occur both immediately and long after the surgical procedure, and thus follow
      up is necessary.

PMID- 9932175
TI  - Taking the mystery out of ureteroscopy.
AB  - Ureteroscopy can be one of the more challenging procedures performed in the
      urology department. For perioperative nurses who rotate through the urology
      department and are not familiar with the various stents, wires, baskets, and
      other specialty equipment, the procedure is not only challenging, but also
      mysterious. This article enhances nurses' knowledge of urology by describing the
      steps and equipment of ureteroscopy, including access (i.e., using wires,
      ureteral catheters, and specialty catheters); dilation (i.e., using balloons,
      self-dilating scopes, and sequential and coaxial dilation); manipulation (i.e.,
      using baskets, graspers, biopsy devices, and intracorporeal lithotripsy
      equipment); and stenting (i.e., using multilength or pigtail stents). Knowledge
      of these factors can help clear up the mystery of ureteroscopy, allowing nurses
      to better understand the procedure and better manage its complex inventory.

PMID- 9932176
TI  - Preoperative considerations with herbal medicines.
AB  - More patients are using herbal remedies. Even though herbs are natural products,
      they often act like medications and may interact with or potentiate other
      medications. During a preoperative evaluation, nurses should ask patients about
      their use of herbal remedies. Certain herbs are dangerous and should never be
      taken, and others must be avoided before elective surgery. Today's perioperative
      health care professionals must become familiar with basic information about herbs
      to carry out thorough assessments. At times, caregivers may need to educate and
      counsel consumers about benefits and harmful aspects of herbal preparations.

PMID- 9932177
TI  - Redesigning medication distribution systems in the OR.
AB  - Detroit Riverview Hospital's surgery suite recently converted to an automated
      medication distribution system. Focusing on control, access, documentation, and
      charging, the redesign has benefited pharmacists, nurse anesthetists, and OR
      nurses. Automation reduced nursing labor associated with ordering and restocking
      medications, counting narcotics, and investigating discrepancies. Storage and
      dispensing options, including innovative anesthesia trays, facilitate caregiver
      productivity, quality initiatives, and clinical pathways. System documentation
      pinpoints questionable events and patterns to ensure that all medications
      dispensed were administered to patients. Charges are captured and posted
      automatically. Overall, automated medication distribution has helped the OR
      improve clinical care quality and patient service.

PMID- 9932178
TI  - Management of hysteroscopic surgery complications.
AB  - Hysteroscopic surgery is considered a safe, routine gynecologic procedure
      performed in the OR and in office settings. Complications are rare; however, when
      complications do occur they can be severe and rapid. The surgical team members
      must understand the significance of patient monitoring and proper equipment
      operation to ensure positive patient outcomes. This article discusses
      complications from intravasation of various distending media used during
      hysteroscopy and the complication of hyponatremia. A physiologic approach to
      these problems enhances awareness of the significance of patient monitoring
      during hysteroscopic procedures.

PMID- 9932179
TI  - Basic electrocardiogram interpretation for the OR nurse.
AB  - A basic understanding of electrocardiogram (EKG) interpretation is necessary for
      all perioperative nurses. This includes knowledge of the conduction system of the
      heart and skill at identification of normal and abnormal EKG rhythms. This
      article discusses basic EKG interpretation for OR nurses.

PMID- 9932180
TI  - Warming up to better surgical outcomes.

PMID- 9932181
TI  - Hyperthyroidism in elderly patients.
AB  - Hyperthyroid disorders occur in older people and often are present with atypical
      findings or as apathetic hyperthyroidism. Hyperthyroidism exacerbates underlying
      chronic disease, especially cardiovascular conditions. Elderly people can be
      treated successfully and stabilized with careful screening, astute diagnostics,
      and appropriate therapy.

PMID- 9932183
TI  - Urology sites on the Internet and search tips for Internet browsers.

PMID- 9932184
TI  - Magnetic resonance imaging in lateral epicondylitis of the elbow.
AB  - The purpose of the study was to determine the changes that might be detected
      using magnetic resonance imaging (MRI) on patients with chronic lateral
      epicondylitis of the elbow and to judge its value concerning the clinical
      treatment. Thirty-four patients with chronic lateral epicondylitis were included
      in a prospective study. All individuals underwent MRI of the elbow on a 0.2-T
      dedicated system. The MRI findings were interpreted by an independent radiologist
      without knowledge of the clinical findings. In 6 surgical cases an additional
      histological study was done. The biopsy of the extensor tendon was performed for
      correlation with the MRI. In 21 of 34 symptomatic patients, increased signal
      changes in T1- and T2-weighted images were seen. In a further 11 cases, the
      morphology and signal intensity were normal. The histopathological analysis of 6
      surgical cases confirmed the preoperative MRI findings by showing either focal
      fibrous degenerative tendon tissue or microruptures of collagenous fibres. MRI in
      patients with chronic lateral epicondylitis can help to differentiate the disease
      and may be of use in clinical management, preoperative planning, and in the
      evaluation of the degree of degeneration at the common extensor tendon insertion.

PMID- 9932185
TI  - Changes of biochemical markers during fracture healing.
AB  - The aim of this study was to evaluate the changes of biochemical markers during
      fracture healing in patients with osteoporosis. The study included 26 patients; 9
      underwent hip hemiarthroplasty (mean age +/- SD: 71.0 +/- 10.2 years, group EN)
      for femoral neck fractures. 7 underwent osteosynthesis (75.3 +/- 8.2 years, group
      OS) for trochanteric fractures, and 10 subjects had spinal compression fractures
      (68.2 +/- 12.0 years, group CO). No operative procedures were performed in group
      CO. Urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) by high performance
      liquid chromatography (HPLC), Crosslaps by both enzyme-linked immunosorbent assay
      (ELISA) and radioimmunoassay (RIA) (CTx-ELISA and CTx-RIA) and serum N-terminal
      mid-fragment osteocalcin (OCN-Mid) by ELISA were analyzed at the time of
      admission and at weeks 1, 2, 4, 8 and 24 after operation or, in the case of group
      CO, after admission. As a whole, bone resorption markers started to increase from
      week 1, with various peak values between weeks 4 and 8 depending upon the
      particular marker, but returned to the initial vales at week 24. OCN-Mid started
      to increase from week 8 and remained at elevated levels at week 24. In groups EN
      and OS, bone resorption markers changed in the same manner as they did as a whole
      group. OCN-Mid did not change in group EN, although it increased significantly
      from week 8 in group OS. No biochemical markers changed significantly in group
      CO. In conclusion, bone resorption was accelerated at an early stage due to acute
      osteonecrosis or bed rest, followed by bone formation due to callus or mechanical
      stress later on. As far as bone resorption markers are concerned, 24 weeks are
      enough to eliminate the effect of fracture.

PMID- 9932186
TI  - Measurement of skeletal flow with positron emission tomography and 18F-fluoride
      in femoral head osteonecrosis.
AB  - Positron emission tomography (PET) with 18F-fluoride was utilized to determine
      the regional blood flow to the femoral head in early osteonecrosis. Five patients
      with a history of unilateral hip trauma and a normal contralateral side were
      selected. Skeletal flow and fluoride uptake in the abnormal and normal hips were
      compared directly, and the relation between bone blood flow and final outcome,
      i.e., surgical replacement or conservative treatment, was evaluated. In this
      pilot study, a flow ratio of at least 2 between the abnormal and normal femoral
      head was necessary to predict a successful outcome with a conservative regimen. A
      minimum flow of 0.04 ml/min/ml was measured in one patient whose affected femoral
      head healed conservatively. Our preliminary study indicates that this type of
      highly technical investigation appears feasible in clinical practice and permits
      prediction of the outcome depending upon regional skeletal flow measurements in
      vivo.

PMID- 9932187
TI  - High complication rate of reconstruction using Ilizarov bone transport method in
      patients with bone sarcomas.
AB  - We performed five reconstructions by bone transport in patients with bone
      sarcoma: three osteosarcomas, one Ewing's sarcoma and one chondrosarcoma. Four
      sarcomas were in the distal femur and one in the shaft of the tibia. Four
      patients received multidrug chemotherapy. The average length of the skeletal
      defect after tumour resection was 17 (range 10-25) cm. All patients underwent
      double elongation from both proximal and distal sites of the bone defect. The
      average follow-up period was 48 (range 40-66) months, and the average duration of
      external fixation was 32 months (range 579-1340 days). In one case, bone
      formation was satisfactory, but in the other cases, it was poor and slow. The
      average treatment index was 95 (range 53-191) days per 1 cm of elongation. In one
      case, the bone fragment disappeared during the bone transport. In one case, the
      end of the bone protruded from the skin, and osteomyelitis set in. This patient
      underwent above-knee amputation due to failure of infection control. Three
      patients suffered talipes equinus. One patient died of pulmonary metastasis. Two
      patients had fair and three had poor function. This method is not recommended for
      patients with bone sarcoma who may have a poor prognosis, as it has an
      unacceptably high complication rate.

PMID- 9932188
TI  - Degradation of and intraosseous reactions to biodegradable poly-L-lactide screws:
      a study in minipigs.
AB  - In 20 minipigs an osteotomy of the lumbar spine was done at L3 and fixed with
      resorbable implants (plate and screws) made of poly-L-lactide. For 24 months
      postoperatively the cancellous bone surrounding the screws was examined
      histologically. Specimens from the body of lumbar spine L2 and L4, carrying the
      screws, were fixed in a series of ethanol immersions and then embedded in
      methylmethacrylate. Longitudinal and transverse sections were cut with a
      microtome at 4-5 microns and stained by the Masson-Goldner and Giemsa method for
      light microscopy. Our investigation confirmed a long degradation period of poly-L
      lactide and little inflammatory reaction within the bone during the whole period
      of observation. For poly-L-lactide the degradation time exceeded the longest
      follow-up time in this study, 24 months. Polymorphonuclear granulocytes and
      mononuclear round cells were scarce in all follow-up groups. Osteolytic changes
      or the emergence of seroma was not observed. Textured bone was evident early
      close to a thin fibrous capsule surrounding the screws. The remodelling of the
      bone close to the screws ensues by the formation of osteons.

PMID- 9932189
TI  - Preservation of anterior cruciate ligament in total knee arthroplasty.
AB  - Few prostheses allow preservation of the anterior cruciate ligament (ACL) during
      total knee replacement. We report a short-term, prospective, open study of 32 ACL
      retaining and 93 ACL-replacing total knee replacements and compare the respective
      outcomes of both prosthesis types with a follow-up time of 2-3 years. Mean
      operative time, complication or revision rates did not differ, nor did the early
      and late clinical and radiological evaluations. This study does not support the
      suggestion that technical difficulties increase for ACL preservation. The
      clinical and functional results were neither improved nor worsened for ACL
      retaining prostheses. There is thus no advantage, but also no inconvenience, in
      retaining the ACL according to short- to mid-term results of a gliding posterior
      cruciate ligament (PCL)-retaining prosthesis with ACL-replacement design. The
      possibility of an improved long-term outcome of an ACL-retaining prosthesis
      should be investigated further.

PMID- 9932190
TI  - Tissue response to bioabsorbable self-reinforced polylevolactide and
      polyglycolide pins implanted intra-articularly and directly into the bone on
      different levels. An experimental study on rats.
AB  - Self-reinforced poly-L-lactide (SR-PLLA) and self-reinforced polyglycolide (SR
      PGA) pins were implanted intra-articularly and directly into the bone of the
      distal femur of rats at three levels: above, on the same level, and under the
      surface. For the controls only channels were drilled, or the controls were not
      operated at all. The follow-up times were 3, 6, and 12 weeks for SR-PGA and 3, 6,
      12, and 24 weeks for SR-PLLA. The macroscopic appearance and histologically the
      villus reaction, the mononuclear phagocytosis and giant cells, the neutrophils,
      the lymphocytes, the plasma cells, the eosinophils, and the mast cells were
      analyzed. In the histologic analysis, the most favorable implantation depth was
      found to be under the surface where the contact between the implants and bone was
      best, and the orifice was covered with new trabecular bone at 3 weeks. This was
      especially seen in intra-articular implantation. In general, the tissue responses
      were mild, and could also be explained in the statistical analysis by a normal
      postoperative tissue response and faster biodegradation of PGA.

PMID- 9932191
TI  - Bone allograft contamination in multiorgan and tissue donors.
AB  - Multiorgan and tissue donors offer a larger quantity and high quality of bone
      allograft that cannot be obtained from living donors. The risk of bone
      contamination must be borne in mind if secondary sterilization is not performed.
      The bacteriological cultures of 270 bone segments obtained from 53 multiorgan or
      tissue donors were analysed to study the relationship between previous organ and
      tissue procurements and bone retrieval contamination. We concluded that no
      significant differences in bacterial contamination percentage were found for each
      type of previous organ and tissue procurement, nor in the number of teams per
      donor.

PMID- 9932192
TI  - Proprioception of the cruciate ligaments: receptor mapping in an animal model.
AB  - Ten anterior and posterior cruciate ligaments (ACL and PCL) harvested from adult
      sheep were investigated under light microscopy for data on the frequency and
      localisation of neural structures. Serial sections of 25 microns thickness were
      stained with a modified gold chloride technique. Receptors were classified
      according to their histological structure. Topographic distribution and frequency
      within the ligament texture were determined with the help of computerized image
      analysis. Three distinct neural structures could be identified: Ruffini endings,
      Ruffini corpuscles of the Golgi tendon organ-like type and Pacinian corpuscles.
      Golgi tendon organs were not found. In total, 274 and 238 neural structures were
      present in the 10 ACL and 10 PCL, respectively. Pacinian receptors were the most
      common structures, with a mean frequency of 13.6 +/- 5.3 (ACL) and 12.4 +/- 5.1
      (PCL), followed by Ruffini endings with 8.9 +/- 3.2 (ACL) and 7.8 +/- 2.9 (PCL),
      whereas Ruffini corpuscles had the lowest frequency with a mean value of 4.9 +/-
      2.1 (ACL) and 3.4 +/- 1.1 (PCL). The majority of the neural structures were
      located in the subsynovial sheath or closely associated with endotenon
      structures. The tibial and femoral insertion areas had a significantly increased
      receptor density compared with the midpart of the ACL and PCL (P < 0.001), where
      only 19.3% and 23.7% of the receptors were located. These results emphasise the
      complex sensory structure of the cruciate ligaments and provide a valid
      morphological basis for further neurophysiological investigations.

PMID- 9932194
TI  - Necrotising fasciitis-cryptogenic infection following posttraumatic immunopathy?
AB  - Even in the era of broad-spectrum antibiotics, necrotising fasciitis is still a
      life-threatening disease. It occurs not only after direct skin laceration but
      also in contused areas with secondary hematogenic infection. Early diagnosis and
      immediate surgical intervention are imperative to improve the survival rate. This
      disease often leads to secondary multiorgan, (particularly renal) failure. A
      pathophysiological pathway based on an immunological disorder of the host is
      presented in relation to a case report.

PMID- 9932193
TI  - Bilateral pathological femoral neck fractures secondary to ectopic parathyroid
      adenoma.
AB  - A rare case of bilateral pathological femoral neck fractures secondary to ectopic
      parathyroid adenoma is reported. Both hip fractures were treated with closed
      reduction and internal fixation. The right hip fracture healed uneventfully,
      whereas the left hip fracture developed non-union that required subtrochanteric
      osteotomy and internal fixation and eventually healed. Neither hip developed
      avascular necrosis.

PMID- 9932195
TI  - Extraskeletal Ewing's sarcoma mimicking traumatic hematoma.
AB  - We describe the clinical course of a 16-year-old baseball player with a history
      of recurrent hematoma of the thigh. The lesion was aspirated percutaneously
      several times and curetted under the diagnosis of traumatic hematoma.
      Microscopical examination revealed massive hemorrhage, necrosis, and a small
      number of Ewing's sarcoma cells. He died of multiple metastases. With recurrent
      hematoma in the soft tissue, neoplastic lesions should be ruled out.

PMID- 9932196
TI  - Intraosseous fat necrosis simulating septic arthritis and osteomyelitis in a
      patient with chronic pancreatitis.
AB  - A woman with a 20-year history of alcohol abuse and chronic pancreatitis
      developed an osteoarticular involvement of her right ankle in association with
      subcutaneous nodules. Histopathological examination of the tissue samples
      obtained during surgical revision of the ankle showed necrotic fat and connective
      tissue. Microbiological cultures remained negative. The patient was administered
      long-term antimicrobial treatment without any apparent benefit. Four months
      later, she died of pancreatic insufficiency and pneumonia. Postmortem examination
      showed numerous foci of intra-abdominal fat necrosis. Histopathological
      examination of the bone samples from the right ankle showed fat necrosis with
      lipophages. Based on these findings, we consider that the osteoarticular
      involvement in this patient was caused by intraosseous fat necrosis. This case
      reminds us of the importance of considering the possibility of this condition
      whenever a patient with chronic pancreatic disease develops sterile
      osteoarthritis.

PMID- 9932197
TI  - Irreducible Galeazzi injury.
AB  - We present a case of a Galeazzi-type of fracture dislocation with an irreducible
      distal radioulnar joint. This is illustrated by intraoperative pictures which may
      assist others who find themselves faced with this injury.

PMID- 9932198
TI  - Asymmetric bilateral traumatic hip dislocation.
AB  - A case of a patient with traumatic, simultaneous right posterior and left
      anterior hip dislocations without associated fractures is reported. Simultaneous
      asymmetric bilateral hip dislocation is very rare. The mechanism of this injury
      is discussed.

PMID- 9932199
TI  - The beast in the mosquito: the correspondence of Ronald Ross and Patrick Manson.

PMID- 9932200
TI  - Pacing therapy for congestive heart failure: is it ready for prime time?

PMID- 9932201
TI  - The role of oral 1C antiarrhythmic drugs in terminating atrial fibrillation.
AB  - Antiarrhythmic drug therapy still remains the mainstay in the management of many
      supraventricular and ventricular arrhythmias. Several studies have recently
      pointed out the role of orally administered class 1C drugs in terminating atrial
      fibrillation. These drugs can play an important role in the ambulatory management
      of selected patients. The electrophysiologic mechanisms of these antiarrhythmic
      drugs together with their pharmacologic properties and clinical indications are
      discussed according to the current literature.

PMID- 9932202
TI  - Technologic advances in implantable cardioverter defibrillators.
AB  - Multiple technologic advances in the implantable cardioverter defibrillator (ICD)
      have resulted in smaller size, easier implantation, and improved detection,
      therapy, and stored diagnostic information. Advanced dual-chamber ICDs are
      currently available that allow dual-chamber rate-responsive pacing with mode
      switching, enhanced detection algorithms, antitachycardia pacing, low-energy
      cardioversion, high-energy shocks, and extensive diagnostics. Based on
      improvements in lead systems and improved energy waveforms, almost all devices
      are being implanted with nonthoracotomy leads in the pectoralis area. The results
      of recent clinical trials have expanded indications for the ICD for primary and
      secondary prevention of sudden cardiac death. With advances in capacitor and
      battery technology coupled with improved lead systems and waveform resulting in
      lower defibrillation thresholds, it is likely that lower-output, smaller devices
      will be developed. In the future, ICDs may have expanded indications and may
      incorporate physiologic sensors to access hemodynamic significance of arrhythmias
      and algorithms for prediction and prevention of cardiac arrhythmias.

PMID- 9932203
TI  - New advances in class III antiarrhythmic drug therapy.
AB  - During the past 10 years there has been a major shift in antiarrhythmic drug
      development from class I to class III antiarrhythmic agents. The first two class
      III antiarrhythmic drugs that became available, sotalol and amiodarone, also have
      potent antiadrenergic actions. Newer antiarrhythmic drugs either block a specific
      ionic current (e.g., dofetilide-induced blockade of the rapidly activating
      component of the delayed rectifier potassium current) or block multiple ionic
      channels (e.g., ibutilide and azimilide) in order to prolong atrial and
      ventricular action potentials without other specific pharmacologic effects.
      Recent data suggest that these new class III antiarrhythmic drugs are highly
      effective for treating patients with rhythm disorders with an acceptable degree
      of proarrhythmia. This manuscript reviews the newer class III agents'
      effectiveness in treating atrial and ventricular arrhythmias and the recent
      studies examining drug-induced prolongation of atrial repolarization to prevent
      or terminate postoperative atrial fibrillation.

PMID- 9932204
TI  - Cardiac arrhythmias and the athlete.
AB  - Athletes, although the healthiest segment of society, can develop cardiac
      arrhythmias. Benign bradycardias and atrial and ventricular premature
      contractions are common and seldom require treatment. Supraventricular
      tachycardias are less common and are usually not life-threatening, but do require
      treatment. Ventricular arrhythmias, although uncommon, are life-threatening and
      require treatment. Most athletes with ventricular arrhythmias have structural
      cardiac abnormalities, and further competitive play is usually prohibited.
      Commotio cordis, which is a recently described syndrome of sudden death caused by
      low-energy chest wall impact, may account for a significant percentage of the
      sudden deaths in athletes.

PMID- 9932206
TI  - Arrhythmias and women.
AB  - The incidence and risk factors for a variety of arrhythmias differ among men and
      women. Although symptomatic atrial reentrant tachycardias have a female
      predominance, the reverse is true for atrial fibrillation. Women have a lower
      incidence of sudden death. On the other hand, drug-induced torsades de pointes
      and symptomatic long QT syndrome have a female predominance. The incidence of
      arrhythmias seem to be increased during pregnancy. The mechanisms of these gender
      differences are unclear but may be related to hormonal effects and the shorter QT
      interval in men. Pharmacologic and nonpharmacologic therapy are equally
      efficacious in men and women.

PMID- 9932205
TI  - Radiofrequency catheter ablation for postinfarct ventricular tachycardia.
AB  - Catheter mapping and radiofrequency ablation of postinfarct sustained ventricular
      tachycardia (VT) remain one of the greatest challenges for the
      electrophysiologist. Although there were no major breakthroughs during the past
      year, several refinements and clarifications of existing mapping criteria were
      published. In addition, initial reports appeared describing new mapping systems
      and ablation technologies that may significantly impact the way ablation studies
      are performed as well as the way in which they affect success rates.
      Uncertainties remain as to how effective catheter ablation will be as a longterm
      cure for this type of VT. For the foreseeable future, catheter ablation in
      postinfarct VT will remain adjunctive rather than primary therapy.

PMID- 9932207
TI  - Extraction of pacemaker and implantable cardioverter defibrillator leads.
AB  - The common reasons for removal of pacing and defibrillator leads are infection,
      malfunction, or design defects such as fracture of J wires in Teletronics Accufix
      leads (Telectronics Pacing, Englewood, CO), which impose considerable risk for
      cardiac morbidity and mortality. Chronically implanted leads are fixed to the
      myocardium by fibrous tissue. Fibrous scar tissue may also encase the lead along
      its course. Furthermore, fragility of the lead and its tendency to break when
      extraction force is applied to overcome resistance imparted by the scar tissue
      add to the challenge of lead extraction. Thus, the extraction of chronically
      implanted leads is an important issue. Until a few years ago, the only methods
      available for the removal of chronically implanted leads were traction on the
      proximal segment of the lead and cardiac surgery. New techniques were developed
      to extract the leads by a transvenous approach using locking stylets, sheaths,
      snares, and retrieval baskets. Lead extraction using intravascular
      countertraction methods has since evolved as a specialty of its own. Progress has
      also been made in developing other system, such as Excimer laser energy for lead
      extraction. In this article, we discuss principles, techniques, and experience
      with these methods of extraction of chronic pacemaker and defibrillator leads.

PMID- 9932208
TI  - Three-dimensional echocardiography in congenital heart disease.
AB  - Recent advances in transducer technology and image processing have led to the
      development of two techniques for three-dimensional (3-D) echocardiography: 1) 3
      D reconstruction and 2) real-time 3-D (RT3-D) volumetric imaging. 3-D
      reconstruction creates a 3-D data set from a series of two-dimensional (2-D)
      images. RT3-D echocardiography uses a 2-D matrix phased array transducer with
      multiple parallel processing to produce real-time volumetric images of the heart.
      Both technologies produce novel views of congenital heart defects and offer
      improved quantification of ventricular volume, mass, and function. The main
      advantage of RT3-D imaging is its ability to capture 3-D data in real time. This
      avoids the motion artifact inherent with any reconstructive technique and permits
      analysis of events during a single cardiac cycle; however, at present, RT3-D
      imaging has poorer image quality and lacks the Doppler capability. Further
      development in both techniques will allow 3-D echocardiography to have more
      widespread clinical applicability.

PMID- 9932209
TI  - Evaluation and management of pulmonary atresia with intact ventricular septum.
AB  - Pulmonary atresia with intact ventricular septum (PA/IVS) is a spectrum of
      diseases with varying severity of right ventricle hypoplasia and potential for
      biventricular, univentricular, or hybrid repairs. Pessimistic outcome measures
      for PA/IVS may give way to optimism with the refinement of early diagnosis and
      early intervention to encourage right ventricle flow and optimize growth. To this
      end, PA/IVS has become a focus of innovative interventions (e.g., fetal surgery)
      and new catheter-based and surgical techniques.

PMID- 9932210
TI  - Minimally invasive pediatric cardiac surgery.
AB  - Minimally invasive cardiac surgery has evolved in response to the intrinsic irony
      facing cardiac surgeons: that we must injure our patients to treat them. In
      recent years, advances in fiberoptic imaging technology, applied to other
      surgical specialties, suggested the possibility that cardiac surgery might also
      be performed endoscopically. The anatomic and spatial constraints of pediatric
      cardiac surgery, and its dependence on extreme levels of speed, precision, and
      three-dimensional perception, made the application of remote, two-dimensional
      operating systems seem impossible, or at least imprudent in this special group of
      patients. Despite these limitations, however, applications of video-assisted
      endoscopic surgical techniques have been demonstrated to allow the safe and
      effective performance of an expanding range of operative procedures in congenital
      heart surgery. The guided development of new technology will accelerate this
      process in the coming years.

PMID- 9932211
TI  - Recent advances in interventional pediatric cardiovascular disease.
AB  - Transcatheter therapy in children with congenital or acquired heart disease is a
      challenging, innovative, and constantly evolving field. In this article we review
      the various "nonsurgical" techniques that are currently available, with a
      discussion of their applications and an update on the recent advances in the
      field of interventional cardiology.

PMID- 9932213
TI  - Bibliography. Current world literature. Coronary artery surgery.

PMID- 9932212
TI  - Bibliography. Current world literature. Imaging and echocardiography.

PMID- 9932214
TI  - Molecular basis of insulin action.
AB  - Considerable progress has been made in our understanding of the molecular
      mechanisms of insulin action. The insulin receptor is a membrane receptor
      possessing tyrosine kinase activity. The binding of insulin to its receptor
      induces autophosphorylation of the receptor on tyrosine residues and thereby
      stimulates its tyrosine kinase activity towards intracellular substrates such as
      Shc or IRS1. This tyrosine kinase activity, which plays a crucial role in the
      transmission of the signal, is decreased in several insulin-resistance
      situations. This decrease was initially attributed to the phosphorylation of the
      receptor on serine or threonine residues, but this mechanism is now seriously
      questioned. Tyrosine phosphorylation of IRSs and Shc by the insulin receptor
      permits the activation of two major signalling pathways, the MAP kinase pathway
      and the Pl 3-kinase pathway. MAP kinases are involved in proliferation and
      differentiation processes, in particular by regulating the transcriptional
      activity of the nucleus. The MAP kinase pathway does not appear to play a
      significant role in the transmission of the metabolic effects of insulin. In
      contrast, the Pl 3-kinase pathway is involved in several of the metabolic effects
      of the hormone, such as glucose transport, glycolysis and glycogen synthesis. The
      Pl 3-kinase pathway also plays a crucial role in the regulation of protein
      synthesis by insulin. Moreover, this pathway is involved in cell growth and
      transmits a strong anti-apoptotic signal.

PMID- 9932215
TI  - Role of apolipoprotein CIII in triglyceride-rich lipoprotein metabolism.
AB  - Apolipoprotein CIII (ApoCIII) appears to play a key role in triglyceride-rich
      lipoprotein (TRL) metabolism. This 8.8 kDa polypeptide is mainly synthesized by
      the liver in 3 isoforms. The gene involved has been mapped on chromosome 11, and
      several polymorphisms associated with hypertriglyceridaemia and/or coronary
      artery disease (CAD) have been described. In normolipidaemic individuals, the
      total plasma ApoCIII level (0.10 g/l) is mainly HDL-linked. Plasma levels are
      increased in hyper-triglyceridaemic subjects in whom ApoCIII is VLDL-linked. In
      Type 2 diabetic patients, the ApoCIII concentration varies with metabolic control
      of the disease but does not always correlate with the triglyceride level. In
      various clinical studies, the level of VLDL/LDL-linked ApoCIII was correlated
      with the severity of the CAD score, and treatment with fibrates decreased the
      ApoCIII mRNA level in association with PPAR activation. Overexpression of the
      human ApoCIII gene in transgenic animals results in hypertriglyceridaemia, which
      can be corrected by overexpression of the ApoE gene. ApoCIII decreases TRL
      catabolism by inhibiting lipoprotein lipase activity and reducing ApoE-dependent
      hepatic uptake of TRL and remnants. There appears to be an interaction between
      ApoCIII and ApoE at the surface of the lipoprotein. Our recent study of ApoCIII
      levels in TRL and intermediate-density lipoprotein isolated from hyperlipidaemic
      Type III and IV individuals confirmed the importance of the ApoCIII/ApoE ratio in
      these lipoproteins.

PMID- 9932216
TI  - Should there be systematic screening of coronary heart disease in asymptomatic
      patients with risk factors alone? A decision analysis approach.
AB  - The problem of choosing between detection of asymptomatic coronary heart disease
      (CHD) in patients at risk and primary prevention was assessed in a decision
      analysis model. Most of the relevant data were derived from the WOSCOP study,
      which evaluated the effects of statins in asymptomatic hypercholesterolaemic
      subjects. This study is considered to be a model of primary prevention
      measurement. Over a 5-year period, 10% of control subjects had events related to
      CHD, with a 20% mortality rate which was reduced by 33% under statin
      administration. A decision tree was used to compare these two sets of data
      (controls and treated patients) with those of a third option in which an exercise
      test, 201Tl scintigraphy and, in certain cases, coronary arteriography were used
      to detect and treat CHD at an asymptomatic stage. The test characteristics and
      outcomes correspond as closely as possible to previously reported data,
      concerning what can be expected in this particular situation. Over a wide range
      of CHD probabilities, screening appeared to be better than primary prevention.
      This result is robust since it was not modified by sensitivity analysis for most
      of the data. A sharp decrease in the sensitivity of the first two tests and a
      marked increase in the effectiveness of primary prevention would alter the
      decision in favour of primary prevention, whereas an increased death rate from
      CHD and higher CHD probability would favour the utility of screening. As the cost
      effectiveness of screening compares favourably with that of primary prevention,
      it may be useful to assess the validity of this model in a prospective controlled
      study.

PMID- 9932217
TI  - Quality of diabetes care, diabetes knowledge and risk of severe hypoglycaemia one
      and four years after participation in a 5-day structured treatment and teaching
      programme for intensified insulin therapy.
AB  - Intensification of insulin therapy in the Diabetes Control and Complications
      Trial led to an improvement in the quality of diabetes care, which was
      accompanied, however, by a threefold increase in the risk of severe
      hypoglycaemia. The present trial, a long-term evaluation of a structured 5-day
      treatment and teaching programme (DTTP) for intensified insulin therapy, was
      performed to clarify factors determining HbA1c, the incidence of severe
      hypoglycaemia, diabetes knowledge and quality of life. Ninety-four Type 1
      diabetic patients were examined at baseline and 4 years after participation in a
      DTTP. Comparison of baseline data with measurements at the 4-year follow-up
      examination showed that relative HbA1c (= HbA1c/mean normal) improved (1.9 +/-
      0.51 vs 1.55 +/- 0.3*, p < 0.001, *excluding 4 patients with diabetes
      manifestation at baseline) and that frequencies of daily insulin injections (3.73
      +/- 1.23 vs 4.9 +/- 0.69*, p < 0.001) and weekly blood glucose self-tests (6.6 +/
      10.1 vs 25.5 +/- 8.7*, p < 0.001) increased, whereas the incidence of severe
      hypoglycaemia (intravenous glucose, glucagon injection) remained stable (0.19 vs
      0.24, p = 0.48). Patients with less diabetes knowledge had higher HbA1c levels
      and a higher incidence of severe hypoglycaemia. In the group of patients with
      severe hypoglycaemia, certain crucial gaps in diabetes knowledge were identified
      concerning the effects of physical activity, nutrition and long-term
      complications of diabetes. In multivariate analysis. The most important factor
      associated with HbA1c was diabetes knowledge which, however, was not influenced
      by educational level or other factors. Interventions, such as the identification
      of psychosocial factors which may interact with diabetes knowledge, quality of
      life and successful self-management of diabetes by patients, are needed to
      improve the efficacy of DTTPs and to prevent severe side effects such as
      hypoglycaemia.

PMID- 9932218
TI  - Long-term culture of free or encapsulated islets isolated from specific pathogen
      free (SPF) pigs.
AB  - As the risk of recipient contamination is a limiting factor for
      xenotransplantation, the use of specific pathogen-free (SPF) pigs is mandatory.
      This study investigated the long-term culture of SPF pig islets and evaluated
      their insulin production when encapsulated in AN69 hollow fibres. Insulin
      secretion was studied after 3 weeks (n = 10), 2 months (n = 8) and 3 months (n =
      3) by 45-min incubation in the presence of 2.8, 5.5, 11 and 16.5mM glucose.
      Although a decrease in the amount of secreted insulin occurred (1385 +/- 421 and
      4323 +/- 1068 microns U/ml at 3 weeks for 2.8 and 16.5 mM glucose respectively;
      702 +/- 261 and 2397 +/- 1047 microU/ml at 2 months; 59 +/- 23 and 154 +/- 34
      microU/ml at 3 months), glucose-dependent insulin secretion was observed in all
      cases, i.e. stimulation indices of 8.1 +/- 3.1 (p < 0.05 vs the presence of 5.5
      mM glucose) at 3 weeks, 3.3 +/- 1.1 at 2 months and 3.0 +/- 0.7 at 3 months. The
      insulin secretion of encapsulated SPF pig islets, cultured for 1 or 3 weeks, was
      evaluated under perifusion conditions using a stimulus of 10mM glucose plus 5.5
      mM theophylline. Glucose stimulation resulted in a significant two-fold increase
      in insulin secretion (p < 0.05), which was maintained over culture time. These
      results indicate that SPF-isolated islets remained functional when cultured for
      several weeks either as free or encapsulated islets, although the magnitude of
      insulin secretion decreased dramatically after three months of culture.

PMID- 9932219
TI  - Effects of regular insulin or insulin LISPRO on glucose metabolism after an oral
      glucose load in patients with type 2 diabetes mellitus.
AB  - Seven obese Type 2 diabetic patients were studied for two 4-h periods after
      ingestion of a glucose load to determine the effects of preprandial subcutaneous
      injection of Insulin Lispro (5 min before the meal) or regular insulin (20 min
      before the meal) on glucose metabolism. Glucose production and utilisation were
      measured using a dual isotope method. After Lispro, the mean postprandial
      increase in plasma glucose was 29% lower and the increase in insulin
      concentration 25% higher than after regular insulin (p < 0.05). Suppression of
      endogenous glucose production was similar with both types of insulin. Thus,
      preprandial injection of Lispro reduced postprandial glucose increments in Type 2
      diabetic patients as compared to regular insulin. This effect is best explained
      by the increased postprandial bioavailability of Lispro.

PMID- 9932220
TI  - Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial
      overgrowth.
AB  - The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are
      multifactorial and complex, although small intestinal bacterial overgrowth and
      autonomic neuropathy seem to play a major role. This study evaluated the
      prevalence of small intestinal bacterial overgrowth and the effects of antibiotic
      treatment in a population of diabetic patients with chronic diarrhoea (defined as
      > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal
      bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing
      (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration,
      number of stools per day, and gastrointestinal symptoms) were noted. Autonomic
      neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients
      were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group
      1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/-
      11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS),
      and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the
      two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75
      +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/-
      2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P <
      0.05). The prevalence of small intestinal bacterial overgrowth syndrome and
      gastrointestinal symptoms was not different in patients with and without
      autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients
      with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5
      g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of
      these patients. It is concluded that small intestinal bacterial overgrowth should
      be considered in case of chronic diabetic diarrhoea because of its frequency
      (43%), facility of diagnosis, and often successful treatment with antibiotics.

PMID- 9932221
TI  - Prevalence of diabetes mellitus and associated risk factors in an adult urban
      population in Shanghai.
AB  - A cross-sectional study was conducted in an urban population 25 years of age and
      older to determine the prevalence of diabetes mellitus (DM), impaired glucose
      tolerance (IGT), and associated risk factors. A total of 13,940 subjects was
      surveyed (7,042 male, 6,898 female). The prevalence (DM 2.33%, IGT 1.30) was much
      higher than in a 1978 study. Age-standardised prevalence was not statistically
      different between males and females: respectively 2.54% and 2.14% for DM and
      1.42% and 1.31% for IGT. Most diabetic patients were well-educated and performed
      mildly intensive labour. More patients showed a family history of diabetes during
      youth and risk factors associated with diabetes in old age, e.g. hypertension and
      an overweight condition. Microalbuminuria was found in 20.26% of newly diagnosed
      diabetic patients, i.e. a much higher proportion than in the normal population.

PMID- 9932222
TI  - Lipoatrophic diabetes mellitus treated by continuous subcutaneous insulin
      infusion.
AB  - This case report evaluated continuous subcutaneous insulin infusion (CSII) in a
      50-year-old Caucasian woman who suffered from partial lipodystrophy and severely
      insulin-resistant diabetes mellitus. Intensive insulin therapy (three daily
      injections) failed to provide good metabolic control (HbA1c ranging from 10 to
      12%). Even though the patient had very thin subcutaneous tissue, CSII was
      initiated and proved highly efficient, improving blood glucose control
      considerably (HbA1c ranging from 7.5 to 8.5%), but with no decrease in the daily
      insulin requirement (2 IU/kg/day). Plasma triglycerides were also greatly
      improved (from 16.5 to 3.7 mmol/l). Thus, this study indicates that CSII is
      suitable for patients with lipoatrophy and insulin-resistant diabetes mellitus.

PMID- 9932223
TI  - Protease inhibitors, diabetes mellitus and blood lipids.
AB  - We report the case of a patient with human immunodeficiency virus (HIV) and no
      familial or personal history of metabolic disease, who experienced two diabetes
      decompensations (severe hyperglycaemia without ketonuria) associated with severe
      hypertriglyceridaemia, after the introduction of protease inhibitors. Initial
      insulin therapy at high doses (2 IU/kg/day) was required, and metabolic control
      was restored within several weeks without treatment after withdrawal of protease
      inhibitors. This case confirms that due attention must be paid to both blood
      glucose and plasma triglyceride levels in HIV-infected patients treated with
      protease inhibitors.

PMID- 9932224
TI  - Appraisal and implications of predictive testing for insulin-dependent diabetes
      mellitus.
AB  - The risk of developing insulin-dependent diabetes mellitus (IDDM) is 50 times
      greater in first-degree relatives than in the general population. Although
      parents of a diabetic child are generally aware of the risk of disease recurrence
      in the family, the practice of screening for IDDM is often questioned by
      physicians themselves because of the likelihood that parents will experience
      anxiety. This paper reports the results of a questionnaire distributed to parents
      attending a pediatric clinic for their diabetic child who were asked to evaluate
      their attitudes about screening tests. One hundred and thirty-one families
      recruited over a 2-month period replied to the questionnaire without the
      assistance of medical staff. The mean age of diabetic children was 10 +/- 4.05
      years, and the duration of IDDM 3 +/- 3.6 years. The results show that parents
      were stressed by the possible development of a second case of IDDM among their
      children. Eighty percent of them practised home strip--analysis on a regular
      basis for all their children. The parents wanted biological tests to be performed
      on their children before the occurrence of any clinical symptoms. They expected
      the screening tests "to reveal the truth about the health status of their
      children" (92%) and to "help prepare for an uncertain future" (60%). They
      indicated that recognition of an increased risk would not change their attitude
      toward their child. Recurrence of the disease was regarded as a problem with
      which the parents could cope realistically. Our data indicate that parents should
      continue to be informed about familial risk and the possibility of screening,
      despite the lack of preventive treatment.

PMID- 9932225
TI  - Five-year follow-up of daily glycaemia in a subject with insulin-dependent
      diabetes mellitus.

PMID- 9932226
TI  - [So-called "functional" insulin therapy].

PMID- 9932227
TI  - Translational control elements in the major human transforming growth factor-beta
      1 mRNA.
AB  - Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta
      1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in
      vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently
      translated. The contribution of the 5'- and 3'-untranslated regions (UTRs) to the
      translational inhibition of the full-length TGF-beta 1 transcript was studied by
      deletion analysis. Despite their high G + C content, both UTRs stimulated
      translation in vitro. However, polysome analysis of synthetic TGF-beta 1 mRNAs
      transfected into MCF-7 cells suggests that the cell contains a limited pool of
      trans-acting factors that interact with the 5'UTR to make it inhibitory in vivo.
      Further deletion analysis in vitro revealed multiple stimulatory and inhibitory
      regions in the 5'UTR. This has important implications for the translatability of
      the naturally occurring shorter TGF-beta 1 transcripts and provides a framework
      for higher resolution mapping studies. Overall, the poor translational efficiency
      of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor
      initiation sequence context, and inhibitory interactions of limiting transacting
      factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR.

PMID- 9932228
TI  - Transforming growth factor beta 1 and its receptor types I and II. Comparison in
      human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.
AB  - An immunohistochemical and semiquantitative comparative study of transforming
      growth factor beta 1 (TGF-beta 1) and its receptor types I (TGF-beta RI) and II
      (TGF-beta RII) was carried out in normal prostates and in the prostates from men
      with benign prostatic hyperplasia (BPH), and men with prostatic adenocarcinoma.
      Immunoreaction to TGF-beta 1 was limited to the basal epithelial cells in the
      normal prostates. Some cells in the connective tissue stroma were also stained.
      In BPH immunolabelling was also observed in columnar (secretory) cells of the
      epithelium. In prostatic adenocarcinoma, all epithelial cell types were intensely
      immunostained. Some stromal cells were also stained. Immunostaining to TGF-beta
      RI was only present in the basal cells in normal prostates. In BPH, this
      immunoreaction was found in the whole epithelium and in some stromal cells. In
      prostatic cancer, the immunostaining pattern for this receptor was similar to
      that of BPH but more intense in the epithelial cells. Immunoreactivity to TGF
      beta RII appeared in some basal cells and some scattered columnar cells of the
      normal prostate epithelium. In the BPH sections, this pattern was maintained, and
      a weak immunolabelling was also observed in the stroma. In prostate cancer, all
      epithelial cells appeared intensely labelled. In the stroma, immunolabelling was
      similar to that of the BPH specimens. The results of the present study suggest
      that, in normal prostates, only the basal cells of the epithelium possess both
      receptor types, and hence can transduce TGF-beta 1 signal intracellularly. The
      basal cells can also secrete this growth factor which would act as an autocrine
      inhibitory growth factor for them. In addition, TGF-beta 1 is secreted in some
      zones by stromal cells, acting then as a paracrine growth factor for basal cells
      in those areas. In BPH, in addition to the basal cells, some secretory columnar
      cells also secrete TGF-beta 1 and possess both types of TGF-beta 1 receptors, and
      thus, both epithelial cell types are susceptible to TGF-beta 1 action. Since both
      receptor types are also present in some stromal cells, these cells also perform
      an autocrine secretion, in addition to their paracrine secretion to the
      epithelial cells. TGF-beta RIIs seem to be more numerous than TGF-beta RIs and
      this lead us to hypothesize that these incomplete receptors might be a protection
      against the inhibition caused by TGF-beta 1 action. In prostatic carcinoma all
      cell types display the same characteristics as in BPH, although both receptor
      types are found in similar numbers, and thus, the above mentioned protection
      would not occur.

PMID- 9932229
TI  - Mutation of C-terminal tyrosine residues Y497/Y504 of the Src-family member
      Bsk/Iyk decreases NIH3T3 cell proliferation.
AB  - To elucidate the properties of the Src-family member Bsk/Iyk, NIH3T3 cells were
      transfected with wild-type Bsk/Iyk or Bsk/Iyk carrying Y497F, Y504F or Y497/504F
      mutations. These positions are putatively homologous to tyr-527 in Src. The
      Bsk/IykY497/504F cells displayed a decreased cell growth rate, parallelled by an
      augmentation of the fraction of cells in G1-phase. The Bsk/IykY497/504F double
      mutation decreased the [3H]thymidine incorporation. No effects on NIH3T3 cell
      growth could be seen in cells expressing wild-type Bsk/Iyk or the other Bsk/Iyk
      mutants. In vitro kinase reactions performed on immunoprecipitates from NIH3T3
      cells expressing wild-type or mutated Bsk/Iyk revealed increased relative [32P]
      incorporation into Bsk/Iyk isoforms containing the Y504F and Y497/504F mutations
      compared with wild-type Bsk/Iyk. The Y497F and Y497/504F mutations elevated the
      proportion of [32P]-incorporation into a 57 kDa Bsk/Iyk product relative to that
      into the 60 kDa isoform. The Y497F Bsk/Iyk mutant not only increased the relative
      amount of p57 Bsk/Iyk but also transferred this isoform to the nuclear
      subcellular fraction. The results suggest that Bsk/Iyk has unique regulatory
      properties, and that this kinase might serve a role in inhibiting cell
      replication.

PMID- 9932230
TI  - Fibroblast growth factor receptor (FGFR)-1 and -2 in the ovine corpus luteum
      throughout the estrous cycle.
AB  - Fibroblast growth factors (FGFs) probably play an important role in development
      and maintenance of the vasculature of the corpus luteum (CL). The objective of
      the present study was to evaluate the distribution and levels of fibroblast
      growth factor receptors (FGFRs) in the ovine CL from the early, mid- and late
      stages of the estrous cycle. Presence of FGFR-1 and -2 receptors was evaluated in
      CL by using Western analysis, immunohistochemistry and topical autoradiography.
      Western analysis demonstrated that the levels of FGFR-1 and -2 were similar in
      the early and mid-cycle CL but increased (p < 0.05) in the late stage of the
      estrous cycle. Immunohistochemistry and topical autoradiography demonstrate that
      both parenchymal (steroidogenic) and nonparenchymal (e.g. endothelial,
      fibroblastic) cells express FGFR-1 and -2. FGFR-1 was localized to the luteal
      vasculature throughout the estrous cycle; in the parenchymal cells, it was
      present during mid-cycle but was barely detectable in the late stage. Conversely,
      FGFR-2 was present in the parenchymal cells at all stages of the estrous cycle
      but localized to the larger microvessels only at the late stage. These data
      demonstrate that FGF receptors are present in the parenchyma as well as the
      vasculature of the CL which suggests that FGF is involved in the regulation of
      luteal parenchymal and vascular function.

PMID- 9932231
TI  - A novel type of regulatory element is required for promoter-specific activity of
      the PDGF-B intronic enhancer region.
AB  - We have previously described a non-classical, promoter-specific enhancer for the
      human Platelet-Derived Growth Factor B (PDGF-B) gene. In JEG-3 choriocarcinoma
      cells the activity of the enhancer depends upon co-operation with a sequence (the
      Enhancer-Dependent cis Co-activator "EDC" element) within the promoter. The PDGF
      B enhancer fails to activate heterologous promoters, indicating that promoter
      specificity depends on an element within the enhancer that can recognise a target
      sequence within the promoter. Here we identify a sequence within the enhancer of
      the PDGF-B gene which directs activation of the PDGF-B promoter by distal cis
      acting elements. This specifies the wild-type PDGF-B promoter as the target for
      the enhancer and has been designated the EDC specificity element (EDCse). The
      cell-type specific nature of this interaction is extended by the observation that
      the EDCse is also dispensable for enhancer activity in breast-cancer cells (ZR
      75). Concomitant to this observation, JEG-3 and ZR-75 cells differ in the binding
      of nuclear factors to the EDCse. We discuss the relevance of the EDC/EDCse system
      in regulation of gene expression.

PMID- 9932232
TI  - The international standard for platelet-derived growth factor-BB: comparison of
      candidate preparations by in vitro bioassays and immunoassays.
AB  - In an international collaborative study, four preparations of recombinant, human
      sequence, platelet-derived growth factor-BB (PDGF-BB), two glycosylated and two
      nonglycosylated, were evaluated, using in vitro bioassays and immunoassays, by
      seven laboratories in three countries, for their suitability to serve as the
      international standard (IS) for PDGF-BB. The study shows that interlaboratory
      variation in estimates of PDGF-BB potency is reduced by use of a common standard.
      The bioassays, using various types of fibroblast, detected PDGF-BB and PDGF-AB as
      equally potent, while immunoassays discriminated between the two isoforms. On the
      basis of the results reported here, the World Health Organization (WHO)
      established the preparation coded 94/728 as the first IS for PDGF-BB, with an
      assigned unitage of 3000 International Units per ampoule. The IS may be obtained
      by writing to NIBSC, PO Box 1193, Potters Bar, EN6 3QH, UK, or through web site
      http:??www.nibsc.ac.uk.

PMID- 9932233
TI  - Attentional capacities in children with autism: is there a general deficit in
      shifting focus?
AB  - Twenty-three children with autism and two control groups completed an attention
      battery comprising three versions of the continuous performance test (CPT), a
      digit cancellation task, the Wisconsin Card Sorting Test (WCST), and two novel,
      computerized tests of shifting attention (i.e., the Same-Different Computerized
      Task and the Computerized Matching Task). Children with autism could focus on a
      particular stimulus and sustain this focus as indicated by their performance on
      the digit cancellation task and the CPT. Their performance on the WCST suggested
      problems in some aspects of shifting attention (i.e., disengaging attention). The
      autism group performed as well as controls on the Same-Different Computerized
      Task, however, that required successive comparisons between stimuli. This implies
      that they could, in fact, shift their attention continuously. In addition, they
      did not differ from controls on the Computerized Matching Task, an analog of the
      WCST, suggesting that they do not have a general deficit in shifting attention.

PMID- 9932234
TI  - Children with autism fail to orient to naturally occurring social stimuli.
AB  - Children with autism were compared to developmentally matched children with Down
      syndrome or typical development in terms of their ability to visually orient to
      two social stimuli (name called, hands clapping) and two nonsocial stimuli
      (rattle, musical jack-in-the-box), and in terms of their ability to share
      attention (following another's gaze or point). It was found that, compared to
      children with Down syndrome or typical development, children with autism more
      frequently failed to orient to all stimuli, and that this failure was much more
      extreme for social stimuli. Children with autism who oriented to social stimuli
      took longer to do so compared to the other two groups of children. Children with
      autism also exhibited impairments in shared attention. Moreover, for both
      children with autism and Down syndrome, correlational analyses revealed a
      relation between shared attention performance and the ability to orient to social
      stimuli, but no relation between shared attention performance and the ability to
      orient to nonsocial stimuli. Results suggest that social orienting impairments
      may contribute to difficulties in shared attention found in autism.

PMID- 9932235
TI  - Spontaneous play in children with autism: a reappraisal.
AB  - Much controversy remains regarding the ability of children with autism to engage
      in spontaneous play. In this study children with autism, Down syndrome and
      typical development with verbal mental ages of approximately 2 years were
      assessed for play abilities at three data points. Even in this group of children
      with autism, who had relatively low verbal mental ages, symbolic play skills were
      not totally absent. However, it was possible to distinguish their pattern of play
      behaviors from the other two groups. Consequentially, it is argued that there are
      unusual features in early spontaneous play in children with autism and these
      atypical patterns are not restricted to their difficulties in the production of
      symbolic play. Such differences in early spontaneous play raise interesting
      questions about the etiology of autism, the direction of future research, and the
      theoretical models that can account for the condition.

PMID- 9932236
TI  - Autistic behavior in young boys with fragile X syndrome.
AB  - A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133
      months was rated using the Childhood Autism Rating Scale (CARS) to assess the
      extent to which autism and autistic features were evident in a young population.
      Fourteen subjects (approximately 25% of the sample) scored above the cutoff for
      autism, suggesting a relatively high incidence of autistic behavior. All but 2 of
      these 14 were in the mildly or moderately autistic range, however, and only a few
      items received severe ratings, suggesting that severe autism is relatively rare
      in fraX, at least during the early years. The CARS resulted in a continuum of
      autistic ratings in the fraX population, but no particular items on the CARS
      contributed disproportionately to autism ratings. A visual comparison of ratings
      on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting
      that differentiating fraX and autism on the basis of CARS ratings is not likely.
      Within the fraX group, chronological age and socioeconomic status did not
      correlate with CARS ratings, but severity of delay was strongly related, such
      that more severely delayed children scored higher (more autistic) on the CARS.

PMID- 9932237
TI  - Social functioning among girls with fragile X or Turner syndrome and their
      sisters.
AB  - Social behaviors among two genetically homogeneous groups--girls with fragile X
      (fraX) or Turner syndrome (TS)--were examined to address the role of family
      environment versus biological determinants of social dysfunction in girls with
      these disorders. Using a sibling pair design, girls with fraX or TS were compared
      with their own sisters on measures of IQ and social functioning. The 8 girls with
      fraX and the 9 girls with TS had lower FSIQ scores and higher ratings of social
      and attention problems relative to their own sisters. Girls with fraX also had
      higher ratings of withdrawn behaviors, relative to their own sisters. The
      unaffected sisters were not rated as demonstrating any difficulties in these
      areas, relative to controls. Correlations between problem ratings and FSIQ were
      not statistically significant. Although these preliminary findings do not
      indicate a lack of familial impact on social development in girls with either
      disorder, the results provide preliminary evidence that social dysfunction
      reported for girls with fraX or TS cannot be attributed solely, nor primarily, to
      global aspects of the family environment.

PMID- 9932238
TI  - The preserved speech variant: a subgroup of the Rett complex: a clinical report
      of 30 cases.
AB  - Thirty girls and young women, 6 from Sweden and 24 from Italy, are described in
      this paper. They ranged in age from 5 through 28 years. All but one of the cases
      met full symptom criteria for DSM-IV autistic disorder. However, they also showed
      many features of classic Rett syndrome (RS) as outlined by the Rett syndrome
      Diagnostic Criteria Work Group. All met the required 3 out of 6 main criteria and
      47% also met both these and the required 5 out of 11 supportive criteria for RS
      variants as outlined by Hagberg. The course of the disorder was more benign than
      in classic RS, but all the girls were severely functionally impaired. There was
      familial clustering in a subgroup. It is concluded that these 30 cases represent
      a syndrome, similar and probably related, to classic RS. It is suggested that
      there is a spectrum of syndromes ranging from severe cases with classical
      presentation to considerably milder variants. We propose that, at the present
      state of knowledge, these conditions might be best categorized as subgroups of
      the "Rett Complex," in which classical RS and the preserved speech variant may be
      the most frequent.

PMID- 9932239
TI  - Delayed language onset as a predictor of clinical symptoms in pervasive
      developmental disorders.
AB  - DSM-IV states that Asperger Disorder may be distinguished from Autistic Disorder
      by a lack of a delay in early language development. The aim of this study was to
      establish whether the presence or absence of early language delay would predict
      autistic symptomatology in children diagnosed with a PDD/autism spectrum
      disorder. Forty-six language-delayed and 62 normal language onset individuals (M
      age 11 years) were compared on ICD-10 research criteria and DSM-IV criteria,
      receptive language, and developmental history variables. Retrospective data were
      also obtained to determine whether language onset predicted autism symptomatology
      when young (< 6 years). We found that early language delay predicts more autistic
      symptomatology when young, but not at an older age. Early language delay is also
      associated with developmental motor milestone delays and lower receptive language
      abilities. The results question the use of early language delay as a valid
      discriminating variable between PDD subgroups.

PMID- 9932240
TI  - Procedures for teaching appropriate gestural communication skills to children
      with autism.
AB  - Four children with autism were taught to use gestures in combination with oral
      communication. Using a multiple-baseline across-responses design, intervention
      was introduced successively across three response categories containing gestures
      representative of attention-directing/getting, affective, and descriptive
      behavior. Although none of the participants displayed appropriate gestural and
      verbal responses during baseline, all participants acquired this skill with the
      systematic implementation of modeling, prompting, and reinforcement.
      Generalization measures indicated that the children learned to respond in the
      presence of novel stimuli and a novel setting. Social validity measures revealed
      that the participants' behavior appeared more socially appropriate at the
      completion of the study than at the start of the study, and that the
      participants' behavior was indistinguishable from that of their typically
      developing peers.

PMID- 9932241
TI  - Subtyping stereotypic behavior in children: the association between stereotypic
      behavior, mood, and heart rate.
AB  - The stereotypic behavior of children (N = 26) while in a playroom session with
      their parent was studied. The sample included children with a pervasive
      developmental disorder, an attention-deficit/hyperactivity disorder, a
      developmental expressive language disorder, or a developmental receptive language
      disorder and normally developing children. Stereotypic behaviors associated with
      distress, elation, and composure were compared on mean duration and form of the
      stereotypies and heart rate changes around the onset of the stereotypies. Results
      showed that stereotypies associated with different moods differed in all
      variables studied. Results confirm that a valid classification scheme for
      stereotypic behaviors is needed as they indicate different functions of
      individual stereotypies.

PMID- 9932242
TI  - Brief report: the development of the Children's Social Behavior Questionnaire:
      preliminary data.

PMID- 9932243
TI  - Brief report: the association of neurofibromatosis type 1 and autism.

PMID- 9932244
TI  - Brief report: treatment of echolalia in a girl with Rubinstein-Taybi syndrome:
      functional assessment of minimizing chances to provoke echolalia.

PMID- 9932245
TI  - Hemoglobin and the brain: a piece of the autism puzzle?

PMID- 9932246
TI  - Critique of "Efficacy of vitamin B6 and magnesium in the treatment of autism".

PMID- 9932247
TI  - High dose vitamin B6 and magnesium in treating autism: response to study by
      Findling et al.

PMID- 9932248
TI  - Sonographic spectrum of the corpus luteum in early pregnancy: gray-scale, color,
      and pulsed Doppler appearance.
AB  - PURPOSE: We describe the gray-scale and Doppler sonographic features of the
      corpus luteum during the first trimester of pregnancy. METHODS: Using
      transvaginal sonography, we prospectively evaluated the ovaries of 160 patients
      with spontaneous singleton intrauterine gestations between 5 and 8 weeks'
      menstrual age. Size, sonographic appearance, resistance index, and peak systolic
      velocity were recorded. RESULTS: The corpus luteum was identified in 157 (98%) of
      160 patients. The mean diameter was 1.9 +/- 0.6 cm. The most common appearance
      was a round hypoechoic structure, found in 54 patients (34%). Other appearances
      included a cyst with a thick wall and anechoic center (43 patients, 27%), a cyst
      containing internal debris (36 patients, 23%), and a thin-walled simple cyst (24
      patients, 15%). Corpus luteal blood flow was visualized with color Doppler
      imaging in 92% (145/157) of patients in whom the corpus luteum was found. Color
      Doppler imaging typically revealed a circumferential rim surrounding part or all
      of the corpus luteum. Low-resistance blood flow was seen with pulsed Doppler
      interrogation, with a mean resistance index of 0.49 +/- 0.08 and mean peak
      systolic velocity of 17 +/- 10 cm/second. CONCLUSIONS: The corpus luteum in early
      pregnancy is routinely identified with transvaginal sonography and has a wide
      range of sonographic appearances. Recognizing the various appearances of the
      corpus luteum is important to avoid confusing them with true ovarian
      abnormalities.

PMID- 9932249
TI  - Contribution of transvaginal sonography to the evaluation of benign cervical
      conditions.
AB  - PURPOSE: We evaluated the role of transvaginal sonography in imaging the normal
      cervix and its benign changes. METHODS: This prospective study included 512
      postmenopausal women who underwent transvaginal sonography before hysterectomy
      and within 15 days of a colposcopy examination that showed no malignant findings.
      The sonographic findings were compared to the pathology report. RESULTS: Naboth's
      cysts were the most common sonographic finding (102 cases), followed by
      cervicitis (43 cases). In 26 cases, endocervical polyps were found
      sonographically, and in 20 cases myomas were found. In 321 cases, the cervix
      showed no sonographic abnormality. Pathologic studies showed 104 Naboth's cysts,
      25 cases of nonspecific cervicitis, 26 endocervical polyps, 21 myomas, and 336
      normal cervices. CONCLUSIONS: The sensitivity and specificity of transvaginal
      sonography in diagnosing normal cervices and benign changes of the cervix are
      high. Transvaginal sonography provides easily obtainable, reliable information
      about the cervix.

PMID- 9932250
TI  - Role of carotid sonography as a first examination in the evaluation of patients
      with transient ischemic attacks and strokes: benefit in relation to age.
AB  - PURPOSE: We studied the influence of age on the utility of carotid sonography in
      patients with transient ischemic attacks and strokes. METHODS: The results of
      Doppler ultrasound examinations of the carotid arteries in 613 consecutive
      patients with transient ischemic attacks (n = 450) or strokes (n = 163) were
      analyzed for different age groups. For each patient, the grade of stenosis was
      scored for the ipsilateral internal carotid artery. The results of the ultrasound
      examinations were correlated with angiographic findings and findings at
      endarterectomy. The extent of atherosclerosis for each age group was expressed as
      the ratio between the number of grade II-IV stenoses (> or = 50%) in the carotid
      arteries and the number of patients in that group ("atherosclerosis ratio").
      RESULTS: Under the age of 40 years, high-grade atherosclerotic stenoses were not
      found. However, 3 relatively young patients had dissections of the internal
      carotid arteries. The atherosclerosis ratio exceeded 0.5 for age groups 65-69
      years through 80+ years. Among the patients with high-grade stenoses, ischemic
      heart disease prevented endarterectomy in 63% of patients in age group 80+ years,
      44% in age group 75-79 years, and 26% in age group 70-74 years. CONCLUSIONS:
      Carotid sonography did not detect any significant atherosclerotic changes in
      young patients but was useful for diagnosing other etiologies of ischemic
      cerebral disease, eg, carotid dissection. At the other end of the spectrum, the
      impact of carotid sonography on patient management appears to be limited in
      patients over the age of 70 years. Carotid sonography seems to be most useful for
      patients 40-69 years old.

PMID- 9932251
TI  - Sonographic measurement of splenic length: correlation with measurement at
      autopsy.
AB  - PURPOSE: The purpose of this study was to determine the correlations between the
      sonographic measurement of splenic length and the actual splenic length, volume,
      and weight. METHODS: Before autopsy, sonographic measurements of splenic length
      were obtained in 30 cadavers, and these values were compared with the actual
      length, volume, and weight of the spleen at autopsy. RESULTS: There were clear
      linear correlations between maximum sonographic length and actual length (r =
      0.831), volume (r = 0.817), and weight (r = 0.810). CONCLUSION: This study shows
      that a single, simple sonographic measurement gives a clinically useful
      indication of true splenic size.

PMID- 9932252
TI  - Doppler sonographic assessment of functional response of the right and left
      portal venous branches to a meal.
AB  - PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood
      flow in the right and left portal vein branches before and after a standard meal.
      We also assessed the functional response of the right and left lobes of the
      liver. METHODS: Portal blood flow was measured by Doppler sonography in the left
      and right portal vein branches and main portal trunk in 20 healthy volunteers in
      both fasting and postprandial states. The ratio between portal blood flow and
      liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before
      the meal, a statistically significant difference in portal blood flow volume was
      observed between the right and left portal branches (p < 0.01). The right PFI
      (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly
      different (p < 0.01). The increase in portal venous blood flow after a meal was
      found to be greater in the left portal branch (128%) than in the right portal
      branch (78%). The postprandial PFI also differed significantly (right, 1.54
      ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that
      the left lobe of the liver has a better postprandial compliance than the right
      lobe has.

PMID- 9932253
TI  - Sonographic findings in testicular sarcoidosis simulating malignant nodule.
AB  - Testicular involvement by sarcoidosis is rare. We report a case of a patient with
      known sarcoid who had a unilateral testicular nodule with apparent capsular
      invasion on sonography. The epididymis was normal on both sides. Despite these
      atypical features, pathology showed the nodule to be a sarcoid granuloma. In
      patients with sarcoidosis, the differential diagnosis of an intratesticular mass
      should include testicular involvement by sarcoid.

PMID- 9932254
TI  - Doppler sonographic diagnosis of severe portal vein pulsatility in constrictive
      pericarditis: flow normalization after pericardiectomy.
AB  - This case report describes the noninvasive assessment of hepatic and portal vein
      hemodynamics in a patient with constrictive pericarditis before and after
      pericardiectomy. Doppler sonography of the hepatic veins demonstrated a typical W
      shaped pattern with pronounced late diastolic flow reversal that disappeared
      after surgery. Preoperatively, we observed severe pulsatility of the portal vein
      with flow reversal in systole; after pericardiectomy, portal venous flow was
      normal. We concluded that the high right atrial pressure in this patient might
      have led to increased hepatic venous outflow resistance, with subsequent trans
      sinusoidal shunting between the hepatic artery and portal vein causing severe
      portal vein pulsatility. After pericardiectomy and a decrease in right atrial
      pressure, portal vein flow normalized.

PMID- 9932255
TI  - Inflammatory fibroid polyp presenting with intestinal invagination: sonographic
      and correlative imaging findings.
AB  - We report a case of a large inflammatory fibroid polyp of the small bowel
      presenting with intussusception in a 22-year-old man. Sonography demonstrated a
      solid, mobile, homogeneous, echogenic mass surrounded by the typical mural layers
      of an invaginated ileum. CT demonstrated a well-defined intraluminal solid mass
      with an attenuation of 17 HU. The pathologic diagnosis after segmental ileal
      resection was ileal inflammatory fibroid polyp.

PMID- 9932256
TI  - Multimodality demonstration of primary splenic angiosarcoma.
AB  - Angiosarcomas are rare, accounting for only 1-2% of all soft tissue sarcomas.
      Primary abdominal angiosarcomas usually arise in the liver or spleen. We report
      the first color Doppler findings of a rare, low-grade splenic angiosarcoma in a
      52-year-old woman.

PMID- 9932257
TI  - Preoperative sonographic diagnosis of acute appendicitis caused by Ascaris
      lumbricoides.
AB  - Acute appendicitis caused by Ascaris lumbricoides is an uncommon variant of a
      common disease. We describe a case in which sonography was used for preoperative
      diagnosis of ascaris appendicitis.

PMID- 9932258
TI  - Virtual endoscopy (VE) of the basal cisterns: its value in planning the
      neurosurgical approach.
AB  - Virtual endoscopy (VE) is a postprocessing technique based on a diverging ray
      casting algorithm to create perspective 3 D-images from computed tomographic
      angiography (CTA) and high resolution magnetic resonance imaging (MR) data. By
      applying VE to aneurysms, tumors, and vascular compression syndromes within the
      basal cisterns, endoscopic-like views of these structures are achieved from an
      intracisternal point above the cranial base. These views closely simulate the
      surgeon's impression during intraoperative endoscopy or microscopy and facilitate
      preoperative planning of different approaches.

PMID- 9932259
TI  - Frameless stereotactic-directed tissue sampling during surgery of suspected low
      grade gliomas to avoid histological undergrading.
AB  - Detection of anaplastic tumor foci for precise grading of gliomas is crucial for
      prognostic assessment and appropriate postoperative treatment planning. To
      avoided undergrading in large suspected low-grade gliomas, we employed frameless
      sterotaxy during open surgery for tissue sampling of radiologically suspected
      anaplastic foci. In nine patients (mean age 44 years, range 10-67) with large
      supratentorial suspected low-grade gliomas (32.4 ccm mean vol, range 17.9-68.6
      ccm) with small contrast enhancing areas (7.7% mean of total volume, range 0.7
      15.3%), a neuronavigation system with a pointer device (Easy Guide System
      Philips) or a navigating microscope (MKM System Zeiss) was used to target small
      enhancing tumor parts for cytological investigation during open surgery.
      Consecutive cytological smears revealed anaplastic tumor foci in all patients,
      correlating with neuroradiologically demonstrated small contrast enhancing areas,
      although biopsies from all other tumor parts showed low-grade tumors. Final
      neuropathological diagnosis confirmed anaplasia within the neuroradiologically
      suspected low-grade gliomas in all patients (2 grade IV, 5 WHO grade III and 2
      grade II-III tumors, WHO classification). In our experience frameless
      stereotactic-directed intraoperative tissue sampling during open surgery of large
      suspected low-grade gliomas helps to identify small anaplastic areas in mostly
      large low-grade tumors, and therefore, permits optimum planning of postoperative
      treatment.

PMID- 9932260
TI  - Stereotactic-guided microsurgical removal of lesions without cortical appearance
      planned by three-dimensional CT reconstruction: limits and advantages of the
      frame-based technique.
AB  - Intraoperative positioning still constitutes a basic problem in the microsurgical
      removal of intracerebral lesions, either deep-seated or without cortical
      appearance. We treated different types of lesions (cavernous angiomas,
      intraventricular tumors, gliomas, and metastases), by combining stereotactic
      targeting with the standard microsurgical technique. The dedicated software for
      the three-dimensional reconstruction of stereotactic CT images allowed us to
      determine the least traumatic surgical trajectory and the exact location of the
      lesion intraoperatively, with minimum manipulation of healthy cerebral tissue. We
      believe that the main indication for this technique is the removal of small,
      encapsulated or well-defined lesions without cortical appearance or in critical
      areas, while a direct inspection of the area is still essential in order to
      evaluate surgical removal in the case of infiltrating tumors.

PMID- 9932261
TI  - Variations in the site and size of third ventriculocisternostomy.
AB  - Seventy-eight cases of late-onset, non-communicating hydrocephalus were operated
      upon by third ventriculocisternostomy. The distortion in the anatomy of the
      dilated third ventricular floor dictated the selection of the target area. The
      optimal site for the perforation was the translucent, bluish and thinned out part
      of the floor. This was variable and in 76.9% not in the midline with more than
      one fenestra done in 35.9%. the size of the ventriculocisternostomy needed not be
      around 5 mm. Smaller sized openings in a taut floor (60.3%) served the same
      purpose as bigger ones in a redundant area (39.7%). The success of the procedure
      could be predicted from the profuse downward flow of cerebrospinal fluid through
      the perforation, "Whirl Sign". An acceptable assurance of our results was
      confirmed both clinically and radiologically. The outcome in our series had four
      grades, namely cured in 78.2%, ameliorated, but still needed diversion, in 16.7%,
      status quo in 2.5%, and complicated in 2.5%.

PMID- 9932262
TI  - How to perforate safely a resistant floor of the 3rd ventricle? Technical note.
AB  - Third ventriculostomy for acquired non-communicating hydrocephalus is an
      excellent alternative to shunting procedures. Nevertheless, complications can be
      severe and even fatal (e.g., lesion of the basilar artery), especially if the
      floor of the 3rd ventricle is very tough and/or opaque. The authors describe a
      safe method of sharp perforation of the floor, which should be applied if blunt
      fenestration cannot be achieved easily.

PMID- 9932264
TI  - Posterolateral approach for anteriorly located cervical spine tumors: technical
      note.
AB  - Cervical spinal cord tumors located anteriorly to the spinal cord often require
      an extensive anterior vertebrectomy approach for their removal followed by bone
      fusion and postoperative immobilization. To minimize the invasiveness of the
      conventional anterior approach for those tumors, the author has utilized the
      anterolateral approach which was originally developed for spondylotic disc
      disease. However, some of those tumors still can be removed by a less invasive
      posterior approach which violates spinal integrity to a much lesser degree.
      Anteriorly located tumors, in which the tumor-cord interface line extends
      posteriorly to a horizontal line drawn along the posterior margin of the
      vertebral body, can be removed by the posterolateral approach with a skin
      incision made at the point where the tumor-cord line intersects. Because the
      facet joint is thin and the pedicle is shallow in the cervical spine, only a
      hemilaminectomy bone window is required in this posterolateral approach for
      removal of such tumors. Surgical techniques of this posterolateral approach for
      removal of anteriorly located cervical cord tumors are described with two
      illustrated patients.

PMID- 9932263
TI  - Eyebrow keyhole approach in vascular neurosurgery.
AB  - The authors review their experience in the surgery of intracranial aneurysms via
      an eyebrow keyhole approach. The eyebrow keyhole approach presumes a skin
      incision in the lateral two-thirds of the eyebrow followed by small supraorbital
      craniotomy (15 x 25 mm). Using this approach and an intraoperative endoscope for
      better visualisation of the aneurysmal neck, the authors operated on thirty-seven
      patients with forty intracranial aneurysms. There was no mortality, postoperative
      recovery was fast, and the cosmetic effect was excellent. Advantages and
      possibilities of this approach are discussed and results are presented. The
      authors recommend this approach as a minimal invasive surgery procedure in the
      treatment of intracranial aneurysms. When performed by experienced vascular
      neurosurgeons this approach is neither more difficult for the surgeon nor more
      dangerous for the patient than any other standard craniotomy procedure. According
      to the authors' present results, surgery of intracranial aneurysm via an eyebrow
      keyhole approach is the method of choice when performed by an experienced
      vascular neurosurgeon.

PMID- 9932265
TI  - Radical surgery and reoperation in supratentorial malignant glial tumors.
AB  - The treatment modalities for gliomas are still questioning and searching. We
      reviewed the effect of the extent of surgical resection and reoperation on the
      length and quality of survival in 152 consecutive patients who underwent
      operation for supratentorial gliomas at GATA Neurosurgery clinic between 1985 to
      1995. Seventy-two patients (50%) had glioblastoma multiforme (GBM), and 48
      patients (33%) had anaplastic astrocytoma (AA). Gross total resection was
      achieved in 70 cases (49%), subtotal resection was performed in 60 cases (42%),
      and biopsy was carried out in 14 cases (9%). Thirty-two patients were reoperated
      for recurrency and the median interval between the first operation and
      reoperation was 9.5 months in glioblastoma multiforme, and 11.7 months in
      anaplastic astrocytoma. The resection groups were compared for age, sex,
      preoperative and postoperative Karnofsky rating, tumor location, postoperative
      radiation therapy, and chemotherapy, and survival according to multivariate
      analysis. Preoperative Karnofsky rating and surgical resection type were the most
      important factors related to survival after operation or reoperation. The gross
      total resection group lived longer than the subtotal resection group by life
      table analysis. Median survival of GBM was 76 weeks in gross total resection
      group, and 33 months in AA group with total resection (p < 0.001). Preoperative
      Karnofsky scores had a statistically significant effect on the quality of life
      and survival after operation and reoperation in all cases (p = 0.005). Radical
      surgery and reoperation also improve quality and length of life in selective
      malignant supratentorial gliomas.

PMID- 9932266
TI  - Percutaneous transluminal angioplasty using kissing balloon technique for carotid
      bifurcation stenoses coupled with the proatlantal intersegmental artery: a case
      report.
AB  - A 65-year-old man, who suffered from recurrent syncopal attacks after a minor
      stroke, was treated by percutaneous transluminal angioplasty using the kissing
      balloon technique (KBT) in which two angioplasty balloons were inflated
      simultaneously for the right carotid bifurcation stenoses. Because they involved
      the right internal carotid artery and the right external carotid artery coupled
      with the right proatlantal intersegmental artery, neither of them should close
      after the angioplasty. Bifurcation stenoses were sufficiently dilated with KBT
      and no syncopal attacks have recurred since the treatment.

PMID- 9932267
TI  - Optimized evaluation of a pulsed 2.09 microns holmium:YAG laser impact on the rat
      brain and 3 D-histomorphometry of the collateral damage.
AB  - Since more than 20 years CO2 and Nd:YAG lasers are established in the
      microsurgery of the nervous system. CO2 lasers can be used handheld, but may be
      focused on the target area by mirror optics and sideports of the operating
      microscope's micromanipulator. Nd:YAG lasers have the disadvantage of deep
      penetration into the brain and provocation of a large collateral damage. The need
      is for a fibre conducted solid system for surgery in delicate areas as for brain
      stem surgery. Fibre conduction of near infrared lasers allows better exposure of
      the target area compared to hollow wave guides or mirror equipment. Fibres can be
      tapered and modified according to the purpose. The holmium:YAG (Ho:YAG) laser has
      acquired interest by introducing the system into microsurgery of parenchymal
      tissue. They have not been proven yet sufficiently for neurosurgical tasks. The
      effort to minimalize the collateral tissue damage has to be maximalized in the
      surgery of nervous tissue and functional low redundant brain stem or spinal cord
      tissue. Volumetric data may be more precise in comparison to depth and width data
      of the laser lesion even when the different levels of the tissue interaction have
      to be analyzed for estimation of the real side effects in nervous tissue. We have
      used 50-800 ml delivered Ho:YAG single pulses in cortical areas of Sprague-Dawley
      rats and investigated the different lesion zones by volumetric data. The
      functional lesion zone was detected and measured by immunohistological staining
      of the heat shock protein HSP 72. For further reduction of the focus area, we
      have used tapered 400 to 200 microns fibres.

PMID- 9932268
TI  - Pediatric oncology and hematology in Birmingham, England.
AB  - The hematology and oncology service at Birmingham Children's Hospital was
      established in the late 1960s and now is one of the largest in the United
      Kingdom. It provides comprehensive care for the entire range of childhood
      malignancies, coagulation disorders, and hemoglobinopathies and other
      hematological disorders, and undertakes bone marrow transplant and
      megatherapy/peripheral blood stem cell procedures. Research includes clinical
      trials of treatments of childhood cancers; molecular biology studies on leukemia,
      Hodgkin's disease, neuroblastoma, and sarconas; childhood cancer epidemiology,
      and geographical and racial incidence; and treatment of hemophilia and molecular
      investigation of coagulation disorders. These activities involve collaboration
      with local, national, and international research groups.

PMID- 9932269
TI  - Neuropsychological functioning after treatment for hematological malignancies in
      childhood, including autologous bone marrow transplantation.
AB  - Neuropsychological functioning and academic achievement were assessed in 26
      patients 2-10 years after autologous bone marrow transplantation (ABMT) for
      childhood hematological malignancies. Serial tests of general intelligence before
      and after ABMT were supplemented with a cross-sectional study of
      neuropsychological functioning. Test results for general intelligence were in the
      normal range and mainly unaffected over time, but below average performance in
      specific neuropsychological tests was found in a higher number of children than
      expected, especially for the variables "Strategies," "Attention," and "Memory."
      All school children were in regular classes; 5/15 obtained extra tutorial help
      and two of them had major learning difficulties. Eight young adults reported
      normal academic achievement. Low age at diagnosis and long time since ABMT
      correlated significantly with lower test results on general intelligence and
      "Attention," and high intensity of treatment directed to the central nervous
      system correlated with more learning difficulties as assessed by teachers.
      Children with identified problems in school were offered educational counseling
      based on their test profiles. To enable such counseling, it is suggested that
      both IQ tests and neuropsychological tests on memory and attention be included in
      follow-up programs for children who have received high-intensity cancer
      treatment.

PMID- 9932270
TI  - Growth hormone deficiency following radiotherapy for orbital and parameningeal
      sarcomas.
AB  - Growth hormone deficiency (GHD) is a recognized late effect of successful
      treatment of tumors requiring cranial irradiation. Growth after treatment was
      assessed in 16 patients with sarcomas of the orbital and parameningeal regions.
      Median age at diagnosis was 6.35 years and median follow-up was 7.2 years.
      Treatment consisted of combination chemotherapy and radical radiotherapy,
      conventionally fractionated with a median dose 4500 cGy; the
      hypothalamic/pituitary region received a median dose of 4163 cGy. Height was
      measured every 6 months and 13/16 patients underwent tests of GH function. At GH
      testing median height standard deviation score (SDS) was -0.7, a median decrease
      of -0.55 since tumor diagnosis. Seven patients were treated with human GH (hGH)
      at a median of 3.7 years from tumor diagnosis and followed for a median of 2.7
      years. Treatment with hGH resulted in a median increase in height SDS of 0.9.
      Careful surveillance with timely introduction of GH replacement is required for
      treatment of GHD following treatment of orbital and parameningeal sarcomas.

PMID- 9932271
TI  - Arm anthropometry in evaluation of malnutrition in children with cancer.
AB  - Malnutrition in children with cancer is reported to be relatively uncommon at the
      time of diagnosis. However, in most studies nutritional status measurement has
      relied almost exclusively on weight-related indices. This can be misleading,
      because in children with malignancy, tumor masses can reach more than 10% of
      total body weight. A controlled study was performed in 62 patients using arm
      anthropometry to provide a more accurate evaluation of the nutritional status of
      children with cancer at presentation. Height, weight, midupper arm circumference
      (MUAC), and triceps skinfold thickness (TSFT) were measured in all patients (40
      boys, 22 girls) and controls (18 boys, 13 girls). Weight for height (WFH) of each
      patient was compared with the national standards. MUAC and TSFT were also
      interpreted according to the standards developed by A. Roberto Frisancho. The
      mean ages were 6.5 +/- 3.7 years (range 0.08-13) and 5.7 +/- 4.7 years (range
      0.25-15) in patients and control group, respectively. Results showed that
      although the WFH values for patients were normal, MUAC and TSFT values were
      significantly less than control values (P < 0.001). Moreover, 27% of patients
      showed malnutrition (they had MUAC and TSFT below 5th percentile). Patients with
      intraabdominal solid tumors had significantly lower MUAC and TSFT values than
      those with extraabdominal solid tumors (P < 0.05). The data strongly indicate
      that malnutrition is common at the time of diagnosis in children with cancer, and
      arm anthropometry should replace the use of weight-related indices to identify
      malnutrition in children.

PMID- 9932272
TI  - Psychiatric disorders among parents of children suffering from acute
      lymphoblastic leukemia.
AB  - The aim of the study was to assess the frequency and likely associations of
      psychiatric disorders in parents of children suffering from acute lymphoblastic
      leukemia (ALL). One parent each of 30 consecutive ALL patients who achieved their
      first remission were interviewed and rated on the Comprehensive
      Psychopathological Rating Scale. Ratings were also made on the Hamilton
      Depression Rating Scale and the State Trait Anxiety Inventory. Fifty percent (n =
      15) of the parents had psychiatric disorders, namely neurotic depression (n = 11,
      36.7%) and adjustment disorder with depressed mood (n = 4, 13.3%). These
      disorders were of mild to moderate severity and were perceived to be highly
      treatable. Psychiatric morbidity was associated with women and unemployment. A
      score of 14 on the Hamilton Depression Rating Scale provided a reliable cutoff
      for selection of subjects for referral.

PMID- 9932273
TI  - Psychiatric morbidity in children suffering from acute lymphoblastic leukemia.
AB  - The study aimed at assessing the frequency of psychiatric disorders in children
      with acute lymphoblastic leukemia. Thirty consecutive subjects in the age range
      of 6-12 years were interviewed with the help of a symptom checklist soon after
      they had achieved their first remission. The children were also administered the
      Children's Depression Rating Scale and the State Trait Anxiety Inventory for
      Children. One-third (n = 10) of the subjects received a diagnosis according to
      the International Classification of Diseases, 9th ed. Ninety percent (n = 9) had
      emotional disorders. All the disorders were mild to moderate in intensity and
      were perceived to be easily treatable.

PMID- 9932274
TI  - The serum transferrin receptor concentration in seven fetuses with hemolytic
      disease.
AB  - Six pregnant women who received intrauterine transfusions and their seven fetuses
      were followed during gestation. Hemoglobin concentration, hematocrit value, serum
      ferritin, and serum transferrin receptor (TfR) concentrations were measured. In
      the fetal samples, there was a tendency for the TfR concentration to decrease
      during gestation and after the intrauterine transfusions. Serum TfR values varied
      between 0.7 and 5.2 mg/L, which is near the postnatal level measured in premature
      infants. On the contrary, one would have expected to find highly elevated values
      due to the active fetal erythropoiesis. The fetal regulation of TfR production
      may differ from that described postnatally.

PMID- 9932275
TI  - The stomach and pulmonary interlobular space as unusual sites of osteosarcoma.
AB  - The authors report a girl with high-grade intraosseous osteosarcoma of the left
      femur who lost one eye during early infancy for an unknown reason. Nine months
      after treatment, osteosarcoma in the stomach was detected and completely excised
      when the girl underwent endoscopy for Helicobacter pylori infection. Three years
      later osteosarcoma in the pulmonary interlobular space was noticed and completely
      removed. The girl is doing well and free of disease 26 months after the last
      resection.

PMID- 9932276
TI  - Malignant hypertension and paraganglioma in a 14-year-old girl.
AB  - A 14-year-old girl presented with malignant hypertension. Physical examination
      and abdominal computerized tomography revealed a paraaortic mass. Urinary
      catecholamines, serum renin, and aldesterone levels were high. The mass was
      totally excised and a paraganglioma of the organ of Zuckerkandl was confirmed.
      The hypertension resolved after surgery.

PMID- 9932277
TI  - Facial nerve palsy in an infant with hemophilia A.
AB  - A 5-month-old infant with hitherto undiagnosed hemophilia A, who developed a
      unilateral lower motor neurone type of facial palsy, is described. A high
      resolution CT scan confirmed the nerve palsy to be a consequence of a
      hemotympanum. The patient recovered completely in 7-10 days after therapy with
      factor VIII concentrate.

PMID- 9932278
TI  - Acute lymphoblastic leukemia complicated by choroid plexus carcinoma.
AB  - A 14-year-old boy with acute lymphoblastic leukemia in remission developed
      headaches characteristic of migraines. His neurologic examination was normal,
      serial studies of cerebrospinal fluid were unremarkable, and the headaches
      responded promptly to antimigraine therapy. Ultimately, radiographic and
      pathologic examinations demonstrated a choroid plexus carcinoma.

PMID- 9932279
TI  - Infantile megaloblastosis secondary to acquired vitamin B12 deficiency.

PMID- 9932280
TI  - Transient hypoplastic anemia of childhood.

PMID- 9932281
TI  - Apoptosis in developing retinal tissue.
AB  - The mechanisms of apoptosis are strongly dependent on cell-cell interactions
      typical of organized tissues. Experimental studies of apoptosis using a
      histotypical preparation of retinal explants are reported in the present article.
      We found that various characteristics of apoptosis are selectively associated
      with retinal cell death depending on cell type, stage of maturation, and means of
      induction of apoptosis. Among these were: (1) the requirements of protein
      synthesis; (2) the role of cAMP; (3) the expression of certain apoptosis
      associated proteins; and (4) the sensitivity to excitotoxicity, modulation of
      protein phosphatases and calcium mobilization. Dividing cells undergo apoptosis
      in response to several inducers in specific phases of the cell cycle, and in
      distinct regions within their pathway of interkinetic nuclear migration. Recent
      post-mitotic cells are selectively sensitive to apoptosis induced by blockade of
      protein synthesis, while both proliferating and differentiated cells are more
      resistant. We also studied the association of several proteins, some of which
      play critical roles in the cell cycle, with both differentiation and apoptosis in
      the retinal tissue. Detection of cell cycle markers did not support the
      hypothesis that retinal cells re-enter the cell cycle on their pathway to
      apoptosis, although some proteins associated with cell proliferation re-appeared
      in degenerating cells. The transcription factors c-Jun, c-Fos and c-Myc were
      found associated with apoptosis in retinal cells, but their sub-cellular location
      in apoptotic bodies is not consistent with their canonical functions in the
      control of gene expression. The bifunctional redox factor/AP endonuclease Ref-1
      and the transcription factor Max are associated with progressive cell
      differentiation, and both are down-regulated during cell death in the retina. The
      data suggest that Ref-1 and Max may normally function as negative modulators of
      retinal apoptosis. The results indicate that nuclear exclusion of transcription
      factors and other important control proteins is a hallmark of retinal apoptosis.
      Histotypical explants may be a choice preparation for the experimental analysis
      of the mechanisms of apoptosis, in the context both of cell-cell interactions and
      of the dynamic behavior of developing cells within the organized retinal tissue.

PMID- 9932282
TI  - Matrix and the retinal pigment epithelium in proliferative retinal disease.
AB  - In their normal state, RPE cell are strongly adherent to Bruch's membrane.
      Certain pathological conditions such as retinal detachment cause an injury-type
      response (probably augmented or induced by the local accumulation of a variety of
      substances which modulate cell behaviour) in which RPE begin to dissociate from
      the membrane. This RPE-Bruch's membrane separation may be mediated by proteins
      with counter-adhesive properties and proteolytic enzymes, partly derived from the
      RPE themselves. Concomitant with the RPE disassociation, the cells begin to lose
      tertiary differentiation characteristics and gain macrophage-like features. When
      the "free" RPE arrive at the surface of the neuroretina, they may attach to or
      create a provisional matrix. Some of the cells adopt a fibroblast-like phenotype.
      This phenotype is similar to that of the dermal fibroblast during cutaneous wound
      repair and the fibroblastic RPE synthesise the types of matrix components found
      in healing skin wounds. Many of these molecules in turn further modulate the
      activities of the cells via several families of cell surface receptors, while the
      RPE continue to remodel the new matrix with a range of proteolytic enzymes. The
      resulting tissue (or membrane) has many of the features of a contractile scar and
      is the hallmark of the condition known as proliferative vitreoretinopathy (PVR).
      Thus the development of PVR, and the resulting tractional distortion of the
      neuroretina, appears to be dependent on RPE-matrix interactions. The interactions
      present a number of potential therapeutic targets for the management of the
      disorder.

PMID- 9932283
TI  - Retinal and optic nerve head ischemic disorders and atherosclerosis: role of
      serotonin.
AB  - Ischemic disorders of the retina and optic nerve head (OPH) constitute a common
      cause of visual loss in the middle-aged and elderly population. These disorders
      have a high association with atherosclerosis. This review has considered the
      various aspects of atherosclerosis and its role, as well as that of serotonin, in
      the development of ischemic disorders of the retina and ONH. It is known that
      when platelets aggregate on an atheromatous plaque, serotonin is one of the
      agents released. Studies in experimental atherosclerotic monkeys have shown that,
      although serotonin has no effect on ocular vasculature in normal monkeys, in
      atherosclerotic monkeys it produces vasopasm of the central retinal artery (CRA)
      and/or posterior ciliary artery (PCA) in various combinations but not vasopasm of
      the arterioles in the retina; vasospasm of the CRA and/or PCA(s) can consequently
      cause transient, complete occlusion or impaired blood flow in these arteries. It
      is postulated that in some atherosclerotic individuals this mechanism may play an
      important role in the development of ischemic disorders of the retina and ONH,
      including amaurosis fugax, (CRA) occlusion and anterior ischemic optic
      neuropathy, and possibly also glaucomatous optic neuropathy, particularly in
      normal tension glaucoma. Studies have also shown that dietary treatment of
      atherosclerosis abolishes or markedly improves the serotonin induced
      vasoconstriction within a few months. All these considerations may have important
      implications for our understanding of the pathogenesis and management of these
      blinding disorders.

PMID- 9932284
TI  - The relationship between cataract, cell swelling and volume regulation.
AB  - The cause of cataracts is not known. Data from epidemiological and case-control
      studies have suggested various risk factors, among them; sunlight, diabetes,
      diarrhoea, oxidative stress, smoking and alcohol. Many reports in the literature
      suggest that the hydrated state of the lens is linked to cataract and recently
      direct evidence has emerged linking lens swelling to cataract. This review
      attempts to collate the various strands of evidence relating the hydrated state
      of the lens in cataract and to construct a common pathway for cataractogenesis.
      This common pathway involves lens swelling, membrane permeabilization, vacuole
      and cleft formation, disturbance to the intracellular environment, protein
      aggregation/modification and light scatter. This hypothesis gives rise to some
      testable predictions amongst which is that under certain conditions the lens
      axial diameter will increase raising the possibility that pre-cataractous changes
      could be detected (e.g., by ultrasound) and, with appropriate action, the
      cataract could be prevented or delayed. There are encouraging signs from animal
      studies that certain types of lens opacification can be delayed or prevented,
      lending credibility to the objective of cataract prevention in humans. Even a
      delay in the onset of cataract would have a huge global impact. The incidence of
      cataract correlates with poverty, poor diet and poor hygiene and the vast
      majority of cataract is found in developing countries. Economic factors and a
      lack of cataract surgeons in these countries mean that surgery is not the long
      term answer. Prevention is the only realistic global approach. This review
      concludes that detection of pre-cataractous changes and cataract prevention are
      achievable objectives and funds should be directed towards their realization.

PMID- 9932285
TI  - Cataract mutations and lens development.
AB  - The lens plays an essential role for proper eye development. Mouse mutants
      affecting lens development are excellent models for corresponding human
      disorders. Moreover, using mutations in particular genes the process of eye and
      lens development can be dissected into distinct steps. Therefore, three mouse
      mutants will be described in detail and discussed affecting three essential
      stages: formation of the lens vesicle, initiation of secondary lens fiber cell
      formation, and terminal differentiation of the secondary fiber cells. The mutant
      aphakia (ak) has been characterized by bilaterally apakic eyes [Varnum and
      Stevens (1968) J. Hered. 59, 147-150], and the corresponding gene was mapped to
      chromosome 19 [Varnum and Stevens (1975) Mouse News Letters 53, 35]. Recent
      investigations in our laboratory refined the linkage 0.6 +/- 0.3 N cm proximal to
      the microsatellite marker D19Mit10. The linked gene Pax2, responsible for proper
      development of the posterior part of the eye and the optic nerve, was excluded as
      candidate gene by sequence analysis. Histological analysis of the homozygous ak
      mutants revealed a persisting lens stalk and subsequently the formation of lens
      rudiments. The lens defects led to irregular iris development and retinal
      folding. Congenital aphakia is known as a rare human anomaly. Besides a corneal
      dystrophy (CDTB), no corresponding disease is localized at the homologous region
      of human chromosome 10q23. The Cat3 mutations are characterized by vacuolated
      lenses caused by alterations in the beginning of secondary lens fiber cell
      differentiation at embryonic day 12.5. Secondary malformations develop at the
      cornea and the iris, but the retina remains unaffected. Two mutant alleles of the
      Cat3 locus have been mapped to mouse chromosome 10 very close to the
      microsatellite markers D10Mit41 and D10Mit95 (less than 0.3 cM). Since Cat3 is
      mapped to a position, which is homologous to human chromosome 12q21-24, the
      disorder cornea plana congenita can be considered as a candidate disease. The
      series of Cat2 mutations have been mapped close to the locus encoding the gamma
      crystallin gene cluster Cryg [Loster et al. (1994) Genomics 23, 240-242]. The
      Cat2nop mutation is characterized by a deletion of 11 bp and an insertion of 4 bp
      in the 3rd exon of Crygh leading to a truncated gamma B-crystallin. The defect in
      the Crygh gene is causative for the stop of lens fiber cell differentiation from
      embryonic day 15.5 onward. Besides the lens, no further ocular tissue is
      affected. The Cat2 mouse mutants are interesting models for human cataracts
      caused by mutations in the gamma-crystallin genes at human chromosome 2q32-35.
      The ak, Cat3 and Cat2 mutants are discussed in the context of other mutants
      affecting early eye and lens development. Additionally, human congenital
      cataracts are discussed, which have been characterized similar to the mouse
      models. The overview of the three types of mutants demonstrates that genes, which
      affect the early eye development, e.g. at the lens vesicle stage, have
      consequences for the development of the whole eye. In contrast, if the mutation
      influences later steps of lens differentiation, the consequences are restricted
      to the lens only. These data indicate a decreasing effect of the lens for the
      regulation of eye development during embryogenesis.

PMID- 9932286
TI  - N-type voltage-sensitive calcium channel interacts with syntaxin, synaptotagmin
      and SNAP-25 in a multiprotein complex.
AB  - Expression of the N-type voltage sensitive calcium channel in Xenopus oocytes
      along with syntaxin and p65 showed that the syntaxin-modified N-type channel
      properties, were fully reversed by p65. The inward current was restored to a
      significantly higher amplitude when all three proteins were present, suggesting
      that the channel interacts with syntaxin, p65 and SNAP-25 in a quaternary
      complex. Further support to a multicomplex formation between the channel and the
      synaptic proteins was drawn from the steady-state voltage inactivation profiles.
      A physical interaction of the N-type calcium channel with the vesicular protein
      synaptotagmin (p65) was demonstrated biochemically, using recombinant fusion
      proteins. The interaction is confined to a cytosolic channel domain that
      separates segments II and III amino acids 710-1090 of the N-type channel (N
      Loop710-1090). In vitro binding of recombinant N-Loop710-1090 to p65 (amino acids
      96-421) involves the two C2 domains of p65, C2A domain [amino acids 96-265; p65(1
      3)] and C2B domain [amino acids 248-421; p65(3-5)]. While the binding of C2A and
      C2B domains was calcium independent, C2B domain binding to the N-Loop was
      inositol-hexaphosphate (IP6)-sensitive. The N-Loop710-1090 binding to p65 was
      competed by syntaxin and SNAP-25, which are synaptic plasma membrane proteins.
      These combined functional and biochemical approaches provide evidence for a
      complex formation between the N-type channel and the exocytotic machinery which
      by generating fusion-competent vesicles may function to regulate the process of
      synaptic secretion.

PMID- 9932287
TI  - Immunohistochemical localization of angiotensin II receptors (AT1) in the heart
      with anti-peptide antibodies showing a positive chronotropic effect.
AB  - Antibodies were produced against a synthetic peptide corresponding to amino acids
      (165-191) of the second extracellular loop of the human angiotensin II receptor
      subtype 1 (AT1) in rabbits. The purified antibodies had an apparent affinity of
      about 1 nM and were monospecific for the AT1-receptor peptide. Chemical
      modification of the carboxyl groups (glu at positions 173 and 185) and the
      sulfhydryl group (cys at position 180) of the AT1-receptor peptide did not alter
      the relative affinity of the coated AT1-receptor peptide to antibodies. The
      antibodies specifically stained CHO cells expressing the rat AT1a receptor.
      Immunoblots on rat kidney revealed that the antibody recognized a protein band of
      59 +/- 3 kDa in a dose-dependent manner and this band was no longer detected
      after preincubating the antibodies with AT1-receptor peptide. Using electron
      microscopic and immunofluorescence immunocytochemistry techniques, angiotensin II
      receptors were detected in (1) the sarcolemma, T-tubules and nuclei of rat
      cardiomyocytes, (2) the transluminal side of endothelial cells and (3) fibroblast
      cells. These localizations are specific, as the immunostaining did not appear
      when preimmune rabbit serum was used and was blocked after preincubating
      antibodies with antigenic peptide. Functionally, these antibodies did not affect
      the ligand binding properties of the receptors but displayed agonist-like
      activity as shown by dose-dependent increases in beating frequency in cultured
      neonatal cardiomyocytes. These results suggest that the antibodies against the
      second extracellular loop of human AT1 receptors were able to specifically
      recognize AT1 receptors. In addition, they extend the observation that the second
      extracellular loop of the G-protein coupled membrane receptors is a specific
      target for antibodies with agonist-like activity.

PMID- 9932288
TI  - Cloning, gene structure and genomic localization of an orphan transporter from
      mouse kidney with six alternatively-spliced isoforms.
AB  - Two genes were identified and characterized that express cDNAs related to
      previously identified neurotransmitter and/or osmolyte transporters, but which
      are expressed specifically in the kidney. RNA transcribed from one of these two
      genes (XT2) was found to undergo an extensive degree of alternative splicing to
      generate six distinct isoforms. The intron-exon structure of the XT2 gene and the
      sites of alternative splicing were identified. Expression of the second gene
      (XT3) was found to be conserved in human kidney, and partial sequence was
      obtained from a human cDNA library. The expressions of both XT2 and XT3 RNAs were
      determined in mouse and human tissues, respectively, and the locations of the two
      genes within the mouse genome were identified. Screening experiments to identify
      the substrate(s) of these proteins failed to identify specific uptake with any of
      the tested compounds; however, immunofluorescent microscopy demonstrated that
      epitope-tagged variants of the protein products of the XT2 and XT3 cDNAs were
      present on the plasma membrane of transfected cells.

PMID- 9932289
TI  - Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous
      opening and unitary conductance of the ATP-sensitive K+ channels.
AB  - The ATP-sensitive K+ (KATP) channels, e.g. in heart and pancreatic beta-cells,
      open spontaneously in the absence of intracellular ATP (ATPi). Their unitary
      conductance is approximately 80 pS with 150 mM extracellular K+. These features
      are shared by the K+ channels composed of various sulfonylurea receptors (SURs)
      and Kir6.2, whereas SUR/Kir6.1 channels have a smaller conductance (approximately
      35 pS) and do not open spontaneously in the absence of ATPi. To identify the
      structural elements in Kir6.0 subunits which determine these properties, we
      analyzed the properties of functional K+ channels composed of SUR2A, the cardiac
      type SUR, and various chimeras of Kir6.1 and Kir6.2 heterologously expressed in
      HEK (human embryonic kidney) 293T cells. The analyses indicate that the
      extracellular linker domain between the two putative membrane-spanning regions is
      responsible for the difference in the single channel conductance between
      SUR2A/Kir6.1 and SUR2A/Kir6.2 channels. The cytosolic N-terminal domain of Kir6.2
      was mandatory for spontaneous channel opening in the absence of ATPi, although a
      part of C-terminus was also involved. These results implicate specific regions of
      Kir6.0 in the spontaneous opening and the single channel conductance.

PMID- 9932290
TI  - Identification of a novel G-protein coupled receptor expressed in distinct brain
      regions and a defined olfactory zone.
AB  - PCR-approaches with degenerated oligonucleotide primers have been employed in
      trying to identify novel members of the G-protein coupled receptor (GPCR)
      superfamily from rat brain. Screening a rat brain library with an amplification
      product showing some features of a GPCR gene led to the isolation of a full
      length clone (RA1c); the encoded polypeptide comprises seven distinct hydrophobic
      stretches as well as several other hallmarks of GPCRs. Sequence comparison
      revealed a rather low but significant homology to GPCRs; RA1c shares about 30%
      sequence identity with various olfactory receptors and about 27% with several
      peptide receptors. By Northern blot and especially by in situ hybridization
      analysis it could be demonstrated that the RA1c receptor is expressed only in
      very distinct areas of the brain and in addition in a defined zone of the
      olfactory epithelium.

PMID- 9932291
TI  - Nutrition and bone health: with particular reference to calcium and vitamin D.
      Report of the Subgroup on Bone Health, Working Group on the Nutritional Status of
      the Population of the Committee on Medical Aspects of the Food Nutrition Policy.

PMID- 9932292
TI  - In vivo versus in vitro produced bovine ova: similarities and differences
      relevant for practical application.
AB  - This present review describes some differences and similarities between bovine
      embryos produced in vivo and in vitro. The first part outlines the respective
      environments during maturation, fertilisation and early embryonic development of
      the two types of embryos and compares their morphological, biochemical and
      genomic characteristics. Results from comparative studies on embryo metabolism
      and gene expression reveal that most parameters are similar, but some significant
      differences of presumptive importance for normal development have been described.
      Morphologic and kinetic differences between in vitro and in vivo produced embryos
      are also well documented. However, improved culture conditions have been reported
      to minimise the differences. The second part focuses on the practical
      consequences of the differences in relation to embryo selection,
      cryopreservation, sanitary risks and pregnancy following transfer as well as
      normality of calves. Lower viability following transfer and increased
      susceptibility to cryopreservation of in vitro produced embryos is discussed.
      Finally and most importantly, reported evidence of increased sanitary risks and
      abnormal foetal development associated with in vitro produced embryos is
      presented.

PMID- 9932293
TI  - Cloning in cattle: from embryo splitting to somatic nuclear transfer.
AB  - The ability to obtain genetically identical offspring in cattle (clones) is
      useful for research and for potential applications to breeding schemes.
      Experimental possibilities for generating such animals have evolved considerably
      in the last two decades. Embryo splitting has become a relatively simple
      technique but is limited to twinning. Embryonic nuclear transfer has improved and
      is associated with sexing to generate sets of clones despite a great variability
      of results between parent embryos. The factors of progress are reviewed here.
      Recently, somatic cells used as a source of nuclei in bovine nuclear transfer has
      been demonstrated. Here we present the results of the developmental potential of
      nuclei from skin and muscle cells.

PMID- 9932294
TI  - Recent developments in embryo sexing and its field application.
AB  - This review focuses on polymerase chain reaction (PCR) sexing of bovine embryos
      in commercial situations with emphasis on new developments. Simplifications of
      the biopsy technique is one of the major simplifications over the last few years.
      The stabilization of the embryo by means of protein-free medium or scratches
      produced on the bottom of the Petri dish makes it possible to perform a biopsy
      with a single microinstrument. The traditional PCR sexing approach utilizes
      electrophoresis, which involves the risk of deoxyribonucleic acid (DNA)
      contamination of subsequent assays. Such contamination, resulting in females
      misdiagnosed as males, is avoided efficiently by using a non-electrophoretic
      method in which the sex is determined based on fluorescence of unopened tubes.
      However, female samples cannot be distinguished from blank samples in the non
      electrophoretic assay, which thus relies on accurate transfer of biopsy into
      tubes. Nevertheless, an accuracy of about 95% can be reached with both
      approaches. High pregnancy rates (50-70%) can be reached with biopsied Grade 1
      embryos, but there is evidence that pregnancy rates with Grade 2 embryos is 15
      20% lower. Recent data indicate that pregnancy rates of 50% can be achieved with
      frozen-thawed biopsied Grade 1 embryos. In conclusion, recent developments in
      biopsy techniques, detection systems and freezing should increase interest in PCR
      sexing.

PMID- 9932295
TI  - Embryo transfer and related technologies in sheep reproduction.
AB  - This paper reviews the status of embryo transfer and the major technologies
      applied to preimplantation of embryos in sheep. Embryo production from
      superovulated ewes is hindered by an unpredictable response to hormonal
      treatment. Progress in this area should be expected by an appropriated control of
      follicular development with gonadotropin-releasing hormone (GnRH) agonist or
      antagonist prior to gonadotrophin administration. Simple protocols for the
      cryopreservation of sheep embryos by vitrification are already available and the
      development of frozen-thawed blastocysts to term is close to the fresh ones.
      Further research is required to identify factors able to promote the maturation
      in vitro of oocytes, namely those obtained from prepubertal animals. Semen and
      embryo sexing procedures are available in cattle although much less attention was
      paid to their application to sheep. Among all the reproductive technologies,
      cloning with embryonic and foetal cells has progressed dramatically in sheep and
      nuclear transfer has been used to produce transgenic animals as an alternative to
      pronuclear injection. The production of the first lamb cloned from a somatic cell
      opened new opportunities in animal breeding as well as exciting lines of basic
      research. The overall conclusions are that, apart from superovulation, the
      application of in vitro technologies is likely to evolve rapidly and once
      applied, a great impact on traditional and new animal productions should be
      expected. However, a better understanding of the changes in gene expression,
      induced in embryos by different in vitro manipulation procedures, is necessary to
      prevent abnormal foetal development.

PMID- 9932296
TI  - Ultrastructural aspects of mammalian fertilization: new discoveries and
      inspirations from the work of Daniel Szollosi.
AB  - Our current level of knowledge on mammalian fertilization would not be attained
      without the contribution of ultrastructural studies. The late Daniel Szollosi, to
      whose memory this review is dedicated, was one of the most enthusiastic explorers
      of this fascinating field. In his landmark electron microscopic studies, he
      revealed the importance of nuclear envelope breakdown for oocyte maturation and
      its reconstitution after fertilization, and predicted the era of cloning by
      publishing articles on the remodeling of a somatic cell, thymocyte nucleus fused
      with an oocyte. His challenge of Boveri's hypothesis on the paternal inheritance
      of centrosomes spurred further research on this subject that ultimately led to
      the definition of biparentally contributed mammalian zygotic centrosomes, for
      which the only exception is found in rodents. Very early, Szollosi and his
      colleagues devoted their interest to the studies of the fate of sperm accessory
      structures after fertilization, an area that has yet to be explored at the
      molecular level, but which may have profound implications for the swiftly
      advancing field of assisted human and animal reproduction. These studies
      contributed a great deal to our current understanding of mammalian fertilization
      and still serve as an inspiration for present studies on involved mechanisms.

PMID- 9932297
TI  - Chemically enucleated mouse oocytes: ultrastructure and kinetics of histone H1
      kinase activity.
AB  - The objective of the study was to characterize the ultrastructure changes and
      biochemical mechanisms underlying the expulsion of the entire chromosome
      complement in chemically enucleated mouse oocytes. The ultrastructural studies
      demonstrated that the morphology of cytoplasts produced by etoposide
      cycloheximide treatment were indistinguishable from intact metaphase I and II
      oocytes. Moreover, polar bodies formed by chemical enucleation were in almost all
      cases completely separated from the parent cytoplast and differed from normal
      polar bodies only in their chromatin content morphology and because they
      contained a slightly higher number of cytoplasmic organelles. The mode of polar
      body formation, however, in normal and chemically enucleated oocytes differs
      substantially: spindle involvement is important for normal polar body extrusion
      but plays no part in the protracted expulsion of chromosomes during chemical
      enucleation. After etoposide-cycloheximide treatment, histone H1 kinase activity
      remains high for the ensuing 6-8 h before declining gradually to basal levels 14
      h after treatment. The expulsion of the polar body occurred only after the slowly
      declining H1 kinase activity reached basal levels. The activity of this kinase
      rose sharply to reach maximal levels within 4 h when the enucleated oocytes were
      removed from the inhibitor-supplemented medium and placed in normal medium. The
      findings in this paper indicate that cytoplasts produced by chemical enucleation
      are morphologically normal, thus suggesting that these enucleated cells are
      suitable for cloning studies. Although effective in mouse oocytes, we postulate
      that certain modifications to the enucleation technology are necessary before a
      reliable non-invasive protocol for ungulate oocytes will be available.

PMID- 9932298
TI  - Preliminary observations in in vitro development of equine embryo after ICSI.
AB  - The objective of this study was to perform intracytoplasmic sperm injection
      (ICSI) on in vitro matured equine oocytes and to improve in vitro embryonic
      development on Vero cells after activation of the microinjected oocytes with
      calcium ionophore. After maturation (23 or 40 h, 38.5 degrees C, 5% CO2), the
      cumulus-oocyte complexes were denuded, centrifuged and all oocytes exhibiting the
      first polar body were microinjected. ICSI was performed using fresh semen from
      three fertile stallions. Microinjected oocytes were activated with calcium
      ionophore A23187 (10 min, 10 microM) and cultured individually for 7 days on Vero
      cells in microdrops. In seven trials, 353 cumulus-oocyte complexes were matured
      and 103 oocytes were microinjected. Eight oocytes were sham microinjected. After
      ICSI, 85 oocytes (82.5%) survived the sperm injection procedure. Among the 76
      successfully microinjected oocytes, 52 (68%) were fertilized (two pronuclei,
      syngamy stage and cleaved ova). Sham microinjected oocytes were not activated.
      After in vitro culture, 35 ova (46%) were cleaved 2 days after ICSI and early
      embryonic development was obtained (three embryos of 23 cells, 50 cells and more
      than 80 cells) 5 to 7 days after ICSI.

PMID- 9932299
TI  - Mouse oocyte maturation: the effect of modified nucleocytoplasmic ratio.
AB  - Fully grown mouse oocytes isolated from large antral follicles and cultured in
      vitro complete their maturation up to the second metaphase with extrusion of the
      first polar body (1PB) with a 40/50 proportion (80%). When their cytoplasmic
      volume is, however, reduced before the onset of culture, the frequency of oocytes
      completing maturation gradually decreases. In the half oocytes, 66% (33/50)
      extruded 1PB, while in third oocytes the proportion was 57% (28/49) and in
      quarter oocytes no polar bodies were extruded. The time course of germinal
      vesicle breakdown was also delayed in comparison to the decreased cytoplasmic
      volume. Moreover, the isolated germinal vesicles surrounded with a thin
      cytoplasmic rim only remained intact after a prolonged culture. The full
      competence of complete maturation can be restored by fusion of an additional
      cytoplast to the manipulated nucleate parts. We postulate that a critical
      nucleocytoplasmic volume ratio is absolutely necessary for normal maturation in
      mammalian oocytes.

PMID- 9932300
TI  - The germinal vesicle of the mouse oocyte contains elements of the
      phosphoinositide cycle: what is their role at meiosis resumption?
AB  - The role of the nuclear phosphoinositide (PI) cycle during meiotic resumption in
      mouse oocytes was examined. First, using indirect immunofluorescence staining
      with specific monoclonal antibodies (mAbs) against elements of this cycle, the
      presence of inositol trisphosphate receptors (IP3Rs) (IP3R-1 or IP3R-3) or
      phosphoinositide-phospholipase (PLC) isoforms (PLC beta 1 or PLC gamma 1) was
      monitored in the germinal vesicle (GV). Using confocal laser scanning microscopy,
      we analysed the effects of the nuclear microinjection of these antibodies on both
      spontaneous nuclear calcium oscillations and meiosis resumption. Immunostainings
      showed that IP3R-1 and PLC beta 1 isoforms were both present in the GV, whereas
      IP3R-3 and PLC gamma 1 isoforms were not. The anti-IP3R-1 mAbs or the anti-PLC
      beta 1 mAbs microinjected into the GV, induced inhibition of both the nuclear
      Ca2+ oscillations and the meiotic process, whereas the anti-IP3R-3 mAbs and the
      anti-PLC gamma 1 mAbs did not. We concluded that a specific nuclear PI cycle is
      present in the mouse oocyte and meiosis resumption requires a specific nuclear
      phosphoinositide-dependent Ca2+ signal.

PMID- 9932301
TI  - Immunocytochemical characterisation of rabbit and mouse embryonic fibroblasts.
AB  - By using indirect immunofluorescence we demonstrated the localisation of
      extracellular matrix (ECM) proteins (laminin--LAM, collagen IV--COL IV,
      fibronectin--FN) and the basic fibroblast growth factor (bFGF) in rabbit and
      mouse primary embryonic fibroblasts (PEF). Proliferating mitotically arrested PEF
      (by mitomycin C) were compared in both species. The stability of protein
      expression was ascertained during the first five successive passages. In
      addition, STO cells (i.e. permanent line of irradiated mouse fibroblasts) were
      similarly analysed. Rabbit PEF showed very high extracellular staining for FN and
      a negligible cytoplasmic positivity for LAM and COL IV. A totally reversed
      staining pattern for ECM proteins was found in mouse PEF. A dense cytoplasmic
      granulation (concentrated around the nucleus) was revealed for LAM and COL IV and
      almost no reaction for FN. The staining patterns were very stable at the culture
      conditions we applied. They were maintained during the first five successive
      passages in proliferating as well as non-proliferating mouse and rabbit PEF and
      were independent of cell concentration (individually dispersed cells versus cells
      in a confluent layer). STO cells showed the same staining for ECM proteins as the
      mouse PEF, thus confirming their origin from the same animal species. Light
      granular staining for bFGF was found in the cytoplasm of proliferating and
      mitotically arrested rabbit and mouse PEF and STO cells. The differences in
      expression of ECM proteins between the rabbit and mouse PEF, as well as the
      synthesis of bFGF, should be taken into consideration when these cells are used
      in vitro as a feeder layer for various cells (e.g. embryonic stem cells).

PMID- 9932302
TI  - [New therapeutic strategies for multiple sclerosis: unanswered questions].

PMID- 9932303
TI  - The neuropathology of adult HIV infection.
AB  - Since the onset of the acquired immune deficiency syndrome (AIDS) epidemic
      fifteen years ago, much has been learned about the effects of the human
      immunodeficiency virus (HIV) in the nervous system. This review summarizes the
      pathology findings in the central nervous system (CNS). There is now abundant
      evidence that HIV can infect the CNS directly, leading to a characteristic HIV
      encephalitis (HIVE) which occurs in 10-50 p. 100 of AIDS autopsy series.
      Multinucleated giant cells are the pathognomonic feature of HIVE and are found
      predominantly in the central white matter and deep grey matter. Evidence of
      productive HIV infection in the CNS is confined to cells of the
      microglial/macrophage lineage, from which the giant cells are almost certainly
      derived. These cells are known to express both CD4 and beta-chemokine receptors,
      which act in conjunction to permit HIV entry. Restricted infection of astrocytes
      has also been identified by a variety of methods. HIVE is frequently associated
      with white matter damage ranging from inflammatory (microglia, macrophages and
      sparse lymphocytes) to degenerative (myelin loss and axonal damage) pathology.
      Although giant cells are seen less frequently in neocortical grey matter,
      significant neuronal loss has been established in a number of studies. Recent
      investigations using markers of apoptosis, (including TUNEL, Bcl-2 and BAX), have
      established the presence of DNA damage in some neurons and in other cell types.
      Axonal damage has also been confirmed by evidence of amyloid precursor protein
      expression. The CNS is also vulnerable to opportunistic infections and high grade
      B-cell lymphomas as a result of the immune suppression of advanced HIV infection.
      Cytomegalovirus (CMV) infection is reported in 10-30 p. 100 of AIDS cases at
      autopsy, toxoplasma in 10-25 p. 100, progressive multifocal leucoencephalopathy
      in about 5 p. 100 and lymphomas, usually primary, in up to 10 p. 100. A wide
      variety of other infections has also been reported. These may coexist with HIVE
      and may be difficult to diagnose in life. CMV gives rise to microglial nodular
      encephalitis, ventriculitis, necrotising encephalitis and myelo-radiculitis.
      Presymptomatic HIV positive patients do not show HIVE or opportunistic infections
      or lymphomas in the CNS. They frequently display a low-grade T-cell infiltrate in
      the leptomeninges and parenchyma, particularly around vessels. This lymphocytic
      infiltrate has been attributed to presumed early invasion of the CNS by HIV
      although the exact timing of entry is uncertain. It is possible that reported
      abnormalities in presymptomatic cases such as gliosis, microglial activation and
      rising proviral load may anticipate the onset of HIVE but most studies show that
      significant CNS damage and HIV-related pathology is confined to patients with
      AIDS. HIV-related pathology in the spinal cord includes not only HIV myelitis,
      opportunistic infections and lymphomas, but also vacuolar myelopathy (VM) which
      affects predominantly the dorsolateral white matter tracts. The cause of VM is
      not understood and has not been unequivocally linked with HIV infection. It is
      noted that none of these neuropathological features (including HIVE) correlates
      exactly with the clinical expression of AIDS-related dementia (ARD). The exact
      contribution of macrophage activation and cytokine release, astrocytic infection,
      neuronal loss and axonal damage to the neuropsychiatric syndromes of advanced HIV
      infection remain to be determined. While the current understanding of the
      pathogenesis of HIVE and ARD is beyond the scope of this review it is axiomatic
      that accurate documentation of neuropathology findings will help to resolve the
      outstanding dilemmas relating to HIV infection of the CNS. There is considerable
      optimism that progress in therapeutic regimes for HIV-infected patients will
      succeed in eliminating the virus from the blood and from lymphoid tissue.
      (ABSTRACT TRUNCATED)

PMID- 9932304
TI  - [Pathophysiology of HIV-1 infection of the nervous system and AIDS- related
      dementia].

PMID- 9932305
TI  - [Cognitive disorders in AIDS: clinical, virological and neuroradiological
      features].
AB  - HIV-associated neurocognitive disorders are mainly reported during the late
      stages of the disease, in deeply immunosuppressed patients Clinically, they
      present as a subcortical cognitive impairment, dominated by reduced psychomotor
      speed and memory deficit. Encephalic magnetic resonance imaging shows in most
      cases a diffuse leucoencephalopathy, and there is often a poor correlation
      between clinical status and neuroradiological findings. The diagnostic and
      prognostic value of HIV load in blood and cerebrospinal fluid is currently under
      investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia
      remains uncertain.

PMID- 9932306
TI  - [Neurological complications of HIV-1 infection in an infant born to a
      seropositive mother].

PMID- 9932307
TI  - [Significance of single photon emission computed tomography and akinetic mutism].
AB  - Akinetic mutism is a reactive status with permanent opening of the eyes. The
      accountable lesions are always bilateral. The injured cerebral structures include
      the frontal gyri, the thalami or the mesencephalic areas. In one case of a 44
      year-old patient, magnetic resonance imaging and computed tomography were not
      contributive. Tc99m brain SPECT imaging was performed and displayed bilateral
      frontal hypoactivity. This case suggests that this technique could be helpful for
      diagnosis when clinical features and radiological pattern are opposite.

PMID- 9932308
TI  - [Cyst of the conus masquerading as motor neuron disease].
AB  - We report on a patient presenting with rapidly progressive painless paraplegia,
      amyotrophy and fasciculations masquerading as motoneuron disease. There were no
      bowel or bladder involvement but the patient noted mild paresthesia on the
      external part of the right foot and hypertrophy of the right calve was present.
      While lumbar CT Scan was normal, MRI showed a large cyst of the conus. Analysis
      of the cyst concluded to a benign cyst of the conus. Paraplegia resolved after
      surgery and after one year, no relapse was observed so that an hidden ependymoma
      appeared unlikely.

PMID- 9932309
TI  - [Motor neuropathy, putamen necrosis and optic nerve atrophy after acute methanol
      poisoning].
AB  - Optic neuropathy and putaminal necrosis are the most common sequellae of methanol
      poisoning. We report a case in a patient with a chronic motor neuro(no)pathy in
      addition to these neurological complications. Peripheral nerve and spinal cord
      disorders, related to methanol poisoning, are uncommon and probably
      underestimated.

PMID- 9932310
TI  - Understanding women in pain. New pathways suggested by Umea researchers:
      qualitative research and feminist perspectives.
AB  - A substantial proportion of GPs' patients are women who suffer from "unexplained"
      pain conditions, often from the musculoskeletal system. Few medical findings are
      revealed, although the symptoms lead to extensive suffering and disability. Two
      experienced Swedish GPs, Katarina Hamberg and Eva E Johansson, took their own
      frustration as their point of departure to explore the expectations, experiences,
      family lives and working lives of women who were sick-listed due to chronic
      musculoskeletal pain. Their doctoral dissertations, defended at the University of
      Umea in September this year, are based on a qualitative interview study with 20
      women aged 21-61 years. Johansson and Hamberg found that when seeing a doctor,
      the women expect to be seen, heard and taken seriously, to get information and
      time for discussion with the doctor, and to receive help and support over time.
      However, they experienced being ignored, disregarded and rejected. Symptom
      perception was characterized by loss of control and feelings of threat and
      unpredictability. The women believed that the pain had a bodily origin triggered
      by various mechanisms such as heavy and monotonous work, environmental
      influences, tensions and worries, rightful punishment or heritage. The Swedish
      study showed that family considerations had a strong impact on organizations and
      priorities in paid work. In this sample of working class women, family
      orientation strengthened and works aspiration declined in a situation of pain and
      sick leave. Problems related to rehabilitation could be explained by looking more
      closely on home conditions, especially the unwritten deal among the woman and her
      partner regarding the division of duties and power structure--the marital
      contract. Experiences of abuse and violence were reported to Hamberg and
      Johansson by several women, most of them considering this to be one root of their
      pain and ill health. The women emphasized that an understanding doctor would ask
      about violence, apprehend the hints, confirm that it was acceptable to talk about
      it, and avoid the questioning and blame that easily might increase the woman's
      feelings of guilt.

PMID- 9932311
TI  - Physicians as gatekeepers: will they contribute to restrict disability benefits?
AB  - OBJECTIVE: To study how general practitioners (GPs), specialists, and National
      Insurance Administration (NIA) medical consultants reacted to the narrowed
      eligibility criteria for disability benefits in Norway from 1991. DESIGN: Records
      of first-time applicants for disability benefits from the first quarters of 1990
      and 1993 were analysed for proposals from the physicians in relation to the
      decision. SETTING: Two Norwegian counties, Ostfold and More and Romsdal.
      SUBJECTS: 668 applicants--half the granted cases, and all the refused ones.
      RESULTS: The number of applicants fell by 39% from 1990 to 1993 and the refusal
      frequency increased from 8 to 21%. Nevertheless, GPs recommended refusal to about
      the same extent as before, 8-9% of all cases, with probably a minor fall from 52
      to 42% of the refused ones (p = 0.19). Specialists did not recommend more
      refusals than the GPs. Cases evaluated by the NIA medical consultants increased
      from 29 to 41%, and their concordance with the patients' GPs seemed to be
      approximately 50%. GPs did not give more detailed medical descriptions in 1993
      than in 1990, and discussed eligibility criteria but slightly more
      comprehensively. CONCLUSION: GPs are willing to act as gatekeepers for social
      insurance benefits for their patients, also when eligibility criteria become
      restricted.

PMID- 9932312
TI  - General practitioners' knowledge of their patients' socioeconomic data and their
      ability to identify vulnerable groups.
AB  - OBJECTIVE: To explore general practitioners' knowledge of their patients'
      socioeconomic data and their ability to identify vulnerable groups. DESIGN: A
      multipractice survey of consecutive adult patients consulting general
      practitioners during one regular workday. Doctors and patients independently
      completed mirrored questionnaires. SETTING: A geographically defined population
      of patients and doctors in Buskerud county, Norway. SUBJECTS: 1401 patients
      attending 89 general practitioners during the last two weeks of March 1995. MAIN
      OUTCOME MEASURES: The doctors' ability to state the patients' socioeconomic
      situation correctly using sensitivity and specificity. Results for patients
      scarcely and well known to the doctors are compared. RESULTS: Sensitivity ranged
      from 0.93 for work as main income source to 0.04 for not having WC/bathroom
      inside the dwelling. Specificity ranged from 1.00 for several factors to 0.73 for
      low educational level. Information on household composition and income source was
      correct for more than half of patients scarcely known to the doctors.
      CONCLUSIONS: General practitioners' knowledge of various socioeconomic data of
      their patients differs substantially and are collected at different stages in the
      relationship. Among socioeconomic data defining vulnerable groups, the patients'
      self-perceived work disability is the variable general practitioners are best at
      evaluating.

PMID- 9932314
TI  - Dyspepsia in general practice in Denmark. A 1-year analysis of consulters in
      general practice.
AB  - OBJECTIVE: To estimate the incidence rate of patients with dyspepsia in general
      practice, related to age, gender and dwelling and to classify the patients into
      dyspepsia subgroups. DESIGN: In a background population of 123,610 persons under
      the National Health Insurance System a systematic, prospective registration of
      dyspepsia patients consulting in general practice was done. Each patient was
      subject to a structured interview covering 18 dyspepsia symptoms and six alarm
      symptoms. A diagnostic chart was used to classify the patients into subgroups.
      SETTING: General practice: 93 general practitioners in 63 centres in Denmark.
      PATIENTS: Patients consulting the general practitioner with dyspepsia as their
      main complaint. RESULTS: 4215 dyspepsia patients were registered within 1 year.
      The annual incidence rate of dyspepsia was 3.4%. Alarm symptoms were present in
      11.7% of the patients. The highest incidence rates were related to middle age,
      female gender and rural dwelling. Of these 34% had dysmotility-like, 30% had
      reflux-like, 17% ulcer-like and 3% uncharacteristic dyspepsia, while 16% were
      classified into two or more groups. Dysmotility-like dyspepsia was predominant in
      women and reflux-like dyspepsia was predominant in men. CONCLUSIONS: Within 1
      year 34 patients out of 1000 will seek medical advise in general practice with a
      new episode of dyspepsia. Based on the registration of symptoms 28 of 34 can be
      classified into a single subgroup of dyspepsia; 4 of 34 patients will present
      with one or more alarm symptom.

PMID- 9932313
TI  - "Feeling your large intestines a bit bound": clinical interaction--talk and gaze.
AB  - OBJECTIVE: To explore the relationship between observation and talk in the
      clinical encounter, using the medical gaze as a key metaphor. DESIGN: A
      qualitative case study approach based on data from one consultation. Two
      sequences of patient-doctor interaction are the basis of a theoretical discussion
      of the medical gaze. SETTING: Audiotape recording from a Norwegian general
      practice. RESULTS: The doctor balances observation and talk to produce an
      appropriate, but not necessarily the only correct diagnosis. Verbal utterances
      illustrate how the doctor's structuring of the diagnosis works as an
      interactional means both to take care of the patient and to explain his
      sufferings. CONCLUSION: Clinical medicine is talk and gaze as an integral whole.
      Doctors not only make a diagnosis, but also structure a clinical reality.

PMID- 9932315
TI  - White coat hypertension in a general practice. Prevalence, cardiovascular risk
      factors and clinical implications.
AB  - OBJECTIVE: To examine the prevalence of white coat hypertension (WCH) and white
      coat effect (WCE) in a general practice. Background and biochemical
      characteristics, triglycerides, total cholesterol, HDL cholesterol, fasting blood
      glucose, microalbuminuria, ECG, smoking habits, height and weight of patients
      with white coat hypertension were compared to patients with sustained
      hypertension. DESIGN: Blood pressure measurements among mild hypertensives in
      clinic visits by doctor and at home by the patients. SETTING: A primary health
      centre in Oslo, Norway. SUBJECTS: Sixty-eight patients with mild hypertension (41
      females and 27 males) aged 20-75 years. MAIN OUTCOME MEASURES: Patients had their
      blood pressure measured in clinic visits by general practitioners and by
      themselves at home to study the prevalence of WCH and the WCE. WCH was defined as
      a consistently increased blood pressure in the clinic and a normal home-measured
      blood pressure. WCE was defined as a difference in mean systolic blood pressure
      measured by physician and patients of 10 mmHg, or more. An individual risk score
      for myocardial infarction was calculated. Subjects with and without WCH/WCE were
      compared in relation to background characteristics and biochemical differences.
      RESULTS: Fourteen patients (21%) were found with WCH, while 25 (37%) had WCE.
      Patients with WCH differed significantly from hypertensives in age, total
      cholesterol, and heart rate. In multivariate analysis, increasing age and heart
      rate were significant negative predictors for WHC. CONCLUSION: WCH may be a
      significant clinical challenge in general practice, especially among younger
      patients.

PMID- 9932316
TI  - Population-based audit of non-insulin-dependent diabetic patients aged under 65
      years in primary health care.
AB  - OBJECTIVE: To audit treatment of non-insulin-dependent diabetes mellitus (NIDDM).
      DESIGN: Cross-sectional, descriptive, population-based study. SETTING: Primary
      health care. SUBJECTS: NIDDM patients aged under 65 years in Mikkeli District, in
      eastern Finland. RESULTS: Of 381 (220 men) eligible NIDDM patients, 260 (141 men)
      participated (68%). Of subjects with at least two fasting blood glucose values >
      or = 6.7 mmol/l, diabetes diagnosis had been set to 63%. Eighty seven per cent
      had been annually checked up, and 36% had a satisfactory (< 7.5%) glycosylated
      haemoglobin A1c. Retinopathy, neuropathy and occasional microalbuminuria were
      detected in 13, 59 and 32% of patients, respectively. Patient education had been
      given to 85% of patients by the diabetes nurse. Of the patients, 79% were
      satisfied with the quality of diabetes education and care. MAIN OUTCOME MEASURES:
      Diagnostics of hyperglycaemia, regularity and continuity of care, metabolic
      control, complications, patient education and satisfaction. CONCLUSIONS: The
      metabolic control was poor among NIDDM patients in the study area. The
      diagnostics, regularity of care and the treatment of hyperglycaemia should be
      improved. Nevertheless, most patients were satisfied with both diabetes care and
      patient education.

PMID- 9932317
TI  - Neuropathy in non-insulin-dependent diabetes mellitus. The significance of
      symptoms.
AB  - OBJECTIVE: Clinical evaluation of significance of symptoms suggestive of
      neuropathy in non-insulin-dependent diabetics in general practice. DESIGN: Case
      control study. Interviewer-administered questionnaire. Physical examination by
      general practitioner researcher. SETTING: Government family practice clinic in
      Singapore. SUBJECTS: 55 patients with non-insulin-dependent diabetes (NIDDM) aged
      35-84 years (51% males), and 53 non-diabetic controls matched for age (+/- 5
      years) and gender. MAIN OUTCOME MEASURES: Proportions of subjects with presence
      of symptoms and physical signs. RESULTS: More patients than controls experienced
      symptoms suggestive of distal neuropathy (paraesthesiae: 13 vs. 4%), and lower
      extremity proximal myopathy (weakness climbing stairs: 42 vs. 19%, getting up
      from squatting position: 31 vs. 11%). No difference in proportions of patients
      and controls experiencing symptoms suggestive of autonomic neuropathy. More
      patients than controls had absent tendon reflexes (35 vs. 13%) and weaker hip
      muscles (24 vs. 6%). Of all who experienced symptoms indicating peripheral
      neuropathy, 36% of patients had absent tendon reflexes, compared with 8% of
      controls; and of those who experienced weakness of hip muscles, 31% of patients
      and 12% of controls had diminished power in the hip muscles. CONCLUSION: Symptoms
      suggestive of diabetic neuropathy are common and should be asked about in the
      routine follow-up of patients with diabetes. Up to a third of patients with
      symptoms will have clinical signs of diabetic neuropathy.

PMID- 9932318
TI  - Can the Tono-Pen replace the Schiotz tonometer in general practice?
AB  - OBJECTIVE: To study if the Tono-Pen, a hand held digital tonometer, can replace
      Schiotz tonometry in general practice. DESIGN: Tonometry with Tono-Pen and
      Schiotz tonometer were compared. SETTING: Group practice with two general
      practitioners (GPs). PATIENTS: 48 consecutive patients over 40 years of age. MAIN
      OUTCOME MEASURES: The mean difference between intra ocular pressure (IOP)
      measured with the two methods with 95% confidence intervals and 95% limits of
      agreement between them. RESULTS: One observer found a mean difference between
      methods of 0.3 mmHg and 95% limits of agreement of +/- 4 mmHg. The other observer
      with a different Schiotz tonometer, had a mean difference of approximately -2
      mmHg and 95% limits of agreement from -8 to +4 mmHg. CONCLUSION: We consider the
      Tono-Pen to be an alternative to Schiotz tonometry. The maximum mean difference
      between the methods for one GP, 1.9 mmHg, was within clinically acceptable
      limits. Possible reasons for the different agreement for the two observers are
      discussed.

PMID- 9932319
TI  - Social and depressive stress suffered by spouses of patients with mild dementia.
AB  - OBJECTIVE: To identify stressors and their correlates in spouses of patients with
      mild dementia. DESIGN: Retrospective study of patient records. SETTING: Patients
      attending a Memory Clinic at Ullevaal Hospital in Oslo. SUBJECTS: 92 mildly
      demented patients living at home (mean age 75.7 years, 51% women, mean MMSE score
      22.3) and their spouses. MAIN OUTCOME MEASURES: Frequency and types of stress
      suffered by spouses using validated and factor-analyzed instruments as measures.
      RESULTS: Twenty-five per cent or more of the spouses reported often/always having
      problems with the following: being depressed by the situation, having
      difficulties getting away on holiday, social life being affected, household
      routines being upset, and sleep being interrupted. Factor analysis of the Greene
      Caregiver Stress Scale (15 items) identified two factors; 'Social stress' and
      'Depressive stress'. Social stress was associated with the patient's I-ADL level,
      and depressive stress with mood and behaviour of the patient. The depressive
      symptomatology of the patient as expressed by the spouses was related to both
      depressive and social stress, whereas cognitive function, as measured by the
      MMSE, was not an independent predictor of carer strain. CONCLUSION: Even in
      mildly demented patients, symptoms of carer stress are frequent. Supportive
      strategies such as early diagnosis, information for carers and intervention
      strategies are discussed.

PMID- 9932320
TI  - A multidisciplinary clinical study of patients suffering from illness associated
      with release of mercury from dental restorations. Medical and odontological
      aspects.
AB  - OBJECTIVE: To describe medical and odontological aspects of patients who believed
      their illness was caused by mercury in dental fillings. DESIGN: Comparison of
      self-reported and assessed medical and odontological variables. SETTING: The
      School of Dentistry, Karolinska Institute. SUBJECTS: Sixty-seven patients,
      referred for suspected side-effects of mercury in dental fillings, and 64 matched
      controls. MAIN OUTCOME MEASURES: Incidence of medical and odontological
      diagnoses, own perception of health, and incidence of self-reported symptoms.
      RESULTS: Three quarters of the patients were women. The mean age was 49 years.
      Thirty-seven patients (55%) and 47 controls (73%) (NS) showed no sign of somatic
      disease. Half of the patients felt ill or very ill at the time of the
      examination. Patients reported twice as many symptoms as the controls during a 3
      month period. Patients reported a higher prevalence of very low resting saliva
      secretion rate, and a higher number of decayed tooth surfaces and of instances of
      temporomandibular joint dysfunction. CONCLUSION: Patients' feelings of ill-health
      were more likely related to psychiatric than somatic diagnoses. This study
      underlines the importance of making an overall diagnosis, including both mental
      and somatic disorders, especially in unclear cases and in self-diagnosed
      illnesses.

PMID- 9932321
TI  - Anatomic basis of the anterior surgery on the cervical spine: relationships
      between uncus-artery-root complex and vertebral artery injury.
AB  - Vertebral artery injury is a serious complication during anterior surgery on the
      cervical spine. However, little information is available in the literature
      concerning the mechanism of vertebral artery laceration during the procedures of
      the anterior cervical decompression. In the current study twenty-eight cadavers
      were dissected to determine the location and relationships of the fibro
      ligamentous tissues to the uncinate process, vertebral artery and nerve roots
      from the C3 to C6 levels. The vertebral artery and nerve root are encased by a
      fibro-ligamentous band at the level of the intertransverse space. This fibro
      ligamentous band is attached to the lateral aspect of the uncinate process and
      uncovertebral joint, which combines the vertebral artery, nerve root and uncinate
      process to form a complex or unit. The fibro-ligamentous tissues between the
      uncovertebral joint and vertebral artery may explain the propensity to vertebral
      artery laceration during resection of the uncinate process or an osteophyte
      projecting from the uncovertebral joint. For this reason, the authors recommend
      that before resection of the uncinate process or uncovertebral joint is
      performed, it is necessary to thoroughly dissect the fibro-ligamentous tissues
      off the uncinate process.

PMID- 9932322
TI  - Territories of the perforating (lenticulostriate) branches of the middle cerebral
      artery.
AB  - The territories of the central branches of the middle cerebral artery (MCA) were
      examined in 21 injected human brains. It was noted that these central arteries
      supplied: the caudate nucleus (dorsolateral half of the rostral part of its head;
      the entire caudal part of the head; the body and rostral portion of the tail in
      some cases), the putamen (dorsolateral part of its rostral portion, the remainder
      of the putamen, except the most caudal part occasionally), the globus pallidus
      (the entire lateral segment, except the ventrorostral and, sometimes, the most
      caudal part), the basal forebrain (lateral parts of the basal nucleus of Meynert
      and the nucleus of the diagonal band, as well as fiber bundles in this region),
      the internal capsule (dorsal and ventrocaudal part of the anterior limb, dorsal
      part of the genu, dorsal and ventrorostral part of the posterior limb), the
      corona radiata (a narrow strip close to the internal capsule) and the cerebral
      cortex (the caudal orbitofrontal cortex occasionally). The presented data may
      have certain neuroradiologic, neurologic and neurosurgical significance.

PMID- 9932324
TI  - Effects of freezing on the biomechanics of the intervertebral disc.
AB  - Storage of anatomic specimens is possible only if there is a reliable method for
      preservation of the tissues. The establishment of such a procedure is thus of
      twofold importance: clinical (transplantation of segments of the vertebral
      column) and experimental (research and teaching programs). Simple freezing at -18
      degrees C is the simplest and least expensive method for storing spinal specimens
      compared to other modes of storage such as cryo-preservation and lyophilization.
      Does this mode of storage affect the biomechanics of frozen anatomic specimens,
      in particular those of the intervertebral disc? This experiment dealt with the
      comparative biomechanical analysis before and after three months of freezing of
      19 segments of the sheep vertebral column (4 functional C4-C5 units, 3 C7-T1
      units, 6 T13-L1 units and 6 L5-L67 units). The results showed that there was no
      significant difference (risk of error 5%) between frozen and fresh segments of
      vertebral column in terms of amplitude and rigidity, except for the C7-T12
      segment where the conditions of validity of the statistical tests were not met.
      The results of this experiment allowed us to validate a biomechanical model to
      assay the effects of freezing.

PMID- 9932325
TI  - Histomorphometry of the ulnar nerve and of its branches.
AB  - A morphometric study has shown that 10% of the fibers of the ulnar nerve should
      suffice to reinnervate the biceps muscle in brachial plexus palsies. The aim of
      this study was to evaluate, by a morphometric study using computerized
      microanalysis, the cross-sectional surface areas of the different collateral and
      terminal branches of the ulnar nerve. This was expressed in terms of percentage
      of the cross-sectional surface area of the main trunk of the ulnar nerve. The
      study revealed that the branch to the flexor digitorum profundus bellies to the
      ring and little fingers formed 9.5% of the cross-sectional area of the ulnar
      nerve. Thus use of these fascicles destined for the flexor digitorum profundus,
      identified by intra-operative nerve stimulation, at the level of the arm would be
      sufficient for neurotisation of the nerve to the biceps. This has been confirmed
      by the initial clinical results in patients operated upon using this technique.

PMID- 9932323
TI  - Arterial patterns in the thoracic and abdominal segments of the esophagus:
      anatomy and clinical significance.
AB  - Cadaver studies were made to obtain more details about the arterial patterns in
      the thoracic and abdominal segments of the esophagus, with emphasis on the
      arterial supply to the lower esophageal sphincter (LES). The results showed that
      the inferior thoracic segment of the esophagus usually received blood supply from
      a single artery, with an average diameter of 1.42 +/- 0.49 mm (X +/- s), whereas
      the abdominal segment was commonly supplied by two arteries. The abdominal
      esophageal arteries coming from the left gastric artery were semi-circular in
      shape with an average diameter of 2.06 +/- 0.70 mm. From these semi-circular
      esophageal arteries, 3 to 8 smaller arteries branched off and penetrated into the
      muscle of the abdominal segment of the esophagus or anastomosed with arterial
      branches from the inferior thoracic segment. Thus, the blood supply of the
      abdominal segment was richer than that of the inferior thoracic segment. This
      richness of blood supply, characterized by semicircular esophageal arteries in
      the abdominal segment, may be important for the function of the LES.

PMID- 9932326
TI  - The suspensory ligament of the penis: an anatomic and radiologic description.
AB  - The suspensory system of the penis acquires clinical importance in reparative
      surgery, traumatology and through its role in erection. The aim of this study was
      to identify the different anatomic structures constituting the suspensory
      ligament by dissection and by magnetic resonance imaging (MRI). Ten unembalmed
      male subjects were used for dissection of the region of the base of the penis.
      Ten volunteer patients underwent MRI of the penis before and after the injection
      of prostaglandin (PGE1). The suspensory apparatus consisted of separate
      ligamentous structures: the fundiform ligament, which is lateral, superficial and
      not adherent to the tunica albuginea of the corpora cavernosa; the suspensory
      ligament properly so-called, further back, stretching between the pubis and the
      tunica albuginea of the corpora cavernosa and consisting of two lateral,
      circumferential, and one median bundles, which circumscribed the dorsal vein of
      the penis. These structures were identifiable in MRI and their supporting role
      was evidenced during tests of erection. The suspensory ligament seemed to
      maintain the base of the penis in front of the pubis and to behave as a major
      point of support for the mobile portion of the penis during erection.

PMID- 9932327
TI  - The lateral calcaneal artery.
AB  - An anatomic study of the lateral extraosseous and intraosseous arterial supply of
      the calcaneus and the lateral soft tissue was carried out on 10 fresh lower adult
      cadaver legs using different anatomic and radiologic procedures (plastination,
      modified Spalteholz clearing technique, digital subtraction and rotational
      angiography and computed tomographic angiography). Consistent patterns of
      extraosseous and intraosseous lateral calcaneal vascular anatomy were
      demonstrated. The lateral calcaneal artery is a branch of the anterior tibial
      artery which crosses over the calcaneal tuberosity and forms a large lateral arch
      with the lateral tarsal artery which is a branch of the dorsalis pedis artery.
      The intraosseous circulation is supplied laterally by the lateral calcanear
      artery, medially via the short branches of the lateral plantar artery. Comparing
      magnet resonance images after fresh calcaneal fractures the lateral calcanear
      artery may be interrupted by the impacted lateral bulge, by the conventional
      lateral surgical approach, or by applying a lateral osteosynthesis plate. This
      may cause avascular bone necrosis. Furthermore the lateral calcanear artery can
      clinically serve as a vascular pedicle for a local rotational skin flap to cover
      soft tissue defects of the heel.

PMID- 9932328
TI  - Variations of relative anteversion of the femoral neck during walking.
AB  - Based on the geometric model developed by Netter [11], we determined the
      different positions of the femoral neck during monopodal support in walking in
      relation to a fixed frontal plane of reference (relative anteversion). This
      "relative anteversion" ranges on average from 24 degrees of retroversion at the
      beginning of support to 15 degrees of anterversion at the end if loading. We then
      studied the relations possibly existing between relative anteversion and
      acetabular orientation on the one hand, and the orientation of the resultant of
      the articular stresses on the other (both being variables during monopodal
      support in walking). The results showed that relative anteversion is well
      correlated with variations of position of the acetabulum since, at most, the
      deviation between the respective axes did not exceed the anatomic deviation due
      to absolute anteversion of the femoral neck and acetabulum. Lastly, analysis of
      the relations obtained with the orientation of the resultant of the articular
      stresses allowed a better comprehension of the functional distribution of forces.

PMID- 9932329
TI  - Sacrococcygeal and transsacral epidural anesthesia in the laboratory pig: a model
      for experimental surgery.
AB  - The laboratory piglet is currently the preferred animal for experimental
      digestive surgery. In order to ensure optimal perioperative analgesic control
      with motor blockade during surgery together with rapid postoperative recovery,
      epidural anesthesia techniques were developed in this animal. We report the
      anatomo-radiologic studies (10 animals) and clinical experiments (51
      transplantations of the liver and the small intestine) which led to the
      refinement of this anesthesia. In laboratory piglets, epidural anesthesia by
      distal transsacral (S4-S5) or sacrococcygeal approach is possible in a
      reproducible manner. The localization of the injection site is simple and
      epidural space catheterisation is easy without risk for the dural sac which ends
      at S1-S2.

PMID- 9932330
TI  - High-resolution computed tomography of the canals of the temporal bone: anatomic
      correlations.
AB  - The aim of this study was to define precisely the imaging of the canals of the
      temporal bone by means of high-resolution computed tomography (HR CT). Based on
      24 temporal bones removed from embalmed cadavers and investigated with HR CT,
      several canals were studied: the canal of the chorda tympani (CdT), the canal of
      the auricular branch of the vagus nerve (ABV), the canal of the tympanic nerve,
      the canal of the carotico-tympanic nerve and that of the lesser petrosal nerve.
      Anatomic correlations for six temporal bones were made to confirm the validity of
      our radiologic hypotheses. In CT, in axial sections OM 0 degree, the posterior
      canal of the CdT was visualized in 71% of cases, the ABV canal in 4%, the
      inferior tympanic canal in 12.5%, the carotico-tympanic canal in no cases and the
      canal of the lesser petrosal nerve in 50% (and in 75% with an incidence of OM +
      10 degrees). In coronal incidence, the posterior canal of the CdT was seen in 20%
      of cases, the ABV canal in 25%, the inferior tympanic canal in 85%, the
      caroticotympanic canal in 65% and that of the lesser petrosal nerve in 15%. The
      six anatomic comparisons confirmed the radiologic hypotheses in every case. These
      different structures are easy to identify in HR CT and are important to define so
      that any lesion (tumoral or vascular) developing in their vicinity may not be
      overlooked.

PMID- 9932331
TI  - The arterial blood supply of the pancreas: a review. V. The dorsal pancreatic
      artery. An anatomic review and a radiologic study.
AB  - The present article is the fifth part of a comprehensive review on the arterial
      blood supply of the pancreas and deals with the dorsal pancreatic artery. The aim
      of this review is to summarise the anatomic studies, starting from Haller's
      reports, and to supply, as far as possible with original material, angiographic
      evidence for the classic anatomic notions. For this purpose, the overall research
      was carried out by studying 1015 selective angiographies (celiac trunk and its
      branches, superior mesenteric artery) taken from the angiographic archives of the
      Institutes of Radiology of Siena, Rome (Catholic University), and Perugia.
      Angiographically, the authors could demonstrate the dorsal pancreatic artery,
      present in most instances, as arising from the splenic artery, common hepatic
      artery, superior mesenteric artery or celiac trunk and accessory right hepatic
      artery as coming from the superior mesenteric artery. Variations in the course
      and length of the dorsal pancreatic artery were demonstrated as well as some
      collateral branches. The authors underline the discordant opinions still existing
      regarding the incidence of the different ways the dorsal pancreatic artery
      arises, and discuss its uncertain embryologic development and surgical relevance.

PMID- 9932332
TI  - An anomalous digastric muscle with three accessory bellies and one fibrous band.
AB  - During our routine dissection studies we encountered an anomalous digastric
      muscle with three accessory bellies and one fibrous band in one embedded cadaver.
      All of these structures were attached to the mylohyoid raphe. This anomaly should
      be considered during surgical procedures involving this region.

PMID- 9932333
TI  - Approximating dipoles from human EEG activity: the effect of dipole source
      configuration on dipolarity using single dipole models.
AB  - Dipolarity is the goodness-of-fit of the observed potential distribution with one
      calculated using specific assumptions about the source of the electrical
      potential distribution. We used computer simulations to examine the effect of
      different distributions of sources on their resulting dipolarity values. Electric
      dipoles were placed in a head-shaped model with uniform conductivity using four
      different dipole configurations (randomly oriented dipoles, a uniform dipole disk
      layer, a dipole disk layer with uniformly distributed holes, or one with randomly
      oriented dipoles). The best-fitting single dipole for each configuration was
      calculated and the dipolarity was computed as the mean squared error of the
      electrical potential distributions generated by the actual dipole configuration
      and by the best-fitting single dipole. The simulations show that: 1) a smooth
      dipole layer with or without holes gives dipolarities above 99.5% even when
      extended over areas as large as 1256 mm2; 2) randomly oriented dipoles under a
      smooth dipole layer also give dipolarities above 99.5%; and 3) randomly oriented
      and distributed dipoles, even if contained in a small portion of the total area,
      give dipolarities below 93.0%. These simulations show that inhomogeneity (holes)
      within a dipole disk layer per se do not lower dipolarity; rather, it is the
      random orientation and distribution of these dipoles which lowers dipolarity.
      Furthermore, dipolarity is not lowered by such randomly oriented and distributed
      dipoles when they are beneath a dipole disk layer.

PMID- 9932334
TI  - Glucose effectiveness and insulin sensitivity from the minimal models:
      consequences of undermodeling assessed by Monte Carlo simulation.
AB  - The unlabeled (cold) minimal model (MM) and the labeled (hot) minimal model (HMM)
      are a powerful tool to investigate in vivo metabolism from a standard intravenous
      glucose tolerance test (IVGTT) or hot IVGTT (HIVGTT). They allow to estimate
      metabolic indexes of the glucose-insulin system, namely glucose effectiveness
      (GE) and insulin sensitivity (IS) (of uptake and production those of MM, and of
      uptake only those of HMM). Here, the consequences of the single-compartment
      glucose kinetics approximation used in the MM's are investigated via Monte Carlo
      simulation, using a physiologic reference model (RM) of the system. RM allows to
      generate noisy synthetic plasma concentrations of glucose, tracer glucose, and
      insulin during IVGTT and HIVGTT, which are then analyzed with MM and HMM. The MM
      and HMM GE and IS are then compared with the RM ones. Results of 400 runs show
      that: 1) correlation of MM GE with the RM index is weak; 2) MM IS is well
      correlated with the RM index, but severely underestimates it; 3) HMM clearance
      rate is correlated with RM clearance; and 4) HMM IS is well correlated and only
      slightly overestimates the RM index. These results demonstrate that GE of MM is
      most affected by the single-compartment approximation and the indexes of HMM are
      more robust than those of MM.

PMID- 9932335
TI  - Influence of electrical coupling on early afterdepolarizations in ventricular
      myocytes.
AB  - Computer modeling is used to study the effect of electrical coupling between a
      myocardial zone where early afterdepolarizations (EAD's) can develop and the
      normal neighboring tissue. The effects of such coupling on EAD development and on
      the likelihood of EAD propagation as an ectopic beat are studied. The influence
      on EAD formation is investigated by approximating two partially coupled
      myocardial zones modeled as two active elements coupled by a junctional
      resistance R. For R values lower than 800 omega cm2, the action potentials are
      transmitted to the coupled element, and for R values higher than 850 omega cm2
      they are blocked. In both ranges of R, when the electrical coupling increases,
      the EAD's appear at more negative takeoff potentials with higher amplitudes and
      upstrokes. The EAD's are not elicited if the electrical coupling is too high. In
      a separate model of two one-dimensional cardiac fiber segments partially coupled
      by a resistance R, critical R values exist, between 42 and 54 omega cm2, that
      facilitate EAD propagation. These results demonstrate that in myocardial zones
      favorable to the formation of EAD, the electrical coupling dramatically affects
      initiation of EAD and its spread to the neighboring tissue.

PMID- 9932336
TI  - A model-based algorithm for blood glucose control in type I diabetic patients.
AB  - A model-based predictive control algorithm is developed to maintain normoglycemia
      in the Type I diabetic patient using a closed-loop insulin infusion pump.
      Utilizing compartmental modeling techniques, a fundamental model of the diabetic
      patient is constructed. The resulting nineteenth-order nonlinear pharmacokinetic
      pharmacodynamic representation is used in controller synthesis. Linear
      identification of an input-output model from noisy patient data is performed by
      filtering the impulse-response coefficients via projection onto the Laguerre
      basis. A linear model predictive controller is developed using the identified
      step response model. Controller performance for unmeasured disturbance rejection
      (50 g oral glucose tolerance test) is examined. Glucose setpoint tracking
      performance is improved by designing a second controller which substitutes a more
      detailed internal model including state-estimation and a Kalman filter for the
      input-output representation. The state-estimating controller maintains glucose
      within 15 mg/dl of the setpoint in the presence of measurement noise. Under noise
      free conditions, the model-based predictive controller using state estimation
      outperforms an internal model controller from literature (49.4% reduction in
      undershoot and 45.7% reduction in settling time). These results demonstrate the
      potential use of predictive algorithms for blood glucose control in an insulin
      infusion pump.

PMID- 9932337
TI  - Dynamic updating in DIAS-NIDDM and DIAS causal probabilistic networks.
AB  - Diabetes advisory system (DIAS) is a decision support system, which has been
      developed to provide advice on the amount of insulin injected by subjects with
      insulin-dependent diabetes mellitus (IDDM). DIAS employs a temporal causal
      probabilistic network (CPN) to implement a stochastic model of carbohydrate
      metabolism. The CPN network has recently been extended to provide also advice to
      subjects with noninsulin-dependent diabetes mellitus (NIDDM). However, due to
      increased complexity and size of the extended CPN the calculations became
      unfeasible. The CPN network was, therefore, simplified and a novel approach
      employed to generate conditional probability tables. The principles of dynamic
      CPN's were adopted and, in combination with the method of conditioning, learning,
      and forecasting, were implemented in a time- and memory-efficient way. An
      evaluation using experimental data was carried out to compare the original and
      revised DIAS implementations employing data collected by patients with IDDM, and
      to assess the a posteriori identifiability of model parameters in patients with
      NIDDM.

PMID- 9932338
TI  - Unsupervided pattern recognition for the classification of EMG signals.
AB  - The shapes and firing rates of motor unit action potentials (MUAP's) in an
      electromyographic (EMG) signal provide an important source of information for the
      diagnosis of neuromuscular disorders. In order to extract this information from
      EMG signals recorded at low to moderate force levels, it is required: i) to
      identify the MUAP's composing the EMG signal, ii) to classify MUAP's with similar
      shape, and iii) to decompose the superimposed MUAP waveforms into their
      constituent MUAP's. For the classification of MUAP's two different pattern
      recognition techniques are presented: i) an artificial neural network (ANN)
      technique based on unsupervised learning, using a modified version of the self
      organizing feature maps (SOFM) algorithm and learning vector quantization (LVQ)
      and ii) a statistical pattern recognition technique based on the Euclidean
      distance. A total of 1213 MUAP's obtained from 12 normal subjects, 13 subjects
      suffering from myopathy, and 15 subjects suffering from motor neuron disease were
      analyzed. The success rate for the ANN technique was 97.6% and for the
      statistical technique 95.3%. For the decomposition of the superimposed waveforms,
      a technique using crosscorrelation for MUAP's alignment, and a combination of
      Euclidean distance and area measures in order to classify the decomposed
      waveforms is presented. The success rate for the decomposition procedure was 90%.

PMID- 9932339
TI  - Real-time discrimination of ventricular tachyarrhythmia with Fourier-transform
      neural network.
AB  - We have developed a method to discriminate life-threatening ventricular
      arrhythmias by observing the QRS complex of the electrocardiogram (ECG) in each
      heartbeat. Changes in QRS complexes due to rhythm origination and conduction path
      were observed with the Fourier transform, and three kinds of rhythms were
      discriminated by a neural network. In this paper, the potential of our method for
      clinical uses and real-time detection was examined using human surface ECG's and
      intracardiac electrograms (EGM's). The method achieved high sensitivity and
      specificity (> or = 0.98) in discrimination of supraventricular rhythms from
      ventricular ones. We also present a hardware implementation of the algorithm on a
      commercial single-chip CPU.

PMID- 9932340
TI  - Active cancellation system of acoustic noise in MR imaging.
AB  - In this paper, we introduce a new neural-network architecture for reducing the
      acoustic noise level in magnetic resonance (MR) imaging processes. The proposed
      neural network (NN) consists of two cascaded time-delay NN's (TDNN's). This NN is
      used as the predictor of a feedback active noise control (ANC) system for
      reducing acoustic noises. Experimental results with real MR noises show that the
      proposed system achieved an average noise power attenuation of 18.75 dB, which
      compares favorably with previous studies. Preliminary results also show that with
      the proposed ANC system installed, acoustic MR noises are greatly attenuated
      while verbal communication during MRI sessions is not affected.

PMID- 9932341
TI  - ECG beat detection using filter banks.
AB  - We have designed a multirate digital signal processing algorithm to detect heart
      beats in the electrocardiogram (ECG). The algorithm incorporates a filter bank
      (FB) which decomposes the ECG into subbands with uniform frequency bandwidths.
      The FB-based algorithm enables independent time and frequency analysis to be
      performed on a signal. Features computed from a set of the subbands and a
      heuristic detection strategy are used to fuse decisions from multiple one-channel
      beat detection algorithms. The overall beat detection algorithm has a sensitivity
      of 99.59% and a positive predictivity of 99.56% against the MIT/BIH database.
      Furthermore this is a real-time algorithm since its beat detection latency is
      minimal. The FB-based beat detection algorithm also inherently lends itself to a
      computationally efficient structure since the detection logic operates at the
      subband rate. The FB-based structure is potentially useful for performing
      multiple ECG processing tasks using one set of preprocessing filters.

PMID- 9932342
TI  - Spectral analysis of periodic fluctuations in electrocardiographic
      repolarization.
AB  - Repolarization alternans (RPA) indicates alternate-beat fluctuations in the
      temporal or spatial characteristics of the echocardiogram (ECG) STU segment which
      may represent dispersion in repolarization. Spectral decomposition has revealed
      microvolt-level RPA which has been found to correlate with ventricular
      tachycardia (VT) and fibrillation, and is increasingly being used for clinical
      risk stratification. However, while interruptions in periodicity are known to
      affect spectral decomposition, their quantitative impact on RPA and its clinical
      utility have been poorly described. We therefore studied the effect of variable
      alignment, extrasystoles, dissimilar beats and beat exclusion on RPA magnitude in
      simulations and on the sensitivity and specificity of RPA for VT in a pilot
      clinical study. RPA magnitude was exquisitely sensitive to QRS alignment such
      that +/- 1 ms random beat misalignment reduced it by 68% in simulations.
      Correspondingly, suboptimal QRS alignment in clinical ECG's caused the
      sensitivity of RPA for inducible VT to fall from 93% to as low as 63%; while JT
      alignment was also less effective for RPA recovery. As an experiment in
      minimizing morphometric irregularities in clinical ECG's, we found that RPA
      magnitude actually fell when replacing either measurably dissimilar or ectopic
      beats with more representative beats. In addition, inserting or deleting beats
      also reduced RPA magnitude in clinical sequences and simulations. These
      statistical analyses suggest that the precision of beat alignment and
      interruptions to ECG periodicity, which may occur physiologically, may greatly
      reduce the clinical utility of RPA for VT. Dynamic alterations in RPA in response
      to sequence irregularities require further study before RPA may be optimally
      applied to screen for ventricular arrhythmias.

PMID- 9932343
TI  - A computational model for tracking subsurface tissue deformation during
      stereotactic neurosurgery.
AB  - Recent advances in the field of stereotactic neurosurgery have made it possible
      to coregister preoperative computed tomography (CT) and magnetic resonance (MR)
      images with instrument locations in the operating field. However, accounting for
      intraoperative movement of brain tissue remains a challenging problem. While
      intraoperative CT and MR scanners record concurrent tissue motion, there is
      motivation to develop methodologies which would be significantly lower in cost
      and more widely available. The approach we present is a computational model of
      brain tissue deformation that could be used in conjunction with a limited amount
      of concurrently obtained operative data to estimate subsurface tissue motion.
      Specifically, we report on the initial development of a finite element model of
      brain tissue adapted from consolidation theory. Validations of the computational
      mathematics in two and three dimensions are shown with errors of 1%-2% for the
      discretizations used. Experience with the computational strategy for estimating
      surgically induced brain tissue motion in vivo is also presented. While the
      predicted tissue displacements differ from measured values by about 15%, they
      suggest that exploiting a physics-based computational framework for updating
      preoperative imaging databases during the course of surgery has considerable
      merit. However, additional model and computational developments are needed before
      this approach can become a clinical reality.

PMID- 9932344
TI  - Characterization of signals and noise rejection with bipolar longitudinal
      intrafascicular electrodes.
AB  - Longitudinal intrafascicular electrodes (LIFE's) are fine electrodes threaded
      into the extracellular space between axons in peripheral nerves or spinal roots.
      We are developing these electrodes for application in functional electrical
      stimulation and in basic physiology. An area of concern in chronic recording
      application of LIFE's is the possibility of electromyogram and other external
      noise sources masking the recorded neural signals. We characterized neural
      signals recorded by LIFE's and confirmed by three independent methods that
      increasing interelectrode spacing for bipolar LIFE's increases signal amplitude.
      The spectrum of neural signal from bipolar and monopolar LIFE lies between 300 Hz
      and 10 kHz. The amplitude of the spectrum increases with increasing
      interelectrode spacing, although the distribution is not affected. Single unit
      analysis of LIFE recordings show that they record selectively from units closest
      to the electrode active site. Units with conduction velocities ranging from 50
      120 m/s were identified. Extraneural noise, as stimulus artifact or
      electromyogram, is much reduced with bipolar LIFE recording, as compared to
      monopolar recordings. Relative improvement in neural signal to extraneural noise
      increases with interelectrode spacing up to about 2 mm. Since there is no further
      improvement beyond 2 mm, we conclude that the preferred interelectrode spacing
      for bipolar LIFE's is 2 mm.

PMID- 9932346
TI  - [Professional training in medicine does not stop once one graduates from a
      department and obtains the diploma of physician].

PMID- 9932345
TI  - Fluid mechanics analysis of a spring-loaded jet injector.
AB  - A syringe jet injector is a device designed to administer a drug quickly and
      painlessly through the skin. Though syringe jet injectors have been in use for
      almost 50 years, current designs still suffer from inconsistent performance. To
      better understand the fluid mechanics of jet injection and gain insight into how
      the design might influence performance, two theoretical analyses to determine the
      fluid pressure profile at the exit orifice were conducted. The first was a
      continuum analysis assuming static incompressibility. Results demonstrated that
      the maximum jet pressure was highly sensitive to the spring constant, initial
      piston velocity, and piston cross-sectional area while the time to achieve the
      maximum pressure was most sensitive to the injection chamber length, initial
      piston velocity, bulk modulus of the injectant, and the piston cross-sectional
      area. The second analysis was a shock wave analysis. Results demonstrated a
      stepwise pressure-time plot that was similar in magnitude to that for the
      continuum analysis assuming static incompressibility. Results from these two
      investigations are useful for design modification of the jet injector to achieve
      desired pressure-time profiles at the orifice. Control of pressure-time profiles
      may help to achieve a more consistent and effective injection process.

PMID- 9932347
TI  - [HLA antigens and ocular pathology].
AB  - The HLA antigen system is a complex of genes which have the control of a lot of
      cellular receptors with high role in histocompatibility, genes which code the
      born of all molecules may play a significant role in graft reaction and in
      starting the immunologic answer. The immunological study was demonstrated that
      many ophthalmological diseases are very deep linked by the HLA antigens.

PMID- 9932348
TI  - [The synthesis and effects of nitric oxide at the retinal level].
AB  - Nitric oxide (NO) is synthetized from L-arginine by the aid of an enzyme--NO
      synthase (NOS). This enzyme has there isoforms, which are either constitutive;
      neural NOS (nNOS) and endothelial NOS (eNOS) or inducible (iNOS). These three
      isoforms are expressed also in the retina. NO produced in small amounts by nNOS
      and eNOS is involved in neurotransmission in the retina and in the regulation of
      retinal arteriolar tonicity. NO produced in large quantities by iNOS is a
      bactericidal agent but can also generate inflammation of the retina and even
      retinal degeneration.

PMID- 9932349
TI  - [Methods of preserving the cornea].
AB  - The article shows the main corneal preservation techniques used in eye banks:
      short-time corneal preservation techniques, medium-time and long-time, each of
      them with advantages and disadvantages.

PMID- 9932350
TI  - [Complications specific to posterior chamber lens implantation].
AB  - The purpose of the study is to evaluate posterior chamber intraocular lenses
      complication, causes and their prevention.

PMID- 9932351
TI  - [General anesthesia in surgical interventions in children].
AB  - The paper shows our experience about general anesthesia in children treated for
      an ophthalmologic disease in Clinic of Ophthalmology, Timisoara in the last 7
      years. We think that when the globe is opened the best anesthetic is halotan and
      ketanest is better in closed-eye surgery and ophthalmologic examination.

PMID- 9932352
TI  - [Cataract and the exfoliative syndrome].
AB  - Exfoliation syndrome is more frequently in the older age and represents a risk
      factor for cataract surgery. This paper presents the results of a clinical trial
      made on 436 patients with troubles of transparency of the lens who were
      investigate in our clinic during January 1995-January 1997, and in whom, clinic
      and paraclinic exams have not revealed any associated ocular disease. In 14% of
      these patients who presented troubles of transparency of the lens were found uni-
      or bilateral exfoliation. The authors present the treatment applied both in
      patients in clinical follow-up (50% of patients with exfoliation syndrome develop
      secondary glaucoma) and patients who underwent surgical treatment. The patients
      with exfoliation syndrome and cataract have had a high risk to develop intra- and
      postoperative complications. The surgical treatment suggested by authors is
      extracapsular cataract extraction, either or without lens implantation and
      peripheral iridectomy which represents a compulsory step.

PMID- 9932353
TI  - [Acyclovir treatment--its effect on visual acuity and the rate of recurrences in
      herpetic keratitis].
AB  - We treated a number of 141 patients suffering of herpetic keratitis--34 were
      treated with Acyclovir in the first 72 hours the symptoms started, 42 were
      treated with Acyclovir after this interval and 65 were treated with IDU. We
      compared visual acuity after six month and we proved that those that were treated
      with Acyclovir had the same or better visual performances in most cases.
      Recurrence rate was 0% in the first year and 2.94% in the second year for those
      witch were treated with Acyclovir in the first 72 hours symptoms started and
      2.94% in the first year and 14.71% in the second year for those treated with
      Acyclovir after this interval. Patients treated with IDU had suffered 23.53%
      recurrences in the first year and 41.18% recurrences in the second year.
      Acyclovir treatment and its precociousness protect patients sight and reduce
      number of recurrences.

PMID- 9932354
TI  - [Cytological criteria for assessing the evolution of herpetic keratitis].
AB  - There were studied 33 patients admitted with clinical diagnosis of superficial
      herpetic keratitis, typical form of dendritic ulcer. In all these cases there
      were performed smears from the level of cornea and conjunctiva, that were stained
      with rapid blue polycrome tanin Dragan staining method. Smears were performed
      before and during the evolution of the disease, in patients specifically treated
      with antiviral drugs and also in cases treated unspecifically. There are
      described some cytological particularities which have a relative specificity for
      the diagnosis: a high number of lymphocytes with cytoplasmic blebs, giant
      multinucleated cells, and epithelial cells with degenerative lesions
      (nucleocytoplasmic inclusions, vacuoles, chromophobe halo around nucleus). Such
      lesions were not observed in patients with non herpetic keratitis. Modifications
      noticed in epithelial corneal cells could suggest the diagnosis, which can be
      associated with clinical examination, in order to administer a specific therapy.
      Dynamic cytological evolution shows early regression of specific cellular
      modifications in patients treated by Acyclovir.

PMID- 9932355
TI  - [The effect of chronic beta-blocker treatment on the evolution of primary open
      angle glaucoma].
AB  - Comparative analysis of the results of the trabeculectomy in primary open-angle
      glaucoma (POAG) when it was chosen as a primary treatment and when was preceded
      by chronic use of topic beta-blockers. MATERIAL AND METHOD: Retrospective study
      of 59 patients (group A) with primary trabeculectomy and 42 patients (group B)
      with topic beta-blockers treatment for at least 3 years subsequent to
      trabeculectomy was performed. The average postoperative follow-up period was 3
      years and 5 months. RESULTS: Postoperative IOP lowering was similar in both
      groups; There are no statistical differences between group A and B concerning
      stationary cases (76.27% in group A and 75.4% in group B), regressive cases (6.8%
      and 7.14% respectively) and progressive cases (18.6% and 17.9% respectively);
      Preoperative and postoperative complication rates were similar in the 2 groups.
      CONCLUSIONS: The chronic beta-blockers use does not influence the evolution of
      operated POAG.

PMID- 9932356
TI  - Criteria for choosing lens implants.
AB  - Choosing the proper artificial lens can be a problem, especially for the young
      surgeons, considering the fact that the "market" is so rich in possibilities. The
      present paper analyses the lens according to their dimension, form and material,
      in a perspective based on personal experience.

PMID- 9932357
TI  - [Obstructions of the retinal artery branches--the clinical and therapeutic
      aspects].
AB  - The purpose of the study is the evaluation of the therapeutical results in
      arterial retinal branches obstructions, according their etiology and clinical
      features. The study includes 30 patients with arterial retinal branch
      obstructions, hospitalized in the Ophthalmological Department from Cluj, between
      1989-1996. The temporal branches have been significantly more frequently affected
      (73.33%), as compared to the nasal ones (6.66%). We noticed no difference in
      visual acuity's recovery according the precocity of the therapy. Visual acuity's
      recovery after the arterial retinal branches obstructions is under the
      simultaneous influence of a group of factors. In this context, the most important
      ones are: the etiopathogenetic mechanism and the degree of the arterial
      obstruction. Under these circumstances, an important consideration has to be
      given to the prophylactic component of the treatment.

PMID- 9932358
TI  - [The conservative treatment and evolution of intermittent divergent strabismus].
AB  - We study 43 children with intermittent exotropia treated in Eye Clinic, Cluj.
      83.7% shows excess divergence exotropia and only 16.3% convergence insufficiency
      exotropia. The children are treated with optical correction, prisms and
      orthoptics.

PMID- 9932359
TI  - [A recurrent adenoid-type basal-cell epithelioma of the superior portion of the
      ala nasi and of the left internal palpebral angle (rodent ulcer)--a clinical
      case].
AB  - The palpebral basocellular epithelioma is the most frequent neoformation of the
      ocular adnexa. It has a local invasive potential, necessitating a complete and
      also oncological excision. This paper presents a case in which an insufficient
      treatment has gone to the recurrence of the tumor.

PMID- 9932360
TI  - [Lacrimal gland ectopia--a clinical case].
AB  - We describe a case of lacrimal gland ectopia which was surgically excised and led
      to a dry eye syndrome. The various diagnostic confusions are listed.

PMID- 9932361
TI  - [Functional recuperation in unilateral congenital cataract--a clinical case].
AB  - The management of a monocular congenital cataract is dominated by the problems of
      amblyopia, always present. The paper shows the case of an eight years old child,
      who was operated when he was 6 month of age for monocular congenital cataract.
      After YAG-Nd treatment of secondary cataract, aerian correction and intense
      pleoptic and orthoptic treatment, the visual acuity rise up to 1/4, when was
      possible to made an IOL implantation. We consider that is important to try to
      solve the monocular congenital cataract, even at higher ages, because the results
      is possible to be satisfactorily.

PMID- 9932362
TI  - [Clinical observations of a case of anterior uveitis associated with ankylosing
      spondylitis and psoriatic arthritis. Paraclinical studies].
AB  - Ankylosing spondylitis is a rheumatic disease linked to the presence of HLA B27,
      when the most frequent eye lesion is the anterior uveitis. This lecture tries to
      systematize some clinical and laboratory investigations, necessary to establish
      etiology, trigger factors of acute episode, in the same time assuring the
      exclusion of other forms of uveitis, taking into consideration the fact the
      treatment of endogenous uveitis is based on corticotherapy with different doses
      and administration modes, according to uveitis type.

PMID- 9932363
TI  - [Orbito-ocular complications caused by paranasal sinus diseases].
AB  - On the background of 32 cases which were followed, the authors underlined the
      diagnosis and treatment difficulties in patients with latent sinusitis or with a
      torpid symptomatology, insisting upon orbito-ocular complications with
      predilection in frontal sinusitis. The authors obligate to emphasize the clinical
      and paraclinical investigations in order to elucidate the rhinosinusal causes.

PMID- 9932364
TI  - [The differential diagnosis of a prominent papilla nervi optici--the
      ophthalmoscopic and angiofluorographic aspects].
AB  - In the beginning, the paper presents an up-to-date of the theoretical concepts
      about the structure, vascularisation, ophthalmoscopical and angiographical
      appearance of the optic disc. The next part reveals the most important situations
      in which the optic disc become prominent, sustained by ophthalmoscopic and
      fluorescein angiographic images. The final part contains the practical
      conclusions.

PMID- 9932366
TI  - Calcium channels coupled to glutamate release.

PMID- 9932367
TI  - Presynaptic modulation of glutamate release.

PMID- 9932368
TI  - Properties and localization of glutamate transporters.

PMID- 9932370
TI  - Control of time course of glutamatergic synaptic currents.

PMID- 9932369
TI  - Physiological and pathological operation of glutamate transporters.

PMID- 9932371
TI  - Synthesis of glutamate and its regulation.

PMID- 9932372
TI  - Uptake of glutamate into synaptic vesicles.

PMID- 9932373
TI  - Synaptic arrangement of glutamate receptors.

PMID- 9932374
TI  - Anchoring of glutamate receptors at the synapse.

PMID- 9932375
TI  - The organization and regulation of non-NMDA receptors in neurons.

PMID- 9932376
TI  - AMPA receptors: molecular and functional diversity.

PMID- 9932377
TI  - Molecular determinants of NMDA receptor pharmacological diversity.

PMID- 9932378
TI  - Modulation of NMDA receptors.

PMID- 9932379
TI  - Metabotropic glutamate receptors and neurodegeneration.

PMID- 9932380
TI  - Intracellular calcium and magnesium: critical determinants of excitotoxicity?

PMID- 9932381
TI  - Neurodegeneration and glutamate induced oxidative stress.

PMID- 9932382
TI  - Glutamate induced cell death: apoptosis or necrosis?

PMID- 9932383
TI  - Synaptic plasticity in ischemia: role of NMDA receptors.

PMID- 9932384
TI  - Glutamate in the human brain: possible roles in synaptic transmission and
      ischemia.

PMID- 9932386
TI  - Glutamate toxicity in chronic neurodegenerative disease.

PMID- 9932385
TI  - Glutamate and its receptors in the pathophysiology of brain and spinal cord
      injuries.

PMID- 9932387
TI  - Electrophysiological substrates for focal epilepsies.

PMID- 9932388
TI  - Involvement of glutamate in human epileptic activities.

PMID- 9932389
TI  - Glutamate receptors in epilepsy.
AB  - Glutamatergic synapses play a critical role in all epileptic phenomena. Broadly
      enhanced activation of post-synaptic glutamate receptors (ionotropic and
      metabotropic) is proconvulsant. Antagonists of NMDA receptors and AMPA receptors
      are powerful anticonvulsants in many animal models of epilepsy. A clinical
      application of pure specific glutamate antagonists has not yet been established.
      Many different alterations in glutamate receptors or transporters can potentially
      contribute to epileptogenesis. Several genetic alterations have been shown to be
      epileptogenic in animal models but no specific mutation relating to glutamatergic
      function has yet been linked to a human epilepsy syndrome. There is clear
      evidence for altered NMDA receptor function in acquired epilepsy in animal models
      and in man. Changes in metabotropic receptor function may also play a key role in
      epileptogenesis.

PMID- 9932390
TI  - Effects of antiepileptic drugs on the activation of glutamate receptors.

PMID- 9932391
TI  - Antiepileptic drug treatment: clinical considerations and concerns.

PMID- 9932392
TI  - The glutamate synapse: a target in the pharmacological management of hyperalgesic
      pain states.

PMID- 9932393
TI  - The glutamate synapse in neuropsychiatric disorders. Focus on schizophrenia and
      Alzheimer's disease.
AB  - Here we have described a novel excitotoxic process in which hypofunctional NMDA
      receptors cease driving GABA ergic neurons which cease inhibiting excitatory
      transmitters in the brain. These disinhibited excitatory transmitters then act in
      concert to slowly hyperstimulate neurons in corticolimbic brain regions. We have
      discussed how such an abnormality could exist in the brains of individuals with
      schizophrenia or AD and could account for the clinical stigmata of the two
      disorders. In addition, we have highlighted how other disorder-specific factors
      would account for the differences in the clinical presentation of AD and
      schizophrenia. In an animal model, pharmacological methods have been developed
      for preventing the overstimulation of these vulnerable corticolimbic pyramidal
      neurons and at least some of these methods may be applicable for treating AD and
      schizophrenia.

PMID- 9932394
TI  - The glutamate synapse as a therapeutical target: perspectives for the future.

PMID- 9932395
TI  - Neuronal cell death: an updated view.

PMID- 9932396
TI  - Corticosteroid hormones and neuronal vulnerability: towards identification of
      candidate vulnerability genes.

PMID- 9932398
TI  - Studying signal transduction in neuronal cells: the Trk/NGF system.

PMID- 9932397
TI  - Ubiquitin and its role in neurodegeneration.

PMID- 9932399
TI  - Developmental changes in the neurotrophic factor survival requirements of
      peripheral nervous system neurons.

PMID- 9932400
TI  - Regulation of brain-derived neurotrophic factor mRNA levels in hippocampus by
      neuronal activity.
AB  - Neuronal activity increases synthesis of brain-derived neurotrophic factor (BDNF)
      mRNA in vivo and in vitro. We have investigated the pathways through which
      neuronal activity stimulated by kainic acid regulates BDNF mRNA levels in
      cultured hippocampal neurons and transgenic mice. Kainic acid induced the
      transcription of BDNF mRNA without influencing the mRNA stability. Interestingly,
      the half-life of the 4.2 kb BDNF transcript was much shorter than that of the 1.6
      kb transcript (23 +/- 4 min. vs. 132 +/- 30 min). Increase in the BDNF mRNA
      levels by kainic acid was not blocked by the protein synthesis inhibitor
      cycloheximide demonstrating that BDNF is regulated as an immediate early gene in
      hippocampal neurons. Although calmodulin antagonists are known to abolish the
      effect of kainic acid on BDNF mRNA, this effect was very similar in Ca(+2)
      calmodulin-dependent protein kinase II alpha knock-out mice and in wild-type
      mice. Surprisingly, even high doses of kainic acid failed to increase nerve
      growth factor (NGF) mRNA in mouse hippocampus although elevation in rat brain has
      been consistently observed.

PMID- 9932402
TI  - Neurotrophin receptors in Alzheimer's disease.

PMID- 9932401
TI  - Instructive roles of neurotrophins in synaptic plasticity.
AB  - Together, these experiments show that neurotrophins regulate neuronal function in
      a factor-dependent fashion, both in terms of membrane excitability and dendritic
      growth, and indicate that neurotrophins can play instructive roles in regulating
      neuronal phenotype and function. Given that neurons generally receive
      neurotrophic inputs from many different cellular sources, both regional and
      distant (e.g., via axonal and dendritic projections), instructive actions of
      neurotrophic factors may contribute to matching the morphology and electrical
      function of neurons to the neural circuits of which they are part. Moreover,
      during ongoing development and function of the nervous system, these same or
      similar neurotrophic factors may be key instructive signals in regulating
      synaptic plasticity of neural circuits.

PMID- 9932403
TI  - Discrete clusters of axonin-1 and NgCAM at neuronal contact sites: facts and
      speculations on the regulation of axonal fasciculation.

PMID- 9932404
TI  - Molecular mechanisms of commissural axon pathfinding.

PMID- 9932406
TI  - Semaphorin III: role in neuronal development and structural plasticity.

PMID- 9932405
TI  - Semaphorin-mediated neuronal growth cone guidance.

PMID- 9932407
TI  - Role for semaphorin III and its receptor neuropilin-1 in neuronal regeneration
      and scar formation?

PMID- 9932408
TI  - Eph receptors and ligands in axon pathway choice, target recognition, and
      synaptogenesis.

PMID- 9932410
TI  - Cellular activation in neuroregeneration.

PMID- 9932412
TI  - Oligodendrocyte regeneration in the adult rodent CNS and the failure of this
      process in multiple sclerosis.

PMID- 9932411
TI  - Cellular and molecular correlates of the regeneration of adult mammalian CNS
      axons into peripheral nerve grafts.
AB  - Studies of the regeneration of CNS axons into peripheral nerve grafts have
      provided information crucial to our understanding of the regenerative potential
      of CNS neurons. Injured axons in the thalamus and corpus striatum produce
      regenerative sprouts within a few days of graft implantation, apparently in
      response to living cells in the grafts. The regenerating axons often grow
      directly towards the grafts, and enter Schwann cell columns where they elongate
      surrounded by Schwann cell processes. The regenerating CNS axons, and the Schwann
      cell processes along which they grow, initially express the cell adhesion
      molecules NCAM, and L1. The axons also express polysialic acid and, unlike
      regenerating peripheral axons, bind tenascin-C derived from Schwann cells.
      Wherever peripheral nerve grafts are implanted into the CNS they appear to
      promote the differential regeneration of CNS axons. Most of the axons which grow
      into grafts in the thalamus are derived from the thalamic reticular nucleus
      (TRN), whereas grafts in the striatum promote regeneration of axons from the
      substantia nigra pars compacta (SNpc) and grafts in the cerebellum promote
      regeneration from deep cerebellar nuclei (DCN) and brainstem precerebellar
      neurons. In contrast most thalamocortical projection neurons, striatal projection
      neurons and Purkinje cells in the cerebellar cortex are poor at regenerating.
      There are patterns to the expression of regeneration-related molecules by axons
      injured by nerve grafts in the CNS. Most neurons which regenerate well (e.g. TRN
      and DCN neurons) upregulate GAP-43, L1 and the transcription factor c-jun in
      response to a graft, whereas those neurons which do not regenerate well (e.g.
      Purkinje cells, thalamocortical and striatal projection neurons) do not
      upregulate these molecules. These observations suggest that some classes of CNS
      neurons may be intrinsically unable to regenerate axons and the repair of
      injuries in the brain and spinal cord may consequently require some form of gene
      therapy for axotomised neurons.

PMID- 9932409
TI  - Boundary molecules during brain development, injury, and persistent neurogenesis-
      in vivo and in vitro studies.

PMID- 9932413
TI  - Genetic basis of peripheral neuropathies.

PMID- 9932414
TI  - Neuropathological hallmarks of Alzheimer's and Parkinson's diseases.

PMID- 9932415
TI  - Neurofibrillary pathology of Alzheimer's disease and other tauopathies.

PMID- 9932416
TI  - A new approach to the genetic analysis of nervous system diseases: retrospective
      genotyping of archival brains.

PMID- 9932417
TI  - Alzheimer's disease: identification of genes and genetic risk factors.

PMID- 9932419
TI  - Strain dependent and invariant features of transgenic mice expressing Alzheimer
      amyloid precursor proteins.

PMID- 9932418
TI  - Neurodegenerative Alzheimer-like pathology in PDAPP 717V-->F transgenic mice.
AB  - In summary, PDAPP mice overexpressing a mutation associated with some cases of
      familial early-onset AD express several of the major pathological hallmarks
      associated with AD. Amyloid plaques in PDAPP mice appear quite similar to A beta
      deposits in AD as shown by a variety of different antibodies and stains, and are
      of both the diffuse and compacted varieties. Additionally, a subset of these
      amyloid plaques appear to be neuritic plaques. Neurodegenerative changes,
      including the loss of synaptic and dendritic proteins, abnormal phosphorylation
      of cytoskeletal elements, subcellular degenerative changes, and the deposition of
      lysosomal and acute phase proteins has also been seen in PDAPP mouse brains.
      Reactive astrocytosis and microgliosis have also been observed in association
      with the amyloid plaques in the PDAPP mice. No neurofibrillary tangles or paired
      helical filaments have been found in the mice to date. It remains unknown whether
      mice are capable of generating these in a manner comparable to AD in less than
      two years. Extensive behavioral analyses are currently being performed in these
      mice, and preliminary results indicate that the PDAPP mice are significantly
      impaired on a variety of different learning and memory tests. In conclusion, the
      PDAPP mouse model doesn't display all the pathological hallmarks of AD, but it
      does display most of them in a robust manner that increases with age and gene
      dosage. Therefore, this transgenic model provides evidence that alterations in
      APP processing and A beta production can result in AD-like neuropathology, can
      contribute to a mechanistic understanding of AD (since examination of AD brains
      yields a static view, and we are unable to view the development of various
      pathological changes), as well as providing an useful animal model for the
      testing of various therapeutic interventions directed towards specific aspects of
      the neurodegenerative process.

PMID- 9932420
TI  - Reduced neuronal activity and reactivation in Alzheimer's disease.
AB  - 1. Alzheimer's disease is a multifactorial disease in which age and APOE-epsilon
      4 are important risk factors. Various mutations and even viral infections such as
      herpes simplex (Itzhaki et al., 1997) may play an additional role. 2. The
      neuropathological hallmarks of Alzheimer's disease (AD), i.e. amorphous plaques,
      neuritic plaques (NPs), pretangles, neurofibrillary tangles (NFT) and cell death
      are not part of a single pathogenetic cascade but are basically independent
      phenomena. 3. Pretangles can occur in neurons from which the metabolic rate is
      not altered. However, in brain areas where classical AD changes, i.e. NPs and
      NFTs, are present, such as the CA1 area of the hippocampus, the nucleus basalis
      of Meynert and the tuberomamillary nucleus, a decreased metabolic rate is found.
      Decreased metabolic rate appears to be an independent phenomenon in Alzheimer's
      disease. It is not induced by the presence of pretangles, NFT or NPs. 4.
      Decreased metabolic rate may precede cognitive impairment and is thus an early
      occurring hallmark of Alzheimer's disease, which, in principle, may be
      reversible. The observation that the administration of glucose or insulin
      enhances memory in Alzheimer patients also supports the view that Alzheimer's
      disease is basically a metabolic disease. Moreover, several observations indicate
      that activated neurons are better able to withstand aging and AD, a phenomenon
      paraphrased by us as "use it or lose it". It is, therefore, attractive to direct
      the development of therapeutic strategies towards restimulation of neuronal
      metabolic rate in order to improve cognition and other symptoms in Alzheimer's
      disease. A number of pharmacological and non-pharmacological studies support the
      concept that activation of the brain indeed has beneficial effects on several
      aspects of cognition and other central functions.

PMID- 9932421
TI  - Dinucleotide deletions in neuronal transcripts: a novel type of mutation in non
      familial Alzheimer's disease and Down syndrome patients.

PMID- 9932422
TI  - Pathogenesis of neurodegenerative diseases associated with expanded glutamine
      repeats: new answers, new questions.
AB  - Eight diseases are now known to be caused by an expansion mutation of the
      trinucleotide repeat CAG encoding glutamine. Each disease is caused by a CAG
      expansion in a different gene, and the genes bear no similarity to each other
      except for the presence of the repeat. Nonetheless, the essential feature of all
      of these disorders is neurodegeneration in a set of overlapping cortical and
      subcortical regions. Disease age of onset, and in some cases severity, is
      correlated with repeat length. These and other observations have led to the
      hypothesis that CAG expansion causes disease by a toxic gain-of-function of the
      encoded stretch of polyglutamine residues. Expansion-induced abnormalities of
      cytoskeletal function or neuronal signalling processes may contribute to the
      pathogenic process. In addition, theoretical and experimental analysis of the
      chemistry of uninterrupted stretches of glutamine residues suggest that
      polyglutamine-containing proteins or protein fragments may aggregate, via a
      "polar zipper", into beta pleated sheets. Recent findings have now established
      the presence of such aggregates in selected regions of brain from affected
      individuals, in transgenic mice expressing expanded repeats, and in isolated
      cells transfected with expanded repeats. The aggregates are most prominently
      manifest as neuronal intranuclear inclusion bodies. As the investigation of the
      link between these inclusions and cell dysfunction and death continues, it is
      possible that new avenues for therapeutic intervention will emerge.

PMID- 9932424
TI  - The small heat shock protein alpha B-crystallin as key autoantigen in multiple
      sclerosis.

PMID- 9932423
TI  - Molecular studies of prion diseases.

PMID- 9932425
TI  - Spinal cord injury: bridging the lesion and the role of neurotrophic factors in
      repair.

PMID- 9932426
TI  - Neurotrophin gene therapy in CNS models of trauma and degeneration.

PMID- 9932427
TI  - Gene therapy for inherited neurological disorders: towards therapeutic
      intervention in the Lesch-Nyhan syndrome.

PMID- 9932428
TI  - Towards gene therapy of neurodegenerative disease.

PMID- 9932429
TI  - Prospectives for cell and gene therapy in Huntington's disease.

PMID- 9932430
TI  - Regulation of neuronal nitric oxide synthase and identification of novel nitric
      oxide signaling pathways.
AB  - Neuronal nitric oxide synthase (nNOS) participate in a variety of physiologic and
      pathologic processes in the nervous system. nNOS was originally felt to be a
      constitutively expressed enzyme, but recent observations suggest that its levels
      are dynamically controlled in response to neuronal development, plasticity and
      injury. nNOS expression is regulated through alternative promoter usage through
      alternative mRNA splicing and it is likely that this plays an important role in
      the inducibility of gene expression in response to extracellular stimuli.
      Emerging data also suggests that NO may be the key mediator linking activity to
      gene expression and long-lasting neuronal responses through NO activating p21Ras
      through redox-sensitive modulation.

PMID- 9932431
TI  - Genetic analysis of NOS isoforms using nNOS and eNOS knockout animals.
AB  - All three major isoforms of nitric oxide synthase (NOS) are expressed in the
      brain. Because of complex and overlapping expression patterns (Marletta, 1994;
      Nathan and Xie, 1994), the particular NOS isoform involved in many processes is
      not clear. In fact, NO generated by separate isoforms may have different roles
      and potentially opposing effects (Iadecola et al., 1994). We have taken a genetic
      approach, to disrupt or knockout the genes for NOS isoforms to circumvent some of
      the limitations of pharmacologic agents. This approach allows the study of each
      individual NOS isoform in physiologic processes in the context of intact animals.
      It gives insights into possible developmental roles for NO and parallel processes
      that may compensate for the absence of each NOS isoform. We have made nNOS and
      eNOS knockout mice, as well as double knockout mice that lack both nNOS and eNOS
      isoforms (Huang et al., 1993; Huang et al., 1995; Son et al., 1996). In this
      chapter, we review some of the physiologic roles for NO that have been elucidated
      making use of these mice, including regulation of cerebral blood flow, response
      to cerebral ischemia, regulation of neurotransmitter release in the brain, and
      development of synaptic plasticity. Other chapters will discuss results using NOS
      knockout animals in studies of long term potentiation (see Hawkins, this volume),
      neuronal development (see Mize, this volume), and potential mechanisms for
      protection in nNOS knockout mice (Moskowitz, M.A.; Dawson, V.L, this volume).

PMID- 9932432
TI  - Monitoring neuronal NO release in vivo in cerebellum, thalamus and hippocampus.
AB  - A variety of methods has been developed based on in vivo microdialysis which
      allow one to examine the NO/cGMP signal transduction system in action in behaving
      animals. The extracellular levels of cGMP, the NO oxidative products nitrate and
      nitrite, and NO itself can all be determined. Using these methods changes in NO
      and cGMP production in response to pharmacological manipulations can be examined
      in vivo. In addition, it has been discovered that the activity of this system
      varies with the behavioral state of the animal. NO and cGMP appear to act via
      distinct downstream effectors in different brain regions. This opens up the
      possibility of selectively manipulating NO and cGMP signaling in discrete
      neuronal populations.

PMID- 9932433
TI  - A web-accessible digital atlas of the distribution of nitric oxide synthase in
      the mouse brain.
AB  - We have produced a digital atlas of the distribution of nitric oxide synthase
      (NOS) in the mouse brain as a reference source for our studies on the roles of
      nitric oxide in brain development and plasticity. NOS was labeled using
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry.
      In addition, choline acetyltransferase (ChAT) immunocytochemistry was used to
      identify cholinergic cells because many of the NADPHd positive cells were thought
      to colocalize acetylcholine. Some sections were also labeled with antibodies to
      either the neuronal (nNOS) or endothelial (eNOS) isoforms of NOS. Series of
      sections from 11 C57/BL6 mice were collected and labeled for NADPHd and/or ChAT.
      We collected two types of data from this material: color digital photographs
      illustrating the density of cell and fiber labeling, and computer/microscope
      plots of the locations of all the labeled cells in selected sections. The data
      can be viewed as either a series of single-section maps produced by combining the
      plots with the digital images, or as 3-D views derived from the cell plots. The
      atlas of labeled cell maps, together with selected color photographs and 3-D
      views, is available for viewing via the World Wide Web
      (http:@nadph.anatomy.lsumc.edu). Examination of the atlas data has revealed
      several points about the distribution of NOS throughout the mouse brain. Firstly,
      different populations of NADPHd-positive neurons can be distinguished by
      different patterns of staining. In some brain areas neurons are intensely stained
      by the NADPHd technique where label fills the cell bodies and much of the
      dendritic trees. In other brain regions labeling is much lighter, is principally
      confined to the cytoplasm of the cell soma, and extends only a short distance
      within proximal dendrites. Intense labeling is typical of neurons in the
      caudate/putamen and mesopontine tegmental nuclei. Most of the labeled neurons in
      the cortex also stain this way. Lighter, "granular" label is found in many other
      nuclei, including the medial septum, hippocampus, and cerebellum. In addition to
      staining pattern, we have also noted that different subpopulations of NOS-neurons
      can be distinguished on the basis of colocalization with ChAT. Substantial
      overlap of the distributions of these two substances was observed although very
      little colocalization was found in most cholinergic cell groups except the
      mesopontine tegmental nuclei. Other points of interest arising from this project
      include the apparent lack of NADPHd labeling in the CA1 pyramidal cells of the
      hippocampus or the Purkinje neurons in the cerebellum. This observation is
      especially relevant given that synaptic plasticity in these regions is reported
      to be nitric-oxide dependent.

PMID- 9932434
TI  - Why is the role of nitric oxide in NMDA receptor function and dysfunction so
      controversial?

PMID- 9932435
TI  - Redox modulation of the NMDA receptor by NO-related species.
AB  - The chemical reactions of NO are largely dictated by its redox state. Increasing
      evidence suggests that the various redox states of the NO group exist
      endogenously in biological tissues. In the case of NO+ equivalents, the mechanism
      of reaction often involves S-nitrosylation (transfer of the NO group to a
      cysteine sulfhydryl to form an RS-NO); further oxidation of critical thiols can
      possibly form disulfide bonds. We have physiological and chemical evidence that
      NMDA receptor activity can be modulated by S-nitrosylation, resulting in a
      decrease in channel opening. Recent data suggest that NO-, probably in the
      singlet (or high-energy) state, can also react with critical sulfhydryl group(s)
      of the NMDA receptor to down-regulate its activity; in the triplet (lower-energy)
      state NO- may oxidize these NMDA receptor sulfhydryl groups by formation of an
      intermediate such as peroxynitrite. It has also been reported that NO can react
      with thiol but only under specific circumstances, e.g., if an electron acceptor
      such as O2 is present, as well at catalytic amounts of metals like copper, and if
      the conditions do not favor the kinetically preferred reaction with O2.- to yield
      peroxynitrite. Mounting evidence in many fields suggests that S-nitrosylation can
      regulate the biological activity of a great variety of proteins, perhaps
      analogous to phosphorylation. Thus, this chemical reaction is gaining acceptance
      as a newly-recognized molecular switch to control protein function via reactive
      thiol groups such as those encountered on the NMDA receptor.

PMID- 9932436
TI  - The subcellular distribution of nitric oxide synthase relative to the NR1 subunit
      of NMDA receptors in the cerebral cortex.
AB  - Results from several electrophysiological studies predict that the neuronal NO
      synthesizing enzyme, nNOS, resides within spines formed by pyramid-to-pyramid axo
      spinous synaptic junctions of the cortex. On the other hand, light microscopic
      neuroanatomical detection of nNOS within pyramidal neurons has been difficult,
      suggesting that these neurons contain nNOS at levels below threshold for
      detection. Our results obtained by electron microscopic immunocytochemistry
      indicate that nNOS occurs within spiny neurons, such as those of pyramidal
      neurons, albeit discretely within their spines. Dual electron microscopic
      immunocytochemistry, whereby antigenic sites to the NR1 subunit of NMDA receptors
      are probed simultaneously with sites immunoreactive for nNOS, reveals that some,
      although not all, nNOS within spines co-exist with NR1 subunits. Additionally,
      immunoreactivity for the NR1 subunit is detectable within nNOS-axons, indicating
      that NO may be generated in response to axo-axonic interactions with
      glutamatergic axons in the vicinity and independently of action potential
      propagation. Immunoreactivity for NR1 subunits within axons (with or without nNOS
      immunoreactivity) may additionally serve to confer receptivity of these axons to
      NO generated coincidentally with activity. Analysis of the visual cortex of
      monocular adult animals indicates that the level of nNOS within neurites is
      dependent on chronic activity levels of the surrounding neuropil and independent
      of somatic input level. Together, these findings point to plasticity of nNOS
      neurons within adult brain tissue, involving regulation of subcellular nNOS
      distribution.

PMID- 9932437
TI  - Nitric oxide as a signaling molecule in visual system development.
AB  - The lateral geniculate nucleus (LGN) of the ferret is characterized by the
      readily discernible anatomical patterning of afferent terminations from the
      retina into both eye-specific layers and On/Off sublaminae. The eye-specific
      layers form during the first post-natal week, and On/Off sublaminae become
      apparent during the third to fourth post-natal weeks. The post-natal appearance
      of these patterns thus provides an advantageous model for the study of the
      mechanisms of activity-dependent development. The second phase of pattern
      formation, the appearance of On/Off sublaminae, involves the elaboration of
      appropriately placed axonal terminals and the restriction (or retraction) of
      inappropriately placed terminals. Previous work has demonstrated that this
      process is dependent on the activation of NMDA-receptors. Other studies have
      provided strong evidence that nitric oxide, a diffusible gas which is produced
      downstream of NMDA-receptor activation, acts as a retrograde messenger molecule
      to induce changes in pre-synaptic structures. In this article we review the
      evidence that nitric oxide plays a role in activity-dependent synaptic plasticity
      in the developing retinogeniculate pathway. The role of nitric oxide in other
      aspects of visual system development is also discussed.

PMID- 9932438
TI  - Mechanisms involved in development of retinotectal connections: roles of Eph
      receptor tyrosine kinases, NMDA receptors and nitric oxide.
AB  - Axons of retinal ganglion cells exhibit a specific pattern of connections with
      the brain. Within each visual nucleus in the brain, retinal connections are
      topographic such that axons from neighboring ganglion cells have neighboring
      synapses. Research is beginning to shed light on the mechanisms responsible for
      development of topographic connections in the visual system. Much of this
      research is focused on the axonal connections of the retina with the tectum. In
      vivo and in vitro experiments indicate that the pattern of retinotectal
      connections develops in part due to positional labels carried by the growing
      retinal axons and by the tectal cells. Evidence suggests that gradients of Eph
      receptor tyrosine kinases serve as positional labels on the growing retinal
      axons, and gradients of ligands for these receptors serve as positional labels in
      the tectum. Blocking expression of EphA3, a receptor tyrosine kinase, in the
      developing retina resulted in disruption of the topography of the retinotectal
      connections, further supporting the role of these, molecules. Although positional
      labels appear to be important, other mechanisms must also be involved. The
      initial pattern of retinotectal connections lacks the precision seen in the
      adult. The adult pattern of connections arises during development by activity
      dependent refinement of a roughly ordered prepattern. The refinement process
      results in elimination of projections to the wrong side of the brain, to non
      visual nuclei and to inappropriate regions within a nucleus. Blocking NMDA
      receptors during the period of refinement preserved anomalous retinotectal
      projections, which suggests that elimination of these projections is mediated by
      NMDA receptors. Furthermore, tectal cells normally express high levels of nitric
      oxide synthase (NOS) during the period of refinement, and blocking nitric oxide
      (NO) synthesis also preserved inappropriate projections. Thus, both NMDA
      receptors and NO appear to be involved in refinement. Blocking NMDA receptor
      activation reduced NOS activity in tectal cells, which suggests the possibility
      that NO is the downstream mediator of NMDA function related to refinement. A
      quantitative comparison of blocking NMDA receptors, NO synthesis or both showed
      that all three treatments have comparable effects on refinement. This indicates
      that the role of NMDA receptor activation relative to refinement may be
      completely mediated through nitric oxide. Quantitative analysis also suggests
      that other mechanisms not involving NMDA receptors or NO must be involved in
      refinement. Other mechanisms appear to include cell death.

PMID- 9932439
TI  - The role of nitric oxide in development of the patch-cluster system and
      retinocollicular pathways in the rodent superior colliculus.
AB  - Nitric oxide (NO) has been implicated as a retrograde signal in the process of
      refining axonal pathways during brain development. To determine some of the
      factors involved in this process, we have used two model pathway systems in the
      rat and mouse superior colliculus (SC). The first, the patch-cluster system,
      consists of clusters of neurons in the intermediate gray layer (igl) which
      transiently express NO during development and which receive input from a
      cholinergic pathway from the parabrachial brainstem as well as from other
      pathways containing different transmitters. The second system, the
      retinocollicular pathway, consists of glutamatergic fibers that project to the
      superficial gray layer. We have used both nitric oxide synthase inhibition (nw
      nitro-L-arginine, NoArg) and single (nNOS) and double (nNOS and eNOS) gene
      knockout mice to examine the effect that reduction in NOS has upon the
      development of these two systems. The onset of NOS expression in rat, as revealed
      by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeling,
      occurred in igl cells as early as postnatal day P5, with clusters being well
      established by P14. Cholinergic fibers were first visible at P10 and formed
      obvious patches and tiers by P14. Intraperitoneal injections of NoArg from P1-P22
      had no effect upon the development of these cholinergic patches. The pathway also
      developed normally in both single and double-knockout mice. In contrast, the
      ipsilateral retinocollicular pathway was altered in the double, but not in the
      single knockout mouse. This pathway is exuberant during the first week of life,
      being distributed across much of the mediolateral axis of the rostral SC. By P8
      P15, this pathway has retracted to the most mediorostral SC. This refinement was
      delayed substantially in the double NOS gene knockout mouse. Ipsilateral fibers
      were found within 3-5 separate medio-lateral patches within the rostral 600
      microns of SC at P15, and patches of abnormal size and extent were also seen at
      P18. We conclude from these results that NO plays a role in pathway development
      in the rodent SC, but only in glutamatergic pathways and only when both
      endothelial and neuronal forms of NOS have been deleted. The mechanism of this
      effect must involve pathway elimination in situations where there is non
      correlated electrical activity. It is likely that NO promotes fiber retraction
      rather than fiber stabilization in these developing nerve fibers.

PMID- 9932440
TI  - Nitric oxide as a retrograde messenger during long-term potentiation in
      hippocampus.
AB  - Nitric oxide (NO) is widespread in the nervous system and is thought to play a
      role in a variety of different neuronal functions, including learning and memory
      (see other chapters, this volume). A number of behavioral studies have indicated
      that NO is involved in several types of learning such as motor learning
      (Yanagihara and Kondo, 1996), avoidance learning (Barati and Kopf, 1996;
      Myslivecek et al., 1996), olfactory learning (Okere et. al., 1996; Kendrick et
      al., 1997), and spatial learning (Holscher et al., 1995; Yamada et al., 1996)
      (for review of earlier papers see Hawkins, 1996). Moreover, NO is thought to be
      involved in neuronal plasticity contributing to these different types of learning
      in different brain areas including the cerebellum (chapter by R. Tsien, this
      volume) and hippocampus. In this chapter we review evidence on the role of NO in
      long-term potentiation (LTP), a type of synaptic plasticity in hippocampus that
      is believed to contribute to declarative forms of learning such as spatial
      learning.

PMID- 9932441
TI  - Modulation of LTP induction by NMDA receptor activation and nitric oxide release.
AB  - In the CA1 hippocampal region, the induction of long-term potentiation (LTP)
      requires activation of N-methyl-D-aspartate receptors (NMDARs). However, untimely
      NMDAR activation either immediately prior to or following tetanic stimulation
      inhibits LTP generation. This NMDAR-mediated LTP inhibition is overcome by
      inhibitors of nitric oxide synthase (NOS) and hemoglobin, suggesting the
      involvement of NO. Additionally, NO inhibitors can promote the ability of weak
      tetanic stimuli to produce LTP under basal conditions in hippocampal slices.
      Recent experiments indicate that untimely NMDAR activation contributes to the
      failure of LTP induction during periods of low glucose exposure and hypoxia.
      Following hypoxia there is also a delayed form of LTP inhibition that is reversed
      by NMDAR antagonists and NO inhibitors. These results suggest that there are
      physiological and pathological conditions during which NMDAR activation and NO
      release modulate the induction of synaptic plasticity.

PMID- 9932442
TI  - Dynamic modulation of cerebral cortex synaptic function by nitric oxide.
AB  - Our experiments demonstrate that NO exerts several actions in the cerebral cortex
      (see Fig. 4). Its production is mediated by neuronal activity through at least
      two pathways, NMDA receptors and AMPA receptors. By virtue of its diffusion in
      extracellular space, NO can interact with synapses that are near the production
      site but not necessarily anatomically connected to the NO source by a
      conventional synaptic linkage. NO's primary action is amplification of the
      release of the excitatory neurotransmitter, L-glutamate, thus effectively
      creating a positive feed-forward gain system. However, a number of effective
      brakes, presumably activated under physiological conditions, serve to limit the
      cascade. These include NO's ability to inhibit NMDA receptors, its negative
      feedback on the rate limiting enzyme, NOS (Rengasamy and Johns, 1993; Park et
      al., 1994; Ravichandran et al., 1995) and other inhibitory actions (Figs. 3H and
      L). Under conditions of extremely strong activation or curtailment of the
      inhibitory feedback mechanisms, as might occur with a change in the local redox
      milieu (see Lipton, this volume), the amplification cascade may proceed unchecked
      leading to neurotoxicity (see Dawson, this volume). NO's ability to modulate
      synaptic function is indicated by both its positive and negative modulatory role
      in a form of activity-dependent synaptic plasticity, covariance-induced synaptic
      potentiation. These opposing effects may be due to NO's ability to amplify
      glutamate release and inhibit NMDA receptors, respectively. The actions of
      endogenous NO in vivo are primarily facilitatory in visual cortex (Fig. 4).
      However, inhibitory actions also occur in vivo. The targets for NO in vivo, are
      potentially more diverse including the neurotransmitter release process, NMDA
      receptors, other receptors and ion channels and the cerebral vasculature.
      However, regardless of the signaling pathways, the net result of endogenous NO
      production in the intact visual cortex is a potent modulation of cells' responses
      to visual stimulation. Thus, it is likely that this signal plays an important
      role in ongoing information processing in the mature cerebral cortex, dynamically
      altering the effective strength of cortical networks.

PMID- 9932443
TI  - Interaction of nitric oxide and external calcium fluctuations: a possible
      substrate for rapid information retrieval.

PMID- 9932444
TI  - Nitric oxide in neurodegeneration.
AB  - Nitric oxide (NO) is a unique biological messenger molecule which mediates
      diverse physiologic roles. NO mediates blood vessel relaxation by endothelium,
      immune activity of macrophages and neurotransmission of central and peripheral
      neurons. NO is produced from three NO Synthase (NOS) isoforms: Neuronal NOS
      (nNOS), endothelial NOS, and inducible NOS (iNOS). In the central nervous system,
      NO may play important roles in neurotransmitter release, neurotransmitter
      reuptake, neurodevelopment, synaptic plasticity, and regulation of gene
      expression. However, excessive production of NO following a pathologic insult can
      lead to neurotoxicity. NO plays a role in mediating neurotoxicity associated with
      a variety of neurologic disorders, including stroke, Parkinson's Disease, and HIV
      dementia.

PMID- 9932445
TI  - Mechanisms of NO neurotoxicity.

PMID- 9932446
TI  - Glial glutamate transport as target for nitric oxide: consequences for
      neurotoxicity.
AB  - Overwhelming evidence suggest that accumulations of extracellular glutamate are
      toxic to neurons. It has also been proposed that astrocytes protect neurons from
      glutamate toxicity by removal of glutamate from extracellular space. By using co
      cultures of hippocampal neurons and astrocytes, we studied the influence of
      astrocytes on neuronal excitotoxicity. Moreover, we evaluated the role of nitric
      oxide and pro-inflammatory cytokines on astrocytic glutamate transport.

PMID- 9932447
TI  - Expression of nitric oxide synthase-2 in glia associated with CNS pathology.

PMID- 9932448
TI  - Role of endogenous nitric oxide and peroxynitrite formation in the survival and
      death of motor neurons in culture.
AB  - Motor neuron survival is highly dependent on trophic factor supply. Deprivation
      of trophic factors results in induction of neuronal NOS, which is also found in
      pathological conditions. Growing evidence suggests that motor neuron degeneration
      involves peroxynitrite formation. Trophic factors modulate peroxynitrite toxicity
      (Estevez et al., 1995; Shin et al., 1996; Spear et al., 1997). Whether a trophic
      factor prevents or potentiates peroxynitrite toxicity depends upon when the cells
      are exposed to the trophic factor (Table 1). These results strongly suggest that
      a trophic factor that can protect neurons under optimal conditions, but under
      stressful conditions can increase cell death. In this context, it is possible
      that trophic factors or cytokines produced as a response to damage may potentiate
      rather than prevent motor neuron death. A similar argument may apply to the
      therapeutic administration of trophic factors to treat neurodegenerative
      diseases. Similarly, the contrasting actions of NO on motor neurons may have
      important consequences for the potential use of nitric oxide synthase inhibitors
      in the treatment of ALS and other related neurodegenerative diseases.

PMID- 9932450
TI  - Structural and functional characteristics of Dyrk, a novel subfamily of protein
      kinases with dual specificity.
AB  - Dyrk-related kinases represent a novel subfamily of protein kinases with unique
      structural and enzymatic features. Its members have been identified in distantly
      related organisms. The yeast kinase, Yak1, has been characterized as a negative
      regulator of growth. Mnb from Drosophila is encoded by the minibrain gene, whose
      mutation results in specific defects in neurogenesis. Its mammalian homolog,
      Dyrk1A, is activated by tyrosine phosphorylation in the activation loop between
      subdomains VII and VIII of the catalytic domain. The human gene for Dyrk1A is
      located in the "Down syndrome critical region" of chromosome 21 and is therefore
      a candidate gene for mental retardation in Down syndrome. More recently, six
      additional mammalian Dyrk-related kinases have been identified (Dyrk1B, Dyrk1C,
      Dyrk2, Dyrk3, Dyrk4A, and Dyrk4B). All members of the Dyrk family contain in the
      activation loop the tyrosines that are essential for the full activity of Dyrk1A.
      Outside their catalytic domains, Dyrk kinases exhibit little sequence similarity
      except for a small segment immediately preceding the catalytic domain (DH-box,
      Dyrk homology box). An unusual enzymatic property of Dyrk-related kinases is
      their ability to catalyze tyrosine-directed autophosphorylation as well as
      phosphorylation of serine/threonine residues in exogenous substrates. The exact
      cellular function of the Dyrk kinases is yet unknown. However, it appears
      reasonable to assume that they are involved in the regulation of cellular growth
      and/or development.

PMID- 9932449
TI  - The neuromessenger platelet-activating factor in plasticity and
      neurodegeneration.
AB  - Synaptic activation leads to the formation of arachidonic acid, platelet
      activating factor (PAF, 1-O-alkyl-2-acyl-sn-3-phosphocholine) and other lipid
      messengers. PAF is a potent bioactive phospholipid in synaptic plasticity. PAF
      enhances presynaptic glutamate release, is a retrograde messenger in long-term
      potentiation and enhances memory formation. PAF also couples synaptic events with
      gene expression by stimulating a FOS/JUN/AP-1 transcriptional signaling system,
      as well as transcription of COX-2 (inducible prostaglandin synthase). Since the
      COX-2 gene is also involved in synaptic plasticity, the PAF-COX-2 pathway may
      have physiological significance. Seizures, ischemia and other forms of brain
      injury promote phospholipase A2 (PLA2) overactivation, resulting in the
      accumulation of bioactive lipids at the synapse. PAF, under these pathological
      conditions, behaves as a neuronal injury messenger by at least two mechanisms:
      (a) enhancing glutamate release; and, (b) by sustained augmentation of COX-2
      transcription. These events link PAF with neurodegeneration. The upstream
      intracellular pathways of signal transduction involved in neuronal or
      photoreceptor cell apoptosis are not well understood and involve stress sensitive
      kinases. PAF is a transcriptional activator of the COX-2 gene. BN 50730, a potent
      intracellular PAF antagonist, blocks COX-2 induction. COX-2 transcription and
      protein expression are upregulated in the hippocampus in kainic acid induced
      epileptogenesis. There is a selectively elevated induction of COX-2 (72-fold) by
      kainic acid preceding neuronal cell death. BN 50730 administered by i.c.v.
      injection blocks seizure-induced COX-2 induction. Overall, PAF is a dual
      modulator of neural function and becomes an endogenous neurotoxin when over
      produced.

PMID- 9932451
TI  - Transcriptional and posttranscriptional regulation of proteoglycan gene
      expression.
AB  - Proteoglycans are among the most complex and sophisticated molecules of mammalian
      systems in terms of their protein and carbohydrate moieties. These macromolecules
      are in a continuous interplay with each other and the cell surface signal
      transducing pathways, some of which are beginning to be elucidated. Because of
      their domain structure, catalytic potential, and diversity, these molecules
      appear to be designed for integrating numerous signaling events. For example,
      some proteoglycans interact with hyaluronan and lectins, thereby linking cell
      surfaces and distant matrix molecules. Some interact with collagen during the
      complex process of fibrillogenesis and regulate this biological process
      fundamental to animal life. Others interact with growth factors and serve as
      depot available during growth or tissue remodeling. In this review, we center on
      the most recent developments of proteoglycan biology, focusing primarily on
      genomic organization and transcriptional and posttranscriptional control. We
      discuss only those proteoglycans whose gene and promoter elements have been
      characterized and proved to be functional. When possible, we correlate the
      effects of growth factors and cytokines on proteoglycan gene expression with the
      topology of cis-acting elements in their genomic control regions. The analysis
      leads to a comprehensive critical appraisal of the principles that underlie the
      regulation of proteoglycan gene expression and to the delineation of common
      regulatory mechanisms.

PMID- 9932452
TI  - Degradation of mRNA in Escherichia coli: an old problem with some new twists.
AB  - Metabolic instability is a hallmark property of mRNAs in most if not all
      organisms and plays an essential role in facilitating rapid responses to
      regulatory cues. This article provides a critical examination of recent progress
      in the enzymology of mRNA decay in Escherichia coli, focusing on six major
      enzymes: RNase III, RNase E, polynucleotide phosphorylase, RNase II, poly(A)
      polymerase(s), and RNA helicase(s). The first major advance in our thinking about
      mechanisms of RNA decay has been catalyzed by the possibility that mRNA decay is
      orchestrated by a multicomponent mRNA-protein complex (the "degradosome"). The
      ramifications of this discovery are discussed and developed into mRNA decay
      models that integrate the properties of the ribonucleases and their associated
      proteins, the role of RNA structure in determining the susceptibility of an RNA
      to decay, and some of the known kinetic features of mRNA decay. These models
      propose that mRNA decay is a vectorial process initiated primarily at or near the
      5' terminus of susceptible mRNAs and propagated by successive endonucleolytic
      cleavages catalyzed by RNase E in the degradosome. It seems likely that the
      degradosome can be tethered to its substrate, either physically or kinetically
      through a preference for monphosphorylated RNAs, accounting for the usual "all or
      none" nature of mRNA decay. A second recent advance in our thinking about mRNA
      decay is the rediscovery of polyadenylated mRNA in bacteria. Models are provided
      to account for the role of polyadenylation in facilitating the 3' exonucleolytic
      degradation of structured RNAs. Finally, we have reviewed the documented
      properties of several well-studied paradigms for mRNA decay in E. coli. We
      interpret the published data in light of our models and the properties of the
      degradosome. It seems likely that the study of mRNA decay is about to enter a
      phase in which research will focus on the structural basis for recognition of
      cleavage sites, on catalytic mechanisms, and on regulation of mRNA decay.

PMID- 9932453
TI  - Regulation of mammalian ribosomal gene transcription by RNA polymerase I.
AB  - All cells, from prokaryotes to vertebrates, synthesize vast amounts of ribosomal
      RNA to produce the several million new ribosomes per generation that are required
      to maintain the protein synthetic capacity of the daughter cells. Ribosomal gene
      (rDNA) transcription is governed by RNA polymerase I (Pol I) assisted by a
      dedicated set of transcription factors that mediate the specificity of
      transcription and are the targets of the pleiotrophic pathways the cell uses to
      adapt rRNA synthesis to cell growth. In the past few years we have begun to
      understand the specific functions of individual factors involved in rDNA
      transcription and to elucidate on a molecular level how transcriptional
      regulation is achieved. This article reviews our present knowledge of the
      molecular mechanism of rDNA transcriptional regulation.

PMID- 9932454
TI  - The initiation of DNA base excision repair of dipyrimidine photoproducts.
AB  - One of the major DNA repair pathways is base excision repair, in which DNA bases
      that have been damaged by endogenous or exogenous agents are removed by the
      action of a class of enzymes known as DNA glycosylases. One subset of the known
      DNA glycosylases has an associated abasic lyase activity that generates a
      phosphodiester bond scission. The base excision pathway is completed by the
      sequential action of abasic endonucleases, DNA polymerases, and DNA ligases. Base
      excision repair of ultraviolet (UV) light-induced dipyrimidine photoproducts has
      been described in a variety of prokaryotic and eukaryotic organisms and phages.
      These enzymes vary significantly in their exact substrate specificity and in the
      catalytic mechanism by which repair is initiated. The prototype enzyme within
      this class of UV-specific DNA glycosylases is T4 endonuclease V. Endonuclease V
      holds the distinction of being the first glycosylase (1) to have its structure
      solved by X-ray diffraction of the enzyme alone as well as in complex with
      pyrimidine dimer-containing DNA, (2) to have its key catalytic active site
      residues identified, and (3) to have its mechanism of target DNA site location
      determined and the biological relevance of this process established. Thus, the
      study of endonuclease V has been critical in gaining a better understanding of
      the mechanisms of all DNA glycosylases.

PMID- 9932455
TI  - Domain organization, genomic structure, evolution, and regulation of expression
      of the aggrecan gene family.
AB  - Proteoglycans are complex macromolecules, consisting of a polypeptide backbone to
      which are covalently attached one or more glycosaminoglycan chains. Molecular
      cloning has allowed identification of the genes encoding the core proteins of
      various proteoglycans, leading to a better understanding of the diversity of
      proteoglycan structure and function, as well as to the evolution of a
      classification of proteoglycans on the basis of emerging gene families that
      encode the different core proteins. One such family includes several
      proteoglycans that have been grouped with aggrecan, the large aggregating
      chondroitin sulfate proteoglycan of cartilage, based on a high number of sequence
      similarities within the N- and C-terminal domains. Thus far these proteoglycans
      include versican, neurocan, and brevican. It is now apparent that these proteins,
      as a group, are truly a gene family with shared structural motifs on the protein
      and nucleotide (mRNA) levels, and with nearly identical genomic organizations.
      Clearly a common ancestral origin is indicated for the members of the aggrecan
      family of proteoglycans. However, differing patterns of amplification and
      divergence have also occurred within certain exons across species and family
      members, leading to the class-characteristic protein motifs in the central
      carbohydrate-rich region exclusively. Thus the overall domain organization
      strongly suggests that sequence conservation in the terminal globular domains
      underlies common functions, whereas differences in the central portions of the
      genes account for functional specialization among the members of this gene
      family.

PMID- 9932456
TI  - Modulation of DNA damage and DNA repair in chromatin.
AB  - DNA is packaged in the highly compact and dynamic structure of chromatin in
      eukaryotic cells. It is generally accepted that DNA processing events in the
      nucleus, such as transcription, replication, recombination, and repair, are
      restricted by this packaging. For some processes (e.g., transcription), the
      chromatin fiber is "preset" in a more open structure to allow access of proteins
      to specific regions of DNA within this structural hierarchy. These regions
      contain modified nucleosomes that accommodate a less compact state of chromatin
      and allow access to specific regions of DNA. DNA repair proteins, however, must
      access DNA lesions in all structural domains of chromatin after sudden insult to
      the genome. Damaged DNA must be recognized, removed, and replaced by repair
      enzymes at all levels of chromatin packaging. Therefore, the modulation of DNA
      damage and its repair in chromatin is crucial to our understanding of the fate of
      potential mutagenic and carcinogenic lesions in DNA. In this review, we discuss
      the modulation of DNA damage and DNA repair by chromatin structure, and the
      modulation of chromatin structure by these events.

PMID- 9932458
TI  - Regulation of RNA polymerase I transcription in yeast and vertebrates.
AB  - This article focuses on what is currently known about the regulation of
      transcription by RNA polymerase I (pol I) in eukaryotic organisms at opposite
      ends of the evolutionary spectrum--a yeast, Saccharomyces cerevisiae, and
      vertebrates, including mice, frogs, and man. Contemporary studies that have
      defined the DNA sequence elements are described, as well as the majority of the
      basal transcription factors essential for pol I transcription. Situations in
      which pol I transcription is known to be regulated are reviewed and possible
      regulatory mechanisms are critically discussed. Some aspects of basal pol I
      transcription machinery appear to have been conserved from fungi to vertebrates,
      but other aspects have evolved, perhaps to meet the needs of a metazoan organism.
      Different parts of the pol I transcription machinery are regulatory targets
      depending on different physiological stimuli. This suggests that multiple
      signaling pathways may also be involved. The involvement of ribosomal genes and
      their transcripts in events such as mitosis, cancer, and aging is discussed.

PMID- 9932457
TI  - The search for trans-acting factors controlling messenger RNA decay.
AB  - Control of mRNA turnover is an integral component of regulated gene expression.
      Individual mRNAs display a wide range of stabilities, which in many cases have
      been linked to discrete sequence elements. The most extensively characterized
      determinants of rapid constitutive mRNA turnover in mammalian systems are A + U
      rich elements (AREs), first identified in the 3' untranslated regions of many
      cytokine/lymphokine and protooncogene mRNAs. In this article, we describe recent
      advances in the characterization of ARE-directed mRNA turnover, including links
      to deadenylation kinetics and functional heterogeneity among AREs from different
      mRNAs. We then describe strategies employed in the search for trans-acting
      factors interacting with these elements. Using such techniques, an ARE-binding
      activity capable of accelerating c-myc mRNA turnover in vitro was identified, and
      named AUF1. Subsequent cloning and characterization revealed that AUF1 exists as
      a family of four proteins formed by alternative splicing of a common pre-mRNA and
      appears to function as part of a multisubunit trans-acting complex to promote ARE
      directed mRNA turnover. Investigations using several systems have demonstrated
      that AUF1 expression and/or activity correlate with rapid decay of ARE-containing
      mRNAs, and that both expression and activity of AUF1 are regulated by
      developmental and signal transduction mechanisms.

PMID- 9932459
TI  - Regulation of the Bacillus subtilis pyrimidine biosynthetic operon by
      transcriptional attenuation: control of gene expression by an mRNA-binding
      protein.
AB  - The pyrimidine nucleotide biosynthetic (pyr) operon of Bacillus subtilis is
      regulated by a transcriptional attenuation mechanism in which termination of
      transcription at points upstream of the genes being regulated is promoted by the
      binding of a regulatory protein, PyrR, to specific sequences in the pyr mRNA.
      Binding of PyrR to pyr mRNA is stimulated by uridine nucleotides and causes
      changes in the mRNA secondary structure. This model is supported by extensive
      molecular genetic analysis. PyrR, which is encoded by the first gene of the pyr
      operon, is also a uracil phosphoribosyltransferase, although it has little amino
      acid sequence resemblance to other bacterial uracil phosphoribosyltransferases.
      Purified B. subtilis pyrR promotes attenuation of pyr transcription in vitro and
      binds specifically to pyr RNA sequences. The crystallographic structure of PyrR
      demonstrates the similarity of its tertiary structure to other
      phosphoribosyltransferases and suggests the surface to which RNA binds. PyrR is
      widely distributed among eubacteria and appears to regulate pyr genes not only by
      the attenuation mechanism found in B. subtilis, but also by a coupled
      transcription-translation attenuation mechanism and by acting as a translational
      repressor. PyrR illustrates the concept that transcriptional attenuation is a
      much more widespread and mechanistically versatile mechanism for the regulation
      of gene expression in bacteria than is generally recognized.

PMID- 9932460
TI  - DNA damage and replication checkpoints in the fission yeast, Schizosaccharomyces
      pombe.
AB  - Eukaryotic organisms have developed an array of mechanisms for minimizing the
      consequences of damage to their DNA molecules and the consequences of
      interference with their DNA replication. Among these mechanisms are the DNA
      damage and replication checkpoints, which inhibit passage from one cell cycle
      stage to the next when DNA is damaged or replication is incomplete. Studies of
      these checkpoints in the fission yeast, Schizosaccharomyces pombe, complement
      studies in other organisms and provide valuable insight into the nature of the
      proteins responsible for these checkpoints and how such proteins may function.

PMID- 9932461
TI  - Modern radiotherapy and local control in oncology.

PMID- 9932462
TI  - Points of view. With reference to: RAYS 23, 1 1998 Tuberculosis.

PMID- 9932463
TI  - Treatment planning in radiation oncology and impact on outcome of therapy.
AB  - Irradiation is effective treatment for many patients with cancer. It can
      completely eradicate the tumor in the irradiated volume or it provides palliative
      relief to patients with incurable cancer. The success of radiation therapy
      depends on the delivery of an adequate dose to the entire tumor volume with
      acceptable morbidity in the surrounding normal tissues. The goals are to achieve
      the highest probability of local and regional tumor control with the lowest
      achievable incidence of side effects and to prolong the life of the patient with
      the best possible quality of life. Although treatment planning is extremely
      helpful in determining the best form of therapy, the responsibility for critical
      judgment and execution rests with the radiation oncologist, who, to treat
      patients effectively, must have sufficient training to define the target volume
      and critical structures, to interpret treatment planning information and to guide
      the physicist or dosimetrist in achieving the best dose distribution; have
      sufficient knowledge to select the best possible combination of dose and
      fractionation for a given site and volume; be competent to judge the quality of
      the dose distribution and the technical feasibility and accuracy of proposed
      plan; and understand the capabilities and limitations of the staff and computer
      systems involved in the radiation treatment planning process. No computer
      software can correct the radiation oncologist's errors of clinical judgment,
      misunderstanding of physical concepts, or inadequate treatment delivery.

PMID- 9932464
TI  - Brachytherapy and local control.
AB  - Locoregional control of primary tumor is fundamental to cure since only in one
      third of patients the onset of distant metastases is the major cause of
      therapeutic failure. Thus recently, all therapeutic approaches aimed at the
      enhancement of locoregional control have been considered with growing interest.
      More particularly, brachytherapy alone or in combined modality therapy as an
      important option in the local treatment of various malignant tumors, has been
      widely used; this being related to the now available information on dose-rate,
      remote after-loading procedures, the new, safe and handy radionuclides and
      computerized dosimetry systems which allow a more accurate and rapid dose
      calculation. These advances have led to a wider application of brachytherapy.
      Together with the classical indications for head and neck and cervical tumors,
      brachytherapy plays now a well-established role in the treatment of breast,
      brain, gastrointestinal, genitourinary, soft tissue lung and eye tumors.

PMID- 9932465
TI  - Intraoperative radiotherapy. Literature updating with an overview of results
      presented at the 6th International Symposium of Intraoperative Radiation Therapy.
AB  - Intraoperative radiotherapy is a technique that can be integrated into
      multidisciplinary treatment strategies in oncology. A radiation boost delivered
      with high energy electron beams can intensify locoregional antitumor therapy in
      patients undergoing cancer surgery. Intraoperative radiotherapy can increase the
      therapeutic index of the conventional combination of surgery and radiotherapy by
      improving the precision of radiation dose location, while decreasing the normal
      tissue damage in mobile structures and enhancing the biological effect of
      radiation when combined with surgical debulking. Intraoperative radiotherapy has
      been extensively investigated in clinical oncology in the last 15 years.
      Commercially available linear accelerators require minimal changes to be suitable
      for intraoperative radiotherapy. Its successful implementation in clinical
      protocols depends on the support given by the single institutions and on a
      clinical research-oriented mentality. Tumors where intraoperative radiotherapy as
      a treatment component has shown promising rates of local control include locally
      advanced rectal, gastric and gynecologic cancer, bone and soft tissue sarcoma.
      Intraoperative radiotherapy can be applied to brain tumors, head and neck cancer,
      NSCLC and pancreatic carcinoma.

PMID- 9932466
TI  - Stereotactic radiosurgery with linear accelerator.
AB  - Stereotactic radiosurgery is a method that applies a radiation dose to a limited
      and well-defined volume while the irradiation of adjacent healthy tissues is
      minimized. It is most commonly used in the treatment of intracranial lesions
      because the skull hardness assures the stable location of its contents. Treatment
      of the rest of the body has recently been proposed and carried out, using
      original immobilization systems. Stereotactic radiosurgery was first described in
      1951 by the Swedish neurosurgeon Lars Leksell who originally used X-rays and then
      high-energy protons as a source of radiation. In the '80s photons from linear
      accelerators were used as radiation source, with various stereotactic systems and
      computerized treatment planning. The method used with all radiosurgical systems,
      regardless of the source of irradiation, is similar. The lesion is detected with
      common diagnostic imaging and adequate location frames. At present, to prevent
      errors in location, MRI and CT data are matched using an Image Fusion computer
      program. The objective of stereotactic radiosurgery is to destroy tumor cells or
      to induce changes in tissues that, as in brain arteriovenous malformations lead
      to the occlusion of their abnormal vessels. Stereotactic radiosurgery is
      increasingly used today in the treatment of a variety of intracranial lesions to
      the patients' benefit.

PMID- 9932467
TI  - Conformal radiation therapy with hadron beams and the programs of the TERA
      Foundation.
AB  - Proposed fifty years ago, tumor therapy with charged hadron beams has been under
      rapid development since 1993-94. Indeed hadrontherapy was born in 1938, when
      neutron beams have been used in cancer therapy, but it has become an accepted
      therapeutical modality only in the last five years. Fast neutrons are still in
      use, even if their limitations are now apparent. Charged hadron beams are more
      favorable, since the largest specific energy deposition occurs at the end of
      their range in matter. The most used hadrons are at present protons and carbon
      ions. Both allow a dose deposition which conforms to the tumor target.
      Radiobiology experiments and the results of the first clinical trials indicate
      that carbon ions have, on top of this macroscopic property, a different way of
      interacting with cells at the microscopic level. There are thus solid hopes to
      use carbon beams of about 4500 MeV to control tumors which are radioresistant
      both to X-rays and protons. After discussing these macroscopic and microscopic
      properties of hadrontherapy, the twelve dedicated hadrontherapy centres, which
      will be treating patients from 2001-2002, are shortly described. Five of them are
      in the USA and seven in Japan, while no hospital based centre for deep
      protontherapy is fully financed in Europe. The second part of this review is
      devoted to the Italian hadrontherapy programme, based on the development of the
      network RITA, the construction in Rome by the "Istituto Superiore di Sanita" of a
      novel proton accelerator based on a 3 GHz linac, the design of a linac to boost
      the energy of protons extracted from a 50-70 MeV cyclotron and the construction
      in Mirasole, near Milano, of a center for protons and ions known as "CNAO". This
      center will have a synchrotron, which is under design at CERN in the framework of
      a collaboration of TERA with AUSTRON and GSI which is called PIMMS (Proton Ion
      Medical Machine Study) and is headed by Dr. Phyl Bryant.

PMID- 9932468
TI  - Chemoradiation followed by surgery: its role in local control in advanced
      cervical cancer.
AB  - The aim of this study was to improve local control and consequently survival, by
      using chemoradiation followed by surgery. After a median follow-up of 57+ months,
      95% CI (9-111) five year overall survival (OS) was 81.8%, 90% and 85.7% in stage
      Ib2-IIa bulky, IIb and III-IVa, respectively (p = NS). Disease-free survival
      (DFS) was 81.8% 80% and 71.4% (p = NS) and disease-free survival of local failure
      (DFSLF) was 95.4%, 80% and 100% (p = NS) for stage Ib2-IIa, bulky, IIb and III
      IVa respectively. Distant metastases were present in every group, ranging from
      13.6% to 17% in the early bulky and advanced groups respectively. Pathologic
      findings revealed complete response (CR) (no residual disease or scattered
      microscopic tumoral foci) in 27/40 (67%), and partial response (PR) in 11/40
      (27%). According to the pathologic response, DFS was 92.6% and 50% (p = 0.0029)
      and DFSLF was 100% and 77.8% (p = 0.0127) in complete and partial response
      respectively. This therapeutical approach promoted a high rate of pathologic
      complete response (PCR) PCR as well as of local control in this group at high
      risk for recurrence.

PMID- 9932469
TI  - Local control assessment in clinical oncology.
AB  - The true significance of achieving local control has been a matter for debate
      among clinical oncologists for many years and still is for those tumors where
      distant metastases are the major cause of failure and mortality. The assessment
      of local control appears elusive as it may be conceived as the local eradication
      of neoplastic cells while this should be confirmed by no risk for recurrence.
      Tools and procedures are available to assess separately the local response after
      treatment and at long term. Direct methods are quite different according to the
      different clinical and pathologic conditions. Complete local responses may be
      followed by recurrence leading to a different approach: to wait for the
      appearance of recurrence rather than to pursue a complete response. The
      diagnostic clinical and instrumental methods while easy in superficial tumors,
      are complex, expensive and poorly reliable in deep-seated tumors. Thus, in
      general, any assessment of local control in terms of diagnostic work-up can
      frequently be difficult and misleading.

PMID- 9932471
TI  - Radiation, hormonotherapy, survival and local control in prostatic carcinoma.
AB  - The combination of concomitant external beam radiotherapy (ERT) and neoadjuvant
      hormonotherapy was shown to be able to significantly improve local control and
      disease-free survival in locally advanced prostatic carcinoma. (RTOG study 8610).
      Aim of this analysis was to assess the clinical results observed in a population
      of patients undergoing this combined treatment and, more particularly, to examine
      the prognostic impact of local control. 84 patients (T2: 47%, T3: 49.4%, T4:
      3.6%) underwent concomitant ERT (dose to pelvic volume: 45 Gy; mean dose to
      prostatic volume: 65 Gy) and neoadjuvant hormonotherapy (flutamide: 250 mg three
      times/daily for 30 days; LH-RH analogue: 1 oral dose every 28 days starting 2
      months prior to radiotherapy and for its whole duration). With a median follow-up
      of 36 months, 3.6% of patients were deceased; hematogenous metastases and local
      disease progression were recorded in 16.7% and 4.8% of patients, respectively.
      Local disease progression was shown to be significantly correlated with the
      incidence of metastases. In fact, the actuarial incidence of metastases at 5
      years was 100% and 27% in patients with and without local recurrence (p = 0.0043)
      respectively. Overall, metastases-free local and biochemical recurrence-free
      survival was 89.2%, 66.5%, 85.0% and 41.9% respectively. At univariate analysis
      (logrank) the clinical stage (T) was shown to be significantly correlated with
      the incidence of metastases (p = .0004) and local progression (p < .0001). In
      conclusion, this study has confirmed the low rate of local progression with the
      combination of hormonotherapy and radiotherapy and the significant correlation of
      local control with the incidence of hematogenous metastases.

PMID- 9932470
TI  - Radiotherapy, local control and survival in carcinomas of the exocrine pancreas.
AB  - Local recurrence affects approximately 50% of patients undergoing surgery for
      pancreatic adenocarcinoma. To lower the incidence of locoregional recurrence, the
      combination with surgery of adjuvant radiotherapy has been proposed. The latter
      is based on external radiotherapy (ERT), intraoperative radiotherapy (IORT) or
      their combination. To evaluate the impact on local control and survival, results
      achieved in a a group of patients undergoing surgical resection and combined
      adjuvant radiotherapy, are analyzed. 17 patients with adenocarcinoma of the
      exocrine pancreas were treated with a therapeutic protocol based on
      pancreatectomy and intraoperative radiotherapy (IORT) to the tumor bed (10 Gy)
      followed by postoperative radiotherapy (50 Gy); 9 patients underwent also
      preoperative radiotherapy (5 Gy) to the pancreas and liver. With a median follow
      up of 45 months, in 3 patients (17.6%) local recurrence was observed while 12
      patients (70.6%) showed liver metastases or peritoneal spread. Median survival
      was 17.5 months and actuarial survival at 2 and 5 years was 41.2% and 11.2%,
      respectively. As compared to a moderate local control, the prognosis of patients
      undergoing surgical resection remained disappointing. Thus, the effort of
      improving results with new therapeutic modalities as preoperative
      radiochemotherapy and adjuvant chemotherapy, seems justified.

PMID- 9932472
TI  - Radiotherapy, local control and survival in brain tumors.
AB  - High grade glial brain tumors and brain metastases are a complex subject with
      still unsatisfactory therapeutic results for the frequent absence of early and
      precise diagnosis as well as for the limited therapeutic interval between the
      tumor and presumed healthy tissues. The therapeutic problems of cellular hypoxia,
      the rapid recovery of sublethal damage for neoplastic cells, the rapid regrowth,
      have led to a number of efforts to deliver the dose of radiotherapy in various
      associations. The constant technological trend to increase the high dose gradient
      to the peripheral tumor, is reported.

PMID- 9932473
TI  - Chemoradiotherapy with carboplatin in continuous infusion in the locoregional
      control of advanced head and neck cancer.
AB  - Because of the difficulty to achieve and maintain locoregional control in head
      and neck cancer, many clinical trials were focused on the addition of
      chemotherapy to locoregional treatments in advanced head and neck cancer
      patients. In particular, concomitant chemoradiotherapy resulted in high response
      rate and improved local control, sometimes with increased toxicity. In the effort
      to improve local control a phase II study on chemoradiotherapy with carboplatin
      in prolonged continuous infusion for 14 days (420 mg/m2 total dose) during
      standard radiotherapy, was performed. 45 patients were evaluable for response: CR
      62.5% (global response 96%). After a mean follow-up of 48 months 9/28 patients
      with CR were still alive with no evidence of disease; two additional patients
      were alive but with locoregional disease. As for deceased patients, one died from
      non-tumor related causes, 13 from locoregional disease and 2 for metastatic
      disease. If the entire population of Crs is analyzed, it is observed that 13
      patients (46.5% of CRs and 29% of the entire series) maintained a durable
      locoregional control. In most patients recurrence was detectable both in the
      primary tumor and in the neck.

PMID- 9932474
TI  - Local control in breast cancer: impact on survival.
AB  - The role of radiotherapy in breast cancer is examined, based on a review of
      literature. Its impact on survival is discussed in the framework of a
      multidisciplinary treatment of the disease.

PMID- 9932475
TI  - Radiotherapy, local control and survival in cervical carcinoma.
AB  - The natural history of cervical carcinoma is characterized by a close correlation
      between local control and survival. Local eradication of the disease is justified
      for the obvious impact on the quality of life as well as on long-term survival. A
      series of analyses carried out in the last decades have elucidated the role of a
      number of prognostic factors in local control. Among treatment modalities applied
      to attain this aim, particular interest has been focused in recent years on
      concomitant radiation and chemotherapy. While some experiences have shown
      promising results, the precise role of this combination will be defined based on
      the outcomes of some randomized studies now in progress. Among the modalities of
      concomitant radiation and chemotherapy, some authors have proposed the following
      sequence: neoadjuvant chemotherapy and surgical resection. It is an aggressive
      approach potentially associated to major side-effects. This therapeutic modality
      will require an accurate assessment of clinical results both in terms of clinical
      response, local control and effects on organ function and quality of life.

PMID- 9932476
TI  - Radiotherapy, local control and survival in lung cancer.
AB  - Better local control in locally advanced IIIA-B non small cell lung cancer, not
      considered for surgery, can be achieved through therapy intensification with non
      conventional fractionation of radiation dose, concomitant boost to the tumor
      volume, conformal therapy and combined modality therapy. All these procedures
      tend to produce an improved response, which, if stable in time, may also improve
      local control and survival. The reported experiences define a positive and
      encouraging trend on which new guidelines for a more suitable definition of
      standard therapies for the disease can be modulated.

PMID- 9932477
TI  - Radiotherapy and local control in rectal cancer.
AB  - Recurrence is a stage in the natural history of rectal cancer. Preoperative
      radiotherapy or postoperative radiochemotherapy lower the rate of recurrence,
      improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of
      the "Universita Cattolica del S. Cuore" of Rome 380 patients with rectal cancer
      of early clinical stage T2-3, candidates for surgery for cure, underwent
      radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy);
      45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after
      surgery), of whom 7 were treated with preoperative radiotherapy alone; 145
      patients underwent preoperative concomitant radiochemotherapy according to 3
      different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU;
      radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy)
      combined with 5-FU and folinic acid. 71 patients were treated with preoperative
      radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years.
      Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The
      rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for
      "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for
      preoperative radiotherapy combined with IORT. Local control was shown to be
      significantly better with preoperative treatment as compared to postoperative
      treatment (p = 0.02). The incidence of metastases was 35% in the patients with
      local recurrence and 16% in those with local control. The difference in survival
      was highly significant in patients with local control as compared to those with
      local recurrence: at 5 years 87% and 32% respectively. Patients with local
      control showed a lower incidence of metastasis and a better survival.

PMID- 9932479
TI  - Mechanisms of regulation and functions of guanylyl cyclases.

PMID- 9932478
TI  - Cancer of the anal canal and local control.
AB  - Concomitant radiochemotherapy is the standard treatment of squamous cell
      carcinoma of the anal canal. It can afford a high local control rate though the
      same impact has not been observed on survival. A few reports have concerned the
      impact of local control on distant metastases and survival. From 1988 to 1998 at
      the "Divisione di Radioterapia" of the "Universita Cattolica del S. Cuore" of
      Rome 30 patients with squamous cell carcinoma of the anal canal were treated for
      cure. Treatment consisted of two cycles of radiotherapy (23.4 Gy) with a 4-5 week
      split in each cycle. 5FU (100 mg/sqm/24 h) was administered in continuous
      infusion for the first 4 days of therapy; mitomycin C (10 mg/sqm bolus) was
      administered on day 1, 4-6 weeks after the end of cycle 2 of concomitant
      radiochemotherapy, patients received a boost of interstitial brachytherapy. Local
      control on T of all patients was 84% at 5 years. Six patients showed locoregional
      recurrence: 3 recurrences on T and 4 disease progressions in locoregional lymph
      nodes. 3 of 6 patients underwent salvage surgery. The initial extent of the
      disease, the patient's age and brachytherapy boost did not have a statistically
      significant influence on local control. Two of the 30 patients showed liver
      metastases, and at their appearance, one patient was free of local disease while
      the other showed locoregional progression after Miles' operation for salvage. The
      metastasis-free interval was not significantly influenced by local control,
      although at 5 years, 96% of patients with local control of T were free of
      metastases vs 75% of those with recurrence on T (p = 0.22). Overall actuarial
      survival at 5 years was 75%. The behavior of survival in our experience seemed to
      be significantly influenced by local control: in the group with local control, 5
      year survival was 85% vs 40% of patients with local recurrence (p = 0.01).

PMID- 9932480
TI  - Soluble guanylyl cyclase: structure and regulation.

PMID- 9932481
TI  - Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases
      (PDEs).

PMID- 9932482
TI  - Structure and function of cGMP-dependent protein kinases.

PMID- 9932483
TI  - Structure and function of cyclic nucleotide-gated channels.

PMID- 9932484
TI  - Signal transduction by cGMP-dependent protein kinases and their emerging roles in
      the regulation of cell adhesion and gene expression.

PMID- 9932485
TI  - Immunomodulation by colony-stimulating factors.

PMID- 9932486
TI  - Hyperpolarization-activated cation channels: a multi-gene family.

PMID- 9932487
TI  - Regulation of beta-adrenergic receptor responsiveness modulation of receptor gene
      expression.

PMID- 9932488
TI  - Fish intermediate filament proteins in structure, evolution, and function.

PMID- 9932489
TI  - Intermediate filament organization during oogenesis and early development in the
      clawed frog, Xenopus laevis.

PMID- 9932490
TI  - The complexity of gene families involved in epithelial differentiation. Keratin
      genes and the epidermal differentiation complex.

PMID- 9932491
TI  - Keratin modifications and solubility properties in epithelial cells and in vitro.
AB  - The gains that have been made in characterizing some of the keratin
      posttranslational modifications have helped answer some questions regarding these
      modifications and have generated an information base for asking additional
      refined questions in future studies. Highlights of where we believe we currently
      stand with regard to keratin posttranslational modifications are as follows: 1.
      Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been
      conclusively identified in K13, K8, and K18. Three serine glycosylation sites in
      the head domain of K18 have been identified, and it is possible that all keratins
      are glycosylated. The function of this modification remains to be defined, but is
      likely to be different from phosphorylation, since the two modifications are
      generally segregated on different molecules and several examples exist whereby
      both modifications increase simultaneously. 2. Keratin phosphorylation occurs
      within the tail and/or head domains of all keratins that have been examined.
      Several serine phosphorylation sites and some of the relevant kinases have been
      characterized in K8, K6, and K18, and serine/threonine sites have been identified
      in K1. Functions of keratin phosphorylation that have significant experimental
      support include a role in filament solubility and reorganization and a role in
      regulating keratin binding with other cytoplasmic proteins. The significance of
      filament reorganization and increased solubility under a variety of physiologic
      conditions such as mitosis and cell stress are important areas of future and
      ongoing investigation. Other associations with keratin phosphorylation include
      protection against cell stress, cell signaling, apoptosis, and cell compartment
      specific roles. At this stage, however, it is not known if these associations
      play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal
      and simple epithelial keratins under physiologic and pathologic states,
      respectively. In the physiological context, the role of this modification is
      clear in terms of providing a compact protective structure, while in the
      pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of
      K18 and K19 by caspases occurs during apoptosis, and generates stable keratin
      fragments that are highly enriched within the cytoskeletal compartment.
      Proteolysis of the type II keratins appears to be spared for reasons that remain
      to be defined. It is likely that this apoptosis-associated degradation involves
      all type I keratins. Keratin fragments are also noted in sera of patients in
      association with a variety of epithelial tumors. If a signal does exist for the
      apoptosis-associated fragmentation, aside from caspase activation, then it
      appears that the overall increase in keratin phosphorylation during apoptosis
      does not account for this signal. 5. Keratins undergo several other
      posttranslational modifications including disulfide bond formation (not found in
      K8/18 due to lack of cystienes) and acetylation of their N-terminal serines.
      Modification by lipids is also possible, but this modification requires further
      confirmation. 6. Keratin solublility is highly dynamic and varies profoundly
      depending on the keratin pair and the physiologic state of the cell. Within the
      keratin family, simple epithelial keratins are among the most soluble
      (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays
      an important role in modulating keratin solubility, and distinct differences
      occur in site-specific phosphorylation depending on the soluble versus
      cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18)
      also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

PMID- 9932492
TI  - Lessons from keratin transgenic and knockout mice.

PMID- 9932493
TI  - The wound repair-associated keratins 6, 16, and 17. Insights into the role of
      intermediate filaments in specifying keratinocyte cytoarchitecture.

PMID- 9932494
TI  - Cytokeratins as markers of differentiation in the diagnosis of epithelial tumors.

PMID- 9932495
TI  - Molecular dissection of desmosomal assembly and intermediate filament anchorage.

PMID- 9932496
TI  - Lens intermediate filament proteins.

PMID- 9932497
TI  - Structure, assembly, and dynamics of intermediate filaments.

PMID- 9932498
TI  - Measuring the assembly kinetics and binding properties of intermediate filament
      proteins.

PMID- 9932499
TI  - Viscoelasticity of intermediate filament networks.

PMID- 9932500
TI  - Transient electric birefringence in the study of intermediate filament assembly.

PMID- 9932501
TI  - Possible regulation of intermediate filament proteins by Rho-binding kinases.

PMID- 9932502
TI  - Vimentin and lipid metabolism.
AB  - Vimentin IFs form close associations with the lipid droplets that are
      characteristic of adipose and steroidogenic cells. There is good evidence that
      changes in vimentin expression or organization can alter the metabolism of
      specific lipid components in cultured preadipose and adrenal cell lines. However,
      the effect of vimentin on triglyceride stability that is observed in preadipose
      cells is not obviously reflected in adrenal cells or fibroblasts. Conversely, an
      effect of vimentin on the metabolism of lipoprotein-derived cholesterol observed
      in adrenal cells is not apparent in preadipose cells. While the complexity of the
      phenotypes observed in these cells might be associated with cell-type-specific
      differences in the metabolism of triglycerides or lipoprotein-derived
      cholesterol, these studies have not yet revealed a general role of vimentin in
      lipid metabolism that would indicate a common mechanism in all cell types. A key
      issue that needs to be addressed is whether the effect of vimentin IFs on the
      stability of triglycerides or the trafficking of GSLs and lysosomal cholesterol
      is due to a direct participation of vimentin IFs in some aspect of these
      processes, or perhaps reflects an indirect response of the lipid metabolism of
      these cells to an effect of vimentin on some other cellular process.

PMID- 9932504
TI  - The complexity of intermediate filaments in the nervous system.

PMID- 9932503
TI  - Desmin cytoskeleton in muscle integrity and function.

PMID- 9932505
TI  - Extensive phosphorylation and axonal transport of triton-soluble neurofilament
      subunits.
AB  - The low abundance of soluble neurofilament (NF) subunits in mature axons has
      suggested that newly synthesized NF proteins rapidly assemble into highly stable
      polymers and associate with the Triton X-100-insoluble cytoskeleton. Here we
      present evidence for multiple populations of NFs and NF subunits, distinguished
      by differential solubility in Triton, within perikarya and axons of neurons in
      situ and in culture. We further demonstrate, using microinjection of "tagged" NF
      subunits and by pulse-chase radiolabeling of endogenous NF subunits, that these
      soluble NF populations represent precursors for incorporation into the axonal
      cytoskeleton.

PMID- 9932506
TI  - Lamin assembly in vivo.

PMID- 9932507
TI  - Nuclear lamin-binding proteins.

PMID- 9932508
TI  - Control of retinoid nuclear receptor function and expression.

PMID- 9932509
TI  - Retinoid endocrinology from metabolism to cellular signaling.

PMID- 9932510
TI  - Structure and function of retinoid-binding proteins.

PMID- 9932511
TI  - The role of retinoids in developmental mechanisms in embryos.

PMID- 9932512
TI  - Antioxidant activity of vitamin A within lipid environments.

PMID- 9932513
TI  - Plasma vitamins A and E in HIV-positive patients.

PMID- 9932515
TI  - The role of carotenoids in modulating DNA stability and lipid peroxidation.
      Importance for human health.

PMID- 9932514
TI  - The bioconversion of beta-carotene into retinoids.

PMID- 9932516
TI  - beta-Carotene. An antioxidant or a target of oxidative stress in cells?

PMID- 9932517
TI  - Biophysical properties of carotenoids.

PMID- 9932518
TI  - The role of vitamin D3 and antiestrogens in modulating apoptosis of breast cancer
      cells and tumors.

PMID- 9932519
TI  - Vitamin D and intracellular calcium.

PMID- 9932520
TI  - Antioxidant chemistry of alpha-tocopherol in biological systems. Roles of redox
      cycles and metabolism.

PMID- 9932521
TI  - Localization of vitamin E in membranes.

PMID- 9932522
TI  - The molecular action of alpha-tocopherol in lipoprotein lipid peroxidation. Pro-
      and antioxidant activity of vitamin E in complex heterogeneous lipid emulsions.

PMID- 9932523
TI  - Vitamin E. Its role in aging.

PMID- 9932524
TI  - The role of linoleic acid in endothelial cell gene expression. Relationship to
      atherosclerosis.
AB  - There is evidence that linoleic acid plays a critical role in gene expression and
      vascular function as it relates to the pathogenesis of atherosclerosis. The lipid
      environment, particularly linoleic acid and its derivatives, of the vascular
      endothelium may profoundly influence the inflammatory response mediated by
      cytokines. Modulations in the level of activity of a select set of endothelial
      transcription factors appear to provide a mechanism for linking lipid/cytokine
      mediated vessel wall dysfunction, including endothelial cell activation, altered
      proteoglycan metabolism, and endothelial barrier dysfunction, with the onset of
      atherosclerotic lesion formation. The activity of endothelial transcription
      factors is in part regulated by the balance of cellular oxidative stress and
      antioxidant status. Our data suggest that linoleic acid can activate the vascular
      endothelium and may thus be an atherogenic fatty acid. Furthermore,
      nutrients/chemicals with antioxidant properties can protect endothelial cells
      against lipid-mediated cell injury, suggesting that oxidative stress is a
      critical component in linoleic acid-mediated gene expression. Our discoveries
      that linoleic acid can influence significantly the cytokine-mediated inflammatory
      response may open new fields in dietary intervention of atherosclerosis.

PMID- 9932525
TI  - Lipidic signaling and peroxisomal function.

PMID- 9932526
TI  - Vitamin K metabolism.

PMID- 9932527
TI  - Role of coenzyme Q and superoxide in vitamin E cycling.

PMID- 9932528
TI  - Prooxidant functions of coenzyme Q.

PMID- 9932529
TI  - BME recognizes pain control as good medicine. Tennessee Board of Medical
      Examiners.

PMID- 9932530
TI  - It keeps happening!

PMID- 9932531
TI  - Petit mal seizure in a child with Marfan's syndrome.
AB  - We report a case of a 17-year-old white girl with Marfan's syndrome and
      generalized absence-type seizures since 11 years of age. A video EEG recording
      for six hours demonstrated 52 episodes of clinical generalized absence-type
      seizures and three-per-second spike and wave epileptiform discharges,
      characteristic of petit mal epilepsy. Sodium valproate therapy was successful in
      controlling her seizures. In this article, we review various possible causes of
      epilepsy in patients with Marfan's syndrome.

PMID- 9932532
TI  - Multiple system atrophy: clinical presentation and diagnosis.
AB  - Multiple system atrophy (MSA) describes a relatively uncommon, debilitating
      disorder that is frequently misdiagnosed as Parkinson's disease. Patients with
      MSA show various combinations of parkinsonism, cerebellar ataxia, pyramidal signs
      and progressive autonomic failure, especially cardiovascular and urologic
      autonomic dysfunction. Few treatment options exist. Although some patients
      initially respond well to dopaminergic treatment for their parkinsonian symptoms,
      striatal degeneration occurs, and levodopa often becomes ineffective. Thus,
      physicians may provide only symptomatic treatment and support for patients with
      MSA. In this paper, we present a case study of a 68-year-old woman who came to
      the Vanderbilt Movement Disorders Clinic with severe autonomic dysfunction and
      parkinsonism, previously diagnosed as Parkinson's disease. Following autonomic
      function tests as well as clinical evaluation, she was diagnosed with MSA and
      began treatment for orthostatic hypotension and micturition dysfunction.

PMID- 9932533
TI  - Positive seat belt sign in three siblings involved in a single motor vehicle
      collision: the use of diagnostic laparoscopy.

PMID- 9932534
TI  - Physician reporting of communicable diseases in east Tennessee: implications for
      statewide underreporting.

PMID- 9932535
TI  - Oral ulcerations in a patient with sarcoidosis.

PMID- 9932536
TI  - Professional courtesy.

PMID- 9932538
TI  - Treating irritable bowel syndrome.

PMID- 9932537
TI  - Pain after shingles.

PMID- 9932539
TI  - A disease of too much iron.

PMID- 9932540
TI  - Wait or operate for abdominal aneurysms?...

PMID- 9932541
TI  - . . . a similar dilemma with brain aneurysms.

PMID- 9932542
TI  - More lactose in your life?

PMID- 9932543
TI  - Heart attack warning signs: beyond chest pain.

PMID- 9932544
TI  - Friends may be good for your heart.

PMID- 9932546
TI  - Echinacea questionable for colds.

PMID- 9932545
TI  - Antacid use can mask serious disease.

PMID- 9932547
TI  - Biofeedback, exercise for urge incontinence.

PMID- 9932548
TI  - Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6
      years.
AB  - OBJECTIVE: To assess 6 years' neurologic outcome of a complete cohort of
      survivors of intrauterine intravascular transfusions. METHODS: From January 1986
      to December 1991, 136 intravascular transfusions were performed in 43 fetuses
      presenting with signs of severe erythroblastosis. Before the initial transfusion,
      11 of 43 fetuses had some degree of hydrops fetalis, and hemoglobin values ranged
      between 1.5 and 10.7 g/dL. Neurologic outcome of a complete cohort of 35 long
      time survivors was assessed for up to 6 years by reviewing the hospital charts
      and questionnaires sent to the family physicians or pediatricians. RESULTS: Long
      time follow-up was available in all survivors with hydrops at initial transfusion
      (seven of seven) and in 23 of 28 survivors without hydrops. Only one of 35
      survivors had mild psychomotoric disabilities up to 1 year of age, but was free
      of sensorineural problems on further examination. In a second case, delayed
      speech development was observed. Fetuses presenting with hydrops fetalis before
      initial transfusion tended to have a higher perinatal mortality and had a
      significantly higher rate of preterm delivery (P = .03). However, moderate or
      severe neurologic impairment was never observed, even when severe cases with
      hydrops fetalis or extremely low hemoglobin levels were included. CONCLUSION:
      Treatment of severe fetal erythroblastosis by intrauterine intravascular
      transfusions is associated with a favorable neurologic long-time outcome.

PMID- 9932549
TI  - Maternal antiplatelet antibodies in predicting risk of neonatal thrombocytopenia.
AB  - OBJECTIVE: To determine the incidence of maternal antiplatelet antibodies in
      cases of thrombocytopenia during pregnancy, using the monoclonal antibody
      specific immobilization of platelet antigens assay; and to assess the usefulness
      of this assay for predicting risk of neonatal thrombocytopenia. METHODS: A total
      of 6770 pregnant women were included in the study, and the monoclonal antibody
      specific immobilization of platelet antigens assay was done when platelet counts
      were less than 150 x 10(9)/L. Platelet counts were determined in 6103 newborns.
      RESULTS: The incidence of maternal thrombocytopenia was 11.6% (95% confidence
      interval [CI] 10.8, 12.4). Among newborns, 1.3% (95% CI 0.5, 2.7) born to
      thrombocytopenic mothers were thrombocytopenic, compared with 0.4% (95% CI 0.2,
      0.6) born to nonthrombocytopenic women. Antiplatelet antibodies were detected in
      37 (8.6%) of 430 thrombocytopenic women; autoantibodies were detected in 28 cases
      (circulating or bound to platelets), alloantibodies in eight cases, and an
      association of alloantibodies and autoantibodies in one case. The positive and
      negative likelihood ratios for predicting neonatal thrombocytopenia were 4.6 and
      0.7, respectively. CONCLUSION: The monoclonal antibody-specific immobilization of
      platelet antigens assay did not predict the risk of neonatal thrombocytopenia in
      an unselected population of thrombocytopenic pregnant women.

PMID- 9932550
TI  - Effectiveness of antenatal steroids in obstetric subgroups.
AB  - OBJECTIVE: To determine the effectiveness of antenatal steroids in the reduction
      of neonatal morbidity and mortality in obstetric subgroups of preterm labor with
      intact membranes, preterm premature rupture of membranes (PROM), and pregnancy
      associated hypertension. The secondary objective was to determine the effect of
      antenatal steroids in appropriate for gestational age (AGA) and growth-restricted
      neonates. METHODS: We studied the neonatal outcomes for all women who delivered
      infants weighing 1750 g or less at birth between January 1990 and July 1997 at
      our institution. The study population was divided primarily into three clinical
      groups: preterm labor with intact membranes, PROM, and pregnancy-associated
      hypertension. Secondarily, the total population was divided based on birth weight
      and gestational age into AGA and growth-restricted neonates. Within each
      obstetric subgroup, neonates exposed to antenatal steroids were compared with
      unexposed neonates for respiratory distress syndrome (RDS), intraventricular
      hemorrhage and periventricular leukomalacia, the incidence of major brain
      lesions, necrotizing enterocolitis, proved neonatal sepsis, patent ductus
      arteriosus, and neonatal death. The subgroups were also compared for gestational
      age at delivery, birth weight, birth weight percentile, Apgar scores, postnatal
      surfactant exposure, and clinical and histologic chorioamnionitis. Descriptive
      statistics, Student t test, chi2, Fisher exact test, and logistic regression were
      used for analysis. RESULTS: A total of 1148 neonates weighing 1750 g or less were
      delivered during the study period. There were 447 and 410 neonates delivered
      after preterm labor with intact membranes and PROM, respectively, and 245
      neonates born to mothers with pregnancy-associated hypertension. Nine hundred
      twenty-eight neonates were AGA and the remaining 220 neonates were growth
      restricted. Antenatal steroids significantly decreased the incidence of RDS, the
      incidence and severity of intraventricular hemorrhage and periventricular
      leukomalacia, necrotizing enterocolitis, and neonatal mortality in preterm labor
      with intact membranes. In the presence of PROM, it significantly decreased the
      incidence and severity of intraventricular hemorrhage and periventricular
      leukomalacia and decreased neonatal mortality, with no apparent effect on the
      incidence of RDS. Antenatal steroids did not show any beneficial effect in
      pregnancy-associated hypertension and fetal growth restriction (FGR).
      Additionally, a significant increase was observed in the incidence of proved
      neonatal sepsis when antenatal steroids were used in pregnancy-associated
      hypertension. CONCLUSION: The effectiveness of antenatal steroids varies with the
      obstetric population studied. Antenatal steroids significantly decreased the
      incidence of major neonatal morbidity and mortality in the AGA preterm neonate
      delivered after preterm labor with intact membranes. Antenatal steroids did not
      show any benefit in cases of pregnancy associated with maternal hypertension or
      FGR. Its effect in the presence of PROM is limited to a significant reduction in
      the incidence and severity of intraventricular hemorrhage and periventricular
      leukomalacia and in neonatal death.

PMID- 9932551
TI  - Increased platelet-activating factor-acetylhydrolase activity in the umbilical
      venous plasma of growth-restricted fetuses.
AB  - OBJECTIVE: To determine whether platelet-activating factor-acetylhydrolase
      activity in fetal plasma obtained at birth from umbilical vessels is different
      from that in maternal plasma, and (2) to compare platelet-activating factor
      acetylhydrolase activity in cord plasma from fetuses with fetal growth
      restriction (FGR) and those with appropriate growth for gestational age (AGA).
      METHODS: Platelet-activating factor-acetylhydrolase activity was measured in the
      plasma of 22 nonpregnant healthy women, 16 pregnant women at term during labor,
      28 fetuses exhibiting AGA, and seven fetuses with FGR. RESULTS: Plasma platelet
      activating factor-acetylhydrolase activity in normotensive pregnant women at 37
      41 weeks' gestation was 28.1+/-16.6 nmol/mL per minute, which was not
      statistically different from the activity in nonpregnant women (30.8+/-11.1
      nmol/mL per minute). Platelet-activating factor-acetylhydrolase activity in
      venous cord plasma from AGA fetuses was significantly (P < .01) lower than that
      in maternal plasma (6.3+/-2.6 nmol/mL per minute), and there was no difference
      between the activities found in arterial and venous cord samples. In FGR fetuses,
      venous cord platelet-activating factor-acetylhydrolase activity was significantly
      (P < .01) higher (12.1+/-1.4 nmol/mL per minute), than the activity seen in AGA
      fetuses, and when the data from AGA and FGR fetuses were considered together,
      there was a negative correlation between cord plasma platelet-activating factor
      acetylhydrolase activity and neonatal body weight (r = .46, P = .006).
      CONCLUSION: Platelet-activating factor hydrolysis is significantly lower in
      fetuses than adults. Further, the comparatively high platelet-activating factor
      acetylhydrolase activity in FGR fetuses suggests the existence of a compensatory
      mechanism to maintain microcirculation within the placenta.

PMID- 9932552
TI  - Behavior-state-dependent changes in human fetal pulmonary blood flow velocity
      waveforms.
AB  - OBJECTIVE: To establish the influence of fetal behavior states on venous and
      arterial pulmonary blood flow velocity waveforms in the normally developing term
      fetus. METHODS: The relation between venous and arterial pulmonary blood flow
      velocity waveforms and fetal behavior states was investigated in 18 normal term
      fetuses. Recordings of the venous pulmonary blood flow velocity waveforms were
      obtained just proximal to the entrance in the left atrium, and the arterial
      pulmonary blood flow velocity waveforms were taken from the most proximal branch
      of the pulmonary artery in the same lung using color Doppler imaging. Time
      averaged peak systolic, peak diastolic, and end-diastolic flow velocity; peak
      systolic to peak diastolic ratio; pulsatility index; and fetal heart rate were
      calculated from both venous and arterial Doppler recordings obtained during
      behavior states 1F (quiet sleep) and 2F (active sleep). Fetal behavior states
      were determined from combined recordings of fetal eye and body movements.
      RESULTS: Recordings of sufficient quality for analysis were obtained from ten
      fetuses. Venous pulmonary blood flow velocity waveforms demonstrated a
      statistically significant increase in time-averaged peak diastolic and end
      diastolic velocity during fetal behavior state 2F. No behavior-state-related
      changes were observed for the arterial pulmonary blood flow velocity waveform.
      CONCLUSION: The data suggest an increased pressure gradient between the pulmonary
      venous system and the left atrium during behavior state 2F. Flow velocity
      waveforms from the proximal arterial pulmonary branch are independent of
      behavioral state.

PMID- 9932553
TI  - Fetal cardiac asymmetry: a marker for congenital heart disease.
AB  - OBJECTIVE: To determine the sensitivity of prenatally detected fetal cardiac
      asymmetry as a sonographic marker for congenital heart disease. METHODS: The
      normal ratios of pulmonary artery to aorta diameters and of right ventricle to
      left ventricle diameters were derived from normal fetuses scanned at 17 weeks or
      more in a 65-month period. Cross-sectional diameters of cardiac ventricles and
      great arteries were measured at the level of the valves at the time of the scan.
      Fetuses with confirmed cardiac anomalies detected prenatally during the study
      were examined to identify how many had cardiac asymmetry, determined by abnormal
      ratios. RESULTS: Linear regression analysis of the group of 881 normal fetuses
      showed the normal pulmonary artery to aorta diameter ratio remained constant
      throughout pregnancy and the normal right ventricle to left ventricle ratio
      increased slightly with progressing gestational age. The 90% confidence intervals
      were 0.79, 1.24 for the right ventricle to left ventricle ratio and 0.84, 1.41
      for the pulmonary artery to aorta ratio. Of the 73 fetuses with abnormal hearts,
      66% had either ventricular or great artery asymmetry (at least one of the two
      ratios was abnormal). However, if no asymmetry was present, the cardiac defect
      was more likely to be a minor one. CONCLUSION: Cardiac asymmetry was present in
      two-thirds of fetuses with cardiac anomalies diagnosed prenatally. If cardiac
      asymmetry is found, a more thorough examination of the fetal heart is indicated.

PMID- 9932555
TI  - C-type natriuretic peptide levels in women with gestational hypertension and
      preeclampsia.
AB  - OBJECTIVE: To measure plasma levels of C-type natriuretic peptide in women with
      normal pregnancies and those complicated by gestational hypertension and
      preeclampsia. METHODS: We collected venous plasma samples from 20 women with
      normal pregnancies, 15 with gestational hypertension, and nine with preeclampsia.
      Gestational ages ranged from 26-39 weeks. We measured C-type natriuretic peptide
      concentrations by radioimmunoassay. Statistical comparisons were made by one-way
      analysis of variance and Tukey test. RESULTS: The mean plasma concentration of C
      type natriuretic peptide in the women with normal pregnancy was 7.1 +/-2.5 pg/mL,
      in those with gestational hypertension 9.6+/-4.2 pg/mL, and in those with
      preeclampsia 8.1+/-2.4 pg/mL. There were no statistically significant differences
      between groups. The statistical power to detect a difference of 3 pg/mL at the 5%
      significance level was 78% for the group with gestational hypertension and 64%
      for the preeclamptic group. CONCLUSION: Our results suggest that C-type
      natriuretic peptide plasma levels are not significantly different in normal
      pregnancies and those complicated by gestational hypertension or preeclampsia. In
      hypertensive pregnancy disorders, C-type natriuretic peptide showed a distinct
      course compared with atrial natriuretic peptide and brain natriuretic peptide.

PMID- 9932554
TI  - Association of antibodies to beta2-glycoprotein 1 with pregnancy loss and
      pregnancy-induced hypertension: a prospective study in low-risk pregnancy.
AB  - OBJECTIVE: To determine whether higher levels of anti-beta2-glycoprotein 1 before
      25 weeks' gestation are independently associated with either pregnancy loss or
      pregnancy-induced hypertension. METHODS: Serum samples for the immunoglobulin
      (Ig) G and IgM isotypes of anti-beta2-glycoprotein 1, anticardiolipin antibody,
      and antiphosphatidylserine were collected from 325 low-risk nulliparas who
      presented for prenatal care before 25 weeks' gestation. This cohort was followed
      prospectively for the development of pregnancy loss and pregnancy-induced
      hypertension. RESULTS: The adjusted odds ratios (OR) and 95% confidence intervals
      (CI) of elevated antiphospholipid antibody levels for pregnancy loss were: IgG
      anti-beta2-glycoprotein 1, OR 1.2 (CI 0.5, 2.8); IgG anticardiolipin antibody, OR
      8.4 (CI 2.3, 31); and IgG antiphosphatidylserine, OR 5.2 (CI 1.4, 18.7). The
      relative risks of pregnancy loss for all IgG antiphospholipid antibodies were
      higher among women who had blood collected after 10 weeks' gestation compared
      with those studied before 10 weeks' gestation. However, there were only marginal
      differences in the attributable risks, suggesting that the impact of elevated
      levels of antiphospholipid antibodies might be similar in early and later stages
      of pregnancy. None of the antiphospholipid antibodies was associated with
      pregnancy-induced hypertension. CONCLUSION: In this study, elevated levels of IgG
      anticardiolipin and IgG antiphosphatidylserine antibodies were markers of
      pregnancy loss, but an elevated level of anti-beta2-glycoprotein was not a strong
      predictor of fetal loss.

PMID- 9932556
TI  - Failure of platelet angiotensin II binding to predict pregnancy-induced
      hypertension.
AB  - OBJECTIVE: To determine whether measurement of platelet angiotensin II binding at
      20 weeks' gestation identifies women destined to develop pregnancy-induced
      hypertension. METHODS: Over a 2-year period, we recruited 325 unselected,
      normotensive primigravidas from the hospital antenatal department after their
      routine 20-week scan appointments. Each woman had a singleton pregnancy, was
      normotensive at the time of entry into the study, and had an unremarkable medical
      history. Ninety-three nonpregnant women were recruited from the hospital staff
      for comparison. Platelet angiotensin II binding was measured in all participants.
      After delivery, the case notes were screened to determine pregnancy outcome.
      RESULTS: Two hundred sixty-seven women remained normotensive to delivery, 30
      developed nonproteinuric pregnancy-induced hypertension, 23 developed proteinuric
      pregnancy-induced hypertension, four had transient hypertension, and one was
      diagnosed subsequently as having essential hypertension. The median platelet
      angiotensin II binding for the nonpregnant subjects was 15.7 fmol/10(9)
      platelets, which differed significantly from the value for normotensive pregnant
      subjects (4.8 fmol/10(9) platelets, P < .001) and from the value for those who
      developed either nonproteinuric pregnancy-induced hypertension (4.95 fmol/10(9)
      platelets) or proteinuric pregnancy-induced hypertension (7.2 fmol/10(9)
      platelets, P < .001). There was no significant difference between pregnant women
      who remained normotensive and those who developed nonproteinuric or proteinuric
      pregnancy-induced hypertension. CONCLUSION: Measurement of angiotensin II binding
      in the second trimester has no value as a screening test for nonproteinuric or
      proteinuric pregnancy-induced hypertension.

PMID- 9932557
TI  - Effect of cervical carcinoma in situ and its management on pregnancy outcome.
AB  - OBJECTIVE: To assess the effect of cervical carcinoma in situ (CIS) and its
      management on subsequent pregnancy outcome. METHODS: We used a population-based
      retrospective cohort design that included record linkage between cancer data and
      birth records. The Cancer Surveillance System records of women with CIS (n =
      1851, 312 diagnosed during pregnancy) diagnosed between 1984 and 1992, were
      linked to birth certificates of their first subsequent deliveries after CIS
      diagnosis. The comparison group (n = 9201) was a random sample of women without
      CIS who gave birth during the same years. The outcome measures were preterm and
      low birth weight infants subsequent to CIS diagnosis and treatment. Treatments
      included no therapy, dilation and curettage or endocervical curettage,
      cryosurgery or laser vaporization, and conization. RESULTS: Women with CIS who
      were not treated with conization had a small increased risk of preterm delivery
      (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.0, 2.0) and no increased
      risk of low birth weight infant (OR 1.0, 95% CI 0.7, 1.6), compared with women
      without CIS, after adjusting for maternal smoking, race, parity, marital status,
      and history of induced pregnancy termination. Women with CIS who had conization
      were more likely to deliver premature infants (OR 1.6, 95% CI 1.2, 2.0) than
      women without CIS, after adjusting for the same confounding factors. The
      apparently increased risk of low birth weight (OR 1.8, 95% CI 1.4, 2.4) seemed to
      be a reflection of premature delivery. CONCLUSION: The risk of prematurity
      increased after conization for CIS and did not increase when women with CIS had
      other procedures.

PMID- 9932558
TI  - Videotaped training in alcohol counseling for obstetric care practitioners: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the feasibility of videotaped training for obstetric care
      practitioners in motivational interviewing skills that could be used in brief
      patient consultations on problem drinking. METHODS: Thirty health care
      practitioners participated in a clinical trial using a 20-minute videotape to
      instruct them in motivational interviewing. Participants engaged in a pretest
      roleplay with an actress playing a drinking pregnant woman. Those randomly
      assigned to the experimental condition watched the motivational interviewing
      videotape. Control condition participants watched a 20-minute docudrama of a
      pregnant problem drinker. Both groups then engaged in a post-test roleplay
      similar to the pretest. Behavioral ratings of the roleplays and participant
      evaluations of the motivational interviewing video constituted the outcome
      measures. RESULTS: Participant evaluations indicated that the training video was
      clear in explaining and demonstrating the principles and skills of motivational
      interviewing. Change in behavioral ratings from pretest to post-test showed
      significant differences in motivational interviewing skills between the
      experimental and control groups. Obstetric care practitioners who viewed the
      training video were rated as showing greater empathy, minimizing patient
      defensiveness, and supporting women's beliefs in their ability to change.
      CONCLUSION: Obstetric care practitioners can improve their alcohol intervention
      skills through the use of a 20-minute videotaped instruction in motivational
      interviewing. Clinicians who improve their skills in motivational interviewing
      can intervene more effectively with their drinking pregnant patients. Using
      motivational interviewing with this population holds promise for helping prevent
      alcohol-related health problems.

PMID- 9932559
TI  - Stage IA1 cervical adenocarcinoma: definition and treatment.
AB  - OBJECTIVE: To propose a definition for stage IA1 cervical adenocarcinoma, based
      on the International Federation of Gynecology and Obstetrics (FIGO) staging
      system, and to determine if patients meeting criteria might be candidates for
      conservative surgery. METHODS: Two hundred women were diagnosed with early-stage
      cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed
      by a gynecologic pathologist. Medical records were reviewed, and patients
      included in this study had microscopically identifiable lesions, up to 3 mm
      invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was
      performed. RESULTS: Twenty-one patients with microinvasive adenocarcinoma met
      criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up
      was 76 (30-172) months and median (range) patient age was 38 (24-75) years.
      Definitive treatment included type II or III radical hysterectomy in 16 cases,
      simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical
      excision procedure in one case; one patient received adjuvant pelvic radiation.
      The histologic subtypes were endocervical adenocarcinoma in 18 cases,
      adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case.
      There was no evidence of parametrial invasion or lymph node metastases in any
      patient who had radical surgery, and there were no disease recurrences.
      CONCLUSION: Patients with microinvasive adenocarcinoma who met criteria for FIGO
      stage IA1 cervical carcinoma had disease limited to the cervix, and conservative
      surgery, such as cone biopsy or simple hysterectomy, might offer them definitive
      treatment.

PMID- 9932560
TI  - Laparoscopic management of adnexal masses in premenopausal and postmenopausal
      women.
AB  - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic adnexal mass
      removal in patients without preselection for benign pathology and assess the
      operative complications and findings. METHODS: All patients presenting to the
      gynecologic oncology service between April 1992 and April 1996 with adnexal
      masses were candidates for laparoscopic management. Patients underwent
      preoperative radiological studies and office pelvic examination. Laparoscopic
      management was attempted on patients without evidence of gross metastatic disease
      or masses that extended above the umbilicus. Laparotomy was performed if
      indicated by pathologic findings or technical difficulty. All removed adnexal
      masses were sent for immediate pathologic diagnosis. The type of procedure,
      intraoperative findings, and complications were all recorded at the time of
      procedure. RESULTS: One hundred sixty patients underwent laparoscopic evaluation
      for an adnexal mass. Benign pathology was discovered in 139 (87%, 95% confidence
      interval [CI] 84, 90) patients, and 141 (88%, 95% CI 86, 91) patients were
      managed laparoscopically. Reasons for laparotomy included technical difficulty,
      operative complications, or malignancy. Frozen section diagnosis was concordant
      with the final pathology reports in all but five patients (97% concordance), and
      no discrepancies resulted in treatment delays. CONCLUSION: Laparoscopic
      management of adnexal masses can be successful in a gynecologic oncology
      population if there is expertise in operative laparoscopy, availability of
      immediate accurate pathologic examination, and appropriate further treatment
      where indicated.

PMID- 9932561
TI  - Computed tomography comparison of bony pelvis dimensions between women with and
      without genital prolapse.
AB  - OBJECTIVE: To compare bony pelvis dimensions between white women with and without
      genital prolapse using computed tomography (CT) pelvimetry. METHODS: Thirty-four
      multiparous white women with vaginal prolapse beyond the hymen and 34 matched
      white controls with no signs or symptoms of pelvic support defects underwent CT
      pelvimetry. The anteroposterior and transverse diameters of the pelvic inlet, the
      interspinous diameter of the midpelvis, and the intertuberous diameter of the
      pelvic outlet were measured. Post hoc power analysis showed that 22 women were
      needed in each group to detect a 10% difference in the pelvic dimensions between
      groups, with an alpha error of 1% and a beta error of 10%, resulting in a 90%
      power. RESULTS: Mean (+/- standard deviation [SD]) age of the subjects was 63.4+/
      8.3 years, compared with 62.9+/-7.8 years for controls. Mean parity of the
      subjects was 3.3+/-1.7, compared with 3.6+/-1.7 for controls. Mean (+/- SD)
      anteroposterior (12.5+/-1.3 versus 12.8+/-1.0 cm), interspinous (11.5+/-0.8
      versus 11.2+/-0.9 cm), and intertuberous (10.0+/-1.0 versus 9.8+/-0.8 cm)
      diameters were not significantly different between study groups. Mean transverse
      diameter of the pelvic inlet was significantly greater in women with prolapse
      than those without prolapse (12.9+/-0.7 versus 12.4+/-0.6 cm, P = .006).
      CONCLUSION: Women with advanced vaginal prolapse have larger transverse inlet
      diameters than do women with normal pelvic support.

PMID- 9932563
TI  - Reading skills and family planning knowledge and practices in a low-income
      managed-care population.
AB  - OBJECTIVE: To examine the relationship between reading ability and family
      planning knowledge and practices among Medicaid managed care enrollees. METHODS:
      A total of 406 women age 19-45 years enrolled in TennCare and members of
      Prudential HealthCare Community Plan in Memphis, Tennessee were interviewed to
      determine their methods of contraception, desire for additional information about
      contraceptives, and knowledge about the time in menstrual cycle they are at
      highest risk for pregnancy. Patient reading ability was assessed by an
      abbreviated version of the Test of Functional Health Literacy of Adults. The
      independent associations between reading ability, desire for additional
      contraceptive information, and knowledge about the highest risk time for
      pregnancy were assessed with logistic regression. RESULTS: Almost 10% of the
      respondents had low reading skills. Women who had used an intrauterine device,
      douching, rhythm, or levonorgestrel implants as methods of birth control had
      higher rates of low reading skills than women who used other methods of birth
      control. Compared with women with good reading skills, women with low reading
      skills were 2.2 times (95% confidence interval [CI] 1.1, 4.4) more likely to want
      to know more about birth control methods and 4.4 times (95% CI 2.2, 9.0) more
      likely to have incorrect knowledge about when they were most likely to get
      pregnant. These relationships were significant even after controlling for age,
      race, and marital status. CONCLUSION: Health providers and organizations that
      serve historically underserved populations must understand that some individuals
      have a low level of reading ability that limits family planning education.

PMID- 9932562
TI  - Bone mineral density in women using depot medroxyprogesterone acetate for
      contraception.
AB  - OBJECTIVE: To evaluate the possible effects of depot medroxyprogesterone acetate
      injectable contraception on bone mineral density in reproductive-age women.
      METHODS: We conducted a population-based cross-sectional comparison of bone
      mineral density levels in women using depot medroxyprogesterone acetate
      contraception and in women of similar age not using this method. The study
      recruited 457 nonpregnant women aged 18-39 years who were enrollees of a
      Washington state health maintenance organization. One hundred eighty-three women
      were receiving injections and 274 were not. Bone mineral density at several
      anatomic sites (spine, femoral neck, greater trochanter, and whole body) was
      measured using dual-energy x-ray absorptiometry. Data on other factors
      potentially related to bone density were collected through questionnaire and
      examination. RESULTS: Overall, age-adjusted mean bone density levels were lower
      for users of this method than for nonusers at all anatomic sites: The mean
      difference was 2.5% for the spine (P = .03) and 2.2% for the femoral neck (P =
      .12). Exposure to depot medroxyprogesterone acetate continued to be significantly
      (P < .01) associated with decreased bone density at the femoral neck, spine, and
      trochanter after multivariate adjustment for other risk factors related to bone
      density. Age-specific comparisons indicated that the major differences in bone
      density between users and nonusers occurred in the youngest age group (women 18
      21 years); the mean femoral neck bone density was 10.5% lower (P < .01) for the
      exposed women, and differences were consistent (P < .01) across all anatomic
      sites. We also noted a significant dose-response relation between longer use of
      depot medroxyprogesterone acetate and decreased bone density levels in this age
      group (P < .01 for all sites). CONCLUSION: These results provide evidence that
      contraception with depot medroxyprogesterone acetate, particularly long-term use,
      may adversely affect bone mineral density levels in young women aged 18-21 years.
      The implications for future bone health need further study.

PMID- 9932564
TI  - Grief, depression, and coping in women undergoing infertility treatment.
AB  - OBJECTIVE: To identify the levels of grief and depression and the coping
      mechanisms of women with infertility problems who participated in in vitro
      fertilization (IVF) or ovulation-induction medication. METHODS: Pretest and post
      test data were obtained from 50 IVF and 50 ovulation-induction medication
      patients receiving treatment at two urban infertility centers. RESULTS: Both
      groups of women experienced measurable levels of grief and depression before,
      during, and after treatment. Higher scores on the Grief Experience Inventory were
      found for both groups of women when pregnancy did not occur. Age, reproductive
      problems, years infertile, financial impact, and number of past IVF cycles were
      not found to influence the reported grief or depression levels. Women in the IVF
      and ovulation-induction medication groups used isolation coping behaviors such as
      self-talk and sleep. CONCLUSION: Because of moderate to high levels of grief and
      depression, therapeutic counseling may be more effective if initiated before the
      infertility treatment. Women's present levels of distress and coping strategies
      should be assessed prior to initiating infertility treatment to provide the
      patients with opportunities to learn and practice new adaptive behaviors that
      could enhance their ability to cope with infertility and the associated medical
      procedures.

PMID- 9932565
TI  - Infertility treatment and informed consent: current practices of reproductive
      endocrinologists.
AB  - OBJECTIVE: To determine current practice patterns of obtaining informed consent
      for infertility treatment by reproductive endocrinologists and to assess changes
      in response to reports of an association between ovulation induction and ovarian
      cancer. METHODS: Board-certified reproductive endocrinologists (n = 575) were
      surveyed by mail regarding how they informed patients and obtained consent for
      infertility treatments and how their practices had been influenced by studies
      suggesting a link between ovulation induction and ovarian cancer. Data were
      analyzed using chi2 and logistic regression analyses. RESULTS: The return rate
      was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with
      physicians to inform their patients of risks and benefits of all infertility
      treatments. Additional means, such as audiovisual aids, were used significantly
      more often for assisted reproductive technologies (including intracytoplasmic
      sperm injection and use of donated eggs) than for less invasive therapies (31-43%
      versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for
      hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal
      written consent was used significantly more often for the various assisted
      reproductive technologies than for hysterosalpingogram, intrauterine
      insemination, or ovulation induction (94-95% versus 26-44%). Although most
      physicians (70%) did not believe that ovulation induction increases the risk of
      ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported
      changing their practices since an association was reported. Common changes
      included limiting length of treatment and addressing ovarian cancer risk.
      CONCLUSION: Current practice patterns of obtaining informed consent for various
      infertility treatments by board-certified reproductive endocrinologists show, as
      expected, that informed consent is more rigorous for assisted reproductive
      technologies. Although most surveyed did not believe that ovulation induction
      increases risk of ovarian cancer, the majority of physicians addressed that risk
      when obtaining consent and nearly half changed their practices on the basis of a
      possible association.

PMID- 9932566
TI  - Continuous combined hormone replacement therapy compared with tibolone.
AB  - OBJECTIVE: To compare relief of vasomotor symptoms, changes in lipoproteins, and
      bleeding patterns in postmenopausal women receiving either continuous combined
      hormone replacement therapy (HRT) of estradiol valerate and norethisterone or
      tibolone 2.5 mg/day. METHODS: In a multicenter, randomized, open-label study, 235
      postmenopausal women received one of the above-mentioned treatments. Fasting
      lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit,
      participants completed Greene climacteric questionnaires and recorded any
      bleeding episodes. Data are presented as mean +/- standard deviation if normally
      distributed, median and interquartile range if non-normally distributed, or as
      frequency count. For menopausal symptoms and diary card data, the differences
      were tested by Wilcoxon rank-sum test. RESULTS: One hundred sixteen women
      received continuous combined HRT and 119 women received tibolone; 72 and 76
      women, respectively, completed 12 months of therapy. Both treatments effectively
      relieved vasomotor symptoms and reduced serum total cholesterol. Continuous
      combined HRT, but not tibolone, significantly reduced low-density lipoprotein
      levels. Both treatments reduced high-density lipoprotein levels, but the effect
      was more profound with tibolone. The initial bleeding score was higher for women
      taking continuous combined HRT; however, by the end of the study, the percentages
      of amenorrheal women were comparable. Endometrial histology was similar for both
      treatments at the end of the study, although two cases of proliferative
      endometrium were found in the tibolone group. CONCLUSION: Estradiol valerate
      norethisterone continuous combined HRT controls symptoms and is associated with a
      safe lipid profile.

PMID- 9932567
TI  - Localization and sex steroid regulation of androgen receptor gene expression in
      rhesus monkey uterus.
AB  - OBJECTIVE: To characterize the cellular sites and hormonal regulation of uterine
      androgen receptor gene expression in the monkey. METHODS: Ovariectomized rhesus
      monkeys (five in each group) were treated with placebo (the control group),
      estradiol (E2), E2 plus progesterone, or E2 plus testosterone by sustained
      release pellets administered subcutaneously. After 3 days of treatment, uteri
      were removed and uterine sections were analyzed by in situ hybridization for
      androgen receptor messenger RNA (mRNA). RESULTS: Androgen receptor mRNA was
      detected in endometrial stromal cells and myometrial smooth muscle cells, with
      lesser expression in endometrial epithelial cells. Both E2 and E2 plus
      progesterone treatment doubled androgen receptor mRNA levels in stromal cells (P
      < .01), whereas E2 plus testosterone treatment increased stromal androgen
      receptor mRNA levels by about five-fold (P < .001) compared with placebo
      treatment. In the endometrial epithelium, E2 alone did not increase androgen
      receptor mRNA levels significantly. However, the E2 plus progesterone and E2 plus
      testosterone treatments increased epithelial androgen receptor mRNA levels by 4.3
      and 5 times, respectively (P = .008 and P < .002, respectively). Androgen
      receptor mRNA was distributed homogeneously in smooth muscle cells across the
      myometrium. Estradiol treatment alone did not increase myometrial androgen
      receptor mRNA levels significantly, but the E2 plus progesterone and E2 plus
      testosterone treatments increased myometrial androgen receptor mRNA levels by 1.8
      and 2 times, respectively (P = .001 and P < .001, respectively). CONCLUSION:
      Androgen receptor gene expression was detected in all uterine cell compartments
      where it was subject to significant sex steroid regulation. The fact that
      androgen receptor mRNA levels were consistently up-regulated by a combined E2
      plus testosterone treatment while E2 treatment alone had little or no effect
      shows that a collaborative action of E2 and testosterone enhances androgen
      receptor expression in the monkey uterus.

PMID- 9932568
TI  - A randomized comparison of extra-amniotic saline infusion and intracervical
      dinoprostone gel for cervical ripening.
AB  - OBJECTIVE: To compare extra-amniotic saline infusion to intracervical
      dinoprostone gel for preinduction cervical ripening. METHODS: Women with Bishop
      scores less than 5 were assigned randomly to either extra-amniotic saline
      infusion (n = 26) or intracervical dinoprostone gel (n = 26) for preinduction
      cervical ripening. A sample size of 50 would have 80% power to detect a 10-hour
      difference in the mean time from start of cervical ripening to delivery for the
      two methods of intervention, with a type I error of .05. RESULTS: The study
      populations were similar in age, gestational age, and initial Bishop score. They
      differed in parity, with 22 nulliparas in the extra-amniotic saline infusion
      group versus 13 in the dinoprostone gel group (relative risk [RR] 1.69, 95%
      confidence interval [CI] 1.11, 2.57). The number of women achieving a favorable
      Bishop score at 6 hours was greater with extra-amniotic saline infusion (n = 20)
      than dinoprostone gel (n = 9) (RR 2.14, 95% CI 1.22, 3.75). Mean time from start
      of ripening to delivery was 25.9 hours with extra-amniotic saline infusion and
      30.2 hours with dinoprostone gel (P = .25). Birth weight, Apgar scores, umbilical
      artery pH, and infectious morbidity were similar between groups. CONCLUSION: More
      women achieved a favorable Bishop score at 6 and 12 hours after the start of
      cervical ripening with extra-amniotic saline infusion compared with dinoprostone
      gel. Saline infusion is as safe as dinoprostone gel for preinduction cervical
      ripening.

PMID- 9932569
TI  - Comparison between oral and vaginal administration of misoprostol on uterine
      contractility.
AB  - OBJECTIVE: To compare the degree of absorption and the effect on uterine
      contractility of the prostaglandin E1 analogue misoprostol after vaginal and oral
      administration. METHODS: Thirty women with a normal intrauterine pregnancy
      between 8 and 11 weeks' gestation who requested termination of pregnancy were
      given either 0.2 mg (orally n = 5; vaginally n = 6) or 0.4 mg (orally n = 10;
      vaginally n = 9) of misoprostol. Intrauterine pressure was recorded using a Grass
      polygraph connected to a pressure transducer 30 minutes before misoprostol was
      given and for 4 hours thereafter. At the end of the recording, suction curettage
      was performed. Blood samples were obtained at 0, 0.5, 1, 2, 4, and 6 hours for
      measurement of misoprostol, which was assayed by high-pressure liquid
      chromatography-mass spectrometry. RESULTS: In all patients, the first effect was
      an increase in uterine tonus. After 0.4 mg of misoprostol administered orally,
      uterine tonus started to increase after a mean (+/- standard deviation) time of
      7.8+/-3.0 minutes and reached its maximum after 25.5+/-5.0 minutes. The
      corresponding times after vaginal administration were 20.9+/-5.3 minutes and
      46.3+/-20.7 minutes, respectively. The initial increase in tonus was also more
      pronounced after oral than after vaginal administration. After vaginal
      administration, all patients developed uterine contractions; the activity,
      measured in Montevideo units, increased continuously during the observation
      period. This was not the case after oral administration. Plasma levels of
      misoprostol were measured in 18 patients. The highest levels were found 30
      minutes after oral treatment and 1-2 hours after vaginal administration.
      CONCLUSION: The long-lasting and continuously increasing uterine contractility
      after vaginal administration can be explained only in part by a direct effect of
      misoprostol. The longer period of elevated plasma levels of misoprostol may also
      have initiated the prolonged events leading to increased uterine contractility.

PMID- 9932570
TI  - Station and cervical dilation at epidural placement in predicting cesarean risk.
AB  - OBJECTIVE: To compare station and cervical dilation at the time of epidural
      placement for predicting cesarean delivery risk. METHODS: This prospective cohort
      study included 275 women in labor with live, singleton fetuses at term in vertex
      presentations. We excluded women with preeclampsia or previous cesarean
      deliveries. A multiple logistic regression model evaluated demographic and labor
      related variables' associations with cesarean risk. RESULTS: Fifty-nine of the
      275 patients receiving epidural analgesia (21.5%) were delivered by cesarean,
      whereas 216 (78.5%) delivered vaginally. Variables that proved to be
      statistically significant in increasing the likelihood of cesarean were station
      at time of epidural placement (odds ratio [OR] 5.3; 95% confidence interval [CI]
      2.6, 11.0; P < .001) and nulliparity (OR 3.8, 95% CI 1.8, 8.0; P < .001).
      Cervical dilation at the time of epidural placement was not a statistically
      significant predictor (OR 1.2, 95% CI 0.9, 1.6; P = .26). Cesareans were
      performed in 43 of 129 women (33.3%) who received epidurals with the vertex at a 
      1 station or higher, whereas only 16 of 146 women (11.0%) had cesareans if
      placement of the epidural was done after the vertex had reached at least a zero
      station. CONCLUSION: Station at the time of epidural placement was more accurate
      predicting cesarean risk than cervical dilation. Placement of the epidural after
      the fetal vertex has become engaged in the pelvis (at least a zero station)
      resulted in a substantially lower cesarean risk.

PMID- 9932571
TI  - Predictive value of electronic fetal monitoring for intrapartum fetal asphyxia
      with metabolic acidosis.
AB  - OBJECTIVE: To determine the predictive value of each fetal heart rate (FHR)
      variable and of patterns of FHR variables for fetal asphyxia during labor.
      METHODS: This matched case-control study included an asphyxia group of 71 term
      infants with umbilical artery base deficit greater than 16 mmol/L and a control
      group of 71 term infants with umbilical artery base deficit less than 8 mmol/L.
      Each FHR record available for the 4 hours before delivery was scored in 10-minute
      cycles for each FHR variable. Selected patterns of important FHR variables were
      examined during the last hour before delivery for their predictive value for
      fetal asphyxia. RESULTS: The FHR variables associated with fetal asphyxia
      included absent and minimal baseline variability and late and prolonged
      decelerations. Fetal heart rate patterns with absent baseline variability were
      the most specific but identified only 17% of the asphyxia group. The sensitivity
      of this test increased to 93% with the addition of less specific patterns. The
      estimated positive predictive value ranged from 18.1% to 2.6%, and the negative
      predictive value ranged from 98.3% to 99.5%. CONCLUSION: A narrow 1-hour window
      of FHR patterns including minimal baseline variability and late or prolonged
      decelerations will predict fetal asphyxial exposure before decompensation and
      newborn morbidity. Thus, with careful interpretation, predictive FHR patterns can
      be a useful screening test for fetal asphyxia. However, supplementary tests are
      required to confirm the diagnosis and to identify the large number of false
      positive patterns to avoid unnecessary intervention.

PMID- 9932572
TI  - Group B streptococcus infection rate unchanged by gestational diabetes.
AB  - OBJECTIVE: Group B streptococcal colonization in pregnancy has been associated
      with adverse perinatal outcomes, including intra-amniotic infection, postpartum
      endometritis, and neonatal sepsis. We sought to determine whether gestational
      diabetes increases the risk of maternal and neonatal morbidity from group B
      streptococcal colonization. METHODS: Gestational diabetic and nondiabetic women
      who underwent vaginal or anogenital culture for group B streptococcus
      colonization in pregnancy were followed up for pregnancy outcome. Antibiotic
      prophylaxis was not routinely given. Major perinatal morbidity included
      intraamniotic infection, endometritis, and neonatal sepsis. Potential confounding
      variables included induction of labor, cesarean delivery, prematurity, maternal
      antibiotic use, and prolonged rupture of membranes. RESULTS: We compared 446
      gestational diabetic women to 1,046 nondiabetic women for outcome. Overall, 12%
      were colonized with group B streptococcus, with no difference in colonization
      rates between gestational diabetic (12%) and nondiabetic (12%) women. There were
      no differences in intraamniotic infection rates between gestational diabetic and
      nondiabetic women, whether group B streptococcus positive (16% compared with 13%)
      or group B streptococcus negative (10% compared with 11%). Likewise, endometritis
      did not differ (6-9%) regardless of diabetes or group B streptococcus status.
      Neonatal sepsis was higher in group B streptococcus-positive women overall (3%
      compared with 1%, odds ratio 3.71, 95% confidence interval 1.23, 10.81), but did
      not differ between diabetic and nondiabetic pregnancies. CONCLUSION: Gestational
      diabetes does not alter the perinatal morbidity associated with group B
      streptococcal colonization in pregnancy.

PMID- 9932573
TI  - Intrauterine light probe for photodynamic ablation therapy.
AB  - BACKGROUND: Endometrial ablation by means of photodynamic therapy is currently
      being evaluated as an outpatient treatment for dysfunctional uterine bleeding.
      Photodynamic therapy requires the activation of a photosensitizer by laser light.
      We describe a new device specifically designed to provide light delivery to the
      uterus for endometrial photodynamic therapy. INSTRUMENT: The intrauterine light
      probe consists of the three flexible optical fibers converging to one bundle
      resembling the shape of the uterine cavity. Each of the fibers contains a
      cylindrical light diffuser. EXPERIENCE: The intrauterine light probe was tested
      in removed human uteri for its capability to distribute light in a tissue
      simulating scattering medium and to deliver sufficient light throughout the
      endometrium. The light distribution of the intrauterine light probe in the
      scattering medium is uniform on eight axes tested around the diffusing fibers.
      The pattern of light distribution in human uteri is similar to that in the
      medium. At the endomyometrial junction, there is still one third of the light
      applied to the endometrial surface whereas deeper in the myometrium, the light
      power drops to less than 10%. CONCLUSION: We propose a device that will deliver
      light to the uterine cavity to induce endometrial ablation by means of
      photodynamic therapy.

PMID- 9932574
TI  - Ethical challenges in the managed practice of obstetrics and gynecology.
AB  - Obstetrics and gynecology has been transformed from a fee-for-service, unmanaged
      system to a prepaid managed system. This change poses significant ethical
      challenges, which we address. We show that obstetrician-gynecologists and medical
      institutions are moral co-fiduciaries of female and pregnant patients, that the
      obstetrician-gynecologist should be economically disciplined without capitulating
      to managed care, and that managed care organizations have an obligation to
      support the medical education and research from which they benefit.

PMID- 9932575
TI  - Development of a national course on research methodology for Canadian residents
      in obstetrics and gynecology.
AB  - OBJECTIVE: To report our experience developing and implementing an introductory
      course on research methods for Canadian obstetrics and gynecology residents.
      METHODS: A program entitled "An Introduction to Research," originating at Queen's
      University, developed into an annual series of regional courses across Canada,
      under the auspices of the Association of Professors of Obstetrics and Gynaecology
      of Canada. Didactic lectures, interactive workshops, and online computer
      demonstrations introduced participants to the basic elements of clinical
      research. RESULTS: Since its inception, over 1000 participants have attended the
      program. Nearly all of the 296 respondents to a course evaluation agreed that the
      program was well organized, presented material at an appropriate level, and was
      useful. CONCLUSION: This course ensured that residents in obstetrics and
      gynecology across Canada were given a basic level of research training, as
      required by the Royal College of Physicians and Surgeons of Canada.

PMID- 9932576
TI  - The Zavanelli maneuver: 12 years of recorded experience.
AB  - OBJECTIVE: To evaluate the applicability and safety of the Zavanelli maneuver
      (manual return to the vagina of the partially born but undeliverable fetus with
      subsequent extraction by cesarean). DATA SOURCES: MEDLINE computer database,
      Science Citation Index, and Index Medicus, 1985 through 1997 using the search
      terms Zavanelli maneuver, cephalic replacement, abdominal rescue, head
      entrapment, and shoulder dystocia. METHOD OF STUDY SELECTION: Efforts to return
      103 partially born but undeliverable fetuses to the uterus have been reported in
      30 publications since the first case was reported in 1985. All cases were
      accepted for review, successful or not. TABULATION, INTEGRATION, AND RESULTS:
      Clinically relevant features were extracted from each case report. In 92 cases,
      fetuses presented by the vertex. Cephalic replacement was successful in 84 of
      those. In 11 cases, the fetus presented by the breech. Podalic replacement was
      successful in all of those. Seven women suffered tissue-disruptive trauma. There
      were no maternal deaths or fetal injuries ascribed to the maneuver. CONCLUSION:
      The 92% overall success rate is remarkable for a new procedure; even more
      noteworthy, in most cases it was applied by operators with no experience with it,
      and for cephalic replacement, it was used only after conventional maneuvers had
      failed. Using it early in the treatment of obstructed partial vaginal delivery is
      recommended.

PMID- 9932577
TI  - Predicting risk of complications with gynecologic laparoscopic surgery.

PMID- 9932578
TI  - Preoperative serum hCG level and intraoperative failure of laparoscopic linear
      salpingostomy for ectopic pregnancy.

PMID- 9932579
TI  - Preoperative serum hCG level and intraoperative failure of laparoscopic linear
      salpingostomy for ectopic pregnancy.

PMID- 9932580
TI  - The cost-effectiveness of routine type and screen admission testing for expected
      vaginal delivery.

PMID- 9932581
TI  - Measuring the indirect and direct costs of acute otitis media.
AB  - OBJECTIVES: To test a method of measuring the related cost of acute otitis media
      (AOM) and to provide a preliminary calculation of the indirect and directs costs
      associated with a single, medically treated episode of AOM. DESIGN: The Otitis
      Media Diary was used to measure indirect and direct costs associated with AOM in
      a prospective cohort study. Measured values included the parental time spent in
      otitis-specific child care and the number and type of medications used. A
      previously developed economic model was used to calculate the monetary costs
      associated with the value of caregiver time and the total opportunity cost of
      AOM. SETTING: The pediatric clinic of Madigan Army Medical Center, Tacoma, Wash.
      PATIENTS: A cohort of 25 children (12 with AOM and 13 controls) aged 1 to 3
      years. MAIN OUTCOME MEASURES: Caregiver time and medication use. RESULTS: The
      total cost attributable to AOM in the 3-month period following diagnosis was
      $1330.58 (95% confidence interval, $1008.75-$1652.43), with the majority of that
      cost stemming from the indirect, rather than direct, costs of illness. After
      conservative estimates of unmeasured expenses, such as clinic visits and
      transportation, were accounted for, indirect costs, accrued primarily by parental
      time, accounted for nearly 90% (95% confidence interval, 87.1%-92.3%) of the
      total 3-month cost associated with AOM and its medical treatment. The cost items
      of the Otitis Media Diary were also highly correlated with each other and with
      other measures of clinical and functional health status. CONCLUSIONS: Otitis
      Media Diary measures of parental time and medication use appear to provide a more
      accurate means of calculating the real social costs attributable to the AOM
      disease process in this cost-effectiveness analysis.

PMID- 9932582
TI  - An update on the treatment of hemangiomas in children with interferon alfa-2a.
AB  - OBJECTIVE: To report the benefits and complications of subcutaneous interferon
      alfa-2a therapy for hemangiomas in children. DESIGN: Prospective nonrandomized
      trial. SETTING: Tertiary care pediatric referral center. PATIENTS: Twenty-four
      pediatric patients diagnosed with massive or life-threatening hemangiomas.
      INTERVENTIONS: Each patient received daily subcutaneous injections of interferon
      alfa-2a to a target dose of 3 million U/m2 of body surface area for a minimum of
      4 months. Nineteen patients completed therapy and have received adequate follow
      up. MAIN OUTCOME MEASURES: Clinical and radiographic comparisons before, during,
      and after therapy. Reduction in hemangioma size was graded as complete (>90%),
      substantial (50%-80%), intermediate (20%-40%), or no response (<10%). RESULTS:
      Mean age at institution of therapy was 9.6 months, and mean duration of treatment
      was 10.2 months. Most patients (70%) had not received prior therapy. Responses
      were as follows: complete, 8 patients (42%); substantial, 3 patients (16%),
      intermediate, 5 patients (26%); and no response, 3 patients (16%) (n = 19).
      During therapy, 5 patients (26%) developed neurological abnormalities: 3 had an
      unsteady gait, and 2 had fine motor deficits. Only 1 of these 5 patients required
      premature termination from the study, and the neurological abnormalities in all 5
      patients resolved after treatment was discontinued. Two of the 4 patients with
      neurological findings who completed therapy demonstrated complete resolution of
      their hemangiomas. Patients who developed neurological abnormalities began
      interferon alfa-2a therapy at an earlier age (4.7 months) than patients without
      neurological difficulties (aged 11.1 months). The mean time from initiation of
      therapy to the appearance of neurological complications was 4.8 months.
      CONCLUSIONS: In pediatric patients with massive or life-threatening hemangiomas,
      interferon alfa-2a therapy is an effective treatment option. However,
      neurological evaluation before and during therapy with interferon alfa-2a should
      be performed owing to a significant incidence of neurological abnormalities
      (28%). Although all children with neurological findings demonstrated neurological
      recovery after discontinuation of therapy, we have changed our protocol and now
      more gradually increase the dosage of interferon alfa-2a up to 3 million U/m2 per
      day. The effect of this modification on the development of neurological
      abnormalities has not yet been determined.

PMID- 9932583
TI  - Potential pitfalls of initiating a newborn hearing screening program.
AB  - OBJECTIVE: To examine the efficacy of a universal screening program for infant
      hearing. DESIGN: Retrospective analysis. SETTING: Tertiary care center. PATIENTS:
      We examined 2289 (90.2%) of 2537 infants born at our institution from April 1,
      1995, to June 30, 1996, for hearing loss (HL). INTERVENTIONS: We used a 3-stage
      protocol with transient evoked otoacoustic emissions (TEOAE) in stages 1 and 2
      and diagnostic evaluation in stage 3. Infants without reproducible TEOAEs in
      either ear after stage 2 were referred to stage 3. MAIN OUTCOME MEASURES:
      Specificity of TEOAE, incidence of HL, prevalence of risk factors for HL, cost of
      TEOAE screening, and identification of barriers to universal screening. RESULTS:
      Of the infants undergoing TEOAE screening, 91.1% passed stage 1. Of infants
      needing repeated testing, 73.7% passed and 26.2% failed. Of the 43 infants
      referred for diagnostic evaluation, 5 (11.6%) had HL. The combined incidence of
      conductive and sensorineural HL was 2.18 per 1000 newborns. The prevalence of at
      least 1 risk factor for HL was 10.4%. The estimated cost of TEOAE screening was
      $24.48 per infant. Ten percent of infants did not undergo screening due to
      program deficiencies. CONCLUSIONS: Screening with TEOAE was sufficiently specific
      for universal screening. However, we were unable to achieve truly universal
      screening. This is probably the reason for our lower incidence of sensorineural
      HL. We were unable to continue our universal newborn screening program, due to
      lack of funding, difficulties with program implementation, and our low incidence
      of detected HL.

PMID- 9932584
TI  - The CHARGE association: the role of tracheotomy.
AB  - OBJECTIVES: To evaluate the need for a tracheotomy and its timing during the
      evolution of an association of malformations, including coloboma, heart defects,
      choanal atresia, developmental and growth retardation, genitourinary
      malformation, and ear anomalies (CHARGE association). DESIGN: Retrospective study
      from January 1988 through December 1997. SETTING: Four academic tertiary care
      centers. PATIENTS AND METHODS: Forty-five patients with CHARGE association having
      at least 3 cardinal malformations (growth retardation excluded) and review of the
      malformations and respiratory manifestations encountered. All the patients
      underwent endoscopic exploration on several occasions. We reviewed the nature and
      the timing of therapeutic interventions performed on the airway. RESULTS: Two
      patients died (one patient of septicemia, the other of unknown causes).
      Abnormalities of blood gas levels and/or sleep were found in 30 patients (67%),
      were responsible for cardiorespiratory arrest in 9 (20%), and required admission
      to the intensive care unit in 21 (47%). Pharyngolaryngeal anomalies leading to
      dyspnea (discoordinate pharyngolaryngomalacia, glossoptosis, retrognathia,
      laryngeal paralysis, cleft, stenosis, and difficult intubation) were found in 26
      patients (58%). Tracheobronchial anomalies (esophagotracheal fistula, esophageal
      atresia, and tracheomalacia) were present in 18 patients (40%). Resection of the
      aryepiglottic folds was attempted 3 times, but without success. Tracheotomy was
      necessary in 13 patients (29%) at a median age of 2.4 months (mean duration, 25
      months). Among these infants, the posterior nasal choanae were patent in 10
      patients at the time of tracheotomy. Gastroesophageal reflux was encountered in
      36 patients (80%). Prolonged enteral feeding was necessary in 21 patients (47%),
      with gastrostomy in 16 (of whom 9 needed a tracheotomy). These feeding
      difficulties and airway problems were highly correlated. CONCLUSIONS: We
      encountered multiple, complicated airway abnormalities. Resection of
      aryepiglottic folds was inadequate. Often, a tracheotomy could not be avoided in
      these patients, regardless of choanal patency. Tracheotomy needs to be performed
      early to avoid hypoxic events. In some selected patients, ventilation using
      bilevel positive airway pressure may be an alternative.

PMID- 9932585
TI  - Pediatric myofibromatosis of the head and neck.
AB  - OBJECTIVES: To examine the clinical and pathological features of pediatric
      myofibroma of the head and neck and to discuss the challenges in diagnosis and
      treatment. DESIGN: A retrospective search of pathology department and clinical
      records to identify patients with myofibroma and a retrospective review of
      English-language medical publications. SETTING: Academic medical center.
      PATIENTS: Thirteen pediatric patients (aged from birth to 8 years old) diagnosed
      as having myofibroma of the head and neck. RESULTS: Nine of 13 patients were
      cured with conservative surgical excision. Four patients (31%) had recurrence,
      requiring multiple surgical procedures. One third showed spontaneous regression
      clinically or by histological examination. The clinical course did not parallel
      the histological appearance, as high cellularity and mitotic figures were
      commonplace among the specimens. A misdiagnosis of malignancy was not unusual in
      this series, as 3 patients had an initial diagnosis of fibrosarcoma, which on
      review was revised to myofibroma. CONCLUSIONS: Myofibromatosis is a distinct
      disorder among the great number of fibrous proliferations occurring in infants
      and children, with a particular predilection for the head and neck region. These
      lesions should be clearly distinguished from conventional adult-type fibromatoses
      (desmoid tumors), which are more aggressive. Most patients have solitary lesions
      that respond well to conservative surgical excision, whereas a few of these
      lesions behave more aggressively, requiring several surgical procedures for the
      management of recurrent or persistent tumor. Many of these lesions show
      spontaneous regression, suggesting that lesions not affecting vital functions,
      resulting in growth anomalies, or demonstrating rapid aggressive growth may be
      managed conservatively.

PMID- 9932587
TI  - Oropharyngeal manifestations of lepidopterism.
AB  - OBJECTIVE: To describe previously unreported oropharyngeal manifestations and
      management of caterpillar ingestion. DESIGN: Retrospective case series. SETTING:
      Tertiary children's hospital. PATIENTS: A total of 733 cases of exposure to
      caterpillars from January 1, 1994, to November 1, 1997, were reviewed. Twenty-six
      patients had oropharyngeal exposure with 8 patients ingesting the caterpillar.
      Ages ranged from 7 months to 7 years with 14 boys and 12 girls. INTERVENTIONS:
      All patients had a thorough examination of the oropharynx for caterpillar spines.
      For children who ingested a caterpillar, direct laryngoscopy, bronchoscopy, and
      esophagoscopy with removal of caterpillar spines were performed. RESULTS: At the
      point of caterpillar contact, buried caterpillar spines with focal erythema were
      observed. The lips, tongue, and buccal mucosa were the most frequently involved
      areas. The esophagus was involved in 8 of the patients. No postoperative
      complications were noted. CONCLUSION: With individualized care and prompt removal
      of venomous caterpillar spines, complications are not likely to result from
      caterpillar ingestion.

PMID- 9932586
TI  - High angiogenic activity in cells isolated from cystic hygroma: role of bFGF.
AB  - BACKGROUND: Cystic hygromas are characterized by a proliferation of small vessels
      and lymphatics with intervening fibrous tissue. Studies have shown malignant
      tumors and some benign neoplasms are dependent on angiogenesis, the induction of
      new capillaries from preexisting vessels. Growth and progression of these tumors
      are associated with a disturbance in the balance of angiogenic inducers and
      inhibitors. We have postulated that cells derived from cystic hygromas are
      angiogenic due to secretion of higher levels of angiogenic inducers that promote
      vascular proliferation. DESIGN: A large cystic mass was surgically removed and a
      portion of the sterile tumor was immediately placed in the medium. The tissue was
      minced, washed in phosphate-buffered saline, and grown to near confluence.
      Conditioned medium was collected under serum-free conditions after 48 hours.
      Secreted proteins were concentrated, quantitated, and analyzed in an in vitro
      endothelial cell migration assay and by Western blot. Antibody to factor VIII
      related antigen was performed to confirm endothelial cell origin of the cultured
      cells. MAIN OUTCOME MEASURES: In vitro angiogenic activity of secreted proteins
      in a capillary endothelial migration assay was tested by using blocking
      antibodies to angiogenic inducer, basic fibroblast growth factor, and angiogenic
      inhibitor, thrombospondin-1. Total protein levels of thrombospondin-1 were
      determined by Western blot. RESULTS: Cells isolated from cystic hygroma are
      angiogenic in vitro and this angiogenic activity is due to secretion of high
      levels of angiogenic inducer, basic fibroblast growth factor, and lower levels of
      naturally occurring angiogenic inhibitor, thrombospondin-1. CONCLUSIONS: Cystic
      hygromas may represent another neoplasm dependent on angiogenesis. The angiogenic
      activity is due in part to elevated levels of potent angiogenic inducer, basic
      fibroblast growth factor. Antiangiogenic therapy directed at the endothelial cell
      may help suppress the growth of cystic hygromas.

PMID- 9932588
TI  - Relationship between uninasal anatomy and uninasal olfactory ability.
AB  - OBJECTIVE: To examine the relationship between uninasal anatomy and olfactory
      ability. DESIGN: A stepwise analysis of variance was used to regress the
      logarithm of the percentage of correct responses on the Odorant Confusion Matrix
      (a measure of olfactory ability) against the logarithm of nasal volume
      measurements determined from computed tomographic scans. PARTICIPANTS: Nineteen
      patients with hyposmia whose olfactory losses were thought to be related to
      conductive disorders. RESULTS: After correcting for sex differences, a
      mathematical model was developed in which the volume of 6 regions of the nasal
      cavity, 6 first-order interactions, and 3 second-order interactions accounted for
      97% of the variation in the measure of olfactory ability. CONCLUSIONS: Increases
      in the size of compartments of the nasal cavity around the olfactory cleft
      generally increase olfactory ability. Also, anatomical differences in the nasal
      cavities of men and women may account, in part, for sex differences in olfactory
      ability.

PMID- 9932589
TI  - Endoscopic endonasal repair of orbital floor fracture.
AB  - BACKGROUND: High-resolution endoscopes and the advent of endoscopic instruments
      for sinus surgery provide surgeons with excellent endonasal visualization and
      access to the orbital walls. OBJECTIVE: To demonstrate repair of orbital floor
      blowout fractures through an intranasal endoscopic approach that allows repair of
      the orbital floor fracture and elevation of the orbital content using a balloon
      catheter without an external incision. DESIGN: This study was a retrospective
      analysis of 11 patients who underwent surgical repair of orbital floor fractures
      from September 1994 to June 1997. There were 10 male patients and 1 female
      patient, aged 12 to 32 years (mean age, 24 years). These patients had undergone
      primary repair of pure orbital blowout fractures and were followed up at least 6
      months after surgery. RESULTS: There were no intraoperative or postoperative
      complications. Nine patients showed a complete improvement of their diplopia. Two
      patients with posterior fractures showed persistent diplopia, which was well
      managed by prisms. CONCLUSION: Endoscopic repair of the orbital floor blowout
      fracture using an endonasal approach appears to be a safe and effective technique
      for the treatment of diplopia.

PMID- 9932590
TI  - Better quality of life when nasal breathing of snoring men is improved at night.
AB  - OBJECTIVE: To evaluate whether improved nasal breathing changes the quality of
      life in snoring men and improves the female sleeping partners' well-being in the
      morning. DESIGN: During 1 month, 42 heavily snoring men slept with a nostril
      dilator. Before and after 1 month, the snorers rated their daytime tiredness and
      completed the Nottingham Health Profile questionnaire. Female sleeping partners
      rated the snoring, the quality of their sleep, and their sense of well-being in
      the morning. A population sample was used for comparison. SETTING: The Central
      Hospital, Skovde, Sweden. RESULTS: The snorers' quality of life before the study
      was significantly worse (P<.001) than that of the comparison population and
      improved significantly (P = .001). The men were significantly (P<.001) less tired
      during the day when their nasal airflow was increased. Female sleeping partners
      had significantly (P = .005) better sleep and an improved sense of well-being in
      the morning during the test period. Both were correlated with a significant
      reduction in the snoring (P<.001). CONCLUSIONS: When nasal breathing of snoring
      men was improved at night, their quality of life was significantly improved. The
      female sleeping partners had a reduction in sleep disturbance that correlated
      well with an improvement in their own sleep and feelings of well-being in the
      morning.

PMID- 9932592
TI  - Fungal mastoiditis in immunocompromised children.
AB  - The immunocompromised host is subject to a variety of opportunistic infections.
      Mycotic infections, including invasive fungal sinusitis, are a dreaded
      complication in immune deficient children. Fungal mastoiditis has rarely been
      described in this population. Our experience with 2 cases of fungal mastoiditis
      in immunocompromised children is reviewed. Case histories describing aggressive
      medical management with and without surgical intervention and a review of the
      literature are presented.

PMID- 9932591
TI  - Volume-length impact of lateral jaw resections on complication rates.
AB  - OBJECTIVE: To study the relationship between soft tissue volume loss and bone
      resection length following lateral segmental mandibulectomy with plate
      reconstruction and complication rates. DESIGN: Retrospective case review of 31
      patients (1989-1996), with average follow-up of 37.2 months, who were treated by
      lateral composite resection for oral cavity and/or oropharyngeal malignancy with
      primary reconstruction by defect-bridging plates. SETTING: Academic tertiary care
      referral center. INTERVENTIONS: Thirty patients had stainless steel and 1 patient
      a vitallium reconstruction plate to restore mandibular continuity. Soft tissue
      defects were repaired with pectoralis myocutaneous flaps (n = 25), skin grafts (n
      = 4), a radial forearm free flap (n = 1), or primary closure (n = 1). All
      patients received preoperative (n = 6) or postoperative (n = 25) radiation
      therapy. MAIN OUTCOME MEASURES: Overall and hardware-related complications.
      RESULTS: All 31 initial soft tissue repairs were successful. Subsequent
      complications occurred in 14 patients (45%), which included plate exposure (29%),
      loosened screws requiring hardware removal (29%), fistula (14%), local wound
      infection (14%), osteomyelitis (7%), and plate fracture (7%). Average time to
      complication was 7.7 months. Complication rates were 81% for bone defects greater
      than 5.0 cm, and 7% for those less than 5.0 cm. Bivariate analysis indicated bone
      resection lengths greater than 5.0 cm to be a significant predictor of both
      hardware-related (P = .02) and overall complications (P = .005), whereas soft
      tissue volume resections greater than 240 cm3 were found only to be marginally
      significant (P = .04) for overall complications. CONCLUSION: Extirpative losses
      involving more than 5 cm of bone, or tissue volume greater than 240 cm3, are
      associated with unacceptably high complication rates when reconstructed with
      solid screw stainless steel plates and this warrants consideration of alternative
      techniques for long-term stability.

PMID- 9932594
TI  - Impairment of T-cell activation in head and neck cancer in situ and in vitro:
      strategies for an immune restoration.
AB  - BACKGROUND: The rationale for the study was based on the hypothesis that
      decreased or absent expression on tumor cells of adhesion molecules, the class I
      or class II major histocompatibility complex (MHC) molecules, or costimulatory
      molecules might be responsible, in part, for the poor ability of squamous cell
      carcinoma of the head and neck (SCCHN) to induce generation of antitumor effector
      cells in vitro and in vivo. OBJECTIVE: To investigate expression of intercellular
      adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-3 (LFA-3)
      and distribution of the costimulatory molecules, B7.1, B7.2, and CD40, and of
      class I and class II MHC molecules on SCCHN cells in situ and on SCCHN cell
      lines. SETTING: University medical centers. DESIGN: Expression of ICAM-1, LFA-3,
      MHC molecules, B7.1, B7.2, and CD40 was evaluated in human SCCHN biopsy specimens
      by immunohistochemistry and on SCCHN cell lines by flow cytometry. To confirm our
      hypothesis that impaired T-cell activation observed in patients with SCCHN is
      caused by the absence of costimulatory B7 molecules, a B7-negative SCCHN cell
      line was transduced with the B7.1 gene, using a retroviral vector, and tested in
      mixed lymphocyte tumor cocultures. RESULTS: In contrast to abundant expression of
      ICAM-1, LFA-3, class I MHC molecules, and CD40, the absence of B7.1, B7.2, and
      class II MHC molecules on tumor cells was observed in situ and in vitro.
      Lymphocytes and antigen-presenting cells in inflammatory infiltrates surrounding
      tumor cell clusters expressed both costimulatory and adhesion molecules. The
      SCCHN lines negative for B7.1 and class II MHC antigens failed to induce
      proliferation of T cells in mixed lymphocyte tumor cocultures. However, when
      these cell lines were transduced with the B7.1 gene, their ability to induce T
      cell proliferation in mixed lymphocyte tumor cocultures was restored.
      CONCLUSIONS: The absence of B7 protein or class II MHC antigen expression on
      human SCCHN cells is responsible for the failure of these tumors to induce
      proliferation of T cells in vitro. Transduction of the B7.1 gene into SCCHN
      restores the ability of the tumor to induce T-cell proliferation in vitro.

PMID- 9932593
TI  - Transforming growth factor beta receptors and p27kip in thyroid carcinoma.
AB  - OBJECTIVE: To investigate the role of cell cycle regulators in the pathogenesis
      of papillary carcinoma of the thyroid. DESIGN: Resistance to transforming growth
      factor beta-mediated inhibition is a well-known pathogenic mechanism in
      epithelial neoplasias. In a retrospective study, the expression of transforming
      growth factor beta receptors types I and II, cyclin D1, and the cyclin-dependent
      inhibitor p27kip, was analyzed by immunohistochemistry. Results were interpreted
      in the context of clinicopathological data. Patient follow-up ranged from 1 to 18
      years, with a mean of 4 years. MATERIALS: Twenty conventional primary papillary
      carcinomas and their metastases were selected according to current pathologic
      criteria. Nonconventional papillary carcinomas (eg, tall-cell, columnar) were
      excluded from the analysis. RESULTS: Cyclin D1 was expressed more intensely in
      the tumor than in adjacent nonneoplastic parenchyma. Within a given tumor,
      however, there was significant heterogeneity in expression intensity and
      percentage of positive cells, particularly in metastases. Type I receptors were
      strongly expressed in 90% of tumors, while 80% of the tumors revealed low to no
      expression of type II receptors. In 10% of tumors, type I receptors were absent
      and type II receptors expressed. Simultaneous absence of both receptors was not
      observed. While p27kip was strongly expressed in nonneoplastic thyroid, it was
      not detected in any of the primary tumors or their metastases. CONCLUSIONS: The
      results strongly suggest that functional abnormalities in type II receptors
      result in increased levels of cyclin D1 and down-regulation of p27kip. This would
      maintain cells in a proliferative state and would promote tumor progression.

PMID- 9932595
TI  - Extended endoscopic frontal sinus surgery to interrupted nasofrontal
      communication caused by scarring of the anterior ethmoid: long-term results.
AB  - OBJECTIVE: To examine the long-term results of extended endoscopic frontal sinus
      surgery, including removal of the floor of the frontal sinus (Draf type II
      procedure) and the median drainage operation (Draf type III procedure or modified
      Lothrop procedure), for obstructive frontal sinusitis caused by postoperative
      scar formation, with the emphasis on the long-term success of the median drainage
      procedure. DESIGN: Retrospective review of 22 consecutive cases of extended
      endonasal frontal sinus surgery in patients with obstructive frontal sinusitis
      caused by postoperative scarring. SETTING: The procedures were performed at a
      private surgicenter in Japan. PATIENTS: Twenty-two patients (15 males and 7
      females) ranging in age from 14 to 61 years. All patients had scar formation in
      the anterior ethmoid, either with or without middle turbinate lateralization or
      ethmoiditis. Three patients underwent Draf type II procedure followed by Draf
      type III procedure because of surgical failure of the type II procedure. MAIN
      OUTCOME MEASURES: Restoration of communication to the frontal sinus was evaluated
      by computed tomography. All patients were examined at least 12 months after
      surgery or stent removal. RESULTS: Of the 16 patients who underwent the type III
      procedure, in 14 (88%) the patency of the opening to the frontal sinus and an
      aerated sinus were confirmed. Of 12 sides in 9 patients who underwent Draf type
      III procedure, 5 sides (42%) were also confirmed as "cured." CONCLUSIONS: The
      median drainage operation (Draf type III procedure) on the frontal sinus showed
      excellent long-term results compared with the type II procedure. Extended
      endoscopic frontal sinus surgery, particularly the median drainage procedure, is
      useful in the functional treatment of obstructive frontal sinusitis caused by
      postoperative scarring.

PMID- 9932597
TI  - Imaging quiz case 1. Displaced stapes prosthesis; otosclerosis.

PMID- 9932596
TI  - Effects of mucokinetic drugs on rheological properties of reconstituted human
      nasal mucus.
AB  - OBJECTIVE: To investigate the effects of mucokinetic drugs on the rheological
      properties of human nasal mucus in patients with chronic sinusitis. DESIGN: We
      reconstituted human nasal mucus obtained from 74 patients with chronic sinusitis
      and determined the effects of 4 mucokinetic drugs, including acetylcysteine,
      deoxynuclease I, 2% sodium bicarbonate, and a combination product containing
      tyloxapol (Alevaire), on rheological properties of reconstituted human nasal
      mucus (RHNM). We used 5% RHNM dissolved in phosphate-buffered solution as the
      optimal buffer and concentration of RHNM for the study because it showed a
      viscoelastic response similar to that of freshly collected nasal mucus from
      patients with chronic sinusitis. METHODS: Four experiments were performed to
      determine the influence of each drug on dynamic viscosity and elasticity of 5%
      RHNM. Distilled water was used as a control. RESULTS: Acetylcysteine and
      deoxynuclease I significantly decreased both dynamic viscosity and elastic
      modulus, while distilled water had no effect on rheological properties of 5% RHNM
      in vitro. Alevaire significantly reduced both dynamic viscosity and elastic
      modulus. Sodium bicarbonate significantly reduced elastic modulus but not dynamic
      viscosity. Reduction of elastic modulus by Alevaire was significantly greater
      than that by sodium bicarbonate, while there was no difference in reduction of
      dynamic viscosity between them. CONCLUSION: Our results indicate that RHNM may be
      useful for studying the topical effects of various drugs on nasal mucus from
      patients with chronic sinusitis.

PMID- 9932598
TI  - Imaging quiz case 2. Intralabyrinthine schwannoma.

PMID- 9932599
TI  - Value of neck dissection in the treatment of patients with intermediate-thickness
      cutaneous malignant melanoma of the head and neck.

PMID- 9932601
TI  - Considerations in the surgical treatment of malignant melanoma.

PMID- 9932600
TI  - Experience and clinical judgment required in the treatment of malignant melanoma.

PMID- 9932602
TI  - The European Consensus Development Conference on Neonatal Hearing Screening
      (Milan, May 15-16, 1998)

PMID- 9932603
TI  - The Shaw hemostatic scalpel in parotid surgery.

PMID- 9932604
TI  - Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast
      carcinomas: clinico-pathological correlations.
AB  - The purpose of this study was to investigate the association among matrix
      metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin)
      mRNAs expressed in primary breast carcinomas and standard prognostic parameters
      and clinical outcome. mRNA levels were determined by Northern analysis in samples
      of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of
      uninvolved adjacent breast tissue. Proteases were expressed by the majority of
      the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin
      mRNAs were more often expressed at high levels in carcinomatous than in normal
      breast tissues. Differences in the distribution of gelatinase B mRNA were not
      found. However, paired normal tissues generally produced weaker signals when
      compared to matched tumor samples. Univariate analysis showed no significant
      association of gelatinase A and matrilysin mRNAs with the classical prognostic
      markers (age, menopausal status, stage, size, nodal status, vascular infiltrate,
      necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was
      more frequently found in tumors of post-menopausal women (P < 0.022). Elevated
      expression of gel B mRNA was associated with the presence of vascular infiltrate
      (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely
      correlated to the number of survivors (P < 0.021). Multivariate analysis
      including 68 patients for whom all information was available indicated that
      neither stromelysin correlated significantly with pathological, clinical or
      biochemical features. High levels of gelatinase A and B mRNAs were inversely
      associated with the number of survivors. Our findings suggest that measurements
      of gelatinase A and B mRNAs expression in breast carcinoma may help to identify
      patients with an aggressive form of the disease.

PMID- 9932605
TI  - Low density lipoproteins and Lovastatin modulate the organ-specific
      transendothelial migration of primary and metastatic human colon adenocarcinoma
      cell lines in vitro.
AB  - Tumor cell arrest and tumor migration are two of the critical steps in the
      metastatic cascade. We hypothesized that these steps may be facilitated by the
      low density lipoprotein (LDL)-induced activation of microvessel endothelial cells
      (MVEC). The purpose of our study was to investigate the biological effects of an
      LDL-enriched milieu and the effects of the anticholesterol drug Lovastatin on
      metastatic behavior. The SW480 and SW620 are primary and metastatic human colonic
      adenocarcinoma cell lines derived from the same patient. We investigated the
      effect of LDL on adhesion and migration of the two tumor cell lines across human
      brain, lung, liver and dermal endothelial monolayers. Adhesion and migration
      assays were done before and after pretreatment of the MVEC or tumor cells with
      LDL (100 microg/ml) for 24 h. Although metastatic SW620 cells were more adherent
      to MVEC compared with primary SW480 cells, LDL pretreatment of SW480 and SW620
      cells did not affect tumor cell adhesion to MVEC. In contrast, tumor cell
      migration was significantly increased across endothelial monolayers when MVEC
      were pretreated with LDL. Transendothelial cell migration was not significantly
      affected by pretreatment of the tumor cells with LDL. Lovastatin is an inhibitor
      of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. It
      has been shown to have anti-tumor activity in vitro. We investigated the effect
      of Lovastatin on tumor cell kinetics and tumor cell migration across MVEC. Growth
      curves and migration assays were done before and after pretreatment of the tumor
      cells with Lovastatin (30 microg/ml). Migration assays were also done after
      treatment of unstimulated or LDL-stimulated MVEC (100 microg/ml) for 24 h with
      Lovastatin. Lovastatin inhibited the in vitro growth of the metastatic SW620 cell
      line to a greater extent than the invasive SW480E cell line. On the other hand,
      pretreatment of tumor cells with Lovastatin (30 microg/ml) did not suppress
      transendothelial tumor cell migration of tumor cells. Finally, Lovastatin given
      to mice effectively suppressed the number of MCA-26 tumor colonies in the liver
      of Balb/c mice compared with untreated mice.

PMID- 9932606
TI  - Association between nm23-H1 expression, proliferation and apoptosis in non-small
      cell lung carcinomas.
AB  - Twelve non-small cell lung carcinomas and adjacent normal lung tissues were
      examined for mutations of the nm23-H1 gene by using SSCP analysis and for an
      expression of the nm23-H1 protein by immunohistochemistry. No mutations could be
      found in either the carcinomas or in the adjacent normal tissues. In contrast,
      six of 12 carcinomas showed protein expression while only one adjacent normal
      lung tissue yielded a positive staining result. Therefore, the expression of nm23
      H1 protein was analysed in a larger group of non-small cell lung carcinomas (n =
      185) to determine whether or not the expression of nm23 protein may be of
      prognostic relevance. Only a weak relationship between nm23-H1 expression and
      lymph node involvement was observed. However, a significant correlation between
      proliferation and nm23-H1 expression was detected. Additionally, a direct
      correlation between apoptosis and nm23-H1 expression or between myc and nm23-H1
      expression was found. Finally, non-small cell lung carcinomas that expressed nm23
      H1 protein were more frequently sensitive to doxorubicin than carcinomas that did
      not express this protein.

PMID- 9932607
TI  - Detection of differentially expressed gelatinase A in metastatic and non
      metastatic subpopulations of tumor cells by target RNA arbitrarily primed
      polymerase chain reaction (TRAP-PCR).
AB  - We have developed a novel procedure called Targeted RNA AP-PCR (TRAP-PCR) to
      quantitatively measure specific mRNA expression. The target mRNA is reverse
      transcribed using a specific primer and PCR is performed under low stringency
      conditions to generate a rich fingerprint-type band pattern. In this situation
      multiple sequences are coamplified with the targeted sequence. The amplification
      is carried out in a competitive fashion and is, in consequence, quantitative. We
      have applied this technique to determine Gelatinase A (Gel A) mRNA expression in
      the MXT mouse mammary carcinoma system. TRAP-PCR analysis using primers for Gel A
      produced a reproducible fingerprint including one major band whose identity was
      confirmed to be Gel A cDNA. Highly metastatic MXT subclones show an increased Gel
      A expression. Results were confirmed by Northern blot and protein activity
      (gelatin zymography). TRAP-PCR is a simple, sensitive and specific technique to
      comparatively quantify mRNA expression and requires less template than
      conventional methods.

PMID- 9932608
TI  - Stimulation of cellular growth and adhesion to fibronectin and vitronectin in
      culture and tumorigenicity in nude mice by overexpression of trypsinogen in human
      gastric cancer cells.
AB  - It has previously been reported that the trypsinogen gene is expressed in various
      human cancers. To investigate the possible role of trypsin in tumor malignancy,
      trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN
      1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth
      and adhesion to fibronectin and vitronectin when the trypsinogen activator
      enterokinase was added into the culture. Enterokinase treatment of the
      conditioned medium of the MKN-1 transfectants partially converted the proforms of
      gelatinases B and A to their apparent active forms. When the MKN-1 transfectants
      expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the
      mice frequently produced tumors in the colon, spleen and liver. However, the mice
      implanted with control MKN-1 cells produced no tumors. These results strongly
      suggest that tumor-derived trypsin contributes to the disseminated growth of some
      types of cancer cells including gastric cancer.

PMID- 9932609
TI  - Antimetastatic vaccination against Lewis lung carcinoma with autologous tumor
      cells modified to express murine interleukin 12.
AB  - Interleukin 12 (IL-12) is a disulfide-linked heterodimer molecule produced
      predominantly by professional antigen presenting cells. It promotes the induction
      of sundry biological effects with significant relevance to antitumor immunity,
      such as enhancing a T(H)1 helper response, an in vivo antiangiogenic effect,
      induction of adhesion molecules that assist in lymphocyte homing to sites of
      tumor growth, and a direct stimulatory effect on both T-cells and NK cells. We
      tested the efficacy of an antimetastatic vaccine composed of autologous murine
      D122 cells transfected with both subunits of IL-12 cDNA to express biologically
      active IL-12 molecule. Expression of IL-12 by D122 cells significantly reduced
      their tumorigenicity and metastatic potential in immunocompetent syngeneic hosts.
      Furthermore, vaccination of mice with 2 x 10(6) irradiated IL-12-transfected D122
      cells engendered a protective CTL response which rejected a subsequent challenge
      with parental D122 cells and eradicated lung micrometastasis in animals whose
      primary tumors have been surgically removed. The antitumor effects of IL-12 were
      mediated primarily by its ability to induce gammaIFN expression in vivo. CD8+ T
      cells as well as NK cells were crucial in the execution of the antitumor effects
      of IL-12. These results suggest that autologous tumor cells expressing IL-12 by
      gene transfer are a potent antitumor vaccine able to induce a systemic immune
      response against poorly immunogenic and spontaneously metastatic tumors.

PMID- 9932610
TI  - 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) inhibits the
      intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of
      tumor-bearing animals.
AB  - We examined the in vivo anti-tumor activity of the benzoic acid derivative, TAC
      101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), for intrahepatic spread
      of JHH-7 human hepatocellular carcinoma (HCC) cells and its mechanism of action.
      Oral administration of TAC-101 markedly inhibited liver tumor of JHH-7 cells and
      prolonged the life-span of tumor-bearing mice without affecting the body weight.
      The life-prolonging effect of TAC-101 was more effective than that of other anti
      cancer agents including CDDP, 5-FU, and CPT-11 (T/C (%) of life-span; 181 to 219,
      128, 133, and 142%, respectively). In vitro, TAC-101 at the concentration of more
      than 10 microM showed direct cytotoxicity against JHH-7 cells caused by induction
      of apoptosis. Hepatocyte growth factor (HGF) enhanced the invasive ability of JHH
      7 cells without affecting the cell viability. Non-cytotoxic concentrations of TAC
      101 inhibited the JHH-7 invasion induced by HGF and down-regulated the expression
      of c-MET protein in a concentration-dependent manner. In summary, these results
      suggest that TAC-101 would be useful for a new class of therapeutic agents and
      that it may improve the prognosis of patients with liver-tumors including
      metastasizing tumor and HCC.

PMID- 9932611
TI  - Growth and dissemination of a newly-established murine B-cell lymphoma cell line
      is inhibited by multimeric YIGSR peptide.
AB  - B-cell lymphoma frequently shows simultaneous dissemination to multiple organs.
      It also occasionally involves bone and causes osteolytic lesions. To study the
      mechanisms responsible for this capacity of lymphoma cells to grow in different
      tissue microenvironments and search for effective therapeutic interventions for
      this hematological malignancy, we established a new murine B-cell lymphoma cell
      line named MH-95. The tumor disseminated to multiple organs including the lung,
      liver, kidney, spleen and lymph nodes within 2 weeks after subcutaneous
      inoculation in nude mice. In addition, the tumor also grew in bone and caused
      osteoclastic osteolytic lesions. Thus, this tumor model mimics the behavior in
      many ways of B-cell lymphoma in humans. We studied the role of laminin, a major
      component of the basement membrane, in this model, since although it has been
      implicated in solid tumor metastasis, little is known about the involvement of
      laminin in the growth of B-cell lymphoma in bone and other organs.
      Immunohistochemical examination showed strong laminin expression in the stroma of
      the primary subcutaneous tumor and tumors in the bone and other organs. Systemic
      administration of the antagonistic laminin peptide YIGSR decreased primary tumor
      growth and tumor cell deposit in the bone, liver and kidney. In addition, the
      peptide also decreased apparent neovascularization in the tumor, suggesting that
      the peptide suppressed angiogenesis presumably due to inhibition of laminin
      binding to its receptors. These results demonstrate that the MH-95 B-cell
      lymphoma cells express laminin and suggest that laminin plays a critical role in
      the growth and simultaneous dissemination of tumor cells to multiple organs,
      similar to what has been described in solid tumors. The results also suggest that
      suppression of angiogenesis through interfering with laminin actions may be a
      useful adjuvant therapy for B-cell lymphoma.

PMID- 9932612
TI  - The host environment promotes the development of primary and metastatic squamous
      cell carcinomas that constitutively express proinflammatory cytokines IL-1alpha,
      IL-6, GM-CSF, and KC.
AB  - Human and murine squamous cell carcinomas (SCC) have been reported to produce
      proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and IL-8 or KC. Production of
      individual members of the proinflammatory cytokine family has been associated
      with increased tumor growth or metastasis in a variety of neoplasms. In this
      study, we determined whether the expression of these cytokines occurs as a result
      of the events of cellular transformation or culture, or is promoted by
      interaction of neoplastic cells with factors or cells in the host environment. We
      compared the expression of proinflammatory cytokines following the spontaneous
      transformation of murine keratinocytes in vitro, and following the formation of
      tumors and metastases from these transformed keratinocytes in syngeneic
      recipients in vivo. Using sensitive ELISA assays, we found that cultures of the
      in vitro transformed Balb/c SCC line Pam 212 do not produce elevated levels of
      proinflammatory cytokines IL-1alpha, IL-6, GM-CSF and KC, indicating that
      transformation or culture alone is insufficient to account for the level of
      cytokine expression detected in patient and experimental tumors. In contrast, Pam
      reisolates from primary and metastatic tumors were obtained which constitutively
      produce markedly elevated levels of cytokines IL-1alpha, IL-6, KC and GM-CSF. The
      increase in the expression of these cytokines by SCC in vivo occurred independent
      of T and B lymphocyte-mediated immunity, since increases in expression of the
      cytokines was observed in lines reisolated from immunodeficient athymic nude and
      SCID Balb/c congenic mice. The increased expression of cytokines appeared to
      result from additional events in vivo, rather than due to selection of a pre
      existing cytokine-producing subpopulation, since clones of the parental cell line
      expressed lower cytokine levels than cloned reisolates, and clones of the non
      secreting parental cell line that formed tumors in vivo secreted elevated levels
      of cytokines following reisolation. We conclude that the development of SCC that
      express proinflammatory cytokines is promoted by tumor-host interaction(s) that
      are independent of specific T and B cell immunity.

PMID- 9932614
TI  - Stroke risk factors and stroke prevention.
AB  - Stroke is the third leading cause of death and the leading cause of chronic
      disability in the United States. In the past several decades, case series, case
      control studies, and prospective cohort studies have successfully identified
      nonmodifiable risk markers for stroke, such as age, gender, race, ethnicity,
      heredity and several well-established modifiable risk factors for ischemic
      stroke. Hypertension, atrial fibrillation, other cardiac diseases,
      hyperlipidemia, diabetes, cigarette smoking, physical inactivity, carotid
      stenosis, and transient ischemic attack (TIA) are all potentially treatable
      conditions that predispose to stroke. Research on other putative stroke risk
      factors-including antiphospholipid antibodies, elevated homocysteine, alcohol,
      inflammation, and infection-is ongoing. Controlled trials have shown that stroke
      risk can be reduced by blood-pressure control, lipid-lowering agents, surgery for
      carotid stenosis, warfarin for atrial fibrillation, and antiplatelet agents. It
      is hoped that an improved understanding of stroke risk factors will reduce the
      future burden of stroke.

PMID- 9932615
TI  - Antiplatelet agents and stroke prevention.
AB  - Aspirin (acetylsalicylic acid [ASA]) from 75 to 1,300 mg/day is an effective
      agent in the secondary prevention of stroke. Although no properly designed study
      has been performed, circumstantial evidence suggests that the favorable effect of
      ASA for stroke may be enhanced by higher doses. Ticlopidine is more effective
      than 1,300 mg/day of ASA, and clopidogrel is at least as effective as 325 mg of
      ASA a day; but, for various reasons, ASA at higher doses is still first choice by
      many. Three studies have shown no benefit of adding dipyridamole to ASA. A fourth
      did, but, in addition to other problems, the results are no better than those
      obtained by higher doses of ASA alone. ASA is an effective alternate to warfarin
      for patients with atrial fibrillation and contraindications to warfarin. Until a
      proper study has been performed, ASA is not recommended for the prevention of
      stroke in a low-risk asymptomatic elderly population.

PMID- 9932613
TI  - Neo-angiogenesis in locally advanced squamous cell head and neck cancer
      correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein
      accumulation.
AB  - Thymidine phosphorylase (Th.P) is an angiogenic factor shown to induce
      endothelial cell migration and proliferation. On the other hand, loss of wild
      type p53 function leads to down-regulation of thrombospondin-1, an inhibitor of
      angiogenesis. In this immunohistochemical study we investigated the intratumoural
      angiogenesis and thymidine phosphorylase (Th.P) expression in paraffin-embedded
      bioptical material from 104 locally advanced squamous cell head and neck cancers.
      The nuclear accumulation of mutant p53 protein and the cytoplasmic expression of
      bcl-2 protein was also assessed. High vascular grade was observed in 56% and high
      Th.P tumour cell reactivity in 48% of cases. High microvessel score was
      associated with an increased percentage of cancer cells expressing thymidine
      phosphorylase (P = 0.001). Increased p53 nuclear accumulation also correlated
      with high vascular grade (P = 0.001). High histological grade and absence of bcl
      2 overexpression were associated with lymph node involvement (P = 0.002 and P =
      0.02 respectively). No correlation of clinically detected lymphadenopathy with
      angiogenesis and p53 was observed. We conclude that intense neo-angiogenesis in
      locally advanced squamous cell head neck cancer is a frequent event, which is
      associated with nuclear p53 accumulation and thymidine phosphorylase
      overexpression.

PMID- 9932616
TI  - Primary and secondary stroke prevention in atrial fibrillation.
AB  - Atrial fibrillation, with a prevalence of 6% in those over 65 years, is
      responsible for 75-100 x 10(3) strokes each year in the United States. These
      strokes are more severe and have less favorable long-term prognosis than strokes
      due to other mechanisms. Modern trials show that warfarin reduces stroke rate by
      about 70% and aspirin by about 20%. Although average annual stroke rate among
      atrial fibrillation patients is about 4-5%, considerable risk heterogeneity
      exists. The goal of risk stratification is to differentiate patients with risk
      high enough to justify warfarin from those whose risk is so low that they are
      better off on aspirin or even no antithrombotic therapy. Ideal antithrombotic
      therapy is individualized, balancing risks of thromboembolism versus bleeding on
      antithrombotic therapy, and considering patient preferences. Although the science
      has advanced significantly in the past decade, application has lagged behind.
      Much benefit will potentially accrue from broad education efforts.

PMID- 9932617
TI  - Anticoagulant and defibrinogenating agents in acute ischemic stroke and cerebral
      venous thrombosis.
AB  - Anticoagulants have been used in patients with acute ischemic stroke to limit
      infarct volume and to prevent reinfarction and thrombotic complications like deep
      venous thrombosis. Three important randomized trials of anticoagulants have been
      reported recently. One trial showed that nadroparin reduced the percentage of
      patients with poor outcome at 6 months. One unblinded trial of subcutaneous
      unfractionated heparin showed that heparin reduced the rate of early recurrent
      stroke, but this benefit was offset by an increase in hemorrhages. A trial of the
      heparinoid ORG 10172 showed no efficacy overall at 3 months, although there was
      an increase in patients with very favorable outcomes at 7 days. The
      defibrinogenating agent ancrod has shown promise in a series of small clinical
      trials, but efficacy has not been established. There are no reliable data on the
      use of antithrombotic agents to prevent reocclusion after thrombolytic therapy.
      Anticoagulants are generally recommended in patients with cerebral venous
      thrombosis, but the recommendation is supported by only one small and
      methodologically limited trial.

PMID- 9932618
TI  - Recanalization therapies for acute ischemic stroke.
AB  - Angiographic studies performed within 6 hours of stroke onset have demonstrated
      that 75-80% of patients with an acute ischemic stroke have an angiographically
      visible occlusion of an extracranial and/or intracranial artery that is the cause
      of the ischemic stroke. The NINDS t-PA Stroke Study demonstrated that
      recanalization of occluded brain arteries can successfully salvage ischemic brain
      if intravenous tissue plasminogen activator (t-PA) is initiated within 3 hours of
      stroke onset. The effectiveness and safety of intravenous t-PA beyond 3 hours has
      yet to be shown. Large clots in the internal carotid artery, vertebral or basilar
      artery, or middle cerebral artery trunk are infrequently lysed by intravenous t
      PA during the first hour of treatment. Intraarterial delivery of a thrombolytic
      agent appears to lyse clots in cerebral arteries more effectively than
      intravenous t-PA. However, a head-to-head comparison of full-dose intravenous t
      PA and intraarterial therapy has yet to be done, and recanalization rates
      reported in the intraarterial studies are at longer times after the start of
      therapy than the rates of recanalization reported in intravenous t-PA studies.
      Intraarterial delivery of thrombolytic therapy takes longer than intravenous
      delivery, and even intraarterial delivery takes 2 hours on average to partially
      or completely lyse 75% of clots. Intraarterial delivery of a thrombolytic agent
      has yet to be proven effective and safe in improving long-term outcome of
      ischemic stroke patients. The approach of combining intravenous and intraarterial
      delivery of t-PA or other pharmacologic agents is an attractive option that
      deserves further study. Mechanical lysis of clots, in combination with
      pharmacologic therapies, is a more effective way to recanalize coronary arteries
      and salvage heart muscle than intravenous thrombolytic therapy alone. This
      approach is likely to be effective in ischemic stroke as well. What is needed is
      advances in catheter technology that meet the special requirements of clot lysis
      in cerebral vessels. Whether neuroprotective agents can extend the therapeutic
      window for effective clot lysis and recanalization remains to be seen.
      Thrombolytic therapy and other pharmacologic treatments of clot in cerebral
      vessels will likely remain a two-edged sword. Pharmacologic therapies that
      increase the likelihood of clot lysis and recanalization, such as thrombolytic
      agents, the platelet GIIbIIIa receptor blockers, defibrinogenating agents, and
      even the newer more potent thrombolytic agents, also concomitantly increase the
      risk of bleeding into the brain. What we will be searching for in the coming
      decade is the correct mechanical strategy, dose of a given pharmacologic agent,
      or combination of agents that maximizes recanalization and minimizes the risk of
      intracerebral hemorrhage.

PMID- 9932620
TI  - Carotid endarterectomy.
AB  - Carotid endarterectomy is an established surgical procedure to prevent stroke.
      The indications, preoperative evaluation, surgical timing, technical details,
      complications, and special circumstances for the use of this operation are
      reviewed. Future developments in the surgical reconstruction of the extracranial
      carotid artery are also discussed.

PMID- 9932619
TI  - Neuroprotective therapy.
AB  - The concept of neuroprotection relies on the principle that delayed neuronal
      injury occurs after ischemia. The phenomenon of the "ischemic cascade" has been
      described, and each step along this cascade provides a target for therapeutic
      intervention. In animal models of global and focal cerebral ischemia, numerous
      preclinical studies have demonstrated various agents to be neuroprotective at
      different steps along this cascade. A wide variety of drugs has also been studied
      in humans. Ten classes of neuroprotective agents have reached phase III efficacy
      trials but have shown mixed results. They include calcium channel antagonists,
      NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger
      tirilizad, anti-intercellular adhesion molecule-1 (ICAM-1) antibody, GM-1
      ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and
      piracetam. In the future, clinicians may have an armamentarium of treatments for
      acute ischemic stroke at their disposal, with a combination of agents directed at
      different sites in the ischemic cascade being the ultimate goal.

PMID- 9932621
TI  - The role of carotid angioplasty and stenting.
AB  - The prevention of stroke in patients with carotid pathology has been
      traditionally carried out with either medications that prevent clot formation
      (i.e., warfarin or antiplatelet agents) or revascularization of stenotic segments
      of the artery by surgical means (i.e., carotid endarterectomy). Recently, the use
      of percutaneous endovascular techniques, to treat lesions of the carotid artery
      has become increasingly popular. The most important techniques being used for
      this purpose are balloon angioplasty and stenting. Although still under intense
      investigation, it is already clear that endovascular therapy of the carotid
      artery is effective in the correction of lesions not readily accessible by
      surgery, those due to recurrent stenosis after endarterectomy, those not of an
      atherosclerotic nature, and those with unusually high surgical morbidity and
      mortality. The role of endovascular therapy in the treatment of type A lesions,
      which are perfect for endarterectomy, awaits the completion of prospective
      randomized trials. However, care must be exercised in the planning of these
      trials to allow a fair testing of the endovascular procedures.

PMID- 9932622
TI  - Medical and surgical management of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage accounts for about 10% of all strokes. The diagnosis of
      this stroke subtype has been revolutionized by the use the computed tomography
      scanner. Therapeutic intervention in the form of medical and surgical management
      is reviewed. The critical management issues center on identifying the etiology of
      hemorrhage, controlling blood pressure, and controlling intracranial pressure.

PMID- 9932623
TI  - Treatment of aneurysmal subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage is a formidable and common health care problem. Early
      diagnosis and management are crucial to reduce the morbidity form this complex
      and multifaceted disease. Open surgery and endovascular techniques both aim at
      eliminating the source of hemorrhage. The choice of therapy can be made
      rationally based on an understanding of the merits, risks, and limitations of
      each therapy. The care of pregnant patients with subarachnoid hemorrhage and
      patients who harbor both aneurysms and AVMs can be approached rationally with an
      understanding of the complex pathophysiology behind these clinical scenarios.
      Familiarity with the signs of mild SAH, and advances in familial screening,
      noninvasive imaging, and therapies for vasospasm will continue to lessen the toll
      of this dramatic illness on the public well-being.

PMID- 9932624
TI  - American history 101: presidents, vice presidents, and paralytic illness.
AB  - Neurological disease has had a profound effect on history as with the fatal
      stroke of Franklin D. Roosevelt. Roosevelt and two of his vice presidents, Harry
      Truman, and Henry Wallace also suffered from acquired paralytic disorders. The
      sum total of the neurological problems of these three statesmen had a significant
      effect on their careers, and the course of history.

PMID- 9932625
TI  - Problems in the pharmacological evaluation of paroxysmal atrial fibrillation.

PMID- 9932626
TI  - Current medical approach to thyroid stimulating hormone-secreting pituitary
      adenomas.

PMID- 9932627
TI  - Allogeneic peripheral blood stem cell transplantation as an alternative to
      allogeneic bone marrow transplantation.

PMID- 9932628
TI  - Pontiac fever: non-pneumonic form of legionellosis.

PMID- 9932629
TI  - Problems in pharmacological evaluation of patients with paroxysmal atrial
      fibrillation: clinical analysis of more than 100 consecutive patients.
AB  - To address the problems of pharmacological evaluation in paroxysmal atrial
      fibrillation (PAf), we interviewed 108 consecutive patients with documented PAf
      regarding symptoms, frequency and trigger factors of PAf and analyzed the 24-hour
      ambulatory electrocardiographic monitoring (Holter monitoring) records in
      relation to symptoms. Twenty-nine patients were totally asymptomatic, while 79
      patients were symptomatic of which 49 patients had obvious trigger factors. PAf
      was documented by Holter monitoring in 22 of 79 symptomatic patients. On analysis
      of PAf-documented 25 Holter monitoring records, the patients checked event marks
      as PAf in only 20 of 155 PAf episodes. Six episodes of 26 event marks that
      patients thought to be PAf proved to be premature atrial or ventricular
      contractions. Nine patients in whom PAf persisted for more than 24 hours became
      asymptomatic. Patients suitable for pharmacological evaluation constituted about
      one-fifth of the PAf patients in our consecutive study. Even with the selection
      of these patients, pharmacological evaluation based on symptoms is difficult
      because disappearance of PAf may be associated with persistent atrial
      fibrillation.

PMID- 9932630
TI  - Acute effects of nasal continuous positive airway pressure on 24-hour blood
      pressure and catecholamines in patients with obstructive sleep apnea.
AB  - To assess the acute effects of nasal continuous positive airway pressure (CPAP)
      on the 24-hour blood pressure and the secretion of catecholamines in urine and
      plasma, we investigated the changes in the 24-hour blood pressure and urinary and
      plasma concentrations of epinephrine (E) and norepinephrine (NE) in 26 men with
      obstructive sleep apnea (OSA) with and without nasal CPAP. Nasal CPAP resulted in
      significant decreases in the daytime diastolic pressure (from 86 +/-16 mmHg to
      83+/-12 mmHg), the nighttime diastolic pressure (from 81+/-12 mmHg to 77+/-9
      mmHg) and the nighttime systolic pressures (from 125+/-15 mmHg to 120+/-10 mmHg).
      There was no significant difference between patients with and without CPAP in the
      daytime or nighttime urinary E level, but patients who received CPAP showed a
      significant decrease in daytime urinary NE level (from 156+/-112 microg/14h to
      119+/-101 microg/14h) and nighttime urinary NE level (from 143+/-91 microg/10h to
      112+/-65 microg/10h). The morning plasma level of NE also decreased (from 371+/
      181 pg/ml to 273 +/-148 pg/ml) in patients who received nasal CPAP (p<0.02), but
      the plasma level of E remained unchanged. There were no correlations between PSG
      parameters and the reductions in blood pressure and the catecholamine levels
      induced by nasal CPAP. These findings suggest that OSA contributes, at least in
      part, to the development of systemic hypertension by increasing sympathetic
      nervous activity.

PMID- 9932631
TI  - Changes in the incidence and etiological patterns of bacteremia associated with
      acute leukemia over a 25-year period.
AB  - During the 25-year period from 1972-1996, 360 episodes of bacteremia occurred in
      248 (45%) of a total of 548 patients with acute leukemia on our hematology ward,
      with the rate of occurrence remaining almost unchanged. Patients with acute
      nonlymphocytic leukemia, however, had a significant decrease in the incidence of
      bacteremia during the last 5-year period. Gram-negative bacilli decreased in
      relative frequency from 64% for the first 15-year period to 40% for the last 5
      year period, whereas gram-positive cocci increased from 24% to 51%. Escherichia
      coli and Enterobacter cloacae somewhat decreased in frequency, whereas coagulase
      negative staphylococci and streptococci had considerable increases. In contrast,
      Pseudomonas aeruginosa was isolated at a relatively constant frequency, forming
      one of the top two pathogens throughout the study period. Despite the shift
      toward gram-positive cocci, therefore, P. aeruginosa remains a key organism in
      considering the initial empiric antibiotic regimen and infection prevention
      during neutropenia.

PMID- 9932632
TI  - Spontaneous remission of hypertrophic lymphocytic gastritis associated with
      hypoproteinemia.
AB  - A 54-year-old woman came to our office because of pretibial edema. She had no
      gastrointestinal symptoms. Laboratory tests revealed severe hypoproteinemia.
      Upper gastrointestinal endoscopy demonstrated enlarged gastric folds and multiple
      aphthoid nodules on the body and the fornix of the stomach. The biopsy specimen
      revealed a large number of CD8 positive intraepithelial T-lymphocytes
      infiltrating the gastric mucosa. Both serum total protein and the gastric lesions
      improved eight months after her first visit without any therapy for peptic ulcer
      or eradication of Helicobacter pylori. The data suggest that spontaneous
      remission may occur in lymphocytic gastritis without any gastrointestinal
      symptoms.

PMID- 9932634
TI  - Thyrotropin secreting pituitary adenoma effectively treated with octreotide.
AB  - We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma,
      who was diagnosed based on the lack of inhibition of serum TSH despite an
      increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin
      releasing hormone, and a pituitary tumor as revealed by magnetic resonance
      imaging. The pituitary adenoma was, however, inoperable due to chronic
      respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d.
      resulted in inhibition of serum TSH and free T4 to euthyroid levels and
      considerable shrinkage of the pituitary tumor. These effects were continued over
      8 months after the start of octreotide therapy without any adverse effects. These
      findings add further evidence that octreotide is useful for treating inoperable
      TSH secreting pituitary adenoma.

PMID- 9932633
TI  - Primary cardiac angiosarcoma of the right atrium undiagnosed by transvenous
      endocardial tumor biopsy.
AB  - A 50-year-old man was admitted with acute pericarditis. Echocardiography
      demonstrated a large mass on the right atrial free wall along with a pericardial
      effusion. We performed transvenous biopsy of this mass under transesophageal
      echocardiographic guidance. Though the biotome obtained the mass, the
      pathological findings were of organized thrombus. Two weeks later, a new
      precordial mass appeared around the left third rib and was suspected to be a
      metastasis. Incisional biopsy of this mass gave the diagnosis of angiosarcoma.

PMID- 9932635
TI  - Lipoatrophy induced by recombinant human insulin injection.
AB  - A 79-year-old man had been treated with recombinant human insulin since the age
      of 77. He developed subcutaneous fat atrophy around the injection site 16 months
      after induction of insulin therapy. Skin biopsy of the atrophic site revealed
      inflammatory changes and adipocyte atrophy. Changing the type of insulin and
      injection site relieved the fat atrophy. Although insulin-induced lipoatrophy was
      a common complication before the development of human insulin, it is now rare.
      The immunological reaction to the insulin product, as in conventional impure
      insulin-induced lipoatrophy, seemed to be involved in the etiology of lipoatrophy
      in this case.

PMID- 9932636
TI  - Giant hepatic biloma following transcatheter oily chemoembolization in a patient
      with hepatic metastases from malignant pheochromocytoma.
AB  - A 48-year-old woman developed hepatic metastases from malignant pheochromocytoma
      resected 8 years previously. Angiography revealed multiple tumor stains in the
      liver. Transcatheter oily chemoembolization using styrenomaleic acid
      neocarzinostatin and iodized oil was performed. The patient complained of severe
      right upper quadrant pain immediately following the transcatheter oily
      chemoembolization. Necrotizing cholecystitis developed on the 4th day post
      transcatheter oily chemoembolization, hepatic infarction on the 12th day, and a
      biloma on the 19th day. Despite the administration of antibiotics and
      percutaneous transhepatic drainage, neither the volume of drainage nor the size
      of the biloma decreased. Biliary reconstruction was performed using a metallic
      stent, which decreased the size of the biloma.

PMID- 9932637
TI  - Prader-Willi syndrome with elevated follicle stimulating hormone levels and
      diabetes mellitus.
AB  - A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to
      hyperglycemia. After diet therapy and transient insulin administration, his blood
      glucose levels improved. Based on the fact that his urinary C-peptide levels
      increased, the diabetes mellitus may have been due to insulin resistance with
      obesity. In addition, his testes had become atrophied. Testosterone levels
      remained low even after human chorionic gonadotropin (HCG) administration.
      Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH)
      administration. The LH response increased slightly after daily LHRH
      administration, indicating hypothalamic hypogonadism. Follicle stimulating
      hormone (FSH) levels were, however, high and increased after LHRH administration.
      The selective FSH elevation may have been due to the accompanying idiopathic
      oligospermia.

PMID- 9932638
TI  - Mediastinal germ cell tumor complicated by visceral hemangiomatosis.
AB  - This report describes an extremely rare combination of mediastinal germ cell
      tumor and visceral hemangiomatosis in a 17-year-old boy who initially presented
      with chest pain and dyspnea. He was treated with chemotherapy consisting of
      cisplatin, cyclophosphamide, bleomycin, vinblastine, and dactinomycin followed by
      surgery. Multiple low-density nodules developed in the spleen three weeks later,
      suggesting metastases from the primary tumor, but the resected specimen showed
      cavernous hemangiomas within the splenic parenchyma. The patient died of
      recurrence of germ cell tumor 19 months after the initial treatment. Postmortem
      examination disclosed multiple hemangiomas in the lung and liver similar to those
      in the spleen.

PMID- 9932639
TI  - Pulmonary pseudallescherioma associated with systemic lupus erythematosus.
AB  - We report a case of fungus ball due to Pseudallescheria boydii
      (pseudallescherioma) associated with systemic lupus erythematosus. Direct
      microscopical examination revealed a fungus with broad septate hyphae resembling
      Aspergillus and the fungus was identified as P. boydii on culture. Surgical
      resection was required to control episodes of hemoptysis. Cases of pulmonary
      pseudallescheriasis are rare, especially in Japan. However, some cases previously
      diagnosed as pulmonary aspergillosis may have been found to be caused by P.
      boydii, if adequate culture studies had been conducted. Unlike Aspergillus, P.
      boydii is resistant to amphotericin B. Therefore, we emphasize the importance of
      a correct diagnosis based on culture examination.

PMID- 9932640
TI  - Allogeneic peripheral blood stem cell transplantation for the treatment of
      refractory follicular lymphoma.
AB  - A 38-year-old male with follicular lymphoma at clinical stage IV failed to
      achieve complete remission (CR), and developed leukemic change. After the patient
      was further treated with intensive chemotherapy for acute lymphoblastic leukemia,
      lymphoma cells in the peripheral blood and bone marrow disappeared, but the bulky
      mass persisted. Then, the patient received allogeneic peripheral blood stem cell
      transplantation (allo-PBSCT) from his human lymphocyte antigen (HL A)-identical
      brother following high-dose cyclophosphamide and 12 Gy total body irradiation,
      and the patient achieved CR with the disappearance of Bcl-2 rearrangement. The
      patient is now alive in continuous CR for more than 19 months after allo-PBSCT.

PMID- 9932641
TI  - Fatal liver cirrhosis and esophageal variceal hemorrhage in a patient with type
      IIIa glycogen storage disease.
AB  - A 45-year-old woman with type IIIa glycogen storage disease (GSD IIIa) died of
      variceal hemorrhage secondary to liver cirrhosis. The postmortem examination
      disclosed increased intracellular glycogen in the liver as well as in the heart
      and skeletal muscle. Although most liver injuries in GSD IIIa have been
      considered to be non-progressive in adulthood, liver cirrhosis can be a cause of
      death in some patients.

PMID- 9932642
TI  - Two patients with polymyositis or dermatomyositis complicated with massive
      pleural effusion.
AB  - Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with
      massive pleural effusion are reported here. Both patients presented a high-grade
      fever, pleural effusion prominent on the right, and good response to steroid
      therapy. In a 50-year-old woman with PM, combined process of pleural
      inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be
      responsible for the accumulation of the massive pleural effusion. However, in a
      34-year-old man with DM, pleural inflammation associated with interstitial
      pneumonia or pleural microvasculopathy in DM was considered to be responsible for
      the accumulation of the massive pleural effusion.

PMID- 9932643
TI  - Kimura's disease associated with bronchial asthma presenting eosinophilia and
      hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD
      1151T).
AB  - A 29-year-old man developed atopic bronchial asthma in association with
      eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an
      inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T
      (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE
      as well as the serum level of eosinophil cationic protein (ECP). The drug,
      however, did not affect the positivity for specific IgE antibodies against common
      allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)
      2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were
      measured to be undetectable in serum before or during therapy. However, the
      expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral
      blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood
      eosinophils were detected before and during therapy, which were unchanged by
      therapy with IPD-1151T. The present results suggest that different mechanisms
      other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may
      underlie Kimura's disease and atopic bronchial asthma regarding the findings of
      eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.

PMID- 9932644
TI  - First sporadic cases of non-pneumonic legionellosis, Pontiac fever in Japan.
AB  - Pontiac fever has rarely been found in sporadic cases. Here, we report the first
      sporadic cases of non-pneumonic legionellosis, Pontiac fever in Japan. Case 1. A
      53-year-old man with spinocerebellar degeneration was presented to our hospital.
      He had an acute onset of high fever and consciousness disturbance. A chest X-ray
      film on admission was normal, but transient bilateral pleural effusions were
      revealed on hospital day 14. Case 2. A 77-year-old woman with gastric ulcer was
      presented to our hospital. She had an acute onset of high fever. A chest X-ray
      film on admission was normal, but transient bilateral pleural effusions were
      revealed on hospital day 7. High fever, resistant to beta-lactam antibiotics,
      continued in both cases. Both had serologic confirmation of legionellosis by
      indirect fluorescent antibody assay for Legionella pneumophila without
      seroconversion for Mycoplasma pneumoniae, and Chlamydia pneumoniae, and had a
      good prognosis. Both were thought to be sporadic community-acquired cases rather
      than epidemics.

PMID- 9932646
TI  - Electron tomography of mitochondria from brown adipocytes reveals crista
      junctions.
AB  - Electron microscope tomography was used to examine the membrane topology of brown
      adipose tissue (BAT) mitochondria prepared by cryofixation or chemical fixation
      techniques. These mitochondria contain an uncoupling protein which results in the
      conversion of energy from electron transport into heat. The three-dimensional
      reconstructions of BAT mitochondria provided a view of the inner mitochondrial
      membrane different in important features from descriptions found in the
      literature. The work reported here provides new insight into BAT mitochondria
      architecture by identifying crista junctions, including multiple junctions
      connecting a crista to the same side of the inner boundary membrane, in a class
      of mitochondria that have no tubular cristae, but only lamellar cristae. Crista
      junctions were defined previously as the tubular membranes of relatively uniform
      diameter that connect a crista membrane with the inner boundary membrane. We have
      also found that the cristae architecture of cryofixed mitochondria, including
      crista junctions, is similar to that found in chemically fixed mitochondria,
      suggesting that this architecture is not a fixation artifact. The stacks of
      lamellar cristae extended through more of the BAT mitochondrial volume than did
      the cristae we observed in neuronal mitochondria. Hence, the inner membrane
      surface area was larger in the former. In chemically fixed mitochondria, contact
      sites were easily visualized because the outer and inner boundary membranes were
      separated by an 8 nm space. However, in cryofixed mitochondria almost all the
      outer membrane was observed to be in close contact with the inner boundary
      membrane.

PMID- 9932645
TI  - Characterization of the yeast mitochondria unselective channel: a counterpart to
      the mammalian permeability transition pore?
AB  - Large and unselective permeabilities through the inner membrane of yeast
      mitochondria have been observed for more than 20 years, but the characterization
      of these permeabilities, leading to hypothesize the existence of a large
      conductance unselective channel in yeast inner mitochondrial membrane, was done
      only recently by several groups. This channel has been tentatively identified as
      a yeast counterpart to the mammalian permeability transition pore, the crucial
      role of which is now well-documented in physiopathological phenomena, such as
      Ca2+ homeostasis, ischemic damages, or programmed cell death. The aim of this
      review is to make a point on the known characteristics of this yeast
      mitochondrial unselective channel (YMUC) and to analyze whether or not it can be
      considered as a "yeast permeability transition pore."

PMID- 9932647
TI  - Studies of the electron transport chain of the euryarcheon Halobacterium
      salinarum: indications for a type II NADH dehydrogenase and a complex III analog.
AB  - The components involved in the respiratory system of the euryarcheon
      Halobacterium salinarum were investigated by spectroscopic and polarographic
      techniques. Previous results about the cytochrome composition could be verified.
      However, under low oxygen tension, the expression of a d-type cytochrome was
      detected. Membranes exerted an NADH- and succinatecytochrome-c oxidoreductase as
      well as an NADH and succinate oxidase activity. These activities could be blocked
      by the following inhibitors: 7-jodocarboxylic acid, giving evidence for the
      presence of a type II NADH dehydrogenase, antimycin A, and myxothiazol,
      indicating the presence of a complex III analog, and the typical succinate
      dehydrogenase (SDH) and terminal oxidase inhibitors. Complex I inhibitors like
      rotenone and annonine were inactive, clearly excluding the presence of a coupled
      NADH dehydrogenase. In addition, no [Fe-S] resonances in the region of the NADH
      dehydrogenase (NDH) clusters could be observed after NADH addition. One of the
      terminal oxidases could be shown to act as a cytochrome-c oxidase with a Km value
      of 37 microM and an activation energy of 23.7 kJ/mol. The relative molecular mass
      of the endogenous c-type cytochrome could be determined as 14.1 kD. The complex
      III analog could be enriched after detergent extraction with Triton X-100 and
      hydroxylapatite (HTP) chromatography. The partially purified complex contained a
      Rieske iron-sulfur cluster, b- and c-type cytochromes, and was catalytically
      active in the decylubiquinone-cytochrome-c oxidoreductase assay.

PMID- 9932648
TI  - Exogenous ubiquinol analogues affect the fluorescence of NCD-4 bound to aspartate
      160 of yeast cytochrome b.
AB  - Previously, we reported that the carboxyl-reacting reagent DCCD, and its
      fluorescent derivative NCD-4 binds covalently to aspartate-160 localized in
      amphipathic helix cd of the CD loop connecting membrane-spanning helices C and D
      of cytochrome b (Wang et al., 1995). We have investigated the fluorescent
      properties of NCD-4 to probe possible changes in the cd helix resulting from the
      binding of exogenous ubiquinol analogues to the bc1 complex. Preincubation of the
      bc1 complex with the reduced substrate analogues, DQH2, DBH2, and Q6H2 resulted
      in 20-40% increase in the fluorescence emission intensity of NCD-4 and a 10-20%
      increase in the binding of [14C]DCCD to the bc1 complex. By contrast,
      preincubation with the oxidized analogues DQ. DB, and Q6 resulted in a 20-40%
      decrease in the fluorescence emission intensity of NCD-4 and a 20-40% decrease in
      the binding of [14C]DCCD to the bc1 complex. Moreover, addition of the reduced
      ubiquinols to the bc1 complex preincubated with NCD-4 resulted in a blue shift in
      the fluorescence emission spectrum. In addition, incubation of the cytochrome bc1
      complex reconstituted into proteoliposomes with both reduced and oxidized
      ubiquinol analogues resulted in changes in the quenching of NCD-4 fluorescence by
      CAT-16, the spin-label probe that intercalates at the membrane surface. These
      results indicate that the addition of exogenous ubiquinol to the bc1 complex may
      result in changes in the cd helix leading to a more hydrophobic environment
      surrounding the NCD-4 binding site. By contrast, preincubation with the
      inhibitors of electron transfer through the bc1 complex had no effect on the
      binding of NCD-4 to the bc1 complex or on the fluorescent emission spectra, which
      suggests that the binding of the inhibitors does not result in changes in the
      environment of the NCD-4 binding site.

PMID- 9932649
TI  - Genetic evidence for coenzyme Q requirement in plasma membrane electron
      transport.
AB  - Plasma membranes isolated from wild-type Saccharomyces cerevisiae crude membrane
      fractions catalyzed NADH oxidation using a variety of electron acceptors, such as
      ferricyanide, cytochrome c, and ascorbate free radical. Plasma membranes from the
      deletion mutant strain coq3delta, defective in coenzyme Q (ubiquinone)
      biosynthesis, were completely devoid of coenzyme Q6 and contained greatly
      diminished levels of NADH-ascorbate free radical reductase activity (about 10% of
      wild-type yeasts). In contrast, the lack of coenzyme Q6 in these membranes
      resulted in only a partial inhibition of either the ferricyanide or cytochrome-c
      reductase. Coenzyme Q dependence of ferricyanide and cytochrome-c reductases was
      based mainly on superoxide generation by one-electron reduction of quinones to
      semiquinones. Ascorbate free radical reductase was unique because it was highly
      dependent on coenzyme Q and did not involve superoxide since it was not affected
      by superoxide dismutase (SOD). Both coenzyme Q6 and NADH-ascorbate free radical
      reductase were rescued in plasma membranes derived from a strain obtained by
      transformation of the coq3delta strain with a single-copy plasmid bearing the
      wild type COQ3 gene and in plasma membranes isolated form the coq3delta strain
      grown in the presence of coenzyme Q6. The enzyme activity was inhibited by the
      quinone antagonists chloroquine and dicumarol, and after membrane solubilization
      with the nondenaturing detergent Zwittergent 3-14. The various inhibitors used
      did not affect residual ascorbate free radical reductase of the coq3delta strain.
      Ascorbate free radical reductase was not altered significantly in mutants
      atp2delta and cor1delta which are also respiration-deficient but not defective in
      ubiquinone biosynthesis, demonstrating that the lack of ascorbate free radical
      reductase in coq3delta mutants is related solely to the inability to synthesize
      ubiquinone and not to the respiratory-defective phenotype. For the first time,
      our results provide genetic evidence for the participation of ubiquinone in NADH
      ascorbate free radical reductase, as a source of electrons for transmembrane
      ascorbate stabilization.

PMID- 9932650
TI  - The sulfonylurea-inhibited NADH oxidase activity of HeLa cell plasma membranes
      has properties of a protein disulfide-thiol oxidoreductase with protein disulfide
      thiol interchange activity.
AB  - Plasma membrane vesicles of HeLa cells are characterized by a drug-responsive
      oxidation of NADH. The NADH oxidation takes place in an argon or nitrogen
      atmosphere and in samples purged of oxygen. Direct assay of protein thiols by
      reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB; Ellman's reagent),
      suggests that protein disulfides may be the natural electron acceptors for NADH
      oxidation by the plasma membrane vesicles. In the presence of NADH, protein
      disulfides of the membranes were reduced with a concomitant stoichiometric
      increase in protein thiols. The increase in protein thiols was inhibited in
      parallel to the inhibition of NADH oxidation by the antitumor sulfonylurea
      LY181984 with an EC50 of ca. 30 nM. LY 181984, with an EC50 of 30 nM, also
      inhibited a protein disulfide-thiol interchange activity based on the restoration
      of activity to inactive (scrambled) RNase and thiol oxidation. The findings
      suggest that thiol oxidation, NADH-dependent disulfide reduction (NADH
      oxidation), and protein disulfide-thiol interchange in the absence of NADH all
      may be manifestations of the same sulfonylurea binding protein of the HeLa plasma
      membrane. A surface location of the thiols involved was demonstrated using
      detergents and the impermeant thiol reagent p-chloromercuriphenylsulfonic acid
      (PCMPS). The surface location precludes a physiological role of the protein in
      NADH oxidation. Rather, it may carry out some other role more closely related to
      a function in growth, such as protein disulfide-thiol interchange coupled to cell
      enlargement.

PMID- 9932651
TI  - Advances in the purification of the mitochondrial Ca2+ uniporter using the
      labeled inhibitor 103Ru360.
AB  - For many years the calcium uniporter has eluded attempts of purification, partly
      because of the difficulties inherent in the purification of low-abundance
      hydrophobic proteins (Reed and Bygrave, 1974). Liquid-phase preparative
      isoelectric focusing improved the fractionation of mitochondrial membrane
      proteins. A single 6-h run resulted in a 90-fold increase in specific activity of
      pooled active fractions over a semipurified fraction, allowing for enrichment of
      the calcium transport function in cytochrome oxidase vesicles. An additional
      powerful tool in the isolation of the uniporter was the use of the labeled
      inhibitor 103Ru360 as an affinity ligand; by following this procedure a protein
      of 18 kDa was purified in nondenatured, but rather inactive, form. The labeled
      protein corresponds to the protein that showed Ca2+ transport activity.

PMID- 9932653
TI  - Treatment of peritoneal dialysis catheter-related infections by simultaneous
      catheter removal and replacement. Is it safe?

PMID- 9932652
TI  - Voltage-dependent anion channel proteins in synaptosomes of the torpedo electric
      organ: immunolocalization, purification, and characterization.
AB  - In this study, we purified and characterized the voltage-dependent anion channel
      (VDAC) from the Torpedo electric organ. Using immunogold labeling, VDAC was
      colocalized with the voltage-gated Ca2+ channel in the synaptic plasma membrane.
      By immunoblot analysis, five protein bands in synaptosomes isolated from the
      Torpedo electric organ cross reacted with two monoclonal anti-VDAC antibody. No
      more than about 7 to 10% mitochondrial contains could be detected in any
      synaptosomal membrane preparation tested. This was estimated by comparing the
      specific activity in mitochondria and synaptosomes of succinate-cytochrome-c
      oxidoreductase and antimycin-insensitive NADH-cytochrome-c oxidoreductase
      activities; mitochondrial inner and outer membrane marker enzymes, respectively.
      [14C]DCCD (dicyclohexylcarbodiimide), which specifically label mitochondrial
      VDAC, labeled four 30-35 kDa protein bands that were found to interact with the
      anti-VDAC antibody. The distribution of the Torpedo VDAC protein bands was
      different among membranes isolated from various tissues. VDAC was purified from
      synaptosomes and a separation between two of the proteins was obtained. The two
      purified proteins were characterized by their single channel activity and partial
      amino acid sequences. Upon reconstitution into a planar lipid bilayer, the
      purified VDACs showed voltage-dependent channel activity with properties similar
      to those of purified mitochondrial VDAC. Amino acid sequence of four peptides,
      derived from VDAC band II, exhibited high homology to sequences present in human
      VDACI (98%), VDAC2 (91.8%), and VDAC3 (90%), while another peptide, derived from
      VDAC band III, showed lower homology to either VDAC1 (88.4%) or VDAC2 (79%). Two
      more peptides show high homology to the sequence present in mouse brain VDAC3
      (100 and 78%). In addition, we demonstrate the translocation of ATP into
      synaptosomes, which is inhibited by DCCD and by the anion transport inhibitor
      DIDS. The possible function of VDAC in the synaptic plasma membrane is discussed.

PMID- 9932654
TI  - Serum leptin correlates with fat mass but not dietary energy intake in continuous
      ambulatory peritoneal dialysis patients.
AB  - OBJECTIVES: In view of previous studies demonstrating hyperleptinemia in uremic
      and hemodialysis patients, the aims of the present study were to determine
      whether serum leptin levels are elevated in peritoneal dialysis (PD) patients, to
      establish whether leptin is significantly removed by PD, and to elucidate the
      relationship of plasma leptin to body composition, dietary intake, nutritional
      indices, and dialysis adequacy. DESIGN: Cross-sectional analysis of PD patients
      and matched healthy controls. SETTING: Tertiary-care institutional dialysis
      center. PARTICIPANTS: The study included 49 PD patients [35 women and 14 men;
      median age 63 years, interquartile range (IQR) 49.5-68.5 yr; body mass index
      (BMI) 25.5 +/- 0.8] and 27 controls (11 men and 16 women; median age 42 years,
      IQR 34.8-51; BMI 27.2 +/- 0.9). For evaluation of leptin clearance, 8 patients
      receiving nocturnal intermittent PD were also evaluated. MAIN OUTCOME MEASURES:
      The primary outcome measure was plasma leptin concentration. Dialysate leptin
      concentration was also measured in 7 patients. RESULTS: Serum leptin levels were
      significantly higher (p < 0.01) in patients (males: median 11 ng/mL, IQR 9-19
      ng/mL; females: 53 ng/mL, 19.5-128 ng/mL) compared with controls (males: 5.5
      ng/mL, 4-9.5 ng/mL; females: 12 ng/mL, 9.8-17.3 ng/mL). Leptin levels in both
      groups correlated positively with BMI (r = 0.64 and 0.60, respectively; p <
      0.0001) and with percentage body fat determined by dual-energy x-ray
      absorptiometry (r = 0.86 and 0.82, respectively; p < 0.01). Dialysis patients
      exhibited a greater increase in serum leptin for any given increase in BMI. No
      significant correlation was observed between leptin concentration and residual
      renal function, dialysis adequacy (Kt/V), dietary protein or caloric intake, or
      serum levels of albumin, prealbumin, C-reactive protein, glucose, and insulin
      like growth factor-I. Although leptin was detectable in peritoneal dialysate
      after a 6-hour dwell (median 4.2 ng/mL, IQR 1.1-8.5 ng/mL, n = 8), serum leptin
      levels were not appreciably lowered following intermittent PD via an automated
      cycler (63.9 +/- 19.3 ng/mL vs 57.6 +/- 20.5 ng/mL, p = NS, n = 8). CONCLUSIONS:
      Serum leptin levels are elevated in PD patients and are not appreciably cleared
      by PD. Although hyperleptinemia correlates poorly with dialysis adequacy and
      protein intake, a strong and significant relationship was maintained between
      serum leptin and fat mass. Serum leptin could therefore serve as a useful
      clinical marker of body fat content in PD patients.

PMID- 9932655
TI  - Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis
      solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized
      cross-over study, 8 patients were randomized in two groups of 4. On the first
      study day, the first group performed two consecutive 4-hour exchanges with a
      dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L
      and the second with 38.6 g/L dextrose. On the second study day, the same type of
      exchanges were performed with bicarbonate. The second group underwent the same
      treatment, but used bicarbonate solutions on the first day and control solutions
      on the second study day. Thirty-three patients participated in a 2-month
      prospective and randomized study. After a 4-week baseline period using solutions
      containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L
      bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal
      dialysis units at the University Hospital of Brescia and the Niguarda Hospital of
      Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar
      effects on blood chemistries and peritoneal transport. Chronic study: Mean venous
      bicarbonate concentrations remained unchanged in the control group (26.6-27.2
      mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at
      the start of the study to 23.0 mmol/L after 2 months of bicarbonate
      administration. Other biochemical parameters remained unchanged. CONCLUSION: A
      peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not
      adequately correct uremic acidosis.

PMID- 9932656
TI  - Nystatin prophylaxis: its inability to prevent fungal peritonitis in patients on
      continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To evaluate the potential effectiveness of nystatin as prophylaxis for
      fungal peritonitis (FP) in patients on continuous ambulatory peritoneal dialysis
      (CAPD). DESIGN: This historically controlled study was designed to investigate
      the effectiveness of nystatin in the prevention of FP. For this purpose we
      compared the incidence of FP among 240 (new and prevalent) CAPD patients between
      January 1996 and November 1996 (period A) with its incidence in 240 new and
      prevalent CAPD patients in our program between January 1997 and November 1997
      (period B) when nystatin prophylaxis was used. There were 2400 patient-months in
      each period. Nystatin (500,000 IU four times per day), was given orally at the
      beginning of other antibiotic therapy (usually for peritonitis) and continued for
      5 days after the end of the antibiotic therapy. RESULTS: During period A, 133
      peritonitis episodes were recorded, and during period B, 99 episodes were
      recorded. Six episodes of FP were identified in over 2400 patient-months of
      period A, and 12 in over 2400 patient-months of period B. This difference was not
      statistically significant. Three episodes of antibiotic-related FP were seen in
      period A, and four in period B. The remaining episodes arose de novo, that is,
      unrelated to the use of antibiotics. We observed no side effects for nystatin.
      CONCLUSION: In CAPD patients the use of nystatin, a nonabsorbable antifungal
      agent, as prophylaxis in every instance of peritonitis or other indications for
      antibiotics, did not lower the incidence of fungal peritonitis.

PMID- 9932657
TI  - Influence of age, time, and peritonitis on peritoneal transport kinetics in
      children.
AB  - OBJECTIVE: To evaluate peritoneal transport kinetics and its changes over time in
      children with and without peritonitis, and to record possible differences between
      children under and over 5.0 years of age. DESIGN: A prospective study. The
      patients underwent a 4-hour peritoneal equilibration test (PET) comprising 2.27%
      dextrose with a dialysate fill volume of 1000 mL/m2 of body surface area (BSA),
      at baseline and after a mean of 0.8 +/- 0.4 years of uninterrupted dialysis.
      PATIENTS: We investigated 28 patients on maintenance peritoneal dialysis at
      baseline; 10 were under 5.0 years of age. The final PET was performed in 21
      patients. MAIN OUTCOME MEASURES: Peritoneal equilibration rates for urea (U),
      creatinine (C), glucose (G), sodium, potassium, phosphate, and albumin (A) were
      measured. Initial and final peritoneal equilibration rates were compared. Mass
      transfer area coefficients (MTAC) were calculated for urea, creatinine, glucose,
      and albumin. Residual dialysate volume was determined. RESULTS: Median age at
      first PET was 7.6 years (range 0.3-16.6 yr). The mean (+/- 1 SD) 4-hour dialysate
      to-plasma (D/P) ratios for U, C, and A were 0.92 +/- 0.05, 0.70 +/- 0.12, and
      0.014 +/- 0.007, respectively. The mean 4-hour D/D0 ratio for G was 0.32 +/-
      0.10. D/P and D/D0 results were similar in the two age groups, and peritoneal
      membrane function remained stable over the study period. Mean MTAC (+/- 1 SD)
      values were: U, 22.3 +/- 4.8; C, 10.9 +/- 4.1; G, 11.1 +/- 3.3; and A, 0.07 +/-
      0.03. MTAC data were similar in the two age groups and no significant changes
      occurred during the study period. CONCLUSIONS: When the volume tested in children
      is proportional to BSA, the solute D/P ratios seem to be age-independent. Our
      data provide evidence that in pediatric patients MTAC is also age-independent.

PMID- 9932658
TI  - Six-year experience with Swan neck presternal peritoneal dialysis catheter.
AB  - BACKGROUND: The presternal peritoneal catheter is composed of two silicone rubber
      tubes joined by a titanium connector at the time of implantation, and has an exit
      on the chest. OBJECTIVE: Comparison of survival and complication rates of Swan
      neck abdominal catheters with those of the presternal catheter. DESIGN:
      Nonrandomized study with prospective collection of data between August 1991 and
      October 1997. SETTING: Tertiary referral center. PATIENTS: In 57 patients, 58
      presternal catheters and, in 81 patients, 86 abdominal catheters were implanted.
      Patients chose the type of catheter; however, obese individuals and those with
      ostomies and previous catheter problems were encouraged to opt for the presternal
      catheter. Others chose the presternal catheter in order to take tub baths or use
      a whirlpool. MAIN OUTCOME MEASURES: Life-table analyses of catheter survival
      censored for transplant, transfer, and death; reasons for catheter removal due to
      complications; and patient satisfaction. RESULTS: Two-year survival probabilities
      were 0.95 and 0.75 for presternal and abdominal catheters, respectively. Nine
      abdominal catheters were removed due to exit/tunnel infections (including five
      with peritonitis), and four due to peritonitis. External cuff shaving in four
      presternal catheters has extended survival for more than 1 year. Four presternal
      catheters were removed due to peritonitis. No catheters in either group were lost
      due to leakage or obstruction. The peritonitis rate was 1 episode per 37.4
      patient-months and 1/20.5 patient-months for presternal and abdominal catheters,
      respectively. These differences are not significant. Patient acceptance of the
      presternal catheters was excellent; in the latest period, from January to October
      1997, presternal catheters were chosen by 15/24 patients. CONCLUSIONS: The trend
      to improved outcomes in presternal catheters continues to validate the rationale
      for presternal catheter design. Decreased frequency of exit/tunnel infection may
      be due to more effective immobilization on the chest, less trauma, and avoidance
      of submersion in stagnant water. No specific contraindications to use of the
      presternal catheter have been identified.

PMID- 9932659
TI  - A previously undescribed side effect of icodextrin: overestimation of glycemia by
      glucose analyzer.
AB  - OBJECTIVE: Serious discrepancies between glycemia measurements obtained with an
      Accutrend Sensor (Boehringer Mannheim GmbH, Mannheim, Germany) type analyzer
      (based on a glucose dehydrogenase enzymatic reaction) and measurements obtained
      in the laboratory by a reference method (hexokinase) have been found in an
      insulin-requiring, diabetic, continuous ambulatory peritoneal dialysis (CAPD)
      patient treated with icodextrin 7.5% (Extraneal; Baxter Healthcare SA, Castlebar,
      Ireland), a new osmotic agent for peritoneal dialysis. We therefore investigated
      the respective role of the Analyzer and of the glucose polymer in this hitherto
      undescribed problem. DESIGN: Glycemia was measured simultaneously on venous blood
      using a reference laboratory technique, and on capillary blood using the
      Accutrend Sensor glucose analyzer in three groups of CAPD patients: 6 patients on
      Extraneal for at least 1 week, 6 patients receiving their first Extraneal
      exchange, and 8 patients never exposed to Extraneal. In the first group of
      patients, glycemia was also measured with another analyzer (Glucocard; Menarini
      Diagnostics, Firenze, Italy) using a different enzymatic reaction (glucose
      oxidase). In a separate study, whole blood of a normal subject was spiked with
      concentrated solutions of glucose and icodextrin and some of its metabolites
      (maltose, maltotriose, maltopentaose). Once again, comparative measurements of
      glycemia were performed with the Accutrend Sensor, with two other kits using a
      glucose dehydrogenase enzyme reaction, and with the hexokinase reference method.
      RESULTS: In 6 CAPD patients treated with once-daily exchanges with Extraneal for
      a minimum of 7 consecutive days, we confirmed overestimation of glycemia by the
      Accutrend Sensor of 65 +/- 26 mg/dL compared to reference values (p < 0.01), and
      of 69 +/- 25 mg/dL (p < 0.001) compared to measurements obtained with the
      Glucocard monitor. In 6 other CAPD patients studied at the end of one single
      icodextrin exchange, overestimation of 61 +/- 11 mg/dL was already present (p <
      0.001). On the other hand, in 8 CAPD patients never treated with icodextrin,
      there was no discrepancy between the Accutrend Sensor readings and reference
      values. The measurements in spiked blood confirmed that only the Accutrend Sensor
      overestimates glycemia in the presence of maltose and glucose polymers. The
      overestimation decreased as the molecular size of the saccharides added to blood
      increased. There was no overestimation when other kits using a dehydrogenase
      enzyme were tested. CONCLUSION: The overestimation observed is probably related
      to the presence of oligosaccharides (mainly maltose), derivatives of glucose
      polymers present in Extraneal and absorbed via the peritoneal route, in the blood
      of patients treated with icodextrin. The glucose dehydrogenase characterizing the
      Accutrend Sensor, an enzyme of the pyrroloquinolinequinone class, very likely
      reacts with the free reducing group of the glucose molecule located at the end of
      each saccharide chain. This would not be the case for the Glucocard monitor using
      glucose oxidase, for other kits using glucose dehydrogenase, and for the
      reference method based on hexokinase. The Accutrend Sensor type of analyzers are
      therefore not suitable for regular monitoring of glycemia in diabetic PD patients
      treated with icodextrin.

PMID- 9932660
TI  - Biocompatibility of a peritoneal dialysis solution with amino acids: histological
      evaluation in the rabbit.
AB  - OBJECTIVE: To determine the biocompatibility of a peritoneal dialysis (PD)
      solution containing amino acids compared to PD solutions containing glucose.
      DESIGN: The biocompatibility of three dialysis solutions containing 1.1% amino
      acids, 1.36% glucose, and 3.86% glucose, respectively, was evaluated in vivo in
      rabbits. METHODS: After 60 days of PD, peritoneal histological changes in rabbits
      were investigated by light and transmission electron microscopy. The parameters
      investigated were: (1) mesothelial damage; (2) submesothelial edema; (3)
      submesothelial cell infiltration; (4) submesothelial fibrosis; and (5) vascular
      alterations. Semiquantitative evaluations were performed for all the above
      alterations; quantitative morphometric evaluation was performed for mesothelial
      damage (cubic transformation of the mesothelium, areas devoid of mesothelium,
      submesothelial edema) and thickness of peritoneal arteriole walls. RESULTS: (1)
      Mesothelial damage was practically nonexistent in rabbits dialyzed with the
      solution containing amino acids, and intermediate and severe with low-glucose and
      high-glucose solutions, respectively. Both controls and rabbits dialyzed with
      amino acid solution showed flat continuous mesothelium; rabbits dialyzed with low
      glucose solution showed cubic continuous mesothelium; and rabbits dialyzed with
      high-glucose solution showed cubic discontinuous mesothelium. Cytopathic
      mesothelial effects were slight with the solution containing amino acids and
      severe with both the low- and high-glucose solutions. Duplication and thickening
      of mesothelial basement membrane were never observed. (2) Submesothelial edema
      showed a worsening trend from controls to rabbits dialyzed with solution
      containing amino acids, low glucose, and high glucose. (3) No difference in
      submesothelial infiltration was found between groups. (4) Submesothelial fibrosis
      was never observed. (5) Vascular alterations were never observed. CONCLUSION:
      These results are evidence that PD solution with amino acids is more
      biocompatible than high- and also low-glucose solutions.

PMID- 9932661
TI  - Plasticizers and inhibition of leukocyte function in vitro.
AB  - OBJECTIVES: To evaluate the influence of the plasticizer metabolites of di(2
      ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol
      (2-EH), and phthalic acid (PA) on various immune functions of polymorphonuclear
      blood leukocytes (PMNL) and monocytes (MN). MEHP, 2-EH, and PA are the main
      hydrolysis products of DEHP. Since DEHP is leached out of the plastic matrix,
      patients on hemodialysis and continuous ambulatory peritoneal dialysis are
      exposed to considerable amounts of DEHP and its metabolites. SETTING: Teaching
      hospital, Department of Nephrology. PARTICIPANTS: Ten healthy volunteers.
      MEASUREMENTS: After incubation of leukocytes in solutions with different
      plasticizer concentrations, oxidative respiratory metabolism was determined by
      luminol-enhanced chemiluminescence (CL) after stimulation with phorbol myristate
      acetate (PMA). Furthermore, superoxide (O2-) generation was measured by
      cytochrome c reduction. RESULTS: At pH 5.4, a dose-dependent decrease of luminol
      enhanced CL response was found in all assays. For MEHP and PA the level of
      significance was reached at 10 mg/L and 1 mg/L, respectively. Superoxide
      generation by PMNL and MN at pH 5.4 was also suppressed by MEHP and PA. At pH
      7.4, only a slight suppression of oxidative metabolism at higher concentrations
      was observed. After incubation of the cells in a solution containing all DEHP
      metabolites (MEHP, PA, and 2-EH), a significant suppressive effect of CL at pH
      5.4 could be observed at final plasticizer concentrations of 0.5 mg/L.
      CONCLUSIONS: A dose-dependent impairment of leukocyte oxidative metabolism at a
      low pH could be demonstrated. The suppressive effect was particularly marked
      after incubation of the cells in solutions containing a mixture of the main
      plasticizers. At pH 5.4, we observed a slight alteration even at concentrations
      very close to those that could be found in commercially available peritoneal
      dialysis fluids. These results might point toward a possible synergistic
      detrimental effect of the different DEHP metabolites on leukocyte function, with
      possible clinical relevance.

PMID- 9932662
TI  - Mast cell histamine-induced calcium transients in cultured human peritoneal
      mesothelial cells.
AB  - OBJECTIVE: Peritoneal inflammation results from a complex interplay of events
      initiated by macrophage activity in response to infection, with the stimulation
      of mesothelial cell cytokine release amplifying the recruitment of blood-borne
      defense cells to the site of injury. Resident peritoneal mast cells may add to
      this complexity with mast cell derived cytokines released during this cascade.
      This study examined the influence of histamine, a mast cell-derived inflammatory
      mediator, on the initial activation of human peritoneal mesothelial cells (HPMC)
      by intracellular free calcium (Ca2+(i)) mobilization, and changes to the actin
      cytoskeleton. DESIGN: HPMC signal transduction was examined in response to
      histamine (1.0 mmol/L) compared to fetal bovine serum (FBS) (0.1%) and 4-br
      A23187 (1.0 micromol/L). Intracellular free calcium was measured in fura-2 loaded
      cells with and without external calcium (Ca2+(ext)), or Ca2+(ext) with verapamil
      (100 micromol/L). Following treatment with agonists, HPMC actin cytoskeleton was
      stained using direct immunocytochemistry. RESULTS: HPMC responded to histamine
      with a twofold transient rise in Ca2+(i) which returned to the baseline, in
      contrast with FBS- and A23187-induced Ca2+(i) transients, which returned to
      elevated resting values. In the absence of Ca2+(ext), all agents produced a
      calcium transient indicative of calcium release from intracellular stores.
      Histamine induced calcium-dependent changes to the cytoskeleton and cellular
      organization, including increased actin stress fibers. CONCLUSION: Histamine
      produced large specific receptor-mediated calcium transients in HPMC, which
      included components of calcium release from intracellular stores and receptor
      mediated calcium influx processes. The observed response to histamine raises the
      possibility that histamine derived from resident mast cells may modulate
      mesothelial cell function, in part by calcium-dependent pathways, and influence
      the performance of the peritoneal membrane during peritoneal dialysis.

PMID- 9932663
TI  - Pseudomonas exit-site infections in CAPD patients: evolution and outcome of
      treatment.
AB  - OBJECTIVE: To examine the natural history of Pseudomonas aeruginosa (PSA) exit
      site infections (ESI) in patients treated with antibiotics with or without
      surgical interventions. DESIGN: Retrospective record review from May 1994 to
      April 1997. SETTING: A single dialysis unit in a district hospital. PATIENTS: The
      review included 353 patients who had undergone continuous ambulatory peritoneal
      dialysis (CAPD). OUTCOME MEASURES: The prevalence and etiology of ESI, the
      treatment regimen for PSA ESI, and the outcome of treatment. RESULTS: The
      prevalence of ESI was 55%. A total of 131 episodes (range 1-5) of PSA ESI
      occurred in 78 (40.2%) of the 194 patients who experienced ESI. Among these 78
      patients, 4 groups with different outcomes were identified. In group I, 35
      patients (44.9%) were treated successfully with antibiotic therapy alone. Among
      these 35 patients, 4 developed PSA peritonitis at a mean of 5 months (range 2-10
      mth) after apparent clinical resolution of PSA ESI. Two of the 4 patients
      switched to long-term hemodialysis (HD) because of peritoneal failure. In group
      II, 8 patients (10.3%) responded to a combination of antibiotics and shaving of
      the external cuff. In group III, 21 patients (26.9%) with recurrent ESI underwent
      elective Tenckhoff catheter removal and reinsertion. One of the 21 patients had
      relapse of PSA ESI 14 months after the operation. In group IV, 14 patients
      (17.9%) had recurrent PSA ESI that failed to respond to multiple courses of
      antibiotics and shaving of the external cuff. Consent for Tenckhoff catheter
      removal was not obtained and 4 of these 14 patients subsequently developed PSA
      peritonitis. One of the 4 patients changed to permanent HD due to peritoneal
      failure. CONCLUSIONS: Considering the increased risk and the poor outcome of PSA
      peritonitis in patients with persistent PSA ESI, early Tenckhoff catheter removal
      is recommended if the patient fails to respond to antibiotics with or without
      externalization of the external cuff.

PMID- 9932664
TI  - Longitudinal changes of peritoneal solute permeability in continuous cyclic
      peritoneal dialysis and CAPD.

PMID- 9932665
TI  - Moulds in containers with biological wastes as a possible source of peritonitis
      in two patients on peritoneal dialysis.

PMID- 9932666
TI  - Automated peritoneal dialysis using amino acid dialysate in a child with
      suspected hepatic steatosis.

PMID- 9932667
TI  - Relation of calcified macroangiopathy to peritoneal small solute transport
      property.

PMID- 9932669
TI  - Gastrointestinal angiodysplastic bleeding also occurs in CAPD.

PMID- 9932668
TI  - Streptococcus equinus peritonitis in a CAPD patient.

PMID- 9932670
TI  - Therapy with gastric acid inhibitors is not related to enteric peritonitis in
      peritoneal dialysis.

PMID- 9932671
TI  - A novel use of spent peritoneal dialysis bags: an inexpensive waterbed.

PMID- 9932672
TI  - Hydrothorax in peritoneal dialysis. Effective treatment with pleurodesis.

PMID- 9932674
TI  - Literature. November-December 1998.

PMID- 9932673
TI  - Peritoneal dialysis case forum. Is it too late to put out the fire in the barn?
      What can be done?

PMID- 9932675
TI  - Nursing application: assessments of glucometers, presternal peritoneal dialysis
      catheters, peritoneal membrane function in children, and fungal prophylaxis.

PMID- 9932676
TI  - 2nd National Annual Conference of the Peritoneal Dialysis Society of India.
      August 19-20, 1998-Hyderabad.

PMID- 9932677
TI  - The thrill of victory: at what price?

PMID- 9932678
TI  - Continuous measurement of gut pH with near-infrared spectroscopy during
      hemorrhagic shock.
AB  - BACKGROUND: The rate and magnitude of pH changes in the bowel during hemorrhagic
      shock are greater than those in the stomach, implying that gastric intramucosal
      pH may not be a reliable indicator of gut perfusion. Here, we evaluate near
      infrared spectroscopy (NIRS) to assess bowel pH in a swine shock model. METHODS:
      Laparotomy was performed to place flow probes, pH microelectrodes, and NIRS
      probes. Shock was maintained for 45 minutes at a blood pressure of 45 mm Hg, and
      resuscitation was achieved with shed blood and lactated Ringer's solution to
      baseline over 60 minutes. RESULTS: Hemodynamic measurements were significantly
      reduced during shock. Lactic acid peaked during resuscitation and remained
      elevated. NIRS-measured pH was correlated to electrode-measured pH (R2 = 0.903
      [ischemia] and R2 = 0.889 [reperfusion]). Estimated measurement accuracy after
      subject-specific offset correction was 0.083 pH units during ischemia and 0.076
      pH units during reperfusion. CONCLUSION: NIRS determination of small-bowel pH may
      be a good tool to monitor the adequacy of resuscitation.

PMID- 9932679
TI  - Preload assessment in patients with an open abdomen.
AB  - BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome cause
      significant morbidity and mortality in surgical and trauma patients. Maintenance
      of intravascular preload and use of open abdomen techniques are essential. The
      accuracy of pulmonary artery occlusion pressure (PAOP) and central venous
      pressure (CVP) in patients with intra-abdominal hypertension has been questioned.
      METHODS: Twenty surgical and trauma patients with intra-abdominal hypertension
      requiring open abdominal decompression were monitored using volumetric
      thermodilution pulmonary artery catheters. Hemodynamic, oxygenation, inspiratory,
      and intravesicular pressure measurements were collected prospectively. PAOP, CVP,
      and right ventricular end-diastolic volume index (RVEDVI) were compared as
      estimates of preload status. RESULTS: Multiple regression analysis demonstrated
      that cardiac index correlated significantly better with RVEDVI (r = 0.69) than
      with PAOP (r = -0.27) or CVP (r = -0.28) during resuscitation after open
      abdominal decompression (p < 0.0001). CONCLUSION: RVEDVI is superior to PAOP and
      CVP as an estimate of preload status in patients with an open abdomen.

PMID- 9932680
TI  - Do different rates of fluid resuscitation adversely or beneficially influence
      immune responses after trauma-hemorrhage?
AB  - BACKGROUND: Although rapid fluid resuscitation continues to be an important
      component of the initial therapy for trauma patients, it remains unknown whether
      the rate of fluid administration after trauma-hemorrhage has any deleterious or
      beneficial effects on immunity. METHODS: Male C3H/HeN mice were subjected to sham
      operation or soft-tissue trauma (midline laparotomy) and hemorrhagic shock (mean
      arterial blood pressure of 35+/-5 mm Hg for 90 minutes) followed by resuscitation
      with four times the volume of shed blood in the form of lactated Ringer's
      solution over 30 minutes (rapid rate), 60 minutes (moderate rate), or 120 minutes
      (slow rate). The animals were killed at either 4 hours or 4 days after the end of
      trauma-hemorrhage. Spleens were harvested and splenocyte interleukin (IL)-3 and
      interferon-gamma (IFN-gamma) release as well as splenic macrophage IL-1beta and
      IL-6 release were determined. RESULTS: The results indicate that at 4 hours after
      trauma-hemorrhage, splenocyte IL-3 and IFN-gamma release were significantly
      depressed in all animals subjected to trauma-hemorrhage compared with sham
      operated animals. At 4 days after trauma-hemorrhage, splenocyte IL-3 and IFN
      gamma release were restored in mice resuscitated with the slow rate of
      resuscitation; however, the release of these cytokines remained significantly
      depressed in animals resuscitated with the moderate or rapid rates. Splenic
      macrophage IL-1beta and IL-6 release were significantly depressed at 4 hours
      after trauma-hemorrhage. At 4 days after trauma-hemorrhage, the release of these
      proinflammatory cytokines was still depressed in animals resuscitated with the
      rapid rate. In contrast, splenic macrophage IL-1beta and IL-6 release were
      restored in mice receiving the slow rate of resuscitation. CONCLUSION: These
      results suggest that a slower rate of fluid resuscitation after trauma-hemorrhage
      leads to a faster restoration of the depressed cell-mediated immunity, whereas
      rapid fluid resuscitation produces a prolonged depression of immune responses. In
      view of this, we propose that a prospective clinical study of this type must be
      performed in a select group of trauma patients to determine whether or not a
      slower rate of fluid resuscitation also improves immune responses in trauma
      patients.

PMID- 9932681
TI  - L-arginine: a unique amino acid for restoring the depressed macrophage functions
      after trauma-hemorrhage.
AB  - BACKGROUND: Immune responses are markedly depressed very early after the onset of
      hemorrhage. Furthermore, endothelial cell dysfunction occurs after trauma
      hemorrhage and may contribute to alterations in immune function. Recent studies
      have shown that administration of L-arginine restores the depressed organ blood
      flow, probably because of the provision of substrate for constitutive nitric
      oxide synthase. It remains unknown, however, whether administration of L-arginine
      would have any salutary effect on the depressed macrophage function after trauma
      hemorrhage. METHODS: Male rats underwent midline laparotomy (i.e., trauma was
      induced). After this, the animals were bled to and maintained at a mean blood
      pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in
      the form of lactated Ringer's solution. Sham-operated rats underwent both femoral
      artery cannulation and ligation, but these animals were neither bled nor
      resuscitated. Hemorrhaged rats were then resuscitated with lactated Ringer's
      solution, receiving four times the maximum shed blood volume over 1 hour. During
      resuscitation, one group received 300 mg/kg L-arginine and the other group
      received saline (vehicle) intravenously. At 4 hours after resuscitation, splenic
      and peritoneal macrophage interleukin (IL)-1beta and IL-6 release as well as
      plasma IL-6 were measured. RESULTS: Splenic and peritoneal macrophage IL-1beta
      and IL-6 release was significantly decreased in trauma-hemorrhage vehicle-treated
      rats. Administration of L-arginine after trauma-hemorrhage, however, improved
      splenic and peritoneal macrophage IL-1beta and IL-6 release. Moreover, the up
      regulated plasma levels of IL-6 were attenuated by L-arginine administration.
      CONCLUSION: L-Arginine administration after trauma-hemorrhage significantly
      improves the depressed macrophage function, presumably by decreasing the
      increased plasma IL-6 levels and improving organ blood flow. Early enhancement of
      the depressed constitutive nitric oxide synthase activity by provision of L
      arginine after trauma-hemorrhage, therefore, represents a novel and safe approach
      for improving the depressed immune function and decreasing plasma IL-6 levels
      under such conditions.

PMID- 9932682
TI  - Circulating postinjury neutrophils are primed for the release of proinflammatory
      cytokines.
AB  - BACKGROUND: Postinjury neutrophil (PMN) priming identifies the injured patient at
      risk for the subsequent development of multiple organ failure (MOF). PMN priming
      has previously been shown to cause enhanced release of proteases and superoxide.
      PMNs, however, are a rich source of proinflammatory cytokines, such as
      interleukin (IL)-8 and tumor necrosis factor (TNF), which have been implicated in
      the development of MOF. PMNs also make IL-1ra, which is an anti-inflammatory
      cytokine that inhibits IL-1. It is our hypothesis that postinjury PMNs are primed
      for increased stimulated release of the proinflammatory cytokines IL-8 and TNF
      but not the anti-inflammatory cytokine IL-1ra. METHODS: Twelve trauma patients
      with a mean Injury Severity Score of 24 (+/-4.6) and 10 elective surgical
      patients were studied. Postinjury PMNs were isolated from blood obtained at
      presentation (within 2 hours after injury) and 24 hours after trauma. PMNs from
      elective surgical patients were obtained preoperatively, immediately
      postoperatively, and at 24 hours. The PMNs were stimulated with platelet
      activating factor (200 nM)/N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L)
      or lipopolysaccharide (100 ng/mL) incubated for 24 hours in RPMI-1640, and
      release of IL-8, TNF, and IL-1ra were measured. RESULTS: Postinjury PMNs were
      primed for both platelet-activating factor/N-formyl-methionyl-leucyl
      phenylalanine-stimulated and lipopolysaccharide-stimulated IL-8 and TNF release
      at 2 hours after injury (fourfold increase of IL-8 release and fivefold increase
      of TNF release), whereas elective surgical patients demonstrated no priming. In
      contrast, postinjury patients were not primed for increased release of the
      counterinflammatory cytokine IL-1ra, suggesting a specific postinjury up
      regulation of IL-8 and TNF. CONCLUSION: After injury, PMNs are primed for
      proinflammatory cytokine release in addition to superoxide and elastase. This
      augmented release of IL-8 and TNF may be involved in the subsequent development
      of organ dysfunction and ultimately MOF.

PMID- 9932683
TI  - Effect of dry fibrin sealant dressings versus gauze packing on blood loss in
      grade V liver injuries in resuscitated swine.
AB  - BACKGROUND: We conducted this study to determine whether the dry fibrin sealant
      dressing (DFSD) would stop bleeding from a grade V liver injury and to evaluate
      the effects of leaving the absorbable DFSD in survival animals. METHODS: Twenty
      four swine (40+/-3.0 kg) received a uniform grade V liver injury and were
      randomized to one of four 1-hour treatment groups: (1) gauze packing, (2) DFSD,
      (3) immunoglobulin G placebo dressing, and (4) no treatment. All animals were
      resuscitated with lactated Ringer's solution. Total blood loss (TBL), mean
      arterial pressure, resuscitation volume, and laboratory data were monitored for 1
      hour after injury. Four swine were treated with the DFSD after grade V injury and
      allowed to survive for 7 or 14 days. RESULTS: The TBL was 1,104+/-264 mL (mean +/
      SEM), 544+/-104 mL, 4,223+/-1,555 mL, and 6,026+/-1,020 mL for groups 1, 2, 3,
      and 4 respectively. TBL in DFSD animals was less than that in animals treated
      with gauze packing (p = 0.06). Grade V injuries were uniform among the 1-hour
      groups, and no evidence of intrahepatic abscess, unusual adhesions, or hepatic
      vein, vena caval, or pulmonary thromboses were noted in the long-term survival
      animals. CONCLUSION: In this model of grade V liver injury, blood loss with the
      DFSD was 51% of that observed with standard gauze packing (not statistically
      different). Initial survival data revealed no complications attributable to the
      fibrin dressing. DFSD may provide simple, rapid, and definitive hemorrhage
      control in life-threatening liver injuries without the need for reoperation.

PMID- 9932684
TI  - Long-term outcome in children with fractures of the proximal femur after high
      energy trauma.
AB  - BACKGROUND: Fractures of the femoral head and neck in children have a risk of
      severe complications, especially femoral head necrosis. We performed a long-term
      follow-up study of patients treated at our institution. METHODS: Patients were
      reexamined at least 3 years after trauma and were included if they were younger
      than 17 years old at the time of injury, if there was no history of previous
      fracture, and if there was no history of underlying bone disease. Fractures were
      classified according to Delbet, and outcome was graded according to Ratliff.
      Anterior capsulotomy was not performed, and stabilization devices were placed
      short of the epiphysis except for type I fractures. RESULTS: Of 32 patients, 28
      were reexamined. Among these patients, the mean age at the time of injury was
      11.8 years and the mean follow-up time was 11.1 years (range, 3-21 years). There
      were 3 patients with type I fractures, 8 patients with type II fractures, 12
      patients with type III fractures, and 5 patients with type IV fractures. Thirteen
      patients had Injury Severity Scores > 18. At last follow-up, 20 patients
      presented with good function, 5 with fair outcome, and 3 with poor results; all
      of the latter suffered type I fractures. Eighteen patients had no restrictions in
      activities of daily living or during sports activities. In six other patients,
      the inability to participate in sports was attributable to head trauma,
      amputation, or peripheral neurologic damage. CONCLUSION: We found favorable long
      term outcome in type II to type IV fractures. In these patients, restrictions of
      function were usually caused by other associated injuries. All patients with type
      I fractures presented with poor outcome secondary to their proximal femoral
      fractures, and not because of other associated injuries. Type I fractures during
      childhood and adolescence represent an unsolved problem.

PMID- 9932685
TI  - Predicting the need for thoracoscopic evacuation of residual traumatic
      hemothorax: chest radiograph is insufficient.
AB  - BACKGROUND: The early removal of large residual posttraumatic hemothorax by
      videothoracoscopy is increasingly used to avoid the late sequelae of trapped lung
      and empyema. Plain chest radiography (CXR) is the tool most frequently used to
      select such cases for operation. Our recent experience has demonstrated that what
      appears to be a large retained hemothorax on CXR may turn out to be
      intrapulmonary or extrapleural conditions not amenable to thoracoscopic removal.
      Our objective was to evaluate the accuracy of CXR in detecting significant
      residual hemothorax and compare its clinical value to thoracic computed
      tomography (CT) when used to select patients for thoracoscopic evacuation.
      METHODS: All patients requiring tube thoracostomy for traumatic hemothorax were
      prospectively evaluated during a 22-month period (n = 703). Patients who, on the
      second day after admission, demonstrated opacification on CXR involving more than
      the costophrenic angle were evaluated by thoracic computed tomography for the
      presence of undrained fluid. Second-day CXR (CXR2) results were compared with the
      CT findings. Incorrect interpretation was defined as a difference of more than
      300 mL between the two readings. All CXR2 and CT results were reviewed in the
      same fashion by a radiologist blinded to the surgeon's interpretations. Data on
      injury mechanism, hemodynamic status, laboratory values, interventions, and
      outcome were collected prospectively. RESULTS: Fifty-eight patients had
      clinically significant opacifications on CXR2. The surgeon's and radiologist's
      CXR2 interpretations were incorrect in 48 and 47% of the cases, respectively. The
      CT interpretations by the two specialists were in agreement in 97% of the cases.
      Management that would have been instituted on the basis of CXR2 findings was
      changed in 18 cases (31%). Twelve patients (21%) required early thoracoscopic
      evacuation of undrained collections. There was good correlation between the CT
      estimation and the thoracoscopically retrieved amount of blood. CONCLUSION:
      Although CXR is useful as a screening tool, it cannot be used to reliably select
      patients for surgical evacuation of retained traumatic hemothorax. Decision
      making should be based on thoracic CT findings.

PMID- 9932686
TI  - Using queueing theory to determine operating room staffing needs.
AB  - BACKGROUND: To meet American College of Surgeons criteria, Level I and II trauma
      centers are required to have in-house operating room (OR) staff 24 hours per day.
      According to the number of emergency cases occurring, hospitals may have varying
      needs for OR staffing during the night shift. Queueing theory, the analysis of
      historic data to provide optimal service while minimizing waiting, is an
      objective method of determining staffing needs during any time period. This study
      was done to determine the need to activate a backup OR team during the night
      shift at a designated, verified Level II trauma center. METHODS: The basic
      queueing theory formula for a single-phase, single-channel system was applied to
      patients needing the services of the OR. The mean arrival rate was determined by
      dividing the number of actual cases by 2,920 hours in a year (8 hours per night x
      365). The mean service rate is determined by averaging the length of the actual
      cases during the period studied. Using the mean arrival rate and the mean service
      rate, the probability of two or more patients needing the OR at the same time was
      determined. This probability was used to reflect the likelihood of needing to
      activate the backup OR team. Simulation was then used to calculate the same
      probability and validate the results obtained from the queueing model. RESULTS:
      All OR cases (n = 62) beginning after 11 PM and before 7 AM from July 1, 1996,
      through June 30, 1997, were analyzed. During the study period, the average
      arrival rate (A) was one patient every 5.9 days (0.0212 patient every hour), with
      an average service rate (mu) of 80.79 minutes per patient (0.7427 patients per
      hour). According to queueing theory, lambda = 0.0212 patients per hour, mu =
      0.7427 patients per hour, lambda/mu = 0.0285, the probability of no patients
      being in the system (P0) = 0.9714, P1 = 0.0278, P> or =2 = 1 - (0.0278 + 0.9714)
      = 0.0008. The probability of two or more cases occurring simultaneously on the
      night shift is less than 0.1%. CONCLUSION: In our institution, activation of a
      second OR team is unnecessary when the first team is busy with a case on the
      night shift because the likelihood of two cases occurring concurrently is less
      than one in a thousand. Queueing theory can be a valuable tool to use in
      determining the staffing needs of many hospital departments. Trauma centers
      should apply this mathematical model in optimizing the use of their operational
      resource.

PMID- 9932687
TI  - Comparison of performance of interns completing the old (1993) and new
      interactive (1997) Advanced Trauma Life Support courses.
AB  - BACKGROUND: The 1997 edition of the Advanced Trauma Life Support (ATLS) course
      emphasized interactivity as its major change. The impact of this change is
      assessed in this study. METHODS: We compared two matched groups of 16 interns
      completing either the old (group I) or new (group II) ATLS course. Cognitive
      skills (40 standard ATLS questions plus 10 additional questions on airway and
      shock) and clinical trauma management skills (four trauma objective structured
      clinical examinations [OSCEs] on simulated trauma patients) were tested. OSCE
      station scores (standardized to a maximum of 20), priority scores (graded 1-7),
      organized approach global passing grades (graded 1-5), and initial assessment
      test station scores (graded 1-5) were compared. RESULTS: Using ATLS criteria,
      three interns failed in each group. Post-ATLS examination question scores were
      similar (84.5+/-6.9 for group I, 85.9+/-7.1 for group II); scores for the airway
      and shock questions were higher but not different between the two groups. The
      four OSCE station mean scores varied between 13.9+/-2.0 and 15.4+/-2.1 for group
      I and were higher (p < 0.05) for group II (17.9+/-1.6 to 19.1+/-1.0). Priority
      scores were similar (group I, 6.3+/-1.1; group II, 6.4+/-1.2), but approach
      scores (3.9+/-0.1 for group I and 4.9+/-0.8 for group II) were lower in group I,
      as were the initial assessment test scores (2.9+/-0.2 for group I and 4.9+/-0.8
      for group II). There were 8 honors grades in group I and 40 (p < 0.05) in group
      II. Interactive teaching, adult education principles, opportunities for
      discussion, provision of feedback, and stimulation of self-learning were rated
      more highly in the new course. CONCLUSION: Using standard ATLS pass criteria,
      performance after the new and old ATLS courses was similar. Superior performances
      were measured using OSCE methodology for clinical trauma management skills after
      the new compared with the old ATLS course in this population of interns.

PMID- 9932688
TI  - Management of blunt splenic trauma in patients older than 55 years. Southern
      Connecticut Regional Trauma Quality Assurance Committee.
AB  - BACKGROUND: Many experts have suggested that blunt splenic trauma in patients
      older than 55 years should not be managed by observation because of supposed
      increased fragility of the spleen and decreased physiologic reserve in elderly
      patients. We sought to determine the outcome of nonoperative management of blunt
      splenic trauma in patients older than 55 years. METHODS: For the years 1994
      through 1996, data for patients with splenic injury older than 55 years from
      seven trauma centers in a single state were reviewed. RESULTS: Blunt splenic
      trauma occurred in 41 patients older than 55 years. Eight patients were excluded
      from further analysis because of death from massive associated injuries within 24
      hours of admission. The remaining 33 patients (mean age, 72+/-10 years) were
      divided into two groups: immediate exploration (10 patients) and observation (23
      patients). Observation of blunt splenic injury failed in 4 of 23 patients (17%).
      No patient deaths were related to the method of management of the splenic injury.
      CONCLUSIONS: Observation of the elderly patient with blunt splenic trauma has an
      acceptable failure rate of 17%.

PMID- 9932689
TI  - Microvascular response to compartment syndrome-like external pressure elevation:
      an in vivo fluorescence microscopic study in the hamster striated muscle.
AB  - OBJECTIVE: To quantitatively assess the nature and the magnitude of the
      microvascular response of striated muscle tissue upon elevation of external
      pressure, as in compartment syndrome. METHODS: Using the skinfold chamber model
      in Syrian golden hamsters and intravital fluorescence microscopy, we studied the
      individual response of the different segments of the microcirculation, i.e., the
      arterioles, capillaries, and postcapillary venules, in terms of vasomotor control
      (change of vessel diameter) and cessation of blood flow upon defined changes in
      external tissue pressure. RESULTS: The unique findings of our study are that (1)
      arteriolar flow ceased at mean external pressures of 25.6+/-2.4, 28.3+/-2.8,
      34.5+/-4.6, and 44.4+/-6.8 mm Hg in vessels with diameters of less than 20, 20 to
      40, 40 to 60, and greater than 60 microm, respectively, without signs of spasm or
      collapse even at a pressure maximum of 70 mm Hg, whereas (2) in venules the
      increase of external pressure was associated with a diameter reduction ranging
      from 5 to 25% with cessation of blood flow at mean external pressures between 27
      and 33 mm Hg. Blood flow ceased in 50% of the muscle capillaries already at an
      external pressure of 12 mm Hg. Thus, at distinct external pressure levels venous
      and capillary blood flow ceased, but arterioles were still capable of carrying
      flow, which was directed along arteriolo-arteriolar "thoroughfare" channels. To
      restart blood flow, external pressure had to be decreased by 9, 11, 15, and 17 mm
      Hg in arterioles with diameters of less than 20, 20 to 40, 40 to 60, and greater
      than 60 microm, and by approximately 9 mm Hg in venules regardless of vessel
      diameter. Capillary blood flow was found to be restored at a mean reduction of
      external tissue pressure of approximately 4 mm Hg. CONCLUSION: Our study
      disproves the critical closing theory but complies-in particular because of the
      supposed constriction-induced increase of venular resistance-with the hypothesis
      of reduced arteriovenous pressure gradients as the cause of flow cessation in
      compartment syndrome. The necessity of a substantially increased perfusion
      pressure gradient to restart blood flow in arterioles, capillaries, and venules
      confirms the existence of yield stress in these microvessels. The high
      susceptibility of capillaries to elevated external pressure indicates the
      necessity of early fasciotomy to restore impaired nutritive circulation in cases
      of compartment syndrome.

PMID- 9932690
TI  - Management of femoral diaphyseal infected nonunion with antibiotic beads local
      therapy, external skeletal fixation, and staged bone grafting.
AB  - BACKGROUND: Fifteen patients with femoral shaft fractures complicated by infected
      nonunions were treated with a two-stage protocol. METHODS: In the first stage,
      radical debridement was performed along with antibiotic bead chains local therapy
      and external skeletal fixation. In the second stage, the debrided nonunion site
      was repaired with bone grafting and the external skeletal fixator was used until
      bony union was achieved. The time between the first and second stages of
      treatment was 2 to 6 weeks. The debrided bone defects ranged from 0.5 to 15 cm.
      Autogenous iliac cancellous bone grafting was performed in 11 patients, and
      microvascularized osteoseptocutaneous fibular transfer was performed in 4
      patients. RESULTS: Wound healing and bone union were achieved in all 15 cases.
      The duration of external fixation of these patients ranged from 7 to 15 months,
      with an average of 9 months. Minor pin-track infection was seen in seven
      patients. Postoperative infection after the second-stage bone grafting occurred
      in three patients. These three infections were arrested by limited debridement
      along with 2 to 4 weeks of parenteral antibiotic therapy. In one case, stress
      fracture occurred at 11 months after microvascularized fibular transfer; this was
      managed with another 5 months of external skeletal fixation. With an aggressive
      physical therapy program, 10 patients achieved nearly full range of knee motion
      and 5 patients had relevant knee flexion deficits. The follow-up averaged 58
      months (range, 40-76 months); no recurrence of osteomyelitis was observed even at
      76 months. CONCLUSION: We have found that our two-stage treatment with antibiotic
      beads local therapy, definitive external skeletal fixation, and staged bone
      grafting is an acceptable treatment protocol for the management of femoral
      diaphyseal infected nonunion. It results in rapid recovery from osteomyelitis and
      a predictable recovery from nonunion.

PMID- 9932691
TI  - Ankylosed hips caused by heterotopic ossification after traumatic brain injury: a
      difficult problem.
AB  - BACKGROUND: Heterotopic ossifications develop around major joints after severe
      traumatic brain injury and decrease the range of motion of the joints. METHODS:
      From 1982 to 1994, we operated on 22 ankylosed hips caused by heterotopic
      ossifications after traumatic brain injury. Our 15 patients had been hospitalized
      in the intensive care unit for a period of 8 to 57 days. Their preoperative
      neurologic status was evaluated precisely. Special interest was given also to the
      accurate estimation of the extent and location of the ectopic bone by using x
      rays and computed tomography, as well as to the maturity of the bone by using
      Tc99 bone scan and measurements of serum alkaline phosphatase levels.
      Intraoperatively, we resected as much ectopic bone as was needed to achieve
      functional range of motion in the hip. Postoperatively, all the patients were
      administered 100 mg of indomethacin (suppository) per day for a month,
      antibiotics, and anticoagulants. They were also exposed to 1,000 cGy of radiation
      in two equal doses. RESULTS: We achieved a least functional range of motion in 15
      of 22 hips. Of the seven hips with poor results, six cases were attributable to
      the uncontrolled neurologic syndrome and only one poor result was attributable to
      severe heterotopic ossification recurrence. Wound complications did occur.
      CONCLUSION: Ankylosed hips caused by heterotopic ossifications after traumatic
      brain injury are a difficult problem to manage. Accurate evaluation of the
      preoperative neurologic status is essential for the desired final outcome and the
      treatment options.

PMID- 9932692
TI  - Bone healing of tibial lengthening is delayed by cigarette smoking: study of bone
      mineral density and torsional strength on rabbits.
AB  - OBJECTIVE: We investigated the effect of intermittent cigarette smoke inhalation
      on the bone healing of tibial lengthening in rabbits. METHODS: Twelve male
      rabbits were divided into two groups of six animals each. The first group
      underwent intermittent cigarette smoke inhalation, and the second group did not
      undergo intermittent cigarette smoke inhalation. Each animal's right tibia was
      lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density
      (BMD) study was performed for all of the animals 1 day before operation and 3, 4,
      5, and 6 weeks after operation. All of the animals were killed 6 weeks
      postoperatively for biomechanical testing. RESULTS: By using the preoperative BMD
      as an internal control, we found that the BMD of the smoke-inhalation group was
      decreased significantly compared with the non-smoke-inhalation group. The mean
      %BMD at 3, 4, 5, and 6 weeks were 49.9%, 61.2%, 65.9%, and 71.0%, respectively,
      in the smoke-inhalation group, whereas the mean %BMD were 54.9%, 71.8%, 76.4%,
      and 82.0%, respectively, in the non-smoke-inhalation group (two-tailed t test, p
      > 0.05, p < 0.01, p < 0.01 and p < 0.01 at 3, 4, 5, and 6 weeks, respectively).
      By using the contralateral nonoperated tibia as internal control, we found that
      torsional strength of the smoke-inhalation group was decreased significantly
      compared with the non-smoke-inhalation group. The mean percentage of maximal
      torque was 63.8% in the smoke-inhalation group, whereas the mean percentage of
      maximal torque was 77.1% in the non-smoke-inhalation group (two tailed t test, p
      < 0.01). CONCLUSION: This study suggests that cigarette smoking delays the
      mineralization during the bone healing process of distraction osteogenesis and,
      thus, decreases the mechanical strength of the regenerating bone.

PMID- 9932693
TI  - Seventy cases of injuries of the small intestine caused by blunt abdominal
      trauma: a retrospective study from 1970 to 1994.
AB  - BACKGROUND: Injuries of the hollow viscera are far less common in blunt abdominal
      trauma than in penetrating abdominal trauma. This article is a 25-year
      retrospective study of 70 patients with injuries of the small intestine caused by
      blunt trauma. All patients were treated surgically at the trauma hospital
      (Unfallkrankenhaus) in Graz. In our series, blunt abdominal trauma causing hollow
      viscus injuries occurred in conjunction with multiple trauma in 68.8% of cases.
      The overall mortality rate was 25.7%. METHODS: The following methods were used
      for evaluating the intestinal injury: detailed history of the accident and
      examination of the patients (e.g., transverse abdominal bruise) diagnostic
      peritoneal lavage before 1984, abdominal sonography since 1984, computed
      tomography, and laboratory tests. RESULTS: Prognosis and results depended partly
      on the general condition of the patient, as well as the timeliness of diagnosis
      and surgical management of the small bowel injury. Delays in diagnosis were
      common because of the overall condition of the patient, as well as the difficulty
      in establishing a definitive diagnosis by using current radiologic and serologic
      modalities. CONCLUSION: It should be stated that the high mortality of small
      bowel injuries after blunt abdominal trauma justifies an aggressive approach to
      diagnosis and surgical treatment of these injuries. This article focuses on
      injury mechanisms and current concepts in diagnosis and the therapy of small
      intestine lacerations in blunt abdominal trauma.

PMID- 9932694
TI  - Outcome assessment of physiologic and clinical predictors of survival in patients
      after traumatic injury with a trauma score less than 5.
AB  - OBJECTIVE: To define those physiologic and clinical variables that have a
      positive or negative predictive value in discriminating survivors from
      nonsurvivors with traumatic injuries and a Trauma Score of 5 or less. METHODS: A
      retrospective review of 2,622 trauma patients transported by an air medical
      service from the scene of injury to a Level I trauma center was performed.
      Demographic, physiologic, and clinical variables were evaluated. RESULTS: One
      hundred thirty-six patients were studied; 14 patients survived trauma
      resuscitation. Survivors had statistically significant improvement in the Glasgow
      Coma Scale from the field to arrival in the emergency room. Revised Trauma Score,
      probability of survival, pulse, respiratory rate, cardiac rhythm, central nervous
      system activity, and signs of life were statistically more favorable in
      survivors. CONCLUSION: In patients who survived to discharge, signs of central
      nervous system activity in the field was a positive predictor of survival, and
      severe head injury served as a negative predictor of survival.

PMID- 9932695
TI  - Bronchoscopic lavage with perfluorocarbon decreases postprocedure hypoxemia in an
      ovine model of smoke inhalation.
AB  - OBJECTIVE: Bronchoscopy and lavage are used to confirm diagnosis and can be
      therapeutic in patients suffering inhalation injury. Lavage is traditionally
      performed using saline, which is unfortunately associated with profound transient
      hypoxemia. Perfluorocarbons, having a high gas solubility for oxygen and carbon
      dioxide, increase oxygenation when instilled into the airway. We hypothesized
      that the use of perfluorocarbons for bronchoscopic lavage would attenuate this
      transient hypoxemia. METHODS: Sheep were prepared for chronic study. They were
      insufflated with cotton smoke and then randomized to receive a lavage with 200 mL
      of perfluorocarbon or saline at 2, 6, 12, and 24 hours after injury. RESULTS: All
      animals had a steady and significant decline in their pre- to post-PaO2/FiO2
      (P/F) ratio. At 2, 6, and 12 hours, the saline lavage group had a significant
      decrease in their P/F ratio (485+/-32 to 212+/-37 mm Hg, 439+/-22 to 170+/-40 mm
      Hg, and 381+/-48 to 184+/-59 mm Hg). This decrease in P/F ratio was not observed
      in the perfluorocarbon group (474+/-19 to 459+/-29 mm Hg, 424+/-32 to 387+/-43 mm
      Hg, and 366+/-50 to 357+/-67 mm Hg). CONCLUSION: These findings indicate that
      perfluorocarbons attenuate the transient hypoxemia associated with saline
      bronchoscopic lavage and thus may be considered safer for patients with acute
      lung injury.

PMID- 9932696
TI  - Inhibiteur de rejet de greffe alpha2-macroglobulin in burn injury: a suppressive
      activity on complement.
AB  - A subform of alpha2-macroglobulin, (inhibiteur de rejet de greffe (IRG), present
      at a low rate in healthy rat, increased with rate-related suppressive activity on
      complement during inflammatory processes. In human serum, a molecule with such
      properties was described. Serum and blister IRG from burn patients belonging to a
      selected population was purified under gentle conditions. Serum IRG increased
      quickly within the first day after hospitalization and continued to increase
      until day 6. Although absent in whole serum, the rate-related activity of IRG
      varied according to the surface area and the degree of burns. A rate-related
      activity was also revealed in whole blister fluid and in purified blister IRG. We
      report a new site and a new suppressive activity of IRG in its native form from
      serum and blister fluid during inflammatory processes of burned patients. The
      suppressive activity of IRG on complement is discussed, and it appears to play a
      role in the development of inflammatory processes.

PMID- 9932697
TI  - Acute renal dysfunction in severely burned adults.
AB  - BACKGROUND: Factors contributing to mortality in burned children with acute renal
      failure have been identified; however, they have not been identified in thermally
      injured adults. METHODS: The records of 1,404 acutely burned adults admitted to
      the Blocker Burn Unit were reviewed. Seventy-six patients with acute renal
      dysfunction and burns covering more than 30% of their total body surface area
      with a full-thickness component greater than 10% total body surface area were
      identified. These patients were divided into those admitted from 1981 through
      1989 (n = 35) and those admitted from 1990 to 1998 (n = 41). RESULTS: No
      significant differences could be shown in the incidence of acute renal
      dysfunction (5.4 vs. 5.1%) or mortality (88 vs. 87%) for the two time periods,
      respectively. Sixty-seven percent of the survivors were younger than 40 years of
      age, compared with only 25% of nonsurvivors (p < 0.02); sepsis was identified in
      44 and 96% of survivors and nonsurvivors, respectively (p < 0.001). Fluid
      resuscitation was delayed in survivors by 1.7+/-1.0 hours compared with 4.4+/-2.1
      hours in nonsurvivors (p < 0.001). CONCLUSION: early fluid resuscitation and the
      prevention of sepsis may reduce the incidence of acute renal dysfunction and
      mortality in burned adults.

PMID- 9932698
TI  - Sublethal hemorrhage blunts the inflammatory cytokine response to endotoxin in a
      rat model.
AB  - BACKGROUND: Tolerance to lipopolysaccharide (LPS) induced by previous hemorrhage
      in mice is associated with a blunted interleukin 1 (IL-1) response, suggesting
      down-regulation of the cytokine cascade as a possible protective mechanism. This
      study was undertaken to determine whether prehemorrhage induces attenuation of
      the cytokine response to sepsis beyond IL-1 in a rat model and whether this
      response occurs at the level of gene transcription. METHODS: Sprague-Dawley rats
      underwent sublethal hemorrhage, lethal intraperitoneal endotoxin, or sublethal
      hemorrhage with delayed lethal endotoxin. Animals were killed 12 hours after LPS
      injection or 24 hours after hemorrhage. IL-1 and tumor necrosis factor (TNF) mRNA
      levels were determined on total splenic RNA using reverse-transcriptase
      polymerase chain reaction, and serum cytokine levels were determined using enzyme
      linked immunosorbent assay. RESULTS: Animals that received LPS alone mounted an
      IL-1 and TNF response (RNA and protein) much higher than animals subjected to
      hemorrhage alone. TNF and IL-1 gene expression and protein levels in
      prehemorrhaged animals that received LPS, however, were significantly lower than
      those of animals that received LPS alone. CONCLUSION: Hemorrhage induces early IL
      1 and TNF gene expression, which blunts their subsequent expected increase after
      endotoxic challenge. These findings validate previously documented immune
      modulated protective effects of the first insult in a two-hit model.

PMID- 9932699
TI  - Ureteric injuries: diagnosis, management, and outcome.
AB  - OBJECTIVES: To define the current causes and the optimal methods of early
      diagnosis and management of ureteric injuries, both iatrogenic (excluding
      endourologic) and traumatic, and to determine the outcome of these injuries and
      which identifiable factors affect this outcome. METHODS: A retrospective analysis
      was performed of all the 35 patients who sustained 40 ureteric injuries over a 5
      year period (1991-1996). The methods used for diagnosis and management were
      reviewed. The outcome was assessed in terms of preservation of renal function.
      RESULTS: The study group was composed of 28 patients with 32 iatrogenic injuries
      and 7 patients with 8 injuries caused by external trauma. Gynecologic procedures
      accounted for 63% (20 of 32) of the iatrogenic injuries, whereas motor vehicle
      crashes accounted for 75% of the external injuries (6 of 8 injuries). The
      successful diagnostic rate for direct inspection (intraoperatively), intravenous
      urogram, retrograde pyelogram, and anterograde pyelogram were 33% for the former
      two and 100% for the latter two. Treatment consisted of primary open repair in 26
      cases, a staged procedure in 7 cases, and endoscopic stenting in 5 cases. Of 36
      cases with follow-up, complications developed in 9 cases (25%), 7 cases of which
      were corrected surgically. Overall incidence of nephrectomy was 8%, and the
      factors that seemed to affect the outcome adversely were pediatric age (< or =12
      years), injury to upper ureter, delay in recognition, the presence of a urinoma,
      and/or associated organ injury. CONCLUSION: Iatrogenic trauma is the leading
      cause of ureteric injuries. The single controllable factor adversely affecting
      the outcome of this rather uncommon injury seems to be delayed diagnosis. Wound
      inspection and intravenous urogram are not reliable for early and accurate
      diagnosis, and a retrograde pyelogram or an anterograde pyelogram may be needed.
      Uncontrollable factors adversely affecting the outcome include young age, injury
      to upper ureter, and associated injuries all seen in association with external
      trauma rather than iatrogenic injuries.

PMID- 9932700
TI  - Assessment of executive function in patients with mild traumatic brain injury.
AB  - BACKGROUND: The nature of functional deficit after mild traumatic brain injury
      (TBI) defined by Glasgow Coma Score of 13-15 is not fully described. This study
      explored the sensitivity of several neuropsychological tests to identify sequelae
      of mild traumatic brain injury (TBI). METHODS: Eleven adult patients with mild
      TBI admitted to a Level 1 trauma center were studied. The battery of tests
      included the Wechsler Intelligence Scale for Children -Revised: Mazes Subtest,
      Trails A and B, the Boston Naming Test, The Multilingual Aphasia Examination:
      Controlled Oral Word Association Test, and the Paced Auditory Serial Addition
      Task. RESULTS: Control subjects performed significantly better than patients with
      mild TBI on Trails A and B, the Controlled Oral Word Association Test, and Paced
      Auditory Serial Addition Task (subtests 2-4). No significant differences in
      performances between patients and controls was found for the Wechsler
      Intelligence Scale for Children -Revised: Mazes Subtest, Boston Naming Test, and
      Paced Auditory Serial Addition Task Subtest 1. CONCLUSION: The results suggest
      that tests of specific frontal lobe executive functions are valuable in
      diagnosing and monitoring recovery from mild TBI.

PMID- 9932701
TI  - Traumatic rupture of hydatid cysts: a 12-year experience from an endemic region.
AB  - BACKGROUND: Trauma as a cause of hydatid cyst rupture leads to various clinical
      sequelae. However, extensive data in the current literature regarding clinical
      presentation and management of such patients are lacking. METHODS: This article
      is a retrospective review of 16 patients with traumatic rupture of hydatid cysts
      treated at a university hospital in an endemic area. RESULTS: Falls (44%) were
      the most common cause of trauma. The ruptured cysts were located in the liver in
      13 patients (81%), in the spleen in 2 patients, and in the lung in 1 patient.
      Computerized tomography had a sensitivity of 100% in demonstrating cyst rupture;
      whereas, ultrasonography had a sensitivity of 85%. Ten patients (62%) had rupture
      into the peritoneal cavity and 5 patients (31%) into the biliary tree. Five (31%)
      of the cysts were infected. Surgical procedures included introflexion (five
      patients), pericystectomy-choledochoduodenostomy (three patients), external
      drainage-choledochoduodenostomy (two patients), unroofing-external drainage (two
      patients), splenectomy (two patients), unroofing (one patient), and right
      hepatectomy (one patient). Mean length of hospitalization was 15.9 days (range, 5
      61 days). One patient (6%) died, and eight patients (50%) developed
      complications. Nine patients (56%) were followed-up for an average of 30 months
      (range, 3-72 months), and there was no recurrence. CONCLUSION: Computed
      tomography is currently the most sensitive diagnostic tool for demonstrating
      hydatid cyst rupture. The surgical options vary depending on intraoperative
      findings. Allergic reactions and recurrence as a result of intraperitoneal
      spillage are not as common as once believed. Biliary rupture is associated with
      an increased rate of wound infection.

PMID- 9932702
TI  - Compliance with prehospital triage protocols for major trauma patients.
AB  - BACKGROUND: The extent to which severely injured patients receive definitive care
      at trauma centers is determined by the accuracy of prehospital major trauma
      criteria in predicting severe injuries and by the level of compliance with these
      triage instructions by prehospital providers. This study was conducted to
      evaluate the level of compliance with triage criteria in an established trauma
      system. METHODS: The study involved a retrospective analysis of the 1995 Maryland
      statewide prehospital ambulance data. Prehospital providers in Maryland are
      instructed to consider transporting patients meeting any of the three
      nonexclusive major trauma criteria-physiology, injury, and mechanism-to
      designated trauma centers. Compliance with these criteria was defined as the
      proportion of patients transported to designated trauma centers among those
      meeting prehospital triage criteria as documented on the ambulance trip report.
      Special emphasis was placed on differences in the levels of compliance by age of
      the trauma patients. RESULTS: A total of 32,950 transports were analyzed.
      Patients meeting injury criteria were most likely to be transported to trauma
      centers (86%), followed by those meeting mechanism criteria (46%), and physiology
      criteria (34%). When the level of compliance was stratified by age, there was no
      age difference in the level of compliance for patients meeting injury criteria
      (90.5% for patients aged 0-54 years vs. 88.7% for patients aged 55+ years; p =
      0.197). For older patients meeting physiology criteria only or for those meeting
      mechanism criteria only, however, compliance was differentially low. For patients
      meeting physiology criteria only, the compliance was 40.3% for patients aged 0 to
      54 years and 23.9% for patients aged 55 years and older (p = 0.0001); for
      patients meeting mechanism criteria only, compliance was 47.0% for patients aged
      0 to 54 years and 39.7% for patients aged 55+ years (p = 0.002). CONCLUSION: The
      majority of patients meeting prehospital major trauma criteria were transported
      to designated trauma centers. Patients meeting only physiology criteria, however,
      were much less likely to be transported to trauma centers, and there was a
      differentially low compliance for elderly trauma patients meeting physiology
      criteria alone. The causes and consequences of lower compliance with triage
      instructions for the elderly population deserve further investigation.

PMID- 9932703
TI  - Prehospital blood transfusion in prolonged evacuation.
AB  - BACKGROUND: Prehospital blood transfusion for hemorrhaging trauma patients has
      been used infrequently and is controversial. Currently, there is no satisfactory
      nonsanguineous fluid therapy for use during prolonged transport, such as in
      military or rural trauma. METHODS: We retrospectively reviewed prehospital data
      and hospital charts of all trauma patients in Israel who had received prehospital
      blood transfusion during a period of 30 months. RESULTS: Forty patients received
      60 U of Rh-positive type O packed red blood cells. Mean time from injury to
      hospital admission was 120 minutes. Twenty-one of 31 patients admitted to the
      hospital alive (68%) received additional blood transfusions during the initial
      resuscitation phase, justifying the prehospital transfusion. Of nine documented
      admissions with hemoglobin of less than 7 g/dL, one patient died of
      exsanguination. There was one case of a minor adverse reaction that could be
      attributed to prehospital transfusion. CONCLUSION: Prehospital blood transfusion
      is justified in certain trauma patients, especially when long prehospital
      transport is required. Blood may be safely maintained and used by physicians with
      little experience in care of major trauma.

PMID- 9932704
TI  - The role of xenon-enhanced computed tomography in the management of a traumatic
      carotid-cavernous fistula: case report.

PMID- 9932705
TI  - Superselective embolization of a traumatic intrasplenic arteriovenous fistula.

PMID- 9932706
TI  - Unusual pseudoaneurysm of an axillofemoral bypass caused by seat belt trauma:
      case report.

PMID- 9932707
TI  - Blunt vena azygos trauma: report of a case and review of world literature.

PMID- 9932708
TI  - Cardiac arrest caused by reperfusion injury after lumbar paraspinal compartment
      syndrome.

PMID- 9932709
TI  - Blockade of accumbens 5-HT3 receptor down-regulation by ondansetron administered
      during continuous cocaine administration.
AB  - The present experiment examined whether ondansetron, co-administered with
      continuous cocaine, would block the down regulation of accumbens 5-HT3 receptors.
      Rats were exposed to a 14-day pretreatment regimen that involved the continuous
      infusion of 40 mg kg(-1) day(-1) cocaine or 0.9% saline via a subcutaneously
      implanted osmotic minipump. In addition to the continuous cocaine or saline
      administration, all subjects received daily subcutaneous (s.c.) injections of
      either vehicle or 0.1 mg kg(-1) ondansetron for the entire 14-day pretreatment
      regimen. The rats were then withdrawn from this pretreatment regimen for seven
      days, and slices from the nucleus accumbens obtained. The slices were perfused
      with 25 mM K+ in the absence and presence of 0, 12.5, 25, or 50 microM m
      Chlorophenyl-biguanide HCl (mCPBG). The efflux samples were assayed for dopamine
      content by high pressure liquid chromatography (HPLC) with electrochemical
      detection. Continuous cocaine administration significantly attenuated the ability
      of mCPBG to facilitate K+-induce dopamine overflow compared to saline control
      rats. In addition, the rats that received ondansetron and cocaine during the 14
      day pretreatment period, the ability of mCPBG to enhance K+ stimulated dopamine
      release was not significantly different from the saline control subjects. For all
      groups except the cocaine alone group, the effects of mCPBG on K+ stimulated
      dopamine release were Ca2+ dependent, suggesting that these effects are receptor
      mediated. These results suggest that continuous cocaine administration
      functionally down-regulates 5-HT3 receptors in the nucleus accumbens, and that
      this down-regulation can be blocked by chronic ondansetron administration. Hence,
      a functional down regulation of accumbens 5-HT3 receptors represents a
      significant contribution to the tolerance induced by continuous cocaine
      administration.

PMID- 9932710
TI  - Effects of accumbens m-chlorophenylbiguanide microinjections on sleep and waking
      in intact and 6-hydroxydopamine-treated rats.
AB  - Effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide (10.0-40.0
      microg), on sleep and waking were studied in control, vehicle-treated and 6
      hydroxydopamine-injected rats. Bilateral injections of m-chlorophenylbiguanide
      into the nucleus accumbens of the control and the vehicle-infused animals
      significantly increased waking and reduced slow wave sleep. Rapid eye movement
      sleep (REM sleep) remained unchanged. Pretreatment with the selective 5-HT3
      receptor antagonist, MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate)
      (0.5 mg/kg, s.c.), reversed the effects of m-chlorophenylbiguanide (10.0-20.0
      microg) on sleep and waking in the control group. Administration of the 5-HT3
      receptor agonist to the 6-hydroxydopamine-treated animals modified only slightly
      the time spent in wakefulness and slow wave sleep, while REM sleep was
      significantly and dose dependently reduced. Our findings further support the
      proposal that increase of wakefulness and reduction of slow wave sleep after
      activation of 5-HT3 receptors, is partly related to the release of endogenous
      dopamine.

PMID- 9932711
TI  - Parallel dose-response studies of the voltage-dependent Na+ channel antagonist
      BW619C89, and the voltage-dependent Ca2+ channel antagonist nimodipine, in rat
      transient focal cerebral ischaemia.
AB  - We have compared two classes of putative neuroprotectants, the voltage-dependent
      Na+ channel antagonist BW619C87 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5
      trichlorophenyl) pyrimidine], and the voltage-dependent Ca2+ channel antagonist
      nimodipine, in a rat model of transient focal cerebral ischaemia. BW619C87 (10-50
      mg/kg) or nimodipine (10-100 microg/kg) were injected intravenously 5 min before
      induction of 2 h transient focal cerebral ischaemia via intraluminal thread
      occlusion of the middle cerebral artery. BW619C87 was a potent neuroprotectant
      over the range tested, maximally reducing the volume of hemispheric ischaemic
      damage by 51% at the 50 mg/kg dose. Nimodipine maximally reduced ischaemic damage
      by 33% at the 50 microg/kg dose, although the maximal level of neuroprotection
      afforded by BW619C89 and nimodipine was not significantly different. This is the
      first study to compare these two classes of drug directly in a model of middle
      cerebral artery occlusion with reperfusion, and it supports the effectiveness of
      both as neuroprotectants.

PMID- 9932712
TI  - Type B and type C natriuretic peptide receptors modulate intraocular pressure in
      the rabbit eye.
AB  - We investigated (1) the in vivo functional significance of the type B (ANP(B))
      and type C (ANP(C)) natriuretic peptide receptors in the rabbit eye by evaluating
      the effect of intracameral administration of C-type natriuretic peptide (CNP) and
      C-ANP-(4-23) on intraocular pressure, and (2) the action of CNP on guanylate
      cyclase activity in the rabbit ciliary process membranes. Atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP) were also studied for
      comparison. We demonstrated that the natriuretic peptides decrease intraocular
      pressure and stimulate guanylate cyclase activity, CNP being the most potent. The
      duration of the effect of C-ANP-(4-23) on intraocular pressure reduction was
      almost 9-fold that of the BNP and 20-fold that of ANP and CNP effect. This ligand
      increased threefold the immunoreactive natriuretic peptides levels in aqueous
      humour. Our data demonstrate the presence of functional ANP(A) and ANP(B)
      receptors in the rabbit eye and that the ANP(C) receptor modulates the
      concentration of the natriuretic peptides in the aqueous humour.

PMID- 9932713
TI  - Vasopressin receptor antagonist OPC-31260 prevents cerebral oedema after
      subarachnoid haemorrhage.
AB  - The effects of the non-peptide vasopressin V2 receptor antagonist, 5
      dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrah ydro-1 H
      benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by
      subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced
      significant water retention after water loading, increased the brain content of
      water and Na+ and increased plasma vasopressin levels. The water retention and
      brain water and Na+ accumulation were prevented by OPC-31260 administration, but
      the plasma vasopressin levels were further enhanced by OPC-31260. These results
      demonstrate the important role of vasopressin in the development of antidiuresis
      and disturbances in brain water and electrolyte balance in response to
      subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema
      was significantly reduced following oral OPC-31260 administration. The protective
      mechanism exerted by OPC-31260 stems from its influence on renal tubular
      function: it blocks the renal vasopressin V2 receptors. These observations might
      suggest a new, effective approach to the treatment of subarachnoid haemorrhage
      induced cerebral oedema in humans.

PMID- 9932714
TI  - Activity and onset of action of reboxetine and effect of combination with
      sertraline in an animal model of depression.
AB  - The limitations of antidepressant drugs to treat depression has warranted ongoing
      research to identify pharmacological agents and strategies which offer a faster
      onset of action and greater therapeutic efficacy. Noradrenaline and serotonin are
      widely reported to be involved in the mechanism of action of antidepressants and
      the recent development of selective reuptake inhibitors of these transmitters has
      provided the opportunity to determine the effects of targeting these transmitter
      systems, alone and in combination, in an antidepressant response. The present
      study investigated the effects of reboxetine, a new antidepressant that
      selectively inhibits noradrenaline reuptake, sertraline, a selective serotonin
      reuptake inhibitor and a combination treatment composed of the two drugs in the
      olfactory bulbectomized (OB) rat model of depression. Sub-acute (2 days)
      administration of reboxetine (2.5, 5, and 10 mg/kg, i.p.) to sham-operated and OB
      rats reduced the immobility time in the forced swim test. Repeated (14 days)
      reboxetine (10 mg/kg) treatment attenuated the OB-related behavioural
      hyperactivity in the 'open-field' test. Examination of the onset of the
      antidepressant effect in the 'open-field' test demonstrated that reboxetine (10
      mg/kg), sertraline (5 mg/kg) and the combination reduced the behavioural
      hyperactivity after 14 days but not before this following 3, 7 or 10 days of
      treatment. Reduced 5-hydroxyindoleacetic acid (5-HIAA) concentrations in
      amygdaloid cortex of both sham and OB rats following sertraline and combination
      treatments are likely to be related to acute pharmacological effects on the
      reuptake of 5-hydroxytryptamine (5-HT). Attenuation of the hypothermia induced by
      8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.05 mg/kg s.c.) and clonidine
      (0.1 mg/kg s.c.) occurred in the reboxetine and sertraline combination treated
      groups following both 7 and 14 days administration indicating changes to 5-HT1A
      receptor and alpha2-adrenoceptor sensitivity. The results indicate that changes
      to 8-OH-DPAT and clonidine-induced responses occur quicker with the combination
      treatment than with either reboxetine or sertraline treatments alone.

PMID- 9932715
TI  - Competitive NMDA receptor antagonists disrupt prepulse inhibition without
      reduction of startle amplitude in a dopamine receptor-independent manner in mice.
AB  - Prepulse inhibition is thought to reflect the operation of the sensorimotor
      gating system in the brain, and is reduced in schizophrenic patients and in
      animals treated with non-competitive NMDA receptor antagonists such as
      phencyclidine and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10
      imine ((+)-MK-801). Previously, we reported that a competitive NMDA receptor
      antagonist, cis-4-phosphonomethyl-2-piperidine-carboxylate hydrochloride (CGS
      19755), also disrupts prepulse inhibition concomitantly with a marked reduction
      of startle amplitude elicited by pulse alone in rats. In the present study, the
      effect of NMDA receptor antagonists on prepulse inhibition was tested in mice. In
      addition, involvement of the dopaminergic system in CGS 19755-induced disruption
      of prepulse inhibition was examined. When CGS 19755 was subcutaneously
      administered at 40 and 80 mg/kg, prepulse inhibition was disrupted without any
      change in the startle amplitude elicited by pulse alone.
      Intracerebroventricularly administered CGS 19755 disrupted prepulse inhibition at
      dosages of 0.1 and 0.2 microg/mouse. The same dosages of R-3-(2-carboxypiperazin
      4-yl)-propyl-1-phosphonic acid (R-CPP), another competitive NMDA receptor
      antagonist, also decreased prepulse inhibition, while its less active enantiomer,
      S-CPP, did not affect prepulse inhibition at 0.2 microg/mouse (i.c.v.). A typical
      neuroleptic, haloperidol, did not significantly improve CGS 19755 (40 mg/kg s.c.)
      induced disruption of prepulse inhibition. These results suggest that the
      disruption of prepulse inhibition by CGS 19755 and R-CPP is NMDA receptor
      mediated and dopamine receptor-independent.

PMID- 9932716
TI  - An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of
      diabetic neuropathic pain.
AB  - The present study was conducted to characterize the development of tactile
      allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate
      the antinociceptive effects of systemically administered morphine and the
      adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model.
      Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels
      were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl)
      and vehicle-injected rats were examined weekly for the development of tactile
      allodynia by measuring the threshold for hind paw withdrawal using von Frey
      hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in
      approximately one-third of streptozotocin-treated rats 7 weeks after
      streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and
      this allodynia persisted for at least an additional 7 weeks. In additional
      experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent
      antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The
      adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose
      dependently attenuated tactile allodynia. Pretreatment with the opioid receptor
      antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine
      receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly
      diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The
      present study demonstrates that the potent and selective adenosine kinase
      inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile
      allodynia in this model.

PMID- 9932717
TI  - Citalopram elicits a discriminative stimulus in rats at a dose selectively
      increasing extracellular levels of serotonin vs. dopamine and noradrenaline.
AB  - Citalopram (2.5 mg/kg, i.p.) increased (+145-+180%) extracellular levels of
      serotonin (5-hydroxytryptamine, 5-HT) in the frontal cortex, nucleus accumbens
      and striatum of freely-moving rats, whereas dopamine and noradrenaline were
      unaffected. At this dose, employing a two-lever, food-reinforced, drug
      discrimination procedure, citalopram generated reliable recognition and fully (>
      80%) generalized to itself with an Effective Dose50 (ED50) of 0.1 mg/kg, s.c. Two
      further selective 5-HT reuptake inhibitors, sertraline and paroxetine, fully
      generalized with ED50s of 0.01 and 0.04 mg/kg, s.c., respectively. In contrast,
      the anxiolytic, diazepam (0.63), and the antipsychotic, clozapine (2.5), did not
      (< or = 20%) generalize. In conclusion, the selective 5-HT reuptake inhibitor,
      citalopram, elicits a pharmacologically-specific discriminative stimulus in rats
      at a dose selectively elevating extracellular concentrations of 5-HT.

PMID- 9932718
TI  - Peroxynitrite-mediated attenuation of alpha- and beta-adrenoceptor agonist
      induced vascular responses in vivo.
AB  - Peroxynitrite is produced by vascular endothelial and smooth muscle cells in
      response to inflammation, induces vascular relaxation, and alters vascular
      responses to endothelial-derived relaxing factors. The present study examined the
      changes in mean arterial pressure and hindquarter, renal, and mesenteric vascular
      resistances produced by the systemic administration of (i) the catecholamines
      epinephrine or norepinephrine, (ii) the alpha1-adrenoceptor agonist
      phenylephrine, (iii) the beta-adrenoceptor agonist isoproterenol or (iv) [Arg
      delta] vasopressin in pentobarbital-anesthetized rats prior to and following the
      systemic administration of peroxynitrite. The systemic administration of
      peroxynitrite significantly inhibited (i) epinephrine-induced pressor and renal
      and mesenteric vasoconstrictor responses, (ii) norepinephrine-induced pressor and
      hindquarter, renal, and mesenteric vasoconstrictor responses, (iii) phenylephrine
      induced hindquarter and mesenteric vasoconstrictor responses, and (iv)
      isoproterenol-induced depressor and hindquarter and renal vasodilator responses.
      In comparison, the systemic administration of peroxynitrite had no effect on
      arginine vasopressin-induced pressor or vasoconstrictor responses. These results
      demonstrate selective and consequential attenuation of the hemodynamic effects
      produced by alpha- and beta-adrenoceptor agonists, suggesting that selective
      impairment of adrenoceptors by peroxynitrite may play a critical role in the
      hemodynamic dysfunction associated with inflammatory conditions.

PMID- 9932720
TI  - Endothelial P2Y receptors induce hyperpolarisation of vascular smooth muscle by
      release of endothelium-derived hyperpolarising factor.
AB  - The effects of P2Y receptor agonists on smooth muscle membrane potential in
      isolated ring segments of rat mesenteric artery were examined by intracellular
      microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo
      oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate
      (ADPbetaS) induced endothelium-dependent membrane hyperpolarisations, which were
      abolished by a combination of the K+ channel inhibitors charybdotoxin and apamin,
      providing direct evidence that ADPbetaS releases endothelium-derived
      hyperpolarising factor (EDHF). 2-MethylthioATP and ATP, each which stimulates
      both endothelial P2Y receptors and P2X receptors on the smooth muscle cells, also
      elicited hyperpolarisation, but only after desensitisation of P2X receptors with
      alphabeta-methylATP indicating that simultaneous activation of P2X receptors may
      counteract the action of EDHF. In conclusion, activation of endothelial P2Y
      receptors induce release of EDHF.

PMID- 9932719
TI  - Cyclosporin-A reduces leukocyte accumulation and protects against myocardial
      ischaemia reperfusion injury in rats.
AB  - The present study was designed to evaluate the effect of cyclosporin A in a rat
      model of myocardial ischaemia reperfusion injury (MI/R). Anaesthetized rats were
      subjected to total occlusion (20 min) of the left main coronary artery followed
      by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R)
      were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity
      (MPO), serum creatinine phosphokinase activity (CPK), serum tumor necrosis factor
      (TNF-alpha), cardiac mRNA for TNF-alpha, cardiac intercellular adhesion molecule
      1 (ICAM-1) immunostaining and myocardial contractility (left ventricle dP/dtmax)
      were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced
      marked myocardial necrosis, increased serum CPK activity and myeloperoxidase
      activity (a marker of leukocyte accumulation) both in the area-at-risk and in the
      necrotic area, reduced myocardial contractility and induced a marked increase in
      the serum levels of the TNF-alpha. Furthermore increased cardiac mRNA for TNF
      alpha was measurable within 10 to 20 min of left main coronary artery occlusion
      in the area-at-risk and increased levels were generally sustained for 0.5 h.
      Finally, myocardial ischaemia-reperfusion injury increased ICAM-1 staining in the
      myocardium. Administration of cyclosporin A (0.25, 0.5 and 1 mg/kg as an i.v.
      infusion 5 min after coronary artery occlusion) lowered myocardial necrosis and
      myeloperoxidase activity in the area-at-risk and in the necrotic area, decreased
      serum CPK activity, increased myocardial contractility, reduced serum levels of
      TNF-alpha and the cardiac cytokine mRNA levels, and blunted ICAM-1 immunostaining
      in the injured myocardium. The data suggest that cyclosporin A suppresses
      leukocyte accumulation and protects against myocardial ischaemia-reperfusion
      injury.

PMID- 9932721
TI  - Effects of Ca2+ channel blockers on apomorphine, bromocriptine and morphine
      induced locomotor activity in mice.
AB  - The effects of L-type voltage-dependent Ca2+ channel blockers on apomorphine,
      bromocriptine and morphine-induced changes in locomotor activity were examined in
      mice. Apomorphine (4 mg/kg) and morphine (20 mg/kg) produced locomotor
      stimulation. Bromocriptine (8 mg/kg) produced a biphasic effect on motor
      behaviour, an early depressant phase, followed by locomotor stimulation.
      Amlodipine (2.5 mg/kg), nicardipine (10 mg/kg), diltiazem (10 mg/kg) and
      verapamil (10 mg/kg), which by itself did not affect locomotor activity,
      inhibited the stimulant phase of bromocriptine without altering the depressant
      phase, while they did not affect apomorphine- and morphine-induced locomotor
      stimulation. Apomorphine, bromocriptine and morphine-induced locomotor
      stimulation was decreased by SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3
      methyl-5-phenyl-1H-3-benzazepine-7- ol) (0.05 mg/kg) or haloperidol (0.1 mg/kg).
      These results indicate that L-type voltage-dependent Ca2+ channels are involved
      in the motor stimulant effect of bromocriptine, but not in apomorphine- and
      morphine-induced locomotor stimulation. The effects of Ca2+ channel blockers on
      the dopaminergic system appears not to be directly related to dopamine receptor
      blockade.

PMID- 9932722
TI  - Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas
      deferens.
AB  - Capsaicin-sensitive neurones release a number of neuropeptides, such as substance
      P, neurokinin A, somatostatin and calcitonin gene-related peptide (CGRP), which
      exert a number of effects on smooth muscle tissues. Endothelin-1 was thought to
      potentiate the capsaicin-evoked release of neuropeptides from sensory neurones of
      the rat. We have investigated the neuromodulatory effects of endothelin-1 on
      capsaicin-induced release of neurotransmitters from rat vas deferens. Capsaicin
      and human alpha calcitonin gene-related peptide (human alphaCGRP) reduced the rat
      vas deferens twitch responses induced by electrical field stimulation. Human beta
      calcitonin gene-related peptide-(8-37) [human betaCGRP-(8-37)] (1 microM), a
      selective alphaCGRP receptor antagonist, antagonized the inhibitory effects of
      both drugs. Endothelin-1 concentration dependently evoked an increase in basal
      tone of the musculature and potentiated the amplitude of the electrically
      stimulated responses, blocking inhibitory effects of capsaicin but not of human
      alphaCGRP. Moreover, endothelin-1 did not markedly change the inhibitory effects
      of papaverine (0.1-100 microM) or isoprenaline (1 nM-100 microM) on responses to
      electrical field stimulation. FR 139317 [(N,N-hexamethylene) carbamoyl-Leu-D
      Trp(N-Me)-D-2-Pya], a selective endothelin ET(A) receptor antagonist,
      administered 30 min before endothelin-1 restored the capsaicin effects whereas BQ
      788 [Dmpc-gamma-MeLeu-D-Trp-(1-methoxycarbonyl)-D-Nle], a selective endothelin
      ET(B) receptor antagonist, was completely ineffective. The endothelin-1-induced
      block of the capsaicin effect was resistant to tetrodotoxin (1 microM) and 30-min
      pre-treatment with MEN 10.627 (cyclo[(Met-Asp-Trp-Phe-Dap-Leu) cyclo (2beta
      5beta)]), a selective tachykinin NK2 receptor antagonist, did not abolish the
      endothelin-1 effect on the inhibitory response to capsaicin. These results
      suggest that endothelin-1 selectively inhibits the capsaicin-induced release of
      neurotransmitters from rat vas deferens and these effects are mediated via
      endothelin ET(A) receptors but not by tachykinin release.

PMID- 9932723
TI  - Quinine-induced inhibition of gastrointestinal transit in mice: possible
      involvement of endogenous opioids.
AB  - The effect of quinine, a cinchona alkaloid, was studied on gastrointestinal
      transit in mice. Intraperitoneal (i.p.) administration of quinine inhibited the
      intestinal propulsion of a charcoal suspension at a dose of 100 mg/kg, comparing
      favorably with 5 mg/kg morphine. In an attempt to probe into the mechanism
      underlying this inhibition, a possible modulation by minoxidil (1 mg/kg, p.o.)
      and glibenclamide (1 mg/kg, p.o.), the drugs that, respectively, open and close
      ATP-sensitive K+ channels was tested on gastrointestinal transit in animals
      treated or not with quinine or morphine. While minoxidil produced no significant
      change of normal transit, glibenclamide significantly increased it. However, both
      drugs blocked the quinine-induced reduction in gastrointestinal transit. In
      contrast, the inhibitory effect of morphine on gastrointestinal transit was not
      modified by either drug. The effects of quinine as well as of morphine on
      gastrointestinal transit were significantly antagonized by naloxone (2 mg/kg,
      s.c.), a mu-opioid receptor antagonist but not by yohimbine (1 mg/kg, i.p.), an
      alpha2-adrenoceptor antagonist. Furthermore, quinine at a lower dose (25 mg/kg)
      that showed no per se effect on gastrointestinal transit, significantly
      potentiated the response to 2.5 mg/kg morphine. Although the role of ATP
      sensitive K+ channels in the action of quinine and morphine was not clarified by
      the present results, a possible involvement of endogenous opioid(s) in the
      quinine-induced inhibition of gastrointestinal transit can be suggested.

PMID- 9932724
TI  - Biological activity of carboxy-terminal gastrin analogs.
AB  - Amidated forms of gastrin are derived by post-translational processing of a large
      precursor peptide and stimulate gastric acid secretion via the gastrin/CCK(B)
      receptor. Non-amidated biosynthetic intermediates may exert biological effects
      through other mechanisms, but their effect on gastric acid secretion is unclear.
      Amidated gastrins stimulate acid secretion mainly by releasing histamine from
      mucosal enterochromaffin-like cells. This study examines the effects on histamine
      release from the vascularly perfused rat stomach of amidated gastrin-17, COOH
      terminal glycine-extended gastrin-17, gastrin-17 extended at the COOH-terminal
      including the remaining progastrin sequence, and carboxy-terminal progastrin
      fragments (SAEDEN and GRRSAEDEN). Carboxy-terminal extended gastrins induced
      histamine release which was inhibited by the gastrin/CCK(B) antagonist L-740,093,
      but had to be given in concentrations 100-fold higher than amidated gastrin-17 to
      produce comparable effects. These progastrin-derived peptides are found in high
      concentrations in some patients with the Zollinger-Ellison syndrome and may
      contribute to acid hypersecretion and other gastrin/CCK(B) receptor mediated
      responses.

PMID- 9932725
TI  - The biguanide compound metformin prevents desensitization of human pancreatic
      islets induced by high glucose.
AB  - Pancreatic islet desensitization by high glucose concentrations is a temporary
      and reversible state of beta-cell refractoriness to glucose (and possibly other
      secretagogues), due to repeated or prolonged pre-exposure to increased glucose
      concentrations. We evaluated whether the oral antidiabetic agent metformin
      affects this phenomenon in isolated, human pancreatic islets, and whether the
      possible effects of the biguanide are influenced by the presence of a
      sulphonylurea, glyburide. Islets prepared from five human pancreases were
      incubated for 24 h in M199 culture medium containing either 5.5 or 22.2 mmol/l
      glucose, with or without a therapeutic concentration (2.4 microg/ml) of
      metformin. Then, the islets were challenged with either 3.3 mmol/l glucose, 16.7
      mmol/l glucose, or 3.3 mmol/l glucose + 10 mmol/l arginine, and insulin release
      was measured. After incubation in the absence of metformin, the human islets
      exposed to 22.2 mmol/l glucose showed no significant increase in insulin release
      when challenged with 16.7 mmol/l glucose (confirming that hyperglycemia
      desensitizes pancreatic beta-cells). In the presence of metformin, the islets
      fully maintained the ability to significantly increase their insulin release in
      response to glucose, even when previously exposed to 22.2 mmol/l glucose. No
      major effect on arginine-induced insulin release was observed, whatever the
      culture conditions. The protective action of metformin was observed also when
      glyburide was present in the incubation medium, whereas the sulphonylurea alone
      did not affect insulin release from the islets previously exposed to high glucose
      concentrations. These in vitro results suggest that metformin can prevent the
      desensitization of human pancreatic islets induced by prolonged exposure to
      increased glucose concentrations.

PMID- 9932726
TI  - Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an
      isoxazolidinedione derivative.
AB  - JTT-501, 4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxaz
      olidinedione, is an isoxazolidinedione derivative which is structurally distinct
      from thiazolidinediones such as pioglitazone and troglitazone. We investigated
      the effects of JTT-501 on insulin-sensitizing activity and in rodent diabetic
      models. JTT-501 enhanced insulin-stimulated cell differentiation of 3T3-L1
      fibroblasts with an EC50 value of 110 nM. Furthermore, JTT-501 activated
      peroxisome proliferator-activated (PPA) gamma and alpha receptors with the EC5
      fold values of 0.28 and 5.4 microM, respectively. In the non-insulin-dependent
      diabetes mellitus model KK-Ay mice, JTT-501 improved hyperglycemia,
      hyperinsulinemia and hypertriglyceridemia, and enhanced insulin-stimulated
      glucose oxidation in adipose tissues. JTT-501 was also effective in the non
      insulin-dependent diabetes mellitus model Zucker diabetic fatty (ZDF) rats but
      not in the insulin-dependent diabetes mellitus model streptozotocin-induced
      diabetic mice. These observations suggest that JTT-501 enhances insulin
      sensitivity in peripheral tissues and improves hyperglycemia, hyperinsulinemia,
      and hypertriglyceridemia in non-insulin dependent diabetes mellitus models. In
      particular, the triglyceride-lowering activity of JTT-501 is a unique
      characteristic compared to the thiazolidinediones. Therefore, JTT-501 may be a
      promising antidiabetic agent for treating non-insulin-dependent diabetes mellitus
      patients with insulin resistance.

PMID- 9932727
TI  - Increases in neuronal Ca2+ flux after withdrawal from chronic barbiturate
      treatment.
AB  - Chronic barbital treatment significant increased the net K+-stimulated uptake of
      45Ca2+ in cerebrocortical synaptosomal preparations, 24 h after withdrawal from
      chronic barbital administration. Basal uptake was not significantly changed.
      Hippocampal synaptosomal preparations showed a similar pattern, but the increase
      was not significant. The synaptosomal Ca2+ uptake was not affected by incubation
      with the dihydropyridine Ca2+ channel antagonist, nitrendipine, in controls or
      after chronic barbital treatment. Acute administration of a single dose of
      barbital did not alter the basal or stimulated uptake of 45Ca2+ in cortical
      synaptosomes, when this was measured 36 h after the barbital administration.
      Hippocampal slices prepared 24 h after withdrawal from chronic barbital treatment
      showed a significant increase in K+-stimulated uptake of 45Ca2+, and the basal
      uptake was significantly decreased. Both changes were prevented by nitrendipine.
      An increase in the density of dihydropyridine-sensitive binding sites was found
      in the cerebral cortex. The results indicate that both dihydropyridine-sensitive
      and insensitive neuronal Ca2+ channels are altered by chronic barbiturate
      treatment. These changes may be involved in physical dependence on barbiturates.

PMID- 9932728
TI  - Role of Ca2+-ATPase inhibitors in activation of cytosolic phospholipase A2 in
      human polymorphonuclear neutrophils.
AB  - In the present study, we investigated the involvement of Ca2+-signaling and
      protein kinases in the effect of Ca2+-ATPase inhibitors on the activation of
      cytosolic phospholipase A2 (cPLA2) in human polymorphonuclear neutrophils. We
      found that activity and mobility on electrophoresis gels of the cPLA2 protein
      were significantly increased by f-Met-Leu-Phe (fMLP), 12-myristate 13-acetate
      (PMA) and the Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid. This
      effect was completely suppressed by staurosporine. Calphostin C partially
      inhibited the fMLP- and PMA-induced cPLA 2 activation, but had no influence on
      thapsigargin- and cyclopiazonic acid-treated cells. Thapsigargin and
      cyclopiazonic acid also showed no effect on protein kinase C activity. However,
      the thapsigargin- and cyclopiazonic acid-induced cPLA2 activation was completely
      inhibited by the tyrosine kinase inhibitor, erbstatin, and Ca2+ chelator, EGTA.
      In addition, the cPLA2 activity was reduced after pretreatment with the mitogen
      activated protein kinase kinase inhibitor PD98059. The arachidonic acid release
      was significantly reduced in cells pretreated with the cPLA2 inhibitor, AACOCF3.
      Furthermore, we found that the human neutrophil cPLA2 cDNA contain a Ca2+
      dependent-lipid binding domain which shares homology to several other enzymes
      such as protein kinase C and phospholipase C. Our results suggest that tyrosine
      kinases and the MAP kinase cascade are involved in Ca2+-ATPase inhibitor-induced
      activation and phosphorylation of cPLA2. Protein kinase C is not required in this
      event.

PMID- 9932730
TI  - Effects of nicotine on K+ channel currents in vascular smooth muscle cells from
      rat tail arteries.
AB  - Intake of nicotine has been related in many cases to acute or chronic
      hypertension. Using the patch-clamp technique the effect of nicotine on voltage
      dependent K+ channel currents in rat tail artery smooth muscle cells was studied.
      Nicotine at concentrations of 1-100 microM or 0.3-3 mM increased or decreased,
      respectively, the amplitude of the tetraethylammonium-sensitive K+ currents.
      Pretreatment of cells with 10 microM dihydro-beta-erythroidine hydrobromide, a
      nicotinic receptor antagonist, abolished the excitatory effect (n=6), but not the
      inhibitory effect (n=10), of nicotine on K+ channel currents. The activation of
      nicotinic receptors with 100 microM 1,1-dimethyl-4-phenylpiperazinium iodide
      increased K+ channel currents by 27.4+/-3.8% (n=13, P < 0.01). Our results
      indicate that the excitatory and inhibitory effects of nicotine on K+ channels
      are respectively mediated by a nicotinic receptor-dependent mechanism and by a
      direct interaction of nicotine with K+ channels.

PMID- 9932729
TI  - Triflavin potentiates the antiplatelet activity of platelet activating factor
      receptor antagonist on activated neutrophil-induced platelet aggregation.
AB  - In this study, specific platelet activating factor (PAF) receptor antagonist
      ginkgolide B (BN52021) was tested for its antiplatelet activity in zymosan
      activated polymorphonuclear neutrophil-induced platelet aggregation. Triflavin
      was also tested for its antiplatelet activity compared with PAF receptor
      antagonist. Triflavin, an Arg-Gly-Asp-containing disintegrin purified from venom
      peptide inhibited platelet aggregation by interfering with the interaction of
      fibrinogen with the glycoprotein IIb/IIIa complex. Furthermore, we also report an
      efficient high resolution method for quantitative analysis of PAF using high
      performance capillary electrophoresis (HPCE). The supernatant of
      polymorphonuclear neutrophils after their activation by opsonized zymosan induces
      the aggregation of washed rabbit platelets. In rabbit platelets, BN52021 (100
      1000 microM) only partially inhibited activated polymorphonuclear neutrophil
      induced platelet aggregation, and its maximal inhibition was estimated to be
      about 79%. Triflavin also partially inhibited platelet aggregation about 82%
      induced by activated polymorphonuclear neutrophils. Furthermore, after treatment
      with a combination of triflavin (0.26 microM) with various concentrations of
      BN52021 (4-1000 microM), the inhibitory effect of platelet aggregation was almost
      completely. This inhibition was greater than that produced by the individual
      drugs alone. These results indicate that a combination of glycoprotein IIb/IIIa
      complex and PAF receptor antagonist could completely inhibit activated
      polymorphonuclear neutrophil-induced platelet aggregation. In addition, the
      amount of PAF released from zymosan (6 mg/ml)-activated polymorphonuclear
      neutrophils was accurately calculated about 11.8+/-1.5 ng/10(6) cells, and did
      not further increase even at a high concentration of zymosan (10 mg/ml). These
      results suggest that PAF play a major role in the interaction between platelets
      and polymorphonuclear neutrophils. This interaction may be important in the
      pathogenesis of thrombosis and inflammatory diseases. Our present findings
      support the hypothesis that combination therapy with glycoprotein IIb/IIIa
      complex antagonists and PAF receptor antagonists may represent a new approach to
      the treatment of ischemic disorders.

PMID- 9932732
TI  - Phosphorylation of adenylyl cyclase VI upon chronic delta-opioid receptor
      stimulation.
AB  - An immunoprecipitation method was used to measure [32P]phosphate incorporation
      into the adenylyl cyclase VI protein in Chinese Hamster Ovary (CHO) cells stably
      expressing the human delta-opioid receptor. Chronic SNC 80 ((+)-4-[(alpha R)
      alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N ,N-diethyl
      benzamide) 1 microM, 24 h) treatment increased the incorporation of [32P] into a
      200 kDa protein band 2.5-fold after gel electrophoresis. The increase in
      phosphorylation of adenylyl cyclase VI was antagonized by naltrindole (1 microM)
      and the immunoprecipitation was prevented by the saturation of the antibody with
      the blocking peptide.

PMID- 9932731
TI  - Kappa1-opioid binding sites are the dominant opioid binding sites in surgical
      specimens of human pheochromocytomas and in a human pheochromocytoma (KAT45) cell
      line.
AB  - The adrenal medulla produces opioids which exert paracrine effects on adrenal
      cortical and chromaffin cells and on adrenal splanchnic nerves, via specific
      binding sites. The opioid binding sites in the adrenals are detectable mainly in
      the medullary part of it and differ in type between species. Thus, the bovine
      adrenal medulla contains mostly kappa-opioid binding sites and fewer delta- and
      mu-opioid binding sites while primate adrenals contain mainly delta sites and few
      kappa-opioid binding sites. Most chromaffin cell tumors, the pheochromocytomas,
      produce opioids which suppress catecholamine production by the tumor. The aim of
      the present work was to identify the types of opioid binding sites in human
      pheochromocytomas. For this purpose, we characterized the opioid binding sites on
      crude membrane fractions prepared from 14 surgically excised pheohromocytomas and
      on whole KAT45 cells, a recently characterized human pheochromocytoma cell line.
      Our data showed that human pheohromocytomas are heterogeneous, as expected, with
      regard to the production of catecholamines and the distribution and profile of
      their opioid binding sites. Indeed, only one out of the 14 pheochromocytomas
      expressed exclusively delta and mu opioid sites, while in the remaining 13 tumors
      kappa-type binding sites were dominant. The KAT45 cell line possessed a
      significant number of kappa1 binding sites, fewer kappa2-opioid binding sites and
      kappa3-opioid binding sites, and minimal binding capacity for delta- and mu
      opioid receptor agonists sites. More specifically, the kappa1 sites/cell were
      approximately 18,000, the kappa2 4500/cell and the kappa3 sites 2000/cell. Our
      findings for the surgical specimens and the cell line combined with previously
      published pharmacological data obtained from KAT45 cells suggest that kappa sites
      appear to be the most prevalent opioid binding sites in pheochromocytomas.
      Finally, in normal bovine adrenals the profile of opioid binding sites differs in
      adrenaline and noradrenaline producing chromaffin cells. To test the hypothesis
      that the type of catecholamine produced by a pheochromocytoma depends on its cell
      of origin, we compared our binding data with the catecholamine content of each
      pheochromocytoma examined. We found no correlation between the type of the
      predominant catecholamine produced and the opioid binding profile of each tumor
      suggesting that this hypothesis may not be valid.

PMID- 9932733
TI  - Coordinating Y-chromosomal STR research for the Courts.

PMID- 9932734
TI  - Proof of air embolism after exhumation.
AB  - The detection, storage, and analysis of gas taken from the heart ventricle is
      necessary to diagnose a fatal air embolism and this requires special precautions
      during autopsy. When the results of gas analysis correspond to the criteria
      defined by Pierucci and Gherson the diagnosis "air embolism" is justified. In
      cases showing putrefaction the diagnostic value of gas analysis was negated. In a
      series of 15 patients who were assumed to have been killed by air injection in a
      peripheral vein the corpses were exhumed and a full medico-legal examination was
      carried out including gas analysis. In 8 cases results could be obtained
      indicating a mixture of embolised air and gases of putrefaction. In two control
      groups comprising 10 exhumed bodies and 30 cases showing advanced putrefaction,
      gas analysis showed putrefaction gases except in 5 cases with gas volumes less
      than 5 ml in the right ventricle. Therefore gas analysis can be helpful to
      diagnose fatal air embolism even in cases showing putrefaction while the
      diagnosis of putrefaction gases only does not exclude this diagnosis.

PMID- 9932735
TI  - A specific immunoassay for the determination of morphine and its glucuronides in
      human blood.
AB  - The development of specific antisera for immunochemical determination of
      morphine, morphine-3-glucuronide and morphine-6-glucuronide is described.
      Morphine was N-demethylated to normorphine and N-alkylated to give N-aminopropyl
      normorphine as hapten for antisera against morphine. As haptens for antisera
      against morphine-3-glucuronide and morphine-6-glucuronide, N-aminopropyl-nor
      morphine was glucuronidated in position 3 or 6 respectively. Each of these three
      haptens were coupled to BSA employing the glutaraldehyde method to obtain three
      different immunogens. Immunisation of rabbits with these conjugates gave anti
      morphine, anti-morphine-3-glucuronide and anti-morphine-6-glucuronide antisera,
      which were tested in a competitive, heterogeneous radioimmunoassay. Tracers for
      this radioimmunoassay procedure were synthesised by substitution of morphine and
      morphine-6-glucuronide in position 2 with 125I and indirect iodination of the
      morphine-3-glucuronide hapten according to the method of Bolton and Hunter. The
      resulting antisera show very specific reactions with morphine, morphine-3
      glucuronide and morphine-6-glucuronide. Cross reactivities of each antiserum with
      structurally related opiates and opioides are very low. The cross reactivities of
      the anti-morphine antiserum against morphine-3-glucuronide, morphine-6
      glucuronide, codeine, codeine-6-glucuronide or dihydrocodeine were less than
      0.3%, the anti-morphine-3-glucuronide antiserum against morphine, morphine-6
      glucuronide, codeine, codeine-6-glucuronide or dihydrocodeine less than 0.1% and
      the anti-morphine-6-glucuronide antiserum against morphine, morphine-3
      glucuronide, codeine or dihydrocodeine less than 0.1%, against codeine-6
      glucuronide less than 2.3%. The determination of morphine, morphine-3-glucuronide
      and morphine-6-glucuronide in blood samples (limit of detection= 3, 1, 0.5 ng/g)
      of nine cases of fatal heroin overdose with this radioimmunoassay method and the
      comparison with a GC/MS method is described.

PMID- 9932736
TI  - Y chromosome STR haplotypes: genetic and sequencing data of the Galician
      population (NW Spain).
AB  - Recently described Y-STR polymorphisms can be analysed as informative haplotypes
      which are useful in the forensic field. In order to include these systems in our
      forensic routine, we have carried out a population study in Galicia (NW Spain)
      analysing seven Y-STR polymorphisms (DYS19, DYS389-I, DYS389-II, DYS390, DYS393
      and DYS385: two loci). The results were compared with other population studies.
      In addition various alleles for each system (except DYS385) were sequenced and
      the corresponding allelic ladders constructed.

PMID- 9932737
TI  - Body and head position, covering of the head by bedding and risk of sudden infant
      death (SID).
AB  - We examined the position of the body and head, and the covering of the head by
      bedding on discovery in cases of sudden infant death (SID) in Lower Saxony.
      Between 1.1.1986 and 31.12.1992 structured, questionnaire-based interviews were
      carried out with parents of 140 SID victims. Control data were taken from a
      population-based cross-sectional study on infant sleeping position performed by
      the German Health Office (BGA) in autumn 1991. Of the SID cases 86.4% were
      discovered in the prone position [odds ratio (OR) = 7.4, 95% confidence interval
      (CI) = 4.3, 12.7] and 41.4% were found with the head covered. These infants were
      significantly older than those where the head was uncovered (p < 0.001) and
      covering of the head showed a significant association with a risk of SID (OR =
      20.8; 95% CI = 11.5-37.6). Of the SID cases 27.9% were discovered in the face
      down position. These infants were significantly younger than the infants who were
      discovered with the head in a side or supine position (p < 0.001). This study
      confirms the increased risk of SID associated with the prone position and
      suggests that this association could be related to the development of hypoxaemia
      or hypercapnia. Together with other factors such as heat stress or an infection,
      hypoxaemia or hypercapnia could culminate in SID if the arousal from sleep and
      auto-resuscitation apparently fails.

PMID- 9932738
TI  - Heteroplasmic substitutions in the mitochondrial DNA control region in mother and
      child samples.
AB  - The sequences of the two hypervariable regions of the mitochondrial DNA control
      region (HV1 and HV2) from close maternal relatives (mother-child pairs) were
      compared to determine the frequency of mutations between two generations. A total
      of 68 blood samples were sequenced only in HVI and 86 were analysed for HV1 and
      HV2. The intergenerational comparison led to the identification of six
      heteroplasmic point mutations affecting the children only. In one case a
      heteroplasmy of the maternal sequence was resolved to homoplasmy in the
      corresponding sequence of the child.

PMID- 9932739
TI  - Basement membrane thickness of the vocal cord in cases of sudden infant death.
AB  - In 1991, 1994 and 1997 Shatz et al. reported on a specific and pathognomonic
      basement membrane (BM) thickening of the vocal cord in cases of sudden infant
      death syndrome (SIDS). In 40 cases of sudden and unexpected infant death the
      histological examination of the larynx was performed to identify possible
      differences between SID (n=26) and non-SID (n=14) cases. The dissection technique
      of Hohmann (1963) and Maxeiner (1986) was modified for the infant's larynx. Since
      the normal range of the BM thickness of the vocal cord for the age group younger
      than 1 year had not yet been exactly defined, a reference interval had to be
      established (0.5 microm-2.0 microm). In 2 SID and 1 non-SID cases a mean BM
      thickness (BMT) of more than 2.0 microm could be estimated (2.38 microm-2.95
      microm). The BMT in these cases appeared to be highly variable and not
      harmonically thickened. None of the investigated regions of the BM (cranial to
      caudal thirds, ventral to dorsal areas) seemed to be preferred thickened. There
      was no statistically significant difference between the two groups. A specific
      thickening of the BM of the vocal cord in SID cases could not be confirmed.
      Therefore, BMT cannot be used as a diagnostic postmortem marker for SID.

PMID- 9932740
TI  - Higher detection rate of hepatitis G and C virus RNA in liver tissue than in
      serum of deceased injection drug users.
AB  - To examine the prevalence of hepatitis G virus (HGV) and hepatitis C virus (HCV)
      infections in deceased injection drug users and for comparison of the detection
      rates of HGV and HCV RNA in liver tissue with detection rates in postmortem serum
      samples, RT-PCR was performed in 50 drug abuse-related fatalities. HGV RNA was
      detectable in liver tissue samples from 17/50 suddenly deceased drug abusers
      (34%). In 16 of these 17 positive cases, serum samples were also available but
      HGV RNA was detected in only 10. From 29/50 anti-HCV positive individuals, HCV
      RNA was detected in 23/50 liver tissue samples (46%), but HCV RNA was detectable
      in only 6/22 of the corresponding serum samples. In 12 anti-HCV positive cases
      (10 being also positive for HCV RNA in the liver), the examinations revealed a
      coinfection with HGV by detection of HGV RNA in the liver tissue samples. A
      significant association between the detection of HCV RNA in the liver and the
      occurrence of antibodies against the HCV NS4 protein, but not against HCV core
      antigen or NS3 protein was observed. The probability of anti-HCV and HCV RNA
      positivity increased with the age of the individuals. No HGV or HCV infection was
      detected in a control group of 50 persons who died suddenly by violent impact.
      The prevalence of active HCV and HGV infections in injection drug users detected
      by RT-PCR in liver tissue is in good accordance with data obtained from sera from
      living injection drug users. In contrast, the detection rate in postmortem serum
      samples was clearly lower. Possible reasons for this observation are discussed
      and the use of liver tissue for postmortem detection of hepatitis virus RNA is
      recommended.

PMID- 9932741
TI  - Enhanced expression of selectins in human skin wounds.
AB  - The aim of the study was to characterize the vitality and age of skin wounds by
      the detection of selectins. A prospective study was conducted for this purpose in
      which 197 vital human skin wounds (time since injury ranging from 3 min to 790
      days) were investigated immunohistologically. Of the samples tested, 97 were
      taken from autopsy material and 100 from patient material from the department of
      surgery at the university hospital. The selectins were detected in paraffin
      sections after autoclaving and using the ABC technique. The intensity was rated
      by a semi-quantitative evaluation using a four-stage ordinal scale. Strong
      positive immunohistochemical reactions were observed for the P-selectin 3 min at
      the earliest and 7 h at the latest after the time of injury. For the E-selectin a
      positive staining was evident I h at the earliest and 17 days at the latest from
      the time the skin was injured. The staining intensity decreased significantly
      after an interval of 12 h from the time of injury (P < 0.05). The L-selectin was
      regularly detected on leukocytes in the samples of injured skin. The
      immunohistochemical results for the P- and E-selectins were significantly
      different between injured and uninjured skin (P < 0.01). The expression of the
      selectins is indicative of the vitality of the wound. P-selectin was detected in
      a few cases (n=4) at low intensity while E-selectin could not be found in the
      control samples (n=31) of postmortem skin wounds. The use of P- and E-selectins
      for forensic purposes can help to achieve better estimates of the age of wounds
      with short survival times.

PMID- 9932742
TI  - Reliable genotyping of short tandem repeat loci without an allelic ladder using
      time-of-flight mass spectrometry.
AB  - DNA separations which traditionally have been performed by slab gel or capillary
      electrophoresis, may now be conducted via time-of-flight mass spectrometry (TOF
      MS). The advantages of using a mass spectrometry approach for short tandem repeat
      (STR) characterization include a dramatic increase in both the speed of analysis
      and the accuracy of mass measurements. We report here typing of the STR loci
      TH01, TPOX, and CSF1PO as well as the sex-typing marker amelogenin using TOF-MS.
      Allelic ladders, which are typically used with electrophoretic separation systems
      to correct for mobility differences of DNA fragments under various conditions,
      are not needed for accurate genotyping with TOF-MS. A mass precision of 0.1% RSD,
      which corresponds to approximately 0.1 nucleotide, was routinely observed. Mass
      accuracies were better than a fraction of a single nucleotide when a daily mass
      calibration was used. STR microvariants, such as the TH01 allele 9.3, could be
      detected and resolved from alleles which differ by as little as a single base. In
      addition, the smaller PCR product sizes (55-125 bp) examined in this study have
      the potential advantage of being more successful when amplifying forensic samples
      with degraded DNA.

PMID- 9932743
TI  - Genetic variation and sequence studies of a highly variable short tandem repeat
      at the D17S976 locus.
AB  - The STR locus D17S976 was investigated by PCR amplification and native
      polyacrylamide gel electrophoresis in 158 unrelated Austrian Caucasians. No
      deviations from Hardy-Weinberg expectations were observed. The mean exclusion
      chance was 0.792, the discriminating power was 0.980 and the observed
      heterozygosity rate was 0.873. Moreover two alternative denaturing
      electrophoretic protocols are proposed. An allelic ladder consisting of 14
      sequenced alleles (236-288 bp) was constructed. Sequence analysis revealed that
      the locus contained three different repeat motifs: ATCA, ATCT and ACCT, all of
      which vary in number between alleles. The aggregate number of the three
      tetrameric repeat types was used for allele designation. As a repeat with a
      single base deletion (ATC) was found in both the smallest and the largest
      alleles, a ".3" was added to the allele designation in those cases. Therefore the
      smallest allele is designated 19.3, and the largest allele is designated 32.3. To
      evaluate the exact extent of sequence variation more extensive sequence studies
      are necessary.

PMID- 9932744
TI  - Suicidal hanging resulting in complete decapitation: a case report.
AB  - This paper reports the case of a 22-year-old man, weighing 87.5 kg, who committed
      suicide by jumping from a bridge over a canal with a nylon rope tied around his
      neck. The drop height was between 3.70 and 5.30 m before the rope tightened and
      the subject was completely beheaded. The head sank straight under the bridge,
      while the torso floated 205 m downstream. Pertinent autopsy findings were a sharp
      decapitation wound with circumferential skin abrasion and cervical spin
      transection between C1 and C2. Decapitation is a complication of extreme rarity
      in the event of a suicidal hanging and is always related to a drop of several
      metres with a poorly extensible line used as the hanging ligature.

PMID- 9932745
TI  - Ballistic aspects of tandem-loaded cartridges of identical caliber.
AB  - Tandem loading of a cartridge of the same caliber is possible only if the
      diameter of the barrel is sufficiently wide. This requirement is met by the .22
      long shot Anschutz miniature clay pigeon gun. Ballistic experiments with tandem
      loaded cartridges of the same caliber as those loaded in the normal way showed
      the bullet of the regularly loaded cartridge to impact the muzzle-loaded
      cartridge. On firing a shot, the bullet of the posterior cartridge penetrates the
      anterior one, expanding the case of the first cartridge to the diameter of the
      barrel and disintegrating the bullet. Regardless of whether the muzzle-loaded
      cartridge is ignited or not, the discharge speed of the projectiles (v0) is
      considerably below that of single shots. Calculations yielded a theoretical
      reduction by about 60%. In accordance with the formula E=1/2*m*v2, in terms of
      the energy released, the elevated mass of the projectile is of secondary
      importance compared with the reduction of v0. Although the "projectile" mass is
      more than twice the normal rate, the energy density is significantly reduced and
      the biological effect is attenuated. This also became apparent in the failed
      suicide attempt of a 43-year-old male who used a miniature clay pigeon gun to
      shoot himself in the forehead at a range of a few centimeters. He had inserted a
      second cartridge, base to head with the first cartridge, in the factory-bored
      barrel of the gun. The leading cartridge was destroyed by the regularly loaded
      one. The pierced and expanded case of the leading cartridge was found nearby the
      injured man and was at first taken to be the jacket of a larger-caliber bullet.

PMID- 9932746
TI  - Fatal injections of heroin. Interpretation of toxicological findings in multiple
      specimens.
AB  - We report two fatalities due to injection of heroin. The first case was witnessed
      but during the early phase of the police investigation the question was raised
      whether the injection was self-administered. Multiple samples were collected from
      different sites and analysed in order to establish drug distribution and to
      determine the site of injection. Fresh injection marks were found in both
      antecubital fossae but histological examination failed to settle which one was
      the last. However, toxicological analysis of the tissues at the injection sites
      indicated that the injection in the right arm was the last one. This was
      consistent with the suspicion that the victim was given the injection by another
      person although probably in agreement with the deceased. In the second case, a
      similar toxicological procedure was used. This fatality was not witnessed,
      however ample evidence indicated that it was an isolated event in a former
      intravenous heroin addict and there was only one fresh injection mark. Even in
      this case, the concentration of morphine was much higher in the tissue sample
      from the injection mark than in any of the blood samples.

PMID- 9932747
TI  - Validation studies and characterization of variant alleles at the short tandem
      repeat locus D12S391.
AB  - Validation studies were carried out on the short tandem repeat (STR) locus
      D12S391 including the determination of the allele frequencies, forensic
      application and sequence analysis of variant alleles. A total of 16 alleles were
      found in a population survey of 158 unrelated individuals from the Rhine area,
      none of which exceeded the 0.20 frequency level. In 316 alleles analysed so far
      18 alleles were found with an incomplete repeat unit in the 5'-end of the repeat
      region. The statistical values were similar to those of other European
      populations and no deviation from Hardy-Weinberg equilibrium (HWE) was observed.

PMID- 9932748
TI  - A Spanish population study of the STR loci HumLPL, D5S818, D7S820 and D13S317.
AB  - Allele and genotype frequencies for four tetrameric short tandem repeat loci were
      determined in a Spanish population sample (N=193-225) using PCR. All loci met
      Hardy-Weinberg expectations and the results demonstrated the assumption of
      independence of the loci analysed. The allele frequency data can be used in
      identity testing to estimate the frequency of a multiple PCR-based DNA profile in
      the Spanish population.

PMID- 9932749
TI  - Population genetic data on four STR loci in a Hungarian Romany population.
AB  - A population study of Hungarian Romanies was carried out on the STR loci HumLPL,
      HumF13B, HumFES and HumF1301. There was little evidence for association of
      alleles within/between the four STR systems. Allele frequency distributions were
      significantly different between the Romany and the previously reported Central
      Hungarian population databases. Population differentiation was estimated by
      computing F- and phi-statistics as well as frequency estimate differences of
      individual phenotypes for these two population samples. The results suggest that
      the population structure may have an effect on the interpretation of forensic DNA
      evidence in Hungary. Phylogenetic tree reconstruction with six populations from
      three major ethnic groups revealed a relatively distant genetic relationship of
      the Baranya Romanies with other Caucasian populations.

PMID- 9932750
TI  - Catalonian population study of the tetranucleotide repeat loci D3S1358, D8S1179,
      D18S51 and D19S253.
AB  - Allele frequencies for four short tandem repeat loci were determined in a
      population sample from Catalonia (NE Spain). After denaturing PAGE
      electrophoresis, 8 alleles were identified for D3S1358 (n=201), 10 alleles for
      D8S1179 (n=198), 13 alleles for D18S51 (n=197) and 11 alleles for D19S253
      (n=201). No deviation from Hardy-Weinberg equilibrium was found. Complete and
      relative uniformity in Caucasoid populations has been observed for D18S51 and
      D8S1179 respectively. Pronounced differences were found between different ethnic
      groups for both systems. Catalonia and Portugal do not differ for D3S1358 locus.
      Multiplex PCR amplifications of three loci (D3S1358, D18S51 and D19S253) without
      overlapping fragment size ranges could be interesting for monochrome automated
      laser fluorescence devices.

PMID- 9932751
TI  - Y-chromosome STR haplotypes in an Italian population sample.
AB  - Seven Y-chromosome STRs were investigated in a male population sample from the
      Modena area by means of one quadruplex reaction (systems DYS19, DYS390, DYS391,
      DYS393), one duplex reaction (systems DYS389-II, DYS392) and two single PCR
      reactions (DXYS156 and DYS389-I/II). In 100 males, 71 different haplotypes could
      be observed, 57 of which were seen only once. The haplotype
      diversity/discrimination index is 0.97. The resulting database could be used for
      routine forensic application like paternity testing and stain investigation.

PMID- 9932752
TI  - Local staging of esophageal cancer using endoscopic magnetic resonance imaging:
      prospective comparison with endoscopic ultrasound.
AB  - BACKGROUND AND STUDY AIMS: The magnetic resonance endoscope consists of a non
      ferrous endoscope with a radiofrequency receiver coil incorporated into its tip.
      The aim of this study was to assess the accuracy of endoscopic magnetic resonance
      imaging for the local staging of esophageal cancer. PATIENTS AND METHODS:
      Prospectively, 15 patients with biopsy-proven cancer of the esophagus (n = 9) or
      gastroesophageal junction (n = 6) underwent endosonography followed by imaging by
      the magnetic resonance endoscope. The results of endoscopic magnetic resonance
      imaging were assessed blindly, then compared with those of endosonography, which
      served as the gold standard. RESULTS: Endoscopic magnetic resonance imaging of
      transmural tumor invasion agreed with ultrasonography in 11/15 cases and of nodal
      state in 12/15 cases. Endoscopic magnetic resonance images were inadequate in
      four cases as a result of motion artifacts. CONCLUSIONS: Endoscopic magnetic
      resonance imaging of esophageal cancer diagnoses local staging that is comparable
      to endosonography. In future, the combination of endoscopic and conventional
      magnetic resonance scanning may provide comprehensive staging of esophageal
      cancer.

PMID- 9932753
TI  - Preliminary results of fine needle aspiration biopsy histology in upper
      gastrointestinal submucosal tumors.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has recently been
      reported to be useful in the diagnosis of submucosal tumors, but there are some
      cases in which the EUS diagnosis is questionable. We evaluated the diagnostic
      usefulness of endoscopic ultrasonography-guided fine needle aspiration biopsy
      (EUS-FNAB) in such cases. PATIENTS AND METHODS: From October 1993 to May 1997,
      EUS-FNAB was performed in 22 patients with upper gastrointestinal submucosal
      tumors who had also undergone EUS. We analyzed the capability of EUS-FNAB
      diagnosis compared to that of EUS imaging alone (presumptive diagnosis). RESULTS:
      Adequate specimens for histological diagnosis by EUS-FNAB were obtained in 18 of
      the 22 patients (82%). In 15 cases the final diagnosis was based on surgery. EUS
      FNAB was correct in 14 of 15 lesions. In contrast, EUS alone suggested a correct
      diagnosis in only nine lesions. CONCLUSIONS: EUS-FNAB may be able to establish a
      histologic diagnosis, and whenever histology is deemed necessary EUS-FNAB would
      be an option. EUS-FNAB may increase the diagnostic capability of EUS in
      differentiating between submucosal tumors.

PMID- 9932754
TI  - Safety and feasibility of a new minimally invasive diagnostic laparoscopy
      technique.
AB  - BACKGROUND AND STUDY AIMS: Laparoscopy combined with guided liver biopsy offers
      many advantages in the diagnosis and staging of chronic liver diseases and is
      superior to other diagnostic procedures. We developed a new minilaparoscopic
      technique and evaluated the utility of this minimally invasive laparoscopic
      system in the first 320 patients who underwent diagnostic assessment for liver
      disease or peritoneal carcinosis. PATIENTS AND METHODS: Between July 1996 and
      February 1998, minilaparoscopy, with analgesia and sedation was carried out in
      320 patients. It was done using a 1.9-mm optical instrument, which was inserted
      through the same 2.75-mm trocar as the Veress needle used for inflating the
      pneumoperitoneum. Thus only a single puncture of the peritoneum was required.
      Liver biopsies, when indicated, were obtained under laparoscopic control with the
      Silverman needle through a short 2-mm additional trocar when the Menghini
      technique was used. RESULTS: Complication rates, patient discomfort and duration
      of procedure were extremely low with minilaparoscopy. We observed no serious
      complications, two complications that could be treated conservatively and
      technical difficulties in eight of 320 patients, which prevented liver biopsy in
      2.8%. These minor difficulties all happened during the first 40 procedures,
      whereas after the initial 40 examinations of each investigator no further
      difficulties arose. CONCLUSIONS: This new minilaparoscopic technique allows a
      macroscopic and histological diagnosis of liver disease with minimal
      invasiveness, easy handling, excellent patient tolerance, and also a high degree
      of safety in patients with coagulation defects. Exploratory laparoscopy is an
      accurate and safe method for intra-abdominal diagnosis of liver diseases and
      peritoneal carcinosis.

PMID- 9932755
TI  - Biliary papillomatosis: clinical, cholangiographic and cholangioscopic findings.
AB  - BACKGROUND AND STUDY AIMS: Biliary papillomatosis (BP) is a very rare disease and
      its clinical features and outcome are not well known. The aims of this study were
      to describe the characteristic cholangiographic findings and to define the role
      of cholangioscopic examination in the diagnosis and treatment of this disorder.
      PATIENTS AND METHODS: Nine patients (six men and three women, mean age 57 years)
      were diagnosed as BP among 5361 cases of endoscopic retrograde cholangiography
      (ERC) from 1990 to 1997 in our institution. The cholangiographic and
      cholangioscopic findings as well as clinical features were retrospectively
      analyzed. RESULTS: ERC findings showed multiple small, round-to-ovoid filling
      defects in the bile duct and ductal wall irregularity in all the patients. Seven
      out of nine patients underwent percutaneous transhepatic cholangioscopic (PTC)
      examination. Additional small papillary lesions in the intrahepatic bile duct
      were detected by cholangioscopic examination in four patients whose ERC findings
      only revealed the extrahepatic lesions. Two of these four patients underwent
      curative resection. In these two patients, the initial surgical plan was changed
      from Whipple's operation to hepatico-pancratico-duodenectomy after preoperative
      cholangioscopic examination due to the detection of new lesions in the
      intrahepatic bile duct. CONCLUSIONS: ERC findings of BP were highly
      characteristic. When BP is suspected by conventional imaging including ERC,
      preoperative percutaneous transhepatic cholangioscopic examination is, however,
      strongly recommended. This procedure may be beneficial to precisely determine the
      ductal extension of the disease, hence to decide whether or not hepatic resection
      is needed as well as to confirm the histology.

PMID- 9932756
TI  - Patient-controlled sedation and analgesia, using propofol and alfentanil, during
      colonoscopy: a prospective randomized controlled trial.
AB  - BACKGROUND AND STUDY AIMS: Patient-controlled sedation (PCS) enables titration of
      dosage to an individual's requirements and is potentially useful in colonoscopy.
      The aim was to compare the value of patient-controlled sedation, using propofol
      and alfentanil, with that of intravenous diazemuls and pethidine during
      colonoscopy. PATIENTS AND METHODS: Following randomization, 66 patients
      undergoing colonoscopy received either an intravenous bolus of pethidine (50 mg)
      and diazemuls (10-20 mg) prior to colonoscopy or were connected to an infusion
      pump containing propofol (10 mg/ml) and alfentanil (25 microg/ml). Patients self
      administered 0.5 ml boluses as often as they required. Pain and sedation score
      were recorded by a nurse specialist and on a patient questionnaire. An
      anaesthetist was present throughout the procedure. RESULTS: PCS provided lighter
      sedation (median sedation score, 3 versus 4; P=0.0001), less analgesia (median
      pain score, 1 versus 0; P=0.004), a smaller maximum fall in systolic blood
      pressure (23 mmHg versus 33 mmHg; P=0.02) and a faster recovery time (median 10
      min versus 40 min; P=0.0001), irrespective of the dose administered, compared
      with a diazemuls-pethidine combination. The duration of the procedure was
      unaffected. All patients were satisfied with their level of sedation.
      CONCLUSIONS: Patient-controlled sedation is an effective alternative to
      premedication with narcotic/benzodiazepine combinations during colonoscopy.

PMID- 9932757
TI  - Endoscopic ligation for non-esophageal variceal upper gastrointestinal
      hemorrhage.
AB  - BACKGROUND: Endoscopic ligation can be used for bleeding lesions in non-fibrotic
      tissue; however, only small numbers of patients with non-esophageal variceal
      upper gastrointestinal hemorrhage have been treated in this way. To evaluate the
      utility of the technique, we performed the procedure to treat hemorrhage not from
      esophageal varices during emergency endoscopy. PATIENTS AND METHODS: Bleeding was
      identified from gastric Dieulafoy's ulcers (n=4), duodenal ulcers (n=3), gastric
      angiodysplasia (n=2) and Mallory-Weiss tears (n=3). The bleeding points were
      aspirated and controlled by endoscopic ligation and complete hemostasis was
      achieved in all cases. RESULTS: Although these lesions were located in difficult
      areas where endoscopic injection therapy and clipping sometimes fail, endoscopic
      ligation was performed easily and effectively without complications. Six of the
      patients had severe underlying disease, including acute and chronic myelogenous
      leukemia, liver cirrhosis and chronic renal failure; none suffered deterioration
      in their general condition after endoscopic ligation. CONCLUSIONS: Our findings
      suggest that endoscopic ligation is an easy and effective method of treatment for
      patients with gastrointestinal hemorrhage not from esophageal varices, and is
      safe even in patients with poor general health.

PMID- 9932758
TI  - Is urinary bladder pressure a sensitive indicator of intra-abdominal pressure?
AB  - BACKGROUND AND STUDY AIMS: The accuracy of transurethral bladder catheter
      pressure in reflecting intra-abdominal pressure is well defined in experimental
      studies and case reports but not in controlled clinical trials. PATIENTS AND
      METHODS: We compared bladder pressure with insufflator pressure during
      laparoscopic cholecystectomy in 40 patients. Measurements were made at four
      pressure levels of the insufflator: 0, 5, 10 and 15 mmHg. RESULTS: When the
      insufflator displayed 0, 5, 10, and 15 mmHg (0, 6.8, 13.6 and 20.4 cmH2O), and
      the mean bladder pressures measured 2.5 +/- 1.4, 7.3 +/- 1.5, 12.9 +/- 1.6 and
      19.7 +/- 1.5 cmH2O, respectively. The two measurements correlated well with each
      other (r = 0.973, P < 0.0001). CONCLUSION: We concluded that bladder pressure
      measured by transurethral catheter was equal to insufflator pressure during
      laparoscopy, and that this was a valid indicator of intra-abdominal pressure.

PMID- 9932759
TI  - Percutaneous endoscopic gastrostomy: an update.

PMID- 9932760
TI  - Conservative management of colonoscopic perforation can be misleading.
AB  - The management of colonoscopic perforations is still evolving. Many now agree to
      the selective management strategy: Perforations during diagnostic colonoscopy
      being treated surgically and therapeutic ones treated conservatively. However,
      patients with diagnostic perforation, if they have clean bowel and no signs of
      peritonitis, are still treated conservatively. We report here the case of a woman
      who had a perforation during diagnostic colonoscopy who was treated medically
      with good progress and no signs of peritonitis during her hospital stay for five
      days, but collapsed and died at home two days later.

PMID- 9932761
TI  - Pneumatosis cystoides intestinalis: confirmation of diagnosis by endoscopic
      puncture a review of pathogenesis, associated disease and therapy and a new
      theory of cyst formation.
AB  - Pneumatosis cystoides intestinalis (PCI) is the term for the formation of
      intramural gas filled cysts of unclear pathogenesis in the wall of the
      gastrointestinal tract. We report two patients with PCI where the diagnosis was
      confirmed by endoscopic puncture of a lesion, resulting in a complete deflation
      of the cyst, and two patients who underwent surgery. Endoscopy offers a safe and
      quick way to confirm the diagnosis of PCI. The immunohistochemical study revealed
      histiocytic cells and foreign body giant cells in the cystic wall, corresponding
      to a secondary histiocytic organization of gas-filled pseudocysts rather than to
      the widespread theory of gas-filled lymph vessels.

PMID- 9932763
TI  - DDW report New Orleans May 1998: an overview on the endoscopic abstracts.
      Digestive Diseases Week.

PMID- 9932762
TI  - Metastatic gastric cancer arising from breast carcinoma: endoscopic
      ultrasonographic aspects.
AB  - Linitis plastica of the stomach was diagnosed in four patients. Endoscopic
      ultrasonography (EUS) was performed in four cases; they were monitored by EUS and
      had their treatment adapted accordingly. According to the present study, the
      typical criteria of gastric linitis at EUS are: (a) rigidity of the gastric wall;
      (b) a wall thickness exceeding 6 mm; (c) a second enlarged layer marginally more
      echogenic than the fourth hypoechogenic layer (muscularis propria); (d) a third
      hyperechogenic enlarged layer; and (e) a poor demarcation between layers. Gastric
      linitis appears more likely to be specific metastasis from lobular breast
      carcinoma. In most of the follow-up cases, EUS showed correlation with a
      subsequent decrease of the CA15.3 level. At present, EUS seems to be the most
      effective and least invasive examination for clinical diagnosis and treatment
      surveillance of secondary gastric linitis arising from infiltrating lobular
      carcinoma (ILC) of the breast.

PMID- 9932764
TI  - Is it always true that ERCP cannot be carried out in patients with Roux-en-Y
      gastrojejunostomy?

PMID- 9932765
TI  - Recurrent common bile duct stones after endoscopic retrograde cholangioscopic
      stone removal: is there a role for associated periampullary diverticulum?

PMID- 9932768
TI  - Cytomegalovirus gastritis simulating cancer of the linitis plastica type on
      endoscopic ultrasonography.

PMID- 9932766
TI  - Guidelines of the French Society of Digestive Endoscopy (SFED): antibiotic
      prophylaxis in digestive endoscopy.

PMID- 9932767
TI  - Early massive bleeding after endoscopic ligation for junctional varices.

PMID- 9932769
TI  - Cylinder implantation--a new method for endoscopic treatment of anastomotic
      dehiscence.

PMID- 9932770
TI  - A novel approach for cannulation to the ampulla within the diverticulum: double
      catheter method.

PMID- 9932771
TI  - Laparoscopic cholecystectomy: unusual septic complications because of gallstone
      spillage.

PMID- 9932773
TI  - Description and first evaluation of colonoscopy technique with a new external
      straightener of the colon.

PMID- 9932772
TI  - Ovary sealing colonoscopic perforation.

PMID- 9932774
TI  - Endoscopic ligation for bleeding rectal varices in a child with primary
      extrahepatic portal hypertension.

PMID- 9932775
TI  - Esophageal Crohn's disease with esophagopleural fistula.

PMID- 9932776
TI  - Gastric stenosis after potassium chloride ingestion.

PMID- 9932777
TI  - Endoscopic image of early mucinous carcinoma of the sigmoid colon.

PMID- 9932778
TI  - [Antibiotic prophylaxis in digestive endoscopy].

PMID- 9932779
TI  - Endoscope technology in the future.

PMID- 9932780
TI  - 25 years of endoscopic sphincterotomy in Erlangen: assessment of the experience
      in 3498 patients.
AB  - BACKGROUND AND STUDY AIMS: The aim of the study was to investigate the evolution
      of endoscopic sphincterotomy (EST) over a period of 25 years at its birthplace in
      Erlangen, Germany. PATIENTS AND METHODS: A total of 3498 consecutive ESTs between
      1973 and the end of 1997 were reviewed with respect to indications, technology,
      success, complications, therapy of complications and mortality. In order to
      demonstrate changes in the course of time, the results have been compiled
      separately for four time periods (A-D). RESULTS: During the 25 years' practice of
      EST in Erlangen the frequency of ETSs has increased constantly and significant
      changes have been observed concerning the spectrum of indications: Bile duct
      stones (total 55.1%) decreased continuously from 91.1% (period A) to 35.7%
      (period D). In contrast, the proportion of ESTs applied for malignant obstruction
      (total 22.1%) rose successively from 1.1% (period A) to more than 25% (periods B
      D). Chronic pancreatitis as an indication for EST was established in period B
      (1.0%) and accounted for 20.2% of all procedures in period D (total 8.0%).
      Several new indications (summarized as "others") increased from 1.8% in period A
      to 11.9% in period D (total 6.7%) whereas biliary pancreatitis and scarred
      papillary stenosis remained constantly below 5%. Whereas the "Erlangen
      sphincterotome" was the only sphincterotome used in period A, it was almost
      completely replaced by guide-wire sphincterotomes in period D. With the
      introduction of the needle knife the precut technique became popular and was used
      with increasing frequencies: period B 31.9%, period C 34.1%, period D 41.9%. The
      success rate in total was 95.2%. For each time period the highest success rate of
      EST was obtained for bile duct stones (96-98%), whereas EST appeared to be more
      difficult in case of malignant obstruction (93.3%) or chronic pancreatitis
      (90.2%), but for both indications growing experience resulted in an increase in
      the success rates (85.7% to 94.9% and 90.9% to 94.0%, respectively).
      Complications occurred in 7.9% of cases. The complication rate declined
      significantly from 10.5% in period A over 7.6% in period B to 6.3% in period C.
      Prospective data acquisition in period D revealed a significant increase in the
      detection of mild forms of acute pancreatitis, resulting in a slight increase of
      the complication rate (8.4%). Needle-knife papillotomy did not significantly
      increase the complication rate. Whereas in period A 41% of all complications were
      managed by surgery, this value dropped over 28% (period B) and 7.5% (period C) to
      ultimately 1.6% in period D. The method-related mortality was nearly constant
      over the whole period of time (0.6%). CONCLUSIONS: Despite a continuous shift of
      indications and a changing mixture of learning endoscopists and EST experts over
      25 years, the practice of EST at its birthplace in Erlangen has shown a
      constantly high success rate, a decreasing complication rate and an acceptable
      but mainly unchanged mortality rate. Currently, nearly all complications can be
      successfully managed nonoperatively.

PMID- 9932782
TI  - The future of endoscopic retrograde cholangiopancreatography: what is necessary
      and what should be improved?

PMID- 9932781
TI  - The development of biliary drainage and stenting.

PMID- 9932783
TI  - Cost-effectiveness of endoscopic sphincterotomy.

PMID- 9932784
TI  - Complications of endoscopic sphincterotomy.

PMID- 9932785
TI  - Long-term sequelae of endoscopic papillotomy.

PMID- 9932786
TI  - Endoscopic papillotomy: surgery should not be forgotten.

PMID- 9932787
TI  - Clinical impact of sphincter of Oddi dyskinesia.

PMID- 9932788
TI  - The role of sphincter of Oddi manometry and biliary microscopy in evaluating
      idiopathic recurrent pancreatitis.

PMID- 9932789
TI  - Which stents do we need? The case for plastic stents.

PMID- 9932790
TI  - Metal stents for benign and malignant bile duct strictures stents for benign and
      malignant bile duct strictures.
AB  - Self-expanding metal stents provide a much larger diameter--up to 30 Fr--in
      comparison with plastic stents, which have a maximum diameter of 12 Fr. Although
      they have consequently been found to be far superior to plastic prostheses, they
      are not removable, and in benign strictures metal stents should therefore be used
      only in exceptional situations. Metal stents are the preferred mode of treatment
      for malignant strictures, provided the patient has a sufficient life expectancy
      although this is hard to predict in individual cases. Metal stents also seem to
      be superior in hilar malignancy, but the data here are limited. Future
      developments may include the use of covered metal stents and self-expanding
      stents (made of plastic or other materials) that are removable or self
      dissolving.

PMID- 9932791
TI  - The role of ERCP and sphincterotomy in acute biliary pancreatitis.

PMID- 9932792
TI  - Biliary pancreatitis needs endoscopic retrograde cholangiopancreatography with
      endoscopic sphincterotomy for cure.

PMID- 9932793
TI  - Polymerase chain reaction-single strand conformation polymorphism or how to
      detect reliably and efficiently each sequence variation in many samples and many
      genes.
AB  - A simple and fast method with high reliability is necessary for the
      identification of mutations, polymorphisms and sequence variants (MPSV) within
      many genes and many samples, e.g. to clarify the genetic background of
      individuals with multifactorial diseases. We evaluated polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP) analysis to identify MPSV in
      several genes, which are thought to be involved in the pathogenesis of
      multifactorial autoimmune diseases like multiple sclerosis. The method is based
      on the property, that the electrophoretic mobility of single-stranded nucleic
      acids depends not only on its size but also on its sequence. The target sequence
      was amplified, digested into fragments ranging from 50-200 bp, heat-denatured and
      analyzed on native gels. The analysis of 55 PCR systems, including a total of 145
      fragments demonstrates, that the detection rate of MPSV depends primarily on the
      fragment lengths. Appropriate dilutions of samples enhances the proportion of
      ssDNA compared to dsDNA. Changing the gel conditions, glycerol concentrations
      and/or the addition of urea may increase fragment resolution in some cases. In
      general, the detection of MPSV is neither influenced by their location within the
      fragment nor by the type of substitution, i.e. transitions or transversions. The
      standard PCR-SSCP system described here provides high reliability and detection
      rates and allows the efficient analysis of many samples and many genes.

PMID- 9932794
TI  - Preparative separation of plasmid and bacterial artificial chromosome DNA by
      density gradient electrophoresis in the presence of linear polymers.
AB  - A density gradient apparatus was used to examine the separation of different
      physical forms and sizes of DNA. A gradient of sucrose was used to stabilize
      thermal convection during electrophoresis in the column (2.2 cm in diameter).
      Linear polymers were added to the density gradient and screened for their ability
      to separate the supercoiled, nicked circular, and linear forms of the plasmid pBR
      322. The influence of different concentrations and molecular weights of the
      polymers was examined on the separation. Polyethylene oxide with a molecular
      weight of 5,000,000 and a concentration of 0.2% w/v achieved the best separation
      results for the different physical forms of the plasmid. The order of separation
      of the different physical forms of the plasmid were linear (fastest),
      supercoiled, and nicked circular (slowest). These conditions were also used to
      separate a preparation of bacterial artificial chromosome (BAC) DNA. A rapidly
      moving form, presumably the supercoiled form, was resolved from a large amount of
      E. coli genomic DNA and from sheared forms of the BAC DNA.

PMID- 9932795
TI  - DNA preparation and efficient microsatellite analysis from insect hemolymph.
AB  - A simple and time-saving method for DNA preparation for efficient microsatellite
      analysis is described. The method is based on thermal treatment of only 1-5
      microL of insect hemolymph in a Chelex 100-suspension. Since hemolymph withdrawal
      does not harm the insects, analysis of mating systems, population structure and
      phylogenetic reconstruction can be conducted with minimal experimental influence.

PMID- 9932796
TI  - Characteristics of selective polymerase chain reaction (PCR) using two-base
      anchored primers and improvement of its specificity.
AB  - We have developed a reliable method for eliminating base-mispair amplification in
      selective polymerase chain reaction (PCR), which is utilized for amplifying
      unknown sequence fragments produced by restriction enzyme reaction. The proposed
      procedure applies amplified fragment length polymorphism (AFLP) with high
      fidelity. Selective PCR utilizes the known polymerase reaction characteristic
      that the complementary strand extension is strongly affected by matching a
      template with the 3'-terminus of the primers. However, false positive
      amplification is frequently observed because the specificity of terminal bases
      for discrimination of fragments (usually, 1-3 anchor sequences) is not enough to
      separate each fragment. A protocol for the selective PCR separation of every
      fragment was therefore investigated. A single-base mismatch was artificially
      introduced on the 4th base position from the 3' end of the primers to improve the
      hybridization specificity of anchored 2-bases at the 3' termini of primers. PCR
      reaction was carried out at 66 degrees C to prevent false positive amplification.
      The concentration of the primers having anchored-base sequences of AA, AT, TA,
      and TT must be three times larger than that of other primers because the Tm
      values for these sequences are lower than the others. As all the fragments can be
      separated into groups with high fidelity, the improved selective PCR will be
      applied to gene finding and analyzing differences on genome sequences based on
      AFLP.

PMID- 9932797
TI  - Multiplexed short tandem repeat polymorphisms of the Weber 8A set of markers
      using tailed primers and infrared fluorescence detection.
AB  - Short tandem repeat polymorphism (STRP) markers have become important reagents
      for mapping genetic diseases. These markers are available as screening sets,
      which are located in all chromosomes at discrete intervals, allowing the entire
      genome to be analyzed. Mapping studies that include many individuals in the
      analysis necessitate the production of large numbers of genotypes. In an effort
      to increase the efficiency and lower the cost of using these STRP screening sets,
      we have divided the amplification primers of the Weber 8A screening set into
      groups that can be amplified in single polymerase chain reaction (PCR)
      amplification reactions, resulting in a reduction of both time and cost.
      Fluorescently-labeled amplification products were produced using a three primer
      reaction. The forward STRP amplification primer for each marker contained a 19 bp
      sequence at the 5' end. A fluorescently-labeled primer, with a sequence identical
      to the 19 bp tail, was added to the amplification reaction as the sole source of
      fluorescent label. The STRP banding pattern is detected using an automated
      fluorescent DNA sequencer. Use of this multiplexed genomic screening set should
      greatly enhance the mapping of human disease loci.

PMID- 9932798
TI  - Minisatellite variant repeat (MVR) analysis of the HRAS1 minisatellite locus.
AB  - Two alternative electrophoretic strategies were used to study the internal
      variation of the HRAS1 minisatellite after minisatellite variant repeat mapping
      (MVR-PCR) was carried out. While the use of automated sequencers with fluorescent
      based technology is ideal for analyzing fragment size, and therefore, for
      analyzing the repeat number, the use of polyacrylamide gels and silver staining
      is more appropriate for the analysis of internal variation. Thirteen different
      fragments ranging from 27 to 80 repeats were found in a sample from 80 healthy
      Caucasian individuals. By using MVR mapping we were able to detect heterozygotes
      which appear as homozygotes when fragment length analysis was used. As a result
      of this, the 13 alleles, which we had detected, increased to 16 alleles when MVR
      sequences were analyzed. The extremely conservative arrays of repeats allow us to
      infer the theoretical origin of rare alleles from a major group of specific
      alleles. The HRAS1 minisatellite has been extensively studied due to its
      association with cancer. However, the methodology used up to now has limited the
      scope of previous research. Our approach permits the identification of alleles in
      a fast and reliable way using their MVR codes, thus allowing association studies
      with cancer.

PMID- 9932799
TI  - Interval isotachophoresis for purification and isolation of ionogenic species.
AB  - A new preparative electrophoretic method in free solution is described,
      consisting of three consecutive steps: (i) filling the separation chamber with a
      suitable electrolyte system and sample in parallel streams by laminar
      hydrodynamic flow, (ii) applying the voltage across the chamber with
      isotachophoretic separation for a definite time interval operating in the
      direction perpendicular to that of filling, (iii) reapplying a hydrodynamic flow
      (without voltage) and collecting the separated species via an array of outlets.
      This approach completely eliminates the main drawback of the continuous flow
      electrophoresis (CFE), i.e., the electrohydrodynamic distortion of zones. This
      method utilizes the instrumentation devised for CFE and enables the isolation of
      large amounts of individual sample species comparable to that of CFE, with a
      resolution comparable to that of capillary isotachophoresis. The precise timing
      of the consecutive steps in the procedure as well as the stability of the
      operational parameters are of key importance for reproducibility. By using
      cationic isotachophoresis with 3 synthetic pI markers as model sample species,
      the reproducibility, stability and the separation power of the newly presented
      method are demonstrated. The sample throughput corresponds to micromoles per
      hour.

PMID- 9932800
TI  - Stability of continuous flow electrophoresis.
AB  - The stability of continuous flow electrophoresis (CFE) was tested by performing
      uninterrupted continuous flow cationic isotachophoresis for 15 h, using a mixture
      of two synthetic isoelectric point (pI) markers as the model sample. This sample
      as well as the other operational electrolytes were continuously pumped into the
      CFE separation chamber via 10 individual inlets. The operational electrolyte
      system and the arrangement of the electrolyte streams were selected in accord
      with previously published results, providing a stable electrophoretic regime. The
      chamber had 96 individual outlets and here 96 individual fractions were collected
      in microwell plates in regular time intervals and scanned photometrically. The
      scanned photometric patterns proved that CFE is sufficiently stable for an
      overnight operation.

PMID- 9932801
TI  - Preparative application of commercial automated gel electrophoresis apparatus to
      subcellular-sized particles: sequential isolations, fractions re-run, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis, yield and purity.
AB  - The analytical and preparative potential of automated gel electrophoresis
      apparatus with intermittent fluorescence scanning of the migration path, the HPGE
      1000 apparatus (LabIntelligence, Belmont, CA) was further developed in
      application to subcellular-sized particles. Resolution between two rat liver
      microsome components in agarose (MetaPhor) gel electrophoresis was found to
      increase with decreasing agarose concentration to 0.04%. It was less, even in an
      agarose solution at that low concentration, than that in laterally aggregated 4%
      polyacrylamide gel. The three components of the microsomal preparation were
      sequentially isolated from 0.6 and 0.8% agarose gel electropherograms. One
      fraction when re-electrophoresed was found to exhibit the original mobility and
      did not give rise to the other components. Yields of each component were near
      quantitative after one or two electroelution steps. Based on protein content, no
      impurities could be detected in two of the microsome fractions; the third
      fraction contained 2% of nonmicrosome impurity. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) patterns of all three microsome
      fractions were indistinguishable from one another and from that of the
      unfractionated microsome preparation.

PMID- 9932802
TI  - Identification of animal species in ground meat mixtures by multivariate analysis
      of isoelectric focusing protein profiles.
AB  - The present work investigates the possibility of constructing a multivariate
      calibration model to predict the composition of ground meat with respect to
      animal species, based on intensity profiles from isoelectric focusing of water
      soluble proteins in mixtures of ground meat. Samples containing various amounts
      of beef, pork and turkey meat were analyzed by isoelectric focusing in
      immobilized pH-gradients. The gels were photographed and the images transferred
      to a digital format. The digital images were processed in order to reduce
      background and optimize signal strength. Resulting gel profiles were analyzed by
      multivariate regression allowing the determination of sample composition with
      prediction errors close to 10%.

PMID- 9932803
TI  - Comparative analysis of genus Vigna seeds using antiserum against a synthesized
      multiple antigenic peptide.
AB  - Antiserum for 33 kDa vicilin-like seed proteins in V. angularis was prepared
      using a synthesized multiple antigenic peptide (MAP). The anti-MAP antiserum was
      applied to the protein analysis of all of genus Vigna seeds which are stored in
      the Gene Bank at the National Institute of Agrobiological Resources, Tsukuba,
      Japan. The anti-MAP antiserum specifically reacted with 33 kDa vicilin-like
      proteins and weakly with 55 kDa vicilin-like proteins of V. angularis by
      immunoblotting and could distinguish between these two types of vicilin-like 7 S
      proteins. Anti-MAP antiserum reacted with 33 kDa band both in wild and cultivated
      types of V. angularis (4 spots) and half species of V. radiata (2 spots). The N
      terminal amino acid sequence of the major immunoreacting spot in V. radiata seeds
      was analyzed. A partially homologous amino acid sequence with MAP was found in
      immunoreacted protein and the anti-MAP antiserum was able to be applied as a
      probe to identify homologous amino acid sequence in other proteomes. V. radiata
      species could be divided by their immunoreactivities into two groups: the group
      from Southeast Asia and Australia, which reacted with the anti-MAP antiserum, and
      the group from West Asia and Madagascar, which did not. The abundant proteins in
      V. mungo seeds at 55 kDa showed strong reactivity signals with anti-MAP
      antiserum. The existence of a homologous amino acid sequence with MAP was
      suggested in the 55 kDa proteins. The seed proteins in V. aconitifolia, V.
      umbellata, V. vexillata, V. marina, V. unguiculata, and V. oblongifolia did not
      show any reactions and they do not possess the homologous amino acid sequence
      with MAP in their seed proteins.

PMID- 9932804
TI  - Finding a universal low viscosity polymer for DNA separation (II).
AB  - When investigating the use of different polymers for capillary electrophoresis we
      found that poly-N,N-dimethylacrylamide (pDMA) has a very low viscosity compared
      to other polymers of comparable molecular mass and resolving power. This makes it
      a potentially useful matrix for DNA separation in multi-capillary
      electrophoresis, where short cycle times or low pressure for matrix replacement
      are preferred. We have characterized this matrix by systematic studies on
      concentration, chain length and field strength dependence. It is shown that pDMA
      performs well for the separation of oligonucleotides and double-stranded DNA
      fragments. Together with the application of DNA sequencing, pDMA is a universal
      polymer for the separation of biological macromolecules.

PMID- 9932805
TI  - A theory for the electrophoretic separation of DNA in polymer solutions.
AB  - We present a mathematical model of DNA capillary electrophoresis in polymer
      solutions based on nonentangling collisions between DNA and polymer molecules.
      Using videomicroscopy images of DNA migrating through polymer solutions, we
      propose a modified transient entanglement coupling mechanism for DNA separations
      that includes nonentangling DNA/polymer collisions. We show that a mathematical
      model based on individual nonentangling DNA/polymer collisions is able to predict
      the mobilities of DNA in solutions of low molecular mass polymer. We compare the
      model predictions to mobility data for separations of DNA in a range of
      concentrations for solutions of both hydroxypropylcellulose (Mw 100,000) and
      hydroxyethylcellulose (Mw 139,000). The model relies on one fitted parameter, the
      time constant for the interaction between the DNA and polymer molecules, which is
      based on the physical properties of DNA and polymers.

PMID- 9932806
TI  - High-frequency alternating-crossed-field gel electrophoresis with neutral or
      slightly charged interpenetrating networks to improve DNA separation.
AB  - Toward improving DNA separations, this work reports the effects of high-frequency
      square-wave AC fields superimposed perpendicular to the direct current (DC)
      separation field on DNA migration in both polyacrylamide-based interpenetrating
      networks (IPNs) and in agarose networks. Compared to standard polyacrylamide
      gels, IPNs allow the separation of larger DNA (9000 bp vs. 5000 bp at 5 V/cm). In
      novel polyacrylamide-based IPNs, an alternating current (AC) field of 5 Hz
      increased the maximum DNA size separable. This effect was extended to larger DNA
      sizes with increasing electric-field strength up to and apparently beyond the
      power supply-limited maximum electric-field strength of 48 V/cm. The orthogonal
      AC field also increased mobility. These two results combine to yield a reduction
      in separation time of up to a factor of 20 in novel polyacrylamide-based IPNs.
      When negatively charged acrylic-acid groups were incorporated into the IPNs, the
      use of the AC field changed the DNA-network interaction, which altered the size
      dependence of DNA mobility. In agarose gels, an AC field of 50 Hz increased the
      size range separable; however, there was no increase in DNA mobility. There was
      no change in size dependence of mobility in an AC field when the number of
      charged groups in the agarose network was increased. Based on results in the
      literature, possible mechanisms were examined for the effects of the AC field on
      DNA separation.

PMID- 9932807
TI  - Capillary electrophoretic separation of 1 to 10 kbp sized dsDNA using
      poly(ethylene oxide) solutions in the presence of electroosmotic counterflow.
AB  - DNA fragments of 1 to 10 kbp in length were separated by capillary
      electrophoresis (CE), using poly(ethylene oxide) (PEO) solutions in the presence
      of electroosmotic flow. The technique requires filling the capillary with the
      polymer solution by means of electroosmotic flow (EOF). Separation times of 6-7
      min in PEO solutions ranging from 0.3 to 8 x 10(6) Mr at 375 V/cm were sufficient
      to separate the 11 components of the dsDNA ladder (0.5 to 10 kbp) by size. The
      migration behavior of the double-stranded (ds)DNA fragments, interpreted by
      "Ferguson plot analysis", in the system is indistinguishable from that previously
      reported for capillary zone electrophoresis (CZE) in a polyacrylamide solution
      without EOF. Potential advantages of conducting CZE using polymer solutions in
      the presence of EOF are: (i) Possibility of long migration times on short
      columns; (ii) possibility of introducing relatively viscous, high Mr polymer
      solutions into narrow capillaries; (iii) possibility of establishing polymer
      concentration gradients in capillaries; (iv) possibility of concentrating the
      starting zone by balancing electrophoretic migration and electroosmotic
      transport.

PMID- 9932808
TI  - Separation of oligonucleotides and DNA fragments by capillary electrophoresis in
      dynamically and permanently coated capillaries, using a copolymer of acrylamide
      and beta-D-glucopyranoside as a new low viscosity matrix with high sieving
      capacity.
AB  - New copolymers of acrylamide and beta-D-glucopyranoside were synthesized and
      characterized. The different reactivity of the two monomers towards radical
      polymerization meant we could control the growth of the polymer chains whose
      length was inversely related to the number of glucose residues incorporated in
      the copolymers. The properties of these polymers were investigated in the
      separation of oligonucleotides and double-stranded DNA by capillary
      electrophoresis (CE) in coated and uncoated capillaries. The new copolymers were
      a suitable matrix for CE due to their high-resolving capacity and low viscosity.
      We also looked into the advantages of a new method of dynamic suppression of
      electroosmotic flow based on the addition of small amounts (0.03-0.05%) of
      dimethylacrylamide to the sieving and to the running buffer. A complete test was
      run on the reproducibility and efficiency of separations carried out in a
      permanently and dynamically coated capillary, and the advantages and
      disadvantages of the two methods were compared.

PMID- 9932809
TI  - Capillary electrophoretic analysis of synthetic short-chain oligoribonucleotides.
AB  - Thirty synthetic oligoribonucleotides, 3 to 18 nucleotides (nt) long, were
      analyzed by capillary electrophoresis, under nondenaturing conditions, using a
      commercial kit. The migration time t(m) was dependent on nt length and
      composition, capillary length, operating temperature, and type of sieving
      polymer. Under fixed experimental conditions, the t(m) proved predictable by the
      equation: t(m) = [0.22(n-1) + 6.14A/n + 6.86G/n + 3.61 (C+U)/n] min, for n>3,
      where A/n, G/n, C/n, U/n is the frequency of each type of nt within the
      oligonucleotide (ONT). The equation accounts for the influence of charge-to-mass
      ratio on t(m), but not for structural effects, if present. This approximation is
      acceptable for short ONTs. The possibility of detecting n+1, n-1, n-2 impurities,
      having predicted the t(m), is of crucial importance in assessing the purity of
      synthetic ONTs dedicated to structural studies. This appears to be feasible. High
      resolution was shown among homologous series of ONTs of increasing length, and in
      some cases, even within groups of ONTs of the same length but different
      composition. The addition of 7 M urea to the buffer, as denaturing agent,
      accelerates the t(m) and significantly lowers the resolution for the shortest
      ONTs. It was also possible to monitor the state of association of mixtures of RNA
      and DNA sequence-complementary strands.

PMID- 9932810
TI  - A simple method for the determination of isoelectric points of ampholytes with
      closely spaced pKa values using pressure-mediated capillary electrophoresis.
AB  - A simple method, based on a modified version of pressure-mediated capillary
      electrophoresis (PreMCE) has been developed for the determination of the
      isoelectric points of ampholytes which have closely spaced pKa values. This new
      pI-determination PreMCE method (i) can be easily executed on most commercial
      capillary electrophoresis instruments; (ii) it can use small, impure samples,
      (iii) unlike isoelectric focusing methods in natural pH gradients, it does not
      require a linear pH gradient, and (iv) it eliminates the pI errors that are due
      to chromatographic retention on the walls of the separation chamber.

PMID- 9932811
TI  - Development and validation of transient isotachophoretic capillary zone
      electrophoresis for determination of peptides.
AB  - Although capillary zone electrophoresis (CZE) is known for its high resolution
      power and low mass detection limits, the concentration detection limits are
      rather poor when ultraviolet absorbance detection is used. To overcome this
      limitation, several on-column transient isotachophoresis (tITP) protocols have
      been developed and validated for the determination of both cationic and anionic
      model peptides, separately. Using this preconcentration method, up to 72% of the
      capillary can be filled with sample solution, without any loss in resolution.
      Thus, without any modification of the hardware set-up, the sensitivity is
      increased about two orders of magnitude. For the model cationic peptides
      (gonadorelin, angiotensin II) good linearity and reproducibility is observed in
      the 20 to 100 ng/mL concentration range. For the anionic peptides (N-t-Boc
      Pentagastrin and two related peptides), a tITP method was developed using a
      dynamically coated capillary. The coating was prepared by adding Fluorad FC-135
      to the leading electrolyte buffer. In this way a positively charged bilayer was
      formed on the inside of the capillary, producing an electroosmotic flow towards
      the outlet using reversed polarity conditions. In this way, acceptable analysis
      times were achieved. Using the developed tITP method, up to 72% of the capillary
      can be filled with sample solution as well. The anionic peptides are separated
      even better than when using CZE conditions. Linearity and reproducibility in the
      20-100 ng/mL range proved to be excellent.

PMID- 9932812
TI  - Nonaqueous capillary electrophoretic separation and thermo-optical absorbance
      detection of five tricyclic antidepressants and metabolism of amitriptyline by
      Cunninghamella elegans.
AB  - We developed a technique based on nonaqueous capillary electrophoresis and laser
      based thermo-optical absorbance detection to assay five antidepressants with
      similar structures and mass-to-charge ratios. A mixture of methanol and
      acetonitrile with ammonium acetate was essential to achieve baseline resolution
      of these compounds. We investigated the effects of ammonium acetate
      concentration, temperature, applied voltage, and capillary length on separation
      efficiency. The nonaqueous capillary electrophoresis and laser-based thermo
      optical absorbance detection technique was used to study the metabolism of
      amitriptyline by Cunninghamella elegans. Sample preparation procedures were
      simplified for fast screening of the parent drug and its metabolites.
      Reproducible electropherograms were obtained from replicate cultures of C.
      elegans growing in the presence of amitriptyline.

PMID- 9932813
TI  - On-line nonaqueous capillary electrophoresis and electrospray mass spectrometry
      of tricyclic antidepressants and metabolic profiling of amitriptyline by
      Cunninghamella elegans.
AB  - An on-line nonaqueous capillary electrophoresis-electrospray mass spectrometry
      (ESI-MS) technique was developed using a commercial ion spray interface. The
      nonaqueous capillary electrophoresis ESI-MS system was used to profile tricyclic
      antidepressants of similar structures and mass-to-charge ratios. We found that
      pure methanol can be used as a sheath liquid to obtain stable ion spray from
      nonaqueous capillary electrophoresis. The flow rate of the coaxial nebulizing gas
      affected baseline signals, separation efficiency, and migration times. Other
      nonaqueous capillary electrophoresis operating conditions and electrospray
      parameters were optimized for enhanced baseline separation and high sensitivity
      detection. The effect of sample stacking on separation and detection was
      evaluated. The calculated detection limits were approximately 3 pg injected onto
      the capillary. ESI mass spectra of tricyclic antidepressants from a single
      quadrupole MS were obtained and elucidated. The information was used to propose
      fragmentation pathways of the tricyclic antidepressants. The method was also used
      to analyze the metabolites of amitriptyline produced by the fungus Cunninghamella
      elegans. Sixteen metabolites were detected and most of them were tentatively
      identified as demethylated and/or hydroxylated, and/or N-oxidized products.

PMID- 9932815
TI  - Multiple parameter cross-species protein identification using MultiIdent--a world
      wide web accessible tool.
AB  - Recent increases in the number of genome sequencing projects means that the
      amount of protein sequence in databases is increasing at an astonishing pace. In
      proteome studies, this is facilitating the identification of proteins from
      molecularly well-defined organisms. However, in studies of proteins from the
      majority of organisms, proteins must be identified by comparing analytical data
      to sequences in databases from other species. This process is known as cross
      species protein identification. Here we present a new program, MultiIdent, which
      uses multiple protein parameters such as amino acid composition, peptide masses,
      sequence tags, estimated protein pI and mass, to achieve cross-species protein
      identification. The program is structured so that protein amino acid composition,
      which is highly conserved across species boundaries, first generates a set of
      candidate proteins. These proteins are then queried with other protein parameters
      such as sequence tags and peptide masses. A final list of database entries which
      considers all analytical parameters is presented, ranked by an integrated score.
      We illustrate the power of the approach with the identification of a set of
      standard proteins, and the identification of proteins from dog heart separated by
      two-dimensional gel electrophoresis. The MultiIdent program is available on the
      world-wide web at: http://www.expasy.ch/sprot/multiident.h tml.

PMID- 9932814
TI  - Faster capillary electrophoresis separation of wheat proteins through
      modifications to buffer composition and sample handling.
AB  - Studies were conducted to produce faster, simpler, more rugged protocols for
      separating wheat proteins by high performance capillary electrophoresis (HPCE).
      Three areas were targeted for improvement: initial capillary equilibration
      procedures, buffer composition, and post-separation rinsing procedures. For the
      initial equilibration of capillaries, a brief rinse with a
      hydroxypropylmethylcellulose (HPMC) solution was the most critical factor for
      successful separation of wheat proteins. To reduce separation time and maintain
      resolution, beta-alanine and glycine were each used in place of sodium phosphate
      as buffer ions. Two isoelectric buffers, aspartic acid and iminodiacetic acid
      (IDA) were also tested. Each of these four buffer systems generated substantially
      lower currents, and provided faster separations, than sodium phosphate-based
      buffers. Finally, post-separation rinsing procedures were re-examined with the
      goal of reducing the time necessary to rinse the capillary after each separation.
      A critical factor in achieving this goal was removal of albumins and globulins
      prior to separation. These proteins bind to the capillary wall and cause rising
      baselines and excessive peak tailing. Once these proteins were removed,
      capillaries could be rinsed with buffer for only 2 min between separations.
      Capillary equilibration procedures were shortened from 90 min to 30 min.
      Likewise, separation times were reduced by approximately 40% (25 min to 15 min)
      by using glycine in place of sodium phosphate in the separation buffer. Finally,
      post-separation times were reduced by 80% (10 min to 2 min). Overall, these
      factors resulted in a reduction in total separation time of 50% (35 to 17 min)
      and maintained high resolution separations and good run-to-run repeatability.

PMID- 9932816
TI  - Cholangiocyte-specific rat liver proteins identified by establishment of a two
      dimensional gel protein database.
AB  - The liver is composed of a variety of cells that form a functional unit involved
      in uptake, synthesis, metabolism, and secretion. Until recently, most studies
      examining liver function did not analyze the specific proteins expressed or
      functions performed by the multiple individual cell types that constitute the
      hepatic mass. In the last decade, novel isolation methods have been developed
      that allow the purification of liver cell populations highly enriched in one type
      of liver cell. Here, we present a detailed two-dimensional (2-D) protein map of
      rat bile duct epithelial cells (i.e., cholangiocytes) using a recently developed
      isolation procedure. In addition, we identify 27 major cholangiocyte proteins
      either by comparison to maps of known rat liver proteins (based on pI and Mr) or
      by tryptic digestion and microsequencing. Finally, we compare the relative
      abundance of individual proteins present in cholangiocytes to whole liver as well
      as hepatocyte-specific proteins. Our results show that cholangiocytes express a
      unique array of individual proteins. The cholangiocyte 2-D protein pattern is
      markedly different from that of isolated rat hepatocytes or whole rat liver, with
      high levels of proteins previously known to be expressed by cholangiocytes (e.g.,
      cytokeratins, actins) as well as protein not previously demonstrated to be
      expressed at high levels (e.g., annexin V, selenium binding protein). We conclude
      that this cholangiocyte-derived, 2-D protein map will be a crucial resource for
      studies directed at our understanding of cholangiocyte physiology and
      pathobiology.

PMID- 9932817
TI  - Two-dimensional electrophoretic analysis of membranous protein from human thyroid
      tissues and cancer cell lines.
AB  - Thyroid neoplasm is the most commonly encountered neoplastic disorder in
      endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration
      cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule
      from a benign lesion. There are certain limitations and pitfalls in FNAC,
      especially in the diagnosing of follicular tumors. The lack of characteristic
      findings or a specific tumor marker are the most common problems in the
      preoperative diagnosis of thyroid follicular carcinoma. Although serum
      thyroglobulin level has been used as a tumor marker for post-operative, well
      differentiated thyroid cancer, the assay cannot be used for preoperative
      diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer
      cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used
      for the investigation of tumor markers. Specific spots were identified in the
      area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the
      CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic
      thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa
      with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This
      spot appeared to be a tumor marker of follicular cancer cells. This spot could
      not be found in the papillary and anaplastic cancer cell lines and other benign
      thyroid tissues. Specific proteins that were identified in this study may be
      useful as tumor markers for follicular thyroid carcinoma.

PMID- 9932818
TI  - Mapping and identification of Corynebacterium glutamicum proteins by two
      dimensional gel electrophoresis and microsequencing.
AB  - As a prerequisite for proteome analyses of Corynebacterium glutamicum separation
      of the cytoplasm and the membrane fraction was optimized and two-dimensional (2
      D) gel electrophoresis was established. The resulting 2-D protein maps revealed
      over 1000 silver-stained protein spots separated by isoelectric point and
      molecular mass for cytoplasmic proteins and approximately 700 silver-stained
      spots for proteins of the membrane fraction. Proposing a mean size of 1 kbp per
      gene the complete C. glutamicum genome of 3 Mbp encodes 3000 different proteins;
      more than half of these can be located using the maps which are presently
      available. In this study 10 proteins were identified by N-terminal
      microsequencing, namely the 35 kDa antigen, antigen 84, ATP synthase subunits
      alpha, gamma and delta, cysteine synthase, elongation factor G and Ts, enolase,
      and rotamase. For seven sequences, corresponding proteins could not be
      identified. Additionally, two proteins were specifically detected by
      immunoblotting, a corynebacterial porin and the cytoplasmic protein threonine
      dehydratase. The methods and 2-D maps established in this study will be the basis
      for comparative studies of protein expression and a detailed proteome analysis of
      C. glutamicum.

PMID- 9932819
TI  - Protein patterns of human nasal and bronchoalveolar lavage fluids analyzed with
      two-dimensional gel electrophoresis.
AB  - We have previously described the protein patterns of human nasal lavage fluid
      (NLF) and bronchoalveolar lavage fluid (BALF) after two-dimensional gel
      electrophoresis (2-DE). We now report the identification of a number of
      additional proteins in these 2-DE patterns. Several plasma proteins (alpha2
      macroglobulin, haptoglobin alpha1-chain, IgA S chain, ceruloplasmin, alpha1
      microglobulin, amyloid P and apolipoprotein A-1) could be included both in the
      BALF and NLF spot pattern data bases by matching with a master plasma 2-DE
      pattern (SWISS-2DPAGE). Furthermore, lysozyme, lactoferrin and the
      antiinflammatory proteins lipocortin-1 and Clara cell protein 16 (CC-16) were
      identified by matching with reference proteins and Western immunoblots.
      Significant differences in the levels of some of the identified proteins were
      found between NLF and BALF, and between BALF from smokers and nonsmokers.
      Transferrin, hemopexin and haptoglobin alpha1 were lower in NLF than BALF, while
      IgA, lysozyme and lactoferrin were higher in NLF than BALF. One form of alpha1
      microglobulin was more abundant in NLF than in BALF, while the opposite was found
      for a second form of the same protein. Moreover, the levels of IgA, ceruloplasmin
      and the pro-form of apolipoprotein A-1 in BALF were lower in smokers than in
      nonsmokers. The possibility to describe and analyze differences in NLF and BALF 2
      DE patterns at the protein spot level may have wide clinical applications.

PMID- 9932820
TI  - Insulin resistance syndrome: options for treatment.
AB  - BACKGROUND: Insulin resistance is characterized by impaired responsiveness to
      endogenous or exogenous insulin. Loss of responsiveness is associated with a
      "clustering" of cardiovascular risk factors that includes abdominal obesity,
      hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia; this
      association is referred to as the insulin resistance syndrome (IRS). METHODS: We
      searched MEDLINE, using the term insulin resistance, and reviewed relevant
      publications. RESULTS: We review the mechanisms and clinical consequences
      attributed to IRS, along with patient assessment and treatment options.
      CONCLUSIONS: It is possible to improve insulin sensitivity by caloric
      restriction, weight loss, exercise, and drug therapy. Metformin and troglitazone,
      approved for use in the treatment of type 2 diabetes mellitus (DM), improve
      insulin sensitivity and lower plasma glucose concentrations. Several other
      medications that may improve insulin sensitivity are currently under clinical
      investigation. Studies are needed to determine the effect of these medications on
      morbidity and mortality of patients with insulin resistance and type 2 DM.

PMID- 9932821
TI  - Automation of clinical and patient records.
AB  - BACKGROUND: With advances in computer technology and mounting pressure to cut
      health care costs, there is a desire to automate clinical and patient records.
      METHODS: We reviewed the barriers that hindered automation in the past, changes
      in the business environment, and the recent developments that could encourage
      automation, including the enactment of the Health Insurance Portability and
      Accountability Act (HIPAA). RESULTS: Although conditions for automation have
      improved, significant barriers remain, including variation in state laws, lack of
      comprehensive data to assure return on automation investment, and most
      importantly, lack of clinical data and record-keeping standards. CONCLUSIONS:
      Congress needs to enact HIPAA follow-up legislation that addresses the legal and
      standards issues. To minimize the risks for automation, institutions are advised
      to take a buy-a-little, test-a-little, and fix-a-little approach.

PMID- 9932822
TI  - Aspirin administration for cardiac-related acute chest pain/angina: increased use
      in Medicare patients.
AB  - BACKGROUND: Coronary heart disease (CHD), the leading cause of death in the
      United States, accounted for approximately 490,000 deaths in 1993. Angina
      pectoris, a manifestation of CHD, accounted for 13,586 Medicare discharges in
      1993 in Texas. A pilot project showed aspirin prophylaxis that reduces
      cardiovascular morbidity and mortality in individuals with acute angina is
      underused. Texas Medical Foundation collaborated with 10 acute-care facilities to
      improve aspirin prophylaxis. METHODS: Collaborators assessed processes of care
      and implemented clinical pathways to improve aspirin administration. Data were
      abstracted from medical records before and after pathway implementation to
      evaluate impact. RESULTS: Aspirin administration during hospital stay increased
      10.8%, aspirin administration on discharge increased 11.7%, and average time from
      arrival to aspirin administration decreased 2.9 hours. CONCLUSIONS: Results
      suggest collaborator-implemented clinical pathways significantly improved care
      received by Medicare patients admitted for cardiac-related acute chest
      pain/angina. Data suggest room for further improvement.

PMID- 9932823
TI  - Stroke in Hispanic veterans: a descriptive study.
AB  - BACKGROUND: Differences in risk factor prevalence and distribution of
      atherosclerotic cerebrovascular disease have been reported among different racial
      ethnic groups. Identification of stroke syndromes and risk factors specific to
      the Puerto Rican male population should lead to more effective diagnosis,
      treatment, and prevention programs. METHODS: We prospectively and consecutively
      evaluated 118 Hispanic male veterans admitted to our Stroke Unit from June 1994
      to September 1995. RESULTS: Ninety patients (76%) had an ischemic infarct, 26
      (22%) had a transient ischemic attack, and 2 (2%) had an intracerebral and/or
      subarachnoid hemorrhage. Hypertension was the most common risk factor.
      Echocardiographic studies were done in 64% of the patients, and the most common
      findings were concentric left ventricular hypertrophy and diastolic dysfunction.
      Cerebral angiography was done in 40 cases, and findings were abnormal in 32
      (80%). CONCLUSIONS: We believe this is the largest descriptive study of Hispanic
      male veterans with stroke syndromes. It provides baseline data to serve as a
      comparison group for future research.

PMID- 9932824
TI  - Clinical study of mitral valve repair: short-term and long-term outcomes.
AB  - BACKGROUND: In recent years, mitral valve reconstructive techniques have become
      an increasingly preferential alternative to replacement. The purpose of this
      study was to evaluate short-term and long-term outcomes associated with mitral
      valve repair. METHODS: This study involved 99 patients who had mitral valve
      repair for mitral regurgitation from January 1990 to June 1996. Short-term and
      long-term outcomes evaluated included mortality, clinical complications,
      readmissions, valve deterioration, reoperation, thromboembolism, endocarditis,
      functional heart class, and health perception. RESULTS: Overall mortality was
      18%, which included 11 operative deaths and 7 late deaths. Ischemic valve disease
      and NYHA class III and IV were significant predictors of early and late
      mortality. Overall 5-year survival was 79%. Freedom from all valve-related morbid
      events was 90% at 5 years. CONCLUSIONS: Functional heart class and etiology of
      valve disease are the most important indicators of overall survival and
      morbidity. Transesophageal echocardiography should be used to evaluate the
      adequacy of repair.

PMID- 9932825
TI  - Prevalence of previous appendectomy among patients needing gastrointestinal
      endoscopy.
AB  - BACKGROUND: The appendix may be an immune modulator of the gut, and its absence
      may lead to an increase in gastrointestinal illnesses. If this is true, we may
      expect patients needing endoscopy to have a higher prevalence of previous
      appendectomy. METHODS: We did a case-control study at the University of Oklahoma
      Hospital for 13 months. Subjects having endoscopic evaluation at the University
      of Oklahoma Hospital formed the study group. Patients seen at the general
      medicine clinic of the University of Oklahoma served as controls. We recorded the
      patient's name, age, sex, race, history of smoking, and history of appendectomy
      or tonsillectomy. RESULTS: The endoscopy group had 524 patients; 469 patients
      were in the control group. There were no differences based on race or history of
      smoking. There was greater prevalence of previous appendectomy in the endoscopy
      group (33.46% vs. 20.55%). The prevalence of tonsillectomy was 29.28% in the
      study group vs. 21.61% among the controls. Multiple regression revealed that
      history of appendectomy and not tonsillectomy was related to the performance of
      endoscopy. CONCLUSION: History of appendectomy is associated with greater
      performance of endoscopy.

PMID- 9932826
TI  - Causes and outcome of upper and lower gastrointestinal bleeding: the Grady
      Hospital experience.
AB  - BACKGROUND: Gastrointestinal (GI) bleeding remains a common medical condition,
      with a mortality rate believed to have remained unchanged over the past five
      decades. METHODS: Over a 50-month period, the gastroenterology consultative
      service at a large inner-city hospital prospectively evaluated acute upper GI
      (UGI) bleeding or lower GI (LGI) bleeding in consecutive patients. A number of
      clinical variables were recorded at admission on a standardized data collection
      form. The cause of bleeding was determined in most patients by endoscopic
      examination. RESULTS: Of the 796 patients assessed for UGI bleeding, 727 (91%)
      had upper endoscopy. The most common causes of UGI bleeding were gastric ulcer
      (32%), duodenal ulcer (28%), esophageal varices (9%), and Mallory-Weiss tear
      (6%). The rebleeding rate was 14% and 20% of patients had endoscopic therapy.
      Surgical therapy for bleeding was required in 7% of patients. Of the 165 patients
      assessed for LGI bleeding, 150 (91%) had colonoscopy. Colonic diverticulosis was
      considered etiologic in 56% of patients, followed by colonic ulcers in 10%,
      carcinoma in 7%, and vascular ectasias in 5%. The rebleeding rate in these
      patients was 20%, and surgical therapy for bleeding was required in 10%. The
      overall mortality for patients with UGI bleeding was 9% and was independently
      associated with portal hypertension and rebleeding. In contrast, the mortality
      rate for LGI bleeding was 4%, and there was little power to determine significant
      factors associated with death. CONCLUSIONS: The causes of gastrointestinal
      bleeding remain little changed over the past several decades, though in our large
      series the need for surgical therapy and the mortality from both upper and lower
      GI bleeding were low.

PMID- 9932827
TI  - Prescribing controlled substances in Tennessee: progress, not perfection.
AB  - BACKGROUND: In the 1980s, Tennessee ranked among the top 10 states in per capita
      consumption of several controlled substances. We describe efforts designed to
      reduce non-criminally motivated misprescribing in Tennessee, present Tennessee's
      recent Drug Enforcement Administration (DEA) rankings, and suggest how physicians
      may reduce misprescribing. METHODS: Tennessee's Board of Medical Examiners (BME)
      consults with Tennessee Physician Health Program (PHP) and refers selected
      physicians to a continuing medical education (CME) program offered at Vanderbilt
      University School of Medicine. The BME has also published a clear set of
      prescribing guidelines. RESULTS: Of more than 160 CME participants, only two have
      reappeared before the BME for prescribing infractions. Tennessee's overall DEA
      ranking improved from 7th highest to 17th from 1994 to 1997. CONCLUSIONS: The
      reasons the rankings improved cannot be established, but the changes occurred at
      the same time as the BME, PHP, and Vanderbilt CME collaborations. We will
      continue to promote professional and patient health throughout the region.

PMID- 9932828
TI  - Successful treatment of widely disseminated acanthamoebiasis.
AB  - Disseminated Acanthamoeba infections are almost invariably fatal, with no
      universally accepted standard for treatment. Reports of acanthamoebiasis in non
      human-immunodeficiency-virus infected hosts are rare. We successfully treated a
      lung transplant patient who had disseminated acanthamoebiasis using a combination
      of pentamidine, 5-fluorocytosine, itraconazole, and topical chlorhexidine
      gluconate/ketoconazole cream.

PMID- 9932829
TI  - Exudative eosinophilic pleural effusion due to Strongyloides stercoralis in a
      diabetic man.
AB  - A 61-year-old diabetic man had fever and a significant exudative type of
      eosinophilic pleural effusion. Microscopic examination of stained specimens of
      bronchial washings revealed filariform larvae of Strongyloides stercoralis. This
      intestinal nematode is endemic in some areas of the world. Pulmonary symptoms are
      usually mild, though severe pulmonary involvement may be occasionally seen.
      Although serohemorrhagic pleural effusion has been well reported in the
      literature, we found no report of such an unusual case of significant exudative
      eosinophilic pleural effusion due to strongyloidiasis.

PMID- 9932830
TI  - AIDS-related Kaposi's sarcoma involving bone and bone marrow.
AB  - AIDS-related Kaposi's sarcoma rarely involves bone or bone marrow. Computed
      tomography of the abdomen and pelvis of an AIDS patient with lower back pain and
      bilateral limb edema revealed multiple lesions involving liver, spleen, and axial
      skeleton. Bone marrow examination of the involved iliac crest revealed Kaposi's
      sarcoma. Pathologic diagnosis is important so that appropriate treatment can be
      prescribed.

PMID- 9932831
TI  - Cryptogenic mycotic aneurysm of the right coronary artery.
AB  - A 61-year-old man with chest pain and fever was referred to our hospital. The
      physical examination and electrocardiogram were unrevealing. Laboratory tests
      showed leukocytosis, and echocardiography showed mild pericardial effusion. The
      patient died soon after hospital admission. Necropsy revealed ruptured mycotic
      aneurysm of the right coronary artery in the absence of infective endocarditis.
      Thus, mycotic aneurysm of the coronary artery may occur without infective
      endocarditis and may be clinically manifested as pericarditis and leukocytosis.

PMID- 9932832
TI  - Acquired lymphangiectasis.
AB  - Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as
      a complication of surgical intervention and radiation therapy for malignancy.
      Acquired lymphangiectasis shares clinical and histologic features with the
      congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these
      vesiculo-bullous lesions is important because they may be associated with pain,
      chronic drainage, and cellulitis. We describe two patients who had these lesions
      after treatment for cancer and review the pertinent literature. Although a number
      of treatment options are available, we have found CO2 laser ablation particularly
      effective.

PMID- 9932833
TI  - Cat-scratch disease causing status epilepticus in children.
AB  - Status epilepticus from cat-scratch encephalopathy is often recalcitrant to usual
      therapies, causing treatment to focus on critical care management of the patient
      that may require aggressive interventions, such as continuous pentobarbital
      administration. We describe two children whose initial clinical presentation of
      cat-scratch disease was status epilepticus with normal cerebrospinal fluid
      studies. A history of cat exposure (specifically, kitten and/or fleas), regional
      lymphadenopathy, and a papule or inoculation site should be sought, but are not
      essential for diagnosis. The presumptive diagnosis of cat-scratch disease can be
      made by serology alone even in the absence of classic diagnostic criteria. Our
      two cases and other reports in the literature show a favorable prognosis in most
      cases, despite the occurrence of status epilepticus. The diagnosis of cat-scratch
      disease should be strongly considered in all children with unexplained status
      epilepticus or encephalopathy and serologic testing for Bartonella henselae
      should be done.

PMID- 9932834
TI  - Marked prolongation of the succinylcholine effect two hours after neostigmine
      reversal of neuromuscular blockade in a patient with chronic renal insufficiency.
AB  - Prolonged neuromuscular blockade from succinylcholine after neostigmine
      administration has been reported in patients with frank renal failure. We present
      a case of prolonged neuromuscular blockade from succinylcholine administration,
      given 2 hours after neostigmine reversal of neuromuscular blockade in a patient
      with chronic renal insufficiency. This case shows that patients with chronic
      renal insufficiency, like patients with renal failure, are at risk for prolonged
      succinylcholine blockade if they have recently received anticholinesterase
      reversal of neuromuscular blockade. Administration of succinylcholine for
      facilitation of urgent endotracheal intubation may be required soon after
      reversal of nondepolarizing muscle relaxants, particularly in patients who return
      to the operating room for emergency care.

PMID- 9932835
TI  - Mycobacterium avium infection in a patient with the acquired immunodeficiency
      syndrome and silicone breast implants.
AB  - We describe a case of Mycobacterium avium-intracellulare infection in a silicone
      augmented breast of a female patient with the acquired immunodeficiency syndrome
      and disseminated Mycobacterium avium complex. Explantation and treatment with
      appropriate antibiotics led to resolution of the breast infection.

PMID- 9932836
TI  - Uterine rhabdomyosarcoma metastatic to mediastinal lymph nodes: diagnosis by
      transbronchial needle aspiration.
AB  - Uterine rhabdomyosarcoma is rare, with only 60 reported cases. We describe an
      asymptomatic patient with metastatic uterine rhabdomyosarcoma manifested as
      extensive mediastinal lymphadenopathy. This 73-year-old woman had been previously
      treated for endometrial rhabdomyosarcoma and was referred to us when a right
      hilar density was seen on a chest radiograph; computed tomography showed a nodule
      in the right upper lobe and extensive right hilar and subcarinal lymphadenopathy.
      The diagnosis of metastatic rhabdomyosarcoma was made by fiberoptic bronchoscopy
      using transbronchial needle aspiration (TBNA). The patient is well 11 months
      after completing five cycles of chemotherapy. This is the first reported case of
      uterine rhabdomyosarcoma with metastasis to the mediastinum and the first case
      diagnosed with TBNA, which avoided the need for an invasive diagnostic procedure.

PMID- 9932837
TI  - Unraveling obesity.

PMID- 9932838
TI  - The future of pediatric transplantation.

PMID- 9932839
TI  - Pediatric endoscopy skills: are numbers important?

PMID- 9932840
TI  - Genetic cholestasis syndromes.

PMID- 9932841
TI  - Serodiagnosis of Helicobacter pylori in pediatric patients.

PMID- 9932842
TI  - Can Crohn's (at first) be only skin deep?

PMID- 9932843
TI  - Sacrosidase therapy for congenital sucrase-isomaltase deficiency.
AB  - BACKGROUND: The purpose of this study was to determine if sacrosidase, a liquid
      produced from Saccharomyces cerevisiae containing 6000 IU of sucrase activity per
      mg protein, prevented symptoms of diarrhea, abdominal cramps, gas, and bloating
      in patients with congenital sucrase-isomaltase deficiency (CSID) consuming a
      normal sucrose and carbohydrate-containing diet. METHODS: Twenty-eight children
      (aged 5 months to 11 years) underwent a randomized, double-blind trial consisting
      of two phases: 1) three sucrose breath H2 tests with three single-dose treatments
      (placebo, sacrosidase, and sacrosidase plus milk), and 2) a dose-response phase
      consisting of four multidose treatments, each for 10 days of full-strength
      sacrosidase, 1:10 dilution, 1:100 dilution, and 1:1000 dilution. Patients who
      weighed less than or equal to 15 kg received a dose of sacrosidase and those who
      weighed more than 15 kg received 2 ml. For the dose-response phase each patient
      consumed a normal diet. The number of stools and severity of symptoms were
      recorded daily for each concentration of sacrosidase administered and compared to
      a baseline period during which the patient took no sacrosidase and consumed a
      sucrose/starch-free diet. Data were analyzed using an ANOVA model and the
      nonparameter Wilcoxon signed-rank test. RESULTS: Breath H2 excretion decreased
      significantly when patients received sacrosidase or sacrosidase plus milk
      compared to placebo during sucrose breath tests. During the dose-response phase
      significant treatment differences were observed between the two higher
      concentrations and the two lower concentrations of sacrosidase for both total
      stools (p < 0.001) and total symptom score (p = 0.003). Higher concentrations of
      sacrosidase were associated with fewer stools and a greater number of formed or
      hard stools compared to lower concentrations and compared to the baseline period.
      Higher concentrations were also associated with fewer symptoms of gas, abdominal
      cramps, or bloating, but no differences in vomiting. The only significant adverse
      event was wheezing in one child with a history of asthma. CONCLUSIONS:
      Sacrosidase is a safe, effective, well-accepted treatment to prevent
      gastrointestinal symptoms in patients with CSID consuming a normal diet.

PMID- 9932844
TI  - Helicobacter pylori infection in children with celiac disease: prevalence and
      clinicopathologic features.
AB  - BACKGROUND: Celiac disease is frequently associated with chronic gastritis.
      Helicobacter pylori is the main etiologic agent of chronic gastritis. The aim of
      this study was to assess the prevalence of H. pylori, the related symptoms, and
      the endoscopic and histologic gastric features in children with celiac disease.
      METHODS: Eight-one (24 boys, 57 girls; age range: 1.4-17.7 years, median 6.8)
      children with celiac disease were studied. All children had a blood sample taken.
      In a subgroup of 30 children who underwent endoscopy, three gastric biopsy
      specimens were taken for histology (hematoxylin and eosin, Giemsa,
      immunohistochemistry) and urease quick test. Symptom complaints were recorded.
      Age- and sex-matched (one case, one control) children without celiac disease were
      used for comparison. Serum H. pylori IgG were measured by means of a locally
      validated commercial enzyme-linked immunoassay. RESULTS: Overall, 15 of 81
      (18.5%) children with celiac disease and 14 of 81 (17.3%) control children were
      positive for H. pylori. The percentage of H. pylori positivity was similar in
      children with untreated and treated celiac disease. Recurrent abdominal pain was
      the only symptom that helped to distinguish between H. pylori-positive and H.
      pylori-negative children. However, symptoms disappeared in patients with celiac
      disease after gluten withdrawal, irrespective of H. pylori status. All endoscopic
      (erythema, nodularity) and histologic (superficial-, interstitial-, lymphocytic
      gastritis, activity, lymphoid follicles) findings did not differ between celiac
      and nonceliac H. pylori-positive children. CONCLUSIONS: Prevalence and clinical
      expressivity of H. pylori infection is not increased in children with celiac
      disease. The clinicopathologic pattern of the infection is not specifically
      influenced in this condition.

PMID- 9932845
TI  - Lymphocyte subset profile of young healthy children residing in a rural area:
      possible role of recurrent gastrointestinal infections.
AB  - BACKGROUND: Lymphocyte subsets in healthy children are currently characterized by
      age-related standards. Because antigenic stimuli play a role in maturation of the
      immune system after birth, there is a question of whether cellular immune
      development differs in infants whose living conditions entail extensive antigenic
      exposure and infants growing up in a more protected environment. METHODS:
      Peripheral blood lymphocyte subsets were studied in two populations of children
      of similar age and nutritional status; children belonging to a rural population
      residing in proximity with farm animals and children from an economically
      privileged urban population. In each population, children studied included a
      group with an acute diarrheal episode and a healthy control group. RESULTS: Among
      rural population children, 65% had experienced at least one episode of
      gastroenteritis within the previous 3-month-period, compared with less than 10%
      of urban population children. In the rural population group 15% had experienced
      two or more episodes of gastroenteritis. The proportion of helper T cells was
      similar in rural population and urban population children. Among helper T cells,
      the proportion of CD29+ "memory" cells of the total CD4+ helper T cells was more
      than two times higher than those in rural population children. The proportion of
      CD8 cells was higher in rural population children than in urban population
      children, and the proportion of natural killer cells, CD56+ and CD57+, was two to
      three times higher in rural population children. Within each population,
      peripheral blood lymphocyte subsets did not differ between the healthy control
      group and those with acute diarrhea. CONCLUSIONS: In young children exposure to
      environmental pathogens and specifically to gastrointestinal antigenic stimuli is
      a major factor affecting development of the cellular immune response. Young
      children who have experienced enhanced infectious exposure have a peripheral
      blood lymphocyte profile similar to that of adults.

PMID- 9932846
TI  - Home parenteral nutrition in children: the Polish experience.
AB  - BACKGROUND: Home parenteral nutrition has become routine for management of
      intestinal failure in patients. In Poland the main obstacle to widespread use of
      home parenteral nutrition is the lack of interest of commercial companies in
      delivering feedings and ancillaries to patients. METHODS: Twenty-five home
      parenteral nutrition patients aged from 4 months to more than 13 years were
      reviewed. The mother or both parents were trained in home parenteral nutrition
      techniques for 4 to 6 weeks and compounded the nutrients themselves at home.
      RESULTS: The mean duration of home parenteral nutrition was 10,117 patient days.
      Hospital stays of patients receiving parenteral feedings were significantly
      shorter than the duration of administration of home parenteral nutrition (p <
      0.001). Eleven children are continuing the home parenteral nutrition program.
      Eighty-three catheters were used in these patients. The rate of catheter
      occlusion decreased within the observation period, and in 1997 not one case of
      occlusion was observed. In 1997 only three catheters were removed during 7.8
      patient years, and the overall incidence of catheter-related complications was
      0.38 per patient year. The overall occurrence of septicemia was one case in 516
      days and of catheter infection was one in 459 days. In 1997 a catheter was
      infected on average of once every 1419 days. There was significant improvement in
      the z score for weight during therapy. The average monthly cost of nutrients and
      ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs
      are 1.6 to 3 times lower than those recorded in other studies. CONCLUSION: Home
      parenteral nutrition in children with nutrients mixed by caregivers in the home
      setting is a safe and appropriate method of treatment that can be used in
      countries where home parenteral nutrition solutions are not manufactured or where
      commercial home parenteral nutrition is not economically feasible.

PMID- 9932848
TI  - Normal ranges of 24-hour pH-metry established in corrected esophageal atresia.
AB  - BACKGROUND: This study was undertaken to determine baseline values of 24-hour pH
      metry in children who had undergone correction for esophageal atresia. METHODS: A
      24-hour pH-metry without medication was conducted in 13 patients with an
      uncomplicated postoperative course after correction of esophageal atresia. The pH
      metry was performed in the hospital with a flexible glass electrode. RESULTS: The
      mean reflux index was 4.08%, the mean total number of reflux periods with a pH
      less than 4 was 21, and the mean number of periods of pH less than 4 lasting
      longer than 5 minutes was 2.5. CONCLUSIONS: Twenty-four-hour pH-metry values in
      asymptomatic esophageal atresia patients are the same as in children from the
      same age group with normal anatomy.

PMID- 9932847
TI  - Evaluation of enzyme-linked immunosorbent assay for the diagnosis of Helicobacter
      pylori infection in children from different age groups with and without duodenal
      ulcer.
AB  - BACKGROUND: Although enzyme-linked immunosorbent assay (ELISA) is highly
      sensitive and specific for the diagnosis of Helicobacter pylori infection in
      adults, their performance in children is still controversial. METHODS: A second
      generation ELISA was used to evaluate the IgG response to H. pylori in the serum
      of 130 consecutive children who underwent upper gastrointestinal endoscopy. The
      presence of H. pylori was determined in antral biopsy specimens by culture,
      urease test, and histologic analysis. RESULTS: Sixty-eight children (all of the
      20 who had duodenal ulcer) were H. pylori positive by microbiologic test.
      Immunoglobulin G antibodies to H. pylori were detected in 79.4% of the infected
      children and in 8.1% of the noninfected ones. The sensitivity of the test was
      higher in patients with duodenal ulcer (100%) than in those without (70.8%). When
      used in children of different ages the test also presented differences in
      sensitivity: 44.4% in children 2 to 6 years old; 76.7% in children 7 to 11 years
      old, and 93.1% in children 12 to 16 years old (p = 0.006). The serum
      immunoglobulin G concentration was significantly higher (p = 0.0003) in children
      with duodenal ulcer than in those without and was higher in older children than
      in younger ones without duodenal ulcer (p = 0.05). CONCLUSIONS: The accuracy of
      the test in children with duodenal ulcer and in children more than 12 years old
      was good; however, in children up to 12 years of age without duodenal ulcer, the
      sensitivity of the test was too low to be used for screening purposes or to rule
      out the presence of infection.

PMID- 9932849
TI  - Increased concentrations of eosinophilic cationic protein in whole-gut lavage
      fluid from children with inflammatory bowel disease.
AB  - BACKGROUND: Eosinophils may be involved in the pathogenesis of inflammation in
      inflammatory bowel disease. The purpose of this study was to verify whether
      concentrations of eosinophilic cationic protein in gut lavage fluid from children
      with inflammatory bowel disease correlate with clinical and laboratory indexes of
      disease activity. METHODS: Twenty-three children with Crohn's disease, 14 with
      ulcerative colitis, and 22 age-matched control subjects entered the study.
      Radioimmunoassay and sandwich enzyme-linked immunosorbent assay techniques were
      used to measure eosinophilic cationic protein, total immunoglobulin G and
      interleukin-1beta, respectively. RESULTS: Gut lavage eosinophilic cationic
      protein levels were significantly (p < 0.005) higher in patients with Crohn's
      disease and ulcerative colitis than in control subjects. Intestinal eosinophilic
      cationic protein levels decreased in three of four children with Crohn's disease
      who were fed an elemental diet. There was a significant (p < 0.001) correlation
      between eosinophilic cationic protein concentrations and immunoglobulin G and
      interleukin-1beta levels in gut lavage fluid. CONCLUSIONS: Elevated intestinal
      eosinophilic cationic protein levels in inflammatory bowel disease suggest that
      eosinophils are involved in the gastrointestinal inflammation in this disease.
      Intestinal eosinophilic cationic protein concentration is another marker with
      which to discriminate between active and inactive inflammatory bowel disease.

PMID- 9932850
TI  - Diet and chronic constipation in children: the role of fiber.
AB  - BACKGROUND: Chronic constipation is one of the most common disorders in Western
      countries and despite numerous clinical, pathophysiologic, and epidemiologic
      studies its cause is still unclear. Several hypotheses have been proposed and
      according to experimental studies and clinical observation, fiber intake could
      play a role in its pathogenesis. The purpose of this case-control study was to
      examine the possible correlation of idiopathic chronic constipation in children
      and dietary intake, particularly fiber intake. METHODS: A randomized sample of
      children (291 children with constipation and 1602 controls) aged 2 to 14 years
      was taken from three of the 52 counties of Greece. Stratification was performed
      on the basis of urban, rural, or suburban location and socioeconomic status. The
      nutritional data were obtained from a 3-day dietary record and a dietary history.
      Statistical analysis was performed with multivariate tests, multivariate analysis
      of variance, discriminant analysis, and chi-square analysis according to the
      characteristics of the correlated variables. RESULTS: Constipated children had a
      lower caloric and nutrient intake (p < 0.001), lower body weight/height (p <
      0.001), and higher prevalence of reported anorexia (p < 0.001). Discriminant
      analysis indicated that dietary fiber alone was independently negatively
      correlated with chronic constipation, despite the age and the age of onset of
      constipation. Relative risk also had a negative correlation with fiber intake (p
      < 0.001). Of the main fiber fractions only cellulose and pentose were
      independently correlated with chronic constipation. CONCLUSIONS: Lack of fiber
      may play an important role in the etiology of chronic idiopathic constipation in
      children.

PMID- 9932851
TI  - Symptomatic colonic polyps in childhood: not so benign.
AB  - BACKGROUND: The clinical spectrum of symptomatic polyps and the frequency of
      familial polyposis is not well defined in children. In the present study, a
      series of children with juvenile polyposis coli (JPC) and non-JPC polyps were
      studied. METHODS: Children with symptomatic colonic polyps and negative family
      history of polyps were ascertained by review of endoscopic records. Juvenile
      polyposis coli was defined as 10 or more juvenile polyps or any juvenile polyp in
      a relative of an index case of JPC. Polyps were tested for Ki-ras mutations, p53
      overexpression, and aneuploidy. RESULTS: Seventy-eight children (age range, 0.4
      18 years) were identified, all evaluated for lower gastrointestinal bleeding.
      Nine (12%) had JPC, 66 (84%) had isolated juvenile polyps, and 3 (4%) had other
      types of polyps. The JPC and non-JPC groups were similar in age (p = 0.4) and
      symptom duration (p = 0.3). The JPC group had more polyps (p = 0.0001), and
      greater likelihood of anemia (p = 0.01), polyps with adenomatous change (p =
      0.03), and right-colon polyps (p = 0.001). In three of eight JPC families, polyps
      were identified in asymptomatic first-degree relatives. No abnormalities in Ki
      ras, p53, or aneuploidy were identified. CONCLUSIONS: Juvenile polyposis coli is
      common in children with symptomatic polyps, and is associated with anemia, right
      colon polyps, and adenomas. The risk of polyps and of colorectal cancer in
      relatives of persons with JPC requires further study.

PMID- 9932852
TI  - Findings on routine abdominal ultrasonography in cystic fibrosis patients.
AB  - BACKGROUND: Right lower quadrant abdominal pain may pose a diagnostic problem in
      patients with cystic fibrosis. Abdominal ultrasound examination, used commonly in
      the diagnostic work-up, may reveal abnormalities of the appendix. However,
      interpretation of such findings is problematic, because the appearance of the
      gastrointestinal system during routine examination has not been documented in
      patients with cystic fibrosis. The purpose of this study was to investigate the
      findings during routine abdominal ultrasound scans in our cohort of patients with
      cystic fibrosis and in control subjects. METHODS: Abdominal ultrasound scans were
      performed prospectively during routine clinic visits in a cohort of patients with
      cystic fibrosis. RESULTS: Fifty patients aged 10+/-6 years, (range, 0.5-28 years)
      were examined; 45 had pancreatic insufficiency. Four patients (3 with pancreatic
      insufficiency) reported right lower quadrant pain at the time of the scan.
      According to standard ultrasound criteria, the appearance of the appendix was
      abnormal in 8 patients (16%), 6 had a mucoid appendix, and 2 had a pathologically
      thickened appendiceal wall. Only 1 of these 8 patients mentioned abdominal pain
      at the time of the study. Other incidental findings included gallstones (3
      patients), intussusception (2 patients), and pancreatic cyst (1 patient).
      CONCLUSIONS: Abnormalities can be observed during routine abdominal
      ultrasonographic studies in cystic fibrosis. These findings may not be associated
      with abdominal pain; their clinical relevance needs further investigation.

PMID- 9932853
TI  - A high index of suspicion: the key to an early diagnosis of Wilson's disease in
      childhood.
AB  - BACKGROUND: To study the clinical features of Wilson's disease in childhood.
      METHODS: Retrospective review of the clinical, laboratory, and histologic
      features and prognosis of Wilson's disease in 26 Spanish children. RESULTS: The
      first medical visit, at age 9.8+/-3.4 years (range, 4-16 years), was prompted by
      liver dysfunction detected accidentally (61%), symptoms of liver disease (27%),
      family screening (8%), and extrapyramidal symptoms and personality changes (4%).
      There were laboratory data of hepatic failure in 27%. All copper metabolism test
      results (total serum copper, 24-hour urine excretion, serum ceruloplasmin) were
      abnormal in 62%, two in 27%, and one in 11%. All patients in whom extrahepatic
      involvement was found at diagnosis had severe liver disease. Histologic findings
      were portal fibrosis with steatosis (29%), cirrhosis (21%), portal fibrosis
      (17%), chronic active hepatitis (17%), and minimal changes or normality (17%).
      Penicillamine was administered to all but one patient. Four children underwent
      liver transplantation, three of them having received penicillamine for 12, 45,
      and 70 days. Three other patients recovered from liver failure after 1 year of
      treatment with penicillamine. After a follow-up of 4.5+/-3.3 years, all the
      children survived. Penicillamine caused severe toxicity in one patient.
      CONCLUSIONS: Wilson's disease in childhood is generally detected by maintaining a
      high suspicion of liver disease in patients who have no or nonspecific hepatic
      symptoms. Kayser-Fleischer ring is rare in childhood. Drug therapy is effective
      and well tolerated, even in some cases of hepatic insufficiency.

PMID- 9932854
TI  - Intestinal barrier function and cow's milk sensitization in guinea pigs fed milk
      or fermented milk.
AB  - BACKGROUND: The respective effect of milk and fermented milks on intestinal
      barrier capacity and on sensitization to beta-lactoglobulin was studied using a
      guinea pig model of cow's milk allergy. METHODS: Guinea pigs were fed a control
      diet or the same diet supplemented with milk, fermented milk (Streptococcus
      thermophilus and Bifidobacterium breve), or dehydrated fermented milk. Intestinal
      barrier capacity to macromolecules was assessed in an Ussing chamber, and
      sensitization to cow's milk proteins was measured by systemic anti-beta
      lactoglobulin immunoglobulin G1 titers and by intestinal anaphylaxis, the latter
      assessed by the beta-lactoglobulin-induced increase in short-circuit current of
      jejunal fragments (deltaIsc(beta-LG)). RESULTS: The electrical resistance of
      jejunum was similar in the four groups (approximately 80 omega/cm2) suggesting
      the same paracellular permeability. The transport of 14C-beta-lactoglobulin from
      mucosa to serosa was significantly decreased in the animals fed dehydrated
      fermented milk (403+/-131 ng / hr x cm2) compared with that in control animals or
      animals fed milk (767+/-250 ng / hr x cm2 and 749+/-475 ng / hr x cm2,
      respectively; p < 0.05). Milk fermentation did not modify native beta
      lactoglobulin concentration but anti-beta-lactoglobulin immunoglobulin G1 titers
      were higher in fermented milk and dehydrated fermented milk (log10 titer = 2.86
      and 2.79, respectively) than in guinea pigs fed milk (log10 titer = 2.5; p <
      0.007). However, beta-lactoglobulin-induced intestinal anaphylaxis remained the
      same in the three groups (deltaIsc(beta-LG), 9.6+/-4.1 microA/cm2, 8.5+/-4.3
      microA/cm2, and 8.5+/-3.4 microA/cm2 in milk-fed, fermented milk-fed, and
      dehydrated fermented milk-fed guinea pigs, respectively). CONCLUSIONS: The
      intestinal barrier capacity to milk proteins seems to be reinforced by dehydrated
      fermented milk, but milk and fermented milks are equally efficient in inducing
      cow's milk allergy in guinea pigs.

PMID- 9932855
TI  - Cisapride in management of chronic pediatric constipation.
AB  - BACKGROUND: This study was conducted to explore the use of cisapride in the
      treatment of chronic idiopathic constipation in children. METHODS: Seventy-nine
      children were screened. Seventy-three of them met the selection criteria that
      included clinical, laboratory, radiologic, and histopathologic investigations.
      These patients entered a week-long phase I of disimpaction using lactulose. Four
      of them were noncompliant and thus were excluded from the next phase. In phase II
      sixty-nine patients were assigned to two treatment groups: 0.3 mg/kg cisapride
      four times a day versus matching placebo for 8 weeks in a double-blind study. The
      two groups that completed phase II were similar in age and duration of symptoms,
      confirmed by statistical analysis. Stool frequency was assessed weekly, beginning
      at the end of the disimpaction phase and continuing for 9 weeks. Total
      gastrointestinal transit time was measured twice, on completion of phase I and 9
      weeks later. Transit time is the time required for a carmine marker taken orally
      after overnight fast to appear in the stool. RESULTS: There was a significant
      difference between stool frequency per week before and after cisapride treatment,
      stool frequency per week at the end of phase II with cisapride versus placebo,
      and total gastrointestinal transit time before and after treatment with cisapride
      (p < 0.05 for all values). No such difference was demonstrated when comparing
      stool frequency per week or total gastrointestinal transit time before and after
      placebo (p > 0.05 for both). CONCLUSIONS: Cisapride may have a role in the
      management of chronic idiopathic constipation in children.

PMID- 9932856
TI  - Clinical quiz. Schistosoma mansoni.

PMID- 9932857
TI  - Congenital microvillus atrophy in a girl with autosomal dominant
      hypochondroplasia.

PMID- 9932858
TI  - Ulcerative colitis after liver transplant and immunosuppression.

PMID- 9932859
TI  - Delayed response to phenobarbital treatment of a Crigler-Najjar type II patient
      with partially inactivating missense mutations in the bilirubin UDP
      glucuronosyltransferase gene.

PMID- 9932860
TI  - Thalidomide for the treatment of oral aphthous ulcers in Crohn's disease.

PMID- 9932861
TI  - Biliary diversion by use of the appendix (cholecystoappendicostomy) in
      progressive familial intrahepatic cholestasis.

PMID- 9932862
TI  - Spontaneous pneumoperitoneum in a healthy adolescent.

PMID- 9932864
TI  - Vitiligo and Crohn's disease in children.

PMID- 9932863
TI  - Extensive hyperplastic and ulcerative mucosal enteritis in a child requiring
      total enterectomy.

PMID- 9932865
TI  - Serious complications after incomplete removal of percutaneous endoscopic
      gastrostomy catheter.

PMID- 9932866
TI  - On/off antigenic variation in Helicobacter pylori: a clue to understanding immune
      evasion in the host.

PMID- 9932867
TI  - Plasma-induced changes in the physiology of mammalian retinal glial cells: role
      of glutamate.
AB  - Plasma can leak into the nervous system when the vascular endothelial barrier is
      compromised. Although this occurs commonly, little is known about the effects of
      plasma on the function of cells in the central nervous system. In this study, we
      focused on the responses of glial cells, which, because they ensheathe the blood
      vessels, are the first cells exposed to leaking plasma. We used the perforated
      patch configuration of the patch-clamp technique to assess the effects of plasma
      on freshly dissociated bovine and human Muller cells, the principal glia of the
      retina. To monitor the function of Muller cells in situ, we recorded
      electroretinograms from isolated retinas. We found that plasma activates an
      electrogenic glutamate transporter and inhibits inward-rectifying K+ channels, as
      well as a transient outward current. Glutamate, a normal constituent of the
      blood, mimicked these effects. Unlike our recent findings with serum, which
      contains molecules generated by the clotting process, plasma neither activated a
      nonspecific cation conductance nor inhibited the slow P(III) component of the
      electroretinogram, which is generated by Muller cells responding to light-evoked
      changes in the extracellular potassium concentration ([K+]o). Taken together, our
      observations indicate that a leakage of serum into the retina compromises the
      regulation of [K+]o by Muller cells; however, when plasma enters the retina at
      sites of a breakdown in the blood-retinal barrier, these glia can maintain K+
      homeostasis while reducing the potentially neurotoxic levels of glutamate.

PMID- 9932868
TI  - Demyelination and remyelination of the caudal cerebellar peduncle of adult rats
      following stereotaxic injections of lysolecithin, ethidium bromide, and
      complement/anti-galactocerebroside: a comparative study.
AB  - Experimentally induced demyelination due to the direct injection of gliotoxic
      agents has provided powerful models for studying the biology of remyelination.
      For the most part, these models have involved injection into white matter tracts
      of the spinal cord. However, the spinal cord has a number of limitations, such as
      the size of lesions that it is possible to make and its unsuitability for long
      term direct cannulation for the delivery of putative remyelination-enhancing
      agents. In this study, we describe the natural history of three new models of
      demyelination/remyelination based on the stereotaxic injection of three
      gliotoxins: lysolecithin, ethidium bromide, and a combination of anti
      galactocerebroside antibody and complement (GalC-ab/comp) into the caudal
      cerebellar peduncle of adult rats. All three agents produced large areas of
      demyelination with minimal axonal damage, which undergo extensive remyelination.
      Ethidium bromide- and GalC-ab/comp-induced lesions remyelinated more slowly than
      those induced by lysolecithin. The contribution to the remyelination of the
      lesion by Schwann cells reflects the degree of astrocyte damage incurred within
      the demyelinated area and is greatest for ethidium bromide-induced demyelination.
      These new models not only provide further insights into the mechanisms of CNS
      remyelination but also provide a valuable new resource for addressing a series of
      key issues relevant to current efforts to promote CNS remyelination either by the
      enhancement of intrinsic processes or by the transplantation of myelinogenic
      cells.

PMID- 9932869
TI  - Ability of retinal Muller glial cells to protect neurons against excitotoxicity
      in vitro depends upon maturation and neuron-glial interactions.
AB  - Glutamate is the most abundant excitatory amino acid in the central nervous
      system. It has also been described as a potent toxin when present in high
      concentrations because excessive stimulation of its receptors leads to neuronal
      death. Glial influence on neuronal survival has already been shown in the central
      nervous system, but the mechanisms underlying glial neuroprotection are only
      partly known. When cells isolated from newborn rat retina were maintained in
      culture as enriched neuronal populations, 80% of the cells were destroyed by
      application of excitotoxic concentrations of glutamate. Massive neuronal death
      was also observed in newborn retinal cultures containing large numbers of glia,
      or when neurons were seeded onto feeder layers of purified cells prepared from
      immature (postnatal 8 day) rat retina. When newborn retinal neurons were seeded
      onto feeder layers of purified glial cells prepared from adult retinas,
      application of excitotoxic amino acids no longer led to neuronal death.
      Furthermore, neuronal death was not observed in mixed neuron/glial cultures
      prepared from adult retina. However, in all cases (newborn and adult) application
      of kainate led to amacrine cell-specific death. Activity of glutamine synthetase,
      a key glial enzyme involved in glutamate detoxification, was assayed in these
      cultures in the presence or absence of exogenous glutamate. Whereas pure glial
      cultures alone (from young or adult retina) showed low activity that was not
      stimulated by glutamate addition, mixed or co-cultured neurons and adult glia
      exhibited up to threefold higher levels of activity following glutamate
      treatment. These data indicate that two conditions must be satisfied to observe
      glial neuroprotection: maturation of glutamine synthetase expression, and neuron
      glial signalling through glutamate-elicited responses.

PMID- 9932870
TI  - Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes.
AB  - Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains,
      localized in the astrocyte plasma membrane. The regulation of AQP4 is believed to
      be important for the homeostasis of water in the brain, but the AQP4 regulatory
      mechanisms are not yet known. In this study, we investigated the effect of a
      protein kinase C (PKC) activator on the expression of AQP4 mRNA in cultured rat
      astrocytes. Cultured rat astrocytes constitutively expressed AQP4 mRNA. Treatment
      of the cells with 0.1 microM of phorbol ester 12-O-tetradecanoylphorbol 13
      acetate (TPA), an activator of PKC, caused a rapid decrease in AQP4 mRNA. This
      effect was time- and dose-dependent. The TPA-induced decrease in AQP4 mRNA was
      inhibited by a relatively specific PKC inhibitor, 1-(5-isoquinoline sulfonyl)-2
      methylpiperazine (H7) in a dose-dependent manner. Moreover, prolonged treatment
      of the cells with TPA eliminated the subsequent decrease in AQP4 mRNA by TPA.
      These results strongly suggest that the TPA-induced decrease in AQP4 mRNA is
      mediated by PKC activation. To test whether the effect of TPA requires protein
      synthesis, astrocytes were pretreated with cycloheximide, an inhibitor of protein
      synthesis. Pretreatment of the cells with cycloheximide did not inhibit the
      decrease in AQP4 mRNA induced by TPA. To test whether the TPA-induced decrease in
      AQP4 was due to a decrease in the mRNA stability, we examined the effect of
      actinomycin D, an inhibitor of transcription, on TPA-treated cells. The stability
      of AQP4 mRNA was not decreased by the pretreatment of the cells with actinomycin
      D. The results suggest that AQP4 mRNA is inhibited by TPA via PKC activation
      without de novo protein synthesis, and that the inhibition of AQP4 mRNA could be
      at the transcriptional level.

PMID- 9932871
TI  - Cerebellar astrocytes treated by thyroid hormone modulate neuronal proliferation.
AB  - Thyroid hormones are important for neurogenesis and gliogenesis during brain
      development. We have previously demonstrated that triiodothyronine (T3) treatment
      induced proliferation in primary culture astrocytes derived from the cerebellum
      of neonatal rats. Conditioned medium obtained from those T3-treated astrocytes
      (T3CM) mimicked the effect of hormonal treatment on these cells. Because neuron
      glia interaction plays an important role in brain development, we tested the
      ability of such T3-glial CM to influence neuronal physiology. With that aim,
      neurons from 19-day embryonic cerebella were cultivated for 24 h in the presence
      of CM obtained from T3-treated cerebellar astrocytes. Interestingly, the
      cerebellar neuronal population increased by 60-80% in T3CM. Addition of 5 microM
      forskolin enhanced the responsiveness of cerebellar neurons to astrocytes T3CM,
      but it did not interfere with neuronal survival in control medium. Conversely,
      inhibition of adenylate cyclase by its specific inhibitor, SQ22536, reversed the
      T3CM effect on neurons. These data strongly suggest that cAMP signal transduction
      pathways might be implicated in such an event. Analysis of bromodeoxyuridil
      incorporation revealed that the increase in neuron number in T3CM was partially
      due to neuron proliferation, because the proliferation index was three times
      higher in T3CM than in control medium. Neutralizing antibody assays demonstrated
      that T3CM effects on neurons are due, at least in part, to the presence of tumor
      necrosis factor-beta and epidermal growth factor. Thus, we report here a novel
      molecular mechanism of action of thyroid hormone on cerebellar neuronal cells:
      Thyroid hormone induces astrocytes to secrete growth factors that can interfere
      with neuronal proliferation via a paracrine pathway.

PMID- 9932872
TI  - Adult rat olfactory nerve ensheathing cells are effective promoters of adult
      central nervous system neurite outgrowth in coculture.
AB  - A coculture method is described for ensheathing glial cells from adult rat
      olfactory nerve, serving as a substrate for the regrowth of neurites from adult
      rat retinal ganglion cells. Immunocytochemically identified phenotypes present in
      primary cultures of olfactory nerve cells are described, and their ability to
      promote neurite outgrowth is compared with neonatal astrocytes and Schwann cells,
      with other nonglial cells, and with laminin. Ensheathing cell cultures were more
      effective than any other substrate tested and also directed the orientation of
      regrowing neurites. In comparison with cultured Schwann cells, which released
      neurotrophic factors into the culture medium, there was no evidence of a similar
      activity in ensheathing cell cultures. Combinations of ensheathing cell
      conditioned medium and substrates of laminin, merosin, or 3T3 cells also failed
      to show the release of factors enhancing either survival or neurite outgrowth
      from retinal ganglion cells. Evidence is presented for a partial inhibition of
      neurite outgrowth in the presence of calcium channel antagonists or an
      intracellular calcium-chelating reagent. This provides evidence for a
      contribution from an intracellular calcium signaling mechanism, possibly
      implicating ensheathing cell adhesion molecules in promoting neurite outgrowth.

PMID- 9932873
TI  - Metabotropic glutamate receptor agonists reduce glutamate release from cultured
      astrocytes.
AB  - Astrocytes are thought to control extracellular glutamate concentrations ([Glu]o)
      in the brain, thereby protecting neurons from excitotoxic injury. We investigated
      the effects of metabotropic glutamate receptor (mGluR) agonists on glutamate
      transport and [Glu]o in primary hippocampal astrocytic cultures. Acute or chronic
      exposure of astrocytes to the mGluR agonist trans-1-aminocyclopentane-1,3
      dicarboxylic acid (trans-ACPD) or its active isomer 1S,3R-ACPD reduced [Glu]o in
      a time- and dose-dependent manner (44.5 +/- 3.6% reductions of [Glu]o in
      astrocytes from P0-P10 rats and 65.9 +/- 4.1% from rats P20 by 100 microM 1S,3R
      ACPD, EC50 approximately 5 microM). 1S,3R-ACPD effects developed slowly (median
      effective at approximately 60 min) and persisted for several hours after agonist
      removal. ACPD-pretreated astrocytes established lower steady-state [Glu]o levels.
      ACPD effects persisted in the presence of the glutamate uptake inhibitors D,L
      threo-beta-hydroxyaspartate (THA) and L-trans-pyrrolidine-2,4-dicarboxylate (PDC)
      but were impaired by disruption of the transmembrane Na+, K+, or H+ gradients. In
      addition, 1S,3R-ACPD had no effects on intracellular glutamate content and did
      not directly block glutamate transport. Furthermore, ACPD effects could be
      mimicked by glutamate per se and several other compounds presumed to be mGluR
      agonists, although (S)-3,5-dihydroxyphenylglycine (DHPG), (2S,2R,3R)-2-(2,3
      dicarboxycyclopropyl)glycine (DCG-IV), and L-(+)-2-amino-4-phosphonobutyric acid
      (L-AP4) were without effect. These data suggest that glutamate and certain mGluR
      agonists may regulate [Glu]o by modulating the transmembrane equilibrium of
      glutamate transport, especially by attenuating glutamate release.

PMID- 9932874
TI  - Astrocytic glutamate uptake and prion protein expression.
AB  - Factors influencing glutamate uptake by astrocytes may indirectly influence
      neuronal survival. Elevated extracellular glutamate may be excitotoxic or may
      exacerbate neurodegeneration in various neurological diseases. By using a cell
      culture model, we have investigated the influence of astrocytic prion protein
      (PrPc) expression on glutamate uptake. Type 1 astrocytes expressing PrPc have a
      higher rate of Na+-dependent glutamate uptake than PrPc-deficient type 1
      astrocytes. This difference is exacerbated when serum free media is used to
      culture the astrocytes. Further analysis suggested that a decrease in substrate
      affinity is responsible for the sensitivity of PrP-deficient astrocytic glutamate
      uptake to culture conditions. PrPc has been shown to bind copper. Greater
      sensitivity of cells to copper concentrations may be responsible for the
      decreased substrate affinity observed. PrPc-deficient cerebellar cells are more
      sensitive to glutamate toxicity in the presence of copper. These results show
      that glutamate uptake from astrocytes is dependent on PrPc expression which in
      turn may be related to copper metabolism.

PMID- 9932875
TI  - Adenovirus-mediated suicide gene therapy in an in vitro model of reactive
      gliosis.
AB  - Adenovirus-mediated herpes simplex thymidine kinase/ganciclovir (HSV-tk/GCV)
      system has been demonstrated to be efficient for the treatment of experimental
      brain tumors. However, no study has been directed to the elimination of
      proliferating cellular populations in other pathological conditions. In this
      study we used this suicide gene approach in a primary culture of astrocytes, as a
      model of reactive gliosis, in order to evaluate its efficiency as a therapeutic
      strategy for post-traumatic astrogliosis in vivo. First, we evaluated the peak of
      astrocytic proliferation to characterize our model. Second, the efficiency of
      adenovirus-mediated lacZ gene transfer is shown to be dependent on vector
      multiplicity of infection (MOI). As expected, the cells transfected with the HSV
      tk gene showed an increase in sensibility to GCV compared with cells transfected
      with lacZ gene. Finally, an unexpected interaction between the adenoviral vector
      and bromodeoxyuridine (BrdU) or [3H]-Thymidine ([3H]-Thy) was evidenced in
      transfected cultures, whose interpretation is discussed. The present study
      demonstrates that a recombinant adenoviral vector carrying the tk gene confers to
      in vitro cultured astrocytes a cytotoxic sensibility to GCV, and that this system
      constitutes a potentially efficient tool to eliminate the hyperplasia of
      astrocytes following injury to the central nervous system in vivo.

PMID- 9932876
TI  - Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid
      microglia of the developing rat central nervous system.
AB  - Because of morphological similarities between ameboid microglia in the developing
      central nervous system (CNS), brain macrophages in the injured CNS, and cultured
      microglia in vitro, it is thought that these cell types are functionally
      equivalent. To investigate the validity of this assumption, we have compared mRNA
      levels of interleukin-1alpha and -1beta (IL-1alpha and IL-1beta), tumor necrosis
      factor-alpha and -beta (TNF-alpha and TNF-beta), transforming growth factor-beta1
      (TGF-beta1), and macrophage colony-stimulating factor (M-CSF) in the postnatal
      day 4 (P4) supraventricular corpus callosum (SVCC) with those in unstimulated
      cultured microglia. Control tissues included spleen, cortex, hippocampus, and
      cerebellum. Our analyses have shown that while IL-1alpha, IL-1beta, TNF-alpha,
      TNF-beta, and TGF-beta1 transcripts are abundantly expressed by cultured
      microglia, they are very low to virtually undetectable in the SVCC. These data
      strongly suggest that ameboid microglia, which are concentrated in the SVCC, are
      unlikely to be a significant source of these cytokines. Our study, which shows
      clear differences in the functional status of cultured microglia vs. ameboid
      microglia in vivo, stresses the importance of using caution when interpreting in
      vitro findings in terms of the in vivo functions of microglia.

PMID- 9932877
TI  - Gene therapy for cerebrovascular disease.
AB  - OBJECTIVE: To review the principles of and the experimental and clinical results
      of gene therapy for cerebrovascular disease. METHODS: Literature review. RESULTS:
      Vectors for gene transfer into the brain or into the cerebral vasculature include
      naked plasmid deoxyribonucleic acid, cationic liposomes, and viruses such as
      adenovirus, retrovirus, adeno-associated virus, and herpes simplex virus.
      Experiments using these vectors showed that intra- or perivascular application to
      systemic arteries can lead to transfection and expression of a foreign transgene
      in the adventitia and the endothelium. Intrathecal administration can lead to
      transfection and foreign transgene expression in leptomeningeal cells as well as
      in fibroblasts of blood vessel adventitia. Biological effects demonstrated thus
      far include increased nitric oxide production by transfection of cerebral
      arterial adventitia with adenovirus expressing nitric oxide synthase.
      Adenoviruses carrying foreign genes have been used to decrease neuronal damage in
      cerebral ischemia and to decrease blood pressure in spontaneously hypertensive
      rats. Vectors and therapeutic applications for gene therapy are evolving rapidly.
      CONCLUSION: Gene therapy for cerebrovascular disease is likely to have clinical
      application in the near future and will have a major impact on neurosurgery.
      Neurosurgeons will need to be aware of the literature in this area.

PMID- 9932878
TI  - Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long
      term results.
AB  - OBJECTIVE: Prolactinomas are frequently treated primarily with dopamine agonists;
      however, these agents have disadvantages and require life-long therapy. We
      therefore reassessed transsphenoidal microsurgery as an alternative therapy.
      METHODS: We reviewed the data for 121 female patients treated surgically for
      prolactinomas between 1976 and 1979 (Group 1) and 98 patients treated between
      1988 and 1992 (Group 2). RESULTS: Of 219 women, 92% with preoperative prolactin
      (PRL) values of < or = 100 ng/ml and 91% with intrasellar microadenomas
      experienced initial remission; 80 to 88% of patients with intrasellar
      macroadenomas or macroadenomas showing moderate suprasellar extension or focal
      sphenoid sinus invasion experienced remission. Women with PRL values of > 200
      ng/ml and those with larger and more invasive adenomas experienced poorer
      outcomes (37-41% remission). Lower preoperative PRL values and adenoma stage were
      the best predictors of initial surgical outcomes. At the most recent evaluations,
      89% of women who experienced initial remission continued to experience clinical
      remission; 85% exhibited normal PRL values, and 5% demonstrated mild,
      asymptomatic, recurrent hyperprolactinemia (PRL values of < 34 ng/ml). In Group
      1, 84% of patients continued to experience remission (82% with normal PRL values)
      after a median follow-up period of 15.6 years. In Group 2, 97% of patients
      continued to experience remission (88% with normal PRL values) after a median
      follow-up period of 3.2 years. Lower postoperative PRL values were the best
      predictors of long-term remission. CONCLUSION: Transsphenoidal microsurgery is an
      effective alternative to long-term medical therapy for selected patients with
      prolactinomas. Successful outcomes and long-term remission were achieved in
      patients with microadenomas and noninvasive macroadenomas.

PMID- 9932879
TI  - Results of microsurgical treatment for intramedullary spinal cord ependymomas:
      analysis of 36 cases.
AB  - OBJECTIVE: Although intramedullary spinal cord ependymomas are amenable to
      surgical total resection, some ependymomas have been associated with severe
      surgical morbidity. The aim of this study is to determine what factors affect
      surgical morbidity. METHODS: Thirty-six consecutive patients who underwent
      surgical removal of an intramedullary spinal cord ependymoma between September
      1980 and June 1998 were studied retrospectively. This series includes 19 women
      and 17 men between the age of 12 and 67 years (mean age, 41.2 yr). The location
      of the tumors was cervical in 24 cases, cervicothoracic in 3 cases, thoracic in 7
      cases, and conus in 2 cases. At surgery, complete removal was achieved in 34
      patients and subtotal removal was performed in the remaining 2. RESULTS: There
      has been no tumor recurrence in any patient except one who had an anaplastic
      ependymoma after a mean follow-up period of 56 months. The surgery improved
      neurological status in 14 of the 36 patients (39%). However, five patients (14%)
      experienced persistent deteriorations in clinical grade caused by surgery. Four
      of the five patients harbored benign ependymomas in the thoracic cord and
      characteristically demonstrated arachnoid scarring and cord atrophy at surgery,
      indicating that tumors had been present for a long time. CONCLUSION: Surgical
      removal of intramedullary ependymomas is beneficial to patients. However, the
      thoracic cord may be susceptible to surgical manipulations for intramedullary
      ependymomas. In addition, intraoperative findings of arachnoid scarring and cord
      atrophy are ominous for surgical morbidity.

PMID- 9932881
TI  - Spontaneous angiographic obliteration of cerebral arteriovenous malformations.
AB  - OBJECTIVE: The factors associated with spontaneous angiographic obliteration of
      cerebral arteriovenous malformations (AVMs) are not well understood. We present a
      review of the literature and a report of our experience with six cases (four with
      no previous treatment intervention and two postoperative residual malformations)
      that were identified as having occurred during a 20-year period and describe the
      clinical and lesion features associated with this rare phenomenon. We present the
      first detailed histological study of a spontaneously thrombosed AVM specimen,
      including immunohistochemical analysis of angiogenesis factor expression.
      METHODS: A combined experience in the management of approximately 700 AVMs during
      20 years identified six cases of spontaneous angiographic obliteration of
      cerebral AVMs. A literature review revealed another 24 cases with angiographic
      documentation of the initial AVMs and follow-up data showing nonfilling of the
      lesions. Histological analysis of a recently excised lesion included
      immunostaining with monoclonal antibodies to the antigens of Factor VIII, Tie,
      vascular endothelial growth factor, and its receptors, Flt-1 and Flk. RESULTS: A
      single draining vein was a feature in each of our 6 cases and in 12 of 14 (86%)
      cases from the literature. Hemorrhage as the presenting symptom was identified in
      5 of our 6 (83%) cases and in 17 of 24 (71%) of the literature cases. The size of
      the AVM was less than 6 cm in each of our 6 cases and in 22 of 24 (92%) of the
      literature cases. A histological examination of a thrombosed AVM surgical
      specimen revealed persistent patent vascular channels within the lesion.
      Immunohistochemical analysis with angiogenesis and endothelia-specific factors
      showed expression of these factors within the lumen of the thrombosed nidus
      vessels. CONCLUSION: We propose that the occlusion of a single draining vein may
      lead to total venous outflow obstruction and lesion thrombosis. Hemorrhagic
      presentation and small nidus may also predispose to this phenomenon.
      Immunohistochemical analysis of a thrombosed AVM revealed possible ongoing
      angiogenic changes within the AVM vessels 1 month after angiographically
      documented thrombosis. It is possible that neovascularization within a thrombosed
      AVM may lead to lesion recanalization; however, this phenomenon seems to be
      clinically exceedingly rare.

PMID- 9932880
TI  - Intra-arterial Cereport (RMP-7) and carboplatin: a dose escalation study for
      recurrent malignant gliomas.
AB  - OBJECTIVE: Animal and human studies have shown increased delivery of radiolabeled
      compounds across the blood-brain-tumor barrier using intra-arterial (IA) Cereport
      (RMP-7; Alkermes Inc., Cambridge, MA) with a radiolabeled tracer. This present
      study assesses the safety, tolerance, and preliminary efficacy of the IA
      administration of carboplatin with Cereport. METHODS: An open-label dose
      escalation study of IA Cereport (10-300 ng/kg) with 100 mg of IA carboplatin was
      conducted in 11 patients with recurrent malignant gliomas and 1 patient treated
      adjuvantly after radiation therapy. Tumor size and laboratory and clinical
      statuses were assessed. RESULTS: Adverse events were mainly neurological in
      nature and corresponded to the anatomic location of the tumor. Karnofsky
      performance scale scores did not decline, overall, for those patients who had
      tumor response. Tumor shrinkage was observed in three of six evaluable patients
      who received a dose of 300 ng/kg with durable responses of 60, 64, and 106+
      weeks. CONCLUSION: Previous studies have demonstrated increased permeability in
      human gliomas using IA Cereport. This study demonstrates durable imaging
      responses using 100 mg of IA carboplatin in combination with Cereport. The drug
      combination in this patient population seems to be safe and acceptable, providing
      a novel means of antitumor dose intensification.

PMID- 9932882
TI  - A prospective study of long-term intrathecal morphine in the management of
      chronic nonmalignant pain.
AB  - OBJECTIVE: To examine in a prospective manner the long-term safety and efficacy
      of chronic intrathecal morphine in patients with severe, nonmalignant pain
      refractory to less invasive modalities. METHODS: Forty patients with severe,
      chronic nonmalignant pain poorly managed by systemic medications were identified
      as candidates for intraspinal trial of morphine. Thirty participants reported
      successful pain relief during trial and were implanted with an intraspinal
      delivery system. Standardized measures of pain and functional status were
      assessed before treatment was begun and at defined intervals during the
      subsequent 24 months. Intrathecal opioid use and pharmacological and device
      related complications were also monitored. RESULTS: The participants had a mean
      age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three
      percent of the study participants were women. Pain type was characterized as
      mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic
      (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive
      (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with
      failed back surgery syndrome. Significant improvement over baseline levels of
      visual analog scale pain was measured at each follow-up examination after
      implant. Overall, 50% (11 of 22 patients) of the population reported at least a
      25% reduction in visual analog scale pain after 24 months of treatment. In
      addition, the McGill Pain Questionnaire, visual analog scale measures of
      functional improvement and pain coping, and several subscales of the Chronic
      Illness Problem Inventory showed improvement throughout the follow-up period.
      Pharmacological side effects were managed medically by morphine dose reduction,
      addition of bupivacaine, or replacement of morphine with hydromorphone. Device
      related complications requiring repeat operations were experienced by 20% of the
      patients. CONCLUSION: Continuous intrathecal morphine can be a safe, effective
      therapy for the management of severe, nonmalignant pain among a carefully
      selected patient population and can result in long-term improvement in several
      areas of daily function.

PMID- 9932883
TI  - Magnetic resonance imaging-based stereotactic localization of the globus pallidus
      and subthalamic nucleus.
AB  - OBJECTIVE: To optimize the accuracy of initial stereotactic targeting for
      movement disorders surgery, we performed stereotactic localization of the
      internal segment of the globus pallidus (GPi) and subthalamic nucleus (STN) using
      magnetic resonance imaging protocols in which the borders of these nuclei were
      directly visualized. METHODS: Fifty-one consecutive cases using the pallidal
      target and six using the subthalamic target were studied. Localization of these
      nuclei was performed using the Leksell stereotactic head frame and inversion
      recovery sequences (GPi) or T2-weighted spin echo sequences (STN). Targeting
      accuracy and individual variation in the spatial coordinates of these structures
      were independently measured by identification of nuclear boundaries during
      multiple microelectrode penetrations. RESULTS: The lateral and vertical
      coordinates of an atlas-defined point in the GPi, with respect to the line
      between the anterior and posterior commissures, was highly variable. Initial
      targeting the GPi based on direct visualization of the target boundaries
      (external medullary lamina and optic tract) resulted in greater precision than
      would be expected using fixed anterior and posterior commissure-based
      coordinates. Initial targeting the STN using magnetic resonance imaging was
      sufficiently precise to place the initial microelectrode penetration within STN
      in all six cases. CONCLUSION: Magnetic resonance imaging-based initial
      stereotactic targeting of the GPi, based on direct visualization of the target
      boundaries, is useful to improve target accuracy over that of purely indirect
      anterior and posterior commissure-based targeting methods. Initial targeting of
      the STN was reliably accomplished by direct visualization. However, there remains
      sufficient variability that the final target location in both GPi and STN
      required electrophysiological mapping in all cases.

PMID- 9932884
TI  - Microelectrode recording during posteroventral pallidotomy: impact on target
      selection and complications.
AB  - OBJECTIVE: To assess the practical usefulness of single-cell microelectrode
      recording (MER) when performing posteroventral pallidotomy. METHODS: A
      retrospective comparison of the initial, magnetic resonance imaging-derived
      coordinates of the pallidotomy target to the final, MER-refined lesion
      coordinates in 132 consecutive pallidotomies was conducted. The time required to
      perform the procedure and the surgical complications are reported. RESULTS: MER
      led to targeting changes in 98% of the cases. In 12%, the MER-refined target was
      more than 4 mm from the original, image-guided site, which is a targeting error
      that could adversely affect outcome. Although all components of targeting were
      affected by MER, laterality and depth were impacted most. The ventral border of
      the globus pallidus pars interna was located within 1 mm of the magnetic
      resonance imaging-selected target in only 40% of the cases. On average, only 2.2
      MER trajectories were required to perform pallidotomy. During the last 3 years of
      our study, 85% of the procedures were performed with one or two trajectories. The
      mean operating time of the operations performed during the last 3 years was 2
      hours and 12 minutes. The incidence of intracerebral hemorrhage in our series
      (1.5%) was no higher than that reported for other large series of stereotactic
      procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides
      important targeting information for performing pallidotomy. In particular, the
      micrometric delineation of the ventral border of the globus pallidus pars interna
      permits safe lesioning of the posteroventral region of the globus pallidus pars
      interna with little risk of visual field deficit. These data can be obtained
      efficiently and without increased surgical risk.

PMID- 9932885
TI  - Occipitocervical fixation using hooks and screws for upper cervical instability.
AB  - OBJECTIVES: Occipitocervical fixation is used for the treatment of nontraumatic
      upper cervical instabilities. To date, plates have been fixed with screws or
      wires. However, these devices are not indicated in the treatment of patients with
      severe osteoporosis or in instances of significant thinning of the occipital
      bone. We performed a clinical trial of a new type of fixation that uses cervical
      interlaminar hooks and occipital claws with hooks or with screws (CCD type;
      Sofamor-Danek, Roissy, France) for the treatment of nontraumatic upper cervical
      instabilities. METHODS: Five women and one man ranging in age from 28 to 72 years
      (average age, 54 yr) were thus treated. The CCD type material had two rod plates
      and hooks allowing the proper placement of interlaminar and occipital claws. The
      occipital plate can also be directly screwed to the bone. Occipital hooks were
      used in four patients. The other two patients, who had occipitocervical
      congenital abnormalities that required an occipitocervical opening and an
      additional dural enlargement, underwent occipital screw fixation because of the
      previous opening of the foramen magnum. A cancellous iliac autograft allowed the
      usual fusion. RESULTS: No postoperative complications were observed, and all
      patients experienced significant improvement of their neck pain. Four patients
      had neurological symptoms. The condition of two patients improved, and the
      condition of the other two stabilized. CONCLUSION: This report confirms the
      interest of the CCD method to correct all types of upper cervical instabilities,
      even in cases of unusual thinning of the occipital bone or in osteoporotic
      states.

PMID- 9932886
TI  - Evaluation of application techniques of fibrin sealant to prevent cerebrospinal
      fluid leakage: a new device for the application of aerosolized fibrin glue.
AB  - OBJECTIVE: This report evaluates the sealing effects of fibrin sealant applied on
      the dura mater using different techniques. METHODS: Three application methods
      were studied: a sequential layer method, a simultaneous method using a cannula,
      and a spray method using a newly developed spray device. The sealing effects of
      these methods were compared using in vitro histological analysis and a pressure
      resistance test. The clinical efficacy of the fibrin sealant to prevent water
      leakage through the dura mater was retrospectively analyzed in a total of 509
      patients. The process of absorption of a clinically applied fibrin clot in vivo
      was examined using surgical specimens. RESULTS: The fibrin plate made using the
      spray method withstood a hydrostatic pressure greater than 200 cm H2O. A scanning
      electron microscopic study of the fibrin clots showed that the sequential and
      simultaneous methods produced a fibrin fiber network; in contrast, our spray
      method formed a dense fibrin tissue in which the fibrin molecules fused together
      forming stratified laminae. Of the 295 supratentorial craniotomies during which
      spraying was used, postsurgical cerebrospinal fluid leakage occurred in 9 cases
      (3.1%), whereas of the 214 craniotomies during which spraying was not used,
      cerebrospinal fluid leakage occurred in 19 cases (8.9%). Histological
      examinations of 10 surgical specimens obtained during second craniotomies
      revealed that the spray-made fibrin clots had been gradually replaced by mature
      granulation composed of collagenous connective tissue. CONCLUSION: The optimal
      technique for applying fibrin sealant is the spray method that aerosolizes fibrin
      glue and produces a tough fibrin plate.

PMID- 9932887
TI  - Transcollicular approach to intrinsic tectal lesions.
AB  - OBJECTIVE: We used a paramedian, infratentorial-supracerebellar, transcollicular
      approach to resect 11 intrinsic tectal lesions, including 8 tumors and 3
      hematomas, in 11 patients. The route of access to the lesions was designed to
      minimize the anatomic and functional damage to the surrounding structures.
      METHODS: Access was through one superior colliculus in each of seven patients,
      through one inferior colliculus in each of two patients, and through the superior
      and inferior colliculi of one side in each of two patients. RESULTS: Of the eight
      tumors, three were totally resected, four were nearly totally resected, and one
      was partially resected. The preoperative ocular symptoms did not change in six of
      these eight patients and worsened in two, and the neurological deficits, except
      ocular symptoms, improved in two. All three hematomas were completely removed,
      along with abnormal blood vessels in the wall of the hematoma cavity; all three
      of these patients experienced neurological improvement. CONCLUSION: We conclude
      that the paramedian, infratentorial-supracerebellar, transcollicular approach
      permits safe removal of intrinsic tectal lesions. Resection of the superior or
      inferior colliculus or both on one side seems to be neurologically well
      tolerated.

PMID- 9932888
TI  - Fiberoptic delivery of laser energy to remove occlusions from ventricular shunts:
      technical report.
AB  - OBJECTIVES: Shunts frequently require surgical replacement because occlusions
      block the ventricular tubing. We have examined the hypothesis that a surgical
      laser coupled to an optical fiber can deliver sufficient energy to disrupt the
      occlusion in situ and thus afford a less invasive method of repair. METHODS:
      Choroid plexus tissue found in shunts explanted from patients, model tissues such
      as polyacrylamide gel, and animal tissues inserted into shunts were examined.
      Occlusions were fragmented by pulsed laser energy of 2.09-microm wavelength and
      300-microsecond duration delivered via a flexible optical fiber several meters in
      length. The methods and conditions were similar to those likely to be used for
      preclinical in vivo studies. RESULTS: Short-lived vapor bubbles generated at the
      fiber tip disrupted occlusions within the shunt and expelled tissue blocking the
      inflow holes. Energy requirements to disrupt and remove occlusions in vitro were
      determined. Laser pulse energies and exposure thresholds that cause intentional
      damage to shunts also were determined. CONCLUSION: Laser energies needed to
      disrupt occlusions were below the energy needed to damage the shunt components.
      Our results show that a strategy using surgical lasers and optical fibers is
      feasible and suggest that the procedure could be used to repair blocked shunts
      without requiring surgical replacement.

PMID- 9932889
TI  - Enhanced delivery of boronophenylalanine for neutron capture therapy of brain
      tumors using the bradykinin analog Cereport (Receptor-Mediated Permeabilizer-7).
AB  - OBJECTIVE: Using the well-characterized F98 rat glioma model, the purpose of the
      present study was to determine whether the delivery of boronophenylalanine (BPA)
      could be enhanced by prior administration of the bradykinin analog Cereport
      (Alkermes, Inc., Cambridge, MA) (previously known as Receptor-Mediated
      Permeabilizer-7), which produces a transient, pharmacologically mediated opening
      of the blood-brain barrier. METHODS: Two series of experiments were performed in
      F98 glioma-bearing rats that had received either intracarotid (i.c.) or
      intravenous infusions of Cereport (at doses ranging from 1.5 to 7.5 microg/kg of
      body weight), followed by i.c. (or intravenous) injection of BPA (300 mg/kg of
      body weight). Animals were killed 0.5, 2.5, or 4 hours later, samples of blood,
      skin, muscle, and eye were obtained, brains were removed, and tumors were excised
      for boron determination by direct current plasma-atomic emission spectroscopy.
      RESULTS: Averaged over all time points, i.c. infusion of Cereport significantly
      enhanced tumor boron uptake (P = 0.0001), compared with the excipient (saline)
      control values. Tumor boron values were equivalent at 0.5 (36.0 microg/g) and 2.5
      hours (38.5 microg/g) after i.c. administration of Cereport and BPA and then
      decreased by 33% (to 25.7 microg/g) at 4 hours. These tumor boron uptake values
      were significantly different (alpha = 0.05), compared with values measured at the
      corresponding times after i.c. administration of BPA without Cereport (22.6,
      21.8, and 15.3 microg/g, respectively). Although no time-related effects were
      observed, i.c. administration of Cereport followed by intravenous administration
      of BPA also significantly enhanced (alpha = 0.05) tumor boron uptake at 0.5, 2.5,
      and 4 hours (27.4, 30.3, and 28.0 microg/g, respectively), compared with values
      obtained without Cereport (11.3, 13.4, and 15.2 microg/g, respectively). Boron
      levels in normal brain tissue from tumor-bearing and non-tumor-bearing cerebral
      hemispheres and in blood were not significantly different from those measured in
      saline-treated control animals. CONCLUSION: This study established that i.c.
      infusion of Cereport significantly increased delivery of BPA to F98 rat gliomas,
      and this could enhance the efficacy of boron neutron capture therapy of this
      tumor.

PMID- 9932890
TI  - Connexins are expressed in primary brain tumors and enhance the bystander effect
      in gene therapy.
AB  - OBJECTIVE: Experimental brain tumor gene therapy with the herpes simplex virus
      thymidine kinase (HSV-tk) gene has demonstrated that not only HSV-tk transduced
      but surrounding non-HSV-tk transduced cells are killed when given ganciclovir.
      This so-called bystander effect has recently been shown to be dependent on
      connexin-mediated intercellular communication. To assess potential susceptibility
      to the bystander effect, we examined levels of connexin-26 and connexin-43
      expression in a series of primary brain tumors. Connexin-26 expression has not
      previously been studied in primary brain tumors and connexin-43 expression has
      not been studied in nonastrocytic primary brain tumors. We also attempted to
      enhance the bystander effect in vitro by overexpressing connexin in tumor cells
      with high basal levels of connexin expression. METHODS: Western blot analysis and
      immunohistochemistry were used to determine levels of connexin-26 and connexin-43
      expression in a series of primary brain tumors. Wild-type 9L gliosarcoma cells
      were transfected in vitro with the connexin-43 gene and the HSV-tk gene or the
      HSV-tk gene alone. The bystander effect of each transfectant was then assessed
      and compared. RESULTS: Most of the primary brain tumors tested, including low
      grade astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas,
      gangliogliomas, meningiomas, and medulloblastomas, showed connexin-26 and
      connexin-43 expression. Bystander experiments revealed a significant enhancement
      of the bystander effect in the gliosarcoma cells transfected with connexin-43 and
      HSV-tk, as compared with gliosarcoma cells transfected with HSV-tk alone.
      CONCLUSION: Most primary brain tumors express connexin-26 and connexin-43. This
      suggests that most primary brain tumors may be susceptible to the bystander
      effect of HSV-tk gene therapy. The bystander effect can be enhanced in vitro by
      overexpression of connexin-43 in a cell line with a high basal level of connexin
      43 expression.

PMID- 9932891
TI  - Effect of ebselen on contractile responses in perfused rabbit basilar artery.
AB  - OBJECTIVE: To evaluate the possible role of the antioxidant ebselen in the
      treatment of cerebral vasospasm, we examined the effects of ebselen on the
      vasoactive mechanisms induced by endothelin (ET)-1, oxyhemoglobin, and oxygen
      derived radicals. METHODS: Isolated rabbit basilar arteries with intact
      endothelium were fixed in a perfusion system and perfused intraluminally.
      Contraction of the artery was detected as an increase in perfusion pressure.
      RESULTS: Ebselen, in a certain concentration range (3 x 10(-6) and 10(-5) mol/L),
      significantly reduced the contractile response to ET-1 (10(-10) to 10(-8) mol/L)
      but not the contraction induced by 40 mmol/L potassium. It reduced the
      contraction induced by 10(-4) mol/L 1,2-dioctanoyl-sn-glycerol, a protein kinase
      C activator. Addition of 10(-5) mol/L dithiothreitol, a sulfhydryl-reducing
      agent, partially reversed the inhibitory effects of ebselen on ET-1- and 1,2
      dioctanoyl-sn-glycerol-induced contractions. Ebselen (10(-5) mol/L) as well as a
      combination of catalase (1000 units/mL) and superoxide dismutase (150 units/mL)
      inhibited the potentiating effects of oxyhemoglobin (10(-5) mol/L) on ET-1
      induced contraction. Both ebselen and catalase inhibited the contractile response
      to hydroxyl radical generated by ferrous ion (10(-3) mol/L) plus hydrogen
      peroxide (10(-2) mol/L). Ebselen reduced the response to potassium when a high
      dose (3 x 10(-5) mol/L) was applied and failed to preserve contractility of the
      preparation after exposure to hydroxyl radical. CONCLUSION: Ebselen suppressed ET
      1-induced contraction and synergetic interaction between oxyhemoglobin and ET-1,
      where free radical formation was involved. These effects may result from
      modification of the intracellular regulatory system including protein kinase C,
      as well as from protection against free radicals.

PMID- 9932893
TI  - The enigmatic foramen lacerum.
AB  - OBJECTIVE: The microanatomic details of the foramen lacerum and surrounding
      region are described to clarify the relationship between the internal carotid
      artery and the foramen lacerum. The terminology related to these structures is
      reevaluated. Examples of pathological abnormalities restricted to the foramen
      lacerum region are presented to document the clinical relevance of this region.
      METHODS: Microanatomic dissections were performed in 12 formalin-fixed cadaveric
      specimens. Bony landmarks were examined in 50 dry skulls. Microscopic sections of
      the region were obtained from cadaveric specimens that were formalin-fixed,
      decalcified, and processed for histological examination. RESULTS: The foramen
      lacerum is not a true foramen. No significant structures traverse its
      fibrocartilage. In this region, the bony and fibrous structures surround the
      internal carotid artery to form an incomplete canal, which serves as the rostral
      extension of petrous canal. CONCLUSION: The term foramen lacerum should be
      restricted to that portion of the cranial base at the confluence of the petrous
      portion of the temporal, basioccipital, and basisphenoid bones that in vivo is
      filled with fibrocartilage. The region immediately above the foramen lacerum,
      occupied by the internal carotid artery and traditionally considered the upper
      portion of the foramen lacerum, should be considered, anatomically and
      functionally, to be the rostral extension of the petrous canal. We suggest
      calling this extension the lacerum portion of the carotid canal.

PMID- 9932892
TI  - Intradiscal pressure recordings in the cervical spine.
AB  - OBJECTIVE: Experimental investigations analyzing the biomechanics of the cervical
      spine are less common than similar studies of other regions of the spine. There
      are no reports on cervical intradiscal pressure (PID) measurements in vitro. We
      therefore wanted to establish normal values for PID under physiological
      conditions by simultaneous muscle force simulation. Moreover, the impact of
      ventral cervical fusion should be elucidated, because in clinical studies, it is
      a well-known phenomenon that the adjacent segments often show increased
      degenerative changes. We present a pilot study. METHODS: Seven human cervical
      spine specimens were tested biomechanically in a specially developed spine
      tester. Only pure moments were used for flexion/extension, axial rotation, and
      lateral bending (maximal moment +/- 0.5 Nm). PID was measured simultaneously in
      C3-C4 and C5-C6. The specimens were tested as intact specimens and after
      discectomy and fusion in C4-C5. Both test situations were repeated with
      simulation of muscle forces. RESULTS: We found characteristic load-pressure
      curves for each of the three motion axes. In neutral position, PID correlated
      well with former published data from in vivo measurements. After fusion of C4-C5,
      there was a marked increase of PID in both adjacent segments (e.g., < or = 180%
      for axial rotation). With muscle force simulation, the increase was even higher
      (e.g., < or = 400% for axial rotation). CONCLUSION: For the first time, PID could
      be measured in the cervical spine in an experimental setting. The results
      obtained using normal specimens under physiological conditions confirmed those
      reported in two clinical studies. After cervical fusion, a marked increase in PID
      could be found in both adjacent segments. Presuming that an increase in PID had a
      negative effect on metabolism of the intervertebral disc, our results may help to
      explain why progressive degeneration occurs in these segments.

PMID- 9932894
TI  - Fenestrated oculomotor nerve caused by meningioma around the cavernous sinus: a
      surgical pitfall in tumor removal: case report.
AB  - OBJECTIVE AND IMPORTANCE: The preservation of oculomotor nerves is one of the
      most significant issues regarding the resection of meningiomas around the
      cavernous sinus. CLINICAL PRESENTATION: We report the case of a patient whose
      oculomotor nerve was fenestrated, caused by a large meningioma around the
      cavernous sinus. The nerve function remained intact until surgery. INTERVENTION:
      During surgery, one trunk of the fenestrated nerve behind the tumor was
      sacrificed. The fenestrated shape of the nerve led us to the misjudgment that the
      preserved other trunk located along the upper margin of the tumor was the whole
      nerve. CONCLUSION: Although fenestrated oculomotor nerves may be rare, their
      possibility should be kept in mind during surgery around the cavernous sinus.

PMID- 9932895
TI  - Sacrococcygeal teratoma with an intradural and extramedullary extension in a
      neonate: case report.
AB  - OBJECTIVE AND IMPORTANCE: The intradural extension of a sacrococcygeal teratoma
      is rare and has been reported previously in only two cases. We present a case of
      a sacrococcygeal teratoma with an intradural and extramedullary extension.
      CLINICAL PRESENTATION: The patient was a full-term female infant, born with a
      sacral mass. Ultrasonography, computed tomography, and magnetic resonance imaging
      showed an intraspinal extension. INTERVENTION: The operation confirmed the
      extension of the mass up to the T4 level, and total tumor removal was achieved.
      The pathological examination showed a mature teratoma. CONCLUSION: The
      postoperative course was uneventful, and at the 3-year follow-up examination, the
      patient had experienced normal growth without deficit in the lower limbs but had
      a neurogenic bladder. Magnetic resonance imaging disclosed no tumor recurrence.
      This case represents the third case in the literature of an intradural extension
      of a sacrococcygeal teratoma and the first one with an extramedullary component
      so extensive.

PMID- 9932896
TI  - Aggressive enterogenous cyst with extensive craniospinal spread: case report.
AB  - OBJECTIVE AND IMPORTANCE: Considered benign and malformative in nature,
      enterogenous cysts are predominantly spinal lesions. Although recurrences have
      been reported, especially in the rare intracranial examples, craniospinal
      dissemination has never been described. CLINICAL PRESENTATION: We report a 63
      year-old woman who presented 16 years previously with a histologically typical
      enterogenous cyst of the cerebellum. Fourteen years after its incomplete
      excision, numerous supratentorial, infratentorial, and spinal subarachnoid cysts
      were detected. A histological examination revealed multiple enterogenous cysts
      without evidence of malignancy. Ki-67 (MIB-1) proliferative indices were less
      than 1% in all except one specimen, wherein it was 4%; immunohistochemistry
      demonstrated rare p53 protein overexpression. INTERVENTION: During the last 2
      years, four subtotal resections of spinal enterogenous cysts have been performed
      for progressive paraplegia, pain, paresthesia, and bladder dysfunction.
      Considering the multiple recurrences and progressive neurological deficits,
      craniospinal radiation therapy was given. CONCLUSION: To our knowledge, this is
      the first report of widespread craniospinal dissemination associated with the
      incomplete resection of an enterogenous cyst. Although a rare complication, it
      emphasizes the advantages of early, aggressive surgery.

PMID- 9932897
TI  - Primary spheno-orbital angiosarcoma: case report and review of the literature.
AB  - OBJECTIVE: Angiosarcoma is a rare neoplasm that uncommonly involves the cranium.
      We report the second case in the literature of a primary right spheno-orbital
      malignant angiosarcoma. CLINICAL PRESENTATION: This 43-year-old man experienced a
      3-month history of rapid growing temporal mass. The results of his neurological
      examination were normal. Neuroimaging revealed an intensively enhanced right
      spheno-orbital lesion, with destruction of the greater wing of the sphenoid bone
      and extension into the orbit, the infratemporal fossa, and the temporal fossa
      with infiltration of the dura mater but without parenchymal abnormality.
      INTERVENTION: The tumor was first biopsied and then totally removed, with
      exenteration of the right eye. The histological features were typical of
      angiosarcoma with immunohistochemical evidence of Factor VIII-related antigen
      produced by tumor cells. Neither radiotherapy nor chemotherapy was performed. The
      patient remained well during 16 months of follow-up, without evidence of
      recurrence on magnetic resonance images. CONCLUSION: We emphasize the benefit of
      wide surgical resection without systematic complementary treatment (radiotherapy
      and/or chemotherapy) in a case of primary angiosarcoma of the cranium. The
      literature is reviewed.

PMID- 9932898
TI  - Traumatic epidural hematoma of the cervical spine: magnetic resonance imaging
      diagnosis and spontaneous resolution: case report.
AB  - OBJECTIVE AND IMPORTANCE: Demonstration of interest of medical treatment of
      cervical epidural hematomas. CLINICAL PRESENTATION: A young patient developed
      cervical pain after experiencing cervical trauma. Computed tomography and
      magnetic resonance imaging demonstrated an epidural cervical hematoma. A
      spontaneous resolution of the clinical symptoms and the radiological
      abnormalities was observed. CONCLUSION: Although surgical decompression is
      generally regarded as mandatory in selected patients with incomplete and
      nonprogressing deficits, conservative management may be possible.

PMID- 9932899
TI  - Type A immunoglobulin deficiency presenting as a mixed polymicrobial brain
      abscess: case report.
AB  - OBJECTIVE AND IMPORTANCE: We present a case report of a patient with a left
      frontal brain abscess. Cultures obtained from the abscess at the time of surgery
      were identified as dental flora known to establish a synergistic relationship in
      polymicrobial infections. This type of synergistic relationship makes the
      clearance of an infection more difficult for an intact immune system. A serum
      immunoglobulin (Ig) Type A deficiency was identified postoperatively. This
      immunodeficiency may have contributed to the development of the abscess. CLINICAL
      PRESENTATION: The patient presented with headaches and photophobia. Computed
      tomography of the head performed with intravenously administered contrast
      demonstrated a left frontal brain abscess. INTERVENTION: The patient was operated
      on through a left frontal approach, carefully avoiding the frontal sinus. The
      abscess was aspirated, and the patient was treated with intravenous antibiotics
      for several weeks. Postoperatively, the patient did well. There were no signs of
      enhancement on follow-up computed tomographic scans at 7 and 12 months
      postoperatively. CONCLUSION: Through a comprehensive immunological workup, an IgA
      deficiency was identified postoperatively. Although the deficiency of a single
      type of Ig may be asymptomatic, complications from recurrent or chronic bacterial
      infections may occur. The deficiency of IgA, combined with a synergistic
      polymicrobial infection, contributed to the development of an intracranial
      abscess. A patient presenting with a brain abscess without any predisposing
      medical history should be evaluated for an underlying immune deficiency.

PMID- 9932900
TI  - Combined pretemporal and endovascular approach to the cavernous sinus for the
      treatment of carotid-cavernous dural fistulae: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The endovascular treatment of carotid-cavernous dural
      fistulae is becoming the prominent treatment modality for these lesions. The
      intractability of these lesions and their tendency to recur, especially after
      previous endovascular treatment sessions, exhausts the available routes and tends
      to present a difficulty in accessing the cavernous sinus. To avoid the risks
      associated with a direct surgical approach, an alternative, less invasive route
      to the cavernous sinus using a pretemporal extradural approach is combined with a
      direct endovascular approach. CLINICAL PRESENTATION: A 38-year-old woman
      presented with a history of right visual and ocular symptoms related to a Type D
      cavernous carotid dural fistula, which was fed by internal carotid and external
      carotid branches. The fistula was initially treated with embolization of the
      external carotid arterial supply. After a transient improvement, the patient's
      visual acuity worsened. A follow-up angiogram showed the major supply from the
      intracavernous internal carotid branches and draining through the inferior
      ophthalmic vein. The transvenous route was not accessible. An attempt to
      cannulate the intracavernous branches was not successful. The combined
      pretemporal and endovascular approach was then used. INTERVENTION: The
      pretemporal extradural region of the superior orbital fissure was exposed. Using
      microsurgical techniques and Doppler flow guidance, the anterior cavernous sinus
      was cannulated through the orbital venous drainage channels. Using intraoperative
      angiography, thrombogenic coils were deployed at the level of the fistula.
      Intraoperative angiography confirmed complete obliteration of the fistula.
      CONCLUSION: The combined pretemporal (extradural) and endovascular approach to
      the cavernous sinus is a less invasive alternative for the treatment of
      intractable carotid-cavernous dural fistulae.

PMID- 9932901
TI  - Cervical intrathecal catheter placement for cerebrospinal fluid drainage:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The purpose of this report is to describe the placement
      and use of a cervical subarachnoid catheter for cerebrospinal fluid diversion.
      This technique provides an important alternative drainage system for patients
      whose clinical situations preclude lumbar spinal fluid diversion. CLINICAL
      PRESENTATION: Two patients were involved in accidents that resulted in traumatic
      dural tears. Both patients required thoracolumbar spinal reconstruction with
      instrumentation. Cerebrospinal fistulae developed, which were refractory to
      surgical reexploration. TECHNIQUE: A commercially available catheter was
      successfully placed in the cervical subarachnoid space under fluoroscopic
      guidance using a C1-C2 approach in both patients. Spinal fluid drainage was
      maintained for 5 days via this route, and this proved effective in resolving the
      cerebrospinal fluid fistula. No complications were observed with the placement or
      maintenance of the catheter. CONCLUSION: Cervical spinal fluid drainage is a
      feasible alternative for patients in whom lumbar access cannot be obtained or is
      contraindicated.

PMID- 9932902
TI  - Using hydroxylapatite ceramic buttons covered with periosteum to prevent
      cerebrospinal fluid leakage: technical note.
AB  - BACKGROUND: Many attempts have been made to prevent cerebrospinal fluid (CSF)
      leakage, but the procedures proposed to date are troublesome and not promising.
      We describe a method of completely preventing CSF leakage using hydroxylapatite
      ceramics. METHODS: Exposed frontal sinus, mastoid air cells, and frontal base
      defects caused by fracture are covered with periosteum or fascia and plugged with
      a trimmed hydroxylapatite ceramic button. RESULTS: There was no CSF leakage,
      postoperative meningitis, or other complication related to the technique in a
      consecutive series of 25 patients treated using this procedure. CONCLUSION: The
      use of this easy and quick technique may prevent CSF leakage completely.

PMID- 9932903
TI  - Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience
      with proton beam therapy in 98 cases at the Harvard Cyclotron.

PMID- 9932904
TI  - John Farquhar Fulton.

PMID- 9932905
TI  - Venous air embolism in sitting and supine patients undergoing vestibular
      schwannoma resection.

PMID- 9932906
TI  - Lymphocytic and granulomatous hypophysitis: experience with nine cases.

PMID- 9932907
TI  - Surgical removal of a choroid plexus adenoma using the argon beam coagulator:
      technical case report.

PMID- 9932908
TI  - Radical excision of intramedullary cavernous angiomas.

PMID- 9932909
TI  - The role of peritoneal immunity and the tumour-bearing state on the development
      of wound and peritoneal metastases after laparoscopy.

PMID- 9932910
TI  - Flexing up for screening by flexible sigmoidoscopy.

PMID- 9932911
TI  - Prevention of venous thrombo-embolism. National Working Party on the Prevention
      and Management of Venous Thrombo-embolism and Chronic Venous Insufficiency.

PMID- 9932912
TI  - Hereditary non-polyposis colorectal cancer syndrome.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) syndrome may account for up to
      4% of the total colorectal cancer burden in our community. It is assuming an
      increasingly important role, both as a clinical management issue and as a model
      for the application of laboratory and clinical genetic services in cancer
      detection and prevention. Recent developments in the understanding of the
      molecular biology of the condition have underpinned recommendations for
      consideration of genetic testing for DNA mismatch repair gene mutation,
      recommendations that may have far-reaching implications in terms of the numbers
      of patients offered genetic testing and for associated costs (both financial and
      psychological). The aim of this review is to highlight the clinical, pathologic
      and molecular biologic features of HNPCC that underlie the clinical management of
      affected index patients and their at-risk family members.

PMID- 9932913
TI  - The role of peritoneal immunity and the tumour-bearing state on the development
      of wound and peritoneal metastases after laparoscopy.
AB  - BACKGROUND: The effect of the tumour-bearing state and alterations in peritoneal
      immune function on the incidence of port-site and peritoneal metastases was
      investigated after laparoscopy with and without CO2 pneumoperitoneum. METHODS: A
      suspension of viable adenocarcinoma cells was introduced into the left upper
      quadrant of the peritoneal cavity of syngeneic tumour-bearing rats at laparotomy,
      laparoscopy with CO2, and gasless laparoscopy. Control rats did not have pre
      existing tumours. A group of non-tumour-bearing rats were also injected
      intraperitoneally with endotoxin 4 h before intraperitoneal tumour cell
      injection. Six days later the peritoneal cavity and surgical wounds were examined
      for macroscopic evidence of implanted tumour. Peritoneal macrophages were
      obtained from tumour-bearing rats subjected to different laparoscopic procedures
      and the activation state measured following exposure to lipopolysaccharide in
      vitro. RESULTS: In the control rats, tumour implantation in the surgical wounds
      and peritoneum was significantly greater in the rats that had undergone
      laparoscopy with CO2. The presence of a pre-existing tumour was associated with
      increased tumour spread in all treatment groups and at most sites. Injection of
      endotoxin also resulted in increased tumour spread. Peritoneal macrophages from
      control and tumour-bearing rats who underwent laparoscopy with CO2 produced
      significantly less TNF-alpha in vitro, compared to gasless laparoscopy or
      laparotomy. CONCLUSIONS: Carbon dioxide insufflation enhances tumour spread and
      implantation. The underlying immune or metabolic status of the host, as
      influenced by the tumour-bearing state or modification of the peritoneal
      environment, also has a marked independent effect on tumour spread and
      implantation. The immune and metabolic status of the peritoneum including the
      extent of macrophage activation is implicated in this effect.

PMID- 9932914
TI  - Difficult or incomplete flexible sigmoidoscopy: implications for a screening
      programme.
AB  - BACKGROUND: Pilot studies are currently underway to investigate the use of
      flexible sigmoidoscopy as a screening tool for colorectal cancer. Estimates of
      the sensitivity of this investigation in detecting adenomas and carcinomas
      frequently assume a complete examination to 60 cm in all cases. This study seeks
      to determine the depth of insertion of flexible sigmoidoscopy in asymptomatic
      volunteers, and to examine the causes and implications of an incomplete
      examination. METHODS: A prospective study of flexible sigmoidoscopy in
      asymptomatic volunteers was conducted. The maximum depth of insertion was
      measured in all cases, and a database compiled of patient characteristics,
      discomfort and endoscopic difficulty. RESULTS: Independent risk factors for
      reduced depth of insertion were female sex, previous abdominal surgery in
      females, high expectation of pain in females and poor bowel preparation. The
      procedure was considered difficult in 33% of cases. CONCLUSIONS: Estimates of the
      efficacy of flexible sigmoidoscopy as a colorectal cancer screening modality
      should take into account the relatively high rate of incomplete studies,
      particularly in women.

PMID- 9932915
TI  - Restorative proctocolectomy with ileal pouch-anal anastomosis in 203 patients:
      the Auckland experience.
AB  - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
      has become an established operation for patients with ulcerative colitis and
      familial adenomatous polyposis (FAP). The results of a 15-year experience with
      IPAA are reported. METHODS: Between September 1982 and June 1997, 203 patients
      had IPAA surgery. From a review of the charts, data were collected on the
      surgical procedure, the diagnosis and early and late complications. Pouch
      function was assessed by means of a postal questionnaire. RESULTS: Of the 201
      patients (median age of 32 years; 89 women) with complete records, 122 had J
      pouches, 65 had W pouches and 14 S pouches were constructed. The pre-operative
      diagnosis in 88% was ulcerative colitis and in 10% it was FAP. During a median
      follow-up time of 6.1 years the diagnoses were changed for 8% of the patients; in
      4% the diagnosis was changed to Crohn's disease. The overall mortality was 1.5%
      (early = 2, late = 1). The overall morbidity was 62% (early = 17%, late = 52%).
      The pouch was removed or was non-functional in 9%. All patients with a final
      diagnosis of Crohn's disease have had their pouch excised. The median stool
      frequency was 4.0 (range 1.3-8.7) during the day, and 0.7 (range 0-2.1) during
      the night. The fewer night-time stools (J = 1.0+/-0.6; W = 0.4+/-0.5 P < 0.0001)
      and the reduced requirement of the W-pouch patients for anti-diarrhoeals (P =
      0.004) were offset by the need for two W-pouch patients to pass a catheter to
      empty their pouches. CONCLUSIONS: The type of patients who present for IPAA
      surgery and the outcomes observed in this series of Auckland patients are similar
      to those reported from major centres elsewhere.

PMID- 9932916
TI  - Total colectomy for Crohn's disease.
AB  - BACKGROUND: Total colectomy for Crohn's disease of the colon may be restorative
      with ileorectal anastomosis or with an ileostomy and rectal stump. The present
      paper retrospectively audits the results of total colectomy and in particular
      assesses the number of patients who had a permanent ileostomy and whether this
      was related to disease in the rectum at the time of the original operation.
      METHODS: A retrospective case note review was undertaken of patients operated
      upon between 1968 and 1994. RESULTS: Thirty-eight patients were identified (mean
      age 35 years; range 17-65 years). One patient died perioperatively from an
      anastomotic leak. Median follow-up for the remaining patients was 7 years (range
      1-29 years). Ileorectal anastomosis was performed in 17 patients and total
      colectomy and ileostomy in 20 patients. Indications for surgery were failure of
      medical treatment (61%); toxic colitis (18%); abscess (8%); perforation (5%);
      large bowel obstruction (5%); and colovesical fistula (3%). Subsequent
      proctectomy (14 patients, 38%) was more likely with subtotal colectomy and
      ileostomy (nine patients, 45%) than ileorectal anastomosis (five patients, 29%).
      This was not statistically significant (P = 0.33). Additionally, seven patients
      had diversion of the rectum making 21 with an ileostomy (57%). Rectal involvement
      at the time of the original procedure significantly increased the likelihood of
      permanent ileostomy (P = 0.001). The presence of anal disease did not increase
      the prospect of ileostomy. One patient died with advanced adeno carcinoma in a
      defunctioned rectum. CONCLUSIONS: A permanent ileostomy after total colectomy for
      Crohn's disease is common and significantly more likely with rectal involvement.

PMID- 9932918
TI  - Multinodular goitre presenting as a clinical single nodule: how effective is
      hemithyroidectomy?
AB  - BACKGROUND: Patients who present with a single thyroid nodule that requires
      surgery will generally undergo hemithyroidectomy. If, however, the subsequent
      histological examination shows unsuspected multinodular change, there is a risk
      of recurrence in the remain ing lobe. The aim of this study was to determine the
      clinical outcome in patients who have had a hemithyroidectomy for a single
      thyroid nodule that was shown on subsequent histopathological examination to be
      part of a multinodular goitre. METHODS: A survey was undertaken of patients who
      were identified from a thyroid surgery database with the following criteria: (i)
      hemithyroidectomy for clinical single nodule; and (ii) multinodular change on
      histopathology. Main outcome measures were clinical recurrence rate, the
      frequency of further thyroid surgery, and the efficacy of thyroxine treatment on
      recurrence. RESULTS: In the 229 patients studied, the clinical recurrence rate
      was 12%. Fourteen of the 28 patients with recurrence required further surgery.
      Thyroxine therapy did not influence the recurrence rate. CONCLUSION: When surgery
      for a clinically benign single thyroid nodule is indicated, hemithyroidectomy is
      an adequate surgical procedure in cases where the single nodule is subsequently
      found to be part of a multinodular goitre. Such patients can be reassured that
      the chance of clinical recurrence is low. Thyroxine replacement therapy appears
      not to prevent recurrence.

PMID- 9932917
TI  - Insurance and the risk of ruptured appendix in the adult.
AB  - BACKGROUND: Disparities in medical care related to the insurance status of
      patients have been reported. A retrospective analysis was performed to examine
      the insurance-related differences in the risk of appendiceal perforation in the
      Prince of Wales Hospital (POWH), New South Wales. METHODS: Computerized data of
      1179 patient years who had a diagnosis of appendicitis and were admitted to the
      POWH over the preceding 10 years were examined. The outcome measure was
      appendiceal perforation. Patient variables examined were insurance status, sex,
      age, and socio-economic status (SES). Three hundred patients over the same period
      were identified who had an appendicectomy but not appendicitis. Multiple logistic
      regression and Fisher's exact test were used for statistical analysis. RESULTS:
      The overall perforation rate in 1179 patients was 17%. The only factor that was
      related to an increased risk of perforation was age over 50 years (odds ratio
      (OR) 1.57; 95% confidence interval (CI) 1.04-2.53). Sex, insurance status or SES
      were not associated with a higher risk of perforation. The overall rate of
      negative appendicectomy was 20% (300 of 1479 patients), and the rate was higher
      in the uninsured patients (22 vs 17%, P = 0.014, Fisher's exact test).
      CONCLUSIONS: Lack of health insurance was not associated with an increased
      incidence of appendiceal perforation at the POWH. Age over 50 years was
      identified as the only risk factor for appendiceal perforation. The lower
      negative appendicectomy rate in the insured group may be because of better
      diagnostic ability of consultants compared to registrars.

PMID- 9932919
TI  - Five micro-curie urea breath test for the diagnosis of Helicobacter pylori
      infection: evaluation in a South-East Asian population.
AB  - BACKGROUND: Helicobacter pylori is an important pathogen responsible for
      significant morbidity and mortality. Its prevalence varies widely in different
      geographical locations and is especially high in parts of Asia. METHODS: A double
      blind study was carried out to evaluate the use of the 5 microCi (185 KBq) [14C]
      urea breath test ([14C]-UBT) in a South-East Asian population by validating its
      diagnostic accuracy against histology and the CLO test. RESULTS: The sensitivity
      and specificity of the [14C]-UBT was 100% when compared against the CLO test.
      When histology was used as the 'gold standard', the sensitivity and specificity
      were 100% and 97.2%, respectively. There was no overlap or indeterminate values
      between positive and negative results on the [14C]-UBT. CONCLUSIONS: Among South
      East Asian populations where the prevalence of H. pylori infection is high, the
      high sensitivity of the 5 microCi [14C]-UBT makes it a very important test in the
      detection of H. pylori.

PMID- 9932920
TI  - Intermittent self catheterization versus regular outpatient dilatation in
      urethral stricture: a comparison.
AB  - BACKGROUND: The results of regular intermittent self catheterization were
      compared with regular outpatient dilatation after endoscopic internal urethrotomy
      for urethral strictures. METHODS: The records of patients who were treated for
      urethral stricture disease over a 4-year period from 1991 to 1994 were reviewed.
      They were either on regular urethral dilatation or were advised to carry out self
      calibration. A follow-up questionnaire was sent to them and they were asked to
      attend a review. Student's t-test and Proportion Test were used to find out if
      there was any significant difference between the two groups. RESULTS: There were
      78 patients who were on self calibration and 49 patients on regular urethral
      dilatation. There was no significant difference between the two groups regarding
      the duration of follow-up (21.5 and 23.7 months, respectively); the length of
      stricture (1.5 and 1.7 cm, respectively); and complications (two and four,
      respectively). However, patients on self calibration had narrower strictures (4.8
      and 5.7 F) and a significantly lower restricture rate (5 and 16%). The current
      urinary stream was compared to the immediate postoperative stream. This showed
      that a higher number of patients in the dilatation group were voiding at less
      than 25% of their immediate postoperative flow. People from high and low socio
      economic groups were able to carry out self calibration satisfactorily.
      CONCLUSION: Patients from high and low socio-economic groups found that self
      calibration resulted in a lower restricture rate and better stream when compared
      to regular urethral dilatation.

PMID- 9932921
TI  - Prevalence of significant carotid stenosis in Chinese patients with peripheral
      and coronary artery disease.
AB  - BACKGROUND: The prevalence of extracranial carotid stenosis in the Chinese
      population is not known. This study aims to investigate and compare carotid
      disease in several groups of high-risk patients. METHOD: Routine screening
      carotid duplex scans were performed on high-risk Chinese patients without
      cerebrovascular symptoms. These consisted of 249 patients with peripheral
      vascular disease, 207 patients with coronary artery disease, and 45 patients with
      abdominal aortic aneurysm. In addition, 220 patients with cerebrovascular
      symptoms and 58 patients with carotid bruits were scanned. A group of 108 healthy
      individuals was included as a control. The data of all 887 subjects were
      analysed. RESULTS: Carotid stenosis of 70% or greater was detected in 37.7% of
      patients in the cerebrovascular disease group and 24.5% of patients with
      peripheral arterial disease; it was higher than in patients with coronary artery
      disease (11.1%), asymptomatic carotid bruit (10.3%) and aortic aneurysms (8.9%; P
      < 0.001). No significant disease was found in the controls. Patients with
      cerebrovascular disease have more severe degrees of carotid stenosis and
      significantly more total occlusions. Smoking, age and male sex were the main risk
      factors for high-grade (> or = 70%) carotid stenosis. CONCLUSION: The prevalence
      of extracranial carotid stenosis in Chinese patients is not low. Patients with
      peripheral arterial disease have the highest risk of significant carotid
      stenosis: routine carotid duplex screening in these patients is recommended.

PMID- 9932922
TI  - Arterial lesions in severe lower limb ischaemia: a prospective study of 100
      consecutive ischaemic limbs in a Hong Kong Chinese population.
AB  - BACKGROUND: The pattern and distribution of arterial lesions in a local Chinese
      population were studied to assess the feasibility of reconstruction and the
      possibility of avoiding major amputation of ischaemic limbs. METHOD: Between
      March 1995 and August 1997, 90 consecutive patients with 100 severely ischaemic
      lower limbs and their arteriograms were analysed. There were 48 female and 42
      male patients with a mean age of 72 years. All the patients were in fair general
      health, did not have foot pulses and were willing to undergo major arterial
      reconstruction. Ten patients had bilateral limb ischaemia and 94 of the ischaemic
      limbs were affected by rest pain with or without ulcer and/or gangrene. The
      remaining six patients had debilitating claudication. These lesions were
      classified into low-grade (less than 50% stenosis), high-grade (50-90% stenosis)
      and critical (> 90% stenosis to occlusion). RESULTS: Critically stenotic or
      occlusive lesions were present in 16% of aorto-iliac segments; 76% of
      femoropopliteal arteries; and 82% of trifurcation and infrapopliteal segments. In
      at least 27 patients one of the two main foot arteries was also severely
      diseased. The present analysis suggested that 79 of these ischaemic limbs had
      reconstructable lesions. Sixteen were not suitable for intervention and in five
      patients the reconstructability was uncertain radiologically. CONCLUSION:
      Contrary to local belief, the majority of patients in the Chinese community with
      severe lower limb ischaemia without foot pulses would have technically
      reconstructable arterial lesions and could benefit from a revascularization
      procedure.

PMID- 9932923
TI  - In vitro inhibition of tumour growth in a helium-rich environment: implications
      for laparoscopic surgery.
AB  - BACKGROUND: The recent results of several experimental studies have suggested
      that tumour implantation after laparoscopic surgery for intra-abdominal
      malignancy may be partly related to the chemical composition of the insufflation
      gas used during surgery. These studies have demonstrated that the use of helium
      as a laparoscopic insufflation agent for cancer surgery results in less tumour
      implantation and growth at port sites. To further investigate these findings, the
      present study was performed to compare the growth of cultured tumour cells after
      exposure to simulated laparoscopic environments, rich in helium, carbon dioxide
      (CO2), or air. METHODS: A rat mammary adenocarcinoma cell suspension was exposed
      to a simulated laparoscopic environment for 40 min in one of the following
      groups: (i) control (atmospheric air, equivalent to a 'gasless' laparoscopic
      environment); (ii) a CO2-rich environment; and (iii) a helium-rich environment.
      Cells were then cultured for 18 h and optical density readings were used to
      assess the number of viable tumour cells at the end of this period. The
      experiment was performed twice using an identical protocol to ensure consistency
      in the results. In a further study, pH was continuously measured using an
      antimony probe during a 40 min insufflation period and for 10 min after
      insufflation. RESULTS: Cell growth was significantly lower after incubation in
      the helium-rich environment compared to both the CO2 and control groups (P <
      0.001). There was a significant decrease in pH in the CO2 group which was not
      observed during exposure to either air or helium. CONCLUSIONS: The inhibition of
      tumour growth in a helium-rich environment demonstrated by this study, and the
      reduced incidence of port-site metastases seen in other experimental studies,
      suggests that the clinical use of helium as an insufflation gas may have
      important advantages over CO2.

PMID- 9932924
TI  - Communicating bronchopulmonary foregut malformations in the adriamycin-induced
      rat model of oesophageal atresia.
AB  - BACKGROUND: Communicating bronchopulmonary foregut malformations (CBPFM) are rare
      abnormalities of the development of the primitive foregut that result in an
      abnormal communication between the upper gastrointestinal tract and pulmonary
      tissue. They usually occur in isolation, but sometimes are seen in association
      with oesophageal atresia (OA). METHODS: Communicating bronchopulmonary foregut
      malformations were induced in the offspring of pregnant rats by intraperitoneal
      injection of Adriamycin (Delta West Pty Ltd, Bentley, Western Australia,
      Australia). Fetuses harvested by caesarean section were fixed in 10% formalin,
      transversely sectioned and stained with haematoxylin and eosin. Serial
      examination of the slides allowed three-dimensional reconstruction of the anatomy
      of the pulmonary system and the oesophagus. RESULTS: Communicating
      bronchopulmonary foregut malformations occurred in nine (30%) of fetuses with OA.
      Three types of CBPFM were produced: an isolated pulmonary structure (accessory
      lung) attached to the lower oesophagus via a patent bronchus (6 fetuses); an
      anomalous bronchus from the lower oesophagus to the lower part of the left lung
      (two fetuses); and atresia of the trachea (one fetus). CONCLUSIONS: These
      observations are consistent with the assertion that CBPFM and OA are variations
      of a spectrum of abnormalities and may have a similar aetiology. In the rat model
      it would appear that Adriamycin interferes with the timing and progression of
      lung bud differentiation at a time when the primitive foregut is developing
      rapidly. Ultimately, this model may shed light on the embryogenesis of both
      anomalies.

PMID- 9932925
TI  - Endoscopic thoracic sympathectomy for primary palmar hyperhidrosis: intermediate
      term results.
AB  - BACKGROUND: The authors' experience of the efficacy and safety of endoscopic
      thoracic sympathectomy in the treatment of primary palmer hyperhidrosis was
      examined. METHODS: A retrospective study of 71 patients (126 sympathectomies) was
      undertaken. Data were retrieved by hospital records and telephone interview.
      RESULTS: Follow-up was possible for 92 sympathectomies in 53 patients. Overall,
      satisfactory results were achieved in 93% of patients and complications were
      uncommon. Compensatory hyperhidrosis was the most common complication, which
      occurred in 64% of patients; the trunk and feet were the most common sites.
      Horner's syndrome occurred in five patients, although in two it was a permanent
      complication. No patient expressed dissatisfaction with the procedure as a
      consequence of this complication. Pneumothorax occurred in 17.5% of cases,
      although the vast majority were incidental findings on a postoperative chest X
      ray, and none required drainage. With the newer techniques of access, patient
      dissatisfaction with the cosmetic appearance has fallen from 27.3 to 6.4%.
      Overall 90% of patients said they would have the operation again, which
      represents a high level of patient satisfaction. CONCLUSIONS: Endoscopic thoracic
      sympathectomy is a safe and effective technique for primary palmer hyperhidrosis.
      Evolution of the technique has resulted in improvement in patient satisfaction.

PMID- 9932926
TI  - On-the-table colonic lavage.
AB  - Single-stage surgery is an acceptable option in the modern management of many
      acute colonic conditions. Anastomosing unprepared colon is a major concern. A
      technique is described that allows on-the-table colonic lavage to be performed
      without contamination of the abdominal cavity.

PMID- 9932927
TI  - Prediction of survival in the individual with breast cancer.

PMID- 9932928
TI  - Single-versus multiple-dose antimicrobial prophylaxis for major surgery: comment.

PMID- 9932929
TI  - Carcinoid tumour of the spleen.

PMID- 9932930
TI  - Apocrine ductal carcinoma in situ of the breast presenting as a chronic abscess.

PMID- 9932931
TI  - Idiopathic scrotal lymphoedema in Down's syndrome.

PMID- 9932932
TI  - Tracheal obstruction after insertion of a self-expanding oesophageal stent.

PMID- 9932933
TI  - Caecal volvulus after laparoscopic cholecystectomy.

PMID- 9932934
TI  - Evaluating dementia screening tests: methodologic standards to rate their
      performance.

PMID- 9932935
TI  - Neurology "with the bark off": tacrine, nursing home residents, and health
      services research.

PMID- 9932936
TI  - Screening for dementia with the memory impairment screen.
AB  - OBJECTIVES: To validate a sensitive and specific screening test for AD and other
      dementias, assess its reliability and discriminative validity, and present
      normative data for its use in various applied settings. BACKGROUND: To improve
      discrimination in screening for AD and dementia, we developed the Memory
      Impairment Screen (MIS), a 4-minute, four-item, delayed free- and cued-recall
      test of memory impairment. The MIS uses controlled learning to ensure attention,
      induce specific semantic processing, and optimize encoding specificity to improve
      detection of dementia. METHODS: Equivalent forms of the MIS were given at the
      beginning and end of the testing session to assess alternate forms reliability.
      Discriminative validity was assessed in a criterion sample of 483 aged
      individuals, 50 of whom had dementia according to Diagnostic and Statistical
      Manual of Mental Disorders (3rd ed., revised) criteria. RESULTS: The MIS had good
      alternate forms reliability, high construct validity for memory impairment, and
      good discriminative validity in terms of sensitivity, specificity, and positive
      predictive value. We present normative data for use in settings with different
      base rates (prevalences) of AD and dementia. CONCLUSION: The MIS provides
      efficient, reliable, and valid screening for AD and other dementias.

PMID- 9932937
TI  - Tacrine use in nursing homes: implications for prescribing new cholinesterase
      inhibitors. SAGE Study Group. Systematic Assessment of Geriatric Drug Use via
      Epidemiology.
AB  - OBJECTIVE: To describe the use of tacrine in nursing home residents using data
      from a clinically based resident assessment instrument used by all US nursing
      homes. METHODS: Data were from the Systematic Assessment of Geriatric Drug Use
      via Epidemiology (SAGE) database, a population-based data set with information on
      329,520 patients admitted to all Medicare/Medicaid certified nursing homes in
      four US states (Maine, Mississippi, New York, and South Dakota) from 1992 through
      1995. The SAGE database combines information from the Minimum Data Set (MDS) and
      the On-Line Survey and Certification Automated Record. We identified all
      residents receiving tacrine and up to five control residents per case matched on
      state, date of tacrine use, cognitive function, and dementia diagnosis. RESULTS:
      A total of 1,640 (0.5%) nursing home residents received tacrine at least once.
      Only 38% of these residents had a diagnosis of AD documented on the MDS;
      regardless of dementia diagnosis, 25% had severe cognitive impairment, 35% were
      severely dependent in activities of daily living (ADL), and 17% had both severe
      cognitive and ADL impairment. Only 8% achieved a therapeutic dose of at least 120
      mg/d. After adjusting for confounding variables, wandering and being physically
      abusive were the strongest predictors of tacrine use. CONCLUSIONS: A minority of
      nursing home residents received tacrine. Of those who did, a significant
      proportion were unlikely to benefit from its use because of their level of
      cognitive and ADL impairment, or because low doses were used. As new medications
      become available for dementia, MDS data can be used by nursing homes to monitor
      the use of these therapies.

PMID- 9932938
TI  - Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of
      traumatic brain injury.
AB  - OBJECTIVE: To determine the ability of apolipoprotein E (APOE) genotypes to
      predict days of unconsciousness and a suboptimal functional outcome in traumatic
      brain injury (TBI) survivors. BACKGROUND: TBI is known to be associated with
      neuropsychological deficits and functional disability. Recent evidence indicates
      that APOE plays a pivotal role in CNS response to injury. METHODS: In this
      prospective study the authors determined the APOE genotypes and tested their
      ability to predict days of unconsciousness and functional outcome after at least
      6 months in 69 survivors of TBI. A good functional outcome was defined as no
      dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive
      abnormalities; and the ability to live independently. RESULTS: The odds ratio of
      more than 7 days of unconsciousness was 5.69 in those with the APOE-epsilon4
      allele compared with those without the epsilon4 allele (95% CI, 1.69 to 20.0; p =
      0.001). Only 1 of 27 subjects (3.7%) with the epsilon4 allele had a good
      functional outcome compared with 13 of 42 (31.0%) of those without the epsilon4
      allele (p = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was
      13.93 for those with the epsilon4 allele compared with those without the allele
      after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; p
      = 0.02). CONCLUSION: The results demonstrate a strong association between the
      APOE-epsilon4 allele and a poor clinical outcome, implying genetic susceptibility
      to the effect of brain injury. Additional studies of TBI patients are warranted
      to confirm their findings.

PMID- 9932939
TI  - Disproportion in the distribution of gray and white matter: neuropsychological
      correlates.
AB  - OBJECTIVE: To examine the relationship between measures of disproportion in the
      regional distribution of gray and white matter and preoperative
      neuropsychological function in temporal lobe epilepsy patients with proved
      hippocampal sclerosis (HS). BACKGROUND: Subtle cerebral structural disruption,
      not evident on routine inspection of high-resolution MRI, is associated with poor
      surgical outcome in patients with histologically proved HS. Preoperative global
      memory dysfunction is also associated with poor postoperative seizure control.
      The authors hypothesize that patients with HS and abnormal regional distributions
      of gray and white matter would show more diffuse neuropsychological deficits
      preoperatively than patients with isolated HS alone. METHODS: A total of 28
      adults with lateralized temporal lobe epilepsy and hippocampal volume loss
      measured on MRI were assessed preoperatively on neuropsychological tests of
      general intellect and the learning and recall of both verbal and nonverbal
      material. Quantitative MRI analysis of the regional distribution of gray and
      white matter was performed. Chi-square analyses were used to examine the relation
      between the presence or absence of cerebral abnormalities and preoperative
      performance on the neuropsychological tests. RESULTS: A total of 15 of 28
      patients had extrahippocampal abnormalities on quantitative MRI analysis.
      Thirteen patients had global memory impairment. Bilateral memory deficits were
      significantly associated with both the presence of cerebral abnormalities (p <
      0.02) and poor postoperative seizure control (p < 0.05). CONCLUSIONS:
      Disproportion in the regional distribution of gray and white matter in patients
      with HS may form the structural basis of global memory disturbance in a distinct
      group of patients with temporal lobe epilepsy.

PMID- 9932940
TI  - JC virus DNA load in patients with and without progressive multifocal
      leukoencephalopathy.
AB  - OBJECTIVE: To determine the clinical value of JC virus (JCV) detection in various
      anatomic compartments for the diagnosis of progressive multifocal
      leukoencephalopathy (PML). METHODS: CSF, peripheral blood mononuclear cells
      (PBMC), plasma, and urine samples were evaluated from HIV-infected and uninfected
      individuals. JCV DNA was detected by PCR and was quantified using a competitive
      PCR ELISA. RESULTS: JCV DNA was detected in one-third of the urine samples,
      regardless of HIV serostatus or clinical evidence of PML. JCV DNA was detected in
      five of eight PBMC and three of seven plasma samples of HIV-positive PML
      patients, in 13 of 103 PBMC and 7 of 32 plasma samples of HIV-positive persons
      without PML, but in 0 of 18 PBMC and 0 of 13 plasma samples of HIV-negative
      control subjects. There was no correlation between the presence of JCV DNA in the
      PBMC and plasma, but the detection of JCV in either compartment was associated
      with low CD4+ lymphocyte counts. JCV DNA was not detected in the CSF of 27 of 27
      HIV-negative persons and 64 of 65 HIV-positive persons without PML, but was found
      in the CSF of three of three HIV-negative immunosuppressed individuals and 10 of
      11 HIV-positive individuals with clinical and radiologic evidence of PML,
      confirmed by biopsy in four of four tested patients. PBMC harbored 10 to 90 JCV
      copies/microg DNA, and the CSF of the PML patients contained 3.65 x 10(4) to 2.04
      x 10(5) JCV copies/mL CSF. CONCLUSIONS: JCV viruria was found as frequently in
      HIV-positive individuals as in control subjects, suggesting that its detection
      has no clinical value. JCV detection in the blood correlates with
      immunosuppression and not with PML. The presence of JCV in the CSF is highly
      sensitive and specific for PML, and a high CSF JC viral load was associated with
      poor clinical outcome in patients receiving antiretroviral therapy. JCV
      quantification in the CSF constitutes a potentially important tool for monitoring
      clinical PML treatment trials.

PMID- 9932941
TI  - Involvement of the spinal posterior horn in Gerstmann-Straussler-Scheinker
      disease (PrP P102L).
AB  - OBJECTIVE: The authors studied the pathomechanisms of the characteristics
      associated with Gerstmann-Straussler-Scheinker disease (GSS). BACKGROUND: GSS,
      associated with a missense mutation at codon 102 of the prion protein (PrP) gene
      (GSS102), is a hereditary disorder that presents with progressive ataxia and
      dementia, and is characterized by the loss of deep tendon reflexes and painful
      dysesthesias of the legs in its early stage. METHODS: The authors conducted
      immunohistochemical studies of the spinal cord and peripheral nervous system in
      one of two patients from a Japanese family with GSS102 in comparison with
      patients with GSS105. RESULTS: The authors found intense PrP immunoreactivities
      mainly in the posterior horn of the spinal cord, but not in the dorsal root
      ganglia or peripheral nerves. In addition to PrP amyloid plaques, synaptic-type,
      fine granular PrP deposits were distributed in the spinal posterior horns. In
      contrast to the GSS102 patient, the spinal cords of the GSS105 patients showed no
      granular PrP deposits. CONCLUSIONS: The PrP abnormalities in synaptic structures
      of the spinal posterior horn may cause synaptic dysfunction that leads to loss of
      deep tendon reflexes and painful dysesthesias in patients with GSS102.

PMID- 9932942
TI  - No evidence for an ischemic penumbra in massive experimental intracerebral
      hemorrhage.
AB  - OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on
      regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis
      that there is persistent ischemia in the perihematoma region after ICH.
      BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural
      injury after ICH. Presumably the hematoma induces ischemia by mechanical
      compression of the surrounding microvasculature. METHODS: The authors induced ICH
      in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under
      arterial pressure in the deep white matter adjacent to the left basal ganglia.
      They measured serial rCBF using radiolabeled microspheres in regions around and
      distant to the hematoma, as well as cerebral oxygen extraction, oxygen
      consumption (CMRO2), glucose utilization, and lactate production by serial
      sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure
      (MAP) and intracranial pressure (ICP) were monitored continuously. All
      measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction
      of ICH and compared with prehematoma values. Evans Blue dye was injected at the
      end of the experiment, and intensity of staining was compared with three control
      animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/
      standard error), significant elevation in ICP was observed after ICH peaking at 5
      hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg),
      significant elevation in MAP was observed at 120 minutes after onset of hematoma
      (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were
      no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus
      44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours
      posthematoma (or any other posthematoma measurement) compared with prehematoma
      values. There were no significant differences observed in rCBF in the
      perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or
      white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours
      posthematoma (or any other posthematoma measurement) compared with prehematoma
      values. No changes were observed in cerebral glucose utilization, lactate
      production, and rCBF in other regions after introduction of ICH. Permeability of
      the blood-brain barrier was more prominent in the ipsilateral hemisphere in
      animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent
      increase in ICP and MAP after ICH, the authors found no evidence to support the
      presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other
      mechanisms for acute neural injury and late rCBF changes after ICH must be
      investigated.

PMID- 9932943
TI  - Increased therapeutic efficacy with rt-PA and anti-CD18 antibody treatment of
      stroke in the rat.
AB  - OBJECTIVE: To examine the efficacy of an antileukocyte adhesion antibody (anti
      CD18) as an adjuvant for delayed (2 hours and 4 hours) thrombolytic therapy
      (recombinant human tissue plasminogen activator [rt-PA]) in middle cerebral
      artery occlusion (MCAO) in rats. BACKGROUND: Thrombolytic therapy with rt-PA is
      limited in its application by a short therapeutic window. METHODS: Male Wistar
      rats were subjected to MCAO by a single fibrin-rich clot. The rats were assigned
      to the following experimental groups: Experiment 1 (treatment 2 hours after
      embolization), 1) rt-PA, 2) anti-CD18 antibody, 3) rt-PA and anti-CD18 antibody,
      4) immunoglobulin (Ig) G, and 5) vehicle; Experiment 2 (treatment 4 hours after
      occlusion), 1) rt-PA alone, 2) rt-PA and anti-CD18 antibody, and 3) nontreated
      control group. Neurologic deficits, infarction volume, hemorrhage, and brain
      myeloperoxidase (MPO) immunoreactivity were measured. RESULTS: Administration of
      rt-PA and anti-CD18 antibody 2 hours later reduced significantly (p < 0.05) the
      infarct volume and improved neurologic deficits compared with the vehicle-treated
      group. Treatment with rt-PA alone improved neurologic deficits significantly and
      reduced mean infarct volume compared with the vehicle-treated group. However,
      treatment with anti-CD18 antibody neither reduced infarct volume nor improved
      neurologic deficits compared with the IgG-treated group. The combination of rt-PA
      and anti-CD18 antibody treatment at 4 hours reduced significantly the infarct
      volume and MPO immunoreactive cells compared with rt-PA treatment alone at 4
      hours, and reduced neurologic deficits compared with rt-PA treatment alone and
      compared with the nontreated animals. CONCLUSIONS: The combination of
      antileukocyte adhesion antibody and thrombolytic therapy may increase the
      therapeutic window for the treatment of stroke.

PMID- 9932944
TI  - Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in
      Acute Stroke Treatment (TOAST) Investigators.
AB  - OBJECTIVE: To study the relation between acute blood glucose level and outcome
      from ischemic stroke. BACKGROUND: Hyperglycemia may augment acute ischemic brain
      injury and increase the risk of hemorrhagic transformation of the infarct.
      METHODS: The authors analyzed the relation between admission blood glucose level
      (within 24 hours from ischemic stroke onset) and clinical outcome in 1,259
      patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)-a
      placebo-controlled, randomized, double-blind trial to test the efficacy of a low
      molecular weight heparinoid in acute ischemic stroke. Very favorable outcome was
      defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19
      or 20. Neurologic improvement at 3 months was defined as a decrease by > or =4
      points on the NIH Stroke Scale compared with baseline or a final score of 0.
      Hemorrhagic transformation of infarct was assessed within 10 days after onset of
      stroke with repeat cerebral CT. Stroke subtype as lacunar or nonlacunar
      (atherothromboembolic, cardioembolic, and other or undetermined etiology) was
      classified by one investigator after completion of stroke evaluation according to
      study protocol. RESULTS: In all strokes combined (p = 0.03) and in nonlacunar
      strokes (p = 0.02), higher admission blood glucose levels were associated with
      worse outcome at 3 months according to multivariate logistic regression analysis
      adjusted for stroke severity, diabetes mellitus, and other vascular risks. In
      lacunar strokes, the relationship between acute blood glucose level and outcome
      was related to treatment. In the placebo group, higher admission blood glucose
      levels were associated with better outcome at 3 months. However, in the active
      drug group, as the glucose level increased from 50 to 150 mg/dL, the probability
      of a very favorable outcome decreased sharply and remained relatively unchanged
      as the glucose level increased further (p = 0.002, for overall effect of glucose
      on outcome). Acute blood glucose level was not associated with symptomatic
      hemorrhagic transformation of infarcts or with neurologic improvement at 3
      months. CONCLUSIONS: During acute ischemic stroke hyperglycemia may worsen the
      clinical outcome in nonlacunar stroke, but not in lacunar stroke, and is not
      associated with an increased risk of hemorrhagic transformation of the infarct.

PMID- 9932945
TI  - A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs
      syndrome with late-night symptoms.
AB  - OBJECTIVE: To investigate whether a combination treatment of regular-release
      levodopa (rr-L-dopa) and sustained-release levodopa (sr-L-dopa) compared with
      monotherapy of rr-L-dopa improves sleep quality and reduces periodic limb
      movements (PLM) in patients with restless legs syndrome (RLS) and problems with
      maintaining sleep. BACKGROUND: Reappearance of RLS symptoms during the second
      half of the night while being treated with rr-L-dopa is a common problem in the
      treatment of sleep disturbances caused by RLS. METHODS: A randomized, controlled,
      double-blind crossover trial was undertaken. Eligible patients fulfilled the
      diagnostic criteria of the International RLS Study Group, and met an
      actigraphically confirmed higher number of PLM per hour time in bed (PLM index)
      during the second half compared with the first half of the night under treatment
      with rr-L-dopa. During the crossover periods the patients received 100 to 200 mg
      rr-L-dopa plus either placebo or 100 to 200 mg sr-L-dopa at bedtime for 4 weeks
      each period. RESULTS: Thirty patients with RLS (11 men and 19 women) were
      assessed by actigraphy and subjective sleep quality, and showed a significant
      improvement in PLM index (p < 0.0001), in "time in bed without movements" (p <
      0.0001), and in subjective sleep quality (p < 0.001). Eight of 30 patients
      reported an altered pattern of RLS symptoms, characterized by a time shift of RLS
      symptoms into the afternoon or evening, five of these during monotherapy with rr
      L-dopa. CONCLUSIONS: A combination therapy of rr-L-dopa and sr-L-dopa is better
      than monotherapy with rr-L-dopa in reducing the frequency of PLM and problems
      maintaining sleep, even in patients who are severely affected.

PMID- 9932946
TI  - Diminished regional cerebral blood flow response to vibration in patients with
      blepharospasm.
AB  - OBJECTIVE: To determine whether patients with blepharospasm have abnormal
      sensorimotor processing similar to patients with writer's cramp. BACKGROUND:
      Blepharospasm is a focal dystonia manifest by involuntary, excessive blinking and
      squeezing of the eyes. Altered sensorimotor processing may contribute to the
      development of dystonic movements. Previously the authors demonstrated decreased
      vibration-induced cortical blood flow responses in hand primary sensorimotor area
      (PSA) in patients with hand dystonia. METHODS: In this prospective, case-control
      study, seven patients with blepharospasm were compared with seven normal
      subjects. PET measurements of regional blood flow were obtained using bolus
      administration of H(2)15O at rest or during sequential vibration of either the
      left or the right hand or side of the mouth. RESULTS: PSA activation decreased
      significantly in the patients with blepharospasm both ipsilateral (-68%; p =
      0.0004) and contralateral to the side of facial stimulation (-56%; p = 0.0009).
      Patients had a 31% lower mean contralateral PSA response to hand vibration and a
      51% smaller right supplementary motor area response to left-hand vibration than
      normal subjects, but these differences did not reach statistical significance.
      CONCLUSIONS: Patients with blepharospasm have abnormal sensorimotor processing in
      response to lower face vibration. They may also have abnormal brain responses to
      stimulation of clinically uninvolved parts of the body, but this requires
      confirmation.

PMID- 9932947
TI  - Alpha1-antichymotrypsin gene polymorphism and susceptibility to Parkinson's
      disease.
AB  - OBJECTIVE: To determine whether the alpha1-antichymotrypsin AA genotype (ACT-AA)
      confers susceptibility for developing Parkinson's disease (PD) in the Spanish
      population. BACKGROUND: A correlation between the ACT-AA genotype and the risk of
      developing PD has been recently reported in the Japanese population. METHODS: The
      ACT genotypes of 71 patients diagnosed with clinically definite PD were compared
      with those of 109 age-matched healthy control subjects. RESULTS: The authors
      found that the ACT-AA polymorphism frequency was not increased significantly in
      the PD group (31%) compared with the control group (28.4%). The ACT allelic
      distribution was also similar for familial and sporadic PD, for female and male
      patients, and for the different clinical subtypes of PD. The age at onset of PD
      was significantly lower in the ACT-AA patients compared with non-ACT-AA patients.
      When the actual age was considered, the ACT-AA frequency was higher in PD
      patients < or =50 years old (50%) compared with that present in patients >50
      years old (26.8%), but the same effect was found in control subjects.
      CONCLUSIONS: The ACT-AA polymorphism is not related to an increased risk of
      developing PD in the Spanish population. The ACT-AA overrepresentation in PD and
      control subjects < or =50 years old suggests that this polymorphism could be
      associated with life-threatening conditions other than PD.

PMID- 9932948
TI  - Changing epidemiology of Parkinson's disease in southwestern Finland.
AB  - OBJECTIVE: Investigation of the epidemiology of PD in southwestern Finland in
      1992 (population 196,864), including urban and rural areas, with a comparison
      with a similar study, done in the same area in 1971, to evaluate the temporal
      pattern. METHODS: Community-based method of patient ascertainment with personal
      investigation of cases. RESULTS: The age-adjusted prevalence (to the Finnish
      general population in 1991) was 139 per 100,000 population in 1971 and 166 in
      1992. Prevalence ratio for PD in men versus women was 1.2 (NS) in 1971 and 1.7 in
      1992 (p < 0.001); in the rural versus urban populations the prevalence ratio was
      0.8 (NS) in 1971 and 1.3 in 1992 (p = 0.013). The age-specific prevalence rates
      showed a male preponderance in all age groups in 1992 and a rural preponderance
      in the age groups over 60 years. In 1992, compared with 1971, the male and rural
      preponderance occurred in the age groups over 70 years. The age-adjusted
      incidence was 15.7 per 100,000 population in 1971 and 14.9 in 1992. Relative risk
      for PD in men versus women was 0.9 (NS) in 1971 and 1.9 (p < 0.001) in 1992, and
      in rural versus urban populations 1.4 (p = 0.093) in 1992. CONCLUSIONS: A very
      significant male and a significant rural predominance, not seen in 1971, suggests
      a possible environmental causative factor, perhaps more frequent in the rural
      environment, associated with PD. Men may be either more exposed to it or more
      susceptible to its effects than women.

PMID- 9932949
TI  - Influence of family history on clinical expression of Tourette's syndrome.
AB  - OBJECTIVE: To determine the influence of family history on clinical expression of
      Tourette's syndrome (TS). BACKGROUND: Recent studies have suggested that clinical
      expression of TS is similar among sporadic (SP) and familial patients but may be
      influenced by bilineal (BIL) transmission of tics or obsessive-compulsive
      behavior (OCB) in high-density pedigrees. METHODS: The authors used family
      history methodology, supported by direct examination of affected relatives in 73%
      of familial patients, to determine the frequency of SP TS, and of unilineal (UNL)
      and BIL transmission of tics or OCB in 111 consecutively ascertained juvenile TS
      patients. For individuals in each group, severity of tics, attention deficit
      hyperactivity disorder (ADHD), and OCB were assessed at presentation and after a
      mean follow-up interval of 2.6 years, using the Tourette's Syndrome Global Scale
      and the Clinical Global Impression scales. The phenomenology of OCB was evaluated
      using the symptom checklist of the Children's Yale-Brown Obsessive Compulsive
      Scale. RESULTS: The authors documented BIL transmission of tics in seven patients
      (6%). Patient age and sex were similar for the SP (n = 21; 19%), UNL (n = 66;
      59%), and BIL (n = 24; 22%) groups, as was ADHD and tic severity at presentation
      and follow-up. Severity of OCB differed significantly between groups, with
      moderate to severe OCB affecting 5% of SP, 12% of UNL, and 37% of BIL patients at
      presentation (p = 0.007), and 5% of SP, 17% of UNL, and 54% of BIL patients at
      follow-up (p = 0.0001). Relative to UNL or SP patients, BIL patients were more
      likely to exhibit self-injurious behaviors (p = 0.0005). CONCLUSIONS: OCB is less
      prominent in SP than in familial TS, perhaps reflecting a more restricted
      pathophysiology in this subgroup. Although BIL transmission of tics is relatively
      infrequent in consecutive TS pedigrees, cotransmission of OCB from an otherwise
      unaffected parent is common and significantly influences development of OCB and
      self-injurious behaviors, but not tics, in offspring. Genetic heterogeneity,
      epigenetic factors, and gene-environment interactions may play a more important
      role than genetic dosage effects in determining tic severity in TS.

PMID- 9932950
TI  - The use of "clinic room" presentation as an educational tool in the ambulatory
      care setting.
AB  - OBJECTIVE: To evaluate the utility of "clinic room" case presentation in the
      ambulatory care setting. BACKGROUND: Neurology is increasingly an outpatient
      specialty. The transition from ward to clinic presents challenges for student and
      resident education. Interaction between attending physician and trainee is
      limited by busy patient schedules. New educational strategies must be developed
      to address the particular challenges of the outpatient clinic. One strategy to
      increase the quality and length of attending-trainee interaction is case
      presentation in the patient's presence. METHODS: The authors randomized 100
      patients seen in an academic neuromuscular clinic to presentation in a conference
      room or clinic room. In the latter, all interaction between the trainee and
      attending occurred in the patient's presence. The attending recorded the time
      spent with the trainee and patient. The patient was asked to complete a survey
      and provide certain demographic information. RESULTS: The two groups were similar
      demographically. Time spent by the attending physician was similar between the
      two settings. Although there was no difference in patient satisfaction, those
      randomized to clinic room presentation were significantly more likely (p < 0.002)
      to feel their questions were answered adequately. There were trends toward these
      patients feeling less embarrassed, feeling that they were treated respectfully,
      and feeling that adequate time was spent with them. CONCLUSIONS: Although clinic
      room presentation does not save attending time, it allows for a more dynamic and
      intensive interaction among teacher, student, and patient.

PMID- 9932952
TI  - Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and
      histopathologic study.
AB  - OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT)
      abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We
      reviewed the MR scans and clinical histories of 50 consecutive patients with
      intractable TLE. Histopathology was available in 42 surgically treated cases.
      RESULTS: MRI demonstrated loss of the gray-white matter differentiation and
      decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of
      the 50 patients. This appearance was observed in 64% of the 36 patients with
      hippocampal sclerosis (HS) but was also seen in patients without HS. These
      changes were associated with temporal lobe atrophy, a higher hippocampal T2
      relaxation time, and a history of febrile convulsions. Pathologic examination
      showed that the MRI appearances were not caused by dysplasia, degenerative
      abnormalities, or inflammatory change. Histologic quantitation showed increased
      glial cell nuclei counts in the intractable TLE cases compared with controls.
      There was no difference in glial cell numbers between cases with AT abnormality
      and those without this appearance. Presence or absence of changes was not
      predictive of preoperative neuropsychology, postoperative change in
      neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently
      seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific
      increase in water content in the temporal lobe. This may be due to myelin
      abnormalities or some other as yet unidentified pathologic factor.

PMID- 9932951
TI  - Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young
      adults.
AB  - OBJECTIVE: To study the acute and steady-state cognitive effects of three new
      antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. BACKGROUND:
      Several newer antiepileptic medications approved recently by the Food and Drug
      Administration are gaining attention as efficacious alternatives to established
      AEDs. Greater tolerability with fewer side effects are reported in some. However,
      the potential cognitive effects of these newer AEDs have received limited
      attention. METHODS: Healthy young adults randomized to either of the three drugs
      were administered tests of attention, psychomotor speed, language, memory, and
      mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on
      the drug. RESULTS: Compared with baseline, the topiramate group had selective,
      statistically significant declines on measures of attention and word fluency at
      acute doses, whereas the other two AED groups had no performance changes. At the
      2- and 4-week test periods, only the topiramate subjects continued to display
      neurocognitive effects from drug administration. CONCLUSIONS: Results demonstrate
      potential acute and steady-state adverse cognitive effects for topiramate,
      whereas minimal effects were displayed for either gabapentin or lamotrigine in
      young healthy adults.

PMID- 9932953
TI  - Evidence for nodular epileptogenicity and gender differences in periventricular
      nodular heterotopia.
AB  - OBJECTIVE: To determine whether clinical differences between the sexes seen in
      periventricular nodular heterotopia (PNH) have structural correlates on imaging.
      BACKGROUND: PNH is the most common dysgenesis associated with hippocampal
      sclerosis (HS). Women with PNH have normal intellect; men may have mental
      retardation and other changes. Familial PNH, seen in women, is linked to Xq28-a
      region also abnormal in a sporadic male infant with PNH and retardation
      suggesting sexual differences in gene expression. Epilepsy associated with PNH
      may be refractory to drugs, and surgery for associated HS does not stop seizures,
      suggesting intrinsic epileptogenicity of PNH. METHODS: Quantitative MRI analysis
      was performed using established techniques for detecting subtle structural
      changes in 13 female patients (11 sporadic and two familial) and four male
      patients (sporadic). RESULTS: There is structural heterogeneity in PNH, even in
      patients with bilateral PNH. On MRI, men have more cerebral abnormalities beyond
      PNH than control subjects or female patients (p < 0.005). CONCLUSIONS: The
      findings support the concept of intrinsic epileptogenicity of PNH. There may be
      additional structural abnormalities relevant to seizure generation, especially in
      men. Structural heterogeneity, and widespread abnormalities, may need
      consideration when patients are referred for surgical treatment or when
      additional studies of patients with PNH are conducted.

PMID- 9932954
TI  - Periventricular leukomalacia and epilepsy: incidence and seizure pattern.
AB  - OBJECTIVE: To study the incidence and pattern of epilepsy in patients with
      periventricular leukomalacia (PVLM) in two specialty clinic settings. BACKGROUND:
      Motor and cognitive deficit as well as epilepsy are common in patients with PVLM.
      With modern imaging techniques, PVLM is now easily recognized. METHODS: Epileptic
      seizures and syndromes as well as motor and cognitive deficits were correlated
      with MRI findings. Two patient populations were studied: Group A-children with
      cerebral palsy and PVLM presenting to a center for children with motor disability
      (n = 19); and Group B-epileptic patients with PVLM presenting to a tertiary
      epilepsy center (n = 12). A single patient with PVLM and epilepsy who underwent
      extensive investigations, including intracranial EEG telemetry, is reported.
      RESULTS: In Group A, 47% of patients had epilepsy (9/19). PVLM was found in 1.27%
      of patients investigated for epilepsy at a tertiary epilepsy center (12/942). The
      majority of patients in both groups had multiple seizure types, with complex
      partial seizures being most common. Of patients with seizures (Groups A and B),
      85.7% had intractable epilepsy (18/21). Intracranial EEG in the illustrative case
      demonstrated a multifocal epileptic process with occipitotemporal predominance.
      CONCLUSIONS: PVLM was an uncommon underlying cause in patients presenting with
      epilepsy (Group A); however, patients presenting with motor disability and PVLM
      (Group B) had a high incidence of seizures. PVLM in epileptic patients is
      associated with multiple seizure types and medically refractory disease.

PMID- 9932955
TI  - Eliprodil stimulates CNS myelination: new prospects for multiple sclerosis?
AB  - OBJECTIVE: To examine the potential of eliprodil-a neuroprotective agent with a
      high affinity for sigma-receptors-to promote myelination in neuron
      oligodendrocytes cocultures. BACKGROUND: Remyelination is one of the major
      therapeutic issues in MS. Because neuronal integrity is required for CNS
      myelination, the authors postulated that neuroprotective molecules might favor
      myelination. METHODS: Two experimental culture conditions were compared: standard
      medium Bottenstein and Sato ([B-S] medium) and a medium depleted of both thyroid
      hormones and progesterone (depleted [D] medium). Myelination was quantified by
      counting the number of myelinated internodes, identified immunocytochemically
      with an antimyelin basic protein (anti-MBP) antibody. RESULTS: The authors first
      confirmed that in D medium myelination was reduced by a factor of 3.5 compared
      with cultures maintained in B-S medium. Under both culture conditions, addition
      of 10(-6) M eliprodil did not modify significantly the total number of either
      microtubule associated protein-2-positive neurons or MBP-positive
      oligodendrocytes. However, eliprodil induced a twofold (p < 0.01) increase in
      myelination when added to B-S medium, and a 4.7-fold (p < 0.0001) increase when
      added to D medium. CONCLUSION: Although the molecular mechanism mediating the
      effect of the sigma-receptor agonist on myelination remains to be elucidated,
      these results strongly suggest that neuroprotective molecules may be of
      therapeutic interest in demyelinating diseases such as MS.

PMID- 9932956
TI  - Natural killer cells in relapsing-remitting MS: effect of treatment with
      interferon beta-1B.
AB  - OBJECTIVE: To determine the effect of treatment with interferon beta-1b (IFN
      beta) on natural killer (NK) cell function and phenotype in relapsing-remitting
      MS (RRMS) patients, and their relationship to disease activity assessed both
      clinically and with serial MRI. BACKGROUND: NK cells may play a role in the
      immunopathogenesis of MS. Previously the authors reported a positive relationship
      between mean NK cell functional activity (FA) and total number of active lesions
      on MRI in a serial study of RRMS. Cycles in NK cell FA over time created a series
      of peaks and valleys, and a significant relationship has been identified between
      the valleys and the appearance of active lesions on MRI or onset of clinical
      attacks. The development of valleys in NK cell FA before the appearance of active
      lesions on MRI was statistically significant. METHODS: The authors studied the
      effect of alternate-day therapy with 8.0 mIU (high dose [HD]) or 1.6 mIU (low
      dose [LD]) IFN-beta on NK cell FA, assessed by an in vitro 51Cr release K-562
      target cell assay, and phenotype determination in RRMS patients. RESULTS:
      Treatment with HD IFN-beta results in an inverse relationship between mean NK
      cell FA and total number of active lesions on MRI over 2 years. A stronger
      inverse relationship was found in those patients who did not develop neutralizing
      antibodies to IFN (HD-) compared with a positive relationship in those who did
      (HD +). Treatment with IFN-beta did not affect the cyclic nature of NK cell FA,
      mean NK cell FA, variability around the mean, mean length of the cycle, time
      spent in valleys and peaks, or the significant relationship between the
      appearance of active lesions on MRI/onset of clinical attacks and valleys in NK
      cell FA. In contrast, treatment with HD but not LD IFN-beta did result in a
      significant reduction in CD57+ (a cell surface marker for subsets of NK cells)
      peripheral blood lymphocytes (PBL) compared with placebo. This effect, which
      originated largely from the HD- group of patients, developed shortly after
      treatment was initiated and was maintained throughout the study. CONCLUSIONS:
      RRMS patients with higher mean NK cell FA may be not only at greater risk for the
      development of active lesions but also may be more likely to respond to IFN-beta.
      Development of neutralizing antibodies to IFN-beta could interfere with this
      effect. This effect may be mediated through an action on a CD57+ subset of PBL.

PMID- 9932957
TI  - Delayed classic and protracted phenotypes of compound heterozygous juvenile
      neuronal ceroid lipofuscinosis.
AB  - OBJECTIVE: To correlate the phenotypes with the genotypes of 10 Finnish juvenile
      neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) patients who all
      are compound heterozygotes for the major 1.02-kb deletion in the CLN3 gene.
      METHODS: The mutations on the non-1.02-kb deletion chromosomes were screened in 6
      patients; in the other 4 patients the mutations were known (one affecting a
      splice site, two missense mutations, and one deletion of exons 10 through 13).
      Clinical features were examined, and MRI, MRS, somatosensory evoked magnetic
      field (SEF), and overnight polysomnography (PSG) studies were performed. RESULTS:
      A novel deletion of exons 10 through 13 was found in 6 patients belonging to
      three families. In the patients carrying the deletions of exons 10 through 13 the
      clinical course of the disease was fairly similar. Variation was greatest in the
      time course to blindness. In these patients the mental and motor decline was
      slower than in classic JNCL, but more severe than in the two patients with
      missense mutations in exons 11 and 13. MRI showed brain atrophy in 4 patients.
      One patient had hyperintense periventricular white matter, otherwise brain signal
      intensities were normal. SEFs were enhanced in patients older than 14 years,
      whereas in PSG all but the youngest 6-year-old patient showed epileptiform
      activity in slow-wave sleep. CONCLUSIONS: JNCL can manifest as at least three
      different phenotypes: classic, delayed classic, and protracted JNCL with
      predominantly ocular symptoms. Finnish compound heterozygotes have the delayed
      classic or the protracted form of JNCL.

PMID- 9932958
TI  - Short-chain acyl-CoA dehydrogenase deficiency: a cause of ophthalmoplegia and
      multicore myopathy.
AB  - OBJECTIVE: To determine an underlying genetic defect within the differential
      diagnosis of congenital multicore myopathy. BACKGROUND: A 13.5-year-old girl
      presented with congenital-onset facial and neck weakness, slowly progressive
      severe limb girdle and axial myopathy, respiratory weakness, cardiomyopathy,
      progressive joint contractures, lumbar lordosis, progressive external
      ophthalmoplegia with ptosis, and cataracts. Muscle biopsy at 3 years revealed
      type I fiber predominance and hypotrophy, multicores with a focal decrease in
      mitochondria and oxidative enzymes, and internal nuclei. METHODS AND RESULTS:
      Serum carnitine was decreased (total, 18.2 micromol/L; free, 11.7 micromol/L).
      Urine organic acids intermittently revealed very large amounts of ethylmalonic
      and methylsuccinic acids intermittently, with elevated butyrylglycine, 2
      methylbutyrylglycine, and tiglylglycine. Fibroblast acylcarnitine profiles
      revealed marked butyrylcarnitine elevation. Electron-transferring flavoprotein
      linked reduction enzymatic assay of fibroblasts with butyryl-coenzyme A (CoA) as
      substrate, after immunoinactivation of medium-chain acyl-CoA dehydrogenase
      activity, revealed a complete absence of short-chain acyl-CoA dehydrogenase
      (SCAD) activity. No SCAD protein was detectable with Western blot analysis.
      CONCLUSIONS: This patient expands the clinical phenotype of SCAD deficiency and
      emphasizes the need for its consideration in the differential diagnosis of
      progressive external ophthalmoplegia and congenital multicore myopathy.

PMID- 9932959
TI  - GM2 gangliosidosis AB variant: clinical and biochemical studies of a Japanese
      patient.
AB  - OBJECTIVE: To determine the clinical features and biochemical basis of the first
      Japanese patient with the GM2 gangliosidosis AB variant. METHODS: The clinical
      manifestations and laboratory findings in the patient were investigated. Cultured
      fibroblasts from the patient were analyzed by means of immunofluorescence
      staining with an anti-GM2 ganglioside monoclonal antibody and thin-layer
      chromatography and immunostaining. GM1 ganglioside catabolism in cultured cells
      was analyzed by pulse labeling, and the amount of GM2 activator in cells was
      determined by Western blot analysis. Gene analysis was performed according to
      standard protocols. RESULTS: The patient showed progressive neurologic
      manifestations of quite early onset. Muscular weakness and hypotonia became
      evident by 1 month of age, and the patient then developed a startle reaction,
      severe psychomotor retardation, and myoclonic seizures. Immunocytochemical
      analysis clearly revealed the accumulation of GM2 ganglioside in cultured
      fibroblasts from the patient, and thin-layer chromatography confirmed it. Western
      blot and metabolic studies showed a complete deficiency of GM2 activator. Gene
      analysis did not reveal any mutations in the protein coding region of the GM2
      activator gene. CONCLUSION: The clinical features and biochemical basis of this
      Japanese patient with GM2 gangliosidosis AB variant were determined.
      Immunocytochemical analysis using cultured fibroblasts as samples is available
      for the diagnosis of this disease.

PMID- 9932960
TI  - A double mutation (A8296G and G8363A) in the mitochondrial DNA tRNA (Lys) gene
      associated with myoclonus epilepsy with ragged-red fibers.
AB  - OBJECTIVE: To define potential pathogenic mitochondrial DNA (mtDNA) point
      mutations in a patient with myoclonus epilepsy with ragged-red fibers (MERRF)
      syndrome. BACKGROUND: MERRF syndrome is typically associated with point mutations
      in the mtDNA tRNALys gene. METHODS: We performed morphologic, biochemical, and
      genetic analysis of muscle samples from the patient and four relatives. Molecular
      genetic studies included sequencing, PCR, and restriction enzyme analysis on
      whole muscle, blood, and single muscle fibers. RESULTS: Muscle biopsy showed
      cytochrome c oxidase (COX), negative ragged-red fibers (RRF), and a defect of
      complex I of the mitochondrial respiratory chain. We found an A8296G transition
      and a G8363A mutation in the mtDNA tRNALYs gene. The A8296G was almost
      homoplasmic in muscle and blood from the propositus and his oligosymptomatic
      maternal relatives. The G8363A mutation was heteroplasmic and more abundant in
      muscle than in blood, and its proportion correlated with clinical severity.
      Single muscle fiber analysis showed significantly higher levels of G8363A genomes
      in COX-negative than in normal fibers, and almost homoplasmic levels of mutant
      A8296G mtDNA in both COX-negative and normal fibers. The two mutations affect
      highly conserved nucleotides and were not found in controls. CONCLUSIONS: The
      G8363A mutation is pathogenic; the co-occurrence of the A8296G mutation is of
      unclear significance and is likely to be a rare polymorphism.

PMID- 9932961
TI  - Spinal muscular atrophy-like picture, cardiomyopathy, and cytochrome c oxidase
      deficiency.
AB  - The authors report a child with a spinal muscular atrophy (SMA)-like picture,
      cardiomyopathy, and cytochrome c oxidase (COX) deficiency. Electromyography and
      muscle biopsy showed findings typical of SMA. However, COX staining of the muscle
      was negative. DNA analysis did not detect deletions in the survival motor neuron
      (SMN) gene. The lactate and lactate-to-pyruvate ratios were increased in blood
      and CSF. COX activity was decreased in muscle and fibroblasts. Western blot
      analysis showed reduced contents for all COX subunits. Patients with clinical
      features resembling SMA but with an intact SMN gene should be screened for a
      mitochondrial disorder.

PMID- 9932962
TI  - Improvement of myelopathy in Sjogren's syndrome with chlorambucil and prednisone
      therapy.
AB  - The authors present a patient with Sjogren's syndrome with a fluctuating and then
      progressive myelopathic syndrome, and optic nerve involvement. Treatment with
      chlorambucil and prednisone improved the patient's function from being wheelchair
      bound to walking unaided. Spinal MRI showed multiple, extensive intraparenchymal
      areas of abnormal T2-weighted signal intensity, gadolinium enhancement, and cord
      swelling, which also improved during the period of treatment.

PMID- 9932963
TI  - Localized hypertrophic mononeuropathy involving the femoral nerve.
AB  - The authors report a case of localized hypertrophic mononeuropathy involving the
      femoral nerve in a 20-year-old woman referred because of progressive weakness and
      atrophy of the left thigh. MRI showed an enlarged femoral nerve and biopsies of
      fascicles displayed a concentric pattern of cells resembling an onion bulb. These
      cells were positive for epithelial membrane antigen immunostaining and had an
      incomplete basal lamina.

PMID- 9932964
TI  - Analysis of a very large trinucleotide repeat in a patient with juvenile
      Huntington's disease.
AB  - A patient with juvenile Huntington's disease (HD) of probable maternal
      inheritance is reported. The expanded IT-15 allele was only detected with the use
      of modified PCR and Southern transfer techniques, which showed a CAG
      trinucleotide repeat expansion of approximately 250 repeats-the largest CAG
      expansion reported within the huntingtin gene. This case emphasizes the need for
      communication between the diagnostic laboratory and the clinician to define the
      molecular genetics of unusual cases.

PMID- 9932965
TI  - Mortality cancer risk in parkinsonian patients: a population-based study.
AB  - Cancer mortality in a population-based cohort of 10,322 parkinsonian patients
      (448 deaths observed during 1987 to 1994) was compared with that of the Italian
      province of Rome using the standardized mortality ratio (SMR). The overall cancer
      mortality risk was lower in this cohort than in the reference population (SMR,
      56; 95% CI, 51 to 61). This reduction included most cancer sites as well as both
      smoking-related (SMR, 51; 95% CI, 42 to 60) and nonsmoking-related cancers (SMR,
      58; 95% CI, 52 to 65). The observed reduction in cancer mortality risk in this
      cohort cannot be explained entirely by the hypothesis that smokers are less
      likely to develop PD.

PMID- 9932967
TI  - Arterial gas embolism after decompression: correlation with right-to-left
      shunting.
AB  - Paradoxical gas embolism is a possible cause of neurologic sequelae after
      decompression in divers. The authors detected arterial bubbles after
      decompression from chamber dives in two of six divers using transcranial Doppler
      sonography (TCD). Arterial bubbles correlated with the size of right-to-left
      shunting as diagnosed by contrast TCD. The pathway of spontaneous paradoxical
      embolism was tracked for the first time, supporting the concept of paradoxical
      gas embolism as a cause of early neurologic sequelae after decompression in at
      risk divers.

PMID- 9932966
TI  - Effects of antithrombin on Binswanger's disease with antiphospholipid antibody
      syndrome.
AB  - The authors present a family with Binswanger's disease (BD) and antiphospholipid
      antibody syndrome (APAS). In one patient from this family, lupus anticoagulant
      and high levels of hemostatic markers were detected. The presence of BD and the
      clinicobiological improvements observed after antithrombin treatment in this
      patient are peculiar to this familial case of APAS.

PMID- 9932968
TI  - A lack of the R406W tau mutation in progressive supranuclear palsy and
      corticobasal degeneration.
AB  - Linkage disequilibrium studies suggest that progressive supranuclear palsy (PSP)
      is an autosomal recessive condition that maps to a polymorphism in the tau gene.
      These results provide evidence that homozygous mutations in the tau gene may
      cause PSP. Recently, a missense mutation in exon 13 of one tau allele (R406W) was
      found in a single family with an atypical clinicopathologic form of dominantly
      inherited PSP. The authors report that the R406W mutation is lacking in 25
      unrelated individuals with PSP and in six unrelated individuals with another
      tauopathy-corticobasal degeneration.

PMID- 9932969
TI  - Diffuse meningeal enhancement in patients with overdraining, long-standing
      ventricular shunts.
AB  - The authors report two elderly men with diffuse meningeal enhancement 13 and 21
      years following insertion of ventriculojugular shunts. Lumber puncture
      documenting low CSF pressures suggests that diffuse meningeal enhancement in
      patients with long-standing ventricular shunts may be secondary to dural venous
      dilatation rather than meningeal fibrosis. The authors theorize that these
      elderly patients, neither of whom had postural headache, may be less subject to
      brain "sag" because of decreased brain weight.

PMID- 9932970
TI  - Predictive value of the intracarotid amobarbital test in bihemispheric seizure
      onset.
AB  - The intracarotid amobarbital test (IAT) is used to lateralize language function
      and assess hemispheric memory. In this study 23 non-lesional epileptic patients
      were evaluated. The magnitude of the difference in IAT scores between the two
      hemispheres was significantly greater in the patients whose seizures lateralized
      on scalp or intracranial EEG than in patients with bihemispheric seizure onset.
      This suggests that the IAT is useful not only in predicting lateralized seizure
      focus, but bihemispheric onset as well.

PMID- 9932971
TI  - Bilateral cortical representation of the intrinsic lingual muscles.
AB  - Motor potentials of the intrinsic lingual muscles were recorded by surface
      electrode in a patient with left hypoglossal neuropathy. Electrical stimulation
      of the right hypoglossal nerve had contralateral lingual muscle potentials
      representing the crosstalk volume conducted electromyography signals. Magnetic
      stimulation of either cerebral hemisphere yielded motor responses on the right
      half of the tongue with more contribution from the crossed corticobulbar fibers.
      Follow-up studies showed an improvement of dysphagia and left lingual motor
      potentials.

PMID- 9932972
TI  - Bilateral optic neuropathy with IgGkappa multiple myeloma improved after
      myeloablative chemotherapy.
AB  - A 49-year-old woman with immunoglobulin GK multiple myeloma developed progressive
      visual loss with bilateral upper and lower central arcuate scotomas. Funduscopic
      and electrophysiologic studies indicated bilateral optic neuropathy. The
      immunoglobulin G fraction of the patient's serum reacted with retinal ganglionic
      cells in bovine retina. The visual abnormalities remitted after myeloablative
      chemotherapy and disappearance of the paraprotein.

PMID- 9932973
TI  - Abolished tilt suppression of the vestibulo-ocular reflex caused by a selective
      uvulo-nodular lesion.
AB  - Within the cerebellum several structures are considered to modulate the function
      of the vestibulo-ocular reflex (VOR). The nodulus and uvula have been implicated
      with the low-frequency components of the VOR, which are mediated by the velocity
      storage system. We report a patient with a selective lesion of the nodulus and
      ventral uvula. The findings suggest that nodulus and uvula normally exert an
      inhibitory effect on the velocity storage mechanism.

PMID- 9932974
TI  - Hypertrophic cranial pachymeningitis and lymphocytic hypophysitis in Sjogren's
      syndrome.
AB  - The authors describe a patient with primary Sjogren's syndrome who developed
      pachymeningitis, hypopituitarism, and central diabetes insipidus. The patient
      improved with corticosteroid pulse therapy.

PMID- 9932975
TI  - fMRI occipital activation by tactile stimulation in a blind man.

PMID- 9932976
TI  - Transient hydrocephalus as a presenting sign associated with
      adrenoleukodystrophy.

PMID- 9932977
TI  - Severe anaphylaxis with recombinant interferon beta.

PMID- 9932978
TI  - Achalasia and myasthenia gravis in a patient with thymoma.

PMID- 9932979
TI  - N-acetylcysteine therapy for Unverricht-Lundborg disease.

PMID- 9932980
TI  - Yawning in Parkinson's disease.

PMID- 9932981
TI  - Yawning in Parkinson's disease.

PMID- 9932982
TI  - Yawning in Parkinson's disease.

PMID- 9932983
TI  - The dopamine transporter gene and PD in a Chinese population.

PMID- 9932984
TI  - Rapid development of giant fusiform cerebral aneurysms in angiographically normal
      vessels.

PMID- 9932985
TI  - p-ANCA and hypertrophic pachymeningitis.

PMID- 9932986
TI  - Lack of association between human leukocyte antigens and anti-Hu syndrome in
      patients with small-cell lung cancer.

PMID- 9932987
TI  - Effectiveness of high-dose riboflavin in migraine prophylaxis.

PMID- 9932988
TI  - Gastrointestinal symptoms in syringomyelia and syringobulbia.

PMID- 9932989
TI  - Is CMTX an axonopathy?

PMID- 9932990
TI  - Lesion load reproducibility and statistical sensitivity of clinical trials in
      multiple sclerosis.

PMID- 9932991
TI  - Ofloxacin in the Lambert-Eaton myasthenic syndrome.

PMID- 9932992
TI  - Comparison of corneal wavefront aberrations after photorefractive keratectomy and
      laser in situ keratomileusis.
AB  - PURPOSE: To compare changes in the corneal wavefront aberrations after
      photorefractive keratectomy and laser in situ keratomileusis. METHODS: In a
      prospective randomized study, 22 patients with bilateral myopia received
      photorefractive keratectomy on one eye and laser in situ keratomileusis on the
      other eye. The procedure assigned to each eye and the sequence of surgery for
      each patient were randomized. Corneal topography measurements were performed
      preoperatively, 2 and 6 weeks, 3, 6, and 12 months after surgery. The data were
      used to calculate the wavefront aberrations of the cornea for both small (3-mm)
      and large (7-mm) pupils. RESULTS: Both photorefractive keratectomy and laser in
      situ keratomileusis significantly increased the total wavefront aberrations for 3
      and 7-mm pupils, and values did not return to the preoperative level throughout
      the 12-month follow-up period. For a 3-mm pupil, there was no statistically
      significant difference between photorefractive keratectomy and laser in situ
      keratomileusis at any postoperative point. For a 7-mm pupil, the post-laser in
      situ keratomileusis eyes exhibited significantly larger total aberrations than
      the post-photorefractive keratectomy eyes, where a significant intergroup
      difference was observed for spherical-like aberration, but not for coma-like
      aberration. This discrepancy seemed to be attributable to the smaller transition
      zone of the laser ablation in the laser in situ keratomileusis procedure. Before
      surgery, simulated pupillary dilation from 3 to 7 mm caused a five- to six-fold
      increase in the total aberrations. After surgery, the same dilation resulted in a
      25- to 32-fold increase in the photorefractive keratectomy group and a 28- to 46
      fold increase in the laser in situ keratomileusis group. For a 3-mm pupil, the
      proportion of coma-like aberration increased after both photorefractive
      keratectomy and laser in situ keratomileusis. For a 7-mm pupil, coma-like
      aberration was dominant before surgery, but spherical-like aberration became
      dominant postoperatively. CONCLUSIONS: Both photorefractive keratectomy and laser
      in situ keratomileusis increase the wavefront aberrations of the cornea and
      change the relative contribution of coma- and spherical-like aberrations. For a
      large pupil, laser in situ keratomileusis induces more spherical aberrations than
      photorefractive keratectomy. This finding could be attributable to the smaller
      transition zone of the laser ablation in the laser in situ keratomileusis
      procedure.

PMID- 9932993
TI  - The Advanced Glaucoma Intervention Study (AGIS): 5. Encapsulated bleb after
      initial trabeculectomy.
AB  - PURPOSE: To compare the incidence of encapsulated bleb after trabeculectomy in
      eyes with and without previous argon laser trabeculoplasty and to assess other
      risk factors for encapsulated bleb development. METHODS: After medical treatment
      failure, eyes enrolled in the Advanced Glaucoma Intervention Study (AGIS) were
      randomly assigned to sequences of interventions starting with either argon laser
      trabeculoplasty or trabeculectomy. In the present study we compared the clinical
      course for 1 year after trabeculectomy in 119 eyes with failed argon laser
      trabeculoplasty with that of 379 eyes without previous argon laser
      trabeculoplasty. Data on bleb encapsulation were collected at the time that the
      encapsulation was diagnosed, and 3 and 6 months later. RESULTS: Of multiple
      factors examined in the AGIS data for the risk of developing encapsulated bleb,
      only male gender and high school graduation without further formal education were
      statistically significant. Encapsulation occurred in 18.5% of eyes with previous
      argon laser trabeculoplasty failure and 14.5% of eyes without previous argon
      laser trabeculoplasty (unadjusted relative risk, 1.27; 95% confidence limits =
      0.81, 2.00; P = .23). After adjusting for age, gender, educational achievement,
      prescribed systemic beta-blockers, diabetes, visual field score, and years since
      glaucoma diagnosis, this difference remains statistically not significant. Four
      weeks after trabeculectomy, mean intraocular pressure was 7.5 mm Hg higher in
      eyes with (22.5 mm Hg) than without (15.0 mm Hg) encapsulated bleb; at 1 year
      after trabeculectomy and the resumption of medical therapy when needed, this
      excess was reduced to 1.4 mm Hg. CONCLUSIONS: This study, as did two previous
      studies, found male gender to be a risk factor for bleb encapsulation. Four
      studies, including the present study, have reported a higher rate of
      encapsulation in eyes with previous argon laser trabeculoplasty; in two of the
      studies, one of which was the present study, the rate was not statistically
      significantly higher; in the other two studies the rate was significantly higher.
      The 4-week postoperative mean intraocular pressure was higher in eyes with than
      without encapsulated bleb; with the resumption of medical treatment the two means
      converged after 1 year.

PMID- 9932994
TI  - Brimonidine tartrate 0.2% twice daily vs timolol 0.5% twice daily: 1-year results
      in glaucoma patients. Brimonidine Study Group.
AB  - PURPOSE: To compare the long-term efficacy and safety of brimonidine 0.2% twice
      daily with timolol 0.5% twice daily in patients with glaucoma or ocular
      hypertension. METHODS: Of the 926 patients enrolled in the study, 837 met the
      protocol entry criteria and received either brimonidine 0.2% twice daily (n =
      466) or timolol 0.5% (n = 371) twice daily in each eye for 1 year. RESULTS:
      Brimonidine and timolol significantly reduced mean intraocular pressure (P <
      .001) from baseline levels at every scheduled follow-up visit, both at hour 2
      (peak) and hour 12 (trough). At weeks 1 and 2 and months 3 and 12, significantly
      greater mean decreases in intraocular pressure (P < .040) at peak were observed
      in patients treated with brimonidine than those treated with timolol. The mean
      intraocular pressure decrease at trough was significantly greater for timolol
      than for brimonidine at each follow-up visit (P < .001). With the exception of
      ocular allergy (in 11.5% of patients using brimonidine and less than 1% using
      timolol), fewer than 3% of patients in either treatment group withdrew from the
      study prematurely as a result of a specific adverse event. Patients receiving
      timolol experienced significant decreases in heart rate (P < .001) from baseline
      at all follow-up visits. No significant changes in heart rate were seen in
      patients treated with brimonidine. Neither medication produced clinically
      significant changes in blood pressure. CONCLUSION: Brimonidine is safe and
      effective in the long-term lowering of intraocular pressure in patients with
      glaucoma or ocular hypertension, with efficacy comparable to that of timolol but
      without a notable negative chronotropic effect on the heart.

PMID- 9932995
TI  - Intermediate-term clinical experience with the Ahmed Glaucoma Valve implant.
AB  - PURPOSE: We studied the intermediate-term clinical experience with the Ahmed
      Glaucoma Valve implant (New World Medical, Inc, Rancho Cucamonga, California).
      METHODS: In this multicenter, retrospective case series, we studied 159 eyes (144
      patients) treated with the Ahmed Glaucoma Valve with a mean +/- SEM (standard
      error of mean) follow-up of 13.4 +/- 0.7 months (range, 4 to 44 months). The mean
      +/- SEM age was 60.9 +/- 1.9 years (range, 0.1 to 103 years). Surgical success
      was defined as intraocular pressure less than 22 mm Hg and greater than 5 mm Hg
      without additional glaucoma surgery and without loss of light perception.
      Postoperative use of antiglaucoma medications was not a criterion for success or
      failure. The definition of hypotony was intraocular pressure of 5 mm Hg or less
      in two consecutive visits. RESULTS: Intraocular pressure was reduced from a mean
      of 32.7 +/- 0.8 mm Hg before surgery to 15.9 +/- 0.6 mm Hg (P < .0001) at the
      most recent follow-up after surgery. The number of antiglaucoma medications was
      decreased from 2.7 +/- 0.1 before surgery to 1.1 +/- 0.1 after surgery (P <
      .0001). The cumulative probability of success was 87% at 1 year and 75% at 2
      years after surgery (Kaplan-Meier life-table analysis). Postoperatively, 24 (15%)
      of 159 eyes had intraocular pressure greater than or equal to 22 mm Hg. The
      visual acuity was improved or within one Snellen line in 131 eyes (82%).
      Complications occurred in 75 eyes (47%), the majority of which did not affect
      surgical outcome. The most common complication was obstruction of the tube, which
      was observed in 17 eyes (11%). Transient postoperative hypotony was found in 13
      eyes (8%). CONCLUSIONS: The Ahmed Glaucoma Valve implant is effective in lowering
      intraocular pressure, and postoperative hypotony is not commonly associated with
      this implant.

PMID- 9932996
TI  - The Ahmed valve in refractory pediatric glaucoma.
AB  - PURPOSE: To evaluate the efficacy of the Ahmed Glaucoma Valve implant in
      pediatric patients with refractory glaucoma. METHODS: A retrospective chart
      review was conducted of 27 eyes from 23 consecutive pediatric patients (younger
      than 18 years) with refractory glaucoma treated with Ahmed Glaucoma Valve implant
      placement. The main outcome measure was time after surgery without failure.
      Success was defined as an intraocular pressure of 21 mm Hg or less without
      visually devastating complications or additional glaucoma surgery (exclusive of
      tube revision). Previous cycloablation, which was present in a subset of eyes,
      was examined as a possible influence on postoperative intraocular pressure
      control, glaucoma medication dependence, and surgical success. RESULTS: The
      median patient age was 4.8 years (range, 0.3 to 16.8 years), with a follow-up of
      3 to 31 months (mean, 12.6 +/- 8.2 months). Intraocular pressure was reduced from
      a preoperative mean of 32.8 +/- 7.5 mm Hg to 16.7 +/- 5.4 mm Hg at 18 months
      postoperatively, with an overall success rate of 85.2% at last follow-up.
      Cumulative probabilities of success by Kaplan-Meier analysis were 90.6% at 12
      months and 58.3% at 24 months. Compared with those that did not undergo previous
      cycloablation, eyes that had undergone previous cycloablation had a lower mean
      postoperative intraocular pressure at 3- and 6-month follow-up (P < .001 and P =
      .057, respectively) and required fewer glaucoma medications at postoperative
      examination time points up to 18 months (P < or = .01 at each time point).
      Fifteen eyes (56%) required glaucoma medications after surgery. The most common
      complication was corneal-tube contact, which occurred in five eyes (18.5%). One
      eye with a wound leak required anterior chamber reformation. Retinal detachment
      occurred in one aphakic eye 2 years postoperatively, resulting in loss of vision.
      One eye with neovascular glaucoma required enucleation after an enlarging
      (presumably preexisting) medulloepithelioma was discovered. CONCLUSIONS: Ahmed
      Glaucoma Valve implantation is a useful therapy for the treatment of refractory
      pediatric glaucoma, and it may be safely used in a subgroup of eyes with
      uncontrolled intraocular pressure despite previous cycloablation procedures.

PMID- 9932997
TI  - Ultrasound biomicroscopic quantitative analysis of light-dark changes associated
      with pupillary block.
AB  - PURPOSE: To quantitatively analyze the changes in anterior chamber angle and iris
      configuration induced by varying illumination in patients with narrow angles and
      pupillary block. METHODS: Twenty-four eyes of 24 patients with pupillary block
      (mean age, 52.5 years) had ultrasound biomicroscopic images of the angle and iris
      structures obtained superiorly, nasally, inferiorly, and temporally. Images were
      performed in the light and the dark. We measured the angle opening distance, iris
      thickness, iris chord length, iris-lens touch, and iris curvature. RESULTS:
      Changes in iris and angle configuration occurred within a few seconds of a change
      in lighting. The mean dark measurements were statistically significantly less
      than the mean light measurements for angle opening distance (96 +/- 18 vs 185 +/-
      26 microm, P = .0001), iris chord length (2,505 +/- 61 vs 3,001 +/- 69 microm, P
      = .0001), and iris-lens touch (350 +/- 20 vs 693 +/- 35 microm, P = .0001). The
      mean dark measurements were statistically significantly greater than the mean
      light measurements for iris thickness at 500 microm from the scleral spur (367 +/
      10 vs 307 +/- 25 microm, P = .0001), and 1,500 microm from the scleral spur (404
      +/- 14 vs 347 +/- 12 microm, P = .0001). Iris curvature in all four quadrants was
      statistically significantly greater in the dark than the light. CONCLUSIONS: This
      study quantitatively confirms that angle narrowing in the dark in eyes with
      pupillary block is associated with iris shortening, increased iris thickness, and
      increased iris convexity. Iris-lens touch is relatively small in pupillary block
      and decreases with dilation. Angle narrowing with dilation is not related to
      increased iris-lens touch and occurs promptly without requiring time for aqueous
      pressure buildup behind the iris.

PMID- 9932998
TI  - Ultrasound biomicroscopy of ciliary body cysts.
AB  - PURPOSE: To report the incidence and sector distribution of ciliary body cysts in
      normal subjects and to assess association with age using ultrasound
      biomicroscopy. METHODS: We prospectively examined 232 eyes of 116 normal subjects
      (51 men and 65 women) ranging in age from 15 to 84 years (mean +/- SD, 45.2 +/-
      20.1). Complete ophthalmic examination, including gonioscopy and ophthalmoscopy
      with mydriasis, was performed. In addition, the circumference of the ciliary body
      was divided into eight sectors, and scanned in transverse and radial sections by
      high-resolution ultrasound biomicroscope to determine the incidence,
      distribution, and location of cysts. RESULTS: Based on one randomly chosen eye
      from each subject, cysts were detected in 63 (54.3%) of the 116 subjects. Cysts
      were found most frequently and in greater numbers in the inferior and temporal
      sectors. The incidence and the distribution range, expressed as the number of
      involved sectors per eye, were 73.1% and 3.8, respectively, for subjects 20
      approximately 29 years old; both incidence and the number of involved sectors
      decreased with age (P = .0001). Cyst diameter ranged from 200 to 2500 microm;
      mean size decreased with age (P = .001). Gender and refractive error did not
      affect the incidence and distribution. There was significant bilateral
      correlation in the number, incidence, and distribution of ciliary body cysts.
      CONCLUSION: Ultrasound biomicroscopy disclosed a high incidence of ciliary body
      cysts in normal subjects, which decreased with age. Cysts were multiple and
      bilateral in many subjects.

PMID- 9932999
TI  - Treatment outcome in fellow eyes after laser photocoagulation for retinopathy of
      prematurity.
AB  - PURPOSE: To determine the concordance in structural outcome between fellow eyes
      in patients undergoing diode laser peripheral retinal photocoagulation for
      threshold retinopathy of prematurity. METHODS: Records from 103 patients
      undergoing bilateral diode laser peripheral retinal photocoagulation for
      retinopathy of prematurity at three academic medical centers were reviewed.
      Information regarding infant gestational ages, birth weights, characteristics of
      retinopathy of prematurity, laser treatment variables, complications, and
      structural outcomes were obtained. The data were analyzed to determine the rate
      of successful structural outcomes among all eyes as well as the interocular
      outcome concordance. RESULTS: A successful structural outcome was observed in 182
      (88%) of the 206 eyes. Eighty-eight patients (85.4%) had bilateral favorable
      outcomes. Nine patients (8.7%) had bilateral unfavorable outcomes, and six
      patients (5.8%) had one favorable and one unfavorable eye. The outcome was
      concordant between fellow eyes in 94.2% of patients. This rate was higher than
      predicted if fellow-eye outcomes were truly independent (P < .00001) and did not
      depend on study center, laser settings, or location of the retinopathy of
      prematurity. Serious complications related to treatment were uncommon.
      CONCLUSIONS: Diode laser peripheral retinal photocoagulation is a safe and
      effective procedure for treating threshold retinopathy of prematurity. The
      concordance of structural outcomes between fellow eyes is higher than expected by
      chance and suggests that patient-specific factors play a key role in treatment
      response.

PMID- 9933000
TI  - Prevention of visual field defect after macular hole surgery by passing air used
      for fluid-air exchange through water.
AB  - PURPOSE: To evaluate the effect on peripheral visual field defects occurring
      after macular hole surgery of passing air that is used for fluid-air exchange
      through water before infusion to the eye. METHODS: We used Goldmann perimetry to
      measure the visual fields of patients who underwent vitrectomy to manage
      idiopathic full-thickness macular holes using either room air or humidified air
      for fluid-air exchange. We retrospectively studied visual fields measured in 39
      patients (group 1) who underwent vitrectomy without humidification of air and
      prospectively studied visual fields measured in 33 patients (group 2) who
      consecutively underwent vitrectomy with humidified air for fluid-air exchange.
      RESULTS: In group 1, nine patients (23%) had peripheral visual field defects,
      most often located in the inferior or inferotemporal quadrant. No patients (0%)
      in group 2 had a visual field defect after vitrectomy. The difference between
      groups 1 and 2 in the proportion of patients with visual field defects after
      vitrectomy was statistically significant (P = .003). CONCLUSIONS: Passing air
      used for fluid-air exchange through water seems to prevent visual field defects
      after vitrectomy for macular hole surgery. Visual field defects that occur after
      room air is used may result from desiccation of the retina by room air.

PMID- 9933001
TI  - Tarsal margin rotation with posterior lamella superadvancement for the management
      of cicatricial entropion of the upper eyelid.
AB  - PURPOSE: To report the efficacy of tarsal margin rotation with posterior lamella
      superadvancement in the management of cicatricial entropion of the upper eyelid.
      METHODS: In 15 consecutive patients, 22 eyelids with cicatricial entropion were
      managed with tarsal margin rotation and posterior lamella superadvancement. In a
      retrospective study, the technique and results were evaluated. RESULTS: In all 22
      upper eyelids, the normal eyelashes rotated away from the surface of the eye.
      Mean follow-up was 12.9 +/- 12.4 months (range, 1 to 48 months). One eyelid
      developed buckling of the tarsus. Three eyelids needed electrolysis to treat
      isolated metaplastic cilia posterior to the normal lash line. CONCLUSIONS: Tarsal
      margin rotation with posterior lamella superadvancement appears to be effective
      in managing cicatricial entropion of the upper lid.

PMID- 9933002
TI  - Clinical trials in the past 25 years and clinical research in the next 25 years.

PMID- 9933003
TI  - The role of computer assistive technology in rehabilitation of the visually
      impaired: a personal perspective.

PMID- 9933004
TI  - Disinfection of tonometers and contact lenses in the office setting: are current
      techniques adequate?
AB  - PURPOSE: To determine whether routine office techniques used to disinfect
      tonometer prisms and trial contact lenses are sufficient to prevent transmission
      of ocular infections. METHOD: We reviewed the current literature on the efficacy
      of certain disinfection protocols against commonly encountered viral, bacterial,
      and fungal pathogens as well as Acanthamoeba. RESULTS: Some commonly used
      disinfecting solutions and techniques may be inadequate for disinfection of
      viruses such as hepatitis C virus and organisms such as Acanthamoeba. When used
      in accordance with guidelines published by the United States Centers for Disease
      Control and Prevention (CDC) and the American Academy of Ophthalmology (AAO), 3%
      hydrogen peroxide is a very effective disinfectant against a wide variety of
      microorganisms. Specifically, tonometer prisms disinfected by a 5-minute soak in
      3% hydrogen peroxide (or 70% isopropyl alcohol or a 1:10 dilution of sodium
      hypochlorite) are adequately disinfected against most ocular pathogens, with the
      exception of Acanthamoeba. Trial contact lenses that are disinfected with a 2
      hour soak in 3% hydrogen peroxide are effectively rid of all pathogens of
      concern. After disinfection, rigid lenses should be stored dry, and soft lenses
      should be stored in a sterile, preserved solution. Repeat disinfection should be
      routinely performed at 1-month intervals to prevent regrowth of organisms.
      CONCLUSION: A safe office environment can be maintained by following current CDC
      recommendations for disinfection, as well as instituting some additional
      procedures.

PMID- 9933005
TI  - Corneal iron deposits after laser in situ keratomileusis.
AB  - PURPOSE: To report the occurrence and features of corneal iron line deposition
      after laser in situ keratomileusis (LASIK). METHODS: We evaluated 83 eyes
      undergoing LASIK. Corneal iron line deposition was analyzed with respect to
      preoperative spherical equivalent, attempted correction, and postoperative time
      interval. RESULTS: Thirty-five (42.2%) of 83 eyes displayed a distinctive brown
      colored corneal iron line of variable density in a ring or patch configuration
      near the margin of the ablated zone in the overlying corneal flap epithelium. The
      appearance of this iron line correlated positively with time after surgery (>3
      months) and preoperative spherical equivalent (>-4.5 diopters). CONCLUSIONS:
      Corneal iron line deposition in a ring or patch can be associated with previous
      LASIK surgery. This iron deposition within the margin of the ablated zone may
      offer insights into the dynamics of epithelial cell hyperplasia as well as basal
      cell proliferation, differentiation, and migration after LASIK.

PMID- 9933006
TI  - Posterior polymorphous dystrophy associated with posterior amyloid degeneration
      of the cornea.
AB  - PURPOSE: To describe a case of posterior polymorphous dystrophy associated with
      posterior amyloid degeneration of the cornea confirmed histopathologically and
      immunohistochemically. METHODS: An 80-year-old woman with corneal opacities
      required penetrating keratoplasty. The keratectomy specimen was evaluated by
      light microscopy and immunohistochemistry. RESULTS: Microscopic examination of
      the keratectomy specimen showed scattered fusiform deposits located in the deep
      corneal stroma. Congo red stains of the fusiform deposits confirmed the diagnosis
      of amyloidosis. Immunohistochemical stains for cytokeratin (AE1/AE3) showed that
      the endothelial cells were immunoreactive, confirming the diagnosis of posterior
      polymorphous dystrophy. CONCLUSIONS: To our knowledge, the association between
      posterior polymorphous dystrophy and posterior amyloid degeneration has not been
      reported previously.

PMID- 9933007
TI  - Technique for repair of Descemet membrane detachment.
AB  - PURPOSE: To demonstrate a successful repair of an intractable Descemet membrane
      detachment. METHODS: Case report. We used transcorneal mattress sutures to fixate
      Descemet membrane to the cornea in combination with intracameral air injection.
      RESULT: This technique resulted in reattachment of Descemet membrane and a
      substantial visual acuity improvement after complete resolution of corneal edema.
      CONCLUSIONS: Surgical repair may be needed in cases of large Descemet membrane
      detachment. This technique provides an additional surgical alternative to repair
      intractable Descemet membrane detachment without causing excessive anterior
      chamber disruption; it may also prevent the need for a penetrating keratoplasty.

PMID- 9933008
TI  - Latex allergy associated with the latex cover on the TonoPen.
AB  - PURPOSE: To describe signs and symptoms of latex allergy associated with the use
      of the TonoPen (Mentor, Norwell, Massachusetts) in a patient with severe latex
      allergy. METHODS: Case report. In a 13-year-old girl with a history of severe
      latex allergy, intraocular pressure was obtained with a TonoPen. RESULTS: TonoPen
      covers that contained latex induced agitation, bilateral conjunctival injection,
      eyelid erythema, and eyelid edema in this latex-allergic patient. Use of a
      fingertip from a sterile nonlatex glove provided accurate intraocular pressure
      measurements with the tono-pen, without a local or systemic reaction. CONCLUSION:
      In patients with latex allergies, TonoPen covers that contain latex may induce a
      substantial local and systemic reaction.

PMID- 9933009
TI  - Iris cyst associated with topical administration of latanoprost.
AB  - PURPOSE: To report an adverse side effect associated with topical latanoprost
      usage. METHOD: Case report. A 76-year-old woman with primary open-angle glaucoma
      developed an iris cyst 5 weeks after beginning treatment with latanoprost.
      Clinical examinations and slit-lamp photographs were performed. RESULTS:
      Latanoprost was discontinued. Periodic examinations disclosed that the iris cyst
      gradually diminished and finally disappeared within 3 weeks. CONCLUSION: The
      formation of an iris cyst is a possible complication of topical latanoprost
      therapy.

PMID- 9933010
TI  - Bilateral acute retinal necrosis caused by cytomegalovirus in an
      immunocompromised patient.
AB  - PURPOSE: To report a case of bilateral acute retinal necrosis caused by
      cytomegalovirus. METHODS: A diagnostic vitrectomy was performed on a patient with
      non-Hodgkin lymphoma who presented with a bilateral, rapidly progressing
      necrotizing retinitis and uveitis. RESULTS: Immunohistochemical studies and
      polymerase chain reaction disclosed cytomegalovirus as the cause of retinitis.
      The patient was treated with intravitreal and intravenous ganciclovir.
      CONCLUSIONS: Although rare, cytomegalovirus may lead to an appearance identical
      to acute retinal necrosis and should be considered among the viral etiologies of
      this syndrome.

PMID- 9933011
TI  - Laser pointer-induced macular injury.
AB  - PURPOSE: To report a patient with a macular injury caused by a laser pointing
      device. METHODS: Case report. A healthy 34-year-old man was examined 2 days after
      he deliberately gazed into the beam of a laser-pointing device with his left eye
      for an estimated 30 to 60 seconds. His uncorrected visual acuity in each eye was
      20/20. He reported a transient central scotoma in the left eye and headache after
      laser exposure. RESULTS: Both eyes were unremarkable except for a focal retinal
      pigment epithelial disturbance at the nasal edge of the fovea in the left eye.
      Fundus fluorescein angiography demonstrated window- defect type hyperfluoresence
      in the same location. CONCLUSIONS: Laser-pointing devices may cause macular
      injury when used inappropriately. Conformance with consumer safety
      recommendations should minimize potential hazards.

PMID- 9933012
TI  - Idiopathic giant retinal tears in identical twins.
AB  - PURPOSE: To report idiopathic unilateral giant retinal tears with retinal
      detachment in identical twins that occurred 2 weeks apart. METHODS: Case reports.
      RESULTS: In both patients, giant retinal tear and retinal detachment was treated
      with pars plana vitrectomy, placement of encircling scleral buckle, fluid
      perfluorocarbon exchange, endolaser treatment, perfluorocarbon-air exchange, and
      16% perfluoropropane injection. One year after retinal detachment surgery,
      cataract developed in both postoperative eyes. Phacoemulsification with posterior
      chamber intraocular lens implantation was performed on both eyes. Three and a
      half years after retinal surgery, corrected visual acuity in both treated eyes
      was 20/20, and retinal reattachment was successful. CONCLUSIONS: To our
      knowledge, this is the first report of idiopathic giant retinal tears in
      identical twins and raises the issue of genetic influences in the pathogenesis of
      this disease.

PMID- 9933013
TI  - Multiple cranial arteriovenous malformations in a child with eventual blindness
      in the affected eye.
AB  - PURPOSE: To report a case of multiple cranial arteriovenous malformations
      involving the orbit and retina. METHOD: Case report. We treated a 7-year-old girl
      who was diagnosed with a left submaxillary, a left retinal, a left orbital, and a
      middle subdural arteriovenous malformation. RESULTS: Enlargement of the
      arteriovenous malformations, except for the retinal arteriovenous malformation,
      was observed. After external carotid artery embolizations and radiation therapy
      for uncontrolled oral cavity bleeding, loss of light perception in the affected
      eye occurred, but no marked changes occurred in the retinal arteriovenous
      malformation. CONCLUSION: This rare case suggests that the clinical finding of a
      stable retinal arteriovenous malformation may be associated with enlargement of
      arteriovenous malformation lesions at other sites.

PMID- 9933014
TI  - Peripheral retinal nonperfusion associated with essential thrombocytosis.
AB  - PURPOSE: To describe a patient with retinal complications of essential
      thrombocytosis. METHOD: Case report. A 24-year-old man with acute vitreous
      hemorrhage of the right eye underwent ocular and systemic examinations to
      elucidate the origin of this condition. RESULTS: Fluorescein angiography of the
      right eye showed an avascular peripheral retina with marked capillary
      nonperfusion, arteriovenous anastomosis, and sea fan neovascularization. Blood
      studies showed thrombocytosis without other associated systemic diseases. The
      peripheral retinal capillary nonperfusion and sea fan neovascularization were
      treated with dye-laser photocoagulation, and aspirin, 80 mg daily, was given for
      systemic treatment. CONCLUSIONS: In our patient, the avascular retina was
      associated with essential thrombocytosis, which may cause an avascular peripheral
      retina with neovascularization and vitreous hemorrhage in otherwise healthy
      persons.

PMID- 9933015
TI  - Bilateral ocular ischemic syndrome secondary to giant cell arteritis progressing
      despite corticosteroid treatment.
AB  - PURPOSE: To report the development of a bilateral ocular ischemic syndrome
      despite corticosteroid treatment in a patient with giant cell arteritis. METHOD:
      Case report. RESULTS: Despite receiving high-dose intravenous methylprednisolone
      and oral prednisone for biopsy-proven giant cell arteritis that presented as a
      severe anterior ischemic optic neuropathy in the right eye, a patient developed
      progressive ocular ischemia in that eye as well as an ocular ischemic syndrome in
      the fellow eye. CONCLUSIONS: Some patients with giant cell arteritis, possibly
      patients with other underlying systemic vasculopathies, are refractory to what
      should be adequate treatment with systemic corticosteroids and may develop a
      bilateral ocular ischemic syndrome.

PMID- 9933016
TI  - Anterior ischemic optic neuropathy following the use of a nasal decongestant.
AB  - PURPOSE: To report a case of sequential anterior ischemic optic neuropathy
      temporally related to the sequential use of a decongestant nasal spray. METHODS:
      A 43-year-old woman was evaluated for sequential bilateral vision loss following
      the use of oxymetazoline nasal spray. RESULTS: Thorough investigation of possible
      etiologies causing the bilateral anterior ischemic optic neuropathy was negative.
      Our patient had several predisposing risk factors for ischemic optic neuropathy,
      including diabetes mellitus, hypertension, and crowded optic nerve heads. Before
      each acute optic neuropathy, the patient used two to three puffs of oxymetazoline
      nasal spray. CONCLUSION: Decongestants have been associated with ischemic and
      hemorrhagic vascular events. Vasoconstriction secondary to oxymetazoline use may
      precipitate anterior ischemic optic neuropathy.

PMID- 9933017
TI  - Abnormal collagen fibrils in nanophthalmos: a clinical and histologic study.
AB  - PURPOSE: To report the successful treatment of choroidal detachment in a patient
      with nanophthalmos and to report histopathologic findings in this patient's
      sclera. METHODS: Choroidal detachment, secondary angle closure, and nanophthalmos
      were diagnosed using biomicroscopy, indirect ophthalmoscopy, and echography. Full
      thickness sclerectomies in four quadrants were made on the right eye. Sclerae
      from these sclerectomies were studied ultrastructurally. RESULTS: Best-corrected
      visual acuity improved to RE, 20/60 from 20/100 preoperatively; the anterior
      chamber deepened, and the choroidal detachment resolved. Histopathologic studies
      of each of the three scleral layers disclosed abnormal collagen fibrils that were
      frayed, split, and contained lightly stained cores. CONCLUSION: New findings
      include the identification of collagen with lightly stained centers and
      identification of differences in collagen morphology in different areas of the
      sclera in a nanophthalmic eye.

PMID- 9933018
TI  - Small retinal hemorrhages as the only signs of an intracranial aneurysm.

PMID- 9933019
TI  - The Madurai Intraocular Lens Study I-III.

PMID- 9933020
TI  - Protein phosphatase 2A: who shall regulate the regulator?
AB  - Protein phosphatases are responsible for keeping the signaling output of stimulus
      activated protein kinases in check; but protein phosphatases are also themselves
      targets and conveyors of biological signals. Among the major serine/threonine
      phosphatases, protein phosphatase 2A (PP2A) appears to play a privileged role in
      the regulation of cell growth and division. How PP2A is regulated is an
      intriguing question. This review will focus on the role of local protein-protein
      interactions in PP2A control. Work from a number of laboratories has shown that
      the catalytic activity, substrate specificity, and subcellular targeting of PP2A
      are regulated by a remarkably diverse range of regulatory subunits and enzyme
      inhibitors. On the pathological side, DNA tumor viruses subvert PP2A function by
      producing proteins that compete with specific regulatory subunits. By interfering
      with PP2A, these viral proteins can elicit changes in the activity of specific
      signal transduction pathways, such as the mitogen-activated protein kinase
      cascade. Recent data indicate that besides classical holoenzyme forms, a fraction
      of PP2A molecules are associated with novel partners implicated in signal
      transduction. PP2A biochemically and genetically interacts with the Tap42/alpha4
      protein, which is part of a rapamycin-sensitive pathway that connects
      extracellular stimuli to the initiation of mRNA translation. PP2A also binds to
      CK2alpha, the catalytic subunit of CK2 (formerly casein kinase 2), and binding is
      sensitive to mitogenic signaling. The potent effect of quantitatively minor PP2A
      partners might be explained by a general requirement for docking interactions
      with substrates under intracellular conditions.

PMID- 9933021
TI  - The importance of being dehydroepiandrosterone sulfate (in the blood of
      primates): a longer and healthier life?
AB  - The general aging sequence in tissues of healthy human beings is proposed to be:
      capillary endothelial cell damage --> arteriosclerosis --> decreased blood flow -
      > metabolic dysregulation --> secondary tissue damage. Molecular O2 is an
      obligatory substrate for the successive syntheses of 17alpha-OH pregnenolone and
      dehydroepiandrosterone (DHEA) by cytochrome P450c17 in the zona reticularis of
      the adrenal cortex, in which it is suggested that arteriosclerosis --> decreased
      blood flow --> O2 and glucose deficit --> decreased O2-requiring synthesis of
      DHEA --> eventual decrease in number of DHEA-synthesizing cells. Aging changes in
      the zona reticularis synergize with those in the hypothalamo-hypophyseal
      machinery that controls it neurally and hormonally, with ACTH-evoked pulsatile
      floods of cortisol coming from the adrenal zona fasciculata, with the onslaught
      of free radicals generated by the metabolism of catecholamines released from
      interdigitating cells of the adrenal medulla, and with age-correlated
      disabilities of erythrocytes to bind and release O2 to decrease the viability of
      the DHEA and dehydroepiandrosterone sulfate (DHEAS)-forming cells. One of the
      chief functions of serum DHEAS in the male may be to act as an allosteric
      facilitator of the binding of testosterone (T) to serum albumin, thereby helping
      target T to specific receptors and to allosteric sites for rapid and efficient
      action at the cellular level. There is reason to consider combining O2 therapy
      with appropriate administration of DHEA and T to optimize steroid functionality
      in the healthy aging male, and thus, possibly, to alleviate some of the age
      related cognitive and physical decrements that occur.

PMID- 9933022
TI  - Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA
      expression by pharmacological agents in human ovarian carcinoma cells.
AB  - Excision repair cross complementation group 1 (ERCC-1) is a DNA repair gene that
      is essential for life, and it appears to be a marker gene for nucleotide excision
      repair activity. Overexpression of ERCC-1 during cisplatin-based chemotherapy is
      associated with clinical and cellular drug resistance. We therefore began to
      assess the influence of various pharmacological agents on the induction of ERCC-1
      mRNA in A2780/CP70 human ovarian carcinoma cells. Cisplatin exposure in culture
      resulted in a 4- to 6-fold induction for the steady-state level of ERCC-1 mRNA in
      A2780/CP70 cells. ERCC-1 mRNA induction was concentration and time dependent.
      Cyclosporin A and herbimycin A, which suppress c-fos and c-jun gene expressions,
      respectively, blocked the cisplatin-induced increase in ERCC-1 mRNA. This effect
      of cyclosporin A or herbimycin A on the down-regulation of ERCC-1 correlates with
      enhanced cytotoxicity of cisplatin in this system. The products of c-fos and c
      jun are components of the transcription factor AP-1 (activator protein 1). 12-O
      Tetradecanoylphorbol 13-acetate (TPA), a known AP-1 agonist, induced ERCC-1 mRNA
      to the same extent as cisplatin, but did not synergize with cisplatin in this
      regard. The TPA effect was biphasic, with an initial increase during the first 1
      6 hr, followed by decreasing mRNA levels at 24-72 hr. These data suggest that the
      effects of these pharmacological agents on ERCC-1 gene expression may be mediated
      through the modulation of AP-1 activities.

PMID- 9933023
TI  - Involvement of P1 receptors in the effect of forskolin on cyclic AMP accumulation
      and export in PC12 cells.
AB  - In PC12 cells, forskolin as well as the adenosine receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA) increased intracellular adenosine-3',5'-cyclic
      monophosphate (cyclic AMP) levels, which peaked at 45-60 minutes and declined
      thereafter. Maximum levels were 3000 and 1700 pmol/10(6) cells during treatment
      with 10 microM forskolin or 0.1 microM NECA, respectively. Extracellular cyclic
      AMP rose with time, at mean rates of 24.7 (forskolin) and 11.3 (NECA)
      pmol/min/10(6) cells. With either drug, a linear correlation was obtained between
      the calculated time integral of intracellular cyclic AMP and the measured
      extracellular cyclic AMP levels, indicating that the outflow of cyclic AMP was
      sustained by a nonsaturated transport system. The ability of forskolin to
      increase intracellular and extracellular cyclic AMP levels was hindered in a
      concentration-dependent manner by 8-(p-sulfophenyl)theophylline (8-SPT). A
      similar inhibition was exerted by other two adenosine receptor antagonists, 8
      cyclopentyl-1,3-dipropylxanthine and 3,7-dimethyl-1-propargylxanthine. The
      concentration-response curve to adenosine was shifted to the right by 25 microM 8
      SPT, whereas that of forskolin was shifted downwards. Adenosine deaminase (ADA,
      EC 3.5.44, 1 U/mL) reduced the intracellular cyclic AMP response to forskolin by
      68%, whereas the adenosine transport inhibitor, dipyridamole (10 microM),
      significantly increased 1 and 10 microM forskolin-dependent cyclic AMP
      accumulation. Erythro-9-(2-hydroxy-3-nonyl)adenine (10 microM), an inhibitor of
      ADA, and alpha,beta-methyleneadenosine 5'-diphosphate (100 microM), an inhibitor
      of ecto-5'-nucleotidase, did not alter forskolin activity. These results
      demonstrate that a cyclic AMP extrusion system operates in PC12 cells during
      adenylyl cyclase stimulation by forskolin and that this stimulation involves a
      synergistic interaction with endogenous adenosine. However, extruded cyclic AMP
      does not appear to significantly contribute to the formation of the endogenous
      adenosine pool.

PMID- 9933024
TI  - Inhibition of human smooth muscle cell proliferation in culture by farnesyl
      pyrophosphate analogues, inhibitors of in vitro protein: farnesyl transferase.
AB  - In this study, it was investigated whether and how inhibitors of protein:farnesyl
      transferase (PFT) can inhibit the proliferation of human smooth muscle cells
      (HSMC) in culture. Several farnesyl pyrophosphate (FPP) analogues were
      synthesized and tested in vitro for their specificity in inhibiting squalene
      synthase (SS), PFT, or protein:geranylgeranyl transferase-1 (PGGT-1) activities
      (the latter was determined using a newly designed assay). One of these compounds
      appeared to be a strong PFT inhibitor (IC50 value: 340 nM) and a weak inhibitor
      in the other two enzyme assays. This compound (designated as TR006) inhibited the
      farnesylation of Ras in a Ha-ras transfected cell line (Cohen et al., Biochem.
      Phamacol. 49: 839-845, 1995) and concomitantly slowed down the growth of these
      cells. Twenty-five microM of TR006 inhibited the proliferation of HSMC isolated
      from left internal mammary artery, as measured by counting the cells over a
      period of three cell cycles (10 days). A structurally related compound (TR007), a
      specific SS inhibitor, did not influence HSMC proliferation under the same
      conditions. The inhibition by TR006 was concentration-dependent. In HSMC,
      synchronized by serum depletion, platelet-derived growth factor (PDGF) or basic
      fibroblast growth factor (bFGF)-induced DNA synthesis was decreased by a 29-hr
      pretreatment with 100 microM of TR006, indicating that this inhibitor acted in an
      early phase of the cell cycle, probably by preventing protein isoprenylation.
      Some other FPP analogues with comparable IC50 values in the in vitro PFT assay
      were also able to decrease bFGF-induced DNA synthesis without affecting cell
      viability. A more negatively charged member of this group, TR018, did not
      influence the growth factor-induced DNA synthesis, probably due to an impaired
      uptake into the cells. However, the pivaloyloxomethyl derivative of this
      compound, which is uncharged, and is thought to be converted into TR018 within
      the cells, showed a strong decrease in bFGF-induced DNA synthesis in HSMC. These
      data suggest that the compounds investigated may be developed further for
      treatment of conditions in which undesirable proliferation of smooth muscle cells
      plays an important role.

PMID- 9933025
TI  - Peroxidase-catalyzed effects of indole-3-acetic acid and analogues on lipid
      membranes, DNA, and mammalian cells in vitro.
AB  - This study aimed to explore the mechanisms and molecular parameters which control
      the cytotoxicity of derivatives of indole-3-acetic acid (IAA) when oxidatively
      activated by horseradish peroxidase (HRP). Lipid peroxidation was measured in
      liposomes, damage to supercoiled plasmid DNA assessed by gel electrophoresis,
      free radical intermediates detected by EPR following spin trapping, binding of
      IAA-derived products demonstrated by 3H labelling, stable products measured by
      HPLC, and cytotoxicity in hamster fibroblasts measured by clonogenic survival.
      IAA, and nine analogues more easily oxidized by HRP, caused lipid peroxidation in
      liposomes, but not detectably in membranes of hamster fibroblasts, and were
      cytotoxic after HRP activation to varying degrees. Cytotoxicity was not
      correlated with activation rate. The hydrophilic vitamin E analogue, Trolox,
      inhibited cytotoxicity, whereas loading fibroblasts with vitamin E was
      ineffective, consistent with an oxidative mechanism in which radical precursors
      to damage are intercepted by Trolox in the aqueous phase. However, two known
      oxidation products were nontoxic (the 3-carbinol and 3-aldehyde, both probably
      produced from 3-CH2OO* peroxyl radicals via the 3-CH*2 [skatolyl] radical
      following decarboxylation of the radical cation). The skatolyl radical from IAA
      was shown by EPR with spin trapping to react with DNA; electrophoresis showed
      binding to occur. Treatment of hamster fibroblasts with 5-3H-IAA/HRP resulted in
      intracellular bound 3H. Together with earlier results, the new data point to
      unknown electrophilic oxidation products, reactive towards intracellular targets,
      being involved in cytotoxicity of the IAA/HRP combination, rather than direct
      attack of free radicals, excited states, or membrane lipid peroxidation.

PMID- 9933027
TI  - Distinct regulation of glucose transport by interleukin-3 and oncogenes in a
      murine bone marrow-derived cell line.
AB  - Growth factors and oncogenes promote glucose uptake, but the extent to which
      increased uptake is regulated at the level of glucose transporter function has
      not been clearly established. In this paper, we show that interleukin-3 (IL-3), a
      cytokine growth factor, and the transforming oncogenes ras and abl alter the
      activation state of glucose transporters by distinct mechanisms. Using bone
      marrow-derived IL-3-dependent 32Dc13 (32D clone 3) cells and 32D cells
      transformed with ras and abl oncogenes, we demonstrated that IL-3 enhanced [3H]-2
      deoxyglucose (2-DOG) uptake in parental 32Dc13 cells by 40-50% at 0.2 mM 2-DOG,
      and this was associated with a 2.5-fold increase in transporter affinity for
      glucose (reduced Km). In comparison, ras and abl oncogenes enhanced 2-DOG uptake
      by 72-112%, associated with a 2-fold greater transporter affinity for glucose.
      The tyrosine kinase inhibitor genistein reversed the effects of both IL-3 and
      oncogenes on glucose uptake and reduced transporter affinity for glucose.
      Likewise, with exponentially growing 32D cells in the presence of IL-3, a protein
      kinase C inhibitor, staurosporine, and a phosphatidylinositol 3-kinase (PI-3)
      kinase inhibitor, wortmannin, inhibited 2-DOG uptake and decreased transporter
      affinity for glucose. In contrast, in oncogene-transformed cells, staurosporine
      inhibited 2-DOG uptake but failed to decrease transporter affinity for glucose,
      whereas wortmannin did not affect 2-DOG uptake. Inhibition of protein tyrosine
      phosphatases with vanadate enhanced 2-DOG uptake and transporter affinity for
      glucose in parental cells and in ras-transformed cells but had little effect on
      abl-transformed cells. Consistently, the serine/threonine phosphatase type 2A
      inhibitor okadaic acid enhanced 2-DOG uptake and transporter affinity for glucose
      in parental cells but had little effect on ras- or abl-transformed cells. These
      results demonstrate differences in the regulation of glucose transport in
      parental and oncogene-transformed 32D cells. Thus, IL-3 responses are dependent
      upon tyrosine, serine/threonine, and PI-3 kinases, whereas ras and abl effects on
      glucose transport depend upon tyrosine phosphorylation but are compromised in
      their dependence upon serine/threonine and PI-3 kinases.

PMID- 9933026
TI  - The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX
      1) on human vascular smooth muscle cells and monocytes and its down-regulation by
      lovastatin.
AB  - Accumulation of oxidatively modified low-density lipoprotein (oxLDL) in the
      vascular wall is a characteristic feature of atherosclerosis. oxLDL can be taken
      up into monocytes, smooth muscle cells, and endothelial cells by several known
      scavenger receptors such as scavenger receptor class A I and II, CD36, and CD68.
      A new lectin-like oxLDL receptor (LOX-1) was recently found in bovine and human
      endothelial cells. We studied whether LOX-1 is also expressed in other cells
      present in the atherosclerotic lesion and whether its expression can be modified.
      We found LOX-1 expression in human blood monocytes, umbilical smooth muscle and
      endothelial cells, and 3T3 fibroblasts. LOX-1 mRNA expression in monocytes could
      be significantly suppressed by lovastatin. Thus, LOX-1 expression is not
      restricted to endothelial cells and its down-regulation by HMG-CoA reductase
      inhibitors could contribute to the clinical benefits of these drugs.

PMID- 9933028
TI  - Decreased resistance to gemcitabine (2',2'-difluorodeoxycitidine) of cytosine
      arabinoside-resistant myeloblastic murine and rat leukemia cell lines: role of
      altered activity and substrate specificity of deoxycytidine kinase.
AB  - We determined the potential activity of 2',2'-difluorodeoxycytidine (gemcitabine,
      dFdC) in 1-beta-D-arabinofuranosylcytidine (ara-C)-sensitive and-resistant
      leukemia cell lines. Both drugs are phosphorylated by deoxycytidine kinase (dCK);
      the triphosphates, dFdCTP and ara-CTP, respectively, are incorporated into DNA.
      In the murine leukemia cell line L1210, induction of resistance to ara-C resulted
      in the 2200-fold resistant subline L4A6. The Brown Norway rat myelocytic leukemia
      ara-C-sensitive cell line (BCLO) was >300-fold more sensitive to ara-C than its
      variant Bara-C. In L1210 cells, gemcitabine was 8-fold more active than ara-C; in
      L4A6, BCLO, and Bara-C cells, gemcitabine was 16-, 28-, and more than 3-fold more
      active than ara-C, respectively. A partial explanation for these differences may
      be the higher dCK activity in the parental cell lines L1210 and BCLO with
      gemcitabine compared to ara-C as a substrate. DCK activity was not or hardly
      detectable in the resistant L4A6 and Bara-C cell. In the rat leukemia cell lines,
      deoxycytidine (dCyd) phosphorylation activity showed an aberrant pattern, since
      the activity with dCyd was 1.5-fold higher in the Bara-C cell line compared with
      BCLO, possibly due to thymidine kinase 2. The wild-type L1210 cells accumulated
      at least 3-fold more ara-CTP and dFdCTP than the rat leukemia cell line BCLO. The
      ara-C-resistant variants L4A6 and Bara-C did not accumulate dFdCTP or ara-CTP. In
      conclusion, gemcitabine was more active than ara-C in all leukemia cell lines
      tested. The sensitivity of the wild-type cell lines correlates with the
      accumulation of dFdCTP and ara-CTP, but is independent of dCK. However, both
      resistant variants had decreased dCK activities, but were relatively more
      sensitive to dFdC than to ara-C.

PMID- 9933029
TI  - Combination chemotherapy studies with gemcitabine and etoposide in non-small cell
      lung and ovarian cancer cell lines.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and etoposide (4'-demethylepipodo
      phyllo-toxin-9-4,6-O-ethylidene-beta-D-g lucopyranoside, VP-16) are
      antineoplastic agents with clinical activity against various types of solid
      tumors. Because of the low toxicity profile of dFdC and the differences in
      mechanisms of cytotoxicity, combinations of both drugs were studied in vitro. For
      this purpose, we used the human ovarian cancer cell line A2780, its cis-diammine
      dichloroplatinum-resistant and VP-16 cross-resistant variant ADDP, and two non
      small cell lung cancer cell lines, Lewis Lung (LL, murine) and H322 (human). The
      interaction between the drugs was determined with the multiple drug effect
      analysis (fixed molar ratio) and with a variable drug ratio. In the LL cell line,
      the combination of dFdC and VP-16 at a constant molar ratio (dFdC:VP-16 = 1:4 or
      1:0.125 after 4- or 24-hr exposure, respectively) was synergistic (combination
      index [CI], calculated at 50% growth inhibition = 0.7 and 0.8, respectively; CI
      <1 indicating synergism). After 24- and 72-hr exposure to both drugs at a
      constant ratio, additivity was found in the A2780, ADDP, and H322 cell lines
      (dFdC:VP-16 = 1:500 for both exposure times in these cell lines). When cells were
      exposed to a combination of dFdC and VP-16 for 24 or 72 hr, with VP-16 at its
      IC25 and dFdC in a concentration range, additivity was found in both the LL and
      H322 cells; synergism was observed in the A2780 and ADDP cells, which are the
      least sensitive to VP-16. Schedule dependency was found in the LL cell line; when
      cells were exposed to dFdC 4 hr prior to VP-16 (constant molar ratio, total
      exposure 24 hr), synergism was found (CI = 0.5), whereas additivity was found
      when cells were exposed to VP-16 prior to dFdC (CI = 1.6). The mechanism of
      interaction between the drugs was studied in more detail in the LL cell line;
      dFdCTP accumulation was 1.2-fold enhanced by co-incubation with VP-16, and was
      even more pronounced (1.4-fold) when cells were exposed to VP-16 prior to dFdC.
      dCTP levels were decreased by VP-16 alone as well as by the combination of both
      compounds, which may favor phosphorylation of dFdC, thereby increasing dFdCTP
      accumulation. DNA strand break (DSB) formation was increased for exposure to both
      compounds together compared to exposure to each compound separately, this effect
      being most pronounced when cells were exposed to VP-16 prior to dFdC (38% and 0%
      DSB for dFdC and VP-16 alone, respectively and 97% DSB for the combination). The
      potentiation in DSB formation might be a result of the inhibition of DNA repair
      by dFdC. Provided the right schedule is used, VP-16 is certainly a compound
      eligible for combination with dFdC.

PMID- 9933030
TI  - Enzymes of porcine brain hydrolyzing 2-arachidonoylglycerol, an endogenous ligand
      of cannabinoid receptors.
AB  - Anandamide and 2-arachidonoylglycerol (2-AG) are two endogenous ligands for the
      cannabinoid receptors, and their cannabimimetic activities are lost when they are
      hydrolyzed enzymatically. Cytosol and particulate fractions of porcine brain
      exhibited a high 2-AG hydrolyzing activity of 100 nmol/min/mg protein. Most of
      the activity could be attributed to a monoacylglycerol lipase-like enzyme that
      did not hydrolyze anandamide. It was separated by hydroxyapatite chromatography
      from anandamide amidohydrolase, which is also capable of hydrolyzing 2-AG as well
      as anandamide. Thus, porcine brain has at least two enzymes capable of
      hydrolyzing 2-AG. The 2-AG hydrolase activities of both the cytosolic and
      particulate enzymes were irreversibly and time-dependently inhibited by methyl
      arachidonyl fluorophosphonate with IC50 values as low as 2-3 nM.

PMID- 9933031
TI  - Epidermal growth factor and angiotensin II regulation of extracellular signal
      regulated protein kinase in rat liver epithelial WB cells.
AB  - Activation of extracellular signal-regulated protein kinase (ERK) is considered
      essential for mitogenesis. In the present study, rat liver epithelial WB cells
      were used to investigate the relative roles of Ca2+, protein kinase C (PKC), and
      protein tyrosine phosphorylation in mitogenesis and activation of the ERK pathway
      stimulated by epidermal growth factor (EGF) and angiotensin II (Ang II). The
      sensitivity of the ERK pathway to Ca2+ was studied by using 1,2-bis (O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) to chelate intracellular
      Ca2+ and a low extracellular Ca2+ concentration to prevent Ca2+ influx. Agonist
      induced PKC activation was diminished by inhibition of PKC by GF-109203X
      (bisindolylmaleimide) or by down-regulation of PKC by long-term treatment of the
      cells with phorbol myristate acetate (PMA). Our results show that although
      activation of PKC was critical for mitogenesis induced by Ang II or EGF, the
      initial activation of ERK by both agonists in these cells was essentially
      independent of PKC activation and was insensitive to Ca2+ mobilization. This is
      in contrast to the findings in some cell types that exhibit a marked dependency
      on mobilization of Ca2+ and/or PKC activation. On the other hand, an obligatory
      tyrosine phosphorylation step for activation of ERK was indicated by the use of
      protein tyrosine kinase inhibitors, which profoundly inhibited the activation of
      ERK by EGF, Ang II, and PMA. Additional experiments indicated that tyrosine
      phosphorylation by a cytosolic tyrosine kinase may represent a general mechanism
      for G-protein coupled receptor mediated ERK activation.

PMID- 9933032
TI  - Anti-inflammatory mechanism of alminoprofen: action on the phospholipid
      metabolism pathway.
AB  - Alminoprofen is a nonsteroidal anti-inflammatory drug (NSAID) of the
      phenylpropionic acid class. It has anti-inflammatory properties different from
      the classical NSAID. Using both in vitro systems of cells in culture and in vivo
      models of inflammation, we report here that alminoprofen possesses both
      antiphospholipase A2 (PLA2) activity and anti-cycloxygenase (COX) activity. The
      PLA2 targeted by alminoprofen is likely the secretory phospholipase A2 (sPLA2)
      while the COX targeted is the COX-2.

PMID- 9933033
TI  - Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil.
AB  - Interest in the health-promoting effects of virgin olive oil, an important part
      of the 'Mediterranean diet', prompted us to determine the anti-eicosanoid and
      antioxidant effects in leukocytes of the principal phenolic compounds from the
      'polar fraction': oleuropein, tyrosol, hydroxytyrosol, and caffeic acid. In
      intact rat peritoneal leukocytes stimulated with calcium ionophore, all four
      phenolics inhibited leukotriene B4 generation at the 5-lipoxygenase level with
      effectiveness hydroxytyrosol > oleuropein > caffeic acid > tyrosol (approximate
      EC50 values: 15, 80, 200, and 500 microM, respectively). In contrast, none of
      these compounds caused substantial inhibition of thromboxane generation via the
      cyclo-oxygenase pathway. Hydroxytyrosol, caffeic acid, oleuropein, and tyrosol
      (decreasing order of effectiveness) also quenched the chemiluminescence signal
      due to reactive oxygen species generated by phorbol myristate acetate-stimulated
      rat leukocytes. None of these compounds were toxic to leukocytes at the
      concentrations tested. We conclude that the phenolics found in virgin olive oil
      possess an array of potentially beneficial lipoxygenase-inhibitory, prostaglandin
      sparing, and antioxidant properties.

PMID- 9933034
TI  - Gemcitabine and other new chemotherapeutic agents for the treatment of metastatic
      bladder cancer.
AB  - An improved quality of life secondary to reduced chemotherapy toxicity is an
      important end point in the treatment of all patients with metastatic cancer. In
      this review, we have demonstrated that gemcitabine and gemcitabine/cisplatin
      combinations appear to have a reduced toxicity profile compared with MVAC. Phase
      II studies with gemcitabine and cisplatin have shown good response rates that are
      possibly equivalent to MVAC, and a Phase III trial is now completed. Similar data
      have been reported for the paclitaxel/carboplatin combination and a Phase III
      trial comparing that combination with MVAC is planned. For patients with TCC who
      are in mild renal failure or who have significant underlying medical conditions,
      gemcitabine can also be considered as a reasonable single agent therapy. Complete
      responses can be seen, even in patients who are older than the age of 70. Moore
      et al., for example, demonstrated near complete responses to gemcitabine
      monotherapy in 4 patients older than 80 years of age. In conclusion, chemotherapy
      options for patients with metastatic bladder cancer have changed significantly
      with the addition of gemcitabine and other drugs to the armentarium. The
      integration of gemcitabine into the initial chemotherapy plan for these patients
      is still being developed. It is clear that this agent should be included in the
      management discussions of all patients with metastatic bladder cancer.

PMID- 9933035
TI  - Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy
      transurethral microwave thermotherapy for lower urinary tract symptoms of benign
      prostatic hyperplasia: a randomized, prospective clinical trial.
AB  - OBJECTIVES: Improved long-term results with respect to symptoms, voiding
      function, and quality of life (QOL) in patients with lower urinary tract symptoms
      (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high
      energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker
      treatment alone. However, maximal improvement after TUMT is not attained until 3
      to 6 months after treatment. Measures to provide earlier symptom relief and
      improved voiding function and QOL would add to the clinical utility of TUMT. The
      objective of the present study was to determine whether neoadjuvant and adjuvant
      alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of
      patients with BPH. METHODS: In this randomized, prospective study of 81 patients
      with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4
      mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score
      (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before
      treatment and at periodic intervals thereafter up to 12 weeks after TUMT.
      RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95%
      confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were
      15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to
      17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005).
      However, by the final evaluation at 12 weeks, no significant difference between
      the groups in mean IPSS was evident. A similar temporal pattern of difference
      between the two study groups was also observed in QOL score. No significant
      between-group difference in mean Qmax was evident after TUMT. Urinary retention 1
      week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients
      compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS:
      Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater
      early symptom reduction and QOL score improvement after TUMT, adding to the
      clinical utility of this minimally invasive treatment modality. In addition, post
      TUMT complications such as urinary retention may be reduced.

PMID- 9933037
TI  - Multimedia to teach urology to medical students.
AB  - OBJECTIVES: To test the hypothesis that an interactive multimedia-based computer
      application may be used to teach urology to undergraduate medical students.
      METHODS: Third-year medical students rotating on their urology clerkship were
      studied. Student knowledge was measured with a multiple choice test administered
      in a pretest-post-test experimental design. The educational intervention was a
      multimedia-based application that presented a clinical module on hematuria, using
      natural language-like entries. Student attitudes toward the multimedia
      application were assessed by a survey. RESULTS: Twenty-three consecutive third
      year medical students participated. Mean pretest and post-test scores +/-
      standard deviation were 35%+/-11% versus 74%+/-17%, respectively, P<0.0001.
      Student questionnaire responses indicated highly positive opinions that the
      multimedia-based module was easy to use, was fun, provided natural patient
      responses, had clear exercises, provided immediate feedback, was educational, and
      had a nonthreatening format, and that the multiple choice questions were clear
      and fair. CONCLUSIONS: Multimedia-based education may be used to teach urology to
      undergraduate medical students.

PMID- 9933036
TI  - Recombinant vaccinia-PSA (PROSTVAC) can induce a prostate-specific immune
      response in androgen-modulated human prostate cancer.
AB  - OBJECTIVES: Prostate cancer recurrence, evidenced by rising prostate-specific
      antigen (PSA) levels after radical prostatectomy, is an increasingly prevalent
      clinical problem in need of new treatment options. Preclinical studies have
      suggested that for tumors in general, settings of minimal cancer volume may be
      uniquely suitable for recombinant vaccine therapy targeting tumor-associated
      antigens. A clinical study was undertaken to evaluate the safety and biologic
      effects of vaccinia-PSA (PROSTVAC) administered to subjects with
      postprostatectomy recurrence of prostate cancer and to assess the feasibility of
      interrupted androgen deprivation as a tool for modulating expression of the
      vaccine target antigen, as well as detecting vaccine bioactivity in vivo.
      METHODS: A limited Phase I clinical trial was conducted to evaluate the safety
      and biologic effects of vaccinia-PSA administered in 6 patients with androgen
      modulated recurrence of prostate cancer after radical prostatectomy. End points
      included toxicity, serum PSA rise related to serum testosterone restoration, and
      immunologic effects measured by Western blot analysis for anti-PSA antibody
      induction. RESULTS: Toxicity was minimal, and dose-limiting toxicity was not
      observed. Noteworthy variability in time required for testosterone restoration
      (after interruption of androgen deprivation therapy) was observed. One subject
      showed continued undetectable serum PSA (less than 0.2 ng/mL) for over 8 months
      after testosterone restoration, an interval longer than those reported in
      previous androgen deprivation interruption studies. Primary anti-PSA IgG antibody
      activity was induced after vaccinia-PSA immunization in 1 subject, although such
      antibodies were detectable in several subjects at baseline. CONCLUSIONS:
      Interrupted androgen deprivation may be a useful tool for modulating prostate
      cancer bioactivity in clinical trials developing novel biologic therapies. Immune
      responses against PSA may be present among some patients with prostate cancer at
      baseline and may be induced in others through vaccinia-PSA immunization.

PMID- 9933038
TI  - Use of diuretic renogram in evaluation of patients before and after
      endopyelotomy.
AB  - OBJECTIVES: Endopyelotomy is a widely accepted alternative in the treatment of
      ureteropelvic junction (UPJ) obstruction, with success rates between 63% and 88%.
      However, various methods have been used to evaluate patients with UPJ
      obstruction, making it difficult to compare results. Diuretic renography has the
      potential to unify the evaluation if performed in standard ways. In this report,
      we present a standardized protocol for diuretic renography. METHODS: Nineteen
      endopyelotomies were performed by one surgeon (E.B.K.) at our institution. The 16
      patients were evaluated with technetium 99m MAG-3 diuretic renography. The
      presence or absence of obstruction was classified according to the differential
      renal function, time activity curves, and Tmax to T 1/2max time. Three patients
      had a postoperative Whitaker's test. RESULTS: Eight patients had pre- and
      postoperative diuretic renograms at our institution. This group was stratified by
      their differential renal function. Among 4 patients with differential renal
      function greater than 35%, 3 of 4 showed progressive improvement in renal
      function postoperatively, 4 of 4 had a Tmax to T 1/2max time less than 10
      minutes, and 3 of 4 ha d unobstructed time activity curves. Five patients had
      postoperative renograms only. Of these 5 patients, 4 had differential renal
      function greater than 35% and 3 of 5 had normal-appearing curves and normal Tmax
      to T 1/2max time. Three patients required a second endopyelotomy and 2 of these
      underwent a dismembered pyeloplasty. CONCLUSIONS: Standardized diuretic
      renography should be used as an objective test for the evaluation of patients
      with UPJ obstruction. The successful outcome of an endopyelotomy depends on the
      preoperative renal function of the involved kidney. Whitaker's test may be used
      for equivocal cases.

PMID- 9933039
TI  - Subepithelial pelvic hematoma of the kidney clinically mimicking cancer: report
      of six cases and review of the literature.
AB  - OBJECTIVES: Renal pelvic subepithelial hematoma is a rare but significant
      clinical mimic of neoplasm. Investigation and treatment of this diagnostic
      problem are uncertain. METHODS: We add 6 patients with this entity to the 15
      previously published cases. All 6 were clinically suspected of having cancer, and
      5 underwent nephrectomy. RESULTS: The most common clinical findings are gross
      hematuria (19 of 21 cases) and acute onset of flank pain (13 of 21 cases).
      Intravenous urogram usually reveals a filling defect at the ureteropelvic
      junction. Pathologic findings include massive subepithelial and peripelvic
      hemorrhage, hydronephrosis, cortical infarcts, and renomegaly. Two of our
      patients have previously undescribed clinical associations, including one who was
      2 weeks postpartum and another with ureteropelvic junction obstruction. In
      addition, our patient with obstruction is the first with subepithelial hematoma
      to be treated successfully with pyeloplasty. CONCLUSIONS: Subepithelial pelvic
      hematoma may be effectively treated with pyeloplasty or partial nephrectomy if
      distinguished from cancer preoperatively. Awareness of this rare entity may allow
      preoperative identification, but this has not been possible to date.

PMID- 9933040
TI  - Laparoscopic radical nephrectomy for renal cell carcinoma: a five-year
      experience.
AB  - OBJECTIVES: To evaluate the efficacy of laparoscopic radical nephrectomy for
      patients with small renal cell carcinoma by comparing the clinical results of
      patients treated laparoscopically with those of patients treated with traditional
      open radical nephrectomy. METHODS: Of 100 patients with localized, small (less
      than 5 cm in diameter) renal cell carcinoma treated by the same surgical team
      between 1992 and 1998, 60 patients underwent laparoscopic radical nephrectomy and
      40 underwent open radical nephrectomy. Of the 60 laparoscopically treated
      patients, the first 11 and the most recent 34 patients were operated on
      transperitoneally and the other 15 retroperitoneally. RESULTS: The mean operative
      time of the laparoscopically treated patients was longer than that of the open
      nephrectomy patients (5.2 versus 3.3 hours, P<0.001). The mean blood loss of the
      laparoscopically treated patients was less than that of the open nephrectomy
      patients (255 versus 512 mL, P<0.001). One laparoscopically treated patient
      needed conversion to open surgery. The time to full convalescence of the
      laparoscopically treated patients was shorter than that of the open nephrectomy
      patients (23 versus 57 days, P<0.001). Two of the 59 laparoscopically treated
      patients and 1 of the 40 open nephrectomy patients had metastatic disease. The
      former 2 are alive with stable disease and the latter died of progressive disease
      11 months after surgery. The 5-year disease-free rate was 95.5% in laparoscopy
      patients and 97.5% in open nephrectomy patients (P = NS). CONCLUSIONS:
      Laparoscopic radical nephrectomy is a less invasive alternative to open surgery
      for patients with localized small renal cell carcinoma.

PMID- 9933041
TI  - Long-term outcome and quality of life after modified pubovaginal sling for
      intrinsic sphincteric deficiency.
AB  - OBJECTIVES: To evaluate the long-term outcome of the modified pubovaginal sling
      (MPVS) procedure and its impact on our patients' quality of life (QOL). METHODS:
      We mailed an outcome questionnaire to 112 female patients who underwent the MPVS
      procedure for complicated type III stress urinary incontinence (SUI), intrinsic
      sphincteric deficiency. Eighty-two responses (73.2%) were obtained, with a mean
      follow-up of 3.4 years (range 0.5 to 8). Forty-four of them have had a follow-up
      for more than 3 years. RESULTS: Of the patients who responded, 86.3% were
      satisfied, and 78% of the patients reported significant improvement; 49.3% were
      dry all the time, 21.9% were occasionally wet, 17.9% were wet with moderate
      activity, and 10.9% were wet all the time. Social activity improved in 74% of the
      patients, and sexual activity improved in 39%. No significant difference was
      noted in continence and satisfaction or QOL. Reviewing the charts of our failures
      (15 patients, 19.2%) revealed that all of them had urge incontinence with or
      without SUI. CONCLUSIONS: The questionnaire results revealed a high satisfaction
      rate and a significant improvement in the QOL of patients with complicated SUI
      who underwent MPVS. The patients remained satisfied over a long follow-up period.
      Failures are mostly associated with urge incontinence and severe irritative
      symptoms.

PMID- 9933043
TI  - Orthotopic neobladder in management of tubercular thimble bladders: initial
      experience and long-term results.
AB  - OBJECTIVES: To describe the indications and long-term results of orthotopic
      bladder replacement for tubercular thimble bladders. METHODS: Four patients (3
      women, 1 man; mean age 32 years) presented with markedly contracted bladders of
      tubercular etiology. The patients had marked lower tract symptoms, and the mean
      bladder capacity was 15 mL. All 4 patients had associated upper tract pathology.
      Four-drug antitubercular treatment (ATT) was started in all 4 patients, and all 4
      underwent surgery 4 weeks later. The procedure performed was a cystectomy and
      orthotopic bladder reconstruction using the ileocecal segment in 3 patients and
      the sigmoid colon in 1. The ureters were implanted into the taenia of the cecum
      or the sigmoid in an antireflux fashion. ATT was continued for a total of 9
      months. RESULTS: All patients had an uneventful postoperative course. After a
      follow-up period ranging from 22 to 54 months (mean 38), the average bladder
      capacity in the 4 patients was 450 mL (range 400 to 600). The mean maximal flow
      rate was 18.3 mL/s. Potency was preserved in the man and all patients were
      continent at last follow-up. The male patient had hypercontinence requiring clean
      intermittent catheterization for a period of 3 months. At last follow-up all
      patients had residual-free micturition. The female patients were able to void to
      completion with a Valsalva maneuver. No patient had symptomatic urinary infection
      or deterioration in renal function. No patient had persistent ureteral reflux or
      stricture. CONCLUSIONS: Cystectomy with orthotopic bladder replacement offers an
      alternative to the urologist treating end-stage tubercular bladders (thimble
      bladders) with a capacity of less than 15 to 20 mL. This treatment removes the
      source of the symptoms, permits anastomosis to healthy tissue of the proximal
      urethra, and addresses lower ureteral pathology at the same time. The long-term
      results in these initial cases are encouraging; however, only a prospective,
      randomized trial can establish whether these advantages actually translate into
      long-term clinical benefit in this group of patients.

PMID- 9933042
TI  - Role of chronic catheterization in the development of bladder cancer in patients
      with spinal cord injury.
AB  - OBJECTIVES: Patients with spinal cord injury (SCI) and chronic indwelling
      catheters are known to be at increased risk of bladder malignancy.
      "Decatheterization" by clean intermittent catheterization, external condom
      catheterization, or spontaneous voiding is thought to reduce the risk by
      decreasing the chronic mucosal irritation and rate of infection. We examined two
      Department of Veterans Affairs (DVA) data bases to test this theory. METHODS: A
      population-based retrospective analysis of invasive treatments for carcinoma of
      the bladder in all DVA hospitals was conducted using computerized inpatient files
      from fiscal years 1988 to 1992. RESULTS: One hundred thirty patients with bladder
      malignancy were identified from a pool of 33,565 patients with SCI (0.39%). All
      130 patients underwent either radical cystectomy (n = 63, 48%) or transurethral
      resection of bladder tumor (n = 67, 52%). The 30-day perioperative mortality and
      overall 5-year survival rates were 2 (1.5%) and 49 (38%) of 130, respectively. Of
      the 130 patients analyzed, 42 (32%) had adequate data available regarding tumor
      pathologic findings and method of bladder management for analysis. The average
      age at diagnosis was 57.3 years. The histologic finding was transitional cell
      carcinoma in 23 (55%), squamous cell carcinoma in 14 (33%), and adenocarcinoma in
      4 (10%) of 42. Bladder management was an indwelling urethral catheter in 18
      (43%), suprapubic catheter in 8 (19%), clean intermittent catheterization in 8
      (19%), and condom catheter in 6 (14%) of 42 patients. Squamous cell carcinoma was
      more common in patients with indwelling urethral catheters and suprapubic tubes
      (11 of 26, 42%) than in those using clean intermittent catheterization, condom
      catheterization, or spontaneous voiding (3 of 16, 19%). CONCLUSIONS: Bladder
      cancer was diagnosed in approximately 0.39% of this large SCI population during a
      5-year period. Most cancers (55%) were transitional cell carcinomas. Squamous
      cell carcinoma was more common in patients with SCI and indwelling catheters than
      those without chronic catheterization. These data continue to suggest that
      avoidance of indwelling catheters, when feasible, is the preferred method of
      bladder management in patients with SCI.

PMID- 9933044
TI  - Elevation of serum level of vascular endothelial growth factor as a new predictor
      of recurrence and disease progression in patients with superficial urothelial
      cancer.
AB  - OBJECTIVES: To determine whether the serum vascular endothelial growth factor
      (VEGF) level in patients with urothelial cancer could be used as a predictor of
      recurrence and disease progression. METHODS: Serum levels of VEGF in 51 healthy
      controls and 135 patients with urothelial cancer (81 superficial and 54 invasive
      cancers) were measured using a sandwich enzyme immunoassay, and the results were
      analyzed with respect to several clinicopathologic factors. RESULTS: Significant
      differences in the serum VEGF level were observed between healthy controls and
      patients with superficial urothelial cancer (34+/-12 pg/mL versus 49+/-27 pg/mL,
      P<0.001) and between healthy controls and patients with invasive cancer (34+/-12
      pg/mL versus 51+/-35 pg/mL, P<0.001), whereas there was no significant difference
      in the serum VEGF level between superficial and invasive cancers (49+/-27 pg/mL
      versus 51+/-35 pg/mL, P = 0.31). Among patients with superficial cancer, the
      disease-free survival rate of patients with elevated serum levels of VEGF was
      significantly lower than that of patients with normal levels (P<0.05). The
      progression-free survival rate of superficial cancer patients with elevated serum
      levels of VEGF was also significantly lower than that of patients with normal
      levels (P<0.01). In addition, Cox's multivariate analysis revealed that the
      elevation of serum VEGF level was strongly associated with disease-free survival
      and progression-free survival in patients with superficial cancer (P<0.05).
      CONCLUSIONS: The results of this study suggest that the elevation of serum VEGF
      level could be used as a new independent predictor of recurrence and disease
      progression in patients with superficial urothelial cancer.

PMID- 9933045
TI  - Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the
      bladder.
AB  - OBJECTIVES: To retrospectively evaluate the usefulness of transurethral resection
      of bladder tumor (TURBT) and intravesical instillation for pT1bG3 transitional
      cell carcinoma of the urinary bladder. METHODS: Between May 1984 and May 1997, 45
      patients with pT1bG3 transitional cell carcinoma of the urinary bladder underwent
      TURBT and intravesical instillation with bacillus Calmette-Guerin (BCG) or other
      anticancer agents. Random biopsy was carried out in 37 patients. The recurrence
      free survival rate was determined by tumor size, number of tumors, lymphovascular
      invasion, and drugs used for intravesical instillation. The median follow-up
      period was 63 months (range 4 to 145) after the initial TURBT. RESULTS: Of 37
      patients who underwent random biopsy, concomitant carcinoma in situ was detected
      in 18 patients (48.6%). The incidence of concomitant CIS was significantly higher
      in patients with multiple tumors (P = 0.029). Vesical recurrence was noted in 16
      patients (35.6%). The overall 1-, 3-, and 5-year recurrence-free survival rates
      were 88.5%, 66.7%, and 66.7%, respectively. Progression (muscular invasion)
      occurred in only 2 patients (4.4%). Total cystectomy was performed in 4 patients,
      including the 2 patients with progressive disease, and 2 patients with recurrent
      CIS that resisted BCG therapy. None of the patients died of bladder cancer.
      CONCLUSIONS: Our results suggest that aggressive attempts at initial or
      subsequent TURBT combined with BCG therapy achieved good control of pT1bG3
      transitional cell carcinoma of the urinary bladder.

PMID- 9933046
TI  - Evaluation of patients with bladder outlet obstruction and mild international
      prostate symptom score followed up by watchful waiting.
AB  - OBJECTIVES: To examine the variability of bladder outlet obstruction and mild
      lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH)
      followed up by watchful waiting. METHODS: The International Prostate Symptom
      Score (IPSS) has four questions related to voiding symptoms and three related to
      filling symptoms. Scores of 0 to 7, 8 to 19, and 20 to 35 represent mild,
      moderate, and severe symptoms, respectively. Over a period of 36 months the IPSS
      questionnaire was administered to 479 patients 50 to 81 years old (mean age 63)
      with BPH. A pressure-flow study was used to determine the presence of bladder
      outlet obstruction. On the basis of their scores, the patients were classified
      into 50 with mild, 227 with moderate, and 202 with severe symptoms. In the
      present study only patients with a mild score were analyzed. RESULTS: Of 50
      patients with mild symptoms, 16 (32%) had bladder outlet obstruction. After a
      period of 9 to 22 months (mean 17) of watchful waiting, these 16 patients were
      reviewed. Twelve (75%) of the 16 had bladder outlet obstruction reconfirmed by
      pressure-flow studies, and 3 (18.8%) of 16 had increased symptoms (moderate
      symptomatic) and underwent treatment (1 began pharmacologic treatment, and 2
      chose transurethral resection). A total of 4 (25%) of 16 patients still had mild
      voiding disturbances and refused the second urodynamic evaluation. The remaining
      34 patients with no obstruction had annual routine follow-up and had persistent
      mild symptom scores and normal uroflowmetric results. These patients did not
      undergo another pressure-flow evaluation. CONCLUSIONS: A pressure-flow study is
      routinely avoided in patients with a mild IPSS. From symptoms alone it was not
      possible to diagnose bladder outlet obstruction in these patients. Pressure-flow
      studies and symptom profiles measure different aspects of the clinical condition.
      After a mean follow-up of 17 months of watchful waiting, 13 (81.2%) of 1 6
      patients were clinically stable. Because the need for therapy is dictated by
      quality of life, it is difficult to propose treatment for patients with minimal
      symptoms, even in the presence of bladder outlet obstruction.

PMID- 9933047
TI  - Electrovaporization as a treatment modality for transurethral resection of the
      prostate: influence of generator type.
AB  - OBJECTIVES: To study the influence of the electrosurgical generator on the
      vaporization efficacy during electrovaporization (EVAP) using different
      vaporization elements. METHODS: Electrical properties of human prostatic (in
      vivo) and bovine myocardium (in vitro) tissue were measured under
      electroresection and electrovaporization conditions. The effective output power
      of four different generators ("old generation" Force 4 and Force 40 and "new
      generation" Force 300 and Force FX) was measured at different impedance loads. In
      vitro, the coagulation and vaporization capabilities of the electrosurgical
      generators in combination with resection and vaporization elements were studied
      on homogeneous tissue (bovine myocardium). RESULTS: The electrical impedance of
      human prostatic tissue and bovine myocardium increases from 400 to 1000 ohms when
      coagulated. The effective output power of the old generation electrosurgical
      devices depends strongly on tissue impedance. This implies that working on
      already coagulated tissue using such devices is not well controlled and not
      reproducible. By contrast, new generation electrosurgical devices correct for the
      higher impedance of coagulated tissue, thus delivering constant output power and
      corresponding tissue effects. CONCLUSIONS: For an effective application of the
      EVAP technique, the use of a new generation impedance independent electrosurgical
      unit is highly recommended.

PMID- 9933048
TI  - Results of high-energy transurethral microwave thermotherapy in patients
      categorized according to the American Society of Anesthesiologists operative risk
      classification.
AB  - OBJECTIVES: To evaluate the relation between the American Society of
      Anesthesiologists (ASA) classification and response to transurethral microwave
      thermotherapy (TUMT) in patients with lower urinary tract symptoms and benign
      prostatic hyperplasia (BPH). METHODS: Two hundred forty-seven patients with
      symptomatic BPH treated with high-energy TUMT were scored retrospectively for ASA
      status. Student's t test was used to determine differences in improvement at each
      point of follow-up between patients classified as ASA 1 or 2 and patients
      classified as ASA 3 or 4. Logistic regression analysis was performed to assess
      the predictive value of ASA status for response using the World Health
      Organization response evaluation criteria for International Prostate Symptom
      Score, maximal flow rate, and urodynamic obstruction. RESULTS: There was a
      significant improvement in objective and subjective parameters at 12, 26, and 52
      weeks of follow-up in both ASA 1 and 2 patients and ASA 3 and 4 patients. There
      was no difference in objective and subjective improvement between both groups at
      each point of follow-up. Objective and subjective improvement in ASA 3 and 4
      patients with cardiovascular disease and ASA 3 and 4 patients with
      noncardiovascular disease was the same, although patients with cardiovascular
      disease received less energy during TUMT. Using logistic regression analysis, ASA
      classification was not predictive of response after high-energy TUMT.
      CONCLUSIONS: There is no relation between ASA classification and outcome after
      high-energy TUMT. Because these patients are considered at high risk of
      perioperative complications and postoperative morbidity, TUMT could contribute
      considerably to the treatment of BPH in this specific group of patients.

PMID- 9933049
TI  - Clinical correlation of maximal urinary flow rate and plasma doxazosin
      concentrations in the treatment of benign prostatic hyperplasia. Multicenter
      Study Group.
AB  - OBJECTIVES: To investigate the relationship among doxazosin dose, plasma
      concentration, and clinical response in 248 hypertensive men with benign
      prostatic hyperplasia (BPH) in a 16-week, placebo-controlled, double-blind study.
      METHODS: After a 2-week placebo run-in period, patients were randomized to
      treatment with either doxazosin (titrated to doses of 2, 4, 8, or 12 mg once
      daily) or placebo. After 6, 10, and 14 weeks, plasma concentrations of doxazosin
      were measured at 2 to 6 hours (peak) and approximately 24 hours (trough) after
      dosing. Changes in maximal urinary flow rate (Qmax) compared with baseline were
      measured at the same time points. Patients recorded their symptoms in a daily
      diary and completed a questionnaire at weeks 2, 8, and 16 to assess both
      obstructive and irritative BPH symptoms. In addition, BPH symptoms were assessed
      by the investigator at each study visit. RESULTS: Steady-state peak and trough
      plasma doxazosin concentrations were achieved by 6 weeks of therapy and were
      maintained between 6 and 14 weeks of active treatment. Peak and trough plasma
      concentrations increased linearly within the dose range of 2 to 12 mg and were
      positively correlated with a corresponding mean improvement in Qmax (P = 0.001
      and P = 0.008, respectively), consistent with a 24-hour once-daily dosing of
      doxazosin. Clinical response to doxazosin plateaued at peak and trough plasma
      concentrations of between 60 and 80 ng/mL and 25 ng/mL, respectively,
      corresponding to a dose of 8 mg daily. Patient assessment of obstructive BPH
      symptoms showed significant improvement in the 4- and 8-mg doxazosin treatment
      groups compared with placebo. CONCLUSIONS: In patients with BPH, both doxazosin
      plasma concentration and Qmax increased linearly with increasing dose, in the
      range of 2 to 8 mg daily. The maximal therapeutic dosage of doxazosin would
      appear to be 8 mg in this group of BPH patients. Further studies are required to
      support these findings.

PMID- 9933050
TI  - Failure to void after transurethral resection of the prostate and mode of
      presentation.
AB  - OBJECTIVES: Contemporary audits and reviews of outcome after transurethral
      resection of the prostate (TURP) make little reference to failure to void
      following catheter removal after this operation. There have been few reports of
      the likelihood of a successful trial without a catheter after TURP related to
      mode of presentation. We report the results of a retrospective review of outcome
      of TURP related to mode of presentation, age, and prostate histologic findings in
      a consecutive series of patients in a London Teaching Hospital. METHODS: A
      consecutive series of 379 patients (381 TURPs) was reviewed to document the
      incidence of and risk factors for failure to void following initial trial without
      a catheter after TURP. RESULTS: Twelve percent of men failed to void after TURP
      on the initial trial without a catheter. In those patients presenting with lower
      urinary tract symptoms, there were no instances of failure to void. Ten percent
      of patients with acute retention (painful inability to void, urine volume less
      than 800 mL), 38% with chronic retention (maintenance of spontaneous voiding,
      bladder volume greater than 500 mL), and 44% with acute on chronic retention
      (painful retention, urine volume greater than 800 mL) failed to void after TURP.
      Only 1% of patients required management by long-term catheterization. Failure to
      void on catheter removal was not related to age or prostate histologic findings.
      CONCLUSIONS: Bladder volume at initial presentation in patients with urinary
      retention provides important information about the likelihood of re-establishing
      spontaneous voiding catheter removal following TURP. Patients should be warned
      that there is a significant chance of failure to void after TURP, the exact risk
      depending on their mode of presentation, but that most will ultimately not
      require a permanent indwelling catheter.

PMID- 9933051
TI  - Diagnosis and therapeutic management of 18 patients with prostatic abscess.
AB  - OBJECTIVES: Our retrospective study aimed to analyze the findings and therapeutic
      strategies in 18 men who were admitted to our department as outpatient emergency
      cases with prostatic abscess. METHODS: During the period 1985 to 1997, prostatic
      abscess was diagnosed in 18 patients (mean age 48 years, range 20 to 68) on the
      basis of evidence of fluctuation at digital rectal examination and transrectal
      ultrasound (TRUS) findings. Diagnostic workup included analysis of midstream
      urine and abscess fluid for leukocytes and pathogens. Therapeutic options were
      conservative treatment and/or draining procedures. RESULTS: Predisposing diseases
      were found in 13 men. Fluctuation at digitorectal palpation was present in 15
      patients. In 3 patients, diagnosis was based on TRUS. All men demonstrated
      leukocytes in their midstream urine. Causative pathogens in midstream urine were
      found in 11 patients. In 3 men, additional microbiologic evaluation of abscess
      fluid revealed uncommon pathogens. All patients received antibiotic treatment.
      Nine men with monofocal abscess less than 1 cm in diameter were treated with
      antibiotic therapy and a suprapubic catheter. Surgical drainage (transperineal or
      transrectal puncture, partly guided by TRUS, or transurethral unroofing) was
      performed in 12 patients and included 3 patients in whom conservative treatment
      failed. CONCLUSIONS: Our data confirm the importance of predisposing factors in
      the pathogenesis of prostatic abscess. Medical history and analysis of midstream
      urine indicated a diagnosis that was confirmed by digital palpation. In some
      cases, TRUS may improve diagnosis and treatment. Although both operative and
      conservative therapy strategies appear feasible, prostatic abscess chiefly
      requires individually selected drainage procedures.

PMID- 9933052
TI  - Results of transition zone biopsy in black and white men with suspected prostate
      cancer.
AB  - OBJECTIVES: To determine whether biopsy-detectable transition zone tumors are
      more common in black than in white men with suspected Stage T1c and T2 prostate
      cancer. METHODS: We performed a prospective study of transition zone prostate
      biopsy (TZ biopsy) in 1 78 black and 261 white men who had not undergone previous
      prostate biopsy and in 61 black and 65 white men who had undergone one benign
      sextant peripheral zone prostate biopsy (PZ biopsy). RESULTS: The mean age of the
      239 black and 326 white study patients was 68.6+/-7.4 and 67.2+/-7.2 years,
      respectively (P = 0.02), the mean prostate-specific antigen (PSA) was 8.4+/-7.4
      and 6.4+/-5.4 ng/mL, respectively (P = 0.003), and the mean PSA density was
      0.20+/-0.23 and 0.16+/-0.16 ng/mL/mL, respectively (P = 0.006). Overall, cancer
      was diagnosed by TZ biopsy only in 7 black men (3%) and in no white men (0%) (P =
      0.003). However, cancer detection with a TZ biopsy only was not significantly
      different in the black and white men when controlled for age, PSA, or PSA density
      (P>0.90). A TZ biopsy only detected cancer in 1% of patients who had not
      undergone prior PZ biopsy and in 2% of patients who had undergone prior PZ
      biopsy. Of the seven cancers detected with TZ biopsy, six (86%) had a Gleason
      score of 2 to 6. CONCLUSIONS: Prostate cancer detection with a TZ biopsy only is
      not common and when controlled for confounding variables is the same in black and
      white men. The preferential use of TZ biopsies in black men is not warranted, and
      the low diagnostic yield argues against routine use of the biopsy technique in
      men of either race.

PMID- 9933053
TI  - Follow-up of atypical prostate needle biopsies suspicious for cancer.
AB  - OBJECTIVES: To determine both how the diagnosis of an atypical biopsy influences
      a urologist's decision to repeat the biopsy and the outcome of rebiopsy. METHODS:
      Of 200 atypical biopsies that we confirmed from outside consultations to the
      Johns Hopkins Hospital from 1992 to 1993, we were able to retrieve follow-up
      information for 144 cases. Each atypical biopsy was evaluated for the reason for
      atypia (atrophic glands, rule out [r/o] adenosis, atypical not otherwise
      specified [NOS; insufficient cytologic and/or architectural atypia], r/o
      prostatic intraepithelial neoplasia [PIN], inflammation, crush artifact) and a
      favored diagnosis (cancerous, benign, and undetermined). RESULTS: Of the 144
      atypical biopsies, 92 were rebiopsied (63.9%). The time from the initial atypical
      biopsy to rebiopsy ranged from 0.5 months to 3 years (63% less than 6 months; 39%
      less than 3 months). Rebiopsy revealed carcinoma in 48.9%, benign in 38%,
      atypical in 8.7%, and PIN in 4.4%. The median prostate-specific antigen (PSA)
      value was lower in men who did not undergo a repeat biopsy (6 versus 7.8) (rank
      sum analysis, P = 0.04). No correlation was found between PSA level and results
      of the rebiopsy. Of the atypical biopsies in which cancer was favored, 61% were
      cancerous on rebiopsy versus 33% where a benign process was favored. The three
      reasons for atypical biopsies that seemed to correlate with outcome of rebiopsy
      were atypical NOS (68% cancer on rebiopsy); inflammation (63% cancer on
      rebiopsy); and r/o adenosis (36% cancer on rebiopsy). CONCLUSIONS: Although 48.9%
      of the rebiopsied cases were cancerous, only 63% of men underwent rebiopsy,
      raising a concern that cancers are being missed in those cases not rebiopsied
      after an atypical diagnosis. Although there was a trend for serum PSA to
      correlate with outcome of rebiopsy, this correlation was not significant, and
      even men with serum PSA less than 4 ng/mL had a 33% risk of cancer on rebiopsy.
      Although histologic features of the atypical foci may be useful as factors in
      determining the urgency for rebiopsy, they also were not statistically
      significant in predicting outcome. Men with atypical diagnoses should undergo
      rebiopsy regardless of serum PSA levels and regardless of why the lesions were
      atypical.

PMID- 9933054
TI  - Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with
      normal digital rectal examinations and prostate-specific antigen levels less than
      10 ng/mL.
AB  - OBJECTIVES: Most men diagnosed with prostate cancer in 1998 presented with a
      normal digital rectal examination (DRE) and minimal elevations in serum prostate
      specific antigen (PSA) (less than 10 ng/mL). Considerable attention is often
      given toward identifying small hypoechoic (less than 0.2 cm3) lesions at the time
      of transrectal ultrasound-guided prostate biopsy. We sought to determine the
      significance of these lesions and whether an additional biopsy of this area is
      clinically useful. METHODS: A prospective data base containing detailed
      information on 614 biopsies performed by a single urologist was examined. All
      patients with a hypoechoic lesion underwent sextant prostate biopsy plus a
      separately labeled core directed through the hypoechoic area. Eighty-one patients
      who fit the following criteria were assessed: PSA less than 10 ng/mL, normal DRE,
      and hypoechoic lesion volume less than 0.2 cm3. RESULTS: The mean age of this
      group was 63.5 years, and the mean PSA was 7.1 ng/mL. Of the 81 patients with
      small hypoechoic lesions, 20 (24.7%) were positive for cancer in at least one
      prostatic core. Of the 81 hypoechoic area biopsies (HABs), 14 (17.3%) were
      positive for cancer; 1 (1.2%) demonstrated high-grade prostatic intraepithelial
      neoplasia, and 66 (81 .5%) were negative. In 11 of the patients (78.6%) with
      positive HABs, at least one additional core was positive for cancer. In 3 of the
      patients (21.4%) with positive HABs, no additional cores were positive for cancer
      (P<0.05). CONCLUSIONS: A significant proportion of small hypoechoic lesions in
      patients with early T1c prostate cancer are positive for malignancy. Although the
      overall yield of separate hypoechoic area biopsy is low (3.7%), approximately 15%
      of cancers would be missed if directed HABs were not performed (P<0.05).
      Identification and biopsy of small hypoechoic lesions are indicated in this group
      of patients.

PMID- 9933055
TI  - Self-assessed health-related quality of life in men being treated for prostate
      cancer with radiotherapy: instrument validation and its relation to patient
      assessed bother of symptoms.
AB  - OBJECTIVES: To develop a psychometrically valid and clinically useful
      questionnaire to assess health-related quality of life (HRQOL) in patients with
      prostate cancer (PCa) undergoing external beam radiotherapy. The most important
      factors in three dimensions (bowel function [BF], urinary function [UF], and
      sexual function [SF]) were identified by patient survey. METHODS: Three HRQOL
      dimensions were assessed using Likert-type questions. Responses were analyzed by
      factor analysis to create HRQOL scales. Reliability and validity of the scales
      were assessed. Because patients can suffer symptoms yet not report their lives to
      be affected, the scales were compared with patient-reported bother. RESULTS: Two
      scales were identified within each dimension: BF, urgency and daily living; UF,
      urgency and weakness of stream; and SF, interest/satisfaction and impotence.
      Cronbach's alpha for the scales ranged from 0.63 to 0.94, and item-scale
      correlations and item-scale divergence correlations supported scale validity.
      Rising median scores correlated with rising levels of perceived bother.
      CONCLUSIONS: The questionnaire is a suitable tool for assessing HRQOL in three
      distinct dimensions for patients undergoing radiotherapy for PCa. Six dimensions
      of HRQOL were found to be related to bother, suggesting important relationships
      to be monitored for patients. Urgency of bowel movements, urgency of urination,
      and level of interest/satisfaction in sex correlated most strongly with bother.

PMID- 9933056
TI  - Lymph node size does not correlate with the presence of prostate cancer
      metastasis.
AB  - OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph
      node metastasis. METHODS: We reviewed 980 patients who underwent radical
      retropubic prostatectomy with bilateral pelvic lymph node dissection for
      clinically localized prostate cancer, of whom 63 had lymph node metastases. A
      comparable group of patients with prostate cancer undergoing radical
      prostatectomy who did not have lymph node involvement was identified using the
      following parameters: serum prostate-specific antigen level, clinical and
      pathologic stage, and pre- and postoperative Gleason score. The axial and
      longitudinal dimensions of the nodes from patients with and without metastases
      were analyzed to assess the significance of lymph node size in predicting the
      presence of metastases. All patients had negative preoperative computed
      tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48
      had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A
      total of 76 metastatic and 92 negative lymph nodes were identified from the
      patients with and without metastatic nodes, respectively. The mean nodal
      longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for
      positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size
      was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and
      negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size
      was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size
      should not be used as a surrogate for the presence of lymph node metastases.
      Although no patient had enlarged lymph nodes by CT scan criteria (greater than
      1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node
      metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

PMID- 9933057
TI  - Should Gleason score 7 prostate cancer be considered a unique grade category?
AB  - OBJECTIVES: To evaluate pathologic characteristics and biochemical survival rate
      differences between patients with Gleason score 6 or less, 7, and 8 or more
      prostate cancer. METHODS: A total of 652 patients who underwent a radical
      prostatectomy for clinically localized prostate cancer between March 1991 and
      December 1995 were selected for this study. Patients who underwent neoadjuvant or
      adjuvant hormonal therapy or radiotherapy were excluded. Clinical and pathologic
      data were obtained from our prostate cancer data base. Serum prostate-specific
      antigen (PSA) level, pathologic stage, and disease-free survival (DFS) were
      analyzed between the three Gleason score groups. RESULTS: The overall mean
      pretreatment serum PSA level was 12.9 ng/mL, being 8.4, 13.4, and 23 ng/mL for
      Gleason score 6 or less, 7, and 8 or more prostate cancers, respectively (P =
      0.0001). Of patients with specimen Gleason score 6 or less, 7, and 8 or more,
      pathologic organ-confined disease was present in 69.4%, 43.1 %, and 9.2%,
      respectively (P = 0.001). Extraprostatic extension was present in 30.6%, 56.9%,
      and 90.8% (P = 0.0001); positive surgical margins, considered independently from
      the other pathologic findings, were present in 31 %, 47.6%, and 67.8% of patients
      with Gleason score 6 or less, 7, and 8 or more, respectively (P = 0.0001). DFS
      was 34.5% for patients with Gleason score 8 or more, 75% for Gleason score 7, and
      91.2% for Gleason score 6 or less prostate cancers, at a median follow-up of 34.2
      months (P = 0.0001). On multivariable analysis, after adjusting for serum PSA
      level (10 or less or more than 10 ng/mL) and pathologic stage, Gleason score (6
      or less, 7, 8 or more) remained a statistically significant predictor of DFS (P =
      0.0001). CONCLUSIONS: Patients with Gleason score 7 prostate cancer should be
      considered a specific prognostic category. We believe that this distinction is
      critical to obtain more reliable results from prostate cancer analyses about
      prognosis of patients treated with curative intent.

PMID- 9933058
TI  - Androgen receptor gene CAG repeat length varies in a race-specific fashion in men
      without prostate cancer.
AB  - OBJECTIVES: Preliminary studies suggest that black men have shorter androgen
      receptor CAG repeat length compared with non-Hispanic whites. Because decreased
      CAG repeat length (in particular less than 20 repeats) may be associated with
      increased prostate cancer risk, these findings are potentially important in
      providing a hypothesis to explain the increased risk of prostate cancer in black
      men. METHODS: CAG repeat length in the androgen receptor (exon one) was
      determined by a polymerase chain reaction method in 130 non-Hispanic white and 65
      black men. All men had prostate-specific antigen levels less than 4 ng/mL and
      normal digital rectal examinations. Men self-classified themselves into racial
      categories by a standardized questionnaire. RESULTS: For whites, the mean +/- SD,
      median, and range of CAG repeat length were 21.0+/-3.0, 21, and 9 to 28,
      respectively. For blacks, the mean +/- SD, median, and range of CAG repeat length
      were 19.0+/-3.0, 19, and 13 to 26, respectively. The mean and median CAG repeat
      length in blacks were statistically significantly shorter than in whites. Black
      men were twice as likely as whites to have fewer than 20 CAG repeats (56.9%
      versus 28.5%, P = 0.0001). CONCLUSIONS: These data unequivocally demonstrate that
      androgen receptor gene CAG repeat length varies in a race-specific manner in men
      without evidence of prostate cancer.

PMID- 9933059
TI  - Aneuploidy index in blood: a potential marker for early onset, androgen response,
      and metastasis in human prostate cancer.
AB  - OBJECTIVES: To investigate whether the frequency of chromosome abnormalities in
      peripheral blood lymphocytes defined as the aneuploidy index in blood (AnIB) can
      be used as a clinical marker of early age onset, androgen response, and
      metastasis in human prostate cancer. METHODS: Peripheral blood samples were
      collected from 80 patients with prostate cancer, and chromosome preparations were
      made from 72-hour cultures after mitotic block. The AnIB of 59 informative cases
      was compared with several parameters, including age at disease onset, Gleason
      grade of tumor, clinical stage of tumor, metastasis, and prostate-specific
      antigen (PSA) level. RESULTS: Patients with AnIB levels greater than 3 had a
      significantly higher incidence of metastasis (P = 0.022), androgen-independent
      disease (P = 0.002), and early age at disease onset (age at diagnosis less than
      65 years) (P = 0.002) compared with the patients with lower AnIB (less than 3)
      levels. In addition, patients with AnIB levels greater than 5 had higher PSA
      levels (greater than 20 ng/mL) (P = 0.029) than patients with AnIB levels less
      than 5. CONCLUSIONS: Chromosome abnormalities can be detected in the peripheral
      lymphocytes of patients with prostate cancer, and AnIB can be used as an early
      diagnostic and predictive marker for prostate cancer metastasis and androgen
      independent disease.

PMID- 9933060
TI  - Conservative surgical therapy for penile and urethral carcinoma.
AB  - OBJECTIVES: Invasive penile and urethral tumors are traditionally treated with
      aggressive excision that requires involved organ and adjacent organ sacrifice. An
      alternative approach seeks to completely excise the tumor with adequate margins
      while preserving form and function of the organ. We present 6 patients who
      underwent such organ-sparing surgery. METHODS: Six selected cases (4 penile and 2
      urethral) are presented with operative photographs and pertinent data. RESULTS:
      Three distal tumors of the penis were treated with excision limited to the glans
      with histopathologic findings of verrucous carcinoma, melanoma, and angiosarcoma.
      One patient with squamous cell carcinoma of the distal shaft refused partial
      penectomy and underwent a local wedge resection. A patient with locally advanced
      bulbourethral transitional cell carcinoma (TCC) refused cystourethrectomy and
      underwent an anterior urethrectomy and perineal urethrostomy. A 48-year-old woman
      with an adenocarcinoma contained in a very distal urethral diverticulum underwent
      simple diverticulectomy and excision of distal urethra. Postoperative voiding and
      sexual function were well preserved. Follow-up was 12 to 48 months. The patient
      with angiosarcoma died of lung metastases at 48 months with no local disease, and
      the patient with bulbourethral TCC developed pelvic disease at 12 months with no
      local recurrence and died of metastases at 25 months. CONCLUSIONS: Organ-sparing
      surgery is appropriate in selected patients on the basis of stage and location,
      high risk of distant failure, and patient disposition. Close follow-up is
      necessary. Comanagement with reconstructive and oncologic specialists optimizes
      results and outcomes.

PMID- 9933061
TI  - Penectomy: a technique to reduce blood loss.
AB  - OBJECTIVES: Hemorrhage is potentially a major complication of partial or total
      penectomy that may result in the need for blood transfusion. The surgical
      technique of penectomy was evaluated to determine whether modifications may lead
      to reduced blood loss. METHODS: A simple technique was used to minimize blood
      loss during penectomy. A Penrose tourniquet was used to minimize subcutaneous
      bleeding, incised urethral edges were oversewn, and a noncrushing vascular clamp
      was placed across the corporal bodies before transection. RESULTS: Placement of a
      noncrushing vascular clamp on the corporal bodies before penectomy greatly
      reduced blood loss in patients who required either a partial or total penectomy.
      The procedure was performed in a clear field. CONCLUSIONS: By modification of the
      surgical technique of partial and total penectomy, it is possible to minimize the
      potential complication of hemorrhage.

PMID- 9933062
TI  - Reasons for discontinuing intracavernous injection therapy with prostaglandin E1
      (alprostadil).
AB  - OBJECTIVES: To clarify the reasons why experience with self-injection therapy for
      erectile dysfunction shows high dropout rates. METHODS: We studied 86 patients 36
      to 76 years old who had been on home treatment for at least 3 months. Sixty-nine
      patients (80%) were continuing to use injections, and 17 (20%) had discontinued
      the treatment. Patients were evaluated by interview and clinical examination.
      RESULTS: Patients still in the program used one injection every 2 weeks, and
      those who had given up treatment had used one injection in 3 weeks (P = 0.31).
      They were in the program for 39+/-27 and 16+/-22 months (P = 0.002),
      respectively, and had used 50 (95% confidence interval [CI] 21 to 91) versus 12
      (95% CI 4 to 20) injections, respectively (P<0.0001). Injections producing
      unsatisfactory penile rigidity, prolonged erections, hematoma at injection site,
      corporal fibrosis, secondary penile deviation, and mean estimated duration of a
      pharmacoinduced erection showed no significant differences. Patient satisfaction
      (P = 0.02), estimated partner satisfaction (P = 0.02), increase in self-esteem (P
      = 0.01), and negligible effort in performing injections (P = 0.001) all showed
      significantly better results for those still in the program. CONCLUSIONS: Reasons
      for dropout from self-injection therapy are not based on objective side effects
      and discomfort. Patients leaving the program are less motivated, less satisfied
      with the quality of pharmacoinduced sexuality, consider the effort to perform
      injections to be substantial, and have not achieved improved self-esteem.

PMID- 9933064
TI  - Primary nocturnal enuresis: a new approach to conditioning treatment.
AB  - OBJECTIVES: Conditioning treatment is the most effective therapy for nocturnal
      enuresis, precluding the use of drugs. An ordinary alarm clock can be used as an
      enuresis alarm. We sought to assess its clinical utility as a new means of
      conditioning treatment. METHODS: Using the ordinary home alarm clock, 125
      enuretic children were enrolled into two treatment groups. Group I included 70
      children who set the alarm so as to get up and void in the toilet at a critical
      time when the bladder was full and they were still dry. Group II included 55
      children who used the alarm to be awakened for voiding after 2 to 3 hours of
      sleep regardless of whether they were dry or wet. All children were motivated to
      use the alarm clock continuously for 4 months. RESULTS: Initial success was
      achieved in 54 (77.1%) of 70 group I and 34 (61.8%) of 55 group II children.
      Three months after treatment was stopped, success was still maintained in 46
      (65.7%) and 31 (56.4%) children in groups I and II, respectively, but dropped to
      41 (58.6%) and 29 (52.7%), respectively, after 6 months. The relapse rate after 3
      and 6 months was 14.8% and 24.1% for group I and 8.8% and 14.7% for group II,
      respectively. CONCLUSIONS: The ordinary alarm clock performs as well as currently
      used enuresis alarms. It is an effective, elective, noncontact alarm that does
      not wait for bedwetting to initiate a conditioning reflex. It is both reliable
      and safe.

PMID- 9933063
TI  - Duplicate bladder exstrophy: a unique approach to initial repair.
AB  - OBJECTIVES: To describe a unique approach to the management of duplicate bladder
      exstrophy combining initial bladder closure and epispadias repair. Bladder
      exstrophy has been successfully managed by staged surgical repair with early
      bladder closure, subsequent epispadias repair, and, finally, bladder neck
      reconstruction. Duplicate bladder exstrophy is a rare variant of the exstrophy
      complex with fewer than 20 cases reported. METHODS: A male newborn presented with
      the appearance of both bladder exstrophy and a ruptured omphalocele. Repair of
      the omphalocele and bilateral orchiopexy was performed shortly after birth, but
      bladder closure was delayed until there was complete healing of the omphalocele
      defect, and the investigators believed the infant was ready for abdominal wall
      and bladder exstrophy closure. At age 8 months, bladder closure was performed
      with the intraoperative finding of a duplicate bladder lying posterior to the
      exstrophied bladder. The left ureter drained on the exstrophic bladder plate, and
      the right ureter drained into the posterior (internalized) duplicate bladder.
      After anterior innominate and vertical iliac osteotomies, the left ureter was
      reimplanted into the posterior bladder. A portion of the exstrophied bladder was
      then tubularized to construct a neourethra of the epispadic penis. RESULTS: The
      child has done well with an excellent cosmetic appearance of the abdominal wall
      and a straight phallus. The bladder subsequently required a Mitrofanoff-type
      continent stoma along with bladder augmentation, which was performed at the time
      of his Young-Dees-Leadbetter bladder neck reconstruction (age 3.5). The child is
      currently continent but requires intermittent clean catheterization through his
      appendicovesicostomy. CONCLUSIONS: The investigators report a unique and
      unexpected variant of bladder exstrophy and its successful management.

PMID- 9933065
TI  - New technique for antegrade collagen injection for post-radical prostatectomy
      stress urinary incontinence.
AB  - A new modification for antegrade collagen injection into the bladder neck is
      described. A 16F Rusch suprapubic catheter is used to access the bladder. A 15.5F
      Storz cystoscope is then placed through the sheath and the collagen injection
      needle is then placed through the cystoscope in the usual manner. This technique
      permits more rapid bladder access with less bleeding and leakage of irrigation
      fluid than using guide wires and Amplatz dilators.

PMID- 9933066
TI  - Use of a laparoscopic insufflation port for ileal conduit endoscopy.
AB  - We present an effective and simple technique for performing endoscopy of an ileal
      conduit. With a laparoscopic insufflation port in the stoma, a flexible
      cystoscope or ureteroscope can be inserted. The one-way valve of the port
      prevents leakage of irrigation fluid and allows the conduit to distend for
      optimal visualization. This technique is particularly useful when access to the
      upper urinary tracts is needed.

PMID- 9933067
TI  - Giant penile cavernous hemangioma with intrapelvic extension.

PMID- 9933068
TI  - Ureteric calculus diagnosed by retrograde ureterography during an intravenous
      urogram.

PMID- 9933069
TI  - Azoospermia due to aperistalsis of the vas deferens: successful treatment with
      pseudoephedrine.
AB  - Three patients presenting with infertility were found to have low volume
      azoospermia. All 3 were taking sympatholytic medications; 2 were taking
      antipsychotics and 1 was taking an alpha-blocker. Low volume azoospermia may
      result from the use of sympatholytic medications, which cause aperistalsis of the
      adrenergically innervated vas deferens and seminal vesicles. Two patients had
      normal spermatogenesis on biopsy and were unobstructed on vasography. In 1
      patient, biopsy and vasography were avoided. Pseudoephedrine, a sympathomimetic
      agent, was given to all 3 patients, resulting in marked improvement in semen
      analysis parameters. A trial of pseudoephedrine can obviate the need for biopsy
      and vasography in such patients.

PMID- 9933070
TI  - Pelvic arteriovenous malformation mimicking seminal vesicle cyst.
AB  - Congenital pelvic arteriovenous malformations are rare entities, especially in
      males. Presenting symptoms, if any at all, are commonly a mass, thrill, bruit, or
      pain. Treatment options include surgical extirpation, embolization, or a
      combination of both. This case provides support for the last option in a patient
      presenting with symptoms localized to the seminal vesicles.

PMID- 9933072
TI  - Thoracolumbar accessory penis: etiology, diagnosis, and management.
AB  - Human sacral appendages have rarely been reported. We present a neonate with a
      thoracolumbar appendage resembling a penis, and discuss the nature of the anomaly
      and its diagnosis and management.

PMID- 9933071
TI  - Dramatic rise in prostate-specific antigen after androgen replacement in a
      hypogonadal man with occult adenocarcinoma of the prostate.
AB  - We present the case of a hypogonadal patient in whom a 20-fold increase in
      prostate-specific antigen and a palpable prostatic nodule developed 6 months into
      the administration of intramuscular testosterone.

PMID- 9933073
TI  - Role of adhesion molecules in bladder cancer: an important part of the jigsaw.
AB  - There is a growing body of evidence suggesting that alterations in the adhesion
      properties of neoplastic cells may play a pivotal role in the development and
      progression of bladder cancer. Loss of intercellular adhesion and the
      desquamation of cells from the underlying lamina propria allows malignant cells
      to escape from their site of origin, degrade the extracellular matrix, acquire a
      more motile and invasive phenotype, and finally invade and metastasize. In
      addition to participating in tumor invasiveness and metastasis, adhesion
      molecules regulate or significantly contribute to a variety of functions,
      including signal transduction, cell growth, differentiation, site-specific gene
      expression, morphogenesis, immunologic function, cell motility, wound healing,
      and inflammation. To date, a diverse system of transmembrane glycoproteins have
      been identified that mediate the cell-cell and the cell-extracellular matrix
      adhesion. The main families of adhesion molecules are the cadherins, integrins,
      members of the immunoglobulin superfamily, and selectins. We review the recent
      data regarding the role of selected adhesion molecules in the pathogenesis of
      bladder cancer and their clinical exploitation as biomarkers of this malignant
      disease.

PMID- 9933074
TI  - Possible mechanisms for epididymal sparing during testicular ischemia.
AB  - OBJECTIVES: Although extensive research has been conducted on the normal anatomy
      and physiology of the epididymis, the effects of ischemia on the organ have not
      been primarily investigated. The aim of the present study was to investigate the
      macroscopic and microscopic effects of prolonged ischemia on the epididymis and
      the factors that may contribute to its resistance to ischemia. METHODS: Six
      groups of male Sprague-Dawley rats (6 rats/group) were studied. Groups 1, 2, and
      3 underwent a sham operation of 4, 8, and 12 hours, respectively, and groups 4,
      5, and 6 underwent 4, 8, and 12 hours of ischemia, respectively. The ipsilateral
      testes and epididymides were monitored throughout the experiment. At the
      conclusion of the experiment, bilateral orchiectomy was performed, and structures
      were histologically evaluated. RESULTS: There were no abnormal macroscopic
      findings of the bilateral epididymides of groups 1, 2, and 3 or of the
      contralateral, control epididymides of groups 4, 5, and 6. Macroscopically, there
      was a direct correlation between the length of ischemia and the degree of
      hemorrhagic discoloration of the proximal caput. The degree of hemorrhagic
      infiltration noted microscopically was consistent with the macroscopic
      observations. The epithelia of the ischemic epididymides remained intact with
      numerous microvilli. CONCLUSIONS: The results of this study suggest that the
      epithelium of the epididymis is relatively resistant to ischemic damage compared
      with the gonad during testicular ischemia.

PMID- 9933075
TI  - Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude
      mouse xenograft model by increasing apoptosis.
AB  - OBJECTIVES: Recent studies have shown that Exisulind, a sulfone metabolite of the
      nonsteroidal anti-inflammatory drug (NSAID) sulindac, has inhibitory activity in
      vitro with cultured human prostate cancer cells. To determine whether this effect
      might be pharmacologically relevant in vivo, we tested whether Exisulind therapy
      could suppress the growth of human prostate cancer cells in a nude mouse
      xenograft model. METHODS: Thirty athymic nude mice were injected subcutaneously
      in the flank with 1 x 10(7) LNCaP human prostate tumor cells. All mice received a
      control diet for 21 days. One group of mice was continued on this control diet
      for an additional 4 weeks, a second group was switched to a diet supplemented
      with 0.05% Exisulind (40% of maximal tolerated dose [MTD]), and a third group was
      switched to a diet supplemented with 0.1% Exisulind (80% MTD) for the additional
      4 weeks. Tumor growth was measured through the 4-week test period, and
      subsequently tissue sections from the various groups were tested for apoptotic
      and dividing cells by quantified use of the TUNEL assay and a bromodeoxyuridine
      (BrdU) incorporation immunoassay. RESULTS: Tumors grew by 158%, 24%, and 18% for
      the control and 0.05% and 0.1% Exisulind groups, respectively (P = 0.02) during
      the 4-week test period. Immunohistochemical studies on excised tumors showed an
      increased number of apoptotic bodies in the treated groups versus the control
      group (P<0.0001) but no change in the number of BrdU positive cells. CONCLUSIONS:
      This is the first study to show a direct in vivo effect of an NSAID-derived drug,
      lacking cyclooxygenase inhibitory activity, in a xenograft model of prostate
      cancer. Clinical studies to evaluate the effects of Exisulind against prostate
      cancer in humans are warranted.

PMID- 9933076
TI  - Biochemical evaluation of obstructive bladder dysfunction in men secondary to
      BPH: a preliminary report.
AB  - OBJECTIVES: In the rabbit, two of the major cellular alterations that mediate
      bladder dysfunction secondary to partial outlet obstruction are a decreased
      ability of the sarcoplasmic reticulum (SR) to store and release Ca2+, and
      mitochondrial dysfunction. The objective of the current study was to determine
      whether SR and mitochondrial dysfunctions are associated with symptomatic benign
      prostatic hyperplasia (BPH) in men. METHODS: Bladder biopsies were obtained from
      men with symptomatic BPH and from age-matched men with no urologic dysfunction.
      Each biopsy was analyzed for the following enzyme activities: malate
      dehydrogenase and citrate synthase (mitochondrial markers) and the sarcoplasmic
      reticular enzyme Ca2+ -dependent adenosine triphosphatase (ATPase). These values
      were compared with the enzyme activities of control rabbit bladder smooth muscle
      and bladder smooth muscle obtained from rabbits subjected to 2 weeks of partial
      outlet obstruction. RESULTS: The enzymatic activities of all three enzymes are
      significantly lower in human bladder smooth muscle than in rabbit bladder smooth
      muscle. The maximal activities of all three enzymes are significantly lower in
      human bladder samples obtained from men with diagnosed obstructive uropathy than
      in men of equal age with no urologic dysfunction. CONCLUSIONS: These studies
      demonstrate that similar to the response of the rabbit to partial outlet
      obstruction, obstructive dysfunction secondary to BPH is characterized by
      mitochondrial and SR dysfunction.

PMID- 9933077
TI  - Pneumoperitoneum does not potentiate the nephrotoxicity of aminoglycosides in
      rats.
AB  - OBJECTIVES: Pneumoperitoneum is associated with transient renal dysfunction. To
      our knowledge, the safety of administering nephrotoxins such as aminoglycosides
      during pneumoperitoneum has not been studied. Our hypothesis was that
      pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides. METHODS: From
      29 rats we obtained preprocedure 24-hour urine collections. In the
      pneumoperitoneum group (n = 7), carbon dioxide was insufflated intra-abdominally
      at 15 mm Hg pressure for 2 hours. In the gentamicin group (n = 7), 10 mg/kg
      gentamicin was administered intravenously. In the combined
      pneumoperitoneum/gentamicin group (n = 8), the same dose of gentamicin was
      administered 10 minutes before pneumoperitoneum. Sham rats (n = 7) received
      anesthesia only. Urine was collected for the 24 hours after the procedure, and 1
      week later blood for creatinine determination and final 24-hour urine collections
      were obtained. All urine samples were assayed for creatinine and N-acetyl-beta
      glucosaminidase (NAG). RESULTS: Only the gentamicin and combined
      pneumoperitoneum/gentamicin groups presented day 1 values for NAG excretion that
      were significantly greater than same day sham or paired preprocedure values; the
      rest of the urinary creatinine and NAG day 1 levels and all the day 7 levels were
      not significantly different from same day sham or paired preprocedure levels. Day
      7 serum creatinine and creatinine clearance did not differ significantly among
      the groups. CONCLUSIONS: We found that intravenous gentamicin transiently
      increased urinary excretion of NAG in rats, which resolved within 1 week.
      Pneumoperitoneum for 2 hours at 15 mm Hg did not increase urinary NAG, either
      alone or in gentamicin-treated rats. Moreover, our data are sufficient to refute
      with 95% certainty the possibility that gentamicin plus pneumoperitoneum
      decreases creatinine clearance more than approximately 60%. These results do not
      support the hypothesis that pneumoperitoneum potentiates the nephrotoxicity of
      aminoglycosides.

PMID- 9933078
TI  - Malpractice risks for urologists.

PMID- 9933079
TI  - Testicular microlithiasis and carcinoma in situ.

PMID- 9933080
TI  - IL-12 directs severe renal injury, crescent formation and Th1 responses in murine
      glomerulonephritis.
AB  - Glomerular crescent formation characterizes severe glomerulonephritis (GN).
      Evidence suggests that crescent formation results from a delayed-type
      hypersensitivity-like Th1 response. As IL-12 directs Th1 responses, we tested the
      hypothesis that IL-12 is important in crescentic GN. Neutralization of IL-12
      attenuated crescent formation and cell-mediated injury in C57BL/6 mice sensitized
      to and challenged with sheep anti-mouse glomerular basement membrane (GBM)
      globulin. Recombinant IL-12 induced severe crescentic GN with enhanced Th1
      responses in C57BL/6 mice in which non-crescentic GN was induced by injecting
      anti-GBM globulin into naive mice. BALB/c mice do not develop significant
      crescent formation in these models, due either to regulatory effects of IL-4, or
      to deficits in IL-12 production/responsiveness. Administering IL-12 to BALB/c
      mice with GN induced Th1 responses and crescent formation, whereas IL-4-deficient
      BALB/c mice did not develop cell-mediated crescentic injury when GN was induced
      in sensitized mice. These results establish a central role for IL-12 in severe
      crescentic GN.

PMID- 9933081
TI  - Regulation of cytokine expression and leukotriene formation in human basophils by
      growth factors, chemokines and chemotactic agonists.
AB  - Basophils stimulated with IL-3 plus C5a selectively express IL-4 and IL-13 and
      continuously produce leukotrienes (LT) for hours. C5a combined with IL-5 or
      granulocyte-macrophage colony-stimulated factor was, however, much less effective
      in promoting cytokine expression and a late continuous phase of LTC4 production,
      possibly due to lower expression levels of their receptor alpha chains. Basophils
      also express several chemoattractant receptors, including high levels of C5a
      receptors, macrophage chemotactic protein (MCP) receptors (CCR2) and eotaxin
      receptors (CCR3), intermediate levels of CXCR1, CXCR2 and platelet-activating
      factor receptors, and lower levels of N-formyl-Met-Leu-Phe (fMLP) receptors.
      However, among the corresponding agonists, only C5a, fMLP and much more weakly
      MCP1, were found to induce cytokine expression and continuous LTC4 release, and
      only when combined with IL-3. CCR3, which is highly expressed on basophils and
      has been shown to mediate strong migratory but weak release responses, does not
      regulate cytokine expression. The weakly expressed fMLP receptor is an efficient
      activator of several cell functions including LTC4 formation, while CXCR2 hardly
      affects basophil function despite considerable expression. Thus, chemoattractant
      receptors mediate different cellular responses unrelated to their expression
      levels.

PMID- 9933082
TI  - Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory
      receptors in human T lymphocytes.
AB  - Different HLA class I-specific killer inhibitory receptors (KIR) are expressed in
      vivo by a fraction of activated T cells, predominantly CD8+, in which they may
      inhibit TCR-mediated cell functions. In an attempt to identify mechanisms leading
      to KIR expression in T cells, we analyzed the effect of transforming growth
      factor-beta (TGF-beta) in T cells responding to bacterial superantigens in vitro.
      We show that TGF-beta induces the expression of CD94/NKG2A in cells responding to
      toxic shock syndrome toxin 1 or to other staphylococcal superantigens.
      Remarkably, maximal CD94 expression occurred at (low) TGF-beta concentrations
      which have no substantial effect on lymphocyte proliferation. Maximal CD94
      expression occurred when TGF-beta was added shortly after the cells were placed
      in culture. No expression could be induced in CD94/NKG2A-negative T cell clones.
      Although both CD4+ and CD8+ expressed CD94, the simultaneous expression of NKG2A
      was mostly confined to CD8+ cells. Monoclonal antibody-mediated cross-linking of
      CD94/NKG2A led to an impairment of T cell triggering via CD3, as determined in a
      redirected killing assay using the Fcgamma receptor-positive P815 murine target
      cells.

PMID- 9933083
TI  - Cellular requirements for the monoclonal antibody-mediated eradication of an
      established solid tumor.
AB  - Following subcutaneous implantation, the murine lymphoma E.G7 [a variant of EL-4,
      transfected with the chicken ovalbumin (OVA) gene] up-regulates the CD4 molecule.
      We previously showed that the administration of an anti-CD4 monoclonal antibody
      (mAb) to EG.7-bearing mice leads to a rapid and complete regression of large
      established tumors. This tumor regression was shown to require both CD8+ cells
      and functional Fcgamma receptors (FcgammaR), as it failed to occur in mice
      depleted of CD8 cells, or mice genetically deficient in FcgammaI/III (gamma-/
      mice). Using adoptive transfer, we now show that the FcgammaR+ cells required for
      this regression are the CD11b+ (phagocytic) cells. Furthermore, experiments using
      peptide tolerization demonstrated that the critical CD8 CTL population in this
      model is tumor specific. Analysis of tumors at various stages of regression
      revealed a massive CD11b+FcgammaR+ and a marginal CD8 infiltration. In the
      presence of the CTL determinant OVA-8 on tumor cells and of the antitumor mAb,
      this CD8 infiltration became remarkable, and correlated with tumor regression.
      These results identify the specific cellular effectors essential for the mAb
      mediated tumor regression, and suggest that FcgammaR-activated macrophages
      induced an expansion of tumor-eliminating CTL in situ.

PMID- 9933084
TI  - Altered ex vivo balance between CD28+ and CD28- cells within HIV-specific CD8+ T
      cells of HIV-seropositive patients.
AB  - The CD8+CD28- cell population in the blood of HIV-infected individuals is
      considerably expanded. Yet the cause of this expansion is not clear. The recent
      demonstration of identical TCR-rearranged genes in CD8+CD28+ and CD8+CD28-
      expanded T cells of HIV-seropositive patients supports the hypothesis that these
      two subpopulations are phenotypic variants of the same lineage. To further
      elucidate the precise relationship between them, we measured the fraction of
      CD28+ and CD28- T cell subsets in IFN-gamma-producing CD8+ T cells by
      intracellular staining and cytofluorometry as a functional test for ex vivo
      recognition of epitopes derived from HIV-1, Epstein-Barr virus (EBV) and
      influenza virus. HIV-specific CD8+ T cells were predominantly CD28 in all the
      eight HIV-seropositive subjects tested. In contrast, the anti-EBV and anti
      influenza CD8+ T cells were mainly CD28+ in these patients as well as in HIV
      seronegative individuals. This supports the notion that the CD8 CD28
      hyperlymphocytosis observed in HIV infection is due mainly to chronic activation
      and differentiation of HIV-specific memory CD8+CD28+ T cells into terminally
      differentiated CD8+CD28-lymphocytes, because of intense HIV-1 replication and
      without any important bystander activation. This clarification of the mechanisms
      underlying the CD8+CD28- expansion in HIV-induced pathogenesis may have important
      therapeutic implications.

PMID- 9933085
TI  - ICAM-1 and B7-1 provide similar but distinct costimulation for CD8+ T cells,
      while CD4+ T cells are poorly costimulated by ICAM-1.
AB  - The function of purified ICAM-1 in costimulating CD4+ and CD8+ T cell responses
      has been directly compared to that of B7-1 in a model system that minimizes
      contributions of other receptor-ligand interactions. While B7-1 costimulates both
      subsets of T cells, ICAM-1 is much more effective in the costimulation of CD8+
      cells. ICAM-1 also synergizes with B7-1 for the induction of IL-2 production in
      CD8+ but not CD4+ T cells. These differences are not explained by differences in
      LFA-1 receptor expression on the two subsets of T cells. The CD8+ T cell response
      to ICAM-1 costimulation is associated with increased proliferation and IL-2
      production at levels similar to those seen with B7-1 costimulation, but clonal
      expansion in response to ICAM-1 is not as great due to decreased cell survival.
      ICAM-1-mediated costimulation is effective for both naive and memory CT8+ T
      cells, is independent of CD28 engagement, and does not appear to be due solely to
      effects on adhesion. These results suggest that ICAM-1-dependent, B7-independent
      costimulation may be important in initiating a CTL response to class I antigen
      presented by cells that are not professional APC.

PMID- 9933086
TI  - Involvement of autoimmunity against type II collagen in the development of
      arthritis in mice transgenic for the human T cell leukemia virus type I tax gene.
AB  - We previously reported that transgenic mice carrying the human T cell leukemia
      virus type I (HTLV-I) env-pX region (pX-transgenic mice) develop rheumatoid-like
      inflammatory arthropathy, and suggested involvement of autoimmunity in the
      pathogenicity. In this report, to elucidate pathogenesis of the arthritis, we
      investigated arthritogenic antigens in the joints. The TCR beta-chain variable
      region (Vbeta) repertoires in the lymphatic organs were normal in transgenic
      mice, however, specific Vbeta-positive T cells were expanded oligoclonally in the
      affected joints, suggesting that specific antigens, but not superantigens, were
      involved in the expansion of these T cells. These expanded T cells had the same
      TCR as those of lymph node T cells reactive to type II collagen (IIC). Moreover,
      these mice were susceptible to IIC-induced arthritis and oligoclonal T cells of
      the same Vbeta specificity as that found in spontaneously developed arthritic
      joint accumulated in the arthritic joints after immunization with IIC. These
      observations show that endogenous IIC is one of the arthritogenic antigens in the
      joint, suggesting tolerance break to this antigen in pX-transgenic mice.

PMID- 9933087
TI  - CD20 is physically and functionally coupled to MHC class II and CD40 on human B
      cell lines.
AB  - Engagement of MHC class II and CD40 on B cell lines triggers intracellular
      signals that activates cell surface adhesion receptors, resulting in LFA-1
      dependent and -independent cell-cell adhesion. In this study, a murine monoclonal
      antibody (mAb R21) has been produced against a LFA-1-negative human B cell line
      and proven to completely block MHC class II- and CD40-induced LFA-1-independent
      homotypic adhesion. However, this mAb failed to prevent MHC class II- or CD40
      induced homotypic adhesion in LFA-1-positive Raji B cells, and alone, it
      triggered LFA-1-dependent cell-cell adhesion. Biochemical characterization
      indicated that the CD20 molecule, a tetraspan phosphoprotein expressed on B cells
      that functions as a Ca2+-conductive ion channel, is the target of mAb R21.
      Interestingly, further biochemical analysis demonstrated that CD20 is physically
      associated with MHC class II and CD40 molecules on the cell surface of LFA-1
      negative and LFA-1-positive B cell lines. Although these three molecules are
      associated with each other, the complex formation between any two of them is not
      dependent on the simultaneous expression of the three molecules. Altogether,
      these results indicate that CD20 is physically and probably functionally coupled
      to the MHC class II and CD40 molecules; thereby it may have certain modulatory
      effects on their functions.

PMID- 9933088
TI  - Studies on the phenotype of migrant thymic stem cells.
AB  - Stem cells first enter the thymus around the 11th to 12th days of gestation in
      BALB/c mouse embryos. The phenotype of these stem cells has been difficult to
      determine because their entry occurs when the thymic primordium is very small and
      involves too few stem cells to allow studies by flow cytometry. We have been able
      to microdissect the thymus from embryos during this stage and immunophenotype
      cells in sections using a sensitive tyramide amplification system. Our results
      show that migrant stem cells express CD45, c-kit, CD44, CD34 and alpha4 integrin,
      but other markers such as CD62L, CD25, Thy-1.2, CD3epsilon, alpha5 integrin and
      RAG-1 expression are detected only after stem cell entry. These results should
      help to improve the isolation and characterization of migrant thymic stem cells.

PMID- 9933089
TI  - Increased susceptibility of Fas ligand-deficient gld mice to Trypanosoma cruzi
      infection due to a Th2-biased host immune response.
AB  - Infection of BALB/c mice with Trypanosoma cruzi resulted in up-regulated
      expression of Fas and Fas ligand (FasL) mRNA by splenic CD4+ T cells, activation
      induced CD4+ T cell death (AICD), and in Fas: FasL-mediated cytotoxicity. When
      CD4+ T cells from infected mice were co-cultured with T. cruzi-infected
      macrophages, onset of AICD exacerbated parasite replication. CD4+ T cells from T.
      cruzi-infected FasL-deficient BALB gld/gld mice had no detectable AICD in vitro
      and their activation with anti-TCR did not exacerbate T. cruzi replication in
      macrophages. However, infection of BALB gld/gld mice with T. cruzi resulted in
      higher and more prolonged parasitemia, compared to wild-type mice. Secretion of
      Th2 cytokines IL-10 and IL-4 by CD4+ T cells from infected gld mice was markedly
      increased, compared to controls. In addition, in vivo injection of anti-IL-4 mAb,
      but not of an isotype control mAb, reduced parasitemia in both gld and wild-type
      mice. These results indicate that, besides controlling CD4+ T cell AICD and
      parasite replication in vitro, an intact Fas: FasL pathway also controls the host
      cytokine response to T. cruzi infection in vivo, being required to prevent an
      exacerbated Th2-type immune response to the parasite.

PMID- 9933090
TI  - Regulation by cytokines (IL-12, IL-15, IL-4 and IL-10) of the Vgamma9Vdelta2 T
      cell response to mycobacterial phosphoantigens in responder and anergic HIV
      infected persons.
AB  - Human Vgamma9Vdelta2 T cells contribute to immunity against intracellular
      pathogens and recognize nonpeptidic antigens, such as the mycobacterial
      phosphoantigen TUBAg. HIV infection is associated with a polyclonal decrease of
      peripheral Vgamma9Vdelta2 T cells and we previously reported that the remaining
      cells show a proliferative anergy to stimulation with Mycobacterium tuberculosis
      in 60% of patients. Because of alterations in the Th1/Th2 cytokine balance
      reported in HIV infection, we analyzed, at the single-cell level, the influence
      of exogenous IL-4, IL-10, IL-12 and IL-15 on the response to mycobacterial
      phosphoantigens of gammadelta T cells from HIV-infected patients and healthy
      donors. We report that the strong gammadelta T cell response to TUBAg is
      characterized by the rapid and selective production of the Th1/proinflammatory
      cytokines IFN-gamma and TNF-alpha in responder HIV-infected donors. In addition,
      a positive regulation by IL-12 and IL-15 of the production of these cytokines by
      Vgamma9Vdelta2 T cells in response to nonpeptidic ligands was observed, whereas
      IL-4 and IL-10 had no effect. In contrast, Vgamma9Vdelta2 T cells from the
      anergic HIV-infected donors had lost the ability to produce Th1 cytokines and
      were not shifted towards a Th2 profile. Furthermore, neither IL-12 nor IL-15
      could reverse this functional anergy. The consequences of these observations are
      discussed in the context of HIV pathogenesis.

PMID- 9933091
TI  - Transforming growth factor-beta isoforms regulate the surface expression of
      membrane cofactor protein (CD46) and CD59 on human keratinocytes [corrected].
AB  - We studied the regulation of the expression of complement regulatory proteins,
      membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, on
      human keratinocytes by supernatant of activated mononuclear cells and by some
      individual cytokines present therein. Cultured keratinocytes expressed MCP, DAF
      and CD59. Supernatant of activated mononuclear cells and recombinant forms of
      transforming growth factor (TGF)-beta variants (beta1, beta2 and beta3) up
      regulated MCP and CD59 but not DAF. Recombinant IL-1alpha, IL-2, IL-6, TNF-alpha
      and IFN-gamma had no influence. TGF-beta present in the supernatant was likely
      responsible for up-regulation of MCP and CD59. A monoclonal anti-TGF-beta
      antibody, which neutralized TGF-beta1, -beta2 and -beta3, did not inhibit the up
      regulation of MCP and CD59 by the supernatant. These results indicated that TGF
      beta and an additional factor(s) present in the supernatant may be responsible
      for up-regulating the expression of MCP and CD59 on keratinocytes; both may be
      acting non-synergistically.

PMID- 9933092
TI  - Neonatal colonization of rats induces immunological tolerance to bacterial
      antigens.
AB  - We wanted to investigate the immunological events occurring in rats intestinally
      colonized from birth (neonatally) or at adult age with an ovalbumin (OVA)
      producing Escherichia coli O6K13 strain, carrying type 1 pili. The neonatally
      colonized animals responded with lower delayed type hypersensitivity (DTH)
      against OVA and lower levels of IgG antibodies against OVA, O6 lipopolysaccharide
      (LPS) and type 1 pili compared to age-matched controls. The IgG antibody response
      against the bystander antigen, human serum albumin (HSA), was lower in the
      neonatally colonized animals than in the controls co-immunized with HSA and E.
      coli, indicating a release of suppressive factors induced by the bacterial
      antigens. The adult colonized animals showed an increased DTH and antibody
      response against OVA after immunization. They also had high pre-immunization
      levels of IgG anti-O6 LPS antibodies compared to controls. However, the relative
      increase in IgG anti-O6 LPS antibody levels after the immunization with dead E.
      coli was much lower in the adult colonized animals. The present results suggest
      that neonatal animals develop tolerance against antigen on bacterial colonizers
      of the intestine. In addition, this tolerance contains components of suppression.

PMID- 9933093
TI  - Endogenous and exogenous forms of the same antigen are processed from different
      pools to bind MHC class II molecules in endocytic compartments.
AB  - The current studies were carried out to examine the basis for the differences in
      the antigenic peptides generated from exogenous and endogenous forms of hen egg
      white lysozyme (HEL). The role of different intracellular compartments in the
      generation and binding of HEL peptides derived from two endogenous forms of HEL,
      either secreted (sHEL) or retained in the endoplasmic reticulum (ER, KDELHEL),
      presented by MHC class II molecules was examined and compared to exogenous HEL.
      Initially it was found that antigen-presenting cells bearing both intracellular
      forms of HEL generated and presented a number of IAk-restricted HEL epitopes to T
      cell hybridomas, although sHEL was processed more efficiently than KDEL-HEL.
      There were differences, however, for some determinants between endogenous and
      exogenous HEL. At equivalent antigen-presenting efficiencies, endogenous HEL
      bearing cells displayed a lower surface density of IAk-bound HEL-52-61-related
      peptides than cells pulsed with exogenous HEL, as detected by a specific
      monoclonal antibody. Neither endogenous HEL degradation nor peptide binding to
      MHC class II molecules occurred in the ER. Processing of sHEL and KDELHEL appears
      to take place either in a post-trans-Golgi network acidic compartment or in the
      cytosol, whereas peptide binding to MHC class II molecules occurs in endocytic
      compartments. Furthermore, the peptides generated were derived from an endogenous
      source rather than from secreted and re-endocytosed HEL. Thus, processing of
      endogenous HEL is from a different pool than exogenous HEL and occurs in
      different compartments.

PMID- 9933095
TI  - The alternatively spliced CD64 transcript FcgammaRIb2 does not specify a surface
      expressed isoform.
AB  - Three highly homologous genes (A, B and C) and six transcripts have been
      identified for the class I human IgG receptor (CD64). The hFcgammaRIa1 isoform
      encodes the prototypic high-affinity receptor for IgG. The alternatively spliced
      hFcgammaRIb2 transcript was postulated to exist as a second surface-expressed
      CD64 isoform on myeloid cells. In this report we assessed this proposed role for
      hFcgammaRIb2 in detail. As CD64 monoclonal antibodies might not recognize
      hFcgammaRIb2, we tagged the receptor with an hemagglutinin tag and transfected
      hFcgammaRIb2tag in the presence of FcR gamma-chain into IIA1.6 cells. Both
      transcript and protein of hFcgammaRIb2tag were clearly present in transfectants.
      However, in contrast to the (control) hFcgammaRIa1tag, no surface expression of
      hFcgammaRIb2tag was detectable with a tag-specific monoclonal antibody. Confocal
      scan laser microscopy revealed hFcgammaRIb2tag to be retained in the endoplasmic
      reticulum, resulting in absent plasma membrane expression. These results show
      hFcgammaRIb2 neither to be surface expressed, nor to represent a separate CD64
      isoform. This finding, furthermore, implicates that other FcR transcripts defined
      at the mRNA level may not represent true FcR isoforms either.

PMID- 9933094
TI  - Protein kinase Ctheta, a selective upstream regulator of JNK/SAPK and IL-2
      promoter activation in Jurkat T cells.
AB  - The predominant expression of protein kinase C (PKC) theta in T cells (J. Biol.
      Chem. 1993. 268: 4997-5004), its isoenzyme-specific ability to stimulate AP-1
      transcriptional activity (Mol. Cell. Biol. 1996. 16: 1842-1850) and the recent
      discovery of its selective and antigen-dependent colocalization with the contact
      region between T cells and antigen-presenting cells (Nature 1997. 385: 83-89)
      suggest that, among the PKC family members, PKCtheta plays a specialized role in
      T cell activation. By investigating the downstream effectors of PKCtheta we now
      demonstrate a direct and isoenzyme-specific contribution of PKCtheta to c-Jun-N
      terminal kinase/stress-activated protein kinase (JNK/SAPK) but not extracellular
      regulated kinase (ERK) activation. Expression of a constitutively active (CA)
      form of PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) resulted in
      strong activation of JNK/SAPK and expression of a dominant-negative form of
      PKCtheta interfered with the endogenous activation signal for JNK/SAPK.
      Importantly, Ca2+ ionophore and CA-PKCtheta (but not CA-PKCalpha, epsilon and
      lambda/iota) caused synergistic activation of the IL-2 promoter. Together, these
      data establish that PKCtheta is required for activation of JNK/SAPK signaling
      leading to IL-2 promoter transcription in T lymphocytes.

PMID- 9933096
TI  - Analysis of peripheral immune tolerance uncovers a mouse strain-dependent in situ
      type of graft tolerance.
AB  - We screened various mouse strains [C57BL/6, BALB/c, DBA/2, CBA/Ca,
      (CBAxC57L/6)F1, SJL, C3H] for induction of peripheral immune tolerance. Only
      CBA/Ca mice treated with anti-CD4 + CD8 monoclonal antibodies and grafted with
      allogeneic skin showed long-term graft survival (150 to >200 days).
      Interestingly, T cells from the tolerant CBA/Ca mice rejected bone marrow/spleen
      cells of the skin graft donor strain and caused lethal graft-versus-host disease
      when transplanted to the donor strain. Furthermore, peripheral tolerance was
      easily broken: CBA/Ca mice could be reactivated to reject their tolerated grafts
      via immunization with (graft donor x recipient strain)F1 bone marrow cells. Thus,
      in contrast to the generalized nature of central tolerance, our experiments show
      that peripheral immune tolerance is strain dependent and locally restricted to
      graft tissue.

PMID- 9933097
TI  - CD4 T cells can reject major histocompatibility complex class I-incompatible skin
      grafts.
AB  - We have re-investigated the roles of CD4 and CD8 T cell subsets in skin graft
      rejection across a single class I MHC disparity. Recipient mice were transplanted
      with skin from donors transgenic for the class I MHC molecule Kb. As expected,
      CD8 T cells were sufficient for rapid injection; but surprisingly, CD4 T cells
      were also competent to do the same. Rejection was dependent on one or the other
      subset, since elimination of both resulted in indefinite graft survival. The
      possibility that alloantibody was the downstream effector of CD4 mediated
      rejection was excluded because CD8-depleted mice rendered B cell deficient still
      rejected rapidly, but T cell-depleted recipients with pre-existing high titers of
      alloantibody were unable to do so. In addition, if CD4 cells act to reject by
      recruiting and/or activating macrophages then this was not dependent on CR3, IFN
      gamma or TNF-alpha. Transplantation of skin grafts where the MHC class I
      disparity was at the level of passenger leukocytes only, demonstrated that
      transient bystander damage could occur, but that this was insufficient to result
      in full rejection. We surmise that for CD4 T cells to reject an MHC class I
      incompatible graft it is necessary that an appropriate allogeneic peptide is
      processed and presented in the context of recipient MHC class II. CD4 T cells
      from B6 mice may fail to reject skin from MHC class I mutants because of the lack
      of such MHC class II-restricted presentation.

PMID- 9933098
TI  - Different regulatory pathways employed in cytokine-enhanced expression of
      secretory component and epithelial HLA class I genes.
AB  - The transmembrane secretory component (SC, or pIg receptor) plays a crucial role
      in mucosal immunity by translocating dimeric IgA and pentameric IgM through
      exocrine epithelia. This receptor is up-regulated by cytokines in parallel with
      increased epithelial HLA expression. By use of the human epithelial cell line HT
      29m3, we show that IFN-gamma, TNF-alpha and IL-4 activate transcription of the SC
      gene. This activation was slow, suggesting mediation via newly synthesized
      protein factors. IFN-gamma and TNF-alpha, but not IL-4, also up-regulated
      expression of HLA class I genes. However, this gene induction was rapid and did
      not depend on new protein synthesis. Nuclear run-on experiments showed that the
      transcription rate of HLA class I genes nearly peaked after only 30 min of IFN
      gamma or TNF-alpha stimulation, whereas the SC transcription rate did not peak
      until after 20-36 h of IFN-gamma, TNF-alpha or IL-4 stimulation. Gel
      electrophoresis mobility shift assays demonstrated binding of nuclear proteins
      from cytokine-stimulated HT-29 cells to consensus elements in the promoter of the
      SC gene, involving the binding site for the nuclear factor-kappaB p50 subunit
      after TNF-alpha stimulation, and IFN-stimulated response element after IFN-gamma
      stimulation (and weakly after TNF-alpha. Our observations in vitro likely
      parallel events in vivo by which activated mucosal T cells and macrophages
      enhance pIg receptor-mediated external transport of secretory IgA and IgM and up
      regulate epithelial HLA expression.

PMID- 9933099
TI  - Classical MHC class I peptide presentation of a bacterial fusion protein by bone
      marrow-derived dendritic cells.
AB  - Dendritic cells (DC) expanded in the presence of GM-CSF from the bone marrow of
      C57BL/6 mice process Gram-negative bacteria expressing the model antigen Crl-OVA
      for peptide presentation on MHC class I molecules. Here we show that presentation
      of OVA(257-264) processed by DC co-incubated with E. coli expressing Crl-OVA,
      which contains the Kb-binding OVA(257-264) epitope, occurs by a cytosolic MHC-I
      presentation pathway. First, we demonstrate the requirement for the transporter
      associated with antigen processing (TAP) by showing that DC from TAP1-/- mice co
      incubated with E. coli expressing Crl-OVA did not result in Kb presentation of
      OVA(257-264). Second, the proteasome inhibitor MG132 abrogated presentation of
      OVA(257-264) on Kb when C57BL/6 DC phagocytosed and processed E. coli expressing
      Crl-OVA. Third, inhibiting protein synthesis using cycloheximide or blocking
      exocytosis of newly synthesized proteins from the endoplasmic reticulum using
      brefeldin A abrogated presentation of OVA(257-264) processed from bacteria
      expressing Crl-OVA by C57BL/6 DC. Finally, peptide regurgitation and loading of
      OVA(257-264) on neighboring bystander Kb-expressing antigen-presenting cells
      after BALB/c (H-2d) DC phagocytosed E. coli expressing Crl-OVA could not be
      detected. Together, these data support a cytosolic MHC-I presentation pathway for
      OVA(257-264) processed from E. coli expressing Crl-OVA by bone marrow-derived DC.

PMID- 9933100
TI  - N-terminal elongation of a peptide determinant beyond the first primary anchor
      improves binding to H-2 I-Ad and HLA-DR1 by backbone-dependent and aromatic side
      chain-dependent interactions, respectively.
AB  - The IgG2a(b) heavy chain allopeptide determinant gamma2a(b) 436-451 (Kabat
      numbering) presented by the major histocompatibility complex (MHC) class II
      molecule I-Ad is recognized by T cells which cross-react with a corneal self
      antigen and with the UL6 protein of the herpes simplex virus which induce
      autoimmune keratitis, and is the target of Th1 clones that suppress IgG2a(b)
      production in vivo. In the gamma2a(b) peptide/l-Ad complex, tyrosine438 is the
      first primary anchor (P1) and residues 440-445 encompass the T cell receptor
      contact residues. Amino-terminal elongation of gamma2a(b) 437-451 by a single
      residue (P-2) augmented the I-Ad binding capacity 10-fold and the antigenicity 55
      195-fold. This was a function of the peptide main chain, since non-conservative
      substitutions were accepted. The gamma2a(b) peptide also bound HLA-DR1, and amino
      terminal extension by a single aromatic amino acid at P-3 augmented binding 15
      fold. The interaction between HLA-DR1 and P-3 specifically required an aromatic
      peptide side chain, and computer simulations indicated that the aromatic ring at
      P-3 engaged conserved HLA-DR1 phenylalanine residues at the edge of the peptide
      binding groove. Thus, these data demonstrate that residues amino terminal to P1
      may substantially increase peptide affinity for MHC class II by main chain
      dependent as well as side chain-dependent interactions, and imply that the HLA
      DR1 motif should be extended to include an aromatic amino acid at P-3.

PMID- 9933101
TI  - Dendritic cells transfected with the nef genes of HIV-1 primary isolates
      specifically activate cytotoxic T lymphocytes from seropositive subjects.
AB  - The HIV-1 Nef protein down-modulates surface expression of MHC class I proteins.
      Primary infected T lymphocytes thus escape lysis by cytotoxic T lymphocytes
      (CTL). In contrast, during HIV-1 infection there are strong CTL responses to
      several HIV proteins, and there is mounting evidence that CTL are critical for
      controlling the virus. The present study was carried out to assess Nef protein
      cell interaction as it occurs in naturally infected antigen-presenting cells. To
      evaluate the presentation of peptides derived from viral antigen to CTL, we
      transfected nef genes obtained from peripheral blood mononuclear cells of HIV-1
      seropositive subjects into dendritic cells isolated from monocytes of healthy
      donors. We demonstrate that expression and subsequent processing of Nef by
      transfected dendritic cells did not alter the presentation of an immunodominant
      epitope of Nef to CTL of HIV+ subjects. However, mutations in nef gene sequences
      from primary isolates may abolish this presentation by a mechanism that probably
      interferes with protein processing.

PMID- 9933102
TI  - Leishmania donovani infection initiates T cell-independent chemokine responses,
      which are subsequently amplified in a T cell-dependent manner.
AB  - Control of Leishmania donovani infection in immunocompetent mice is associated
      with hepatic inflammation and granuloma formation, both of which are absent in
      severe combined immunodeficient (scid) mice. In both BALB/c and scid mice, L.
      donovani infection induced a rapid hepatic accumulation of mRNA encoding
      macrophage inflammatory protein-1alpha (MIP-(1alpha), monocyte chemoattractant
      protein-1 (MCP-1) and interferon-gamma inducible protein-10 (gammaIP-10). This
      response was not preceded by increased IL-4 production in either strain, unlike
      that reported in other infectious disease models. Interestingly, only gammaIP-10
      mRNA was maintained at elevated levels throughout the first 7 days of infection,
      by mechanisms involving CD4+ and CD8+ T cells, and CD4+CD8+ cells not activated
      in scid mice. By in vivo depletion and reconstitution of scid mice it was
      demonstrated that T cells regulate the expression of all three chemokines
      studied, while they themselves only produce gammaIP-10 in appreciable quantities.

PMID- 9933103
TI  - Expression of multiple forms of IL-1 receptor antagonist (IL-1ra) by human
      retinal pigment epithelial cells: identification of a new IL-1ra exon.
AB  - The eye is considered an immunologically privileged organ and is separated from
      the rest of the body by blood-ocular barriers. Part of the blood-retina barrier
      consists of the retinal pigment epithelium (RPE). In addition to the physical
      barrier which the monolayer of RPE cells forms, these cells contribute to ocular
      immune privilege by producing anti-inflammatory molecules that down-regulate
      potential damaging immune reactions. In this study the mRNA expression of IL-1
      receptor antagonist (IL-1ra) by RPE cells was studied in 15 donor-derived cell
      lines. Expression of both the intracellular and secreted IL-1ra was detected in
      unstimulated and IL-1beta- or phorbol 12-myristate 13-acetate-exposed RPE.
      Analysis of IL-1ra protein in RPE cell lysates and cell culture supernatants
      indicated that these cells produce mainly intracellular IL-1ra. No correlation
      between IL-1ra expression levels and the IL-1ra gene polymorphism could be
      detected. In addition to the two known intracellular IL-1ra variants
      (intracellular IL-1ra type I and type II) evidence is provided for the expression
      of a hitherto unknown splice variant of the IL-1ra mRNA by RPE cells. Expression
      was not confined to RPE cells and could also be detected in cultured human
      fibroblasts and macrophages. This variant, which we have tentatively named
      intracellular IL-1ra type III, encodes a C-terminally truncated protein of only
      27 amino acids.

PMID- 9933104
TI  - Direct and indirect T cell priming by dendritic cell vaccines.
AB  - The mechanisms by which dendritic cell (DC) vaccines prime host T cells in vivo
      was analyzed. Mice were immunized with syngeneic bone marrow-derived DC and as
      surrogate antigen beta-galactosidase (beta-gal) was used. DC either pulsed with
      peptide, loaded with beta-gal antigen or gene-modified induced beta-gal-specific
      cytotoxic T lymphocytes (CTL) and moderate rejection of an in vivo challenge with
      beta-gal expressing tumors. In addition, beta-gal-specific CTL lysed the
      syngeneic DC that were used as vaccines. Using SCID mice reconstituted with F1
      lymphocytes, direct priming by gene-modified DC vaccines was demonstrated by the
      presence of beta-gal-specific CTL of the haplotype exclusively expressed by DC
      while indirect priming by host antigen-presenting cells (APC) was shown by the
      detection of CTL of the haplotype exclusively present on host APC and absent on
      DC vaccines. Since DC immunization in syngeneic mice was associated with an
      increase in NK1.1+/Ly49C- cells and detectable lysis of DC in vitro by lymphokine
      activated killer cells, DC vaccines appear to interact with host natural killer
      cells as well as with antigen-specific T cells. These effector cells in turn may
      lyse DC vaccines thereby leading to the release of antigens that can be taken up
      by host APC.

PMID- 9933105
TI  - Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans.
AB  - It is now generally accepted that IFN-gamma, secreted by Th1 cells, is the most
      potent cytokine leading to macrophage activation and host resistance against
      infection with the intracellular protozoan parasite Leishmania. It is also
      established that IL-12 is a critical cytokine involved in the differentiation and
      expansion of Th1 cells. Therefore, the ability of Leishmania parasites to
      actively suppress IL-12 production by host macrophages may be an important
      strategy for parasite survival. Here we report that a major parasite cell surface
      molecule, phosphoglycan (PG), of Leishmania could selectively inhibit the
      synthesis of IL-12(p40, p70) by activated murine macrophages. Furthermore,
      synthetic PG (sPG) was able to inhibit IL-12 release in a dose-dependent manner.
      Inhibition was dependent on the galactose(beta1-4)mannose(alpha1)-PO4 repeating
      units and not the glycophosphoinositol lipid anchor of lipophosphoglycan. At the
      concentration used, sPG had no effect on the release of TNF-alpha or IL-6 in
      activated macrophages. The inhibition of IL-12(p40) production was at the
      transcriptional level, but was not mediated through NF kappaB inhibition. These
      data demonstrate that PG may be an important molecule for the establishment and
      survival of the parasite in permissive hosts.

PMID- 9933106
TI  - Cellular and molecular changes accompanying the progression from insulitis to
      diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is not a disease of unbridled
      destruction. The autoimmune attack on pancreatic beta cells has two distinct
      stages - insulitis and diabetes - and progression of the former to the latter
      appears to be highly regulated. Identifying the factors controlling this
      transition has been difficult because it is a complex process that occurs non
      universally and asynchronously. We have overcome these difficulties by coupling a
      simplified TCR transgenic (tg) model of IDDM and the immunosuppressive drug
      cyclophosphamide (CY). Young BDC2.5 TCR tg mice show insulitis but not diabetes;
      CY treatment provoked diabetes in 100% of animals with rapid, highly reproducible
      kinetics. This allowed a detailed temporal analysis of changes in cellular
      organization and cytokine gene expression within the lesion. The monokines IL-18,
      IL-12 and TNF-alpha were pivotal, their induction occurring almost immediately
      and their coordinate action being required for the onset of aggression. Other
      cytokines with direct toxicity for beta cells, including IL-1 -beta, IL-6 and IFN
      gamma, were subsequently induced; in contrast, there was no cellular or molecular
      evidence of cell contact-mediated mechanisms of beta cell death.

PMID- 9933107
TI  - IL-12 is a potent neonatal vaccine adjuvant.
AB  - Neonatal animals show generally poor responsiveness to foreign antigens and are
      known to display polarized expression of Th2-like cytokines and antibody
      responses. We now report that newborn mice display a reduction in peripheral
      expression of the Th1-inducing cytokine, IL-12. Attempts to overcome this
      decrease by immunization and treatment with IL-12 within 24 h of birth resulted
      in elevated levels of IFN-gamma and IL-10 mRNA in the spleens of mice compared to
      animals exposed to antigen only. Moreover, such animals showed dramatic
      enhancement of IgG2a and IgG2b antibody levels upon adult challenge compared to
      mice primed with antigen alone. These effects appeared to be due to induction of
      neonatal B cell memory. IgG1 antibody levels, a measure of Th2 activity, were
      unaffected or even somewhat enhanced by neonatal IL-12 treatment. Taken together,
      these results provide evidence that IL-12 administration induces a Th1-like
      cytokine response in newborns and causes priming for heightened memory antibody
      responses in vivo. Our findings suggest the use of IL-12 as a vaccine adjuvant in
      neonates for inducing protection against common childhood pathogens.

PMID- 9933108
TI  - Soluble CD14 acts as a negative regulator of human T cell activation and
      function.
AB  - T cell activation is controlled by the coordination of stimulatory and negative
      regulatory signals which are not completely defined. In this study we tested for
      a possible direct effect of CD14 on the regulation of T cell activation and
      function. We show that soluble CD14 (sCD14) induces inhibition of antigen
      mediated peripheral blood mononuclear cells (PBMC) proliferation and anti-CD3
      mediated proliferation of CD4+CD8+, CD4+CD8+ and CD4+CD8+ Tcell clones. This
      effect is not due to cell death, but results from a marked inhibition of IL-2
      production. Proliferation of T cell clones due to exogenous IL-2 is not affected
      by sCD14. We also found that sCD14 inhibits production of another Th1-like
      cytokine, IFN-gamma and a Th2-like cytokine, IL-4. Importantly, sCD14 induces a
      progressive accumulation of the inhibitory protein IkappaB-alpha. We show that
      sCD14 binds to activated T cells. Following cell activation, biotinylated sCD14
      stains CD3+ PBMC, as well as human T cell clones with varying intensity. The
      binding is saturable, can be inhibited by excess of unlabeled sCD14 and,
      following binding, sCD14 is internalized. Collectively, these findings reveal a
      previously unrecognized function of sCD14, namely its capacity to negatively
      regulate T lymphocyte activation and function by interacting directly with
      activated T cells.

PMID- 9933109
TI  - The ILT2(LIR1) and CD94/NKG2A NK cell receptors respectively recognize HLA-G1 and
      HLA-E molecules co-expressed on target cells.
AB  - Previous studies on NK recognition of HLA-G1 employed as targets 721.221
      transfectants (.221-G1) that unknowingly co-expressed the HLA-E molecule,
      subsequently found to be a major ligand for the CD94/NKG2 receptors. In the
      present study we re-evaluated the relative role played by CD94/NKG2 and
      ILT2(LIR1) molecules in recognition of HLA-G1 by NK clones. We employed as
      targets .221-G1 cells and a surface HLA-E-negative transfectant, .221-G1(Eneg),
      generated by site-directed mutagenesis of the HLA-G1 leader sequence. The
      antagonistic effects of receptor- (ie. CD94/NKG2A, ILT2) and ligand-specific mAb
      (i.e. HLA-G, HLA-E) were assessed. In addition, binding of an ILT2-Ig fusion
      protein to the .221-AEH, expressing only HLA-E, and the .221-G1(Eneg)
      transfectants was analyzed. Our data demonstrate that NK recognition of cells
      expressing HLA-G1 involves at least two non-overlapping receptor-ligand systems:
      the CD94/NKG2 interaction with HLA-E, and the engagement of the ILT2(LIR1)
      receptor by HLA-G1 molecules.

PMID- 9933110
TI  - Kinetics of the response of naive and memory CD8 T cells to antigen: similarities
      and differences.
AB  - We have studied the kinetics of the antigen induced response of naive and memory
      CD8 T cells expressing a transgenic T cell receptor (TCR) specific for the
      glycoprotein peptide amino acid 33-41 (GP33) of the lymphocytic choriomeningitis
      virus (LCMV). Memory T cells were generated in vivo by adoptive transfer of LCMV
      TCR transgenic T cells into normal recipient mice, followed by LCMV infection.
      The results demonstrated that the cell cycle progression and kinetics of TCR down
      modulation, CD25 and CD69 up-regulation were identical in naive and memory T
      cells after antigen recognition. Moreover, the two T cell populations did not
      differ in respect of activation thresholds and in their proliferative capacities
      neither in vitro nor in vivo. However, memory CD8 T cells could be more rapidly
      induced to become cytolytic and to secrete high levels of interleukin-2 and
      interferon-gamma than naive T cells. LCMV GP33-specific CD8 memory T cells were
      only slightly more efficient in reducing LCMV titers in the spleen but were far
      more effective than naive LCMV GP33-specific T cells in controlling subcutaneous
      tumor growth of B16.F10 melanoma cells which expressed the LCMV GP33 epitope as
      tumor-associated antigen. Thus, in our experiments the main difference between
      CD8 memory T cells and naive cells is the ability of the former to rapidly
      acquire effector cell functions.

PMID- 9933111
TI  - Distinct kinetics of cytokine production and cytolysis in effector and memory T
      cells after viral infection.
AB  - In the present study, naive T cells were compared with in vivo generated effector
      and memory T cells expressing the same TCR specific for lymphocytic
      choriomeningitis virus. Upon restimulation in vitro, the same minimal
      concentrations of the full agonist peptide p33 and also of weak and partial
      agonist peptides were required for proliferation of naive, effector and memory T
      cells, indicating no difference in threshold of activation. However, activation
      kinetics were distinct. While effector cytotoxic T cells exhibited immediate ex
      vivo lytic effector function, naive and memory T cells required 12 h and more
      exposure to antigen to develop lytic activity. However, both effector and memory
      T cells contained IFN-gamma mRNA in vivo and required less than 3 h for secretion
      of cytokines upon restimulation in vitro. In contrast, naive T cells did not
      contain IFN-gamma mRNA and required more than 12 h for cytokine secretion. Our
      results show that memory T cells exhibit a unique phenotype in that they produce
      cytokines and commit to proliferation as rapidly as effector cells, whereas they
      resemble naive T cells in the time requirement for development of cytolytic
      function.

PMID- 9933112
TI  - Activation of gp130 signaling in vivo by the IL-6 super-agonist K-7/D-6
      accelerates repopulation of lymphoid organs after irradiation.
AB  - Stimulation of the gp130 signaling pathway by IL-6 is known to contribute
      significantly to hematopoietic expansion in vitro, mostly in combination with
      other cytokines. In the present study we have investigated whether a similar
      effect can be observed also in vivo using short-term assays in which irradiated
      mice were analyzed for repopulation of lymphoid organs. Mice were injected with a
      combination of soluble IL-6Ralpha either with wild-type (wt) human IL-6 or with
      an IL-6 variant, called K-7/D-6, that shows a 70-fold higher IL-6Ralpha affinity.
      We observed that while wt IL-6 was able to induce a partial effect only in
      combination with IL-3, K-7/D-6 bypassed the need for IL-3 and yielded complete
      recovery. In lethally irradiated mice reconstituted with syngeneic bone marrow
      cells K-7/D-6 strongly accelerated the repopulation of thymus and spleen and
      hastened blood neutrophil recovery. These results underscore the potential of the
      gp130 signaling pathway in hematopoietic reconstitution after myeloablative
      regimens and open the possibility to fully exploit it with a super-active IL-6
      variant.

PMID- 9933113
TI  - CTLA4-Ig inhibits optimal T helper 2 cell development but not protective immunity
      or memory response to Nippostrongylus brasiliensis.
AB  - The B7 co-stimulatory pathway is critical to T cell activation, however its role
      in the generation of Th2 cells in vivo remains controversial. We have studied the
      role of B7 co-stimulation in the development of a Th2 immune response to the
      nematode parasite Nippostrongylus brasiliensis. Blockade of B7 co-stimulation
      with murine CTLA4-Ig (mCTLA4-Ig) resulted in decreased Th2 cell development as
      determined by IL-4 and IL-5 cytokine production in vitro. It also resulted in
      lowered Th2 cell effector function in vivo, with marked reductions in IgE
      production. Blood eosinophilia was variably affected by mCTLA4-Ig treatment,
      which resulted in both slight and very severe inhibition in different
      experiments. However, an effective immune response was still evident as
      demonstrated by the further reduction of cytokine production, IgE titers, and
      blood eosinophilia in mice treated with a combination of mCTLA4-Ig and anti-CD4
      mAb, and by the ability of mCTLA4-Ig-treated mice to expel adult worms. In
      addition, mCTLA4-Ig treatment did not alter the development of a memory response
      following secondary infection with N. brasiliensis, with the exception of IgE
      production. We conclude from these results that B7 co-stimulation is required in
      this experimental model for optimal Th2 cell development and effector function in
      vivo but is not necessary for protective immunity.

PMID- 9933114
TI  - Recombinant IFN-gamma abrogates allograft tolerance induced by donor-specific
      blood transfusion by restoring alloantibody production.
AB  - Donor-specific tolerance to heart allograft was induced in adult Lewis rats by
      pregraft donor-specific blood transfusion (DST). We previously showed that this
      tolerant state is characterized by a dramatic inhibition of T cell and macrophage
      activation. In addition, tolerant animals could not mount an efficient anti-donor
      humoral response whereas transfer of sera from rejecting animals triggered
      rejection in tolerant animals. This tolerance can be abrogated by daily post
      graft administration of recombinant IFN-gamma (rIFN-gamma). To elucidate the
      mechanisms of action of rIFN-gamma, T cell, macrophage and B cell functions were
      assessed in allograft recipients. IFN-gamma did not restore the expression of Th1
      related cytokine mRNA or the activated macrophage product inducible nitric oxide
      synthase in allografts. Importantly, rIFN-gamma treatment promptly restored the
      anti-donor humoral response in DST-treated recipients. We conclude that rIFN
      gamma treatment in DST-treated allograft recipients cannot reverse the
      unresponsive state of Th1 cells and macrophages infiltrating the graft, but can
      provide B cell help for IgG alloantibody production which is lacking in these
      animals.

PMID- 9933115
TI  - B and also T lymphocytes migrate via gut lymph to all lymphoid organs and the gut
      wall, but only IgA+ cells accumulate in the lamina propria of the intestinal
      mucosa.
AB  - In pigs the lymphocytes emigrating from the intestinal wall were collected by
      cannulating the lymphatics, labeled in vitro using a fluorescent dye and
      retransfused. The injection of 6.6+/-4.2 x 10(8) cells resulted in a labeling
      index between 1.5% in intestinal lymph, 0.2% in the spleen and lymph nodes,
      approximately 0.1% in the intestinal lamina propria and 0.003% in intraepithelial
      lymphocytes. About 25 % of the injected cells were present in the blood and 1 %
      was recovered in the lymph. T cells were found in similar proportions in the
      injected and the recovered cells in the organs (70-80%). The proportion of IgA+
      cells among the immigrated cells in the intestinal lamina propria ranged from 5
      to 8%, which in absolute numbers was up to 60% of the injected IgA+ cells. T and
      IgM+ cells did not show a higher accumulation in any organ. These experiments in
      conventional, unrestrained animals revealed that (1) T cells immigrate into the
      intestinal lamina propria, (2) preferential migration of IgA+ cells from gut
      lymph to the intestinal lamina propria is obvious under in vivo conditions and
      (3) the immigrated IgA+ cells represent a very small population which is
      difficult to detect when analyzed in relative numbers.

PMID- 9933116
TI  - Growth hormone prevents human monocytic cells from Fas-mediated apoptosis by up
      regulating Bcl-2 expression.
AB  - Apoptosis and particularly Fas-mediated apoptosis has been proposed to play a key
      role in controlling monocyte homeostasis. We and others have documented the
      regulatory function of human growth hormone (hGH) on monocytic cells, which
      prompted us to investigate the role of hGH on their response to Fas antigen cross
      linking. Using human promonocytic U937 cells constitutively producing hGH upon
      gene transfer and human primary monocytes cultured in the presence of recombinant
      hGH, we demonstrated that hGH diminished Fas-mediated cell death by enhancing the
      expression of the antiapoptotic oncoprotein Bcl-2 as well as the level of bcl
      2alpha mRNA. In parallel, we established that overexpression of Bcl-2 through
      gene transfer into normal U937 cells also diminished Fas-induced apoptosis.
      Further, as a result of Bcl-2 overexpression, we found that hGH greatly depressed
      Fas-induced activation of the cysteine protease caspase-3 (CPP32), which in turn
      affected the cleavage of poly(ADP-ribose) polymerase. Altogether, these data
      provide evidence that hGH mediates its protective effect through a Bcl-2
      dependent pathway, clearly a crucial step in enhanced survival of monocytic cells
      exposed to Fas-induced death.

PMID- 9933117
TI  - Chronic intravenous injections of antigen induce and maintain tolerance in T cell
      receptor-transgenic mice.
AB  - Antigen-specific T cell tolerance can be induced by systemic injection of high
      dose antigen. In particular, a single intravenous (i.v.) injection of influenza
      virus hemagglutinin peptide in HNT-TCR transgenic mice induces T cell tolerance
      through thymocyte apoptosis as well as anergy and deletion of peripheral CD4+ T
      cells. We now show that this tolerance is reversed after 8 weeks probably due to
      the short in vivo half-life of the peptide. Since durable tolerance is required
      for this strategy to be of therapeutic value, we tested whether weekly i.v.
      injections of peptide (up to 12 weeks) could maintain the CD4+ T cell tolerance.
      Each injection induces a profound deletion of thymocytes, although their level
      recovers before the next injection. Therefore, during the treatment period, the
      thymus undergoes cycles of contraction/expansion. In the periphery, the number of
      CD4+ T cells is stably decreased and the persisting CD4+ T cells are hyporeactive
      both in vitro and in vivo. This tolerance is essentially peripheral since
      comparable results were obtained in thymectomized HNT-TCR mice injected weekly.
      Our data show that stable antigen-specific tolerance can be induced by repeated
      i.v. injections of antigen. These findings might have implications for the
      treatment of T cell-mediated autoimmune diseases.

PMID- 9933118
TI  - A synthetic mimetic of CD4 is able to suppress disease in a rodent model of
      immune colitis.
AB  - CD4+ mucosal T cells mediate the intestinal inflammation in Crohn's disease and
      may serve as an important target for immune intervention. Here we assessed the
      therapeutic effect of a synthetic mimetic of CD4 designed to mimic both the
      sequence and conformation of the complementarity-determining region 3 of murine
      CD4 V1 domain (rD-mPGPtide) in a mouse colitis model using immunization with
      2,4,6-trinitrobenzene sulfonic acid (TNB). i.v. administration of the rD-mPGPtide
      but not control scrambled peptide could suppress severe inflammation in the
      chronic colitis mouse model. After treatment with the rD-mPGPtide, a striking
      improvement of diarrhea and acute wasting disease was observed with decreased
      mortality. Serum anti-TNB antibody titers, CD45RBlowCD4+ T cells in the lamina
      propria and IFN-gamma mRNA expression in the mucosa were significantly decreased
      with the rD-mPGPtide treatment. Anti-CD4 antibody also suppressed disease by
      depletion of CD45RBhighCD4+ T cells in the colonic mucosa. The observation that
      the synthetically engineered analogue of murine CD4 inhibits inflammation in a
      rodent disease model by different mechanisms than anti-CD4 antibody suggests that
      a human version of this peptide has potential therapeutic utility in CD4+ mucosal
      T cell-mediated intestinal inflammation in Crohn's disease.

PMID- 9933120
TI  - All-terrain vehicle-related deaths--West Virginia, 1985-1997.
AB  - From 1985 through 1997, the U.S. Consumer Product Safety Commission (CPSC)
      identified 113 deaths associated with all-terrain vehicles (ATVs) in West
      Virginia. This report summarizes data from the CPSC ATV-related death database
      and on-site and/or follow-up telephone investigations; findings indicate that
      approximately two thirds of deaths were caused by injury to the head or neck.
      Consistent use of helmets by riders can substantially reduce ATV-related deaths.

PMID- 9933119
TI  - CD40 ligand expression deficiency in a female carrier of the X-linked hyper-IgM
      syndrome as a result of X chromosome lyonization.
AB  - We report on the case of a girl with an immune deficiency characterized by
      recurrent infections of the upper and lower respiratory tract, low IgG and IgA
      serum levels as well as deficiency of the in vivo antibody response. Since this
      patient is the sister of a boy affected with a hyper-IgM syndrome due to a defect
      in CD40 ligand (CD40L) expression, the involvement of CD40L in this phenotypic
      expression was investigated. A very low fraction of activated T cells (5%) in
      this female patient expressed CD40L. This resulted from the presence of a
      heterozygous CD40L nonsense mutation associated with a skewed pattern of X
      chromosome inactivation as determined by methylation pattern analysis. Although
      carriers of X-linked hyper-IgM are considered to be asymptomatic, this study
      indicates that extreme lyonization of the normal X can lead to a mild expression
      of the hyper-IgM syndrome which is similar to common variable immune deficiency
      (CVID). Therefore, it is possible that some cases of CVID in females represent
      partial deficiency of CD40L expression in carriers of the CD40L mutation.

PMID- 9933121
TI  - False-positive laboratory tests for Cryptosporidium involving an enzyme-linked
      immunosorbent assay--United States, November 1997-March 1998.
AB  - From November 1997 through March 1998, the number of positive tests for
      Cryptosporidium increased in several locations in the United States. Several
      laboratories (e.g., the New York state laboratory and the Medical Science
      Laboratories in Wisconsin) retested original stool specimens and could not
      confirm the original positive test result. Following reports to the manufacturer
      by the Massachusetts, New York, and Wisconsin state health departments about
      possibly inaccurate test results, Alexon-Trend (Ramsey, Minnesota) notified its
      laboratory customers in a March 25, 1998, letter that three lots of its enzyme
      linked immunosorbent assay (ELISA) 24 well (catalog number 540-24) ProSpecT
      Cryptosporidium Microplate Assay (lot numbers 970717,975011, and 980401) and
      seven lots of its ELISA 96 well (catalog number 540-96) ProSpect Cryptosporidium
      Microplate Assay (lot numbers 970696, 970775, 970883, 975006, 980402, 980808, and
      980809) were subject to a "non-specific reaction between some stool specimens and
      the microplate assay" (i.e., a false-positive test result) (K. Hood, Alexon
      Trend, personal communication, March 25, 1998). Alexon-Trend directed
      laboratories to discontinue using kits with implicated lot numbers. This report
      summarizes an analysis of reports of false-positive tests and describes
      identification of apparent clusters in three states.

PMID- 9933122
TI  - Self-reported prevalence of diabetes among Hispanics--United States, 1994-1997.
AB  - Diabetes disproportionately affects the Hispanic population in the United States.
      Most diabetes studies that focused on Hispanics have been conducted among Mexican
      Americans and have found that approximately one out of every 10 persons aged > or
      =20 years has diabetes. However, the U.S. Hispanic population comprises many
      ethnically distinct groups that tend to be regionally concentrated. CDC analyzed
      data from the Behavioral Risk Factor Surveillance System (BRFSS) to assess the
      prevalence of diabetes among Hispanic adults in the United States and Puerto
      Rico. This report presents the findings of this analysis, which indicate that the
      prevalence of diabetes among U.S. Hispanics is approximately twice the prevalence
      among non-Hispanic whites and varies by geographic location and education.

PMID- 9933123
TI  - Recommended childhood immunization schedule--United States, 1999.
AB  - Each year, CDC's Advisory Committee on Immunization Practices (ACIP) reviews the
      recommended childhood immunization schedule to ensure it remains current with
      changes in manufacturers' vaccine formulations, revised recommendations for the
      use of licensed vaccines, and recommendations for newly licensed vaccines. This
      report presents the recommended childhood immunization schedule for 1999 and
      explains the changes that have occurred since January 1998.

PMID- 9933124
TI  - Update: influenza activity--United States, 1998-99 season.
AB  - In collaboration with the World Health Organization (WHO), its collaborating
      laboratories, and state and local health departments, CDC conducts surveillance
      to monitor influenza activity and to detect antigenic changes in the circulating
      strains of influenza viruses. This report summarizes influenza surveillance in
      the United States from October 4, 1998, to January 9, 1999, which indicates that
      overall influenza activity was low.

PMID- 9933125
TI  - Adult lead poisoning from an Asian remedy for menstrual cramps--Connecticut,
      1997.
AB  - Follow-back procedures to determine the source of elevated blood lead levels
      (BLLs) are integral parts of the CDC's National Institute for Occupational Safety
      and Health Adult Blood Lead Epidemiology and Surveillance program (ABLES) in 27
      states. Although an estimated 90%-95% of cases of elevated BLLs reported to the
      states in the ABLES program result from occupational exposures, nonoccupational
      exposures also are identified by this system. This report describes a case of
      adult lead poisoning attributed to an Asian remedy for menstrual cramps, "Koo
      Sar" pills, following an investigation by the Adult Lead Registry of the
      Connecticut Department of Public Health (CDPH), Division of Environmental
      Epidemiology and Occupational Health.

PMID- 9933126
TI  - Final stages of poliomyelitis eradication--Western Pacific Region, 1997-1998.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by 2000. A plan of action for polio eradication in the Western Pacific Region
      (WPR) by 1995 was adopted in 1990. The plan was based on routine and supplemental
      vaccination activities with oral poliovirus vaccine (OPV) and acute flaccid
      paralysis (AFP) surveillance in the eight countries where polio was endemic
      (Cambodia, China, Laos, Malaysia, Mongolia, Papua New Guinea, Philippines, and
      Vietnam). Regionwide, the number of reported polio cases decreased from
      approximately 6000 in 1990 to zero in 1998. This report describes the extensive
      efforts to eliminate the last chains of poliovirus transmission in the Mekong
      River area.

PMID- 9933127
TI  - Update: recommendations to prevent hepatitis B virus transmission--United States.
AB  - In October 1997, the Advisory Committee on Immunization Practices (ACIP) expanded
      its hepatitis B vaccination recommendations to include all unvaccinated children
      aged 0-18 years and made hepatitis B vaccine available through the Vaccines for
      Children program (VFC) for persons aged 0-18 years who are eligible for VFC. ACIP
      priorities for hepatitis B vaccination of children remain unchanged and include
      all infants; children in populations at high risk for hepatitis B virus (HBV)
      infection (e.g., Alaska Natives, Pacific Islanders, and children who reside in
      households of first-generation immigrants from countries where HBV infection is
      moderately or highly endemic); previously unvaccinated children aged 11-12 years;
      and older adolescents and adults in defined risk groups.

PMID- 9933128
TI  - Availability of Lyme disease vaccine.
AB  - On December 21, 1998, the Food and Drug Administration (FDA) licensed LYMErix
      (SmithKline Beecham Biologicals, Reixensart, Belgium), a new vaccine against Lyme
      disease (LD). This report summarizes information about this vaccine and provides
      epidemiologic information about LD relevant to vaccine use.

PMID- 9933130
TI  - Neuroleukin mediated differentiation induction of myelogenous leukemia cells.
AB  - Leukemia cells enriched from peripheral blood of a patient with myelogenous
      leukemia were induced to differentiate with a purified T cell lymphokine
      neuroleukin. With sufficient neuroleukin concentrations, cells with macrophage
      like morphology were identified among the developing adherent cells. After 2-5
      days, approximately 38-50% of the suspension cells became macrophage-like and
      acquired CD21, alpha-naphthyl acetate reactivity and immune adherence capability.
      The amount of these nonproliferating cells increased along with cells containing
      fragmented DNA. Induction with insufficient neuroleukin quantity or with patient
      plasma alone developed few or no mature cells, indicating differentiation to
      mature cells is dose-dependent. The possibility of insufficient quantity of
      neuroleukin in regulation of patient plasma for differentiation was discussed.

PMID- 9933129
TI  - Role of physiologic concentrations of stem cell factor in leukemic type growth of
      myelodysplastic CD34+ cells.
AB  - The stem cell factor (SCF: a ligand for c-kit) plays a central role in the growth
      of myelodysplastic (MDS) progenitor cells with leukemic type growth. In this
      study, the role of physiologic concentrations of SCF on the proliferation and
      differentiation on MDS progenitor cells was further analyzed in the presence of
      combined cytokines. For this purpose, marrow CD34+ cells were purified up to 94%
      for 12 normal individuals and 90% for 18 MDS patients, using monoclonal
      antibodies and immunomagnetic microspheres. The purified CD34+ cells were
      cultured for 14 days with saturating doses of cytokines, including recombinant
      human macrophage colony stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF),
      granulocyte/macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3) and rSCF. The clonal
      growth of MDS CD34+ cells supported by a combination of all the above cytokines
      was then subdivided into the two patterns of leukemic or non-leukemic. The role
      of various concentrations of rSCF (0, 0.5, 5, 50 and 500 ng ml(-1)), with or
      without the above cytokines, in proliferation and differentiation of MDS CD34+
      cells was analyzed in each group. The physiologic concentration of SCF at 5 ng
      ml(-1) significantly increased undifferentiated 'blast cell' colonies or clusters
      in leukemic type growth of MDS CD34+ cells over that seen in normal CD34+ cells.
      SCF is present in plasma at a level of ng ml(-1). This means that progenitor
      cells are continuously exposed to stimulation by SCF in vivo and that MDS
      leukemic cells have a growth advantage over normal blasts.

PMID- 9933131
TI  - Heterogeneity of T-acute lymphoblastic leukemia (T-ALL) cell lines: suggestion
      for classification by immunophenotype and T-cell receptor studies.
AB  - Hematopoietic cell lines are often used as representatives for a certain cell
      differentiation lineage and stage, particularly in immunological and
      hematological studies. Acute lymphoblastic leukemia (ALL) of T-cell type is a
      rather heterogeneous group of ALL at least by immunophenotyping. Our aim was to
      present a comprehensive characterization of frequently used T-cell leukemia cell
      lines and to suggest a correlation with the normal differentiation pattern. A
      total of 16 T-ALL cell lines were analyzed for their immunophenotype and for T
      cell receptor (TCR) rearrangement and expression. The panel of 20 cell surface
      markers included two new monoclonal antibodies (MoAb), TC-12 and TH-111, which
      were raised in our laboratory and detect subpopulations of T-cell ALL. TC-12 was
      typed 'unique', TH-111 was assigned to the CD96 cluster at the Vth Conference on
      human leucocyte differentiation antigens (HLDA). We categorized the 16 cell lines
      into the four groups pro-T, pre-T, cortical T and mature T differentiation stage
      according to the recent proposal of the European Group for the Immunological
      Characterization of Leukemias (EGIL). Interestingly, none of the T-cell lines
      were found to be alike. In conclusion, it appears necessary to consider the
      particular differentiation stage of each individual cell line when using T-cell
      leukemia lines as models for malignant or normal T cells.

PMID- 9933132
TI  - Effect on cell kill of addition of multidrug resistance modifiers cyclosporin A
      and PSC 833 to cytotoxic agents in chronic lymphocytic leukaemia.
AB  - Expression of P-glycoprotein (Pgp), the drug efflux pump which mediates multidrug
      resistance (MDR), has been widely reported in chronic lymphocytic leukaemia (CLL)
      and improved accumulation of daunorubicin has been reported using the MDR
      reversing agent cyclosporin A (CSA). We have investigated the effects on cell
      kill of the addition of CSA and its analogue PSC 833 to daunorubicin,
      doxorubicin, idarubicin, mitozantrone and fludarabine in samples from 51 patients
      with CLL using an MTT [3(4,5-dimethylthaizol-2-yl)-2,5-diphenyltetrazolium
      bromide] assay. Pgp expression was assessed by immunocytochemistry using the JSB
      1 monoclonal antibody. Of the 51 samples, 10 (20%) were Pgp positive and all of
      these samples were from treated patients. With the exception of mitozantrone, the
      addition of CSA and PSC 833 to cytotoxic agents failed to significantly improve
      cytotoxicity, even in the Pgp positive group. With mitozantrone significant
      responses were seen in both Pgp positive and negative groups suggesting that the
      responses were due to direct cytotoxicity of the cytotoxic-modifier combination
      rather than reversal of MDR. Both CSA and PSC 833 showed significant direct
      cytotoxicity (P = 0.004 and 0.04 for PSC 833 at 1000 ng/ml and 500 ng/ml
      respectively; P < 0.001 for both concentrations of CSA). The responses were
      disappointing compared to the highly significant improvements in cytotoxicity
      seen using cells from the Pgp positive CEM VLB 100 acute myeloid leukaemia cell
      line, and it was not possible to demonstrate the superiority of PSC 833 over CSA
      which is also seen in cell lines. Our data do not support a role for Pgp
      modifiers in CLL. Further studies using larger numbers of Pgp positive CLL cells
      and higher doses of PSC 833 would be useful.

PMID- 9933133
TI  - Effect of PSC 833 on the cytotoxicity of idarubicin and idarubicinol in multidrug
      resistant K562 cells.
AB  - We examined the effect of PSC 833, a non-immunosuppressive cyclosporin analogue,
      on the cytotoxicity, accumulation and retention of idarubicin (IDA) and its 13
      dihydro metabolite, idarubicinol (IDAol). P-glycoprotein (PGP)-overexpressing
      multidrug-resistant K562/D1-9 cells were used for these studies. PSC 833 had no
      effect on the cytotoxicity, intracellular accumulation, or retention of IDA and
      IDAol in the parent K562 cells. However, intracellular accumulation of IDA and
      IDAol in K562/D1-9 cells after a 60-min incubation was restored by 0.4 microM PSC
      833 to 104% and 116%, respectively, of the level in parent K562 cells. The
      retention of IDA and IDAol in K562/D1-9 cells was also restored by 0.4 microM PSC
      833. Consequently, 0.4 microM PSC 833 increased the sensitivity of K562/D1-9
      cells to IDA and IDAol. The resistance index (RI) of IDA decreased from 20-fold
      to 4.0-fold, and the RI of IDAol decreased from 104-fold to 1.5-fold. These
      results suggest that the combination of IDA and PSC 833 may be effective in
      reversing PGP-mediated multidrug resistance in leukemia cells.

PMID- 9933134
TI  - Boswellic acid acetate induces differentiation and apoptosis in leukemia cell
      lines.
AB  - Boswellic acid acetate (BC-4), a compound isolated from the herb Boswellia
      carterii Birdw., can induce differentiation and apoptosis of leukemia cells.
      Based on cell morphology and NBT reduction, BC-4 induced monocytic
      differentiation of myeloid leukemia HL-60, U937 and ML-1 cells at a dose under
      12.5 microg/ml (24.2 microM). BC-4 was a potent inducer, with 90% of the cells
      showing morphologic changes and 80-90% of the cells showing NBT reduction.
      Specific and non-specific esterase were also increased by BC-4. Based on
      benzidine staining assay, BC-4 failed to induce erythroid leukemia DS-19 and K562
      cells differentiation. In contrast to its selective differentiation effect, BC-4
      strongly inhibited growth of all cell lines tested. The growth inhibition effect
      was dose- and time-dependent. In HL-60 cells, 20 microg/ml (38.8 microM) of BC-4
      decreased viable cell number by 60% at 24 h, whereas at 3 days there was
      virtually no viable cells. Morphologic and DNA fragmentation analysis proved that
      BC-4 induced cell apoptosis. The dual apoptotic and differentiation effects of BC
      4 suggest that it may be a powerful agent in the treatment of leukemia.

PMID- 9933135
TI  - Do lipoxygenases modulate normal or aberrant lympho-hematopoiesis?
AB  - Whether 5- (and the 12- or 15-) lipoxygenases participate in normal or
      malignantly transformed hematopoietic cell proliferation and differentiation, or
      contribute to programmed or necrotic cell death has been difficult to decide.
      Recent evidence concerning these questions is reviewed and some reasons for these
      difficulties are considered.

PMID- 9933136
TI  - Hair dye use and occupational exposure to organic solvents as risk factors for
      myelodysplastic syndrome.
AB  - To investigate the relationships of personal hair dye use and environmental
      factors to myelodysplastic syndromes (MDS), we conducted a case-control study in
      Japan. A total of 111 MDS cases and 830 controls randomly selected from the
      residents in the same prefecture of cases using telephone directories responded
      to a health questionnaire. The odds ratio (OR) for ever having used hair dye was
      1.99 (95% confidence interval (CI) 1.17-3.38) and there were statistically
      significant trends in risk with increasing duration and number of hair dye use.
      Occupational exposure to organic solvents was marginally associated with the risk
      of MDS (OR = 1.99; 95% CI 0.97-4.10).

PMID- 9933137
TI  - Correlation between lower c-mpl protein expression and favorable cytogenetic
      groups in acute myeloid leukemia.
AB  - The gene for the thrombopoietin receptor, c-mpl, has been shown to be
      overexpressed at the mRNA level in acute myeloid leukemia (AML) and
      myelodysplastic syndrome. A recent study reported c-mpl mRNA overexpression in
      60% of a small sample of AML patients, and this overexpression correlates with
      shorter complete remission but not with karyotype group. We quantified c-mpl
      protein expression in 107 cases of AML and 24 normal bone marrow and 12 normal
      peripheral blood samples by using Western blot analysis and radioimmunoassay
      (RIA). Western blot analysis revealed no detectable level of c-mpl protein in the
      normal samples, whereas trace amounts were detected by RIA. c-mpl protein
      expression was increased (> or = twice normal) in 65% of the AML cases. c-mpl
      protein expression was correlated with cytogenetic groups (P = 0.0009, Kruskal
      Wallis test in rejecting the hypothesis that c-mpl expression was the same in
      different groups). Specifically, patients with favorable cytogenetic groups
      (t(8;21), inv16, and t(15;17)) had lower c-mpl protein expression (median 1.7
      times normal), whereas patients with unfavorable abnormalities (+8, -5 or -7, and
      del(11)(q23)) and normal cytogenetics had high expression (3.1 and 2.85 times
      normal, respectively). The findings were the same when only the 61 untreated AML
      patients were considered. No statistically significant correlation between c-mpl
      expression and age or antecedent hematologic disorder was found. These results
      suggest that c-mpl protein overexpression in AML may play a role in the
      aggressiveness of this disease.

PMID- 9933138
TI  - Open heart surgery in patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: Chronic leukemia is a disease characterized by the malignant
      proliferation of immunologically incompetent lymphocytes. The knowledge of open
      heart surgery in patients with this disorder is limited. METHODS: Twelve patients
      with chronic lymphocytic leukemia underwent open heart surgery (nine coronary
      artery bypass grafting (CABG), two aortic valve replacement (AVR), one CABG and
      AVR) from September 1991 to September 1996. There were nine males and three
      females with a mean age of 68 years (41-81 years). Staging was assigned according
      to the Rai Classification. There were seven Stage 0, two Stage I, zero Stage II,
      one Stage III and two Stage IV patients. Cardiopulmonary bypass (CPB) was
      performed using standard techniques of cannulation, moderate hypothermia and
      antegrade/retrograde cardioplegia. RESULTS: Hospital mortality occurred in two
      (17%) patients. Both patients died of sepsis. Hospital morbidity occurred in
      seven (58%) patients. The most common complications were infections. Five
      patients were found to have other malignancies (basal cell, laryngeal, prostate,
      bladder and breast cancers). Transfusion of blood products was required in eight
      (67%) patients. The average length of stay was 15 days (7-50 days). Follow-up was
      complete. Late mortality occurred in four patients at a mean of 7 months (1-18
      months). All deaths were non-cardiac related (ruptured AAA, kidney failure,
      respiratory failure and sepsis). Six patients remain alive at a mean of 25 months
      (1-48 months). CONCLUSION: Hospital mortality and morbidity in patients with
      chronic lymphocytic leukemia undergoing open heart surgery are high. Infection is
      the leading cause of hospital death, as well as the most common complication. The
      majority of patients receive blood products during the course of their
      hospitalization. Late mortality is high and non-cardiac related. Based on these
      findings, a re-definition of the aims, goals and expectations of open heart
      surgery in patients with chronic leukemia is necessary. Suggestions in management
      are presented.

PMID- 9933139
TI  - Limited erythropoietic response to combined treatment with recombinant human
      interleukin 3 and erythropoietin in myelodysplastic syndrome.
AB  - Twenty-two patients with myelodysplastic syndrome were treated with combined
      recombinant human erythropoietin and recombinant human interleukin 3 (rHuIL-3).
      All 22 patients were evaluable for toxicity and 21/22 for response. Thirteen
      patients (62%) required rHuIL-3 dose reduction because of toxicity. Nineteen
      experienced a 50% or greater rise in neutrophil count. Of seven patients with
      initial platelet counts of > 100,000, three experienced increases of > 15,000/ml
      while an equal number had a comparable decline. Five patients (21%) experienced a
      significant rise in reticulocyte count, and two transfusion-dependent patients
      experienced a significant decrease in transfusions. Erythroid burst-forming units
      were increased by > or = 50% in nine of 11 patients after combined therapy.
      Similar changes were seen in multipotential colony-forming units. Clinical
      responses were comparable to results obtained with epo alone while toxicities due
      to IL-3 were significant.

PMID- 9933140
TI  - Acute myeloid leukemia with hypergranular cytoplasm accompanied by
      t(X;11)(q24;q23) and rearrangement of the MLL gene.
AB  - This report describes a unique case of acute myeloid leukemia with hypergranular
      cytoplasm and t(X;11)(q24;q23). The breakpoint on 11q23 was identified within the
      MLL gene. The hypergranular cytoplasm of leukemic cells and the associated
      coagulopathy resembled a characteristic of acute promyelocytic leukemia, despite
      the absence of RARalpha gene rearrangement in this case. The Xq24 site possibly
      played a role in this atypical blast phenotype.

PMID- 9933141
TI  - The short form of PML-RARalpha fusion transcript is associated with poor
      survival.

PMID- 9933142
TI  - Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned
      human 5-HT2A, -HT(2B) and 5-HT2C receptors.
AB  - Since the classical hallucinogens were initially reported to produce their
      behavioral effects via a 5-HT2 agonist mechanism (i.e., the 5-HT2 hypothesis of
      hallucinogen action), 5-HT2 receptors have been demonstrated to represent a
      family of receptors that consists of three distinct subpopulations: 5-HT2A, 5
      HT2B, and 5-HT2C receptors. Today, there is greater support for 5-HT2A than for 5
      HT2C receptor involvement in the behavioral effects evoked by these agents.
      However, with the recent discovery of 5-HT2B receptors, a new question arises: do
      classical hallucinogens bind at 5-HT2B receptors? In the present study we
      examined and compared the binding of 17 phenylisopropylamines at human 5-HT2A, 5
      HT2B, and 5-HT2C receptors. Although there was a notable positive correlation
      (r>0.9) between the affinities of the agents at all three populations of 5-HT2
      receptors, structural modification resulted only in small differences in 5-HT2B
      receptor affinity such that the range of affinities was only about 50-fold. As
      with 5-HT2A and 5-HT2C receptor affinity, there is a significant correlation
      (r>0.9, n=8) between 5-HT2B receptor affinity and human hallucinogenic potency.
      Nevertheless, given that 5-HT2A and 5-HT2A/2C antagonists - antagonists with low
      affinity for 5-HT2B receptors - have been previously shown to block the stimulus
      effects of phenylisopropylamine hallucinogens, it is likely that 5-HT2A receptors
      play a more prominent role than 5-HT2B and 5-HT2C receptors in mediating such
      effects despite the affinity of these agents for all three 5-HT2 receptor
      subpopulations.

PMID- 9933143
TI  - Comparison of CGS 15943, ZM 241385 and SCH 58261 as antagonists at human
      adenosine receptors.
AB  - Three structurally related non-xanthine compounds, CGS 15943, ZM 241385 and SCH
      58261, are potent A2A adenosine receptor antagonists and have been used as tools
      in many pharmacological studies. We have now characterized their affinity and
      selectivity profile on human adenosine receptors stably transfected into either
      CHO cells (A1 and A2B receptors) or HEK-293 cells (A2A and A3 receptors). In
      binding studies using [3H]SCH 58261 as a radioligand, the three compounds were
      equally potent at A2A receptors, their K(i) value being less than 1 nM. Affinity
      for A1 and A3 receptors was measured using [3H]DPCPX and [125I]AB-MECA as
      radioligands. Given the lack of selective ligands, interaction with A2B receptors
      was assessed using the cAMP accumulation assay following stimulation by the
      adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA). CGS 15943 was
      almost as potent at A1 receptors (K(i)3.5 nM) as at A2A receptors, showed
      moderate affinity for A3 receptors (K(i) 95 nM) and also interacted with A2B
      receptors (K(i) 44 nM; pA2 7.5). ZM 241385 showed little affinity for A1
      receptors (K(i) 255 nM), and did not interact with A3 receptors (K(i)>10 microM);
      however, it displayed moderate affinity for A2B receptors (K(i) 50 nM; pA2 7.3).
      SCH 58261 had weak affinity for A1 receptors (K(i) 287 nM), no interaction with
      A3 receptors (K(i)>10 microM), and showed negligible interaction with A2B
      receptors (K(i) 5 microM; pA2 6.0). These data indicate that SCH 58261 is the
      most selective A2A antagonist currently available. Moreover, the different
      receptor selectivity of these three chemically related compounds provides useful
      information to progress with structure-activity relationship studies.

PMID- 9933144
TI  - Histaprodifen, methylhistaprodifen, and dimethylhistaprodifen are potent H1
      receptor agonists in the pithed and in the anaesthetized rat.
AB  - Selective H2- and H3-receptor agonists, exhibiting an at least tenfold higher
      potency than histamine itself at the respective receptors, have been known for
      several years. Selective H1-receptor agonists with a potency exceeding that of
      histamine have become available only recently; the most potent are
      methylhistaprodifen and dimethylhistaprodifen [Nalpha-methyl- and Nalpha,Nalpha
      dimethyl-2(3,3-diphenylpropyl)histamine, respectively] with 3.4- and 2.4-fold
      higher potencies than histamine in vitro (in the guinea-pig ileum). The aim of
      the present study was to examine whether these compounds and the parent compound
      histaprodifen are potent H1-receptor agonists in the pithed and in the
      anaesthetized rat. In pithed, vagotomized rats diastolic blood pressure was
      decreased by 2-(2-thiazolyl)ethanamine i.v. (which was used as a reference H1
      receptor agonist) and by histaprodifen, methylhistaprodifen, and
      dimethylhistaprodifen; the maximum decrease was about 45 mmHg for each compound,
      and the potencies, expressed as pED50, the negative logarithm of the dose (in
      mole per kilogram body weight) eliciting a half-maximal response, were 7.23,
      7.55, 8.43 and 8.12, respectively. The dose/response curves of the four compounds
      were shifted to the right to about the same extent by the H1-receptor antagonist
      dimetindene (1 micromol/kg i.v.). The vasodepressor response was not affected by
      combined i.v. administration of the H2- and H3-receptor antagonists ranitidine
      and thioperamide, by combined i.v. administration of the alpha1- and alpha2
      adrenoceptor antagonists prazosin and rauwolscine, and by the beta-adrenoceptor
      antagonist propranolol i.v. but was attenuated by the inhibitor of NO synthase,
      N(omega)-nitro-L-arginine methyl ester i.v. In anaesthetized rats 2-(2
      thiazolyl)ethanamine, histaprodifen, methylhistaprodifen and
      dimethylhistaprodifen i.v. also decreased diastolic blood pressure in a manner
      sensitive to dimetindene i.v. Our data show that histaprodifen and, in
      particular, methyl and dimethylhistaprodifen are highly potent H1-receptor
      agonists in vivo.

PMID- 9933145
TI  - The stereoselective kappa-opioid receptor antagonist Mr 2266 does not exhibit
      stereoselectivity as an antagonist at the orphan opioid (ORL1) receptor.
AB  - Mr 2266 [(-)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorpha
      n] is an antagonist at kappa-opioid receptors and at ORL1 receptors as well. The
      aim of our study was to examine whether the known stereoselective antagonism of
      Mr 2266 at kappa-opioid receptors also extends to ORL1 receptors. In mouse brain
      cortex membranes, the binding of the ORL1 receptor agonist [3H]nociceptin was
      equipotently inhibited by Mr 2266 and its enantiomer Mr 2267 (pK(i) 4.82 and
      5.14, respectively), whereas the binding of the kappa-opioid receptor agonist
      [3H]U-69,593 was inhibited by Mr 2266 more potently (pK(i) 9.11) than by its
      enantiomer Mr 2267 (pK(i)7.15). In mouse brain cortex slices preincubated with
      [3H]noradrenaline, the concentration-response curve of nociceptin for inhibition
      of the electrically evoked overflow of tritium was equipotently shifted to the
      right by Mr 2266 and Mr 2267 (pA2 5.77 and 5.64, respectively). On the other
      hand, the inhibitory effect of U-69,593 on the electrically evoked overflow of
      tritium in guinea-pig brain cortex slices preincubated with [3H]noradrenaline was
      more potently antagonized by Mr 2266 (pA2 8.81) than by Mr 2267 (pA2 7.15). These
      data show that the stereoselective antagonism of Mr 2266 at kappa-opioid
      receptors does not extend to ORL1 receptors.

PMID- 9933146
TI  - Differences in agonist-independent activity of 5-Ht2A and 5-HT2c receptors
      revealed by heterologous expression.
AB  - 5-Hydroxytryptamine 5-HT2A and 5-HT2C receptors share many properties, including
      a common ability to stimulate phospholipase C. Traditionally, this activation was
      thought to be initiated only after agonist binding, in accordance with the
      ternary complex model of receptor function. Recently, though, the 5-HT2C receptor
      was shown to deviate from this tenet by spontaneously isomerizing into the active
      receptor state, thereby activating G proteins in the absence of agonist. To
      determine if 5-HT2A receptors share this property of constitutive activity, 5
      HT2A and 5-HT2C receptor function was evaluated in transiently transfected NIH
      3T3 fibroblasts. In 3T3 cells expressing 5-HT2C receptors, agonist-independent
      phosphatidyl inositol hydrolysis was substantially elevated relative to mock
      transfected cells. In contrast, expression of the 5-HT2A receptor at the same
      density caused only a marginal increase in basal signaling. Control experiments
      in the current and previous papers establish that basal activity does not reflect
      contaminating serotonin. In addition, the magnitude of serotonin-induced
      signaling was the same in cells expressing either receptor, suggesting that the
      intrinsic ability of the two receptors to couple to G proteins is comparable.
      These data indicate that the 5-HT2A receptor has a much lower intrinsic ability
      to spontaneously adopt or maintain the active receptor conformation than does the
      closely related 5-HT2C receptor.

PMID- 9933147
TI  - Signaling via A2A adenosine receptor in four PC12 cell clones.
AB  - PC12 cells are genetically labile and so-called wild-type cells comprise multiple
      subclones. We have examined the A2A adenosine receptor signal transduction
      pathways in four such clones (denoted clones 1, 19, 21 and 27) of PC12 cells.
      Adenosine A2A, A2B and A1 receptor mRNAs were detected in all four clones by RT
      PCR, whereas no A3 receptor mRNA was found. A2A receptors were quantitated by
      radioligand binding using the antagonist radioligand [3H]SCH 58261 ([3H]-5-amino
      7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4 triazolo [1,5-c] pyrimidine).
      The Bmax was highest in clone 1 followed by clones 21, 19 and 27. Whereas the
      amount of G(i) protein appeared similar in all four clones, the amount of G(s)
      protein was higher in clones 21 and 27 than in the other two clones. Maximal
      responses to the non-selective adenosine analogue NECA (5'-N
      ethylcarboxamidoadenosine) were similar to those observed with the selective
      adenosine A2A receptor agonist CGS 21680 (2-[p-(2-carbonylethyl)
      phenylethylamino]-5'-N-ethylcarboxamidoadenosine), and were approximately equal
      in clones I and 21, but lower in clone 19 and very low in clone 27. For both
      compounds EC50 was significantly higher in clone 27 than in clone 1. In both
      clones the response to NECA could be competitively antagonized by a selective
      adenosine A2A antagonist, SCH 58261. The present results show that different
      clones of PC 12 cells differ widely in the cAMP increase induced by adenosine
      analogues and that this is due to differences in the amount of adenosine A2A
      receptor, G protein and effector. A large difference in receptor number resulted
      in differences in potency of an agonist.

PMID- 9933149
TI  - 5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes.
AB  - The effect of the selective r5-HT1B agonist 3-(1,2,5,6-tetrahydro)-4-pyridil-5
      pyrrolo [3,2-b] pyril-5-one (CP93,129) on the K(+)-evoked overflow of
      [3H]dopamine was studied in rat striatal synaptosomes loaded with [3H]dopamine.
      The aim of the study was to investigate the participation of 5-HT1B receptors in
      the serotonergic modulation of striatal dopaminergic transmission. The Ca2(+)
      dependent, tetrodotoxin-resistant K(+)-evoked overflow of [3H]dopamine was
      inhibited by CP93,129 (0.01-100 microM) in a concentration-dependent manner
      (IC50=1.8 microM; maximal inhibition by 35.5% of control). [+/-]8-OH-DPAT, a 5
      HT(1A) receptor agonist, [+/-]DOI, a 5-HT2 receptor agonist, and 2-methyl-5
      hydroxytryptamine, a 5-HT3 receptor agonist, at concentrations ranging from 0.01
      microM to 100 microM did not show any significant effect. Neither ketanserin (1
      microM and 5 microM), a selective 5-HT2/5-HT1D receptor antagonist, nor
      ondansetron (1 microM), a 5-HT3 receptor antagonist, changed the inhibitory
      effect of CP93,129. SB224289, GR55562, GR127935, isamoltane and metergoline,
      selective and non-selective 5-HT1B receptor antagonists, in contrast, used at a
      concentration of 1 microM, antagonized the inhibitory effect of CP93,129 (3
      microM and 10 microM). SB224289, a selective 5-HT1B receptor antagonist,
      inhibited the effect of CP93,129 in a concentration-dependent manner; the
      calculated K(i) value was 1.8 nM. Our results indicate that in rat striatal axon
      terminals the K(+)-evoked release of dopamine is regulated by the presynaptic 5
      HT1B heteroreceptors.

PMID- 9933148
TI  - Effects of retigabine (D-23129) on different patterns of epileptiform activity
      induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices.
AB  - The purpose of this study was to evaluate the effects of the new anticonvulsant
      drug N-(2-amino-4-[fluorobenzylaminol-phenyl) carbamic acid ethyl ester
      (retigabine, D-23129, ASTA Medica, Dresden, Germany) on different patterns of
      epileptiform activity induced by 4-aminopyridine (4AP) in rat entorhinal cortex
      hippocampal slices. Application of 4AP (100 microM) induced in entorhinal cortex
      two different types of epileptiform activities; seizure-like events (SLE) and
      interictal epileptiform discharges (IED). Bicuculline (10 microM) changed 4AP
      induced SLE and IED to recurrent epileptiform discharges (RED). IED were isolated
      after blockade of the SLE by glutamate receptor antagonists for alpha-amino-3
      hydroxy-5-methylisoxazole4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA)
      receptors, i.e. 1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzolflquinoxaline-7
      sulfonamide (NBQX, 10 microM) and 2-amino-5-phosphonovaleric acid (APV, 30
      microM). Anticonvulsant properties of retigabine were evaluated as effect on the
      frequency and amplitude of SLE, IED and RED. Retigabine suppressed all types of
      epileptiform events in a dose dependent and reversible manner. SLE were
      suppressed in 71.4 and 100% of slices by 5 and 10 microM, respectively. The
      frequency of IED was significantly reduced by 20 microM retigabine (40.9+/-24.5%)
      and IED were blocked completely by 50 microM retigabine. When IED were isolated
      by application of glutamate antagonists 20 microM retigabine was sufficient to
      block this activity completely. RED induced by combined application of
      bicuculline and 4AP were blocked in 71.4% of the tested slices with 100 microM
      retigabine. The frequency of the RED in the remaining slices was reduced by
      96.1+/-6.1%. We conclude that retigabine acts on a large variety of different
      epileptiform activities in temporal lobe structures that are known to develop
      readily pharmacoresistant seizures.

PMID- 9933151
TI  - High blood levels of nitric oxide in rats subjected to prolonged respiratory
      arrest and their modulation during adrenocorticotropin-induced resuscitation.
AB  - Anaesthetized rats, endotracheally intubated and mechanically ventilated with
      room air, were subjected to a 5-min period of asphyxia by turning off the
      ventilator. The ventilator was then turned back on and, simultaneously, the
      animals were treated with either the adrenocorticotropin fragment 1-24 [ACTH-(1
      24), 160 microg/kg in a volume of 1 ml/kg i.v.] or an equivalent volume of
      saline. Nitric oxide (NO)-haemoglobin formation was detected ex vivo in arterial
      blood by electron spin resonance spectrometry; arterial blood pressure,
      electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for a 60
      min observation period, or until prior death. During asphyxia, there was massive
      formation of NO (red cell concentrations 40-80 microM), associated with a
      dramatic fall in mean arterial pressure and pulse pressure, marked bradycardia
      and ECG signs of ischaemic damage, as well as an isoelectric EEG. Treatment with
      ACTH-(1-24) produced a prompt (within 15 min) and long-lasting drop in NO blood
      levels, associated with an almost immediate (within 1 min) restoration of
      cardiovascular function and with a more gradual recovery of EEG, which became
      normal after 3040 min; all parameters remained stable throughout the 60-min
      observation period. In saline-treated rats, on the other hand, there was a
      further increase in NO blood levels, as detected 3 min after treatment, and all
      died within 5-8 min. Moreover, pretreatment and treatment with S
      methylisothiourea sulphate (SMT, 3 mg/kg i.v.), a relatively specific inhibitor
      of inducible NO synthase, inhibited NO formation, but did not affect the
      mortality rate (100% within 5-8 min). The present results provide the first
      evidence that prolonged asphyxia is associated with high blood concentrations of
      NO, and that the life-saving effect of melanocortin peptides in severe hypoxic
      conditions is associated with a complete normalization of NO blood levels.
      However, the lack of SMT protection in this experimental model seems to rule out
      the possibility that the ACTH-(1-24)-induced resuscitation is due to an effect on
      NO overproduction.

PMID- 9933152
TI  - Na+-channel modulating effect of the inotropic compound S(-)BDF 9196 in human
      myocardium.
AB  - S(-)BDF 9196, the active enantiomer of racemic (+/-)BDF 9148, has been shown to
      increase force of contraction in myocardium from different species including
      humans. The present study aimed to investigate the mechanism of the positive
      inotropic action of the active enantiomer S(-)BDF 9196 in human myocardium. In
      electrically driven human left ventricular papillary muscle strips (dilated
      cardiomyopathy, NYHA IV, cardiac transplantation, n=9), S(-)BDF 9196 increased
      force of contraction concentration-dependently. The maximal positive inotropic
      effect remained unchanged after the addition of carbachol (1 mmol/l, indicating a
      cAMP-independent mode of action of S(-)BDF 9196. While [3H]ouabain binding in
      human myocardial membranes was not influenced by S(-)BDF 9196 up to 10
      micromol/l, the inward Na(+)-current in isolated human left ventricular myocytes
      was increased significantly by S(-)BDF 9196 (1 micromol/l, n=5). These results
      provide evidence that S(-)BDF 9196 increases force of contraction in human
      myocardium primarily by enhancing Na(+)-influx, while cAMP-dependent or
      Na(+),K(+)-ATPase blocking effects do not seem to play a role.

PMID- 9933150
TI  - Characterization of cannabinoid receptors coupled to vasorelaxation by
      endothelium-derived hyperpolarizing factor.
AB  - We have recently proposed that an endogenous cannabinoid may be an endothelium
      derived hyperpolarizing factor (EDHF), and we have now characterized the
      cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxations to
      carbachol (ED50=3.26+/-0.57 nmol; the maximum relaxation, Rmax = 87.0+/-2.5%)
      were opposed by the selective cannabinoid CB1 antagonist, LY320135: at 2 microM
      ED50 for carbachol was 10.4+/-2.6 nmol and Rmax was 66.9+/-6.2%, at 10 microM
      ED50 was 15.9+/-4.0 nmol and Rmax was 34.0+/-4.3%. However, these responses were
      unaffected by another putative CB1 ligand, AM630 (10 microM), or a CB2 selective
      antagonist, SR 144528 (100 nM-1 microM). None of the antagonists influenced
      vasorelaxation to either the potassium channel activator levcromakalim or sodium
      nitroprusside. Coupled to our previous observation that the CB1 receptor
      antagonist SR141716A opposes EDHF-mediated relaxation, the present observations
      point to the involvement of a cannabinoid receptor, which may be CB or CB1-like,
      in EDHF-mediated vasorelaxation.

PMID- 9933153
TI  - Defaecation, intestinal fluid accumulation and motility in rodents: implications
      of cannabinoid CB1 receptors.
AB  - We have studied the effect of SR141716A (0.1-5 mg/kg, i.p.), a cannabinoid CB,
      receptor antagonist, and WIN (0.1-5 mg/kg, i.p.), a cannabinoid receptor agonist,
      on acute defaecation and gastrointestinal transit in mice and on intraluminal
      fluid accumulation in the rat small intestine. SR141716A increased while WIN
      55,212-2 decreased defaecation, gastrointestinal transit and fluid accumulation.
      A per se non-effective dose of SR141716A (0.3 mg/kg) counteracted the inhibitory
      effect of WIN 55,212-2 (1 mg/kg) on gastrointestinal functions studied. The
      effect of SR 141716 on both intestinal fluid accumulation in rats and
      gastrointestinal transit in mice was inhibited by atropine (1 mg/kg, i.p.), but
      not by hexamethonium (1 mg/kg, s.c.), SR140333 (20 microg/kg, i.p.) or SR48968
      (20 microg/kg, i.p.), antagonists of NK1 and NK2 receptors, respectively. These
      results suggest that intestinal fluid accumulation and motility are inhibited by
      endogenous cannabinoid(s) acting at the cannabinoid CB1 receptors. This effect
      may be mediated by mechanisms involving muscarinic cholinoceptors.

PMID- 9933154
TI  - Different tachykinin receptors mediate chloride secretion in the distal colon
      through activation of submucosal neurones.
AB  - We investigated the role of tachykinin receptor subtypes on secretory responses
      in the guinea-pig distal colon using Ussing chamber experiments and intracellular
      recordings from submucosal neurones. Choline acetyltransferase (ChAT) and
      vasoactive intestinal polypeptide (VIP) were demonstrated in submucosal neurones
      by immunohistochemistry. In Ussing chamber experiments substance P (SP), the NK1
      receptor agonist [SAR9,Met(O2)11]-SP and the NK-3-receptor agonist (MePhe7)-NKB
      increased dose-dependently short-circuit currents. The NK-2-receptor agonist
      (betaAla8)-NKA(4-10) had no effect. Responses to 1-100 nM SP, [(SAR9,Met(O2)11]
      SP and (MePhe7)-NKB were tetrodotoxin-sensitive but hexamethonium-insensitive.
      While (MePhe7)-NKB-responses were atropine-sensitive at all concentrations, the
      atropine sensitivity of the secretory responses to SP and [SAR9,Met(O2)11]-SP
      dramatically decreased with increasing concentrations. [SAR9,Met(O2)11]-SP and
      (MePhe7)-NKB effects were blocked by the selective NK-I and NK-3 antagonists CP
      99,994-1 (1 microM) and SR 142801 (1 microM), respectively. Combination of both
      antagonists blocked the SP-response. SR 142801 also suppressed the response to
      [SAR9,Met(O2)11]-SP. Desensitization with [SAR9,Met(O2)11]-SP significantly
      decreased (MePhe7)-NKB-responses but not vice versa. In intracellular recordings
      90% of submucosal neurones were activated by both ISAR9,Met(O2)11]-SP and
      (MePhe7)-NKB as indicated by membrane depolarisation and enhanced spike
      discharge. These effects were tetrodotoxin-resistant and potentiated by atropine.
      NK-1-and NK-3-mediated responses occurred equally in ChAT-positive and in VIP
      positive neurones. The results suggest the importance of NK-1- and NK-3-receptors
      on cholinergic and non-cholinergic submucosal neurones for secretory processes in
      the guinea-pig distal colon.

PMID- 9933156
TI  - Solar wind outflow and the chromospheric magnetic network 
AB  - Observations of outflow velocities in coronal holes (regions of open coronal
      magnetic field) have recently been obtained with the Solar and Heliospheric
      Observatory (SOHO) spacecraft. Velocity maps of Ne7+ from its bright resonance
      line at 770 angstroms, formed at the base of the corona, show a relationship
      between outflow velocity and chromospheric magnetic network structure, suggesting
      that the solar wind is rooted at its base to this structure, emanating from
      localized regions along boundaries and boundary intersections of magnetic network
      cells. This apparent relation to the chromospheric magnetic network and the
      relatively large outflow velocity signatures will improve understanding of the
      complex structure and dynamics at the base of the corona and the source region of
      the solar wind.

PMID- 9933157
TI  - Asymmetric scattering of polarized electrons by organized organic films of chiral
      molecules 
AB  - Electron transmission experiments demonstrate a large asymmetry in the scattering
      probability of polarized electrons by thin organized films of chiral molecules.
      This large asymmetry results from the interaction of the electron's wavefunction
      with many scatterers (molecules) in the organized monolayer structure and
      represents a manifestation of quantum interference on the scale of supramolecular
      lengths.

PMID- 9933155
TI  - Population biology, evolution, and infectious disease: convergence and synthesis.
AB  - Traditionally, the interest of population and evolutionary biologists in
      infectious diseases has been almost exclusively in their role as agents of
      natural selection in higher organisms. Recently, this interest has expanded to
      include the genetic structure and evolution of microparasite populations, the
      mechanisms of pathogenesis and the immune response, and the population biology,
      ecology, and evolutionary consequences of medical and public health
      interventions. This article describes recent work in these areas, emphasizing the
      ways in which quantitative, population-biological approaches have been
      contributing to the understanding of infectious disease and the design and
      evaluation of interventions for their treatment and prevention.

PMID- 9933158
TI  - Self-assembly of flat nanodiscs in salt-free catanionic surfactant solutions 
AB  - Discs of finite size are a very rare form of stable surfactant self-assembly. It
      is shown that mixing of two oppositely charged single-chain surfactants can
      produce rigid nanodiscs as well as swollen lamellar liquid crystals with frozen
      bilayers. The crucial requirement for obtaining nanodisc self-assembly is the use
      of H+ and OH- as counterions. These counterions then form water and lower the
      conductivity to 10 microsiemens per centimeter. In the case of cationic component
      excess, a dilute solution of nanodiscs is in thermodynamic equilibrium with a
      lamellar phase. The diameter of the cationic nanodiscs is continuously adjustable
      from a few micrometers to 30 nanometers, with the positive charge located mainly
      around the edges.

PMID- 9933159
TI  - A tenuous carbon dioxide atmosphere on Jupiter's moon Callisto.
AB  - An off-limb scan of Callisto was conducted by the Galileo near-infrared mapping
      spectrometer to search for a carbon dioxide atmosphere. Airglow in the carbon
      dioxide nu3 band was observed up to 100 kilometers above the surface and
      indicates the presence of a tenuous carbon dioxide atmosphere with surface
      pressure of 7.5 x 10(-12) bar and a temperature of about 150 kelvin, close to the
      surface temperature. A lifetime on the order of 4 years is suggested, based on
      photoionization and magnetospheric sweeping. Either the atmosphere is transient
      and was formed recently or some process is currently supplying carbon dioxide to
      the atmosphere.

PMID- 9933160
TI  - Low-voltage organic transistors on plastic comprising high-dielectric constant
      gate insulators 
AB  - The gate bias dependence of the field-effect mobility in pentacene-based
      insulated gate field-effect transistors (IGFETs) was interpreted on the basis of
      the interaction of charge carriers with localized trap levels in the band gap.
      This understanding was used to design and fabricate IGFETs with mobility of more
      than 0.3 square centimeter per volt per second and current modulation of 10(5),
      with the use of amorphous metal oxide gate insulators. These values were obtained
      at operating voltage ranges as low as 5 volts, which are much smaller than
      previously reported results. An all-room-temperature fabrication process sequence
      was used, which enabled the demonstration of high-performance organic IGFETs on
      transparent plastic substrates, at low operating voltages for organic devices.

PMID- 9933161
TI  - Ancient diets, ecology, and extinction of 5-million-year-Old horses from florida 
AB  - Six sympatric species of 5-million-year-old (late Hemphillian) horses from
      Florida existed during a time of major global change and extinction in
      terrestrial ecosystems. Traditionally, these horses were interpreted to have fed
      on abrasive grasses because of their high-crowned teeth. However, carbon isotopic
      and tooth microwear data indicate that these horses were not all C4 grazers but
      also included mixed feeders and C3 browsers. The late Hemphillian Florida sister
      species of the modern genus Equus was principally a browser, unlike the grazing
      diet of modern equids. Late Hemphillian horse extinctions in Florida involved two
      grazing and one browsing species.

PMID- 9933162
TI  - 16O excesses in olivine inclusions in Yamato-86009 and Murchison chondrites and
      their relation to CAIs.
AB  - In situ ion microprobe analyses of oxygen isotopes in Yamato-86009 and Murchison
      chondrites show that they contain abundant olivine-rich inclusions that have
      large oxygen-16 (16O) excesses, similar to those in spinel grains in calcium
      aluminium-rich inclusions in Allende and other carbonaceous chondrites. The
      existence of 16O-enriched olivine-rich inclusions suggests that oxygen isotopic
      anomalies were more extensive in the early solar system than was previously
      thought and that their origin may be attributed to a nebular chemical process
      rather than to an unidentified 16O-rich carrier of presolar origin.

PMID- 9933163
TI  - Elongation of oligopeptides in a simulated submarine hydrothermal system.
AB  - Oligomerization of a peptide was attempted in a flow reactor that simulated a
      submarine hydrothermal system. When fluid containing glycine repeatedly
      circulated through the hot and cold regions in the reactor, oligopeptides were
      made from glycine. When divalent ions (such as copper ions) were added under
      acidic conditions, oligoglycine was elongated up to hexaglycine. This observation
      suggests that prebiotic monomers could have oligomerized in the vicinity of
      submarine hydrothermal vents on primitive Earth.

PMID- 9933164
TI  - Oligomeric structure of the human EphB2 receptor SAM domain.
AB  - The sterile alpha motif (SAM) domain is a protein interaction module that is
      present in diverse signal-transducing proteins. SAM domains are known to form
      homo- and hetero-oligomers. The crystal structure of the SAM domain from an Eph
      receptor tyrosine kinase, EphB2, reveals two large interfaces. In one interface,
      adjacent monomers exchange amino-terminal peptides that insert into a hydrophobic
      groove on each neighbor. A second interface is composed of the carboxyl-terminal
      helix and a nearby loop. A possible oligomer, constructed from a combination of
      these binding modes, may provide a platform for the formation of larger protein
      complexes.

PMID- 9933166
TI  - Widespread iron limitation of phytoplankton in the south pacific ocean 
AB  - Diel fluorescence patterns were discovered in phytoplankton sampled over 7000
      kilometers of the South Pacific Ocean that appear indicative of iron-limiting
      growth conditions. These patterns were rapidly lost after in situ iron enrichment
      and were not observed during a 15,000-kilometer transect in the Atlantic Ocean
      where iron concentrations are relatively high. Laboratory studies of marine
      Synechococcus sp. indicated that the patterns in the South Pacific are a unique
      manifestation of iron limitation on the fluorescence signature of state
      transitions. Results suggest that primary productivity is iron limited not only
      throughout the equatorial Pacific but also over much of the vast South Pacific
      gyre.

PMID- 9933165
TI  - Single-channel recording of a store-operated Ca2+ channel in Jurkat T
      lymphocytes.
AB  - In T lymphocytes, a store-operated calcium ion (Ca2+) entry mechanism termed the
      calcium release-activated Ca2+ channel (CRAC channel) underlies the sustained or
      oscillatory intracellular calcium concentration signal required for interleukin-2
      gene expression and cell proliferation. The use of sodium ions as a current
      carrier enabled single-channel recordings of CRAC channels during activation,
      inactivation, and blockade of current in the presence of divalent cations. A
      large conductance of 36 to 40 picosiemens indicates that 100 to 400 CRAC channels
      are present in T lymphocytes.

PMID- 9933167
TI  - The dynamics of zooxanthellae populations: A long-term study in the field 
AB  - Coral bleaching characterized by the expulsion of symbiotic algae (zooxanthellae)
      is an increasing problem worldwide. Global warming has been implicated as one
      cause, but the phenomenon cannot be fully comprehended without an understanding
      of the variability of zooxanthellae populations in field conditions. Results from
      a 6-year field study are presented, providing evidence of density regulation but
      also of large variability in the zooxanthellae population with regular episodes
      of very low densities. These bleaching events are likely to be part of a constant
      variability in zooxanthellae density caused by environmental fluctuations
      superimposed on a strong seasonal cycle in abundance.

PMID- 9933168
TI  - Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on
      CXCR4.
AB  - Stem cell homing and repopulation are not well understood. The chemokine stromal
      cell-derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical
      for murine bone marrow engraftment by human severe combined immunodeficient
      (SCID) repopulating stem cells. Treatment of human cells with antibodies to CXCR4
      prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34+CD38
      /low cells correlated with in vivo engraftment and stem cell function. Stem cell
      factor and interleukin-6 induced CXCR4 expression on CD34+ cells, which
      potentiated migration to SDF-1 and engraftment in primary and secondary
      transplanted mice. Thus, up-regulation of CXCR4 expression may be useful for
      improving engraftment of repopulating stem cells in clinical transplantation.

PMID- 9933169
TI  - CD3- and CD28-dependent induction of PDE7 required for T cell activation.
AB  - Costimulation of both the CD3 and CD28 receptors is essential for T cell
      activation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific
      phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation.
      Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2
      expression, and increased proliferation. Selectively reducing PDE7 expression
      with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition
      was reversed by blocking the cAMP signaling pathways that operate through cAMP
      dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression
      of PKA activity is required for T cell activation, and inhibition of PDE7 could
      be an approach to treating T cell-dependent disorders.

PMID- 9933170
TI  - Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in
      Xenopus egg extracts.
AB  - The abnormally high number of centrosomes found in many human tumor cells can
      lead directly to aneuploidy and genomic instability through the formation of
      multipolar mitotic spindles. To facilitate investigation of the mechanisms that
      control centrosome reproduction, a frog egg extract arrested in S phase of the
      cell cycle that supported repeated assembly of daughter centrosomes was
      developed. Multiple rounds of centrosome reproduction were blocked by selective
      inactivation of cyclin-dependent kinase 2-cyclin E (Cdk2-E) and were restored by
      addition of purified Cdk2-E. Confocal immunomicroscopy revealed that cyclin E was
      localized at the centrosome. These results demonstrate that Cdk2-E activity is
      required for centrosome duplication during S phase and suggest a mechanism that
      could coordinate centrosome reproduction with cycles of DNA synthesis and
      mitosis.

PMID- 9933171
TI  - Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for
      virulence.
AB  - Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe human
      skin disease that occurs primarily in Africa and Australia. Infection with M.
      ulcerans results in persistent severe necrosis without an acute inflammatory
      response. The presence of histopathological changes distant from the site of
      infection suggested that pathogenesis might be toxin mediated. A polyketide
      derived macrolide designated mycolactone was isolated that causes cytopathicity
      and cell cycle arrest in cultured L929 murine fibroblasts. Intradermal
      inoculation of purified toxin into guinea pigs produced a lesion similar to that
      of Buruli ulcer in humans. This toxin may represent one of a family of virulence
      factors associated with pathology in mycobacterial diseases such as leprosy and
      tuberculosis.

PMID- 9933173
TI  - The genomic challenge.

PMID- 9933172
TI  - Control of viremia in simian immunodeficiency virus infection by CD8+
      lymphocytes.
AB  - Clinical evidence suggests that cellular immunity is involved in controlling
      human immunodeficiency virus-1 (HIV-1) replication. An animal model of acquired
      immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)
      infected rhesus monkey, was used to show that virus replication is not controlled
      in monkeys depleted of CD8+ lymphocytes during primary SIV infection. Eliminating
      CD8+ lymphocytes from monkeys during chronic SIV infection resulted in a rapid
      and marked increase in viremia that was again suppressed coincident with the
      reappearance of SIV-specific CD8+ T cells. These results confirm the importance
      of cell-mediated immunity in controlling HIV-1 infection and support the
      exploration of vaccination approaches for preventing infection that will elicit
      these immune responses.

PMID- 9933174
TI  - Emergency contraception: is it time to change method?

PMID- 9933175
TI  - Benign prostatic hyperplasia.

PMID- 9933176
TI  - Changing practice in growth monitoring.

PMID- 9933177
TI  - Evidence based mergers?

PMID- 9933178
TI  - The impact of new technologies in medicine. Call for papers 

PMID- 9933180
TI  - UK nurses awarded large pay rise 

PMID- 9933179
TI  - Bill paves way for new round of NHS changes.

PMID- 9933181
TI  - Bristol doctor refused access to confidential GMC notes.

PMID- 9933182
TI  - Senegal outlaws female genital mutilation.

PMID- 9933184
TI  - Heart attack patients do better in America's "best" hospitals 

PMID- 9933185
TI  - UK doctors' revalidation should be linked to registration 

PMID- 9933183
TI  - Netherlands sets up euthanasia advisory body.

PMID- 9933186
TI  - Inquiry says surgeons should stop operating if patient dies.

PMID- 9933188
TI  - More doctors and donors needed for transplantation in the UK.

PMID- 9933187
TI  - UN assesses aid needed for Colombian earthquake zone.

PMID- 9933189
TI  - Researchers implant tissue engineered bladders 

PMID- 9933190
TI  - Waiting times in British casualty departments remain too long.

PMID- 9933191
TI  - UK plan for food standards agency 

PMID- 9933192
TI  - Toronto research funding dispute 

PMID- 9933193
TI  - European observatory will promote better health policy 165.

PMID- 9933194
TI  - What are the symptoms of varicose veins? Edinburgh vein study cross sectional
      population survey.
AB  - OBJECTIVE: To define the relations between age, sex, lower limb symptoms, and the
      presence of trunk varicose veins on clinical examination. DESIGN: Cross sectional
      population study. SETTING: 12 general practices with catchment areas
      geographically and socioeconomically distributed throughout Edinburgh.
      PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867
      women) aged 18-64 selected from the computerised age-sex registers of
      participating practices. MAIN OUTCOME MEASURES: Self administered questionnaire
      on the presence of lower limb symptoms and physical examination to determine the
      presence and severity of varicose veins. RESULTS: Women were significantly more
      likely than men to report lower limb symptoms such as heaviness or tension,
      swelling, aching, restless legs, cramps, and itching. The prevalence of symptoms
      tended to increase with age in both sexes. In men, only itching was significantly
      related to the presence and severity of trunk varices (linear test for trend,
      P=0.011). In women there was a significant relation between trunk varices and the
      symptoms of heaviness or tension (P</=0.001), aching (P</=0.001), and itching
      (P</=0.005). However, the level of agreement between the presence of symptoms and
      trunk varices was too low to be of clinical value, especially in men.
      CONCLUSIONS: Even in the presence of trunk varices, most lower limb symptoms
      probably have a non-venous cause. Surgical extirpation of trunk varices is
      unlikely to ameliorate such symptoms in most patients.

PMID- 9933196
TI  - An annoying sound 

PMID- 9933197
TI  - National cross sectional study of detection of congenital and infantile cataract
      in the United Kingdom: role of childhood screening and surveillance. The British
      Congenital Cataract Interest Group.
AB  - OBJECTIVES: To determine the mode of detection and timing of ophthalmic
      assessment of a nationally representative group of children with congenital and
      infantile cataract. DESIGN: Cross sectional study. SETTING: United Kingdom.
      SUBJECTS: All children born in the United Kingdom and aged 15 years or under in
      whom congenital or infantile cataract was newly diagnosed between October 1995
      and September 1996. MAIN OUTCOME MEASURES: Proportion of cases detected through
      routine ocular examination and proportion assessed by an ophthalmologist by 3
      months and 1 year of age. RESULTS: Data were complete for 235 (95%) of 248
      children identified. Of these, 83 (35%) were detected at the routine newborn
      examination and 30 (12%) at the 6-8 week examination; 82 children presented
      symptomatically. 137 (57%) children had been assessed by an ophthalmologist by
      the age of 3 months but 78 (33%) were not examined until after 1 year of age. In
      91 cases the child's carers suspected an eye defect before cataract was
      diagnosed. CONCLUSIONS: A substantial proportion of children with congenital and
      infantile cataract are not diagnosed by 3 months of age, although routine ocular
      examination of all newborn and young infants is recommended nationally.
      Strategies to achieve earlier detection through screening and surveillance are
      required.

PMID- 9933195
TI  - Withdrawing low risk women from cervical screening programmes: mathematical
      modelling study.
AB  - OBJECTIVE: To evaluate the impact of policies for removing women before the
      recommended age of 64 from screening programmes for cervical cancer in the United
      Kingdom. DESIGN: A mathematical model of the clinical course of precancerous
      lesions which accounts for the influence of infection with the human
      papillomavirus, the effects of screening on the progression of disease, and the
      accuracy of the testing procedures. Two policies are compared: one in which women
      are withdrawn from the programme if their current smear is negative and they have
      a recent history of regular, negative results and one in which women are
      withdrawn if their current smear test is negative and a simultaneous test is
      negative for exposure to high risk types of human papillomavirus. SETTING: United
      Kingdom cervical screening programme. MAIN OUTCOME MEASURES: The incidence of
      invasive cervical cancer and the use of resources. RESULTS: Early withdrawal of
      selected women from the programme is predicted to give rise to resource savings
      of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from
      age 50, the youngest age considered in the study. An increase in the incidence of
      invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted.
      Testing for human papillomavirus infection to determine which women should be
      withdrawn from the programme makes little difference to outcome. CONCLUSIONS:
      This model systematically analyses the consequences of screening options using
      available data and the clinical course of precancerous lesions. If further audit
      studies confirm the model's forecasts, a policy of early withdrawal might be
      considered. This would be likely to release substantial resources which could be
      channelled into other aspects of health care or may be more effectively used
      within the cervical screening programme to counteract the possible increase in
      cancer incidence that early withdrawal might bring.

PMID- 9933198
TI  - Comparison of residential and nursing home care before and after the 1993
      community care policy.

PMID- 9933200
TI  - Mind over matter 

PMID- 9933199
TI  - Laterality of lower limb amputation in diabetic patients: retrospective audit.

PMID- 9933203
TI  - Homogenous/homogeneous 

PMID- 9933201
TI  - Prevalence and clinical characteristics of left ventricular dysfunction among
      elderly patients in general practice setting: cross sectional survey.
AB  - OBJECTIVE: To assess the prevalence and clinical characteristics of left
      ventricular dysfunction among elderly patients in the general practice setting by
      echocardiographic assessment of ventricular function. DESIGN: Cross sectional
      survey. SETTING: Four centre general practice in Poole, Dorset. SUBJECTS: 817
      elderly patients aged 70-84 years. MAIN OUTCOMES: Echocardiographic assessment of
      left ventricular systolic function including measurement of ejection fraction by
      biplane summation method where possible, clinical symptoms, and signs of left
      ventricular dysfunction. RESULTS: The overall prevalence of left ventricular
      systolic dysfunction was 7.5% (95% confidence interval 5.8% to 9.5%); mild
      dysfunction (5.0%) was considerably more prevalent than moderate (1.6%) or severe
      dysfunction (0.7%). Measurement of ejection fraction was possible in 82% of
      patients (n=667): in patients categorised as having mild, moderate, or severe
      dysfunction, the mean ejection fraction was 48% (SD 12.0), 38% (8.1), and 26%
      (7.9) respectively. At all ages the prevalence was much higher in men than in
      women (odds ratio 5.1, 95% confidence interval 2.6 to 10.1). No clinical symptom
      or sign was both sensitive and specific. In around half the patients with
      ventricular dysfunction (52%, 32/61) heart failure had not been previously
      diagnosed. CONCLUSIONS: Unrecognised left ventricular dysfunction is a common
      problem in elderly patients in the general practice setting. Appropriate
      treatment with angiotensin converting enzyme inhibitors has the potential to
      reduce hospitalisation and mortality in these patients, but diagnosis should not
      be based on clinical history and examination alone. Screening is feasible in
      general practice, but it should not be implemented until the optimum method of
      identifying left ventricular dysfunction is clarified, and the cost effectiveness
      of screening has been shown.

PMID- 9933202
TI  - Patients' perceptions of medical explanations for somatisation disorders:
      qualitative analysis.
AB  - OBJECTIVES: To describe, from the perspective of patients, distinguishing
      features of doctors' attempts to explain the symptoms of somatisation disorders.
      DESIGN: Qualitative analysis of verbatim records of interviews in which patients
      recounted doctors' explanations of their symptoms. SETTING: Patients with
      persistent somatising symptoms referred from general practices in Liverpool and
      St Helens and Knowsley were interviewed before entry into a treatment programme.
      SUBJECTS: 228 of 324 patients referred were interviewed. Initial interviews were
      used to develop the process and technique, and the final analysis was based on a
      subsample of 68 records, randomly chosen from the transcripts of 188 subjects who
      were interviewed subsequently. RESULTS: Doctors' explanations were often at odds
      with the patients' own thinking. Analysis showed that medical explanations could
      be grouped into one of three categories, defined by the patients' perceptions.
      Most explanations were experienced as rejecting the reality of the symptoms. An
      intermediate category comprised explanations that were viewed as colluding, in
      which the doctor acquiesced with the patients' own biomedical theories. However,
      a few explanations were perceived by patients as tangible, exculpating, and
      involving. These explanations were experienced by patients as satisfying and
      empowering. CONCLUSIONS: Patients with somatisation disorders feel satisfied and
      empowered by medical explanations that are tangible, exculpating, and involving.
      Empowering explanations could improve these patients' wellbeing and help to
      reduce the high demands they make on health services.

PMID- 9933204
TI  - NHSnet-learning from academia.

PMID- 9933205
TI  - Fortnightly review: modern drug treatment of chronic asthma.

PMID- 9933207
TI  - Spoken words losing their identity 

PMID- 9933206
TI  - Evidence based case report: treatment for head lice.

PMID- 9933208
TI  - ABC of sexual health: erectile dysfunction.

PMID- 9933209
TI  - Edward Jenner's inquiry after 200 years 

PMID- 9933210
TI  - Clinical guidelines-the hidden costs.

PMID- 9933211
TI  - Postmortem movements 

PMID- 9933212
TI  - JAMA's editor sacked. World medical journal editors should establish an award for
      editorial integrity in Lundberg's name.

PMID- 9933213
TI  - Teachers should aim to be stimulating rather than entertaining.

PMID- 9933214
TI  - Clinicians and epidemiologists view crude death rates differently.

PMID- 9933215
TI  - Misusers may receive methadone from drug centres and GPs simultaneously.

PMID- 9933216
TI  - BMA's gold medal award to the president of the South African Medical association.
      Is this a travesty?

PMID- 9933217
TI  - More extensive analysis is needed when assessing facial structure in SIDS.

PMID- 9933218
TI  - Alcohol consumption is not related to fertility in Italian women.

PMID- 9933219
TI  - NHS breast screening programme. Both extended age range and reduced screening
      interval are needed.

PMID- 9933220
TI  - Some American driving licences double as organ donor cards.

PMID- 9933221
TI  - Opt out registers for organ donation have existed in Belgium since 1987.

PMID- 9933222
TI  - Rate of carotid endarterectomy in Wessex might already be higher than necessary.

PMID- 9933223
TI  - Link between breast cancer and ATM gene is strong.

PMID- 9933225
TI  - John norman agate 

PMID- 9933224
TI  - Minerva should not review retrospective audits.

PMID- 9933227
TI  - Addicted 

PMID- 9933226
TI  - BMA ends link with healthcall 

PMID- 9933228
TI  - Evaluating health promotion 

PMID- 9933230
TI  - On-the-Job training for physicians 

PMID- 9933229
TI  - The spine and medical negligence 

PMID- 9933231
TI  - Elsie inglis 

PMID- 9933233
TI  - Website of the week 

PMID- 9933232
TI  - George falls for bill 

PMID- 9933234
TI  - Should we accept all comers? 

PMID- 9933235
TI  - In which we served 

PMID- 9933237
TI  - Leg symptoms do not correlate with varicose veins 

PMID- 9933236
TI  - Knowing when not to operate 

PMID- 9933238
TI  - Modelling is useful in evaluating early withdrawal of women from smear test
      programmes 

PMID- 9933239
TI  - UK screening for congenital cataracts needs improving 

PMID- 9933240
TI  - Left ventricular dysfunction is common but difficult to detect 

PMID- 9933241
TI  - Patients with somatisation disorders need considered explanations 

PMID- 9933242
TI  - Community care act has targeted care better 

PMID- 9933243
TI  - HIRA, a DiGeorge syndrome candidate gene, is required for cardiac outflow tract
      septation.
AB  - DiGeorge syndrome (DGS) is a congenital disease characterized by defects in
      organs and tissues that depend on contributions by cell populations derived from
      neural crest for proper development. A number of candidate genes that lie within
      the q11 region of chromosome 22 commonly deleted in DGS patients have been
      identified. Orthologues of the DGS candidate gene HIRA are expressed in the
      neural crest and in neural crest-derived tissues in both chick and mouse embryos.
      By exposing a portion of the premigratory chick neural crest to phosphorothioate
      end-protected antisense oligonucleotides, ex ovo, followed by orthotopic
      backtransplantation to the untreated embryos, we have shown that the functional
      attenuation of cHIRA in the chick cardiac neural crest results in a significantly
      increased incidence of persistent truncus arteriosus, a phenotypic change
      characteristic of DGS, but does not affect the repatterning aortic arch arteries,
      the ventricular function, or the alignment of the outflow tract.

PMID- 9933244
TI  - Establishment of beta-adrenergic modulation of L-type Ca2+ current in the early
      stages of cardiomyocyte development.
AB  - beta-Adrenergic modulation of the L-type Ca2+ current (ICaL) was characterized
      for different developmental stages in murine embryonic stem cell-derived
      cardiomyocytes using the whole-cell patch-clamp technique at 37 degreesC.
      Cardiomyocytes first appeared in embryonic stem cell-derived embryoid bodies
      grown for 7 days (7d). ICaL was insensitive to isoproterenol, forskolin, and 8
      bromo-cAMP in very early developmental stage (VEDS) cardiomyocytes (from 7+1d to
      7+2d) but highly stimulated by these substances in late developmental stage (LDS)
      cardiomyocytes (from 7+9d to 7+12d), indicating that all signaling cascade
      components became functionally coupled during development. In early developmental
      stage (EDS) cells (from 7+3d to 7+5d), the stimulatory response to forskolin and
      8-bromo-cAMP was relatively weak. The forskolin effect was strongly augmented by
      ATP-gamma-S. At this stage, basal ICaL was stimulated by the nonselective
      phosphodiesterase (PDE) inhibitor isobutylmethylxanthine, by PDE inhibitors
      selective for the PDE II, III, and IV isoforms, as well as by the phosphatase
      inhibitor okadaic acid. Stimulation of ICaL by the catalytic subunit of the cAMP
      dependent protein kinase A (PKA) was found to be similar (about 3 times)
      throughout development and in adult mouse ventricular cardiomyocytes, indicating
      that no structural changes of the Ca2+ channel related to phosphorylation
      occurred during development. ICaL was stimulated by isoproterenol in the presence
      of a PKA inhibitor and GTP-gamma-S in LDS but not VEDS cardiomyocytes, suggesting
      the development of a membrane-delimited stimulatory pathway mediated through the
      stimulatory GTP binding protein, Gs. We conclude that uncoupling and/or low
      expression of Gs protein accounted for the ICaL insensitivity to beta-adrenergic
      stimulation in VEDS cardiomyocytes. Furthermore, in EDS cells at the 7+4d stage,
      the reduced beta-adrenergic response is due, at least in part, to high intrinsic
      PDE and phosphatase activities.

PMID- 9933245
TI  - Replacement by homologous recombination of the minK gene with lacZ reveals
      restriction of minK expression to the mouse cardiac conduction system.
AB  - The minK gene encodes a 129-amino acid peptide the expression of which modulates
      function of cardiac delayed rectifier currents (IKr and IKs), and mutations in
      minK are now recognized as one cause of the congenital long-QT syndrome. We have
      generated minK-deficient mice in which the bacterial lacZ gene has been
      substituted for the minK coding region such that beta-galactosidase expression is
      controlled by endogenous minK regulatory elements. In cardiac myocytes isolated
      from wild-type neonatal mice, IKs is rarely recorded, while IKr is common. In
      minK (-/-) myocytes, IKs is absent and IKr is significantly reduced and its
      deactivation slowed; these results further support a role for minK in modulating
      both IKs and IKr. Despite these changes, ECGs in (+/+) and (-/-) animals are no
      different at adult and at neonatal stages. ECG responses to isoproterenol are
      also similar in the 2 groups. beta-Galactosidase staining in postnatal minK (-/-)
      hearts is highly restricted, to the sinus-node region, caudal atrial septum, and
      proximal conducting system. Moreover, as early as embryonal day 11, segmentally
      restricted beta-galactosidase expression is observed in the portions of the
      sinoatrial and atrioventricular junctions that are thought to give rise to the
      conducting system, thereby implicating minK expression as an early event in
      conduction system development. More generally, the restricted nature of minK
      expression in the mouse heart suggests species-specific roles of this gene
      product in mediating the electrophysiological properties of the heart.

PMID- 9933246
TI  - A novel mechanism of anode-break stimulation predicted by bidomain modeling.
AB  - -Anodal stimulation by external pacemakers has been explained on the basis of
      bidomain models of cardiac tissue. Bidomain models predict that anodal stimuli
      will hyperpolarize the underlying tissue while adjacent regions become
      depolarized (virtual cathodes), initiating excitation. We investigated the
      contribution of active cellular properties to anode-break stimulation. A bidomain
      model was implemented in which each cell contained realistic ionic currents,
      including those recruited by hyperpolarization. Simulations reveal that anode
      break excitation can originate at the site of stimulation itself and not only
      from adjacent regions of induced depolarization. The threshold for initiating
      excitation at the site of stimulation is lower than that for stimulation
      initiating from adjacent depolarized regions. Thus, incorporation of active
      cellular properties into a bidomain model predicts a novel mechanism for anode
      break stimulation of the heart. The results will improve our understanding of
      anodal pacing and its risks and benefits in patients.

PMID- 9933247
TI  - Swelling-activated chloride current is persistently activated in ventricular
      myocytes from dogs with tachycardia-induced congestive heart failure.
AB  - The hypothesis that cellular hypertrophy in congestive heart failure (CHF)
      modulates mechanosensitive (ie, swelling- or stretch-activated) anion channels
      was tested. Digital video microscopy and amphotericin-perforated-patch voltage
      clamp were used to measure cell volume and ion currents in ventricular myocytes
      isolated from normal dogs and dogs with rapid ventricular pacing-induced CHF. In
      normal myocytes, osmotic swelling in 0.9T to 0.6T solution (T, relative
      osmolarity; isosmotic solution, 296 mOsmol/L) was required to elicit ICl,swell,
      an outwardly rectifying swelling-activated Cl- current that reversed near -33 mV
      and was inhibited by 1 mmol/L 9-anthracene carboxylic acid (9AC), an anion
      channel blocker. Block of ICl,swell by 9AC simultaneously increased the volume of
      normal cells in hyposmotic solutions by up to 7%, but 9AC had no effect on volume
      in isosmotic or hyperosmotic solutions. In contrast, ICl,swell was persistently
      activated under isosmotic conditions in CHF myocytes, and 9AC increased cell
      volume by 9%. Osmotic shrinkage in 1.1T to 1.5T solution inhibited both ICl,swell
      and 9AC-induced cell swelling in CHF cells, whereas osmotic swelling only
      slightly increased ICl,swell. The current density for fully activated 9AC
      sensitive ICl,swell was 40% greater in CHF than normal myocytes. In both groups,
      9AC-sensitive current and 9AC-induced cell swelling were proportional with
      changes in osmolarity and 9AC concentration, and the effects of 9AC on current
      and volume were blocked by replacing bath Cl- with methanesulfonate. CHF thus
      altered the set point and magnitude of ICl,swell and resulted in its persistent
      activation. We previously observed analogous regulation of mechanosensitive
      cation channels in the same CHF model. Mechanosensitive anion and cation channels
      may contribute to the electrophysiological and contractile derangements in CHF
      and may be novel targets for therapy.

PMID- 9933248
TI  - Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin.
AB  - Calcification of vascular tissue is a common complication in aging,
      atherosclerosis, diabetes, renal failure, aortic stenosis, and prosthetic valve
      replacement. Osteopontin is a noncollagenous adhesive protein routinely found at
      sites of dystrophic calcification and synthesized at high levels by macrophages
      in calcified aortic valves and atherosclerotic plaques. In the present study, we
      have characterized the calcification of bovine aortic smooth muscle cell (BASMC)
      cultures in vitro and have studied the effects of exogenous osteopontin on
      mineral deposition. Induction of calcification in BASMC cultures was alkaline
      phosphatase-dependent and was characterized by a multilayer cell morphology.
      Mineral deposition occurred in the basal matrix of multilayered areas as
      indicated by von Kossa staining, and transmission electron microscopy and
      electron diffraction identified the mineral as apatite. Ultrastructural analysis
      of the cultures showed the presence of extracellular matrix vesicles, calcifying
      collagen fibrils, and nodular-type calcifications similar to those found in
      calcified heart valves and atherosclerotic plaques. Purified osteopontin (0.05 to
      5 microgram/mL) dose dependently inhibited calcification of BASMC cultures,
      whereas vitronectin and fibronectin had no effect. In contrast to the inhibitory
      mechanism of levamisole on mineral deposition, osteopontin did not inhibit
      alkaline phosphatase activity or reduce phosphorus levels in the culture medium.
      Addition of calcium to the cultures overcame the inhibitory effect of osteopontin
      on BASMC culture calcification and resulted in decreased levels of calcium in the
      culture medium and increased levels in the cell layer. Moreover, using high
      resolution, colloidal-gold immunocytochemistry, osteopontin was found intimately
      associated with growing apatite crystals. These data indicate that the effect of
      osteopontin, although calcium-dependent, was not mediated by simple calcium
      chelation but most likely by direct interaction of osteopontin with crystal
      surfaces. These studies suggest that BASMCs can be used to model vascular
      calcification in vitro and that soluble osteopontin released near sites of
      vascular calcification may represent an adaptive mechanism aimed at preventing
      vascular calcification.

PMID- 9933249
TI  - Vascular injury causes neointimal formation in angiotensin II type 1a receptor
      knockout mice.
AB  - Many studies using small-animal models suggest that angiotensin II (Ang II) plays
      an important role in neointimal formation after vascular injury. In the present
      study, we examined whether Ang II type 1 receptor (AT1)-mediated Ang II signaling
      is indispensable for the development of injury-induced neointimal formation using
      AT1a knockout (KO) mice. Reverse transcriptase-polymerase chain reaction analysis
      revealed that AT1 mRNA was not detectable in both uninjured and injured carotid
      arteries of KO mice, whereas the AT1 gene was expressed in uninjured carotid
      arteries of wild-type (WT) mice. At 14 days after injury, AT1 mRNA levels were
      increased by 1.5-fold in injured arteries of WT mice. Although AT2 mRNA was not
      detectable in uninjured arteries, expression of AT2 gene was induced in both
      animal groups at 2 weeks after injury. Vascular injury induced neointimal
      formation in KO mice as well as in WT mice. There were no significant differences
      between WT and KO mice in the extent of histological findings such as increased
      cross-sectional areas of the neointima and the media, the number of proliferating
      smooth muscle cells, and the amount of collagen and fibronectin. Treatment with
      subpressor doses of Ang II after injury enhanced the growth of neointima in WT
      mice but not in KO mice. Moreover, treatment with the selective AT1 antagonist CV
      11974 before injury significantly decreased the formation of neointima in only WT
      mice, whereas treatment with the selective AT2 antagonist PD-123319 before injury
      had no effects in both animal groups. These results suggest that AT1-mediated Ang
      II signaling is not essential for the development of neointimal formation,
      although it may modify it.

PMID- 9933250
TI  - Nitric oxide/cAMP interactions in the control of rat renal vascular resistance.
AB  - This study aimed to characterize the interaction between nitric oxide (NO)- and
      cAMP-related pathways in the control of renal blood flow. Using the isolated
      perfused rat kidney model, we determined the effects of inhibition of NO
      formation by Nomega-nitro-L-arginine methyl ester (L-NAME; 1 mmol/L) and of NO
      administration by sodium nitroprusside (SNP, 10 micromol/L) on renal vascular
      resistance under conditions of elevated vascular cAMP levels. cAMP levels were
      increased either by adenylate cyclase activation via isoproterenol or by
      inhibition of cAMP phosphodiesterases (PDEs) 1, 3, and 4. We found that L-NAME
      markedly increased vascular resistance and that this effect was completely
      reversed by SNP. Both isoproterenol and inhibitors of the cAMP PDEs lowered basal
      vascular resistance. In the presence of isoproterenol (3 nmol/L) and inhibitors
      of PDE-1 [8-methoxymethyl-l-methyl-3-(2-methylpropyl)-xanthine; 8-MM-IBMX, 20
      micromol/L] and PDE-4 (rolipram, 20 micromol/L), L-NAME again substantially
      increased vascular resistance, and this effect of L-NAME was completely reversed
      by SNP. In the presence of the PDE-3 inhibitors milrinone (20 micromol/L) and
      trequinsin (200 nmol/L), however, both L-NAME and SNP failed to exert any
      additional effects. Because PDE-3 is a cGMP-inhibited cAMP PDE and because the
      vasodilatory effect of SNP was abrogated by the guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (20 micromol/L), our findings are
      compatible with the idea that an action of NO on PDE-3 could account for the
      vasodilatory properties of NO on the renal vasculature. Moreover, our findings
      suggest that PDE-3 activity is an important determinant of renal vascular
      resistance.

PMID- 9933251
TI  - Glucocorticoids downregulate cyclooxygenase-1 gene expression and prostacyclin
      synthesis in fetal pulmonary artery endothelium.
AB  - Prostacyclin (prostaglandin I2 [PGI2]) is a key mediator of pulmonary vascular
      function during early postnatal life, and its production in the pulmonary
      vasculature rises markedly during that period because of increasing expression of
      cyclooxygenase type 1 (COX-1). The postnatal rise in COX-1 may be due to the
      release of inhibition by glucocorticoids, since plasma glucocorticoid levels fall
      after birth and glucocorticoids decrease PGI2 synthesis in certain nonpulmonary
      cell types. We therefore studied the direct effects of dexamethasone (DEX) on COX
      1 expression in early-passage ovine fetal pulmonary-artery endothelial cells
      (PAECs). DEX (10(-10) to 10(-6) mol/L) caused a dose-related decrease in COX-1
      mRNA expression that was evident by 24 hours, was maximal at 10(-6) mol/L (50%
      inhibition), and was not due to changes in mRNA stability. There was a parallel
      decline in COX-1 protein expression. COX-1 protein rose following DEX withdrawal,
      and DEX blunted the stimulatory effect of 17beta-estradiol on COX-1 expression.
      DEX alone (10(-8) mol/L for 48 hours) caused a 93% fall in basal PGI2 production,
      and bradykinin- and A23187-stimulated PGI2 were diminished 96% and 94%,
      respectively. Similarly, PGI2 synthesis from arachidonic acid fell 86% with DEX;
      all of the above effects are consistent with COX-1 downregulation. The
      glucocorticoid receptor (GR) antagonist mifepristone (RU-486; 10(-6) mol/L)
      blocked the inhibitory effect of DEX, and GR expression was evident by immunoblot
      analysis. These findings indicate that glucocorticoids downregulate COX-1
      expression and PGI2 synthesis in fetal PAECs through the activation of PAEC GR
      and effects on COX-1 gene transcription. This mechanism may modulate pulmonary
      PGI2 production in the perinatal period, and it may also play a role in the
      effects of glucocorticoids on the systemic circulation at a variety of ages.

PMID- 9933252
TI  - Nitric oxide inhibits capacitative cation influx in human platelets by promoting
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase-dependent refilling of Ca2+
      stores.
AB  - Nitric oxide (NO) is a potent inhibitor of thrombin-induced increase in
      cytoplasmic free Ca2+ concentration and aggregation in platelets, but the precise
      mechanism of this inhibition is unclear. To measure Ca2+/Mn2+ influx in intact
      platelets and to monitor Ca2+ uptake into the stores in permeabilized platelets,
      fura-2 was used. In intact platelets, maximal capacitative Ca2+ and Mn2+ influx
      developed rapidly (within 30 s) after fast release of Ca2+ from the stores with
      thrombin (0.5 U/mL) or slowly (within 5 to 10 minutes) following passive Ca2+
      leak caused by inhibition of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase
      (SERCA) with 30 micromol/L 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ). NO (1
      micromol/L) inhibited capacitative Ca2+ and Mn2+ influx independently of the time
      after thrombin application. In contrast, the effect of NO on BHQ-induced Ca2+ and
      Mn2+ influx was observed only during the first few minutes after BHQ application
      and completely disappeared when capacitative cation influx reached its maximum.
      In Ca2+-free medium, NO reduced the peak Ca2+ rise caused by thrombin and
      significantly promoted Ca2+ back-sequestration into the stores. Both effects
      disappeared in the presence of BHQ. Inhibition of guanylate cyclase with H
      (1,2,4) oxadiazolo(4,3-a) quinoxallin-1-one (10 micromol/L) attenuated but did
      not prevent the effects of NO on cytoplasmic free Ca2+ concentration. Inhibition
      of Ca2+ uptake by mitochondria did not change the effects of NO. In permeabilized
      platelets, NO accelerated back-sequestration of Ca2+ into the stores after
      inositol-1,4,5-trisphosphate-induced Ca2+ release or after addition of Ca2+ (1
      micromol/L) in the absence of inositol-1,4,5-trisphosphate. The effect of NO
      depended on the initial rate of Ca2+ uptake and on the concentration of ATP and
      was abolished by BHQ, indicating the direct involvement of SERCA. These data
      strongly support the hypothesis that NO inhibits store-operated cation influx in
      human platelets indirectly via acceleration of SERCA-dependent refilling of Ca2+
      stores.

PMID- 9933253
TI  - Mechanism of nitric oxide-induced vasodilatation: refilling of intracellular
      stores by sarcoplasmic reticulum Ca2+ ATPase and inhibition of store-operated
      Ca2+ influx.
AB  - The precise mechanisms by which nitric oxide (NO) decreases free [Ca2+]i,
      inhibits Ca2+ influx, and relaxes vascular smooth muscle are poorly understood.
      In rabbit and mouse aorta, agonist-induced contractions and increases in [Ca2+]i
      were resistant to nifedipine, suggesting Ca2+ entry through non-L-type Ca2+
      channels. Relaxations to NO were inhibited by thapsigargin (TG) or cyclopiazonic
      acid (CPA) indicating the involvement of sarcoplasmic reticulum ATPase (SERCA).
      Studies of the effect of NO on [Ca2+]i and the rate of Mn2+ influx with fura-2
      fluorometry in rabbit aortic smooth muscle cells in primary culture were designed
      to test how SERCA is involved in mediating the response to NO. When cells were
      stimulated with angiotensin II (AII), NO accelerated the removal of Ca2+ from the
      cytoplasm, decreased [Ca2+]i, and inhibited Ca2+ and Mn2+ influx. Inhibition of
      SERCA abolished all the effects of NO. In contrast, inhibition of the
      Na+/Ca2+exchanger or the plasma membrane Ca2+ ATPase had no influence on the
      ability of NO to decrease [Ca2+]i. NO maximally decreased [Ca2+]i within 5 s,
      whereas significant inhibition of AII-induced Ca2+ and Mn2+ influx required more
      than 15 s. The inhibition of cation influx strictly depended on [Ca2+]o and
      functional SERCA, suggesting that during the delay before NO inhibits Ca2+
      influx, the influx of Ca2+ and the uptake into intracellular stores are required.
      In the absence of [Ca2+]o, NO diminished the AII-induced [Ca2+]i transient by a
      SERCA-dependent mechanism and increased the amount of Ca2+ in the stores
      subsequently released by ionomycin. The present study indicates that the initial
      rapid decrease in [Ca2+]i caused by NO in vascular smooth muscle is accounted for
      by the uptake of Ca2+ by SERCA into intracellular stores. It is proposed that the
      refilling of the stores inhibits store-operated Ca2+ influx through non-L-type
      Ca2+ conducting ion channels and that this maintains the decrease in [Ca2+]i and
      NO-induced relaxation.

PMID- 9933254
TI  - Potential role of a membrane-bound NADH oxidoreductase in nitric oxide release
      and arterial relaxation to nitroprusside.
AB  - The site of metabolism in vascular smooth muscle responsible for the release of
      nitric oxide (NO) from nitroprusside is not well established. In this study we
      observed that a membrane-bound NADH oxidoreductase in the pulmonary artery
      activates nitroprusside to release NO, and we examined whether this process could
      potentially participate in relaxation to nitroprusside. Relaxation to
      nitroprusside in bovine calf pulmonary artery is inhibited by a scavenger of NO
      and by an antagonist of NO stimulation of guanylate cyclase. A flavoprotein probe
      that inhibits pulmonary artery NADH oxidoreductase (1 micromol/L
      diphenyliodonium) and electron acceptors for NADH oxidoreductase (0.3 mmol/L
      nitroblue tetrazolium and 0.1 mmol/L ferricyanide) inhibited pulmonary artery
      relaxation to nitroprusside, but not to nitroglycerin. Pulmonary arteries were
      observed to promote the release of NO from nitroprusside in vitro, and NO release
      was inhibited by the presence of nitroblue tetrazolium, ferricyanide, and
      diphenyliodonium. In homogenates of pulmonary arteries, NADH (0.1 mmol/L)
      increased the release of NO from nitroprusside by approximately 6-fold, whereas
      NADPH, mitochondrial substrates, and other redox cofactors had minimal effects on
      NO release, and the action of NADH on nitroprusside was inhibited by nitroblue
      tetrazolium, ferricyanide, and diphenyliodonium. A membrane fraction enriched in
      NADH oxidoreductase activity showed a NADH-dependent release of NO from
      nitroprusside; nitroprusside caused NADH consumption, and it also inhibited the
      NADH-dependent reduction of nitroblue tetrazolium. Thus, a membrane-bound NADH
      oxidoreductase appears to contribute to the release of NO from nitroprusside, but
      not nitroglycerin, in calf pulmonary artery.

PMID- 9933255
TI  - Estrogen and tamoxifen metabolites protect smooth muscle cell membrane
      phospholipids against peroxidation and inhibit cell growth.
AB  - The goal of this study was to test the hypothesis that antioxidant estrogens, by
      a mechanism independent of the estrogen receptor, protect phospholipids residing
      in the plasma membrane of vascular smooth muscle cells from peroxidation and
      peroxidation-induced cell growth and migration. Peroxidation of membrane
      phospholipids was assessed by HPLC analysis of phospholipids extracted from rat
      aortic vascular smooth muscle cells prelabeled with cis-parinaric acid (a fatty
      acid that is susceptible to peroxidation, which quenches its fluorescent
      properties). Incubation of cells for 2 hours with the peroxyl radical donor 2,2'
      azobis-2,4-dimethylvaleronitrile (AMVN) caused peroxidation of all measured
      membrane phospholipids. This effect was attenuated by pretreating cells for 15
      minutes with 50 to 5000 ng/mL of 2-hydroxyestradiol (strong antioxidant but weak
      estrogen-receptor ligand) or 4-hydroxytamoxifen (strong antioxidant and potent
      estrogen-receptor ligand), but not by estrone or droloxifene (both weak
      antioxidants but potent estrogen-receptor ligands). Moreover, pretreatment of
      cells for 20 hours with physiological concentrations (0.3 ng/mL) of 2
      hydroxyestradiol or pharmacologically relevant concentrations of 4
      hydroxytamoxifen (40 ng/mL) also decreased AMVN-induced phospholipid
      peroxidation. Both 2-hydroxyestradiol and 4-hydroxytamoxifen were as effective as
      2,2,5, 7,8-pentamethyl-6-hydrochromane (an antioxidant homolog of vitamin E) in
      attenuating AMVN-induced peroxidation of membrane phospholipids. Also,
      physiological concentrations of 2-hydroxyestradiol, but not estrone, and
      pharmacologically relevant concentrations of 4-hydroxytamoxifen attenuated AMVM
      induced DNA synthesis, cell proliferation, and cell migration. These studies
      demonstrate in vascular smooth muscle cells that antioxidant estrogens via a non
      estrogen receptor-dependent mechanism attenuate peroxidation of membrane
      phospholipids and peroxidation-induced cell growth and migration.

PMID- 9933258
TI  - Osteopontin. Between a rock and a hard plaque.

PMID- 9933256
TI  - Distinct renin isoforms generated by tissue-specific transcription initiation and
      alternative splicing.
AB  - The aspartyl protease renin catalyzes the initial and rate-limiting step in the
      formation of the biologically active peptide angiotensin II. It is mainly
      synthesized in the kidney as a preprohormone and secreted via constitutive and
      regulated pathways. We identified a novel transcript of the rat renin gene, renin
      b, characterized by the presence of an alternative first exon (exon 1b) that is
      spliced to exon 2 of the known transcript, termed renin a. We demonstrated that
      renin b is exclusively expressed in the brain. In contrast, renin a was not
      expressed in the brain. Using primer extension assays, we mapped the
      transcriptional start site of this novel mRNA within intron 1 of the rat genomic
      sequence, suggesting the presence of a brain-specific promoter within intron 1.
      The presence of a brain-specific renin isoform is evolutionally conserved, as
      demonstrated by the finding of renin b isoforms in mice and humans. The predicted
      protein renin b lacks the prefragment as well as a significant portion of the
      profragment and is therefore predicted not to be a secreted protein, unlike the
      classically described isoform renin a. As shown by in vitro translation of full
      length renin b mRNA in the presence of microsomal membranes, renin b was not
      targeted into the endoplasmatic reticulum and remained intracellularly in
      transiently transfected AtT-20 cells. These findings provide evidence for a novel
      pathway of intracellular angiotensin generation that occurs exclusively in the
      brain.

PMID- 9933257
TI  - Molecular genetics of congenital heart disease. A problem of faulty septation.

PMID- 9933259
TI  - The american stroke association : A division of the american heart association 

PMID- 9933260
TI  - Importance of intracranial atherosclerotic disease in patients with symptomatic
      stenosis of the internal carotid artery. The North American Symptomatic Carotid
      Endarterectomy Trail.
AB  - BACKGROUND AND PURPOSE: The estimated prevalence of intracranial atherosclerotic
      disease (IAD) in patients with stenosis of the extracranial internal carotid
      artery (ICA) varies between 20% and 50%. The benefits of carotid endarterectomy
      (CE) in patients with both IAD and symptomatic extracranial ICA stenosis are
      uncertain. METHODS: The association between IAD and other vascular risk factors
      and with the risk of stroke at 3 years were studied in patients with symptomatic
      extracranial ICA stenosis who participated in the North American Symptomatic
      Carotid Endarterectomy Trial (NASCET). Since the NASCET protocol excluded severe
      IAD, only a modest number of patients in this category could be studied. RESULTS:
      IAD was observed in one third of the patients. In medically treated patients, the
      relative risk of stroke associated with IAD varied from 1.3 (95% CI, 0.9 to 1.9)
      with extracranial ICA stenosis of <50% to 1.8 (95% CI, 1.1 to 3.2) with 85% to
      99% ICA stenosis. In contrast, IAD did not affect the risk of stroke among
      surgically treated patients. To prevent 1 stroke ipsilateral to the symptomatic
      ICA stenosis over 3 years in patients who have also IAD, 12 patients with 50% to
      69%, 5 patients with 70% to 84%, and 3 patients with 85% to 99% ICA stenosis have
      to undergo CE. In patients without IAD these numbers are 26, 7, and 6,
      respectively. CONCLUSIONS: IAD is an independent risk factor for subsequent
      stroke in medically treated patients with symptomatic ICA stenosis. CE reduces
      this risk. The additional risk imposed by IAD in medically treated patients
      enhances the value of CE in patients with moderate symptomatic extracranial ICA
      stenosis. Detection of IAD, requiring angiography, is an important prelude to
      planning CE in symptomatic patients with moderate extracranial ICA stenosis.

PMID- 9933261
TI  - Early clinical and radiological predictors of fatal brain swelling in ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Early identification of acute stroke patients at risk of
      fatal brain swelling is necessary to facilitate implementation of aggressive
      therapies. Initial clinical, laboratory, and CT characteristics that may be used
      as selection criteria were analyzed to determine predictors of herniation and
      neurological death. METHODS: Data from the placebo arm of the Lubeluzole
      International-9 trial were reviewed to identify patients with fatal brain edema.
      Early clinical, laboratory, and radiographic parameters were evaluated in a case
      control design. Initial CT scans were analyzed for early ischemic abnormalities
      by 2 blinded investigators. RESULTS: Twenty-three patients died from brain
      swelling, with minimum baseline National Institutes of Health Stroke Scale
      (NIHSS) scores of 20 (n=12; mean, 23.2+/-1.8) with left and 15 (n=11; mean,
      17.6+/-2.2) with right hemispheric infarctions (P=0. 0001). A sample of 112
      subjects with comparably severe strokes, but who did not die from brain swelling,
      was selected from the remaining population according to the same NIHSS scores.
      Among clinical and laboratory characteristics, nausea/vomiting within 24 hours
      after onset (odds ratio [OR], 5.1; 95% CI, 1.7 to 15.3; P=0.003) and 12-hour
      systolic blood pressure >/=180 mm Hg (OR, 4.2; 95% CI, 1.4 to 12.9; P=0.01) were
      independently associated with fatal brain swelling. Among radiographic factors,
      only hypodensity of >50% of the middle cerebral artery territory on initial CT
      scan was an independent predictor (OR, 6.1; 95% CI, 2.3 to 16.6; P=0.0004).
      CONCLUSIONS: Patients with baseline NIHSS score >/=20 with left or >/=15 with
      right hemispheric infarctions within 6 hours of symptom onset who also have
      nausea/vomiting or >50% middle cerebral artery territory hypodensity are at high
      risk for developing fatal brain swelling.

PMID- 9933262
TI  - Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke
      clinical trials. The RANTTAS Investigators.
AB  - BACKGROUND AND PURPOSE: Reduction in infarct volume is the standard measure of
      therapeutic success in animal stroke models. Reduction in infarct volume has been
      advocated as a biological surrogate or auxiliary outcome measure for human stroke
      clinical trials to replace or supplement deficit, disability, and global clinical
      scales. However, few studies have investigated correlations between infarct
      volume and clinical end points in acute ischemic stroke patients. METHODS: CT
      scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients
      enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute
      Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any
      vessel distribution. Infarct volume was measured by operator-assisted
      computerized planimetry. RESULTS: One hundred thirty-two patients had visible new
      supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile
      range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct.
      Correlations with standard 3-month outcome scales and mortality were as follows:
      Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of
      Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone,
      correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality,
      r=0.32. CONCLUSIONS: Subacute CT infarct volume correlates moderately with 3
      month clinical outcome as assessed by widely used neurological and functional
      assessment scales. The modesty of this linkage constrains the use of infarct
      volume as a surrogate end point in ischemic stroke clinical trials.

PMID- 9933264
TI  - Concentration changes of malondialdehyde across the cerebral vascular bed and
      shedding of L-selectin during carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Oxidative stress has been postulated to account for
      delayed neuronal death due to ischemia/reperfusion. We investigated cerebral
      formation of malondialdehyde as an index of lipid peroxidation in relation to
      different sources of reactive oxygen species in patients undergoing carotid
      endarterectomy. METHODS: In 25 patients undergoing carotid endarterectomy,
      jugular venous-arterial concentration differences of brain metabolites,
      malondialdehyde, plasma total antioxidant status, and soluble P-selectin and L
      selectin were measured. A carotid artery shunt (n=5) was placed only after
      complete loss of somatosensory evoked potentials, indicating a focal cerebral
      blood flow <15 mL/min per 100 g. RESULTS: As an indication of cerebral lipid
      peroxidation, jugular venous-arterial malondialdehyde concentration differences
      were significantly enhanced before reperfusion, and an additional rise was
      observed 15 minutes after reperfusion. Plasma total antioxidant status
      significantly decreased during carotid artery occlusion only in patients with
      carotid artery shunt. This decrease was matched by cerebral formation of
      adenosine, hypoxanthine, and nitrite/nitrate. While jugular venous-arterial
      concentration differences of soluble P-selectin showed changes similar to those
      of malondialdehyde, the concentration difference for soluble L-selectin was
      enhanced exclusively at 15 minutes after reperfusion. CONCLUSIONS: Short-term
      incomplete cerebral ischemia/reperfusion significantly enhanced cerebral lipid
      peroxidation, as indicated by malondialdehyde formation. The generation of
      reactive oxygen species by xanthine oxidase or nitric oxide metabolism might be
      involved in the induction of lipid peroxidation. The additional rise in cerebral
      release of malondialdehyde was found to coincide with a significant activation of
      polymorphonuclear leukocytes across the cerebral circulation.

PMID- 9933263
TI  - Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with
      future risk of stroke and cardiovascular disease: a prospective study in middle
      aged to elderly men with treated hypertension.
AB  - BACKGROUND AND PURPOSE: Several cross-sectional and prospective studies have
      indicated that high titers of antibodies to Chlamydia pneumoniae and
      cytomegalovirus (CMV) are associated with coronary heart disease. The aim of the
      present study was to examine whether elevated titers of antibodies to these
      pathogens are predictive of not only coronary but also cerebrovascular disease.
      METHODS: Serum titers of antibodies to C pneumoniae (IgM, IgG, IgA, IgG immune
      complex) and CMV (IgG) were determined at baseline (n=130) and after 3.5 years
      (n=111) in a total sample of 152 men. All individuals had treated hypertension
      and at least 1 additional risk factor for cardiovascular disease
      (hypercholesterolemia, smoking, or diabetes mellitus) and constituted 93% of a
      randomly selected subgroup (n=164) of patients participating in a multiple risk
      factor intervention study. RESULTS: Elevations of any or both of the IgA or IgG
      titers to C pneumoniae at entry or after 3.5 years were found in 84 cases (55%).
      Of those with high titers at entry, 97% remained high at the 3.5 year
      reexamination. After 6.5 years of follow-up, high titers to C pneumoniae at entry
      were associated with an increased risk for future stroke (relative risk [RR],
      8.58; P=0.043; 95% CI, 1.07 to 68.82) and for any cardiovascular event (RR, 2.69;
      P=0.042; 95% CI, 1.04 to 6.97). A high serum titer of antibodies to CMV was found
      in 125 cases (85%), and this was not associated with an increased risk of future
      cardiovascular events. CONCLUSIONS: Seropositivity for C pneumoniae, but not for
      CMV, was associated with an increased risk for future cardiovascular disease and,
      in particular, stroke.

PMID- 9933265
TI  - Should we screen for familial intracranial aneurysm?
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to establish whether
      individuals with a family history of >/=2 first-degree relatives with
      intracranial aneurysm should be offered screening for aneurysm. METHODS: We
      derived 3 theoretical models and calculated the outcomes of screening with
      magnetic resonance angiography (MRA) followed by digital subtraction angiography
      (DSA) if MRA was positive (model 1), screening with DSA alone (model 2), and not
      screening (model 3). Screening was repeated at intervals of 10 years, and
      aneurysms detected were treated surgically. We assumed a prevalence of aneurysm
      of 9.8% (95% CI, 8.9% to 10.6%) in the population screened, an annual rupture
      rate of asymptomatic aneurysm of 0.8% (95% CI, 0.4% to 1.5%), and a 75% chance of
      poor outcome from rupture. We assumed the sensitivity and specificity of MRA were
      each 90% and the risk of DSA was 0.1%. The risk of surgery was taken as 5.1%.
      RESULTS: Screening 1000 individuals on 3 occasions with MRA and DSA or with DSA
      alone followed by surgery resulted in poor outcome in 14 and 18 individuals,
      respectively, over 30 years. Without screening, poor outcome occurred in 15
      individuals over the same period of time. CONCLUSIONS: Screening is not an
      effective way of reducing morbidity and mortality from ruptured intracranial
      aneurysm in individuals with a history of >/=2 affected first-degree relatives
      with ruptured intracranial aneurysm unless the expected incidence of asymptomatic
      aneurysm is considerably >10%.

PMID- 9933266
TI  - Risk of cerebral angiography in patients with subarachnoid hemorrhage, cerebral
      aneurysm, and arteriovenous malformation: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: A well-defined complication rate of cerebral angiography
      in patients with subarachnoid hemorrhage (SAH), cerebral aneurysm, and
      arteriovenous malformation (AVM) would be useful to physicians making decisions
      regarding the imaging of these patients. We sought to define a statistically
      significant complication rate through meta-analysis of prospective studies in the
      literature. METHODS: Meta-analysis of 3 published prospective studies of
      complications in cerebral angiography was performed to specifically define the
      risk of cerebral angiography in patients presenting with SAH, cerebral aneurysm,
      and AVM. The complication rates for cerebral angiography in patients with SAH and
      AVM/aneurysm without SAH were compared with the complication rates in patients
      who underwent cerebral angiography for transient ischemic attack (TIA)/ischemic
      stroke with use of the Fisher exact test. RESULTS: The combined risk of permanent
      and transient neurological complication was significantly lower in patients with
      SAH compared with patients with TIA/stroke (1.8% versus 3.7%; P=0.03). The
      combined risk of permanent and transient neurological complication was
      significantly lower in patients with aneurysm/AVM without SAH compared with
      patients with TIA/stroke (0.3% versus 3.7%; P=0.001). When the patients with SAH
      and cerebral aneurysm/AVM were combined, the overall risk of permanent and
      transient neurological complication was significantly lower than for the
      TIA/stroke patients (0.8% versus 3.0%; P=0.001), as was the risk of permanent
      neurological complication (0.07% versus 0.7%; P=0.004). CONCLUSIONS: The risk of
      permanent neurological complication associated with cerebral angiography in
      patients with SAH, cerebral aneurysm, and AVM is quite low (0.07%). This risk is
      lower than previously recognized.

PMID- 9933268
TI  - Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based
      cohort.
AB  - BACKGROUND AND PURPOSE: Leptin, important for body weight regulation, may be
      involved in the pathogenesis of the insulin resistance syndrome, associated with
      cardiovascular disease. We tested to determine whether leptin is a risk marker
      for first-ever stroke in a nested case-referent study. METHODS: We identified 113
      patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke)
      who, before the stroke, had participated in population-based health surveys in
      northern Sweden. Referents were matched for sex, age, date and type of health
      survey, and geographic region. Blood pressure (BP), body mass index (BMI), and
      presence of smoking, diabetes, and hypertension were recorded. Total cholesterol,
      insulin, and leptin were analyzed in stored samples. Risk markers for first-ever
      stroke were analyzed by conditional logistic regression analysis. RESULTS:
      Patients with hemorrhagic stroke had higher levels of BMI and systolic and
      diastolic BPs. Leptin levels were 72% and 59% higher in males and females,
      respectively, with hemorrhagic stroke versus referents. Patients with ischemic
      stroke more often had hypertension, diabetes mellitus, and higher fasting glucose
      and insulin levels. A diagnosis of hypertension and elevated systolic and
      diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in
      univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels
      together with hypertension (OR=16.28; 95% CI, 1.49 to 177.3) remained as
      significant risk markers in a multivariate model. The combination of high leptin
      and high systolic or diastolic BP were associated with a profoundly increased
      risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes,
      hypertension, and obesity (BMI >/=27), together with high levels of insulin,
      glucose, systolic and diastolic BP, were significant risk markers for first-ever
      ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to
      3.86) remained as an independent risk marker in a multivariate model.
      CONCLUSIONS: Plasma leptin is strongly associated with an increased risk for
      first-ever hemorrhagic stroke, independent of other risk markers for
      cardiovascular disease. Leptin may be an important link in the development of
      cardiovascular disease in obesity.

PMID- 9933267
TI  - Intrathecal expression of proteins regulating apoptosis in acute stroke.
AB  - BACKGROUND AND PURPOSE: The neuronal death that accompanies an ischemic stroke
      has previously been attributed to a necrotic process. However, numerous studies
      in experimental models of ischemia have recently indicated that programmed cell
      death, also called apoptosis, may contribute to neuronal death. The aim of the
      present study was to investigate the intrathecal levels of proteins regulating
      apoptosis in acute stroke and to relate these levels to brain damage and to
      production of proinflammatory and anti-inflammatory cytokines. METHODS: Thirty
      stroke patients were studied prospectively on days 0 to 4, 7 to 9, 21 to 26, and
      after day 90 with clinical evaluation, radiological assessment, and analysis of
      cerebrospinal fluid (CSF) levels of soluble (s) Fas/APO-1 and sbcl-2, 2 proteins
      that regulate apoptosis. In addition, analysis of the intrathecal levels of
      cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, granulocyte-macrophage
      colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha was
      performed. Nineteen CSF samples from healthy subjects were used for control
      purposes. The patients were examined with MRI 1 to 3 months after stroke onset
      for measurement of infarct volume RESULTS: Significantly decreased CSF levels of
      sFas/APO-1 were observed during the entire observation period, with a maximal
      decrease on day 21 after the onset of stroke. The intrathecal levels of sFas/APO
      1 were significantly negatively correlated with the volume of brain infarct and
      with the neurological deficit 3 weeks and 3 months after the onset of the stroke.
      In addition, the intrathecal levels of sFas/APO-1 were significantly correlated
      with the levels of IL-1beta, IL-6, IL-10, and GM-CSF 3 weeks after the onset of
      the disease. The intrathecal levels of sbcl-2 were significantly decreased during
      the first 3 days after stroke onset and at the same time were positively
      correlated with the levels of IL-6 and tumor necrosis factor-alpha. CONCLUSIONS:
      Our study demonstrates decreased intrathecal levels of proteins with
      antiapoptotic properties, suggesting that patients with acute stroke display a
      propensity toward apoptosis. Control of factors regulating apoptosis may lead to
      decreased delayed brain damage in stroke.

PMID- 9933269
TI  - Epidemiology of recurrent cerebral infarction: a medicare claims-based comparison
      of first and recurrent strokes on 2-year survival and cost.
AB  - BACKGROUND AND PURPOSE: Because recurrent strokes will tend to leave patients
      with greater disability than first strokes, patients with recurrent strokes
      should have poorer outcomes on average than those with first strokes. The extent
      of this difference has, however, not yet been estimated with precision. METHODS:
      Using a random 20% sample of Medicare patients aged 65 years and older admitted
      with a primary diagnosis of cerebral infarction during calendar year 1991, we
      used historical data from the previous 4 years to classify patients as having
      either first or recurrent stroke and followed survival and direct medical costs
      for 24 months after stroke. First and recurrent stroke groups were compared with
      the log-rank test (survival) and t test (cost) and also multivariate modeling.
      RESULTS: Survival from first stroke is consistently better than that for
      recurrent stroke: 24-month survival was 56.7% versus 48.3%, respectively. Costs
      were similar for the initial hospital stay and in months 1 to 3 after stroke.
      During months 4 to 24 after stroke, total costs were higher among those with
      recurrent stroke by approximately $375/mo across all patients, with this
      difference being greatest for younger patients and least for patients aged 80
      years or older. Most of the difference in total monthly cost was attributable to
      nursing home utilization (averaging approximately $150/mo) and acute
      hospitalization (averaging approximately $120/mo). CONCLUSIONS: Patients with
      recurrent stroke have, on average, poorer outcomes than those with first stroke.
      To be as accurate as possible, clinical policy analyses should use different
      estimates of health and cost outcomes for first and recurrent stroke.

PMID- 9933270
TI  - Variations in case fatality and dependency from stroke in western and central
      Europe. The European BIOMED Study of Stroke Care Group.
AB  - BACKGROUND AND PURPOSE: There are significant variations in mortality rates from
      stroke in Europe. A European Union BIOMED Concerted Action was established to
      assess and determine the reasons for the variations in case fatality and
      disability after stroke. METHODS: Hospital-based stroke registers were
      established in 12 centers in 7 western and central European countries to collect
      demographic, clinical, and resource use details at the time of first-ever stroke
      during 1993-1994. At 3 months, details of survival, activity of daily living
      score, and use of health services were recorded. Multinomial logistic regression
      was used to estimate the relationship between centers and outcome (dead,
      functionally independent, functionally dependent), with adjustment for case mix
      and resource use variables, and to predict outcomes for the full cohort. This
      should minimize the bias due to loss to follow-up. RESULTS: A total of 4534
      stroke events were registered. The mean age was 71.9 years (SD, 12.53). There
      were significant differences between centers for all case mix and resource use
      variables (P<0. 001). Multinomial logistic regression modeling of outcome
      indicated that for those patients initially unconscious (588), center was not
      significantly related to outcome (P=0.427). For those initially conscious, there
      were wide variations in death and dependency between centers after adjustment for
      case mix, type of bed, and use of CT scan. The predicted proportion dead at 3
      months ranged from 42% (95% CI, 35% to 49%) in one UK center to 19% (95% CI, 14%
      to 24%) in France. CONCLUSIONS: Areas with high mortality rates within western
      and central Europe have been identified for stroke outcome, and there appears to
      be opportunity for considerable health gain in certain centers. Adjustment for
      case mix and health service resource use does not explain these differences in
      outcome. Although there are true differences in outcome, the aspects of care that
      need to be altered to improve outcome remain unclear despite detailed data
      collection. Comparisons of outcome of the same design used in the present study
      do not allow rational policy decisions to be made.

PMID- 9933271
TI  - Socioeconomic differences in stroke among Dutch elderly women: the Rotterdam
      Study.
AB  - BACKGROUND AND PURPOSE: We sought to assess the association between socioeconomic
      status and the risk of stroke among elderly women. Methods--The association
      between socioeconomic status and stroke emerged in cross-sectional and
      longitudinal data on 4274 female participants of the Rotterdam Study, a
      prospective, population-based, follow-up study in the Netherlands among older
      subjects. RESULTS: A history of stroke was more common among women in lower
      socioeconomic strata. The same trend was observed for the relationship between
      the lowest socioeconomic groups and the incidence of stroke. Risk factors for
      stroke were not related to socioeconomic status in a consistent manner. Smoking,
      history of cardiovascular diseases, and overweight were more common in lower
      socioeconomic groups. However, socioeconomic differences in hypertension,
      antihypertensive drug use, prevalence of atrial fibrillation, and prevalence of
      left ventricular hypertrophy were not observed. The complex of established risk
      factors could only partly explain the association between socioeconomic status
      and stroke. CONCLUSIONS: There is a strong association among elderly women
      between socioeconomic status and stroke. The association could only partly be
      explained by known risk factors. Our findings indicate that not only the actual
      risk profile but also risk factors earlier in life may be of importance.

PMID- 9933272
TI  - Stroke incidence and case fatality in southern Greece: the Arcadia stroke
      registry.
AB  - BACKGROUND AND PURPOSE: For Greece, information on incidence of stroke and
      distribution of type of stroke has not been reported. We determined the incidence
      of first-ever stroke in men and women, the incidence of stroke by type, and the
      associated case fatality. METHODS: A population-based registry was established in
      the Arcadia province, located in eastern central Peloponessos, in the southern
      part of Greece. Between November 1, 1993, and October 31, 1995, all subjects with
      a first-ever stroke were identified. For case ascertainment, information from
      death certificates, hospital records, public health centers, and general
      practitioners was used. RESULTS: During a 24-month period, 555 subjects with a
      first-ever stroke were registered. The incidence rates (per 100 000) by age group
      (18 to 34, 35 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, >/=85 years) for men
      were 5, 31, 113, 240, 662, 1275, and 3218, respectively. For women, the rates
      were 11, 18, 48, 196, 478, 1166, and 2137, respectively. Age- and sex
      standardized to the European population, the annual incidence rate for subjects
      aged 45 to 84 years was 319.4/100 000 (95% CI, 283 to 356). In men, cerebral
      infarction was diagnosed in 81% of cases, intracerebral hemorrhage in 16%, and
      subarachnoid hemorrhage in 2%. For women, these figures were 85%, 12%, and 3%,
      respectively. The 28-day case fatality rate was 26.6% (95% CI, 22.9% to 30.2%),
      with no differences between men and women. Case-fatality increased with age and
      was higher for intracerebral hemorrhage than for cerebral infarction.
      CONCLUSIONS: The incidence of stroke in our population-based study ranks low part
      compared with other European studies. The distribution of stroke types and case
      fatality rate appear to be similar to those of other industrialized countries.

PMID- 9933273
TI  - Incidence trends of ischemic stroke and transient ischemic attacks in a well
      defined French population from 1985 through 1994.
AB  - BACKGROUND AND PURPOSE: The changing incidence of ischemic stroke is of major
      concern in view of its public health impact, to define the population concerned,
      to identify risk factors, and to set up health-care systems. The aim of this
      study was to evaluate the time trends associated with the incidence of all the
      subtypes of ischemic stroke and transient ischemic attacks in a well-defined
      population for 10 years. METHODS: Since 1985, a population registry has recorded
      each patient living in Dijon (France) who suffered from a cerebrovascular disease
      (CVD) regardless of the type of management. This study involved all patients
      suffering from their first ischemic stroke and their first transient ischemic
      attacks (TIAs) during 1 calendar year between January 1, 1985 and December 31,
      1994. The incidence changes according to age, sex, and type of cerebral ischemic
      event (cortico-subcortical infarct, lacunar infarct, and TIA) were studied on the
      basis of their annual variations. RESULTS: During the 10-year study period, 834
      cortico-subcortical infarcts (52.1%), 296 lacunar infarcts (18.5%), 369 TIAs
      (23.1%), and 101 undetermined ischemic strokes (6.3%) were collected. The
      incidence of all ischemic events was relatively stable in both sexes over the 10
      year period. However, the incidence rates differed according to age and type of
      ischemia. An increased incidence of cerebral cortico-subcortical infarct was
      observed in patients older than 75 years of age (+5.45% annual change [AC] in
      men, P<0.05; +5. 09% AC in women, NS). In parallel, a higher proportion of
      emboligenic cardiac arrhythmias was observed in these patients (P<0. 001). The
      incidence of lacunar infarcts tended to decrease, regardless of age but mainly in
      men under younger than 75 years of age (-12.74% AC in men, NS; +0.31% AC in
      women, NS). The incidence of TIAs was relatively stable in both sexes. Because
      our population consisted of a large number of elderly subjects, the increase in
      cardioembolic causes could partially explain the increased incidence of cerebral
      cortico-subcortical infarcts in patients older than 75 years of age. CONCLUSIONS:
      These preliminary data emphasize the importance of stroke surveillance in
      considering the variations of the different mechanisms of ischemic
      cerebrovascular disease. Although the incidence of TIA is stable and the
      incidence of lacunes tends to decrease in men, mainly before 75 years of age, we
      emphasize the rise of the crude incidence of cortico-subcortical infarcts in men
      older than 75 years of age, induced by an increase in cardioembolic causes.

PMID- 9933274
TI  - Risk factors for silent cerebral infarcts in subcortical white matter and basal
      ganglia.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to clarify whether the
      relevant risk factors for silent cerebral infarcts (SCIs) in subcortical white
      matter (WM) are different from those in the basal ganglia (BG). METHODS: Subjects
      of this study were 219 adults without a history of stroke or transient ischemic
      attack and without any abnormality on a neurological examination who
      consecutively visited the neurology service in our hospital between January 1994
      and November 1997 requesting medical evaluation for possible cerebrovascular
      diseases. Subjects included 141 men and 78 women ranging in age from 33 to 83
      years (mean+/-SD, 63.2+/-9.5 years). We performed brain MRIs and cervical/cranial
      MR angiographies on all subjects. In this study, SCI was defined as a focal
      lesion >5 mm in diameter that was prolonged on both T2-weighted and proton
      density images. RESULTS: SCIs in the WM and/or BG were detected in 88 (40.2%) of
      the 219 subjects. No SCI >15 mm was observed in this series. Fifty of the
      subjects had SCIs only in the WM, 32 subjects had SCIs in both the WM and BG, and
      6 subjects had SCIs only in the BG. Thus, 82 (93.2%) of 88 subjects with SCIs had
      lesions in the WM. Most subjects with SCIs in the BG also had SCIs in the WM.
      Multiple logistic regression analyses revealed that age, female sex, and
      hypertension were significant and independent predictors of SCIs in the WM, and
      that age, a history of ischemic heart disease, and carotid artery stenosis were
      significant and independent predictors of SCIs in the BG. CONCLUSIONS: The
      present study indicated that the relevant risk factors for SCIs in the WM and
      those for SCI in the BG were different. Our results suggest that SCIs are prone
      to first appear in the WM in association with aging and hypertension, and the
      additional appearance of SCIs in the BG predicts a progression of generalized
      atherosclerosis that is manifested in the carotid and coronary arteries.

PMID- 9933275
TI  - Prevalence and associations of MRI-demonstrated brain infarcts in elderly
      subjects with a history of transient ischemic attack. The Cardiovascular Health
      Study.
AB  - BACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of
      brain abnormalities seen on MR images obtained in older subjects with transient
      ischemic attack (TIA) is not clear. We studied the prevalence and risk factors
      associated with MRI-demonstrated infarcts in elderly subjects with a history of
      TIA. METHODS: Participants of the Cardiovascular Health Study, aged 65 years or
      more and without prior stroke, were studied with brain MRI (n=3456). The
      prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and
      without TIA. The cardiovascular risk factors and clinical and subclinical
      cardiovascular disease associated with MRI infarcts were studied in subjects with
      TIA. RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts
      than subjects without TIA (46% versus 28%; P<0.001). The unadjusted odds ratio
      for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and
      remained significantly elevated after adjustments for risk factors and
      cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects
      with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima
      media thickness (P=0.01) were the only factors predictive of the presence of MRI
      infarcts by stepwise logistic regression analysis. CONCLUSIONS: MRI infarcts are
      imaging manifestations of clinically important cerebrovascular disease in
      subjects with a history of TIA, given their increased prevalence and positive
      association with increased diastolic blood pressure and internal carotid artery
      intima-media thickness.

PMID- 9933278
TI  - CO2 reactivity testing without blood pressure monitoring?
AB  - BACKGROUND AND PURPOSE: Responsiveness to CO2 is an established test of
      cerebrovascular reserve capacity. Arterial partial pressure of CO2 (PCO2) and
      arterial blood pressure (BP) are key parameters for cerebral blood flow. To
      investigate the interaction between PCO2 and BP, we performed a study with
      simultaneous measurement of CO2 and BP during CO2 reactivity testing with
      transcranial Doppler sonography. METHODS: Eighty-one healthy volunteers, aged 19
      to 74 years, underwent examination defined by a protocol with multimodality
      monitoring of BP, heart rate (HR), PCO2, and Doppler frequencies (DFs) of the
      left middle cerebral artery (MCA). Reproducibility was tested in a subgroup of 14
      volunteers >/=65 years of age by CO2 reactivity testing on different days.
      RESULTS: Increase of PCO2 was accompanied by a parallel increase of mean+/-SD
      time values of DF (3. 6+/-1.6%/mm Hg CO2). BP levels were significantly elevated
      after 60-second hypercapnia (mean values, 0.5+/-0.55 mm Hg/mm Hg CO2). A
      significant decrease over time was seen only for pulsatility in DF but not in BP.
      Analysis of variance and covariance with repeated measures revealed a highly
      significant effect of CO2 on MCA Doppler shift. A less-pronounced effect on DF
      was seen for BP. Correlation analysis showed no significance for CO2 reactivity,
      but a significant correlation between test and retest was seen in BP-related CO2
      reactivity. CONCLUSIONS: The CO2 response curve showed the known linear increase
      of DF. The parallel significant increase in BP most likely results from
      activation of the central sympathetic nervous system. The poor reproducibility
      for Doppler CO2 reactivity is to some extent explainable by variability of BP.
      CO2-induced increases in BP can have relevant influence on MCA Doppler shift and
      lead to misinterpretation of Doppler CO2 test results.

PMID- 9933277
TI  - Characterization of white matter damage in ischemic leukoaraiosis with diffusion
      tensor MRI.
AB  - BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying
      ischemic leukoaraiosis is only available postmortem, and there are limited data
      on histological appearances early in the disease. Diffusion tensor imaging allows
      determination of the directionality of diffusion, which is greater in the
      direction of white matter bundles. Therefore, the technique might be expected to
      show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine
      patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical
      lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor
      imaging was performed, and maps of diffusion trace and fractional anisotropy were
      constructed. Mean values of trace and fractional anisotropy were determined in
      standard regions of the anterior and posterior white matter in both hemispheres.
      RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal
      pattern was found, with loss of anisotropy and increased trace in the white
      matter. For example, in the right anterior white matter mean (SD) trace/3 was
      1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In
      the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78
      (0.09) in controls (P<0.001). Within the white matter regions, there was a strong
      negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001).
      CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this
      patient group is consistent with axonal loss and gliosis leading to impairment to
      and loss of directional diffusion. The "in vivo histological" information
      obtained may be useful in monitoring disease progression and in investigating the
      pathogenesis of the cognitive impairment that may be present.

PMID- 9933276
TI  - Evaluation of early computed tomographic findings in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Detection of large, hypoattenuated brain-tissue volume on
      hyperacute CT scan has been suggested as an exclusion criterion for early
      intravenous tissue plasminogen activator (IV-tPA) treatment. This study assessed
      the reliability of detection for these findings and their relationship to
      outcome. METHODS: Fifty hyperacute CT scans (<6 hours after ictus) were selected
      from a randomized trial evaluating IV-tPA (ATLANTIS trial). Three
      neuroradiologists blinded to all clinical information evaluated scans for degree
      of MCA territory involvement (<33% or >33%) and the presence of a hyperdense MCA.
      Evaluations were compared with 24-hour scan results, 30-day infarct volumes, and
      baseline NIH stroke scale scores (NIHSS). RESULTS: Readers reliably evaluated the
      degree of MCA territory hypodensity (intraclass correlation=0.53, P<0.001), with
      all 3 readers agreeing in 36 of 50 cases (72%). They correctly called >33%
      involvement with a sensitivity of 60% to 85% and a specificity of 86% to 97%. The
      baseline NIHSS was higher when >33% MCA hypodensity was seen (P=0. 021).
      Detection of significant hypodensity (>33%) correlated with poorer outcome. When
      >33% hypodensity was not detected, mean 30-day infarct volumes were 27.0 to 33.0
      cm3, versus 84.3 to 123.1 cm3 when >33% hypodensity was present (P=0.002).
      CONCLUSIONS: Detection of MCA territory hypodensity on hyperacute CT scans is a
      sensitive, prognostic, and reliable indicator of the amount of MCA territory
      undergoing infarction.

PMID- 9933279
TI  - Standardization of carotid ultrasound: a hemodynamic method to normalize for
      interindividual and interequipment variability.
AB  - BACKGROUND AND PURPOSE: Accurate carotid Doppler examination is an important
      issue in the light of large endarterectomy trials, but recommended cutoff values
      for detection of >70% stenosis vary widely. Standardization of diagnostic
      criteria should consider patient variation and instrument variability. METHODS:
      We prospectively analyzed various Doppler parameters in 44 patients undergoing
      carotid angiography to evaluate whether normalization through individual
      reference measurements from the common carotid artery or the distal internal
      carotid artery could improve accuracy. For assessment of interindividual and
      interequipment variability, we performed repeated measurements of 40 carotid
      arteries in 21 patients. Two color-coded duplex ultrasound systems were compared
      for machine variability estimation: Hewlett Packard SONOS 2500 and ATL Ultramark
      9 HDI. RESULTS: Intrastenotic divided by distally recorded mean blood flow
      velocity (mean velocity ratio) showed the closest correlation with angiography:
      R2=0.93. Mean velocity ratio >5 was 97% sensitive and 98% specific for detection
      of >70% carotid stenosis. Intrastenotic blood flow velocities were significantly
      different between the 2 duplex systems (0.22+/-0.16 versus 0.17+/-0. 11 m/s;
      P<0.001), whereas mean velocity ratio values did not differ significantly.
      Interobserver variation expressed as 95% CI for predicted stenosis between 2
      observers was 13.6% (peak systolic velocity) and 15.4% (mean velocity ratio).
      CONCLUSIONS: A mean velocity ratio using distal reference measurement in the
      internal carotid artery can normalize for interindividual and interequipment
      variability.

PMID- 9933280
TI  - An additional monitoring of regional cerebral oxygen saturation to HMPAO SPECT
      study during balloon test occlusion.
AB  - BACKGROUND AND PURPOSE: To increase the reliability of 99mTc-hexamethyl
      propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT)
      study in the evaluation of hemodynamic change with balloon test occlusion (BTO)
      of the internal carotid artery, we attempted to clarify the usefulness of
      additional monitoring of regional oxygen saturation of the brain (rSO2). METHODS:
      During BTO, rSO2 monitoring with transcranial near infrared spectroscopy was
      performed 17 times on 16 patients. Asymmetrical distribution of the tracer was
      classified visually as follows: group 1, little or no asymmetry, and group 2,
      moderate or severe asymmetry. Seven regions of interest (ROI) were defined in the
      middle cerebral artery area of each hemisphere, and the asymmetry index
      (AI)=200x(Cnon-Coccl)/(Cnon+Coccl)), where Cnon=mean counts on the nonoccluded
      side, and Coccl=mean counts on the occluded side were also calculated. Then, mean
      AI (MAI) was obtained from AI of 7 ROIs for each study. RESULTS: Of the 17
      procedures, 10 BTOs were in group 1 and 5 BTOs were in group 2. Two patients did
      not undergo SPECT study because of the immediate appearance of a neurological
      deficit with BTO; they were defined as group 3. The MAI in group 1 was 2. 6+/
      3.3%, which was significantly smaller than the MAI in group 2 (25.6+/-5.0%,
      P<0.02). The DeltarSO2 (baseline rSO2-rSO2 during ICA occlusion) with BTO in
      group 1 was 1.5+/-1.4% (n=10), which was statistically smaller than that in group
      2 (5.5+/-1.3%, n=4, P<0.05). The DeltarSO2 in group 3 was 9.0+/-0.0% (n=2). In
      group 1, however, rSO2 began to decline when the stump pressure fell to 45 mm Hg
      and always declined when the stump pressure fell below 40 mm Hg. Furthermore, in
      group 1, a significant correlation was observed between the DeltarSO2 and stump
      pressure (r=0.85, P<0.0001). CONCLUSIONS: This preliminary study reveals that an
      obvious asymmetrical SPECT pattern always accompanies a profound decrease in rSO2
      and that rSO2 parallels a severe reduction in stump pressure in cases exhibiting
      a symmetrical SPECT pattern. Thus, the cerebral oximetry sensitively reflects the
      cerebral oxygenation, and simultaneous measurements of rSO2 and stump pressure
      with 99mTc-HMPAO SPECT study apparently are useful in evaluating hemodynamic
      integrity with BTO.

PMID- 9933281
TI  - Carpal tunnel syndrome involving unaffected limbs of stroke patients.
AB  - BACKGROUND AND PURPOSE: Stroke-induced hemiparesis involving the arm and hand
      results in regular, repeated overuse of the opposite hand and wrist. Because
      repetitive hand and wrist movement is a common cause of carpal tunnel syndrome
      (CTS), we examined the nonparetic upper limb in stroke patients for evidence of
      CTS. METHODS: We measured bilaterally sensory nerve conduction velocity (SNCV),
      motor nerve conduction velocity (MNCV), sensory nerve action potentials (SNAP) at
      the wrist, palm-to-wrist distal sensory latency (DSL), palm-to-wrist SNAP,
      compound motor action potentials (CMAP), and distal motor latency (DML) in stroke
      patients and control subjects. Controls were right-handed, >/=65 years old,
      lucid, independent in their activities of daily living, and had no disease known
      to cause CTS. Stroke patients were divided into a functioning hand group (n=61)
      and a disused hand group (n=71). All patients had hemiplegia. RESULTS: Tinel's
      sign was observed on the nonparetic side in 57.7% of patients with a disused hand
      and in 31.1% of those with a functioning hand. All electrophysiological indices
      were significantly more abnormal on the nonparetic side than on the hemiparetic
      side or in controls. Patients with a disused hand showed greater abnormality on
      the nonparetic side in SNCV, SNAP, palm-to-wrist DSL, DML, and CMAP than patients
      with a functioning hand. CONCLUSIONS: Overuse of the nonparetic hand and wrist of
      the nonparetic side may result in CTS in stroke patients, especially when the
      paretic hand is not functional. Wrist splinting or other prophylactic treatments
      beginning soon after stroke might help to prevent CTS.

PMID- 9933282
TI  - Gene transfer of human prostacyclin synthase prevents neointimal formation after
      carotid balloon injury in rats.
AB  - BACKGROUND AND PURPOSE: A disordered proliferative process in the vascular wall
      is thought to underlie the pathogenesis of restenosis after percutaneous
      transluminal angioplasty and carotid endarterectomy. A growth inhibitory property
      of overexpressed prostacyclin (PGI2) synthase (PGIS) was recently implicated in
      the pathological proliferation of vascular smooth muscle cells (VSMC) in vitro.
      Here, we investigated the effects of increased PGI2 synthesis on the pathological
      proliferation of VSMCs. METHODS: The cDNA encoding human PGIS was transfected
      into endothelium-denuded rat carotid arteries after arterial balloon injury with
      the use of hemagglutinating virus Japan (HVJ). HVJ liposome vector complex
      without PGIS cDNA was used for vehicle control. The level of 6-keto PGF1alpha, a
      stable hydrolyzed metabolite of PGI2, the histological distribution of the
      immunoreactivity for human PGIS and the ratio of neointimal/medial area were
      analyzed. RESULTS: In the analyses of 6-keto PGF1alpha, the level in the carotid
      arteries was significantly elevated 3 days after PGIS expression-vector
      transfection compared with that in the arteries after vehicle transfection. Seven
      days after human PGIS expression-vector transfection, the PGIS cDNA-transfected
      neointimal cells were strongly positive for human PGIS immunoreactivity in 81%
      sections examined. Fourteen days after the injury, the ratio of neointimal/medial
      area was 1.2+/-0.4 in the PGIS expression-vector transfected group, which was
      significantly smaller than that of the vehicle control group, 1.7+/-0.5; P<0.01.
      CONCLUSIONS: It was thus demonstrated that the gene transfer of human PGIS
      expression-vector into rat carotid arteries resulted in the increased production
      of human PGI2 in the vascular wall, the expression of human PGIS in the
      developing neointima and significantly inhibited the neointimal formation
      generated after balloon injury.

PMID- 9933283
TI  - Synergistic effects of a combination of low-dose basic fibroblast growth factor
      and citicoline after temporary experimental focal ischemia.
AB  - BACKGROUND AND PURPOSE: Basic fibroblast growth factor (bFGF) and citicoline
      (cytidine 5'-diphosphate choline, an endogenous compound that stabilizes membrane
      function) have demonstrated neuroprotective effects after focal cerebral
      ischemia. Both agents are candidates for future stroke therapy in humans. For
      evaluation of synergistic effects of bFGF and citicoline, a low-dose combination
      of both compounds was tested against each compound alone and placebo. METHODS:
      Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of focal
      cerebral ischemia with the use of the suture model of middle cerebral artery
      occlusion. Animals were randomly and blindly assigned to one of the following
      treatment groups: placebo, low-dose citicoline (250 mg/kg IP daily for 4 days),
      low-dose bFGF (10 microg/kg per hour IV for 3 hours), and the combination of both
      (250 mg/kg citicoline and 10 microg/kg per hour bFGF). Triphenyltetrazolium
      chloride staining was used after 4 days to determine postmortem infarction.
      Neurological scores were assessed on a daily basis. RESULTS: The premature
      mortality rate was 41.7% in the placebo and citicoline groups, 33.3% in the bFGF
      group, and 25% (P=NS) in the combination group. The mean neurological score on
      day 4 was 3.1+/-1.6 (placebo), 3.1+/-1.6 (citicoline), 2.9+/-1.5 (bFGF), and
      2.4+/-1.4 (combination) (P=NS). The mean volume of infarction was significantly
      reduced in the combination group (136. 5+/-25.4 mm3) versus placebo (172.6+/-48.9
      mm3; P=0.036, Fisher test), versus citicoline alone (186.0+/-35.7 mm3; P=0.005,
      Fisher test), and versus bFGF alone (176.0+/-49.2 mm3; P=0.023, Fisher test).
      CONCLUSIONS: These results demonstrate synergistic effects of a low-dose
      combination of the growth factor bFGF and citicoline after temporary experimental
      focal cerebral ischemia and furthermore support the effectiveness of a
      combination treatment regimen for the management of acute stroke.

PMID- 9933284
TI  - Inhibition of ischemia-induced glutamate release in rat striatum by dihydrokinate
      and an anion channel blocker.
AB  - BACKGROUND AND PURPOSE: Increased activation of excitatory amino acid (EAA)
      receptors is considered a major cause of neuronal damage. Possible sources and
      mechanisms of ischemia-induced EAA release were investigated pharmacologically
      with microdialysis probes placed bilaterally in rat striatum. METHODS: Forebrain
      ischemia was induced by bilateral carotid artery occlusion and controlled
      hypotension in halothane-anesthetized rats. During 30 minutes of ischemia,
      microdialysate concentrations of glutamate and aspartate were measured in the
      presence of a nontransportable blocker of the astrocytic glutamate transporter
      GLT-1, dihydrokinate (DHK), or an anion channel blocker, 4,4'-dinitrostilben-2,2'
      disulfonic acid (DNDS), administered separately or together through the dialysis
      probe. RESULTS: In control striata during ischemia, glutamate and aspartate
      concentrations increased 44+/-13 (mean+/-SEM) times and 19+/-5 times baseline,
      respectively, and returned to baseline values on reperfusion. DHK (1 mmol/L in
      perfusate; n=8) significantly attenuated EAA increases compared with control
      (glutamate peak, 9. 6+/-1.7 versus control, 15.4+/-2.6 pmol/ microL). EAA levels
      were similarly decreased by 10 mmol/L DHK. DNDS (1 mmol/L; n=5) also suppressed
      EAA peak increases (glutamate peak, 5.8+/-1.1 versus control, 10.1+/-0.7 pmol/
      microL). At a higher concentration, DNDS (10 mmol/L; n=7) further reduced
      glutamate and aspartate release and also inhibited ischemia-induced taurine
      release. Together, 1 mmol/L DHK and 10 mmol/L DNDS (n=5) inhibited 83% of EAA
      release (glutamate peak, 2.7+/-0.7 versus control, 10.9+/-1.2 pmol/ microL).
      CONCLUSIONS: These findings support the hypothesis that both cell swelling
      induced release of EAAs and reversal of the astrocytic glutamate transporter are
      contributors to the ischemia-induced increases of extracellular EAAs in the
      striatum as measured by microdialysis.

PMID- 9933285
TI  - Reduction of apurinic/apyrimidinic endonuclease expression after transient global
      cerebral ischemia in rats: implication of the failure of DNA repair in neuronal
      apoptosis.
AB  - BACKGROUND AND PURPOSE: To clarify the relationship between apurinic/apyrimidinic
      endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision
      repair pathway, and delayed neuronal cell death associated with apoptosis, we
      examined the expression of APE/Ref-1 before and after transient global ischemia
      in rats. METHODS: Global ischemia was induced by bilateral common carotid artery
      occlusion and hypotension. Expression of the APE/Ref-1 protein was evaluated by
      Western blot and immunohistochemical analyses. Apoptosis after global ischemia
      was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase
      mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining.
      RESULTS: Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the
      control brains. Nuclear immunoreactivity of APE/Ref-1 was significantly decreased
      2 days after 10 minutes of ischemia in the hippocampal CA1 subregion. Western
      blot analysis of a sample from the normal brains showed a characteristic 37-kDa
      band, which was reduced in the hippocampal CA1 subregion after ischemia. A
      significant amount of DNA fragmentation was observed at 3 days but not at 1 day
      after ischemia. Double staining with APE/Ref-1 and TUNEL clearly showed that the
      neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive. CONCLUSIONS:
      Our data provide evidence that APE/Ref-1 decreased in hippocampal CA1 neurons
      after transient global ischemia and that this reduction precedes DNA
      fragmentation, which is destined to cause apoptosis. Our results suggest the
      possibility that a decrease of APE/Ref-1 activity and the failure of DNA repair
      may underlie the mechanism of apoptosis after transient focal ischemia.

PMID- 9933286
TI  - Effects of tirilazad mesylate on vasospasm and phospholipid hydroperoxides in a
      primate model of subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Tirilazad mesylate has been used in the attempt to
      prevent cerebral vasospasm after subarachnoid hemorrhage (SAH), although the
      actual targets of this agent in vivo have thus far been controversial.
      Chemiluminescence/high-performance liquid chromatography provided a new method
      for direct measurements of phosphatidylcholine hydroperoxide (PCOOH) and
      phosphatidylethanolamine hydroperoxide (PEOOH) in vivo and showed that
      phosphatidylcholine is the lipid class most susceptible to lipid peroxidation. In
      the present study we measured those levels in a primate model of SAH for
      determination of the effects of tirilazad on vasospasm. METHODS: Fourteen Macaca
      monkeys of both sexes were randomly assigned into 2 groups: a tirilazad group
      receiving a dosage of 0.3 mg/kg and a placebo group receiving only the vehicle in
      which tirilazad was delivered. After the induction of experimental SAH around the
      right middle cerebral artery on day 0, tirilazad or vehicle was administered
      intravenously every 8 hours for 6 days. On day 7, the animals were killed after
      angiography and regional cerebral blood flow measurements were performed. The
      levels of PCOOH and PEOOH were measured in the clots, bilateral parietal
      cortices, right frontal cortex contact with clots, cerebellar hemispheres,
      bilateral middle cerebral arteries, and basilar arteries. RESULTS: In the placebo
      group, a significant vasospasm occurred in the cerebral arteries on both sides,
      but most prominently on the right side. The degree of vasospasm in the cerebral
      arteries was significantly attenuated in the tirilazad group (P<0.005). There
      were no significant differences in regional cerebral blood flow, PCOOH, and PEOOH
      levels in the clots, cerebral cortices, and cerebellar hemispheres between the 2
      groups. In contrast, the levels of PCOOH in the cerebral arteries were
      significantly higher in the placebo group than in the tirilazad group (P<0.025).
      It was remarkable that the tirilazad treatments eliminated PCOOH in any vascular
      territory after SAH. CONCLUSIONS: PCOOH in the artery wall may be an important
      indicator for vasospasm, and the inhibition of PCOOH may explain the efficacy of
      tirilazad on vasospasm.

PMID- 9933287
TI  - Brain stem MRI signal abnormalities in CADASIL.
AB  - BACKGROUND: We recently showed that the severity of MRI signal abnormalities
      increases with age in CADASIL, an arteriopathy due to mutations of notch 3 gene
      on chromosome 19. Previous results also suggest that the various hemispheric
      subcortical areas have a different vulnerability to ischemia in this disease. The
      distribution of the lesions at the brain stem level has not yet been reported.
      CASE DESCRIPTIONS: We reviewed the MRIs of 68 affected patients having signal
      abnormalities in the hemispheric white matter to assess the distribution and
      clinical consequences of brain stem signal abnormalities in CADASIL. We found
      hypersignals on T2-weighted images in the brain stem in 45% of the subjects. The
      pons was more frequently involved (100%) than the mesencephalon (69%) and the
      medulla (35%). Hyposignals on T1-weighted images, at the brain stem level, were
      observed only in two thirds of these subjects. The lack of signal abnormalities
      reaching the brain stem surface and the absence of cerebellar lesions were
      noteworthy. CONCLUSIONS: Brain stem signal abnormalities observed in CADASIL are
      found in regions irrigated only by perforating arteries. These results support
      parallel observations made for CADASIL-associated signal abnormalities in the
      cerebral hemispheres and emphasize the importance of the angioarchitecture of the
      cerebral vasculature to explain why a condition characterized by a systemic
      vessel wall pathology is manifested only as a brain disease.

PMID- 9933288
TI  - Neurochemical monitoring of fatal middle cerebral artery infarction.
AB  - BACKGROUND: Microdialysis is a method for neurochemical monitoring that has been
      applied more frequently over the past few years in patients suffering from
      subarachnoid hemorrhage, acute brain injury, and stroke. It is used to study the
      course of extracellular molecules of low molecular weight, such as excitatory
      amino acids or metabolic end products. CASE DESCRIPTION: We report the case of a
      43-year-old patient suffering from left hemispheric stroke with a space-occupying
      postischemic edema leading to a considerable mass effect on the contralateral
      side. For treatment of severe edema, hypothermia was initiated. The microdialysis
      and intracranial pressure probe were placed into the noninfarcted hemisphere. A
      massive increase in levels of glutamate, glycerine, and the lactate-pyruvate
      ratio was measured 24 hours before intracranial pressure elevation was observed
      and brain death occurred. CONCLUSIONS: Monitoring excitatory amino acids,
      glycerine as a membrane component, and lactate-pyruvate ratio as an energy marker
      by microdialysis is a useful tool to increase our understanding of biochemical
      events in secondary brain damage. For future prevention of secondary ischemia in
      patients with massive stroke, close neurochemical monitoring might be valuable to
      improve therapy, particularly in the critically ill.

PMID- 9933289
TI  - "Telestroke" : the application of telemedicine for stroke.
AB  - BACKGROUND: Time is of the essence for effective intervention in acute ischemic
      stroke. Efforts including stroke teams that are "on call" around-the-clock are
      emerging to reduce the time from emergency room arrival to evaluation and
      treatment. SUMMARY OF COMMENT: Based on the results of the NINDS rt-PA Stroke
      Trial, which demonstrated both clinical effectiveness in reducing neurological
      deficits and disability and cost savings to health care systems, many community
      hospitals and managed-care organizations are exploring methods to enhance and
      expedite acute stroke care in their local communities. Only a small fraction of
      acute stroke victims is currently treated with thrombolytics (<1.5% nationally),
      and few benefit from the expertise and experience of the stroke teams. It is
      essential to develop new paradigms to improve acute stroke care in all settings,
      rural and urban. Rapid linkages to expert stroke care can help the underserved
      areas. Telemedicine for stroke, "Telestroke, " uses state-of-the-art video
      telecommunications that may be a potential solution and may maximize the number
      of patients given effective acute stroke treatment across the country and across
      the world. Telestroke could facilitate remote cerebrovascular specialty consults
      from virtually any location within minutes of attempted contact, adding greater
      expertise to the care of any individual patient. This model also has the
      potential to enhance patient entry into clinical trials. Telestroke would enhance
      stroke education through the use of Internet-based interactives for health-care
      professionals and patients. Education would be facilitated through the creation
      of telecommunication-linked classes providing interactive information on stroke
      care and prevention to places where they are otherwise not available. Health-care
      professionals will gain experience and expertise through the interaction with a
      remote expert--telementoring. Telestroke provides an excellent medium for data
      collection and an unprecedented opportunity for quality assurance. Monitoring of
      an entire tele-interaction can offer real-time assessments, which can then be
      analyzed in-depth at a later date for unique insights into health-care delivery.
      Prehospital use of telemedicine for stroke is already being piloted, linking
      patients in the ambulance to the emergency department. Legal and economic
      parameters must be established for telemedicine in the areas of reimbursement,
      liability, malpractice insurance, licensing, and credentialing. Issues of
      protection of privacy and confidentiality, informed consent, product liability,
      and industry standards must be addressed to facilitate the use of this new and
      potentially useful technology. CONCLUSIONS: Computer-based technology can now be
      used to integrate electronic medical information, clinical assessment tools,
      neuroradiology, laboratory data, and clinical pathways to bring state-of-the-art
      expert stroke care to underserved areas.

PMID- 9933290
TI  - Treatment of intracranial aneurysms by embolization with coils: a systematic
      review.
AB  - BACKGROUND: Embolization with coils is increasingly used for the treatment of
      intracranial aneurysms. To assess the percentage of complications, the percentage
      of aneurysm occlusion, and the short-term outcome, we performed a systematic
      review of studies on embolization with controlled detachable or pushable coils.
      SUMMARY OF REVIEW: To find studies on embolization with coils, we performed a
      MEDLINE search from January 1990 to March 1997, checked all reference lists of
      the studies found, performed a Science Citation Index search on Guglielmi, and
      hand searched recent volumes of 25 journals. Two authors independently extracted
      data by means of a standardized data extraction form from 48 eligible studies
      totalling 1383 patients. Permanent complications of embolization with controlled
      detachable coils occurred in 46 of 1256 patients (3.7%; 95% CI, 2.7% to 4.9%);
      400 of 744 aneurysms (54%; 95% CI, 50% to 57%) were completely occluded. By means
      of weighted linear regression, no relation between baseline characteristics and
      outcome measurements was found. The results in the prespecified subgroups of
      patients with a ruptured aneurysm, an unruptured aneurysm, or a basilar
      bifurcation aneurysm were essentially the same as the overall results.
      CONCLUSIONS: Short-term results indicate that embolization with coils is a
      reasonably safe treatment for patients with an unruptured aneurysm and for
      patients with aneurysmal subarachnoid hemorrhage. The effectiveness in terms of
      complete occlusion of the aneurysm is moderate. Randomized trials are warranted
      to compare surgical clipping with embolization with coils.

PMID- 9933291
TI  - Acute cerebral infarction caused by aortic dissection: caution in the
      thrombolytic era.

PMID- 9933292
TI  - Diffusion-weighted MRI in severe leukoaraiosis.

PMID- 9933293
TI  - Abstracts of literature 

PMID- 9933294
TI  - The following is a list of major ongoing studies about stroke. Information about
      other multicenter studies that might be included in this list should be submitted
      to the stroke editorial office by the principal investigator. The list will
      appear in the february, june, and october issues of stroke 

PMID- 9933295
TI  - Dentatorubral-pallidoluysian atrophy or Naito-Oyanagi disease.
AB  - Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant
      cerebellar ataxia characterized clinically by myoclonus, epilepsy, cerebellar
      ataxia, choreoathetosis, and dementia with personality change.
      Histopathologically, DRPLA is characterized by a unique combination of
      degenerative changes in both the dentatofugal and the pallidofugal systems.
      Credit for the establishment of DRPLA as an entity is given to Naito and Oyagagi,
      who first noticed a strong heritability and an age of onset-dependent variability
      of the clinical features. Most papers on DRPLA research are written in Japanese,
      and are extensively reviewed here. After the gene was identified in 1994, DRPLA
      became known as one of the CAG repeat expansion diseases, in which the
      responsible gene is located on chromosome 12p and its product is called atrophin
      1. Classical genetics revealed that DRPLA shows prominent "anticipation" and
      modern molecular genetics provided a clear explanation for this phenomenon, by
      demonstrating a strong instability of the expanded CAG repeat length through
      generations. The impact of gene analysis of DRPLA on the clinical genetics and
      neurology are discussed. Moreover, possible mechanism(s) underlying the neuronal
      cell death in DRPLA are discussed in terms of the molecular pathology.

PMID- 9933296
TI  - Fine localization of the CMT4A locus using a PAC contig and haplotype analysis.
AB  - Charcot-Marie-Tooth disease type 4A (CMT4A) is a severe, autosomal recessive
      peripheral neuropathy linked to chromosome 8q13-q21. We have previously
      constructed a YAC contig across the CMT4A region and narrowed the disease
      flanking interval to approximately three megabases. Subsequently, we constructed
      a PAC/BAC contig made of 44 clones and mapped 44 new and 30 previous STSs, ESTs,
      and polymorphic makers to the region. Using 13 polymorphic markers, we have now
      identified an ancestral haplotype segregating in three families, indicating a
      common founder mutation. Two ancestral recombination events in this haplotype
      significantly reduce the minimal candidate region to a minimal trailing path of
      five PAC/BAC clones, which will now allow direct investigation of candidate genes
      for CMT4A.

PMID- 9933297
TI  - HLA typing in the United Kingdom multiple sclerosis genome screen.
AB  - The United Kingdom multiple sclerosis genome screen demonstrated a peak maximum
      lod score of 2.8 in the HLA region, together with statistically significant
      excess transmission of the 121-base pair (bp) allele of the tumour necrosis
      factor-a marker. In order to determine whether this association is independent of
      the established HLA association, or simply a consequence of the 121-bp allele
      being part of the same haplotype, we HLA-DR and -DQ typed the 227 sibling-pair
      families used in the original screen. The expected associations of multiple
      sclerosis with the DR15 (p=8.7E-18), DQ6 (p=2.0E-09) and DR51 (p=2.8E-16)
      phenotypes were confirmed, and excess transmission of the DRB1*1501 and DQB1*0602
      alleles was demonstrated. Combining HLA typing with the original microsatellite
      data demonstrated extensive linkage disequilibrium between the 121-bp allele and
      the 1501-0602 haplotype. Outside this extended haplotype (121-1501-0602), none of
      the alleles demonstrated significant transmission distortion. Having established
      the importance of this extended haplotype, we reanalysed the entire genome screen
      data after excluding those sibling pairs sharing the extended haplotype (n=27).
      Conditioning the full genome screen data on the basis of identity by state
      sharing showed that some potential linkage regions identified in the original
      screen clustered in families, in which the extended haplotype was shared (1p, 2p
      and 17q), whereas others grouped with those in which it was not (5cen, 7p and
      Xq). This suggests complexity in the genetics of multiple sclerosis.

PMID- 9933298
TI  - Refined mapping and characterization of the recessive familial amyotrophic
      lateral sclerosis locus (ALS2) on chromosome 2q33.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular
      disease that shows familial, autosomal dominant inheritance in 10%-15% of cases.
      Previous genetic analysis of one large family linked a recessive form of familial
      ALS (FALS-AR type 3) to the chromosome 2q33-35 region. Using additional
      polymorphic markers, we have narrowed the size of the linked region to
      approximately 1.7 cM by linkage and haplotype analysis. We have also established
      a yeast artificial chromosome contig across the locus that covers an approximate
      physical distance of 3 million bases. Based on this contig, genes and expressed
      sequences that map near the 2q33 region have been examined to determine whether
      they are located within this ALS2 candidate locus. Five identified genes and 34
      expressed sequence tags map within the region defined by crossover analysis and
      merit further consideration as candidate genes for this disease.

PMID- 9933299
TI  - Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to
      pressure palsies: a SacI polymorphism in the proximal CMT1A-REP elements may lead
      to genetic misdiagnosis.
AB  - A male patient with clinical signs and symptoms of a demyelinating neuropathy was
      shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2 by means
      of two-color fluorescence in situ hybridization (FISH). This duplication is
      typical for the vast majority of Charcot-Marie-Tooth type 1A (CMT1A) cases.
      Analysis of DNA extracted from peripheral blood used to detect an EcoRI/SacI 3. 2
      kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication, but also
      revealed a 7.8-kb fragment usually observed in patients with a hereditary
      neuropathy with liability to pressure palsies (HNPP). Both fragments observed in
      one patient canot result from one unequal crossover. In EcoRI/SacI Southern
      hybridization experiments with probe pLR7.8 DNA of his healthy parents also
      revealed a 7.8-kB restriction fragment. A subsequent two-color FISH analysis,
      however, indicated a normal status for interphase nuclei of the parents. Hence we
      hypothesize that the 7.8-kb fragment observed in our patient and his parents is
      not the product of unequal crossover during meiosis but due to a polymorphism of
      the SacI site in a proximal CMT1A-REP element.

PMID- 9933300
TI  - Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene:
      evaluation of its involvement in idiopathic generalized epilepsy.
AB  - Neurophysiological and pharmacological studies suggest a major role of the GABAB
      receptor in the epileptogenesis of absence seizures. The gene encoding the human
      GABABR1 receptor (GABABR1) has recently been mapped to human chromosome 6p21.3 by
      in situ hybridization, a region that harbors a susceptibility locus (EJM1) for
      idiopathic generalized epilepsy (IGE). We investigated the hypothesis that the
      GABABR1 gene (GABBR1) represents a candidate gene for EJM1 by: (1) defining the
      precise localization approximately 130 kilobases telomeric to the HLA-F locus,
      (2) by characterizing its genomic organization, and (3) by mutation screening of
      the entire coding region of GABBR1 in 18 German patients with juvenile myoclonic
      epilepsy (JME) who were derived from families with evidence for linkage to
      chromosome 6p21.3 (cumulative lod score Z=3.17 at HLA-DQ). The GABAB receptor
      gene consists of 22 translated exons. The two alternative transcripts, GABABR1a
      and GABABR1b, are derived from the same locus but they differ in their
      alternative 5'-exons. Mutation analyses in JME revealed several DNA sequence
      polymorphisms, two of which result in amino acid changes occurring in all IGE
      affected members of two families. However, clinically unaffected relatives did
      carry the same variations, excluding these amino acid substitutions as the cause
      for IGE in these families.

PMID- 9933301
TI  - Linkage of a commoner form of recessive amyotrophic lateral sclerosis to
      chromosome 15q15-q22 markers.
AB  - Autosomal recessive familial amyotrophic lateral sclerosis (RFALS) is a rare form
      of ALS that usually presents at an early age with slow progression of symptoms.
      RFALS is clinically and genetically heterogeneous and the locus of RFALS type 3
      was mapped to 2q33 (ALS2) in a single family. We now report linkage of a more
      common form of RFALS to chromosome 15q15-q22 markers (ALS5) and show further
      genetic locus heterogeneity in RFALS. ALS5 is the locus for most families with
      RFALS and appears to be present in both North African and European populations.

PMID- 9933303
TI  - The NF2 gene and merlin protein in human osteosarcomas.

PMID- 9933302
TI  - Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to
      hyperactivity and suggest a link with cholinergic transmission.
AB  - Mutations in the human dystrophin gene cause Duchenne muscular dystrophy, a
      common neuromuscular disease leading to a progressive necrosis of muscle cells.
      The etiology of this necrosis has not been clearly established, and the cellular
      function of the dystrophin protein is still unknown. We report here the
      identification of a dystrophin-like gene (named dys-1) in the nematode
      Caenorhabditis elegans. Loss-of-function mutations of the dys-1 gene make animals
      hyperactive and slightly hypercontracted. Surprisingly, the dys-1 mutants have
      apparently normal muscle cells. Based on reporter gene analysis and heterologous
      promoter expression, the site of action of the dys-1 gene seems to be in muscles.
      A chimeric transgene in which the C-terminal end of the protein has been replaced
      by the human dystrophin sequence is able to partly suppress the phenotype of the
      dys-1 mutants, showing that both proteins share some functional similarity.
      Finally, the dys-1 mutants are hypersensitive to acetylcholine and to the
      acetylcholinesterase inhibitor aldicarb, suggesting that dys-1 mutations affect
      cholinergic transmission. This study provides the first functional link between
      the dystrophin family of proteins and cholinergic transmission.

PMID- 9933304
TI  - Transcript map of the chromosome 2-linked autosomal dominant spastic paraplegia
      (SPG4) critical region and identification of a highly informative STRP.

PMID- 9933305
TI  - Toxicokinetics of pyrethroids in humans: consequences for biological monitoring.

PMID- 9933306
TI  - Method for analyzing urinary toluene and xylene by solid-phase microextraction
      (SPME), and its application to workers using organic solvents.

PMID- 9933307
TI  - Chromosome aberrations study in human lymphocytes from marijuana smokers.

PMID- 9933308
TI  - Small-scale spatial variation of selenium concentrations in Chironomid larvae.

PMID- 9933309
TI  - Differences in reproductive characteristics among field populations of Polycelis
      tenuis (Platyhelminthes) in a metal contaminated stream.

PMID- 9933310
TI  - Fractioning of Cu, Mn, Zn, and Pb in mineral soils along an oak forest vegetation
      gradient in Mexico City.

PMID- 9933311
TI  - Heavy metal removal by microalgae.

PMID- 9933312
TI  - Heavy metals in the shrimp Xiphopenaeus kroyeri (Heller, 1862) (Crustacea,
      penaeidae) from Ubatuba Bay, Sao Paulo, Brazil.

PMID- 9933313
TI  - Copper and lead accumulation in tissues of a freshwater fish Tilapia zillii and
      its effects on the branchial Na,K-ATPase activity.

PMID- 9933314
TI  - Arsenic induced liver hyperplasia and kidney fibrosis in rainbow trout
      (Oncorhynchus mykiss) by microinjection technique: A sensitive animal bioassay
      for environmental metal-toxicity.

PMID- 9933316
TI  - Nitrate and nitrite accumulation in fresh vegetables from Greece.

PMID- 9933315
TI  - Physiological and biochemical response of Scenedsmus obliquus to combined effects
      of Al, Ca, and low pH.

PMID- 9933317
TI  - Effects of DDVP, naphthalene, and cadmium on intestinal proteolytic activity in
      Mozambique tilapia (Oreochromis mossambicus Peters).

PMID- 9933318
TI  - Organochlorine pesticides in water, sediment, and fish of Paranoa Lake of
      Brasilia, Brazil.

PMID- 9933319
TI  - Inhibition of glutathione S-transferase catalyzed xenobiotic detoxication by
      organotin compounds in tropical marine fish tissues.

PMID- 9933321
TI  - Effect of zeolite on the reduction of cadmium toxicity in water and a freshwater
      fish, Oreochromis mossambicus.

PMID- 9933320
TI  - Evaluation of selected endocrine disrupting compounds on sex determination in
      Daphnia magna using reduced photoperiod and different feeding rates.

PMID- 9933322
TI  - Susceptibility of embryonic and larval African catfish (Clarias gariepinus) to
      toxicants.

PMID- 9933323
TI  - Ascariasis of the gallbladder: radiological evaluation and follow-up.

PMID- 9933324
TI  - Your research: how to get it on paper and in print.
AB  - Much worthwhile medical research is never accepted for publication or is ignored
      when published, often because it is poorly presented. The purpose of this article
      is to express in simple language how research is best presented in writing. Few
      actual data are given, though much experience is summarized. The result desired
      is greater ease, clarity, and effectiveness in communicating medical research.
      The principles presented here are intended to make medical research writing
      easier and clearer and to give the research itself more impact.

PMID- 9933325
TI  - Lung abscess versus necrotizing pneumonia: implications for interventional
      therapy.
AB  - OBJECTIVE: To assess and contrast the role of interventional therapy for two
      types of cavitating pneumonias: lung abscess and necrotizing pneumonia. MATERIALS
      AND METHODS: We retrospectively reviewed the imaging, interventional therapy, and
      outcome of 14 children seen between February 1987 and January 1996 with lung
      abscess and 9 with necrotizing pneumonia. All children were treated with
      antibiotics prior to intervention. Pulmonary parenchymal fluid was percutaneously
      aspirated from ten lung abscesses and three necrotizing pneumonias. Percutaneous
      catheters drained five lung abscesses. Pleural drainage was performed for three
      lung abscesses and eight necrotizing pneumonias. RESULTS: All 14 children with
      lung abscesses had positive Gram stains of the pulmonary fluid; 13 cultures were
      positive. All 14 defervesced within 48 h of intervention. None developed a
      bronchopleural fistula. All nine necrotizing pneumonias were presumed to be
      sequelae of prior pneumonia. Streptococcus pneumoniae was the only organism as
      documented by pleural fluid latex fixation in three patients, gram stain in two,
      and culture in only one. Seven of these children developed pneumatoceles, five
      developed bronchopleural fistulae, and three required long-term chest tubes for
      persistent pneumothoraces. CONCLUSION: Aggressive interventional therapy can be
      diagnostic and therapeutic in the infected lung abscess. Interventional therapy
      can be harmful in postinfectious necrotizing pneumonia.

PMID- 9933326
TI  - Prenatal detection of a solitary liver adenoma.
AB  - Solitary liver adenomas are rare in children, especially in neonates, and can be
      difficult to distinguish from other more common liver tumors of newborns and
      infants. An otherwise healthy male neonate with a prenatal diagnosis of a liver
      mass underwent ultrasound and MRI followed by resection of the mass. The final
      histopathological diagnosis was hepatic adenoma. A discussion of the imaging
      evaluation, differential diagnosis, and literature review is presented.

PMID- 9933327
TI  - Worsening enterocolitis in neonates: diagnosis by CT examination of urine after
      enteral administration of iohexol.
AB  - Perforation, a severe complication of necrotizing enterocolitis (NEC), has a high
      mortality rate. Recently, we presented a new technique for evaluation of NEC:
      measuring the CT attenuation coefficient of urine after oral administration of
      iohexol. We present three cases of neonates with NEC who demonstrated serial
      increases in urine CT attenuation coefficients, all of whom subsequently
      deteriorated clinically and radiographically. Surgery in all three cases
      confirmed severe necrosis and/or perforation. These three cases suggest that the
      CT attenuation coefficient of urine after oral administration of iohexol may be a
      more sensitive indicator of NEC severity, progression, and perforation than
      clinical evaluation and radiography. More investigation is necessary, but
      eventually, this noninvasive technique may be able to decrease morbidity and
      mortality by predicting the need for surgical intervention or more aggressive
      medical management of NEC before perforation occurs.

PMID- 9933328
TI  - Metanephric adenoma of the kidney: a case report.
AB  - Metanephric adenoma (MA) of the kidney is an uncommon benign epithelial tumor of
      the kidney that presents at any age. The histology of the lesion is well
      established, but the imaging findings have been described in only a few cases. We
      report the sonographic and computed tomographic appearance of MA in a 9-year-old
      girl to increase awareness among radiologists of this entity. Its recognition may
      facilitate nephron-sparing surgery.

PMID- 9933329
TI  - The kidney in children with tyrosinemia: sonographic, CT and biochemical
      findings.
AB  - BACKGROUND: Tyrosinemia relates to a deficiency of fumarylacetoacetate hydrolase
      and presents early in life with central nervous system and liver abnormalities.
      Renal function is often impaired. Little is known about the architecture and
      function of the kidneys. OBJECTIVE: Imaging changes on US and CT are compared to
      the function of the kidneys in children with tyrosinemia, and followed after
      liver transplantation. MATERIALS AND METHODS: Renal sonography, CT and renal
      function tests in 32 children were reviewed. Renal length, volume, echogenicity
      and nephrocalcinosis were evaluated. Renal function was assessed by glomerular
      filtration rate, and the presence of aminoaciduria, acidosis and calciuria.
      Seventeen children had open renal biopsy during time of liver transplantation.
      Histology was reviewed. Statistical analyses relating renal structure to function
      were performed, and repeated after transplantation. RESULTS: The kidneys were
      enlarged (47 %), hyperechogenic (47 %) and showed nephrocalcinosis (16 %). There
      was delayed excretion of contrast medium at CT in 64 %. Aminoaciduria was present
      in 82 % of children, hypercalciuria in 67 %, tubular acidosis in 59 %, and low
      GFR in 48 %. Delayed excretion of contrast was associated with low GFR (P <
      0.05). Renal biopsies showed dilated tubules (81 %), interstitial fibrosis (56
      %), glomerulosclerosis (56 %) and tubular atrophy (56 %). During a mean
      observation period of 3 years following liver transplantation, GFR improved in 50
      %, tubular acidosis in 50 % and hypercalciuria in 70 %. No change was noted in
      renal size or sonographic architecture. CONCLUSION: Renal architecture and
      function are abnormal in the majority of children with tyrosinemia. Liver
      transplantation improves renal function in about 50 % of patients, but abnormal
      renal size and architecture persist.

PMID- 9933330
TI  - Popliteal entrapment syndrome: non-invasive diagnosis and complete recovery after
      surgery in an 11-year-old boy.
AB  - We present an unusual case of popliteal entrapment syndrome type I in an 11-year
      old boy. Presenting symptoms were exercise-related pain and pallor in his left
      lower leg. The diagnosis of popliteal entrapment syndrome was established by
      acral plethysmography, colour-coded Doppler sonography and MRI. After myotomy of
      the gastrocnemius muscle the symptoms resolved completely. Post-operative duplex
      scan showed normal blood flow, even in plantar flexion of the foot.

PMID- 9933331
TI  - Aggressive manifestations of inflammatory pulmonary pseudotumor in children.
AB  - We present three cases that illustrate the locally invasive radiographic
      appearance that inflammatory pulmonary pseudotumor can assume. Awareness and
      inclusion of inflammatory pseudotumor in the differential diagnosis of aggressive
      pleuropulmonary and mediastinal processes may have critical treatment
      implications.

PMID- 9933332
TI  - Correlation between clinical and ultrasound assessment of the knee in children
      with mono-articular or pauci-articular juvenile rheumatoid arthritis.
AB  - BACKGROUND: Ultrasonography of the knee is a non-invasive, readily available and
      low-cost tool for demonstrating peri-articular tissues. OBJECTIVE: To correlate
      clinical features with US findings in the detection, quantification and follow-up
      of inflammatory signs of the knee in children with pauci-articular juvenile
      rheumatoid arthritis (JRA). MATERIALS AND METHODS: US of both knees was performed
      in 49 patients on the same day as the clinical examination. All joints were
      classified into two groups by clinical criteria: group A (active disease) or
      group B (quiescent disease). Thirteen patients underwent one or more follow-up
      examinations. US was performed with a small-parts, 7.5-MHz, electronic linear
      probe by using a technique previously reported. Quantitative assessment of any
      effusion and synovial thickening was evaluated at the level of the suprapatellar
      bursa. Wilcoxon and Spearman tests were employed to compare US findings between
      the two groups and to correlate clinical and US findings within each group,
      respectively. RESULTS: US demonstrated significant increase of effusion and
      synovial thickening in group A joints. US enabled visualisation of clinically
      undetected popliteal cysts in three patients. Correlation between clinical and US
      findings was significant in group A and positive, though not significant, in
      group B. CONCLUSIONS: US seems to be a sensitive and reliable method for the
      assessment and monitoring of knee joint involvement in pauci-articular JRA.

PMID- 9933333
TI  - Hereditary Gottron's acrogeria with recessive transmission: a report of four
      cases in one family.
AB  - Four cases of acrogeria in one large family with multiple consanguineous
      marriages are reported. Inheritance is autosomal recessive. Evaluation of six
      generations of this family also showed six individuals with congenital blindness;
      this pedigree suggests autosomal recessive inheritance also for this disorder.
      Association of the two conditions was not seen in living members. The initial
      presentation in the patients with acrogeria was failure of growth during the
      first year of life, accompanied by characteristic facial appearance and cutaneous
      atrophy of the face and extremities. The radiologic features of these patients
      were acro-osteolysis, wide sutures and fontanelles, wormian bones, mandibular
      hypoplasia and avascular necrosis of the femoral heads. Other features were
      osteolysis of the clavicles, soft tissue calcification, osteoporosis and coxa
      valga, which have not been described in previous reported cases.

PMID- 9933334
TI  - Ischio-vertebral dysplasia: a distinct entity.
AB  - BACKGROUND: Kyphoscoliosis is a complication of some bone dysplasias, including
      cleidocranial dysplasia. OBJECTIVES: We report a distinct disorder with defective
      ossification of the ischial rami, severe kyphoscoliosis and normal clavicles.
      Early recognition of this syndrome allows prevention of complications. MATERIALS
      AND METHODS: All patient cases (aged 1 day to 33 years) were selected according
      to the above criteria, with special attention to radiological findings, family
      history and follow-up (5-30 years). RESULTS: In all eight patients, we observed
      the following: (a) Severe thoracic scoliosis of early onset and rapid
      progression, leading to rotatory dislocation. Spinal cord compression occurred in
      four cases with respiratory problems related to chest deformity. (b) Bilateral
      and symmetrical incomplete ossification of the ischial rami. (c) Peculiar facies
      with retrognathia. (d) Normal clavicles. Three patients were from the same family
      (grandmother, mother and daughter). CONCLUSION: Ischio-vertebral dysplasia seems
      to represent a true entity, with radiological and genetic findings that make it
      distinct from cleidocranial dysostosis. The association of kyphoscoliosis and
      these pelvic abnormalities is specific for this condition. Neurological and
      respiratory complications can be avoided if the condition is recognised early and
      early treatment is instituted.

PMID- 9933335
TI  - Calcified leiomyoma of deep soft tissue in a child.
AB  - We report the case of a 7-year-old boy with a calcified leiomyoma in the right
      gluteal muscle. Radiography and CT showed a well-defined soft tissue mass with
      mulberry-like calcifications that superficially resembled chondroid matrix
      calcification. The mass exhibited high-signal intensity intermingled with spotty
      low-signal intensity on T2-weighted MRI which was attributable to extensive non
      malignant degeneration of the tumour.

PMID- 9933337
TI  - Cervical lung protrusions in children.

PMID- 9933338
TI  - Cavernous angioma: a cryptic CT and MRI presentation.

PMID- 9933336
TI  - Glutaric aciduria type I: ultrasonographic demonstration of early signs.
AB  - BACKGROUND: Glutaric aciduria type I (GA-I) is a rare inherited metabolic disease
      with increased excretion of glutaric acid and its metabolites. Diagnosis is often
      delayed until the onset of irreversible neurological deficits. MATERIAL AND
      METHODS: We reviewed the clinical and imaging (US, CT and MRI) findings in six
      patients with proven GA-I and with emphasis on the early US findings. Coronal and
      sagittal US images of the brain were obtained through the anterior fontanelle in
      all patients. CT was obtained in three patients and MRI was obtained in two.
      RESULTS: Macrocephaly was found in all patients, being present in three children
      at birth or developing rapidly within the first weeks of life. US showed, in all
      patients, bilateral symmetrical cyst-like dilatation of the sylvian fissures.
      Progressive fronto-temporal atrophy developed within the first months. CT and MRI
      demonstrated fronto-temporal atrophy with lack of opercularisation in all cases
      and basal ganglia or periventricular hypodensities in three patients.
      CONCLUSIONS: In patients with macrocephaly at birth or rapidly developing within
      the first weeks of life, US should be performed as the primary imaging modality.
      Cyst-like bilateral widening of the sylvian fissures is the first sign of GA-I,
      followed by progressive fronto-temporal and ventricular enlargement. These
      patients should be screened for GA-I in order to initiate treatment in the
      asymptomatic stage.

PMID- 9933339
TI  - The role of the IAEA in nuclear medicine. International Atomic Energy Agency.

PMID- 9933340
TI  - A method to evaluate intra-operative gamma probes for sentinel lymph node
      localisation.
AB  - A method is described to allow objective evaluation of intra-operative gamma
      probe performance for the task of sentinel lymph node localisation. The method
      uses simple simulation based upon standard sensitivity and spatial resolution
      measurements at depth in water, with technetium-99m sources. The aim is to
      predict the minimum separation between the injection site and lymph node required
      to allow the sentinel lymph node to be identified in the presence of high
      injection site activity. The simulation methodology allows rapid investigation of
      probe performance for a range of node and injection site activities, and a range
      of node and injection site depths, without the need to perform a large number of
      physical measurements. Examples of practical performance simulations are given
      from five probes, showing that nodes at less than 115 mm from the injection site
      may be poorly localised, with even the best performing probe requiring at least
      51 mm separation to allow detection in the high background from the injection
      site. This method provides data to allow the ranking of probe system performance
      in terms of the practical task of sentinel lymph node localisation, rather than
      arbitrary ranking based upon basic physical performance measures such as spatial
      resolution and sensitivity. The best probes allow sentinel lymph node
      localisation at between 20 and 30 mm closer to the injection site than the
      poorest performing probes, for situations which represent intra-operative
      localisation in melanoma and breast surgery. The method is also shown to assist
      in optimising system settings such as energy detection thresholds, and may allow
      users to understand the limitations and capabilities of intra-operative gamma
      probes.

PMID- 9933341
TI  - Towards quality assurance of the sentinel node procedure in malignant melanoma
      patients: a single institution evaluation and a European survey.
AB  - The status of the regional lymph node (LN) is a critical component in staging
      patients with malignant melanoma. Biopsy of the first tumour-draining LN
      (sentinel node, SN) may replace routine elective LN dissection. However, until
      now, the applied methods have differed widely. Therefore, the aim of this study
      was to formulate recommendations for the pre-operative identification and intra
      operative retrieval of the SN. We present the results of an independent survey of
      the clinical practice of the SN procedure via a postal questionnaire among 136
      nuclear physicians in different institutes throughout 16 European countries.
      Moreover, the results of the SN procedure in our institution in an open
      prospective intervention trial in 80 patients with malignant melanoma without
      palpable LNs are also presented. In our protocol, on average, 6 h prior to
      surgery, 80 MBq technetium-99m nanocolloid was injected intracutaneously around
      the circumference of the diagnostic excision scar of the primary melanoma. No
      additional blue dye procedure was used to judge the accuracy of the radioguided
      SN procedure on its own. For successful identification of the radiolabelled SN,
      dynamic and static images were performed and the skin projection of the detected
      SN was marked with a cobalt-57 source. For intra-operative mapping a hand-held
      gamma probe was used. Forty of the 83 respondents of the European-wide
      questionnaire (48%) performed the SN procedure. Although many different regimens
      are used, the following recommendations could be deduced for the SN procedure in
      patients with malignant melanoma and non-palpable LNs: (1) local, intradermal
      injection of 40 MBq 99mTc-nanocolloid around the diagnostic excision scar of the
      primary melanoma; (2) two-phase LS: dynamic imaging (20 frames of 60 s, 128x128
      matrix, LEAP collimator) followed by static images 1-2 h later (180 s per
      record); (3) intra-operative retrieval of the SN with a gamma probe; (4)
      histopathological examination of the SN on serial sections. In our trial,
      surgical retrieval of the SN was successful in 95% of the cases. Dynamic
      lymphoscintigraphy (LS) contributed to the SN procedure by showing anatomically
      unpredictable lymph flow to extra-regional SNs (10% of the patients in this
      study) and multiple SNs. Of the 77 retrieved SNs, 13 contained metastatic disease
      (17%). Consequently, these patients underwent a formal LN dissection of the
      affected basin. In conclusion, the SN concept is a rational approach to select
      patients who could, theoretically, benefit from early LN dissection of the
      affected basin. Standardisation of the SN procedure will improve the results of
      this approach, and could be useful for quality control and for making comparisons
      with other countries in coming years.

PMID- 9933342
TI  - Technetium-99m HL91 uptake as a tumour hypoxia marker: relationship to tumour
      blood flow.
AB  - Technetium-99m HL91 (HL91) is a potential agent for imaging hypoxic tissue in
      vivo. To elucidate the relationship between hypoxia and blood flow in a tumour,
      dual-tracer autoradiography with HL91 and carbon-14 iodoantipyrine (IAP) was
      performed in a tumour-bearing rat model. The distribution of each tracer was
      analysed visually and semiquantitatively. In the tumours with central necrotic
      areas, HL91 uptake was marked around the necrotic areas whereas IAP uptake was
      marked at the periphery of the tumours, around the areas of marked HL91 uptake.
      Normalized HL91 uptake (%HL91) was highest in the low normalized IAP uptake
      (%IAP) fraction in the non-necrotic areas. There was a weak negative correlation
      between %HL91 and %IAP in the non-necrotic areas (r = -0.322, P<0.0001). In
      tumours with few or no necrotic areas, HL91 uptake was heterogeneous throughout
      the tumours, while IAP uptake predominantly occurred at the periphery of the
      tumours. %HL91 was higher in the inner two-thirds of the tumour than in the outer
      third. There was again a weak negative correlation between %HL91 and %IAP (r = 
      0.354, P<0.0001). This study confirmed that high HL91 uptake is related to low
      blood flow. The marked HL91 uptake around the necrotic region suggests the
      presence of chronic hypoxia in a tumour.

PMID- 9933343
TI  - Introducing fluorine-18 fluoromisonidazole positron emission tomography for the
      localisation and quantification of pig liver hypoxia.
AB  - Fluorine-18 labelled fluoromisonidazole ([18F]FMISO) has been shown to accumulate
      in hypoxic tissue in inverse proportion to tissue oxygenation. In order to
      evaluate the potential of [18F]FMISO as a possible positron emission tomography
      (PET) tracer for imaging of liver tissue hypoxia, we measured the [18F]FMISO
      uptake in 13 domestic pigs using dynamic PET scanning. Hypoxia was induced by
      segmental arterial hepatic occlusion. During the experimental procedure the
      fractional concentration of inspired oxygen (FiO2) was set to 0.67 in group A
      (n=6) and to 0.21 in group B (n=7) animals. Before and after arterial occlusion,
      the partial pressure of O2 in tissue (TPO2) and the arterial blood flow were
      determined in normal flow and flow-impaired liver segments. Standardised uptake
      values [SUV=kBq tissue (in g) / body weight (in kg) x injected dose (in kBq)] for
      [18F]FMISO were calculated from PET images obtained 3 hours after injection of
      about 10 MBq/kg body weight [18F]FMISO. Immediately before PET scanning, the mean
      arterial blood flow was significantly decreased in arterially occluded segments
      [group A: 0. 41 (0.32-0.52); group B: 0.24 (0.16-0.33) ml min-1 g-1] compared
      with normal flow segments [group A: 1.05 (0.76-1.46); group B: 1.14 (0.83-1.57)
      ml min-1 g-1; geometric mean (95% confidence limits); P<0.001 for both groups].
      After PET scanning, the TPO2 of occluded segments (group A: 5.1 (4.1-6.4); group
      B: 3.5 (2.6-4.9) mmHg] was significantly decreased compared with normal flow
      segments [group A: 26.4 (21.2-33.0); group B: 18.2 (13.3-25.1) mmHg; P<0.001 for
      both groups]. During the 3-h PET scan, the mean [18F]FMISO SUV determined in
      occluded segments increased significantly to 3.84 (3.12-4.72) in group A and 5.7
      (4.71-6.9) in group B, while the SUV remained unchanged in corresponding normal
      liver tissue [group A: 1.4 (1.14-1. 71); group B: 1.31 (1.09-1.57); P<0.001 for
      both groups]. Regardless of ventilation conditions, a significant inverse
      exponential relationship was found between the TPO2 and the [18F]FMISO SUV (r2=0.
      88, P<0.001). Our results suggest that because tracer delivery to hypoxic tissues
      was maintained by the portal circulation, the [18F]FMISO accumulation in the
      liver was found to be directly related to the severity of tissue hypoxia. Thus,
      [18F]FMISO PET allows in vivo quantification of pig liver hypoxia using simple
      SUV analysis as long as tracer delivery is not critically reduced.

PMID- 9933345
TI  - Are restrictions to behaviour of patients required following fluorine-18
      fluorodeoxyglucose positron emission tomographic studies?
AB  - The clinical use of positron emission tomography (PET) is expanding rapidly in
      most European countries. It is likely therefore that patients receiving the
      tracer fluorine-18 fluorodeoxyglucose (18FDG) will be discharged to come into
      contact with family members, members of the public and ward staff. There are few
      direct measurements on which to base any recommendations with regard to radiation
      protection, and so we have measured the dose rates from patients undergoing
      clinical PET examinations in our centre. Seventy-five patients who underwent
      whole-body and brain 18FDG PET examinations were studied. Dose rates were
      measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the
      department. The median administered activity was 323 MBq with a 95th percentile
      value of 360 MBq. The median dose rates measured at the four distances were 90.0,
      35.0, 14.0 and 5.0 microSv h-1 (the median dose rates per unit administered
      activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 microSv h-1 MBq-1).
      The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 microSv h
      1 (0.43, 0.2, 0.08 and 0.03 microSv h-1 MBq-1). A number of social situations
      were modelled and an annual dose limit of 1 mSv was used to determine whether
      restrictive behavioural advice was required. In the case of nursing staff on
      wards a value of 6 mSv was regarded as the annual limit, which translates to a
      daily limit of approximately 24 microSv. There is no need for restrictive advice
      for patients travelling by public or private transport when they leave the
      department 2 h after the administration of 18FDG. Similarly, there is no need for
      restrictive advice with regard to their contact with partners, work colleagues or
      children of any age, although it should be stressed that children should not
      accompany the patient to the scanning department. The only possible area of
      concern is in an oncology ward, where patients may be regularly referred for PET
      investigations and other high activity radionuclide studies and are partially
      helpless. Even in this area, however, it is unlikely that a nurse would receive a
      daily dose of more than 24 microSv. We conclude that there is no need for
      restrictive advice for patients undergoing 18FDG PET studies given the current
      administered activities.

PMID- 9933344
TI  - Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and
      pharmacokinetics in cancer patients.
AB  - A three-step avidin-biotin approach has been applied as a pretargeting system in
      radioimmunotherapy (RIT) as an alternative to conventional RIT with directly
      labelled monoclonal antibodies (MoAbs). Although dosimetric and toxicity studies
      following conventional RIT have been reported, these aspects have not previously
      been evaluated in a three-step RIT protocol. This report presents the results of
      pharmacokinetic and dosimetric studies performed in 24 patients with different
      tumours. Special consideration was given to the dose delivered to the red marrow
      and to the haematological toxicity. The possible additive dose to red marrow due
      to the release of unbound yttrium-90 was investigated. The protocol consisted in
      the injection of biotinylated MoAbs (first step) followed 1 day later by the
      combined administration of avidin and streptavidin (second step). After 24 h,
      biotin radiolabelled with 1.85-2.97 GBq/m2 of 90Y was injected (third step). Two
      different chelating agents, DTPA and DOTA, coupled to biotin, were used in these
      studies. Indium-111 biotin was used as a tracer of 90Y to follow the
      biodistribution during therapy. Serial blood samples and complete urine
      collection were obtained over 3 days. Whole-body and single-photon emission
      tomography images were acquired at 1, 16, 24 and 40 h after injection. The
      sequence of images was used to extrapolate 90Y-biotin time-activity curves.
      Numerical fitting and compartmental modelling were used to calculate the
      residence time values (tau) for critical organs and tumour, and results were
      compared; the absorbed doses were estimated using the MIRDOSE3.1 software. The
      residence times obtained by the numerical and compartmental models showed no
      relevant differences (<10%); the compartmental model seemed to be more
      appropriate, giving a more accurate representation of the exchange between
      organs. The mean value for the tau in blood was 2.0+/-1.1 h; the mean urinary
      excretion in the first 24 h was 82.5%+/-10.8%. Without considering any
      contribution of free 90Y, kidneys, liver, bladder and red marrow mean absorbed
      doses were 1.62+/-1.14, 0.27+/-0.23, 3.61+/-0.70 and 0. 11+/-0.05 mGy/MBq,
      respectively; the effective dose was 0.32+/-0.06 mSv/MBq, while the dose to the
      tumour ranged from 0.62 to 15.05 mGy/MBq. The amount of free 90Y released after
      the injection proved to be negligible in the case of 90Y-DOTA-biotin, but
      noteworthy in the case of 90Y-DTPA-biotin (mean value: 5.6%+/-2.5% of injected
      dose), giving an additive dose to red marrow of 0.18+/-0.08 mGy per MBq of
      injected 90Y-DTPA-biotin. Small fractions of free 90Y originating from incomplete
      radiolabelling can contribute significantly to the red marrow dose (3.26 mGy per
      MBq of free 90Y) and may explain some of the high levels of haematological
      toxicity observed. These results indicate that pretargeted three-step RIT allows
      the administraton of high 90Y activities capable of delivering a high dose to the
      tumour and sparing red marrow and other normal organs. Although 90Y-biotin clears
      rapidly from circulation, the use of DOTA-biotin conjugate for a stable chelation
      of 90Y is strongly recommended, considering that small amounts of free 90Y
      contribute significantly in increasing the red marrow dose.

PMID- 9933346
TI  - The role of FDG-PET, HMPAO-SPET and MRI in the detection of brain involvement in
      patients with systemic lupus erythematosus.
AB  - Involvement of the brain is one of the most important complications of systemic
      lupus erythematosus (SLE); however, its diagnosis is difficult due to the lack of
      effective imaging methods. We combined three brain imaging modalities - positron
      emission tomography with fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG-PET), single
      photon emission computed tomography with technetium-99m hexamethylpropylene amine
      oxime (HMPAO-SPET) and magnetic resonance imaging (MRI) - in order to detect
      brain involvement in SLE. Thirty-seven SLE patients, aged 22-45 years, were
      divided into three groups. Group 1 (G1) consisted of ten patients with major
      neuropsychiatric manifestations; group 2 (G2) consisted of 15 patients with minor
      manifestations; and group 3 (G3) consisted of 12 patients without manifestations.
      FDG-PET findings were abnormal in 51% of patients: 90% of G1, 67% of G2 and 0% of
      G3 patients respectively. HMPAO-SPET findings were abnormal in 62% of patients:
      100% of G1, 73% of G2 and 17% of G3 patients respectively. MRI findings were
      abnormal in 35% of patients: 70% of G1, 40% of G2 and 0% of G3 patients
      respectively. Grey matter was more commonly involved than white matter; 62% of
      patients presented with lesions in the cerebral cortex, 27% with lesions in the
      basal ganglion, 5% with lesions in the cerebellum, and 19% with lesions in white
      matter. No white matter lesions were found on FDG-PET or HMPAO-SPET. However, in
      19% of patients, MRI demonstrated abnormally high signal lesions in white matter.
      Forty-three percent of cases had positive serum anticardiolipin antibodies (ACA).
      However, ACA was not related to FDG-PET, HMPAO-SPET or MRI findings. It may be
      concluding that HMPAO-SPET is a more sensitive tool for detecting brain
      involvement in SLE patients when compared with FDG-PET or MRI. However, MRI is
      necessary for detecting lesions in white matter.

PMID- 9933347
TI  - Human cerebral acetylcholinesterase activity measured with positron emission
      tomography: procedure, normal values and effect of age.
AB  - The regional cerebral metabolic rate of [11C]N-methyl-4-piperidyl acetate, which
      is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity,
      was measured by dynamic positron emission tomography in 20 healthy subjects with
      a wide age range (24-89 years). Quantitative measurement was achieved using a
      kinetic model which consisted of arterial plasma and cerebral tissue
      compartments. The plasma input function was obtained using thin-layer
      chromatography and an imaging phosphor plate system at frequent sampling
      intervals to catch the rapid metabolism of the tracer in the blood. The
      distribution of the rate constant k3, an index of AChE activity, agreed well with
      reported post-mortem AChE distribution in the cerebral cortex (0.067-0.097 min-1)
      and thalamus (0.268 min-1), where AChE activity was low to moderate. The k3
      values in the striatum and cerebellum, where AChE activity was very high, did not
      respond linearly to AChE activity because of increased flow dependency. No
      significant effect of age was found on AChE activity of the cerebral cortex,
      suggesting that the ascending central cholinergic system is preserved in normal
      aging. This study has shown that quantitative measurement of enzyme activity in
      the living brain is possible through appropriate modelling of tracer kinetics and
      accurate measurement of the input function. The method should be applicable to
      patients with Alzheimer's disease and those with other kinds of dementia whose
      central cholinergic system has been reported to be disturbed.

PMID- 9933348
TI  - Evaluation of l-3-[123I]iodo-alpha-methyltyrosine SPET and
      [18F]fluorodeoxyglucose PET in the detection and grading of recurrences in
      patients pretreated for gliomas at follow-up: a comparative study with
      stereotactic biopsy.
AB  - Based on the results of stereotactic biopsy, we evaluated in a prospective
      fashion the efficiency of l-3-[123I]iodo-alpha-methyltyrosine-single-photon
      emission tomography (SPET) and [18F]fluorodeoxyglucose (FDG) positron emission
      tomography (PET) in the detection and grading of recurrences in patients
      previously treated for gliomas. The patient population comprised 30 individuals,
      nine with astrocytomas of grade II, ten with astrocytomas of grade IV, three with
      oligoastrocytomas of grade II, six with oligodendrogliomas of grade II and two
      with anaplastic oligodendrogliomas of grade III) suspected of recurrence and
      scheduled for further treatment. IMT SPET data were acquired using either by dual
      or a triple-headed SPET camera, Multispect 2/3. FDG uptake was measured with an
      ECAT ART PET camera. Two independent observers classified PET and SPET images as
      positive or negative for tumour tissue. Uptake of FDG and IMT was evaluated
      visually and, in the case of IMT, also quantitatively by calculating the ratios
      between tracer accumulation in the lesion and the unaffected contralateral
      regions of reference using the region of interest (ROI) technique. The PET and
      SPET results were compared with the histopathological findings obtained either by
      stereotactic biopsy or in one case by open surgery. Glucose metabolism and amino
      acid uptake of recurrences of brain tumours as assessed by FDG-PET and IMT-SPET
      correlated highly with the histopathological findings. Based on the
      histopathological data, FDG-PET and IMT-SPET findings confirmed recurrence in all
      cases of high-grade gliomas (IV). A difference could be demonstrated in low-grade
      (II-III) tumour recurrences. True-positive IMT-SPET results were found in 86% of
      grade III and 75% of grade II recurrences, whereas FDG-PET yielded a sensitivity
      of 71% in tumours of grade III and 50% in those of grade II. With respect to the
      grade of malignancy of brain tumours at recurrence, IMT-SPET, in contrast to FDG
      PET, does not permit adequate in vivo grading of non-mixed brain tumours of
      astrocytic or oligodendroglial origin. However, in this study FDG-PET did not
      permit discrimination between upgrading of low-grade oligoastrocytomas (II) into
      anaplastic oligodendrogliomas (III) and upgrading into glioblastomas (IV) The
      results of this study indicate that FDG-PET and IMT-SPET are equivalent to
      stereotactic biopsy in their ability to identify high-grade tumours at
      recurrence. IMT-SPET proved to be superior to FDG-PET in confirming low-grade
      recurrences. In the case of suspected progression of the grade of malignancy in
      ordinary gliomas, FDG-PET correlated significantly with the histopathological
      grading, whereas IMT-SPET did not. However, tumour grading by FDG-PET has a
      limitation in mixed brain tumours in that it is not possible to discriminate
      between progression of the oligo- versus the astrocytic tumour entity. In this
      case histopathological evaluation of the tumour grade remains necessary.

PMID- 9933349
TI  - Mercaptoacetyltriglycine diuretic renography and output efficiency measurement in
      renal transplant patients.
AB  - Suspected urinary tract obstruction following renal transplantation presents a
      diagnostic dilemma. The purposes of this study were: (1) to establish a normal
      range of measurement of output efficiency (OE) in the renal transplant
      population, and (2) to assess prospectively the usefulness of OE in the setting
      of allograft obstruction. Twenty-two renal transplant patients with stable renal
      function and no evidence of hydronephrosis on serial ultrasound examination had a
      diuretic mercaptoacetyltriglycine scan with calculation of OE. Three renal
      transplant patients with confirmed graft obstruction were also studied. Standard
      qualitative and quantitative parameters as well as OE were calculated. The mean
      OE for the 22 normal renal transplant patients was 86.3%+/-3.7% (range: 77%-91%).
      OE values in the three obstructed patients were 59%, 68% and 75% respectively. It
      is concluded that OE should normally exceed 77% in renal graft recipients. OE is
      a promising means of diagnosing functional obstruction in these patients.

PMID- 9933350
TI  - Assessment of various parameters in the estimation of differential renal function
      using technetium-99m mercaptoacetyltriglycine.
AB  - Differential renal function (DRF) is an important parameter that should be
      assessed from virtually every dynamic renogram. With the introduction of
      technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), a tracer with a high renal
      extraction, the estimation of DRF might hopefully become accurate and
      reproducible both between observers in the same institution and also between
      institutions. The aim of this study was to assess the effect of different
      parameters on the estimation of DRF. To this end we investigated two groups of
      children: group A, comprising 35 children with a single kidney (27 of whom had
      poor renal function), and group B, comprising 20 children with two kidneys and
      normal global function who also had an associated 99mTc-dimercaptosuccinic acid
      scan (99mTc-DMSA). The variables assessed for their effect on the estimation of
      DRF were: different operators, the choice of renal regions of interest (ROIs),
      the applied background subtraction, and six different techniques for analysis of
      the renogram. The six techniques were based on: linear regression of the slopes
      in the Rutland-Patlak plot, matrix deconvolution, differential method, integral
      method, linear regression of the slope of the renograms, and the area under the
      curve of the renogram. The estimation of DRF was less dependent upon both
      observer and method in patients with two normally functioning kidneys than in
      patients with a single kidney. The inter-observer comparison among children in
      either group was not dependent on either ROI or background subtraction. However,
      in patients with poor renal function the method of choice for the estimation of
      DRF was dependent on background subtraction, though not ROI. In children with two
      kidneys and normal renal function, the estimation of DRF from the 24 techniques
      gave similar results. Methods that produced DRF values closest to expected
      results, from either group of children, were the Rutland-Patlak plot and matrix
      deconvolution methods.

PMID- 9933351
TI  - Whole-body and pinhole bone scintigraphic manifestations of Reiter's syndrome:
      distribution patterns and early and characteristic signs.
AB  - The characteristic whole-body and pinhole scintigraphic manifestations of osteo
      enthesopathy and arthropathy in Reiter's syndrome (RS) are described, with an
      emphasis on early diagnosis. We analysed 59 sets of whole-body and pinhole bone
      scintigrams of 59 patients with RS. The population comprised 47 men and 12 women
      with an age range from 15 to 53 years (mean=29.4). Bone scintigraphy was carried
      out 2-2.5 h after intravenous injection of technetium-99m hydroxydiphosphonate
      using a single-head gamma camera (Siemens Orbiter Model 6601) with a low-energy
      high-resolution and a 4-mm pinhole collimator for whole-body and pinhole
      scintigraphy, respectively. In total 262 lesions of osteo-enthesopathy and
      arthritis were detected on 59 whole-body scintigrams, an incidence of 4.4 lesions
      per patient. As anticipated, the lesional distribution was asymmetrical: 68% were
      in the lower limb skeleton and 32% in the axial and upper limb skeleton. Pinhole
      bone scintigraphy, applied selectively to one region of interest in each case,
      enabled us to accurately diagnose arthritis and osteo-enthesopathy. It was
      noteworthy that osteo-enthesopathy, alone or in combination with arthritis,
      occurred in 78.9%, and had a strong predilection for the foot bones, especially
      the calcaneus (25. 6%). Pinhole scintigraphy detected enthesopathy in the absence
      of radiographic alteration in 14.1% of cases and portrayed characteristic signs
      of RS in 6.9%. Whole-body bone scintigraphy augmented with pinhole scintigraphy
      was found to be useful in order to panoramically display the systemic involvement
      pattern, to assess the characteristic bone and articular alterations and to
      detect early signs of RS.

PMID- 9933352
TI  - Imaging of the dopaminergic neurotransmission system using single-photon emission
      tomography and positron emission tomography in patients with parkinsonism.
AB  - Parkinsonism is a feature of a number of neurodegenerative diseases, including
      Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.
      The results of post-mortem studies point to dysfunction of the dopaminergic
      neurotransmitter system in patients with parkinsonism. Nowadays, by using single
      photon emission tomography (SPET) and positron emission tomography (PET) it is
      possible to visualise both the nigrostriatal dopaminergic neurons and the
      striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of
      elements of the dopaminergic system can play an important role in the diagnosis
      of several parkinsonian syndromes. This review concentrates on findings of SPET
      and PET studies of the dopaminergic neurotransmitter system in various
      parkinsonian syndromes.

PMID- 9933353
TI  - GRC5 and NMD3 function in translational control of gene expression and interact
      genetically.
AB  - The yeast gene, GRC5 (growth control), is a member of the highly conserved QM
      gene family, the human member of which has been associated with the suppression
      of Wilms' tumor. GRC5 encodes ribosomal protein L10, which is thought to play a
      regulatory role in the translational control of gene expression. A revertant
      screen identified four spontaneous revertants of the mutant grc5-1ts allele.
      Genetic and phenotypic analysis showed that these represent one gene, NMD3, and
      that the interaction of NMD3 and GRC5 is gene-specific. NMD3 was previously
      identified as a component of the nonsense-mediated mRNA decay pathway. The point
      mutations within NMD3 reported here may define a domain important for the
      functional interaction of Grc5p and Nmd3p.

PMID- 9933354
TI  - The influence of mutation rad57-1 on the fidelity of DNA double-strand gap repair
      in Saccharomyces cerevisiae.
AB  - The role of the RAD57 gene in double-strand gap (DSG) repair has been examined.
      The repair of a linearized plasmid, bearing a DSG, has been analyzed in a rad57-1
      mutant of Saccharomyces cerevisiae. For effective rejoining of the ends of
      plasmid DNA in the rad57 mutant the sequence of chromosomal DNA homologous to the
      DSG region is required. However, DSG repair (restoration of plasmid circularity)
      in rad57 cells is not accompanied by the recovery of DSGs. The DSG repair, which
      depends on an homologous chromosomal DNA sequence, requires the cohesive ends of
      DSGs. The non-cohesive-ended DSGs are repaired in rad57 cells by a pathway
      independent of the homologous recombination between chromosomal and plasmid DNA.
      We presume that the rad57-1 mutation is connected with the inhibition of DNA
      repair synthesis, required for filling the DSG. This situation produces a
      condition of "homology-dependent ligation", the alternative minor mechanism of
      recombinational DSG repair, that takes place in mutant cells. A molecular model
      for "homology-dependent ligation" in rad57 cells is proposed.

PMID- 9933355
TI  - YNT20, a bypass suppressor of yme1 yme2, encodes a putative 3'-5' exonuclease
      localized in mitochondria of Saccharomyces cerevisiae.
AB  - Mutation of YME genes in yeast results in a high rate of mitochondrial DNA escape
      to the nucleus. The synthetic respiratory growth defect of yme1 yme2 yeast
      strains is suppressed by recessive mutations in YNT20. Inactivation of YNT20
      creates a cold-sensitive respiratory growth defect that is more pronounced in a
      yme1 background and which is suppressed by yme2. Inactivation of YNT20 causes a
      qualitative reduction in the rate of mitochondrial DNA escape in yme1, but not
      yme2, strains, suggesting that YNT20 plays a role in the yme1-mediated
      mitochondrial DNA escape pathway. YNT20p is a soluble mitochondrial protein that
      belongs to a subfamily of putative 3'-5' exonucleases. Furthermore, conserved
      sequence elements in Yme2p suggest that this protein may also function as an
      exonuclease.

PMID- 9933356
TI  - In vivo mitochondrial DNA-protein interactions in sea urchin eggs and embryos.
AB  - Footprinting studies with the purine-modifying agent dimethyl sulphate were
      performed in Paracentrotus lividus eggs and embryos to analyze in vivo the
      interactions between protein and mitochondrial DNA. Footprinting in the small non
      coding region and at the boundary between the ND5 and ND6 genes revealed two
      strong contact sites corresponding with the in vitro binding sequences of
      mitochondrial D-loop-Binding Protein (mtDBP). The analysis of the pause region of
      mtDNA replication showed a strong footprint corresponding with the binding site
      of the mitochondrial Pause region-Binding Protein-2 (mtPBP-2), but only a very
      weak signal at the binding site of the mitochondrial Pause region-Binding Protein
      1 (mtPBP-1), which in vitro binds DNA with high efficiency. In vitro and in vivo
      analysis of the 3' end-region of the two rRNA genes showed no significant protein
      DNA interactions, suggesting that, in contrast to mammals, the 3' ends of sea
      urchin mitochondrial rRNAs are not generated by a protein-dependent transcription
      termination event. These and other data support a model in which expression of
      mitochondrial genes in sea urchins is regulated post-transcriptionally.
      Footprinting at the five AT-rich consensus regions allowed the detection of a
      binding site in the non-coding region for an as-yet unidentified protein, mtAT
      1BP. The occupancy of this site appears to be developmentally regulated, being
      detectable in the pluteus larval stage, but not in unfertilized eggs.

PMID- 9933357
TI  - Identification of DNA sequences controlling light- and chloroplast-dependent
      expression of the lhcb1 gene from Chlamydomonas reinhardtii.
AB  - In Chlamydomonas reinhardtii, expression of the lhcb1 gene encoding a chlorophyll
      a/b-binding protein of photosystem II is highly regulated by light, inhibitors of
      chlorophyll synthesis, as well as by circadian rhythms. In light/dark
      synchronized cultures, the rapid increase of lhcb1 mRNA levels during the light
      phase is regulated primarily at the transcriptional level. We have used the
      arylsulphatase (ars) reporter gene to analyze the lhcb1 5' upstream sequences for
      the presence of light-responsive elements. In transformants carrying chimeric
      reporter genes, accumulation of lhcb1/ars mRNA is markedly stimulated by light,
      with a time course similar to that of transcripts from the endogenous lhcb1 gene.
      Promoter deletion studies revealed that a 255-bp fragment of the lhcb1 5'
      upstream region is sufficient to confer proper light regulation on the
      promoterless ars gene. Moreover, the region between positions -255 and -122 with
      respect to the start site of translation were found to contain one or more light
      responsive elements. Strikingly, these sequences also seem to be involved in
      chloroplast-dependent lhcb1 gene expression as indicated by Northern analyses of
      transformants with photo-oxidatively damaged chloroplasts. This suggests that
      both light- and chloroplast-dependent expression of the lhcb1 gene are mediated
      by the same cis-acting elements.

PMID- 9933358
TI  - The Aspergillus nidulans gltA gene encoding glutamate synthase is required for
      ammonium assimilation in the absence of NADP-glutamate dehydrogenase.
AB  - Mutants of Aspergillus nidulans lacking NADP-glutamate dehydrogenase activity
      grow more poorly than wild-type strains on ammonium as a sole nitrogen source.
      The leaky growth of these mutants is indicative of an alternative pathway of
      ammonium assimilation and glutamate biosynthesis. We have PCR-amplified a portion
      of the A. nidulans gene encoding glutamate synthase and used this sequence to
      inactivate the genomic copy. This gene, designated gltA, was found to be
      dispensable for growth on ammonium in the presence of NADP-glutamate
      dehydrogenase activity. However, a strain carrying the gltA inactivation together
      with an NADP-glutamate dehydrogenase structural gene mutation (gdhA) was unable
      to grow on ammonium or on nitrogen sources metabolized via ammonium. The gltA
      gene was located to linkage group V of the A. nidulans genetic map.

PMID- 9933359
TI  - Cloning and expression of the cDNA encoding an alternative oxidase gene from
      Aspergillus niger WU-2223L.
AB  - A cDNA fragment encoding the mitochondrial alternative oxidase, the enzyme
      responsible for cyanide-insensitive and salicylhydroxamic acid (SHAM)-sensitive
      respiration, from the citric acid-producing fungus Aspergillus niger WU-2223L was
      cloned and expressed in Escherichia coli as a host strain. Synthetic primers were
      designed from the conserved nucleotide sequences of the alternative oxidase genes
      from higher plants and a yeast. The 210-bp DNA fragment was amplified by PCR with
      these primers using chromosomal DNA of WU-2223L as a template, and was employed
      to screen a cDNA library of A. niger. One full-length cDNA clone of 1.2 kb was
      obtained, and was sequenced to reveal that the clone contained an open reading
      frame (ORF-AOX1) encoding a polypeptide of 351 amino acids. The predicted amino
      acid sequence exhibited 50%, 55%, and 52% homology to the alternative oxidases of
      Hansenula anomala, Neurospora crassa and Sauromatum guttatum, respectively. In
      the 5'-terminus region of the ORF-AOX1, a mitochondrial targeting motif was
      found. The whole open reading frame of ORF-AOX1 was ligated to plasmid pKK223-3
      to construct the expression vector pKAOX1. The E. coli transformant harboring
      pKAOX1 showed cyanide-insensitive and SHAM-sensitive respiration, and expression
      was increased approximately two-fold by the addition of IPTG. These results
      indicated that the ORF-AOX1 encodes an alternative oxidase of A. niger.

PMID- 9933360
TI  - Functional characterization of SOR1, a gene required for resistance to
      photosensitizing toxins in the fungus Cercospora nicotianae.
AB  - The Cercospora nicotianae SOR1 gene is required for resistance to singlet oxygen
      generating photosensitizers. SOR1 was characterized in the wild-type and in five
      photosensitizer-sensitive mutant strains which are complemented to
      photosensitizer resistance by transformation with SOR1. Sequence analysis
      determined that three of the mutants contain SOR1 copies with mutations encoding
      substitutions in the protein-coding sequence; however, two other mutants had wild
      type SOR1 protein and promoter sequences. All five mutants accumulate SOR1 mRNA
      at levels comparable to that of the wild-type strain. In the wild-type strain,
      SOR1 accumulation is enhanced two-fold by light, but is unaffected by the
      presence of cercosporin, the photosensitizer synthesized by C. nicotianae.
      Southern analysis indicates that SOR1 is present in other fungi that synthesize
      structurally related perylenequinone photosensitizers.

PMID- 9933361
TI  - Identification of incompatibility alleles and characterisation of molecular
      markers genetically linked to the A incompatibility locus in the white rot fungus
      Pleurotus ostreatus.
AB  - Pleurotus ostreatus is a hetertothallic homobasidiomycete whose mating is
      controlled by a bifactorial tetrapolar genetic system. Although this mechanism is
      well accepted, there is a lack of knowledge about its molecular basis, as the
      incompatibility loci have not been cloned and sequenced. As a first step towards
      the elucidation of the molecular structure of the A-type incompatibility locus,
      molecular markers have been isolated which correspond to genomic sequences
      present in different strains of P. ostreatus but not in other higher
      basidiomycetae. These markers reveal single-copy genetic regions in which some
      degree of genetic variability can be detected.

PMID- 9933362
TI  - Teleneuropathology: a means to improve the correctness of neuropathological
      diagnoses in clinical practice.
AB  - Telepathology in general, and teleneuropathology in particular is the practice of
      pathology at a distance, viewing digitized images of histological slides on a
      video monitor rather than directly through a light microscope. For the
      transmission of the digitized images from a telemicroscope to the remote
      diagnostic video monitor, different technologies such as ordinary telephone
      lines, broadband telecommunications channels, and even the Internet can be used.
      The transmitted images may serve for primary neuropathological diagnosis,
      teleconsultation, quality assurance, proficiency testing, and distance learning.
      Static imaging and dynamic imaging are the two major competing technologies of
      telemicroscopy. Static-imaging systems appear to have levels of diagnostic
      accuracy that are not satisfactory for diagnostic neuropathology. In contrast,
      high levels of diagnostic accuracy can be achieved using dynamic-imaging systems
      with the transmission of live video images in real time and by using a robotized
      telemicroscope under the control of the remote teleneuropathologist with the
      possibility to examine the entire histological specimen.

PMID- 9933363
TI  - Pathology of the peripheral nervous system.
AB  - In this review, the first four papers deal with an important chapter in
      peripheral nerve surgery: cranial nerve reconstruction after injury occurring
      during skull base surgery. The last paper discusses the problem of peripheral
      nerves affected by a ganglion cyst. Damage to a cranial nerve is no longer
      considered to be an absolutely irreparable event. The first two studies are
      related to facial nerve management during the surgical treatment of vestibular
      schwannomas. The most common mechanisms responsible for facial nerve injury
      during tumor removal and the technical means to avoid them are cited. The
      importance of intraoperative neurophysiologic monitoring to save the facial nerve
      is stressed. A comparison between microsurgery and radiosurgery results in the
      conclusion that for vestibular schwannomas, the first choice of treatment is
      microsurgery. These two large and exceptional series show that by using a refined
      technique it is possible to obtain both total tumor removal and preservation of
      the facial nerve in most of the vestibular schwannomas. In the minority of
      patients in whom the facial nerve is severed, there are several therapeutic
      options to re-establish facial nerve function. After facial nerve reconstruction,
      performed immediately during the same tumor operation, a satisfactory
      reinnervation was obtained in 74% of the cases. After facial nerve reanimation,
      using as donor nerve the hypoglossus and performed 1 week after the tumor
      operation, a satisfactory reinnervation was obtained in 96% of the cases. The
      other two papers deal with the intraoperative transection of the trochlear and
      abducens nerve during surgery for skull base tumors. These two cranial nerves,
      owing to their simply organized motor nerve system (they are purely motor nerves
      and supply one muscle each), show quite a good expectation of functional
      recovery. The behavior of ganglion cysts involving peripheral nerves is the topic
      of the last paper reviewed. These cysts are benign lesions that can cause
      permanent neurologic deficits of the involved nerve. The etiology, clinical
      presentation, surgical techniques, and recurrence rate are reported. In the
      present series, the outcomes after ganglion cyst excision are not as favorable as
      those reported in other series. Before surgery, patients must be informed about
      the possibility of residual motor deficits and recurrences.

PMID- 9933364
TI  - Cerebrospinal fluid spinal lumbar drainage: indications, technical tips, and
      pitfalls.
AB  - Since the publication by F. Vourc'h in 1963 [Br J Anaesth (1963) 35:118-120]
      describing the use of a plastic catheter inserted percutaneously for the drainage
      of lumbar cerebrospinal fluid (CSF) the indications for spinal drainage are
      numerous, but not very well systematized. The bibliographical review shows few
      recent papers concerning the techniques, indications, complications and pitfalls.
      The authors considered it interesting to analyze nine papers, in particular those
      dedicated to the use of spinal drainage in skull base surgery and in the
      prevention and/or treatment of CSF fistulas. Two papers describe for the first
      time pachymeningeal gadolinium enhancement associated with orthostatic headaches,
      owing to CSF hypotension mimicking an inflammatory or infiltrative disease. The
      results of the treatment of CSF fistulas are good with a high success rate,
      avoiding direct surgical repair. The use of a specially designed subarachnoid
      catheter is clearly superior to the epidural catheter, with good flow of CSF and
      minimal complications. The main problems are deficient flow and infections.
      Overdrainage is potentially dangerous, with acute pneumocephalus, brain collapse
      and neurological deterioration. Infrequent but possible is Chiari II-like
      syndrome with vocal cord paralysis and life-threatening aspiration, or temporal
      downward herniation with kinking of the posterior cerebral artery and acute brain
      infarct. The key to success lies in a rigid protocol, intermittent CSF drainage
      with a closed circuit, and daily biochemical and microbiological monitoring.
      Highly qualified medical and nursing staff are essential.

PMID- 9933365
TI  - Current applications of laser Doppler in the neurosurgical intensive care unit.
AB  - The invasive monitoring of the microcirculatory cerebral blood flow by laser
      Doppler flowmetry has been proposed as means for the detection and prevention of
      cerebral ischemia in comatose patients. However, the use of this technique is not
      widespread, nor has it proven to influence the patient's outcome. Recent reports
      selected from the literature are reviewed in order to define the indications,
      usefulness, limitations, and potential complications of the available methodology
      for the clinical monitoring of cerebral blood flow in neurosurgical patients by
      laser Doppler flowmetry.

PMID- 9933366
TI  - Management of deep-seated gliomas.
AB  - The management of thalamic and brain stem astrocytomas remains controversial.
      Treatment options are: (a) clinical observation, (b) radiotherapy without biopsy,
      (c) stereotactic biopsy followed by radio and/or chemotherapy, and (d) surgical
      removal with or without adjuvant therapy. Stereotactic surgical techniques have
      improved the morbidity and mortality rates of biopsies and surgical resection of
      deep-seated gliomas. The biologic behavior of these lesions is not well known and
      proliferation cell index tests may help in the choice of therapy. In this review,
      seven recent papers on the management of deep-seated gliomas are presented.
      Radical removal of thalamic pilocytic astrocytoma may cure the patient. In cases
      of low-grade astrocytomas, stereotactic guided surgical removal has low
      morbidity. Adjuvant radiotherapy should be used only in selected cases.
      Sterotactic biopsy followed by radio- and/or chemotherapy is the best option for
      thalamic or brain stem anaplastic astrocytomas and glioblastomas.

PMID- 9933367
TI  - Radiosurgery.
AB  - This review looks at papers dealing with radiosurgery for tumors, cavernous
      malformations, and arteriovenous malformations. The tumors were meningiomas, many
      of them at the base of the brain, and the results were excellent. One paper used
      the gamma knife for patients with cavernous malformations. The authors
      encountered significant morbidity and concluded that these lesions should be
      treated surgically. There are two papers dealing with arteriovenous
      malformations. One of these showed that a significant number of arteriovenous
      malformations were not obliterated. The second report was on arteriovenous
      malformations treated with radiosurgery, and the authors found that some of the
      patients developed hemiparkinsonism and hemiparesis.

PMID- 9933368
TI  - Experimental animal models of traumatic brain injury: medical and biomechanical
      mechanism.
AB  - The numerous traumatic brain injury models were designed to study the nature of
      the human brain injury. The properties of six experimental injury models were
      reviewed in this article. Weight-drop models with or without skull protection
      were compared in terms of experimental setup, possible error source, and
      biomechanical prospect. The modified percussion models with or without rigid
      cortical impact were contrasted with regard to reliability, histopathological
      production, and deformation. The focal contusion model by mechanical suction
      force represented isolated cortical injury without compression brain injury. As a
      class of traumatic brain injury, brain retraction damage was reviewed in this
      article.

PMID- 9933370
TI  - Papers reviewed in this issue.

PMID- 9933371
TI  - Publications scanned for pertinent articles.

PMID- 9933372
TI  - Film reading session, ECR'99, Vienna.Moderator: christian J. Herold, M.D.,
      vienna, austria 

PMID- 9933373
TI  - MR imaging and CT of the female pelvis: radiologic-pathologic correlation.
AB  - For imaging of the female pelvis, transvaginal ultrasound is the method of
      choice. Magnetic resonance imaging and CT provide important additional
      information in various disorders. Magnetic resonance imaging is superior to CT in
      diagnosing benign and malignant disorders of the uterus. The same holds for the
      characterization of adnexal masses, where MR imaging reliably differentiates
      dermoids, ovarian fibromas, and most endometriomas. Differentiation of other
      benign and malignant ovarian tumors by CT and MR imaging is based on identical
      morphological criteria; no superiority of MR imaging over CT has been
      established. Computed tomography is still the preferred imaging modality for
      staging ovarian cancer. A thorough knowledge of the pathomorphological changes
      associated with the different disorders of the female pelvis not only helps to
      choose the proper imaging modality and examination protocol, but also improves
      image interpretation.

PMID- 9933374
TI  - CT and MRI of the male genital tract: radiologic-pathologic correlation.
AB  - Technical advances in magnetic resonance imaging (MRI), notably in high
      resolution MRI, have opened up new diagnostic applications in male pelvic
      pathology. A major indication is the preoperative staging of prostate cancer,
      where MRI is more reliable than other imaging modalities in differentiating
      between localized and advanced disease. In monitoring local recurrence after
      radical prostatectomy MRI is also valuable in differentiating scar tissue from
      new growth. In benign prostate disease, MRI effectively displays the congenital
      cysts that may be associated with infertility. Other disease, however - notably
      benign prostatic hyperplasia - is generally an incidental finding. Ultrasound
      remains the imaging modality of choice for evaluation of pathologies of the
      penis, testis and scrotum, e. g. in differentiating malignant from benign scrotal
      masses or in diagnosing acute scrotum due to testicular torsion or rupture. In
      isolated cases, MRI is also a valuable diagnostic aid in conditions of these
      organs, e. g. in the preoperative localization of ectopic testes in
      cryptorchidism or if US findings are equivocal.

PMID- 9933375
TI  - MRI with an endorectal coil for staging of clinically localised prostate cancer
      prior to radical prostatectomy.
AB  - The purpose of this study was to evaluate the ability of MR imaging with an
      endorectal coil (erMRI) to predict the local pathological stage of prostatic
      carcinoma prior to radical prostatectomy. Thirty-one consecutive patients (median
      age 61 years, range 40-71 years) with clinically localised prostate cancer were
      assessed preoperatively by endorectal MRI (at 1.0 T). The pulse sequences
      consisted of fast spin-echo axial and coronal T2-weighted images and inversion
      recovery with two echoes for axial fat-suppressed images. The assessment of
      tumour stage and measurement of tumour dimension by erMRI were compared with the
      corresponding findings on whole-mount step sections of the surgical specimens.
      Postoperatively, 14 of the 31 patients (45 %) were found to have extracapsular
      extension, 7 with capsular penetration (CP) only, and 7 had a combination of CP
      and seminal vesicle invasion (SVI). Capsular penetration was detected by erMRI
      with a sensitivity of 0.71 and specificity of 0.47, whereas the sensitivity for
      SVI detection was 0.71 and the specificity 0.83. Endorectal MRI for staging
      clinically localised prostatic carcinoma gives a good prediction of invasion of
      the seminal vesicles but is unreliable in predicting capsular penetration.

PMID- 9933376
TI  - Venous incompetence in erectile dysfunction: evaluation with color-coded duplex
      sonography and cavernosometry/-graphy.
AB  - The purpose of this study was to assess the accuracy of multi-parameter
      measurements with color-coded duplex sonography (CCDS) for the diagnosis of
      venous leakage in patients with erectile dysfunction. Sixty patients with
      repeated unsatisfactory reactions after intracavernous injection of vasoactive
      substances underwent CCDS. Following intracavernous injection of prostaglandin
      E1, peak systolic velocity (PSV), enddiastolic velocity (EDV), time averaged
      velocity (TAV), resistance index (RI), and pulsatility index (PI) were measured
      in the cavernous arteries over 30 min (one measurement per minute). The results
      were compared with independent measurements based on dynamic pharmaco
      cavernosometry/cavernosography (DPCC). Dynamic pharmaco
      cavernosometry/cavernosography revealed venous leakage in 33 patients. Of 48
      patients with normal PSV ( > 25 cm/s), 25 had veno-occlusive dysfunction and the
      remainder presented normal venous function. No statistically significant
      differences between these groups were found in EDV, RI, and PI measurements. In
      contrast, differences in TAV were significant between patients with (mean 9.4 +/-
      4.6 cm/s) and without venous leakage (mean 5.5 +/- 2.2 cm/s; p = 0.001). Analysis
      of relative frequencies revealed a broad overlap of EDV, TAV, RI, and PI
      measurements between both groups. Sensitivities and specificities determined from
      receiver-operating-characteristic curves were > 80 % and > 50% for a TAV
      threshold of 5 cm/s, and an RI threshold of 1.0. Measurements of EDV, TAV, RI,
      and PI in patients with repeated unsatisfactory reactions on intracavernous
      prostaglandin injection are poor predictors of venous leakage and should not
      replace DPCC in the investigation of vasculogenic impotence.

PMID- 9933377
TI  - Hamartoma of the urinary bladder: case report and review of the literature.
AB  - Bladder hamartoma is a rare benign entity with only eight cases reported in the
      literature thus far, and whose general imaging features have not, to our
      knowledge, been previously discussed. The purpose of this report is to review the
      literature and to discuss the imaging findings in one case of bladder hamartoma
      where US features were those of an inhomogeneous solid mass with an unechogenic
      center, which was in accordance with the CT findings of a soft tissue mass with
      central inhomogeneous enhancement due to central necrosis.

PMID- 9933378
TI  - Accessory cardiac bronchus: 3D CT demonstration in nine cases.
AB  - Accessory cardiac bronchus (ACB) has been described mainly as isolated case
      reports in the literature. We report nine consecutive cases of ACB, which
      occurred in five males and four females and were detected in 11,159 routine
      spiral CT examinations of the chest, performed between 1994 and 1998. Frequency
      of the anomaly was 0.08 %. Accessory cardiac bronchus originated from the
      intermediate bronchus in eight cases and from the right main bronchus in one
      case. Mean largest diameter of ACB was 8.7 mm (range 4.0-13.8 mm) and mean length
      was 11.9 mm (range 4.2-23.4 mm). An abnormal pulmonary artery was observed in one
      case. Six bronchi presented with a blind distal extremity and three showed a
      ventilated lobulus with a mean largest diameter of 37.5 mm (range 18.6-62.0 mm).
      All ACBs were documented by 3D shaded-surface display (SSD) and virtual
      endobronchial navigation, which may facilitate the diagnosis. The literature was
      reviewed.

PMID- 9933379
TI  - Pulmonary lymphangioleiomyomatosis: high-resolution CT findings.
AB  - Lymphangioleiomyomatosis (LAM) of the lung is a very rare disease. There are
      obvious discrepancies in the literature concerning the appearance of LAM on CT
      scans of the lung. This study adds the imaging findings of 11 patients and
      demonstrates how the imaging findings changed over time in four patients. Twenty
      two CT examinations, and radiographs that had been obtained close to the CT
      examinations, of 11 patients with LAM confirmed by open lung biopsy were
      retrospectively evaluated with particular attention to the size of cystic lesions
      and wall thickness. Furthermore the CT scans were analysed for the type of
      pulmonary infiltration process and its distribution, presence or absence of
      pleural effusion, pneumothorax and lymph node enlargement. Clinical and CT follow
      up studies were available in four patients. The CT scans revealed an increase in
      the interstitial pattern in all patients. Architectural distortion was seen in
      two patients and cystic lesions were present in all. The size of the cysts varied
      from small lesions to bullous emphysema. The cystic lesions revealed a wall
      thickness up to 2 mm but a wall was not perceptible in all. Pneumothorax was seen
      in only two patients; pleural effusion was seen in two patients. CT examination
      of patients with LAM reveals neither a uniform nor a pathognomonic appearance. In
      the early stages of LAM or in cases with interstitial changes the differential
      diagnosis of centrilobular emphysema or idiopathic pulmonary fibrosis seems to be
      more difficult than most authors believe.

PMID- 9933380
TI  - Radiolucencies and cavitation in bronchioloalveolar carcinoma: CT-pathologic
      correlation.
AB  - Bronchioloalveolar carcinoma (BAC) is a polymorphic lung cancer the incidence of
      which is rising. The presence of intratumoral radiolucencies is an important
      feature of bronchioloalveolar carcinoma. The aim of this study was to present
      pictorially the spectrum of intratumoral radiolucencies visible in BAC. In 57
      BACs studied with thin-slice CT, we identified six types of radiolucencies: (a)
      patent intratumoral bronchioles (air bronchiologram); (b) pseudocavitations; (c)
      cavitation; (d) serpentine radiolucencies; (e) internal alveologram; and (f)
      multiple cystic lesions.

PMID- 9933381
TI  - Intrathoracic rib demonstrated by helical CT with three-dimensional
      reconstruction.
AB  - Intrathoracic rib is a rare congenital anomaly. An unusual location with atypical
      pleural tenting is reported. Helical CT with three-dimensional reconstruction
      seems the best modality for demonstrating the origin and location of these
      abnormal ribs. The importance of the diagnosis of intrathoracic rib is to rule
      out pulmonary lesions and prevent unnecessary investigations.

PMID- 9933382
TI  - The pseudocapsule in hepatocellular carcinoma: correlation between dynamic MR
      imaging and pathology.
AB  - Nodular hepatocellular carcinoma (HCC) is characterized by the presence of a
      pseudocapsule (constructed usually from connective fibrous tissue) that appears
      hypointense on T1- and T2-weighted spin-echo (SE) and gradient-echo (GE) MR
      imaging sequences without a contrast medium. The presence of vascular structures
      inside the tumor, which are verified by histological exam, affects enhancement of
      the PC after administrating the contrast medium: The impregnation is more evident
      in the dynamic study but also persists on the delayed T1-weighted SE images. The
      accuracy of MR in detecting the pseudocapsule of HCC and contrast enhancement of
      the pseudocapsule during dynamic studies were evaluated and related to
      pathological findings. Thirty-seven HCC were examined in 33 patients and
      afterwards resected. In capsulated nodules, besides usual hematoxylin, eosin, and
      trichrome stainings, histochemical and immunohistochemical methods were
      performed. On a 1.5-T MR unit, T1- and T2-weighted SE and GE FLASH 2D sequences
      after intravenous injection of Gd-DTPA (dynamic study) were used. In a later
      phase, T1-weighted SE sequences were repeated. Histologically, the pseudocapsule
      (thickness 0.2-6 mm) was present in 26 of 37 nodules (70%). The dynamic study was
      the most suitable technique to show the pseudocapsule, which was recognized in
      80.7% (21 of 26 nodules). In 5 of 26 cases, the pseudocapsule, not demonstrated
      by MR, was thinner than 0.4 mm. In 16 of 21 cases, in the early portal phase (30
      60 s), the pseudocapsule had an early enhancement, which was more evident later;
      in 5 of 21 cases the enhancement was observed only in the late portal phase (1-2
      min). At histological examination, 14 of 16 pseudocapsules with early enhancement
      showed a more prominent vasculature than those with enhancement in the
      equilibrium phase. Magnetic resonance was a reliable tool in demonstrating the
      pseudocapsule of HCC. The histological examination demonstrated a good
      correlation between the enhancement behavior and the vessel number of the
      pseudocapsule.

PMID- 9933383
TI  - Assessment of gastric cancer: value of breathhold technique and two-phase spiral
      CT.
AB  - The purpose of this study was to evaluate the capabilities of subsecond spiral CT
      in detecting and staging of gastric cancer. Our study included 40 patients with
      endoscopically detected gastric carcinomas. Two-phase spiral CT was performed
      within one breathhold each. Distension of the stomach was achieved by intravenous
      application of scopolamine and drinking of 500 ml water. After bolus injection of
      contrast medium, scanning was performed in the arterial and venous phase. Gastric
      tumour extention and lymph node involvement was assessed. Gastric cancer was
      detected in 39 of 40 cases (sensitivity 97.5%). Location of the tumour was
      correctly assessed in all cases. In 31 of the 39 cases (79.4%) CT staging was
      accordant with pathological staging. One hundred two (70%) of 145 nodes
      infiltrated by tumour tissue were detected and 144 (42.8%) of 336 nodes free of
      metastatic involvement were found. The predictive values of positive and negative
      results for the detection of lymph node metastases were 67.1 and 75%,
      respectively. Spiral CT is recommended for staging of gastric cancer.

PMID- 9933384
TI  - 3D MR gastrography: exoscopic and endoscopic analysis of the stomach.
AB  - The aim of this study was to evaluate the feasibility of MR gastrography, based
      on 3D MRI following the oral administration of Gd-DOTA-enriched blueberry juice,
      in order to depict alterations of the gastric wall. The stomachs of three
      volunteers and three patients were examined on a 1.5-T MR system. Following
      ingestion of 400 ml of blueberry juice spiked with 2 ml of Gd-DOTA, each subject
      underwent 3D MR imaging in three positions: 45 degrees left lateral decubitus,
      supine, and 45 degrees right lateral decubitus. In each position, a coronal 3D
      SPGR acquisition consisting of 60 continuous 2-mm slices was acquired over a 35-s
      breathhold (TR/TE = 4.0/1.8 ms, 40 degrees flip angle, 0.5 excitations, voxel
      size of 1.25 x 1.66 x 2.00 mm). Multiplanar reformats (MPR), maximum intensity
      projections (MIP), surface shaded displays (SSD), and virtual intraluminal
      endoscopic views (VIE) were calculated. Magnetic resonance gastroscopy was
      tolerated well by all subjects without adverse effects. Based on the 3D MRI data
      sets acquired in various patient positions, all regions of the stomach and the
      proximal duodenum were visualized to good advantage. Whereas MPR and MIP provided
      a morphologic overview, SSD and VIE images permitted analysis of the gastric
      mucosa. Normal mucosa could be differentiated from the course and irregular
      pattern characterizing carcinomatous infiltration. The 3D SPGR data sets acquired
      following ingestion of oral Gd-DOTA-spiked blueberry juice permits exoscopic and
      virtual endoscopic viewing of the stomach.

PMID- 9933385
TI  - Evaluation of spiral CT in staging of colon and rectum carcinoma.
AB  - The purpose of our study was to evaluate the capability of a subsecond spiral-CT
      scanner using two contrast medium phases in staging of colorectal cancer. In our
      study we included 37 patients with proven rectum or colon carcinoma. Spiral CT
      was performed following tap-water enema of the colon in the arterial and venous
      phases of contrast medium enhancement. Our results were compared with the
      findings of pathological examination after surgery. The tumor's size and
      extension were evaluated in the arterial and venous phases, the lymph nodes in
      the venous phase of the CT scan. The tumor was in the rectum (n = 14), sigma (n =
      11), descending colon (n = 6), and cecum (n = 6). Two-phase spiral CT had a
      sensitivity of 97.2% in the arterial phase and 89.1% in the venous phase in
      detecting the carcinoma. The staging results were in the arterial phase in 30 of
      37 cases (81.0%) and in the venous phase in 24 of 37 cases (64.8%) according to
      pathology. In 27 of 32 patients (84.3%) lymph nodes were detected. The correct
      classification of the N-stage was possible in 23 of 34 cases (67.6%). The
      combined use of arterial and venous phases in staging of colorectal cancer can
      improve the T- and N-stage classification in comparison with using only one
      contrast medium phase. The arterial phase is superior compared with the venous
      phase for local tumor staging and the venous phase is used for lymph node
      assessment.

PMID- 9933386
TI  - Non-operative management of arterial liver hemorrhages.
AB  - A retrospective evaluation of embolotherapy in patients with arterial liver
      hemorrhages was carried out. Twenty-six patients, ranging in age from 10 days to
      77 years with active arterial liver hemorrhages, underwent non-surgical
      embolotherapy. Bleeding was attributed to trauma (n = 21), tumor (n = 3),
      pancreatitis (n = 1), or unknown cause (n = 1). Twenty-nine embolizations were
      performed via a transfemoral (n = 26) or biliary (n = 2) approach. One bare
      Wallstent was placed into the common hepatic artery via to an axillary route to
      cover a false aneurysm due to pancreatitis. Treatment was controlled in 4
      patients by cholangioscopy (n = 2) or by intravascular ultrasound (n = 2). Prior
      surgery had failed in 3 patients. Intervention controlled the hemorrhage in 24 of
      26 (92%) patients within 24 h. Embolotherapy failed in 1 patient with pancreatic
      carcinoma and occlusion of the portal vein. In 1 patient with an aneurysm of the
      hepatic artery treated by Wallstent insertion, total occlusion was not achieved
      in the following days, as demonstrated by CT and angiography. However, colour
      Doppler flow examination showed no flow in the aneurysm 6 months later.
      Complications were one liver abscess, treated successfully by percutaneous
      drainage for 10 days, and one gallbladder necrosis after superselective
      embolization of the cystic artery. Embolization is a effective tool with a low
      complication rate in the treatment of liver artery hemorrhage, even in patients
      in whom surgery has failed.

PMID- 9933387
TI  - Septic thrombosis of the portal vein due to peripancreatic ligamental abscess.
AB  - Septic thrombus formation of both the main portal vein and its intrahepatic
      branches were observed on CT in a patient with peripancreatic abscess. The septic
      thrombosis of portal vein (STPV) extended from the level of porta hepatis into
      the intrahepatic branches, but the portal vein and superior mesenteric vein at
      the level of pancreatic head were preserved with no evidence of thrombosis
      angiographically. The gas-containing abscess near the head of the pancreas
      extended toward the hepatic hilum and surrounded the portal vein and its branches
      on CT. It was concluded that these thrombi of portal vein branches at porta
      hepatis and intrahepatic branches were caused by extensions of peripancreatic
      abscess via the hepatoduodenal ligament and ligamentum teres. Computed tomography
      was useful in depicting the ligamentous spread of peripancreatic abscess
      resulting in STPV.

PMID- 9933388
TI  - Radiological findings of intraparenchymal liver Ascaris (hepatobiliary
      ascariasis).
AB  - Ascariasis is a well-known cause of acute cholangitis and cholecystitis; however,
      very rarely do worms penetrate and colonize the liver parenchyma. Here we present
      the unique radiological demonstration (US, CT and ERCP) of hepatobiliary
      ascariasis in which worm was first alive in the parenchyma of the liver and
      subsequently died and formed liver abscess.

PMID- 9933389
TI  - Imaging findings in Langerhans' cell histiocytosis of the liver and the spleen in
      an adult.
AB  - We present a case of Langerhans' cell histiocytosis (LCH) of the liver and spleen
      in an adult. The imaging features are different from those in the few previously
      reported cases of individual organ involvement by LCH.

PMID- 9933390
TI  - Three-dimensional cholangio-spiral CT demonstration of a post-traumatic bile leak
      in a child.
AB  - Bilioma is a rare complication of traumatic liver injury, and the precise site of
      bile leak is often difficult to demonstrate with a non-invasive technique. We
      report a case of post-traumatic bile leak in a 15-year-old girl in whom spiral CT
      after intravenous cholangiography allowed excellent preoperative demonstration of
      the extent of the liver rupture and an exact location of the bile leak. We think
      that spiral-CT cholangiography could be an accurate, non-invasive technique to
      investigate the biliary system in cases of paediatric liver trauma.

PMID- 9933391
TI  - Acromesomelic dysplasia associated with mild lumbar spine stenosis.
AB  - A rare case of acromesomelic dysplasia is reported. The radiological findings
      were consistent with shortness of all tubular bones, especially those of the
      forearms. There was also evidence of mild lumbar spine stenosis.

PMID- 9933392
TI  - Evaluation of the carotid and vertebral arteries: comparison of 3D SCTA and IA
      DSA-work in progress.
AB  - OBJECTIVE: The purpose of this study was to develop a method for three
      dimensional (3D) visualization of the whole vascular system of the carotid and
      vertebral arteries using spiral computed tomographic angiography (SCTA), that
      allows accurate, qualitative and quantitative evaluation, of anatomical
      abnormalities, including detection of additional lesions, and estimation of
      degree of stenosis. MATERIALS AND METHODS: Fifteen patients with anatomical and
      pathological abnormalities of the arterial vascular system detected by color
      coded duplex ultrasound were studied using intraarterial digital subtraction
      angiography (IA-DSA) with aortic arch injection, and SCTA. The carotid and
      vertebral arteries were segmented using an interactive threshold interval density
      volume-growing method and visualized with a color-coded shaded-surface display
      (SSD) rendering method. The adjacent bone structures were visualized using a
      transparent volume rendering method. RESULTS: In all cases, the entire volume of
      the vascular system of the carotid and vertebral arteries could be visualized on
      SCTA, and the anatomical and pathological abnormalities on 3D SCTA correlated
      well with that seen on IA-DSA. CONCLUSION: Results of 3D SCTA had a high degree
      of correlation with results of IA-DSA in the evaluation of the vascular system of
      the carotid and vertebral arteries. The 3D SCTA with a subsecond spiral CT
      scanner is useful for the visualization of anatomical and pathological
      abnormalities in the circulation in the carotid and vertebral arteries and offer
      a promising minimally invasive alternative compared with other diagnostic
      procedures.

PMID- 9933393
TI  - Sciatica caused by a dilated epidural vein: MR findings.
AB  - We report the MR imaging findings in a 41-year-old woman presenting with sudden
      low back pain and sciatica. At surgery a dilated epidural vein was found
      compressing the nerve root. The MR findings may suggest the diagnosis. Magnetic
      resonance imaging of a dilated epidural vein or varix causing sciatica has not
      been reported until now.

PMID- 9933394
TI  - Amplitude-coded color doppler: clinical applications.
AB  - Amplitude-coded color Doppler sonography (ACD) has become an useful adjunct to
      gray-scale US and conventional color Doppler sonography (CD) for the assessment
      of vascular diseases and pathologic conditions that might affect or alter tissue
      vascularization or perfusion. Basically, all US units that generate conventional
      color Doppler information through autocorrelation technique are capable of
      displaying ACD. This technique is also referred to as power Doppler, amplitude
      mode color Doppler US, color Doppler energy (CDE), or US angiography. Amplitude
      coded color Doppler sonography has already emerged as a valuable adjunct to
      conventional CD, particularly for evaluating flow in parts of the body where CD
      signal is weak because of slow flow, small blood vessels, or both.

PMID- 9933395
TI  - Phase-contrast MR angiography of peripheral arteries: technique and clinical
      application.
AB  - This articles describes Phase-Contrast-MRA (PC-MRA) techniques and their current
      clinical applications for peripheral arteries based on more than 250 clinical MRA
      studies performed at two institutions. PC-MRA depends on phase shifts caused by
      blood flow and thus this technique permits the use of coronal or sagittal slice
      orientations with large FOV's along the direction of the vessel of interest.
      Clinical applications focus on patients with peripheral arterial occlusive
      disease (PAOD) describing the role and limitations of PC-MRA for the work-up of
      stenoses, occlusions, aneurysms, and postsurgical follow-up. Recommendations for
      clinical routine are provided. A combined MR angiographic approach with various
      MRA techniques depending on the vessel segment to be imaged, PC-flow velocity
      measurements, and high-resolution scans of the vessel wall may turn out to be
      diagnostically effective and provide a comprehensive test for PAOD within the
      near future.

PMID- 9933396
TI  - Gadolinium dimeglumine: an alternative contrast agent for digital subtraction
      angiography.
AB  - The aim of this study was to evaluate gadolinium diethylenetriaminepenta-acetic
      acid (Gd-DTPA) as an alternative contrast agent for digital subtraction
      angiography (DSA) in patients with renal insufficiency or previous anaphylactic
      reaction to iodinated contrast agents. We performed 34 DSAs in 31 patients by use
      of the commercially available 0.5-M Gd-DTPA solution (Magnevist, Schering,
      Berlin, Germany). The contrast material was power- or hand-injected at the same
      rate as iodinated contrast material, without exceeding a total amount of 0.4
      mmol/kg body weight. In 18 studies Gd-DTPA was the sole contrast agent. In 9
      cases gadolinium injections were combined with carbon dioxide. Restricted non
      ionic contrast medium injections were administered to complete the examinations
      in 7 cases and for comparative purposes in 1 case. Cerebral and carotid arteries,
      one superior limb, abdominal aorta, renal arteries, renal transplants, iliac
      arteries and inferior limbs were imaged, and ten endovascular interventional
      procedures, including three transjugular intrahepatic percutaneous stent shunts,
      were performed. No side effects were observed. Diagnostic angiographic images
      were obtained in all cases except in 5 of the 8 distal run-off studies.
      Gadolinium-based contrast can produce clinically useful angiograms in patients
      with a contra-indication to iodine who must undergo angiography.

PMID- 9933397
TI  - Value of a laser guidance system for CT interventions: a phantom study.
AB  - The aim of this study was to check the handling and usefulness of a laser
      puncture system. The laser has tacking optics and is fastened to a sledge with
      angle graduation. The sledge runs on a bar fixed to the computerized tomograph
      (CT) parallel to the scan level. By means of a phantom, three experienced and
      seven inexperienced physicians made punctures with and without laser, using
      varying angles in single and double angulation. The distance from needle tip to
      target was measured. The handling of the puncture system proved to be problem
      free. With both single and double angulation, the measurement differences with
      and without support were so small among experienced puncturers that there was no
      significant difference, with the exception of one double angulation (10
      degrees/45 degrees). Among the beginners, there was a significant difference (P <
      0.001, P < 0.05), with both single and double angulation. The accuracy of the
      beginners improved with use of the laser; experienced puncturers may profit from
      practice with small and hard-to-reach focuses. In terms of educational benefits,
      the laser guidance system offers great advantages and increased confidence for
      beginners.

PMID- 9933398
TI  - The correlation between R2' and bone mineral measurements in human vertebrae: an
      in vitro study.
AB  - The aim of this study was to investigate whether MR imaging of trabecular bone
      structure using magnetic inhomogeneity measurements is related to the amount of
      bone mineral in human vertebrae. Weight, bone mineral content (BMCDXA), bone
      mineral per area (BMADXA) and bone mineral density (BMDCT) were determined in 12
      defatted human lumbar vertebrae (L2-L4) by weighing, dual X-ray absorptiometry
      (DXA) and CT. Inhomogeneity caused by susceptibility differences between
      trabecular bone and surrounding water was studied with MR imaging at 1.5 T using
      the GESFIDE sequence. The pulse sequence determines the transverse relaxation
      rate R2(*) and its two components, the non-reversible transverse relaxation rate
      (R2) and the reversible transverse relaxation rate (R2'; i. e. relaxation rate
      due to magnetic susceptibility) in a single scan. Voxel size was 0.9 x 1.9 x 5.0
      mm. Positive significant correlations between R2' and weight, BMCDXA, BMADXA and
      BMDCT were observed (r > 0.61 and p < 0.05 for all). Unexpectedly, R2 was also
      positively correlated with weight, BMCDXA and BMDCT (r > 0.66 and p < 0.05 for
      all), but not with BMADXA. Thus, R2' measurements are related to the amount of
      bone mineral, but they also provide information which is not obtainable from bone
      mineral measurements.

PMID- 9933399
TI  - Degenerative joint disease on MRI and physical activity: a clinical study of the
      knee joint in 320 patients.
AB  - We examined 320 patients with MRI and arthroscopy after an acute trauma to
      evaluate MRI in diagnosis of degenerative joint disease of the knee in relation
      to sports activity and clinical data. Lesions of cartilage and menisci on MRI
      were registered by two radiologists in consensus without knowledge of
      arthroscopy. Arthroscopy demonstrated grade-1 to grade-4 lesions of cartilage on
      729 of 1920 joint surfaces of 320 knees, and MRI diagnosed 14% of grade-1, 32% of
      grade-2, 94% of grade-3, and 100% of grade-4 lesions. Arthroscopy explored 1280
      meniscal areas and showed degenerations in 10%, tears in 11.4%, and complex
      lesions in 9.2%. Magnetic resonance imaging was in agreement with arthroscopy in
      81% showing more degenerations but less tears of menisci than arthroscopy. Using
      a global system for grading the total damage of the knee joint into none, mild,
      moderate, or severe changes, agreement between arthroscopy and MRI was found in
      82%. Magnetic resonance imaging and arthroscopy showed coherently that degree of
      degenerative joint changes was significantly correlated to patient age or
      previous knee trauma. Patients over 40 years had moderate to severe changes on
      MRI in 45% and patients under 30 years in only 22%. Knee joints with a history of
      trauma without complete structural or functional reconstitution showed marked
      changes on MRI in 57%, whereas stable joints without such alterations had
      degenerative changes in only 26%. There was no correlation of degenerative
      disease to gender, weight, type, frequency, and intensity of sports activity.
      Therefore, MRI is an effective non-invasive imaging method for exact localization
      and quantification of chronic joint changes of cartilage and menisci that
      recommends MRI for monitoring in sports medicine.

PMID- 9933400
TI  - Erdheim-Chester disease: a case report and literature overview.
AB  - Erdheim-Chester (EC) disease belongs to the group of lipoid granulomatosis.
      Symmetric sclerosis of the meta- and diaphysis of long tubular bones are
      pathognomonic radiologic changes. Additionally, other skeletal segments can be
      affected. Extraskeletal manifestations can occur in almost all organs; lungs,
      pericardium, retroperitoneum, skin, and orbita play particularly important roles.
      The last case of 38 cases of Erdheim-Chester disease with an extraordinary
      mediastinal and perirenal involvement is described. For the second time following
      the initial description by Chester, an axial skeletal pattern of eburnated
      vertebra is shown.

PMID- 9933401
TI  - Camurati-Engelmann disease: a late and sporadic case with metaphyseal
      involvement.
AB  - A 40-year-old white man with a 3-year history of mild to severe right thigh and
      knee pain was referred for radiographic investigation. Radiographs show a
      fusiform, bilaterally symmetrical enlargement of the diaphyses and metaphyses of
      the long bones (femur, tibia, fibula, radius and ulna). A narrowed medullary
      cavity is illustrated on CT scan of the femur. All bones show periosteal and
      endosteal bone formation. There is no history of familial involvement, trauma,
      infection or systemic illness. Blood chemistry could not point out any
      abnormality. Radiographic findings and clinical history suggest the diagnosis of
      Camurati-Engelmann disease, also known as progressive diaphyseal dysplasia (PDD).
      This case is of interest because of its rare metaphyseal involvement, mild form
      and sporadic presentation.

PMID- 9933402
TI  - MR appearance of pelvic hemangiopericytoma.
AB  - A case of pelvic hemangiopericytoma in a 59-year-old woman is reported. The MR
      imaging features are presented. The tumor was unresectable and the patient
      received postoperative irradiation of 4200 cGy on the pelvis. One year after
      diagnosis, metastasis to a lumbar vertebra was discovered and additional
      irradiation of 3900 cGy was applied. One year later, CT showed control of the
      pelvic tumor and its metastasis.

PMID- 9933403
TI  - Public financing systems for radiology: experience in 12 European countries.
AB  - This paper illustrates the evolution in public health care financing systems in
      12 European countries, in terms of the financing of radiology services. The
      financing systems for radiology used by public health care financing agencies are
      described in detail. The implications of these new financing conditions for
      health care delivery are briefly sketched. The paper concludes with some
      strategies to help radiologists cope with the tightening financing conditions for
      medical imaging.

PMID- 9933404
TI  - Congenital anomalies of tracheobronchial branching patterns: spiral CT aspects in
      adults.

PMID- 9933405
TI  - Idiopathic iliopsoas bursitis.

PMID- 9933406
TI  - Drosophila virilis has atypical kinds and arrangements of histone repeats.
AB  - Genomic and P1 clone DNAs of Drosophila virilis were analyzed to determine the
      structure and organization of histone genes in this species. The species contains
      unique and variable repeat types, in comparison with the related species
      Drosophila melanogaster, with quartet repeats lacking the H1 gene and multi
      length variant quintet repeats containing the H1 gene. Unexpectedly, the H1
      containing repeats are highly polymorphic in length, and thus not in a strict
      tandem arrangement, while the H1-less repeats are very uniform and tandemly
      reiterated. Despite such differences, the relative positions and transcriptional
      polarities of the histone gene subtypes of one subcloned quintet are similar to
      the major histone repeat type of D. melanogaster. For the first time, the histone
      H1 gene has been shown to be associated with other histone gene subtypes and is
      present at both chromosomal loci. DNA sequence variants of the H1 gene have been
      mapped to individual P1 clones and found to be in a partitioned organization. The
      P1 cloning system has proved useful in completely retrieving a complex repetitive
      locus in vitro and in examining the structure and organization of the histone
      genes of D. virilis.

PMID- 9933407
TI  - Localization of SCP2 and SCP3 protein molecules within synaptonemal complexes of
      the rat.
AB  - SCP2 and SCP3 are major protein components of the lateral elements (LEs) of
      synaptonemal complexes (SCs) of the rat, with Mrs of 173, 000 and 30,000. We
      performed a detailed immunocytochemical comparison of the localization of SCP2
      and SCP3 within SCs at the electron microscopic level. The ultrastructural
      localization of SCP2 and SCP3 was analyzed by immunogold labeling of two types of
      preparations, namely surface-spread spermatocytes and ultrathin sections of
      Lowicryl-embedded testicular tissue of the rat. For each of the antisera used,
      the distribution of immunogold label over SCs in surface-spread spermatocytes
      differed significantly from the distribution of label on sections. We attributed
      this difference to artifacts caused by the surface-spreading technique, and
      therefore we relied on sections for the precise localization of epitopes. On
      sections, the distribution of label obtained with two antisera against
      nonoverlapping, widely separated fragments of SCP2 did not differ significantly.
      There was a small but significant difference between the labeling pattern
      obtained with an anti-SCP3 serum and the pattern obtained with either of the two
      antisera against fragments of SCP2; although for all three antisera the peak of
      the immunogold label coincided with the center of the LE, the distributions of
      label obtained with the antisera against fragments of SCP2 were asymmetrical,
      with a shoulder at the inner side of the LE, whereas the distribution of label
      obtained with anti-SCP3 serum was symmetrical. Furthermore, we observed fuzzy
      connections between the LEs that were labeled by anti-SCP2 but not anti-SCP3
      antibodies. It is possible that labeling of these fuzzy bridges caused the
      shoulder in the gold label distributions obtained with anti-SCP2 antibodies.

PMID- 9933408
TI  - Chiasma distributions and chromosome segregation in male and female translocation
      heterozygous mice analysed using FISH.
AB  - Two factors postulated to influence the meiotic behaviour of reciprocal
      translocations were investigated. Firstly, variation in the length of
      translocated and non-translocated segments was studied in male mice using four
      different rearrangements involving chromosomes 2 and 4. Secondly, sex-related
      effects were analysed through comparison of the meiotic behaviour of two
      translocations in male and female germ cells. In the first part of the study,
      primary and secondary spermatocytes of male mice carrying a translocation
      [T(2;4)1Ca, T(2;4)13H, T(2;4)1Sn, or T(2;4)1Go] were screened. Each rearrangement
      had different proportions of cells with ring and chain quadrivalents at metaphase
      I; the T(2;4)1Sn heterozygote also had a high rate (45%) of translocation
      bivalents. In general, the translocations had elevated chiasma frequencies in the
      rearranged chromosomes compared with structurally normal chromosomes 2 and 4,
      although the extent of the effect varied. Each rearrangement produced a different
      array of segregation products at metaphase II, reflecting their contrasting
      frequencies of multivalent configurations at metaphase I. Comparison of
      chromosome behaviour at metaphase I and II suggested that certain configurations
      tended to adopt particular orientations. However, it was also clear that such
      correlations were imprecise and that other factors, possibly the exact positions
      of chiasmata, also played a role in multivalent orientation. Two rearrangements,
      T(2;4)1Go and T(7;16)67H, were analysed in female mice. The frequencies of the
      various multivalent types at metaphase I differed from those in male carriers of
      these rearrangements owing to an increased chiasma frequency in oocytes in some
      of the pairing segments. Not surprisingly, the segregation products seen in
      metaphase II cells showed some differences from the pattern recorded in male germ
      cells. For T(2;4)1Go, the sex-related difference in segregation patterns resulted
      in a diminished expectation of genetically imbalanced gametes, although this was
      not the case for T(7;16)67H.

PMID- 9933409
TI  - The DNA puff gene BhC4-1 of Bradysia hygida is specifically transcribed in early
      prepupal salivary glands of Drosophila melanogaster.
AB  - The BhC4-1 gene of the sciarid Bradysia hygida is located at DNA puff C4 and is
      amplified and actively transcribed in the salivary gland at the end of the last
      larval instar. We show here that a 3.6 kb fragment from the upstream region of
      the BhC4-1 gene is able to drive transcription in transgenic Drosophila
      specifically in prepupal salivary gland in a temporally regulated manner. The
      mRNA is present in maximal amounts in prepupae +3 h; in prepupae +9 h the levels
      of BhC4-1 mRNA decline, and it is no longer detected in pupae +24 h. Taken
      together these results suggest that most, if not all, of the key promoter
      regulatory elements were included in the DNA fragments employed to transform
      Drosophila. Moreover, strong expression of the transgenes implies conservation of
      the regulatory elements involved, since Drosophila transcription factors appear
      to recognize B. hygida regulatory DNA sequences. Quantitative Southern blot
      hybridization indicates that the sequences from DNA puff C4 are not amplified at
      detectable levels in salivary glands of transgenic prepupae when the BhC4-1 gene
      is transcribed. Transcription of a DNA puff in the absence of amplification
      indicates that the induction of these processes involves distinct mechanisms.

PMID- 9933410
TI  - The cenpB gene is not essential in mice.
AB  - Centromere protein B (CENP-B) is a centromeric DNA-binding protein that binds to
      alpha-satellite DNA at the 17 bp CENP-B box sequence. The binding of CENP-B,
      along with other proteins, to alpha-satellite DNA sequences at the centromere, is
      thought to package the DNA into heterochromatin subjacent to the kinetochore of
      mitotic chromosomes. To determine the importance of CENP-B to kinetochore
      assembly and function, we generated a mouse null for the cenpB gene. The deletion
      removed part of the promoter and the entire coding sequence except for the
      carboxyl-terminal 35 amino acids of the CENP-B polypeptide. Mice heterozygous or
      homozygous for the cenpB null mutation are viable and healthy, with no apparent
      defect in growth and morphology. We have established mouse embryo fibroblasts
      from heterozygous and homozygous cenpB null littermates. Microscopic analysis,
      using immunofluorescence and electron microscopy of the cultured cells, indicated
      that the centromere-kinetochore complex was intact and identical to control
      cells. Mitosis was identical in fibroblasts derived from cenpB wild-type,
      heterozygous and null animals. Our studies demonstrate that CENP-B is not
      required for the assembly of heterochromatin or the kinetochore, or for
      completion of mitosis.

PMID- 9933411
TI  - The hsp70 locus of Drosophila auraria (montium subgroup) is single and contains
      copies in a conserved arrangement.
AB  - The restriction endonuclease pattern of a number of hsp70-homologous clones
      isolated from a library of heat shock cDNA from Drosophila auraria, a species
      belonging to the montium subgroup of the melanogaster species group, reveals two
      types of clones, A and B, differing in a single restriction site. Both types, as
      well as hsp70-specific probes derived from both hsp70 loci of Drosophila
      melanogaster, hybridize in situ with a single band at region 32 A of the 2L
      polytene arm, indicating a clustered organization of the hsp70 gene copies in D.
      auraria. The longest type B clone was sequenced and it was found that one strand
      contains an open reading frame (ORF) exhibiting great identity with a previously
      described hsp70 gene of D. auraria (now denoted as type A) and with its
      counterparts of D. melanogaster, while its second strand, unlike the type A
      clone, does not contain a long antiparallel coupled ORF (LAC ORF) because of a
      base substitution resulting in a premature stop codon. After additional data had
      been derived from isolation and characterization of hsp70-homologous genomic
      clones, together with Southern analysis of genomic DNA, we found that two hsp70
      gene copies are present at the above locus of D. auraria with an inverted tandem
      repeat organization, while the presence of a third hsp70 gene is not clearly
      evident. The above results are compared with those observed at the homologous
      loci of some melanogaster subgroup species (D. melanogaster and its sibling
      species), in which, however, the hsp70 locus is duplicated, and with the more
      distantly related Dipteran Anopheles albimanus.

PMID- 9933412
TI  - The chromosomal organization of simple sequence repeats in wheat and rye genomes.
AB  - The physical distribution of ten simple-sequence repeated DNA motifs (SSRs) was
      studied on chromosomes of bread wheat, rye and hexaploid triticale. Oligomers
      with repeated di-, tri- or tetra-nucleotide motifs were used as probes for
      fluorescence in situ hybridization to root-tip metaphase and anther pachytene
      chromosomes. All motifs showed dispersed hybridization signals of varying
      strengths on all chromosomes. In addition, the motifs (AG)12, (CAT)5, (AAG)5,
      (GCC)5 and, in particular, (GACA)4 hybridized strongly to pericentromeric and
      multiple intercalary sites on the B genome chromosomes and on chromosome 4A of
      wheat, giving diagnostic patterns that resembled N-banding. In rye, all
      chromosomes showed strong hybridization of (GACA)4 at many intercalary sites that
      did not correspond to any other known banding pattern, but allowed identification
      of all R genome chromosome arms. Overall, SSR hybridization signals were found in
      related chromosome positions independently of the motif used and showed
      remarkably similar distribution patterns in wheat and rye, indicating the special
      role of SSRs in chromosome organization as a possible ancient genomic component
      of the tribe Triticeae (Gramineae).

PMID- 9933413
TI  - Reduced production of both Th1 and Tc1 lymphocyte subsets in atopic dermatitis
      (AD).
AB  - An imbalance of interferon-gamma (IFN-gamma)-bearing CD4+ T (Th1) cells in the
      pathogenesis of AD is well recognized; however, a possible role in AD for CD8+ T
      cells secreting Th1-like cytokines (Tc1) has not been properly addressed. In this
      study, two- and three-colour FACS analysis allowed us to discriminate the Th1
      from the Tc1 subset. AD patients had half the number of IFN-gamma-producing
      circulating T cells (P < 0.005; 13.6 +/- 1.9% (mean +/- s.d.)) compared with
      normal donors (25.0 +/- 2.4%). Specifically, both Th1 (4.8 +/- 0.7%) and Tc1 (8.1
      +/- 1.1%) cells in AD were decreased compared with Th1 (8.8 +/- 0.8%) and Tc1
      (15.0 +/- 1.5%) cells in controls. Moreover, at the mRNA level, the ratios of IFN
      gamma/IL-4 and IFN-gamma/IL-10 were lower in cells from AD patients compared with
      controls. In conclusion, the decrease of IFN-gamma-producing T lymphocytes in AD
      is due to a reduction in both Th1 and Tc1 IFN-gamma-secreting cells; this may not
      only contribute to the over-production of IgE, but also explain the high
      incidence of cutaneous infections observed in AD patients.

PMID- 9933414
TI  - Swine dust induces cytokine secretion from human epithelial cells and alveolar
      macrophages.
AB  - Exposure to swine dust causes airway inflammation with increased levels of
      proinflammatory cytokines, and inflammatory cells in nasal and bronchoalveolar
      lavage fluid (BALF) in healthy subjects. Earlier studies have suggested that
      lipopolysaccharides (LPS) might be an important proinflammatory factor in swine
      dust. Since respiratory epithelial cells and alveolar macrophages are target
      cells for the inhaled dust, we therefore compared the release of proinflammatory
      cytokines from normal human bronchial epithelial cells (NHBE), an epithelial cell
      line (A549) and from human alveolar macrophages obtained from BALF from healthy
      subjects in vitro after incubation with dust collected in swine houses or LPS.
      Swine dust or LPS was added to the wells with A549 cells or macrophages and
      incubated for 8 h at concentrations of 12.5, 25, 50 and 100 microg/ml. NHBE cells
      were incubated with swine dust at a concentration of 25, 50 or 100 microg/ml or
      with LPS at a concentration of 50 or 100 microg/ml and incubated for 24 h. The
      supernatants were collected, centrifuged, and IL-6, IL-1beta and tumour necrosis
      factor-alpha (TNF-alpha) production was measured using an ELISA method and
      expressed per 106 cells. Swine dust and LPS caused a dose-dependent increase of
      IL-6 production in NHBE cells, swine dust being more potent than LPS. In A549
      cells, only swine dust, but not LPS caused an increase of IL-6 production.
      Neither swine dust nor LPS induced IL-1beta or TNF-alpha release from A549 cells.
      Both swine dust and LPS caused a dose-dependent increase of IL-1beta, IL-6 and
      TNF-alpha in alveolar macrophages. Swine dust which contained 2.2 (0.2) ng
      endotoxin/100 microg swine dust (0.02 per thousand) was almost as potent as LPS
      in inducing cytokine release from alveolar macrophages in vitro. We conclude that
      both epithelial cells and alveolar macrophages have the capability to contribute
      to the release of proinflammatory cytokines following exposure to swine dust.
      Some agent(s) other than LPS in the dust contribute to the marked airway
      inflammatory reaction.

PMID- 9933416
TI  - Abdominal surgery reduces the ability of rat spleen cells to synthesize and
      secrete active tumour necrosis factor-alpha (TNF-alpha) by a multilevel
      regulation.
AB  - We have previously shown that abdominal surgery (explorative laparotomy) reduces
      the ability of lipopolysaccharide (LPS)-triggered spleen macrophages to secrete
      TNF-alpha. In this study we characterize possible mechanisms which could be
      responsible for the reduction in splenic production of TNF-alpha. Post-operative
      and control (unoperated) rat splenocytes or enriched splenic macrophages were
      cultured with LPS. Steady-state levels of TNF-alpha mRNA were determined by
      Northern and slot blot analyses, and validated by quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR). The amount of TNF-alpha protein
      was measured by Western blot analysis, and its biological activity was determined
      by the fibroblast L-929 cytotoxicity assay. Surgery induced a 12-fold inhibition
      in TNF-alpha activity (P < 0.02), caused up to two-fold reduction in the
      accumulation of TNF-alpha mRNA (P < 0.01), and suppressed TNF-alpha protein
      maturation into its 17-kD form in cellular extracts. Post-surgical spleen
      supernatants revealed mainly a band of a lower molecular weight (14 kD). Our data
      suggest a multilevel regulation of post-operative inhibition of TNF-alpha
      response to LPS, at the accumulation of mRNA, translational and secretory levels.
      We also suggest that the reduced bioactivity could be partially caused by a
      proteolytic cleavage of TNF-alpha. Since TNF-alpha is an important participant in
      immune responses, its reduced production and activity may be a central mechanism
      of post-operative immunosuppression.

PMID- 9933415
TI  - Protection of human breast cancer cells from complement-mediated lysis by
      expression of heterologous CD59.
AB  - CD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are
      widely expressed cell surface glycoproteins that protect host cells from the
      effects of homologous complement attack. Complement inhibitory activity of these
      proteins is species-selective. We show that the human breast cancer cell line
      MCF7 is relatively resistant to lysis by human complement, but is effectively
      lysed by rat or mouse complement. CD59, DAF and MCP were all shown to be
      expressed by MCF7. The species-selective nature of CD59 activity was used to
      demonstrate directly the effectiveness of CD59 at protecting cancer cells from
      complement-mediated lysis. cDNAs encoding rat and mouse CD59 were separately
      transfected into MCF7 cells, and cell populations expressing high levels of the
      rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were
      highly effective at protecting transfected MCF7 cells from lysis by rat and mouse
      complement, respectively. Data further reveal that rat CD59 is not effective
      against mouse complement, whereas mouse CD59 is effective against both mouse and
      rat complement. These studies establish a model system for relevant in vivo
      studies aimed at determining the effect of complement regulation on
      tumourigenesis, and show that for effective immunotherapy using complement
      activating anti-tumour antibodies, the neutralization of CD59 and/or other
      complement inhibitory molecules will probably be required.

PMID- 9933417
TI  - Effects of bucillamine and N-acetyl-L-cysteine on cytokine production and
      collagen-induced arthritis (CIA).
AB  - We investigated the effects of bucillamine and N-acetyl-L-cysteine (NAC) on
      cytokine production and CIA. Bucillamine and NAC inhibited NF-kappaB activation
      and tumour necrosis factor-alpha (TNF-alpha) mRNA expression in human monocytic
      leukaemia cell line THP-1, and cytokine production from monocyte cell lines at
      concentrations >10-3 M. They also inhibited cytokine production and CIA in mice
      at a dose of 500 mg/kg. These results suggest that NF-kappaB inhibitors such as
      bucillamine and NAC may inhibit cytokine-related diseases, including arthritis.

PMID- 9933418
TI  - Anti-inflammatory effects of a new tumour necrosis factor-alpha (TNF-alpha)
      inhibitor (CNI-1493) in collagen-induced arthritis (CIA) in rats.
AB  - A recently developed compound, a multivalent guanylhydrazone (CNI-1493) that
      inhibits TNF-alpha production by suppressing TNF-alpha translational efficiency,
      was administered in an experimental model of collagen type II-induced arthritis
      in DA rats. CNI-1493 was injected daily intraperitoneally either before the onset
      of arthritis or after the establishment of clinical disease. Prophylactic
      treatment with CNI-1493 significantly prevented or delayed the onset and
      suppressed the severity of arthritis in a dose-dependent manner. Therapeutic
      intervention with CNI-1493 in established joint disease also resulted in a
      significant reduction of clinical signs of arthritis in treated animals. No
      severe side-effects were noted when animals were treated with daily CNI-1493
      doses up to 5 mg/kg. An immunohistochemical study was performed which
      demonstrated that CNI-1493 led to a reduced expression of TNF-alpha at the site
      of disease activity. Thus, CNI-1493 with documented inhibitory effects on TNF
      alpha synthesis, has proven successful in ameliorating the course of arthritis in
      CIA. We believe that the use of a compound such as CNI-1493 with a defined mode
      of action provides a useful tool for dissecting and understanding important
      pathogenic mechanisms operating in the development of chronic arthritis.

PMID- 9933419
TI  - Methotrexate specifically modulates cytokine production by T cells and
      macrophages in murine collagen-induced arthritis (CIA): a mechanism for
      methotrexate-mediated immunosuppression.
AB  - Immunosuppressive therapy with methotrexate (MTX) has been established as
      effective treatment for patients with rheumatoid arthritis. To analyse the
      therapeutic potential and mechanisms of action of MTX, we determined serum
      cytokine levels and cytokine production by splenic T cells and macrophages in
      untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a
      murine model of experimental arthritis induced by collagen type II (CIA). MTX
      reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by
      splenic T cells but not by macrophages from healthy mice in vitro in a dose
      dependent manner. In contrast, interferon-gamma (IFN-gamma) production was less
      strikingly reduced and IL-4 production was virtually unaffected. In addition,
      treatment of healthy mice with MTX in vivo led to reduced TNF serum levels and
      diminished TNF production by splenic T cells and macrophages. Intraperitoneal
      administration of MTX prior to the onset of arthritis completely prevented
      clinical and pathological signs of CIA. This was associated with a striking
      reduction of TNF production by spleen cells from MTX-treated mice. The role of
      TNF in MTX-mediated effects on cytokine production was further underlined by the
      finding that MTX effects on IFN-gamma production were augmented in TNF-transgenic
      mice but abrogated in mice in which the TNF-alpha gene had been inactivated by
      homologous recombination. Thus, MTX specifically modulates spontaneous and IL-15
      induced TNF-alpha production in mice and prevents experimental murine CIA. These
      data suggest that TNF production by T cells is an important target of MTX and may
      serve as a basis to understand and further analyse MTX-mediated mechanisms of
      immunosuppression in patients with RA.

PMID- 9933420
TI  - Linomide suppresses experimental autoimmune neuritis in Lewis rats by inhibiting
      myelin antigen-reactive T and B cell responses.
AB  - Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses
      several experimental autoimmune diseases. Here we report the effects of Linomide
      on experimental autoimmune neuritis (EAN), a CD4+ T cell-mediated animal model of
      acute Guillain-Barre syndrome (GBS) in humans. EAN induced in Lewis rats by
      inoculation with bovine peripheral nervous system (PNS) myelin and Freund's
      complete adjuvant was strongly suppressed by Linomide administered daily
      subcutaneously from the day of inoculation. Linomide dose-dependently delayed the
      interval between immunization and onset of clinical EAN, as well as the severity
      of EAN symptoms. These clinical effects were associated with dose-dependent down
      modulation of PNS antigen-induced T and B cell responses and with suppression of
      the proinflammatory cytokines IL-12, interferon-gamma (IFN-gamma) and tumour
      necrosis factor-alpha (TNF-alpha) mRNA. In PNS sections, Linomide suppressed IL
      12 and TNF-alpha, and up-regulated IL-10 mRNA expression. These findings suggest
      that Linomide could be useful in certain T cell-dependent autoimmune diseases.

PMID- 9933421
TI  - Experimental melanin-induced uveitis in the Fischer 344 rat is inhibited by anti
      CD4 monoclonal antibody, but not by mannose-6-phosphate.
AB  - Experimental melanin-induced uveitis (EMIU) is a rodent model of acute anterior
      uveitis which was described in 1993. We investigated strain susceptibility, and
      age and gender characteristics of the model, undertook histological and
      immunohistochemical studies to investigate underlying cellular mechanisms, and
      examined several treatment options. Rats were immunized with bovine ocular
      melanin (250 microg), and disease was followed by slit lamp examination. Lewis,
      Fischer 344 and Porton rats were found to be susceptible to EMIU, whereas Wistar
      Furth, DA, and Hooded Wistar strains were resistant. EMIU was neither age- nor
      gender-dependent. In Fischer 344 rats, EMIU was characterized clinically by
      florid anterior segment inflammation. Histopathological findings included
      infiltration of ciliary body and iris with mononuclear cells and neutrophils.
      Both CD4+ and CD8+ T lymphocytes were prominent. Rats were then treated with
      intraperitoneal injections of anti-CD4, anti-CD8 or irrelevant isotype-matched
      MoAb on days -3, 0, 3, 6 and 9 with respect to melanin immunization. Incidence of
      uveitis was significantly reduced in rats treated with a non-depleting cocktail
      of anti-CD4 MoAbs (P = 0.007), whereas a depleting anti-CD8 antibody had no
      effect on the disease. Mannose-6-phosphate inhibits lymphocyte migration in some
      models of T cell-mediated inflammation. This simple sugar was administered to
      additional rats via intraperitoneal osmotic pumps for 14 days following disease
      induction, but did not influence the uveitis. We conclude that EMIU is controlled
      by CD4+ T cells, and disease may be abrogated by treatment with anti-CD4 MoAbs.

PMID- 9933422
TI  - Circulating soluble factor-inhibiting natural killer (NK) activity of fresh
      peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD)
      patients.
AB  - This study was performed in order to assess the cytotoxic activity, both natural
      (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it
      with their clinical features. Cytotoxicity assays were performed using sensitive
      target cells for NK and ADCC activities. In some experiments, highly purified NK
      cells, obtained both by Percoll density gradient and by co-culturing non-adherent
      PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we
      evaluated NK cell parameters such as number, surface expression of adhesion
      molecules (CD11a/CD18, CD49d and CD54) and response to different stimuli. We
      observed a decreased NK cytotoxicity of PBMC from IBD patients, both in
      ulcerative colitis (UC) and Crohn's disease (CD), independently of the clinical
      activity of disease. In contrast, the ADCC lytic activity was within normal
      range. The lower NK cytotoxic activity observed in our IBD patients cannot be
      related to a decreased number of NK cells, surface expression of adhesion
      molecules, defective response to IL-2 and maturative defect. Decreased NK
      activity was induced in PBMC of controls when serum of patients was added and
      this was unrelated to monocyte-derived modulating factor(s). Our data show a
      decreased natural killing by fresh PBMC from IBD patients. This lower activity
      seems to be unrelated to a primary NK cell defect, since purified NK cells
      exhibited normal levels of killing. It might be hypothesized that serum factors,
      possibly derived from lymphocytes, with inhibitory properties on NK activity,
      might be functionally active in the blood of IBD patients, thus modulating NK
      activity.

PMID- 9933423
TI  - Human Th1 responses driven by IL-12 are associated with enhanced expression of
      CD40 ligand.
AB  - IL- 12 is the prominent inducer of Th1 responses in humans and in the mouse. CD40
      ligand (CD40L) plays important roles in regulation of immune responses, including
      T cell-dependent activation of B cells and cytokine production by monocytes and
      dendritic cells. The present study examined the influences of IL-12 on the CD40L
      expression of activated human CD4+ T cells. IL-12 enhanced CD40L expression on
      CD4+ T cells stimulated with immobilized anti-CD3 in the complete absence of
      accessory cells, whereas IL-4 and IL-10 decreased it. Exogenous interferon-gamma
      (IFN-gamma) did not increase CD40L expression on immobilized anti-CD3 stimulated
      CD4+ T cells at any time up to 168 h of culture. The IL-12-induced enhancement of
      CD40L expression on anti-CD3 activated CD4+ T cells was not influenced in the
      presence of a metalloproteinase inhibitor KB8301, which up-regulated CD40L
      expression by preventing the processing of membrane-bound CD40L, or B cells,
      which down-regulated CD40L expression by receptor-mediated endocytosis. These
      results indicate that IL-12 enhances the CD40L expression of activated CD4+ T
      cells independently of the IFN-gamma production. The data thus suggest that Th1
      responses induced by IL-12 might play an important role in the regulation of
      humoral immune responses through up-regulated CD40L expression.

PMID- 9933424
TI  - Cyclooxygenase-1 and -2 are expressed by human T cells.
AB  - In vitro, prostaglandins (PG) have strong inhibitory effects on T cell activation
      and proliferation and inhibitors of PG synthesis (NSAID) increase proliferation
      and activation of T cells. Although most studies have failed to demonstrate
      cyclooxygenase (COX) activity in lymphocytes, there is contradictory evidence on
      the synthesis of different PG. We have studied by reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blot the expression of COX-1 and 
      2 mRNA and protein in resting and activated peripheral blood or Jurkat T cells.
      Cells were activated by T cell receptor triggering with OKT3 antibodies and
      activation confirmed by flow cytometric analysis of surface CD69. COX enzymatic
      activity was measured by determination of arachidonic acid (AA)-induced PG
      synthesis. Both peripheral blood and Jurkat T cells expressed COX-1 and -2 mRNA
      and protein. COX-1 was constitutively expressed and did not change after OKT3
      stimulation. COX-2 was inducible upon OKT3-induced activation. In spite of the
      presence of COX mRNA and immunoreactive protein, AA-induced PG synthesis was not
      detected at the EIA detection (pM) level. The potential role of cyclooxygenases
      in T cells deserves further study, since no PG of the studied series seem to be
      synthesized by T cells.

PMID- 9933425
TI  - Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory
      infections.
AB  - Eighty-six children fed human milk were followed prospectively from birth to 12
      months of age to assess the effect of milk 90K, a secreted glycoprotein with
      immune-stimulatory properties, on development of acute respiratory infections
      (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = 
      0.34; P = 0.001). The average 90K level in human milk fed to children who did
      not develop ARI was significantly higher than in milk fed to children in whom
      infection occurred on multiple occasions (156.6 +/- 144.8 microg/ml versus 70.9
      +/- 92.3 microg/ml; P = 0.001). These data suggest that the protective effects of
      human milk against ARI may be due in part to immune maturation effects by
      secreted 90K.

PMID- 9933426
TI  - Complement depletion aggravates Staphylococcus aureus septicaemia and septic
      arthritis.
AB  - The aim of the study was to assess the role of the complement system in
      Staphylococcus aureus arthritis and septicaemia. The murine model of
      haematogenously acquired septic arthritis was used, injecting intravenously toxic
      shock syndrome toxin-1 (TSST-1), producing S. aureus LS-1. Complement was
      depleted using cobra venom factor (CVF). Evaluation of arthritis was performed
      clinically and histopathologically. In addition, the effect of complement
      depletion on the phagocytic activity of leucocytes was assessed in vivo and in
      vitro. Six days after inoculation of S. aureus the prevalence of arthritis in
      decomplemented mice was three-fold higher than that in controls (91% versus 25%).
      The clinical severity of arthritis at the end of the experiment, expressed as
      arthritic index, was 7.3 and 1.9, respectively. These findings were confirmed by
      histological index of synovitis as well as of cartilage and/or bone destruction
      being significantly higher in decomplemented mice than in controls (9.8 +/- 1.7
      versus 4.9 +/- 1.2, P < 0.05; and 7.9 +/- 1.7 versus 3.0 +/- 0.9, P < 0.05,
      respectively). Also, the septicaemia-induced mortality was clearly higher in
      decomplemented mice compared with the controls. CVF treatment significantly
      reduced in vivo polymorphonuclear cell-dependent inflammation induced by
      subcutaneous injection of olive oil and mirroring the capacity of
      polymorphonuclear cells (PMNC) to migrate and/or extravasate. Besides, the
      decomplementation procedure significantly impaired phagocytic activity of
      peripheral blood leucocytes in vitro, since the number of phagocytes being able
      to ingest bacteria decreased by 50% when the cells were maintained in
      decomplemented serum compared with those in intact serum. The conclusion is that
      complement depletion aggravates the clinical course of S. aureus arthritis and
      septicaemia, possibly by a combination of decreased migration/extravasation of
      PMNC and an impairment of phagocytosis.

PMID- 9933427
TI  - Quantitative and qualitative differences in bronchoalveolar inflammatory cells in
      Pseudomonas aeruginosa-resistant and -susceptible mice.
AB  - The difference in severity of Pseudomonas aeruginosa-induced chronic lung
      infection may be determined by differences in host inflammatory responses. In the
      present study we investigate this possibility using BALB/c and C57Bl/6 mice,
      resistant and susceptible, respectively, to chronic lung infection with P.
      aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar
      beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly
      higher total cell numbers in the bronchoalveolar lavage fluid compared with
      BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in
      C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post
      infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher
      spontaneous production of nitric oxide (NO) at day 7 post-infection compared with
      BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen,
      these cells produced significantly higher NO compared with cells from BALB/c mice
      at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-alpha)
      by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared
      with C57Bl/6 mice, which showed significantly higher levels at day 28 post
      infection. Taken together, these results suggest that defects in the host
      inflammatory process contribute to the variable outcome of chronic lung infection
      with P. aeruginosa. An exaggerated inflammatory response dominated by
      polymorphonuclear cells correlates with susceptibility to infection, whilst a
      modest inflammatory response dominated by macrophages correlates with resistance.
      Moreover, the quantity and timing of production of NO and TNF-alpha by alveolar
      macrophages may modulate the course and outcome of infection.

PMID- 9933428
TI  - Serum concentrations of cytokines in patients with active tuberculosis (TB) and
      after treatment.
AB  - During TB cytokines play a role in host defence. To determine the cytokine
      pattern during various disease stages of TB, serum levels of IL-12, interferon
      gamma (IFN-gamma), IL-4, IL-6 and IL-10 were measured in 81 patients with active
      TB, 15 patients during therapy and 26 patients after anti-tuberculous therapy as
      well as in 16 persons who had been in close contact with smear-positive TB and in
      17 healthy controls. IFN-gamma was elevated during active TB when compared with
      healthy controls, declining during and after treatment. IL-12 (p40 and p70) serum
      levels were not significantly higher in patients with active TB compared with any
      of the other groups. IL-4 levels were low in all groups. IL-6 and IL-10 serum
      levels were elevated in patients with active TB and during treatment. In patients
      with active TB serum levels of IFN-gamma and IL-6 were higher in patients with
      fever, anorexia and malaise. IL-12 levels were higher in patients with a positive
      smear. Cytokine levels did not correlate with localization of TB (pulmonary
      versus extrapulmonary), or skin test positivity. Cytokines directing a Th1
      response (IL-12) or a Th2 response (IL-4) were not elevated in sera of this large
      group of patients with pulmonary and extrapulmonary TB. In patients with active
      TB, cytokines that were elevated in serum were IFN-gamma, IL-6 and IL-10.

PMID- 9933429
TI  - Expression of CD30 mRNA, CD30L mRNA and a variant form of CD30 mRNA in
      restimulated peripheral blood mononuclear cells (PBMC) of patients with
      helminthic infections resembling a Th2 disease.
AB  - It has been proposed that CD30, a member of the tumour necrosis factor (TNF)
      receptor superfamily, is preferentially up-regulated on Th2-type human T cells.
      In order to investigate a correlation between infection with Echinococcus
      multilocularis and CD30 expression, we analysed regulation of CD30 mRNA, a
      variant form of CD30 mRNA (CD30v) and CD30 ligand (CD30L) mRNA expression on PBMC
      from patients with alveolar echinococcosis (AE) using reverse transcriptase
      polymerase chain reaction (RT-PCR). In PBMC of patients with AE as well as
      healthy donors, spontaneous expression of CD30L mRNA and the CD30v mRNA could be
      detected. However, the intact form of CD30 mRNA could be detected neither in
      freshly isolated PBMC of patients nor in PBMC of healthy individuals. Expression
      of CD30L mRNA and the variant form of CD30 mRNA was frequently detected at
      individual time points during 72 h of culture of PBMC stimulated with crude
      Echinococcus antigen. In contrast to CD30v or CD30L mRNA expression, induction of
      CD30 mRNA expression was detected only in three out of six (50%) healthy donors
      and in 10 out of 21 (48%) patients with alveolar echinococcosis after 72 h of
      incubation. As a control, mitogenic stimulation of PBMC of both healthy
      individuals and infected patients led to expression of intact CD30 mRNA within 24
      h of culture. These data demonstrate the different expression of two different
      forms of CD30 mRNA in PBMC of human individuals. The specific induction of CD30
      expression is correlated only in rare cases with the clinical status of patients
      with AE, indicating the lack of a general induction of CD30 mRNA in this Th2-type
      dominated helminthic disease. The data provide further evidence that the CD30
      receptor is not an exclusive marker for a Th2-type response.

PMID- 9933430
TI  - Circulating cytokine balance and activation markers of leucocytes in Q fever.
AB  - As Q fever is associated with an inflammatory syndrome, we determined circulating
      levels of inflammatory cytokines, cytokine antagonists, and activation markers of
      leucocytes in patients with acute Q fever and Q fever endocarditis. Tumour
      necrosis factor (TNF) and IL-6, but not IL-1beta, were markedly increased
      compared with controls. Cytokine antagonists and activation markers of leucocytes
      were profoundly different in acute and chronic Q fever. IL-1 receptor antagonist
      and TNF receptor type II were significantly increased in patients with acute Q
      fever, suggesting a shift of cytokine balance towards cytokine antagonists. The
      activation marker of B cells, sCD23, was significantly increased in Q fever
      endocarditis compared with controls and patients with acute Q fever. In a 2-year
      follow-up study of patients with Q fever endocarditis, sCD23 and specific IgG
      levels slowly decreased in patients whose symptoms resolved, but remained high in
      those who required prolonged treatment.

PMID- 9933431
TI  - Existence of activated and memory CD4+ T cells in peripheral blood and their skin
      infiltration in CD8 deficiency.
AB  - CD8 deficiency is a rare primary immunodeficiency caused by the defect of a
      tyrosine kinase, ZAP-70, which transduces signals from the T cell receptor. We
      report here a case of CD8 deficiency, having CD4+ T cells with a unique
      phenotype. The patient's T cells did not respond to anti-CD3 stimulation in
      vitro, suggesting that they were naive. However, many CD4+ T cells with activated
      and memory phenotypes, which expressed CD45RO+, HLA-DR+ and CD25+, were present
      in the peripheral blood, and these cells accumulated in the perivascular area of
      his infiltrative erythematous skin lesions. The patient's T cells could be
      activated by a high concentration of phytohaemagglutinin (PHA), indicating the
      presence of an alternate signalling pathway which bypasses ZAP-70 and activates
      CD4+ T cells in vivo. The origin and role of activated CD4+ T cells in the
      pathogenesis involved in the skin lesions are discussed.

PMID- 9933432
TI  - Systemic immune response after intravesical instillation of bacille Calmette
      Guerin (BCG) for superficial bladder cancer.
AB  - The mechanism of anti-tumour activity by BCG is not known clearly. However, many
      studies suggest that immunological response is related to effectiveness of
      intravesical instillation of BCG in the therapy for superficial bladder
      carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were
      obtained from patients with superficial carcinoma at various times during the
      course of BCG instillation. Urine of patients showed increased levels of IL
      1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma
      (IFN-gamma) and macrophage colony-stimulating factor (M-CSF) after BCG
      instillation. Levels of IL-2 and IFN-gamma in the serum also increased after BCG
      instillation, but IL-1beta, IL-6, TNF-alpha and M-CSF were not detectable.
      Maximal levels of IL-2 and IFN-gamma in the urine or serum were shown after the
      fourth instillation. BCG-induced killer cell activity in PBMC increased
      significantly after the third BCG instillation. These results suggest that BCG
      instillation involved not only local immunological efforts but also systemic
      immune responses. Tumour-free patients produced higher BCG-induced killer cell
      activity than tumour recurrence patients. BCG-induced killer cell activity may be
      useful for monitoring the effectiveness of intravesical BCG instillation.

PMID- 9933433
TI  - Administration of intravenous immunoglobulin (IVIG) in vivo--down-regulatory
      effects on the IL-1 system.
AB  - Modulation of the cytokine network may be of importance for the beneficial
      effects of therapy with IVIG seen in a wide range of immune-mediated disorders.
      In the present study we investigate the effect of IVIG administration in vivo on
      the IL-1 system in 12 patients with primary hypogammaglobulinaemia. Before IVIG
      infusion these patients had significantly elevated levels of IL-1alpha and IL
      1beta both in plasma and in supernatants from peripheral blood mononuclear cells
      (PBMC) compared with healthy controls. After one bolus infusion with IVIG (0.4
      g/kg) we found a significant change in the profile of the components of the IL-1
      system: a marked increase in levels of IL-1 receptor antagonist (IL-1Ra) and
      neutralizing antibodies against IL-1alpha, a moderate decrease in levels of IL
      1alpha, IL-1beta and soluble (s) IL-1 receptor type I and a significant increase
      in sIL-1 receptor type II levels. These changes were found both in plasma and in
      PBMC isolated after IVIG administration. Furthermore, pooled serum obtained after
      IVIG infusion suppressed lipopolysaccharide- and staphylococcal enterotoxin B
      stimulated, but not phorbol myristate acetate-stimulated, release of IL-1alpha
      and IL-1beta from PBMC isolated from healthy controls. Finally, these changes in
      circulating levels of various IL-1 modulators after IVIG infusion appeared to
      cause a significantly impaired ability of IL-1 to stimulate PBMC for tumour
      necrosis factor-alpha release. Our findings suggest that IVIG administration may
      not only down-regulate the activity in the IL-1 system, but also hamper IL-1
      stimulation of PBMC.

PMID- 9933434
TI  - Successful immunomodulating in AIDS patients with ursodeoxycholic acid--a pilot
      study.
AB  - Based on the positive therapeutic results with ursodeoxycholic acid (UDCA) in
      patients with primary biliary cirrhosis, in whom we observed a clinical
      improvement in conjunction with the normalization of the low pretreatment
      dipeptidyl peptidase (DPIV, CD26) expression of peripheral blood lymphocytes
      (PBL), we hypothesized that the very low DPIV expression in AIDS patients could
      be positively influenced by UDCA. Four young male AIDS patients were therefore
      treated with 750 mg of UDCA for 4 months. The low CD26 expression (2-8% of the
      PBL versus 18-28% in healthy controls) at the beginning of the study rose to 10
      16% after UDCA therapy. Simultaneously we observed a two-to-three-fold elevation
      of the absolute number of lymphocytes as well as a slight increase of CD4+ cells.
      These effects were similar in all examined patients. Further investigations
      should be conducted on this potentially beneficial effect of UDCA.

PMID- 9933435
TI  - Effect of protease therapy on cytokine secretion by peripheral blood mononuclear
      cells (PBMC) from HIV-infected subjects.
AB  - The viral load reduction seen in patients with late stage HIV infection treated
      with the protease inhibitor, ritonavir, is accompanied by increases in the in
      vitro proliferative responses generated by PBMC. The present study was undertaken
      to investigate which lymphocyte subsets generated these responses and the effects
      of therapy on cytokine production. Lymphoproliferation following
      phytohaemagglutinin (PHA) stimulation was studied by thymidine incorporation, and
      production of IL-2, interferon-gamma (IFN-gamma) and IL-4 was assessed by ELISA
      in 12 patients receiving ritonavir and seven receiving placebo in the context of
      randomized, blinded clinical trials. CD4+ cell-depleted and CD8+ cell-depleted
      subsets were obtained from PBMC by immunomagnetic bead depletion. At week 4 of
      therapy a two-fold or greater increase in proliferative responses was observed in
      9/12 subjects receiving therapy, compared with 0/7 receiving placebo. Similarly
      there was a significant increase in IL-2 and IFN-gamma production of 2.7-fold (P
      = 0.02) and 1.7-fold (P = 0.03), respectively, in the treatment group compared
      with those receiving placebo. No change in IL-4 production was observed. Despite
      these increases, cytokine responses post-therapy were still reduced compared with
      both healthy controls and asymptomatic HIV-infected subjects. Increases in
      proliferative response and IL-2 production were greater in the CD8+ cell-depleted
      population than in the CD4+ cell-depleted population, whereas increases in IFN
      gamma production were derived from the CD4+ cell-depleted population.

PMID- 9933436
TI  - Differential expression of costimulatory molecules in chronic inflammatory
      periodontal disease tissue.
AB  - Although B cell activation and subsequent immunoglobulin production are the
      immunopathological features of chronic inflammatory periodontal disease, in situ
      expression of costimulatory molecules in humoral immunity has not been
      investigated. In the present study we examined the expression of CD40, CD40
      ligand (CD40L), CD80, CD86, CD28 and cytolytic T lymphocyte-associated antigen-4
      (CTLA-4) on lymphocytes immunohistochemically. Cryostat sections were prepared
      from the gingival tissue samples of 14 patients with moderate to advanced adult
      periodontitis. In vitro kinetics of the expression of CD40L and CTLA-4 by
      peripheral blood T cells and that of CD80 and CD86 by peripheral blood B cells
      were also investigated by flow cytometry. Positive percentage expression of
      CD40L, CD28 and CTLA-4, and CD40, CD80 and CD86 was calculated for the number of
      CD3+ and CD19+ cells, respectively. Flow cytometric analysis demonstrated that
      the expression of CD40L and CTLA-4 on T cells, and CD80 and CD86 on B cells of
      peripheral blood was up-regulated upon activation. While most T cells and B cells
      expressed CD28, and CD80 and CD86, respectively, in gingival tissues, the
      expression of CD40L and CTLA-4 was lower but highly variable between specimens.
      Furthermore, these two molecules seemed to be expressed reciprocally in the
      lesion. As both CD40L and CTLA-4 expression are induced transiently by
      stimulation, variability in the expression of the molecules may reflect
      immunological activities and participation in the regulation of B cell activation
      of the lesion.

PMID- 9933437
TI  - CD40 engagement modulates the production of matrix metalloproteinases by gingival
      fibroblasts.
AB  - Chronic periodontitis is a destructive inflammatory disease linked with
      unbalanced production between matrix metalloproteinases (MMPs), such as
      interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) and their endogenous
      tissue inhibitors of MMPs (TIMPs). In addition to aberrant MMP-1 and MMP-3
      expression, periodontal lesions are characterized by dense infiltrations of
      activated T lymphocytes which may interact with CD40-expressing gingival
      fibroblasts in the connective tissue via the CD40L-CD40 pathway. In this study we
      investigated whether CD40 cross-linking influenced MMP production by gingival
      fibroblasts. Therefore, we analysed the CD40L-induced MMP production by these
      fibroblasts in the presence of cytokines that are increased in periodontal
      lesions, such as IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma). We show that CD40 ligation on gingival fibroblasts
      resulted in a decrease of their MMP-1 and MMP-3 production, while MMP-2 and TIMP
      1 production were unaffected as determined by Western blot. This down-regulatory
      effect of CD40 engagement on MMP-1 and MMP-3 production by gingival fibroblasts
      was also present when MMP production was up-regulated by IL-1beta and TNF-alpha
      or down-regulated by IFN-gamma. These results suggest that CD40 ligation on
      gingival fibroblasts leads to a restraining of MMP-1 and MMP-3 production by
      gingival fibroblasts and thereby may be an important mechanism in the retardation
      of further periodontal tissue damage.

PMID- 9933438
TI  - Molecular analysis of rheumatoid factor (RF)-negative B cell hybridomas from
      rheumatoid synovial tissue: evidence for an antigen-induced stimulation with
      selection of high mutated IgVH and low mutated IgVL/lambda genes.
AB  - The mutational pattern of IgVH and IgVL genes from synovial tissue B cell
      hybridomas (n = 8) of patients (n = 4) with rheumatoid arthritis (RA) was
      analysed, which had been produced by the electrofusion technique without prior in
      vitro stimulation. The molecular data were correlated with
      immunohistopathological data and parameters of local disease activity. The IgVH
      genes of the B cell hybridomas belonged to the VH3 family (DP42; DP47, n = 2;
      DP53), the VH1 family (DP75), the VH4 family (DP71) and the VH5 family (DP73);
      7/7 IgVH genes showed somatic mutations, the R/S ratio (CDR) was > 3 in 4/7 IgVH
      genes and the mean R/S ratio of all IgVH genes was 9.3 (CDR) and 1.0 (FR),
      suggesting an antigen-dependent selection. The IgVL/lambda genes belonged to the
      Vlambda1 family (DPL2, DPL5, DPL8nf), the Vlambda2 family (DPL11, n = 2) and to
      the Vlambda6 family (IGLV6S1); 6/6 IgVL genes showed somatic mutations, the R/S
      ratio (CDR) was > 3 in 3/6 IgVL genes and the mean R/S ratio of all IgVL was 3.0
      (CDR) and 2.3 (FR), suggesting an antigen-dependent selection. The synovial
      tissue exhibited germinal centres in the follicles (3/4), with the unique
      distribution of Ki-M4+ follicular dendritic cells and Ki-67+ proliferating cells
      and a dominance of IgA+ plasma cells (3/3). All patients were positive for RF in
      serum and exhibited severe local symptoms (swelling 4/4; warmth 4/4; effusion
      2/4), whereas the hybridomas were negative for RF. Since B cell hybridomas showed
      hypermutation and affinity selection for IgVH and IgVL/lambda genes and the
      patients exhibited severe local symptoms with germinal centres in synovial
      tissue, this study indicates that an antigen-driven process is behind the B cell
      expansion in the synovial tissue of clinically affected joints. These mutated B
      hybridomas were negative for RF, thus suggesting that antigens different from RF
      are also involved in the local B cell expansion and in the chronic synovitis of
      RA.

PMID- 9933439
TI  - Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)
      induced vascular endothelial growth factor secretion by human synovial
      fibroblasts.
AB  - Vascular endothelial growth factor (VEGF) is abundant in synovium and synovial
      fluids, where it probably contributes to vascular permeability and angiogenesis
      in arthritic joints. To investigate the probable sources of VEGF in synovium, we
      compared the ability of several cytokines (TGF-beta, platelet-derived growth
      factor (PDGF), IL-1, tumour necrosis factor (TNF), basic fibroblast growth factor
      (bFGF) that are associated with arthritis and angiogenesis, to stimulate
      secretion of VEGF protein by human synovial fibroblasts. TGF-beta was the
      strongest inducer of VEGF secretion; six times more VEGF was secreted when cells
      were stimulated by TGF-beta than when stimulated by PDGF or IL-1 for 24 h. TNF
      alpha and bFGF did not stimulate any secretion of VEGF. The stimulatory effects
      of TGF-beta and IL-1 on VEGF secretion were additive. Hypoxic culture alone also
      stimulated VEGF secretion, but more importantly, hypoxic culture conditions
      doubled the rate of VEGF secretion stimulated by the cytokines TGF-beta and IL-1.
      When dermal and synovial fibroblasts were stimulated identically by hypoxia and
      cytokines (TGF-beta and IL-1), synovial fibroblasts secreted four times more VEGF
      than did dermal fibroblasts. Thus in rheumatoid arthritis, the capacity of
      synovial fibroblasts in the hypoxic environment to secrete large amounts of VEGF
      in response to cytokines such as TGF-beta probably contributes significantly to
      angiogenesis in the synovium.

PMID- 9933440
TI  - High IgE in rheumatoid arthritis (RA) patients is complexed with anti-IgE
      autoantibodies.
AB  - This study presents data on more than 300 RA and allergic patients analysed for
      their serum levels of anti-immunoglobulin isotype autoantibodies and IgE. We
      observed high levels of IgE in sera of RA and allergic patients. Interestingly,
      we measured significantly higher specific IgE levels against Alternaria but not
      against nine other allergens in the RA compared with the allergic group. As
      expected, anti-IgG autoantibodies (rheumatoid factors (RF)) of different isotypes
      were detected in sera from RA patients only. However, we found increased titres
      of complexed anti-IgE autoantibodies in all RF+ groups and in the allergic group.
      These findings may explain why despite elevated IgE levels a decreased prevalence
      of allergic diseases in RA patients has been observed.

PMID- 9933441
TI  - Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine
      production by peripheral blood mononuclear cells (PBMC) from patients with
      systemic lupus erythematosus (SLE).
AB  - We investigated the production of IL-2, IFN-gamma, IL-10 and IL-4 by PBMC from 24
      patients with SLE and 10 healthy individuals. Basal and mitogen-stimulated
      (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was
      determined in a whole blood assay (WBA). Supernatants were collected and assayed
      with specific ELISAs. Although the IL-2 and IFN-gamma contents did not differ
      significantly between patients and controls under both conditions, statistically
      significant correlations were found between each cytokine and disease activity
      (SLAM index) after stimulation (respectively, r = 0.501, P = 0.01 and r = 0.631,
      P = 0.001). PBMC IL-10 production was significantly higher for patients than
      controls (P = 0.05), but no correlation between IL-10 levels and the SLAM index
      was obtained. IL-4 production was not statistically different between SLE
      patients and controls. For stimulated WBAs, the IL-10/IL-2 and IL-10/IFN-gamma
      ratios were significantly correlated with disease severity (P = 0.02; P = 0.001,
      respectively). Overall, our data suggest that SLE is characterized by an elevated
      production of IL-10, reflecting the basal state of activation of the immune
      system. During exacerbation of SLE, IL-2 and IFN-gamma are synthesized in larger
      amounts and may cause the tissue damage observed.

PMID- 9933442
TI  - Patients with systemic lupus erythematosus (SLE) have a circulating inducer of
      interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature
      dendritic cells.
AB  - Patients with active SLE often have an ongoing production of IFN-alpha. We
      therefore searched for an endogenous IFN-alpha-inducing factor (IIF) in SLE
      patients and found that their sera frequently induced production of IFN-alpha in
      cultures of peripheral blood mononuclear cells (PBMC) from healthy blood donors,
      especially when the PBMC were costimulated with the cytokines IFN-alpha2b and
      granulocyte-macrophage colony-stimulating factor (GM-CSF). The phenotype of the
      IFN-alpha-producing cells (IPC) as determined by flow cytometry corresponded to
      that of the natural IPC, resembling immature dendritic cells. The IIF activity in
      SLE sera was sometimes as high as that of a virus and was present especially in
      patients with active disease and with measurable IFN-alpha levels in serum. The
      IIF had an apparent molecular weight of 300-1000 kD and appeared to consist of
      both immunoglobulin and DNA, possibly being immune complexes. This endogenous IFN
      alpha inducer may be of pathogenic significance, since a reported occasional
      adverse effect of IFN-alpha therapy in patients with non-autoimmune disorders is
      development of anti-dsDNA antibodies and SLE.

PMID- 9933443
TI  - Ro/SS-A-reactive B lymphocytes in salivary glands and peripheral blood of
      patients with Sjogren's syndrome.
AB  - The aim of this study was to investigate the production of anti-Ro/SS-A
      antibodies in labial salivary glands (LSG) and peripheral blood (PB) of Sjogren's
      syndrome (SS) patients. The ELISPOT method was performed to quantify the
      frequency of LSG lymphocytes and PB lymphocytes spontaneously secreting anti
      Ro/SS-A antibodies. The total number of IgG-, IgA- and IgM-producing cells was
      also quantified. The bovine Ro 60-kD protein was used as target antigen. Six of
      six primary SS patients had LSG B cells producing anti-bovine Ro 60 kD of the IgG
      isotype, and two of two primary SS patients had in addition PB lymphocytes
      producing anti-bovine Ro 60 kD of the IgG isotype. The six patients who had IgG
      antibodies against the Ro/SS-A antigen in LSG all had focus scores of >/= 7 in
      biopsies of LSG. The results indicate that SS patients with a high degree of
      local inflammation in LSG have B cells producing anti-Ro/SS-A antibodies in both
      LSG and PB. Thus, the anti-Ro/SS-A antibodies may have pathogenic importance in
      the progression of the exocrinopathy of SS.

PMID- 9933444
TI  - Ro/SS-A- and La/SS-B-reactive B lymphocytes in peripheral blood of patients with
      Sjogren's syndrome.
AB  - The aim of this study was to investigate the production of anti-Ro/SS-A and anti
      La/SS-B antibodies in peripheral blood (PB) of patients with Sjogren's syndrome
      (SS). The ELISPOT method was performed to quantify the frequency of PB
      lymphocytes spontaneously secreting anti-Ro/SS-A and/or anti-La/SS-B antibodies.
      The total number of IgG-, IgA- and IgM-producing cells was also quantified. The
      recombinant Ro 52-kD, Ro 60-kD and La 48-kD proteins were used as target
      antigens. Three of 18 SS patients had PB lymphocytes secreting IgG antibodies
      against the recombinant Ro 52-kD protein. The same three patients had high serum
      titres of anti-Ro 52-kD antibodies. In addition, these patients were classified
      as having severe disease, and all three had focus scores of >/= 8 in biopsies of
      the labial salivary glands (LSG). The correlation between the number of PB cells
      producing IgG antibodies against the recombinant Ro 52-kD protein and the focus
      score was significant (P < 0.01). The results indicate that only SS patients with
      severe disease and high degree of local inflammation in LSG have B cells
      producing anti-Ro/SS-A antibodies in PB. Thus, most of the spontaneous
      autoantibody production must take place in other body compartments, e.g. in
      exocrine glands and probably also in the lymphoid organs and/or other mucosal
      sites.

PMID- 9933445
TI  - Beta2-glycoprotein I (beta2-GPI) mRNA is expressed by several cell types involved
      in anti-phospholipid syndrome-related tissue damage.
AB  - We report here the expression of beta2-GPI mRNA by cell types involved in the
      pathophysiology of the anti-phospholipid syndrome (APS), i.e. endothelial cells
      as a target of autoantibodies in the APS, astrocytes and neurones involved in APS
      of the central nervous system (CNS). Lymphocytes were also included in the study,
      as it has been demonstrated that patients with systemic lupus erythematosus
      associated CNS diseases have serum anti-lymphocyte antibodies cross-reacting with
      brain antigens, and intrathecally synthesized anti-neurone antibodies. Reverse
      transcriptase-polymerase chain reaction followed by restriction enzyme digestion
      of the product obtained demonstrated the presence of beta2-GPI mRNA in all cell
      types here tested, cultured both in presence and absence of fetal calf serum. In
      both culture conditions, the same cell types were immunoreactive to an anti-beta2
      GPI MoAb, as determined by indirect immunofluorescence technique. Taken together,
      these results indicate a direct cell synthesis of beta2-GPI, suggesting an
      antigenic function of beta2-GPI in the APS, including the CNS disease that occurs
      in this syndrome.

PMID- 9933446
TI  - Inhibition of murine IgE and immediate cutaneous hypersensitivity responses to
      ovalbumin by the immunomodulatory agent leflunomide.
AB  - Leflunomide has been identified as an immunoregulatory and anti-inflammatory
      compound. Allergic disease is characterized by elevated serum IgE levels,
      production of allergen-specific IgE and the release of inflammatory mediators
      from mast cells and granulocytes. Here we demonstrate, using an in vivo murine
      model, the ability of leflunomide to down-regulate levels of total and allergen
      specific serum IgE production. Mice receiving leflunomide (45 mg/kg) orally at
      the time of primary immunization with ovalbumin adsorbed to aluminium hydroxide
      adjuvant, showed a reduction in total serum IgE levels of 95%, 41% and 32%
      following primary, secondary and tertiary immunizations, respectively (P < 0.05).
      When leflunomide was administered both at the time of primary and subsequent
      immunizations, reductions in total and specific serum IgE levels of > 80% and >
      38%, respectively, were observed (P < 0.05). Administration of leflunomide to
      mice which had already developed an IgE response resulted in reductions in total
      and specific serum IgE levels of > 80% and > 45%, respectively (P < 0.05).
      Following leflunomide treatment, animals failed to develop immediate cutaneous
      hypersensitivity responses when challenged intradermally with allergen. Down
      regulation of immunoglobulin production was not restricted to IgE, since levels
      of allergen-specific IgG1 and IgG2a in serum were also reduced. The finding of
      significant reductions in total and allergen-specific IgM suggests that the
      mechanism of action does not involve selective inhibition of immunoglobulin class
      switching. A loss in production of the T helper cell-derived B cell
      differentiation factor IL-5 may account for the reduction in immunoglobulin
      levels. In adoptive transfer experiments leflunomide did not induce tolerance in
      allergen-reactive Th2 populations, contrary to animal disease models of
      transplantation and autoimmunity, where leflunomide was shown to induce tolerance
      in the effector T cell population.

PMID- 9933447
TI  - Regulation of CR3 (CD11b/CD18)-dependent natural killer (NK) cell cytotoxicity by
      tumour target cell MHC class I molecules.
AB  - Phagocyte and NK cell CR3 functions as both an adhesion molecule and an iC3b
      receptor mediating cytotoxic responses to microorganisms. Cytotoxic activation of
      iC3b receptor function requires ligation of both a CD11b I-domain site for iC3b
      and a lectin site located in the C-terminus of CD11b. Because tumours lack the
      CR3-binding polysaccharides of bacteria and fungi, iC3b-opsonized tumours do not
      stimulate CR3-dependent cytotoxicity. Previous studies showed that NK cells could
      be induced to kill iC3b-opsonized tumours with small soluble beta-glucans that
      bound with high affinity to CR3, bypassing the absence of similar polysaccharides
      on tumour membranes. Because CR3 signalling requires several tyrosine
      phosphorylation events, it appeared possible that CR3-dependent killing of
      autologous tumour cells might be suppressed by NK cell inhibitory receptors for
      MHC class I (KIR and CD94/NKG2) whose action involves recruitment of SHP-1 and
      SHP-2 tyrosine phosphatases. In the current study, Epstein-Barr virus (EBV)
      transformed B cells were used as targets following opsonization with iC3b.
      Soluble beta-glucan primed CR3 for killing of iC3b-coated B cells, but autologous
      class I-bearing targets were 84% more resistant than class I-deficient Daudi
      cells. Blockade of target cell class I with a MoAb specific for a domain
      recognized by both KIR and CD94/NKG2 resulted in comparable killing of class I+ B
      cells. By contrast, another MoAb to class II had no effect on cytotoxicity. These
      data suggest that NK cell recognition of class I suppresses CR3/tyrosine kinase
      dependent cytotoxicity in the same way as it suppresses cytotoxicity mediated by
      other tyrosine kinase-linked receptors such as FcgammaRIIIA (CD16).

PMID- 9933449
TI  - Mechanisms of Mycobacterium avium-induced resistance against insulin-dependent
      diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice: role of Fas and Th1
      cells.
AB  - NOD mice spontaneously develop autoimmune diabetes. One of the manipulations that
      prevent diabetes in NOD mice is infection with mycobacteria or immunization of
      mice with mycobacteria-containing adjuvant. Infection of NOD mice with
      Mycobacterium avium, done before the mice show overt diabetes, results in
      permanent protection of the animals from diabetes and this protective effect is
      associated with increased numbers of CD4+ T cells and B220+ B cells. Here, we
      investigate whether the M. avium-induced protection of NOD mice from diabetes was
      associated with changes in the expression of Fas (CD95) and FasL by immune cells,
      as well as alterations in cytotoxic activity, interferon-gamma (IFN-gamma) and IL
      4 production and activation of T cells of infected animals. Our data indicate
      that protection of NOD mice from diabetes is a Th1-type response that is mediated
      by up-regulation of the Fas-FasL pathway and involves an increase in the
      cytotoxicity of T cells. These changes are consistent with induction by the
      infection of regulatory T cells with the ability of triggering deletion or anergy
      of peripheral self-reactive lymphocytes that cause the autoimmune disease of NOD
      mice.

PMID- 9933448
TI  - IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is
      indicative of a Th1-like autoimmune disease.
AB  - Studies performed in mice together with the demonstration of increased levels of
      heart-specific autoantibodies, cytokines and cytokine receptors in sera from
      cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune
      mechanisms in CMP. This study was designed to analyse the presence of IgG anti
      heart antibodies in sera from patients suffering from hypertrophic and dilatative
      forms of CMP as well as from patients with ischaemic heart disease and healthy
      individuals. Patients' sera were analysed for IgG reactivity to Western-blotted
      extracts prepared from human epithelial and endothelial cells, heart and skeletal
      muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1
      4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera
      from CMP patients and healthy individuals displayed comparable IgG reactivity to
      a variety of human proteins, cardiac myosin represented the prominent antigen
      detected strongly and preferentially by sera from CMP patients. Pronounced IgG
      anti-cardiac myosin reactivity was frequently found in sera from patients with
      dilatative CMP and reduced ventricular function. ELISA analyses revealed a
      prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a
      preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti
      enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S.
      pyogenes proteins were also frequently observed in the group of CMP patients. If
      further work can support the hypothesis that autoreactivity to cardiac myosin
      represents a pathogenic factor in CMP, specific immunomodulation of this Th1-
      towards a Th2-like immune response may represent a promising therapeutic strategy
      for CMP.

PMID- 9933451
TI  - The pathogenicity of islet-infiltrating lymphocytes in the non-obese diabetic
      (NOD) mouse.
AB  - The aim of the present study was to investigate the pathogenic properties of
      islet-infiltrating lymphocytes related to the severity of the autoimmune
      destruction of islet beta-cells in the NOD mouse. We analysed the development of
      insulin-dependent diabetes mellitus (IDDM) produced by adoptive transfer of islet
      lymphocytes from NOD into NOD.scid mice. Here we show that the transfer was most
      effective when both CD4+ and CD8+ T cells were present in the infiltrate, but
      CD4+ T cells alone were sufficient to cause the disease. Islet lymphocytes from
      both females and males transferred diabetes effectively, but the severity of IDDM
      was higher when female islet lymphocytes were used. Unexpectedly, the sensitivity
      of male islets to beta-cell damage was greater than that of female islets.
      Treatment of NOD females with a peptide of heat shock protein (hsp)60, p277,
      known to protect NOD mice from IDDM, reduced the pathogenicity of the islet
      lymphocytes. In contrast, administration of cyclophosphamide to males, a
      treatment that accelerates the disease, rendered the islet lymphocytes more
      pathogenic. More severe disease in the recipient NOD.scid mice was associated
      with more interferon-gamma (IFN-gamma)-secreting islet T cells of the NOD donor.
      The disease induced by islet lymphocytes was strongly inhibited by co-transfer of
      spleen cells from prediabetic mice, emphasizing the regulatory role of peripheral
      lymphocytes. Thus, the cellular characteristics of the islet infiltrate and the
      pathogenicity of the cells are subject to complex regulation.

PMID- 9933450
TI  - Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes
      mellitus: increased prevalence and relation to vascular complications.
AB  - Anti-cardiolipin antibodies, oxidatively modified low-density lipoproteins
      (oxLDL) and circulating immune complexes are humoral factors that have been
      linked to vascular damage. To analyse their possible role in the vascular
      complications in type 1 diabetes mellitus, we investigated patients with and
      without vascular complications (retinopathy, nephropathy, polyneuropathy, foot
      ulcers). The patients were matched for age, sex and duration of diabetes. The
      patients were also compared with 102 healthy individuals. Anti-cardiolipin
      antibodies of IgG and IgA type were more common in patients compared with healthy
      individuals. There was no difference between patients with and without vascular
      complications. There was no increased prevalence of IgM anti-cardiolipin
      antibodies, but the levels of these antibodies were higher in patients with
      vascular complications compared with patients without complications and controls.
      Eighty-three percent of patients had circulating immune complexes in comparison
      with 5% of healthy individuals. Such complexes were more common in patients with
      complications. Both the prevalence and the levels of immune complexes were higher
      in patients with null alleles of complement factor C4. Patients with vascular
      complications had higher prevalence of C4A than of C4B null alleles. Anti
      cardiolipin antibodies were present in higher relative concentrations in immune
      complex form than in serum in all six patients analysed. There was no increased
      prevalence of antibodies against oxidatively modified LDL in the patients. The
      higher prevalence and levels of anti-cardiolipin antibodies and circulating
      immune complexes in patients with vascular complications suggests that these
      humoral factors might be involved in the vascular complications of type 1
      diabetes mellitus.

PMID- 9933452
TI  - Molecular chaperones are targets of autoimmunity in Ro(SS-A) immune mice.
AB  - We have used a murine model of experimental anti-Ro(SS-A) autoimmunity to dissect
      additional intermolecular interactions between the 52-kD Ro (Ro52) and 60-kD Ro
      (Ro60) autoantigens and molecular chaperones. Immune responses to members of the
      heat shock protein hsp70 and hsp90 families were measured by immunoblotting and
      ELISA in sera from mice immunized and boosted with purified recombinant Ro52,
      Ro60 and La (SS-B). All Ro52 and Ro60 immune sera immunoblotted the inducible
      glucose-regulated protein grp78 and hsp70 species but not constitutive hsc70 or
      hsp90. The kinetics of antibody production and reciprocal affinity purification
      experiments indicated that the grp78 and hsp70 responses were cross-reactive but
      distinct from immune responses to the primary Ro52 and Ro60 immunogens and the
      endoplasmic reticulum (ER)-resident chaperone calreticulin. No responses to
      molecular chaperones were detected in the La-immunized mice. Control
      immunizations indicated that the recruited grp78 and hsp70 responses were
      specific for the Ro proteins and not due to immunization with denatured protein.
      The rapid spreading of immunity to the inducible grp78 and hsp70 in Ro52- and
      Ro60-immunized mice suggests that these components may co-localize and physically
      associate under certain physiological conditions which may promote
      autoimmunization. The potential importance of the ER-resident chaperones grp78
      and calreticulin is further supported by their co-localization with Ro in small
      apoptotic membrane blebs and the finding of a novel putative grp78 binding motif
      in the carboxyl-terminal region of Ro52.

PMID- 9933453
TI  - Idiotype usage by polyclonally activated B cells in experimental autoimmunity and
      infection.
AB  - Both in animal models and in human systemic lupus erythematosus (SLE) the
      occurrence of nephritogenic autoantibodies bearing dominant idiotypes has been
      described. In this study we investigate the relation between the induction
      pathway of polyclonal B cell activation and the production and glomerular
      deposition of nephritogenic antibodies with shared dominant idiotype(s).
      Polyclonal B cell activation was induced in several experimental models
      characterized by glomerular immune deposit formation. We monitored the occurrence
      of dominant idiotypes among immunoglobulins deposited in the glomeruli. In
      addition, we studied the species specificity of the dominant idiotypes, by
      monitoring their presence in kidney sections of patients with an immunologically
      mediated kidney disease. Anti-idiotype antisera against two monoclonal anti-DNA
      autoantibodies were used, derived from MRL-lpr/lpr mice, i. e. clone H241 and
      clone H130. Autoantibodies with the H241 idiotype were present in immune complex
      depositions in all experimental models but not in humans. We therefore conclude
      that the presence of this dominant idiotype is independent of the induction
      pathway of polyclonal B cell activation. However, autoantibodies bearing the H130
      idiotype were only detected in kidney sections of mice with spontaneous lupus.

PMID- 9933454
TI  - A syndrome resembling human systemic sclerosis (scleroderma) in MRL/lpr mice
      lacking interferon-gamma (IFN-gamma) receptor (MRL/lprgammaR-/-).
AB  - MRL/lpr mice develop a systemic autoimmune disease characterized by
      autoantibodies and inflammatory lesions in various organs. The main cause of
      early mortality is glomerulonephritis. We previously found that MRL/lprgammaR-/-
      mice are protected from glomerulonephritis and have an increased life span
      compared with their MRL/lprgammaR+/+ littermates. We now carried out a
      histopathological study of a selection of organs of MRL/lprgammaR-/- mice. Mice
      were killed as soon as they showed clinical signs of disease. In the majority of
      animals skin lesions were the first apparent pathology. Mononuclear cell
      infiltrates were frequent in skin, lungs and kidneys, and they occurred also in
      liver, salivary glands and heart. In infiltrated areas there was an abnormal
      accumulation of bundles of collagen. In the lungs of MRL/lprgammaR-/- mice, and
      occasionally in other organs, small and middle-sized arteries and veins showed
      intimal proliferation, resulting in a narrowed lumen. Alveolitis was widespread.
      Mononuclear cell infiltrates and excessive production of collagen in the skin and
      several visceral organs, thickening of vascular intima and autoantibodies are
      characteristic features of human systemic sclerosis. Thus, MRL/lprgammaR-/- mice
      might represent a model for that disease.

PMID- 9933455
TI  - Cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      production by human retinal pigment epithelial cells.
AB  - GM-CSF is an important regulator of macrophage, granulocyte and dendritic cell
      behaviour and function. These cell types have been implicated in the retinal
      damage characteristic of endogenous posterior uveitis. Dendritic cells in the
      choroid have access to retinal antigens processed by the retinal pigment
      epithelial (RPE) cells of the blood-retinal barrier and are thought to be
      candidates for the presentation of antigen in uveoretinitis. We therefore
      investigated the production of GM-CSF and its regulation in human RPE cells. IL
      1beta, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor
      beta (TGF-beta) all stimulated GM-CSF production by RPE cells and a combination
      of these cytokines increased GM-CSF production over five-fold compared with that
      with the individual cytokines alone. Interferon-gamma (IFN-gamma) rapidly down
      regulated these responses. IFN-gamma did not appear to be acting directly on IL
      1beta or via the synthesis of another protein. GM-CSF mRNA expression showed the
      same pattern of response to these cytokines, indicating transcriptional or pre
      transcriptional regulation, and there was no evidence that IFN-gamma was acting
      by destabilizing GM-CSF mRNA. These results are generally important in
      understanding the ways in which cytokine regulation differs between different
      cell types and also more specifically for determining ways in which a cytokine
      with a significant role in the development of autoimmune uveoretinitis may be
      manipulated.

PMID- 9933456
TI  - Genetic markers in clinically well defined patients with ulcerative colitis (UC).
AB  - Results of genetic association studies in UC are conflicting. We propose that the
      power of candidate gene studies will increase when disease heterogeneity is taken
      into account. Phenotype frequencies of molecularly defined HLA-DR alleles,
      polymorphisms in the tumour necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha
      (LT-alpha), IL-1 receptor antagonist (IL-1Ra) and IL-1beta genes were determined
      in 98 clinically well characterized UC patients with a mean period of follow up
      of 10 years, and ethnically matched healthy controls (HC). The alleles HLA
      DRB1*0103 (phenotype frequency 6% versus 0.2%; P = 0.0002; odds ratio (OR) 27.6)
      and DRB1*15 (41% versus 26%; P = 0. 001; OR = 2.0, compared with HC) were
      associated with overall disease susceptibility. Subgroup analysis revealed that
      DRB1*15 was only increased in females (53% versus 24%; P < 0.0001; OR = 3.5), but
      not in males. With regard to disease localization, all DRB1*0103+ patients had
      extensive disease (P < 0.002; OR = 33.5), and DRB1*15 was found in 59% of females
      with extensive colitis (P < 0.0001; OR = 4.4). DRB1*0103 was significantly
      increased in patients undergoing colectomy (P < 0.0002; OR = 84). No association
      between overall disease susceptibility and the cytokine gene polymorphisms were
      found. Subgroup analysis revealed several significant associations, but most did
      not retain significance when corrected for multiple comparisons. However, a
      noticeable finding was that haplotype TNF-C was significantly associated with
      progression in extent of disease (P = 0.003, OR = 20.4). This study provides
      additional evidence for the role of DRB1 alleles in the susceptibility to UC, and
      supports the hypothesis that these alleles may determine the severity of the
      disease. The cytokine gene polymorphisms evaluated in this study do not seem to
      be strong risk factors for the overall disease susceptibility in UC, but may be
      involved in determining the severity of the disease.

PMID- 9933457
TI  - Interactions of allogeneic human mononuclear cells in the two-way mixed leucocyte
      culture (MLC): influence of cell numbers, subpopulations and cyclosporin.
AB  - With organ allografts considerable numbers of donor-type mononuclear cells are
      transferred to the recipient, leading to bilateral immunological interactions
      between donor and recipient lymphocytes. To study such bilateral immune reactions
      in detail, human two-way MLC were performed. In this model proliferation
      kinetics, patterns of activation, and survival of the two populations were
      analysed, and the relevance of initial cell subset composition, relative cell
      numbers, and the effect of immunosuppression on this co-culture were evaluated.
      It could be demonstrated that with an initial 50:50 ratio of two populations of
      allogeneic cells one population dominated after 21 days of co-culture in 78 out
      of 80 combinations (97%) tested; the other population decreased markedly after an
      initially stable phase of 6-7 days. With unequal starting conditions the larger
      population dominated when resting cells were used, but small populations of
      preactivated cells or separated CD8+ cells could also dominate. Depletion of
      CD16+ natural killer (NK) cells and of CD2- cells (B cell and monocytes) had no
      effect on domination. Addition of cyclosporin delayed or blocked the domination
      process while addition of IL-2 accelerated it. Disappearance of one population
      was associated with detection of apoptotic cells. The findings indicate that co
      cultures of allogeneic mononuclear cells are generally not stable for more than 1
      week, but lead to active elimination of one population. CD8+ cells and
      particularly preactivated cells seem to play the most important role in that
      process, while NK cells are of less importance. Cyclosporin can prolong survival
      of allogeneic cells in co-culture. These observations suggest that under the
      conditions of clinical organ transplantation even small amounts of
      immunocompetent donor cells transferred by the graft may persist for some time
      and may, thereby, have the chance to exert immunomodulatory functions.

PMID- 9933458
TI  - Mononuclear cell subpopulations in preterm and full-term neonates: independent
      effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal
      betamethason therapy, and mode of delivery.
AB  - Blood samples from 29 preterm (24-32 weeks of gestation) and 21 full-term (37-42
      weeks of gestation) neonates were analysed for surface markers of lymphocyte
      subtypes and macrophages, and the effects of gestational age, neonatal infection,
      maternal pre-eclampsia, maternal betamethason therapy and mode of delivery were
      assessed with multiple regression analysis. Gestational age alone had few
      independent effects (increase in CD3+, CD8+CD45RA+, and CD11alpha+ cells, and
      decrease in CD14+, HLA-DR- cells) during the third trimester on the proportions
      of the immune cell subtypes studied. Neonatal infection and mother's pre
      eclampsia had the broadest and very opposite kinds of effects on the profile of
      immune cells in the blood. Infection of the neonate increased the proportions of
      several 'immature' cells (CD11alpha-CD20+, CD40+CD19-, and CD14+HLA-DR-), whereas
      mother's pre-eclampsia decreased the proportions of naive cell types (CD4+CD8+,
      CD5+CD19+). In addition, neonatal infection increased the proportion of T cells
      (CD3+, CD3+CD25+, and CD4+/CD8+ ratio, and CD45RA+ cells), while maternal pre
      eclampsia had a decreasing effect on the proportion of CD4+ cells, CD4+/CD8+
      ratio, and proportions of CD11alpha+, CD14+ and CD14+HLA-DR+ cells. Maternal
      betamethason therapy increased the proportion of T cells (CD3+) and macrophages
      (CD14+, CD14+HLA-DR+), but decreased the proportion of natural killer (NK) cells.
      Caesarean section was associated with a decrease in the proportion of CD14+
      cells. We conclude that the 'normal range' of proportions of different
      mononuclear cells is wide during the last trimester; further, the effect of
      gestational age on these proportions is more limited than the effects of other
      neonatal and even maternal factors.

PMID- 9933459
TI  - Alterations in the number of circulating leucocytes, phenotype of monocyte and
      cytokine production in patients undergoing cardiothoracic surgery.
AB  - Changes in the differential blood cell count, monocyte phenotype and the cytokine
      plasma levels in a group of seven patients with cardiac surgery/cardiopulmonary
      bypass (CPB) and nine patients with thoracic surgery/without CPB, both receiving
      identical opioid-based anaesthetic technique, were assessed. A significant
      reduction in the number of circulating lymphocytes and monocytes was observed
      after anaesthesia and surgery. Interestingly, at the end of surgery as well as 1
      day post-surgery a marked increase in the number of granulocytes was noted.
      General anaesthesia and surgery caused a significant reduction of HLA-DR and
      CD11c/CD18 molecules, starting immediately after induction of anaesthesia, and an
      increase of CD64 at day 1 after anaesthesia. The use of a CPB was followed by a
      significant reduction of CD32, CD16, CD54 and HLA-ABC antigens expression at the
      end of surgery. One day after surgery these parameters returned nearly to
      baseline values with the exception of CD54. A monocyte subpopulation,
      characterized by low CD14, high CD16 and HLA-DR expression (CD14+CD16+HLA-DR++)
      was found in both groups at each time point, and the percentage of this cell
      subset decreased from baseline to 24 h. The plasma concentrations of IL-6 and IL
      10 increased considerably during CPB. No dynamic changes of IL-1 level due to
      surgery or CPB were found. We conclude that anaesthesia as well as the use of CPB
      induced profound alterations in the number of circulating leucocytes, and in the
      phenotype of monocyte and cytokine production.

PMID- 9933460
TI  - Apoptosis of Th1-like cells in experimental tuberculosis (TB).
AB  - Th1 cell-induced anti-mycobacterial immunity is lost during a progressive
      Mycobacterium tuberculosis infection in a susceptible host. This study was
      designed to test the mechanism of the loss of anti-mycobacterial cell-mediated
      immune response. We demonstrate that M. tuberculosis infection results in
      increased Fas expression and decreased Bcl-2 expression in CD4+ T cells. When
      CD4+ T cells are stimulated in vitro, they show increased apoptosis and decreased
      production of IL-2 and interferon-gamma (IFN-gamma) but not of IL-4. These
      changes may result in selective apoptosis of Th1-like cells, leading to the loss
      of cell-mediated immune response against M. tuberculosis.

PMID- 9933461
TI  - Role of peripheral blood mononuclear cell (PBMC) phenotype changes in the
      pathogenesis of haemorrhagic fever with renal syndrome (HFRS).
AB  - Hantaviruses cause an important human illness, HFRS. Blood samples from 22 HFRS
      positive, six seronegative patients and 15 healthy controls were examined in
      1995, during the largest HFRS epidemic in Croatia. Results of double- and triple
      colour immunofluorescence analysis showed an increased percentage of cytotoxic T
      cells (CD3+CD8+) in seropositive patients compared with seronegatives and healthy
      controls. The majority of seropositive HFRS patients expressed activation and
      memory antigens on T and B lymphocytes. The percentage of CD23+ and CD21+ B
      lymphocytes was lower in seropositive patients. HFRS patients had elevated levels
      of sCD23 and five had elevated total IgE. The increased expression of both early
      and late T cell activation antigens, e.g. CD25, CD71 and HLA-DR, memory cells and
      sCD23 positively correlated with biochemical parameters (AST, ALT, urea, alpha2
      globulin) during the acute phase of HFRS. The phenotypic changes observed,
      especially early and late T cell activation markers, as well as memory cells,
      could be useful parameters in the evaluation of HFRS course, and prognostic
      factors of HFRS severity. Additional attention should be paid to liver
      involvement in the pathogenesis of HFRS.

PMID- 9933462
TI  - Macrophage inflammatory protein-1alpha (MIP-1alpha) expression plasmid enhances
      DNA vaccine-induced immune response against HIV-1.
AB  - CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been
      identified as factors which suppress HIV. In this study we co-inoculated MIP
      1alpha expression plasmid with a DNA vaccine constructed from HIV-1 pCMV160IIIB
      and pcREV, and evaluated the effect of the adjuvant on HIV-specific immune
      responses following intramuscular and intranasal immunization. The levels of both
      cytotoxic T lymphocyte (CTL) activity and DTH showed that HIV-specific cell
      mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP
      1alpha expression plasmid with the DNA vaccine compared with inoculation of the
      DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly
      lowered when the plasmid was co-inoculated in both intramuscular and intranasal
      routes, suggesting a strong elicitation of the T helper (Th) 1-type response.
      When the MIP-1alpha expression plasmid was inoculated intramuscularly with the
      DNA vaccine, an infiltration of mononuclear cells was observed at the injection
      site. After intranasal administration, the level of mucosal secretory IgA
      antibody was markedly enhanced. These findings demonstrate that MIP-1alpha
      expression plasmid inoculated together with DNA vaccine acts as a strong adjuvant
      for eliciting Th1-derived immunity.

PMID- 9933463
TI  - Antigenicity of the Leishmania infantum histones H2B and H4 during canine
      viscerocutaneous leishmaniasis.
AB  - In this study we show that sera from dogs naturally infected with Leishmania
      infantum contain antibodies that specifically react against the parasite H2B and
      H4 histones. The Leishmania H2B and the amino-terminal region of the histone H4,
      expressed as fusion proteins, when confronted with sera from canine
      viscerocutaneous leishmaniasis (VCL) dogs, were recognized by 63% and 47%,
      respectively. No reactivity was detected when sera from dogs naturally infected
      with pathogens other than Leishmania were used. Using a collection of synthetic
      peptides covering the complete sequence of both proteins, we have determined that
      the main linear antigenic determinants are located in the amino-terminal domains
      of these histones. The humoral response against histones H2B and H4 induced
      during canine leishmaniasis was found to be specific for Leishmania histones,
      since no cross-reactivity of the VCL sera with mammal histones was observed.
      Also, a comparative study of the prevalence of antibodies among VCL sera against
      the four core histones of L. infantum was performed. Although a large
      heterogeneity of the humoral responses against these proteins was found, histones
      H2A and H3 seem to be more prevalent immunogens than histones H2B and H4 during
      canine natural leishmaniasis. The origin of the anti-histone humoral response and
      its possible implications in the pathogenesis of Leishmania infection are
      discussed.

PMID- 9933464
TI  - TNFalpha*2 marks high risk of severe disease during Plasmodium falciparum malaria
      and other infections in Sri Lankans.
AB  - We have investigated the association between alleles of the genes for tumour
      necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease during
      malarial (Plasmodium falciparum) and other infections in the Sri Lankan
      population. Patients were categorized as having either (i) uncomplicated malaria,
      (ii) severe and complicated malaria, or (iii) severe and complicated infection in
      which a diagnosis of malaria had been excluded. For all the patients, as well as
      for a group of matched healthy controls, TNF-alpha and TNF-beta allelic types
      were identified using the polymerase chain reaction (PCR) and allele-specific
      oligonucleotide probes and restriction enzyme digestion. The odds in favour of
      carrying the TNFalpha*2 allele, mainly of the heterozygous genotype
      (TNFalpha*1,*2), were two to three times greater among individuals with severe
      disease, of either malarial or other infectious origin, relative to healthy
      controls or to those with uncomplicated malarial infections. No significant risk
      was associated with either of the alleles of TNF-beta.

PMID- 9933465
TI  - A novel mutant gammac chain from a patient with typical phenotype of X-linked
      severe combined immunodeficiency (SCID) has partial signalling function for
      mediating IL-2 and IL-4 receptor action.
AB  - Mutations of the common gamma (gammac) chain result in X-linked SCID (X-SCID),
      which is characterized by the reduction in number or absence of peripheral blood
      T cells and natural killer (NK) cells, with retention of normal numbers of B
      cells. In the present study we describe a novel mutant gammac chain of an X-SCID
      patient with a typical X-SCID phenotype. This mutant receptor subunit is able to
      associate with Jak3 to transduce a weak signal. The Jak3-specific action is
      demonstrated by the induction of gene expression through the haematopoietin
      receptor response element (HRRE) by IL-2 and IL-4 in the experimental model of
      transiently transfected hepatoma cells over-expressing Jak3. This result suggests
      that a threshold in the gammac-Jak3 interaction determines the X-SCID phenotype.

PMID- 9933466
TI  - Anti-proteinase-3 (PR3) antibodies (C-ANCA) recognize various targets on the
      human umbilical vein endothelial cell (HUVEC) membrane.
AB  - Numerous studies suggest that C-ANCA are directly pathogenic in vasculitis by
      activating leucocytes (oxidative burst, enzyme release, endothelial cytotoxicity,
      etc.). We and others have shown that C-ANCA can also directly activate HUVEC, but
      the precise target on HUVEC is unknown. We show in this study that C-ANCA
      recognize various targets on the HUVEC membrane (different from PR3 in our
      model), leading to secondary cell activation. Polyclonal affinity-purified C-ANCA
      recognized targets on the unfixed endothelial membrane in fluorescent ELISA, flow
      cytometry, and immunoprecipitation studies. C-ANCA did not react with Fcgamma
      receptors. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments
      showed that HUVEC did not express PR3. The targets of polyclonal and monoclonal
      anti-PR3 antibodies on the endothelial membrane were not the same. Some epitopes
      were lost after trypsin-EDTA digestion and formaldehyde fixation of cells,
      whereas anti-PR3 targeted unfixed HUVEC. This suggests that anti-PR3 react with
      the endothelial membrane and recognize conformational epitopes shared with PR3.
      Endothelial cells may thus participate in the inflammation associated with
      Wegener's granulomatosis and contribute to the emergence of clinical
      manifestations.

PMID- 9933467
TI  - A comparison of the characteristics of circulating anti-myeloperoxidase
      autoantibodies in vasculitis with those in non-vasculitic conditions.
AB  - Although circulating anti-neutrophil cytoplasmic antibodies (ANCA) specific for
      myeloperoxidase (MPO) are strongly associated with the presence of vasculitis,
      they have been described in sera from patients with other conditions. High levels
      of anti-MPO antibodies can also persist in sera from patients with vasculitis
      despite the achievement of clinical remission. One possible interpretation is
      that a potentially pathogenic subset of anti-MPO antibodies exists, which is only
      present in patients with active vasculitis. We therefore compared the
      characteristics of anti-MPO antibodies in sera from patients with active
      vasculitis (n = 18) with those present in remission (n = 9) and in a disease
      control group (n = 10) without clinical evidence of vasculitis. The class,
      subclass and ability of anti-MPO antibodies from the three groups of patients to
      recognize three different conformational epitopes were analysed using ELISA-based
      techniques. The expression of an idiotope, designated 9G4, was also examined.
      Epitope recognition by anti-MPO antibodies from all patients tested was found to
      be similar. Sera from patients with active vasculitis showed an over
      representation of IgG4 subclass anti-MPO antibodies and a more frequent presence
      of IgM class anti-MPO antibodies. In disease controls, IgG1 anti-MPO antibodies
      were predominant. In vitro, neutrophil activation by ANCA has been shown to be
      dependent on engagement of neutrophil FcgammaRIIa receptors following binding of
      these autoantibodies to surface-expressed ANCA antigens. We found that active
      vasculitis may be associated with the presence of circulating anti-MPO antibodies
      which do not significantly bind this receptor, suggesting that mechanisms other
      than those dependent on FcgammaRIIa binding should be explored. In addition, the
      expression of the 9G4 idiotope on anti-MPO antibodies in 60% (12/18) of patients
      with active vasculitis and 20% (2/10) of disease control patients may indicate a
      common origin for anti-MPO antibodies in different individuals.

PMID- 9933468
TI  - Comparison of recombinant human PTH(1-34) (LY333334) with a C-terminally
      substituted analog of human PTH-related protein(1-34) (RS-66271): In vitro
      activity and in vivo pharmacological effects in rats.
AB  - Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are believed to exert
      their biological actions through binding and activation of a common cell surface
      receptor. Recently, an analog of PTHrP (RS-66271), was described that
      demonstrated reduced binding affinity for the PTH/PTHrP receptor compared with
      bovine PTH(1-34) but retained equal biological activity. The present study
      investigated the receptor binding affinities of synthetic RS-66271 and
      recombinant human PTH(1-34) (LY333334) and compared their in vitro and in vivo
      pharmacological effects. RS-66271 had one hundredth the activity of PTH(1-34) in
      competing for the binding of [125I] [Nle8,18, Tyr34]human PTH(1-34) to the human
      PTH/PTHrP receptor stably expressed in a human kidney cell line. Despite this
      reduced binding affinity, RS-66271 had equivalent activity in increasing both
      cAMP production in osteoblast-like cells and bone resorption in neonatal mouse
      calvariae. However, RS-66271 was 7. 6-fold less active in stimulating inositol
      phosphate production. For in vivo studies, young, male Fisher rats received a
      daily subcutaneous dose of either 10 or 40 microg/kg of peptide for 1, 2, or 4
      weeks. Volumetric bone mineral density and total bone mineral content of the
      proximal tibia were determined by peripheral quantitative computerized
      tomography. Trabecular and cortical bone of the distal femur were analyzed for
      calcium and dry weight. Lumbar vertebrae (L4-L6) were analyzed by
      histomorphometry. Trabecular and cortical bone mass showed a dose- and time
      dependent increase in the treated animals compared with the controls. These
      increases were evident as early as 1 week after initiation of dosing. There were
      no consistent significant differences in the comparative effects of PTH(1-34) and
      RS-66271 on the measured bone parameters. In conclusion, despite the reduced
      binding affinity of RS-66271 for the PTH/PTHrP receptor compared with human PTH(1
      34), both peptides displayed similar in vitro and in vivo pharmacological
      effects.

PMID- 9933469
TI  - Interactions of PTH and PTHrP with the PTH/PTHrP receptor and with downstream
      signaling pathways: exceptions that provide the rules.

PMID- 9933470
TI  - High-dose estrogen induces de novo medullary bone formation in female mice.
AB  - It is well recognized that, in the mouse, high-dose estrogen induces sclerosis
      within the shaft of long bones, an action that is largely thought to reflect
      increased osteoblastic cellular activity. We undertook to characterize this
      response in more detail, by performing a histologic analysis of the early changes
      induced by high-dose estrogen in the tibial cavity of young intact female mice.
      Female mice were sacrificed immediately before or 4, 8, 12, or 24 days after
      commencing subcutaneous injections of 17beta-estradiol (500 microg/animal/week),
      and longitudinal tibial sections were subsequently examined. Estrogen was found
      to cause a rapid gain in cancellous bone, with cancellous bone volume increasing
      by approximately 50% after 8 days, and by 5-fold after 24 days. Analysis of
      cancellous double-labeled surfaces revealed that this gain in bone reflected the
      emergence of new cancellous bone formation sites within the medullary cavity,
      rather than the reactivation and extension of formation over pre-existing bone
      surfaces. Comparison of the time course of these changes between proximal and
      distal regions of the proximal tibial metaphysis suggested that these new
      cancellous formation sites appear as a rapid wave extending distally from the
      secondary spongiosa. Alkaline phosphatase (ALP) immunocytochemistry revealed
      that, by 12 days after estrogen administration, a population of strongly ALP
      positive cells had appeared throughout the marrow cavity. We conclude that, at
      the proximal tibial metaphysis of female mice, estrogen-induced medullary
      sclerosis largely reflects a process of de novo medullary bone formation,
      possibly mediated by the generation of osteoblasts from bone marrow
      osteoprogenitor cells.

PMID- 9933471
TI  - Mice, estrogen, and postmenopausal osteoporosis.

PMID- 9933472
TI  - The epidemiology of Paget's disease in Britain: is the prevalence decreasing?
AB  - To estimate changes in the age- and gender-specific prevalence of Paget's disease
      in Britain, we performed a radiographic survey of the disorder in 10 British
      centers, using sampling and radiographic methods identical to a study performed
      in 1974. In each center, a sample of abdominal radiographs of people aged 55
      years and over was taken from stored films within the radiology department of the
      principal general hospital. The radiographs were identified by screening
      radiographic records over the period 1993-1995. Any abdominal radiograph in a
      subject aged 55 years and over which included the entire pelvis, sacrum, femoral
      heads, and all lumbar vertebrae was studied. The radiographs were evaluated by a
      trained observer and the consultant radiologist who participated in the original
      1974 survey. Nine thousand eight hundred and twenty-eight radiographs (4625 men,
      5203 women) were assessed in the 10 towns. The overall age/gender standardized
      prevalence rate was 2%, with a male/female ratio of 1.6. Prevalence increased
      steeply with age among men and women, rising to 6.9% of men and 5.8% of women
      aged 85 years and over. The prevalence of Paget's disease in the 10 towns in 1994
      was only 40% of that observed during the 1974 study. The decline in prevalence
      was apparent in all 10 centers, but was most marked in those with high rates in
      the original study. This survey of Paget's disease in 10 British towns suggests a
      prevalence of 2.5% among men and 1.6% among women aged 55 years and over. Age
      adjusted prevalence rates declined steeply between 1974 and 1994. These declines
      suggest an environmental contribution to the etiology of this disorder that
      requires further investigation.

PMID- 9933473
TI  - Recurrence of vertebral fracture with cyclical etidronate therapy in
      osteoporosis: histomorphometry and X-Ray microanalysis evaluation.
AB  - In an open prospective study, we evaluated differences between patients with
      (wRVF group) and without recurrence of vertebral fracture (woRVF group) during
      cyclical etidronate therapy for osteoporosis. Thirty-two patients (age 64 +/- 1.8
      years) characterized by at least one osteoporotic VF were treated during 1 year.
      At baseline, body mass index was significantly lower (23.3 +/- 0.6 vs. 26.9 +/-
      1.0 kg/m2, p< 0.05), the number of previous VFs was higher (4.0 +/- 0. 4 vs. 2.4
      +/- 0.4, NS), and patients were older in the wRVF group as compared with the
      woRVF group (67.8 +/- 3 vs. 62.6+/- 2.2 year, NS). Trabecular bone volume (11.6
      +/- 1.2 vs. 15 +/- 0.9%, p< 0.05) and trabecular number (1.06 +/- 0.08 vs. 1.27
      +/- 0.05, p < 0.05) were significantly lower in the wRVF group. None of the
      baseline resorptive variables differed, whereas the bone formation rate (BFR) was
      2-fold lower in the wRVF group (p< 0. 05). After 1 year of treatment, osteoclast
      number, active eroded surfaces, and resorption depth dramatically decreased in
      both groups (p< 0. 01). To a lesser extent, the mineral apposition rate and serum
      alkaline phosphatase level were significantly reduced (p< 0.05). No impaired
      mineralization was observed. Using X-ray microanalysis, we found no abnormality
      in bone mineral but a significant increase of the calcium/phosphorus ratio during
      treatment in the wRVF group. Our results demonstrate that recurrence of VFs
      within the first year of cyclical etidronate therapy was related neither to a
      lack of histologic response to the treatment nor induction of an abnormality of
      mineralization. VFs were more likely in the presence of a decreased BFR and lower
      trabecular connectivity, providing support for treating osteoporotic patients
      with etidronate early in the course of the disease.

PMID- 9933474
TI  - Early estrogen replacement therapy reverses the rapid loss of trabecular bone
      volume and prevents further deterioration of connectivity in the rat.
AB  - To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes
      in trabecular bone volume (BV/TV) and connectivity beginning either at
      ovariectomy (OVX) or 5-13 days after OVX in adult female rats, the right proximal
      tibial was examined by three-dimensional X-ray tomographic microscopy (XTM) in
      vivo. Animals had XTM scans of the right tibia and then were randomized into six
      groups (n = 9). Groups 2-6 had bilateral (OVX), while group 1 was sham
      ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and
      2) or 17beta-estradiol therapy (ERT) at 10 microg/kg three times per week
      starting at days 0, 5, 8, and 13 post-OVX (groups 3, 4, 5, and 6), until day 50
      when they were rescanned by XTM and sacrificed. Trabecular bone structural
      variables were calculated from XTM data (BV/TVx and beta1/BV/TVx) and standard
      histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections
      per cubic millimeter of trabecular bone (beta1/BV/TVx) were maintained in both
      sham-OVXd animals and OVX animals given ERT from the time of OVX. However, OVX +
      vehicle-treated animals lost 54% BV/TVx and 46% beta1/BV/TVx (p < 0. 01 from day
      0). BV/TVx and beta1/BV/TVx decreased rapidly post-OVX to -22% and -25% at day 13
      (p < 0.01 from day 0). ERT initiated at day 5, 8, and 13 post-OVX restored BV/TVx
      to baseline values at day 50 by modestly increasing trabecular plate thickness;
      however, beta1/BV/TVx was reduced in all OVX groups when compared with their
      baseline values. ERT also caused a significant reduction in bone turnover
      compared with OVX + vehicle; however, resorption was suppressed more than
      formation. These results demonstrate that ERT can restore the lost trabecular
      bone, but not trabecular connectivity, that occurs soon after OVX by allowing
      bone formation to continue in previously activated bone remodeling units while
      suppressing the production of new remodeling units. This may be the mechanism by
      which prompt intervention with estrogen and other antiresorptive agents can
      restore bone mass that has been lost from the increase in remodeling space, and
      thereby reduce the risk of osteoporotic fractures in postmenopausal women.

PMID- 9933475
TI  - Smoking increases bone loss and decreases intestinal calcium absorption.
AB  - Cigarette use is a risk factor for increased bone mineral density (BMD) loss but
      the mechanisms are not well understood. The relationship of smoking to rates of
      BMD change at the femoral neck, spine, and total body, and to intestinal calcium
      absorption were examined in 402 elderly men and women (32 smokers, 370
      nonsmokers) who participated in a 3-year placebo-controlled study of calcium and
      vitamin D supplementation. Subjects in the supplemented group took 500 mg/day of
      elemental calcium and 700 IU/day of cholecalciferol. Two-hour calcium absorption
      fraction was determined three times, at 18, 30, and 36 months, with a single
      isotope method utilizing 45Ca in a subset of 333 subjects. Annualized rates of
      BMD loss (adjusted for baseline BMD, weight, age, gender, supplementation status,
      and dietary calcium intake) were higher in smokers than nonsmokers at the femoral
      neck (-0.714 +/- 0.285 %/year vs. +0.038 +/- 0.084 %/year, p < 0.02), and total
      body (-0.360 +/- 0.101 %/year vs. -0. 152 +/- 0.030 %/year, p < 0.05). No
      significant difference was observed at the spine (+0.260 +/- 0.252 %/year in
      smokers vs. +0.593 +/- 0.074 %/year in nonsmokers, p = 0.21). The mean (+/- SEM)
      calcium absorption fraction was lower in smokers (12.9 +/- 0.8%, n = 23) than
      nonsmokers (14.6 +/- 0.2%, n = 310, p < 0.05) after adjustment for gender, age,
      supplementation status, and dietary calcium and vitamin D intakes. Smokers of at
      least 20 cigarettes per day (n = 15) had the lowest mean absorption fraction
      (12.1 +/- 1.1%). With calcium and vitamin D supplementation, the proportionate
      increase in urinary calcium/creatinine excretion was lower in smokers (44 +/-
      12%) than nonsmokers (79 +/- 9%, p < 0.05). These results suggest that smoking
      accelerates bone loss from the femoral neck and total body in the elderly and
      that less efficient calcium absorption may be one contributing factor.

PMID- 9933476
TI  - Altered expression of bone sialoproteins in vitamin D-deficient rBSP2.7Luc
      transgenic mice.
AB  - Bone sialoprotein (BSP) and osteopontin (OPN) are two major noncollagenous matrix
      proteins in mineralized connective tissue that have discrete roles in bone matrix
      formation, mineralization, and remodeling. The osteotropic secosteroid, 1,25
      dihydroxyvitamin D3, a potent regulator of bone remodeling required for normal
      bone development, has been shown to exert differential effects on OPN and BSP
      expression by bone cells in vitro. To investigate these effects in vivo, we
      induced vitamin D3 deficiency in a transgenic mouse line (rBSP2.7Luc) that has a
      2.7 kb rat BSP promoter linked to a luciferase reporter gene in its genome.
      Pregnant rBSP2.7Luc mice were fed vitamin D3-deficient food and demineralized
      water for 6 weeks. Their offspring were weaned at 3 weeks of age and then fed
      vitamin D-deficient food for an additional week. The control group were fed
      normal rodent pellets and water during the entire experimental procedure. Bone
      tissues from 40, 4-week-old offspring in each group were analyzed for BSP, OPN
      and luciferase expression. Vitamin D3-deficient mice displayed a rachitic
      phenotype that included reduced size and malformation of bones. Assays of the BSP
      promoter transgene in calvariae, mandibles, and tibiae of the rachitic mice
      showed increases in luciferase activity of 3.1-, 1.9-, and 4.6-fold,
      respectively, when compared with control littermates. Semiquantitative reverse
      transcriptase polymerase chain reaction assays of BSP mRNA revealed increases of
      7-, 74-, and 66-fold, respectively, in the same rachitic bones, while OPN mRNA
      was reduced 12.5-fold in calvariae and 2-fold in tibiae and mandibles. In situ
      hybridization using mouse cRNA probes revealed that the increased BSP expression
      and decreased OPN expression in the vitamin D3-deficient mice was primarily in
      osteoblastic cells on the surface of calvariae and endosteal spaces of alveolar
      bone, on newly formed epiphyseal bone, and in cementoblasts and in hypertrophic
      chondrocytes. These studies are the first to show that BSP and OPN are
      differentially regulated by vitamin D3 in vivo, reflecting the diverse roles of
      these protein in bone remodeling. Moreover, the increased expression of the BSP
      transgene in the rachitic mice demonstrates that vitamin D3 regulation of BSP
      expression is mediated, in part, by element(s) within the 2.7 kb promoter region.

PMID- 9933477
TI  - Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese
      kindred to chromosome 1q22-q31.
AB  - A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism
      (HPT) that was associated with parathyroid adenomas and carcinomas was
      investigated with the aim of determining the chromosomal location of this gene,
      designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7
      parathyroid tumors from 4 patients was used in comparative genomic hybridization
      (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH
      studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH
      studies were consistent with the involvements of tumor suppressor genes from
      these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31
      by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428,
      D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0%
      recombination), and defined the location of HPT Port to a 21 cM region flanked
      centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been
      mapped to chromosome 1q22-q31, and a characterization of this gene will help to
      elucidate further the mechanisms that are involved in the development of
      parathyroid tumors.

PMID- 9933478
TI  - The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene
      expression in the small intestine.
AB  - The actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are mediated through the
      nuclear vitamin D receptor (VDR). The regulation of VDR abundance plays an
      important role in determining the magnitude of the target cell response to
      1,25(OH)2D3. The major physiological activity of 1,25(OH)2D3 is the regulation of
      calcium absorption in the small intestine, and the level of VDR is an important
      factor in this regulation. However, the characterization of VDR gene expression
      in the small intestine remains unknown. In the present study, we investigated the
      regulation of the human VDR (hVDR) gene expression in the small intestine. The
      4.0 kb of the 5'-flanking region of the hVDR gene promoter was cloned and
      characterized by the measurement of luciferase activity and an electrophoretic
      mobility-shift assay (EMSA). With the EMSA, we found that Cdx-2 (a homeodomain
      protein-related caudal) binds to the sequence 5'-ATAAAAACTTAT-3' at -3731 to 
      3720 bp (hVD-SIF1) relative to the transcription start site of the hVDR promoter.
      This sequence is very similar to the human sucrase-isomaltase footprint 1 (SIF1)
      element. With a competition analysis and specific antibodies for Cdx-2, we
      demonstrated that Cdx-2 is able to activate VDR gene transcription by binding to
      this element. The mutation of the hVD-SIF1 sequence in the hVDR gene promoter
      markedly suppressed the transactivation of the reporter gene in Caco-2 cells. In
      addition, the DNA fragment (-3996 to -3286) containing the hVD-SIF1 binding site
      increased transcription when placed upstream of the herpes simplex virus
      thymidine kinase promoter. These findings suggest that Cdx-2 plays an important
      role in the intestine-specific transcription of the hVDR gene.

PMID- 9933479
TI  - A trans-acting enhancer modulates estrogen-mediated transcription of reporter
      genes in osteoblasts.
AB  - The presence of bone-specific estrogen agonists and discovery of the osteoblast
      specific transcription factor (TF), Cbfa1, together with the discovery of
      synergism between a TF Pit-1 and estrogen receptor alpha (ERalpha) on rat
      prolactin gene, led to investigation of Cbfa1 in the modulation of osteoblast
      specific actions of estrogen. Reverse transcribed-polymerase chain reaction
      demonstrated expression of Cbfa1 in the osteoblastic cell lines, MG63, ROS17/2.8,
      and MC3T3E1, but not in nonosteoblastic cell lines, MCF7, C3H10T1/2, and HeLa. An
      ER expression vector and a series of luciferase (Luc) reporter plasmids harboring
      the Cbfa1 binding site OSE2 (the osteoblast-specific cis element in the
      osteocalcin promoter) and palindromic estrogen response elements (EREs) were
      cotransfected into both osteoblastic and nonosteoblastic cells. OSE2 worked as a
      cis- acting element in osteoblastic cells but not nonosteoblastic cells, whereas
      EREs were cis- acting in all cell lines. Synergistic transactivation was observed
      in osteoblastic cells only when both ERE and OSE2 were placed in juxtaposition to
      the promoter. Forced expression of Cbfa1 in C3H10T1/2 cells also induced
      synergism. Tamoxifen, a partial agonist/antagonist of estrogen, acted as an
      osteoblast-specific agonist in cells transfected with a promoter containing ERE
      and acted synergistically with a promoter containing the ERE-OSE2 enhancer
      combination. These results support the idea that bone-specific TFs modulate the
      actions of estrogen in a tissue-specific manner.

PMID- 9933480
TI  - Marked osteoblastopenia and reduced bone formation in a model of multiple myeloma
      bone disease in severe combined immunodeficiency mice.
AB  - We report on an in vivo model of human myeloma producing bone disease in
      irradiated severe combined immunodeficiency disease mice using the human myeloma
      cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstein-Barr
      virus transformed and produce large amounts of hepatocyte growth factor (HGF).
      Mice had radiological signs of osteolysis and mild hypercalcemia. Xenografted
      cells were predominantly found in bone marrow and brown adipose tissue, but also
      in meninges and liver. Take was documented by histopathological examination,
      immunophenotyping of cultured bone marrow, and radiography. HGF was detected in
      serum and bone marrow plasma. Disease generally occurred within 45 days of
      intravenous inoculation and was signaled by paraparesis or signs of intracranial
      neoplasia. More than 90% of the mice had take of xenografts. The subline JJN-3 T1
      gave more reproducible bone marrow take than the native cell line. Bone
      histomorphometric examination revealed a 99% reduction in osteoblast counts and a
      33% reduction in osteoclast counts in areas of tumor growth. Bone formation rates
      were reduced by 53%. The results suggest that osteoblastopenia and reduced bone
      formation is of importance for the occurrence of osteolytic lesions in this
      model.

PMID- 9933481
TI  - The material basis for reduced mechanical properties in oim mice bones.
AB  - Osteogenesis imperfecta (OI), a heritable disease caused by molecular defects in
      type I collagen, is characterized by skeletal deformities and brittle bones. The
      heterozygous and homozygous oim mice (oim/+ and oim/oim) exhibit mild and severe
      OI phenotypes, respectively, serving as controlled animal models of this disease.
      In the current study, bone geometry, mechanics, and material properties of 1-year
      old mice were evaluated to determine factors that influence the severity of
      phenotype in OI. The oim/oim mice exhibited significantly smaller body size,
      femur length, and moment of area compared with oim/+ and wild-type (+/+)
      controls. The oim/oim femur mechanical properties of failure torque and stiffness
      were 40% and 30%, respectively, of the +/+ values, and 53% and 36% of the oim/+
      values. Collagen content was reduced by 20% in the oim/oim compared with +/+ bone
      and tended to be intermediate to these values for the oim/+. Mineral content was
      not significantly different between the oim/oim and +/+ bones. However, the
      oim/oim ash content was significantly reduced compared with that of the oim/+.
      Mineral carbonate content was reduced by 23% in the oim/oim bone compared with
      controls. Mineral crystallinity was reduced in the oim/oim and oim/+ bone
      compared with controls. Overall, for the majority of parameters examined
      (geometrical, mechanical, and material), the oim/+ values were intermediate to
      those of the oim/oim and +/+, a finding that parallels the phenotypes of the
      mice. This provides evidence that specific material properties, such as mineral
      crystallinity and collagen content, are indicative and possibly predictive of
      bone fragility in this mouse model, and by analogy in human OI.

PMID- 9933482
TI  - The primary calcification in bones follows removal of decorin and fusion of
      collagen fibrils.
AB  - To elucidate the mechanisms of primary calcification in bone, ultrastructural
      changes in collagen fibrils, as well as cytochemical alteration of proteoglycan,
      especially decorin, were investigated morphologically in 19-day postcoitum
      embryonic rat calvariae. Below the osteoblast layer, calcification of the osteoid
      area increased in direct proportion to its distance from the osteoblasts. In the
      uncalcified osteoid area, collagen fibrils near matrix vesicles possessed sharp
      contours and were a uniform 50 nm in diameter. Immunoelectron microscopy revealed
      decorin to be abundantly localized in the vicinity of the collagen fibrils. In
      the osteoid area undergoing the process of calcification, collagen fibrils tended
      to fuse side by side. Where calcification was progressed, this fusion was even
      more so. Some very large fibrils exhibited complicated contours, 400 nm or more
      in diameter. Although the calcification at this stage affected areas both inside
      and outside of the collagen fibrils, the interior areas manifested a lower
      density of calcification. The immunolocalization of decorin was also much
      decreased around these fibrils. Thus, primary calcification in bone matrix
      follows the removal of decorin and fusion of collagen fibrils. This phenomenon
      may aid in the process of calcification and bone formation, because (1)
      inhibitors of calcification, such as decorin, are removed, (2) the fusion of
      collagen fibrils provides the room necessary for rapid growth of mineral
      crystals, and (3) the soft elastic bone matrix containing abundant fused collagen
      fibrils less subjective to calcification is safe for both maternal and embryonic
      bodies and is convenient for subsequent bone remodeling.

PMID- 9933483
TI  - Mechanism of bone loss after liver transplantation: A histomorphometric analysis.
AB  - Organ transplantation is associated with increased bone loss and high fracture
      risk, but the pathophysiological mechanisms responsible have not been
      established. We have performed a histomorphometric analysis of bone remodeling
      before and 3 months after liver transplantation in 21 patients (14 male, 7
      female) aged 38-68 years with chronic liver disease. Eight-micrometer
      undecalcified sections of trans-iliac biopsies were assessed using image
      analysis. Preoperatively, bone turnover was low with a tendency toward reduced
      wall width and erosion depth. The bone formation rate increased from 0.021 +/-
      0.016 (mean +/- SD) to 0.067 +/- 0.055 microm2/microm/day after transplantation
      (p < 0.0002) and activation frequency from 0.24 +/- 0.21/year-1 to 0.81 +/- 0.
      67/year-1 (p < 0.0001). No significant change was observed in wall width, but
      there was a trend toward an increase in indices of resorption cavity size. There
      was a small increase in osteoid seam width postoperatively (p< 0.02) and decrease
      in mineralization lag time (p < 0.001). No significant changes in indices of
      cancellous bone structure were observed in the postoperative biopsies. These
      results demonstrate a highly significant and quantitatively large increase in
      bone turnover in the first 3 months after liver transplantation. Although no
      significant disruption of cancellous bone structure was demonstrated during the
      time course of the study, the observed changes in bone remodeling predispose to
      trabecular penetration and may thus result in long-term adverse effects on bone
      strength.

PMID- 9933484
TI  - Expression of gelatinase A and its activator MT1-MMP in the inflammatory
      periprosthetic response to polyethylene.
AB  - Wear debris of polyethylene prosthetic components is known to induce a host
      granulomatous reaction which recruits numerous macrophages and multinucleated
      giant cells. By releasing cellular mediators of a nonspecific inflammatory
      reaction, activated phagocytic cells are thought to play a key role in osteolysis
      leading to aseptic loosening of the prosthesis. Matrix metalloproteinases (MMPs)
      have been implicated in this destructive process by their ability to degrade
      extracellular matrix components of bone and adjacent connective tissue. To
      investigate the roles of gelatinase A, its activator MT1-MMP, and the MMP
      inhibitors TIMP-1 and TIMP-2 in aseptic loosening of polyethylene prostheses,
      immunohistochemistry (IHC) and in situ hybridization (ISH) were performed on
      periprosthetic pseudosynovial interface tissues. Gelatinase A and MT1-MMP were
      strongly detected immunohistochemically in macrophages and multinucleated giant
      cells in contact with polyethylene wear debris. In contrast to MT1-MMP,
      gelatinase A mRNAs were not found in phagocytic cells but in surrounding
      fibroblasts, thereby suggesting cooperation between macrophages and fibroblasts
      in this process. While TIMP-1 was expressed essentially in hyperplastic
      pseudosynoviocytes as assessed by IHC and ISH, TIMP-2, MT1-MMP, and gelatinase A
      were colocalized in phagocytic cells. These data support the concept of
      progelatinase A activation involving a trimolecular complex (MT1-MMP-TIMP-2
      gelatinase A) mechanism. Thus, this study demonstrated that gelatinase A and its
      activator might contribute to the aseptic loosening of polyethylene prostheses.

PMID- 9933485
TI  - Magnesium deficiency and bone loss after cardiac transplantation.
AB  - Magnesium depletion adversely affects many phases of skeletal metabolism and has
      been implicated as a risk factor in several forms of osteoporosis. Magnesium
      deficiency has also been reported after cardiac transplantation. To evaluate
      whether altered magnesium homeostasis could be related to the pathogenesis of
      early bone loss after cardiac transplantation, we prospectively measured serum
      and urinary magnesium and evaluated them with respect to biochemical indices of
      mineral metabolism and rates of bone loss. The study population included 60
      patients (45 men, 15 women) aged 53 +/- 11 years (SD) with measurements of
      biochemistries and bone mineral density by dual-energy X-ray absorptiometry
      before and 3 months after transplantation. All received prednisone, cyclosporine
      A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After
      transplantation, serum magnesium decreased by 16 +/- 15% (SD) from 2. 0 +/- 0.3
      mg/dl to 1.6 +/- 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0. 0001), accompanied by an
      increase in the fractional excretion of magnesium (7.1 +/- 3.9% to 13.3 +/- 5.6%;
      p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (</=
      1.7 mg/dl) sustained 41% less bone loss at the lumbar spine (4.0 +/- 4.6% vs. 6.
      8 +/- 5.3%; p = 0.051) and 58% less bone loss at the femoral neck (3. 1 +/- 5.9%
      vs. 7.3 +/- 5.6%; p < 0.01), despite receiving similar doses of prednisone and
      cyclosporine A. Of the biochemical parameters measured (including renal function,
      serum calcium, phosphorus, vitamin D metabolites, osteocalcin, urinary calcium,
      and markers of bone resorption), only intact parathyroid hormone (PTH) levels,
      which were 40% lower in patients with low serum magnesium levels differed
      significantly (45 +/- 23 pg/ml vs. 74 +/- 60 pg/ml; p = 0.019). Patients with low
      serum magnesium levels also had evidence of lower bone turnover. In summary, a
      highly significant decline in serum magnesium concentrations, associated with
      continued urinary magnesium losses, occurs after cardiac transplantation.
      Patients with low serum magnesium levels had significantly lower rates of bone
      loss, lower serum PTH concentrations, and lower bone turnover. Although the
      precise mechanisms by which the reduction in serum magnesium tends to protect
      against bone loss in the early post-transplantation period remain to be
      elucidated, reduced serum PTH and lower rates of bone turnover are likely to be
      important factors.

PMID- 9933486
TI  - Preparation of a cDNA library and preliminary assessment of 1400 genes from mouse
      growth cartilage.
AB  - Cartilage is an inconvenient tissue for the isolation of mRNA, and this has
      hampered studies of its component mRNAs conducted to date. Here, we describe the
      preparation of a good quality cDNA library from mouse growth cartilage (mGC). A
      total of 1.7 microg of poly(A)+ RNA was obtained from about 1200 pieces of the
      mGC zone of 60 young mice (BALB/c, 4 weeks old). Using this poly(A)+ RNA, we
      constructed a cDNA library using the pAP3neo vector by the linker-primer method.
      The complexity of the cDNA library was 2.6 x 106 colony-forming units (cfu),
      which signified that almost all of the mRNA components in the mGC were present in
      this cDNA library. From this library, 1401 clones were randomly selected and
      their insert sizes were examined. Of these clones, 166 (12%) had no inserts, 466
      (33%) had inserts ranging in size from 0-0.9 kbp, 480 (34%) had inserts of 1. 0
      1.9 kbp, 162 (12%) had inserts of 2.0-2.9 kbp, and 127 (9%) had sizes greater
      than 3.0 kbp. The average insert size was 1.45 kbp. The number of cfu and the
      insert size data qualified this library as of reasonably good quality. Clones
      with an insert size greater than 1 kbp (769 clones) were sequenced from their 5'
      ends. Among the 769 clones examined, 608 gave sequence data. Among these, 196
      (32%) were unknown, 2 were only poly A, and 410 (67%) coded for known proteins.
      Of these, 55 clones coded for type II (pro)collagen, 54 for osteonectin, and 22
      for other cartilage collagens (type IX, type X, and type XI). The rest included
      cartilage extracellular matrix genes, general cellular genes, and others. To
      judge further the quality of the library, 45 species coding for type II collagen
      chain were aligned based on their 5' end sequences. Three species (7%) contained
      almost the full-length insert, and the shortest one was 1. 5 kbp in length (full
      length 5.6 kbp). These data show that this cDNA library is of reasonably good
      quality, making it likely that the large number of unknown inserts (32%) will
      provide a suitable pool for the identification and functional determination of
      new GC genes.

PMID- 9933487
TI  - Tartrate-resistant acid phosphatase forms complexes with alpha2-macroglobulin in
      serum.
AB  - Tartrate-resistant acid phosphatase (TRAP) is a standard histochemical marker of
      differentiated osteoclasts and has been proposed as a serum/plasma marker for
      osteoclast activity. Enzyme assays have been described that show elevated TRAP
      enzyme activity in the serum or plasma of patient groups known to have increased
      bone metabolism. However, the poor stability of the enzyme and potential
      contribution from nonosteoclastic sources make it problematic to measure in
      patient samples. Immunoassays developed to measure TRAP in serum and plasma have
      yielded widely varying TRAP levels in both normal and disease states. It is not
      clear if this variability is caused by differences in assay calibration, antibody
      specificity, and/or TRAP instability. In this paper, we report that purified TRAP
      spiked into serum forms high molecular weight complexes. Complex formation
      results in greatly decreased TRAP enzyme activity and immunoreactivity. The
      complexing protein in serum has been identified as alpha2-macroglobulin
      (alpha2M). Similar complexes are observed in stored patient samples. In vitro
      studies with purified components show that TRAP binds to alpha2M primarily
      through noncovalent ionic interactions. Our results demonstrate that one
      mechanism of TRAP instability in serum is complex formation with alpha2M and
      suggest further that current TRAP enzyme and immunoassays may not accurately
      measure the circulating level of TRAP.

PMID- 9933488
TI  - Defining educational priorities in managed care: a symposium overview.

PMID- 9933490
TI  - Principles of generalist-specialist relationships.

PMID- 9933489
TI  - Financial incentives: current realities and challenges for physicians.

PMID- 9933491
TI  - Challenges in medical education: training physicians to work collaboratively.

PMID- 9933492
TI  - The doctor-patient relationship: challenges, opportunities, and strategies.

PMID- 9933494
TI  - The patient-provider relationship: opportunities as well as problems.

PMID- 9933495
TI  - Improving physicians' relationships with patients.

PMID- 9933493
TI  - Time and the patient-physician relationship.

PMID- 9933496
TI  - Rationale, principles, and educational approaches of organizational
      transformation.

PMID- 9933497
TI  - The role of bioethics and business ethics.

PMID- 9933498
TI  - Concluding thoughts--looking forward.

PMID- 9933499
TI  - Functions of SR and Tra2 proteins in pre-mRNA splicing regulation.

PMID- 9933500
TI  - Alternative splicing and programmed cell death.
AB  - Programmed cell death (PCD) is critical for development and homeostasis of
      multicellular organisms. Genetic and biochemical studies have revealed that PCD
      is under complex and delicate regulation. An important level of such regulation
      may be pre-mRNA splicing as suggested by the observation that a number of PCD
      regulatory genes are expressed as functionally distinct or even antagonistic
      isoforms as a result of alternative splicing. Studies on alternative splicing of
      these genes are reviewed here. Expression and function of a large number of genes
      involved in PCD are regulated by alternative splicing, including death receptors
      and intracellular components of the death machinery. Alternative splicing affects
      not only intracellular distribution but also functional activity of these death
      regulators, providing a fine-tuning mechanism in modulating a presumably tightly
      controlled process of cell death.

PMID- 9933501
TI  - Effects of cord blood transfer on the hematopoietic recovery following sublethal
      irradiation in MRL lpr/lpr mice.
AB  - The potential of cord blood (CB) to serve as a rich source of stem cells and stem
      cell factors is receiving increasing attention. In addition, perhaps because of
      the early ontogeny of these cells or the lack of surface antigens, cord blood
      stem cells do not appear to require close identity with the recipient. In the
      present pilot study, we investigated the presence of a hematopoiesis enhancing
      effect (HEE) by assaying the ability of human cord blood cells to augment
      hematopoiesis across a species barrier. For these experiments, autoimmune-prone
      MRL-Ipr/Ipr mice were exposed to sublethal levels of irradiation and cord blood
      administration to study the role of factors present in human cord blood in
      augmenting the rate of lymphopoiesis. This strain was chosen because of the
      increased presence of peripheral T and B subpopulations, namely the B-1 and
      CD4/CD8 double negative T-cell subpopulations, which do not arise directly from
      bone marrow precursors, but rather accumulate with age. MRL-Ipr/Ipr mice were
      sublethally irradiated and reconstituted with syngeneic bone marrow (BM) cells or
      with human cord blood cells or peripheral blood mononuclear cells (PBMC), or were
      left unreconstituted. At 2 weeks post-treatment, lymphoid populations in the
      spleen and lymph nodes were studied as a measure of hematopoiesis. Factors
      present in cord blood were able to augment hematopoiesis over that which occurred
      endogenously. At 2 weeks postirradiation, recipients of BM cells displayed the
      fastest rate of peripheral lymphoid recovery, nonreconstituted mice showed the
      slowest lymphoid recovery, and recipients of cord blood recovered their lymphoid
      populations at an intermediate rate. Similarly, myelopoiesis was increased in
      irradiated SJL/J recipients of human cord blood. Thus, human cord blood cells
      appear to produce/induce factors that may act as an adjunct to increase stem-cell
      activity.

PMID- 9933502
TI  - Prostaglandin E2 mediates activation of hypothalamic histamine by interleukin
      1beta in rats.
AB  - The present study was designed to investigate the effects of peripheral
      interleukin-1beta (IL-1beta) on hypothalamic histamine (HA) systems.
      Intraperitoneal injection of IL-1beta increased the turnover rate of hypothalamic
      HA, which was assessed by accumulation of tele-methylhistamine after pargyline
      treatment. IL-1beta increased the activities of both histidine decarboxylase
      (HDC), an HA synthesizing enzyme, and HA-N-methyltransferase (HMT), an HA
      catabolizing enzyme. Pretreatment with indomethacin completely blocked the
      effects induced by IL-1beta on hypothalamic HA. Infusion of prostaglandin E2
      (PGE2) into the third cerebroventricle increased the hypothalamic HA turnover
      rate, and simultaneously activated both HDC and HMT dose-dependently, but
      intravenous infusion of PGE2 had no effect on the dynamics of hypothalamic HA
      turnover. These results indicate that hypothalamic PGE2 activated by peripheral
      administration of IL-1beta, but not by peripheral PGE2, may enhance synthesis and
      release of hypothalamic HA by activation of HDC, and may facilitate degradation
      of extracellular histamine by activation of HMT.

PMID- 9933503
TI  - Developmental profile of prolactin cells in the anterior pituitary of postnatal
      rats during the lactational stage.
AB  - Changes in prolactin (PRL)-, growth hormone (GH)- and PRL/GH-containing cells in
      the anterior pituitary of pre- and postnatal male and female rats were determined
      using immunocytochemistry with double fluorescent antibodies. The pituitary
      glands from a fetus on Day 20 of gestation and pups on Days 0, 1, 4, 7, 12, and
      20 of the postnatal period with sex distinction were monodispersed and subjected
      to immunocytochemistry. Following immunostaining, the three types of cells
      described above were counted (i.e., only PRL-, only GH-, and both PRL and GH
      positive cells in a visual field of microscope). Anterior pituitaries and blood
      were obtained from pups on Days 0, 1, 4, 7, 12, and 20 after birth and pooled
      with sex distinction, and bioactive PRL levels in the anterior pituitary and
      serum were measured using an Nb2 rat lymphoma cell bioassay. Double fluorescent
      labeled immunocytochemistry was able to distinguish reliably between PRL-, GH-,
      and PRL/GH-containing cells. The PRL cells increased rapidly after parturition to
      4 days of age and after 12 days of age in both genders. The latter increase was
      involved in the remarkable increase of PRL/GH-containing cells, which were first
      found at term and remained at low levels until 12 days of age. The weight and PRL
      level of the anterior pituitary increased in both sexes throughout the
      lactational stage, but the levels in female rats at 20 days of age were
      significantly greater than those of male rats. Serum PRL concentration remained
      at low levels except on Day 0. The present results demonstrate that the
      development of PRL-containing cells in postnatal rats during the lactational
      period is activated with two distinct stages, at term to Day 4 and after Day 12,
      and the development in the latter stage is involved with sexual dimorphism.

PMID- 9933504
TI  - Lactic acid does not directly activate hypothalamic-pituitary corticotroph
      function.
AB  - The role that metabolic products play in regulating the hypothalamic-pituitary
      adrenal (HPA) axis during strenuous exercise is speculative. This investigation
      examined the extent to which lactic acid, a major metabolite of anaerobic
      exercise, directly affects hypothalamic-pituitary function. Specifically, beta
      endorphin secretion was measured from AtT-20 (D-16) mouse corticotroph tumor
      cells treated either acutely (15 min - 180 min) or chronically (1 day - 3 day)
      with physiologic levels of lactate (0. 5 x 10-3 M to 5 x 10-2 M) or lactate in
      combination with the corticotroph releasing factors: corticotroph releasing
      hormone (CRH), arginine vasopressin (AVP), norepinephrine and/or epinephrine.
      Findings with AtT-20 cell cultures were shown to be representative of responses
      in primary cultures of rat anterior pituitary. Lactic acid did not alter the
      spontaneous release of beta-endorphin by AtT-20 cells under either acute or
      chronic conditions. While CRH, norepinephrine, and epinephrine evoked significant
      increases in beta-endorphin release, lactate, in combination with these
      secretagogues did not alter their effects. Similarly, lactic acid failed to alter
      basal or stimulated release of beta-endorphin by primary cultures of rat anterior
      pituitary. The addition of lactate (3 x 103 M) to rat hypothalamic explants did,
      however, produce a modest but significant reduction in spontaneous CRH release,
      suggesting that lactate may facilitate the return to basal secretion following
      exercise. The present findings show that physiologic concentrations of lactate
      have no effect, either alone or in combination with other pituitary
      secretagogues, on corticotroph secretion. Whereas a physiologic action for
      lactate within the hypothalamus is possible, the present findings indicate that
      lactate is an inhibitor of CRH release. Thus, lactate does not appear to play a
      direct role in the profound activation of the HPA axis that occurs in response to
      strenuous exercise.

PMID- 9933505
TI  - Prenatal effects of caffeine and restraint stress in mice.
AB  - The maternal and developmental toxicity of combined exposure to restraint stress
      and caffeine was assessed in mice. On Day 9 of gestation, six groups of pregnant
      mice were treated (p.o.) with a single dose of 30, 60, or 120 mg/kg of caffeine.
      Immediately after caffeine administration, three of these groups were subjected
      to restraint for 14 hr. Control groups included unrestrained and restrained
      pregnant mice not exposed to caffeine. An additional group of animals
      (unrestrained and not exposed to caffeine) was deprived of food for 14 hr. A two
      way (caffeine dose x restraint) analysis of variance revealed an overall effect
      (reduction) of restraint and caffeine exposure on maternal body weight gain and
      food consumption on gestation Days 9-11. Significant reductions were also
      observed in body weight at termination and corrected body weight change of dams
      concurrently exposed to 120 mg/kg of caffeine and restraint. By contrast, no
      significant effects of caffeine, restraint, or caffeine plus restraint on
      embryo/fetal development were noted. The doses of caffeine administered here are
      much higher than those usually consumed by the general population. Under the
      current experimental conditions, caffeine alone or combined with restraint stress
      was not embryotoxic or teratogenic in mice.

PMID- 9933506
TI  - Ethanol's effect on rat pituitary adrenal axis is prevented by purine metabolic
      pathway inhibitors.
AB  - This study investigated the in vitro dose effects of ethanol (EtOH), adenosine
      (ADO), and urate (URA) on the basal and CRF stimulated ACTH production of
      pituitary tissue culture (PTC). Furthermore, the effects of low (LE = 0.5 g/kg
      bodyweight) and high (HE = 2.5 g/kg bodyweight) concentrations of EtOH were
      tested in rats on plasma ACTH and corticosterone concentration (PCC), with or
      without the following ADO metabolic pathway inhibitors: 6-mercaptopurine (6MP)
      (salvage pathway) and purpurogallin (PPG) (xanthine dehydrogenase). EtOH at 0-50
      mM does not increase the in vitro basal or CRF (10-7 M) stimulated ACTH secretion
      in PTC; in fact doses up to 20 mM tended to be inhibitory. ADO significantly
      increased only basal ACTH secretion whereas URA increased both basal and CRF
      stimulated ACTH secretion. Pretreatment with PPG or 6MP + PPG significantly
      increased both in vivo ACTH and PCC over control values in rats. HE versus LE
      significantly increased ACTH and PCC in the control (H2O) and 6MP pretreated
      groups whereas in the PPG pretreated animals, only ACTH was increased
      significantly by HE. However, combined pretreatment with 6MP + PPG prevented the
      effect of HE on ACTH and PCC. The current experiment suggests that purine
      metabolism is involved in ethanol's effect on the hypothalamic-pituitary-adrenal
      axis.

PMID- 9933507
TI  - The lateral view: a useful adjunct in the diagnosis of malrotation.

PMID- 9933508
TI  - Large-scale processing of recombinant retroviruses for gene therapy.
AB  - Gene therapy is a new therapeutic modality with the potential of treating
      inherited and acquired diseases. Several viral and physicochemical vehicles have
      been used for the transfer of genes to mammalian cells, but recombinant
      retroviruses are used in the majority of gene therapy clinical trials today. In
      this communication, we review the major concerns associated with the large-scale
      production and processing of retroviral particles. While some of the current
      processes for manufacturing recombinant proteins will be applicable to
      recombinant retroviruses, the instability, sensitivity to inhibitors, complexity,
      and size of retroviral particles require that new technologies be designed and
      evaluated. Here, we examine those issues critical to the design of strategies for
      production, concentration, and purification as well as formulation and storage of
      recombinant retroviruses. Processes for large-scale manufacturing of recombinant
      retroviruses that can produce high gene transfer efficiencies will have
      significant impact on the clinical implementation of gene therapy.

PMID- 9933509
TI  - Process engineering strategy for recombinant protein recovery from canola by
      cation exchange chromatography 
AB  - The suitability of canola as a recombinant protein production host was evaluated
      in terms of the potential for simple chromatographic recovery by ion exchange. To
      investigate the influence of the charge of a recombinant protein on recovery from
      canola, a series of mutants of T4 lysozyme of varying charge were used to model
      the situation of transgenic expression by being spiked into nontransgenic canola
      protein extracts. This mixture was then fractionated by cation exchange
      chromatography. Two different means of charge modification were compared, namely,
      point mutations and fusions. Point mutations proved the better means for adding
      positive charges. A linear relationship between the protein charge and the eluent
      conductivity, which could be used to guide the genetic engineering for protein
      recovery from canola, was found. It showed that an increase of +1 charge on T4
      lysozyme increased the required conductivity (molarity) of the eluent by 0.068
      mS/cm (27.8 mM NaCl). For this specific case, T4 lysozyme with a nominal charge
      of +7 moves the point of elution into a valley between two major native canola
      protein peaks, where substantial one-step enrichment can be obtained. Equivalent
      charge changes provided by polyarginine fusions gave very wide elution patterns
      that were ascribed to either proteolytic degradation within the polyarginine
      fusion or interaction of the polyarginine with polyanions present in canola.
      While the above results came after a dialysis step to adjust the canola extract,
      elimination of the dialysis step did not significantly influence the purification
      behavior of the cation-exchange column. However, a more severe resin regeneration
      scheme was needed to maintain the column's performance.

PMID- 9933510
TI  - Biomimetic peptide surfaces that regulate adhesion, spreading, cytoskeletal
      organization, and mineralization of the matrix deposited by osteoblast-like
      cells.
AB  - In an effort to regulate mammalian cell behavior in contact with solid material
      surfaces, we have functionalized surfaces with different ratios of both the
      putative cell binding (-Arg-Gly-Asp-) domain and a consensus heparan-binding
      domain. The peptide sequences -Arg-Gly-Asp- (-RGD-) and -Phe-His-Arg-Arg-Ile-Lys
      Ala- (-FHRRIKA-) or mixtures of the two in the ratios of 75:25 (mimetic peptide
      surface I), 25:75 (mimetic peptide surface II), and 50:50 (mimetic peptide
      surface III) were immobilized on model surfaces using a heterobifunctional cross
      linker to link the peptide(s) to amine-functionalized quartz surfaces. Contact
      angle measurements, spectroscopic ellipsometry, and X-ray photoelectron
      spectroscopy were used to confirm the chemistry, thickness of the overlayers, and
      surface density of immobilized peptides ( approximately 4-6 pmol/cm2). The degree
      of rat calvaria osteoblast-like cell spreading, focal contact formation,
      cytoskeletal organization, proliferation, and mineralization of the extracellular
      matrix (ECM) on model biomaterial surfaces was examined. Mimetic peptide surface
      II (MPS II) and MPS III supported the highest degree of cell spreading (p <
      0.05), following 4 h of incubation, compared to MPS I, homogeneous -RGD-, and
      homogeneous -FHRRIKA- grafted surfaces. Furthermore, MPS I, MPS II, MPS III, and
      homogeneous -RGD- surfaces promoted the formation of focal contacts and stress
      fibers by attached bone cells. The strength of bone cell detachment following 30
      min of incubation was significantly higher (p < 0.05) on MPS II surfaces compared
      to homogeneous -RGD- and -FHRRIKA-. However, the degree of cell proliferation on
      the peptide surfaces were not significantly different from each other (p > 0.1).
      Following 24 d in culture, the areas of mineralized ECM formed on MPS II and MPS
      III surfaces were significantly (p < 0.05) larger than those of other surfaces.
      These results demonstrate that utilizing peptide sequences incorporating both
      cell- and heparin-adhesive motifs can enhance the degree of cell surface
      interactions and influence the long-term formation of mineralized ECM in vitro.

PMID- 9933512
TI  - GlaA promoter controlled production of a mutant green fluorescent protein (S65T)
      by recombinant aspergillus niger during growth on defined medium in batch and fed
      batch cultures 
AB  - The first successful expression of the Aequorea victoria green fluorescent
      protein (GFP) gene in Aspergillus niger is described. When the wild-type GFP gene
      was expressed in A. niger, neither the fluorescence nor the full translation
      product of the wtGFP gene was detectable. However, the expression of a mutant
      form of the green fluorescent protein (S65TGFP) gene resulted in the formation of
      a functional fluorescent polypeptide. The synthesis of S65TGFP was used to study
      glaA promoter controlled heterologous gene expression by recombinant A. niger in
      batch and fed-batch cultures using a defined growth medium. Cells were grown on
      xylose as noninducing carbon source, and the production of S65TGFP was
      accomplished by the addition of maltose. The recombinant protein accumulated up
      to 10 or 25 mg of S65TGFP g-1 cell dry weight using either a maltose pulse for
      induction or continuous addition of the inducing carbon source, respectively.
      Irrespective of the induction protocol, the recombinant protein started to
      accumulate 2 h after addition of the inducing carbon source and reached its
      maximum specific concentration 10 h after induction. Bright green fluorescing
      fungal pellets were first detectable by fluorescence microscopy 4-5 h after the
      onset of maltose addition.

PMID- 9933511
TI  - Short-term cell/substrate contact dynamics of subconfluent endothelial cells
      following exposure to laminar flow.
AB  - The manner in which fluid stresses are transmitted from the apical to the basal
      surface of the endothelium will influence the dynamics of cell/substrate
      contacts. Such dynamics could be important in the design of synthetic vascular
      grafts to promote endothelial cell adhesion. To examine whether the initial
      response of cell/substrate contact sites to flow depends on the magnitude of the
      applied shear stress, subconfluent monolayers of endothelial cells were exposed
      to flow at 10, 20, and 30 dyn cm-2 wall shear stresses for 20 min. Cell/substrate
      contact sites were visualized with total internal reflection fluorescence
      microscopy. Flow induced a rapid fluctuation in the membrane topography, which
      was reflected in dynamic changes in cell/substrate contacts. Exposure to flow
      caused marked changes in contact area. Contact movement occurred normal and
      parallel to the direction of flow. Contact sites demonstrated significant
      variability in contact area at 30 dyn cm-2 during the experiment but no
      significant movement of the contact sites in flow direction after 20 min of flow.
      Mean square displacements of the contact center of mass were described in terms
      of a directed diffusion model. Prior to onset of flow, contact movement was
      random. Flow induced a significant convective component to contact movement for
      300-600 s, followed by reestablishment of diffusive growth and movement of
      contacts. These results suggest that fluid stresses are rapidly transmitted from
      the apical to the basal surface of the cell via the cytoskeleton.

PMID- 9933513
TI  - Quantitative model for Gal4p-mediated expression of the galactose/melibiose
      regulon in Saccharomyces cerevisiae.
AB  - A mathematical model based on equilibrium binding between Gal4p and its specific
      DNA binding site has been developed. A model for GAL gene expression solely due
      to cooperativity, as a function of Gal4p concentration, has been developed for a
      gal80 mutant. The above model was extended to include other known regulatory
      molecules, namely Gal80p and Gal3p. Parameters determined from the above
      simulation were then used to represent a physiological status of gene expression
      in response to glucose (in terms of Gal4p concentration) and galactose in a wild
      type strain. We demonstrate that in a wild-type strain glucose repression is more
      stringent due to cooperativity and autogenous regulation, while the induction
      response to galactose is only through autogenous regulation. The biological
      significance of autogenous regulation in Saccharomyces cerevisiae is discussed
      vis-a-vis the lactose operon of Escherichia coli.

PMID- 9933514
TI  - Library of synthetic 5' secondary structures to manipulate mRNA stability in
      Escherichia coli.
AB  - A DNA cassette system has been developed to allow for the convenient introduction
      of synthetic DNA oligonucleotides between the transcription and translation start
      sites of a gene in order to examine the effect of 5' hairpin structure and
      strength on mRNA stabilization. Rationally designed synthetic DNA cassettes were
      introduced into the 5' untranslated region of a modified lacZ gene to form
      hairpins at the 5' end of the mRNA. These DNA inserts influenced mRNA half-lives
      over an order-of-magnitude range, with some groups of predicted structures having
      half-lives that showed a strong correlation with hairpin strength while half
      lives for another group of predicted structures exhibited little or no dependence
      on this property. These results indicate the importance of 5' hairpin structure
      and strength in determining stabilization of Escherichia coli mRNA. This
      synthetic library, as well others generated using the DNA cassette system
      described here, should prove useful in understanding the mechanisms of mRNA
      stabilization and in designing structures for recombinant gene expression
      control.

PMID- 9933515
TI  - NMR-Observed phosphate trafficking and polyphosphate dynamics in wild-type and
      vph1-1 mutant Saccharomyces cerevisae in response to stresses.
AB  - The phosphagenic, osmotic, and metabolic roles of polyphosphate in chemostat
      cultivated yeast were investigated with a new NMR cultivator. Wild-type yeast and
      a vacuolar vph1-1 mutant, which lacks polyphosphate, were subjected to different
      stimuli. Starved wild-type yeast exclusively directed phosphate to vacuoles
      despite other competing sinks. After DNP or iodoacetate exposure, which
      significantly affected cytosolic pH or ATP metabolism, polyphosphate hydrolysis
      did not occur, which casts doubt on the phosphagen function of vacuolar
      polyphosphate. It took about 1 h for Mn2+ to traffic to vacuoles, and some
      evidence was obtained for polyphosphate responding to osmotic challenges. Fast
      NMR scans show that rapid polyphosphate hydrolysis to small polymers follows
      alkalinization. The small polymers then degrade to orthophosphate, which
      coincides with sugar phosphates increasing and subsequent reacidification. In
      contrast, when vph1-1 mutants were subjected to alkalinization, the absence of a
      vacuolar source of phosphate slowed reacidification. Based on known yeast
      physiology and observed sugar phosphate dynamics, polyphosphate degradation may
      enable rapid glycogen mobilization to glycolysis for considerable acid and ATP
      production. Overall, maintaining both polyphosphate and carbohydrate reserves may
      endow yeast with the ability to rapidly manage the extracellular environment.

PMID- 9933516
TI  - Simultaneous biodegradation of benzene, toluene, and p-xylene in a two-phase
      partitioning bioreactor: concept demonstration and practical application.
AB  - In this work, a mixture of benzene, toluene, and p-xylene was simultaneously
      biodegraded by Pseudomonas sp. ATCC 55595 in a two-phase partitioning bioreactor.
      This bioreactor consisted of a 1-L cell-containing aqueous medium phase and a 500
      mL immiscible organic phase. The organic solvent systematically selected for use
      in the bioreactor was Adol 85 NF, an industrial-grade, biocompatible solvent. In
      the first of three experiments, the organic phase was loaded with 2.0 g of
      benzene, 10.15 g of toluene, and 2.1 g of p-xylene, which partitioned into the
      aqueous phase at concentrations of 25, 50, and 8 mg/L, respectively. The system
      ultimately biodegraded all of the substrates within 144 h. During the rapid
      growth phase of this fermentation, the cells were oxygen-limited. This
      fermentation was therefore repeated using an enriched air supply to remove the
      oxygen limitation. The use of enriched air ultimately reduced the length of the
      fermentation to 108 h, thereby improving the overall volumetric consumption
      rates. Finally, 500 mL of Adol were used to recover 2.0 g of benzene, 10.15 g of
      toluene, and 2.1 g of p-xylene from silica sand that was contaminated as part of
      a simulated soil "spill". The solvent washing procedure was able to recover
      greater than 99% of each compound from the contaminated soil. The Adol was then
      transferred to the two-phase bioreactor to permit biological treatment of the BTX
      contaminants. This process was repeated when the initial BTX load had been
      consumed almost to exhaustion, and the solvent was able to recover the
      contaminants at greater than 99% efficiency once again. The system was ultimately
      able to degrade 4.0 g of benzene, 20.2 g of toluene, and 4.2 g of p-xylene within
      144 h. These results represent an unprecedented level of BTX degradation and
      illustrate a potential practical application for this novel biotechnology.

PMID- 9933518
TI  - Wastepaper hydrolysate as soluble inducing substrate for cellulase production in
      continuous culture of trichoderma reesei 
AB  - The enzymatic hydrolysate of wastepaper was evaluated for its cellulase-inducing
      capability and production characteristics in continuous culture of Trichoderma
      reesei RUT C30. Under the study conditions, i.e., pH 5.0, temperature 25
      degreesC, and typical medium C:N ratio, the apparent cell yield constant was
      found to be 0. 76 (g of dry cell weight/g of reducing sugar), and the maximum
      specific cell growth rate was 0.26 h-1. The study on the effects of medium C:N
      ratio confirmed an important role of N sources in the cellulase synthesis. The
      cellulase production decreased significantly when the feed concentrations of N
      sources were reduced. An experiment at pH 7.5 with 4-fold N source concentrations
      also led to poorer cellulase production. When compared with cellulose, the
      wastepaper hydrolysate was found to have similar cellulase-inducing strength and
      to induce an apparently complete set of cellulase components. The hydrolysate was
      also concluded to be a better soluble inducer than sophorose. While comparable at
      a low dilution rate (0.012 h-1), the specific cellulase productivities of the
      hydrolysate-supported and the sophorose-induced systems exhibited opposite trends
      with increasing dilution rates. The specific productivity in sophorose-induced
      systems decreased with an increase in the dilution rate. On the other hand, with
      increasing dilution rate the specific productivity in the hydrolysate-supported
      systems increased from 2.2 FPU/g.h at D = 0.012 h-1 to 12.2 FPU/g.h at D = 0.122
      h-1 before beginning to decline. The initial increasing trend was attributed to
      the higher concentrations of inducing oligomer intermediates at larger dilution
      rates.

PMID- 9933517
TI  - Modeling of overflow metabolism in batch and fed-batch cultures of Escherichia
      coli.
AB  - A dynamic model of glucose overflow metabolism in batch and fed-batch
      cultivations of Escherichia coli W3110 under fully aerobic conditions is
      presented. Simulation based on the model describes cell growth, respiration, and
      acetate formation as well as acetate reconsumption during batch cultures, the
      transition of batch to fed-batch culture, and fed-batch cultures. E. coli
      excreted acetate only when specific glucose uptake exceeded a critical rate
      corresponding to a maximum respiration rate. In batch cultures where the glucose
      uptake was unlimited, the overflow acetate made up to 9. 0 +/- 1.0% carbon/carbon
      of the glucose consumed. The applicability of the model to dynamic situations was
      tested by challenging the model with glucose and acetate pulses added during the
      fed-batch part of the cultures. In the presence of a glucose feed, E. coli
      utilized acetate 3 times faster than in the absence of glucose. The cells showed
      no significant difference in maximum specific uptake rate of endogenous acetate
      produced by glucose overflow and exogenous acetate added to the culture, the
      value being 0.12-0.18 g g-1 h-1 during the entire fed-batch culture period.
      Acetate inhibited the specific growth rate according to a noncompetitive model,
      with the inhibition constant (ki) being 9 g of acetate/L. This was due to the
      reduced rate of glucose uptake rather than the reduced yield of biomass.

PMID- 9933519
TI  - An unusual reversible sol-Gel transition phenomenon in organogels and its
      application for enzyme immobilization in gelatin membranes 
AB  - An unusual phenomenon is observed for gelatin solutions (1.7-6.8%) in the
      microemulsion system of 0.3 M bis(2-ethylhexyl)sulfosuccinate sodium salt in
      isooctane and 14.5% distilled water. Highly viscous gels obtained at temperatures
      above 30 degreesC become free-flowing liquids at low temperatures (5-10
      degreesC). This reversible temperature-dependent sol-gel transition phenomenon is
      used to immobilize several enzymes, such as lipase from Candida rugosa, alcohol
      dehydrogenase from baker's yeast, mandelonitrile lyase from Sorghum bicolor, and
      horseradish peroxidase in the gelatin matrix by solubilizing the enzyme in a
      microemulsion-based gelatin solution at low temperature (<5 degreesC) and then
      cross-linking with glutaraldehyde. The enzymes retain 70-80% of their activity
      after immobilization and can be used in biotransformations in organic solvents
      without any changes in enantioselectivity. This work provides a unique low
      temperature technique for enzyme immobilization in a biocompatible gelatin matrix
      with a great flexibility of size and shape.

PMID- 9933520
TI  - Immobilized yeast bioreactor systems for continuous beer fermentation 
AB  - Two different types of immobilized yeast bioreactors were examined for continuous
      fermentation of high-gravity worts. One of these is a fluidized bed reactor (FBR)
      that employs porous glass beads for yeast immobilization. The second system is a
      loop reactor containing a porous silicon carbide cartridge (SCCR) for
      immobilizing the yeast cells. Although there was some residual fermentable sugar
      in the SCCR system product, nearly complete attenuation of the wort sugars was
      achieved in either of the systems when operated as a two-stage process.
      Fermentation could be completed in these systems in only half the time required
      for a conventional batch process. Both the systems showed similar kinetics of
      extract consumption, and therefore similar volumetric productivity. As compared
      to the batch fermentation, total fusel alcohols were lower; total esters, while
      variable, were generally higher. The yeast biomass production was similar to that
      in a conventional fermentation process. As would be expected in an accelerated
      fermentation system, the levels of vicinal diketones (VDKs) were higher. To
      remove the VDKs, the young beer was heat-treated to convert the VDK precursors
      and processed through a packed bed immobilized yeast bioreactor for VDK
      assimilation. The finished product from the FBR system was found to be quite
      acceptable from a flavor perspective, albeit different from the product from a
      conventional batch process. Significantly shortened fermentation times
      demonstrate the feasibility of this technology for beer production.

PMID- 9933521
TI  - Development of a low capital investment reactor system: application for plant
      cell suspension culture 
AB  - Growth of plant cell cultures is demonstrated in an uncontrolled, simple, and
      inexpensive plastic-lined vessel. Sustained specific growth rates of 0.22 day-1
      for Hyoscyamus muticus cell suspension cultures are achieved in a low-cost gas
      sparged bioreactor configuration (6.5 L working volume, wv) which is comparable
      to an "optimized" 5 L wv mechanically agitated fermentor. In an effort to reduce
      bioreactor costs, the need for an autoclavable vessel was eliminated.
      Sterilization is achieved by separate autoclaving of the plastic liner and by gas
      phase sterilization using ethylene oxide. The initial run sterilized with
      ethylene oxide displayed a long lag, apparently due to residual sterilant gas.
      Because ethylene oxide could eliminate costs associated with autoclave rated
      vessels, a quantitative basis for aeration time was developed by experimental
      measurements and modeling of diffusion in the polymer liner. Operational
      techniques to eliminate toxicity are implemented to grow 0.2 kg dry weight of
      plant cells in 13 days in a 40 L (28.5 L wv) air-lift bioreactor without
      autoclave sterilization. The biomass yields for all reactors were statistically
      indistinguishable from shake flask culture.

PMID- 9933523
TI  - Fiber-optic enzyme biosensor for direct determination of organophosphate nerve
      agents.
AB  - A fiber-optic enzyme biosensor for the direct measurement of organophosphate
      nerve agents was developed. The basic element of this biosensor is
      organophosphorus hydrolase immobilized on a nylon membrane and attached to the
      common end of a bifurcated optical fiber bundle. The enzyme catalyzes the
      hydrolysis of organophosphate compounds to form stoichiometric amounts of
      chromophoric products that absorb light at specific wavelengths. The back
      scattered radiation of the specific incident radiation was measured using a
      photomultiplier detector and correlated to the organophosphate concentration. The
      effects of buffer pH, temperature, and the units of enzyme immobilized on the
      steady-state and kinetic response of the biosensor were investigated to optimize
      the operating conditions for the fiber-optic enzyme biosensor. These conditions
      were then used to measure parathion, paraoxon, and coumaphos selectively without
      interference from carbamates and triazines. Concentrations as low as 2 microM can
      be measured in less than 2 min using the kinetic response. When stored in buffer
      at 4 degreesC the biosensor shows long-term stability.

PMID- 9933524
TI  - In situ detoxification of the fermentation medium during gamma-decalactone
      production with the yeast sporidiobolus salmonicolor 
AB  - gamma-Decalactone (gamma-C10) is known to be highly toxic for the microorganims
      used for its production. In this work, three techniques were studied in order to
      overcome this toxicity during a bioconversion process using ricinoleic acid as
      precursor of the lactone: in situ trapping in oily phases, in porous hydrophobic
      sorbents and in beta-cyclodextrins. Oily phases added to the media (olive,
      Miglyol, tributyrin, and paraffin) had a protective effect on Sp. salmonicolor,
      and they improved the lactone production. beta-cyclodextrins, which have a
      hydrophobic cavity that can trap molecules such as gamma-C10, have been used to
      protect the yeasts. The results showed insufficient preservation of cell
      viability. Some sorbents (activated carbon and polystyrene-based sorbents) were
      successfully tested during bioconversion. In all cases viability exceeded the
      reference one. Nevertheless the aroma production was 30% lower than the
      reference. All of these solutions led to some enhancement of the cell viability
      during bioconversion of methyl ricinoleate to gamma-C10. For improvement of the
      lactone production, the oil trapping method seemed to be the best with the
      experimental conditions tested.

PMID- 9933522
TI  - Growth rate related concentration changes of the starvation response regulators
      sigmaS and ppGpp in glucose-limited fed-batch and continuous cultures of
      Escherichia coli.
AB  - The entry of Escherichia coli into glucose starvation is connected to the
      induction of both the stringent response and the general stress response. The
      concentration of the corresponding response regulators ppGpp and sigmaS (RpoS,
      KatF) was investigated during glucose-limited growth at different growth rates
      and with different cultivation strategies, including fed-batch fermentation,
      chemostat, and a continuous-cultivation technique with computer-controlled
      decrease of the feeding rate (A-stat). This study confirms the model of the in
      vivo effect of ppGpp on sigmaS by the direct measurement of ppGpp and sigmaS
      levels. The response of both regulators was clearly shown in situations where a
      nutrient shift occurs. A correlation in the concentration of both regulators was
      also shown under steady-state conditions. However, during transients with slow
      continuous changes of the nutrient availability, this concerted reaction of ppGpp
      and sigmaS is less apparent, indicating the specific importance of these
      regulators for the adaptation of the cells to fast changes of environmental
      parameters.

PMID- 9933525
TI  - Improvement of biomass yield and recombinant gene expression in Escherichia coli
      by using fructose as the primary carbon source.
AB  - The feasibility of substituting glucose with fructose as a carbon source in
      Escherichia coli fermentations was investigated. Glucose, the most commonly used
      sugar in bacterial cultivations, is well-known to pose a number of drawbacks; the
      most important of which is the Crabtree effect, which results in acidogenesis.
      Fructose, a glucose structural isomer, offers a reasonable alternative for
      glucose, since its uptake and utilization are more tightly regulated. Comparative
      fermentation studies indicate that lower acetate excretion and higher biomass
      yields were attained in fructose-supplemented growth media compared with those of
      glucose media. More specifically, cells grown in defined media supplemented with
      fructose do not excrete detectable amounts of acetate, while about 40 mM of
      acetate was detected extracellularly in similar glucose cultures. A reduction in
      the initial growth rate of about 20% was observed with fructose, but final cell
      densities were about 70% higher compared with glucose supplements. Growth in
      complex LB media supplemented with fructose again resulted in higher biomass
      yields (up to 40%) and lower acetate excretion (30-40%) than the comparable
      glucose media. In bioreactor studies using LB media, acetate levels were reduced
      from 90 to less than 6 mM, while achieving a 25% improvement in biomass yield.
      When using richer media, cell densities of more than 40 g L-1 dry cell weight
      were attained in batch cultivation using fructose compared with 30 g L-1 for
      glucose. These results have immense applicability in the area of recombinant
      protein processes. Recombinant E. coli, overexpressing beta-galactosidase under
      the control of the strong pH-inducible promoter, achieved a volumetric
      recombinant protein yield of 2.2 million U mL-1 (corresponding to approximately
      1.5 g L-1) in batch fructose cultures. This represents a 65% recombinant protein
      yield enhancement when compared to similar glucose cultivations.

PMID- 9933526
TI  - Glycosylation of CHO-derived recombinant tPA produced under elevated pCO2 

PMID- 9933527
TI  - Sex roles and sexual selection.
AB  - Sexual selection has been portrayed as acting predominantly on males who compete
      with each other over copulatory access to females; selection was considered to be
      driven by females choosing between males at the pre- or postcopulatory level.
      However, a broader view of sexual selection is now emerging. Examining male
      discrimination between females and female-female competition has been beneficial
      in identifying factors influencing the direction and strength of sexual
      selection. Furthermore, consideration of processes such as sexual coercion or
      genetic incompatibility, which indirectly influence an individual's set of
      copulation partners, gamete set or their offspring success, has helped to clarify
      the ways in which sexual selection may operate. Moreover, there is increasing
      evidence that not all copulations translate directly to paternity and that
      paternity does not necessarily translate into successful offspring.
      Postcopulatory and postfertilization mechanisms that influence not only paternity
      share but offspring recruitment now require further consideration. The benefits
      to each sex of copulating with particular partners or with more than one partner
      remains an area of debate. More carefully designed studies which eliminate
      alternative possibilities or quantify the relative importance of different
      selective pressures will also benefit from considering that not all copulations
      function solely to inseminate or receive sperm. It is also now clear that not all
      individuals of one sex follow the same strategy. Examining the variation between
      individuals in reproductive behaviour, fertilization success and offspring
      success will be important in establishing the selective pressures and mechanisms
      underlying the operation of sexual selection. (c) 1998 The Association for the
      Study of Animal Behaviour.

PMID- 9933529
TI  - Hunting by male lions: ecological influences and socioecological implications.
AB  - In the Kruger National Park, male lions, Panthera leo, acquire most of their food
      by hunting rather than scavenging. This study, the most intensive to date of male
      lion ecology, showed that in savanna woodlands, with high buffalo, Syncerus
      caffer, densities, male lions were frequent and successful hunters. The main prey
      species of all male group types, but particularly nonterritorial males, was
      buffalo. By contrast, females preyed more frequently on the most abundant medium
      sized ungulates, such as wildebeest, Connochaetes taurinus, and zebra, Equus
      burchelli. Thus intraspecific prey selection separation was based primarily on
      intersexual and, to a lesser extent, social differences. Furthermore, both
      nonterritorial males and pride females located their favoured prey, buffalo and
      medium-sized ungulates, respectively, more often than other prey. We investigated
      the influence of several ecological variables on the socioecology of male lions,
      particularly as we had determined that territorial males spent little time with
      their pride females and tended to hunt by themselves in their respective male
      coalitions. Further analysis showed that in a range of ecosystems in southern and
      eastern Africa the proportion of time territorial males spent with, and thus
      scavenged from, their pride females was strongly influenced by vegetation
      structure, and therefore probably by the assemblage of available ungulates. In
      open systems, territorial males were, therefore, likely to be encountered with
      pride females, whereas in more wooded areas they were likely to be encountered
      away from their pride females. We suggest that this is because vegetation
      structure influences food/prey availability and hunting success and influences
      territory maintenance and/or cub defence. (c) 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9933528
TI  - Brood parasitism in the sand martin, Riparia riparia: evidence for two parasitic
      strategies in a colonial passerine.
AB  - Sand martin parentage was studied at a large breeding colony in central Scotland.
      Multilocus DNA fingerprinting was used during the 3-year study to exclude some
      social parents as true parents, and thereby determine the frequency of monogamy,
      quasiparasitism (QP), intraspecific brood parasitism (ISBP) and extrapair
      fertilization (EPF) amongst 45 broods and 167 nestlings. Monogamous parentage
      characterized the majority of broods (60%), so most chicks were the offspring of
      their social parents (81%). QP (involving a male's extrapair mate laying in his
      nest) was found in 9% of broods and 2.4% of chicks and ISBP (or 'egg dumping') in
      4% of broods and 1.8% of chicks. A substantial proportion of offspring arose from
      EPFs, affecting 36% of broods and 14% of chicks. On present evidence, the
      relatively high frequency of QP found in sand martins is unusual. We propose that
      its observed frequency is unlikely to be due to chance events and may represent a
      female-driven strategy. (c)1998 The Association for the Study of Animal
      Behaviour.

PMID- 9933530
TI  - Observation learning in day-old chicks using a one-trial passive avoidance
      learning paradigm.
AB  - We tested the hypothesis that day-old chicks, Gallus gallus domesticus, can learn
      to avoid an aversive stimulus if they observe the responses of another chick. In
      experiment 1, one of a pair of chicks (the actor) was allowed to peck at a bead
      coated in the bitter-tasting substance methylanthranilate (MeA), while we
      prevented the other chick (the observer) from pecking the bitter-tasting bead by
      separating the chicks with a piece of wire mesh. Both chicks avoided pecking at a
      similar but dry bead 0.5, 3 and 24 h after the observer chick saw the actor chick
      peck at an MeA-coated bead. By contrast, when the actor chick had pecked at a
      water-coated bead, both chicks continued to peck at a dry bead at 0.5, 3 and 24 h
      after training. Experiment 2 investigated whether observer chicks showed
      avoidance if they were prevented (by the insertion of an opaque barrier) from
      observing their companion pecking at the MeA-coated bead during either training
      or testing. Observer chicks that could not see their companion during training
      but could observe the actor chicks at test showed no subsequent avoidance whereas
      chicks that observed the actor chick at training, but not during testing, showed
      high levels of avoidance. Although the sensory cues (visual, auditory or
      olfactory) or types of behaviour (i.e. levels of pecking or head shaking) that
      the observer chick used to maintain avoidance remain unclear, the results show
      that chicks can learn about an aversive object by observing the responses of a
      conspecific. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933531
TI  - Causes and consequences of natal dispersal in root voles, Microtus oeconomus.
AB  - To test the causes and consequences of variation in natal dispersal in root voles
      we released 53 matrilines (mothers with newly weaned litters) separately in field
      enclosures, during nine consecutive periods. The matrilines could disperse and
      distribute themselves among three pre-emptied habitat patches. Two dispersal
      measures were recorded: short-distance dispersal defined as individuals
      immigrating to a neighbouring patch, and long-distance dispersal defined as
      unsettled individuals captured along the fence of the enclosures. We analysed the
      role of social factors (i.e. maternal and litter characteristics), habitat
      quality (i.e. seasonal effect) and experimentally manipulated shape of the natal
      patch in dispersal. The consequences of dispersal were analysed with respect to
      the spatial distribution of kin, and to pregnancy in females and sexual
      maturation in males. Dispersal was unrelated to patch shape. In agreement with
      the inbreeding avoidance hypothesis, long-distance dispersal was male biased and
      philopatric males were most frequently reproductively inactive. Whilst young
      males avoided their mother, they seemed to disperse, settle and mature sexually
      independently of their sisters. In agreement with the resource competition
      hypothesis, young females avoided their mother and were most frequently
      reproductively inactive when residing in their mother's patch. We conclude that
      inbreeding avoidance was underlying the male dispersal pattern. For females, long
      distance dispersal was most in agreement with the inbreeding avoidance hypothesis
      while short-distance dispersal could be explained by the resource competition
      hypothesis. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933532
TI  - Relative competitive ability changes with competitor density: evidence from
      feeding blackbirds.
AB  - How individual competitive ability varies with competitor density in systems
      where interference competition occurs has been studied in few systems, despite
      its importance in determining the fundamental predictions of influential
      phenotype-limited ideal free distribution models. I measured individual variation
      in competitive ability in wild wintering blackbirds, Turdus merula. Variation in
      feeding rate of single birds, and the decline in their feeding rate in the
      presence of competitors, were measured in experimental patches. Individuals
      varied significantly both in their feeding rate when alone and in the decline in
      that feeding rate in the presence of competitors. Individuals that had high
      absolute feeding rates did not tend to have smaller declines in feeding rate in
      the presence of competitors. The relative ranking among birds in their feeding
      rate was strongly dependent on competitor density. This result has important
      implications for the expected distributions of competitors between patches. (c)
      1998 The Association for the Study of Animal Behaviour.

PMID- 9933533
TI  - Behavioural time-energy budgets of cooperatively breeding Neolamprologus pulcher
      (Pisces: Cichlidae).
AB  - We estimated the energy expenditures resulting from helping behaviour in the
      cooperatively breeding cichlid N. pulcher by measuring the metabolic rates
      directly associated with specific social and territory maintenance behaviours of
      individual pair males and females, and their helpers, in a respirometer. In pair
      males, pair females and helpers, routine metabolism was raised on average 4.4,
      3.8 and 3.6 times, respectively, during agonistic behaviour. Helpers spent 3.3
      and 6.1 times routine metabolism, respectively, on submissive behaviour (tail
      quivering) and digging. These estimates of energy expenditure were combined with
      laboratory time budgets, obtained previously, to calculate behavioural time
      energy budgets for pair members and helpers. Both groups spent on average 98.5%
      of total metabolism on routine and standard metabolism. With regard to the energy
      expended on specific behaviours, pair males invested almost exclusively in
      intrafamily agonistic behaviour, while pair females and helpers shared the
      investment in territory maintenance and direct brood care. The behavioural energy
      budget of helpers was strongly determined by their submissive behaviour. This
      serves to maintain the social status of the helpers within the family hierarchy
      and may therefore be regarded as 'paying for staying', which may also be true for
      direct brood care and other helper duties. We conclude that the substantial
      energy expenditures associated with helping behaviours are probably partly
      responsible for the reduced growth rates of helpers. This is the first study in
      which energy expenditures associated with specific helping behaviours have been
      measured in brood care helpers, and it provides the first estimate of total
      behavioural energy expenditure in a cooperatively breeding fish. (c) 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9933534
TI  - Artificial neural networks as models of stimulus control.
AB  - We evaluate the ability of artificial neural network models (multilayer
      perceptrons) to predict stimulus-response relationships. A variety of empirical
      results are considered, such as generalization, peak shift (supernormality) and
      stimulus intensity effects. The networks were trained on the same tasks as the
      animals in the experiments considered. The subsequent generalization tests on the
      networks showed that the model replicates correctly the empirical results. We
      conclude that these models are valuable tools in the study of animal behaviour.
      (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933535
TI  - Uniform discrimination of pattern orientation by honeybees.
AB  - To explore how honeybees, Apis cerana, discriminate the orientation of patterns,
      we trained workers to discriminate between a black stripe of a certain
      orientation on a white disc and a pure white disc. We tested trained bees for
      their ability to discriminate between the trained orientation and deviations from
      it. This was done either in a dual choice situation where the bees had to choose
      between the trained orientation and one deviation from it at a time, or in a
      multiple choice situation where bees had to choose simultaneously between the
      trained orientation and 11 successive deviations from it. In the dual choice
      situation, bees did not discriminate behaviourally between the trained
      orientation and deviations up to 25 degrees, whereas in a multiple choice
      situation, they discriminated between the trained orientation and a deviation of
      15 degrees or more. Thus, orientation can be analysed more precisely in multiple
      choice experiments. The response of the bees was independent of the orientation
      of the trained orientation; the 12 different trained orientations all yielded
      identical results. This finding, considered together with a model that we present
      for orientation discrimination, suggests that at least three orientation
      sensitive channels (a neuron or a set of neurons that respond maximally to a
      particular orientation) participate in the analysis of pattern orientation. (c)
      1998 The Association for the Study of Animal Behaviour.

PMID- 9933536
TI  - Assortative mating and female clutch investment in black grouse.
AB  - Variation in female behaviour has only recently received attention in studies of
      sexual selection. It has been suggested that females may invest differentially in
      their offspring in relation to the quality of their mate. This may lead to
      females that mate with high-quality and/or attractive males laying larger
      clutches. Females may also differ in their ability to choose between males. For
      example, females in good physical condition may make better choices. If physical
      condition and clutch size are positively correlated, this hypothesis could also
      produce a relationship between male attractiveness and female clutch size. We
      found, in lekking black grouse, Tetrao tetrix, that females mated to the highest
      ranked males laid the largest clutches. Furthermore we found, regardless of
      female age, a positive relationship between a measure of female condition and
      male rank but not between female condition and her clutch size. In addition,
      females in good condition visited a larger number of different male territories,
      and old females produced the largest clutches. Our results suggest two mechanisms
      to explain our findings. First, females in good physical condition tend to mate
      with the top males, suggesting an assortative mating pattern. Second, females
      mating with the highest ranked males lay larger clutches as a consequence of
      their choice. In general, our result calls for caution in evaluating studies that
      look at the consequences of mate choice. It may be that differences in female
      quality produce effects that may be wrongly interpreted as male quality effects.
      (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933537
TI  - Sexual selection as a side-effect of sexual conflict in the seaweed fly, Coelopa
      ursina (Diptera: Coelopidae).
AB  - The mating system of the seaweed fly involves a premating struggle. When mounted,
      females violently try to remove the male. In this study 48% of premating
      struggles resulted in successful rejection of the male, 46% in copulation and 6%
      were terminated by the male. Large males had a mating advantage. However,
      contrary to what would be predicted if this sexual selection occurred as a result
      of active female mate choice, we found a positive association between the
      duration of premating struggles and male size. A positive association was also
      found between the duration of premating struggles and male mating success,
      suggesting that large males may benefit through their superior ability to
      withstand female rejection. Large females rejected males more easily than small
      females, suggesting that the premating struggle has not evolved to allow mate
      assessment by females. We conclude that sexual selection is occurring as a side
      effect of the female rejection response, which has probably evolved in order to
      avoid costs associated with copulation. Nevertheless, a sexual size dimorphism
      has evolved with males being larger and much more variable in size than females.
      (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933538
TI  - Potential fitness benefits of group living in the red fox, Vulpes vulpes.
AB  - For species such as the red fox, spatio-temporal variation in resource
      availability may promote group living even when the benefits of group formation
      are not of significant magnitude to promote territorial expansion and delayed
      dispersal. In this paper we use data from an urban fox population to compare the
      relative benefits of dispersal and natal philopatry as routes to attaining
      dominant status and investigate the potential benefits of territory inheritance,
      alloparental care and reproduction to subdominant individuals. More offspring, of
      either sex, remained on their natal territory than dispersed. The annual rate of
      retention of dominant status and the annual mortality rate of subdominant animals
      was high, such that the majority of subdominant animals never became dominant.
      The mortality rate of dispersing individuals was also high. The relative success
      rate of dispersal and philopatry as routes to dominance were broadly similar,
      although several philopatric offspring became dominant only after their natal
      territory was divided: in the absence of such changes, dispersal was more likely
      to lead to dominant status. Thus, it is likely that some other benefit was
      accrued by philopatric individuals. The majority of subdominants provisioned
      cubs. This did not increase the number of cubs reared but reduced the level of
      provisioning by dominants: whether this promoted dominants' longevity is unknown.
      There were high levels of reproduction by subordinate females and the levels of
      alloparental care by subdominants of both sexes suggest that there are comparable
      levels of direct reproduction by subdominant males. (c) 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9933539
TI  - How do cuckoos find their hosts? The role of habitat imprinting.
AB  - Although a number of hypotheses have been proposed for how European cuckoo,
      Cuculus canorus, females may find hosts belonging to their foster parents'
      species, clear evidence is lacking for any of them. Here, we propose 'habitat
      imprinting' as an alternative mechanism for host selection and provide evidence
      that cuckoos are able to remember acquired information about a familiar habitat.
      We hand-reared seven cuckoos in one of five different artificial habitats and
      tested them as adults in habitat choice experiments. In each test habitat, a pair
      of zebra finches, Taeniopygia guttuta, was presented as 'hosts'. We tested
      cuckoos of both sexes because the genotype of males may influence egg colour, and
      therefore egg mimicry; alternatively, habitat imprinting may be a general
      mechanism existing in both sexes but affecting egg mimicry only via females. Test
      cuckoos spent significantly more time looking at their respective familiar
      habitats than at other habitats in 1 of 2 test years. How long cuckoos were
      reared in the artificial habitats correlated positively with how long they spent
      in this habitat during the choice experiments. Additionally, test cuckoos
      remained longer with zebra finches that showed more nest-building behaviour but
      had lower levels of general activity, and they also observed these 'hosts' more
      frequently. If cuckoos choose to breed in habitats resembling those on which they
      were imprinted and search randomly for hosts in these habitats, they would
      increase their probability of parasitizing nests of their foster species. We
      propose that host specificity would be strengthened, however, if cuckoos use a
      sequence of several mechanisms, rather than just one, to find their hosts. (c)
      1998 The Association for the Study of Animal Behaviour.

PMID- 9933540
TI  - Nest building is a sexually selected behaviour in the barn swallow.
AB  - Females may use male nest building to assess male parental quality, and nest size
      would then be a sexually selected trait. In the barn swallow, Hirundo rustica,
      females select their partner by his tail length, a character believed to signal
      good genes. Both sexes participate in nest building, although male participation
      is negatively related to his attractiveness as reflected by tail length. We
      tested the hypothesis that nest building is a sexually selected trait: females
      paired with males of high parental quality (as shown by the male during nest
      building) may obtain a mate providing large amounts of parental investment,
      while, as has been shown previously, females mated to attractive (long-tailed)
      males will acquire mates with good genetic quality. Therefore, since nest
      building in barn swallows occurs after mating, we predicted a postmating sexual
      selection process by which the female invests differentially in reproduction
      depending on the male's nest-building effort (reflecting his willingness to
      invest in reproduction). The volume of material in a nest was related to the
      male's contribution to nest building and, in agreement with our hypothesis, in a
      multiple regression analysis, male tail length and nest material volume were
      negatively related to laying date and positively to female investment in
      reproduction (total number of eggs laid during the breeding season). Moreover,
      females paired with long-tailed males (which contribute very little to nest
      building), but using the same amount of nest material as females paired with
      short-tailed males, reduced the thickness of the nest and hence increased its
      capacity. Therefore, in the barn swallow two different traits appear to be
      sexually selected: tail length of males owing to the good genes process and nest
      building ability owing to the good parent process. (c) 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9933541
TI  - Testing female chaffinch song preferences by operant conditioning.
AB  - Hand-reared female chaffinches, Fringilla coelebs, were tape-tutored just after
      fledging. In the subsequent spring (i.e. their first breeding season) they were
      successfully trained in an operant conditioning task where they could trigger
      song playback by perching on either of two short lever-type perches. In a given
      trial, one of the four songs that had been used for tutoring was paired with a
      song type unknown to the subject. The subjects showed no overall preference for
      either the familiar or unfamiliar song types. In a second experiment one breeding
      season later, the same females were confronted with two versions of one song with
      and without the species-specific terminal flourish. The majority of females
      preferred the version with a terminal flourish. The results of this preliminary
      study suggest that, at least in our small laboratory sample, female chaffinch
      song preferences vary individually for songs within the species-specific range
      and that exposure to a particular song type early in life plays a minor role, if
      any, in forming their preferences. Operant conditioning with song as a reinforcer
      can be used in the laboratory as an alternative method to measures of approach to
      test individual females' song preferences, with the great advantage that the
      control over the stimulus is left with the subject. (c) 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9933542
TI  - Territorial behaviour in the Tasmanian native hen: group and individual
      performance.
AB  - We studied the territorial behaviour of the Tasmanian native hen, Gallinula
      mortierii, a cooperatively breeding gallinule, for three breeding seasons at
      Maria Island National Park, Tasmania, Australia. Our analyses of 2738 territorial
      contests among 54 groups revealed that 87% of interactions were won by the group
      that initiated the interaction, 7% yielded no clear result, and only 6% were won
      by the opposing group. Asymmetries in the resource-holding potential of competing
      groups were not involved in deciding the outcomes of territorial contests. Our
      results suggest that asymmetries in payoff were involved, as in each of the 3
      years groups with better quality territories were more likely to start
      interactions, and as a result, were more likely to win them. Only 6% of
      territorial contests escalated to involve physical contact and changes in
      territory boundaries rarely resulted from individual contests. The quality of a
      group's territory either changed very little between breeding seasons, or
      markedly increased or decreased. We conclude that major changes in territory
      quality occurred only under relatively rare conditions where the risks associated
      with escalated contests were reduced, or where the payoffs from a favourable
      result were improved. Males put more effort into the defence of the group
      territory than did females. The extra effort of males was directed more towards
      extragroup males than towards extragroup females. Females, in contrast, were
      equally aggressive towards both sexes. This suggests that the agonistic behaviour
      of male Tasmanian native hens may contain a mate-guarding component as well as
      functioning in the defence of territory. (c) 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9933543
TI  - Female sexual preferences differ in Mus spicilegus and Mus musculus domesticus:
      the role of familiarization and sexual experience.
AB  - Mating systems correspond to particular ecological conditions and result from
      proximate interactions between individuals. We compared the mating preferences of
      female mice of two species: the house mouse, Mus musculus domesticus, and the
      mound-builder mouse, Mus spicilegus. Because of differences in their habitat, we
      expected to observe differences in their sexual preferences. We studied female
      preferences for a familiar or an unfamiliar male and the occurrence of copulation
      with the unfamiliar male, during two states of female sexual activity: (1) the
      postpartum oestrus of paired females, to evaluate the stability of their sexual
      partnership; and (2) the oestrus of females familiarized with a male, to study
      the mechanisms underlying their sexual preferences. In the polygamous house
      mouse, postpartum oestrous females did not show a clear preference between their
      familiar male and the unfamiliar one. Moreover, oestrous females, familiarized
      with a male (without sexual interactions), preferred an unfamiliar male and
      copulated with him. In contrast, postpartum oestrous females and oestrous females
      of M. spicilegus preferred their familiar male and rarely copulated with the
      unfamiliar male. This study indicates a strong pair bond in established breeding
      pairs in M. spicilegus and shows that this bond can be established by
      familiarization, which is not the case in M. m. domesticus. Our study suggests
      the existence of monogamous traits in M. spicilegus in contrast to the polygamous
      M. m. domesticus. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933544
TI  - The role of calceoli in mate assessment and precopula guarding in Gammarus.
AB  - Gammarid crustacea exhibit precopula mate guarding in which a male will carry a
      potential mate beneath his ventral surface, guarding her for several days until
      she moults and lays her eggs. I investigated the role of the calceoli (bulb-like
      structures on the second antennae) in mate assessment and precopula pairing in
      two Gammarus species by comparing the behaviour of males with and without
      calceoli. Removal of the calceoli had no effect on the pattern of size
      assortative mating, nor did it reduce the number of contacts made per unit time
      between potential mates. However, males without calceoli reduced their assessment
      of potential mates, were less likely to guard a suitable female and guarded for a
      shorter period. These data support the hypothesis that calceoli are used during
      contact assessment to determine a female's intermoult period and hence
      suitability for guarding. (c) 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9933545
TI  - Temporal prey distribution affects the competitive ability of parasitized
      sticklebacks.
AB  - Parasitized animals are often reported to have a reduced competitive ability in
      experimental studies designed to examine foraging success under a specific type
      of competitive interaction; however, since animals compete under a range of
      competition regimes in natural situations, and because success is likely to
      require different foraging skills under each, it is unclear whether infected
      animals should be equally poor competitors under all competitive scenarios. We
      studied the foraging success of three-spined sticklebacks, Gasterosteus
      aculeatus, infected with plerocercoids of a cestode, Schistocephalus solidus, in
      competition with uninfected conspecifics. When pairs of differentially infected
      sticklebacks were presented with sequentially introduced items, the numbers of
      available prey taken by infected and uninfected competitors did not differ
      significantly, although nonparasitized fish were more successful at taking items
      over which there was direct competition. In contrast, when prey items were
      presented simultaneously in a locally dense patch, nonparasitized fish ingested
      significantly more of the available food than their infected counterparts: an
      apparent consequence of their greater ability to take items in rapid succession.
      Our results show that the type of competition conditions generated as a result of
      specific prey distribution patterns plays a role in determining the relative
      foraging success of parasitized sticklebacks, and suggest that this may have
      consequences for the distribution of different infection classes in natural,
      heterogeneous environments. (c) 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9933546
TI  - Behaviour of specialist species in habitat corridors: arboreal dormice avoid
      corridor gaps.
AB  - Linear habitat elements (corridors) may be important for species survival if they
      promote dispersal between fragments of suitable habitat, although there is little
      understanding of the behavioural basis for their use. I conducted experiments to
      determine how the movement of an arboreal habitat specialist species (the
      dormouse, Muscardinus avellanarius) was affected by gaps in corridors (hedgerows)
      and the presence of food resources. Movements in noncorridor habitat were also
      assessed. Translocated dormice were clearly averse to crossing even narrow gaps
      in hedgerows and remained in hedgerows, rather than move into surrounding
      noncorridor habitat. Gaps are thus likely to constrain movement along habitat
      corridors. Dormice travelled further in a hedgerow lacking food resources,
      implying that lack of food may (within an animal's fasting endurance) actually
      promote movement. Although strongly arboreal, dormice were able to locomote
      rapidly through noncorridor habitat (a grass field). Noncorridor habitat thus
      does not represent a complete barrier to movements of at least 100 m. The results
      imply that appropriately managed hedgerows (without gaps) may play an important
      role as corridors in the dispersal of dormice between woodlands. (c) 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9933547
TI  - Chemical mediation of egg dumping in the lace bug Gargaphia solani Heidemann
      (Heteroptera: Tingidae).
AB  - We tested the hypothesis that the proximate cue for egg dumping in the lace bug
      Gargaphia solani Heidemann is a chemical deposited by females on eggs during or
      shortly after oviposition. The results of this study show that: (1) dumping
      frequency declines as eggs age but can be elevated to its highest levels by
      exposure to chemical extracts from young egg masses; and (2) visual cues are not
      necessary to stimulate dumping. Further data support the hypothesis that the
      ovipositional chemical is used by egg dumpers as a long-distance signal of an
      appropriate oviposition site, and is not a mechanism by which guarding females
      relocate their eggs if separated from them. (c) 1998 The Association for the
      Study of Animal Behaviour.

PMID- 9933548
TI  - The risk of sperm competition and the evolution of sperm heteromorphism.
AB  - Members of the Drosophila obscura species group exhibit sperm heteromorphism in
      which males simultaneously produce two different morphologies of sperm, short and
      long. Short sperm represent at least 50% of the ejaculate in several species but
      do not function in fertilization and thus, the evolutionary significance of this
      phenomenon is unknown. Selective pressures associated with the risk of sperm
      competition have been suggested to explain the maintenance of sperm
      heteromorphism. Here I test: (1) whether males alter their behaviour or ejaculate
      characteristics in response to the risk of sperm competition, and (2) whether
      short, nonfertilizing sperm serve as 'cheap filler' in the female reproductive
      tract, thereby delaying female receptivity to subsequent matings. Males did not
      alter tactics based on the risk of sperm competition; copulation durations of
      males mated to nonvirgin females were unexpectedly shorter than when both sexes
      were virgin and, contrary to sperm competition predictions, males did not alter
      the ratio of fertilizing:nonfertilizing sperm relative to female mating status or
      female age. Short sperm had a small, if any, role in influencing female remating
      behaviour. The number and proportion of short sperm present in sperm storage
      organs did not differ between nonvirgin receptive and nonvirgin nonreceptive
      females. The proportion of short sperm present in the ventral receptacle,
      however, was lower in receptive than nonreceptive females. Remating behaviour was
      strongly linked to oviposition patterns. Nonvirgin receptive females oviposited
      more eggs than nonreceptive females, and female remating interval was positively
      related to both the number of eggs and progeny produced. Although, oviposition
      parameters are related to fertilization and thus, the use of long sperm,
      nonvirgin receptive and nonreceptive females did not predictably differ in the
      number or proportion of long sperm in storage. These results suggest oviposition
      per se is probably more important than sperm in determining female receptivity
      and that sperm heteromorphism may play a marginal, if any, role in affecting
      female remating. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933549
TI  - Evoked vocal response in male tungara frogs: pre-existing biases in male
      responses?
AB  - Female tungara frogs, Physalaemus pustulosus, are preferentially attracted to a
      whine-chuck advertisement call over a simple whine (Rand & Ryan 1981, Zeitschrift
      fur Tierpsychologie, 57, 209-214). Females also show phonotactic preferences for
      the whine when a number of other heterospecific or artificial stimuli are added
      to it, and these calls tend to be as attractive to females as a whine-chuck (Ryan
      & Rand 1990, Evolution, 44, 305-314). We tested male tungara frogs with the same
      suite of stimuli using evoked vocal responses as a bioassay to examine sexual
      differences in responses to signal variation. A whine-chuck elicited greater
      responses from males than a whine-only. Artificial and heterospecific stimuli
      that enhanced call attractiveness to females also elicited greater vocal
      responses from males and, as with females, the effects of these stimuli were
      similar to that of the whine-chuck. Thus, in both sexes there are pre-existing
      biases for a suite of stimuli not produced by conspecifics. (c) 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9933550
TI  - A test of the acoustic adaptation hypothesis in four species of marmots.
AB  - Acoustic signals must be transmitted from a signaller to a receiver during which
      time they become modified. The acoustic adaptation hypothesis suggests that
      selection should shape the structure of long-distance signals to maximize
      transmission through different habitats. A specific prediction of the acoustic
      adaptation hypothesis is that long-distance signals of animals in their native
      habitat are expected to change less during transmission than non-native signals
      within that habitat. This prediction was tested using the alarm calls of four
      species of marmots that live in acoustically different habitats and produce
      species-specific, long-distance alarm vocalizations: yellow-bellied marmot,
      Marmota flaviventris; Olympic marmot, M. olympus; hoary marmot, M. caligata; and
      woodchuck, M. monax. By doing so, we evaluated the relative importance the
      acoustic environment plays on selecting for divergent marmot alarm calls.
      Representative alarm calls of the four species were broadcast and rerecorded in
      each species' habitat at four distances from a source. Rerecorded, and therefore
      degraded alarm calls, were compared to undegraded calls using spectrogram
      correlation. If each species' alarm call was transmitted with less overall
      degradation in its own environment, a significant interaction between species'
      habitat and species' call type would be expected. Transmission fidelity at each
      of four distances was treated as a multivariate response and differences among
      habitat and call type were tested in a two-way MANOVA. Although significant
      overall differences in the transmission properties of the habitats were found,
      and significant overall differences in the transmission properties of the call
      types were found, there was no significant interaction between habitat and call
      type. Thus, the evidence did not support the acoustic adaptation hypothesis for
      these marmot species. Factors other than maximizing long-distance transmission
      through the environment may be important in the evolution of species-specific
      marmot alarm calls. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933551
TI  - Proximate and ultimate causes of adoption in ring-billed gulls.
AB  - From 1987 to 1994, the annual frequency of adoption by breeding pairs at a Lake
      Erie ring-billed gull, Larus delawarensis, colony ranged from 3 to 37% (average
      8%/year, N=7 years) and, on average, foster parents raised 0.5 fewer of their own
      chicks to fledging than pairs that did not adopt. The key evolutionary question
      is: why do some individuals apparently suffer the costs associated with a
      behaviour that appears to enhance the fitness of others? From 1992 to 1995, I
      investigated the proximate and ultimate causes of adoption in ring-billed gulls
      from the perspectives of both the foster parents and adopted chicks, and tested
      predictions that differentiated between various competing adaptive and
      nonadaptive hypotheses that have been proposed to explain it. While I was able to
      demonstrate a breeding cost, I failed to identify any benefits to foster parents.
      Thus, the adaptive hypotheses that rely on the foster parents benefiting were not
      supported (e.g. kin selection, reciprocal altruism, acquisition of parenting
      experience). From the foster parent's perspective, adoption was mediated through
      errors in parent-offspring recognition. Under natural conditions, most fostering
      pairs were tending small chicks (<6 days old) at the time of adoptions; in chick
      transfer experiments, resident parents did not discriminate against foreign
      chicks until their own chicks were 7-9 days old. Chicks (N=25) that subsequently
      abandoned their natal nests were lighter, and grew at a slower rate, than chicks
      that survived to fledging in their home broods. Thus, departing chicks were at a
      survival disadvantage in their home broods. Chicks that gained acceptance into
      foreign broods where they were older/larger than the resident chicks realized
      high survival at the expense of their foster siblings and parents. Based upon
      individual growth rates and the corresponding survival probabilities,
      disadvantaged chicks approximately doubled their survival chances through foster
      care. Why has selection not eliminated adoption? I argue that adoption is an
      evolutionary arms race between the two principle actor groups; disadvantaged
      chicks, which benefit through foster care, and host parents, which avoid
      providing foster care (e.g. infanticide). In ring-billed gulls, selection has
      failed to eliminate adoption because the long-term reproductive cost (estimated
      at 4%, this study) of an occasional adoption is probably offset by the relatively
      higher costs associated with stricter kin discrimination mechanisms (e.g.
      parental infanticide). (c) 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9933552
TI  - Butting by calves, Bos taurus, and rate of milk flow.
AB  - During nursing, the young of many ungulates butt at their dams' udder, which has
      been hypothesized to reflect difficulty obtaining milk. We investigated the
      effect of manipulating milk flow rate on the butting behaviour of domestic calves
      sucking milk from an artificial teat. The lowest rate of butting during nutritive
      sucking occurred with the fastest flow rate, and the highest rate of butting
      occurred with the slowest flow rate. When milk flow rate was changed during a
      meal, calves butted more following a decrease in flow rate than following an
      increase in flow rate. Butting rates were consistent and relatively low with a
      constant flow of milk. Regardless of flow rate, calves butted more at the
      beginning of their meal compared with the middle and end. Overall, the highest
      butting rate occurred when milk flow stopped, either at the end of the meal or
      when milk flow during the meal was stopped repeatedly for 30-s periods. We
      conclude that calves are sensitive to variations in milk flow rate and that
      butting rate changes accordingly. The occurrence of butting by young ungulates
      during nursing thus may indicate either a stoppage of milk flow or a decrease in
      milk flow rate, and thus may help identify periods of nonnutritive sucking during
      nursing. (c) 1998 The Association for the Study of Animal Behaviour.

PMID- 9933553
TI  - Individual recognition and memory in lobster dominance.
AB  - American lobsters, Homarus americanus, form stable dominance relationships in
      captivity. Size, sex and stage in the moult cycle are important determinants for
      dominance. Other factors, such as recent agonistic experience play a role. This
      paper investigates how lobsters maintain their stable dominance relationships:
      they may recognize individuals or alternatively, recognize overall dominance
      status. We paired lobsters in two consecutive 'boxing matches'. Results indicate
      that lobsters remember familiar opponents when kept either in isolation or in
      communal tanks for 24 h between their first and second fights. Subordinates
      immediately backed away from familiar dominants, avoiding a second fight. In some
      animals, this memory lasted between 1-2 weeks if pairs were kept separate between
      the first and second fights. When paired for the second fight against unfamiliar
      dominant lobsters, subordinate lobsters from first fights actively fought and won
      the encounter. These results suggest that lobsters are capable of 'individual
      recognition'. In nature, the observed social organization of lobsters may be
      maintained by individual recognition of a small number of residents inhabiting
      separate, nearby shelters. (c) 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9933554
TI  - The biological basis of grooming in moose: programmed versus stimulus-driven
      grooming.
AB  - In domestic and wild mammals, tick infestation can be a significant fitness cost.
      Grooming behaviour has been shown to be effective in removing ticks. We studied
      grooming by moose, Alces alces, infested with winter ticks, Dermacentor
      albipictus, to determine which of two nonexclusive models for the regulation of
      tick-removal grooming, programmed or stimulus driven, best fit this host-parasite
      relationship. The programmed grooming model states that most grooming is driven
      by an internal timing mechanism which periodically evokes a bout a grooming
      independent of peripheral stimulation from tick bites. Because programmed
      grooming is preventive, the model predicts that those animals that groom the most
      will carry the fewest ticks, and a baseline level of programmed grooming is
      predicted even in a tick-sparse or tick-free environment. The stimulus-driven
      grooming model, on the other hand, states that grooming is a direct response to
      cutaneous irritation caused by tick bites and other sources of irritation. This
      stimulus-driven model predicts that (1) animals showing the highest rate of
      grooming will carry the most ticks and (2) animals will groom little when tick
      challenge is low. Both predictions of the stimulus-driven model were supported
      for moose: (1) calves oral-groomed three times more than cows, and tick densities
      on calves were three times higher than on cows; and (2) although all moose
      carried high densities of immature winter ticks (larvae, nymphs) from October
      through to February, grooming rate was very low until adult ticks started feeding
      in March-April. Peak grooming rates occurred during adult tick engorgement in
      March-April. Because an engorging adult female tick produces far more irritation
      than an engorging nymphal or larval tick, moose appeared to groom in direct
      proportion to the degree of cutaneous irritation and did not show a baseline
      level of grooming. The predominance of stimulus-driven grooming and apparent
      absence of programmed grooming may be the result of relaxed selection pressure
      for grooming in the evolutionary history of moose. Because the winter tick
      appears to have been introduced to moose from deer relatively recently, moose may
      not have had the time to adapt to winter ticks. The coevolutionary relationship
      between moose and winter ticks may be of insufficient duration for the evolution
      and/or maintenance of programmed grooming. (c) 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9933555
TI  - Reanalysis gives further support to the 'shotgun' model of shiny cowbird
      parasitism of house wren nests.

PMID- 9933558
TI  - Editors' Acknowledgements.

PMID- 9933559
TI  - Contents of Volume 56.

PMID- 9933560
TI  - A human mitochondrial DNA standard reference material for quality control in
      forensic identification, medical diagnosis, and mutation detection.
AB  - A human mitochondrial DNA (mtDNA) standard reference material (SRM 2392) will
      provide quality control when mtDNA is sequenced for forensic identifications,
      medical diagnosis, or mutation detection. SRM 2392 includes DNA from two
      lymphoblast cell cultures (CHR and 9947A) and cloned DNA from the CHR HV1 region,
      which contains a C stretch and is difficult to sequence. The mtDNA sequence (but
      not the DNA) of a third human template GM03798 is provided for comparison. Fifty
      eight unique primer sets allow any area or the entire mtDNA (16,569 bp) to be
      amplified and sequenced. While none of the differences in these three templates
      correspond to published mutations associated with specific diseases, some of
      these differences did result in animo acid changes compared with that published
      by S. Anderson et al. (1981, Nature 290: 457-465). An interlaboratory evaluation
      of the amplification, sequencing, and data analysis of the CHR template was
      conducted by four laboratories. Corroboration of the SRM results will provide
      quality assurance that any unknown mtDNA is also being amplified and sequenced
      correctly.

PMID- 9933561
TI  - Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in
      mice.
AB  - The genetic basis for differential sensitivity of inbred mice to inflammatory
      bowel disease induced by dextran sulfate sodium (DSS) is unknown. Susceptible
      C3H/HeJ were outcrossed to partially resistant C57BL/6J mice. F2 and N2 progeny
      were phenotyped by evaluating histopathologic lesions in large intestine detected
      16 days after a 5-day period of feeding 3.5% DSS. Screening for DSS colitis
      (Dssc) loci revealed quantitative trait loci (QTL) on Chr 5 (Dssc1) and Chr 2
      (Dssc2). These traits contributed additively, explaining 17.5% of the variation
      in total colonic lesions. Additional QTL on Chr 18 and 1 that collectively
      explained 11% of the variation in total colon lesions were indicated. In the
      cecum, only a putative QTL on Chr 11 was associated with pathology (lesion
      severity) in the cecum. Reduced DSS susceptibility was observed in congenic
      stocks in which the highly susceptible NOD/Lt strain carried putative resistance
      alleles from either B6 on Chr 2 or from the highly resistant NON/Lt strain on Chr
      9. We conclude that multiple genes control susceptibility to DSS colitis in mice.
      Possible Dssc candidate genes are discussed in terms of current knowledge of
      inflammatory bowel disease susceptibility loci in humans.

PMID- 9933562
TI  - TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to
      the region of chromosome 1p31 that is frequently deleted in sporadic breast
      cancer.
AB  - The 1p31 region shows loss of heterozygosity in up to 50% of human breast
      cancers, indicating the presence of a tumor suppressor gene in this location. We
      have mapped six novel ESTs to a 15-Mb contig of yeast artificial chromosomes
      spanning the critical region of 1p31. One of these ESTs was localized within the
      contig to the region most commonly undergoing loss of heterozygosity in breast
      cancer. The corresponding gene sequence for this EST was established by cDNA
      cloning and RACE procedures. This gene is 2 kb long and contains a
      tetratricopeptide repeat motif and a coiled-coil domain. This family of genes has
      been implicated in a wide variety of functions, including tumorigenesis. This is
      the fourth member of the human gene family, and so we have named this gene TTC4.
      Northern blot analysis demonstrates a ubiquitous pattern of gene expression that
      includes breast tissue. A preliminary screen of human breast cancer cell lines
      shows that TTC4 is expressed in all cases, but SSCP analysis of the coding region
      of this gene following RT-PCR failed to reveal any mutations. Clearly, because of
      its map location, a more extensive analysis is warranted to establish whether
      subtle mutations are present in breast cancers.

PMID- 9933563
TI  - A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5
      and genes in the LOH11A metastasis suppressor region.
AB  - The centromeric part of chromosome segment 11p15.5 contains a region of frequent
      allele loss in many adult solid malignancies. This region, called LOH11A, is lost
      in 75% of lung cancers and is thought to contain a gene that may function as a
      metastasis suppressor. Genetic complementation studies have shown suppression of
      the malignant phenotype including reduction of metastasis formation. We
      constructed a high-resolution physical map and contig over 1.4 Mb that includes
      the beta-hemoglobin gene cluster and the gene for the large subunit of
      ribonucleotide reductase (RRM1). Through sequencing and computerized analysis, we
      determined that this region contains an unusually large number of transposable
      elements, which suggests that double-stranded DNA breaks occur frequently here.
      Twenty-two putative genes were identified. Because of its location at the site of
      maximal allele loss in the 650-kb LOH11A region and previous functional studies,
      RRM1 is the most likely candidate gene with metastasis suppressor function. The
      malignant phenotype, in this case, results from a relative loss of function
      rather than a complete loss.

PMID- 9933565
TI  - Physical delineation of a 700-kb region overlapping the Looptail mutation on
      mouse chromosome 1.
AB  - The mouse looptail (Lp) mutation is an established model for neural tube defects
      with homozygous Lp embryos showing an open neural tube from the caudal midbrain
      to the tip of the tail. Heterozygous Lp mice are characterized by a "looped-tail"
      and wobbly head movements. The Lp gene has been mapped to a 0.6-cM interval on
      mouse chromosome 1 delineated by two clusters of markers,
      Fcer1gamma/Usf1/D1Mit113/D1Wsu1 on the proximal side and
      Fcer1alpha/Spna1/D1Mit149 distally. In the present study, we have created a high
      resolution physical map of the Lp genetic interval that is based on long-range
      restriction mapping by PFGE, fluorescence in situ hybridization analysis of
      interphase nuclei and extended chromatid fibers, and the assembly of a cloned
      contig. This contig consists of 25 independent and overlapping BAC clones and 3
      YAC clones. The combined analysis indicates that the 0.6-cM genetic interval for
      Lp corresponds to a minimal physical interval of 700 kb that is delineated by
      D1Mit113 proximally (two crossovers) and Fcer1alpha distally (one crossover). The
      overall gene order and intergene distances for the region were determined to be
      D1Mit113-<150 kb-Nhlh1-250 kb-Atp1alpha2-280 kb-Fcer1alpha. Partial sequencing of
      BAC clones from the contig yielded 42 new STS markers for this region of mouse
      chromosome 1. Sequence analysis of the BAC clones and assignment of ESTs from the
      human transcript map to the cloned contig allowed the placement of four new
      transcription units within this region: Pc326, Kiaa0253, and Pea15 were
      positioned in the Nhlh1/Atp1alpha2 nonrecombinant interval, while Girk3 was
      located distal to Atp1alpha2.

PMID- 9933564
TI  - A new family of mouse genes homologous to the human MAGE genes.
AB  - The human MAGE genes are expressed in a wide variety of tumors but not in normal
      cells, with the exception of the male germ cells, placenta, and, possibly, cells
      of the developing embryo. These genes encode tumor-specific antigens recognized
      by cytolytic T lymphocytes. The MAGE genes are located on the X chromosome, in
      three clusters denoted MAGE-A, B, and C, mapping at q28, p21.3, and q26,
      respectively. The function of these genes remains unknown. Because mice offer
      many advantages for the study of genes that may be involved in embryonic
      development, we looked for the murine equivalents of the 12 human MAGE-A genes.
      Using a MAGE-A probe, we isolated 8 new murine genes that are homologous to the
      MAGE genes. On average, the open reading frames (ORFs) of these 8 closely related
      genes display a slightly higher degree of nucleotide identity with the MAGE-A
      ORFs than with the MAGE-B or MAGE-C ORFs. Furthermore, like MAGE-A genes, they
      encode acidic proteins, whereas the MAGE-B genes encode basic proteins.
      Accordingly, these 8 murine genes were named Mage-a1 to 8 (approved symbols
      Magea1 to 8). Mage-a genes were mapped in two different loci on the mouse X
      chromosome. Mage-a4 and Mage-a7 are located in a region that is syntenic to
      either Xp21 or Xq28. The 6 other genes are arranged in a cluster located in a
      region syntenic to Xp22. Like their human counterparts, Mage-a genes were found
      to be transcribed in adult testis, but not in other tissues. Expression of some
      Mage-a genes was also detected in tumor cell lines. Two Mage-a genes were found
      to be expressed in blastocysts.

PMID- 9933566
TI  - A direct repeat sequence at the Rasgrf1 locus and imprinted expression.
AB  - Genomic imprinting is an epigenetic modification that can lead to parental
      specific monoallelic expression of specific autosomal genes. While methylation of
      CpG dinucleotides is thought to be a strong candidate for this epigenetic
      modification, little is known about the establishment or maintenance of parental
      origin-specific methylation patterns. We have recently identified a portion of
      mouse chromosome 9 containing a paternally methylated region associated with a
      paternally expressed imprinted gene, Ras protein-specific guanine nucleotide
      releasing factor 1 (Rasgrf1). This area of chromosome 9 also contains a short,
      direct tandem repeat in close proximity to a paternally methylated NotI site 30
      kb upstream of Rasgrf1. Short, direct tandem repeats have been found associated
      with other imprinted genes and may act as important regulatory structures. Here
      we demonstrate that two rodent species (Mus and Rattus) contain a similar direct
      repeat structure associated with a region of paternal-specific methylation. In
      both species, the Rasgrf1 gene shows paternal-specific monoallelic expression in
      neonatal brain. A more divergent rodent species (Peromyscus) appears to lack a
      similar repeat structure based on Southern Blot analysis. Peromyscus animals show
      biallelic expression of Rasgrf1 in neonatal brain. These results suggest that
      direct repeat elements may play an important role in the imprinting process.

PMID- 9933567
TI  - Genomic organization, fine-mapping, and expression of the human islet-brain 1
      (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene.
AB  - Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat,
      is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK).
      Whether IB1 and JIP-1 are present in humans was not known. We report the sequence
      of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the
      human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94%
      identical to rat IB1. The tissue-specific expression of IB1 in human is similar
      to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome
      11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an
      IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found
      in the human genome. Our data indicate that the sequence and expression pattern
      of IB1 are highly conserved between rodent and human and provide the necessary
      tools to investigate whether IB1 is involved in human diseases.

PMID- 9933568
TI  - Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a
      conserved cluster of three organic cation transporters on mouse chromosome 17 and
      human 6q26-q27.
AB  - Here we report the isolation of the mouse and human solute carrier genes
      Slc22a3/SLC22A3. Slc22a3 is specifically expressed in placenta, but the levels of
      expression decline toward the end of gestation. A BAC contig spanning the mouse
      Slc22a3 gene was constructed, and Slc22a3 was mapped between the Igf2r and Plg
      genes in close association with two additional members of the Slc22a gene family,
      mouse Slc22a1 and Slc22a2. A partial cDNA sequence of the human SLC22A3 gene was
      reconstituted from sequenced EST clones. SLC22A3 is expressed in first-trimester
      and term placenta, but also in skeletal muscle, prostate, aorta, liver, fetal
      lung, salivary gland, and adrenal gland. Using a somatic cell hybrid panel and a
      human YAC clone, SLC22A3 was mapped to the syntenic region on human chromosome
      6q26-q27, between the IGF2R and APO(a)-like genes. SLC22A1 and SLC22A2 localized
      to the same locus, demonstrating the conservation of the close physical linkage
      of these three organic cation transporter genes in mouse and human.

PMID- 9933569
TI  - Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle
      checkpoint control gene.
AB  - The Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene is
      required for S-phase and G2/M arrest in response to both DNA damage and
      incomplete DNA replication. We isolated and characterized the putative human
      (RAD17Sp) and mouse (mRAD17Sp) homologs of the S. pombe Rad17 (Rad17Sp) protein.
      The human RAD17Sp open reading frame (ORF) encodes a protein of 681 amino acids;
      the mRAD17Sp ORF codes for a protein of 688 amino acids. The mRAD17Sp messenger
      is highly expressed in the testis as a single 3-kb mRNA species. The human
      RAD17Sp and mRAD17Sp proteins are 24% identical and 46% similar to the S.pombe
      Rad17Sp protein. Sequence homology was also noted with the Saccharomyces
      cerevisiae Rad24Sc (which is the structural counterpart of S.pombe Rad17Sp) and
      structurally related polypeptides from Caenorhabditis elegans, Arabidopsis
      thaliana, Pyrococcus horikoshii, and Drosophila melanogaster. The degree of
      conservation between the mammalian RAD17Sp proteins and those of the other
      species is consistent with the evolutionary distance between the species,
      indicating that these proteins are most likely true counterparts. In addition,
      homology was found between the Rad17Sp homologs and proteins identified as
      components of mammalian replication factor C (RF-C)/activator 1, especially in
      several highly conserved RF-C-like domains including a "Walker A" motif. Using
      FISH and analysis of a panel of rodent-human cell hybrids, the human RAD17Sp gene
      (HGMW-approved symbol RAD17 could be localized on human chromosome 5q13-q14, a
      region implicated in the etiology of small cell lung carcinoma, non-small-cell
      lung carcinoma, duodenal adenocarcinoma, and head and neck squamous cell
      carcinoma. Our results suggest that the structure and function of the checkpoint
      "rad" genes in the G2/M checkpoint pathway are evolutionary conserved between
      yeast and higher eukaryotes.

PMID- 9933570
TI  - Structural organization and expression patterns of the human and mouse genes for
      the type I procollagen COOH-terminal proteinase enhancer protein.
AB  - The procollagen C-proteinase enhancer (PCPE) is a glycoprotein that potentiates
      enzymatic cleavage of the type I procollagen C-propeptide by bone morphogenetic
      protein-1 (BMP-1). The human PCPE gene (PCOLCE) was previously mapped to 7q22, an
      area frequently disrupted in uterine leiomyomata, while disruption of the rat
      PCPE gene leads to anchorage-independent growth and loss of contact inhibition in
      rat fibroblasts. Here we describe the entire intron/exon organizations of PCOLCE
      and the mouse PCPE gene (Pcolce) and analyze expression of PCOLCE RNA in various
      human adult and fetal tissues and of Pcolce RNA at various stages of mouse
      development. PCOLCE and Pcolce are shown to be small genes 6.0 and 6.5 kb,
      respectively, with a conserved intron/exon structure comprising 9 exons. A
      notable difference between the two genes derives from insertion of multiple Alu
      sequences immediately upstream and downstream and within PCOLCE. Temporal
      expression of PCPE mRNA is shown to differ from that of BMP-1 and type I
      procollagen during mouse development, consistent with possible additional
      functions for PCPE beyond enhancement of C-proteinase activity. Consistent with a
      possible role in leiomyomata, PCOLCE is shown to be expressed at relatively high
      levels in uterus.

PMID- 9933571
TI  - Localization of the gene coding for ROCK II/Rho kinase on human chromosome 2p24.
AB  - Serine/threonine kinase ROCK II/Rho kinase, which is an isozyme of ROCK I, is one
      of the targets for the small GTPase Rho. ROCK II regulates the formation of actin
      stress fibers and focal adhesions, cytokinesis, smooth muscle contraction, and
      the activation of c-fos serum response element. To elucidate the role of ROCK II
      in human disease, we have cloned a 4363-bp cDNA encoding human ROCK II.
      Sequencing analysis has shown that human ROCK II contains 1388 amino acid
      residues with a calculated molecular mass of approximately 161 kDa. Fluorescence
      in situ hybridization analysis showed that the human ROCK II gene is located on
      chromosome 2p24. Radiation hybrid mapping has shown that the human ROCK II gene
      is located very close to the highly polymorphic marker D2S359.

PMID- 9933572
TI  - The human TBX6 gene: cloning and assignment to chromosome 16p11.2.
AB  - Tbx6 is a member of the T-box family of proteins, which share a region of
      homology corresponding to the DNA-binding domain of the transcription factor T.
      Previous expression studies and knockout experiments in mice indicate that Tbx6
      is important for specification of paraxial mesoderm structures. We have isolated
      and characterized the human orthologue, TBX6. Sequence comparisons show that
      overall the nucleotide homology between human and mouse TBX6/Tbx6 is 84%; within
      the T-box there is 89% nucleotide homology and 96% amino acid identity. TBX6 maps
      to chromosome 16 p11.2, a region syntenic with mouse chromosome 7, at 61 cM, the
      map position of mouse Tbx6. RT-PCR studies of RNA distribution indicate that this
      gene is expressed not only during gastrulation but has a second phase of
      expression in some adult tissues including testis. DNA/protein-binding studies
      demonstrate that Tbx6 binds to the same target DNA as T protein and can form a
      dimeric complex with DNA. We could find no evidence that Tbx6 forms a heterodimer
      with T.

PMID- 9933573
TI  - Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that
      contains the Nijmegen breakage syndrome gene, NBS1.
AB  - An 800-kb region on chromosome 8q21, which complements the phenotype of cells
      from Nijmegen breakage syndrome patients, is a candidate for the locus of the
      underlying gene, termed NBS1. The sequence of this 800-kb region of DNA indicated
      that the size of this segment is 755,832 bp with an additional 36-kb gap. From
      this region, we identified four genes including NBS1, a gene coding for a 27-kDa
      vitamin D-dependent calcium-binding protein (27-kDa calbindin), the mitochondrial
      2,4-dienoyl-CoA reductase gene, and a novel gene, C8orf1/hT41. All four genes
      were aligned in a 250-kb centromeric portion of the region, and no gene was found
      in the remaining telomeric portion containing 500 kb. The genomic organization of
      the C8orf1/hT41 and NBS1 genes has been analyzed using the computer programs
      GRAIL 2 and GENSCAN. They predicted and successfully found more than 93% of the
      exons, even a small 54-bp exon, indicating that one or more exons in any gene can
      be identified by these programs. GENSCAN was more efficient at locating the four
      genes than GRAIL 2 and identified 15 of the 16 exons of the NBS1 gene. This 800
      kb region contained repetitive sequences, including 179 copies of the Alu
      sequence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107
      copies of the LTR sequence (1 copy/7.1 kb), and 63 copies of the MER sequence (1
      copy/12 kb). There was a slight but not significant difference in the repetitive
      content of the gene-rich region and the remaining noncoding region. Our results
      indicate that computer-assisted methods are useful and powerful for identifying
      exons of both known and novel genes.

PMID- 9933574
TI  - Assignment of the melatonin-related receptor to human chromosome X (GPR50) and
      mouse chromosome X (Gpr50).
AB  - Recent efforts to clone further members of the melatonin receptor family have led
      to the identification of a novel G-protein-coupled receptor in human pituitary.
      This receptor, referred to as H9, is clearly related to high-affinity melatonin
      receptors yet unable to bind this hormone. We now report the cloning and
      expression of the cDNA encoding the H9 receptor in mice. The mouse clone encodes
      a protein of 591 amino acids that shares 74% amino acid identity with the human
      receptor and is unable to bind 2-[125I]iodomelatonin when transiently expressed
      in COS-7 cells. We also determined the chromosome loci of the human and mouse H9
      receptor genes. Both genes were found to be X-linked: radiation hybrid mapping
      revealed that the human H9 gene (GPR50) is localized to Xq28. The mouse gene
      (Gpr50) was determined to lie in the proximal portion of chromosome X by means of
      interspecific backcross analysis. These loci might be relevant to genetically
      based neuroendocrine disorders.

PMID- 9933575
TI  - Human (DACH) and mouse (Dach) homologues of Drosophila dachshund map to
      chromosomes 13q22 and 14E3, respectively.

PMID- 9933576
TI  - Assignment of the human gene for endosarcomeric cytoskeletal M-protein (MYOM2) to
      8p23.3.

PMID- 9933577
TI  - Evidence that a phosphatidylinositol 3,4,5-trisphosphate-binding protein can
      function in nucleus.
AB  - PIP3BP is a phosphatidylinositol 3,4,5-trisphosphate-binding protein (PIP3BP)
      abundant in brain, containing a zinc finger motif and two pleckstrin homology
      (PH) domains. Staining of rat brain cells with anti-PIP3BP antibody and
      determination of localization of PIP3BP fused to the green fluorescent protein
      (GFP-PIP3BP) revealed that PIP3BP was targeted to the nucleus. Targeting was
      dependent on a putative nuclear localization signal in PIP3BP. Generation of PIP3
      in the nucleus was detected in H2O2-treated 293T cells, nerve growth factor (NGF)
      treated PC12 cells, and platelet-derived growth factor (PDGF)-treated NIH 3T3
      cells. Translocation of phosphatidylinositol 3-kinase (PI 3-kinase) to the
      nucleus and enhanced activity of PI 3-kinase in the nucleus fraction were
      observed after H2O2 treatment of 293T cells, suggesting that PI 3-kinase can be
      activated in the nucleus as well as in the membrane after appropriate stimulation
      of the cells. Co-expression of the constitutively active PI 3-kinase with PIP3BP
      resulted in exportation of the protein from the nucleus to the cytoplasm,
      suggesting that PIP3BP can function as a PIP3-binding protein in the intact
      cells. These results imply that there may be an unknown function of PI 3-kinase
      in the nucleus.

PMID- 9933578
TI  - The in vitro ligation of bacterially expressed proteins using an intein from
      Methanobacterium thermoautotrophicum.
AB  - The smallest known intein, found in the ribonucleoside diphosphate reductase gene
      of Methanobacterium thermoautotrophicum (Mth RIR1 intein), was found to splice
      poorly in Escherichia coli with the naturally occurring proline residue adjacent
      to the N-terminal cysteine of the intein. Splicing proficiency increased when
      this proline was replaced with an alanine residue. However, constructs that
      displayed efficient N- and C-terminal cleavage were created by replacing either
      the C-terminal asparagine or N-terminal cysteine of the intein, respectively,
      with an alanine. Furthermore, these constructs were used to specifically generate
      complementary reactive groups on protein sequences for use in ligation reactions.
      Reaction between an intein-generated C-terminal thioester on E. coli maltose
      binding protein (43 kDa) and an intein-generated cysteine at the N terminus of
      either T4 DNA ligase (56 kDa) or thioredoxin (12 kDa) resulted in the ligation of
      the proteins through a native peptide bond. Thus the smallest of the known
      inteins is capable of splicing and its unique properties extend the utility of
      intein-mediated protein ligation to include the in vitro fusion of large,
      bacterially expressed proteins.

PMID- 9933580
TI  - Direct photoaffinity labeling of the Kir6.2 subunit of the ATP-sensitive K+
      channel by 8-azido-ATP.
AB  - ATP-sensitive potassium channels are under complex regulation by intracellular
      ATP and ADP. The potentiating effect of MgADP is conferred by the sulfonylurea
      receptor subunit of the channel, SUR, whereas the inhibitory effect of ATP
      appears to be mediated via the pore-forming subunit, Kir6.2. We determined
      whether ATP directly interacts with a binding site on the Kir6.2 subunit to
      mediate channel inhibition by analyzing binding of a photoaffinity analog of ATP
      (8-azido-[gamma-32P]ATP) to membranes from COS-7 cells transiently expressing
      Kir6.2. We demonstrate that Kir6.2 can be directly labeled by 8-azido-[gamma
      32P]ATP but that the related subunit Kir4.1, which is not inhibited by ATP, is
      not labeled. Photoaffinity labeling of Kir6.2 is reduced by approximately 50%
      with 100 microM ATP. In addition, mutations in the NH2 terminus (R50G) and the
      COOH terminus (K185Q) of Kir6.2, which have both been shown to reduce the
      inhibitory effect of ATP upon Kir6.2 channel activity, reduced photoaffinity
      labeling by >50%. These results demonstrate that ATP binds directly to Kir6.2 and
      that both the NH2- and COOH-terminal intracellular domains may influence ATP
      binding.

PMID- 9933579
TI  - Protein kinase Ciota activity is necessary for Bcr-Abl-mediated resistance to
      drug-induced apoptosis.
AB  - K562 chronic myelogenous leukemia cells are highly resistant to chemotherapeutic
      drugs, such as taxol, that induce cell death by apoptosis. This resistance is
      mediated by the chimeric tyrosine kinase oncogene Bcr-Abl. However, little is
      known about the mechanism by which Bcr-Abl protects K562 cells from apoptosis. We
      recently demonstrated that expression of PKCiota is necessary for the resistance
      of K562 cells to taxol-induced apoptosis (Murray, N. R., and Fields, A. P. (1997)
      J. Biol. Chem. 272, 27521-27524). We now demonstrate that treatment of K562 cells
      with taxol leads to sustained activation of PKCiota. In contrast, Bcr-Abl
      negative HL60 myeloid leukemia cells, which are sensitive to taxol-induced
      apoptosis, do not exhibit sustained PKCiota activation in response to taxol.
      Treatment of K562 cells with tyrphostin AG957, a selective Bcr-Abl inhibitor,
      blocks taxol-induced PKCiota activation and sensitizes these cells to taxol
      induced apoptosis, indicating that PKCiota is a relevant downstream target of Bcr
      Abl-mediated resistance. Furthermore, expression of constitutively active PKCiota
      by adenovirus-mediated gene transfer rescues AG957-treated K562 cells from taxol
      induced apoptosis. Taken together, these results demonstrate that both Bcr-Abl
      and PKCiota activity are necessary for apoptotic resistance in K562 cells.
      Furthermore, they identify PKCiota as a critical downstream target of Bcr-Abl
      that is sufficient to mediate the anti-apoptotic effects of Bcr-Abl.

PMID- 9933581
TI  - The nicotinic alpha4 receptor subunit contributes to the lining of the ion
      channel pore when expressed with the 5-HT3 receptor subunit.
AB  - To understand the wide variation of calcium permeability seen in native and
      recombinant 5-HT3 receptor (5-HT3R) channels, we reported previously the novel
      hypothesis that the serotonin 5-HT3R subunit can co-assemble with the alpha4
      subunit of the nicotinic acetylcholine receptor (van Hooft, J. A., Spier, A. D.,
      Yakel, J. L., Lummis, S. C. R. & Vijverberg, H. P. M. (1998) Proc. Natl. Acad.
      Sci. U. S. A. 95, 11456-11461). To test the hypothesis that the alpha4 subunit
      contributes to the lining of the pore of the resulting 5-HT3R channel, a mutant
      nicotinic alpha4 subunit with a reactive cysteine residue engineered into the
      putative pore region was constructed by substituting the leucine at position 285
      (alpha4-L285C). The sulfhydryl-modifying reagent [2-(trimethylammonium)
      ethyl]methanethiosulfonate (MTSET) reduced the acetylcholine-induced current in
      oocytes expressing this mutant nicotinic alpha4-L285C subunit along with the
      nicotinic beta2 subunit by approximately 60%. When the alpha4-L285C subunit was
      co-expressed with the 5-HT3R subunit, both MTSET and silver nitrate (AgNO3),
      another cysteine-modifying reagent, significantly reduced the serotonin-induced
      current. No reduction was seen when the 5-HT3R was expressed alone or with the
      wild-type alpha4 subunit. These data provide direct molecular evidence that the
      nicotinic alpha4 subunit co-assembles with the 5-HT3R subunit and forms an
      integral part of the ion channel pore.

PMID- 9933583
TI  - Mitochondrial citrate synthase is immobilized in vivo.
AB  - The enzymes of the tricarboxylic acid cycle in the mitochondrial matrix are
      proposed to form a multienzyme complex, in which there is channeling of
      substrates between enzyme active sites. However no direct evidence has been
      obtained in vivo for the involvement of these enzymes in such a complex. We have
      labeled the tricarboxylic acid cycle enzyme, citrate synthase 1, in the yeast
      Saccharomyces cerevisiae, by biosynthetic incorporation of 5-fluorotryptophan.
      Comparison of the 19F NMR resonance intensities from the labeled enzyme in the
      intact cell and in cell-free lysates indicated that the enzyme is motionally
      restricted in vivo, consistent with its participation in a multienzyme complex.

PMID- 9933582
TI  - The human homologue of Drosophila TRF-proximal protein is associated with an RNA
      polymerase II-SRB complex.
AB  - Mammalian RNA polymerase II holoenzymes are large complexes that have been
      reported to contain, in addition to RNA polymerase II, homologues of several
      yeast SRBs, various general transcription factors, and other polypeptides. On the
      basis of its copurification with an SRB-containing RNA polymerase II complex by
      conventional chromatography procedures, we have identified a human homologue of
      Drosophila TRF-proximal protein, designated hTRFP, and isolated its cognate cDNA.
      Antibody specific for SRB7 can immunoprecipitate hTRFP and RNA polymerase II and,
      reciprocally, antibody specific for hTRFP can immunoprecipitate RNA polymerase II
      and SRB7. These data indicate that hTRFP is an integral component of an RNA
      polymerase II-SRB complex. Whereas the precise function of hTRFP remains to be
      determined, the hTRFP-containing RNA polymerase II-SRB complex supports basal
      level transcription and, relative to RNA polymerase II alone, enhances
      transcriptional activation by Gal4-VP16 in the presence of cofactor PC4. Thus,
      hTRFP may regulate transcription of class II genes through association with the
      RNA polymerase II-SRB complex.

PMID- 9933584
TI  - beta-subunit of nuclear pore-targeting complex (importin-beta) can be exported
      from the nucleus in a Ran-independent manner.
AB  - The nuclear export of importin-alpha is mediated by CAS, which is related to
      importin-beta, whereas the mechanism for the export of importin-beta remains
      unclear. In this study, we demonstrate that the nuclear export of importin-beta
      is mediated by the nuclear pore complex-binding domain of this molecule.
      Insensitivity to leptomycin B indicates that its export is not mediated by a
      leucine-rich nuclear export signal-specific receptor, CRM1. Furthermore, the
      nuclear export of importin-beta was not inhibited by co-injection with a GTPase
      deficient Ran mutant (G19V). The cell line tsBN2 contains a temperature-sensitive
      point mutation in the RCC1 gene, which encodes a guanine nucleotide exchange
      factor of Ran. At the nonpermissive temperature, importin-beta was exported from
      the nucleus of these cells, even when RanGAP1, a GTPase-activating protein for
      Ran, was co-injected. These results not only provide support for the view that
      Ran-dependent GTP hydrolysis is not required for the nuclear export of importin
      beta but also indicate that nuclear RanGTP is not essential for its export. As a
      result, we propose that importin-beta can be recycled from the nucleus alone in a
      Ran-independent manner.

PMID- 9933585
TI  - BCL-2 blocks perforin-induced nuclear translocation of granzymes concomitant with
      protection against the nuclear events of apoptosis.
AB  - Cytolytic granule-mediated target cell killing is effected in part through the
      synergistic action of the membrane-acting protein perforin and serine proteases
      such as granzymes (Gr) A and B. In this study, we examine the subcellular
      distribution of granzymes in the presence of perforin and the induction of
      apoptosis in mouse FDC-P1 myeloid and YAC-1 lymphoma cells that express the proto
      oncogene bcl2. Using confocal laser scanning microscopy to visualize and
      quantitate subcellular transport of fluoresceinated granzyme, we find that
      granzyme entry into the cytoplasm in the absence of perforin is not impaired in
      the bcl2-expressing lines. However, perforin-dependent enhancement of granzyme
      cellular uptake and, importantly, granzyme redistribution to the nucleus were
      strongly inhibited in the bcl2-expressing lines, concomitant with greatly
      increased resistance to granzyme/perforin-induced cell death. DNA fragmentation
      induced by granzyme/perforin was severely reduced in the bcl2-expressing lines,
      implying that prevention of granzyme nuclear translocation blocks the nuclear
      events of apoptosis. The kinetics of GrB nuclear uptake and induction of
      apoptosis were faster than for GrA, whereas YAC-1 cells showed greater resistance
      to granzyme nuclear uptake and apoptosis than FDC-P1 cells. In all cases,
      granzyme nuclear accumulation in the presence of perforin correlated precisely
      with ensuing apoptosis. All results supported the idea that GrA and GrB share a
      common, specific nuclear targeting pathway that contributes significantly to the
      nuclear changes of apoptosis.

PMID- 9933586
TI  - Structural basis for the differential toxicity of cholera toxin and Escherichia
      coli heat-labile enterotoxin. Construction of hybrid toxins identifies the A2
      domain as the determinant of differential toxicity.
AB  - Cholera toxin (Ctx) and E. coli heat-labile enterotoxin (Etx) are structurally
      and functionally similar AB5 toxins with over 80% sequence identity. When their
      action in polarized human epithelial (T84) cells was monitored by measuring toxin
      induced Cl- ion secretion, Ctx was found to be the more potent of the two toxins.
      Here, we examine the structural basis for this difference in toxicity by
      engineering a set of mutant and hybrid toxins and testing their activity in T84
      cells. This revealed that the differential toxicity of Ctx and Etx was (i) not
      due to differences in the A-subunit's C-terminal KDEL targeting motif (which is
      RDEL in Etx), as a KDEL to RDEL substitution had no effect on cholera toxin
      activity; (ii) not attributable to the enzymatically active A1-fragment, as
      hybrid toxins in which the A1-fragment in Ctx was substituted for that of Etx
      (and vice versa) did not alter relative toxicity; and (iii) not due to the B
      subunit, as the replacement of the B-subunit in Ctx for that of Etx caused no
      alteration in toxicity, thus excluding the possibility that the broader receptor
      specificity of EtxB is responsible for reduced activity. Remarkably, the
      difference in toxicity could be mapped to a 10-amino acid segment of the A2
      fragment that penetrates the central pore of the B-subunit pentamer. A comparison
      of the in vitro stability of two hybrid toxins, differing only in this 10-amino
      acid segment, revealed that the Ctx A2-segment conferred a greater stability to
      the interaction between the A- and B-subunits than the corresponding segment from
      Etx A2. This suggests that the reason for the relative potency of Ctx compared
      with Etx stems from the increased ability of the A2-fragment of Ctx to maintain
      holotoxin stability during uptake and transport into intestinal epithelia.

PMID- 9933587
TI  - Identification of a functional peroxisome proliferator-responsive element in the
      murine fatty acid transport protein gene.
AB  - Fatty acid transport protein (FATP), a plasma membrane protein implicated in
      controlling adipocyte transmembrane fatty acid flux, is up-regulated as a
      consequence of adipocyte differentiation and down-regulated by insulin. Based
      upon the sequence of the FATP gene upstream region (Hui, T. Y., Frohnert, B. I.,
      Smith, A. J., Schaffer, J. A., and Bernlohr, D. A. (1998) J. Biol. Chem. 273,
      27420-27429) a putative peroxisome proliferator-activated receptor response
      element (PPRE) is present from -458 to -474. To determine whether the FATP PPRE
      was functional, and responded to lipid activators, transient transfection of FATP
      luciferase reporter constructs into CV-1 and 3T3-L1 cells was carried out. In CV
      1 cells, FATP-luciferase activity was up-regulated 4- and 5.5-fold, respectively,
      by PPARalpha and PPARgamma in the presence of their respective activators in a
      PPRE-dependent mechanism. PPARdelta, however, was unable to mediate
      transcriptional activation under any condition. In 3T3-L1 cells, the PPRE
      conferred a small but significant increase in expression in preadipocytes, as
      well as a more robust up-regulation of FATP expression in adipocytes.
      Furthermore, the PPRE conferred the ability for luciferase expression to be up
      regulated by activators of both PPARgamma and retinoid X receptor alpha
      (RXRalpha) in a synergistic manner. PPARalpha and PPARdelta activators did not up
      regulate FATP expression in 3T3-L1 adipocytes, however, suggesting that these two
      subtypes do not play a significant role in differentiation-dependent activation
      in fat cells. Electromobility shift assays showed that all three PPAR subtypes
      were able to bind specifically to the PPRE as heterodimers with RXRalpha. Nuclear
      extracts from 3T3-L1 adipocytes also showed a specific gel-shift complex with the
      FATP PPRE. To correlate the expression of FATP to its physiological function,
      treatment of 3T3-L1 adipocytes with PPARgamma and RXRalpha activators resulted in
      an increased uptake of oleate. Moreover, linoleic acid, a physiological ligand,
      up-regulated FATP expression 2-fold in a PPRE-dependent manner. These results
      demonstrate that the FATP gene possesses a functional PPRE and is up-regulated by
      activators of PPARalpha and PPARgamma, thereby linking the activity of the
      protein to the expression of its gene. Moreover, these results have implications
      for the mechanism by which certain PPARgamma activators such as the antidiabetic
      thiazolidinedione drugs affect adipose lipid metabolism.

PMID- 9933588
TI  - Acute inhibition of Na/H exchanger NHE-3 by cAMP. Role of protein kinase a and
      NHE-3 phosphoserines 552 and 605.
AB  - Regulation of the renal Na/H exchanger NHE-3 by protein kinase A (PKA) is a key
      intermediate step in the hormonal regulation of acid-base and salt balance. We
      studied the role of NHE-3 phosphorylation in this process in NHE-deficient AP-1
      cells transfected with NHE-3 and in OKP cells expressing native NHE-3. A dominant
      negative PKA-regulatory subunit completely abolished the effect of cAMP on NHE-3
      activity demonstrating a role of PKA in the functional regulation of NHE-3 by
      cAMP. NHE-3 isolated from cAMP-treated cells showed lower phosphorylation by
      purified PKA in vitro suggesting that NHE-3 is a PKA substrate in vivo. Although
      changes in NHE-3 whole protein phosphorylation is difficult to detect in response
      to cAMP addition, the tryptic phosphopeptide map of in vivo phosphorylated NHE-3
      showed a complex pattern of constitutive and cAMP-induced phosphopeptides. To
      test the causal relationship between phosphorylation and activity, we mutated
      eight serines in the cytoplasmic domain to glycine or alanine. Single or multiple
      mutants harboring S552A or S605G showed no PKA activation or reduced regulation
      by PKA activation. Ser-552 and Ser-605 were phosphorylated in vivo. However,
      multiple mutations of serines other than Ser-552 or Ser-605 also reduced the
      functional PKA regulation. We conclude that regulation of NHE-3 by PKA in vivo
      involves complex mechanisms, which include phosphorylation of Ser-552 and Ser
      605.

PMID- 9933589
TI  - Truncation of macrophage-derived chemokine by CD26/ dipeptidyl-peptidase IV
      beyond its predicted cleavage site affects chemotactic activity and CC chemokine
      receptor 4 interaction.
AB  - The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) and chemokines are
      known key players in immunological processes. Surprisingly, CD26/DPP IV not only
      removed the expected Gly1-Pro2 dipeptide from the NH2 terminus of macrophage
      derived chemokine (MDC) but subsequently also the Tyr3-Gly4 dipeptide, generating
      MDC(5-69). This second cleavage after a Gly residue demonstrated that the
      substrate specificity of this protease is less restricted than anticipated. The
      unusual processing of MDC by CD26/DPP IV was confirmed on the synthetic peptides
      GPYGANMED (MDC(1-9)) and YGANMED (MDC(3-9)). Compared with intact MDC(1-69),
      CD26/DPP IV-processed MDC(5-69) had reduced chemotactic activity on lymphocytes
      and monocyte-derived dendritic cells, showed impaired mobilization of
      intracellular Ca2+ through CC chemokine receptor 4 (CCR4), and was unable to
      desensitize for MDC-induced Ca2+-responses in CCR4 transfectants. However, MDC(5
      69) remained equally chemotactic as intact MDC(1-69) on monocytes. In contrast to
      the reduced binding to lymphocytes and CCR4 transfectants, MDC(5-69) retained its
      binding properties to monocytes and its anti-HIV-1 activity. Thus, NH2-terminal
      truncation of MDC by CD26/DPP IV has profound biological consequences and may be
      an important regulatory mechanism during the migration of Th2 lymphocytes and
      dendritic cells to germinal centers and to sites of inflammation.

PMID- 9933590
TI  - Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase.
AB  - Sphingosine-1-phosphate (SPP) produced from sphingosine by sphingosine kinase has
      recently been reported to act as intracellular second messenger for a number of
      plasma membrane receptors. In the present study, we investigated whether the
      sphingosine kinase/SPP pathway is involved in cellular signaling of the Gi
      protein-coupled formyl peptide receptor in myeloid differentiated human leukemia
      (HL-60) cells. Receptor activation resulted in rapid and transient production of
      SPP by sphingosine kinase, which was abolished after pertussis toxin treatment.
      Direct activation of heterotrimeric G proteins by AlF4- also rapidly increased
      SPP formation in intact HL-60 cells. In cytosolic preparations of HL-60 cells,
      sphingosine kinase activity was stimulated by the stable GTP analog, guanosine 5'
      O-(3-thiotriphosphate). Inhibition of sphingosine kinase by DL-threo
      dihydrosphingosine and N,N-dimethylsphingosine did not affect phospholipase C
      stimulation and superoxide production but markedly inhibited receptor-stimulated
      Ca2+ mobilization and enzyme release. We conclude that the formyl peptide
      receptor stimulates through Gi-type G proteins SPP production by sphingosine
      kinase, that the enzyme is also stimulated by direct G protein activation, and
      that the sphingosine kinase/SPP pathway apparently plays an important role in
      chemoattractant signaling in myeloid differentiated HL-60 cells.

PMID- 9933591
TI  - Oligomeric structure and regulation of Candida albicans glucosamine-6-phosphate
      synthase.
AB  - Candida albicans glucosamine-6-phosphate (GlcN-6-P) synthase was purified to
      apparent homogeneity with 52% yield from recombinant yeast YRSC-65 cells
      efficiently overexpressing the GFA1 gene. The pure enzyme exhibited Km(Gln) =
      1.56 mM and Km(Fru-6-P) = 1.41 mM and catalyzed GlcN-6-P formation with kcat =
      1150 min-1. The isoelectric point of 4.6 +/- 0.05 was estimated from isoelectric
      chromatofocusing. Gel filtration, native polyacrylamide gel electrophoresis,
      subunit cross-linking, and SDS-polyacrylamide gel electrophoresis showed that the
      native enzyme was a homotetramer of 79.5-kDa subunits, with an apparent molecular
      mass of 330-340 kDa. Results of chemical modification of the enzyme by group
      specific reagents established an essential role of a cysteinyl residue at the
      glutamine-binding site and histidyl, lysyl, arginyl, and tyrosyl moieties at the
      Fru-6-P-binding site. GlcN-6-P synthase in crude extract was effectively
      inhibited by UDP-GlcNAc (IC50 = 0.67 mM). Purification of the enzyme markedly
      decreased the sensitivity to the inhibitor, but this could be restored by
      addition of another effector, glucose 6-phosphate. Binding of UDP-GlcNAc to the
      pure enzyme in the presence of Glc-6-P showed strong negative cooperativity, with
      nH = 0.54, whereas in the absence of this sugar phosphate no cooperative effect
      was observed. Pure enzyme was a substrate for cAMP-dependent protein kinase, the
      action of which led to the substantial increase of GlcN-6-P synthase activity,
      correlated with an extent of protein phosphorylation. The maximal level of
      activity was observed for the enzyme molecules containing 1. 21 +/- 0.08 mol of
      phosphate/mol of GlcN-6-P synthase. Monitoring of GlcN-6-P synthase activity and
      its sensitivity to UDP-GlcNAc during yeast --> mycelia transformation of C.
      albicans cells, under in situ conditions, revealed a marked increase of the
      former and a substantial fall of the latter.

PMID- 9933592
TI  - Polyadenylation promotes degradation of 3'-structured RNA by the Escherichia coli
      mRNA degradosome in vitro.
AB  - Polyadenylation contributes to the destabilization of bacterial mRNA. We have
      investigated the role of polyadenylation in the degradation of RNA by the
      purified Escherichia coli degradosome in vitro. RNA molecules with 3'-ends
      incorporated into a stable stem-loop structure could not readily be degraded by
      purified polynucleotide phosphorylase or by the degradosome, even though the
      degradosome contains active RhlB helicase which normally facilitates degradation
      of structured RNA. The exoribonucleolytic activity of the degradosome was due to
      polynucleotide phosphorylase, rather than the recently reported exonucleolytic
      activity exhibited by a purified fragment of RNase E (Huang, H., Liao, J., and
      Cohen, S. N. (1998) Nature 391, 99-102). Addition of a 3'-poly(A) tail stimulated
      degradation by the degradosome. As few as 5 adenosine residues were sufficient to
      achieve this stimulation, and generic sequences were equally effective. The data
      show that the degradosome requires a single-stranded "toehold" 3' to a secondary
      structure to recognize and degrade the RNA molecule efficiently; polyadenylation
      can provide this single-stranded 3'-end. Significantly, oligo(G) and oligo(U)
      tails were unable to stimulate degradation; for oligo(G), at least, this is
      probably due to the formation of a G quartet structure which makes the 3'-end
      inaccessible. The inaccessibility of 3'-oligo(U) sequences is likely to have a
      role in stabilization of RNA molecules generated by Rho-independent terminators.

PMID- 9933593
TI  - Hormone-dependent recruitment of NF-Y to the uteroglobin gene enhancer associated
      with chromatin remodeling in rabbit endometrial epithelium.
AB  - Expression of the rabbit uteroglobin gene is hormonally induced in cells of the
      endometrial epithelium during the preimplantation phase of pregnancy. Here we
      show that progesterone activation of the gene is mediated by two clusters of
      hormone responsive elements located between 2.4 and 2.7 kilobase pairs upstream
      of the transcriptional start site. Between these two clusters, genomic
      footprinting studies in the intact endometrial epithelium reveal the hormone
      inducible occupancy of several cis-acting elements. One of the protected elements
      shows sequence homology to the consensus binding site of the transcription factor
      NF-Y, which binds to the element in gel shift experiments. This uteroglobin Y box
      is essential for enhancer activity in transient transfection experiments with
      endometrial and non-endometrial cell lines, in accordance with the ubiquitous
      expression of NF-Y. To understand why binding of this ubiquitous factor to the
      uteroglobin Y box in endometrium depends on hormone induction, we examined the
      chromatin structure of the relevant gene region. In the uninduced state, the
      enhancer region appears to be organized into positioned nucleosomes. Upon hormone
      induction, this nucleosomal pattern is lost and the enhancer region becomes
      hypersensitive to nucleases, suggesting that a hormone-induced change in the
      local chromatin structure unmasks previously unaccessible binding sites for
      transcription factors. Our results emphasize the limitations of using transient
      transfection assays for the functional analysis of cis-acting elements and
      underline the need for including the native chromatin organization in this kind
      of studies.

PMID- 9933595
TI  - Multiple involvement of clusterin in chicken ovarian follicle development.
      Binding to two oocyte-specific members of the low density lipoprotein receptor
      gene family.
AB  - The interaction of the female germ cell with somatic cells during the development
      of the ovarian follicle in the chicken provides a prime system to study gene
      expression. Here, we have uncovered the involvement of clusterin, the function(s)
      of which is still poorly understood, in this complex process. As revealed by
      molecular cloning, chicken clusterin is a 428-residue protein that migrates at 70
      kDa on SDS-polyacrylamide gel electrophoresis and possesses most of the
      structural features of its mammalian successors. However, in contrast to
      mammalian clusterin, the chicken protein appears not to be cleaved
      intracellularly into a disulfide-linked heterodimer; possibly as a consequence
      thereof, it is not secreted constitutively and is absent from the circulation,
      where most of clusterin is found in mammals. In the ovary, clusterin is a major
      product of the somatic granulosa cells, in a pattern correlating with the
      developmental phases of individual follicles. In that, transcript levels are high
      not only at onset of vitellogenesis, but also in atretic follicles and in the
      postovulatory follicle sac, i.e. in situations characterized by apoptotic events.
      Yolk of growing oocytes contains a 43-kDa truncated form of clusterin that does
      not appear to be synthesized within the oocyte. Rather, we here show for the
      first time that 70-kDa clusterin interacts not only with megalin, but also with
      two chicken oocyte-specific members of the low density lipoprotein receptor
      (LDLR) gene family. These receptors, termed LDLR-related protein with eight
      ligand binding repeats (LR8) and LDLR-related protein (380 kDa), likely
      internalize granulosa cell-derived 70-kDa clusterin, which may subsequently be
      processed to the 43-kDa product. Thus, chicken clusterin could serve as a marker
      for follicular atresia and resorption, and, based on its ability to bind several
      other proteins, it may serve as carrier for the receptor-mediated endocytosis
      into oocytes of components important for embryonic development, two hitherto
      unknown functions of this intriguing protein.

PMID- 9933594
TI  - Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of
      Munc18.
AB  - Munc18a, a mammalian neuronal homologue of Saccharomyces cerevisiae Sec1p
      protein, is essential for secretion, likely as a result of its high affinity
      interaction with the target SNARE protein syntaxin 1a (where SNARE is derived
      from SNAP receptor (the soluble N-ethylmaleimide-sensitive fusion protein)).
      However, this interaction inhibits vesicle SNARE interactions with syntaxin that
      are required for secretory vesicles to achieve competency for membrane fusion. As
      such, regulation of the interaction between Munc18a and syntaxin 1a may provide
      an important mechanism controlling secretory responsiveness. Cyclin-dependent
      kinase 5 (Cdk5), a member of the Cdc2 family of cell division kinases, co
      purifies with Munc18a from rat brain, interacts directly with Munc18a in vitro,
      and utilizes Munc18a as a substrate for phosphorylation. We have now demonstrated
      that Cdk5 is capable of phosphorylating Munc18a in vitro within a preformed
      Munc18a.syntaxin 1a heterodimer complex and that this results in the disassembly
      of the complex. Using site-directed mutagenesis, the Cdk5 phosphorylation site on
      Munc18a was identified as Thr574. Stimulation of secretion from neuroendocrine
      cells produced a corresponding rapid translocation of cytosolic Cdk5 to a
      particulate fraction and an increase of Cdk5 kinase activity. Inhibition of Cdk5
      with olomoucine decreased evoked norepinephrine secretion from chromaffin cells,
      an effect not observed with the inactive analogue iso-olomoucine. The effects of
      olomoucine were independent of calcium influx as evidenced by secretory
      inhibition in permeabilized chromaffin cells and in cells under whole-cell
      voltage clamp. Furthermore, transfection and expression in chromaffin cells of a
      neural specific Cdk5 activator, p25, led to a strong increase in nicotinic
      agonist-induced secretory responses. Our data suggest a model whereby Cdk5 acts
      to regulate Munc18a interaction with syntaxin 1a and thereby modulates the level
      of vesicle SNARE interaction with syntaxin 1a and secretory responsiveness.

PMID- 9933596
TI  - The proximal tyrosines of the cytoplasmic domain of the beta chain of the type I
      interferon receptor are essential for signal transducer and activator of
      transcription (Stat) 2 activation. Evidence that two Stat2 sites are required to
      reach a threshold of interferon alpha-induced Stat2 tyrosine phosphorylation that
      allows normal formation of interferon-stimulated gene factor 3.
AB  - The precise role of the different subunits (alpha/IFNAR1 and betaL/IFNAR2) of the
      type I interferon receptor (IFN-R) in the activation of signal transducer and
      activator of transcription (Stat) 1, Stat2, and Stat3 has not yet been
      established. In this report we demonstrate that there are functionally redundant
      phosphotyrosine-dependent and -independent binding sites for Stat2 in the alpha
      and beta subunits of the type I IFN-R. Expression of a type I IFN-R containing
      only the constitutive Stat2 site or the proximal tyrosines of betaL, but not the
      docking site on the alpha chain (Tyr466 and Tyr481), supported low levels of
      Stat2 activation. However, the presence of only one intact Stat2 site did not
      lead to induction of interferon-stimulated gene factor 3 (ISGF3) or an antiviral
      state. Normal levels of Stat2 tyrosine phosphorylation, induction of ISGF3, and
      an antiviral effect always required the proximal tyrosines of betaL and at least
      one of the other Stat2 sites (Tyralpha466, 481 or betaL404-462). These data
      suggest that a threshold of Stat2 tyrosine phosphorylation is required for
      complete activation of ISGF3. Interestingly, a receptor in which all tyrosines
      were mutated to phenylalanine shows normal Stat3 phosphorylation and low levels
      of activation of Stat1.

PMID- 9933598
TI  - Dual signal peptides mediate the signal recognition particle/Sec-independent
      insertion of a thylakoid membrane polyprotein, PsbY.
AB  - The nuclear psbY gene (formerly ycf32) encodes two distinct single-spanning
      chloroplast thylakoid membrane proteins in Arabidopsis thaliana. After import
      into the chloroplast, the precursor protein is processed to a polyprotein in
      which each "mature" protein is preceded by an additional hydrophobic region; we
      show that these regions function as signal peptides that are cleaved after
      insertion into the thylakoid membrane. Inhibition of the first or second signal
      cleavage reaction by enlargement of the -1 residues leads in each case to the
      accumulation of a thylakoid-integrated intermediate containing three hydrophobic
      regions after import into chloroplasts; a double mutant is converted to a protein
      containing all four hydrophobic regions. We propose that the overall insertion
      process involves (i) insertion as a double-loop structure, (ii) two cleavages by
      the thylakoidal processing peptidase on the lumenal face of the membrane, and
      (iii) cleavage by an unknown peptidase on the stromal face on the membrane
      between the first mature protein and the second signal peptide. We also show that
      this polyprotein can insert into the thylakoid membrane in the absence of stromal
      factors, nucleoside triphosphates, or a functional Sec apparatus; this
      effectively shows for the first time that a multispanning protein can insert
      posttranslationally without the aid of signal recognition particle, SecA, or the
      membrane-bound Sec machinery.

PMID- 9933597
TI  - Hydrolysis of peptide hormones by endothelin-converting enzyme-1. A comparison
      with neprilysin.
AB  - Endothelins are peptide hormones with a potent vasoconstrictor activity that are
      also known to function as intercellular signaling molecules. The final step in
      the biosynthesis of endothelins is the proteolytic processing of precursor
      peptides by endothelin-converting enzymes (ECEs). ECE-1 is a zinc
      metalloendopeptidase related in amino acid sequence to neprilysin, a mammalian
      cell-surface peptidase involved in the metabolism of numerous biologically active
      peptides. Despite apparent structural similarities, ECE-1 and neprilysin have
      been considered to differ significantly in substrate specificity. In this study
      we have examined the activity of recombinant ECE-1 against a collection of
      biologically active peptides. ECE-1, unlike neprilysin, was found to have minimal
      activity against substrates smaller than hexapeptides, such as Leu-enkephalin.
      Larger peptides such as neurotensin, substance P, bradykinin, and the oxidized
      insulin B chain were hydrolyzed by ECE-1 as efficiently as big endothelin-1, a
      known in vivo substrate. Identification of the products of hydrolysis of six
      peptides indicates that ECE-1 has a substrate specificity similar to that of
      neprilysin, preferring to cleave substrates at the amino side of hydrophobic
      residues. The data indicate that ECE-1 possesses a surprisingly broad substrate
      specificity and is potentially involved in the metabolism of biologically active
      peptides distinct from the endothelins.

PMID- 9933599
TI  - Functional and cooperative interactions between the homeodomain PDX1, Pbx, and
      Prep1 factors on the somatostatin promoter.
AB  - Expression of the somatostatin gene in endocrine pancreatic cells is controlled
      by several regulatory cis-elements located in the promoter region. Among these,
      the adjacent UE-A and TSEI elements, located from -113 to -85 relative to the
      transcription initiation site, function in combination and act as a pancreas
      specific mini-enhancer. The TSEI element is recognized by the pancreatic
      homeodomain factor PDX1. In the present study, we show that the UE-A element
      binds a heterodimeric complex composed of a Pbx factor and the Prep1 protein,
      both belonging to the atypical three-amino acid loop extension homeodomain
      family. Recombinant Pbx1 and Prep1 proteins bind cooperatively to the UE-A site,
      whereas neither protein can bind this site alone. Transient transfection
      experiments reveal that both Pbx1 and Prep1 are required to generate a strong
      transcriptional activation from the UE-A element when this element is inserted
      close to the TATA box. In contrast, in the context of the intact somatostatin
      promoter or mini-enhancer, Pbx1 and Prep1 alone have no effect, but they produce
      a drastic activation when the pancreatic homeodomain factor PDX1 is also
      coexpressed. Thus, the activity of the somatostatin mini-enhancer is mediated by
      a cooperative interaction between the Pbx-Prep1 heterodimeric complex and the
      pancreatic factor PDX1.

PMID- 9933600
TI  - A K319N/E325Q double mutant of the lactose permease cotransports H+ with lactose.
      Implications for a proposed mechanism of H+/lactose symport.
AB  - In this study, we have examined the transport characteristics of the wild-type
      lactose permease, single mutants in which Lys-319 was changed to asparagine or
      alanine or Glu-325 was changed to glutamine or alanine, and the corresponding
      double mutant strains. The wild-type and Asn-319 mutant showed high levels of
      lactose uptake, with Km values of 0.42 and 1.30 mM and Vmax values of 102.6 and
      48.3 nmol of lactose/min/mg of protein, respectively. The Asn-319/Gln-325 strain
      had a normal Km of 0.36 mM and a moderate Vmax of 18.5 nmol of lactose/min/mg of
      protein. By comparison, the single E325Q strain had a normal Km of 0.27 mM but a
      very defective Vmax of 1.3 nmol of lactose/min/mg of protein. A similar trend was
      observed among the alanine substitutions at these positions, although the Vmax
      values were lower for the Ala-319 mutations. When comparing the Vmax values
      between the single position 325 mutants with those of the double mutants, these
      results indicate that neutral 319 mutations substantially alleviate a defect in
      Vmax caused by neutral 325 mutations. With regard to H+/lactose coupling, the
      wild-type permease is normally coupled and can transport lactose against a
      gradient. The position 325 single mutants showed no evidence of H+ transport with
      lactose or thiodigalactoside (TDG) and were unable to facilitate uphill lactose
      transport. The single Asn-319 mutant and double Asn-319/Gln-325 mutant were able
      to transport H+ upon the addition of lactose or TDG. In addition, both of these
      strains catalyzed a sugar-dependent H+ leak that inhibited cell growth in the
      presence of TDG. These two strains were also defective in uphill transport, which
      may be related to their sugar-dependent leak pathway. Based on these and other
      results in the literature, a model is presented that describes how the
      interactions among several ionizable residues within the lactose permease act in
      a concerted manner to control H+/lactose coupling. In this model, Lys-319 and Glu
      325 play a central role in governing the ability of the lactose permease to
      couple the transport of H+ and lactose.

PMID- 9933601
TI  - Biochemical investigations and mapping of the calcium-binding sites of heparinase
      I from Flavobacterium heparinum.
AB  - The heparinases from Flavobacterium heparinum are lyases that specifically cleave
      heparin-like glycosaminoglycans. Previously, amino acids located in the active
      site of heparinase I have been identified and mapped. In an effort to further
      understand the mechanism by which heparinase I cleaves its polymer substrate, we
      sought to understand the role of calcium, as a necessary cofactor, in the
      enzymatic activity of heparinase I. Specifically, we undertook a series of
      biochemical and biophysical experiments to answer the question of whether
      heparinase I binds to calcium and, if so, which regions of the protein are
      involved in calcium binding. Using the fluorescent calcium analog terbium, we
      found that heparinase I tightly bound divalent and trivalent cations.
      Furthermore, we established that this interaction was specific for ions that
      closely approximate the ionic radius of calcium. Through the use of the
      modification reagents N-ethyl-5-phenylisoxazolium-3'-sulfonate (Woodward's
      reagent K) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, we
      showed that the interaction between heparinase I and calcium was essential for
      proper functioning of the enzyme. Preincubation with either calcium alone or
      calcium in the presence of heparin was able to protect the enzyme from
      inactivation by these modifying reagents. In addition, through mapping studies of
      Woodward's reagent K-modified heparinase I, we identified two putative calcium
      binding sites, CB-1 (Glu207-Ala219) and CB-2 (Thr373-Arg384), in heparinase I
      that not only are specifically modified by Woodward's reagent K, leading to loss
      of enzymatic activity, but also conform to the calcium-coordinating consensus
      motif.

PMID- 9933602
TI  - The calcium-binding sites of heparinase I from Flavobacterium heparinum are
      essential for enzymatic activity.
AB  - In the accompanying paper (Shriver, Z., Liu, D., Hu, Y., and Sasisekharan, R.
      (1999) J. Biol. Chem. 274, 4082-4088), we have shown that calcium binds
      specifically to heparinase I and have identified two major calcium-binding sites
      (CB-1 and CB-2) that partly conform to the EF-hand calcium-binding motif. In this
      study, through systematic site-directed mutagenesis, we have confirmed the
      accompanying biochemical studies and have shown that both CB-1 and CB-2 are
      involved in calcium binding and enzymatic activity. More specifically, we
      identified critical residues (viz. Asp210, Asp212, Gly213, and Thr216 in CB-1 and
      Asn375, Tyr379, and Glu381 in CB-2) that are important for calcium binding and
      heparinase I enzymatic activity. Mutations in CB-1 resulted in a lower kcat, but
      did not change the product profile of heparinase I action on heparin; conversely,
      mutations in CB-2 not only altered the kcat for heparinase I, but also resulted
      in incomplete degradation, leading to longer saccharides. Fluorescence
      competition experiments along with heparin affinity chromatography suggested that
      mutations in CB-1 alter heparinase I activity primarily through decreasing the
      enzyme's affinity for its calcium cofactor without altering heparin binding to
      heparinase I. Compared with CB-1 mutations, mutations in CB-2 affected calcium
      binding to a lesser extent, but they had a more pronounced effect on heparinase I
      activity, suggesting a different role for CB-2 in the enzymatic action of
      heparinase I. These results, taken together with our accompanying study, led us
      to propose a model for calcium binding to heparinase I that includes both CB-1
      and CB-2 providing critical interactions, albeit via a different mechanism.
      Through binding to CB-1 and/or CB-2, we propose that calcium may play a role in
      the catalytic mechanism and/or in the exolytic processive mechanism of heparin
      like glycosaminoglycan depolymerization by heparinase I.

PMID- 9933603
TI  - Cooperation of p38 and extracellular signal-regulated kinase mitogen-activated
      protein kinase pathways during granulocyte colony-stimulating factor-induced
      hemopoietic cell proliferation.
AB  - Hemopoietic cytokines such as interleukin-3 and granulocyte colony-stimulating
      factor (G-CSF) are potent activators of hemopoietic cell growth and strongly
      induce activation of extracellular signal-regulated kinase (ERK), c-Jun-N
      terminal kinase (JNK), and p38 mitogen-activated protein (MAP) kinases. However,
      the role of these kinases is unclear. Using specific chemical inhibitors for MEK
      and p38, we demonstrate here that both ERK and p38 pathways are critically
      involved in the transduction of a proliferative signal and cooperate in G-CSF
      induced cell proliferation. We show that, like ERK and JNK activation, activation
      of p38 and its downstream substrate MAP kinase-activated protein kinase 2 by
      interleukin-3 or G-CSF requires Ras activation. We demonstrate that two distinct
      cytoplasmic regions of the G-CSF receptor are involved in activation of the p38
      pathway: a region within the 100 membrane-proximal amino acids is sufficient to
      induce low levels of p38 and MAP kinase-activated protein kinase 2 activation,
      whereas the membrane-distal phosphorylation site Tyr763 mediates strong
      activation of these kinases. The levels of p38 activation correlate closely with
      those of Ras activation by G-CSF, suggesting that the degree of Ras activation is
      a critical determinant for the extent of p38 activation by hemopoietic cytokines.

PMID- 9933604
TI  - Haemophilus ducreyi produces a novel sialyltransferase. Identification of the
      sialyltransferase gene and construction of mutants deficient in the production of
      the sialic acid-containing glycoform of the lipooligosaccharide.
AB  - Haemophilus ducreyi, the cause of the sexually transmitted disease chancroid
      produces a lipooligosaccharide (LOS) containing a terminal sialyl N
      acetyllactosamine trisaccharide. Previously, we reported the identification and
      characterization of the N-acetylneuraminic acid cytidylsynthetase gene (neuA).
      Forty-nine base pairs downstream of the synthetase gene is an open reading frame
      (ORF) encoding a protein with a predicted molecular weight of 34,646. This
      protein has weak homology to the polysialyltransferase of Escherichia coli K92.
      Downstream of this ORF is the gene encoding the H. ducreyi homologue of the
      Salmonella typhimurium rmlB gene. Mutations were constructed in the neuA gene and
      the gene encoding the second ORF by insertion of an Omega kanamycin cassette, and
      isogenic strains were constructed. LOS was isolated from each strain and
      characterized by SDS-polyacrylamide gel electrophoresis, carbohydrate, and mass
      spectrometric analysis. LOS isolated from strains containing a mutation in neuA
      or in the second ORF, designated lst, lacked the sialic acid-containing
      glycoform. Complementation studies were performed. The neuA gene and the lst gene
      were each cloned into the shuttle vector pLS88 after polymerase chain reaction
      amplification. Complementation of the mutation in the lst gene was observed, but
      we were unable to complement the neuA mutation. Since it is possible that
      transcription of the neuA gene and the lst gene were coupled, we constructed a
      nonpolar mutation in the neuA gene. In this construct, the neuA mutation was
      complemented, suggesting transcriptional coupling of the neuA gene and the lst
      gene. Sialyltransferase activity was detected by incorporation of 14C-labeled
      NeuAc from CMP-NeuAc into trichloroacetic acid-precipitable material when the lst
      gene was overexpressed in the nonpolar neuA mutant. We conclude that the lst gene
      encodes the H. ducreyi sialyltransferase. Since the lst gene product has little,
      if any, structural relationship to other sialyltransferases, this protein
      represents a new class of sialyltransferase.

PMID- 9933605
TI  - Probability analysis of variational crystallization and its application to gp120,
      the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV
      1).
AB  - The extensive glycosylation and conformational mobility of gp120, the envelope
      glycoprotein of type 1 human immunodeficiency virus (HIV-1), pose formidable
      barriers for crystallization. To surmount these difficulties, we used probability
      analysis to determine the most effective crystallization approach and derive
      equations which show that a strategy, which we term variational crystallization,
      substantially enhances the overall probability of crystallization for gp120.
      Variational crystallization focuses on protein modification as opposed to
      crystallization screening. Multiple variants of gp120 were analyzed with an
      iterative cycle involving a limited set of crystallization conditions and
      biochemical feedback on protease sensitivity, glycosylation status, and
      monoclonal antibody binding. Sources of likely conformational heterogeneity such
      as N-linked carbohydrates, flexible or mobile N and C termini, and variable
      internal loops were reduced or eliminated, and ligands such as CD4 and antigen
      binding fragments (Fabs) of monoclonal antibodies were used to restrict
      conformational mobility as well as to alter the crystallization surface. Through
      successive cycles of manipulation involving 18 different variants, we succeeded
      in growing six different types of gp120 crystals. One of these, a ternary complex
      composed of gp120, its receptor CD4, and the Fab of the human neutralizing
      monoclonal antibody 17b, diffracts to a minimum Bragg spacing of at least 2.2 A
      and is suitable for structural analysis.

PMID- 9933606
TI  - Pax-6 and Cdx-2/3 interact to activate glucagon gene expression on the G1 control
      element.
AB  - The promoter element G1, critical for alpha-cell-specific expression of the
      glucagon gene, contains two AT-rich sequences important for transcriptional
      activity. Pax-6, a paired homeodomain protein previously shown to be required for
      normal alpha-cell development and to interact with the enhancer element G3 of the
      glucagon gene, binds as a monomer to the distal AT-rich site of G1. However,
      although the paired domain of Pax-6 is sufficient for interaction with the G3
      element, the paired domain and the homeodomain are required for high affinity
      binding to G1. In addition to monomer formation, Pax-6 interacts with Cdx-2/3, a
      caudal-related homeodomain protein binding to the proximal AT-rich site, to form
      a heterodimer on G1. Both proteins are capable of directly interacting in the
      absence of DNA. In BHK-21 cells, Pax-6 activates glucagon gene transcription both
      through G3 and G1, and heterodimerization with Cdx-2/3 on G1 leads to more than
      additive transcriptional activation. In glucagon-producing cells, both G1 and G3
      are critical for basal transcription, and the Pax-6 and Cdx-2/3 binding sites are
      required for activation. We conclude that Pax-6 is not only critical for alpha
      cell development but also for glucagon gene transcription by its independent
      interaction with the two DNA control elements, G1 and G3.

PMID- 9933607
TI  - Heat-induced oligomerization of the molecular chaperone Hsp90. Inhibition by ATP
      and geldanamycin and activation by transition metal oxyanions.
AB  - It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes
      at high temperatures and displays concomitantly a novel chaperone activity
      (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol.
      Chem., 271, 2641-2645). In order to better define these oligomerization
      properties at high temperatures and to know whether they are influenced by
      modulators of Hsp90 function, heat-induced oligomerization of highly purified
      dimeric Hsp90 has been investigated over a wide range of temperature and protein
      concentrations by native polyacrylamide gel electrophoresis and size exclusion
      chromatography. Whereas below 50 degreesC, the dimeric form is maintained over a
      large range of concentrations, at the critical temperature of 50 degreesC, a
      sharp transition from dimeric to higher order oligomeric species takes place
      within minutes, in a highly ordered process, suggesting that a conformational
      change, leading to the appearance of a new oligomerization site, occurs in Hsp90
      dimer. Moreover, at and above the critical temperature, the extent of
      oligomerization increases with Hsp90 concentration. Formation of high order
      oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP
      and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors
      of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought
      to increase surface hydrophobicity of the protein, are activators. Thus,
      oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic
      interactions that are hindered by ligands and favored by transition metal
      oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by
      specific ligands that modulate its properties also suggests that this process may
      be involved in cell protection during heat shock.

PMID- 9933608
TI  - Increased high density lipoprotein (HDL), defective hepatic catabolism of ApoA-I
      and ApoA-II, and decreased ApoA-I mRNA in ob/ob mice. Possible role of leptin in
      stimulation of HDL turnover.
AB  - Abnormalities of plasma high density lipoprotein (HDL) levels commonly reflect
      altered metabolism of the major HDL apolipoproteins, apoA-I and apoA-II, but the
      regulation of apolipoprotein metabolism is poorly understood. Two mouse models of
      obesity, ob/ob and db/db, have markedly increased plasma HDL cholesterol levels.
      The purpose of this study was to evaluate mechanisms responsible for increased
      HDL in ob/ob mice and to assess potential reversibility by leptin administration.
      ob/ob mice were found to have increased HDL cholesterol (2-fold), apoA-I (1.3
      fold), and apoA-II (4-fold). ApoA-I mRNA was markedly decreased (to 25% of wild
      type) and apoA-II mRNA was unchanged, suggesting a defect in HDL catabolism. HDL
      apoprotein turnover studies using nondegradable radiolabels confirmed a decrease
      in catabolism of apoA-I and apoA-II and a 4-fold decrease in hepatic uptake in
      ob/ob mice compared with wild-type, but similar renal uptake. Low dose leptin
      treatment markedly lowered HDL cholesterol and apoA-II levels in both ob/ob mice
      and in lean wild-type mice, and it restored apoA-I mRNA to normal levels in ob/ob
      mice. These changes occurred without significant alteration in body weight.
      Moreover, ob/ob neuropeptide Y-/- mice, despite marked attenuation of diabetes
      and obesity phenotypes, showed no change in HDL cholesterol levels relative to
      ob/ob mice. Thus, increased HDL levels in ob/ob mice reflect a marked hepatic
      catabolic defect for apoA-I and apoA-II. In the case of apoA-I, this is offset by
      decreased apoA-I mRNA, resulting in apoA-II-rich HDL particles. The studies
      reveal a specific HDL particle catabolic pathway that is down-regulated in ob/ob
      mice and suggest that HDL apolipoprotein turnover may be regulated by obesity
      and/or leptin signaling.

PMID- 9933609
TI  - A short conserved motif is required for repressor domain function in the myeloid
      specific transcription factor CCAAT/enhancer-binding protein epsilon.
AB  - CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) is expressed almost
      exclusively in the myeloid lineage of the hematopoietic system and functions
      during terminal differentiation of neutrophils and macrophages, and in the
      regulation of cytokine gene expression in macrophages and T cells. We have
      undertaken a series of structure/function studies on the murine C/EBPepsilon
      polypeptide to investigate the mechanism by which C/EBPepsilon activates
      transcription. Studies with deletion mutants and fusion proteins consisting of
      C/EBPepsilon sequences joined to the Gal4 DNA-binding protein identified two
      transcriptional activation domains in C/EBPepsilon. Removal of sequences between
      the two activation domains or sequences between the second activation domain and
      the C-terminal DNA binding domain significantly increased the activity of
      C/EBPepsilon, suggesting the presence of two separate regulatory domains
      (designated RD-1epsilon and RD-2epsilon). RD-1epsilon behaved as a classic active
      repressor domain being capable of inhibiting adjacent activation domains
      irrespective of their origin and when linked to a heterologous DNA binding
      domain. Mutagenesis studies revealed a short motif in RD-1epsilon that appears to
      be a target site for protein-protein interactions and is conserved in repressor
      domains from C/EBPbeta, Sp3, c-Fos, and FosB. The juxtaposition of activation and
      repressor domains may permit C/EBPepsilon to function as a transcriptional
      activator or repressor at different stages of myeloid differentiation or as an
      inducible transcriptional activator of cytokine genes.

PMID- 9933610
TI  - Identification of a compound origin of replication at the HMR-E locus in
      Saccharomyces cerevisiae.
AB  - Eukaryotic chromosomal origins of replication are best defined in Saccharomyces
      cerevisiae. Previous analysis of yeast origins suggests that they are relatively
      simple structures comprised of three or four small DNA sequence elements
      contained within approximately 100-200-base pair regions (Gilbert, D. M. (1998)
      Curr. Opin. Genet. Dev. 8, 194-199). In contrast, the sequence elements that may
      comprise origins in multicellular eukaryotes are largely unknown. The yeast HMR-E
      region is both a chromosomal origin of replication and a silencer that represses
      transcription of adjacent genes through a position effect. The analysis presented
      here indicated that HMR-E had a novel DNA structure that was more complex than
      defined for other yeast origins, and thus revealed that there is variation in the
      structural complexity of yeast origins. In contrast to "simple" yeast origins,
      the origin at HMR-E consisted of at least three independent subregions that had
      the capacity to initiate replication. We have termed HMR-E a compound origin to
      reflect its structural complexity. Furthermore, only one origin within the
      compound origin was a silencer.

PMID- 9933611
TI  - Ser-534 in the hinge 1 region of Arabidopsis nitrate reductase is conditionally
      required for binding of 14-3-3 proteins and in vitro inhibition.
AB  - 14-3-3 proteins bind to the hinge 1 region of nitrate reductase (NR) and inhibit
      its activity. To determine which residues of NR are required for 14-3-3
      inhibitory interactions, wild-type and mutant forms of Arabidopsis NR were
      examined in the yeast two-hybrid system and in vitro inhibition assays. NR
      fragments with or without hinge 1 were introduced into yeast with one of seven
      Arabidopsis 14-3-3 isoforms (called GF14s). NR fragments (residues 1-562 or 487
      562) containing hinge 1 interacted with all GF-14s tested; an NR fragment
      (residues 1-487) lacking hinge 1 did not. GF14 binding to NR fragments was
      dependent on Ser-534, since Asp or Ala substitutions at this site blocked the
      interaction. Revertants with second site substitutions restoring interaction
      between GF14omega and the Ala- or Asp-substituted NR fragments were identified.
      One isolate had a Lys to Glu substitution at position 531, which is in hinge 1,
      and six isolates had Ile to Leu or Phe substitutions at 561 in the heme binding
      region. Double mutant forms of holo-NR (S534D plus K531E, I561F, or I561L) were
      constructed and found to be partially inhibited by protein extracts from
      Arabidopsis containing 14-3-3 proteins. Wild-type NR is phosphorylated and
      inhibited by these extracts, but S534D single mutant forms are not. These results
      show that inhibitory NR/14-3-3 interactions are dependent on Ser-534 but only in
      the context of the wild-type sequence, since substitutions at second sites render
      14-3-3 binding and in vitro NR inhibition independent of Ser-534.

PMID- 9933612
TI  - The nuclear cap-binding complex is a novel target of growth factor receptor
      coupled signal transduction.
AB  - In an attempt to further understand how nuclear events (such as gene expression,
      nuclear import/export, and cell cycle checkpoint control) might be subject to
      regulation by extracellular stimuli, we sought to identify nuclear activities
      under growth factor control. Using a sensitive photoaffinity labeling assay that
      measured [alpha-32P]GTP incorporation into nuclear proteins, we identified the 20
      kDa subunit of the nuclear cap-binding complex (CBC) as a protein whose binding
      activity is greatly enhanced by the extracellular stimulation of serum-arrested
      cells. The CBC represents a 20- and 80-kDa heterodimer (the subunits
      independently referred to as CBP20 and CBP80, respectively) that binds the 7
      methylguanosine cap on RNAs transcribed by RNA polymerase II. This binding
      facilitates precursor messenger RNA splicing and export. We have demonstrated
      that the [alpha-32P]GTP incorporation into CBP20 was correlated with an increased
      ability of the CBC to bind capped RNA and have used the [alpha-32P]GTP
      photoaffinity assay to characterize the activation of the CBC in response to
      growth factors. We show that the CBC is activated by heregulin in HeLa cells and
      by nerve growth factor in PC12 cells as well as during the G1/S phase of the cell
      cycle and when cells are stressed with UV irradiation. Additionally, we show that
      cap-dependent splicing of precursor mRNA, a functional outcome of CBC activation,
      can be catalyzed by growth factor addition to serum-arrested cells. Taken
      together, these data identify the CBC as a nuclear target for growth factor
      coupled signal transduction and suggest novel mechanisms by which growth factors
      can influence gene expression and cell growth.

PMID- 9933613
TI  - A liposomal model that mimics the cutaneous production of vitamin D3. Studies of
      the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to
      vitamin D3.
AB  - We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3
      isomerization was enhanced by about 10 times in the skin compared with that in
      organic solvents. To elucidate the mechanism by which the rate of this reaction
      is enhanced in the skin, we developed a liposomal model that mimicked the
      enhanced isomerization of preD3 to vitamin D3 that was described in human skin.
      Using this model we studied the effect of changing the polarity of preD3 as well
      as changing the chain length and the degree of saturation of liposomal
      phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found
      that a decrease in the hydrophilic interaction of the preD3 with liposomal
      phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3
      3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a
      hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which
      decreased the hydrophobic interaction of preD3 with the phospholipids, reduced
      the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little
      difference among the rates of the conversion of preD3, its 3beta-acetate, and 25
      hydroxy derivatives to their corresponding vitamin D3 compounds. We also
      determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes
      containing phosphatidylcholines with different carbon chain lengths. The rates of
      the reaction were found to be enhanced as the number of carbons (Cn) in the
      hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion,
      these results support our hypothesis that amphipathic interactions between preD3
      and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc
      conformer, the only conformer of preD3 that can convert to vitamin D3. The
      stronger these interactions were, the more preD3 was likely in its cZc
      conformation at any moment and the faster was the rate of its conversion to
      vitamin D3.

PMID- 9933614
TI  - Insertion of the N-terminal part of PsaF from Chlamydomonas reinhardtii into
      photosystem I from Synechococcus elongatus enables efficient binding of algal
      plastocyanin and cytochrome c6.
AB  - A strain of the cyanobacterium Synechococcus elongatus was generated that
      expresses a hybrid version of the photosystem I subunit PsaF consisting of the
      first 83 amino acids of PsaF from the green alga Chlamydomonas reinhardtii fused
      to the C-terminal portion of PsaF from S. elongatus. The corresponding modified
      gene was introduced into the genome of the psaF-deletion strain FK2 by
      cointegration with an antibiotic resistance gene. The transformants express a new
      PsaF subunit similar in size to PsaF from C. reinhardtii that is assembled into
      photosystem I (PSI). Hybrid PSI complexes isolated from these strains show an
      increase by 2 or 3 orders of magnitude in the rate of P700(+) reduction by C.
      reinhardtii cytochrome c6 or plastocyanin in 30% of the complexes as compared
      with wild type cyanobacterial PSI. The corresponding optimum second-order rate
      constants (k2 = 4.0 and 1.7 x 10(7) M1 s1 for cytochrome c6 and plastocyanin) are
      similar to those of PSI from C. reinhardtii. The remaining complexes are reduced
      at a slow rate similar to that observed with wild type PSI from S. elongatus and
      the algal donors. At high concentrations of C. reinhardtii cytochrome c6, a fast
      first-order kinetic component (t(1)/(2) = 4 microseconds) is revealed, indicative
      of intramolecular electron transfer within a complex between the hybrid PSI and
      cytochrome c6. This first-order phase is characteristic for P700(+) reduction by
      cytochrome c6 or plastocyanin in algae and higher plants. However, a similar fast
      phase is not detected for plastocyanin. Cross-linking studies show that, in
      contrast to PSI from wild type S. elongatus, the chimeric PsaF of PSI from the
      transformed strain cross-links to cytochrome c6 or plastocyanin with a similar
      efficiency as PsaF from C. reinhardtii PSI. Our data indicate that development of
      a eukaryotic type of reaction mechanism for binding and electron transfer between
      PSI and its electron donors required structural changes in both PSI and
      cytochrome c6 or plastocyanin.

PMID- 9933615
TI  - Role of lysine 39 of alanine racemase from Bacillus stearothermophilus that binds
      pyridoxal 5'-phosphate. Chemical rescue studies of Lys39 --> Ala mutant.
AB  - The lysine residue binding with the cofactor pyridoxal 5'-phosphate (PLP) plays
      an important role in catalysis, such as in the transaldimination and abstraction
      of alpha-hydrogen from a substrate amino acid in PLP-dependent enzymes. We
      studied the role of Lys39 of alanine racemase (EC 5.1.1.1) from Bacillus
      stearothermophilus, the PLP-binding residue of the enzyme, by replacing it site
      specifically with alanine and characterizing the resultant K39A mutant enzyme.
      The mutant enzyme turned out to be inherently inactive, but gained an activity as
      high as about 0.1% of that of the wild-type enzyme upon addition of 0.2 M
      methylamine. The amine-assisted activity of the mutant enzyme depended on the pKa
      values and molecular volumes of the alkylamines used. A strong kinetic isotope
      effect was observed when alpha-deuterated D-alanine was used as a substrate in
      the methylamine-assisted reaction, but little effect was observed using its
      antipode. In marked contrast, only L-enantiomer of alanine showed a solvent
      isotope effect in deuterium oxide in the methylamine-assisted reaction. These
      results suggest that methylamine serves as a base not only to abstract the alpha
      hydrogen from D-alanine but also to transfer a proton from water to the alpha
      position of the deprotonated (achiral) intermediate to form D-alanine. Therefore,
      the exogenous amine can be regarded as a functional group fully representing
      Lys39 of the wild-type enzyme. Lys39 of the wild-type enzyme probably acts as the
      base catalyst specific to the D-enantiomer of alanine. Another residue specific
      to the L-enantiomer in the wild-type enzyme is kept intact in the K39A mutant.

PMID- 9933616
TI  - Genomic cloning and characterization of the human eukaryotic initiation factor
      2beta promoter.
AB  - The translation initiation factor eIF2 consists of three subunits that are
      present in equal molar amounts. The genomic DNA containing the gene for eIF2beta
      and its promoter were cloned and sequenced to characterize further the mechanism
      of their regulated synthesis. Whereas Southern blot analysis indicated that a
      number of copies of the gene may exist, only one full-length intron-containing
      copy was identified. Similar to the eIF2alpha promoter, the eIF2beta promoter is
      TATA-less, CAAT-less, and GC-rich and contains an alpha-Pal binding motif.
      Mutation of the alpha-Pal binding sequence resulted in an 8-fold decrease in
      activity when assayed by the luciferase reporter gene constructs. The data
      suggest a common mechanism of transcriptional control for the two cloned subunits
      of eIF2.

PMID- 9933617
TI  - Why superoxide imposes an aromatic amino acid auxotrophy on Escherichia coli. The
      transketolase connection.
AB  - The lack of superoxide dismutase and the consequent elevation of [O2-] imposes,
      on Escherichia coli, auxotrophies for branched chain, sulfur-containing, and
      aromatic amino acids. The former two classes of auxotrophies have already been
      explained, whereas the third is explained herein. Thus O2- is shown to interfere
      with the production of erythrose-4-phosphate, which is essential for the first
      step of the aromatic biosynthetic pathway. It does so by oxidizing the 1, 2
      dihydroxyethyl thiamine pyrophosphate intermediate of transketolase and
      inactivating this enzyme.

PMID- 9933618
TI  - The heme environment in barley hemoglobin.
AB  - To elucidate the environment and ligand structure of the heme in barley
      hemoglobin (Hb), resonance Raman and electron paramagnetic resonance
      spectroscopic studies have been carried out. The heme is shown to have bis
      imidazole coordination, and neither of the histidines has imidazolate character.
      Barley Hb has a unique heme environment as judged from the Fe-CO and C-O
      stretching frequencies in the CO complex. Two Fe-CO stretching modes are observed
      with frequencies at 534 and 493 cm-1, with relative intensities that are pH
      sensitive. The 534 cm-1 conformer shows a deuterium shift, indicating that the
      iron-bound CO is hydrogen-bonded, presumably to the distal histidine. A C-O
      stretching mode at 1924 cm-1 is assigned as being associated with the 534 cm-1
      conformer. Evidence is presented that the high Fe-CO and low C-O stretching
      frequencies (534 and 1924 cm-1, respectively) arise from a short hydrogen bond
      between the distal histidine and the CO. The 493 cm-1 conformer arises from an
      open conformation of the heme pocket and becomes the dominant population under
      acidic conditions when the distal histidine moves away from the CO. Strong
      hydrogen bonding between the bound ligand and the distal histidine in the CO
      complex of barley Hb implies that a similar structure may occur in the oxy
      derivative, imparting a high stability to the bound oxygen. This stabilization is
      confirmed by the dramatic decrease in the oxygen dissociation rate compared with
      sperm whale myoglobin.

PMID- 9933619
TI  - TGF-beta3, but not TGF-beta1, protects keratinocytes against 12-O
      tetradecanoylphorbol-13-acetate-induced cell death in vitro and in vivo.
AB  - We have examined the role that individual TGF-beta isoforms, and in particular
      TGF-beta3, play in control of epidermal homeostasis. Mice with a knockout
      mutation of the TGF-beta3 gene die a few hours after birth. A full-thickness skin
      grafting approach was used to investigate the postnatal development and
      homeostatic control of the skin of these mice. Grafted skin of mice with a
      disruption of the TGF-beta3 gene developed similarly to grafts of wild type and
      TGF-beta1 knockout animals. However, a strikingly different response was observed
      after acute treatment with the tumor promoter 12-O-tetradecanoylphorbol-13
      acetate (TPA). When exposed to TPA, the grafted skin of wild type and TGF-beta1
      knockout mice underwent a hyperplastic response similar to that of normal mouse
      skin. In marked contrast, TPA treatment of TGF-beta3 knockout grafts induced
      widespread areas of keratinocyte cell death. Analysis of cultured keratinocytes
      treated with purified TGF-beta isoforms revealed that TGF-beta3 plays a direct
      and specific function in protecting keratinocytes against TPA-induced cell death.
      The protective function of TGF-beta3 on TPA-induced cell death was not because of
      general suppression of the signaling pathways triggered by this agent, as ERK1/2
      activation occurred to a similar if not greater extent in TGF-beta3-treated
      versus control keratinocytes. Instead, TGF-beta3 treatment led to a significant
      reduction in TPA-induced c-Jun N-terminal kinase activity, which was associated
      and possibly explained by specific counteracting effects of TGF-beta3 on TPA
      induced disruption of keratinocyte focal adhesions.

PMID- 9933620
TI  - Crystal structure of neuropsin, a hippocampal protease involved in kindling
      epileptogenesis.
AB  - Neuropsin is a novel serine protease, the expression of which is highly localized
      in the limbic areas of the mouse brain and which is suggested to be involved in
      kindling epileptogenesis and hippocampal plasticity. The 2.1-A resolution crystal
      structure of neuropsin provides the first three-dimensional view of one of the
      serine proteases highly expressed in the nervous system, and reveals a serine
      protease fold that exhibits chimeric features between trypsin and nerve growth
      factor-gamma (NGFgamma), a member of the kallikrein family. Neuropsin possesses
      an N-glycosylated "kallikrein loop" but forms six disulfide bonds corresponding
      to those of trypsin. The ordered kallikrein loop projects proline toward the
      active site to restrict smaller residues or proline at the P2 position of
      substrates. Loop F, which participates in forming the S3/S4 sites, is similar to
      trypsin rather than NGFgamma. The unique conformations of loops G and H form an
      S1 pocket specific for both arginine and lysine. These characteristic loop
      structures forming the substrate-binding site suggest the novel substrate
      specificity of neuropsin and give a clue to the design of its specific
      inhibitors.

PMID- 9933621
TI  - Novel insight into the copper-ligand geometry in the crystal structure of Ulva
      pertusa plastocyanin at 1.6-A resolution. Structural basis for regulation of the
      copper site by residue 88.
AB  - The crystal structure of plastocyanin from a green alga, Ulva pertusa, has been
      determined at 1.6-A resolution. At its copper site, U. pertusa plastocyanin has a
      distorted tetrahedral coordination geometry similar to other plastocyanins. In
      comparison with structures of plastocyanins reported formerly, a Cu(II)
      Sdelta(Met92) bond distance (2.69 A) is shorter by about 0.2 A and a Cu(II)
      Sgamma(Cys84) distance is longer by less than 0.1 A in U. pertusa plastocyanin.
      These subtle but significant differences are caused by the structural change at a
      His-Met loop (His87-Met92) due to an absence of a O(Asp85)-Ogamma(Ser88) hydrogen
      bond which is found in Enteromorpha prolifera plastocyanin. In addition, poplar
      and Chlamydomonas reinhardtii plastocyanins with a glutamine at residue 88 have a
      weak cation-pi interaction with Tyr83. This interaction lengthens the Cu(II)
      Sdelta(Met92) bond of poplar and C. reinhardtii plastocyanins by 0.14 and 0.20 A,
      respectively. As a result of structural differences, U. pertusa plastocyanin has
      a less distorted geometry than the other plastocyanins. Thus, the cupric geometry
      is finely tuned by the interactions between residues 85 and 88 and between
      residues 83 and 88. This result implies that the copper site is more flexible
      than reported formerly and that the rack mechanism would be preferable to the
      entatic theory. The His-Met loop may regulate the electron transfer rate within
      the complex between plastocyanin and cytochrome f.

PMID- 9933622
TI  - Expression of uroporphyrinogen decarboxylase or coproporphyrinogen oxidase
      antisense RNA in tobacco induces pathogen defense responses conferring increased
      resistance to tobacco mosaic virus.
AB  - Transgenic tobacco plants with reduced activity of either uroporphyrinogen
      decarboxylase or coproporphyrinogen oxidase, two enzymes of the tetrapyrrole
      biosynthetic pathway, are characterized by the accumulation of photosensitizing
      tetrapyrrole intermediates, antioxidative responses, and necrotic leaf lesions.
      In this study we report on cellular responses in uroporphyrinogen decarboxylase
      and coproporphyrinogen oxidase antisense plants, normally associated with
      pathogen defense. These plants accumulate the highly fluorescent coumarin
      scopolin in their leaves. They also display increased pathogenesis-related
      protein expression and higher levels of free and conjugated salicylic acid. Upon
      tobacco mosaic virus inoculation, the plants with leaf lesions and high levels of
      PR-1 mRNA expression show reduced accumulation of virus RNA relative to wild-type
      controls. This result is indicative of an increased resistance to tobacco mosaic
      virus. We conclude that porphyrinogenesis as a result of deregulated tetrapyrrole
      synthesis induces a set of defense responses that resemble the hypersensitive
      reaction observed after pathogen attack.

PMID- 9933623
TI  - Purification and lipid dependence of the recombinant hyaluronan synthases from
      Streptococcus pyogenes and Streptococcus equisimilis.
AB  - The two hyaluronan synthases (HASs) from Streptococcus pyogenes (spHAS) and
      Streptococcus equisimilis (seHAS) were expressed in Escherichia coli as
      recombinant proteins containing His6 tails. Both enzymes were expressed as major
      membrane proteins, accounting for approximately 5-8% of the total membrane
      protein. Using nickel chelate affinity chromatography, the HASs were purified to
      homogeneity from n-dodecyl beta-D-maltoside extracts. High levels of HAS activity
      could be achieved only if the purified enzymes were supplemented with either
      bovine or E. coli cardiolipin (CL), although bovine CL gave consistently greater
      activity. Mass spectroscopic analysis revealed that the fatty acid compositions
      of these two CL preparations did not overlap. The two HAS enzymes showed similar
      but distinct activation profiles with the 10 other lipids tested. For example,
      phosphatidic acid and phosphatidylethanolamine stimulated seHAS, but not spHAS.
      Phosphatidylserine stimulated both enzymes. spHAS appears to be more CL-specific
      than seHAS, although both purified enzymes still contain endogenous CL that can
      not easily be removed. Both seHAS and spHAS were inhibited by
      phosphatidylcholine, sphingomyelin, and sulfatides and were not substantially
      stimulated by cerebrosides, phosphatidylglycerol, or phosphatidylinositol. With
      both HASs, CL increased the Km for UDP-GlcUA, but decreased the Km for UDP-GlcNAc
      and gave an overall stimulation of Vmax. A kinetic characterization of the two
      membrane-bound and purified HASs is presented in the accompanying paper (Tlapak
      Simmons, V. L., Baggenstoss, B. A., Kumari, K., Heldermon, C., and Weigel, P. H.
      (1999) J. Biol. Chem. 274, 4246-4253). Both purified HASs became inactive after
      storage for approximately 5 days at 4 degreesC. Both purified enzymes also lost
      activity over 4-5 days when stored at -80 degreesC in the presence of CL, but
      reached a level of activity that then slowly decreased over a period of months.
      Although the purified enzymes stored in the absence of CL at -80 degreesC were
      much less active, the enzymes retained this same low level of activity for at
      least 5 weeks. When both spHAS and seHAS were stored without CL at -80 degreesC,
      even after 2 months, they could be stimulated by the addition of bovine CL to
      approximately 60% of the initial activity of the freshly purified enzyme.

PMID- 9933624
TI  - Kinetic characterization of the recombinant hyaluronan synthases from
      Streptococcus pyogenes and Streptococcus equisimilis.
AB  - The two hyaluronan synthases (HASs) from Streptococcus pyogenes (spHAS) and
      Streptococcus equisimilis (seHAS) were expressed in Escherichia coli as
      recombinant proteins containing His6 tails. The accompanying paper has described
      the purification and lipid dependence of both HASs, their preference for
      cardiolipin, and their stability during storage (Tlapak-Simmons, V. L.,
      Baggenstoss, B. A., Clyne, T., and Weigel, P. H. (1999) J. Biol. Chem. 274, 4239
      4245). Kinetic characterization of the enzymes in isolated membranes gave Km
      values for UDP-GlcUA of 40 +/- 4 microM for spHAS and 51 +/- 5 microM for seHAS.
      In both cases, the Vmax profiles at various concentrations of UDP-GlcNAc were
      hyperbolic, with no evidence of cooperativity. In contrast, membrane-bound spHAS,
      but not seHAS, showed sigmoidal behavior as the UDP-GlcNAc concentration was
      increased, with a Hill number of approximately 2, indicating significant
      cooperativity. The Hill number for UDP-GlcNAc utilization by seHAS was 1,
      confirming the lack of cooperativity for UDP-GlcNAc in this enzyme. The Km values
      for UDP-GlcNAc were 60 +/- 7 microM for seHAS and 149 +/- 3 microM for spHAS in
      the isolated membranes. The kinetic characteristics of the two affinity-purified
      HAS enzymes were assessed in the presence of cardiolipin after 8-9 days of
      storage at -80 degreesC without cardiolipin. With increasing storage time, the
      enzymes showed a gradual increase in their Km values for both substrates and a
      decrease in Vmax. Even in the presence of cardiolipin, the detergent-solubilized,
      purified HASs had substantially higher Km values for both substrates than the
      membrane-bound enzymes. The KUDP-GlcUA for purified spHAS and seHAS increased 2-4
      fold. The KUDP-GlcNAc for spHAS and seHAS increased 4- and 5-fold, respectively.
      Despite the higher Km values, the Vmax values for the purified HASs were only
      approximately 50% lower than those for the membrane-bound enzymes. Significantly,
      purified spHAS displayed the same cooperative interaction with UDP-GlcNAc (nH
      approximately 2), whereas purified seHAS showed no cooperativity.

PMID- 9933625
TI  - Identification and functional expression of the plasma membrane calcium ATPase
      gene family from Caenorhabditis elegans.
AB  - Calcium-pumping ATPases are an essential component of the intracellular calcium
      homeostasis system and have been characterized in a large variety of species and
      cell types. In mammalian genomes, these proteins are encoded by gene families
      whose individual members feature complex tissue-specific expression and
      alternative splicing. In the search for a less complex system that is more
      amenable to genetic manipulation, we have identified a family of three genes (mca
      1, mca-2, and mca-3) encoding putative calcium ATPases in the Caenorhabditis
      elegans Genome Project data and completed their transcript structure. In this
      work, we report the cloning and functional expression of the mca-1 gene, which
      encodes a calcium-stimulated ATPase whose features resemble those of the plasma
      membrane calcium adenosine triphosphatase family of mammalian cells and appears
      to be regulated by a multipartite promoter.

PMID- 9933626
TI  - Actin stabilization by jasplakinolide enhances apoptosis induced by cytokine
      deprivation.
AB  - Participation of the actin cytoskeleton in the transduction of proliferative
      signals has been established through the use of compounds that disrupt the
      cytoskeleton. To address the possibility that actin also participates in the
      transduction of an apoptotic signal, we have studied the response of the murine
      interleukin 2 (IL-2)-dependent T cell line CTLL-20 to treatment with the actin
      binding compound jasplakinolide upon IL-2 deprivation. Like phalloidin,
      jasplakinolide stabilizes F-actin and promotes actin polymerization. Treatment of
      CTLL-20 cells with jasplakinolide, in the presence or absence of recombinant
      human IL-2, altered actin morphology as assessed by confocal fluorescence
      microscopy. Jasplakinolide was not toxic to CTLL-20 cells, nor was apoptosis
      induced in the presence of exogenous recombinant human IL-2. However, actin
      stabilization at the time of IL-2 deprivation enhanced apoptosis by changing the
      time at which CTLL-20 cells committed to the apoptotic pathway. This effect of
      jasplakinolide correlated with its ability to stabilize polymerized actin, as
      treatment with a synthetic analog of jasplakinolide with a greatly reduced
      ability to bind actin, jasplakinolide B, did not enhance apoptosis. The
      enhancement occurred upstream of the induction of caspase-3-like activity and
      could be inhibited by the overexpression of the anti-apoptotic protein Bcl-xL.
      These data suggest that the actin cytoskeleton plays an active role in modulating
      lymphocyte apoptosis induced by cytokine deprivation.

PMID- 9933627
TI  - The FKBP12-rapamycin-binding domain is required for FKBP12-rapamycin-associated
      protein kinase activity and G1 progression.
AB  - The immunosuppressant rapamycin, in complex with its cellular receptor FKBP12,
      targets the cellular protein FKBP12-rapamycin-associated protein/mammalian target
      of rapamycin/rapamycin and FKBP12 target 1 (FRAP/mTOR/RAFT1) and inhibits/delays
      G1 cell cycle progression in mammalian cells. As a member of the novel
      phosphatidylinositol kinase-related kinase family, FRAP's kinase activity is
      essential for its signaling function. The FKBP12-rapamycin binding (FRB) domain
      in FRAP is also speculated to play an important role in FRAP function and
      signaling. However, the biochemical and physiological functions of FRB, as well
      as the mechanism for rapamycin inhibition, have been unclear. The present study
      focuses on investigation of FRB's role and the functional relationship between
      FRB domain and kinase domain in FRAP. Microinjection of purified FRB protein into
      human osteosarcoma MG63 cells results in a drastic blockage of the G1 to S cell
      cycle progression; such a dominant negative effect is reversed by a point
      mutation (Trp2027 --> Phe). The same mutation also abolishes kinase activity of
      FRAP without affecting ATP binding, and truncation studies suggest that upstream
      sequences including FRB are required for kinase activity in vitro. Given these
      data, we propose a model for FRAP function, in which the FRB domain is required
      for activation of the kinase domain, possibly through the interaction with an
      upstream activator. In addition, our observations provide direct evidence linking
      FRAP function to G1 cell cycle progression.

PMID- 9933628
TI  - Cloning and expression of a potato cDNA encoding hydroxycinnamoyl-CoA:tyramine N
      (hydroxycinnamoyl)transferase.
AB  - Hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110)
      catalyzes the transfer of hydroxycinnamic acids from the respective CoA esters to
      tyramine and other amines in the formation of N-(hydroxycinnamoyl)amines.
      Expression of THT is induced by Phytophthora infestans, the causative agent of
      late blight disease in potato. The amino acid sequences of nine endopeptidase
      LysC-liberated peptides from purified potato THT were determined. Using
      degenerate primers, a THT-specific fragment was obtained by reverse transcription
      polymerase chain reaction, and THT cDNA clones were isolated from a library
      constructed from RNA of elicitor-treated potato cells. The open reading frame
      encoding a protein of 248 amino acids was expressed in Escherichia coli.
      Recombinant THT exhibited a broad substrate specificity, similar to that of
      native potato THT, accepting cinnamoyl-, 4-coumaroyl-, caffeoyl-, feruloyl- and
      sinapoyl-CoA as acyl donors and tyramine, octopamine, and noradrenalin as
      acceptors tested. Elicitor-induced THT transcript accumulation in cultured potato
      cells peaked 5 h after initiation of treatment, whereas enzyme activity was
      highest from 5 to 30 h after elicitation. In soil-grown potato plants, THT mRNA
      was most abundant in roots. Genomic Southern analyses indicate that, in potato,
      THT is encoded by a multigene family.

PMID- 9933629
TI  - Export of recombinant Mycobacterium tuberculosis superoxide dismutase is
      dependent upon both information in the protein and mycobacterial export
      machinery. A model for studying export of leaderless proteins by pathogenic
      mycobacteria.
AB  - We have investigated the expression and extracellular release of enzymatically
      active superoxide dismutase, one of the 10 major extracellular proteins of
      Mycobacterium tuberculosis, both in its native host and in the heterologous host
      Mycobacterium smegmatis. We found that the M. tuberculosis superoxide dismutase
      gene, encoding a leaderless polypeptide of Mr approximately 23,000 representing
      one of the four identical subunits of the enzyme, is expressed constitutively
      under normal growth conditions and at a 5-fold increased level under conditions
      of hydrogen peroxide stress. The highly pathogenic mycobacterium M. tuberculosis
      expresses 93-fold more superoxide dismutase than the nonpathogenic mycobacterium
      M. smegmatis, and it exports a much higher proportion of expressed enzyme (76
      versus 21%); taking both expression and export into consideration, M.
      tuberculosis exports approximately 350-fold more enzyme than M. smegmatis. In M.
      smegmatis, recombinant M. tuberculosis superoxide dismutase is expressed at 8.4
      times the level of the endogenous enzyme and the proportion exported (66%)
      approaches that in the homologous host; hence M. smegmatis exports up to 26-fold
      more of the recombinant than endogenous enzyme. Interestingly, subunits of the M.
      tuberculosis and M. smegmatis enzymes readily and stoichiometrically exchange
      with each other, forming five different complexes of four subunits, both when the
      enzymes are expressed in the recombinant host and when the purified enzymes are
      incubated together; however, each subunit retains its characteristic metal ion,
      iron for M. tuberculosis and manganese for M. smegmatis. Compared with the cell
      associated enzyme, the supernatant enzyme of recombinant M. smegmatis is enriched
      for M. tuberculosis enzyme subunits, consistent with preferential export of the
      M. tuberculosis enzyme. Recombinant M. tuberculosis superoxide dismutase
      transcomplements a superoxide dismutase-deficient Escherichia coli, resulting in
      a reduction of sensitivity of the strain to oxidative stress, but the enzyme is
      not exported from this nonmycobacterial host. Our findings indicate that the
      information for export of the M. tuberculosis superoxide dismutase is contained
      within the protein but that export additionally requires export machinery
      specific to mycobacteria.

PMID- 9933630
TI  - Reciprocal antagonism coordinates C-type natriuretic peptide and mitogen
      signaling pathways in fibroblasts.
AB  - The fibroblast, a cell central to effective wound remodeling, not only contains
      various growth factor receptors but also high activities of a guanylyl cyclase
      receptor (GC-B). Here we demonstrate that marked elevations of cyclic GMP induced
      by C-type natriuretic peptide (CNP), the ligand of GC-B, blocks activation of the
      mitogen-activated protein kinase cascade in fibroblasts. We also show that
      platelet-derived growth factor, fibroblast growth factor, serum, or Na3VO4
      rapidly (within 5 min) and extensively (up to 85% inhibition) disrupt CNP
      dependent elevations of cyclic GMP. In addition, the mitogens also lower cyclic
      GMP concentrations (50% decrease) in cells not treated with CNP. Cytoplasmic
      forms of guanylyl cyclase, in contrast to the CNP-stimulated pathway, are not
      antagonized by the various mitogens. The effects of the mitogens on cellular
      cyclic GMP are fully explained by a direct and stable inactivation of GC-B.
      Homogenates obtained from fibroblasts treated with or without the various
      mitogens contain equivalent amounts of GC-B protein, but both ligand-dependent
      and ligand-independent activity are markedly (up to 90% inhibition of CNP
      dependent activity) decreased after mitogen addition. The stable inactivation is
      correlated with the dephosphorylation of phosphoserine and phosphothreonine
      residues of the cyclase receptor. These results not only establish a specific and
      reciprocal antagonistic relationship between mitogen-activated and GC-B-regulated
      signaling pathways in the fibroblast but also suggest that one of the earliest
      events following mitogen activation of a fibroblast is an interruption of cyclic
      GMP production from this receptor.

PMID- 9933631
TI  - Activation of Sp1 and its functional co-operation with serum amyloid A-activating
      sequence binding factor in synoviocyte cells trigger synergistic action of
      interleukin-1 and interleukin-6 in serum amyloid A gene expression.
AB  - The serum amyloid A (SAA) protein has been implicated in the progression and
      pathogenesis of rheumatoid arthritis through induction of collagenase activity in
      synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is
      synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are
      present at significantly high level in the synovial fluid of arthritis patients.
      These cytokines induced phenotypic changes in synovial cells, promoting
      protrusion and increased cellular contact. Induction of SAA under this condition
      is mediated by promoter elements located between -254 and -226, which contains
      binding sites for transcription factors Sp1 and SAA activating sequence binding
      factor (SAF). Mutation of these sequences abolishes SAA promoter response to IL-1
      and IL-6. The role of Sp1 in SAA induction was demonstrated by increased DNA
      binding activity, phosphorylation, and increased protein content of Sp1 during
      cytokine treatment. Sp1 interacts with the SAA promoter in association with SAF
      as an SAF. Sp1 heteromeric complex. Furthermore, using a phosphatase inhibitor,
      we demonstrated increased transactivation potential of both Sp1 and SAF as a
      consequence of a phosphorylation event. These results provide first evidence for
      cytokine-mediated activation of Sp1 in synovial fibroblast cells and its
      participation in regulating SAA expression by acting in conjunction with SAF.

PMID- 9933632
TI  - NF-kappaB activation is a critical regulator of human granulocyte apoptosis in
      vitro.
AB  - During beneficial inflammation, potentially tissue-damaging granulocytes undergo
      apoptosis before being cleared by phagocytes in a non-phlogistic manner. Here we
      show that the rate of constitutive apoptosis in human neutrophils and eosinophils
      is greatly accelerated in both a rapid and concentration-dependent manner by the
      fungal metabolite gliotoxin, but not by its inactive analog methylthiogliotoxin.
      This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk,
      correlated with the inhibition of nuclear factor-kappa B (NF-kappaB), and was
      mimicked by a cell permeable inhibitory peptide of NF-kappaB, SN-50; other NF
      kappaB inhibitors, curcumin and pyrrolidine dithiocarbamate; and the proteasome
      inhibitor, MG-132. Gliotoxin also augmented dramatically the early (2-6 h) pro
      apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) in neutrophils and
      unmasked the ability of TNF-alpha to induce eosinophil apoptosis. In neutrophils,
      TNF-alpha caused a gliotoxin-inhibitable activation of an inducible form of NF
      kappaB, a response that may underlie the ability of TNF-alpha to delay apoptosis
      at later times (12-24 h) and limit its early killing effect. Furthermore,
      cycloheximide displayed a similar capacity to enhance TNF-alpha induced
      neutrophil apoptosis even at time points when cycloheximide alone had no pro
      apoptotic effect, suggesting that NF-kappaB may regulate the production of
      protein(s) which protect neutrophils from the cytotoxic effects of TNF-alpha.
      These data shed light on the biochemical and molecular mechanisms regulating
      human granulocyte apoptosis and, in particular, indicate that the transcription
      factor NF-kappaB plays a crucial role in regulating the physiological cell death
      pathway in granulocytes.

PMID- 9933634
TI  - Regulation of RNA polymerase I transcription in response to F9 embryonal
      carcinoma stem cell differentiation.
AB  - Dramatic changes in the patterns of transcription are a common feature of early
      development. We have used F9 embryonal carcinoma cells as a model system to study
      gene regulation during an early stage of murine embryogenesis. We find that
      transcription by RNA polymerase I decreases when F9 cells differentiate into
      parietal endoderm. The reduced rate of transcription is associated with a down
      regulation of several components of the class I transcription apparatus. The most
      substantial change involves the essential factor SL1, which is a multisubunit
      complex that contains the TATA-binding protein and three TATA-binding protein
      associated factors (TAFs). The abundance of two of these TAFs, TAFI48 and TAFI95,
      decreases during F9 cell differentiation. Developmental regulation of a specific
      class of genes may therefore be achieved through changes in the availability of
      TAFs.

PMID- 9933633
TI  - Different mitogen-activated protein kinase signaling pathways cooperate to
      regulate tumor necrosis factor alpha gene expression in T lymphocytes.
AB  - Tumor necrosis factor a (TNF-alpha) is a potent proinflammatory cytokine and
      plays a crucial role in early events of inflammation. TNF-alpha is primarily
      produced by monocytes and T lymphocytes. In particular, T-cell-derived TNF-alpha
      plays a critical role in autoimmune inflammation and superantigen-induced septic
      shock. However, little is known about the intracellular signaling pathways that
      regulate TNF expression in T cells. Here we show that extracellular signal
      regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38-mitogen-activated
      protein kinase (MAPK) pathways control the transcription and synthesis of TNF
      alpha in A3.01 T cells that produce the cytokine upon T cell activation by
      costimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin.
      Selective activation of each of the distinct MAPK pathways by expression of
      constitutively active kinases is sufficient for TNF-alpha promoter induction.
      Furthermore, blockage of all three pathways almost abolishes TPA/ionomycin
      induced transcriptional activation of the TNF-alpha promoter. Selective
      inhibition of one or more MAPK pathways impairs TNF-alpha induction by
      TPA/ionomycin, indicating a cooperation between these signal transduction
      pathways. Our approach revealed that the MAPK kinase 6 (MKK6)/p38 pathway is
      involved in both transcriptional and posttranscriptional regulation of TNF
      expression. Moreover, analysis of the progressive 5' deletion mutants of the TNF
      alpha promoter indicates that distinct promoter regions are targeted by either
      ERK-, JNK-, or p38-activating pathways. Thus, unlike what has been reported for
      other TNF-alpha-producing cells, all three MAPK pathways are critical and
      cooperate to regulate transcription of the TNF-alpha gene in T lymphocytes,
      suggesting a T-cell-specific regulation of the cytokine.

PMID- 9933635
TI  - Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during
      apoptosis.
AB  - Previous studies have demonstrated that topoisomerase I is cleaved late during
      apoptosis, but have not identified the proteases responsible or examined the
      functional consequences of this cleavage. Here, we have shown that treatment of
      purified topoisomerase I with caspase-3 resulted in cleavage at DDVD146 downward
      arrowY and EEED170 downward arrowG, whereas treatment with caspase-6 resulted in
      cleavage at PEDD123 downward arrowG and EEED170 downward arrowG. After treatment
      of Jurkat T lymphocytic leukemia cells with anti-Fas antibody or A549 lung cancer
      cells with topotecan, etoposide, or paclitaxel, the topoisomerase I fragment
      comigrated with the product that resulted from caspase-3 cleavage at DDVD146
      downward arrowY. In contrast, two discrete topoisomerase I fragments that
      appeared to result from cleavage at DDVD146 downward arrowY and EEED170 downward
      arrowG were observed after treatment of MDA-MB-468 breast cancer cells with
      paclitaxel. Topoisomerase I cleavage did not occur in apoptotic MCF-7 cells,
      which lack caspase-3. Cell fractionation and band depletion studies with the
      topoisomerase I poison topotecan revealed that the topoisomerase I fragment
      remains in proximity to the chromatin and retains the ability to bind to and
      cleave DNA. These observations indicate that topoisomerase I is a substrate of
      caspase-3 and possibly caspase-6, but is cleaved at sequences that differ from
      those ordinarily preferred by these enzymes, thereby providing a potential
      explanation why topoisomerase I cleavage lags behind that of classical caspase
      substrates such as poly(ADP-ribose) polymerase and lamin B1.

PMID- 9933636
TI  - Stress-activated protein kinase-2/p38 and a rapamycin-sensitive pathway are
      required for C2C12 myogenesis.
AB  - The differentiation of C2C12 myoblasts to myotubes was found to be accompanied by
      a strong activation of p70 S6 kinase and the mitogen-activated protein kinase
      (MAPK) family member SAPK2/p38, without significant activation of p42 MAPK and
      only slight activation of SAPK1/JNK and protein kinase Balpha. Consistent with
      these findings, SB 203580 (a specific inhibitor of SAPK2/p38) or rapamycin (which
      blocks the activation of p70 S6 kinase) prevented the formation of multinucleated
      myotubes, as well as the expression of muscle-specific proteins that included
      SAPK3 (another MAPK family member). PD 098059 (which prevents the activation of
      p42 MAPK) had no effect on myotube formation. Surprisingly, the slow activation
      of p70 S6 kinase during differentiation was not only prevented by rapamycin but
      also by SB 203580, and the activation of MAPKAP kinase-2 (an in vivo substrate of
      SAPK2/p38) was not only prevented by SB 203580 but also by rapamycin. In
      contrast, the acute activation of p70 S6 kinase in C2C12 myoblasts induced by
      phorbol esters was unaffected by SB 203580 and the acute activation of MAPKAP
      kinase-2 induced by anisomycin was unaffected by rapamycin. These results show
      for the first time that SAPK2/p38 plays an essential role in C2C12 cell
      differentiation.

PMID- 9933637
TI  - Sustained activation of the mitogen-activated protein kinase pathway. A mechanism
      underlying receptor tyrosine kinase specificity for matrix metalloproteinase-9
      induction and cell migration.
AB  - Activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated
      protein kinase (MAPK) pathway is required for ligand-dependent regulation of
      numerous cellular functions by receptor tyrosine kinases. We have shown
      previously that although many receptor tyrosine kinase ligands are mitogens for
      keratinocytes, cell migration and induction of the 92-kilodalton
      gelatinase/matrix metalloproteinase (MMP)-9 are selectively regulated by the
      epidermal growth factor and scatter factor/hepatocyte growth factor receptors. In
      this report we present evidence of an underlying mechanism to account for these
      observed differences in receptor tyrosine kinase-mediated response. Ligands that
      are mitogenic, but do not induce MMP-9 or colony dispersion, transiently activate
      the p42/p44 ERK/MAP kinases. In contrast, ligands that stimulate MMP-9 induction
      and colony dispersion induced sustained activation of these kinases. The
      functional significance of sustained MAPK activation was demonstrated by
      inhibition of the MAP kinase kinase MEK1. Disruption of the prolonged signal by
      addition of the MEK1 inhibitor PD 98059 up to 4 h after growth factor stimulation
      substantially impaired ligand-dependent colony dispersion and MMP-9 induction.
      These findings support the conclusion that duration of MAPK activation is an
      important determinant for certain growth factor-mediated functions in
      keratinocytes.

PMID- 9933638
TI  - Proliferating cell nuclear antigen facilitates excision in long-patch base
      excision repair.
AB  - There are two distinct pathways for the removal of modified DNA bases through
      base excision repair (BER) in vertebrates. Following 5' incision by AP
      endonuclease, the pathways diverge as two different excision mechanisms are
      possible. In short-patch repair, DNA polymerase beta accounts for both excision
      activity and single nucleotide repair synthesis. In long-patch repair, the damage
      containing strand is excised by the structure-specific endonuclease FEN-1 and
      approximately 2-8 nucleotides are incorporated by proliferating cell nuclear
      antigen (PCNA)-dependent synthesis. PCNA is an accessory factor of DNA
      polymerases delta and epsilon that is required for DNA replication and repair.
      PCNA binds to FEN-1 and stimulates its nuclease activity, but the physiological
      significance of this interaction is unknown. The importance of the PCNA-FEN-1
      interaction in BER was investigated. In a reconstituted BER assay system
      containing FEN-1, omission of PCNA caused the accumulation of pre-excision
      reaction intermediates which could be converted to completely repaired product by
      addition of PCNA. When dNTPs were omitted from the reaction to suppress repair
      synthesis, PCNA was required for the formation of excised reaction intermediates.
      In contrast, a PCNA mutant that could not bind to FEN-1 was unable to stimulate
      excision. To further study this effect, a mutant of FEN-1 was identified that
      retained full nuclease activity but was specifically defective in binding to
      PCNA. The mutant FEN-1 exhibited one-tenth the specific activity of wild type FEN
      1 in the reconstituted BER assay, and this repair defect was due to a kinetic
      block at the excision step as evidenced by the accumulation of pre-excision
      intermediates when dNTPs were omitted. These results indicate that PCNA
      facilitates excision during long-patch BER through its interaction with FEN-1.

PMID- 9933639
TI  - Biosynthesis of flavocytochrome b558 . gp91(phox) is synthesized as a 65-kDa
      precursor (p65) in the endoplasmic reticulum.
AB  - The redox center of the phagocyte NADPH oxidase is flavocytochrome b558, a
      transmembrane protein with two subunits, gp91(phox) and p22(phox). In this study
      we investigated the identity, subcellular localization, and maturation of a
      putative 65-kDa gp91(phox) precursor (p65). Expressing the gp91(phox) cDNA in an
      in vitro transcription and translation system, we found that synthesis of p65
      required endoplasmic reticulum (ER) microsomes. Sucrose density gradient
      centrifugation of postnuclear supernatants obtained from a PLB-985 derived cell
      line with a constitutively expressed gp91(phox) transgene demonstrated that p65
      co-sedimented with the ER marker protein calreticulin and myeloperoxidase
      precursors. Unexpectedly, the majority of p22(phox) was found in subcellular
      compartments containing the mature 91-kDa form of gp91(phox) and not with p65,
      suggesting that heterodimer formation may occur in a post-ER compartment. The
      heme synthesis inhibitor, succinyl acetone, reduced the abundance of mature
      gp91(phox) and p22(phox) but had little or no impact on p65. These studies
      demonstrate (a) gp91(phox) is synthesized as a glycosylated 65-kDa precursor in
      the ER, (b) heterodimer formation is not a co-translational process, and (c) heme
      insertion is a determinant in the formation of a stable heterodimer but does not
      appear to affect the stability of p65.

PMID- 9933640
TI  - GTP-bound human MxA protein interacts with the nucleocapsids of Thogoto virus
      (Orthomyxoviridae).
AB  - Human MxA protein is an interferon-induced member of the dynamin superfamily of
      large GTPases. MxA inhibits the multiplication of several RNA viruses, including
      Thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks.
      Previous studies have indicated that GTP binding is required for antiviral
      activity, but the mechanism of action is still unknown. Here, we have used an in
      vitro cosedimentation assay to demonstrate, for the first time, a GTP-dependent
      interaction between MxA GTPase and a viral target structure. The assay is based
      on highly active MxA GTPase as effector molecules, Thogoto virus nucleocapsids as
      viral targets, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) as a
      stabilizing factor. We show that MxA tightly interacts with viral nucleocapsids
      by binding to the nucleoprotein component. This interaction requires the presence
      of GTPgammaS and is mediated by domains in the carboxyl-terminal moiety of MxA.
      We propose that GTP-bound MxA adopts an antivirally active conformation that
      allows interaction with viral nucleocapsids, thereby impairing their normal
      function.

PMID- 9933641
TI  - Molecular cloning, genomic organization, and functional expression of Na+/H+
      exchanger isoform 5 (NHE5) from human brain.
AB  - To isolate a cDNA encoding Na+/H+ exchanger isoform 5 (NHE5), we screened a human
      spleen library using exon sequences of the NHE5 gene. Clones spanning 2.9
      kilobase pairs were isolated; however, they contained several introns and were
      missing coding sequences at both the 5' and 3' ends. The missing 5' sequences
      were obtained by 5'-rapid amplification of cDNA ends and by analysis of an NHE5
      genomic clone, and the missing 3' sequences were obtained by 3'-rapid
      amplification of cDNA ends. Polymerase chain reaction amplification of brain cDNA
      yielded products in which each of the introns had been correctly excised, whereas
      the introns were retained in products from spleen and testis, suggesting that the
      NHE5 transcripts expressed in these organs do not encode a functional
      transporter. The intron/exon organization of the NHE5 gene was analyzed and found
      to be very similar to that of the NHE3 gene. The NHE5 cDNA, which encodes an 896
      amino acid protein that is most closely related to NHE3, was expressed in Na+/H+
      exchanger-deficient fibroblasts and shown to mediate Na+/H+ exchange activity.
      Northern blot analysis demonstrated that the mRNA encoding NHE5 is expressed in
      multiple regions of the brain, including hippocampus, consistent with the
      possibility that it regulates intracellular pH in hippocampal and other neurons.

PMID- 9933642
TI  - Molecular cloning and functional expression of a rat Na+/H+ exchanger (NHE5)
      highly expressed in brain.
AB  - We report here the cloning, primary structure, heterologous expression, tissue
      distribution, and localization of a cDNA encoding rat NHE5, a fifth member of the
      mammalian plasma membrane Na+/H+ exchanger (NHE) gene family. The full-length
      open reading frame as well as 34 nucleotides of 5'-untranslated and 1443
      nucleotides of 3'-untranslated sequences were obtained using a polymerase chain
      reaction strategy involving reverse transcription-polymerase chain reaction and
      5'/3'-rapid amplification of cDNA ends. The NHE5 cDNA encodes a protein of 898
      amino acids with a calculated Mr of 99,044 and is predicted to contain 11-13
      transmembrane domains. An amino acid comparison of the coding region of rat NHE5
      reveals 95% identity with human NHE5. Northern hybridization analysis showed that
      high level expression of NHE5 mRNA is restricted to brain. Transfection of the
      coding region of rat NHE5 into NHE-deficient PS120 cells resulted in Na+/H+
      exchange activity that was relatively insensitive to the amiloride analogue, 5-(N
      ethyl-N-isopropyl) amiloride, with a half-maximal inhibitory concentration (IC50)
      of 1. 53 +/- 0.25 microM. In situ hybridization of rat brain sections revealed
      significant NHE5 mRNA levels in the dentate gyrus with lower levels observed in
      the hippocampus and cerebral cortex. These results suggest a specialized role for
      this fifth NHE isoform in neuronal tissues.

PMID- 9933643
TI  - Cargo can modulate COPII vesicle formation from the endoplasmic reticulum.
AB  - The COPII coat complex found on endoplasmic reticulum (ER)-derived vesicles plays
      a critical role in cargo selection. We now address the potential role of
      biosynthetic cargo in modulating COPII coat assembly and vesicle budding. The ER
      accumulation of vesicular stomatitis glycoprotein (VSV-G), a transmembrane
      protein, or the soluble PiZ variant of alpha1-antitrypsin, reduced levels of
      general COPII vesicle formation in vivo. Consistent with this result, conditions
      that prevent the export of VSV-G from the ER led to a significant inhibition of
      general COPII vesicle budding from ER microsomes and the export of an endogenous
      recycling protein p58 in vitro. In contrast, synchronized export of VSV-G
      stimulated COPII vesicle budding both in vivo and in vitro. Under conditions
      where VSV-G is retained in the ER, we find that it can to be recovered in pre
      budding complexes containing COPII components. These results suggest that the
      export of biosynthetic cargo is integrated with ER functions involved in protein
      folding and oligomerization. The ability of biosynthetic cargo to prevent or
      enhance ER export suggests that interactions of cargo with the COPII machinery
      contribute to the formation of vesicles budding from the ER.

PMID- 9933644
TI  - The transcription factor EGR-1 suppresses transformation of human fibrosarcoma
      HT1080 cells by coordinated induction of transforming growth factor-beta1,
      fibronectin, and plasminogen activator inhibitor-1.
AB  - Re-expression of EGR-1 in fibrosarcoma HT1080 suppresses transformation including
      tumorigenicity (Huang, R.-P., Liu, C., Fan, Y., Mercola, D., and Adamson, E.
      (1995) Cancer Res. 55, 5054-5062) owing in part to up-regulation of the
      transforming growth factor (TGF)-beta1 promoter by EGR-1 which suppresses growth
      by an autocrine mechanism (Liu, C., Adamson, E., and Mercola, D. (1996) Proc.
      Natl. Acad. Sci. U. S. A. 93, 11831-11836). Here we show that enhanced cell
      attachment contributes to the suppression via increased secretion of fibronectin
      (FN) and also of plasminogen activator inhibitor-1 (PAI-1). The secretion of FN
      and PAI-1 is strongly correlated with EGR-1 expression (RPEARSON = 0.971 and 0.
      985, respectively). Addition of authentic TGF-beta1 to parental cells greatly
      stimulated secretion of PAI-1 but not FN, whereas addition of TGF-beta antibody
      or lipofection with specific antisense TGF-beta1 oligonucleotides to EGR-1
      regulated cells completely inhibits the secretion of PAI-1 but not FN. However,
      in gel mobility shift assays pure EGR-1 or nuclear extracts of EGR-1-regulated
      cells specifically bind to two GC-rich elements of the human FN promoter at
      positions -75/-52 and -4/+18, indicating that the increased secretion of FN is
      likely due to direct up-regulation by EGR-1. Moreover, adhesion was greatly
      enhanced in EGR-1-regulated cells and was reversed by treatment with Arg-Gly-Asp
      (RGD) or PAI-1 antibody indicating that the secreted proteins are functional. We
      conclude that EGR-1 regulates the coordinated expression of gene products
      important for cell attachment ("oikis" factor) and normal growth control.

PMID- 9933645
TI  - Role of post-transcriptional modifications of primer tRNALys,3 in the fidelity
      and efficacy of plus strand DNA transfer during HIV-1 reverse transcription.
AB  - During HIV reverse transcription, (+) strand DNA synthesis is primed by an RNase
      H-resistant sequence, the polypurine tract, and continues as far as a 18-nt
      double-stranded RNA region corresponding to the 3' end of tRNALys,3 hybridized to
      the viral primer binding site (PBS). Before (+) strand DNA transfer, reverse
      transcriptase (RT) needs to unwind the double-stranded tRNA-PBS RNA in order to
      reverse-transcribe the 3' end of primer tRNALys,3. Since the detailed mechanism
      of (+) strand DNA transfer remains incompletely understood, we developed an in
      vitro system to closely examine this mechanism, composed of HIV 5' RNA, natural
      modified tRNALys,3, synthetic unmodified tRNALys,3 or oligonucleotides (RNA or
      DNA) complementary to the PBS, as well as the viral proteins RT and nucleocapsid
      protein (NCp7). Prior to (+) strand DNA transfer, RT stalls at the double
      stranded tRNA-PBS RNA complex and is able to reverse-transcribe modified
      nucleosides of natural tRNALys,3. Modified nucleoside m1A-58 of natural tRNALys,3
      is only partially effective as a stop signal, as RT can transcribe as far as the
      hyper-modified adenosine (ms2t6A-37) in the anticodon loop. m1A-58 is almost
      always transcribed into A, whereas other modified nucleosides are transcribed
      correctly, except for m7G-46, which is sometimes transcribed into T. In contrast,
      synthetic tRNALys,3, an RNA PBS primer, and a DNA PBS primer are completely
      reverse-transcribed. In the presence of an acceptor template, (+) strand DNA
      transfer is efficient only with templates containing natural tRNALys,3 or the RNA
      PBS primer. Sequence analysis of transfer products revealed frequent errors at
      the transfer site with synthetic tRNALys,3, not observed with natural tRNALys,3.
      Thus, modified nucleoside m1A-58, present in all retroviral tRNA primers, appears
      to be important for both efficacy and fidelity of (+) strand DNA transfer. We
      show that other factors such as the nature of the (-) PBS of the acceptor
      template and the RNase H activity of RT also influence the efficacy of (+) strand
      DNA transfer.

PMID- 9933646
TI  - Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding
      site on the hemopexin carboxyl domain of human gelatinase A by site-directed
      mutagenesis. The hierarchical role in binding TIMP-2 of the unique cationic
      clusters of hemopexin modules III and IV.
AB  - Cell surface activation of progelatinase A occurs in a quaternary complex with
      the tissue inhibitor of metalloproteinases-2 (TIMP-2) and two membrane-type
      matrix metalloproteinases. We have mutated the unique cationic clusters found in
      hemopexin modules III and IV of the carboxyl domain (C domain) of human
      gelatinase A to determine their role in binding TIMP-2. Twelve single, double,
      and triple site-directed mutations were produced that exhibited different TIMP-2
      binding properties. Notably, single alanine substitutions at Lys547 and Lys617
      reduced TIMP-2 binding by an order of magnitude from that of the recombinant wild
      type C domain. Mutations that completely disrupted the C domain.TIMP-2
      interaction were K558A/R561A, K610T/K617A, and K566A/K568A/K617A. A triple
      mutation, K566A/K568A/K575A, having TIMP-2 binding indistinguishable from the
      wild-type C domain (Kd 3.0 x 10(-8) M), showed that simple reduction of net
      positive charge does not reduce TIMP-2 affinity. Because the double mutation
      K566A/K568A also did not alter TIMP-2 binding, these data do not confirm
      previously reported chimera studies that indicated the importance of the triple
      lysine cluster at positions 566/567/568 in TIMP-2 binding. Nonetheless, a subtle
      role in TIMP-2 interaction for the 566/567/568-lysine triad is indicated from the
      enhanced reduction in TIMP-2 binding that occurs when mutations here were
      combined with K617A. Thus, these analyses indicate that the TIMP-2 binding
      surface lies at the junction of hemopexin modules III and IV on the peripheral
      rim of the gelatinase A C domain. This location implies that considerable
      molecular movement of the TIMP-2. C domain complex would be needed for the bound
      TIMP-2 to inhibit in cis the gelatinase A active site.

PMID- 9933647
TI  - Characterization of Raf-1 activation in mitosis.
AB  - We have used site-directed mutagenesis to explore the mechanisms underlying Raf-1
      activation in mitosis, and we have excluded most previously characterized
      activating interactions. Our results indicate that the primary locus of
      activation lies in the carboxyl-half of the molecule, although the extent of
      activation can be influenced by the amino-proximal region, particularly by the
      Raf-1 zinc finger. We also found that Raf-1 is hyperphosphorylated in mitosis at
      multiple sites within residues 283-302 and that these hyperphosphorylations are
      not required for activation. In addition, neither Mek1 nor Mek2 are stably
      activated in coordination with Raf-1 in nocodazole-arrested cells. Overall, the
      data suggest that the mechanism(s) responsible for activating Raf-1 during
      mitosis, and the subsequent downstream effects, are distinct from those involved
      in growth factor stimulation.

PMID- 9933649
TI  - Biochemical and electron microscopic image analysis of the hexameric E1 helicase.
AB  - DNA replication initiator proteins bind site specifically to origin sites and in
      most cases participate in the early steps of unwinding the duplex. The
      papillomavirus preinitiation complex that assembles on the origin of replication
      is composed of proteins E1 and the activator protein E2. E2 is an ancillary
      factor that increases the affinity of E1 for the ori site through cooperative
      binding. Here we show that duplex DNA affects E1 (in the absence of E2) to
      assemble into an active hexameric structure. As a 10-base oligonucleotide can
      also induce this oligomerization, it seems likely that DNA binding allosterically
      induces a conformation that enhances hexamers. E1 assembles as a bi-lobed,
      presumably double hexameric structure on duplex DNA and can initiate bi
      directional unwinding from an ori site. The DNA takes an apparent straight path
      through the double hexamers. Image analysis of E1 hexameric rings shows that the
      structures are heterogeneous and have either a 6- or 3-fold symmetry. The rings
      are about 40-50 A thick and 125 A in diameter. The density of the central cavity
      appears to be a variable and we speculate that a plugged center may represent a
      conformational flexibility of a subdomain of the monomer, to date unreported for
      other hexameric helicases.

PMID- 9933648
TI  - Identification of a novel guanylyl cyclase that is related to receptor guanylyl
      cyclases, but lacks extracellular and transmembrane domains.
AB  - We have identified a novel guanylyl cyclase, named MsGC-I, that is expressed in
      the nervous system of Manduca sexta. MsGC-I shows highest sequence identity with
      receptor guanylyl cyclases throughout its catalytic and dimerization domains but
      does not contain the ligand-binding, transmembrane, or kinase-like domains
      characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C
      terminal extension of 149 amino acids that is not present in other receptor
      guanylyl cyclases. The sequence of MsGC-I contains no regions that show
      similarity to the regulatory domain of soluble guanylyl cyclases. Thus, MsGC-I
      appears to represent a member of a new class of guanylyl cyclases. We show that
      both a transcript and a protein of the sizes predicted from the MsGC-I cDNA are
      present in the nervous system of Manduca and that MsGC-I is expressed in a small
      population of neurons within the abdominal ganglia. When expressed in COS-7
      cells, MsGC-I appears to exist as a soluble homodimer with high levels of basal
      guanylyl cyclase activity that is insensitive to stimulation by nitric oxide.
      Western blot analysis, however, shows that MsGC-I is localized to the particulate
      fraction of nervous system homogenates, suggesting that it may be membrane
      associated in vivo.

PMID- 9933650
TI  - Detection of novel carbohydrate binding activity of interleukin-1.
AB  - Tamm-Horsfall glycoprotein (THGP) and the oligosaccharide fraction liberated from
      THGP by hydrazinolysis inhibited tetanus toxoid-induced T cell proliferation.
      Intact THGP showed approximately 100-fold more inhibitory activity than the free
      oligosaccharides. After fractionating the oligosaccharides by anion-exchange
      column chromatography, the inhibitory activity could be detected in a sialidase
      resistant acidic oligosaccharide fraction (fraction AR). The inhibitory activity
      of fraction AR was not observed when the fraction was added to the T cell culture
      medium 24 h after the addition of tetanus toxoid. Increased concentration of
      interleukin (IL) 1beta and decreased concentration of IL-2 were observed in the T
      cell culture medium after the addition of fraction AR. The oligosaccharides in
      fraction AR also inhibited the growth of an IL-1-dependent cell line, D10-G4.
      These results strongly suggested that the oligosaccharides in fraction AR bind to
      IL-1beta and suppress its cytokine activity. IL-1beta actually bound to the
      fraction AR immobilized on an amino-bonded thin layer plate. Fractionation of the
      oligosaccharides indicated that only oligosaccharides containing an N
      acetylgalactosamine residue and a sulfate residue bound specifically to IL-1beta.
      Removal of either the sulfate residue or the N-acetylgalactosamine residue from
      the oligosaccharides abolished both the proliferation-inhibition and IL-1beta
      binding activities. Since IL-1beta did not bind to thyroid-stimulating hormone,
      which has the sulfate group at C-4 of the N-acetylgalactosamine residue in its N
      linked sugar chains, the binding of IL-1beta toward oligosaccharides in fraction
      AR was considered to be highly specific.

PMID- 9933651
TI  - Hypoxia alters iron-regulatory protein-1 binding capacity and modulates cellular
      iron homeostasis in human hepatoma and erythroleukemia cells.
AB  - Ferritin and transferrin receptor expression is post-transcriptionally regulated
      by a conserved mRNA sequence termed the iron-responsive element (IRE), to which a
      transacting protein called the iron-regulatory protein (IRP) is bound. Our data
      demonstrate that hypoxia powerfully enhances IRE/IRP-1 binding in human cell
      lines. Using the human hepatoma cell line Hep3B as a model, we found that 16 h in
      a 1% oxygen atmosphere markedly increases IRE/IRP-1 binding as assessed by
      electromobility shift assay. Hypoxia also decreased cytosolic aconitase activity.
      The hypoxia-enhanced IRE/IRP-1 binding stabilized the transferrin receptor
      message, increased the cellular mRNA content by over 10-fold, and doubled surface
      receptor expression. Simultaneously, hypoxia suppressed ferritin message
      translation. Hypoxia's effect was most strikingly depicted by the absence of
      ferritin synthesis in cells challenged with inorganic iron. Our results contrast
      with previously reported data (Hanson, E. S., and Leibold, E. A. (1998) J. Biol.
      Chem. 273, 7588-7593) in which a 3% oxygen atmosphere reduced IRE/IRP-1 binding
      in rat hepatoma cells. We discuss some possible reasons for the differences. In
      aggregate with other investigations involving responses to hypoxia, iron, or
      nitric oxide, our data indicate that cellular iron metabolic responses are
      complex and that IRE/IRP-1 interactions vary between cell lines and perhaps
      between species.

PMID- 9933653
TI  - Scientific posters at the EANM annual congress 

PMID- 9933652
TI  - Identification and purification of the rat liver Golgi membrane UDP-N
      acetylgalactosamine transporter.
AB  - Glycosylation of glycoproteins, proteoglycans, and glycosphingolipids occurs
      mainly in the lumen of the endoplasmic reticulum and the Golgi apparatus.
      Nucleotide sugars, donors of all the sugars involved in Golgi glycosylation
      reactions, are synthesized in the cytoplasm and require specialized transporters
      to be translocated into the lumen of the Golgi apparatus. By controlling the
      supply of sugar nucleotides in the lumen of the Golgi apparatus, these
      transporters directly regulate the glycosylation of macromolecules transiting the
      Golgi. We have identified and purified the rat liver Golgi membrane UDP-N
      acetylgalactosamine transporter. The transporter was purified to apparent
      homogeneity by a combination of conventional and dye color chromatography. An
      approximately 63,000-fold purification (6% yield) was achieved starting from
      crude rat liver Golgi membranes and resulting in a protein with an apparent
      molecular mass of 43 kDa. The transporter was active when reconstituted into
      phosphatidylcholine vesicles and could be specifically photolabeled with P3-(4
      azidoanilido)-uridine-5'-[P1-32P]triphosphate, an analog of UDP-N
      acetylgalactosamine. Native functional size determination on a glycerol gradient
      suggested that the transporter exists as a homodimer within the Golgi membrane.

PMID- 9933654
TI  - Multicentre trial on the efficacy and toxicity of single-dose samarium-153
      ethylene diamine tetramethylene phosphonate as a palliative treatment for painful
      skeletal metastases in China.
AB  - A multicentre trial was organized in China as part of an international
      coordinated research project to study the efficacy and toxicity of single-dose
      samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative
      treatment for painful skeletal metastases. One hundred and five patients with
      painful bone metastases from various primaries were treated with 153Sm-EDTMP at a
      dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated
      according to change in daily analgesic consumption, pain score, sum of effect
      product (SEP), Physician's Global Assessment (PGA), blood counts, and organ
      function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in
      group I and 30 of 35 in group II had a positive response, with SEPs of 22.29+/
      14. 47 and 20.13+/-13.90 respectively. Of 72 patients who had been receiving
      analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score
      (KS) increased from 58.54+/-25.90 to 71.67+/-26. 53, indicating improved general
      condition, but the difference was not significant. Among subgroups of patients,
      only those with breast cancer showed a significant change in the Karnofsky score
      after treatment. Inter-group differences were found for net change in KS between
      patients with lung and patients with breast cancer, and between patients with
      lung and patients with oesophageal cancer. Seventeen patients showed no response.
      No serious side-effects were noted, except for falls in the white blood cell
      (nadir 1.5x10(9)/l) and platelet (nadir 6.0x10(10)/l) counts in 44/105 and 34/105
      cases, respectively. Ten patients had an abnormal liver function test. Response
      and side-effects were both independent of dose. In conclusion, 153Sm-EDTMP
      provided effective palliation in 83.8% of patients with painful bone metastases;
      the major toxicity was temporary myelosuppression. Further studies are needed to
      identify better ways of determining the appropriate dose in the individual case
      and the efficacy of treatment.

PMID- 9933655
TI  - Can tumour marker assays be a guide in the prescription of bone scan for breast
      and lung cancers?
AB  - Considering the current need to improve cost-effectiveness in cancer patient
      management, a prospective study was undertaken in order to define the optimal
      combination of bone scan and tumour marker assays in breast and lung cancer
      strategies, as has been done in the case of prostate cancer. All patients with
      breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble
      Teaching Hospital between December 1995 and April 1997 were included. A blood
      sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on
      the same day as the bone scan. Two hundred and seventy-five patients were
      included: 118 with lung cancer and 157 with breast cancer. With regard to lung
      cancer, no information useful for guiding bone scan prescription was obtained
      through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in
      asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value
      chosen as the threshold) is strongly predictive of a negative bone scan; by
      contrast, high tumour marker levels are predictive of neoplastic bone
      involvement. When a doubtful bone scan is obtained in a patient with breast
      cancer, a normal marker level makes it highly probable that bone scan
      abnormalities are not related to malignancy.

PMID- 9933656
TI  - Influence of technetium-99m-hexamethylpropylene amine oxime injection time on
      single-photon emission tomography perfusion changes in epilepsy.
AB  - By digitally computing perfusion changes from ictal or postictal (peri-ictal)
      injections referenced to those acquired interictally, an enhanced method for
      localizing the epileptogenic area is reported. Computer-based image processing
      methods for quantifying regional percent change in the brain are applied to a
      group of 19 epilepsy patients after the injection of technetium-99m
      hexamethylpropylene amine oxime (HMPAO) and after acquiring single-photon
      emission tomography (SPET) data. Each patient's region of epileptogenesis was
      independently localized through pathology and/or successful surgery. The positive
      and negative quantitative perfusion changes were plotted as a function of the
      time of the 99mTc-HMPAO ictal injection. This time scale was normalized relative
      to the seizure duration and is referenced to the time of seizure termination.
      Eight patients, injected ictally, demonstrated perfusion increases of 25%-100% in
      the area of known epileptogenesis. Five patients, injected immediately after
      seizure cessation, demonstrated excessive perfusion decreases of 30%-92%
      associated with the region of seizure onset. Six patients, injected well after
      seizure termination, demonstrated hypoperfusion changes less than 30% at the
      epileptogenic area. Observations on perfusion changes calculated from 99mTc-HMPAO
      SPET scans, as a function of normalized time, support a progression from ictal
      hyper- to excessive hypo-, then finally to persistent interictal hypoperfusion.
      By applying this perfusion pattern model and by noting the time of injection for
      peri-ictal images, an improved method for localizing the epileptogenic area is
      demonstrated.

PMID- 9933657
TI  - The value of renal scintigraphy during controlled diuresis in children with
      hydronephrosis.
AB  - Dynamic renal scintigraphy (DRS) during controlled diuresis is the method of
      choice to diagnose the functional relevance of urinary tract obstruction in
      children with sonographically demonstrated hydronephrosis. However, there are no
      commonly accepted scintigraphic criteria for surgical intervention. On the basis
      of our findings, we propose four stages of washout (WO) of tracer following
      diuresis: in stage I, WO>50%, neither further diagnosis nor intervention is
      necessary; in stage II, 50%>/=WO>/=12%, repetition of DRS is advised within 3-4
      months; and in stage III, 12%>WO>/=5%, DRS should be repeated within 1-2 months.
      Only in stage IV, WO<5%, should surgery be done immediately. This procedure
      reduces surgical interventions by 50% without increasing the risk of residual
      renal damage.

PMID- 9933658
TI  - A PET study of 18FDG uptake in soft tissue masses.
AB  - A study was performed with the aim of investigating some of the methodological
      factors affecting the ability of quantitative 2-[18F]-fluoro-2-deoxy-d-glucose
      (FDG) positron emission tomography to assess tumour malignancy. Twenty-nine
      patients with soft tissue masses were studied using a 6-hour scanning protocol
      and various indices of glucose metabolism were compared with histological grade.
      Significant differences were observed in the time-activity response of benign and
      high-grade tumours. High-grade sarcomas were found to reach a peak activity
      concentration approximately 4 h after injection whereas benign lesions reached a
      maximum within 30 min. This translated to improved differentiation between these
      two tumour types using a standard uptake value (SUV) derived from images acquired
      at later times. An SUV measured 4 h post-injection was found to be as useful an
      index of tumour malignancy as the metabolic rate of FDG determined using either
      Patlak or non-linear regression techniques. Each of these indices had a
      sensitivity and specificity of 100% and 76% respectively for the discrimination
      of high-grade sarcomas from benign tumours.

PMID- 9933659
TI  - Role of attenuation correction for fluorine-18 fluorodeoxyglucose positron
      emission tomography in the primary staging of malignant lymphoma.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been
      shown to improve the diagnostic accuracy in the staging of malignant lymphomas,
      based on the metabolic signal of the lesions. This study was undertaken to
      determine the effect of attenuation correction in the detection of nodal and
      extranodal lesions in the primary staging of malignant lymphomas. Fifty-one
      untreated patients with either non-Hodgkin lymphoma (NHL, n=29) or Hodgkin's
      disease (n=22) were retrospectively evaluated. Static FDG-PET imaging of the
      trunk was performed following administration of 250-350 MBq FDG. Attenuation
      correction was performed in all patients. Images were reconstructed iteratively
      with or without transmission scans. Image evaluation was performed independently
      by two observers, who each examined one set of images (i.e. attenuation-corrected
      or uncorrected). The final decision as to whether results were discordant was
      reached by consensus of both observers. Out of 593 evaluated lymph node regions,
      187 regions of increased FDG uptake were identified by both techniques.
      Differences between the readers concerned mainly the anatomical assignment of
      lesions (n=33) or the status (benign/malignant) of individual lesions (n=24).
      However, direct comparison of the two sets of images demonstrated very similar
      lesion contrast on attenuation-corrected and non-attenuation-corrected images.
      Real differences could be determined only in five regions (neck, 1; mediastinum,
      1; upper abdomen, 3). Thirty-seven extranodal lesions (including lung, liver,
      spleen, bone marrow and soft tissue) were detected by both techniques without
      significant differences. It is concluded that in this study, attenuation
      correction did not improve the diagnostic accuracy of FDG-PET in the detection of
      lymph node or organ involvement during the primary staging of malignant
      lymphomas. Of more importance seemed to be the experience of the reader regarding
      the classification of a lesion's status the anatomical assignment, knowledge of
      physiological uptake and artefacts, and systematic and skillful examination of
      all regions scanned.

PMID- 9933660
TI  - Capabilities of two- and three-dimensional FDG-PET for detecting small lesions
      and lymph nodes in the upper torso: a dynamic phantom study.
AB  - The capabilities and limitations of two-(2D) and three-dimensional (3D) fluorine
      18 fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting small
      tumors and lymph nodes were studied in a phantom modeling the human chest and
      axilla. Multiple dual-radionuclide phantom studies were performed. Five hollow
      spheres ranging in diameter from 3 mm to 15 mm were filled with carbon-11 and
      placed in the axillary and mediastinal regions of an anthropomorphic phantom
      containing hollow organs filled with 18F to simulate FDG uptake 1 h after
      injection. Dynamic imaging was performed to acquire PET images with varying
      target-to-background ratios. Imaging was performed in 2D and 3D acquisition
      modes, with and without attenuation correction, on a modern PET scanner. Lesion
      detectability was visually and quantitatively assessed. For objects larger than 9
      mm in diameter, target-to-background ratios ranging from approximately 3:1 to
      approximately 10:1 were detectable. Objects < 9 mm in diameter required a target
      to-background ratio of >/=18:1. Target-to-background ratios required for lesion
      detectability were equivalent for 2D and 3D PET images with and without
      attenuation correction. In conclusion, 2D and 3D PET with attenuation correction
      consistently detected "tumors" >/= 9 mm. Lesions < 9 mm could be detected if
      there was high enough tumor uptake. No statistically significant differences in
      lesion detection were found for 2D versus 3D PET, or for attenuation-corrected
      versus non-attenuation-corrected images.

PMID- 9933661
TI  - Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor
      imaging in clinically non-functioning pituitary macroadenomas and
      macroprolactinomas.
AB  - We compared pituitary iodine-123 epide- pride single-photon emission tomography
      (SPET) and 123I-IBZM SPET for the in vivo imaging of dopamine D2 receptors in 15
      patients with clinically non-functioning pituitary adenomas. Four patients with
      dopamine agonist-sensitive macroprolactinomas were studied as positive controls.
      The uptake of radioactivity in the pituitary was established using a visual
      scoring system and an uptake index calculated by dividing the average count rates
      in the pituitary area by the average count rates in the cerebellum. All four
      macroprolactinomas showed specific binding of 123I-epidepride, but only one
      showed specific binding of 123I-IBZM. Specific binding of 123I-epidepride was
      demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%),
      but specific binding of 123I-IBZM was shown in only 6 of these 15 cases (40%).
      The uptake of 123I-epidepride in the pituitary region was consistently higher
      than that of 123I-IBZM. None of the patients who showed absence of uptake of 123I
      epidepride in the pituitary area showed uptake of 123I-IBZM in this area. IN
      CONCLUSION: 123I-epidepride SPET is superior to 123I-IBZM SPET for the
      visualization of dopamine receptor-positive pituitary adenomas. Therefore, 123I
      epidepride should replace 123I-IBZM for future D2 receptor SPET studies of
      pituitary adenomas. 123I-epidepride SPET potentially might serve to predict the
      response of clinically non-functioning pituitary adenomas to dopamine agonist
      therapy.

PMID- 9933662
TI  - Positron emission tomographic assessment of "metabolic flare" to predict response
      of metastatic breast cancer to antiestrogen therapy.
AB  - We have investigated whether increased tumor uptake of fluorine-18
      fluorodeoxyglucose (FDG) detected with positron emission tomography (PET) early
      after initiating tamoxifen therapy ("metabolic flare") predicts a hormonally
      responsive breast cancer. Eleven postmenopausal women with biopsy-proved estrogen
      receptor-positive (ER+) metastatic breast cancer were studied by PET with FDG and
      16alpha[18F]fluoro-17beta-estradiol (FES) before and 7-10 days after initiation
      of tamoxifen therapy. FDG and FES uptake was evaluated semiquantitatively in 21
      lesions. The PET results were correlated with follow-up evaluation, continued
      until the patient became unresponsive to hormone therapy (3-24 months). There
      were seven responders and four nonresponders based on clinical follow-up. None of
      the responders had a clinical flare reaction, but all demonstrated metabolic
      flare, with a mean +/- standard deviation increase in tumor standardized uptake
      value (SUV) for FDG of 1.4+/-0. 7. No evidence for flare was noted in the
      nonresponders (change in SUV for FDG -0.1+/-0.4; P = 0.008 vs. responders). The
      degree of ER blockade by tamoxifen was greater in responders (mean decrease in
      SUV 2.7+/-1.7) than in nonresponders (mean decrease 0.8+/-0.5) (P = 0.04). The
      lesions of responders had higher baseline SUVs for FES than did those of three of
      four nonresponders (>/=2.2 vs </=1.7). The findings of a metabolic flare by FDG
      PET and the degree of ER blockade by FES-PET early after institution of tamoxifen
      treatment appear to predict responsiveness to antiestrogen therapy in patients
      with ER+ metastatic breast cancer.

PMID- 9933663
TI  - Sentinel lymph node detection and imaging.

PMID- 9933664
TI  - Gastrointestinal complications of drug therapy.

PMID- 9933665
TI  - Drug-induced disorders of the esophagus.

PMID- 9933666
TI  - Drug-induced disorders of the stomach and duodenum.

PMID- 9933667
TI  - Drug-induced disorders of the small bowel.

PMID- 9933668
TI  - Drug-induced disorders of the colon.

PMID- 9933669
TI  - Anterior and upward displacement of the inferior mesenteric vein:a new diagnostic
      clue to left paraduodenal hernias?
AB  - A 26-year-old man with acute deterioration of recurrent abdominal pain was
      admitted to the hospital. Plain film (abdominal radiographs), spiral computed
      tomography (CT), and barium contrast studies were performed. A left paraduodenal
      hernia causing acute jejunal obstruction was identified on upper gastrointestinal
      barium studies and spiral CT. Pre- and postsurgery examinations were compared,
      and relevant radiological findings were identified. Spiral CT provided excellent
      visualization of the pathognomonic displacement of the inferior mesenteric vein.

PMID- 9933671
TI  - Cytomegalovirus proctitis in a diabetic.
AB  - We describe an unusual case of cytomegalovirus (CMV) proctitis in an elderly
      adult with uncontrolled diabetes mellitus, who had not received immunosuppressive
      therapy. Barium study and computed tomography showed large ulceration and sinus
      tract involving the rectum. CMV colitis is thought to occur almost exclusively in
      immunosuppressed persons. In a nonimmunosuppressed host, the infection is rarely
      reported.

PMID- 9933670
TI  - Intestinal tuberculosis with abdominal complications: radiologic and pathologic
      features.
AB  - BACKGROUND: To investigate radiologic and pathological features of intestinal
      tuberculosis with abdominal complications. METHODS: Twenty-two patients with 23
      surgically proven complications (nine intestinal obstructions, eight
      perforations, three fistulae, and three intestinal bleeds) were analyzed. Medical
      records, radiologic studies, and pathologic examinations were reviewed with
      special emphasis on searching for the common features in each group of
      complication. RESULTS: The most important single feature in seven of the nine
      patients with intestinal obstruction was the presence of stricture. In the
      remaining two patients, bowel adhesion was a primary cause of obstruction. In
      eight patients with intestinal perforation, both obstruction and ulcerations in
      the dilated proximal loop were the important features in six, and multiple deep
      ulcerations without obstruction was a primary cause in the remaining two. The
      common features in three patients with fistulae were focal or multiple
      strictures, severe adhesions, and fibrotic bowel wall. Intestinal bleeding
      originated from diffuse mucosal ulcerations. The abdominal complications occurred
      during antituberculous therapy in 10 of the 22 patients. CONCLUSION:
      Understanding the radiologic and pathologic features of intestinal tuberculosis
      with complications help in making an appropriate clinical decision for the
      treatment strategy. Close observation is necessary, especially in those patients
      who are acutely ill during antituberculous medical therapy. Enteritis-Intestines,
      diseases-Intestines, infection-Intestines, perforation-Intestines, stenosis or
      obstruction.

PMID- 9933672
TI  - Hepatic hemangioma with arterioportal shunts.
AB  - Color Doppler sonograms and angiographic findings in 23 hepatic hemangioma
      patients were compared to clarify how arterioportal shunts influence color
      Doppler findings of hepatic hemangiomas. The results of our study showed that the
      presence of arterioportal shunts (six cases) gave rise to large feeding arteries
      (five cases), multiple intratumoral flows (six cases), and reversal of portal
      flow within (five cases) or around (four cases) the tumor. These color Doppler
      findings mimicked hypervascular malignant tumors. Knowledge of such unusual color
      Doppler findings in hepatic hemangiomas may help in avoiding misinterpretations
      of color Doppler sonograms.

PMID- 9933673
TI  - Small hepatic nodules in cirrhosis: ultrasonographic, CT, and MR imaging
      findings.
AB  - PURPOSE: The purpose of this study was to assess the imaging findings of
      pathologically-proved small hepatic nodules 2 cm in size or smaller detected with
      ultrasonography in cirrhotic patients with suspected hepatocellular carcinoma
      (HCC). MATERIALS AND METHODS: We evaluated sonographically detected 32 small
      hepatic nodules which were pathologically confirmed in 23 consecutive cirrhotic
      patients who were suspected of having HCC. Twenty-six lesions were confirmed with
      ultrasonographically-guided aspiration needle-core biopsy, and six with
      definitive surgery. Ultrasonographic examination records were retrospectively
      reviewed. CT, and MR images obtained with various imaging techniques were
      retrospectively reviewed by two radiologists in a blind fashion. RESULTS: The 32
      hepatic nodules were comprised of seven focal fatty changes, two large
      regenerative nodules, three low-grade dysplastic nodules, five high-grade
      dysplastic nodules, and fifteen HCCs. Ultrasonography showed various echogenicity
      for the hepatic nodules. The signal-intensity characteristics with T1-weighted
      spin-echo, in-phase gradient-recalled-echo, and dynamic MR imagings may be useful
      in distinguishing HCC from nonHCC nodules. CONCLUSIONS: Nearly half of small
      hepatic nodules detected with ultrasonography were nonHCC nodules.
      Ultrasonographic findings may not be reliable in characterizing small hepatic
      nodules in cirrhosis. CT and MR imaging obtained with the various techniques are
      still insensitive to these hepatic nodules.

PMID- 9933674
TI  - Fan-shaped hepatic parenchymal damage after ethanol injection therapy for
      hepatocellular carcinoma: MRI appearances.
AB  - BACKGROUND: T1- and T2-weighted magnetic resonance (MR) images frequently show
      fan-shaped areas of hypo- or hyperintensity in the hepatic parenchyma adjacent to
      a treated hepatocellular carcinoma after percutaneous ethanol injection (PEI)
      therapy. These areas correspond to abnormal contrast enhancement on serial
      dynamic MR images. The purpose of the present study was to describe the location,
      appearance, and frequency of these abnormalities because it is important to
      understand these entities for the correct assessment of therapeutic efficacy.
      METHODS: MR imaging including a multisection dynamic study was performed in 20
      consecutive patients with hepatocellular carcinoma treated with PEI therapy. We
      retrospectively evaluated the presence of fan-shaped hypointensities adjacent to
      treated tumors in the liver parenchyma on T1-weighted images and hyperintensities
      on T2-weighted images and corresponding fan-shaped contrast enhancement on both
      arterial-dominant and delayed-phase dynamic MR images. We review the location,
      appearance, and frequency of these findings, and we discuss the possible causes
      on the basis of pathologic examinations. RESULTS: Seven (35%) of the 20 patients
      showed fan-shaped hyperintense areas adjacent to the treated tumors on T2
      weighted images. These areas showed isointensity in five patients and
      hypointensity in two patients on T1-weighted images. Of these seven patients, one
      (14%) underwent the MR imaging within 1 month after the completion of PEI
      therapy, and six (86%) had it 2-9 months after the completion of PEI therapy
      (mean = 6 months). In all seven patients, fan-shaped hyperperfusion abnormalities
      corresponding to these areas of hyperintensity on T2-weighted images were seen on
      both arterial-dominant and delayed-phase dynamic MR images. Pathologically, the
      coagulative necrosis of the hepatocytes with sinusoidal dilatation and the
      restoration by the development of fibrous tissue were seen in these fan-shaped
      areas. CONCLUSION: The fan-shaped areas of abnormal intensity on T1- and T2
      weighted images and contrast enhancement on dynamic MR images seem to be
      attributable to pathologic changes in the normal liver parenchyma induced by the
      toxic reaction of ethanol. Awareness of the occurrence of such abnormalities in
      the peripheral liver parenchyma adjacent to the treated tumor is important for
      the correct assessment of therapeutic efficacy.

PMID- 9933675
TI  - Measurement of liver volume using spiral CT and the curved line and cubic spline
      algorithms: reproducibility and interobserver variation.
AB  - BACKGROUND: The purpose of this article was to evaluate the accuracy and
      reproducibility of spiral computed tomography (CT) and the curved line and cubic
      spline algorithms in measuring liver volume. METHODS: Spiral CT was performed in
      phantoms, cadaveric liver specimens, and 35 live human subjects (19 healthy
      volunteers and 16 patients). Images were transferred to a workstation, and
      volumes were measured by two observers. One observer repeated the measurements at
      a separate sitting. RESULTS: The correlation between the CT measurement and the
      gold standard measurement of the cadaveric livers was very strong (r = 0.94). For
      the live human subjects, the intraobserver and interobserver correlations were
      extremely high (r = 0.999 and 0.997, respectively). The mean difference in liver
      volume measurements between the separate observations was 1%. CONCLUSION: The
      accuracy and reproducibility of this method of assessing liver volume are very
      high.

PMID- 9933676
TI  - Intrahepatic cholangiocarcinoma with marked hypervascularity.
AB  - Two rare cases of small intrahepatic cholangiocarcinoma with marked
      hypervascularity are reported. Dynamic computed tomographic and magnetic
      resonance images of the two cases revealed strong enhancement of the whole tumor
      on the early phase and prolonged enhancement on the late and delayed phases. In
      both cases, the tumors turned out to be well-differentiated tubular
      cholangiocarcinoma that contained a large number of tumor cells and few
      interstitial fibrous tissues. These results suggest that some intrahepatic
      cholangiocarcinoma should be differentiated from other hypervascular hepatic
      tumors, especially hepatocellular carcinoma, and that prolonged enhancement of
      the tumor on late and delayed phases of dynamic images could be of diagnostic
      value.

PMID- 9933677
TI  - Balloon catheter sphincteroplasty and biliary stone expulsion into the duodenum
      in patients with an indwelling T tube.
AB  - BACKGROUND: To present an alternate approach for treating residual biliary stones
      in patients with indwelling T tube that uses the immature tract created by the T
      tube to carry out both sphincteroplasty and expulsion of the calculi with the
      same angioplasty balloon catheter. METHODS: This technique was performed in five
      patients. Access to the bile duct was through an 8-Fr T tube. First a guidewire
      was inserted and advanced beyond the obstructing stone to the duodenal lumen. The
      T tube was removed over the guidewire, and a balloon catheter was introduced.
      Sphincteroplasty was carried out. Then the balloon was deflated and retracted to
      a position proximal to the stone. It was then reinflated and used to push the
      stone, expelling it into the duodenum. RESULTS: In all cases, all biliary stones
      were expelled without pain, in a single session, and with no immediate
      complications. All patients showed rapid clinical and analytic improvement.
      During clinical and echographic follow-up of 2-22 months (mean = 12.4 months),
      there were no complications or relapses. CONCLUSIONS: Our limited experience
      indicates that sphincteroplasty and expulsion of biliary stones with angioplasty
      balloon catheters through the T tube immature tract is a simple, safe, low-cost
      technique that gives good results.

PMID- 9933678
TI  - Macrocystic serous cystadenoma of the pancreas: CT and endosonographic features.
AB  - Recently, the term "serous cystadenoma" has been adopted in the pathological
      community to qualify the so-called microcystic adenoma of the pancreas. This
      change in terminology was based on the emergence of a new type of serous
      cystadenoma of the pancreas, i.e., the macrocystic variant. We report one case of
      pathologically proven macrocystic serous cystadenoma of the pancreas for which
      the diagnosis of mucinous cystadenoma was suggested preoperatively. This rare but
      benign macrocystic variant exhibits radiological features similar to those of
      mucinous cystadenoma. In addition, inflammatory changes and foci of hemorrhage
      within the tumor may simulate mucinous cystadenocarcinoma.

PMID- 9933679
TI  - Serous cystic neoplasm involving the pancreas and liver: an unusual clinical
      entity.
AB  - Serous cystic neoplasm of the pancreas is typically considered to represent a
      benign pancreatic neoplasm. We present a case where the tumor displayed unusually
      aggressive behavior with metastatic disease to the liver and pancreatic bed.
      Although serous cystic neoplasms should be considered a benign lesion and will be
      cured in most cases by surgical excision, the radiologist should be aware that on
      occasion they can exhibit aggressive behavior.

PMID- 9933680
TI  - Peritoneal serous papillary carcinoma: radiological appearance.
AB  - BACKGROUND: The radiological appearance of peritoneal serous papillary carcinoma
      (PSPC) is described. METHODS: Three cases of PSPC were analyzed retrospectively
      with regard to the radiological appearance and histopathological features.
      RESULTS: All three patients were women, aged 44-71 years. Massive ascites and a
      greater omentum tumor were observed on computed tomography in all patients.
      Double-contrast enema performed in one patient showed irregularity on the upper
      aspect of the transverse colon. Radiological examinations excluded primary tumors
      in both gastrointestinal and genital organs in all patients. Histological
      diagnosis was made from the surgical specimen in two patients and from an autopsy
      specimen in one patient. All patients had a large omental tumor involving the
      transverse colon, but the ovaries were not involved or only minimally involved on
      the surface. Serum CA125 was markedly elevated, and immunohistochemical staining
      for CA125 was positive within the tumor cell cytoplasm in all three patients.
      CONCLUSION: PSPC cannot be diagnosed from radiological findings alone because of
      its similarity to metastatic peritoneal carcinomatosis and peritoneal
      mesothelioma. Marked elevation of serum CA125 may help with PSPC diagnosis.
      Response to treatment is promising, and exploratory laparotomy is thus justified
      when a patient shows characteristic radiological findings and high CA125 level.

PMID- 9933681
TI  - Ileal obstruction caused by idiopathic sclerosing encapsulating peritonitis.
AB  - A 26-year-old woman presented with epigastric pain, vomiting, and a palpable mass
      in the right lower abdomen. Ultrasonography showed a high echogenic mass
      associated with a small amount of ascites in the right lower abdomen. Computed
      tomography demonstrated entrapped ileal loops within a thin-walled fibrous
      capsule. A thin fibrous sac encasing the terminal ileum was detected on
      laparotomy and confirmed as idiopathic sclerosing encapsulating peritonitis.

PMID- 9933682
TI  - Role of duplex color Doppler ultrasound, computed tomography, and MR angiography
      in the diagnosis of septic puerperal ovarian vein thrombosis.
AB  - BACKGROUND: Septic puerperal ovarian vein thrombosis (SPOVT) is one of the
      underlying etiologies of puerperal fever. A correct diagnosis of this condition
      is important because adequate treatment requires additional administration of
      anticoagulants. The purpose of this study was to evaluate the role of duplex
      color Doppler ultrasound (CDUS), computed tomography (CT), and magnetic resonance
      angiography (MRA) in the detection of SPOVT. METHODS: Twenty-six patients with
      puerperal fever suspected to be due to SPOVT and unresponsive to broad antibiotic
      treatment for at least 48 h were included in a prospective study using CDUS, CT,
      and MR imaging including MRA. Examinations were analyzed and then correlated to a
      standard of reference gathered from surgical and clinical follow-up data and from
      results of imaging. RESULTS: SPOVT was present in nine patients (right side n =
      8, bilateral n = 1). CDUS was inconclusive due to gaseous distention of the bowel
      or obesity in 13 of 26 cases. After counting inconclusive findings as wrong
      results for statistical purposes, sensitivity, specificity, and accuracy for CDUS
      were 55.6%, 41.2%, and 46.2%, respectively. CT had a sensitivity of 77.8% with a
      specificity of 62.5%; accuracy was 68.0%. MRA rendered conclusive results in all
      evaluated patients, resulting in a sensitivity and specificity of 100%.
      CONCLUSION: MRA is recommended in all patients with inconclusive CDUS findings
      and persistent suspicion for SPOVT. CT has the advantage of more rapid access and
      lower cost and thus will probably remain a sufficiently accurate alternative.
      Septic puerperal ovarian vein thrombosis (SPOVT)-Computed tomography-Magnetic
      resonance angiography-Ultrasound.

PMID- 9933683
TI  - Retroperitoneal malignant mesenchymoma: imaging findings in five cases.
AB  - BACKGROUND: To describe computed tomographic (CT), magnetic resonance (MR),
      ultrasonographic (US), and angiographic findings of retroperitoneal malignant
      mesenchymoma with emphasis on CT findings. METHODS: Five CT, four US, four
      angiography, and two MR studies were obtained in five patients with
      pathologically proven retroperitoneal malignant mesenchymoma. RESULTS: Tumors
      were larger than 10 cm (n = 4), well-circumscribed and heterogeneous (n = 4), and
      with massive intratumorous calcifications (n = 3) on plain CT or US. Tumors
      showed heterogeneous enhancement on contrast-enhanced CT scans (n = 4) and
      moderate hypervascularity with heterogeneous staining on angiography (n = 3).
      Tumors were essentially hypointense on T1-weighted MR images (n = 2) and
      heterogeneous hyperintense on T2-weighted MR images (n = 2). Plain CT showed a
      fat-dense structure in a tumor in one patient. CONCLUSIONS: The radiologic
      findings of large expansile heterogeneous masses in the retroperitoneum,
      especially with massive calcifications, were considered to be typical of
      malignant mesenchymomas.

PMID- 9933684
TI  - Diagnosis of chronic ectopic gestation by hysterosalpingography.
AB  - Pelvic ultrasound and human chorionic gonadotropin assays are currently the
      standard methodology to detect tubal pregnancy. We report a case of infertility
      investigated by hysterosalpingography in which a clinically unsuspected chronic
      tubal pregnancy was identified with the predisposing factor of bilateral
      salpingitis isthmica nodosa. The radiographic findings of this very rare cause of
      tubal filling defect are shown.

PMID- 9933686
TI  - Abstracts of selected papers from the current literature 

PMID- 9933689
TI  - Pancreatogastrostomy as reconstruction for pancreatoduodenectomy: review.
AB  - A summary of 733 reported cases of pancreatogastrostomy (PG) as a reconstructive
      procedure following pancreatoduodenectomy and the traumatically severed pancreas
      indicates an aggregate leakage rate of 4% over a 52-year period. Although
      mortality rates have declined over this period, the reported high correlation of
      leak with mortality seems to indicate the greater safety of PG over other methods
      for treating the residual pancreatic duct. The lower rate of complications
      related to pancreatocutaneous fistula from PG should correlate with shorter and
      less expensive hospital stays for patients treated with this technique. Several
      questions regarding technique must await further investigation.

PMID- 9933685
TI  - Pelvic congestion syndrome: demonstration and diagnosis by helical CT.
AB  - Pelvic pain is a common gynaecological complaint, sometimes without any obvious
      etiology. We report a case of pelvic congestion syndrome, an often overlooked
      cause of pelvic pain, diagnosed by helical computed tomography. This seems to be
      an effective and noninvasive imaging modality.

PMID- 9933690
TI  - Comparative study of carbohydrate antigen 195 and carcinoembryonic antigen for
      the diagnosis of pancreatic carcinoma.
AB  - The expression CA195 in serum, defined by monoclonal antibody CC3C195 (IgM), was
      studied in 67 patients with pancreatic cancer and in 138 patients with biliary or
      pancreatic benign disease. The results were compared with carcinoembryonic
      antigen (CEA) expression. The overall sensitivity of the CA195 assay (> 12 U/ml)
      was higher than that for CEA (89.5% vs. 53.7%) (p < 0.001). Sensitivity was
      increased to 92.5% with the simultaneous use of the two antigens, but the
      difference was statistically significant only with CEA (p < 0.001). The
      specificity of CA195 calculated from all patients with benign diseases was lower
      than that of CEA (73.1% vs. 89.8%). However, using a cutoff value of 100 U/ml for
      CA195, the specificity of this antigen (82%) was higher than that of CEA. These
      results demonstrate that marked elevations of tumor antigen CA195 are relatively
      specific for pancreatic carcinoma, and that this antigen is superior to CEA for
      diagnosing pancreatic cancer by virtue of its higher sensitivity.

PMID- 9933691
TI  - Solid and papillary epithelial neoplasm of the pancreas in children.
AB  - Solid and papillary epithelial neoplasm of the pancreas is an uncommon low-grade
      malignant tumor found predominantly in young females. In this paper, the authors
      report the tumor's clinical characteristics and the results of surgery in six
      children. Six cases of solid and papillary epithelial neoplasm of the pancreas
      pathologically verified at Seoul National University Children's Hospital between
      1985 and 1997 were retrospectively analyzed. Four were girls and two were boys,
      and their mean age at surgery was 11.2 years (range 8-13 years). All patients
      presented with an abdominal mass and tumor ranging in size from 6.5 x 6.0 cm to
      10.5 x 8.0 cm. Five were located in the head and one in the tail of the pancreas;
      exploration showed that no case involved local invasion or metastasis. All
      patients underwent complete resection, which involved five
      pancreaticoduodenectomies and one distal pancreatectomy. No patient died during
      surgery, and after a mean follow-up period of 5.5 years (range 1.5-12.5 years)
      all were alive with no recurrences. We believe that the malignancy of this tumor
      is low grade and that the prognosis is good. For a neoplasm arising anywhere in
      the pancreas, complete resection is the treatment of choice. Solid and papillary
      epithelial neoplasm of the pancreas of children shows less female preponderance
      in children than in adults.

PMID- 9933692
TI  - Gelatinase A and membrane-type 1 matrix metalloproteinase mRNA: expressed in
      adrenocortical cancers but not in adenomas.
AB  - In an attempt to understand the mechanism behind the invasion and metastasis in
      adrenocortical cancer we performed mRNA in situ hybridization on 30 tumors for
      three matrix metalloproteinases (MMPs): gelatinase A, membrane type 1 matrix
      metalloproteinase (MT1-MMP), and collagenase-3. All are known to participate in
      the invasion and metastasis of other tumor forms by degrading the extracellular
      matrix. Thirteen of sixteen cancers, but only one of fourteen benign lesions
      showed expression of gelatinase A, which was localized in stromal cells. MT1-MMP
      is thought to assist in tumor invasion and metastasis by activating the zymogen
      gelatinase A. Of 14 malignant tumors analyzed, 12 showed MT1-MMP mRNA expression,
      which in 7 cases was detected in both neoplastic and stromal cells. The benign
      tumors showed MT1-MMP expression in only 3 of 11 cases, and it was restricted to
      tumor cells. Fourteen tumors (11 cancers, 3 adenomas) were also analyzed for
      collagenase-3 mRNA, but no expression was detected. In conclusion, our data show
      that gelatinase A mRNA is expressed in most malignant adrenocortical tumors but
      not in the benign tumors. Gelatinase A mRNA expression is restricted to stromal
      cells, whereas its activator, MT1-MMP, is expressed in both stromal and
      neoplastic cells. Inhibition of gelatinase A and other proteinases may in the
      future become important as a form of cancer treatment.

PMID- 9933694
TI  - Surgical strategy for abdominal aortic aneurysm with concurrent symptomatic
      malignancy.
AB  - In an attempt to improve the guidelines for concurrent management of concomitant
      abdominal aortic aneurysm (AAA) and symptomatic malignancy, a retrospective study
      was undertaken. A total of 186 AAA repairs were performed electively, and 25
      patients (13.4%) had concurrent symptomatic malignancy from April 1986 to March
      1997. Fourteen patients underwent a one-stage operation, including five
      abdominoperineal rectal resections, four subtotal gastrectomies, three total
      gastrectomies, and two right hemicolectomies. Eleven others underwent a two-stage
      operation, including four with total gastrectomy and left hemicolectomy followed
      by AAA repair, as well as two with right hemicolectomy and one with left
      hemicolectomy prior to AAA repair. There were no operative deaths or severe
      postoperative complications. Of the 25 patients, 22 (88.0%) are still alive
      during follow-up ranging from 8 months to 11 years. Our surgical approach to both
      lesions is as follows: (1) Using the transperitoneal approach alone, subtotal
      gastrectomy and abdominoperineal rectal resection can be safely done
      simultaneously. (2) Although total gastrectomy can also be performed
      concurrently, the approach used for each lesion is separate. (3) Colorectal
      resection is generally done separately. However, a one-stage operation can be
      performed using the thromboexclusion procedure for AAA repair in patients with
      right-sided colonic cancer or a temporary transverse colostomy for left-sided
      colorectal cancer.

PMID- 9933693
TI  - Mesenteric infarction after aortoiliac surgery on the basis of 1752 operations
      from the National Vascular Registry.
AB  - The present nationwide, multicenter clinical study was carried out in 26
      departments of surgery to define the incidence and attendant mortality of
      intestinal infarction following abdominal aortic surgery, and to identify
      patients at risk of it. The data consist of 1752 patients who underwent abdominal
      aortic reconstruction during 1991-1993 as recorded in the Finnish national
      vascular registry (FINNVASC). Among the 1752 operations, 27 patients treated at
      14 different hospitals had intestinal ischemia, and the complete patient records
      of all 27 cases were reanalyzed. The incidence of bowel infarction was 1.2%.
      Among patients operated on for a ruptured aneurysm it was 3.1%, whereas 1.0% of
      patients with nonruptured aneurysm and 0.6% of those operated on for aortoiliac
      occlusive disease developed intestinal infarction. In 14 patients (67%) the
      lesion affected the left colon. The overall 30-day mortality rate was 13% but
      reached 67% among those with intestinal infarction. We conclude that acute
      intestinal ischemia with bowel infarction is an infrequent but serious
      complication of abdominal aortic surgery. It is mainly related to surgery due to
      aneurysmal disease, and patients with occlusive aortoiliac disease present
      ischemic complications in the intestines less often. Hypotensive patients being
      treated for ruptured aneurysm are at greatest risk of intestinal ischemia.

PMID- 9933695
TI  - Distal pulse palpation: is it reliable?
AB  - The aim of this study was to evaluate the reliability of distal pulse palpation.
      The dorsalis pedis and the tibialis posterior arteries of 25 patients with
      suspected lower limb arterial disease were independently palpated by three
      vascular surgeons and three medical students in the outpatient clinic and by two
      vascular nurses and one physician in the vascular laboratory. The palpation
      findings were compared to the ankle/brachial index (ABI). Palpable and unpalpable
      pulses were best separated with ABI 0.76 as the cutoff point. The degree of
      misdiagnosis was unacceptably high, with an underdiagnosis of more than 30%. The
      agreement was highest (kappa 0. 68, good) among the vascular laboratory personnel
      in the peaceful vascular laboratory and lowest (kappa 0.38, fair) among the
      vascular surgeons in the busy outpatient clinic. The poor agreement and the high
      proportion of misdiagnosis obtained in the outpatient clinic argue against the
      use of pulse palpation as a single diagnostic method. Palpable pulses with low
      ABIs clearly state the need for more objective measurements whenever ischemia is
      suspected. Yet, by carefully palpating both pedal arteries under good, nonhurried
      conditions the reproducibility and accuracy of pulse palpation can be tolerable.

PMID- 9933697
TI  - Plain abdominal radiography as a routine procedure for acute abdominal pain of
      the right lower quadrant: prospective evaluation.
AB  - The aim of this prospective study was to determine whether plain abdominal
      radiographs (PAX) are helpful in the management of adult patients presenting with
      acute pain of the right lower quadrant (RLQ). A questionnaire was filled in for
      each patient admitted to our hospital for acute abdominal pain of the RLQ, before
      and after PAX were obtained. The initial questionnaire indicated the suspected
      diagnosis and a provisional therapeutic option. A total of 104 consecutive
      patients were included in this study, 76 of whom underwent surgery. The negative
      laparotomy rate was 22%. PAX changed the suspected diagnosis and management for
      six patients (6%), leading in one case to negative laparotomy. Of the remaining
      five patients, three were operated (two for acute appendicitis and one for small
      bowel obstruction), and two were treated conservatively for ureteral calculi.
      This prospective study seems to demonstrate that the indiscriminate use of PAX is
      not helpful for most patients with acute pain of the RLQ. However, it may be
      performed in selected patients with clinically suspected small bowel obstruction
      or urinary symptoms.

PMID- 9933696
TI  - Thoracic epidural anesthesia for pain relief and postoperation recovery with
      modified radical mastectomy.
AB  - The purpose of this study was to investigate whether thoracic epidural anesthesia
      (TEA) provides better postoperative pain relief and recovery than general
      anesthesia (GA) for modified radical mastectomy (MRM) surgery. Sixty-four
      patients rated as American Society of Anesthesiologists (ASA) 1 to 3 who
      underwent MRM surgery were included in the study. In TEA group patients, 2%
      lidocaine (15-20 ml) was administered via the epidural route as primary
      anesthesia, in conjunction with midazolam (5-10 mg) and fentanyl (<250 microg)
      for amnesia. The GA patients were maintained with isoflurane and 50% nitrous
      oxide in oxygen. After operation the patients were given pethidine (1 mg/kg IM)
      as required for pain relief. The time to first pethidine requirement, total
      pethidine consumption, worst pain score, bed rest time, satisfaction score, and
      anesthesia-related side effects were recorded for 2 days after surgery. The
      results show that TEA provided a more prolonged analgesic effect than GA after
      operation. A longer time to first pethidine requirement (19.2 +/- 1.5 vs. 7.6 +/-
      2.5 hours) (p < 0. 001) and decreased pethidine consumption (17.2 +/- 7.0 vs.
      76.3 +/- 17.4 mg) (p < 0.001) were observed in the TEA group than in the GA
      group, respectively. A worse visual analog scale (VAS) pain score was observed in
      the GA group (5.7 +/- 0.6) than in TEA patients (4.3 +/- 0.4) (p < 0.01). The
      average bed rest time was significantly shorter in the TEA group (16.9 +/- 0.9
      hours) (p < 0.01) than in the GA group (27.1 +/- 4.1 hours). Overall satisfaction
      scores were significantly higher in the TEA group (4.4 +/- 0.1) (p < 0.01) than
      in the GA group (3.5 +/- 0.2). Side effects were observed at a higher frequency
      in the GA group (16/32) (p < 0.0001) than in the TEA group (3/32). The frequency
      of pethidine injection for pain relief was significantly lower in the TEA group
      (8/32) (p < 0.0001) than in the GA group (24/32). The total hospital cost (NT
      64,392 +/- 3,523 vs. NT 53,806 +/- 2,817) (p = 0.0342) and anesthesia cost (NT
      7,968 +/- 246 vs. NT 5,268 +/- 262) (p < 0.0001) are also significantly lower in
      the TEA group than the GA group. In conclusion, TEA provided better postoperative
      pain relief and recovery and lower cost than GA for MRM surgery.

PMID- 9933698
TI  - Noninvasive evaluation of blunt abdominal trauma: prospective study using
      diagnostic algorithms to minimize nontherapeutic laparotomy.
AB  - A prospective study was performed to investigate the feasibility and benefit of
      evaluating blunt abdominal trauma (BAT) without diagnostic peritoneal lavage
      (DPL) or other invasive methods. Diagnostic algorithms were designed by using
      ultrasonography (US) as a screening method. For unstable patients, a free fluid
      >/= 2 mm thickness on US images over any one of the intraperitoneal spaces
      (bilateral subphrenic, Morrison, and Douglas pouch) was used as an indicator for
      laparotomy. For stable patients, any intraabdominal free fluid detected by US was
      used as an indicator for further investigations. Computed tomography served as a
      principal complementary method. To further clarify the clinical results, the rate
      of nontherapeutic laparotomy (NTL) was compared with that from a previous 5-year
      review done before this study. During studying period of 1 year, 170 patients
      were consecutively enrolled. There was no delayed diagnosis, and 66 patients were
      found to have BAT; 17 patients were initial unstable, among whom 15 had free
      fluid shown by US and 13 patients had confirmed BAT. Eight of the unstable
      patients with free fluid on US were saved from NTL, of whom six had
      retroperitoneal hematoma. There was no NTL in unstable patients. Twenty-two
      patients underwent laparotomy. Two laparotomies done for a suspicion of bowel
      injury turned out to be NTL. The rate of NTL in the present study was significant
      lower than that in a previous review (9.1% vs. 32.2%, p = 0.025). Hence following
      well designed algorithms, noninvasive evaluation of BAT can proceed with safety,
      and NTL is minimized.

PMID- 9933699
TI  - Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for
      esophageal carcinoma.
AB  - Transhiatal esophagectomy (THO) may be a valid alternative to the traditional
      Ivor Lewis (ILO) procedure, but there have been reservations about procedure
      mortality, nodal clearance, and survival. ILO is preferred for bulky
      midesophageal lesions and THO in frail patients, making randomization difficult.
      This retrospective study compares results of a 10-year period from January 1985
      with a minimum follow-up period of 12 months. Four patients were lost to follow
      up. Preoperative nutritional markers were similar in the two groups, as were the
      age and sex distribution. Altogether 33 ILOs and 65 THOs were performed. TNM
      staging was similar between groups, there being 43% stage II and 45% stage III
      lesions among the ILO patients and 53% stage II and 32% stage III disease in the
      THO group. Operating time was shorter for THO (256 +/- 58 minutes vs. 279 +/- 50
      minutes) (p = 0.05); if two surgeons operated concurrently, THO could be
      performed 40 minutes quicker than THO or ILO performed by a single surgeon (p =
      0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7
      days for THO (p = 0.014). The 30-day mortality was 5.1%; total in-hospital
      mortality was 7.1% with no difference for operation type. There were similar
      morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no
      significant effect of surgical technique; there were no apparent advantages for
      either operation when patients were compared by tumor type or matched for stage.
      Hence THO is a valid alternative to ILO, particularly for stage II and III
      cancer.

PMID- 9933700
TI  - Adenocarcinoma of distal esophagus and gastroesophageal junction: long-term
      results of surgical treatment in a North Indian Center.
AB  - This retrospective study reports our experience managing 78 patients with
      adenocarcinoma of the esophagus and gastroesophageal junction operated between
      January 1982 and December 1996. Altogether 18 patients presented with stage I and
      II disease, and 60 patients had stage III and IV disease at presentation; 56
      patients (71.8%) were found to have resectable disease. Of these, transhiatal
      esophagectomy was possible in 51 patients. Transthoracic esophagectomy was done
      in 3 patients, and a left thoracoabdominal approach was used in 2 patients. The
      stomach was used as conduit in 50 patients and the colon in 6 patients. Twenty
      two patients were found to have unresectable lesions at laparotomy and underwent
      various palliative procedures. Overall operative mortality was 6.3%. Mortality in
      the resectable group was only 3.6%. Follow-up ranges from 3 to 128 months, with
      four patients lost to follow-up at 1, 6, 8, and 10 months. The 5-year survival of
      the whole group according to Kaplan and Meier survival analysis was 21.27% with a
      median survival of 13.48 months. Univariate analysis using the log-rank test
      revealed stage of the disease and resectability to be significant predictors of
      survival. On multivariate analysis, curative resection appeared to be the most
      significant predictor of survival in patients undergoing resection.

PMID- 9933701
TI  - Type-oriented intraoperative and adjuvant chemotherapy and survival after
      curative resection of advanced gastric cancer.
AB  - Recent observations and our experience that histologic types of gastric cancer
      related significantly to patterns of recurrence prompted us to develop
      intraoperative and postoperative chemotherapy based on the preoperatively
      diagnosed histologic types of cancer and to evaluate its effectiveness by a
      prospective randomized trial. This chemotherapy regimen consisted of the
      intraoperative administration of mitomycin C (MMC) and postoperative
      administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT)
      (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were
      randomly assigned to one of three treatment groups: no intraoperative
      chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy
      and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17).
      Patients with an intestinal type of cancer were randomly assigned to one of three
      treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was
      subjected to the same protocols as the P0, P1, and P2 groups, respectively,
      except for the MMC administration route. MMC (10 mg/patient) was administered
      intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal
      vein (H1 and H2 groups). All patients underwent curative resection. Background
      factors did not differ significantly among the treatment groups. The overall
      survival rates were progressively worsened in the order of P2, P1, and P0 or H2,
      H1, and H0, respectively. The survival rate of the P2 group was statistically
      higher than that of the P0 group (p < 0.05). The intermediate-term survival rate
      of the P2 group or H2 group was significantly higher than that of the P0 group (p
      < 0.05) or H0 group (p < 0.05), respectively. These results suggest the
      effectiveness of this therapy and the possible eradication of potential
      micrometastatic foci outside the surgical field by the direct administration of
      chemotherapeutic agents to the predicted recurrence site.

PMID- 9933702
TI  - Preoperative transcatheter arterial chemoembolization and prognosis of patients
      with hepatocellular carcinomas: retrospective analysis of 120 cases.
AB  - To clarify whether preoperative transcatheter arterial chemoembolization (TAE)
      improves the prognosis of patients with hepatocellular carcinoma (HCC) after
      surgery, 120 patients who had undergone hepatectomy for HCC from 1988 to 1994 and
      satisfied the criteria of stages II and III were enrolled in this study. Forty
      four patients underwent preoperative TAE (group A) and 76 patients did not (group
      B). No significant differences in the outcomes were observed between these two
      groups. To rectify the comparison, patients with tumors 2 to 8 cm were assigned
      to groups A1 (n = 24) and B1 (n = 57), and those with tumors > 8 cm were assigned
      to groups A2 (n = 20) and B2 (n = 19), respectively. Although no significant
      differences in survival between groups A1 and B1 were found, group A2 presented
      superior 1-, 2-, and 3-year tumor-free survival rates of 80%, 55%, and 32% and 1
      , 3-, and 5-year cumulative survival rates of 90%, 53%, and 42%. These figures
      are in comparison with the tumor-free survival rates of 50%, 22%, and 11% (p =
      0.06), and the cumulative survival rates of 72%, 33%, and 11% (p = 0.01) during
      the same periods for group B2, respectively. The Cox regression model revealed
      that for patients with tumors > 8 cm, the relative risk of preoperative TAE for
      overall survival was 0.38 (p = 0.017), indicating that preoperative TAE might
      benefit patients with tumors > 8 cm but not those with tumors 2 to 8 cm.

PMID- 9933703
TI  - Characteristics of hepatocellular carcinoma in patients with negative virus
      markers: clinicopathologic study of resected tumors.
AB  - Fifty-one cases of resected hepatocellular carcinoma (HCC) were retrospectively
      analyzed to evaluate the clinicopathologic features of HCC in patients with
      negative virus markers. The data were compared between three groups: hepatitis B
      surface antigen positive (HB, n = 11), hepatitis C virus antibody positive (HC, n
      = 21), and non-BC (both HbsAg and HCVAb negative, n = 12). Seven patients were
      excluded from the study because of operative death (n = 3), a history of alcohol
      abuse (n = 3), or the presence of dual positive HB and HC virus markers (n = 1).
      The data were analyzed by either an analysis of variance (ANOVA) or a contingency
      table. The age of the non-BC patients was higher (63.0 +/- 4.1, +/- SE) than that
      of HB patients (54.0 +/- 3.2, p < 0.05) but was identical to that of the HC group
      (62.0 +/- 1.8). Among the preoperative laboratory data, the serum glutamic
      oxaloacetate and glutamate pyruvate transaminoses (GOT, GPT) levels were
      statistically lower in the non-BC patients (32.8 +/- 4.8 and 28.0 +/- 4.4 IU/L,
      respectively) than in the HB and HC patients. The pathologic features of the
      resected specimens in the non-BC patients showed more invasive growth than in
      specimens from the HB or HC patients. The clinical stages (defined based on the
      criteria of the Japanese Association of Hepatocellular Carcinoma) were also more
      advanced in the non-BC patients than in the other groups. Postoperative survival
      time showed no significant difference among the groups. In conclusion, the non-BC
      patients had comparatively greater invasive growth and more advanced clinical
      stages than the HB and HC patients, despite the absence of liver cirrhosis, and
      so demonstrated the same poor survival data as observed in the HB and HC
      patients.

PMID- 9933704
TI  - Effective hepatic cryoablation: does it enhance tumor dissemination?
AB  - This experimental study was designed to investigate the risk of tumor
      dissemination by hepatic cryosurgery and to determine the final subzero
      temperature required for effective hepatic tumor cryoablation. Although
      cryosurgery is now one of the established modalities for the treatment of some
      liver tumors and has been used for two decades, controversy remains regarding the
      final subzero temperature needed to destroy tumor masses. One experimental report
      has indicated that hepatic cryosurgery may enhance tumor dissemination. For this
      study, rat hepatic tumors were produced by direct injection of rat colonic
      carcinoma cells (DHD/K12/TRb). The control untreated animals (n = 12) were
      sacrificed after induction of liver tumors at 4 and 6 weeks. The animals in the
      treatment group (n = 16) underwent cryosurgery 2 weeks after tumor induction and
      were allowed to recover before sacrifice 2 and 4 weeks later. Pulmonary
      metastases were identified in 9 of 12 (75%) control animals at postmortem
      examination (2 and 6 weeks after tumor inoculation) and in 6 of 16 (38%) rats in
      the treatment group at sacrifice 2 and 4 weeks after cryosurgery (p = 0.11,
      Fisher's test for unpaired analysis). Peritoneal deposits were observed in 5 of
      12 (42%) control animals at postmortem examination and in 8 of 16 (50%) of the
      treated animals at the time of cryosurgery (p = 0.95, Fisher's test for unpaired
      analysis). Two other study animals developed deposits after cryosurgery. The
      prevalence of peritoneal deposits in the study group was not altered by
      cryosurgery (p = 0.5, McNemar's test for paired analysis). The importance of the
      final subzero temperature at the edge of the iceball during tumor ablation by
      cryosurgery was confirmed by the histologic findings. Complete ablation with no
      residual viable tumor was obtained only when the subzero temperature had reached 
      38 degrees C or below. The results of this study do not support the suggestion
      that hepatic cryosurgery enhances tumor dissemination. The findings also confirm
      that a subzero temperature at the edge of the iceball of -38 degrees C or lower
      is necessary to ensure complete ablation of tumor.

PMID- 9933726
TI  - A review of water balance in ageing in health and disease.
AB  - The elderly are at increased risk of changes in body water and sodium, often
      accompanying comorbid disease states, which are associated with increased
      mortality. The clinical assessment of the hydration status of an elderly patient
      is difficult and the elderly care physician relies on both the clinical picture
      and laboratory investigation. Although still contentious, research suggests that
      the elderly may appreciate thirst less readily. However, healthy elderly may be
      able to produce an enhanced vasopressin response to osmotic stimulation compared
      to their younger counterparts, possibly in response to reduced renal function.
      The changes in these systems, when combined with coincident disease, place
      elderly patients at risk of water imbalance and electrolyte disturbance.

PMID- 9933705
TI  - Tribute to a triad: history of splenic anatomy, physiology, and surgery--part 1.
AB  - The spleen is an enigmatic organ with a peculiar anatomy and physiology. Though
      our understanding of this organ has improved vastly over the years, the spleen
      continues to produce problems for the surgeon, the hematologist, and the patient.
      The history of the spleen is full of fables and myths, but it is also full of
      realities. In the Talmud, the Midrash, and the writings of Hippocrates, Plato,
      Aristotle, Galen, and several other giants of the past, one can find a lot of
      Delphian and Byzantine ambiguities. At that time, splenectomy was the art of
      surgery for many splenic diseases. From antiquity to the Renaissance, efforts
      were made to study the structure, functions, and anatomy of the spleen. Vesalius
      questioned Galen; and Malpighi, the founder of microscopic anatomy, gave a sound
      account of the histology and the physiologic destiny of the spleen. Surgical
      inquiry gradually became a focal point, yet it was still not clear what purpose
      the spleen served. It has been within the past 50 years that the most significant
      advances in the knowledge of the spleen and splenic surgery have been made. The
      work of Campos Christo in 1962 about the segmental anatomy of the spleen helped
      surgeons perform a partial splenectomy, thereby avoiding complications of
      postsplenectomy infection. With the recent successes of laparoscopic splenectomy
      in selected cases, the future of splenic surgery will undoubtedly bring many more
      changes.

PMID- 9933727
TI  - Differential effects of pharmacological doses of melatonin on malondialdehyde and
      glutathione levels in young and old rats.
AB  - BACKGROUND: The free radical theory of aging suggests the oxygen-derived species
      as the causative agents and free radical scavengers as the defense systems in
      aging process. The exact role of the free radical scavenging effects of melatonin
      in aging remains to be clarified. OBJECTIVE: In this experimental study, we
      investigated the age-related changes of malondialdehyde (MDA), a lipid
      peroxidation product, and glutathione (GSH) and the effects of exogenous
      melatonin. METHODS: Plasma, liver, and lung MDA and GSH levels of 9- and 28-month
      old rats were measured. RESULTS: Plasma, lung, and liver MDA levels of old rats
      were significantly higher than those of the young ones (p = 0.024, p = 0.005, and
      p = 0.0007, respectively). However, while the lung GSH levels were found to be
      significantly decreased in the control group of old rats as compared with young
      ones (p = 0.005), the liver GSH levels were unchanged. Plasma MDA levels were
      found to be significantly lower in the melatonin group of old rats as compared
      with the control group (p = 0.020) but lung and liver MDA levels were not
      significantly different. There were no significant differences in the levels of
      measured parameters between both groups of young rats. CONCLUSION: Our results
      suggest that increased levels of lipid peroxidation products may have a role in
      aging, and exogenous melatonin may delay the aging process of tissues by means of
      its free radical scavenging effects.

PMID- 9933728
TI  - Increase of the cellular growth of old human diploid fibroblasts by radical
      scavenger: water-soluble protein from broad beans.
AB  - There is increasing evidence that free radical scavengers play an important role
      in the aging process and the control of cellular growth. We purified a free
      radical scavenging protein, the water-soluble protein (WSP) from broad beans
      (Vicia faba). In this study, we examined the effect of WSP on cellular growth and
      in vitro life span in old human fetal lung fibroblasts (WI-38 and PDL 37-40, 78
      84% of the maximum life span). Since WSP increased the cellular growth, we also
      examined the effect of WSP (1.25-5 microg/ml) on cytosolic antioxidant enzyme
      activities in the old cells treated or not with tert-butyl hydroperoxide (BHP) to
      elucidate the mechanisms of cell proliferation in the old cells. The cellular
      growth of old fibroblasts was greatly increased by WSP. In 1.25 and 2.5 microg/ml
      of WSP, the cell proliferation increased by 32 and 35%, respectively, as compared
      with controls. The maximum population doubling levels of the cells did not
      increase. In the cells incubated with BHP, the cytosolic superoxide dismutase
      activity was returned to its control value by WSP treatment (1.25-5 microg/ml).
      The cytosolic glutathione peroxidase activity progressively increased with
      increasing concentrations of WSP. On the other hand, the cytosolic superoxide
      dismutase activity after 1.25- and 2.5- microg/ml WSP treatment without BHP was
      increased by 189 and 144%, respectively. Similarly, the cytosolic glutathione
      peroxidase activity was increased by 67 and 53%, respectively. These results
      suggest that cytosolic antioxidant activities in old cells can be modulated by
      WSP treatment. We concluded that there was a correlation between the optimum WSP
      concentrations for the increase of cellular growth and the WSP concentrations
      required to exhibit these maximum enzyme activities.

PMID- 9933729
TI  - Age-related changes on glucose transport and utilization of human erythrocytes:
      effect of oxidative stress.
AB  - BACKGROUND: Normal aging is associated with an impairment in glucose homeostasis.
      METHODS: In order to investigate the effect of aging on glucose transport and
      utilization in erythrocytes, the transport and utilization of glucose were
      measured in erythrocytes from 10 young (mean age 26 +/- 3 years) and 10 elderly
      (mean age 70 +/- 7 years) healthy individuals. In addition, the glucose transport
      and utilization were also measured in the presence of cumene hydroperoxide
      (CumOOH), a toxic organic hydroperoxide that is known to induce oxidative stress.
      RESULTS: The levels of glucose transport and utilization were significantly lower
      in the elderly group than the young group (p < 0.05). The glucose transport and
      utilization were not altered by CumOOH treatment in either young or elderly
      individuals. CONCLUSION: These results indicate an age-related decrease in the
      both glucose transport and utilization in erythrocytes.

PMID- 9933730
TI  - Do all systems age together?
AB  - BACKGROUND: Aging changes in different body system are well described, but few
      studies have considered the relationship between them. OBJECTIVE: The purpose of
      this study was, therefore, to investigate the interrelationships between markers
      of aging in different parts of the body. METHODS: A cross-sectional study design
      was used. Structural and functional markers of aging were measured in a number of
      different body systems. RESULTS: Conditional independence analysis demonstrated
      that the aging markers selected clustered into two groups, either related to
      chronological age or adult height. Visual acuity, lens opacity, hearing
      threshold, cognitive decline, and the number of teeth were associated with age,
      while systolic blood pressure and skin thickness were related to height. Grip
      strength was associated with both. CONCLUSIONS: The differential associations of
      the aging markers with chronological age and adult height suggest that different
      systems do not age together. This may have relevance for understanding what
      underlies aging, and these preliminary findings now require replication in other
      aging cohorts.

PMID- 9933731
TI  - Cognitive impairment among elderly coronary heart disease patients.
AB  - BACKGROUND: Coronary heart disease (CHD) and decline in cognitive functioning and
      dementia are common problems in the elderly. Cardiovascular diseases (CVDs) are
      connected with vascular dementia, but less is known about cognitive functioning
      among elderly patients with CHD based on population studies. OBJECTIVE: To
      describe the associations between CHD and cognitive impairment among the elderly.
      POPULATION AND METHODS: Of the total population of the Lieto study (488 community
      dwelling men and 708 women, >/=64 years old), the ambulatory patients with CHD
      (89 men and 73 women) and sex- and age-matched controls without any sign of CHD
      (178 men and 146 women) were selected to make up the study population. CHD was
      defined as the presence of angina pectoris or a past myocardial infarction.
      Cognitive assessment was based on the Mini-Mental State Examination (MMSE).
      RESULTS: The total MMSE scores, the MMSE subtest scores and the overall test
      based cognitive functioning did not differ between patients and controls. Among
      men, higher MMSE subscores in orientation and language were related to more
      severe chest pain. According to logistic regression analyses, the cognitive
      impairment of men was associated with high age, the use of cardiac glycosides and
      physical disability. Among women, cognitive impairment was associated with high
      age and the use of antipsychotics. CONCLUSION: In general, CHD has no independent
      association with cognitive impairment among the non-institutionalized community
      living elderly. Among men, however, a complicated CHD may negatively affect
      cognitive functioning.

PMID- 9933732
TI  - Clinical relevance of thiamine status amongst hospitalized elderly patients.
AB  - BACKGROUND: The prevalence and the consequences of thiamine deficiency among
      elderly patients admitted to acute geriatric wards are not known. OBJECTIVES: (1)
      To assess the prevalence of thiamine deficiency in patients admitted to a
      geriatric ward compared to age-matched ambulatory outpatients; (2) to identify
      their diseases and problems associated with thiamine deficiency, and (3) to
      determine the relationship between the thiamine status and the cognitive and
      functional status of these patients. MATERIALS AND METHODS: 118 aged hospitalized
      patients (83 +/- 7 years; mean age +/- SD) were prospectively enrolled on
      admission to the geriatric ward. Their cognitive status was assessed using the
      Mini-Mental State Examination (MMSE) and their ability to perform their
      activities of daily living (ADL) using ADL scales. The effect of exogenous
      thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity
      (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data,
      diseases and treatment were identified as potential associated risk factors. This
      group of hospitalized patients was divided according to their thiamine status to
      characterize the conditions associated with thiamine deficiency. Thirty-five
      outpatients without any functional or cognitive impairment served as a control
      group. RESULTS: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of
      >15%, and 6 with values of >22%, indicating moderate and severe thiamine
      deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK
      effect of >15% and none of them reached values of >18%. Although it tended to be
      lower in outpatients, the mean TPP TK effect did not statistically differ from
      the mean of inpatients. Thiamine-deficient inpatients comprised a larger
      proportion of institutionalized subjects than nondeficient inpatients (87 versus
      47%, p < 0.001). Functional status, cognitive functions and the occurrence of
      delirium did not differ according to their thiamine status. By contrast, thiamine
      deficient inpatients exhibited a higher proportion of Alzheimer's disease,
      depression, cardiac failure and falls. Furosemide was more frequently taken by
      thiamine-deficient patients. CONCLUSIONS: Severe thiamine deficiency remained
      quite low among the hospitalized elderly. The prevalence of moderate thiamine
      deficiency approached 40%. Institutionalized subjects were at particular risk of
      developing thiamine deficiency. Its clinical relevance on functional status and
      on cognitive function remained not significant. By contrast, a high proportion of
      falls, Alzheimer's disease, depression, cardiac failure and furosemide use could
      have been related to thiamine deficiency.

PMID- 9933733
TI  - Aging and the scope of visual attention.
AB  - OBJECTIVE: To discover whether some cognitive deficits associated with aging
      could be related to a restricted scope of visual attention. DESIGN: Cross
      sectional study, with subjects in each age group receiving the same four
      conditions. SUBJECTS: 24 elderly (mean age 65.2 years, 12 men and 12 women) and
      24 young (mean age 21.8 years, 12 men and 12 women) matched for handedness,
      gender, and education level. METHODS: SUBJECTS viewed a display that contained
      four light-gray squares arranged as if on the tips of a plus sign, then black X
      marks appeared and the subjects indicated whether one or two Xs appeared in the
      squares as quickly and accurately as possible. The time to respond and accuracy
      level were recorded. Two types of displays were used; one with squares spread out
      over a large area and one with squares condensed into a small area. In two thirds
      of the trials the size remained the same (with half being large, and half small),
      and in one third it changed (with half of these trials changing from large-to
      small and half from small-to-large). RESULTS: In the trials that had a consistent
      display size, the elderly subjects performed the task better with the smaller
      display, whereas the young subjects performed equally well with both sized
      displays. In addition, the elderly found it easier to shift from large to small
      scope than to maintain attention at the large scope; in contrast, the younger
      subjects found it easiest to maintain attention on a static display size.
      CONCLUSIONS: The elderly prefer to focus attention on a smaller region of space
      than do younger people.

PMID- 9933734
TI  - Relationship between oral alveolar bone loss and aging among African-American and
      Caucasian individuals.
AB  - BACKGROUND: The periodontal attachment apparatus consists of the periodontal
      ligament, alveolar bone, cementum and supra-crestal connective tissue. They are
      interdependent and provide protection and support to the dentition. It is
      theorized that the integrity of the periodontal apparatus can be maintained
      throughout life by exercising comprehensive oral hygiene practices and routine
      dental care. Additionally, it appears to be unaffected by aging. As a
      consequence, the investigators performed a study to determine the effects of
      chronological aging on alveolar bone loss. OBJECTIVE: The present study was
      conducted to determine the relationship between oral alveolar bone loss, oral
      hygiene, and aging among African-American and Caucasian populations. METHODS: The
      population consisted of 229 individuals. There were 131 men and 98 women. With
      respect to race there were 89 African-Americans and 140 Caucasians. Oral
      examinations, oral hygiene and missing teeth determinations and bitewing
      radiographs were performed on all the individuals. Radiographs were digitized and
      measurements were made from the cementum/enamel junction to the alveolar bone
      crest. Measurements were made for both the maxillary and mandibular jaws.
      RESULTS: The results of the study showed a significant multiple linear regression
      model relationship between oral bone loss and aging. Oral hygiene was a factor,
      but contributed only slightly to the overall model. Race, gender and the number
      of missing teeth were not significant variables in the overall model. CONCLUSION:
      The results of this study suggest age-related alveolar bone loss.

PMID- 9933735
TI  - Murmurs associated with mitral annular calcification and aortic sclerosis.
AB  - BACKGROUND: Auscultation of patients with mitral annular calcification on
      echocardiography revealed a particular constellation of findings. OBJECTIVE: To
      test the hypothesis that a particular auscultatory constellation provides a high
      degree of certainty in diagnosing the combination of mitral annular calcification
      and aortic sclerosis so often found in the elderly. METHODS: Two groups of
      patients were studied to evaluate the particular auscultatory constellation under
      consideration which consisted of: (1) a harsh ejection systolic murmur heard from
      the 2nd right interspace to the cardiac apex and usually loudest between the 3rd
      left interspace and the apex; (2) the murmur radiates from the apex towards the
      left axilla and radiates poorly or not at all from the 2nd right interspace to
      the neck, and (3) the 2nd heart sound at the cardiac base is normal in intensity,
      and no ejection clicks are present. Group 1 consisted of patients with mitral
      annular calcification on echocardiographic examination, and group 2 consisted of
      patients in whom the particular constellation of auscultatory findings was
      present and who were then referred for echocardiographic assessment. RESULTS: The
      particular auscultatory constellation under investigation allowed the diagnosis
      of the presence of the combination of mitral annular calcification and aortic
      sclerosis with substantial accuracy. CONCLUSION: The findings in this exploratory
      study suggest that the pathologic combination of mitral annular calcification and
      aortic sclerosis can be diagnosed with a reasonably high degree of certainty in
      elderly patients, if the particular auscultatory configuration is identified.

PMID- 9933736
TI  - Water-insoluble camptothecin analogues as potential antiviral drugs.
AB  - In addition to being causative agents of infectious diseases in animals and
      humans, DNA viruses have served as models for the study of eukaryotic molecular
      mechanisms including replication and transcription. Studies of DNA virus
      functions utilizing cell-free systems and virus-infected cells in culture, in the
      presence of the anticancer drug camptothecin (CPT), have demonstrated that CPT is
      a potent inhibitor of replication, transcription and packaging of double-stranded
      DNA-containing adenoviruses, papovaviruses and herpesviruses, and the single-
      stranded DNA-containing autonomous parvoviruses. CPT inhibits viral functions by
      inhibiting topoisomer- ase I, a host cell enzyme required for initiation and
      completion of the viral functions. These findings indicate that CPT analogues
      could be developed for use as potent drugs against DNA viruses.

PMID- 9933737
TI  - Heterologous gene expression in avian cells: potential as a producer of
      recombinant proteins.
AB  - We have explored the possibility of using avian cells for the expression of human
      proteins. We found that various avian cells including quail fibrosarcoma cells
      (QF), duck embryo cells (DE) and primary chicken embryo fibroblasts (CE) could
      efficiently be transfected with DNA by calcium phosphate coprecipitation, and
      that promoters which are transcriptionally active in mammalian cells also
      functioned well in these avian cells. Among the promoters we tested, the major
      immediate early promoter of human cytomegalovirus drove the highest level of
      chloramphenicol acetyl transferase (CAT) expression, outperforming the SV40 early
      promoter and the RSV LTR. Using the bacterial CAT gene as a reporter, we found
      that levels of CAT activity were higher in QF and DE cells than in mammalian
      cells such as CHO, HeLa, Vero and 293T cells. We further cloned a sequence
      encoding human erythropoietin (EPO) and compared its expression in QF and
      mammalian cells. Consistent with the CAT data, in transient transfection assays,
      QF cells produced higher levels of EPO than the mammalian cell lines tested. QF
      cells which can be passaged permanently were stably transfected with an EPO
      expression vector. The subcloned QF line was able to produce up to 1,700 U/ml EPO
      from 3 x 10(6) cells in 72 h. Purified QF-produced EPO showed a broad but
      discrete protein band, ranging from 33 to 41 kD and was as biologically active as
      CHO-produced EPO. Although a number of factors still remain to be optimized, our
      results demonstrate the potential of avian cells such as QF as producers of
      heterologous proteins.

PMID- 9933738
TI  - A PstI polymorphism detects the mutation of serine128 to arginine in CD 62E gene 
      a risk factor for coronary artery disease.
AB  - The mutation of serine128 to arginine in the CD 62E gene is a risk factor for
      coronary artery disease (CAD). We designed a new method to detect this mutation
      based on the observation that it is due to a transversion of nucleotide A561 to
      C, which abolishes a PstI recognition site. Two alleles, A and C, are easily
      typed when genomic DNA is amplified by PCR, digested with PstI, and separated on
      agarose gels. Among 153 people who underwent an elective, diagnostic
      arteriography in Johns Hopkins Hospital, we found that the C allele accounts for
      19.5% in angiographically documented CAD patients (n = 82). It is significantly
      higher than the 10.6% frequency observed in normal controls (n = 71, p < 0.05).
      It indicates that the C allele is associated with early-onset CAD. This new
      method should facilitate the screening of this mutant allele in large populations
      and contribute to the understanding of the molecular mechanism underlying the
      association of this mutation with CAD.

PMID- 9933739
TI  - Acute exercise enhances receptor-mediated endothelium-dependent vasodilation by
      receptor upregulation.
AB  - The effects of acute exercise on receptor-mediated endothelium-dependent
      vasodilation and its possible mechanisms were investigated in the presence of
      indomethacin. Male Wistar rats (16-20 weeks old) were divided into control and
      exercise groups. The exercise group ran on a drum exerciser until exhaustion,
      followed by immediate decapitation. Acetylcholine (ACh)- or clonidine (CLO)
      induced vasodilating responses in thoracic aortae of the control and exercise
      groups were compared. Receptor-binding assays were performed to determine whether
      there were any upregulations of endothelial receptors after acute exercise. Our
      results indicated that acute exercise induced the following effects: (1) the dose
      response curves of ACh and CLO shifted to the left; (2) the high-affinity M3
      binding sites increased in number but not in affinity; (3) the alpha2 binding
      sites decreased in number but increased in affinity. We conclude that acute
      exercise enhances receptor-mediated vasodilation responses, at least in part, by
      regulating either endothelial receptor number or receptor affinity.

PMID- 9933740
TI  - Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines
      and inducible nitric oxide synthase expression and lung injury following
      endotoxin administration in rats.
AB  - Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to
      vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor,
      NG-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing
      acute lung injury. In the present study, we evaluated the effects of NOS blockade
      by different mechanisms on the endotoxin-induced changes. In anesthetized rats,
      lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in
      a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an
      eightfold increase of exhaled NO during an observation period of 4 h. After the
      experiment, the lung weight was obtained and lung tissues were taken for the
      determination of mRNA expressions of inducible NOS (iNOS), interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha-(TNF-alpha). Histological examination of
      the lungs was also performed. In the control group injected with saline solution,
      mRNA expressions of iNOS, IL-1beta and TNF-alpha were absent. Four hours after
      LPS, the mRNA expressions of iNOS and IL-1beta were still significantly enhanced,
      but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase
      in lung weight. Pathological examination revealed endothelial damage and
      interstitial edema. Various NOS inhibitors were given 1 h after LPS
      administration. These agents included Nomega-nitro-L-arginine methyl ester (L
      NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S, S'-1,4-phenylene-bis
      (1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a
      relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of
      iNOS expression. These NOS inhibitors all effectively reversed the systemic
      hypotension, reduced the exhaled NO concentration and prevented acute lung
      injury. The LPS-induced mRNA expressions of iNOS and IL-1beta were also
      significantly depressed by these NOS inhibitors. Our results suggest that NO
      production through the iNOS pathway is responsible for endotoxin-induced lung
      injury. Certain cytokines such as IL-1beta are possibly involved. These changes
      are minimized by NOS inhibitors through different mechanisms.

PMID- 9933741
TI  - Effect of excitatory amino acid neurotransmitters on acid secretion in the rat
      stomach.
AB  - Excitatory amino acids (EAAs), in particular, L-aspartate (L-Asp) neurons and
      their processes, were localized in the rat stomach using a immunohistochemical
      method with specific antibodies against either L-Asp or its synthesizing enzyme,
      aspartate aminotransferase (AAT). Myenteric ganglia and nerve bundles in the
      circular muscle and in the longitudinal muscle were found to be AAT- or L-Asp
      positive. In addition, AAT- or L-Asp-positive cells were also found in the muscle
      layer and the deep mucosal layer. The distribution of AAT- or L-Asp-positive
      cells in both the mucosal and muscle layers was heterogeneous in the stomach. In
      addition, L-Asp at 10(-6) M negligibly influenced acid secretion in an everted
      preparation of isolated rat stomach. However, according to our results, L-Asp
      markedly inhibited the histamine-stimulated acid secretion, but not the
      oxotremorine- or the pentagastrin-stimulated acid secretion. Furthermore, L-Asp
      also inhibited histamine-induced elevation of cAMP. L- Asp itself did not affect
      the cAMP level although it elevated the cGMP level in the stomach. Moreover,
      either (+)2-amino-5-phosphonovaleric acid or (+/-)3-(2-carboxypiperazin-4
      yl)prophyl-1-phosphonic acid, i.e. two specific antagonists for N-methyl-D
      aspartic acid (NMDA) receptors, blocked the inhibitory effect of L-Asp on
      histamine-stimulated acid secretion or histamine-induced elevation of cAMP. Since
      cAMP has been strongly implicated as the second messenger involved in histamine
      induced acid secretion, we believe that L-Asp regulates acid secretion in the
      stomach by inhibiting histamine release through the NMDA receptors, subsequently
      lowering the level of cAMP and ultimately reducing acid secretion.

PMID- 9933742
TI  - Activation of a cryptic splice donor in human immunodeficiency virus type-1.
AB  - The human immunodeficiency virus type-1 regulatory protein Rev is absolutely
      required for the production of viral structural proteins. Splice sites have been
      seen to function as cis-acting repressor sequendes (CRS) and inhibit expression
      of the Rev-dependent RNAs. In order to analyze the role of a splice donor in Rev
      dependence, the wild-type 5' splice donor of HIV-1 was mutated in the context of
      other gag sequences. Following transient transfection, RNA expression by RT-PCR
      was analyzed. The unspliced RNA produced by the mutant construct still required
      Rev for the cytoplasmic accumulation of the RNA. Despite deletion of the wild
      type 5' splice donor and the tat splice acceptor was used. A cryptic splice donor
      was identified by PCR and subsequent cloning of the spliced RNA. The cryptic site
      is 5/9 to the consensus sequence and located immediately downstream of the
      initiation codon (ATG) for Gag. Analysis of the RNA product containing the
      cryptic splice donor revealed that the Rev was required for the cytoplasmic
      accumulation of unspliced RNA, while spliced RNA was Rev independent.
      Transfection of a wild-type construct also demonstrated usage of the cryptic
      splice donor. These results indicate that a cryptic splice donor can be activated
      when the wild-type splice donor is inactivated and that the cryptic splice donor
      may retain Rev regulation. The findings also suggest the potential for cryptic
      splice sites to serve as CRS in the determining the Rev dependence of viral RNAs.

PMID- 9933743
TI  - Peptide loading in the endoplasmic reticulum accelerates trafficking of
      peptide:MHC class II complexes in B cells.
AB  - In a combination of biochemical and immunoelectron-microscopical approaches we
      studied intracellular trafficking and localization of the endoplasmic-reticulum
      (ER)-formed complexes of murine MHC class II molecule I-Ab and an antigenic
      peptide Ealpha52-68 covalently linked to its beta-chain. The association with the
      peptide in the ER leads to sharp acceleration of the intracellular trafficking of
      the complexes to the plasma membrane. Within the cells, Ealpha52-68:I-Ab
      complexes accumulate in the multivesicular MHC class II compartment (MIIC), but
      not in denser multilaminar or intermediate type MIICs. The changes in the
      trafficking of ER-formed complexes result solely from the presence of the
      tethered peptide, since wild-type class II molecules traffic similarly in bare
      lymphocyte syndrome cells and in wild-type antigen-presenting cells.

PMID- 9933745
TI  - Pathophysiology of peritoneal fluid eosinophilia in peritoneal dialysis patients.

PMID- 9933744
TI  - Expression of foreign antigens on the surface of Escherichia coli by fusion to
      the outer membrane protein traT.
AB  - The traT gene is one of the F factor transfer genes and encodes an outer membrane
      protein which is involved in interactions between an Escherichia coli and its
      surroundings. This protein was altered so as to permit the expression of foreign
      proteins on the outer membrane of E. coli in this study. A 729-bp DNA fragment,
      including the leader and entire structural gene sequence of traT, was amplified
      and obtained by PCR. This sequence was then subcloned downstream of the tac
      promoter of pDR540, resulting in a TraT expression vector, pT2. Here, we report
      that the expression of TraT protein, fused either with a partial pre-S antigen of
      hepatitis B virus (60 and 98 amino acids, respectively) or with the snake venom
      rhodostomin (72 amino acids), was successfully achieved on the outer membrane of
      E. coli, using the pT2 plasmid. This result was demonstrated using dot blot and
      immunofluorescence analysis. This finding supports the notion that the pT2
      plasmid can be used as an E. coli display system. This system can detect a
      foreign peptide of about 100 amino acid residues in length on the bacterial
      surface.

PMID- 9933746
TI  - Distinguished Scientists Lecture Series. New developments in kidney development.
AB  - BACKGROUND/AIMS: The number of kidney transplantations performed per year is
      limited due to the availability of donor organs. One possible solution to the
      organ shortage is the use of renal xenografts. However, the transplantation of
      xenografts is complicated by rejection. METHODS: It has been postulated that the
      host immune response might be attenuated following the transplantation of
      embryonic kidneys (metanephroi) rather than developed (adult kidneys).
      Transplanted metanephroi become chimeric organs in that their blood supply
      originates from the host. It is possible to transplant a developing metanephros,
      without the use of immunosuppression, from one outbred rat to another. RESULTS:
      Transplanted metanephroi grow, develop, become vascularized, and function in host
      rats. In contrast, developed adult kidneys transplanted from one rat to another
      undergo rejection within 7 days after transplantation. CONCLUSIONS: These
      observations suggest that metanephric tissue may be less immunogenic than adult
      kidney. Transplantation of metanephroi represents a new development that could
      lead to a novel therapeutic approach to the treatment of chronic renal failure.

PMID- 9933747
TI  - Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less
      precise than measured and predicted creatinine clearance.
AB  - The work was devised to compare measurements of glomerular filtration rate (GFR)
      by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to
      those by creatinine clearance (measured and predicted by Cockroft and Gault) and
      by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy
      controls and 50 patients with renal disease. Compared to inulin clearance used as
      the gold standard, 99mTc-DTPA overestimated at low and underestimated at high
      GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except
      for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had
      the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance
      the lowest. In correlation analyses, 81.5% of the interindividual variability for
      measured creatinine clearance could be explained by true differences in inulin
      clearance; this value dropped to 59.1 and 57.4% for predicted creatinine
      clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73
      m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the
      inulin measurement. It can be inferred that 99mTc-DTPA clearance from the
      renogram is less precise than measured and predicted creatinine clearance.

PMID- 9933748
TI  - Isolation of a coronavirus from kidney biopsies of endemic Balkan nephropathy
      patients.
AB  - Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited
      to Bulgaria, Rumania and former Yugoslavia. Primary kidney tissue cultures were
      established as explants from tissue obtained at operations from 5 EBN patients
      with urinary tract tumors. Four out of the five biopsy specimens on extended
      culture incubation at 33 degrees C yielded a coronavirus virus (EBNV) which was
      cytopathogenic for human fibroblast and Vero cells. In cells inoculated with
      EBNV, cytoplasmic immunofluorescence was found using antisera for human
      coronaviruses OC43 and 229E as well as the porcine transmissible gastroenteric
      virus and avian (chicken) bronchitis virus. In neutralization tests, EBNV failed
      to react with antisera to these viruses. Using hyperimmune serum raised with
      EBNV, positive cytoplasmic immunofluorescence was seen with cells infected with
      OC43, 229E, TGV and significantly with the kidney tissue of the biopsy specimens
      from the EBN patients. A screen for neutralizing antibody using the EBN virus
      revealed that 87.2% of EBN patients on dialysis were positive, also 74% of people
      from an endemic area were also positive, while only 13.5% from outside were
      positive. It is suggested that a coronavirus is involved in the etiology of the
      disease and that humans are an incidental host of a coronavirus zoonosis.

PMID- 9933749
TI  - Hemodialysis-related nodulocystic acne treated with isotretinoin.
AB  - Some hemodialysis patients, without taking any acnegenic agents, developed severe
      nodulocystic acne with unknown causes. Because nodulocystic acne poorly responds
      to conventional acne therapy and increases the black pigmentation in the face, it
      severely interferes with the quality of life of these patients. To investigate
      whether isotretinoin is effective in treating hemodialysis patients with severe
      nodulocystic acne, we undertook a prospective, randomized, single-blind study. A
      total of 20 patients with nodulocystic acne participated in the study, of whom 18
      completed it. Ten patients received isotretinoin 10 mg/day (5 mg/capsule) for 3
      months as a study group and the other 10 took placebo for 3 months as a control
      group. The severity of acne and treatment-related side effects were evaluated
      monthly by a questionnaire and laboratory evaluation which included liver
      function tests, blood lipids and blood platelet counts. The results showed
      isotretinoin treatment significantly reduced the severity of acne of the study
      group patients after 1 month (scales of acne severity: 4.0 +/- 0.0 vs. 3.13 +/-
      0.35, p < 0. 01) and 3 months (4.0 +/- 0.0 vs. 1.5 +/- 0.76, p < 0.01) of follow
      up. In addition, the severity of acne of the study group patients was
      significantly less than that of the control group patients after 1 month (3.13 +/
      0.35 vs. 3.80 +/- 0.42, p < 0.01) and 3 months (1.5 +/- 0.76 vs. 3.70 +/- 0.48,
      p < 0.001) of treatment. Only mild side effects were noted. No significant
      changes of biochemical evaluation were found except that a mild elevation of
      aspartate aminotransferase was noted in the study group patients. However, two
      study group patients withdrew from the trial because of isotretinoin-related side
      effects and toxic hepatitis. In summary, our study first demonstrated that the
      small dose of isotretinoin effectively treated nodulocystic acne of hemodialysis
      patients and the side effects were mild. This result suggests that isotretinoin
      may be the treatment of choice for nodulocystic acne in end-stage renal disease
      patients with renal replacement therapy. The liver function and other
      isotretinoin-related side effects in these patients should be carefully
      monitored.

PMID- 9933750
TI  - Effects of oral supplementation with evening primrose oil for six weeks on plasma
      essential fatty acids and uremic skin symptoms in hemodialysis patients.
AB  - Abnormalities in plasma composition of essential fatty acids (EFAs) may be
      associated with the etiology of pruritus and other skin problems in patients
      undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n
      6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7
      dialysis patients were randomly assigned to receive either gamma-linolenic acid
      (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6
      weeks. Plasma concentrations of EFA were analyzed by gas chromatography and
      uremic skin symptoms were assessed for dryness, pruritus and erythema by
      questionnaire and visual inspection in a double-blind manner. The patients given
      EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic
      acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant
      change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin
      E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p <
      0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a
      significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients
      given EPO showed a significant (p < 0.05) improvement in the skin scores for the
      three different uremic skin symptoms over the baseline values and a trend toward
      a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA.
      Results indicate that GLA-rich EPO would be a more favorable supplemental source
      than LA in terms of shifting eicosanoid metabolism toward a less inflammation
      status through modifying plasma concentrations of their precursor n-6 EFAs.
      Further studies are required to confirm the efficacy and safety of EPO therapy
      for the treatment of uremic pruritus.

PMID- 9933751
TI  - Plasma and urine levels of uroguanylin, a new natriuretic peptide, in nephrotic
      syndrome.
AB  - Uroguanylin, a new natriuretic peptide originally isolated from urine, stimulates
      the membrane guanylate cyclase C receptor. No information, however, is available
      on the plasma and urine levels of uroguanylin in nephrotic syndrome (NS), the
      state associated with sodium and water retention. Using a sensitive
      radioimmunoassay, we measured the plasma and urine concentrations of
      immunoreactive (ir-)uroguanylin in NS patients and compared them with those of
      patients with non-nephrotic glomerulonephritis. Plasma ir-uroguanylin, blood
      pressure and the cardiothoracic ratio were higher, and urine excretion of ir
      uroguanylin was lower in the NS patients. Plasma ir-uroguanylin in the NS
      patients significantly decreased during remission as compared with findings on
      admission. There was a significant inverse correlation between the concentration
      of plasma ir-uroguanylin and that of serum total protein or albumin. Moreover,
      fluid retention in the NS patients was correlated with the changes in plasma ir
      uroguanylin between admission and remission, indicative that the plasma
      concentration increases with the severity of the nephrotic state. Taking into
      account its potent natriuretic effect, these findings suggest that uroguanylin
      may function in the pathophysiological mechanism in NS.

PMID- 9933752
TI  - Association between HLA-DRB1*15 and Japanese patients with rheumatoid arthritis
      complicated by renal involvement.
AB  - We performed serological phenotyping of HLA antigens in 175 patients with
      rheumatoid arthritis (RA) with (n = 41) and without (n = 134) renal involvement
      (RI), and DNA typing of HLA class II alleles in 75 patients. Among the patients
      with RA, the frequency of serologically determined HLA-DR4 was found to be
      significantly increased (odds ratio: 1.8, confidence interval: 1.3-2.5, p =
      2.4x10(-4)). In the patients without RI, the frequency of serological DR4
      significantly increased (odds ratio: 2.2, confidence interval: 1.6-3.3, p = 2.
      6x10(-5)). On the other hand, among the patients with RI, a serological
      determinant, DR15, did significantly increase (odds ratio: 2.7, confidence
      interval: 0.9-8.4, p = 1.2x10(-3)) in comparison to the controls. At the DNA
      level, we found that the association of Japanese RA patients with serological HLA
      DR4 was based on that with a genotype of HLA-DRB1*0405 (odds ratio: 2.4,
      confidence interval: 1.5-4.0, p = 4.4x10(-4)) and also found an association of
      HLA-DRB1*1501 (odds ratio: 2.8, confidence interval: 1.2-6.6, p = 0.017) with RA
      patients having RI. Our results confirmed the association of HLA-DRB1*04 with RA
      over the ethnic barrier at the DNA level. Our results also suggested a distinct
      genetic effect of HLA-DRB1*1501 in the aspect of the susceptibility of RI in RA.

PMID- 9933753
TI  - Adrenergic blockade in diabetic and uninephrectomized rats: effects on renal size
      and on renal and urinary contents of epidermal growth factor.
AB  - The present study reports on the effects of adrenergic blocking agents on the
      renal growth and on the renal content and urinary excretion of epidermal growth
      factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats.
      Diabetic and uninephrectomized rats were allocated to groups treated with either
      saline or adrenergic antagonists and compared to controls and sham-operated
      controls, respectively. 24-hour urine samples were obtained on days 7, 14, and 21
      and renal tissue samples on day 21. The 24-hour urinary excretion of EGF from
      controls and saline-treated diabetic rats was comparable. In adrenergic
      antagonist treated diabetic rats, it was reduced by at least 40% throughout the
      study period. Uninephrectomy caused a 50% reduction in the urinary excretion of
      EGF. This was not influenced by treatment with an adrenergic antagonist. After 3
      weeks, saline-treated diabetic rats had an increase of 33% in kidney weight when
      compared to controls. The adrenergic antagonist treated diabetic groups had a
      significantly lower increase of 15%. Postnephrectomized renal growth was not
      affected by adrenergic antagonists. The total renal content of EGF was comparable
      in the saline-treated diabetic group and the control group, but was reduced by
      approximately 50% in the kidneys from the adrenergic antagonist treated diabetic
      groups. Renal EGF mRNA levels were also reduced in adrenergic antagonist treated
      diabetic rats. In contrast to diabetes, the renal growth following nephrectomy
      was not affected by adrenergic blocking agents. These results provide evidence
      for fundamental differences between diabetes-related renal growth and that
      observed in compensation to nephrectomy and suggest a connection between
      adrenergic activity, renal growth, and EGF in diabetes.

PMID- 9933754
TI  - Regression of glomerular injury by kallikrein infusion in Dahl salt-sensitive
      rats is a bradykinin B2-receptor-mediated event.
AB  - AIMS: We investigated whether kallikrein infusion attenuates renal injury in Dahl
      salt-sensitive rats with hypertension and assessed the role of bradykinin-nitric
      oxide axis in the renal protection using HOE-140, the bradykinin type-2 (B2)
      receptor specific antagonist. METHODS: Subdepressor dose of purified rat urinary
      kallikrein (RUK) (400 ng/day) was continuously infused through the jugular vein
      by an osmotic mini-pump for 4 weeks in Dahl salt-sensitive (Dahl S) rats fed a
      high-salt (2% NaCl) diet. RESULTS: Blood pressure increased in a time-dependent
      manner in Dahl S rats fed a high-salt diet. The RUK infusion did not influence
      the elevation of blood pressure in Dahl S rats. However, the RUK infusion
      significantly decreased urinary protein excretion, and increased glomerular
      filtration rate, as compared with untreated high-salt Dahl S rats. Morphological
      investigation disclosed that the RUK infusion significantly attenuated
      glomerulosclerosis and arterial and tubular injuries in the kidney of
      hypertensive Dahl S rats. The RUK infusion produced an increase in urinary
      excretions of nitric oxide and cyclic guanosine monophosphate. In addition, the
      RUK infusion enhanced the generation of nitric oxide from the kidney slices. The
      functional and morphological effects of the RUK infusion on the kidney were
      completely lessened by co-administration of the bradykinin B2-receptor
      antagonist, HOE-140. CONCLUSION: Long-term infusion of subdepressor dose of rat
      urinary kallikrein attenuates functionally and morphologically the progression of
      renal injury in Dahl rats susceptible to salt-induced hypertension, and that the
      protection is mediated by stimulation of bradykinin B2 receptor.

PMID- 9933755
TI  - Effects of human alpha-1-acid glycoprotein on aminonucleoside-induced minimal
      change nephrosis in rats.
AB  - A minimal change nephrosis was induced in rats by a single intraperitoneal
      injection of puromycin aminonucleoside (100 mg/kg). This resulted in increased
      urine protein output, plasma creatinine, blood urine nitrogen, and relative
      kidney weight. Electronoptically, there was a retraction of the glomerular
      podocytic foot processes. When human alpha1-acid glycoprotein was injected at 600
      mg/kg intravenously on experimental days 6, 7, 8, and 9 into these animals, urine
      protein output decreased significantly, and the number of podocytic foot
      processes increased significantly. alpha1-Acid glycoprotein is rich in sialic
      acid and largely negatively charged. Its therapeutic role in nephrosis, which is
      characterized by a loss of sialic acid and a loss of negative charge, thereby
      leading to a loss of permselectivity, is discussed.

PMID- 9933756
TI  - Effect of ginsenoside-Rd in cephaloridine-induced renal disorder.
AB  - To determine whether ginsenoside-Rd ameliorates the renal injury induced by
      cephaloridine, the effect of cephaloridine was investigated in rats given
      ginsenoside-Rd preceding cephaloridine administration and in control rats given
      no ginsenoside-Rd. In control rats, blood, renal and urinary parameters and the
      activities of antioxidative enzymes in renal tissue deviated from the normal
      range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd
      was given orally for 30 consecutive days prior to cephaloridine injection, the
      activities of the antioxidation enzymes superoxide dismutase and catalase were
      higher, while malondialdehyde levels in serum and renal tissue were lower in the
      treated rats than in the controls. The urea nitrogen and creatinine levels in
      serum were decreased in rats given ginsenoside-Rd. Decreased urine volume,
      increased urinary osmotic pressure, and decreased urinary levels of glucose,
      protein, sodium and potassium demonstrated a protective action against the renal
      dysfunction caused by cephaloridine. In addition, it was demonstrated that
      ginsenoside-Rd affected cultured proximal tubule cells exposed to cephaloridine.

PMID- 9933757
TI  - Complement activation accelerates glomerular injury in diabetic rats.
AB  - A known inhibitor of the complement cascade (K-76 COONa) was administered to an
      inbred diabetic rat model to investigate whether the complement system may play a
      role in the progression of diabetic glomerulosclerosis. Drinking water containing
      K-76 COONa was available continuously to inbred diabetic rats (Otsuka Long-Evans
      Tokushima Fatty, OLETF) from the age of 25 to 55 weeks (Group L). Drinking water
      without K-76 COONa was similarly available to OLETF rats (Group H) and
      nondiabetic control rats (Long-Evans Tokushima Otsuka, LETO) (Group C). The
      levels of plasma glucose (mg/dl) at the 55th week were 156 +/- 16 in Group C, 252
      +/- 18 in Group L and 349 +/- 93 in Group H. There was no significant difference
      in the degree of diabetes between Group L and Group H. The levels of urinary
      protein at 55 weeks of age (mg/day) were 2.1 +/- 0.4 in Group C, 11. 6 +/- 1.5 in
      Group L and 18.0 +/- 2.8 in Group H. The level of urinary protein was
      significantly decreased by the administration of K-76 COONa. Histological
      examination of renal specimens from the sacrificed rats at 55 weeks of age
      revealed diffuse mesangial expansion in almost all glomeruli in Group H,
      exudative lesions in 30% of glomeruli in Group H, and only mild mesangial
      expansion was recognized in Group L. Immunofluorescence study revealed brilliant
      staining of C3 and immunoglobulins (Ig) in Group H; trace staining of Ig and no
      staining of C3 were recognized in Group L. The incubation study with guinea pig
      serum and glomeruli from rats revealed that Ig and complement components also
      bound to injured glomeruli in vitro. These data indicate that the complement
      cascade is activated by injured glomeruli and this activation exacerbates
      diabetic glomerulosclerosis.

PMID- 9933758
TI  - Effect of a novel immunosuppressant, FK 506, on autoimmune glomerulonephritis in
      Brown Norway rats.
AB  - Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune
      glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant
      FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were
      treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/
      week). Rats developed proteinuria at day 7, which reached a plateau level at day
      14. On day 14, renal histology showed prominent mesangial cellular proliferation
      and the expansion of mesangial matrix. Electron microscopic study showed the
      effacement of visceral epithelial foot processes and the microvillous
      transformation of the visceral epithelium. Immunofluorescence study showed a
      strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli.
      Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of
      proteinuria at day 14 (621.4 +/- 30.5 vs. 2.2 +/- 2.7 mg/day) and the
      morphological lesions. These findings suggest that FK 506 could be useful for the
      therapy of certain types of human glomerulonephritis.

PMID- 9933761
TI  - Hydrogen peroxide induces necrosis, apoptosis, oncosis and apoptotic oncosis of
      mouse terminal proximal straight tubule cells.
AB  - Hydrogen peroxide (H2O2) has been shown to be an important mediator of ischemic
      and toxic tubular damage. The purpose of this study was to identify the mode of
      cell death observed in H2O2-exposed cultures of mouse terminal proximal straight
      tubule (S3) cells. H2O2 induced a dose- and time-dependent decrease in viability
      of S3 cells. Morphologically, S3 cells exposed to H2O2 (0.05-0.1 mM) showed
      features of necrosis, apoptosis, oncosis and apoptotic oncosis, whereas necrosis
      occurred most frequently in every experimental condition tested. On the other
      hand, agarose gel electrophoresis of DNA extracted from S3 cells exposed to H2O2
      revealed a typical DNA ladder pattern. These data suggest that H2O2-induced
      proximal tubule damages are associated with the induction of various modes of
      cell death including necrosis, apoptosis, oncosis and apoptotic oncosis, and with
      the activation of endonuclease.

PMID- 9933760
TI  - Activation of epidermal growth factor receptor in the early phase after renal
      ischemia-reperfusion in rat.
AB  - In order to estimate a regenerative response in the early phase after renal
      ischemia-reperfusion in rat, we examined the time course of the activation of
      epidermal growth factor receptor (EGFR) as a response of signal transduction
      pathway after 45 min ischemia in kidney. The activation of EGFR was observed 5-30
      min after the start of reperfusion. Simultaneously, superoxide anion/hydrogen
      peroxide generated in the mitochondrial fraction was elevated during the same
      period. On the other hand, the level of EGF decreased in a time-dependent manner.
      These results suggested that superoxide anion/hydrogen peroxide generated during
      the ischemia-reperfusion other than EGF could act as an activator for the EGFR.
      In summary, the activation of EGFR is important as a regenerative response at an
      early stage after the start of reperfusion in ischemic kidney.

PMID- 9933762
TI  - Cyclophosphamide-associated carcinoma of the urinary bladder in Behcet's disease.

PMID- 9933759
TI  - Renoprotective effects of captopril in hypertension induced by nitric oxide
      synthase inhibition in experimental nephritis.
AB  - OBJECTIVE: To investigate effects of angiotensin I converting enzyme (ACE)
      inhibition in experimental nephritis during chronic inhibition of nitric oxide
      (NO) synthase. METHODS: Rats with and without autoimmune Heymann nephritis were
      treated with a NO synthase inhibitor L-NAME (50 mg/100 ml) and/or an ACE
      inhibitor captopril (20 mg/100 ml) in drinking water for 12 weeks. Urinary cGMP
      excretion was used as an indirect measure of NO activity. Blood pressure, urinary
      albumin, nitrite and nitrate levels, plasma ANP, and plasma renin activity were
      measured. Kidneys were examined with light microscopy and immunohistochemical
      methods. RESULTS: Captopril treatment protected rats receiving L-NAME and none of
      the captopril-treated rats died. Mortality was greatest in the nephritis-L-NAME
      (57%) and L-NAME (43%) groups. Captopril normalized cGMP excretion, blood
      pressure, and prevented partly the appearance of albuminuria. Peritubular
      infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME
      group (found in 80% of the rats) as compared with the nephritis (20%), L-NAME
      (40%), and control (0%) groups. The peritubular cell infiltration caused by L
      NAME was prevented by captopril treatment. L-NAME-induced hypertension was
      associated with cardiac hypertrophy and this was prevented by captopril.
      CONCLUSIONS: NO may play an important renoprotective role in disease progression
      of chronic membranous glomerulonephritis. Captopril prevents L-NAME-induced
      hypertension, improves survival, and ameliorates renal damage in this type of
      nephritis. Dysfunction of renal NO pathways may be an important factor causing
      progressive renal damage in chronic nephritis. Our results suggest that the
      dysfunctional renal NO system may be beneficially activated by ACE inhibitors.

PMID- 9933763
TI  - Effect of ciclosporin on triglyceridemia in long-term renal transplant
      recipients.

PMID- 9933764
TI  - Cortical nephrocalcinosis induced by extracorporeal shock wave lithotripsy.

PMID- 9933765
TI  - HCV Infection:'Six years after' in a dialysis unit.

PMID- 9933766
TI  - Hemophagocytic syndrome in a patient with Hashimoto's thyroiditis and membranous
      nephritis.

PMID- 9933767
TI  - Lack of efficacy of early plasma exchange in renal toxicity from Cortinarius
      orellanus.

PMID- 9933768
TI  - Cataract epidemiology performed with Scheimpflug documentation.
AB  - Cataract epidemiological surveys applying a photodocumentation system were
      performed by the author's group in three climatically different sites with
      racially different populations: Noto (Japan), Reykjavik (Iceland) and Singapore.
      Data regarding age- and sex-related changes in lens transparency decrease,
      prevalence and type of opacification are specific for the three populations
      studied. Direct comparisons of the three different populations revealed that the
      age-related prevalence of lens opacification, including whole grades, in the
      Japanese and Icelandic populations was almost the same, whereas that of the
      Singaporeans was significantly higher. However, the percentage of progressed
      cases was highest among Singaporeans, followed by the Japanese and Icelanders.
      Although the application of photodocumentation for cataract epidemiological
      studies has been limited up to now mainly because of high cost and sophisticated
      and time-consuming examination methods, more accurate, reliable and objective
      data can be obtained which will allow prospective decisions on the incidence of
      cataract.

PMID- 9933769
TI  - Epidemiology of cataract in India: combating plans and strategies.
AB  - Blindness due to cataract presents an enormous problem in India not only in terms
      of human morbidity but also in terms of economic loss and social burden. The
      WHO/NPCB (National Programme for Control of Blindness) survey has shown that
      there is a backlog of over 22 million blind eyes (12 million blind people) in
      India, and 80.1% of these are blind due to cataract. The annual incidence of
      cataract blindness is about 3.8 million. The present annual level of performance
      is in the order of about 1.6-1.9 million cataract operations. To clear the
      backlog of cataract cases by the year 2000 and to tackle the rising incidence, 5
      6 million cataract operations annually will have to be performed as against the
      present rate of 1. 7 million per year. India is undertaking a new long-term
      initiative to expand the capability of cataract surgery and service levels with
      financial assistance from the World Bank. An important feature of this initiative
      is the attention given to spread the cataract blindness programme in rural and
      tribal areas. The second feature is the emphasis placed on modern extracapsular
      cataract extraction with intra-ocular lens implantation as the preferred surgical
      technique. Another noteworthy feature is developing institutional capacity and
      appropriate co-ordination mechanisms for collaboration between the non-government
      organization and the public sector to expand coverage to the most disadvantaged
      populations. The fourth and the most important strategy is to carry out intensive
      campaigns at the state and national levels against cataract blindness in order to
      substantially increase the demand for cataract services. A country like India has
      more significance for such a plan in view of the fact that various social,
      economic and environmental factors contribute to cataract blindness in
      populations at a much younger age.

PMID- 9933770
TI  - An index for human lens transparency related to age and lens layer: comparison
      between normal volunteers and diabetic patients with still clear lenses.
AB  - OBJECTIVE: The light scattering intensity of normal, clear lenses varies with age
      and with the localization within the lens. Realizing the biometry of single lens
      areas together with their relevant light scattering intensity one should be able
      to calculate an index to express the lens transparency properties of normal human
      lenses in dependence on age. Performing the same procedure in cases of diabetic
      patients with still clear lenses it should become possible to obtain an index for
      the lens transparency properties of lenses under the 'risk factor' diabetes.
      METHODS: 748 eyes with transparent lenses in 383 healthy individuals and 134 eyes
      with clear lenses in 70 subjects with diabetes were examined. Scheimpflug slit
      images of the lens were documented by a Nidek EAS-1000 instrument. Biometry for
      measuring the distance of the single lens layers from the anterior capsule and
      densitometry for determining the light scattering intensity of six defined lens
      layers along the (theoretical) optical axis were performed. The index of the lens
      transparency properties was calculated using the light scattering intensity of a
      defined lens layer and its distance from the anterior capsule. RESULTS: Lens
      thickness and light scattering intensities increased linearly with increasing age
      in the normal population as well as in the diabetic patients. The densitogram
      pattern of the light scattering intensities in the defined representative six
      points was similar in both populations, but in the diabetic group the lens
      thickness was larger and the light scattering intensities were higher at all
      ages. CONCLUSION: The index of lens transparency properties calculated with the
      light scattering intensities of a certain lens area and its distance from the
      anterior capsule is a useful measure of lens clarity in dependence on age.
      'Clear' lenses of the diabetic population show significantly higher indices for
      the lens transparency properties in all age groups.

PMID- 9933771
TI  - Light scattering in the human lens in childhood and adolescence.
AB  - The age-related increase in normal light scattering in the adult human lens has
      frequently been documented with Scheimpflug imaging techniques. There are only
      insufficient data on lens light scattering, however, from the first 2 decades of
      human life. After having obtained informed consent from their parents, the
      anterior eye segments of 26 children of both genders were documented with a
      Topcon SL-45 Scheimpflug camera on Kodak Tmax 400 ASA black-and-white film in 3
      meridians. The age of the children, who had either a normal visual acuity or best
      corrected visual acuity, ranged from 4 to 18 years. Thirty minutes prior to
      photography, maximal mydriasis was induced by 3-fold instillation of Mydriaticum
      Roche(R). Parallel to the Scheimpflug photographic documentation, all eyes were
      subjected to a basic ophthalmological examination. All images obtained were
      evaluated with microdensitometry as described earlier. The density data in young
      children demonstrate that there is very little light scattering in the central
      lens parts and only a faint zone of discontinuity apart from the 2 signals caused
      by the anterior and posterior capsules. Starting at the age of 14-15 years, the
      first separations occur in the zones of discontinuity, thus the first age
      correlated increase in light scattering. The data obtained demonstrate that the
      development of light scattering in the young lens differs from that in the adult
      lens. Our results point to the assumption that the development of protein light
      scattering in the lens correlates with physical life-time of the individual and
      not with the period of life in different species with various life expectancies.

PMID- 9933772
TI  - Variability in digital assessment of cortical and posterior subcapsular cataract.
AB  - To identify validity of the standardised Nidek EAS-1000 retroillumination image
      analysis, images of 450 consecutive patients were analysed for the standard 6.5
      mm and for the maximal pupil size. The software allows for separation of cortical
      and posterior subcapsular opacities and defines threshold for cataract
      automatically at 12% below the brightest point of the histogram of pixel
      luminescence. The results were compared with clinical Wilmer cataract grading.
      Correlation between clinical and digital assessment was 0.48* for cortical
      opacities in maximal pupil size, 0. 47* in 6.5 mm pupil size analyses, and 0.71*
      for posterior subcapsular opacities (*p < 0.001). In 24.6% of maximal pupil size
      analyses and in 11.7% of standard pupil size analyses standardisation revealed
      confounding features, such as other opacities of media, refractive shadows etc.,
      that masqueraded as cataract and interfered with the cortical opacity
      measurements. Automatic standardized analysis has reduced many sources of
      observer variation (level of illumination, pupil size and threshold adjustment),
      but the revealed range of confounding opacities and artifacts still requires
      observer interpretation.

PMID- 9933773
TI  - Comparison of clinical and digital assessment of nuclear optical density.
AB  - To compare the standardised Nidek EAS-1000 densitometric analysis of the lens
      with clinical assessment of the nucleus at an early stage of cataract
      development, 1,200 eyes of 1,204 participants of the VECAT study were assessed at
      the baseline using both subjective and objective lens grading. Standardisation of
      the automatic slit image analysis was achieved using a custom-designed EAS-1000
      Software version 3.01c. Among 6 measurements of nuclear optical density, the mean
      pixel luminescence of integrated anterior nuclear density correlated best with
      clinical assessment (R = 0.662, p < 0.001). Variance components that interfere
      with the assessment are defined.

PMID- 9933774
TI  - Postoperative lens position preoperatively determined by Scheimpflug photography.
AB  - The position of the artificial lens has an important influence on refractive
      power calculation. We compared the position of the crystalline lens with that of
      the artificial lens after cataract surgery by means of Scheimpflug photography. A
      difference in position of approximately 0.8 mm in the anterior direction could be
      determined.

PMID- 9933775
TI  - Image analysis of implanted rigid and foldable intraocular lenses in human eyes
      using Scheimpflug photography.
AB  - We evaluated the quality of imaging posterior chamber intraocular lenses (PC IOL)
      by Scheimpflug photography. We took photographs of 190 rigid or foldable PC IOLs
      using the Scheimpflug system EAS-1000 from Nidek and provided digital image
      analysis. We found a good imaging of PC IOLs and the cristalline lens capsule,
      data obtained by digital image analysis were reliable and reproducible and
      Scheimpflug photography could be demonstrated as a sensitive tool to show any
      irregularities of IOL material. Thus, we found in foldable IOLs 'glistenings',
      which did not have any influence on functional results and we could distinguish
      them from lens damage. We propose to use Scheimpflug tests regularly for the
      examination of implanted new types of IOLs.

PMID- 9933776
TI  - Scheimpflug records without distortion--a mythos?
AB  - The Scheimpflug principle was recommended as allowing distortion-free imaging;
      however, a detailed analysis reveals geometrical errors as well as distortions
      arising from absorption of light along the optical pathway. Correction formulas
      and factors will be presented and applied to the biometry of the eye.

PMID- 9933778
TI  - Abstracts 

PMID- 9933777
TI  - Animal study on the effects of catalin on aftercataract and posterior capsule
      opacification.
AB  - PURPOSE: To find out the role of Catalin in the prevention of posterior capsular
      opacification (PCO), we undertook this experimental study in rabbits. METHODS:
      Twenty rabbits (10 for the Catalin group and 10 for the placebo group) were
      operated on for extracapsular clear lens extraction in an aseptic environment. In
      all cases, capsulorrhexis of 8 mm diameter was carried out. Both the test drug
      and placebo were given at a dose of 4 times/day from the first postoperative day
      for 8 weeks. Common drugs in both groups were topical corticosteroid, antibiotic
      and cycloplegic drops. Periodic slitlamp examinations and photographic
      documentations were carried out to find any evidence of aftercataract. At the end
      ot 8 weeks, histopathological examination was carried out to document any
      evidence of aftercataract. RESULT: Overall, evidence of aftercataract was seen in
      6 rabbits in the control group and 3 in the Catalin group; the degree of PCO was
      higher in the placebo group. CONCLUSION: We found that Catalin played some role
      in preventing PCO.

PMID- 9933779
TI  - Consistency of tone-syllable alignment across different syllable structures and
      speaking rates.
AB  - Previous studies have reported that F0 contours of lexical tones in Mandarin are
      closely aligned with the syllables that carry them and that this alignment is
      late-adjusted so that the most appropriate F0 contour of a tone occurs mainly in
      the later portion of the host syllable. These studies, however, examined tone
      alignment only in syllables with a simple CV structure. The present study
      compared tone-syllable alignment patterns in syllables with a final nasal (the
      only final consonant allowed in Mandarin) to those without a final nasal at three
      speaking rates - normal, fast and slow. Experiment 1 found that regardless of
      internal syllable structure, the F0 contours for all of the four Mandarin tones
      maintain a consistent alignment to the syllables that carry them. Experiment 2
      found that whether or not the syllable has a final nasal and regardless of
      speaking rate, the F0 peak associated with the R (rising) tone always occurs near
      the offset of the R-tone-carrying syllable, the onset of the F0 rise always
      occurs near the center of the syllable and the slope of the rise does not vary
      systematically with either syllable structure or speaking rate. These findings
      are interpreted as indicating that the syllable is the proper domain for tone
      implementation and that tone contours such as rising and falling are probably
      implemented as integral dynamic targets rather than as sequences of static
      targets.

PMID- 9933780
TI  - The effect of speaking style on a locus equation characterization of stop place
      of articulation.
AB  - Locus equations were employed to assess the phonetic stability and
      distinctiveness of stop place categories in reduced speech. Twenty-two speakers
      produced stop consonant + vowel utterances in citation and spontaneous speech.
      Coarticulatory increases in hypoarticulated speech were documented only for /dV/
      and [gV] productions in front vowel contexts. Coarticulatory extents for /bV/ and
      [gV] in back vowel contexts remained stable across style changes. Discriminant
      analyses showed equivalent levels of correct classification across speaking
      styles. CV reduction was quantified by use of Euclidean distances separating stop
      place categories. Despite sensitivity of locus equation parameters to
      articulatory differences encountered in informal speech, stop place categories
      still maintained a clear separability when plotted in a higher-order slope x y
      intercept acoustic space.

PMID- 9933781
TI  - Relationship between rhythmic behavior and canonical babbling in infant vocal
      development.
AB  - The onset of canonical babbling (CB) is a landmark event in infants' vocal
      development for spoken language. Previous research has suggested that the onset
      of CB coincides with the peak period of rhythmic activities. To examine this
      phenomenon in detail, 28 Japanese infants (14 girls, 14 boys) were observed
      longitudinally from the age of 5 to 9 months. In the experimental sessions, an
      audible or an inaudible rattle was placed into a hand of each tested infant. Then
      the number of times that the infant shook the rattle was counted. In the
      observational sessions, infants' spontaneous rhythmic activities under natural
      conditions were observed. The result shows that rhythmic activities reached their
      peak around the onset of CB. When the infants began to babble, they shook
      whichever rattle was in their hand, regardless of its audibility. After this
      period, they shook the audible rattles more frequently than the inaudible ones.
      These findings suggest that, around the onset of CB, infants learn to control
      their motor activities based on auditory feedback.

PMID- 9933782
TI  - Visual fields in Short-toed Eagles, Circaetus gallicus (Accipitridae), and the
      function of binocularity in birds.
AB  - Visual fields were determined in alert restrained birds using an ophthalmoscopic
      reflex technique. The region of binocular overlap is relatively small: maximum
      width of 20 degrees occurs approximately 15 degrees below the horizontal, and the
      field extends vertically through 80 degrees with the bill tip placed close to the
      centre. Monocular field width in the horizontal plane is 139 degrees, and the
      field is asymmetric about the optic axis. The cyclopean field extends through 260
      degrees, and the blind area above and behind the head reaches maximum width of
      100 degrees close to the horizontal. At the frontal margins of the monocular
      field the retinal and optical fields do not coincide; the retinal field margin
      lies approximately 10 degrees inside the optical margin. This gives rise to an
      apparent binocular field that is twice the width of the functional binocular
      field. Interspecific comparisons show that the binocular field of Short-toed
      Eagles is similar in shape and size to those of bird species that differ markedly
      in phylogeny, ecology, foraging technique, and eye size. This suggests that these
      relatively narrow binocular fields are a convergent feature of birds whose
      foraging is guided by visual cues irrespective of whether items are taken
      directly in the bill or in the feet, as in eagles, and irrespective of the size
      and shape of the monocular and cyclopean visual fields. It is argued that
      binocular vision in birds results from the requirement for each monocular field
      to extend contralaterally to embody a portion of the optical flow field which is
      radially symmetrical about the direction of travel. This is in contrast to
      functional explanations of binocularity, such as those concerned with stereopsis,
      which present it as a means of extracting higher order information through the
      combination of two monocular images of the same portion of a scene.

PMID- 9933783
TI  - Morphology and dye-coupling of cells in the pigeon isthmo-optic nucleus.
AB  - Ground-feeding birds such as pigeons possess the most developed isthmo-optic
      nucleus in all classes of vertebrates. A previous study showed that this
      centrifugal or retinopetal nucleus modulates visual activity in tectal cells of
      pigeons; the present study aimed at revealing the morphology and possible dye
      coupling of neurons in the isthmo-optic nucleus and in the ectopic cell region by
      intracellular injections of Lucifer yellow into neurons in slices. One hundred
      and twelve successfully labeled cells of the isthmo-optic nucleus were classified
      into bipolar (83%) and multipolar (17%) types, each of which was further divided
      into two subtypes, B and P and M and N, respectively. Neurons of B- and P-types
      are similar in that they have apical dendrites and axons usually arising from the
      opposite pole of piriform perikarya, but they differ in the length (20-120 vs. 10
      20 microm) of their dendritic stems; M- and N-types possess polygonal perikarya
      giving rise to two to five primary dendrites either in the same orientation (M)
      or in a radiation fashion (N), and their axons originate from perikarya or
      occasionally from dendritic stems. Twelve single-injections resulted in the
      labeling of 26 cells, including 11 pairs and 1 quadruple labeling. About half of
      these are closely apposed 'twin-cells'. Dye-coupling was found only between
      neighboring cells in the cell lamina. Thirteen cells in the ECR rostroventral to
      the ION were labeled and could be grouped into large or L- (46%) and small or S-
      (54%) types, mainly depending on the dendritic field size and the number of
      primary dendrites. No dye-coupling was observed between the presumptive ECR
      cells. The functional role of the ION and the significance of dye-coupling
      between neurons are discussed.

PMID- 9933784
TI  - A quantitative analysis of cells in the ganglion cell layer of the chick retina.
AB  - This study investigated the organization of cells in the ganglion cell layer
      (GCL) using Nissl staining, retrograde cell degeneration with axotomy of the
      optic nerve, and retrograde cell labeling by injections of horseradish peroxidase
      (HRP) into the optic nerve of chicks (posthatching day 1 and 8, P-1 and P-8). The
      total number of cells in the GCL was 6.1 x 10(6) (P-1) and 4.9 x 10(6) (P-8), and
      the cell density was 14,300 cells/mm2 (P-1) and 10,400 cells/ mm2 (P-8) on
      average. Two high-density areas, the central area (CA) and the dorsal area (DA),
      were observed in the central and dorsal retinas in both P-1 (22,000 cells/mm2 in
      CA, 19,000 cells/mm2 in DA) and P-8 chicks (19,000 cells/mm2 in CA, 12,800
      cells/mm2 in DA). The cell densities in the temporal periphery (TP) and the nasal
      (NP) peripheral retinas were 7,800 cells/mm2 and 12,500 cells/mm2, respectively,
      in P-1 and 5,000 cells/ mm2 and 8,000 cells/mm2, respectively, in P-8 chicks. The
      cell density in the temporal periphery was 35% (P-8) lower than in the nasal
      periphery in both P-1 and P-8 chicks. Thirty percent (1.9 x 10(6) cells in P-1)
      of the total cells in the GCL were resistant to axotomy of the optic nerve. The
      distribution of the axotomy-resistant cells showed two high-density areas in the
      central and dorsal retinas, corresponding to the CA (5,800 cells/mm2) and the DA
      (3,200 cells/mm2). These cells also exhibited a center-peripheral increase (2,200
      cells/mm2 in the TP) in P-1 chicks, but the high-density area was not found in
      the dorsal retina of P-8 chicks. From these data and the HRP study, the number of
      presumptive ganglion cells in P-8 chicks was estimated to be 4 x 10(6) (8,600
      cells/mm2 on average), and the density in each area was 13,500 (CA), 10,200 (DA),
      and 4,300 (TP) cells/mm2. The peripheral/ center ratios of the density of
      ganglion cells were significantly different along the nasotemporal and
      dorsoventral axes. The density of ganglion cells decreased more rapidly toward
      the temporal periphery (TP/CA ratio: 0.47 in P-1 and 0.32 in P-8) than toward the
      nasal periphery (NP/CA ratio: 0.67 in P-1 and 0.52 in P-8). In contrast, there
      was no significant difference in the peripheral/center ratios between the dorsal
      retina (DP/CA ratio: 0.6 in P-1 and 0.56 in P-8) and ventral retina (VP/CA ratio:
      0.58 in P-1 and 0.51 in P-8). A small peak in the density of the presumptive
      ganglion cells was detected in the dorsal retina of both P-1 chicks (10,800
      cells/mm2) and P-8 chicks (10,200 cells/mm2). The HRP-labeled cells were small in
      the CA (M +/- SD: 35.7 +/- 9.1 microm2) and DA (40.0 +/- 11.3 microm2), and their
      sizes increased toward the periphery (63.4 +/- 29.7 microm2 in the TP)
      accompanied by a decrease in the cell density. However, the axotomy-resistant
      cells did not significantly increase in size toward the peripheral retina (12.2
      +/- 2.2 microm2 in the CA, 15.2 +/- 3.2 microm2 in the DA, 15.1 +/- 3.8 microm2
      in the TP). The characteristic distribution of ganglion cells could be related to
      visual behavior based upon the specialization of avian visual fields.

PMID- 9933785
TI  - Morphology of pyramidal neurones in cytochrome oxidase modules of the S-I bill
      representation of the platypus.
AB  - The primary somatosensory cortex of the platypus (Ornithorhynchus anatinus) is
      characterized by a distinct array of functionally specific cytochrome oxidase
      (CO) modules, forming alternate CO-rich and CO-poor bands. In the current study,
      we undertook to establish whether the cellular morphology of layer V pyramidal
      neurones reflects this modular organization. To this end, we injected neurones
      with Lucifer Yellow in 250 microm thick, flat-mounted cortical slices and
      processed the tissue to reveal a light-stable reaction product. By aligning blood
      vessels in serial sections in which we injected individual neurones with sections
      processed for CO, we were able to establish the exact location of injected cells
      with respect to the pattern of CO bands. Pyramidal neurones in the CO-poor bands
      (which are responsive to both mechano- and electroreceptive stimuli) had basal
      dendritic fields that were larger than those in the CO-rich bands. The large
      basal dendritic fields of layer V pyramidal neurones in the CO-poor bands may
      allow for integration of a greater number of more diverse inputs, thus allowing
      for averaging of stimuli to improve the signal-to-noise ratio or enhance spatial
      discrimination of peripheral stimuli. In some instances, neurones located within
      approximately 100 microm of the boundaries of the CO bands had dendritic fields
      that appeared to conform to the CO bands, the dendrites preferentially arborizing
      within a single band and avoiding the neighbouring band. However, the bias was
      not absolute, as we observed many examples of cells with dendrites that crossed
      the boundary between bands. Furthermore, many cells had dendrites that showed
      distinct dendritic bias that bore no obvious relationship to the CO boundaries.

PMID- 9933786
TI  - Immunohistochemical distribution of neuropeptide Y-related substance in the brain
      and hypophysis of the arctic lamprey, Lethenteron japonica.
AB  - The distribution of neuropeptide Y (NPY)-like immunoreactivity in the brain and
      hypophysis of the arctic lamprey, Lethenteron japonica, was studied by the use of
      polyclonal anti-synthetic porcine NPY antibody. Immunoreactivity was found
      throughout the brain, with varied densities among different areas. NPY-positive
      cell bodies were located in the dorsal pallium of the telencephalon; in the
      preoptic area, the thalamus, and the hypothalamus of the diencephalon; in the
      tegmentum of the mesencephalon; and in the octavolateralis nucleus, the middle
      reticular nucleus, and the vagal motor nucleus of the rhombencephalon. The
      majority of the NPY-positive cells in the thalamus and in the hypothalamus
      appeared as cerebrospinal fluid-contacting neurons. NPY-positive fibers were
      widely distributed in the brain and locally dense in the ventromedial part of the
      lateral pallium, in the posterior part of the interpeduncular nucleus, and in the
      raphe region. Conversely, they were less dense or well scattered in the olfactory
      bulb, the lateral pallium except for its ventromedial part, and the optic tectum.
      NPY-positive innervation in the neurohypophysis was evident, suggesting that
      involvement of NPY-related substance in the hypothalamo-hypophysial system had
      occurred in an early stage of vertebrate evolution.

PMID- 9933787
TI  - Curriculum in Urology: Phimosis and Circumcision in Children.

PMID- 9933788
TI  - Vascular endothelial growth factor: an important angiogenic mediator in bladder
      cancer.
AB  - Angiogenesis is the growth of new blood vessels from existing ones and is
      critical for tumour development, invasion and metastasis. In bladder cancer the
      prognostic significance of mean vascular density, a surrogate for angiogenesis,
      has lead to study of the factors determining the angiogenic phenotype. The
      motivation for these studies has been the search for non-invasive prognostic or
      diagnostic markers for the disease and for new therapeutic strategies against
      bladder cancer recurrence and progression. Whilst a large number of factors are
      involved in the mediation of tumour angiogenesis, vascular endothelial growth
      factor (VEGF) is widely considered to be central to the process. This review
      highlights the information presently available regarding the role of VEGF in
      bladder cancer through observational studies of its expression in bladder tumours
      and within the urine. In addition the value of VEGF in determining the prognosis
      in bladder cancer and the future possibilities for anti-VEGF therapy are
      discussed.

PMID- 9933789
TI  - Contrast angiosonography: a technology to improve Doppler ultrasound examinations
      of the prostate.
AB  - OBJECTIVES: A feasibility study to evaluate whether analysis techniques adapted
      from X-ray angiography can be used to analyze the transient enhancement of
      prostate blood flow patterns in color Doppler maps as obtained after
      administering ultrasound contrast agents. METHODS: Injections of ultrasound
      contrast agents were given to dogs and humans, and color Doppler blood flow
      patterns in fixed transverse sections through the prostate were recorded on video
      tape. Computer assistance of Doppler signals over time is used to evaluate the
      transient enhancement of flow patterns obtained with contrast-enhanced Doppler
      ultrasound. Results are compared to indicator dilution curve theory as used in,
      e.g., X-ray angiography. RESULTS: Administering a contrast agent to improve color
      Doppler evaluation of prostate blood flow resulted in clear enhancement of
      Doppler signal intensities without unwanted side effects. Using the computer, the
      perfused area of the prostate could be obtained quantitatively over time showing
      profiles of individual heartbeats. Averaging the perfused area over one heartbeat
      resulted in an indicator dilution curve, and correlation with dilution theory
      indicated the feasibility of applying wash-in and wash-out analysis of contrast
      agents in color Doppler images. CONCLUSION: Frame-by-frame interpretation by the
      computer indicated the feasibility of analyzing the transient enhancement of
      blood flow visibility in the Doppler image over time using techniques such as
      wash-in and wash-out time. This technology provides researchers in the field of
      ultrasound evaluation of the prostate the opportunity to apply a new diagnostic
      tool, contrast angiosonography, in their research. This method for analysis of
      prostatic blood flow can be helpful in any application that affects the blood
      supply of the prostate such as heat treatments and hormonal treatments.

PMID- 9933790
TI  - Follow-up in prostate cancer patients: which parameters are necessary?
AB  - AIM: In a retrospective study we examined whether follow-up of prostate cancer
      (PC) patients can be managed by using prostate-specific antigen (PSA) as a unique
      tool as postulated recently. PATIENTS AND METHODS: According to strict criteria
      established in the eighties, at our institution PC patients were monitored by
      PSA, prostatic acid phosphatase (PAP), alkaline phosphatase (AP), digital-rectal
      examination, renal and bladder ultrasound every 3 months, abdominopelvic
      computerized tomography (CT) and bone scan every 6 months. Between 1988 and 1994,
      80 patients with PC cancer were eligible (mean follow-up 29.5, range 12-81
      months). Patients were categorized into 4 groups: localized tumor (n = 44); lymph
      node metastases (n = 9); distant metastases (n = 18), and lymph node and distant
      metastases (n = 9). The parameters mentioned were compared for the assessment of
      progression, regression and stabilization of the disease. RESULTS: Our
      examinations showed that PSA is superior to all the other parameters used. In all
      groups, there were no patients with progressive disease detected by PAP, AP, CT
      and bone scan, but not by PSA. PSA anticipated the other parameters in detecting
      progression by several months. Renal ultrasound, however, detected new
      hydronephrosis in 6 patients with stable or decreasing PSA. Hydronephrosis was
      caused by surgery or radiotherapy, not by progressive PC. CONCLUSION: PSA can be
      used as a unique tool in the follow-up of PC patients in all stages. However,
      patients who underwent therapy potentially afflicting the urinary tract should
      have additional renal and bladder ultrasound.

PMID- 9933791
TI  - Final results of a screening campaign for prostate cancer.
AB  - OBJECTIVE: To detect curable prostate cancer in a male Spanish population. The
      results of screening 2,576 men are reported. PATIENTS AND METHODS: Patients
      underwent digital rectal examination (DRE) and serum prostate-specific antigen
      (PSA) determination. Any patient with suspicious DRE or PSA > 4 ng/ml was further
      evaluated with transrectal ultrasonography (TRUS) and biopsy. The sensitivity,
      specificity and predictive value of the tests or combinations of tests were
      determined. RESULTS: Mean age was 59.9 years (median 58 years). Ninety-four
      patients (3.6%) had abnormal DRE while PSA was > 4 ng/ml in 169 patients (6.5% of
      the total). We needed 6.8 biopsies to prove one cancer. PSA had the highest
      sensitivity (93%), whereas DRE had the highest specificity (97%). The positive
      predictive value rose to 78.9% when both DRE and PSA were abnormal. Clinically
      advanced tumor stages (> or = T3) were commoner (39.4%) than in similar series.
      CONCLUSIONS: PSA should be the first diagnostic test in a screening program for
      prostate cancer. Neither DRE nor TRUS are necessary in patients with PSA < 4
      ng/ml. In the light of our findings, we cannot encourage screening programs for
      prostate cancer for the time being.

PMID- 9933792
TI  - Estimation of prostate cancer volume by endorectal coil magnetic resonance
      imaging vs. pathologic volume.
AB  - OBJECTIVE: Since tumor volume is recognized as an important predictor of clinical
      stage and disease outcome of prostate cancer, accurate preoperative estimation of
      tumor volume can play an important role in planning the appropriate treatment and
      establishing a patient's prognosis. We performed this study to evaluate the
      accuracy of the endorectal coil magnetic resonance (MR) technique for reliable
      prediction of tumor volume in patients with prostatic cancer. MATERIAL AND
      METHODS: Endorectal coil MR imaging was performed in 57 consecutive men who were
      suspected to have prostate cancer. Subsequent ultrasound-guided transrectal
      biopsy revealed prostate cancer in 44 cases. The pathological volume of the
      surgical specimens of 25 selected patients who underwent radical prostatectomy
      was retrospectively compared to the volume estimated by endorectal coil MR
      studies, and the Pearson correlation coefficient was calculated. RESULTS: In 15
      patients the estimated size of the tumor was within 15% of the true tumor volume;
      in the remaining 10 cases MR imaging tended to underestimate large tumors and
      overestimate small ones. A significant correlation between the volumes as
      determined with MR imaging and measurements of surgical specimens was observed (r
      0.94; slope 0.82). To our knowledge, this is the best correlation found between
      pathological volume and tumor volume as evaluated by any other imaging modality.
      CONCLUSIONS: Endorectal coil MR imaging is a powerful means of evaluating the
      prostate gland; however, further improvements in imaging and/or volume
      calculation are required to provide a more accurate preoperative assessment of
      prostate cancer volume.

PMID- 9933793
TI  - A review of the complications and results of implantation of the AMS artificial
      urinary sphincter.
AB  - The history and evolution of devices designed to achieve urinary continence are
      reviewed. Passive and active (including volume and pressure regulated) devices
      are described in detail. Meta-analysis of the published studies revealed that
      continence improved in 88% of patients and total continence was achieved in 73%.
      Global revision rate was 32%. Urethral erosion occurred in approximately 12%,
      infection in 4.5% and mechanical complications in 14% of cases. The complications
      relating to the AMS artificial urinary sphincter are analyzed. The majority of
      patients (> 85%) required only one revision. 22% of complications were due to
      mechanical malfunction. Infection comprised 12.9% of complications. The patterns
      of total revisions followed a double exponential decay curve: 50% of revisions
      were performed within 8 months and 90% within 3 years of implantation.
      Complications were still reported several years postimplantation. This review
      analyzes the problems relating to the application of pressure and the presence of
      foreign material around the urethra and exemplifies the requirement for long-term
      specialist follow-up of these patients.

PMID- 9933794
TI  - A multicenter placebo-controlled, double-blind trial of urapidil, an alpha
      blocker, on neurogenic bladder dysfunction.
AB  - OBJECTIVES: To assess the efficacy of urapidil, an alpha-blocker, on neurogenic
      bladder dysfunction in a placebo-controlled, double-blind trial. METHODS: 149
      patients were randomly assigned to receive a placebo or 60 mg/day of urapidil for
      4 weeks. The evaluation of efficacy included changes in urinary symptom scores
      and the results of a pressure/flow study. RESULTS: There were significant
      intergroup differences with regard to straining and the sum of urinary symptom
      scores, with the urapidil group showing marked improvements (p = 0.016 and p =
      0.011, respectively). In the urapidil group, the average and maximum flow rates
      were unchanged, but the residual urine volume decreased significantly (p < 0.001)
      as compared with the baseline value. The pressure at maximum flow and the minimum
      urethral resistance decreased significantly (p = 0.040 and p = 0.040,
      respectively) in the urapidil group, and there was a significant (p = 0.005)
      intergroup difference with regard to pressure at maximum flow. There was also a
      significant (p < 0.001) inter-group difference with regard to the overall
      therapeutic effect. Side effects were noted in 2 patients treated with urapidil
      and 6 in the placebo group. CONCLUSION: Urapidil is effective for the treatment
      of voiding dysfunction in patients with neurogenic bladder.

PMID- 9933795
TI  - Comparison of the BTA stat test with voided urine cytology and bladder wash
      cytology in the diagnosis and monitoring of bladder cancer.
AB  - OBJECTIVE: To compare the BTA stat test (BTA stat), a new one-step
      immunochromatographic assay that can be performed in the urologist's office or in
      the laboratory, to voided urine cytology and bladder wash cytology (cytology) in
      the diagnosis and monitoring of cancer of the bladder (BC). METHODS: BTA stat and
      cytology were performed in a double-blinded, prospective, clinical study on
      specimens from 240 subjects (68 females; mean age of subjects: 64 years)
      suspected of having BC. RESULTS: In 107 subjects with final diagnoses of BC
      confirmed by cystoscopy or cystoscopy and biopsy, the overall sensitivities of
      BTA stat and cytology were 65 and 33%, respectively. For tumor grades I, II, and
      III, the sensitivities of BTA stat were 39, 67 and 83%, respectively. Those of
      cytology were 4, 20 and 69%. Nine subjects had a diagnosis of 'suspicious for
      bladder cancer'. The specificities of BTA stat and cytology in the 124 subjects
      without BC were 64 and 99%, respectively. In the subjects with a history of BC (n
      = 74), the specificities of BTA stat and cytology were 72 and 99%, respectively.
      The specificity of BTA stat was lower in subjects with benign or malignant
      genitourinary disease other than BC (46%) than in subjects without genitourinary
      disease (71%). CONCLUSIONS: The BTA stat test is considerably more sensitive than
      cytology in the detection of BC and can replace cytology as an adjunct to
      cystoscopy in the diagnosis and follow-up of patients with BC. However, due to
      low specificity, BTA stat should not be used without first ruling out potential
      interferences such as infections, renal disease and cancer, or genitourinary
      trauma.

PMID- 9933796
TI  - Assessment of lower urinary tract dysfunction in children with non-neuropathic
      bladder sphincter dysfunction.
AB  - Although nonneuropathic bladder sphincter dysfunction in children is frequently
      encountered, there is no consensus on the assessment of children presenting with
      this problem. An example is given of how these children can be assessed. After a
      noninvasive screening consisting of history, voiding diary, clinical examination,
      urinalysis, ultrasound and uroflowmetry, those children that will benefit from
      further videourodynamic studies are selected. Videourodynamics help to describe
      accurately the filling phase dysfunction and the voiding phase dysfunction, which
      helps to outline therapy. By using the described methods we are able to select
      those patients who will benefit from pharmacotherapy and those who will benefit
      from urotherapy.

PMID- 9933799
TI  - Curriculum in urology: septicaemia and shock 

PMID- 9933797
TI  - Pro-inflammatory and T cell inhibitory cytokines are secreted at high levels in
      tumor cell cultures of human renal cell carcinoma.
AB  - OBJECTIVES: The objectives of this study were to assess cytokine secretion in
      human renal cell carcinoma (RCC) and to identify cytokines contributing to the
      immunomodulatory effect of tumor cells. METHODS: Cytokine secretion in the
      supernatant of primary tumor cell cultures (PTCC) and corresponding cell lines
      (CL) was assayed using ELISA. Tumor cells were characterized by morphology,
      immunocytochemistry, and flow-cytometric analysis. Tumor-cell-induced T cell
      activation was determined by coculture of gamma delta and alpha beta T cell
      clones with tumor CL. RESULTS: We assessed the cytokine secretion of tumor cells
      from 27 PTCC and their corresponding CL (3/27) of RCC. We found that RCC
      predominantly produced both pro-inflammatory and T-cell-inhibitory cytokines,
      such as IL-8, IL-6, GM-CSF, TNF-alpha, IL-10 and TGF-beta 1. CL were adapted to
      serum-free medium which may prove as a useful tool in future studies of cytokine
      secretion in RCC. In addition, we used gamma delta and alpha beta T cell clones
      to assess the immunomodulatory effect of tumor cells from RCC and found that
      predominantly gamma delta T cells were activated by RCC. CONCLUSIONS: Our data
      suggest that RCC produce large amounts of both pro-inflammatory and T-cell
      inhibitory cytokines that potentially could influence the immune response of the
      host, especially tumor-specific cytotoxic T cells.

PMID- 9933798
TI  - Quantitative detection of human complement factor H-related protein in
      transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVE: The purpose of this study was to assess a new quantitative urinary
      tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human
      complement factor H-related protein (hCFHrp, BTA TRAK). METHODS: Urine samples of
      298 individuals (76 healthy volunteers, 118 patients with benign urologic
      disorders, 104 patients with histologically proven bladder cancer) were examined
      for the presence of hCFHrp. Samples of all patients were obtained prior to
      therapy. RESULTS: In comparison to healthy volunteers, patients with TCC had
      significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001).
      HCFHrp levels were positively correlated with tumor grade and stage. Patients
      with invasive TCC had significantly higher levels of hCFHrp than patients with
      superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high
      risk of tumor progression (pT1G3) were significantly higher as compared to low
      and intermediate grade superficial cancers. Elevated levels of hCFHrp were also
      found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml
      in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of
      72.1% and, due to a high rate of false-positive determinations in patients with
      benign urologic disorders, a total specificity of 50.5%. CONCLUSIONS: HCFHrp (BTA
      TRAK) is a sensitive test for detection of bladder cancer and for identification
      of patients at high risk. Due to a high rate of false-positive results in
      patients with benign urologic diseases, the test should not be used in an
      unselected population.

PMID- 9933800
TI  - BTA stat and BTA TRAK: A comparative evaluation of urine testing for the
      diagnosis of transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: We compared the BTA (bladder tumor antigen) stat test with the BTA
      TRAK assay in patients highly suspicious of bladder cancer. METHODS: The BTA stat
      and the BTA TRAK tests are two immunoassays that detect human complement factor H
      related protein in urine, employing the same antibody pair. The BTA stat is a
      qualitative test which can be performed in a consultation setting. The BTA TRAK
      is a quantitative test that is performed in the laboratory. Consecutive patients
      highly suspicious of bladder cancer were included in this prospective blinded
      trial to assess the clinical performances of the two methods. RESULTS: A total of
      81 patients were tested using BTA stat and BTA TRAK before cystoscopy. A tumor
      was identified in 49 patients. BTA TRAK (38/49 true-positive cases) was more
      sensitive than BTA stat (32/49) in detecting bladder cancer (p < 0.05). When
      considering the subgroups of bladder cancer by stage and grade, the difference
      remained significant for low-grade and low-stage tumors. There was no significant
      difference between BTA TRAK and BTA stat as regards specificity (20/32 and 23/32
      true-negative cases, respectively; p = 0.2). CONCLUSION: BTA TRAK with a cutoff
      of 14 U/ml had a significantly higher sensitivity than BTA stat in the detection
      of low-grade and low-stage bladder cancer.

PMID- 9933802
TI  - Abnormal patterns of mucin secretion in ileal neobladder mucosa: evidence of
      preneoplastic lesion?
AB  - In gastric and colonic mucosa the abnormal pattern of mucin secretion has been
      related to an increased risk of malignant changes. The short- and long-term
      histologic and histochemical changes in the mucin content of the ileal mucosa
      have been studied in 180 biopsies from 90 male patients 6-96 months after radical
      cystectomy and urinary diversion via an orthotopic neobladder. Up to 3 years
      after surgery, histologic changes comprise a shortening of the villi and an
      increase in the number of goblet cells. Concomitantly, an abnormal pattern of
      mucin secretion, with a predominant secretion of sulfomucins, is demonstrable.
      After 3 years of follow-up, the mucosa progressively flattens and mucin
      production reduces; after 6 years, the prevalent finding is a flat, avillous
      epithelium without evidence of mucin secretion. There was no dysplasia or
      malignancies in any of the patients. The changes in the pattern of mucin
      production are not potential preneoplastic lesions, but represent a transient
      defence mechanism of the ileal mucosa exposed to urine.

PMID- 9933801
TI  - Evaluation of urinary level of NMP22 as a diagnostic marker for stage pTa-pT1
      bladder cancer: comparison with urinary cytology and BTA test.
AB  - BACKGROUND: In the present study we compared the clinical value of two new
      specific tests for transitional cell carcinoma, urinary nuclear matrix protein
      (NMP22) levels and bladder tumor antigen (BTA) test, with that of urinary
      cytology in the follow-up of patients with superficial bladder cancer. MATERIALS
      AND METHODS: Hundred and five bladder cancer patients were recruited: 30 stage
      pTa and 45 stage pT1 (group A), and 30 with a history of bladder cancer but no
      recurrence at the time of the study (group B). Urine samples were collected
      before any instrumental manipulation of the genitourinary tract. All patients
      were negative for urinary tract infections at conventional urine analysis.
      RESULTS: NMP22 at a cutoff value of 6 U/ml showed a sensitivity of 83.3% in pTa
      cases and 97.7% in pT1 cases, with a false-positive rate of 23.3%. The BTA test
      was positive in 26.6% of patients with cancer stage pTa and in 66.6% of pT1
      stage, with 30% false-positives in the non-neoplastic group. Urinary cytology,
      performed on three consecutive samples, was positive in 20% of patients with
      cancer stage pTa and in 64.4% of pT1 stage and did not show any false-positive
      cases. Stratifying the neoplastic patients according to lesion grade, NMP22 (at a
      cutoff value of 6 U/ml) was positive in 86.2% of G1, 97.2% of G2 and 90% of G3.
      BTA was positive in 37.9, 52.7 and 70% of G1, G2 and G3, respectively, while
      urinary cytology was positive in 37.9, 44.4 and 80%.

PMID- 9933803
TI  - MR urography in the diagnosis of urinary tract obstruction.
AB  - OBJECTIVE: To evaluate the efficiency of MR urography in depicting the urinary
      tract. METHODS: 33 patients with urinary tract abnormalities were additionally
      evaluated with MR urography. 25 had dilated upper urinary tracts because of
      urinary obstruction and 8 had normal tracts. MR urography was performed with a
      1,5T magnet using a heavy T2w sequence (3D-IR-TSE) in the coronal plane. Images
      were post-processed using the MIP algorithm. Both reconstructed and source images
      were evaluated. The results of MR urography were compared with the final
      diagnosis, which was established surgically in 23 cases, and with multimodality
      imaging workup in 10 cases. RESULTS: MR urography correctly depicted the level of
      obstruction and the degree of dilatation of the urinary tract in all 25 patients
      with hydronephrotic kidneys (sensitivity 100%). Additionally, it succeeded in
      suggesting the underlying pathology in 25 cases (48%). Concerning the 8 patients
      without dilatation of the urinary tract, there was either no depiction or
      depiction was bad. CONCLUSION: MR urography, a new noninvasive technique,
      demonstrates 100% sensitivity in diagnosing urinary tract obstruction and also
      suggests the underlying pathology in many cases. In nondilated systems it is not
      possible to get good images because MR urography only depicts fluid in the
      urinary tract. Thus we believe that MR urography can provide a reliable
      alternative in selected cases as opposed to other more invasive modalities, such
      as retrograde or antegrade urography, and is without the risk of contrast media
      and radiation exposure.

PMID- 9933804
TI  - Comparison of microvascularization in diagnostic needle biopsies and radical
      prostatectomies in prostate carcinoma.
AB  - OBJECTIVES: Quantitation of microvessel density has been shown to predict tumor
      aggressiveness in prostate carcinoma (Pca). The correlation of estimated values
      of angiogenesis in needle biopsy and radical prostatectomy materials might show
      the efficiency of the diagnostic biopsy material to represent a good sample of
      the entire tumor. In this study, we assessed the correlation of
      microvascularization computed by morphometric methods in biopsy and radical
      operation materials. METHODS: Sections from diagnostic biopsy and radical
      prostatectomy materials of 23 patients with Pca were stained with factor- 8
      associated antigen by immunohistochemistry and vascular surface density (VSD),
      microvessel numbers (NVES) and maximum microvessel number (NVES-MAX) were
      assessed by stereological methods. The microvascularization values in biopsy and
      radical operation materials were compared by Wilcoxon signed-ranks test for
      paired samples. RESULTS: No significant difference was observed between VSD and
      NVES values that were obtained from biopsy and radical operation materials of the
      same cases (p = 0.2478 and 0.3458, respectively). However, a significant
      difference was noted for NVES- MAX (p = 0.0004). CONCLUSION: We have shown, in a
      limited number of cases, that microvascularity prediction by stereological
      analysis using VSD and NVES in diagnostic needle biopsies correlates well with
      the radical operation specimens. Preoperative biopsies may predict overall tumor
      neovascularization characteristics that may have an impact on pathological stage
      and behavior.

PMID- 9933805
TI  - Transurethral needle ablation (TUNA). A critical review of radiofrequency thermal
      therapy in the management of benign prostatic hyperplasia.
AB  - Radiofrequency thermal therapy of the prostate is a new minimally invasive
      treatment for symptomatic benign prostatic hyperplasia (BPH). The procedure is
      called transurethral needle ablation (TUNA). With TUNA, the inner region of the
      prostate is selectively ablated with temperatures approaching 90-100 degrees C
      while the prostatic urothelium is preserved. The objective of this article is to
      discuss the basics of radiofrequency energy, instrumentation, surgical
      techniques, and to present an update of the clinical results as it applies to the
      treatment of BPH.

PMID- 9933806
TI  - Transurethral microwave thermotherapy.
AB  - OBJECTIVES AND METHODS: The present status of transurethral microwave
      thermotherapy (TUMT) in the low (LE) and high energy (HE) version is given as an
      overview. RESULTS: With LE software, approximately 75% of patients will note
      significant improvement with 65% reduction in symptom scores and a 35-40%
      improvement in peak flow rate. Sham studies have shown statistically significant
      improvement in treated patients compared to sham. Randomized studies between TUMT
      and TURP show similar improvements in symptom scores with TURP producing higher
      flow rates, as expected. Long-term studies have been reported to 5 years showing
      durability, although 10-20% of patients subsequently undergo TURP. The clinical
      efficacy of HE-TUMT 2.5 has been documented in recently completed studies.
      Approximately 37% of patients develop cavitation with HE-TUMT. The symptomatic
      improvement is similar between low and high energy while the flow rates with high
      energy improve by approximately 65%. Pressure flow studies have documented relief
      of obstruction in most of those patients who had obstruction prior to treatment.
      The morbidity of HE-TUMT in terms of retrograde ejaculation and posttreatment
      retention is higher compared to the LE version. CONCLUSIONS: TUMT is a 1-hour out
      patient, local anesthetic procedure, minimally invasive treatment option for
      benign prostatic hyperplasia that encompasses microwave radiative heating and
      water conductive cooling. TUMT has been proven both safe and efficacious for
      relieving benign prostatic hyperplasia symptoms in several large-scale controlled
      studies. The existence of low and high energy versions offers the opportunity to
      select patients according to obstruction grade.

PMID- 9933807
TI  - Side-firing Neodymium:YAG laser prostatectomy.
AB  - Not until 1991 did laser therapy for benign prostatic hyperplasia become a
      feasible option for the practicing urologist. Prior to the development of side
      firing free beam laser delivery devices contact Neodymium:YAG, laser therapy for
      BPH was of limited applicability. Since 1991, refinements in laser device
      technology have allowed the urologist to expand the potential for Neodymium:YAG
      coagulative prostatectomy. Multiple studies over the past five years have
      demonstrated equivalence in efficacy and safety to conventional electrocautery
      TURP. Holmium:YAG laser technology may be a significant advance again on free
      beam side firing Neodymium:YAG laser prostatectomy.

PMID- 9933808
TI  - Interstitial laser therapy of benign prostatic hyperplasia.
AB  - The objective of interstitial laser coagulation (ILC) of benign prostatic
      enlargement is to achieve a marked volume reduction and to decrease bladder
      outlet obstruction and lower urinary tract symptoms with minimal morbidity.
      Coagulation necrosis is generated well inside the adenoma by means of
      specifically designed laser applicators combined with either a Nd:YAG laser or a
      diode laser. Because the laser applicators can be inserted as deeply and as often
      as necessary, it is possible to coagulate any amount of tissue at any desired
      location while preserving adjacent structures such as the urethra.
      Postprocedural, the intraprostatic lesions result in secondary atrophy and
      regression of the prostate lobes, rather than sloughing of necrotic tissue.
      Several single-armed and randomized studies indicated the effectiveness of
      interstitial laser coagulation of BPH-syndrome. Marked improvements in AUA score,
      peak flow rate, residual urine volume and prostate volume were reported. Pressure
      flow studies demonstrated a sufficient decrease of the intravesical/detrusor
      pressure, urethral opening pressure and urethral resistance. Long-term results
      demonstrating sustained success for up to 3 years were reported on a series of
      394 patients. ILC is suitable to debulk even large prostates and to treat highly
      obstructive patients. Therefore, ILC can be seen as a true alternative to TURP
      with certain advantages, such as almost no serious morbidity and with certain
      disadvantages, such as the need for postoperative catheterization. However, ILC
      can be done under local anesthesia and does not require hospitalization.

PMID- 9933810
TI  - Thick loop transurethral resection of the prostate.
AB  - OBJECTIVES: To evaluate the safety and efficacy of the new resection loops for
      transurethral resection of the prostate (TURP). These loops, which are both
      thicker and have a modified shape, allow simultaneous resection, increased tissue
      vaporization, and improved hemostasis. METHODS: Two open studies have been
      performed with the thick resection loop. In one series, 91 patients underwent
      TURP with the Vapor Cut (G. Vallancien, Paris), and in another series, 65
      patients underwent Wedge (Microvasive, Natick, Mass., USA) resection (A.
      Perlmutter, New York). RESULTS: At 1 year follow-up, patients who underwent thick
      loop resection enjoyed the same clinical benefit of thin loop TURP without
      additional morbidity. Peak urinary flow rate improved to 18.4 and 16.3 cm3/s at 1
      year with the Vapor Cut and Wedge, respectively. IPSS fell to 7.2 (Vapor Cut) and
      6.2 (Wedge). Postoperative bleeding, meatal stenosis, and urethral stricture were
      noted, but no impotence or incontinence was observed. CONCLUSIONS: Thick loop
      resection offers the advantage of improved surgical vision during resection, thus
      allowing a more accurate and safer resection. This can be performed with only
      minor modifications of the standard TURP technique.

PMID- 9933809
TI  - Holmium laser resection of the prostate.
AB  - OBJECTIVE: This review of holmium laser resection of the prostate (HoLRP)
      summarises the evolution, points of technique, results of clinical trials and
      ongoing research concerning this procedure. METHODS: Over 3 years of experience
      with holmium resection/enucleation in two institutions is reviewed. Several open
      studies and 2 randomised trials are presented and the results discussed. Current
      work with holmium enucleation of the prostate (HoLEP) in combination with
      intracavitary morcellation is also reported. RESULTS: HoLRP results in fewer
      blood transfusions, less nursing contact time, less requirement for bladder
      irrigation, and a shorter catheter time and hospital stay than for patients
      treated with standard electrocautery resection of the prostate (TURP).
      Preliminary results suggest equivalent symptomatic relief, and relief of bladder
      outflow obstruction between the two procedures. CONCLUSIONS: Holmium
      prostatectomy continues to evolve. Preliminary experience suggests that it may be
      a viable alternative to TURP and appears to have some significant advantages.
      Newer techniques for tissue retrieval may significantly decrease the operating
      time.

PMID- 9933811
TI  - Electrosurgery: VaporTrode.
AB  - Despite subjective and objective success rates approaching 90%, significant
      morbidity is well documented using a wire loop for standard transurethral
      resection of the prostate (TURP). In an effort to minimize patient morbidity as
      well as limit future healthcare costs, several alternative instrumental
      techniques have been examined. Recent studies of transurethral
      electrovaporization of the prostate, a modification of existing transurethral
      technology, appear encouraging. The modifications which enable larger volumes of
      tissue to be vaporized with concurrent desiccation and coagulation are an
      increase in the surface area of the electrode and effective delivery of high
      electrical energy by electrical generators. The most extensively studied
      instrument is the VaporTrode. Promising early published reports of TURP-like
      efficacy without significant morbidity, as well as low cost, have fueled the
      popularity and wide application of this technique.

PMID- 9933812
TI  - Future perspectives.

PMID- 9933813
TI  - Primary fetal hydrothorax: A literature review and proposed antenatal clinical
      strategy.
AB  - OBJECTIVE: To investigate the prognostic factors for primitive fetal hydrothorax
      (PFHT) and propose a clinical strategy based on systematic literature review.
      METHODS: We reviewed 64 articles describing 204 cases of PFHT. For each case we
      focused on 11 criteria. We investigated prognostic factors in the 89 cases where
      no in utero treatment was undertaken. We also studied the impact of different in
      utero treatments on the evolution of PFHT. RESULTS: We have found 4 factors
      correlated with the course of PFHT: the presence of hydrops, gestational age at
      time of birth, the unilateral or bilateral nature of the effusion, and the
      occurrence of spontaneous resolution. With multivariate analysis, only hydrops
      remained determinant as a prognostic factor. CONCLUSIONS: Studies such as ours,
      reviewing case reports or series, are subject to the biases of literature
      underreporting of therapeutic failures or nonintervention. However (with the best
      available data) we propose a clinical approach to PFHT discovered in utero.

PMID- 9933814
TI  - Changes in survival of twins delivered after twin-twin transfusion syndrome
      versus preterm singletons over the calendar years 1970-1994.
AB  - OBJECTIVE: The use of serial amniotic fluid volume reduction for the treatment of
      twin-twin transfusion syndrome (TTTS) became available about 1986 and may account
      for a recent increase in survival of TTTS twins. To determine whether the
      increase in survival has been due to advances in neonatal care rather than the
      advent of amnioreduction, the current study evaluated whether increases in
      survival of preterm TTTS twins were greater than increases in survival of preterm
      singletons from studies before 1986 compared to studies after 1986. METHODS:
      Medline literature search identified all reported cases of TTTS and all reports
      of severely preterm neonatal survival. Studies were divided into groups according
      to gestational age at birth (</=27 vs. >27 weeks) and midyear of each study
      (</=1986 vs. >1986). Comparison was performed of the increase in survival from
      pre-1986 studies to post-1986 studies between preterm singletons and TTTS twins.
      RESULTS: When comparing studies from before 1986 to after 1986, there was no
      difference in the increase in survival between preterm (>27 weeks) TTTS twins (67
      92%) and preterm (>27 weeks) singletons (79-91%) (p = NS). When comparing studies
      from before 1986 to after 1986, there was a greater increase in survival among
      severely preterm (</=27 weeks) TTTS twins (0-22%) than among severely preterm
      (</=27 weeks) singletons (47-57%) (p = 0.036). CONCLUSIONS: Because of the
      paucity of data on TTTS twins and the retrospective nature of this study,
      conclusions are limited. There appears to be some basis for the belief that
      amnioreduction improves survival in TTTS twins delivered at </=27 weeks'
      gestation. These results confirm the need for a randomized, controlled trial of
      expectant management versus amnioreduction for the treatment of TTTS.

PMID- 9933815
TI  - Fetal glioblastoma: rapid growth during the third trimester.
AB  - We present a case of fetal glioblastoma which appeared after 28 weeks' gestation.
      The first ultrasonographic finding was an enlarged fetal head with right shifted
      falx cerebri at 31 weeks' gestation. At 33 weeks, a large and high echogenic mass
      in the left hemisphere and right enlarged ventricle was identified. Magnetic
      resonance imaging showed that the tumor was localized in the left hemisphere and
      a margin of the tumor was defined. Because fetal well-being judging from
      biophysical parameters was good and we considered that the tumor was resectable,
      a male fetus weighing 2,670 g was delivered at 34 weeks' gestation by cesarean
      section. However, he was inoperable due to consumptive coagulopathy and rapid
      growth of the tumor, and died on the 41st day of life.

PMID- 9933816
TI  - Intrathoracic alimentary tract duplication cysts treated in utero by
      thoracoamniotic shunting.
AB  - Alimentary tract duplication cysts are rarely diagnosed in utero. We report two
      fetal patients that presented with intrathoracic alimentary tract duplication
      cysts, mediastinal shift and hydrops. In one fetus, the cyst continued into the
      fetal abdomen and pelvis through a left diaphragmatic hernia. Despite successful
      ultrasound-guided needle aspirations in both fetuses, there was rapid
      reaccumulation of the fluid and recurrence of the mediastinal shift, prompting
      the placement of a thoracoamniotic shunt. In one fetus, there was rapid
      resolution of the mediastinal shift with the disappearance of the hydrops within
      2 weeks. The second fetus suffered an intrauterine demise 2 days after the shunt
      placement. Postnatal resection in the surviving infant revealed a large cyst
      consistent with an intrathoracic duplication of the stomach. The autopsy of the
      second fetus revealed an intrathoracic duplication cyst of the stomach and
      proximal small intestine.

PMID- 9933817
TI  - Perinatal findings in a male fetus with congenital megacystis and anorectal
      malformations.
AB  - We report the perinatal findings in a male fetus with congenital megacystis and
      anorectal malformations. A 17-year-old primipara was referred to our department
      at 13 weeks of gestation for management of a 4.6 x 3.8 cm massive intra-abdominal
      fetal mass consistent with megacystis. The fetal thorax was severely compressed.
      We used a 22-gauge needle to perform intrauterine fetal vesicocentesis, removing
      30 ml of fetal urine, decreasing the fetal bladder diameter/crown-rump length
      ratio from 65.7 to 17%. Cytogenetic analysis revealed a 46, XY karyotype.
      Intermittent bladder aspiration was performed weekly from 13 to 20 weeks of
      gestation and every 2-3 weeks from 21 to 35 weeks of gestation for the purpose of
      decompression. Mild dilation of both renal pelves was noted beginning at 20 weeks
      of gestation, however, neither progression of hydronephrosis nor development of
      oligohydramnios was noted. At 36 weeks of gestation, a live male neonate was
      delivered with a normal phallus, duodenal atresia, mild congenital heart defects,
      a distended bladder, bilateral hydronephrosis, megaureters, imperforate anus with
      rectovesical fistula, cryptorchidism and bilateral vesicoureteric reflux. The
      postnatal renal function was normal. He underwent serial operations including
      colostomy, anoplasty with repair of rectovesical fistula, duodeno-duodenostomy,
      bilateral re-implantation of ureters, orchiopexy and reduction cystoplasty. At 20
      months of age, the child had normal renal function. The intravenous pyelogram
      showed normal functional kidneys, moderate megaureters and moderate megacystis.
      He underwent clean intermittent catheterization for residual urine. The recurrent
      urinary tract infections were under control.

PMID- 9933819
TI  - A survey of attitudes about maternal serum screening for fetal chromosome
      abnormalities in women 35 years of age and older.
AB  - We asked two groups of women their opinion on prenatal diagnosis and maternal
      serum screening (MSS): group 1 comprised women who had undergone a prenatal
      diagnostic procedure (amniocentesis or chorionic villus sampling) for advanced
      maternal age (>/=35 years) and group 2 women who had undergone MSS and were 30-34
      years old. Women in group 1 were found significantly less likely to choose MSS
      over prenatal diagnosis than were women in group 2. The sensitivity of MSS and
      the age-related risk of chromosome abnormalities influenced opinions on whether
      to choose MSS or prenatal diagnosis. In both groups, the majority stated that
      they would accept MSS over prenatal diagnosis, if their obstetrician recommended
      it.

PMID- 9933818
TI  - Elevated second-trimester maternal urine free beta-human chorionic gonadotropin
      levels in Asian pregnancies with fetal chromosomal abnormalities.
AB  - OBJECTIVES: To investigate the second trimester maternal urine free beta-human
      chorionic gonadotropin (hCG) levels of chromosomally abnormal pregnancies in
      Asians. METHODS: Free beta-hCG levels were analyzed from the urine samples of 110
      control and 17 chromosomally abnormal pregnancies, including 11 cases of Down
      syndrome, 1 case of trisomy 18, and other chromosomal abnormalities (one mosaic
      deletion and 4 translocations) from the second trimester of pregnancy. Results
      were normalized to urine creatinine (Cr) concentration and converted to the
      multiple of the median (MOM) level for the appropriate gestation. Gestational age
      of all cases was determined by ultrasound parameters. RESULTS: The median free
      beta-hCG MOM levels of Down syndrome (4.02 MOM) and other chromosomally abnormal
      pregnancies (2.03 MOM) are significantly higher than that of normal pregnancies
      (0.99 MOM) (p = 0.002 and p = 0.024, respectively). Nine of 11 (81.8%) Down
      syndrome cases, one trisomy 18 case, and 2 of 5 (40%) other chromosomally
      abnormal cases would be expected to be above the 95th centile of the control
      values (2.95 MOM cut-off). CONCLUSION: Urine free beta-hCG could be a potential
      and useful marker in the detection of fetal Down syndrome and other chromosomal
      abnormalities in Asians.

PMID- 9933820
TI  - Rapid prenatal diagnosis of trisomy 21 by polymerase chain reaction- associated
      analysis of small tandem repeats and S100B in chromosome 21.
AB  - OBJECTIVES: The incidence of Down syndrome increases with maternal age and a
      rapid and accurate method for prenatal diagnosis is a necessity. This study was
      devised to evaluate and compare the methods for detecting trisomy 21 by
      polymerase chain reaction (PCR)-associated analysis of small tandem repeats (STR)
      of D21S11 and semiquantitative analysis of S100B of chromosome 21. METHODS: PCR
      was performed with DNA template obtained from 20 normal samples (10 blood, 10
      amniotic fluid) and 12 Down syndrome samples (10 blood, 2 amniotic fluid). 32P
      labelled primers for D21S11 and S100B were used. PCR products for D21S11 were
      subjected to polyacrylamide urea gel (6%) electrophoresis, followed by exposure
      to X-ray film, and then the densities of signals were recorded by densitometer.
      PCR products for S100B and insulin-like growth factor-I (IGF-I) as an internal
      control were subjected to agarose gel (2%) electrophoresis and the relative
      amounts of radioactivity in their products were measured to assess the
      quantitation of template DNA. RESULTS: Analysis of D21S11 STR showed equivalent
      triplets in 4 cases and unequivalent doublets (1:2) in 8 Down syndrome samples.
      The normal control group showed singlets in 5 cases and equivalent doublets in 15
      cases. In the analysis of S100B, the ratios of S100B to IGF-I was 1.4-1.6 in 7 of
      12 Down syndrome samples, while the ratios of S100B in all normal samples were
      close to 1.0. All the results were obtained within 24 h. The D21S11 STR analysis
      managed to distinguish more clearly between normal and trisomy 21, while
      semiquantitative PCR analysis of S100B was less able to assess trisomy 21.
      CONCLUSION: Prenatal diagnosis of trisomy 21 by PCR-associated STR analysis of
      D21S11 and semiquantitative analysis of S100B are useful, innovative, accurate
      and rapid diagnostic methods, while D21S11 STR analysis is more discriminating in
      detecting trisomy 21 and also may be employed in preimplantation diagnosis of
      Down syndrome.

PMID- 9933821
TI  - Screening for Down's syndrome and neural tube defect in Croatia. A regional
      prospective study.
AB  - OBJECTIVE: The purpose of this study was to investigate the efficiency of second
      trimester maternal serum screening for Down's syndrome and open neural tube
      defects using alpha-fetoprotein and free beta-human chorionic gonadotropin as
      serum markers. METHODS: 3, 188 women underwent testing between 14th and 22nd week
      of pregnancy. Of all tested patients, 25.4% were >/=35 years old. A cut-off risk
      of >/=1:250 for Down's syndrome and MS-AFP >/=2.0 MoM for open neural tube defect
      were considered screen-positive. RESULTS: The detection rate for Down's syndrome
      was 77.8% (7/9) with 8.2% screen-positive rate (7.9% false-positive rate). When
      evaluated separately, in patients younger than 35 and in those >/=35 years old,
      the screen-positive rates were 3.1 and 23.3%, respectively. A total of 52 (1.6%)
      were found screen-positive for open neural tube defect; 2 cases of encephalocela
      and 1 case of gastroschisis were confirmed prenatally. CONCLUSION: The
      respectable number of cases with trisomy 21 identified in this study confirms
      that routine mid-trimester screening for Down's syndrome including MS-AFP, free
      beta-hCG and maternal age is useful in identifying pregnancies at increased risk.

PMID- 9933822
TI  - Fetal cardiocentesis in care of severe Kell immunisation.
AB  - This case report demonstrates how severe a Kell immunisation can be. Fetal anemia
      and hydrops fetalis in the second trimester required six intrauterine
      transfusions, two by cardiocentesis. At 4 years of age the child has shown no
      abnormalities.

PMID- 9933823
TI  - Frequencies of fetal nucleated red blood cells in maternal blood during different
      stages of gestation.
AB  - Nucleated red blood cells (NRBCs) isolated by a triple density gradient from 100
      ml peripheral blood samples of 100 pregnant women and 30 women postpartum were
      subjected to morphological analysis and PCR quantitation. The number of NRBCs
      steadily increased from 5.3 (frequency: 2.4 x 10(-7)) in early gestation to 98.2
      (frequency: 4.2 x 10(-6)) near term. The number of male cells increased from 6
      (frequency: 2.7 x 10(-7)) in early gestation to a peak of 31 (frequency: 1.48 x
      10(-6)) in the second trimester, and slightly decreased to 27 (frequency: 1.31 x
      10(-6)) near term. Both NRBCs and male fetal cells rapidly disappeared after
      delivery. The result implies that a significant proportion of NRBCs in maternal
      blood are of fetal origin before 24 weeks of gestation while in late gestation
      the majority of NRBCs may be of maternal origin.

PMID- 9933824
TI  - Calcium-sensing receptor: regulation of electrolyte transport in the thick
      ascending limb of Henle's loop.
AB  - A calcium-sensing receptor (CaR) has functionally been described in the cortical
      thick ascending limb of Henle's loop (CTAL) of rat and mouse. This G protein
      coupled receptor activates phospholipase C and increases the intracellular Ca2+
      concentration. We observed that in the mouse CTAL cAMP formation, induced by 10(
      8) mol/l AVP, was inhibited by more than 90% when the extracellular Ca2+
      concentration ([Ca2+]e) was increased from 0.5 to 3 mmol/l. Measurements of
      transepithelial potential difference (PDte) in rat and mouse CTAL and medullary
      thick ascending limb (mTAL) segments and of transepithelial ion net fluxes in the
      mouse CTAL (isotonic perfusion conditions: 150 mmol/l NaCl in the lumen and bath)
      showed that an increase in the [Ca2+]e had no effect on basal and arginine
      vasopressin (AVP, 10(-10) mol/l)-stimulated transepithelial PDte, NaCl and Mg2+
      transport. However, Ca2+ reabsorption was strongly inhibited by increased
      [Ca2+]e. Addition of AVP reversed this inhibitory effect of increased [Ca2+]e.
      Under hypotonic perfusion conditions (lumen 50 mmol/l NaCl; bath 150 mmol/l
      NaCl), a high [Ca2+]e induced a 50% decrease in Mg2+ reabsorption which was
      restored by AVP. Under these conditions, the effects on Ca2+ transport described
      above were still observed. In conclusion, activation of the CaR in the mouse TAL
      has no effect on basal and AVP-stimulated transepithelial NaCl reabsorption
      despite its large inhibitory effect on cAMP synthesis. The CaR, however, could
      play a role in the regulation of transepithelial Ca2+ and Mg2+ reabsorption.

PMID- 9933825
TI  - Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal
      cells.
AB  - The accumulation of hyaluronan (HA) in the renal cortex is a characteristic
      feature of inflammatory renal diseases. Fragments of HA derived from high
      molecular weight precursors are known to display inflammatory effects in vitro
      and could, therefore, participate in immune renal injury. To understand the
      mechanisms of HA fragmentation in vivo we examined the expression of recently
      characterized mammalian hyaluronidases in normal and autoimmune kidneys and in
      cell lines. We found that transcripts for the lysosomal-type hyaluronidases Hyal1
      and Hyal2 were constitutively expressed in normal and autoimmune kidneys as well
      as in tubular epithelial cells and in a macrophage cell line. The expression of
      hyaluronidase genes in the cell lines did not increase in response to treatment
      with tumor necrosis factor alpha or gamma interferon. Interestingly, transcripts
      for the testicular-type hyaluronidase PH-20 (Spam1, Hyal3) were also detected in
      normal and autoimmune kidneys as well as in tubular cells and macrophages.
      Transcript levels were higher in kidneys from male mice as compared with age
      matched females. Again, transcript levels did not change in vitro in response to
      cytokines. We conclude that mRNA for three different hyaluronidases is found in
      murine kidneys. The functional role played by these hyaluronidases in the
      degradation and metabolism of HA remains to be investigated further.

PMID- 9933826
TI  - Effects of neutral endopeptidase inhibition in the rat remnant kidney model.
AB  - The orally active neutral metalloendopeptidase (NEP) inhibitor SCH34826 was given
      by oral gavage in a dose of 90 mg/kg twice daily for 3 days to rats with subtotal
      nephrectomy (n = 7) and effects were compared to a placebo group receiving
      phosphate buffer (n = 5). Inhibition of neutral endopeptidase in the remnant
      kidney was measured by in vitro autoradiography using the specific radioligand
      [125I]-SCH 47896. Treatment with the NEP inhibitor SCH34826 caused a 60%
      reduction in the neutral endopeptidase radioligand-binding site density in the
      kidneys of the SCH34826-treated animals compared to the placebo group (81.6+/-3.7
      versus 214.5+/-4.2 dpm/mm2, p<0.01). This was associated with a marked increase
      in urinary atrial natriuretic peptide (ANP) from 3,930+/-295 to 9,094+/-1,089
      pg/24 h in the SCH34826-treated group (p<0.01). Concomitantly there was a
      transient increase in natriuresis in the SCH34826-treated group [baseline 2.03+/
      0.55 to 3.77+/-0.58 mmol/24 h on treatment day 1 (p = 0.02) and 2.58+/-0.19
      mmol/24 h on treatment day 3 (p = 0.09)] which was not observed in the placebo
      group. Urinary protein excretion, glomerular filtration rate (determined by 99mTc
      DTPA clearance), systemic blood pressure, plasma ANP concentration and urinary
      cyclic GMP excretion were not changed by SCH34826 treatment. These results
      suggest that oral administration of the NEP inhibitor SCH34826 inhibits renal
      neutral endopeptidase, increases urinary ANP and modulates natriuresis without
      alteration of systemic blood pressure, plasma ANP and renin level, glomerular
      filtration or protein excretion.

PMID- 9933827
TI  - Renal potassium handling in aging rats.
AB  - Aging is often related to electrolyte disorders. This study was designed to
      evaluate the renal capacity for K+ handling of aging rats submitted to both
      extreme situations of K+ depletion and K+ loading. Aging rats were submitted to
      metabolic assessment, measurement of plasma aldosterone and determination of
      Na+,K+-ATPase and H+,K+-ATPase activity in the inner medullary collecting duct
      (IMCD). During K+ depletion, aging rats showed low values of urine K+ excretion.
      After 2 weeks of dietary K+ restriction, the plasma K+ levels of these animals
      reached 2.9+/-0.1 mEq/l without acid-base disorders. During K+ loading, aging
      rats showed a significant increase in urinary K+ excretion, with plasma K+
      remaining at normal levels (4.7+/-0.1 mEq/l). Plasma aldosterone levels were low
      in control aging rats but K+ intake modulated the levels of this hormone, with K+
      depletion reducing it and K+ loading significantly increasing it. Na+,K+-ATPase
      activity increased only in the initial portion of the IMCD of aging rats after 2
      weeks of K+ depletion. In the distal portion of the IMCD, Na+,K+-ATPase activity
      did not change. H+,K+-ATPase remained unchanged in both the proximal and distal
      portions of the IMCD of aging rats. During K+ loading, there was no change in
      Na+,K+-ATPase or H+,K+-ATPase activity in the proximal or distal portions of the
      IMCD of aging rats. This study suggests that the senescent kidney responded to K+
      conservation and excretion under the two extremes of low and high K+ intake.

PMID- 9933828
TI  - Superoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat.
AB  - In the present study the role of superoxide in the glomerular damage in the low
      dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12
      rats were infused for 1 h with 1.0 microgram/kg bw endotoxin via a permanent
      jugular vein cannula. Of these rats, 6 were treated with SOD both prior to
      endotoxin infusion (7,000 U/kg) and 30 min (7,000 U/kg) and 4 h (14,000 U/kg)
      after the start of the infusion (SOD rats). The other 6 rats received no SOD
      treatment (endotoxin rats). Control pregnant rats were infused for 1 h with
      saline (saline rats; n = 6). Urinary albumin was measured on days 15 and 19 of
      pregnancy. On day 21, rats were sacrificed and kidney specimens were snap-frozen.
      Cryostat kidney sections were stained for fibrinogen, ecto-ATP diphosphohydrolase
      (e-ATPase) activity, polymorphonuclear cells, monocytes and various adhesion
      molecules on the endothelium and the leukocytes. SOD treatment appeared to
      significantly prevent the increased urinary albumin excretion and the decrease of
      glomerular e-ATPase activity which were observed in endotoxin-treated rats. This
      effect of SOD treatment after endotoxin infusion was associated with a
      significant inhibition of glomerular monocyte influx and a significant inhibition
      of adhesion molecule expression (glomerular ICAM-1 and VCAM-1 and leukocyte LFA-1
      and VLA-4). The present data suggest that in the endotoxin-infused pregnant rat,
      production of superoxide in the first few hours after the infusion plays a role
      in the induction of glomerular damage, leading to albuminuria and diminished e
      ATPase expression during the following days.

PMID- 9933829
TI  - Urinary dopamine and renal handling of L-DOPA in fasted spontaneously
      hypertensive rats.
AB  - A defective renal dopaminergic system has been suggested to contribute, via
      impaired sodium excretion, to the pathogenesis of hypertension. Data according
      renal dopamine (DA) release in hypertension, however, are inconsistent. In the
      present study, we compared urinary DA excretion (UDAV), plasma free DA (PDA), and
      renal tissue DA contents (TDA) of young spontaneously hypertensive rats (SHR),
      Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. Since the protein intake
      dominantly controls UDAV, fasted animals were used to exclude the influence of
      feeding. Conscious WKY and SHR had a similar UDAV which was lower compared to SD
      rats. Thiopental anesthesia increased UDAV in SHR and WKY but not in SD rats. TDA
      was higher in SHR compared to SD and WKY rats. To investigate the tubular
      capacity to generate DA, the response to L-DOPA infusion was assessed in two
      doses. 1 nmol/min/100 g body weight L-DOPA increased UDAV approximately 30-fold
      in all strains but did not affect tubular sodium excretion or renal hemodynamics.
      In contrast, infusion of 3 micromol/min/100 g body weight L-DOPA increased UDAV
      by five orders of magnitude and induced natriuresis, diuresis, and tachycardia.
      These effects were assigned to an increase in PDA and no significant differences
      were observed among the strains. We conclude that, regarding renal DA, (1) the
      differences among SHR, WKY, and SD rats rather appear to be strain related than
      hypertension associated; (2) the renal capacity of DA generation from L-DOPA is
      not impaired in SHR; (3) tubular DA at physiological concentrations does not
      alter sodium excretion significantly in normo- or hypertensive rats, and (4) the
      influence of anesthesia on UDAV should be considered in comparative studies.

PMID- 9933830
TI  - Long-term effect on blood pressure of early brief treatment by different
      antihypertensive agents: a study in the prague hypertensive rat.
AB  - In the Prague hypertensive rat (PHR), a strain of genetic hypertension derived
      from Wistar, administration of various antihypertensive drugs (AHD) during the
      developmental phase of hypertension (weeks 5-9 of life) prevents the rise of
      blood pressure. However, only drugs blocking the renin-angiotensin system (RAS,
      i.e. AT1-antagonist losartan and ACE inhibitor perindopril) have a long-term
      effect on blood pressure leading to values of systolic blood pressure (SBP) of
      174.5+/-14.5 and 169.8+/-15.3 mmHg, respectively, at week 30. At this time,
      control, untreated PHR have a SBP of 222.0+/-16.6 mmHg (p<0.01 for both groups);
      age-matched PNR (Prague normotensive rat, bred in parallel with PHR from the same
      parent pair) exhibit values as low as 123.3+/-11.7 mmHg (p<0.01 from all other
      values). When losartan was administered to another group of PHR not only at weeks
      5-9 but once more at weeks of 15-19 of age, the values of their SBP at week 30
      were 156.8+/-12.64 mmHg, i.e., values significantly (p<0.01) different not only
      from 239.7+/-17.59 mmHg (value of the untreated PHR group) but also from 174.5+/
      14.5 mmHg (value of PHR to which losartan was administered only once, at weeks 5
      9). Thus, twice repeated administration of losartan in young age almost
      normalizes blood pressure deep into adult age. Proteinuria, a common finding in
      adult PHR, is also significantly lower in adult age in both groups receiving at
      weeks 5-9 drugs blocking RAS; the values at week 30 are 4.0+/-0.26 mg/24 h/rat in
      the losartan and 3.87+/-0.27 in the perindopril group, in contrast to 12.8+/-1.08
      (p<0.01 for both groups) in control PHR. In conclusion, early brief
      administration (weeks 5-9 of life) of RAS-blocking agents to PHR led to long-term
      antihypertensive and antiproteinuric effects. These effects were significantly
      intensified by a second brief administration at weeks 15-19.

PMID- 9933831
TI  - Enalaprilat improves the impaired left ventricular pump function during exercise
      in hypertensives with coronary microangiopathy and with coronary artery disease.
AB  - BACKGROUND: The pump function during exercise can be disturbed not only in
      hypertensives with coronary artery disease (CAD), but also in those with a normal
      angiogram. METHODS: In 10 hypertensive patients (group 1; aged 52+/-4 years, 1
      men, 9 women) with ST segment depression during exercise and concomitant angina
      pectoris but normal coronary angiograms (microangiopathy) and without left
      ventricular hypertrophy (LVMI <110 g/m2), the left ventricular function at rest
      and during exercise was studied by cardiac catheterization and compared with 10
      hypertensives with CAD (group 2; aged 57.6+/-4 years, 7 men, 3 women) and 10
      hypertensives without ST segment depression (group 3; aged 51.8+/-5 years, 10
      men) before and after intravenous administration of 1.25 mg enalaprilat. RESULTS:
      The pulmonary capillary wedge pressure (PCWP) was normal at rest and
      pathologically increased at 60+/-13 W only in groups 1 and 2 (27.2+/-3 and 32.2+/
      8 mm Hg, respectively), but not in group 3 (12.2+/-4 mm Hg; p<0.001). At the
      identical load level, the PCWP in patients with microangiopathy (group 1) was
      significantly (p<0.01) reduced after enalaprilat (-21.7%) and even normalized in
      5 of 10 patients. This was accompanied by a significant (p>0.01) decrease in ST
      segment depression (-73.9%) and in the occurrence of angina pectoris, despite the
      fact that the rate-pressure product as a measure of myocardial oxygen consumption
      was significantly (p<0.05) increased. Also in patients with CAD enalaprilat had a
      significant effect on PCWP (p<0.01), ST segment depression (p<0.01), occurrence
      of angina pectoris (p<0.001), cardiac index (p<0.05), and stroke index (p<0.05)
      during exercise. In group 3 there were no significant changes in PCWP, cardiac
      index, and stroke index after enalaprilat either at rest or during exercise.
      CONCLUSION: The functional improvement under the action of enalaprilat suggests
      that the advantages of the drug may be mediated mainly through an increase in
      myocardial blood flow and that angiotensin II might be involved in the restricted
      increase in coronary blood flow during dynamic exercise in hypertensives with
      coronary microangiopathy.

PMID- 9933833
TI  - Reassessing the role of urodynamics after cerebrovascular accident. Males versus
      females.
AB  - BACKGROUND AND PURPOSE: To determine whether there is a gender difference in the
      need for urodynamics in the evaluation of urinary incontinence after
      cerebrovascular accident (CVA). MATERIALS AND METHODS: We studied 72 consecutive
      post-CVA patients with new onset urinary incontinence documented by the patients
      or the persons who looked after them. Patients were evaluated between 4 and 6
      weeks after their CVA and all had negative urine cultures and a postvoid residual
      urine determination. Exclusion criteria included narrow angle glaucoma, postvoid
      residual urine greater than 100 cm3 and radiographic evidence for a brainstem
      infarct. This left 30 male (mean age 65) and 30 female (mean age 67) patients
      evaluable. Patients were empirically started on anticholinergic medications and
      timed voids for 4 weeks after which cytoscopy and cystometry were performed.
      RESULTS: 28/30 females (93%) reported subjective improvement in their continence
      with conservative measures. 1 (3%) was found to have a urethral diverticulum, and
      1 (3%) had uninhibited detrusor contractions that did not improve with
      medications. In the male group, 20/30 (67%) reported subjective improvement, 5
      (17%) developed elevated postvoid residual urine volumes, 3 (10%) were diagnosed
      with urethral strictures, 1 (3%) had a bladder neck contracture, and 1 (3%) had
      transitional cell carcinoma in situ in the bladder. CONCLUSION: In the patient
      with new onset urinary incontinence in the initial period after CVA, an empiric
      trial of anticholinergic medications and timed voiding may be warranted in a
      select population of female patients without urodynamic testing or cystoscopy.
      This conservative approach may not be appropriate in males because of their
      increased likelihood of having secondary urologic conditions.

PMID- 9933832
TI  - Prejunctional muscarinic receptors modulating acetylcholine release in rabbit
      detrusor smooth muscles.
AB  - We investigated the presence and subtypes of functionally prejunctional receptors
      in cholinergic nerve endings of rabbit detrusor smooth muscle strips using high
      performance liquid chromatography coupled with a microdialysis procedure. The
      effects of pretreatment with various drugs on acetylcholine (ACh) release and
      contractile responses induced by electrical field stimulation were evaluated.
      Although atropine (a muscarinic nonselective antagonist) and 4-DAMP (a muscarinic
      M3 antagonist) did not influence the ACh release, they markedly reduced the
      contractile responses. Pirenzepine (M1 antagonist) decreased ACh release and
      contractile responses. Methoctramine (M2 antagonist) increased the ACh release,
      but did not influence to the contractile responses. These results suggest that
      the muscarinic receptors in the rabbit detrusor smooth muscle are heterogeneous,
      prejunctional facilitatory (M1 receptors), and inhibitory (M2 receptors) for ACh
      release and postjunctional M3 receptors mediating contractile responses.

PMID- 9933835
TI  - Mineral composition of renal stones from the Sudan.
AB  - Urolithiasis is a very frequent finding in the Sudan, but stone analysis is not
      routinely performed in this country. It would, however, give important evidence
      for the metabolic basis of stone formation. We therefore set out to analyze
      urinary stones in 80 Sudanese patients (45 male, 35 female), 12 of whom where
      children. Fourier-transformed infrared spectroscopy was used for stone analysis.
      As is known from other countries, calcium oxalate (CaOx) stones were the most
      frequent, with 68.7% of all stones in adults and 43.7% of childhood stones. Uric
      acid and uric acid dihydrate stones were more often seen in adults (13.2%) than
      in children (4. 1%). Ammonium urate stones are common in the Sudan, especially in
      children (32.9%), which is typical for underdeveloped countries. Infectious
      stones (struvite and carbonate apatite) were more often found in women (7.0%) and
      in children (5.3%) than in men (1.4%). Brushite stones were seldom seen and
      cystine stones did not occur.

PMID- 9933834
TI  - Properties of alpha-1-adrenergic receptors in the rat prostate: effect of
      experimental diabetes.
AB  - We studied the effects of 8 weeks of streptozotocin (STZ)-induced diabetes on the
      density and the pharmacological properties of alpha1-adrenoceptors in the rat
      prostate using receptor-binding experiments with [125I]iodo-2[beta-(4
      hydroxyphenyl)-ethylaminomethyl]tetralone [125I]HEAT. Saturation experiments
      showed the presence of specific [125I]HEAT-binding sites in the control and
      diabetic rat prostate and that the induction of diabetes significantly decreased
      the density of [125I]HEAT-binding sites in the rat prostate. [125I]HEAT-binding
      sites in the prostate of both groups were inhibited by prazosin (nonselective),
      spiperone (alpha1B-selective), WB4101 and 5-methylurapidil (alpha1A-selective)
      and BMY7378 (alpha1D-selective) with the following rank order of Ki values:
      prazosin < WB4101 < 5-methylurapidil < spiperone < BMY7378, indicating a similar
      pharmacological profile of alpha1-adrenoceptor in the 2 groups. Comparing the Ki
      values of the rat prostate with those obtained from the rat submaxillary gland
      (alpha1A), rat spleen (alpha1B), rat vas deferens (alpha1A + alpha1B) and those
      reported for cloned alpha1D, indicates the predominance of the alpha1A + alpha1B
      or the alpha1A subtype in the rat prostate. The present study demonstrates that
      STZ-induced diabetes downregulates the expression of alpha1-adrenoceptor in the
      rat prostate, without significantly affecting the receptor subtype specificity.

PMID- 9933836
TI  - Experience with transurethral incision of ureteroceles.
AB  - OBJECTIVES: The value of primary transurethral ureterocele incision was
      investigated in the treatment of ureteroceles in infants and children. METHODS:
      The charts and radiographic studies of 13 patients between the ages of 2 weeks
      and 8 years who underwent transurethral incision of 14 ureteroceles as primary
      surgical therapy at our institution were reviewed. RESULTS: 57% of the
      ureteroceles were intravesical and 43% extravesical. 64.3% were associated with
      the upper pole of a duplicated system. All 14 ureteroceles were associated with a
      functional renal moiety. Endoscopic incision achieved ureterocele decompression
      in 13 of 14 ureteroceles (93%). Preexisting hydronephrosis improved or resolved
      in 10 of 14 cases (71.4%). Renal function after decompression was not shown to be
      significantly altered or improved. 5 of 13 patients (38%) required definite
      surgical reconstruction for recurrent urinary tract infections, upper pole
      vesicoureteral reflux, hydronephrosis and lower pole vesicoureteral reflux within
      a mean follow-up period of 14 months. CONCLUSION: Transurethral incision has a
      limited role in the treatment of ureteroceles in children. In many or even most
      cases it cannot be expected to constitute long-term definite treatment for
      ureteroceles. It is mainly indicated in patients with urosepsis, prolapsing
      ureteroceles with functional bladder neck obstruction or massive reflux into
      other renal segments. In these settings it reliably achieves decompression and
      allows effective treatment of infection. The function of the previously
      obstructed renal segment can be reevaluated at later point in time to assess
      whether it should be saved. The delay permits interim growth that is likely to
      make bladder reconstruction easier.

PMID- 9933837
TI  - Effects of transurethral prostate resection and transurethral laser prostatectomy
      on plasma hormone levels.
AB  - OBJECTIVE: The short and long-term effects of two common transurethral procedures
      (TURP and TULP, transurethral prostatic resection and laser prostatectomy,
      respectively) on plasma hormone levels in patients with benign prostatic
      hyperplasia (BPH) have been evaluated. PATIENTS AND METHODS: Totally 57 patients
      with histologically proven BPH (age range 54-81 years, mean 62.5 years) were
      included into the study program. Of these 57 patients, 44 underwent TURP and 13
      underwent TULP for treatment of their bladder outlet obstructions. 20 patients
      with bladder cancer undergoing transurethral resection (n = 15) and those
      undergoing transurethral laser ablation (n = 5) constituted the control group.
      Plasma luteinizing hormone (LH), prolactin (PRL), follicle-stimulating hormone
      (FSH), adrenocorticotrophic hormone (ACTH), cortisol, aldosterone,
      dihydroepiandrosterone sulfate (DHEA-S) and testosterone levels were assessed in
      all patients before and after 3 weeks and 3 months following the aforementioned
      procedures. Comparative evaluation of the results with respect to the effect of
      different procedures have been made between study and control groups. RESULTS:
      Preoperatively, we were not able to demonstrate any significant difference with
      respect to all but plasma prolactin levels (p < 0.05) between the study and
      control groups. Prolactin levels were found to be significantly higher in BPH
      patients. In BPH patients undergoing TURP, while LH levels were significantly
      higher during the 3 weeks' evaluation (p < 0.001) no significant difference could
      be shown during the 3 months' examination (p > 0.05). Again, prolactin levels did
      significantly decline (p < 0.05) in patients undergoing TURP during the 3 weeks'
      follow-up evaluation, no difference was present 3 months postprocedure. On the
      other hand, in patients undergoing TULP, while we were not able to show any
      significant difference with respect to plasma prolactin levels (p > 0.05) pre-
      and postoperatively, plasma LH levels were significantly increased during the 3
      month evaluation (p < 0.05). CONCLUSIONS: Alterations in the plasma levels of LH
      and prolactin following prostatectomy during follow-up evaluation, led the
      physicians to consider possible effects of some factors released from resected
      prostate gland. Behavior of prolactin and LH after TURP and laser ablation is
      quite different in our study. It may be related to the higher amount of residual
      prostate tissue after TULP. On the other hand, normalization of hormone levels 3
      months following TURP, led us to think about the activation of some factors
      responsible for hormonal regulation which in turn institutes a new hormonal
      balance.

PMID- 9933838
TI  - Enhanced external counterpulsation as a new treatment modality for patients with
      erectile dysfunction.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive treatment modality
      which can increase arterial blood flow in peripheral and coronary arterial
      disease. Several studies have demonstrated an increase in the flow of the
      internal iliacal artery and in carotid and renal perfusion during EECP treatment.
      We investigated the effect of EECP in patients with erectile dysfunction (ED).
      Thirteen patients were treated with EECP for 20 days, 1 h per day. Patients
      reported a significant improvement of penile rigidity after completion of the
      EECP treatment and a significant improvement of penile peak systolic flow was
      measured by Doppler sonography. No adverse effects were observed. In conclusion,
      EECP seems to be an effective treatment modality in patients with ED.

PMID- 9933839
TI  - Chromophobe cell renal carcinoma.
AB  - Chromophobe cell renal carcinoma is a recently established subtype of renal cell
      carcinoma. Herein we report a case of chromophobe cell renal carcinoma in a 67
      year-old male patient who occasionally underwent computed tomography. In a
      microscopic study with hematoxylin and eosin stain, clear eosinophilic cytoplasm,
      and a moderately atypical nucleus were observed. And it was stained positively by
      Hale's colloidal iron. Ultrastructurally, the cytoplasm was filled with numerous
      microvesicles. From these results, this tumor was pathologically diagnosed as
      chromophobe cell renal carcinoma.

PMID- 9933841
TI  - Scrotal lymphangioma.
AB  - We report a case of scrotal lymphangioma. A 6-year-old boy was referred to our
      hospital due to a right scrotal mass with tenderness. On physical examination the
      mass was discriminated from the testis and showed transillumination. Total
      surgical excision of the mass was performed. The lesion was multicystic, and
      adherent to the skin. Pathological examination revealed lymphangioma. Total
      surgical excision is considered the treatment of choice for this disease.

PMID- 9933840
TI  - A 3,500-gram leiomyoma of the bladder: case report on a 3-year follow-up after
      surgical enucleation.
AB  - We report on a unique-sized large leiomyoma of the bladder wall in a male
      patient. After open surgical intervention all symptoms resolved spontaneously and
      no relapse occurred within a 3-year follow-up period. In conclusion, for
      symptomatic leiomyoma of the bladder surgical intervention should be considered
      as an early treatment option since it is associated with low morbidity, a high
      cure rate for this type of tumor and an immediate relief of urological symptoms.

PMID- 9933842
TI  - Scrotal lymphangioma in children.
AB  - The intrascrotal localization of lymphangioma in children is uncommon, especially
      when the lymphangioma does not depend on testicular structures. We present the
      case of a 13-year-old male who started with a right intrascrotal mass unconnected
      with the testicle, clinically and ultrasonically compatible with cystic
      lymphangioma. The mass was excised because of progressive growth over the
      previous 5 months, and at surgery a scrotal lymphangioma was disclosed projecting
      towards the umbilical area through the subcutaneous cell tissue of the anterior
      abdominal wall. There have been no complications or recurrences to date, 6 months
      afterwards. Surgical removal is the only efficacious therapeutic approach and is
      the best way to achieve a definitive diagnosis in these patients.

PMID- 9933843
TI  - Management of buried penis in adults.
AB  - Buried penis is rarely managed in adults. Two patients with buried penis were
      treated at 18 and 20 years of age. An autolog split-thickness graft was used for
      covering the dermal defect of the penis. Results were successful without any
      evidence of postoperative complications.

PMID- 9933844
TI  - Bilateral cryptorchidism associated with terminal deletion of 10q.
AB  - We report on an infant with terminal deletion of 10q (del10q26.11) presenting
      with bilateral cryptorchidism. Of 9 males previously reported with terminal
      deletion of 10q, 1 had an intersex phenotype, and the others all had combinations
      of cryptorchidism, micropenis, and hypospadias. Terminal deletion of 10q appears
      to include some genes indispensable for normal male genital development.

PMID- 9933845
TI  - A study of growth pattern in giant condyloma acuminatum.
AB  - We report a case of giant condyloma acuminatum (CA) of the perianal region.
      Pathological diagnosis revealed a typical CA with no sign of atypia. In addition,
      HPV type 11 could be identified by Southern blot analysis. PCNA was highly
      positive immunohistochemically, but the positivity of p53 protein was not as high
      as compared with the other control cases. Thus, the high growth rate of tumor
      cells evaluated by PCNA staining seems to contribute to the marked increase in
      size, and not only the p53 mutation but also an other cascade may be implicated
      in cell proliferation.

PMID- 9933846
TI  - Oral calcium supplement decreases urinary oxalate excretion in patients with
      enteric hyperoxaluria.
AB  - We studied the effect of oral calcium supplementation in patients with enteric
      hyperoxaluria. Three patients with renal stone events following ileal resection
      were given oral calcium supplement. One of the three patients was put on a low
      fat diet. The treatment reduced urinary oxalate excretion to the normal range.
      Subsequently, 2 patients reduced the dose of calcium supplementation at their own
      discretion and consequently developed renal stones again together with
      hyperoxaluria. Based on these observations, we believe that an adequate dose of
      calcium can normalize urinary oxalate excretion.

PMID- 9933847
TI  - Parotid metastasis from renal clear cell adenocarcinoma. An unusual site for
      metastasis.
AB  - Metastasis to the parotid region is rare, and originates primarily from head and
      neck squamous cell carcinoma and melanoma of the skin. Renal clear cell
      adenocarcinoma has considerable metastatic potential and the parotid gland is one
      possible destination. Histopathologic study is important to differentiate this
      entity from primary clear cell parotid neoplasm.

PMID- 9933848
TI  - Prevention and management of platelet transfusion refractoriness.
AB  - Platelet transfusion refractoriness is a major complication of long-term platelet
      supportive care. Refractoriness may lead to fatal bleeding complications in
      thrombocytopenic patients. Major factors involved are factors related to the
      clinical condition of the patient as well as HLA alloimmunisation. Non-alloimmune
      factors may occur in up to 80% of the patients. However, platelet transfusion
      outcome is impaired in only 50% of the patients having these conditions. HLA
      alloimmunisation has been convincingly reduced by the use of leucocyte-depleted
      transfusions. UV-B irradiation of platelet transfusions may be alternatively used
      to reduce HLA alloimmunisation. Despite these measures, patients with a history
      of pregnancy or non-leucocyte-depleted transfusions form HLA antibodies in a high
      proportion (up to 50%). HPA antibodies play a minor but relatively important role
      in patients with HLA antibodies. ABO antibodies may play a role in
      refractoriness, which can be abolished by transfusion of ABO-identical platelets.
      Screening for the presence of HLA and/or HPA antibodies is indicated in case of
      transfusion failure after ABO-identical or HLA-matched platelets. If no
      alloantibodies are detected, further analysis to define a role of drug- related
      or autoantibodies is required. In case of HLA and/or HPA alloimmunisation
      associated with refractoriness, matched platelet transfusions are indicated. In
      case of non-alloimmune factors associated with increased platelet consumption,
      increasing the transfusion frequency can be considered. Additional investigations
      are still necessary to define risk factors for secondary HLA alloimmunisation and
      refractoriness due to non-immune factors to further decrease the incidence of
      refractoriness.

PMID- 9933849
TI  - Screening of blood donors for human parvovirus B19 and characterization of the
      results.
AB  - BACKGROUND AND OBJECTIVES: Human parvovirus B19 (B19 virus) can be transmitted
      through blood transfusion and plasma-derived products. In a previous report, we
      utilized the simple hemagglutination method based on the interaction between the
      B19 virus and P antigen on human erythrocytes in order to screen the blood
      donors. We called this method receptor-mediated hemagglutination (RHA) [Lancet
      1995;346:1237-1238]. In this paper, we report on a large-scale screening of the
      B19 virus by RHA and discuss the results. MATERIALS AND METHODS: Donor sera from
      September 1995 to March 1997 and seroconversion panels were enrolled. Donor sera
      were examined by RHA for large-scale screening. The positive sera in the first
      screening were then further investigated by the RHA inhibition test,
      countercurrent immunoelectrophoresis (CIE), an enzyme-linked immunosorbent assay,
      and polymerase chain reaction (PCR). We also evaluated the infectivity and
      neutralizing activity of various kinds of sera by the erythroid colony forming
      unit (CFU-e) assay. To examine the detection limits of the B19 virus by RHA, B19
      viremic sera were purified by sucrose gradient ultracentrifugation. RESULTS:
      Among 257,710 sera specimens, 293 sera (0.11%) gave a positive reaction in the
      first screening using RHA. Out of these 293 sera specimens, 31 were positive for
      PCR, of which 28 were also RHA inhibition-positive, and 25 of the 28 CIE
      positive. In the CFU-e injury assay, all the RHA inhibition (+) sera showed a
      decrease in the number of erythroid colonies. The RHA inhibition (-) PCR (+) B19
      antibody (+) sera did not affect the erythroid colony formation and protected CFU
      e from injury by the B19 virus. By measuring the amount of purified B19 protein
      and its RHA titer, the detection limit of the B19 virus by RHA was calculated to
      the 0.37+/-0.03 ng/ml. CONCLUSION: These results suggest that the RHA(+) RHA
      inhibition (+) sera were infectious in vitro. The combination of RHA and the RHA
      inhibition test is considered to be useful for the large-scale screening of
      infectious B19 virus in blood donors with high specificity.

PMID- 9933850
TI  - Efficiency of leukocyte removal by filters made of superfine glass fiber
      membranes.
AB  - BACKGROUND AND OBJECTIVES: To demonstrate the application of leukocyte removal
      filters made of a new type of filter material - superfine glass fiber - for
      depleting leukocytes in SAGM red cell suspensions and preventing nonhemolytic
      transfusion reactions. MATERIALS AND METHODS: The extent of leukocyte depletion
      and red cell recovery was based on cell counts. Trace leukocytes were counted in
      a 50-microl Nageotte counting chamber or by using a flow cytometer. The chemical
      stability of the glass fiber membranes was studied by plasma emission
      spectrometer and by measuring the ion content and weighing nonvolatile matter in
      water extract. The structural stability of the glass fiber membranes was studied
      by a micropore-filter membrane method. RESULTS: Leukocyte removal filters made of
      superfine glass fiber membranes removed more than 99.0% of leukocytes in SAGM red
      cell suspensions prepared from 400 ml whole blood. Red cell recovery exceeded
      90%, and the total number of residual leukocytes was less than 5x10(6). A water
      extract of the glass fiber membranes contained only traces of Si4+ and Ca2+ and
      less than 2 mg/100 ml of nonvolatile matter. No broken or loose fibers were found
      in the filters. Scanning electron microscopy showed that the web structure of the
      glass fiber membranes was instrumental in trapping and holding leukocytes.
      CONCLUSION: A filter made of glass fiber membranes is effective in leukocyte
      depletion.

PMID- 9933851
TI  - Benefit of prestorage leukocyte depletion of single-donor platelet concentrates.
AB  - BACKGROUND AND OBJECTIVES: The presence of contaminating white blood cells (WBCs)
      in platelet concentrates is associated with transfusion reactions and may
      adversely alter the quality of platelets during storage. Leukocyte depletion by
      filtration of platelets has been increasingly used to avoid these complications.
      However, the best time for filtration and the benefits of filtering single-donor
      platelet concentrates (thrombapheresis, TH) have yet to be clearly defined.
      METHODS: In a randomized study of 202 TH collected with an Autopheresis C system,
      we determined whether prestorage filtration (preSF) of WBCs from TH as compared
      with poststorage (bedside) filtration (postSF) resulted in a better product.
      Levels of cytokines and C3a accumulating in the medium during storage, platelet
      activation state, in vivo platelet recovery, and transfusion reactions were
      compared in pre- and poststorage products. RESULTS: As compared to preSF,
      significantly more postSF TH had detectable levels of tumor necrosis factor-alpha
      (TNF-alpha; 47 vs. 15%; p<0.0001) and interleukin 6 (13 vs. 3%; p = 0.02), lower
      pH (p<0.0001) and decreased levels of C3a (910 vs. 2,000 pg/ml; p<0. 0001).
      Furthermore, platelet activation was increased in postSF TH (p = 0.022). PostSF
      TH tended to plug the bedside filter (27% of postSF TH delivered) from day 3
      onward. There was also a significant difference in platelet recovery, postSF TH
      showing a lower corrected count increment (CCI; p = 0.0055) when taking into
      account the postSF TH that plugged filters (CCI = 0), but no difference when
      plugged TH were excluded. A correlation could be established between TNF-alpha
      levels and poor in vivo recovery (p<0.0001). Febrile nonhemolytic transfusion
      reactions were low in both groups (4 and 9%). CONCLUSION: These results indicate
      a benefit of preSF TH as compared with postSF TH based on the following
      parameters: decrease in cytokine levels, less platelet activation, maintenance of
      higher pH, and more efficient use of stored platelets (27% of postSF TH were lost
      because of plugging of filters). These results apply particularly to the
      Autopheresis C systems with its high initial WBC content.

PMID- 9933853
TI  - Economic impact of donor platelet count and platelet yield in apheresis products:
      relevance for emerging issues in platelet transfusion therapy.
AB  - INTRODUCTION: We analyzed donor platelet counts and platelet product yields in
      708 consecutive platelet aphereses in our program in order to define the
      importance of this relationship for emerging issues in platelet transfusion
      therapy. METHODS: Aphereses performed on the Spectra 3.6 (COBE, Lakewood. Colo.)
      the CS-3000 Plus (Fenwall-Baxter, Deerfield, Ill.) were analyzed. RESULTS: Mean
      platelet count was 237+/-49x10(3)/mm3 (mean +/- SD), and mean yield was 4.24+/-1.
      09x10(11) platelets. Eigthy-five (12%) procedures generated less that 3x10(11)
      platelets. Only thirty-eight (5.4%) procedures yielded >/=6x10(11) platelets, so
      that 'split products' could be obtained. Platelet yields were primarily related
      to the biologic contribution (baseline platelet count) of the donor. Procedure
      parameters selected for harvest, and the efficiency of the device also had a
      significant, but less important role in determining the final platelet yield. An
      increase in mean donor platelet count achieved with Mpl ligand therapy from
      240,000 to 320,000/mm3 would reduce the cost from USD 378 to 267 for each
      apheresis product, since the fraction of split products would exceed 50% of
      apheresis procedures. CONCLUSION: Increasing the donor platelet count would have
      a significant economic impact on platelet apheresis programs, as well as
      important clinical consequences for the role of platelet apheresis products in
      future transfusion strategies.

PMID- 9933852
TI  - Erythropoiesis after therapy with recombinant human erythropoietin: a dose
      response study in anemic cancer surgery patients.
AB  - BACKGROUND AND OBJECTIVES: Preoperative treatment with 600 U/kg of recombinant
      human erythropoietin (r-HuEPO) effectively increases erythropoiesis in cancer
      patients. The aim of this study was to evaluate the erythropoietic response after
      different doses of r-HuEPO in order to find the minimum effective dose. MATERIALS
      AND METHODS: Twenty anemic sideropenic patients (hemoglobin </=110 g/l; serum
      iron <600 microg/l) with cancer of the gastrointestinal tract were randomly
      allocated to two groups: the first (n = 10) received 400 U/kg of r-Hu EPO divided
      in 4 doses (100 U/kg each, every 4 days); the second (n = 10) received 200 U/kg
      of r-HuEPO (50 U/kg each, every 4 days). Both groups were given intravenous iron
      gluconate (125 mg) every day for 15 days. RESULTS: After treatment, the serum
      iron level significantly rose in both groups. The production of new red blood
      cells was 176.3+/-90.8 ml in the 200 U/kg group and 268.4+/-79.4 ml in the 400
      U/kg group (p = 0.036). The increase of hemoglobin was significantly higher in
      the 400 U/kg group (22.3+/-2.0 g/l) than in the 200 U/kg group (14.1+/-2.7 g/l)
      (p = 0.017). CONCLUSION: The r-HuEPO dose of 400 U/kg appears significantly more
      effective than the 200 U/kg to stimulate erythropoiesis in anemic sideropenic
      cancer patients.

PMID- 9933854
TI  - Harvesting of peripheral blood progenitor cells with different programmes of
      discontinuous flow systems.
AB  - BACKGROUND AND OBJECTIVES: From a technical point of view two problems arise
      during the collection of peripheral blood progenitor cells (PBPC): first, the
      volume of the apheresis product is often large, requiring volume reduction prior
      to cryopreservation. Second, the platelet (PLT) loss due to the harvesting of the
      buffy coat is an unwanted side effect. With respect to these problems, the
      present study was designed to compare programs for PBPC collection with
      discontinous-flow cell separators. MATERIALS AND METHODS: Three different
      protocols for PBPC harvesting were investigated in 32 patients with malignancies.
      In the first protocol, the blood cell separator Haemonetics MCS 3p was used. In
      the second protocol using the same machine, the opening and closure of the stem
      cell valve was modified in combination with a centri surge to reduce the PLT
      loss. The MCS+ device with another configuration of the valves was used in the
      third protocol. PBPC were mobilised by chemotherapy plus cytokine administration
      or application of growth factor alone. Blood counts and CD34 antigen-expressing
      cells were determined before apheresis and in the PBPC product. Colony-forming
      unit granulocyte/macrophage (CFU-GM) were determined in the apheresis product.
      RESULTS: 55 PBPC collections were carried out with a median end product volume of
      105 ml. The median counts for CD34+ antigen-expressing cells and CFU-GM were
      1.5x10(6 )and 2.5x10(4)/kg body weight, respectively. PLT loss was significantly
      lower in protocol III. CONCLUSION: The study reported here revealed that PBPC
      could be easily collected in a reduced product volume by the intermittent-flow
      cell separators. No additional centrifugation prior to cryopreservation was
      necessary to remove the plasma from the apheresis product. Patient's PLT loss was
      reduced by the centri surge technique but this still has to be improved.

PMID- 9933855
TI  - Anti-Rh D activity of commercial intravenous immunoglobulin preparations.
AB  - BACKGROUND AND OBJECTIVES: The presence of antibodies against Rh D in intravenous
      immunoglobulin (IVIG) products has been proposed as causing adverse reactions and
      blood grouping problems, although data on the incidence and titre of such
      antibodies is sketchy. This study was conducted to investigate methodology for
      carrying out haemagglutination tests on IVIG products, and to examine in
      retrospect 200 IVIG batches for the presence of anti-D and other haemagglutinins.
      MATERIALS AND METHODS: Batches of commercial IVIG products were tested using the
      low-ionic-strength indirect antiglobulin test (LIAT). Positive batches were
      further investigated using a typed red cell panel and direct haemagglutination
      tests. RESULTS: 44 batches of IVIG gave positive LIAT. Of these, 12 contained
      specific anti-D. 11 batches had LIAT anti-D titres of 2-8; a further batch
      contained anti-D with a LIAT titre of 64. The remaining 32 batches agglutinated
      all erythrocyte phenotypes tested with LIAT titres </=4; 14 of these batches
      showed positive direct haemagglutination and the presence of rouleaux.
      CONCLUSION: 6% of commercial IVIG batches contained specific anti-D, including
      one batch (0.5%) showing unusually high titre. 16% of batches contained
      haemagglutinins of unknown/non-specificity.

PMID- 9933856
TI  - Transfusion-associated graft-versus-host disease in an immunocompetent patient
      following cardiac surgery.
AB  - OBJECTIVES: We determined which of the 22 blood components obtained from
      unrelated donors and transfused to an apparently immunocompetent patient
      following open heart surgery caused transfusion-associated graft-versus-host
      disease (TA-GVHD). METHODS: Serologic and molecular methods were used to type the
      donors, the patient's family members, and the patient's postmortem tissues for
      HLA and a genetic marker on chromosome 17. RESULTS: Two donors were homozygous
      for the HLA class I antigens A1 B8, for which the patient was heterozygous. Both
      donors were heterozygous, not homozygous as expected, for the class II alleles.
      One of them had the same class II alleles as the patient (DRB1*0301,
      DRB3*0101/DRB1*0404, DRB4*0103). The patient's tissues were chimeric for
      restriction fragments at 17p13 of this donor. CONCLUSION: One-way HLA match
      leading to TA-GVHD can be caused by donor blood that is homozygous for class I
      and heterozygous for class II alleles. Two blood components given to our patient
      had such one-way HLA match. Class II alleles of the lymphocytes in one component
      were identical with those of the recipient and caused TA-GVHD. Class II alleles
      of the lymphocytes in the other component differed from those of the recipient
      and were eliminated either by the immune system of the patient or the lymphocytes
      that caused the TA-GVHD (graft versus graft).

PMID- 9933857
TI  - A simple flow-cytometric method for absolute counting of residual white blood
      cells in leukocyte-reduced packed red cells.

PMID- 9933858
TI  - Occupational and Lifestyle Determinants of Blood Lead Levels among Men in Madras,
      India.
AB  - The objective of this epidemiologic study was to assess the relationship of blood
      lead levels to occupational exposure to the combustion products of leaded
      gasoline and to several lifestyle factors (smoking, alcohol consumption, and
      diet) among men from four occupational groups in Madras, India. Blood lead was
      measured using graphite-furnace atomic-absorption spectrophotometry. The mean
      (SD) blood lead levels in 129 blood samples collected from traffic police, bus
      drivers, and auto-shop workers were 11.2 (8.8), 12 (11.1), and 17.5 (8.4) ug/dL,
      respectively; the corresponding value for urban controls (office workers) was 4.1
      (2.1) ug/dL. In a final multivariate regression model, a non-vegetarian diet and
      job category remained the strongest predictors of blood lead level (p < 0.05),
      while smoking, alcohol consumption, and duration of employment were not
      significantly correlated with blood lead levels. The authors conclude that
      continued use of leaded gasoline probably plays a dominant role in determining
      blood lead levels in Madras.

PMID- 9933859
TI  - An Indicator for Assessing Respirable Soot Particles in Diesel Exhaust during
      Occupational Exposures.
AB  - Both acute and chronic impairments of lung function have been demonstrated in
      humans after exposure to diesel exhaust. The concentration of soot particles in
      the diesel exhaust is significantly related to its effects on health. The aim of
      the present analysis was to study the relationship between the concentration of
      respirable dust as an indicator of exposure to soot particles in diesel exhaust
      and a biologic exposure indicator variable, i.e., transient lung function
      decrease. Daily time-weighted average concentrations of carbon monoxide and
      nitrogen dioxide amounted to 9 % and 25% of the applicable hygienic limit values.
      Time-weighted average concentration and the proportion of respirable dust in
      total dust during a workshift were significantly correlated with across-shift
      decreases in lung function. In the absence of a suitable measure for total diesel
      exhaust exposure, the ratio of the proportion of respirable dust in total dust in
      a workplace may serve as an indicator of the concentration of soot particles in
      diesel exhaust.

PMID- 9933860
TI  - Conformity of Workers' and Occupational Health Physicians' Descriptions of
      Working Conditions.
AB  - To determine whether workers, describing their own work, and occupational
      physicians, describing typical workstations, would report the same working
      conditions, and whether the relationships between health status and working
      conditions described by these two sources would be similar. An epidemiologic
      survey was carried out in 1987-88 in 17 poultry slaughterhouses and six canneries
      in France. The data were collected in two ways: workers described their own
      working conditions, and occupational physicians described the working conditions
      at workstations in the same factories. The study included 507 workers who worked
      at fixed workstations that had been described by the 24 occupational physicians.
      Health data were obtained from the workers by the physicians during their annual
      visits. The agreement between workers and physicians in the descriptions of seven
      working conditions was analyzed. On the whole, the prevalences of exposures to
      the seven selected working conditions estimated by the two sources were similar.
      Nevertheless, the observed agreement was not necessarily high. When agreement
      existed about specific working conditions, the relationships observed between
      those conditions and workers' health were generally similar for the two sources.
      This result was stronger for physical health problems than for mental health
      problems. When both sources agreed that the worker was being exposed to a risk
      factor, the risk estimation was higher compared with the cases of discordant
      judgment. This study confirms the usefulness of information provided by experts
      but also the necessity to interview workers themselves about their working
      conditions.

PMID- 9933861
TI  - Stress at Work: An Evaluation of Occupational Stressors as Reported by a
      Multicultural New Zealand Workforce.
AB  - Occupational stress is a cause of considerable morbidity, but research on work
      stressors has comparatively neglected the moderating effects of gender, age,
      ethnicity, and occupation. A workforce of 5,467 European, Maori, Pacific
      Islander, and Asian employees, 40 years old or older, working for 41 companies,
      completed a questionnaire giving details of total stressors and subcategories of
      stressors. Relative risks were estimated using numbers above and below median
      scores. There were significant associations between increased stressors and the
      following [with category showing highest relative risk, and corresponding
      relative risk (95% confidence interval)]: male gender [job scope,
      1.50(1.37,1.63)]; young age [rapport with management, 1.34(11.23,1.46)];
      administrative goup [job pressure, 1.85(1.69,2.03)]; and a negative association
      with Pacific Islander ethnicity [rapport with management, 0.59(0.52,0.66)]. These
      findings indicate areas in a workforce to which stress-reduction interventions
      can be directed.

PMID- 9933862
TI  - Occupational Exposures and Risks of Spontaneous Abortion among Female
      Veterinarians.
AB  - Associations between occupational exposures and spontaneous abortion (SA) in a
      cohort of female veterinarians were studied with pregnancy and job-exposure
      history data collected as part of a mixed-mode survey of all women graduating
      from U.S. veterinary colleges during the 11-year period 1970-1980 (N = 2,997;
      response rate 85.0%). Data analysis focused on SA risks among postgraduation
      pregnancies in relation to 1) type of clinical practice at the time of conception
      and 2) self-reported occupational exposures to 13 exposure entities. Multiple
      logistic regression was used to control for the potentially confounding effects
      of maternal age, gravidity, previous SA, and smoking and drinking behaviors.
      Pregnancies reported by veterinarians employed in all-equine practices were at
      highest relative risk of spontaneous abortion when compared with pregnancies
      reported by unemployed veterinarians [confounder-adjusted odds ratio (aOR) = 2.1;
      95% confidence interval (CI), 0.6-7.4]. Agent-specific relative risk estimates
      ranged from 0.7 to 1.1, suggesting little or no excess risk. However, when
      analyses were restricted to small-animal practitioners, there was a weak
      association between SA risk and job-related exposure to ionizing radiation (aOR
      equals; 1.3; 95% CI, 0.8-2.0), a finding not inconsistent with the results of two
      other studies of female veterinarians. Although this study showed no strong
      associations, the results suggest a relationship between SA among female
      veterinarians and certain exposure types, and thus focus attention on other
      workers who encounter similar on-the-job hazards.

PMID- 9933863
TI  - Exploring the EMF-Melatonin Connection: A Review of the Possible Effects of 50/60
      Hz Electric and Magnetic Fields on Melatonin Secretion.
AB  - This study analyzed the experimental data about the relationship between exposure
      to 50/60-Hz electric and magnetic fields (EMF) and melatonin secretion by the
      pineal gland. The authors report their results and discuss possible health
      consequences, in the light of epidemiologic data suggesting that breast neoplasms
      and depressive disorders might be related to EMF. The nocturnal peak of melatonin
      has been reported to be diminished, or time-shifted, or both, in rodents exposed
      to electric and/or magnetic fields. Current experimental data from primates and
      humans are insufficient to show that this change occurs in them. Epidemiologic
      studies of associations between EMF exposure and breast cancer and between EMF
      exposure and depressive disorders suggest that modifications of melatonin
      secretion could be a biologic signal of these effects. Nonetheless, changes in
      melatonin secretion cannot yet be considered a verified biologic explanation of
      any such association.

PMID- 9933864
TI  - Reproductive Health Hazards in the Workplace: Guidelines for Policy Development
      and Implementation.
AB  - To provide occupational health professionals and employers with guidelines for
      reproductive health policy making, the authors-both of whom are obstetrician
      gynecologists and occupational medicine physicians-review the history of and
      legal basis for U.S. policy on work and reproduction, delineate the goals and
      important elements of a reproductive health policy (RHP), and emphasize the need
      to incorporate an RHP into a comprehensive occupational injury and illness
      prevention program. After suggesting practical ways to achieve the goals of an
      RHP (maximal health protection, compliance with legal mandates, and reduction of
      liability), the authors propose a team-based model for RHP implementation with
      shared responsibility of management and workers in designing, enforcing, and
      evaluating the policy.

PMID- 9933865
TI  - Assessment of Reproductive Risk at Work.
AB  - The risk-assessment process involves hazard identification, dose&endash;response
      assessment, exposure assessment, and characterization of risk. Special competence
      and careful consideration are needed to assess effects on human reproduction.
      There is often a lack of scientific information concerning, e.g., toxic
      influences of chemical substances on human fertility, pregnancy, and offspring.
      Legislation and guidelines concerning workplace exposures need further
      development in many countries. It is important that occupational health and
      safety personnel, as well as experts in this field, assist employers and
      employees in the development of good workplace policies for the protection of the
      reproductive functioning of male and female workers. A protocol for effective
      risk assessment is described.

PMID- 9933866
TI  - Communication Concerning the Risks of Occupational Exposures in Pregnancy.
AB  - The health professional who is involved in communicating information about
      reproductive risks from occupational hazards needs to consider several important
      aspects. Uncertainties in risk assessment, timing of exposure in relation to
      pregnancy, and the consequences of different preventive measures for the woman
      (family), as well as for the employer and other persons at the workplace are
      examples of such aspects. The basis for the pregnant woman's perception of risk
      must be recognized. The risk-communication goal is that the persons concerned
      fully understand the risk and its possible consequences, so that they will be
      able to make informed decisions about how to act. More attention should be given
      to risk communication in the training of health professionals.

PMID- 9933867
TI  - Cardiovascular Risk and Back-disorder Intervention Study of Mass Transit
      Operators.
AB  - A prospective intervention study was conducted to evaluate an employer/union
      sponsored physical and psychological health program, which was offered to 125
      transit operators aged >45 years with >15 years of job seniority. The one-year,
      biweekly program included physical exercise, relaxation, back school, and work
      related stress management and diet counseling. A control group (n = 26) was
      available for comparison. Twenty-seven operators dropped out of the study. WHO
      cardiovascular risk survey methods, ergometry, Minnesota ECG coding, standardized
      low-back tests, blood lipids, lead, and carboxyhemoglobin were measured. Before
      the intervention, the ten-year cardiovascular-disease risk of all study subjects
      (15.1%) was greater than that of the general reference population (14.0%). After
      the intervention it fell to 12.9%, but not significantly compared with that of a
      non-exercising control group, which also showed a reduction. The prevalence and
      the self-rated intensity of back problems were reduced after the intervention:
      55.4% of low-back-pain sufferers reported substantial improvement, and only 12.3%
      reported substantial worsening. The multidisciplinary intervention program
      appeared to be effective for musculoskeletal conditions, but not for overall
      cardiovascular risk, compared with the controls.

PMID- 9933868
TI  - Comparison of Two Questionnaires on Respiratory Symptoms in a Nicaraguan
      Population: Value in Diagnosis of Chronic Bronchitis.
AB  - Two questionnaires about respiratory symptoms were evaluated for reliability and
      ability to diagnose chronic bronchitis in a study population of 129 Nicaraguans
      (110 workers and 19 patients with chronic bronchitis). The first questionnaire
      (AQ) had symptom questions that were based on British Medical Research Council
      (MRC) questions, adapted to local Spanish. The second questionnaire (MRCQ)
      contained MRC symptom questions translated directly into Spanish. The reliability
      of the questions was measured in a test-retest procedure. The questionnaire-based
      diagnosis of chronic bronchitis was compared with the diagnosis made by a
      physician (for workers) or from the hospital records (for patients). The
      questions concerning symptoms in both questionnaires were of acceptable
      reliability. For the diagnosis of chronic bronchitis in workers, the AQ showed
      similar sensitivity, a somewhat higher specificity, and a substantially higher
      positive predictive value (90%) than the MRCQ (57%). Among the patients, the AQ
      identified 17 patients as positive (sensitivity 89%), while the MRCQ identified
      15 (sensitivity 79%). respiratory questionnaire; reliability; chronic bronchitis;
      Nicaragua Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996
      April/June Chronic Exposure to Cigarette Smoke Inhibits the Stimulating Effects
      of Mineral Fibers on the Production of Tumor Necrosis Factor by Alveolar
      Macrophages of Rats 95 98 EN Yasuo Morimoto Department of Environmental Health
      Engineering, University of Occupational and Environmental Health, Japan 1-1,
      Iseigaoka, Yahatanishiku, Kitakyushu 807, Japan. Ziro Nambu Hajime Hori Tohru
      Tsuda Hiroshi Yamato Toshiaki Higashi Yasuyuki Yokosaki Masamitsu Kido Isamu
      Tanaka The objective of this study was to evaluate the chronic combined effects
      of mineral fibers and cigarette smoke on the production of tumor necrosis factor
      (TNF) by alveolar macrophages. The authors chronically exposed ten rats to
      cigarette smoke in vivo and measured the production of TNF by alveolar
      macrophages in the presence of mineral fibers in vitro. For smoke exposure, rats
      were divided into two groups. Five rats were exposed daily to a concentration of
      10 mg/m(3) of cigarette smoke for six hours a day, five days a week, for four
      weeks, and five rats (control) were not exposed to smoke. A broncho-alveolar
      lavage was performed after the smoke exposure, and the recovered alveolar
      macrophages were incubated with either chrysotile or ceramic fibers on a
      microplate for 24 hours. TNF activity in the supernatant was determined by the
      L929 bioassay. When alveolar macrophages were not stimulated by mineral fibers,
      TNF production tended to be lower in smoke-exposed alveolar macrophages than in
      unexposed ones, although the difference was not significant statistically. When
      alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibers,
      both fibers stimulated TNF production, but TNF production in smoke-exposed
      alveolar macrophages was lower than that in unexposed macrophages. These results
      revealed that long-term exposure to cigarette smoke inhibited the stimulating
      effect of mineral fibers on the production of TNF.

PMID- 9933869
TI  - ISO 14000: Origin, Structure, and Potential Barriers to Implementation.
AB  - The ISO 14000 is likely to become the international standard for environmental
      management. At present, it is an evolving series of individual voluntary
      standards and guideline reference documents that provide business management with
      the structure for managing environmental impacts. These encompass environmental
      management systems, environmental audits, eco-labeling, environmental performance
      evaluations, life-cycle assessment, and environmental aspects in product
      standards. The authors present the rationale for the ISO 14000 and the steps in
      its evolution so far, as well as its present provisions and their implications
      and its position with regard to regulatory agencies. Particular attention is paid
      to the consequences of voluntary disclosure and correction of violations. Hanley
      & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June
      Perspectives on Rural Environmental Health in Central Europe 125 134 EN Tomas
      Trnovec Burton C. Kross CIREH-Room 352, International Center, University of Iowa,
      Iowa City, IA 52242, USA. Emil Ginter Life expectancy is about five to seven
      years less in Central European countries than in comparable countries in Western
      Europe. Environmental and occupational health risk factors, along with the
      socioeconomic and political conditions that have prevailed in this region for the
      past 40 years, are suspected contributing factors to this condition. The initial
      impression among observers was that environmental pollution by industry was the
      primary source of contamination leading to human health effects. Current thinking
      by the authors recognizes that combinations of personal habits, local
      environmental emissions (home heating), and occupational risk factors are more
      likely to be influencing the health of this region, particularly in rural areas.
      A predictive model for standard mortality rates determined that only three
      potential risk factors were statistically significant: consumption of alcoholic
      beverages, consumption of citrus fruits, and consumption of cereals. Additional
      emphasis should be placed on defining risk factors in rural areas of Central
      Europe, and designing intervention strategies to address these factors.

PMID- 9933870
TI  - Environmental Exposure to Organic Mercury among the Makuxi in the Amazon Basin.
AB  - Gold mining in the savannah region of northern Brazil (Roraima) has increased
      dramatically since 1989. Elemental mercury is used to extract gold from sediment.
      Mercury released into the Amazon aquatic ecosystem may convert into the organic
      form and bioconcentrate in the food chain, posing a hazard for fish-eating
      peoples such as some of the Makuxi. This survey compared blood organic mercury
      levels among Makuxi villagers along mined (Rio Cotingo) and unmined (Rio Surumu)
      rivers. Seventy-five blood samples were obtained from villagers who did not
      participate in gold mining or processing procedures in three Makuxi villages:
      Maravilha (heavily exposed), Limao (limitedly exposed), and Matarucca (minimally
      exposed). Blood was analyzed for total and inorganic mercury content by cold
      vapor spectrophotometry. Mean blood organic mercury levels among the villagers of
      Maravilha, Limao, and Matarucca were 31.3 mg/L, 9.3 mg/L, and 2.0 mg/L,
      respectively (p = 0.001). The authors conclude the gold mining process is
      contaminating the environment of Roraima and may pose a health hazard to its fish
      eating populations, such as the Makuxi people.

PMID- 9933871
TI  - Occupational and Environmental Risk Factors for Asthma in Rural Communities in
      China.
AB  - Respiratory allergens such as dust, gases/fumes, and hay smoke, which are
      frequently present in agricultural settings, can cause or aggravate asthma. The
      purpose of this study was to examine the relationships between occupational and
      environmental exposures and asthma in Chinese rural communities. The study
      population consisted of 28,946 people 15 years old or older, living in rural
      areas of Anhui province, China. A modified Mandarin translation of the ATS-DLD
      questionnaire was administered by trained interviewers to request information
      about exposures to specific occupational/environmental agents and respiratory
      disorders. In Huaining, the prevalence of wheezing was 3.8% for men; 2.1% for
      women; the prevalence of asthma was 1.6% for men; 1.8% for women. In Zongyang,
      the prevalence of wheezing was 2.7% for men; 1.9% for women; the prevalence of
      asthma was 1.7% for men; 1.2% for women. With control for potential confounders
      such as gender, age, residential area, education level, and smoking status, the
      pooled adjusted odds ratios (ORs) of wheezing and asthma for the group exposed to
      wood/hay smoke were 1.36 (95% CI: 1.14-1.61) and 1.27 (95% CI: 1.02-1.58),
      respectively. For coal-stove users, the pooled adjusted ORs were 1.47 (95% CI:
      1.09-1.98) for wheezing and 1.51 (95% CI: 1.05-2.17) for asthma. After
      stratification of the subjects by dust type, the estimated ORs for wheezing were
      1.58 (95% CI: 1.02-2.44) among the group exposed to inorganic dust and 3.03 (95%
      CI: 1.25-7.33) among the group exposed to metal dust. Asthma was not shown to be
      significantly associated with any specific dust type. Findings of the present
      study are consistent with previously reported adverse respiratory health effects
      related to occupational/environmental exposures to wood/hay smoke and dust, and
      indicate the need for further occupational disease surveillance in rural
      communities.

PMID- 9933872
TI  - Upper-limb Postures and Movements during Diamond Polishing.
AB  - Previous occupational health studies of diamond polishers have identified high
      rates of musculoskeletal disorders of the hands and arms in this population,
      specifically, ulnar neuropathy in the right elbow. These disorders may be due to
      the repetitive and forceful motions of the upper extremity required to manipulate
      the hand-held polishing tools. A video-based, biomechanical analysis of the upper
      extremities of polishers at several diamond-processing factories in Israel was
      conducted. Detailed motion measurements of the wrists, elbows, and shoulders of
      polishers were made while the subjects performed their usual work. During a
      typical workday, the basic polishing cycle, which involves a series of
      stereotyped hand and arm movements, is repeated more than 5,000 times. Sustained,
      extreme flexion of the right elbow, which is the arm holding the eyepiece, may
      account for the higher rates of ulnar neuropathy in this extremity.

PMID- 9933873
TI  - Musculoskeletal Symptoms among Computer-assisted Design (CAD) Operators and
      Evaluation of a Self-assessment Questionnaire.
AB  - A self-administered questionnaire with questions related to the physical workload
      at video display units (VDUs) was tested for intra- and intermethod reliability
      among 36 men and 64 women working with research and documentation. The results
      showed an acceptable test-retest agreement. The answers to three questions were
      validated by direct measurements: the locations of keyboard and mouse on the
      table, and the distance between elbow and keyboard heights when working. The self
      reported locations of keyboard and mouse showed good agreement with the direct
      measurements. A revised version of the questionnaire was used at a
      telecommunication laboratory to study work postures and musculoskeletal symptoms.
      Among CAD operators with identical work tasks, the women (n = 67) reported a
      higher prevalence of musculoskeletal symptoms than did the men (n = 475).
      Calculated prevalence rate ratios (women/men) for musculoskeletal symptoms ranged
      from 1.4 (low back) to 3.4 (left elbow). The CAD operators with at least 5.6
      hours of mouse use/week (median) reported more symptoms in the arms than did the
      CAD operators with fewer hours' work. Operators with the mouse located outside an
      "optimal" area on the table reported more symptoms from shoulder joints (upper
      arms), shoulders (scapular), elbows, and wrists than did operators with the
      optimal mouse location. Thus, long hours of work with the mouse, as well as
      working with the mouse non-optimally located on the table, seemed to be risk
      factors for upper-limb symptoms.

PMID- 9933874
TI  - Spontaneous Abortions of Known Karyotype Related to Occupational and
      Environmental Factors: A Case-Referent Study.
AB  - The aim of the study was to examine the roles of occupational and environmental
      factors in relation to spontaneous abortions with known karyotypes. A case
      referent study was performed among 793 women hospitalized for spontaneous
      abortion and 808 referents attending ultrasound screening at 17-18 weeks of
      pregnancy. Chromosomal analysis were obtained for 371 abortuses and 679 referent
      newborns. Significantly elevated odds ratios (ORs) for abortions with abnormal
      chromosomes were found for maternal psychological strain at work (OR:1.8),
      exposure to anesthetic gases (OR:6.9), video display unit work >/= 1/2 working
      day (OR:1.9), and sales work (OR:2.0). An association with paternal security work
      (OR:3.0) was possibly confounded by maternal exposure to psychological strain.
      Abortuses with normal chromosomes were associated with maternal sales work
      (OR:1.9) and psychological (OR:2.3) and physical (OR:1.6) strain at home, and
      with paternal construction work (OR:2.1) and physical strain at home (OR:1.9). No
      relationship between air pollution and spontaneous abortion was observed
      regardless of karyotype.

PMID- 9933875
TI  - Lung Function in Woodworking Teachers in Sweden.
AB  - Work-related airways symptoms are common in woodworkers. To study possible work
      related effects on lung function, 40 exposed woodworking teachers and 31 controls
      were examined by spirometry, diffusion-capacity and nitrogen-washout
      determinations, and methacholine challenge. Measured levels of total and
      respirable dust and terpene concentrations in the shops were below the Swedish
      threshold-limit values. Lung-function values on Monday morning were similar in
      the two groups. Slight obstructive impairments during the working week were found
      in both groups. In the woodworking teachers, small changes in lung function were
      related to measured total dust, use of process ventilation, and use of a broom to
      clean the benches. Their methacholine reactivity was slightly more pronounced
      compared with that of the controls, but the numbers of hyperreactive individuals
      (PC&inf20; < 8 mg/m(3)) were equal in the two groups. These facts might indicate
      small work-related effects on lung function, but some contradictory findings
      disturb this interpretation. The results are therefore inconclusive.

PMID- 9933876
TI  - An Economic Analysis of Water and Sanitation Infrastructure Improvements in the
      Colonias of El Paso County, Texas.
AB  - The authors conducted a cost-benefit analysis of a project to improve water
      supply and sanitation infrastructure in a rural community (colonia) along the
      United States-Mexico border. The present value of total costs in the scenario
      without improvements was $42,937,507, compared with net costs with improvements
      of $34,600,800. It is estimated that improved access to safe drinking water and
      solid waste sanitation prevented 155 cases of hepatitis A and 5,165 cases of
      gastrointestinal illness over 26 years and saved $846,541 in associated health
      care costs, approximately 10% of the total estimated savings. The majority of
      benefits was in the form of time savings and increased land values. The authors
      did not consider the value of improving environmental conditions for future
      generations and preventing communicable disease epidemics associated with poor
      sanitation. Accurate value estimates for these benefits might strengthen the
      argument for undertaking similar infrastructure-improvement projects in the
      colonias and in other underdeveloped rural areas of the United States. cost
      benefit analysis; water supply and sanitation; health care costs; disease
      prevention effectiveness Hanley & Belfus, Inc. Int J Occup Environ Health 1077
      3525 2 3 1996 July/September Decreases in Subpopulations of T Lymphocytes and
      Natural Killer Cells in the Blood of Retired Chromate Workers 222 225 EN Takeshi
      Tanigawa Shunichi Araki Department of Public Health, Faculty of Medicine,
      University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Akinori Nakata
      Takaharu Araki Susumu Sakurai To examine the effects of past exposure to
      chromates on lymphocyte subpopulations in man, the authors measured
      subpopulations of T lymphocytes and natural killer (NK) cells by flow cytometry
      together with B lymphocytes in blood samples from 27 male workers and 22 healthy
      controls. All subjects were nonsmokers. The numbers of CD4+CD45RA+ (suppressor
      inducer), CD8+ (suppressor/cytotoxic) and total T lymphocytes, CD16+CD57+ NK
      cells, and total lymphocytes in the blood of chromate workers were significantly
      smaller than those in the blood of healthy controls (analysis of covariance with
      age as a covariate). It is suggested that suppressor-inducer and
      suppressor/cytotoxic T lymphocytes and NK cells with intermediate NK cell
      activity are most susceptible to the effects of past exposure to chromates as
      compared with other lymphocyte subpopulations such as B and CD4+CD29+ T
      lymphocytes.

PMID- 9933877
TI  - Magnetic-field Exposures in the Workplace: Reference Distribution and Exposures
      in Occupational Groups.
AB  - Exposures to extremely-low-frequency magnetic fields were assessed by taking
      personal measurements with a dosimeter calibrated at 50 Hz with a bandwidth of 40
      400 Hz. The study group was a population-based random sample of 1,098 Swedish
      men. Exposures were determined as workday mean, median, maximum, and standard
      deviation, and the time fraction of the day when exposures exceeded 0.20 uT. For
      workday means, the 50th percentile was 0.17 uT, and the 75th percentile was 0.27
      uT. For median values, the 50th percentile was 0.11 uT and the 75th percentile
      was 0.16 uT. The strongest correlation (Spearman rank correlation = r&infs;)
      found was between the workday mean and the fraction of time above 0.20 uT
      (r&infs; = 0.89). The authors used the same data to estimate exposures for the
      100 most common occupations according to the 1990 Swedish census. A minimum of
      four independent measurements for each occupation was required. Among occupations
      with low workday mean values were earth-moving machine operator, health care
      worker, and concrete worker. Among occupations with high workday mean exposures
      were welder and electrical or electronics engineer or technician. High exposure
      levels were also found in occupations outside the study base, such as train
      engine driver and glass, ceramic, or brick worker. Exposures to magnetic fields
      vary widely, since levels of exposure are strongly affected by factors such as
      duration of exposure and distance from the source. Large variations often found
      between individuals within occupations could reflect variations in tasks across
      different workdays for the particular occupations and/or local conditions such as
      tools and installations, and/or how the work is organized and performed.

PMID- 9933878
TI  - Musculoskeletal Disorders: Work-related Risk Factors and Prevention.
AB  - Work-related musculoskeletal disorders cause chronic pain and functional
      impairment, impose heavy costs on society, and reduce productivity. In this
      position paper from the Scientific Committee for Musculoskeletal Disorders of the
      ICOH, the most important risk factors at work are described. Work-related
      musculoskeletal disorders have high incidences and prevalences among workers who
      are exposed to manual handling, repetitive and static work, vibrations, and poor
      psychological and social conditions. The application of ergonomic principles in
      the workplace is the best method for prevention. International organizations
      should develop standards, common classifications, and terminologies. Surveillance
      systems should be further developed nationally and in workplaces, and more effort
      should be directed to information dissemination, education, and training.

PMID- 9933879
TI  - Determinants of Economic Cost Related to Low Back Pain among Nurses at a
      University Hospital.
AB  - The objectives of this study were to determine the economic cost related to low
      back pain (LBP) among nurses, and to identify factors associated with this cost.
      All 998 nurses at the National Taiwan University Hospital (NTUH) were asked to
      complete a questionnaire designed to examine whether the nurses had experienced
      LBP and whether their LBP had been related to the incurring of economic cost
      between May 1, 1990, and April 30, 1991. Of the 863 respondents, 417 had had LBP
      and 102 of these had incurred economic costs related to the LBP. Personal
      interviews of the 102 nurses, as well as of an additional four nurses who had
      resigned due to LBP within the 12 months, were performed to determine the related
      economic costs. The total monthly costs over the 12 months ranged from U.S.
      $105,405 to $149,083. Twenty percent of the 106 cases were responsible for 70% of
      the total overall cost. There was no difference in demographics between the two
      groups of non-LBP and LBP-without-cost. However, statistical analysis using
      logistic regression showed that the occurrence of economic cost was positively
      associated with subjective pain, lifting and carrying babies and small children
      at home, and age or work years or parity. In addition, multiple linear regression
      analysis showed that medical cost was positively associated with parity and sick
      leave; and productivity loss was associated with sick leave, lifting and carrying
      babies at home, unspecified housework, patient transport, and performing
      cardiopulmonary resuscitation.

PMID- 9933880
TI  - Reduction of Acute Low Back Injuries by Use of Back Supports.
AB  - The objective of this study was to determine the effect of a change in back
      support-use policy on the occurrence of work-related low back injuries among a
      large cohort of employees in the retail-trade home improvement industry. Working
      hours of exposure, back support use, and intensity of materials-lifting
      requirements were collected from 1989 through 1994. Records of injury-related
      claims were reviewed for all documented injuries to the lower back among members
      of the cohort during the same period. Over 101,000,000 working hours were
      recorded by nearly 36,000 employees; 2,152 employees reported an acute low back
      injury occurring during working hours as a first report of episode, with medical
      physician diagnosis and acute/abrupt onset. Incidence density rates were
      calculated for persons wearing and not wearing the back support. Rate ratios and
      prevented fractions were evaluated. Before implementation of a company-wide back
      support policy, the employees had a rate of acute low back injuries of 30.6 per
      million working hours. After implementation, this rate fell to 20.2 per million
      working hours, a significant reduction of 34.0%. This effect was seen in both
      genders, in younger workers and in those aged 55+, with low levels of lifting as
      well as high lifting intensities, and in persons with one to two years of
      employment with the company. The authors conclude that uniform mandatory
      implementation of a back-support-use policy significantly reduces the incidence
      of acute low back injuries incurred in the workplace.

PMID- 9933881
TI  - Burnout among Nurses in the People's Republic of China.
AB  - This study was designed to examine the burnout symptoms among nurses in different
      settings, differing by specialty, age, gender, number of years on the job, and
      place of work, in the People's Republic of China. A total of 1,100 nurses
      completed the Maslach Burnout Inventory. Burnout symptoms in nurses were related
      to setting, specialty, age, gender, place of work, and number of years on the
      job. The findings suggest that the physical features in clinics and in obstetrics
      and gynecology departments should be improved and that social and public health
      support systems, as well as stress management skills, should be offered to new
      nurses in order to improve their ability to cope with stress and to improve the
      quality of care for patients.

PMID- 9933882
TI  - Paternal Occupational Lead Exposure and Pregnancy Outcome.
AB  - Self-reported reproductive histories of male employees of a lead-zinc smelter
      were related to pre-conception measures of lead exposure to examine associations
      between paternal occupational lead exposure and adverse pregnancy outcome. The
      participants reported 2,021 pregnancies which resulted in 1,684 normal live
      births, 12 stillbirths, 30 birth defects, 203 spontaneous abortions, and 92
      "other" outcomes. Birth defects and stillbirths were combined for the analysis.
      The risk of a stillbirth or birth defect was elevated for pre-conception
      employment in a high-lead-exposure compared with a low-lead-exposure job (odds
      ratio = 2.7, 95% confidence interval = 0.7, 9.6). A similar risk was found for
      pre-conception blood lead levels of 25-39 ug/dL and >/= 40 ug/dL when compared
      with blood lead levels of < 25 ug/dL (OR = 2.9, 95% CI = 0.6, 13.3, and OR = 2.5,
      95% CI = 0.5, 11.6, respectively). No association was found between pre
      conception lead exposure and spontaneous abortion. A relatively low response rate
      to the questionnaire and potentially erroneous reporting of reproductive outcomes
      by male workers are limitations of the study.

PMID- 9933883
TI  - Screening and Neuropsychological Assessment of Spray Painters at Risk for Organic
      Solvent Neurotoxicity.
AB  - The aim of this study was twofold: 1) To examine the usefulness of the screening
      Questionnaire 16 (Q16) in relation to Type 2 organic solvent neurotoxicity (OSN).
      Type 2 OSN is defined by chronic exposure to neurotoxic solvents and symptoms of
      neurotoxocity, and is divided into Type 2A, characterized by sustained
      personality or mood change, and Type 2B, characterized by impairment in
      intellectual function. 2) To determine the sensitivities of a number of
      neuropsychological tests in the assessment of OSN. Subjects of the study were 20
      spray painters with high Q16 scores and two control groups-20 spray painters with
      low Q16 scores, and ten nonexposed panel beaters (aged 23-53 years). The subjects
      were given psychological and neuropsychological assessments by a psychologist
      blind to their Q16 status. Seven of the 20 men with high Q16 scores had
      significant numbers of both neuropsychological and psychological symptoms, with
      an additional four having small numbers of cognitive symptoms only. Men who had
      low Q16 scores did not have enough symptoms to indicate clear OSN, although eight
      men in this group had small numbers of depressed neuropsychological test scores.
      A MANOVA on individual tests demonstrated that single tests failed to
      discriminate the groups at the 0.05 level. The results suggest that the Q16
      effectively screens men with clear Type 2 OSN, most of whom have both
      psychological and neuropsychological symptoms. It is less reliable for screening
      men with few neuropsychological deficits. Those tests most sensitive to the
      neuropsychological symptoms of OSN are Digit Symbol, the Rey Osterreith Complex
      Figure, and the California Verbal Learning Test. The results of the study do not
      provide strong support for the division of Type 2 OSN into Type 2A and Type 2B
      OSN.

PMID- 9933884
TI  - Paraquat Exposure of Knapsack Spray Operators on Banana Plantations in Costa
      Rica.
AB  - A study of occupational exposure to paraquat was performed among 11 knapsack
      spray operators at banana plantations in Costa Rica. External and internal
      exposures were quantified and determinants of exposure identified by
      measurements, observations, and interviews. Dermal exposure was measured with
      skin pads, respiratory exposure by personal air sampling, and internal exposure
      by urine sampling. The wrists, back, and legs were the areas with the highest
      levels of dermal exposure. Respiratory exposures appeared to be strongly
      influenced by differences between days, while dermal exposures varied mostly due
      to differences between plantations. The use of protective clothing did not
      effectively protect against dermal exposures. Both respiratory and dermal
      exposures were significantly related to internal exposures, and both should be
      considered possible routes for systemic absorption of paraquat. It cannot be
      excluded that measurable levels of exposure can lead to acute as well as chronic
      health effects. Furthermore, due to poor conditions within the working
      environment, the spray operators are continuously at risk for high exposures that
      could lead to severe intoxication, and therefore a strategy for control of
      exposure is necessary.

PMID- 9933885
TI  - A Regional Occupational Medicine Service: Qualitative and Quantitative
      Assessment.
AB  - A quantitative description of a regional occupational medicine system, serving
      some 200,000 workers in a broad spectrum of occupations, is given. The main
      activities of the service-pre-employment, medical surveillance, and fitness-to
      work examinations-are presented in quantitative terms. Approximately 27,000
      examinations are performed annually, of which about 50% require biological
      monitoring for a specific occupational exposure, 35% are fitness-for-work
      examinations, and 15% are pre-employment examinations. The main abnormal findings
      identified by fitness examinations involved the musculoskeletal (25%),
      cardiovascular (13%), or upper respiratory, pulmonary, and neurologic systems (3%
      each). Among surveillance examinations, the most frequently identified pathology
      is phonal trauma (11%). The three types of examinations are looked at with
      respect to rates of abnormal findings over a one-year period, compared with the
      mean rate of abnormal findings over the preceding five-year period, and future
      trends are extrapolated. The implications regarding assessment of resource
      allocation, appropriate budgeting, and personnel recruitment and training, as
      well as planning of worker safety and health maintenance programs, are noted. The
      authors conclude that ongoing quantitative analysis of the activities of a
      regional occupational medicine service is mandatory for quality assurance and
      future planning responsive to the dynamic needs of the target workforce.

PMID- 9933886
TI  - Industrial Counseling: Linking Occupational and Environmental Health in Tanneries
      of Kanpur, India.
AB  - This paper describes an occupational health program in tanneries in Kanpur,
      India. The program was instituted as part of a bilateral cooperative effort of
      India and The Netherlands focusing on providing engineering solutions to prevent
      industrial waste and community sewage from polluting the Ganges river. The
      occupational health program was linked to the environmental activities by
      adopting the concept of industrial counseling. This method aims to increase
      production and product quality of enterprises and at the same time improve
      working conditions in these enterprises. The tanneries in Kanpur were targeted
      for industrial counseling by the Indo-Dutch Environmental and Sanitary
      Engineering Project Kanpur- Mirzapur under the Ganga Action Plan. Recovery of
      chrome from wastewater, automation of hydraulic press machines, use of an air
      pollution-prevention system in the spray-painting section, and automation of
      transport are examples of measures used to increase productivity and improve
      leather quality. Working conditions were improved by adding local exhaust
      ventilation, mechanizing material transfer, instituting safer procedures for
      storage and use of toxic materials, and introducing breathing apparatus for
      operations done in confined spaces to prevent hydrogen sulfide intoxication. The
      linkage of occupational health problems to environmental issues proved to be
      effective in drawing attention to working conditions. Also, the application of
      simple survey techniques to identify and evaluate environmental and occupational
      hazards substantially increased awareness of these hazards and comprehension of
      the need to adopt changes among employers, workers, and occupational health
      professionals. The article discusses the core elements of this successful
      program.

PMID- 9933887
TI  - Appraisal of Risk Perception in Occupational Health and Safety Research in
      Developing Countries.
AB  - This paper addresses scientists in the field of occupational health and safety,
      with a special emphasis on research in developing countries. The article is based
      on findings of and a method used in a recent study of occupational health and
      safety in mines in Africa and Latin America. Dialog between technical experts and
      social scientists is needed to synthesize the values of society and the facts of
      nature into policy decisions that are both politically legitimate and consistent
      with the current state of technical knowledge. The author asks how researchers in
      the field of occupational health can take two axioms of the social sciences into
      account: 1) the concept of human agency, and 2) the notion that risk perception
      is socially constructed: rather than being determined by "real" risks, it is
      shaped by the adversarial context of, among other factors, the nature of labor
      relations, values in society, and personal histories. With regard to first axiom,
      it is shown why actors' risk perceptions and their context need indeed to be
      taken seriously. With regard to the second, a methodologic outline is given to
      complement technical research on occupational hygiene with risk-perception
      appraisal. The method is actor-oriented, building on the perceptions, views, and
      opinions of the different groups of relevant actors. Systematic integration of
      this method into technological studies could enrich them, contributing
      substantially to their applicability.

PMID- 9933888
TI  - Teaching history of medicine in the perspective of "medical humanities".
AB  - The current interest in philosophical questions and ethical aspects of medicine
      turns attention towards the past and obtains suggestions and perspectives from
      previous descriptions and interpretations of sickness, therapy, and the relation
      between the patient and physician. Culture as therapy and therapy as culture are
      fundamental challenges for the present; physician, patient, and society, i.e.,
      humans and humane medicine, need this dialogue, which should also be constitutive
      for teaching history of medicine. Through the separation of the natural sciences
      and the humanities, modern progress of medicine has produced many benefits but
      has, at the same time, raised many problems. Negative consequences of this
      development exist not only for the patient, but also for his personal environment
      and for the physician. In the course of modern history, there have been several
      reactions aimed at overcoming these one-sided tendencies: in the Renaissance, in
      the epoch of Romanticism and Idealism, and at the beginning and the end of the
      19th century. This article outlines, with historical examples and contemporary
      reflections, the concept of teaching history of medicine in the perspective of
      "medical humanities".

PMID- 9933889
TI  - Importance of philosophy of science to the history of medical thinking.
AB  - Popular approach to the history of medicine rests on naive assumptions that: 1)
      only the present state of medical knowledge can be counted as scientific and only
      those elements of the former knowledge and practice which fitted the body of
      contemporary science should be regarded by the historians of medicine
      (presentism); 2) medical sciences, like the other natural sciences, portray
      natural phenomena as they really are (naturalism); 3) progress in sciences
      consists of cumulative growth of information and explanation. The twentieth
      century philosophical critique of science revealed that none of these assumptions
      were true. Empirical facts, which are taken as a basis for any true knowledge,
      are dependent on the presumed theories; theories are intertwined into a broader
      socio-cultural context; theory-changing processes are caused by social factors
      rather than by the theoretical content. Therefore, it is a common task of
      historians of medicine and philosophers of science to reveal all theoretical and
      cultural premises on which our comprehension of the contemporary medicine is
      founded.

PMID- 9933890
TI  - Role of history and philosophy of medicine in the professional formation of a
      physician: writings of Polish school of philosophy of medicine.
AB  - Polish physicians-philosophers tried to find a compromise between medicine as a
      science and medicine as a healing art. They stated that clinical practice should
      be transformed into science, bearing in mind that there would be no medicine
      without the existence of the sick. A perfect physician is a good and wise person
      and not exclusively a proficient expert. Polish physicians exercised a science
      that they called philosophy of medicine. It included logic, psychology, and
      medical ethics. The Polish school claimed that the history of medicine and
      philosophy of medicine are necessary for future doctors. The historical and
      philosophical approach makes it possible to recognize the subject of medicine
      (health, disease, and the sick) and its aim (treatment, restoration of health or
      just alleviation of suffering). The ethics teaches what values are pursued by
      medicine, what moral duties a doctor has, and what role model to follow to become
      a good physician. Placing the sick in the focus of medical interest, the Polish
      school taught future physicians to see in them suffering fellow men who should be
      embraced with care, compassion, and Christian charity. Such an approach to the
      ethical aspect of medical philosophy became incorporated into an education
      towards humane values, responsibility for ones' life and health in the spirit of
      the ethics of care.

PMID- 9933891
TI  - Oaths, laws, and declarations in the studies of medical ethics in Lithuania.
AB  - The article aims at: (a) elucidating the evolution of ethical principles in
      Lithuanian medical practice, associating it with the past and present changes
      taking place in social life, from the so-called "free-of-charge" medical service
      to paid insurance and private medical service; (b) debating the newly-established
      principles of the patients' autonomy, patient's informing, and veracity by
      interpreting the traditional Hippocratic principles of beneficence (usefulness)
      and nonmaleficence (harmlessness), as well as confidentiality, with respect to
      the documents of the World Medical Association; (c) acquainting the readers with
      ethical education at the Kaunas University of Medicine, basing the rules of
      professional conduct on accepted oaths, codes, and declarations; and (d) inviting
      medical students and health care practitioners to take part in the discussion to
      facilitate the solution of ethical dilemmas of medicine, which arise in practical
      work, and pose difficult and controversial problems. I briefly describe the
      situation in Lithuanian society which gave rise to the changes in the field of
      medicine. We relied on universally accepted oaths, codes, and declarations in
      interpreting medical ethical principles. The experience gained in academic
      studies on medical ethics at the Kaunas University of Medicine was also described
      by pointing to ethical dilemmas and their possible solution.

PMID- 9933892
TI  - Teaching history of medicine at Russian medical schools: past, present, and
      future.
AB  - Teaching history of medicine at Russian medical schools has a long tradition. It
      always reflected the general political situation in the country. The present
      program has been approved by the Ministry of Health 10 years ago. History of
      medicine is an obligatory subject taught at the first or second year of medical
      school. The course usually has 40 hours, equally split between lectures and
      seminars, and the program is focused on Russian medicine. Here we analyze the
      existing textbooks on the history of medicine and their drawbacks
      (ideologization, inventing of national priorities in medical discoveries, and
      avoiding the 20th-century medicine). To improve teaching of the history of
      medicine, longer courses and written exams are needed. There is also an evident
      need of writing a new textbook on the history of medicine.

PMID- 9933893
TI  - Learning medical history in Oslo: training for medical practice.
AB  - The teaching in medical history at the University of Oslo, Norway, is given as an
      integrated part of the student training for practical work in health care and
      community health. I summarize here the underlying argumentation and the teaching
      experiences, concluding that this is felt as an effective way to convey relevant
      medical historical knowledge and skills to the future doctors.

PMID- 9933894
TI  - Dr Ivan Pintar and his contribution to the development of history of medicine in
      Slovenia.
AB  - The Medical School of the Ljubljana University has a long lasting tradition in
      teaching the history of medicine. Since 1934, all students of medicine and
      dentistry in Slovenia have attended the courses in history of medicine which were
      and still are mandatory. The first years of lectures on the history of medicine
      at the Ljubljana University Medical School coincided with the struggle for the
      establishment and recognition of a full medical curriculum in Slovenia. Dr Ivan
      Pintar (1888-1963), the first lecturer of the history of medicine (1934-1963),
      was a man of great ethical and national values and an ardent advocate for the
      promotion of Slovene contribution to medical culture in Slovenia, former
      Yugoslavia, and Europe. Pintar's concept of history of medicine included general
      historical, sociological, ethical, cultural, psychological, biotechnical, and
      other aspects. During 30 years of his endeavors, he did a pioneer work in the
      research on the history of medicine in Slovenia. For many years he was the editor
      of the Medical Chamber Bulletin, chairman of the Slovene Medical Society, and the
      founder of the Section for the History of Medicine in 1951. He wrote the first
      Slovene textbook on the history of medicine and published many articles on
      prominent physicians from Slovenia. He paved the way for the new generation of
      medical historians in Slovenia. Owing to him, contemporary Slovene physicians and
      dentists are aware of the importance of professional tradition. They know how to
      use the past experiences for new achievements.

PMID- 9933895
TI  - Study of the history of medicine in Georgia.
AB  - There are different approaches to teaching the history of medicine in different
      countries. Teaching the history of medicine in Georgia is bound to its
      traditional medicine. Georgian medicine originated at the crossroads of the East
      and West and thus integrates the principles of both medical traditions. The
      Research Department of the History of Georgian Medicine and Traditional Medicine
      at Experimental and Clinical Medical Institute of Tbilisi State University has,
      over 40 years, collected a unique material on Georgian folk medicine, including
      thousands of recipes and hundreds of active components of herbal, animal, and
      mineral origin. Our project for the future is to prepare National Formulary of
      Georgian Medicine. In the work with students, we aim to teach them the basis of
      Chinese, Indian, Caucasian, Arabian, American, Australian, and African folk
      medicine, the basis of homeopathy and antroposophy, paleopathology, and
      bioarcheology so that they incorporate them into modern medicine and clinical
      practice.

PMID- 9933896
TI  - Allergy to Parietaria officinalis pollen.
AB  - Parietaria pollen allergens (officinalis, judaica, lusitanica, creatica) are one
      of the most common causes of pollinosis in the Mediterranean (Spain, France,
      Italy, and Croatia). Parietaria has very long period of pollination, often
      reaching peaks of more than 500 grains/m3 of air at the beginning of June, and
      very strong allergenic properties. There is a significantly positive correlation
      for the newcomers between the intensity of the skin test reaction and
      concentration of specific serum IgE with the length of residence in the area,
      whereas autochthonous patients show a negative correlation between the age and
      intensity of hypersensitivity. This suggests that the environment encountered at
      birth may have a decisive role in the development of allergic respiratory
      diseases. Due to structurally similar pollen antigens in different Parietaria
      species, they are all equally useful in diagnosis and treatment of allergy,
      regardless of the pollen species to which the patient is sensitive or the
      prevalent species in the area. In our hands, specific immunotherapy with
      subcutaneous injections of partially purified, characterized, and standardized
      pollen extract of Parietaria allergen proved effective. It was possible to define
      an optimal maintenance dose of antigen per injection. During (years of) therapy,
      we observed an initial increase in total serum IgE concentration and increase in
      allergen-specific serum IgG blocking antibodies, decrease in allergen-specific
      serum IgE concentration and amount of histamine released from peripheral blood
      leukocytes challenged in vitro with the allergen, as well as in symptom and
      additional medication scores.

PMID- 9933897
TI  - Medical effects of internal contamination with uranium.
AB  - The purpose of this work is to present an outline of the metabolic pathways of
      uranium isotopes and compounds, medical consequences of uranium poisoning, and an
      evaluation of the therapeutic alternatives in uranium internal contamination. The
      chemical toxicity of uranium has been recognized for more than two centuries.
      Animal experiments and human studies are conclusive about metabolic adverse
      affects and nephro- toxicity of uranium compounds. Radiation toxicity of uranium
      isotopes has been recognized since the beginning of the nuclear era, with well
      documented evidence of reproductive and developmental toxicity, as well as
      mutagenic and carcinogenic consequences of uranium internal contamination.
      Natural uranium (238U), an alpha emitter with a half-life of 4.5x10(9) years, is
      one of the primordial substances of the universe. It is found in the earth's
      crust, combined with 235U and 234U, alpha, beta, and gamma emitters with
      respective half-lives of 7.1x10(8) and 2.5x10(5) years. A special emphasis of
      this paper concerns depleted uranium. The legacy of radioactive waste,
      environmental and health hazards in the nuclear industry, and, more recently, the
      military use of depleted uranium in the tactical battlefield necessitates further
      insight into the toxicology of depleted uranium. The present controversy over the
      radiological and chemical toxicity of depleted uranium used in the Gulf War
      warrants further experimental and clinical investigations of its effects on the
      biosphere and human organisms.

PMID- 9933898
TI  - Schild's equation and the best estimate of pA2 value and dissociation constant of
      an antagonist.
AB  - Calculation of the pA2 value and dissociation constants for an antagonist from
      the effects observed on isolated smooth muscles can be done in two ways: using
      Schild's plot procedure or Schild's equation. In our study we used the effects of
      muscarinic antagonists observed in experiments on isolated human and feline
      stomach and rat gastric fundus. Only the estimates of pA2 values and dissociation
      constants made using the Schild's equation on the basis of the lowest antagonist
      concentrations were not significantly different from the values calculated using
      the Schild's plot procedure. This suggest that, when it is impractical to perform
      the full Schild's plot procedure, the best estimate of pA2 values and
      dissociation constants can be done with the lowest antagonist concentration that
      significantly inhibits the effects of an agonist on an isolated smooth muscle
      preparation.

PMID- 9933899
TI  - Autopsy findings and clinical diagnoses: retrospective study of 3,117 autopsies.
AB  - AIM: To determine the extent of agreement between clinical and autopsy findings.
      METHODS: A 14-year retrospective study (1982-1995) of autopsies from the
      Departments of Internal Medicine and Surgery was performed at the Zagreb
      University Hospital Center, Croatia. The autopsy findings were compared with the
      clinical diagnoses. RESULTS: The autopsy rate among hospital deaths ranged
      between 23% and 33%. The overall rate of major discrepancies was 11.6% for all
      autopsy reports. The most common cause of death were cardiovascular diseases
      (40.9%), followed by malignancies (25.2%) and infections (12.9%). Among all
      cardiovascular diseases, myocardial infarction was the most frequently diagnosed
      (17.9%) and was misdiagnosed by clinicians in 16.5% of the cases. Incorrectly
      diagnosed malignancies were found in only 5.7% of the cases; hematological and
      lymphoid malignancies (48.8%) were the most common neoplasms and were usually
      confirmed before death. Infections were found in 46.9% of all autopsies.
      Bacterial pneumonias and peritonitis were overlooked in 67.5% and 23. 5% of the
      cases, respectively, in which they existed together with another serious
      condition. CONCLUSIONS: Modern technology has not improved the overall accuracy
      of clinical diagnoses. When an autopsy should be performed is still a matter of
      discussion.

PMID- 9933900
TI  - Corrected formula for the calculation of the electrical heart axis.
AB  - The calculation of the heart axis in the frontal plane can be performed with the
      combination of any two leads. The use of combination of bipolar (I, II, III) and
      unipolar leads (aVR, aVL and aVF) can produce wrong results. Calculation of the
      electrical axis from leads I and aVF without correction (sometimes used in ECG
      recorders): EA= Arctan (aVF/I) results in lower values (in our study: 34 4 , n =
      48) as compared to the values obtained with formula that uses leads I and II: EA=
      Arctan ((2*II-I)/(Sqr(3)*I)) (axis = 33+/-7 degrees, n=48; p<0.005, paired t-test
      with Bonferroni correction) or with corrected formula which uses leads I and aVF:
      EA=+/-Arctan ((2*aVF)/(Sqr(3)*I)) (axis = 374 degrees, n=48; p<0.005, paired t
      test with Bonferroni correction). The correction factor 2/Sqr(3) is required
      because the unipolar and bipolar leads have different strengths. Although the
      difference rarely reach clinical significance, our results suggests that the ECG
      recorders should be proofed on formulas used for the calculation of the
      electrical axis.

PMID- 9933901
TI  - Symptomatology and development of urolithiasis in children with frequency-dysuria
      syndrome associated with hypercalciuria.
AB  - To investigate the long-term outcome of the frequency-dysuria syndrome (FDS) with
      hypercalciuria (HCU), 19 children (15 girls and 4 boys; age range 15 months to 10
      years) who presented with FDS alone (N=9) or with other associated clinical
      features (N=10; 6 with gross hematuria, 3 with microscopic hematuria and 1 with
      abdominal pain) were followed-up over 720 patient-months. Calcium loading test
      indicated absorptive HCU in 12 patients, renal HCU in 2, and in 5 the test was
      inconclusive. All patients were treated with a standard protocol after diagnosis.
      During follow-up, FDS recurred in 4 children, gross hematuria in 3, lumbar pain
      in 5, and 7 children developed urolithiasis within 3 to 60 months. The latter 7
      children (4 with absorptive HCU and 1 with renal HCU) tended to be older than the
      other 12 (7.14 vs 5.08 years; p=0.11) and required a longer time to normalize
      urinary calcium excretion (16 vs 7 months; p <0.01). The initial urinary calcium
      excretion was similar between the patients with and those without stones (5.53 vs
      5.6 mg/kg/d). In all other parameters measured, there were no statistically
      significant differences between the patients who initially presented with FDS
      alone and those with FDS accompanied with other urinary symptoms. We conclude
      that HCU and FDS in children can vary considerably in the clinical mode of
      presentation as well as its sequels. Significant risk for urolithiasis burdens
      the children who require a longer time (>12 months) to normalize their
      hypercalciuria.

PMID- 9933902
TI  - Penetrating injuries of heart and great vessels in patients wounded during the
      1992-1994 war in Bosnia and Herzegovina.
AB  - AIM: To present characteristics of heart and great vessel injuries in patients
      wounded during the 1992-1994 war in Bosnia and Herzegovina and their management
      in conditions of lack of complex diagnostic and therapeutic procedures. METHODS:
      Retrospective analysis was performed on the medical records of 31 patients
      treated for cardiac and great vessel injuries at the Department of Surgery, Tuzla
      University Hospital, between January 1992 and December 1994. RESULTS: The most
      frequent localization of the injuries was the right and left ventricles (each 10
      cases), left atrium in 5, superior caval vein in 5, and inferior caval vein in 5
      cases. Isolated pericardial injury was found in 5 cases. Immediately after
      injury, 22 injured suffered from shock, 7 from pericardial tamponade, and 2 were
      in a stable state. The mortality rate was 58%. Eight patients died during the
      operation as a consequence of bleeding. The highest mortality rate was recorded
      in the injuries of the left ventricle followed by the injuries of the in right
      ventricle and of superior caval vein. All 4 patients with multiple heart and
      great vessel injuries died. Mortality rate was significantly higher in patients
      who suffered from shock than in those who suffered from tamponade. CONCLUSIONS:
      Penetrating war injuries of heart and great vessels are among the most serious
      injuries in war. These injuries require prompt treatment to save life, but this
      is hardly manageable in hospitals without cardiopulmonary bypass facilities.

PMID- 9933903
TI  - Type, severity, location, and timing of battle casualties in a Croatian Army
      brigade during an offensive action in 1992.
AB  - AIM: To analyze the type, severity, location, and timing of casualties in a
      Croatian Army brigade during an offensive action against enemy forces of about
      two infantry battalions timely prepared for defense. METHODS: Casualties were
      analyzed according to bilateral manpower and equipment conditions, morale, time
      of the day, weather conditions, type of ground where the action took place,
      quality of planning and steering the course of the action, and especially the
      medical help. The action was carried out along one main and two auxiliary
      directions, including river crossing. The action involved about 1,000 soldiers
      and took 7 hours. It was divided into three phases: approaching the enemy, direct
      contact, and self-imposed retreat and evacuation. Medical care for the injured
      soldiers was organized in echelons, relying on civilian health care institutions.
      RESULTS: During the action, 92 casualties were recorded. The mean injury severity
      according to the Abbreviated Injury Scale (AIS) was 2.9+/-1.4. The highest
      proportion of casualties occurred on the main direction (48 or 52.2%) but the
      most severe injuries were inflicted on the second auxiliary direction (mean AIS,
      2.6+/-1.4). Extremely severe injuries (mean AIS, 2.0+/-1. 4) were recorded on the
      second auxiliary direction during the phase of retreat after a successfully
      performed action. However, regarding the whole action, the observed differences
      did not prove to be statistically significant. CONCLUSIONS: Offensive action was
      properly planned and successfully led during the first two phases. Evacuation and
      retreat of the brigade were in part poorly organized. Health care for the
      soldiers functioned well throughout the action.

PMID- 9933904
TI  - Assessment of working conditions in a modern Russian milk processing plant from
      the aspect of occupational medicine.
AB  - AIM: Assessment of harmful industrial factors caused by work conditions in a
      modern milk processing plant. METHODS: Work conditions, rest, nutrition, medical
      service, and subjective health indices among the employees in a new milk
      processing plant were studied. We used a specially formed questionnaire;
      instrumental measurements of microclimate parameters, noise, and illumination at
      workplace; laboratory physical and chemical evaluation of air pollution with
      aerosols and gases in the plant premises; chronometric studies determining the
      workers' activity during the working day location, and physical and psychological
      body exertion at the time of industrial activities; and assessment of design and
      operating documents of the plant. Laboratory studies included 157 workers, 1,724
      tests, 26 chronometric studies, and analysis of 11 plant's documents. RESULTS:
      Unfavorable microclimatic conditions, noise, inadequate illumination, air
      pollution with dust and toxic substances, physical workload, increased demand for
      concentration, and monotony of labor in mass production professions were found. A
      great proportion of workers was dissatisfied with their working conditions and
      many suffered from occupational diseases and work-related diseases. CONCLUSIONS:
      The conditions of work in the studied milk processing plant may be classified as
      harmful and dangerous. The flaws in technological process, omissions in design
      and construction of the plant, as well as its improper exploitation aggravated
      industrial harmful factors. In combination with unsatisfactory organization of
      rest, nutrition, and medical services in the plant these factors may affect the
      workers' health and cause general and occupational diseases.

PMID- 9933905
TI  - Laparoscopic management of the cornual pregnancy.
AB  - Traditional treatment of interstitial pregnancy includes cornual resection or
      hysterectomy by laparotomy, but advanced minimally invasive surgery allows
      successful endoscopic management. We report a case where interstitial pregnancy
      was successfully diagnosed by ultrasound and treated by laparoscopy. Patient had
      an unremarkable postoperative course. This case demonstrates that a laparoscopic
      approach toward cornual pregnancy is possible.

PMID- 9933906
TI  - Zimmerman-Laband syndrome: An unusually early presentation in a newborn girl.
AB  - We report on a female newborn, the youngest patient with Zimmermann-Laband
      syndrome hitherto reported. She had gingival hyperplasia, bulbous soft nose and
      ears, hypoplastic toenails, and hyperextensibility of the joints, as well as deep
      palmar and plantar creases, a sign not previously described in literature.

PMID- 9933907
TI  - Fast events in protein folding: the time evolution of primary processes.
AB  - Most experimental studies on the dynamics of protein folding have been confined
      to timescales of 1 ms and longer. Yet it is obvious that many phenomena that are
      obligatory elements of the folding process occur on much faster timescales. For
      example, it is also now clear that the formation of secondary and tertiary
      structures can occur on nanosecond and microsecond times, respectively. Although
      fast events are essential to, and sometimes dominate, the overall folding
      process, with a few exceptions their experimental study has become possible only
      recently with the development of appropriate techniques. This review discusses
      new approaches that are capable of initiating and monitoring the fast events in
      protein folding with temporal resolution down to picoseconds. The first important
      results from those techniques, which have been obtained for the folding of some
      globular proteins and polypeptide models, are also discussed.

PMID- 9933908
TI  - Proton-coupled electron transfer.
AB  - Proton-coupled electron transfer (PCET) is an important mechanism for charge
      transfer in a wide variety of systems including biology- and materials-oriented
      venues. We review several areas where the transfer of an electron and proton is
      tightly coupled and discuss model systems that can provide an experimental basis
      for a test of PCET theory. In a PCET reaction, the electron and proton may
      transfer consecutively (ET/PT) or concertedly (ETPT). The distinction between
      these processes is formulated, and rate-constant expressions for the two reaction
      channels are presented. Methods for the evaluation of these rate constants are
      discussed that are based on dielectric continuum theory. Electron donor hydrogen
      bonded-interface electron acceptor systems displaying PCET reactivity are
      presented, and the rate-constant expressions corresponding to the ETPT and ET/PT
      channels for several model reaction complexes are evaluated.

PMID- 9933909
TI  - Computer simulations with explicit solvent: recent progress in the thermodynamic
      decomposition of free energies and in modeling electrostatic effects.
AB  - This review focuses on recent progress in two areas in which computer simulations
      with explicit solvent are being applied: the thermodynamic decomposition of free
      energies, and modeling electrostatic effects. The computationally intensive
      nature of these simulations has been an obstacle to the systematic study of many
      problems in solvation thermodynamics, such as the decomposition of solvation and
      ligand binding free energies into component enthalpies and entropies. With the
      revolution in computer power continuing, these problems are ripe for study but
      require the judicious choice of algorithms and approximations. We provide a
      critical evaluation of several numerical approaches to the thermodynamic
      decomposition of free energies and summarize applications in the current
      literature. Progress in computer simulations with explicit solvent of charge
      perturbations in biomolecules was slow in the early 1990s because of the
      widespread use of truncated Coulomb potentials in these simulations, among other
      factors. Development of the sophisticated technology described in this review to
      handle the long-range electrostatic interactions has increased the predictive
      power of these simulations to the point where comparisons between explicit and
      continuum solvent models can reveal differences that have their true physical
      origin in the inherent molecularity of the surrounding medium.

PMID- 9933910
TI  - Social identity and individual productivity within groups.
AB  - The purpose of the present research was to show how social identity theory can be
      applied to enhance individual productivity within groups. Three experiments
      manipulated in-group identifiability and importance of the group for one's social
      identity, and compared individual's productivity when working alone to when
      working in a group setting. The group setting in the first study involved either
      a collective of unrelated individuals, a group of participants expecting future
      interaction, or a group working for a group reward. The second study compared
      productivity in groups with four differing interdependent reward structures. The
      final study examine the impact of group members wearing a common uniform (vs. no
      uniform) and the presence (or absence) of an out-group. Results supported the
      general prediction that group productivity would be enhanced by factors that
      increase group categorization and the importance of the group to members' social
      identities (future interaction, interdependent reward structure and
      uniform/outgroup present). However, productivity in groups was not influenced by
      perceptions of the task or identifiability of performance. These findings extent
      social identity theory by suggesting that group members will increase their in
      group position through individual work efforts.

PMID- 9933911
TI  - Politics, moral reasoning and the Defining Issues Test: a reply to Barnett et al.
      (1995).
AB  - Previous research has consistently shown that those on the political Right tend
      to prefer or use conventional or Stage 4 moral reasoning, while those on the
      political Left prefer principled or Stage 5 reasoning (cf. Kohlberg, 1976). One
      interpretation of this finding is that developmental level of moral reasoning
      influences a person's political views, another that the moral 'stages' associated
      with contrasting political positions are in fact contrasting politico-moral
      ideologies and that people choose the form of moral reasoning which best
      expresses their own political identity. We report four studies to test aspects of
      these alternatives. Participants (N = 50) in Study 1 rated moral arguments
      representing different stages as differentially relevant to people of varying
      political persuasions. In Study 2, participants (N = 106), assigned to play the
      role of constituency political parties (either Labour or Conservative) selecting
      candidates to represent their party, evaluated imaginary candidates
      differentially as a function of the kinds of moral arguments the candidates
      expressed. In Study 3 (N = 61), principled and particularly conventional moral
      arguments were again found to express contrasting political identities. In Study
      4 (N = 51) a manipulation of the salience of participants' political identity
      produced as predicted high correlations between moral reasoning scores and
      measures of political attitudes when political identity was salient but not when
      personal identity was salient. The findings overall, however, only partially
      support the view that political identity influences moral reasoning. We conclude
      that, although degree of preference for conventional or Stage 4 reasoning is a
      function of political identity, principled reasoning may be unrelated to
      political orientation. We also propose that these two forms of reasoning do not
      reflect successive development stages and that preference for one may be
      independent of preference for the other.

PMID- 9933912
TI  - Monoclonal antibodies to 2,4-dichlorophenol hydroxylase as probes for the 2,4-D
      degradative phenotype.
AB  - Two different monoclonal antibodies (MAb) were raised against 2,4-dichlorophenol
      hydroxylase (DCP-hydroxylase) of Ralstonia eutropha JMP134 (pJP4), the second
      enzyme in the 2,4-D-degradative pathway of this bacterium. The utility of these
      antibodies in detecting and characterizing 2,4-D-degrading soil bacteria was
      investigated. One MAb (F6) reacted with DCP-hydroxylase from 27 out of 36 strains
      tested, while the other (MAb C3) reacted with only 17 isolates. When used with
      the colony blot technique, MAb F6 was useful for detecting cross-reacting strains
      on plates of pure cultures or of mixtures containing nondegraders even when 2,4-D
      degraders were outnumbered 60 to 1. 2,4-D-degrading strains could also be
      detected from plates spread with enrichment cultures but not from primary
      isolation plates spread from soil dilutions, presumably because the ratio of
      degraders to nondegraders was too low. Colonies of some strains that were very
      distantly related genetically, but produced functionally similar DCP-hydroxlase
      enzymes, were detected by MAb F6. This result suggests that MAbs could be useful
      for detecting functionally similar proteins expressed from tfdB analogs, even in
      the absence of detectable DNA homology between the genes encoding them.

PMID- 9933913
TI  - Localization of a phosphatidylglycerol/phosphatidylinositol transfer protein in
      Aspergillus oryzae.
AB  - The subcellular localization of the phosphatidylglycerol/phosphatidylinositol
      transfer protein (PG/PI-TP) of Aspergillus oryzae was investigated using Western
      blot analysis of the cell protein extracts, a cellular membrane fractionation
      technique, and transmission electron microscopy. The PG/PI-TP, as detected by
      Western blot analysis with a specific immune serum, was found to be mainly
      cytoplasmic and partly associated with intracellular membranes. A fractionation
      experiment was conducted after homogenization of the filamentous fungus mycelium.
      The endoplasmic reticulum, Golgi-like vesicles, and the plasma membrane were
      separated by isopycnic ultracentrifugation on a sucrose gradient, and our data
      revealed that the immunodetected PG/PI-TP was only associated with the Golgi-like
      apparatus. All these results were documented by electron microscopy and indicate
      here for the first time that there exists a specific phospholipid transfer
      protein in a filamentous fungus that is localized in the cytoplasm and associated
      with Golgi-like vesicles.

PMID- 9933914
TI  - A novel method for hybridization of Saccharomyces species without genetic
      markers.
AB  - Protoplasts of Saccharomyces cerevisiae were inactivated by treatment with
      different concentrations of antifungal compounds for various periods. Of the 14
      compounds tested, N-ethylmaleimide proved to be the most efficient. The
      inactivation effect was fully reproducible. The inactivated protoplasts could be
      reactivated and still function as fusion partners. They were fused with untreated
      protoplasts by polyethylene glycol treatment and produced viable hybrid cells.
      Nuclear and extrachromosomal genetic analysis and chromosome separation of the
      fusion products from fusion experiments involving inactivated and non-inactivated
      protoplasts revealed that N-ethylmaleimide did not affect either of the genomes
      and hence it was perfectly suited for the hybridization of any type yeast cells
      without genetic markers.

PMID- 9933915
TI  - Three new insect-associated species of the yeast genus Candida.
AB  - Three new species of Candida are described that were determined to be genetically
      isolated from all other currently accepted ascomycetous yeasts based on their
      sequence divergence in the species-variable D1/D2 domain of large subunit (26S)
      ribosomal DNA. One of the species was isolated from an ambrosia beetle, whereas
      the other two were from the frass of wood-boring beetle larvae. The new species
      and their type strains are the following: Candida ontarioensis NRRL YB-1246 (CBS
      8502), Candida tammaniensis NRRL Y-8257 (CBS 8504), and Candida trypodendroni
      NRRL Y-6488 (CBS 8505).

PMID- 9933916
TI  - Characterization of an endo-1,3-beta-D-glucanase produced during the interaction
      between the mycoparasite Stachybotrys elegans and its host Rhizoctonia solani.
AB  - The mycoparasite Stachybotrys elegans produces, in addition to a previously
      purified 94-kDa 1,3-beta-glucanase, at least three extracellular 1,3-beta
      glucanases (75, 110, and 180 kDa) when grown on purified cell wall of Rhizoctonia
      solani. We purified to homogeneity an endo-1,3-beta-glucanase of 75 kDa which
      possesses a low K(m) value of 20 micrograms laminarin.mL-1 and is most active at
      pH 5.0 and 40 degrees C. Polyclonal antibodies raised against both the 75- and 94
      kDa 1,3-beta-glucanases indicate that they are immunologically related but do not
      cross-react with the 110- and 180-kDa glucanases. Exposure of growing hyphal tips
      of R. solani to the pure 75-kDa 1,3-beta-glucanase caused them to swell and lyse.
      A transient increase of the 75-kDa 1,3-beta-glucanase with a concomitant decrease
      of the 94-kDa 1,3-beta-glucanase and the appearance of a 20-kDa protein were
      observed at the point of interaction between R. solani and Stachybotrys elegans
      on plates. Evidence suggesting a precursor-product relationship between the two
      1,3-beta-glucanases is provided. Our results indicate that the 75-kDa 1,3-beta
      glucanase may be involved in Stachybotrys elegans mycoparasitism.

PMID- 9933917
TI  - Evaluation of the oxolinic acid--esculin--azide medium for the isolation and
      enumeration of faecal streptococci in a routine monitoring programme for bathing
      waters.
AB  - m-Enterococcus agar (m-Ent) has been generally considered the reference medium
      for faecal streptococci in bathing waters. However, it shows several
      shortcomings, and therefore it is important to test newly developed media that
      can guarantee more precise results. In this sense, the recently described
      oxolinic acid--esculin--azide agar medium (OAA) and m-enterococcus agar (m-Ent)
      were comparatively evaluated for the detection of faecal streptococci from
      seawater and fresh water. The OAA medium showed a significantly higher relative
      recovery percentage and specificity for both types of water than m-Ent. A similar
      spectrum of species was recorded from both media, Enterococcus faecium being
      predominant in fresh water and Enterococcus faecalis, in seawater. The superior
      performance of the OAA medium in both types of bathing waters, added to the fact
      that it does not require the use of complementary confirmative tests, makes this
      medium an excellent candidate to be employed for monitoring programmes.

PMID- 9933918
TI  - Kytococcus sedentarius (formerly Micrococcus sedentarius) and Dermacoccus
      nishinomiyaensis (formerly Micrococcus nishinomiyaensis) produce monensins,
      typical Streptomyces cinnamonensis metabolites.
AB  - The environmental isolate Kytococcus sedentarius TR-2 was found to be a new
      producer of the oligoketide antibiotics monensin A and B. Electron microscopic
      studies demonstrated that the TR-2 strain had coccoid cells and DNA analysis
      revealed no close relationship to Streptomyces cinnamonensis, a typical monensin
      producer. Production of monensins was also proven with six culture collection K.
      sedentarius strains and three Dermacoccus nishinomiyaensis strains. The secondary
      metabolism of micrococci demonstrates a high degree of instability. Biosynthesis
      of monensins by micrococci endorses a phylogenetic relationship to Streptomyces
      spp.

PMID- 9933919
TI  - Characterization of the expression and immunogenicity of the ns4b protein of
      human coronavirus 229E.
AB  - Sequencing of complementary DNAs prepared from various coronaviruses has revealed
      open reading frames encoding putative proteins that are yet to be characterized
      and are so far only described as nonstructural (ns). As a first step in the
      elucidation of its function, we characterized the expression and immunogenicity
      of the ns4b gene product from strain 229E of human coronavirus (HCV-229E), a
      respiratory virus with a neurotropic potential. The gene was cloned and expressed
      in bacteria. A fusion protein of ns4b with maltose-binding protein was injected
      into rabbits to generate specific antibodies that were used to demonstrate the
      expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a
      previously reported contiguous five amino acid shared region between ns4b and
      myelin basic protein, a purified recombinant histidine-tagged ns4b protein and
      (or) human myelin basic protein were injected into mice to evaluate whether
      myelin-viral protein cross-reactive antibody responses could be generated. Each
      immunogen induced specific but not cross-reactive antibodies. We conclude that
      ns4b is expressed in infected cells and is immunogenic, although this does not
      involve amino acids shared with a self protein, at least in the experimental
      conditions used.

PMID- 9933920
TI  - Size distributions of chylomicrons from human lymph from dynamic light scattering
      measurements.
AB  - Chylomicrons, the vehicles for the transport of exogeneous triglycerides and
      cholesterol in the lymph and the blood, were characterized by their size from
      dynamic light scattering measurements. To achieve an appropriate resolution,
      correlation data were collected over several hours. Analysis was performed with
      an extended version of the regularization method CONTIN, and special attention
      was given to errors in the experimental baseline and to randomness of the
      residuals. The solutions selected by means of Fisher's F-test by CONTIN agreed
      with those obtained with the stability plot of Schnablegger and Glatter, when in
      the case of data of lower statistical accuracy the solution was taken from the
      lower part of the confidence interval of the F-test. The intensity-weighted size
      distributions indicated two classes of particle, their mean diameters being 100
      140 nm and 330-350 nm. The ability to resolve two peaks of such a size ratio is
      demonstrated. The numbers of particles associated with the two peaks were
      estimated by means of the scattering properties of the particles, which showed
      that the overwhelming majority were small ones. This estimation also suggested
      that the mean size of the first peak of the number distribution is significantly
      smaller than the typical size of chylomicrons. This was consistent with the
      finding that the sample contained not only apolipoprotein B-48 but also a similar
      amount of apolipoprotein B-100, which is associated with lipoproteins of smaller
      size. The larger particles of the second peak are probably dietary triglyceride
      rich chylomicrons.

PMID- 9933921
TI  - Cell adhesion monitoring using a quartz crystal microbalance: comparative
      analysis of different mammalian cell lines.
AB  - The quartz crystal microbalance (QCM) has been widely accepted as a sensitive
      technique to follow adsorption processes in gas as well as in liquid
      environments. However, there are only a few reports about the use of this
      technique to monitor the attachment and spreading of mammalian cells onto a solid
      support in culture. Using a QCM-setup we investigated the time course of cell
      attachment and spreading as a function of seeding density for three widespread
      and frequently used cell lines (MDCK strains I and II and Swiss 3T3-fibroblasts).
      Results were found to be in good agreement with the geometrical properties of the
      individual cell types. The shifts of the resonance frequency associated with
      confluent cell layers on top of the quartz resonators were found to be dependent
      on the cell species [MDCK-I: (320 +/- 20) Hz; MDCK-II: (530 +/- 25) Hz; 3T3: (240
      +/- 15) Hz] reflecting their individual influence on the shear oscillation of the
      resonator. These findings are discussed with respect to the basic models of
      materials in contact with an oscillating quartz resonator. We furthermore showed
      by inhibition-assays using soluble RGD-related peptides, that only specific,
      integrin mediated cell adhesion is detected using this QCM approach, whereas the
      sole presence of the cellular body in close vicinity to the resonator surface is
      barely detectable.

PMID- 9933922
TI  - Hydrodynamic properties of mucins secreted by primary cultures of guinea-pig
      tracheal epithelial cells: determination of diffusion coefficients by analytical
      ultracentrifugation and kinetic analysis of mucus gel hydration and dissolution.
AB  - We have used two different approaches to determine hydrodynamic parameters for
      mucins secreted by guinea-pig tracheal epithelial cells in primary culture. Cells
      were cultured under conditions that promote mucous cell differentiation. Secreted
      mucins were isolated as the excluded fraction from a Sepharose CL-4B gel
      filtration column run under strongly dissociating conditions. Biochemical
      analysis confirmed the identity of the high molecular weight material as mucins.
      Analytical ultracentrifugation was used to study the physical properties of the
      purified mucins. The weight average molecular mass (Mw) for three different
      preparations ranged from 3.3 x 10(6) to 4.7 x 10(6) g/mol (corresponding to an
      average structure of 1-2 subunits), and the sedimentation coefficient from 25.5
      to 35 S. Diffusion coefficients ranging from 4.5 x 10(-8) to 6.4 x 10(-8) cm2/s
      were calculated using the Svedberg equation. A polydispersity index (Mz/Mw) of
      approximately 1.4 was obtained. Diffusivity values were also determined by image
      analysis of mucin granule exocytosis captured by videomicroscopy. The time course
      of hydration and dissolution of mucin was measured and a relationship is
      presented which models both phases, each with first order kinetics, in terms of a
      maximum radius and rate constants for hydration and dissolution. A median
      diffusivity value of 8.05 x 10(-8) cm2/s (inter-quartile range = 1.11 x 10(-7) to
      6.08 x 10(-8) cm2/sec) was determined for the hydration phase. For the
      dissolution phase, a median diffusivity value of 6.98 x 10(-9) cm2/s (inter
      quartile range = 1.47 x 10(-8) to 3.25 x 10(-9) cm2/sec) was determined. These
      values were compared with the macromolecular diffusion coefficients (D20,w)
      obtained by analytical ultracentrifugation. When differences in temperature and
      viscosity were taken into account, the resulting D37,g was within the range of
      diffusivity values for dissolution. Our findings show that the physicochemical
      properties of mucins secreted by cultured guinea-pig tracheal epithelial cells
      are similar to those of mucins of the single or double subunit type purified from
      respiratory mucus or sputum. These data also suggest that measurement of the
      diffusivity of dissolution may be a useful means to estimate the diffusion
      coefficient of mucins in mucus gel at the time of exocytosis from a secretory
      cell.

PMID- 9933923
TI  - Dodecylphosphocholine micelles as a membrane-like environment: new results from
      NMR relaxation and paramagnetic relaxation enhancement analysis.
AB  - To further examine to what extent a dodecyl-phosphocholine (DPC) micelle mimics a
      phosphatidylcholine bilayer environment, we performed 13C, 2H, and 31P NMR
      relaxation measurements. Our data show that the dynamic behavior of DPC
      phosphocholine groups at low temperature (12 degrees C) corresponds to that of a
      phosphatidylcholine interface at high temperature (51 degrees C). In the presence
      of helical peptides, a PMP1 fragment, or an annexin fragment, the DPC local
      dynamics are not affected whereas the DPC aggregation number is increased to
      match an appropriate area/volume ratio for accommodating the bound peptides. We
      also show that quantitative measurements of paramagnetic relaxation enhancements
      induced by small amounts of spin-labeled phospholipids on peptide proton signals
      provide a meaningful insight on the location of both PMP1 and annexin fragments
      in DPC micelles. The paramagnetic contributions to the relaxation were extracted
      from intra-residue cross-peaks of NOESY spectra for both peptides. The location
      of each peptide in the micelles was found consistent with the corresponding
      relaxation data. As illustrated by the study of the PMP1 fragment, paramagnetic
      relaxation data also allow us to supply the missing medium-range NOEs and
      therefore to complete a standard conformational analysis of peptides in micelles.

PMID- 9933924
TI  - Effects of pulmonary surfactant proteins SP-B and SP-C and calcium ions on the
      surface properties of hydrophobic fractions of lung surfactant.
AB  - This study focused on two hydrophobic fractions (HF-A and HF-B) isolated from
      porcine lung surfactant (LS) that had similar phospholipid composition, but HF-A
      consisted of the hydrophobic LS specific proteins (SP-B and SP-C), in contrast to
      HF-B. Monolayers spread in a Langmuir trough were formed at the air/water
      interface of both fractions and the rate of adsorption-desorption and the
      respreading potential of the LS constituents was studied during six consecutive
      compression/decompression cycles of the monolayers. By drawing a comparison
      between the behavior of HF-A and HF-B monolayers on the subphase of 150 mM NaCl,
      either with or without additional Ca2+, we estimated the role of hydrophobic LS
      proteins and Ca2+ ions for LS surface activity. The results demonstrated much
      higher ability of the HF-A sample, compared to HF-B, to maintain lower surface
      tension (gamma) during monolayer compression and its better respreading capacity
      during decompression. For instance, at a surface concentration corresponding to
      80 A2 per phospholipid molecule, the HF-A monolayers showed a much lower gamma
      max value (surface tension at 100% of the trough area), being ca. 31.0 mN/m,
      compared to the HF-B monolayers (gamma max approximately equal to 62.0 mN/m). The
      surface tension after compression to 20% of the initial area (gamma min) reached
      ca. 7.0 and 19.0 mN/m in the HF-A and HF-B monolayers, respectively. Better
      respreading of the HF-A monolayers compared to the HF-B monolayers was due to the
      faster adsorption and spreading of LS phospholipids during decompression,
      facilitated by the hydrophobic proteins. As the phospholipid composition of both
      fractions was similar, we showed that the hydrophobic surfactant proteins were
      responsible also for the prevention of the irreversible loss of material from the
      surface during monolayer compression/decompression. The effects observed
      demonstrated also that the hydrophobic surfactant proteins were the stronger
      determinant, compared with Ca2+ ions, for the surface tension decrease and
      respreading of the monolayers during film compression/decompression. For
      instance, when the HF-A monolayers were spread on a subphase with an additional 5
      mM Ca2+ ion content, no significant changes were detected in the gamma min and
      gamma max values between the first and sixth cycle, compared to the monolayers
      spread on a subphase of 150 mM NaCl only. However, in the absence of positively
      charged SP-B and SP-C (HF-B sample) in highly compressed monolayers, Ca2+ ions
      were able to cause the effects shown by SP-B and SP-C, although to a less extent.
      The role of the electrostatic and hydrophobic interactions is discussed for the
      better respreading of LS components in the presence of LS proteins and Ca2+ ions.

PMID- 9933925
TI  - Transport of acetate in mutants of Saccharomyces cerevisiae defective in
      monocarboxylate permeases.
AB  - The strain Saccharomyces cerevisiae W303-1a, able to grow in a medium containing
      acetic acid as the sole carbon and energy source, was subjected to mutagenesis in
      order to obtain mutants deficient in monocarboxylate permeases. Two mutant clones
      exhibiting growth in ethanol, but unable to grow in a medium with acetic acid as
      the sole carbon and energy source, were isolated (mutants Ace12 and Ace8). In
      both mutants, the activity for the acetate carrier was strongly affected. The
      mutant Ace8 revealed not to be affected in the transport of lactate, while the
      mutant Ace12 did not display activity for that carrier. These results reinforced
      those previously found in the strain IGC 4072, where two distinct transport
      systems for monocarboxylates have been described, depending on the growth carbon
      source. It is tempting to postulate that the Ace8 mutant seems to be affected in
      the gene coding for an acetate permease. In contrast, the absence of activity for
      both monocarboxylate permeases in mutant Ace12 could be attributed to a mutation
      in a gene coding for a regulatory protein not detected before.

PMID- 9933926
TI  - RecA-dependent viral burst in bacterial colonies during the entry into stationary
      phase.
AB  - We have explored the nature of the sudden viral amplification observed during the
      ageing of P22-infected lysogenic colonies of Salmonella typhimurium [Ramirez, E,
      and Villaverde, A. (1997) Gene 202, 147-149]. By a comparative analysis of the
      wild-type P22 and a P22 integration mutant, it has been shown that the conditions
      promoting prophage induction occur in only a small portion of the bacterial
      population and briefly during the transition between the exponential growth and
      the stationary phase. The viral burst is RecA-dependent and cannot be reproduced
      in continuous culture by a mere decrease of the growth rate. This suggests that
      the limited viral propagation in colonies is probably linked to heterogeneous
      physiological conditions within colonial populations, distinct from those of the
      homogeneous liquid cultures.

PMID- 9933927
TI  - 2,4-(hydroxyphenyl)-ethanol, an antioxidative agent produced by Candida spp.,
      impairs neutrophilic yeast killing in vitro.
AB  - Culture supernatants of Candida albicans were examined for factors with
      inhibitory activity against the chemiluminescence of human neutrophils. By high
      resolution gel chromatography, a low-molecular-mass chemiluminescence inhibitor
      was isolated. The compound was identified as 2,4-(hydroxyphenyl)-ethanol. Half
      maximum inhibition (IC50) of the chemiluminescence response of neutrophils
      phagocytizing opsonized zymosan or C. albicans occurred at 38.1 +/- 2.3 microM
      and 19.9 +/- 8.3 microM, respectively. As shown by flow cytometry, the compound
      protected C. albicans against phagocytic killing (IC50 = 73.8 +/- 16.9 microM).
      Substantially higher concentrations of the inhibitor were produced by C. albicans
      and C. tropicalis than by C. parapsilosis and C. glabrata, suggesting a potential
      role in pathogenicity ranking.

PMID- 9933929
TI  - Characterisation of Listeria ivanovii isolates from the UK using pulsed-field gel
      electrophoresis.
AB  - Forty-three Listeria ivanovii isolates were collected in the UK between 1991 and
      1997 from: 35 animal infections; two human infections; five foods; and one
      environmental source. A further two type strains of L. ivanovii (subsp. ivanovii
      and subsp. londoniensis) were obtained from a culture collection. These bacteria
      were characterised by conventional phenotypic methods and by pulsed-field gel
      electrophoresis (PFGE) using ApaI and SmaI. Forty-two of the isolates from the UK
      were identified as L. ivanovii subsp. ivanovii and the remaining culture as L.
      ivanovii subsp. londoniensis. Six and four PFGE profiles were obtained using ApaI
      and SmaI digestion respectively; six composite profiles were obtained combining
      the results for both enzymes. The PFGE profile of the UK L. ivanovii subsp.
      londoniensis (isolated from processed shrimps) was similar to the type strain of
      this subspecies and differed from all of the L. ivanovii subsp. ivanovii tested.
      The majority of isolates (38 out of 45) belonged to one profile showing that the
      UK population of this bacterium is much less genetically diverse than similar
      studies have shown for Listeria monocytogenes.

PMID- 9933928
TI  - Purification and characterization of two extracellular proteinases from
      Arthrobacter nicotianae 9458.
AB  - Two extracellular serine proteinases with molecular masses of about 53-55 and 70
      72 kDa, were purified from Arthrobacter nicotianae 9458 and characterized. The
      enzymes differed with respect to temperature optimum, 55-60 and 37 degrees C,
      respectively, tolerance to low values of pH and temperature, heat stability,
      sensitivity to EDTA and sulfhydryl blocking agents, and hydrophobicity. Both
      proteinases were optimally active in the pH range of 9.0 and 9.5, had
      considerable activity at pH 6.0 on alpha s1- and beta-caseins, and tolerated NaCl
      over 5%. Specificity on casein fractions was generally similar and beta-casein
      was more susceptible to hydrolysis than alpha s1-casein. The proteinases of
      Arthrobacter spp. may play a significant role in ripening of the smear surface
      ripened cheeses.

PMID- 9933930
TI  - Iterative selection from a Salmonella typhimurium cosmid library can lead to the
      isolation of an atypically small plasmid.
AB  - We have constructed a DNA library from a virulent Salmonella typhimurium strain,
      in an avirulent strain. The process of selecting the components of interest from
      the library involved iterative growth in liquid culture. This resulted, after
      four cycles, in the culture becoming homogeneous for a single plasmid, which was
      much smaller than the average size for the library. We have identified the larger
      precursor of this plasmid which has two regions of sufficient homology to allow
      recombination resulting in the formation of the small plasmid. S. typhimurium
      carrying the small plasmid have a smaller genetic burden than other members of
      the library and survive better in spent culture medium, facilitating selection on
      repeated subculture. Such rapid adventitious selection has important implications
      for isolation of clones of interest from genomic libraries.

PMID- 9933931
TI  - Bioaccumulation of heavy metals by fimbrial designer adhesins.
AB  - Naturally occurring adhesins bind to specific molecular targets in a lock-and-key
      fashion due to the composition of the binding domain of the adhesin. By
      introduction of random peptide libraries in a suitable surface exposed carrier
      protein it is possible to create and select designer adhesins with novel binding
      affinities. Type 1 fimbriae are surface organelles of Escherichia coli which
      mediate D-mannose sensitive binding to different host surfaces through the FimH
      adhesin, an integral part of these organelles. We have studied the ability of the
      FimH adhesin to display random peptide sequences. By serial selection and
      enrichment procedures specific sequences were identified which conferred the
      ability on recombinant cells to adhere to various metal oxides (PbO2, CoO, MnO2,
      Cr2O3). The properties inherent in these sequences permitted the distinct
      recognition of metals to varying degrees, indicating that this system allow for
      the isolation of peptide sequences with a variety of binding avidities. These
      studies demonstrate the potential and versatility of the FimH display system for
      presenting random peptide sequences. In addition, the possibility exists for the
      construction of microorganisms for the bioaccumulation of heavy metals from the
      environment.

PMID- 9933933
TI  - The F420H2-dehydrogenase from Methanolobus tindarius: cloning of the ffd operon
      and expression of the genes in Escherichia coli.
AB  - The membrane-bound F420H2-dehydrogenase from the methylotrophic methanogen
      Methanolobus tindarius oxidizes reduced coenzyme F420 and feeds the electrons
      into an energy-conserving electron transport chain. Based on the N-terminal amino
      acid sequence of the 40-kDa subunit of F420H2-dehydrogenase the corresponding
      gene ffdB was detected in chromosomal DNA of M. tindarius. Sequence analysis,
      primer extension, and RT-PCR experiments indicated that ffdB is part of an operon
      harboring three additional open reading frames (ffdA, ffdC, ffdD). The
      corresponding mRNA transcript and transcription start sites were determined. All
      four genes could be heterologously expressed in Escherichia coli.

PMID- 9933932
TI  - Cloning and characterization of a gene cluster from Streptomyces cyanogenus S136
      probably involved in landomycin biosynthesis.
AB  - From a cosmid library of Streptomyces cyanogenus S136, DNA fragments encompassing
      approximately 35 kb of the presumed landomycin biosynthetic gene cluster were
      identified and sequenced, revealing 32 open reading frames most of which could be
      assigned through data base comparison.

PMID- 9933934
TI  - Identification and characterisation of IS1383, a new insertion sequence isolated
      from Pseudomonas putida strain H.
AB  - A new insertion sequence (IS1383) was identified on plasmids from Pseudomonas
      putida strain H and its nucleotide sequence was determined. IS1383 contains
      perfect terminal inverted repeats of 13-bp flanking a 1.4-kb internal sequence. A
      single significant open reading frame was identified that can encode a 342-amino
      acid polypeptide which was predicted to be highly basic and to have homology to
      polypeptides known from several other bacterial insertion sequences. At least six
      copies of IS1383 are present on the plasmids pPGH1 and pPGH2, whereas no copy
      could be detected on the chromosome of P. putida strain H. Target duplications
      did not flank the inverted repeats of any of the six IS1383 copies examined.
      Analysis of the integration sites of IS1383 revealed hints for a target
      specificity. Multiple sequence alignments of the transposases, the inverted
      repeats and the integration sites pointed to the assignment of IS1383 into a
      putative new family of insertion sequences defined as the IS1111 family.

PMID- 9933935
TI  - Cloning and complete nucleotide sequence of Acinetobacter radioresistens CMC-1
      AglyA gene encoding serine hydroxymethyltransferase.
AB  - A gene (AglyA) encoding serine hydroxymethyltransferase of Acinetobacter
      radioresistens CMC-1 was cloned and sequenced. Nucleotide sequence analysis of
      AglyA predicted a single open reading frame (ORF) of 1251 bp encoding a 417-amino
      acid polypeptide. Two putative MetR-like binding sites (5'-TGAAACATGAGCT) and (5'
      TGAGCAAAGTTCA), centered at bp -123 and -95 relative to the +1 translation start
      site were found, which have six out of nine and eight out of nine nucleotides
      that match to the consensus sequence of Escherichia coli (5'-TGAANNT/ANNTTCA),
      respectively. The enzyme also showed a high level of homology to other sources of
      serine hydroxymethyltransferase proteins.

PMID- 9933936
TI  - Freeze tolerance and cryoprotectant mobilization in the gray treefrog (Hyla
      versicolor).
AB  - Interstudy differences have been reported in the cryobiology of Hyla versicolor,
      especially for southern vs. northern populations, although laboratory
      conditioning likely was a contributing factor. This study measured freeze
      tolerance and cryoprotectant levels in H. versicolor from a southern population
      (Illinois). Frogs fully tolerated freezing at -1.5 and -3.5 degrees C for 24-48
      hr but their survival rate declined at -5.5 degrees C (< 50%). Calorimetry
      revealed that 46% of the body water froze after 24 hr at -1.5 degrees C. Levels
      of plasma glucose and glycerol were substantially elevated, 14x and 5x
      respectively, in recently thawed frogs vs. unfrozen frogs. Plasma osmolality
      correspondingly rose from 242 to 304 mOsmol/L. Three unfrozen frogs had levels of
      plasma glycerol ranging between 17.1-36.8 mmol/L, suggesting an anticipatory
      response to freezing, but another three unfrozen frogs had a glycerol level of
      1.1 mmol/L. A direct relationship existed between glycerol content and plasma
      osmolality and an inverse relationship was observed between plasma osmolality and
      ice content. Glycerol clearly was a major component of cryo-protectant production
      in these frogs, which was likely essential to their freeze tolerance. The
      cryobiology of Illinois frogs was only marginally less developed than seen in
      northern populations of this species.

PMID- 9933937
TI  - Cloning and characterization of mouse brush border myosin-I in adult and
      embryonic intestine.
AB  - Brush border myosin-I is a class I myosin with calmodulin light chains that has
      been identified in several vertebrate species. In chicken, it is exclusively
      expressed in intestinal epithelial cells where it forms spirally arrayed bridges
      that tether the microvillar actin bundle to the membrane. To facilitate future
      knockout strategies, we have isolated mouse brush border myosin-I cDNA and
      genomic clones. The deduced primary structure of mouse brush border myosin-I is
      homologous to other known brush border myosins-I. Northern blot, immunoblot, and
      immunolocalization studies indicate that the intestine-specific and subcellular
      localization profile of mouse brush border myosin-I are comparable to that
      determined for other brush border myosins-I. Northern analysis during
      embryogenesis revealed a 3.9-kb transcript first detected in 15-day embryos. This
      is in marked contrast to chicken, where brush border myosin-I expression begins
      early in embryogenesis. In situ localization in 17-day embryos indicated that RNA
      expression is restricted to the intestine. Protein expression is first detected
      in 16-day embryos with decreasing levels observed in a proximal to distal
      fashion. Immunolocalization in embryonic intestine revealed that brush border
      myosin-I is evenly distributed on both apical and basolateral membrane domains.
      There is also pronounced localization to a supranuclear region, presumably the
      Golgi apparatus. This suggests that brush border myosin-I may be targeted to the
      plasma membrane on Golgi-derived vesicles rather than by direct targeting to
      microvillar actin cores.

PMID- 9933938
TI  - Sex-determining mechanism in Buergeria buergeri (Anura, Rhacophoridae). III. Does
      the ZZW triploid frog become female or male?
AB  - Both triploids and gynogenetic diploids (GDs) were produced to clarify the
      relationship between the sex-chromosome constitution and the expression of sex in
      the common bell-ring frog, Buergeria buergeri. The sex differentiation of
      triploids in B. buergeri is quite remarkable. Triploid frogs consisted of three
      sex genotypes, ZZZ, ZWW and ZZW. All ZZZ triploids were males, and all ZWW
      triploids were females. It is very interesting that half of the ZZW triploids
      became female, and the other half became male. The GD frogs consisted of two sex
      genotypes, ZW and ZZ, which did not differ from the controls in sex
      differentiation. Since the ratios of ZZ and ZW eggs were significantly different
      among female parents, it is assumed that most (approximately 80-90%) of the eggs
      made pre-reductional division in some females and post-reductional division in
      others during meiosis. It seems that ZW eggs were produced by the occurrence of
      recombination between the centromere and the sex-determining genes in B.
      buergeri. It was also found that the number of Z chromosomes in each cell of
      these triploids and GDs agreed with that of the nucleoli in each cell.

PMID- 9933939
TI  - Rorschach protocols of children and adolescents with severe burns: a follow-up
      study.
AB  - Twenty children and adolescents with severe burns who participated in a Rorschach
      study in 1992 were reexamined in 1995. The Rorschach variables that were most
      deviant from normative table values were the same (X + %; EgoC; Afr; T; EA; P;
      WSumC; SCZI; DEPI; CDI; and Fr, rF) that had been found in 1 or more other
      studies examining Rorschach variables with individuals of all ages who had been
      traumatized by different events. Although group mean codes were similar across
      Rorschach administrations, a Spearman rank-order correlation coefficient of -.776
      indicated that the group as a whole produced more pathological responses in 1995
      than they did in 1992, with individual protocol pairs revealing changes between
      constrictive to flooded or flooded to constrictive records.

PMID- 9933940
TI  - An investigation of malingering posttraumatic stress disorder on the Personality
      Assessment Inventory.
AB  - Utilizing the Personality Assessment Inventory (PAI; Morey, 1991), this study
      aimed to isolate a pattern of responding that is indicative of an attempt to
      malinger posttraumatic stress disorder (PTSD). The PAI profiles of 116 male
      participants were examined. Profiles of a group of 29 alcohol-abusing veterans
      with a primary Axis I (American Psychiatric Association, 1994) diagnosis of PTSD
      and a group of 30 alcohol-abusing veterans with no other diagnoses were compared
      to those of 27 undergraduate men instructed to feign PTSD. Control data were
      obtained from another group of 30 undergraduates. The student malingerers
      produced PAI profiles that were significantly different from the veterans with
      PTSD. Seven scales distinguished the malingerers from the veterans with an actual
      diagnosis of PTSD. Malingerers tended to overexaggerate pathology, inflating
      their scores on many clinical scales greater than the mean of the PTSD sample.
      Malingerers also scored higher on Morey's (1993) 8-item Malingering Index than
      either group of veterans and the controls. Only 2 scales reliably differentiated
      alcohol-abusing veterans with PTSD from those without the disorder. The
      implications of these findings in the diagnosis of PTSD are discussed.

PMID- 9933941
TI  - Evaluating anxiety and depression in HIV-infected patients.
AB  - Because there is a large overlap between HIV manifestations and somatic symptoms
      of anxiety and depression, it is crucial to use measures that do not contain
      somatic items to validly and reliably assess these psychological states in HIV
      infected patients. The purpose of this study was to assess the psychometric
      properties of the Hospital Anxiety and Depression Scale (HADS), a questionnaire
      that does not include any somatic items, in HIV-seropositive individuals. Because
      the study was conducted among French Canadian individuals, the quality of the
      translation was 1st subjectively and empirically assessed. Then, the psychometric
      properties of the HADS were evaluated in 162 HIV-seropositive patients, who, in
      addition to the HADS, also completed the Beck Depression Inventory (BDI) and the
      State-Trait Anxiety Inventory. The French Canadian version used was found to be
      subjectively and empirically equivalent to the original English version.
      Moreover, results of this study demonstrated a bifactorial structure with factors
      corresponding to the HADS subscales, an excellent internal consistency and test
      retest reliability, a very good convergent validity, and an acceptable
      discriminant validity. Strikingly, in contrast to the BDI, HADS scores were found
      to be unconfounded by the presence of HIV symptomatology. The HADS appears to
      represent the best currently available self-report scale to reliably and validly
      assess anxiety and depression in HIV-infected patients. The HADS is simple and
      brief to administer (14 items) and may therefore be easily implemented in routine
      HIV care.

PMID- 9933942
TI  - Dichotomous thinking as a sign of suicide risk on the TAT.
AB  - Previous research has supported theoretical claims that dichotomous thinking may
      be a risk factor for suicide. However, the concept of dichotomous thinking is
      vague, and thus far, no measures of it have been developed. This study developed
      a coding scheme useful on Thematic Aperception Test (TAT; Murray, 1943) protocols
      and applicable to other verbal productions to refine the concept of dichotomous
      thinking and to assess its utility as a predictor of suicidality. Suicidal
      patients had a significantly elevated rate of a narrowly defined type of
      dichotomous thinking involving diametric or polarized possibilities. However,
      suicidal and nonsuicidal patients did not differ on weaker forms of dichotomous
      thinking involving nonexclusive or nonbinary alternatives. Suicidal patients
      produced shorter TAT stories than nonsuicidal patients, supporting other findings
      in the literature that suicidal patients tend to be cognitively and affectively
      "shut down." Traditionally designated "suicide cards" also yielded shorter
      stories but did not elicit higher rates of dichotomous thinking.

PMID- 9933943
TI  - Susceptibility of the trauma symptom inventory to malingering.
AB  - This study examined the sensitivity and specificity of the Trauma Symptom
      Inventory (TSI; Briere, 1995), a self-report measure of psychological sequelae of
      potentially traumatic events, to malingering. An optimal cutting score for a
      validity scale--Atypical Responding (ATR)--designed to identify exaggeration or
      other unusual response sets was developed in an analogue sample of 155 college
      students and subsequently applied to TSI profiles from several samples of
      patients with various psychiatric disorders. Use of a cross-validated T-score
      cutoff of 61 and below on the ATR scale produced good sensitivity (81%) and
      specificity (92%) rates in the analogue sample. Participants in the analogue
      sample who reported a history of traumatic experiences were no more able to
      successfully malinger trauma symptoms than were participants without such
      histories. Furthermore, false-positive rates in the clinical samples were
      generally low, suggesting that relatively few genuinely symptomatic individuals
      would be misclassified as malingering.

PMID- 9933944
TI  - Defense mechanisms development in children, adolescents, and late adolescents.
AB  - To replicate and extend Cramer's (1987) original cross-sectional study concerning
      the development of defense mechanisms, the Thematic Apperception Test responses
      of 148 students in Grades 2, 5, 8, 11, and college freshmen were collected and
      scored for denial, projection, and identification using Cramer's Defense
      Mechanisms Manual (1991). Our results supported the notion that the relative use
      of denial and projection decreases and identification increases as a function of
      grade level. The findings provide additional support for the psychoanalytic view
      (Freud, 1966) of an ontogenetic developmental line of defense.

PMID- 9933945
TI  - Dissociative symptomatology in children and adolescents as displayed on
      psychological testing.
AB  - The purpose of this study was to investigate psychological testing features of
      children and adolescents with dissociative disorder diagnoses to provide
      diagnostic information that might facilitate early intervention. The
      psychological testing protocols of 30 children diagnosed with dissociative
      disorders were compared with the testing protocols of 30 consecutive admissions
      to the Sheppard Pratt Hospital who did not receive a dissociative identity
      disorder (DID; formerly termed multiple personality disorder) or dissociative
      disorder not otherwise specified (DDNOS) diagnosis. A rater, blind to the
      diagnosis, scored these protocols for the presence or absence of behavioral and
      testing response variables hypothesized to discriminate between the dissociative
      patients and the mixed group of other diagnoses. Behavioral features
      significantly more common in the dissociative group included forgetting, staring,
      unusual motor behaviors, dramatic fluctuations, fearful and angry reactions to
      stimuli, physical complaints during testing, and expressions of internal
      conflict. Significant indications of dissociation in the test responses included
      images of multiplicity, malevolent religiosity, dissociative coping,
      depersonalized imagery, emotional confusion, extreme dichotomization, images of
      mutilation and torture, and magical transformation. A combination of these
      behavioral and response variables was able to select 93% of the dissociative
      sample. These results add support to the discriminant validity of DID and DDNOS
      as diagnostic categories in childhood and provide clinical information that may
      be useful for early diagnosis of traumatized children with dissociative
      pathology.

PMID- 9933946
TI  - Expression of barley ADP-glucose pyrophosphorylase in Escherichia coli:
      processing and regulatory considerations.
AB  - Full length cDNAs for barley ADP-glucose pyrophosphorylase (AGPase) coding for
      the large subunits of the endosperm and leaf homologues of the enzyme (AGPase-S1
      and -S2, respectively) and for the small subunit protein from endosperm (AGPase
      B1), have been expressed in Escherichia coli. The cDNAs for AGPase-S1 and -S2
      required different induction conditions for their maximal expression and they
      encoded immunologically distinct proteins. The AGPase-S1 that was produced by E.
      coli had the same M(r) (58 kDa) as the corresponding protein in barley crude
      endosperm extracts, whereas the bacteria-produced AGPase-S2 (55 kDa) was larger
      than its counterpart from barley leaf preparations (53 kDa). An enzymatically
      active AGPase expressed in E. coli from a double construct containing cDNAs for
      AGPase-S1 and -B1 subunits was insensitive to the activation by 3
      phosphoglycerate and to inhibition by inorganic phosphate, similarly to the
      enzyme in barley endosperm. Neither AGPase-S1 nor -B1 were active when expressed
      alone in the bacteria. The data are discussed with respect to possible mechanisms
      of intracellular targeting of immature AGPase-S proteins in barley tissues and
      regarding previous data on effector regulation of the barley enzyme.

PMID- 9933947
TI  - Purification of leghemoglobin from nodules of Crotalaria infected with Rhizobium.
AB  - The leghemoglobin from nodules of Crotalaria juncea infected with Rhizobium spp.
      was purified to homogeneity. The protein was purified after precipitation with 40
      80% (NH4)2SO4, and chromatography by anionic exchange and gel filtration. The
      leghemoglobin has a single component and showed an apparent M(r) of ca. 17,300
      and 23,700 determined by SDS-PAGE and gel filtration, respectively. The amino
      acid composition showed that asparagine/aspartic acid, glutamine/glutamic acid,
      alanine, lysine, serine and leucine were the main amino acids. Iron was detected
      only in the band corresponding to the purified protein. The N-terminal amino acid
      sequence for the first 19 residues showed high similarities with several other
      leghemoglobins from other plants.

PMID- 9933948
TI  - Flavonol glycosides from Eschscholtzia californica.
AB  - The aqueous EtOH extract of aerial parts of Eschscholtzia californica Cham.
      yielded six flavonol 3-O-glycosides including two new compounds: quercetin 3-O
      [alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)-beta- glucopyranoside]
      and isorhamnetin 3-O-[alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)
      beta- glucopyranoside]. Their structures were established on the basis of
      spectroscopic studies.

PMID- 9933950
TI  - Involvement of calcium in ACC-oxidase activity from Cicer arietinum seed
      embryonic axes.
AB  - Both in vivo and in vitro ACC-oxidase activities as well as ethylene production
      from embryonic axes of chickpea seeds were strongly inhibited by EGTA, a
      selective extracellular Ca2+ ion chelator, indicating that the influx of Ca2+ is
      important for enzymatic activity. EGTA inhibition was restored by exogenous Ca2+.
      Treatments of embryonic axes with either Verapamil and LaCl3 (both Ca2+ channel
      blockers) or TMB-8 (an intracellular Ca2+ antagonist) provoked an inhibition of
      both ACC-oxidase activity and ethylene production. These results suggest an
      involvement of calcium fluxes and intracellular calcium levels in the activity of
      the last step of the ethylene biosynthetic pathway, which is, in turn, intimately
      correlated with germination of Cicer arietinum seeds.

PMID- 9933953
TI  - Chemical, physical and antimicrobial properties of essential oils of Leptospermum
      scoparium and Kunzea ericoides.
AB  - The major components of commercial New Zealand essential oils of Leptospermum
      scoparium (manuka) and Kunzea ericoides (kanuka) are identified. In the manuka
      oil, monoterpenes are present at low levels (< or = 3%). Sesquiterpene
      hydrocarbons are predominant (> or = 60%) and include groups possessing
      cubebene/copaene, elemene, gurjunene/aromadendrene, farnesene/ caryophyllene,
      selinene, calamenene and cadinene skeletons. Oxygenated sesquiterpenes and
      triketones are present (< or = 30%). The antimicrobial activity of the manuka oil
      was associated with a fraction containing three major and three trace triketones,
      two of the latter were previously unreported. Kanuka oil was characterized by
      high levels of alpha-pinene (> 50%) and lower levels (< 10%) of viridiflorol and
      viridiflorene. GC-MS and GC-FID detector responses to the same components were
      noticeably different for some major components, including the triketones. Non
      commercial manuka oils from different sites differed widely in composition and
      could be separated into four groups by the presence and levels of distinctive
      components. The density and refractive index of manuka and kanuka oils were
      closely correlated with the total sesquiterpene levels. The density of the
      commercial manuka oil was closely correlated with the level of the triketones.
      Simple density measurements enabled discrimination between the commercial oil and
      oils from other sites, and prediction of antimicrobial activity.

PMID- 9933955
TI  - Bio-active cardenolides from the leaves of Nerium oleander.
AB  - A bioactivity directed isolation of the methanolic extract of the fresh,
      uncrushed leaves of Nerium oleander showing a central nervous system (CNS)
      depressant effect in mice has been undertaken. As a result, four CNS depressant
      cardenolides including a new cardenolide, neridiginoside and three known
      constituents, nerizoside, neritaloside and odoroside-H, have been isolated which
      exhibited CNS depressant activity in mice at a dose of 25 mg/kg. The structure of
      neridiginoside was elucidated as 3 beta-O-(D-diginosyl)-5 beta, 14 beta-dihydroxy
      card-20(22)-enolide, using spectroscopic methods including one-dimensional and
      two-dimensional NMR (COSY-45, NOESY, J-resolved, HMQC and HMBC). The known
      compounds have been indentified through spectral studies and comparison of data
      with those reported in the literature.

PMID- 9933954
TI  - 11-oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort,
      Lepidolaena taylorii.
AB  - Four new cytotoxic 8,9-secokauranes have been identified from the liverwort
      Lepidolaena taylorii. The 11-oxygenation found in three of these has not been
      encountered in the 8,9-secokauranes known from higher plants. NMR studies were
      combined with molecular modelling to determine the preferred conformations. Six
      structurally related kauren-15-ones were also found, including three new
      compounds. Some of these compounds showed differential cytotoxic activity against
      human tumor cell lines. The probable mode of cytotoxic action was supported by
      Michael addition of a thiol. Two 8,9-secokauranes were the main cytotoxins in
      another New Zealand liverwort. L. palpebrifolia.

PMID- 9933956
TI  - Steroidal saponins from Asparagus dumosus.
AB  - A new steroidal saponin, dumoside, characterized as (20S)-3 beta, 16 beta
      dihydroxy pregn-5-ene-22-carboxylic acid (22, 16)-lactone-3-O-beta-chacotrioside,
      was isolated from the whole plant of Asparagus dumosus Baker and the structure
      was deduced from spectral data. In addition to dumoside three more steroidal
      saponins characterized as 3 beta-dihydroxy pregn-5,16-dien-20-one 3-O-beta
      chacotrioside, 3 beta, 22 alpha, 26-trihydroxyfurost-5-ene-3-O-beta-chacotrioside
      26-O- beta-D-glucopyranoside and its corresponding 22 alpha-O methoxy analogue
      were also isolated for the first time from this source. The structures have been
      identified with the help of FAB-MS, 1H NMR, 13C NMR and extensive 2D NMR
      spectroscopy, as well as comparison with reported spectroscopic data.

PMID- 9933957
TI  - Comparison of Tetrahymena and Pimephales toxicity based on mechanism of action.
AB  - The toxicity data of 256 chemicals tested in both the 96-h Pimephales promelas
      mortality assay and the 2-d Tetrahymena pyriformis growth inhibition assay were
      evaluated using quantitative structure-activity relationships (QSARs). Each
      chemical was a priori assigned a mode of action of either narcoses or soft
      electrophilicity. Narcoses were separated into nonpolar narcosis, polar narcosis,
      monoester narcosis, diester narcosis, amine narcosis, and weak acid respiratory
      uncoupling based on the presence or absence of specific toxicophores. Toxicity of
      each narcotic mechanism was initially regressed against the 1-octanol-water
      partition coefficient (log K(ow)). The slopes of these log K(ow) based QSARs were
      observed to ascertain whether a relationship exists between the value of the
      slope and the reactivity of the mechanism of action. With both the fish and
      ciliate data nonpolar narcosis was the least reactive mechanism. It was followed
      by the other reversible narcoses. The soft electrophile mode was separated into
      the specific molecular mechanisms of: SN2 reactors, Schiff-base formers, Michael
      type addition, or proelectrophilicity (precursors to Michael-type addition
      chemicals). These mechanisms were represented structurally by the nitrobenzenes,
      aldehydes, polarized alpha-beta unsaturates (e.g., acrylates and methacrylates),
      and acetylenic alcohols, respectively. Electrophilic toxicity was not correlated
      with hydrophobicity. QSARs based on molecular orbital (MO) quantum chemical
      descriptors were used to improve the predictability of the electrophilic
      mechanisms. Relevant descriptors include average superdelocalizability (Svna) for
      the nucleophilic addition of the nitrobenzene; atom x and y acceptor
      superdelocalizability (Ax); and bond order (Bx y) for the Michael-type addition
      of the acrylates; and log K(ow) and atom x net charge (Qx) for the Schiff-base
      forming aldehydes. The pertinent descriptors for proelectrophiles were log K(ow)
      and Svna. Principal differences between the QSARs for the two biological
      endpoints were observed for the ester narcoses, proelectrophiles, and Schiff-base
      forming aldehydes.

PMID- 9933958
TI  - SAR models for estimating the percutaneous absorption of polynuclear aromatic
      hydrocarbons.
AB  - A structure-activity relationship (SAR) of the in vitro percutaneous absorption
      of polycyclic aromatic hydrocarbons (PAH) is described. The data set consisted of
      60 three to seven ring PAH. Over 50 numeric descriptors were generated from the
      modeled molecular structures. Computer aided methods were used to evaluate
      descriptors and develop linear expressions relating the percent of dermally
      applied PAH dose absorbed through skin (PADA) to PAH structure. Three regression
      models with one and two variables were developed. The log octanol/water partition
      coefficient (log P) was the most important variable in determining percutaneous
      absorption. An inverse relationship between log P and the skin penetration
      properties of the PAH was observed. Nearly 40 of 60 PAH tested had PADA-values
      within a factor of two of benzo[a]pyrene (BaP); well over 50 of 60 had PADA
      values within a factor of three. The results lend support to the use of
      isotopically labeled BaP as a surrogate for measuring the dermal flux (in vivo
      and in vitro) and estimating the dermal bioavailability of PAH from complex
      mineral oil and coal-tar derived mixtures.

PMID- 9933959
TI  - Comparison of CoMFA models for Salmonella typhimurium TA98, TA100, TA98 + S9 and
      TA100 + S9 mutagenicity of nitroaromatics.
AB  - Comparative Molecular Field Analysis (CoMFA) was applied to a comprehensive data
      set of heterogeneous nitroaromatics tested in Salmonella typhimurium TA98 and
      TA100 with and without S9 microsomal activation. The four CoMFA models developed
      agree with postulated mechanisms of mutagenicity, and explain over 70% of the
      corresponding mutagenic variance The standard deviation coefficient contours
      common in the four models included high electronic density regions equivalent to
      C4-C5 in the pyrene ring, and an electron deficient site equivalent to C6. These
      areas are associated with high mutagenicity. Electron deficient areas may be
      related with the nitroreductive bioactivation of nitroaromatics. Electron rich
      sites may be involved with oxidative mechanisms analogous to the bioactivation
      pathway of polycyclic aromatic hydrocarbons. The contribution of steric factors
      to mutagenicity follows the order TA98 + S9 > TA98 > TA100 + S9 > TA100. The
      models indicated that increasing bulk perpendicular to the aromatic plane would
      decrease mutagenicity, but increasing the aromatic ring system along a region
      corresponding to C6-C7 in 1-nitropyrene would increase mutagenicity.

PMID- 9933960
TI  - Structure-toxicity relationships for aminoalkanols: a comparison with alkanols
      and alkanamines.
AB  - The relative toxicity (log IGC50(-1)) of 49 selected aliphatic amines and
      aminoalkanols was evaluated in the static Tetrahymena pyriformis population
      growth impairment assay. Excess toxicity, indicated by potency greater than
      predicted for non-polar narcotic alkanols, was associated with both classes of
      test chemicals. Moreover, the aminoalkanols were found to be more toxic than the
      corresponding alkanamines. A high quality 1-octanol/water partition coefficient
      (log K(ow)) dependent quantitative structure-activity relationship (QSAR),
      logIGC50(-1) = 0.78 (log K(ow)) - 1.42; r2 = 0.934, was developed for
      alkanamines. This QSAR represented the amine narcosis mechanism of toxic action.
      No quality QSAR was developed for the aminoalkanols. However, several structure
      toxicity features were observed for this class of chemicals. Two-amino-1-hydroxy
      derivatives being more toxic than the corresponding derivatives, where the amino
      and hydroxy moieties were separated by methylene groups. Hydrocarbon branching
      next to the amino moiety resulted in decreased toxicity. Aminoalkanol alters
      lipid metabolism in T. pyriformis.

PMID- 9933961
TI  - Five new bioactive sesquiterpenes from the fungus Radulomyces confluens (Fr.)
      Christ.
AB  - The three protoilludanes radulone A (1), radulone B (2) and radudiol (3), the
      illudalane radulactone (4) and the illudane radulol (5) were isolated from the
      extracts of the culture fluids of the basidiomycete Radulomyces confluens. The
      structures of the five new compounds were determined by spectroscopic techniques.
      Radulone A (1) is a potent inhibitor of human and bovine platelet aggregation
      stimulated by different agonists, inhibiting preferentially the aggregation of
      human platelets induced by ADP with an IC50 value of 2 microM. In addition 1
      exhibits cytotoxic and antimicrobial activities. The other four compounds
      exhibited weak antimicrobial and cytotoxic activity.

PMID- 9933962
TI  - Phosphorylase phosphatase activity in Saccharomyces cerevisiae 257.
AB  - A phosphatase, active towards phosphorylase a and phosphorylated proteins casein
      and histone II-A, was isolated from Saccharomyces cerevisiae 257. The enzyme
      dephosphorylated glycogen phosphorylase from commercial yeast rendering it
      inactive. The protein phosphatase activity was not influenced by any metal ions.
      Phosphorylase phosphatase activity was slightly stimulated by p-nitrophenyl
      phosphate and inhibited by heparin.

PMID- 9933963
TI  - Peroxidase-polyphenol oxidase association in Dioscorea esculenta.
AB  - A crude enzyme extract from Dioscorea esculenta var. fasiculata tissue subjected
      to ion exchange chromatography on DEAE-Sephadex A-50 column. This procedure
      resolved the extract into two main protein peaks one of which eluted through the
      column relatively unbound while the other protein peak which remained bound to
      the column was eluted with 1.0 M NaCl. Both protein peaks contained polyphenol
      oxidase (PPO) and peroxidase (POD) activities. The non-binding protein peak was
      resolved by gel filtration on Sephadex G-200 into distinct PPO and POD activities
      and by virtue of their apparent molecular weights of 95.5 Kd and 38.0 Kd for PPO
      and POD respectively were determined to be the typical enzymes. The PPO activity
      was completely inhibited invitro by 5 mM polyvinyl pyrrolidone (PVP). The binding
      protein peak was not resolved by gel filtration. It contained PPO activity which
      was not inhibited by PVP and a POD activity which was completely inhibited by
      dithiothreitol (DTT) This ionic protein peak contained 60% of total POD in the
      tissue, has an apparent molecular weight of 56 Kd and is suggested to be a
      strongly anionic peroxidase which also exhibits polyphenol oxidase activity.

PMID- 9933964
TI  - Immobilization of polymethylgalacturonase producing Aspergillus niger on Luffa
      sponge material.
AB  - The vegetable sponge of Luffa cylindrica was studied as a matrix for the
      immobilization of Aspergillus niger 26, producer of polymethylgalacturonase
      (PMG). Entrapped spores could grow and multiply within the lattice of the sponge.
      The influence of loofa sponge inoculum content, initial spore inoculum content,
      and duration of the growth cycle on the enzyme activity and mycelium growth was
      studied. The best yield of PMG was reached with 1 piece of loofa sponge (approx.
      0.10 g dry weight), 10(9) spores per g carrier and 48 h duration of one cycle.
      Data obtained during long-term semicontinuous cultivation showed that production
      capacity increased significantly and the production period was extended more than
      10 times compared with the free cell culture.

PMID- 9933965
TI  - Influence of chemical treatments on glutathione S-transferases of maize with
      activity towards metolachlor and cinnamic acid.
AB  - The subcellular distribution of glutathione S-transferase (GST) activity
      extracted from shoots of 3-day-old etiolated seedlings of maize (Zea mays L.,
      Northrup-King 9283 hybrid) and the induction of soluble and membrane-bound GST
      activity by the safener benoxacor, the herbicide metolachlor and their
      combination (CGA-180937) were investigated. GST activity extracted from maize
      shoots was detected in both cytosolic and microsomal fractions and utilized 1
      chloro-2,4-dinitrobenzene (CDNB), metolachlor, and trans-cinnamic acid (CA) as
      substrates. Soluble GST activity extracted from maize shoots was greater than
      microsomal with CDNB or metolachlor as substrate. Membrane-bound GST activity was
      greater than soluble with cinnamic acid as substrate. Washing the microsomal
      preparations from maize shoots with Triton X-100 increased GST(CA) activity.
      Pretreatment with the safener benoxacor or a formulated combination of the
      herbicide metolachlor with benoxacor induced soluble GST(CDNB), GST(metolachlor)
      and GST(CA) activities in maize shoots. Benoxacor and CGA-180937 induced also
      membrane-bound GST(CDNB) and GST(CA) activities in maize shoots, but did not
      affect membrane-bound GST(metolachlor) activity. These results confirm that maize
      contains multiple GST isozymes that differ in their substrate specificity and
      inducibility by safeners or other chemicals.

PMID- 9933966
TI  - Transgenic potato plants expressing soybean beta-1,3-endoglucanase gene exhibit
      an increased resistance to Phytophthora infestans.
AB  - Soybean beta-1,3-endoglucanase represents a model system for studies on early
      plant responses to infection by fungal pathogens, and it has been implicated in
      the release of elicitors from fungal cell walls. In the present study, potato
      plants were transformed with the soybean beta-1,3-endoglucanase cDNA via
      Agrobacterium delivery system. The transfer of the gene into potato genome was
      confirmed by (i) PCR amplification, (ii) Northern blot analyses, and (iii) an
      increase in the activity of beta-1,3-endoglucanase in transgenic plants. The
      transformation resulted in an increased resistance of selected transgenic plants
      to infection by Phytophthora infestans, an important pathogen.

PMID- 9933967
TI  - Circadian synthesis of light-harvesting-chlorophyll-proteins in Euglena gracilis
      is under translational control.
AB  - Two proteins with apparent molecular masses of 17 and 24 kD that are synthesized
      in a circadian manner in the phytoflagellate Euglena gracilis, were recognized as
      proteins belonging to the family of light-harvesting-chlorophyll-proteins (LHCPs)
      of class I (17 kD) and of class II (24 kD). Identification was achieved by N
      terminal sequencing of the proteins isolated from two-dimensional polyacrylamide
      gels and by detection with an anti-LHCP II serum. While it was found that the
      total amount of LHCPs remains almost constant, when Euglena is grown under
      diurnal conditions (12 h light and 12 h dark), we could show that the amount of
      newly synthesized 17 and 24 kD proteins varies about 20-fold with a maximum of
      synthesis in the light phase. In contrast, the analysis of the mRNA levels at
      different times revealed only minor differences in the stationary concentration
      of the LHCP specific mRNA, indicating that the control of LHCP synthesis is at
      the translational level. Principally, the same finding was obtained using
      inhibitors of transcription. Thus, it is concluded that the expression of LHCPs
      in Euglena gracilis in contrast to that of higher plants is primarily regulated
      at the translational level.

PMID- 9933968
TI  - Correlation between virulence of various strains of mycobacteria and their
      susceptibility to ethanolic extract of propolis (EEP).
AB  - Ethanol extract of propolis (EEP) has antibacterial, antiviral, antiprotozoal and
      antifungal properties, in addition to many biological effects. Our laboratory has
      demonstrated a synergistic effect of EEP and antibiotics on the growth of
      Staphylococcus aureus, and suggested that the bactericidal effect of EEP was
      expressed mainly on virulent mycobacteria rather than on non-virulent
      (attenuated) ones. The present study was designed to reconfirm the latter
      finding, by subjecting 17 different mycobacteria strains to EEP, and evaluating
      whether there is a correlation between the virulence of the mycobacteria strains
      studied and their susceptibility to EEP. Our findings demonstrate that while the
      four non-virulent strains studied are not susceptible to EEP, out of the 13
      virulent strains studied seven are susceptible and six are resistant to it. These
      results suggest that while there is no full correlation between virulence of the
      mycobacteria tested and their susceptibility to EEP, the few strains that were
      resistant to EEP were non-virulent.

PMID- 9933969
TI  - Preliminary report on the effects of propolis on wound healing in the dental
      pulp.
AB  - The purpose of this investigation was to determine the antimicrobial and healing
      potential of propolis on direct dental pulp exposures. This study used 25 adult
      male rats. Pulp exposures were performed and animals were allocated to propolis
      and calcium hydroxide (Ca(OH)2 groups. Animals were killed on days 5, 7, 10, and
      14. The teeth were routinely processed for histological evaluation. Non
      parametric tests were employed to analyze the data. No significant differences
      were found between study groups on the wound healing of the dental pulp. Both
      substances were comparable in exhibiting normal reorganization of the pulp and no
      increased vascularity, and were equally efficacious in maintaining a low
      inflammatory and microbial cell population as well as in stimulating the
      formation of reparative dentin.

PMID- 9933970
TI  - Trypanosoma cruzi epimastigotes express the ouabain- and vanadate-sensitive
      (Na(+)+K+)ATPase activity.
AB  - The presence of (Na(+)+K+)ATPase activity in CL14 clone and NIH NTY strain of
      Trypanosoma cruzi epimastigotes is demonstrated. A Na+ plus K+ stimulated ATPase
      activity is found in both strains. The optimal Na+/K+ ratio is 5:1 and 9:1 in
      CL14 clone and NIH NTY strain, respectively. In both strains, vanadate completely
      inhibits the ouabain-sensitive ATPase activity indicating that it belongs to the
      P-type (E1/E2) family of ion-transporting ATPases. The I50 for vanadate is 0.66
      +/- 0.04 and 0.04 +/- 0.02 microM in CL14 clone and NIH NTY strain, respectively.
      These data indicate that both strains of T. cruzi epimastigotes express the
      ouabain- and vanadate-sensitive (Na(+)+K+)ATPase activity. On the other hand, the
      discrepancy between the parameters analyzed for the inhibitors suggests that they
      express different isoforms of this enzyme.

PMID- 9933971
TI  - L-phenylalanine effect on rat diaphragm acetylcholinesterase and Na+,K(+)-ATPase.
AB  - The effect of different L-phenylalanine (Phe) concentrations (0.24-12.1 mM), on
      acetylcholinesterase (AChE) and Na+,K(+)-ATPase activities of diaphragm
      homogenates from 21-day old rats and pure enzymes, was investigated at 37 degrees
      C. AChE and Na+,K(+)-ATPase activities were determined after preincubation with
      Phe. AChE activity in diaphragm homogenate or in pure eel E. electricus enzyme
      showed a decrease, which reached a maximum of 18% with Phe concentrations of 0.9
      12.1 mM. However lower Phe concentrations (0.24 mM) increased the enzyme activity
      (by approximately 22%), only in the diaphragm homogenate. Diaphragm-associated
      Na+,K(+)-ATPase activity showed a progressive and concentration-dependent
      decrease, by about 30-35% in the presence of high Phe concentrations. Pure enzyme
      activity (from porcine cerebral cortex) was not affected by high Phe
      concentrations (> 0.48 mM), while it was increased by low concentrations. The
      above results suggest: a) A direct inactivating effect of high Phe concentrations
      on AChE and an indirect activating effect induced by low concentrations. b) A
      direct activating effect of low Phe concentrations and an indirect inactivating
      effect of high ones on Na+,K(+)-ATPase. c) The combination of high Phe
      concentrations effects on AChE and Na+,K(+)-ATPase could influence the levels of
      the diaphragm synaptic ACh.

PMID- 9933973
TI  - Nuclear magnetic resonance and mass spectrometric studies on the action of
      proteases on pig articular cartilage.
AB  - Rheumatic diseases are accompanied by a progradient diminution of the cartilage
      layer. Unfortunately, degradation mechanisms (role of different enzymes and
      reactive oxygen species) are not yet understood. Since nuclear magnetic resonance
      (NMR) spectroscopy was often used for the investigation of synovial fluids, the
      aim of the present work was to detect cartilage degradation products upon
      proteolytic digest of cartilage. Cartilage samples were incubated at 37 degrees C
      with phosphate buffer in the absence or presence of different proteases
      (collagenase, trypsin and papain). Supernatants were subsequently assayed towards
      their content of carbohydrate and protein degradation products by NMR (1H- and
      13C-) and MALDI-TOF mass spectrometry. Intense resonances of relatively mobile N
      acetyl side chains (ca. 2.01 ppm) of polysaccharides of cartilage were only
      detectable on digestion with papain. The appearance of these resonances indicates
      intense degradation of the core protein of proteoglycan aggregate of cartilage,
      whereby polysaccharides are released. Additionally, broad resonances at 0.85 ppm
      arising from collagen degradation products were observed upon the action of all
      applied proteases. However, glycine as a marker of exhaustive collagen
      degradation was only observed, if cartilage was digested by collagenase. Using
      more vigorous incubation conditions, additionally high-abundant amino acids of
      collagen (proline, hydroxyproline) could be detected in the 13C-NMR- and the
      MALDI spectra. The observed differences are correlated with the different
      selectivities of the applied enzymes. It is concluded that NMR allows the
      detection of characteristic protein and polysaccharide degradation products. The
      observed differences may be of some relevance for the diagnosis of rheumatic
      diseases.

PMID- 9933972
TI  - Increased levels of lipid oxidation products in rheumatically destructed bones of
      patients suffering from rheumatoid arthritis.
AB  - The new indicator for lipid peroxidation (LPO) processes--9-hydroxy-10,12
      octadecadienoic acid (9-HODE)--was used to investigate, whether LPO processes are
      increased in destructed bone material of patients suffering from rheumatoid
      arthritis (RA) in comparison to surrounded non destructed bone material. The HODE
      content in destructed bones exceeded that of non destructed ones of the same
      patient for a factor of about 3. In addition similar increases in leukotoxines
      and epoxy oleic acid in the destructed bone material were observed, indicating an
      increase of LPO processes in affected bone parts of patients.

PMID- 9933974
TI  - Principles of enzyme thermistor systems: applications to biomedical and other
      measurements.
AB  - This chapter presents an overview of thermistor-based calorimetric measurements.
      Bioanalytical applications are emphasized from both the chemical and biomedical
      points of view. The introductory section elucidates the principles involved in
      the thermometric measurements. The following section describes in detail the
      evolution of the various versions of enzyme-thermistor devices. Special emphasis
      is laid on the description of modern "mini" and "miniaturized" versions of enzyme
      thermistors. Hybrid devices are also introduced in this section. In the sections
      on applications, the clinical/biomedical areas are dealt with separately,
      followed by other applications. Mention is also made of miscellaneous
      applications. A special section is devoted to future developments, wherein novel
      concepts of telemedicine and home diagnostics are highlighted. The role of
      communication and information technology in telemedicine is also mentioned. In
      the concluding sections, an attempt is made to incorporate the most recent
      references on specific topics based on enzyme-thermistor systems.

PMID- 9933975
TI  - Thermal biosensors in biotechnology.
AB  - The application of enzyme thermistor devices for the continuous monitoring of
      enzymatic processes is described. Different hardware concepts are presented and
      discussed, practical results are also given. These devices were used to analyze
      the enantiomeric excess in biotransformation processes and for thermal
      immunoanalysis. In addition, the biosensors were applied for the monitoring and
      control of an L-ornithine producing process and for the application in
      hemodialysis monitoring. A review section discusses the use of thermal biosensors
      for monitoring biotechnological processes in general.

PMID- 9933976
TI  - Investigation of catalytic properties of immobilized enzymes and cells by flow
      microcalorimetry.
AB  - The investigation of catalytic properties of immobilized biocatalysts (IMB) is a
      time-consuming and not-always-simple procedure, requiring a simple and accurate
      method of enzyme-activity measurement. In comparison with generally-used
      techniques, flow microcalorimetry (FMC) has proven to be a very practical and
      versatile technique for direct monitoring of the course of enzyme reactions. The
      principal advantage of FMC is integration of the enzyme reaction and its
      monitoring in one step. This review summarizes the information needed for the
      complete kinetic or catalytic characterization of the IMB by FMC, without the
      requirement of any independent analytical method. The optimal experimental
      procedure is proposed. Examples of experimental studies on immobilized
      biocatalysts using the FMC are provided. The method is applicable to purified
      enzymes as well as to enzymes fixed in cells.

PMID- 9933977
TI  - Bioactive agents from natural sources: trends in discovery and application.
AB  - About 30% of the worldwide sales of drugs are based on natural products. Though
      recombinant proteins and peptides account for increasing sales rates, the
      superiority of low-molecular mass compounds in human diseases therapy remains
      undisputed mainly due to more favorable compliance and bioavailability
      properties. In the past, new therapeutic approaches often derived from natural
      products. Numerous examples from medicine impressively demonstrate the innovative
      potential of natural compounds and their impact on progress in drug discovery and
      development. However, natural products are currently undergoing a phase of
      reduced attention in drug discovery because of the enormous effort which is
      necessary to isolate the active principles and to elucidate their structures. To
      meet the demand of several hundred thousands of test samples that have to be
      submitted to high-throughput screening (HTS) new strategies in natural product
      chemistry are necessary in order to compete successfully with combinatorial
      chemistry. Today, pharmaceutical companies have to spend approximately US $350
      million to develop a new drug. Currently, approaches to improve and accelerate
      the joint drug discovery and development process are expected to arise mainly
      from innovation in drug target elucidation and lead finding. Breakthroughs in
      molecular biology, cell biology, and genetic engineering in the 1980 s gave
      access to understanding diseases on the molecular or on the gene level.
      Subsequently, constructing novel target directed screening assay systems of
      promising therapeutic significance, automation, and miniaturization resulted in
      HTS approaches changing the industrial drug discovery process drastically.
      Furthermore, elucidation of the human genome will provide access to a
      dramatically increased number of new potential drug targets that have to be
      evaluated for drug discovery. HTS enables the testing of an increasing number of
      samples. Therefore, new concepts to generate large compound collections with
      improved structural diversity are desirable.

PMID- 9933978
TI  - Protein glycosylation: implications for in vivo functions and therapeutic
      applications.
AB  - The glycosylation machinery in eukaryotic cells is available to all proteins that
      enter the secretory pathway. There is a growing interest in diseases caused by
      defective glycosylation, and in therapeutic glycoproteins produced through
      recombinant DNA technology route. The choice of a bioprocess for commercial
      production of recombinant glycoprotein is determined by a variety of factors,
      such as intrinsic biological properties of the protein being expressed and the
      purpose for which it is intended, and also the economic target. This review
      summarizes recent development and understanding related to synthesis of glycans,
      their functions, diseases, and various expression systems and characterization of
      glycans. The second section covers processing of N- and O-glycans and the factors
      that regulate protein glycosylation. The third section deals with in vivo
      functions of protein glycosylation, which includes protein folding and stability,
      receptor functioning, cell adhesion and signal transduction. Malfunctioning of
      glycosylation machinery and the resultant diseases are the subject of the fourth
      section. The next section covers the various expression systems exploited for the
      glycoproteins: it includes yeasts, mammalian cells, insect cells, plants and an
      amoeboid organism. Biopharmaceutical properties of therapeutic proteins are
      discussed in the sixth section. In vitro protein glycosylation and the
      characterization of glycan structures are the subject matters for the last two
      sections, respectively.

PMID- 9933979
TI  - Bioaffinity based immobilization of enzymes.
AB  - Procedures that utilize the affinities of biomolecules and ligands for the
      immobilization of enzymes are gaining increasing acceptance in the construction
      of sensitive enzyme-based analytical devices as well as for other applications.
      The strong affinity of polyclonal/monoclonal antibodies for specific enzymes and
      those of lectins for glycoenzymes bearing appropriate oligosaccharides have been
      generally employed for the purpose. Potential of affinity pairs like cellulose
      cellulose binding domain bearing enzymes and immobilized metal ionsurface
      histidine bearing enzymes has also been recognised. The bioaffinity based
      immobilization procedures usually yield preparations exhibiting high catalytic
      activity and improved stability against denaturation. Bioaffinity based
      immobilizations are usually reversible facilitating the reuse of support matrix,
      orient the enzymes favourably and offer the possibility of enzyme immobilization
      directly from partially pure enzyme preparations or even cell lysates. Enzyme
      lacking innate ability to bind to various affinity supports can be made to bind
      to them by chemically or genetically linking the enzymes with appropriate
      polypeptides/domains like the cellulose binding domain, protein A, histidine-rich
      peptides, single chain antibodies, etc.

PMID- 9933980
TI  - Biocatalytic asymmetric decarboxylation.
AB  - Biocatalytic decarboxylation is a unique reaction, in the sense that it can be
      considered to be a protonation reaction to a "carbanion equivalent" intermediate
      in aqueous medium. Thus, if optically active compounds can be prepared via this
      type of reaction, it would be a very characteristic biotransformation, as
      compared to ordinary organic reactions. An enzyme isolated from a specific strain
      of Alcaligenes bronchisepticus catalyzes the asymmetric decarboxylation of alpha
      aryl-alpha-methylmalonic acid to give optically active alpha-arylpropionic acids.
      The effect of additives revealed that this enzyme requires no biotin, no co
      enzyme A, and no ATP, as ordinary decarboxylases and transcarboxylases do.
      Studies on inhibitors of this enzyme and spectroscopic analysis made it clear
      that the Cys residue plays an essential role in the present reaction. The unique
      reaction mechanism based on these results and kinetic data in its support are
      presented.

PMID- 9933981
TI  - Stereoinversions using microbial redox-reactions.
AB  - This paper aims to provide a summary of the recent literature on the use of redox
      enzymes to carry out stereoinversion reactions on chiral secondary alcohols.
      Emphasis has been placed on biotransformations which result in the deracemization
      of a racemic substrate to give high value synthetic intermediates in a
      theoretical 100% yield. Most of the biocatalysts which are competent to carry out
      such transformations are whole cell systems, which contain the necessary cofactor
      recycling machinery to facilitate this otherwise entropically disfavoured
      process. The first section deals with deracemization of compounds such as
      mandelic acid and pantoyl lactone using two microorganisms which display
      enantiocomplementary stereospecificity. The deracemization of chiral alcohols
      such as beta-hydroxyesters, aryl ethanols and terminal 1,2-diols with single
      microorganisms will then be discussed and the influence of growth and reaction
      conditions on the selectivity observed will be emphasised. Then the ability of
      several microorganisms to deracemize by double stereoinversion substrates with
      two stereocentres such as cyclohexan-1,2-diol, cis and trans indan-1,2-diol and
      pentan-2,4-diol will be presented and some mechanistic rationale proposed. Lastly
      enzymes known as epimerases which are important in sugar and deoxysugar
      biosynthesis will be discussed with reference to some recent work on the
      mechanism of UDP-glucose epimerase.

PMID- 9933982
TI  - Biotransformations with peroxidases.
AB  - Enzymes are chiral catalysts and are able to produce optically active molecules
      from prochiral or racemic substrates by catalytic asymmetric induction. One of
      the major challenges in organic synthesis is the development of environmentally
      acceptable chemical processes for the preparation of enantiomerically pure
      compounds, which are of increasing importance as pharmaceuticals and
      agrochemicals. Enzymes meet this challenge! For example, a variety of peroxidases
      effectively catalyze numerous selective oxidations of electron-rich substrates,
      which include the hydroxylation of arenes, the oxyfunctionalizations of phenols
      and aromatic amines, the epoxidation and halogenation of olefins, the oxygenation
      of heteroatoms and the enantioselective reduction of racemic hydroperoxides. In
      this review, we summarize the important advances achieved in the last few years
      on peroxidase-catalyzed transformations, with major emphasis on preparative
      applications.

PMID- 9933983
TI  - Production of chiral C3- and C4-units by microbial enzymes.
AB  - Enzyme (biocatalysis) reactions display far greater specificities, such as
      substrate specificity, stereospecificity, regiospecificity and so on, than more
      conventional forms of organic reactions. Using these specificities of the
      enzymes, many useful compounds have been enzymatically produced. Compounds
      possessing C3- and C4-units with additional functional groups are promising
      materials for the synthesis of various useful compounds. In particular, optically
      active C3- and C4-synthetic units are quite important intermediates for the
      preparation of pharmaceuticals and fine chemicals. Microbial transformation with
      enzymes showing stereo-specificities have been applied to the asymmetric
      synthesis of optically active substances. In this article the recent works on the
      practical production of chiral C3- and C4-synthetic units with microbial enzymes
      are described.

PMID- 9933984
TI  - Epoxide hydrolases and their synthetic applications.
AB  - Chiral epoxides and 1,2-diols, which are central building blocks for the
      asymmetric synthesis of bioactive compounds, can be obtained by using enzymes-
      i.e. epoxide hydrolases--which catalyse the enantioselective hydrolysis of
      epoxides. These biocatalysis have recently been found to be more widely
      distributed in fungi and bacteria than previously expected. Sufficient sources
      from bacteria, such as Rhodococcus and Nocardia spp., or fungi, as for instance
      Aspergillus and Beauveria spp., have now been identified. The reaction proceeds
      via an SN2-specific opening of the epoxide, leading to the formation of the
      corresponding trans-configured 1,2-diol. For the resolution of racemic
      monosubstituted and 2,2- or 2,3-disubstituted substrates, various fungi and
      bacteria have been shown to possess excellent enantioselectivities. Additionally,
      different methods, which lead to the formation of the optically pure product diol
      in a chemical yield far beyond the 50% mark (which is intrinsic to classic
      kinetic resolutions), are discussed. In addition, the use of non-natural
      nucleophiles such as azides or amines provides access to enantiomerically
      enriched vicinal azido- and amino-alcohols. The synthetic potential of these
      enzymes for asymmetric synthesis is illustrated with recent examples, describing
      the preparation of some biologically active molecules.

PMID- 9933985
TI  - Microbial models for drug metabolism.
AB  - This review describes microbial transformation studies of drugs, comparing them
      with the corresponding metabolism in animal systems, and providing technical
      methods for developing microbial models. Emphasis is laid on the potential for
      selected microorganisms to mimic all patterns of mammalian biotransformations and
      to provide preparative methods for structural identification and toxicological
      and pharmacological studies of drug metabolites.

PMID- 9933986
TI  - Natural products as angiogenesis inhibitors.
AB  - Angiogenesis is a strictly controlled process in the healthy, adult human body.
      It is regulated by a variety of endogenous angiogenic and angiostatic factors. It
      is only switched on, e.g., during wound healing. Pathological angiogenesis
      occurs, for example, in cancer, chronic inflammation, or atherosclerosis.
      Angiogenesis inhibitors are able to interfere with various steps of angiogenesis,
      like basement destruction of blood vessels, proliferation and migration of
      endothelial cells, or the lumen formation. Among the known angiogenesis
      inhibitors compounds derived from natural sources, like flavonoids, sulphated
      carbohydrates, or triterpenoids are playing a prominent role.

PMID- 9933987
TI  - Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on
      intestinal bacterial hydrolyzing potential and significance of treatment with an
      active bacterial metabolite.
AB  - The antimetastatic effects of orally administered ginsenoside Rb1 (Rb1) and an
      active metabolite by intestinal bacteria, 20-O-beta-D-glucopyranosyl-20(S)
      protopanaxadiol (I), were studied, by using a spontaneous metastasis model
      produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic
      C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by
      intestinal bacteria) was first done and the data found were positively correlated
      to the antimetastatic effect of Rb1 through the medium of I. The transformation
      rate by 41% fecal specimens was less than 10% and consecutive Ginseng
      administrations were ineffective for the mice with hydrolyzing potential of less
      than 10%, which limited the antimetastatic efficacy of Rb1- In contrast, the
      efficacy of I was greater than that of Rb1 and at least comparable to that of S
      FU. No effect of I on the primary tumor growth was found, indicating a specific
      antimetastatic activity. In a leg amputation model with the LLC-line, an effect
      on survival time of I (8 mg/kg/day) equal to that of 5-FU (10 mg/kg/day) was seen
      and 38% mice were cured as compared with 13% cured by amputation alone. These
      findings suggest that the active drug is the bacterial metabolite I which should
      be administered rather than Rb1.

PMID- 9933988
TI  - Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human endothelial
      cells to release a lymphocyte-proliferation-regulating factor.
AB  - In the present study we show that pentacyclic but not tetracyclic oxindole
      alkaloids from Uncoria tomentosa (Willd.) DC. (Rubiaceae) induced EA.hy926
      endothelial cells to release some yet to be determined factor(s) into the
      supernatant; this factor was shown to significantly enhance proliferation of
      normal human resting or weakly activated B and T lymphocytes. In contrast,
      proliferation of normal human lymphoblasts and of both the human lymphoblastoid B
      cell line Raji and the human lymphoblastoid T cell line Jurkat was inhibited
      significantly while cell viability was not affected. Tetracyclic oxindole
      alkaloids dose-dependently reduce the activity of pentacyclic oxindole alkaloids
      on human endothelial cells.

PMID- 9933989
TI  - A sensitive and quick microplate method to determine the minimal inhibitory
      concentration of plant extracts for bacteria.
AB  - Agar diffusion techniques are used widely to assay plant extracts for
      antimicrobial activity, but there are problems associated with this technique. A
      micro-dilution technique was developed using 96-well microplates and tetrazolium
      salts to indicate bacterial growth. p-Iodonitrotetrazolium violet [0.2 mg/ml]
      gave better results than tetrazolium red or thiazolyl blue. The method is quick,
      worked well with Staphylococcus aureus, Enterococcus faecalis, Pseudomonas
      aeruginosa, and Escherichia coli and with non-aqueous extracts from many
      different plants. The method gave reproducible results; required only 10-25
      microliters of extract to determine minimal inhibitory concentrations,
      distinguished between microcidal and microstatic effects, and provided a
      permanent record of the results. Using S. aureus, and a Combretum molle extract,
      the technique was 32 times more sensitive than agar diffusion techniques and was
      not sensitive to culture age of the test organism up to 24 hours. The S. aureus
      culture could be stored up to 10 days in a cold room with little effect on the
      assay results. This method was useful in screening plants for antimicrobial
      activity and for the bioassay-guided isolation of antimicrobial compounds from
      plants. MIC values determined for sulfisoxazole, norfloxacin, gentamicin, and
      nitrofuratoin were similar to values indicated in the literature but values
      obtained with trimethroprim and ampicillin were higher with some bacteria.

PMID- 9933990
TI  - Intestinal immune system modulating polysaccharides from rhizomes of Atractylodes
      lancea.
AB  - Hot water extract (ALR-0) of rhizomes of Atractylodes lanceo DC. was fractionated
      into MeOH-soluble fraction (ALR-1), supernatant fraction of EtOH precipitation
      (ALR-3 + 4), and crude polysaccharide fraction (ALR-5). Among these fractions,
      only ALR-5 showed potent stimulating activity for proliferation of bone marrow
      cells mediated by Peyer's patch cells. ALR-5 gave three potently active
      carbohydrate-rich fractions (ALR-5IIa, 5IIb, and 5IIc) by anion-exchange
      chromatography on DEAE-Sepharose CL-6B, and three active polysaccharides (ALR
      5IIa-1-1, ALR-5IIb-2-2, and ALR-5IIc-3-1) were further purified from the
      respective fractions. The order of activity was revealed to be ALR-5IIb-2-2 > or
      = ALR-5IIa-1-1 > ALR-5IIc-3-1, ALR-5IIa-1-1, 5IIb-2-2, and 5IIc-3-1 each was
      eluted as a single peak on HPLC and their molecular weights were estimated to be
      74,000, 3,100, 16,000, respectively. ALR-5IIa-1-1 consisted mainly of Ara and Gal
      (molar ratio; 0.6: 1.0) in addition to a trace amount of uronic acid whereas ALR
      5IIb-2-2 and ALR-5IIc-3-1 mainly comprised Ara, Gal, GlcA, and GalA (molar ratio;
      0.2: 1.0: 0.2: 0.8, and 0.5: 1.0: 0.7: 1.5, respectively). Methylation analysis
      indicated that ALR-5IIa-1-1 consisted mainly of terminal Araf, 4- or 5-linked
      Ara, 3.4- or 3.5-branched Ara, and 3-linked, 4-linked, and 3,6-branched Gal. ALR
      5IIb-2-2 and ALR-5IIc-3-1 were composed mainly of terminal Araf, 4- or 5-linked
      Ara, 4-linked Gal, 4-linked GalA, and terminal GlcA. In addition, ALR-5IIb-2-2
      mainly comprised 4-linked Xyl whereas ALR-5IIc-3-1 consisted mainly of 2,4
      branched Rha. Single radial gel diffusion indicated that ALR-5IIa-1-1 showed a
      strong reactivity with beta-glucosyl-Yariv antigen, whereas ALR-5IIb-2-2 and ALR
      5IIc-3-1 did not show the reactivity with the antigen. Treatments of ALR-5IIa
      with NalO4, NaClO2 and pronase did not reduce the stimulating activity for
      Peyer's patch cells, however combination of exo-alpha-L-arabinofuranosidase and
      exo-beta-D-(1-->3)-galactanase digestions of ALR-5IIa-1-1 significantly decreased
      its activity.

PMID- 9933991
TI  - Antimicrobial flavonoids from Glycyrrhiza glabra hairy root cultures.
AB  - A new compound named licoagrodione was isolated from the hairy root cultures of
      Glycyrrhiza glabra (Fabaceae) together with five known prenylated flavonoids. The
      structure of licoagrodione has been elucidated on the basis of spectral evidence
      and it was found to have antimicrobial activity indicated by disc diffusion
      method.

PMID- 9933992
TI  - Structure-activity relationships of protoberberines having antimicrobial
      activity.
AB  - 13-Alkyl derivatives (2-6 and 8-12) of berberine (1) and palmatine (7) were
      subjected to in vitro antibacterial activity tests against Bacillus subtilis and
      Salmonella enteritidis. Antibacterial activity increased as the length of the C
      13 aliphatic side chain increased. The effects of the oxygen-substituents on
      aromatic rings A, C, and D of protoberberinium salts 13-20 on the antimicrobial
      activity against Staphylococcus aureus, B. subtilis, S. enteritidis, Escherichia
      coli, and Candida albicans are also discussed. The change in lipophilicity of the
      protoberberinium salts caused by modification of the substituents appears to
      influence the antibacterial activity. 13-Hexylberberine (6) and 13-hexylpalmatine
      (12) exhibited the greatest antibacterial activity.

PMID- 9933993
TI  - Cytotoxic sesquiterpene lactones from Inula britannica.
AB  - Cytotoxicity-guided fractionation of the flowers of Inula britannica led to the
      isolation of four sesquiterpene lactones, 4 alpha, 6 alpha-dihydroxyeudesman-8
      beta, 12-olide (1), ergolide (2), 8-epi-helenalin (3), and bigelovin (4).
      Compound 1 was isolated as a new natural product. These compounds showed
      cytotoxicity against human tumor cell lines.

PMID- 9933994
TI  - Cytotoxicity and antiviral activity of the compounds from Euphorbia kansui.
AB  - Eleven compounds including four triterpenes, one sterol, and six diterpenes from
      E kansui had been assayed for their cytotoxicity and activiral activity. The
      relations between structures and bioactivities have also been noted.

PMID- 9933995
TI  - Mechanism of the aortic relaxation induced by low concentrations of berberine.
AB  - The mechanism of the aortic relaxation induced by a low concentration of
      berberine was investigated in rat isolated aorta. It was found that the aortic
      relaxation induced by berberine below 1 x 10(-6) M was solely endothelium
      dependent. Denuded aorta and methylene blue pretreated aorta did not demonstrate
      aortic relaxation with such berberine concentrations. Higher concentrations
      (above 1 x 10(-6) M berberine), however, induced aortic relaxation irrespective
      of the presence of intact endothelium or methylene blue pretreatment. Since
      methylene blue is known as a direct inhibitor of nitric oxide synthase beside
      being a nonspecific guanylyl cyclase inhibitor, the present data suggest that the
      mechanism of the aortic relaxation induced by a low berberine concentration is
      solely dependent on the presence of endothelium.

PMID- 9933996
TI  - Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and
      Chelidonium majus extracts on isolated guinea-pig ileum.
AB  - Two ethanolic dry extracts from the herb Chelidonium majus L. with a defined
      content of the main alkaloids (chelidonine, protopine, and coptisisine) and the
      alkaloids themselves were studied in three different antispasmodic test models on
      isolated ileum of guinea-pigs. In the BaCl2-stimulated ileum, chelidonine and
      protopine exhibited the known papaverine-like musculotropic action, whereas
      coptisine (up to 3.0 x 10(-5) g/ml) was ineffective in this model. Both extracts
      were active with 53.5% and 49.0% relaxation at 5 x 10(-4) g/ml. The carbachol and
      the electric field stimulated contractions were antagonized by all three
      alkaloids. Coptisine showed competitive antagonist behaviour with a pA2 value of
      5.95. Chelidonine and protopine exhibited a certain degree of non-competitive
      antagonism. In the electric field the antagonist activities decreased in the
      order protopine > coptisine > chelidonine. The concentrations of the chelidonium
      herb extracts for 50% inhibition of the carbachol and electrical field induced
      spasms were in the range of 2.5 to 5 x 10(-4) g/ml.

PMID- 9933997
TI  - Pinocembrin chalcone: an antibacterial compound from Helichrysum trilineatum.

PMID- 9933998
TI  - Chemical components and anti-inflammatory activity from Bidens subalternans.

PMID- 9933999
TI  - Glucuronidation of naringenin in rats.

PMID- 9934000
TI  - A workplace breast cancer screening program. Costs and components.
AB  - Screening for breast cancer can result in early detection of malignancies and
      lives saved. Many employers now offer periodic screening as an employee health
      benefit, and some have established screening programs in the workplace. This
      study was performed to identify the employer costs of breast cancer screening in
      the workplace, referrals for suspicious findings, and initial treatment of
      malignant disease. Additionally, the costs for these same services, had they been
      obtained outside of a workplace screening program, were estimated. Data on
      program components and associated costs for an established employer based breast
      cancer screening program were obtained. These costs were compared to those among
      a hypothetical cohort of women not enrolled in the workplace screening program.
      From 1989 through 1995, 1,416 women participated in the program. Nearly 2,500
      screening mammograms and approximately 2,773 clinical breast examinations were
      performed, resulting in 292 referrals to physicians outside of the program for
      additional diagnostic procedures and treatment as needed. These referrals
      resulted in the detection of 12 malignancies: 8 Stage I; 3 Stage II; and 1 Stage
      III. Mammographic and clinical breast examination screening cost $249,041;
      referrals resulting in benign disease or no detectable disease cost $185,002; and
      referrals resulting in malignant disease, followed by initial treatment, cost
      $148,530. Therefore, the total cost was $582,573. Approximately 47% of the cost
      of referrals and initial treatment were due to employee lost productivity. Total
      cost in the hypothetical cohort was $1,067,948 under the assumptions that all
      women received screening outside of the workplace, and that the same number of
      malignancies were detected at the same stage as in the workplace program. These
      findings indicate referrals resulting in detection of benign disease or no
      disease accounted for a substantial proportion of the total cost of the program.
      In addition, employee lost productivity accounted for almost 50% of the cost of
      all referrals and initial treatment. Workplace screening is a relatively
      efficient approach for early detection of breast cancer when compared to off site
      screening or no screening. The efficiency could be improved with a reduction in
      the number and cost of unnecessary referrals.

PMID- 9934001
TI  - Repositioning a slumped person in a wheelchair. A biomechanical analysis of three
      transfer techniques.
AB  - The purpose of this study was to determine the effect of three lifting techniques
      (unassisted lift, vertically assisted lift, and horizontally assisted lift) and
      two patient masses (65 kg and 75 kg) on loads acting on the lifter's spine when
      repositioning a wheelchair bound patient to a more upright sitting position. A
      static biomechanical model was used in conjunction with ground reaction force and
      videographic data to estimate compression and shear forces at the lumbosacral
      (L5/S1) joint. Results indicated that: L5/S1 compression forces associated with
      both unassisted and assisted transfers were of sufficient magnitude to warrant
      mechanical assistance; the two person technique with the assistant pushing the
      legs toward the back of the chair was associated with the lowest spinal loads;
      and L5/S1 compression forces were significantly greater for the vertically
      assisted lift compared to the unassisted lift. If a manual transfer is to be
      performed, the horizontally assisted lift is recommended to minimize loads on the
      lumbar spine of the lifter.

PMID- 9934002
TI  - Silicone breast implants. An argument for science.

PMID- 9934003
TI  - Defining the scope of occupational health services. Effective policy and
      procedure development.

PMID- 9934004
TI  - Ten tips for becoming "indispensable".

PMID- 9934005
TI  - Using basic search tools on the Internet.

PMID- 9934006
TI  - HCFA's final rule on Medicare brings good news for NPs.

PMID- 9934007
TI  - Is it ever too late to pursue a dream?

PMID- 9934008
TI  - Making 'watermarks'. Professional achievements in 1998.

PMID- 9934009
TI  - Cure for cancer? AIDS vaccine? Not just yet....

PMID- 9934010
TI  - The blockbuster drugs of 1998.

PMID- 9934011
TI  - Getting a healthy start feeding. Issues in the first year of life.

PMID- 9934012
TI  - Between childbearing & menopause. Contraceptive options for women over 40.

PMID- 9934014
TI  - Getting to know David Satcher, MD, PhD. Interview by Michael Gerchufsky.

PMID- 9934013
TI  - Gestational diabetes. A screening and management update.

PMID- 9934015
TI  - Tuberculosis in long-term care settings. Are you prepared?

PMID- 9934016
TI  - What about Dillon?

PMID- 9934017
TI  - Beating the January "blahs".

PMID- 9934018
TI  - Reforming managed care. Carving out women's rights in health care.

PMID- 9934019
TI  - Intrapartum fetal oxygen saturation monitoring. Ongoing clinical research
      explores partnering new method with EFM.

PMID- 9934020
TI  - Male patients for WHNPs. Treating women and their partners expands clinical
      scope.

PMID- 9934021
TI  - Predicting breastfeeding problems. These tools may--or may not--help assess high
      risk mother-baby couples.

PMID- 9934022
TI  - Finding good information on the WWW. These quick tips will help you sort trash
      from treasure.

PMID- 9934023
TI  - Negotiation skills every nurse needs.

PMID- 9934025
TI  - Laughlines. Finding humor in our workplace.

PMID- 9934024
TI  - Labor induction & augmentation. Knowing when, and how, to assist women in labor.

PMID- 9934026
TI  - Care of elderly people in hospital is inadequate.

PMID- 9934027
TI  - Healthcare litigation protocols under review.

PMID- 9934028
TI  - TenderWet: an innovation in moist wound healing.
AB  - The use of moisture-retentive dressings (dressings that are capable of
      maintaining a warm moist environment) has been shown to provide the optimal
      environment for wound healing, accelerating the healing process and promoting
      tissue growth. TenderWet, produced by Paul Hartmann, is an innovative dressing
      that not only provides a moist warm environment but also incorporates the unique
      properties of Ringer's solution which actively cleanses (debrides) the wound.

PMID- 9934029
TI  - Obtaining the evidence for clinically effective wound care.
AB  - In tissue viability, as in other aspects of health care, there is increasing
      recognition of the need for healthcare interventions to be supported by good
      research evidence. The randomized controlled trial (RCT) is considered to provide
      the most accurate evidence of effectiveness. This article discusses some of the
      problems that arise when researchers attempt to obtain the relevant evidence.
      They include funding, sample selection, sample size, recruitment of patients, and
      mortality and attrition rates. These points are illustrated by means of a case
      study. In this study an RCT was undertaken to compare two dressings for the
      management of pressure sores. Problems arose with recruitment of patients to the
      study. Relevant issues associated with this are discussed and recommendations for
      future recruitment are presented.

PMID- 9934030
TI  - Interventions for confusion and dementia. 4: Alternative approaches.
AB  - While reality orientation and reminiscence are useful therapies, recent years
      have been a growing awareness of other approaches to caring for people with
      dementia. This article discusses some of the less established, but potentially
      valuable, approaches--validation therapy, resolution therapy and multisensory
      environments. Validation therapy seeks to help care givers understand the
      thoughts and feelings of care receivers. In contrast to the confrontational
      approach of reality orientation, it encourages empathy between giver and
      receiver. Resolution therapy develops aspects of validation therapy, adopting a
      less structured, more psychodynamic and individualistic approach. Multisensory
      environments use sensory stimulation to achieve pleasure for the individual. All
      three approaches have a limited knowledge base, but share a humanistic philosophy
      that enables them to contribute to a person's quality of life.

PMID- 9934031
TI  - Promoting compliance with antihypertensive medication.
AB  - One of the key areas identified for action in 'The Health of the Nation'
      (Department of Health, 1992) is a reduction in the number of deaths from
      cerebrovascular accident. The major precursor of stroke is elevated blood
      pressure, and although efficacious medication exists for the control of
      hypertension, non-compliance in patients with this condition is notoriously high.
      This article examines ways to successfully address this problem and reduce
      morbidity. Consideration of psychosocial variables emphasizes that compliance
      with antihypertensive medication regimens is a multifactorial problem, but one
      that can be solved. Nurses, mindful of barriers to compliance, can encourage and
      support the patient in taking the prescribed antihypertensive medication.

PMID- 9934032
TI  - Falls in elderly people: is the risk suitably assessed?
AB  - Results of the annual screening of people over the age of 75 years were used to
      determine whether the risk of falling in this age group is adequately assessed.
      The study group comprised primary healthcare professionals employed within six
      counties throughout England and Wales. Three per cent of respondents indicated
      that they use formal risk assessment tools when undertaking screening of people
      over 75 years. Analysis of the answers provided by these respondents, and of
      their assessment tools used, indicates that none of the tools are suitable for
      identifying those people at risk of falling within the home environment. Ninety
      seven per cent of respondents indicated that they did not use a formal risk
      assessment tool for this age group. Analysis of the data provided by these
      respondents identified that the information gathered did suitably identify those
      people at risk of falling within the home.

PMID- 9934033
TI  - Discharge planning: establishing an effective coordination team.
AB  - This article investigates the developing role of the discharge coordinator and
      explores how safe, effective and timely discharge from hospital can be achieved.
      In January 1996, a team of four discharge coordinators were jointly appointed by
      the King's Healthcare NHS Trust in partnership with the local social services
      department. The coordinators were appointed to work with the multidisciplinary
      teams to improve trustwide discharge planning practice. The team focused on six
      core objectives: central coordination, open interagency communication, continuing
      education, patient advocacy, information resource and audit of discharges.
      Despite the ward staff's early difficulties regarding the nature of the role, the
      team did begin to collaborate effectively when working alongside all members of
      the multidisciplinary team and with patients and families.

PMID- 9934034
TI  - Transcultural therapy. 2: Mental health and learning disabilities.
AB  - The first article in this two-part series (Vol 7(15): 901-6) examined the issues
      surrounding healthcare provision in the context of the UK as a multicultural
      society in relation to mental health and learning disabilities. This second
      article considers the development of psychotherapy, theory and skills of working
      in terms of its impact and influence upon the education and practice of community
      mental health nurses and community nurses in learning disability within the UK.
      The major schools of influence in psychology will be examined in relation to
      their limitations for practice with clients from various cultures. In addition,
      three multicultural models of counselling which address cultural diversity will
      be appraised. Finally, the need for educational systems and service providers to
      foster and develop positive cultural attitudes among nurse practitioners will be
      emphasized. Both individual practitioners and employment organizations will need
      to be much more responsive and committed to developing multicultural services as
      we approach the millennium.

PMID- 9934035
TI  - Evidence-based care: can we overcome the barriers?
AB  - Evidence-based care has become the new mantra within the NHS, despite the fact
      that the concept of applying research to practice has been promoted for several
      decades. However, literature on the subject suggests that formidable obstacles
      remain to the integration of research into care delivery. This article describes
      a study which used Funk et al's (1991a,b) Barriers Scale with a population of
      nurses in a large teaching hospital in the UK. This scale was specifically
      developed to identify barriers to the introduction of research into practice, and
      modified for a UK context. The results suggest that a complex array of barriers
      exist but that foremost among these is the nature of the organizations within
      which nurses work. Comparisons are made with data from the USA, and the need to
      create time for nurses to implement change, and to empower them to do so, is
      stressed.

PMID- 9934036
TI  - The value of prayer in modern-day nursing.

PMID- 9934037
TI  - Patient information.

PMID- 9934038
TI  - Parents in recovery: a paediatric recovery nurse's view.

PMID- 9934039
TI  - NATN/3M Award. Telephone logging and walk-in clinic.

PMID- 9934040
TI  - Day surgery: improving care through follow up contact.
AB  - In this article I will outline the method of evidence based practice we have
      implemented during the last three years following the introduction of day surgery
      as a specific speciality in our Trust. I will outline the method of accessing
      information on a regular basis and how this information was used to improve the
      service we offer. Finally I will suggest how, as a group of professionals, we may
      take this initiative forward towards AD 2000.

PMID- 9934041
TI  - Celebrating partnerships in perioperative care

PMID- 9934042
TI  - Ethnic and cultural awareness.

PMID- 9934043
TI  - Preoperative information-giving: an essential element of perioperative practice.
AB  - The aim of this article is to review the literature pertaining to the
      perioperative nursing activity of information-giving. The relationship between
      anxiety, coping strategies and information giving will be discussed, with further
      consideration of how informational care is affected by the nurse-patient
      relationship. Inter-related concepts of information giving will be explored as
      the article develops.

PMID- 9934044
TI  - The history and application of acupuncture.

PMID- 9934046
TI  - Frequency of cerebrovascular accident after cardiac surgery.

PMID- 9934045
TI  - Alternative and complementary therapies: treading tentatively out of the
      mainstream.

PMID- 9934047
TI  - Research utilization and improvement in outcomes after diagnostic cardiac
      catheterization.
AB  - This research utilization project helped summarize the research basis of current
      practice related to duration of bed rest after cardiac catheterization via the
      femoral artery. Several physicians have changed their practice as a result of
      this project, and the safety of patients is being maintained. Interestingly, De
      Jong and Morton recently published a research analysis of interventions used to
      control vascular complications after cardiac catheterization. These authors
      concluded from the review of the literature on duration of bed rest that evidence
      was sufficient to support a change in practice. Because we thought that the
      published evidence was insufficient to be used as the sole basis for a change in
      practice, we continued to follow the Iowa model. Specifically, we integrated
      scientific principles and expert recommendations with the published research
      base; recommended a change in practice; and monitored patients' outcomes, which
      ultimately did confirm the recommendations of De Jong and Morton. We are
      convinced that the combination of data from our own patients and the review of
      the literature was helpful to assure our medical and nursing staff that this
      change in practice was safe. This project illustrates the benefit of using the
      Iowa Model for Research Based Practice to Promote Quality Care as a guide to
      improve patients' outcomes.

PMID- 9934048
TI  - Care of patients with an indwelling pericardial catheter.

PMID- 9934049
TI  - Providing a critical care experience for undergraduate nursing students.

PMID- 9934050
TI  - Clinical aromatherapy and touch: complementary therapies for nursing practice.

PMID- 9934052
TI  - Public policy: a new paradigm grows from grass roots. Interview by Alison
      Paladichuk.

PMID- 9934051
TI  - Toward a standard of care for parents of infants in the neonatal intensive care
      unit.

PMID- 9934053
TI  - Pain management in the critically ill.

PMID- 9934054
TI  - Shivering in patients recovering from CABG.

PMID- 9934055
TI  - How healthy are critical care nurses?

PMID- 9934056
TI  - [Awakening of intensive care patients after prolonged continuous sedation].
AB  - A study was made of the degree of orientation, cooperation, and anxiety of
      patients admitted to the Intensive Care Unit of the Hospital de la Santa Creu i
      Sant Pau (level III), at the conclusion of prolonged continuous sedation.
      Recovery time was evaluated, understood as the time required to achieve
      orientation in time, place, and person. The study was descriptive. An analysis
      was made of 37 patients who met inclusion criteria between July 1995 and March
      1996. After discontinuing sedation, the Glasgow assessment was carried out
      (modified by Cook and Palma) every four hours until a score of > or = 14 was
      obtained. From then on, the degree of anxiety, using the Hamilton scale, and
      cooperation and orientation, using our own scales, were evaluated four times a
      day. The assessment concluded when the patient was oriented in time, space, and
      person. We recorded age, sex, disease, disease severity, previous admissions,
      type of sedation, need for additional bolus injections, and the state of anxiety
      as perceived by family members. Mean age of patients was 65.1 +/- 13.3 years;
      81.1% were men. Respiratory disease was the most common pathology, mean SAPS was
      10.7 +/- 2.6, and the most frequently administered drug was midazolam (81%).
      Patients required an average of 15 hours (164-0) to awaken and tended to taken
      longer to awake with midazolam. Once the were awake, the required 10 hours (48-0)
      hours before the were completely oriented. The degree of anxiety was mild and
      cooperation was regular during all measurements. No relation was found between
      variables. Our results suggest that a care plan designed to shorten temporal
      disorientation and promote cooperation would improve the quality of awakening.

PMID- 9934057
TI  - [Quality of care in intensive care units. Retrospective study on long-term
      patients].
AB  - Nursing care must be evaluated in order to determine its effectiveness and
      identify deficiencies, which makes it possible to introduce corrective measures
      to optimize quality. The quality of care given to patients in our unit was
      evaluated with a retrospective analysis of 915 records in the Nursing Care Plan
      corresponding to 59 patients with a mean ICU stay of 15.5 days. Six areas of care
      and indicators of deficient practice were identified: orotracheal intubation:
      accidental disconnection, displacement, obstruction, and pressure sores on lips;
      arterial catheterization: accidental disconnection and obstruction; central
      venous catheterization: accidental disconnection and contamination; urinary
      catheterization: accidental disconnection and urinary bacteriology; nasogastric
      intubation: accidental disconnection, obstruction, and nasal pressure sores;
      conservation of skin integrity: presence of pressure sores, and prevention of
      falls from the bed or chair. The reference standards were taken from the
      published literature. The results show that airway care was adequate, although
      the frequency of pressure sores on the lip produced by orotracheal tubes was
      high. The indicators for following up the care of vascular and urinary catheters
      showed results similar to established standards. There was a high rate of
      nasogastric tube obstruction due to the administration of medication. Finally,
      the frequency of pressure sores was well below established standards and there
      were no accidental falls. It is concluded that the detection of areas in which
      care is deficient requires an analysis of relevant nursing activities so that
      corrective measures can be taken. This study is a useful baseline for future
      quality control.

PMID- 9934058
TI  - [Incidence of gastrointestinal complications during enteral feeding. Results of a
      protocol].
AB  - Enteral nutrition (EN) is a nutritional support technique that has been shown to
      be an effective alternative to total parenteral nutrition (TPN) in critical
      patients, unless absolute contraindications exist. This study quantified,
      evaluated and assessed tolerance of EN by critically ill patients and
      gastrointestinal (GI) complications secondary to EN. We compared continuous EN
      without interruption (WI) and EN with a 7-hour nightly rest (NR). Sixty-nine
      patients were assigned randomly to WI or NR. The complications observed were
      diarrhea, increased residue, vomiting and/or regurgitation, and constipation. The
      results disclosed no significant differences between the WI and NR groups for any
      variable measured. We conclude that the frequency of GI complications was no
      higher, as shown by the results of the EN protocol established in our unit, so we
      consider this to be an optimal system for artificial feeding of patients in the
      critical phase.

PMID- 9934060
TI  - [Description of the intensive care unit. Hospital de Leon (Leon)].

PMID- 9934059
TI  - [Descriptive study of infections caused by central venous catheters with
      peripheral insertion].
AB  - OBJECTIVE: To know the infection rate for central venous catheters inserted via a
      peripheral vein (CVCIPV), the microorganisms involved, and the incidence of
      complications derived from catheter infections. METHOD: A prospective study
      carried out in the ICU of the Hospital de la Princesa in 1997. Clinical and
      microbiological data were collected from all patients with CVCIPC. Cultures were
      made of the intravascular segment (semiquantitative-quantitative procedure) and
      blood if symptoms or signs of infection were observed. Data were recorded from 72
      catheters in 72 patients. RESULTS: Fifty-one (70.8%) catheters were cultured, of
      which 47 (92.15%) were sterile. Infection was associated with the catheter in 3
      cases (5.8%) and bacteremia, which was complicated by septic shock, was
      associated with the catheter in 1 case (1.4%). The microorganisms found were
      Serratia marcescens, Morganella morgani, and Staphylococcus epidermidis.
      CONCLUSION: Central venous catheterization via a peripheral vein had a low rate
      of infectious complications.

PMID- 9934061
TI  - [Continuing education and self evaluation. Review of knowledge of neurologic
      nursing].

PMID- 9934062
TI  - Creating an educational videotape.
AB  - Staff development and patient education coordinators are challenged to lead
      efforts to provide resources for patient education. One option to provide cost
      effective, quality education is the use of videotapes. In this article, the
      authors identify six advantages of video instruction and detail the steps to
      create an educational videotape.

PMID- 9934063
TI  - Critical thinking. Strategies for clinical practice.
AB  - Critical thinking is an elusive concept. As a profession, nursing has yet to
      accept a universal definition of critical thinking. Despite the lack of
      consensus, nurse leaders in academia and practice settings overwhelmingly agree
      that critical thinking is essential. It is clear, considering the healthcare
      environment, nurses need to use critical thinking as a process for decision
      making in the clinical arena. This article clarifies critical thinking in
      practice by illuminating the imperative role it plays. Suggestions for fostering
      critical thinking, including specific strategies, provide a framework for
      practice.

PMID- 9934064
TI  - Faculty and internships. A match made in heaven?
AB  - An internship program was developed for new graduate nurses hired in the critical
      care area. Program goals included facilitating growth and development of 21 newly
      graduated BSN nurses to prepare them to care for a critically ill adult. The
      program design included the support and guidance of university faculty for a 3
      month period. The program content included planned observational, didactic, and
      clinical precept experiences. Interns were evaluated according to clinical logs,
      didactic examinations, and preceptor assessments. At completion of the program,
      all interns were hired by the participating hospital. Two interns elected to take
      medical-surgical positions. The remaining interns accepted positions within the
      critical care and "step-down" areas.

PMID- 9934065
TI  - A consortium approach to intravenous certification.
AB  - Providing education for intravenous therapy without offering redundant courses is
      a concern for staff development educators. The consortium approach maximizes
      resources, provides a standard and consistent level of intravenous training, and
      provides a cost-effective remedy. Problems, solutions, and benefits to students,
      educators, and hospitals are described in this article. Emergent issues are also
      discussed.

PMID- 9934066
TI  - Documentation in the land of perfect charts. How to turn your frogs into princes.
AB  - In this article, the author describes an innovative approach to teaching adult
      learners. A theatrical atmosphere was used with medieval characters, music, and
      head gear. This class about documentation was designed to spur creativity, team
      work, and ultimate individual accountability.

PMID- 9934067
TI  - Role orientation in novice home healthcare nurses.
AB  - The focus of healthcare delivery continues to shift from hospital-based nursing
      practice to care in the community, which includes home health care. Many basic
      nursing education programs provide home healthcare clinical experiences for
      students. However, this may not be enough to assist nurses in achieving home
      health nursing competency. Most nurses recruited into home health care worked
      exclusively in hospitals. Many nurses are employed in a practice environment for
      which they lack the necessary education and skills. As the practice environment
      for the nurse changes, so does the role of the nurse. Nurses are having
      difficulty adjusting to changing roles and responsibilities. This cross-sectional
      research study was conducted to evaluate the extent that new home healthcare
      nurses understand their role. This study reveals that nurses employed in home
      health care for 24 months or less continue to have only a moderate degree of
      understanding of their new role. These data suggest that educators critically
      evaluate the effectiveness of orientation programs for novice home healthcare
      nurses.

PMID- 9934068
TI  - Grief support for nursing staff in the ICU.
AB  - Patient death is a stressful experience for the patient, family, and the
      healthcare team. Nurses-often have only informal resources for coping with the
      sadness and grief they might experience. Realizing the need for nursing grief
      support, a group of staff nurses from the intensive care unit formed a grief
      support group. Using information from the literature and critical incident stress
      debriefing, the group developed support interventions to aid intensive care unit
      staff after patient death.

PMID- 9934069
TI  - History of continuing nursing education in the United States.

PMID- 9934070
TI  - Arranging a clinical practicum in a health care facility.
AB  - Staff development educators and administrators collaborate frequently to
      establish clinical experiences for student nurses. This article outlines key
      elements to consider and a time line for planning practicums. Some tools are
      offered to assist in the process. Arranging a clinical practicum in a health care
      facility requires flexibility, negotiation, and attention to detail for both the
      school and the facility. A mutually beneficial affiliation flourishes in such a
      facilitative environment.

PMID- 9934071
TI  - National training for a new nurse staffing resource management methodology.
AB  - The Veterans Affairs (VA) nursing services has implemented a new resource
      management methodology for determining nurse staffing based on the expert
      judgment of panels of nurses. This article describes how two educators worked
      with a development task force to design and implement a national education
      program to prepare 172 individual health care facility coordinators to implement
      the methodology. The education program was based on a systems approach
      emphasizing data collection and analysis, consensus building and expert decision
      making. Two pilot programs were conducted and recommendations resulted in a
      series of 1 1/2-day training sessions conducted across the United States.

PMID- 9934072
TI  - Continuing nursing education: what resources do bedside nurses use?
AB  - Continuing nursing education (CNE) has traditionally been considered a formalized
      learning experience. However, the results of this study indicated nurses
      providing direct patient care in a tertiary care hospital seldom participate in
      such activities. The nursing staff do use a variety of resources, both material
      and personnel, to meet their immediate learning needs. Most of their CNE
      activities appear to be undertaken within their work environment. The results of
      this study provide nurse educators and managers insight into how they can augment
      "on-the-job" learning opportunities for staff nurses.

PMID- 9934073
TI  - Attitudes of upper division nursing students toward organ donation.
AB  - BACKGROUND: Attitudes of 28 upper division BSN students toward organ donation
      were explored in this pilot study. METHOD: The Organ Donor Attitude Questionnaire
      II-Student Version was distributed to a convenience sample of 56 BSN students,
      with 28 completed questionnaires returned. RESULTS: Ninety-six percent (n = 27)
      of participants "agree" to "strongly agree" with the basic concept of organ
      donation. A significant negative correlation (rpb(26) = -.60, p = .0007) was
      found between attitude toward organ donation and having signed the organ donation
      portion of one's driver's license. Increased knowledge of the subject was
      believed to be a major influence by slightly more than two thirds (67.8%; n = 19)
      of those surveyed. Although students demonstrated a lack of knowledge regarding
      organ donation (mean = 62.5, range 0 to 100), no significant correlation was
      found between knowledge level and selected variables or attitude. CONCLUSION: The
      results indicate that educational programs addressing donor identification and
      management would be beneficial if included in nursing education curricula and new
      graduate orientation.

PMID- 9934074
TI  - Determine discharge readiness for Phase I and phase II areas

PMID- 9934075
TI  - Preoperative evaluation of the pulmonary patient undergoing nonpulmonary surgery.
AB  - As the human population continues to live longer, patients with chronic pulmonary
      disease are increasingly presenting for surgical treatment. The influences of
      general anesthesia and an operative procedure are well known to negatively impact
      pulmonary gas exchange. Pulmonary-compromised patients are at high risk for the
      development of perioperative complications as a consequence of not only their
      pulmonary disease but of associated comorbid disease processes. Certain risk
      factors associated with preexisting pulmonary conditions are known to increase
      the likelihood of intraoperative or postoperative complications. Essential
      components in the comprehensive care of these patients are the identification of
      these high-risk patients and the implementation of an inclusive perianesthetic
      care regimen designed to decrease pulmonary complications. This article will
      familiarize the perianesthetic nurse with pertinent skills required to
      effectively assess and prepare patients with pulmonary disease for their upcoming
      surgery.

PMID- 9934076
TI  - Respiratory care protocols in postanesthesia care.
AB  - Respiratory care protocols have been developed for specific therapies that
      include the following: oxygen titration, weaning from mechanical ventilation,
      sampling arterial blood gases, managing bronchospasm and secretions, treating
      atelectasis, endotracheal extubation, and managing the postextubation airway.
      Although relatively little attention has been given to using protocols in
      postanesthesia care, this environment lends itself to applying protocols. In this
      context, studies have examined and support the use of protocols for titrating
      supplemental oxygen, weaning patients from mechanical ventilation, and sampling
      arterial blood gases. As with other previously mentioned respiratory protocols,
      these protocols have shown efficacy for improving allocation of respiratory care
      services, cost savings, and favorable clinical outcomes. On this basis, while
      recognizing the need for further studies, respiratory care protocols implemented
      by respiratory therapists can be beneficial in the postanesthesia care setting.

PMID- 9934077
TI  - Recent developments in respiratory care pharmacology.
AB  - Bronchoactive inhaled aerosol drugs target the respiratory tract directly and
      seek to minimize systemic exposure and reduce side effects. Common delivery
      devices such as the metered dose inhaler, the small volume nebulizer, or the dry
      powder inhaler each deliver approximately the same fraction of dose (10%) to the
      lungs, although their dose amounts are not equivalent. Major respiratory drug
      groups are reviewed, and include the beta-adrenergic and anticholinergic
      bronchodilators, mucolytic agents, corticosteroids, mediator antagonists, anti
      infective agents, and exogenous surfactants. New agents in each group are
      identified and briefly described, along with the clinical use and most commonly
      observed side effects for each class of drugs.

PMID- 9934078
TI  - Ventilatory management in the postanesthesia care unit.
AB  - Postoperative ventilatory depression is common in patients who have received
      intravenous and inhalational anesthetic agents. Prompt assessment and treatment
      of ventilatory depression are essential to minimize morbidity and mortality.

PMID- 9934079
TI  - Pulmonary rehabilitation and self-care after ambulatory surgery.
AB  - Over 30 million Americans are living with chronic lung disease in the United
      States. The long-term ongoing care required by these individuals is a major
      contributor to American health care costs. Clinicians caring for persons with
      chronic respiratory disease are faced with minimal time in which to prepare
      patients for adequate self-care abilities. Often times, the clinician may assume
      that all of the "bases have been covered." In reality, it is because this
      assumption is made that persons with chronic respiratory disease are often not
      receiving the full breadth of information that they need to increase their self
      care abilities and optimize their quality of life. This article prepares the
      perianesthesia clinician to ensure that the important tenets of self-care
      information are addressed for the person with overt and/or underlying chronic
      respiratory disease.

PMID- 9934081
TI  - [Practical training in crisis]

PMID- 9934080
TI  - Postoperative oxygen therapy.
AB  - Much has been published in the medical literature concerning adverse events
      relating to the surgical patient. Among the notable disorders requiring the
      expertise of the postanesthesia care unit nurse are the diagnosis and management
      of respiratory dysfunction acutely attributable to the effects of surgery and
      anesthesia. Inhalational and/or intravenous anesthetic agents contribute to
      pathophysiological alterations that lend to the development of hypoxemia in the
      postoperative period. When patients present with preexisting respiratory disease,
      their care is frequently more complex and challenging. This review session will
      address the oxygenation component of respiration and the perioperative influences
      that alter it as well as treatment considerations for normalizing oxygenation.

PMID- 9934082
TI  - [... and suddenly there is a crisis].

PMID- 9934083
TI  - [Psychiatry--societies sewage treatment].

PMID- 9934084
TI  - [Dying and death in the hospital. Very few are dying alone].

PMID- 9934085
TI  - [Remake of the Babylonian language confusion?].

PMID- 9934086
TI  - [Psychotherapy for the elderly. Arriving in paradise with a smile].

PMID- 9934087
TI  - [The difficulty of doing good].

PMID- 9934088
TI  - [Federal elections: no to the Drug Legislation initiative].

PMID- 9934089
TI  - [The essential role of the nurse caring for patients during cardiovascular
      surgery. How to go about diminishing anxiety?].

PMID- 9934090
TI  - [Developing creativity in nursing students. Nursing with soul].

PMID- 9934092
TI  - [Caring for surgical patients. Nutritional perioperative care].

PMID- 9934091
TI  - [Futuristic scenario. Manfred's awakening].

PMID- 9934093
TI  - [Ethics in everyday life. Avoiding the traps of power].

PMID- 9934094
TI  - The basics of neonatal EKG interpretation.
AB  - This article reviews the basic physiologic principles of the cardiac impulse and
      the EKG. It then relates these findings to the unique findings of the neonate and
      premature infant. Emphasis is placed on familiarizing nurses with the factors
      affecting the basic neonatal EKG and on the usefulness of cardiac rhythm strips
      and 12-lead EKGs. Topics addressed include evaluation of neonatal heart rate,
      examination of components of the cardiac cycle, identification of possible
      cardiac dysfunction, recognition of electrolyte imbalances, and effects of
      digoxin administration on cardiac rhythm.

PMID- 9934095
TI  - Understanding gastroschisis: an abdominal wall defect.
AB  - Gastroschisis is an abdominal wall defect found in the newborn that requires
      immediate interventions in the delivery room. To provide appropriate management,
      clinicians must have a clear understanding of the etiology and pathophysiology of
      gastroschisis. Stabilization in the delivery room is important and begins with
      establishing an airway, preventing hypothermia, and protecting the exposed bowel
      from the environment. Surgical treatment is required in the early neonatal
      period. Adequate preparation prior to repair is essential to ensure optimal
      outcomes.

PMID- 9934096
TI  - Thrombocytopenia in the newborn.
AB  - Thrombocytopenia in the newborn is a common finding in both preterm and term
      infants. It is associated with significant morbidity and mortality, the most
      serious cause of which is intraventricular hemorrhage. Thrombocytopenia can be
      attributed to many neonatal disorders that are common in the NICU. This article
      reviews the physiology of normal platelet production and hemostasis in the
      newborn. It discusses some of the disorders that cause thrombocytopenia. It also
      discusses the diagnosis and treatment of thrombocytopenia to give the nurse a
      better understanding of the disease process.

PMID- 9934097
TI  - Universal hearing screening: a community obligation.

PMID- 9934098
TI  - A clinical ladder for NNPs.

PMID- 9934099
TI  - Abdominal wall defects.

PMID- 9934101
TI  - Incorporating research in the classroom: a challenge for nursing faculty.

PMID- 9934100
TI  - Economics and nursing practice.

PMID- 9934102
TI  - The learning communities concept: increasing student involvement.

PMID- 9934103
TI  - Psychiatric nursing: has it been forgotten in contemporary nursing education?
AB  - Contemporary nursing education in Victoria, Australia aims to produce graduates
      with the capacity for employment in all areas of nursing at beginning
      practitioner level. Despite this aim, psychiatric nursing occupies a relatively
      small proportion of undergraduate curricula. Research findings suggest that
      psychiatric nursing does not emerge as a popular career choice within
      comprehensive education. To prevent a crisis in nursing education, greater
      attention must be devoted to the theory and practice of psychiatric nursing, so
      that it can occupy a position of equal importance to other areas of nursing
      practice.

PMID- 9934104
TI  - Allocation of resources: a student simulation.

PMID- 9934105
TI  - Benefits and challenges of a graduate nursing consortium.
AB  - The Intercollegiate Consortium for a Master of Science in Nursing (ICMSN), a
      partnership among four universities in Louisiana, is a proven articulation model
      for delivering graduate education in nursing. The authors describe the benefits
      and challenges of an academic consortium. Recommendations are offered for
      establishing similar models of multi-institutional collaboration in higher
      education.

PMID- 9934106
TI  - Documenting the scholarship of clinical teaching through peer review.
AB  - The essence of teaching is to make a positive difference in the lives of
      students. To this end, the nursing department at Kent State University developed
      and implemented a faculty-driven, voluntary program for peer review of clinical
      teaching. The authors describe the clinical peer review program and its positive
      outcomes.

PMID- 9934107
TI  - Nursing home residents as participants in an undergraduate physical assessment
      course.

PMID- 9934108
TI  - Using concept maps and visual representations for collaborative curriculum
      development.
AB  - A picture is worth a thousand words, and in the development of collaborative
      curricula among colleges and universities, a concept map or visual representation
      may save thousands of hours of semantic wrangling. Using pictures in curriculum
      development allows participants with varying backgrounds to share their visions
      and values, and promotes work at the conceptual level before detailed planning
      proceeds. A curriculum development team found the use of concept mapping and
      visual representations to be one of their most valuable means of developing
      consensus among three faculty groups and practicing nurses. The authors examine
      concept mapping as a heuristic tool for curriculum development in the context of
      creating a joint collaborative nursing curriculum in two languages among a
      university and two community colleges. The use of other visual representations to
      compensate for some of the limitations of concept mapping are also described.
      Recommendations are made based on the authors' experience with these tools.

PMID- 9934109
TI  - From authorship to contributorship. Promoting integrity in research publication.
AB  - Shared authorship in nursing research presents practical and ethical dilemmas and
      does not effectively capture individual research participation and
      accountability. This study, which defined author contributions and practices in
      multiauthored nursing research, contributed to a better understanding of
      contemporary author participation and the inherent challenges faced by nurse
      scholars in determining authorship credit. A method of "contributorship" is
      proposed which would delineate individual contributions to the research project
      while maintaining professional integrity, scientific accountability, and
      scholarly recognition.

PMID- 9934110
TI  - Implementing a rural nursing course.
AB  - Southern Alberta is essentially a rural Canadian province and therefore an ideal
      setting for offering a rural-focused nursing course. Considering the need for
      professional nurse preparation with a rural focus, three schools of nursing in
      the Province collaborated to launch their first rural nursing course. The authors
      elaborate on the process of developing the course, then establishing partnerships
      with rural communities to provide opportunities for a nursing practicum.

PMID- 9934111
TI  - Finding the right faculty. The important job of the search committee.
AB  - Nursing programs must face the challenge to recruit and retain qualified faculty
      who are committed to the institution and the profession. In these times of scarce
      financial resources, increased faculty retirements, and a declining faculty
      applicant pool, the search committee must make wise choices for searching and
      hiring replacement faculty. The authors discuss how the search committee can
      effectively conduct a search, review applications, interview, hire, and orient
      qualified faculty replacements.

PMID- 9934112
TI  - Creating clinical opportunities in a managed care environment.
AB  - The Continuum of Care clinical experience was developed to provide future nurses
      with practice in a managed care environment. Students see how the critical care
      patient's needs change during the recovery process and assist the patient with
      the transition to self-care at home. Patient and student evaluations indicate the
      experience increases students' understanding of the role of the nurse in managed
      care while facilitating patients' transition to the self-care environment.

PMID- 9934113
TI  - Recognizing the contributions of case management. An annual evaluation.

PMID- 9934114
TI  - Nurse case managers' opinions of their role.
AB  - Delphi and focus group methods were used to identify nurse case managers' (NCMs')
      opinions regarding their professional role. This study convened 15 NCMs from a
      regional medical center in the southeastern United States. Findings present the
      highest-rated items influencing the NCM role, as well as a definition and model
      depicting the role's essential elements. In study questionnaires, participants
      were asked to identify and subsequently rate items in seven categories. The
      overall highest-rated item was the personal attribute of critical thinking and
      prioritizing. The second highest-rated response was the critical function of
      coordinating a multidisciplinary plan of care. Interdisciplinary support and
      participative decision making were consistently ranked as important
      organizational factors. In the category of impact on health care outcomes,
      identifying patient needs and services was highly rated. Participants suggested
      that NCM assignments should be based on clinical knowledge and expertise, with a
      focus on prevention. Practice implications, based on the findings, are
      emphasized.

PMID- 9934115
TI  - Surfing the Internet.

PMID- 9934116
TI  - Computerized documentation of case management. From diagnosis to outcomes.
AB  - Documentation of patient care, outcomes, and report writing are important aspects
      of the role of the case manager. In this article, the author examines the types
      of documentation approaches used by nurses in recent years and the new
      applications called for in the case manager role. Issues such as standardized
      language and multidisciplinary documentation are explored. Approaches to
      examining computerized documentation systems are presented. Finally, the
      importance of documentation in demonstrating what nurses do, allowing comparison
      of outcomes, and supporting reimbursement for nurses, are discussed.

PMID- 9934117
TI  - Implementation of an interdisciplinary clinical pathway for patients after a
      liver transplant.

PMID- 9934118
TI  - Overtime reduction with the press of a button. An unexpected outcome of
      computerized documentation.
AB  - Overtime takes its toll on the staff and creates an opportunity to control cost.
      The purpose of this research was to investigate actual and perceived overtime
      amounts of nursing staff members before and after the implementation of a
      handheld computerized patient documentation system. Overtime amounts have
      decreased 29% since implementation of the system. Advantages and disadvantages of
      the system are also discussed.

PMID- 9934119
TI  - Piloting your case management career.

PMID- 9934120
TI  - Policy implications when changing staff mix.

PMID- 9934121
TI  - The alternative health care revolution.

PMID- 9934122
TI  - Nurse leaders as advocates in community hospital conversions.

PMID- 9934123
TI  - A cost analysis of a nursing center's services.

PMID- 9934124
TI  - The 'me' disease.

PMID- 9934125
TI  - Legislative and regulatory activities in the 105th Congress.

PMID- 9934126
TI  - An innovative approach to appropriate resource utilization.

PMID- 9934127
TI  - Integrated care management: aligning medical call centers and nurse triage
      services.
AB  - Successful integrated delivery systems must aggressively design new approaches to
      managing patient care. Implementing a comprehensive care management model to
      coordinate patient care across the continuum is essential to improving patient
      care and reducing costs. The practice of telephone nursing and the need for
      experienced registered nurses to staff medical call centers, nurse triage
      centers, and outbound telemanagement is expanding as the penetration of full-risk
      capitated managed care contracts are signed. As health systems design their new
      care delivery approaches and care management models, medical call centers will be
      an integral approach to managing demand for services, chronic illnesses, and
      prevention strategies.

PMID- 9934128
TI  - Bonuses, career moves, & job support.

PMID- 9934129
TI  - It's time to adopt Internet technology.

PMID- 9934130
TI  - Entrepreneurship: is it for you?

PMID- 9934131
TI  - Epilepsy: a journey.
AB  - Epilepsy is a tendency to have recurrent fits or seizures, and for most people is
      an uncomfortable and socially unacceptable thing to witness. It is estimated that
      420,000 people in the UK will develop the condition in one form or another, with
      the risk of death three times higher than in the general population. There are
      over forty different types of seizure; each type presents itself differently from
      one person to another. However, the cause of the epilepsy is always the same; it
      is due to abnormal electrical activity within the brain (Fenwick and Fenwick
      1996). The aim of this Learning Unit is to improve the understanding of epilepsy
      among nurses.

PMID- 9934132
TI  - Gender matters.
AB  - The concept of gender is about more than just sex. Gender is made up of a system
      of meanings related to power and status. It operates at individual, interactional
      and cultural levels to structure people's lives (Unger and Crawford 1996). The
      aim of this learning unit is to explore issues concerned with gender and women's
      health. The unit discusses different approaches and strategies that nurses,
      midwives and health visitors can use to offer women progressive gender-aware
      health care.

PMID- 9934133
TI  - Stamp Out Violence campaign.

PMID- 9934134
TI  - Striking the right note.

PMID- 9934135
TI  - Grief encounters.

PMID- 9934136
TI  - Milk monitors.

PMID- 9934137
TI  - There but for the grace of God.

PMID- 9934139
TI  - It is time for nurses to acknowledge their place in Europe.

PMID- 9934138
TI  - Someone tell the media that nurses can do more than make beds.

PMID- 9934140
TI  - The code of conduct was supposed to offer universal standards in nursing.

PMID- 9934141
TI  - In terminal decline.

PMID- 9934142
TI  - A bitter pill.

PMID- 9934143
TI  - The highway code.

PMID- 9934144
TI  - Violent times.

PMID- 9934145
TI  - Unnatural selection.

PMID- 9934146
TI  - Cutting edge care.

PMID- 9934147
TI  - Injection technique. Depot drugs.

PMID- 9934148
TI  - Stroke of genius.

PMID- 9934149
TI  - Fragile X syndrome.

PMID- 9934150
TI  - School run. Interview by Craig Kenny.

PMID- 9934151
TI  - Clearing tracheobronchial secretions using suction.

PMID- 9934152
TI  - Support role.

PMID- 9934153
TI  - Trichomonas vaginalis: signs, tests and treatment.

PMID- 9934154
TI  - Turning evidence into everyday practice.
AB  - This article focuses on ways in which implementation projects can ensure that
      work on clinical quality becomes normal business in NHS organisations. It draws
      on the work in the 16 PACE projects and other discussions to suggest a model for
      moving from project to mainstream work. It concludes by suggesting some
      implications of this way of working for future arrangements for clinical
      governance.

PMID- 9934155
TI  - Clinically effective leg ulcer care.
AB  - Leg ulcers are a common and debilitating problem. Despite the presence of
      evidence to suggest that certain treatments can provide effective management,
      there are widespread variations in the provision of care. The project examined
      here brought together staff from both acute hospital and community settings. As a
      result the availability of education, training and materials to ensure evidence
      based practice was improved.

PMID- 9934156
TI  - Continence: a case for home delivery services.

PMID- 9934157
TI  - Dirty business.
AB  - About 5% of adults and 8-10% of children in the UK have asthma. Much media
      attention has been given to the effects on health of air pollution and it is a
      matter of common conjecture that the rising levels of traffic and resultant
      emissions are directly responsible for the simultaneous rise in the incidence of
      asthma. Undoubtedly there has been a significant rise in the number of admissions
      to hospital for asthma episodes in the UK over the past decade and this is
      demonstrably synchronous with a rise in the atmospheric levels of air pollution
      (Department of Health, 1995). This article questions whether there is research
      evidence that air pollution is responsible for this rise, and whether any such
      evidence can be used by nurses advising patients.

PMID- 9934158
TI  - A vexing vaccination.

PMID- 9934159
TI  - Stamp out violence.

PMID- 9934160
TI  - Bills of health.

PMID- 9934161
TI  - Bruised but not beaten. Interview by Adrian O'Dowd.

PMID- 9934162
TI  - Friday night frighteners.

PMID- 9934163
TI  - A matter of birth and death.

PMID- 9934164
TI  - Nursing agencies are not the bad guys.

PMID- 9934165
TI  - Choose life.

PMID- 9934166
TI  - Early lifesavers.

PMID- 9934167
TI  - Express yourselves.

PMID- 9934168
TI  - Orthodox care.

PMID- 9934169
TI  - No thanks for the memories.

PMID- 9934170
TI  - Past comes to the present. Interview by John Bennett.

PMID- 9934171
TI  - NT/3M National Nursing Awards. Unit trust.

PMID- 9934173
TI  - Pay and display.

PMID- 9934172
TI  - Face to face. Interview by Eileen Fursland.

PMID- 9934174
TI  - Collecting a sputum specimen.

PMID- 9934175
TI  - Working well.

PMID- 9934177
TI  - Palliative care for people with non-malignant diseases.

PMID- 9934176
TI  - Caring for patients with an ICD.
AB  - The internal cardioverter defibrillator corrects life-threatening arrhythmias by
      providing antitachycardia pacing, pacing for bradycardia, and cardioversion or
      defibrillation shocks. However, there is little warning that the device may fire,
      which can cause physical, social and psychological problems for the patient.
      Nurses caring for ICD patients in the community and in hospital need to know what
      it is like to live with this device, how it works and the implications for other
      treatments.

PMID- 9934178
TI  - Education for specialist practice in palliative care.

PMID- 9934179
TI  - Value-added benefits.

PMID- 9934180
TI  - Beating the odds in liver disease.

PMID- 9934182
TI  - [Health and nursing legislation--a short backward glance and some perspectives]
      [In Process Citation]

PMID- 9934181
TI  - Nutrition and stoma patients.

PMID- 9934183
TI  - [Qualifications for supervisory nursing according to the health care and nursing
      law].

PMID- 9934184
TI  - [Juridical foundations: practical education in health care and nursing].

PMID- 9934185
TI  - [Legislation on health care and nursing ... our constant companion].

PMID- 9934187
TI  - [Aspects of learning theory].

PMID- 9934186
TI  - [Ritual and theory--two incompatible opposites?].

PMID- 9934188
TI  - [The need for information in female patients with malignant diseases in the head
      and neck region. Between need and reality].

PMID- 9934189
TI  - ["A trip into the unknown...." The Feldkirch nursing society].

PMID- 9934190
TI  - Do outcomes equal quality?

PMID- 9934191
TI  - Contextual variables and assessment of the outcome effects of nursing
      interventions.

PMID- 9934192
TI  - Role of outcomes management in marketing to managed care companies: why use
      outcomes data?

PMID- 9934193
TI  - Methodological issues in treatment effectiveness and outcomes research.
AB  - The authors define treatment effectiveness and outcomes research, then discuss
      three critical methodological issues that if not appropriately resolved, can
      invalidate the findings of such studies. The three issues are research design,
      comparability of treatment groups, and approaches to measurement. These issues
      must be considered when the quality and contribution of findings from treatment
      effectiveness and outcomes research are evaluated.

PMID- 9934194
TI  - Psychometric analysis of the problem rating scale for outcomes.
AB  - The current emphasis on outcomes management and outcomes research projects is
      stimulating interest in the psychometric properties of computerized clinical data
      bases among nurses and other health care providers. The knowledge, behavior, and
      status subscales of the Omaha System's Problem Rating Scale for Outcomes (PRSO)
      were evaluated for interrater reliability and content validity. The authors
      describe the methods used and the results of that research.

PMID- 9934195
TI  - Rural versus urban home health: does locale influence OASIS outcomes?
AB  - As home health administrators select performance evaluation systems to meet the
      benchmark requirements of the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO), a frequently asked question is: Does rural versus urban
      locale influence patient outcomes? To answer the question, patient outcome data
      were collected from rural and urban home health agencies. Data analysis showed
      better outcomes for rural than for urban patients. Locale predicted less than 1%
      percent of the variance in each of the five outcomes studied. Factors that could
      account for rural-urban outcome differences were suggested.

PMID- 9934196
TI  - Comparison between reports of care obtained by postdischarge telephone interview
      and predischarge personal interview.
AB  - The question of when to survey patients is the subject of ongoing debate because
      of the rising interest in monitoring quality from the consumer's perspective.
      This study of 772 randomly assigned patients from 17 hospitals compared results
      from predischarge in-person interviews (HI) and postdischarge telephone
      interviews (PHTI) for differences in participation rates, respondents'
      characteristics, and reports of quality most affected by nursing. The methods
      were equally costly. The results suggest that hospital interviews may enhance
      response rates of some vulnerable patient groups without jeopardizing the
      results.

PMID- 9934197
TI  - Panning for gold: sifting through chart audit data for patient outcomes.
AB  - Randomly observing patients after a 6-month period of clinic visits that included
      time for an educational component revealed that although patients were making
      positive changes to improve their health, an identifiable pattern of improvement
      in health status was not apparent. A chart audit was performed to gather
      demographic and outcome data in a more systematic manner. This article describes
      the process for completing the chart audit and analyzing the data. The potential
      for chart audits to raise research questions for subsequent development of
      outcomes evaluation studies is discussed. The author presents a model for a
      health care outcome research study that can be applied to improve effectiveness
      of care.

PMID- 9934198
TI  - Estimating the cognitive ability of nursing home residents from the minimum data
      set.
AB  - Two methods have been developed for using the Minimum Data Set (MDS) to estimate
      cognitive ability, the Cognitive Performance Scale (CPS) and the MDS Cognition
      Scale (MSD-COGS). The relative utility of the two scales was compared by
      correlating them with the Mini-Mental State Exam the Global Deterioration Scale
      in a sample of 290 nursing home residents with a mean age of 87 years. Both the
      CPS and the MDS-COGS related quite strongly to the Mini-Mental State Exam and to
      the Global Deterioration Scale, with the MDS-COGS correlating at slightly higher
      levels than the CPS. The CPS and the MDS-COGS both provide a simple,
      straightforward method of assessing cognitive function that is easy to understand
      and clinically meaningful. Because both are derived from the MDS, administration
      costs, as compared with that of the Mini-Mental State Exam or the Global
      Deterioration Scale, are also substantially lower. Inasmuch as the data are
      already available and the procedure is so simple (particularly with the MDS
      COGS), it might be of benefit to include a computation of cognitive function as
      part of the MDS profile.

PMID- 9934199
TI  - [After the elections].

PMID- 9934200
TI  - [Continuing education: care of the oncologic chronically ill patient].

PMID- 9934201
TI  - [The process of truth disclosure: a crisis situation for the patient and a
      challenge for the nursing team].

PMID- 9934202
TI  - [High-dose chemotherapy in a day clinic].

PMID- 9934203
TI  - [Model experiment in joint nursing education].

PMID- 9934204
TI  - [Emergency assistance in Srebrenica--solidarity instead of nursing].

PMID- 9934205
TI  - [The mine war against the children].

PMID- 9934206
TI  - [European conference on education in telecommunication and informatics in health
      care (HTE 98)].

PMID- 9934207
TI  - [5 decades of debate on structure. Ruth Elster, honorary chairman of the German
      Nursing Society on the crisis situation of the society].

PMID- 9934208
TI  - [The debate on the structure of the German Nursing Society].

PMID- 9934209
TI  - [The smiles were missing].

PMID- 9934210
TI  - [The Bamberg discussion on the theme of "Urinary Tract Infection and
      Incontinence". The patient's protection is borne by many shoulders].

PMID- 9934211
TI  - [Second HEWI forum in Bad Arolsen: barrier-free life begins in the head].

PMID- 9934212
TI  - [50 years Pflegezeitschrift: dialogue among nurses].

PMID- 9934213
TI  - [The German Federation of Nursing Professions is expecting a historical change:
      The federation is expected to relinquish its federal structure].

PMID- 9934214
TI  - [Schleswig-Holstein wants to work more effectively. An advisory board is
      replacing the county nursing conference].

PMID- 9934215
TI  - [The interdisciplinary Pediatric Intensive Care Unit at the Olga Hospital:
      parents too need care].

PMID- 9934216
TI  - [The Dortmund social court contradicts the health insurance companies. Patients
      have a right to a wheelchairs also in nursing homes].

PMID- 9934217
TI  - [Ten days as a patient in a gynecology unit. 1. Experiences that make you think].

PMID- 9934218
TI  - [Bringing together various hospital activities: Mrs. M.'s operation has to be
      postponed because...].

PMID- 9934219
TI  - [Physical effects of cancer and their treatment: making piece with the damaged
      body image].

PMID- 9934220
TI  - [Care of paraplegics. 3. Independence strengthens self reliance and self esteem].

PMID- 9934221
TI  - [Things to know about epilepsy: does the seizure come like lightning out of a
      clear sky?].

PMID- 9934222
TI  - [Touching is caring: respiration-stimulating massage promotes wellbeing].

PMID- 9934223
TI  - [Nursing standards in dermatoses. 2. A cure is not always possible. Nursing
      Standards in Dermatology work group].

PMID- 9934224
TI  - [Model hospitals in Berlin--the urban hospital: the center for activating care is
      the nucleus of the model].

PMID- 9934225
TI  - [Use of technology in the hospital: One can do without but it is of tremendous
      help].

PMID- 9934226
TI  - [Dealing with catastrophies in the hospital: emergency planning is often
      neglected].

PMID- 9934227
TI  - [Living with the farewell: reticence often leads to speechlessness and
      withdrawal].

PMID- 9934228
TI  - [Health and nursing legislation in Austria: nursing science and nursing research
      are legislated].

PMID- 9934229
TI  - [Nursing--the concept and its meaning in theory and research: definitions and
      comparison].

PMID- 9934230
TI  - [Rehabilitation of diabetic patients, amputated because of vascular disease.
      Angiology and vascular surgery services, 1995].
AB  - A descriptive and retrospective study of 95 patients from the "Ambrosio Grillo"
      and "Saturnino Lora" Hospitals, in Santiago de Cuba, was conducted between
      January and December, 1995, aimed at showing the rehabilitation of the diabetic
      patients, who have had a limb amputated due to vascular disease. These patients
      are a sample of the universe of lower limb amputees as a results of vascular
      disease. Diabetes mellitus increased the affection of the distal arterial arbor,
      which explains its high incidence among amputeez. The amputation of a lower limb
      is very significant for a patient, and it is considered as the final stage of the
      treatment since the patient's life is in danger due to a severe generalized
      sepsis of the extremity. General data from the medical histories, variables of
      interest as clinical data, risk factors, socioeconomic data, occupational
      category, and foot care were taken into consideration. Most of the patients were
      60-70. Females prevailed and the time of evolution of diabetes mellitus was over
      10 years. The rehabilitation activities include the psychical, physical and
      social aspects, and are carried out by a specialized working group.

PMID- 9934231
TI  - [The nurse's work in the application of ozone therapy in retinitis pigmentosa.
      January-May 1996].
AB  - A descriptive and prospective study of 73 patients suffering from retinitis
      pigmentosa, who were attended at the Provincial Center of Retinitis Pigmentosa,
      in Santiago de Cuba, from January to May, 1996, was conducted aimed at
      emphasizing the nurse's role in the application of ozonotherapy. There are
      different ways to administer this gast: autohemotherapy, intramuscular, artrectal
      insufflation. The information obtained was manually processed and percentage was
      used as a summary measure. The predominance of young and male patients is among
      the main results. Most of the patients were in stage II and III of the disease,
      and the rectal administration of ozone was the most used. This last aspect shows
      the significance of the nurse-patient relationship, which contributed decisively
      to the acceptance of rectal administration that was rejected by a great number of
      patients.

PMID- 9934232
TI  - [Neurosurgical patients in intermediate care. Annual study 1995].
AB  - The critical neurosurgical patient requires specialized nursing care. His
      satisfactory recovery depend an our nurses's work, since their permanence beside
      the patient and an appropriate treatment make them indispensable. A descriptive
      and retrospective study of 68 neurosurgical patients admitted at the Intermediate
      Therapy Unit of the "Gustavo Alderguia" Clinical ans Surgical Teaching Hospital
      was conducted to determine within the Nursing Care Process (NCP) the main
      specific nursing procedures and those variables of interest, such as sex, age,
      type of operation, NCP, mechanical ventilation, medication, evolution, and the
      nursing procedures carried out. A computerized system was used to analyze the
      data and the chi-square test of statistical significance. Of the 68 patients
      studied, 33 were males (p < 0.001). Patients aged 26-30 were the most affected.
      13 patients were operated on, and NCP was performed in 20% of the cases. The most
      important nursing care activities were the vital signs checking, the measurement
      of diuresis, and the active surveillance of neurological focalization and
      phlebitis (p < 0.001).

PMID- 9934233
TI  - [Results of preoperative preparation with mannitol in colorectal surgery. January
      December 1995].
AB  - A study on the results obtained in 20 patients selected by the simple randomized
      method, who were preoperatively prepared for colorectal surgery with the oral
      administration of manitol and complementary antimicrobial therapeutics at the
      ASaturnino Lora@ Provincial Teaching Hospital, in Santiago de Cuba, from January
      to December, 1995, was conducted aimed at evaluating the results attained with
      the use of manitol in the preoperative preparation for colorectal surgery,
      determining its complications, analyzing its advantages, and assessing the
      patient, nurse and surgeon's opinion about the new procedure. The following
      variables were taken into account: age, preoperative diagnosis and previous
      operations. The percentage statistical method was used. Most of the patients were
      elderly, who were able to undergo surgery. There were no complications in
      connection with the preoperative preparation, which has the following advantages:
      it is simpler and more efficient that the traditional use of enemas, it is easy
      to apply, it saves time and resources on reducing the preoperative stay, it is
      considered as more comfortable for patients and nurses, and it is much more
      economic and effective, which was proved by surgeons during the operation.

PMID- 9934234
TI  - [Computerized simulations in nursing education. Faculty of Medical Sciences of
      Pinar del Rio, 1982-1995].
AB  - This study is based on a pedagogical experience obtained with the use of
      computerized simulations in the baccalaureate degree program. It consists in
      preparing under certain technical norms a situation reflecting a real event the
      student will face in the future. It is aimed at showing the level of
      effectiveness attained by automated simulations in Nursing education, comparing
      it with the traditional methods (seminars). Two groups were organized to this
      end: a case base study with simulations, and a control group with the traditional
      method. 38 4th-year nursing students who were passing through the Community
      Health Nursing rotation took part in this study. On analyzing the results by
      frequent evaluations and final tests, it was proved that it is easier for
      students to get 5 at traditional seminars, which may be caused by the
      rigorousness of simulations, since they measure all the students' decisions
      individually. Students using simulations obtained better qualitative results in
      the final evaluation. The time used for the development of simulations was no
      langer than 15 minutes. Students consider the method as useful, since it allows
      them, to get closer to computers, to prepare for the future and to develop
      creativity. It is concluded that simulations should be used as an evaluation
      system.

PMID- 9934236
TI  - [Systematization of the experiences of 2 years of work. Arimao Population
      Council].
AB  - The community and social participation as an action has been part of the daily
      life every group and community. A descriptive and qualitative study of the 2-year
      period 1994-1996 was conducted to determine the hygienic, sanitary,
      socioeconomic, sports, cultural and health transformation occurred at the
      circumscription # 73 of the ABalcon Arimao@ People's Council, in La Lisa
      municipality, which is located in an insalubrious suburb with a high criminal
      rate, school dropout and unemployment, that is subjected to social actions. The
      method of Experience Systematization of Oscar Hara in 5 times was applied and
      included in the living process of this community in addition to life histories.
      The most important achievement was to gather all the social members of the
      community, with their mobilization capacity, under the leadership of the main
      conductors of the process through an innovative methodology starting from its
      context. Positive changes were observed in the life style and the health status
      of the population.

PMID- 9934235
TI  - [Identification of suicide indicators in general patients by the primary care
      nurse].
AB  - An informative descriptive study is conducted aimed at making nurses know about
      some essential aspects of suicide (characteristics, risk, indicators, methods for
      diagnosis and intervention) in order to increase the effectiveness of their role
      in the prevention of this health problem, having determined previously the
      information needs of these professionals. It is analyzed how useful it is the
      utilization of the nursing care process to approach those patients and families
      with suicide risk. The main signs of danger for suicidal behavior, as well as the
      essential risk factors and the most important methods to detect both indicators
      early are explained. Nurses are also instructed what to do with a patient with
      suicidal indicators and his family. It is concluded that a better training of
      these professionals will contribute to reduce the suicide impact on the
      community.

PMID- 9934238
TI  - [Evaluation of the introductory course for nursing licensure. Faculty of Medical
      Sciences, February-June 1996].
AB  - A cross sectional study of 20 nursing baccalaureates, 14 heads of department, 4
      methodologists and 2 professors from the faculties of medical sciences of the
      country was conducted with the objective of assessing the efficiency of the
      introductory course for future nursing baccalaureates, and of suggesting new
      topics for its development. A formulary was applied by using the survey method.
      Primary data were taken and processed by a traditional statistical method. It was
      proved that 95% of the sample considered this course as important, whereas 85%
      expressed that students were little motivated, and 35% recommended to make it
      langer.

PMID- 9934237
TI  - [The nurses' role in the control of diabetic patients].
AB  - At present diabetes mellitus is a health problem that increases as the society
      develops. A retrospective and descriptive investigation was made with 21 diabetic
      patients from the health area of the "Josue Pais Garcia" Polyclinic, in Santiago
      de Cuba, from January to December, 1994. The survey used included the following
      variables: age, sex, occupation, attendance to the Diabetic Care Center,
      distribution according to the type of diabetes, knowledge of this disease,
      participation in physical exercises and fulfillment of the therapeutic. There was
      a predominance of female patients over 46 and of non-insulin dependent or type II
      patients. The completion of the essential aspects in the treatment of these
      patients was proved in 76.1% of the sample.

PMID- 9934239
TI  - [Qualitative study on integrated care for children and adolescents].
AB  - This paper presents the theoretical reference and methodology applied by the
      Group of Study on Children's and Adolescent's Health of the University of Sao
      Paulo at Ribeirao Preto College of Nursing, in their qualitative research aiming
      at the integral assistance to children's and adolescent's health. The authors
      describe the health sector in current Brazilian society, where the health actions
      take place, following with the presentation of the Study Group. After that, they
      develop the theoretical reference and methodology, defining the analytical-
      politics and social policies, technological organization of work, health
      services, child and family. To conclude, the authors present an outline of the
      results of investigations carried out in the last three years (1995 to 1997).

PMID- 9934240
TI  - [Sources of meaning of caring and lack of caring in a pediatric hospital].
AB  - Exploratory study, that is part of a set of data collected through interviews
      with 10 clients admitted to a pediatric hospital, with the purpose to identify
      meanings and sources of caring and non caring. Caring encompasses three meanings:
      professional caring, parental caring and friendly caring. Non caring means the
      lack of interest of health professionals who perform procedures without attention
      and respect for the human being. Caring actions and behaviors are mentioned more
      frequently than those of non caring. Results also revealed that parents, health
      professionals, hospital personnel, visitors and roommates make clients feel cared
      for.

PMID- 9934241
TI  - [Prescription for the day: infusion of cheer. Using art as an instrument in the
      care of hospitalized children].
AB  - The purpose of this study is to report on the experiment of a group of
      undergraduate students from the University of Sao Paulo at Ribeirao Preto College
      of Nursing, who use art (some aspects of the Clown Theatre) as a nursing resource
      in the care to hospitalized children. Having as basis the job performed by the
      group of physicians "Joy Doctors", and the theoretical grounding from Psychology
      and Pediatric and Neonatal Nursing, those students founded the Laugh Company that
      aims at rescuing laugh within the hospitalized child/family. This experiment has
      caused some changes in daily care: the hospital space has become more informal
      and relaxed, laugh can be heard more often and some items, such as, objects,
      sounds, movements, colours, rooms and people can become toys.

PMID- 9934242
TI  - [The meaning of school failure to social activists who use the program of primary
      care school health--PROASE at the municipality of Ribeirao Preto].
AB  - The present study has the purpose to identify and analyze the meaning of school
      failure to social actors that use or work in the Program of School Health Primary
      Care--PROASE (family members, health and education professionals) and to
      articulate their discourse with the official discourse in order to establish the
      program's future actions. Our study has a qualitative theoretical framework based
      in Minayo (1992). One area where PROASE develops its activities was chosen and by
      semistructured interviews and documentation analysis it was possible to know how
      the three segments that compose the sample understand the meaning of school
      failure.

PMID- 9934243
TI  - [Meaning of the health concept from the perspective of families at personal and
      social risk].
AB  - The purpose of this study is to describe the meaning of health through the
      perspective of families under personal and social risk situations. The
      ethnographic analysis based the investigation and data were collected through
      interviews with the low income families of children attended by a Communitary
      Center in Sao Paulo city. The analysis of the interview contents allowed the
      identification of 7 cultural domains. The results of this study show the
      characteristics of knowledge, values and behaviours about the health concept,
      that are relevant to families, enabling the understanding of the family
      organization, that is significant to health care of each member and also the
      central role carried out by mothers in the studied culture.

PMID- 9934244
TI  - [Women's labor force in Chile: figures and characteristics].
AB  - The present article shows us some sociodemographic characteristics of the women
      labour force in Chile, and the difficulties they have to accede and to maintain
      their labour source due to gender conditions.

PMID- 9934246
TI  - [Leadership in nursing in Brazil: approaching its demystification].
AB  - This study aims at understanding the view about the nursing leadership question,
      through critical analysis of the literature produced predominantly in Brazil on
      this theme, from 1930 to 1995, contributing to its "dismythification". From the
      assumption that nursing is a social practice, and therefore articulated with
      other health practices, we conducted the investigation under a historical-social
      approach. Empirical data were obtained from the discourses about the issue or
      related themes, contained in 14 periodicals, from which 12 were of nursing.
      Besides them, we used proceedings from nursing events, as well as research and
      researcher catalogs and 3 theses. We analysed data according to time
      delimitation, distributed in four historical periods, intending to maintain the
      similarity of the peculiar discourses of each period, according to the context in
      these moments. The study demonstrated that the nursing leadership question has
      been treated, in the profession, in an idealized, mythical and crystalized way,
      contributing, thus, to the maintenance of the status quo and nursing
      professional's alienation.

PMID- 9934245
TI  - [Women and AIDS: profile of an infected population and its social implications].
AB  - This study aimed to identify the profile of women with AIDS from a Health Service
      located in Sao Paulo City, from October to December, 1995. The data obtained from
      medical charts allowed to characterize the profile in terms of age, school
      degree, marital status, occupation, exposed category and mean survival time.
      Besides, it was possible to know the number of children--sons and daughters of
      those women--that might be real or potential AIDS' orphans, an important social
      problem involving the phenomena. Authors discuss the women's particularities in
      the process of the disease and the social implications related to the spread of
      the infection in this group.

PMID- 9934247
TI  - [Leadership and communication in nursing management].
AB  - Considering communication and leadership, authors examine the role of the leader
      as a focus of reception and transmission of information, based on the
      classification of Mintzberg related to their informative roles, such as the
      leader acting as monitor, disseminator and spokesman. Contextualizing this
      approach in the scenery of nursing management, authors study the dimension of
      nurses-leaders role as an essential element of communication in the systems of
      organization of nursing care.

PMID- 9934248
TI  - [Establishment of an ambulatory surgery service; the nurses' role in this
      scenario].
AB  - The purpose of the present study is to present the trajectory of a nurse in
      establishing a service of ambulatory surgeries in a general hospital. It
      approaches the importance of such a service in the contemporary context,
      considering the activities developed by the nurse and nursing staff, as well as
      the challenges and conquests found in daily work.

PMID- 9934249
TI  - [Psychiatric nursing research: concepts and expectations of nurses in psychiatric
      institutions].
AB  - This research has as objects of study the conceptions and expectations of the
      clinical nurses in psychiatric institutions about the research developed in this
      area. It has the purpose to identify conceptions and expectations, enabling the
      identification of the process of dissemination and utilization of the research in
      the attention and administration of psychiatric nursing care. It was developed
      with nurses that work in psychiatric institutions at Salvador, in March, 1997. 25
      nurses who worked in the period were interviewed expressing their opinions
      concerning the theme in study, through semi-structured interview. Results were
      quantitatively analysed, based on the theoretical-methodological design of the
      Social Representations. It was possible to conclude that the great part of the
      nurses interviewed mentioned that they did not have access to research in this
      area, as well as demonstrated difficulty of find the relations and influence of
      these research in their service, however they admit its importance to personal
      and professional development, that certainly, reflects on nursing care.

PMID- 9934251
TI  - [The student's page. Learning about the growth and development of children:
      report of experiences].

PMID- 9934250
TI  - [Nursing profession in epidemiologic surveillance at Ribeirao Preto (1988-1996)].
AB  - The insertion of the nursing profession in Epidemiologic Surveillance (ES) at
      Ribeirao Preto from 1988 to 1996 has been identified in the process of health
      care decentralization. The qualitative methodology is used based in bibliographic
      and documentation sources and by 8 semi-structured interviews. Nurses are in
      greater number than all other health professionals and their practice are based
      on the Epidemiology and management of control side, represented by notifications
      and visits, and the prevention side, represented by immunization.

PMID- 9934252
TI  - [The student's page. The nursing student caring for a child with chronic pain:
      report of experiences].

PMID- 9934253
TI  - [Tutoring, apprenticeship and the relationship between theory and practice: the
      open knots].

PMID- 9934254
TI  - [Forms and methods of tutorship in the university nursing diploma. Consensus
      conference in San Miniato, November 1997)].
AB  - The contribution presented is the result of a workshop with the participation of
      nurses, educationalists and course directors involved in the education of student
      nurses. The different educational experiences and organizational styles adopted
      in nursing schools were compared and some reflections on the role and expected
      competences of the nurse tutor, responsible of the theoretical and practical
      training of student nurses are formulated. The consensus document analyzes the
      implications related to the different definitions of the role of the nurse-tutor
      and each different role is discussed according to the theoretical model it
      derives from. Different educational strategies are discussed and eventually
      proposals on the education and educational requirements of the nurse-tutor are
      made.

PMID- 9934255
TI  - [Processes and strategies of teaching from the experiences the tutor elicits in
      the apprentice].
AB  - The teaching styles adopted by the 10 nurse-tutors of the Trento Nursing School,
      that teach students during their practical training to elicit the experiential
      learning, were studied. The instruments adopted were a questionnaire and five
      vignettes. The nurses were asked to 'think aloud' (verbal protocol technique) and
      practically explain how they would have used the case presented if occurred
      during the practical training of one of their students. The most widely adopted
      style is the connection between theory and practice, while less efforts are made
      to support the student from the emotional point of view and to help her/him to
      reflect on the feelings experienced during practice. The teaching style is
      supportive (5 nurse-tutors) and directive (the other 5 tutors). The small sample
      size does not allow reasonable comparisons between novice and expert tutors. The
      tutor's experience in the specific ward where students have their practical
      training leads to the adoption of a more supportive style, to a minor use of
      judgements and to a deeper exploration of the students' reasoning.

PMID- 9934256
TI  - [Factors influencing the learning process during apprenticeship. Study of the
      nursing students' perceptions in the Trento Nursing School].
AB  - The characteristics of teaching wards perceived by third year students of Trento
      nursing school as favouring the clinical teaching and learning were studied. The
      aim of the study was to identify the characteristics that favour or hamper the
      learning processes in order to identify the criteria for selecting the teaching
      wards. An open ended questionnaire was administered to the 60 third year students
      in may 1996. The most important variables favouring the learning processes were
      the opportunity to work with a registered nurse and the willingness of the
      medical and nursing personnel to teach in the word. Sixty-six percent of the
      respondents consider as pivotal to have a reference person or guidance (head
      nurses, clinical supervisors, expert nurses); 71.6% of the students find very
      valuable the variety of clinical cases and technique performed in the wards.
      Eighty-eight per cent of the students perceive that a good interpersonal
      relationship between the team and the students is a very important factor while a
      negative "social climate" has a negative impact on learning. Thirty-six per cent
      of the students state that a very high workload in the ward does not allow the
      student to pursue the aims of the educational project.

PMID- 9934257
TI  - [Prevention of the major complications of diabetes mellitus. What is the
      evidence?].

PMID- 9934258
TI  - [International observations. Nursing education in Finland. A visit at the Oulu
      Polytechnic].

PMID- 9934259
TI  - [The trade of women: from slavery to prostitution. Coordinamento Nazionale delle
      Comunita di Accoglienza].

PMID- 9934260
TI  - [Medical strategy. Neurogenic urinary incontinence].

PMID- 9934261
TI  - [A nurse's point of view. Recognizing the place of rehabilitation nurses].

PMID- 9934262
TI  - [Urinary incontinence. Nursing management. Adapting the protocols].

PMID- 9934263
TI  - [Urinary incontinence. Nursing management. Hygiene and comfort].

PMID- 9934264
TI  - [Medical strategy. Urinary incontinence in women].

PMID- 9934265
TI  - ["Regaining continence..."].

PMID- 9934266
TI  - [Urinary incontinence. Nursing management. Care at home].

PMID- 9934267
TI  - [Urinary incontinence. Nursing management. Intermittent non-sterile self
      catheterization].

PMID- 9934268
TI  - [Incontinence is no longer considered an inevitable fate].

PMID- 9934269
TI  - [Opening the shutters ... to open the eyes].

PMID- 9934270
TI  - [Public health. The health of children in school].

PMID- 9934271
TI  - [The hospital-centered view of home hospitalization must be developed. Interview
      by Marie Hetier].

PMID- 9934272
TI  - [Denouncing hypocrisy].

PMID- 9934273
TI  - [Quality/accreditation. The yearly evaluation discussion].

PMID- 9934274
TI  - [Professional practice. The nursing code].

PMID- 9934275
TI  - [Epidemiology of infectious diseases in France].

PMID- 9934276
TI  - [Development of a drug].

PMID- 9934277
TI  - [Patients' rights. 2. Treatment of pain].

PMID- 9934278
TI  - [Emergencies. How to treat a burn patient].

PMID- 9934279
TI  - [Diagnosis--intervention. Getting dressed].

PMID- 9934280
TI  - A bitter lesson.

PMID- 9934282
TI  - What the leechmaster taught me.

PMID- 9934281
TI  - Realistic faculty workforce assessments.

PMID- 9934283
TI  - International partnerships for health care reform.

PMID- 9934284
TI  - An old dog learns a new trick.

PMID- 9934285
TI  - We create and can remove the roadblocks to good basic science education.

PMID- 9934286
TI  - Capping off the medical curriculum: our approach.

PMID- 9934287
TI  - Academic publishing: content, distribution, and access.

PMID- 9934288
TI  - Learning objectives for medical student education--guidelines for medical
      schools: report I of the Medical School Objectives Project.
AB  - Many observers of medicine have expressed concerns that new doctors are not as
      well prepared as they should be to meet society's expectations of them. To assist
      medical schools in their efforts to respond to these concerns, in January 1996
      the Association of American Medical Colleges (AAMC) established the Medical
      School Objectives Project (MSOP). The goal for the first phase of the project-
      which has been completed and is reported in this article--was to develop a
      consensus within the medical education community on the attributes that medical
      students should possess at the time of graduation, and to set forth learning
      objectives that can guide each medical school as it establishes objectives for
      its own program. Later reports will focus on the implementation phase of the
      MSOP. In this report, each of the four attributes agreed upon by a wide spectrum
      of medical educators is stated and explained, and then the learning objectives
      associated with the school's instilling of that attribute are stated. The first
      of the four attributes is that physicians must be altruistic. There are seven
      learning objectives, including the objective that before graduation, the student
      can demonstrate compassionate treatment of patients and respect for their privacy
      and dignity. The second attribute is that physicians must be knowledgeable; one
      of the six learning objectives is that the student can demonstrate knowledge of
      the normal structure and function of the body and of each of its major organ
      systems. The third attribute is that physicians must be skillful; one of the
      eleven learning objectives is that the student have knowledge about relieving
      pain and ameliorating the suffering of patients. The last attribute is that
      physicians must be dutiful; one of the six learning objectives is that the
      student have knowledge of the epidemiology of common maladies within a defined
      population, and the systematic approaches useful in reducing the incidence and
      prevalence of those maladies. The report ends by stating that (1) if a school's
      curriculum is shaped by the set of learning objectives presented in the report,
      the graduates will be well prepared to assume the limited patient care
      responsibilities expected of new residents and also will have begun to achieve
      the attributes needed to practice contemporary medicine; (2) schools should feel
      a sense of urgency in responding to the intent of the report; and (3) it is
      important to measure the outcomes of learning objectives, and better assessment
      methods should be developed, particularly ones to assess outcomes related to
      attitudes and values.

PMID- 9934289
TI  - Systems errors versus physicians' errors: finding the balance in medical
      education.
AB  - In recent years, identifying the origins of medical errors has been aided by a
      growing awareness that such errors are frequently the result of flaws in the
      system. In short, they are "accidents waiting to happen." Despite the value of
      the systems approach in identifying and preventing errors, it creates a difficult
      ethical problem for medical educators. Evidence suggests that when physicians
      ascribe errors to systemic causes, they may be less likely to modify their future
      behaviors and thus will be more likely to repeat past errors. Therefore, academic
      medical centers (i.e., teaching hospitals) must achieve a delicate balance that
      protects patients from the error that a systems approach can identify, yet
      provides optimal education for house officers by teaching them to focus also on
      personal reasons for errors. The authors suggest that this balance can be
      achieved by having residency programs work aggressively to remove the obstacles
      that house officers predictably encounter when they look for the personal causes
      of error (e.g., being shamed, feeling fear and inadequacy). Programs must also
      encourage house staff to disclose their errors and make constructive changes in
      their own behaviors, encouraged and guided by role models. The article concludes
      with discussion of these and related strategies to achieve the desired balance
      between the use of a systems approach and a personal-responsibility approach to
      managing errors in academic medical centers.

PMID- 9934290
TI  - How much neurology should a medical student learn? a position statement of the
      AAN Undergraduate Education Subcommittee.
AB  - Neurologic disease, already common in the United States, will become even more
      common in the future. But presently, neurology education at the undergraduate
      level and in primary care residencies is declining and does not adequately train
      physicians to manage neurologic illness. The authors maintain that this serious
      problem can be partially addressed by improving the neurology education of all
      primary care physicians and by allowing students access to neurology specialists.
      The education of medical students in the basic and clinical neurosciences must be
      integrated into a seamless curriculum over the four years of medical education.
      This education experience must be taught through a team approach and must be led
      by both a clinician and a basic scientist. All medical students must acquire the
      knowledge, skills, and attitudes necessary to perform an initial evaluation of
      the patient with a neurologic complaint. Finally, students must understand the
      role and recognize the importance of the neurologist and know when consultation
      is needed. This continuum of neurology education must be financially supported by
      the institution, and course leaders who show excellence in education must be
      rewarded with compensation and promotion.

PMID- 9934291
TI  - Primary care and psychiatry: anticipating an interfaith marriage.
AB  - The emergence of a managed-care--driven health delivery system in the United
      States has had a major impact on both primary care physicians and psychiatrists.
      Since a significant portion of psychiatric disorders present in primary care
      settings and a significant number of patients with emotional disorders receive
      their care from primary care physicians, the convergence of the two fields of
      medicine seems likely. Surveys document that both the diagnosis and the treatment
      of emotional disorders are inadequate in primary care. The authors review
      possible approaches to rectifying this situation and show that the attachment of
      the psychiatrist to the primary care team offers many advantages to the provision
      of clinical services, the education of a diverse group of trainees, and the
      collaboration of two categories of physician not typically seen as working
      closely together. The authors also describe an outpatient county medical clinic
      in which the concept of "attachment-liaison" of the psychiatrist to the primary
      care setting is tested on a daily basis. The authors (a psychiatrist and an
      internist), who met in this setting, detail their initial expectations and the
      observed outcomes of having a psychiatrist join the clinic team. The various
      tasks of the psychiatrist in this primary care setting are enumerated, along with
      several typical case presentations.

PMID- 9934292
TI  - Informing the teaching process: lessons from the educational sciences.
AB  - Until recently, most medical educators emphasized the art of medical education
      and largely ignored the fundamental science of learning underlying their basic
      practices. However, over the last decade medical education has evolved into an
      academic discipline in its own right, where scholarship can be demonstrated in
      the generation of new knowledge or the development of more efficient or effective
      strategies for transferring knowledge to others. It is essential that all medical
      educators familiarize themselves with the fundamental literature of the learning
      sciences and build upon it as it applies to their individual practices as medical
      teachers. Recent developments in the discipline of medical education and their
      implications for teaching will be the focus of this year's Ideas for Medical
      Education column. As associate editor for 1999, the author of this paper
      describes the problems associated with mastering the scientific underpinnings of
      medical education and outlines the kinds of questions that will be addressed in
      the Ideas feature throughout the year.

PMID- 9934293
TI  - Medical practice and informatics tools: a vignette.
AB  - In this article the authors recreate an improvisational vignette originally
      presented at the Third Annual Information Connection in Burlington, Vermont, in
      January 1998. The vignette illustrates various state-of-the-art decision-support
      systems for clinical care and their promises and problems in real-world medical
      practice. The characters are Dr. Alex Grant, a rural physician in solo practice;
      Anna Everett, a patient suffering from chronic headaches; Bob, a hospital
      librarian; and Sarah, Dr. Grant's nurse. The short play centers on Dr. Grant's
      attempt to diagnose the cause of Anna's headaches (which he and she believe to be
      sinus-related) and the roles information technologies--Medline searching, Anna's
      own Internet searches, the use of MDConsult, which provides Internet access to
      standard medical texts, journals, etc., and a desktop decision-support tool
      called Problem Knowledge Couplers--play in this process. The vignette concludes
      with the realization that while computer technologies can be of great help in
      medicine "there is still a need for a good doctor to pull it all together."

PMID- 9934294
TI  - Stories for a humanistic medicine.
AB  - In this first article for the feature Humanism and Medicine, Rita Charon
      introduces an excerpt from Richard Selzer's introduction to his latest book, The
      Doctor Stories. In her introductory and concluding comments, Charon contemplates
      the role of stories in medicine and how both truth and healing can be found in
      both listening to and telling stories. In the excerpt presented, surgeon and
      writer Selzer muses on his twin crafts. As a writer, Selzer can fully appreciate
      that which he witnesses in his life as a doctor. His ruminations on his own dual
      citizenship suggests that all doctors, perhaps, can deepen their commitment to
      medicine, to their patients, and to themselves by strengthening their capacity to
      behold their patients and to grasp their predicaments. Selzer also traces his
      origins and, by implication, projects his future. As practicing physicians and
      medical educators, readers of Academic medicine might be inspired to do the same.

PMID- 9934295
TI  - Avoiding casualties in the genetic revolution: the urgent need to educate
      physicians about genetics.

PMID- 9934296
TI  - Program directors' responses to a survey on variables used to select residents in
      a time of change.
AB  - PURPOSE: In an effort to gain information to give to students seeking to optimize
      their chances of attaining residency positions, the authors assessed actual and
      projected changes in the process to select residents and determined the relative
      weights that program directors assigned to academic and personal criteria.
      METHOD: In the fall of 1996, the authors mailed questionnaires to 1,200 program
      directors in 14 specialties requesting responses in four categories: current and
      projected changes in programs, current experiences with applicants and residents,
      the residency selection process, and the interview. RESULTS: Of those program
      directors, 794 (66.2%) responded. Nearly twice as many directors in university
      based hospitals projected decreases in residency positions over the next five
      years as did directors in university-affiliated hospitals. A significant
      percentage of specialties expected increased competition for positions. The
      authors observed a tight clustering of highly valued academic variables in the
      most competitive group of specialties. Some specialties admitted to using a first
      come, first-served basis for selecting candidates for interview. CONCLUSIONS: The
      study found significant changes in the process to select residents, including a
      decrease in residency positions, a continuation of this decrease, and a
      protracted escalation of competition for positions.

PMID- 9934297
TI  - The effects of differently weighting interview scores on the admission of
      underrepresented minority medical students.
AB  - PURPOSE: Seeking to admit medical students who will later practice medicine in
      underserved areas, but faced with the national debate over affirmative action
      programs, the authors evaluate the effects that giving different weightings to
      academic and interview scores have upon the acceptance or rejection of certain
      applicants. METHOD: The authors reviewed the admission records of 439 applicants
      to Texas A&M University College of Medicine in 1996-97. They compared the
      applicants actually admitted (accepted under a formula that equally weighted the
      two scores) with applicants who would have been admitted if the formula had
      weighted the interview scores at either 60% or 70% and the academic scores at
      either 40% or 30%. RESULTS: Weighting the academic score at 40% and the interview
      score at 60% produced little change in the make-up of the admissions. Weighting
      the academic score at 30% and the interview score at 70%, however, would have
      resulted in offers of acceptance to three additional underrepresented minority
      applicants, two of whom were disadvantaged students. CONCLUSION: Readjusting the
      weights of the criteria by which applicants are offered admission to medical
      schools may help meet the goal of educating doctors who will practice in
      underserved communities. More research must be done to explore other adjustments
      to admission criteria.

PMID- 9934298
TI  - Assessment of practicing family physicians: comparison of observation in a
      multiple-station examination using standardized patients with observation of
      consultations in daily practice.
AB  - PURPOSE: Looking for a valid, reliable, and feasible method to collect data on
      the performances of practicing family physicians, the authors compare the
      measurement characteristics of a multiple-station examination (MSE) using
      standardized patients with those of a video assessment of regular consultations
      in daily practice (practice video assessment, PVA). METHOD: In a cross-sectional
      study, consultations of 90 family physicians were videotaped both in an MSE and
      in their daily practices. Peer-observers used a validated instrument (MAAS
      Global) to assess the physicians' communication with patients and their medical
      performances. The physicians were randomly divided into two groups, comparable
      for demographic characteristics, and half underwent the assessments in reverse
      order to test for time-order effects. Content validity, criterion validity,
      reliability, and feasibility of the two methods were compared. RESULTS: Content
      validity of the PVA was superior to that of the MSE, since the domain of general
      family practice care was better covered. Observed participants judged the
      videotaped practice consultations to be "natural," whereas hardly any family
      physician, after reviewing the videotaped consultations of the MSE, recognized
      his or her usual working style. Specific criteria made it possible to standardize
      real practice. Concerning criterion validity, only the medical-performance
      components of the two methods correlated. No correlation was found for the
      communication components. Real-practice performance proved to be less influenced
      by observation than was performance during the MSE. The reliabilities of the two
      methods, expected to be better in the controlled MSE, were comparable. The
      administration of the PVA was more flexible, less costly, and better accepted by
      the family physicians than was that of the MSE. CONCLUSION: Assessment for
      quality improvement of family physicians' practices by video observation in daily
      practice is superior to video assessment in a simulated setting using
      standardized patients.

PMID- 9934299
TI  - Distilling the literature: a randomized, controlled trial testing an intervention
      to improve selection of medical articles for reading.
AB  - PURPOSE: To test whether an academic detailing intervention would improve journal
      reading among residents. METHOD: In 1995-96, the authors conducted a randomized
      controlled trial at two family medicine residencies in Missouri. Fifty-nine
      family practice residents were randomized into two groups identical in baseline
      characteristics; 29 received individual 15-minute educational presentations,
      based on academic detailing, that emphasized careful selection of medical journal
      articles for reading. The authors measured the percentage of important journal
      articles of which the residents were aware, the percentage of those they had read
      (either abstract only or the whole article), and the percentage of correctly
      answered knowledge questions. RESULTS: Despite randomization, the residents in
      the control group indicated on the pretest that they were more likely than were
      the residents in the intervention group to be aware of and to have read abstracts
      from selected articles. However, when comparing pretest with posttest results,
      the intervention group recalled 18.2% (95% CI, 2.0, 34.0) more articles and
      correctly answered 16.6% (95% CI 3.0, 29.9) more knowledge questions than did the
      control group. CONCLUSION: A brief intervention increased residents' recall of
      important articles and knowledge of those articles' conclusions.

PMID- 9934300
TI  - Using in-clerkship tests to identify students with insufficient knowledge and
      assessing the effect of counseling on final examination performance.
AB  - PURPOSE: To determine whether in-clerkship tests identify students with
      insufficient knowledge and whether counseling affects final examination pass
      rates. METHOD: The authors reviewed students' mean scores from two internal
      medicine clerkship tests at the Wright State University School of Medicine from
      February 1993 to July 1996. To determine the sensitivity and specificity of the
      tests for identifying students with insufficient knowledge, they compared
      students in the lowest quartile of clerkship test results with those who scored
      290 or less on the end-of-clerkship National Board of Medical Examiners' (NBME)
      subject examination in medicine. The authors also compared the final examination
      pass rates of counseled and non-counseled students. RESULTS: Twenty-five students
      scored 290 or less on the NBME subject examination. Of those, 17 had low mean
      clerkship test scores (sensitivity of 68%). The specificity of a low mean
      clerkship test score was 81%. Counseling did not improve final examination pass
      rates. CONCLUSION: In-clerkship tests can identify students who are at risk of
      failing an end-of-clerkship examination. Because counseling may be insufficient
      to raise final examination pass rates, further study into the appropriate
      clerkship intervention for low-achievement students is needed.

PMID- 9934301
TI  - Evaluating procedural skills competence: inter-rater reliability of expert and
      non-expert observers.
AB  - PURPOSE: To examine the inter-rater reliability of expert and non-expert
      observers when they used objective structured checklists to evaluate candidates'
      performances on three simulated medical procedures. METHOD: Simulations and
      structured checklists were developed for three medical procedures: endotracheal
      intubation, application of a forearm cast, and suturing a simple skin laceration.
      Groups comprised of two expert and two non-expert observers scored the
      performances of 101 procedures by 38 medical trainees and practitioners of
      varying skill levels. Inter-rater reliability was assessed using Pearson
      correlation coefficients. RESULTS: Inter-rater reliability was good for
      expert/expert, expert/non-expert, and non-expert/non-expert pairings in all three
      skills simulations. CONCLUSION: Both expert and non-expert observers demonstrated
      good inter-rater reliability when using structured checklists to assess
      procedural skills. Further study is required to determine whether this conclusion
      may be extrapolated to other study groups or procedures.

PMID- 9934302
TI  - Institutional change: embracing the initiative to train more generalists.
AB  - Dartmouth Medical School was one of 16 U.S. medical schools that received a
      Generalist Physician Initiative (GPI) grant from The Robert Wood Johnson
      Foundation in 1994. This article describes institutional change at the school,
      noting that while the context in which the GPI was launched was receptive, the
      grant enabled Dartmouth to accelerate institutional changes already under way.
      Perhaps even more important is that Dartmouth used an approach to change that
      worked, and although the specific actions may not generalize to other schools,
      the authors hope the principles will. Key among these principles were
      capitalizing on a sense of urgency for change, creating and empowering a guiding
      coalition, developing and communicating the vision, generating short-term wins,
      consolidating gains, and anchoring new approaches to the existing institutional
      culture. Changes at Dartmouth are described in the areas of admission and
      recruitment, undergraduate and graduate medical education, and supporting
      community practice. The authors also describe shortcomings in developing the
      program, such as maintaining the guiding coalition in the face of the changing
      health care system and clinical pressures, developing a vision and strategy in
      areas managed by the state, and engagement of a broad-based group.

PMID- 9934303
TI  - Promoting institutional change to encourage primary care: experiences at New York
      Medical College and East Carolina University School of Medicine.
AB  - New York Medical College and East Carolina University School of Medicine
      significantly changed their curricula and organizational structures in response
      to The Robert Wood Johnson Foundation's Generalist Physician Initiative (GPI).
      Seven common elements essential to successful institutional change were
      retrospectively identified at these two markedly different schools. They are (1)
      using national priorities to promote need for change, (2) establishing internal
      and external financial support, (3) developing a planning process and
      organizational structure to effect change, (4) devising an ongoing evaluation
      strategy, (5) sustaining positive attitudes toward primary care, (6) integrating
      community-based physicians, and (7) sustaining interest in the GPI. Within this
      framework, the authors present the GPI objectives at both schools, discuss
      examples of methods for institutional change and describe successes, failures,
      and lessons learned. The authors conclude that both schools have significantly
      increased the number of students choosing primary care careers and note the
      general perception of improvement in the quality of primary care educational
      programs, student recruitment, departmental collaboration, and faculty
      development opportunities. Although these changes have not yet been fully
      institutionalized, the similarities of the processes described may be of value to
      others addressing similar issues.

PMID- 9934304
TI  - The role of the generalist physician initiative in the merger of Hahnemann
      University and Medical College of Pennsylvania.
AB  - Unique in the history of academic medicine in the 20th century was the 1993
      merger of two medical schools, Hahnemann University and The Medical College of
      Pennsylvania, to create Allegheny University of the Health Sciences, the largest
      private medical school in the United States. During the early, most critical
      phase of the merger process, the two faculties were brought together to plan and
      submit an application for The Robert Wood Johnson Foundation's Generalist
      Physician Initiative (GPI). This action had a profound and lasting impact on the
      merger of the two schools and the educational enterprise that subsequently
      evolved. The GPI grant was awarded to the merged school in the midst of this
      complex merger rife with major changes, all with their attendant fears and
      frustrations. During and just after the merger, at a time when faculty and staff
      were somewhat uncertain about the direction of the university, the GPI provided a
      focus with a clear set of goals and objectives. Despite the unprecedented changes
      occurring in the organization and personal and professional concerns, faculties
      from the two institutions were able to join in pursuing the generalist initiative
      and its associated curriculum reform. This single, pervasive effort was a
      significant factor in forming a unified faculty of a united school of medicine.
      This sense of unity was put to the test when, in July 1998 the university, along
      with its affiliated hospital system, filed for bankruptcy. The goals of this
      extraordinary action were to sell the hospitals to another organization, thereby
      removing from the university the burden of supporting hospital-based clinical
      programs and allowing the university to emerge as a freestanding academic
      institution focusing on its core mission of education and the principles embodied
      in the GPI.

PMID- 9934305
TI  - The Virginia generalist initiative: lessons learned in a statewide consortium.
AB  - In response to Virginia's need for an increased supply of generalist physicians,
      the state's three medical schools--Eastern Virginia Medical School, Virginia
      Commonwealth University School of Medicine, and the University of Virginia School
      of Medicine--have formed a partnership with key governmental stakeholders in the
      Virginia Generalist Initiative funded by The Robert Wood Johnson Foundation's
      Generalist Physician Initiative. These state-supported medical schools
      historically have functioned independently, with little cooperative effort. This
      paper describes the consortium, its activities, its successes, and its unmet
      objectives, and uses a series of cases in point to illustrate relevant lessons
      learned. Some of these lessons are that (1) stakeholders must be involved from
      the beginning of planning to identify mutual goals and establish consortium
      protocols; (2) all partners must share a philosophical commitment to the
      consortium's mission, as well as the time and resources needed; (3) an atmosphere
      that enables risk-taking behavior must be created; (4) stakeholders must be
      willing to revise goals and sustain an environment conductive to change; and (5)
      trust is essential and must be vigilantly maintained. The paper concludes that
      the Virginia Generalist Initiative has dramatically altered the goals, objectives
      and programs of the three schools and has succeeded in aligning the schools'
      strategic objectives with the state's priorities.

PMID- 9934306
TI  - Use of a mini-grant program to stimulate generalist training at the University of
      Massachusetts Medical Center.
AB  - The authors describe and evaluate an annual competitive "mini-grant" program,
      funded by The Robert Wood Johnson Foundation's Generalist Physician Initiative
      established at the University of Massachusetts Medical School as a strategy to
      stimulate greater faculty involvement in the development of innovative,
      generalist-oriented projects. The mini-grant program stimulated proposals from
      across the academic community. The average award was small (mean = $7,039) but at
      times the awards led to results exceeding the scope of the original funding. In
      several cases, mini-grant support provided seed funding for faculty to undertake
      pilot projects to test new initiatives that would otherwise not have been
      developed. Some projects led to further ideas or to collaborations between
      generalists and basic scientists or specialists. More than half of funded
      projects were eventually institutionalized, and nearly 20% led to formal
      presentations at national meetings. Two problems are identified: (1) there were
      fewer proposals generated by specialist faculty and fewer collaborative proposals
      from generalists and specialists than anticipated, and (2) no funded proposals
      were generated by community-based faculty who were predominantly clinicians, such
      as preceptors. Despite these problems, and in light of available solutions, the
      authors conclude that an institutional mini-grant program can provide an ongoing,
      flexible mechanism to support a shift in institutional culture toward an enhanced
      status for generalism.

PMID- 9934307
TI  - The role of the medical school admission process in the production of generalist
      physicians.
AB  - Medical education research has identified a number of medical student
      characteristics that are related to graduates' entering generalist careers. These
      include initial specialty preference, geographic background, gender, age,
      ethnicity, economic and lifestyle factors, attitudes and personal values, service
      orientation, and premedical academic performance. Identifying and giving weight
      to these factors in the medical school admission process is likely to increase
      the number of graduates who choose generalist specialties. This paper discusses
      these medical student characteristics and presents strategies that medical
      schools could use in the selection process to enhance the matriculation of
      students who are most likely to become generalists. In this way, medical schools
      will be able to recruit and select students who are most likely to become
      excellent physicians, and also produce a more appropriate balance of all
      specialists to meet the needs of the population.

PMID- 9934308
TI  - Recruiting and selecting generalist-oriented students at New York Medical
      College.
AB  - This paper describes the strategies developed for student recruitment and
      selection at New York Medical College (NYMC), a private medical school with a
      consortium of 22 teaching hospitals, to meet its goal of 50% of graduating
      medical students entering generalist careers. With funding from The Robert Wood
      Johnson Foundation Generalist Physician Initiative, NYMC developed strategies to
      attract applicants interested in primary care and to select primary care
      applicants for matriculation. These strategies included use of recruiting
      newsletters to describe the primary care curriculum, on-campus open houses for
      undergraduates, visits to regional undergraduate schools by generalist faculty,
      changes in the admission committee to include more generalists, and changes in
      the interview format to stress nonacademic qualities in applicants. The authors
      present data from the Association of American Medical Colleges (AAMC) Pre-Medical
      Student Questionnaire and from the AAMC Medical School Matriculation
      Questionnaire that indicate NYMC achieved its objectives. They warn, however,
      that it is unclear whether these changes occurred solely as a result of NYMC's
      strategies, as a result of market forces driving career choices, or as a result
      of some combination of these factors.

PMID- 9934309
TI  - Recruiting and selecting generalist-oriented students at Pennsylvania State
      University College of Medicine.
AB  - The authors describe the strategies developed at the Pennsylvania State
      University College of Medicine, as part of The Robert Wood Johnson Foundation's
      Generalist Physician Initiative, to increase the proportion of graduating medical
      students entering generalist disciplines. These strategies included modifying the
      admission process to involve more primary care faculty so that students with
      identified potential for primary care would make up at least half of each
      entering class, and partnering with selected colleges and universities in
      Pennsylvania to increase the number of applicants with the potential for primary
      care. They describe partnering and outreach programs--Primary Care Day, off
      campus cluster meetings, and the Primary Care Scholars Program for college
      seniors--and present promising information about the results.

PMID- 9934310
TI  - Integrating early clinical experience curricula at two medical schools: lessons
      learned from the Robert Wood Johnson Foundation's Generalist Physician
      Initiative.
AB  - The University of Texas Medical Branch and Eastern Virginia Medical School have
      created community-based generalist clinical experiences early in the first two
      years of medical school as part of The Robert Wood Johnson Foundation's
      Generalist Physician Initiative. This article describes these experiences and
      related curricula, outlining the common elements and differing approaches at the
      two institutions. It discusses the success of the new curriculum, presenting
      information from performance measures and surveys of students, clerkship
      directors, and faculty involved in the programs, and it describes further
      evaluative studies being planned. The authors discuss nine lessons learned and
      their conclusion that early clinical experience with generalist physicians is an
      important element of generalist curriculum reform. It improves student
      satisfaction with the first two years' experience and provides a structure for
      teaching patient-centered, integrated clinical medicine, which is important in
      the general professional education of all students. Whether or not the long-term
      goal of increasing students' interest in generalist careers is realized,
      incorporating early clinical experiences with generalists into a curriculum has
      positive effects on students, faculty, and the overall curriculum.

PMID- 9934311
TI  - The impact of early clinical training in medical education: a multi-institutional
      assessment.
AB  - With funding from The Robert Wood Johnson Foundation's Generalist Physician
      Initiative, Dartmouth Medical School (DMS), New York Medical College (NYMC), and
      Virginia Commonwealth University School of Medicine (VCU-SOM) adopted early
      community-based training models for longitudinal clinical experiences. These
      schools developed different evaluation strategies to assess these models. This
      paper describes each program, the method used to evaluate an aspect of the
      program, lessons learned about early clinical teaching and learning, and
      challenges encountered. Each program used cross-sectional evaluation, and the
      analysis methods included descriptive statistics, chi-square, t-tests, analysis
      of variance, and generalized linear models. Dartmouth determined that the type of
      preceptor does not greatly influence the development of clinical skills, although
      case-specific differences were discovered. NYMC learned that students taught
      clinical skills in community-based settings performed as well as or better than
      their peers who received early patient experience on hospital wards. Virginia
      Commonwealth discovered that community experiences contributed positively to
      students' education, critical thinking, and problem-solving skills. Students
      value early clinical experiences and make important achievements in clinical
      skills and knowledge development, although logistic challenges exist in
      conducting these courses. Evaluations are critical to ensure competency, and
      faculty development must be linked to the evaluation process.

PMID- 9934312
TI  - Evaluating students on an interdisciplinary primary care clerkship at the
      Pennsylvania State University College of Medicine.
AB  - With funding from The Robert Wood Johnson Foundation's Generalist Physician
      Initiative, the Pennsylvania State University College of Medicine created a
      community-based primary care clerkship in general pediatrics, general internal
      medicine, and family and community medicine, in which third-year students spend a
      month in a small town, rural area, or urban underserved medical community. In
      addition to linking students with preceptors who would teach the clinical skills
      essential to primary care practice, the medical school set out to teach and to
      evaluate knowledge, attitudes, and behaviors unique to primary care. This paper
      describes the three-part teaching tool/evaluation developed to address (1) a
      student's recognition of the characteristics of primary care (learning objectives
      assignment), (2) a student's ability to appreciate the multiple nonmedical
      factors influencing a patient's health and experience of illness (family
      project), and (3) a student's ability to solve clinical problems (clinical
      reasoning examination). The authors describe how these evaluation methods are
      linked with the clerkship's goals and objectives and how they yield a richer
      portrait of the student's performance than the traditional preceptor's evaluation
      alone can provide. They also discuss the relationship between students'
      performances on the primary care clerkship and their performances in other
      clinical clerkships. Similar clinical experiences in primary care should focus on
      features unique to primary care medicine in both teaching and evaluation.

PMID- 9934313
TI  - Impact of a preceptor education board and computer network to engage community
      faculty at Dartmouth Medical School.
AB  - In 1994, as part of the Generalist Physician Initiative of The Robert Wood
      Johnson Foundation, Dartmouth Medical School established two programs to support
      and engage community-based teaching. The Preceptor Education Board and Community
      Computer Network were established to support a network of community-based
      preceptors and to facilitate communication between course directors at the school
      and community-based teachers. The board's mission is to organize, develop, and
      support a network of community-based primary care faculty, and to create and
      review community-based curricula. Through the board, community faculty members
      have made substantial contributions to curriculum, evaluation, faculty
      development, governance, and financing in community-based teaching. The Community
      Computer Network provides hardware, software, network systems, and support.
      Course directors and students have reported improved community-based educational
      experiences as a direct result of the Network. These two initiatives are dynamic
      and effective ways to improve the quality of community-based education and
      preceptors' morale. These efforts have strengthened the community faculty and
      their connection to the academic medical center.

PMID- 9934314
TI  - Faculty development for community-based physicians at the University of
      Massachusetts and SUNY-Buffalo.
AB  - Community-based faculty development (CBFD) is becoming increasingly important as
      medical education moves into the ambulatory/office-based setting CBFD provides
      preceptors with essential knowledge, skills, and attitudes directly related to
      teaching while providing a sense of identity as teachers to a diverse group of
      practitioners in a variety of settings. This article reviews the structure and
      function of successful community-based faculty development, using as examples
      programs from the University of Massachusetts Medical School and the State
      University of New York at Buffalo that were supported by The Robert Wood Johnson
      Foundation's Generalist Physician Initiative. After reviewing the literature on
      successful implementation of programs dedicated to community-based precepting,
      the authors investigate the educational concepts, instructional designs, and
      operational characteristics that are the framework for providing successful
      faculty development to community-based preceptors. They list rationales and
      examples of the educational methods used and compare structural components of the
      programs at both institutions. Last, they explore future directions in the
      rapidly changing medical education environment that need to be addressed in CBFD
      in the areas of outcome/program evaluation, comprehensive needs assessment, and
      regionalization.

PMID- 9934315
TI  - Performance of third-year primary-care-track students in an integrated curriculum
      at Case Western Reserve University.
AB  - In 1994, Case Western Reserve University School of Medicine established a Primary
      Care Track (PCT) with an integrated curriculum as part of The Robert Wood Johnson
      Foundation's Generalist Physician Initiative. This study compared the performance
      of the first cohort of students to participate in the PCT third year with that of
      their classmates and determined student attitudes toward their experiences. The
      performances of 24 PCT and 81 traditional students on the Medical School
      Admissions Test (MCAT) and the United States Medical Licensure Examination
      (USMLE) Step 1 and 2 were compared using analysis of variance. Grades on the six
      core clerkships were compared using chi-square analysis. Performances of the PCT
      students and a subset of traditional students on the generalist school's
      objective structured clinical exam (OSCE) were compared using multivariate
      analysis. The students reported their perceptions on a questionnaire. The
      traditional students had significantly higher scores on the physical science
      section of the MCAT and on the USMLE Step 1, but at the end of year three, their
      USMLE Step 2 scores did not differ. Grade distributions in the core clerkships
      did not differ, except in psychiatry, where the PCT students received honors
      significantly more often. The PCT students had a lower mean score on the internal
      medicine National Board of Medicine Examiners shelf exam but performed better on
      the generalist OSCE exam. A majority of PCT students reported that they would
      choose the integrated third year again and recommend it to others.

PMID- 9934316
TI  - The standardized family: an innovation in primary care education at the
      University of Massachusetts.
AB  - In 1995 as part of The Robert Wood Johnson Foundation's Generalist Physician
      Initiative, the University of Massachusetts (UMass) Medical School developed the
      "standardized family" as a new model for teaching the essential elements of
      primary care in a core curriculum format outside of the clinical setting. Using
      this model, a hypothetical family unit (the "McQ Family") serves as the focus for
      case-based clinical problem solving. This paper describes the standardized family
      model and provides two years of evaluation outcomes such as curriculum
      assessments, student performance outcomes, and correlation with external measures
      of clinical performance to support the effectiveness of this educational model.
      It discusses the transferability of the standardized family model from UMass
      Medical School to Pennsylvania State University College of Medicine and uses
      Pennsylvania State's adaptation (the "Hershey-Penn Family") to illustrate how the
      standardized family can be customized to integrate a core curriculum into a three
      year longitudinal primary care program. The authors suggest that the standardized
      family model has the potential to meet a broad range of primary care teaching
      needs at other institutions.

PMID- 9934317
TI  - Redesigning the surgery clerkship at MCP Hahnemann School of Medicine to address
      the educational needs of generalists.
AB  - This article describes how the surgery clerkship at MCP Hahnemann School of
      Medicine was redesigned to provide all students a well-rounded general
      professional education and to address the specific educational needs of
      generalists. During the 12-week clerkship, students spend eight weeks on two
      different general surgery rotations, which include significant experiences in
      outpatient settings. The evaluation and management of common general surgical
      problems, as well as the holistic approach to patient care, are emphasized. A
      nurse educator, recruited through funding obtained from The Robert Wood Johnson
      Foundation's Generalist Physician Initiative, provides formal instruction in
      holistic care and teaches bedside procedures. Two weeks are devoted to focused
      surgical subspecialty experiences addressing common conditions and are conducted
      primarily in outpatient settings. The remaining two weeks include an integrated
      musculoskeletal disease rotation, including orthopaedic surgery, rheumatology,
      physiatry, and radiology. Didactic teaching includes criteria for referral of
      patients from generalists to specialists. The new clerkship model has been well
      received by the students. Review of student logs for the first six months
      indicates the breadth of surgical experience has been maintained and appropriate
      balance achieved between simple and complex surgical cases. Further evaluation of
      the model will continue through longitudinal follow-up.

PMID- 9934318
TI  - A longitudinal ethics curriculum for medical students and generalist residents at
      the Medical College of Georgia.
AB  - Medical ethics is an important instructional area for both the undergraduate
      student pursuing a generalist education and generalist residents. With the
      support of a Generalist Physician Initiative (GPI) award from The Robert Wood
      Johnson Foundation, the Medical College of Georgia has implemented a longitudinal
      experience in clinical ethics spanning the four undergraduate years to make this
      area more meaningful and clinically relevant. This report outlines the structure
      and content of this four-year curriculum, which has been developed and
      implemented in a stepwise fashion since 1996. Course themes and students'
      activities during the four years are described. Since 1997, a shared curriculum
      in ethics--developed for residents in internal medicine, family medicine, and
      pediatric generalist programs--has been provided in combined interdepartmental
      conferences as part of a broader interdepartmental generalist curriculum. Early
      evaluation findings and plans for future evaluation programs are also described.

PMID- 9934319
TI  - Moving from policy to practice in curriculum change at the University of Virginia
      School of Medicine, East Carolina University School of Medicine, and SUNY-Buffalo
      School of Medicine.
AB  - A set of formative evaluation studies from the medical schools of the University
      of Virginia (UVA), East Carolina University (ECU), and the State University of
      New York at Buffalo (SUNY-Buffalo) portrays, in qualitative and quantitative
      terms, evidence of achievements and obstacles to the curricular reform supported
      by The Robert Wood Johnson Foundation's Generalist Physician Initiative (GPI). In
      this paper, innovations in the under-graduate curriculum, a specific course, and
      instructional strategies are examined. Individual interviews of faculty and focus
      groups with students assessed opinions about curricular change at the University
      of Virginia. Questionnaires and focus groups provided information about the
      impact of course changes at East Carolina University. Questionnaires completed by
      students provided information of the effect of modifying the instructional
      strategies at SUNY-Buffalo. The obstacles to implementing change at the three
      schools included breakdowns in the faculty's understanding and support of change,
      lack of skills required to implement change, and weakness in coordinating and
      assessing planned change. Although the GPI catalyzed changes in the content and
      conduct of generalist education at the three schools, many lessons were learned
      that are applicable to other medical schools.

PMID- 9934320
TI  - A statewide system to track medical students' careers: the Pennsylvania model.
AB  - In 1994 the Commonwealth of Pennsylvania announced a statewide Generalist
      Physician Initiative (GPI) modeled after The Robert Wood Johnson Foundation's
      GPI. Three-year grants totaling more than $9 million were awarded to seven of
      Pennsylvania's medical schools, including two that had already received GPI
      grants from the foundation. Stimulated by these initiatives, the state's six
      allopathic and two osteopathic medical schools decided to work together to
      develop a collaborative longitudinal tracking system to follow the careers of all
      their students from matriculation into their professional careers. This statewide
      data system, which includes information for more than 18,000 students and
      graduates beginning with the entering class of 1982, can be used to evaluate the
      impact of the Pennsylvania GPI, and it also yielded a local longitudinal tracking
      system for each medical school. This paper outlines the concept of the system,
      its technical implementation, and the corresponding implications for other
      medical schools considering the development of similar outcomes assessment
      systems.

PMID- 9934321
TI  - A combined residency in family medicine and internal medicine at Eastern Virginia
      Medical School.
AB  - This paper describes the first operational four-year combined family
      medicine/internal medicine residency designed to qualify residents for board
      examination in both disciplines, which began at Eastern Virginia Medical School
      in 1995. The authors describe key program features, including their block
      rotation schedule, interdisciplinary ambulatory precepting, and plans for
      achieving 50% ambulatory training experience, as well as their difficulties in
      implementing a collaborative core didactic experience. The authors present
      faculty survey data indicating that internal medicine faculty members are more
      likely to view the combined residency as a resource, while family medicine
      faculty members would like to concentrate on the categorical residency. A recent
      survey of combined residents indicates that they are satisfied with their choice
      of combined training and optimistic about the opportunity of garnering additional
      skills relative to their internal medicine and family medicine counterparts. The
      authors suggest that successfully implementing this interdisciplinary effort
      requires an atmosphere of mutual respect and an effort to find opportunities to
      positively affect the training experiences of both combined residents and their
      resident partners in family medicine and internal medicine.

PMID- 9934322
TI  - Increasing recruitment contacts between generalist residents at the Medical
      College of Georgia and rural and underserved communities.
AB  - To increase the number of residents choosing to practice in rural and underserved
      areas, the Medical College of Georgia in 1994 created the Office of Recruitment
      and Retention (ORR) for generalist physicians as part of its participation in The
      Robert Wood Johnson Foundation's Generalist Physician Initiative. Its major
      purpose is to increase the contact between generalist residents and practice
      opportunities, especially those in rural and underserved areas. The office has
      helped residents better understand the resources available in rural settings and
      has helped these communities better understand the needs of graduates in
      generalist residency programs. It became a point of contact for residents and
      communities. It also organized on-campus "practice opportunity fairs" that
      permitted community representatives to meet formally with generalist residents to
      provide information on practice opportunities and community resources. The office
      organized practice management sessions and provided legal consultation to
      residents desiring to enter private practice in rural settings. This program has
      already been instrumental in furthering contact between generalist residents and
      the rural communities they selected as clinical practice sites during training.
      Although it is too early to know the impact of these activities, communities
      increasingly use the office to recruit generalist physicians, and residents use
      it to identify appropriate practice sites.

PMID- 9934323
TI  - Debt management and financial planning support for primary care students and
      residents at Boston University School of Medicine.
AB  - Boston University Medical Center created the Office of Residency Planning and
      Practice Management as part of The Robert Wood Johnson Foundation's Generalist
      Physician Initiative. Since 1995, the office has improved the medical center's
      ability to promote and support the generalist career decisions of its students
      and residents by removing indebtedness as a disincentive. After a brief review of
      the relationship between indebtedness and specialty selection, the authors
      delineate the nature and volume of debt-management assistance provided by the
      office to students and residents through individual counseling sessions,
      workshops, and other means between April 1995 and March 1998. A case study shows
      the progression of these services throughout residency training. The medical
      center also coordinates its debt-management assistance with counseling from
      physician-oriented financial planning groups. In conclusion, the authors discuss
      several characteristics of a successful debt-management program for residents.

PMID- 9934324
TI  - Academic models for practice relief, recruitment, and retention at the University
      of New Mexico Medical Center and East Carolina University School of Medicine.
AB  - Locum tenens programs were independently developed by the University of New
      Mexico Health Sciences Center and East Carolina University School of Medicine to
      address health care needs within their states. The programs represent distinct
      models to provide locum tenens services for practices in rural and medically
      underserved regions through collaboration with stage government representatives
      and agencies. Differences between programs include years of operation, days of
      coverage provided, types of learners and providers involved, sources of funding,
      costs of the programs, and extent of institutional support. Common beneficial
      outcomes of the programs include coverage for struggling practices, training in
      rural medicine for locum tenens providers, recruitment of physicians to rural
      practice sites, and improved relationships with program partners. Adequate
      funding and institutional support are essential for success of locum tenens
      programs.

PMID- 9934325
TI  - Critical indicators about the workplace.

PMID- 9934326
TI  - Overcoming inner obstacles to career success.

PMID- 9934328
TI  - How to get a license.

PMID- 9934327
TI  - Career growth: combing the Web.

PMID- 9934329
TI  - Your guide to certification.

PMID- 9934330
TI  - Make way for the private sector.

PMID- 9934331
TI  - Is feverfew a pharmacologic agent?

PMID- 9934332
TI  - Kitchen-table medicine.

PMID- 9934333
TI  - Kitchen-table medicine.

PMID- 9934334
TI  - Kitchen-table medicine.

PMID- 9934335
TI  - Practical reasoning in Canada.

PMID- 9934336
TI  - "Revenge fantasy" has no place in medicine.

PMID- 9934337
TI  - The autonomy of elderly patients.

PMID- 9934338
TI  - The street life of drugs.

PMID- 9934339
TI  - The street life of drugs.

PMID- 9934340
TI  - The street life of drugs.

PMID- 9934341
TI  - Persistence with treatment for hypertension in actual practice.
AB  - BACKGROUND: Despite the existence of efficacious medications, many patients in
      actual practice remain with uncontrolled hypertension. Randomized clinical
      trials, cannot address this issue well given their highly restricted environment.
      This paper examines persistence with antihypertensive therapy among patients in
      actual practice. METHODS: Cohort study of patients who received a diagnosis of
      hypertension and were treated between 1989 and 1994 identified through the
      Saskatchewan Health databases. Patients with concurrent diagnoses likely to
      affect initial treatment choice were excluded. The resulting population of 79,591
      subjects was grouped into those with established hypertension (52,227 [66%]) and
      those with newly diagnosed hypertension (27,364 [34%]). The initial
      antihypertensive prescription, subsequent changes in treatment and persistence
      with antihypertensive therapy were analysed. RESULTS: Persistence with
      antihypertensive therapy decreased in the first 6 months after treatment was
      started and continued to decline over the next 4 years. Of the patients with
      newly diagnosed hypertension, only 78% persisted with therapy at the end of 1
      year, as compared with 97% of the patients with established hypertension (p <
      0.001). Among those with newly diagnosed hypertension, older patients were more
      likely than younger ones to persist, and women were more likely than men to
      persist (p < 0.001). INTERPRETATION: This analysis of actual practice data
      indicates that barriers to persistence occur early in the therapeutic course and
      that achieving successful therapy when treatment is started is important to
      maintaining long-term persistence.

PMID- 9934342
TI  - Effect of initial drug choice on persistence with antihypertensive therapy: the
      importance of actual practice data.
AB  - BACKGROUND: Rational medical decisions should be based on the best possible
      evidence. Clinical trial results, however, may not reflect conditions in actual
      practice. In hypertension, for example, trials indicate equivalent
      antihypertensive efficacy and safety for many medications, yet blood pressure
      frequently remains uncontrolled, perhaps owing to poor compliance. This paper
      examines the effect of initial choice of treatment on persistence with therapy in
      actual practice. METHODS: The authors examined all outpatient prescriptions for
      antihypertensive medications filled in Saskatchewan between 1989 and 1994 by over
      22,000 patients with newly diagnosed hypertension whose initial treatment was
      with a diuretic, beta-blocker, calcium-channel blocker or angiotensin-converting
      enzyme (ACE) inhibitor. Rates of persistence over the first year of treatment
      were compared. RESULTS: After 6 months, persistence with therapy was poor and
      differed according to the class of initial therapeutic agent: 80% for diuretics,
      85% for beta-blockers, 86% for calcium-channel blockers and 89% for ACE
      inhibitors (p < 0.001). These differences remained significant when age, sex and
      health status in the previous year were controlled for. Changes in the
      therapeutic regimen were also associated with lack of persistence.
      INTERPRETATION: A relation not seen in clinical trials--between persistence with
      treatment and initial antihypertensive medication prescribed--was found in actual
      practice. This relation also indicates the importance of real-world studies for
      evidence-based medicine.

PMID- 9934343
TI  - Current and projected annual direct costs of screening asymptomatic men for
      prostate cancer using prostate-specific antigen.
AB  - BACKGROUND: Concern over the cost of screening for asymptomatic prostate cancer
      by means of prostate-specific antigen (PSA) testing has played an important role
      in PSA screening policy. However, little is known about the true costs of current
      PSA screening in Canada and how costs may change in the future. METHODS: The
      authors performed a cost identification study from the perspective of provincial
      ministries of health. They used data from published reports, hospital discharge
      data, claims data from several provinces, a laboratory survey, a national survey
      of knowledge, attitudes and beliefs about screening, a provincial cancer registry
      and expert opinion to estimate current first-year screening costs. Using
      demographic data from Statistics Canada and various scenarios regarding changes
      in screening patterns, the authors derived estimates of the future costs of PSA
      screening. RESULTS: In 1995 PSA screening cost an estimated $45 million (range
      $40 million to $84 million). Treatment accounted for over 61% of total costs,
      whereas screening, diagnosis and staging accounted for 35%. Screening all
      eligible men in Canada in 1995 would have cost $317 million (range $356 million
      to $691 million), more than the costs of all prostate cancer care in that year.
      Annual recurrent screening for all eligible men in 2005 would cost $219 million
      (range $208 million to $412 million). Projections from existing trends suggest
      that annual costs of PSA screening in 2000 are likely to increase from the
      estimated $45 million to approximately $66 million (range $59 million to $126
      million). INTERPRETATION: PSA screening is costly, but even universal screening
      would consume a smaller share of national health expenditures than previous
      studies have suggested. Costs attributable to PSA screening may increase in the
      future owing to changes in utilization patterns and demographic shifts.

PMID- 9934344
TI  - Medical thunder is required to stir the Chretien government.

PMID- 9934345
TI  - Access to medical and health information in the developing world: an essential
      tool for change in medical education.

PMID- 9934346
TI  - Compliance in hypertension: why don't patients take their pills?

PMID- 9934347
TI  - Impact of new technologies in medicine: progress and pitfalls.

PMID- 9934348
TI  - Entering "the left atrium".

PMID- 9934349
TI  - Prostate-specific antigen testing in Ontario: reasons for testing patients
      without diagnosed prostate cancer.
AB  - BACKGROUND: The use of the prostate-specific antigen (PSA) test has been
      increasing rapidly in Canada since its introduction in 1988. The reasons for
      using the PSA test in patients without known prostate cancer are unclear. This
      paper reports on the first study in Canada to use physician records to assess the
      use of PSA testing. METHODS: A questionnaire was mailed to physicians attending
      475 patients without diagnosed prostate cancer. The patients were randomly
      selected from 2 laboratory databases of PSA test records in the greater Toronto
      area during 1995. The physicians were asked to consult their patient records to
      avoid recall bias. Information obtained included physician's specialty, patient's
      age at time of PSA test and reason(s) for the test. RESULTS: There were 264
      responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95%
      confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen
      for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary
      symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical
      procedure or drug therapy. More than one reason was permitted. Of 151 responses
      indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that
      it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part
      of a routine examination. For 19%, both investigation of symptoms and screening
      asymptomatic patients were given as reasons for testing, and for another 19% both
      follow-up of a medical procedure and screening were given as reasons. Screening
      was recorded as a reason for testing far more commonly for patients seen by
      family physicians and general practitioners than for patients seen by urologists
      (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary
      symptoms was more common for patients seen by urologists than for those seen by
      family physicians and general practitioners (52% v. 37%, p = 0.044). No
      significant difference was found between physician groups in the use of PSA
      testing as a follow-up of a medical procedure (42% for urologists and 31% for
      family physicians and general practitioners). About 24% of the PSA test records
      were for patients younger than 50 and older than 70 years. PSA testing initiated
      by patients was more common in the practices of family physicians and general
      practitioners than in the practices of urologists (44% v. 13%, p < 0.001).
      INTERPRETATION: Screening for prostate cancer was the most common reason for PSA
      testing in our study group; it occurred most commonly in the family and general
      practice setting and was usually initiated by the patient. Differences in reasons
      for testing were identified by practice specialty. Although PSA screening for
      prostate cancer is sometimes recommended for men between 50 and 70 years of age,
      it is being conducted in men outside this age group.

PMID- 9934352
TI  - Motivating patients to change.

PMID- 9934351
TI  - The big chill: diseases exacerbated by exposure to cold.

PMID- 9934350
TI  - Prostate cancer: 8. Urinary incontinence and erectile dysfunction.

PMID- 9934354
TI  - Chronic pain: primary care treatment of the older patient.
AB  - The prevalence of chronic diseases associated with pain increases with age, and
      pain prevalence appears to increase with the level of functional dependence.
      Chronic pain in older patients is associated with sleep disorders, impaired
      physical and social function, and increased healthcare utilization. Symptoms of
      pain, anxiety, and depression are often associated and may intensify each other.
      Because a complete resolution of chronic pain is unlikely, it is important to
      establish early in therapy the level of pain that the patient would find
      acceptable. The goal of therapy is to treat chronic pain while minimizing side
      effects and optimizing the patient's functional status.

PMID- 9934355
TI  - Genetics: an explosion of knowledge is transforming clinical practice.
AB  - Genetics is considered by many to be the field in which the next revolution in
      medicine will occur. The Human Genome Project, which is an effort to map the
      entire sequence of human DNA, is already leading to better diagnostics and
      therapeutics for clinical medicine. The ultimate goal of genetic medicine is to
      learn how to prevent disease or to treat it with gene therapy or a drug developed
      specifically for the underlying defect. Other applications include
      pharmacogenomics and patient counseling about individual health risks, which will
      be facilitated by new DNA chip technology. Concerns include how to integrate
      genetic technology into clinical practice and how to prevent genetic-based
      discrimination. A new coalition is being developed to educate health
      professionals about genetic medicine.

PMID- 9934353
TI  - Geriatrics photo quiz. Dermatologic signs of syphilis.

PMID- 9934356
TI  - Slowly darkening lesion on the face.

PMID- 9934357
TI  - Effectiveness of bacillus Calmette-Guerin (BCG) vaccination in the prevention of
      leprosy; a case-finding control study in Nagpur, India.
AB  - A hospital-based, pair-matched, casecontrol study was carried out at Government
      Medical College Hospital in Nagpur in central India to estimate the effectiveness
      of BCG vaccination in the prevention of leprosy. The study included 314 incidence
      cases of leprosy [diagnosed by World Health Organization (WHO) criteria] below
      the age of 32 years. Each case was pair matched with one control for age, sex and
      socioeconomic status. Controls were selected from subjects attending this
      hospital for conditions other than tuberculosis and leprosy. A significant
      protective association between BCG and leprosy was observed (OR 0.29, 95% CI 0.21
      0.41). The vaccine effectiveness (VE) was estimated to be 71% (95% CI 59-79). The
      BCG effectiveness against multibacillary and paucibacillary leprosy was 79% (95%
      CI 60-89) and 67% (95% CI 45-78), respectively. It was more effective during the
      first decade of life (VE 74%; 95% CI 38-90), among females (VE 82%; 95% CI 64
      90), and in the lower socioeconomic strata (VE 75%; 95% CI 32-92). The prevented
      fraction was calculated to be 51% (95% CI 38-62). In conclusion, this study has
      identified a beneficial role of BCG vaccination in the prevention of leprosy in
      central India.

PMID- 9934358
TI  - Delayed-type hypersensitivity reactions followed by erythema nodosum leprosum.
AB  - Reported herein are 13 borderline lepromatous (BL) or subpolar lepromatous (LLs)
      patients who presented with or developed delayed-type hypersensitivity (DTH)
      reactions after initiation of antibacterial therapy, but who subsequently
      developed erythema nodosum leprosum (ENL), the DTH to ENL group. During the same
      time, three LLs patients had ENL followed by relapse-associated DTH, a
      significant (p < 0.05) difference in sequence of the two conditions. The DTH to
      ENL group had statistically significant higher biopsy indexes at the time of
      diagnosis of the DTH reaction compared with two DTH control groups, 7
      multibacillary patients presenting with DTH reactions and 15 BL or LLs who
      developed DTH reactions after starting treatment but had no ENL. DTH-associated
      histologic changes were less well developed in the DTH to ENL group than in
      either of the two control groups. In the DTH to ENL group, 77% required
      prednisone in addition to thalidomide to achieve a complete remission in contrast
      to only 10% of 21 ENL clinical controls. In the DTH to ENL group, the classical
      histologic ENL pattern was present in only 31% of these patients, in contrast to
      88% of 33 ENL histologic controls. In 9 of 9 of the DTH to ENL patients studied,
      after the ENL remitted, Mycobacterium leprae-sonicate-stimulated lymphocyte
      transformation tests gave stimulation indexes within the range of our tuberculoid
      (TT) and borderline tuberculoid (BT) patients, in contrast to absent responses in
      6 ordinary, longterm-treated patients who had had ENL.

PMID- 9934359
TI  - The nose in leprosy: immunohistology of the nasal mucosa.
AB  - A detailed study of the nose was undertaken in 40 leprosy patients with different
      classifications of leprosy and different durations of disease at two hospitals in
      Brazil. This manuscript describes the immunohistochemical data on cellular
      infiltrates in the nasal biopsies of those patients. It was surprising that the
      damage to the whole depth of the nasal mucosa, epithelium and lamina propria was
      considerable, as was the case in the nasal mucosa which looked relatively normal
      during clinical inspection. The epithelium showed large holes which looked like
      very extended goblet cells. Very obvious was the lack of vasoconstriction after
      cocaine application, and the vessels also showed a lack of staining with factor
      VIII, possibly indicating a disruption of the endothelium. The number of
      neurofilaments was extensively reduced in all leprosy groups compared to normal
      controls. As in the skin, an increased number of CD68+ cells was found in the
      lamina propria of the nasal mucosa of the lepromatous patients. Contrary to
      findings in the skin, in the nasal mucosa of the borderline/lepromatous patients
      the number of CD4+ cells was increased and the number of CD8+ cells was decreased
      compared to normal controls. The number of CD8+ cells tended to be more reduced
      when the history of leprosy was longer. It is not clear as yet whether the
      reduced numbers of CD8+ cells are acquired during infection or whether persons
      with a low number of CD8+ cells in the nose might have a higher risk of acquiring
      leprosy.

PMID- 9934360
TI  - Contribution of type 1 reactions to sensory and motor function loss in borderline
      leprosy patients and the efficacy of treatment with prednisone.
AB  - The changes in nerve function tests in 297 new leprosy patients over an average
      period of 30 months were measured. The impact of type 1 reactions (T1R) on
      sensory and voluntary muscle function was measured by standard tests. Sensory
      function was improved in patients with single episodes of cutaneous T1R, but not
      improved in patients with neural T1R or with multiple episodes of either kind of
      T1R. Patients over 40 years of age improved less than younger patients, and
      patients admitted for treatment of T1R improved more than those treated as
      outpatients. These data point to a need to find better regimens for the treatment
      of nerve damage in T1R.

PMID- 9934361
TI  - Quantitative assessment of facial sensation in leprosy.
AB  - The trigeminal and great auricular nerves which supply sensation to the face are
      affected in leprosy. No objective sensory testing methods have been devised for
      testing sensation in the face. Testing for corneal sensation to ascertain
      trigeminal nerve or visualization and palpation of the great auricular nerve
      alone may not be enough to establish the involvement of these nerves. In a sample
      of leprosy patients, face sensation threshold measurements were done using a set
      of three Semmes-Weinstein (SW) monofilaments that gave a force of 0.05-0.07, 0.2
      and 2 g. Sensation was tested by three examiners and intra- and inter-observer
      testing was used as a means to validate the findings. Within the limitations of
      this study, the results indicate that use of SW monofilaments is a fairly
      reliable and repeatable method for sensory testing in the face. During follow up,
      a single filament with a force of 0.5-0.7 g (2.83 marking number in SW filament
      or any other filament with a corresponding gram force) could be used to assess
      sensation. A simple procedure of quantifying sensation in these nerves is
      suggested. A method to incorporate trigeminal or great auricular nerve sensory
      testing into the existing sensory assessment charts is also discussed.

PMID- 9934362
TI  - Assessment of anti-PGL-I as a prognostic marker of leprosy reaction.
AB  - The anti-phenolic glycolipid-I (PGL-I) assay as currently applied for leprosy is
      conceived as an early marker of asymptomatic infection, early disease diagnosis
      and cure monitoring. Its use as a prognostic marker of reaction is still a matter
      of controversy. We conducted a case-control study to investigate whether IgM and
      IgG anti-PGL-I antibodies could discriminate patients at increased risk of
      developing reactions. Eligible cases were untreated leprosy patients at the onset
      of type 1 and type 2 reactions recruited from among 600 concurrent, newly
      detected, untreated leprosy patients attending an outpatient clinic in central
      Brazil. For the patients with reaction, approximately the same number of leprosy
      cases without reaction matched as to bacterial index (BI), age and gender were
      randomly selected. Individuals without clinical leprosy were evaluated as healthy
      controls. Sera from type 1 reaction (N = 43) and type 2 reaction (N = 26)
      patients were tested by an ELISA using PGL-I synthetic disaccharide-BSA antigen
      and 1:300 sera dilution (cut-off point > or = 0.2 OD). Antibody profiles were
      evaluated by exploratory data analysis and reverse cumulative distribution
      curves. The IgG anti-PGL-I response did not have a defined pattern, being
      detected only at low levels. Our results indicate that leprosy patients,
      independently of their reactional status, produce high levels of IgM anti-PGL-I,
      demonstrating a strong correlation between the magnitude of antibody response and
      the BI. Patients with a higher BI were at least 3.4 times more prone to produce
      an antibody response compared to healthy controls.

PMID- 9934364
TI  - Anti-contagionism in leprosy, 1844-1897.

PMID- 9934363
TI  - Mycobacterium lepraemurium, a well-adapted parasite of macrophages: I. Oxygen
      metabolites.
AB  - We measured the release of reactive oxygen intermediaries [ROI (hydrogen peroxide
      and superoxide anion)] by murine peritoneal macrophages challenged in vitro with
      Mycobacterium lepraemurium (MLM), complement-opsonized yeast, M. bovis BCG, M.
      phlei, or phorbol myristate acetate (PMA). We found that except for MLM, all of
      the other materials provoked the release of significant amounts of hydrogen
      peroxide and superoxide. MLM entered the macrophages without triggering their
      oxidative metabolism. Pre-infection of macrophages with MLM did not alter these
      cells' capacity to release the normal amounts of ROI in response to other
      microorganisms or PMA. Killing of MLM did not revert the macrophages' failure to
      release ROI upon ingestion of the microorganism, nor were macrophages able to
      produce these toxic metabolites when pre-incubated in the presence of murine
      gamma interferon (IFN-gamma). MLM has several attributes that allow it to survive
      within macrophages: a) it is a nontoxigenic microorganism (it does not harm its
      host), b) it resists the harsh conditions of the intraphagolysosomal milieu (a
      property perhaps dependent on its thick lipidic envelope), and c) it penetrates
      the macrophages without triggering their oxidative response (thus avoiding the
      generation of the toxic intermediaries of oxygen). For these attributes (and
      others discussed in this paper), we recognize MLM as a highly evolved, well
      adapted parasite of macrophages. In addition, the results of the present study
      prompted the analysis of the biochemical pathways used by MLM and M. bovis BCG to
      penetrate into their cellular hosts, a subject now under investigation in our
      laboratory.

PMID- 9934365
TI  - Lepromatous orchitis associated with seminoma.

PMID- 9934366
TI  - beta2-Glycoprotein I-dependent anticardiolipin antibodies as risk factor for
      reactions in borderline leprosy patients.

PMID- 9934367
TI  - The primary lesion in leprosy.

PMID- 9934369
TI  - Acute sinusitis and the common cold.

PMID- 9934368
TI  - Relapse of multibacillary leprosy after treatment with daily rifampin plus
      ofloxacin for four weeks.

PMID- 9934370
TI  - Corneal abrasions need not be patched.

PMID- 9934371
TI  - Oral versus vaginal administration of misoprostol for labor induction.

PMID- 9934372
TI  - Alternative therapy for low back pain.

PMID- 9934373
TI  - Therapeutic touch and osteoarthritis of the knee.

PMID- 9934374
TI  - Nebulized ipratropium for children with acute asthma.

PMID- 9934375
TI  - D-dimer testing in suspected DVT.

PMID- 9934376
TI  - Initial treatment of generalized convulsive status epilepticus.

PMID- 9934377
TI  - A comparative analysis of antidepressants and stimulants for the treatment of
      adults with attention-deficit hyperactivity disorder.
AB  - BACKGROUND: Adults who identify themselves as having problems with attention and
      concentration will often make an office visit to request treatment with a
      stimulant medication, rather than an antidepressant. The uncertainty of the
      diagnosis and the prospect of a long-term prescription with a stimulant
      medication can create a dilemma for physicians. METHODS: We searched MEDLINE for
      any English-language studies of antidepressant or stimulant treatment of adults
      with attention deficits. References from relevant articles were reviewed to
      supplement the MEDLINE search. RESULTS: Antidepressants and stimulants seem to be
      equally effective for adults with attention-deficit hyperactivity disorder
      (ADHD). Recent controlled studies suggest that desipramine (an antidepressant)
      may be as effective as methylphenidate (a stimulant) for improving symptoms of
      adult ADHD. CONCLUSIONS: Although few good controlled studies exist, the
      available research suggests that certain antidepressants and stimulants are
      equally effective for adults with ADHD. Antidepressants may offer a safe first
      line treatment for adults with ADHD.

PMID- 9934378
TI  - What is so good about being the best?

PMID- 9934379
TI  - Malpractice claims against family physicians are the best doctors sued more?
AB  - BACKGROUND: Physicians who have been sued multiple times for malpractice are
      assumed to be less competent than those who have never been sued. However, there
      is a lack of data to support this assumption. Competence includes both knowledge
      and performance, and there are theoretical reasons to suspect that the most
      knowledgeable physicians may be sued the most. METHODS: We conducted a
      retrospective cohort study of family physicians who were included in the Florida
      section of the 1996 American Medical Association's Physician Masterfile and who
      practiced in Florida at any time between 1971 and 1994 (N = 3686). The main
      outcome was the number of malpractice claims per physician adjusted for time in
      practice. Using regression methods, we analyzed associations between malpractice
      claims and measures of physician knowledge. RESULTS: Risk factors for malpractice
      claims included graduation from a medical school in the United States or Canada
      (incidence rate ratio [IRR] 1.8; 95% confidence interval [CI], 1.6-2.1),
      specialty board certification (IRR 1.8; 95% CI, 1.6-2.1), holding the American
      Medical Association Physician's Recognition Award (IRR 1.4; 95% CI, 1.2-1.7), and
      Alpha Omega Alpha Honor Society membership (IRR 1.8; 95% CI, 1.1-3.0). Among
      board-certified family physicians, sued physicians who made no payments to a
      plaintiff had higher certification examination scores than nonsued physicians
      (53.48 vs 51.38, P < .01). The scores of sued physicians who made payments were
      similar to those of nonsued physicians (51.05 vs 51.38, P = .93). CONCLUSIONS:
      Among Florida family physicians, the frequency of malpractice claims increased
      with evidence of greater medical knowledge.

PMID- 9934380
TI  - The impact of physician practice style on medical charges.
AB  - BACKGROUND: There are differences in styles of care among primary care
      physicians. The purpose of our study was to determine whether differences in
      physician practice styles and patient health status generate different medical
      charges. METHODS: New adult patients (N = 509) were randomized to primary care
      physicians, and use of medical care services and associated charges were
      monitored for 1 year. RESULTS: Controlling for baseline patient health status, a
      technically oriented style of care was associated with significantly higher
      specialty care, emergency department, diagnostic, and total charges. Some
      practice behaviors, however, were associated with lower charges; for example, a
      practice style emphasizing patient activation was associated with significantly
      lower primary care charges. Both a lower baseline patient health status and a
      health status that declined over the study period predicted higher charges.
      CONCLUSIONS: Measurable differences in practice style are associated with
      differing medical care charges. Patients' health status was also an important
      determinant of medical charges and had implications for the assessment of
      physician utilization patterns.

PMID- 9934381
TI  - Primary care physicians' perceptions of diabetes management. A balancing act.
AB  - BACKGROUND: Studies demonstrate significant shortfalls in the quality of care for
      diabetes. Primary care physicians' views of the management of diabetes have been
      inadequately explored. The objective of our study was to describe primary care
      physicians' attitudes toward diabetes, patients with diabetes, and diabetes care.
      METHODS: In-depth interviews were conducted by a trained research interviewer
      with a sample of 10 family physicians and 9 internists in Connecticut. Interviews
      lasted an average of 60 minutes and were audiotaped and transcribed. Data were
      interpreted by a multidisciplinary team using a standard qualitative text
      analysis methodology. Themes from each interview were used to identify and
      develop overall themes related to the areas of inquiry. RESULTS: Physicians'
      goals were congruent with current guidelines emphasizing the importance of good
      glycemic control and prevention of complications. However, physicians noted the
      challenge of balancing the multiple goals of ideal diabetes care and the
      realities of patient adherence, expectations, and circumstances. The majority of
      physicians described a patient-centered management style, but a substantial
      minority described a more paternalistic approach. Physicians did not identify or
      describe office systems for facilitating diabetes management. Differences between
      family physicians and internists did not emerge. CONCLUSIONS: The complexity of
      diabetes care recommendations coupled with the need to tailor recommendations to
      individual patients produces wide variation in diabetes care. Improvement in care
      may depend on (1) prioritizing diabetes care recommendations for patients as
      individuals, (2) improving physicians' motivational counseling skills and
      enhancing their ability to deal with challenging patients, and (3) developing
      office systems and performance enhancement efforts that support cost-effective
      practice and patient adherence.

PMID- 9934382
TI  - Treatment of recurrent otitis media after a previous treatment failure. Which
      antibiotics work best?
AB  - BACKGROUND: Recurrent infection after an episode of otitis media is common in
      pediatric patients. If a patient experienced primary treatment failure in a
      preceding episode, physicians often feel pressured to prescribe a broad-spectrum,
      second-line agent for the next episode rather than a first-line drug. The purpose
      of our study was to determine whether using a second-line drug resulted in fewer
      treatment failures in a recurrent otitis episode following an episode of apparent
      resistance. METHODS: The Practice Partner Research Network database, a national
      research network of practices that use the same electronic medical record, was
      reviewed to identify all primary episodes of otitis media over a 2-year period (N
      = 7807). From this, 1416 pediatric patients with presumed treatment failures were
      identified. The subset of those with a second otitis media episode more than 90
      days after the index episode (N = 343) was selected for study. Of this group, 236
      (69%) received first-line antibiotics (amoxicillin, ampicillin, penicillin, or
      sulfamethoxazole-trimethoprim) and the remaining 107 received a broader-spectrum,
      second-line antibiotic. The primary outcome was the need for an additional
      antibiotic for otitis media within the next 45 days. RESULTS: Patients receiving
      first- and second-line antibiotics did not differ in sex or age. However, those
      receiving second-line antibiotics had a shorter duration between episodes (231 vs
      280 days, P = .007). Failure rates for first- and second-line antibiotics in
      recurrent episodes were not significantly different (13% vs 19%, P = .20).
      Because the duration between episodes could have affected failure rates, we
      stratified the time between episodes into short, intermediate, and long duration.
      Second-line antibiotics were not superior to first-line drugs in any stratum.
      CONCLUSIONS: For a new otitis media episode in a patient with a previous
      treatment failure, first-line drugs (amoxicillin, ampicillin, penicillin, or
      sulfamethoxazole-trimethoprim) are just as effective as broader-spectrum, more
      expensive, second-line antibiotics.

PMID- 9934383
TI  - Why don't men seek help? Family physicians' perspectives on help-seeking behavior
      in men.
AB  - BACKGROUND: Men tend to underuse primary care health services despite their
      susceptibility to particular types of illness. The purpose of this study was to
      report the family physician's perspective on why men do not access the health
      care system for medical problems. METHODS: We used focus group interviews to
      identify major themes. The participants were family physicians in active practice
      randomly selected from a list of 500 full- and part-time teachers. Four focus
      groups were formed from 18 participants (12 men, 6 women), in practice an average
      of 17 years. Eleven of the physicians were in community practice. RESULTS: Three
      key themes were identified: (1) Support: Men appear to get most of their support
      for health concerns from their female partners, little from their male friends.
      Their pattern of seeking support tends to be indirect rather than
      straightforward. (2) Help Seeking: Perceived vulnerability, fear, and denial are
      important influences on whether men seek help. They look for help for specific
      problems rather than for more general health concerns. (3) Barriers: Personal
      barriers involved factors related to a man's traditional social role
      characteristics: a sense of immunity and immortality; difficulty relinquishing
      control; a belief that seeking help is unacceptable; and believing men are not
      interested in prevention. Systematic barriers had to do with time and access;
      having to state the reason for a visit; and the lack of a male care provider.
      CONCLUSIONS: Many of these findings are supported by psychological theories.
      Future research should apply these theories in more transferable populations and
      settings. However, an in-depth understanding of the patterns of men's use of
      primary care services is needed before we can determine if a regular source of
      primary care would have a positive impact on their health.

PMID- 9934384
TI  - Family practice and the advancement of medical understanding. The first 50 years.
AB  - In the last half of the twentieth century, family practice has emerged as a
      strong influence in both community practice and academic medical centers. Since
      the formation in 1947 of the American Academy of General Practice, family
      practice has changed from a group of physicians applying the knowledge of other
      disciplines into a recognized specialty with its own body of learning. Family
      medicine has advanced medical understanding in: (1) relationship-based health
      care as the foundation of a specialty; (2) the process of comprehensive clinical
      reasoning; (3) the recognition of problems of living as a health care concern;
      (4) the meanings of words such as pain, disease, and disability; (5) the systems
      approach to primary health care; and (6) the clinical encounter as the definable
      unit of family practice. These 6 concepts have helped expand the specialty's body
      of knowledge and clarify its values. They will also serve as a template for the
      future evolution of family practice as the specialty faces new challenges,
      including managed care, the aging population, the rapid growth of medical
      knowledge, and the increased use of computers and technology in health care.

PMID- 9934385
TI  - Readability levels of patient education material on the World Wide Web.
AB  - BACKGROUND: Patient education is an important component of family practice.
      Pamphlets, verbal instructions, and physicians' self-created materials have been
      the most common resources for patient education. Today, however, the popularity
      of the World Wide Web (Web) as a ready source of educational materials is
      increasing. The reading skills required by a patient to understand that
      information has not been determined. The objective of our study was to assess the
      readability of medical information on the Web that is specifically intended for
      patients. METHODS: An investigator downloaded 50 sequential samples of patient
      education material from the Web. This information was then evaluated for
      readability using the Flesch reading score and Flesch-Kinkaid reading level.
      RESULTS: On average, the patient information from the Web in our sample is
      written at a 10th grade, 2nd month reading level. Previous studies have shown
      that this readability level is not comprehensible to the majority of patients.
      CONCLUSIONS: Much of the medical information targeted for the general public on
      the Web is written at a reading level higher than is easily understood by much of
      the patient population.

PMID- 9934386
TI  - The family physician and house calls. A survey of Colorado family physicians.
AB  - BACKGROUND: Visiting patients at home has long been one of the activities of the
      family physician, but the practice of making house calls has diminished
      significantly during the second half of the 20th century. The goal of this study
      was to describe physicians' attitudes about house calls and their practice of
      making them in the rapidly changing health care environment of the United States.
      METHODS: A 30-item, self-administered questionnaire was designed to obtain
      demographic information about physicians and their attitudes toward house calls,
      practice experiences with making house calls, and any additional factors that
      influence making house calls. It was mailed to all members of the Colorado
      Academy of Family Physicians, during the summer of 1997. RESULTS: A 66% response
      rate was obtained from practicing physicians. Overall attitudes toward house
      calls were positive. Fifty-three percent of the respondents reported making house
      calls, and 8% reported making more than 2 house calls per month. Male physicians,
      those older than 40 years, those in rural settings, and those trained in a
      community-based residency were more likely to make house calls. Patient payer mix
      and practice setting were also related to whether a physician made house calls.
      House calls were most frequently made to geriatric patients, cancer patients,
      trauma patients, and patients with transportation difficulties. Many physicians
      reported using home health agencies for assessment and treatment of patients
      needing home care. CONCLUSIONS: Family physicians agree that house calls are good
      for patients. More than half of the respondents reported that they occasionally
      make house calls. However, few physicians routinely perform house calls.

PMID- 9934387
TI  - Against bottle-feeding.

PMID- 9934388
TI  - Against bottle-feeding.

PMID- 9934389
TI  - Complementary and alternative medicine.

PMID- 9934390
TI  - The International Year of Older Persons: putting aging and research onto the
      political agenda.

PMID- 9934391
TI  - Contributors to and mediators of psychological well-being for informal
      caregivers.
AB  - This article explores the relationships between caregiving stressors and
      caregiver well-being in a representative community sample of disabled elders and
      their informal caregivers. The direct and indirect effects of stressors and
      potential mediators on the outcome of caregiver psychological well-being, as
      measured by depression, were examined using path analysis. Potential mediators of
      the primary stressors on depression included mastery, emotional support; quality
      of relationship between the caregiver and the care recipient, formal service use
      and role overload. Findings indicate that the caregiving stressors (needs for
      care) led to caregiver depression indirectly through their effect on hours of
      care provided and the resulting caregiver perception of role overload. Quality of
      the caregiver/care recipient relationship mediated the relationship of the
      caregiving stressors and caregiver overload and depression. Finally, regardless
      of the level of primary stressors, caregivers with high levels of mastery or
      emotional support were at lower risk of depression. These findings can be used to
      inform the design of proactive caregiver interventions.

PMID- 9934392
TI  - The impact of psychological attributes on changes in disability among low
      functioning older persons.
AB  - We studied the impact of four psychological attributes (neuroticism,
      extraversion, mastery or perceived control, and general self-efficacy
      expectancies) on changes in disability in a community-based sample of 575 low
      functioning elderly persons between 1993 and 1995. Unlike elderly persons with
      low or medium levels of mastery and general self-efficacy expectancies, older
      persons with high levels of such attributes showed no significant increase of
      disability between 1993 and 1995. However, multivariate analyses showed only
      unique contributions of mastery to changes in disability. Neuroticism and
      extraversion were found to be not related to changes in disability, supporting
      previous research outcomes. Findings highlight that, particularly, feelings of
      perceived control are crucial for maintaining functional ability in later life.

PMID- 9934393
TI  - Aging and selective attention: an issue of complexity or multiple mechanisms?
AB  - Previous studies have shown age-associated deficits in selective attention that
      vary as a function of task demands. The present study was conducted to dissociate
      the effect of task complexity on age-related performance differences from
      qualitative differences in cognitive demands. Twenty-four young and 24 older
      adults were administered two versions of the Stroop Test (Hartley, 1993). The
      Color-Block version required identifying the color of a box while ignoring the
      name of a color printed either above or below the box. The Color-Word version
      required naming the color of a word while ignoring the semantic meaning of the
      word (a color name). Each version of the task included a two- and four-color
      choice condition as a manipulation of task complexity. Old and young adults
      performed comparably on the Color-Block Task, but older adults were significantly
      impaired on both conditions of the Color-Word Task, particularly in the four
      choice condition. Results suggest age-related differences in the distinct
      attentional processes demanded by each task are not attributable to general
      slowing.

PMID- 9934394
TI  - Age differences in lapses of intention in the Stroop task.
AB  - The study evaluated the hypothesis that older adults are more susceptible to
      lapses of intention (lapses) than are younger adults, and explored the factors
      contributing to these lapses. The findings of three experiments examining the
      pattern of intrusion errors in the Stroop task revealed that older adults were
      more likely to experience lapses than were younger adults, and that lapses tended
      to be of longer duration in older than younger adults. Lapses were observed under
      conditions of suboptimal controlled attentional processing, when task conditions
      required the allocation of this processing in the service of multiple behavioral
      goals, and during periods of slowed responding. The findings of these experiments
      are consistent with those from a growing number of studies indicating that older
      adults are more susceptible to lapses of intention than younger adults.

PMID- 9934395
TI  - Psychological predictors of mortality in old age.
AB  - Cox regression models examined associations between 17 indicators of
      psychological functioning (intellectual abilities, personality, subjective well
      being, and social relations) and mortality. The sample (N = 516, age range 70-103
      years) comprised participants in the Berlin Aging Study assessed between 1990 and
      1993. By 1996, 50% had died. Eleven indicators were identified as mortality risk
      factors at the zero-order level and six when age was controlled. Low perceptual
      speed and dissatisfaction with aging were uniquely significant after controls for
      age, SES, health, and the 16 other psychological factors. Low intellectual
      functioning was a greater risk for individuals aged 70-84 years than for the
      oldest old (over 85 years). The effects of psychological risk factors did not
      diminish over time. Future research should focus on the mechanisms and time
      frames that underlie the death-relatedness of intellectual functioning and self
      evaluation.

PMID- 9934396
TI  - Content and function of the self-definition in old and very old age.
AB  - Spontaneous self-definition was investigated in a heterogeneous sample of N = 516
      participants of the Berlin Aging Study, aged between 70 and 103 years. The
      content of the self-definition revealed that old and very old persons view
      themselves as active and present-oriented. The self-definition also reflected an
      inward orientation, and central themes of life-review, health, and family.
      Participants generated more positive than negative evaluations in their self
      definition, but the ratio of positive to negative evaluations was less favorable
      for the oldest old (> or = 85 years) than that of persons aged 70 to 84 years.
      Older individuals with more health-related constraints reported fewer and less
      rich self-defining domains (i.e., a less multifaceted self-definition). Positive
      emotional well-being was associated with naming more and richer self-defining
      domains. Multifacetness, however, did not buffer against the negative effect of
      low functional capacity on subjective well-being.

PMID- 9934397
TI  - Financial strain, social relations, and psychological distress among older
      people: a cross-cultural analysis.
AB  - OBJECTIVES: This article examines how financial strain and social relations may
      independently and jointly influence psychological distress among older people in
      four nations. METHODS: Data from four Western Pacific nations (N = 3,277) are
      used to test additive and multiplicative models of the relationships between
      financial strain, social relations, and psychological distress. RESULTS:
      Financial strain is associated with higher levels of psychological distress in
      three of the four nations. Interactive models of the effects of financial strain
      and social relations on distress were uncovered in three of the four nations, but
      the type of social relation influencing the strain-distress relationship varied.
      Subjective-health and IADLs were significant predictors of psychological distress
      in all four nations. DISCUSSION: Findings suggest that although financial strain
      is quite likely to lead to psychological distress among elders, this can be
      mitigated, at least in part, by social relationships. Modernization was not
      associated with higher psychological distress.

PMID- 9934398
TI  - The growth in noncitizen SSI caseloads 1979-1996: aging versus new immigrant
      effects.
AB  - OBJECTIVES: The goal of this research is to assess the degree to which the recent
      growth in the rate of Supplemental Security Income (SSI) usage is concentrated
      among recently arrived elderly immigrants or among earlier arriving immigrants
      who have "aged in place" and thus become eligible for benefits. METHODS: We use
      1980 and 1990 Census data and 1997 Current Population Survey (CPS) data to
      examine whether the growth in the elderly noncitizen caseload during the 1980s
      and 1990s may be attributed to increases in rates of receipt among newly arrived
      elderly immigrants, to increases in rates of receipt among "settled" immigrants
      who have aged into categories that allow them to obtain SSI benefits, or to
      increases in the number of persons in each of these groups. RESULTS: We find that
      the major contribution to the growth in the noncitizen elderly SSI caseload has
      been the significant increase in the rate of receipt among those who have lived
      in the United States for more than 10 years (a smaller increase occurred among
      recent arrivals). This factor accounts for about half of the total growth in the
      caseload and cannot be explained by increases in poverty among noncitizens.
      DISCUSSION: The idea that the availability of SSI for elderly immigrants has
      acted as a magnet for poor elderly immigrants, thereby accounting for the growth
      in the elderly immigrant SSI caseloads during the 1980s and 1990s, does not
      receive much support in the findings of this research.

PMID- 9934399
TI  - Age effects and health appraisal: a meta-analysis.
AB  - OBJECTIVE: The purpose was to clarify the effects of methodological variables in
      the research on age differences in self-rated health and specifically the effects
      of: (a) the item type used to solicit the appraisal, (b) the approach to
      sampling, and (c) the criteria for assembling the age groups for study. METHODS:
      Studies differing on these dimensions were compared using meta-analytic
      techniques. Seventeen usable samples were grouped according to the age
      comparisons--seven compared "young" and "old" samples while ten compared "young
      old" and "old-old" groups. RESULTS: The results failed to support the frequently
      reported health optimism of old-old samples when compared with young-old.
      Further, the findings suggest that the item type used in eliciting the rating of
      health may be instrumental in the respondent's appraisal process. For instance,
      use of the age-comparative item tends to favor "old" groups when compared to
      young, whereas the global health item has an effect in the other direction.
      Effect size was also related to a study's sampling procedure and to the method
      used in assembling groups (i.e., age ranges used to represent young and old).
      DISCUSSION: Practical implications and areas of needed research are discussed.

PMID- 9934400
TI  - Trends in health and ability to work among the older working-age population.
AB  - OBJECTIVES: Because of recent changes in Social Security regulations that will
      soon begin to raise the age of eligibility for full retirement benefits, it is
      important to determine whether health and ability to work at older ages have
      improved in recent years. METHODS: Individual-level data from the National Health
      Interview Survey from 1982 through 1993 are used in this analysis. Trends in self
      reported ability to work, presence of disease, and causes of actual work
      limitation are examined. RESULTS: Men and women in their 60s, that is those in
      the older working ages and younger retirement ages, report significant
      improvement in their ability to work. The change in work ability is large enough
      so the percentage unable to work at age 67 in 1993 is lower than the percentage
      unable to work at age 65 in 1982. This improvement appears to have been similar
      for racial and ethnic groups and across educational subgroups of the population,
      although African Americans and those with lower educational attainment are less
      healthy to begin with. The improvement in health is due to the changing
      educational composition of the population, which is linked to better life-long
      health, different occupational circumstances, and better health behaviors. In
      addition, the improvement in work ability is explained by decline in the
      prevalence of cerebro/cardiovascular diseases and arthritis. DISCUSSION: The
      level of observed improvement in work ability means that the legislated rise in
      age of full eligibility for Social Security benefits should be more than
      compensated for by the improved ability to work.

PMID- 9934401
TI  - Physical activity and its correlates among urban primary care patients aged 55
      years or older.
AB  - OBJECTIVES: Physical inactivity is a leading cause of death and disability, but
      very little is known about physical activity and its determinants among socially
      disadvantaged and medically vulnerable adults. The purpose of this study was to
      assess physical activity and its correlates, including measures of physical
      activity knowledge, perceived barriers, and self-efficacy, among
      socioeconomically disadvantaged older adults. METHODS: A stratified random sample
      of 1,088 patients aged 55 years or older was selected from an urban primary care
      center serving a predominantly low-income population. Of the 1,088 patients
      sampled, 771 (71%) completed an interviewer-administered questionnaire. RESULTS:
      A physical activity instrument, developed specifically for the population being
      studied, showed an average of 65 minutes of physical activity per week. Scores on
      a true-false knowledge quiz were no better than expected by chance, and over two
      thirds reported symptom and perceived environmental barriers to physical
      activity. Lower self-efficacy and greater symptom and motivational barriers were
      found to be associated with less physical activity. DISCUSSION: Given the
      prevalence of inactivity, knowledge deficits, and perceived barriers to physical
      activity, population-specific interventions may be required to improve rates of
      physical activity among socially disadvantaged and medically vulnerable adults.

PMID- 9934402
TI  - Navigation and the mobility of older drivers.
AB  - OBJECTIVES: Age related difficulties in navigating are believed to restrict
      driving mobility. A decline in mobility can have negative implications for
      peoples' well-being and independence. This problem may be more serious than the
      increased risk of collision that occurs with old age. The aim of this research
      was to determine the extent to which age-related difficulties in navigating
      restrict car travel. METHODS: A postal questionnaire survey of 1,186 United
      Kingdom (U.K.) motorists (aged 21 to 85 years) was conducted to determine more
      about people's mobility, the restrictions to their driving, and their driving
      experience. RESULTS: As predicted, respondents were found to report more
      navigation problems with increasing old age. Hierarchical regression analyses
      indicated that navigation problems relate to reduced mobility (miles per week,
      trips per week, and average driving frequency) when controlling for other
      predictors of mobility (age, gender, employment, health, residential location,
      fitness, and ability to afford driving). DISCUSSION: This research highlights the
      need to have better navigational support for drivers, particularly elderly
      drivers. Improved roads signs and in-vehicle navigation aids are two solutions
      that might help enhance the mobility of elderly drivers.

PMID- 9934403
TI  - Official medicine or alternatives medicine.

PMID- 9934404
TI  - Acupuncture in the treatment of asthma: a critical review.
AB  - BACKGROUND: Increasingly, patients are turning to treatments and drugs that are
      considered "alternative" or "complementary" as part of their healthcare. In
      response, the National Institutes of Health (NIH) established an Office of
      Alternative Medicine (OAM) in 1992 to facilitate identification and evaluation of
      alternative and complementary therapies. Acupuncture, a therapy that has been
      used to treat disease in China for approximately 2,500 years has attracted
      considerable attention. NIH in a consensus statement derived from a Fall of 1997
      consensus conference to assess acupuncture has indicated that acupuncture was
      useful in pain control and maybe a useful adjunct treatment for the management of
      asthma. Further, the US Food and Drug Administration has removed acupuncture from
      the "experimental medical devices" category. METHODS: We have extensively
      searched the literature for reports addressing the use of acupuncture in asthma
      treatment. We sought these using the National Library of Medicine, the Office of
      Alternative Medicine's database as well as other databases both English language
      based as well as other languages that catalog literature pertaining to
      alternative and complementary therapies. We then reviewed these reports and
      weighted the validity of the conclusions reached in the reports based on
      assessment of study design, number of subjects studied, duration of studies,
      types and number of controls, and statistical analyses used. RESULTS: Data
      presently in the literature do not provide sufficient support for a useful role
      for acupuncture in asthma management. CONCLUSIONS: Further properly designed
      clinical studies examining the use of acupuncture in asthma are extremely
      important and urgently needed.

PMID- 9934405
TI  - Ipratropium bromide in the recovery phase after methacholine PD20: is there more
      than an antagonist effect?
AB  - Aim of the study was to discover whether the recovery phase after methacholine
      challenge might be influenced by the administration of an antimuscarinic drug and
      to verify the mode and timescale of restored receptor activity. 16 patients with
      severe bronchial hyperreactivity were selected and subjected to methacholine test
      in order to assess: the preventive bronchodilatory effect of ipratropium bromide
      (40 mcg) inhaled before the test and the bronchial spasm spontaneous recovery
      after PD20 at 15, 30 and 60 minutes. Data were subjected to variance and Tukey
      test analysis. The results confirm that ipratropium bromide raises the
      methacholine dose response threshold by a factor of about 10 and also demonstrate
      that the anti-muscarinic drug modified the FEV1 PD20 and influenced the recovery
      phase by intensifying and making the bronchial spasm resolution faster. Thus
      results moreover suggest that the receptor activity restoration depends also on
      the elimination of the muscarinic mediator.

PMID- 9934407
TI  - Erythema multiforme: a review of twenty cases.
AB  - The clinical histories of twenty children hospitalized for erythema multiforme
      (EM) were reviewed. Three forms of the illness were defined according to clinical
      criteria: minor (EMm), intermediate (EMt) and major (EMM). Previous infections
      were associated with the process in 30% of the cases, administration of drugs
      also in 30%, and a combination of the two factors in 30% of the subjects. No
      specific etiology was found in two cases (10%). Respiratory tract symptoms and
      general discomfort preceded the EMM form, and evidence of digestive organ
      involvement was frequent in the EMm form. Erythrocyte sedimentation rate was
      usually high. Postinflammatory sequelae occurred in only two cases, and one
      subject died in the first 24 hours.

PMID- 9934406
TI  - Comparative study between fluticasone propionate and cetirizine in the treatment
      of allergic rhinitis.
AB  - Among the most frequently used drugs in the treatment of allergic rhinitis we
      have to mention topical nasal corticosteroids and H1 antihistamines used both
      systemically and topically. The present study focused the effectiveness and
      tolerability of cetirizine and fluticasone propionate in seasonal allergic
      rhinitis. 54 patients, divided into three homogeneous groups, underwent the
      following different treatments: Group 1: Placebo of fluticasone (2 puff per
      nostril once daily by aerosol) + cetirizine (10 mg/die per os) for 60 days. Group
      2: Fluticasone (100 mg per nostril once daily by aerosol) + placebo of cetirizine
      (per os) for 60 days. Group 3: Cetirizine (10 mg/die per os) for 60 days +
      fluticasone (100 mg per nostril once daily by aerosol) for 20 days. The patients
      reported nasal symptoms (sneezing, obstruction, itching, rhinorrea) on a clinical
      diary. ECP levels in nasal secretions were investigated in all patients to
      determine the anti-inflammatory activity of both treatments. Cetirizine resulted
      very effective in the treatment of sneezing, itching and acqueous rhinorrea
      whereas not much effective on nasal obstruction. On the contrary, fluticasone,
      which acted effectively on nasal obstruction, resulted inefficacious on the other
      symptoms. The third group of patients achieved the best results on all four
      symptoms, including obstruction, which continued even after interrupting the
      treatment with fluticasone. The ECP levels were significantly reduced by both
      treatments. The side effects in all 3 groups were rare and not serious. From
      these results we can assert that the synergic action of the two drugs, achieves
      the best effectiveness, that the fluticasone treatment can be limited to 20 days
      cycles and finally that both molecules are well tolerated.

PMID- 9934408
TI  - Allergic reactions to honey and royal jelly and their relationship with
      sensitization to compositae.
AB  - Honey and royal jelly are complex etherogeneous mixtures of flowers' nectar,
      sugars, proteins and bee's glandular secretions. The existence of a type I
      hypersensitivity to honey is still matter of debate, while an aetiological role
      of Compositae pollens in the clinical manifestations following honey ingestion
      has been envisaged. We describe two cases of severe systemic reactions
      (anaphylaxis and generalized urticaria/angioedema) due to honey and royal jelly
      ingestion in patients sensitized to compositae (mugwort). Both patients had a
      skin and RAST positivity to mugwort and a positive prick-by-prick to the
      offending foods. Moreover, in one of the two patients the RAST-inhibition assay
      showed the strong cross-reactivity between the proteins of honey and mugwort and
      the SDS-PAGE analysis showed that the major proteic bands from honey and mugwort
      extracts are largely superimposable. Both the clinical data and the laboratory
      analysis support the hypothesis of a strict link between sensitization to
      compositae and adverse reactions to honey and jelly.

PMID- 9934409
TI  - Melkersson-Rosenthal syndrome in a diabetic boy.
AB  - The Melkersson-Rosenthal syndrome (MRS) consists of recurrent edema of the lips,
      intermittent facial palsy and furrowed tongue. This is the classic triad which
      defines the syndrome, although it is accepted that the presence of two
      manifestations or one with a granulomatous cheilitis in the biopsy, are
      sufficient to make the diagnosis. The case of a 15 year-old diabetic boy is
      presented. He had a persistent edema of the upper lip of one-year duration, which
      started abruptly without any clear etiologic correlation. He was treated with
      antihistaminics and corticosteroids without improvement but with diabetic
      imbalance. The complementary examinations were normal and the biopsy was
      compatible with granulomatous cheilitis. Despite the low incidence and the fact
      that there is no specific treatment, MRS has to be considered as a diagnostic
      possibility in a patient with recurrent edema although not necessarily having the
      complete triad.

PMID- 9934411
TI  - The effect of anabolic steroids and corticosteroids on healing of muscle
      contusion injury.
AB  - The effect of an anabolic steroid (nandrolone decanoate, 20 mg/kg) and a
      corticosteroid (methylprednisolone acetate, 25 mg/kg) on healing muscle injured
      with a drop-mass technique in a reproducible muscle contusion injury model in the
      rat was studied. Healing was determined by measuring active contractile tension
      in each muscle and histologic analysis. At day 2, the corticosteroid group showed
      significant improvement in both twitch and tetanic strength relative to the
      controls. At day 7, this effect was reversed and the corticosteroid muscles were
      significantly weaker than the control muscles, but there was still no significant
      effect seen in the anabolic steroid group. At day 14, the corticosteroid muscles
      were totally degenerated, with disorganized muscle fiber architecture. The
      anabolic steroid muscles were significantly stronger in twitch, and a similar
      trend was seen in tetanus relative to control muscles. The results indicate that
      in an animal model corticosteroids may be beneficial in the short term, but they
      cause irreversible damage to healing muscle in the long term, including
      disordered fiber structure and a marked diminution in force-generating capacity.
      Anabolic steroids may aid in the healing of muscle contusion injury to speed the
      recovery of force-generating capacity. Although anabolic steroids are considered
      renegade drugs, they may have an ethical clinical application to aid healing in
      severe muscle contusion injury, and their use in the treatment of muscle injuries
      warrants further research.

PMID- 9934410
TI  - Osteoarthritis--a sports medicine problem?

PMID- 9934412
TI  - Evaluation of the anatomy of the common peroneal nerve. Defining nerve-at-risk in
      arthroscopically assisted lateral meniscus repair.
AB  - A two-part study was undertaken to clarify the anatomy of the common peroneal
      nerve at the level of the lateral joint line and risk factors associated with
      arthroscopically assisted inside-out lateral meniscus repair. In part I, 70 legs
      in 35 preserved cadavera were dissected to evaluate the relevant anatomy of the
      common peroneal nerve; 7 (10%) manifested division of the common peroneal nerve
      into deep and superficial branches proximal to the knee joint. A cutaneous branch
      not previously described in the literature emanated from the common peroneal
      trunk in 21 of the legs (30%). In part II, arthroscopically assisted inside-out
      lateral meniscus repair was performed on 10 fresh-frozen cadaveric knees.
      Divergence between suture arms increased as suture position was sequentially
      posterior. Capture of a nerve branch occurred in 2 knees (20%) when posterior
      retraction was not used. Nerve involvement was eliminated when a retractor was
      employed. There was significant anatomic variability in the course and branching
      pattern of the common peroneal nerve at the level of the lateral joint line.
      During arthroscopically assisted inside-out lateral meniscus repair, risk of
      injuring the peroneal nerve was related to suture position because of the
      proximity of anatomic structures and the tendency for suture divergence with soft
      tissue tethering.

PMID- 9934413
TI  - Open meniscal repair: clinical and magnetic resonance imaging findings after
      twelve years.
AB  - The purpose of this study was to document the longterm clinical, radiographic,
      and magnetic resonance imaging results after open meniscal repair. Twenty-two
      patients, with 23 open meniscal repairs, were evaluated after a mean follow-up of
      12.9 years using patient history, physical examination, KT-1000 arthrometer
      testing, the "Orthopaedische Arbeitsgemeinschaft Knie" knee evaluation scheme,
      Tegner activity score, weightbearing radiographs, and magnetic resonance imaging.
      Two of the 22 patients had retears and both occurred in unstable knees.
      Radiographs revealed no degenerative changes in 17 of the 23 compartments. Grade
      III and IV signal alterations were present on magnetic resonance imaging scans in
      more than 50% of the repaired menisci. We concluded that the longterm survival
      rate of repaired menisci was 91%, and that magnetic resonance imaging is
      unsuitable for diagnosis of the healing process of a repaired meniscus.

PMID- 9934414
TI  - Bankart procedure augmented by coracoid transfer for contact athletes with
      traumatic anterior shoulder instability.
AB  - We investigated the clinical efficacy of the Bankart procedure augmented by
      coracoid transfer for traumatic anterior shoulder instability in athletes playing
      contact sports. Eighty-three athletes (85 joints) with traumatic anterior
      shoulder instability who underwent the combined procedure were studied. The mean
      patient age at surgery was 21 years, and the mean follow-up period was 5.8 years
      (range, 2 to 12). According to the Rowe scoring system, the clinical results were
      graded as excellent for 58 shoulders, good for 21, fair for 5, and poor for 1,
      with an average score of 91 points. The overall success rate was 93%. A complete
      return to contact sports was achieved by 73 of the 83 patients (88%). The average
      loss of external rotation was 15 degrees with the arm at the side and 7 degrees
      with the arm in 90 degrees of abduction. The complications were nonunions in two
      cases, screw breakage in one case, and axillary nerve injury in one. This
      procedure can achieve a good clinical outcome for contact athletes with traumatic
      anterior shoulder instability.

PMID- 9934415
TI  - Mechanical tensile properties of the quadriceps tendon and patellar ligament in
      young adults.
AB  - We analyzed mechanical tensile properties of 16 10-mm wide, full-thickness
      central parts of quadriceps tendons and patellar ligaments from paired knees of
      eight male donors (mean age, 24.9 years). Uniaxial tensile testing was performed
      in a servohydraulic materials testing machine at an extension rate of 1 mm/sec.
      Sixteen specimens were tested unconditioned and 16 specimens were tested after
      cyclic preconditioning (200 cycles between 50 N and 800 N at 0.5 Hz). Mean cross
      sectional areas measured 64.6 +/- 8.4 mm2 for seven unconditioned and 61.9 +/-
      9.0 mm2 for eight preconditioned quadriceps tendons and were significantly larger
      than those values of seven unconditioned and seven preconditioned patellar
      ligaments (36.8 +/- 5.7 mm2 and 34.5 +/- 4.4 mm2, respectively). Mean ultimate
      tensile stress values of unconditioned patellar ligaments were significantly
      larger than those values of unconditioned quadriceps tendons: 53.4 +/- 7.2 N/mm2
      and 33.6 +/- 8.1 N/mm2, respectively. Strain at failure was 14.4% +/- 3.3% for
      preconditioned patellar ligaments and 11.2% +/- 2.2% for preconditioned
      quadriceps tendons (P = 0.0428). Preconditioned patellar ligaments exhibited
      significantly higher elastic modulus than preconditioned quadriceps tendons.
      Based on mechanical tensile properties analyses, the quadriceps tendon-bone
      construct may represent a versatile alternative graft in primary and revision
      anterior and posterior cruciate ligament reconstruction.

PMID- 9934416
TI  - Structural properties of six tibial fixation methods for anterior cruciate
      ligament soft tissue grafts.
AB  - This study compared the stiffness (K), yield load (YL), and slippage (SL) of six
      tibial fixation methods. These properties were determined from load-to-failure
      and cyclic tests of double-looped tendon grafts fixed to both animal and young
      human tissue. Tandem washers (K = 259 N/mm, YL = 1159 N, SL = 0.5 mm) and the
      Washerloc (K = 248 N/mm, YL = 905 N, SL = 2.0 mm) were the two best fixations. At
      500 N of load, which is the estimated daily tension of an anterior cruciate
      ligament graft during intensive rehabilitation, slippage was significantly
      greater in either of the other two methods for sutures tied to a post (4.9 mm),
      double staples (3.3 mm), and a 20-mm spiked metal washer (3.5 mm). Interference
      screw fixation performed well in animal tissue (YL = 776 N), but was
      significantly worse in young human tissue (YL = 350 N), with 57% of the fixations
      failing before 500 N of load. Animal tissue should not be used to estimate the
      performance of interference screw fixation in human tissue. Because 57% of the
      interference screw fixations using human tissue failed at loads below 500 N,
      their ability to provide adequate fixation during intensive rehabilitation should
      be questioned. However, both the Washerloc and tandem washers and screws provide
      fixation structural properties in young human tibia that should be appropriate
      for intensive rehabilitation.

PMID- 9934418
TI  - Isolation of the vastus medialis oblique muscle during exercise.
AB  - The purpose of this study was to selectively challenge the vastus medialis
      oblique muscle in comparison with the vastus lateralis, the vastus intermedius,
      and the vastus medialis longus muscles by performing nine sets of strengthening
      exercises. These knee rehabilitation exercise included isometric knee extension
      with the hip at neutral, 30 degrees external, and 30 degrees internal rotation;
      isokinetic knee extension through full range; isokinetic knee extension in the
      terminal 30 degrees arc; sidelying ipsilateral and contralateral full knee
      extension; and stand and jump from full squat. Electrical activity of the vastus
      medialis oblique, the vastus lateralis, the vastus intermedius, and the vastus
      medialis longus muscles was measured in eight uninjured subjects. Our study
      showed that isometric exercises in neutral and external rotation of the hip will
      challenge both the vastus medialis oblique and the vastus lateralis muscles. The
      results suggest that the electromyographic activity of the vastus medialis
      oblique muscle was not significantly greater than that of the vastus lateralis,
      the vastus intermedius, and the vastus medialis longus muscles during the nine
      sets of exercises. Results suggest that the vastus medialis oblique muscle cannot
      be significantly isolated during these exercises.

PMID- 9934417
TI  - Isolated arthroscopic meniscal repair: a long-term outcome study (more than 10
      years).
AB  - A single surgeon's consecutive series of 50 arthroscopically repaired meniscal
      tears in 48 patients was retrospectively reviewed. None of these patients had
      concomitant ligament damage to the knee. The average follow-up period was 10
      years, 9 months. Criteria for clinical success included 1) history of pain of
      grade 1 or less and absence of locking, catching, or giving way; 2) a physical
      examination demonstrating no significant effusion and a painless and negative
      jump sign; and 3) no subsequent surgical procedures on the repaired meniscus.
      Patient satisfaction was quite high, although clinical confirmation was possible
      in only 38 knees, indicating a clinical success rate of 76%. Bilateral standing
      radiographs were obtained on these 38 operated knees and were evaluated using
      Fairbank's classification. Evaluation of the radiographs revealed that 8% of the
      operated knees had minimal joint changes, as compared with 3% in the
      contralateral, nonoperated knee. This study demonstrates that arthroscopic
      meniscal repair in knees with isolated meniscal tears has the potential for a
      long-term successful clinical and radiographic outcome.

PMID- 9934419
TI  - Effects of therapeutic ultrasound on the regeneration of skeletal myofibers after
      experimental muscle injury.
AB  - Therapeutic ultrasound is used by many in the treatment of muscle injuries, but
      no previous attempts to objectively assess its effects on regenerating skeletal
      myofibers have been published. In this descriptive study, we followed the
      regeneration of contusion injury to the rat gastrocnemius muscle during treatment
      with pulsed ultrasound. The speed of myoregeneration in ultrasound-treated
      animals was compared with that in control animals by immunohistochemical,
      morphometric, and scintigraphic analyses. Although satellite cell proliferation
      was enhanced significantly (up to 96%) by the ultrasound treatment during the
      early stages of regeneration, there was no such effect on myotube production. The
      period of rapid fibroblast proliferation was extended from 3 to 4 days in the
      control group to 7 to 10 days in the ultrasound therapy groups, whereas
      recapillarization was virtually unaffected. We conclude that although treatment
      with pulsed ultrasound can promote the satellite cell proliferation phase of the
      myoregeneration, it does not seem to have significant effects on the overall
      morphological manifestations of muscle regeneration.

PMID- 9934420
TI  - Tennis after total hip arthroplasty.
AB  - The purpose of this study was to characterize patients who play tennis after
      undergoing hip arthroplasty in terms of their functional abilities and degree of
      satisfaction. A questionnaire was sent to all United States Tennis Association
      member associations in a tri-state area to identify players who had undergone a
      hip arthroplasty. The study group had 50 men and 8 women with a mean age of 70
      years (range, 47 to 89). Only 14% of the patients' surgeons approved this tennis
      activity, with 34% of the surgeons recommending only doubles. Three patients
      required revision surgery after a mean of 8 years. One year after arthroplasty,
      players played both singles and doubles approximately three times per week. All
      tennis players were extremely satisfied with their hip arthroplasties and their
      increased ability to participate in their favorite sport. Because this study was
      confined to association members, further studies are needed to assess the general
      effect of tennis on total hip arthroplasty. Until future studies are performed,
      the authors would recommend that physicians advise caution in tennis activities
      and to carefully follow their patients yearly to see if osteolysis is occurring
      prematurely.

PMID- 9934421
TI  - Which is more useful, the "full can test" or the "empty can test," in detecting
      the torn supraspinatus tendon?
AB  - The purpose of this study was to determine the clinical usefulness of the full
      can and empty can tests for determining the presence of a torn supraspinatus
      tendon. The two tests were performed in 143 shoulders of 136 consecutive
      patients. In each test, the muscle strength was determined by manual muscle
      testing, and the presence of pain during the maneuver was recorded. We
      interpreted the tests as positive when there was 1) pain, 2) muscle weakness, or
      3) pain or muscle weakness or both. Shoulders were examined by high-resolution
      magnetic resonance imaging with 95% accuracy for full-thickness rotator cuff
      tears. There were 35 shoulders with full-thickness tears of the supraspinatus
      tendon. The accuracy of the tests was the greatest when muscle weakness was
      interpreted as indicating a torn supraspinatus tendon in both the full can test
      (75% accurate) and the empty can test (70% accurate). However, there was no
      significant difference between the accuracy of the tests when this criterion was
      used. Pain was observed in 62 shoulders (43%) during the full can test and in 71
      shoulders (50%) during the empty can test, but the difference was not
      statistically significant. Muscle weakness should be interpreted as indicative of
      supraspinatus tendon tear. Using this indicator, both tests are equivalent in
      terms of accuracy, but considering pain provocation, the full can test may be
      more beneficial in the clinical setting.

PMID- 9934422
TI  - Neuromuscular properties and functional aspects of taped ankles.
AB  - We used electromyographic and goniometric methods to test 40 subjects to describe
      the neuromuscular and biomechanical adaptation of the ankle with respect to
      application of two different adhesive tapes and to exercises. The neuromuscular
      responses to inversion injury simulation, together with the mechanical
      displacements of the joint complex, were analyzed before and after controlled
      athletic exercises. The proprioceptive amplification ratio was calculated on the
      basis of the integrated reflex electromyographic results and on the maximum
      inversion amplitude. Relevant stability gains were achieved immediately after
      applying tape. There was reduced tape stability after athletic exercise for one
      of the two tape materials tested. No further loosening was detected, even after
      prolonged wearing of tape (24 hours). Compared with the unprotected ankle, the
      taped ankle had a significant increase in the proprioceptive amplification ratio.
      Both fatigue and mechanical loosening may be responsible for the significant
      reduction in this ratio immediately after exercise. After the 24-hour interval,
      the ratio was increased, which could be explained by physiologic neuromuscular
      regeneration and mechanical restabilization of the tape itself. The sensitivity
      of the proprioceptive amplification ratio, both to external stabilization and to
      internal fatigue, supports its potential value to quantify functional joint
      stability.

PMID- 9934423
TI  - The effect of knee bracing after anterior cruciate ligament reconstruction. A
      prospective, randomized study with two years' follow-up.
AB  - The purpose of this prospective, randomized, clinical trial was to evaluate the
      effect of knee bracing after anterior cruciate ligament reconstruction. Sixty
      patients were randomized into one of two groups: Patients in the braced group
      wore rehabilitative braces for 2 weeks, followed by functional braces for 10
      weeks, and patients in the nonbraced group did not wear braces. Data were
      recorded preoperatively, and postoperatively after 6 weeks, 3 and 6 months, and 1
      and 2 years. The following outcome measures were used: KT-1000 arthrometry, the
      Cincinnati knee score, goniometry to record range of motion, computed tomography
      to determine thigh atrophy, Cybex 6000 isokinetic testing to evaluate muscle
      strength, three functional knee tests, and a visual analog scale to evaluate
      pain. At all follow-up times there were no significant differences between the
      two groups with regard to knee joint laxity, range of motion, muscle strength,
      functional knee tests, or pain. However, the Cincinnati knee score showed that
      patients in the braced group had significantly improved knee function compared
      with patients in the nonbraced group at the 3-month follow-up, even though the
      braced group showed significantly increased thigh atrophy compared with the
      nonbraced group at 3 months.

PMID- 9934424
TI  - The effect of exercise and rehabilitation on anterior-posterior knee
      displacements after anterior cruciate ligament autograft reconstruction.
AB  - We studied the effect of rehabilitation strength training and return to
      activities on anterior-posterior knee displacements after patellar tendon
      autogenous anterior cruciate ligament reconstruction. A total of 938 measurements
      were sequentially collected for 142 patients with the KT-2000 arthrometer.
      Rehabilitation included immediate knee motion and early weightbearing, light
      sports at 6 months, and competitive sports at 8 months or later. At a minimum of
      2 years after surgery, 121 patients (85%) had normal displacements (less than 3
      mm of increase at 134 N), 14 (10%) had 3 to 5.5 mm of increase (partial
      function), and 7 (5%) had more than 5.5 mm of increase (failed). There was no
      association found between the initial onset of the abnormal displacements in the
      21 knees and either the amount of time after surgery or the rehabilitation
      program. Six of the seven grafts that failed did so in the 1st postoperative
      year. Serial displacement measurements allow early detection of graft stretching
      and subsequent modification of rehabilitation or delay in return to strenuous
      activities. These measurements showed that the rehabilitation program used in
      this study was not itself injurious and resulted in an acceptable failure rate of
      5%.

PMID- 9934425
TI  - Injury risk in first-time snowboarders versus first-time skiers.
AB  - Between 1994 and 1996 we studied injury patterns in more than 22,000 first-time
      snowboarders and first-time skiers to determine the comparative injury risk of
      these two popular sports coexisting in winter resort areas. The first-time
      participants included in this study had no previous experience in their activity
      of choice and enrolled in Learn to Snowboard and Learn to Ski programs in two
      major northeastern ski resorts. Data were gathered from physician evaluations at
      the medical clinics at each mountain. Two hundred seventy-three (4%) of the first
      time snowboarders (N = 6585), and 641 (4%) of the first-time skiers (N = 15,795)
      sustained an injury. Injuries were further evaluated by location (upper
      extremity, lower extremity, head, and trunk area) and severity (emergent versus
      nonemergent). Snowboarders had a higher percentage of upper extremity injuries
      (53%), while skiers had a higher percentage of lower extremity injuries (63%).
      Snowboarders, however, sustained a significantly higher incidence of emergent
      injuries (such as fracture, concussion, dislocation, lost teeth) necessitating
      immediate intervention. While there have been other reports describing injuries
      in these activities, no previous study attempted to look at the first-time
      participants with similar age, experience, and equipment to determine comparative
      risk. We conclude that for the first-time participant, snowboarding does show a
      higher incidence of emergent injuries.

PMID- 9934427
TI  - Failure of a biodegradable meniscal arrow. A case report.

PMID- 9934426
TI  - Magnetic resonance imaging appearance of teres major tendon injury in a baseball
      pitcher.

PMID- 9934428
TI  - Isolated fracture of the vertebral articular facet in a gymnast. A spondylolysis
      mimic.

PMID- 9934429
TI  - Cardiovascular disease in athletes.
AB  - As a physician, coach, or trainer, we see athletes as healthy, physically fit,
      and able to tolerate extremes of physical endurance. It seems improbable that
      such athletes may have, on occasion, underlying life-threatening cardiovascular
      abnormalities. Regular physical activity promulgates cardiovascular fitness and
      lowers the risk of cardiac disease. However, under intense physical exertion and
      with a substrate of significant cardiac disease--whether congenital or acquired-
      athletes may succumb to sudden cardiac death. The deaths of high-profile athletes
      receive much attention through the national news media, but there are also deaths
      of other athletes. With repetitive, intense physical exercise, the heart
      undergoes functional and morphologic changes. Knowledge of those changes may help
      one identify cardiovascular abnormalities that can cause sudden death from the
      heart known as an "athlete's heart." This article will review cardiovascular
      diseases that may limit an athlete's participation in sports and that may put an
      athlete at risk for sudden cardiac death. It also reviews the extent and
      limitations of the cardiovascular preparticipation screening examination. Team
      physicians, coaches, and trainers must understand the process of evaluation of a
      symptomatic athlete that may indicate significant cardiac abnormalities. Finally,
      guidelines to determine eligibility of athletes with cardiovascular disease to
      return to sports will be reviewed.

PMID- 9934430
TI  - Open capsulorrhaphy with suture anchors for recurrent anterior dislocation of the
      shoulder.

PMID- 9934431
TI  - Effects of locus coeruleus stimulation on the responses of SI neurons of the rat
      to controlled natural and electrical stimulation of the skin.
AB  - 1. The effects of microstimulation of the locus coeruleus (LC) region on the
      spontaneous discharge and the response of SI neurons to natural and electrical
      stimulation of the skin have been investigated in 26 urethane anesthetized
      Sprague-Dawley rats. In particular, one or two air puffs, 5-10 msec in duration,
      1-2 psi, usually separated by an interval of 40 msec, were applied on the hairy
      skin of the wrist or the forepaw at the presentation rate of 1/sec. For units
      unresponsive to air puffs, similar presentation of low intensity electrical
      stimuli (0.2-5.0 V, 0.2-0.4 msec pulses) were applied through two needles
      inserted on the most effective area of the skin. Both natural and electrical
      stimulations of the skin were applied under control conditions, as well as 50
      msec after a 250 msec train of 0.3 msec pulses at 40 Hz. 20-30 microA applied
      stereotaxically to the LC complex through a tungsten microelectrode. 2. Not all
      cortical units exhibited spontaneous discharge. Most of the units, however, which
      were spontaneously active, were inhibited by electrical stimulation of the LC
      complex, while the remaining ones were excited. The sites of stimulation, which
      included either the LC proper or the locus subcoeruleus, were identified
      following both anatomical and physiological criteria. 3. SI neurons recorded at
      sites between 400 and 950 microns below the surface of the cortex, thus being
      most likely granule cells of layers III and IV, responded to cutaneous stimuli
      with spikes which occurred with a latency of 20-30 msec in response to single air
      puffs and a latency of 15-20 msec in response to single electrical pulses to the
      skin. In both instances the response to the second stimulus applied at the
      interstimulus interval of 40 msec was markedly reduced or abolished due to
      postexcitatory inhibition following the response to the first stimulus (in-field
      inhibition). In contrast, units particularly located at or below 1000 microns
      from the cortical surface, which were of very large size probably corresponding
      to large layer V pyramidal cells, were often difficult to activate with air puffs
      applied at the centre of the receptive field (RF) and were submitted to
      electrical stimulation of the skin. 4. Among the 59 isolated SI units tested
      either to air puffs (45 neurons) or to electrical skin stimulation (14 neurons),
      15 units (i.e., 25.4%) were facilitated, while 12 units (i.e., 20.3%) were
      inhibited following stimulation of the LC complex. 5. A marked feature of the
      facilitatory effects which usually involved the predominant response to the first
      air puff, but also the smaller response to the second puff, was that the increase
      in the number of spikes per stimulus was accompanied by a temporal focusing of
      the responses characterized by a clear tightening of the latency and narrowing of
      the peak of activity, which was often accompanied by some level of tonic
      inhibition of the background discharge. Thus, LC stimulation increased the signal
      to-noise ratio of SI neuronal responses to skin stimulation. When inhibitory
      effects were induced by LC stimulation, they clearly affected the unit response
      to the first air puff, which was severely depressed. However, the response to the
      second puff could be facilitated, suggesting that LC stimulation might have
      produced inhibition of those inhibitory interneurons responsible for the
      postexcitatory inhibition of the units under examination. Evidence for spatial
      focusing of the response was not easily documented. In some units, however, LC
      stimulation produced either facilitation of the responses to puffs at the
      receptive field center and inhibition of the responses to puffs at the edge at
      the receptive field or vice versa. 6. Since the LC complex contains in the rat a
      predominant population of noradrenergic neurons, it is likely that the effects
      described above were mainly due to activation of these noradrenergic neurons. 7.
      (ABSTRACT TRUNCATED)

PMID- 9934432
TI  - Epileptic discharge of cortical, subcortical and spinal neurons in penicillin
      induced experimental epilepsy.
AB  - The sensitivity and electrophysiological patterns of paroxysmal activity induced
      in different brain structures by topical application of penicillin-G were
      evaluated in the rat. Recordings were carried out in five groups of animals, in
      telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The
      following analysis were carried out: frequency distribution histograms, latency
      and time course duration of paroxysmal activity, duration and amplitude of
      epileptic bursts. The results obtained showed that the nervous structures tested
      with penicillin-G had a different epileptogenic sensitivity and response pattern
      which significantly changed along the cerebral cortex-spinal cord axis. The
      highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500
      600 microns depth; in the other cortical layers, a significant lenghtening in
      latency was observed. Among the other structures, the spinal cord seemed to be
      the most sensitive target to the epileptogenic action of penicillin-G, whereas in
      the remaining structures, sensitivity significantly decreased in rostro-caudal
      direction. As far as the features of the paroxysmal activity are concerned,
      significant differences among tested structures were observed. In particular,
      within the SI cortex, the main differences were represented by the gradual
      increase in burst frequency and voltage from the surface to the IVth layer and by
      their subsequent decrease in deeper layers (V-VI). In the diencephalon, the
      paroxysmal activity was similar to that observed in more superficial and deeper
      cortical layers even though epileptic bursts showed a lower amplitude.
      Mesencephalon and rombencephalon displayed a paroxysmal activity with a
      distinctive feature, characterized by long lasting bursts of low amplitude,
      although bulbar outbursts showed a shorter duration than the mesencephalic ones.
      In the spinal cord, the epileptiform activity displayed a different paroxysmal
      pattern, characterized by the longest duration and the highest amplitude. The
      different sensitivities of the investigated brain structures to penicillin-G and
      the characteristics of the induced paroxysmal activity have been extensively
      discussed.

PMID- 9934433
TI  - Pyramidal control of heart rate and arterial pressure in cats.
AB  - The pyramidal control of the heart rate (HR) and the arterial pressure (AP) was
      investigated in the cat. Experiments were conducted in order to determine
      relative contribution of vagal and sympathetic components to this control. In
      eighteen anesthetized and curarized cats, electrical stimulations were applied to
      the pyramidal tract (PT), followed by pharmacological blockade of the sympathetic
      cardiac control or by bivagotomy. HR and mean arterial pressure (MAP) were
      recorded in response to pyramidal stimulations before and after bulbar
      transections sparing only the PT, beta 1-blockade by atenolol administration
      and/or bilateral vagotomy. Results showed that the stimulation of the PT elicits
      significant cardiac accelerations and MAP increases in all animals. Furthermore,
      bulbar transections allowed to conclude that pyramidal influences acted at bulbar
      level and not on spinal cardiovascular neurons. After beta 1-blockade by
      atenolol, HR increases were reduced by about 70% and those of MAP by about 30%;
      after bilateral vagotomy, cardioaccelerations were reduced by about 30% but no
      significant reductions of MAP were observed; finally, beta 1-blockade combined
      with vagal section suppressed cardioaccelerations and significantly reduced the
      MAP increases. These results suggest the existence of a direct cortical control,
      via the pyramidal tract, to cardiovascular centers of the medulla, probably
      mediated by pyramidal collaterals. This control appears to be organized following
      a reciprocal autonomic pattern where the suppression of the vagal inhibition is
      associated with a concomitant sympathetic excitation. The present work also
      provides data in favour of a central command coupling somatic programs and
      cardiac adjustments during motor acts.

PMID- 9934434
TI  - Trigeminal integration of vestibular and forelimb nerve inputs.
AB  - Experiments were carried out on anaesthetized guinea pigs to evaluate whether
      vestibular and somatosensory informations converge upon the same trigeminal
      motoneurones and, if so, how they interact in the modulation of their activity.
      It was found that excitatory responses occurred in these motoneurones when an
      appropriate electrical stimulation was applied to the common radial nerve. The
      same was true if the electrical stimulus was applied to the vestibular ampullae.
      In another set of experiments the stimulation was applied both to the vestibular
      ampullae and to the common radial nerve at various time-intervals. The amplitude
      of the motoneuronal responses to common radial nerve stimulation was reduced when
      preceded by a vestibular stimulation. The same was true when the sequence of
      stimulations was reversed: in this case there was a decrease in amplitude of the
      testing response to vestibular stimulation. The degree of these reductions
      depended upon the time-interval elapsed between the afferent stimulations. The
      maximal degree of depression was observed at 4-6 ms time-interval for
      conditioning vestibular stimulation and at 10-12 ms time-interval for
      conditioning radial nerve stimulation. It appears, therefore, that somatosensory
      and vestibular signals may modulate the activity of trigeminal motor units
      innervating masticatory muscles, suggesting that extratrigeminal afferents may
      control the contraction of these muscles.

PMID- 9934435
TI  - Histochemical analysis of fiber composition of skeletal muscles in pigeons and
      chickens.
AB  - The fiber type composition of 12 skeletal muscles in pigeon and chicken were
      studied by staining for myofibrillar adenosine triphosphatase (ATPase: pH 10.3)
      and succinate dehydrogenase (SDH). The muscles contained three types of muscle
      fibers: FG (fast-twitch glycolytic), FOG (fast-twitch oxidative glycolytic), and
      SO (slow-twitch oxidative). The numbers and diameters of the different types of
      fibers were examined. The muscles of chickens and pigeons consisted mainly of FG
      and FG + FOG fibers, respectively. In m. pectorals superficialis (PS) and m.
      latissimus dorsi (LD), which produce flapping movements in pigeons, some clusters
      of FG fibers were observed among FOG fibers and the diameter of FG fibers was
      more than twice as large as that of FOG fibers.

PMID- 9934436
TI  - [Space biomedicine in the sciences system and in the life of human society].
AB  - The paper deals with the milestones of the space biomedicine advancement, its
      integration in the system of sciences and the life of humanity, and the role of
      Oleg G. Gazenko in its evolution.

PMID- 9934437
TI  - [Decompression sickness-one of the vital problems of aerospace medicine].
AB  - The author reviews the literature on decompression sickness (DCS) constituting
      one of the major problems of aerospace medicine. He speculates on the terms
      describing this health condition and offers the retrospective of hypothesised
      causes for DCS development. The paper outlines main DCS symptoms and reports
      statistics on the DCS incidence rate in flying personnel when piloting aircraft
      and training in altitude chambers, and in volunteered test-subjects during
      physiological experiments with simulated ascents in order to mimic the
      extravehicular activities of cosmonauts and to test the altitude gear. Underlined
      is the value of publications by many Russian and foreign investigators who
      contributed significantly to development of the scientific and applied aspects of
      this problem. The currently available and theoretically possible countermeasures
      against DCS in cosmonauts during EVA are considered.

PMID- 9934438
TI  - [Mechanisms of homeostasis establishment during prolonged microgravity].
AB  - Investigations performed during prolonged microgravity were aimed at
      determination of phenomenology of the microgravity effects, and collection of
      data that would permit analysis of the micro-g specific homeostasis. As was
      stated, long-term microgravity alters the level of functioning of the main body
      systems, and a number of parameters of human metabolism and internal medium. It
      also instigates restructuring of some tissues and organs (primarily the
      musculoskeletal apparatus), brings along another level of energy and plastic
      (protein) metabolism, enhances the catabolic processes, and modifies the
      neuroendocrine regulation. In microgravity, the balance of functional loads on
      various body systems changes affecting rearrangement of the homeostasis
      regulation. The paper details the functional and morphological changes arising
      during long stay in microgravity and mechanisms culminating in a novel
      homeostasis in microgravity.

PMID- 9934439
TI  - [Hybrid biophysical-chemical life support systems for human].
AB  - Based on comparison of biological and physical/chemical regenerative life support
      systems (LSS) the authors maintain that hybrid LSS will apparently be the most
      congruous for future space vehicles. In their opinion, a hybrid LSS will evolve
      from a basic LSS with maximum regenerative functions. One of the precursory
      experimentally tested LSS could serve as the basic model. This basic LSS may and
      must incorporate physical/chemical technologies which, without affecting the
      chemical nature of substances within the system, will subserve synchronization of
      synthesis and destruction processes underlying the turnover in any ecosystem.
      Therein lies the advantage of hybrid LSS over modelling of natural ecosystems in
      which physical and chemical cycles of substance transformation take much longer
      time than the biological ones.

PMID- 9934440
TI  - [Human tolerance of +Gx loads in anti-G suits during deorbiting of the "Soiuz"
      space vehicles].
AB  - Reported are results of the study of tolerance of the "thorax-back" g-loads (+Gx)
      during deorbiting of 83 total suited and unsuited cosmonauts in the period of
      1997-1997. G-loads averaged 3.7 +/- 0.058 units (from 3.1 up to 5.1 units).
      Pneumatic gradient G-suits (PGS) Karkas and Centaur had a positive effect on the
      +Gx tolerance of humans following microgravity. As compared with unsuited crews
      returning from missions of similar duration, wearing PGS has proven to improve
      the general health of cosmonauts and to reduce the strain of the leg and
      abdominal muscles. Tight fitting of PGS abolished visual disorders due to the
      longitudinal component of G-loads that were registered in 6.6% of observations of
      unsuited cosmonauts. Sinus tachycardia was significantly weaker (P < 0.05). The
      authors recommend the use of the standard antiblackout Centaur suit as the
      efficacy of this PGS was equal to that of Karkas while its ergonomic
      characteristics were superior.

PMID- 9934441
TI  - [Prevention of respiratory muscles deconditioning and deterioration of aerobic
      working capacity in prolonged weightlessness and hypokinesia].
AB  - According to the previous study [2], simulation of the physiological effects of
      weightlessness leads to deconditioning of the respiratory muscles which, in its
      turn, may be a factor impacting the aerobic working capacity. In the present work
      the experimental findings laid the basis for a physiological concept for
      medical/engineering requirements to countermeasures against deconditioning of the
      respiratory muscles, designing and laboratory and physiological testing of a
      prototype of training loading vest Elastik-R. The vest was shown to enhance speed
      and force qualities of the respiratory muscles in training athletes, to improve
      ventilation and gas-exchange functions of the lung, and to increase physical
      performance and aerobic capacity. Recommendations on utilization of the Elastik-R
      vest during space flight have been issued.

PMID- 9934443
TI  - [Ethic aspects of conducting physiological-hygienic and psychological studies on
      human subjects as applied to the activities in extreme environments].
AB  - The paper deals with ethic concerns of biomedical research involving human
      subjects aimed at mitigating risks for and raising the effectiveness of humans in
      extreme environments. Cited are the main principles of the Nuremberg Code,
      Helsinki Declaration, Convention of the European Council on Bioethics and other
      international and national documents regulating ethic implementation of research
      with participation of human subjects. The 6-year experience of the Bioethics
      Commission convened at SRC RF--IBMP is summarised.

PMID- 9934442
TI  - [Comparative analysis of changes in rats organisms exposed to microgravity and
      head-down suspension].
AB  - Comparative analysis of metabolic and structural shifts in rats following 14 days
      of microgravity aboard biosatellite Cosmos-2044 and their tail-suspended
      synchronous controls gave evidence that suspension-induced deprivation of hind
      limbs of support loading yields inherent to microgravity shifts the endocrine
      control of energy, plastic, and mineral metabolism. The conclusion has been drawn
      that tail-suspension can be used as a model of the microgravity effects on the
      musculoskeletal apparatus and the endocrine systems controlling metabolism in
      muscles and bones.

PMID- 9934445
TI  - [Military Medical Academy and aerospace medicine (on the bicentennial of the
      Military Medical Academy and the 40th anniversary of the Aerospace Medicine
      Department)].

PMID- 9934444
TI  - [Contribution of O.G. Gazenko to the aviation medicine].

PMID- 9934446
TI  - [The XIth conference on space biology and aerospace medicine (Moscow, Russia,
      June 22-26, 1998)].

PMID- 9934447
TI  - [Role of the Institute of Biomedical Problems in the international cooperation in
      space biology and medicine].

PMID- 9934448
TI  - Coprophilin: an anticoccidial agent produced by a dung inhabiting fungus.
AB  - Coprophilin, a decalin pentanedienoic acid methyl ester, was isolated from an
      unidentified fungus by bioassay guided separation. It inhibited (MIC = 1.5
      microM) the growth of Eimeria tenella in an in vitro assay. The isolation,
      structure elucidation, absolute stereochemistry and biology are described.

PMID- 9934449
TI  - Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors.
AB  - The synthesis and activity of a series of 4,5-diarylimidazole analogs are
      described. One analog had an IC50 of 80 nM, was 6750-selective against COX-1, and
      demonstrated in vivo potency in the mouse air pouch model.

PMID- 9934450
TI  - 4,4,14 alpha-trimethyl 9 beta,19-cyclo-5 alpha-26-homocholesta-24,26-dien-3 beta
      ol: a potent mechanism-based inactivator of delta 24(25)- to delta 25(27)-sterol
      methyl transferase.
AB  - The title compound (4A) was synthesized and tested as a mechanism-based
      inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca
      wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time
      dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact
      value of 0.30 min-1.

PMID- 9934451
TI  - Synthesis of photoaffinity label analogues of alpha-tocopherol.
AB  - Photoaffinity analogues of alpha-tocopherol have been synthesized that
      incorporate the photosensitive 4-azido-2,3,5,6-tetrafluorobenzyloxy group at the
      terminus of unbranched analogues of the naturally occurring phytyl side chain. An
      intermediate from these syntheses has also been used to generate a supported
      ligand for bioaffinity chromatography of alpha-tocopherol binding proteins.

PMID- 9934452
TI  - Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor.
AB  - Aromatic analogs of arcaine were shown to have inhibitory effects on the binding
      of the channel blocking drug [3H]MK-801 to the NMDA receptor complex. The most
      potent compound of the series was an N,N'-bis(propyl)guanidinium which inhibited
      [3H]MK-801 binding with an IC50 of 0.58 microM and an IC50 of 12.17 microM upon
      addition of 100 microM spermidine. The increase in IC50 upon addition of
      spermidine suggests competitive antagonism between the inhibitor and spermidine
      at the arcaine-sensitive polyamine site of the NMDA receptor complex.

PMID- 9934453
TI  - An improved route to 1,2-dideoxy-beta-1-phenyl-D-ribofuranose.
AB  - An efficient synthesis of the aryl nucleoside analogue 1,2-dideoxy-beta-1-phenyl
      D-ribofuranose (1) is described. This route utilizes the addition of
      phenyllithium to a protected 2-deoxyribonolactone followed by reduction with
      triethylsilane/boron trifluoride etherate to selectively produce the beta-anomer.
      Deprotection yields the desired aryl C-nucleoside in 27% overall yield from 2
      deoxy-D-ribose.

PMID- 9934454
TI  - Dual antagonists of platelet activating factor and histamine. 3. Synthesis,
      biological activity and conformational implications of substituted N-acyl-bis
      arylcycloheptapiperazines.
AB  - A series of N-acyl-4-(5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11
      ylidene)piperazines is described that are dual antagonists of PAF and histamine.
      The structural requirements for activity in this series parallel those of their
      previously reported piperidinylidene counterparts. Whereas their global minimum
      energy conformations are different for both series of compounds, computer
      assisted molecular modeling suggests that a common bioactive conformation is
      possible.

PMID- 9934455
TI  - Anti-HIV coumarins from Calophyllum seed oil.
AB  - The seeds of Calophyllum cerasiferum Vesque (Family-Clusiaceae), and Calophyllum
      inophyllum Linn. (Family-Clusiaceae) contain several known coumarins, among which
      were the potent HIV reverse transcriptase inhibitors costatolide and inophyllum
      P. Calophyllum cerasiferum contained (-)-calanolide B as its major coumarin
      constituent in significant amount and thus constitute a renewable source of this
      compound.

PMID- 9934456
TI  - Novel cytotoxic diterpenes from the stem of Dysoxylum kuskusense.
AB  - Three novel diterpenes, dysokusones A (1), B (2), and C (3), were isolated from
      the stem of Dysoxylum kuskusense as cytotoxic substances. The structures were
      established by spectroscopic examinations. Compounds 1, 2, and 3 were cytotoxic
      toward HL-60(TB) cells with EC50 values of 2.25, 6.35, and 2.37 microM,
      respectively. Compound 1 also displayed cytotoxicity against K-562 and NCI-H522
      cells with EC50 values of 5.04 and 4.80 microM, respectively.

PMID- 9934457
TI  - The use of neamine as a molecular template: inactivation of bacterial antibiotic
      resistance enzyme aminoglycoside 3'-phosphotransferase type IIa.
AB  - Aminoglycoside 3'-phosphotransferase type IIa [APH(3')-IIa] is a member of the
      family of bacterial aminoglycoside-modifying enzymes. Bacteria that harbor these
      enzymes are resistant to aminoglycoside antibiotics. Four aminoglycoside-based
      affinity inactivators were synthesized and were shown to be both substrates and
      inactivators for APH(3')-IIa. These affinity inactivators are N-bromoacetylated
      derivatives of neamine, an aminoglycoside antibiotic, where the bromoacetyl
      moiety in each was introduced regiospecifically at a different amine of the
      parent compound.

PMID- 9934458
TI  - The use of neamine as a molecular template: identification of active site
      residues in the bacterial antibiotic resistance enzyme aminoglycoside 3'
      phosphotransferase type IIa by mass spectroscopy.
AB  - Four novel aminoglycoside-based affinity inactivators were shown to covalently
      modify the active site of aminoglycoside 3'-phosphotransferase type IIa (APH(3')
      IIa), an important resistance factor in bacteria for aminoglycoside antibiotics.
      Standard peptide mapping techniques failed with this enzyme. A novel mass
      spectroscopic analysis which combines protease digestion on the instrument probe,
      followed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) is described which permitted rapid identification of the sites of protein
      modification. By this new technique, Glu-3 and Asp-23 were identified as active
      site residues, the side chains of which potentially may serve as counter ions for
      the ammonium functionalities at positions 6', and 1 and 3 of the antibiotic
      substrates, respectively. These findings contradict previous assertions that the
      C-terminal third of the enzyme should form the active site, by placing the active
      site clearly in the N-terminal portion of the enzyme.

PMID- 9934459
TI  - Design and synthesis of new secretory phospholipase A2 inhibitor of a
      phospholipid analog.
AB  - All stereoisomers of N-acyl-4,5-disubstituted oxazolidinone phospholipid analogs
      were synthesized by regio and stereoselective epoxide ring opening accompanied by
      introduction of an amino group. The (4R,5S)-derivative showed stronger inhibitory
      activity toward type II phospholipase A2 than the 4-substituted oxazolidinone
      phospholipid analog previously reported.

PMID- 9934460
TI  - Synthesis and antiplatelet effects of an isoxazole series of glycoprotein
      IIb/IIIa antagonists.
AB  - Despite the excellent in vitro potency of a series of benzamide glycoprotein
      IIb/IIIa antagonists, which have been reported previously, poor in vivo potency
      in the inhibition of platelet aggregation was observed when the most potent
      inhibitor XU057 was dosed intravenously to dogs. In this communication, we report
      that replacement of the benzamide in XU057 with an isoxazolecarboxamide resulted
      in significant improvement in in vivo potency. More importantly, the analogue
      XU065 showed an excellent oral antiplatelet effect in dogs.

PMID- 9934461
TI  - Synthesis and structure-activity relationships of adenosine analogs as inhibitors
      of trypanosomal glyceraldehyde-3-phosphate dehydrogenase. Modifications at
      positions 5' and 8.
AB  - A number of 5', N6- and C8, N6-disubstituted adenosine analogs was synthesized
      and tested for inhibition of trypanosomal glyceraldehyde 3-phosphate
      dehydrogenase. The most active compound, N6-(3-methyl-2-butenyl)-8-(2
      thienyl)adenosine, had Kl of 9 microM and was marginally selective for the
      parasite enzyme.

PMID- 9934462
TI  - Methionine analogues as inhibitors of methionyl-tRNA synthetase.
AB  - A series of methionine analogues have been synthesized as inhibitors of methionyl
      tRNA synthetase and evaluated for their inhibitory activities of E. coli
      methionyl-tRNA synthetase and bacterial growth. Among them, L-methionine
      hydroxamate 20 has proved to be the best inhibitor of the enzyme with Ki = 19
      microM and showed a growth inhibition against E.coli JM 109, P. vulganis 6059 and
      C. freundii 8090.

PMID- 9934463
TI  - Inhibition stereochemistry of hydroxamate inhibitors for thermolysin.
AB  - N-Acyl-N-hydroxy-beta-amino acid derivatives were prepared and tested as
      inhibitors for thermolysin to find that these inhibitors show the L
      stereospecificity in contrast to the corresponding hydroxamates prepared from
      alpha-amino acid, which exhibit the D-stereochemistry. N-Formyl-N-hydroxy-beta-L
      Phe-NHMe is the most potent inhibitor having the Ki value of 1.66 microM.

PMID- 9934464
TI  - Cytotoxic cycloartane-type triterpenes from Combretum quadrangulare.
AB  - Seven novel cycloartane-type triterpenes were isolated from Combretum
      quadrangulare, and their structures were elucidated on the basis of spectral
      analysis. All these compounds were tested for their cytotoxicity against murine
      colon 26-L5 carcinoma cells. Methyl quadrangularate B (2) and methyl
      quadrangularate D (4) exhibited potent cytotoxicity having ED50 values 9.54 and
      5.42 microM, respectively.

PMID- 9934465
TI  - Potent and selective thrombin inhibitors featuring hydrophobic, basic P3-P4
      aminoalkyllactam moieties.
AB  - Crystal structure and evolving SAR considerations of potent, selective
      benzylsulfonamide lactam thrombin inhibitors and related serine protease
      inhibitors have led to the design of novel thrombin inhibitors 1a-g, featuring
      hydrophobic, basic, P4-alkylaminolactam scaffolds that serve as novel types of P3
      P4 dipeptide mimics. The design, synthesis, and biological activity of these
      targets is presented.

PMID- 9934466
TI  - Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3
      ligands.
AB  - The 2-isopropyl thiazolyl group is a highly optimized P3 ligand for C2 symmetry
      based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we
      report that incorporation of this P3 ligand into a piperazine hydroxyethylamine
      series also yielded novel, highly potent inhibitors. In tissue culture assays,
      the presence of human serum was less deleterious to the activity of these
      inhibitors than to that of ritonavir. Furthermore, potent activity against
      ritonavir resistant HIV was observed.

PMID- 9934467
TI  - Unsymmetric nonpeptidic HIV protease inhibitors containing anthranilamide as a
      P2' ligand.
AB  - A series of novel unsymmetrical anthranilamide-containing HIV protease inhibitors
      was designed. The structure-activity studies revealed a series of potent P2-P3'
      inhibitors that incorporate an anthranilamide group at the P2' position. A
      reduction in molecular weight and lipophilicity is achieved by a judicious choice
      of P2 ligands (i.e., aromatic, heteroaromatic, carbamate, and peptidic). A
      systematic investigation led to the 5-thiazolyl carbamate analog 8 m, which
      exhibited a favorable Cmax/EC50 ratio (> 30), plasma half-life (> 8 h), and
      potent in vitro antiviral activity (EC50 = 0.2 microM).

PMID- 9934468
TI  - Synthesis and phototoxic property of tetra- and octa-glycoconjugated
      tetraphenylchlorins.
AB  - New tetraphenylchlorin derivatives having four or eight glucose molecules were
      synthesized. Phototoxicity against the HeLa cell, singlet oxygen producing
      ability, and cell permeability were examined to evaluate the activity on
      photodynamic therapy of the compounds.

PMID- 9934469
TI  - Organometallic flavonoid derivatives as spectroscopic probes.
AB  - Derivatives of naringenin have been synthesized with organometalcarbonyl
      reporting groups for IR spectroscopy attached at C-2, C-3', or C-6, and the
      products have been tested for the induction of nod gene expression using a
      Rhizobium leguminosarum strain which contains the Escherichia coli lacZ (beta
      galactosidase) gene fused to nodABC. Derivatives with an OMe substituent within
      the reporting group moiety showed residual gene induction activity.

PMID- 9934470
TI  - Design and synthesis of a novel class of nucleotide analogs with anti-HCMV
      activity.
AB  - A novel class of cyclic nucleotide analogs has shown anti-HCMV activity. The
      synthesis as well as structure-activity relationship studies are presented.

PMID- 9934471
TI  - Identification of novel nucleotide phosphonate analogs with potent anti-HCMV
      activity.
AB  - We have recently described the discovery of new leads in the area of anti-HCMV
      research. Further structure-activity relationship studies have allowed us to
      identify potent and selective anti-HCMV nucleotide analogs. The synthesis as well
      as structure-activity relationship studies are described.

PMID- 9934472
TI  - Phenylpiperazine derivatives with strong affinity for 5HT1A, D2A and D3
      receptors.
AB  - Four 7-[3-(4-phenyl-1-piperazinyl)propoxy]coumarins were synthesized. The
      affinities of these compounds for DA (D2A, D3) and 5HT1A receptors were evaluated
      for their ability to displace [3H]-raclopride and [3H]-8-OH-DPAT respectively
      from their specific binding sites. The affinities of the target compounds were
      all in the nanomolar range and followed the order 5-HT1A > D2 > D3.

PMID- 9934473
TI  - Butyrophenone analogues in the carbazole series: synthesis and determination of
      affinities at D2 and 5-HT2A receptors.
AB  - We describe a practical and efficient route for synthesis of 2-aminomethyl
      1,2,3,9-tetrahydro-4H-carbazol-4-ones using an effective Fisher indole
      methodology. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with pKi
      (5-HT2A/D2) ratio of 1.28 show an antipsychotic profile according to Meltzer's
      classification.

PMID- 9934474
TI  - Development of 2,2-dimethylchromanol cysteinyl LT1 receptor antagonists.
AB  - A new series of cysLT1 receptor antagonists represented by CP-288,886 (7) and CP
      265,298 (8) were developed which are equipotent to clinical cysLT1 receptor
      antagonists Zafirlukast (1) and Pranlukast (2).

PMID- 9934475
TI  - The discovery of orally available thrombin inhibitors: studies towards the
      optimisation of CGH1668.
AB  - The chemical optimisation of CGH1668 1 is described employing an in vivo model of
      absorption to determine the influence on bioavailability of single point
      modifications to five key molecular templates. The discovery of an orally
      bioavailable and selective thrombin inhibitor, 24, highlights the utility of this
      approach.

PMID- 9934476
TI  - Facile synthesis of high affinity styrylpyridine systems as inherently
      fluorescent ligands for the estrogen receptor.
AB  - A series of styrylpyridine derivatives containing two phenols was prepared via an
      efficient two-step synthesis. These compounds were designed to maximize the
      estrogen receptor binding affinity of a known series of inherently fluorescent
      styrylpyridines. While significant improvements were achieved in receptor
      affinity, the fluorescence intensity of this series of compounds is poor.

PMID- 9934477
TI  - Tracermer signal generators: an arborescent approach to the incorporation of
      multiple chemiluminescent labels.
AB  - The synthesis, conjugation, and chemiluminescent evaluation of zero, first, and
      second order acridinium-based Tracermer signal generators are described. Members
      of this family of labels have potential use as tracers in diagnostic assays and
      are structurally similar to arborol dendrimers. Tracermer-BSA conjugates showed
      up to a sixfold increase in light emission compared to the normal acridinium
      label.

PMID- 9934478
TI  - O-(fluoresceinylmethyl)hydroxylamine (OFMHA): a fluorescent reagent for detection
      of damaged nucleic acids.
AB  - 5- and 6-O-(Fluoresceinylmethyl)hydroxylamine (OFMHA, 5a, b) were prepared from
      the corresponding bis-pivaloyl-protected hydroxymethylfluoresceins (1a, b) in 50
      70% yield. The hydroxylamine derivatives reacted smoothly with the abasic sites
      present in acid/heat stressed calf thymus DNA.

PMID- 9934479
TI  - Novel acylguanidine containing thrombin inhibitors with reduced basicity at the
      P1 moiety.
AB  - Replacement of the noragmatine group in thrombin inhibitors with a beta-alanyl
      guanidine group resulted in a nearly equipotent and more selective compound 8
      despite the fact that the pKa of this P1 moiety is five orders of magnitude
      lower. Further modification resulted in a nonpeptide inhibitor with this beta
      alanyl-guanidine group, compound 28. This is an active and selective thrombin
      inhibitor and in view of its nonpeptide/low basicity structure selected for
      further pharmacological studies.

PMID- 9934480
TI  - The solid phase synthesis of a series of tri-substituted hydantoin ligands for
      the somatostatin SST5 receptor.
AB  - A series of trisubstituted hydantoins has been prepared by a versatile solid
      phase route employing primary alcohols, amines and amino acids as the monomeric
      building blocks. Several compounds showed submicromolar affinity in binding
      assays at recombinant human somatostatin receptors.

PMID- 9934481
TI  - Tricyclic ureas: a new class of HIV-1 protease inhibitors.
AB  - A new class of tricyclic ureas containing a conformationally constrained proline
      was designed with the aid of molecular modeling. Efficient stereoselective
      intermolecular pinacol coupling represented the highlight of the synthesis. These
      rigid cyclic ureas are active towards HIV-1 protease, with 9 being the most
      potent compound (Ki = 9 nM) despite interacting with only three side chain
      binding pockets of HIV protease.

PMID- 9934482
TI  - (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6- pentamethylpiperidin-4
      yl)-2,4-pentadienamide, a novel, potent and selective inhibitor of the osteoclast
      V-ATPase.
AB  - Optimisation of a novel series of osteoclast ATPase inhibitors led to (2Z,4E)-5
      (5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6- pentamethylpiperidin-4-yl)-2,4
      pentadienamide (1) that was the most potent compound in an in vitro osteoclast
      ATPase assay and in human bone resorption assays. Two of the possible geometric
      isomers have also been prepared and shown to be significantly less potent than 1.

PMID- 9934483
TI  - Synthesis of 6(alpha, beta)-aminocholestanols as ergosterol biosynthesis
      inhibitors.
AB  - delta 7-5-Desaturase catalyses one of the last steps in ergosterol biosynthesis
      in fungi. Moreover delta 5-unsaturation is necessary for the sparking function.
      Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as
      potential growth inhibitors. Preliminary results suggest that 6 beta
      aminocholestanol is a potent antifungal agent.

PMID- 9934484
TI  - Design, synthesis, and conformational analysis of a novel series of HIV protease
      inhibitors.
AB  - A combination of structure-based design and both solution, and solid-phase
      synthesis were utilized to derive a potent (nM) series of HIV-1 protease
      inhibitors bearing a structurally novel backbone. Detailed structural analysis of
      several inhibitors prepared in this series has suggested that rigidification of
      the P1/P2 region of this class of molecules may result in compounds with improved
      potency.

PMID- 9934485
TI  - Design and synthesis of novel conformationally restricted HIV protease
      inhibitors.
AB  - A set of HIV protease inhibitors represented by compound 2 has previously been
      described. Structural and conformational analysis of this compound suggested that
      conformational restriction of the P1/P2 portion of the molecule could lead to a
      novel set of potent protease inhibitors. Thus, probe compounds 3-7 were designed,
      synthesized, and found to be potent inhibitors of HIV protease.

PMID- 9934486
TI  - Synthesis of gem-difluoro-avermectin derivatives: potent anthelmintic and
      anticonvulsant agents.
AB  - A series of gem-difluoro-avermectin derivatives was synthesized from the
      corresponding ketones at positions 4", 4', 13, and 23 using diethylaminosulfur
      trifluoride (DAST). These fluorinated avermectins exhibit potent antiparasitic
      activity in a new Haemonchus contortus larval assay and are equipotent to
      ivermectin. In addition, 23-gem-difluoro-ivermectin displays useful
      anticonvulsant activity in mouse models.

PMID- 9934487
TI  - N6-(5,6-epoxynorbornyl)adenosine analogs as A1 adenosine agonists.
AB  - A range of related adenosines and 5'-N-ethylcarboxamidoadenosines bearing
      oxygenated substituents in the N6 position have been synthesised and evaluated as
      A1-adenosine receptor ligands. Compound 9 emerged with potent affinity (EC50 =
      1.1 nM).

PMID- 9934488
TI  - Synthesis and guanase inhibition studies of a novel ring-expanded purine analogue
      containing a 5:7-fused, planar, aromatic heterocyclic ring system.
AB  - The synthesis of a novel planar, potentially aromatic, ring-expanded xanthine
      analogue (1), containing the 5:7-fused imidazo[4,5-e][1,4]diazepine ring system,
      along with guanase inhibition studies are reported. The compound was synthesized
      in six steps, starting from 1-benzyl-5-nitroimidazole-4-carboxylic acid (2), and
      was biochemically screened against rabbit liver guanase. Compound 1 is a moderate
      competitive inhibitor of the enzyme with a Ki of 2.27 +/- 0.66 x 10(-4) M.

PMID- 9934489
TI  - Synthesis and biological activity of [Tic5] didemnin B.
AB  - A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic
      acid) as a conformationally restrained replacement for tyrosine has been
      synthesized and shown to have comparable potency as a protein biosynthesis
      inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in
      the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot
      macrocyclization.

PMID- 9934490
TI  - Differential activity of rosiglitazone enantiomers at PPAR gamma.
AB  - Analysis of the enantiomers of rosiglitazone in a PPAR gamma binding assay
      suggests that the (S)-(-)-isomer is responsible for the antidiabetic activity.

PMID- 9934491
TI  - Novel cytokine release inhibitors. Part III: Truncated analogs of tripterine.
AB  - Truncated analogs of tripterine as cytokine (IL-1 alpha, IL-1 beta, TNF-alpha, IL
      6, and IL-8) release inhibitors are discussed.

PMID- 9934492
TI  - Tobramycin-EDTA conjugate: a noninnocent affinity-cleaving reagent.
AB  - The design, synthesis, and ribozyme inhibitory activity of a novel EDTA
      aminoglycoside conjugate are reported. This affinity cleaving reagent is a
      noninnocent RNA binder: its RNA affinity, judged by its ability to inhibit the
      hammerhead ribozyme HH16, is different than the parent natural product and is
      markedly dependent on the oxidation state of the chelated metal ion.

PMID- 9934493
TI  - Conjugation of oligonucleotides via an electrophilic tether: N
      chloroacetamidohexyl phosphoramidite reagent.
AB  - A novel method for the preparation of oligonucleotides conjugated with
      nucleophilic ligands is described. A new phosphoramidite building block derived
      from N-chloroacetyl-6-aminohexanol is attached at the 5'-terminus on the last
      step of oligonucleotide synthesis. Postsynthetic treatment of support-bound
      modified oligonucleotide with a variety of amines and mercaptans affords
      conjugates in high yield.

PMID- 9934494
TI  - Benzothiopyran-4-one based reversible inhibitors of the human cytomegalovirus
      (HCMV) protease.
AB  - A novel class of CMV protease inhibitors based on a benzothiopyran-S,S-dioxide
      nucleus has been discovered. Enzyme kinetic data supports a reversible mode of
      inhibition for a representative member of this class, 2-(3-pyridyl-N
      oxide)benzothiopyran-4-one-S,S-dioxide, 1. Experiments in the presence and
      absence of the disulfide reducing agent DTT suggest that the inhibition by 1 is
      not due to oxidative inactivation of the enzyme. Also presented are results of
      some SAR studies of the benzothiopyranone ring system.

PMID- 9934495
TI  - Alkoxide-catalyzed ring-opening of a novel homosaccharin derivative: synthesis of
      potent, selective P3-lactam thrombin inhibitors containing P4-o
      alkoxycarbonylbenzylsulfonamide residues.
AB  - A series of lactam derivatives 1b-g featuring P4-o
      alkoxycarbonylbenzylsulfonamide residues along with the potential P4
      homosaccharin prodrug candidate 1h was prepared in order to probe the thrombin S3
      specificity pocket. The synthesis and alkoxide-catalyzed ring opening of the
      novel homosaccharin intermediate 7 followed by subsequent elaboration delivered
      the targets 1b-h which were potent and selective thrombin inhibitors. The design,
      synthesis, and biological activity of these targets will be presented.

PMID- 9934497
TI  - [Heat shock proteins and heart protection].

PMID- 9934496
TI  - Synthesis and transporter binding properties of (R)-2 beta, 3 beta- and (R)-2
      alpha, 3 alpha-diaryltropanes.
AB  - (R)-2-Aryl-2-tropinone (9) was synthesized from (R)-2-carbomethoxy-3-tropinone
      (5) and was used as the key intermediate for the synthesis of (R)-2 beta, 3 beta-
      and (R)-2 alpha, 3 alpha-diaryltropanes. Inhibition of radioligand binding
      studies at the dopamine, serotonin, and norepinephrine transporters showed that
      the (R)-3 beta-(4-methylphenyl)-2 beta-phenyltropane (3b, RTI-422) possessed an
      IC50 value of 1.96 nM at the dopamine transporter and was highly selective for
      this transporter relative to the serotonin and norepinephrine transporters.

PMID- 9934498
TI  - [Effect of vagus nerve stimulation on the rat heart rate during blocking of beta
      adrenergic receptors with obzidan].

PMID- 9934499
TI  - [Apolipoproteins A-I, B and E levels during intensive physical exertion and
      during recovery period].

PMID- 9934500
TI  - [Characteristics of epithelium-dependent smooth muscle contraction in various
      regions of the respiratory tract].

PMID- 9934501
TI  - [Reflection of individual properties of autonomic nervous system in the type of
      autonomic and behavioral reactions during emotional-pain stress].

PMID- 9934502
TI  - [Age-related characteristics of epithelium-smooth muscle interaction in the rat
      trachea].

PMID- 9934503
TI  - [Reactions of granulocytic hematopoietic stem cells during experimental neurosis
      inducing situations].

PMID- 9934504
TI  - [Biotransformation of xenobiotics in the liver of rats with different resistance
      to hypoxia during exposure to cold].

PMID- 9934505
TI  - [Reaction of biogenic amines in lymph nodes to exposure to millimeter-range
      extremely high frequency electromagnetic irradiation].

PMID- 9934506
TI  - [Effect of diazepam on the transmembrane potential and physico-chemical state of
      thymocyte membranes in rats during exposure to cold].

PMID- 9934507
TI  - [Effect of spreading cortical depression on the activity of sensory neurons from
      the trigeminal complex].

PMID- 9934508
TI  - [Effect of angiotensin II on the DNA synthesis in the myocardium and epithelial
      tissues of newborn albino rats].

PMID- 9934509
TI  - [Changes in platelet aggregation during irradiation of blood with helium-neon
      laser and red light diodes].

PMID- 9934510
TI  - [Effect of thyrotropin on activity of calpains in the thyroid gland. The role of
      second messengers].

PMID- 9934511
TI  - [Effect of single whole-body irradiation of rats on the reproductive system and
      vitamin levels in organs of the offspring].

PMID- 9934513
TI  - [Comparison of the effect of various contrast media on the in vitro
      chemiluminescence of peritoneal macrophages of rats].

PMID- 9934512
TI  - [Antiarrhythmic effect of the antiopioid peptide nociceptin and its effect on
      fast Na+-channels in cardiomyocytes].

PMID- 9934514
TI  - [Effect of the gamma-aminobutyric acid derivative, TZ-50-2, on the systemic and
      cardiac hemodynamics, and the size of myocardial necrosis area].

PMID- 9934515
TI  - [Computer analysis of microimages of adrenal glands during poisoning with
      organochlorine compounds].

PMID- 9934516
TI  - [Differences in the antiopsonin activity of extracellular products of S. aureus
      and N, gonorrheae].

PMID- 9934517
TI  - [Weak carcinogen protects against the effect of strong carcinogen not requiring
      the metabolic activation].

PMID- 9934518
TI  - [Ultrastructural localization of protein-4 binding insulin-like growth factors in
      cow follicles].

PMID- 9934519
TI  - [The role of peptide hydra morphogen during the early postnatal development of
      rats].

PMID- 9934520
TI  - [Magnetic shielding of vertebrate brain].

PMID- 9934521
TI  - [Effect of potassium orotate on the reversibility of cirrhotic changes and
      regeneration of the rat liver].

PMID- 9934522
TI  - [Crystallization of oral fluid. Composition and purity of the feeder surface].

PMID- 9934523
TI  - Strategies and measures for our next century.
AB  - The centennial of the Medical Library Association offers an opportunity to
      reflect with some satisfaction on accomplishments and to consider the future. The
      Western Governors University is an illustration of the dynamic future.
      Professional values constitute both distinguishing characteristics and steadfast
      guides for succeeding in this complex environment. Powerful collaborative
      technologies now make it possible to overcome challenges that are beyond the
      capabilities of an individual librarian or library. Providing organized access to
      the Internet exemplifies these challenges. The profession has a strong history of
      cooperation but to take full advantage of collaboration, institutional and
      cultural barriers must be overcome. The National Network of Libraries of Medicine
      (NN/LM) should be the facilitating agent in this process.

PMID- 9934524
TI  - The digital library: an oxymoron?
AB  - "Virtual libraries" and "digital libraries" have become stock phrases of our
      times. But what do they really mean? While digital refers to a new form of
      document encoding and must be approached from that perspective, virtual resonates
      with aspects that modern philosophy treats with benign neglect at best. The word
      virtual harbors the notion of potential, and therein lies its hidden strength.
      Although strong commercial interests try to use the shift to a digital
      environment to redefine the political economy of knowledge, and thus virtualize
      libraries into a state of almost complete impotence, all hope is not lost.
      Librarians of virtualized libraries may well discover that they have re-empowered
      institutions if they place human interaction at the heart of their operations. In
      other words, rather than envisioning themselves as knowledge bankers sitting on
      treasure vaults of knowledge, they should see themselves as "hearts" dynamizing
      human communities. They should also see themselves as an essential part of these
      communities, and not as external repositories of knowledge. In this fashion, they
      will avoid the fate of becoming an oxymoron.

PMID- 9934525
TI  - Measurements of journal use: an analysis of the correlations between three
      methods.
AB  - Rapid journal price increases have made essential that libraries have reliable
      and efficient measures of the importance of individual journals to local
      clientele. Three key measures are in-house use, circulation, and citation by
      faculty. This paper examines the correlations between these three measures at an
      academic health sciences library. Data were gathered from 1992 to 1994 using each
      of the three methods. Each set of data was compared with the other two, and for
      each pair of data sets both Spearman Rank Order and Pearson Product-Moment
      correlation coefficients were calculated to examine the degree of correlation
      between the two sets. All of the correlation coefficients were positive and
      statistically significant (P < 0.0001). This information suggests that if
      gathering many types of use data is impractical, one method may be used with the
      confidence that it correlates with other types of use. Visual inspection of the
      data confirms this with one exception: many clinical review titles tend to have a
      low local citation rate but high in-house use and circulation rates, suggesting
      that these are being used for educational and clinical purposes but not for
      research.

PMID- 9934526
TI  - Developing a culture of lifelong learning in a library environment.
AB  - Between 1995 and 1996, the Annette and Irwin Eskind Biomedical Library (EBL) at
      Vanderbilt University Medical Center (VUMC) radically revised the model of
      service it provides to the VUMC community. An in-depth training program was
      developed for librarians, who began to migrate to clinical settings and establish
      clinical librarianship and information brokerage services beyond the library's
      walls. To ensure that excellent service would continue within the library, EBL's
      training program was adapted for library assistants, providing them with access
      to information about a wide variety of work roles and processes over a four to
      eight-month training period. Concurrently, customer service areas were
      reorganized so that any question--whether reference or circulation--could be
      answered at any of four service points, eliminating the practice of passing
      customers from person to person between the reference and circulation desks. To
      provide an incentive for highly trained library assistants to remain at EBL,
      management and library assistants worked together to redesign the career pathway
      based on defined stages of achievement, self-directed participation in library
      wide projects, and demonstrated commitment to lifelong learning. Education and
      training were the fundamental principles at the center of all this activity.

PMID- 9934527
TI  - An assessment of collections at the University of Wisconsin-Madison Health
      Sciences Libraries: drug resistance.
AB  - In December 1997, the authors completed an in-depth collection assessment project
      at the University of Wisconsin-Madison Health Sciences Libraries. The purpose was
      to develop a framework for future collection assessment projects by completing a
      multifaceted evaluation of the libraries' monograph and serial collections in the
      subject area of drug resistance. Evaluators adapted and synthesized several
      traditional collection assessment tools, including shelflist measurement,
      bibliography and standard list checking, and citation analysis. Throughout the
      project, evaluators explored strategies to overcome some of the problems inherent
      in the application of traditional collection assessment methods to the evaluation
      of biomedical collections. Their efforts resulted in the identification of
      standard monographs and core journals for the subject area, a measurement of the
      collections' strength relative to the collections of benchmark libraries, and a
      foundation for future collection development within the subject area. The
      project's primary outcome was a collection assessment methodology that has
      potential application to both internal and cooperative collection development in
      medical, pharmaceutical, and other health sciences libraries.

PMID- 9934528
TI  - Use of fuzzy set theory to extend Dhawan's journal selection model: ranking the
      biomedical informatics serials.
AB  - OBJECTIVE: Experts disagree on the parameters to use to identify the "best"
      serials within a scientific field. The author set out to develop an extension to
      Dhawan's journal selection model for ranking serials in any scientific field.
      METHODS: Comparison of three different instantiations of Dhawan's model were used
      to rank thirty-four biomedical informatics serials. RESULTS: The first
      instantiation of Dhawan's model identified seven serials and divided them into
      two groups. The second instantiation of Dhawan's model identified twelve serials
      and separated them into two groups. Using fuzzy set theory the new extended model
      produced a rank ordered list of the top twelve biomedical informatics serials.
      CONCLUSIONS: Use of fuzzy set theory to assign set membership and combine data in
      Dhawan's journal selection model allows one to: (1) eliminate the need to
      determine arbitrary cutoff points for inclusion of serials within each of
      Dhawan's evaluation criteria categories, (2) combine data from disparate sources,
      and (3) obtain a rank-ordered list of the biomedical informatics serials rather
      than simply identifying a set of the "top" serials. Such a ranked list provides
      librarians and researchers alike with the information necessary to help them make
      their biomedical informatics serial selection decisions based on objective,
      quantifiable data.

PMID- 9934529
TI  - Feasibility and marketing studies of health sciences librarianship education
      programs.
AB  - The University of North Carolina at Chapel Hill evaluated five curricular models
      designed to improve education for health sciences librarianship. Three of the
      models enhanced existing degree and certificate programs, and two were new
      programs for working information professionals. Models were developed with input
      from experts and a Delphi study; the marketability of the models was tested
      through surveys of potential students and employers; and recommendations were
      made as a guide to implementation. The results demonstrated a demand for more
      specialized curricula and for retraining opportunities. Marketing data showed a
      strong interest from potential students in a specialized master's degree, and mid
      career professionals indicated an interest in postmaster's programs that provided
      the ability to maintain employment. The study pointed to the opportunity for a
      center of excellence in health sciences information education to enable health
      sciences librarians to respond to their evolving roles.

PMID- 9934530
TI  - Factors affecting the diffusion of online end user literature searching.
AB  - OBJECTIVES: The aim of this study was to identify factors that affect diffusion
      of usage of online end user literature searching. Fifteen factors clustered into
      three attribute sets (innovation attributes, organizational attributes, and
      marketing attributes) were measured to study their effect on the diffusion of
      online searching within institutions. METHODS: A random sample of sixty-seven
      academic health sciences centers was selected and then 1,335 library and
      informatics staff members at those institutions were surveyed by mail with
      electronic mail follow-up. Multiple regression analysis was performed. RESULTS:
      The survey yielded a 41% response rate with electronic mail follow-up being
      particularly effective. Two dependent variables, internal diffusion (spread of
      diffusion) and infusion (depth of diffusion), were measured. There was little
      correlation between them, indicating they measured different things. Fifteen
      independent variables clustered into three attribute sets were measured. The
      innovation attributes set was significant for both internal diffusion and
      infusion. Significant individual variables were visibility for internal diffusion
      and image enhancement effects (negative relation) as well as visibility for
      infusion (depth of diffusion). Organizational attributes were also significant
      predictors for both dependent variables. No individual variables were significant
      for internal diffusion. Communication, management support (negative relation),
      rewards, and existence of champions were significant for infusion. Marketing
      attributes were not significant predictors. CONCLUSIONS: Successful diffusion of
      online end user literature searching is dependent on the visibility of the
      systems, communication among, rewards to, and peers of possible users who promote
      use (champions). Personal image enhancement effects have a negative relation to
      infusion, possibly because the use of intermediaries is still seen as the more
      luxurious way to have searches done. Management support also has a negative
      relation to infusion, perhaps indicating that depth of diffusion can increase
      despite top-level management actions.

PMID- 9934531
TI  - Assessing and enhancing medical students' computer skills: a two-year experience.
AB  - In 1984, the Association of American Medical Colleges (AAMC) issued
      recommendations for the reform of medical education. One recommendation was that
      information sciences be incorporated into the medical curriculum. In fall 1996, a
      survey was conducted to learn more about computer use by medical students at the
      Rockford regional site of the University of Illinois at Chicago College of
      Medicine. The purpose of the survey was to gather information not only about
      computer skills, but also about overall comfort level in using computers and
      about expectations for enhancing computer skills while attending medical school.
      Over a two year period, 208 students representing four classes received this
      survey in their e-mail. Non-respondents received a follow-up print copy in their
      student mailboxes. Results, based on a 60% response rate, showed a majority of
      Rockford students entered medical school with good skills in using e-mail and
      word processing, but many lacked the skills necessary to search the medical
      literature or to use computer-assisted instructional programs. Overall, 80% of
      students expected to learn more about computers while attending medical school.
      Results contributed to an increased effort to integrate computer applications
      into the medical curriculum and to use computers as a means of communicating with
      students.

PMID- 9934532
TI  - Promoting interaction between organizations of medical librarians and health care
      professionals.

PMID- 9934533
TI  - Nitric oxide: from a mysterious labile factor to the molecule of the Nobel Prize.
      Recent progress in nitric oxide research.
AB  - NO is now known to be an important messenger molecule in biology. It regulates a
      variety of functions within cells and tissues including vasodilation,
      neurotransmission and immunological process. This review will focus on the nitric
      oxide synthase gene family and recent progress on molecular genetic analysis of
      NOS1, NOS2 and NOS3 genes.

PMID- 9934534
TI  - Amphibian metamorphosis as a model for studying the developmental actions of
      thyroid hormone.
AB  - The thyroid hormones L-thyroxine and triiodo-L-thyronine have profound effects on
      postembryonic development of most vertebrates. Analysis of their action in
      mammals is vitiated by the exposure of the developing foetus to a number of
      maternal factors which do not allow one to specifically define the role of
      thyroid hormone (TH) or that of other hormones and factors that modulate its
      action. Amphibian metamorphosis is obligatorily dependent on TH which can
      initiate all the diverse physiological manifestations of this postembryonic
      developmental process (morphogenesis, cell death, re-structuring, etc.) in free
      living embryos and larvae of most anurans. This article will first describe the
      salient features of metamorphosis and its control by TH and other hormones.
      Emphasis will be laid on the key role played by TH receptor (TR), in particular
      the phenomenon of TR gene autoinduction, in initiating the developmental action
      of TH. Finally, it will be argued that the findings on the control of amphibian
      metamorphosis enhance our understanding of the regulation of postembryonic
      development by TH in other vertebrate species.

PMID- 9934535
TI  - Posterior gut development in Drosophila: a model system for identifying genes
      controlling epithelial morphogenesis.
AB  - The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian
      tubules, provides a simple, well-defined system where it is possible to use a
      genetic approach to define components essential for epithelial morphogenesis. We
      review here the advantages of Drosophila as a model genetic organism, the
      morphogenesis of the epithelial structures of the posterior gut, and what is
      known about the genetic requirements to form these structures. In overview,
      primordia are patterned by expression of hierarchies of transcription factors;
      this leads to localized expression of cell signaling molecules, and finally, to
      the least understood step: modulation of cell adhesion and cell shape. We
      describe approaches to identify additional genes that are required for
      morphogenesis of these simple epithelia, particularly those that might play a
      structural role by affecting cell adhesion and cell shape.

PMID- 9934536
TI  - Construction of a DNA library from chromosome 4 of rice (Oryza sativa) by
      microdissection.
AB  - A simple method to create a chromosome-specific DNA library of rice, including
      microdissection, amplification, characterization and cloning, is described. Rice
      chromosome 4 from a metaphase cell has been isolated and amplified by the Linker
      Adapter PCR (LA-PCR). The PCR products were labeled as probes with DIG-11-dUTP
      using the random priming method. Southern blot analysis with rice genomic DNA and
      specific RFLP markers demonstrated that the PCR products were derived from rice
      chromosome 4. A large library comprising over 100,000 recombinant plasmid
      microclones from rice chromosome 4 was constructed. Colony hybridization showed
      that 58% of the clones contained single or low-copy sequences and 42% contained
      repetitive sequences. The size of inserts generated by PCR ranged from 140bp to
      500bp. This method will facilitate cloning of the specific chromosome DNA markers
      and important genes of rice.

PMID- 9934537
TI  - The kinetics of IL-4 and IFN-gamma gene expression in mice after Trichosansin
      immunization.
AB  - Trichosanthin (TCS) is a potent allergen to mice. According to our previous
      experiments, it could bring out the IgE response to ovabumin (OVA) if TCS was
      given one day before OVA immunization, while OVA alone could not induce IgE to
      it. In this work, the kinetics of interleukin 4(IL-4) and interferon gamma(IFN
      gamma) gene expression in the mesenteric lymph node (MLN) of TCS-immunized mice
      was investigated using a semi-quantitative RT-PCR method. It indicated that TCS
      induced significant IL-4 gene expression and the peaks of IL4 gene expression
      were on day one after TCS immunization in both primary and secondary response. In
      contrast, the IFN-gamma gene expression was suppressed. Furthermore, the IL-4
      gene expression in the secondary response was lower than that in the primary
      response. Thus the presence of IgE memory B cells were studied. Results showed
      that the amount of mature IgE mRNA arose significantly and rapidly one day after
      TCS restimulation, while in the MLN of the mice primed 30 days before and without
      boost, it was almost as the same amount of the unimmunized control. These
      findings suggest the existence of the IgE memory B cells in the mice after the
      primary TCS immunization.

PMID- 9934538
TI  - Carboxyl terminal of rhodopsin kinase is required for the phosphorylation of
      photo-activated rhodopsin.
AB  - Human rhodopsin kinase (RK) and a carboxyl terminus-truncated mutant RK lacking
      the last 59 amino acids (RKC) were expressed in human embryonic kidney 293 cells
      to investigate the role of the carboxyl terminus of RK in recognition and
      phosphorylation of rhodopsin. RKC, like the wild-type RK, was detected in both
      plasma membranes and cytosolic fractions. The C-terminal truncated rhodopsin
      kinase was unable to phosphorylate photo-activated rhodopsin, but possesses
      kinase activity similar to the wild-type RK in phosphorylation of small peptide
      substrate. It suggests that the truncation did not disturb the gross structures
      of RK catalytic domain. Our results also show that RKC failed to translocate to
      photo-activated rod out segments. Taken together, our study demonstrate the
      carboxyl terminus of RK is required for phosphorylation of photo-activated
      rhodopsin and strongly indicate that carboxyl-terminus of RK may be involved in
      interaction with photo-activated rhodopsin.

PMID- 9934539
TI  - Val 70, Phe 72 and the last seven amino acid residues of C-terminal are essential
      to the function of norepinephrine transporter.
AB  - The norepinephrine transporter(NET) is a member of the Na+/Cl- dependent
      neurotransmitter transporter family and constitutes the target of several
      clinically important antidepressants. To delineate the critical amino acid
      residues and the function of C-terminal in regulating transport activity of NET,
      here we constructed two site mutants (V70F, F72V; V70I, F72V) and one C-terminal
      truncated mutant (delta 611-617). The wild type and mutants of NET were expressed
      in Xenopus oocytes by injection of their cRNA. We found that all of these mutants
      lost their transport activity. These results indicate that the amino acid
      residues of V70 and F72, and the last seven amino acids of C-terminal are
      essential to the transport activity of NET.

PMID- 9934540
TI  - Expression of cytokine mRNA during immuno-modulation of murine suppressor
      macrophages.
AB  - In order to analyze the mechanism of immuno-modulation by LPS on murine
      peritoneal suppressor macrophages, we have, using RNase protection assay, checked
      the changes of mRNA expression pattern of several cytokine genes during the
      immuno-modulation. It has been found that, after treating peritoneal suppressor
      macrophages with LPS, mRNAs of IL-12 p35, IL-12 p40, IL-6 and IFN-gamma are newly
      appeared, while those of IL-1 alpha, IL-1 beta and IL-1Ra are increased and those
      of other cytokines, like TGF-beta 1 and MIF are not changed at all. It seems
      certain that those cytokines, whose expression is increased by LPS stimulation,
      may be responsible for the functional changes of suppressor macrophages during
      immuno-modulation. Among these changes, the appearance of IL-12 mRNA may play a
      critical role, and, in this regard, the synergetic effect between IFN-gamma and
      LPS on the increase of IL-12 p35 and Il-12 p40 mRNA expression is an interesting
      finding.

PMID- 9934541
TI  - The use of an IpaC-specific ELISA to identify enteroinvasive Escherichia coli
      strains of unusual serogroups.
AB  - Twenty five Escherichia coli isolates expressing O antigens different from the
      conventionally recognized enteroinvasive E. coli were tested in the Sereny test,
      with an invasion plasmid-specific DNA probe, and by an enzyme-linked
      immunosorbent assay recognizing the secreted IpaC antigen. These results indicate
      that the IpaC enzyme-linked immunosorbent assay is a sensitive method to
      recognize enteroinvasive E. coli, irrespective of their serogroups.

PMID- 9934542
TI  - LCx: a diagnostic alternative for the early detection of Mycobacterium
      tuberculosis complex.
AB  - This study aims to evaluate the performance of a new diagnostic method (LCx
      Tuberculosis Assay, Abbott Laboratories) based on Ligase Chain Reaction (LCR)
      technology, for the detection of Mycobacterium tuberculosis in respiratory and
      non-respiratory specimens and compare it with standard microbiological data and
      the clinical diagnosis of tuberculosis. Nine hundred specimens were collected
      from patients with a high suspicion of tuberculosis (740 respiratory samples and
      160 non-respiratory specimens). The study was divided into two separate groups:
      samples washed and distilled water (207 samples) and unwashed samples that were
      directly resuspended in phosphate buffer (693 samples). The overall sensitivity,
      specificity, positive and negative predictive values of samples washed with
      distilled water after decontamination with SDS-NaOH were: 54%, 100%, 100%, and
      94%, respectively. If these results were divided according to origin of
      specimens, the sensitivity, specificity, positive and negative predictive values
      in respiratory and non-respiratory samples were 54.5%, 100%, 100%, 94% and 50
      100%, 100%, 93%, respectively. In contrast, for the non-washed samples, values
      were 85%, 95%, 80% and 98%, respectively. Respiratory and non-respiratory samples
      gave values of 84%, 96%, 77%, and 97.5% versus 89%, 99%, 94%, and 98%. The LCx M.
      tuberculosis assay is a novel, semi-automated assay and a rapid and highly
      specific technique for screening all forms of tuberculosis, including non
      respiratory forms.

PMID- 9934543
TI  - Clinical and pharmacological evaluation of a modified cefotaxime bid regimen
      versus traditional tid in pediatric lower respiratory tract infections.
AB  - It is generally accepted that the treatment of community-acquired pneumonia,
      either in adults or in pediatric patients, is mainly empirical. Thus, the
      treatment selection must fulfill both the epidemiological requirements, according
      to the most frequently described pathogens, and the pharmacological criteria to
      ensure adequate and prolonged drug concentrations at the infection site, to reach
      clinical efficacy. Cefotaxime has proven to be effective in this indication when
      traditionally administered three times daily and, more recently, twice daily, as
      a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To
      gain further evidence using this updated dosing schedule, 258 pediatric patients
      with lower respiratory tract infections were treated with cefotaxime 100
      mg/kg/day, administered as a twice daily or three times daily regimen. In the
      cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of
      clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the
      cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete
      resolution of clinical signs and symptoms. Both drug schedules were well
      tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing
      schedules showed comparability. The serum half-life of desacetylcefotaxime was
      marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for
      desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3
      mg/kg doses, respectively). Results from this study support the use of twice
      daily cefotaxime administration for the treatment of lower respiratory tract
      infections in pediatric patients.

PMID- 9934544
TI  - In vitro activity of meropenem against common pathogenic bacteria isolated in
      Taiwan.
AB  - The in vitro antimicrobial activity of meropenem, in comparison with nine other
      antimicrobial agents, against 12 different common pathogenic bacteria were
      evaluated to know the susceptibility of common bacteria to meropenem in Taiwan.
      Meropenem was active against most Gram-positive, Gram-negative, and anaerobic
      bacteria, including methicillin-sensitive Staphylococcus aureus, Streptococcus
      pyogenes, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae,
      Enterobacter cloacae, Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter
      baumannii, Haemophilus influenzae, and Bacteroides fragilis. For many of them,
      meropenem was the most active one in comparison with other broad-spectrum
      cephalosporins, aztreonam, imipenem, and ciprofloxacin. It is concluded that
      meropenem is a very active agent against most common pathogenic bacteria. It is
      uncommon for these common bacteria, except MRSA and Stenotrophomonas maltophilia,
      to be resistant to meropenem in Taiwan, where a high prevalence of resistance to
      other antimicrobial agents was found in many of the common bacteria.

PMID- 9934545
TI  - Multicenter survey of the in vitro activity of four expanded-spectrum beta
      lactams against consecutive contemporary clinical isolates.
AB  - A survey of the in vitro susceptibility of consecutive clinical bacterial
      isolates to cefotaxime, ceftazidime, cefpodoxime, and aztreonam was conducted at
      10 North American medical centers during the first quarter of 1997. All four
      drugs had good activity against Enterobacteriaceae and fastidious Gram-negative
      bacteria and poor activity against enterococci and methicillin-resistant
      staphylococci. No significant trends in susceptibility to cefotaxime or
      ceftazidime were observed when compared with a previous similar survey. The use
      of cefpodoxime MIC > 2.0 micrograms/mL as a marker for extended-spectrum beta
      lactamase production by Escherichia coli and Klebsiella spp. had good
      sensitivity, but the specificity was very poor for E. coli. Thus, at least for E.
      coli, this screening test seems to be of questionable value unless used to
      indicate the need for additional tests such as clavulanic acid inhibition. Disk
      diffusion zone diameters correlated well with the MICs for all four drugs and
      support the current interpretive criteria.

PMID- 9934546
TI  - Antimicrobial susceptibility patterns for pathogens isolated from patients in
      Latin American medical centers with a diagnosis of pneumonia: analysis of results
      from the SENTRY Antimicrobial Surveillance Program (1997). SENTRY Latin America
      Study Group.
AB  - Pneumonia is the most common fatal hospital-acquired infection, with attributable
      mortality rates ranging from 30 to 60%. Rapid initiation of optimal antimicrobial
      therapy is essential for obtaining treatment success. In this report the
      antimicrobial susceptibility of 556 strains from the lower respiratory tract were
      collected by the SENTRY Antimicrobial Surveillance Program (1997). These strains
      were isolated from hospitalized patients with pneumonia in 10 Latin American
      centers (6 countries) as part of this 68-center worldwide program. The isolates
      were susceptibility tested against more than 70 drugs (35 reported) by the
      reference broth microdilution method. Klebsiella pneumoniae and Escherichia coli
      phenotypically consistent with extended spectrum beta-lactamase (ESBL) production
      were characterized further by ribotyping and pulsed-field gel electrophoresis.
      The five most frequently isolated species were (n/%): Pseudomonas aeruginosa
      (149/26.8%), Staphylococcus aureus (127/22.8%), Acinetobacter spp. (66/11.9%),
      Klebsiella spp. (56/10.1%), and Enterobacter spp. (40/7.2%). P. aeruginosa
      demonstrated high rates of resistance to a majority of the antimicrobial drugs
      tested. Carbapenems, amikacin, and piperacillin/tazobactam demonstrated the
      highest susceptibility rates (73.8-77.2%) against P. aeruginosa, however the
      lowest resistance rate was observed for cefepime (6.7%). Acinetobacter spp. also
      showed very high rates of resistance and the most active compounds were imipenem
      and meropenem (89.0% susceptibility) followed by the tetracyclines. Cephalosporin
      susceptibilities among Klebsiella spp. were low: cefoxitin, 73.0%; ceftazidime,
      69.4%; and ceftriaxone, 65.9%. Approximately 37% and 28% of K. pneumoniae and E.
      coli isolates, respectively, were considered ESBL producers based on NCCLS
      criteria. Ceftriaxone was active against only 52.5% of Enterobacter spp.
      isolates, whereas cefepime was active against 90.0% of isolates (MIC50, < or =
      0.12 microgram/mL). Oxacillin resistance was detected in nearly 50% of S. aureus
      isolates. The most active drugs against S. aureus were vancomycin, teicoplanin,
      and quinupristin/dalfopristin (MIC90, 1 microgram/mL). In summary, our study of
      pneumonias in Latin American medical centers demonstrated a greatly increased
      prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative
      bacilli when compared with similar controlled studies from North America.

PMID- 9934547
TI  - Facial cellulitis and Pseudomonas luteola bacteremia in an otherwise healthy
      patient.
AB  - Pseudomonas luteola is an aerobic, Gram negative rod, formerly classified as CDC
      group Ve-1 and Chryseomonas luteola. It is an uncommon clinical isolate. A
      previously healthy 59-year-old homosexual man with facial cellulitis and
      Pseudomonas luteola bacteremia is reported. Previously reported cases of P.
      luteola bacteremia have occurred in association with pancreatic abscess,
      prosthetic valve endocarditis, cardiac surgery, granulomatous hepatitis,
      peritonitis, and indwelling vascular catheters. This case suggests that the
      spectrum of disease caused by this bacteria may continue to expand.

PMID- 9934548
TI  - Antimicrobial activity of gatifloxacin tested against Neisseria gonorrhoeae using
      three methods and a collection of fluoroquinolone-resistant strains.
AB  - Gatifloxacin, a new 8-methoxy fluoroquinolone, was tested against 131 strains of
      Neisseria gonorrhoeae by reference agar dilution, disk diffusion, and Etest (AB
      BIODISK, Solna, Sweden) methods on supplemented GC agar. Gatifloxacin activity
      was equal to ciprofloxacin (MIC50, 0.008 microgram/mL) against strains fully
      susceptible to fluoroquinolones, but was generally four-fold more active (MIC90,
      0.064-0.094 microgram/mL) against strains with par C or gyr A mutations and
      resistance to ciprofloxacin. Etest results were comparable to those generated by
      the agar dilution test [correlation coefficient (r) = 0.97]. Gatifloxacin zone
      diameters using 5-microgram disks also correlated well (r = 0.86-0.87) with the
      agar dilution and Etest MIC results. Breakpoints for laboratory testing of
      Neisseria gonorrhoeae strains await clinical trial outcome correlations, but
      susceptibility at < or = 0.125 or < or = 0.25 microgram/mL (> or = 34 mm) seems
      appropriate. All three tests used in this study seem applicable for laboratory
      testing of isolates from patients with uncomplicated gonorrhoeae receiving
      therapy with gatifloxacin.

PMID- 9934549
TI  - The prevalence of fluoroquinolone resistance among clinically significant
      respiratory tract isolates of Streptococcus pneumoniae in the United States and
      Canada--1997 results from the SENTRY Antimicrobial Surveillance Program.
AB  - As part of the SENTRY antimicrobial resistance surveillance program, a total of
      1100 clinically significant respiratory tract isolates of Streptococcus
      pneumoniae were tested for susceptibility to six fluoroquinolone antimicrobial
      agents: ciprofloxacin, levofloxacin, gatifloxacin, grepafloxacin, sparfloxacin,
      and trovafloxacin. Isolates were obtained during the 5-month period, February to
      June, 1997 from 27 United States medical center laboratories and seven
      laboratories in Canadian health care institutions. All testing was performed in a
      single center. Of 1100 test strains, 3 (0.3%), all from different U.S. centers,
      were fluoroquinolone resistant. Among the remaining 1097 fluoroquinolone
      susceptible isolates, the rank order of activity among the six agents tested in
      this study was grepafloxacin (modal MIC = 0.25 microgram/mL) = trovafloxacin
      (modal MIC = 0.25 microgram/mL) = sparfloxacin (0.25 microgram/mL) > gatifloxacin
      (0.5 microgram/mL) > levofloxacin (1 microgram/mL) = ciprofloxacin (1
      microgram/mL). Fluoroquinolone resistance is currently uncommon among respiratory
      tract isolates of S. pneumoniae in North America, but there exist clear
      differences between the in vitro activities of different fluoroquinolones for
      this organism.

PMID- 9934550
TI  - Extended spectrum beta-lactamase production and fluorquinolone resistance in
      pathogens associated with community acquired urinary tract infection.
AB  - We have evaluated the susceptibility of 199 pathogens isolated in pure culture
      from consecutive urine samples submitted from the community. Rates of
      susceptibility for all organisms were ampicillin, 48%; amoxycillin/clavulanic
      acid, 88%; cephalothin, 57%; cefuroxime axetil, 74%; nalidixic acid, 85%;
      ciprofloxacin, 99%; nitrofurantoin, 78%; and trimethoprim, 67%. Ciprofloxacin
      resistance and production of extended spectrum beta-lactamase enzymes were
      detected in Escherichia coli strains isolated from patients in the community.

PMID- 9934551
TI  - Pharyngeal branchial cyst: magnetic resonance findings.
AB  - An unusual case of pharyngeal cyst in a 25-year-old man studied by Magnetic
      Resonance (MR) is described. Anatomic location and pathological findings
      indicated the second branchial pouch origin.

PMID- 9934552
TI  - Preoperative staging of thyroid papillary carcinoma with ultrasonography.
AB  - OBJECTIVE: To evaluate the usefulness of ultrasonography including Doppler flow
      imaging for the preoperative staging of thyroid papillary carcinoma. MATERIALS
      AND METHODS: In 77 patients with thyroid papillary carcinoma who underwent total
      thyroidectomy, the accuracy of ultrasonography in preoperative clinical staging
      was assessed with use of pathologic examination on the basis of TNM
      classification by the International Union Against Cancer (UICC). RESULTS: In 63
      (81.8%) cases, T categories were estimated accurately. The sensitivity in
      depicting tumor extension into the prethyroidal muscle and/or the
      sternocleidomastoid muscle was 77.8%, whereas the sensitivity for invasion into
      the trachea and the esophagus was 42.9 and 28.6%, respectively. In 37 (48.1%)
      cases, N categories were underestimated, and the sensitivity in the detection of
      regional lymph node metastasis was 36.7%. Doppler flow imaging was performed in
      36 patients, and no correlation was found between flow patterns and the presence
      of local invasion or regional lymph node metastasis. CONCLUSION: Ultrasonography
      was useful for preoperative investigation of thyroid papillary carcinoma, but
      several limitations existed, especially in evaluating extracapsular invasion to
      deep locations and regional lymph node metastasis.

PMID- 9934553
TI  - Endobronchial tumours in childhood.
AB  - Endobronchial tumours are rare in childhood and are not often considered in the
      differential diagnosis of persistent pneumonitis and atelectasis. We present the
      clinical and radiological features of seven cases of childhood bronchial
      'adenoma' seen at our hospital over a 16-year period. Because they are relatively
      slow growing, prompt diagnosis and early surgical treatment offer the best chance
      of cure in these patients. A review of the literature is given.

PMID- 9934554
TI  - Value of digital fluoroscopy for the diagnosis of pneumatosis coli.
AB  - Two cases are presented of benign pneumatosis coli diagnosed on digital
      fluoroscopic barium enema examinations, in which the gas-filled cysts in the
      colonic wall were only recognized by postprocessing of the images (i.e.
      increasing the brightness and contrast settings) at the computer workstation.
      When digital barium enemas are performed, we therefore recommend image
      postprocessing to evaluate polypoid lesions in order to differentiate pneumatosis
      coli from true colonic neoplasms.

PMID- 9934555
TI  - Acute suppurative thyroiditis secondary to piriform sinus fistula: a case report.
AB  - We present a typical case of acute suppurative thyroiditis (AST), associated with
      a piriform sinus fistula. We illustrate the case with an ultrasound picture of a
      hypoechogenic perithyroid mass and a CT scan using intravenous iodine contrast
      showing a perithyroid hypodense mass with peripheral enhancement, the mass also
      having intrathyroid involvement. When clinical and radiological findings suggest
      the presence of AST, it is necessary to rule out the presence of a piriform sinus
      fistula by means of a radiological study with barium contrast. Piriform sinus
      fistula is a rare abnormality derived from the branchial arch which is directly
      related to recurrent episodes of AST; surgical excision is hence, necessary to
      avoid such episodes.

PMID- 9934556
TI  - A case of aneurysmal bone cyst in father and son.
AB  - The authors report a familial case of primary aneurysmal bone cyst in father and
      son, affecting both at the same location at nearly the same age. This fact again
      raises the speculation of a genetic link as another factor in the pathogenesis of
      aneurysmal bone cyst.

PMID- 9934557
TI  - The haemodynamic effects of iodinated water soluble radiographic contrast media:
      a review.
AB  - All classes of iodinated water-soluble radiographic contrast media (RCM) are
      vasoactive with the iso-osmolar dimers inducing the least changes in the vascular
      tone. The mechanisms responsible for RCM-induced changes in the vascular tone are
      not fully understood and could be multifactorial. A direct effect on the vascular
      smooth muscle cells causing alterations in the ion exchanges across the cell
      membrane is thought to be an important factor in RCM-induced vasodilatation. The
      release of the endogenous vasoactive mediators adenosine and endothelin may also
      play a crucial role in the haemodynamic effects of RCM particularly in the
      kidney. In addition, the effects of RCM on blood rheology can cause a reduction
      in the blood flow in the microcirculation. The purpose of this review is to
      discuss the pathophysiology of the haemodynamic effects of RCM and to offer some
      insight into the biology of the endothelium and vascular smooth muscle cells as
      well as the pharmacology of the important vasoactive mediators endothelin and
      adenosine.

PMID- 9934558
TI  - Comparison of CT and MRI features in sinusitis.
AB  - OBJECTIVE: To correlate the features of inflammatory changes in the paranasal
      sinuses on magnetic resonance imaging (MRI) with computed tomography (CT).
      METHODS AND PATIENTS: One hundred and fourteen patients with histologically
      proven nasopharyngeal carcinoma (NPC) were staged with both CT and MRI. All CT
      and MRI images of patients with mucosal thickening but no tumour involvement of
      the sinuses were retrospectively analysed. RESULTS: There were inflammatory
      changes in 36 maxillary, 21 sphenoid and 16 ethmoid sinuses. These changes
      include mucosal thickening, retention cysts, retained secretions, inspissated
      secretions and dystrophic calcification. MRI is superior to CT in separating
      thickened mucosa, retained secretions and retentions cysts. CONCLUSION: It is
      important to appreciate CT changes of sinusitis and the corresponding spectrum of
      MRI features.

PMID- 9934559
TI  - The helical three-dimensional CT in the diagnosis of torticollis with
      occipitocondylar hypoplasia.
AB  - Congenital anomalies of the atlanto-occipital and atlantoaxial joints are rare.
      Those most commonly reported are atlantoaxial instability, basilar impression,
      anomalies of the odontoid process, laxity of the transverse atlantal ligament and
      atlanto-occipital fusion. Occipital condylar hypoplasia is infrequent and
      difficult to recognise. We recently diagnosed it using helical 3D CT in
      association with torticollis in two patients. The first patient had a several
      year history of torticollis. The second patient had acute cervical lymphadenitis
      associated with post-operative torticollis. 3D CT distinctly revealed
      atlantoaxial subluxation with hypoplasia of the occipital condyles in both cases.

PMID- 9934560
TI  - Usefulness of the non-distension of the stomach in the evaluation of perigastric
      invasion in advanced gastric cancer by CT.
AB  - The purpose of this study was to evaluate by CT the usefulness of the non
      distension of the stomach in determining invasion of the gastric cancer into
      perigastric space and adjacent organs. Forty-eight patients with pathologically
      proved gastric cancer were studied by conventional CT. Patients were examined
      using two techniques: (a) non-distension of the stomach in the supine position
      and 34 patients additionally in prone position; and (b) distension of the stomach
      with water or air in the supine and/or prone position. CT findings by both
      techniques were separately analysed preoperatively and compared to surgical
      findings. Invasion of perigastric fat was better demonstrated by the non
      distension technique in 15 of the 36 patients with pathologically proven fat
      infiltration. Non-distension technique was more accurate than distension in
      detecting: (a) involvement of gastric ligaments (80 versus 67% for gastrohepatic,
      85 versus 73% for gastrocolic and 80% by both techniques for gastrosplenic
      ligament); (b) perigastric lymphadenopathy (86% by both techniques for lymph
      nodes sited at the gastrohepatic ligament, 85 versus 75% for gastrocolic and 85
      versus 80% for gastrosplenic ligament lymph nodes, respectively); and (c)
      pancreatic invasion (86 versus 80%). The prone position with non-distended
      stomach was particularly helpful in excluding pancreatic invasion in five
      patients with carcinoma of the gastric body. The distension technique was more
      accurate in demonstrating perigastric extension in gastroesophageal junction
      tumors in two patients. In conclusion, additional CT of the non-distended stomach
      with the patient in prone position can provide further evidence about
      infiltration of the perigastric fat, ligaments, lymph nodes and pancreas, in
      patients with gastric carcinoma, with the exception of gastroesophageal junction
      tumors.

PMID- 9934561
TI  - X-linked deafness with stapes gusher in females.
AB  - A 22-year-old woman presented with severe mixed hearing loss and a flow of
      cerebrospinal fluid in the middle ear during stapes surgery (stapes gusher). HRCT
      of the temporal bones showed characteristic abnormalities of the inner ear
      (bulbous dilatation of the lateral portion of the internal acoustic meatus with
      incomplete separation from the cochlea, and widening of the first part of the
      facial nerve canal) described in X-linked progressive mixed deafness with stapes
      gusher. The evaluation of the patient's family revealed a sister with the same
      clinical history and identical HRCT findings, and 11 normal male relatives. This
      is the first report with typical findings of this entity that affects only female
      members of a family, suggesting another type of inheritance.

PMID- 9934562
TI  - Ossification of the ligament flavum.
AB  - A total of 82 patients who underwent spinal computed tomographic scan, in an 8
      month period at the King Khalid University Hospital, Riyadh, Saudi Arabia, were
      analyzed for age, sex, the presence/absence, site, and type of ossification of
      the ligamentum flavum (OLF) as well as associated diseases. The OLF was
      radiographically present (bilaterally or unilaterally) as linear (74.5%) or
      nodular types (25.5%). The linear type was especially seen at the inner aspects
      of the ligamentum flavum. OLF was present in 35.4% of patients, and was seen at
      single and multiple levels in 51% and 41% of them, respectively. OLF was
      identified in a total of 47 levels in the study group and was associated with
      other disease in the spine in 38 (81%) of these levels. In none of the patients
      was OLF the cause of myelopathy. The incidence of OLF and its pathogenesis and
      significance are discussed. This paper is the first report of OLF from the Middle
      East. OLF in this part of the world is usually asymptomatic.

PMID- 9934563
TI  - Social construction and materiality: the limits of indeterminacy in therapeutic
      settings.
AB  - By drawing parallels between the courtroom testimony of a Christian Science
      practitioner and an intersession conversation between systemic family therapists,
      I critique the abstract idealism of language-centered social constructionism. I
      argue that social constructionist inquiry that highlights the indeterminacy of
      meaning without a corresponding emphasis on the responsive embodied practices of
      family members glosses over the material conditions shaping the politics of
      interaction. The implications of this problem are discussed as they relate to the
      setting of family therapy, where social construction theory is often used to
      guide practical interventions.

PMID- 9934564
TI  - The place of material in a constructed world.

PMID- 9934565
TI  - The place of the constructed in a materially responsive world.

PMID- 9934566
TI  - Understanding betrayals in marriage: a synthesized model of forgiveness.
AB  - Forgiveness is an issue that is problematic for many couples, particularly those
      in marital therapy. However, little attention has been paid to this construct in
      the psychological literature. The purpose of this article is to describe a
      synthesized model of forgiveness using constructs from multiple theories,
      including forgiveness, trauma recovery, cognitive-behavioral, family systems, and
      insight-oriented theories. Forgiveness is conceptualized as a process consisting
      of three stages, each of which has cognitive, behavioral, and affective
      components. Furthermore, these stages seem to parallel a person's natural
      response to traumatic stress. First, there is a response to the initial impact;
      second, there is an attempt to give the event some kind of meaning, or put it
      into context; and finally, the person begins to move forward and readjust.
      Forgiveness is conceptualized as attaining: (a) a realistic, nondistorted,
      balanced view of the relationship; (b) a release from being controlled by
      negative affect toward the participating partner; and (c) a lessened desire to
      punish the participating partner. Implications for marital therapy also are
      discussed.

PMID- 9934567
TI  - Not just a time-out: change dynamics of prayer for religious couples in conflict
      situations.
AB  - For religious couples, the spiritual domain stands alongside biological,
      psychological, and systemic domains as an influence upon interaction and
      mechanism for change. A qualitative methodology consisting of structured
      interviews of religious spouses was used to investigate effects of prayer on
      couple interaction during conflict. A reliable description of the dynamics of
      prayer across spouse interviews was extracted by four analysts using a group
      interpretive procedure. Findings suggest that prayer invokes a couple-God system,
      which significantly influences couple interaction during conflict. Overall,
      prayer appears to be a significant "softening" event for religious couples,
      facilitating reconciliation and problem solving. Prayer 1) invokes an experience
      of relationship with Deity; 2) deescalates hostile emotions and reduces emotional
      reactivity; 3) enhances relationship and partner orientation and behavior; 4)
      facilitates empathy and unbiased perspective; 5) increases self-change focus; and
      6) encourages couple responsibility for reconciliation and problem solving.
      Therapists' support of religious couples' use of prayer as a change mechanism is
      considered.

PMID- 9934568
TI  - Marital conflict by proxy after father kills mother: the family therapist as an
      expert witness in court.
AB  - The father killing the mother leaves the children effectively without parents.
      The extended family from both sides will often intervene to offer a home for the
      children, or at least to have a say in what arrangements are made for the
      children and how they are to be brought up. Intensely competitive and hostile
      feelings between the opposing sets of relatives are commonly aroused, and the
      children may be caught up in a battle reminiscent of the conflict between their
      parents, which culminated in the death of their mother. I and my colleagues have,
      as a team, seen more than 300 children who have lost one parent at the hands of
      the other, and we have been involved in subsequent custody battles as expert
      witnesses. Based on this experience and using this context as an example, the
      issues for the family therapist as expert witness in adversarial Court
      proceedings are presented. A case is described that illustrates the theoretical
      exposition--including the effectiveness of family therapy from the witness box.

PMID- 9934569
TI  - Reading against the lines: resisting foreclosure in therapy discourse.
AB  - In this article, it is noted that poststructural ideas can be useful tools in
      fostering reflexivity and creativity for clinicians. By examining the process of
      meaning construction, clinicians can detach from repetitive interpretations of
      therapy discourse that lead to conversational closure. Four strategies for
      guiding a reading of family therapy interaction are presented: incitement to
      discourse, deconstruction, normativity, and the cultural grid of intelligibility.
      These strategies are used to describe examples of marital therapy discourse. By
      learning to read therapy as discourse, clinicians may critically examine how
      meaning is constructed and use that awareness to foster therapeutic
      conversations.

PMID- 9934570
TI  - Family of origin and current relationship influences on codependency.
AB  - This study investigated codependency in Caucasian individuals within the
      framework of Bowen's Family Systems Theory. The sample consisted of a group of
      couples, in which one member of the couple was a recovering alcoholic in an
      aftercare program, and a group of matched, comparison couples. Participants
      completed a demographic questionnaire, the Friel Codependency Assessment
      Inventory, and the Personal Authority in the Family System (PAFS) Questionnaire.
      The findings confirmed that codependency levels were higher in clinical than in
      comparison couples. Moreover, within the clinical group, there was little
      difference between alcoholics and their spouses with respect to dysfunction in
      their families of origin, current families, or their codependency levels. The
      findings further suggested that the etiology and function of codependency are
      different in clinical and nonclinical families. In the clinical sample, the
      family of origin and current relationship characteristics were related to
      codependency in patterns consistent with previous theory and research. For the
      nonclinical sample, however, the findings contradicted conventional codependency
      theory. The findings suggest that, in contrast to clinical populations,
      codependency in nonclinical populations has some links with favorable
      characteristics of family functioning.

PMID- 9934571
TI  - The treatment of cluster headache.

PMID- 9934572
TI  - Anticardiolipin antibodies as an independent risk factor for stroke in young
      Saudis.
AB  - The role of the anticardiolipin (aCL) antibodies as a predisposing factor for
      cerebral ischemia in young Saudi patients was investigated in a total of 61 cases
      (41 males, 20 females; mean age: 34 years). Ten patients had aCL antibodies which
      were predominantly of the IgG isotype. The mean age and sex ratio of the aCL
      positive and aCL-negative cases were similar. The aCL-positive cases had
      significantly higher frequency of anti-DNA antibodies, lower frequency of HDL,
      and more prior stroke events and transient ischemic attacks than the aCL-negative
      cases (p < 0.05) on univariate analysis. However, with multivariate logistic
      regression analysis, only anti-DNA antibodies and HDL were significantly
      associated with aCL. Anticardiolipin antibodies represent an independent risk
      factor for stroke in young Saudi patients and aCL assessment should be considered
      in young patients with recurrent cerebral ischemia.

PMID- 9934573
TI  - Met-enkephalin increase in patients with fibromyalgia under local treatment.
AB  - Fibromyalgia is a chronic debilitating condition of unknown etiology. The
      clinical picture suggests increased activity and/or supersensitivity in
      nociceptive pathways or inadequate activity in endogenous pain attenuation
      mechanisms. One therapeutic approach in the treatment of this syndrome is the
      administration of serial local injections of lidocaine hydrochloride in the
      painful points. To evaluate the effect of this treatment on plasma met-enkephalin
      (ME) levels we studied 15 patients, all women with fibromyalgia under local
      treatment in the tender points, grouped as follows: 5 were treated with local
      injection of lidocaine hydrochloride, 5 were treated with local injection of
      saline and 5 treated with dry needling. Significant increases in plasma ME
      concentrations were observed in all groups in the last sampling of each session
      studied. These results show an increase in plasma ME levels 10 minutes after
      finishing each session, which is independent of the maneuver employed.

PMID- 9934575
TI  - A possible paradigm of functional neurology.
AB  - The basic approach of classic neurology cannot fully explain certain clinical
      neurological phenomena. The explanation in these cases requires an extension of
      the conceptual borders of neurology. We set out to present a possible paradigm of
      functional neurology.

PMID- 9934574
TI  - Radiofrequency cervical zygapophyseal joint neurotomy for cervicogenic headache:
      a prospective study of 15 patients.
AB  - The present study assessed the clinical efficacy of radiofrequency cervical
      zygapophyseal joint neurotomy in patients with cervicogenic headache. Fifteen
      consecutive patients with cervicogenic headache were treated and then assessed
      one week prior to treatment and, at short-term (8 weeks), intermediate (mean 8.8
      months) and long-term (mean 16.8 months) follow-ups. The following were taken as
      outcome parameters: Visual Analogue Scale (VAS), 7-point Verbal Rating Scale
      (VRS), number of headache days per week and analgesic intake per week. The
      results of this study showed that radiofrequency neurotomy of the cervical
      zygapophyseal joints significantly reduced headache severity in 12 (80%)
      patients, both at short-term and long-term follow-up assessed by 7-point VRS.
      Mean VAS decrease was 31.4 mm (p < 0.001) and 53.5 mm (p < 0.0001) respectively
      in this period. The average mean number of headache days per week decreased from
      5.8 days to 2.8 days (p = 0.001) and the average analgesic intake per week showed
      a reduction from a mean of 17.5 tablets to a mean of 3.4 tablets (p = 0.003). A
      definitive conclusion about the clinical efficacy of this treatment can only be
      drawn from a randomized controlled trial.

PMID- 9934576
TI  - Mapping of functional changes associated with administration of substances of
      abuse in the rat.
AB  - The [14C]2-deoxyglucose method allows us to investigate whether a drug affects
      cerebral functional activity in selected brain regions or along discrete neural
      pathways. Employment of the method in laboratory animals has shown that
      substances of abuse produce a wide variety of cerebral functional changes which
      depend upon a number of different variables including the kind of substance, the
      dose, the modality of administration, and the context. In spite of such a
      variability, different substances of abuse, when injected in a rat at doses, or
      with modalities effective in inducing self-administration, have in common the
      property of selectively modifying glucose utilization of the nucleus accumbens,
      in particular in the shell portion. It is likely that the change reflects a
      functional change of a neural circuitry which mediates motivational properties
      associated with addiction.

PMID- 9934577
TI  - Diversion colitis--new light through old windows.
AB  - Diversion proctocolitis is an iatrogenic disorder caused by surgical diversion of
      the faecal stream away from the colorectal mucosa. Such surgery may be necessary
      in cases of tumour, trauma or inflammatory conditions of the colorectum.
      Histopathological change is characterized by a chronic lymphoplasmacytic
      inflammatory infiltrate, and the hallmark feature, lymphoid follicular
      hyperplasia. Histological appearances are determined by the disease state of the
      colonic mucosa prior to faecal diversion. Macroscopic appearances may vary
      considerably, but often include aphthoid ulceration. The exact pathogenesis of
      the condition remains unclear, but the removal of short-chain fatty acids,
      present in the faecal stream, is considered an important aetiological factor.
      Current research areas, including the microbiology and cellular kinetics of
      diversion colitis, are discussed along with clinical features and treatments.

PMID- 9934578
TI  - Distinct clonal origin of low-grade MALT-type and high-grade lesions of a
      multifocal gastric lymphoma.
AB  - AIMS: Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma and high-grade
      B-cell non-Hodgkin's lymphoma (NHL) of the stomach may occur simultaneously. To
      determine the clonal relationship between these tumours, we compared the
      immunoglobulin heavy chain gene (IgH) rearrangements of low and high-grade
      components of a multifocal gastric NHL. METHODS AND RESULTS: The complementary
      determining region 3 (CDR3) of the IgH gene rearrangements were polymerase chain
      reaction (PCR) amplified, cloned and sequenced. The analysis of the CDR3
      sequences rearranged by tumour cells of low-grade MALT and the high-grade NHL
      revealed different nucleic acid sequences. CONCLUSION: These findings suggest
      that low-grade MALT and high-grade B-cell components of multifocal gastric NHL
      may represent unrelated clones.

PMID- 9934579
TI  - Origin of primary gastric T-cell lymphomas from intraepithelial T-lymphocytes:
      report of two cases.
AB  - AIMS: The classification of primary gastric T-cell lymphomas is uncertain due to
      the exceeding rarity of these tumours; many of the reported cases were felt to be
      similar to node-based lymphomas. We describe two cases of primary gastric T-cell
      lymphoma with evidence of origination from intraepithelial T-lymphocytes. METHODS
      AND RESULTS: Both tumours were restricted to the stomach; one displaying a large
      ulcerated mass, the other a widespread superficial tumour manifestation.
      Histologically the first tumour was composed of sheets of medium-sized lymphoid
      cells showing marked epitheliotropism at the edge of the ulcer, and a CD3+, CD4-,
      CD8-, CD20-, CD56-, CD103+, beta F1+ phenotype. The second case differed
      histologically and immunophenotypically from the first case. In addition to
      lamina propria and submucosal infiltration, the lymphoma contained an extensive
      intraepithelial component even in large areas without other evidence of tumour.
      The neoplastic cells ranged in size from small to medium and large.
      Immunohistology disclosed a CD3+, CD4+, CD8-, CD20-, CD56-, beta F1+ phenotype.
      Staining for CD103 could not be performed in this case since frozen material was
      not available. CONCLUSIONS: The prominent epitheliotropism, the marked
      intraepithelial growth and the expression of CD103 strongly imply a derivation of
      these primary gastric lymphomas from intraepithelial T-lymphocytes. Additional
      studies of larger series will clarify whether the findings described here are
      typical of primary gastric T-cell lymphomas.

PMID- 9934580
TI  - Phenotypic and cytotoxic characteristics of peripheral T-cell and NK-cell
      lymphomas in relation to Epstein-Barr virus association.
AB  - AIMS: We investigated the phenotypic and cytotoxic characteristics of different
      types of peripheral T-cell and NK-cell lymphomas and correlated the findings of
      cytotoxic phenotype with Epstein-Barr virus (EBV) association. METHODS AND
      RESULTS: Eighty cases of peripheral T-cell and NK-cell lymphomas, classified
      according to the REAL classification, were investigated for cytotoxic phenotype
      (by studying T-cell intracellular antigen-1 (TIA-1) expression
      immunohistochemically) and EBV association (by in situ hybridization for EBV
      encoded small non-polyadenylated RNAs), and the results were correlated with the
      specific clinicopathological types and the immunophenotype with special emphasis
      on CD56 expression and CD4/CD8 status. Overall, 39/80 cases (49%) expressed TIA
      1. Angiocentric lymphoma (23/24 cases; 96%), aggressive NK-cell leukaemia ('large
      granular lymphocyte (LGL) leukaemia') (3/3 cases; 100%), intestinal T-cell
      lymphoma (5/6 cases; 83%) and anaplastic large cell lymphoma (4/6 cases; 67%)
      were the major subtypes showing a cytotoxic phenotype. Only four of the 27 cases
      (15%) of peripheral T-cell lymphoma, unspecified, were TIA-1+, while all the
      seven cases of angioimmunoblastic T-cell lymphoma, six cases of mycosis fungoides
      and one case of adult T-cell lymphoma/leukaemia were TIA-1-. CONCLUSIONS: Within
      the group of peripheral T-cell and NK-cell lymphomas, angiocentric lymphoma,
      aggressive NK-cell leukaemia ('LGL leukaemia'), intestinal T-cell lymphoma and
      anaplastic large cell lymphoma are the major subtypes displaying a cytotoxic
      phenotype. The relationships between the cytotoxic phenotype and EBV association,
      CD56 expression or CD4/CD8 status are secondary to the relationship between
      cytotoxic phenotype and specific lymphoma subtype.

PMID- 9934581
TI  - Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin
      expression during breast carcinogenesis and tumour progression: a comparative
      study with CD44.
AB  - AIMS: This study was performed to investigate whether immunohistochemical
      expression of E-cadherin (E-cad) and beta-catenin (beta-cat) in conjunction with
      CD44 may correlate with the clinical evolution and prognosis of breast cancer.
      METHODS AND RESULTS: One-hundred and forty-two routinely processed breast tissue
      samples including normal breast, benign lesions, in situ and invasive carcinomas
      were investigated. E-cad and beta-cat were strongly expressed by luminal and
      basal cells in normal glands, benign proliferative and early neoplastic
      intraductal lesions. Contrarily, CD44 was expressed exclusively by myoepithelial
      cells in normal breast, whereas different isoform expression patterns were
      observed in premalignant and malignant lesions. Simultaneous lack of E-cad/beta
      cat expression was detected in in situ and invasive lobular carcinomas in
      contrast to ductal lesions, in which the differential loss of the molecules was
      associated with poorer differentiation, irrespective of CD44 immunophenotype.
      Reduced E-cad (P = 0.003), beta-cat (P = 0.03) and increased CD44v4 (P = 0.005)
      and v7 (P = 0.007) expression were significantly associated with positive lymph
      node status. Decreased E-cad and lack of CD44v6 expression correlated with poor
      survival. There was no difference between the expression of either molecule in in
      situ and invasive components within the same tumour. CONCLUSIONS: Our results
      indicate that changes in E-cad, beta-cat and CD44 expression occur early in
      breast carcinogenesis; they are involved in tumour differentiation, but events
      additional to their deranged expression are needed to acquire an invasive
      phenotype.

PMID- 9934582
TI  - Cathepsin D in host stromal cells is associated with more highly vascular and
      aggressive invasive breast carcinoma.
AB  - AIMS: To determinate the relationship between tumoral angiogenesis and cathepsin
      D (CD) expression in tumour and host stromal cells of invasive breast carcinoma,
      and to examine its association with classical prognostic factors such as lymph
      node status, histological grade, tumour size, mitotic rate, peritumoral
      lymphovascular invasion and oestrogen receptor (ER) status. METHODS AND RESULTS:
      Sections from 102 invasive breast carcinoma were cut from the archival formalin
      fixed, paraffin-embedded tissue blocks and stained using immunohistochemistry for
      the endothelial cell adhesion molecule (CD31) and CD. Microvessel density was
      assessed by counting vessels in the three most vascular areas at x400 field. The
      counts were expressed as the highest counts within any x400 field. The evaluation
      of immunostaining for CD was performed separately in both the parenchymal and
      stromal cells. Microvessel density was correlated positively with histological
      grade and peritumoral lymphovascular invasion, and correlated inversely with ER
      status. Positive CD staining of tumour cells was more frequent in positive ER
      tumours and was not significantly associated with the other classical prognostic
      factors. However, moderate to strong staining of host cells was correlated with
      higher histological grade, higher mitotic index and lack of ER protein. There was
      a statistically significant association between CD expression of host stromal
      cells and higher vessel count. CONCLUSIONS: CD in host stromal cells is
      associated with more aggressive tumours and with a higher intratumoral
      microvessel density. Evaluation of CD in combination with angiogenic activity may
      be of some help in more accurately predicting the biological behaviour of breast
      carcinoma.

PMID- 9934583
TI  - Immunohistochemical assessment of p170 provides prognostic information in
      endometrial carcinoma.
AB  - AIMS: To determine the significance of proliferative activity (PA) in endometrial
      carcinomas, we analysed the expression of cell cycle-related antigens in
      routinely processed tissue. METHODS AND RESULTS: Serial sections of 164
      endometrial carcinoma specimens were immunostained with the monoclonal antibodies
      (MoAb) Ki-S4 (specificity for p170) and Ki-S5 (specificity for p320/350). The Ki
      S4 PA (median value 18.3%) and Ki-S5 PA (median value 25.0%) in endometrial
      carcinomas showed a significant correlation (r = 0.89, P < 0.001). A
      significantly lower median value of Ki-S4 and Ki-S5 immunoreactivity was
      ascertained in endometrial carcinomas stage I vs. > I (P < 0.05), in tumours with
      myometrial invasion < or = 50% vs. > 50% (P < 0.03), and in grade 1 vs. grade 2
      and 3 tumours (P < 0.001). Univariate analysis showed that age, FIGO stage and
      grade, histopathological subtype, myometrial invasion, Ki-S4 and Ki-S5 PA
      provided prognostic information on the adjusted overall survival, whereas FIGO
      stage (P = 0.002) and Ki-S4 PA (P = 0.008) were independent prognosticators for
      adjusted overall survival in multivariate analysis. CONCLUSIONS: The association
      with established prognosticators for endometrial carcinomas, and the results of
      uni- and multivariate analysis indicates that the additional evaluation of Ki-S4
      PA is useful for classifying patients into subgroups with low and high risk of
      relapse which might help individualizing the therapeutic strategy in endometrial
      cancer patients.

PMID- 9934584
TI  - High metallothionein expression is associated with features predictive of
      aggressive behaviour in endometrial carcinoma.
AB  - AIMS: Metallothioneins (MTs) are a group of ubiquitous low molecular weight
      proteins with a high affinity for heavy metal ions. The aim of the present study
      was to investigate MT expression in a series of endometrial carcinomas. We wished
      to determine whether MT expression in endometrial carcinoma was related to
      established prognostic factors such as tumour grade, stage and histological type.
      We also wanted to establish if high MT expression in curettings of endometrial
      carcinoma was predictive of high expression in the subsequent hysterectomy
      specimen. METHODS AND RESULTS: Sixty-three cases of endometrial carcinoma were
      included in the study. These comprised 57 endometrioid adenocarcinomas (15 grade
      1, 25 grade 2, 17 grade 3), three papillary serous adenocarcinomas, two mucinous
      adenocarcinomas and one clear cell adenocarcinoma. Forty-five tumours were stage
      I, 10 were stage II and eight were stage III. In 28 cases, diagnostic endometrial
      curettings, performed prior to hysterectomy, were available for study.
      Immunohistochemical staining was performed using the anti-MT monoclonal antibody
      E9. The intensity and distribution of MT staining were assessed using a
      semiquantitative method. This resulted in an intensity distribution (ID) score
      out of a maximum of 300. The mean ID score of grade 1 and 2 endometrioid
      adenocarcinomas was 67 and 63, respectively, while for grade 3 tumours the mean
      ID score was 114. This was statistically significant (P = 0.05). The three
      papillary serous adenocarcinomas had high ID scores with a mean of 208. The mean
      ID score of stage I tumours was 69. This was lower than those of stage II and III
      tumours which had mean ID scores of 116 and 128, respectively. However, these
      differences were not statistically significant (P = 0.288). A significant
      correlation was observed between MT ID scores in endometrial curettings and in
      the subsequent hysterectomy (P = 0.013). CONCLUSIONS: MT isoforms can be
      demonstrated in most endometrial adenocarcinomas. High MT ID scores are
      associated with high grade and high stage endometrial adenocarcinomas and with
      the aggressive papillary serous adenocarcinoma. Whether this is of value as an
      independent prognostic factor has yet to be established.

PMID- 9934585
TI  - Primary malignant peripheral nerve sheath tumour of the heart.
AB  - AIMS: Malignant peripheral nerve sheath tumour (MPNST) is an unusual sarcoma of
      the heart and should be differentiated from other spindle cell sarcomas. METHODS
      AND RESULTS: We combined morphological, immunohistochemical and cytogenetic
      techniques in the differential diagnosis, particularly from monophasic synovial
      sarcoma. The tumour consisted of dense fascicles, alternating with hypocellular,
      myxoid zones. There was a marked herniation of tumour cells into the vascular
      lumen. Immunohistochemically, the tumour cells expressed vimentin and focally
      S100 protein. There was no expression of cytokeratin or epithelial membrane
      antigen (EMA). Although we found a complex karyotype, the finding of involvement
      of 17q11. the loss of chromosome 22, and the absence of a t(X:18)(p11.2:q11.2),
      which characterizes synovial sarcoma allowed us to the final diagnosis of
      malignant peripheral nerve sheath tumour. CONCLUSION: MPNST of the heart can be
      diagnosed by combining morphological and immunohistochemical data. Cytogenetics
      can be useful in reaching a correct diagnosis, also by helping to rule out
      monophasic synovial sarcoma.

PMID- 9934586
TI  - Expression of c-erbB-2 oncoprotein in human thyroid tumours.
AB  - AIMS: c-erbB-2 expression has been found to be a potential marker of aggressive
      biological behaviour in some tumours, but the role played by this oncoprotein in
      the development and maintenance of thyroid tumours is still controversial.
      Therefore our objective was to determine whether c-erbB-2 was overexpressed in a
      large retrospective series of human thyroid tumours, including both from
      follicular and C-cell differentiation. METHODS AND RESULTS: We have studied 67
      thyroid tumours (10 follicular adenomas, 11 follicular carcinomas, three
      anaplastic carcinomas, 25 papillary carcinomas and 18 medullary carcinomas and 16
      metastases) by immunohistochemistry using an antigen retrieval method for
      paraffin-embedded material and a specific polyclonal antibody against the
      intracytoplasmic part of c-erbB-2 oncoprotein. There are marked differences in
      the pattern of c-erbB-2 immunoreactivity depending on the type of thyroid tumour.
      Thus, no expression of the oncoprotein has been found in follicular adenomas,
      follicular carcinomas and anaplastic carcinomas, but 52% of papillary carcinomas
      (membranous and diffuse cytoplasmic patterns) and all medullary carcinomas
      (granular cytoplasmic pattern) are immunopositive. CONCLUSIONS: Our results
      indicate that overexpression of c-erbB-2 oncoprotein is easily identifiable by
      immunohistochemistry in paraffin sections of certain thyroid tumours after
      applying an antigen retrieval method. This study suggests that c-erbB-2
      oncoprotein may play some role in disease progression in papillary and medullary
      thyroid carcinomas, but the significance of the different immunohistochemical
      patterns merits further investigations.

PMID- 9934587
TI  - Hepatic stellate cells (Ito cells) in veno-occlusive disease of the liver after
      allogeneic bone marrow transplantation.
AB  - AIMS: To evaluate the role of activated hepatic stellate cells (HSCs) in hepatic
      veno-occlusive disease (VOD) after bone marrow transcription (BMT), we studied
      the distribution and area of activated HSCs by immunohistochemistry for alpha
      smooth muscle actin (SMA). METHODS AND RESULTS: We examined the liver of seven
      autopsy cases with hepatic VOD or without VOD after allogeneic BMT and five
      autopsy cases without liver disease as a control both microscopically and
      immunohistochemically. In normal liver tissues, SMA-positive cells were observed
      around the central veins, while they were more frequently noted along the
      sinusoidal walls as well as around the central veins in liver tissues with or
      without VOD after BMT. The area of activated HSCs increased significantly in
      zones 1 and 2, and more prominently in zone 3 of the liver tissues after BMT than
      normal liver tissues, and was much larger in zone 3 of liver tissues with VOD.
      The activated HSCs were immunohistochemically negative for the regulatory
      contractile proteins (heavy caldesmon and calponin). CONCLUSIONS: These results
      indicated that the activated HSCs may play an important role in sinusoidal
      fibrosis and luminal narrowing or occlusion of the central veins in VOD after
      BMT.

PMID- 9934588
TI  - The histogenesis of large-cell gastric lymphomas.

PMID- 9934589
TI  - Partial or near total pancreatectomy for persistent neonatal hyperinsulinaemic
      hypoglycaemia: the pathologist's role.

PMID- 9934590
TI  - Pure monophasic, epithelial synovial sarcoma without a spindle cell component.

PMID- 9934591
TI  - Monoclonal plasma and Mott cells in a rectal adenoma.

PMID- 9934592
TI  - Desmoplastic cutaneous ganglioneuroma.

PMID- 9934593
TI  - Sertoli cell tumour in a boy with Peutz-Jeghers syndrome.

PMID- 9934594
TI  - Calcifying fibrous pseudotumour: first case report in the peritoneum with
      immunostaining for CD34.

PMID- 9934595
TI  - Breast carcinoma metastatic to a lymphoma: report of a case with review of
      literature.

PMID- 9934596
TI  - Modeling the dynamics of HIV-1 and CD4 and CD8 lymphocytes.

PMID- 9934597
TI  - Improving cephalogram analysis through feature subimage extraction.
AB  - An MLP with a GA was proposed to extract feature subimages containing orthodontic
      landmarks. Simulated images and cephalograms were used to investigate its
      performance in comparison with the cross-correlation method. From the results of
      simulated image containing shapes with different geometrical conditions, it was
      shown that the fault tolerance of the MLP for rotation, scaling, brightness
      variety, and other anomalous deformations is good enough to overcome the clinical
      application problems. It was also shown that the stability, accuracy, and speed
      of this proposed algorithm are very promising. Moreover, the performance of the
      MLP can be significantly improved by collecting, more "representative" false
      patterns. The GA is a good approach to speed up the process of feature subimage
      extraction based on the fitness evaluated using the MLP.

PMID- 9934598
TI  - Introduction to cochlear implants.
AB  - Cochlear implants have been very successful in restoring partial hearing to
      profoundly deaf people. Many individuals with implants are now able to
      communicate and understand speech without lip-reading, and some are able to talk
      over the phone. Children with implants can develop spoken-language skills and
      attend normal schools (i.e., schools with normal-hearing children). The greatest
      benefits with cochlear implantation have occurred in patients who (1) acquired
      speech and language before their hearing loss, and (2) have shorter duration of
      deafness. Gradual, but steady, improvements in speech production and speech
      perception have also occurred in prelingually deafened adults or children.

PMID- 9934599
TI  - Software for 3-D visualization/analysis of optic-disc images.

PMID- 9934600
TI  - Perceptualization of biomedical data. An experimental environment for
      visualization and sonification of brain electrical activity.

PMID- 9934601
TI  - A data-reduction process for long-term EEGs. Feature extraction through digital
      processing in a multiresolution framework.

PMID- 9934602
TI  - Exploring new instrumentation parameters for electrochemotherapy. Attacking
      tumors with bursts of biphasic pulses instead of single pulses.

PMID- 9934603
TI  - Evaluating transcutaneous oximetry data through dynamic modeling. A new method of
      measuring hypoxic tissue damage.

PMID- 9934604
TI  - Pulse analysis of patients with severe liver problems. Studying pulse spectrums
      to determine the effects on other organs.

PMID- 9934606
TI  - Description of shapes in CT images. The usefulness of time-series modeling
      techniques for identifying organs.
AB  - An attempt has been made to investigate the usefulness of AR and CAR modeling
      techniques for shape description of substructures in CT images. The efficacy of
      the models have been checked using two organ shapes (liver and kidney) obtained
      from abdominal CT sections at nearly identical locations. The contours of the
      substructures representing the shapes, along with the sequence of coordinates,
      have been obtained by using edge detection followed by an edge-linking technique,
      where maximum and minimum lengths of the edge segments could be varied. The
      modeling techniques thus applied have resulted in feature vectors of the organ
      shapes corresponding to these models. Validity of the models has been assessed on
      the basis of lower values and consistency of Euclidean distances within a class,
      as well as the differences of these values with other classes.

PMID- 9934605
TI  - Preferential direction and symmetry of electric conduction of human meridians.
      Bilaterally symmetrical acupoints provide better conductance for a better
      "connection".

PMID- 9934607
TI  - From muscle twitches to sustained (tetanic) contraction: the discovery of du Bois
      Reymond.

PMID- 9934608
TI  - What do the words of a patent mean?

PMID- 9934609
TI  - Human exposure to electric and magnetic fields from RF sealers and dielectric
      heaters--a COMAR technical information statement.
AB  - Radio frequency (RF) sealers and dielectric heaters, operating between 3 and 100
      MHz, are used for a variety of industrial applications. There is concern about
      the safety of such devices because measurements during operation often show
      leakage of electric and magnetic fields, as well as induced currents in the body,
      that exceed RF exposure guidelines. Both the leakage of fields and the absorption
      of RF energy by an operator can be reduced by shielding, proper grounding of the
      sealers, isolation of the operator from ground, and increasing the distance
      between the sealer and the operator. Several national and international standards
      now include limits on body-to-ground and contact currents for humans. Based on
      present knowledge of the biological effects of RF fields and the reported
      exposures from such devices, COMAR recommends that the leakage field strengths
      from RF sealers and dielectric heaters, as well as body-to-ground and contact
      currents, be monitored and exposure to workers be limited so as to meet the
      recommended RF exposure guidelines.

PMID- 9934610
TI  - The impact of vessel and catheter position on the measurement accuracy in
      catheter-based quantitative coronary angiography.
AB  - BACKGROUND: The calculation of absolute artery dimensions in quantitative
      coronary angiography is usually carried out by catheter calibration. It is based
      on the proportional comparison of the dimension of the imaged artery segment to
      the dimension of the imaged angiographic catheter of known size. This calibration
      method presumes an identical radiographic magnification between angiographic
      catheter and artery segment of interest. However, due to the different
      intrathoracic location of both objects the radiographic magnification or
      calibration factor is often not identical for a given angiographic projection.
      The aim of this study was to quantify the magnification error (out-of-plane
      magnification error) for the major coronary artery segments imaged in frequently
      used angiographic projections. METHODS: The intrathoracic spatial location of 468
      coronary segments (RCA 196, LAD 156, LCX 116) and their respective coronary
      catheters were established with biplane angiography and known imaging geometry
      data. The error in the radiographic magnification or calibration factor was then
      calculated for all 936 monoplane projections using the spatial coordinates and
      imaging geometry data. RESULTS: The mean magnitude of magnification error was 4%
      within all 936 measurements. The magnitude and direction of error varied with the
      lesion localization and the angiographic projection angle (range -12.6% to
      +10.6%). The error characteristics could be described with six typical error
      groups by stratifying the data according to the three main coronaries and two
      angiographic planes. In 24% of measurements, the magnification error exceeded the
      5.2% error limit acceptable for reference vessel sizing. Measurements of left
      coronary arteries were mainly affected by it. CONCLUSION: The magnification error
      contributes to the calibration error in measuring arterial dimensions by
      quantitative angiography. This error may affect the reliability of clinical
      studies and the proper sizing of interventional devices. These findings could be
      used to improve current error correction algorithms in order to reduce the effect
      of the magnification error in measuring arterial dimensions.

PMID- 9934611
TI  - Different left ventricular relaxation parameters in isolated working rat and
      guinea pig hearts. Influence of preload, afterload, temperature, and
      isoprenaline.
AB  - In isolated ejecting rat and guinea pig hearts, the sensitivity of the time
      constant tau of left ventricular isovolumic pressure fall, the maximum pressure
      fall velocity min LVdP/dt, and the relaxation time to different hemodynamic
      conditions, temperature, and isoprenaline were investigated. Tau was obtained by
      fitting the isovolumic pressure fall three-parametrically to the exponential p(t)
      = p infinity + (p0-p infinity) exp (-t/tau) which was found to be superior to
      semilogarithmic estimation. The influence of different working conditions on the
      relaxation parameters was tested by a rank correlation test and quantified by
      calculating standardized regression coefficients. Hemodynamic conditions were
      altered by changing left ventricular end-diastolic pressure (increasing inflow to
      the heart) and peak pressure (max LVP, varying aortic outflow resistance), and by
      atrial pacing (variation of interbeat interval). Lusitropic sensitivity was
      investigated by changing temperature and by applying isoprenaline. All regression
      parameters were only moderately sensitive to changes in end-diastolic pressure,
      max LVP, or heart rate, with the exception of a considerable afterload dependence
      of min LVdP/dt in rat hearts. This dependence, however, can be overcome to a
      large extent by dividing min LVdP/dt by mean aortic pressure. Isoprenaline
      strongly influenced all relaxation parameters, and so did temperature, except for
      relaxation time in guinea pig hearts. We conclude that tau serves as a reliable
      relaxation parameter, also in the hearts of small animals with heart rates up to
      450 beats/min. In isolated hearts, min LVdP/dt, corrected for afterload
      dependence, is also suitable as a complementary index of the early relaxation
      phase.

PMID- 9934612
TI  - Tissue Doppler imaging and the quantification of myocardial function.
AB  - Tissue Doppler imaging (TDI) has recently been introduced in clinical
      echocardiography. Most widely used are tissue velocity maps, in which the
      velocity of moving tissue is calculated relative to the transducer from the
      Doppler shift and displayed as colour-encoded velocity maps in either M-mode or
      two-dimensional image formats (Doppler velocity mode). This allows detection and
      quantification of dyssynergic areas of the myocardium. Additionally, the
      velocities may be studied with pulsed wave-tissue Doppler sampling (PW-TDS) which
      displays the velocity of a selected myocardial region versus time with high
      temporal resolution. Less often used, are tissue acceleration maps which display
      acceleration or velocity change of subsequent frames as different colours
      (Doppler acceleration mode). These maps may find application in clinical
      electrophysiology. Another TDI modality is tissue energy imaging, which is based
      on the integration of the power spectrum of the Doppler signals from the tissue.
      This technique provides maps of Doppler energy which are represented as colour
      brightness. Such maps offer potential for the study of myocardial perfusion. TDI
      modalities have promise to become clinically useful for quantifying myocardial
      function.

PMID- 9934613
TI  - Impact of presence of abnormal wall motion on echocardiographic determination of
      left ventricular function with automated boundary detection technique: re
      evaluation.
AB  - It is still unclear whether echocardiography with an automated boundary detection
      technique (ABD) can accurately determine the left ventricular (LV) volume and
      function particularly in the presence of LV wall asynergy. We intended to re
      evaluate the reliability and application of the ABD, which was based on the
      acoustic quantification technique (Sonos 2500, Hewlett Packard) for the LV volume
      measurement in patients without or with LV wall asynergy. A total of 80 patients
      (mean age 56 years) who underwent left ventriculography (LVG) were divided into
      two groups. The group A consisted of 29 patients with normal LV wall motion and
      the group B consisted of 51 patients with generalized or regional LV wall motion
      abnormality. In group A patients, the LV end-diastolic volume (LVEDV) was 96 +/-
      25 ml by ABD and 112 +/- 33 ml by LVG and those of LV end-systolic volume (LVESV)
      were 44 +/- 14 ml by ABD and 48 +/- 17 ml by LVG, thus resulting in the
      underestimation of LV volume by 12% in average. Under these conditions, the LV
      ejection fraction (LVEF) by ABD, 54 +/- 8%, correlated well with that by LVG, 58
      +/- 7%. Although underestimation of LV volume by 17% in average also occurred in
      groups B (N.S.), LVEF was found to correlate well with that by LVG; 27 +/- 8% vs
      30 +/- 11% (r = 0.87, SEE = 3.1%) for 21 patients with the generalized LV
      asynergy; 39 +/- 10% vs 39 +/- 12% (r = 0.86. SEE = 3.3%) for 30 patients with
      the regional LV asynergy. These results demonstrate the feasibility of the ABD in
      determining the LVEF, although underestimation can occur in measuring the
      absolute LV volume in patients with or without LV asynergy.

PMID- 9934614
TI  - The role of early measurement of nitrogen-13 ammonia uptake for predicting
      contractile recovery after acute myocardial infarction.
AB  - Previous studies have shown that the maintenance of cell membrane integrity and
      metabolism requires the persistence of residual myocardial blood flow. The
      purpose of this study was to assess the role of N-13 ammonia positron emission
      tomographic (PET) imaging performed early after an acute myocardial infarction
      for predicting functional recovery. Seventeen patients with an acute myocardial
      infarction were included in the study. Thirteen received thrombolytic therapy, 2
      underwent immediate angioplasty of the infarct-related artery and 2 were treated
      with heparin. N-13 ammonia imaging was performed 6 +/- 2 days after the acute
      event and was followed by elective angioplasty in 13 patients. Using a 16-segment
      polar map display, regional N-13 ammonia uptake was expressed as a percentage of
      maximal segmental uptake and classified as normal (> 63%), moderately reduced (63
      50%) and severely reduced (< 50%) based on values of tracer uptake obtained from
      healthy subjects. By echocardiographic assessment of regional wall thickening
      within 96 hours and at 1 month after the infarct, we examined the relationship
      between blood flow and functional outcome of myocardial segments in the infarct
      related area. Regional wall thickening was graded on a 4-point scale: normal (1),
      hypokinesia (2), akinesia (3) and dyskinesia (4). Of 77 dyssynergic segments at
      baseline echocardiographic study, 43 had normal flow, 15 moderately reduced flow
      and 19 severely reduced flow. Segments with N-13 ammonia uptake > or = 50%
      demonstrated a significant improvement in wall thickening score at follow-up (p <
      0.001), whereas segments with N-13 ammonia uptake < 50% showed no improvement in
      wall thickening scores (p < 0.001). The proportion of segments improving
      contractility by at least 1 score was significantly higher in the group of
      segments with N-13 ammonia uptake > 63%. The predictive value for defining
      functional recovery with segmental N-13 ammonia uptake > 63% was 86%. The
      predictive value for absence of recovery (uptake < 50%) was 54%. In conclusion,
      our data showed that early after an acute myocardial infarction N-13 ammonia
      imaging provides information regarding functional outcome.

PMID- 9934615
TI  - An echocardiographic and magnetic resonance imaging comparative study of right
      ventricular volume determination.
AB  - Assessment of right ventricular volume and function is important in many clinical
      settings involving heart or lung disease. However, the complexity of the right
      ventricular anatomy has prevented accurate volume determination by two
      dimensional echocardiography. In the present study, 5 models incorporating
      standard echocardiographic views, were used to determine right ventricular volume
      in 10 human subjects. Two models were contingent on the true crescentic
      appearance of the right ventricle, whereas the remaining 3 calculated the right
      ventricular volume as a pyramid, an ellipsoid or other tapering geometrical
      figures, respectively. Subsequently, echocardiographic right ventricular volumes
      were compared to magnetic resonance imaging derived volumes. Correlation analysis
      and agreement measurement between the echocardiographic and magnetic resonance
      end-diastolic volume were performed in 10 out of 10 subjects and in 9 out of 10
      subjects for the end-systolic volume. The 2 crescentic models resulted in the
      most reliable estimation of right ventricular volume. Those findings suggest that
      models based on right ventricular anatomical landmarks are feasible and should be
      preferred in echocardiographic studies.

PMID- 9934616
TI  - Diagnosis of cardiac abnormalities in patients with nonischemic tachyarrhythmias:
      additional value of MR imaging.
AB  - PURPOSE: To assess the contribution of cardiac magnetic resonance (MR) imaging in
      the evaluation of patients with nonischemic tachyarrhythmias and equivocal
      diagnosis following echocardiography and cardiac angiography. METHODS AND
      RESULTS: Twenty-five patients with nonischemic tachyarrhythmias and equivocal
      diagnosis were studied using MR imaging. Before the MR examination all patients
      underwent two-dimensional echocardiography and cardiac catheterization. The type
      of additional information, obtained with MR imaging, ranged from confirming a
      suspected diagnosis in 5 patients (20%) to the identification of new important
      anatomic or functional information, allowing a correct diagnosis in 18 patients
      (72%). In two patients (8%) the MR diagnosis was incomplete. CONCLUSION: MR
      imaging may be an important additional diagnostic tool in the evaluation of
      cardiac abnormalities in patients with nonischemic tachyarrhythmias.

PMID- 9934617
TI  - Bilateral electrodermal activity: relationships to state and trait
      characteristics of hemisphere asymmetry.
AB  - Influences of trait and state characteristics of individual brain lateralization
      on bilateral electrodermal activity (EDA) were examined. EDA was observed in two
      different recording conditions: (1) non-specific skin conductance responses
      (ns.SCRs) were obtained during a stimulus-free recording period of 5 min; and (2)
      stimulus evoked skin conductance responses (SCRs) were elicited by 80
      dichotically presented pairs of pure tones which--at the same time--constituted
      the items of a test to estimate subject's lateral ear dominance. In addition to
      ear dominance, degree of right-handedness and hemispheric preference, i.e.
      preferred direction of conjugate lateral eye movements (CLEMs) were assessed as
      trait-like characteristics of individual laterality. With respect to asymmetry of
      ns.SCRs, no effects of the laterality variables were observed. Analysis of SCRs,
      however, resulted in significant interactions of ear dominance and hemispheric
      preference with degree of right-handedness indicating higher SCR amplitudes on
      the hand contralateral to the preferred hemisphere in strong dextrals. Weak right
      handers showed a different pattern of bilateral asymmetries, partly in the
      opposite direction. Additionally, phasic effects of cortical asymmetry on SCRs
      seem to be modified by trait characteristics of individual laterality. Results
      underline the importance of precisely controlling degree of handedness in studies
      of bilateral electrodermal activity. Furthermore, the observed effects support
      the assumption of cortical influences on EDA, but argue against the existence of
      a single cortical mechanism modulating asymmetries in the electrodermal system.

PMID- 9934618
TI  - Early gamma response is sensory in origin: a conclusion based on cross-comparison
      of results from multiple experimental paradigms.
AB  - The study investigates the functional correlates of the early, time-locked gamma
      response. The study utilized a unique experimental strategy which involved the
      utilization of a series of experimental paradigms to which all subjects (n = 20)
      were exposed to in the same recording session. These paradigms induced an
      increasingly complex configuration of processes for their respective task
      performance and also required different levels of attention allocation. In their
      order of administration, the paradigms were single stimulus (SS), mismatch
      negativity (MMN), evoked potential (EP), easy oddball (OB-EZ) and hard oddball
      (OB-HD). Auditory stimuli were used in the study (10 ms r/f time, 50 ms duration,
      65 dB SPL) with the standards as 1000 Hz or 1900 Hz and deviants as 2000 Hz. The
      early gamma showed a frontocentral topography. The difference between Fz and Pz
      recording sites were statistically significant. A comparative analysis of the
      gamma responses showed that the gamma that was obtained at the early time-window
      of 0-150 ms as a time-locked activity occurred irrespective of experimental
      paradigm; the early gamma did not vary with the degree of task complexity or with
      attentional allocation. It was concluded from these findings that the early gamma
      is basically a sensory phenomenon. Various studies have previously shown that
      under perceptual/cognitive tasks, gamma response is obtained as a non-phase
      locked activity in the late time-windows. These studies concluded that the gamma
      response is basically perceptual/cognitive in function. However, in these studies
      the early sensory gamma was also present in the data. Collectively taken, these
      findings may lead to the conclusion that the gamma response is a multifunctional
      phenomenon, with the early portion representing sensory and the late portion
      perceptual/cognitive processing.

PMID- 9934619
TI  - Topographic differences in CNV amplitude reflect different preparatory processes.
AB  - Topographic differences in Contingent Negative Variation (CNV) were recorded
      while people were preparing for cognitive versus motor tasks in an S1-S2
      paradigm. CNV had a frontal distribution when people prepared to encode words
      into long-term memory, whereas CNV was more centrally distributed when the tasks
      were predominantly motoric. These topographic differences appeared to be related
      to the type of task rather than the amount of information extracted from the S2,
      because a direct manipulation of the level of S2 processing had little effect on
      CNV amplitude. The topographic differences in CNV suggest that preparation for
      motor activity is a different psychological process from preparation for stimulus
      processing and that these two processes are subserved by different neural
      structures. This experiment also demonstrated that a recognition memory paradigm
      can be useful in the investigation of the psychological correlates of CNV.

PMID- 9934620
TI  - Effects of distracting stimuli on CNV amplitude and reaction time.
AB  - The present study investigated the reliability of CNV distraction and rebound
      effects, and their relation with reaction time. Twenty-four subjects were
      presented three blocks of trials: (1) a control block--a fixed foreperiod
      reaction time task consisting of a flash-tone-key press sequence; (2) a divided
      attention block--randomly intermixed trials with and without a short-term memory
      task (three visually-presented letters) in the S1-S2 interval (50% of each); and
      (3) a second control block. In trials with the short-term memory task, subjects
      recalled the letters after the key press to the tone. Compared to the control
      block, CNV amplitudes during trials with letters were significantly smaller and
      reaction times to S2 were significantly slower (distraction effect). In contrast,
      CNV amplitudes during trials with no-letters were significantly larger (CNV
      rebound), but the reaction times were again significantly slower. This
      dissociation of CNV rebound and reaction time could provide an objective
      neurophysiological tool to probe attention functions in both normal and clinical
      populations.

PMID- 9934621
TI  - Decrement of the N1 auditory event-related potential with stimulus repetition:
      habituation vs. refractoriness.
AB  - We examined whether the amplitude decrement traditionally found for the N1 peak
      of the event-related potential (ERP) with repetition of auditory stimuli results
      from the process of habituation or from the refractory period of the neural
      elements underlying the N1 response. These competing accounts of the process
      underlying the N1 decrement with repetition differ in terms of the predicted
      effects of variations in stimulus repetition and interstimulus interval (ISI).
      These predictions were examined using a short-term habituation design with a
      factorial combination of stimulus repetition and ISI. Forty-five subjects
      received 21 stimulus trains, each consisting of seven innocuous tones, all at 1
      kHz except the sixth, which was a 1.5-kHz tone. Each subject was assigned to one
      of three ISI conditions (either 1, 3 or 10 s). The results provide little support
      for the view that N1 response decrement with stimulus repetition reflects a
      process of habituation. The present results provide greater support for the view
      that this decrement is based on the separate refractory periods or recovery cycle
      processes of at least two neural generators contributing to activity in the N1
      peak latency range.

PMID- 9934622
TI  - The relationship between salivary secretory immunoglobulin A and cortisol:
      neuroendocrine response to awakening and the diurnal cycle.
AB  - The level of secretory immunoglobulin A (sIgA) measured in saliva is
      downregulated during periods of chronic stress. In contrast, the response to an
      acute stress challenge is a transient increase. The process of awakening is
      associated with stress neuroendocrine activation characterised by increases in
      salivary cortisol. We therefore examined if this period of hypothalamic-pituitary
      adrenal (HPA) activation was associated with changes in salivary sIgA.
      Associations of sIgA with the diurnal cortisol cycle were also investigated in a
      separate study. The awakening cortisol response was measured in 30 healthy day
      active young adults. There was a marked elevation from the first awakening level
      over the succeeding 30 min. SIgA showed the opposite response with a marked fall
      from the highest first awakening concentration in the same samples over the same
      period. The cortisol rise was significantly correlated with the sIgA fall (r =
      0.42). Salivary sIgA showed a similar diurnal cycle to cortisol in a study on
      eight healthy young adults. An early morning acrophase was followed by a decline
      to a stable base some 6 h after awakening. The physiological significance of
      these relationships and possible implications for vulnerability to infection are
      discussed.

PMID- 9934624
TI  - Comparison of two EEG asymmetry indices in depressed patients vs. normal
      controls.
AB  - In 11 non-depressed, age-matched controls, and in 13 depressed patients, we
      compared the frontal alpha asymmetry mean for a baseline session with the
      percentage of the time in the session when the asymmetry score > 0. It was found
      that the percent index was a better discriminator of the two groups than was the
      asymmetry score.

PMID- 9934623
TI  - Attention to features of separate objects: an ERP study of target-shooters and
      control participants.
AB  - In a visual discrimination task stimuli consisted of a color circle and a grating
      pattern, i.e. target features were distributed between two objects. The relation
      (hierarchical vs. parallel) between the attentional processing of the task
      related features (color and spatial frequency) was investigated by using the
      methods of event-related potentials (ERPs). Participants with considerable
      practice in visual attention (target shooters; n = 13) were compared to control
      subjects (n = 11). Attention-related ERP components, i.e. selection (anterior)
      positivity (SP), selection negativity (SN), N2 (N2b), furthermore the late
      positivity (P3b) emerged only if the circle had relevant color. These results
      suggest preponderance of color processing. Target shooters were faster and more
      accurate than the control group. Attention-related components (SP, N2b) and the
      late positivity (P3b) were larger in shooters, but the relations among the
      attention-related components were the same in two groups, showing similar
      progression of the target selection process.

PMID- 9934625
TI  - Synthesis of cholesterol esterase by monocyte-derived macrophages: a potential
      role in the biodegradation of poly(urethane)s.
AB  - Many studies have described the role of monocyte-derived macrophages (MDM) in
      inflammation leading to atherosclerosis, a process in which alterations in the
      metabolism of cholesterol esters is well established. On the other hand, the
      mechanism of MDM activation in response to biomaterial surfaces is still not well
      understood. Several studies have described the different degrees of activation of
      monocytes on poly(urethane) surfaces by measuring the release of early markers of
      differentiation, such as cytokines. It has been possible to decrease MDM
      activation in contact with materials by modifying the material surface with
      antioxidants. Therefore, it has been proposed that it is the reactive oxygen
      species provided by MDM which are responsible for deleterious effects observed in
      material-derived inflammation. A recent study has shown that one of the markers
      of the degree of differentiation of MDM is the synthesis of cholesterol esterase
      (CE), an enzyme demonstrated as causing biodegradation of polyester(urethane)s
      and more recently polyether- and polycarbonate-poly(urethane)s as well. In this
      review article, markers used to assess MDM differentiation on material surfaces
      will be described and related to the activation of MDM. In particular, the CE
      accumulation in MDM which is associated with atherosclerosis will be related to
      its degradative potential during chronic inflammation. How this may impact on the
      biostability of implanted poly(urethane) medical devices is discussed.

PMID- 9934626
TI  - In vitro antimicrobial activity of a new antiseptic central venous catheter.
AB  - A central venous catheter coated with a new antiseptic combination, silver
      chloride (AgCl) and benzalkonium chloride (BKC) in a polymer matrix, was
      developed. The antimicrobial efficacy and the ability to prevent surface
      colonization, after elution in both serum and saline, were evaluated and compared
      to catheters coated with silver sulfadiazine/chlorhexidine. The results of in
      vitro assays demonstrated that the AgCl-BKC coated catheters had a broad spectrum
      of activity against bacteria and C. albicans and prolonged antimicrobial activity
      for extraction periods of up to 30 days. These data suggest that AgCl-BKC coated
      catheters may provide another solution for reduction of catheter-related
      infections.

PMID- 9934627
TI  - Assessment of hemodialysis access performance by color-flow Doppler ultrasound.
AB  - Hemodialysis access failure is a major cause of morbidity for patients with end
      stage renal disease with costs in excess of $743 million annually. Color-flow
      doppler ultrasound is the only mobile noninvasive technique that provides direct
      visual imaging of the access and measurement of access flow. Doppler ultrasound
      can identify patients at increased risk of future thrombosis and allow preventive
      intervention. Prospective trials show that ultrasound-based access management
      programs can decrease thrombosis rates, prolong access longevity, and decrease
      the cost of hemodialysis access management. It should be included as part of a
      coordinated program of hemodialysis management.

PMID- 9934628
TI  - Reduction of calcification by various treatments in cardiac valves.
AB  - The importance of glutaraldehyde pretreated bioprosthetic heart valves fabricated
      from bovine pericardium or porcine aortic valves is well realized in the
      management of valvular heart diseases. But, calcification limits the durability
      and is the most frequent cause of failure of these bioprosthetic heart valves.
      Various research groups in the world are actively involved in describing,
      understanding, and preventing calcification of bioprosthetic heart valves. Since
      there is no satisfactory clinical means for preventing or treating this disorder,
      attempts are made to improve the anticalcification properties of the replacement
      valves in the preparation stage itself. Research in this area is very active, and
      many newer approaches are made to mitigate the problem. An attempt has been made
      in the present article to review various theories put forward to explain the
      causative factors involved and mechanistic aspects of biocalcification and to
      present various strategies attempted for the prevention of calcification with the
      special feature on the work done in the area in our laboratory.

PMID- 9934629
TI  - An introduction to the biostatistical technique of resampling.
AB  - This article will introduce resampling method to burn injury researchers and care
      givers. With the use of a data set taken from a published burn injury research
      project, this technique is extensively described and fully illustrated in a
      stepwise fashion by tables and figures. The recent exponential growth in the use
      of this method has produced a concurrent need to understand its fundamentals.
      Researchers, reviewers, and care givers will need to be familiar with resampling
      to evaluate the published results of various studies. Additionally, as burn
      research continues to focus on the molecular and cellular aspects of injury and
      healing, data analysis by resampling might prove to be a useful adjunct to
      standard biostatistical methods. Many useful links on the Internet (starting at
      www.statistics.com) can be followed for further readings, software, and
      tutorials.

PMID- 9934630
TI  - Postburn vitamin C infusions do not alter early postburn edema formation.
AB  - To determine whether vitamin C would alter burn induced edema accumulation, hind
      paw venous pressure, lymph flow (QL), and lymph-to-plasma protein ratio (CL/CP)
      were monitored in groups of 5 dogs before and 4 hours after 1) a 5 sec 100
      degrees C or 90 degrees C foot paw scald; 2) intravenous vitamin C given 30 min
      before or after a 100 degrees C scald; and 3) vitamin C given 30 min after a 90
      degrees C scald. Throughout the experiments, hind paw venous pressure was
      elevated and maintained by outflow restriction until steady state QL and
      (CL/CP)min were reached. Changes in protein permeability (CL/CP), fluid
      conductance properties (Kf) of the capillary membrane, and paw weight gain were
      determined. Compared with preburn values, scald uniformly produced significant (P
      < .05, ANOVA) increases in QL, CL/CP and Kf. Although preburn infusion of vitamin
      C significantly (P < .01) attenuated burn-induced increases in paw weight gain
      (36 +/- 3% vs 19 +/- 4%), neither of the groups that received vitamin C postburn
      experienced significant modulations in paw weight gain (28 +/- 4% vs 36 +/- 3% in
      100 degrees C burn only; 23 +/- 4% vs 28 +/- 3% in 90 degrees C burn only) or in
      any of the variables used to monitor capillary membrane integrity. Vitamin C
      infusions initiated after graded scald produced no changes in the burn-induced
      increases in microvascular permeability or in edema formation measured at the
      injury site.

PMID- 9934631
TI  - Use of subatmospheric pressure to prevent progression of partial-thickness burns
      in a swine model.
AB  - The poorly understood, complex series of events that follows thermal injury
      frequently results in progressive loss of tissue. The concept of reversing this
      distinctive series of events has focused on the zone of stasis. Tissues in the
      zone of stasis that surround burn injuries usually die over a period of 48 to 72
      hours postinjury, resulting in a more severe injury. Application of a controlled
      subatmospheric pressure (125 mm Hg) in an artificially closed space to partial
      thickness burns in pigs significantly decreased the maximum depth of cellular
      death under the burn when the pressure was applied within 12 hours after burn
      creation (depth of control burns = 0.885 +/- 0.115 mm; subatmospheric pressure
      treated burns (0-hour delay) = 0.095 +/- 0.025 mm). A decrease in the depth of
      cell death was noted when subatmospheric pressure was applied for as little as 6
      hours. In summary, the application of the negative pressure to partial-thickness
      burn injuries prevented progression of the wound to a deeper injury in this
      experimental pig model. A 12-hour working window exists between injury and
      treatment with reduced pressure, with an application time of as little as 6 hours
      for successful prevention of injury progression. This technique may represent a
      new, inexpensive, 'low tech' method for the treatment of partial-thickness burn
      injuries.

PMID- 9934632
TI  - Self-inflicted burn injuries.
AB  - Self-inflicted burns are uncommon yet disturbing. A 9-year retrospective review
      of all admissions to the Mercy Hospital of Pittsburgh Burn Center from 1987 to
      1995 found 11 out of 1135 patients to have self-inflicted burns. Ten of these
      patients had a psychiatric diagnosis prior to injury: major depression in 6
      cases, schizophrenia in 3 cases, and a personality disorder in 1 case. The other
      patient was diagnosed with major depression during her hospitalization. Escape
      from stress/sadness was the motive for 6 patients. Two were actually attempting
      suicide and 2 were motivated by hallucinations/delusions. On the basis of this
      review, we recommend that patients with an abnormal psychological profile-
      including suicidal ideation--be adequately monitored and regularly followed by
      appropriate mental health professionals. It is hoped that an awareness of the
      phenomena of self-destruction by burning will prevent these injuries in the
      future.

PMID- 9934633
TI  - Development and solution of finite-difference equations for burn injury with
      spreadsheet software.
AB  - This article presents a brief description of a set of equations by which the
      thermal burn process may be modeled, a formulation of the differential equations
      into a finite-difference format, and a simple method of solution using a standard
      commercial spreadsheet software application. A companion article provides a
      discussion of results that can be obtained with the modeling techniques presented
      here. A short version of the spreadsheet program is available from the author.

PMID- 9934634
TI  - Topical sulfamylon reduces engraftment of cultured skin substitutes on athymic
      mice.
AB  - Sulfamylon (mafenide acetate) remains extremely valuable for the control of the
      bacterial contamination of burn wounds, but it is cytotoxic to cultured
      keratinocytes used for wound closure. Because composite skin substitutes develop
      a partial epidermal barrier in vitro, they may hypothetically tolerate the use of
      topical Sulfamylon. To test this hypothesis, cultured skin substitutes were
      prepared from cultured human fibroblasts; keratinocytes were attached to these
      collagen-based substrates, which were grafted to full-thickness wounds in athymic
      mice (n = 8 per group). Wounds were irrigated twice daily with 5% (wt/vol)
      Sulfamylon solution or with a formulation of noncytotoxic antimicrobials (0%
      Sulfamylon). On day 9 after grafting, the wounds were treated with dry dressings
      and assessed at 4 weeks for expression of human leukocyte antigens-A, B, C and at
      2, 3, and 4 weeks for percentage of original wound area and surface electrical
      capacitance in picofarads (pF). Data were analyzed for statistical significance
      (P < .05) by Fisher's exact test, Student's t test, and repeated measures
      analysis of variance: [table: see text] The data demonstrate that irrigation of
      cultured skin substitutes with a solution of 5% Sulfamylon results in smaller
      wound area, fewer wounds that contain human cells, and greater surface hydration
      (higher surface electrical capacitance) than irrigation with noncytotoxic
      antimicrobial agents. These results support the conclusion that cultured skin
      substitutes of this type do not tolerate the chemical toxicity of Sulfamylon as
      well as skin autografts. Further improvements in the properties of the epidermal
      barrier of cultured skin substitutes may facilitate the use of Sulfamylon or
      other potent antimicrobial agents for the management of microbial contamination
      during engraftment of transplanted skin cells.

PMID- 9934635
TI  - Thermal injury-induced enhancement of oxidative metabolism by mononuclear
      phagocytes.
AB  - C57BL/6 female mice were subjected to full-thickness scald thermal injuries
      covering 25% of their total body surface areas, and thioglycollate-elicited
      peritoneal macrophages were isolated 4 days later. Macrophages from burned mice
      displayed a 2-fold increase in phorbol ester-stimulated superoxide production,
      whereas superoxide production in response to zymosan or immune complexes was
      unaltered. Maximal levels of superoxide production by thermal injury macrophages
      were comparable for all stimuli. Reduction of injury size to 12.5% total body
      surface area abrogated the enhancement of superoxide production. Protein kinase C
      activity and protein phosphorylation was not altered after thermal injury. These
      results indicate that the enhancement of macrophage-oxidative metabolism after
      thermal injury is independent of changes in reduced nicotinamide adenine
      dinucleotide phosphate oxidase or protein kinase C activity and may in part
      explain the increased susceptibility to multiple organ failure after this form of
      trauma.

PMID- 9934636
TI  - Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas
      aeruginosa infection of burned mice.
AB  - Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that causes
      severe infections in patients with burns. The P aeruginosa regulatory gene, lasR,
      regulates the expression of several virulence factors. The specific lasR isogenic
      mutant, PAO-R1, is defective in the synthesis of the 2 elastases (LasB and LasA)
      and produces low levels of exotoxin A and alkaline proteases. In this study, we
      used a burned mouse model to examine the role of lasR in the pathogenesis of P
      aeruginosa infections. We have examined the following aspects of P aeruginosa
      infections: 1) lethality to the burned mouse, 2) the dissemination within the
      body of the burned mouse, and 3) the local spread within the burned skin. In
      comparison with its parent strain, PAO1, PAO-R1 was less lethal. In addition, the
      numbers of PAO-R1 microorganisms recovered from the livers and spleens of the
      burned mice were less than those of PAO1. Furthermore, at 8 hours postinfection,
      equivalent numbers of PAO1 and PAO-R1 were detected at the inoculation site of
      the burned skin. However, only PAO1 microorganisms were detected at other sites
      of the burned skin. These results suggest that the lasR gene contributes
      (directly and indirectly) to the dissemination of P aeruginosa within the body of
      burned mice and its horizontal spread within the burned skin.

PMID- 9934637
TI  - An unusual cause of burn injury: unsupervised use of drugs that contain
      psoralens.
AB  - Although psoralens are useful components of the psoralen ultraviolet A-range
      therapy that is mainly used for the treatment of vitiligo, psoriasis, and
      hypopigmented scars, they have a narrow margin of safety. Oral and topical forms
      of psoralen-containing drugs are routinely used in medicine. Because psoralens
      sensitize skin to ultraviolet A light, phototoxic reactions are the most frequent
      adverse effect of this treatment. Sunburn may sometimes be a major injury in
      psoralen users because high doses or inappropriate use of the drug may render the
      skin extremely sensitive. In this article, we present the case of a vitiligo
      patient who was admitted to our facility with an intense burn after the topical
      use of 8-methoxypsoralen solution as a suntanning agent. We will also discuss the
      unusual nature of this type of burn and the course of phototoxic lesions and
      their differences from a typical sunburn.

PMID- 9934638
TI  - Scar assessment: current problems and future solutions.
AB  - Current problems in the assessment of scars are discussed. The concept of
      subjective and objective aspects of scar assessment is introduced. The patient's
      own view of the scar (the subjective component) can currently be assessed and may
      be very influential in determining the patient's quality of life, irrespective of
      the actual physical characteristics of the scar. The objective aspects of the
      scar, including size, shape, texture, and pliability, are currently difficult to
      measure. Although the Vancouver Scar Scale has been used as the standard for
      objective measurements, there are problems with both the validity and reliability
      of this instrument. Various imaging techniques may permit more reliable and
      accurate methods for measuring the quantitative aspects of scars.

PMID- 9934639
TI  - Burn therapy of years ago.

PMID- 9934640
TI  - When one is two.
AB  - This article is about Karen, who was 20 weeks pregnant when she was involved in a
      gas explosion. The explosion caused a 35% body surface area deep partial
      thickness burn to her legs and arms. This article focuses on the most important
      concerns and fears Karen expressed while she was in our care. Her statements
      triggered various clinical memories from several nurses in the burn unit, and
      thus the stories unfold. These stories reflect nursing practice through the
      psychological care, clinical signs, and pathophysiology of our patient. The
      spoken stories, coupled with the reflective stories, provide a total picture of
      the multidimensional care nurses provide for their patients.

PMID- 9934641
TI  - Cost reduction strategies in burn nutrition services: adjustments in dietary
      treatment of patients with hyponatremia and hypophosphatemia.
AB  - Two clinically effective adjustments in diet therapy were tested at a burn center
      as strategies to lower clinical care costs. The use of adult enteral formulas for
      pediatric burn patients reduced the incidence of hyponatremia and the need for
      costly sodium supplements. The prophylactic administration of oral phosphate
      during the first days of hospitalization may lessen the decline in serum
      phosphate and save costs for the treatment of hypophosphatemia of severely burned
      patients.

PMID- 9934642
TI  - The gas fireplace: a new burn hazard in the home.
AB  - Gas fireplaces have become popular in recent years. This article presents the
      first reported case of a burn injury from contact with the glass front of a gas
      fireplace. An investigation of the surface temperature of the glass fronts of gas
      fireplaces was undertaken to clarify the risks posed by these units. Surface
      temperature measurements of the glass fronts of 3 common gas fireplace models
      were obtained using a thermocouple probe. Glass temperatures reached 200 degrees
      C within 6.5 minutes of ignition, climbing to 245 degrees C at 14 minutes after
      ignition. Glass temperature continued to rise beyond this point, but it could not
      be monitored because the adhesives securing the thermocouple probe melted. Glass
      temperatures of 50 degrees C were recorded at 30 minutes after the unit was shut
      off. The temperatures of the glass fronts of glass fireplaces are sufficient to
      cause cutaneous burns within seconds of contact both while the fireplace is in
      use and up to one half hour after it has been turned off. Current industry safety
      standards are not directed at the prevention of contact burns. We recommend that
      (1) mechanical guards be installed to create a barrier in front of the glass; (2)
      strict warning labels be applied to the units and ignition switches; and (3) burn
      prevention information be distributed with the owner's manual for these products.

PMID- 9934644
TI  - The first report of the National Screening Committee.

PMID- 9934643
TI  - Return to school as an outcome measure after a burn injury.
AB  - Outcome measures have become an important tool to assist with monitoring the
      efficacy of burn care. One such measurement for children is the time required for
      them to return to school, as well as their behavior and academic performance in
      school after a burn injury. The purpose of this study was to relate demographic
      data with return-to-school time and school performance. Through medical record
      review and interviews with patients, parents, and school teachers, information
      was obtained regarding the patient's burn injury, as well as home and school
      status before and after the burn injury. School information before the burn
      injury was obtained after patient admission. Schools were contacted 6 months
      after hospital discharge for data after the burn injury. Thirty-four patients
      aged 6 to 16 years had their outcomes evaluated from September 1993 to June 1995.
      Average total body surface area burned was 25.9%; the mean area of full-thickness
      burn was 17.5%. Length of stay averaged 30.8 days. Sixty-five percent of patients
      were discharged with splints, and all were discharged with a pressure program.
      Children returned to school an average of 7.4 days after discharge, and the
      average number of missed school days was 22. Thirty-four percent of the children
      had a school reentry visit, and either a phone call, written material, or both
      were provided in lieu of a visit to the other schools. For this population, burn
      injury did not appear to impact outcome negatively as it related to a child's
      return or function in school. These children returned to school rather rapidly
      after discharge and functioned as well or better after injury. Little loss of
      grade was noted, and only those children with problems in school before the burn
      injury had problems after the burn injury. Contact with the child's school before
      reentry might have assisted with the smooth transition.

PMID- 9934645
TI  - Antenatal screening for HIV in the UK: what is to be done?

PMID- 9934646
TI  - Natural history of Down's syndrome: a brief review for those involved in
      antenatal screening.

PMID- 9934647
TI  - Acceptance of amniocentesis by women in the state of Montana (USA) who are screen
      positive for Down's syndrome.
AB  - OBJECTIVE: To assess factors influencing uptake of amniocentesis after a positive
      Down's syndrome screening result. METHODS: Interviews of 53 Montana women with
      screening risks > or = 1 in 300 after delivery. RESULTS: Thirty had accepted
      amniocentesis ("yes" group) and 23 had declined ("no" group) (57% uptake). Age at
      delivery was significantly higher (p = 0.02) for the "no" than the "yes" group
      (mean 35.3 nu 31.7 years). The mean risk of Down's syndrome ascertained by
      screening was 1 in 190 for the "no" group and 1 in 115 for the "yes" group (p =
      0.05). Statistically significant differences (p < or = 0.05) between opinions in
      the two groups included: (a) desire to know if the fetus had Down's syndrome; (b)
      perception of the burden of care for an affected child; (c) support of doctor,
      spouse, and relatives for choice about amniocentesis; (d) attitudes toward
      abortion; (e) importance of religion; and (f) concerns about the amniocentesis
      procedure. The most important factor for those choosing amniocentesis was knowing
      if the fetus had Down's syndrome, and for those not choosing amniocentesis,
      attitude about abortion. CONCLUSION: Our results show the need for prescreening
      education to enable pregnant women to make informed decisions about screening for
      Down's syndrome and diagnostic testing.

PMID- 9934648
TI  - Obstacles to timely neonatal screening in North Thames.
AB  - OBJECTIVE: To assess the timeliness of neonatal (Guthrie card) screening in North
      Thames, and to identify the most effective ways of improving it. DESIGN: Analysis
      of information routinely collected in the course of neonatal screening;
      reanalysis of published data on blood phenylalanine concentration in
      phenylketonuria (PKU) over the first two weeks; simulation studies on the impact
      of different interventions. SUBJECTS: 100,690 infants born over one year and
      screened at Great Ormond Street Hospital NHS Trust. OUTCOME MEASURE: Interval
      between birth and reading PKU screen results. RESULTS: Although 75% of samples
      (district range 55-91%) were collected by day 7, only 81% had arrived in the
      laboratory seven days later (range 57-96%). The average interval between birth
      and reading results was 14.5 days, with only 9.7% read by day 10. Samples could
      be collected from day 4 without significant impact on false negative rates for
      PKU. If samples were collected from day 4 and posted promptly (second class), the
      average interval between birth and reading results could be reduced to 9.3 days.
      If first class mail were used and the laboratory operated on Saturdays, and used
      assays that could be read the same day rather than bacterial inhibition assays,
      the average would be 7.8 days, with 96% read by day 10. CONCLUSION: Timeliness of
      neonatal screening shows unacceptable variation between districts, and delays in
      dispatch of specimens to the laboratory. Same day, first class posting should be
      introduced, and samples could be collected between days 4 and 8.

PMID- 9934649
TI  - Planning for a possible national colorectal cancer screening programme.
AB  - This report presents the planning, projected costs, and manpower requirements for
      a possible national colorectal cancer screening programme. Screening would be
      offered to all those aged 50-69, who comprise 20% of the United Kingdom
      population. The initial screening test would be faecal occult blood testing every
      two years. A local programme, administered by a screening centre serving a
      population of one million, would be responsible for inviting 100,000 subjects a
      year. The response rate in Nottingham, the UK trial centre, was below 60%. Good
      informed compliance would require the active support of primary care. The
      invitation and test kit would be sent by post, and completed tests returned to
      the screening centre, for reading and reporting. Those with a positive initial
      screen (about 2%) would be recalled for assessment. This would result in 60,000
      investigations each year across England and Wales, given a screening uptake rate
      of 60%. Clearly any deviation from this predicted rate would have a major effect
      on resources. Assessment and any subsequent treatment would be by a
      multidisciplinary team working at the cancer unit, as recommended in recent NHS
      executive guidance. The best method for investigation is colonoscopy. When
      completed successfully this allows visualisation of the whole bowel. However,
      performance varies widely across the UK, and there is insufficient skilled
      manpower to undertake this additional workload. Most significantly the technique
      has a mortality rate of 0.02%, so the programme might expect 12 deaths a year,
      which would not be acceptable. Alternatively, assessment of screen positive cases
      could be by a combination of double contrast barium enema and flexible
      sigmoidoscopy, with a comparable sensitivity. Both procedures have much lower
      morbidity and mortality rates. Colonoscopy would then only be required for a
      smaller number of patients, with cancer or suspicious lesions, or after
      unsatisfactory investigations. Quality assurance should be an integral part of
      the programme, as in the other NHS cancer screening programmes, involving all
      professional groups and coordinated by a regional quality assurance reference
      centre. Cost estimates are over 40 million Pound a year, together with any
      allowance for general practitioners, with additional capital and training costs
      at the start of the programme. Given a 60% overall uptake rate, a test
      sensitivity of 60%, and a recall rate of 2%, about 35% of the cases of colorectal
      cancer in the eligible population--that is, about 5400 cases, could be detected
      each year. As this would also depend on maintaining good compliance, a continuing
      value of 4000 cases is more realistic. Appreciable savings on costs of treatment
      are unlikely as aggressive curative treatments would be expensive.

PMID- 9934650
TI  - A comparison of cancer detection rates achieved by breast cancer screening
      programmes by number of readers, for one and two view mammography: results from
      the UK National Health Service breast screening programme.
AB  - OBJECTIVE: To determine the increased cancer detection rate, if any, of
      programmes in the UK National Health Service breast screening programme (NHSBSP)
      using more than single reading of mammograms. DESIGN: Information on the
      detection of cancers by individual screening programmes from annual (KC62)
      returns, supplemented by questionnaire information about the number of readers.
      SETTING: The 87 NHSBSP programmes from England and Wales for the screening year 1
      April 1996 to 31 March 1997. The study includes all programmes for prevalent
      screens where two views are mandatory, but excludes the four programmes using two
      view mammography for incident screening. MAIN OUTCOME MEASURES: Cancer detection,
      invasive cancer detection, and small (< 15 mm) invasive cancer detection by
      mammographic reading protocol using single reading as the reference level.
      RESULTS: Programmes collectively using single reading detected the lowest rate of
      cancers at both prevalent (first) and incident (subsequent) screening. The
      highest rate of age standardised cancer detection was achieved by programmes
      using double reading with arbitration. At prevalent screens, where all programmes
      used two views, those programmes using double reading with arbitration detected
      32% (95% confidence interval (CI) 3% to 69%) more small (< 15 mm) invasive
      cancers than programmes using single reading. At incident screens, where all
      programmes analysed used one view this increased to 73% (95% CI 40% to 113%).
      Recall rates showed no obvious difference between single reading and the double
      reading protocols, being around 7% for prevalent screens and 3.5% for incident
      screens. DISCUSSION: The results suggest that the increase in cancer detection
      resulting from increasing the number of readers depends on the number of views,
      and is higher for one view than two views. Single reading of one view results in
      a low detection rate of small invasive cancers for most individual programmes. It
      is, however, recognised that a small number of individual readers may achieve
      high detection rates with such a protocol. All groups of programmes using
      different reader/view protocols are on average close to or above target cancer
      detection rates, except those using single reading of one view (mediolateral
      oblique) at incident screens.

PMID- 9934651
TI  - Methodological issues in mammography double reading studies.
AB  - OBJECTIVES: An examination of the methods used in assessing cancer detection
      rates in double reading studies to obtain a clear interpretation of the disparate
      results from differing studies. SETTING: National breast screening programmes.
      METHODS: Critical appraisal of methodologies used in the comparison of cancer
      detection rates with single or double reading. RESULTS: The reported improvement
      in cancer detection rate with double reading varies greatly between studies,
      depending upon whether the study is blinded and the statistic used. A method of
      calculating the increase in cancer detection rate due to a second reader is
      proposed.

PMID- 9934652
TI  - Mammographic parenchymal patterns and mode of detection: implications for the
      breast screening programme.
AB  - OBJECTIVES: To assess the effects of mammographic parenchymal patterns on the
      risk of breast cancer detected at first screen, second screen, and in the
      interval between these two screens. SETTINGS: A nested case-control study within
      a screening cohort in East Anglia was designed. The study group comprised 502
      patients with cancer at the prevalence screening round, 198 patients with
      interval cancer, and 175 with cancer at the first incidence screen. These
      patients were matched with 2601 controls. METHODS: The mammographic parenchymal
      patterns of breast tissue were assessed according to Wolfe's classification.
      Statistical analysis was by conditional logistic regression. RESULTS: Overall,
      67% of patients and 59% of controls were considered to have high risk pattern (P2
      + DY) mammogram. The risk associated with P2 or DY mammographic patterns compared
      with N1 was higher for interval cancers (odds ratios (ORs) 2.2 and 2.4
      respectively) than for screen detected cancers (ORs 1.7 and 1.1 respectively).
      For interval cancers in the first 18 months after the last negative mammogram,
      the risk was particularly high (ORs 3.8 for P2 and 4.1 for DY compared with N1).
      The high risk associated with P2 and DY patterns was concentrated on invasive
      ductal grade III cancers (ORs 2.7 and 3.8) rather than grade I or II cancers (ORs
      1.6 and 1.2). CONCLUSIONS: The study strongly suggests that screening
      effectiveness is reduced for high risk parenchymal patterns which are associated
      with high grade cancers. Changes should aim at improving screening sensitivity
      for dense parenchymal patterns, and the diagnosis of high grade tumours.

PMID- 9934653
TI  - Birth prevalence of Down's syndrome in England and Wales 1990 to 1997.

PMID- 9934654
TI  - Performance of antenatal HIV screening strategies in the UK: correction.

PMID- 9934655
TI  - Clinical evidence and multiple models: new responsibilities.

PMID- 9934656
TI  - The new American psychoanalysis: a commentary.

PMID- 9934657
TI  - "Traveling affectively alone": a personal derailment in analytic listening.
AB  - Questioning whether or not we have entered a new "two-person" paradigm, the
      author shares a traumatic personal experience, considers its impact on her work
      with a patient, and discusses some clinical and epistemological dilemmas in self
      disclosure.

PMID- 9934658
TI  - The "unobjectionable" positive countertransference.
AB  - Even though Freud said that "the secret of therapy is to cure through love," the
      "unobjectionable" positive countertransference has remained a neglected topic in
      clinical and theoretical writings. This paper explores a number of personal and
      historical reasons to account for this avoidance. A case vignette is presented to
      highlight the facilitating and therapeutic role of the positive
      countertransference. It also demonstrates the analyst's struggles with his loving
      feelings and some of the reasons behind this conflict. The case is then used to
      explore the functions that the positive countertransference serves for the
      analysand, the analyst, and the analytic process. In conclusion, a number of
      questions are posed for an emerging model of psychoanalytic technique that would
      encompass the analyst's noninterpretive contributions to the process.

PMID- 9934659
TI  - Neutrality, abstinence, and the therapeutic alliance.
AB  - Concepts of neutrality and abstinence are discussed in terms of the variant
      opinions about them, pro and con, with particular reference to efforts to
      dispense with them based on the unavoidable role of the analyst's personal
      influence and subjectivity in the analytic process. Stereotypes of both
      neutrality and abstinence are examined, and the therapeutic alliance established
      as the most appropriate context within which to articulate the essential and
      constructive role of effective analytic neutrality and abstinence. The alliance
      is not possible without the persistent exercise of both neutrality and
      abstinence; conversely, other components of the alliance are intended to
      facilitate and preserve neutrality and abstinence on the part of both analyst and
      analysand. These elements are essential factors in effective analytic practice.

PMID- 9934660
TI  - Where the action is: the enacted dimension of analytic process.
AB  - Enacted processes--variously addressed in the current literature by such terms as
      enactment, actualization, and interaction--represent the conceptual reuniting of
      Freud's concepts of transference and acting out. These various concepts include a
      recognition that transference may be represented not only on the verbally
      symbolized level but also on the enacted level, through psychic organizations and
      processes that use behavior, silence, and even speech as symbolic vehicles.
      Countertransference too finds representation within the enacted realm, in
      response to and in concert with the patient's enacted processes, though in more
      attenuated fashion. Enacted transference-countertransference processes are
      conceptualized as a continuously evolving second dimension of analytic treatment.
      This enacted dimension of analytic process exists alongside, and inextricably
      interwoven with, the treatment's verbal content, with characteristics unique to
      each analytic dyad. It occurs naturally and inevitably, without conscious
      awareness or intent, and is outside the domain of explicit technical
      interventions. The observable outcroppings or end points of processes within the
      enacted dimension are what are currently referred to as enactments. Attention to
      these unintended but meaningful and often elaborately developed characteristics
      of the treatment process furthers our understanding of the therapeutic action of
      psychoanalysis. The process of integrating the enacted with the verbal dimension
      of treatment enables the analysand to achieve higher levels of psychic
      organization.

PMID- 9934661
TI  - Perverse defenses in neurotic patients.
AB  - Distinguishing perverse defenses from the concept of obligatory perversion allows
      perverse defenses to be examined in neurotic patients. Perverse defenses against
      reality, one's conflicts, and relationships with others are connected with affect
      intolerance, difficulty with analytic collaboration, and analytic impasse.
      Perverse defenses, including the cultivation of states of distraction,
      excitement, and pomposity, as well as perverse sadomasochistic relations with
      others, protect against the unbearable: intense affects, painful ideas, and
      loving, committed need of a valued, distinct person. Patients' perverse,
      vindictive refusal to be reasonable provokes perverse countertransference
      reactions whereby the analyst stands in judgmentally and critically for the
      seemingly absent demands of reason, morality, and analytic progress.

PMID- 9934662
TI  - A new analytic dyad: homosexual analyst, heterosexual patient.
AB  - The paradoxical thesis is presented that the extraordinary aspect of the analytic
      experience of a homosexual male analyst and his heterosexual male analysand is
      that it was ordinary, that the fundamental processes of transference,
      countertransference, and analysis of defense and resistance were determinative.
      The unique variations of these processes with this particular patient are
      explored. The patient entered treatment unaware of the analyst's homosexuality,
      which he discovered during the analysis. The course of this discovery, its
      transformations, its defensive uses, its transference meanings, and its fate in
      the termination are delineated. Through viewing the patient's reactions to the
      analyst's homosexuality as potential entry points to the transference, the
      analytic process was enhanced and facilitated.

PMID- 9934663
TI  - Telephone analysis: out of sight, but not out of mind.
AB  - Past traditions and prejudices may have precluded many analysts from openly
      considering the use of telephone analysis as a viable treatment option. However,
      at times psychoanalysis by telephone may represent the best treatment available
      for a particular patient. Use of the telephone in clinical practice evokes
      complex feelings and raises a number of important issues for both patient and
      analyst. A case of telephone analysis is presented to illustrate the poignancy of
      initial telephone contact, issues associated with the decision to do
      psychoanalysis by telephone, some of the paradoxes and complexities of telephone
      work itself, and the termination process. Initial resistances by both patient and
      analyst are discussed, and modification of technique and its applicability to
      psychoanalysis in general are examined. Indicators for telephone analysis are
      considered.

PMID- 9934664
TI  - Lay analysis in the postwar years.

PMID- 9934665
TI  - Reflecting our past--looking toward our future.

PMID- 9934666
TI  - Grappling with global concerns in the search for an HIV vaccine.
AB  - There is a need for increasing international collaboration in the search for a
      safe and effective HIV vaccine. In addition to the ethical issues that must be
      considered in conducting any clinical research, unique issues arise in vaccine
      research and in international research. Careful deliberation and guideline
      development regarding the ethics of international vaccine research was the focus
      of a series of recent consultations sponsored by Joint United Nations Programme
      on HIV/AIDS (UNAIDS) around the world.

PMID- 9934667
TI  - Stress and HIV disease progression: psychoneuroimmunological framework.
AB  - Psychoneuroimmunology (PNI) is the study of the interrelationships among
      behavior, neural and endocrine function, and the immune system. PNI investigates
      the relationships among stress, physiological dysregulation, and health outcomes.
      Research has supported the theory that emotional distress and the resultant
      neuroendocrine activation can induce immune system suppression. This suppression
      has significant implications for disease susceptibility and progression. HIV
      disease and its extensive immunological consequences are explored within this
      framework. Potential physiological pathways that may mediate stress-induced
      dysregulation within the context of HIV disease are identified. Key HIV-related
      PNI research studies are reviewed and critically analyzed. Implications for
      nursing practice and research are discussed.

PMID- 9934668
TI  - Patient appraisal of mandarin orange didanosine: implications for adherence and
      well-being.
AB  - Didanosine (Videx, ddI) has been shown to be an effective agent in the treatment
      of HIV disease. However, patients have had difficulties adhering to didanosine
      preparations due to taste aversion and/or associated nausea. The efficacy of
      didanosine may, therefore, be compromised. This is of concern to clinicians who
      seek to promote patient adherence to medication regimes and to foster the quality
      of patient well-being. In this study, focus groups were used to gather
      exploratory data about patient (n = 15) response to the new mandarin orange
      didanosine preparation. Data were audiotaped, transcribed verbatim, and
      systematically analyzed by the investigators using inductive techniques. Findings
      provide information regarding client evaluation of the new didanosine preparation
      and patterns of usage. Although clients generally find the mandarin orange
      preparation more tolerable, they describe engaging in numerous strategies aimed
      at attenuating what they experience as the inconvenience of taking the
      medication. Mental tricks, systematic restructuring of daily routines and
      environment, and dietary schemes were among the strategies devised by patients
      through trial and error to self-promote their adherence.

PMID- 9934669
TI  - Spirituality, psychological well-being, and HIV symptoms for African Americans
      living with HIV disease.
AB  - The purpose of this descriptive cross-sectional study was to explore the
      contribution of spiritual well-being and human immunodeficiency virus (HIV)
      symptoms to psychological well-being measured by depression, hope, and state
      trait anxiety in a sample of 117 African-American men and women with a mean age
      of 38 years living with HIV disease. Of the respondents, 26% had acquired
      immunodeficiency syndrome (AIDS), and 74% were HIV seropositive. Each participant
      completed a sociodemographic questionnaire, the Sign and Symptom Checklist for
      Persons with HIV Disease, the Spiritual Well-Being Scale, the Nowotny Hope Scale,
      State-Trait Inventory, and the Beck Depression Inventory. The findings suggest
      that existential well-being, a spiritual indicator of meaning and purpose, more
      than religious well-being, was significantly related to the participants'
      psychological well-being. In addition, HIV symptoms were found to be significant
      predictors of psychological well-being. These findings support the need for
      nurses to continue exploring ways to integrate and support spirituality within
      the domains of clinical practice.

PMID- 9934670
TI  - Women and the prevention of HIV infection: an integrative review of the
      literature.
AB  - In the United States, recent epidemiological evidence suggests that the epidemic
      of AIDS is growing rapidly among women. However, the theories used to guide
      research in the area of prevention of HIV infection often do not account for
      gender. As a result, research with women has been limited and the development of
      interventions to reduce risk behaviors impeded. This review examines research
      with women and HIV related to prevention and identifies the gaps and strengths in
      this body of work. Content analysis was used to evaluate 40 published papers
      meeting the following criteria: title or abstract indicating a report of research
      with women and HIV/AIDS, refereed journal as source, English language, and
      implications for prevention of HIV among women. Findings suggest a growing
      awareness of women's risk of HIV, but basic research pertaining to the behavior
      of women related to their vulnerability to HIV infection is scant. Prevention
      research and evaluation of interventions are also in their infancy. This review
      calls attention to the need for continued research that specifically addresses
      women's needs in the prevention of HIV.

PMID- 9934671
TI  - Management of occupational exposures to HIV: updated guidelines for postexposure
      prophylaxis. Centers of Disease Control and Prevention.

PMID- 9934672
TI  - Designing a short-term process evaluation of a wellness center serving persons
      with HIV/AIDS.

PMID- 9934673
TI  - Human immunodeficiency virus type 2.

PMID- 9934674
TI  - New study shows average per patient cost of HIV care in managed care setting
      stabilized in 1997.

PMID- 9934675
TI  - Molecular analysis of ovine prion protein identifies similarities between BSE and
      an experimental isolate of natural scrapie, CH1641.
AB  - New variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy
      (BSE) are caused by the same strain of pathogen and, as sheep can develop
      experimental BSE, this has raised concern that humans may be at risk from eating
      mutton if BSE has naturally transmitted to sheep. Biochemical typing of abnormal
      prion proteins (PrPsc) has been suggested to detect BSE in sheep. Although this
      approach is ingenuous, we can now report biochemical evidence of strain variation
      in contemporary and archival brain tissue from cases of experimental BSE or
      experimental and natural scrapie in sheep. Interestingly, we found at least one
      isolate of natural scrapie (CH 1641) with a very similar, but not identical,
      PrPsc profile to BSE but which differs from BSE in its transmission
      characteristics to mice.

PMID- 9934676
TI  - Scrapie strain-specific interactions with endogenous murine leukaemia virus.
AB  - The finding that a senescence-accelerated mouse (SAMP8) shows early brain ageing,
      with histopathological changes resembling those seen in scrapie, combined with
      the discovery of high levels of endogenous murine leukaemia virus (MuLV) in
      brains of SAMP8 mice prompted us to examine the effect of scrapie infection on
      MuLV titres in this strain and in one of its progenitors, the AKR strain. Three
      scrapie strains (ME7, 22L and 139A) that had a comparatively short incubation
      period in SAMP8 and AKR mice caused an increase in brain MuLV titres that was
      scrapie strain-specific: in each mouse strain, the greatest effect was with 1
      39A, and the least with ME7. The 22A scrapie strain, which has a long incubation
      period in SAMP8 mice, did not affect MuLV titres in brains of this mouse strain.
      Previous analyses of scrapie incubation periods in AKR, SAMP8 and another strain
      derived from an AKR cross (SAMR1) showed an inverse relationship between brain
      MuLV titres and scrapie incubation periods. This finding, combined with the
      effect of scrapie on MuLV titres, suggests an interaction between the scrapie
      infectious process and MuLV replication.

PMID- 9934677
TI  - Protease-resistant prion protein produced in vitro lacks detectable infectivity.
AB  - The 'protein-only' hypothesis of prion propagation argues that infectious prions
      consist of PrP(Sc), a conformational isomer of host-derived prion protein
      (PrP(C)), which can be distinguished from PrP(C) by its partial resistance to
      proteases. While protease-resistant PrP has been produced by mixing PrP(Sc) and
      recombinant-derived PrP(C) in vitro, bioassay of any new infectivity has been
      precluded by the need to use a large molar excess of same species PrP(Sc).
      Transgenic mice expressing a chimaeric hamster-mouse PrPC (MH2M PrP(C)) are,
      unlike conventional mice, highly susceptible to Sc237 hamster scrapie. In
      addition, they produce MH2M PrP(Sc) and infectivity which is pathogenic for
      conventional mice. We have therefore attempted to produce MH2M PrP(Sc) in vitro
      as any infectivity produced could be distinguished from the hamster PrP(Sc) used
      to promote the conversion by bioassay in conventional mice. Although protease
      resistant MH2M PrP was produced, no infectivity was detected on bioassay. These
      results argue that acquisition of protease resistance by PrP(C) is not sufficient
      for the propagation of infectivity.

PMID- 9934678
TI  - Construction and characterization of murine neuroblastoma cell clones allowing
      inducible and high expression of the prion protein.
AB  - A tetracycline-inducible expression system has been established for the prion
      protein (PrP) in murine neuroblastoma cells (N2a). For this purpose, N2a cells
      were first stably transfected with either the tetracycline-controlled
      transactivator or the reverse transactivator. After selection of N2a clones which
      carried one of these transactivators, the murine PrP gene (Prnp) was introduced
      under the control of the transactivator-responsive promoter in a second round of
      stable transfection. Stably double-transfected N2a clones carrying the reverse
      type but not the normal transactivator were found to be fully inducible, giving a
      low background of Prnp expression before induction and high expression after
      induction. Stably double-transfected N2a cells were at least as productive as N2a
      cells over-expressing Prnp permanently under the control of a strong viral
      promoter. Furthermore, the selected N2a clones allowed the Prnp expression level
      to be quantitatively controlled by varying the level of the effector substance,
      the tetracycline-derivative doxycycline. The clones were fully controllable, as
      over-expression could be switched on and off as desired. These N2a clones may
      become an important tool for elucidation of the cellular function of PrP and may
      pave the way for the tetracycline-inducible expression of many genes in this
      neuroblastoma cell line.

PMID- 9934679
TI  - The bovine papillomavirus type 4 long control region contains an epithelial
      specific enhancer.
AB  - Bovine papillomavirus type 4 (BPV-4) is a mucosal epitheliotropic virus that is a
      causative agent in alimentary carcinoma of cattle. The long control region (LCR)
      of this virus controls expression of the transforming proteins, E8 and E7.
      Deletion mutants of the LCR were prepared and assayed for their ability to
      activate transcription from the LCR promoter in primary bovine palate
      keratinocytes (the natural target cell for BPV-4) and fibroblasts. The LCR was at
      least an order of magnitude more active in keratinocytes than in fibroblasts. An
      epithelial specific enhancer was identified that activated transcription from the
      SV40 promoter to levels identical to the full-length LCR. One of the active sites
      in the enhancer is 100% conserved in the LCR of human papillomavirus type 16. The
      results demonstrate that the BPV-4 LCR has an epithelial specific enhancer, which
      offers the opportunity to study epithelial specific transcriptional regulation of
      papillomavirus promoters.

PMID- 9934680
TI  - The E2 protein of human papillomavirus type 16 is translated from a variety of
      differentially spliced polycistronic mRNAs.
AB  - The major regulation protein of human papillomavirus (HPV) transcription is the
      viral E2 protein. Previous studies have identified a variety of alternatively
      spliced mRNAs containing multiple open reading frames (ORFs) encoding the E2
      protein of HPV type 16. In these mRNAs the E2 ORF is contained as an internal
      ORF. In the present study, the translational capacities of three mRNA species
      starting at the p97 promoter and containing the 880/2581, 880/2708 and 226/2708
      splice junctions upstream of the E2 ORF were investigated. Partial cDNAs spanning
      the E2 ORF and the related upstream ORFs were synthesized and assessed for E2
      protein translation in vivo, in COS cells, and in vitro, in cell-free systems.
      Results of these analyses indicated that E2 protein was translated from all three
      mRNAs. Translation efficiency of E2 from the natural polycistronic templates was
      lower compared with that from a synthetic monocistronic control. Translation from
      the d-type bicistronic template (226/2708) was more efficient than that from the
      a-type (880/2708) and a'-type (880/2561) polycistronic templates. Further
      investigation of the translation of proteins encoded by the ORFs preceding the E2
      ORF showed that a- and a'-type templates served for translation mainly of E7 but
      also of E61, while the d-type template served for translation of E6IV. Overall,
      the translation data support the suggestion that the corresponding mRNAs may
      function as polycistronic transcripts.

PMID- 9934681
TI  - The major capsid protein, VP1, of human JC virus expressed in Escherichia coli is
      able to self-assemble into a capsid-like particle and deliver exogenous DNA into
      human kidney cells.
AB  - The full-length major capsid protein, VP1, of the human polyomavirus JC virus was
      cloned and expressed in Escherichia coli. VP1 protein expressed in E. coli self
      assembled into capsid-like particles and caused haemagglutination of human O-type
      red blood cells. Caesium chloride density-gradient centrifugation analysis
      revealed that the capsid-like particles consisted of virion-like pseudovirion and
      empty capsid-like pseudocapsid populations. The morphology of pseudo-virion and
      pseudocapsid particles was observed under the electron microscope. The
      pseudovirions contained DNA and RNA molecules but the pseudocapsids did not
      contain any nucleic acid, as analysed by DNA extraction. DNA-binding activity of
      VP1 was also demonstrated by the South-Western probing method in vitro.
      Furthermore, pseudocapsids were able to deliver exogenous DNA into human foetal
      kidney epithelial cells. These results indicate that recombinant JC virus VP1 is
      able to self-assemble into capsid-like particles and to package DNA in the
      absence of the minor capsid proteins, VP2 and VP3. This prokaryotic assembly
      system may facilitate the investigation of maturation mechanism(s) of
      polyomaviruses. Furthermore, capsid-like particles of JC virus VP1 generated in
      E. coli potentially could be used as a human gene transfer vector.

PMID- 9934682
TI  - Adenovirus core protein VII displays a linear epitope conserved in a range of
      human adenoviruses.
AB  - A monoclonal antibody (MAb) which recognized a linear epitope on polypeptide VII
      of human adenovirus (Ad) serotype 4 also interacted with polypeptides VII of Ad
      serotypes 2, 5, 7 and 10, but not with 12 and 40, in Western blotting. Utilizing
      a hexapeptide phage display library, the MAb was found to recognize the consensus
      sequence RXYXPX. A peptide based on a similar sequence from Ad2, viz.
      VEEARNYTPTPPPV, was synthesized and shown to inhibit binding of the MAb to
      polypeptide VII. Direct sequencing of the Ad4 polypeptide VII gene validated
      these observations, the sequence RNYTPA being detected. Comparison with gene
      sequences from other Ads indicates that this sequence is preserved in polypeptide
      VII of types 2 and 5 but in types 12 and 40 insertion of another residue disrupts
      this motif.

PMID- 9934683
TI  - US3 protein kinase of herpes simplex virus type 2 plays a role in protecting
      corneal epithelial cells from apoptosis in infected mice.
AB  - To clarify the biological role of US3 protein kinase of herpes simplex virus type
      2 (HSV-2) in vivo, the expression of the viral antigen, the appearance of
      apoptotic bodies and DNA fragmentation were examined immunohistologically after
      corneal infection of mice with three different kinds of HSV-2 strain 186: the
      wild-type virus, a US3-deficient mutant (L1BR1) and its revertant (L1B-11). In
      both wild-type 186- and L1B-11-infected mice, viral antigen was diffusely found
      in the corneal epithelium; no apoptotic changes were detected in the epithelial
      cells. Whereas, in L1BR1-infected mice, HSV-immunoreactivity was localized around
      the virus-inoculated sites, and a large number of apoptotic bodies were observed
      in the corneal epithelium with dual-positive reactions for both HSV
      immunostaining and TUNEL staining. These results suggest that the US3 protein
      kinase plays an important role in protecting HSV-2-infected cells from apoptotic
      death in vivo.

PMID- 9934684
TI  - Bovine herpesvirus 1 requires glycoprotein H for infectivity and direct spreading
      and glycoproteins gH(W450) and gB for glycoprotein D-independent cell-to-cell
      spread.
AB  - By analogy with glycoprotein H (gH) of herpes simplex virus type 1 (HSV-1) and
      pseudorabies virus (PRV), gH may also be essential for penetration and cell-to
      cell spread of bovine herpes-virus 1 (BHV-1). This was verified with a gH
      negative BHV-1 mutant (gH-BHV-1), which replicated normally on gH-expressing
      cells but was unable to form plaques and infectious progeny on non-complementing
      cells. The block in entry could be overcome by polyethylene glycol-induced
      membrane fusion, demonstrating that gH is not essential for egress. Propagation
      of gH-BHV-1 on cell lines expressing wild-type gH or gH(W450), which complements
      the function of BHV-1 gD for cell-to-cell spread, indicated that gH(W450) is more
      efficient than wild-type gH in mediating direct spread of BHV-1. This was
      supported by the plaque sizes induced by rescued gH-BHV-1 that expressed wild
      type gH and gH(W450). Infection of cell lines expressing gH of BHV-1, HSV-1 and
      PRV with gH-BHV-1, HSV-1 and PRV mutants demonstrated that heterologous gH
      molecules could not complement gH function in penetration or cell-to-cell spread.

PMID- 9934685
TI  - Biphasic translocation of a 70 kDa heat shock protein in human cytomegalovirus
      infected cells.
AB  - Human cytomegalovirus (HCMV) reportedly induces the expression of a 70 kDa heat
      shock protein (hsp70) with no known function in the virus replication cycle. We
      report here a remarkably specific translocation pattern of hsp70 during HCMV
      infection of human diploid fibroblasts. Immunofluorescent observation and Western
      blotting of subcellular fractions revealed nuclear localization of hsp70 early in
      infection and predominantly cytoplasmic localization of hsp70 late in infection.
      Treatment of HCMV-infected cells with cycloheximide followed by treatment with
      actinomycin D allowed virus immediate-early gene expression but inhibited hsp70
      nuclear localization. Phosphonoacetic acid and tunicamycin, both of which
      reportedly inhibit HCMV DNA replication, did not inhibit HCMV-induced nuclear
      localization of hsp70 but inhibited hsp70 translocation from the nucleus to the
      cytoplasm. These results indicate a correlation between HCMV multiplication and
      hsp70 localization, suggesting that hsp70 may play a role in HCMV multiplication.

PMID- 9934686
TI  - Identification of transactivator and nuclear localization domains in the Epstein
      Barr virus DNA polymerase accessory protein, BMRF1.
AB  - The Epstein-Barr virus (EBV) BMRF1 gene product is an essential component of the
      viral DNA polymerase and is absolutely required for lytic virus replication. In
      addition to its polymerase accessory protein function, we recently demonstrated
      that BMRF1 is a transactivator, inducing expression of the essential oriLyt
      promoter, BHLF1. However, the regions of BMRF1 required for transactivation of
      BHLF1 are unknown. Here we demonstrate that the carboxy-terminal portion of the
      BMRF1 protein (amino acids 378404), although not required for DNA binding or
      polymerase processivity function, is required for transactivator function as well
      as nuclear localization. Site-directed mutagenesis of this region allowed us to
      separate the transactivator and nuclear localization motifs of BMRF1. The two DNA
      binding domains of BMRF1 are also required for efficient transactivation of the
      BHLF1 promoter.

PMID- 9934687
TI  - Analysis of murine gammaherpesvirus-68 transcription during lytic and latent
      infection.
AB  - Murine gammaherpesvirus-68 (MHV-68) is a gamma2-herpesvirus that upon
      experimental infection of laboratory mice establishes a latent infection in B
      lymphocytes. To date, no virus-encoded gene products have been reported to be
      expressed during latent infection. In this study, viral transcription has been
      analysed in a persistently infected B-cell line and abundant and preferential
      transcription of open reading frame M3 has been identified. Significantly, in
      situ hybridization analysis of latently infected mouse spleens with probes
      corresponding to 20 MHV-68 ORFs demonstrated active transcription of a single
      ORF, corresponding to M3. The kinetics and pattern of transcription of M3 were
      compared with that of the virally encoded tRNAs (vtRNAs), previously demonstrated
      to constitute a marker for latent infection in the spleen. Transcription of
      vtRNAs in splenic tissue could be first detected at 7 days post-inoculation
      (p.i.) in scattered cells in periarteriolar lymphoid sheaths (PALS). At 10 days
      p.i., vtRNA transcription was widespread and localized not only to cells in PALS
      but also to cells within developing germinal centres and from 21 days p.i.
      expression was detected exclusively within lymphoid follicles. Transcription of
      vtRNAs could be detected as late as 70 days p.i. In contrast, the histological
      localization of M3 transcription, which was first detected at 7 days p.i. in
      scattered cells in PALS, never changed and transcription could not be detected
      beyond 21 days p.i. These results suggest that M3 is an ORF that is expressed
      early during the establishment of latency in vivo.

PMID- 9934688
TI  - Induction of human herpesvirus-8 DNA replication and transcription by butyrate
      and TPA in BCBL-1 cells.
AB  - Human herpesvirus-8 (HHV-8) is a gammaherpesvirus that is present primarily in a
      state of low level persistence in primary effusion lymphoma cell lines. Using
      BCBL-1 cells that harbour HHV-8 but lack Epstein-Barr virus, we demonstrate that
      sodium butyrate is much more effective than the phorbol ester 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) at inducing high levels of class II and III virus
      transcription and viral DNA replication, but also initiates apoptosis. Apoptosis
      occurs prior to assembly of virions when high concentrations of butyrate (1-3 mM)
      are used, whereas reduction of butyrate concentration to 0.3 mM decreases the
      rate of apoptosis and results in production and secretion of enveloped virions
      that are visualized at high number by electron microscopy in approximately 20% of
      BCBL-1 cells. Butyrate induces much higher levels of multiple class II and class
      III transcripts than does TPA, including v-MIPI, v-IL-6, v-Bcl-2, vGPCR and
      ORF26. A decrease in concentration of butyrate from 3 to 0.3 mM delays the peak
      induction of these genes, but peak levels remain higher than peak levels in
      response to TPA. These studies indicate that the massive apoptosis induced by 3
      mM butyrate could be diminished and delayed by reduction of butyrate
      concentration to 0.3 mM, thereby allowing expression of high levels of lytic
      associated genes and production of high yields of HHV-8 virions.

PMID- 9934689
TI  - Localization of isoprenylated antigen of hepatitis delta virus by anti-farnesyl
      antibodies.
AB  - Hepatitis delta virus (HDV) is a subviral pathogen that requires pre-existing or
      concurrent infection with hepatitis B virus (HBV). HDV expresses two forms of a
      single protein, the delta antigen (HDAg), which are identical except for an
      additional 19 residues at the C terminus of the large form. Within this C
      terminal extension a cysteine residue is isoprenylated; this isoprenylation is
      critical for interaction with HBV envelope proteins to enable virus assembly and
      release into the medium. Therefore, large HDAg must be recruited to an
      extracellular compartment. However, immuno-staining with HDAg-specific antibodies
      has localized the large antigen mainly to the nucleus and supports the notion
      that large HDAg suppresses virus replication in the nucleus. Since isoprenylation
      would increase the hydrophobicity of the protein and may favour transport towards
      specific membranes, the question remains whether the large HDAg detected in the
      nucleus carries an isoprenyl group. To address this issue, antibodies against the
      farnesyl modification were generated to allow direct visualization of the antigen
      by immunofluorescence microscopy. The anti-farnesyl antibodies specifically
      stained large HDAg expressed in Huh-7 cells, and the signal was largely
      restricted to the nucleus; the staining pattern could be superimposed on those of
      cells stained for large HDAg. The large HDAg translocated into the nucleus was
      therefore isoprenylated. In addition, antibodies specific for the farnesyl
      modification should be applicable to the study of other similarly isoprenylated
      proteins.

PMID- 9934690
TI  - Characterization of the major nuclear localization signal of the Borna disease
      virus phosphoprotein.
AB  - Borna disease virus (BDV) replicates and transcribes its negative-sense RNA
      genome in the nucleus. The BDV phosphoprotein (P) is localized in the nucleus of
      infected cells and cells transfected with P expression constructs. To identify
      the nuclear localization signal (NLS) of P, COS-7 cells were transfected with
      wild-type or mutant forms of P fused with green fluorescent protein (GFP).
      Whereas GFP alone was exclusively cytoplasmic, P or P-GFP were nuclear. Analysis
      of carboxy- and amino-terminal truncation mutants of P indicated that amino acids
      (aa) 20-37 are sufficient to promote efficient nuclear accumulation of the fusion
      protein. Residual nuclear import of GFP was observed with portions of P including
      aa 33-134 or aa 134-201, suggesting the presence of additional NLS motifs. The
      major NLS of P appears to be bipartite. It consists of two basic aa domains,
      R22RER25 and R30PRKIPR36, separated by four non-basic aa, S26GSP29.

PMID- 9934691
TI  - A recombinant measles virus expressing biologically active human interleukin-12.
AB  - Suppression of cell-mediated immunity (CMI) is well-documented during and after
      measles. This immunosuppression is suggested to result from decreased production
      of interleukin-12 (IL-12), a key interleukin for CMI. In an attempt to clearly
      discern the role of IL-12 in measles-induced immunosuppression, a measles virus
      (MV) that expresses biologically active human IL-12 was generated. This was
      achieved by inserting the coding sequences of the two subunits (p35 and p40) of
      human IL-12 separated by an internal ribosome entry site in an additional
      transcription unit between the H and the L genes of MV. Although the IL-12
      expressing MV grew slightly slower than the normal MV, it stably maintained the
      inserted sequences (3.2 kb) and uniformly expressed the foreign genes after 10
      passages in cell culture. These findings suggest that MV is a well-suited vector
      for delivery of proteins of immunogenic and therapeutic importance.

PMID- 9934692
TI  - Alternative mechanisms of interaction between homotypic and heterotypic
      parainfluenza virus HN and F proteins.
AB  - Cell fusion by human parainfluenza virus (HPIV) type 2 or type 3 requires the
      coexpression of both the fusion (F) and haemagglutinin-neuraminidase (HN)
      glycoproteins from the same virus type, indicating that promotion of fusion
      requires a type-specific interaction between F and HN. In this report we have
      further investigated the interaction of the ectodomains of the F and HN
      glycoproteins from HPIV2 and HPIV3. We constructed mutants of the HPIV2 F and
      HPIV3 F proteins (F'-KDEL) lacking a transmembrane anchor and a cytoplasmic tail,
      and containing a C-terminal signal for retention in the endoplasmic reticulum
      (ER). The P12 and P13 F'-KDEL proteins were both found to be retained
      intracellularly, and neither could induce cell fusion when co-expressed with
      homotypic HN proteins. Qualitative and quantitative cell-fusion assays also
      showed that both the P12 F'-KDEL and P13 F'-KDEL proteins have inhibitory effects
      on P12 F- and HN-induced cell fusion. However, the F-KDEL mutants were found to
      inhibit cell fusion by two distinct mechanisms. An interaction between P12 F'
      KDEL and P12 HN results in intracellular retention of HN, and a block in its
      transport to the cell surface. In contrast, P13 F'-KDEL was found to suppress the
      steady-state intracellular expression levels of HPIV2 HN. These results support
      the conclusion that fusion involves an interaction between the HN and F proteins,
      and suggest that an association between F and HN may occur in the ER.

PMID- 9934693
TI  - RNA editing-like phenomenon in paramyxovirus V gene mRNA observed in insect cells
      infected with a recombinant baculovirus.
AB  - The V gene of the paramyxovirus human parainfluenza virus type 2 (hPIV2) is
      transcribed into both V and P mRNA. The V mRNA is a faithful transcript of the V
      gene; however, the P mRNA is transcribed by an RNA-editing mechanism in hPIV2
      infected mammalian cells. Recombinant baculoviruses (rBV) were constructed
      containing the wild-type V gene, which has seven G residues at its editing site,
      and a manipulated V gene with ten G residues at its editing site. A small amount
      of the P protein was synthesized, in addition to the V protein, when the wild
      type V gene was expressed in rBV-infected insect cells. Furthermore, synthesis of
      the P protein increased when rBV containing the manipulated V gene was used to
      infect insect cells. Both the P and V proteins were detected after in vitro
      translation of mRNA from rBV-infected cells. Moreover, G-residue insertions and a
      deletion were detected in mRNA. Since the P protein was not detected after in
      vitro translation of V RNA that had been transcribed in vitro by T7 RNA
      polymerase, these results suggest that the non-encoded G residues were inserted
      and deleted during transcription in insect cells. This RNA editing-like
      phenomenon and the implications of the length of the G cluster are discussed.

PMID- 9934694
TI  - Evolutionary pattern of the G glycoprotein of human respiratory syncytial viruses
      from antigenic group B: the use of alternative termination codons and lineage
      diversification.
AB  - Partial sequences of the G protein gene of 33 isolates from antigenic group B of
      human respiratory syncytial virus were determined. Phylogenetic analysis
      indicated that the evolutionary pattern of group B viruses is similar to that
      previously described for isolates of antigenic group A, including worldwide
      distribution of related viruses and co-circulation of viruses from different
      lineages during the same epidemic. Dominance of AG+GA over UC+CU transitions was
      observed when G sequences of group B viruses were compared, as previously found
      in viruses from antigenic group A. Interestingly, differences in protein length,
      determined by the usage of alternative termination codons, were more pronounced
      in group B than in group A viruses. Changes in protein length correlated with the
      classification of viruses in different lineages. Thus, mutations that determined
      termination codon usage seem to have played an important role in the
      diversification of group B viruses.

PMID- 9934695
TI  - Complete nucleotide sequence of Newcastle disease virus: evidence for the
      existence of a new genus within the subfamily Paramyxovirinae.
AB  - We have completely sequenced the genome of Newcastle disease virus (NDV) vaccine
      strain LaSota. The sequences of the 3'- and 5'-terminal ends of the RNA genome
      were determined by sequencing cDNA fragments generated by rapid amplification of
      cDNA ends. The entire genomic sequence, which was established by sequencing cDNA
      fragments generated by high-fidelity RT-PCR, consists of 15186 nt. Comparison of
      the 5'-terminal sequence of NDV LaSota with the 5'-terminal sequences of ten
      members of the Paramyxovirinae showed that NDV LaSota has an unusually long 5'
      untranscribed region. Comparison of the entire genomic sequences showed that NDV
      is only distantly related to the other members of the genus Rubulavirus, to which
      NDV has been assigned. In this paper we present data which suggest that NDV
      should not be classified in the genus Rubulavirus, but instead should be
      considered as a member of a new genus within the subfamily Paramyxovirinae.

PMID- 9934696
TI  - Role of neuraminidase in influenza virus-induced apoptosis.
AB  - The virulent influenza virus clone 7a produced a greater level of apoptosis in
      MDCK cells compared with the attenuated strain A/Fiji. In both cases, apoptosis
      could be partially blocked by treatment with three anti-neuraminidase compounds
      [4-amino-(GR121158A) and 4-guanidino- (GG167; Zanamivir) 2,3-dehydro-N
      acetylneuraminic acid and 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA)]
      when they were given to cells during the virus attachment/entry phase, but not
      subsequent to this phase. In contrast, GG167, which does not enter cells, did not
      affect the numbers of infected cells and, in addition, acted late in the
      infection cycle to inhibit virus yields. Clone 7a neuraminidase was more active
      than A/Fiji neuraminidase when fetuin was used as the substrate. Similar
      differences in activity between the two viruses were seen when alpha-2,6 sialyl
      lactose was used as a substrate, but not with alpha-2,3 sialyl lactose. No
      sequence differences in the enzyme active site of the two neuraminidases were
      observed, indicating that differences in neuraminidase specificity and activity
      may be dictated by other residues. These results suggest that neuraminidase plays
      some role in the induction of apoptosis and that it acts prior to or during virus
      entry. However, apoptosis was considerably reduced when UV-irradiated virus,
      which retains >75% of its neuraminidase activity, was used. In addition, ammonium
      chloride, used to prevent virus entry, reduced virus-induced apoptosis.
      Amantadine, which inhibits virus uncoating, also inhibited apoptosis induced by
      the amantadine-sensitive strain A/Udorn/307/72 (H3N2), but not the amantadine
      resistant clone 7a. Hence, one or more intracellular processes are also involved
      in influenza virus-induced apoptosis.

PMID- 9934697
TI  - Involvement of the cytoskeleton in Junin virus multiplication.
AB  - The role of the cellular cytoskeleton in Junin virus (JV) infection was explored
      in two ways. Firstly, the action of inhibitors that affect individual
      cytoskeletal systems (microtubules or microfilaments) selectively was analysed.
      It was found that perturbations of microtubule or microfilament networks caused
      by colchicine, nocodazole, nifedipine, EGTA or DMSO strongly affected virion
      production and viral protein expression at non-cytotoxic concentrations.
      Secondly, the extent of association of viral proteins and infectious virus
      particles with the cytoskeletal fraction of monkey Vero cells was determined by
      using three non-ionic detergents, Triton X-100 (TX-100), NP-40 and octyl
      glucoside (OG). The cytoskeleton retained nearly 70% of the external JV envelope
      glycoprotein GP38 and about 40% of the JV nucleoprotein NP, according to TX-100
      and OG insolubility results. Furthermore, 1% of the total cell-bound infectivity
      was detected in the detergent-insoluble fraction, suggesting that cytoskeletal
      components are involved in the initiation of the assembly and budding processes
      of JV particles at the plasma membrane.

PMID- 9934698
TI  - Isolation and biological characterization of 3(2H)-isoflavene-resistant and 
      dependent poliovirus type 2 Sabin mutants.
AB  - Poliovirus type 2 Sabin mutants were selected for drug resistance and dependence
      by plating on HeLa cell monolayers in the presence of 3(2H)-isoflavene, a
      compound related to dichloroflavan, which prevents the shut-off of host
      translation and poliovirus RNA and protein synthesis. The drug-resistant mutants
      grew equally well in the presence and in the absence of the drug, while the drug
      dependent mutants only grew in the presence of the compound. One dependent and
      one resistant mutant were characterized biologically in more detail. The
      resistant mutant did not exhibit thermolability. The mild thermolability
      exhibited by the dependent mutant was not affected by the addition of 3(2H)
      isoflavene, indicating that the substance does not bind the poliovirus type 2
      Sabin capsid. The translation of viral proteins and the shut-off of host protein
      translation during cell infection were not inhibited in either mutant. In the
      absence of the drug, the cleavage of the precursor VPO, a step in virus protein
      processing, was affected in the dependent mutant. The dependence of the mutant on
      the drug was due to the inability of 75S empty particles to reach maturation: our
      results strongly suggest that this phenomenon is strictly dependent on the
      reduction of RNA synthesis, confirming the existence of a dynamic equilibrium
      between RNA production and genome encapsidation during the poliovirus replication
      cycle.

PMID- 9934699
TI  - A divergent genotype of hepatitis E virus in Chinese patients with acute
      hepatitis.
AB  - Recent studies have reported and provided nucleotide sequence data from divergent
      isolates of hepatitis E virus (HEV), including isolates from North America and
      Africa. Sera were investigated from 29 Chinese patients with a diagnosis of acute
      hepatitis and who were negative for hepatitis viruses A-E by serology (HEV was
      excluded by testing for IgG antibody only). To determine whether some patients
      were infected with HEV but had yet to seroconvert to antibody positivity, RT-PCR
      was carried out with primers designed within conserved sequences of the HEV open
      reading frame (ORF) 1 and ORF2 regions. Fifteen patients were found to harbour
      sequences related to HEV. Analysis of the HEV products revealed that nucleotide
      sequences from nine of the sera closely matched Burmese-like HEV sequences (more
      than 92% nucleotide identity across ORF1 and 88% in ORF2). The remaining six HEV
      isolates were similar to each other but divergent from all other known HEV
      sequences (74 to 83% nucleotide identity in ORF1 or ORF2). Phylogenetic analysis
      suggests that the six divergent isolates represent a fourth genotype of HEV,
      distinct from the previously described Burmese, Mexican and United States
      variants (genotypes 1, 2 and 3). This novel variant, referred to here as the
      Chinese genotype (genotype 4), may be responsible for a significant proportion of
      cases of acute hepatitis in China, as seen by the fact that 40% of the HEV
      infected patients in this study were genotype 4 positive.

PMID- 9934700
TI  - Sequence analysis and genetic classification of tick-borne encephalitis viruses
      from Europe and Asia.
AB  - The epidemiology of tick-borne encephalitis virus was investigated by comparative
      sequence analysis of virus strains isolated in endemic areas of Europe and Asia.
      Phylogenetic relationships were determined from the nucleotide and amino acid
      sequences of the major envelope (E) protein of 16 newly sequenced strains and
      nine previously published sequences. Three genetic lineages could be clearly
      distinguished, corresponding to a European, a Far Eastern and a Siberian subtype.
      Amino acids characteristic for each of the subtypes ('signature' amino a cids)
      were identified and their location in the atomic structure of protein E was
      determined. The degree of variation between strains within subtypes was low and
      exhibited a maximum of only 2.2% at the amino acid level. A maximum difference of
      5.6% was found between the three subtypes, which is in the range of variation
      reported for other flaviviruses.

PMID- 9934701
TI  - Helper T cell determinant peptide contributes to induction of cellular immune
      responses by peptide vaccines against hepatitis C virus.
AB  - The capacity of novel subunit vaccines to generate cytotoxic T lymphocytes (CTLs)
      against hepatitis C virus (HCV) was assessed. BALB/c mice were immunized with
      peptides based on the CTL and helper T cell (Th) epitopes of the HCV core, with a
      mixture of CTL and Th peptides (CTL+Th) or with a conjugated Th-CTL peptide. Mice
      immunized with CTL, CTL+Th and Th-CTL peptides, but not those immunized with Th
      peptide, developed HCV core CTL epitope-specific effector cells. Cytotoxic
      activity induced by immunization with Th-CTL was much higher than that induced by
      immunization with CTL+Th or CTL alone. However, rapid and high cytotoxic
      activities against HCV core were not only detected after immunization with
      peptides containing the CTL epitope but also as a result of infection with
      recombinant vaccinia virus carrying the HCV core gene after immunization with the
      Th epitope alone. Immunization with peptides containing the Th epitope also
      elicited spleen cell proliferation. This study demonstrates the capacity of both
      Th and CTL activated peptide vaccines to elicit CD8+, MHC class I-restricted
      CTLs. The capacity of such CTLs to contribute towards a protective and/or
      pathogenic immune response against HCV can now be assessed in mouse models.

PMID- 9934702
TI  - Molecular characterization and expression of the S3 gene of muscovy duck reovirus
      strain 89026.
AB  - Although reovirus infection is one of the major virus diseases of muscovy ducks
      in France, no vaccine is available and nothing is known about the structure and
      function of the genes and proteins of the reovirus involved. The complete S3
      genome segment of the muscovy duck reovirus strain 89026 has been cloned and the
      nucleotide and deduced amino acid sequences are reported here. The S3 genome
      segment is 1201 bp long and possesses the same terminal motifs (5' GCTTTTT and
      TATTCATC 3') as the S3 genome segment of known chicken reovirus strains. It
      contains one open reading frame that encodes a protein of 367 amino acids with a
      molecular mass of 40.8 kDa. The gene, encoding the sigmaB major outer-capsid
      protein, was cloned into two different baculovirus transfer vectors and expressed
      in insect cells as a glutathione S-transferase fusion protein or a non-fused
      protein. The antigenicity of the two recombinant proteins was demonstrated by
      immunoblot assay. The potential immunogenic role of sigmaB protein was studied in
      a protection assay against reovirus infection of specific-pathogen-free muscovy
      ducks. No antibodies could be detected by ELISA or immunoblot in ducks immunized
      with the recombinant proteins and no significant protection was noted after the
      challenge. However, whereas the weights of wild-type baculovirus-infected and
      challenge-control ducks were significantly lower than those of unchallenged
      ducks, the weights of male ducks previously immunized with the sigmaB recombinant
      proteins did not differ significantly from males of either group. This work is
      the first to provide molecular data for a duck reovirus.

PMID- 9934703
TI  - Molecular characterization of double-stranded RNA segments encoding the major
      capsid proteins of a Palyam serogroup orbivirus that caused an epizootic of
      congenital abnormalities in cattle.
AB  - cDNA cloning of the double-stranded RNA genome of Chuzan virus, a member of the
      Palyam serogroup orbiviruses, was carried out and the complete nucleotide
      sequences of RNA segments 2, 3, 6 and 7, encoding the major capsid proteins VP2,
      VP3, VP5 and VP7, respectively, were determined. The individual segments had
      single open reading frames and short inverted repeats adjacent to the conserved
      terminal sequences. Comparative sequence analysis with other serogroups of the
      genus Orbivirus suggested that VP2 is the principal determinant of serotype
      specificity and the neutralizing antigen of the Palyam serogroup. VP5 is also
      considered to be associated with antigenic variability. Both VP3 and VP7 probably
      contain serogroup-specific epitopes. Phylogenetic profiles demonstrated that the
      Palyam serogroup virus is more closely related to African horsesickness virus
      than to bluetongue virus and epizootic haemorrhagic disease virus.

PMID- 9934704
TI  - Role of class I major histocompatibility complex-restricted and -unrestricted
      suppression of human immunodeficiency virus type 1 replication by CD8+ T
      lymphocytes.
AB  - CD8+ T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1)
      carriers (ACs) are capable of suppressing HIV-1 replication in CD4+ peripheral
      blood mononuclear cells (PBMC) by a variety of known and unknown mechanisms. In
      the present study, cell contact-dependent, major histocompatibility complex type
      I (MHC I)-unrestricted, CD8+ cell-mediated suppression of HIV-1 LAI replication
      was detected. CD8+ PBMC of ACs suppressed HIV-1 replication more efficiently in
      MHC I-matched CD4+ PBMC than in mismatched cells. However, even when MHC I was
      totally mismatched, CD8+ cells still suppressed replication to a considerable
      extent in CD4+ PBMC. This MHC I-unrestricted, CD8+ cell-mediated HIV-1
      suppression required cell contact and was not effective against cells of the
      established T cell line ILT-KK. In contrast, MHC I-restricted HIV-1 suppression
      by CD8+ T cells was detected when ILT-KK cells were used as a target. By using
      these systems, we examined MHC I-restricted and -unrestricted suppressive
      activities of CD8+ cells in various donors in more detail. Although both types of
      CD8+ cell-mediated HIV-1 suppression diminished at the advanced stage of the
      infection, MHC I-unrestricted suppression diminished earlier than MHC I
      restricted suppression, in parallel with the decline in CD4+ T cells. These
      results suggest that suppression by the MHC I-restricted mechanism alone may fail
      to protect against CD4+ T-cell loss at the late stage of infection.

PMID- 9934705
TI  - A human immunodeficiency virus type 1 Env-granulocyte-macrophage colony
      stimulating factor fusion protein enhances the cellular immune response to Env in
      a vaccinia virus-based vaccine.
AB  - Vaccinia virus (VV) infection induces protective T- and B-cell responses, making
      recombinants based on VV good candidates for the development of effective
      vaccines to other viruses. VV recombinants expressing the human immunodeficiency
      virus (HIV) envelope protein (Env) have been generated in several laboratories
      and shown to induce anti-HIV cellular and humoral immune responses in vaccinated
      humans and in chimpanzees. To increase the immunogenicity of the Env antigen, a
      VV recombinant was generated that expresses a chimeric antigen consisting of the
      Env protein fused to an immunostimulatory cytokine, granulocyte-macrophage colony
      stimulating factor (GM-CSF). The chimeric protein retained GM-CSF biological
      activity when expressed by this recombinant virus (VV-GM-gp120) in cells infected
      in vitro. Infection of BALB/c mice with VV-GM-gp120 triggered a higher HIV
      specific cellular immune response, as measured by interferon-gamma production,
      than that induced by a VV recombinant expressing the native Env protein.
      Moreover, although anti-gp120 antibody titres were similar in sera from mice
      inoculated with either of the VV recombinants, immunization with the recombinant
      expressing the fusion protein elicited antibodies against a broader spectrum of
      Env epitopes. These results indicate that HIV Env antigen fusion to GM-CSF
      provides a means to improve the anti-HIV immune response.

PMID- 9934706
TI  - Properties and mechanism of action of a 17 amino acid, V3 loop-specific
      microantibody that binds to and neutralizes human immunodeficiency virus type 1
      virions.
AB  - Only two virus-neutralizing peptide microantibodies (MicroAbs) have been
      described and little is known about their mode of action. This report concerns a
      17 amino acid cyclized MicroAb, derived from the third complementarity
      determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same
      minimum epitope in the V3 loop of the gp120 envelope protein of human
      immunodeficiency virus type 1 (HIV-1) as the MAb. The MicroAb was able to bind to
      and neutralize free virus particles. It was up to 5-fold more efficient in mass
      terms than F58 IgG and its neutralization rate on a molar basis was only 32-fold
      lower. The mechanism of neutralization of the MicroAb was also investigated. A
      high level of neutralization (99%) occurred without any significant decrease in
      attachment of virus to target C8166 cells. Neutralized virus attached to CD4, the
      HIV-1 primary receptor. Fusion of virions to cells was partially inhibited by the
      MicroAb, whereas F58 IgG has been shown to inhibit fusion significantly. Thus,
      neutralization by the MicroAb appears to be mediated, at least in part, by
      inhibition of fusion. Control peptides, in which the tyrosine at position 5 or 6
      was deleted or changed to phenylalanine, showed no antiviral activity, attesting
      to the specificity of interaction of the MicroAb with the virion. It therefore
      appears that the MicroAb acts like an immunoglobulin. The data also show that the
      MicroAb/MAb F58 epitope on the V3 loop is not involved in attachment of virus to
      CD4 but is required for subsequent events in early infection.

PMID- 9934707
TI  - The antibody response of cattle infected with bovine immunodeficiency virus to
      peptides of the viral transmembrane protein.
AB  - The development of the antibody response to peptides of the transmembrane
      glycoprotein of bovine immunodeficiency virus (BIV) was followed over a period of
      50 weeks in six cattle experimentally infected with the BIV(FL112) isolate.
      Antibody was detected by an enzyme immunoassay using either a linear or a
      cyclized peptide with structural features common to an immunodominant region of
      other lentiviruses. The assay was specific for BIV, detecting antibody in bovine
      sera to BIV(FL112) or BIV(R29) but not to six other common viruses of cattle.
      Antibody was present in the sera of all cattle inoculated with BIV(FL112) within
      4 weeks of infection, peaked between 10 and 30 weeks and persisted in most cattle
      during the 50 weeks of observation. These features indicate that this assay may
      be useful in identifying cattle infected with other strains of BIV in the field.

PMID- 9934708
TI  - Comparative sequence analysis and predictions for the envelope glycoproteins of
      foamy viruses.
AB  - The foamy viruses (FVs) are a genus of complex retroviruses that has recently
      been found to possess several novel molecular features. There is increasing
      interest in the development of FVs as novel vectors for gene delivery. As there
      are remarkably few published studies of FV proteins, these recent findings
      prompted us to predict the structural features of FV glycoproteins with the aid
      of computer programs. We analysed all seven available FV Env sequences, a greater
      number of sequences than in previously published analyses. The relative rates of
      change for FV structural proteins were Pol < Env < Gag in increasing order, which
      differs from all other retroviruses. We determined that this difference is
      primarily caused by a higher relative rate of change for FV Gag proteins. We
      analysed the functional domains of FV glycoproteins and found that their
      structural organization was generally similar to other retroviruses. Putative
      structures were identified for the signal peptide, cleavage site, fusion peptide,
      membrane-spanning domain and the unique endoplasmic reticulum retrieval signal.
      Based on the predicted secondary structure of the transmembrane glycoprotein (TM)
      subunit, gp47, we also identified a unique prolonged central 'sheets and loops'
      region as the dominant feature of an unusually lengthy TM ectodomain. This
      lengthy central domain was flanked at each end by alpha-helices. The predictions
      reported here will stimulate and facilitate experimental approaches to better
      understand the structure and function of FV glycoproteins, and should assist in
      the planning and development of FV vectors.

PMID- 9934709
TI  - Diversity of human endogenous retrovirus class II-like sequences.
AB  - Class II human endogenous retroviruses (HERVs), often referred to as mouse
      mammary tumour virus (MMTV)-like or HERV-K elements, have similarities to several
      animal infectious retroviruses. Single clones from each of nine class II HERV
      groups (NMWV 1 to NMWV 9), isolated from a human breast cancer cell genomic
      library, were sequenced over a 244 bp stretch of the conserved reverse
      transcriptase region. These sequences were aligned to related exogenous and
      endogenous retroviruses and a phylogenetic tree was constructed. Sequences with
      more than 80% identity were considered as members of one group and we report here
      that the class II HERV family consists of at least ten groups. Three of the
      sequenced clones, from groups NMWV 3, 7 and 9, could not be related to any other
      previously identified elements and constituted their own groups. NMWV 8 had no
      similarity to any retroviral sequences in the sequenced region and is so far
      considered to be non-retroviral.

PMID- 9934710
TI  - Novel endogenous retroviral sequences in the chicken genome closely related to
      HPRS-103 (subgroup J) avian leukosis virus.
AB  - HPRS-103, the prototype of avian leukosis virus (ALV) subgroup J, is a recently
      identified retrovirus associated with myeloid leukosis in meat-type chickens.
      Although this virus shows high sequence identity to other ALV subgroups within
      the gag and pol genes, its env gene is highly diverged (with only about 40%
      sequence identity) from other ALV subgroups. On the other hand, the sequence of
      the env gene of HPRS-103 was 75% identical to that of E51, a member of the EAV
      family of endogenous avian retroviruses. It is reported here that the chicken
      genome also contains another EAV-related element, EAV-HP, showing much greater
      sequence identity (over 97%) to the HPRS-103 env gene. Southern blotting analysis
      showed that EAV-HP-related sequences were distinct from EAV-O and were present in
      all lines of chicken examined and in grey jungle fowl, but were absent from
      several other avian species. The potential role of these endogenous sequences in
      the evolution of ALV subgroup J viruses is discussed.

PMID- 9934711
TI  - The minor coat protein of beet yellows closterovirus encapsidates the 5' terminus
      of RNA in virions.
AB  - Filamentous particles of beet yellows closterovirus (BYV) are built of two
      related capsid proteins, of which the minor species, p24, forms a 75 nm tail at
      one end of the virion. In the present work, we used polyclonal antibodies against
      p24 for isolating the 'tailed' virion segments from sonicated BYV particle
      preparations. The [gamma-32P]ATP-labelled RNA obtained from the antibody-selected
      particle segments consistently showed stronger hybridization with the 5'-terminal
      BYV cDNA clones than with the 3'-terminal cDNA clones. These data clearly
      indicate that it is the 5'-terminal portion of the closterovirus RNA genome that
      is encapsidated by p24.

PMID- 9934712
TI  - Similarities in the genome organization of tobacco rattle virus and pea early
      browning virus isolates that are transmitted by the same vector nematode.
AB  - Although sequence data have been obtained for several tobravirus isolates, only
      two of these isolates are nematode-transmissible. Tobacco rattle virus (TRV)
      PpK20 is transmitted by Paratrichodorus pachydermus, whereas pea early-browning
      virus (PEBV) TpA56 is transmitted by Trichodorus primitivus. To clarify whether
      differences in the genome structure of these isolates are relevant to the
      specificity of interactions with particular vector nematodes, or merely reflect a
      taxonomic difference between TRV and PEBV, we have sequenced RNA2 of a new
      isolate of TRV (TpO1) that is transmitted by the same vector nematode as PEBV
      TpA56 but is not transmitted by the nematode vector of TRV PpK20. TRV TpO1 RNA2
      encodes, in 5' to 3' order, a coat protein (CP), a 9K protein, a 2b (29K) protein
      and a 2c (18K) protein. Amino acid sequence comparison shows that both the CP and
      2b proteins of TRV TpO1 resemble more closely the analogous proteins from PEBV
      TpA56 than those from TRV PpK20. Also, the TRV TpO1 9K protein has similarities
      with the PEBV 9K protein whereas this protein is lacking in TRV PpK20.

PMID- 9934714
TI  - Maternal health and pre- and perinatal characteristics in the etiology of
      testicular cancer: a prospective population- and register-based study on
      Norwegian males born between 1967 and 1995.
AB  - OBJECTIVES: The aim of the present prospective study was to identify possible
      risk factors of testicular cancer (TC) in relation to gestation and birth.
      METHODS: Based on data from compulsory birth and cancer registration in Norway,
      odds ratios (ORs) of TC were estimated. RESULTS: Among 868068 males born between
      1967 and 1995, 268 cases of germ cancer had developed by June 1996, 32 TCs before
      5 years of age and 236 TCs thereafter, 48 cases being seminomas and 220 non
      seminomas. There was a tendency of an inverse association between parity and TC.
      A previous finding from Sweden linking neonatal jaundice to risk of non-seminomas
      was confirmed (adjusted OR = 2.1, 95 percent confidence interval [CI] = 1.3-6.9).
      Significant associations were also seen for seminomas and TC diagnosed after 5
      years of age. Maternal disease diagnosed before pregnancy increased the risk of
      TC significantly, particularly in the age group 0-4 years: Adjusted OR = 3.0, CI
      = 1.4-6.3. Retained placenta was significantly associated with both seminomas and
      non-seminomas and with TC diagnosed after 5 years of age. CONCLUSIONS: The
      findings of this study support the existing hypothesis that pre- and perinatal
      risk factors are of significance for development of TC in children and in young
      adults, and for seminomas and non-seminomas. The hypothesis that estrogens are
      involved in TC development was, among other factors, supported by the association
      of parity to TC. Additionally, on the basis of findings in maternal diseases and
      complications to pregnancy, we suggest that immune reactions during foetal life
      may be of significance for development of TC.

PMID- 9934713
TI  - Dietary factors and the risk of squamous cell esophageal cancer among black and
      white men in the United States.
AB  - OBJECTIVES: To investigate dietary factors for squamous cell esophageal cancer
      and whether these factors may contribute to the five-fold higher incidence of
      this cancer in the black versus white population of the United States. METHODS:
      Data from a food frequency questionnaire were analyzed for 114 white men and 219
      black men with squamous cell esophageal cancer, and 681 white and 557 black male
      controls from three areas of the United States who participated in a population
      based case-control study of esophageal cancer. RESULTS: Protective effects were
      associated with intake of raw fruits and vegetables (odds ratio for high versus
      low consumers = 0.3 in both white and black men) and use of vitamin supplements
      (especially vitamin C; odds ratio for high versus low consumers = 0.4 in both
      races), with the frequency of consumption of raw fruits and vegetables and
      vitamin supplements being greater for white than black controls. In addition,
      elevated risks were associated with high versus low intake of red meat (OR = 2.7
      for blacks and 1.5 for whites) and processed meat (OR = 1.6 for blacks and 1.7
      for whites), with the levels of consumption being greater for black than white
      controls. CONCLUSIONS: In the United States, these dietary factors may contribute
      in part to the much higher incidence of squamous cell esophageal cancer among
      black compared to white men.

PMID- 9934715
TI  - Physical activity and cancer etiology: associations and mechanisms.
AB  - OBJECTIVES: This paper reviews the epidemiologic data of associations between
      physical activity and cancer risk, describes potential mechanisms for a physical
      activity cancer link, and proposes future directions for research. METHODS: We
      reviewed English-language published papers on physical activity and cancer
      through Medline searches for epidemiologic studies, and through references on
      individual reports. We reviewed general texts on effects of exercise on human
      biology and applied the concepts to the biology of cancer in humans to describe
      potential mechanisms for a physical activity-cancer association. RESULTS:
      Considerable epidemiologic evidence has accrued linking increased physical
      activity with reduced occurrence of cancers of the breast and colon. The
      association between physical activity and cancers of other sites is unclear.
      Potential mechanisms for the association between physical activity and reduced
      risk for breast and colon cancer are varied: they range from bias due to physical
      activity's strong correlations with other health factors (e.g., diet, smoking,
      alcohol use, use of medications) to the metabolic effects resulting from
      increased physical activity and fitness, such as reduced obesity, hormonal and
      reproductive effects, mechanical effects, and enhancement of the immune system.
      CONCLUSIONS: The elucidation of biologic mechanisms for an association between
      physical activity and cancer may provide biological support for the association.
      It will contribute information to determine the type, frequency, and duration of
      exercise needed to maximize protection. This information will be needed before
      large-scale community interventions are begun, in order to choose the correct
      interventions for the desired effect of reduced incidence of the most common
      cancers.

PMID- 9934716
TI  - Evaluating local differences in breast cancer incidence rates: a census-based
      methodology (United States).
AB  - OBJECTIVES: We used readily accessible, existing data to assess whether or not
      geographic variation in breast cancer incidence rates in the San Francisco Bay
      Area was related to the unequal distribution of known breast cancer risk factors.
      METHODS: Cancer registry and 1990 census block-group data were used to look at
      the associations between breast cancer incidence and known risk factors
      (including parity, urban/rural status, and socioeconomic indicators) in 25
      California counties. Average annual age-adjusted invasive breast cancer incidence
      rates were calculated for the period 1988-1992, and adjusted morbidity ratios
      were computed. RESULTS: While breast cancer incidence in Marin County was 9
      percent higher than that of the other 24 counties combined (relative risk = 1.09,
      95 percent confidence interval = 1.01-1.18), this increase appeared to be due to
      the unequal distribution of known risk factors. Block-groups that had a high
      level of any risk factor had higher incidence rates, regardless of geographic
      location. After multivariate adjustment, breast cancer incidence no longer
      differed between Marin and the other counties (adjusted morbidity ratio = 1.02).
      CONCLUSIONS: The results suggest that the unequal distribution of known risk
      factors was responsible for Marin County's high breast cancer incidence rate.

PMID- 9934717
TI  - The role of prostate-specific antigen (PSA) testing patterns in the recent
      prostate cancer incidence decline in the United States.
AB  - OBJECTIVES: Trends in first-time and later PSA procedure rates are ascertained
      using longitudinal data from a population-based cohort. These trends are compared
      to trends in prostate cancer incidence to determine the role of PSA in the recent
      decline in prostate cancer incidence. METHODS: Medicare data were linked with
      tumor registry data from the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) Program. A 5 percent random sample (n =
      39985) of Medicare beneficiaries from the SEER areas without a previous diagnosis
      of prostate cancer as of January 1, 1988 was followed through 1994. Trends in
      first-time PSA use were distinguished from those of second or later for men
      without diagnosed prostate cancer. RESULTS: Trends in the rate of first-time PSA
      procedures track closely with trends in prostate cancer incidence rates,
      increasing until 1992 and decreasing thereafter. Similar patterns were observed
      by race and age group. Geographic variability in the dissemination of PSA
      screening was observed, yet the association between testing and incidence
      remained. Men in the cohort had a 4.7 percent chance of being diagnosed within
      three months of an initial PSA test, with the percentage falling for subsequent
      tests. CONCLUSIONS: It is informative to distinguish first from later tests when
      assessing the effect of the diffusion of a test in a population. Taking this
      approach was useful in illuminating the role of PSA testing in a reversal of a
      long-term increase in prostate cancer incidence rates.

PMID- 9934718
TI  - An extended study on childhood malignancies in the vicinity of German nuclear
      power plants.
AB  - OBJECTIVES: The study was performed to validate exploratory results obtained in a
      former study on the incidence rates of childhood malignancies in the vicinity of
      German nuclear power plants and to evaluate the confirmatory results of this
      previous study. METHODS: Incidence rates near German nuclear installations were
      compared to rates in control regions based on the German Childhood Cancer
      Registry. RESULTS: No exploratory result could be reproduced. This is also true
      for children with acute leukemia younger than 5 years who were living within a 5
      km radius of an installation: an observed relative risk (RR) of 1.39 was not
      significantly increased (95 percent confidence interval CI: 0.69-2.57). Former
      confirmatory results could be confirmed again. A pooled analysis of both studies
      based on 2390 cases resulted in RR of 0.99 for all malignancies (CI: 0.91-1.07)
      and of 1.00 for acute leukemias (CI: 0.87-1.16) (children younger than 15 years
      of age living within a 15 km radius). CONCLUSIONS: Results did not show
      significantly increased incidence rates for any subgroup with previously
      significant exploratory results. Therefore, it appears to be most likely that the
      previous results were just due to chance. Evaluating the previously confirmatory
      results with the combined data from the two study periods reassures that
      incidence rates are not increased in children younger than 15 years who are
      living within a 15 km radius, either for all malignancies or for acute leukemias.
      We conclude that at present, in Germany no further investigations of this kind
      are necessary.

PMID- 9934719
TI  - Cholecystectomy and colon cancer.

PMID- 9934720
TI  - Asymptomatic primary biliary cirrhosis--should everyone be treated?

PMID- 9934721
TI  - Is manometry useful in dyspepsia?

PMID- 9934722
TI  - Unexplained chest pain at the turn of the century.

PMID- 9934723
TI  - Long term outcome of endoscopic drainage of pancreatic pseudocysts.

PMID- 9934724
TI  - Can the age limit for endoscopy be increased in dyspepsia patients who do not
      have alarm symptoms?

PMID- 9934725
TI  - Does antireflux surgery alter the natural history of Barrett's esophagus?

PMID- 9934726
TI  - Citizen soldiers: in the managed care trenches.

PMID- 9934727
TI  - Esophageal cancer. American College of Gastroenterology.

PMID- 9934728
TI  - Barrett's esophagus: the long and the short of it.
AB  - Specialized intestinal epithelium occurs more frequently at the gastroesophageal
      junction than previously anticipated. It can occur either within tongues of
      mucosa (short segment Barrett's) or just beneath a normal z-line (intestinal
      metaplasia at the gastroesophageal junction). Whether the etiopathogenesis and
      the natural history of these two conditions are the same is as yet unclear. The
      role of gastroesophageal reflux disease (GERD), Helicobacter pylori, and
      inflammation at the gastroesophageal junction in the pathogenesis of short
      segment Barrett's and intestinal metaplasia at the gastroesophageal junction
      needs to be carefully documented. Intestinal metaplasia at the gastroesophageal
      junction, short segment Barrett's, and Barrett's may represent a continuum of the
      same disease process. Recent evidence suggests, however, that short segment
      Barrett's shares similar characteristics with Barrett's but may be distinct from
      intestinal metaplasia at the gastroesophageal junction. It is conceivable that
      short segment Barrett's may remain steady or even regress if and when the noxious
      influence wanes but, with continuing stimulation, short segment Barrett's may
      lengthen further to become what we observe to be Barrett's. If correct,
      endogenous or exogenous factors that induce progression need to be identified.
      Acid and bile reflux and H. pylori are possible candidates acting either singly
      or synergistically. Finally, the true neoplastic potential of short segment
      Barrett's needs clarification.

PMID- 9934729
TI  - Cholecystectomy and the risk of colon cancer.
AB  - OBJECTIVE: The relationship between cholecystectomy and the occurrence of
      subsequent colon cancer has been controversial. Using data collected as part of
      an incident case-control study of colon cancer conducted in northern California,
      Minnesota, and Utah, we evaluated this association. METHODS: Participants were
      between 30 and 79 yr of age and had a first primary colon cancer diagnosed
      between October 1, 1991 and September 30, 1994. Analyses were adjusted for age,
      gender, family history of colorectal cancer, body mass index, dietary energy and
      fiber intake, use of aspirin or nonsteroidal antiinflammatory drugs, and long
      term leisure-time vigorous physical activity. RESULTS: A weak positive
      association between cholecystectomy and proximal colon cancer (odds ratio [OR]
      and 95% confidence interval [CI] 1.3 [1.0-1.6]) was observed. This was
      counterbalanced by a weak, nonsignificant negative association (OR 0.8, 95% CI
      0.6-1.1) with distal colon cancer leading to no overall association (OR 1.0, 95%
      CI 0.9-1.2). The association between colon cancer and cholecystectomy did not
      differ by gender or race, but it did differ by study area, with most of the
      increased association being attributed to the Minnesota population. The elevated
      risk of proximal colon cancer increased after cholecystectomy but disappeared
      after 14 years. CONCLUSIONS: Our results suggest that cholecystectomy or the
      underlying gallstone disease that prompts it may be related weakly to the risk of
      subsequent proximal colon cancer. However, the association may differ by
      geographic area of the country, and may be artifactual at least in part.

PMID- 9934730
TI  - Asymptomatic primary biliary cirrhosis: a study of its natural history and
      prognosis.
AB  - OBJECTIVE: To document the natural history of asymptomatic primary biliary
      cirrhosis and identify prognostic features that would predict the development of
      symptomatic disease. METHODS: A retrospective chart review of all patients with
      abnormal liver biochemical tests and antimitochondrial antibody-positive, liver
      biopsy-compatible primary biliary cirrhosis who were seen in a single tertiary
      care center between 1983 and 1994 was performed. Statistical analysis using Cox
      regression was employed to compare survival of the study population with an age-
      and gender-matched control population and to identify potential prognostic
      variables. RESULTS: Ninety-one patients were included. Median age at presentation
      was 53.2 yr. Ninety percent were female. Median follow up was 61.2 months (range
      7-206 months). Thirty-six percent (33 patients) became symptomatic with 11% (10
      patients) progressing to death or liver transplant. Median predicted length of
      survival from onset of disease for the entire cohort was 14 yr. Patient survival
      was less than that predicted for an age- and gender-matched control population (p
      < 0.05). Univariate and multivariate analysis on a broad spectrum of clinical,
      biochemical, and histological features at the time of initial presentation failed
      to reveal any prognostic variables that would distinguish those who would become
      symptomatic from those who would remain symptom-free. Specifically, three primary
      variables of interest (associated autoimmune disorders, hepatomegaly, and
      histological stage) were not found to predict prognosis. CONCLUSION: Patients who
      present with asymptomatic primary biliary cirrhosis have a shorter life span than
      the general population. Presently, there are no prognostic features that identify
      the patients who will develop progressive disease from those who will remain
      symptom-free. Therefore, treatment should be offered to all patients.

PMID- 9934731
TI  - Contractile patterns in patients with severe chronic dyspepsia.
AB  - OBJECTIVE: Antroduodenojejunal interdigestive and postprandial pressure
      recordings were analyzed in 41 consecutive patients referred for evaluation of
      severe chronic dyspepsia. In addition to traditional manometric evaluation we
      also focused on the propagation pattern of individual pressure waves in the
      proximal duodenum. METHODS: Catheters with closely spaced side holes for
      temporospatial analysis of the computerized recordings were used. The dominating
      symptoms were unexplained nausea and vomiting (n = 18), chronic abdominal pain (n
      = 16), or both (n = 7). The patients' mean age was 45 yr (31 women and 10 men).
      Gastric surgery had been performed on 11 patients. Results from 20 healthy
      volunteers served as a reference range. RESULTS: Findings were suggestive of
      neuropathy in 16 (39%) and myopathy in 1 (2.4%) using conventional criteria.
      Another 19 patients of the 24 with normal condensed recordings showed
      abnormalities in the propagation pattern of individual pressure waves in phase II
      and/or during the fed state, when compared with the controls. Absence of phase
      III of the migrating motor complex was found in 12 patients during the 5-h
      fasting recording, compared with none in the controls (p < 0.01).
      Retroperistalsis at the end of phase III in the duodenum was present in at least
      one of the activity fronts in all patients having migrating motor complex except
      one, which was similar to the controls. During phase II, unpropagated bursts of
      phasic and tonic activity were more frequent in patients than in controls (mean
      13.2% vs 3.7% of the time; p < 0.05), and a higher proportion of individual
      contractions was retrograde in patients than in controls (17.4% vs 5% of
      propagated contractions; p < 0.05). Patients had higher postprandial motility
      index in the distal duodenum than did controls (p < 0.05). Moreover, after
      feeding more individual contractions were retrograde in patients than in controls
      (33.1% vs 10% of propagated contractions; p < 0.01). Sequences of localized
      supratachyarrythmia, 25-35/min in the antrum and 50-60/min in the small bowel
      associated with symptoms, were observed in two patients. CONCLUSION: Manometry is
      important for demonstration of pathophysiology in patients with unexplained
      abdominal pain, nausea, and vomiting. Simultaneous analysis of the propagation of
      individual contractions of interdigestive and fed motility is superior to
      conventional manometry alone.

PMID- 9934732
TI  - Effects of octreotide on esophageal visceral perception and cerebral evoked
      potentials induced by balloon distension.
AB  - OBJECTIVE: Octreotide, a somatostatin analog, is antinociceptive and increases
      perception threshold in the rectum. The aim of this study was to determine
      whether octreotide alters esophageal sensory thresholds and cortical evoked
      potentials (CEPs) resulting from intraesophageal balloon distension. METHODS:
      Twelve healthy volunteers (six men and six women, median age 25 yr, range 21-60
      yr) underwent a randomized, double-blind, placebo-controlled trial of octreotide
      100 microg s.c. versus saline. A 30-mm balloon was inserted 5 cm above the lower
      esophageal sphincter without topical anesthesia. The balloon was inflated at a
      rate of 170 cc/s to a maximum of 30 cc in 2 cc steps. Both pressure and volume
      were recorded. Patients reported first sensation (S1) and maximally tolerated
      pain (S2). Two cycles were performed both preinjection and 40 min postinjection.
      Evoked potentials were recorded from Cz to linked ears over 50 balloon inflation
      cycles (volume = S2). RESULTS: Threshold volume to first sensation (S1) was
      significantly increased after octreotide injection [median (interquartile range):
      24 (14-26) cc vs 13 (9-21) cc, p < 0.02]. No significant alteration in volume
      causing pain (S2) was noted after octreotide injection [29 (25-30+) cc vs 22 (19
      29) cc]. Neither were volumes causing either first sensation [18 (11-24) cc vs 13
      (9-18) cc] or pain [27 (23-30) cc vs 23 (21-25) cc] significantly altered by
      placebo injection. Neither amplitude nor latency of any of the three peaks of the
      evoked potential recordings differed significantly between postplacebo and
      postoctreotide recordings. CONCLUSION: Octreotide significantly increased
      esophageal perception thresholds to balloon distension. It did not alter pain
      thresholds, nor were cortical evoked potentials to painful stimulation altered in
      normal subjects.

PMID- 9934733
TI  - Long term outcome of endoscopic drainage of pancreatic pseudocysts.
AB  - OBJECTIVE: Nonoperative drainage either by the percutaneous or endoscopic route
      has become a viable alternative to surgical drainage of pancreatic pseudocysts.
      Endoscopic drainage has been reported in a few small series with encouraging
      short term results. The aim of this study was to determine the indications,
      suitability, and long term outcome of transmural endoscopic drainage procedures.
      METHODS: All patients presenting over a 2-yr period to a tertiary referral
      hepatobiliary unit with pancreatic pseudocysts were studied. Endoscopic drainage
      was performed in patients with pseudocysts bulging into the stomach or duodenal
      lumen. Outcome measures were successful drainage of the pseudocyst,
      complications, and recurrence rates. RESULTS: Of 66 patients presenting with
      pseudocysts, 34 were considered suitable for endoscopic drainage. Twenty-four
      (71%) were successfully drained. Failures were associated with thick walled
      pseudocysts (> 1 cm), location in the tail of the pancreas, and pseudocysts
      associated with acute necrotizing pancreatitis. There were three recurrences
      (7%), two of which were successfully redrained endoscopically. The long term
      success rate (median follow-up, 46 months) of the initial procedure was 62%.
      CONCLUSION: Transmural endoscopic drainage is a safe procedure with minimal
      complications. It should be the procedure of choice for pseudocysts associated
      with chronic pancreatitis or trauma, with a wall thickness of < 1 cm and a
      visible bulge into the gastrointestinal lumen. Forty percent of pseudocysts
      fulfilled these criteria in our study.

PMID- 9934734
TI  - Does concern about missing malignancy justify endoscopy in uncomplicated
      dyspepsia in patients aged less than 55?
AB  - OBJECTIVE: There is increasing interest in using noninvasive H. pylori testing
      rather than endoscopy in determining the management of younger patients
      presenting with dyspepsia. However, there is concern that this approach may
      result in missing potentially curable malignancy. The aim of the study was
      therefore to assess whether concern over occult malignancy is valid in patients
      aged <55 yr presenting with uncomplicated dyspepsia. METHODS: A predetermined
      questionnaire was used to review the case notes of patients aged <55 yr who had
      presented with esophageal or gastric cancer between 1989 and 1993 within the
      Greater Glasgow Health Board population of 940,000. RESULTS: A total of 169
      patients aged <55 yr were diagnosed to have gastroesophageal malignancy over the
      5-yr period, representing an incidence of about 1 per 28,000 total population/yr.
      There were only five patients who were found to have upper GI malignancy when
      undergoing upper GI investigation in the absence of sinister symptoms. This
      represents an incidence of underlying malignancy in patients of <55 yr with
      uncomplicated dyspepsia of 1.06 per million total population/yr. Of these five
      patients, all had lymph node metastases at diagnosis and four had died between 2
      months and 3 yr of follow-up. CONCLUSIONS: Upper GI malignancy is extremely rare
      in patients <55 yr presenting with uncomplicated dyspepsia and, when found, is
      usually incurable. Consequently, concern about missing underlying curable
      malignancy is not a valid indication for endoscoping patients <55 yr presenting
      with uncomplicated dyspepsia.

PMID- 9934735
TI  - Histological and anatomic changes in Barrett's esophagus after antireflux
      surgery.
AB  - OBJECTIVE: The best treatment approach for patients with documented Barrett's
      esophagus remains controversial. There is currently no well designed prospective
      study examining the effect of successful antireflux surgery on Barrett's
      esophagus. METHODS: Fourteen patients with histologically proven Barrett's
      esophagus underwent standard antireflux surgery followed by careful endoscopic,
      histological, and symptomatic follow-up beginning at 2-4 wk after surgery. Pre-
      and postoperative symptoms, patient functional assessment scores, lower
      esophageal sphincter pressure, and 24-h pH studies were compared, in addition to
      monitoring patients for evidence of squamous re-epithelialization and dysplasia.
      RESULTS: Patients demonstrated statistically significant improvement in symptoms,
      functional assessment scores, lower esophageal sphincter pressure, and 24-h pH
      assessments after antireflux surgery. Two patients had complete disappearance of
      short segments (2 and 3 cm) of Barrett's esophagus. Ten additional patients
      demonstrated evidence of squamous re-epithelialization, although biopsies often
      showed mixed components of squamous and columnar epithelium. No patients showed
      progression of dysplastic change, and four patients demonstrated the
      disappearance of low grade dysplasia throughout the period of the study.
      CONCLUSION: Successful antireflux surgery can produce at least partial squamous
      re-epithelialization in Barrett's metaplasia and stabilization or apparent
      improvement in dysplasia in some patients without the need for long term
      medication. Continued long term endoscopic and histologic follow-up is still
      required in all patients with Barrett's esophagus after antireflux surgery.

PMID- 9934736
TI  - Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based
      study.
AB  - OBJECTIVE: We described incidence rates of esophageal adenocarcinoma in Denmark
      in a 20-yr period and determined the proportion of patients diagnosed with
      esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus,
      making them potential candidates for endoscopic surveillance. METHODS: Rates of
      esophageal and gastric cancers were collected from the Danish Cancer registry for
      the period 1970-1991. The registry was used to identify all cases of esophageal
      adenocarcinoma in the period 1987-1992. Medical records were retrieved and
      details concerning previous diagnosis of reflux disease and Barrett's esophagus
      were recorded. RESULTS: The age- and gender-adjusted incidence of esophageal
      adenocarcinoma increased eightfold, from 0.3/10(5)/yr in 1970 to 2.3/10(5)/yr in
      1990. This increase could not be explained by changes in classification or
      diagnostic routines. Medical data were retrieved for 524 of the 578 cases of
      esophageal adenocarcinoma reported during the period 1987-1992. A history of
      reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524
      patients. A total of 119 patients (23%) had previously been investigated for
      dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of
      Barrett's esophagus was found in only 1.3% of the cancer patients. CONCLUSIONS:
      The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a
      20-yr period, and this increase is not explained by changes in classification or
      diagnostic routines. More than 98% of esophageal adenocarcinomas were found in
      patients who could not have entered endoscopic surveillance, as Barrett's
      esophagus had not been diagnosed before the cancer diagnosis. Endoscopic
      surveillance to detect dysplasia may be an option for the individual patient with
      Barrett's esophagus, but these screening programs are not likely to reduce the
      death rate from esophageal adenocarcinomas in the general population.

PMID- 9934737
TI  - High- versus standard-dose ranitidine for control of heartburn in poorly
      responsive acid reflux disease: a prospective, controlled trial.
AB  - OBJECTIVE: H2-receptor antagonists are commonly used as initial therapy in
      patients with gastroesophageal reflux disease (GERD) and are frequently continued
      at the same or higher doses when symptoms persist after 4-6 wk of therapy. Our
      objective was to compare the efficacy of twice-daily treatment with either
      ranitidine 150 mg b.i.d. or 300 mg b.i.d. in resolving heartburn in GERD patients
      who remained symptomatic after 6 wk of therapy with ranitidine 150 mg b.i.d.
      METHODS: This was a two-phase, prospective study. In the first phase, GERD
      patients with heartburn on > or = 4 of the 7 days before entry were treated with
      open-label ranitidine 150 mg b.i.d. for 6 wk. In the second phase, patients who
      were still symptomatic were randomized to 8 wk of double-blind ranitidine therapy
      at either the same (150 mg b.i.d.) or a higher dose (300 mg b.i.d.). The primary
      efficacy variable was the resolution of heartburn at wk 4 and 8, as monitored
      through diary cards. RESULTS: Of the 481 patients treated for 6 wk in phase I,
      285 (59%) were still symptomatic; 271 patients (95% of those still symptomatic)
      were randomized to double-blind treatment with ranitidine. In phase II, 45% of
      the patients in each treatment group experienced no more than mild heartburn;
      complete heartburn resolution was observed in <20% of patients in either group at
      wk 4 and 8. There were no significant differences in efficacy between the two
      treatment groups. CONCLUSIONS: These results indicate that the majority of GERD
      patients still have symptoms of heartburn after 6 wk of ranitidine therapy. Only
      a minority of these patients experience complete relief of heartburn after an
      additional 8 wk of treatment, which demonstrates that doubling the dose of
      ranitidine is not efficacious.

PMID- 9934738
TI  - Comparative study of intestinal metaplasia and mucin staining at the cardia and
      esophagogastric junction in 225 symptomatic patients presenting for diagnostic
      open-access gastroscopy.
AB  - OBJECTIVE: Adenocarcinoma around the esophagogastric junction (EGJ) is increasing
      in incidence, and is frequently associated with areas of macroscopic or
      microscopic intestinal metaplasia (IM). The aim of this study was to define the
      incidence and type of metaplastic changes in the cardia and at the EGJ in
      symptomatic patients in whom there was no endoscopic columnar segment. METHODS:
      Patients attending for open-access gastroscopy had three sets of endoscopic
      biopsies taken at 3-cm intervals, from cardia, EGJ, and distal esophagus.
      Hematoxylin and eosin, Alcian blue/PAS (AB/PAS), and high-iron diamine/Alcian
      blue (AB/HID) were used to define and characterize IM. RESULTS: Of 225 patients,
      eight (4%) had carcinoma, eight (4%) had conventional long-segment Barrett's
      esophagus, 15 (7%) showed endoscopic short-segment Barrett's change, with no
      endoscopic Barrett's in 194 (86.2%). Of the latter, 34 (17.5%) had IM at the EGJ,
      and nine (4.6%) had IM at the cardia on hematoxylin and eosin. Acid mucin stains
      were positive at the EGJ in 135 (69.6%) and at the cardia in 75 (38.7%).
      Metaplasia at the EGJ was associated with sulphomucins (p < 0.0001) and involved
      the surface glandular epithelium (p < 0.0001) more frequently than the cardia.
      Metaplasia was not related to reflux symptoms, hiatus hernia, or endoscopic
      esophageal inflammation. Ninety percent of those with IM detectable by
      hematoxylin and eosin were taking acid suppression, compared with 72.8% overall.
      CONCLUSIONS: Intestinal metaplasia is very common at the esophagogastric junction
      and gastric cardia, with marked differences in incidence and characteristics of
      mucin staining between the two sites. The relationship of intestinal metaplasia
      to the development of carcinoma is yet to be determined.

PMID- 9934739
TI  - Factors correlated with number of metastatic lymph nodes in gastric cancer.
AB  - OBJECTIVE: We had previously reported a reasonable categorization of the number
      of positive lymph nodes (LN: 0, 1-4, 5-8, and > 8) as a prognostic indicator.
      This study was an extension, to see which factors correlated with number of
      positive lymph nodes. METHODS: A total of 533 patients with gastric
      adenocarcinoma, who underwent curative surgery between January 1988 and December
      1995, were entered into this study. Patients were divided into four groups
      according to metastatic LN number (0, 1-4, 5-8, and > 8). Their survival and
      clinicopathological factors were analyzed. RESULTS: A total of 16,457 LNs, with
      an average of 30.9 per specimen, were removed, of which 1686 (10.2%) showed
      metastases. The 5-yr cumulative survival rate decreased as the number of
      metastatic LNs increased, ie., 91.3% for LN 0; 67.4% for LN 1-4; 37.2 for LN 5-8,
      and 14.1% for LN > 8. Multivariate analyses showed that depth of cancer invasion
      (odds ratio: 2.4), gross appearance (odds ratio: 1.9), size (odds ratio: 1.9),
      and location (odds ratio: 1.4) of tumor were four independent factors correlated
      with the number of metastatic LNs. Number of metastatic LNs increased with
      advanced Japanese nodal stage and UICC-TNM stage. CONCLUSIONS: Depth of tumor
      invasion, and gross appearance, size, and location of tumor were four
      pathological factors independently correlated with number of metastatic LNs in
      gastric cancer.

PMID- 9934740
TI  - A prospective, multidisciplinary evaluation of premenopausal women with iron
      deficiency anemia.
AB  - OBJECTIVE: The cause of iron deficiency anemia (IDA) in premenopausal women is
      often presumed to be menstrual blood loss. The purpose of this study was to
      determine the diagnostic value of a comprehensive gynecological and
      gastrointestinal evaluation in premenopausal women with IDA. METHODS: Nineteen
      premenopausal, nonpregnant women older than 18 yr of age with IDA defined by a
      hemoglobin < 12 gm/dl with serum ferritin < 10 ng/ml participated in the study.
      Evaluations included directed history and physical examination by a specialist in
      gynecology and a subspecialist in gastroenterology, esophagogastroduodenoscopy,
      colonoscopy, upper gastrointestinal radiography with small bowel follow-through,
      antiendomysial antibody, and fecal occult blood tests. RESULTS: Seven of 19 (37%)
      premenopausal women with IDA were diagnosed to have a gynecological cause of
      anemia by a specialist in that field. Although only four of these seven patients
      had digestive complaints, all but one (86%) were discovered to have
      gastrointestinal disease by upper endoscopy; findings were duodenal ulcer and
      Helicobacter pylori (H. pylori) gastritis (one), esophagitis and H. pylori
      gastritis (one), erosive esophagitis (one), gastric arteriovenous malformations
      (one), and nodular/erosive H. pylori gastritis (two). Fecal occult blood testing
      was positive in only two (29%) subjects; upper endoscopy revealed erosive
      esophagitis and gastric arteriovenous malformations. Twelve of the 19 (63%)
      premenopausal women with IDA were not diagnosed to have a gynecological source of
      anemia by a specialist in that field. Fecal occult blood testing was negative
      among all women tested and the only digestive complaint was heartburn (pyrosis)
      in seven. Each was identified to have esophagitis, duodenal ulcer, or gastritis
      by upper endoscopy. Colonoscopic examination of the 12 subjects without
      gynecologic etiology for IDA revealed pan colitis (one), diverticulosis (one),
      diverticulosis and melanosis coli (one), hyperplastic polyps (one), and nodular
      lymphoid aggregates (one). CONCLUSIONS: Significant upper gastrointestinal
      disease is identifiable among most premenopausal women with IDA (18 of 19 or
      95%), even when careful evaluation by a specialist in gynecology suggests a
      gynecological source. Upper endoscopy should be considered in the evaluation of
      all premenopausal women with IDA expressing digestive complaints or in those with
      IDA refractory to iron supplementation. Lower endoscopic examination may be
      reserved for those women with symptoms or signs suggestive of colorectal
      disorders.

PMID- 9934741
TI  - Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric
      sensorial responses.
AB  - OBJECTIVE: Therapeutic trials in functional dyspepsia consistently show a
      substantial placebo response, but there is no clear explanation for such an
      effect. Our aim was to evaluate symptomatic, gastrointestinal motor, and gastric
      sensorial responses to placebo treatment in patients with chronic and severe
      functional dyspepsia who were part of a therapeutic trial. METHODS: Thirty
      patients were treated during 8 wk with placebo (white-colored 8-mm tablets
      containing cellulose) by mouth, 20 min before breakfast, lunch, and dinner. We
      quantified the symptomatic response to placebo as a change in global health
      status, and also as a change in the individual and combined (global symptom
      index) of a five-symptom complex: upper abdominal pain, nausea, vomiting,
      bloating/fullness, and early satiety. Gastroduodenal motility, during fasting and
      postprandially, was evaluated by manometry in all patients pretreatment and in 17
      patients posttreatment. Gastric sensitivity to distension was evaluated in 18
      patients pretreatment and in five patients posttreatment (all of them clinical
      responders). RESULTS: Placebo treatment produced a striking symptomatic
      improvement; by 8 wk 80% of the patients reported an improved global health
      status and their global symptom index markedly decreased (23.9+/-1.3 pretreatment
      vs 9.1+/-1.2; p < 0.05). Placebo increased the number of gastric phases III
      starting in the antrum during the fasting period (1.1+/-0.1 vs 1.6+/-0.2; p <
      0.05). As a group, no significant changes in postprandial gastroduodenal motility
      were observed after placebo treatment. However, after placebo a significant
      improvement in the antral motility index (MI) was observed in the subset of
      patients with antral hypomotility (MI pretreatment: 7.9+/-1.0; MI posttreatment:
      11.7+/-0.4; p < 0.05). Before placebo treatment, patients with functional
      dyspepsia showed increased sensitivity to stepwise distension of the stomach
      relative to healthy individuals. After 8 wk of placebo treatment sensitivity to
      distension remained unchanged, even though patients' clinical status was markedly
      improved. CONCLUSION: In patients with functional dyspepsia, the symptomatic
      response to placebo is substantial. Some significant changes were also observed
      in gastric motility: increase in the gastric phase III number as well as in the
      postprandial antral motility index in those with hypomotility pretreatment.
      Remarkably, however, clinical improvement seems to occur independently of
      detectable changes in gastroduodenal motor activity or gastric hypersensitivity
      to distension.

PMID- 9934742
TI  - Descending perineum syndrome: audit of clinical and laboratory features and
      outcome of pelvic floor retraining.
AB  - OBJECTIVE: Our aim was to retrospectively analyze the Mayo Clinic experience of
      descending perineum syndrome from 1987-1997. METHODS: Clinical records were
      abstracted for demographic features, risk factors, results of anorectal and
      defecation tests, and a mailed questionnaire evaluated outcome and current
      symptoms. RESULTS: All results are mean +/- SD. Clinically, 39 patients (38
      women, one man), mean age 53+/-14 yr, presented with constipation (97%),
      incomplete rectal evacuation (92%), excessive straining (97%), digital rectal
      evacuation (38%), and fecal incontinence (15%). Laboratory tests showed anal
      sphincter resting pressure was 54+/-26 mm Hg, and squeeze pressure was 96+/-35 mm
      Hg; expulsion from the rectum of a 50-ml balloon required > 200 g added weight in
      27%; perineal descent was 4.4+/-1 cm (normal < 4 cm) by scintigraphy.
      Scintigraphic evacuation, rectoanal angle change during defecation, and perineal
      descent were abnormal in 23%, 57%, and 78% of the patients, respectively.
      Associated features included female gender (96%), multiparity with vaginal
      delivery (55%), hysterectomy or cystocele/rectocele repair (74%). On follow-up,
      64% responded; 17 of these 25 responders underwent pelvic floor retraining. At 2
      yr median follow-up (range, 1-6 yr), 12 still experienced constipation or
      excessive straining; their perineal descent was greater than in patients who
      responded to retraining (p = 0.005). CONCLUSIONS: Descending perineum syndrome is
      identifiable by clinical history and examination, and the most prevalent
      abnormality on testing is perineal descent > 4 cm; rectal balloon expulsion is an
      insensitive screening test for descending perineum syndrome. Pelvic floor
      retraining is a suboptimal treatment for this chronic disorder of rectal
      evacuation; the extent of perineal descent appears to be a useful predictor of
      response to retraining.

PMID- 9934743
TI  - Symptoms and physiology in severe chronic constipation.
AB  - OBJECTIVE: Symptoms of constipation have been attributed to slow colon transit,
      irritable bowel syndrome (IBS), or pelvic floor dysfunction (PFD). Our aim was to
      determine the existence of symptom-based constipation subgroups and whether these
      correspond to differences in colonic transit and anorectal sensorimotor function.
      METHODS: Constipated patients (n = 108) completed questionnaires, and underwent
      colon transit studies, anorectal manometry, and rectal sensory testing. Factor
      analysis of symptoms was performed. Factor-based symptom scores were correlated
      with physiological findings. RESULTS: Three symptom factors were identified as
      compatible with slow colonic transit, IBS, and PFD. There was a significant
      correlation between the symptoms of slow transit and total and rectosigmoid colon
      transit. There were also significant correlations between both the IBS symptom
      score and the number of Manning criteria with measures of rectal hypersensitivity
      typical of IBS. Neither PFD symptom scores nor symptoms of straining correlated
      with any electromyographic or manometric measure of anal defecatory function or
      with rectosigmoid colon transit. Based on physiological testing patients were
      classified as slow transit, visceral hypersensitivity (typical of IBS), PFD, or
      no abnormalities found. As expected, slow-transit patients had symptoms of
      infrequent stools and patients with visceral hypersensitivity had an increased
      number of Manning criteria for IBS. Patients with PFD physiology and those with
      no detectable abnormalities had no specific symptoms. CONCLUSIONS: Three symptom
      based subgroups for constipation were confirmed: slow transit, IBS, and PFD. Slow
      transit and IBS symptoms correlated with expected physiology. Conversely, PFD
      symptoms and physiology did not correlate.

PMID- 9934744
TI  - In vitro evaluation of integrity and sterilization of single-use argon beam
      plasma coagulation probes.
AB  - OBJECTIVE: Argon plasma coagulation probes (APC) are currently marketed in the
      United States as single-use items, and may constitute a significant per-procedure
      expense. It is unknown whether these probes can be sterilized after endoscopic
      use and if electrical integrity can be maintained after reprocessing. METHODS:
      Ten probes (2.3 mm diameter, 220 cm length) manufactured by ERBE Inc., (Marietta,
      GA) were studied using the ERBE APC 300 at 60 watts. Baseline coagulation depth
      was measured by coagulating a piece of beefsteak for 60 s. Probes were
      contaminated with 10(6) Bacillus subtilis spores, cultured, and manually cleaned.
      Culturing involved introducing 10 cc sterile water through the probes; water was
      filtered, plated onto blood agar, and incubated for 48 h. After ethylene oxide
      (ETO), the probes were cultured to determine sterilization. Finally, the per
      procedure cost of each probe was assessed. RESULTS: Ten of 10 probes completed 10
      testing sessions. One probe split at the proximal end but remained functionally
      intact. Electrical integrity remained intact for all 10 sessions. All probes grew
      too numerous to count colonies of B. subtilis after inoculation and no B.
      subtilis was detected after ETO sterilization. Assuming 10 uses clinically, a
      total per-procedure equipment cost would approximate $24.00, whereas per
      procedure probe cost would equal $42.66 if only five uses were obtained in vivo.
      CONCLUSIONS: The combination of manual cleaning and ETO sterilization
      consistently sterilized APC probes. Ninety percent of the probes showed no sign
      of physical deterioration and 100% maintained their electrical activity after 10
      uses. APC probes can potentially be safely and effectively reused up to 10 times,
      and a significant procedural savings is possible with reuse.

PMID- 9934745
TI  - ERCP in post-Billroth II gastrectomy patients: emphasis on technique.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) in post-Billroth
      II (BII) gastrectomy is more difficult due to anatomical changes. The
      difficulties include entrance to the afferent loop and selective cannulation. Our
      aim here is to report the success rate and special manipulations and techniques
      of this procedure. METHODS: A retrospective review of 56 ERCP procedures in post
      BII gastrectomy patients was performed. There were 43 male and 13 female patients
      with a mean age of 63 yr (range, 32-78 yr). All cases were tried with forward
      viewing endoscope first. Of the failed cases, 10 were retried by side-view
      duodenoscope. The entrance to the afferent loop was attempted by starting from
      the upper opening at the anastomosis site and, if this failed, then using the
      lower opening; presence of bile; and air-contrasted afferent loop under
      fluoroscopy. If failure of afferent loop entrance resulted, hand compression over
      the mid-abdomen, or polypectomy snare in the working channel of the endoscope,
      was tried. For failure of common bile duct cannulation with straight catheters,
      techniques of pushing the catheter against the duodenal wall and bending the tip
      of the endoscope or guidewire were used. RESULTS: The success rate of afferent
      loop entrance was 76.7% (43 of 56 cases). The afferent loop was identified in the
      upper orifice of the anastomosis in 93% (40 of 43) of the cases. Eight cases of
      afferent loop entrance could be facilitated by hand compression, and three by
      polypectomy snare in the working channel of the endoscope. The success rate of
      ERCP cannulation in those successful afferent loop intubation cases was 81.3%
      (35/43 cases). Most of the selective common bile duct (CBD) cannulation was
      achieved by straight (new) catheter and an additional six cases were successful
      using the techniques mentioned. No serious complications were encountered, except
      three cases of submucosal hemorrhage. CONCLUSION: The overall success rate of BII
      ERCP was 62.5% (35 of 56 cases). The special manipulations mentioned in BII ERCP
      can be helpful in certain cases.

PMID- 9934746
TI  - Risk factors for biliary tract cancers.
AB  - OBJECTIVE: Little is known regarding risk factors for biliary tract cancer, i.e.,
      gallbladder carcinoma and extrahepatic bile duct carcinoma. This is the first
      case-control study conducted in the U.S. regarding risk factors for these
      cancers. METHODS: In this hospital-based case-control study, we reviewed the
      medical records of 69 patients with primary biliary tract cancer who were
      admitted to Columbia-Presbyterian Medical Center for surgery between January 1,
      1980, and April 4, 1994, and of 138 controls, consisting of patients admitted for
      surgery for benign conditions. RESULTS: We found a significant association
      between cholelithiasis and biliary tract cancers (odds ratio, 19.5; 95%
      confidence interval, 6.4-59.4). Risk factors associated with gallbladder cancer
      included female gender, age, cigarette smoking, and postmenopausal status in
      women. Risk factors associated with extrahepatic bile duct cancer included
      history of cholecystectomy and hysterectomy in women. CONCLUSION: The risk
      factors for biliary tract cancers that have been identified in our study
      delineate a high-risk population, which in the future may be targeted for
      preventive measures.

PMID- 9934747
TI  - Gallstone disease in high-altitude Peruvian rural populations.
AB  - OBJECTIVE: Cholelithiasis is a common problem in hospitals of the Peruvian Andes;
      however, its prevalence in Andean communities is unknown. To estimate the
      prevalence of gallstone disease in this locale, we conducted a cross-sectional
      community study in three high-altitude Peruvian rural villages (i.e., > 3000 m
      above sea level). METHODS: We examined 911 volunteers > 15 yr of age from three
      villages for gallstone disease by history and ultrasonography. Risk factors for
      gallstone disease were examined in 382 volunteers from one village. RESULTS: The
      age-adjusted prevalence of gallstone disease ranged from 4-10% in men and from 18
      20% in women. Women had significantly higher age-adjusted prevalence rates than
      did men. The prevalence of gallstone disease increased significantly with age and
      decreased significantly with alcohol consumption. Although not statistically
      significant, we found a positive association between gallstone disease and body
      mass index. CONCLUSION: The results of this study indicate that gallstone
      disease, commonly perceived as a disease of the developed world, is also a common
      problem in high-altitude Peruvian communities.

PMID- 9934748
TI  - Comparison of clinical features and liver histology in hepatitis C-positive
      dialysis patients and renal transplant recipients.
AB  - OBJECTIVE: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal
      disease (ESRD) patients before or after renal transplantation were compared to
      study the effect of transplant-related immunosuppression. METHODS: In this
      prospective study all patients on the active transplant list and all patients
      with functioning renal transplants at our hospital were tested for HCV antibody
      (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain
      reaction in most patients. All HCV-positive patients were asked to undergo liver
      biopsy without regard to serum transaminase levels. Patients were interviewed,
      examined, and had detailed chart review. By protocol, liver histology was
      evaluated according to stage and inflammatory activity in a blinded fashion.
      RESULTS: There were 129 HCV-antibody-positive patients, of 795 tested. Sixty
      seven agreed to liver biopsy. Of these, 22 patients had never been transplanted
      and 45 had received transplants. Mean transplant duration before biopsy was 41.2
      months (range, 1-204 months). Transplant patients had significantly longer
      duration of ESRD and estimated duration of HCV infection than patients not
      transplanted. Dialysis patients had significantly more portal inflammatory
      activity and lymphoid follicles on biopsy whereas transplant patients had more
      piecemeal necrosis and steatosis. However, the total histological activity score
      and stage were similar between groups. Multivariate analysis confirmed the
      association between transplant and steatosis. But independent variables including
      transplant duration, HCV infection duration, and ESRD duration were not
      correlated with histological findings. CONCLUSION: Renal transplantation may not
      be associated with an increased risk of progressive liver disease in HCV-positive
      patients, compared with ESRD patients receiving chronic dialysis. Long-term
      studies with serial liver biopsies are needed to resolve this issue.

PMID- 9934749
TI  - Randomized controlled trial of lymphoblastoid interferon alpha for chronic
      hepatitis C (comparison of 9-MU and 6-MU doses). IFN Treatment Group of
      Affiliated Hospitals of the Third Department of Internal Medicine at Nagoya
      University School of Medicine.
AB  - OBJECTIVE: We conducted a randomized controlled trial to compare the efficacy of
      two different dosages of lymphoblastoid interferon alpha (IFN) for the treatment
      of chronic hepatitis C. METHODS: Eighty-four patients with chronic hepatitis C
      were enrolled and randomly assigned into the two groups; group A was treated with
      6 million units (MU) and group B with 9 MU daily for the first 2 wk, and then
      thrice weekly for an additional 14 or 22 wk. RESULTS: Eighty patients were
      evaluated (39 patients in group A and 41 in group B); 14 patients in group A
      (35.9%) and 15 in group B (36.6%) obtained sustained response. The percentages of
      patients who became negative for HCV RNA at the end of the second wk differed
      slightly between the groups, without statistical significance (56.4% and 68.3%).
      When assessed in detail, patients with genotype 1 and < 1 Meq/ml of viral load
      became negative for HCV RNA significantly more frequently in group B (eight of
      eight) than in group A (three of seven) (p < 0.05) at the end of the second week,
      whereas the sustained response rate was similar between the groups (five of eight
      and four of seven). Predictors of sustained response by multivariate analysis
      were low viral load (< 1.0 Meq/ml) and negativity of HCV RNA at the end of the
      second wk of IFN. CONCLUSIONS: The results indicated that there was no difference
      in sustained response rate between the 6-MU and 9-MU doses. The earlier
      disappearance of HCV RNA, at the end of the second wk or at least by the end of
      the fourth week, is an essential condition for sustained response.

PMID- 9934751
TI  - Immunohistochemical evaluation of Bcl-2 gene family expression in liver of
      hepatitis C and cirrhotic patients: a novel mechanism to explain the high
      incidence of hepatocarcinoma in cirrhotics.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is an
      increase in expression of bcl-2 and related bcl-2 gene family members bcl-X and
      bax in liver biopsy samples obtained from patients with either hepatitis C
      infection or cirrhosis. Bcl-2, bcl-X, and bax, as well as other bcl-2-related
      proteins, function coordinately through homo- and heterodimerization to regulate
      apoptosis. Bcl-2, which is characterized as an antiapoptotic, also functions as
      an antioxidant. We hypothesized that a mechanism that could account for increased
      hepatocellular carcinoma in patients with hepatitis C and cirrhosis is selection
      of bcl-2 expressing cells. This selection would be due to the capacity of
      individual cells to resist the toxic effects of inflammatory byproducts,
      specifically reactive oxygen species. METHODS: Sections cut from archived liver
      biopsy samples embedded in paraffin were probed with antibody specific for bcl-2,
      bcl-X, or bax. Liver samples were from normal (N = 5), hepatitis C patients (N =
      19), and cirrhotics (N = 10). Percent positive staining and intensity of staining
      were judged independently for hepatocytes, bile ducts, mononuclear cells, and
      Kupffer cells. RESULTS: Bcl-2 expression was evident in bile ducts and
      mononuclear cells of hepatitis C patients, but was not commonly present in
      hepatocytes (two of 10). In the cirrhotic liver, bcl-2 expression was also
      detected in bile ducts and mononuclear cells, but in contrast to hepatitis
      patients was also expressed in hepatocytes (nine of 10). A similar pattern of
      expression was evident for bcl-X, but in general the level of expression was
      limited relative to that of bcl-2. Bax expression was infrequently present in
      sections from any of the three patient groups. CONCLUSIONS: The data indicate
      that bcl-2 expression is elevated in the liver of cirrhotics, but is not evident
      in the liver of hepatitis C patients. This increase in expression of bcl-2 in
      cirrhotic patients may correlate with development of hepatocellular carcinoma
      given the anti-apoptotic/oncogenic potential of bcl-2.

PMID- 9934750
TI  - Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of
      patients with liver cirrhosis.
AB  - OBJECTIVE: Nitric oxide has been proposed as a mediator of hyperdynamic
      circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric
      oxide. The aim of this study was to investigate the relationship between
      endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to
      correlate these findings with clinical, biochemical, and hemodynamic parameters.
      METHODS: Clinical, biochemical, and hemodynamic parameters were assessed in 66
      patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma
      renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6,
      tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined.
      RESULTS: Mean arterial pressure was lower and interleukin-6, tumor necrosis
      factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were
      higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure
      decreased and interleukin-6 levels increased with worsening of Child score (p <
      0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis
      factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01).
      Elevated levels of interleukin-6 were found in patients with encephalopathy grade
      I, compared with patients without (p < 0.001); this association was independent
      of the severity of liver disease. In patients with low mean arterial pressure,
      interleukin-6 levels were higher than in patients with high mean arterial
      pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites
      levels were not different. By multivariate analysis, high interleukin-6 levels
      showed independent associations with the presence of ascites, encephalopathy, and
      low mean arterial pressure. Only interleukin-6 levels had significant
      correlations with Child score, plasma renin activity, serum and urinary sodium,
      and mean arterial pressure (r > or = 0.4, p < 0.005). CONCLUSIONS: Although the
      activity of the nitric oxide pathway is increased in patients with cirrhosis and
      might contribute to the hemodynamic alteration, other factors are involved.
      Interleukin-6, possibly through nitric oxide-independent mechanisms, also might
      play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic
      encephalopathy.

PMID- 9934752
TI  - FECOM: a new artificial stool for evaluating defecation.
AB  - OBJECTIVE: Traditionally, barium paste has been used for performing defecography.
      Because this substance is not stool-like, barium defecography may not accurately
      represent defecatory function. Our aim was to prospectively compare the utility
      of a new artificial stool, "FECOM"--a silicon-filled and barium-coated,
      deformable device the shape and consistency of which mimicked a normal formed
      stool with that of barium paste. METHODS: Defecography was performed after
      placing FECOM or barium paste in a random order in 12 healthy subjects (two men
      and 10 women). We evaluated the changes in anorectal angle, rectal morphology,
      rectal sensation, and the subjects' preference for a "stool-like" device.
      RESULTS: Anorectal angle at rest, during squeeze, cough, and straining were each
      greater with the FECOM when compared with the barium paste (p < 0.006). Anterior
      rectocele (nine), mucosal intussusception (four), and incontinence (three) were
      identified only with barium defecography. Nine (75%) subjects preferred FECOM to
      barium paste (p < 0.001) and reported that expulsion of this device mimicked more
      closely their stools at home (p < 0.05). CONCLUSION: The anorectal angle is
      influenced by the form and consistency of stool material and is lower with barium
      paste. The detection of rectocele, mucosal intussusception, and barium leakage in
      normal subjects during barium defecography questions the significance of these
      findings. FECOM appears to be a realistic alternative to barium paste for
      performing defecography.

PMID- 9934753
TI  - Use of a push enteroscope improves ability to perform total colonoscopy in
      previously unsuccessful attempts at colonoscopy in adult patients.
AB  - OBJECTIVE: Total colonoscopy with use of a standard adult colonoscope can be
      difficult in the presence of a redundant or angulated colon. It is often possible
      to traverse these areas with the use of a thinner, more flexible endoscope. The
      objective of this study was to evaluate the efficacy of completing total
      colonoscopy using a push enteroscope when a standard colonoscope was
      unsuccessful. METHODS: A prospective analysis was performed for 721 consecutive
      colonoscopies attempted by two gastroenterologists. Those patients in whom
      complete colonoscopy was unsuccessful using the standard colonoscope (Olympus CF
      100L) had attempts to complete colonoscopy using the enteroscope (Olympus SIF
      100). The extent of each exam was recorded. Additional pathologic findings
      discovered by the use of the enteroscope and therapeutic interventions performed
      were additionally noted. RESULTS: Colonoscopy using an enteroscope was performed
      in 32 patients with successful total colonoscopy in 22 patients (68.7%).
      Additional pathology was noted in nine patients who had successful complete
      colonoscopy using the enteroscope; adenomatous polyp (n = 5), adenocarcinoma (n =
      1), bleeding source (n = 2), and extent of colitis (n = 1). Total colonoscopy
      rate using standard adult colonoscope was 93.2% (630 of 676) when cases with poor
      bowel preparation (n = 23) and obstructing lesions (n = 14) were excluded. When
      the results of successful colonoscopies with the enteroscope were included, the
      overall completion rate of total colonoscopy improved to 96.4% (652 of 676).
      CONCLUSION: The use of the enteroscope to help evaluate patients who have had
      incomplete colonoscopies with the standard colonoscope increases the diagnostic
      yield of colonic examination.

PMID- 9934754
TI  - Cancer and adenomatous polyp distribution in the colorectum.
AB  - OBJECTIVE: To examine the possible role of adenomatous polyps in colorectal
      cancer development, this study focused on the relationship of the distribution
      between adenomatous polyps and cancer in the colorectum. METHODS: The
      distribution of 753 adenomatous polyps was compared with that of 35 colorectal
      cancer lesions in 510 male patients ranging from 45 to 55 yr of age who underwent
      a total colonoscopy. RESULTS: The incidence of cancer significantly increased
      with a distal shift in the colorectal sites in comparison with that of
      adenomatous polyps (p < 0.02). CONCLUSION: The different distribution between
      adenomatous polyps and cancer thus suggested that adenomatous polyps at various
      colorectal sites appear to have a different malignant potential for cancer
      development.

PMID- 9934755
TI  - The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic
      polyps. Polyp Prevention Study Group.
AB  - OBJECTIVE: Studies of tandem colonoscopies have reported that 15-25% of
      neoplastic polyps <1 cm in size and 0-6% of larger polyps are overlooked at the
      time of colonoscopy. We determined the miss rate and "true" 1-yr recurrence of
      neoplastic polyps in a population of patients reflecting a broad spectrum of
      different gastroenterology practice settings. METHODS: Patient data from several
      sources were examined for repeat colonoscopies performed on the same patient
      within 120 days of each other. Examination pairs were included for analysis if
      both colonoscopies had good preps and reached the cecum. The miss rate was
      calculated by two methods: 1) a pooled rate, the total number of polyps on all
      second examinations divided by the total number on both examinations, and 2) a
      within-person rate, the average of the individual miss-rates. We estimated a
      "true" 1-yr recurrence rate by subtracting the proportion of patients with a
      missed neoplastic polyp from the proportion of patients with a neoplastic polyp
      found at 1 yr. RESULTS: A total of 76 colonoscopy pairs a mean 47 days apart
      (range, 1-119 days) were identified from a total of approximately 15,000
      examinations and used to calculate the overall miss rates. For the category "all
      polyps" (neoplastic and nonneoplastic polyps), 17% by the pooled method and 11%
      by the within-person method were missed. The corresponding rates for neoplastic
      polyps were 12% by the pooled method and 8% by the within-person method. A total
      of 17% of patients had one or more neoplastic polyps missed on the initial
      examination. The observed 1-yr recurrence rate was determined from 1,314
      colonoscopy pairs performed a mean of 379 days apart and found to be 28% for
      neoplastic polyps. By comparing this to the proportion of patients with one or
      more missed neoplastic polyps, we found the true 1-yr recurrence of neoplastic
      polyps to be 11%. CONCLUSION: There is a significant colonoscopic miss rate for
      neoplastic polyps and "all polyps" in clinical practice that is comparable to
      that previously stated in special research settings. The within-person rate more
      accurately reflects the true colorectal polyp miss rate for any given
      colonoscopic exam than does the pooled rate. The difference between the observed
      1-yr recurrence rate and the proportion of patients with a missed polyp
      represents the true 1-yr recurrence of neoplastic polyps.

PMID- 9934756
TI  - Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver
      damage.
AB  - OBJECTIVE: Only 30% of alcoholics develop cirrhosis, suggesting that the
      development of alcohol-induced liver injury requires one or more additional
      factors. Animal studies have shown that gut-derived endotoxin is one such factor.
      Because increased intestinal permeability has been shown to cause endotoxemia, we
      hypothesized that increased gastrointestinal permeability contributes to the
      pathogenesis of alcoholic liver disease. This study aimed to measure
      gastroduodenal and intestinal permeability in alcoholics with and without chronic
      liver disease and in nonalcoholic subjects with chronic liver disease. METHODS:
      Gastroduodenal permeability was assessed by measurement of urinary excretion of
      sucrose after oral administration. Intestinal permeability was assessed by
      measurement of urinary lactulose and mannitol after oral administration of these
      sugars. RESULTS: Alcoholics with no liver disease showed a small but significant
      increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated
      a marked and highly significant increase in urinary sucrose excretion relative to
      the controls, to the alcoholics with no liver disease, and to the nonalcoholics
      with liver disease. Alcoholics with chronic liver disease demonstrated a marked
      and highly significant increase in both lactulose absorption and in the urinary
      lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In
      contrast, alcoholics with no liver disease and nonalcoholics with liver disease
      showed normal lactulose absorption and normal lactulose/mannitol ratio.
      CONCLUSION: Because only the alcoholics with chronic liver disease had increased
      intestinal permeability, we conclude that a "leaky" gut may be a necessary
      cofactor for the development of chronic liver injury in heavy drinkers.

PMID- 9934757
TI  - Failure of activated charcoal to reduce the release of gases produced by the
      colonic flora.
AB  - OBJECTIVE: Activated charcoal is used to treat excessive volume or malodor of
      intestinal gas. Our previous studies demonstrated that activated charcoal failed
      to bind appreciable quantities of the volumetrically important gut gases.
      However, the odor of feces and flatus derives primarily from trace quantities of
      sulfur-containing gases, primarily H2S and methanethiol, which should avidly bind
      to activated charcoal. The goal of this study was to determine if ingestion of
      activated charcoal reduces the fecal release of sulfur gases. METHODS: Five
      healthy human volunteers ingested 0.52 g of activated charcoal four times daily
      for 1 wk and the fecal liberation of intestinal gases was measured before and
      after the activated charcoal treatment. In an effort to explain the in vivo
      results, additional in vitro studies were performed to compare the binding
      capacity of charcoal to the sulfur gas released by feces. RESULTS: Ingestion of
      activated charcoal produced no significant reduction in the fecal release of any
      of the sulfur-containing gases, nor was total fecal gas release or abdominal
      symptoms significantly influenced. In vitro studies suggested that the failure of
      ingested charcoal to reduce liberation of sulfur gases probably is explained by
      the saturation of charcoal binding sites during passage through the gut.
      CONCLUSION: Commonly employed doses of activated charcoal do not appreciably
      influence the liberation of fecal gases.

PMID- 9934758
TI  - Proinflammatory cytokines in early assessment of the prognosis of acute
      pancreatitis.
AB  - OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of acute
      pancreatitis. The value of serum levels of tumor necrosis factor-alpha,
      interleukin-1-beta, interleukin-6, and interleukin-8 in predicting the outcome of
      acute pancreatitis was evaluated. METHODS: In 50 patients with acute
      pancreatitis, the serum concentrations of tumor necrosis factor-alpha,
      interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein were
      determined on days 1, 2, 3, 4, and 7 after admission. Acute Physiology and
      Chronic Health Evaluation (APACHE II) scores were recorded on days 1, 2, and 3.
      RESULTS: Serum concentrations of interleukin-1-beta, interleukin-6, interleukin
      8, and C-reactive protein on days 1-7 were significantly higher in patients with
      severe pancreatitis than in patients with mild pancreatitis. Patients with severe
      attacks had significantly elevated serum tumor necrosis factor-alpha
      concentrations on days 1-3 compared with those with mild attacks, but not on days
      4 and 7. The median peak value of tumor necrosis factor-alpha, interleukin-1
      beta, interleukin-6, and interleukin-8 was reached on day 1, in contrast to the
      median peak of C-reactive protein, which was reached on day 2. Using cutoff
      levels of 12 pg/ml for tumor necrosis factor-alpha, 1 pg/ml for interleukin-1
      beta, 400 pg/ml for interleukin-6, 100 pg/ml for interleukin-8, 12 mg/dl for C
      reactive protein, and 10 for the Acute Physiology and Chronic Health Evaluation
      (APACHE II) score, the accuracy rates for detecting severe pancreatitis were 72%,
      82%, 88%, 74%, 80%, and 72%, respectively, on day 1 and 78%, 74%, 80%, 76%, 80%,
      and 78%, respectively, on day 2. CONCLUSION: Among the proinflammatory cytokines,
      interleukin-6 is the most useful parameter for early prediction of the prognosis
      of acute pancreatitis.

PMID- 9934759
TI  - Role of immunosuppressive therapy in refractory sprue-like disease.
AB  - Patients with malabsorption and histological findings consistent with celiac
      disease, who are unresponsive to gluten free diet, and in whom other causes of
      flat mucosa have been excluded, are considered to suffer from so called
      unclassified or refractory sprue. Although the true nature of this condition
      needs to be further elucidated, it is known to represent a difficult
      therapeutical problem with potentially fatal course. Herein, we report a patient
      with refractory sprue-like disease who after failing to respond to
      corticosteroids and TPN was in a critical condition. He responded promptly to
      cyclosporine and made a remarkable recovery. In contrast to previous reports, the
      cyclosporine treatment in this patient was pursued only for 1 month, whereupon
      the patient turned responsive to steroids. Subsequent treatment with azathioprine
      allowed corticosteroids to be reduced to a low maintenance dose and eventually
      all drugs could be discontinued without reappearance of symptoms. Cyclosporine
      therapy might be lifesaving in occasional patients with refractory sprue-like
      disease and it may result in reversal of steroid resistance. Moreover,
      azathioprine seems to have a steroid sparing effect in this setting. Short term
      immunosuppressive treatment may have an advantage of lower risk for drug related
      side effects.

PMID- 9934760
TI  - Extraintestinal non-Hodgkin's lymphoma presenting as obstructive jaundice in a
      patient with Crohn's disease.
AB  - We report the case of a 58-yr-old woman, previously diagnosed with Crohn's
      disease of the duodenum, who presented with jaundice and an epigastric mass.
      Diagnostic studies revealed an extraintestinal non-Hodgkin's lymphoma located
      near the head of the pancreas and causing obstructive jaundice. A review of the
      literature indicates the rarity of this association. We discuss the etiology,
      pathogenesis, and management of extraintestinal lymphomas in patients with
      Crohn's disease.

PMID- 9934761
TI  - A stone in a grossly dilated cystic duct stump: a rare cause of
      postcholecystectomy pain.
AB  - We describe the unusual case of a patient who developed recurrent right upper
      quadrant pain 25 yr after cholecystectomy. A cystic lesion containing a calculus
      was identified on transabdominal ultrasound, initially suggesting the possibility
      of gallbladder duplication. Endoscopic retrograde cholangiography identified this
      lesion as a massively dilated cystic duct stump. Surgical resection led to
      complete resolution of symptoms. Recurrent cholelithiasis involving the cystic
      duct stump may lead to massive dilatation, and must be considered in the
      differential diagnosis of postcholecystectomy syndrome.

PMID- 9934762
TI  - Severe gastrointestinal hemorrhage due to Mycobacterium avium complex in a
      patient receiving immunosuppressive therapy.
AB  - Intense immunosuppressive therapy is used frequently for treatment of systemic
      vasculitides, collagenoses, rapidly progressive glomerulonephritis, and after
      organ transplantation. Numerous serious treatment-related side effects include
      localized or disseminated opportunistic infections, and require careful
      monitoring of immunosuppressed patients. Gastrointestinal infections with
      Mycobacterium avium complex (MAC) or other nontuberculous mycobacteria have been
      previously identified in HIV seropositive patients only. We now report the first
      case of an HIV seronegative patient who received immunosuppressive therapy for
      rapidly progressive glomerulonephritis. The patient presented with severe lower
      gastrointestinal bleeding and was diagnosed to have ulcerative colitis due to
      infection with MAC. The patient recovered promptly after administration of
      antimycobacterial therapy. MAC infection should be included in the differential
      diagnosis of gastrointestinal bleeding in all immunodeficient patients. The
      significance of repeated colonoscopy to obtain multiple biopsy specimens with
      histological examination for foam cells and specific staining for acid-fast
      organisms is emphasized.

PMID- 9934763
TI  - Ascites and severe hepatitis complicating Epstein-Barr infection.
AB  - Epstein-Barr (EB) virus infection is common, with up to 90% of individuals
      demonstrating positive titers by age 20. Although elevated liver function tests
      commonly occur, severe hepatitis is rare. Only six cases of ascites complicating
      Epstein-Barr infection are reported, but none clearly demonstrate the absence of
      other causes of hepatic dysfunction. A 37-yr-old male presented with a 4-wk
      history of upper respiratory tract symptoms. Over 3 days before admission he
      developed jaundice and right upper quadrant pain. After hospitalization, the
      patient developed tense ascites requiring paracentesis. Serum-ascitic albumin
      gradient was 0.3 g/dL. Liver function tests peaked at the following values:
      prothrombin time of 24.5 s, total bilirubin of 18.0 mg/dL, and transaminases in
      excess of 5000 IU/L. EB Virus IgG and IgM titers were 1:640 and >1:40,
      respectively. Other viral serologies and polymerase chain reactions were
      negative. The patient experienced a complete clinical and laboratory recovery
      over the next 6 months. This represents the first documentation of ascites
      complicating Epstein-Barr infection without other sources of hepatic dysfunction.
      It demonstrates a narrow serum-ascitic albumin gradient in these patients, and
      that complete recovery can occur with supportive care.

PMID- 9934764
TI  - Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis.
AB  - Autoimmune hepatitis is a form of chronic liver disease characterized by
      progressive hepatocellular inflammation, which usually responds to treatment with
      corticosteroids. However, 10% of patients with autoimmune hepatitis are
      refractory to corticosteroids and develop progressive liver disease and
      cirrhosis. We describe five patients with autoimmune hepatitis who did not
      respond to conventional corticosteroids and azathioprine therapy who were then
      treated with cyclosporine A. Cyclosporine A was started at 2-3 mg/kg/day and
      induced biochemical remission in four of five patients within 3 months. One of
      the four responders relapsed within 1 month of discontinuing cyclosporine on two
      occasions. Each time, liver tests promptly normalized after reinitiation of
      cyclosporine. Two responders were managed with cyclosporine alone. The single
      patient who did not respond to cyclosporine developed progressive liver failure,
      underwent orthotopic liver transplantation, and subsequently died of disseminated
      cytomegalovirus infection. Cyclosporine was generally well tolerated and none of
      the patients developed renal insufficiency. These data and review of 11 cases in
      the literature show that cyclosporine can induce remission of liver disease in
      patients with autoimmune hepatitis who are refractory to corticosteroids.

PMID- 9934765
TI  - Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus
      infection.
AB  - A 54-yr-old man with lymphoma and serological evidence of prior hepatitis B virus
      (HBV) infection, with detectable anti-HBc and anti-HBs, was treated with
      intensive chemotherapy. He had reactivation of HBV infection with acute hepatitis
      B manifest by detectable HBsAg and elevated aminotransferase levels >1000 IU/L.
      He was treated with lamivudine 150 mg daily and had prompt resolution of acute
      hepatitis B with return of elevated aminotransferases to normal, and initial loss
      of HBeAg with later loss of HBsAg. Lamivudine was continued during the course of
      further chemotherapy as prophylaxis against repeat HBV reactivation. Lamivudine
      is a nucleoside analogue that is a potent inhibitor of HBV reverse transcriptase
      and HBV replication. Lamivudine therapy should be considered for the treatment of
      HBV reactivation and might play a future role as preemptive therapy of HBV
      reactivation in patients with prior hepatitis B or chronic hepatitis B with
      inactive viral replication.

PMID- 9934766
TI  - Fatal invasive gastric mucormycosis occurring with emphysematous gastritis: case
      report and literature review.
AB  - Emphysematous gastritis is an often lethal, rare clinical entity referring to air
      bubbles in the wall of the stomach produced by gas-forming bacteria. Invasive
      gastrointestinal mucormycosis is an unusual clinical presentation of this
      invasive fungal disease. We report the first case of invasive gastric
      mucormycosis occurring with emphysematous gastritis, and review the literature
      regarding both of these clinical entities.

PMID- 9934767
TI  - Peutz-Jeghers syndrome: molecular analysis of a three-generation kindred with a
      novel defect in the serine threonine kinase gene STK11.
AB  - The Peutz-Jeghers syndrome, phenotypically characterized by mucocutaneous
      pigmentation and hamartomatous polyposis, is an autosomal dominant disease with
      variable expression and incomplete penetrance. Moreover, affected patients are at
      increased risk for gastrointestinal and other malignancies. Recently, a mutated
      gene encoding abnormal forms of the novel serine threonine kinase STK11 has been
      identified as a genetic cause of Peutz-Jeghers syndrome. Here, we report the
      molecular analysis of the STK11 gene in a patient with Peutz-Jeghers syndrome,
      which in exon 1 revealed a guanine (G) insertion in the 5 G repeat of codons 51
      53. The insertion leads to a frameshift with a premature TGA stop codon 324 bp
      downstream in codon 162, predicting the expression of a truncated protein without
      kinase activity. This heterozygous germline mutation was also found in the
      affected father and in one affected sister of the index patient, but not in any
      phenotypically unaffected family member or in unrelated control subjects. In DNA
      isolated from microdissected hamartomatous polyps of the index patient, exon 1 of
      the STK11 gene could not be amplified suggesting that both alleles of STK11 exon
      1 were lost in the hamartomatous polyps. Identification of a STK11 gene mutation
      in an index patient offers the possibility of a predictive diagnosis, and
      initiation of specific screening programs in the genetically affected kindred.

PMID- 9934768
TI  - Fulminant hepatic failure secondary to malignant melanoma: case report and review
      of the literature.
AB  - Malignant melanoma has a propensity to metastasize widely to many organs,
      involving the liver in up to one-third of cases. Fulminant hepatic failure is an
      unusual presentation of hepatic neoplasms, whether primary or metastatic. We
      describe a case of malignant melanoma with liver metastases that rapidly
      progressed to fulminant hepatic failure and death. Striking elevations of liver
      tests, particularly lactate dehydrogenase, were seen. Liver biopsy showed diffuse
      intrasinusoidal infiltration with melanoma cells. In patients with malignant
      melanoma, raised serum lactate dehydrogenase levels may suggest hepatic
      involvement, with extreme elevations possibly predictive of liver failure.

PMID- 9934770
TI  - Adenosquamous carcinoma in Barrett's esophagus presenting as pseudoachalasia.
AB  - A case of pseudoachalasia resulting from adenosquamous carcinoma arising from the
      mucous epithelium of a Barrett's esophagus is presented. This case represents an
      unusual combination of Barrett's esophagus giving rise to an esophageal carcinoma
      with squamous as well as glandular features, rather than the usual adenocarcinoma
      and pseudoachalasia.

PMID- 9934769
TI  - Simultaneous pancreatitis and hepatitis associated with trimethoprim
      sulfamethoxazole.
AB  - A 34-yr-old woman developed simultaneous pancreatitis and hepatitis following
      exposure to trimethoprim-sulfamethoxazole (TMP/SMX). The episode occurred 4 yr
      after a previous episode of hepatitis associated with TMP/SMX. This patient
      represents the second case of concurrent TMP/SMX-induced pancreatitis and
      hepatitis reported in the literature. However, it is the first in which the
      adverse reaction was documented following an inadvertent rechallenge with the
      drug.

PMID- 9934771
TI  - Both massive upper and lower gastrointestinal hemorrhage secondary to
      tuberculosis.
AB  - We report a case of gastrointestinal tuberculosis, presenting with both massive
      upper and lower gastrointestinal bleeding that required two emergency operations.
      Massive bleeding is rare in gastrointestinal tuberculosis because of associated
      obliterative endarteritis. Tuberculosis should be considered in the differential
      diagnosis of massive gastrointestinal bleeding in the appropriate clinical
      setting even in an immunocompetent patient.

PMID- 9934772
TI  - Remission of Menetrier's disease after a prolonged period with therapeutic
      eradication of Helicobacter pylori.
AB  - We report here a case of Menetrier's disease (MD) that required a prolonged
      period for remission after eradication therapy of Helicobacter pylori (HP). The
      appropriate time needed to judge the efficacy of the eradication therapy for HP
      infection in an MD case is discussed.

PMID- 9934773
TI  - A case of granulocyte-colony stimulating factor producing gallbladder cancer.
AB  - Ever since the identification of the colony-stimulating factor (CSF), granulocyte
      CSF (G-CSF)-producing tumors have often been reported, and have been attracting
      attention, especially in pulmonary cancer. However, there have been only a small
      number of reports of G-CSF-producing tumors in cases of gastrointestinal cancer,
      and only four cases of G-CSF-producing gallbladder cancer have been reported so
      far. Recently, we encountered a 73-yr-old man with G-CSF-producing gallbladder
      cancer. The leukocyte count in the peripheral blood increased to the maximum of
      75,200/mm3 during the course of observation, and mature neutrophils accounted for
      97% (segmented forms: 89%, band forms: 8%). The serum G-CSF concentration was
      high (129 pg/ml). The leukocyte count became normalized postoperatively, and the
      serum G-CSF concentration also decreased (50 pg/ml). The tumor was diagnosed as
      undifferentiated adenocarcinoma of the pleomorphic type on the histopathologic
      examination. Numerous tumor cells were stained with the anti-G-CSF antibody.
      Detailed findings of the patient are presented here together with some discussion
      of the literature.

PMID- 9934774
TI  - Jejunal schwannoma in neurofibromatosis: an unusual cause of massive
      gastrointestinal bleeding.
AB  - Small intestinal schwannomas are exceedingly rare tumors arising mainly from
      Schwann cells of Auerbach's plexus, and are usually solitary and asymptomatic. We
      report the first case of a jejunal schwannoma causing life-threatening
      gastrointestinal bleeding in a patient with neurofibromatosis.

PMID- 9934775
TI  - Spontaneous splenic rupture in a patient with large hepatocellular carcinoma.
AB  - We report a 61-yr-old woman with acute circulatory failure from spontaneous
      splenic rupture with decompensated liver cirrhosis complicating large
      hepatocellular carcinoma exposed on the right liver surface. On admission, the
      patient was tentatively diagnosed as having rupture of the hepatocellular
      carcinoma, and she died 15 hours after admission despite blood transfusion.
      Autopsy revealed that the origin of the intraperitoneal hemorrhage was a ruptured
      spleen. According to a MEDLINE search of the English-language literature
      published between 1966 and March 1998, this is the first reported case of
      spontaneous splenic rupture in a patient with hepatocellular carcinoma without
      splenic metastasis.

PMID- 9934776
TI  - Successful treatment of an advanced hepatocellular carcinoma with the long-acting
      somatostatin analog lanreotide.
AB  - Treatment options for hepatocellular cancer apart from surgical resection are
      limited because of the drug-refractory nature of this disease. Little is known
      about the role of somatostatin-receptors in hepatocellular cancer, and
      somatostatin analogs have not been investigated for treatment of this malignancy.
      We present the case of a 68-yr-old male, who was successfully treated with the
      long-acting somatostatin analog lanreotide.

PMID- 9934777
TI  - Hemorrhage from recanalized umbilical vein in a patient with cirrhosis.
AB  - The formation of portosystemic collaterals occurs frequently in portal
      hypertension; however, the finding of a patent or recanalized umbilical vein has
      more often been incidental, with only six cases of recanalized umbilical veins or
      patent paraumbilical veins demonstrated with clinical significance This is only
      the second documented case of an umbilical vein with external hemorrhage
      significant enough to cause hemodynamic instability. It raises important
      questions with regard to prognostic indices for rebleeding at the umbilicus as
      well as at other, more common, portosystemic collateral sites.

PMID- 9934778
TI  - Toxic megacolon associated with Campylobacter jejuni colitis.

PMID- 9934780
TI  - Tips for preventing esophageal variceal bleeding.

PMID- 9934779
TI  - Colonic adenocarcinoma presenting as supraclavicular lymphadenopathy in a 26-yr
      old man: a case report.

PMID- 9934781
TI  - Whole-body PET proves superior to CT for staging primary colorectal carcinoma.

PMID- 9934782
TI  - The "joys" of pregnancy?

PMID- 9934783
TI  - Benign cystic teratoma of the lesser omentum.

PMID- 9934784
TI  - Percutaneous management of a broncho-biliary fistula complicating ruptured amebic
      liver abscess.

PMID- 9934785
TI  - Anticardiolipin antibody levels in patients with Budd-Chiari syndrome.

PMID- 9934786
TI  - Quinapril and pancreatitis.

PMID- 9934787
TI  - Re: Zuccaro--practice guidelines.

PMID- 9934788
TI  - Re: McNair et al. Autoimmune hepatitis overlapping with primary sclerosing
      cholangitis.

PMID- 9934789
TI  - Anaphylactic reaction caused by perianal application of glyceryl trinitrate
      ointment.

PMID- 9934790
TI  - An unusual cause of acute intestinal bleeding in a young woman: angiodysplasia
      and Taenia saginata infestation.

PMID- 9934791
TI  - Urinary tuberculosis in a two-year-old boy.
AB  - The authors describe a case of genitourinary tuberculosis hitherto unobserved in
      early childhood.

PMID- 9934792
TI  - Adult Wilms' tumour. A report of two cases and their treatment and prognosis.
AB  - Adult Wilms' tumour, unlike that seen in childhood, is a rare disease. We report
      on two patients of whom one is alive with no evidence of disease at 65 months of
      follow-up and the other had no evidence of disease at 10 months when she was lost
      to follow-up. The literature has been reviewed and the prognosis and treatment
      alternatives are presented.

PMID- 9934793
TI  - Features of primary vesicoureteric reflux detected by investigation of foetal
      hydronephrosis.
AB  - Primary vesicoureteric reflux (VUR) diagnosed on investigation of foetal
      hydronephrosis accounts for many antenatally detected uropathies. In order to
      study foetal VUR and its consequences, newborns with foetal hydronephrosis were
      investigated by ultrasound, micturating cystourethrogram and 99mTechnetium
      dimercapto-succinic acid (DMSA), after beginning of chemoprophylaxis. Twenty
      eight infants with VUR (bilateral in 15 cases) were identified giving a total 43
      renal units for study. There was a predominance of males (86%), moderate/severe
      reflux (84%) and renal damage (51%). Presence of renal damage was correlated with
      the severity of reflux. VUR should be investigated in cases of foetal
      hydronephrosis and our results support that renal damage is frequently congenital
      and not secondary to urinary tract infection.

PMID- 9934794
TI  - Effects of verapamil on bladder instability induced by partial outflow
      obstruction in rat.
AB  - BACKGROUND: Overactivity of the detrusor due to benign prostatic hyperplasia may
      be induced by hyperpermeability of the smooth muscle cell membrane to calcium. We
      investigated the effect of verapamil, a calcium channel blocker, on detrusor
      function in outflow obstructed and control rat bladders. METHODS: Verapamil was
      injected intravenously via a catheter inserted into the internal jugular vein in
      doses of 0.5, 1.0, 2.0, 4.0, and 10.0 mg/kg in rat bladders with and without
      partial outflow obstruction under urethane anaesthesia. The intravesical pressure
      was monitored continuously. We measured the tidal voided urine volume, the
      voiding pressure, the pressure at which micturition was induced, and the end
      point pressure of micturition. RESULTS: The tidal voided urine volume was
      significantly decreased in the obstructed bladders before administration of
      verapamil. Verapamil had similar effects in cystometric parameters in obstructed
      and control bladders. Verapamil increased the tidal voided urine volume, the
      pressure at which micturition was induced, and the end-point pressure of
      micturition, and reduced the voiding in obstructed and control bladders.
      Verapamil at doses of 4.0 mg/kg or higher induced significant arrhythmia.
      CONCLUSIONS: Verapamil reduced the contractile force of the bladder and increased
      the capacity and residual urine volume in both normal and obstructed bladders.
      Thus, although calcium channel blockers such as verapamil may be effective in
      treating a hyperactive bladder, they may have adverse cardiovascular effects.

PMID- 9934795
TI  - Stone fragility in shock wave lithotripsy can be predicted in vitro.
AB  - OBJECTIVE: To investigate the effect of stone size, chemical structure,
      radiologic appearance, stone weight and stone mineral density on in vitro stone
      fragility. METHODS: A total of 216 stones obtained by open surgery were
      stratified according to their size, chemical structure (X-ray crystallography),
      radiologic appearance, mineral content and density (dual photon absorptiometry)
      and weight. Stone fragility was measured by the number of shock waves needed to
      completely fragment the stones in a phantom model by Dornier. RESULTS: Stone
      weight increased according to stone size and mineral density varied in relation
      to chemical composition. The radiologic appearance was not predictive of the
      chemical content. The most significant variable to predict the number of shock
      waves needed for full fragmentation was the stone weight. The stone weight could
      be formulated as a function of mineral content and the equation had statistical
      significance (p = 0.000). The necessary number of shock waves for complete
      disintegration also could be estimated by using stone weight, stone size and
      mineral density. This equation was also statistically significant (p = 0.000).
      CONCLUSIONS: Stone weight which is a function of stone mineral content seems to
      be the single most important parameter to predict stone fragility in vitro. Stone
      weight can be estimated by using the stone mineral content. Prediction of the
      necessary number of shock waves for full fragmentation seems possible and is
      formulated into an equation that proved to be statistically significant in vitro.
      In vivo application of this estimation awaits further research.

PMID- 9934796
TI  - Extraperitoneoscopic ureterocutaneostomy with hernia repair.

PMID- 9934797
TI  - Inflammatory pseudotumour of the bladder: a rare cause of haematuria.

PMID- 9934798
TI  - Bladder cancer in a patient on long-term haemodialysis.
AB  - We report a case of bladder cancer on long-term haemodialysis. The relationship
      between bladder cancer and haemodialysis, and the necessity of periodic cytology
      of bladder washing are discussed.

PMID- 9934799
TI  - Successful chemotherapy in a patient with recurrent carcinoma of the urachus.
AB  - Urachal neoplasm generally has a poor prognosis, because of long latency period,
      extravesical progression and pathological predominant pattern of adenocarcinomas.
      We report a case of recurrent poorly differentiated carcinoma of urachal remnant,
      which responded well to combination systemic chemotherapy (methotrexate,
      vinblastine, doxorubicin and cisplatin: M-VAC). Our case was possibly of
      transitional cell origin. The patient has been symptom-free even 13 months after
      the first chemotherapy course.

PMID- 9934800
TI  - Correlation between Gleason score of needle biopsy and radical prostatectomy
      tissue.
AB  - Gleason score has been identified as an important variable to predict disease
      extent and biologic behaviour of prostate cancer. However, the correlation
      between Gleason score of needle biopsy and surgical specimen is often poor. We
      studied 72 patients who underwent needle biopsy and radical prostatectomy to
      correlate Gleason score with PSA, clinical and pathological tumour stage. Only
      47.2% of Gleason scores were identical in the biopsy and specimens, 37.5% were
      undergraded and 15.2% were overgraded. Correlations between clinical and
      pathological stage were identical in 30.5% of patients, 61.1% of patients were
      understaged and 8.3% overstaged. In conclusion, accuracy of clinical staging and
      grading of prostate cancer is low. Although the Gleason score on needle biopsy
      might be useful to predict the final stage and grade, correlation with surgical
      specimen is poor.

PMID- 9934802
TI  - Age-specific PSA reference ranges in a group of non-urologic patients.
AB  - Age-specific serum PSA reference ranges have recently been proposed to be more
      sensitive in young and more specific in elder patients. However, some conflicting
      results have been reported from different centers. In order to establish age
      specific PSA reference ranges for our country, we measured the serum PSA levels
      of 400 healthy men over 40, between February 1995 and June 1996. Our study
      population consisted of men who had either PSA values lower than 4.0 ng/ml and
      normal digital rectal examination or negative prostatic biopsies taken for any
      reason. IMX assay was used for PSA determination in all patients. Mean PSA values
      and standard deviations for each age group were: 1.7+/-1.1 ng/ml for 40-49 years
      (n = 28), 2.0+/-1.2 ng/ml for 50-59 years (n = 110), 2.9+/-1.7 ng/ml for 60-69
      years (n = 158) and 3.5+/-2.0 ng/ml for 70-79 years (n = 104). We conclude that
      further studies of larger series will lead us to standardize age-specific
      reference ranges in our country and, accordingly, we will be able to select the
      candidates for prostate biopsy more adequately.

PMID- 9934801
TI  - Relationship between prostate specific antigen density, microvessel density and
      prostatic volume in benign prostatic hyperplasia and advanced prostatic
      carcinoma.
AB  - The aim of this study was to investigate the relationship between prostate
      specific antigen density and prostate volume with microvessel density in patients
      with benign prostatic hyperplasia and advanced prostatic carcinoma. Sixty-eight
      patients with benign prostatic hyperplasia and 11 patients with advanced
      prostatic carcinoma participated in the study. The paraffin blocks of all
      patients were stained with CD34 by the standard immunohistochemical technique and
      microvessel density, prostate specific antigen density and prostatic volume were
      determined. In patients with benign prostatic hyperplasia the mean microvessel
      density, mean prostate specific antigen density and mean prostatic volume were
      74+/-89+/-22.73, 0.12+/-0.10 and 59.97+/-27.0 ml, respectively. There was no
      correlation between prostate specific antigen density and mean prostatic volume
      or microvessel density (r = 0.079 and -0.095, respectively). In patients with
      advanced prostatic carcinoma the mean microvessel density, mean prostate specific
      antigen density and mean prostatic volume were 147.90+/-47.55, 0.63+/-0.41 and
      54.00+/-22.42 ml, respectively. In this group, while there was a good correlation
      between prostate specific antigen density and microvessel density (r = 0.785), no
      significant correlation was found between prostatic volume and microvessel
      density (r = -0.07). There was significant statistical difference in patients
      with advanced prostatic carcinoma compared to patients with benign prostatic
      hyperplasia in terms of mean microvessel density (p<0.0001). The findings that
      there was no correlation between prostatic volume and MVD either in benign
      prostatic hyperplasia or in prostatic carcinoma suggest that microvessel
      development is not correlated with prostatic volume but may be correlated with
      morphology.

PMID- 9934804
TI  - Can LDH activity in spermatic vein indicate testicular damage? A preliminary
      report.
AB  - We aimed to investigate the relationship between varicocele and lactic
      dehydrogenase (LDH), an intracellular enzyme that indicates cellular damage. LDH
      levels were measured in the blood samples of 17 oligoasthenospermic infertile
      patients with varicocele which were obtained synchronously from spermatic and
      peripheral veins during operation. Sperm counts ranged from 1 to 74 million/ml,
      while motility ranged from 10% to 60%. LDH level in spermatic vein was found
      statistically higher than the level in peripheral vein (p = 0.042). There was no
      correlation between sperm counts and LDH level in spermatic vein. We found a
      significant increase in spermatic vein LDH level in varicocele. We think that
      further studies are needed to reveal the relationship between spermatic vein LDH
      level and varicocele.

PMID- 9934803
TI  - Treatment of stage I seminoma: should beta-HCG positive seminoma be treated
      aggressively?
AB  - To assess the prognostic value of beta-HCG positive stage I seminoma, clinical
      records of 122 patients with testicular germ cell tumour were reviewed. Fifty
      five patients (mean age 38.7 years) of 122 (45.1%) had stage I seminoma.
      Preorchiectomy beta-HCG level was determined in 54 patients. Twenty-nine patients
      of 54 (53.7%) had elevated preorchiectomy beta-HCG level. No significant
      relationship was found in the rate of locally progressive cancer between beta-HCG
      positive and negative cases. Treatment consisted of radiotherapy after inguinal
      orchiectomy for beta-HCG negative cases, and chemotherapy or radiotherapy for
      beta-HCG positive cases. Tumour recurrence was found in one patient with normal
      beta-HCG level. Our limited series demonstrated that preorchiectomy elevated beta
      HCG had no significant relationship to local tumour invasion or prognostic value.
      Therefore, infradiaphragmatic radiation therapy may be useful for beta-HCG
      positive stage I seminoma.

PMID- 9934805
TI  - Leiomyoma of the female urethra.
AB  - Leiomyoma of the female urethra is an uncommon but benign condition. The authors
      report two additional cases of successfully operated neoplasms. The difficulties
      of the diagnosis, differential diagnosis, the surgical treatment and the
      complications are discussed.

PMID- 9934806
TI  - Non-Hodgkin's lymphoma of the female urethra presenting as a caruncle.
AB  - Primary non-Hodgkin's lymphoma of the female urethra is extremely rare. To our
      knowledge only 10 cases have been reported to date. We present the 11th case in
      the literature.

PMID- 9934808
TI  - Comparison of Alprostadil (Caverject) and a combination of vasoactive drugs as
      local injections for the treatment of erectile dysfunction.
AB  - The efficiency and side effects of a single dose of 20 mcg of intracorporeally
      applied Alprostadil (Caverject, Upjohn), a prostaglandin E1, in inducing penile
      erection were examined in 30 patients. In addition, the effect of this dose of
      prostaglandin E1 was compared to that of 30 mg of papaverine plus 0.5 mg of
      regitine (phentolamine). All patients received a first injection of the
      combination of the vasoactive drugs and a second injection of the prescribed dose
      of Caverject. The degree of erection, time interval between injections and
      achievement of full erection as well as side effects during and after injection
      were compared. All patients had a burning sensation during the injection of
      Caverject. Two patients given the vasoactive combination got priapism and were
      evacuated; this complication was not reported for Caverject. In the doses used
      Caverject was superior to papaverine plus phentolamine in inducing penile
      erection and in achieving a higher grade of erection.

PMID- 9934807
TI  - Sertraline in the treatment of premature ejaculation: a double-blind placebo
      controlled study.
AB  - This study investigated the efficacy and the adverse effects of sertraline in the
      treatment of premature ejaculation (PE). Thirty-seven patients with PE were
      randomly assigned to receive either sertraline or a placebo. Of them 22 were
      given 50 mg of sertraline per day and the other 15 patients were given an
      identical placebo one per day. After 4 weeks, the latency to ejaculation in the
      sertraline group was found to be significantly longer than that of the placebo
      group (p<0.01). None of the patients discontinued therapy due to adverse effects.
      These results indicate that sertraline is an effective therapy for PE.

PMID- 9934809
TI  - Elevated tumour markers in patients with Balkan endemic nephropathy.
AB  - Balkan nephropathy (BEN) is commonly associated with urothelial cancer.
      Urothelial cancer is manifested in the advanced stage of disease. The aim of this
      study was to facilitate early detection of urothelial cancer in BEN patients and
      their family members living in an endemic region by using tumour markers,
      carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and a
      putative marker, ferritin. Fifteen BEN patients with normal renal function, 17
      with renal failure (BEN-RF), 13 healthy members of their families (HFM), 14
      patients with glomerulonephritis (GN) and 12 healthy controls (C) were studied.
      Serum CEA levels in BEN patients were within normal limits, however, in BEN-RF
      patients they were significantly increased over HFM (p<0.05). Serum TPA levels in
      BEN and BEN-RF patients were significantly higher than in the C and HFM groups
      (p<0.05). Urinary CEA was not significantly different between the groups studied.
      Urinary TPA levels in HFM (median 125 U/l, BEN (236 U/l) and BEN-RF (275 U/l)
      were significantly increased over C (30 U/l), however, TPA levels were increased
      also in GN patients (437 U/l). None of the BEN patients studied developed
      urothelial cancer during the ten years' follow-up. Markedly elevated urinary TPA
      like levels in all patients studied (HFM, BEN, BEN-RF, GN) suggest that urinary
      TPA may not be a reliable tumour marker. However, the clinical relevance of high
      TPA levels in BEN patients should be evaluated.

PMID- 9934810
TI  - Experience with kidney transplantation in children and adolescents.
AB  - BACKGROUND: Paediatric kidney transplantation has different aspects in adults in
      terms of underlying primary renal disease, surgical technique, perioperative care
      and graft prognosis. Significant urological problems are present in a high
      percentage of paediatric recipients. This study was undertaken to characterize
      paediatric kidney transplantation as performed at our institutes. METHODS: Twenty
      eight patients (age range 4-17 years, 10 girls, 18 boys) were included in this
      study. We analyzed (1) urologic procedures performed prior to or simultaneously
      with transplantation, (2) intraoperative changes in haemodynamics, (3)
      postoperative complications and (4) acute allograft rejection and graft
      prognosis. RESULTS: Of 4 patients with lower urinary tract abnormalities
      (neurogenic bladder in 3, posterior urethral valve in 1), 2 underwent
      augmentation ileocystoplasty prior to transplantation. The Mitrofanoff procedure
      as a diversion for neourethra was also performed in 2 of the 4 patients. All
      these 4 patients were managed with clean intermittent catheterization. Central
      venous pressure changes before and after graft vessel declamping were much
      greater in patients with body weight below 25 kg than in those above 25 kg. Five
      surgical complications and 6 infections were encountered postoperatively and
      hypertension was lasting in 6. Thirteen patients experienced 19 periods of acute
      allograft rejection. All of the 24 patients in the cyclosporin era (1986-)
      overcame rejections and they are all alive with good graft function. CONCLUSIONS:
      As long as proper pretransplant patient evaluation and management, and intensive
      perioperative care are undertaken, good prognosis of renal allograft can be
      achieved in young patients.

PMID- 9934811
TI  - Renal artery reconstruction in transplant kidney. Case report.
AB  - A 30 years old female patient, to whom a cadaveric kidney transplantation was
      performed 7 years earlier, presented severe hypertension attacks for 2 years.
      Renal artery stenosis diagnosed by angiography, PTA could not be performed. She
      underwent an operation for surgical correction of stenosis and successful
      internal iliac renal artery anastomosis performed by saphenous vein
      interposition. The patient was discharged at the fourteenth postoperative day
      with excellent kidney function and stable blood pressure.

PMID- 9934813
TI  - Is it worth treating diabetes? Lessons from the UKPDS. United Kingdom Prospective
      Diabetes Study.

PMID- 9934812
TI  - The importance of serum transferrin receptor level in the diagnosis of functional
      iron deficiency due to recombinant human erythropoietin treatment in
      haemodialysis patients.
AB  - In haemodialysis (HD) patients, functional iron deficiency frequently appears due
      to recombinant human erythropoietin (r-HuEPO) treatment. However, the diagnosis
      of iron deficiency is not always easy in such patients. Recent studies have shown
      that the serum transferrin receptor (s-TfR) level is a sensitive, quantitative
      measure of tissue iron deficiency. In this study, we examined the changes in s
      TfR levels in patients with iron deficiency anaemia due to r-HuEPO treatment. We
      compared s-TfR levels of 24 patients with i.v. administered r-HuEPO (50-70
      U/kg/dose) at the end of each dialysis session (three times a week) and diagnosed
      as having iron deficiency anaemia by routine laboratory methods (ferritin <50
      microg/l and transferrin saturation <16%) with s-TfR levels of 32 patients not
      receiving r-HuEPO and without iron deficiency anaemia. Also, 40 healthy volunteer
      subjects were included in the study as a control group. Serum ferritin and
      transferrin receptor levels were measured with ELISAs using monoclonal reagents.
      There were no differences between the two groups with and without iron deficiency
      anaemia with respect to mean age, body weight, haemodialysis duration,
      haemoglobin and serum creatinine levels (p>0.05). For s-TfR levels, while no
      difference was present between the control and the non-iron deficiency groups
      (p>0.05), the iron deficiency group had higher s-TfR values than those of both
      the control and non-iron deficiency groups (p<0.001). Besides, there was an
      inverse correlation between haemoglobin and s-TfR levels in patients with iron
      deficiency anaemia (r = -0.85, p<0.0001). We conclude that the measurement of s
      TfR levels may be useful in the diagnosis of functional iron deficiency in
      haemodialysis patients receiving r-HuEPO.

PMID- 9934814
TI  - Anti-insulin antibodies may cause hypoglycaemia following pancreas
      transplantation.
AB  - Some pancreas transplantation (PTX) recipients experience hypoglycaemia after
      transplant. We studied the incidence and pattern of hypoglycaemic symptoms
      following PTX and later studied the glucose and pancreatic hormone response to
      Sustacal in patients with and without hypoglycaemia following PTX. In a survey of
      54 PTX recipients who were 2 to 33 months post-transplant, 29 reported symptoms
      of hypoglycaemia at any time following their transplant. Of 12 patients who tried
      to document their blood glucose during any episode, 5 had a blood glucose less
      than 3.3 mmol/l, and another 5 documented a blood glucose from between 3.33 and
      3.88 mmol/l. The patients reporting symptoms were less likely to be insulin
      resistant with longer time post-PTX, lower body mass index (BMI), and on lower
      doses of prednisone. Later, 12 patients with established, repeated episodes of
      hypoglycaemia following PTX were case-matched to PTX recipients without
      hypoglycaemic symptoms. Fasting glucose, free and total immunoreactive insulin
      (IRI), C-peptide, proinsulin and glucagon were measured following a 4 h Sustacal
      challenge. The hypoglycaemic group was further divided into those whose glucose
      rose after Sustacal (Hypo-High) and those whose blood glucose did not rise from
      baseline concentration (Hypo-Flat). The Hypo-High subgroup had a lower fasting
      free/total IRI ratio in addition to a greater increase in blood glucose after
      Sustacal compared with either Hypo-Flat or non-hypoglycaemic transplant
      recipients. The low free/total insulin ratio and hyperglycaemic response to
      Sustacal are consistent with the presence of anti-insulin antibodies, an
      established cause of hypoglycaemia. In summary, documented hypoglycaemia, while
      uncommon, may occur and be significant following PTX. Anti-insulin antibodies may
      be one of the many factors contributing to hypoglycaemia in this population.

PMID- 9934815
TI  - Post-transplantation hypoglycaemia in type 1 diabetic pancreas allograft
      recipients.
AB  - Physiologic replacement of insulin in patients with type 1 (insulin-dependent)
      diabetes following pancreas allograft transplantation results in normoglycaemia
      during fasting and postprandial states. However, this is achieved at the expense
      of peripheral hyperinsulinaemia in the heterotopic pancreas allograft recipients
      with systemic insulin drainage. In addition, the pancreas allograft is denervated
      and thus devoid of autonomic nervous regulation of pancreatic beta-cell
      secretion. Recent reports of hypoglycaemia (symptomatic and asymptomatic), which
      can be fatal, have raised serious concerns regarding the aetiology of the
      hypoglycaemic epiphenomenon in type 1 diabetic pancreas allograft recipients.
      Although the prevalence of significant hypoglycaemia following pancreas
      transplantation remains unknown, it is important to conduct studies to determine
      the mechanisms, the natural history, predictors and treatment as well as the long
      term prognosis (graft and patient survival rates) of type 1 diabetic patients who
      develop pancreas-allograft-associated hypoglycaemia. Indeed, predictors of
      hypoglycaemia following pancreas allograft could significantly impact on the
      selection of appropriate therapeutic options for pancreas allograft
      transplantation. Finally, whether postpancreas allograft transplantation
      associated hypoglycaemia in type 1 diabetic patients carries greater morbidity
      and mortality when compared to those without hypoglycaemia deserves to be
      investigated.

PMID- 9934816
TI  - Prevention and treatment of hypoglycaemia unawareness in type 1 diabetes
      mellitus.
AB  - Unawareness of hypoglycaemia (reduced ability/failure to recognize hypoglycaemia
      symptoms at the physiological threshold of 3.0 mmol/l) occurs frequently in type
      1 diabetes mellitus, and patients are then at risk for severe hypoglycaemia.
      Unawareness of hypoglycaemia is the result of earlier frequent episodes of
      hypoglycaemia (iatrogenic). Likewise, a history of hypoglycaemia induces
      unawareness, while meticulous prevention of hypoglycaemia can reverse
      hypoglycaemia unawareness. Therefore, it is essential that insulin therapy
      regimens for type 1 diabetes mellitus be designed not only to maintain near
      normoglycaemia, but also to minimize hypoglycaemia. Such a goal is feasible as
      long as (1) a rational plan of insulin therapy is adopted, including appropriate
      use of the short-acting insulin analogue lispro, (2) blood glucose is properly
      monitored, (3) blood glucose targets are individualized, and (4) education
      programs are widely implemented.

PMID- 9934817
TI  - Neuroendocrine peptides of the gastrointestinal tract of an animal model of human
      type 2 diabetes mellitus.
AB  - We studied ten obese diabetic mice (Umea/ Bom-ob) and 10 homozygous lean controls
      aged 21 weeks. The concentration of several neuroendocrine peptides was
      determined by radioimmunoassay of tissue extracts of antrum, duodenum and distal
      colon. The neuroendocrine peptides that we investigated were: secretin, gastric
      inhibitory polypeptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin,
      vasoactive intestinal polypeptide (VIP), substance P, neurotensin, neuropeptide Y
      (NPY) and galanin. In the antrum, gastrin, somatostatin, VIP, substance P and NPY
      concentrations were significantly lower in obese diabetic mice than in the lean
      controls. There was no statistical difference between the obese mice and lean
      controls for neurotensin and galanin content. In the duodenum, the concentration
      of substance P was lower in the obese diabetic mice than in lean mice. There was
      no statistical difference between obese diabetic mice and lean controls regarding
      the concentration of secretin, GIP, motilin, gastrin, somatostatin, VIP,
      neurotensin, NPY or galanin. In the colon, the levels of PYY, somatostatin, VIP,
      substance P, NPY and galanin were significantly lower in the obese diabetic mice
      than the lean controls. The concentration of neurotensin in the obese mice did
      not differ from that in the lean controls. The present study showed that the
      neuroendocrine system is disturbed in an animal model of human type 2 diabetes
      and that this disturbance differs from that observed in other animal models of
      human type 1 diabetes. The present findings may have some implications for the
      gastrointestinal dysfunction observed in patients with type 2 diabetes.

PMID- 9934818
TI  - Rapid screening test evaluation for microalbuminuria in diabetes mellitus.
AB  - Microalbuminuria predicts clinical nephropathy and cardiovascular disease in
      diabetes mellitus. This study was undertaken to evaluate a screening
      microalbuminuria test with the Micral test II dipstick in a general practice
      setting and compare whether, if three urine samples are tested, any advantage is
      offered over a testing single sample. Two hundred and eighty diabetic patients
      attending a primary health care centre were studied. The first morning urine
      albumin concentration was determined by dipstick over 3 consecutive days. We
      studied two valuation methods: Method 1. Three-sample method: the test was
      considered positive if albumin was equal to or above 20 mg/l in at least two of
      three tests; Method 2. Single-sample method: we selected the third test, i.e. the
      most recent urine sample; if albumin was equal to or above 20 mg/l it was
      considered positive. The gold standard was the albumin excretion rate measured by
      a nephelometric method in a 24-h urine collection. Sensitivity, specificity,
      predictive values and Kappa coefficient were calculated. The diagnostic
      performance was assessed by a receiver operating characteristic curve.
      Microalbuminuria was defined for different thresholds of albumin excretion rate,
      15, 20, 25 and 30 microg/min: their frequency was 38, 29, 23 and 18%,
      respectively. For method 1, the sensitivity of Micral test II oscillated between
      70-94% and the specificity between 93-83%. For method 2, the sensitivity
      oscillated between 64-86%, and the specificity between 88-80%. Both methods had a
      high diagnostic performance. The Kappa coefficient was 84 and 60% for method 1
      and 2, respectively. The Micral test II is a rapid, valid and reliable method for
      microalbuminuria screening in diabetic patients. It constitutes an important tool
      for diabetic surveillance in general practice. Although the use of three samples
      provides better results, the use of a single sample produces acceptable results
      at a low cost.

PMID- 9934819
TI  - The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose
      uptake in the human forearm.
AB  - Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed
      to be of major importance for insulin-mediated glucose uptake. The aim of this
      study was to investigate the relative importance of blood flow and glucose
      extraction as determinants of insulin-mediated glucose uptake in the human
      forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were
      evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in
      nine healthy subjects. FBF was measured by venous occlusion plethysmography.
      Forearm glucose uptake increased sevenfold during the hyperinsulinaemia
      (P<0.001). Forearm glucose extraction showed a minor increase during the first 10
      min of hyperinsulinaemia, but the most marked increase took place between 10 and
      20 min (+170%). Thereafter, only a minor further increase was seen. During the
      first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased
      steadily to a plateau reached after 60 min (+50%, P<0.001). A close relationship
      between whole body glucose uptake and FBF was seen at the end of the clamp (r =
      0.75, P<0.02), but at this time the relationship between whole body glucose
      uptake and forearm glucose extraction was not significant. The modest increase in
      O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF
      during the early phase of the clamp. In conclusion, the early course of insulin
      mediated glucose uptake in the human forearm was mainly due to an increase in
      glucose extraction. However, with time the insulin-mediated increase in blood
      flow increased in importance and after 100 min of hyperinsulinaemia FBF was the
      major determinant of glucose uptake.

PMID- 9934820
TI  - Patient education and diabetes research: a failure! Going beyond the empirical
      approaches.
AB  - A literature review of 37 papers cited by MEDLINE between 1986 and April 1996
      under the terms "diabetes", "patient education" and "randomized" was carried out.
      The articles were analysed on the basis of a check list (Educational Procedure
      Check List), which contains 27 items grouped into 8 areas: study objectives,
      educational objectives, population, educational strategy, content, evaluation,
      outcome, final results. The results of our study show that authors do not
      describe the educational interventions that they have used; thus, we suggest that
      editors request randomized trial studies containing information on identification
      of patients' needs, elaboration of learning objectives, and planning and running
      of the program and the evaluation system used.

PMID- 9934821
TI  - Effects of the carbonic anhydrase inhibitor acetazolamide on splanchnic blood
      flow in anaesthetized rats.
AB  - The aim of the present study was to evaluate whether inhibition of the enzyme
      carbonic anhydrase with acetazolamide interfered with pancreatic islet and whole
      splanchnic blood perfusion in rats. Carbonic anhydrase is present both in the
      endocrine cells and, in particular, the endothelium of the pancreatic islet.
      Thiobutabarbital-anaesthetized, male Sprague-Dawley rats were used in all
      experiments, and acetazolamide (50 mg/kg body weight) was given to untreated
      control rats or rats pretreated with glucose, i.e. to normoglycaemic and
      hyperglycaemic animals. No acetazolamide-induced effects on blood glucose or
      serum insulin concentrations, mean arterial blood pressure, whole pancreatic or
      islet blood flow were seen in any of the animals. There were no effects on
      duodenal or colonic blood flow recorded in the control rats, whereas an increase
      in duodenal blood flow (P<0.02) was observed in the hyperglycaemic animals. A
      tendency to an increase was seen in colonic blood flow in hyperglycaemic animals,
      although this was not statistically significant (P = 0.069). Inhibition of
      carbonic anhydrase seems to induce only minor effects on pancreatic blood flow,
      while duodenal blood flow is slightly enhanced in hyperglycaemic animals.

PMID- 9934822
TI  - Bioelectrical characteristics of type 1 and type 2 diabetic subjects with
      reference to body water compartments.
AB  - Since bioelectrical characteristics correspond well to body water compartments,
      this study investigated bioelectrical differences between type 1 and type 2
      diabetic subjects that could reflect differences in body water compartments. We
      investigated cross-sectionally 612 adult subjects, classified into 10 groups
      according to sex and disease (control, obese normal glucose tolerant, non-obese
      type 2 diabetes, obese type 2 diabetes, type 1 diabetes). Resistance (R),
      reactance (Xc) and phase angle (PA) were measured (800 microA - 50 kHz
      alternating current). The bioelectrical vector was obtained by plotting R and Xc
      normalized for height (ht), it is easily identified on the basis of the length
      (inversely related to the total body water, likewise R) and direction, given by
      the PA (inversely related to the extra-/intra-cellular water - ECW/ICW -).
      Results show that disease and sex had a significant (ANOVA: P<0.0001 for both F
      disease and F sex) and independent effect on both R/ht and Xc/ht; no difference
      was found between type 2 and type 1 diabetic groups. A bioelectrical vector with
      a lower PA characterized both type 2 and type 1 diabetic groups. An independent
      positive correlation between fasting plasma glucose and R/ht and a negative
      correlation between fasting plasma glucose and PA were observed. These findings
      suggest a non-different body water content and distribution between type 2 and
      type 1 diabetic subjects; the bioelectrical vector indicates a higher ECW/ICW in
      type 2 and type 1 diabetic compared to nondiabetic subjects.

PMID- 9934823
TI  - Ernst-Friedrich-Pfeiffer-Memorial lecture. Hypoglycaemia associated syndrome.

PMID- 9934824
TI  - Role of shear stress and immune responses in liver regeneration after a partial
      hepatectomy.
AB  - This report reviews studies addressing the new concepts in liver regeneration
      after a partial hepatectomy (PHx). The review begins with an overview of the
      immunologic mechanisms of liver regeneration after PHx, especially regarding
      Kupffer cells and extrathymic T cells of the regenerative liver in the cell
      mediated immunity, based on major histocompatibility complex I and II antigens.
      Attention is then devoted to "on and off" studies in liver regeneration after
      PHx, by hypothesizing the shear stress based on the fact that the portal flow
      against hepatocytes or sinusoidal endothelial cells triggers their regeneration
      after a partial hepatectomy and controls the volume of the regenerating liver by
      the stimulating the cell surface modulator (CSM) of hepatocytes and sinusoidal
      endothelial cells (SEC). We propose that the acute elevation of shear stress
      after PHx influences the adhesion between SEC and intrahepatic leukocytes. These
      concepts are expected to positively contribute to the future research on liver
      regeneration after PHx.

PMID- 9934825
TI  - Tumor necrosis factor-alpha production after esophageal cancer surgery:
      differences in the response to lipopolysaccharide stimulation among whole blood,
      pleural effusion cells, and bronchoalveolar lavage fluid cells.
AB  - The body's defense mechanism in response to stress may appear to be the sum of
      activation and suppression. We investigated chronological changes in tumor
      necrosis factor-alpha (TNF-alpha) production by local effusion cells and whole
      blood of esophageal cancer patients who had undergone radical resection. Whole
      blood, pleural effusion cells, and bronchoalveolar lavage fluid (BALF) cells were
      obtained from the 20 patients. Whole blood was stimulated with Escherichia coli
      (1 microg/ml), Staphylococcus aureus (10 microg/ml), and lipopolysaccharide (LPS)
      (1 microg/ml), and pleural effusion cells and BALF cells were stimulated with
      LPS; 24-H incubation and TNF-alpha concentration in supernate was measured by
      enzyme-linked immunosorbent assay (ELISA). Within 3 h after starting the
      operation, TNF-alpha production in whole blood was significantly (P < 0.05)
      decreased compared with preoperative value by each stimulation, and this
      suppression persisted up to day 3. These reductions in postoperative TNF-alpha
      production correlated with intraoperative hemorrhage. On the other hand, the LPS
      induced release of TNF-alpha into pleural effusion cells and BALF cells were
      markedly increased during the study period. These results indicate that large
      quantities of cytokines are produced by a second attack, such as infection, in
      areas where immunocytes accumulate. We believe that the body reacts to surgical
      stress in a variety of ways. Circulating blood and immunocytes that accumulate in
      damaged organs are thought to react very differently to stress.

PMID- 9934826
TI  - The prognostic significance of lymph node metastasis and intrapancreatic
      perineural invasion in pancreatic cancer after curative resection.
AB  - To investigate the prognostic factors of pancreatic cancer, a retrospective
      analysis of 193 patients who underwent curative resection was conducted. Of the
      193 patients, 38 (20%) survived for more than 5 years, the 5-year survival rates
      for stages I, II, II, and IV disease being 41%, 17%, 11%, and 6%, respectively.
      According to a multivariate analysis, lymph node metastasis, intrapancreatic
      perineural invasion, and portal vein invasion were significant prognostic
      factors. Subsequently, a subgroup analysis concerning nodal metastasis and
      intrapancreatic perineural invasion was performed in 126 patients with records of
      these histological findings. In the group of patients without nodal metastasis,
      the 5-year survival rate for those without perineural invasion was 75%, whereas
      that for those with perineural invasion was 29%, the difference in survival of
      these subgroups being significant (P < 0.02). In the group of patients with nodal
      metastasis, the 5-year survival rate for those without perineural invasion was
      17%, while that for those with perineural invasion was 10%. The most favorable 5
      year survival of 89% was observed in the subgroup of patients with stage I
      disease without perineural invasion. Thus, pancreatic adenocarcinoma categorized
      by the combination of these independent types of biological behavior showed 5
      year survival rates ranging from very high to low, indicating that these two
      factors play an important role in the prognosis of this disease.

PMID- 9934827
TI  - Protective procedures following splenic rupture.
AB  - The aim of the present study was to improve spleen-preserving procedures in
      patients undergoing laparotomy following abdominal trauma. Of a total 288
      patients who underwent laparotomy for abdominal trauma in the Fourth General
      Surgical Department of Hardarpasa Teaching Hospital between 1989 and 1996, 94
      patients with splenic injuries were retrospectively analyzed. The mean age of
      these 94 patients, 69% whom were male, was 28.9 +/- 3.5 years. Traffic accidents
      were found to be the major cause of splenic injuries (71.3%) and diagnostic
      peritoneal lavage was frequently used as a diagnostic tool (58.8%). Grades IV and
      V splenic injuries were seen in 71 patients (75.4%), all of whom required
      splenectomy. Omentoplasty with partial splenectomy or omentoplasty with
      splenorrhaphy successfully controlled hemorrhage from the spleen in 22 patients
      (23.4%). The complication rate was calculated at 18.06% in this study, but no
      deaths occurred as a direct result of splenic injury. In conclusion,
      omentoplasty, partial splenectomy, and splenorrhaphy are safe and successful
      methods of controlling bleeding from a damaged spleen of grade III in patients
      without multiple injuries.

PMID- 9934828
TI  - The effects of cardiopulmonary bypass on postoperative oxygen metabolism.
AB  - The relationships between oxygen delivery (DO2), oxygen consumption (VO2), and
      the extraction rate (ER = VO2/DO2 x 100) in patients undergoing cardiopulmonary
      bypass (CPB) may differ from the normal physiologic state due to the oxygen debt
      acquired during CPB. Blood gas analysis and hemodynamic parameters were
      repeatedly measured for the determination of DO2 and VO2 in 40 patients
      undergoing CPB, every 8 h during the first 48 h postoperatively. As a control, 20
      patients who had suffered acute myocardial infarction (AMI) were also studied
      using the same protocol. In the CPB group, a regression analysis showed that VO2
      was significantly dependent on DO2, even within the physiologic range of DO2
      (>500 ml/min per m2); VO2 = 121.4 + 0.0844 x DO2 (r = 0.254, P = 0.023).
      Conversely, in the AMI group, no such supply-dependent consumption was observed
      within the same range of DO2. At an ER of 30%, which is the optimal value in
      general, the DO2 of the CPB group was 575 ml/min per m2 and that of the AMI group
      was 493 ml/min per m2. All these results suggest that patients undergoing CPB
      need a much higher oxygen supply to recover from the oxygen debt acquired during
      open heart surgery.

PMID- 9934829
TI  - The importance of total parenteral nutrition-associated tissue zinc distribution
      in wound healing.
AB  - It is well known that zinc (Zn), an essential trace element, plays a role in
      wound healing. Although the importance of Zn supplementation in total parenteral
      nutrition (TPN) has been recognized, the difference in tissue Zn distribution
      induced by TPN and whether this difference influences local wound healing remains
      uncertain. Thus, we conducted a study using 30 Sprague-Dawley rats to investigate
      the influence of TPN-induced changes in tissue Zn distribution on wound healing
      at sites of intestinal anastomosis, muscle, and skin sutures. In the ordinary
      diet group, no significant differences were observed between subgroups with and
      without supplemental Zn in tissue Zn distribution or in the healing of
      intestinal, muscular, and cutaneous wounds. In the subgroup given a low-protein
      diet without supplemental Zn, a gross change in tissue Zn distribution was noted
      to occur with a concomitant marked decrease in Zn concentration and the tensile
      strength of wounded skin. These results indicate an association between wound
      healing and Zn concentration in the respective tissues in TPN-induced Zn
      deficiency with alternations in tissue Zn distribution. They also provide
      evidence of the local action of Zn in wound healing.

PMID- 9934830
TI  - Prostaglandin synthetase inhibition reduces peritonitis-induced early liver
      oxidant stress.
AB  - This study was undertaken to determine whether or not the prostanoid metabolism
      contributes to peritonitis-induced early liver oxidant stress. Lipid peroxidation
      products, malondialdehyde (MDA) and conjugated dienes (CD), were used to monitor
      oxidant stress. The rats were given a 5-cc intraperitoneal (i.p.) injection of
      25% rat feces suspension and then received either i.p. saline (peritonitis group,
      n = 11), vitamin E (n = 6), or diclofenac (n = 6). The liver and plasma MDA and
      CD levels were measured after 3 h. The plasma and liver MDA and CD levels were
      significantly higher in the peritonitis group than in the control (n = 9).
      Prostaglandin synthetase inhibitor (diclofenac) kept the liver and plasma MDA and
      CD at control levels. Antioxidant alpha tacopherol (vitamin E) was thus found not
      to be effective in reducing these increased MDA and CD levels. Peritonitis
      induced early oxidant stress in the liver seems to be mediated by the oxidant
      independent activation of the cyclooxygenase pathway.

PMID- 9934831
TI  - Hypertonic saline prevents early bacterial translocation in hemorrhagic shock.
AB  - The most appropriate solution for volume replacement in hemorrhagic shock is
      controversial; however, hypertonic saline (HTS) solutions have recently gained
      widespread acceptance. In this study, various solutions were used to resuscitate
      rats in hemorrhagic shock, and their impact on the extent of bacterial
      translocation was investigated. Rats were bled to a mean arterial blood pressure
      of about 35 mmHg which was maintained for 30 min. They were then randomized into
      six groups. Blood pressure was found to be regulated by blood + lactated Ringer's
      solution (LR) and HTS + LR, but no significant improvement was observed in the
      control and LR groups. Groups II (7.5% HTS + 60 ml/kg LR) and IV (60 ml/kg LR +
      autologous blood) had a significantly better result than groups I (7.5% HTS), III
      (60 ml/kg LR), and IV (P < 0.05), among which no statistically different results
      were seen (P > 0.05). While no organisms were isolated from the mesenteric lymph
      nodes in the sham group, the rates of positive culture were 12.5%, 12.5%, 50%,
      62.5%, and 62.5% in groups I, II, III, and the control group, respectively.
      Escherichia coli was the most commonly isolated organism. HTS + LR was
      demonstrated to be effective for decreasing the rate of early bacterial
      translocation to mesenteric lymph nodes and also for restoring the mean arterial
      pressure.

PMID- 9934832
TI  - The prevention of postoperative intraperitoneal adhesions by tranilast: N-(3',4'
      dimethoxycinnamoyl)anthranilic acid.
AB  - The development of postoperative intraperitoneal adhesions continues to be a
      major concern for surgeons. The purpose of this study was to establish a
      postoperative adhesion model in rats, and to assess the effectiveness of
      tranilast (N-(3',4'-dimethoxycinnamoyl)anthranilic acid) in preventing
      postoperative adhesion formation. The adhesion model was established in 12 male
      Donryu rats. This involved two essential factors, drying and bleeding. Another 22
      male Donryu rats were used to study the prevention of intraperitoneal adhesions.
      Tranilast was administered orally pre- and postoperatively. Adhesion strength was
      evaluated by grading, and basic fibroblast growth factor (bFGF) and transforming
      growth factor-beta-1 (TGF-beta1) concentration were measured. Postoperative
      intraperitoneal adhesions were seen in all rats, but the adhesions in the
      tranilast group were significantly less severe than those in the control group.
      Serum bFGF and TGF-beta1 levels in the tranilast group were lower at the time of
      surgery than those in the control group, and bFGF levels were lower at the
      endpoint of this study in the tranilast group than in the control group. The TGF
      beta1 levels at the end-point did not differ between the two groups. These
      findings demonstrated that tranilast significantly reduced postoperative
      intraperitoneal adhesion formation.

PMID- 9934833
TI  - Correlation of the therapeutic effect of activated tumor-draining lymph node
      cells with specific interferon-gamma production in vitro.
AB  - It has been established that lymphocytes obtained from tumor-draining lymph nodes
      (DLN) are sensitized to the tumor antigen in vivo. Moreover, after being
      activated in vitro, these cells can be utilized for adoptive immunotherapy. In
      the present study, DLN cells, obtained from C57BL/6 mice with fibrosarcoma (MC
      1), were activated and expanded with anti-CD3 monoclonal antibody followed by
      culture with recombinant interleukin-2 (rIL-2). These CD4- CD8+ CD25+ CD44+ T
      cells showed specific antitumor efficacy to the pulmonary micrometastases of an
      autologous tumor, against which lymphokine-activated killer cells were
      ineffective; however, they did not show cytolytic activity in vitro. The
      supernatant, obtained by coculturing the activated DLN cells with MC-1 cells,
      exhibited the specific production of interferon-gamma (IFN-gamma) which was
      enhanced by rIL-2. The therapeutic effect of the activated DLN cells correlated
      with the specific IFN-gamma production better than with the cytolytic activity.

PMID- 9934834
TI  - Familial hyperparathyroidism: report of a case.
AB  - We report herein a case of familial primary hyperparathyroidism diagnosed in a 23
      year-old woman who presented with hypercalcemia and urolithiasis. The parathyroid
      gland was removed, and pathological examination revealed chief cell adenoma. The
      proband's younger sister had undergone surgery for parathyroid adenoma at the age
      of 19, and her aunt had a history of urolithiasis with a high level of serum
      parathyroid hormone. We have not yet found evidence of any other endocrine
      disorders suggesting multiple endocrine neoplasia (MEN) type 1 in this pedigree.

PMID- 9934835
TI  - Combined right hepatic and retrohepatic caval resection with reconstruction using
      a polytetrafluoroethylene graft for primary leiomyosarcoma of the liver: report
      of case.
AB  - We present herein the case of a 53-year-old woman who underwent successful
      surgical treatment for a leiomyosarcoma of the liver that originated from the
      posterior hepatic segment and involved the retrohepatic inferior vena cava (IVC).
      A computed tomographic scan and magnetic resonance imaging demonstrated a large
      tumor, with rich vascularity, in the liver. The IVC was found to be occluded on
      these scans, which was confirmed by venacavography. The patient underwent a
      combined right hepatic and caval resection with reconstruction using an expanded
      polytetrafluoroethylene graft. The tumor consisted of spindle-shaped cells with
      cigar-shaped nuclei. It also had a moderate degree of cellularity and ten mitotic
      figures per ten high-power fields. Immunohistologically, desmin and alpha-smooth
      muscle actin were stained positive in the tumor cells, implying that the tumor
      was derived from smooth muscle cells. The patient is alive and well 15 months
      after her operation.

PMID- 9934836
TI  - Port site recurrence of unexpected gallbladder carcinoma after a laparoscopic
      cholecystectomy: report of a case.
AB  - Unexpected gallbladder carcinoma was identified in a 71-year-old woman after she
      underwent a laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis. A
      subsequent laparotomy for a resection of the liver bed and a dissection of the
      lymph nodes around the hepatoduodenal ligament was done. Two and a half years
      later, the patient developed subcutaneous metastasis at the epigastric trocar
      site through which the gallbladder was removed. A third operation was thus
      performed, revealing no evidence of peritoneal dissemination, liver metastasis,
      or lymph node metastasis, and the abdominal wall mass was resected. The
      histological findings confirmed the diagnosis of metastatic carcinoma of the
      gallbladder. We recommend that when planning LC, the possibility of malignancy
      should thus be kept in mind. However, if there is any sign which does not
      completely exclude malignancy, such as a contracture or wall thickness of the
      gallbladder, LC should be performed by the abdominal wall lifting method and
      using a protective bag for the removal of the gallbladder.

PMID- 9934837
TI  - Splenic artery aneurysm associated with systemic lupus erythematosus: report of a
      case.
AB  - We herein report on a 64-year-old Japanese female patient who presented with a
      splenic artery aneurysm (SAA) associated with systemic lupus erythematosus (SLE).
      The saccular aneurysm, which measured 3 cm in diameter, was located in the
      proximal third of the splenic artery from the pancreas with a portosystemic
      shunt. A double ligation of the splenic artery (the distal and proximal sides of
      the aneurysm) was performed without a splenectomy. The postoperative course
      showed acute pancreatitis without either splenic infarction or portal thrombus.
      To our knowledge, the closed association of SLE with an aneurysmal dilatation of
      the splenic artery has not been previously reported. Both the pathogenesis and
      the management of SAA associated with SLE are discussed following the
      presentation of this case. This is the first reported case of SAA associated with
      SLE.

PMID- 9934838
TI  - Coexisting extraadrenal pheochromocytoma and von Meyenberg complexes: report of a
      case.
AB  - We herein report on a 62-year-old man who developed extraadrenal pheochromocytoma
      and von Meyenberg complexes of the liver (bile duct microhamartoma). The patient
      identified preoperatively as having a paraaortic mass which was subsequently
      diagnosed to be a pheochromocytoma. During the operation, small multiple nodules
      were unexpectedly recognized in the liver. Some of the liver nodules were
      resected by a wedge biopsy, and then were pathologically identified to be von
      Meyenberg complexes. This may be the first reported case of the coexistence of
      pheochromocytoma and von Meyenberg complexes. It is therefore necessary for
      surgeons to be aware of von Meyenberg complexes in the differential diagnosis of
      multiple liver metastases in malignant disease.

PMID- 9934839
TI  - Combined catheter embolization and femorofemoral bypass for pseudoaneurysm of the
      right external iliac artery: report of a case.
AB  - Performing direct surgery for postoperative hemorrhage caused by intraperitoneal
      arterial injury is very difficult. We report herein the case of a 52-year-old
      woman who developed sudden right lower abdominal pain after numerous laparotomies
      and radiotherapy for advanced uterine cancer. A diagnosis of pseudoaneurysm of
      the right external iliac artery was made, and an emergency catheter embolization
      and femorofemoral bypass was successfully performed under local anesthesia. The
      patient was able to walk the next day. To the best of our knowledge, this is the
      first report of such a combined procedure in the literature.

PMID- 9934840
TI  - Omentum autotransplantation in thromboangiitis obliterans: report of three cases.
AB  - Thromboangiitis obliterans (TAO), also known as Buerger's disease, is an
      important cause in India of chronic arterial occlusion of the limbs. The current
      modalities of therapy do not provide adequate relief to a large number of these
      patients. An omentum autotransplantation to the lower limbs was performed in
      three patients as a limb salvage procedure. The initial results with up to a year
      of follow-up are so far encouraging.

PMID- 9934841
TI  - Serum levels of NCC-ST-439 in Dukes' C colorectal cancer patients: a preliminary
      report.
AB  - The serum levels of NCC-ST-439, a monoclonal antibody raised against a human
      gastric cancer xenograft (ST-439), were determined in 28 patients who had
      undergone a curative resection of Dukes' C colorectal carcinoma. The preoperative
      mean levels of NCC-ST-439 were 14.4 U/ml (range 1.0-280.0) and positive (>7.0
      U/ml for women under the age of 49, >4.5 U/ml for women over the age of 50, and
      men at any age) in 6 patients. Recurrence of the disease after a curative
      resection was encountered in 7 patients (serum NCC-ST-439 was positive in 5 and
      negative in 2 patients). The positive serum NCC-ST-439 was associated with a
      significantly poorer disease-free survival time (P < 0.0001). In patients who had
      undergone a curative resection of Dukes' C colorectal cancer, the sensitivity of
      NCC-ST-439 in the sera for recurrent disease was 71.4% and specificity was 95.2%.
      The results of a preliminary study suggested NCC-ST-439 to be a novel marker for
      predicting recurrence after a curative resection of Dukes' C colorectal
      carcinoma.

PMID- 9934842
TI  - Coloanal anastomosis using a circular stapling device following perineal
      rectosigmoidectomy for rectal prolapse.
AB  - Perineal rectosigmoidectomy with a hand-sewn anastomosis is thought to be the
      most appropriate procedure for elderly patients deemed unfit to tolerate a major
      abdominal operation. However, the use of a circular stapling device to perform
      the coloanal anastomosis following rectosigmoidectomy shortens the operative time
      and provides a more secure anastomosis than the traditional hand-sewn technique.

PMID- 9934843
TI  - The light at the end of the tunnel for chemical-specific biomarkers: daylight or
      headlight?

PMID- 9934844
TI  - A malignant transformation of human cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin
      exhibits altered expressions of growth regulatory factors.
AB  - The neoplastic transformation of human cells in culture with exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) has recently been reported. In this study,
      expressions of growth regulatory factors were analyzed to examine their possible
      roles in TCDD-induced malignant transformation of human cells. Reverse
      transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis were
      performed to detect altered expressions of genes associated with dioxin
      responses. The RT-PCR analysis showed that expressions of the growth regulatory
      factors, such as transforming growth factor-beta1 (TGF-beta1), plasminogen
      activator inhibitor-2 (PAI-2) and tumor necrosis factor-alpha (TNF-alpha), were
      significantly changed in the transformed cells as compared with the parental
      cells. Whereas parental cells showed a dose-dependent increase of PAI-2 mRNA
      levels following TCDD exposure, the transformed cells did not show any
      significant induction. In addition, constitutive levels of PAI-2 mRNA were 25
      times lower in the transformed cells than in the parental cells. The mRNA
      stability assay suggests that downregulation of PAI-2 mRNA in the transformed
      cells may be associated with the posttranscriptional control. Expression of TGF
      beta1 mRNA in the transformed cells was also four times lower than the parental
      cells. However, levels of TNF-alpha mRNA in the transformed cells were increased
      3-fold. These results suggest that dysregulation of growth regulatory factors may
      be involved in TCDD-induced cellular transformation. Whereas plenty of studies
      demonstrated a number of immediate toxic effects by TCDD, this study revealed an
      initial evidence that altered expression of growth regulatory genes, such as PAI
      2, TGF-beta1 or TNF-alpha, are some of the genetic events fixed in the genome
      following the successive cell divisions of TCDD-damaged cells. It is suggested
      that these changes may be associated with TCDD-induced malignant transformation
      of human cells.

PMID- 9934845
TI  - UV-enhanced reactivation of a UV-damaged reporter gene suggests transcription
      coupled repair is UV-inducible in human cells.
AB  - The genetic disorders xeroderma pigmentosum (XP) and Cockayne syndrome (CS)
      exhibit deficiencies in the repair of UV-induced DNA damage. CS fibroblasts
      retain proficient nucleotide excision repair (NER) of inactive (or bulk) DNA, but
      are deficient in the transcription-coupled repair (TCR) of active genes. In
      contrast, XP complementation group C (XP-C) fibroblasts retain proficient TCR,
      but are deficient in bulk DNA repair. The remaining NER-deficient XP groups
      exhibit deficiencies in both repair pathways. Ad5HCMVsp1lacZ is a recombinant
      adenovirus vector that is unable to replicate in human fibroblasts, but can
      efficiently infect and express the beta-galactosidase reporter gene in these
      cells. We have examined the host cell reactivation (HCR) of beta-galactosidase
      activity for UV-irradiated Ad5HCMVsp1lacZ in non-irradiated and UV-irradiated
      normal, XP-B, XP-C, XP-D, XP-F, XP-G, CS-A and CS-B fibroblasts. HCR of beta
      galactosidase activity for UV-irradiated Ad5HCMVsp1lacZ was reduced in non
      irradiated cells from each of the repair-deficient groups examined (including XP
      C) relative to that in non-irradiated normal cells. Prior irradiation of cells
      with low UV fluences resulted in an enhancement of HCR for normal and XP-C
      strains, but not for the remaining XP and CS strains. HCR of the UV-damaged
      reporter gene in UV-irradiated XP and CS strains was similar to measurements of
      TCR reported previously for these cells. These results suggest that UV treatment
      results in an induced repair of UV-damaged DNA in the transcribed strand of an
      active gene in XP-C and normal cells through an enhancement of TCR or a mechanism
      which involves the TCR pathway.

PMID- 9934846
TI  - Kupffer cell oxidant production is central to the mechanism of peroxisome
      proliferators.
AB  - Increased cell proliferation most likely plays a key role in peroxisome
      proliferator-induced liver cancer. Recently, Kupffer cells were shown to be
      responsible for Wy-14,643-induced cell proliferation. However, the mechanism by
      which peroxisome proliferators activate Kupffer cells is unknown. Since gut
      derived endotoxin is a known activator of Kupffer cells, the hypothesis that it
      is involved was evaluated. Increased cell proliferation and peroxisome induction
      were unaffected by gut sterilization. Moreover, endotoxin was not detectable in
      portal blood following treatment with Wy-14,643. Therefore, it is concluded that
      gut-derived endotoxin is not responsible for Kupffer cell activation. To test the
      hypothesis that Kupffer cells are activated by Wy-14,643 directly, Kupffer cell
      superoxide production was measured following treatment in vitro. Wy-14,643
      increased superoxide production in a dose-dependent manner (0.1 and 50 microM)
      with half-maximal stimulation at 2.5 microM. Diethylhexylphthalate (DEHP) and
      ethylhexanol did not increase superoxide production even at doses 50 times higher
      than Wy-14,643; however, monoethylhexylphthalate (MEHP) activated superoxide
      production as effectively as Wy-14,643 with half-maximal stimulation at 5 microM.
      Treatment with Wy-14,643 for 21 days caused a 2-fold increase in Kupffer cell
      superoxide production while DEHP did not. Pretreatment of Kupffer cells with
      staurosporine (0.01-10 pM) completely blocked generation of superoxide
      demonstrating that protein kinase C is required. Moreover, Wy-14,643 increased
      Kupffer cell protein kinase C activity 3-fold. Pretreatment of Kupffer cells with
      the amino acid glycine (0.01-3 mM), which blunts calcium signaling, inhibited Wy
      14,643-stimulated superoxide production and increased protein kinase C activity
      completely. These data are consistent with the hypothesis that potent peroxisome
      proliferators (Wy-14,643 and MEHP) directly activate Kupffer cell production of
      oxidants via mechanisms involving protein kinase C. Further, peroxisome
      proliferator treatments that sustain elevated rates of cell proliferation (e.g.
      Wy-14,643) activate Kupffer cell superoxide production following long-term
      dietary treatment supporting the hypothesis that Kupffer cell-derived oxidants
      are involved in peroxisome proliferator-induced neoplasia.

PMID- 9934847
TI  - 238Pu alpha-particle-induced C3H10T1/2 transformants are less tumorigenic than
      the X-ray-induced equivalent.
AB  - Transformation is a complex multistage process in vitro by which benign cells
      gradually acquire characteristics of tumour cells. Transformed C3H10T1/2 cells
      appear in vitro as multilayers of cells termed foci. A variety of transformed
      phenotypes are observed in vitro and in this study samples of these phenotypes
      were developed as cell lines and assessed for their ability to induce tumours in
      C3H mice. It was found that, while a high proportion of X-ray-induced
      transformants were tumorigenic, most of the alpha-particle-induced transformants
      were non-tumorigenic. Although tumours produced by the X-ray-induced
      transformants appeared earlier, they grew at similar rates to the alpha-particle
      induced equivalent. Foci were classified as fully or partially tumorigenic
      depending on whether the foci produced at least one tumour in the mice injected
      (partially tumorigenic) or produced tumours in all mice injected (fully
      tumorigenic). It was found that tumours from the partially tumorigenic foci grew
      slower or appeared later than those of the fully tumorigenic foci. It is
      hypothesized that the apparent low tumorigenicity of positively transformed alpha
      particle-induced foci is due to an increase in genomic instability of progeny
      focus cells compared with X-ray-induced foci leading to a larger non-viable
      population of cells in the alpha-particle-induced foci.

PMID- 9934849
TI  - Chemoprevention of intestinal adenomas in the ApcMin mouse by piroxicam:
      kinetics, strain effects and resistance to chemosuppression.
AB  - Previous cancer chemoprevention studies have demonstrated that NSAIDs can be
      effective in suppressing the development of intestinal tumors. To further explore
      this issue, we performed cross-over chemoprevention studies using the drug
      piroxicam in the ApcMin mouse to evaluate the kinetics of NSAID-mediated tumor
      regression, the effects of genetic background and the incidence of resistance to
      chemoprevention. Starting at the time of weaning, C57BI/ 6J-ApcMin mice were fed
      either the control diet (AIN-93G) or AIN-93G plus 200 p.p.m. piroxicam. Tumor
      multiplicity was significantly reduced in ApcMin mice that were fed 200 p.p.m.
      piroxicam until 100 or 200 days of age (94.4 and 95.7% reduction in tumor number,
      respectively; P < 0.001 versus AIN-93G controls). When the administration of
      piroxicam was delayed until 100 days of age and the mice were killed at 200 days
      of age, tumor multiplicity was reduced by 96.2% (P < 0.001 versus controls).
      Alternatively, when the administration of piroxicam was suspended at 100 days of
      age and the mice were killed at 200 days of age, tumor multiplicity was reduced
      by 68.0% (P < 0.001 versus controls). Short-term drug treatment periods for
      ApcMin animals with established tumors revealed that the kinetics of piroxicam
      induced tumor regression were rapid: >90% reduction in tumor multiplicity was
      observed after 1 week of treatment with 200 p.p.m. piroxicam. The distribution of
      residual tumors in piroxicam-treated mice suggests that tumors of the duodenum
      and colon were relatively resistant to chemosuppression. Treatment of
      interspecific hybrid ApcMin mice with 200 p.p.m. piroxicam revealed that there
      was a strain-related effect on chemosuppression, suggesting the existence of
      genetic elements which modulate NSAID chemosensitivity. Finally, whole-genome
      allelic loss studies showed that there were few unique chromosomal deletions in
      the NSAID-resistant tumors from F1 mice, implying that loss-of-function mutations
      secondary to Apc inactivation are not likely to account for the observed
      difference in chemoresistance.

PMID- 9934848
TI  - Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by
      inducing hypertrophy and inhibiting apoptosis.
AB  - Phenobarbital (PB) is a non-genotoxic liver tumor promoter used extensively in
      initiation-promotion protocols. To determine the mode of PB action, double
      transgenic mice overexpressing both the c-myc and transforming growth factor
      (TGF)-alpha genes were treated with PB in the food for 10 weeks, from 3 weeks of
      age. After 3-4 weeks on PB a peak in liver mass was noted, which subsequently
      leveled off at a value approximately 30% above untreated animals. The mitotic
      index in mice given PB peaked at 1 week of treatment and was significantly
      elevated compared with untreated animals. No significant difference between
      treated and untreated animals was seen thereafter, although a trend of PB
      associated mitotic suppression was noticeable. The apoptotic index also showed a
      trend of suppression compared with untreated animals, significant after prolonged
      PB administration. Dysplastic hepatocytes were more prominent in PB-treated mice
      than untreated animals, particularly pericentrally. Removal of PB from the diet
      at 4 weeks of treatment led to a dramatic increase in apoptosis. This accompanied
      a drop in the liver mass to the level of untreated controls by 10 days.
      Throughout the study, PB-treated animals showed markedly lower levels of TGF
      beta1 ligand, coincident with an elevated level of the anti-apoptotic protein Bcl
      2. On withdrawal of PB, the levels of all these proteins rapidly changed to
      mirror those seen in untreated mice. In all treatment groups, no change in the
      levels of epidermal growth factor receptor, TGF-beta receptors I and II or Bcl
      xS/L were seen. We conclude from our data that PB stimulates liver growth in
      double transgenic c-myc/TGF-alpha mice by induction of liver hypertrophy and
      inhibition of apoptosis, brought about by both a decrease in signaling through
      the TGF-beta pathway and an increase in Bcl-2. The data support the hypothesis
      that PB promotes neoplastic development through a reduction in the incidence of
      cell death.

PMID- 9934850
TI  - Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine
      treated mice.
AB  - Glycyrrhizin (GL) is widely used in Japan as a therapeutic agent for chronic
      active liver diseases. However, its action on hepatocarcinogenesis remains to be
      elucidated. To clarify its effect, mice treated with diethylnitrosamine (NDEA)
      with or without GL were analyzed. Five-week-old male BALB/c mice were divided
      into two groups, GL (n=50) and C (n=47). Mice in the GL group intramuscularly
      received 2 mg of GL 3 days a week, and mice in the C group received the same
      volume of saline in the same way. After 2 weeks, the mice were treated with an
      i.p. injection of 75 mg/kg body wt of NDEA weekly for 3 weeks and 100 mg/kg body
      wt of NDEA weekly for the following 3 weeks. Thirty additional mice that did not
      receive NDEA treatment were divided into two groups, GC (n=15) and SC (n=15).
      They received GL or saline, respectively. Mice in the 4 groups were killed every
      5 weeks after the last injection of NDEA from 7 weeks to 32 weeks. Liver function
      tests such as AST and albumin were significantly improved in the GL group
      compared with the C group (P < 0.05, each). Although liver nodules appeared in
      the C group at 22 weeks, they were not observed until 32 weeks in the GL group.
      At 32 weeks, the mean number of liver tumors, composed of adenoma and
      hepatocellular carcinoma (HCC), in the GL group was 0.71, which was significantly
      decreased compared with 1.64 of the C group (P < 0.05). The mean number of HCC in
      the GL group was 0.29/liver, which was lower than 0.82/liver in the C group (P <
      0.05). The incidence rate of HCC at 32 weeks was 64% in the C group and 21% in
      the GL group (P < 0.05, C versus GL group). Our results suggest that GL treatment
      inhibits the occurrence of HCC.

PMID- 9934851
TI  - Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma
      xenografts: role of apoptosis.
AB  - Our previous studies indicate that cadmium in mice can inhibit the formation of
      chemically induced and spontaneously occurring tumors in the liver and lung.
      Cadmium is an effective anti-tumor agent when given at non-toxic doses and even
      when given well after tumor formation, implying a unique sensitivity in certain
      tumor cells. The present studies tested the ability of cadmium to inhibit growth
      and progression of transplanted human pulmonary tumor xenografts. Male athymic
      nude mice were inoculated with either H460 cells, originally derived from a non
      small cell pulmonary carcinoma, or DMS 114 cells, originally derived from a small
      cell lung carcinoma, under the left renal capsule. Starting 1 week later mice
      received 0, 125 or 250 p.p.m. cadmium in the drinking water, levels without
      effect on host animal growth or survival, and were observed over the next 4 weeks
      (H460 cells) or 100 days (DMS 114 cells). An additional experiment gave cadmium
      as an i.v. loading dose (20 micromol/kg) 4 days after renal inoculation with H460
      cells and 200 p.p.m. cadmium in the drinking water from 7 days onward, with an
      observation period of 28 days. Cadmium caused dose-related reductions in the
      growth of tumors resulting from the inoculation of either H460 or DMS 114 cells
      of up to 83%. Additionally, cadmium reduced the rate of tumor metastasis to the
      lung by up to 58%. Cadmium treatment had no effects on either Bcl-2 or Bax
      protein expression in tumor xenografts, indicating that apoptotic pathways
      probably do not contribute to this anti-neoplastic effect. These studies show
      cadmium can effectively reduce growth and progression of human lung carcinoma
      xenografts in a fashion that is probably independent of apoptosis.

PMID- 9934852
TI  - Effect of reduced body weight gain on the evaluation of chemopreventive agents in
      the methylnitrosourea-induced mammary cancer model.
AB  - These studies examined whether the small to moderate reductions in body weight
      gain (< or = 15%) affect mammary carcinogenesis. Beginning 1 week prior to
      methylnitrosourea (MNU) administration (experiment 1), rats received diets
      supplemented with 4-hydroxyphenylretinamide (4-HPR) (782 mg/kg of diet) and
      retinyl acetate (328 mg/kg of diet) or underwent food restrictions. Rats were
      administered an i.v. dose of MNU (50 mg/kg body wt) at 50 days of age. Although
      the final body weights were similarly depressed by 4-HPR (8%) and by retinyl
      acetate (11%) from rats fed ad libitum, the kinetics of inhibition were quite
      different. Whereas 4-HPR caused an acute decrease in body weight at the time it
      was administered, the effect of retinyl acetate was more chronic. At 110 days
      after the administration of MNU, the average number of mammary cancers per rat
      was 4.9 for rats fed ad libitum, 1.3 for rats fed 4-HPR, 3.1 when body weights
      were matched to 4-HPR-treated rats, 1.9 for retinyl acetate and 3.2 when body
      weights were matched to retinyl acetate. Experiment II was performed to determine
      the minimal degree of acute body weight gain reduction that would alter MNU
      induced mammary carcinogenesis. Body weight gain depressions of 3, 6, 9, 12 and
      15% were initiated at 43 days of age by dietary restrictions and MNU was
      administered at 50 days of age. At 120 days after MNU, the percentage decreases
      in mammary cancer multiplicity in the various groups were 14, 15, 41, 44 and 55%,
      respectively. These data demonstrate that moderate reductions (9-15%) in body
      weight gain, in particular when occurring during the initiation and early
      promotion stages can greatly affect cancer multiplicity.

PMID- 9934853
TI  - Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in
      human esophageal cancer in Linxian, China.
AB  - p16INK4a and p15INK4b genes, which encode two functionally related CDK
      inhibitors, recently emerged as candidate tumor suppressor genes since they were
      both localized to 9p21, which frequently undergoes hemizygous and homozygous
      deletion in a variety of tumor types. To determine the mode of inactivation of
      these two genes in human esophageal squamous cell carcinoma (ESCC), we performed
      multiple molecular analyses in 60 ESCC specimens from Linxian, China using DNA
      methylation assay, LOH analysis, deletion screening and SSCP-sequencing. We
      observed that p16INK4a inactivation was predominantly associated with aberrant
      methylation in the CpG island of its promoter region, whereas p15INK4b frequently
      had homozygous deletions. Compared with aberrant methylation, which occurred in
      17 of 34 cases, homozygous deletion of p16INK4a and LOH at its nearby D9S942
      microsatellite marker were observed at a much lower frequency (17%). Intragenic
      mutation in p16INK4a gene was rare. In contrast, homozygous deletion in p15INK4b
      and LOH at the nearby D9S171 marker were observed at frequencies of 35 and 47%,
      respectively, and the two events were significantly associated with each other.
      On the other hand, aberrant methylation of p15INK4b was relatively infrequent
      (6/34) and occurred concomitantly with p16INK4a methylation. Among the 60 cases,
      only four contained a continuous homozygous deletion spanning both p15INK4b and
      p16INK4a. Six cases were exclusively deleted at p16INK4a and 17 exclusively
      deleted at p15INK4b. LOH at D9S942 and D9S171 was also found to be mutually
      exclusive. Our results suggest that the alteration mode at 9p21 was not uniform,
      and the two genes were inactivated by distinct mechanisms. Altogether, 68% of the
      samples harbor at least one type of alteration in p16INK4a gene and 50% of the
      samples were altered in p15INK4b gene, indicating that they are the frequent
      inactivating targets during ESCC development.

PMID- 9934854
TI  - Molecular modeling of the major adduct of (+)-anti-B[a]PDE (N2-dG) in the eight
      conformations and the five DNA sequences most relevant to base substitution
      mutagenesis.
AB  - The potent mutagen/carcinogen 7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene [(+)-anti-B[a]PDE], which is the activated form of
      benzo[a]pyrene (B[a]P), is able to induce different kinds of mutations (G-->T, G-
      >A, etc.). One hypothesis for this is that different mutations are induced
      depending upon the conformation of its major adduct ([+ta]-B[a]P-N2-dG) when
      bypassed during DNA replication. Based on molecular modeling, there appear to be
      at least 16 potential conformations that the major adduct [+ta]-B[a]P-N2-dG can
      adopt in dsDNA. Regarding base substitution mutagenesis, eight conformations are
      most likely to be relevant. In two conformations the dG moiety of the adduct is
      base paired with its complementary dC and the B[a]P moiety is in the minor
      groove. In two others the dG moiety of the adduct is in the Hoogsteen orientation
      and the B[a]P moiety is in the major groove. There are four base displaced
      structures in which the B[a]P moiety of the adduct is stacked with the
      surrounding base pairs, two with dG in the major groove and two with dG in the
      minor groove. Using a simulated annealing protocol, these eight conformations
      were evaluated in five different DNA sequence contexts (5'-TGC-3', 5'-CGT-3', 5'
      AGA-3', 5'-CGG-3' and 5'-GGG-3'); the latter were chosen because they may be
      particularly revealing about mutagenic mechanism based on studies with [+ta]
      B[a]P-N2-dG and (+)-anti-B[a]PDE. For each conformation and each sequence
      context, 25 simulated annealing runs were conducted by systematically varying
      several parameters (such as the initial annealing temperature) based on a
      protocol established recently. The goal of this work was to exclude conformations
      that are clearly inferior. Three conformations are virtually always high in
      energy, including the two Hoogsteen oriented species and one of the base
      displaced species with dG in the major groove. Remarkably, the remaining five
      conformations are often quite close in energy and are deemed most likely to be
      relevant to mutagenesis (see accompanying paper).

PMID- 9934855
TI  - A hypothesis for what conformation of the major adduct of (+)-anti-B[a]PDE (N2
      dG) causes G-->T versus G-->A mutations based upon a correlation between
      mutagenesis and molecular modeling results.
AB  - Molecular modeling (simulated annealing) was used to study the conformations in
      dsDNA of [+ta]-B[a]P-N2-dG (R.E. Kozack and E.L.Loechler, accompanying paper),
      which is the major benzo[a]pyrene (B[a]P) adduct. Sixteen classes of
      conformations were identified, and are analyzed herein vis-a-vis the two most
      prominent B[a]P mutations, G-->T and G-->A base substitutions. Eight
      conformations seem more relevant to frameshift mutagenesis, so they are excluded,
      leaving eight conformations as follows. Two conformations (BPmi5 and BPmi3)
      retain Watson-Crick G:C base pairing having the B[a]P moiety of the adduct in the
      minor groove. Two conformations (BPma5 and BPma3) have the Hoogsteen orientation
      with B[a]P in the major groove. Four conformations are base displaced and have
      B[a]P stacked in the helix with the dG moiety of the adduct displaced into either
      the major groove (Gma5 and Gma3) or the minor groove (Gmi5 and Gmi3). Three of
      these eight conformations (BPma5, BPma3 and Gma3) are universally high in energy.
      The two conformations that retain G:C base pairing potential (BPmi5 and BPmi3)
      are likely to be non-mutagenic. Of the three remaining conformations, Gmi5 can be
      relatively low in energy, but is distorted. A correlation exists between the
      calculated energies for the remaining two base displaced conformations and
      mutagenesis for [+ta]-B[a]P-N2-dG, leading to the hypothesis that Gma5 is
      responsible for G-->T mutations and Gmi3 is responsible for G-->A mutations. Gma5
      and Gmi3 resemble each other, except that dG is in the major and minor grooves,
      respectively. An incipient rationale for this hypothesis is discussed: DNA
      polymerase might be triggered to follow a different mutagenic pathway depending
      upon whether a non-informational lesion has bulk protruding into the major or
      minor groove. A pathway for interconversion between these eight conformations is
      also proposed and its implications are discussed; e.g. four steps are required to
      interconvert between Gma5 and Gmi3.

PMID- 9934856
TI  - Expression of the inactive C145A mutant human O6-alkylguanine-DNA
      alkyltransferase in E.coli increases cell killing and mutations by N-methyl-N'
      nitro-N-nitrosoguanidine.
AB  - Human O6-alkylguanine-DNA alkyltransferase (AGT) counteracts the mutagenic and
      toxic effects of methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) by removing the methyl group from O6-methylguanine lesions in DNA. The
      methyl group is transferred to a cysteine acceptor residue in the AGT protein,
      which is located at residue 145. The C145A mutant of AGT in which this cysteine
      is converted to an alanine residue is therefore inactive. When this C145A mutant
      was expressed in an Escherichia coli strain lacking endogenous alkyltransferase
      activity, the number of G:C-->A:T mutations actually increased and the toxicity
      of the MNNG treatment was enhanced. These effects were not seen when an E.coli
      strain also lacking nucleotide excision repair (NER) was used. The enhancement of
      mutagenesis and toxicity of MNNG produced by the C145A mutant AGT was not seen
      with another inactive mutant Y114E that contains a mutation preventing DNA
      binding, and the double mutant C145A/Y114E was also ineffective. These results
      suggest that the C145A mutant AGT binds to O6-methylguanine lesions in DNA and
      prevents their repair by NER. The inactive C145A mutant AGT also increased the
      number of A:T-->G:C transition mutations in MNNG-treated cells. These mutations
      are likely to arise from the minor methylation product, O4-methylthymine.
      However, expression of wild-type AGT also increased the incidence of these
      mutations. These results support the hypothesis that mammalian AGTs bind to O4
      methylthymine but repair the lesion so slowly that they effectively shield it
      from more efficient repair by NER.

PMID- 9934857
TI  - The mutagenicity of benzo[a]pyrene in mouse small intestine.
AB  - We have investigated the mutagenicity of benzo[a]pyrene (B[a]P) in small
      intestine using the Dlb-1 locus assay in the mouse. Administration of B[a]P by
      the oral and i.p. routes had markedly different effects on the number of Dlb-I
      mutations and the pattern of induction of cytochrome P-4501A1 (CYP1A1). In Ahr
      responsive animals i.p. injection resulted in marked induction in crypt cells
      along the length of the small intestine, with some induction in the villus cells.
      In contrast, after oral administration, CYP1A1 induction was evident only in the
      villus cells, and this declined distally. The intensity and speed of induction in
      Ahr-responsive animals was such that the genotoxic effect of a single injection
      of B[a]P could not be augmented by prior treatment with non-genotoxic inducers
      such as beta-napthoflavone and TCDD. Oral B[a]P treatment resulted in a decrease
      in the number of mutations when compared with the i.p. route. Studies in congenic
      Ahr-non-responsive versus Ahr-responsive mice indicated that induction of CYP1A1
      was associated with increased numbers of Dlb-1 mutations. Mutation induction in
      Ahr-non-responsive mice in the absence of detectable CYP1A1 in either liver or
      small intestine indicates that an appreciable portion of B[a]P activation to a
      genotoxin must be by other than a CYP1A1 mediated route. These data show that
      B[a]P is a potent small intestinal mutagen at the Dlb-1 locus.

PMID- 9934858
TI  - 3,3'4,4'-Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity
      in the rodent uterus and mammary cells and in human breast cancer cells.
AB  - 3,3',4,4'-Tetrachlorobiphenyl (tetraCB) binds to the aryl hydrocarbon receptor
      (AhR), and several reports have demonstrated that AhR agonists exhibit
      antiestrogenic and antitumorigenic activities in human breast cancer cells, the
      rodent uterus and breast. In contrast, a recent study showed that 3,3',4,4'
      tetraCB bound the estrogen receptor (ER) and exhibited ER agonist activities, and
      we therefore have reinvestigated the estrogenic and antiestrogenic activities of
      3,3',4,4'-tetraCB. Our results showed that 3,3',4,4'tetraCB and a structurally
      related analog, 3,3',4,4',5-pentaCB, did not bind the mouse uterine or human ER,
      did not induce proliferation of MCF-7 or T47D human breast cancer cells or induce
      reporter gene activity in cells transfected with E2-responsive constructs derived
      from the creatine kinase B (pCKB) or cathepsin D (pCD) gene promoters. Moreover,
      3,3',4,4'-tetraCB and 3,3',4,4',5-pentaCB did not induce an increase in uterine
      wet weight, peroxidase activity or progesterone receptor binding in the 21-25-day
      old female B6C3F1 mouse uterus. In contrast, both compounds inhibited 17beta
      estradiol (E2)-induced cell proliferation and transactivation in MCF-7/T47D cells
      and uterine responses in B6C3F1 mice; surprisingly inhibition of E2-induced
      reporter gene activity was not observed in T47D cells transfected with pCKB, and
      this was observed as a cell-specific response with other AhR agonists.
      Additionally, 3,3',4,4'-tetraCB significantly inhibited mammary tumor growth in
      female Sprague-Dawley rats initiated with 7,12-dimethylbenzanthracene. Our
      results indicate that 3,3',4,4'-tetraCB does not exhibit ER agonist activity but
      exhibits a broad spectrum of antiestrogenic responses consistent with ligand
      mediated AhR-ER crosstalk.

PMID- 9934859
TI  - Kinetics of induction of DNA adducts, cell proliferation and gene mutations in
      the liver of MutaMice treated with 5,9-dimethyldibenzo[c,g]carbazole.
AB  - 5,9-Dimethyldibenzo[c,g]carbazole (DMDBC) is a synthetic derivative of the
      environmental pollutant 7H-dibenzo[c,g]carbazole. DMDBC is a potent genotoxic
      carcinogen specific for mouse liver. Using the MutaMouse lacZ transgenic mouse
      model and a positive selection assay, we measured lacZ mutant frequency (MF) in
      the liver 28 days after a single s.c. administration of DMDBC at 3, 10, 30, 90 or
      180 mg/kg. MF remained low at 3 and 10 mg/kg, but increased markedly from 30
      mg/kg onwards. To investigate the reason for this non-linear response, we
      examined mechanisms potentially involved in mutation induction in the liver.
      Genotoxic effects such as DNA adduct formation were detected in 32P-post
      labelling studies. Liver sections were examined for microscopic changes and cell
      proliferation. These parameters, and MF, were studied 2, 4, 7, 14, 21 and 28 days
      after a single s.c. administration of 10 or 90 mg/kg DMDBC. At 10 mg/kg, a dose
      found to double the MF on day 28, DNA adducts reached a level of 200-600 adducts
      per 10(8) nucleotides from day 4 to day 28. No changes in histology or cell
      proliferation were detected at this low dose. At 90 mg/kg, MF increased gradually
      from day 7 to day 28 (maximum 44-fold). The DNA adduct level ranged from 400 to
      4500 adducts per 10(8) nucleotides on day 2, then stabilized at approximately 400
      adducts per 10(8) nucleotides on day 4. An early cytotoxic effect was detected
      microscopically in centrilobular hepatocytes, and was followed by liver cell
      proliferation. These data suggest that the marked increase in MF in MutaMouse
      liver after treatment in vivo with DMDBC at 90 mg/kg may be explained by the
      induction of replicative DNA synthesis due to a cytotoxic effect, allowing the
      fixation of persistent DNA adducts into mutations.

PMID- 9934860
TI  - Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai
      cigarettes: a risk factor for lung cancer and a suspected risk factor for liver
      cancer in Thailand.
AB  - In Thailand, smoking of commercial cigarettes and of handmade cigarettes has
      drastically increased in recent decades. Cancer of the lung and of the upper aero
      digestive tract have also increased in Thailand as they have in many other
      countries. It is our working hypothesis that the increase of primary cancer of
      the liver, especially of cholangiocarcinoma in the north-eastern provinces of
      Thailand is associated with the use of tobacco in men infested with the liver
      fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile
      nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in
      laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine
      in hamsters is significantly increased by infestation with the liver fluke OV.
      The endogenous formation of nitrosamines is significantly increased by OV
      infestation. This report presents analytical data on the concentration of
      volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of
      nine leading brands of commercially produced Thai cigarettes which represent
      approximately 85% of the market share in Thailand. Observed ranges (ng/cigarette)
      were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2
      18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared
      with the smoke of light and blended cigarettes from North America and Western
      Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for
      nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
      There was a correlation between volatile and tobacco-specific nitrosamines, and
      tar and nicotine deliveries in the mainstream smoke. The analytical data are in
      line with the rate for lung cancer and support our working hypothesis that
      nitrosamines, and especially the tobacco-specific nitrosamines, are associated
      with the increased risk for primary liver cancer among those Thai people who
      smoke cigarettes and also carry OV infestation.

PMID- 9934861
TI  - Effects of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on
      human small airway epithelial cells and the protective effects of myo-inositol.
AB  - Benzo[a]pyrene (B[a]P), a tobacco-derived carcinogen, induces lung tumors in
      rodents through its carcinogenic metabolite, anti-7,8-dihydroxy-9,10-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE). Tumorigenesis is inhibited by
      dietary myo-inositol in the post-initiation phase. However, little is known about
      how B[a]PDE and myo-inositol affect normal human lung cells. We addressed this
      question using untransformed human small airway epithelial (SAE) cells. SAE cell
      viability decreased <50% in parallel to an increase of apoptotic cells (>20%) 2
      days after the cells were treated for 1 h with B[a]PDE (>100 nM). In contrast,
      the cell number and viability were not altered in A549 human lung cancer cells by
      B[a]PDE treatment up to 10 microM with <5% apoptotic cells and <10 U/l LDH in the
      medium. SAE cells retain the features of basal cells in serum-free, low Ca2+ (4
      nM) medium up to 4-5 passages, but in serum-supplemented or serum-free, high Ca2+
      (1 mM) cultures, they differentiate into non-ciliated epithelial cells expressing
      Clara cell secretory protein (CCSP). A non-toxic, physiologically relevant dose
      of B[a]PDE (1 nM) partially inhibited serum and Ca2+-induced SAE cell
      differentiation. This effect was abolished by wortmannin, a phosphatidylinositol
      3 kinase (PI-3K) inhibitor, and PD98059, a mitogen activated protein kinase
      (MAPK) kinase-1 (MEK1) inhibitor, but not by SB202190, a p38 MAPK inhibitor, or
      melittin, a protein kinase C inhibitor. Myo-inositol (10-100 microM) did not
      alter growth or differentiation of untreated SAE or A549 cells, but reversed the
      inhibitory effect of B[a]PDE on serum and Ca2+-induced SAE cell differentiation
      when supplemented to the culture after B[a]PDE treatment. This myo-inositol
      action was not altered by PD98059, wortmannin or melittin, but was partially
      suppressed by SB202190. Collectively, these results indicate that B[a]PDE
      inhibits serum-induced SAE cell differentiation, possibly involving activating
      signals through a PI-3K/MEK1 mediated MAPK pathway, whereas myo-inositol protects
      SAE cells against this inhibitory effect of B[a]PDE perhaps through both PI
      3K/MEK1 and p38 MAPK pathways.

PMID- 9934862
TI  - Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies.
AB  - The arene dioxides of five 1-substituted pyrenes have been synthesized using
      dimethyldioxirane. The diasteroisomeric distribution of the dioxides has been
      determined. X-ray crystallographic structures of the dioxides have also been
      obtained. These structures show that for the cis dioxides the molecular
      structures show a departure from planarity, the extent of which is dependent on
      the substituent.

PMID- 9934863
TI  - Alpha-hydroxytamoxifen, a genotoxic metabolite of tamoxifen in the rat:
      identification and quantification in vivo and in vitro.
AB  - The metabolic formation of a-hydroxytamoxifen, a reactive metabolite of tamoxifen
      in rat liver, was characterized and quantified in vitro (hepatic microsomal
      incubations) and in vivo (bile-duct cannulated animals). This minor metabolite
      was identified by chromatographic and mass spectral comparisons with the
      authentic compound. The rates of formation of alpha-hydroxytamoxifen in
      incubations (30 min) of tamoxifen (25 microM) with liver microsomal preparations
      from women (pool of six), female CD1 mice or female Sprague-Dawley rats, as
      quantified by liquid chromatography-mass spectrometry (LC-MS), were 1.15+/-0.03,
      0.30+/-0.05 and 2.70+/-0.35 pmol/min/mg protein, respectively. Selective
      inhibition of microsomal P450 indicated that alpha-hydroxylation was catalysed
      predominantly by CYP3A in humans. Bile-duct cannulated and anaesthetized female
      rats and mice given [14C]tamoxifen (43 micromol/kg, i.v.) excreted, respectively,
      24 and 21% of the administered radioactivity in bile over 5 and 3.5 h. The major
      radiolabelled biliary metabolite in rats, characterized by LC-MS after enzymic
      hydrolysis of conjugates, was the glucuronide of 4-hydroxytamoxifen (10% of dose)
      and only 0.1% of the dose was recovered as alpha-hydroxytamoxifen. After
      administration of alpha-hydroxytamoxifen (43 micromol/kg, i.v.) to rats, only
      1.19% of the administered compound was recovered from a glucuronide metabolite in
      bile, indicating a possible 0.84% alpha-hydroxylation of tamoxifen in vivo. There
      was, however, no indication of the presence in bile of either O-sulphonate or
      glutathione conjugates derived from alpha-hydroxytamoxifen. This study shows for
      the first time that alpha-hydroxytamoxifen can be glucuronylated in rat liver.
      Whereas sulphonation results in electrophilic genotoxic intermediates,
      glucuronidation may represent a means of detoxifying alpha-hydroxytamoxifen.

PMID- 9934864
TI  - Enhancement of glutathione S-transferase placental-form positive liver cell foci
      development by microcystin-LR in aflatoxin B1-initiated rats.
AB  - The objective of this study was to elucidate whether microcystin-LR (MC-LR), a
      hepatotoxic blue-green algal toxin in drinking water, is carcinogenic or
      possesses the ability to modulate aflatoxin B1 (AFB1)-induced
      hepatocarcinogenicity. In a medium-term liver bioassay, male Fischer 344 rats
      were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg)
      followed by an i.p. injection of MC-LR for 6 weeks after 2 weeks of DEN
      treatment. To study the synergism between AFB1 and MC-LR, DEN-treated rats were
      given an i.p. injection of AFB1 (0.5 mg/kg) dissolved in dimethyl sulfoxide
      (DMSO) followed by MC-LR at 2 weeks after the treatment. In a separate
      experiment, the rats were first given AFB1 (0.5 mg/kg) and 2 weeks later an i.p.
      injection of 1 or 10 microg/kg of MC-LR twice a week for 6 weeks. Most rats were
      subjected to a two-thirds partial hepatectomy (PH) at week 3 and were killed
      under anesthesia at week 8. Liver sections were analyzed for glutathione S
      transferase placental form (GST-P) expression, and subjected to histopathological
      examination for phenotypic alteration of hepatocellular foci. In rats that did
      not receive DEN, MC-LR did not cause a significant increase in the numbers of GST
      P-positive foci, whereas AFB1 induced a slight increase in GST-P-positive foci
      development. In rats given DEN, MC-LR enhanced the expression of GST-P-positive
      foci, as did AFB1 but no synergism was observed. Histopathological analysis
      revealed that the area of eosinophilic foci, a biomarker for preneoplastic liver
      lesion, markedly increased because of MC-LR. In rats given AFB1 as an initiator,
      treatment with MC-LR resulted in a synergistic increase in the development of GST
      P-positive foci. These results suggest that the hepatocarcinogenicities of MC-LR
      and AFB1 can be predicted in experimental animals with a medium-term bioassay.
      Furthermore, tumor promoting activity of MC-LR was demonstrated in rats treated
      with AFB1.

PMID- 9934865
TI  - Formation of s-triazines during aerial oxidation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine in concentrated ammonia.
AB  - After automated DNA synthesis, oligodeoxynucleotides containing 8-oxoguanine are
      sensitive to aerial oxidation when subjected to the basic conditions necessary
      for deprotection and release of the oligomer from the control pore glass support.
      The major oxidation products of this heterocyclic moiety have been characterized
      by permitting 8-oxo-7,8-dihydro-2'-deoxyguanosine to react with oxygen in the
      presence of 28% aqueous ammonia at room temperature. Products were isolated by
      reverse phase HPLC and analyzed by electrospray ionization-mass spectrometry and
      gas chromatography-mass spectrometry of the trimethylsilyl-derivatives. 2-Amino-4
      hydroxy-s-triazine-6-carboxylic acid and 2-amino-4-hydroxy-6-carbamyl-s-triazine
      were identified by these techniques and standards were synthesized. In addition,
      GC-MS analysis revealed other oxidation products, including urea, guanidine and 2
      deoxyribose, which were not observed by HPLC because these compounds are
      transparent in the UV region of the spectrum. Both s-triazines were also observed
      when a purified, synthetic oligodeoxynucleotide containing a single 8-oxoguanine
      moiety was exposed to the same conditions. Oxidation of 8-oxoguanine appears to
      parallel the uric acid oxidation pathway, and a mechanistic scheme is proposed to
      account for the products of degradation.

PMID- 9934866
TI  - Promoting effects of kojic acid due to serum TSH elevation resulting from reduced
      serum thyroid hormone levels on development of thyroid proliferative lesions in
      rats initiated with N-bis(2-hydroxypropyl)nitrosamine.
AB  - In order to examine whether kojic acid (KA) exerts a promoting effect on thyroid
      carcinogenesis, male F344 rats were initiated with N-bis(2
      hydroxypropyl)nitrosamine (BHP; 2800 mg/kg body wt, single s.c. injection) and,
      starting 1 week later, received pulverized basal diet containing 2 or 0% KA for
      12 weeks. Untreated control rats were given basal diet for 13 weeks. As an
      additional experiment, two groups without BHP initiation received basal diet or
      diet containing 2% KA for 20 weeks. The serum triiodothyronine (T3) and thyroxine
      (T4) levels were significantly decreased (half to one-third of values of the BHP
      alone group) and serum thyroid-stimulating hormone (TSH) was markedly increased
      (13-19 times higher than the values of the BHP-alone group) in the BHP + KA group
      at weeks 4 and 12. Similar changes in serum thyroid-related hormones were
      observed in the group with 2% KA alone at week 4, but not at week 20. Thyroid
      weights were significantly increased in the BHP + KA and KA-alone groups. Focal
      thyroid follicular hyperplasias and adenomas were observed in 4/5 and 3/ 5 rats
      in the BHP + KA group at week 4, respectively. At weeks 12, these lesions were
      observed in all rats in the BHP + KA group. Animals of the KA alone group showed
      marked diffuse hypertrophy of follicular epithelial cells at weeks 4 and 20. No
      changes in thyroid-related hormone levels or thyroid histopathological lesions
      were observed in either the BHP alone or the untreated control groups.
      Measurement of liver T4-uridine diphosphate glucuronosyltransferase (UDP-GT)
      activity at week 4 revealed no significant intergroup differences. These results
      suggest that thyroid proliferative lesions were induced by KA administration due
      to continuous serum TSH stimulation through the negative feedback mechanism of
      the pituitary-thyroid axis, with decreases of T3 and T4 caused by a mechanism
      independent of T4-UDP-GT activity.

PMID- 9934867
TI  - Poly(ADP-ribose) polymerase activity is not affected in ataxia telangiectasia
      cells and knockout mice.
AB  - Poly(ADP-ribose) polymerase (PARP) is a constitutive factor of the DNA damage
      surveillance network in dividing cells. Based on its capacity to bind to DNA
      strand breaks, PARP plays a regulatory role in their resolution in vivo. ATM
      belongs to a large family of proteins involved in cell cycle progression and
      checkpoints in response to DNA damage. Both proteins may act as sensors of DNA
      damage to induce multiple signalling pathways leading to activation of cell cycle
      checkpoints and DNA repair. To determine a possible relationship between PARP and
      ATM, we examined the PARP response in an ATM-null background. We demonstrated
      that ATM deficiency does not affect PARP activity in human cell lines or Atm
      deficient mouse tissues, nor does it alter PARP activity induced by oxidative
      damage or gamma-irradiation. Our results support a model in which PARP and ATM
      could be involved in distinct pathways, both effectors transducing the damage
      signal to cell cycle regulators.

PMID- 9934868
TI  - Re: Yang, J. and Duerksen-Hughes, P. (1998) A new approach to identifying
      genotoxic carcinogens: p53 induction as an indicator of genotoxic damage.
      Carcinogenesis, 19, 1117-1125.

PMID- 9934869
TI  - PEEP in the prone position: reversing the perfusion imbalance.

PMID- 9934870
TI  - Crystalloids, colloids, and fluid compartments.

PMID- 9934871
TI  - Accounting from Hong Kong.

PMID- 9934872
TI  - The influence of prognosis on care decisions in the critically ill.

PMID- 9934873
TI  - A question of balance.

PMID- 9934874
TI  - Terminal weaning from mechanical ventilation.

PMID- 9934875
TI  - Antidotal flumazenil use--the protamine of the 90s.

PMID- 9934876
TI  - Pulmonary surfactant in acute lung injury.

PMID- 9934877
TI  - Stress ulcer prevention and histamine-2-receptor antagonists: leaps of faith or
      back to the drawing board?

PMID- 9934878
TI  - Evaluating outcome: medical and economic.

PMID- 9934879
TI  - Research on stress ulcer prophylaxis: wrong questions, wrong answers?

PMID- 9934880
TI  - Intratracheal pulmonary ventilation in neonatal respiratory failure.

PMID- 9934881
TI  - Whither pentoxifylline?

PMID- 9934882
TI  - Pulmonary blood flow and flow-dependent metabolic function during acute lung
      injury: recruitment for better or worse?

PMID- 9934883
TI  - Treatment of increased microvascular permeability following inflammation?

PMID- 9934884
TI  - Hepatic arginine metabolism: major questions remain unanswered.

PMID- 9934885
TI  - Airway management during cardiopulmonary resuscitation: a shifting paradigm.

PMID- 9934886
TI  - Mechanics and energetics of tumor necrosis factor-alpha in the left ventricle.

PMID- 9934887
TI  - Surfactant replacement in acute lung injury--the saga continues.

PMID- 9934888
TI  - Pediatric sedation withdrawal: recognizing the need for refinement in a necessary
      therapy.

PMID- 9934889
TI  - Crystalloid-colloid controversy revisited.

PMID- 9934890
TI  - To replace or not to replace vitamins and minerals in CVVH: This is the question.

PMID- 9934891
TI  - Positive end-expiratory pressure redistributes perfusion to dependent lung
      regions in supine but not in prone lambs.
AB  - OBJECTIVE: To examine the influence of positive end-expiratory pressure (PEEP)
      and posture on the distribution of pulmonary blood flow. DESIGN: Experimental
      study. SETTING: University animal laboratory. SUBJECTS: Seven anesthetized and
      mechanically-ventilated lambs. INTERVENTIONS: Four conditions were studied in
      random order: prone or supine position, with or without 5 cm H2O PEEP.
      MEASUREMENTS AND MAIN RESULTS: The distribution of pulmonary blood flow was
      assessed using fluorescent-labeled microspheres (15 microm) in small
      (approximately 1.7 cm3) lung regions. Pulmonary blood flow heterogeneity was
      evaluated using the coefficient of variation of blood flow of the lung regions.
      The number of regions analyzed were 1290+/-154 (SD) per animal. PEEP increased
      pulmonary blood flow heterogeneity in the supine position (47.0+/-7.7% to 54.1+/
      7.3%, p < .01, paired Student's t-test), but not in the prone position (40.4+/
      8.1% to 39.6+/-11.5). Dorsal to ventral (gravitational) flow gradients were
      present only in the supine position, and increased with PEEP (-7.2%/cm vs. -10.4%
      cm, p< .001). CONCLUSIONS: PEEP redistributes pulmonary perfusion to dependent
      lung regions in supine, but not in prone, anesthetized and mechanically
      ventilated sheep.

PMID- 9934892
TI  - Distribution of normal saline and 5% albumin infusions in septic patients.
AB  - OBJECTIVE: To determine the relative distribution of fluid within the
      extracellular fluid volume (ECFV) after infusing either normal saline or 5%
      albumin in septic, critically ill patients. DESIGN: Prospective, randomized,
      unblinded, interventional study. SETTING: Intensive care unit in a 450-bed,
      tertiary care, teaching hospital. PATIENTS: Septic, critically ill patients (n =
      18). INTERVENTIONS: Infusion of either normal saline or 5% albumin to a
      hemodynamic end point determined by the patient's clinician. MEASUREMENTS AND
      MAIN RESULTS: Plasma volume (PV), ECFV, cardiac index, and arterial oxygen
      content were measured immediately before (baseline) and after each fluid
      infusion. PV and ECFV were measured by dilution of 131I-albumin and 35S sodium
      sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV -
      PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ
      between treatment groups. Infusion of normal saline increased the ECFV by
      approximately the volume infused, and the expansion of the PV to ISFV was in a
      ratio of 1:3. Infusion of 5% albumin increased the ECFV by double the volume
      infused, with both the PV and ISFV expanding by approximately equal amounts.
      Oxygen delivery index did not increase after either infusion due to the effect of
      hemodilution. CONCLUSION: Expansion of the ECFV in excess of the volume of 5%
      albumin infused suggests that fluid may move from the intracellular fluid volume
      to the ECFV in septic patients who receive this fluid.

PMID- 9934893
TI  - Long-term outcome and functional health status following intensive care in Hong
      Kong.
AB  - OBJECTIVES: To assess mortality and functional health status of patients at 1 yr
      following admission to a multidisciplinary intensive care unit (ICU) in Hong
      Kong. To determine which factors are associated with a poor long-term outcome.
      DESIGN: Prospective data collection and review. SETTING: A 14-bed
      multidisciplinary ICU in a 1,400-bed tertiary care university hospital. PATIENTS:
      Data from 2,268 consecutive patients admitted over a 2.5-yr period was analyzed,
      including follow-up at 1 yr in 853 adult survivors. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The patients' clinical details and Acute
      Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on day
      2 of admission and reviewed at time of discharge or death. The mean APACHE II
      score on admission was 18. Survival status at 1 yr was ascertained and the
      sickness impact profile (SIP) scored as a measure of functional health status for
      survivors. Sixty-five percent of patients survived to discharge from hospital and
      44% of patients were known to survive to 1 yr; 6% of patients could not be traced
      at 1 yr. Functional health status was assessed in 85% of eligible adult patients.
      Survivors to 1 yr were younger than nonsurvivors and had lower APACHE II scores.
      The median SIP score was 5.1, (25th and 75th percentiles: 0 to 15), and 76% of
      patients had SIP scores < or = 15, i.e., normal health to moderate disability.
      Five percent of the patients were not working or had retired for health-related
      reasons. Stepwise logistic regression to identify factors associated with poor
      functional health status defined as a SIP score >15 at 1 yr found increasing age,
      cardiac/ respiratory arrest, intracranial hemorrhage, and trauma to be associated
      with poor outcomes. A correlation was found between APACHE II scores and SIP
      scores (Spearman's correlation coefficient = 0.13, p < .001). CONCLUSIONS: The
      SIP scores indicated that the majority of patients who survived to 1 yr after ICU
      admission enjoyed reasonable functional health status. A poor functional health
      status at 1 yr did not relate to the severity of the acute illness suffered, but
      appeared to relate to the prognosis of the underlying disease process.

PMID- 9934894
TI  - Effects of prognosis, perceived benefit, and decision style on decision making
      and critical care on decision making in critical care.
AB  - OBJECTIVE: To assess the effects of prognostic estimates, perceived benefit of
      treatment, and practice style on decision-making in critical care. DESIGN:
      Randomized assignment of subjects to either of two versions of a questionnaire
      designed to elicit treatment decisions for six intensive care unit cases based on
      actual patients. One version offered optimistic survival forecasts; the other,
      pessimistic forecasts. SUBJECTS: A random sample of 120 clinicians obtained from
      the Canadian Critical Care Society was contacted by mail. One version of the
      questionnaire was randomly assigned and mailed to each. Thirty-four replies, 17
      for each version (response rate, 28%), were received and analyzed. MEASUREMENTS
      AND MAIN RESULTS: A list of treatment/management options was developed for each
      case, in three categories: recommended, questionable, and unacceptable. Subjects
      were also able to list new options that they would order that were not on the
      list. The dependent variables were the number of actions ordered in each category
      and the total for each case. Perceived benefit was measured by comparing
      subjective estimates of the probability of survival with the
      optimistic/pessimistic forecast given in the case. Practice style was assessed by
      correlating the total number of actions ordered across all possible pairs of
      cases. There were no significant differences between the two questionnaires on
      actions ordered either by category or by amount per category. Perceived benefit
      did not appear to be an important factor in decision-making. However,
      statistically significant correlations provide evidence for practice style in
      intensive care unit decision-making on an interventionist/noninterventionist
      dimension. CONCLUSIONS: There is no evidence that erroneous or biased prognostic
      estimates affect intensive care unit treatment choices. Neither the principle of
      maximizing expected utility nor the Rule of Rescue appear to affect these
      decisions systematically, but practice style does.

PMID- 9934895
TI  - T-cell reactivity and its predictive role in immunosuppression after burns.
AB  - OBJECTIVE: To obtain further insight into the constitutional, phenotype-dependent
      changes of T-helper-1 and T-helper-2 signature lymphokine synthesis after trauma.
      DESIGN: Prospective, descriptive study. SETTING: Intensive care unit of a burn
      center in a community hospital. PATIENTS: Ten patients 1, 3, 5, and 7 days after
      major burn injury and 15 healthy individuals. INTERVENTIONS: Peripheral blood
      mononuclear cells were separated and incubated (5 hrs) for cytokine production
      induced by the accessory cell-independent stimulus of ionomycin and phorbol 12
      myristate 13-acetate. After fixation and permeabilization, cell samples were
      immunofluorescently stained for cell surface antigens (CD4 and CD8),
      intracellular interferon (IFN)-gamma, and interleukin (IL)-4 synthesis. Results
      were correlated with corresponding enzyme-linked immunosorbent assay measurements
      of the culture supernatants. MEASUREMENTS AND MAIN RESULTS: The phenotypic
      analysis of the composition of the helper (CD4) and suppressor/cytotoxic (CD8) T
      cell subset demonstrated that patients suffering from major burns and healthy
      controls express these antigens in similar percentages. The ratio of CD4 positive
      to CD8 positive/CD16 negative T-cell subsets showed no significant changes after
      trauma compared with controls. The production of IL-4 was excessively up
      regulated while the release of IFN-gamma was only slightly increased. The
      predominant cell source of IL-4 after burn trauma was the CD8+ cell with nearly
      five-fold increased production on day 5 (7.2+/-2.6%) vs. 1.5+/-0.4% in controls.
      While CD8+ cells are also capable of enhancing their IFN-gamma synthesis under
      stress by about 60% due to the significant participation of the naive CD45RA+
      subset, the CD4+ IFN-gamma release remained largely unchanged. With this study,
      we demonstrated that in nonsurvivors the number of CD8+ IL-4-producing cells was
      significantly higher compared with controls; also, the number of IFN-gamma
      releasing memory/effector CD45RO+ cells was lower compared with survivors.
      CONCLUSIONS: In previous experiments, we show that a shift to T(H)2 dominated
      phenotypes increases the risk for postburn infection. The current study confirms
      that major burns induce a significant shift of cytokine response in the T(H)2
      direction and demonstrates that the CD8+, rather than the CD4+ phenotype, is
      present. Increased IL-4 production is associated with the T(H)2 lymphocyte. These
      diagnostic tests may help to differentiate patients with compensatory anti
      inflammatory response syndrome and immunosuppression from those patients in the
      proinflammatory state associated with the systemic inflammatory response
      syndrome. The profile described in this article is associated with
      immunosuppression and may contraindicate attempts at anti-inflammatory therapy
      for sepsis.

PMID- 9934896
TI  - Patient responses during rapid terminal weaning from mechanical ventilation: a
      prospective study.
AB  - OBJECTIVE: To describe and analyze patient responses to rapid terminal weaning
      from mechanical ventilation. DESIGN: A prospective, descriptive, correlational
      study. SETTING: An urban, university-affiliated, trauma/emergency hospital.
      PATIENTS: A convenience sample of 31 adult patients experiencing withdrawal of
      mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Physiologic (peripheral oxygen saturation, end-tidal CO2, heart rate, and
      respiratory rate) and comfort (electroencephalogram [EEG], Bizek Agitation Scale,
      and the COMFORT scale) measures were collected at baseline, during, and after the
      terminal weaning procedure. Clinical status was measured using the Acute
      Physiology and Chronic Health Evaluation score, Glasgow Coma Scale, and
      PaO2/F(IO2). Duration of survival after the wean inversely correlated with
      illness severity but did not correlate with consciousness, use of
      analgesia/sedation, or pulmonary function. Respiratory rate and oxygen saturation
      changed significantly during the wean but not end-tidal CO2. Patients remained
      comfortable with little or no analgesia/sedation, in a predominantly comatose
      sample. Subjective measures of comfort strongly correlated with objective data
      from bispectral analysis of EEG. CONCLUSIONS: Patients with altered consciousness
      or coma can be kept comfortable during a rapid terminal weaning procedure with
      morphine and benzodiazepines in low doses. Comfort can be reliably evaluated
      using subjective scales.

PMID- 9934897
TI  - Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost
      effectiveness.
AB  - OBJECTIVE: To investigate cost effectiveness of administration of flumazenil to
      patients presenting with suspected acute drug overdose. DESIGN: Double-blind,
      prospective, placebo-controlled randomized study. SETTING: University teaching
      hospital. PATIENTS: Forty-three adults presenting with suspected drug overdose
      and having a Glasgow Coma Scale (GCS) score of <13. Patients with known
      benzodiazepine/tricyclic ingestion were excluded. INTERVENTIONS: Intravenous
      administration of flumazenil (up to 2 mg) or placebo. MEASUREMENTS AND MAIN
      RESULTS: Individual patient costs were assessed and data aggregated for each
      treatment group. Major diagnostic and therapeutic interventions were recorded and
      between group comparisons performed. Clinical response to study drug
      administration was assessed by obtaining pre- and post-drug GCS scores and
      observation of the patient for at least 180 mins for signs of resedation.
      Aggregate cost or number of major diagnostic and therapeutic interventions were
      not different between groups. Patients randomized to the flumazenil group showed
      a marked increase in GCS score (7.4 to 11.8) compared with those in the placebo
      group (8.2 to 8.6). CONCLUSION: Use of flumazenil in intentional drug overdose of
      unknown etiology is not cost effective.

PMID- 9934898
TI  - Compositional, structural, and functional alterations in pulmonary surfactant in
      surgical patients after the early onset of systemic inflammatory response
      syndrome or sepsis.
AB  - OBJECTIVES: Sepsis is one of the most important predisposing factors for the
      development of the acute respiratory distress syndrome (ARDS). Alterations of
      pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is
      known about surfactant in patients with less severe grades of lung injury related
      to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the
      purpose of this study was to characterize endogenous surfactant in surgical
      intensive care patients with sepsis or SIRS. DESIGN: Prospective, observational
      study. SETTING: University-affiliated, interdisciplinary intensive care unit.
      PATIENTS: Eleven patients after major surgery with SIRS or sepsis included within
      12 hrs of onset and 11 controls without infection or lung disease. INTERVENTIONS:
      Operating room and standard intensive care unit management. MEASUREMENTS AND MAIN
      RESULTS: Four serial bronchoalveolar lavage samples (BAL) were recovered over 7
      days from the patients and single BAL samples were obtained from controls. BAL
      cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar
      transition forms, and surface activity were analyzed. Two of 11 patients met
      criteria for acute lung injury and six of the 11 patients met ARDS consensus
      conference criteria but acute lung injury or ARDS was not persistent. The mean
      Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung
      injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL
      neutrophil counts were increased (p< .01), and the ratio of poorly functioning
      light aggregate surfactant to superiorly functioning heavy aggregate surfactant
      was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A
      was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were
      increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p <
      .01), and protein to phospholipid (p < .05). The surface tension-lowering ability
      of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs.
      2.8+/-0.6 milliNewtons/m, p< .05). CONCLUSIONS: These observations show that
      surgical patients with SIRS or sepsis who have mild-to-moderate lung injury
      develop surfactant dysfunction detectable within 7 days of onset. We propose,
      therefore, that therapeutic strategies to modulate these severe surfactant
      abnormalities should be considered, as these strategies may have the potential to
      reduce lung injury, which is associated with a high mortality in sepsis.

PMID- 9934899
TI  - Effect of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of
      mononuclear cells.
AB  - OBJECTIVE: To examine and compare the effects of omeprazole, lansoprazole, and
      ranitidine on the DNA synthesis of peripheral blood mononuclear cells. DESIGN: Ex
      vivo laboratory study. SETTING: Clinical research laboratory of an academic
      medical center. SUBJECTS: Healthy volunteers. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Venous blood was collected from normal subjects and peripheral
      blood mononuclear cells (PBMCs) were isolated using centrifugation techniques
      over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture
      plates in four groups of media: a) control; b) control plus lansoprazole (25
      microg/mL); c) control plus omeprazole (0.35 microg/mL); and d) control plus
      ranitidine (50 microg/mL). PBMCs were exposed to the drug for 96 hrs, with
      addition of phytohemagglutinin (2.5 microg/ mL) for the last 48 hrs, and 3H
      thymidine (1 microCi) during the final 6 hrs. PBMCs were filtered onto glass
      fiber filter paper and the radioactivity was determined by scintillation
      counting. Since radioactivity is measured only in those cells undergoing DNA
      synthesis or cell division, results are expressed as quantification of 3H
      thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well+/
      SEM are reported: control 68.3+/-37.8; ranitidine 38.4 +/-94.2; lansoprazole
      14.6+/-84.4; and omeprazole 15.1+/-48.9. There was a significant difference
      between lansoprazole vs. ranitidine (p< .01), and omeprazole vs. ranitidine (p<
      .05), and no significant difference between lansoprazole and omeprazole.
      CONCLUSIONS: This is the first study to compare the potential immunomodulating
      effects of these commonly used agents. Ranitidine caused increased DNA synthesis
      in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be
      an important, often disregarded, effect of histamine-2-receptor antagonists when
      used in postsurgical or trauma patients who have T-lymphocyte-mediated immune
      suppression.

PMID- 9934900
TI  - Critical care for the severely ill head and neck patient.
AB  - OBJECTIVE: To delineate the frequency and causes of admission to a critical care
      environment for patients undergoing head and neck surgery at Memorial Sloan
      Kettering Cancer Center. DESIGN: Retrospective clinical investigation. SETTING:
      Adult intensive care unit of a tertiary referral cancer center. PATIENTS: All
      head and neck surgery patients admitted to the special care unit (SCU) of
      Memorial Sloan-Kettering Cancer Center between January 1, 1994 and December 31,
      1995 were included in this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The data collected included demographic, operative procedures, clinical,
      laboratory, and physiologic variables at time of SCU admission, at 24 hrs, as
      well as vital status at the time of discharge from the SCU and hospital. Other
      data collected were the need for mechanical ventilation and inotropic agents.
      During the period of January 1, 1994 through December 31, 1995, 37 (1.5%) of
      2,346 patients undergoing head and neck surgical procedures required admission to
      the SCU. During the same period, six patients receiving medical treatment only
      for head and neck malignant disease were transferred to the SCU. These 43
      admissions served as the basis for the study. The causes of admission to the SCU
      were pulmonary (15/43), cardiac (14/43), wound related (8/43), and other (15/43).
      The median length of stay in the SCU was 2 days, and the median hospitalization
      for patients requiring critical care services was 22 days. Seventy-four percent
      of patients requiring critical care services were eventually discharged to home.
      CONCLUSIONS: Current preoperative evaluation, operative and anesthetic
      techniques, and perioperative care result in a low frequency of utilization of
      critical care services by patients undergoing head and neck surgery. There is no
      single identifiable cause of complications for patients after head and neck
      surgery leading to utilization of critical care services.

PMID- 9934901
TI  - National survey of stress ulcer prophylaxis.
AB  - OBJECTIVE: To determine the rationale for using stress ulcer prophylaxis (SUP)
      among clinicians; to assess criteria used to define failure of SUP; and to
      evaluate the decision-making process in the selection of a prophylactic agent.
      DESIGN: A cross-sectional national mail survey. SETTING: Random sample of the
      members of the Society of Critical Care Medicine who identified anesthesiology,
      surgery, or internal medicine as their primary specialty area. PATIENTS: None.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Questionnaires consisting of
      multiple-choice and short-answer questions were sent to a simple random sample of
      1,268 physicians to assess the current practice of SUP. A total of 328 usable
      questions were returned, resulting in a response rate of 26%. All percentages
      reported in the results are based on the total number of responses. The risk
      factors for SUP that were most commonly identified were burns (91%), shock (90%),
      and sepsis (88%). These were also risk factors for which the respondents most
      commonly started SUP. Histamine-2-receptor (H2)-antagonists as a class, were the
      most commonly used prophylactic agents (67%). The most commonly used agents for
      SUP were ranitidine (31%), famotidine (24%), sucralfate (24%), and cimetidine
      (12%). Most respondents selected ranitidine for ease of administration,
      famotidine because of formulary availability, sucralfate for a better side
      effects profile, and cimetidine for cost-effectiveness. Eighty-two percent of
      respondents considered the presence of bright red blood in the nasogastric tube
      as failure of SUP. In cases where SUP failed, most respondents would add a second
      agent from a different therapeutic class. Of those respondents who used an H2
      antagonist initially, 48% would add sucralfate, 36% would add antacid, and 13%
      would add omeprazole. Of those respondents who used sucralfate, 77% would add an
      H2-antagonist when SUP failed. For those respondents who would switch to another
      agent when the H2-antagonist failed, 52% would change to omeprazole, whereas 67%
      would change to an H2-antagonist when sucralfate failed. Only eight respondents
      would discontinue SUP when risk factors were resolved. Most respondents would
      discontinue SUP when the patient was no longer in the "nothing by mouth" status
      (28%), started on enteral feeding (23%), or discharged from the intensive care
      unit (21%). The mean duration of SUP was 6.3+/-4.5 (SD) days. CONCLUSIONS: This
      survey highlighted the lack of consensus in the use of SUP. Many patients receive
      SUP for an extended period, without clear-cut indications or documented benefit.
      The cost of unwarranted SUP in patients with low risk of stress ulcer
      gastrointestinal bleeding is prohibitive. Treatment algorithms or protocols for
      SUP based on prescribing patterns, hospital formulary restrictions, and cost
      analysis should be considered for each institution to guide critical care
      physicians on the proper use of SUP therapies.

PMID- 9934902
TI  - Nosocomial infection following cardiovascular surgery: comparison of two periods,
      1987 vs. 1992.
AB  - OBJECTIVE: To evaluate whether changes have occurred at our center in the rate of
      nosocomial infections and in the infectious organisms consequent to changes in
      policy and procedure as of 1987. SETTING: Multidisciplinary pediatric intensive
      care unit (PICU) in a major tertiary care center. DESIGN: Prospective comparative
      study. PATIENTS: Four-hundred and fifty-five consecutive patients who underwent
      cardiac surgery within a 10-month period. INTERVENTIONS: Changes related to
      antibiotic use and invasive device management were introduced after the 1987
      survey. To determine the effect of these changes, all patients undergoing cardiac
      surgery between July 1991 and April 1992 were followed daily from PICU admission
      to 2 months after hospital discharge for signs of infection. Each infectious
      episode was reviewed by the nosocomial infection control committee. A weighted
      scoring system was used to determine risk. MEASUREMENTS AND MAIN RESULTS: In the
      1987 study, 40 of 310 patients had 78 infections for a nosocomial infection ratio
      (NIR) of 25.2. Of the 455 patients surveyed in 1992, 72 had 91 episodes of
      infection. The nosocomially infected patient rate was 15.8 and the NIR was 20.
      The frequency of wound infection decreased from 7% in 1987 to 4.3% in this study,
      and no episode of mediastinitis was observed. In the bacteriological spectrum,
      the absence of candidal infection was significant, and there was a decrease in
      the proportional frequency of pseudomonas infection from 21% to 15%. CONCLUSION:
      The comparison between the two time periods demonstrates that an aggressive
      approach to managing intravascular catheters and urinary catheters and limiting
      the use of antibiotics probably affects the spectrum of nosocomial infections.

PMID- 9934903
TI  - A new ventilator improves CO2 removal in newborn lambs with congenital
      diaphragmatic hernia.
AB  - OBJECTIVES: To demonstrate improved ventilation with intratracheal pulmonary
      ventilation (ITPV) in new-born lambs with congenital diaphragmatic hernia, using
      a new microprocessor controlled ITPV-specific ventilator. DESIGN: Prospective
      study, with each animal serving as its own control (paired data). SETTING: Large
      animal research laboratory. SUBJECTS: Diaphragmatic hernias were created
      surgically in seven fetal sheep on gestational day 100 (term = 145 days).
      INTERVENTIONS: Lambs (2.7 to 5.0 kg) were delivered by cesarean section anywhere
      between gestational days 136 and 140. Arterial and venous catheterizations,
      bilateral chest tube thoracostomies, and tracheostomies were performed while the
      lambs received placental bypass. Initially, congenital diaphragmatic hernia lambs
      were supported on conventional pressure control mechanical ventilation to achieve
      steady state with measurements of baseline vital signs, arterial blood gases, and
      ventilatory settings. ITPV was instituted while maintaining constant peak carinal
      pressures and oxygen saturations. Statistical comparisons were made using the
      paired t-test. MEASUREMENTS AND MAIN RESULTS: Postductal Paco2 decreased from
      110+/-21 (SD) torr (14.7+/-2.8 kPa) to 52+/-24 torr (6.93+/-3.2 kPa; p= .0014) on
      ITPV. Simultaneously, pH improved from 7.04+/-0.07 to 7.31+/-0.15 (p = .0012) and
      minute ventilation increased from 0.66+/-0.40 to 4.00+/-1.35 L/min (p = .0016).
      Peak carinal pressures and postductal Pao2 were unchanged. CONCLUSIONS: ITPV
      significantly improved CO2 removal in newborn lambs with diaphragmatic hernias
      without increasing airway pressures or changing oxygenation. Based on these
      results, we are conducting human clinical trials.

PMID- 9934904
TI  - Effect of pentoxifylline on survival and intestinal cytokine messenger RNA
      transcription in a rat model of ongoing peritoneal sepsis.
AB  - OBJECTIVE: Septic animals receiving high-protein liquid diets have increased
      mortality and increased production of cytokines by the gut compared with animals
      receiving low-protein diets. The purpose of this study was to evaluate the
      ability of pentoxifylline to alter gut cytokine production in a rat model of
      prolonged acute peritonitis, to determine its effect on survival in such animals,
      and to determine whether alteration of gut cytokine production was associated
      with survival. DESIGN: Prospective, randomized animal study. SETTING: Research
      laboratory. SUBJECTS: Male Lewis rats weighing between 250 and 300 g.
      INTERVENTIONS: Anesthetized rats had placement of a gastrostomy, followed 1 wk
      later by implantation of a bacteria-filled osmotic minipump into the peritoneal
      cavity. Rats were fed a high-protein (20% total energy) enteral diet. Saline or
      pentoxifylline (5 or 20 mg/kg im) was administered daily beginning at the time of
      pump implantation. MEASUREMENTS AND MAIN RESULTS: Septic rats fed the high
      protein liquid diet and given pentoxifylline in a dose of 5 mg/kg/day
      demonstrated improved survival compared with saline-treated animals or animals
      given the high dose (20 mg/kg/day) of pentoxifylline (p< .05). Administration of
      pentoxifylline at 5 mg/kg/day also down regulated the production of IL-6
      messenger RNA (mRNA) in liver and lipopolysaccharide binding protein mRNA in the
      liver and intestine of septic animals given the high-protein liquid diet.
      CONCLUSION: Low-dose (but not high-dose) pentoxifylline administration reduced
      production of some, but not all, cytokines studied in the gut and liver in a rat
      model of acute peritonitis and this reduced production was associated with an
      improved survival in such animals.

PMID- 9934905
TI  - Vascular recruitment increases evidence of lung injury.
AB  - OBJECTIVE: Changes in pulmonary blood flow rate can alter the size of the
      perfused pulmonary capillary surface area. We tested the hypothesis that full
      recruitment of the pulmonary vascular bed may decrease evidence of lung injury by
      recruiting less injured capillaries. We also tested the hypothesis that
      endothelial ectoenzyme activity is an earlier indicator of lung injury than are
      permeability measures. DESIGN: Isolated canine lung lobes were perfused with
      autologous blood at constant blood flows of either 2.05+/-0.04 L/min (SEM) (high
      flow, full recruitment, n = 12) or 0.600 +/- 0.004 L/min (low flow, 33% full
      recruitment, n = 12) after lung injury to determine the effect of vascular
      recruitment on measures of injury. SETTING: Research laboratory at a medical
      university. SUBJECTS: Lung lobes were obtained from 36 mongrel dogs of either
      gender. INTERVENTIONS: Lung injury was induced by adding phorbol myristate
      acetate (PMA) to the blood perfusing the isolated lung. MEASUREMENTS AND MAIN
      RESULTS: Indicator dilution methods were used to measure single pass hydrolysis
      of 3[H]-benzoyl-Phe-Ala-Pro, a synthetic substrate for angiotensin converting
      enzyme, and calculate the modified first order kinetic parameter corresponding to
      the ratio of a normalized maximal enzymatic conversion rate (A(max)) to the
      Michaelis-Menten constant (K(m)), i.e., A(max)/K(m), before and after PMA. At a
      given flow rate, the decrease in A(max)/K(m)serves as an index of vascular
      injury. PMA decreased A(max)/K(m), percent metabolism, and fractional substrate
      utilization, and increased permeability, vascular resistance, and vascular
      pressures regardless of flow rate. The decrease in enzyme activity was detected
      earlier than the increase in permeability. CONCLUSION: The greater percentage
      decrease in percent metabolism and fractional substrate utilization and the
      earlier appearance of increased permeability during high flow indicates that
      increasing blood flow three-fold recruited injured vessels and/or increased
      vascular injury by increasing vascular perfusion pressures.

PMID- 9934906
TI  - Low-dose prostacyclin is superior to terbutaline and aminophylline in reducing
      capillary permeability in cat skeletal muscle in vivo.
AB  - OBJECTIVE: To analyze and compare the capillary permeability-reducing effects of
      prostacyclin, terbutaline, and aminophylline. DESIGN: A prospective, experimental
      study. SETTING: A university laboratory. SUBJECTS: Fourteen adult, anesthetized
      cats. INTERVENTIONS: The study was performed on an autoperfused calf muscle
      preparation enclosed in a plethysmograph, with continuous recordings of tissue
      volume, arterial and venous blood pressures, and blood flow. The capillary
      filtration coefficient was used as a measure of capillary hydraulic permeability,
      and measured at different doses of intravenous infusions of prostacyclin,
      terbutaline, and aminophylline. These analyses were made from normal and from
      raised permeability levels, the latter by prior and simultaneous infusion of
      tumor necrosis factor-a (TNF-a) or histamine. All three of the drugs analyzed
      were given at low doses, without vasodilator effect, and at doses with a clear
      vasodilator effect. MAIN RESULTS: Prostacyclin infusion reduced capillary
      permeability to a value of about 25% below the initial control value, and this
      level was reached both from normal and increased permeability levels. The maximal
      reduction level was obtained at a low nonvasodilator dose of 2 ng/kg/min.
      Terbutaline and aminophylline had no significant effect on capillary filtration
      coefficient when tested from the initial control permeability level. From a TNF
      alpha-raised permeability level (about 50% above control) and from a histamine
      raised permeability level (about 60% above control), both drugs induced small
      reductions in the capillary filtration coefficient. CONCLUSION: Low-dose
      prostacyclin effectively reduces hydraulic capillary permeability in cat skeletal
      muscle and is superior to terbutaline and aminophylline.

PMID- 9934907
TI  - Arginine-nitric oxide pathway in plasma membrane of rat hepatocytes during early
      and late sepsis.
AB  - OBJECTIVE: To study the transported L-arginine in rat hepatocytes during
      different stages of sepsis. DESIGN: A prospective, controlled study. SUBJECTS:
      Thirty-six Sprague-Dawley male rats (250 to 300 g) were anesthetized and studied.
      INTERVENTIONS: Early sepsis was produced 9 hrs after cecal ligation and puncture
      (CLP) and late sepsis developed 18 hrs after CLP. The control group underwent
      sham operation. Plasma membrane of rat hepatocytes was prepared by differential
      centrifugation. The [3H] L-arginine uptake of plasma membrane vesicles during
      sepsis was measured and inhibition studies employing omega-nitro-L-arginine
      methyl ester (L-NAME) and aminoguanidine were performed. MEASUREMENTS AND MAIN
      RESULTS: L-arginine transport was saturable, increased linearly with plasma
      membrane protein concentration, and increased with uptake time up to 5 mins. [3H]
      L-arginine uptake increased by 77% to 121% (p < .05) during early sepsis, with no
      significant changes during late sepsis. Comparing inhibitors of nitric oxide
      synthase, L-NAME was effective in inhibiting L-arginine transport while
      aminoguanidine was not. CONCLUSIONS: L-arginine transport was enhanced in rat
      hepatocytes during the early stage of sepsis. The increased uptake of L-arginine
      could contribute to the increase production of nitric oxide by hepatocyte during
      sepsis.

PMID- 9934908
TI  - Aspiration and transtracheal jet ventilation with different pressures and depths
      of chest compression.
AB  - OBJECTIVE: To evaluate aspiration prophylaxis during cardiopulmonary
      resuscitation (CPR) using transtracheal jet ventilation (TJV) with different
      pressure-depths of chest compression and chest compression alone without
      mechanical ventilation. DESIGN: Prospective, animal study. SETTING: Animal
      research laboratory, Chang Gung Memorial Hospital, Kaohsiung Medical Center,
      Taiwan. SUBJECTS: Mongrel dogs (n = 10) weighing 8 to 12 kg. INTERVENTIONS: Eight
      mongrel dogs were anesthetized, paralyzed, and ventilated transtracheally with a
      jet ventilator at frequencies varied from 600 to 10 cycles/min. The airway
      pressures below and above the jetting port were measured. The mouth of the dog
      was filled with barium and chest radiographs were taken 10 mins after chest
      compression with 20-pound pressure and 5-cm depth in group 1 and 10-pound
      pressure and 3-cm depth in group 2 at each different jet frequency. Two
      additional dogs underwent the same procedures but received only chest compression
      without TJV. MEASUREMENTS AND MAIN RESULTS: Pulmonary aspiration was not noted in
      the chest radiographs from either group. The airway pressure changes between
      groups were not significantly affected by difference in pressures and depths of
      chest compression at the same jetting frequency. However, pulmonary aspiration
      occurred in the two dogs that received chest compression alone without TJV.
      CONCLUSIONS: Application of TJV during chest compression with different pressures
      and depths caused no pulmonary aspiration in dogs at frequencies between 600 and
      10 cycles/min. The protection against aspiration disappeared if the dogs received
      only chest compression without TJV. The mechanism of preventing pulmonary
      aspiration in TJV is thought to be due to forceful unidirectional gas outflow
      through the larynx and higher airway pressure in the carina than in the upper
      airway. The airway pressures were not affected by different chest compression
      pressures and depths because the larynx stayed open during TJV and the air
      outflow could freely move out without increasing the pressure in the airway.

PMID- 9934909
TI  - Improvement of renal dysfunction in dogs with endotoxemia by a nonselective
      endothelin receptor antagonist.
AB  - OBJECTIVES: During endotoxemia, there is a marked and intractable decrease in
      systemic blood pressure, as well as profound vasoconstriction of the renal
      artery, thereby leading to septic shock and acute renal failure. The purpose of
      this study was to elucidate the effect of endothelin-1, a potent endothelium
      derived vasoconstrictor peptide, on the hemodynamic and renal vascular changes
      seen in endotoxemia. DESIGN: Prospective, comparative, experimental study.
      SETTING: Laboratory at a university hospital. SUBJECTS: Thirty-two male mongrel
      dogs (12.1+/-0.4 kg) under pentobarbital anesthesia. INTERVENTIONS: Four groups
      of animals were studied: a) the lipopolysaccharide (LPS) group (n = 10), which
      received LPS (250 ng/kg/min for 2 hrs); b) the TAK-044 (a nonselective
      endothelinA/ endothelinB receptor antagonist) plus LPS group (n = 12), which
      received a bolus of TAK-044 (5 mg/kg) 0.5 hr before the start of LPS infusion; c)
      the TAK-044 plus vehicle group (n = 5), which received the same dose of TAK-044
      0.5 hr before the start of vehicle infusion; and d) the control group (n = 5),
      which received only vehicle infusion. MEASUREMENTS AND MAIN RESULTS: Changes in
      systemic and renal hemodynamics, blood gas, and renal function were measured at
      baseline, and at 0.5, 1, 2, 3, and 4 hrs. Infusion of LPS resulted in significant
      decreases in mean arterial pressure, arterial pH, Pao2, base excess, urine
      volume, renal blood flow, creatinine clearance, and urine osmolality. The
      administration of TAK-044 before LPS infusion did not affect the LPS-induced
      hypotension. In contrast, the receptor antagonist prevented LPS-induced metabolic
      acidosis and hypoxemia, and improved LPS-induced decreases in urine volume, renal
      blood flow, creatinine clearance, and urine osmolality, whereas TAK-044 or
      vehicle administered alone resulted in no significant hemodynamic or blood gas
      changes. Plasma endothelin-1 concentrations significantly increased after LPS
      infusion, with or without TAK-044. CONCLUSIONS: The present study suggests that
      endothelin-1 plays an important role in the impaired renal hemodynamics and renal
      function associated with endotoxemia, and that endothelin receptor antagonists
      may be useful as therapeutic agents for acute renal failure during endotoxemia.

PMID- 9934910
TI  - Prognostic value of blood lactate, base deficit, and oxygen-derived variables in
      an LD50 model of penetrating trauma.
AB  - OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived
      hemodynamic variables correlate with morbidity and mortality rates in a
      clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective,
      controlled study. SETTING: University research laboratory. SUBJECTS:
      Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29).
      INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh,
      followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and
      supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND
      MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to
      52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of
      six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5%
      hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the
      LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM
      and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation,
      systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83
      mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline
      preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198
      mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only
      lactate was significantly related to blood loss before and after fluid
      resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to
      .50), which indicates that only a small fraction of the hyperiactacidemia was
      directly related to tissue hypoperfusion. In the whole population of survivors
      and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived
      variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a
      stronger index of blood loss after penetrating trauma than base deficit or oxygen
      derived hemodynamic variables. The reliability of arterial lactate depends on
      several factors, such as the time after injury, the proportion of survivors and
      nonsurvivors in the study population, and on factors other than tissue hypoxia.

PMID- 9934911
TI  - Selective inhibition of inducible nitric oxide synthase: effects on hemodynamics
      and regional blood flow in healthy and septic sheep.
AB  - OBJECTIVES: To investigate the effects of S-ethylisothiourea (S-EITU) on
      hemodynamics, oxygen transport, and regional blood flow in healthy and septic
      sheep. DESIGN: Prospective, randomized, controlled experimental study with
      repeated measures. SETTING: Investigational intensive care unit at a university
      medical center. SUBJECTS: Eleven healthy, female adult sheep of the Merino breed,
      divided into a control group (n = 5) and into a group treated with S-EITU (n =
      6). INTERVENTIONS: All sheep were chronically instrumented. After a 5-day
      recovery period, they were randomly assigned to either control or S-EITU groups.
      While control sheep received only saline, S-EITU was administered in increasing
      doses of 1, 3, and 9 mg/kg/hr over 1 hr each (nonseptic phase). After 2 days of
      recovery, a continuous infusion of live Pseudomonas aeruginosa (2.5 x 106 colony
      forming units/min) was started in all sheep and maintained for the remainder of
      the experiment. After 24 hrs of sepsis, the sheep again received their assigned
      treatment (septic phase). In both the nonseptic and septic phases, the sheep
      received colored microspheres through a left atrial catheter to allow analysis of
      regional blood flows. All animals were autopsied at the end of the experiments,
      and organ probes were removed for blood flow analyses. MEASUREMENTS AND MAIN
      RESULTS: The administration of S-EITU caused a dose-dependent vasoconstriction in
      the nonseptic phase. After 24 hrs of Pseudomonas infusion, all sheep developed a
      hyperdynamic circulatory state, with increased cardiac indices and reduced
      arterial pressures and systemic vascular resistances. Oxygen extraction decreased
      significantly, preventing an increase in oxygen consumption, despite an increased
      oxygen delivery. The hyperdynamic circulation was dose dependently reversed by S
      EITU, causing an increase in arterial pressure by peripheral vasoconstriction.
      Sheep in the control group showed a continuation of the hyperdynamic circulation.
      The effects of S-EITU on hemodynamics and regional blood flows were comparable
      under septic and nonseptic conditions. CONCLUSIONS: With the inducible form of
      nitric oxide synthase expressed under septic, but not under nonseptic conditions,
      S-EITU was expected to have vasoconstrictive properties only in the septic phase.
      It produced a comparable vasoconstriction during the nonseptic phase of the
      experiment. Thus, either S-EITU does not selectively block the inducible nitric
      oxide synthase in sheep, or other vasodilators besides nitric oxide play an
      important role in septic vasodilation.

PMID- 9934912
TI  - Acute effect of tumor necrosis factor-alpha is minimal on mechanics but
      significant on energetics in blood-perfused canine left ventricles.
AB  - OBJECTIVES: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely
      alters left ventricular mechanoenergetics in blood-perfused hearts. To test this
      hypothesis, we examined the relation between left ventricular mechanics and
      energetics, both before and after infusion of TNF-alpha. DESIGN: Prospective,
      experimental study. SETTING: Research laboratory. SUBJECTS: Nine isolated, blood
      perfused canine hearts. INTERVENTIONS: Recombinant human TNF-alpha (90
      microg/min) was infused into the coronary circulation of the isolated hearts for
      20 mins. MEASUREMENTS AND MAIN RESULTS: In the isolated, cross-circulated, blood
      perfused canine left ventricles, left ventricular contractility was assessed
      through measurement of end-systolic elastance (Ees). Energetics were examined in
      terms of the end-systolic pressure-volume area-myocardial oxygen consumption
      (MVo2) relation. TNF-alpha concentration in coronary venous blood was >1000 ng/mL
      throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected
      contractility acutely, i.e., there was a minimal decrease during the infusion
      (8.1+/-2.8% at 10 mins, p < .01) and a minimal increase after the infusion
      (11.2+/-2.5% at 10 mins, p< .01). Neither did the TNF-alpha infusion affect the
      slope of the end-systolic pressure-volume area-MVo2 relation. This finding
      indicated that the chemomechanical conversion efficiency remained unchanged.
      However, TNF-alpha infusion significantly increased the oxygen cost of
      contractility by 40% (1.25+/-0.13 vs. 1.75+/-0.24 mL oxygen.mL/mm Hg/beat, p<
      .05), indicating that MVo2 for the excitation-contraction coupling increased.
      CONCLUSIONS: TNF-alpha minimally alters left ventricular mechanics, but
      significantly changes energetics. The latter effect may result from changes in
      intracellular calcium handling.

PMID- 9934913
TI  - Delayed intracranial hypertension: relationship to leukocyte count.
AB  - OBJECTIVE: Secondary intracranial hypertension has been linked to leukocytosis.
      We examined our data bank containing physiologic recordings and outcome data of
      severely head injured patients to investigate the relationship between delayed
      increases in intracranial pressure (ICP), defined as occurring after a 12-hr
      period of normal ICP values, and leukocytosis. DESIGN: A retrospective study of
      observational data. SETTING: Regional neurosurgical unit and intensive care unit.
      PATIENTS: Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five
      patients fulfilled selection criteria for delayed increases in ICP (group 1).
      Twenty-nine patients with increased ICP with no preceding or intervening periods
      of normal ICP were selected as a comparison group (group 2). MEASUREMENTS AND
      MAIN RESULTS: Comparison of 12-month outcome revealed that 11% of group 1
      patients died, with 49% remaining severely disabled, in contrast to group 2,
      where 35% of patients died and 14% were left severely disabled (p = .021). The
      pattern of outcome was independent of monitoring time, or injury severity.
      Regression modeling was performed for prediction of delayed increase in ICP. Of
      46 patients with an initial increase then decrease in leukocyte count in the
      first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of
      the 11 patients without this pattern p = .01 1). CONCLUSIONS: Patients with
      delayed increases have a significantly different pattern of outcome. Change in
      leukocyte count from admission to day 2 is a significant predictor of such a
      delayed increase.

PMID- 9934914
TI  - Favorable recovery from bilateral loss of somatosensory evoked potentials.
AB  - OBJECTIVES: Bilateral loss of the cortical somatosensory evoked potentials (SEP)
      is usually regarded as a strong predictor for a very poor clinical outcome. We
      present four patients with a favorable recovery from bilaterally absent cortical
      SEP. DESIGN: Case series. SETTING: Neurocritical care unit at the University of
      Heidelberg. PATIENTS: Four patients with viral encephalitis, carbamazepine
      intoxication, head trauma, and left-side, space-occupying hemispheric infarction,
      respectively. INTERVENTIONS: Serial recording of somatosensory and auditory
      evoked potentials, therapy of increased intracranial pressure, including
      decompressive surgery, hypothermia, and barbiturate coma. MEASUREMENTS AND MAIN
      RESULTS: Three patients had an excellent outcome (Glasgow Outcome Scale 4 and 5).
      In those three patients, the SEP became completely normal during the clinical
      course. In one patient who remained severely disabled, the SEP became detectable
      again over the contralateral hemisphere, but remained abnormal. Possible
      influencing factors were sedative and analgetic drugs in all patients, and
      hypothermia and barbiturate coma in one of the patients. CONCLUSIONS: The absence
      of cortical SEP does not invariably imply an unfavorable prognosis. Absent
      cortical SEP indicates a severe neuronal dysfunction, which may be completely
      reversible if the underlying disease does not lead to permanent structural
      damage.

PMID- 9934915
TI  - Instillation of calf lung surfactant extract (calfactant) is beneficial in
      pediatric acute hypoxemic respiratory failure. Members of the Mid-Atlantic
      Pediatric Critical Care Network.
AB  - OBJECTIVE: Prospective study of the efficacy of calf lung surfactant extract in
      pediatric respiratory failure. DESIGN: Multi-institutional, prospective,
      randomized, controlled, unblinded trial. SETTING: Eight pediatric intensive care
      units (ICU) of tertiary medical centers. PATIENTS: Forty-two children with acute
      hypoxemic respiratory failure characterized by diffuse, bilateral pulmonary
      infiltrates, need for ventilatory support, and an oxygenation index of >7.
      INTERVENTION: Instillation of intratracheal surfactant (80 mL/m2). MEASUREMENTS
      AND MAIN RESULTS: Ventilator parameters, arterial blood gases, and derived
      oxygenation and ventilation indices were recorded before and at intervals after
      surfactant administration. Complications and outcome measures, including
      mortality, duration of mechanical ventilation, and length of pediatric ICU and
      hospital stay, were also examined. Patients who received surfactant demonstrated
      rapid improvement in oxygenation and, on average, were extubated 4.2 days (32%)
      sooner and spent 5 fewer days (30%) in pediatric intensive care than control
      patients. There was no difference in mortality or overall hospital stay.
      Surfactant administration was associated with no serious adverse effects.
      CONCLUSIONS: Administration of calf lung surfactant extract, calfactant, appears
      to be safe and is associated with rapid improvement in oxygenation, earlier
      extubation, and decreased requirement for intensive care in children with acute
      hypoxemic respiratory failure. Further study is needed, however, before
      widespread use in pediatric respiratory failure can be recommended.

PMID- 9934916
TI  - Occurrence of withdrawal in critically ill sedated children.
AB  - OBJECTIVES: To record the number of children with withdrawal symptoms after the
      administration of sedatives for mechanical ventilation, and to discuss the
      possible connection with the administration of midazolam. DESIGN: Retrospective
      data collection from case records and charts. SETTING: Medical and surgical
      intensive care unit (ICU) in a university hospital. PATIENTS: Children 6 months
      to 14 yrs of age who required sedation for mechanical ventilation (n = 40).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Kind and amount of sedatives
      and analgesics, duration of administration, and occurrence of withdrawal
      symptoms. The frequency of withdrawal symptoms was 35% (14/40) of the sedated
      children. A total dose of midazolam of >60 mg/kg was strongly significantly
      associated with occurrence of withdrawal. Statistical analysis to determine the
      occurrence of withdrawal associated with the administration of morphine was not
      possible. CONCLUSIONS: Signs and symptoms of a withdrawal reaction were observed
      in several children. The occurrence of withdrawal was statistically related to
      high doses of midazolam, but it was not possible to determine the influence of
      morphine. If large doses of midazolam and opioids have been administered, there
      may be justification for reducing the dose gradually instead of abruptly, or
      using longer-acting benzodiazepines or opioids on discontinuation of sedation.

PMID- 9934917
TI  - Crystalloids vs. colloids in fluid resuscitation: a systematic review.
AB  - OBJECTIVE: To systematically review the effects of isotonic crystalloids compared
      with colloids in fluid resuscitation. DATA SOURCES: Computerized bibliographic
      search of published research and citation review of relevant articles. STUDY
      SELECTION: All randomized clinical trials of adult patients requiring fluid
      resuscitation comparing isotonic crystalloids vs. colloids were included.
      Pulmonary edema, mortality, and length of stay were evaluated. Independent review
      of 105 articles identified 17 relevant primary studies of 814 patients. Weighted
      c about article inclusion was high (0.76). DATA EXTRACTION: Data on population,
      interventions, outcomes, and methodologic quality of the studies were obtained by
      duplicate independent review with differences resolved by consensus. Weighted ic
      on the validity assessment was moderate (0.54). DATA SYNTHESIS: No difference was
      observed overall between crystalloid and colloid resuscitation with respect to
      mortality and pulmonary edema; however, the power of the aggregated data was
      insufficient to detect small but potentially clinically important differences.
      Subgroup analysis suggested a statistically significant difference in mortality
      in trauma in favor of crystalloid resuscitation (relative risk 0.39, 95%
      confidence intervals: 0.17 to 0.89). Several methodologic issues are noteworthy
      regarding the primary studies, including lack of blinding (except in three
      studies). The type, dose, and duration of fluid administration and outcomes
      measured were different across these trials. CONCLUSIONS: Overall, there is no
      apparent difference in pulmonary edema, mortality, or length of stay between
      isotonic crystalloid and colloid resuscitation. Crystalloid resuscitation is
      associated with a lower mortality in trauma patients. Methodologic limitations
      preclude any evidence-based clinical recommendations. Larger well-designed
      randomized trials are needed to achieve sufficient power to detect potentially
      small differences in treatment effects if they truly exist.

PMID- 9934918
TI  - Hearing loss in critical care: an unappreciated phenomenon.
AB  - OBJECTIVES: The objectives of this article are to review the physiology of
      hearing; identify acute pathologic and perceived causes of hearing loss in the
      adult critically ill patient; and to discuss its evaluation, treatment, and
      prevention. DATA SOURCES: Computerized bibliographic search of MEDLINE from 1966
      to the present of all relevant articles in all languages on acute hearing loss in
      the adult population. DATA EXTRACTION: Data gathered from studies and reports of
      acute hearing loss as relates or potentially relates to the peri-intensive care
      unit (ICU) period. DATA SYNTHESIS: Hearing loss is an infrequent but potentially
      serious complication associated with critical illness. The causes of hearing loss
      in the ICU patient include mechanical or accidental trauma, administration of
      ototoxic medications, local or systemic infections, vascular and hematologic
      disorders, autoimmune diseases, and environmental noise. Patients who are
      elderly, have coexisting liver or renal failure, or who are receiving
      concomitantly administered ototoxic drugs are particularly at risk for developing
      hearing loss. A thorough assessment of potential causes of hearing loss and
      audiological examination should be undertaken on all ICU patients suspected of
      hearing loss. Mechanical, pharmacologic, and environmental strategies are
      available to decrease the incidence of hearing loss in this patient population.
      CONCLUSIONS: Hearing loss should be recognized as a potential clinical problem by
      intensivists. Its causes should be identified and appropriate evaluation and
      therapy initiated. High risk populations should be identified for preventive
      measures.

PMID- 9934919
TI  - Trace element and vitamin concentrations and losses in critically ill patients
      treated with continuous venovenous hemofiltration.
AB  - OBJECTIVES: To measure the blood concentrations of a number of trace elements and
      vitamins in critically ill patients and examine their elimination by continuous
      venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary
      institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight
      critically ill patients requiring renal replacement therapy, nine patients
      requiring intensive care treatment but not requiring renal replacement therapy,
      and nine healthy controls. INTERVENTIONS: Measurement of trace element and
      vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS:
      Compared with normal volunteers, critically ill patients requiring CVVH had
      significantly lower median blood concentrations of vitamin C, vitamin E,
      selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the
      trace element and vitamin concentrations in blood, nor were there differences
      between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate
      were small or undetectable except for Vitamin C, chromium, and copper. Compared
      with normal volunteers, critically ill patients not requiring CVVH also had
      significantly lower median blood concentrations of vitamin C, vitamin E,
      selenium, and zinc. There were no differences between the two critically ill
      groups. CONCLUSIONS: The clinical significance of the reductions in blood
      concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill
      patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains
      unclear.

PMID- 9934920
TI  - Propofol and hypertriglyceridemia: no problem?

PMID- 9934921
TI  - Dental plaque and nosocomial infection: anaerobes can also be involved.

PMID- 9934922
TI  - Complications and mortality associated with anesthesia in dogs and cats.
AB  - The complications and mortality associated with anesthesia of dogs and cats in a
      university teaching hospital were determined. During one year, 2,556 dogs and 683
      cats were anesthetized by the anesthesia service. Hypotension occurred in 179
      (7%) dogs and 58 (8.5%) cats. Cardiac dysrhythmias occurred in 64 (2.5%) dogs and
      12 (1.8%) cats. Transfusions were required in 31 (1.2%) dogs. Hypercapnea
      occurred in 33 (1.3%) dogs and one (less than 1%) cat. Hypoxemia occurred in 14
      (0.5%) dogs. Anesthetic complications, as defined, occurred in 12.0% of dogs and
      10.5% of cats, while deaths associated with the perianesthetic period occurred in
      0.43% of dogs and 0.43% of cats.

PMID- 9934923
TI  - Traumatic tricuspid insufficiency in a kitten.
AB  - A four-month-old, male, common European kitten developed pleural effusion and
      ascites after falling from a fourth-floor flat. Radiographic, bidimensional
      echocardiography and color-flow Doppler findings were compatible with right-sided
      atrioventricular valve insufficiency. Necropsy confirmed the diagnosis that
      tricuspid insufficiency resulted from the rupture of the chordae tendineae of the
      nonseptal cusp of the valve at the level of the cranial papillary muscle
      insertion in the right ventricle.

PMID- 9934924
TI  - Electrocardiographic and radiographic changes in cats with hyperthyroidism:
      comparison of populations evaluated during 1992-1993 vs. 1979-1982.
AB  - Cardiovascular manifestations of feline hyperthyroidism were compared in two
      populations of cats diagnosed at The Animal Medical Center from 1992 to 1993
      (n=202) and 1979 to 1982 (n = 131). The prevalence of sinus tachycardia and
      increased R-wave voltage in lead II were both lower in the 1993 population
      compared with the 1982 population (p less than 0.001). A low frequency of atrial
      and ventricular arrhythmias and intraventricular conduction abnormalities were
      recorded in both populations. No significant differences between populations were
      recorded in the number of cats with mild, moderate, and severe cardiomegaly seen
      on thoracic radiographs. The percentage of cats in which radiographs were deemed
      clinically necessary based upon history and clinical examination was 25% of the
      1993 population, compared with 63% of the 1982 population. The number of cats
      with radiographic evidence of congestive heart failure was 8% in 1993 compared
      with 20% in 1982, although this difference was not statistically significant. In
      conclusion, the incidence and severity of certain thyrotoxic cardiovascular
      manifestations were reduced in cats diagnosed between 1992 and 1993 compared with
      those diagnosed between 1979 and 1982.

PMID- 9934925
TI  - Cyanosis and congenital methemoglobinemia in a puppy.
AB  - A six-month-old Pomeranian was referred for evaluation of cyanosis. The puppy had
      been cyanotic since it was acquired at six weeks of age, but otherwise appeared
      normal. Diagnostics were aimed at the most common causes (i.e., congenital
      defects in the cardiovascular and respiratory systems) of cyanosis in a juvenile
      animal. No clinically significant abnormalities were detected on evaluation of
      thoracic radiographs, echocardiogram, cardiac color-flow Doppler examination, or
      blood gases. At this point, a dysfunction in hemoglobin was considered as a
      possibility. Methemoglobinemia due to deficiency of methemoglobin reductase
      enzyme was diagnosed based on a specific assay.

PMID- 9934926
TI  - Acute paraplegia in a puppy with hemophilia A.
AB  - A seven-week-old, male chow chow-keeshond cross puppy was presented with acute
      paraplegia and episcleral hemorrhage. An X-linked, hereditary coagulopathy was
      suspected and confirmed by clotting factor analysis and necropsy findings of
      intraspinal hemorrhage. In young, male puppies with acute spinal pain and long
      tract signs, intraspinal hematoma secondary to inherited X-linked coagulation
      factor deficiencies should be considered in the differential diagnosis.

PMID- 9934927
TI  - Anticoagulant rodenticide toxicity in 21 dogs.
AB  - Twenty-three episodes of anticoagulant rodenticide toxicity were found in 21 dogs
      during a retrospective study conducted at The Ohio State University Veterinary
      Teaching Hospital. Dyspnea (57%), lethargy (48%), coughing/hemoptysis (30%), and
      pallor (26%) were the most common presenting complaints. Prolonged activated
      clotting time (ACT), prolonged one-stage prothrombin time (OSPT), and prolonged
      activated partial thromboplastin time (APTT) were present in all dogs that had
      not received any prior therapy. Anemia (83%), thrombocytopenia (61%),
      hypoproteinemia (57%), positive fibrin degradation products (FDPs) (55%, six of
      11 tested), and hyperfibrinogenemia (43%, six of 14 tested) were common
      hematological findings. Treatment included therapy with vitamin K1, blood
      products, and supportive care. The survival rate was 83%.

PMID- 9934928
TI  - Iatrogenic Cushing's syndrome and steroid hepatopathy in a cat.
AB  - The distinguishing clinical features of Cushing's syndrome in the cat include
      very friable skin, a high incidence of diabetes mellitus, and the general absence
      of steroid hepatopathy. This case report describes a nine-year-old, spayed female
      domestic shorthair with triamcinolone-induced Cushing's syndrome. Unique to this
      cat were markedly elevated liver enzymes which prompted an expanded clinical
      evaluation. An ultrasonographic-guided liver biopsy demonstrated diffuse
      hepatocellular vacuolation that stained periodic acid-Schiff (PAS) positive and
      was removed subsequently with diastase application, indicating glycogen
      accumulation. These findings are compatible with the rarely seen syndrome of
      steroid hepatopathy in the cat.

PMID- 9934929
TI  - Duodenal perforation in a cat following the administration of nonsteroidal anti
      inflammatory medication.
AB  - A one-year-old, female domestic shorthair was presented for septic peritonitis 10
      days following a routine ovariohysterectomy and subsequent oral administration of
      carprofen. Exploratory laparotomy revealed a perforated duodenum which was
      treated with a gastroduodenostomy (Billroth I) and open abdomen management.
      Etiology of the duodenal perforation was most likely due to the administration of
      carprofen, a nonsteroidal anti-inflammatory drug approved for oral use in dogs
      only.

PMID- 9934930
TI  - Platelet-associated immunoglobulin (antiplatelet antibody) in canine Rocky
      Mountain spotted fever and ehrlichiosis.
AB  - Antiplatelet antibodies were detected in the sera of dogs with naturally
      occurring and experimentally induced Rickettsia rickettsii and Ehrlichia canis
      infections. This is the first known report documenting elevated platelet
      associated immunoglobulin (PAIg) titers in Rocky Mountain spotted fever (RMSF)
      infections. In the naturally occurring RMSF infections and ehrlichiosis, the
      antibodies persisted for weeks or months, even when the platelet counts had
      normalized. Results of this study indicate an immunological component for
      rickettsial thrombocytopenia. Therefore, current therapeutic recommendations,
      especially regarding avoiding the use of immunosuppressive drugs in patients with
      rickettsial diseases, need to be critically reviewed.

PMID- 9934931
TI  - Idiopathic multifocal osteopathy in four Scottish terriers (1991-1996).
AB  - This case series describes four Scottish terriers with an osteopathic condition,
      characterized by multifocal absence of bone in the skull, cervical spine, and
      proximal radii, ulnae, and femora. All dogs were affected clinically; two dogs
      were euthanized due to progression of the disease, one died acutely, and one was
      euthanized for an oral melanoma. Histopathology in one case was characterized by
      osteoclastic osteolysis and replacement of bone with fibrous tissue. This disease
      has some characteristics of human osteolysis syndromes. Three of the dogs were
      related through pedigree analysis, and the pedigree of the other dog was not
      available. The name, idiopathic multifocal osteopathy, is used to describe a new
      disease in dogs, found particularly in Scottish terriers.

PMID- 9934932
TI  - Correction of malocclusion secondary to maxillary impaction fractures using a
      mandibular symphyseal realignment in eight cats.
AB  - Eight cats with stable impaction fractures of the maxilla, sufficient to cause
      malocclusion, were treated by mandibular symphyseal realignment. The mandibular
      symphyseal realignment allowed occlusion to be restored with a minimal amount of
      dental work (e.g., enameloplasty, endodontics, or tooth extraction) in a majority
      of the cases. Enameloplasties were performed in two cats, one of which had a
      vital pulpotomy. Tooth extractions (range, two to five teeth; mean, 3.3 teeth)
      were performed in four cats. All cats were doing well at the time of in-hospital
      follow-up at one month to four years (mean, 2.1 yrs) postoperatively. Further
      telephone follow-up was obtained, from 1.5 to five years (mean, 3.4 yrs) after
      surgery, from all but one owner, with no change from the in-hospital evaluations.
      All owners contacted were pleased with the long-term outcome.

PMID- 9934935
TI  - Mass units or molar units for drug concentration?

PMID- 9934933
TI  - A proposed new therapeutic protocol for the treatment of canine mange with
      ivermectin.
AB  - Ivermectin was used orally for the treatment of generalized demodicosis or
      scabies in 222 dogs. The dose was increased gradually from 50 microg/kg body
      weight on day one, 100 microg/kg body weight on day two, 150 microg/kg body
      weight on day three, 200 microg/kg body weight on day four, to the final dose of
      300 microg/kg body weight on day five. This dose was continued daily until
      resolution for demodicosis and given four times at seven-day intervals for
      scabies. Two patients developed clinical ivermectin toxicity after two and 10
      days, respectively, and recovered once the drug was discontinued. A gradual
      increase of the ivermectin dose into the therapeutic range and thorough
      monitoring of patients during treatment are recommended when using this drug to
      treat patients with generalized demodicosis or scabies.

PMID- 9934934
TI  - Clinical efficacy of milbemycin oxime in the treatment of nasal mite infection in
      dogs.
AB  - A multicentric clinical trial was done to evaluate the clinical efficacy of
      milbemycin oxime in the treatment of nasal mite (Pneumonyssoides caninum)
      infection in dogs. Milbemycin oxime was given to 70 dogs of different breeds,
      genders, and ages, with clinical signs associated with nasal mite infection.
      Twenty-five dogs had a verified infection, and 45 dogs had signs suggestive of
      nasal mite infection. Milbemycin oxime was given at the dosage of 0.5 to 1.0
      mg/kg body weight orally once a week for three consecutive weeks. One month after
      initiation of treatment, 68 of the dogs had no more clinical signs associated
      with nasal mite infection.

PMID- 9934936
TI  - Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic
      antidepressant.
AB  - Evidence that serotonergic antidepressants are effective for treating
      premenstrual syndrome (PMS) raises the question of whether dosing only in the
      symptomatic premenstrual phase is effective for this disorder. This preliminary
      randomized, double-blind study compared the responses to half-cycle or full-cycle
      dosing of sertraline in 31 patients who completed a preceding double-blind, short
      term treatment trial. The subjects fulfilled criteria for severe PMS when they
      entered the preceding controlled trial. At the end of the short-term treatment
      trial, the double-blind was not broken; both improved and unimproved subjects
      were randomized in a double-blind fashion to receive either full-cycle or half
      cycle sertraline in the 3-month extension study. Results showed that the total
      premenstrual scores from the Penn Daily Symptom Report (DSR) were lower in the
      half-cycle dosing group in each of the 3 treatment months but did not differ with
      statistical significance from the full-cycle dosing group. Further analysis of
      the 17 DSR items showed that mood swings, nervous tension, feeling out of
      control, and confusion were significantly lower (p < 0.05) at endpoint in the
      half-cycle dosing group. Overall, subjects who improved in prior treatment
      remained improved; approximately half the subjects who were unimproved at entry
      into the extension study improved, regardless of the dosing regimen. The results
      add support to other preliminary reports of efficacy of serotonergic
      antidepressants administered premenstrually and indicate the clinical importance
      of determining an optimal dose/benefit ratio of serotonergic antidepressants for
      PMS patients.

PMID- 9934937
TI  - Blood pressure changes during short-term fluoxetine treatment.
AB  - Recent reports of sustained hypertension in some patients receiving venlafaxine
      have rekindled concerns about antidepressant-induced hypertension. This study
      examined sitting and standing systolic and diastolic blood pressure, pulse rate,
      and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40
      +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest
      reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001)
      blood pressure measures were observed in the entire patient sample. Patients with
      pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase
      in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment
      diastolic blood pressure > or = 90 mmHg and < or = 95 mmHg (N = 57) had a modest
      reduction in mean diastolic blood pressure (p < 0.001). Patients with
      preexisting, stable cardiovascular disease (including hypertension) (N = 35)
      showed no significant blood pressure change (p = not significant). Of the
      patients receiving fluoxetine, 1.7% had sustained hypertension for > or = 3
      consecutive clinic visits-a rate significantly lower than that previously
      reported with venlafaxine (4.8%) (chi2 = 13.3, p < 0.001) and similar to that
      previously seen with placebo (2.1%). In conclusion, these data demonstrate a low
      rate of sustained hypertension (1.7%) during short-term fluoxetine treatment.

PMID- 9934938
TI  - An open clinical trial of fluvoxamine treatment of psychogenic excoriation.
AB  - The purpose of this study was to examine the safety and efficacy of fluvoxamine
      in the treatment of psychogenic (neurotic) skin excoriation. Fourteen subjects
      with psychogenic excoriation were given fluvoxamine in a 12-week, open-label
      trial after completion of the Structured Clinical Interview for DSM-IV. All
      subjects met DSM-IV criteria for at least one comorbid psychiatric disorder, with
      mood disorder the most common. Most subjects' excoriation had features of an
      impulse control disorder. Both completers (N = 7) and the entire group had
      significant improvement on the modified Yale-Brown Obsessive Compulsive Scale but
      no improvement on the Hamilton Rating Scale for Depression. In the self-report
      data, the seven completers had significant reduction in behaviors involving the
      skin (e.g., scratching, picking, gouging, or squeezing) and in global assessment
      of symptoms. Endpoint analysis of all 14 subjects' self-report data demonstrated
      significant improvement in the presence of skin sensations, skin appearance and
      lesions, behaviors involving the skin, control over skin behavior, and global
      assessment. The results of this preliminary open trial suggest that fluvoxamine
      may be effective in reducing psychogenic excoriation, and this effect seems to be
      independent of mood. Controlled studies are needed to confirm these findings.

PMID- 9934939
TI  - Testosterone therapy for human immunodeficiency virus-positive men with and
      without hypogonadism.
AB  - This study was designed to evaluate the safety and effectiveness of testosterone
      therapy for clinical symptoms of hypogonadism (low libido, low mood, low energy,
      loss of appetite/weight) in human immunodeficiency virus-positive men with CD4
      cell counts less than 400 cells/mm3 and deficient or low normal serum
      testosterone levels. The trial consisted of 8 weeks of open treatment with 400 mg
      of intramuscular testosterone cypionate biweekly. Responders were maintained at
      this dosage for another 4 weeks and then were randomized in a double-blind,
      placebo-controlled, 6-week discontinuation trial. Of the 112 men who completed at
      least 8 weeks of treatment, 102 (91%) were rated as responders on a global
      assessment of sexual desire/function. Of the 34 study completers with major
      depressive disorder and/or dysthymia, 79% reported significant improvement in
      mood at week 8. Average weight change was a gain of 3.7 pounds, with 45% gaining
      more than 5 pounds. Eighty-four men entered and 77 completed the double-blind
      phase; of these, 78% of completers randomized to testosterone and 13% randomized
      to placebo maintained their response. No significant medical or immunologic
      adverse effects were identified. Testosterone therapy was well tolerated and
      effective in ameliorating symptoms of clinical hypogonadism, and equally so for
      men with and without testosterone deficiency. For patients with major depression
      and/or dysthymia, improvement was equal to that achieved with standard
      antidepressants.

PMID- 9934940
TI  - Beneficial treatment of age-related sleep disturbances with prolonged intranasal
      vasopressin.
AB  - Disturbed sleep is common in the elderly and is characterized by disordered sleep
      architecture with reduced time spent in slow wave sleep (SWS) and in rapid eye
      movement (REM) sleep. At present, no treatments are available to fully compensate
      for these disorders. In the elderly, vasopressin content is decreased at various
      brain sites. Investigating the effects of a 3-month intranasal vasopressin
      administration on sleep and cognitive functions in two elderly subjects in a
      foregoing pilot study, the authors found that the most pronounced influence of
      the peptide was a marked increase in SWS. This placebo-controlled, double-blind,
      randomized study examined the influences of a 3-month period of daily intranasal
      vasopressin treatment (20 IU before bedtime and after awakening) on nocturnal
      sleep in 26 healthy elderly subjects (mean age, 74.2 years). Intranasal treatment
      of vasopressin increased (1) the total sleep time, on average, by 45 minutes (p <
      0.002); (2) time spent in SWS by 21 minutes (p < 0.025); and (3) time in REM
      sleep in the second half of the night by 10 minutes (p < 0.01). Vasopressin
      promotes sleep time and improves sleep architecture after prolonged intranasal
      administration in elderly subjects, although scores of subjective sleep quality
      did not change. Results suggest that age-related deterioration of sleep
      architecture can benefit from intranasal treatment with vasopressin. But a
      potential use in clinical settings will also depend on demonstrating improved
      subjective sleep quality, which remained unaffected by vasopressin in this study
      of elderly subjects.

PMID- 9934941
TI  - Olanzapine treatment of children, adolescents, and adults with pervasive
      developmental disorders: an open-label pilot study.
AB  - This pilot study examined the efficacy and tolerability of olanzapine in the
      treatment of children, adolescents, and adults with pervasive developmental
      disorders (PDDs). Eight patients with principal diagnoses (DSM-IV) of autistic
      disorder (N = 5) or PDD not otherwise specified (N = 3) were given olanzapine in
      an open-label, prospective fashion for 12 weeks. Clinical ratings were obtained
      at baseline and at the end of weeks (EOWs) 4, 8, and 12. Seven of eight patients
      completed the 12-week trial, and six of the completers were deemed clinical
      responders as measured by ratings at the EOW 12 of "much improved" or "very much
      improved" on the global improvement item of the Clinical Global Impression Scale.
      Significant improvements in overall symptoms of autism, motor restlessness or
      hyperactivity, social relatedness, affectual reactions, sensory responses,
      language usage, self-injurious behavior, aggression, irritability or anger,
      anxiety, and depression were observed. Significant changes in repetitive
      behaviors were not observed for the group. The EOW 12 mean +/- SD daily dose of
      olanzapine was 7.8 +/- 4.7 mg/day. The drug was well tolerated with the most
      significant adverse effects noted to be increased appetite and weight gain in six
      patients and sedation in three. With respect to weight gain, the mean +/- SD
      weight for the group increased from 137.50 +/- 55.81 pounds (62.50 +/- 25.37
      kilograms) at baseline to 155.94 +/- 55.13 pounds (70.88 +/- 25.06 kilograms) at
      EOW 12. No evidence of extrapyramidal side effects or liver function
      abnormalities was seen. These preliminary results suggest that olanzapine may be
      an effective and well tolerated drug in targeting core and related symptoms of
      PDDs in children, adolescents, and adults. Further studies, particularly those
      that are placebo-controlled and double-blinded, are indicated to better define
      the clinical use of olanzapine in these patient populations.

PMID- 9934942
TI  - Characteristics and risk factors of acute dystonia in schizophrenic patients
      treated with nemonapride, a selective dopamine antagonist.
AB  - The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic
      patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a
      selective dopamine antagonist, and the relationship of acute dystonia with
      characteristics of patients and plasma concentrations of the drug and prolactin
      was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the
      onsets of which occurred within 3 days after the initiation of treatment in 90%
      of dystonic patients. The incidence of acute dystonia was significantly higher in
      male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients
      (< or = 30 years) especially had an extremely high incidence of this side effect
      (91.7%). A positive correlation between prolactin response after 1 week of
      treatment and dystonia rating scores was found in male (Spearman rank
      correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p =
      not significant). These results suggest that young male patients have the highest
      risk of neuroleptic-induced dystonia. Prolactin response after 1 week of
      treatment as an index of dopamine blockade may reflect vulnerability to the
      development of acute dystonia at least in male patients treated with nemonapride.

PMID- 9934943
TI  - Treatment attrition among alcohol-dependent men: is it related to novelty seeking
      personality traits?
AB  - "Dropouts" are a major concern when monitoring treatment efficacy in clinical
      trials. Alcohol-dependent patients are especially prone to discontinuing
      treatment, perhaps because of impulsive behavior. The Tridimensional Personality
      Questionnaire (TPQ) measures a trait-like quality, novelty seeking, which may
      reflect impulsiveness. We tested the hypotheses that higher TPQ Novelty Seeking
      subscale scores would be associated with increased rates of treatment dropout and
      increased risk for dropping out earlier. A total of 170 alcohol-dependent men who
      participated in a double-blind, placebo-controlled pharmacotherapeutic trial for
      decreasing relapse drinking completed the TPQ and were monitored until treatment
      dropout. Logistic regression and Cox proportional hazards models were used to (1)
      describe the relationship between the TPQ Novelty Seeking score and the
      dichotomous outcome variable, treatment dropout; and (2) assess the effects of a
      number of potential confounding covariates on the relationship between the risk
      factor, novelty seeking, and the time to the outcome event. The mean Novelty
      Seeking score was significantly higher among study dropouts compared with
      nondropouts (p = 0.003). Higher Novelty Seeking scores were associated with a
      higher adjusted odds ratio for dropping out (adjusted odds ratio = 1.07, 95%
      confidence interval [CI] = 1.00-1.15) and a higher adjusted hazard rate for
      dropping out earlier (adjusted hazard rate = 1.05, 95% CI = 1.00-1.09). The TPQ
      Novelty Seeking subscale score may identify a subgroup of alcohol-dependent men
      who are at risk for dropping out of treatment. This information may be useful for
      developing treatment plans to encourage these high-risk patients to remain in
      treatment.

PMID- 9934944
TI  - Prolactin levels and adverse events in patients treated with risperidone.
AB  - Hyperprolactinemia is a common clinical disorder that may lead to sexual
      dysfunction or galactorrhea. It may arise from a variety of etiologies, including
      the use of antipsychotic agents, presumably because of a dopamine receptor
      blockade. This analysis was designed to characterize the relationship between
      risperidone, serum prolactin levels, and possible clinical sequelae. All data
      from randomized, double-blind studies of risperidone in patients with chronic
      schizophrenia were analyzed. The two largest studies (the North American and
      multinational trials) included 841 patients (259 women, 582 men) with paired
      prolactin level data and 1,884 patients (554 women, 1,330 men) with data on six
      adverse events possibly associated with increased prolactin levels (amenorrhea,
      galactorrhea, and decreased libido in women; erectile dysfunction, ejaculatory
      dysfunction, gynecomastia, and decreased libido in men). Both risperidone and
      haloperidol produced dose-related increases in plasma prolactin levels in men and
      women. Among women, the risperidone dose was not correlated with adverse events,
      nor were the adverse events correlated with endpoint prolactin levels. Among men,
      the incidence of adverse events was positively correlated with risperidone dose;
      however, at risperidone doses of 4 to 10 mg/day the incidence of adverse events
      was not significantly higher than that observed in patients receiving placebo.
      Furthermore, adverse events in men were unrelated to plasma prolactin levels.
      Risperidone-associated increase in serum prolactin levels was not significantly
      correlated to the emergence of possible prolactin-related side effects.

PMID- 9934945
TI  - An open trial of olanzapine in patients with treatment-refractory psychoses.
AB  - Olanzapine's structural similarities to clozapine and the results of premarketing
      clinical trials suggested potential usefulness in treating patients with
      treatment-refractory psychoses. Sixteen inpatients from the state hospital with
      severe, refractory schizophrenic or schizoaffective psychoses received olanzapine
      in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day
      for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and
      other antipsychotic agents were discontinued before olanzapine was started.
      Patients frequently became more agitated within the first several weeks of
      initiating treatment, requiring the increased use of benzodiazepines and often
      leading to the discontinuation of olanzapine. Two patients improved
      significantly. Overall, significant clinical improvement was noted only for motor
      side effects. This study concluded that olanzapine was not effective in this
      heterogeneous group with chronic, severe, treatment-resistant psychosis when used
      in this manner. Further research is needed to explain the tendency toward
      agitation upon transition to olanzapine, which is reminiscent of reported
      risperidone complications. Clinicians should be alert for this complication and
      should minimize concomitant medication changes that might add to the risk of
      emergent agitation.

PMID- 9934947
TI  - Buspirone: future directions.
AB  - The Food and Drug Administration approved the use of buspirone for generalized
      anxiety disorder (GAD) in 1986. Since then, numerous studies have examined the
      efficacy and safety of buspirone for patients with not only generalized feelings
      of anxiety, but also panic disorder, major depressive disorder, obsessive
      compulsive disorder, body dysmorphic disorder, social phobia, posttraumatic
      stress disorder, selective serotonin reuptake inhibitor-induced adverse events,
      dementia, behavioral disturbances, attention deficit-hyperactivity disorder, and
      tobacco dependency. Although relatively few placebo-controlled trials have been
      conducted on patients with problems other than GAD, an ever-growing body of
      research suggests future directions for the use of buspirone. This article
      reviews the body of research relating to new uses for buspirone.

PMID- 9934946
TI  - Effects of SSRIs on sexual function: a critical review.
AB  - Sexual problems are highly prevalent in both men and women and are affected by,
      among other factors, mood state, interpersonal functioning, and psychotropic
      medications. The incidence of antidepressant-induced sexual dysfunction is
      difficult to estimate because of the potentially confounding effects of the
      illness itself, social and interpersonal comorbidities, medication effects, and
      design and assessment problems in most studies. Estimates of sexual dysfunction
      vary from a small percentage to more than 80%. This article reviews current
      evidence regarding sexual side effects of selective serotonin reuptake inhibitors
      (SSRIs). Among the sexual side effects most commonly associated with SSRIs are
      delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and
      arousal difficulties are also frequently reported, although the specific
      association of these disorders to SSRI use has not been consistently shown. The
      effects of SSRIs on sexual functioning seem strongly dose-related and may vary
      among the group according to serotonin and dopamine reuptake mechanisms,
      induction of prolactin release, anticholinergic effects, inhibition of nitric
      oxide synthetase, and propensity for accumulation over time. A variety of
      strategies have been reported in the management of SSRI-induced sexual
      dysfunction, including waiting for tolerance to develop, dosage reduction, drug
      holidays, substitution of another antidepressant drug, and various augmentation
      strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and alpha2 adrenergic
      receptor antagonists, 5-HT1A and dopamine receptor agonists, and
      phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should
      not be viewed as entirely negative; some studies have shown improved control of
      premature ejaculation in men. The impacts of sexual side effects of SSRIs on
      treatment compliance and on patients' quality of life are important clinical
      considerations.

PMID- 9934949
TI  - Ketoprofen intoxication delirium.

PMID- 9934948
TI  - Possible gabapentin-induced thyroiditis.

PMID- 9934950
TI  - Venlafaxine-fluoxetine interaction.

PMID- 9934951
TI  - Dystonia associated with sertraline.

PMID- 9934952
TI  - Olanzapine in the treatment of tardive dyskinesia: a report of two cases.

PMID- 9934953
TI  - Effectiveness of risperidone in Huntington chorea patients.

PMID- 9934954
TI  - Development and infectivity of eggs and larvae derived from pigs trickle-infected
      with Oesophagostomum dentatum at different dose levels.
AB  - We examined the impact of different Oesophagostomum dentatum dose levels and
      durations of infection on the development and infectivity of the following
      generation. Pigs were trickle-infected with 200, 2,000 or 20,000 L3/week over 20
      weeks. Egg hatch assays were performed at monthly intervals; however, no
      consistent differences were found between any of the dose groups in the
      development of eggs into first-stage larvae. To compare larval infectivity,
      larvae were derived from faecal cultures set up from the low- and the high-dose
      groups in the early and the late part of the experiment, and were inoculated into
      helminth-free pigs (5,000 L3/pig). Worm establishments were significantly higher
      (P<0.05) in the group of pigs receiving larvae derived early in the experiment
      from the low-dose group compared with the two groups receiving larvae from high
      dose groups, thus indicating an adverse effect of high doses of trickle infection
      on the later infectivity of L3 larvae derived from excreted eggs.

PMID- 9934955
TI  - Formation of calcareous corpuscles in the lumen of excretory canals of Taenia
      solium cysticerci.
AB  - Platyhelminths, like many other organisms, are capable of producing mineral
      concretions. In cestodes these are referred to as calcareous corpuscles. Studies
      on these concretions in different cestodes both in vivo and in vitro have
      resulted in a number of hypotheses on their origin, formation, and structure.
      Calcareous corpuscles are believed to be of cellular origin, although the kind of
      cell involved and the mechanisms of mineralization remain under discussion. In
      the present paper we show that formation of calcareous corpuscles in cysticerci
      of Taenia solium is not of intracellular origin, as described for other cestodes,
      but occurs extracellularly in the lumen of protonephridial ducts in a way similar
      to that proposed for trematodes. This finding enhances the function of the
      protonephridial ducts, at least in the larvae of T. solium, to the roles formerly
      ascribed to the calcareous corpuscles.

PMID- 9934956
TI  - Soluble-protein and antigenic heterogeneity in axenic Blastocystis hominis
      isolates: pathogenic implications.
AB  - The protein profile and the antigenic cross-reactivity of 18 axenic isolates of
      Blastocystis hominis obtained from symptomatic patients with chronic diarrhea (14
      isolates) showing no evidence of parasitic etiology and from patients with acute
      diarrhea attributable in 2 cases to Salmonella spp. were analyzed. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of soluble proteins showed the
      existence of a common profile composed of 31 bands, with molecular weights
      ranging between 24 and >200 kDa, and minor differences in the proteins of 149,
      118, 106, 50, 48, 47, and 30 kDa. These differences allowed us to classify the
      strains into three related patterns (I-III). In an indirect immunofluorescence
      assay, all strains were serologically identical, but two related antigenic groups
      (1 and 2) were found in double-immunodiffusion and Western-blot studies. The
      isolates of protein patterns I and II belonging to antigenic group 1 were
      isolated from patients with chronic diarrhea, whereas the four isolates from
      patients with acute diarrhea were clustered in protein pattern III and in
      antigenic group 2. These results confirm the protein and antigenic heterogeneity
      of B. hominis and the existence of demes with different pathogenic roles.

PMID- 9934957
TI  - Immunological evaluation of a 26-kDa antigen from Taenia solium larvae for
      specific immunodiagnosis of human neurocysticercosis.
AB  - Human neurocysticercosis, due to infection of the central nervous system by
      cysticerci of Taenia solium, is a severe form of neurologic disease occurring in
      Central and South America. Specific proteins from scolex antigen from cysticerci
      were purified by polyacrylamide gel electrophoresis and electroelution and
      recognized in Western blots by antibodies present in sera from patients with
      neurocysticercosis. The proteins appeared as 13-, 17-, and 26-kDa bands on
      Coomassie blue-stained gels and proved to be specific to cysticerci of T. solium.
      No cross-reactivity with sera from patients with taeniasis or hydatidosis was
      observed. Enzyme-linked immunosorbent assay using the purified proteins of 13,
      17, and 26 kDa demonstrated rates of 53%, 88%, and 100% specificity,
      respectively, at the cutoff serum dilution of 1:32 for the specific
      immunodiagnosis of human neurocysticercosis.

PMID- 9934958
TI  - Development of Blastocystis hominis cysts into vacuolar forms in vitro.
AB  - The development of cysts of Blastocystis hominis isolated from human feces by the
      Ficoll-Paque concentration method and cultured in Jones' medium containing 10%
      horse serum is described. The morphological changes were studied by light and
      transmission electron microscopy at different intervals for up to 48 h. The cysts
      developed into a large number of vacuolar forms within 24 h, and binary fission
      was the only mode of reproduction observed.

PMID- 9934959
TI  - A survey of Blastocystis in domestic chickens.
AB  - The prevalence and morphology of Blastocystis in fresh faecal material from 227
      domestic chickens was investigated. A very high prevalence of infection
      (approximately 95%) was found in chickens from four of the five commercial farms
      studied. Extremely high numbers of Blastocystis were found in the majority of
      samples. Blastocystis cells showed considerable variation in size, ranging from
      approx. 3 microm to approx. 120 microm in diameter. This size range is more
      extreme than those previously recognised for the organism from chickens. All
      chickens from one farm appeared free of Blastocystis infection. Most Blastocystis
      cells appeared to be the vacuolar form, although the shape of the cells and the
      appearance of the central vacuole contents varied considerably within and among
      faecal samples. Nuclei showed "spots" of electron-opaque material, generally
      arranged as a band within the nuclei. Multiple individual cysts within a single
      outer fibrillar layer were found in addition to single cysts without an
      encompassing fibrillar layer.

PMID- 9934960
TI  - Flow cytometry analysis of drug transport mechanisms in Haemonchus contortus
      susceptible or resistant to anthelmintics.
AB  - The role of membrane drug-transport mechanisms in resistance to anthelmintics was
      examined using a flow cytometry method. This method was adapted from assays
      developed for the study of similar mechanisms in tumor cells. Rhodamine 123, a P
      glycoprotein transport probe, associated with the reversal agent verapamil gave a
      significantly higher level of green fluorescence in Haemonchus contortus
      resistant eggs as compared with that of susceptible eggs. In the same way,
      verapamilbodipy, a new fluorescent probe for the detection of multidrug
      resistance in cells, showed a significantly higher degree of binding to resistant
      eggs. The results confirm those obtained with biological drug assays using both
      anthelmintics and verapamil and provide a quantitative and effective methodology
      for the functional study of multidrug resistance in nematodes.

PMID- 9934961
TI  - Tegumental topography of the plerocercoid of Gymnorhynchus gigas (Cestoda :
      Trypanorhyncha).
AB  - The tegumental topography of the plerocercoid of Gymnorhynchus gigas is described
      for the first time. The surface features were examined by scanning electron
      microscopy. Eight different types of microthrix pattern were found. Differences
      in the shape and density of microtriches depend on their location. A unique
      morphological feature is reported herein, namely, filamentous microtriches that
      were arranged in clusters with a dome-shaped pattern when the bothridial surface
      was relaxed but sunk into a crater when the bothridial surface was contracted. In
      contrast to other trypanorhynchan cestodes, palmate microtriches are not found on
      the tegument of this plerocercoid. The microtriches on the caudal extension
      gradually increased in length with growing distance from the blastocyst, which
      showed short knob-like structures. These structures developed into elongated
      filiform microtriches on the posterior region of the caudal extension.

PMID- 9934962
TI  - Strain differences in Blastocystis isolates as detected by a single set of
      polymerase chain reaction primers.
AB  - A total of 20 isolates of Blastocystis were characterized using a single set of
      polymerase chain reaction (PCR) primers. The amplification product revealed five
      types of pattern. All four isolates from Singapore yielded PCR products quite
      different from those of the local isolates. However, most of the local isolates
      showed a major product at either 280 or 500 bp, or both. We also suspected that
      the amplification product detected at 280 bp might be an indicator of the
      pathogenicity of this parasite. One isolate (M12) obtained from a monkey showed
      patterns similar to those of human isolates (10203 and KP1) and probably belongs
      to the same strain. The results indicate that the intraspecific or interstrain
      variations in these 20 Blastocystis isolates belong to 5 different patterns. The
      differences among isolates of the same strain revealed by the presence or absence
      of certain amplification products showed further intrastrain variations in this
      parasite.

PMID- 9934963
TI  - Th1-type cytokines improve resistance to murine cysticercosis caused by Taenia
      crassiceps.
AB  - Resistance and susceptibility to different parasitic diseases have been
      associated with the predominance of Th1- or Th2-type immune responses. In
      experimental murine cysticercosis a Th1 response seems to be involved in
      resistance, whereas Th2 activity is associated with heavy parasite intensities.
      To test this notion the roles of Th1- and Th2-type cytokines in infected mice
      were studied after treatment with anticytokine monoclonal antibodies or with
      recombinant murine cytokines during early stages of infection. Mice receiving
      anti-interleukin 10 (IL-10) carried lower parasite intensities than did control
      mice and developed a strong Th1-type response, whereas mice receiving anti
      interferon gamma (IFN-gamma) showed a dramatic increase in susceptibility.
      Treatment with recombinant cytokines confirmed these results; mice receiving IFN
      gamma and IL-2 showed low parasite numbers, whereas IL-10 induced a significant
      increase in parasite loads. Thus, the Th1-type immune response plays a
      fundamental role in protection against Taenia crassiceps cysticercosis, whereas
      Th2, at least through IL-10, favors parasite establishment.

PMID- 9934964
TI  - Liver fluke (Opisthorchiidae) findings in red foxes (Vulpes vulpes) in the
      eastern part of the Federal State Brandenburg, Germany--a contribution to the
      epidemiology of opisthorchiidosis.
AB  - Parasitological examination of 677 livers from red foxes shot in connection with
      a rabies control programme were carried out in the eastern districts of the
      Federal State Brandenburg/Germany in 1996. Of the foxes, 32.5% were positive for
      opisthorchiid flukes. Metorchis bilis, the most frequently occurring fluke was
      found in 28.1% of foxes with numbers between 1 and 185. Opisthorchis felineus was
      found in 6.7% of fox livers. A maximum of 169 specimens was removed from one
      animal. Pseudamphistomum truncatum was present in only 2 foxes. The percentage of
      positive foxes in different districts varied between 15.8 and 43.3%. Significant
      differences in fluke prevalence were found between districts with a high share of
      surface water compared with a district with a low percentage of surface water. No
      sex-dependent differences in opisthorchiid prevalence were established.

PMID- 9934965
TI  - Levels of tumor necrosis factor alpha, gamma interferon, and interleukins 4,6,
      and 10 as determined in mice infected with virulent or attenuated strains of
      Trypanosoma cruzi.
AB  - Inoculation of BALB/c mice with the virulent Tulahuen (TUL) strain of T. cruzi
      was shown to lead to progressive and eventually lethal infections, whereas
      infection with an attenuated strain (TCC) resulted in a hardly noticeable
      experimental disease producing no tissue damage. To determine whether differences
      in such infection outcome are associated with a particular pattern of cytokine
      response, a study was undertaken to investigate the serum levels of TNF-alpha,
      IFN-gamma, IL-4, IL-6, and IL-10 by using an enzyme-linked immunosorbent assay.
      Mice from both infected groups were bled at 5, 9, 15, 22, 30 and 48 days post
      infection (p.i.), with the same interval being applied for obtention of serum
      samples in age-matched uninfected mice, a group that yielded negative results in
      all cases. Infection with the TUL strain of T. cruzi was accompanied by a
      significant increase of TNF-alpha serum concentrations at day 5 p.i., and
      detectable amounts of IFN-gamma by day 15 p.i., which were exclusively recorded
      in this group. Serum IL-4 was mostly present in TCC mice with values at day 15 pi
      being statistically significant in relation to TUL-infected mice. IL-10 was
      firstly detected at 3 weeks after infection, and showed higher levels in the TCC
      group, although comparisons with TUL-infected group were not significant. At our
      limit of detection, no samples were found to contain IL-6 serum concentrations.
      Infection with virulent parasites seems to be associated with presence of Th1
      type cytokines, whereas challenge with the attenuated TCC strain appears as being
      related to a Th2-type profile.

PMID- 9934966
TI  - Improvements in the infectivity of cryopreserved third-stage larvae of
      Angiostrongylus cantonensis using a programmable freezer.
AB  - Although there have been some advances in the cryopreservation of Angiostrongylus
      cantonensis, the degrees of viability and infectivity of the cryopreserved
      developmental stages have not been high. A two-step freezing protocol using a
      programmable freezer was determined to be effective in improving the infectivity
      of the cryopreserved third-stage larvae of this parasite. After washing steps and
      suspension in 10% (v/v) dimethylsulfoxide and equilibrium at room temperature the
      larvae were placed into the freezer. The temperature was lowered first at 0.8
      degrees C/min from room temperature to -40 degrees C and then at 10 degrees C/min
      to -70 degrees C. The samples were plunged into liquid nitrogen. After storage in
      liquid nitrogen for 7-15 days the larvae were thawed rapidly in 37 degrees C
      water and 27.6% were found to show vigorous "S-shape" movement without
      significant changes in appearance. These larvae (50/rodent) could develop to the
      fifth stage in mice (42.6%) and establish patent infection in rats (40.4%).
      Moreover, there was no significant difference in the recovery rates of
      cryopreserved worms and their unfrozen counterparts. These findings indicate that
      steady precooling conditions may decrease damage with regard to the infectivity
      of cryptopreserved third-stage larvae of A. cantonensis.

PMID- 9934967
TI  - Effects of snail-conditioned water from Biomphalaria glabrata on hatching of
      Echinostoma caproni miracidia.
AB  - In vitro studies were done on Echinostoma caproni eggs with fully developed
      miracidia to determine the effects of snail-conditioned water (SCW) from
      Biomphalaria glabrata on miracidial hatching in the light. Observations were made
      on miracidial hatching at 4, 8, 12, 16, 20, and 24 h in multiwell chambers in the
      presence of SCW (experimentals) versus controls in artificial spring water (ASW).
      The number of hatched eggs was significantly greater (Student's t-test, P<0.05)
      in SCW at all times as compared with those maintained in ASW. Significantly
      greater hatching was also obtained when snails were maintained in intact or
      perforated dialysis sacs in multiwell chambers as compared with sacs without
      snails. Agar plugs impregnated with SCW or the hydrophilic fraction of SCW that
      had been extracted in chloroform-methanol (2:1) did not influence significant
      hatching. However, the lipophilic fraction of the SCW extract caused significant
      hatching. Substances in SCW significantly increase hatching of E. caproni
      miracidia, but details on what these compounds are remain obscure.

PMID- 9934968
TI  - In vitro development of histotropic larvae of Oesophagostomum dentatum under
      various conditions of cultivation.
AB  - We performed a total of 14 trials to evaluate the culture conditions suited best
      for the in vitro production of fourth-stage larvae (L4) of Oesophagostomum
      dentatum. Chicken embryo extract was shown to be redundant, whereas pig blood
      serum, trypticase, liver extract, and yeast extract proved to be important medium
      ingredients. Development to L4 could be moderately accelerated by increases of
      temperature (40 degrees C) and of CO2 concentration (20% in air), but the total
      yield of L4 could not be improved. Thus, conditions of 38.5 degrees C and 10% CO2
      are recommended for routine application.

PMID- 9934969
TI  - Irregular shedding of Blastocystis hominis.
AB  - The shedding pattern of the protozoan parasite, Blastocystis hominis, is
      investigated in man and in experimental animal infections. The shedding pattern
      of the vacuolar and cystic forms of Blastocystis hominis in infected individuals
      have been shown in the present study to be irregular. The study shows that there
      is marked fluctuation in the shedding of the parasite from day to day, varying
      from as high as 17 to 0 per x40 microscopic field. The cystic stages when
      estimated in 8 Blastocystis-infected individuals ranged from as high as 7.4x10(5)
      cysts per gram of stool to 0. The shedding of cystic and vacuolar forms observed
      over a period of 20 days in experimentally-infected Wistar rats were not only
      shown to be irregular but the amount varied from host to host. The study has
      important diagnostic implications in that the stool samples must be collected
      more than once from patients showing clinical signs and symptoms to eliminate the
      cause of it to Blastocystis. The study also shows that there are asymptomatic
      individuals who pass a large amount of cysts as such individuals should be
      treated to prevent transmission to others.

PMID- 9934970
TI  - Recommendations for management of liver and biliary tract disease in cystic
      fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group.

PMID- 9934971
TI  - 1p microdeletion in sibs with minimal phenotypic manifestations.
AB  - We report on two sibs with a paracentric inversion of chromosome 1
      [inv(1)(p22.3p34.1)] and a small deletion of the same chromosome (p34.1-->p34.3).
      They presented with learning disabilities and disturbed conduct but lacked the
      more severe manifestations usually associated with autosomal chromosome deletion.
      Born to an alcoholic mother and later placed in foster care because of abuse and
      neglect, the behavior abnormalities they present are likely to be associated with
      their traumatic postnatal experience. Microscopic deletions without significant
      morphological phenotypic expression have been described but are rarely reported.
      Most reported cases of interstitial deletion of 1p had associated malformations
      and psychomotor retardation. These sibs may represent the first evidence that
      deletion of 1p34.1-->1p34.3 may have little impact on the phenotype.

PMID- 9934972
TI  - Carey-Fineman-Ziter (CFZ) syndrome: report on affected sibs.
AB  - We describe a sib pair with craniofacial anomalies, micrognathia, Mobius
      sequence, generalised myopathy, relative macrocephaly, and developmental delay.
      They appear to have the Carey-Fineman-Ziter syndrome (MIM 254940), which has been
      reported in only four children, a sib pair and two sporadic cases. This report on
      an additional affected brother and sister pair supports autosomal inheritance as
      the likely cause. These cases also confirm that scoliosis, talipes equinovarus,
      and a non-specific primary myopathy are important manifestations of Carey-Fineman
      Ziter syndrome.

PMID- 9934973
TI  - Family studies of infantile visceral myopathy: a congenital myopathic pseudo
      obstruction syndrome.
AB  - We conducted family studies of a rare congenital myopathic pseudo-obstruction to
      provide recurrence risks to families of affected children. This infantile
      visceral myopathy (IVM) involves the smooth muscles of the digestive tract and
      frequently the urinary bladder. Family and pregnancy histories from 16 families
      were evaluated to identify possible environmental or genetic components. The
      families were ethnically and geographically diverse within the United States.
      Eleven of the children were alive, four had died, and the status of one was
      unknown. The sex ratio was 5 females to 11 males. The pregnancy histories
      provided no evidence of a teratogenic cause. In one family, the disorder passed
      from parent to child. There were no consanguineous matings, no similarly affected
      sibs, and except for one case, the family histories did not suggest affected
      relatives. We suspect a new dominant mutation may be responsible for some cases
      of IVM, whereas in others, IVM may be caused from a dominant gene with variable
      expressivity and incomplete penetrance. Therefore, we predict the recurrence risk
      of severely affected children is much less than the 25 or 50% risk sometimes
      given families based on the assumption of autosomal recessive or autosomal
      dominant inheritance. When counseling IVM families, a thorough family history is
      essential. Subsequent pregnancies should be monitored by ultrasound for
      megacystis that was detected prenatally in seven of these cases.

PMID- 9934974
TI  - Behavior and emotional disturbance in Prader-Willi syndrome.
AB  - To determine if persons with the Prader-Willi syndrome (PWS) have increased
      psychopathology when compared with matched controls, and whether there is a
      specific behavior phenotype in PWS, the behavior of 46 persons with PWS was
      compared with that of control individuals derived from a community sample (N =
      454) of persons with mental retardation (MR). Behaviors were studied using the
      Developmental Behaviour Checklist, an instrument of established validity in the
      evaluation of behavioral disturbance in individuals with MR. PWS subjects were
      found to be more behaviorally disturbed than controls overall, and especially in
      antisocial behavior. In addition, some individual behaviors were more common in
      PWS subjects than controls. When these behaviors are considered together with
      findings from other studies using acceptably rigorous methods, a consensus
      behavior phenotype for PWS can be formulated. This will provide a valid
      foundation for studies of the mechanism of genetic pathogenesis of behavior in
      PWS.

PMID- 9934975
TI  - Trisomy 16q in a female newborn with a de novo X;16 translocation and hypoplastic
      left heart.
AB  - We report a case of a newborn female with minor dysmorphic features and
      hypoplastic left heart. Chromosome studies showed that she was the carrier of an
      unbalanced translocation between the X-chromosome and chromosome 16, resulting in
      monosomy for Xp and trisomy for 16q. Only a handful of partial trisomy 16q cases
      have been reported in the literature among liveborns. The great majority of these
      cases have had significant anomalies in contrast to what has been seen in our
      patient. The absence of dysmorphic features and other significant abnormalities
      in this case (with the exception to the hypoplastic left heart), suggested that
      the inactivation of the derivative X chromosome might have played a role in the
      mild phenotype of this patient. Conventional cytogenetic studies were conducted
      in this patient in conjunction with fluorescent in situ hybridization studies,
      which were used to characterize the X inactivation pattern. The studies revealed
      that the X chromosome material in the derivative chromosome was inactive while
      the chromosome 16 derived material in the derivative chromosome was early
      replicating and active in all cells studied.

PMID- 9934976
TI  - Different mutations in the same codon of the proteolipid protein gene, PLP, may
      help in correlating genotype with phenotype in Pelizaeus-Merzbacher disease/X
      linked spastic paraplegia (PMD/SPG2).
AB  - Pelizaeus-Merzbacher disease/X-linked spastic paraplegia (PMD/SPG2) comprises a
      spectrum of diseases that range from severe to quite mild. The reasons for the
      variation in severity are not obvious, but suggested explanations include the
      extent of disruption of the transmembrane portion of the proteolipid protein
      caused by certain amino acid substitutions and interference with the trafficking
      of the PLP molecule in oligodendrocytes. Four codons in which substitution of
      more than one amino acid has occurred are available for examination of clinical
      and potential structural manifestations: Valine165 to either glutamate or
      glycine, leucine 045 to either proline or arginine, aspartate 202 to asparagine
      or histidine, and leucine 223 to isoleucine or proline. Three of these mutations,
      Val165Gly, Leu045Pro, and Leu223Ile have not been described previously in humans.
      The altered amino acids appear in the A-B loop, C helix, and C-D loop,
      respectively. We describe clinically patients with the mutations T494G
      (Val165Gly), T134C (Leu045Pro), and C667A (Leu223Ile). We discuss also the
      previously reported mutations Asp202Asn and Asp202His. We have calculated the
      changes in hydrophobicity of short sequences surrounding some of these amino
      acids and compared the probable results of the changes in transmembrane structure
      of the proteolipid protein for the various mutations with the clinical data
      available on the patients. While the Val165Glu mutation, which is expected to
      produce disruption of a transmembrane loop of the protein, produces more severe
      disease than does Val165Gly, no particular correlation with hydrophobicity is
      found for the other mutations. As these are not in transmembrane domains, other
      factors such as intracellular transport or interaction between protein chains
      during myelin formation are probably at work.

PMID- 9934977
TI  - Ectopic bronchus: an insufficiently recognized malformation causing respiratory
      morbidity in VATER association.
AB  - An 11-month-old boy presented with recurrent wheezing and atelectasis in the
      right upper lobe of the lung. Bronchoscopy and bronchography confirmed an ectopic
      bronchus arising from the right main bronchus. The diagnosis of VATER association
      was made on the basis of multiple vertebral and rib anomalies, imperforate anus
      with a perineal fistula, unilateral hydronephrosis, atrial septal defect, and a
      preauricular tag, he did not have tracheo-esophageal fistula. We emphasize the
      importance of recognizing tracheobronchial anomalies in VATER association.

PMID- 9934978
TI  - Molecular cytogenetic analysis of a de novo 5q31q33 deletion associated multiple
      congenital anomalies: case report.
AB  - Interstitial deletions are relatively rare chromosomal anomalies that usually
      arise de novo. The data describing the phenotype associated with interstitial
      deletions of 5q are very limited. We describe the first case of multiple fetal
      anomalies, diagnosed on prenatal sonographic examination, associated with a
      deletion at 5q31q33. Sonographic examination at 23 weeks' gestation demonstrated
      growth parameters consistent with 20 weeks' gestation; a 7-mm nuchal fold; a
      dilated loop of bowel adjacent to the stomach suggestive of duodenal atresia;
      clubbing of the left foot; a narrow aorta; suspected ventricular septal defect;
      and placental thickening. The patient delivered a severely growth-restricted
      fetus and enlarged placenta at 30 weeks' gestation. The infant died neonatally.

PMID- 9934979
TI  - Persistent truncus arteriosus in monozygotic twins: case report and literature
      review.
AB  - We report on a pair of monozygotic twins with persistent truncus arteriosus. They
      had no evident clinical signs of DiGeorge syndrome. Pathologic examination of the
      placenta and DNA analysis in chromosomes 7, 8, and 15 was consistent with
      monozygosity. Fluorescence in situ hybridization test was negative for chromosome
      22q11 microdeletion. Family history revealed a female cousin with tetralogy of
      Fallot. The isolated presence of this conotruncal abnormality in monozygotic
      twins is extremely rare. The genetic considerations are discussed.

PMID- 9934980
TI  - Frequencies of chromosomal abnormalities at amniocentesis: over 20 years of
      cytogenetic analyses in one laboratory.
AB  - Prenatal diagnosis of chromosomal disorders has been performed for more than 20
      years, mainly for advanced maternal age. Chromosomal abnormality rates derived
      from second trimester amniocentesis have mainly come from a collection of small
      scale studies from North America and Western Europe. Accurate risk estimates for
      chromosomal abnormalities are important tools for the physician or obstetrician
      who would need to make referrals to a prenatal genetic center. This paper
      presents amniocentesis rates of clinically significant cytogenetic abnormalities
      for various indications, including advanced maternal age, previous chromosomal
      abnormality, parental structural rearrangement and a family history of aneuploidy
      as defined in the text. These data come from a Canadian prenatal diagnosis
      laboratory with more than 20 years experience in second trimester cytogenetic
      analysis. They show that the overall frequency of chromosomal abnormalities for
      advanced maternal age (> or = 35 years) is 1.79%. In this group, 21% of all
      abnormalities are structural rearrangements (including markers) and less than
      half of all abnormalities are trisomy 21. The advanced maternal age specific risk
      of aneuploidies at second trimester is 1.24%. Recurrence risk for aneuploidy
      after a previous one is 1.29%. However, it is much higher (4.84%) for women of >
      or = 35 years. When a parent's brother, sister, nephew or niece is affected, the
      risk of occurrence of aneuploidies (0.24%) is not elevated. When there is a
      balanced translocation in one of the parents, the overall risk is 10.2% for
      unbalanced translocations and 37.3% for balanced translocations.

PMID- 9934981
TI  - Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal
      ciliary structure and function, impaired mucociliary clearance, and chronic
      middle ear, sinus, and lung disease. PCD is associated with situs inversus in
      approximately 50% of the patients. One proposed explanation for this relationship
      is that normal ciliary function plays a role in normal organ orientation, whereas
      organ orientation in PCD is a random event because of dysfunctional cilia in
      early embryonic development. Another hypothesis for the association between PCD
      and situs inversus is that mutated genes in PCD not only cause defective cilia,
      but are also linked to the control of organ laterality, such that abnormalities
      in this molecular pathway result in random left-right asymmetry. We report on a
      set of monozygotic twin women with PCD. In both patients, deficiency of the inner
      dynein arms was noted on ciliary ultrastructural analysis, associated with a
      clinical syndrome of bronchiectasis, chronic sinusitis, and middle ear disease.
      One of the twins has situs solitus, the other has situs inversus totalis. DNA
      analysis confirmed that the twins are monozygotic. This is consistent with the
      hypothesis that situs inversus occurring in patients with primary ciliary
      dyskinesia is a random but "complete" event in the fetal development of patients
      with PCD.

PMID- 9934982
TI  - Confirmation of linkage of hereditary partial lipodystrophy to chromosome 1q21
      22.
AB  - Familial lipodystrophy is a genetically heterogeneous set of disorders
      characterized by a total or partial absence of subcutaneous fat, diabetes
      mellitus or impaired glucose tolerance, hyperlipidemia, and hypermetabolism
      [Senior and Gellis, 1964]. One subtype, familial partial lipodystrophy Dunnigan
      (FPLD), is a rare autosomal dominant trait that results in an gradual loss of
      subcutaneous fat in the lower trunk and limbs, Type V hyperlipoproteinemia,
      hypertriglyceridemia, and insulin-resistant diabetes. Previous reports of this
      condition have been limited to case reports or very small families. Recently,
      Peters et al. reported on linkage of five families of Western European descent to
      a 5.3 cM region on chromosome 1q21-22 between the flanking markers D1S305 and
      D1S1600 [Peters et al., 1998: Nat Genet 18:292-295]. We performed linkage and
      haplotype analysis using highly polymorphic, microsatellite markers on a large,
      multigeneration Caucasian kindred of German ancestry. The maximum two-point lod
      score achieved was 4.96 at theta(max) = 0 for marker D1S2721. Multipoint analysis
      gave an overall maximum lod score of 6.27 near marker D1S2721. The results of the
      haplotype analysis support the minimal candidate region as reported by Peters et
      al.

PMID- 9934983
TI  - Sibs diagnosed prenatally with situs inversus totalis, renal and pancreatic
      dysplasia, and cysts: a new syndrome?
AB  - We describe two sib fetuses with situs inversus, cystic dysplastic kidney and
      pancreas, bowing of the lower limbs and clavicles, severe intrauterine growth
      retardation (IUGR), and oligohydramnios. Early prenatal diagnosis of pancreatic
      and dysplastic renal cysts and situs inversus totalis were made in the 18-week
      old fetus. This syndrome differs from that of Ivemark and related syndromes
      because of the presence of situs inversus totalis and absence of hepatic fibrosis
      and cysts. The parents were first cousins, and did not have any cysts of kidney,
      liver, or pancreas detected by ultrasonography.

PMID- 9934984
TI  - TWIST gene mutation in a patient with radial aplasia and craniosynostosis:
      further evidence for heterogeneity of Baller-Gerold syndrome.
AB  - The term Baller-Gerold syndrome was coined by Cohen [1979: Birth Defects 15(5B):
      13-63] to designate the phenotype of craniosynostosis and radial aplasia. It is
      thought to be a rare autosomal recessive condition, which, in some patients,
      presents with additional abnormalities, such as polymicrogyria, mental
      retardation or anal atresia. A phenotypic overlap of Baller-Gerold and Roberts-SC
      phocomelia syndrome was noted when a patient with bicoronal synostosis and
      bilateral radial hypoplasia was found to have premature centromere separation, a
      finding characteristic of Roberts syndrome [Huson et al.,1990: J Med Genet 27:371
      375]. Other cases of presumed Baller-Gerold syndrome were rediagnosed as Fanconi
      pancytopenia, Rothmund-Thomson syndrome or VACTERL association. These reports led
      to a narrowed redefinition of Baller-Gerold syndrome based on the exclusion of
      cytogenetic and hematopoetic abnormalities and the absence of additional
      malformations in patients with craniosynostosis and preaxial upper limb
      abnormalities. Here we report on a patient with unilateral radial aplasia and
      bicoronal synostosis without additional malformations and without chromosome
      breakage, who fits this narrow definition of Baller-Gerold syndrome. We
      identified a novel TWIST gene mutation in this patient, a Glu181Stop mutation
      predicting a premature termination of the protein carboxy-terminal to the helix 2
      domain. This report provides further evidence that Baller-Gerold is of
      heterogeneous cause, and a thorough evaluation is indicated to identify a
      possibly more specific diagnosis, including Saethre-Chotzen syndrome. This
      differential diagnosis is of particular importance, as it is an autosomal
      dominant trait. Therefore, the recurrence risk for parents of an affected child
      can be 50% if one parent carries the mutation, as opposed to the 25% recurrence
      risk for autosomal recessive inheritance. Offspring of the affected patient also
      have a 50% risk to inherit the mutation, while the risk to bear an affected
      offspring for an autosomal recessive trait is very low.

PMID- 9934986
TI  - A dup(17)(p11.2p11.2) detected by fluorescence in situ hybridization in a boy
      with Alport syndrome.
AB  - We describe a de novo dup 17p11 in a boy with Alport syndrome, mild mental
      retardation, and minor anomalies. Combining classical and molecular cytogenetics
      analyses, the karyotype was defined as 46,XY.ish dup
      (17)(p11.2p11.2)(D17S29++,D17S379+). Alport syndrome is associated with mutations
      in the type IV alpha chain collagen gene, however, no known collagen-related gene
      is currently mapped to 17p11. Duplications involving 17p11.2 have been reported
      in Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and in a few sporadic
      patients with mental retardation and minor anomalies, however, no significant
      clinical similarity was found among these cases and the propositus. Further
      studies may clarify the meaning of the association between Alport syndrome and
      duplications of DNA sequences mapped at 17p11.2.

PMID- 9934985
TI  - Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.
AB  - We studied 13 patients with lipoamide dehydrogenase (LAD) deficiency, originating
      from seven Ashkenazi Jewish families. Their disease was characterized by
      recurrent attacks of vomiting, abdominal pain, and encephalopathy accompanied by
      elevated liver transaminases, prolonged prothrombin time, and occasionally
      associated with lactic and ketoacidemia or with myoglobinuria. Two patients who
      presented neonatally suffered from residual neurological damage with attention
      deficit hyperactive disorder, mild ataxia, motor incoordination, muscle
      hypotonia, and weakness. Nine patients who presented in early childhood or later
      suffered from exertional fatigue between decompensation episodes but were
      otherwise asymptomatic. Two patients died because of intractable metabolic
      acidosis and multi-organ failure. In all patients LAD activity was reduced to 8
      to 21% of the control in muscle or lymphocytes. In four patients LAD protein in
      muscle was reduced to 20 to 60% of the control. Direct sequencing of the cDNA of
      the LAD gene showed that 12 of the 14 mutated alleles carried the G229C mutation
      and two carried an insertion mutation 105insA (Y35X). The patients who presented
      neonatally and had more severe sequelae were compound heterozygotes for the two
      mutations; patients who presented in early childhood or later were homozygous for
      the G229C mutation. Using an allele-specific oligonucleotide hybridization
      technique, nine heterozygotes for the G229C mutation were identified among 845
      anonymous individuals of Ashkenazi Jewish origin disclosing a carrier rate of
      1:94. Because of the significant morbidity associated with the disease, screening
      for the G229C mutation among Ashkenazi Jewish couples should be considered.

PMID- 9934987
TI  - Costello syndrome: report and review.
AB  - We describe a 34-year-old woman with mental retardation, short stature,
      macrocephaly, a "coarse" face, hoarse voice, and redundant skin with deep palmar
      and plantar creases who had evident Costello syndrome. Lacking papillomata, she
      had wart-like lesions of the skin. The previously reported patients with Costello
      syndrome are reviewed. Costello syndrome is probably an autosomal dominant
      disorder, either caused by a mutation in a single gene or by microdeletion.

PMID- 9934989
TI  - Importance of measuring plasma cholesterol precursors.

PMID- 9934988
TI  - Previously apparently undescribed autosomal recessive MCA/MR syndrome with light
      fixation, retinal cone dystrophy, and seizures: the M syndrome.
AB  - We report on two sisters from healthy families with a syndrome of severe
      developmental delay, ataxia, impaired social interaction, a seizure disorder with
      early onset but without epileptiform electroencephalogram changes, and a striking
      light-fixating behavior which was associated with retinal cone dystrophy.
      Additionally, they have minor anomalies including peripheral iris hypoplasia,
      bluish sclerae, mild anteversion of nostrils, micrognathia, ear anomalies, broad
      halluces and thumbs, hypoplastic toenails, short perineal body, "Mongolian
      spots," mild hirsutism, hypoplastic ridges in the hypothenar area, and distal
      axial triradii. Growth and general health are normal in both, but one also had
      tetralogy of Fallot and vesicoureteral reflux. Because this condition appears to
      be previously undescribed we postulate a new autosomal recessive disorder with
      light-fixating behavior and retinal cone dystrophy as leading symptom.

PMID- 9934990
TI  - Increased uptake and transport of cholera toxin B-subunit in dorsal root ganglion
      neurons after peripheral axotomy: possible implications for sensory sprouting.
AB  - In the present study we show that, in contrast to the rat, injection of cholera
      toxin B-subunit (CTB) into the intact sciatic nerve of Macaca mulatta monkey
      gives rise to labelling of a sparse network of fibers in laminae I-II of spinal
      cord and of some mainly small dorsal root ganglion (DRG) neurons. Twenty days
      after sciatic nerve cut, the percentage of CTB-positive lumbar 5 (L5) DRG neuron
      profiles increased from 11% to 73% of all profiles. In the spinal cord, a marked
      increase in CTB labelling was seen in laminae I, II, and the dorsal part of
      lamina III. In the rat L5 DRGs, 18 days after sciatic nerve cut, the percentage
      of CTB- and CTB conjugated to horseradish peroxidase (HRP)-labelled neuron
      profiles increased from 45% to 81%, and from 54% to 87% of all neuron profiles,
      respectively. Cell size measurements in the rat showed that most of the CTB
      positive neuron profiles were small in size after axotomy, whereas most were
      large in intact DRGs. In the rat spinal dorsal horn, a dense network of CTB
      positive fibers covered the whole dorsal horn on the axotomized side, whereas CTB
      labelled fibers were mainly seen in laminae III and deeper laminae on the
      contralateral side. A marked increase in CTB-positive fibers was also seen in the
      gracile nucleus. The present study shows that in both monkey and rat DRGs, a
      subpopulation of mainly small neurons acquires the capacity to take up CTB/CTB
      HRP after axotomy, a capacity normally not associated with these DRG neurons.
      These neurons may transganglionically transport CTB and CTB-HRP. Thus, after
      peripheral axotomy, CTB and CTB-HRP are markers not only for large but also for
      small DRG neurons and, thus, possibly also for both myelinated and unmyelinated
      primary afferents in the spinal dorsal horn. These findings may lead to a
      reevaluation of the concept of sprouting, considered to take place in the dorsal
      horn after peripheral nerve injury.

PMID- 9934991
TI  - DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus
      neurons and reduces atrophy after spinal cord hemisection in adult rats.
AB  - Spinal cord injury in adult mammals causes atrophy or death of some axotomized
      neurons. The product of the antiapoptotic gene Bcl-2 prevents neuron death in
      vivo. We delivered Bcl-2 by intraspinal injection of a DNA plasmid encoding this
      gene to determine if axotomized neurons destined to undergo retrograde death
      could be rescued. Axons of the right side Clarke's Nucleus (CN) were cut
      unilaterally in adult Sprague-Dawley rats by T8 hemisection, leaving the
      contralateral (left) CN as an intact control. Two months postoperatively, there
      was approximately 35% loss of total CN neurons in the right L1 segment. Only 15%
      of large CN neurons (>400 microm2), whose axons project to the cerebellum,
      survived--indicating atrophy and/or death of 85% of these cells. We injected a
      DNA plasmid encoding the human Bcl-2 gene and the bacterial reporter gene LacZ,
      which was complexed with cationic lipids, into the right side of segment T8 of
      the normal spinal cord, or just caudal to the hemisection site. The reporter gene
      was expressed in the perikarya of right CN neurons at L1 for up to 7 days, but
      not 14 days. Two months following T8 hemisection and Bcl-2/LacZ DNA injection,
      there was no significant loss of CN neurons ipsilateral to the lesion.
      Surprisingly, 61% of large neurons survived, indicating partial protection from
      atrophy. In contrast, a DNA plasmid that codes for the LacZ reporter gene, but
      not Bcl-2, did not prevent CN neuron death or atrophy. Administration of the Bcl
      2 gene in adult rats and its expression in these CNS neurons prevents retrograde
      cell death, and also minimizes atrophy. These results may serve as the basis for
      developing novel gene therapy strategies for patients with spinal cord injury.

PMID- 9934992
TI  - Different expressions of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid and N-methyl-D-aspartate receptor subunit mRNAs between visceromotor and
      somatomotor neurons of the rat lumbosacral spinal cord.
AB  - The glutamatergic transmission system plays a key role in afferent and efferent
      pathways involved in micturition. By in situ hybridization combined with
      retrograde Fast Blue labeling, expression of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) receptor (GluR-A to -D) and N-methyl-D-aspartate
      (NMDA) receptor (NR1 and NR2A-D) subunit mRNAs were examined in visceromotor and
      somatomotor neurons of the rat lumbosacral spinal cord. Parasympathetic
      preganglionic neurons (PGNs) in the intermediolateral nucleus highly expressed
      GluR-A and GluR-B subunit mRNAs, with very low levels for GluR-C and GluR-D
      subunits. As for the NMDA receptor, PGNs were associated with abundant signals
      for NR1 subunit mRNA, but without any NR2 subunit mRNAs. On the other hand,
      somatomotor neurons in the ventral horn (dorsolateral nucleus) express all four
      AMPA receptor subunit mRNAs, showing relatively abundant expressions of GluR-C
      and GluR-D subunit mRNA compared with PGNs. In addition to high levels of NR1
      subunit mRNA, dorsolateral nucleus neurons moderately expressed NR2A and NR2B
      subunit mRNAs. These results suggest that molecular organization of both AMPA and
      NMDA receptor channels are distinct between PGNs and dorsolateral nucleus
      neurons. Considering that native NMDA receptors are heteromeric channels composed
      of NR1 and NR2 subunits, it seems likely that dorsolateral nucleus neurons, not
      PGNs, are provided with functional NMDA receptors, which could induce activity
      dependent changes in synaptic transmission in the efferent pathway for the lower
      urinary tract.

PMID- 9934993
TI  - Mu- and delta-opioid receptor mRNAs are expressed in spinally projecting
      serotonergic and nonserotonergic neurons of the rostral ventromedial medulla.
AB  - The rostral ventromedial medulla (RVM) is an important mediator of the
      supraspinal component of opioid antinociception. Previous studies have suggested
      that activation of the cloned mu- and delta-opioid receptors (MOR1 and DOR1
      respectively) in the RVM produces the antinociception mediated by spinally
      projecting neurons. In the present study, we investigated the expression of mRNA
      encoding either MOR1 or DOR1 in the RVM of rats. In addition, we examined
      quantitatively the expression of MOR1 and DOR1 mRNAs in spinally projecting RVM
      neurons including serotonergic (5HT) cells by using in situ hybridization,
      immunocytochemistry, retrograde tract-tracing, and the physical disector.
      Brainstem neurons were labeled in 14 male Sprague-Dawley rats by applying Fluoro
      Gold (FG) topically to the dorsal surface of the lumbosacral spinal cord. Five
      micrometer-thick cryostat sections were cut and in situ hybridization was
      performed by using full-length cRNA probes labeled with 35S-UTP. We found that
      43% of RVM projection neurons expressed MOR1 mRNA and 83% of RVM projection
      neurons expressed DOR1 mRNA. Of 192 retrogradely labeled cells in the RVM, 51
      cells (27%) were immunoreactive for 5HT. Of this population, half appeared to be
      labeled for the mRNA encoding MOR1 and over three-fourths appeared to be labeled
      for the mRNA encoding DOR1. Thus, we conclude that bulbospinal neurons express
      MOR1 and DOR1; moreover, MOR1 and DOR1 are expressed by significant proportions
      of 5HT neurons projecting to or through the dorsal spinal cord.

PMID- 9934994
TI  - Transient CD15 expression reflects stages of differentiation and maturation in
      the human subcortical central auditory pathway.
AB  - The expression of the terminal saccharide determinant CD15 (3[a1-3]-fucosyl-N
      acetyl-lactosamine) was evaluated in the central auditory system of the human
      developing brain by using monoclonal antibodies against this epitope. CD15
      immunoreactivity was first observed in the ventral cochlear nucleus at 10 weeks
      of gestation, whereas the dorsal cochlear nucleus became positive from 13 weeks
      of gestation. In both nuclei, the intensity of immunoreactivity increased until
      16 weeks of gestation and lasted until 25 weeks of gestation. In the inferior
      colliculi, CD15 was poorly expressed in the central nucleus from 13 to 23 weeks
      of gestation and later with moderate levels until birth. Within the medial
      geniculate nucleus, a biphasic pattern of expression was observed with peaks
      around 14-17 and 21-24 weeks of gestation. Heterogeneous expression in the medial
      geniculate nucleus, which was associated either with neurons or the neuropil,
      allowed distinction of subnuclei. In many of the auditory pathway structures
      (e.g., ventral cochlear nucleus and central nucleus of the inferior colliculus),
      a heterogeneous pattern of CD15 expression in the form of repeating parallel
      bands, possibly related to tonotopic organization, became transiently apparent
      around 23 weeks of gestation, whereas in the magnocellular part of the medial
      geniculate nucleus, a striking modular or compartmental arrangement of
      immunoreactive structures (which could also be associated with tonotopic
      organization) was also noted at about 23 weeks of gestation. We propose that the
      initiation of CD15 expression in each nucleus heralds the appearance of
      functional contacts and that high levels of neuropil labeling are related to the
      formation of nonstabilized synaptic contacts. Thus, transient CD15 expression in
      the central auditory system is possibly correlated with phases of functional
      plasticity in this pathway.

PMID- 9934995
TI  - Central and peripheral control of the trigger mechanism for kicking and jumping
      in the locust.
AB  - A crucial stage of the locust kick motor program is the trigger activity that
      inhibits the flexor motorneurons at the end of flexor-extensor coactivation and
      releases the tibia. One source of this inhibition is the M interneuron, which
      produces a spike burst at the time of the trigger activity. Previous work has
      suggested that sensory input resulting from extensor muscle tension may
      contribute to the M spike burst. We find that extensor muscle tension produced
      during thrusting behavior or by direct electrical stimulation with the tibia held
      fixed results in the depolarization of M, but this is not of sufficient amplitude
      to account for the M spike burst during the trigger activity. Furthermore, M
      still produces a spike burst after ablating the sensory systems that produce the
      response to the muscle stimulation. It is concluded that the major component of
      the M trigger activity is central in origin, although sensory feedback from
      extensor muscle tension makes some contribution. The combination of both central
      and peripheral paths for M activation may enhance the robustness of the behavior.

PMID- 9934996
TI  - A distinct thermoreceptive subregion of lamina I in nucleus caudalis of the owl
      monkey.
AB  - An immunohistochemically distinct zone was identified in the superficial aspect
      of trigeminal nucleus caudalis of the New World owl monkey that is not
      immunoreactive for substance P or serotonin, in stark contrast to the dense
      staining present in the surrounding laminae I and II. Thionin-stained sections in
      different planes showed that this is a subregion of lamina I containing clusters
      of neurons that appear to have pyramidal or polygonal somata. Extracellular
      microelectrode recordings in this region revealed clusters of thermoreceptive
      specific (COLD) cells with nasal or labial receptive fields, whereas nociceptive
      neurons were found in the adjacent portions of lamina I. Anterograde tracer
      injections in this region produced trigeminothalamic terminal labeling in the
      site homologous to the lamina I spino-thalamo-cortical relay nucleus identified
      previously in the Old World macaque monkey and in humans. Retrograde tracer
      injections involving this thalamic site, where recordings of trigeminal COLD-like
      neurons were obtained, produced clusters of retrogradely labeled
      trigeminothalamic neurons in this immunohistochemically distinct subregion of
      lamina I, nearly all of which are pyramidal neurons. We conclude that the
      nocturnal owl monkey has a specialized perinasal thermoreceptive
      trigeminothalamic sensory pathway that is probably of behavioral significance
      during olfactory sniffing. In addition, these observations corroborate other
      findings that have indicated that lamina I COLD cells are pyramidal neurons and
      are not physiologically modulated by substance P or serotonin, in contrast to
      nociceptive neurons.

PMID- 9934997
TI  - Distribution of a specific calcium-binding protein of the S100 protein family,
      S100A6 (calcyclin), in subpopulations of neurons and glial cells of the adult rat
      nervous system.
AB  - S100A6 (calcyclin) is a member of the large S100 Ca2+-binding protein family,
      considered to activate several processes along the calcium signal transduction
      pathway including the regulation of cell growth, proliferation, secretion, and
      exocytosis. In the present study, the distribution of S100A6 in the rat nervous
      system was examined by immunohistochemistry with a goat antiserum against
      recombinant human S100A6, which recognizes the rat S100A6 homologue. The main
      S100A6-immunoreactive elements were 1) neuronal somata and dendrites in some
      specific regions of the limbic system (e.g., the basolateral amygdaloid nucleus,
      ventral tip of the CA1-subicular border region, entorhinal cortex, and
      parasubiculum), most of which were identified as a subpopulation of pyramidal
      cells; 2) olfactory receptor cells and olfactory nerve fibers and terminals in
      the olfactory bulb; 3) some tracts of the hindbrain and spinal cord (e.g., the
      spinal trigeminal tract, solitary tract, dorsal root fibers, and the tract of
      Lissauer) and their terminals (e.g., the principal sensory trigeminal nucleus,
      spinal trigeminal nucleus, nucleus of the solitary tract, marginal zone,
      substantia gelatinosa, and proper sensory nucleus of the dorsal horn), as well as
      some sensory neurons of their origins in the dorsal root and trigeminal ganglia;
      4) a subpopulation of astrocytes in the white matter (e.g., the corpus callosum,
      cingulum, external capsule, internal capsule, and fimbria of the hippocampus) and
      around the ventricles; 5) some ependymal cells, especially around the central
      canal; and 6) Schwann cells. These results will improve our understanding of the
      diverse function of Ca2+-binding proteins in the CNS.

PMID- 9934998
TI  - Effects of stimulus frequency and intensity on c-fos mRNA expression in the adult
      rat auditory brainstem.
AB  - Induction of the cellular fos gene (c-fos) is one of the earliest transcriptional
      changes observed following neuronal excitation. Although not an activity marker
      in the strict electrophysiological sense, many neurons in the central nervous
      system increase their c-fos expression after periods of sustained stimulation at
      physiological levels of intensity. In the present study, induction of c-fos mRNA
      expression was examined in the auditory brainstem after 1 hour of continuous free
      field acoustic stimulation. Sprague-Dawley rats were exposed to pure tones of 2,
      8, 16, or 32 kHz or half-octave noise bands centered on 2, 8, or 32 kHz at 80-120
      dB SPL. Stimulation-induced c-fos mRNA expression was evident at all levels of
      the auditory brainstem, and this expression was intensity dependent. In some
      brain areas, induced expression manifested a clear tonotopic organization, i.e.,
      in dorsal, posteroventral, and anteroventral cochlear nuclei, and in the medial
      nucleus of the trapezoid body. The inferior colliculus exhibited multiple
      tonotopic representations. The dorsal nucleus of the lateral lemniscus had a
      crude tonotopy. Although expression was present, tonotopy was not evident in
      periolivary nuclei or in the ventral or intermediate nuclei of the lateral
      lemniscus. Free-field diotic stimulation did not induce c-fos mRNA expression in
      the medial or lateral superior olivary nuclei. Expression was induced in the
      lateral superior olive by dichotic stimulation (after a unilateral cochlear
      ablation), and that expression was tonotopically organized. The results suggest
      that stimulation-induced c-fos mRNA expression can be an effective way of mapping
      neuronal activity in the central auditory system under both normal and
      pathological conditions.

PMID- 9934999
TI  - Cochlear ablation alters acoustically induced c-fos mRNA expression in the adult
      rat auditory brainstem.
AB  - Expression of c-fos mRNA was studied in the adult rat brain following cochlear
      ablations by using in situ hybridization. In normal animals, expression was
      produced by acoustic stimulation and was found to be tonotopically distributed in
      many auditory nuclei. Following unilateral cochlear ablation, acoustically driven
      expression was eliminated or decreased in areas normally activated by the ablated
      ear, e.g., the ipsilateral dorsal and ventral cochlear nuclei, dorsal periolivary
      nuclei, and lateral nucleus of the trapezoid body and the contralateral medial
      and ventral nuclei of the trapezoid body, lateral lemniscal nuclei, and inferior
      colliculus. These deficits did not recover, even after long survivals up to 6
      months. Results also indicated that neurons in the dorsal cochlear nucleus could
      be activated by contralateral stimulation in the absence of ipsilateral cochlear
      input and that the influence of the contralateral ear was tonotopically
      organized. Results also indicated that c-fos expression rose rapidly and
      persisted for up to 6 months in neurons in the rostral part of the contralateral
      medial nucleus of the trapezoid body following a cochlear ablation, even in the
      absence of acoustic stimulation. This response may reflect a release of
      constitutive excitatory inputs normally suppressed by missing afferent input or
      changes in homeostatic gene expression related to sensory deprivation. Instances
      of transient, surgery-dependent increases in c-fos mRNA expression in the absence
      of acoustic stimulation were observed in the superficial dorsal cochlear nucleus
      and the cochlear nerve root on the ablated side.

PMID- 9935000
TI  - 50th anniversary historical article. Ischemic heart disease.

PMID- 9935001
TI  - The Brugada syndrome: clinical, electrophysiologic and genetic aspects.
AB  - This review deals with the clinical, basic and genetic aspects of a recently
      highlighted form of idiopathic ventricular fibrillation known as the Brugada
      syndrome. Our primary objective in this review is to identify the full scope of
      the syndrome and attempt to correlate the electrocardiographic manifestations of
      the Brugada syndrome with cellular and ionic heterogeneity known to exist within
      the heart under normal and pathophysiologic conditions so as to identify the
      cellular basis and thus potential diagnostic and therapeutic approaches. The
      available data suggest that the Brugada syndrome is a primary electrical disease
      resulting in abnormal electrophysiologic activity in right ventricular
      epicardium. Recent genetic data linking the Brugada syndrome to an ion channel
      gene mutation (SCN5A) provides further support for the hypothesis. The
      electrocardiographic manifestations of the Brugada syndrome show transient
      normalization in many patients, but can be unmasked using sodium channel blockers
      such as flecainide, ajmaline or procainamide, thus identifying patients at risk.
      The available data suggest that loss of the action potential dome in right
      ventricular epicardium but not endocardium underlies the ST segment elevation
      seen in the Brugada syndrome and that electrical heterogeneity within right
      ventricular epicardium leads to the development of closely coupled premature
      ventricular contractions via a phase 2 reentrant mechanism that then precipitates
      ventricular tachycardia/ventricular fibrillation (VT/VF). Currently, implantable
      cardiac defibrillator implantation is the only proven effective therapy in
      preventing sudden death in patients with the Brugada syndrome and is indicated in
      symptomatic patients and should be considered in asymptomatic patients in whom
      VT/VF is inducible at time of electrophysiologic study.

PMID- 9935002
TI  - The North American Vasovagal Pacemaker Study (VPS). A randomized trial of
      permanent cardiac pacing for the prevention of vasovagal syncope.
AB  - OBJECTIVES: This study was done to evaluate pacemaker therapy for severe
      recurrent vasovagal syncope. BACKGROUND: Nonrandomized studies have suggested
      that permanent pacing might help control the symptoms of recurrent vasovagal
      syncope. The study goal was to evaluate the effect of permanent pacemaker
      implantation on syncope in patients with frequently recurrent vasovagal syncope.
      METHODS: Patients with > or = 6 lifetime episodes of syncope and with a tilt
      table test that induced syncope or presyncope, as well as a relative bradycardia,
      were randomized to receive a dual-chamber pacemaker or not. The pacemaker
      prevented bradycardia and provided high-rate pacing if a predetermined drop in
      heart rate occurred (rate-drop response). The primary outcome was the first
      recurrence of syncope. Patients also completed a detailed diary recording
      presyncopal episodes. RESULTS: A total of 284 patients was originally planned and
      a pilot study of 60 patients was initiated. At the planned first formal interim
      analysis of efficacy of the pilot study, an unanticipated large treatment effect
      was observed which fulfilled the prespecified criteria for early termination of
      the study. At that time, there were 54 patients enrolled, randomized evenly to no
      pacemaker or to pacemaker. In the no-pacemaker and pacemaker groups the mean ages
      were 40 and 46 years; 74% and 70% patients, respectively, were female. The
      baseline tilt-table test showed a slowest heart <60/min or longest heart period
      >1000 ms in 60% of no-pacemaker patients and 72% of pacemaker patients. There was
      a marked reduction in the postrandomization risk of syncope in pacemaker patients
      (relative risk reduction 85.4%, 95% confidence interval 59.7% to 94.7%;
      2p=0.000022). CONCLUSIONS: Dual-chamber pacing with rate-drop response reduces
      the likelihood of syncope in patients with recurrent vasovagal syncope.

PMID- 9935003
TI  - Cardiac pacing for prevention of vasovagal syncope.

PMID- 9935004
TI  - Sudden death in implantable cardioverter-defibrillator recipients: clinical
      context, arrhythmic events and device responses.
AB  - OBJECTIVES: We sought to investigate the nature of terminal events and potential
      contributory clinical and nonclinical (e.g., device-related) factors associated
      with sudden death (SD) in recipients of an implantable cardioverter-defibrillator
      (ICD). BACKGROUND: The ICD is very effective in terminating ventricular
      tachycardia (VT) or ventricular fibrillation (VF), but protection against SD is
      not absolute. Little is known about the nature and potential causes of SD in
      patients with ICDs. METHODS: We analyzed 25 cases of out-of-hospital SD among
      patients enrolled in the clinical investigation of the Cadence Tiered-Therapy
      Defibrillator System. RESULTS: All patients (24 men and 1 woman, mean age 62+/-10
      years) received epicardial lead systems. The majority (92%) had coronary artery
      disease and a previous myocardial infarction (MI), with a mean left ventricular
      ejection fraction 0.25+/-0.07. At device implantation, the mean defibrillation
      threshold was 13+/-5 J. Sudden death occurred 13+/-11 months later. Twenty
      patients (80%) had received appropriate ICD therapies before death, and 18 (72%)
      were receiving > or = 1 antiarrhythmic drugs at the time of death. Sudden death
      was tachyarrhythmia-associated in 16 patients (64%), non-tachyarrhythmia
      associated in 7 (28%) and indeterminate in 2 (8%). In the 16 patients with
      tachyarrhythmia-associated SD, the overall first therapy success rate in
      tachycardia and fibrillation zones was 60% and 67%, respectively. However,
      despite protracted therapies (> or = 2 shocks) in 7 (66%) of 12 patients who
      received fibrillation therapies, the final tachyarrhythmic episode was ultimately
      terminated by the ICD in 15 (94%) of the 16 patients, whereas 1 patient died
      after multiple (initially successful) internal and external shocks for
      intractable VT/VF during exercise. In 10 patients (40%) one or more, primarily
      clinical, factors potentially contributory to SD were identified: heart failure
      (n=8), angina (n=2), hypokalemia (n=1), adverse antiarrhythmic drug treatment
      (n=1) and acute MI (n=1). An additional 10 patients (40%) had experienced an
      increase in frequency of ICD shocks within 3 months of SD. Appropriate battery
      voltages and normal circuitry function were found in all devices interrogated and
      analyzed after death. CONCLUSIONS: In this select group of patients receiving a
      third-generation ICD, SD was associated with VT or VF events in nearly two-thirds
      of patients, and death occurred despite ultimately successful, although often
      protracted, device therapies. These observations, along with evidence of recent
      worsening clinical status, suggest acute cardiac mechanical dysfunction as a
      frequent terminal factor. In recipients with ICDs, SD directly attributable to
      device failure seems to be rare.

PMID- 9935005
TI  - The influence of ventricular fibrillation duration on defibrillation efficacy
      using biphasic waveforms in humans.
AB  - OBJECTIVES: The purpose of this study was to prospectively investigate the
      influence of ventricular fibrillation (VF) durations of 5, 10 and 20 s on the
      defibrillation threshold (DFT) during implantable cardioverter-defibrillator
      (ICD) implantation. BACKGROUND: Although the DFT using monophasic waveforms has
      been shown to increase with VF duration in humans, the effect of VF duration on
      defibrillation efficacy using biphasic waveforms in humans is not known. METHODS:
      Thirty patients undergoing primary ICD implantation or pulse generator
      replacement were randomly assigned to have the DFT determined using biphasic
      shocks at two durations of VF each (5 and 10 s, 10 and 20 s or 5 and 20 s).
      RESULTS: There was no statistically significant difference in the mean DFT
      comparing VF durations of 5 s (9.5+/-6.0 J) and 10 s (10.8+/-7.0 J) (p=0.4). The
      mean DFT significantly increased from 10.9+/-6.1 J at 10 s of VF to 12.6+/-5.6 J
      (p=0.03) at 20 s of VF, and from 7.0+/-3.5 J at 5 s of VF to 10.5+/-6.3 J
      (p=0.04) at 20 s of VF. An increase in the DFT was observed in 14 patients as VF
      duration increased. There were no clinical characteristics that differentiated
      patients with and without an increase in the DFT. CONCLUSIONS: Defibrillation
      efficacy decreases with increasing VF duration using biphasic waveforms in
      humans. Ventricular fibrillation durations greater than 10 s may negatively
      affect the effectiveness of ICD therapy.

PMID- 9935006
TI  - Role of bipolar electrogram polarity mapping in localizing recurrent conduction
      in the isthmus early and late after ablation of atrial flutter.
AB  - OBJECTIVES: Bipolar electrogram polarity was analyzed to localize the recurrent
      conduction site in the isthmus between the tricuspid annulus (TA) and inferior
      vena cava (IVC) in recurrent atrial flutter (AF). BACKGROUND: Despite the initial
      successful linear isthmus ablation, recurrence of transisthmus conduction and AF
      is not uncommon. It is unclear how the recurrent conduction site can be
      identified. METHODS: Fourteen patients with recurrent AF were studied: four with
      late recurrence remote from the first ablation and 10 with early recurrence
      within 60 minutes after the initial successful ablation. Bipolar electrogram
      polarity mapping was performed during low lateral right atrium (LLRA) pacing
      during sinus rhythm while recording bipolar electrograms from the septal portion
      of the isthmus along the previously ablated line. The septal side of the isthmus
      from TA to IVC was arbitrarily divided into five sites, and the bipolar
      electrodes with cathode at the tip and anode at the second was placed at each
      site. The recurrent conduction site was localized by analyzing the polarity of
      the bipolar electrogram recorded at each site. RESULTS: All recurrent AF was due
      to reentry around TA. During pacing from LLRA, as the mapping electrode was moved
      from TA to IVC side, the major polarity of the electrogram changed from negative
      to positive in all patients. A transitional electrogram with the equal amplitudes
      in positive and negative components was recorded between the sites showing mainly
      negative and positive electrograms, indicating electrogram polarity reversal at
      this site. Application of radiofrequency energy to this single site resulted in
      the elimination of transisthmus conduction in all patients with a single
      application in 11 patients and 2 or 3 in the remaining 3. CONCLUSIONS: Bipolar
      electrogram polarity mapping with attention to the polarity reversal point is
      useful for identifying and ablating the recurrent conduction site.

PMID- 9935007
TI  - Suppression of sustained ventricular tachyarrhythmias: a comparison of d,l
      sotalol with no antiarrhythmic drug treatment.
AB  - OBJECTIVES: This study evaluates the clinical efficacy of d,l-sotalol in patients
      with sustained ventricular tachyarrhythmias. BACKGROUND: D,l-sotalol is an
      important antiarrhythmic agent to prevent recurrences of sustained ventricular
      tachyarrhythmias (VT/VF). However, evidence is lacking that an antiarrhythmic
      agent like d,l-sotalol can reduce the incidence of sustained ventricular
      tachyarrhythmias in comparison to no antiarrhythmic drug treatment. METHODS: A
      prospective study was performed in 146 consecutive patients with inducible
      sustained ventricular tachycardia or ventricular fibrillation. In 53 patients,
      oral d,l-sotalol prevented induction of VT/VF during electrophysiological testing
      and patients were discharged on oral d,l-sotalol (sotalol group). In 93 patients,
      VT/VF remained inducible and a defibrillator (ICD) was implanted. After
      implantation of the device patients were randomly assigned to oral treatment with
      d,l-sotalol (ICD/sotalol group, n=46) or no antiarrhythmic medication (n=47, ICD
      only group). RESULTS: During follow-up, 25 patients (53.2%) in the ICD-only group
      had a VT/VF recurrence in comparison to 15 patients (28.3%) in the sotalol group
      and 15 patients (32.6%) in the ICD/sotalol group (p=0.0013). Therapy with d,l
      sotalol, amiodarone or metoprolol was instituted in 12 patients (25.5%) of the
      ICD-only group due to frequent VT/VF recurrences or symptomatic supraventricular
      tachyarrhythmias. In nine patients, 17% of the sotalol group, an ICD was
      implanted after VT/VF recurrence, three patients (5.7%) received amiodarone.
      Total mortality was not different between the three groups. CONCLUSIONS: D,l
      sotalol significantly reduces the incidence of recurrences of sustained
      ventricular tachyarrhythmias in comparison to no antiarrhythmic drug treatment.

PMID- 9935008
TI  - Efficacy and efficacy testing of sotalol.

PMID- 9935009
TI  - Detection of concealed left sided accessory atrioventricular pathway by P wave
      signal averaged electrocardiogram.
AB  - OBJECTIVES: The purpose of this study was to examine whether P wave signal
      averaged electrocardiogram (P-SAECG), which detects subtle changes in P wave,
      detects the concealed accessory atrioventricular pathway (AP). BACKGROUND: It is
      difficult to differentiate atrioventricular reciprocating tachycardia (AVRT) due
      to the AP from atrioventricular nodal reentrant tachycardia (AVNRT) when the
      ventricular preexcitation is absent on 12-lead electrocardiograms. By
      electrophysiological studies, the anterograde conduction in the concealed AP is
      shown to be blocked near the AP-ventricular interface during sinus rhythm.
      METHODS: P-SAECG during sinus rhythm was performed in 20 normal volunteers
      (control), 21 patients with AVRT due to the concealed AP, 19 with AVNRT, 22 with
      paroxysmal atrial fibrillation (PAF), and 7 with automatic atrial tachycardia
      (AT). The filtered P wave duration (FPD) and AR20 (power spectrum area ratio of 0
      20 to 20-100 Hz) were measured and repeated in AVRT, AVNRT and AT groups at one
      week after catheter ablation. RESULTS: The anterograde conduction in the
      concealed left-sided AP was confirmed in all cases by an electrophysiological
      study. The FPD in AVRT group was more prolonged than that in controls or AVNRT
      group. Although the FPD was similar between AVRT and PAF groups, AR20
      differentiated between the two groups. Ablation of the concealed AP shortened FPD
      in AVRT group but that of the slow pathway or the atrial focus did not shorten in
      the AVNRT or AT groups, respectively. The changes in FPD after ablation were
      correlated with those in the duration of atrial activity by an
      electrophysiological study (r=0.67). CONCLUSIONS: Our findings suggest that P
      SAECG detects the concealed left-sided AP, providing a clinical tool in
      noninvasively assessing atrial activation patterns.

PMID- 9935010
TI  - A comparison of three-year survival after coronary artery bypass graft surgery
      and percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: The purpose of this study was to compare 3-year risk-adjusted
      survival in patients undergoing coronary artery bypass graft (CABG) surgery and
      percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary artery
      bypass graft surgery and angioplasty are two common treatments for coronary
      artery disease. For referral purposes, it is important to know the relative
      pattern of survival after hospital discharge for these procedures and to identify
      patient characteristics that are related to survival. METHODS: New York's CABG
      surgery and angioplasty registries were used to identify New York patients
      undergoing CABG surgery and angioplasty from January 1, 1993 to December 31,
      1995. Mortality within 3 years of undergoing the procedure (adjusted for patient
      severity of illness) and subsequent revascularization within 3 years were
      captured. Three-year mortality rates were adjusted using proportional hazards
      methods to account for baseline differences in patients' severity of illness.
      RESULTS: Patients with one-vessel disease with the one vessel not involving the
      left anterior descending artery (LAD) or with less than 70% LAD stenosis had a
      statistically significantly longer adjusted 3-year survival with angioplasty
      (95.3%) than with CABG surgery (92.4%). Patients with proximal LAD stenosis of at
      least 70% had a statistically significantly longer adjusted 3-year survival with
      CABG surgery than with angioplasty regardless of the number of coronary vessels
      diseased. Also, patients with three-vessel disease had a statistically
      significantly longer adjusted 3-year survival with CABG surgery regardless of
      proximal LAD disease. Patients with other one-vessel or two-vessel disease had no
      treatment-related differences in survival. CONCLUSIONS: Treatment-related
      survival benefit at 3-years in patients with ischemic heart disease is predicted
      by the anatomic extent and specific site of the disease, as well as by the
      treatment chosen.

PMID- 9935011
TI  - Effect of transient abrupt vessel closure during otherwise successful angioplasty
      for unstable angina on clinical outcome at six months. Hirulog Angioplasty Study
      Investigators.
AB  - OBJECTIVES: The objective of this study was to identify predictors of major
      adverse cardiac events after successful coronary angioplasty. BACKGROUND: The
      acute complications of angioplasty are related to baseline clinical and
      angiographic variables, and early complications adversely affect long-term
      outcome. However, the predictors of enduring success after uncomplicated
      angioplasty are less well defined. METHODS: Of 4,098 patients undergoing
      angioplasty in the Hirulog Angioplasty Study, 3,899 (95%) had a successful
      procedure without in-hospital death, emergent bypass surgery or clinical evidence
      of myocardial infarction. Baseline and procedural variables for these 3,899
      patients were examined. RESULTS: Major adverse cardiac events occurred in 22% of
      the patients with initially successful procedures at 6 months: death in 1%,
      myocardial infarction in 2% and repeat revascularization in 21%. Univariable
      predictors of increased events included successful salvage from abrupt vessel
      closure (p < 0.001), emergency stenting (p < 0.001), multilesion angioplasty (p <
      0.001), diabetes (p=0.02), target lesion in the left anterior descending artery
      (p=0.02), unstable angina (p=0.03) and smaller final luminal diameter (p=0.04).
      There was a trend toward increased events among patients with prior angioplasty
      (p=0.08), but asymptomatic elevation of the creatine kinase was not predictive
      (p=0.5). In a multivariable model, abrupt vessel closure was the strongest
      independent predictor of major adverse cardiac events at 6 months (p < 0.001;
      odds ratio [95% confidence interval]=3.6 [2.5 to 5.1]), while multivessel
      angioplasty, target lesion in the left anterior descending artery and diabetes
      also remained independent predictors (all p < or = 0.02). CONCLUSIONS: This
      analysis suggests that "uncomplicated" abrupt vessel closure is a powerful
      predictor of adverse clinical outcome following successful angioplasty. Improved
      techniques to reduce abrupt closure during angioplasty are thus urgently needed,
      and patients who experience "uncomplicated" closure require closer surveillance
      during follow-up.

PMID- 9935012
TI  - The ill wind of transient vessel closure during percutaneous transluminal
      coronary angioplasty.

PMID- 9935013
TI  - Safety of deferring angioplasty in patients with normal coronary flow velocity
      reserve.
AB  - BACKGROUND: In the catheter laboratory there is a need for functional tests
      validating the hemodynamic significance of coronary artery stenosis. OBJECTIVES:
      It was the objective of our study to compare the long-term cardiac event rate and
      the clinical symptoms in patients with reduced coronary flow velocity reserve
      (CFVR) and standard PTCA with patients with normal CFVR and deferred angioplasty.
      METHODS: Our study included 70 patients with intermediate coronary artery
      stenoses (13 f, 57 m; diameter stenosis >50%, <90%) and an indication for PTCA
      due to stable angina pectoris and/or signs of ischemia in noninvasive stress
      tests. CFVR was measured distal to the lesion after intracoronary administration
      of adenosine using 0.014 inch Doppler-tipped guide wires. RESULTS: In 22 patients
      (31%), PTCA was deferred due to a CFVR > or = 2.0 (non-PTCA group). In the
      remaining 48 patients (69%) mean CFVR of 1.4+/-0.23 (p < 0.001) was measured
      (PTCA group). CFVR increased to 2.0+/-0.51 after angioplasty. During follow-up
      (average 15+/-6.0 months), the following major adverse cardiac events (MACE)
      occurred: in the PTCA group re-PTCA was performed in nine patients (18.8%)
      because of unstable angina, five patients (10.4%) suffered an acute myocardial
      infarction (MI) (two infarctions occurred during the angioplasty, three patients
      suffered an infarction during follow-up), two patients (4.2%) needed blood
      transfusions due to severe bleedings, two patients (4.2%) underwent bypass
      surgery and one patient (2.1%) died. In the non-PTCA group, angioplasty was
      necessary only in two cases (9.1%) during follow-up. We did not observe any MI in
      the non-PTCA group. The overall rate of MACE was significantly lower in the non
      PTCA group compared to the PTCA group (9.1% vs. 33.3%, p < 0.01). However, only
      40% of the patients of the non-PTCA group were free of angina pectoris at stress.
      In the PTCA group, 63% did not complain of any symptoms at follow-up (p < 0.05).
      CONCLUSIONS: We conclude that determination of the CFVR is a valuable parameter
      for stratifying the hemodynamic significance of coronary artery stenosis. PTCA
      can safely be deferred in patients with significant coronary stenosis but a CFVR
      > or = 2.0. The total rate of MACE at follow-up was below 10% among these
      patients. However, if PTCA was deferred the number of patients who are free of
      angina is lower compared to those patients who underwent angioplasty.

PMID- 9935014
TI  - Clinical outcomes after detection of elevated cardiac enzymes in patients
      undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin
      (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II.
AB  - OBJECTIVES: We examined the relations of elevated creatine kinase (CK) and its
      myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous
      coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to
      Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a
      trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide. BACKGROUND:
      Elevation of cardiac enzymes often occurs after PCI, but its clinical
      implications are uncertain. METHODS: Patients undergoing elective, scheduled PCI
      for any indication were analyzed. Parallel analyses investigated CK (n=3,535) and
      CK-MB (n=2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days
      and 6 months were stratified by postprocedure CK and CK-MB (multiple of the
      site's upper normal limit). RESULTS: Overall, 1,779 patients (76%) had no CK-MB
      elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in
      323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times
      normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK
      MB was associated with an increased risk of death, reinfarction, or emergency
      revascularization at 30 days, and of death, reinfarction, or surgical
      revascularization at 6 months. Elevated total CK to above three times normal was
      less frequent, but its prognostic significance paralleled that seen for CK-MB.
      The degree of risk correlated with the rise in CK or CK-MB, even for patients
      with successful procedures not complicated by abrupt closure. CONCLUSIONS:
      Elevations in cardiac enzymes, including small increases (between one and three
      times normal) often not considered an infarction, are associated with an
      increased risk for short-term adverse clinical outcomes after successful or
      unsuccessful PCI.

PMID- 9935015
TI  - Chimeric 7E3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients
      undergoing coronary angioplasty.
AB  - OBJECTIVES: The purpose of this study was to monitor the effects of chimeric 7E3
      Fab (ReoPro) on leukocyte and platelet activation and interaction during coronary
      angioplasty. BACKGROUND: Increased expression of CD11b on monocytes and
      neutrophils promotes their adhesion to endothelial cells, extracellular matrix
      and smooth muscle cells. Thrombin-activated platelets adhere via P-selectin to
      monocytes and neutrophils. These cell interactions may affect the outcome of
      coronary angioplasty. METHODS: During coronary angioplasty, venous blood was
      obtained for flow cytometric detection of leukocyte CD11b; platelet CD41a, CD61a
      and CD62P; the percentage of leukocytes with adherent platelets and the intensity
      of bound platelet fluorescence. RESULTS: Leukocyte CD11b expression increased
      after angioplasty in control patients (neutrophils 171+/-25 to 255+/-31 mean
      fluorescence intensity [MFI, mean+/-SEM], n=25, p < 0.0001; monocytes 200+/-40 to
      248+/-36 MFI, n=17, p < 0.05) and decreased in the patients selected to receive
      chimeric 7E3 Fab (neutrophils 146+/-30 to 82+/-22 MFI, n=25, p < 0.0001;
      monocytes 256+/- 53 to 160+/-38 MFI, n= 17, p < 0.05). Neutrophil CD11b decreased
      after in vitro incubation of whole blood with chimeric 7E3 Fab (n=5, p=0.01), but
      fMLP-induced increases in CD11b were not prevented. The CD11b expression was
      unchanged and increased with fMLP stimulation after in vitro incubation of
      isolated neutrophils with chimeric 7E3 Fab. Direct-labeled chimeric 7E3 Fab was
      not detected bound to neutrophils in whole blood or isolated cells using flow
      cytometric techniques. Adhesion of isolated neutrophils to protein-coated glass
      was not prevented by in vitro incubation with chimeric 7E3 Fab. Platelet
      activation increased after angioplasty in control patients (CD62P 8.9+/-0.8 to
      12.3+/-1.2 MFI, n=25, p < 0.05; CD41a 382+/-25 to 454+/-26 MFI, n=25, p < 0.05,
      CD61a 436+/-52 to 529+/-58 MFI, n=11, p < 0.05); it did not increase in the
      patients selected to receive chimeric 7E3 Fab (CD62P 13.2+/-1.0 to 9.0+/-0.9 MFI,
      n=25, p < 0.05; CD61a 398+/-32 to 410+/-38 MFI, n=7, p=NS). Leukocytes with
      adherent platelets tended to increase in the control group of patients and
      decrease after the procedure in patients selected to receive chimeric 7E3 Fab;
      individual and procedure-related variability were marked. CONCLUSIONS: Despite
      standard aspirin and heparin therapy, leukocyte and platelet activation with
      platelet adherence to leukocytes occurs after coronary angioplasty. Although
      chimeric 7E3 Fab does not bind to leukocytes directly, it influences CD11b
      expression in whole blood. Modulation of platelet and leukocyte activation and
      interaction by chimeric 7E3 Fab may contribute to an improved outcome after
      coronary angioplasty.

PMID- 9935016
TI  - Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis
      have therapeutic implications?
AB  - OBJECTIVES: The goal of this review is to reevaluate the unstable coronary
      syndromes in the setting of new therapies and biochemical markers. BACKGROUND:
      Patients with acute coronary syndromes comprise a large subset of many cardiology
      practices. Patients with unstable angina (UA) and non-Q wave myocardial
      infarction (NQMI) may sustain a small amount of myocardial loss but have
      significant amounts of viable, yet ischemic, myocardium, placing them at high
      risk for future cardiac events. In the past, enzyme differentiation of NQMI from
      UA was considered important to assess prognosis and direct therapy. METHODS:
      Manuscripts published in peer-reviewed journals over the past three decades were
      reviewed and selected for this review. Recent abstracts were also considered and
      cited where appropriate. RESULTS: In the late 1990's, although UA and NQMI remain
      parts of a spectrum, it is apparent that the distinction between these two
      entities is no longer sufficient to identify high risk patients; rather, specific
      electrocardiographic changes, aspects of the clinical history, newer biochemical
      markers, and angiographic findings help to better distinguish higher risk
      individuals from a large patient population with unstable coronary syndromes and
      these factors usually determine therapy. CONCLUSIONS: Based on these results, it
      is likely that newer therapies such as glycoprotein IIb/IIIa receptor
      antagonists, low molecular weight heparins, and coronary stents will be directed
      toward these high risk patients.

PMID- 9935017
TI  - Sulfonylurea drugs increase early mortality in patients with diabetes mellitus
      after direct angioplasty for acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to examine the impact of sulfonylurea
      drug use on outcome in diabetic patients undergoing direct coronary angioplasty
      for acute myocardial infarction. BACKGROUND: Sulfonylurea drugs impair ischemic
      preconditioning. Whether sulfonylurea drugs affect outcome adversely in diabetic
      patients undergoing direct angioplasty for acute myocardial infarction is
      unknown. METHODS: Clinical outcomes after direct balloon angioplasty for acute
      myocardial infarction were evaluated in 67 diabetic patients taking oral
      sulfonylurea drugs and 118 diabetic patients not taking these drugs. RESULTS:
      Hospital mortality was significantly higher among diabetics treated with
      sulfonylurea drugs at the time of myocardial infarction (24% vs. 11%). Univariate
      analysis identified sulfonylurea drug, age, ventricular function, ejection
      fraction less than 40%, prior bypass surgery and congestive heart failure as
      correlates of increased in-hospital mortality. Logistic regression found
      sulfonylurea drug use (odds ratio 2.77, p=0.017) to be independently associated
      with early mortality. Congestive heart failure, but not sulfonylurea drug use,
      was associated with an increased incidence of in-hospital ventricular
      arrhythmias. Congestive heart failure, prior bypass surgery and female gender,
      but not sulfonylurea drug use, were associated with late adverse events.
      CONCLUSIONS: Sulfonylurea drug use is associated with an increased risk of in
      hospital mortality among diabetic patients undergoing coronary angioplasty for
      acute myocardial infarction. This early risk is not explained by an increase in
      ventricular arrhythmias, but may reflect deleterious effects of sulfonylurea
      drugs on myocardial tolerance for ischemia and reperfusion. For surviving
      patients sulfonylurea drug use is not associated with an increased risk of
      serious late adverse events.

PMID- 9935018
TI  - Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial.
      Cholesterol And Recurrent Events.
AB  - OBJECTIVES: We sought to assess the influence of baseline lipid levels on
      coronary event rates and the effectiveness of pravastatin therapy in the
      Cholesterol And Recurrent Events (CARE) study. BACKGROUND: The CARE study cohort
      provided a relatively unique opportunity to examine the relation between lipid
      levels and clinical events in a post-myocardial infarction (MI) population with
      relatively low cholesterol and low density lipoprotein (LDL) cholesterol values.
      METHODS: There were 4,159 patients with a previous infarct and a total
      cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and
      triglyceride level <350 mg/dl randomly allocated to placebo (n=2,078) or
      pravastatin 40 mg/day (n=2,081). Time to either coronary death or nonfatal MI
      (primary end point) or to the secondary end point, which included undergoing a
      coronary revascularization procedure, was determined as a function of baseline
      lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride
      levels). RESULTS: Quartile analysis indicated important effects for LDL
      cholesterol, in which a higher LDL was associated with greater cardiac event
      rates (in the placebo group, every 25-mg/dl increment in LDL was associated with
      a 28% increased risk [5% to 56%, p=0.015]) in the primary event. The differential
      event rates with respect to baseline LDL cholesterol for placebo and pravastatin
      groups reduced the difference in clinical outcomes at lower LDL cholesterol
      levels. In both the placebo and pravastatin groups, an inverse relation between
      baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline
      HDL cholesterol level was associated with a 10% [0% to 19%, p=0.046] increase in
      coronary death or nonfatal MI). CONCLUSIONS: Within the LDL cholesterol levels in
      CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in
      the placebo group as well as the clinical effectiveness of pravastatin therapy.

PMID- 9935019
TI  - Risk stratification following myocardial infarction in the thrombolytic era: a
      two-step strategy using noninvasive and invasive methods.
AB  - OBJECTIVES: We prospectively performed a two-step risk assessment in patients in
      the early phase after acute myocardial infarction (MI). BACKGROUND: Noninvasive
      methods like Holter electrocardiographic monitoring (HM) and determination of the
      left ventricular ejection fraction (EF) as well as the invasive technique of
      programmed ventricular stimulation (PVS) have been used to identify patients in
      the late phase after MI as candidates for prophylactic implantation of a
      cardioverter/defibrillator. However, it is unclear whether these results can be
      transferred to patients following acute MI. METHODS: A series of 657 patients
      with acute MI (< or = 75 years) underwent HM and EF. If one of the two methods
      yielded abnormal findings (HM > or = 20 ventricular ectopic beats/h/> or =10
      ventricular pairs/day/ventricular tachycardia; EF < or = 40%), PVS was done
      (abnormal PVS: induction of monomorphic ventricular tachycardia, duration >10 s,
      cycle length > or = 230 ms). RESULTS: Of 657 patients, 304 (46%) had either an
      abnormal HM or EF. The PVS performed in 146 of 304 patients was abnormal in 22.
      During a mean follow-up of 37 months, there were 106 (16%) deaths, being sudden
      in 24 (3.6%), nonsudden cardiac in 45 (6.8%). The incidence of arrhythmic events
      (sudden cardiac death, symptomatic ventricular tachycardia, cardiac arrest) was
      18% (4/22) with an abnormal PVS and only 4% (5/124) with a normal PVS (odds ratio
      4.0, p=0.032). CONCLUSIONS: The rate of arrhythmic events is low in post-MI
      patients in the 1990s. Nevertheless, a two-step risk stratification is helpful in
      selecting candidates for a defibrillator trial aiming at primary prevention of
      sudden cardiac death after MI.

PMID- 9935020
TI  - Effects of early captopril administration after thrombolysis on regional wall
      motion in relation to infarct artery blood flow.
AB  - OBJECTIVES: To determine whether early administration of captopril lessens
      infarct zone regional wall motion abnormalities when infarct artery blood flow is
      abnormal. BACKGROUND: The interaction between angiotensin-converting enzyme (ACE)
      inhibitor therapy, ventricular function and infarct artery blood flow has not
      been well described. METHODS: A total of 493 patients aged < or = 75 years with
      first infarctions, presenting within 4 h of symptom onset, were randomized to
      receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/
      0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60
      min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to
      determine regional wall motion and infarct artery flow. RESULTS: There were no
      differences in ejection fractions or end-systolic volumes between patients
      randomized to receive captopril and those randomized to receive a placebo. Among
      patients with anterior infarction (n = 216), randomization to captopril resulted
      in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward
      fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct
      zone. In patients randomized to receive captopril who had anterior infarction and
      Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer
      hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords
      >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril
      who had anterior infarction and corrected TIMI frame counts > 27 had fewer
      hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below
      normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with
      inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years)
      in the captopril group and 35 in the placebo group (p=0.036). CONCLUSIONS:
      Randomization to receive captopril 2 h after streptokinase improved regional wall
      motion at 3 weeks. The greatest benefit was seen in patients with anterior
      infarction particularly when infarct artery blood flow is reduced.

PMID- 9935021
TI  - Morphological onset and early diagnosis in apical hypertrophic cardiomyopathy: a
      long term analysis with nuclear magnetic resonance imaging.
AB  - OBJECTIVES: A long-term follow-up study with nuclear magnetic resonance (NMR)
      imaging was undertaken to detect the morphological onset and to establish the
      early diagnosis in apical hypertrophic cardiomyopathy (HCM). BACKGROUND: A
      spadelike configuration on left ventriculogram (LVG) is regarded as a diagnostic
      criterion for the classical apical HCM. There also exists a segmented hypertrophy
      at the apical level without indicating the spadelike features (a nonspade
      configuration). To detect the hypertrophied myocardium of the nonspade
      configuration, circumferential scrutiny of the apex is required. Although both
      configurations can be underlying causes of giant negative T waves, etiological
      relationship between the two is not clarified. METHODS: The criteria for the
      spadelike configuration defined on left ventricular short-axis NMR images were as
      follows: (apical maximal thickness > or = 15 mm), (apical anterior thickness over
      basal anterior thickness > or = 1.3) and (apical posterior thickness over basal
      posterior thickness > or =1.3). Thirteen patients who had predominant hypertrophy
      (> or = 15 mm) at the apical level without the spadelike configuration underwent
      NMR imaging twice before and after 54+/-10 months' follow-up. RESULTS: Apical
      hypertrophy that had been confined to the lateral wall in four, the anterior
      lateral wall in two, and the septal-anterior wall in one developed to become
      circumferential hypertrophy that fulfilled the criteria for the spadelike
      configuration after the follow-up period. CONCLUSIONS: The spadelike
      configuration can begin with the nonspade configuration and therefore, both can
      constitute a single disease entity of apical HCM. The early diagnosis of apical
      HCM can be achieved by identifying the hypertrophy frequently confined to the
      lateral wall at the apical level.

PMID- 9935022
TI  - The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic
      blood vessels of patients attending for redo and first time coronary artery
      bypass graft surgery.
AB  - OBJECTIVES: To determine if Chlamydia pneumoniae (C. pneumoniae) is more
      prevalent in atherosclerotic compared with normal blood vessels of patients
      requiring redo and first time coronary artery bypass graft surgery (CABG).
      BACKGROUND: Serological and pathological studies have associated atherosclerosis
      with C. pneumoniae infection. As atherosclerosis is one of the causes of graft
      failure following CABG, then it may be expected that the prevalence of the
      organism in failed grafts and diseased native vessels should be greater than in
      the new grafts. METHODS: Endarterectomy specimens and failed and new grafts were
      collected from 49 patients with late graft failure. Endarterectomy specimens and
      new grafts were also collected from nine patients having first time CABG. The
      presence of C. pneumoniae DNA was then checked for using a nested polymerase
      chain reaction. RESULTS: The prevalence of C. pneumoniae DNA in failed venous
      grafts (38.2%) was similar to that in endarterectomy specimens from native
      coronary arteries (38.5%) and greater than that in new saphenous vein grafts
      (11.8%). However, it was similar to that in new internal mammary artery grafts
      (30.0%). Also, the interval between surgery in redo patients was the same
      regardless of whether C. pneumoniae was present or not. CONCLUSIONS: Cross
      sectional studies cannot determine whether C. pneumoniae is a cause of
      atherosclerosis since they do not show whether infection precedes or follows its
      development. However, our results suggest that the organism is not an important
      factor in graft failure or atherosclerosis.

PMID- 9935023
TI  - Association between apolipoprotein(a) phenotypes and coronary heart disease at a
      young age.
AB  - OBJECTIVES: The purpose of this study was to investigate lipoprotein(a) [Lp(a)]
      levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of
      coronary heart disease (CHD). BACKGROUND: Although Lp(a) levels have been
      extensively analyzed in relation to age of CHD, apo(a) phenotypes have not.
      METHODS: Three hundred and thirty-five consecutive CHD patients were enrolled and
      grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55
      years). RESULTS: In each patient group Lp(a) levels were higher than in an age
      matched control group, but among the patient groups no differences in Lp(a)
      levels were observed. Apolipoprotein(a) phenotype distributions showed
      significant differences between patients and age-matched control subjects. Among
      the patient groups the difference in percentage of subjects with two apo(a)
      isoforms of low molecular weight (MW) was highly significant (p < 0.001).
      Multivariate analysis showed that apo(a) phenotypes were the best predictors of
      early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of
      at least one apo(a) isoform of low MW for CHD declined with age; in particular
      apo(a) phenotypes had their highest predictive value in younger persons (OR:
      14.62). The OR for the presence of two isoforms of low MW/presence of only
      isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45
      to 54 years and 15.83 in the older age group. CONCLUSIONS: The present article
      reports the first evidence of a strong independent association of apo(a)
      phenotypes with the age of onset of CHD. Thus, if our data are confirmed by
      larger studies, apo(a) phenotypes might be used together with Lp(a) levels as
      powerful genetic markers in assessing the actual risk of developing CHD at a
      young age.

PMID- 9935025
TI  - Outcomes research: evaluating the impact of echocardiography in congestive heart
      failure.

PMID- 9935024
TI  - Use of echocardiography in the management of congestive heart failure in the
      community.
AB  - OBJECTIVES: We evaluated the use and the impact of echocardiography in patients
      receiving an initial diagnosis of congestive heart failure in Olmsted County,
      Minnesota, in 1991. BACKGROUND: The American College of Cardiology/American Heart
      Association clinical practice guidelines recommend echocardiography in all
      patients with suspected congestive heart failure. No data are available on use
      and impact of echocardiography in management of congestive heart failure in a
      community. METHODS: The medical records linkage system of the Rochester
      Epidemiology Project was used to identify all 216 patients who satisfied the
      Framingham criteria for congestive heart failure. Of these, 137 (63%) underwent
      echocardiography within 3 weeks before or after the episode of congestive heart
      failure (Echo group), and the other 79 patients constitute the No-Echo group.
      RESULTS: The No-Echo group patients were older (p=0.022), were more likely to be
      female (p=0.072), had milder symptoms (p=0.001) and were less often hospitalized
      at diagnosis (p=0.001). Fewer patients in the No-Echo group were treated with
      angiotensin-converting enzyme inhibitors (p=0.001). Advanced age (> or = 80
      years), lower New York Heart Association functional class, absence of a fourth
      heart sound on examination, absence of cardiomegaly or signs of congestive heart
      failure on chest radiography and absence of known valve disease were
      independently related to the decision not to obtain an echocardiogram. Survival
      after adjustment for age, functional class and gender was lower in the No-Echo
      group than the Echo group (risk ratio=0.607, p=0.017). CONCLUSIONS: The underuse
      of echocardiography appears to be associated with poorer survival and underuse of
      angiotensin-converting enzyme inhibitor therapy.

PMID- 9935026
TI  - Exercise intolerance in patients with chronic heart failure and increased
      expression of inducible nitric oxide synthase in the skeletal muscle.
AB  - OBJECTIVES: This study was designed to analyze the effect of iNOS on
      mitochondrial creatine kinase (mi-CK) expression and exercise capacity in chronic
      heart failure (CHF). BACKGROUND: The molecular mechanisms underlying exercise
      intolerance in CHF are still unclear. Expression of inducible nitric oxide
      synthase (iNOS) and reduced phosphocreatine resynthesis have been described in
      skeletal muscle of patients with CHF. However, it is unknown whether these
      phenomena are causally related to each other and to exercise tolerance. METHODS:
      Thirty-eight patients with CHF and 8 healthy controls (C) underwent bicycle
      ergospirometry and biopsy of the vastus lateralis muscle. Expression of iNOS was
      quantified by immunohistochemistry and reverse-transcriptase polymerase chain
      reaction, mi-CK by Western-blot. Intracellular presence of NO was confirmed by
      immunohistochemical quantification of nitrotyrosine (NT). To corroborate clinical
      findings, L6 rat skeletal myoblasts were incubated with sodium nitroprusside
      (SNP). RESULTS: Expression of iNOS was significantly increased in CHF (4.0+/-2.8
      vs. 0.8+/-0.7% iNOS positive tissue area, p < 0.001 vs. C) and inversely
      correlated to maximal oxygen uptake (r=-0.65, p < 0.001). Intracellular NO
      accumulation was confirmed by increased NT levels (13.5+/-8.5 vs. 2.0+/-1.7% NT
      positive tissue area, p < 0.001 vs. C). Mi-CK was decreased in CHF (0.84+/-0.36
      vs. 1.57+/-0.60, p < 0.001 vs. C). The inverse correlation seen between iNOS and
      mi-CK expression in patients (r=-0.68, p < 0.001) was reproduced in incubation
      experiments with SNP. CONCLUSIONS: Increased expression of iNOS in skeletal
      muscle of patients with CHF was inversely correlated with mi-CK expression and
      exercise capacity. Cell experiments confirmed a causal relationship via NO. These
      findings extend our knowledge of the pathophysiology of exercise intolerance in
      CHF.

PMID- 9935027
TI  - Ejection fraction by radionuclide ventriculography and contrast left
      ventriculogram. A tale of two techniques. SAVE Investigators. Survival and
      Ventricular Enlargement.
AB  - OBJECTIVES: We assessed the abilities of two methods to measure ejection fraction
      (EF)-radionuclide ventriculography (RVG) and contrast left ventriculography (Cath
      EFa) to predict cardiovascular events. BACKGROUND: Both RVG and Cath-EFa are
      commonly used methods to measure left ventricular performance and assess
      prognosis. Their comparative abilities to predict clinical events have not been
      reported. METHODS: Both RVG EF and Cath-EFa were measured within 16 days of
      myocardial infarction (MI) in 688 patients. The results were divided into
      terciles. Prognosis by terciles was assessed for each technique. A multivariate
      analysis was performed to determine which EF measurement was a better predictor
      of prognosis. RESULTS: Average RVG-EF was 32%+/-7, while Cath-EFa was 42%+/-10.
      Both RVG and Cath-EFa were poorly correlated (R=0.42). Event rate declined across
      terciles with increasing EF for both techniques (events in lowest to highest
      tercile of Cath-EFa 40.7%, 25.9%, 11.6%, p < 0.001; and RVG-EF 39.9%, 26.1%,
      15.6%, p < 0.001). There was concordance of terciles in 303 of 688 patients
      (44%). When patients in the highest RVG terciles were in the highest Cath-EFa
      tercile, the event rate was 7%. However, when patients in the highest RVG
      terciles were in the lowest Cath-EFa tercile, the event rate was 19%. Both Cath
      EFa (p < 0.001) and RVG-EF (p < 0.001) were independent predictors of
      cardiovascular events. CONCLUSIONS: Ejection fraction measured by RVG or during
      catheterization is a valuable tool in the risk stratification of postinfarct
      patients. When disagreement is present between clinical impression and
      measurement by either method, the use of an alternative measurement is warranted
      and complementary.

PMID- 9935029
TI  - Chronotropic competence in endurance trained heart transplant recipients: heart
      rate is not a limiting factor for exercise capacity.
AB  - OBJECTIVES: The purpose of this study was to show that the chronotropic potential
      of the well trained heart transplant recipient (HTR) does not limit exercise
      capacity. BACKGROUND: Chronotropic incompetence is considered to be the main
      limiting factor of the functional capacity of heart transplant recipients.
      However, no systematic study had been published on patients who had spontaneously
      undergone heavy endurance training for several years. METHODS: Heart rate (HR)
      and respiratory gas exchanges (VO2, VCO2, VE) were measured in 14 trained HTRs (T
      HTRs) during exercise tests on a bicycle, on a treadmill and by Holter
      electrocardiography during a race. RESULTS: Peak values observed in T-HTRs during
      the treadmill test were higher than those reached during the bicycle test
      (VO2peak: 39.8+/-6.9 vs. 32.5+/-7.8 ml x kg(-1) x min(-1), p < 0.001; HRpeak:
      169+/-14 vs. 159+/-16 bpm, p < 0.01). During treadmill exercise VO2peak and
      HRpeak values observed were very close to the mean predicted VO2pmax and HRpmax.
      The maximum heart rate during the race (HRrace) was greater than HRpeak values
      during the treadmill test (179+/-14 vs 169+/-14 bpm, p < 0.01) and slightly above
      the mean predicted values (HRrace/HRpmax X 100 = 101+/-10%). The treadmill
      exercise test yields more reliable data than does the bicycle test. CONCLUSIONS:
      Extensive endurance training enables heart transplant recipients to reach
      physical fitness levels similar to those of normal sedentary subjects; heart rate
      does not limit their exercise capacity.

PMID- 9935028
TI  - Cardiac and systemic sympathetic activity in response to clonidine in human heart
      failure.
AB  - OBJECTIVES: We studied the effects of clonidine on cardiac sympathetic activity
      and left ventricular function in patients with congestive heart failure (CHF).
      BACKGROUND: Sympathetic activation has major prognostic implications in patients
      with heart failure. Clonidine, an imidazoline and alpha2-receptor agonist, has
      been shown to cause a reduction in generalized sympathetic activity. METHODS:
      Nine patients with CHF (left ventricular ejection fraction 22+/-4% [mean+/-SEM])
      received a 50 microg and 100 microg bolus of clonidine intravenously. Study
      measurements included right and left heart hemodynamics, cardiac output, rate of
      rise in left ventricular peak positive pressure (LV + dP/dt) and tau, along with
      cardiac and total body norepinephrine spillover. The radiotracer method was used
      for calculation of norepinephrine spillover. RESULTS: Right and left heart
      filling pressures did not change in response to either dose of clonidine. Mean
      arterial pressure fell after the second dose of clonidine, from 94+/-8 to 82+/-6
      mm Hg (p < 0.05). The LV + dP/dt was reduced from 737+/-53 to 629+/-43 mm Hg/s (p
      < 0.05). Clonidine also caused a significant increase in tau, as measured by the
      method of Weiss (65+/-3 vs. 74+/-4 ms, p < 0.01) and the direct pressure half
      time technique (48+/-2 vs. 54+/-3 ms, p < 0.01). Cardiac norepinephrine spillover
      fell from 121+/-29 to 52+/-20 pmol/min in response to 100 microg of clonidine (p
      < 0.01 vs. control). CONCLUSIONS: Despite a significant fall in arterial
      pressure, clonidine caused a marked reduction in sympathetic activity directed at
      the heart. The negative inotropic and lusitropic effects appear to be secondary
      to this reduction in sympathetic drive. Because increased cardiac and generalized
      sympathetic activity are strong predictors of an adverse outcome in patients with
      CHF, the role of centrally active sympathoinhibitory agents in the therapy of CHF
      deserves further exploration.

PMID- 9935030
TI  - Histological evaluation of coronary plaque in patients with variant angina:
      relationship between vasospasm and neointimal hyperplasia in primary coronary
      lesions.
AB  - OBJECTIVES: This study was designed to determine whether coronary vasospasm in
      patients with variant angina pectoris (VAP) may produce focal organic lesions at
      the site of vasospasm that would contribute to disease progression. BACKGROUND:
      Recent clinical angiographic and experimental studies have demonstrated the
      potential role of vasospasm in the worsening of organic coronary stenosis.
      METHODS: We studied histologically the coronary plaques obtained at atherectomy
      in 202 patients with moderate to severe coronary stenosis. This population
      included 22 patients with VAP, 100 patients with chronic stable angina and 80
      patients with restenosis following angioplasty or atherectomy. Diagnosis of VAP
      was based on both the clinical feature of angina at rest associated with ST
      elevation and a positive response to acetylcholine provocation test. RESULTS: The
      most common histological appearance in 92% of patients with stable angina was
      hypocellular fibroatheromatous plaques, whereas neointimal hyperplasia was the
      characteristic feature of the plaque observed in 90% of patients with restenosis.
      The coronary specimens at the site of spasm in 15 of the 22 patients (68%) with
      VAP demonstrated intimal injuries such as neointimal hyperplasia (15), thrombus
      formation (2), and intimal hemorrhage (3). Neointimal hyperplasia was
      significantly more common in the patients with VAP as compared with those with
      stable angina (68% vs. 8%; p < 0.0001). A rapid progression of organic stenosis
      within three years was angiographically found in 5 of the 22 patients with
      variant angina. In all five cases, neointimal hyperplasia was the main
      contributor to the worsening of the organic lesion at the site of spasm. These
      histological findings in patients with VAP extremely resembled those in
      restenosis. Except for vasospasm, no factors significantly predicted the presence
      of neointimal formations in primary coronary lesions. CONCLUSIONS: Coronary
      vasospasm may provoke vascular injury that leads to the formation of neointima in
      VAP patients similar to that seen with restenosis. Coronary spasm may thus play a
      key role in the rapid coronary stenosis progression in certain patients with VAP.

PMID- 9935031
TI  - Prognosis of completely asymptomatic adult patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVES: We investigated the long-term prognosis of completely asymptomatic
      adult patients with hypertrophic cardiomyopathy (HC). Diagnosis of HC was
      suspected because of an abnormal electrocardiogram and/or cardiac murmur and
      confirmed by echocardiography and/or left ventricular angiography, and
      hemodynamic investigation. BACKGROUND: Hypertrophic cardiomyopathy shows marked
      heterogeneity in clinical expression and prognosis. The prognosis of asymptomatic
      patients with HC has not been fully defined. METHODS: Of 128 consecutive adult
      patients with HC, 58 asymptomatic patients (Group 1, mean age 42.8 years) and 70
      symptomatic patients (Group 2, mean age 50.4 years) were studied to assess
      cardiac mortality. Mean follow-up periods were 11.0 years for Group 1 and 9.1
      years for Group 2. RESULTS: At presentation, Group 1 patients were younger and
      had smaller left atrial dimensions than did Group 2 patients. The annual cardiac
      mortality rate and the rate for sudden death alone in Group 1 were significantly
      lower than in Group 2 (0.9% vs. 1.9%, p < 0.05, 0.1% vs. 1.4%, p < 0.05,
      respectively). Although about one-third of the survivors in Group 1 had cardiac
      symptoms at their most recent evaluation, only one patient died suddenly compared
      with eight in Group 2. The annual mortality rate due to heart failure was similar
      in each group. Only a syncopal episode was associated with both cardiac death and
      sudden death for both groups combined. CONCLUSIONS: The cardiac mortality rate
      for completely asymptomatic adult patients with HC was very low, significantly
      lower than that of symptomatic patients, and there was a disproportionately low
      incidence of sudden death.

PMID- 9935032
TI  - Left atrial filling volume can be used to reliably estimate the regurgitant
      volume in mitral regurgitation.
AB  - OBJECTIVES: The objective was to analyze the accuracy and diagnostic value of the
      estimated regurgitant volume of mitral regurgitation using 1) left atrial volume
      variation during ventricular systole (left atrial filling volume) and 2) the
      percent of systolic pulmonary vein velocity integral compared with its total.
      BACKGROUND: Left atrial filling volume (LAfill), which represents the atrial
      volume variation during ventricular systole, has been used for the assessment of
      mitral regurgitation severity. A good correlation with invasive semiquantitative
      evaluation was found, but with an unacceptable overlapping among grades. The
      reason could be the absence of information concerning the contribution of blood
      entering into the left atrium from the pulmonary veins. METHODS: Doppler
      regurgitant volume (Dpl-RVol) (mitral stroke volume - aortic stroke volume) was
      measured in 30 patients with varying degrees and etiological causes of mitral
      regurgitation. In each patient atrial volumes were measured from the apical view,
      using the biplane area-length method. The systolic time-velocity integral of
      pulmonary vein flow was expressed as a percentage of the total (systolic
      diastolic) time-velocity integral (PVs%). These parameters were used in this
      group of patients to obtain an equation whose reliability in estimating Dpl-RVol
      was tested in a second group of patients. RESULTS: In the initial study group,
      with linear regression analysis the following parameters correlated with Dpl
      RVol: end-systolic left atrial volume (R2=0.37, p=0.0004); LAfill (R2=0.45, p <
      0.0001); PVs% (R2=0.56, p < 0.0001). In multiple regression analysis the
      combination of LAfill and the percent of the systolic pulmonary vein velocity
      integral (PVs%) provided a more accurate estimate of regurgitant volume (R2=0.88;
      SEE 10.6; p < 0.0001; Dpl-RV=6.18 + (1.01 x LAfill) - (0.783 x PVs%). The
      equation was subsequently tested in 54 additional patients with mitral
      regurgitation with a mean Dpl-RVol 27+/-37 ml. Estimated regurgitant volume and
      Dpl-RVol correlated well with each other (R2=0.90; SEE 12.1; p < 0.0001). In the
      test population, the equation was 100% sensitive and 98% specific in detecting a
      regurgitant volume higher than 55 ml. CONCLUSIONS: Left atrial filling volume and
      pulmonary vein flow give a reliable estimate of regurgitant volume in mitral
      regurgitation.

PMID- 9935033
TI  - Left atrial filling revisited: a noninvasive index in quantifying the severity of
      mitral regurgitation.

PMID- 9935034
TI  - Noncardiac surgery in Eisenmenger syndrome.
AB  - OBJECTIVES: The purpose of this study was to evaluate the morbidity and mortality
      associated with noncardiac surgery (NCS) in patients (pts) with Eisenmenger
      syndrome. BACKGROUND: Noncardiac surgery in pts with Eisenmenger syndrome is
      associated with increased cardiovascular complications. METHODS: Fifty-eight pts
      with Eisenmenger syndrome (17M, 41F aged 18 to 69 years (mean 41 years) who had
      been followed for up to 41.5 years (mean 9.3 years) were retrospectively
      evaluated for any NCS done at > or = 17 years of age. RESULTS: Twenty-four pts
      had a total of 28 NCSs at an age of 17 to 55 years (mean 29 years) including 9
      tubal ligations, 3 neurosurgeries, 3 cholecystectomies, 3 hysterectomies, 3
      vasectomies, and 1 each spinal fusion, appendectomy, eye enucleation, hernia
      repair, hand surgery, tonsillectomy and therapeutic abortion. There were two
      deaths (7%), one following spinal fusion and the other following appendectomy at
      another institution. Fourteen of these NCSs were performed at our institution,
      including 11 under general anesthesia. The duration of anesthesia varied from 75
      to 525 min (mean 165 min). All pts remained in sinus rhythm. The lowest systolic
      blood pressure (BP) ranged from 78 to 125 mm Hg. Of those 11 pts, 9 were
      extubated immediately after surgery and 2 needed dopamine. Ten patients were
      discharged without any complications, including 3 within 1 day of surgery. One
      death occurred 10 days following spinal fusion. This pt had the longest
      anesthesia (525 min) and an intraoperative systolic BP as low as 78 mm Hg. She
      also needed the largest fluid administration (6,475 cc) in addition to
      postoperative mechanical ventilation and dopamine. CONCLUSIONS: Adult pts with
      Eisenmenger syndrome are at increased risk with NCS, but with current/modern
      techniques, the risk of death is less than previously thought. In the vast
      majority of cases, NCS can be undertaken without substantial morbidity, and early
      extubation is achievable. However, even with relatively minor surgery,
      significant complications, including death, can occur. Referral to major centers
      with expertise in the care of pts with Eisenmenger syndrome is advisable.

PMID- 9935035
TI  - Echocardiographic diagnosis alone for the complete repair of major congenital
      heart defects.
AB  - OBJECTIVES: The study was done to determine the diagnostic accuracy of
      echocardiography alone in the preoperative diagnosis of children with major
      congenital heart defects undergoing primary complete repair. BACKGROUND: Although
      echocardiography is well established as the first-line imaging technique for the
      diagnosis of all forms of congenital heart disease, most institutions continue to
      perform cardiac catheterization prior to complete repair of more complex defects.
      METHODS: To determine the diagnostic accuracy of echocardiography alone and
      echocardiography plus catheterization, we reviewed the records of 503 children
      with major congenital heart defects who underwent primary complete repair at our
      institution between July 1992 and June 1997. We included children with
      transposition of the great arteries, tetralogy of Fallot, double-chamber right
      ventricle, interrupted aortic arch, aortic coarctation, atrioventricular septal
      defect, truncus arteriosus, aortopulmonary septal defect, and totally anomalous
      pulmonary venous return. We excluded children with less complex defects such as
      isolated shunt lesions, as well as those with the most complex defects that would
      require surgical palliation (e.g., functional univentricular heart). We defined
      major errors as those that increased the surgical risk and minor errors as those
      that did not. Errors in diagnosis were determined at surgery. RESULTS: Eighty-two
      percent of children (412 of 503) underwent surgery after preoperative diagnosis
      by echocardiography alone. There were 9 major (2%) and 10 minor errors in the
      echocardiography alone group and 7 major and 5 minor errors in the
      echocardiography plus catheterization group. The most common type of error was
      misidentification of coronary artery anatomy in patients with transposition of
      the great arteries. No error in either group resulted in surgical morbidity or
      mortality. CONCLUSIONS: This study suggests that echocardiography alone is an
      accurate tool for the preoperative diagnosis of major congenital heart defects in
      most children undergoing primary complete repair, and may obviate the need for
      routine diagnostic catheterization.

PMID- 9935036
TI  - Pravastatin sodium activates endothelial nitric oxide synthase independent of its
      cholesterol-lowering actions.
AB  - OBJECTIVES: We tested the hypothesis that pravastatin (PRA) activates endothelial
      nitric oxide synthase (eNOS). BACKGROUND: Pravastatin has been found to have
      clinical benefits beyond those predicted by its actions in reducing plasma low
      density lipoprotein cholesterol (LDL). Both PRA and simvastatin (SIM) are equally
      effective in reducing LDL, but only PRA reduces platelet aggregation and is an
      effective vasodilator. Nitric oxide (NO) also inhibits platelet aggregation and
      vasodilates. METHODS: We determined PRA and SIM effects on vasorelaxation in
      aortic rings and NO production by cultured bovine aortic endothelial cells.
      Nitric oxide was measured by using a NO electrode and by an assay for conversion
      of hemoglobin to methemoglobin. Specificity of NOS activation was tested by using
      the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 1 mmol/liter) in the
      presence or absence of excess L-arginine (L-ARG, 1 mmol/liter). RESULTS:
      Endothelium-dependent vasorelaxation was maximal with acetylocholine (ACH, 100%),
      followed by PRA (62.8%) and then SIM (37.1%). Direct measurement of NO confirmed
      that vasorelaxation is due to NO release and showed that PRA and ACH had similar
      dose-dependent effects on NO production, while SIM was only 25% to 30% as
      effective. Methemoglobin assay confirmed these results and demonstrated their
      specificity for NOS activity. The L-NAME blunted the responses to 45% of initial
      values. Excess L-ARG reversed this effect and potentiated NO production to 133%
      of initial levels. CONCLUSIONS: Both PRA and SIM activate eNOS, but SIM is much
      less effective. Clinical benefits with PRA not explained by LDL reductions may be
      the result of an independent action of PRA on eNOS activation.

PMID- 9935037
TI  - A Ca channel blocker, benidipine, increases coronary blood flow and attenuates
      the severity of myocardial ischemia via NO-dependent mechanisms in dogs.
AB  - OBJECTIVES: This study was undertaken to examine whether a dihydropyridine Ca
      channel blocker, benidipine, increases cardiac NO levels, and thus coronary blood
      flow (CBF) in ischemic hearts. BACKGROUND: Benidipine protects endothelial cells
      against ischemia and reperfusion injury in hearts. METHODS AND RESULTS: In open
      chest dogs, coronary perfusion pressure (CPP) of the left anterior descending
      coronary artery was reduced so that CBF decreased to one-third of the control
      CBF, and thereafter CPP was maintained constant (103+/-8 to 42+/-1 mmHg). Both
      fractional shortening (FS: 6.1+/-1.0%) and lactate extraction ratio (LER: -41+/
      4%) decreased. Ten minutes after the onset of an intracoronary infusion of
      benidipine (100 ng/kg/min), CBF increased from 32+/-1 to 48+/-4 ml/100g/ min
      during 20 min without changing CPP (42+/-2 mmHg). Both FS (10.7+/-1.2%) and LER (
      16+/-4%) also increased. Benidipine increased cardiac NO levels (11+/-2 to 17+/-3
      nmol/ml). The increases in CBF, FS, LER and cardiac NO levels due to benidipine
      were blunted by L-NAME. Benidipine increased cyclic GMP contents of the coronary
      artery of ischemic myocardium (139+/-13 to 208+/-15 fmol/mg protein), which was
      blunted by L-NAME. CONCLUSION: Thus, we conclude that benidipine mediates
      coronary vasodilation and improves myocardial ischemia through NO-cyclic GMP
      dependent mechanisms.

PMID- 9935038
TI  - Role of microtubules in the contractile dysfunction of hypertrophied myocardium.
AB  - OBJECTIVES: We sought to determine whether the ameliorative effects of
      microtubule depolymerization on cellular contractile dysfunction in pressure
      overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective
      and persistent increase in microtubule density causes decreased contractile
      function of cardiocytes from cats with hypertrophy produced by chronic right
      ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine
      normalizes contractility in these isolated cardiocytes. However, whether these
      changes in cellular function might contribute to changes in function at the more
      highly integrated and complex cardiac tissue level was unknown. METHODS:
      Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure
      overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25
      control cats. Contractile state was measured using physiologically sequenced
      contractions before and 90 min after treatment with 10(-5) mol/liter colchicine.
      RESULTS: The PAB significantly increased RV systolic pressure and the RV
      weight/body weight ratio in PAB; it significantly decreased developed tension
      from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from
      0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and
      shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB.
      Indirect immunofluorescence confocal microscopy showed that PAB muscles had a
      selective increase in microtubule density and that colchicine caused complete
      microtubule depolymerization in both control and PAB papillary muscles.
      Microtubule depolymerization normalized myocardial contractility in papillary
      muscles of PAB cats but did not alter contractility in control muscles.
      CONCLUSIONS: Excess microtubule density, therefore, is equally important to both
      cellular and to myocardial contractile dysfunction caused by chronic, severe
      pressure-overload cardiac hypertrophy.

PMID- 9935040
TI  - Effect of congestive heart failure on in vivo canine aortic elastic properties.
AB  - OBJECTIVES: The aim of this study was to characterize fully in vivo aortic
      compliance over a wide range of passive distending pressures, and to study
      pharmacologically induced alterations in compliance using an intravascular
      ultrasound-based technique in the canine model of heart failure. BACKGROUND:
      Altered aortic compliance may influence considerably the function of the failing
      heart. Although some studies demonstrate that patients with heart failure have
      decreased aortic compliance, data from other studies are conflicting. METHODS:
      Aortic pressures and dimensions in seven dogs were determined both before and
      after pacing-induced congestive heart failure (CHF) using simultaneous
      micromanometer and intravascular ultrasound transducers. Decreases in aortic
      pressure were produced at baseline and after nitroprusside and dobutamine
      infusions. Inner and outer aortic circumferences were drawn at the lumen-intimal
      and media-adventitial borders. RESULTS: Aortic pressure-dimension (chamber)
      stiffness constants were greater after heart failure was produced (10.0+/-1.5 vs.
      6.7+/-1.5, p < 0.05), but stress-strain stiffness (material) constants were
      similar (11.4+/-1.8 vs. 11.3+/-1.0, p=NS). Equivasodilating doses of
      nitroprusside and 10 microg/kg/min dobutamine decreased pressure-dimension
      stiffness constants after pacing-induced heart failure but not beforehand. The
      aortic wall thickness to diameter ratio was significantly greater in CHF than in
      the control condition (0.30+/-0.08 vs. 0.16+/-0.03, p < 0.01). CONCLUSIONS:
      Aortic compliance is decreased in this model of CHF, and this change is
      attributable primarily to vessel geometry rather than material properties.
      Equivasodilating doses of nitroprusside and equivalent doses of dobutamine
      increase aortic chamber compliance in dogs with CHF, but not in normal dogs.
      These data suggest that the beneficial effects of nitroprusside and dobutamine in
      CHF occur in part from improvement in aortic compliance.

PMID- 9935039
TI  - Increased reactivity of platelets induced by fibrinogen independent of its
      binding to the IIb-IIIa surface glycoprotein: a potential contributor to
      cardiovascular risk.
AB  - OBJECTIVES: To determine whether augmented activation (degranulation) of
      platelets might contribute to the association between higher concentrations of
      fibrinogen and risk of myocardial infarction, we characterized adenosine
      diphosphate (ADP)-induced expression of P-selectin by platelets in whole blood as
      a function of this exposure to selected concentrations of fibrinogen. BACKGROUND:
      An increased risk of myocardial infarction has been associated with increased
      concentrations of fibrinogen. METHODS: Fibrinogen was added to blood
      anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa
      without effect on other coagulation factors). Degranulation of platelets was
      identified by flow cytometry. RESULTS: Addition of fibrinogen to blood did not
      activate platelets under basal conditions (without ADP). By contrast, a
      concentration-dependent increase in ADP and thrombin receptor agonist peptide
      (TRAP)-induced activation occurred with increasing concentrations of fibrinogen.
      Increased ADP-induced degranulation was apparent with the addition of 100 mg/dl
      of fibrinogen (p < or = 0.001 for 1.5 micromol/liter ADP, n=10 subjects).
      Inhibition by abciximab of binding of fibrinogen to the surface glycoprotein IIb
      IIIa did not attenuate the observed augmentation of reactivity induced by
      fibrinogen. Augmented degranulation was associated with uptake of fibrinogen into
      alpha-granules without surface binding despite pretreatment with abciximab as
      shown by laser scanning confocal microscopy. CONCLUSIONS: Fibrinogen in blood
      augments degranulation of platelets in response to ADP and is accompanied by
      uptake of fibrinogen into alpha-granules. Thus, elevated concentrations of
      fibrinogen secondary to inflammation implicated in cardiovascular risk may
      operate, in part, by increasing reactivity of platelets.

PMID- 9935041
TI  - ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with
      cardiovascular disease. American College of Cardiology/American Heart
      Association.

PMID- 9935042
TI  - ACC--50 years of excellence. American College of Cardiology.

PMID- 9935043
TI  - Pulmonary vascular disease in pregnancy.

PMID- 9935044
TI  - Better patency with SK than with tPA?

PMID- 9935046
TI  - Nuclear medicine in the military.

PMID- 9935047
TI  - Donner Laboratory: the birthplace of nuclear medicine.

PMID- 9935045
TI  - Significance of ST-segment elevations in posterior chest leads (V7 to V9) in
      patients with acute inferior myocardial infarction.

PMID- 9935048
TI  - Cardiac 123I-MIBG uptake in idiopathic ventricular tachycardia and fibrillation.
AB  - Patients with idiopathic ventricular tachycardia or fibrillation have no
      additional structural or functional myocardial abnormalities. However, the
      inducibility of typical tachyarrhythmias by physical or mental stress or by
      catecholamine infusion suggests the involvement of the adrenergic system in the
      pathogenesis of these potentially life-threatening diseases. METHODS: 45 patients
      with idiopathic right ventricular outflow tract tachycardia (RVO-VT), 25 patients
      with idiopathic left ventricular tachycardia (ILVT), 15 patients with idiopathic
      ventricular fibrillation (IVF) and 10 age-matched control patients were
      investigated in this study. Diagnoses were made on the basis of detailed
      evaluation of the results of two-dimensional echocardiography, left and right
      ventricular angiography, coronary angiography and endomyocardial biopsy. Local
      presynaptic norepinephrine re-uptake was assessed using the norepinephrine analog
      1231-metaiodobenzylguanidine (MIBG), SPECT and semiquantitative 33-segment bull's
      eye analysis. RESULTS: Locally reduced 123I-MIBG uptake was found in 27 of 45 RVO
      VT patients (60%), 5 of 15 ILVT patients (33%) and 17 of 25 IVF patients (68%).
      Unlike ILVT patients, RVO-VT and IVF patients had significantly reduced segmental
      123I-MIBG uptake of the posterior wall compared with control patients.
      CONCLUSION: Patients with idiopathic tachycardia and fibrillation show abnormal
      1231-MIBG uptake, which indicates presynaptic sympathetic dysfunction. RVO-VT and
      IVF patients exhibit significantly reduced 123I-MIBG uptake in the posterior left
      ventricular wall, whereas ILVT patients do not.

PMID- 9935049
TI  - Cardiac sympathetic nervous system in early essential hypertension assessed by
      123I-MIBG.
AB  - Sympathetic overactivity has been noted in various clinical stages of essential
      hypertension. The purpose of this study is to investigate 123I
      metaiodobenzylguanidine (MIBG) uptake and washout in patients with borderline and
      mild hypertension. METHODS: To assess cardiac sympathetic function in essential
      hypertension, we performed 123I-MIBG cardiac imaging and echocardiography in 25
      normotensive, 25 borderline hypertensive and 24 mildly hypertensive men. Age and
      body mass index were similar in the three groups. RESULTS: Regarding the
      echocardiographic variables, the left ventricular mass index (LVMI) was
      significantly higher in the mildly hypertensive group (125.6+/-28.6 g/m2) than in
      the normotensive (99.9+/-20.7 g/m2) and the borderline hypertensive (110.0+/-24.4
      g/m2) groups (P < 0.001 and P < 0.05, respectively). Regarding the scintigraphic
      variables, the heart-to-mediastinum (H/M) ratio was significantly lower in the
      mildly hypertensive group (1.8+/-0.3) than in the normotensive (2.1+/-0.3) and
      the borderline hypertensive (2.1+/-0.2) groups. In contrast, the washout rate was
      significantly higher in the mildly hypertensive group (17.6%+/-10.8%) than in the
      normotensive (7.0%+/-4.9%) and the borderline (11.9%+/-8.9%) hypertensive groups
      (P< 0.001 and P< 0.02, respectively). In addition, the borderline hypertensive
      group had a significantly higher washout rate than the normotensive group (P <
      0.05). MIBG washout rate had a strong positive correlation with LVMI (r = 0.77, P
      < 0.0001). In contrast, the H/M ratio had a weak negative correlation with LVMI
      (r = -0.40, P < 0.0006). CONCLUSION: During the course of establishment of
      essential hypertension, the washout rate becomes higher with the advance of
      hypertension and with the development of left ventricular hypertrophy. Thus, we
      suggest a strong relationship between cardiac sympathetic activity and the
      advance of hypertension at its early stages.

PMID- 9935050
TI  - Increased brain glucose utilization in Salla disease (free sialic acid storage
      disorder).
AB  - Salla disease is an autosomal recessive lysosomal free sialic acid storage
      disorder characterized by psychomotor retardation and ataxia. MRI studies have
      revealed evidence of dysmyelination, but the biological mechanism of the brain
      dysfunction is unknown. METHODS: Nine patients with Salla disease (age 2.5 mo-42
      y) presenting the disease in varying degrees of severity were studied by PET
      using 2-fluoro-2-deoxy-D-glucose (FDG) as a tracer. Local cerebral metabolic
      rates for glucose (LCMRGlc) in individual brain regions were compared with
      controls. RESULTS: The FDG PET results showed significantly increased LCMRGlc
      values in the frontal and sensorimotor cortex and especially in the basal ganglia
      of the patients. Cerebellar hypometabolism was present in all seven patients with
      marked ataxia, whereas the less severely affected patients without obvious ataxia
      had normal or even high glucose uptake in the cerebellum. CONCLUSION: The
      increased cerebral glucose utilization is a constant finding in Salla disease and
      may reflect the basic defect of the sialic acid metabolism in this disorder. The
      FDG PET findings in the cerebellum suggest a correlation between glucose uptake
      and the severity of the clinical symptoms.

PMID- 9935051
TI  - Regional cerebral blood flow changes in chronic alcoholic patients induced by
      naltrexone challenge during detoxification.
AB  - The recent introduction of the opioid antagonist naltrexone for alcohol
      dependence therapy has been mainly based on behavioral animal models that provide
      evidence of the involvement of the endogenous opioid system in alcohol drinking
      and dependence. However, the neurophysiological mechanisms of the effect of
      naltrexone in alcoholic patients remain unknown. This study investigates the
      effects of a naltrexone challenge on regional cerebral blood flow (rCBF) in
      chronic alcoholic patients during detoxification. METHODS: Sixteen alcoholic
      inpatients underwent two 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain
      SPECTs: a basal SPECT on day 10 of abstinence and a second SPECT on day 12 of
      abstinence after oral administration of 150 mg naltrexone. Region-to-cerebellar
      ratios were obtained for the orbitary frontal, prefrontal, lateral temporal and
      mesial temporal regions, basal ganglia and thalamus in each hemisphere. A
      percentage of rCBF change between both SPECTs was calculated for each region as
      100 x (naltrexone - baseline)/ baseline. Values from 13 brain SPECTs of age
      matched normal volunteers including test-retest measurements were used for
      statistical comparison. RESULTS: In baseline conditions, alcoholics showed lower
      rCBF than controls in left orbitofrontal cortex (84.0+/-5.1 versus 89.8+/-5.0, P
      < 0.01) and prefrontal cortex (left hemisphere: 87.4+/-5.2 versus 96.2+/-3.6, P <
      0.001; right hemisphere: 87.0+/-4.9 versus 95.8+/-4.2, P< 0.001). After
      naltrexone, a significant rCBF decrease was found versus test-retest values in
      left basal ganglia (-3.3%+/-4.0% versus 1.5%+/-4.1%, P< 0.05), right basal
      ganglia (-4.2%+/-4.9% versus 0.6%+/-2.7%, P < 0.01) and left mesial temporal
      region (-4.5%+/-6.8% versus 2.2%+/-2.9%, P < 0.01). CONCLUSION: The rCBF decrease
      detected by SPECT after naltrexone challenge in structures rich in opioid
      receptors, such as the basal ganglia and the left mesial temporal region, may
      reflect a naltrexone-induced decreased metabolic activity in these areas. These
      results support the involvement of the opioid system in alcohol dependence.
      Furthermore, the localization of naltrexone-induced rCBF changes in mesial
      temporal structures and in basal ganglia supports the implication of emotional
      memory and obsessive-compulsive phenomena in craving.

PMID- 9935053
TI  - Factor analysis of dynamic series (FADS) in somatostatin receptor imaging.
AB  - The aim of this article was to study the physiopathology of tumoral uptake of
      111In-pentetreotide using factorial analysis of dynamic series (FADS) and to
      assess the usefulness of this analysis in somatostatin receptor scintigraphy.
      METHODS: Forty-one patients were included, 24 women and 17 men. After intravenous
      injection of 111 MBq 111In-pentetreotide, dynamic image acquisition (68 images of
      30 s) began in front of the suspected tumoral site: thoracic in 10 patients with
      medullary carcinoma of the thyroid and 2 patients with bronchogenic carcinoid,
      and abdominal in 12 cases of midgut carcinoid and 17 cases of other
      gastroenteropancreatic neuroendocrine tumors. FADS was performed with FAMIS
      software. Static images were obtained 4 h and 24 h later. For every patient,
      surgery and/or clinical follow-up (4 y) was used to classify results as true (T)
      or false (F) positive (P) or negative (N) and to evaluate both the sensitivity of
      static images and the usefulness of FADS. RESULTS: Of the 14 cases of carcinoid
      tumor, 5 patients were TN; 9 patients were TP with static images but only 8 were
      TP with FADS (a bronchogenic carcinoid of 6 mm was missed). Of the 17 cases of
      gastroenteropancreatic neuroendocrine tumor, static images were TP in 9 patients,
      and FADS were TP in 5 of these patients (and 4 FN). Static images and FADS were
      FN in 4 patients and TN in 3 patients, and in the 2 last patients static images
      were FP, but FADS were TN. Of the 10 cases of medullary carcinoma of the thyroid,
      static images and FADS were TN in 1 patient, static images were TP in 3 patients
      and FADS were TP in 2 of these patients (and 1 FN). In the six last cases, static
      images were FN, but FADS were FN in 3 patients and TP in 3 patients, showing an
      infiltrate. CONCLUSION: FADS demonstrates that tumoral kinetics are similar to
      those of the spleen. FADS can show a diffuse tumoral uptake corresponding to
      tumoral infiltrate in medullary carcinoma of the thyroid or in hepatic miliaria,
      whereas static images were normal or doubtful.

PMID- 9935052
TI  - Parametric PET imaging of 5HT2A receptor distribution with 18F-setoperone in the
      normal human neocortex.
AB  - Because of 5HT2A receptor's (5HT2AR) putative role in several neuropsychiatric
      diseases, studying it in vivo is an important goal. 18F-setoperone is a well
      validated and widely used PET radioligand for the study of neocortical 5HT2AR. We
      have previously developed and validated in baboons a method to generate
      parametric maps of the binding potential (i.e., the k3-to-k4 ratio) on a pixel-by
      pixel basis, based on a single-dose tracer amount dynamic 18F-setoperone PET
      paradigm, and with the receptor-poor cerebellum as reference structure. However,
      previous semiquantitative PET human studies suggested that nonspecific (NS)
      binding in the neocortex might not be identical to that in the cerebellum.
      METHODS: As a first step in the development of k3:k4 parametric mapping in
      humans, we therefore estimated directly the NS binding of 18F-setoperone in the
      neocortex of four young healthy volunteers who were studied with PET both before
      and after 2 wk of daily therapeutic oral doses of sertindole, an atypical
      neuroleptic possessing strong 5HT2AR antagonistic activity. RESULTS: Visual
      analysis of the dynamic PET data obtained over 120 min confirmed that virtually
      full receptor saturation had indeed been achieved; however, the late neocortical
      time-activity curves (TACs) progressively fell to lower uptake values than
      corresponding cerebellar TACs and could not be fitted according to a four
      compartment (four-Cpt) nonlinear model, indicating lack of specific binding. The
      cerebellum TACs for both the control and the challenge conditions, as well as the
      challenge neocortical TACs, were fitted according to three-Cpt modeling,
      providing the k/k6 ratio and in turn the f2 fraction for both structures. Despite
      the small sample of only four subjects, the f2 fraction for the neocortex was
      significantly larger (i.e., NS binding was smaller) than that estimated for the
      cerebellum. This allowed us to determine the k3-to-k4 ratio for the control
      neocortex using the challenge neocortex as reference structure, that is, without
      using the cerebellum at all. This "assumption-free" approach was also
      successfully used to generate k3:k4 maps for these four subjects, which showed
      highest values for the temporal cortex. CONCLUSION: This study shows that, for
      every new PET or SPECT radioligand and when estimation of specific binding is
      based on a reference structure, it is important to determine the uniformity of
      nonspecific binding before proceeding with human investigations.

PMID- 9935054
TI  - 67Ga scintigraphy in B-cell non-Hodgkin's lymphoma: correlation of 67Ga uptake
      with histology and transferrin receptor expression.
AB  - 67Ga scintigraphy is routinely used in the management of non-Hodgkin's lymphomas
      (NHLs), but the heterogeneity of 67Ga uptake in the different NHL histological
      subtypes has not been clearly explained. The transferrin receptors (TfR/CD71)
      play an important role in the mechanisms of 67Ga uptake by tumor cells. However,
      the relationship between the 67Ga uptake in NHL and the TfR/CD71 expression in
      lymphomatous cells remains to be defined. The aim of this study was to determine
      the intensity of 67Ga uptake in different histological subtypes of B-cell NHL (B
      NHL) and to compare this uptake with the expression of TfR/CD71 on lymphomatous
      cells. METHODS: 67Ga scintigraphy of 47 patients having histologically proven
      lymphomas was investigated. 67Ga uptake was semiquantitatively evaluated in
      regions of interest and was reported as 67Ga uptake index (GaUI). In all cases,
      biopsies were reviewed for classification of NHL. The expression of TfR/CD71 was
      determined on frozen sections and was semiquantitatively evaluated. The
      relationships between GaUI, histology and TfR/CD71 were investigated. RESULTS:
      The values of GaUI were significantly related to the different histological
      subtypes analyzed (P = 0.0007) and to the presence of a large cells component,
      thus demonstrating that 67Ga uptake rose with the grade of lymphoma. Moreover,
      the values of GaUI and TfR/CD71 were closely related in the tested cases (P =
      0.0059). CONCLUSION: There were three factors influencing 67Ga uptake in NHL:
      histology, TfR/CD71 expression and the presence of a large cells component. This
      justifies the usefulness of 67Ga scintigraphy in staging the TfR/CD71-positive
      lymphomas.

PMID- 9935055
TI  - 99mTc-MIBI scintimammography using a dedicated nuclear mammograph.
AB  - This study reports on a prototype single-photon emission mammograph (SPEM)
      dedicated to 99mTc-hexakis-2-methoxyisobutile isonitrile (MIBI)
      scintimammography. Main technical features are reported together with physical
      performance. Preliminary patient data are also reported. METHODS: The SPEM
      detector head is composed of a CsI(T1) scintillating array coupled to a Hamamatsu
      R3292 position-sensitive photomultiplier tube with crossed-wire anode. The high
      resolution collimator is 35-mm thick with a 1.7-mm hole diameter and a 0.2-mm
      septal thickness. The electronic acquisition system is composed of five
      integrated cards with computation based on high-speed programmable
      microprocessors. The readout electronics include correction maps for on-line
      energy correction and spatial uniformity. The small size of the detector head
      allows the use of mechanical breast compression to minimize detection distance
      and tissue scatter. After physical SPEM performance evaluation in vivo
      scintimammography was performed in 29 patients and was compared with a state-of
      the-art Anger camera. RESULTS: The SPEM showed an intrinsic spatial resolution of
      2 mm, an energy resolution of 23% FWHM at 122 keV and spatial uniformities of 18%
      (integral) and 13.5% (differential). The SPEM imaged one 0.4-cm carcinoma missed
      by the Anger camera and resolved as separate lumps an irregular focal uptake on
      the Anger camera image. The remaining cases yielded concordant results.
      CONCLUSION: The SPEM prototype presented in this study shows adequate physical
      characteristics for 99mTc-MIBI scintimammography.

PMID- 9935056
TI  - Overall and single-kidney clearance in children with urinary tract infection and
      damaged kidneys.
AB  - The overall and single-kidney clearance in children with acute urinary tract
      infection was investigated retrospectively using the combination of the relative
      99mTc-dimercaptosuccinic acid (DMSA) uptake and the 51Cr
      ethylenediaminetetraacetic acid clearance. METHODS: There were 180 patients with
      both normal kidneys, 56 with clear unilateral abnormalities on DMSA scintigraphy
      and 11 with two abnormal kidneys. Half of the patients were younger than 2 y, and
      because of the progressive maturation of the renal function, they were not
      considered in the analysis of the absolute overall and single-kidney clearance;
      nevertheless, they were included in the analysis of the relative DMSA percentage
      uptake. RESULTS: When only one kidney was affected on DMSA scintigraphy, the
      clearance of the affected kidney was lower than on the normal side and often
      abnormally low. In these unilaterally affected kidneys, contralateral
      compensation mechanisms tended to occur, resulting in preservation of overall
      clearance. This compensation was probably not present only on the contralateral
      side. On the abnormal side, the clearance was normal in about half of the cases,
      probably because of intrarenal compensation occurring in regions not damaged by
      the infection. In addition to these compensation mechanisms, hyperfiltration was
      probably present in many cases of acute urinary tract infection with intact or
      unilaterally damaged kidneys.

PMID- 9935057
TI  - Quantitative SPECT uptake of 99mTc-dimercaptosuccinic acid by the kidneys in
      children.
AB  - The normal range of values for quantitative SPECT of 99mTc-dimercaptosuccinic
      acid (DMSA) uptake by the kidneys in children was studied. METHODS: Renal
      functioning volume, percentage of injected dose per cubic centimeter of renal
      tissue (%ID/ cm3) and individual kidney uptake of 270 kidneys performed on 135
      children, aged 2 wk-15 y, provided the basic data for this study. The accrual was
      part of the work-up of children with urinary tract infection where no structural
      or functional abnormalities of the renal tract could be established. Children
      were grouped according to age intervals, and a distribution chart was obtained
      with 2 SD above and below the mean of the values obtained for volume (%ID/cm3)
      and kidney uptake in each age group. RESULTS: A significant correlation was found
      between age and functional volume (r = 0.90; 95% confidence interval [CI], 0.88
      0.92; P = 0.000), and a significant inverse correlation was found between age and
      %ID/cm3 (r = -0.86; 95% CI, -0.88 to -0.82; P = 0.000). No statistically
      significant correlation was found between age and kidney uptake (r = -0.20; 95%
      CI, -0.32 to -0.09; P = 0.001). CONCLUSION: It seems that the normal maturational
      changes in renal function observed in infants and newborns do not affect the
      kidney uptake of 99mTC-DMSA. Thus, quantitation of 99mTc-DMSA uptake by the
      kidneys can be used to assess changes in the individual renal function over time
      in this age group.

PMID- 9935058
TI  - Posterior 180 degrees 99mTc-dimercaptosuccinic acid renal SPECT.
AB  - As a result of a high percentage of hypoactive upper poles of kidneys in
      traditional 99mTc-dimercaptosuccinic acid (DMSA) SPECT, a prospective study was
      conducted using 180 degrees acquisition technique compared with 360 degrees to
      minimize tissue attenuation. METHODS: Anterior 180 degrees, posterior 180 degrees
      and 360 degrees renal SPECT images were obtained simultaneously using a dual-head
      camera. Forty-one subjects without renal disease and 16 subjects with 21 cortical
      defects were included in this study. The total counts of the raw data in the
      anterior 180 degrees, posterior 180 degrees and full 360 degrees were calculated.
      Small regions of interest were drawn over the cortex of the kidney on coronal and
      reoriented sagittal slices. Quantitative evaluation of regional activity was
      performed on the same frames in all three acquisition methods. RESULTS:
      Comparison of the total renal counts between the anterior and posterior 180
      degrees data showed reduced counts in the anterior 180 degrees data collection (P
      < 0.01). Visual evaluation of the reconstructed images from anterior 180 degrees,
      posterior 180 degrees and full 360 degrees data collection showed the best image
      uniformity in the posterior 180 degrees image. The upper/lower pole ratio in the
      posterior 180 degrees renal SPECT images increased significantly in comparison to
      full 360 degrees renal SPECT images (P < 0.01) and anterior 180 degrees SPECT
      images (P < 0.01). The renal defects were more clearly visualized in the
      posterior 180 degrees renal SPECT images than the full 360 degrees renal SPECT
      images. The defect/normal cortex ratios in the posterior 180 degrees renal SPECT
      images were much lower than those from the full 360 degrees SPECT images (P <
      0.01) and those from the anterior 180 degrees SPECT images (P < 0.01).
      CONCLUSION: The posterior 180 degrees acquisition technique can avoid the problem
      of hypoactive upper pole and can be less time consuming in 99mTc-DMSA SPECT
      images. It also provides superior lesion contrast in the clinical evaluation of
      patients with renal scarring.

PMID- 9935059
TI  - Quantitative evaluation of salivary gland scintigraphy in Sjorgen's syndrome.
AB  - This study compared the quantitative characteristics of salivary gland
      scintigraphy in patients with Sjogren's syndrome with the histopathologic grading
      of labial biopsy. METHODS: Thirty-nine patients with Sjogren's syndrome were
      studied by salivary gland scintigraphy and labial biopsy. Twelve normal
      volunteers were also studied as a control group for scintigraphic parameters.
      After injection of 370 MBq 99mTc sodium pertechnetate, dynamic salivary
      scintigraphy with lemon juice stimulation was performed for 50 min. Functional
      parameters for the parotid and submandibular glands were calculated, and
      scintigraphic and histopathologic results were compared. RESULTS: With the
      progression of histopathologic grades 1-4, the velocity of tracer secretion
      decreased in the parotid gland (P < 0.05), and the quantity of tracer
      accumulation decreased in the submandibular gland (P < 0.05). The histopathologic
      grade in patients with Sjogren's syndrome was correlated with these scintigraphic
      parameters (P < 0.05): Histopathologic grade = 2.304 - 0.014 x (submandibular
      gland maximum accumulation) + 0.196 x (parotid gland time interval of tracer
      secretion). CONCLUSION: Decreased secretion velocity in the parotid gland and
      decreased accumulation in the submandibular gland were sensitive indicators of
      salivary gland disease in Sjogren's syndrome. The histopathologic grade was
      correlated with these scintigraphic parameters.

PMID- 9935060
TI  - 18F-FDG PET imaging of muscle activity in runners.
AB  - PET with three-dimensional data acquisition using 18F-fluorodeoxyglucose (FDG)
      was applied to evaluate skeletal muscle activity in runners. METHODS: Seven
      healthy adult male volunteers were studied. They ran for a total of 35 min, 15
      min before and 20 min after intravenous injection of FDG. Another 7 adult male
      control subjects were also examined at rest. Images obtained through a set of
      whole-body PET scans were analyzed. Regions of interest (ROIs) were manually
      drawn on images of muscles of both thighs, legs and feet, and the standardized
      uptake ratio (SUR) and total radioactivity distribution (TRD) for each region
      were calculated. RESULTS: The work load was below the anaerobic threshold. SUR of
      foot, leg and thigh were low at rest but during running increased 5.19, 4.30 and
      1.74 times, respectively. The SUR of posterior-to- anterior compartment of the
      leg was 1.1+/-0.1 at rest and 1.6+/-0.5 (P < 0.01) during running. The laterality
      index of both SUR and TRD changed significantly only in the foot of the dominant
      side during running. TRD of the leg, less than half that of the thigh at rest,
      became equivalent to that of the thigh during running. TRD of the foot did not
      change significantly. CONCLUSION: Sole muscles showed highest metabolic
      activation per unit volume during running, which was higher in the dominant side.
      Comparison of whole muscle activity during running indicated the highest
      metabolic activation was in the posterior compartment of the leg, whereas thigh
      muscles showed relatively little changes during running. Our data indicate that
      whole-body FDG PET, especially three-dimensional data acquisition, is a useful
      tool for the investigation of muscular activity during exercise.

PMID- 9935061
TI  - Esophageal scintigraphy with a semisolid meal to evaluate esophageal dysmotility
      in systemic sclerosis and Raynaud's phenomenon.
AB  - Esophageal transit scintigraphy seems to be a valid methodology to assess
      impaired esophageal motility in early stages of disease. The purpose of this
      study was to discriminate patients with primary Raynaud's phenomenon (RP) and
      patients with systemic sclerosis (SSc) from healthy subjects by esophageal
      scintigraphy with a semisolid meal. METHODS: We studied 32 patients with primary
      RP, 18 with SSc and 13 healthy subjects. Dysphagia, acid regurgitation and
      heartburn were scored. After an overnight fast, all subjects underwent esophageal
      scintigraphy, using a semisolid orally ingested bolus (10 mL apple puree) labeled
      with 99mTc-sulfur colloid. Esophageal transit and emptying time and integral
      value were evaluated with the subjects in the upright (sitting) and supine
      positions. Transit time was defined as the time from the entry of 50% of
      radioactivity into the upper esophagus until the clearance of 50% of the bolus
      from the whole esophagus. Emptying time was defined as the time from the entry of
      50% of radioactivity into the upper esophagus, until the clearance of 100% of the
      bolus from the whole esophagus. Integral value was defined as the total counts
      under the time-activity curve normalized to the maximum. RESULTS: Esophageal
      transit and emptying time and integral value, evaluated in both positions, were
      significantly higher in patients with SSc than in healthy subjects and than in
      patients with RP. Moreover, patients with RP had all three parameters, assessed
      in supine position, significantly longer compared to healthy subjects. Clinical
      scores regarding dysphagia, acid regurgitation and heartburn were not
      significantly different between patients with RP and SSc. CONCLUSION: Esophageal
      transit and emptying time and integral value appear to be able to discriminate
      patients with primary RP from patients with SSc and patients with RP from healthy
      subjects, suggesting an early mild esophageal dysfunction in RP.

PMID- 9935062
TI  - Threshold of detection of diffuse lung disease.
AB  - A scintigraphic model of the lungs was used to study the threshold of detection
      of diffuse disease of the lungs. METHODS: Randomly distributed cold lesions of 4,
      8, 12 and 16 mm3 block sizes were created, occupying 0%-50% of lung tissue in
      steps of 1%. These were submitted for reporting to five observers each with a
      normal study for comparison. RESULTS: No observer detected lesions of 4-mm3 block
      size even when up to 50% of the lung was involved. All observers detected lesions
      of 8-mm3 block size when a mean of 27% of lung tissue was involved with lesions.
      As lesion size increased to 12 and 16 mm3, observers detected lesions when a mean
      of 10% and 6% of lung tissue was involved, respectively. Comparison between views
      for each observer showed that the lateral and anterior oblique views were used
      more often than the anterior, posterior oblique and posterior views. CONCLUSION:
      This model suggests that pulmonary scintigraphy has the potential to detect a
      diffuse disease such as emphysema at an early stage of lung involvement. In
      general, small anatomic lesions appear to have more profound scintigraphic
      consequences. However, even scintigraphic lesions of the order of size of the
      pulmonary acinus are easily detected.

PMID- 9935063
TI  - Nuclear medicine in head and neck oncology: reality and perspectives.

PMID- 9935064
TI  - Improved classifications of myocardial bull's-eye scintigrams with computer-based
      decision support system.
AB  - In a recent study, artificial neural networks were trained to detect coronary
      artery disease using scintigraphic data as input. The performance of the networks
      was better than that of human experts using coronary angiography as a gold
      standard. In clinical practice, this type of neural networks will not take over
      the decision-making process from the physician but will assist by proposing an
      interpretation of the scintigram. The purpose of this study was to assess the
      influence of such decision support on the interpretations of the physicians.
      METHODS: A population of 135 patients who had undergone both myocardial 99mTc
      sestamibi rest/stress scintigraphy and coronary angiography within a 3-mo period
      was studied. An image set consisting of the bull's-eye rest, stress, difference
      and quote images was constructed for each patient. Three experienced physicians
      independently classified all image sets regarding the presence and/or absence of
      coronary artery disease in two vascular territories using a four-grade scale. The
      physicians classified the image sets twice with and twice without the advice of
      artificial neural networks. RESULTS: The joint evaluation of the three physicians
      showed significantly improved performance with decision support, measured as
      increases in the areas under the receiver operating characteristic curves from
      0.65 to 0.70 (P = 0.018) and from 0.79 to 0.82 (P = 0.006) for two vascular
      territories. Furthermore, the joint evaluation showed significantly less
      intraobserver and interobserver variability with decision support. CONCLUSION:
      Physicians classifying myocardial bull's-eye images benefit from the advice of
      artificial neural networks. These results show the high potential for neural
      networks as clinical decision support systems.

PMID- 9935065
TI  - Localization of 5-HT1A receptors in the living human brain using [carbonyl
      11C]WAY-100635: PET with anatomic standardization technique.
AB  - Serotonergic 5-hydroxytryptamine-1A (5-HT1A) receptors are of interest in the
      pathophysiology of several neuropsychiatric disorders such as anxiety, depression
      and schizophrenia. [Carbonyl-11C]WAY-100635 has recently been shown to be
      suitable for quantitative determination of 5-HT1A receptors in the human brain
      using PET. For group comparisons of neuroreceptor distribution on a pixel-by
      pixel basis, an anatomic standardization technique is required. In the current
      study, we have built a database of normal 5-HT1A receptor distribution using
      [carbonyl-11C]WAY-100635 and an anatomic standardization technique. METHOD: A PET
      examination lasting 63 min was performed on six subjects after intravenous
      injection of [carbonyl-11C]WAY-100635. The radioactivity of the PET images were
      integrated in the interval 12-63 min and normalized by the radioactivity of the
      cerebellum, providing a measure of the binding potential (BP) in each pixel. Each
      PET image was transformed into a standard brain anatomy using a computerized
      brain atlas system. From the standardized PET images, the sample mean and the SD
      of the BP were calculated in each pixel. RESULT: On the anatomically standardized
      average image, high BP was observed in the cerebral cortices, hippocampus and
      raphe nucleus, whereas low BP was observed in the basal ganglia and thalamus.
      This regional distribution is in good agreement with the distribution of 5-HT1A
      receptors known from in vitro studies. CONCLUSION: The anatomic standardization
      technique permits building of a database of the normal 5-HT1A receptor
      distribution in the living human brain. This technique can be applied for group
      comparisons of neuroreceptor distribution on a pixel-by-pixel basis.

PMID- 9935066
TI  - FDG PET and dual-head gamma camera positron coincidence detection imaging of
      suspected malignancies and brain disorders.
AB  - The purpose of the study was to compare the diagnostic accuracy of
      fluorodeoxyglucose (FDG) images obtained with a dual-head coincidence gamma
      camera (DHC) with those obtained with a dedicated PET in a series of 26 patients.
      METHODS: Nineteen patients with known or suspected malignancies and 7 patients
      with neurological disorders underwent PET imaging after injection of
      approximately 10 mCi of FDG. Whole-body imaging was performed on 19 patients and
      brain imaging on 7 patients. DHC images were then acquired for 30 min over the
      region of interest using a dual-head gamma camera equipped with 3/8-in.-thick
      NaI(TI) crystals and parallel slit-hole collimators. The images were
      reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton
      and Compton/photopeak coincidence events. RESULTS: Although the spatial
      resolutions of PET with a dedicated PET scanner and of DHC are in the same range,
      the lesion detectability remains superior with PET (4 mm for PET versus 13.5 mm
      for DHC in phantom experiments) with a contrast ratio of 5:1. This is most
      probably attributable to the higher sensitivity of PET (2238
      coincidences/min/microCi for PET versus 89 coincidences/min/microCi for DHC). The
      pattern of uptake and interpretation for brain imaging was similar on both PET
      and DHC images in all patients. In the 19 oncology patients, 38 lesions ranging
      from 0.7 to 5 cm were detected by PET. DHC imaging detected 28 (73%) of these
      lesions. Among the 10 lesions not seen with DHC, 5 were less than 1.2 cm, 2 were
      located centrally within the liver and suffered from marked attenuation effects
      and 3 were adjacent to regions with high physiological activity. The
      nondetectability of some lesions with DHC compared with PET can be explained by
      several factors: (a) start of imaging time (mean+/-SD: 73+/-16 min for PET versus
      115+/-68 min for DHC, leading to FDG decay to 6.75 mCi for PET and 5.2 mCi for
      DHC); (b) limited efficiency of a 3/8-inch-thick Nal(TI) crystal to detect 18F
      photons; (c) suboptimal two-dimensional reconstruction algorithm; and (d) absence
      of soft-tissue attenuation correction for centrally located lesions. CONCLUSION:
      FDG DHC imaging is a promising technique for oncological and brain imaging.

PMID- 9935067
TI  - Simultaneous recovery of size and radioactivity concentration of small spheroids
      with PET data.
AB  - Quantification of tumor activity is used to predict prognosis and discriminate
      benign from malignant lesions identified by PET. Accurate quantitation of small
      lesions requires correction for the partial volume effects. Such a correction is
      often based on the recovery coefficient (RC), which depends on the lesion size,
      the object-to-background ratio (OBR) and physical properties of the media. The
      purpose of this investigation was to determine whether a model-based optimization
      method to simultaneously recover the size and the activity concentration of small
      spheroids could improve estimates of lesion radioactivity when object size is
      unknown. For reference, we compared our method with a widely used approach, RC
      correction, that requires the object size to be known. METHODS: A three
      dimensional, spatially varying, object size- and contrast-dependent Gaussian
      model of the point spread function (PSF) of an ECAT EXACT was developed. The
      observed dependence of the PSF on random coincidences and measured
      peak/background activity were included in the PSF using three adjusting factors.
      Size and radioactivity concentration of a spheroid were estimated by adjusting
      size and concentration until model output best matched the image data. Elliptic
      and circular phantoms both containing seven hot spheroids, with OBRs ranging from
      5.6 to 0 background, were evaluated. RESULTS: The proposed quantification method
      reduced the activity error by 11%-63% of the error obtained without correction.
      The greatest error reduction occurred for small spheroids. The average error in
      radius estimation ranged from 2% to 48%, wherein the smallest spheroid produced
      the largest errors. For spheroids with diameters from 8 to 22 mm, Student t test
      (paired, one-tail) showed the proposed method significantly improved accuracy (P
      < 0.05) in comparison with the RC method and also in comparison with optimization
      without the three adjusting factors. CONCLUSION: The model-based optimization
      method improved estimation of radioactivity concentration over that corrected by
      the RC method and that made without any correction. It also provided accurate
      estimation of size for spheroids larger than 6 mm in diameter.

PMID- 9935068
TI  - Thyroid cancer dosimetry using clearance fitting.
AB  - Since 1962, Memorial Sloan Kettering Cancer Center has used an individually
      optimized dosimetry method for patients with thyroid carcinoma undergoing
      radioiodine therapy. This traditional dosimetry method involves a determination
      of the maximum tolerated activity or the activity that will deliver 2 Gy to the
      blood (A(max)), and the corresponding ablative lesion dose (D(lesion)). However,
      the traditional calculations of A(max) and D(lesion) were based on empirical
      assumptions. The objective of this work was to develop a dosimetry method that
      eliminates these assumptions by incorporating patient kinetics and that is not
      restricted to 131I as a tracer and therapeutic agent. METHODS: Patient kinetics
      were incorporated into the dosimetry algorithm by fitting parameters to patient
      clearance measurements. The radioiodines 123I, 124I, 125I and 131I were
      accommodated as tracers and therapeutic agents by incorporating their physical
      half lives and by precalculating photon-absorbed fractions for these
      radionuclides for several thousand patient geometries using Monte Carlo
      simulations. RESULTS: A(max) and D(lesion) have been calculated using the
      traditional and new method for a group of patients, and errors associated with
      each of the above assumptions were examined. Assuming that the initial blood
      activity is distributed instantaneously in 5 L was found to introduce an error in
      A(max) of up to 30%, whereas assuming physical decay beyond the last data point
      introduced an error of up to 50%. CONCLUSION: Individualized fitting of clearance
      data is a practical method to accurately account for inter-patient kinetics
      variations. The substitution of standard kinetics beyond measured data might lead
      to substantial errors in estimating A(max) and D(lesion). In addition, gamma
      camera images, rather than neck probe readings, should be used to determine
      lesion uptakes for thyroid cancer patients.

PMID- 9935069
TI  - Recovery of hepatic asialoglycoprotein receptors after major hepatic resection.
AB  - Although morphological restoration of the hepatic mass after partial hepatectomy
      has been well studied, fewer reports have appeared on the change of functional
      hepatic capacity during liver regeneration. Asialoglycoprotein receptor (ASGP-R)
      is a hepatic cell surface receptor specific for galactose-terminated
      glycoprotein. Kinetic modeling of 99mTc-labeled diethylenetriamine pentaacetic
      acid-galactosyl-human serum albumin (TcGSA) time-activity data yields estimates
      of ASGP-R concentration [R]o and amount R0, which are directly related to
      functional liver mass. We have investigated the changes in ASGP-R status as well
      as liver volume in regenerating human liver after major hepatic resection.
      METHODS: Twenty-two patients (18 noncirrhotic, 4 cirrhotic) had a TcGSA study
      before and 3 wk after major hepatic resection, with a mean hepatic parenchymal
      resection rate of 36.0%. RESULTS: [R]0 was significantly decreased from 0.683+/
      0.024 micromol/L to 0.565+/-0.032 micromol/L (P < 0.001) after resection. The
      decrease in [R]0 was more prominent in cirrhotic patients. Recovery of ASGP-R was
      observed as a significantly increased R0 3 wk after the operation. Subsequent
      (long-term) restoration of ASGP-R appeared to be slower when compared with the
      volume restoration. CONCLUSION: ASGP-R concentration of the liver significantly
      decreased after major hepatic resection. Subsequent recovery of ASGP-R amount was
      shown by TcGSA study. By estimating hepatic functional reserve expressed by ASGP
      R amount and concentration, one may detect a delayed or impaired liver
      regeneration with higher sensitivity.

PMID- 9935070
TI  - 99mTc-tetrofosmin assessment of myocardial perfusion and viability in canine
      models of coronary occlusion and reperfusion.
AB  - The goal of this study was to determine whether 99mTc-tetrofosmin can assess
      regional flow heterogeneity when injected during sustained coronary artery
      occlusion and to estimate the degree of myocardial salvage and viability during
      coronary reperfusion. METHODS: In protocol 1, 99mTc-tetrofosmin, 201 TI and
      microspheres were injected during total left anterior descending (LAD) coronary
      artery occlusion in five anesthetized open-chested dogs. Protocol 2 dogs
      underwent LAD occlusion for either 60 min (n = 7) or 180 min (n = 6) followed by
      105 min of reperfusion. 99mTc-tetrofosmin (10 mCi), 201TI (1 mCi) and
      microspheres were injected 90 min after reflow. In both protocols, myocardial
      99mTc-tetrofosmin and 201TI activities were quantified from regions of interest
      on ex vivo images and by in vitro well counting. RESULTS: In protocol 1, there
      was a linear relationship between 201TI (r = 0.96) and 99mTc-tetrofosmin (r 0.92)
      activities and microsphere flow during the occlusion. In protocol 2, the LAD/left
      circumflex (LCx) defect count ratios for 99mTc-tetrofosmin and 201TI from images
      of myocardial slices were comparable in dogs undergoing either 1 or 3 h of LAD
      occlusion and 105 min of reperfusion. Similarly, the LAD/LCx in vitro count
      ratios were comparable between 201TI and 99mTc-tetrofosmin in 1 and 3 h occluded
      dogs, and significantly lower than the reperfusion flow when these tracers were
      injected. Uptake of both tracers was depressed to a greater extent in areas of
      severe ischemic damage. CONCLUSION: These data suggest that administration of
      99mTc-tetrofosmin during coronary occlusion accurately delineates the flow
      heterogeneity. When given after reperfusion, 99mTc-tetrofosmin uptake was
      significantly reduced in reperfused, infarcted areas and was reflective of
      viability and the degree of myocardial salvage in addition to reperfusion flow.
      These experimental studies validate the clinical use of 99mTc-tetrofosmin for
      assessing persistent coronary artery occlusion, and infarct size and myocardial
      viability after reperfusion.

PMID- 9935071
TI  - Kinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent.
AB  - [99mTc]Technetium[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1] oct-2
      yl]-methyl] (2-mercaptoethyl) amino] ethyl] amino] ethane-thiolato(3-)
      N2,N2',S2,S2']oxo-[1R-(exo-exo)] ([99mTc] TRODAT-1) is a useful imaging agent for
      central nervous system dopamine transporters. The purpose of this study was to
      characterize the in vivo binding potential and kinetic rate constants of this
      agent in nonhuman primates. METHODS: A series of four SPECT scans were performed
      on each of two female baboons with a bolus injection of [99mTc]TRODAT-1 (717+/-78
      MBq; 19.38+/-2.12 mCi). Dynamic images of the brain were acquired over 4 h using
      a triple-head camera equipped with fan-beam collimators. Arterial and venous
      blood were sampled frequently using a peristaltic pump throughout the duration of
      the study. Regions of interest were drawn on the corresponding MRI scan to which
      each functional image was coregistered. Using analytical solutions to the three
      compartment model with the Levenberg-Marquardt minimization technique, each study
      was individually fitted to a kinetic parameter vector (method I). Additionally,
      within each subject, three corresponding intrasubject studies were fitted
      simultaneously to a single parameter vector by constraining the binding
      potential, distribution volume and dissociation rate constant to improve the
      identifiability of the parameter estimates (method II). RESULTS: The results
      clearly indicated that [99mTc] TRODAT-1 localized in the striatum with slower
      washout rate than other brain regions. A maximal target/nontarget ratio of 3.5
      between striatum and cerebellum was obtained. SPECT image analysis of the
      striatum yielded unconstrained k3/k4 values of 3.4+/-1.4, 2.4+/-0.7, 3.0+/-1.5,
      and 4.0+/-10.3, with respective constrained (fixed k4) values of 2.9 +/- 0.4, 2.4
      +/- 0.4, 1.7+/-0.4 and 1.8+/-0.4 in one baboon using method I. With method II,
      the corresponding simultaneously fitted values were 2.1+/-0.3 using no
      constraints and 2.2+/-0.2 using a fixed k4. The second baboon had similar
      results. CONCLUSION: These findings suggest that the binding potential and
      corresponding kinetic rate constants can be reliably estimated in nonhuman
      primates with dynamic SPECT imaging of the dopamine transporter using a
      technetium-based tropane analogue. Furthermore, method II parameter vectors
      compare favorably to those produced using method I based on SEEs.

PMID- 9935072
TI  - Photodegraded nifedipine promotes transferrin-independent gallium uptake by
      cultured tumor cells.
AB  - It was reported previously that normal soft tissues accumulate 67Ga by a
      transferrin-dependent route, but uptake by tumors can be transferrin independent.
      It was also reported that, although overexpression of the transferrin receptor
      can promote Ga avidity, the transferrin-independent uptake of 67Ga is significant
      and can be augmented to exceed transferrin-mediated levels by increasing
      extracellular calcium. In assessing the effect of calcium channel blockers on
      uptake of 67Ga, it was observed that, after exposure to light (either visible or
      ultraviolet [UV]), nifedipine strongly potentiates the cellular uptake of 67Ga by
      a transferrin-independent process. METHODS: The effect of nifedipine on 67Ga
      uptake as a function of time, concentration, duration and type of preexposure to
      light was determined in two cultured Chinese hamster ovary cell lines. One cell
      line lacks the transferrin receptor. In the other, the human transferrin receptor
      has been restored by transfection and is overexpressed constitutively. RESULTS:
      Although there are some differences in pattern of stimulation of uptake,
      nifedipine subjected to either UV or fluorescent light strongly promotes the
      uptake of 67Ga in the cultured cells in a time-dependent and concentration
      dependent manner. Maximal uptake of 67Ga occurs when the cells are incubated for
      30 min with 25 micromol/L nifedipine preexposed to either 4h of fluorescent or 1h
      of UV light. Under these conditions, uptake of 67Ga is 1000-fold greater than
      basal levels and 50-fold greater than can be achieved by the transferrin
      dependent route. Light-shielded nifedipine has no effect on 67Ga uptake.
      CONCLUSION: The effect of photodegraded nifedipine on the uptake of 67Ga is
      independent of expression of the transferrin receptor. The potential for
      photodegraded nifedipine to improve oncologic imaging with 67Ga warrants further
      investigation.

PMID- 9935073
TI  - Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized
      anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry.
AB  - The alpha-particle-emitting radionuclides have several physical characteristics
      that make them attractive candidates for radioimmunotherapy: (a) high linear
      energy transfer; (b) short path lengths (50-80 microm); and (c) limited ability
      of cells to repair damage to DNA. This article describes the pharmacokinetic,
      bioactivity, toxicity and chemical characteristics of alpha-particle-emitting,
      213Bi and 212Bi radiometal conjugated HuM195 (anti-CD33) constructs. Conjugation
      of HuM195 to SCN-CHX-A-DTPA resulted in the attachment of up to 10 chelating
      ligand molecules per antibody. RESULTS: Radiolabeling efficiency of the CHX-A
      DTPA-HuM195 construct with 213Bi was 78%+/-10% (n = 46) after 10 min at specific
      activities of up to 1110 MBq/mg. The immunoreactivity of the 213Bi-labeled CHX-A
      DTPA-HuM195 construct was 84%+/-10% (n = 28) and was independent of the specific
      activity. The bismuth-labeled CHX-A-DTPA-HuM195 construct was rapidly
      internalized into the cell in a time-dependent manner ranging from 50% at 1 h to
      65% at 24 h. 205Bi/206Bi-labeled constructs were stable for at least 2 d in vitro
      in the presence of human serum at 37 degrees C. After injection into mice, there
      was no uptake or loss of bismuth to mouse tissues, which do not express CD33, or
      to the kidney, which has avidity for free bismuth. Mice injected
      intraperitoneally with doses of (213Bi)CHX-A-DTPA-HuM1 95 ranging from 18.5 to
      740 MBq/kg showed no toxicity, but at 2590 MBq/kg, two of the three mice died
      within 2 wk and a third mouse showed significant reductions in white blood cell
      counts. Mice injected intravenously with doses of (213Bi)CHX-A-DTPA-HuM195 up to
      370 MBq/kg exhibited little toxicity, but 666 MBq/kg was above the MTD for mice.
      Leukemia cell killing in vitro with bismuth-labeled HuM1 95 showed dose- and
      specific activity-dependent killing of CD33+ HL60 cells; approximately 50%
      killing was observed when two bismuth atoms (50 fM radiolabeled antibody) were
      initially bound onto the target cell surface. CONCLUSION: Alpha-emitting
      antibodies are among the most potent cytotoxic agents known, yet are specific and
      appear safe in vivo. The physical and biochemical characteristics of the 213Bi
      isotope and its generation, as well as the biochemistry of the 213Bi-labeled CHX
      A-DTPA-HuM195 construct, make it possible to use the constructs safely and
      feasibly in humans at therapeutic levels.

PMID- 9935074
TI  - Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model.
AB  - We have evaluated Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM), an
      effective marker for the delineation of hypoxic but viable tissue, in vitro in
      the EMT6 carcinoma cell line under varying degrees of hypoxia and compared it
      with the flow tracer 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM)
      and the hypoxic tracer 18F-fluoromisonidazole (MISO). We have also compared the
      uptake of Cu-ATSM and Cu-PTSM in vivo and ex vivo in a murine animal model
      bearing the EMT6 tumor. METHODS: Uptake of 64Cu-ATSM, 64Cu-PTSM and 18F-MISO in
      vitro into EMT6 cells was investigated at the dissolved oxygen concentrations of
      0, 1 x 10(3), 5 x 10(3), 5 x 10(4) and 2 x 10(5) ppm. Biodistribution performed
      at 1, 5, 10, 20 and 40 min compared 64Cu-ATSM with 64Cu-PTSM in BALB/c mice
      bearing EMT6 tumors. To determine long-term retention of 64Cu-ATSM,
      biodistribution was also performed at 1, 2 and 4 h. Ex vivo autoradiography of
      tumor slices after co-injection of 60Cu-PTSM (60Cu, T1/2 = 23.7 min) and 64Cu
      ATSM (64Cu, t1/2 = 12.7 h) into the same animal was performed. RESULTS: After 1
      h, 64Cu-ATSM was taken up by EMT6 cells: 90% at 0 ppm, 77% at 1 x 10(3) ppm, 38%
      at 5 x 10(3) ppm, 35% at 5 x 10(4) ppm and 31% at 2 x 10(5) ppm. 18F-MISO also
      showed oxygen concentration dependent uptake, but with lower percentages than
      64Cu-ATSM. 64Cu-PTSM showed 83%-85% uptake into the cells after 1 h, independent
      of oxygen concentration. Biodistribution data of 64Cu-ATSM and 64Cu-PTSM showed
      optimal tumor uptake after 5 and 10 min, respectively (0.76% injected dose
      (ID)/organ for 64Cu-ATSM and 1.11%ID/organ for 64Cu-PTSM). Ex vivo imaging
      experiments showed 60Cu-PTSM uniform throughout the EMT6 tumor, but heterogeneous
      uptake of 64Cu-ATSM, indicative of selective trapping of 64Cu-ATSM into the
      hypoxic tumor cells. CONCLUSION: Cu-ATSM exhibits selectivity for hypoxic tumor
      tissue both in vivo and in vitro and may provide a successful diagnostic modality
      for the detection of tumor ischemia.

PMID- 9935075
TI  - Imaging of apoptosis (programmed cell death) with 99mTc annexin V.
AB  - Apoptosis (programmed cell death) is a critical element in normal physiology and
      in many disease processes. Phosphatidylserine (PS), one component of cell
      membrane phospholipids, is normally confined to the inner leaflet of the plasma
      membrane. Early in the course of apoptosis, this phospholipid is rapidly exposed
      on the cell's outer surface. Annexin V, an endogenous human protein, has a high
      affinity for membrane-bound PS. This protein has been labeled with fluorescein
      and has been used to detect apoptosis in vitro. We describe the use of
      radiolabeled annexin V to detect apoptosis in vivo. The results are compared to
      histologic and flow cytometric methods to identify cells and tissues undergoing
      apoptosis. METHODS: Annexin V was coupled to hydrazinonicotinamide (HYNIC) and
      radiolabeled with 99mTc. Bioreactivity of 99mTc-HYNIC annexin V was compared with
      fluorescein isothiocyanate (FITC)-labeled annexin V in cultures of Jurkat T-cell
      lymphoblasts and in ex vivo thymic cell suspensions undergoing apoptosis in
      response to different stimuli. In addition, the uptake of FITC annexin V and
      99mTc-HYNIC annexin V was studied in heat-treated necrotic Jurkat T-cell
      cultures. In vivo localization of annexin V was studied in Balb/c mice injected
      with 99mTc-HYNIC annexin V before and after induction of Fas-mediated hepatocyte
      apoptosis with intravenously administered antiFas antibody. RESULTS: Membrane
      bound radiolabeled annexin V activity linearly correlated to total fluorescence
      as observed by FITC annexin V flow cytometry in Jurkat T-cell cultures induced to
      undergo apoptosis in response to growth factor deprivation (N = 10, r2 = 0.987),
      antiFas antibody (N = 8, r2 = 0.836) and doxorubicin (N = 10, r2 = 0.804); and in
      ex vivo experiments on thymic cell suspensions with dexamethasone-induced
      apoptosis from Balb/c mice (N = 6, r2 = 0.989). Necrotic Jurkat T-cell cultures
      also demonstrated marked increases in radiopharmaceutical (4000-5000-fold) above
      control values. AntiFas antibody-treated Balb/c mice (N = 6) demonstrated a three
      fold rise in hepatic uptake of annexin V (P < 0.0005) above control (N = 10),
      identified both by imaging and scintillation well counting. The increase in
      hepatic uptake in antiFas antibody-treated mice correlated to histologic evidence
      of fulminant hepatic apoptosis. CONCLUSION: These data suggest that 99mTc-HYNIC
      annexin V can be used to image apoptotic and necrotic cell death in vivo.

PMID- 9935076
TI  - A novel method to label liposomes with 99mTc by the hydrazino nicotinyl
      derivative.
AB  - In this study a new 99mTc labeling method for polyethyleneglycol (PEG)-coated
      liposomes is described. The in vitro and in vivo characteristics were compared
      with the conventional 99mTc-HMPAO-labeled PEG-coated liposomes. METHODS: PEG
      coated liposomes were labeled with 99mTc by the hydrazino nicotinyl (HYNIC)
      derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG
      coated liposomes labeled with 99mTc-HMPAO. In vitro stability tests were
      performed. Biodistribution and imaging characteristics of both liposomal
      preparations were determined in rats with Staphylococcus aureus infection in the
      left calf muscle. RESULTS: Per liposome, 230 hydrazine groups were incorporated.
      The labeling efficiency of the 99mTc-HYNIC liposomes was greater than 95%, so no
      postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes.
      The 99mTc-HYNIC liposomes showed greater in vitro stability than the conventional
      99mTc-HMPAO liposomes. Abscess uptake of the 99mTc-HYNIC liposomes was
      significantly greater (1.74+/-0.38%ID/g versus 1.26+/-0.29%ID/g, 24 h
      postinjection, P < 0.03). Furthermore, kidney uptake of the 99mTc-HYNIC liposomes
      was one third of the uptake of the 99mTc-HMPAO liposomes (0.79+/-0.07%ID/g versus
      2.47+/-0.35%ID/g, 24 h postinjection, P < 0.0001). CONCLUSION: This new 99mTc
      HYNIC-based labeling method for liposomes is rapid, efficient and easy to
      perform. Most importantly, the 99mTc-labeled liposomes have an improved stability
      and in vivo characteristics. The new labeling method is a major step forward
      toward a radiopharmaceutical for infection imaging that can be prepared in a one
      step procedure within 15 min at room temperature and thus can be applied in every
      routine clinical practice.

PMID- 9935077
TI  - Bispecific antibody and bivalent hapten radioimmunotherapy in CEA-producing
      medullary thyroid cancer xenograft.
AB  - The purpose of this study was to compare the toxicity and efficacy of two-step
      radioimmunotherapy using a bispecific anticarcinoembryonic antigen (CEA)/anti
      diethylenetriamine pentaacetic acid (DTPA) antibody (F6-734 bispecific monoclonal
      antibodies (BsMAbs) and an 131I-di-DTPA-TL bivalent hapten with F(ab')2 fragments
      of the same directly labeled anti-CEA 131-F6. METHODS: Eight groups of nude mice
      subcutaneously grafted with the human TT medullary thyroid cancer cell line were
      injected once tumor volume reached about 200 mm3. Two groups received 37 or 92.5
      MBq (1 or 2 nmol) 131I-di-DTPA-TL 48 h after injection of 2 or 4 nmol F6-734
      BsMAb and two groups received 37 or 92.5 MBq (250 microg) 131I-F6. Four control
      groups were treated respectively with (a) 92.5 MBq nonspecific 131I-734
      fragments, (b) 92.5 MBq 131I-di-DTPA-TL 48 h after injection of a mixture of
      irrelevant F6-679 (anti-CEA/anti-histamine) and G7A5-734 (anti-melanoma/anti
      DTPA) BsMAb, (c) 250 microg nonradiolabeled F6, and 250 microg F6-734 BsMAb and
      then 48 h later 1.25 nmol of nonradiolabeled hapten. A control group received no
      injections. Toxicity was evaluated by determining animal weight and the number of
      leukocytes and platelets, and efficacy by variation in tumor volume and
      thyrocalcitonin during a 90-d period. Histological analysis of tumors and
      statistical studies were performed. RESULTS: The time required for the tumor to
      double in size was respectively 57 and 86 d with 37 and 92.5 MBq F6-734/131I-di
      DTPA-TL and 44 and 65 d with 37 and 92.5 MBq 131I-F6. Changes in thyrocalcitonin
      levels were parallel to those in tumor volume. Weight loss was 5%, leukocyte
      nadirs respectively 1640+/-838 and 1560+/-1160/mm3 and platelet nadirs 1.46+/
      0.52 10(6)/mm3 and 0.73+/-0.38 10(6)/mm3 after injections of 37 and 92.5 MBq F6
      734/1311-di-DTPA-TL. Weight loss was respectively 8% and 16%, leukocyte nadirs
      50+/-100/mm3 and 175+/-50/mm3 and platelet nadirs 0.71+/-0.18 10(6)/mm3 and
      0.48+/-0.11 10(6)/mm3 after injections of 37 and 92.5 MBq 131I-F6. CONCLUSION:
      Two-step radioimmunotherapy was as efficient as the one-step system and markedly
      less toxic.

PMID- 9935078
TI  - Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor
      imaging.
AB  - The aim of the study was to develop a simple 18F-labeled amino acid as a PET
      tracer for cerebral and peripheral tumors. O-(2-[18F]fluoroethyl)-L-tyrosine (L
      [18F]FET) was synthesized and biologically evaluated. Results of the first human
      PET study are reported. METHODS: No carrier added (n.c.a.) and D-[18F]FET were
      prepared by 18F-fluoroethylation of L- and D-tyrosine in a two-step procedure.
      Biodistribution studies were performed in mice. The metabolic fate of L-[18F]FET
      was investigated in plasma, brain, tumor and pancreatic tissue samples using
      chromatographic procedures. Tumor uptake studies were performed in mammary
      carcinoma-bearing mice and in mice with the colon carcinoma SW 707. In a human
      PET study, a 59-y-old man with a recurrent astrocytoma was imaged using n.c.a. L
      [18F]FET. RESULTS: Synthesis of [18F]FET was accomplished in about 50 min with an
      overall radiochemical yield of 40%. The uptake of L-[18F]FET in the brain of mice
      reached a level >2% ID/g between 30 and 60 min postinjection. The brain uptake of
      the D-isomer was negligible, indicating blood-brain barrier penetration by a
      specific amino acid transport system. L-[18F]FET is not incorporated into
      proteins. High-performance liquid chromatography (HPLC) analysis of brain,
      pancreas and tumor homogenates as well as plasma samples of mice at 10, 40 or 60
      min postinjection showed only unchanged L-[18F]FET. Activity uptake in the bone
      did not exceed 2% ID/g at 40 min postinjection. The brain uptake of L-[18F]FET in
      mice bearing mammary carcinomas and colon carcinomas reached 7.1%+/-1.2% ID/g and
      6.4%+/-1.7% ID/g 1h postinjection, respectively. In the first human study, L
      [18F]FET-PET allowed a clear delineation of a recurrent astrocytoma. Thirty-five
      minutes postinjection, the tumor-to-cortex ratio was >2.7. A tumor-to-blood ratio
      >1.5 was reached at 30 min postinjection and continued to increase. No
      significant activity accumulation was observed in peripheral organs after
      approximately 40 min postinjection. CONCLUSION: The high in vivo stability of L
      [18F]FET, its fast brain and tumor uptake kinetics, its low accumulation in
      nontumor tissue and its ease of synthesis strongly support further evaluation of
      L-[18F]FET as an amino acid tracer for cerebral and peripheral tumors.

PMID- 9935080
TI  - Moyamoya disease and pregnancy.

PMID- 9935079
TI  - What can fatty acids add in LBBB and to the myocardial viability issue?

PMID- 9935081
TI  - Retreatment of Graves' disease with radioiodine 131I.

PMID- 9935082
TI  - The MIRD perspective 1999. Medical Internal Radiation Dose Committee.
AB  - The MIRD schema is a general approach for medical internal radiation dosimetry.
      Although the schema has traditionally been used for organ dosimetry, it is also
      applicable to dosimetry at the suborgan, voxel, multicellular and cellular
      levels. The MIRD pamphlets that follow in this issue and in coming issues, as
      well as the recent monograph on cellular dosimetry, demonstrate the flexibility
      of this approach. Furthermore, these pamphlets provide new tools for radionuclide
      dosimetry applications, including the dynamic bladder model, S values for small
      structures within the brain (i.e., suborgan dosimetry), voxel S values for
      constructing three-dimensional dose distributions and dose-volume histograms and
      techniques for acquiring quantitative distribution and pharmacokinetic data.

PMID- 9935083
TI  - MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions-
      radionuclide S values at the voxel level. Medical Internal Radiation Dose
      Committee.
AB  - The availability of quantitative three-dimensional in vivo data on radionuclide
      distributions within the body makes it possible to calculate the corresponding
      nonuniform distribution of radiation absorbed dose in body organs and tissues.
      This pamphlet emphasizes the utility of the MIRD schema for such calculations
      through the use of radionuclide S values defined at the voxel level. The use of
      both dose point-kernels and Monte Carlo simulation methods is also discussed. PET
      and SPECT imaging can provide quantitative activity data in voxels of several
      millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained
      using present imaging technology. For submillimeter dimensions, autoradiographic
      methods may be used when tissues are obtained through biopsy or autopsy. Sample S
      value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm
      on edge are given in the appendices to this pamphlet. These S values may be used
      to construct three-dimensional dose profiles for nonuniform distributions of
      radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data
      are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two
      examples illustrating the use of voxel S values are given, followed by a
      discussion of the use of three-dimensional dose distributions in understanding
      and predicting biologic response.

PMID- 9935084
TI  - Periorbital rejuvenation: a review of dermatologic treatments.
AB  - BACKGROUND: The periorbital region serves as a barometer of chronologic and
      environmental age and, as such, patients often seek its cosmetic rejuvenation.
      OBJECTIVE: The purpose of this article was to review the dermatologic treatments
      available for periorbital skin rejuvenation. METHODS: Topical retinoic and
      glycolic acid preparations, chemical peels, botulinum and collagen injections,
      dermabrasion, and laser resurfacing procedures for periorbital skin rejuvenation
      were reviewed. The relative benefits and risks of each treatment were detailed.
      RESULTS: Minimal photodamage with mild rhytides should be responsible to topical
      acid therapy and superficial peels, whereas moderate wrinkling and photodamage
      generally require medium-depth peels, collagen injections, or erbium:YAG laser
      resurfacing. Deeper rhytides and more extensive cutaneous photo-damage usually
      necessitate CO2 laser resurfacing and botulinum injections. CONCLUSIONS: Proper
      patient selection and assessment of aging severity are critical to determine the
      best therapeutic option.

PMID- 9935085
TI  - Comparison of the Q-switched alexandrite, Nd:YAG, and ruby lasers in treating
      blue-black tattoos.
AB  - BACKGROUND: A new generation of highly selective short-pulsed lasers has emerged
      in recent years for the treatment of tattoos. Several studies (including reports
      by the present investigators) have proven the efficacy of each of the three
      commercially available, FDA approved devices; namely, the Q-switched alexandrite,
      Q-switched Nd:YAG and Q-switched ruby lasers. Considerable differences among the
      three have been reported in relation to the rate of clearing of the tattoo ink
      particles, tissue effects, beam profile, wound healing, and side effects.
      OBJECTIVE: This study was primarily conducted to examine and compare the clinical
      response of patients with blue-black tattoos simultaneously treated with three
      different Q-switched lasers (alexandrite, Nd:YAG, ruby) with a focus on the
      percentage of tattoo lightening/clearance and the occurrence or non-occurrence of
      pigmentary change as a side effect. METHODS: A total of forty-two blue-black
      tattoos seen at two laser centers (Massachusetts General Hospital Dermatology
      Laser Center and Laser and Skin Surgery Center of La Jolla) were simultaneously
      treated with three types of Q-switched lasers: a Candela Q-switched alexandrite
      laser (755nm 50-100 nanoseconds, 3.0 mm spot size, 6-8 J/cm2); a Continuum
      Biomedical Q-switched Nd:YAG laser (1064nm, 10-20 nanoseconds, 3.0 mm spot size,
      5-10 J/cm2); and a Spectrum Q-switched ruby laser (694 nm, 25-40 nanoseconds, 5.0
      mm spot size, 4-10 J/cm2). Paired t-tests and McNemar tests were used to compare
      the treatment outcome and pigmentation side effects between sites per tattoo,
      with each site representative of one of the three lasers. The statistical
      significance level was set at p < .05. RESULTS: Overall, the Q-switched ruby
      laser had a significant difference in tattoo lightening versus the Q-switched
      Nd:YAG and Q-switched alexandrite lasers. An increase in the number of treatments
      paralleled a statistically significant increase in tattoo clearance for all three
      Q-switched lasers. CONCLUSION: The Q-switched ruby laser had the highest
      clearance rate in blue-black tattoos and the highest incidence of long-lasting
      hypopigmentation. The Nd:YAG had no incidence of hypopigmentation.

PMID- 9935086
TI  - Effect of pretreatment on the incidence of hyperpigmentation following cutaneous
      CO2 laser resurfacing.
AB  - BACKGROUND: Transient hyperpigmentation is the most common complication seen
      following cutaneous carbon dioxide (CO2) laser resurfacing. OBJECTIVE: The
      purpose of this study was to determine whether the use of a topical skin
      lightening regimen prior to cutaneous laser resurfacing reduces the incidence of
      post-laser resurfacing hyperpigmentation. METHODS: One hundred consecutive CO2
      laser resurfacing patients (skin types I-III) were randomized to receive
      preoperative treatment with 10% glycolic acid cream twice daily (n=25),
      hydroquinone 4% cream qHS and tretinoin 0.025% cream twice daily (n=25) or no
      pretreatment (n=50, control) for at least 2 weeks. Clinical and photographic
      assessments were performed prior to laser resurfacing and at 4 and 12 weeks
      following treatment. RESULTS: There was no significant difference in the
      incidence of post-CO2 laser resurfacing hyperpigmentation between subjects who
      received pretreatment with either topical glycolic acid cream or combination
      tretinoin/hydroquinone creams and those who received no pretreatment regimen.
      CONCLUSION: It is postulated that reepithelialization after cutaneous laser
      resurfacing includes follicular melanocytes that have not been affected by
      topical pretreatment. When instituted as a component of the skin care regimen
      postoperatively, topical hydroquinone, tretinoin and/or glycolic acid
      preparations may be helpful in reducing post-laser resurfacing hyperpigmentation.

PMID- 9935087
TI  - The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic
      groups.
AB  - BACKGROUND: There is a dearth of published data regarding chemical peels in
      darker racial-ethnic groups. OBJECTIVE: The purpose of the present investigation
      was to assess the clinical efficacy and safety of a new superficial salicylic
      acid peel in individuals of skin types V and VI. METHODS: Twenty-five patients
      were included in this pilot investigation. Nine had acne vulgaris, 5 had post
      inflammatory hyperpigmentation, 6 had melasma, and 5 had rough, oily skin with
      enlarged pores. The patients were pre-treated for 2 weeks with hydroquinone 4%
      prior to undergoing a series of five salicylic acid chemical peels. The
      concentrations of salicylic acid were 20% and 30%. The peels were performed at 2
      week intervals. RESULTS. Moderate to significant improvement was observed in 88%
      of the patients. Minimal to mild side effects occurred in 16%. CONCLUSION: The
      results of this study suggest that superficial salicylic acid peels are both safe
      and efficacious for treatment of acne vulgaris, oily skin, textural changes,
      melasma, and post-inflammatory hyperpigmentation in patients with skin types V
      and VI.

PMID- 9935088
TI  - Merkel cell carcinoma: spontaneous resolution and management of metastatic
      disease.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous
      neoplasm. The primary form of initial treatment is wide surgical excision. The
      use of Mohs micrographic surgery as the primary form of treatment in MCC has been
      controversial. The course of MCC is often aggressive, with early metastasis,
      widespread disease, and death. Despite the poor prognosis, spontaneous regression
      has occasionally been reported. OBJECTIVE: We describe the clinical course of two
      patients with Merkel cell carcinoma who underwent treatment with Mohs
      micrographic surgery for the primary MCC. Metastases were excised in the first
      case and spontaneously regressed in the second. Both patients are without
      clinical disease at the time of this report. METHODS: Histopathology, clinical
      records, and the current literature are reviewed. RESULTS: One patients was
      without recurrence of MCC for 13 years of follow-up. The other patient
      experienced clinical spontaneous remission after nodal spread of the disease,
      with no recurrence for 18 months after clinical remission and 24 months after
      surgery. CONCLUSION: The treatment of Merkel cell carcinoma with Mohs
      micrographic surgery (MMS) has been successful for the control of primary skin
      disease, and is at least comparable to wide excision. Spontaneous regression may
      occur in the course of this usually relentless and aggressive disease. The
      explanation for spontaneous regression of MCC is unknown.

PMID- 9935089
TI  - Viability of isolated single hair follicles preserved at 4 degrees C.
AB  - BACKGROUND: Hair follicle preservation for the purpose of delayed application
      would help us to transplant hair follicles more efficiently. METHODS: Isolated
      single hair follicles were preserved at 4 degrees C in four different solutions.
      Viability of preserved follicles was judged by organ culture and cell culture. In
      addition, a small number of hair follicles were transplanted into athymic mice.
      RESULTS. By cell culture, both dermal papilla and outer root sheath cells could
      be cultivated after 7 days of preservation. Hair follicles preserved for 48 hours
      showed a significant increase of hair shafts in organ culture. Those preserved
      for 7 days regrew well when transplanted into athymic mice. CONCLUSION:
      Preservation of hair follicles at 4 degrees C could be one option to prepare many
      follicular units at one time for transplantation.

PMID- 9935090
TI  - Scalp extension--a quantitative study.
AB  - The authors have compared the results of scalp reductions with extenders with
      their earlier results of scalp reductions without extenders. The extenders seem
      to prevent "stretch-back" and provide 30 to 86% more effectiveness when a second
      reduction is performed 4 weeks later.

PMID- 9935092
TI  - Long cotton wool rolls as compression enhancers in macrosclerotherapy for
      varicose veins.
AB  - BACKGROUND: Macrosclerotherapy in combination with compression has proven to be
      safe and effective in the treatment of varicose veins. Local compression is
      increased by pads, according to Laplace law. Firm rolls of cotton wool are fixed
      over the course of the entire vein to increase local compression and to reduce
      complications. Additional compression is given by a combination of a class I
      (daytime and nighttime) and class II (daytime only) medical compression hosiery.
      PURPOSE: To evaluate the effectiveness and side effects of sclerocompression
      therapy with cotton wool rolls in combination with medical compression hosiery.
      METHOD: Prospective study with 100 patients (120 legs) with primary varicose
      veins, which are treated with polidocanol as sclerosant with the empty vein
      technique. Immediately after the injection, a long cotton wool roll is placed
      over the entire vein and fixed. Additional compression is obtained with class I
      and class II medical compression hosiery. The interface pressure on the skin,
      just under the cotton wool roll, is measured on 12 legs with the aid of an
      interface pressure measuring instrument (Oxford Pressure Monitor). RESULTS: Good
      sclerosing results are obtained in all patients. Side effects are classified as
      early and late. In 16 patients, minor side effects which needed no treatment are
      observed. In only 3 cases (2.5%), intravascular blood clots (2) and phlebitis (1)
      needed incision and expression. The mean interface pressure of all measuring
      sensors under the cotton wool roll is 84 mm/Hg (68 to 122 mm/Hg). CONCLUSION:
      This study proves the high effectiveness of a cotton wool roll compression right
      at the place of treatment. By using these long cotton wool compression rolls, the
      compression part of sclerocompression therapy becomes more effective and much
      easier to perform.

PMID- 9935091
TI  - Recalcitrant scarring follicular disorders treated by laser-assisted hair
      removal: a preliminary report.
AB  - BACKGROUND: Recalcitrant scarring follicular disorders have been treated
      previously by removing hair follicles both surgically by scalp resection with
      skin grafting and with X-ray epilation. Laser-assisted hair removal may provide
      an alternate method of hair removal with less associated morbidity. OBJECTIVE:
      The goal is to determine whether laser-assisted hair removal can be used to treat
      follicular inflammatory disorders by destroying hair follicles. METHODS: Three
      patients with various scarring follicular disorders (dissecting cellulitis of the
      scalp, keratosis pilaris spinulosa decalvans, and pseudofolliculitis barbae) were
      treated with the long-pulse non-Q-switched ruby laser and followed clinically.
      RESULTS: The patients tolerated the treatments well without significant side
      effects and noted improvement of their condition along with decreased hair growth
      in the treated area. CONCLUSION: Laser-assisted hair removal may provide a safe,
      effective means of treating recalcitrant follicular disorders.

PMID- 9935093
TI  - The use of the 1.0 mm handpiece in high energy, pulsed CO2 laser destruction of
      facial adnexal tumors.
AB  - BACKGROUND: The treatment of syringoma and trichoepithelioma has included punch
      and shave biopsy, excision, electrodessication, as well as continuous wave and
      superpulsed carbon dioxide laser ablation. More recently, high-energy pulsed CO2
      lasers have been reported to be effective with standard available handpieces that
      deliver collimated beams. OBJECTIVE: To report our experience using a focusing
      handpiece (1.0 mm spot at focus) with a high energy pulsed CO2 laser. METHODS:
      Four patients with syringoma and two with multiple trichoepithelioma were treated
      with a high energy pulsed CO2 laser using a 1 mm spot size focusing handpiece.
      Pulse energies ranged from 125 to 250 mJ. All patients were followed 2 weeks
      after treatment and then for variable periods ranging from 8 to 18 months
      (mean=13.3 months). RESULTS: The 1 mm spot focusing handpiece permitted rapid
      tumor ablation with optimal matching of lesion size and laser spot diameter.
      Recurrence of tumor was associated with superficial ablation while complications
      such as hypopigmentation and atrophy were associated with deeper ablation.
      CONCLUSION: Facial adnexal tumors such as syringoma and trichoepithelioma can be
      successfully treated with the 1.0 mm handpiece in tandem with high energy pulsed
      CO2 lasers.

PMID- 9935095
TI  - Calcifying basal cell carcinomas.
AB  - BACKGROUND: Dystrophic calcification refers to calcium deposition occurring in
      association with local tissue injury or abnormality. Little is known about
      dystrophic calcification occurring in malignant cutaneous neoplasms. OBJECTIVE:
      The purpose of this study was to determine the frequency and pattern of
      dystrophic calcification occurring in basal cell carcinomas and squamous cell
      carcinomas. METHODS: Consecutive cases (200) of basal cell carcinoma and squamous
      cell carcinoma were reviewed for evidence of dystrophic calcification. Histologic
      subtype, location of calcification, and tumor site were noted. RESULTS: Of 200
      basal cell carcinomas, 41 (21%) showed evidence of dystrophic calcification,
      compared with 6 (3%) squamous cell carcinomas. Calcifying basal cell carcinomas
      were more likely to have a more aggressive histologic subtype and to be located
      on the trunk. CONCLUSION: Skin calcium binding protein may be responsible for the
      calcium deposition and account for the discrepancy seen between the frequency of
      calcification occurring in basal cell carcinomas and squamous cell carcinomas. As
      with other tumors with follicular differentiation, calcium deposits were located
      in keratin-filled cysts. This pattern of dystrophic calcification may be a marker
      of follicular differentiation.

PMID- 9935094
TI  - Giant malignant eccrine spiradenoma of the scalp.

PMID- 9935096
TI  - Laser therapy of spider leg veins: clinical evaluation of a new long pulsed
      alexandrite laser.
AB  - BACKGROUND: The response of spider leg veins to laser or intense pulsed light
      therapy has generally been characterized by varying degrees of success and
      frequently inconsistent clinical response rates. OBJECTIVE: The purpose of this
      study was to examine the effectiveness of the 755 nm long pulsed infrared
      alexandrite (LPA) laser for the treatment of leg telangiectasias. METHODS: This
      study was constructed in four phases. Phase I examined 28 patients with variable
      sized telangiectasias using 5 treatment parameters (15 J/cm2 x 1 pulse, 20 J/cm2
      x 1 pulse, 20 J/cm2 x 2 pulses, 20 J/cm2 x 3 pulses, or 30 J/cm2 x 1 pulse). Each
      patient received 3 treatments at 4 week intervals with the LPA. Patient diaries
      were obtained to examine the effects of the treatments. Subjective grading was
      performed at each follow-up visit by the investigators. Blinded objective grading
      was performed at the conclusion of the study by trained observers. Phase II
      examined the effects of these treatment parameters on varying vessel diameters.
      Vessels were grouped into small (<0.4 mm), intermediate (0.4-1.0 mm), and large
      (1.0-3.0 mm) subsets. Phase III examined the effects of a combination of LPA
      treatment followed by 23.4% hypertonic saline sclerotherapy. Subjective and
      blinded objective grading was used to determine improvement after a single
      treatment with the LPA at 20 J/cm2, single pulsed with a pulse duration of 5 or
      10 msec followed by treatment with 23.4% hypertonic saline injected 3, 7, 14, or
      28 days after laser therapy. Phase IV involved biopsies after LPA treatment alone
      at time intervals of immediately posttreatment and 5 and 21 days posttreatment.
      RESULTS: These evaluations revealed that the optimal treatment parameters for LPA
      therapy alone appeared to be 20 J/cm2, double pulsed at a repetition rate of one
      Hz. After 3 treatments at 4 week intervals, subjective grading indicated a 63%
      reduction in leg telangiectasias. Medium diameter vessels responded best with
      small vessel diameters responding poorly, if at all. The addition of 23.4%
      hypertonic saline sclerotherapy performed 3 to 7 days after laser therapy (LPA at
      20 J/cm2, single pulsed with a pulse duration of 5 msec) produced 87% reduction
      in leg telangiectasias. Biopsies after LPA treatment revealed vessel wall
      endothelial cell necrosis at 5 days with fibrosis occurring at 3 weeks. The
      optimal clinical "window" for sclerotherapy seems to coincide with the period of
      endothelial cell necrosis. CONCLUSION: LPA therapy is most effective for leg
      telangiectasias 0.4-3.0 mm in diameter. This LPA technique is significantly
      improved with the addition of sclerotherapy.

PMID- 9935097
TI  - Sleep lines.
AB  - BACKGROUND: This is a tribute to Dr. Samuel J. Stegman who in 1987 described
      "Sleep Creases." His awareness of these lines has helped us understand the
      anatomy of the underlying superficial musculoaponeurotic system (SMAS).
      OBJECTIVE: To expand upon the clinical description and the anatomical basis of
      sleep lines. METHOD: A pillow or hand test is used to accentuate sleep lines.
      Their development is linked to the underlying attachments of the SMAS. RESULTS:
      There is a correlation between the location of the underlying SMAS or aberrant
      scar tissue and sleep lines. To effectively treat these lines, the sleeping
      position must be altered or subcision of the underlying SMAS attachments and skin
      resurfacing may improve the situation. CONCLUSION: We have confirmed Dr.
      Stegman's hallmark work on sleep wrinkles. They are accentuated by pillow contact
      and the underlying SMAS.

PMID- 9935098
TI  - Linear basal cell carcinoma: report of seventeen cases and review of the
      presentation and treatment.
AB  - BACKGROUND: Linear basal cell carcinoma was first described as a distinct
      clinical morphologic variant in 1985. Subsequently, twelve cases were reported.
      OBJECTIVE: To review and identify cases of linear basal cell carcinoma in our
      institutions and determine optimal treatment based on review of our cases and
      those in the literature. METHODS: Primary basal cell carcinomas treated at the
      three campuses of Mayo Clinic and the University of Montreal were reviewed
      retrospectively, as were the twelve cases in the literature. RESULTS: Seventeen
      cases of linear basal cell carcinoma were identified. The age and sex ratios were
      similar to those of patients with standard basal cell carcinomas. Based on the
      review of the few reported cases of linear basal cell carcinoma (29), the
      percentage of aggressive histologic subtypes (38%) was increased compared with
      that in a general population. The average number of Mohs layers required for
      treatment was higher than that reported for standard basal cell carcinoma, an
      indication of increased subclinical spread. CONCLUSION: Linear basal cell
      carcinoma is an uncommonly recognized morphologic variant. Based on the small
      number of cases, these tumors have more aggressive histologic subtypes. Because
      of the possibility for increased subclinical spread, Mohs micrographic surgery
      can be considered for treatment. Further studies are needed to confirm these
      findings.

PMID- 9935099
TI  - Spindle cell lipoma of the scalp: a case report and review.
AB  - Cutaneous surgeons frequently evaluate and manage soft tissue tumors arising on
      the head and neck of adults. Of these, the most common tumor is the lipoma, and
      specific mesenchymal variants of lipoma occur classically on the head and neck.
      We describe a case of a large spindle cell lipoma of the posterior scalp, in
      order to highlight the classic location and differential diagnosis of the lipoma
      variants presenting commonly in this anatomic region. In addition, we review the
      role of preoperative imaging studies of scalp soft tissue tumors and discuss how
      imaging may assist the dermatologic surgeon in establishing the diagnosis and
      designing a rational surgical approach.

PMID- 9935100
TI  - The "pecking order" of new patients.

PMID- 9935101
TI  - ETUL increases the safety, efficiency and patient satisfaction of tumescent
      liposuction.

PMID- 9935102
TI  - Ergonomically effective grommet.

PMID- 9935104
TI  - On reaching a state of (professional) "suspended animation".

PMID- 9935103
TI  - Hypertrophic scarring from pulsed dye laser treatment.

PMID- 9935105
TI  - Extent of undermining and neurovascular trabeculae.

PMID- 9935106
TI  - Layered wound closure.

PMID- 9935107
TI  - Exercise and reproductive dysfunction.
AB  - OBJECTIVE: To provide an overview of our current understanding of exercise
      induced reproductive dysfunction and an approach to its evaluation and
      management. DESIGN: A MEDLINE search was performed to review all articles with
      title words related to menstrual dysfunction, amenorrhea, oligomenorrhea,
      exercise, and athletic activities from 1966 to 1998. The pathophysiology,
      proposed mechanisms, clinical manifestations, evaluation, and management of
      exercise-associated reproductive dysfunction were compiled. CONCLUSION(S):
      Exercise-induced menstrual irregularity appears to be multifactorial in origin
      and remains a diagnosis of exclusion. The underlying mechanisms are mainly
      speculative. Clinical manifestations range from luteal phase deficiency to
      anovulation, amenorrhea, and even delayed menarche. Evaluation should include a
      thorough history and a complete physical plus pelvic examination. Most cases are
      reversible with dietary and exercise modifications. Hormonal replacement in cases
      of a prolonged hypoestrogenic state with evidence of increased bone loss is
      recommended, although the long-term consequences of prolonged hormonal deficiency
      are ill-defined.

PMID- 9935108
TI  - Indecent proposal: $5,000 is not "reasonable compensation" for oocyte donors.

PMID- 9935109
TI  - Administration of progesterone before oocyte retrieval negatively affects the
      implantation rate.
AB  - OBJECTIVE: To compare the efficacy of two clinically accepted methods of
      progesterone supplementation during IVF. DESIGN: Prospective randomized trial.
      SETTING: A university-based IVF program. PATIENT(S): Three hundred fourteen
      stimulated IVF cycles between January 1993 and October 1994. INTERVENTION(S):
      Patients were assigned to one of two luteal phase progesterone regimens by a
      random permuted block design. In protocol A, 12.5 mg of IM progesterone was given
      12 hours before oocyte retrieval; in protocol B, 25 mg of IM progesterone was
      given on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S): Clinical
      pregnancy. RESULT(S): Patient demographic characteristics, including age,
      diagnosis, number of oocytes retrieved and fertilized, and number of embryos
      transferred, were not different between the two groups. There was no difference
      in the rate of cycle cancellation between the groups. One hundred forty ETs were
      performed in patients assigned to protocol A and 142 in patients assigned to
      protocol B. The clinical pregnancy rate in group A was 12.9% compared with 24.6%
      in group B. CONCLUSION(S): The administration of progesterone before oocyte
      retrieval is associated with a lower pregnancy rate than the administration of
      progesterone after oocyte retrieval.

PMID- 9935110
TI  - Oocyte donation: insights into implantation.
AB  - OBJECTIVE: To ascertain whether obstetric, gynecologic, or congenital variables
      affect implantation efficiency or eventual delivery in donor oocyte recipients.
      DESIGN: Clinical study. SETTING: Academic tertiary care infertility clinic.
      PATIENT(S): A total of 370 recipients. INTERVENTION(S): Fresh ET following oocyte
      donation in a hormone replacement cycle. MAIN OUTCOME MEASURE(S): Regression
      analyses were performed to detect any statistically significant difference in the
      pregnancy rate (PR), delivery rate, miscarriage rate, or implantation rate
      associated with different obstetric, gynecologic, and congenital independent
      variables while accounting for the age of the recipient in each analysis.
      RESULT(S): For all recipients, a clinical PR per transfer of 58.9% was achieved,
      with an implantation rate of 30%. A significant decline in the implantation rate
      was noted in relation to increasing age of the recipient. A history of tubal
      disease was associated with a significantly lower implantation rate and a
      significantly lower ongoing and delivered PR. Asherman's syndrome, despite
      surgical correction, appeared to negatively affect the ongoing and delivered PR.
      CONCLUSION(S): With the exceptions of recipient age and a history of tubal
      disease, all other uterine factors studied did not appear to influence the
      implantation potential of an embryo resulting from oocyte donation. A history of
      tubal disease had a distinctly negative effect on implantation efficiency and
      delivery potential for a given recipient. This finding highlights the need to
      identify the mechanisms underlying the negative effect of tubal disease so that
      donor oocyte recipients and all other patients with this cause of infertility can
      benefit from directed therapy.

PMID- 9935111
TI  - Value of ovarian stromal blood flow velocity measurement after pituitary
      suppression in the prediction of ovarian responsiveness and outcome of in vitro
      fertilization treatment.
AB  - OBJECTIVE: To evaluate whether ovarian stromal blood flow velocity after
      pituitary suppression is predictive of ovarian response and the outcome of IVF
      treatment in patients with normal basal serum FSH levels and to compare the
      predictive value of this test with age, early follicular phase serum FSH level,
      E2 level, and FSH:LH ratio. DESIGN: Prospective observational study of women
      undergoing IVF treatment. SETTING: A tertiary referral center for assisted
      reproduction. PATIENT(S): Eighty-eight women who received the long buserelin
      acetate treatment protocol. INTERVENTION(S): Transvaginal color and pulsed
      Doppler measurement of the ovarian stromal peak systolic velocity (PSV) after
      pituitary suppression and measurement of the basal serum FSH level, E2 level, and
      FSH:LH ratio. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved and
      pregnancy rate. RESULT(S): Ovarian stromal PSV was the most important single
      independent predictor of ovarian response in patients with a normal basal serum
      FSH level, when compared with age, basal FSH level, E2 level, or FSH:LH ratio.
      Patients in group 2 (PSV > or = 10 cm/s) had a significantly higher median number
      of mature oocytes retrieved (11 versus 5.5) and a higher clinical pregnancy rate
      (35.3% versus 11.3%) than patients in group 1 (PSV <10 cm/s), even after
      controlling for age. CONCLUSION(S): Ovarian stromal blood flow velocity, after
      pituitary suppression is confirmed, is predictive of ovarian responsiveness and
      the outcome of IVF treatment.

PMID- 9935112
TI  - Thyroid autoimmunity and abortion: a prospective study in women undergoing in
      vitro fertilization.
AB  - OBJECTIVE: To determine whether an association exists between the presence of
      thyroid peroxidase (TPO) antibodies before pregnancy and miscarriage in women
      without a history of habitual abortion. DESIGN: Prospective study and nested case
      control study. SETTING: Inner-city teaching hospital. PATIENT(S): Four hundred
      eighty-nine women in an IVF program. INTERVENTION(S): In the prospective study,
      we measured levels of TPO antibodies and TSH. In the nested case-control study,
      we also measured levels of anticardiolipin antibodies. MAIN OUTCOME MEASURE:
      Miscarriage. RESULT(S): One hundred seventy-three women were observed, of whom
      31% (54/173) became pregnant. Pregnancy occurred in 48% (12/25) of the antibody
      positive women and in 28% (42/148) of the antibody-negative women. Among those
      who became pregnant, miscarriage occurred in 33% (4/12) of TPO antibody-positive
      women and in 19% (8/42) of TPO antibody-negative women. The TSH level was
      abnormal (<0.2 microIU/mL) in only one of the TPO antibody-positive women who
      miscarried. The presence of anticardiolipin antibodies was not associated with
      miscarriage. CONCLUSION(S): No association was found between the presence of TPO
      antibodies before pregnancy and miscarriage in women without a history of
      habitual abortion. The presence of TPO antibodies did not adversely affect a
      woman's chances of becoming pregnant.

PMID- 9935113
TI  - Spontaneous conception after the birth of infants conceived through in vitro
      fertilization treatment.
AB  - OBJECTIVE: To investigate the incidence of spontaneous conception after the birth
      of infants conceived through IVF in couples with subfertility caused by
      endometriosis, a mild male factor, or unexplained factors, and to identify
      clinical conditions related to the occurrence of spontaneous conception. DESIGN:
      Retrospective analysis. SETTING: Department of Obstetrics and Gynecology, Akita
      University School of Medicine, Akita, Japan. PATIENT(S): One hundred forty-two
      women who conceived through IVF and 25 of the 142 women who subsequently
      conceived spontaneously. INTERVENTION(S): Patient characteristics and IVF data
      were obtained from hospital records, and follow-up data were collected through
      telephone interviews. MAIN OUTCOME MEASURE(S): Cumulative conception rate.
      RESULT(S): The cumulative conception rate at 60 months after the delivery of
      infants conceived through IVF was 18%, with most conceptions occurring within 2
      years of delivery. Proportional hazard analysis indicated that patient age was
      the most important clinical variable related to the occurrence of spontaneous
      conception. CONCLUSION(S): This study provides information that will be useful in
      counseling subfertile couples who have conceived through the use of IVF.

PMID- 9935114
TI  - Preimplantation urinary hormone profiles and the probability of conception in
      healthy women.
AB  - OBJECTIVE: To examine hormonal predictors of conception in menstrual cycles from
      normal women. DESIGN: Longitudinal study. SETTING: Community. PATIENT(S): Two
      hundred fifteen healthy female volunteers with no known fertility problems who
      were trying to conceive. INTERVENTION(S): Participants recorded menstrual
      bleeding, sexual intercourse, and collected first morning urine specimens daily
      from when they stopped contraception until they became pregnant or for 6 months
      if no clinical pregnancy was achieved. Measurements were made of urinary LH and
      urinary metabolites of estrogen and progesterone. MAIN OUTCOME MEASURE(S):
      Conception was identified by a sensitive and specific immunoradiometric assay for
      urinary hCG. RESULT(S): Statistical analyses of 189 conception and 409
      nonconception cycles controlled for sexual intercourse and interdependence of
      cycles from the same woman. Conception was more likely in cycles with lower
      baseline progesterone metabolite levels, higher ovulatory LH, and higher
      midluteal progesterone. Midluteal estrogen also was elevated in conception cycles
      when examined without adjusting for other hormone levels, but this finding did
      not persist after multivariate adjustment. CONCLUSIONS: Menstrual cycles in
      normal women vary in their hormonal quality in ways that are predictive of cycle
      fertility.

PMID- 9935115
TI  - A novel in vitro experimental model for ovarian endometriosis: the three
      dimensional culture of human ovarian surface epithelial cells in collagen gels.
AB  - OBJECTIVE: To develop an in vitro experimental model of ovarian endometriosis
      using human cells and to investigate the pathogenesis of endometriosis. DESIGN:
      Controlled in vitro coculture study. SETTING: A department of obstetrics and
      gynecology at a university hospital. PATIENT(S): Ovaries and endometrium were
      obtained from patients who underwent a hysterectomy because of gynecologic
      disease. INTERVENTION(S): Human ovarian surface epithelial (OSE) cells were
      cultured alone and OSE cells and endometrial stromal (ES) cells were cultured
      together in a three-dimensional collagen gel culture system with or without the
      addition of E2. MAIN OUTCOME MEASURE(S): The aggregated collagen gels containing
      the cultured cells were examined morphologically. RESULT(S): The OSE cells in
      single culture with E2 formed circular arrangements. These cells were
      immunohistochemically positive for cytokeratin but negative for epithelial
      membrane antigen. In the cocultures of OSE and ES cells with E2, the OSE cells
      formed a lumen structure surrounded by ES cells. Immunoreactivity for cytokeratin
      and epithelial membrane antigen was detected in the glandular cells and cilia
      were identified on the cell surface by electron microscopy. Without the addition
      of E2, no structures were detected. CONCLUSION(S): A new in vitro experimental
      model was established with the aid of human OSE cells. Endometriotic lesions can
      arise through a process of metaplasia from OSE cells in the presence of E2 and ES
      cells.

PMID- 9935116
TI  - Whole explants of peritoneum and endometrium: a novel model of the early
      endometriosis lesion.
AB  - OBJECTIVE: To determine whether whole fragments of endometrium can adhere to
      peritoneum with intact mesothelium. DESIGN: Tissue culture and
      immunohistochemical study. SETTING: University medical center. PATIENT(S):
      Reproductive-age women undergoing surgery for benign conditions. INTERVENTION(S):
      Explants of human peritoneum from the anterior abdominal wall and the posterior
      surface of the uterus were cultured with whole fragments of mechanically
      dispersed endometrium. MAIN OUTCOME MEASURE(S): Adhesion of endometrial fragments
      to the surface of the peritoneum was evaluated. Adherent endometrium was
      identified with the use of the dissecting microscope and by the performance of
      serial sections of the peritoneum explants. Immunohistochemical staining of the
      mesothelium with antibodies to cytokeratin was used to ensure an intact layer of
      mesothelium beneath the endometrial implants. Transmission electron microscopy
      also was used to evaluate this adhesion process. RESULT(S): Endometrium was
      identified attached to the surface of the peritoneum. Most of the implants did
      not have identifiable mesothelium beneath them, but most had intact mesothelium
      running up to the point of attachment. Approximately 10% of the endometrial
      implants had intact mesothelium at the site of attachment. Endometrial stromal
      cells, and not epithelium, attached to the mesothelium. CONCLUSION(S):
      Endometrium can attach to the mesothelial surface of the peritoneum. Endometrial
      stromal cells are involved in this attachment. Invasion through the mesothelium
      seems to occur rapidly.

PMID- 9935117
TI  - Production of steroids from human cumulus cells treated with different
      concentrations of gonadotropins during culture in vitro.
AB  - OBJECTIVE: To evaluate the output of E2 and progesterone produced by cumulus
      cells, derived from mature and immature oocytes, in culture medium. DESIGN:
      Prospective randomized study. SETTING: McGill Reproductive Center, Royal Victoria
      Hospital, McGill University, Montreal, Quebec, Canada. PATIENT(S): Twenty-one
      women, <38 years of age and with normal menstrual cycles, who were undergoing
      intracytoplasmic sperm injection for assisted reproduction. INTERVENTION(S):
      Culture medium with or without fetal bovine serum (FBS) supplemented with either
      a physiologic (75 mIU/mL) or a supraphysiologic (7,500 mIU/mL) concentration of
      gonadotropins. MAIN OUTCOME MEASURE(S): Comparison of steroid levels in culture
      medium. RESULT(S): Estradiol secretion was significantly increased in the culture
      medium with FBS supplemented with both concentrations of FSH alone compared with
      control. However, E2 secretion was inhibited by both concentrations of FSH with
      LH. The level of E2 was undetectable in the medium without FBS even after
      supplementation with both concentrations of FSH alone, hCG alone, and FSH with
      LH. Progesterone production was increased in the medium with FBS supplemented
      with FSH alone, hCG alone, and FSH with LH compared with control. There was no
      difference in progesterone levels in the culture medium without FBS supplemented
      with both concentrations of FSH alone and hCG alone compared with control.
      However, progesterone secretion was increased in the medium without FBS
      supplemented with a physiologic concentration of FSH with LH. CONCLUSION(S):
      Culture medium with FBS supplemented with a physiologic and a supraphysiologic
      concentration of FSH stimulates E2 secretion from cumulus cells derived from
      mature and immature oocytes. This suggests that it may be not necessary to add E2
      to the culture medium for maturation in vitro of immature human oocytes retrieved
      from patients undergoing stimulated cycles.

PMID- 9935118
TI  - Immunomodulation with interleukin-10 and interleukin-4 compared with ketorolac
      tromethamine for prevention of postoperative adhesions in a murine model.
AB  - OBJECTIVE: To assess the effects of two macrophage down-regulating cytokines
      (interleukin [IL]-10 and IL-4) and the nonsteroidal anti-inflammatory drug
      ketorolac tromethamine on postoperative adhesion formation. DESIGN: Randomized
      controlled trial. SETTING: Research center vivarium. ANIMAL(S): Six-week-old
      Swiss Webster mice. INTERVENTION(S): One hundred eighty animals were randomized
      to serve as nonsurgical controls or to undergo a standardized adhesion-inducing
      procedure. Subsequently, animals were randomized to nine different treatment
      groups to receive no injections, phosphate-buffered saline (PBS) only, IL-10, IL
      4, ketorolac, IL-10 plus IL-4, IL-10 plus ketorolac, IL-4 plus ketorolac, or all
      three agents. MAIN OUTCOME MEASURE: Adhesion scores on postoperative day 10.
      RESULT(S): Postoperative adhesion scores were significantly reduced in all groups
      of animals treated with IL-10 or ketorolac. Animals treated with IL-4 showed a
      nonsignificant trend toward reduction of adhesions. There were significantly more
      animals with adhesion scores of < or = 3 in the IL-10 and ketorolac treatment
      groups than in the control groups receiving no treatment or PBS only.
      CONCLUSION(S): Although treatment with IL-10 and ketorolac did not completely
      prevent adhesion formation, treatment with these drugs did lead to a significant
      reduction in adhesion formation. Adhesions also tended to be thin and filmy
      rather than thick and vascular. Addition of IL-4 did not augment these effects.

PMID- 9935119
TI  - A subset of CD56+ large granular lymphocytes in first-trimester human decidua are
      proliferating cells.
AB  - OBJECTIVE: To determine whether the unusually high number of CD56+ large granular
      lymphocytes (LGL) in the decidua of early human pregnancy arises from selective
      migration or in situ proliferation. DESIGN: Controlled clinical study. SETTING:
      Academic research environment. PATIENT(S): Thirty healthy women undergoing
      therapeutic abortion of an intact pregnancy at 5-11 weeks' gestation.
      INTERVENTION(S): Decidua was obtained by suction curettage; tissue and isolated
      cells were subjected to immunohistochemical and flow cytometric investigation.
      MAIN OUTCOME MEASURE(S): Proliferation rate of LGL. RESULT(S): The proportion of
      CD56+ cells positive for the proliferation-associated Ki-67 antigen was found to
      be 7%-23.5% by three different methods of investigation. These findings are
      consistent with those of flow cytometric analysis of the nuclear phase, which
      revealed 6%-22% of the LGL nuclei to be in the phases S+G2+M. CONCLUSION(S): The
      various methods of investigation revealed marked proliferative activity in the
      LGL of early pregnancy decidua. This finding suggests that in situ proliferation
      may be responsible for the high density of these cells in the decidua.

PMID- 9935120
TI  - Assessment of interlaboratory and intralaboratory sperm morphology readings with
      the use of a Hamilton Thorne Research integrated visual optical system semen
      analyzer.
AB  - OBJECTIVE: To evaluate the level of variance produced in a multicenter study with
      the use of a computer-assisted sperm morphology analyzer. DESIGN: A multicenter,
      prospective, blinded study. SETTING: Assisted reproduction research laboratories.
      PATIENT(S): Semen samples produced for assisted reproductive procedures.
      INTERVENTION(S): Hamilton Thorne Research (Beverly, MA) integrated visual optical
      system semen analyzers were used at five different centers to evaluate the same
      set of 30 slides that were prepared and numerically coded at Tygerberg Hospital
      in Tygerberg, South Africa. MAIN OUTCOME MEASURE(S): The percentage of normal
      sperm. RESULT(S): Interlaboratory coefficients of variation (CVs) ranged between
      16.31% and 23.09%. One of the participating laboratories produced an
      approximately 14% (-6.5-7.7) limits of agreement analysis, with a CV of 11.36%,
      for its duplicate readings. The use of a 10% normal sperm morphology cutoff point
      to determine discordance levels produced rates ranging between 10% and 23.3% for
      the interlaboratory and intralaboratory readings. This level of discordance
      equates with < or = 7 of the corresponding readings from two laboratories falling
      into a different normal sperm morphology group (< or = 10% or >10%).
      CONCLUSION(S): The magnitudes of variation produced by the readings performed in
      our study reached the same level as for the manual evaluation of sperm
      morphology. A < 10% CV can be obtained if the correct quality control measures
      are implemented.

PMID- 9935121
TI  - Decreased expression of the c-kit receptor is associated with increased apoptosis
      in subfertile human testes.
AB  - OBJECTIVE: To examine the expression of the c-kit receptor and its ligand, stem
      cell factor, and their possible relation with apoptosis in infertile men. DESIGN:
      Prospective laboratory study. SETTING: Urology laboratory in a university
      hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of
      subfertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of the c
      kit receptor protein, stem cell factor, and apoptosis in the testes. RESULT(S):
      The c-kit receptor was strongly present in Leydig cells and type A spermatogonia
      of normal testes, with decreased staining in Leydig cells and type A
      spermatogonia of testes with maturational arrest, and staining in only Leydig
      cells of Sertoli cell-only specimens. Stem cell factor was demonstrated in Leydig
      cells and Sertoli cells in all specimens. Western blotting demonstrated the 150
      kd c-kit protein in the normal testes and the testes with maturational arrest,
      but not in the testes with the Sertoli cell-only pattern. Stem cell factor was
      expressed in all specimens, with a protein size of 45 kd. Increased apoptosis was
      demonstrated in type A spermatogonia and spermatocytes of tissue with
      maturational arrest compared with normal testicular tissue. CONCLUSION(S): C-kit
      receptor expression is decreased in subfertile testicular tissue compared with
      normal testicular tissue. Stem cell factor expression is present in Leydig cells
      and Sertoli cells. Increased apoptosis is seen in tissue with maturational arrest
      compared with normal tissue.

PMID- 9935122
TI  - Corticosteroids do not influence ovarian responsiveness to gonadotropins in
      patients with premature ovarian failure: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine the effect of corticosteroids on ovarian responsiveness
      to exogenous gonadotropins in patients with idiopathic premature ovarian failure
      (POF). DESIGN: Placebo-controlled, randomized, double-blind, multicenter study.
      SETTING: Two tertiary care academic centers for reproductive endocrinology and
      fertility and two general teaching hospitals. PATIENT(S): One hundred patients
      with idiopathic POF intended to enter the study. The study was discontinued after
      36 patients failed to ovulate. INTERVENTION(S): Endocrine and immune parameters
      were tested on days 1 and 15. On day 1, subjects were randomized to receive
      either 9 mg of dexamethasone daily or placebo. From day 5 onward, 300 IU of hMG
      daily was added for 10 days in both groups. The dosage of dexamethasone was
      decreased stepwise in the second week and discontinued after day 15. Patients
      were monitored by transvaginal ultrasonography and by determining serum E2
      levels. MAIN OUTCOME MEASURE(S): Ovulation rate. Fifty patients would have to be
      included in each study group to detect a statistically significant difference of
      20% in the ovulation rate between the two groups with alpha = 0.05 and beta = 0.1
      (one-tailed test). RESULT(S): No ovulation was recorded in the first 36 patients.
      Interim analysis showed that the 95% confidence intervals of an ovulation rate of
      0 were 0-17% for the dexamethasone arm (n = 19) and 0-19% for the placebo arm (n
      = 17). Because the preset objective (a difference of 20%) would never be reached,
      the study was discontinued. CONCLUSION(S): Corticosteroids do not influence
      ovarian responsiveness to gonadotropins in patients with idiopathic POF.

PMID- 9935123
TI  - Increased prevalence of luteinizing hormone beta-subunit variant in patients with
      premature ovarian failure.
AB  - OBJECTIVE: To evaluate the significance of an LH variant with a mutant beta
      subunit (Trp8 to Arg8 and Ile15 to Thr15) in gynecologic disease, including
      infertility. DESIGN: Clinical study. SETTING: Department of Obstetrics and
      Gynecology, Shimane Medical University Hospital, Izumo, Japan. PATIENT(S): Two
      hundred forty-five Japanese women with endocrine disorders and/or gynecologic
      disease and 153 healthy, nonpregnant, fertile Japanese women. INTERVENTION(S): A
      blood sample was collected. MAIN OUTCOME MEASURE(S): The ratio of LH values from
      the SPAC-S and Immulyze assays (LH ratio: SPAC-S LH/Immulyze LH) was used to
      determine variant (< or =0.5) or wild-type (>0.5) LH status according to a
      demonstrated relation between the ratio and the sequence of the LH beta-subunit
      gene. RESULT(S): The LH ratio was lower (0.80+/-0.31) in the 245 patients than in
      the controls (1.00+/-0.38), and the variant was more frequent in the patients
      (18.4%) than in the controls (8.5%). We found no difference in the frequency of
      the variant between infertile and fertile patients. The prevalence of infertility
      did not differ between patients with variant LH and patients with normal LH.
      Ovulatory disorders, hyperprolactinemia, premature ovarian failure, menstrual
      disorders, and luteal insufficiency were significantly more frequent in patients
      with the variant. CONCLUSION(S): Variant LH may contribute to female reproductive
      disorders, including infertility and premature ovarian failure.

PMID- 9935124
TI  - Plasma immunoglobulins in patients with severe ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To assess immunoglobulin (Ig) concentrations in plasma and ascitic
      fluid of patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN:
      Controlled clinical study. SETTING: Tertiary medical center. PATIENT(S): Ten
      patients with severe OHSS after ovulation induction for IVF and 10 controls who
      had undergone similar ovulation induction and did not develop OHSS.
      INTERVENTION(S): Three blood samples were obtained from each OHSS patient: one at
      the time of hospitalization for severe OHSS, one when significant clinical
      improvement was evident, and one at the first follow-up visit after discharge
      from the hospital. Blood samples were drawn from control patients 6-8 days after
      ET. Ascitic fluid was obtained from all patients with OHSS by therapeutic
      paracentesis. MAIN OUTCOME MEASURE(S): Immunoglobulin concentrations were assayed
      by radial immunodiffusion. RESULT(S): Significantly lower levels of gamma
      globulins, specifically IgG and IgA, were detected in the plasma of patients with
      severe OHSS, whereas alpha- and beta-globulin levels as well as IgM levels were
      not significantly different from those in controls. Both IgG and IgA levels
      increased as patients clinically improved. Ascitic fluid contained high IgG,
      moderate IgA, and negligible IgM levels. CONCLUSION: Severe OHSS is characterized
      by hypogammaglobulinemia, attributed to leakage of medium-molecular-weight
      immunoglobulins such as IgG and IgA to the peritoneal cavity.

PMID- 9935125
TI  - Induction of ovulation with the use of a starting dose of 50 units of recombinant
      human follicle-stimulating hormone (Puregon).
AB  - OBJECTIVE: To determine whether a starting dose of 50 units of recombinant FSH
      (follitropin beta, Puregon; Organon Laboratories Limited, Cambridge, United
      Kingdom) produces a follicular response in patients with clomiphene citrate
      resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective observational
      study. SETTING: Routine clinical practice in a teaching hospital fertility unit.
      PATIENT(S): Patients with clomiphene citrate-resistant PCOS who wanted to become
      pregnant. INTERVENTION(S): Low-dose step-up protocol of SC recombinant FSH
      administration, monitored prospectively by transvaginal ultrasonography and
      retrospectively by serum endocrine assays taken at each monitoring visit. MAIN
      OUTCOME MEASURE(S): Rate and size of follicular growth, recombinant FSH
      requirement, E2 response, ovulation, cycle cancellation, and pregnancy.
      RESULT(S): All patients exhibited a follicular response: Six patients ovulated,
      of whom two conceived and four had their cycles cancelled because of
      overstimulation. One patient did not ovulate despite the development of a
      follicle. CONCLUSION(S): Recombinant FSH can be used successfully to stimulate
      follicular growth at a starting dose of 50 IU.

PMID- 9935126
TI  - Effect of exogenous gonadotropins on endometrial maturation in oocyte donors.
AB  - OBJECTIVE: To determine the effects of controlled ovarian hyperstimulation (COH)
      on endometrial maturation. DESIGN: Prospective, before and after evaluation of
      midluteal endometrial biopsies in oocyte donor's spontaneous and subsequent COH
      cycles. SETTING: Tertiary academic medical center assisted reproductive
      technologies clinic. PATIENT(S): Nineteen oocyte donors. INTERVENTION(S):
      Exogenous gonadotropins, endometrial biopsies. MAIN OUTCOME MEASURE(S):
      Endometrial histology and an immunohistochemical marker of uterine receptivity,
      the alphavbeta3 vitronectin. RESULT(S): Glandular and stromal dyssynchrony was
      more common after COH in 16 (80%) of 20 cycles than 6 (30%) of 20 spontaneous
      cycles (P <.05). Glandular lag was more frequent in COH cycles and unaffected by
      progesterone administration. The beta3 subunit of the alphavbeta3 vitronectin
      receptor was present in 9 (45%) of 20 spontaneous and 2 (10%) of 20 COH cycles (P
      <.05). CONCLUSION(S): Exogenous gonadotropin use in healthy reproductive age
      women did not result in endometrial evidence of a luteal phase defect. A greater
      incidence of glandular-stromal dyssynchrony resulted from the use of exogenous
      gonadotropins. The presence of alphavbeta3 was noted in most endometrial
      specimens demonstrating in phase glandular maturation. We conclude that
      endometrial dyssynchrony that results from delayed glandular development most
      likely represents a normal histologic variant.

PMID- 9935127
TI  - Effect of opioid blockade on insulin and growth hormone (GH) secretion in
      patients with polycystic ovary syndrome: the heterogeneity of impaired GH
      secretion is related to both obesity and hyperinsulinism.
AB  - OBJECTIVE: To investigate the involvement of opioid tone, obesity, and
      hyperinsulinemia in GH secretion in women with polycystic ovary syndrome (PCOS).
      DESIGN: Controlled clinical study. SETTING: Catholic University of Sacred Heart
      School of Medicine in Rome, Italy. PATIENT(S): Twenty-two patients with PCOS and
      14 healthy, normally ovulating volunteers, matched for age and body mass index.
      INTERVENTION(S): Patients underwent a GH-releasing hormone (GHRH) test and an
      oral glucose tolerance test before and after 4-5 weeks of treatment with 50 mg/d
      of naltrexone. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin,
      glucose, steroids, and gonadotropins, as well as the GH area under the curve (AUC
      GH) and the insulin area under the curve (AUC-I), were measured before and after
      naltrexone treatment. RESULT(S): In patients with PCOS, the administration of
      naltrexone increased the GH response to the GHRH test without interfering with
      the insulin response to the oral glucose tolerance test. However, the GH response
      to the GHRH test was improved significantly only in lean patients with PCOS,
      whereas obese patients with PCOS did not show any improvement in GH secretion. In
      obese control subjects, the treatment reduced plasma basal insulin concentrations
      and increased the AUC-GH, whereas in lean control subjects, the treatment reduced
      the GHRH-induced response. In normoinsulinemic patients with PCOS, the GH
      response to the GHRH test increased significantly after treatment, whereas the
      AUC-I was not affected. In hyperinsulinemic patients with PCOS, treatment with
      naltrexone significantly reduced the AUC-I, whereas the AUC-GH increased only in
      lean hyperinsulinemic patients with PCOS. CONCLUSION(S): Naltrexone treatment
      improves GHRH-induced GH secretion in patients with PCOS. However, this GH
      response is heterogeneously represented in relation to both obesity and
      hyperinsulinism.

PMID- 9935128
TI  - Prospective randomized study comparing the long-acting gonadotropin-releasing
      hormone agonist triptorelin, flutamide, and cyproterone acetate, used in
      combination with an oral contraceptive, in the treatment of hirsutism.
AB  - OBJECTIVE: To compare triptorelin, cyproterone acetate (CPA), and flutamide, in
      combination with an oral contraceptive, in the treatment of hirsutism. DESIGN:
      Prospective randomized study. SETTING(S): Tertiary care hospital. PATIENT(S):
      Thirty-nine hirsute women with idiopathic or functional ovarian hyperandrogenism.
      INTERVENTION(S): Patients were randomly assigned to receive triptorelin (3.75 mg
      IM every 28 days), CPA (100 mg/d orally on days 1-10 of the menstrual cycle), or
      flutamide (250 mg orally twice daily). All the patients also received a triphasic
      oral contraceptive. MAIN OUTCOME MEASURE(S): Before and after 3 and 9 months of
      treatment, the Ferriman-Gallwey score, hepatic function, and gonadal and adrenal
      steroid profiles were evaluated. RESULTS: Thirty-three patients completed the 9
      month study period. The Ferriman-Gallwey score decreased in all the groups. In
      the patients treated with CPA or flutamide, a decrease in the hirsutism score was
      noted as soon as after 3 months of treatment. This decrease was more pronounced
      after 9 months of treatment, especially in the patients who received flutamide,
      who had lower hirsutism scores compared with the other treatment groups. None of
      the patients had abnormal liver function test results. There was a mild increase
      in serum lipid concentrations, mostly in the group treated with triptorelin.
      CONCLUSION(S): Triptorelin, CPA, and flutamide are effective drugs for the
      treatment of hirsutism. Flutamide results in a greater reduction in the hirsutism
      score, but CPA also offers satisfactory results at a much lower cost. Triptorelin
      has no advantages over flutamide and CPA, and is the most expensive of the three
      drugs tested.

PMID- 9935129
TI  - Two-year prospective, randomized trial comparing an innovative twice-a-week
      progestin regimen with a continuous combined regimen as postmenopausal hormone
      therapy.
AB  - OBJECTIVE: To compare compliance, symptom control, bleeding patterns, endometrial
      response, and lipid changes in postmenopausal women treated with transdermal E2
      and a regimen of either intermittent or continuous dosing of progestin. DESIGN:
      Randomized, prospective study. SETTING: Menopausal Outpatient Clinic at an
      academic tertiary care hospital. PATIENT(S): One hundred women who had reached
      menopause naturally and had been amenorrheic for at least 1 year. Fifty women
      were randomly assigned to receive each regimen. INTERVENTION(S): All patients
      received 50-microg E2 patches and medroxyprogesterone acetate, either 5 mg twice
      per week or 2.5 mg daily. The bleeding pattern was registered in diary cards.
      Endometrial status was assessed by vaginal ultrasound and endometrial biopsy.
      Lipid levels were measured by ELISA. MAIN OUTCOME MEASURE(S): The number of
      patients who dropped out of the study and the number of days each patient
      reported spotting or bleeding were recorded. Endometrial thickness was measured
      and histologic examination of the endometrial tissue was performed. Plasma levels
      of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and
      low-density lipoprotein cholesterol were measured. RESULT(S): Fourteen women
      dropped out of the intermittent dosing group and 13 dropped out of the continuous
      dosing group. Irregular spotting or bleeding occurred at a similar rate in both
      groups. Biopsies performed at the end of the study showed adequate endometrial
      stabilization in both groups. No significant changes in lipid levels were
      detected with either regimen. CONCLUSION(S): Both regimens were similarly
      effective. The high rate of atrophic endometria suggests the possibility of
      further reduction of the progestin dose.

PMID- 9935130
TI  - Effect of short-term hormone replacement therapy on left ventricular mass and
      contractile function.
AB  - OBJECTIVE: To determine the effect of hormone replacement therapy (HRT) on
      cardiac structure and function and whether these changes are related to changes
      in blood volume. DESIGN: Open-label pilot study. SETTING: Academic medical
      center. PATIENT(S): Eighteen healthy postmenopausal women. INTERVENTION(S): We
      administered medroxyprogesterone acetate orally, 5 mg/d for 2 months followed by
      2 months of oral sequential 17beta-estradiol, 1 mg/d plus medroxyprogesterone
      acetate, 10 mg/d for the last 12 days of each month. MAIN OUTCOME MEASURE(S):
      Cardiac output, stroke volume, heart rate, end diastolic volume, end systolic
      volume, ejection fraction, and left ventricular mass were measured by
      echocardiography; blood and plasma volumes were measured using 125I-albumin
      dilution. RESULT(S): Cardiac output, stroke volume, left ventricular mass, end
      diastolic volume, and ejection fraction increased by 12.8%, 11.7%, 9.4%, 7.2%,
      and 10.9%, respectively, by 16 weeks. End systolic volume decreased, whereas
      heart rate was unaffected. There was a significant increase in blood volume
      (5.2%) and plasma volume (4.8%) from baseline during treatment, which could
      explain the increased cardiac output but not the increased ejection fraction.
      CONCLUSION(S): Hormone replacement therapy causes modest but significant
      increases in cardiac output, ejection fraction, and left ventricular mass. These
      pilot data suggest a direct myocardial effect of HRT that is preload independent.

PMID- 9935131
TI  - Monozygotic twinning associated with mechanical assisted hatching.
AB  - OBJECTIVE: To determine the effect of mechanical assisted hatching on the
      pregnancy rate (PR). DESIGN: A retrospective comparative analysis of hatched
      versus nonhatched consecutive assisted reproductive technology (ART) cycles.
      SETTING: A hospital-based ART program. PATIENT(S): Patients undergoing ART
      treatment with assisted hatching (1994-1996) were compared with patients who did
      not have assisted hatching (1990-1993). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Pregnancy rate, multiple PR, and rate of monozygotic twinning.
      RESULT(S): With hatching, the clinical PR per ET increased from 25.2% to 37.1%
      and the multiple PR per ET increased from 6.8% to 13.1%. In the nonhatched
      series, there were no monozygotic twins compared with eight cases in the hatched
      series (1.2% per ET). CONCLUSION(S): Mechanical assisted hatching increases the
      PR but concomitantly elevates the rate of multiple gestation and multiple
      gestation of high order. There is a particularly high risk of monozygotic
      twinning with mechanical hatching.

PMID- 9935132
TI  - The detrimental effect of increased endometrial thickness on implantation and
      pregnancy rates and outcome in an in vitro fertilization program.
AB  - OBJECTIVE: To determine whether there is a maximal value for endometrial
      thickness, as measured on the day of hCG administration, above which implantation
      and pregnancy are unlikely to occur. DESIGN: Retrospective analysis. SETTING: A
      university-based tertiary care center for assisted reproductive technology.
      PATIENT(S): A total of 809 IVF cycles in 623 patients resulting in ET.
      INTERVENTION(S): Endometrial thickness was measured by means of transvaginal
      ultrasound on the day of hCG administration. Cycles were divided into two groups
      based on endometrial thickness. Group A consisted of 680 cycles with "normal"
      endometrial thickness (7-14 mm), and group B included 37 cycles with "increased
      endometrial thickness" (>14 mm). MAIN OUTCOME MEASURE(S): Implantation, clinical
      pregnancy and miscarriage rates. RESULT(S): Group B cycles had significantly
      lower implantation and pregnancy rates compared with group A (3% versus 15% and
      8.1% versus 29.7%, respectively). Two of 3 pregnancies (66.6%) from group B
      miscarried, compared with 44 of 202 (21.8%) pregnancies in group A.
      CONCLUSION(S): Patients with endometrial thickness of > 14 mm on the day of hCG
      administration comprise approximately 5% of the patients who undergo ET in our
      program. Our experience suggests that implantation and pregnancy rates are
      significantly reduced, and miscarriage rates may be increased in this group.

PMID- 9935133
TI  - Control of air quality in an assisted reproductive technology laboratory.
AB  - OBJECTIVE: To investigate the effect of improved air quality on IVF and
      subsequent embryo development. DESIGN: Retrospective cohort study. SETTING:
      Hospital-based IVF facility composed of an anteroom, a cleanroom, and an adjacent
      operating room. PATIENT(S): Two-hundred seventy-five couples requesting IVF
      between 1993 and 1997. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Particle
      counts (sizes 0.3, 0.5, 1.0, and 5.0 microm); IVF rates; and embryo quality
      (stage and grade). RESULT(S): Clinical pregnancy rates decreased from 35% in 1993
      to 16% in 1994 (numerous construction odors were detected during 1994) and
      increased steadily after the cleanroom was built (rates for 1995-1997 were 20%,
      32%, and 59%, respectively). Fertilization rates decreased between 1993 (74%) and
      1994 (60%) and then steadily increased after cleanroom installation (62% in 1995,
      71% in 1996, and 69% in 1997). The proportion of embryos past the four-cell stage
      decreased from 66% in 1993 to 61% in 1994 but then increased steadily in the
      years after the cleanroom was built (78%, 77%, and 83% in 1995, 1996, and 1997,
      respectively). During the same 5-year period, there were no differences in embryo
      quality or number of embryos transferred. CONCLUSION(S): Construction of a Class
      100 cleanroom improved air quality and IVF rate and increased the number of
      embryos past the four-cell stage available for transfer.

PMID- 9935134
TI  - Should patients who are suspected of having an ectopic pregnancy undergo physical
      examination?
AB  - OBJECTIVE: To determine whether physical examination is useful for patients with
      suspected ectopic pregnancy (EP) for whom transvaginal sonography is performed
      and serum hCG levels are measured. DESIGN: Prospective study. SETTING: Two large
      teaching hospitals. PATIENT(S): Three hundred eighty-two patients with suspected
      EP, based on a positive urine pregnancy test and the presence of abdominal pain,
      vaginal bleeding, or risk indicators. INTERVENTION(S): Abdominal examination,
      speculum inspection, and digital vaginal examination. MAIN OUTCOME MEASURE: A
      final diagnosis made by transvaginal sonography, serum hCG measurement, and, if
      necessary, confirmatory laparoscopy. RESULT(S): One hundred sixteen (30%) of the
      382 patients had an EP. At external abdominal examination, rebound tenderness and
      muscular rigidity had likelihood ratios of 3.7 and 8.0, respectively. Findings at
      speculum inspection and digital vaginal examination had likelihood ratios between
      0.33 and 2.4. Logistic regression analysis showed that the additional information
      provided by physical examination for the diagnosis of EP is limited compared with
      the information provided by transvaginal sonography and serum hCG measurement
      alone. CONCLUSION: On the basis of our results, we believe that vaginal digital
      examination for patients with suspected EP is unnecessary.

PMID- 9935135
TI  - A combined surgical and radiologic technique for creating a functional neo
      endocervical canal in a case of partial congenital cervical atresia.
AB  - OBJECTIVE: To recanalize the endocervical canal in a patient with partial
      congenital cervical atresia. DESIGN: Case report. SETTING: University hospital.
      PATIENT: A 16-year-old girl referred with a history of primary amenorrhea,
      polycystic ovaries, and intermittent abdominal pain. Physical examination
      revealed a normal vagina and external cervical os, but magnetic resonance imaging
      revealed a solid endocervical tract. INTERVENTION(S): At laparotomy the
      endometrial cavity was accessed transfundally and outlined by injection of water
      soluble contrast. A trocar needle was guided transvaginally into the uterus, the
      tract was dilated, and a 12F stent was placed. Oral contraceptives (OCs) and
      antibiotics were continued postoperatively. MAIN OUTCOME MEASURE(S):
      Hysterosalpingography and clinical follow-up. RESULT(S): The operation and
      postoperative course were uneventful. Withdrawal bleeding occurred at 8 weeks,
      after discontinuation of the OCs, at which time the stent was expelled. Later
      follow-up revealed recurrent narrowing, and the stent was replaced for 14 more
      weeks. After stent removal, regular menses continued (7 months to date).
      CONCLUSION: In select cases of congenital cervical atresia, recanalization may be
      safely performed with the use of the combined surgical-radiologic technique
      described, with good short-term outcome.

PMID- 9935136
TI  - Preimplantation genetic diagnosis of Marfan syndrome with the use of fluorescent
      polymerase chain reaction and the Automated Laser Fluorescence DNA Sequencer.
AB  - OBJECTIVE: To develop and apply clinical preimplantation genetic diagnosis (PGD)
      for Marfan syndrome. DESIGN: Case report. SETTING: Centers for medical genetics
      and reproductive medicine in university hospitals. PATIENT(S): One couple in
      which the husband was affected with Marfan syndrome. INTERVENTION(S): The couple
      underwent three intracytoplasmic sperm injection cycles. MAIN OUTCOME MEASURE(S):
      The correct diagnosis was obtained for embryos in three PGD cycles. RESULT(S):
      Although all the PGD cycles were followed by ET, no pregnancy ensued.
      CONCLUSION(S): This assay can provide a reliable and accurate preimplantation
      diagnosis of Marfan syndrome.

PMID- 9935137
TI  - Can noninvasive diagnostic tools predict tubal rupture or active bleeding in
      patients with tubal pregnancy?
AB  - OBJECTIVE: To evaluate the ability of noninvasive diagnostic tools to predict
      tubal rupture and active bleeding in patients with tubal pregnancy. DESIGN:
      Prospective cohort study. SETTING: Two large teaching hospitals in Amsterdam, The
      Netherlands. PATIENT(S): Consecutively seen patients with suspected tubal
      pregnancy who were scheduled to undergo confirmative laparoscopy. MAIN OUTCOME
      MEASURE(S): Tubal rupture and/or active bleeding confirmed at laparoscopy.
      RESULT(S): Sixty-five (23%) of 288 patients had tubal rupture and/or active
      bleeding at laparoscopy. Abdominal pain, rebound tenderness on abdominal
      examination, fluid in the pouch of Douglas at transvaginal ultrasound
      examination, and a low serum hemoglobin level were independent predictors of
      tubal rupture and/or active bleeding. Pregnancy achieved with the use of IVF-ET
      and the presence of an ectopic gestational sac or an ectopic mass at ultrasound
      examination reduced the risk of tubal rupture. Abdominal pain was the most
      sensitive predictor, with a sensitivity of 95%. CONCLUSION(S): Because the
      nonsurgical management of tubal pregnancy should be used only when the risk of
      tubal rupture and/or active bleeding is low, it can be safely applied in only a
      limited number of patients.

PMID- 9935138
TI  - Computerized assessment of endometrial echogenicity: clues to the endometrial
      effects of premature progesterone elevation.
AB  - OBJECTIVE: To determine whether premature progesterone elevation affects the
      timing of hyperechogenic transformation of the endometrium during the early
      luteal phase of controlled ovarian hyperstimulation (COH) cycles. DESIGN:
      Prospective analysis. SETTING: Assisted Reproduction Unit, Hopital Antoine
      Beclere, Clamart, France. PATIENT(S): Fifty-nine women undergoing 59 IVF-ET
      cycles. INTERVENTION(S): Patients underwent COH with a GnRH agonist and hMG.
      Endometrial echogenicity was assessed on the days of hCG administration, oocyte
      retrieval, and ET. Results are expressed as the extent of submyometrial
      hyperechogenic area in relation to the total endometrial surface as determined by
      a computer-assisted analysis system. Patients were sorted according to whether
      their plasma progesterone level exceeded 0.9 ng/mL (n = 26) or not (n = 33) on
      the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial echogenicity.
      RESULT(S): On the day of hCG administration, the degree of endometrial
      echogenicity was similar in both groups (41% vs. 40%), but after hCG
      administration, it increased significantly faster in the high progesterone group
      than in the low progesterone group (70% vs. 63% at oocyte retrieval and 90% vs.
      79% at ET, respectively). CONCLUSION(S): End-follicular phase elevation in plasma
      progesterone (>0.9 ng/mL on the day of hCG administration) was associated with a
      faster increase in endometrial echogenicity during the early luteal phase of COH
      cycles. This observation is consistent with the hypothesis that premature
      progesterone elevation hastens the secretory transformation of the endometrium.

PMID- 9935139
TI  - Enteric nervous system and endometriosis--connection?

PMID- 9935140
TI  - Predictive value of serum estradiol levels for IVF pregnancy outcome after
      gonadotropin stimulation?

PMID- 9935141
TI  - Increases in unsafe sex and rectal gonorrhea among men who have sex with men--San
      Francisco, California, 1994-1997.
AB  - Reductions in AIDS cases among men who have sex with men (MSM) have been
      attributed in part to widespread declines in unprotected anal sex since the mid
      1980s and use of increasingly effective antiretroviral therapy (ART) since the
      mid-1990s. Because data about HIV infection incidence are limited, other
      indicators of transmission risk have been used. In San Francisco, data from
      annual behavioral surveys among MSM (1994-1997) and from the sexually transmitted
      disease (STD) surveillance program (1990-1997) were analyzed to characterize
      changes in HIV risk behaviors of MSM and changes in incidence of male rectal
      gonorrhea. This report describes the findings of these analyses, which indicate
      increases in unsafe sexual behavior and increases in rates of rectal gonorrhea
      among MSM.

PMID- 9935142
TI  - Outbreak of Vibrio parahaemolyticus infection associated with eating raw oysters
      and clams harvested from Long Island Sound--Connecticut, New Jersey, and New
      York, 1998.
AB  - During July-September 1998, an outbreak of Vibrio parahaemolyticus infections
      associated with consumption of oysters and clams harvested from Long Island Sound
      occurred among residents of Connecticut, New Jersey, and New York. This is the
      first reported outbreak of V. parahaemolyticus linked to consumption of shellfish
      harvested from New York waters. This report summarizes the investigation of this
      outbreak.

PMID- 9935143
TI  - HIV testing--United States, 1996.
AB  - Human immunodeficiency virus (HIV) infection is one of the leading causes of
      morbidity and mortality in the United States. HIV testing, in conjunction with
      counseling and other preventive services, can reduce the risk for HIV infection
      and appropriately link infected persons to treatment. To characterize HIV testing
      by region, state, and sex, CDC analyzed data from the 1996 Behavioral Risk Factor
      Surveillance System (BRFSS). This report summarizes the results of that analysis,
      which indicate a high degree of variability in HIV testing throughout the United
      States.

PMID- 9935144
TI  - Evaluation of varicella reporting to the National Notifiable Disease Surveillance
      System--United States, 1972-1997.
AB  - Varicella (chickenpox) is a common, highly infectious, vaccine-preventable
      disease. Before 1995, an estimated 4 million cases of varicella occurred each
      year in the United States, approximately 100 patients died, and approximately
      10,000 persons were hospitalized because of varicella and related complications.
      Approximately 95% of cases, 66% of hospitalizations, and 45% of the varicella
      related deaths occurred among persons aged <20 years (CDC, unpublished data,
      1998). In 1972, varicella became nationally notifiable in the United States;
      subsequently, 46 states and the District of Columbia (DC) provided weekly reports
      to CDC's National Notifiable Disease Surveillance System (NNDSS). In 1981,
      varicella was deleted from the weekly morbidity report, and in 1982, states were
      encouraged to report varicella to NNDSS annually. In 1995, a live, attenuated
      varicella vaccine was licensed in the United States for routine use in children.
      This report describes changes in the annual reported incidence of varicella from
      1972 to 1997 and discusses the need for increased surveillance with the
      availability of a vaccine.

PMID- 9935145
TI  - A survey of seroprevalence of human papillomavirus types 16, 18 and 33 among
      children.
AB  - The importance and natural history of HPV infections in childhood is incompletely
      understood. We performed a survey for presence of serum antibodies to HPV capsids
      among 1031 children aged 0 to 13 years, resident in Stockholm, Sweden. The HPV
      seroprevalence among these children was 3.0% for HPV16, 0.6% for HPV18 and 2.7%
      for HPV33. By comparison, among simultaneously analyzed positive control panels
      comprising women with CIN or healthy women with type-specific cervical HPV DNA,
      seroprevalence of HPV 16, 18 and 33 was 69%, 58% and 63% respectively. The
      results suggest that HPV infection in childhood is not common.

PMID- 9935146
TI  - Insulin-like growth factor-I and binding protein-3 in relation to childhood
      leukaemia.
AB  - The aetiology of most cases of childhood leukaemia remains unknown, but several
      studies have indicated that increased birthweight and height are risk factors for
      the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of
      growth hormone and has been positively associated with prostate cancer, we have
      evaluated the role of this hormone and its principal binding protein, IGFBP-3, in
      the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from
      those recorded by a national network of childhood oncologists were enrolled in
      our study. Controls were children hospitalised for acute conditions of no more
      than moderate severity with matching for gender, age and maternal place of
      residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using
      commercially available radioimmunoassays. Serum IGF-I values decreased by about
      1.7% per month, and the rate of decline was higher, though not significantly so,
      among cases (2.1% per month) than among controls (1.4%). There was no significant
      association between IGF-I and the likelihood of childhood leukaemia, but an
      increment of 1 microg/ml of IGFBP-3 was associated with a substantial and
      statistically significant reduction of childhood leukaemia by 28% (95% confidence
      interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we
      interpret our findings as indicating that bioavailable IGF-I may play an
      important role in the aetiology of childhood leukaemia. The much smaller
      quantities and the inherent instability of IGF-I in the blood in comparison to
      those of IGFBP-3 are likely to hinder documentation of an underlying positive
      association of IGF-I with the disease.

PMID- 9935148
TI  - Frequent aberration of the transforming growth factor-beta receptor II gene in
      cell lines but no apparent mutation in pre-invasive and invasive carcinomas of
      the uterine cervix.
AB  - The type II transforming growth factor-beta (TGF-beta) receptor (RII) gene
      located at 3p22 plays an important role in regulating growth and differentiation
      of epithelium, including that of the uterine cervix. Loss-of-function mutations
      of RII have frequently been found in gastrointestinal cancers, with a replication
      error (RER) phenotype characterized by the presence of microsatellite instability
      (MI). In this study, genomic PCR, SSCP and DNA sequencing were conducted to
      investigate the coding sequences of the RII gene in cell lines (n = 5) and
      tissues (n = 15) of squamous carcinomas of the uterine cervix. Intragenic
      deletions were noted in 2 of 5 cervical-cancer cell lines (ME180 and HeLa cells).
      However, no mutation, other than DNA polymorphisms, was found in 15 cervical
      cancers with either alleleic loss at 3p22 (n = 11) or MI (n = 4). Further
      analysis of squamous intraepithelial lesions (SIL) with (n = 12) or without (n =
      4) MI for the (A)10 change, a prototypic mutation found in over 90% of RER
      positive colon cancers, also showed no aberration. Our study concludes that the
      RII gene is frequently disrupted in cervical-cancer cell lines, but is rarely
      mutated in CC and SIL tissues, including those showing MI or alleleic loss at
      3p22. The underlined mechanism of genomic instability in CC and SIL may thus
      differ from that of colorectal cancer. The allelic loss at 3p22-24 in CC does not
      involve the coding sequence of the RII gene. The non-coding sequence of RII or an
      unidentified gene may be responsible for it.

PMID- 9935147
TI  - Expression of mutated hepatitis B virus X genes in human hepatocellular
      carcinomas.
AB  - To explore the role of hepatitis B virus (HBV) X protein in liver carcinogenesis,
      independently from its role in viral replication, we have analyzed X gene
      structure and expression in tumorous and non-tumorous tissues obtained from 9
      hepatitis B surface antigen (HBsAg)-negative, HBV DNA-positive patients. HBV
      replication was undetectable in tumorous tissues. HBV X gene was truncated at its
      3' end in 5 of 9 tumorous tissues and 1 of 8 non-tumorous livers. Sequence
      analysis performed on uninterrupted X genes from 3 tumors and 3 surrounding non
      tumorous tissues showed a high rate of mutations, selectively in the tumorous
      livers. In 1 of the 3 tumors, a frameshift mutation induced a new stop at codon
      129. HBV RNAs were tested by reverse transcriptase-polymerase chain reaction (RT
      PCR) with surface (S), core (C) and X specific primers. X, but not S and C, RNA
      expression was found in 6 of 8 tumors and in 6 of 7 non-tumorous tissues. This
      finding was consistent with immunohistochemical detection of X, but not S and C,
      antigens in all tumors also expressing X RNA. Our results provide evidence for
      selective expression of HBV X, but not S and C, RNA and protein in the tumorous
      and non-tumorous tissue of HBsAg-negative, HBV DNA-positive patients. It also
      shows that the structure of the X gene is modified (interrupted or highly
      mutated) in the majority of tumorous livers. Taken together, our findings are
      consistent with a potential role of mutated X proteins in HBV-related liver
      oncogenesis.

PMID- 9935149
TI  - Second primary cancers in patients with squamous cell carcinoma of the skin: a
      population-based study in Sweden.
AB  - We studied second primary cancer among 25,947 patients diagnosed with squamous
      cell carcinoma of the skin (SCC) in Sweden between 1958 and 1992. In total, 5,706
      patients developed a second primary cancer at any site, compared with an expected
      number of 2,651 [standardized incidence ratio (SIR) = 2.15; 95% confidence
      interval (CI) = 2.10-2.21]. Men below 60 years of age at diagnosis of SCC had
      higher SIR (2.5; CI = 2.2-2.8) with the highest risk during the first year of
      follow-up (SIR = 9.2; CI = 6.9-12.2). If second primary SCC was excluded, the SIR
      was reduced to 1.30 (CI = 1.25-1.34); the relationships by sex, age and time
      since diagnosis remained similar. For skin cancer, the SIR for second SCC was
      markedly elevated (SIR = 15.6) and the risk of malignant melanoma was elevated 3
      fold. Significantly increased risks were found for most second cancers in
      squamous cell epithelium: lip (SIR = 5.2), respiratory organs (SIR = 1.7),
      esophagus (SIR = 1.5), cervix uteri (SIR = 2.2), and vulva including vagina (SIR
      = 2.3). There was a generally increased risk of almost 2-fold for second cancer
      in hematopoietic or lymphoproliferative tissues. Slightly increased rates (SIR =
      1.0-1.5) were seen for second tumors in digestive tissues. Finally, a high SIR
      (SIR = 5.5) was observed for second primary cancer in salivary glands. In
      conclusion, patients with SCC are at increased risk to develop new primary
      cancer, especially in skin, squamous cell epithelial and tobacco-related tissues.
      Common risk factors among the tumor types might explain our findings, however, an
      intrinsic susceptibility among SCC patients to develop cancer is also possible.

PMID- 9935150
TI  - Elevated expression of eIF4E in confined early breast cancer lesions: possible
      role of hypoxia.
AB  - The translation-initiation factor eIF4E is rate-limiting for protein synthesis,
      and its over-expression results in oncogenic transformation of mammalian cells.
      eIF4E facilitates the synthesis of several powerful tumor angiogenic factors (FGF
      2 and VEGF) by selectively enhancing their translation. In breast carcinomas,
      eIF4E is commonly over-expressed, but the pathology where this elevation is
      initially manifested is presently unknown. To probe whether the elevation of
      eIF4E marks an early stage of cancer development, we focused our research on
      early cancerous lesions. We have analyzed 70 invasive ductal carcinomas (IDCs),
      78 ductal carcinomas in situ (DCIS), 51 benign lesions and 4 model cell lines for
      elevated expression of eIF4E by several different methods: Northern/Western
      blots, immuno-histochemistry and in situ RT-PCR. eIF4E expression was markedly
      increased in IDC and in islets of viable cells in the center of poorly
      vascularized DCIS, which are not easily identifiable by standard histological
      stains. We also show that expression of eIF4E is increased by hypoxia and,
      presumably, in hypoxic areas of these lesions. We propose that clonal expansion
      of cancer cells, permanently over-expressing eIF4E, gives them a critical
      advantage to survive hypoxia and marks the transition toward the vascular phase
      of cancer progression. Hence, eIF4E may be useful in stratifying DCIS lesions
      according to their malignant stage.

PMID- 9935151
TI  - Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal
      cases and controls.
AB  - Leptin reflects the amount of energy stores, regulates energy balance and is
      associated with circulating levels of reproductive hormones and insulin-like
      growth factor-I (IGF-I). Breast cancer has also been associated with obesity,
      reproductive hormones and circulating IGF-I levels. To determine whether leptin
      is involved in the etiology of breast cancer, we compared serum leptin levels in
      83 cases of pre-menopausal carcinoma in situ of the breast and 69 healthy
      controls recruited in Massachusetts. Serum leptin levels were 13.69 + 1.3 ng/ml
      in cases and 16.03 + 1.7 ng/ml in controls. Data were also analyzed using
      multiple logistic regression with adjustment for known risk factors for the
      development of breast cancer as well as anthropometric, demographic and hormonal
      variables, including estradiol, prolactin, IGF-I and IGF-binding protein-3. Odds
      ratios were 1.75 (95% CI, 0.73-4.21) for the second control-defined tertile and
      1.54 (0.46-5.16) for the third control-defined tertile relative to the first.
      Thus, leptin does not appear to increase the risk of pre-menopausal breast cancer
      in situ substantially.

PMID- 9935152
TI  - Reduction of syndecan-1 mRNA in cervical-carcinoma cells is involved with the 3'
      untranslated region.
AB  - Syndecan-1 is a transmembrane proteoglycan expressed predominantly in epithelial
      cells. Studies with immunohistochemistry have shown that syndecan-1 expression is
      reduced in carcinoma derived from human epidermis. Here we show that syndecan-1
      mRNA, which is abundant in human primary keratinocyte (HK) and HaCaT spontaneous
      immortalized keratinocyte, is decreased in cervical-carcinoma cell lines.
      Further, in relation to a long and well-conserved 3' untranslated region (3' UTR)
      of syndecan-1 cDNA, we examined whether 3' UTR is involved with syndecan-1-mRNA
      reduction in cervical-carcinoma cells. A stable transfection experiment showed
      that addition of the 3' UTR does not affect expression in HaCaT, but that
      syndecan-1 cDNA containing the 3' UTR is not expressed efficiently selectively in
      cervical-carcinoma cell lines. The transient assay with CAT reporter plasmids
      linking the 3' UTR confirmed this, and indicated that the 3' end of the 3' UTR
      (nt 2285-2410) is required to influence expression in cervical-carcinoma cells.
      Further excessive expression of syndecan-1 suppressed growth in cervical
      carcinoma cells. These results demonstrate that the reduction of syndecan-1 mRNA
      involved with the 3' untranslated region gives growth advantage to cervical
      carcinoma cells.

PMID- 9935153
TI  - Cloning of the human uroplakin 1B cDNA and analysis of its expression in
      urothelial-tumor cell lines and bladder-carcinoma tissue.
AB  - The human uroplakin 1B (UPK1B) gene codes for a structural protein which is a
      terminal differentiation component of the asymmetric unit membrane on the apical
      surface of the mammalian bladder. UPK1B is a member of the tetraspan family of
      proteins, many of which have de-regulated patterns of expression in cancer. Using
      polymerase-chain-reaction techniques, we have cloned a partial human UPK1B cDNA
      which codes for the putative full open reading frame for the UPK1B protein. The
      deduced human UPK1B protein sequence has 92% and 93% amino-acid homology with
      bovine UPK1b and mink TI1 proteins respectively. Using Northern analysis, we show
      that the human UPK1B gene is highly expressed in normal human urothelium.
      However, expression of UPK1B mRNA was undetectable or markedly reduced in 11 out
      of 16 samples of transitional-cell-bladder-carcinoma tissue and in all 5 bladder
      carcinoma cell lines when compared with normal urothelial tissue. The molecular
      mechanism of down-regulation of RNA expression does not appear to involve gross
      gene rearrangements or allelic loss.

PMID- 9935154
TI  - Comparison of DNA-adduct and tissue-available dose levels of MeIQx in human and
      rodent colon following administration of a very low dose.
AB  - [2-14C]2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was administered
      orally (304 ng/kg body-weight dose based upon an average 70-kg-body-weight
      subject) to 5 human colon-cancer patients (58 to 84 years old), as well as to
      F344 rats and B6C3F1 mice. Colon tissue was collected from the human subjects at
      surgery and from the rodents 3.5 to 6 hr after administration. Colon DNA-adduct
      levels and tissue available doses were measured by accelerator mass spectrometry
      (AMS). The mean levels of MeIQx in the histologically normal colon tissue were
      not different among the human (97 +/- 26 pg MeIQx/g), rat (133 +/- 15 pg/g) or
      mouse (78 +/- 10 pg/g) tissues; and no difference existed between the levels
      detected in human normal and tumor tissue (101 +/- 15 pg/g). Mean DNA-adduct
      levels in normal human colon (26 +/- 4 adducts/10(12) nucleotides) were
      significantly greater (p < 0.01) than in rats (17.1 +/- 1 adduct/10(12)
      nucleotides) or mice (20.6 +/- 0.9 adduct/10(12) nucleotides). No difference
      existed in adduct levels between normal and tumor tissue in humans. These results
      show that MeIQx forms DNA adducts in human colon at low dose, and that the human
      colon may be more sensitive to the effects of MeIQx than that of mice or rats.

PMID- 9935155
TI  - Selective increase of alpha2-integrin sub-unit expression on human carcinoma
      cells upon EGF-receptor activation.
AB  - The effects of chronic EGF exposure on expression of the alpha2beta1 collagen and
      alpha5beta1 fibronectin receptor in a pair of human carcinoma cell lines (A431
      and A549) with differential responses to EGF in a short-term ECM-cell adhesion
      assay were investigated. Treatment with EGF at 10 ng/ml for 24 hr increased on
      both cell lines the expression of the alpha2- but not the beta1- or alpha5
      integrin sub-units, and concomitantly cellular adhesion was increased on collagen
      IV but not on fibronectin. Increased collagen adhesion of A549 cells could be
      blocked by alpha2- and beta1-integrin-sub-unit antibodies down to control levels,
      while it was blocked by alpha2-integrin-sub-unit antibody only by 60% and
      completely by the beta1-integrin-sub-unit antibody on A431 cells. EGF induced
      disparate shifts in cell morphologies (dome-like structures, A431, vs. spindle
      like fibroblastoid, A549) with concomitant opposite changes in the
      expression/localization of E-cadherin in cell-cell contacts. This could be taken
      as an indication for cell-type-specific differential changes in the ratio of cell
      ECM vs. cell-cell contacts. The EGF-induced up-regulation of the alpha2beta1
      integrin was instrumental in increasing collagen adhesion of A549 but only partly
      in the case of A431 cells, in which cells the alpha2beta1 integrin may have
      additional functions besides serving as cell-ECM receptor.

PMID- 9935156
TI  - Growth inhibition of human pancreatic cancer cell lines by anti-sense
      oligonucleotides specific to mutated K-ras genes.
AB  - About 90% of human pancreatic cancers carry K-ras point mutation, which may play
      an important role in tumorigenesis. We investigated the inhibitory effects of
      anti-sense oligonucleotides targeting K-ras point mutation on the growth of
      cultured human pancreatic cancer cells. Eight human pancreatic cancer cell lines
      were screened for K-ras codon 12 point mutations by PCR-RFLP analysis and direct
      sequencing. Then, 3 cell lines with the major types of K-ras point mutation,
      i.e.,HuP-T1, HuP-T3 and PANC-1, and 1 without mutation, BxPC-3, were used for the
      experiments. Seventeen mer anti-sense oligonucleotides were designed, targeting
      the point mutation of K-ras codon 12, and transfected into the cells by the
      liposome-mediated method. Cell-growth activities were estimated by MTT assay.
      Levels of K-ras mRNA expression were determined using quantitative RT-PCR, and K
      ras p21 protein synthesis was evaluated with Western blotting. Mutation-matched
      anti-sense oligonucleotides effectively inhibited the growth of these pancreatic
      cancer cell lines, except for BxPC-3, by suppressing K-ras mRNA expression and K
      ras p21 protein synthesis. Moreover, mutation-matched anti-sense oligonucleotides
      showed stronger anti-proliferative effects than did mutation-mismatched ones. Our
      results suggest that anti-sense therapy specific to point mutations of K-ras mRNA
      is a practical approach to selective suppression of tumor growth, with little
      effect on normal cells.

PMID- 9935157
TI  - 111Indium-labeled monoclonal antibody K1: biodistribution study in nude mice
      bearing a human carcinoma xenograft expressing mesothelin.
AB  - The monoclonal antibody (MAb) K1 is a murine IgG1 that recognizes mesothelin, a
      differentiation antigen present on mesothelium which is highly expressed on
      cancers derived from mesothelium, including most ovarian cancers and epithelioid
      mesotheliomas. MAb K1 was conjugated to 2-(p-isothiocyanatobenzyl)-cyclohexyl-
      diethylenetriaminepentaacetic acid and labeled with 111In. The biodistribution of
      111In-K1 was studied in athymic nude mice bearing 2 s.c. tumors, one expressing a
      stably transfected plasmid encoding mesothelin and one composed of the parental
      untransfected A431 epidermoid carcinoma cells which do not express mesothelin.
      Tumor-bearing mice were given an i.v. injection of 111In-K1 and killed at
      different time points to determine the uptake of radiolabeled antibody.
      Significantly higher uptake was seen in antigen-positive tumors at all time
      points, with peak values at 72 hr (52.9% vs. 8% of the injected dose/g tissue for
      antigen-positive and antigen-negative tumors, respectively). Uptake in antigen
      positive tumors was higher than the blood level at all time points, and the
      tumors contained a high level of the radiolabeled MAb even at 7 days (28.6% of
      the injected dose/g tumor).

PMID- 9935158
TI  - Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in squamous-cell
      carcinoma by interferon-gamma and cisplatin.
AB  - CD95 (Apo-1/Fas) ligand (CD95L) expression has been observed in various
      malignancies. In human primary cell lines from a squamous cell carcinoma (SCC) of
      the vulva, the effect of cisplatin (CDDP) and IFNgamma on the expression of CD95L
      and its 2 receptor isoforms, CD95 transmembrane (CD95tm) and CD95 soluble
      receptor, was studied at the mRNA and protein levels. Addition of CDDP and
      IFNgamma increased CD95L mRNA levels in the primary cell line 6-fold and 1.7
      fold, respectively. In comparison, CD95tm mRNA levels were diminished by CDDP but
      increased 8-fold upon IFNgamma challenge. CD95L expressed by SCC cells was
      functionally relevant since these cells were able to induce CD95-specific
      apoptosis in autologous lymphocytes from the SCC-bearing patient. Thus, CD95L
      expression in SCC may contribute to tumor-associated immunosuppression, which may
      be modulated by CDDP and IFNgamma. In tumor samples of the primary SCC, CD95L
      expression was enhanced in the area of the border between invasive tumor tissue
      and surrounding stroma cells. The locally restricted over-expression of CD95L was
      congruent with the arrangement of apoptotic stroma cells in the direct vicinity
      of invading tumor tongues, suggesting a role as invasion factor for CD95L.

PMID- 9935159
TI  - HLA-B down-regulation in human melanoma is mediated by sequences located
      downstream of the transcription-initiation site.
AB  - Major histocompatibility complex (MHC, HLA in humans) class I molecules play an
      important role in cellular immunology by presenting viral, tumor-associated or
      minor histocompatibility antigen-derived peptides to T cells. Tumor cells
      frequently fail to express one or more of the different MHC class I loci (HLA-A, 
      B and -C), thereby avoiding elimination by T cells. In primary human melanomas as
      well as melanoma cell lines, HLA class I expression is frequently down-regulated
      in a B locus-specific manner. The HLA class I promoter contains a number of cis
      regulatory elements located upstream of the transcription-initiation site, among
      them enhancer A and an interferon-stimulated response element. In the present
      study, we show that novel sequences located 13 to 33 bp downstream of the
      transcription-initiation site mediate HLA-B locus-specific down-regulation in
      human melanoma cell lines. Furthermore, involvement of the +13 to +33-bp region
      in HLA-B locus-specific down-regulation in vivo is supported by in vitro
      experiments showing locus-specific binding of protein complexes to the +13 to +33
      bp region.

PMID- 9935160
TI  - Redundancy of autocrine loops in human osteosarcoma cells.
AB  - With the aim of identifying innovative therapeutic strategies for osteosarcoma
      patients who are refractory to conventional chemotherapy, we analyzed the in
      vitro effects of the blockage of autocrine circuits. Since the insulin-like
      growth factor-I receptor (IGF-IR)-mediated loop is relevant to the growth of
      osteosarcoma, we analyzed the activity of the IGF-IR-blocking antibody alphaIR3
      in both sensitive and multidrug-resistant osteosarcoma cell lines. Only limited
      effects, however, were observed, suggesting the simultaneous existence of other
      autocrine circuits. Indeed, in a representative panel of 12 human osteosarcoma
      cell lines, in addition to the IGF-IR-mediated circuit, we demonstrated also a
      loop mediated by epidermal growth factor receptor as well as the presence of
      nerve growth factor, low-affinity nerve growth factor receptor as well as
      tyrosine receptor kinase A in the great majority of osteosarcomas. Therapies
      based on the inhibition of single circuits may have only limited effects in
      osteosarcoma, whereas the use of suramin, a drug which, besides other activities,
      non-selectively interferes with the binding of growth factors to their receptors,
      appears as a promising alternative, in both sensitive and drug-resistant
      osteosarcoma cells.

PMID- 9935161
TI  - EGF-related peptides are involved in the proliferation and survival of MDA-MB-468
      human breast carcinoma cells.
AB  - A majority of human breast carcinomas co-express the epidermal growth factor
      (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor
      alpha (TGF-alpha). MDA-MB-468 breast carcinoma cells express CR, AR and TGFalpha,
      while SK-BR-3 cells express CR and TGF-alpha. Anti-sense phosphorothioate
      oligodeoxynucleotides (AS S-oligos) directed against either CR or TGF-alpha
      inhibit the proliferation of both cell lines. A 40-50% growth inhibition was
      observed at a 2-microM concentration of each AS S-oligo. Treatment with the AR AS
      S-oligo also resulted in a significant inhibition of MDA-MB-468 anchorage
      dependent growth (ADG). No significant growth inhibition was observed when MDA-MB
      468 or SK-BR-3 cells were treated with a mis-sense S-oligo. The AS S-oligos
      inhibited the expression of AR, CR or TGF-alpha proteins and mRNAs, as assessed
      by immuno-cytochemistry and semi-quantitative RT-PCR. An additive growth
      inhibitory effect was observed when MDA-MB-468 cells were treated with a
      combination of EGF-related AS S-oligos. Indeed, treatment of MDA-MB-468 cells
      with a combination of AR, CR and TGF-alpha AS S-oligos resulted in about 70%
      growth inhibition at a concentration of 0.7 microM each. Finally, treatment of
      MDA-MB-468 cells with a combination either of the 3 AS S-oligos or of an EGF
      receptor-blocking antibody (MAb 225) and either CR, AR or TGFalpha AS S-oligos
      resulted in a significant increase in DNA fragmentation. Our data suggest that
      the EGF-related peptides are involved in the proliferation and survival of breast
      carcinoma cells.

PMID- 9935162
TI  - Passively transferred anti-MUC1 antibodies cause neither autoimmune disorders nor
      immunity against transplanted tumors in MUC1 transgenic mice.
AB  - C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to
      investigate the autoimmune consequences of producing MUC1 tumor immunity in an
      animal that expresses MUC1 as a self-protein on normal ductal epithelia. Previous
      work showed that MUC1.Tg mice challenged with MUC1-bearing syngeneic tumors
      (B16.MUC1) developed progressively growing MUC1-expressing tumors and no
      detectable MUC1-specific antibody (Ab) response. In contrast, wild-type C57BL/6
      (wt) mice developed MUC1-negative tumors at a significantly slower rate and
      produced approximately 50 microg IgG1 Ab reactive with the MUC1 tandem repeat
      (TR)/ml of sera. One milliliter of these sera was administered passively to
      MUC1.Tg or wt mice and the concentration of the MUC1 TR-reactive IgG1 Abs was
      monitored over time. The results indicate that circulating MUC1-reactive Abs were
      detectable in MUC1.Tg mice and that significant amounts of these Abs were not
      absorbed by organs that endogenously express MUC1. No evidence of autoimmune
      disease, either gross or histological, was observed in the MUC1.Tg recipients of
      sera suggesting that MUC1, an organ-specific protein expressed primarily by
      secretory epithelia, is inaccessible to circulating MUC1 -reactive Abs.
      Additional studies showed that polyclonal sera containing IgG1 Abs reactive with
      MUC1 TR were unable to provide protection against the growth of syngeneic tumors
      expressing MUC1 in the MUC1.Tg animal model.

PMID- 9935163
TI  - Ectopic expression of RET results in microphthalmia and tumors in the retinal
      pigment epithelium.
AB  - The retinal pigment epithelium (RPE) is essential for eye development by
      interacting with the overlaying neuroepithelium. Regulatory sequences of the gene
      encoding for tyrosinase-related protein 1 (TRP-1), linked to the lacZ reporter
      gene, lead to strong and specific beta-galactosidase expression in the RPE. We
      asked how the oncogene ret would affect this epithelial cell type during mouse
      development. We used the TRP-1 promoter to express ret in the developing RPE, and
      obtained transgenic mouse lines, which showed mild to severe microphthalmia.
      During development, the RPE changed to a stratified epithelium with reduced or
      absent pigmentation from E10.5 onward. In addition, proliferation of RPE cells
      and tumor formation were observed from E12.5 onward. These early events prevent
      closure of choroid fissure and lead to microphthalmia and secondary malformations
      after birth. We conclude that ret transgene expression in the RPE prevents normal
      differentiation of this epithelial layer and induces proliferation and tumor
      formation. The appearance of the microphthalmic phenotype underlines the
      requirement of a normally developed RPE for eye development.

PMID- 9935164
TI  - Increased tumorigenicity of rat colon carcinoma cells after alpha1,2
      fucosyltransferase FTA anti-sense cDNA transfection.
AB  - Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H
      increases tumor cell motility and tumorigenesis. Alpha1,2-fucosylation is a key
      step in the synthesis of these antigens. Two alpha1,2-fucosyltransferases,
      expressed in colorectal carcinomas, have been characterized (FUT1 and FUT2 in
      humans, FTA and FTB in rats). To define the relative contribution of each of
      these enzymes in tumor cell behavior, we have used an anti-sense transfection
      approach in rat colon carcinoma PROb cells, which synthesize mRNA encoding for
      both enzymes. We have previously reported that anti-sense transfection of a cDNA
      fragment of the FTB enzyme decreased H antigenic cell-surface levels and
      concomitantly decreased tumorigenicity. H antigens, detected by antibodies
      specific for H type 1, 3 or 4, were detected only on a splice variant of CD44
      containing the product of exon v6. We now report the anti-sense transfection of
      an FTA cDNA fragment into PROb cells, which resulted in decreased enzymatic
      activity on a type 2 precursor and decreased cell-surface H type 2 antigen
      exclusively. Compared to controls, FTA anti-sense-transfected cells were
      significantly more tumorigenic in syngeneic animals but not in immunodeficient
      SCID mice. The UEA-I lectin, specific for H type 2, revealed that these
      structures were present on the CD44v6 variant and on an uncharacterized 80-kDa
      glycoprotein. Our results indicate that FTA and FTB fucosylate distinct glycan
      chains in the same cell, leading to opposite effects, under control of the immune
      system.

PMID- 9935165
TI  - Role of target antigen in bispecific-antibody-mediated killing of human
      glioblastoma cells: a pre-clinical study.
AB  - Bispecific antibodies (bsAbs) directed to tumor-associated antigens and to
      receptors mediating T-cell activation, such as the TCR/CD3 complex and the co
      stimulatory CD28 molecule, are capable of activating T cells at the surface of
      tumor cells, resulting in tumor-cell killing. Here we report the pre-clinical
      characterization of bispecific-antibody fragments (bsFab2) directed to 2
      different glioblastoma-associated antigens: the EGF receptor (EGFR) and a
      chondroitin-sulfate proteoglycan (CSPG). Using cultured glioblastoma cells
      expressing both target antigens, we found that the ability of anti-tumor x anti
      CD28 bsFab2 to mediate "targeted T-cell co-stimulation" is superior for
      constructs targeting the CSPG molecule, correlating with an approximately 6-fold
      higher expression level of this antigen on the cell surface. In contrast, bsFab2
      triggering CD3 are more effective if they contain EGFR-target specificity. This
      indicates that the activity of anti-tumor x anti-CD3 constructs critically
      depends on properties of the antigen other than its expression level on the cell
      surface, e.g., its mobility in the membrane. These findings prompted us to use
      EGFR-targeting bsFab2 in an ongoing clinical trial with glioma patients.

PMID- 9935166
TI  - Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of
      urokinase receptor expression.
AB  - Tumor hypoxia and high levels of expression of the urokinase-type plasminogen
      activator (uPA) receptor (uPAR) represent a poor clinical outcome for patients
      with various cancers. Here, we examined the effect of hypoxia on in vitro
      invasion of extracellular matrix and uPAR expression by human carcinoma cells.
      Compared with culture under 20% O2, culture for up to 24 hr under 1% or 4% O2
      resulted in increased cell surface uPAR. However, the highest uPAR levels were
      observed in cells cultured under 1% O2. Culture of MDA-MB-231 breast carcinoma
      cells under hypoxia also resulted in increased uPAR mRNA levels. Furthermore,
      incubation with cobalt chloride or with an iron chelator also resulted in
      elevated uPAR expression, while presence of 30% carbon monoxide in the hypoxic
      atmosphere reduced the hypoxia-mediated uPAR mRNA upregulation. Increased uPAR
      expression was paralleled by higher cell-associated uPA levels and lower levels
      of secreted uPA as determined by gel zymography performed on cell extracts and
      culture-conditioned media. In addition, the in vitro invasiveness of MDA-MB-231
      breast carcinoma cells was significantly higher when the invasion assay was
      performed under hypoxic conditions. This effect of hypoxia on invasion was
      abrogated by including in the assay a monoclonal, function-blocking anti-u PAR
      antibody or by the presence of 30% carbon monoxide in the hypoxic atmosphere. Our
      findings indicate that hypoxia stimulates carcinoma cell invasiveness by
      upregulating uPAR expression on the cell surface through a mechanism that
      requires a putative heme protein. Through a similar mechanism, hypoxia may
      stimulate tumor invasion and metastasis in vivo.

PMID- 9935167
TI  - Interleukin-10 gene transfer activates interferon-gamma and the interferon-gamma
      inducible genes Gbp-1/Mag-1 and Mig-1 in mammary tumors.
AB  - Expression of IL-10 as a transgene inhibits murine mammary tumor growth and
      metastasis. Using differential display methodology, we sought genes whose
      expression was modulated by IL-10. We compared mRNA isolated from parental murine
      mammary 66.1 tumors, as well as tumors derived from neo(r)-transfected cells and
      6 different IL-10-expressing cell lines. We identified 2 cDNA products that were
      up-regulated in all 6 IL-10-expressing tumors in comparison to parental and 66
      neo tumors. One cDNA corresponds to the murine guanylate-binding protein gene Gbp
      1/Mag-1. The other cDNA corresponds to the chemokine Mig-1 (monokine induced by
      IFN-gamma). Both genes were originally identified in IFN-gamma-activated
      macrophages or macrophage cell lines. We now report that cultured mammary
      epithelial tumor cell lines also express both genes in response to treatment with
      IFN-gamma and LPS. Furthermore, IFN-gamma mRNA is elevated in IL-10-expressing
      tumors in comparison with parental or neo-transfected tumors. Thus, high-level
      expression of IL-10 as a transgene results in activation rather than suppression
      of IFN-gamma as well as 2 IFN-gamma-inducible genes. Up-regulation of host IFN
      gamma is critical to anti-tumor activity since IL-10 no longer inhibits tumor
      growth in hosts with a deletion in the IFN-gamma gene. Additionally, Gbp-1/Mag-1
      and Mig-1 gene induction no longer occur in IFN-gamma mutant mice.

PMID- 9935168
TI  - Wild-type sequence of MYCN in neuroblastoma cell lines.

PMID- 9935169
TI  - Common delta2 and delta8 RB1 variants in human breast and prostate tissues.

PMID- 9935170
TI  - Cancer risk following polyps or cancer of the large bowel in Vaud, Switzerland.

PMID- 9935171
TI  - HPV 16 antibody prevalence in Jamaica and the United States reflects differences
      in cervical cancer rates.
AB  - Human papillomavirus (HPV) is widely accepted as the primary etiologic agent in
      the development of cervical cancer. DNA of a particular HPV type, HPV 16, is
      found in about half of tumors tested. Inconsistent with this causal relationship,
      however, population-based studies of HPV DNA prevalence have often failed to find
      high rates of anogenital HPV infection in countries with high cervical cancer
      rates. To examine this issue, we used serology to compare HPV 16 exposure in
      healthy volunteer blood donors in the United States (n = 278) and similar
      subjects from a country with 3-fold higher cervical cancer rates, Jamaica (n =
      257). Jamaican sexually transmitted disease (STD) patients (n = 831) were also
      studied to examine in detail the relation of HPV 16 antibodies with sexual
      history. Serology was conducted using an ELISA employing HPV 16 virus-like
      particles (VLPs). Age-adjusted seroprevalence rates were greatest among male
      (29%) and female (42%) STD patients, intermediate in male (19%) and female (24%)
      Jamaican blood donors and lowest among male (3%) and female (12%) U.S. blood
      donors. The higher seroprevalence in women was significant, and prevalence tended
      to increase with age. In multivariate logistic regression, controlling for age
      and gender, Jamaican blood donors were 4.2-fold (95% CI 2.4-7.2) and STD patients
      8.1-fold (95% CI 5.0-13.2) more likely to have HPV 16 VLP antibodies than U.S.
      blood donors. Among STD patients, HPV 16 antibodies were associated with lifetime
      number of sex partners and years of sexual activity, as well as other factors.
      Our data suggest that HPV 16 VLP antibodies are strongly associated with sexual
      behavior. Moreover, exposure to HPV 16 appears to be much greater in Jamaica than
      in the United States, consistent with the high rate of cervical cancer in
      Jamaica.

PMID- 9935172
TI  - A high prevalence of p53 mutations in pre-malignant oral erythroplakia.
AB  - Oral squamous-cell carcinoma is thought to be preceded by a number of precursor
      stages which induce morphological changes in cells of the oral mucosa resulting
      in clinically detectable pre-malignant lesions such as erythroplakia or
      leukoplakia. To better understand the etiology of oral erythroplakia, we have
      examined the p53 tumor-suppressor gene (exons 5-9) for mutations in 24 oral
      erythroplakia lesions of varying dysplastic phenotypes by PCR/single-strand
      conformational polymorphism and direct DNA-sequencing analyses. A total of 12 p53
      mutations were detected in 11 of 24 (46%) erythroplakia specimens (one specimen
      contained two different p53 mutations); 25% were single-base-pair deletions and
      33% were either G:C-->T:A transversions or G:C-->A:T transitions. A high
      prevalence of p53 mutation was observed in all categories of erythroplakia
      lesions: 33% for mildly dysplastic lesions, 50% for lesions exhibiting moderate
      to severe dysplasia and 50% for lesions that were carcinoma in situ. Although the
      combined prevalence of p53 mutations observed in erythroplakia was significantly
      higher (p = 0.02) than that observed earlier for leukoplakia, the prevalence of
      p53 mutations was similar in erythroplakia and leukoplakia specimens from
      smokers. The prevalence and spectrum of p53 mutations observed in this series of
      erythroplakia lesions are similar to those observed for oral squamous-cell
      carcinoma. These results indicate that mutations of the p53 gene may be linked to
      the high malignant potential of erythroplakia and provide further evidence that
      p53 mutation may be an early event in the genesis of oral squamous-cell
      carcinoma.

PMID- 9935173
TI  - Effect of body size on breast-cancer risk among Japanese women.
AB  - With the use of data from the hospital-based epidemiologic research program at
      Aichi Cancer Center (HERPACC), the effect of body size on the risk of breast
      cancer was evaluated among Japanese women, who are generally leaner than white
      women. In total, 1,359 breast-cancer cases were included, and 24,207 women,
      confirmed as free of cancer, were recruited as a reference group. Odds ratios
      (OR) and 95% confidence intervals (95% CI) were determined by multiple-logistic
      regression analysis. Separate analyses were performed for pre- and post
      menopausal women. Furthermore, stratification by decade of age was done to
      evaluate the effect of body size on the development of breast cancer. The results
      obtained from the present study were as follows. (1) Current body-mass index
      (BMI) was positively associated with postmenopausal breast cancer (OR 2.08, 95%
      CI 1.49-2.92 for highest quintile vs. lowest), although higher BMI did not affect
      the risk in pre-menopausal women. (2) Estimates of risk were below unity for BMI
      at around age 20 in post-menopausal women. (3) After stratifying BMI at around
      age 20, gaining BMI in later life was positively associated with increased risk,
      regardless of BMI in early life. These findings suggest that avoidance of marked
      weight gain during adult life, especially after natural menopause and/or after
      age 60, may reduce the risk of breast cancer.

PMID- 9935174
TI  - Comparative analysis of Epstein-Barr virus gene polymorphisms in nasal T/NK-cell
      lymphomas and normal nasal tissues: implications on virus strain selection in
      malignancy.
AB  - Whether particular Epstein-Barr virus (EBV) strains are preferentially selected
      in malignant diseases remains controversial. Assessment of the importance of
      strain variation in the pathogenicity of EBV has been hampered principally by the
      lack of accurate data on the prevalence of virus variants in the normal
      population. To clarify this issue, a detailed comparative analysis of the EBV
      genomes contained in normal nasal and nasopharyngeal mucosal tissues and in nasal
      T/NK-cell lymphoma, which originates at these anatomic sites, was carried out by
      PCR amplification across the 30-bp deletion and the 33-bp repeat loci in the LMP1
      gene and the type-specific polymorphic loci in the EBNA2 and EBNA3C genes and by
      sequence analysis of the 3' C-terminal region of the LMP1 gene. Whilst the
      majority of EBV strains in either normal or tumour tissues were type 1 viruses
      with similar numbers of LMP1 repeats, a marked predominance of LMP1 deletion (del
      LMP1) over non-deleted/wild-type LMP1 (wt-LMP1) variants was observed in nasal
      T/NK-cell lymphoma. Although del-LMP1 variants were also prevalent in the normal
      carriers of our population, wt-LMP1 was detected at a significantly higher
      frequency in normal vs. tumour tissues (p = 0.036). More critically, wt-LMP1
      variants were found frequently in mixed infection with del-LMP1 variants in the
      normal carriers. Sequence analysis identified 2 major del-LMP1 (and several wt
      LMP1) variants containing signatory nucleotide changes in relation to the
      prototype B95-8 sequence in both normal and neoplastic nasal tissues. Together,
      our data provide strong evidence for a selection mechanism for del-LMP1 over the
      wt-LMP1 variants in tumours.

PMID- 9935175
TI  - Prospective study on cervical neoplasia IV. Presence of HPV antibodies.
AB  - Sera collected in the course of a prospective study carried out in Prague in 1975
      1983 were assayed for the presence of human papillomavirus (HPV) antibodies.
      Women with cervical neoplasia proven by biopsy at enrollment possessed antibodies
      to peptides derived from E2, E4 and E7 proteins of HPV16 and to virus-like
      particles (VLPs) of HPV16, -18 and -33 significantly more frequently than matched
      controls. Women without cervical neoplasia at enrollment who developed the
      disease in the course of the study differed from matched controls by a higher
      prevalence of antibodies against VLPs of HPV16 and -18 but not against early
      antigens of HPV16. In 19 of the latter subjects, paired serum specimens were
      tested, the first samples having been taken at enrollment and the second at
      diagnosis. Development of the disease was associated with seroconversion from
      negativity to positivity to at least one HPV antigen in 11 (57.9%) women.

PMID- 9935176
TI  - Amplification and over-expression of OZF, a gene encoding a zinc finger protein,
      in human pancreatic carcinomas.
AB  - The OZF gene encodes a protein consisting of 10 zinc finger motifs and is located
      on chromosome 19q3.1. We report here the amplification and over-expression of the
      OZF gene in pancreatic carcinomas. Increased gene copy number was detected in 3
      of 12 tumour cell lines and 2 of 12 primary pancreatic carcinomas. Expression was
      detected in all cell lines, and the gene was over-expressed in cell lines with
      OZF gene amplification. Five of 8 tumours, including 2 primary tumours with OZF
      gene amplification, displayed high levels of OZF protein, whereas normal pancreas
      expressed low levels. Immuno-histochemical analysis showed that expression was
      restricted to tumour cells. Thus, high-level expression of OZF is frequent in
      pancreatic carcinomas and may contribute to the development or progression of
      this tumour.

PMID- 9935177
TI  - MEN1 gene mutation analysis of sporadic adrenocortical lesions.
AB  - To clarify the role of the MEN1 gene in the tumorigenesis of sporadic
      adrenocortical tumors, we performed a molecular study on 35 adrenocortical
      lesions including 6 hyperplasias, 19 adenomas and 10 carcinomas. Loss of
      heterozygosity (LOH) of the MEN1 gene was assessed by PCR using an intragenic
      (D11S4946) and 2 flanking microsatellite markers (D11S4936, PYGM) and/or
      fluorescence in situ hybridization (FISH) with a 40-kb cosmid probe containing
      the MEN1 gene. The complete coding sequence of the MEN1 gene was screened for
      mutations using non-radioactive, PCR-based single-strand conformation
      polymorphism (SSCP) analysis and MDE heteroduplex gel electrophoresis. PCR-LOH
      and FISH analyses performed in 29 tumors (PCR-LOH in 4, FISH in 17 and both in 8
      tumors) revealed allelic deletion of the MEN1 locus in 8 (27.5%) and at 11q13 in
      9 (31%) tumors. Furthermore, the frequency of LOH at 11q13 was significantly
      higher in adrenocortical carcinomas (60%) than in benign lesions (11%). Mutation
      analysis of tumor samples revealed 9 polymorphisms in 7 tumors (S145S, R171Q,
      R171Q together with L432L) but no mutations, with the exception of one
      adrenocortical adenoma. The latter tumor contained a somatic E109X stop codon
      mutation in exon 2 and a 5178-9G-->A splice mutation in intron 4, which was also
      detectable in various nontumorous tissues and blood indicative of a germ-line
      mutation. The patient, who had no clinical signs or family history of MEN1, later
      also developed a neuroendocrine carcinoma (atypical carcinoid) of the lung. Our
      findings indicate that inactivating mutations of the MEN1 tumor-suppressor gene
      appear not to play a prominent role in the development of sporadic hyperplastic
      or neoplastic lesions of the adrenal cortex and that the newly reported 5178-9G-
      >A splice mutation in intron 4 might cause a variant of the MEN1 phenotype.

PMID- 9935178
TI  - Enhancement of tumor killing using a combination of tumor immunization and HSV-tk
      suicide gene therapy.
AB  - Tumor cells genetically modified with the herpes simplex virus thymidine kinase
      (HSV-tk) gene in combination with ganciclovir (GCV) demonstrate a "bystander
      effect". Previous attempts to enhance the bystander tumor killing by combining
      cytokine genes with HSV-tk/GCV have met with varying results. The present study
      was designed to determine the effects of tumor immunization in combination with
      HSV-tk gene-modified tumor cells and GCV on tumor killing and to determine if the
      bystander tumor killing could be enhanced. Tumor-bearing mice immunized with
      syngeneic tumor (KBALB) prior to treatment with an i.p. injection of xenogeneic
      HSV-tk gene-modified tumor cells (PA-1STK) had prolonged animal survival (group
      4, 56.4 days). In contrast, unimmunized tumor-bearing mice (group 2) or tumor
      bearing mice immunized to the xenogeneic PA-1STK tumor cells (group 5) showed a
      mean survival of about 27 days after receiving an i.p. injection of PA-1STK cells
      and GCV. Control groups, which were either not immunized and did not receive HSV
      tk cells (group 1) or immunized but treated only with GCV (group 3) showed short
      survival (16-18 days). Analysis of tumors for cytokine mRNA expression revealed
      increased TNF-alpha and IL-1alpha mRNA expression in group 4 mice. Furthermore,
      IL-2 mRNA expression was detectable on days 2 and 4 only in group 4 mice.
      Immunophenotypic analysis for tumor-infiltrating lymphocytes demonstrated an
      increase in macrophage (4%, p = 0.0001) and T cells (1.8%, p < 0.001) in group 4
      mice with an enhanced T-cell response as compared with mice from groups 1, 2 and
      3. Our results demonstrate that tumor immunization combined with HSV-tk/GCV
      treatment results in increased animal survival with enhanced immune response.
      Furthermore, the cytokine milieu observed in the present study can modulate the
      tumor micro-environment in vivo from one that is immunosuppressive to one that is
      immune-stimulatory.

PMID- 9935179
TI  - Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma
      cells.
AB  - CD44 is a family of cell-surface-adhesion proteins that are thought to play an
      important role in cancer invasion and metastasis. However, the specific
      mechanisms by which CD44 expression modulates invasion or metastasis are not well
      understood. In the current study, we have demonstrated that treatment of human
      melanoma cells with a CD44 MAb, F10-44-2, induces up-regulation of matrix
      metalloproteinase-2 (MMP-2) protein and mRNA. Moreover, treatment of melanoma
      cells with MAb F10-44-2 enhances their migration through gelatin-coated membranes
      and invasion through reconstituted basement membranes. Treatment of melanoma
      cells with several known CD44 ligands, including hyaluronate, extracellular
      matrix proteins, and osteopontin, did not induce MMP-2 production. CD44 binding
      by F10-44-2 MAb results in induction of MMP-2 expression, which is associated
      with enhanced cell migration and invasion. These findings have several
      implications for investigations into tumor metastasis, development, and
      lymphocyte function.

PMID- 9935180
TI  - Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
AB  - The effects of prolonged administration of genistein, a tyrosine-kinase
      inhibitor, on sodium-chloride-enhanced induction of gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic
      indices and vessel counts in the gastric mucosa and gastric cancers, were
      investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats
      were fed chow pellets containing 10% sodium chloride and were given s.c.
      injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every
      other day. In week 52, the incidence of gastric cancers was significantly greater
      in rats fed sodium chloride than in untreated control rats. Prolonged
      administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body
      weight significantly reduced the incidence of gastric cancers, which was
      increased by oral treatment with sodium chloride. Genistein at the higher dose
      significantly decreased the labeling index and vessel counts of the antral mucosa
      and the gastric cancers (which were increased by treatment with sodium chloride)
      and significantly increased the apoptotic index of the antral mucosa and the
      cancers (which was lowered by the treatment with sodium chloride). These findings
      suggest that genistein attenuates gastric carcinogenesis promoted by sodium
      chloride, by inducing increased apoptosis and lower cell proliferation and
      angiogenesis of antral mucosa and gastric cancers.

PMID- 9935181
TI  - Effect of serum starvation on expression and phosphorylation of PKC-alpha and p53
      in V79 cells: implications for cell death.
AB  - The effect of serum starvation on the expression and phosphorylation of PKC-alpha
      and p53 in Chinese hamster V79 cells was investigated. Serum starvation led to
      growth arrest, rounding up of cells and the appearance of new PKC-alpha and p53
      bands on Western blots. Prolonged incubation (> or = 48 hr) in serum-deprived
      medium led to cell detachment and death. Moving cells to fresh medium containing
      10% serum before, but not after, cell detachment reversed the changes observed in
      PKC-alpha and p53, and also prevented later cell detachment. Radiolabelling
      studies showed that the higher-molecular-weight PKC-alpha and p53 bands result
      from increased phosphorylation, while a lower-molecular-weight PKC-alpha band
      reflects newly synthesized protein. Immunocomplex kinase assays have shown that
      the increased phosphorylation of PKC-alpha is associated with its increased
      activity. To study the relationship between PKC-alpha, p53 and cell death, cells
      were treated either with TPA, to down-regulate PKC or with staurosporine, to
      inhibit PKC activity. Staurosporine, a potent PKC inhibitor and inducer of
      programmed cell death, caused the appearance of new PKC-alpha and p53 bands
      similar to those induced by serum starvation. If serum starvation was preceded by
      prolonged (48 hr) TPA treatment to down-regulate PKC-alpha, cell detachment and
      death did not take place within the same time frame. Intracellular fractionation
      of cells demonstrated that increased expression of PKC-alpha and the appearance
      of the associated higher and lower molecular-weight bands occurred in the
      nucleus. These data highlight the association of PKC-alpha and p53 with cellular
      events leading to cell death.

PMID- 9935182
TI  - In vitro invasiveness of human epithelioid-sarcoma cell lines: association with
      cell motility and inverse correlation with the expression of tissue inhibitor of
      metalloproteinases.
AB  - Epithelioid sarcoma (ES) is a very aggressive soft-tissue tumor in vivo, but no
      experimental data on its invasive and metastatic behavior have been reported. In
      the present study, 3 different clonal sub-populations (GRU-1A, GRU-1B and GRU
      1C), derived from the same human ES cell line, GRU-1, were investigated for in
      vitro invasiveness in relation to migration, adhesion and the expression of
      different invasion- and metastasis-related genes. Tumor spheroids of GRU-1A were
      markedly more invasive in the chick-heart invasion assay (CHIA) than spheroids of
      GRU-1B and GRU-1C. These results were paralleled by a significantly higher cell
      motility of GRU-1A than GRU-1B and GRU-1C (p < 0.05) on distinct substrates,
      suggesting that the observed differences in invasion result at least in part from
      differences in motility. When invasion was assayed with suspended tumor cells in
      the Matrigel assay, differences between the 3 cell lines were much more
      pronounced than in the CHIA, where cell-cell contacts are established. These
      results indicate that interclonal differences in ES invasion result mainly from
      differences in motility, but also partly depend on differences in cell-cell
      adhesion. On the molecular level, low invasive potential was associated with over
      expression of distinct tissue inhibitor of metalloproteinases (TIMPs) relative to
      matrix metalloproteinase-2 and -9. However, no association was found between
      invasion and the expression of CD44 splicing variants or nm23 isoforms. Our
      results suggest that differences in invasion between GRU-1A, GRU-1B and GRU-1C
      are caused mainly by interclonal differences in migration, and might result from
      differences in the expression of distinct TIMPs.

PMID- 9935183
TI  - Schedule-dependent interaction of doxorubicin, paclitaxel and gemcitabine in
      human breast cancer cell lines.
AB  - We showed previously that a sequential treatment with doxorubicin (4 hr) followed
      by paclitaxel (24 hr) (Dox-->Pacl) induces a synergistic cytotoxic effect in the
      BRC-230 breast cancer cell line and in human primary breast cancer cultures. The
      validity of this experimental finding was confirmed in a clinical phase I/II
      study on advanced breast cancer patients. To improve the cytotoxic effect
      obtained by the Dox-->Pacl sequence, we analyzed the effect of adding gemcitabine
      (Gem) to the Dox-->Pacl sequence in a preclinical study. Our study was performed
      on BRC-230 and MCF-7 cell lines, and cytotoxic activity was evaluated by the
      sulforhodamine B assay and the type of drug interaction by Drewinko's test. When
      Gem (0.01 microg/ml for 24 hr) was given immediately or 24 hr after Dox-->Pacl,
      an antagonistic cytotoxic effect was observed. Conversely, a synergistic effect
      was found when Gem was given 48 hr after Dox-->Pacl. From results of flow
      cytometric analysis, the synergistic effect was attributed to cell cycle
      perturbation. Cells were arrested in G2-M (95% in treated vs. 21% in control
      samples) 24 hr after Dox-->Pacl treatment. The block progressively recovered
      thereafter, and after a further 24 hr, at the time of Gem treatment, the cells
      progressed into the G1-S phase boundary (the cell cycle phase susceptible to the
      cytocidal effect of the drug). Our findings suggest that the interactions of Dox,
      Pacl and Gem are highly schedule- and time-dependent and should be taken into
      consideration in the planning of clinical protocols.

PMID- 9935184
TI  - JNK/SAPK activity is not sufficient for anticancer therapy-induced apoptosis
      involving CD95-L, TRAIL and TNF-alpha.
AB  - We report here that stress stimuli such as gamma-irradiation or the anticancer
      drug doxorubicin activate expression of the death-inducing ligands (DILs) CD95-L,
      TNF-alpha and TRAIL. Apoptosis induced by gamma-irradiation or doxorubicin
      engages a FADD- and caspase-dependent apoptosis pathway which is inhibited by
      dominant negative FADD or the caspase inhibitor zVAD. zVAD did not prevent
      activity of JNK/SAPKs in response to doxorubicin suggesting that JNK/SAPK
      activity is independent of death receptor triggering during cellular stress
      induced apoptosis. In addition, JNK/SAPKs remained activated by doxorubicin in
      resistant cell lines in which cleavage of caspases and apoptosis was not
      observed. These data uncouple JNK/SAPK activation and apoptosis signaling and
      indicate that cellular stress-induced apoptosis involves signaling via DILs which
      is paralleled by activation of JNK/SAPKs. Activation of these kinases may
      contribute e.g., to the expression of molecules involved in apoptosis but is not
      sufficient for induction of the apoptosis program following cellular stress.

PMID- 9935185
TI  - Anti-tumor activity of interleukin-2-producing tumor cells and recombinant
      interleukin 12 against mouse glioma cells located in the central nervous system.
AB  - Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory
      models. Although IL-12 itself activates strong anti-tumor activity, the
      combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL
      12 has been shown to cure tumor-bearing mice more effectively than either rIL-12
      or IL-2-transduced tumor vaccines alone. In the present study, regression of
      brain tumors established in naive mice was obtained by combined administration of
      an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL
      2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration
      substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas
      located in the brain. Although vaccination with SR/IL-2 cells alone was not
      effective against s.c. inoculated gliomas, the combination therapy of vaccination
      with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12
      alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL
      2 cells and of rIL-12 remarkably prolonged survival as compared with untreated
      mice. Efficacy was reduced when studies were performed in mice depleted of CD8+
      cells or NK cells. Mice cured of their intracerebral tumors by combined
      administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon
      rechallenge. In summary, the therapeutic potential for control of tumor growth by
      intratumoral administration of IL-2-producing glioma cells and rIL-12 may be
      useful in the development of treatment for patients with glioma.

PMID- 9935186
TI  - Activation of the insulin-like growth factor-1 receptor promotes the survival of
      human keratinocytes following ultraviolet B irradiation.
AB  - The ultraviolet B (UVB) component of sunlight causes non-melanoma skin cancers
      due to the damage it inflicts on genomic DNA. The response of epidermal
      keratinocytes to sunlight depends on the dose of UVB received and the severity of
      the damage to the DNA. Mild DNA damage typically induces DNA-repair pathways and
      cell survival, while severe DNA damage provokes apoptosis. Primary human
      keratinocytes grown in serum-free media respond in a similar manner to UVB
      irradiation. However, we observed that keratinocytes are exquisitely more
      susceptible to UVB-induced apoptosis if the growth medium is depleted of
      exogenous growth factors. Therefore, an exogenous growth factor could provide
      protection from UVB-induced apoptosis. We found that the only growth factor that
      provided protection from UVB-induced apoptosis was insulin and that the
      protective effect elicited by insulin was not due to binding the insulin receptor
      but, rather, to activation of the insulin-like growth factor-1 (IGF-1) receptor.
      Additionally, activation of the IGF-1 receptor in combination with UVB
      irradiation induced keratinocytes to become post-mitotic. This survival function
      of the IGF-1 receptor in response to UVB irradiation was influenced by activation
      of phosphatidylinositol-3 kinase and MAP kinase. Prior to UVB irradiation,
      insulin or IGF-1 had little to no effect on cell growth or viability. Therefore,
      activation of the IGF-1 receptor in conjunction with UVB irradiation promotes
      keratinocyte survival at the expense of cell proliferation.

PMID- 9935187
TI  - Down-regulation of CD44 expression in human prostatic carcinoma cell lines is
      correlated with DNA hypermethylation.
AB  - Down-regulation of the cell-surface adhesion molecule CD44 has been suggested to
      play an important role in tumor progression and metastasis of prostate cancer.
      CD44 is encoded by a gene that contains a CpG-rich region (CpG island) in its 5'
      regulatory sequence. We tried to assess whether hypermethylation of this region
      is the mechanism responsible for CD44 transcriptional inactivation. A panel of
      prostatic-carcinoma cell lines, Du145, LNCaP, PC3, PC346C and TSU, was analyzed
      for CD44 mRNA and protein expression. Du145, PC3 and TSU were positive for CD44,
      whereas in LNCaP and PC346C both CD44 mRNA and protein expression was suppressed.
      Methylation-sensitive restriction-enzyme analysis of genomic DNA showed that, in
      contrast to the CD44-positive cell lines, the CD44-negative lines were
      hypermethylated in the CD44 promoter CpG island. Furthermore, treatment of a
      PC346C culture with the demethylating agent 5-azacytidine resulted in re
      expression of CD44 mRNA. It is concluded that hypermethylation of the CD44 5'
      promoter region is one of the mechanisms by which CD44 expression is down
      regulated in prostatic-carcinoma cell lines.

PMID- 9935188
TI  - Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor.
AB  - Induction of lipolysis in murine white adipocytes by a tumour lipid-mobilising
      factor (LMF) was associated with stimulation of adenylate cyclase in adipocyte
      plasma membrane preparations. Induction of lipolysis was attenuated by the
      adenylate cyclase inhibitor MDL12330A and the protein kinase A inhibitor H8,
      suggesting that cAMP was the intracellular mediator of induction. The effect of
      LMF on adenylate cyclase was responsive to GTP, with low concentrations (0.1
      microM) causing stimulation and high concentrations (10 microM) causing
      inhibition, suggesting the involvement of both stimulatory (Gs) and inhibitory
      (Gi) guanine nucleotide-binding proteins. At a concentration of 10 microM,
      propranolol noncompetitively reduced the induction of lipolysis by LMF. Thus,
      lipolysis in white adipose tissue during the process of cancer cachexia is
      mediated by a tumour factor which stimulates cAMP production, possibly through a
      beta-adrenergic receptor.

PMID- 9935189
TI  - Neurotensin and a non-peptide neurotensin receptor antagonist control human colon
      cancer cell growth in cell culture and in cells xenografted into nude mice.
AB  - The intestine is a large endocrine organ, but the dependence of colon cancer on
      hormones remains unknown. We show here that neurotensin, a paracrine/endocrine
      peptide in the gut, and the neurotensin receptor antagonist SR 48692 control
      colon cancer cell growth in vitro and in vivo by interacting with receptors that
      are ectopically expressed in colon cancers. In cell culture, neurotensin
      stimulates the growth of human colon cancer cell lines (SW480, SW620, HT29,
      HCT116 and Cl.19A) expressing the neurotensin receptor NTR1 but does not change
      the growth of Caco2 cells, which do not express NTR1. In SW480 cells, neurotensin
      is active in the 10(-10) to 10(-6) M concentration range (ED50 = 0.47 nM) while
      the neurotensin fragment (I-II) is inactive. Neurotensin also enhances the
      cellular cloning efficiency of SW480 cells in soft agar by inducing a 50%
      increase of colony formation. This effect is blocked by SR 48692, which alone
      does not alter colony formation. Subcutaneous delivery of neurotensin (0.54
      micromol/kg every 24 hr) by osmotic pumps to nude mice that have been xenografted
      with SW480 cells results in a significant increase of tumor volume, i.e., up to
      255% of control at day 20 of treatment. SR 48692 administered alone (1.7
      micromol/kg every 24 hr) by daily i.p. injections reduces the development of
      tumors formed by xenografting SW480 cells in nude mice. A significant mean
      reduction of tumor volume of 38% is observed during the 22-day period of
      treatment. SR 48692 alone is also active at reducing tumor volume after
      xenografting HCT116 cells in nude mice. Our results support the notion that colon
      cancer growth may be dependent on blood-borne neurotensin and suggest that non
      peptide neurotensin antagonists, such as SR 48692, may be useful for the
      development of novel therapeutic strategies of colon cancer.

PMID- 9935190
TI  - Activation of protein kinase C modulates cell-cell and cell-substratum adhesion
      of a human colorectal carcinoma cell line and restores 'normal' epithelial
      morphology.
AB  - Abnormal cell adhesion is an important contributing factor in invasion and
      metastasis. Here, we show that morphologically 'normal' cell-cell and cell
      substratum adhesion can be restored to a poorly differentiated carcinoma cell
      line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as
      multicellular aggregates loosely attached to the substratum. The phorbol ester 12
      O-tetradecanoylphorbol-13-acetate (TPA, 7.5 nM) induces rapid adhesive changes
      with 2 components. First, within 15 min of TPA the cells become closely apposed,
      an event resembling the 'compaction' seen in the mouse early embryo. Next, over 2
      hr, the cells spread, forming a monolayer. We show that compaction depends on
      extracellular calcium, E-cadherin-mediated adhesion and F-actin but not on
      protein synthesis, microtubules or substratum adhesion. By contrast, cell
      spreading is independent of cadherin and extracellular Ca2+ but involves the
      formation of focal contacts containing alpkha(v) integrin. TPA treatment causes
      rapid translocation of PKC-alpha to the insoluble fraction. During compaction,
      actin- and PKC-alpha-containing lamellae form over the entire aggregate surface,
      those adjacent to the substratum appearing to initiate spreading. Compaction does
      not involve increased phosphorylation of the cadherin/catenin complex. We
      conclude that activation of PKC-alpha restores 'normal' morphology to these
      poorly differentiated cells. Our results are of general interest in relation to
      the regulation of cell adhesion and, through further investigation, may lead to
      identification of novel targets for therapeutic suppression of invasion and
      metastasis.

PMID- 9935192
TI  - Hepatocellular carcinoma in an orthotopic mouse model metastasizes
      intrahepatically in cirrhotic but not in normal liver.
AB  - Prognosis of hepatocellular carcinoma (HCC) still remains poor mainly because of
      intrahepatic metastasis. In the majority of cases, HCC is found in conjunction
      with liver cirrhosis. It is, therefore, of great importance to investigate the
      invasive and metastatic behavior of HCC in cirrhotic liver. To examine this, a
      liver cirrhosis model was produced by injecting thioacetamide i.p. into mice.
      Murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI, and
      implanted directly under the capsule of cirrhotic and normal livers of syngeneic
      mice. DiI-labeled HCC cells in the liver were observed under fluorescent and
      confocal microscopy. Histological analysis of cirrhotic and normal livers
      revealed that implanted HCC cells migrated to and invaded the adjacent periportal
      regions, but not the adjacent centrolobular areas. This characteristic behavior
      of HCC was more evident in cirrhotic liver than in normal liver. Furthermore,
      intrahepatic metastasis to unimplanted hepatic lobes was observed in cirrhotic
      liver as early as 7 days after implantation, while it was not detected in normal
      liver even 4 weeks later. Thus, an orthotopic animal model for HCC with cirrhosis
      described here may be suitable for investigating the invasive and metastatic
      behavior of HCC. Importantly, labeling tumor cells with a fluorescent dye before
      orthotopic implantation may be a convenient and useful method to investigate the
      invasive and metastatic behavior of various types of cancer.

PMID- 9935191
TI  - Enhancement of 5-fluorouracil cytotoxicity by human thymidine-phosphorylase
      expression in cancer cells: in vitro and in vivo study.
AB  - Transferring a gene into cancer cells in order to sensitize them to drugs is an
      important approach in human cancer gene-therapy research. Thymidine phosphorylase
      (TP) is the first enzyme in the metabolic activation pathway of 5-fluorouracil (5
      FU) to fluorodeoxyribonucleotides, thus, it could be used to increase the
      sensitivity of cancer cells to this anti-pyrimidine agent. In this study, an
      expression vector containing the human TP cDNA was transfected into C26 murine
      colon-carcinoma cells. Stable transfectants were selected; all showed increased
      TP activity, ranging from 2- to 10-fold when compared with wild-type cells. The
      in vitro sensitivity of transfectants to 5-FU and 5'-deoxy-5-fluorouridine (5'
      DFUR) was enhanced, in agreement with the observed increase in TP activity. Then,
      tumors were generated by s.c. injection of TP-transfected or wild-type C26 cells
      in syngeneic BALB/c mice. 5-FU (25 mg/kg, i.p.) induced a growth delay of TP
      transfected C26 tumors as compared with C26 wild-type tumors. These data suggest
      that TP could be transfected in tumor cells to increase the sensitivity to 5-FU
      for subsequent cancer gene therapy.

PMID- 9935193
TI  - New model of ErbB-2 over-expression in human mammary luminal epithelial cells.
AB  - The ErbB-2 receptor has been strongly implicated in the development of breast
      cancer. To establish a new model system to investigate the role of erbB-2 in
      tumorigenesis of the breast, the conditionally immortalised human mammary luminal
      epithelial cell line HB4a was transfected with erbB-2 cDNA. Biological and
      biochemical characterisation of the resulting cell lines demonstrated that high
      levels of ErbB-2 expression were sufficient to cause transformation in vitro but
      did not cause tumours in vivo. Transformation by overexpression of ErbB-2
      correlated with ligand-independent tyrosine phosphorylation of ErbB-2 and the
      adaptor protein Shc. Over-expression of ErbB-2 also resulted in the ligand
      independent constitutive association between Shc and another adaptor protein,
      Grb2, indicating that receptor activation was sufficient to activate downstream
      signalling pathways. Using the model described, it was found that elevation of
      ErbB-2 expression levels caused marked quantitative and qualitative alterations
      in responses to the ligands epidermal growth factor and heregulin. Data indicate
      a central role for ErbB-2 in mediating the responses induced by these ligands and
      suggest that these altered ligand-dependent responses play an important role in
      tumorigenesis in vivo.

PMID- 9935194
TI  - A MAGE-1-encoded HLA-A24-binding synthetic peptide induces specific anti-tumor
      cytotoxic T lymphocytes.
AB  - Although several MAGE-1 peptides have already been identified, the MAGE-1-encoded
      peptide presented by HLA-A24, which is the most common allele in Japanese
      population and is also frequently present in Caucasians, might have a wide
      applicability for immunotherapy using these peptides. To identify this potential
      peptide, we examined the induction of specific cytotoxic T lymphocytes (CTL) from
      the peripheral-blood mononuclear cells (PBMC) in HLA-A24 healthy donors by in
      vitro stimulation with MAGE-1-encoded synthetic peptides with a binding affinity
      for HLA-A24, by a simplified method. Of the 5 peptides tested, the highest HLA
      binder (NYKHCFPEI) was able to elicit CTL from unseparated PBMC by stimulation
      with freshly isolated, peptide-pulsed PMBC as antigen-presenting cells (APC) and
      by also using interleukin 7 and keyhole-limpet hemocyanin for a primary culture.
      The induced CTL could thus lyse HLA-A24 tumor cells expressing MAGE-1, as well as
      the peptide-pulsed target cells, in an HLA-class-I-restricted manner. By using
      the MAGE-1/HLA-A24 peptide, NYKHCFPEI, we found it possible to immunize many more
      patients, especially Japanese patients, by means of such peptide-based
      immunotherapeutic approaches to MAGE-1-positive malignant tumors.

PMID- 9935195
TI  - Classic Kaposi's sarcoma as a first primary neoplasm.
AB  - Patients with a diagnosis of primary classic Kaposi's sarcoma (CKS) appear to be
      at a higher risk of multiple neoplasms. We analyzed a nation-wide series of 1,016
      patients with a primary CKS occurring between 1961 and 1992 in the Jewish Israeli
      population to evaluate the risk of secondary neoplasms. The primary CKS and
      subsequent neoplasms were identified from the Israel Cancer Registry. All HIV
      seropositive Kaposi's sarcoma cases were excluded. The expected number of second
      primary neoplasms was calculated after stratifying by age, origin and gender. Of
      the CKS patients, 61 developed a second neoplasm by the end of the study, similar
      to the expected number of 60.33 [standardized incidence ratio (SIR) of 1.01].
      However, there was an excess of non-Hodgkin's lymphoma (NHL) (SIR = 3.94) and
      cutaneous malignant melanoma (SIR = 5.81), balanced by a deficit of lung cancers
      (none observed, 7 expected). We found high risk for migrants from Eastern Europe
      when compared with other migrants for both solid tumors [rate ratio (RR) = 3.01]
      and NHL (RR = 4.10). Patients with a diagnosis of primary CKS do not have an
      overall increased risk of new neoplasms later in life. However, an increased risk
      of NHL implies the presence of common risk factors for both NHL and CKS.

PMID- 9935196
TI  - Classic Kaposi's sarcoma as a second primary neoplasm.
AB  - Although the incidence of classic Kaposi's sarcoma (CKS) has been investigated,
      its occurrence following a primary neoplasm and its association with this first
      neoplasm need to be determined. We analyzed a series of 124 patients with a
      secondary CKS (8.4% of a total of 1485 incident cases) which occurred between
      1961 and 1992 in the Jewish Israeli population. Data on first neoplasms and
      subsequent Kaposi's sarcoma were retrieved from the Israel Cancer Registry.
      Acquired-immune-deficiency-syndrome-related Kaposi's sarcomas were excluded from
      the case series. Four controls were randomly selected for each CKS case among all
      Cancer Registry cases free from a second neoplasm at the time of diagnosis of the
      CKS in the case, and matched on gender, year of birth and year of diagnosis of
      the first neoplasm. The average time lapse between first neoplasm and secondary
      CKS was 4.5 years, being shorter for prostate cancer and for hematopoietic
      malignancies. As compared with Israel-born Jews, the risk of a subsequent CKS was
      significantly increased in immigrants [odds ratio (OR) 3.0]; this risk was
      particularly high in immigrants from the former Soviet Union (OR 9.4) and Poland
      (OR 7.0). There was no clear trend with age at immigration; however, low age at
      immigration and a short length of stay in Israel endowed a higher risk of
      developing a secondary CKS, markedly among patients suffering from solid tumors
      as the first primary. There was an excess of secondary CKS following a non
      Hodgkin's lymphoma (OR 5.3), a Hodgkin's lymphoma (OR 7.5), a leukemia (OR 5.3)
      or a breast cancer (OR 2.2). Cancer patients with a first primary in the lung,
      colon, stomach, larynx, liver, pancreas or kidney showed secondary CKS less
      frequently. Despite the lack of control of therapy for the first neoplasm,
      development of secondary CKS seems to be mediated by mechanisms similar to those
      for hematopoietic neoplasms and selected nonhematopoietic neoplasms, such as
      breast cancer. The trend toward increased risk after a short time lapse and the
      difference in risk among immigrants indicate that genetic susceptibility is part
      of the complex interplay between cellular proliferation and control systems.

PMID- 9935197
TI  - Survival of patients with hereditary colorectal cancer: comparison of HNPCC and
      colorectal cancer in FAP patients with sporadic colorectal cancer.
AB  - Conflicting data exist on the prognosis of hereditary colorectal cancer. HNPCC
      patients, in particular, are often reported to have a better survival. We
      examined 2,340 colorectal-cancer patients treated in our Institution: 144 HNPCC
      patients (Amsterdam Criteria), 161 FAP patients and 2,035 patients with sporadic
      cancer. Data on hereditary-cancer patients treated between 1980 and 1995 was
      collected in a registry. The 2,035 sporadic colorectal-cancer patients (controls)
      included all new cases treated in the Department of Gastrointestinal-Tract
      Surgery during the same period. Observed survival was estimated using the Kaplan
      Meier method. Cumulative survival probability was estimated at 5 years within
      each group and stratified by various clinical and pathological variables. The age
      distribution at diagnosis of sporadic patients was significantly higher than that
      of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001). In
      the HNPCC group, 40% had a right cancer location, vs. 14% in the FAP group and
      13% in the sporadic-cancer group. In the sporadic group, 51% were early-stage
      cancers (Dukes A or B) vs. 48.4% and 52.1% in the FAP and HNPCC groups
      respectively. In the HNPCC, FAP and sporadic-cancer groups, the 5-year cumulative
      survival rate was 56.9%, 54.4% and 50.6% respectively. Survival analysis by the
      Cox proportional-hazards method revealed no substantial survival advantage for
      HNPCC and FAP patients compared with the sporadic group, after adjustment for
      age, gender, stage and tumor location. The hazard ratio for HNPCC was 1.01 (95%
      CI 0.72-1.39) and 1.27 (95% CI 0.95-1.7) for FAP patients compared with the
      sporadic-colorectal-cancer group.

PMID- 9935198
TI  - Insulin-like growth factor-I expression in normal and diseased endometrium.
AB  - While the role of steroid hormones in the regulation of endometrial proliferation
      and differentiation is well established, the effects of growth factors and their
      receptors in normal and neoplastic endometrium remain a matter of debate.
      Previous studies have documented the positive effects of insulin-like growth
      factor-I (IGF-I) on epithelial cell proliferation and the active production of
      this growth factor in endometrial tissues. In view of decreased expression of
      transforming growth factor-beta1 (TGF-beta1), an antagonist of IGF-I, in
      endometrial carcinoma, we investigated the expression of IGF-I, at both the mRNA
      and protein levels, and the immunoreactivity for type I IGF-I receptor in 30
      formalin-fixed, paraffin-embedded tissue samples of normal and neoplastic
      endometrium, in order to possibly clarify the role of IGF-I in endometrial
      proliferation and differentiation. Our results demonstrate a reduced expression
      of IGF-I mRNA in endometrial carcinomas compared with non-neoplastic tissues,
      despite equivalent immunohistochemical expression of IGF-I and IGF-I receptor.
      Our data suggest that IGF-I and its corresponding receptor may not be directly
      involved in endometrial cancer cell proliferation and differentiation in vivo,
      though other components of the IGF-I system (e.g., IGF binding proteins) may
      affect endometrial malignant transformation and tumor progression.

PMID- 9935199
TI  - Expression of facilitative glucose transport proteins during development of
      squamous cell carcinomas of the head and neck.
AB  - Positron emission tomography studies on malignant head and neck tumors have shown
      that tumor growth and elevated glucose uptake are associated. On a molecular
      level, glucose uptake is mediated by specific glucose transport proteins, which
      exhibit an altered expression in head and neck malignant neoplasms. However, it
      is unknown when during development of squamous cell carcinomas an alteration of
      the expression of glucose transport proteins occurs. We have studied the
      expression of different facilitating glucose transport proteins (GLUT 1, 2, 3 and
      4) by immunohistochemistry in a variety of preneoplastic and neoplastic mucosal
      lesions of the head and neck. We have observed weak expression of GLUT 1 in
      normal mucosa, a marked expression of GLUT 1 throughout preneoplastic lesions,
      which correlated well with the degree of dysplasia. In squamous cell carcinomas
      of the head and neck (HNSCC) and metastases, GLUT 1 was always expressed
      strongly. In contrast, GLUT 2, 3 and 4 were not detected in any of the epithelial
      tissues examined. The increased expression of GLUT 1 in dysplastic lesions and
      its sustained expression in SCC indicate that changes of GLUT 1 expression are
      early events during development of HNSCC. Therefore, the detection of GLUT 1
      might be a reliable marker in the diagnosis of premalignant lesions of the
      oropharyngeal mucosa.

PMID- 9935200
TI  - CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene
      alterations and mapping of 12q13 amplicons.
AB  - The INK4A gene, localized to human chromosome 9p21, encodes p16INK4A, a tumor
      suppressor that functions at least in part through the inhibition of CDK4, a
      cyclin-dependent kinase encoded by a gene at 12q13. To examine INK4A gene
      alterations in uncultured samples of osteosarcoma and the relationship between
      INK4A and CDK4 alterations, we analyzed the INK4A and CDK4 genes in 87 specimens
      from 79 patients. INK4A deletion and CDK4 gene amplification were determined by
      quantitative Southern blot analysis. INK4A exon 2 was screened for mutation by
      polymerase chain reaction and single-strand conformational polymorphism analysis.
      Methylation at the CpG island in INK4A, associated with loss of p16INK4A
      expression, was assessed by Southern blot analysis using methylation-sensitive
      restriction enzymes. INK4A deletion (4/55) or rearrangement (1/55) was found in 5
      of 55 cases. No INK4A exon 2 point mutations and methylation were detected. CDK4
      gene amplification was found in 6 of 67 samples, but not in tumors with INK4A
      alteration. Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and
      MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent
      targets for amplification, with variable amplification of the intervening region
      containing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4
      amplification, the tumors in 22% contained one or the other. The prevalence of
      these alterations, in conjunction with the reported inactivation of RB in up to
      80% of cases, suggests that genetic lesions deregulating the G1 to S cell cycle
      checkpoint may be an almost constant feature in the pathogenesis of osteosarcoma.

PMID- 9935201
TI  - Identification of two distinct deletion targets at 11q23 in cutaneous malignant
      melanoma.
AB  - Karyotypic and molecular data indicate that genetic alterations of the long arm
      of chromosome 11 (11q) are involved in the pathogenesis of malignant melanoma as
      well as of other malignancies. We have shown previously, by analysis of loss of
      heterozygosity (LOH), that a tumor-suppressor gene playing an important role in
      malignant melanoma is likely to be located within a 51-cM region at 11q23. Its
      loss appeared to be a late event in tumor progression and an indicator of a less
      favorable clinical outcome. To further test this hypothesis on a larger set of
      tumors and to refine the region(s) of common allelic loss, we analyzed 21
      polymorphic microsatellite repeats on 11q. A PCR-based assay for LOH was used to
      study normal and tumor tissues from 53 individuals with primary cutaneous
      malignant melanoma or metastatic disease. Our findings indicate that in cutaneous
      malignant melanoma there are at least 2 distinct regions of common allelic loss
      on 11q, one of them centered around marker APOC3 at 11q23.1-q23.2 delineated by
      markers D11S1347 and D11S4142 and spanning approximately 5 Mb and a second 3-Mb
      region around marker D11S925 at 11q23.3 delineated by markers D11S528 and
      D11S1345. Both regions have been described as deletion targets or as being
      included within larger allelic deletions detected in several other common tumor
      types. Thus, these 2 putative melanoma-suppressor loci are likely to harbor tumor
      suppressor genes relevant to tumorigenesis of melanoma and a number of other
      common human malignancies.

PMID- 9935202
TI  - Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps.
AB  - Altered mucin glycosylation and the de novo appearance of gastric mucin antigens
      have been described in colonic adenomas. The purpose of our study was to
      determine if expression of the gastric mucin genes MUC5AC and MUC6 occurs in
      colorectal adenomas and whether this correlates with histopathologic criteria of
      malignant potential. Immunohistochemical staining using antibodies against MUC5AC
      and MUC6 tandem repeat synthetic peptides was performed on specimens of normal
      colon mucosa (n = 26), hyperplastic polyps (n = 9) and adenomatous polyps (n =
      111). Mucin mRNA levels were determined using RNase protection assays using
      riboprobes corresponding to unique non-repetitive sequences. MUC5AC and MUC6
      staining were rarely detected and of low intensity in normal colon and
      hyperplastic polyps. The number of immunoreactive polyps and intensity of MUC5AC
      and MUC6 staining were greatest in larger adenomas of moderate villous histology
      and dysplasia. MUC5AC and MUC6 staining tended to decrease in highly villous
      polyps with severe dysplasia. Increased MUC5AC mRNA levels were found in 26/45 of
      adenomas tested compared with 0/9 normal colon specimens. MUC6 mRNA levels were
      found in 20/45 of adenomas compared with 1/9 normal colon specimens. MUC5AC and
      MUC6 mRNA were present more frequently and at higher levels in polyps with
      intermediate stages of size, villous histology and dysplasia. We conclude that
      aberrant expression of MUC5AC and MUC6 mucin genes is likely responsible for an
      expanded repertoire of mucin antigen expression in colorectal neoplasia.

PMID- 9935204
TI  - The role of reproductive factors and use of oral contraceptives in the aetiology
      of breast cancer in women aged 50 to 74 years.
AB  - It is unclear whether age at menarche is causally involved in breast-cancer
      aetiology, or serves a correlate of other early-life exposures. Other aspects of
      reproductive life, including cycle length and regularity, climacteric symptoms,
      reproductive history and oral contraceptive use, are also incompletely
      investigated. We examined these issues in a population-based case-control study,
      including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263
      controls of similar age. Mailed questionnaires and telephone interviews were used
      to collect information on menstrual and reproductive characteristics as well as
      use of oral contraceptives. We found a statistically significant negative
      association between increasing age at menarche and breast-cancer risk in women
      born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to
      be adversely related to breast-cancer risk, with OR for women with cycle lengths
      < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle
      length of 28 days. There was a strong trend of decreasing breast-cancer risk with
      increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation,
      menopausal symptoms or past use of oral contraceptives did not appear associated
      with breast-cancer risk. Our findings provide some evidence of a role of
      environmental correlates of early menarche in breast-cancer aetiology, and
      underline the importance of childbirth, especially early in life, in the
      prevention of breast cancer. Our data are not readily compatible with an
      important influence of former oral contraceptive use on post-menopausal breast
      cancer risk.

PMID- 9935203
TI  - Tumor regressions observed in patients with metastatic melanoma treated with an
      antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.
AB  - Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3
      subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No
      significant toxicity was observed. Of the 25 patients who received the complete
      treatment, 7 displayed significant tumor regressions. All but one of these
      regressions involved cutaneous metastases. Three regressions were complete and 2
      of these led to a disease-free state, which persisted for more than 2 years after
      the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL)
      response was found in the blood of the 4 patients who were analyzed, including 2
      who displayed complete tumor regression. Our results suggest that injection of
      the MAGE-3.A1 peptide induced tumor regression in a significant number of the
      patients, even though no massive CTL response was produced.

PMID- 9935206
TI  - Biologically relevant phenotypic changes and enhanced growth properties induced
      in B lymphocytes by an EBV strain derived from a histologically aggressive
      Hodgkin's disease.
AB  - Epstein-Barr virus (EBV) isolates show a wide genomic heterogeneity, and a key
      issue is whether distinct strain variations may contribute to the development
      and/or malignancy of EBV-related disorders. Herein, we report on the virologic
      and biologic characterization of an EBV strain derived from a cyto-histologically
      aggressive EBV-related Hodgkin's disease (HD) (case HD-3) showing a high number
      of "anaplastic" Reed-Sternberg cells expressing markedly high levels of CD30,
      CD40 and LMP-1. The HD-3-derived EBV showed strong in vitro immortalizing
      properties, as suggested by the unusually high number of spontaneous
      lymphoblastoid cell lines (LCLs) obtained from the patient. Immunofluorescence
      and immuno-cytochemical analyses showed that HD-3 LCLs expressed significantly
      higher levels of CD23, CD30, CD38, CD39, CD40 and CD71 antigens and CD54 and CD58
      adhesion molecules than B95.8 LCLs. In contrast, the expression of CD11a, CD24,
      CD95, bcl-2, LMP-1 and EBNA-2 was similar in both groups of LCLs. These
      phenotypic changes are consistent with the induction of a pronounced activation
      status and are not dependent on the cellular background, having been closely
      reproduced by the same virus in LCLs from an unrelated donor (DEN-HD-3 LCLs). HD
      3 LCLs were able to grow in vitro at low serum concentrations (up to 0.1%) and
      were significantly more clonogenic in soft agarose than B95.8 LCLs. Moreover,
      although no evidence of tumor formation was observed in nude mice injected with
      B95.8 LCLs, all 5 spontaneous LCLs of patient HD-3 and the 2 DEN-HD-3 LCLs grew
      in transplanted animals as lymphoproliferations composed of EBER+, LMP-1+ cells.
      Our findings indicate that the biologic properties of the HD-3 EBV strain are
      significantly different from those of the B95.8 virus and may have contributed to
      the cytologic and histo-pathologic malignancy of this HD case. Moreover,
      molecular characterization of the HD-3 EBV genome identified a 63-bp deletion
      within the 3' end of the LMP-1 gene as a likely significant change that may be
      responsible, at least in part, for the biologically relevant phenotypic
      modifications and enhanced in vitro and in vivo growth potential induced in B
      lymphocytes by this virus strain.

PMID- 9935205
TI  - Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) has been suggested to play an etiological role in the
      development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another
      study in Scotland questioned increased risk of development of NHL in patients
      with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in
      Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during
      the period from 1957 to 1997 were followed up from the date of diagnosis of
      chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person
      years of observation were accrued with a follow-up period ranging from 0.25 to
      40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The
      interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13)
      years. Expected number of cases of NHL in the sex-, age- and calendar year
      matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95%
      confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for
      hepatocellular carcinoma among patients with HCV infection into account, chronic
      HCV infection was considered to be moderately associated with increased risk of
      NHL.

PMID- 9935207
TI  - Expression of bone morphogenetic protein 6 in normal mammary tissue and breast
      cancer cell lines and its regulation by epidermal growth factor.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional regulators of
      proliferation, differentiation and apoptosis. BMP-6 is involved in numerous
      developmental processes. We have demonstrated expression of BMP-6 in breast
      cancer cell lines by RT-PCR and immuno-histochemistry. The level of BMP-6 mRNA
      decreased upon serum starvation, whereas epidermal growth factor (EGF) treatment
      led to elevation of BMP-6 mRNA levels in a dose-dependent manner, with a maximum
      at 50 ng/ml EGF under serum-free conditions in hormone-sensitive (MCF-7) and in
      hormone-insensitive (SK-BR-3) breast cancer cell lines. The EGF-like growth
      factors transforming growth factor-alpha, amphiregulin and betacellulin were also
      able to elevate the BMP-6 mRNA level after 24 hr. Inhibition of EGF receptor
      tyrosine kinase with tyrphostine AG 1517 repressed the inductive effect of these
      growth factors, indicating an EGF receptor-mediated regulation of BMP-6 mRNA. In
      addition, BMP-6 mRNA was detected in tumor samples from breast carcinoma
      patients. However, levels were reduced in 18/44 samples compared with tumor-free
      resection margins. In 12 of these 18 patients, at least a 10-fold reduction of
      EGF receptor mRNA levels in tumor samples vs. tumor-free samples was observed.
      This suggests a putative relationship between EGF receptor and BMP-6 mRNA levels
      in breast cancer.

PMID- 9935208
TI  - Over-production of parathyroid hormone-related peptide results in increased
      osteolytic skeletal metastasis by prostate cancer cells in vivo.
AB  - Prostate carcinoma is one of the most common malignancies affecting males,
      resulting in a high rate of morbidity and mortality. This hormone-dependent
      malignancy is characteristically associated with a high incidence of osteoblastic
      skeletal lesions. However, osteolytic lesions invariably accompany blastic ones.
      In the current study, we assessed the role of parathyroid hormone-related peptide
      (PTHRP), a potent bone-resorbing agent, in contributing to bone breakdown and
      prostatic skeletal metastasis using a syngeneic rat prostate cancer model. The
      full-length cDNA encoding rat PTHRP was subcloned as a Hind III insert in the
      sense orientation into the mammalian expression vector pRc-CMV to generate the
      expression vector pRc-PTHRP-S. Both control and experimental plasmids were stably
      transfected into low PTHRP-producing Dunning R3227, Mat Ly Lu rat prostate cancer
      cells. Following antibiotic selection, monoclonal cell lines expressing the
      highest amount of PTHRP mRNA and immunoreactive PTHRP were selected as
      experimental tumor cells for further analysis. Increased PTHRP production by
      these cells had no significant effect in vitro on the invasive capacity of these
      cells. Control and experimental cells were inoculated s.c. into the right flank
      or by the intracardiac (i.c.) route into the left ventricle of inbred male
      Copenhagen rats. No skeletal metastases occurred after s.c. injection with either
      cells. In contrast, i.c. inoculation led to lumbar vertebra metastasis and
      consequent hind-limb paralysis. Furthermore, histological examination of skeletal
      metastases in experimental animals showed a marked increase in osteoclastic
      activity. Our results demonstrate that PTHRP can increase osteoclastic osteolysis
      in the presence of focal osseous prostate cancer metastases and may contribute to
      the lytic lesions which generally accompany osteoblastic lesions in prostate
      cancer.

PMID- 9935209
TI  - A new monoclonal antibody that specifically recognises the MDR-3-encoded gene
      product.
AB  - The MDR-3-encoded P-glycoprotein (Pgp) is highly expressed in liver and is
      thought to function as a hepatic transporter of phospholipids into bile. However
      its role, if any, in other tissues remains undefined. Although transfection
      experiments have indicated that it may be unable to confer drug resistance, there
      is evidence that it may be involved in drug resistance in certain B-cell
      leukaemias. To date, most work on clinical samples has been performed at the mRNA
      level; limited work has been performed using polyclonal antibodies raised to MDR
      3 and mdr-2 (the murine equivalent of MDR-3). We have generated a new monoclonal
      antibody, termed 6/1G, which specifically recognises the human MDR-3 gene-encoded
      product. Antibody 6/1G was produced by in vitro immunisation of spleen cells from
      BALB/c mice with a synthetic 12-amino acid peptide. Cells from MDR-3 transgenic
      mice showed consistent membranous staining with antibody 6/1G. Immunoblotting
      with 6/1G identified a band at 170 kDa on lysates of MDR-3 transgenic cells.
      Preliminary results with a range of B-cell leukaemias suggest that MDR-3 Pgp
      positivity may be a marker for a more malignant phenotype in B-CLL. Antibody 6/1G
      may be useful in defining a role for MDR-3 in malignancy and drug resistance, as
      well as in certain liver diseases such as progressive familial intracholeostasis.

PMID- 9935210
TI  - A selective retinoid with high activity against an androgen-resistant prostate
      cancer cell type.
AB  - Retinoic acid (RA) and its natural and synthetic analogs, the retinoids, regulate
      many biological processes, including development, differentiation, cell growth,
      morphogenesis, metabolism and homeostasis. Retinoid effects are mediated by
      specific nuclear receptors, the RARs and RXRs. Because of their ability to
      control cell growth and induce differentiation, retinoids are being examined for
      the prevention and treatment of several cancers. The majority of retinoids so far
      analyzed and available inhibit primarily cell proliferation and tumor progression
      but cannot eliminate cancer cells. In addition, the beneficial effects of the
      natural retinoids are undermined by undesirable side effects, possibly due to
      indiscriminate activation of all retinoid receptor subtypes and response
      pathways. Here, we show that a synthetic retinoid, CD-271, that activates
      selectively the RAR gamma subtype in a given context, shows increased anti
      proliferative activity against certain carcinoma cells over all-trans-retinoic
      acid (tRA). CD-271 exhibits enhanced activity against DU-145 prostate
      adenocarcinoma cells through apoptosis-inducing activity, while tRA does not. The
      selective anti-cancer cell action appears to be receptor-mediated as an RAR
      antagonist reverses the inhibition. This profile was not seen with other
      selective retinoids, such as RAR alpha-selective agonists, anti-AP-1 compounds
      and a non-apoptosis inducing RAR gamma agonist. Our data point to a specific role
      for RAR gamma in controlling the growth of the prostate, consistent with previous
      RAR gamma gene knockout data. The identified retinoid represents a new class of
      compounds with potential for the treatment of prostate cancer.

PMID- 9935211
TI  - Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to
      cisplatin in human head-and-neck carcinoma cells.
AB  - Tunicamycin (TM), a naturally occurring antibiotic, blocks the first step in the
      biosynthesis of N-linked oligosaccharides in cells. In this study, we
      investigated whether changes in N-linked glycosylation affect the sensitivity of
      head-and-neck carcinoma cell lines to cis-diaminedichloroplatinum(II) (cisplatin)
      in vitro and in vivo. In vitro treatment of the IMC-3 and KB cell lines with TM
      significantly decreased the 50% inhibitory concentration (IC50) of cisplatin, as
      determined by the MTT assay (24.15 to 10.97 microg/ml, p < 0.05). In addition, TM
      significantly decreased the IC50 of cisplatin against established cisplatin
      resistant IMC-3/CR cells (>100 to 14.4 microg/ml, p < 0.05) to levels similar to
      those against parental IMC-3 cells. TM treatment decreased the number of Con A-
      and L-PHA-binding sites on the surface of tumor cells but had no effect on the
      intracellular platinum concentration. Induction of apoptosis in vitro by TM plus
      cisplatin in combination was increased compared with that by cisplatin alone.
      Furthermore, in vivo administration of TM plus cisplatin in combination
      significantly inhibited local tumor growth in the cisplatin-resistant in vivo
      C3H/He mouse model as compared with the control group (p < 0.05) and increased in
      vivo apoptosis of tumor cells. Our results suggest that the manipulation of
      glycosylation by TM in tumor cells might be a useful therapeutic strategy for
      successful chemotherapy using cisplatin against head-and-neck cancer.

PMID- 9935212
TI  - Migration properties of the human ovarian adenocarcinoma cell line IGROV1:
      importance of alpha(v)beta3 integrins and vitronectin.
AB  - Cell migration of ovarian tumoral cells is essential for cell dissemination and
      for invasion of the submesothelial extracellular matrix (ECM). We have conducted
      a study of the migratory properties of an ovarian adenocarcinoma cell line
      (IGROV1) by using 2 distinct methods for the evaluation of cell migration. We
      found that in a short-term transfilter migration assay, IGROV1 cells migrated
      toward vitronectin, fibronectin, type IV collagen and laminin in an integrin
      dependent manner. When migration was evaluated in a wound healing assay, the
      restitution of the wounded area was stimulated solely by added, exogenous
      vitronectin and was almost totally dependent on alpha(v)beta3 integrin function.
      Moreover, we demonstrated that alpha(v)beta3 was localized in focal contacts
      restricted to the leading edge of migrating cells, whereas vitronectin notably
      localized with actin stress fibers and cortical actin. On the other hand, several
      kinase inhibitors were found to impede migration of IGROV1 induced by
      vitronectin. It thus appears that alpha(v)beta3-vitronectin interactions lead to
      the activation of multiple signaling pathway including activation of protein
      kinase C, phosphatidyl-inositol-3-phosphate kinase and protein tyrosine kinase.
      The "alpha(v)beta3-vitronectin system" is therefore essential to the migration of
      human ovarian carcinoma cells.

PMID- 9935213
TI  - Modification of blood flow in the HSN tumour and normal tissues of the rat by the
      endothelin ET(B) receptor agonist, IRL 1620.
AB  - Activation of endothelin receptors on the vasculature can produce a variety of
      responses from potent vasoconstriction to mild vasodilation, depending on the
      receptor complement within the tissue. To elucidate the potential role of
      endothelin analogues as tumour blood flow modifiers, we have evaluated the effect
      of the ET(B) receptor agonist, IRL 1620 ([Suc-(Glu9, Ala(11,15))-ET-1(8-21)]) in
      CBH/CBi rats bearing an HSN fibrosarcoma. Tissue blood flow and vascular
      resistance were determined, 20 min following administration of IRL 1620 (bolus
      intravenous), using the uptake of radiolabelled iodoantipyrine (125I-IAP). Blood
      flow was unchanged in most tissues. However, at doses > or = 1.0 nmol kg(-1) IRL
      1620, blood flow in the brain and heart was increased, whereas in the small
      intestine it was reduced. Blood flow in the skeletal muscle was reduced at 1.0
      nmol kg(-1) only. Tumour blood flow was significantly reduced at 3.0 and 5.0 nmol
      kg(-1). Vascular resistance was unchanged in most tissues although it was
      increased in the skeletal muscle at 1.0 nmol kg(-1), in the kidney at 1.0 and 3.0
      nmol kg(-1) and in the brain and heart, it was reduced at 5.0 nmol kg(-1) IRL
      1620. Vascular resistance was significantly increased in the tumour and the small
      intestine at doses > or = 1 nmol kg(-1) IRL 1620. Pretreatment of rats with BQ
      788, an ET(B) receptor antagonist, selectively attenuated the tumour vascular
      response to 3 nmol kg(-1) IRL 1620 with no changes observed in the normal tissue
      responses. Our results demonstrate that the HSN tumour vasculature is selectively
      responsive to IRL 1620 at doses > 1 nmol kg(-1) compared with the majority of
      normal tissues with the exception of the small intestine, and that only the
      tumour response is highly sensitive to BQ-788 antagonism, under the experimental
      dosing regime investigated. These differences may be exploitable for therapeutic
      benefit.

PMID- 9935214
TI  - Mesothelial cells induce the motility of human ovarian carcinoma cells.
AB  - The dissemination of ovarian carcinoma cells within the abdominal cavity involves
      interaction of tumor cells with the peritoneal mesothelium. The aim of our study
      was to investigate whether mesothelial cells might directly affect the spreading
      of this tumor by inducing motility and invasiveness of human ovarian carcinoma
      cells. Serum-free supernatants of cultured human mesothelial cells [conditioned
      medium (CM)] induced chemotaxis and invasiveness of the human ovarian carcinoma
      cell lines SK-OV-3, OVCAR-5 and A2780 in a Boyden chamber. Checkerboard analysis
      indicated that the stimulated motility was prevalently directional. Most of the
      chemotactic activity was retained by a heparin affinity column, indicating that
      the motility factor(s) is a heparin-binding protein. Using different monoclonal
      antibodies (MAbs) directed against chemotactic factors that are secreted by
      mesothelial cells, we found that chemotaxis was partially prevented (64.8%
      inhibition) by antibodies against fibronectin (FN). CM also induced haptotactic
      migration of ovarian carcinoma cells, and anti-FN antibodies significantly
      inhibited haptotaxis. The presence of FN in the CM was confirmed by Western blot
      analysis. Our findings suggest that mesothelium plays an active role in inducing
      the intraperitoneal spread of ovarian carcinoma cells, and point to FN as being
      one of the main mediators of mesothelium-induced ovarian carcinoma cell motility.

PMID- 9935215
TI  - Tumor-specific cytokine release by donor T cells induces an effective host anti
      tumor response through recruitment of host naive antigen presenting cells.
AB  - We recently reported that tumor eradication induced by immunotherapy (IT) in a
      congenic mouse model using tumor infiltrating lymphocytes (TIL) + recombinant
      interleukin-2 (rIL-2) is dependent on recruitment of naive host immune cells at
      the tumor sites. The recruitment of host immune cells was induced mainly through
      a local secretion of interferon-gamma (IFN-gamma) produced by donor T cells. We
      now further investigated how a non-specific inflammatory response progresses to a
      host T-cell-mediated tumor-specific response. In cross-over experiments using MCA
      105 and MCA-205 sarcoma tumors, pulmonary metastatic disease was eradicated only
      in mice treated with tumor-matched TIL + rIL-2. In vitro, TIL stimulated with the
      tumor of origin secreted relatively high levels of IFN-gamma and granulocyte
      macrophage colony stimulating factor (GM-CSF) compared to TIL stimulated with
      mismatched tumor cells. In lungs of tumor-bearing mice treated with matched TIL +
      rIL-2, significant increases in the percentages of IFN-gamma, GM-CSF and tumor
      necrosis factor-alpha (TNF-alpha) positive cells were detected, as well as of
      macrophages, natural killer (NK) cells and dendritic cells. Depletion of
      macrophages or NK cells did not inhibit the efficacy. In contrast, depletion of
      dendritic cells partially inhibited the efficacy of the treatment. Combined
      depletion of dendritic cells and macrophages abrogated more than 80% of the
      efficacy. Our data suggest that successful IT may require 3 steps: (1) release of
      inflammatory cytokines by donor TIL after restimulation by tumor cells; (2)
      infiltration of host immune cells in response to local cytokine production; and
      (3) activation of tumor-specific host immune cells by dendritic cells and to a
      lesser extent by macrophages.

PMID- 9935216
TI  - Angiogenesis inhibitors overcome tumor induced endothelial cell anergy.
AB  - We report here that tumor angiogenesis-mediated endothelial cell (EC) anergy can
      be overcome by inhibitors of angiogenesis. We found previously that tumor growth,
      known to be dependent on angiogenesis, results in down-regulation of endothelial
      adhesion molecules and tumor EC anergy to inflammatory signals. We hypothesized
      that counteracting angiogenesis induces re-expression of adhesion molecules and
      normalizes responses to inflammatory cytokines. Here, we present data to show
      that the angiogenesis inhibitor platelet factor-4 (PF4) is able to prevent basic
      fibroblast growth factor (bFGF)-induced down-regulation of intercellular adhesion
      molecule-1 (ICAM-1). Furthermore, PF4 restores ICAM-1 expression following bFGF
      induced down-regulation of ICAM-1. This PF4 effect occurs at the protein level
      and the RNA level and it has functional impact on leukocyte adhesion. In
      addition, PF4 overcomes the tumor-induced EC anergy to inflammatory signals such
      as tumor necrosis factor alpha (TNF alpha). Our findings may be the basis of new
      cancer therapies by combining anti-angiogenic therapy and immunotherapy to
      decrease blood vessel formation and to increase the effectiveness of inflammatory
      reactions against tumors.

PMID- 9935217
TI  - Efficient adenoviral transfer of NF-kappaB inhibitor sensitizes melanoma to tumor
      necrosis factor-mediated apoptosis.
AB  - It has been suggested that the in vitro cytotoxicity of tumor necrosis factor
      (TNF) toward a number of transformed cell lines could make it a useful agent for
      anti-tumor therapy. However, many tumor cell lines are resistant to TNF-induced
      cell death. It has been shown that transcription factors of the NF-kappaB family,
      which are themselves activated by TNF, could protect cells against apoptotic cell
      death. To test whether melanoma cells, which are normally resistant to TNF
      mediated killing, can be made susceptible by inhibiting the activation of NF
      kappaB, we generated a recombinant adenovirus expressing a dominant mutant form
      of IkappaB alpha under the control of a CMV promoter. We show here that
      adenovirus-mediated inhibition of NF-kappaB function rendered melanoma cells
      susceptible to the cytotoxic effects of TNF, and thus that NF-kappaB-inhibiting
      adenoviruses could become useful adjuvants in TNF-based anti-tumor therapies.

PMID- 9935218
TI  - Improved efficacy of dendritic cell vaccines and successful immunization with
      tumor antigen peptide-pulsed peripheral blood mononuclear cells by
      coadministration of recombinant murine interleukin-12.
AB  - The well-characterized P815 tumor model was used to optimize anti-tumor
      immunization approaches in mice. Tumor peptides derived from antigens P198 or P1A
      were targeted to antigen-presenting cells (APC) by ex vivo pulsing. Initial
      experiments with irradiated pulsed splenic dendritic cells (sDC) injected weekly
      in the hind footpads for 3 weeks demonstrated cytolytic T lymphocyte (CTL)
      generation in 10-20% of mice. Because of the importance of interleukin-12 (IL-12)
      in tumor rejection responses, pulsed sDCs also were given together with
      recombinant murine IL-12 (rmIL-12). This strategy induced peptide-specific CTL in
      100% of the mice. The IL-12 had to be injected in the footpads on days 0, 1 and 2
      of each immunization week to achieve an optimal effect. The improvement seen with
      the addition of IL-12 prompted examination of other sources of APC. Purified
      resting B cells, lipopolysaccharide (LPS) blasts and nonfractionated splenocytes
      or peripheral blood mononuclear cells (PBMC) were pulsed with peptide and
      administered with the same schedule of rmIL-12. Because these cell types appeared
      to bind peptides less avidly than did DC, increasing peptide doses were used
      during pulsing. Interestingly, immunization with each of these APC also induced
      specific CTL in 100% of mice, provided rmIL-12 was coadministered. CTLs were
      detected both in the spleen and in the peripheral blood. Immunization with
      irradiated, P1A-pulsed PBMC plus rmIL-12 resulted in protection against challenge
      with tumors expressing the specific antigen in all mice. The ease by which human
      patient PBMCs can be prepared provides a straightforward vaccination approach to
      be used in clinical trials of peptide-based immunization in melanoma.

PMID- 9935219
TI  - Human papillomavirus-5b DNA integrated in a metastatic tumor: cloning, nucleotide
      sequence and genomic organization.

PMID- 9935220
TI  - Telomerase components as a diagnostic tool in human oral lesions.
AB  - Telomerase activity is considered to be a diagnostic marker of malignancy since
      most malignant cells express this activity and most somatic cells do not.
      However, the detection of telomerase activity is rather complicated and is
      affected by many factors. Recently, human telomerase components were cloned and
      found to consist of 3 subunits. We assessed which component of telomerase best
      correlates with malignancy in order to study the possibilities for developing a
      new diagnostic marker. Telomerase activity was measured by a telomeric repeat
      amplification protocol (TRAP) assay, and the telomerase components hTR, hTRT-mRNA
      and TP1-mRNA were detected by the reverse transcriptase-polymerase chain reaction
      (RT-PCR). Twenty-five of 26 oral malignant lesions, 9 of 22 benign lesions and
      none of 19 normal control tissues exhibited distinct telomerase activity. hTR and
      TP1-mRNA expression levels were detected in all malignant lesions and normal
      control tissues and had no significant correlation with the telomerase activity
      results. In contrast, hTRT-mRNA expression was closely associated with telomerase
      activity. All lesions expressing hTRT were telomerase positive. In addition, some
      samples of dysplastic lesions, benign tumors, lichen planus and normal mucosa
      exhibiting poor telomerase activity revealed weak expression of hTRT. Expression
      levels of hTRT-mRNA positively correlated with clinical and pathological
      findings. Detection of hTRT-mRNA by RT-PCR appeared to be more sensitive for
      telomerase than measurement of telomerase activity by the TRAP assay. Detection
      of hTRT-mRNA may provide information useful in the diagnosis of oral
      malignancies.

PMID- 9935221
TI  - Hyperthermia for treatment of rectal cancer: evaluation for induction of
      multidrug resistance gene (mdr1) expression.
AB  - Environmental stress factors, such as heat, may induce multidrug resistance gene
      (mdr1) expression, which could result in the disadvantageous multidrug resistance
      (MDR) phenotype. To evaluate this possibility in a clinical situation, we
      investigated mdr1 gene expression in patients with locally advanced rectal cancer
      who underwent preoperative radio-chemo-thermo-therapy (RCTT). Patients were
      classified into groups according to the treatment schedule of RCTT vs. radio
      chemo-therapy (RCT) without hyperthermia (control group). Expression of the mdr1
      gene was analyzed in tumors and normal rectal tissues prior to and post-treatment
      (RCTT or RCT, respectively) by means of semi-quantitative and quantitative
      reverse transcription-polymerase chain reaction (RT-PCR). The data were
      correlated with therapeutic response and survival parameters. Based on our
      evaluation criteria, in 2 of 19 tumors of the RCTT group, mdr1 gene expression
      was increased more than 2-fold; in 3 of 19 tumors of this group, however, mdr1
      expression was decreased more than 2-fold. In the patient control group, levels
      of mdr1 gene expression were reduced in 2 of 8 tumors. Thus, hyperthermia
      combined with RCT (RCTT) in comparison with RCT alone does not lead to an
      increase in mdr1 gene expression in patients with locally advanced rectal cancer
      within the preoperative treatment schedule. The risk of inducing the classical
      multidrug resistance phenotype by hyperthermia was thus minimal in this clinical
      setting. Subsequent adjuvant chemotherapy should thus not be hindered.

PMID- 9935222
TI  - N-acetyl transferase 2 genotypes, meat intake and breast cancer risk.
AB  - Heterocyclic amines (HAs) are carcinogens produced by high-temperature cooking of
      meat and animal protein; metabolism of HA is influenced by polymorphisms in the N
      acetyltransferase-2 (NAT-2) gene. Data from a variety of sources suggest that HA
      may play a role in human carcinogenesis. We examined the associations between
      meat intake and cooking method, acetylator genotype and breast cancer risk in a
      sub-cohort of 32,826 women in the Nurses' Health Study who gave a blood sample in
      1989-1990. Women who were diagnosed with breast cancer (n = 466) after blood draw
      and prior to June 1, 1994, were matched to 466 controls. Overall, rapid
      acetylators were not at increased risk of breast cancer compared with slow
      acetylators (multivariate OR = 1.1, 95% CI 0.8-1.5), and there were no
      associations between meat intake or cooking method of meat and breast cancer
      risk. Rapid acetylators with the highest red meat intake (one or more servings
      per day) were not at increased risk of breast cancer compared with slow
      acetylators with the lowest red meat intake (OR = 1.1, 95% CI 0.7-1.8). Frequent
      intake of charred meat among rapid acetylators (one or more times per week) was
      not associated with increased risk (OR = 1.2, 95% CI 0.6-2.3) compared with slow
      acetylators who ate charred meat less than once per month. We observed no
      significant associations for rapid acetylators who frequently consumed beef, pork
      or lamb cooked with high-temperature cooking methods, such as barbecuing (OR =
      0.9, 95% CI 0.4-1.9) or roasting (OR = 0.9, 95% CI 0.5-1.6). Our data suggest
      that HAs may not be a major cause of breast cancer, although we cannot exclude
      misclassification of HA intake as the reason for the lack of association. We
      observed no evidence of differential susceptibility to these exposures by NAT2
      genotype.

PMID- 9935223
TI  - New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism
      among lung-adenocarcinoma patients in Japanese.
AB  - MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the
      mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in
      human MMH/OGG1 gene were newly identified and analyzed to examine a possible
      association with lung-cancer risk by a population-based study. Polymorphic allele
      3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with
      adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI):
      1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a
      role in predisposition to lung cancer.

PMID- 9935224
TI  - Microsatellite analysis reveals deletion of a large region at chromosome 8p in
      conventional renal cell carcinoma.
AB  - Loss of heterozygosity (LOH) at chromosome 8p is associated with the progression
      of conventional (non-papillary) renal cell carcinomas (RCC). To determine the
      tumor suppressor gene locus, we carried out a deletion mapping of chromosome 8p
      at 10 microsatellite loci in 96 RCCs. LOH occurred in 32% of the tumors. The
      smallest overlapping region of deletion at chromosome 8p11.2-p23.1 corresponds to
      approximately 34-cM genetic distance. No small interstitial deletion was seen.

PMID- 9935225
TI  - Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral
      cancer.
AB  - Frequent loss of heterozygosity on chromosome 8p in a variety of human
      malignancies, including head and neck cancers, has suggested the presence of a
      tumor suppressor gene (or genes) associated with the pathogenesis of these
      cancers. To test the role of genetic alterations at 8p23 in oral carcinogenesis,
      we studied 51 squamous cell carcinomas of the head and neck and 29 oral squamous
      cell carcinoma cell lines for allelic loss using 7 microsatellite markers
      spanning approximately 5 cM of chromosome band 8p23. Twenty-three of 51 tumors
      (45%) and 23 of 29 cell lines (79%) showed allelic loss at 1 or more loci. Three
      cell lines showed homozygous deletion of loci within a 3 cM region defined by the
      markers D8S1781 and D8S262. Our results suggest that a tumor suppressor gene (or
      genes) is located in 8p23 and is associated with the development and/or
      progression of oral carcinomas.

PMID- 9935226
TI  - Distinct frequency of ret rearrangements in papillary thyroid carcinomas of
      children and adults from Belarus.
AB  - Rearrangements of the ret oncogene were investigated in papillary thyroid
      carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the
      time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed
      Belarussian adults and 16 PTC from German patients without radiation history were
      included in the study. ret rearrangements were detected and specified by RT-PCR
      and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only
      ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of
      69% for the Belarussian cases, but of only 19% in the German patients. In
      contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present
      in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of
      ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases
      and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1)
      similar to that in earlier investigations (diagnosed 1991-94) was obtained for
      cases included in our study that were diagnosed in 1993/94. The present data
      suggest that ret/PTC3 may be typical for radiation-associated childhood PTC with
      a short latency period, whereas ret/PTC1 may be a marker for later-occurring PTC
      of radiation-exposed adults and children.

PMID- 9935227
TI  - Induction of tyrosinase-reactive T cells by treatment with dacarbazine,
      cisplatin, interferon-alpha +/- interleukin-2 in patients with metastatic
      melanoma.
AB  - We have shown the presence of tyrosinase-reactive T cells in the peripheral blood
      of melanoma patients, who had been in remission after treatment with IL-2
      containing regimens. In this consecutive study, we analyzed the T-cell response
      to various peptides derived from tyrosinase in serial blood samples obtained from
      7 stage-IV melanoma patients before, during and following treatment. All patients
      were treated within a randomized trial (EORTC 18951) with cisplatin (CDDP),
      dacarbazine (DTIC), interferon-alpha (IFN-alpha) +/- interleukin-2 (IL-2). Using
      an ELISPOT assay detecting peptide-specific IFN-gamma release, we measured the T
      cell response to 4 different HLA class I-binding peptide epitopes derived from
      tyrosinase containing an HLA-A2.1-, HLA-A24- or HLA-B44-binding motif in
      peripheral-blood mononuclear cells (PBMC). In one patient, tyrosinase-reactive T
      cells were detected before therapy. In 4 out of 7 patients, tyrosinase-reactive T
      cells against both HLA-A2.1-binding peptides and the B44-binding peptide became
      detectable at frequencies of up to 30 in 5 x 10(5) lymphocytes following
      treatment. These patients received CDDP, DTIC and IFN-alpha, 2 of them without IL
      2 and 2 with IL-2, resulting in one complete remission and 3 partial remissions.
      Two patients relapsed 8 and 9 months after treatment. At the time of relapse, no
      T cells reactive with tyrosinase were detectable. Our results show that high
      frequencies of tyrosinase-reactive T cells in the peripheral blood of melanoma
      patients can be induced by chemotherapy in combination with IFN-alpha, regardless
      of concomitant IL-2 administration.

PMID- 9935228
TI  - Tobacco, occupation and non-transitional-cell carcinoma of the bladder: an
      international case-control study.
AB  - Transitional-cell carcinoma is the dominant histological type of malignant tumors
      of the urinary bladder. There is limited information on risk factors for non
      transitional-cell carcinoma (NTCC) of the bladder. We used data from 9 case
      control studies on bladder cancer from 6 European countries to examine the
      association between NTCC, tobacco smoking and occupation. Information on 146
      cases diagnosed with NTCC were matched by age, gender and study center to 727 non
      cancer population or hospital controls and also with 722 transitional-cell
      bladder-cancer controls. Lifetime smoking and occupational history were
      evaluated. A statistically significant excess risk for NTCC was observed for
      current smoking [odds ratio (OR) = 3.61, 95% confidence interval (CI) 2.08-6.28].
      The risk increased with higher tobacco consumption (OR for highest tertile of
      pack-years = 7.01, 95% CI 3.60-13.66). The risks were higher for squamous-cell
      carcinomas than for other types of NTCC. Among major occupational groups, a
      significant excess risk was seen for field-crop and vegetable-farm workers (OR =
      2.06, 95% CI 1.03-4.10). These results indicate that NTCC of the bladder is
      associated with smoking and specific occupations. The risk pattern seems to
      differ, in part, from that observed for transitional-cell carcinoma of the
      bladder.

PMID- 9935229
TI  - Anti-proliferative activity of protein kinase C in apical compartments of human
      colonic crypts: evidence for a less activated protein kinase C in small adenomas.
AB  - The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal
      transduction in colorectal-cell lines. Its function in human colonic mucosal
      proliferation is controversial. Our study investigated the role of PKC with
      regard to proliferation and changes of PKC iso-enzyme expression in colonic
      biopsies compared with small adenomas. In short-term tissue-culture experiments
      of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical
      compartments of longitudinally sectioned crypts when PKC was activated by 200 nM
      of the phorbol ester TPA (n = 8). Thus, PKC inhibited growth of differentiated
      colonocytes which may influence cell homeostasis in colonic crypts. Furthermore,
      we have determined the expression of PKC alpha, -beta1, -beta2, -delta and 
      epsilon in colonic adenomas smaller than 1 cm in diameter of 18 patients and
      found a significant increase of PKC alpha in the cytosolic fraction and decreased
      membrane levels of PKC beta2 in adenomas compared to normal, neighboring mucosa
      while protein levels of PKC beta1, -delta and -epsilon were not altered. Moreover
      PKC delta but not PKC alpha mRNA expression was significantly lowered in adenoma
      tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes
      in the regulation patterns of PKC isoforms suggest a decreased activation state
      of PKC even in small adenomas. This is compatible with an anti-proliferative
      function of PKC serving to protect mucosa from expanding mutated cells.

PMID- 9935230
TI  - Disomy 1 with terminal 1p deletion is frequent in mass-screening-negative/late
      presenting neuroblastomas in young children, but not in mass-screening-positive
      neuroblastomas in infants.
AB  - The mass screening (MS) of neuroblastoma has been undertaken in Japan by
      measuring urinary catecholamine metabolites in infants at the age of 6 months. To
      clarify the biological characteristics of MS-positive (MS+) tumors in infants and
      MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic
      and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q
      probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas.
      The 246 tumors were classified into 4 groups on the basis of the constitution of
      chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors
      had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had
      trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells
      with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same
      copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion
      (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p
      groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p
      group (3/164) (p < 0.0001). Event-free survival at 5 years was lowest [19.5%; 95%
      confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the
      Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8)
      groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p
      group (p < 0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and
      55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were
      frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS
      program into reducing mortality from neuroblastoma.

PMID- 9935231
TI  - Human telomerase reverse transcriptase as a critical determinant of telomerase
      activity in normal and malignant endometrial tissues.
AB  - Telomerase activation is thought to be essential for cellular immortality and
      oncogenesis. It is observed in most malignant tumors but not in most normal
      somatic tissues. Normal human endometrium is, however, known to express
      significant telomerase activity in a menstrual phase-dependent manner. The 3
      major subunits composing telomerase have been identified. Using normal and
      malignant endometrial tissues, we studied how these components are involved in
      telomerase activation. A total of 23 endometrial cancers and 32 normal human
      endometria in various menstrual phases as well as cell lines derived from
      endometrial cancer were examined for the expression of each telomerase subunit
      using RT-PCR analysis. Telomerase activity in each sample was determined by the
      TRAP assay, and the correlation between subunit expression and telomerase
      activity was examined. RT-PCR analysis revealed that telomerase RNA (hTR) and
      telomerase-associated protein (TP1) mRNA were constitutively expressed in both
      normal and malignant endometrial tissues. Expression of human telomerase reverse
      transcriptase (hTERT) mRNA was observed in most endometrial cancers, while that
      in normal endometrium depended on the phases of menstrual cycles. Proliferative
      phase normal endometria expressed hTERT mRNA, while secretory phase endometria
      did not. There was a strong association between telomerase activity and hTERT
      expression but not TP1 or hTR expression in both normal and tumor tissues. Five
      telomerase-positive endometrial cancer cell lines expressed each of the
      telomerase subunits including hTERT, while 2 telomerase-negative normal primary
      fibroblast cells expressed TP1 mRNA and hTR, but not hTERT mRNA. Our findings
      suggest that hTERT is a rate-limiting determinant of enzymatic activity of human
      telomerase. Since some normal tissues with high regenerative potential can
      express hTERT, special attention should be paid to the clinical use of hTERT
      inhibitors as anti-cancer drugs.

PMID- 9935233
TI  - Presence of well-differentiated distal, but not poorly differentiated proximal,
      rat colon carcinomas is correlated with increased cell proliferation in and
      lengthening of colon crypts.
AB  - To determine whether colon crypt proliferative parameters were significantly
      altered by the stage of colon carcinogenesis or the type or location of colon
      tumors in rats, male Sprague-Dawley rats received an injection of the carcinogen
      1,2-dimethylhydrazine (12 mg DMH base/kg body weight) or DMH vehicle once a week
      for 8 weeks, then were killed 24 weeks later. Three hours before sacrifice, rats
      were injected with 1 mg/kg body weight colchicine to arrest mitotic cells at
      metaphase. Transverse sections of the colon mucosa were taken 6 cm from the anus
      and at least 3 cm from any tumor, fixed in formalin, then stained with
      hematoxylin & eosin (H&E) for analyses of proliferative parameters. Only
      complete, mid-axial crypts were scored for mitotic count (MC), crypt
      proliferative zone (PZ) height and crypt height (CH). Serial tumor sections were
      stained with H&E for histological evaluation or used in immunohistochemical
      detection of transforming growth factor alpha (TGF alpha). DMH treatment
      significantly increased MC, PZ and CH regardless of tumor status. The PZ and CH
      of rats with a carcinoma located in the distal colon were significantly increased
      compared with DMH-treated rats without an adenocarcinoma (AC) or with rats which
      had a tumor located in the proximal colon. Distal colon ACs were found to be well
      differentiated and to have greater TGF alpha immunoreactivity than the generally
      less differentiated proximal colon carcinomas. Distal colon AC production and
      systemic circulation of a soluble colon crypt stimulating factor such as TGF
      alpha may explain the significant increase in PZ and CH in histologically normal
      colonic mucosa located away from the tumor.

PMID- 9935232
TI  - Expression of the SART-1 tumor rejection antigen in breast cancer.
AB  - We investigated in breast cancers the expression of the SART-1 gene encoding
      tumor rejection antigens. SART-1 mRNA was expressed in all of the samples tested.
      The SART-1(800) antigen was detectable in 20 of 50 (40%) breast cancer tissues
      and all breast cancer cell lines tested, but not in normal breast tissues. The
      SART-1(800)+ breast cancer cells transfected with HLA-A2601 or HLA-A2402 cDNA
      were recognized by the HLA-A26-restricted and SART-1-specific cytotoxic T
      lymphocytes (CTLs) or the HLA-A24-restricted and SART-1-specific CTLs,
      respectively. Among the 20 SART-1(800)+ tumors, 9 or 8 tumors expressed estrogen
      receptor or progesterone receptor, respectively. Therefore, the patients with HLA
      A26 or -A24 haplotype might be appropriate candidates for specific immunotherapy
      with the SART-1 peptides independently or in combination with hormone therapy.

PMID- 9935234
TI  - Increased transforming growth factor-alpha levels in human colon carcinoma cell
      lines over-expressing protein kinase C.
AB  - Transforming growth factor-alpha (TGF-alpha) is synthesized as a membrane-bound
      precursor protein, pro-TGF-alpha, that is converted to a soluble form by 2
      endoproteolytic cleavages. Several factors have been implicated in the regulation
      of the second rate-limiting step, including protein kinase C (PKC). Earlier
      results indicated a potential role for the conventional class of PKC isozymes in
      the observed increase in TGF-alpha in the conditioned media of 2 human colon
      carcinoma cell lines. The present study addresses the potential role of specific
      PKC isozymes in this process using sense and anti-sense expression vectors for
      PKC isozymes. Two human colon carcinoma cell lines, HCT 116 and GEO, were
      transfected with plasmids, leading to the over-expression of PKC-alpha, -betaI or
      -betaII; and the secretion of TGF-alpha into the conditioned medium was
      determined. Over-expression of either PKC-betaI or PKC-betaII in these cell lines
      enhanced the levels of TGF-alpha in the media 2- to 5-fold. Over-expression of
      PKC-alpha did not alter the amount of TGF-alpha in the media to a significant
      extent. Transfection of HCT 116 cells with the anti-sense PKC-betaI cDNA resulted
      in a reduction in PKC-betaI protein expression. This was accompanied by a
      decrease in the amount of TGF-alpha in the conditioned media. Our results
      indicate that modulation of PKC-beta protein levels alters the amount of TGF
      alpha found in the conditioned media from these colon carcinoma cells.

PMID- 9935235
TI  - Granulocyte-colony-stimulating factor enhances invasive potential of human head
      and-neck-carcinoma cell lines.
AB  - Granulocyte-colony-stimulating factor (G-CSF), a hematopoietic cytokine,
      regulates the proliferation and differentiation of granulocytic progenitor cells
      and functionally activated mature neutrophils. G-CSF also affects
      nonhematopoietic tumor cells by the binding of G-CSF to its specific receptor (G
      CSFR) on the cells. In this study, we investigated the effect of G-CSF on the
      invasive potential of head-and-neck carcinoma cells, and explored the
      intracellular events initiated by the binding of G-CSF in tumor cells. In vitro
      treatment of head-and-neck-carcinoma cell lines, IMC-2, IMC-3, KB, Ca9-22, SCCKN
      and SCCTF, with recombinant G-CSF (rG-CSF) significantly augmented their invasive
      potential in dose- and time-dependent manners. Among these cancer cells, IMC-2,
      IMC-3, KB and Ca9-22 cells produced little G-CSF, while large amounts of G-CSF
      were produced by SCCKN and SCCTF cell lines. Anti-G-CSF antibody (Ab) abrogated
      the rG-CSF-enhanced invasiveness to the control level of that in untreated cancer
      cell lines. Immunocytochemical staining and Western blotting using anti-G-CSFR
      monoclonal antibody (MAb) revealed the expression of G-CSFR on head-and-neck
      cancer cell lines exhibiting the enhancement of invasive activity by rG-CSF. IMC
      2 cells, having the highest invasive ability among the cell lines used, showed
      augmentation of G-CSFR expression on stimulation with rG-CSF. Furthermore,
      stimulation of IMC-2 cells with rG-CSF induced rapid activation of tyrosine
      phosphorylated JAK1, suggesting that the G-CSF signal may be transduced into the
      cells through G-CSFR. Moreover, the gelatinolytic activity of IMC-2 cells was
      enhanced by stimulation of rG-CSF, and the enhanced invasiveness was inhibited on
      addition of the tissue inhibitors of metalloproteinases (TIMPs). These results
      suggest that exogenous rG-CSF may increase the risk of metastasis and/or local
      recurrence in patients with G-CSFR-positive head-and-neck squamous-cell
      carcinoma, via an invasive mechanism.

PMID- 9935236
TI  - Overexpression of transforming growth factor beta-type II receptor reduces
      tumorigenicity and metastastic potential of K-ras-transformed thyroid cells.
AB  - Expression of type II receptor of transforming growth factor beta (TbetaRII) is
      necessary for this factor to inhibit the growth of thyroid epithelial cells. In
      rat thyroid transformed cells, the resistance to transforming growth factor beta
      (TGFbeta) is associated with a decreased expression of TbetaRII mRNA and protein.
      Reduced TbetaRII expression has also been found in human thyroid differentiated
      and undifferentiated carcinomas. To investigate the role of TbetaRII in
      modulating the tumorigenic potential of k-ras-transformed thyroid cells, we
      transfected these cells with an expression vector carrying the human TbetaRII
      gene, regulated by an inducible promoter. Isolated clones, overexpressing
      TbetaRII, showed a reduction in the anchorage-dependent and -independent cell
      growth, compared with control k-ras-transformed cells. When transplanted in
      athymic nude mice, the transfected clones presented a decrease in tumorigenicity
      with respect to the highly malignant parental cells. Moreover, the diminished
      tumorigenic ability of the clones studied was accompanied by a statistically
      significant reduction in spontaneous and lung artificial metastases. Taken
      together, our data demonstrate that TbetaRII acts as a potent tumor suppressor
      gene when overexpressed in malignant thyroid cells.

PMID- 9935237
TI  - Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which
      induce tumor-reactive cytotoxic T lymphocyte.
AB  - Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a
      potential target for specific immunotherapy. HLA-A24 is the most frequent allele
      among Japanese and is also frequently present in Asians and Caucasians. We tested
      CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor
      cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T
      lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and
      autologous peptide-pulsed dendritic cells as antigen-presenting cells. This
      approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were
      capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA.
      The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it
      was inhibited by peptide-pulsed cold target cells as well as by anti-class I
      major histocompatibility complex (MHC) and anti-CD3 monoclonal antibodies (MAbs).
      The antigen specificity of the 2 CTL lines was examined using several tumor cell
      lines of various origins and for their peptide-dose responses. The identification
      of these novel CEA epitopes for CTL offers the opportunity to design and develop
      epitope-based immunotherapeutic approaches for treating HLA-A24+ patients with
      tumors that express CEA.

PMID- 9935238
TI  - Protein-kinase-Cmu expression correlates with enhanced keratinocyte proliferation
      in normal and neoplastic mouse epidermis and in cell culture.
AB  - In order to gain insight into the biological function of a PKC iso-enzyme, the
      protein kinase Cmu, we analyzed the expression pattern of this protein in mouse
      epidermis and keratinocytes in culture. Daily analysis of neonatal mouse
      epidermis immediately after birth showed a time-dependent reduction in the PKCmu
      content. Expression of the proliferating-cell nuclear antigen (PCNA), indicative
      of the proliferative state of cells, was reduced synchronously with PKCmu as the
      hyperplastic state of the neonatal tissue declined. In epidermal mouse
      keratinocytes, fractionated according to their maturation state, PKCmu expression
      was restricted to PCNA-positive basal-cell fractions. In primary cultures of
      those cells, growth arrest and induction of terminal differentiation by Ca2+
      resulted in strongly reduced PKCmu expression, concomitantly with the loss of
      PCNA expression. Treatment of PMK-R1 keratinocytes with 100 nM of the mitogen 12
      O-tetradecanoylphorbol-13-acetate (TPA) resulted in activation of PKCmu,
      reflected by translocation from the cytosolic to the particulate fraction and by
      shifts in electrophoretic mobility. DNA synthesis was significantly inhibited by
      the PKCmu inhibitor Goedecke 6976, while Goedecke 6983 did not inhibit PKCmu.
      Carcinomas generated according to the 2-stage carcinogenesis protocol in mouse
      skin consistently exhibited high levels of PKCmu. These data correlate PKCmu
      expression with the proliferative state of murine keratinocytes and point to a
      role of PKCmu in growth stimulation. A correlation between PKCmu expression and
      enhanced cell proliferation was also observed for NIH3T3 fibroblasts transfected
      with and overexpressing human PKCmu.

PMID- 9935239
TI  - Hyperthermic modulation of SN-38-induced topoisomerase I DNA cross-linking and SN
      38 cytotoxicity through altered topoisomerase I activity.
AB  - The effect of different temperatures (37-42.5 degrees C) on SN-38 (the active
      metabolite of CPT-11) cytotoxicity was examined in the human lung carcinoma cell
      lines H460 and Calu-6 as well as the murine fibrosarcoma cell line L929. The
      cytotoxicity of SN-38, determined by MTT cell survival assay, was significantly
      increased in each cell line in combination with 41.8 degrees C hyperthermia (x60
      120 min); the combination of SN-38 with 40.5 degrees C and 42.5 degrees C,
      however, was unchanged compared to 37 degrees C. Determination of topoisomerase
      (Topo) I DNA cross-linking in Calu-6 cells and L929 cells after treatment with SN
      38 showed the same temperature profile as seen in the cell-survival assays with
      increased Topo I DNA cross-linking after treatment with the combination of SN-38
      and 41.8 degrees C hyperthermia and unchanged Topo I DNA cross-linking at 40.5
      degrees C and 42.5 degrees C. To test the hypothesis that increased Topo I DNA
      cross-linking and SN-38 cytotoxicity at 41.8 degrees C is caused by hyperthermia
      modulated changes in Topo I activity, catalytic activity of Topo I extracted from
      each cell line and of purified human Topo I was determined at 20-42.5 degrees C.
      Topo I activity was found to be gradually increased with rising temperatures,
      resulting in significantly higher activity at 41.8 degrees C compared to 37
      degrees C; further increase of temperature past 41.8 degrees C decreased Topo I
      activity back to levels found at 37 degrees C. Our data are used to explain a
      series of events resulting in hyperthermic enhancement of Topo I DNA cross
      linking and SN-38 cytotoxicity in combination with 41.8 degrees C hyperthermia
      via increased Topo I activity.

PMID- 9935240
TI  - Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system
      using a recombinant Sindbis virus vector.
AB  - Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into
      tumor cells using virus-based vectors in conjunction with ganciclovir (GCV)
      exposure provides a potential gene therapy strategy for the treatment of cancer.
      The possibility of using a novel targetable Sindbis virus expression vector
      containing the HSV-TK gene was examined. Baby hamster kidney (BHK) cells and
      several human tumor cells infected with a Sindbis virus containing the HSV-TK
      gene showed strong expression of HSV-TK protein. Cells transduced with the HSV-TK
      gene exhibited increased TK activity, ranging from 3- to 20-fold over an average
      baseline level. The human HeLa-CD4+ cells infected with recombinant Sindbis virus
      containing the HSV-TK gene were sensitive to low concentrations of GCV (0.1-1
      microg/ml) and the 50% growth inhibitory concentration (IC50) was 0.6 microg/ml.
      We also demonstrated applications of cell type-specific Sindbis virus-mediated
      antigen-antibody targeting of the HSV-TK/GCV system in vitro. Sindbis virus
      containing the HSV-TK gene packaged in a helper virus displaying the IgG-binding
      domain of protein A on its envelope could infect various tumor cell lines in the
      presence of specific antibodies that recognize antigens on their surfaces. HSV-TK
      transduced tumor cell lines exhibited sensitivity to GCV. Our data suggest the
      potential for targeted gene therapy of the HSV-TK/GCV system using a cell type
      specific recombinant Sindbis virus vector-antibody system.

PMID- 9935241
TI  - Identification of a novel cytokeratin 19 pseudogene that may interfere with
      reverse transcriptase-polymerase chain reaction assays used to detect
      micrometastatic tumor cells.
AB  - In many recent publications, it has been claimed that reverse transcriptase
      polymerase chain reaction (RT-PCR) assays involving genes with tissue-restricted
      expression can be used for specific and sensitive detection of cancer cells in
      blood, bone marrow and lymph nodes. Many different target mRNAs have been
      evaluated for such purposes. One of the most extensively studied genes, CK19, is
      predominantly expressed in cells of epithelial origin and normally not at
      detectable levels in hematopoietic or lymphatic tissues. Based on previous
      reports on CK19 we wanted to establish a useful assay for detection of
      micrometastatic cells. RNA and DNA specimens extracted from peripheral blood
      nucleated cells of healthy volunteers, as well as cell lines positive and
      negative for CK19 expression, were used in nested RT-PCR assays. Using previously
      published primers, we found a novel pseudogene that shows a high degree of
      identity with the CK19 gene sequence, except for differences caused by 3 small
      deletions and a number of point mutations, resulting in termination codons and
      frameshifts. The gene has therefore no coding potential. Importantly, published
      primer sequences and reaction conditions used by several other groups to detect
      CK19 mRNA may have led to the amplification of this pseudogene. The data
      illustrate one of the problems that must be addressed in validating RT-PCR assays
      for micrometastasis detection, and it is suggested that previous work using CK19
      as a marker should be reassessed in view of the present finding.

PMID- 9935242
TI  - Effect of farnesyltransferase overexpression on cell growth and transformation.
AB  - A series of studies using farnesyltransferase (FTase) inhibitors that the
      inhibition of FTase function suppresses the growth of ras-transformed cells in
      vitro and in vivo. However, whether FTase is directly involved in the regulation
      of cell proliferation remains to be demonstrated. To investigate whether
      overexpression of FTase results in altered cell growth and transformation, we
      thus used NIH3T3 cells transfected with cDNA constructs of both alpha and beta
      subunits of human FTase. FTase-overexpressing cells resulted in a 3- to 13-fold
      increase in the expression of the alpha and beta subunit protein of FTase and a
      1.5- to 3-fold increase in the level of the enzyme activity compared with
      untransfected NIH3T3 cells or vector-transfected cells. Further investigations
      using metabolic labeling indicated that farnesylation of Ras was enhanced in
      FTase-overexpressing cells. Insulin-like growth factor-I, platelet-derived growth
      factor (PDGF), and basic fibroblast growth factor (bFGF) more potently enhanced
      DNA synthesis and anchorage-dependent growth in FTase-overexpressing cells than
      in control cells, in a dose-dependent manner. In particular, PDGF and bFGF also
      induced dose-dependently enhanced colony formation in soft agar in FTase
      overexpressing cells. Furthermore, in FTase-transfectants, bFGF stimulated high
      activation of mitogen-activated protein kinase. Interestingly, FTase
      transfectants developed progressive tumors in nude mice. Light and electron
      microscopy showed that the tumors were characteristic of fibrosarcoma, which were
      distinct from v-ras-induced tumors. Overexpression of FTase in NIH3T3 cells thus
      amplifies growth-factor-mediated cell growth and transformation, and FTase
      overexpressing cells form tumors in nude mice.

PMID- 9935243
TI  - Therapy of a xenografted human colonic carcinoma using cisplatin or doxorubicin
      encapsulated in long-circulating pegylated stealth liposomes.
AB  - We compared the therapeutic effects of low doses of cisplatin and doxorubicin
      hydrochloride encapsulated in long-circulating liposomes composed of
      cholesterol/hydrogenated soy phosphatidylcholine-polyethylene glycol-distearoyl
      phosphatidyl-ethanolamine. The encapsulation of cisplatin and doxorubicin in
      these liposomes made ineffectively low doses of the free drugs able to inhibit
      the growth of and affect cures of a human colonic carcinoma growing in nude mice.
      Liposome-encapsulated cisplatin had minor systemic toxic side effects indicated
      by an average 9% weight loss which was recovered 3-4 weeks after the last
      treatment. Toxicity was not observed in mice treated with liposome-encapsulated
      doxorubicin.

PMID- 9935244
TI  - Tumor-growth inhibition with bispecific antibody fragments in a syngeneic mouse
      melanoma model: the role of targeted T-cell co-stimulation via CD28.
AB  - The ability of bispecific antibodies with anti-tumor x anti-CD3 specificity to
      mediate the killing of tumor cells by activated T cells has been demonstrated in
      many in vitro experiments. Moreover, long-term survival of lymphoma-bearing mice
      has been observed after treatment with such reagents. The therapeutic effect of
      bispecific antibodies in solid-tumor models has been less impressive, in
      particular if fragmented antibodies were used to avoid systemic T-cell activation
      by bispecific constructs binding to Fc-receptor-positive cells. Here we report
      that bispecific anti-tumor x anti-CD3-fragments markedly inhibit intraperitoneal
      as well as pulmonary tumor growth in mice inoculated with B16 melanoma cells,
      resulting in the long-term survival of animals. Therapeutic success critically
      depends on the number of recruitable effector cells at the site of tumor growth.
      A second bispecific construct triggering the co-stimulatory CD28-molecule on the
      T-cell surface increased tumor-cell killing in vitro and in vivo, despite rather
      low avidity of this reagent to mouse T cells. Finally, long-term-surviving
      animals showed improved survival after i.v. rechallenge with tumor cells,
      indicating that bispecific antibodies are capable of inducing long-lasting
      protective immunity.

PMID- 9935246
TI  - Potentiation of cytotoxicity and radiosensitization of (E)-2-deoxy-2'
      (fluoromethylene) cytidine by pentoxifylline in vitro.
AB  - (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC), a novel inhibitor of
      ribonucleotide-diphosphate reductase, has been shown to have anti-tumor activity
      against solid tumors and sensitize tumor cells to ionizing radiation.
      Pentoxifylline (PTX) can potentiate the cell killing induced by DNA-damaging
      agents through abrogation of DNA-damage-dependent G2 checkpoint. We investigated
      the cytotoxic, radiosensitizing and cell-cycle effects of FMdC and PTX in a human
      colon-cancer cell line WiDr. PTX at 0.25-1.0 mM enhanced the cytotoxicity of FMdC
      and lowered the IC50 of FMdC from 79 +/- 0.1 to 31.2 +/- 2.1 nM, as determined by
      MTT assay. Using clonogenic assay, pre-irradiation exposure of exponentially
      growing WiDr cells to 30 nM FMdC for 48 hr or post-irradiation to 0.5 to 1.0 mM
      PTX alone resulted in an increase in radiation-induced cytotoxicity. Moreover,
      there was a significant change of the radiosensitization if both drugs were
      combined as compared with the effect of either drug alone. Cell-cycle analysis
      showed that treatment with nanomolar FMdC resulted in S-phase accumulation and
      that such an S-phase arrest can be abrogated by PTX. Treatment with FMdC prior to
      radiation increased post-irradiation-induced G2 arrest, and such G2 accumulation
      was also abrogated by PTX. These results suggest that pharmacological abrogation
      of S and G2 checkpoints by PTX may provide an effective strategy for enhancing
      the cytotoxic and radiosensitizing effects of FMdC.

PMID- 9935245
TI  - Frequent deregulation of p16 and the p16/G1 cell cycle-regulatory pathway in
      neuroblastoma.
AB  - Alterations of the p16 gene in neuroblastoma are very rare. Pronounced expression
      of p16 at both the transcript and protein levels, however, was observed in 7 of
      19 (39%) neuroblastoma cell lines and 2 of 6 (33%) primary neuroblastoma samples.
      As p16 expression is tightly controlled in a feedback loop with Rb, we
      investigated the possibility that changes in p16 expression were reflective of
      alterations of the downstream components in the G1 regulatory pathway. Two cell
      lines and one primary sample highly expressing p16 were shown to harbor CDK4
      amplification. The cyclin D2 gene was infrequently expressed in neuroblastoma
      cell lines and did not correlate with p16 expression. Slight variations in the
      expression of CDK6, cyclins D1, D3 and E; and E2F1 and E2F2 among the cell lines
      were observed, without apparent correlation with p16 status. No mutations to the
      p16-binding site of CDK4 and CDK6 nor any mutations to the coding region of p16
      itself were identified in neuroblastoma cell lines. Despite frequent N-myc
      amplification in these cell lines, no relationship with this gene was observed
      either. All cell lines contained Rb protein with varying degrees of
      phosphorylation, which bears no correlation with p16 expression. Overall,
      alterations of the G1 pathway in neuroblastoma included relatively frequent p16
      expression and infrequent CDK4 amplification and cyclin D2 expression. Despite a
      reported feedback relationship between p16 expression and Rb/G1 deregulation, p16
      expression in neuroblastoma cell lines is independent of Rb gene and
      phosphorylation status and, in contrast to other cell lines where expression of
      p16 leads to G1/S arrest, neuroblastoma cell lines proliferate in the presence of
      elevated levels of p16.

PMID- 9935247
TI  - Visual inspection with acetic acid in the early detection of cervical cancer and
      precursors.

PMID- 9935248
TI  - Antimicrobial therapy for surgical prophylaxis and for intra-abdominal and
      gynecologic infections.

PMID- 9935249
TI  - Overview of quinolones in the treatment and prevention of surgical infection.
AB  - Postoperative infection remains a complication of surgical procedures, resulting
      in increased morbidity, mortality, and cost. The frequent polymicrobial etiology
      and emerging patterns of resistance continue to compromise cure rates. Although
      quinolones have many attractive properties for the surgical setting, combination
      therapy is routinely indicated for appropriate coverage. Advanced-generation
      quinolones, such as trovafloxacin, offer an increased antimicrobial spectrum,
      including activity against important surgical pathogens, and longer elimination
      half-lives. These newer agents may be used intravenously or orally as once-daily
      single-agent therapy for surgical prophylaxis, and in place of combination
      therapy for complex intra-abdominal and pelvic infections.

PMID- 9935250
TI  - Pharmacokinetics and metabolism of single oral doses of trovafloxacin.
AB  - Trovafloxacin, a new fluoronaphthyridone derivative related to fluoroquinolone
      antimicrobial drugs, has demonstrated the following characteristics: significant
      gram-positive and gram-negative activity; significant activity against anaerobes
      and atypical respiratory pathogens; approximately 11-hour elimination half-life,
      permitting once-daily administration; and good tissue penetration. Because <10%
      of an orally administered dose is recovered in urine as unchanged drug, the
      predominant route of trovafloxacin elimination appears to be nonrenal. The two
      studies described in this review examined the metabolism and excretion of
      trovafloxacin and compared the time course and concentrations of trovafloxacin
      and its metabolites in bile to those in serum. In the first study, four healthy
      male volunteers received a single, oral 200-mg dose of radiolabeled
      trovafloxacin. In the second study, three patients with indwelling nasobiliary
      tubes received a single 200-mg dose of trovafloxacin. Samples of blood, urine,
      bile, and feces were collected. Trovafloxacin in urine and serum was analyzed by
      high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection and
      in bile by HPLC-mass spectroscopy (MS). Levels of the N-acetyl metabolite in bile
      were determined by HPLC/UV/MS. Metabolites in serum, urine, and feces were
      determined by reverse-phase HPLC/MS, and radioactivity in these samples was
      assayed by liquid scintillation counting. In the first study, 63.3% and 23.1% of
      total radioactivity were recovered in feces and urine, respectively, with most of
      the radioactivity in urine in the form of the ester glucuronide metabolite
      (12.8%) and unchanged trovafloxacin (5.9%). Unchanged drug, the N-acetyl
      metabolite, and the N-sulfate of trovafloxacin accounted for 43.2%, 9.2%, and
      3.9%, respectively, of the radioactivity in feces. In the second study, biliary
      trovafloxacin concentrations were highest between 1.5 and 10 hours postdose, and
      the maximum concentrations ranged from 18.9 to 37.9 microg/mL. The mean
      bile:serum ratio of trovafloxacin was 14.9, and the biliary concentration of
      parent drug was higher than that of its N-acetyl metabolite. In both studies,
      trovafloxacin was well tolerated, with no discontinuations due to adverse events.
      The pharmacokinetic profile of trovafloxacin in serum was consistent in healthy
      subjects and in individuals who had undergone recent hepatobiliary surgery.
      Trovafloxacin is metabolized primarily by the liver, through phase II metabolism
      (glucuronidation 13.2%, N-acetylation 10.4%, and N-sulfoconjugation 4.1%);
      minimal oxidative metabolism was detected. Renal elimination accounted for <10%
      of the administered dose. The high bile to serum ratio and higher trovafloxacin
      concentrations relative to metabolite concentrations are consistent with nonrenal
      elimination. These pharmacokinetic and pharmacodynamic results, together with a
      broad antimicrobial spectrum, long 11-hour elimination half-life, and low drug
      interaction potential, suggest that trovafloxacin may be particularly appropriate
      for use in the surgical setting.

PMID- 9935251
TI  - Concentrations of trovafloxacin in colonic tissue and peritoneal fluid after
      intravenous infusion of the prodrug alatrofloxacin in patients undergoing
      colorectal surgery.
AB  - BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose
      pharmacokinetics and in vitro activity suggest that it is well suited for
      antibiotic prophylaxis in elective colorectal surgery. Alatrofloxacin is a
      prodrug that is rapidly hydrolyzed to trovafloxacin in the body. METHODS: Twelve
      patients received a single dose of alatrofloxacin equivalent to 200 mg
      trovafloxacin by intravenous infusion over 1 hour. Surgery was started at various
      time points relative to infusion time to allow determination of trovafloxacin
      concentrations in serum, colonic tissue, and peritoneal fluid as a function of
      time. RESULTS: The concentration in the earliest colonic tissue sample (1.4 hours
      after dosing) was 1.4 microg/g. The maximum colonic tissue concentration was 2.8
      microg/g in a sample taken 2 hours after dosing. Colonic tissue/serum
      concentration ratios in samples taken 2-10 hours after the end of infusion ranged
      from 0.8 to 1.47. Concentrations of trovafloxacin in peritoneal fluid ranged from
      below the level of quantitation to 2.1 microg/mL at the time of colonic tissue
      sampling and from below the level of quantitation to 2.5 microg/mL at the time of
      wound closure. Alatrofloxacin was well tolerated. CONCLUSIONS: After a single
      intravenous dose of alatrofloxacin equivalent to 200 mg trovafloxacin,
      trovafloxacin is distributed rapidly into colonic tissue and peritoneal fluids.
      Tissue concentrations approximate serum concentrations and decline in parallel
      for up to 10 hours after dosing.

PMID- 9935252
TI  - Penetration of trovafloxacin into gynecologic tissues.
AB  - BACKGROUND: This randomized open-label study assessed the penetration into
      gynecologic tissues of trovafloxacin, a new broad-spectrum, fourth-generation
      fluoroquinolone with in vitro activity against anaerobes, gram-positive, gram
      negative, and atypical pathogens. METHODS: Women undergoing hysterectomy or
      hysterectomy and adnexectomy received 200 mg trovafloxacin orally before surgery
      as a single dose or as multiple doses. Samples of genital tract tissue and serum
      were obtained simultaneously during surgery. RESULTS: In the single-dose group,
      trovafloxacin concentrations in genital tract tissues were measurable for up to
      30 hours. Tissue concentrations of trovafloxacin after multiple doses were
      comparable to those after single doses. Mean tissue: serum concentration ratios
      after a single dose were greatest in the ovary (1.6 microg/g) and comparable in
      uterus, myometrium, cervix, and fallopian tubes (0.5 to 0.7 microg/g). Adverse
      events after a single dose were minor. CONCLUSIONS: A daily dose of 200 mg
      trovafloxacin produces gynecologic tissue concentrations that persist for up to
      30 hours at levels necessary to prevent or treat pelvic infections. This dosing
      regimen is well tolerated.

PMID- 9935253
TI  - The bioavailability of nasogastric versus tablet-form oral trovafloxacin in
      healthy subjects.
AB  - BACKGROUND: Patients in the hospital, as well as those in home care settings,
      often require nutritional supplementation with enteral feeding solutions. In
      addition, patients with serious infections who are clinically unstable often
      cannot maintain adequate intake by mouth and may require an alternative to oral
      antibiotic administration. However, delivery of crushed oral formulations of
      drugs via nasogastric tubes is often carried out without adequate bioavailability
      data, and this method of administration may not always be equivalent to oral drug
      delivery. METHODS: In an open-label, randomized, four-period, four-treatment,
      cross-over study, 24 healthy volunteers were given one dose of each of the
      following treatments, with a 7-day wash-out between dosing periods: Treatment A:
      two 100-mg trovafloxacin tablets given orally with 240 mL water; Treatment B: two
      crushed 100-mg trovafloxacin tablets suspended in water and administered through
      a nasogastric tube into the stomach; Treatment C: two crushed 100-mg
      trovafloxacin tablets suspended in water and administered through a nasogastric
      tube into the duodenum; or Treatment D: two crushed 100-mg trovafloxacin tablets
      suspended in water and given through a nasogastric tube into the stomach
      concomitantly with an enteral feeding solution (240 mL full-strength Osmolite).
      RESULTS: Pharmacokinetic analyses showed that the bioavailability of
      trovafloxacin after administration of crushed tablets into the stomach with or
      without concomitant enteral feeding was not significantly different from that of
      the orally administered whole tablets: the 90% confidence limits of the area
      under the concentration-time curve (AUC(0-infinity)) for Treatment B versus
      Treatment A (91.3%, 109.5%) and Treatment D versus Treatment A (91.6%, 109.9%)
      were well within the bioequivalence criteria of 80% to 125%. Results of analysis
      of variance (ANOVA) indicated no significant sequence, period, or treatment-by
      period interaction effects. Administration of trovafloxacin into the duodenum
      (Treatment C) resulted in reduced systemic exposure to trovafloxacin, with a 31%
      decrease in AUC(0-infinity) and a 30% decrease in peak serum concentration (Cmax)
      compared to oral administration. Time to peak serum concentration (Tmax) was 1.7
      hours after oral administration of trovafloxacin and 1.1 hours after
      administration directly into the stomach or duodenum through a nasogastric tube
      in the absence of concomitant enteral feeding. All four treatments were well
      tolerated; no participant discontinued the study due to adverse events and no
      serious adverse events were reported. CONCLUSIONS: These results showed that
      administration of crushed trovafloxacin tablets through a nasogastric tube into
      the stomach, with or without concomitant enteral feeding, achieves absorption and
      tolerability comparable to those of orally administered trovafloxacin tablets.

PMID- 9935254
TI  - A double-blind, placebo-controlled, parallel group study of oral trovafloxacin on
      bowel microflora in healthy male volunteers.
AB  - BACKGROUND: Treatment with oral antibiotic drugs generally influences normal
      fecal flora. These changes can be both beneficial (eg, elimination of aerobic,
      gram-negative bacilli) and detrimental (eg, the appearance of resistant
      pathogenic micro-organisms). Trovafloxacin, a new fluoroquinolone with in vitro
      activity against anaerobes, and gram-negative, gram-positive, and atypical
      pathogens, is a potentially beneficial antimicrobial for bowel sterilization.
      This double-blind trial investigated the effect of trovafloxacin on the normal
      microbial bowel flora of healthy male subjects. METHODS: Subjects were randomized
      (in a 2:1 ratio) to receive either 200 mg trovafloxacin once daily for 10 days or
      a matching placebo. Fecal samples were collected at two baseline occasions, on
      visit days 4, 7, 10, and 17, and at follow-up. Bacterial species were identified
      and quantified in the fecal samples. RESULTS: Twelve subjects received the active
      drug and seven received placebo. No Enterobacteriaceae were found in samples from
      days 4 to 10 in subjects receiving trovafloxacin. No changes in
      Enterobacteriaceae were found throughout the study in subjects receiving placebo.
      Incidental Enterobacteriaceae were isolated from subjects in the trovafloxacin
      group at the end of the study. No clinically significant differences were found
      in either group with respect to prevalence, appearance, or disappearance of
      aerobic gram-positive cocci, anaerobic bacteria, or yeasts. All tested
      Enterobacteriaceae were highly susceptible to trovafloxacin. No increase in
      minimum inhibitory concentration values was seen in day 17 and follow-up samples
      for isolated Escherichia coli strains. No Clostridium difficile was found in day
      17 or follow-up samples from subjects in the trovafloxacin group. All tests for
      clostridium toxin were negative. CONCLUSIONS: During the treatment period, E.
      coli could not be cultured from the feces of the 12 healthy subjects receiving
      200 mg trovafloxacin daily during days 4 to 10. All isolated Enterobacteriaceae
      were susceptible to trovafloxacin and no changes in susceptibility were found
      after the treatment period. In subjects treated with trovafloxacin, the
      prevalence and number of gram-positive bacteria were rapidly reduced.
      Trovafloxacin is able to selectively and reversibly suppress bowel flora.

PMID- 9935255
TI  - The pharmacokinetic effects of coadministration of morphine and trovafloxacin in
      healthy subjects.
AB  - BACKGROUND: Morphine and antibiotics are frequently coadministered in the
      surgical setting. These agents may interact, reducing the efficacy of the
      antibiotic or increasing the toxicity of morphine. It is therefore important to
      determine whether antibiotics that might be used for surgical prophylaxis have
      the potential to change the pharmacokinetics of morphine. It is equally important
      to learn whether morphine affects the plasma levels of antibiotics and thus may
      potentially influence their efficacy or tolerability. METHODS: This open,
      randomized, placebo-controlled, three-treatment, three-period cross-over study
      enrolled 19 healthy volunteers. Oral trovafloxacin (200 mg), a novel
      fluoroquinolone antibiotic, and intravenous morphine (0.15 mg/kg) were
      coadministered, and the effects on the pharmacokinetics of each drug and on
      changes in the pharmacologic action of morphine, estimated from its effects on
      respiratory rate and level of sedation, were examined. RESULTS: When
      trovafloxacin was coadministered with morphine, the half-life of trovafloxacin
      was unchanged; however, the ratio of the area under the serum concentration
      versus time curve (AUC(0-infinity)) estimates for trovafloxacin/morphine versus
      trovafloxacin/placebo was 63.8% (95% confidence interval [CI], 40.7% to 100.3%),
      indicating a 36% reduction in the bioavailability of trovafloxacin. The ratio of
      the mean maximum serum concentration (Cmax) estimates of trovafloxacin for the
      two treatments was 53.8% (95% CI: 36.1% to 80.1%), indicating a 46% reduction in
      Cmax. The time to Cmax was delayed by 4 hours. With trovafloxacin
      coadministration, there were no statistically significant changes in either the
      mean relative bioavailability of morphine or that of its metabolite, 6beta
      glucuronide-morphine. Coadministration of trovafloxacin did not exacerbate the
      reduction in respiratory rate or increase the number of side effects associated
      with morphine administration. CONCLUSIONS: Coadministration of trovafloxacin and
      morphine reduces the bioavailability and maximum serum concentrations of
      trovafloxacin. However, elimination of oral trovafloxacin is not impaired,
      suggesting that the efficacy of trovafloxacin could be maintained in many
      patients who receive concomitant morphine. Morphine plasma levels and
      pharmacologic effects are not significantly altered by coadministration of
      trovafloxacin. Despite their similar metabolic pathways, the
      trovafloxacin/morphine combination neither exacerbates the respiratory depressant
      effects of morphine nor increases the frequency of side effects when compared
      with placebo/morphine treatment. These results suggest that the efficacy of
      trovafloxacin may be maintained when coadministered with morphine. Concurrent
      administration of trovafloxacin and morphine is unlikely to alter the
      pharmacologic effects of morphine.

PMID- 9935256
TI  - Pharmacodynamics and microbiology of trovafloxacin in animal models of surgical
      infection.
AB  - Trovafloxacin provides broad in vitro and in vivo coverage of the aerobic and
      anaerobic pathogens found frequently in surgical infections. In vitro
      susceptibility testing indicated that trovafloxacin inhibited gram-positive
      staphylococci and enterococci, numerous gram-negative organisms, including
      Escherichia coli, and anaerobic pathogens, such as Bacteroides fragilis.
      Trovafloxacin protected mice from lethal infections induced by gram-negative or
      gram-positive organisms, even when these organisms were inoculated in combination
      with B. fragilis. Trovafloxacin protected rats in models of intra-abdominal
      sepsis induced by inoculation with E. coli and B. fragilis or with multiple
      aerobic and anaerobic pathogens. In these experimental models, trovafloxacin
      protected rats from lethal infection, reduced intra-abdominal abscess formation,
      and inhibited bacterial growth. Drug concentrations were greater in intra
      abdominal abscesses than in serum, reflecting the good tissue penetration of
      trovafloxacin. These results indicate that trovafloxacin may be effective in
      prophylaxis and treatment of mixed infections in surgical patients.

PMID- 9935257
TI  - Double-blind comparison of single-dose alatrofloxacin and cefotetan as
      prophylaxis of infection following elective colorectal surgery. Trovafloxacin
      Surgical Group.
AB  - BACKGROUND: Alatrofloxacin, the prodrug of trovafloxacin, is a novel
      fluoroquinolone antimicrobial agent with a broad spectrum, including activity
      against gram-positive and gram-negative aerobes and anaerobes. Its
      pharmacokinetic properties (long half-life, excellent tissue distribution, and
      good safety profile) suggest a role in surgical prophylaxis. This prospective,
      multicenter, double-blind trial compared alatrofloxacin with cefotetan, an
      approved drug for surgical prophylaxis, in reducing postoperative infections.
      METHODS: The efficacy and safety of a single 200-mg intravenous dose of
      alatrofloxacin were compared to a single 2-g intravenous dose of cefotetan in 492
      patients undergoing elective colorectal surgery. The efficacy of alatrofloxacin
      as a prophylaxis for wound, intra-abdominal, or remote-site postoperative
      infectious complications was compared with cefotetan in 317 clinically evaluable
      patients; 161 received alatrofloxacin and 156 received cefotetan. The patients
      were monitored for infections and safety for 30 days postoperatively. RESULTS: No
      statistically significant between-treatment difference was detected in successful
      clinical response rates at the end of the study (72% for each group). The
      incidence of primary wound infections at the time of hospital discharge was also
      similar: 21% in patients treated with alatrofloxacin and 18% in those treated
      with cefotetan. Safety, established by the incidence of adverse events, did not
      differ statistically between the groups. CONCLUSIONS: A single intravenous dose
      of alatrofloxacin given within 4 hours prior to surgery was as effective as an
      intravenous dose of cefotetan in the prevention of postoperative infectious
      complications in patients undergoing elective colorectal surgery. The safety
      profiles of the two medications were similar.

PMID- 9935258
TI  - Trovafloxacin in the treatment of intra-abdominal infections: results of a double
      blind, multicenter comparison with imipenem/cilastatin. Trovafloxacin Surgical
      Group.
AB  - BACKGROUND: Trovafloxacin, a new broad-spectrum fourth-generation quinolone, has
      in vitro activity against most gram-negative and gram-positive anaerobes and
      aerobes. Trovafloxacin is available as both an intravenous formulation,
      alatrofloxacin, and a single daily oral tablet. Excellent tissue pharmacokinetics
      and oral bioavailability suggest usefulness in the treatment of complicated intra
      abdominal infections. Thus, the efficacy of alatrofloxacin followed by oral
      trovafloxacin was compared with the standard regimen of intravenous
      imipenem/cilastatin followed by oral amoxicillin/clavulanic acid in this
      prospective, multicenter, double-blind trial. METHODS: Patients were randomized
      to receive either 300 mg alatrofloxacin daily followed by 200 mg oral
      trovafloxacin daily or 1 g imipenem/cilastatin intravenously thrice daily
      followed by 500 mg oral amoxicillin/clavulanic acid thrice daily for up to 14
      days following surgical intervention of a documented intra-abdominal infection.
      Efficacy was assessed at the end of therapy and at follow-up (day 30). RESULTS:
      At the end of the study, cure or improvement occurred in 83% (129/156) and 84%
      (127/152) of clinically evaluable patients in the trovafloxacin and comparative
      groups, respectively. Pathogen eradication rates, adverse-event profiles, and
      significant laboratory abnormalities were comparable between groups. CONCLUSION:
      Intravenous alatrofloxacin with or without oral trovafloxacin was as effective as
      intravenous imipenem/cilastatin followed by oral amoxicillin/clavulanic acid in
      complicated intra-abdominal infections.

PMID- 9935259
TI  - Oral trovafloxacin compared with intravenous cefoxitin in the prevention of
      bacterial infection after elective vaginal or abdominal hysterectomy for
      nonmalignant disease. Trovafloxacin Surgical Group.
AB  - BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose
      pharmacokinetics and in vitro activity suggest that it is well suited for
      antibiotic prophylaxis in elective hysterectomy. METHODS: In a randomized, double
      blind, multicenter study, parallel groups of women 18 years of age or older
      received either 200 mg trovafloxacin by mouth and intravenous (i.v.) placebo or 2
      g cefoxitin by i.v. infusion and placebo by mouth before elective vaginal or
      abdominal hysterectomy for nonmalignant disease. RESULTS: In the 103 and 97
      patients in the trovafloxacin and cefoxitin groups, respectively, who were
      evaluable for efficacy, the prophylactic success rates at hospital discharge (96%
      in both groups) and 30 +/- 6 days after hysterectomy (88% and 91% in the
      trovafloxacin and cefoxitin groups, respectively) were statistically equivalent.
      Both antibiotics were well tolerated. CONCLUSION: A single oral 200 mg dose of
      trovafloxacin is as effective and safe as a standard cefoxitin parenteral regimen
      in the prevention of primary bacterial infection after elective vaginal or
      abdominal hysterectomy for nonmalignant disease.

PMID- 9935260
TI  - Treatment of acute gynecologic infections with trovafloxacin. Trovafloxacin
      Surgical Group.
AB  - BACKGROUND: Trovafloxacin, a broad-spectrum fourth-generation quinolone with gram
      positive and gram-negative aerobic and anaerobic bacterial activity, is available
      in oral and intravenous formulations. The objective of this prospective,
      multicenter, double-blind, randomized study was to compare the efficacy of
      trovafloxacin with that of cefoxitin, an approved drug for treatment of acute
      gynecologic infections, together with amoxicillin/clavulanic acid as oral follow
      on treatment. METHODS: Patients with a clinical diagnosis of acute pelvic
      infection received either intravenous alatrofloxacin with oral trovafloxacin
      follow-on (trovafloxacin) or a combined regimen of cefoxitin followed by
      amoxicillin/clavulanic acid for a maximum of 14 days. The primary endpoint was
      clinical response to therapy on follow-up at day 30. RESULTS: Clinical success
      rates were comparable between the trovafloxacin (n = 107) and comparative (n =
      119) groups at study end (90% vs. 86%, respectively; 95% confidence interval, 
      4.5, 12.5). Among clinically evaluable patients, clinical success rates for
      infections involving Enterococcus species were higher with trovafloxacin than
      with the comparative regimen at the end of treatment (96% and 85%) and at study
      end (96% and 86%). CONCLUSION: Intravenous alatrofloxacin followed by oral
      trovafloxacin for a maximum of 14 days of total therapy was efficacious in the
      treatment of acute pelvic infections.

PMID- 9935261
TI  - Safety and tolerability of intravenous-to-oral treatment and single-dose
      intravenous or oral prophylaxis with trovafloxacin.
AB  - BACKGROUND: The new fourth-generation fluoroquinolone, trovafloxacin, is active
      in vitro against gram-positive and gram-negative organisms, atypical pathogens,
      and anaerobes, and has pharmacokinetics permitting once-daily intravenous or oral
      dosing. Safety/tolerability data from phase II/III clinical trials of sequential
      intravenous alatrofloxacin to oral trovafloxacin and single-dose intravenous or
      oral prophylaxis are summarized. METHODS: All trials were double-blind,
      randomized, and multicenter. In multidose trials with alatrofloxacin, 1,257
      patients requiring initial intravenous therapy received once-daily alatrofloxacin
      (trovafloxacin prodrug, 200 or 300 mg/day) followed by oral 200 mg/day
      trovafloxacin. An additional 444 patients received a single alatrofloxacin or
      trovafloxacin dose prophylactically for surgical procedures. RESULTS: Therapy
      with alatrofloxacin was well tolerated. The most common treatment-related adverse
      events in studies of intravenous alatrofloxacin followed by oral trovafloxacin
      were nausea, headache, insertion site reaction, and dizziness. In single-dose
      intravenous or oral prophylaxis studies, insertion-site reaction, pruritus, and
      insertion-site pain were the most common treatment-related adverse events. No
      serious quinolone toxicity or drug interactions were reported. The incidence of
      serious treatment-related adverse events was < 1% in both the alatrofloxacin and
      comparator groups. In comparative trials, mortality due to all causes after
      trovafloxacin was similar to that after comparative agents; there was no
      mortality related to trovafloxacin administration. CONCLUSION: In this large
      patient sample, intravenous alatrofloxacin followed by oral trovafloxacin was
      safe and well tolerated. Serious adverse events, such as phototoxicity,
      cardiovascular toxicity, and hemolytic anemia associated with older
      fluoroquinolones, were not noted with trovafloxacin. No interactions of
      trovafloxacin with other drugs were reported. The safety and tolerability of
      trovafloxacin, along with in vitro activity against key pathogens and
      pharmacokinetics permitting once-daily administration, support its oral and
      intravenous use in patients with obstetric, gynecologic, and intra-abdominal
      infections as well as for prophylaxis of surgical infection.

PMID- 9935262
TI  - Antimicrobial agents for the prevention and treatment of abdominal infections: a
      new generation?

PMID- 9935263
TI  - Involvement of stretch-sensitive calcium flux in mechanical transduction in
      visceral afferents.
AB  - The spinal and vagal visceral innervation to the gastrointestinal tract contains
      mechanosensitive afferents that are activated by contraction, distension of
      smooth muscle or movement in the receptive field. The mechanism by which free
      nerve endings detect changes in smooth muscle tension is not clear. The present
      study investigated the effects of mechanical stimulation on dorsal root ganglion
      neurons in vitro. Neurons were cultured using standard techniques and used in
      experiments after 24-72 h. Intracellular calcium [Ca2+]i was visualized using a
      video microscopic technique (Attoflour) in Fura-2 loaded neurons. DRG neurons
      innervating the stomach or colon were identified by the presence of a retrograde
      tracer, dextran-conjugated Texas Red, injected into the visceral wall 14-28 days
      previously. Increases in [Ca2+]i were measured in response to transient (0.5 s)
      mechanical stimulation of the cell soma using a flame polished probe.
      Approximately 25% of the whole population of DRG neurons (n = 199) were
      mechanosensitive, showing a transient rise in [Ca2+]i. In labeled afferents (n =
      12), approximately 40% of neurons were mechanosensitive. The increase in [Ca2+]i
      in response to mechanical stimulation was reduced (100 microM) or abolished (250
      microM) by superfusion with gadolinium or by removal of extracellular calcium.
      Cell somata of visceral spinal afferents show a stretch-sensitive calcium flux
      that may be involved in sensory transduction of mechanical stimuli that lead to
      autonomic and sensory reflexes.

PMID- 9935264
TI  - Bradykinin B2-receptors mediate the pressor and renal hemodynamic effects of
      intravenous bradykinin in conscious rats.
AB  - Bradykinin (BK) is a peptide which evokes remarkably different changes in
      cardiovascular function. Systemic bolus injection of BK results in a rapid drop
      in blood pressure via an endothelium-dependent mechanism. On the other hand,
      local administration of BK can activate a powerful pressor reflex by stimulating
      afferent nerves located in the abdominal viscera, the heart, and the kidney. In
      the present study, the cardiovascular and renal hemodynamic effects during
      sustained (intravenous infusion) and transient (intravenous bolus injection)
      elevations in circulating BK were characterized and the receptor mechanism
      eliciting these effects was investigated. Mean arterial pressure (MAP), heart
      rate (HR), and renal blood flow (RBF) were recorded from conscious unrestrained
      rats while five-point cumulative dose-response curves were constructed during
      infusion or bolus injection of BK (5-80 microg kg(-1)). Infusion of BK produced
      dose-dependent increases in MAP (maximum response = 27 +/- 3 mmHg) accompanied by
      a significant tachycardia (maximum response = 159 +/- 20 bpm), a 28 +/- 6%
      increase in RBF, and no changes in renal vascular resistance (RVR). The BK
      induced increases in MAP, HR, and RBF were abolished after treatment with a
      ganglion blocker (maximum responses: MAP = 2 +/- 3 mmHg, HR = 13 +/- 4 bpm, RBF =
      4 +/- 2%) or with an agent which blocks B2-receptors (maximum responses: MAP = 1
      +/- 1 mmHg, HR = 6 +/- 5 bpm, RBF = 6 +/- 2%). In marked contrast, bolus
      administration of BK resulted in hypotensive responses (maximum decline in MAP = 
      37 +/- 4 mmHg), reflex tachycardia (maximum increase in HR = 45 +/- 9 bpm),
      increases in RBF (maximum response = 13 +/- 4%), and significant reductions in
      RVR (maximum response = 38 +/- 5%). These responses were also prevented when B2
      receptors were blocked (maximum responses: MAP = 3 +/- 2 mmHg, HR = 17 +/- 6 bpm,
      RBF = 3 +/- 3%, RVR = 9 +/- 4%). In summary, BK infusions activated a
      cardiopressor reflex while BK injections caused hypotension. These opposite
      effects were both mediated via B2-receptors. These findings suggest that BK can
      have complex effects on the cardiovascular system that may be dependent on the
      sites, magnitude, and duration of elevated BK concentrations.

PMID- 9935265
TI  - Modulation of nicotinic acetylcholine receptor activity in submucous neurons by
      intracellular messengers.
AB  - The effects on acetylcholine-induced membrane currents (ACh currents), produced
      by agents known to modify the activity of intracellular messengers, were studied
      in the neurons of the guinea-pig ileum submucous plexus (SMP) using a whole-cell
      patch clamp recording method. The ACh currents were not affected by forskolin,
      the adenylate cyclase activator, regardless of whether or not ATP and GTP were
      present in the intracellular solution, and by phorbol 12-myristate 13-acetate,
      the protein kinase C activator. The ACh currents were strongly suppressed by
      thapsigargin, the microsomal calcium ATPase inhibitor, and genistein, the
      tyrosine protein kinase inhibitor. They were also suppressed by 3-isobutyl-1
      methylxanthine, the cyclic-AMP phosphodiesterase inhibitor, regardless of the
      presence of forskolin in the extracellular solution and ATP and GTP in the
      intracellular solution. In addition, the currents were suppressed by activation
      of P2 purinoceptors with ATP, which could not be explained by a direct effect of
      ATP on nicotinic acetylcholine receptors (nAChRs). Reactive blue 2, the P2y
      purinoceptor antagonist, did not abolish inhibition of the ACh current by ATP.
      Alpha,beta-Imido-ATP and adenosine caused no membrane current responses and did
      not influence the ACh currents. These results suggest that the activity of the
      nAChRs in the SMP neurons is strongly suppressed by raised intracellular Ca2+
      level, without involvement of protein kinases A and C, and may involve the
      participation of tyrosine kinase. The activity of nAChRs is also influenced by
      the activity of P2 purinoceptors; the mechanisms responsible for this influence
      are not yet clear. So, the activity of the SMP neuronal nAChRs is relatively
      independent on the intracellular signaling known to influence many other groups
      of transmitter-gated receptors of neuronal membrane.

PMID- 9935266
TI  - Uterine contractility and blood flow are reflexively regulated by cutaneous
      afferent stimulation in anesthetized rats.
AB  - The effects of cutaneous mechanical afferent stimulation of various skin areas on
      uterine contractility and blood flow were examined in anesthetized non-pregnant
      rats. The contractility of the uterus was measured by the balloon method in the
      uterus. The uterine blood flow was measured by laser Doppler flowmetry. Noxious
      pinching stimulation of the perineum for 1 min induced an abrupt contraction of
      the uterus during stimulation. Pinching of a hindpaw or perineum and innocuous
      brushing of the perineum for 1 min increased uterine blood flow. Stimulation of
      other skin areas produced no changes in uterine contractility or blood flow. Most
      uterine responses were abolished by severance of the pelvic nerves, which
      innervated the uterus. The activity of pelvic parasympathetic efferent nerves to
      the uterus increased following perineal pinching. All these cutaneous stimulation
      induced responses of uterine contractility, blood flow and pelvic efferent nerve
      activity still existed, and were even augmented, after acute spinalization. These
      results indicate that cutaneous mechanical sensory stimulation can regulate
      uterine contractility and blood flow by a segmental spinal reflex mechanism via
      uterine parasympathetic efferent nerves.

PMID- 9935267
TI  - Effects of mental stress on cardiac and motor rhythms.
AB  - To identify whether spontaneous cardiac rhythm and voluntary motor rhythm are
      modified in parallel or influenced separately when imposing mental stress, we
      recorded simultaneously the two rhythms during finger tapping as a simple model
      of rhythmical motion in 10 healthy human subjects (6 males, 4 females each). Each
      subject performed finger tapping with an arbitrary tapping rhythm. Mental stress
      was given intermittently three times for 10-15 s at intervals of 40 s during
      tapping for 150 s. Heart rate (HR) and tapping rate (TR) and their variations
      (standard deviation; SD) during finger tapping with and without mental stress
      were compared. HR and TR increased significantly in response to mental stress
      during tapping. After mental stress was ended, HR returned rapidly to the initial
      level, but TR remained at a higher level. Moreover, SD of TR, but not SD of HR,
      during tapping was increased by mental stress. The present results indicate that
      the cardiac and motor rhythms are influenced simultaneously by mental stress.
      However, a difference was seen about the sustained effect of mental stress on the
      two rhythms.

PMID- 9935268
TI  - c-Kit immunoreactive interstitial cells in the human gastrointestinal tract.
AB  - c-Kit immunopositive cells are considered to be pacemakers and/or mediators of
      neurotransmission in the gastrointestinal tract. They also correspond to the
      interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit
      positive cells and their relation to ICs in the human gastrointestinal tract
      remain unclear. In this study we examine the distribution of c-Kit positive cells
      and their ultrastructure in normal human tissue. We then classified them and
      examined their relationship to ICs. Thirty nine samples of gut from the esophagus
      to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57
      year old and without motility disorders), were processed for
      immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit
      immunopositive cells were located in the external muscle from the lower esophagus
      to the sigmoid colon, wherever the external muscle was composed of smooth muscle
      cells, and they were classified morphologically into two groups. Cells in the
      first group were mainly spindle-shaped bipolar cells with few branches; these
      cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed
      many intermediate filaments and caveolae. The spindle-shaped cells were present
      in the esophagus, stomach and small intestine. The second group of cells were
      located only in the colon, and were multipolar or bipolar cells with numerous
      branches. Cells in the second group were also rich in caveolae and/or smooth
      endoplasmic reticulum, but intermediate filaments were not prominent. Although
      both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the
      human gut do not appear to express c-Kit immunoreactivity.

PMID- 9935269
TI  - Response of the gastric vagal afferent activity to cholecystokinin in rats
      lacking type A cholecystokinin receptors.
AB  - A systemic administration of cholecystokinin (CCK) increases gastric vagal
      afferent activity via type A CCK receptors (CCKAR). In the present study, the
      response of gastric vagal afferent activity to an intravenous administration of
      CCK was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which
      lack CCKAR, and compared with its control strain, Long-Evans Tokushima Otsuka
      (LETO) rats. The intravenous administration of 300 pmol kg(-1) and 3 nmol kg(-1)
      of CCK elicited dose-dependent increases in the gastric vagal afferent activity
      in LETO rats. The responses were not influenced by the pretreatment with L
      365,260, a type B CCK receptor (CCKBR) antagonist, while they were significantly
      diminished by pretreatment with MK-329, a CCKAR antagonist. After pretreatment
      with MK-329, 3 nmol kg(-1) (but not 300 pmol kg(-1)) of CCK still elicited a
      small but significant increase in the activity. In the OLETF rats, both 300 pmol
      kg(-1) and 3 nmol kg(-1) of CCK produced small increases in the vagal afferent
      activity, and the responses were not influenced by pretreatment with either L
      365,260 or MK-329. In addition, the systemic administration of CCK did not change
      gastric motility in the OLETF rats, indicating that the response of the vagal
      afferent activity in OLETF rats was independent of the gastric motility change.
      These results demonstrate that neither CCKAR nor CCKBR contributes to the
      response of the afferent activity of the gastric vagal nerve to a systemic
      administration of CCK in OLETF rats, suggesting an involvement of novel (non-A,
      non-B) CCK receptors.

PMID- 9935270
TI  - Effect of acute saline volume loading on renal sympathetic nerve activity in
      anaesthetised fructose-fed and fat-fed rats.
AB  - Experiments were conducted to investigate the effects of activation of
      cardiopulmonary vagal afferent nerve endings by acute saline volume expansion on
      sympathetic efferent renal nerve activity in anaesthetised fat-fed and fructose
      fed Wistar rats. Four weeks of fat feeding caused obesity in the Wistar rats
      which was associated with a mild elevation in blood pressure (118 +/- 4 mmHg vs.
      105 +/- 1 mmHg in the lean control rats, P < 0.05). Fructose feeding in Wistar
      rats for 4 weeks also elicited an elevation of blood pressure (113 +/- 4 mmHg, P
      < 0.05) and plasma glucose levels (6.3 +/- 0.3 mmol/l vs. 4.0 +/- 0.3 mmol/l lean
      control rats, P < 0.01). The fat-fed rats displayed a higher basal renal
      sympathetic nerve activity (RSNA) value when compared with the lean rats (3.9 +/-
      0.4 mV/s vs. 2.8 +/- 0.4 mV/s, P < 0.05) whereas the RSNA levels were similar in
      all the other rat groups. The power spectral analysis of RSNA showed the basal
      values of percentage power at heart rate frequency were significantly higher in
      Wistars fed ad lib (P < 0.01), rats fed on fructose for 2 or 4 weeks (P < 0.01
      and P < 0.05, respectively) and fat-fed rats (P < 0.01) when compared to the lean
      diet-controlled rats. Acute volume expansion (10% body wt) over 40 min caused
      efferent renal sympatho-inhibition in all the animal groups. The pattern and
      magnitude of response in MAP, RSNA, and power spectral analysis parameters to the
      volume expansion were similar in the lean control rats, the Wistar and fructose
      fed rats but was greater in the fat-fed rats (P < 0.05) as compared to the lean
      control rat. The profile of the reduction in percentage power at heart rate
      frequency to volume expansion was greater (P < 0.05) in the fat-fed rat than in
      the lean control rats. The present data demonstrates that the reflex efferent
      renal sympatho-inhibition to volume expansion was impaired in the diet-induced
      obese rat but not in the fructose fed rats. This suggests that a defect in the
      neuro-humoral regulation of kidney control of extracellular fluid volume is
      present which may contribute to the mild hypertension in the obese rat.

PMID- 9935271
TI  - Autonomic neuropathy associated with sicca complex.
AB  - We retrospectively studied 52 patients with sicca complex who presented primarily
      with peripheral neuropathic symptoms to assess the degree of autonomic
      involvement and its relationship to somatic neuropathy, serological tests and
      extraglandular disease. One patient presented with severe panautonomic
      dysfunction, with another six patients reporting prominent autonomic symptoms,
      and a further 40 patients having mild or asymptomatic disease. Eighty-seven
      percent of patients showed abnormalities on an autonomic reflex screen (ARS).
      Fifty-eight percent of patients showed a mixed pattern of autonomic dysfunction
      with abnormalities in two or more ARS subgroups of sudomotor, cardiovagal and
      adrenergic function. Three patients had a cholinergic autonomic neuropathy with
      sparing of adrenergic function. Tonic pupils were present in 13 patients.
      Autonomic neuropathy occurred in patients with a variety of somatic neuropathy
      subtypes, without a clear relationship between the type of autonomic neuropathy
      and the type of somatic peripheral neuropathy. Extraglandular disease was
      uncommon, occurring in only four patients. Serological abnormalities (extractable
      nuclear antigen [ENA], SS-A, SS-B) occurred in 20% of patients. We conclude that:
      (1) A wide spectrum of autonomic dysfunction is seen in sicca complex. (2) Severe
      autonomic involvement is uncommon, with most patients showing mildly symptomatic
      or asymptomatic disease. (3) Overall, characteristic patterns of autonomic
      dysfunction did not predominate, and there were no clear relationships with the
      different types of somatic peripheral neuropathy. (4) Clinical and serological
      evidence of non-neurological extraglandular disease is uncommon in this group of
      patients.

PMID- 9935272
TI  - Heart failure treatments: issues of safety versus issues of quality of life.
AB  - Congestive heart failure is an important cause of morbidity and mortality in
      western countries. The profound impact that congestive heart failure has on life
      expectancy and quality of life has been a continuous stimulus for the development
      of new drugs for the treatment of this condition. Despite favourable effects on
      (aspects of) quality of life in short term studies, several of these new agents
      have been shown to reduce survival in mortality trials. However, patients with
      severe congestive heart failure may experience such incapacitating symptoms that
      the question should be raised as to whether an improvement in quality of life
      makes the increased risk of mortality associated with these new agents
      acceptable. Drugs which improve quality of life at the expense of an increased
      risk of mortality can be of value in the treatment of patients with severe
      congestive heart failure. However, this is only the case if the probability of
      improvement in quality of life and prolongation of life expectancy for those
      using the drug exceeds the probability of improvement in quality of life and
      prolongation of life expectancy for those not using the drug. Unfortunately, most
      clinical trials in which both mortality and quality of life are evaluated fail to
      provide information on this composite probability. Despite disappointing results
      of some recent mortality trials on new pharmacological treatments of congestive
      heart failure, sound and well designed clinical trials on innovative heart
      failure treatments in which these composite probabilities are also assessed
      should be carried out.

PMID- 9935273
TI  - Does cocaine still have a role in nasal surgery?
AB  - Endonasal surgery is already very common and its importance is increasing.
      Successful anaesthesia in endonasal sinus surgery is of critical importance for
      the success of the procedure and many surgeons prefer to use cocaine for this
      purpose. However, there is a great body of evidence that suggests that use of
      cocaine, even in experienced hands, can cause rapid, unexpected and severe toxic
      reactions. Therefore, its use in endonasal surgery can no longer be recommended,
      especially since better tolerated alternatives are available for topical and
      infiltration anaesthesia. These alternatives include lidocaine (lignocaine) and
      tetracaine (pantocaine) in combination with epinephrine (adrenaline), naphazoline
      or oxymetazoline.

PMID- 9935274
TI  - Analgesic nephropathy: is it caused by multi-analgesic abuse or single substance
      use?
AB  - Analgesic nephropathy is a slowly progressive renal disease, characterised by
      renal papillary necrosis. Recently, diagnostic criteria for this disease have
      been defined based on renal computed tomography scanning performed without
      contrast. The observation of a decreased renal mass of both kidneys, combined
      with either bumpy contours or papillary calcifications, has been found to have
      high diagnostic specificity and sensitivity. However, the question remains as to
      what kind of analgesics can cause analgesic nephropathy. In the majority of early
      reports about this condition, phenacetin was singled out as the nephrotoxic
      culprit. However, during the last decade the nephrotoxic potential of
      nonphenacetin-containing preparations has become apparent. It is clear that
      people who abuse analgesics prefer combination analgesics containing 2 analgesics
      combined with caffeine and/or codeine. In contrast, abuse of products containing
      only aspirin (acetylsalicylic acid) or paracetamol (acetaminophen) is seldom
      described and associated renal disease is only occasionally reported.
      Experimental evidence of the nephrotoxicity of analgesic preparations is not well
      established. The results of studies involving analgesic administration in animals
      remain contradictory. Clinical evidence linking high consumption of analgesic
      preparations with analgesic nephropathy is overwhelming. Most patients who admit
      to over-consuming analgesics have taken preparation containing more than one
      compound. In recent years, it has become more apparent that preparations not
      containing phenacetin also have the potential to cause nephrotoxicity manifesting
      as identical renal lesions. Further epidemiological evidence of the nephrotoxic
      potential of analgesic combinations has come from case-control studies published
      during the last decade and from 2 prospective cohort studies. Effective
      prevention of analgesic nephropathy consists of the prohibition of over-the
      counter sales of preparation containing at least 2 analgesics associated with
      caffeine and/or codeine.

PMID- 9935275
TI  - Comparative tolerability of erythromycin and newer macrolide antibacterials in
      paediatric patients.
AB  - The macrolides are a well established group of antibacterials frequently used in
      general practice. The most frequently used macrolides in paediatric patients are
      erythromycin, a naturally occurring compound, and clarithromycin and
      azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to
      26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin
      have been described in children. Adverse gastrointestinal effects, including
      nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in
      children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects
      involving the central and peripheral nervous systems have also been observed in
      children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been
      rarely described in children. Treatment-related laboratory abnormalities have
      been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin-
      and azithromycin-treated children. Elevation in liver function tests was the most
      common abnormality cited. Increased macrolide use in children in recent years has
      resulted in a growing potential for drug interactions between them and other
      pharmacologically active agents via the inhibition of cytochrome P450 (CYP)
      microsomal enzymes. Drug interactions with theophylline, cyclosporin,
      carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is
      a weak inducer of CYP and exhibits fewer drug-drug interactions than
      erythromycin. However, its use with theophylline, carbamazepine and terfenadine
      is contraindicated. In contrast, no significant interactions have been reported
      with azithromycin to date. Macrolides have been proven to be well tolerated in
      the treatment of upper and lower respiratory tract infections, skin and soft
      tissue infections, and also in less frequent infections occurring in paediatric
      patients. In addition, clarithromycin and azithromycin have shown good
      tolerability profiles in immunocompromised paediatric patients. In conclusion,
      macrolides antibacterials have proven to be well tolerated in paediatric
      patients. Although the incidence of adverse effects is similar with the use of
      erythromycin and the newer macrolides, drug interactions occur significantly less
      when clarithromycin or azithromycin are administered.

PMID- 9935276
TI  - A risk-benefit assessment of abciximab in angioplasty.
AB  - Advances in percutaneous coronary intervention (PCI) have allowed procedures to
      be performed on a variety of patients with a spectrum of challenging coronary
      anatomy. Abciximab has permitted further expansion and has made the procedure
      safer. Abciximab is a chimerised murine monoclonal antibody directed against the
      platelet glycoprotein (GP) IIb-IIIa receptor. Binding to this receptor inhibits
      platelet aggregation to a wide variety of biological agonists. It also binds to
      alphavbeta3 and leucocyte MAC-1 receptors; the biological significance of its
      affinity to these receptors is unclear. Abciximab has an extremely short plasma
      half-life. Since abciximab binds to the platelet GP IIb-IIIa receptor with great
      avidity it has an extremely long biological half-life. The use of abciximab is
      currently confined primarily to PCIs. The first large trial, EPIC, established
      that abciximab, given with aspirin (acetylsalicylic acid) and heparin, reduced
      the frequency of peri-procedural ischaemic events by 35% in high-risk patients.
      For this reduction a bolus of 0.25 mg/kg was followed by a 12-hour infusion of
      abciximab. However, the transfusion rate was doubled. A subsequent trial, EPILOG,
      indicated that reduction of the dose of heparin along with expeditious removal of
      arterial access sheaths, reduced the rate of haemorrhagic complications to a
      level comparable with placebo-treated patients. while also amplifying the
      reduction in ischaemic events. In a third trial, EPISTENT, this benefit was shown
      to include patients undergoing elective coronary stent implantation. Additional
      trials have demonstrated that the same effect is present in patients undergoing
      primary PCI for acute myocardial infarction and in patients undergoing PCI for
      refractory unstable angina pectoris. In the latter situation, treatment with
      abciximab for 18 to 24 hours preceding the intervention reduced the rate of
      myocardial infarction even before the procedure was begun. The rationale for the
      use abciximab is thus clearly established. Bleeding complications can be reduced
      by limiting the heparin dose, avoiding unneeded venous access site punctures, and
      expeditious removal of arterial sheaths. In emergency coronary artery bypass
      surgery, platelet transfusion reduces the number of receptors occupied per
      platelet and is likely to reduce the degree of postoperative bleeding. The cost
      of abciximab remains an issue; however, this is partially offset by the reduction
      in ischaemic complications and accompanying resource use. In patients undergoing
      elective coronary stenting, abciximab use reduced the long term rate of target
      vessel revascularisation. The degree to which this reduction results in further
      cost savings will require further analysis.

PMID- 9935278
TI  - Inhaled corticosteroids and cataract: prevalence, prevention and management.
AB  - Oral and topical (ocular) corticosteroids are known to have the potential to
      cause cataracts, but inhaled corticosteroids have generally been considered to be
      free of this adverse effect. However, a large epidemiological study has recently
      found a strong association in adults between use of inhaled corticosteroids and
      risk of posterior subcapsular cataract, the most serious type of cataract. This
      is likely to be a causal association as the association was strong (odds ratio of
      10 for heavy users of corticosteroids compared with nonusers); in addition, there
      was a dose-response relationship and the association is biologically plausible.
      For people with asthma, the benefits of inhaled corticosteroids for management of
      their respiratory symptoms will be much greater than the risk of cataract. This
      is particularly true for children, in whom the risk of cataract is extremely low.
      Nevertheless, the existence of serious adverse effects of inhaled corticosteroids
      means they should be used for the shortest duration, and in the lowest dose,
      compatible with effective asthma management.

PMID- 9935280
TI  - European food and nutrition policies in action. Introduction.

PMID- 9935281
TI  - European food and nutrition policies in action. Shaping food and nutrition policy
      in the new Europe.

PMID- 9935282
TI  - European food and nutrition policies in action. Dilemmas and issues for Europe.

PMID- 9935279
TI  - Treatment of cardiac arrhythmias during pregnancy: safety considerations.
AB  - Maternal and fetal arrhythmias occurring during pregnancy may jeopardise the life
      of the mother and the fetus. When arrhythmias are well tolerated and patients are
      minimally symptomatic, conservative therapy, such as observation and rest or
      vagal manoeuvres, should be employed. When arrhythmias cause debilitating
      symptoms or haemodynamic compromise, antiarrhythmic drug therapy is indicated.
      Although no antiarrhythmic drug is completely safe during pregnancy, most are
      well tolerated and can be given with relatively low risk. Physiological changes
      that occur during pregnancy mandate caution when administering antiarrhythmic
      drugs, with close monitoring of serum concentration and patient response. Drug
      therapy should be avoided during the first trimester of pregnancy if possible,
      and drugs with the longest record of safety should be used as first-line therapy.
      Several therapeutic options exist for most arrhythmias in the mother and fetus.
      Of the class IA agents, quinidine has the longest record of safety during
      pregnancy, and is generally well tolerated. Procainamide is also well tolerated,
      and should be a first line option for acute treatment of undiagnosed wide complex
      tachycardia. All IA agents should be administered in the hospital under cardiac
      monitoring due to the potential risk of ventricular arrhythmias (torsade de
      pointes). The IB agent, lidocaine (lignocaine), has local anaesthetic role but is
      also generally well tolerated as an antiarrhythmic agents. Phenytoin should be
      avoided due to the high risk of congenital malformations and limited role as an
      antiarrhythmic drug. Of the IC agents, flecainide has been shown to be very
      effective in treating fetal supraventricular tachycardia complicated by hydrops.
      Beta-Blockers are generally well tolerated and can be used with relative safety
      in pregnancy, although recent data suggest that they may cause intrauterine
      growth retardation if they are administered during the first trimester.
      Amiodarone, a class II agents with characteristics of the other antiarrhythmic
      drug classes, has been reported to cause congenital abnormalities; it should be
      avoided during the first trimester and used only to treat life-threatening
      arrhythmias that fail to respond to other therapies. Adenosine is generally safe
      to use in pregnancy, and is the drug of choice for acute termination of maternal
      supraventricular tachycardia. Digoxin has a long track record of treating both
      maternal and fetal arrhythmias, and is one of the safest antiarrhythmics to use
      during pregnancy. Direct current cardioversion to terminate maternal arrhythmias
      is well tolerated and effective, and should not be delayed if indicated. The use
      of an implantable cardioverter-defibrillator should be considered for women of
      childbearing potential with life-threatening ventricular arrhythmias.

PMID- 9935283
TI  - European food and nutrition policies in action. Cultural modelling: a new basis
      for education of the public.

PMID- 9935277
TI  - A risk-benefit assessment of pharmacotherapies for clinical depression in
      children and adolescents.
AB  - Child and adolescent major depressive disorders are common and recurrent
      disorders. The prevalence of major depressive disorders is estimated to be
      approximately 2% in children and 4 to 8% in adolescents. Major depressive
      disorders in children are frequently accompanied by other psychiatric disorders,
      poor psychosocial outcome and a high risk of suicide and substance abuse,
      indicating the need for effective treatment and prevention. The use of
      antidepressant medications as the first line of treatment for children and
      adolescents with mild to moderate major depressive disorders has been questioned.
      However, some subgroups of patients may benefit from initial treatment with
      antidepressants. These subgroups may include patients who are unwilling or unable
      to undergo psychotherapy, have not responded to at least 8 to 12 sessions of
      psychotherapy, have bipolar, atypical or severe depression or have recurrent
      depression. Currently, the selective serotonin (5-hydroxytryptamine; 5-HT)
      reuptake inhibitors are the first medication choice because of their efficacy,
      benign adverse effect profile, ease of use and low risk of death following an
      overdose. Further research in continuation and maintenance treatments, treatment
      of comorbid conditions, subtypes of depression, e.g. bipolar, atypical, seasonal,
      and combinations of pharmacotherapy and psychotherapy are needed. In addition,
      studies of the pharmacokinetics, pharmacodynamics and long term adverse effects
      of antidepressant medications in children and adolescents are warranted.

PMID- 9935284
TI  - European food and nutrition policies in action. The Maltese food and nutrition
      policy.

PMID- 9935285
TI  - European food and nutrition policies in action. Framework and options for action
      on food and nutrition policies in European countries.

PMID- 9935286
TI  - European food and nutrition policies in action. Nutrition policies or plans of
      action in Europe.

PMID- 9935287
TI  - European food and nutrition policies in action. Food and nutrition policy in this
      century.

PMID- 9935288
TI  - European food and nutrition policies in action. Viewpoints on some major issues.

PMID- 9935289
TI  - European food and nutrition policies in action. Norwegian nutrition policy:
      progress, problems and prospects.

PMID- 9935290
TI  - European food and nutrition policies in action. Finland's food and nutrition
      policy: progress, problems and recommendations.
AB  - Some progress has clearly been made in several aspects of Finland's food and
      nutrition policy: access to nutrition information and education, improvements in
      mass catering, increased availability of healthier food products, and pricing and
      quality requirements favourable to a healthy diet. Finnish eating patterns have
      improved in relation to some recommended foods and macronutrients. The structural
      changes in farm and food production are largely the result of new political and
      economic realities both in Finland and internationally, resulting in the
      Government focusing on fiscal efficiency, decentralization and a more
      competitive, consumer-oriented market. This new environment is creating pressures
      to reduce surplus animal fat production and to expand markets in new foods for
      Finns and other Europeans who, for reasons of demography, health or working or
      living arrangements, demand new and sometimes healthier foods. Within this
      context, some health leaders have been able to make and work for proposals that
      are consistent both with political and economic imperatives and with health
      needs. Although the populations health status is improving and in some respects
      is exemplary, diet-related death and illness rates and risk factors (such as
      serum cholesterol and obesity) are high and their decline, along with some
      healthy changes in eating patterns, has slowed since the mid-1980s (ironically,
      since the adoption of the nutrition policy). The more slowly improvements occur,
      the higher will be the social and economic costs. Major problems in policy
      implementation exist. Although much has been done in research and demonstration
      and in the development of national guidelines (in public catering and labeling,
      for example) there is an apparent lag in translating such soft technology into
      action and monitoring its implementation in order to develop corrective measures
      at the operational level. This problem may increase with decentralized budget
      control and a less regulated market, where listening to the consumer (whether an
      individual, retailer or caterer) may not necessarily result in healthier products
      are more accurate consumer information, especially as foreign products and media
      continue to attract Finnish young people. The lack of a leading strategic body
      that can authoritatively assess and anticipate problems in implementation, deal
      with them and coordinate and monitor the necessary action in fundamental to these
      issues. Rapid progress in economic and farm policy development and food
      enterprises can provide conditions supportive of health and nutrition goals if
      such interests are systematically taken into account and allowed to moderate
      potential negative changes. If it is to be effective, such accounting will
      require initiative, clarity of strategic purpose and organization by health and
      nutrition leaders.

PMID- 9935291
TI  - European food and nutrition policies in action. Denmark's experience with food
      and nutrition policies.

PMID- 9935292
TI  - European food and nutrition policies in action. Icelandic nutrition policy:
      success through compromise.

PMID- 9935293
TI  - European food and nutrition policies in action. Past experiences in nutrition
      policy in eastern countries of the European Region.

PMID- 9935294
TI  - European food and nutrition policies in action. Progress reports.

PMID- 9935295
TI  - [The paradox of tobacco. Smokers have a better post-infarct prognosis].

PMID- 9935296
TI  - [Coronary artery spasm: physiopathology and clinical presentation].

PMID- 9935297
TI  - [A new epileptic syndrome: ring chromosome 20--interhemispheric peak delay of
      spikes].

PMID- 9935298
TI  - [A case of progressive dystonia with serum anti-neuronal antibodies against to
      the basal forebrain cholinergic neurons].

PMID- 9935299
TI  - [Risk factors in evoked neurological disorder by watching an animated program,
      pocket monsters].

PMID- 9935300
TI  - Biological Effects of Light. Basel, Switzerland, November 1-3, 1998. Abstracts.

PMID- 9935301
TI  - Proceedings of the 5th European Symposium on Calcium Binding Proteins in Normal
      and Transformed Cells. Munster/Nordkirchen, Germany, July 30-August 2, 1998.

PMID- 9935302
TI  - Reformulation of thermodynamic systems with aggregation and theoretical methods
      for the analysis of ligand binding in proteins with monomer-multimer equilibria.
AB  - The reformulation of complex thermodynamic systems is a useful tool for their
      analysis as demonstrated by the theoretical analysis of conformationally mediated
      cooperativity in a dimeric protein. Many chemical and biochemical systems exhibit
      monomer-multimer equilibria, behavior not addressed in the original
      reformulation. A method for reformulating such systems, and the mathematical
      methods necessary for relating alternative models, are therefore developed. The
      basic principles of the reformulation are illustrated on homodimeric and
      heterodimeric systems. The mathematical methods necessary to relate alternative
      models are then derived from probabilistic considerations. Higher-order models
      (more interacting subunits) are related to lower-order models (fewer interacting
      subunits) by a polynomial expansion of the sum of species in the lower-order
      model to give the sum of species in the higher-order model. Using these methods,
      the equations describing the ligand binding behavior of a homomeric monomer-dimer
      system are derived. These methods are also used to relate the two alternative
      models for cooperativity for a homotetrameric protein; one model where the dimer
      is the cooperative unit and the other where the tetramer is the cooperative unit.

PMID- 9935303
TI  - Identification of fibronectin IIICS variants in human bone marrow stroma.

PMID- 9935304
TI  - Lingual lesions secondary to prolonged contact with salsalate tablets.

PMID- 9935305
TI  - [1997 Continuing education for physicians and social workers in the public health
      service. Augsburg, 27-29 October 1997. Proceedings].

PMID- 9935306
TI  - Calcium-binding allergens: from plants to man.
AB  - Calcium-binding proteins contain a variable number of motifs, termed EF-hands,
      which consist of two perpendicularly placed alpha-helics and an inter-helical
      loop forming a single calcium-binding site. Due to their ability to bind and
      transport calcium as well as to interact with a variety of ligands in a calcium
      dependent manner, they fulfill important biological functions in eukaryotic
      cells. After parvalbumin, a three EF-hand fish allergen, calcium-binding
      allergens were discovered in pollens of trees. grasses and weeds and, recently,
      as autoallergens in man. Although only a small percentage of atopic individuals
      displays IgE reactivity to calcium-binding allergens, these allergens may be
      important because of their ability to cross-sensitize allergic individuals.
      Confrontation and stability++ as well as IgE recognition of calcium-binding
      allergens greatly depend on the presence of protein-bound calcium ions. It is
      thus likely that hypoallergenic derivatives of calcium-binding allergens can be
      engineered by recombinant DNA technology for immunotherapy++ of sensitized
      patients.

PMID- 9935308
TI  - 5th European Symposium on Platelet and Granulocyte Immunobiology. S'Agaro,
      Girona, Spain. 9-12 May 1998. Abstracts.

PMID- 9935307
TI  - Space Neuroscience Research. Proceedings of a workshop. Paris, France, April 22
      24, 1997.

PMID- 9935309
TI  - Proceedings of the 2nd annual meeting of the Japanese Research Society for
      Helicobacter pylori Related Gastroduodenal Diseases. Kobe, Japan, April 16-17,
      1996.

PMID- 9935310
TI  - Conference report. The Third European Forum on Quality Improvement in Health
      Care.

PMID- 9935312
TI  - Combing the web.

PMID- 9935311
TI  - Chemistry on a pinhead.

PMID- 9935314
TI  - Current awareness in geriatric psychiatry.

PMID- 9935313
TI  - Lipid clinics.

PMID- 9935315
TI  - Incidental liver abnormalities at laparoscopy for benign gynecologic conditions.
AB  - STUDY OBJECTIVE: To evaluate liver abnormalities among women undergoing
      laparoscopy for benign gynecologic conditions. DESIGN: Prospective study
      (Canadian Task Force classification II-2). SETTING: Tertiary care academic
      centers. PATIENTS: Women undergoing laparoscopy for benign gynecologic
      indications. INTERVENTION: The upper abdomen was examined by directing the
      laparoscope cranially. MEASUREMENTS AND MAIN RESULTS: Incidental liver
      abnormalities were found in 4.7% of 823 patients. The most common was perihepatic
      adhesions (Fitz-Hugh-Curtis syndrome), located mainly on the right lobe (66.7%)
      or on both lobes. Pelvic inflammatory disease was present in one-half of women
      with perihepatic adhesions. Other abnormalities were consistent with hepatic
      cirrhosis, adenoma, and hemangioma. CONCLUSION: Our results suggest the
      importance of exploring the upper abdomen during laparoscopic surgery.

PMID- 9935316
TI  - Teloscopy.

PMID- 9935317
TI  - Preventing hyponatremic encephalopathy.

PMID- 9935318
TI  - Focus on: gene therapy in oncology. Introduction.

PMID- 9935319
TI  - UV and the Immune System. Round table summary and general discussion. Paris,
      France, February 6, 1998.

PMID- 9935320
TI  - Guess What! Occupational contact psoriasis.

PMID- 9935321
TI  - Guess What! Kaposi's sarcoma.

PMID- 9935322
TI  - Bleomycin-induced digital gangrene.

PMID- 9935323
TI  - Environmental, occupational health and safety in agriculture: the boundary of two
      millennia. International conference held between 8-11 September 1998 in Kiev,
      Ukraine.

PMID- 9935324
TI  - Quinacrine for treatment of giardiasis.

PMID- 9935325
TI  - Protection of travelers against Hepatitis A viral infection in developing
      countries.

PMID- 9935326
TI  - Practice guidelines for patients with gastrointestinal surgical diseases. The
      Society for Surgery of the Alimentary Tract Patient Care Committee.

PMID- 9935327
TI  - Treatment of gallstone and gallbladder disease using cholecystectomy. The Society
      for Surgery of the Alimentary Tract Patient Care Committee.

PMID- 9935328
TI  - Treatment of acute pancreatitis. The Society for Surgery of the Alimentary Tract
      Patient Care Committee.

PMID- 9935329
TI  - Surgical treatment of chronic pancreatitis. The Society for Surgery of the
      Alimentary Tract Patient Care Committee.

PMID- 9935330
TI  - Importance of preoperative and postoperative pH monitoring in patients with
      esophageal achalasia.

PMID- 9935331
TI  - Esophagectomy volume and operative mortality.

PMID- 9935332
TI  - Alpha-inhibin immunostaining in diagnostic pathology.

PMID- 9935333
TI  - Proceedings of the VIIIth World Congress on Gestational Trophoblastic Diseases.
      Seoul, Korea, November 3-6, 1996.

PMID- 9935334
TI  - Diagnostic yield of push-type enteroscopy in relation to indication.

PMID- 9935335
TI  - Incidence of neoplastic polyps in ileal pouch of patients with familial
      adenomatous polyposis after restorative proctocolectomy.

PMID- 9935336
TI  - Photothermal laser ablation of Barrett's oesophagus: endoscopic and histologic
      evidence of squamous re-epithelialisation.

PMID- 9935337
TI  - [Neurotrophic factor and nerve degenerative diseases].

PMID- 9935338
TI  - Spontaneous clearance of hepatitis B surface antigen in chronic hepatitis B virus
      infection confers a favorable response.

PMID- 9935339
TI  - r-Interferon alfa-2b/ribavirin combined therapy followed by low-dose r-interferon
      alfa-2b in chronic hepatitis C interferon nonresponders.

PMID- 9935340
TI  - Mode of transmission of hepatitis C and clinical outcome correction.

PMID- 9935341
TI  - Immunoglobulin transmits hepatitis C. True or false?

PMID- 9935342
TI  - Missing data in Likert ratings: A comparison of replacement methods.
AB  - The effects of using two methods (item mean and person mean) for replacing
      missing data in Likert scales were studied. The results showed that both methods
      were good representations of the original data when both the number of
      respondents with missing data and the number of items missing were 20% or less.
      As the numbers of missing items and of respondents with missing data increased
      for the person mean substitution method, a spurious increase in the inter-item
      correlations (and, therefore, reliability) for the sale was produced. The item
      mean substitution reduced the reliability estimates of the scale. These results
      suggest caution in the use of the person mean substitution method as the numbers
      of missing items and respondents increase.

PMID- 9935345
TI  - Annual scientific meeting of the British Hypertension Society. 14-16 September
      1998. Abstracts.

PMID- 9935344
TI  - Introduction of Janine N. Caira as the Henry Baldwin Ward Medalist for 1998.

PMID- 9935343
TI  - The Reader's Circle: giving credit where credit is due.

PMID- 9935346
TI  - [Construction of an image transmission system for tele-mentoring during
      endoscopic surgery].

PMID- 9935347
TI  - [Possibility for improving the capability of histological diagnosis of breast
      cancer by employing color Doppler ultrasonography].

PMID- 9935348
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 3-1999. A 41-year-old woman with muscle weakness, painful
      paresthesias, and visual problems.

PMID- 9935349
TI  - Sentinel-lymph-node biopsy.

PMID- 9935350
TI  - Treatment of breast cancer.

PMID- 9935351
TI  - Treatment of breast cancer.

PMID- 9935352
TI  - Antidepressants and falls among nursing home residents.

PMID- 9935353
TI  - Absence of toxicity of avenin in patients with dermatitis herpetiformis.

PMID- 9935354
TI  - Ethical guidelines for physician payment based on capitation.

PMID- 9935355
TI  - Ethical guidelines for physician payment based on capitation.

PMID- 9935356
TI  - Ethical guidelines for physician payment based on capitation.

PMID- 9935357
TI  - Ethical guidelines for physician payment based on capitation.

PMID- 9935358
TI  - Ethical guidelines for physician payment based on capitation.

PMID- 9935360
TI  - Estrogen-dependent tumors. Overview.

PMID- 9935359
TI  - The American health care system--Medicare.

PMID- 9935361
TI  - Proceedings of the 6th Symposium of Human Genetics. Paris, France, 15-16 May
      1998.

PMID- 9935362
TI  - Injection technique. Intravenous--1.

PMID- 9935363
TI  - One blood, two biographies.

PMID- 9935364
TI  - Managed care folly--time to end the silence? .

PMID- 9935366
TI  - Diffuse panbronchiolits.

PMID- 9935367
TI  - [Dissertations defended in 1998].

PMID- 9935365
TI  - Pathologists in the media.

PMID- 9935368
TI  - [The leaders of the Military Medical (Medicosurgical) Academy over the past 200
      years].

PMID- 9935369
TI  - [The Military Medical Academy on memorial medals and phalerae].

PMID- 9935370
TI  - [Military naval therapy: past, present and future (2)].

PMID- 9935371
TI  - [30th Meeting of the German Society of Pediatric Cardiology. Munchen, 10-13
      October 1998. Abstracts].

PMID- 9935372
TI  - [20 Years of balloon dilatation for coronary vessel stenosis. October 18, 1997.
      Proceedings].

PMID- 9935373
TI  - [German Orthopaedic Congress. Wiesbaden, 15-18 October 1998. Abstracts].

PMID- 9935375
TI  - [Teupitzer discussions. 19-20 September 1997].

PMID- 9935374
TI  - [Prevention of Hepatitis B in Switzerland by general vaccination].

PMID- 9935376
TI  - Neurotrauma 1998. European meeting. Magdeburg, 1-3 October 1998. Abstracts.

PMID- 9935377
TI  - Neuromotor Control in Handwriting and Drawing. Proceedings of the 8th
      International Graphonomics Society (IGS) Conference. Genoa, Italy, 24-28 August
      1997.

PMID- 9935378
TI  - Prophylactic extraction of lower third molars: setting the record straight.

PMID- 9935379
TI  - The new Locking Facebow: its use and more.

PMID- 9935380
TI  - Proceedings of the workshop on nutritional support in dialysis with a focus on
      the role of intradialytic parenteral nutrition. December 3, 1997.

PMID- 9935381
TI  - 19th Colloquium of the International Society of Dermatopathology (ISD). Madrid,
      Spain, November 5-7, 1998. Abstracts.

PMID- 9935382
TI  - Risks and Protective Effects of Alcohol on the Individual. Proceedings of a
      conference.

PMID- 9935384
TI  - ACEP business arrangements. American College of Emergency Physicians.

PMID- 9935383
TI  - The next-generation emergency department.

PMID- 9935385
TI  - Proceedings of the 3rd European Workshop on Basic Biology of Head and Neck
      Cancer: Finding Consensus on the Use of Prognostic Factors and Predictive
      Markers. Oslo, Norway, 28-31 August 1997.

PMID- 9935386
TI  - Bullous and hemorrhagic lesions.

PMID- 9935387
TI  - Bullous eruption in a 36-year old man with polycystic kidney disease.

PMID- 9935388
TI  - Tense blisters after bone marrow transplantation.

PMID- 9935389
TI  - Toxic eruption in a woman with chronic arthritis.

PMID- 9935391
TI  - Dependence of EPR in diluted magnetic semiconductors on the host lattice.

PMID- 9935390
TI  - Pursuit of the role of free radicals in stunning.

PMID- 9935392
TI  - Transformation to amorphous state of metals by ion implantation: P in Ni.

PMID- 9935394
TI  - Nuclear-magnetic-resonance study of crystalline tellurium and selenium.

PMID- 9935393
TI  - Positron trapping model including spatial diffusion of the positron.

PMID- 9935395
TI  - Electron hopping in FeOCl intercalation compounds: A Mossbauer relaxation study.

PMID- 9935396
TI  - Formic acid on aluminum oxide: A comparison between inelastic-electron-tunneling
      spectroscopy and high-resolution electron-energy-loss spectroscopy.

PMID- 9935397
TI  - Neutron-inelastic-scattering study of the compound YbCuAl.

PMID- 9935398
TI  - Eu2+-->Mn

PMID- 9935400
TI  - Electronic structure, magnetic properties, and Mossbauer isomer shifts of Fe and
      TiFe alloys.

PMID- 9935399
TI  - Electron channeling radiation from diamond.

PMID- 9935401
TI  - Kinetics of the metastable optically induced ESR in a-Si:H.

PMID- 9935403
TI  - Skewed-field technique in muon-spin rotation: Kubo-Toyabe longitudinal and
      transverse relaxation functions.

PMID- 9935402
TI  - Anomaly of the quadrupole interaction in mixed-valence EuPd2Si2.

PMID- 9935405
TI  - Thermodynamics for many-body systems evolving under a periodic time-dependent
      Hamiltonian: Application to pulsed magnetic resonance.

PMID- 9935404
TI  - Excitation of edge modes in the interaction of electron beams with dielectric
      wedges.

PMID- 9935406
TI  - Electron-spin-resonance experiments and theory of the butatriene-to-acetylene
      transition in short-chain polydiacetylene molecules.

PMID- 9935407
TI  - Nottingham effect of a superconducting metal.

PMID- 9935408
TI  - Dissipative dynamics of a two-state system coupled to a heat bath.

PMID- 9935409
TI  - Diamagnetic susceptibility of superconducting clusters: Spin-glass behavior.

PMID- 9935410
TI  - Superconducting fluctuation conductivity in a magnetic field in two dimensions.

PMID- 9935411
TI  - Vortex-pair state in rotating superfluid 3He-A at low temperatures.

PMID- 9935413
TI  - s-f hybridization model of UBe13.

PMID- 9935412
TI  - Experimental study on the collective theory of flux pinning in a high-field
      superconductor.

PMID- 9935415
TI  - Upper critical field in the superconducting Kondo lattice.

PMID- 9935414
TI  - Symmetry and structure of quantized vortices in superfluid 3He-B.

PMID- 9935416
TI  - Low-temperature heat capacity of electrotransport-purified scandium, yttrium,
      gadolinium, and lutetium.

PMID- 9935418
TI  - Particle-hole symmetry violation in normal liquid 3He.

PMID- 9935417
TI  - Acoustic plasmons in a two-component superconducting Coulomb liquid.

PMID- 9935420
TI  - String melting of the floating phase in antiferromagnetic clock models.

PMID- 9935419
TI  - Critical relaxation of the one-dimensional Blume-Emery-Griffiths model.

PMID- 9935421
TI  - Effective-medium theory of percolation on central-force elastic networks.

PMID- 9935422
TI  - Growth of unstable domains in the two-dimensional Ising model.

PMID- 9935423
TI  - Critical exponents of amorphous Gd0.70Pd0.30.

PMID- 9935424
TI  - Scaling in biased random walks.

PMID- 9935425
TI  - Brillouin scattering study of the ferroelectric phase transition in tris
      sarcosine calcium chloride.

PMID- 9935427
TI  - Kinetics of the order-disorder transition of the two-dimensional anisotropic next
      nearest-neighbor Ising model.

PMID- 9935426
TI  - Localization and absorption of waves in a weakly dissipative disordered medium.

PMID- 9935428
TI  - Successive Ising phase transitions in a random antiferromagnet with competing
      anisotropies.

PMID- 9935429
TI  - Contact propagation: Percolation and other scaling regimes.

PMID- 9935430
TI  - Spin-polarized angle-resolved photoemission study of the electronic structure of
      Fe(100) as a function of temperature.

PMID- 9935431
TI  - Domain-wall renormalization-group study of the three-dimensional random Ising
      model at finite temperature.

PMID- 9935432
TI  - Domain-wall renormalization-group study of the random Heisenberg model.

PMID- 9935433
TI  - Macroscopic renormalization-group study of Anderson localization for
      noninteracting electrons.

PMID- 9935434
TI  - Heat capacity of the commensurate phase and ordering transition of para-H2
      monolayers on graphite.

PMID- 9935435
TI  - Structure factor for dilute magnetic systems.

PMID- 9935437
TI  - Statics and dynamics of spin and electric dipoles in three, four, and other
      dimensions.

PMID- 9935436
TI  - Neutron-diffraction study of the magnetic ordering in Ni(CH2CO2NH2)2

PMID- 9935438
TI  - Helmholtz free energy of an anharmonic crystal to O( lambda 4). III. Equation of
      state for the Lennard-Jones solid.

PMID- 9935439
TI  - Critical exponents for phi3-field models with long-range interactions.

PMID- 9935440
TI  - Kondo-lattice-mixed-valence resistance scaling in heavy-fermion CeCu6 under
      pressure.

PMID- 9935441
TI  - Wetting transitions at solid-gas interfaces.

PMID- 9935442
TI  - Application of parquet perturbation theory to ground states of boson systems.

PMID- 9935443
TI  - Participation ratio in the nonlinear sigma -model representation of localization.

PMID- 9935444
TI  - Dislocation theory of dimer melting in two dimensions: Lipid membranes.

PMID- 9935445
TI  - Influence of nonstoichiometry on the Verwey transition.

PMID- 9935447
TI  - Phase boundaries and critical and tricritical properties of monolayer 4He
      adsorbed on graphite.

PMID- 9935446
TI  - First-order and continuous melting in a two-dimensional system: Monolayer xenon
      on graphite.

PMID- 9935448
TI  - Phase diagrams and magnetic excitations in holmium phosphide.

PMID- 9935450
TI  - Theory of phase transitions from normal to modulated structures in some 1T
      transition-metal dichalcogenides.

PMID- 9935449
TI  - Self-consistent phonons, thermal properties, and vibrational instability of the
      copper crystal.

PMID- 9935451
TI  - Lattice-parameter changes and triclinic distortions in LixMo6Se8 for 0<x<4.

PMID- 9935452
TI  - General theory of spectral diffusion and echo decay in glasses.

PMID- 9935453
TI  - Magnetic properties of the planar antiferromagnet K2FeF4.

PMID- 9935455
TI  - Magnetic dimensionality crossover studies on the Heisenberg antiferromagnet
      Rb2FeCl5

PMID- 9935456
TI  - Discrete theory of kink diffusion in the phi4 lattice with comparison to the
      continuum approximation.

PMID- 9935454
TI  - Magnetic structures in the ternary RM2X2 compounds (R=Gd to Tm; M=Fe, Co, Ni, or
      Cu; X=Si or Ge).

PMID- 9935458
TI  - Muon-spin relaxation in AuFe and CuMn spin glasses.

PMID- 9935457
TI  - Finite temperature excitations of the quantum sine-Gordon-massive Thirring model:
      Variation of the soliton mass with coupling constant and temperature.

PMID- 9935459
TI  - Dynamic cluster-size distribution in cluster-cluster aggregation: Effects of
      cluster diffusivity.

PMID- 9935460
TI  - Light scattering studies of magnon relaxation in NiF2 and FeF2:Mn.

PMID- 9935461
TI  - Ground-state spin pairing of general-spin linear-chain Heisenberg models.

PMID- 9935462
TI  - Magnetism and electron-mass enhancement in zirconium-rich Fe-Zr and Co-Zr
      metallic glasses.

PMID- 9935463
TI  - Persistence up to Ti of ferroelectric-phase-allowed modes in the incommensurate
      phase of K2SeO4.

PMID- 9935465
TI  - High-pressure phase transition in CsBr.

PMID- 9935464
TI  - Localized single-particle excitations for a normal-metal sphere in a
      superconducting host.

PMID- 9935466
TI  - Dynamic random fields in diluted magnetic semiconductors: Cd1-xMnxTe.

PMID- 9935467
TI  - Normal-state properties of heavy-electron systems.

PMID- 9935468
TI  - Magnetic field effects on the soft mode in a singlet ground-state dimer system: A
      neutron scattering study of Cs3Cr2Br9.

PMID- 9935469
TI  - Critical current of thin superconducting wire with side branches.

PMID- 9935470
TI  - Spin canting and reentrance.

PMID- 9935471
TI  - Tc degradation in disordered A15 compounds.

PMID- 9935472
TI  - Analytic approximation for a lattice gas with many interactions.

PMID- 9935473
TI  - Erratum: Two-photon transition from 3H4 to 1S0 of Pr3+ in LaF3

PMID- 9935474
TI  - Energetics of surface roughness and adsorption.

PMID- 9935475
TI  - Monte Carlo study of the equilibration of the random-field Ising model.

PMID- 9935476
TI  - Structure and thermal expansion in solid deuterium.

PMID- 9935477
TI  - Observation of a first-order phase transition in Xe/Ta(110) by photoelectron
      spectroscopy.

PMID- 9935478
TI  - Location of the tricritical point for the melting of commensurate solid krypton
      on ZYX graphite.

PMID- 9935479
TI  - Critical behavior of the three-dimensional Ising spin glass.

PMID- 9935480
TI  - Correlated-cell-model calculation of the high-pressure phase diagram of helium.

PMID- 9935482
TI  - One-magnon Raman scattering in a S=5/2 antiferromagnet.

PMID- 9935481
TI  - Wave-number-dependent susceptibilities of one-dimensional quantum spin models at
      zero temperature.

PMID- 9935483
TI  - Disorder softening of the long-time tail in correlated particle diffusion in one
      dimension.

PMID- 9935485
TI  - Large two-ion magnetoelastic interactions in cubic rare-earth compounds.

PMID- 9935484
TI  - Josephson effect in Lu2Fe3Si5: Evidence against triplet pairing.

PMID- 9935487
TI  - Anomalous ferromagnetism in CeRh3B2: Possibility of a new Kondo-lattice state.

PMID- 9935486
TI  - New class of soliton-supporting polymers: Theoretical predictions.

PMID- 9935488
TI  - Photoemission study of the hydrogenation of the intermetallic compounds YFe3 and
      YFe2.

PMID- 9935490
TI  - Empirical chemical pseudopotential theory of molecular and metallic bonding.

PMID- 9935489
TI  - Quantitative results near the band edges of disordered systems.

PMID- 9935491
TI  - Heterocontact effects in point-contact electron-phonon spectroscopy of the alkali
      metals.

PMID- 9935493
TI  - Surface-sandwich segregation on nondilute bimetallic alloys: Pt50Ni50 and
      Pt78Ni22 probed by low-energy electron diffraction.

PMID- 9935492
TI  - Generalized many-channel conductance formula with application to small rings.

PMID- 9935494
TI  - Resonance scattering of electrons from N2 adsorbed on a metallic surface.

PMID- 9935495
TI  - Spin-polarization instability in a tilted magnetic field of a two-dimensional
      electron gas with filled Landau levels.

PMID- 9935496
TI  - Extended x-ray-absorption fine structure: Direct comparison of absorption and
      electron yield.

PMID- 9935498
TI  - Crystal field of Gd3+ in hexagonal metals.

PMID- 9935497
TI  - Screening of core holes in Al-Mg alloys studied by a comparison of KL1V and
      KL2,3V Auger spectra.

PMID- 9935499
TI  - Theory of the two-peak photoemission spectra in cerium pnictides.

PMID- 9935500
TI  - Supercell calculation of the bremsstrahlung isochromat spectrum of cerium
      phosphide.

PMID- 9935502
TI  - Mechanism for giant enhancements due to defects in low-density-of-states metals.

PMID- 9935501
TI  - Extrema of the density functional for the energy: Excited states from the ground
      state theory.

PMID- 9935503
TI  - Frustration, curvature, and defect lines in metallic glasses and the cholesteric
      blue phase.

PMID- 9935505
TI  - Simple lattice-dynamical slab model for interpreting surface vibrational spectra:
      Application to oxygen on Ni(100) and Ni(111).

PMID- 9935504
TI  - Lattice dynamics of the metastable fcc phase of lanthanum.

PMID- 9935506
TI  - 4f-related electronic structure of gamma -Ce metal.

PMID- 9935507
TI  - Phonon scattering from electrons and low-energy excitations in amorphous Pd-Cu-Si
      containing 3d transition metals.

PMID- 9935508
TI  - Multilayer relaxation for the clean Ni(110) surface.

PMID- 9935509
TI  - Frequency-dependent hopping conductivity in disordered networks in the presence
      of a biased electric field.

PMID- 9935510
TI  - Valence fluctuation and electron spectroscopies in CeN: 4f-ligand versus 4f
      conduction-band hybridization.

PMID- 9935511
TI  - Inverse dielectric function of a periodic-superlattice.

PMID- 9935512
TI  - Plasmon excitation in metallic spheres.

PMID- 9935513
TI  - Size-dependent photoabsorption and photoemission of small metal particles.

PMID- 9935514
TI  - Adsorption of ammonia on the Al(111) surface: Theoretical studies.

PMID- 9935515
TI  - Investigation of the near-surface electronic structure of Cr(001).

PMID- 9935516
TI  - Localization and electron-electron interaction effects in thin Pt wires.

PMID- 9935517
TI  - Characterization of intermixing at metal-semiconductor interfaces by angle
      resolved Auger-electron emission: Cu/Si(111)-7 x 7.

PMID- 9935518
TI  - Decay channels of the 5d-->5f excitation in thorium.

PMID- 9935520
TI  - Solution to the phase problem using x-ray interferometry.

PMID- 9935519
TI  - Electron momentum distribution in Pd and PdH.

PMID- 9935521
TI  - Electronic structure of substitutionally disordered metal alloys: Single-site
      approximation for canonical d bands.

PMID- 9935522
TI  - Analytic investigation of the motion and capture of excitations in fractal
      systems.

PMID- 9935523
TI  - Ion energy distributions from photon- and electron-stimulated desorption:
      Reflection approximation.

PMID- 9935525
TI  - Icosahedral order in glass: Electronic properties.

PMID- 9935524
TI  - In situ investigations of the electronic properties of coevaporated amorphous Mg
      Zn alloy films.

PMID- 9935527
TI  - Conductivity in disordered systems.

PMID- 9935526
TI  - Acceptor-bound phonons in cubic semiconductors.

PMID- 9935528
TI  - Sensitivity of defect energy levels to host band structures and impurity
      potentials in CdTe.

PMID- 9935529
TI  - Binding energies of Wannier excitons in GaAs-Ga1-xAlxAs quantum-well structures
      in a magnetic field.

PMID- 9935530
TI  - Growth, chemical interaction, and Schottky-barrier formation of column-III metal
      overlayers on InP(110).

PMID- 9935531
TI  - Optical and electrical properties of the silver cluster compound (Ag6Ge4P12)Ge6.

PMID- 9935533
TI  - Correlated disorder in two-band models for amorphous semiconductors.

PMID- 9935532
TI  - Anisotropy of the high-energy satellites of the K emission band in graphite.

PMID- 9935534
TI  - Raman scattering intensity of the long-period polytypes of CdI2.

PMID- 9935535
TI  - Total-energy gradients and lattice distortions at point defects in
      semiconductors.

PMID- 9935536
TI  - Localization and energy transfer of quasi-two-dimensional excitons in GaAs-AlAs
      quantum-well heterostructures.

PMID- 9935538
TI  - Spherical model of acceptor-associated bound magnetic polarons.

PMID- 9935537
TI  - Effects of hydrostatic pressure on the low-temperature photoluminescence spectrum
      of heavily doped CdS.

PMID- 9935540
TI  - Cyclotron resonance in the paramagnetic and ferromagnetic phase of a two
      dimensional electron gas with even-integer filling factors.

PMID- 9935539
TI  - Implications of the chiral anomaly for quantum Hall-effect devices.

PMID- 9935541
TI  - Capacitance measurements of a quantized two-dimensional electron gas in the
      regime of the quantum Hall effect.

PMID- 9935543
TI  - Structural quality of Hg1-xCdxTe: Equilibrium point defects.

PMID- 9935542
TI  - Optical absorption and photoluminescence of glow-discharge amorphous Si:F films.

PMID- 9935545
TI  - Exciton-polariton bottleneck and the thermalization of polariton luminescence in
      CdS and CdSe.

PMID- 9935544
TI  - Electron correlations in polyacetylene.

PMID- 9935546
TI  - Ellipsometry and transient reflectivity near the excitonic resonance in CdSe.

PMID- 9935548
TI  - Infrared transmission spectrum of nitrate-intercalated graphite.

PMID- 9935547
TI  - He interaction with Xe and Kr adsorbed on graphite or Ag surfaces.

PMID- 9935550
TI  - Study of the orientation of thiourea adsorbed on aluminum oxide by tunneling
      spectroscopy. II. Comparison of experimental and calculated intensities.

PMID- 9935549
TI  - Study of the orientation of thiourea adsorbed on aluminum oxide by tunneling
      spectroscopy. I. Determination of partial charges from molecular electrostatic
      potential calculations for thiourea and urea.

PMID- 9935551
TI  - Gap-edge states, broken particle-hole symmetry, and kink-antikink asymmetry in
      bounded Peierls systems.

PMID- 9935552
TI  - Structure and dynamics of the H0-tagged Li+ center in KCl as studied by polarized
      Raman scattering.

PMID- 9935553
TI  - Thermodynamic properties of pure and dilute alkali cyanides: Short-range-order
      effects.

PMID- 9935554
TI  - Thermal conductivity and thermopower of graphite at very low temperatures.

PMID- 9935555
TI  - Switendick criterion for stable hydrides.

PMID- 9935556
TI  - Hyper-Raman scattering from alkali halides.

PMID- 9935558
TI  - Fourier-representation method for electronic structure of chainlike systems:
      Restricted Hartree-Fock equations and applications to the (H)x chain in a basis
      of Gaussian functions.

PMID- 9935557
TI  - Angle-resolved photoelectron spectroscopy and band-structure calculations of
      CdI2.

PMID- 9935559
TI  - Relaxation along a single pathway in a quasicontinuum of modes: A trajectory
      treatment of the FA(II) center in KCl:Li.

PMID- 9935560
TI  - Calculations for the transverse N-point phonons in bcc Zr, Nb, and Mo.

PMID- 9935561
TI  - Kohn-Sham exchange potential exact to first order in rho (K

PMID- 9935563
TI  - X-ray observation of a sqrt 3-bar x sqrt 3-bar superlattice in KC8 at high
      pressure.

PMID- 9935562
TI  - Ionization- and cohesive-energy errors arising from norm-conserving
      pseudopotentials.

PMID- 9935564
TI  - Resonance vibrational excitation in electron-energy-loss spectroscopy of adsorbed
      molecules.

PMID- 9935566
TI  - Lattice effect on phase-shift calculations in simple metals.

PMID- 9935565
TI  - Oxygen vacancies in lithium tantalate.

PMID- 9935567
TI  - ac-dc coupling and polarization for charge-density waves in TaS3.

PMID- 9935568
TI  - Electrical conductivity and activation volume for alpha -Li2SO4.

PMID- 9935569
TI  - Enhanced hydrogen solubility in niobium films.

PMID- 9935570
TI  - New results on a two-dimensional electron gas in a tilted magnetic field.

PMID- 9935571
TI  - Approximate determination of Wigner-Seitz radii from free-atom wave functions.

PMID- 9935572
TI  - Thermal conductivity behavior of boron carbides.

PMID- 9935573
TI  - Crystal-induced and image-potential-induced empty surface states on Cu(111) and
      Cu(001).

PMID- 9935574
TI  - Effective elastic constants of superlattices.

PMID- 9935575
TI  - Resonant Raman scattering in mixed GaAs1-xPx crystals.

PMID- 9935576
TI  - Generalized Langevin equation versus the equation-of-motion method for an
      interacting many-electron system.

PMID- 9935577
TI  - Comment on "Monte Carlo calculation of the ground-state energy of an optical
      polaron"

PMID- 9935578
TI  - Reply to "Comment on 'Monte Carlo calculation of the ground-state energy of an
      optical polaron.' "

PMID- 9935579
TI  - Erratum: Effective masses of holes at GaAs-AlGaAs heterojunctions

PMID- 9935580
TI  - Electronic properties of rho (1 x 1) Ni films on Cu(100).

PMID- 9935581
TI  - Final-state effects in the x-ray photoemission spectrum of EuPd2P2.

PMID- 9935583
TI  - Self-consistent calculation of the electron distribution at a jellium surface in
      a strong static electric field.

PMID- 9935582
TI  - Photon-stimulated desorption of H+ ions from OH on Ti and Cr: Comparison with
      bulk solid H2O.

PMID- 9935584
TI  - Experimental symmetry analysis of energy bands near critical points in Pt using
      spin- and momentum-resolved photoemission.

PMID- 9935585
TI  - Anomalous isotope effect for hindered rotations: H2O adsorbed on metal surfaces.

PMID- 9935586
TI  - Statistics of quasi-energy separations in chaotic systems.

PMID- 9935587
TI  - New probe for the ground-state electronic structure of narrow-band and impurity
      systems.

PMID- 9935589
TI  - Hydrogen-acceptor pairs in silicon: Pairing effect on the hydrogen vibrational
      frequency.

PMID- 9935588
TI  - Fractional statistics and fractional quantized Hall effect.

PMID- 9935591
TI  - Effect of temperature gradient on the current oscillations in moving charge
      density waves.

PMID- 9935590
TI  - Resonant interaction of optical phonons with two-dimensional electron and hole
      space-charge layers on silicon.

PMID- 9935592
TI  - Intersubband phonon overlap integrals for AlGaAs/GaAs single-well
      heterostructures.

PMID- 9935593
TI  - Polar heterojunction interfaces: Isovalent interlayers.

PMID- 9935594
TI  - Electric-field-induced macroscopic asymmetry in blue bronze K0.3MoO3.

PMID- 9935596
TI  - X-ray-standing-wave interface studies of germanium on Si(111).

PMID- 9935595
TI  - Exponential band tails in polycrystalline semiconductor films.

PMID- 9935597
TI  - Dense H2 and proton NMR in a-Si:H.

PMID- 9935599
TI  - Optical properties in modulation-doped GaAs-Ga1-xAlxAs quantum wells.

PMID- 9935598
TI  - Evidence of orientation independence of band offset in AlGaAs/GaAs
      heterostructures.

PMID- 9935600
TI  - Pressure dependence of the first-order Raman mode in diamond.

PMID- 9935602
TI  - Local structure of ionic solid solutions: Extended x-ray-absorption fine
      structure study.

PMID- 9935601
TI  - Resistivity study of beta -TbH1.93+x: Observation of an anomaly near 150 K
      similar to that found in alpha -RHx solid solutions.

PMID- 9935604
TI  - Stark-Wannier states in disordered systems.

PMID- 9935603
TI  - Study of Stark-ladder resonances in random chains in a constant electric field.

PMID- 9935605
TI  - Influence of dangling-bond defects on recombination in a-Si:H.

PMID- 9935607
TI  - Sequential two-photon excitation processes of Nd3+ ions in solids.

PMID- 9935606
TI  - Excitation of bubble surface plasmons in rare-gas-irradiated aluminum films.

PMID- 9935608
TI  - Positron-trapping mechanism at grain boundaries.

PMID- 9935609
TI  - Raman heterodyne interference: Observations and analytic theory.

PMID- 9935610
TI  - Raman heterodyne interference: Symmetry analysis.

PMID- 9935611
TI  - Nuclear magnetic resonance and unstable rare-earth magnetism in CeAl3.

PMID- 9935612
TI  - Magnetic and Mossbauer studies on rare-earth-containing Heusler alloys Pd2RSn
      (R=Tb-Yb).

PMID- 9935613
TI  - Correlation effects in ion neutralization scattering with the use of a time
      dependent coupled-cluster approach.

PMID- 9935614
TI  - Tight-binding model for secondary-ion emission.

PMID- 9935615
TI  - High-resolution positron-lifetime study in silver.

PMID- 9935616
TI  - Inelastic scattering time above the superconductivity transition in two
      dimensions: Dependence on disorder and magnetic field.

PMID- 9935617
TI  - Precise determination of h/me using a rotating, superconducting ring.

PMID- 9935618
TI  - Pressure dependence of axisymmetric vortices in superfluid 3He-B.

PMID- 9935619
TI  - Cellular states in a boundary-layer model of directional solidification.

PMID- 9935620
TI  - Condensate fraction and momentum distribution in the ground state of liquid 4He.

PMID- 9935622
TI  - Nonequilibrium quasiparticle distributions from superconducting tunneling
      measurements.

PMID- 9935621
TI  - Structure of elementary excitations and temperature dependence of the momentum
      distribution in liquid 4He.

PMID- 9935624
TI  - Low-temperature magnetization study of U6X (X=Mn,Fe,Co,Ni) compounds.

PMID- 9935623
TI  - Response of type-II superconductors subjected to parallel rotating magnetic
      fields.

PMID- 9935625
TI  - Nonlinear spin dynamics of quantum paramagnetic fluids.

PMID- 9935627
TI  - Frequency-dependent response of an electron on a liquid-helium film.

PMID- 9935626
TI  - Effects of disorder on high-temperature superconductivity in cubic MoN.

PMID- 9935629
TI  - p-wave superconductivity in cubic metals.

PMID- 9935630
TI  - Vortex states in rotating 3He-A in a weak magnetic field.

PMID- 9935628
TI  - Dilatometric measurements of helium densities in bubbles arising from tritium
      decay in tantalum.

PMID- 9935632
TI  - Model for CN- reorientations in the low-temperature phases of KCN and NaCN.

PMID- 9935631
TI  - Fluctuation effects near Hc2 in type-II superconductors.

PMID- 9935633
TI  - Optical absorption, excitation, and emission spectra of Eu3+ in LiNbO3.

PMID- 9935634
TI  - Mean-field theory of magnetic transitions in semi-infinite Ising models.

PMID- 9935636
TI  - Equations of state for classical hard-core systems.

PMID- 9935635
TI  - Smeared antiferromagnetic phase transitions and spin-glass properties in EuxSr1
      xSe.

PMID- 9935637
TI  - Finite-size scaling of two-dimensional axial next-nearest-neighbor Ising models.

PMID- 9935639
TI  - Isotropic spin-1 dipolar and quadrupolar systems: A Green's-function approach.

PMID- 9935638
TI  - Renormalization-group study of the fixed points and of their stability for phase
      transitions with four-component order parameters.

PMID- 9935640
TI  - Anomalous volume expansion in Hg1-xCdxTe melts: An analysis employing the
      inhomogeneous structure model.

PMID- 9935641
TI  - Magnetic properties and short-range order in Co-Nb-B alloys.

PMID- 9935642
TI  - Coupled order parameters in a multisublattice antiferromagnet: Dy3Al5O12 in a
      field along

PMID- 9935644
TI  - Random fields, random anisotropies, nonlinear sigma models, and dimensional
      reduction.

PMID- 9935643
TI  - Experimental evidence for spatial inhomogeneous spin freezing in CuMn.

PMID- 9935645
TI  - First-principles study of structural instabilities in halide-based perovskites:
      Competition between ferroelectricity and ferroelasticity.

PMID- 9935647
TI  - Site dilution, random site exchange, and random-field distribution.

PMID- 9935646
TI  - Sparse-matrix analysis of spin-(1/2) Ising systems.

PMID- 9935649
TI  - N-color spin models in the large-N limit.

PMID- 9935648
TI  - Effective-medium theory of percolation on central-force elastic networks. II.
      Further results.

PMID- 9935650
TI  - Elementary excitations and local spectral distributions in nonhomogeneous
      antiferromagnets.

PMID- 9935651
TI  - Theory of electronic thermal transport: Magnetoquantum corrections to the thermal
      transport coefficients.

PMID- 9935652
TI  - Thermodynamic properties of charge-density waves.

PMID- 9935653
TI  - Premartensitic phases of Ti50Ni47Fe3.

PMID- 9935654
TI  - Monte Carlo simulation of the "Kondo necklace"

PMID- 9935656
TI  - Calculated electronic structure of chromium surfaces and chromium monolayers on
      iron.

PMID- 9935655
TI  - Magnetic ordering processes in the quasi-one-dimensional metamagnets RbFeCl3

PMID- 9935657
TI  - High-pressure phase transitions and equation of state of the III-V compound InAs
      up to 27 GPa.

PMID- 9935659
TI  - Local magnetic field distributions. II. Further results.

PMID- 9935658
TI  - Angle dependence of the field-cooled ESR spectrum of the spin glass CuMn at high
      concentrations: Comparison to hydrodynamic theory.

PMID- 9935661
TI  - Pressure dependence of intramolecular and intermolecular mode frequencies in
      solid oxygen determined by Raman studies.

PMID- 9935660
TI  - New approximation in the Gutzwiller method and its application to the problem of
      itinerant ferromagnetism.

PMID- 9935662
TI  - Dynamic renormalization-group theory of interfaces: Model A.

PMID- 9935664
TI  - Spin waves in lithium at 80 GHz.

PMID- 9935663
TI  - Density of states of the random-hopping model on a Cayley tree.

PMID- 9935665
TI  - Spin waves at surfaces and interfaces in cubic Heisenberg systems.

PMID- 9935666
TI  - Low-temperature resistivity and magnetoresistivity of cerium compounds.

PMID- 9935667
TI  - Temperature dependence of spin dynamics in the impurity-doped one-dimensional
      antiferromagnet (CH3)4NMn2+Cl3:Cd 2+

PMID- 9935668
TI  - Dynamics of the critical wetting transition.

PMID- 9935669
TI  - Preliminary study of the thermal-expansion coefficients of long-range-ordered
      aluminides.

PMID- 9935671
TI  - Localization effects on superconductivity in homogeneous metallic glasses.

PMID- 9935670
TI  - Ground state of the Kondo model.

PMID- 9935673
TI  - Pressure shift of Cr3+-ion-pair emission lines in ruby.

PMID- 9935672
TI  - Relative stability of dense crystalline packings.

PMID- 9935674
TI  - Schottky-type specific heats in liquid Se-Te alloys.

PMID- 9935675
TI  - Short-range ordering in amorphous Fe20Ni60Si10B10.

PMID- 9935676
TI  - ac susceptibility and electrical resistivity in Fe80-xNixCr20 (21 <= x <= 30)
      alloys.

PMID- 9935677
TI  - Equivalence among isotropy subgroups of space groups.

PMID- 9935678
TI  - Erratum: Self-consistent phonons, thermal properties, and vibrational instability
      of the copper crystal

PMID- 9935679
TI  - Coherent phonon scattering and the neutron Kikuchi effect.

PMID- 9935680
TI  - Validity of the (Z+1) ion-core approximation for deep and shallow levels as
      studied by the extended energy-loss fine-structure technique.

PMID- 9935681
TI  - Scaling law for the contact-propagation regime of first-passage percolation.

PMID- 9935683
TI  - Quantum diffusion in dissipative systems.

PMID- 9935682
TI  - Search for magnetic coupling between adsorbed 3He and small copper particles.

PMID- 9935685
TI  - Critical dynamics from statics.

PMID- 9935684
TI  - Possible measurement of the amplitude of a local magnetic moment.

PMID- 9935686
TI  - Spherical spin-glass models with short-range ferromagnetic interaction:
      Thermodynamics and correlation functions.

PMID- 9935687
TI  - Criticality of the D=2 quantum Heisenberg ferromagnet with quenched random
      anisotropy.

PMID- 9935688
TI  - Symmetry and boundary condition of planar spin systems.

PMID- 9935689
TI  - Diffusion on treelike clusters.

PMID- 9935691
TI  - Electron-spin-resonance studies of spin-polarized hydrogen on the surface of
      liquid 4He.

PMID- 9935690
TI  - Magnetic coupling and lattice dynamics in solid O2.

PMID- 9935692
TI  - Calculated inverse photoemission cross sections from adsorbed molecules.

PMID- 9935693
TI  - Model of the local structure of random ternary alloys: Experiment versus theory.

PMID- 9935694
TI  - Image potential for nonplanar metal surfaces.

PMID- 9935695
TI  - Angular distributions of ions desorbing from a stepped surface.

PMID- 9935696
TI  - Electronic structure of AgxPt1-x alloys.

PMID- 9935697
TI  - Relativistic formulation for the nuclear-spin-lattice relaxation rate in metallic
      systems: Applications to AgxPt1-x.

PMID- 9935698
TI  - Surface energy-loss function for the inelastic scattering of electrons from a
      metal substrate with an overlayer of adsorbed alkali-metal atoms.

PMID- 9935699
TI  - Experiments on the high-field thermoelectric and thermal properties of chromium.

PMID- 9935701
TI  - Total-energy local-spin-density approach to structural and electronic properties
      of ferromagnetic iron.

PMID- 9935700
TI  - Total-energy differences: Sources of error in local-density approximations.

PMID- 9935702
TI  - Role of elastic and electronic interactions in trapping of hydrogen by impurities
      in transition metals.

PMID- 9935703
TI  - Fermi surface, effective masses, and Dingle temperatures of ZrTe5 as derived from
      the Shubnikov-de Haas effect.

PMID- 9935704
TI  - Dynamics of bipolarons.

PMID- 9935706
TI  - Incomplete wetting of 4He films on Ag and Au(111) surfaces.

PMID- 9935705
TI  - 1/f noise in a hopping model with trapping.

PMID- 9935707
TI  - Image charge at a metal surface.

PMID- 9935708
TI  - Elastic constants of crystalline sodium from molecular dynamics.

PMID- 9935709
TI  - Analytic methods for the calculation of the electronic structure of solids.

PMID- 9935710
TI  - x dependence of the electronic properties of cubic NaxWO3.

PMID- 9935711
TI  - Surface segregation in jellium binary solid solutions.

PMID- 9935713
TI  - Determination of the conductivity in disordered systems by the potential-well
      analogy.

PMID- 9935712
TI  - Quantum theory of the double layer: A model of the electrode-electrolyte
      interface.

PMID- 9935714
TI  - Magnetoplasma oscillations in a small conducting sphere.

PMID- 9935716
TI  - Comparison of optical reflectivity measurements, electron spectroscopy, and band
      structure calculations of binary transition-metal alloys.

PMID- 9935715
TI  - Optical absorption by a small conducting sphere: Bulk magnetoplasmons.

PMID- 9935718
TI  - Model calculations for the anomalous M4,5VV Auger spectrum for dilute palladium
      in silver.

PMID- 9935717
TI  - Theory of surface electronic states in metallic superlattices.

PMID- 9935719
TI  - Zeeman analysis of the ytterbium luminescence in indium phosphide.

PMID- 9935720
TI  - Phonon dispersion curves of nonstoichiometric Nb3Ge.

PMID- 9935722
TI  - Kinetics of relaxation and recombination of nonequilibrium carriers in GaAs:
      Carrier capture by impurities.

PMID- 9935721
TI  - Dihedral-angle-averaged Bethe lattice for vibrations in glasses.

PMID- 9935723
TI  - Electron correlations in the ground state of covalent semiconductors.

PMID- 9935724
TI  - Hydrogenic impurity states in quantum-well wires: Shape effects.

PMID- 9935725
TI  - Solid-solid phase transitions and soft phonon modes in highly condensed Si.

PMID- 9935727
TI  - Bipolarons in quinolinium di-tetracyanoquinodimethanide

PMID- 9935726
TI  - Gap-state distribution in evaporated a-Si without and with posthydrogenation
      using space-charge-limited-current method.

PMID- 9935728
TI  - Photoluminescence of CdSe: The effect of photoetching.

PMID- 9935729
TI  - Photogenerated solitonic states in trans-polyacetylene.

PMID- 9935730
TI  - Intersubband collective excitations at the surface of a semiconductor
      superlattice.

PMID- 9935732
TI  - Phonon spectra of diamond and zinc-blende semiconductors.

PMID- 9935731
TI  - Photoluminescence quenching in reverse-biased AlxGa1-xAs/GaAs quantum-well
      heterostructures due to carrier tunneling.

PMID- 9935733
TI  - Calculation of the spin-polarized electronic structure of an interstitial iron
      impurity in silicon.

PMID- 9935734
TI  - Electrical and optical properties of FeCl3-doped polyparaphenylene

PMID- 9935735
TI  - Ultrasonic determination of electromechanical coupling and ionization energies in
      Cd1-xMnxTe with 0 <= x <= 0.52 and Cd0.52Zn0.48Te.

PMID- 9935737
TI  - Localization of excitons to Cu-related defects in GaAs.

PMID- 9935736
TI  - Refraction and diffraction of photoelectrons at the Ge(001) surface.

PMID- 9935738
TI  - Effects of higher-J states on nuclear-spin relaxation times for H2 and D2 in
      amorphous silicon.

PMID- 9935739
TI  - Magnetic field and temperature tuning of resonant Raman scattering in diluted
      magnetic semiconductors.

PMID- 9935740
TI  - Electron-impurity tunneling in selectively doped n-type AlxGa1-xAs/GaAs
      heterostructures.

PMID- 9935742
TI  - Optical studies of thermalization mechanisms in a-Si:H.

PMID- 9935741
TI  - Low-temperature thermal conductivity of heavily doped n-type Ge.

PMID- 9935743
TI  - Magneto-optical investigations of phase-transition-induced band-structure changes
      of Pb1-xGexTe.

PMID- 9935745
TI  - g-factor anisotropy of conduction electrons in InSb.

PMID- 9935744
TI  - Metastable-defect behavior in silicon: Charge-state-controlled reorientation of
      iron-aluminum pairs.

PMID- 9935746
TI  - Effect of the magnetic order on the optical-absorption edge in Cd1-xMnxTe.

PMID- 9935748
TI  - High-magnetic-field and high-hydrostatic-pressure investigation of hydrogenic-
      and resonant-impurity states in n-type indium arsenide.

PMID- 9935747
TI  - Fano resonances in chalcogen-doped silicon.

PMID- 9935750
TI  - Frequency-dependent transport in the pure and irradiation-disordered organic
      semiconductor N-methyl-(4-methyl) pyridinium (7,7,8,8-tetracyano-p
      quinodimethanide).

PMID- 9935749
TI  - Role of conduction-electron-local-moment exchange in antiferromagnetic
      semiconductors: Ferrons and bound magnetic polarons.

PMID- 9935751
TI  - Simple calculations of confinement states in a quantum well.

PMID- 9935752
TI  - Experimental band structure of 1T-TiSe2 in the normal and charge-density-wave
      phases.

PMID- 9935753
TI  - Calculations of transfer integrals for tetracyanoquinodimethane salts.

PMID- 9935754
TI  - Synchrotron-radiation study of narrow-band-gap ternary semimagnetic
      semiconductors: Hg1-xMnxSe.

PMID- 9935755
TI  - Ab initio cluster-model study of the on-top chemisorption of F and Cl on Si(111)
      and Ge(111) surfaces.

PMID- 9935756
TI  - k

PMID- 9935757
TI  - Correlated shallow impurity bands in doped semiconductors.

PMID- 9935758
TI  - Arc-evaporated carbon films: Optical properties and electron mean free paths.

PMID- 9935759
TI  - Intensities and asymmetries of electronic Raman scattering in ErPO4 and TmPO4.

PMID- 9935760
TI  - Mechanism of surface dehydration of anatase (TiO2).

PMID- 9935761
TI  - Dipole-dipole interaction effects on the relative stabilities of dipoles in
      NaCl:Mn2+

PMID- 9935762
TI  - Theory of high-field electron transport in silicon dioxide.

PMID- 9935763
TI  - Metal-insulator transition in V4O7: Specific-heat measurements and
      interpretation.

PMID- 9935764
TI  - Laserlike self-excitation of phonons by an inhomogeneously broadened three-level
      system.

PMID- 9935765
TI  - Attenuation of transverse ultrasonic waves near the diffuse solid electrolyte
      transition in CdF2.

PMID- 9935766
TI  - Vibrational thresholds near critical average coordination in alloy network
      glasses.

PMID- 9935767
TI  - Model for F-center production in alkali halides doped with divalent cation
      impurities that change their valence state by irradiation.

PMID- 9935768
TI  - Theory of dephasing relaxation of excitonic polaritons.

PMID- 9935769
TI  - Ultrasonic attenuation in strongly disordered electronic systems.

PMID- 9935772
TI  - X-ray diffuse scattering by cyclohexanol in the plastic phase: A theoretical
      model including orientational and translational molecular correlations.

PMID- 9935770
TI  - Aggregation kinetics of Eu2+-cation vacancy dipoles in the alkali halides: Dimer
      versus trimer formation.

PMID- 9935771
TI  - Effect of composition on charge exchange, lattice expansion, and staging in
      potassium-ammonia graphite intercalation compounds.

PMID- 9935773
TI  - Study of interplanar binding in graphite by extended Thomas-Fermi theory.

PMID- 9935774
TI  - Loosely bound particles in amorphous solids.

PMID- 9935776
TI  - Ab initio calculation of the optical spectra of graphite.

PMID- 9935775
TI  - Crystalline and amorphous FeTi and Fe2Ti.

PMID- 9935777
TI  - Point-contact spectroscopy of copper.

PMID- 9935778
TI  - Satellite structure of the x-ray photoemission in Rb, Ca, and Ba metals.

PMID- 9935779
TI  - Valence charge density in InSb.

PMID- 9935780
TI  - Interlayer interaction in the conduction bands of layered transition-metal
      dichalcogenides studied by inverse photoemission.

PMID- 9935781
TI  - Microstructure and electronic properties of hydrogenated amorphous silicon-carbon
      alloys.

PMID- 9935782
TI  - Metastable state of the 0.68-eV emission in undoped semi-insulating GaAs.

PMID- 9935784
TI  - Small correction to the quantization of Hall conductance due to current-current
      interactions and charge redistribution.

PMID- 9935783
TI  - Interconnection of isothermal elastic data with self-diffusion in sodium.

PMID- 9935786
TI  - Interconnection of activation volumes and activation enthalpies in cubic lead
      fluoride doped with alkali-metal cations.

PMID- 9935785
TI  - Surface correlation energy and the hydrodynamic model of dynamic, nonlocal
      bounded plasma response.

PMID- 9935787
TI  - Homogeneous deformation theory for piezoelectric crystals using the Ewald
      transformation and relationships among electrostatic contributions to second- and
      third-order elastic constants.

PMID- 9935788
TI  - Erratum: Synthesis and peculiar properties of InMo6S8-xSex, T1Mo6S8-x, and
      HgyMo6S8-xSex

PMID- 9935789
TI  - Unoccupied electronic surface states on Cu(110).

PMID- 9935791
TI  - Coulomb correlation in chromium compounds.

PMID- 9935790
TI  - Core-level shifts and the electronic structure of Cu3Au.

PMID- 9935792
TI  - 4f photoemission from Ce clusters and disordered reaction products at Ce/Si and
      Ce/GaAs interfaces.

PMID- 9935794
TI  - Optical investigation of a new type of valence-band configuration in InxGa1-xAs
      GaAs strained superlattices.

PMID- 9935793
TI  - Capacitive noise spectra of a disordered material.

PMID- 9935795
TI  - Shapiro steps in orthorhombic TaS3.

PMID- 9935796
TI  - Long-range order and the fractional quantum Hall effect.

PMID- 9935797
TI  - Interatomic distance and local order in InAs-AlSb semiconductor superlattices.

PMID- 9935798
TI  - Hydrogen-induced change in the 4f localization in CeRu2 studied with x-ray
      photoemission spectroscopy.

PMID- 9935799
TI  - Direct observation of GaP(110) surface states.

PMID- 9935800
TI  - Chemical trends in ground- and excited-state properties of interstitial 3d
      impurities in silicon.

PMID- 9935802
TI  - Low-frequency dielectric response of the charge-density wave in orthorhombic
      TaS3.

PMID- 9935801
TI  - Many-body effects on the luminescence spectrum of modulation-doped quantum wells.

PMID- 9935803
TI  - Shock-front-stimulated optical scattering in water.

PMID- 9935804
TI  - High-pressure Raman study of the optic-phonon modes in BeO.

PMID- 9935805
TI  - Calculation of the 8S7/2 zero-field splitting for Gd3+-doped LaF3.

PMID- 9935806
TI  - Neutron scattering study of the pressure-induced phase transformation in ReO3.

PMID- 9935807
TI  - Experimental equations of state for cesium and lithium metals to 20 kbar and the
      high-pressure behavior of the alkali metals.

PMID- 9935808
TI  - Electron correlation effect in the momentum density of copper metal.

PMID- 9935809
TI  - Simple treatment of the enhancement of Raman scattering due to a two-dimensional
      array of metallic spheroids.

PMID- 9935810
TI  - Bond lengths and coordination numbers from L2,3-edge versus K-edge surface
      extended x-ray-absorption fine structure.

PMID- 9935812
TI  - Energy of immersing a He, Ne, or Ar atom or H2 molecule into a low-density
      electron gas.

PMID- 9935811
TI  - Image potential for stepped and corrugated surfaces.

PMID- 9935813
TI  - Phonon dispersion in the Ta-W system.

PMID- 9935814
TI  - Field dependence of the residual-resistivity anisotropy in sodium and potassium.

PMID- 9935815
TI  - Determining the phase of the structure factor by Kossel cone analysis with the
      use of synchrotron radiation.

PMID- 9935816
TI  - Electronic properties of transition-metal nitrides: The group-V and group-VI
      nitrides VN, NbN, TaN, CrN, MoN, and WN.

PMID- 9935817
TI  - Effects of electron-electron interactions on the valence-band photoemission
      spectra of metals.

PMID- 9935818
TI  - Parametrized version of the generalized pseudopotential theory for noble metals:
      Application to copper.

PMID- 9935819
TI  - Vibronic reduction factors of the excited states in the E <~ Jahn-Teller system.

PMID- 9935820
TI  - Chemical-state studies of Zr and Nb surfaces exposed to hydrogen ions.

PMID- 9935822
TI  - Theory of the scanning tunneling microscope.

PMID- 9935821
TI  - Theory of the direct force in electromigration.

PMID- 9935824
TI  - Effect of an inhomogeneous resistivity on the induced-torque pattern of a metal
      sphere.

PMID- 9935823
TI  - Effect of a magnetic field on the vibrations of an ionic lattice.

PMID- 9935825
TI  - Temperature effects in diffractive atom-surface scattering.

PMID- 9935826
TI  - Oscillatory polarization potential induced at a surface by a penetrating charge.

PMID- 9935827
TI  - Application of intermediate-coupling scheme to the kd6 (k=4,5) system.

PMID- 9935828
TI  - Classical theory for electromagnetic-radiation absorption by a small metallic
      particle.

PMID- 9935829
TI  - Model-potential approach to metal surfaces.

PMID- 9935830
TI  - Electronic densities of states of bimetallic superlattices with interfacial
      diffusion.

PMID- 9935831
TI  - Relativistic and core-relaxation effects on the energy bands of gallium arsenide
      and germanium.

PMID- 9935832
TI  - Effective masses of holes at GaAs-AlGaAs heterojunctions.

PMID- 9935833
TI  - Pulsed ion-beam melting of silicon.

PMID- 9935834
TI  - Commensurate-incommensurate transition in the charge-density-wave state of
      K0.30MoO3.

PMID- 9935835
TI  - Solid H2 in a-Si:H at low temperatures.

PMID- 9935837
TI  - Lattice vibrations in polyacetylene.

PMID- 9935836
TI  - Effect of magnetic field on the energy levels of a hydrogenic impurity center in
      GaAs/Ga1-xAlxAs quantum-well structures.

PMID- 9935838
TI  - Quasiparticle damping in intermediate-valence compounds.

PMID- 9935839
TI  - Far-infrared studies of the phase transition and conduction mechanism in the fast
      ion conductors Ag2HgI4 and Cu2HgI4.

PMID- 9935840
TI  - Photoluminescence determination of the pressure and temperature of the shock wave
      induced by a picosecond laser pulse in the layered semiconductor GaSe.

PMID- 9935841
TI  - Temperature dependence of the dielectric function and the interband critical
      points of InSb.

PMID- 9935842
TI  - Dielectric function of alpha -Sn and its temperature dependence.

PMID- 9935843
TI  - Chemical trends for native defects in III-V-compound semiconductors.

PMID- 9935844
TI  - Surface modes in accumulation layers.

PMID- 9935845
TI  - Universal structural phase transition in network glasses.

PMID- 9935846
TI  - Auger recombination in a quasi-one-dimensional-structure semiconductor.

PMID- 9935847
TI  - Local atomic and electronic arrangements in WxV1-xO2.

PMID- 9935848
TI  - Synthesis and peculiar properties of InMo6S8-xSex, TlMo6S8-xSex, and HgyMo6S8
      xSex.

PMID- 9935849
TI  - Photoemission studies of CuInSe2 and CuGaSe2 and of their interfaces with Si and
      Ge.

PMID- 9935850
TI  - Extended x-ray absorption fine-structure study of hydrogenated amorphous silicon
      germanium alloys.

PMID- 9935851
TI  - Theory of stimulated Raman and Brillouin scattering in noncentrosymmetric
      crystals.

PMID- 9935852
TI  - Simple determination of ac conductivity for multicarrier systems.

PMID- 9935853
TI  - Study of the distribution of localized states in a-Si

PMID- 9935854
TI  - Phase-plot studies of the alternating charge-density-wave current in niobium
      triselenide.

PMID- 9935855
TI  - Heat capacity of antimony pentachloride-intercalated graphite.

PMID- 9935856
TI  - X-ray-absorption spectra in KrF2 and FeCl2: Theory.

PMID- 9935857
TI  - Density-functional theory with self-interaction correction of the electronic
      energy structure of impurity atoms in insulator crystals.

PMID- 9935858
TI  - Low-temperature behavior of potassium and sodium silicate glasses.

PMID- 9935860
TI  - Heat capacity studies on single crystal annealed Fe3O4.

PMID- 9935859
TI  - Low-temperature behavior of vitreous silica containing neon solute.

PMID- 9935861
TI  - Excitation energies of multilevel tunneling states in the presence of large local
      strain fields: A possible model for the glassy state.

PMID- 9935862
TI  - Transition dipole-dipole coupling between the antisymmetric stretching mode of
      azido ligands in K3

PMID- 9935863
TI  - Pressure-dependent conductivity of the molecular conductor Lix{Pt

PMID- 9935864
TI  - H2O-derived contamination of cleaved Si(111)-2 x 1 surfaces.

PMID- 9935865
TI  - Cationic origin of the anomalous resonant photoemission in GaP.

PMID- 9935866
TI  - Unacceptable kinetic energy operators in effective-mass Hamiltonians for graded
      mixed crystals.

PMID- 9935868
TI  - Bond-length relaxation in pseudobinary alloys.

PMID- 9935867
TI  - Possible existence of Lyddane-Sachs-Teller splitting in graphite intercalation
      compounds.

PMID- 9935869
TI  - Local contributions to nonlocal-density potentials.

PMID- 9935870
TI  - Alloy scattering in quantum-well structures of semiconductor ternaries.

PMID- 9935871
TI  - Higher-momentum components of the e+ and e- wave functions in Li and K.

PMID- 9935872
TI  - Volume dependence of the Gruneisen parameter: Alkali metals and NaCl.

PMID- 9935874
TI  - Surface states of clean and metal-overlayer-covered Cr(001) films.

PMID- 9935873
TI  - Erratum: Luminescence processes at chromium in GaAs

PMID- 9935875
TI  - Direct link between 1/f noise and defects in metal films.

PMID- 9935877
TI  - Observation of new surface states on Cu(110) with the use of angle-resolved
      photoelectron spectroscopy.

PMID- 9935876
TI  - Spin-orbit scattering in thin films and on surfaces measured by weak
      localization.

PMID- 9935878
TI  - All-electron local-density determination of the surface energy of transition
      metals: W(001) and V(001).

PMID- 9935879
TI  - Electrical resistivity of dislocations in aluminum.

PMID- 9935880
TI  - Correction to the two-dimensional density of states.

PMID- 9935882
TI  - Transient voltage oscillations in the sliding charge-density-wave state of
      K0.30MoO3.

PMID- 9935881
TI  - Band nonparabolicity effects on weak-coupling polarons in compound
      semiconductors.

PMID- 9935884
TI  - Existence of helical forms of polyacetylene.

PMID- 9935883
TI  - Infrared linewidths and vibrational lifetimes at surfaces: H on Si(100).

PMID- 9935885
TI  - Remarks on fractional statistics.

PMID- 9935886
TI  - Optical spectroscopy of the trivalent silicon defect at the Si-SiO2 interface.

PMID- 9935887
TI  - New Shubnikov-de Haas effects in a two-dimensional electron-hole system.

PMID- 9935889
TI  - Electronic structure of GaAs-Ga1-xAlxAs quantum well and sawtooth superlattices.

PMID- 9935888
TI  - Observation of confined electronic states in GexSi1-xSi strained-layer
      superlattices.

PMID- 9935890
TI  - Investigation of off-center substitutional N in Si.

PMID- 9935891
TI  - Determination of epitaxial overlayer structures from high-energy electron
      scattering and diffraction.

PMID- 9935892
TI  - Interpretation of diffuse low-energy electron diffraction intensities.

PMID- 9935893
TI  - Low-temperature studies of the photoluminescence in CdS under hydrostatic
      pressure.

PMID- 9935894
TI  - Paramagnetic scattering from a cubic ferromagnet Pd2MnSn.

PMID- 9935895
TI  - Magnetic interactions, bonding, and motion of positive muons in magnetite.

PMID- 9935896
TI  - Electron-spin-resonance analysis of the deep donors lead, tin, and germanium in
      CdTe.

PMID- 9935897
TI  - Dielectric properties of ZrN, NbC, and NbN as determined by electron-energy-loss
      spectroscopy.

PMID- 9935898
TI  - High-pressure EPR study of the calcite-CaCO3(II) displacive phase transformation
      near 1.6 GPa.

PMID- 9935900
TI  - Unitary-group approach to the theory of nuclear magnetic resonance of higher-spin
      nuclei. III.

PMID- 9935899
TI  - Unitary-group approach to the theory of nuclear magnetic resonance of higher-spin
      nuclei. II.

PMID- 9935901
TI  - Structural study of GaSb/AlSb strained-layer superlattice.

PMID- 9935903
TI  - Positron-lifetime study of secondary-defect formation in quenched aluminum.

PMID- 9935902
TI  - Time evolution of the structure function of quenched Al-Zn and Al-Zn-Mg alloys.

PMID- 9935904
TI  - General behavior of completely anisotropic ESR hyperfine centers under slow
      orientational diffusion motion.

PMID- 9935905
TI  - Eilenberger equations for moderately dirty superconductors.

PMID- 9935906
TI  - Structure and depolarization properties in the Raman spectra of superfluid 4He.

PMID- 9935908
TI  - Spatial development of multiple-gap states in nonequilibrium superconductors.

PMID- 9935907
TI  - Superconductivity in uranium compounds with Cu3Au structure.

PMID- 9935909
TI  - Theory of a dilute 3He-4He adsorbed film.

PMID- 9935910
TI  - Atomic and molecular hydrogen isotopes in liquid helium.

PMID- 9935911
TI  - Roton-phonon mixing in solid hydrogen and deuterium.

PMID- 9935912
TI  - Studies of return maps, chaos, and phase-locked states in a current-driven
      Josephson-junction simulator.

PMID- 9935913
TI  - Nuclear magnetic resonance in two-dimensional superfluid 3He.

PMID- 9935915
TI  - Sliding charge-density waves as a dynamic critical phenomenon.

PMID- 9935914
TI  - Energy spectrum for a fractal lattice in a magnetic field.

PMID- 9935916
TI  - Screening effects in modulation-doped quantum wells.

PMID- 9935917
TI  - Absolute minimum of Landau's thermodynamic potential.

PMID- 9935918
TI  - Critical quasielastic light scattering in KTa0.968Nb0.032O3.

PMID- 9935919
TI  - Monte Carlo renormalization group for quantum systems.

PMID- 9935920
TI  - Shock temperatures and melting in CsI.

PMID- 9935921
TI  - Structure of dense shock-melted alkali halides: Evidence for a continuous
      pressure-induced structural transition in the melt.

PMID- 9935923
TI  - Order-parameter profile at long distances in an adsorbed binary liquid mixture
      near criticality.

PMID- 9935922
TI  - Magnetic properties of boron-doped silicon.

PMID- 9935925
TI  - Magnetic and vibrational excitations in rare-earth orthoferrites: A Raman
      scattering study.

PMID- 9935924
TI  - Off-axis correlation functions in the isotropic d=2 Ising model.

PMID- 9935926
TI  - Finite-size tests of hyperscaling.

PMID- 9935927
TI  - Green's-function theory of quadrupolar coupled systems.

PMID- 9935928
TI  - Effect of altered surface substrate chemistry on critical adsorption from a
      binary liquid mixture.

PMID- 9935930
TI  - New phases, commensurate-incommensurate and disordering transitions in a solvable
      model of adsorbed layers.

PMID- 9935929
TI  - Electronic structure and magnetic and hyperfine properties of dilute alloys of Fe
      in Ti and Zr hosts.

PMID- 9935931
TI  - Threshold of Barkhausen emission and onset of hysteresis in iron.

PMID- 9935932
TI  - Irrelevant variables, Landau expansions, and cubic anisotropy.

PMID- 9935933
TI  - Time-dependent correlations for axially symmetric infinite-range spin
      Hamiltonians.

PMID- 9935935
TI  - Phase diagrams of the corner cubic Heisenberg model and its site-diluted version
      on a triangular lattice: Renormalization-group treatment.

PMID- 9935934
TI  - Critical dynamics and renormalization-group methods for the kinetic Ising model.

PMID- 9935937
TI  - Ground state of the one-dimensional antiferromagnetic Heisenberg model.

PMID- 9935936
TI  - Growth of order in order-disorder transitions: Tests of universality.

PMID- 9935938
TI  - Absence of excited molecules in sputtering processes.

PMID- 9935939
TI  - Temperature dependence of the excitation energy spectrum of He II.

PMID- 9935940
TI  - Electron nuclear double resonance spectra of cis-rich and trans-rich
      polyacetylenes between 1.9 and 4.2 K.

PMID- 9935941
TI  - Raman-Nath equation and classical diffusion on one-dimensional random chains.

PMID- 9935942
TI  - Equivalence of different definitions of the surface tension.

PMID- 9935943
TI  - Scaling theory of desorption from molecular-sieve materials.

PMID- 9935944
TI  - Structure factors for a binary mixture of quantum and classical fermion liquids.

PMID- 9935945
TI  - Isobaric thermal expansivity of liquids.

PMID- 9935946
TI  - Statistical mechanics of the classical easy-plane Dzialoshinski-Moriya chain in
      an external field.

PMID- 9935947
TI  - Effects of anisotropic surface tension on first-order-transition singularities.

PMID- 9935948
TI  - Properties of spin-aligned deuterium, D

PMID- 9935949
TI  - Magnetic double transition in Au-Fe: Observation of spin canting in zero magnetic
      field.

PMID- 9935951
TI  - Erratum: Generalized Ornstein-Zernike equation

PMID- 9935950
TI  - Channeling radiation from relativistic electrons and positrons.

PMID- 9935952
TI  - Nuclear-magnetic-resonance study of electronic structure in the copper-niobium
      superlattice.

PMID- 9935954
TI  - Mossbauer-effect study of the reentrant transition in Cr75Fe25 alloy.

PMID- 9935953
TI  - Stress-induced site change of H in V observed by channeling experiments.

PMID- 9935955
TI  - Weak-localization, near-magnetism, and triplet-pairing superconductivity in three
      dimensions.

PMID- 9935956
TI  - Phase transition in the superconducting state of U1-xThxBe13 (x=0-0.06).

PMID- 9935957
TI  - Effect of pressure on spin fluctuations and superconductivity in heavy-fermion
      UPt3.

PMID- 9935958
TI  - Distinct modes in the first zero-field current step of Josephson tunnel
      junctions.

PMID- 9935959
TI  - Damping of second sound in superfluid helium by order-parameter relaxation.

PMID- 9935960
TI  - Krypton on graphite and the striped helical Potts model.

PMID- 9935962
TI  - Position-space renormalization for elastic percolation networks with bond-bending
      forces.

PMID- 9935961
TI  - Localization and electron-interaction effects in metallic glasses.

PMID- 9935963
TI  - Possibility of ferroelastic domains in orientational glass state in (KBr)1
      x(KCN)x.

PMID- 9935964
TI  - Fractal chemical kinetics: Binary steady-state reaction on a percolating cluster.

PMID- 9935965
TI  - Percolation-localization crossover and depression of the superconducting
      transition temperature in films of metal-insulator mixtures.

PMID- 9935967
TI  - Theory of phase equilibria in Co-Fe alloys.

PMID- 9935966
TI  - Irreversibility in random-field ferromagnets and diluted antiferromagnets.

PMID- 9935968
TI  - Dynamical behavior of fractal structures.

PMID- 9935969
TI  - Coulomb-gas scaling, superfluid films, and the XY model.

PMID- 9935970
TI  - Elastic moduli near percolation: Universal ratio and critical exponent.

PMID- 9935971
TI  - Ferromagnetic instability of 3He layers adsorbed on Grafoil.

PMID- 9935972
TI  - Localization and quantum-mechanical resonant tunneling in the presence of a time
      dependent potential.

PMID- 9935974
TI  - CO core-excited states for CO/Cu(100): A cluster-model study.

PMID- 9935975
TI  - Electronic structure and scattering in PdBx from de Haas-van Alphen measurements.

PMID- 9935973
TI  - Theory of cyclic-matrix functions with application to the analytic resolution of
      linear combination of atomic orbitals problems.

PMID- 9935976
TI  - Hartree-Fock studies of helium-surface interaction potentials.

PMID- 9935977
TI  - Fermi surface of Pd and Pt under homogeneous strain.

PMID- 9935978
TI  - Valence-band resonance in photoemission from Ni(001) and its relation to the 6-eV
      satellite.

PMID- 9935979
TI  - Competitive irreversible random one-, two-, three-,. point adsorption on two
      dimensional lattices.

PMID- 9935980
TI  - Simplified method for calculating the energy of weakly interacting fragments.

PMID- 9935982
TI  - High-resolution angle-resolved photoemission studies of the surface states on
      Al(111) and Al(001).

PMID- 9935981
TI  - Ion-track model for fast-ion-induced desorption of molecules.

PMID- 9935983
TI  - Electronic structure of small clusters of nickel and iron.

PMID- 9935984
TI  - Electronic and structural properties of sodium clusters.

PMID- 9935985
TI  - Cohesive properties of bcc and fcc rubidium from ab initio pseudopotentials.

PMID- 9935986
TI  - Symmetry properties, normal modes, and free energy of orientationally disordered
      crystals.

PMID- 9935987
TI  - Path-integral method for soliton-bearing systems. II. phi4 and sine-Gordon
      theories in the classical limit.

PMID- 9935988
TI  - Theory of lattice-dynamical properties of compressed solids.

PMID- 9935989
TI  - Determination of the frequency-dependent resistivity of ultrathin metallic films
      on Si(111).

PMID- 9935990
TI  - Electron-hole pair production at metal surfaces.

PMID- 9935991
TI  - Effects of annealing on the attenuated-total-reflection spectra of cold
      evaporated silver films.

PMID- 9935992
TI  - Inelastic scattering of x rays by surface plasmons.

PMID- 9935993
TI  - L-edge x-ray-absorption systematics of the noble metals Rh, Pd, and Ag and the
      main-group metals In and Sn: A study of the unoccupied density of states in 4d
      elements.

PMID- 9935994
TI  - L-edge x-ray-absorption spectra of PdAl3 and PdCl2: A study of charge
      redistribution in compounds of an element with a nearly full 4d shell.

PMID- 9935995
TI  - Crystal structure from one-electron theory.

PMID- 9935996
TI  - Charged vortex excitations in quantum Hall systems.

PMID- 9935997
TI  - Multilayer relaxation of the Fe{210} surface.

PMID- 9935999
TI  - More than one monolayer adsorption of oxygen on the W(112) surface.

PMID- 9935998
TI  - Electronic structure of Mn impurities in noble metals.

PMID- 9936000
TI  - Local order and structural transitions in amorphous metal-metalloid alloys.

PMID- 9936001
TI  - Electronic structure of delta -plutonium and of single Al, Ga, and Sc impurities
      in delta -plutonium.

PMID- 9936002
TI  - Electronic structure of Pu-rich PuxAl1-x alloys.

PMID- 9936003
TI  - Electronic structure of MnSb.

PMID- 9936004
TI  - Angle-resolved photoemission studies of the valence-band structure of stepped
      crystal surfaces: Cu(S)-

PMID- 9936005
TI  - New approach to minimal basis set with localized orbitals: Basic aspects and
      simple examples.

PMID- 9936007
TI  - Experimental study of the 3p-3d intershell interaction in Ca, Sc, Ti, V, and Cr
      metals.

PMID- 9936006
TI  - Investigation of the Hall effect in impurity-hopping conduction.

PMID- 9936009
TI  - Electrical and galvanomagnetic properties of Fe100-xBx metallic glasses (13 <= x
      <= 26).

PMID- 9936008
TI  - Surface electromagnetic modes in metal spheres.

PMID- 9936010
TI  - Magnetoreflectivity study of the band structure of Hg1-xMnxTe (0.026 <= x <=
      0.106).

PMID- 9936011
TI  - Self-consistent semirelativistic energy bands of WSi2.

PMID- 9936012
TI  - Band mixing in semiconductor superlattices.

PMID- 9936013
TI  - Interband optical transitions in GaAs-Ga1-xAlxAs and InAs-GaSb superlattices.

PMID- 9936014
TI  - Folded acoustic and quantized optic phonons in (GaAl)As superlattices.

PMID- 9936015
TI  - Excitonic effect in the optical spectrum of semiconductors.

PMID- 9936016
TI  - Model for the generation of positive charge at the Si-SiO2 interface based on hot
      hole injection from the anode.

PMID- 9936017
TI  - Effects of polysilane formation on the optical and electrical properties of
      binary Si:H alloys.

PMID- 9936019
TI  - Conductivity (ac and dc) in III-V amorphous semiconductors and chalcogenide
      glasses.

PMID- 9936018
TI  - Coulomb interactions in semiconductors and insulators.

PMID- 9936020
TI  - Statistics of solitons in quarter-filled-band, large-U quasi-one-dimensional
      crystals.

PMID- 9936021
TI  - Microscopic effects at GaAs/Ge(100) molecular-beam-epitaxy interfaces:
      Synchrotron-radiation photoemission study.

PMID- 9936022
TI  - Low-temperature heat transport by charge carriers in doped semiconductors.

PMID- 9936023
TI  - Temperature dependence of band gaps in Si and Ge.

PMID- 9936024
TI  - Band structures of all polycrystalline forms of silicon dioxide.

PMID- 9936025
TI  - Ellipsometric study of interband transitions in orthorhombic GeS.

PMID- 9936026
TI  - Chemical bonding of hydrogen and oxygen in glow-discharge-deposited thin films of
      a-Ge:H and a-Ge:(H,O).

PMID- 9936027
TI  - Structural, electrical, and optical properties of a-Si1-xGex:H and an inferred
      electronic band structure.

PMID- 9936028
TI  - Sb overlayers on (110) surfaces of III-V semiconductors: Total-energy
      minimization and surface electronic structure.

PMID- 9936029
TI  - Vibrational and electronic properties of MP15 polyphosphides: Crystalline RbP15,
      KP15, and NaP15.

PMID- 9936031
TI  - Surface dipole and Fermi-level position on clean, oxygen-, and water-covered
      cylindrical Si crystals: A photoelectron spectroscopy study.

PMID- 9936030
TI  - Vibrational and electronic properties of MP15 polyphosphides: KP15 thin films.

PMID- 9936032
TI  - Non-Gaussian effects in 1/f noise in small silicon-on-sapphire resistors.

PMID- 9936033
TI  - Effects of dopants and defects on light-induced metastable states in a-Si:H.

PMID- 9936034
TI  - Domain motion and threshold behavior of charge-density waves.

PMID- 9936036
TI  - Thin-film quantization studies of grey tin epitaxially grown on CdTe(111).

PMID- 9936035
TI  - Electron-hole pair excitation in semiconductors via energy transfer from an
      external sensitizer.

PMID- 9936037
TI  - Position-dependent effective masses in semiconductor theory. II.

PMID- 9936038
TI  - Bonding study of TiC and TiN. I. High-precision x-ray-diffraction determination
      of the valence-electron density distribution, Debye-Waller temperature factors,
      and atomic static displacements in TiC0.94 and TiN0.99.

PMID- 9936039
TI  - Bonding study of TiC and TiN. II. Theory.

PMID- 9936040
TI  - Saturation photoconductivity in CdIn2S4.

PMID- 9936041
TI  - Structure of Sn/Ge(111) from low-energy electron-diffraction and photoemission
      studies.

PMID- 9936042
TI  - Molecular structure of "trans"-polyacetylene: The presence of remnant cis units
      and their influence on soliton formation and diffusion.

PMID- 9936043
TI  - Combined use of ion backscattering and x-ray rocking curves in the analyses of
      superlattices.

PMID- 9936044
TI  - Shallow-impurity states in semiconductor quantum-well structures.

PMID- 9936046
TI  - Picosecond spectroscopy of highly excited CdS.

PMID- 9936045
TI  - Ionized-impurity scattering in the weak-screening limit.

PMID- 9936047
TI  - TiC(001) surface: All-electron local-density-functional study.

PMID- 9936049
TI  - Acceptor-bound magnetic polaron in Cd1-xMnxTe semimagnetic semiconductors.

PMID- 9936048
TI  - Investigation of band masses and g values of ZnSe by two-photon
      magnetoabsorption.

PMID- 9936050
TI  - Native defects in undoped semi-insulating CdSe studied by photoluminescence and
      absorption.

PMID- 9936051
TI  - Exchange energy and oscillator strengths of excitons in cadmium sulfide.

PMID- 9936052
TI  - Electronic and transport properties of hydrogenated amorphous silicon.

PMID- 9936054
TI  - Luminescence and photoconductivity in magnesium aluminum spinel.

PMID- 9936053
TI  - Conductivity studies for an electron surface layer on Hg1-xCdxTe.

PMID- 9936055
TI  - Mie resonance for spherical metal particles in an anisotropic dielectric.

PMID- 9936056
TI  - Coherence in singlet-exciton motion in anthracene crystals.

PMID- 9936057
TI  - Anderson localization in topologically disordered systems.

PMID- 9936058
TI  - Raman microprobe observation of intercalate contraction in graphite intercalation
      compounds.

PMID- 9936059
TI  - Brillouin scattering in molten and crystalline alkali halides.

PMID- 9936060
TI  - Coherent-potential approximation and renormalization-group methods for disordered
      chains.

PMID- 9936062
TI  - Onset of hopping conduction in carbon-ion-implanted diamond.

PMID- 9936061
TI  - Resonant photoemission processes at the 3d edge in UO2(111).

PMID- 9936064
TI  - Total-energy calculations for N2 dissociation on Fe(111): Characterization of
      precursor and dissociative states.

PMID- 9936063
TI  - Exact solution of the stochastic Liouville equation and application to an
      evaluation of the neutron scattering function.

PMID- 9936065
TI  - Ellipsometric investigation of metal-alkali-halide interfaces.

PMID- 9936066
TI  - Electric-field-induced new features in the photoconductivity of extrinsic
      silicon.

PMID- 9936067
TI  - Effect of temperature on exciton trapping on interface defects in GaAs quantum
      wells.

PMID- 9936068
TI  - Pressure dependence of the room-temperature resistance of Co100-xZrx and Fe100
      xZrx glasses.

PMID- 9936069
TI  - Frequency-dependent conductivity of cis-polyacetylene.

PMID- 9936070
TI  - Self-consistent treatment of short-range order in substitutionally disordered
      alloys.

PMID- 9936072
TI  - Symmetry and the reflectivity of diffraction gratings at normal incidence.

PMID- 9936071
TI  - Temperature dependence of transverse acoustic phonons in semiconductors.

PMID- 9936073
TI  - Kramer's equation for physisorption.

PMID- 9936074
TI  - Electronic structure of Si and Ge (111) surfaces and of the Si-Ge(111) interface.

PMID- 9936075
TI  - Magnetic moments and coordination symmetry in bcc Fe-M alloys.

PMID- 9936076
TI  - Electron mobility of Al0.48In0.52As.

PMID- 9936077
TI  - Comment on "Theory of semiconductor heterojunctions: The role of quantum dipoles"

PMID- 9936078
TI  - Erratum: Defect recovery and trapping in plastically deformed Au studied by
      perturbed angular correlations of 111In

PMID- 9936079
TI  - Periodic Laughlin-Jastrow wave functions for the fractional quantized Hall
      effect.

PMID- 9936080
TI  - Structure of c(2 x 2) oxygen on Cu(100): A surface extended x-ray absorption fine
      structure study.

PMID- 9936081
TI  - Magnetic-field-enhanced electron-electron scattering in the resistivity of
      copper.

PMID- 9936082
TI  - Polarizability of alkali clusters.

PMID- 9936084
TI  - Symmetry and orientation of CH3O on Cu(100).

PMID- 9936083
TI  - Core-level shifts for Au epitaxial overlayers on Ag.

PMID- 9936085
TI  - Coupled surface plasmons excited by photons in a free-standing thin silver film.

PMID- 9936086
TI  - He scattering study of the nucleation and growth of Cu(100) from its vapor.

PMID- 9936087
TI  - Photoemission and theoretical studies of GaAs(111) and (1-bar 1-bar 1-bar)
      surfaces: Vacancy models.

PMID- 9936089
TI  - Atomic structure and ordering in semiconductor alloys.

PMID- 9936088
TI  - Effects of quasi-interface states in HgTe-CdTe superlattices.

PMID- 9936090
TI  - Scaling approach to phonon-fracton crossover.

PMID- 9936091
TI  - Radiative recombination in inhomogeneous semiconductors.

PMID- 9936092
TI  - Electronic structure of filled tetrahedral semiconductors.

PMID- 9936093
TI  - Spontaneous decay rates of LA phonons in quasi-isotropic solids.

PMID- 9936094
TI  - Dispersion of collective intersubband excitations in semiconductor superlattices.

PMID- 9936095
TI  - Similarity of Si(110)5 x 1 and Si(111)2 x 1 surfaces.

PMID- 9936096
TI  - Contribution of light holes to thermionic field emission in Si and Ge.

PMID- 9936097
TI  - Electroreflectance study of linear electro-optic effect in the organic solid 2
      methyl-4-nitroaniline.

PMID- 9936098
TI  - Ultrasonic attenuation measurements on crystals which display persistent
      nonphotochemical ir spectral hole burning.

PMID- 9936099
TI  - Spontaneous decay of TA phonons.

PMID- 9936100
TI  - Electric-field-induced first-order Raman scattering in pure KCl and KBr.

PMID- 9936101
TI  - Voltage-dependent scanning-tunneling microscopy of a crystal surface: Graphite.

PMID- 9936102
TI  - Relevance of domain-wall softness for a universal classification of domain-growth
      kinetics.

PMID- 9936103
TI  - Interplay of anisotropy and energy dependence in electron density of states in
      strong-coupling superconductors.

PMID- 9936104
TI  - Nuclear-magnetic-resonance studies and molecular-dynamics simulations of the
      structure of sodium fluoroberyllate glasses: Evidence of non-tetrahedrally
      coordinated beryllium.

PMID- 9936105
TI  - K-shell photoexcitation of solid N2, CO, NO, O2, and N2O.

PMID- 9936107
TI  - Charged-particle excitation of ripplon fields.

PMID- 9936106
TI  - Molecular-dynamics study of atomic motions in water.

PMID- 9936108
TI  - Nuclear-magnetic-resonance study and simulation of the spin configuration in In-
      and Ga-substituted CdCr2S4.

PMID- 9936109
TI  - Magnetic-dipole and electric-quadrupole effects in LaCl3:Tb3+

PMID- 9936110
TI  - Chaos, noise, and tails on the I-V curve steps of rf-driven Josephson junctions.

PMID- 9936112
TI  - Critical currents of cross-type superconducting-normal-superconducting junctions
      in perpendicular magnetic fields.

PMID- 9936111
TI  - 3He melting-curve thermometry at millikelvin temperatures.

PMID- 9936114
TI  - Thermal expansion and the cubic-to-tetragonal transformation in V3Si.

PMID- 9936113
TI  - Effects of energy dependence in the electronic density of states on the far
      infrared absorption in superconductors.

PMID- 9936115
TI  - Degradation of superconductivity in A15 V3Si by explosive compression.

PMID- 9936117
TI  - Damping in coupled, layered helium films.

PMID- 9936116
TI  - Tomasch oscillations in multilayered superconducting systems.

PMID- 9936118
TI  - Phase transition of two-dimensional 3He from a dilute to a dense phase.

PMID- 9936119
TI  - Energy-gap enhancement in superconducting tin by microwaves.

PMID- 9936121
TI  - Fermi-liquid theory for very dirty metals.

PMID- 9936120
TI  - Possibility of superconductivity in the electron-hole liquid.

PMID- 9936122
TI  - Josephson junction at the onset of chaos: A complete devil's staircase.

PMID- 9936123
TI  - Exchange enhancement of the Pauli spin susceptibility in highly disordered
      metals: Superconductivity of Pd.

PMID- 9936124
TI  - Important modifications near a magnetic instability in the particle-hole
      propagator of weakly localized two-dimensional fermion systems.

PMID- 9936125
TI  - Electron-phonon interaction in charge-density-wave superconductors.

PMID- 9936126
TI  - Spin-orbit relaxation and the Knight shift in small superconducting particles of
      simple polyvalent metals.

PMID- 9936128
TI  - Dynamic structure factor for the electron gas in metallic systems.

PMID- 9936127
TI  - Conserving dynamic theory for the electron gas.

PMID- 9936129
TI  - Geometrical resonances in a high-injection-current nonequilibrium state of
      superconductor-normal-metal contacts.

PMID- 9936130
TI  - Fluctuation theory of the specific heat of normal liquid 3He.

PMID- 9936131
TI  - Thermal conductivity and charge imbalance in superconductors.

PMID- 9936133
TI  - Generalized Curie-Weiss law.

PMID- 9936132
TI  - Mixed-valence impurities in a superconducting matrix: 1/Nf expansion.

PMID- 9936134
TI  - gamma -ray-diffraction study of an incommensurate phase: Application to quartz.

PMID- 9936135
TI  - Collective excitations and retarded interactions.

PMID- 9936136
TI  - Equation-of-motion treatment of the N-fold-degenerate Anderson model in the large
      N limit.

PMID- 9936137
TI  - Self-consistent electronic-band-structure calculation for Hg3AsF6.

PMID- 9936138
TI  - Numerical results for the random-field Ising model and the dilute
      antiferromagnetic Ising model in a uniform field.

PMID- 9936139
TI  - Magnetic excitations in chromium. II.

PMID- 9936140
TI  - Critical properties of pure and randomly dilute dysprosium aluminum garnet.

PMID- 9936142
TI  - Random-field critical behavior and the Ginzburg criterion.

PMID- 9936143
TI  - Specific heat of EuxSr1-xS in high magnetic fields.

PMID- 9936141
TI  - Practical algorithm for identifying subgroups of space groups.

PMID- 9936144
TI  - Equivalence of ion-size effect and hydrostatic-pressure effect on exchange
      coupling in spinels and garnets.

PMID- 9936145
TI  - Susceptibility and order parameter for a superconductor with coupled magnetic
      impurities.

PMID- 9936147
TI  - Sensitivity of the critical magnetic field to phase shifts of paramagnetic
      impurities.

PMID- 9936146
TI  - Stochastic simulation of quantum systems and critical dynamics.

PMID- 9936148
TI  - Transfer-matrix method and Monte Carlo simulation in quantum spin systems.

PMID- 9936149
TI  - Linear-chain antiferromagnetism in FeOHSO4 and FeOHCrO4.

PMID- 9936150
TI  - Percolation with a threshold at zero: A new universality class.

PMID- 9936151
TI  - Monte Carlo study of polymerization on a lattice: Two dimensions.

PMID- 9936152
TI  - Interpretation of Dauphine-twin-domain configurations resulting from the alpha -
      beta phase transition in quartz and aluminum phosphate.

PMID- 9936153
TI  - A new kinetic walk and percolation perimeters.

PMID- 9936154
TI  - Domain growth and scaling in the Q-state Potts model.

PMID- 9936155
TI  - Localized magnetic moments on chromium and manganese dopant atoms in niobium and
      vanadium.

PMID- 9936156
TI  - Solitons in the paramagnetic and partially disordered phases of CsCoCl3.

PMID- 9936157
TI  - Theory for the early stages of phase separation: The long-range-force limit.

PMID- 9936158
TI  - Domain growth in the clock model.

PMID- 9936159
TI  - Rotational transitions in monolayer molecular solids.

PMID- 9936160
TI  - Theory of linear magnetoelastic effects.

PMID- 9936161
TI  - Application of a pseudo-one-dimensional kinetic Ising model to proton spin
      lattice relaxation rates in squaric acid (H2C4O4).

PMID- 9936162
TI  - Structural and magnetic instabilities in a twofold-degenerate band.

PMID- 9936164
TI  - Structure and electrochemistry of LixMo6S8.

PMID- 9936163
TI  - Corrections to finite-size-scaling laws and convergence of transfer-matrix
      methods.

PMID- 9936165
TI  - Long-range order for antiferromagnetic Potts models.

PMID- 9936166
TI  - Potts chain in a random field: An exact solution.

PMID- 9936167
TI  - Superconductivity in amorphous actinide alloys.

PMID- 9936168
TI  - Thermodynamics of the static approximation in the degenerate Hubbard model.

PMID- 9936169
TI  - Anisotropy in metallic spin glasses arising from gold impurities.

PMID- 9936170
TI  - Information theory and resistance fluctuations in one-dimensional disordered
      conductors.

PMID- 9936171
TI  - Thermodynamics of impure chains of classical spins with isotropic interactions.

PMID- 9936172
TI  - Vortex pairs in rotating 3He-A in a tilted magnetic field.

PMID- 9936173
TI  - Spin-1 exchange-interaction model of ferromagnetism.

PMID- 9936174
TI  - Disorder effects in ion-implanted niobium thin films.

PMID- 9936176
TI  - Monte Carlo coarse graining for the three-dimensional axial next-nearest-neighbor
      Ising model.

PMID- 9936175
TI  - Evidence for strong-coupling effects in the thermal conductivity of
      superconducting lead.

PMID- 9936177
TI  - Universal phase diagram for superconducting spin glasses.

PMID- 9936178
TI  - Pressure dependence of the transitions to the incommensurate phase of barium
      sodium niobate.

PMID- 9936179
TI  - New, organic, volume superconductor at ambient pressure.

PMID- 9936180
TI  - Direct observation of Coulomb correlation effects in polyacetylene.

PMID- 9936182
TI  - Comparison of models with competing interactions: Axial next-nearest-neighbor
      Ising versus two-plus-four spin interactions.

PMID- 9936181
TI  - Neutron scattering theory of intermediate-valence-Tm impurities.

PMID- 9936183
TI  - Physical interpretation of variables on the dual lattice.

PMID- 9936184
TI  - Quenched random-bond Ising ferromagnet: Anisotropic concentrations.

PMID- 9936185
TI  - Comment on "Metastability region in spin glasses"

PMID- 9936186
TI  - Interplay of exchange and crystal-field effects in the magnetic susceptibility of
      Cs2CrCl5

PMID- 9936187
TI  - Surface-interaction exponents for surface susceptibility: Renormalization-group
      crossover for chi 1.

PMID- 9936188
TI  - Erratum: Correlations in a two-dimensional quantunm electron gas: The ladder
      approximation

PMID- 9936189
TI  - Second-order quadrupolar echo.

PMID- 9936190
TI  - Electron-spin resonance, nuclear polarization, and spin relaxation of spin
      polarized atomic hydrogen.

PMID- 9936191
TI  - Coulomb effects in superconducting Kondo lattices.

PMID- 9936192
TI  - Inhomogeneity-induced anomalous critical fields in metastable three-dimensional
      alloys.

PMID- 9936194
TI  - Mean-field estimates of Tg for short-range spin glasses.

PMID- 9936193
TI  - Electronic structures of B1 MoN, fcc Mo2N, and hexagonal MoN.

PMID- 9936195
TI  - Correction to scaling exponent for the two-dimensional self-avoiding walk.

PMID- 9936196
TI  - Spectroscopic evidence against Rh 4d itinerant ferromagnetism in CeRh3B2.

PMID- 9936197
TI  - Instability under dilution of an antiferromagnetic Ising model on an fcc lattice:
      A Monte Carlo study.

PMID- 9936198
TI  - Transverse ordering in anisotropic spin glasses.

PMID- 9936199
TI  - Phase diagram for spontaneous nuclear magnetic ordering in copper.

PMID- 9936200
TI  - Glass transition in isopentane: A Monte Carlo study.

PMID- 9936201
TI  - Melting of sodium and potassium in a diamond anvil cell.

PMID- 9936202
TI  - High-pressure effects on the transport properties of the charge-density-wave
      compounds TaS3 and (TaSe4)2I.

PMID- 9936203
TI  - Quantum Monte Carlo study of a spin-1/2 chain.

PMID- 9936204
TI  - First observation of Altshuler-Aronov-Spivak effect in gold and copper.

PMID- 9936205
TI  - ESR and susceptibility studies of stage-I highly oriented pyrolytic graphite-OsF6
      graphite intercalation compound.

PMID- 9936206
TI  - Planar arrays of point charges with two- and three-dimensional backgrounds.

PMID- 9936207
TI  - Exact results for the charge and spin densities, exchange-correlation potentials,
      and density-functional eigenvalues.

PMID- 9936208
TI  - Electronic structure of copper-rich copper-gold alloys.

PMID- 9936210
TI  - Theory of electronic transport in random alloys: Korringa-Kohn-Rostoker coherent
      potential approximation.

PMID- 9936209
TI  - Electronic structure and anomalous properties of UAl2, NpAl2, and PuAl2.

PMID- 9936212
TI  - Theory of far-infrared absorption in small-metal-particle-insulator composites.

PMID- 9936211
TI  - Position and concentration dependence of the hydrogen-induced state on Pd(111).

PMID- 9936214
TI  - Self-consistent static-density-response function of a metal surface in density
      functional theory.

PMID- 9936213
TI  - Local-environment model for percolation in amorphous Mo-Si alloys.

PMID- 9936215
TI  - Surface-induced quantum density oscillations in the presence of an external
      magnetic field.

PMID- 9936217
TI  - Forward peaking and thermalization in the desorption of helium.

PMID- 9936216
TI  - Attenuated-total-reflection study of pyridine overlayers on silver films.

PMID- 9936218
TI  - State of Si and Sn in glassy Au alloys.

PMID- 9936219
TI  - Electronic coherence length following pulsed-laser annealing of Cu(001).

PMID- 9936220
TI  - Surface states on low-Miller-index copper surfaces.

PMID- 9936221
TI  - Photoemission, electronic structure, and magnetism in VPd3.

PMID- 9936222
TI  - Surface-enhanced Brillouin scattering on silver films.

PMID- 9936223
TI  - Origin of defect states on the surface of TiO2.

PMID- 9936224
TI  - Quantized Hall conductance as a topological invariant.

PMID- 9936225
TI  - Method to determine absolute amplitudes in the de Haas-van Alphen effect.

PMID- 9936226
TI  - Deuteron NMR relaxation rates in cerium deuterides.

PMID- 9936227
TI  - Scattering of He, Ne, Ar, H2, and N2 from Cu(110).

PMID- 9936228
TI  - Electronic structure of interstitial impurities near surfaces.

PMID- 9936229
TI  - Photoemission studies of carbon monoxide on tantalum-supported palladium thin
      films.

PMID- 9936231
TI  - Exact and approximate results for the ground-state energy of a Frohlich polaron
      in two dimensions.

PMID- 9936230
TI  - Hydrodynamic theory of density-response functions at a metal surface.

PMID- 9936232
TI  - Theory of the bimetallic interface.

PMID- 9936234
TI  - Breakdown of the random-phase approximation in the fractional-quantum-Hall-effect
      regime.

PMID- 9936233
TI  - Electronic and x-ray-absorption structure in compressed copper.

PMID- 9936236
TI  - Mixed-basis band-structure interpolation scheme applied to the fluorite-structure
      compounds NiSi2, AuAl2, AuGa2, and AuIn2.

PMID- 9936235
TI  - Surface melting of copper.

PMID- 9936237
TI  - Angle-resolved photoemission study of AuGa2 and AuIn2 intermetallic compounds.

PMID- 9936238
TI  - Surface phonon dispersion of c(2 x 2) S on Ni(100).

PMID- 9936239
TI  - Electronic polarizability of small metal spheres.

PMID- 9936240
TI  - Anisotropic thermal expansion in crystals with stacks of planar molecules, such
      as tetracyanoquinodimethanide (TCNQ) salts.

PMID- 9936241
TI  - Temperature dependence of the diffusion thermopower in metals.

PMID- 9936242
TI  - Transport and spectral properties of strongly disordered chains.

PMID- 9936243
TI  - Electromagnetic scattering, local field enhancements, and long-range surface
      plasmons in layered structures with roughness.

PMID- 9936244
TI  - High-temperature conductivity of one-dimensional electrons.

PMID- 9936245
TI  - Core-hole screening and plasmon satellites in calcium.

PMID- 9936246
TI  - Revised theory of relaxation ultrasound attenuation in glasses.

PMID- 9936247
TI  - Impurity and Landau-level electron lifetimes in n-type GaAs.

PMID- 9936248
TI  - Solid-phase crystallization kinetics in doped a-Si chemical-vapor-deposition
      films.

PMID- 9936249
TI  - Magnetothermopower of tetramethyltetrathiofulvalenium phosphorus hexaflouride

PMID- 9936250
TI  - Structureless transition and strong localization effects in bis
      tetramethyltetrathiafulvalenium salts

PMID- 9936252
TI  - Scanning tunneling microscope as a structure-modifying tool.

PMID- 9936251
TI  - Substitutional oxygen-oxygen pair in silicon.

PMID- 9936253
TI  - Determination of anomalous scattering factors in GaAs using x-ray refraction
      through a prism.

PMID- 9936254
TI  - Silicon interaction with low-electronegativity metals: Interdiffusion and
      reaction at the Ca/Si(111) interface.

PMID- 9936256
TI  - Electronic and vibronic states of the acceptor-bound-exciton complex (A0,X) in
      CdS. III. High-density electronic resonant Raman scattering at the (A0,X)
      complex.

PMID- 9936257
TI  - Far-infrared transmittance of boron-implanted germanium at liquid-helium
      temperatures.

PMID- 9936255
TI  - Electronic and vibronic states of the acceptor-bound-exciton complex (A0,X) in
      CdS. II. Determination of the fine structure of the (A0,XB) electronic states by
      high-resolution excitation spectroscopy.

PMID- 9936258
TI  - Many-body effects on the cyclotron resonance in a two-dimensional electron gas.

PMID- 9936259
TI  - Intercalation of silver in titanium disulfide.

PMID- 9936260
TI  - Theory of defect formation in the glow-discharge deposition of phosphorus-doped
      hydrogenated amorphous silicon.

PMID- 9936261
TI  - Capture processes at double donors in silicon.

PMID- 9936262
TI  - Auger-electron spectra from boron carbide.

PMID- 9936263
TI  - Structure and delocalized vibrational modes in vitreous Six(Se1-yTey)1-x.

PMID- 9936265
TI  - Energy levels of two- and three-dimensional polarons in a magnetic field.

PMID- 9936264
TI  - Band-structure calculation for GaAs and Si beyond the local-density
      approximation.

PMID- 9936266
TI  - Interference effects: A key to understanding forbidden Raman scattering by LO
      phonons in GaAs.

PMID- 9936267
TI  - Resonance Raman scattering by LO phonons in CdxHg1-xTe at the E0+ Delta 0 gap.

PMID- 9936268
TI  - Continuum model of a Peierls system with a complex order parameter.

PMID- 9936270
TI  - Lattice dynamics of mixed III-V crystals.

PMID- 9936269
TI  - Thermodynamic properties of liquid Si and Ge.

PMID- 9936271
TI  - Electronic structure of transition-atom impurities in GaP.

PMID- 9936272
TI  - Resonance Raman scattering in heavily-bulk-doped and ion-implanted laser-annealed
      n-type germanium.

PMID- 9936273
TI  - Two-loop study of the metal-insulator transition in the presence of weak magnetic
      scattering.

PMID- 9936274
TI  - Crossed diagrams for transport in substitutional binary alloys.

PMID- 9936275
TI  - Neutral (Cu-Li) complexes in GaP: The (Cu-Li)I bound exciton at 2.306 eV.

PMID- 9936276
TI  - Effect of interactions between electrons of like spin in conducting polymers.

PMID- 9936277
TI  - Thomas-Fermi dielectric screening of pseudocharges in semiconductors.

PMID- 9936278
TI  - Bulk and surface electronic structures of Si(111)2 x 1 and Si(111)7 x 7 studied
      by angle-resolved photoelectron spectroscopy.

PMID- 9936279
TI  - Photoemission study of the surface and bulk electronic structures of Si(111)7 x 7
      and Si(111) <= 3-bar x <= 3-bar:Al.

PMID- 9936280
TI  - Temperature dependence of the Shubnikov-de Haas effect in Hg1-xFexSe.

PMID- 9936281
TI  - Doping mechanism in a-Si:H.

PMID- 9936282
TI  - Weak-field magnetoresistance and substrate-induced strain in (111)-oriented PbTe
      films.

PMID- 9936283
TI  - Electronic charge distribution in silicon.

PMID- 9936285
TI  - Photoemission from activated gallium arsenide. II. Spin polarization versus
      kinetic energy analysis.

PMID- 9936284
TI  - Photoemission from activated gallium arsenide. I. Very-high-resolution energy
      distribution curves.

PMID- 9936286
TI  - Phonon-scattering-limited mobility in a quantum-well heterostructure.

PMID- 9936287
TI  - Electric-field-induced dissociation of excitons in semiconductor quantum wells.

PMID- 9936288
TI  - Effect of valence dielectric screening on ionized-impurity scattering in
      semiconductors.

PMID- 9936290
TI  - Theory of charge-state splittings of deep levels.

PMID- 9936289
TI  - Quasilocal impurity states in Pb1-xSnxTe and PbSe0.08Te0.92 liquid-phase
      epitaxial layers doped with group-III elements.

PMID- 9936291
TI  - Dissipative energy transfer during dynamic processes in stimulated desorption.

PMID- 9936293
TI  - Space charges and dipoles in rare-earth-doped SrF2.

PMID- 9936292
TI  - Theory of indirect hyperfine interactions of oxygen-aluminum defects in ionic
      crystals.

PMID- 9936294
TI  - Generalized hopping model for frequency-dependent transport in a dynamically
      disordered medium, with applications to polymer solid electrolytes.

PMID- 9936295
TI  - Far-infrared properties of lattice resonant modes. VII. Excited states and
      paraelectric pairs.

PMID- 9936297
TI  - Selective laser excitation of charge-compensated sites in KCl:Sm2+

PMID- 9936296
TI  - Elastic constants of barium fluoride from 300 to 1250 K.

PMID- 9936298
TI  - Effect of c-axis dispersion on the optical properties of acceptor-type graphite
      intercalation compounds.

PMID- 9936299
TI  - Optical properties of Cu+ ions in RbMgF3 crystals.

PMID- 9936300
TI  - Low-energy positron-diffraction study of NaF and LiF.

PMID- 9936301
TI  - Microscopic theory of light scattering from Goldstone (Q=0) phase modes and
      amplitude modes.

PMID- 9936302
TI  - Exchange-energy contribution to the interaction of helium with a metal surface.

PMID- 9936303
TI  - Binding energy of the 2p0-like level of a hydrogenic donor in GaAs-Ga1-xAlxAs
      quantum-well structures.

PMID- 9936304
TI  - Natural damping of nonlocal surface Bernstein modes in the high-magnetic-field
      quantum limit.

PMID- 9936305
TI  - Exciton recombination in amorphous chalcogenides.

PMID- 9936306
TI  - Resonant Raman scattering spectra of trans-(CD)x: Evidence for a distribution of
      conjugation lengths.

PMID- 9936307
TI  - Nonlinear Thomas-Fermi screening of donors in silicon.

PMID- 9936308
TI  - Soliton resonance in weak periodic fields.

PMID- 9936309
TI  - Vacuum ultraviolet reflectivity of small gold clusters.

PMID- 9936310
TI  - Elementary excitations in the fractional quantum Hall effect.

PMID- 9936312
TI  - Local-field effect in the biexciton system in CuCl.

PMID- 9936311
TI  - Inductive effects in transition-metal-compound core-electron satellite spectra.

PMID- 9936313
TI  - Erratum: Polaron effectivve mass in GaAs heterostructure

PMID- 9936314
TI  - Influence of adsorbates on surface magnetism studied by spin-resolved
      photoemission spectroscopy.

PMID- 9936315
TI  - X-ray photoelectron final-state screening in La(OH)3: A multiplet structural
      analysis.

PMID- 9936316
TI  - Neutron Kossel effect.

PMID- 9936317
TI  - Unoccupied surface resonance on Cu(100) and the effect of vacuum-level pinning.

PMID- 9936318
TI  - "Inductive" response from nonlinear mixing in sliding charge-density waves.

PMID- 9936319
TI  - Universal percolation-threshold limits in the continuum.

PMID- 9936320
TI  - Interface localization of excitons in CdTe/Cd1-xMnxTe multiple quantum wells.

PMID- 9936321
TI  - Existence of a universal low-energy tail in the photoluminescence of a-Si1-xGex:H
      alloys.

PMID- 9936322
TI  - Thermal relaxation of metastable strained-layer GexSi1-x/Si epitaxy.

PMID- 9936323
TI  - Identification of deep-gap states in a-Si:H by photo- depopulation-induced
      electron-spin resonance.

PMID- 9936324
TI  - Magneto-hot-electron transport for GaAs-Ga1-xAlxAs heterojunction in the extreme
      quantum limit.

PMID- 9936325
TI  - Photoluminescence and photoconductivity of CuInSe2.

PMID- 9936327
TI  - Origin of the current oscillations in GaAs-AlGaAs tunnel junctions.

PMID- 9936326
TI  - Temperature-dependent electronic excitations of the Si(111)2 x 1 surface.

PMID- 9936328
TI  - Electron-hole exchange transitions at defects in semiconduc- tors.

PMID- 9936330
TI  - Ab initio phonon dispersion curves of Si.

PMID- 9936329
TI  - Anisotropic optical-absorption studies of NbS2 single-layer suspensions aligned
      in a magnetic field.

PMID- 9936331
TI  - Local-density theory of mixed-valence TmSe and the valence transition in Tm
      chalcogenides.

PMID- 9936332
TI  - Polarization-dependent reflectivity of Si(111)-(2 x 1) surface above the gap.

PMID- 9936333
TI  - Field-induced disorder in the charge-density-wave state of K0.30MoO3.

PMID- 9936334
TI  - Hypersonic damping due to structural relaxation and fast-ion diffusion in (AgI)x
      (AgPO3)1-x melts.

PMID- 9936335
TI  - Photoluminescence studies of a GaAs-Ga1-xAlxAs superlattice at 8-300 K under
      hydrostatic pressure (0-70 kbar).

PMID- 9936336
TI  - Determination of the position and vibrational amplitude of an adsorbate by means
      of multiple-order x-ray standing-wave measurements.

PMID- 9936337
TI  - Measurement of positron reemission from thin single-crystal W(100) films.

PMID- 9936338
TI  - Depth-selective 57Fe conversion-electron Mossbauer spectroscopy. I. Theory
      improved accuracy, angular effects.

PMID- 9936339
TI  - Depth-selective 57Fe conversion-electron Mossbauer spectroscopy. II. Experimental
      test-angular effects, accuracy.

PMID- 9936341
TI  - Compton profile measurements with 662-keV gamma rays.

PMID- 9936340
TI  - Interpretation of the electron-energy-loss spectrum for hydrogen-covered
      transition-metal surfaces in terms of a configuration-interaction approach.

PMID- 9936342
TI  - Theory of nuclear magnetic resonance of higher-spin nuclei: A3B, A4B, and more
      complex spin-1 and spin-(3/2) systems.

PMID- 9936343
TI  - Nuclear-spin lattice relaxation and magnetic-ion spin fluctuations in Heisenberg
      antiferromagnets below TN.

PMID- 9936344
TI  - Slow-neutron scattering by molecular gases: A synthetic scattering function.

PMID- 9936345
TI  - Individual collision cascades in static bcc polycrystals.

PMID- 9936346
TI  - Effect of a magnetic field on the thermodynamics of dilute XY quantum chains.

PMID- 9936347
TI  - Functional derivative of the specific-heat difference near Tc for
      superconductors.

PMID- 9936348
TI  - Electron-spin resonance of atomic hydrogen and deuterium at low temperatures.

PMID- 9936350
TI  - Thermal conductivity of a strongly coupled plasma.

PMID- 9936349
TI  - Electrical conductivity of a strongly coupled plasma.

PMID- 9936351
TI  - I-V characteristics of microwave-driven Josephson junctions in the low-frequency
      and high-damping regime.

PMID- 9936352
TI  - Staging: A sampling technique for the Monte Carlo evaluation of path integrals.

PMID- 9936353
TI  - Theory of inhomogeneous quantum systems. I. Static properties of Bose fluids.

PMID- 9936354
TI  - Theory of inhomogeneous quantum systems. II. Linear response and collective
      excitations in Bose systems.

PMID- 9936355
TI  - Theory of inhomogeneous quantum systems. III. Variational wave functions for
      Fermi fluids.

PMID- 9936356
TI  - Renormalization-group theory of the Bose-Einstein condensation and a crossover in
      interacting systems.

PMID- 9936357
TI  - Microscopic approach to critical behavior in 3He-4He mixtures. II. Thermodynamics
      of the effective Hamiltonian.

PMID- 9936358
TI  - Magnetoresistance of a periodic superconducting network near Tc.

PMID- 9936360
TI  - Critical behavior with axially correlated random bonds.

PMID- 9936359
TI  - Transition layer in a lattice-gas model of a solid-melt interface.

PMID- 9936361
TI  - Calorimetric study of the trivalent Kondo compound TmS.

PMID- 9936363
TI  - Two-loop renormalization of Potts spin-glass.

PMID- 9936362
TI  - Directed aggregation on the Bethe lattice: Scaling, mappings, and universality.

PMID- 9936364
TI  - Magnetic structure and critical properties of FeGe2.

PMID- 9936366
TI  - Phase transitions in solids of diperiodic symmetry.

PMID- 9936365
TI  - Magnetic transitions in single-crystal Ho2Co17 studied in high magnetic fields.

PMID- 9936367
TI  - Susceptibility of spin-fluctuation compounds in high magnetic fields.

PMID- 9936369
TI  - Fluctuation-driven first-order transition in the short-range Potts spin glass.

PMID- 9936368
TI  - Thermodynamics of monolayer formation on an impure substrate: Random-field Ising
      model approach.

PMID- 9936370
TI  - Analytic continuation and appearance of a new phase for n<1 in n-component ( phi

PMID- 9936371
TI  - Critical proton and deuteron spin-lattice relaxation at the phase transition in p
      terphenyl.

PMID- 9936373
TI  - Two-dimensional Hubbard model: Numerical simulation study.

PMID- 9936372
TI  - Electronic and magnetic structure of ultrathin cobalt-chromium superlattices.

PMID- 9936374
TI  - Interpretation of the temperature dependence of the electron-paramagnetic
      resonance linewidth in Ag-Mn spin-glasses.

PMID- 9936375
TI  - Magnetostrictive torsional strain in transverse-field-annealed Metglas

PMID- 9936376
TI  - Anderson model in thermo field dynamics: Generalized Feynman-diagram method.

PMID- 9936378
TI  - Dipolar spin-wave modes of a ferromagnetic multilayer with alternating directions
      of magnetization.

PMID- 9936377
TI  - Kinetics of first-order phase transitions: Monte Carlo simulations,
      renormalization-group methods, and scaling for critical quenches.

PMID- 9936379
TI  - Dynamic correlations in the three-dimensional Ising model.

PMID- 9936380
TI  - Universal amplitude ratios for two-dimensional melting on smooth and periodic
      substrates.

PMID- 9936381
TI  - Privman-Fisher hypothesis on finite systems: Verification in the case of the
      spherical model of ferromagnetism.

PMID- 9936382
TI  - Magnetic form factor of the O2 molecule.

PMID- 9936383
TI  - Mossbauer spectroscopy study of the randomly mixed two-dimensional
      antiferromagnet with competing spin anisotropies K2CoxFe1-xF4.

PMID- 9936384
TI  - Ising model with competing axial interactions in the presence of a field: A
      renormalization-group treatment.

PMID- 9936386
TI  - Phase transitions in uniformly frustrated XY models.

PMID- 9936385
TI  - Numerical study of phonon localization in disordered systems.

PMID- 9936387
TI  - Reentrant melting of krypton adsorbed on graphite and the helical Potts-lattice
      gas model.

PMID- 9936388
TI  - Random-field critical behavior of a d=3 Ising system: Neutron scattering studies
      of Fe0.6Zn0.4F2.

PMID- 9936389
TI  - Neutron scattering study of the effect of a random field on the three-dimensional
      dilute Ising antiferromagnet Fe0.6Zn0.4F2.

PMID- 9936390
TI  - Critical scaling of the EPR linewidth in the Ag-Mn spin glass.

PMID- 9936391
TI  - Existence of an isotropic point and birefringence dispersion study in
      (C2H5NH3)2CuCl4 crystal near its thermochromic phase transition.

PMID- 9936392
TI  - Optical and x-ray studies on incommensurate phase transitions of ferroelectric
      ammonium fluoroberyllate (NH4)2BeF4.

PMID- 9936393
TI  - Crossover functions by renormalization-group matching: Three-loop results.

PMID- 9936394
TI  - Energetics of the incommensurate phase of krypton on graphite: A computer
      simulation study.

PMID- 9936396
TI  - Ground-state energy of a two-dimensional electron gas in a magnetic field:
      Hartree-Fock approximation.

PMID- 9936395
TI  - Polarized neutron study of the paramagnetic scattering from gamma -Fe.

PMID- 9936397
TI  - Anomalous temperature dependence of diffusion coefficient.

PMID- 9936398
TI  - Scaling and short-time corrections for random walks on two-dimensional exactly
      percolating clusters.

PMID- 9936399
TI  - Mictomagnetic, ferromagnetic, and antiferromagnetic transitions in La(FexAl1-x)13
      intermetallic compounds.

PMID- 9936400
TI  - Solitons and electroacoustic interactions in ferroelectric crystals. II.
      Interactions of solitons and radiations.

PMID- 9936401
TI  - Effect of target thickness on the He+ stopping power.

PMID- 9936402
TI  - Temperature dependences of the incommensurate wave-number parameters of all
      phases in the transition sequence (commensurate-->incommensurate-->

PMID- 9936403
TI  - Influence of damping in an electron gas on wake binding energies.

PMID- 9936404
TI  - High-pressure phase transition in CsCl at V/V0=0.53.

PMID- 9936406
TI  - Field dependence of the spin-glass susceptibility peaks in a Kaneyoshi-like
      effective-field model.

PMID- 9936405
TI  - Excluded-volume effects in linear polymers: Universality of generalized self
      avoiding walks.

PMID- 9936408
TI  - Anomalous behavior of PuAl2.

PMID- 9936410
TI  - Probing the spatial distribution of the energy gap in Josephson tunnel junctions.

PMID- 9936407
TI  - Spin-polarized photoelectron diffraction.

PMID- 9936409
TI  - First-order transition in systems of finite thickness.

PMID- 9936411
TI  - Stability of the nuclear polarization of H

PMID- 9936412
TI  - High-pressure structural phase transition in Mg.

PMID- 9936413
TI  - New fit of the 3He solid exchange parameters.

PMID- 9936414
TI  - Raman scattering on superconductors in the presence of charge-density states.

PMID- 9936415
TI  - Comments on "Magnetic phase transition, aggregate formation, and electrical
      conductivity of FeCl3-doped polyacetylene"

PMID- 9936416
TI  - Reply to "Comments on 'Magnetic phase transition, aggregate formation, and
      electrical conductivity in FeCl3-doped polyacetylene' "

PMID- 9936417
TI  - Comment on "Corrections to scaling for branched polymers and gels"

PMID- 9936418
TI  - Transverse Ising spin-glass model.

PMID- 9936419
TI  - Comment on "Ground state properties of a spin-1 antiferromagnetic chain"

PMID- 9936420
TI  - Erratum: Group-subgroup structural phase transitions: A comparison with existing
      tables

PMID- 9936421
TI  - Wetting by critical layers.

PMID- 9936422
TI  - Raman scattering from solid helium at high pressure.

PMID- 9936424
TI  - Random-loop expansion of the O(n) model on an arbitrary lattice.

PMID- 9936423
TI  - Unsuccessful search for time effects in the specific heat of spin-glass Cu-0.88
      at. %Mn.

PMID- 9936425
TI  - Monte Carlo studies of the quantum XY model in two dimensions.

PMID- 9936427
TI  - Critical wetting of surfaces in systems with long-range forces.

PMID- 9936426
TI  - Strong and weak electron spin-orbit scattering near the metal-insulator
      transition.

PMID- 9936428
TI  - Fractal eigendimensionalities for percolation clusters.

PMID- 9936430
TI  - Valence state of Ce and the magnetism in CeRh3B2.

PMID- 9936429
TI  - Anomalous voltage distribution of random resistor networks and a new model for
      the backbone at the percolation threshold.

PMID- 9936431
TI  - Critical dynamics of the kinetic Ising model on fractal geometries.

PMID- 9936432
TI  - Observation of an unoccupied surface state on Cu(110) by inverse photoemission.

PMID- 9936434
TI  - Electron-phonon interaction and the ground state of metallic hydrogen.

PMID- 9936433
TI  - Phonon dispersion in metallic glasses: A simple model.

PMID- 9936435
TI  - Magnetic-field-induced transition in quasi-two-dimensional systems.

PMID- 9936437
TI  - Theoretical investigation of the optical spectra of LiC6.

PMID- 9936436
TI  - Reflectivity spectra and dielectric function of stage-1 donor intercalation
      compounds of graphite.

PMID- 9936438
TI  - Orientation dependence of the carbon K edge in graphite measured by reflection
      electron-energy-loss spectroscopy.

PMID- 9936439
TI  - Structural and electronic trends in the growth of Cu overlayers on the Nb(110)
      surface.

PMID- 9936440
TI  - Infrared-absorption spectrum of an incommensurate charge-density wave: Potassium
      and sodium.

PMID- 9936441
TI  - Lattice dynamics of oxides with rutile structure and instabilities at the metal
      semiconductor phase transitions of NbO2 and VO2.

PMID- 9936442
TI  - Double occupancy of the f orbital in the Anderson model for Ce compounds.

PMID- 9936444
TI  - Interpretation of the N 1s photoelectron spectra of chemisorbed N2 in terms of
      local molecule-metal interactions.

PMID- 9936443
TI  - Ab initio cluster-model study of the electronic ground-state and photoemission
      properties of NiN2 and NiCO: Models for chemisorption.

PMID- 9936445
TI  - Vibrational relaxation and electronic energy transfer of N2 aggregates in solid
      Xe matrices.

PMID- 9936447
TI  - Thermal-expansion effects in electrical transport in amorphous metals.

PMID- 9936446
TI  - Localization effects in the scattering of light from a randomly rough grating.

PMID- 9936448
TI  - Density-functional-theory studies of correlation-energy effects at metallic
      surfaces.

PMID- 9936449
TI  - Radius, self-induced potential, and number of virtual optical phonons of a
      polaron.

PMID- 9936450
TI  - Second-harmonic generation from silver and aluminum films in total internal
      reflection.

PMID- 9936451
TI  - Phonon absorption of far-infrared radiation in small-metal-particle systems.

PMID- 9936452
TI  - Adsorbate-induced shifts of electronic surface states: Cs on the (100) faces of
      tungsten, molybdenum, and tantalum.

PMID- 9936453
TI  - Focusing of magnetoplasmon polaritons.

PMID- 9936454
TI  - Soluble models of rate processes in periodic systems with many degrees of
      freedom.

PMID- 9936455
TI  - Benzene chemisorption on palladium surfaces. I. High-resolution electron-energy
      loss vibrational spectra and structural models.

PMID- 9936457
TI  - Generalized coherent-potential method for disordered systems. II. Numerical
      results.

PMID- 9936456
TI  - Epitaxy and electronic structure of rho (1 x 1)Cr/Au(100).

PMID- 9936458
TI  - f-electron hybridization and heavy-fermion compounds.

PMID- 9936459
TI  - Low-energy excitonic resonances in metals. I. Experiments on divalent atoms.

PMID- 9936460
TI  - Low-energy excitonic resonances in metals. II. Cluster calculations for divalent
      impurities in Li metal.

PMID- 9936461
TI  - Resonant light scattering from a randomly rough surface.

PMID- 9936462
TI  - Self-consistent cluster calculation of binding energy and potential for positive
      muons in copper and copper-impurity systems.

PMID- 9936463
TI  - Electronic structure of intermetallic LiTl and NaTl.

PMID- 9936464
TI  - Theoretical study of the nonlinear response function describing optical second
      harmonic generation in nonlocal metal optics.

PMID- 9936465
TI  - Dislocation-enhanced induced Snoek peak associated with heavy interstitials in
      the presence of kinks moving harmonically in anisotropic body-centered-cubic
      metals.

PMID- 9936466
TI  - Extended x-ray-absorption fine-structure and near-edge-structure studies on
      evaporated small clusters of Au.

PMID- 9936467
TI  - White lines at K edges of light atoms.

PMID- 9936468
TI  - Determination of the structure factor of simple liquid metals from the
      pseudopotential theory and optimized random-phase approximation: Application to
      Al and Ga.

PMID- 9936469
TI  - Substitutional impurities in a linear chain with Peierls instability: Single
      impurity approach.

PMID- 9936471
TI  - Theoretical study of laser-induced surface excitations on a grating.

PMID- 9936470
TI  - Electronic-structure calculations for the Mo3(D3h) unit and its successive finite
      condensations Mo6(D3h,D3d,Oh), Mo9(D3h), and Mo12(D3d) up to the infinite chain
      (Mo6/2)

PMID- 9936472
TI  - Conduction in cosputtered Au-SiO2films.

PMID- 9936473
TI  - Coupled-cluster approach to electron correlation in one dimension. II. Cyclic
      polyene model in localized basis.

PMID- 9936475
TI  - Electromagnetic propagation in close-packed disordered suspensions.

PMID- 9936474
TI  - Many-body theory of indirect nuclear interactions.

PMID- 9936476
TI  - Surface states of ternary semiconductor alloys: Effect of alloy fluctuations in
      one-dimensional models with realistic atoms.

PMID- 9936477
TI  - Simplified electrostatic model for band-gap underestimates in the local-density
      approximation.

PMID- 9936478
TI  - Formation of surface superstructures by heat treatments on Ni-contaminated
      surface of Si(110).

PMID- 9936479
TI  - Energy dependence of the optical matrix element in hydrogenated amorphous and
      crystalline silicon.

PMID- 9936480
TI  - Charge disturbance around an impurity in silicon.

PMID- 9936481
TI  - Effect of a finite oxide layer on the Faraday rotation and ellipticity in a metal
      oxide-semiconductor system.

PMID- 9936482
TI  - Elastic constants and their pressure dependences in Cd1-xMnxTe with 0 <= x <=
      0.52 and in Cd0.52Zn0.48Te.

PMID- 9936483
TI  - Exciton transfer at low temperature in GaxIn1-xP:N and GaAs1-xPx:N.

PMID- 9936484
TI  - Quasiparticle spectrum of a Frohlich polaron in two dimensions.

PMID- 9936485
TI  - Dynamics of charge-density waves in orthorhombic TaS3.

PMID- 9936486
TI  - Guided acoustic-wave Brillouin scattering.

PMID- 9936487
TI  - Analysis of polaron effects in the cyclotron resonance of n-GaAs and AlGaAs-GaAs
      heterojunctions.

PMID- 9936488
TI  - Computer simulation of local order in condensed phases of silicon.

PMID- 9936489
TI  - Interpretation of low-energy Auger spectra from AlAs and GaAs(001): Applications
      to surface preparation.

PMID- 9936490
TI  - Exact results for the fractional quantum Hall effect with general interactions.

PMID- 9936491
TI  - Hot-electron galvanomagnetic conduction in n-InSb at 77 K.

PMID- 9936492
TI  - Reactions at a rare-earth-GaAs interface: Ce/GaAs(110).

PMID- 9936493
TI  - Role of strain energy in the stabilization of the 7 x 7 structure in the adatom
      model of the Si(111) surface.

PMID- 9936494
TI  - Dielectric matrices in semiconductors: A direct approach.

PMID- 9936495
TI  - Properties of fluorinated glow-discharge amorphous silicon.

PMID- 9936496
TI  - Diffusion-to-streaming transition of transport electrons in polar semiconductors.

PMID- 9936497
TI  - Structural properties of tetrahedrally coordinated crystals from first-principles
      calculations of pressure and total energies.

PMID- 9936498
TI  - Transport properties of highly doped polycrystalline and amorphous SnO2 films.

PMID- 9936499
TI  - Fine structure of acceptor-bound phonons in Raman spectra of ZnTe.

PMID- 9936501
TI  - Fluorinated hydrogenated amorphous silicon alloys. II. Electronic structure of
      pure and fluorinated silane chains.

PMID- 9936500
TI  - Critical development stages for the reactive Cr-GaAs(110) interface.

PMID- 9936502
TI  - 1S core-level spectroscopy of graphite: The effects of phonons on emission and
      absorption and validity of the final-state rule.

PMID- 9936503
TI  - Observation of exciton-exciton scattering in Cu2O by time-resolved
      photomodulation spectroscopy.

PMID- 9936504
TI  - Domain model of stage order and disorder in intercalation compounds.

PMID- 9936505
TI  - X-ray diffraction on (KBr)1-x(KCN)x mixed crystals.

PMID- 9936506
TI  - Temperature dependence of fluorescence spectra from x-ray-excited single-crystal
      CaF2:Mn(x) (x=0.1, 1.0, 3.0 at. %).

PMID- 9936507
TI  - Final-state screening and chemical shifts in photoelectron spectroscopy.

PMID- 9936508
TI  - Pressure dependence of elastic constants of (V1-xCrx)2O3 at 296 K.

PMID- 9936509
TI  - Effect of high pressure on the Raman and electronic absorption spectra of PbMoO4
      and PbWO4.

PMID- 9936510
TI  - Luminescence decay and electron traps in thermochemically reduced MgO.

PMID- 9936511
TI  - Two-photon absorption spectroscopy of multisite Gd3+ in CaF2.

PMID- 9936512
TI  - Optical spectroscopy of Pb2+ in NaCl: Validity of a Jahn-Teller (Fukuda) model.

PMID- 9936513
TI  - Fluctuating dipoles and polarizabilities in ionic materials: Calculations on LiF.

PMID- 9936514
TI  - Reaction-rate approach to the dipolar relaxation in alkali halides.

PMID- 9936515
TI  - Fully relativistic self-consistent energy bands of WSi2.

PMID- 9936516
TI  - Improved measurement of the far-infrared optical properties of semiconducting
      tetrathiafulvalene tetracyanoquinodimethane.

PMID- 9936517
TI  - Nature of covalent bonding of self-interstitials in silicon.

PMID- 9936519
TI  - Electronic characterization of the ordering of a-Ge with the use of x-ray
      absorption near-edge structure.

PMID- 9936518
TI  - Ferromagnetic Stoner excitations detected by electron-energy-loss spectroscopy.

PMID- 9936520
TI  - Heat capacity of free electrons at the degenerate-nondegenerate transition.

PMID- 9936522
TI  - Point-defect contribution to the low-frequency dielectric response of LiTaO3 at
      T>Tc.

PMID- 9936521
TI  - Phonons in cesium.

PMID- 9936523
TI  - Generalized spheroidal wave equations from an image-potential method for surface
      effects on impurity states.

PMID- 9936524
TI  - Recombination-induced heating of free carriers in a semiconductor.

PMID- 9936525
TI  - Experimental valence-band structure of tin disulfide SnS2.

PMID- 9936526
TI  - Phonon contribution to the ultrasonic attenuation in neutron-irradiated quartz.

PMID- 9936527
TI  - Temperature dependence of the polaron mass in AgBr.

PMID- 9936528
TI  - Effects of short-range order on electronic properties in a one-dimensional alloy
      model.

PMID- 9936529
TI  - Surface plasmon splitting on rough quenched Ag films.

PMID- 9936530
TI  - Lattice thermal conductivity of layered-structure compounds.

PMID- 9936531
TI  - Resistance fluctuation in a one-dimensional conductor with static disorder.

PMID- 9936532
TI  - Electronic structure of ultraheavily doped silicon.

PMID- 9936534
TI  - Orientation and dissociation of the CO molecule on transition-metal surfaces.

PMID- 9936533
TI  - Direct evidence of intervalley scattering in liquid-phase epitaxy AlxGa1-xAs/GaAs
      heterostructures.

PMID- 9936535
TI  - Erratum: Self-consistent relativistic calculation of the energy bands and
      cohesive energy of W

PMID- 9936536
TI  - Erratum: Self-consistent calculation of the polarizability of small jellium
      spheres

PMID- 9936537
TI  - Mechanism for hydrogen compensation of shallow-acceptor impurities in single
      crystal silicon.

PMID- 9936538
TI  - Hierarchy of plasmas for fractional quantum Hall states.

PMID- 9936539
TI  - Effect of Xe underlayers on surface-enhanced Raman scattering of pyridine on
      silver films deposited at low temperatures.

PMID- 9936540
TI  - Screening of polar interaction in quasi-two-dimensional semiconductor
      microstructures.

PMID- 9936541
TI  - Size quantization and band-offset determination in GaAs-GaAlAs separate
      confinement heterostructures.

PMID- 9936542
TI  - Picosecond and nanosecond laser-induced second-harmonic generation from
      centrosymmetric semiconductors.

PMID- 9936544
TI  - Defect reactions on the phosphorus sublattice in low-temperature electron
      irradiated InP.

PMID- 9936543
TI  - Persistent photoconductivity in a-Si:H/a-SiNx:H layered structures.

PMID- 9936546
TI  - Hole mobility in modulation-doped heterostructures: GaAs-AlGaAs.

PMID- 9936547
TI  - Donorlike excited states of the thermally induced 0.767-eV (P line) defect in
      oxygen-rich silicon.

PMID- 9936545
TI  - Electron-hole liquid as a true ground state.

PMID- 9936548
TI  - Surface reconstruction and lattice dynamics of hydrogenated Si(001):2 x 1.

PMID- 9936549
TI  - Electronic structure of an isolated GaAs-GaAlAs quantum well in a strong electric
      field.

PMID- 9936550
TI  - Resonant enhancement of the electric field in the grooves of bare metallic
      gratings exposed to S-polarized light.

PMID- 9936551
TI  - Phonons in amorphous semiconductor superlattices.

PMID- 9936552
TI  - Resonant photoemission and the mechanism of photon-stimulated ion desorption in a
      transition-metal oxide.

PMID- 9936553
TI  - Melting-induced electron localization: 133Cs NMR study of solid and liquid CsAu.

PMID- 9936554
TI  - Effects of thermal treatments on the lattice properties and electronic structure
      of ZrHx.

PMID- 9936555
TI  - Possible mechanisms for orthorhombic Jahn-Teller distortions of orbital triplets.

PMID- 9936557
TI  - Positron annihilation in helium- and krypton-decorated microvoids in fcc metals.

PMID- 9936556
TI  - Positron-beam-brightness enhancement: Low-energy positron diffraction and other
      applications.

PMID- 9936559
TI  - Temperature dependence of the 19F transferred hyperfine interaction in the EPR of
      Mn2+:PbF2.

PMID- 9936560
TI  - NMR of platinum catalysts: Double NMR of chemisorbed carbon monoxide and a model
      for the platinum NMR line shape.

PMID- 9936558
TI  - Deuteron and proton magnetic resonance in amorphous silicon.

PMID- 9936561
TI  - Nuclear quadrupole interaction due to point defects in aluminum: Effect of host
      lattice structure.

PMID- 9936562
TI  - Electron-spin-resonance study of Sn+(5p1) centers of the laser-active-type
      structure in KCl:Sn2+ and analysis of the hyperfine structure.

PMID- 9936563
TI  - Impurity-defect interaction in ion-implanted supersaturated Au-Fe alloys.

PMID- 9936571
TI  - Charge density of a vortex in the Coulomb-gas analogy of superconducting films.

PMID- 9936564
TI  - Interface-sensitive conversion-electron Mossbauer study of ion-beam mixing at the
      Fe-Al interface.

PMID- 9936565
TI  - Crystalline electric field at the rare-earth site in Chevrel-phase RMo6S8 and
      RMo6Se8 from Mossbauer spectroscopy.

PMID- 9936568
TI  - Josephson-junction arrays in transverse magnetic fields: Ground states and
      critical currents.

PMID- 9936569
TI  - Localization of acoustic waves.

PMID- 9936566
TI  - Electron-paramagnetic-resonance study of the Pd3+ Jahn-Teller ion in CaO.

PMID- 9936572
TI  - Itinerant-electron antiferromagnetism and superconductivity in bcc Cr-Re alloys.

PMID- 9936570
TI  - Magnetic and superconducting properties of holmium-rich (Er1-xHox)Rh4B4.

PMID- 9936573
TI  - Three-dimensional vortex dynamics in superfluid 4He: Line-line and line-boundary
      interactions.

PMID- 9936567
TI  - Thermal counterflow experiments on superfluid helium at temperatures close to T
      lambda.

PMID- 9936574
TI  - Subharmonic frequency locking in the resistive Josephson thermometer.

PMID- 9936575
TI  - Theory of Fermi-liquid effects in high-field tunneling.

PMID- 9936577
TI  - First-principles calculation of the dynamic structure factor for the electron gas
      in metallic systems.

PMID- 9936576
TI  - Nonlocal response of Josephson tunnel junctions to a focused laser beam.

PMID- 9936578
TI  - Universal relations among critical amplitudes of surface quantities.

PMID- 9936579
TI  - Spin and orbital magnetic densities in ferromagnetic nickel.

PMID- 9936580
TI  - Magnetic and magneto-optical properties of bismuth-substituted lutetium iron
      garnet films.

PMID- 9936581
TI  - Structural phase transitions in SbCl5-intercalated graphite.

PMID- 9936582
TI  - Effect of high magnetic fields on the heat capacity of single-crystal terbium.

PMID- 9936583
TI  - Paramagnetic spin fluctuations in the weak itinerant-electron ferromagnet MnSi.

PMID- 9936584
TI  - Exact solution for a one-dimensional chain of hindered dipoles with a transverse
      tunneling field.

PMID- 9936585
TI  - Critical behavior of the two-dimensional random-bond Ising model: A dynamic 1/T
      expansion.

PMID- 9936586
TI  - Determination of the critical exponents beta and gamma in iron by neutron
      depolarization.

PMID- 9936588
TI  - Physical realization of two-dimensional Ising critical phenomena: Oxygen
      chemisorbed on the W(112) surface.

PMID- 9936587
TI  - Magnetic-excitation behavior of CeBi and CeAs in the presence of a cubic crystal
      field or external magnetic field.

PMID- 9936589
TI  - Cellular interface morphologies in directional solidification. III. The effects
      of heat transfer and solid diffusivity.

PMID- 9936590
TI  - Cellular interface morphologies in directional solidification. IV. The formation
      of deep cells.

PMID- 9936591
TI  - Displacive modulation in the sinusoidal antiferroelectric phase of NaNO2.

PMID- 9936592
TI  - Phase diagrams and critical behavior of Ising square lattices with nearest-, next
      nearest-, and third-nearest-neighbor couplings.

PMID- 9936593
TI  - Two-dimensional Ising-like systems: Corrections to scaling in the Klauder and
      double-Gaussian models.

PMID- 9936594
TI  - High-pressure-induced phase transitions of mercury chalcogenides.

PMID- 9936595
TI  - Solitons of the square-rectangular martensitic transformation.

PMID- 9936596
TI  - Grain consolidation and electrical conductivity in porous media.

PMID- 9936597
TI  - Nonlinear modification of the hybridization interaction due to band polarization
      in the magnetically ordered state in f1 systems.

PMID- 9936598
TI  - Hybridization-mediated interaction and the equilibrium magnetic behavior in
      uranium monopnictides.

PMID- 9936599
TI  - Long-range random walk on percolation clusters.

PMID- 9936600
TI  - Dynamic correlations in a charged lattice gas.

PMID- 9936602
TI  - Magnetic transitions in dysprosium: A specific-heat study.

PMID- 9936601
TI  - Phase diagram of the one-dimensional molecular-crystal model with Coulomb
      interactions: Half-filled-band sector.

PMID- 9936603
TI  - Phase transition and high-pressure behavior of divalent metal oxides.

PMID- 9936604
TI  - Localization of kinks in a system of commensurability 3.

PMID- 9936605
TI  - Amplitude modulation of the supercurrent in Josephson junctions.

PMID- 9936607
TI  - Statistical model for stretched exponential relaxation in macroscopic systems.

PMID- 9936606
TI  - Tunneling and neutron scattering experiments on A15 V3Si.

PMID- 9936609
TI  - Magnetoresistance of yttrium alloys with dilute rare-earth solutes.

PMID- 9936608
TI  - Anderson localization and "universal" degradation of Tc in high-temperature
      superconductors.

PMID- 9936611
TI  - Thermal and nuclear hyperfine properties of Ho(OH)3.

PMID- 9936610
TI  - Excitonic molecule in the adiabatic representation.

PMID- 9936612
TI  - Reentrant magnetism: New aspects.

PMID- 9936614
TI  - Critical temperatures for a spin-1 Ising model with dipolar and quadrupolar
      interactions.

PMID- 9936613
TI  - Exact solution of a two-dimensional Ising model in a random magnetic field.

PMID- 9936615
TI  - Erratum: Low-temperature heat capacity of electrotransport-purified scandium,
      yttrium, gadolinium, and lutetium

PMID- 9936616
TI  - Further evidence for tunneling anisotropy in Nb crystals.

PMID- 9936617
TI  - Origin of Knight-shift anomaly in intermediate-valence compounds.

PMID- 9936619
TI  - Fermi surface of lithium studied by positron annihilation.

PMID- 9936618
TI  - Dynamics of dilute H in beta -phase palladium deuteride: A novel mass defect.

PMID- 9936620
TI  - Effects of oxygen on the upper critical fields of lead and tin molybdenum sulfide
      Chevrel phases.

PMID- 9936621
TI  - Elementary derivation of one-dimensional fermion-number fractionalization.

PMID- 9936622
TI  - Spin-fluctuation effects in the resistivity of Fe-Zr metallic glasses.

PMID- 9936623
TI  - Diffuse interface model of diffusion-limited crystal growth.

PMID- 9936624
TI  - Electron correlation effects on the magnetic-field-induced metal-insulator
      transition in Hg0.79Cd0.21Te.

PMID- 9936625
TI  - Initial-growth modes of nucleation droplets.

PMID- 9936626
TI  - First-principles approach for effective elastic-moduli calculation: Application
      to continuous fractal structure.

PMID- 9936627
TI  - Critical and multicritical wetting phenomena in systems with long-range forces.

PMID- 9936628
TI  - Surface free energies of three-dimensional Ising models and universality of
      finite-size scaling amplitudes by direct Monte Carlo sampling.

PMID- 9936629
TI  - Incommensurate structure and stability of mullite.

PMID- 9936631
TI  - Fractal character of eigenstates in weakly disordered three-dimensional systems.

PMID- 9936630
TI  - Bethe ansatz solution of a model for valence fluctuations between two magnetic
      configurations.

PMID- 9936632
TI  - Nonequilibrium superconductivity based on quasithermal phonon and quasiparticle
      distributions.

PMID- 9936633
TI  - NMR measurement of an ion in an excited state by indirect optical detection: A
      1G4 level of LiYF4:Pr3+

PMID- 9936634
TI  - Initial stages of silicon molecular-beam epitaxy: Effects of surface
      reconstruction.

PMID- 9936636
TI  - Light-induced metastable defects in hydrogenated amorphous silicon: A systematic
      study.

PMID- 9936635
TI  - Shapes of grain inclusions in crystals.

PMID- 9936637
TI  - EPR investigation of Cu2+ tetramers in ferroelectric CsH2PO4.

PMID- 9936638
TI  - Velocity spectrum of positronium thermally desorbed from an Al(111) surface.

PMID- 9936639
TI  - Isomer shifts and hyperfine fields in ferrous dihalides.

PMID- 9936640
TI  - Ligand electron-nuclear double resonance of 19F ions around Yb3+ impurities in
      fluorites.

PMID- 9936642
TI  - Photoinduced macroscopic quantum tunneling.

PMID- 9936641
TI  - Investigation of the Fe1+xSb system.

PMID- 9936643
TI  - Tin-doped bismuth: An inhomogeneous superconductor.

PMID- 9936644
TI  - Stabilizing effect of the static magnetic field and the threshold condition in
      the longitudinally driven NMR in superfluid 3He-B.

PMID- 9936645
TI  - Two-dimensional spin-polarized fermion lattice gases.

PMID- 9936646
TI  - Excitonic mechanism for superconductivity in a quasi-one-dimensional system.

PMID- 9936647
TI  - Coexistence of ordered magnetism and superconductivity in Pd2YbSn.

PMID- 9936649
TI  - Electromagnetic properties of proximity systems.

PMID- 9936648
TI  - Normal part of (H,T) phase diagram of a superconductor: Possible applications to
      proximity systems.

PMID- 9936650
TI  - Far-infrared determination of scattering behavior and plasma frequency in V3Si,
      Nb3Ge, and Nb.

PMID- 9936652
TI  - Determination of the Zeeman splitting in superconductors by Fourier analysis of
      tunneling data.

PMID- 9936651
TI  - Two-dimensional superconducting arrays in a magnetic field: Effects of lattice
      structures.

PMID- 9936654
TI  - New type of zero-field steps in the I-V curve of a Josephson junction of
      intermediate length.

PMID- 9936653
TI  - Spin-up problem in superfluid 4He.

PMID- 9936656
TI  - Calculations of the first- and second-correction-to-scaling amplitudes to order 6
      d in the percolation problem.

PMID- 9936655
TI  - Hybrid excitations in layered iron halides.

PMID- 9936657
TI  - Structural phase stability of B2 and B32 intermetallic compounds.

PMID- 9936659
TI  - Interface Hamiltonians and bulk critical behavior.

PMID- 9936658
TI  - Information-theoretic approach to high-temperature spin dynamics.

PMID- 9936661
TI  - 25-K phase transition in NpO2 from 237Np Mossbauer spectroscopy.

PMID- 9936660
TI  - Wetting transitions: A functional renormalization-group approach.

PMID- 9936663
TI  - Chaos-induced diffusive motion in a modeled-dislocation system: A scaling
      property of characteristic exponents.

PMID- 9936662
TI  - First-order transitions in anisotropic magnets with random fields and random
      uniaxial anisotropies.

PMID- 9936664
TI  - Interface moving through a random background.

PMID- 9936665
TI  - Uniaxial stress-induced symmetry breaking for muon sites in Fe.

PMID- 9936667
TI  - Macroscopic anisotropy in Dzyaloshinsky-Moriya spin glasses.

PMID- 9936666
TI  - Diffusion in a linear lattice with correlated random rates satisfying detailed
      balance.

PMID- 9936669
TI  - Spin-flip Raman scattering in n-type diluted magnetic semiconductors.

PMID- 9936668
TI  - Effects of kinematical interactions on magnon line broadening in a ferromagnet.

PMID- 9936670
TI  - An unusual phase transition.

PMID- 9936671
TI  - Monte Carlo study of the critical temperature of a two-dimensional,
      ferromagnetic, binary, Ising system.

PMID- 9936672
TI  - Critical behavior of the q-state Potts model with correlated random fields.

PMID- 9936673
TI  - Optical absorption spectra of the one-dimensional ferromagnet CsFeCl3.

PMID- 9936674
TI  - Ground state of an ion fluctuating between two magnetic valence states.

PMID- 9936675
TI  - Specific heat of dilute Cu-Mn alloys in the region of the spin-glass freezing
      temperature.

PMID- 9936676
TI  - Melting curves of molecular hydrogen and molecular deuterium under high pressures
      between 20 and 373 K.

PMID- 9936677
TI  - Spin-selective electron scattering and Auger emission in transition metals.

PMID- 9936678
TI  - A first-order phase transition in the face-centered-cubic Ising antiferromagnet.

PMID- 9936679
TI  - Dielectric-constant logarithmic correction in RbH2PO4 above the Curie point.

PMID- 9936680
TI  - Conduction-electron-spin polarization of ferromagnetic 4f and 5f systems: T
      matrix approach.

PMID- 9936681
TI  - Axial next-nearest-neighbor Ising (ANNNI) and extended-ANNNI models in external
      fields.

PMID- 9936682
TI  - Phase transitions and aging effects of the graphite intercalation compound alpha 
      C5n-HNO3.

PMID- 9936683
TI  - Light scattering by magnetic excitations in the mixed antiferromagnet Fe1-xMnxF2.

PMID- 9936684
TI  - Theory of melting and crystallization.

PMID- 9936686
TI  - Further proof for the second-derivative magnetic-resonance powder-spectrum
      method.

PMID- 9936685
TI  - First-order transitions breaking O(n) symmetry: Finite-size scaling.

PMID- 9936687
TI  - Tracer diffusion on two coupled lines: The long-time tail of the velocity
      autocorrelation function compared to the mode-coupling prediction.

PMID- 9936688
TI  - Phase-transition mechanism in RbH2PO4-type ferroelectrics.

PMID- 9936690
TI  - Semiflexible self-avoiding polymers: Low-temperature expansions for models.

PMID- 9936689
TI  - Wigner-distribution- and Green's-function approach to quantum corrections and
      implications for the melting temperature of two-dimensional Wigner crystals.

PMID- 9936691
TI  - Relationship between topological and magnetic order in small metal clusters.

PMID- 9936693
TI  - X-ray study of equations of state of solid xenon and cesium iodide at pressures
      up to 55 GPa.

PMID- 9936692
TI  - Linear-chain-like excitations in a three-dimensional Ising lattice with
      frustration: Monte Carlo simulations.

PMID- 9936694
TI  - Dynamic critical phenomena in fractals.

PMID- 9936695
TI  - Comment on: "Random-field Ising model on a Bethe lattice"

PMID- 9936696
TI  - Localization and scattering of acoustic waves in a one-dimensional random system:
      A proposed experiment.

PMID- 9936697
TI  - Further consequences of symmetry in heavy-electron superconductors.

PMID- 9936698
TI  - Reentrant phase diagram for granular superconductors.

PMID- 9936699
TI  - Scaling of the equilibrium boundary of three-dimensional random-field Ising-model
      systems.

PMID- 9936700
TI  - Direct observation of the triad longitudinal ESR mode in a spin glass.

PMID- 9936702
TI  - New phase in solid nitrogen at high pressures.

PMID- 9936701
TI  - Percolation properties of granular elastic networks in two dimensions.

PMID- 9936703
TI  - Critical slowing down in spin glasses and other glasses: Fulcher versus power
      law.

PMID- 9936705
TI  - Numerical evaluation of the partition function for one-dimensional quantum
      systems.

PMID- 9936704
TI  - Macromolecular chains subject to boundary constraints: Universal scaling
      amplitudes.

PMID- 9936706
TI  - Directed percolation in the two-dimensional continuum.

PMID- 9936708
TI  - Enhanced superconductivity in hydrogenated potassium-mercury-graphite
      intercalation compounds.

PMID- 9936707
TI  - Muonium centers in GaAs and GaP.

PMID- 9936709
TI  - Nonlinear magnetotransport and charge-density-wave motion in NbSe3 at
      temperatures from 1.2 to 50 K.

PMID- 9936711
TI  - Computer simulation of a quantum particle in a quenched disordered system: Direct
      observation of Lifshitz traps.

PMID- 9936710
TI  - Magnetic- and electric-field-induced transitions at high currents in NbSe3 at
      temperatures from 1.2 to 4.2 K.

PMID- 9936713
TI  - Critical evaluation of low-order moment expansions for the bonding energy of
      lattices and defects.

PMID- 9936712
TI  - Behavior of an electron in helium gas.

PMID- 9936714
TI  - Low-energy-electron-diffraction fine structure in W(001) for energies from 0 to
      35 eV.

PMID- 9936716
TI  - Analysis of the electronic pressure in transition and noble metals.

PMID- 9936715
TI  - Barrier diffusion and optical properties of the Au-Al2O3-Al thin-film system.

PMID- 9936717
TI  - Delocalization transition in random electrified chains with arbitrary potentials.

PMID- 9936719
TI  - Diffusion in mixed A-B alloys in two and three dimensions.

PMID- 9936718
TI  - Correlated diffusion in two-dimensional systems.

PMID- 9936721
TI  - Quantum Brownian motion in a periodic potential.

PMID- 9936720
TI  - Particle motion in a mixed dynamic alloy: Binary system in one dimension.

PMID- 9936722
TI  - Reassessment of the theory of stimulated Raman scattering.

PMID- 9936723
TI  - Dynamics of the reconstruction process Ir(100) 1 x 1-->1 x 5.

PMID- 9936724
TI  - Photoemission and electron-energy-loss spectroscopy investigation of CO

PMID- 9936725
TI  - Coupled surface plasmons in periodically corrugated thin silver films.

PMID- 9936726
TI  - Theory of the overlayer plasmon on the Si(001)2 x 1-K surface.

PMID- 9936727
TI  - Violation of sum rules by random-phase-approximation surface response
      calculations based on a density-functional ground-state description.

PMID- 9936728
TI  - Ultrasonic study of the vibrational modes of sintered metal powders.

PMID- 9936729
TI  - Bounds on the integrated density of electronic states for disordered
      Hamiltonians.

PMID- 9936731
TI  - Effects of edge anomaly on the appearance-potential spectroscopy of metals.

PMID- 9936730
TI  - Determination of the scattering potential for low energy alkali-metal ions from a
      Mo(001) surface.

PMID- 9936732
TI  - Vibrational spectra of coupled adsorbed molecules.

PMID- 9936733
TI  - Optical study of the metal-semiconductor transition in BaPb1-xBixO3.

PMID- 9936734
TI  - Bonding and magnetism of chemisorbed oxygen on Fe(001).

PMID- 9936735
TI  - Electron localization and interaction effects in palladium and palladium-gold
      films.

PMID- 9936736
TI  - Pd and Pt impurity-induced changes in noble-metal density of states:
      Photoelectron spectroscopy and theory.

PMID- 9936738
TI  - Ab initio cluster study of Ni adsorption on alumina.

PMID- 9936737
TI  - Neutron refractive index: A Fermi-Huygens theory.

PMID- 9936739
TI  - Grazing-incidence antireflection films. III. General theory for pure nuclear
      reflections.

PMID- 9936740
TI  - Grazing-incidence antireflection films. IV. Application to Mossbauer filtering of
      synchrotron radiation.

PMID- 9936741
TI  - Phase diagrams of systems exhibiting incommensurate structures.

PMID- 9936742
TI  - Temperature dependence of 1/f noise in metals.

PMID- 9936743
TI  - Self-consistent calculations of rare-gas-transition-metal interaction potentials.

PMID- 9936744
TI  - Electronic structure of ferromagnetic iron: Fermi surface.

PMID- 9936746
TI  - Theory of exciton-phonon coupling in one-dimensional molecular crystals: A
      variational treatment with delocalized solitary states.

PMID- 9936745
TI  - Partial structure factors and diffusion coefficients of liquid potassium-cesium
      alloys.

PMID- 9936747
TI  - Relaxation and nonradiative decay in disordered systems. I. One-fracton emission.

PMID- 9936749
TI  - New method to calculate the electronic properties of disordered materials.

PMID- 9936748
TI  - Two-beam dynamical diffraction solution of the phase problem: A determination
      with x-ray standing-wave fields.

PMID- 9936750
TI  - Time evolution of the dielectric function in a three-level system under pulsed
      excitation.

PMID- 9936751
TI  - New crystalline structures for Si and Ge.

PMID- 9936752
TI  - Electronic structure and bonding in ternary Zintl phases: LiAlSi.

PMID- 9936753
TI  - Dielectric response to a donor ion in a Ga1-xAlxAs-GaAs-Ga1-xAlxAs quantum well
      of infinite depth.

PMID- 9936754
TI  - Negative differential conductivity in shallow-impurity hopping.

PMID- 9936755
TI  - Valence charge density and effective charges within the density-response theory.

PMID- 9936757
TI  - Renormalization-group studies of the Hubbard-Peierls Hamiltonian for finite
      polyenes.

PMID- 9936756
TI  - Charge densities and quasi-ions in lattice dynamics.

PMID- 9936758
TI  - Magnetotunneling from accumulation layers in AlxGa1-xAs capacitors.

PMID- 9936759
TI  - Bulk and surface plasmons and localization effects in finite superlattices.

PMID- 9936761
TI  - Multiple-scattering theory of low-energy electron diffraction for a nonspherical
      scattering potential.

PMID- 9936760
TI  - Electronic properties of a shallow complex acceptor in CdTe.

PMID- 9936762
TI  - Electrical properties of dislocations and point defects in plastically deformed
      silicon.

PMID- 9936763
TI  - Generation of charge-density-wave conduction noise by moving phase vortices.

PMID- 9936764
TI  - Cody disorder: Absorption-edge relationships in hydrogenated amorphous silicon.

PMID- 9936765
TI  - Inelastic scattering of low-energy electrons from Sn overlayers on cleaved
      InSb(110) surfaces.

PMID- 9936766
TI  - Theory of transient excitonic optical nonlinearities in semiconductor quantum
      well structures.

PMID- 9936767
TI  - Structural properties and polarization charge densities of InSb.

PMID- 9936769
TI  - Contiguous two-dimensional regions in the quantized Hall regime.

PMID- 9936768
TI  - Refractive index of GaP and its pressure dependence.

PMID- 9936771
TI  - Lattice-dynamical model for the elastic constants and Raman frequencies in (V1
      xCrx)2O3.

PMID- 9936770
TI  - Holes at GaAs-AlxGa1-xAs heterojunctions in magnetic fields.

PMID- 9936772
TI  - Conduction-band states of TiS2 studied by means of polarized x-ray absorption.

PMID- 9936773
TI  - Optically detected magnetic resonance investigation of a deep Li-related complex
      in GaP.

PMID- 9936774
TI  - Model for persistent photoconductivity in doping-modulated amorphous silicon
      superlattices.

PMID- 9936775
TI  - Bulk electronic structure of germanium studied with angle-resolved photoemission.

PMID- 9936776
TI  - Electrical transport in pristine and heavily doped polyacenic materials.

PMID- 9936778
TI  - Raman scattering from ion-implanted silicon.

PMID- 9936777
TI  - Resonant photoemission from Cd1-xMnxSe: A probe of Mn 3d character and
      hybridization.

PMID- 9936780
TI  - Surface cyclotron resonance on InSb in Voigt configuration.

PMID- 9936779
TI  - Symmetry approach to the (P,T) diagram of TTF-TCNQ (tetrathiafulvalene
      tetracyanoquinodimethane).

PMID- 9936781
TI  - Electrical-conductivity changes in PbTe and PbSe films on exposure to the
      atmosphere.

PMID- 9936783
TI  - Phonon populations by nanosecond-pulsed Raman scattering in Si.

PMID- 9936782
TI  - Gallium-related 0.875-eV photoluminescence defect spectrum in irradiated silicon.

PMID- 9936784
TI  - Thermal conductivity and Raman spectra of carbon fibers.

PMID- 9936785
TI  - Resonant Raman scattering of the laser-active Tl0(1) center in alkali halides.

PMID- 9936786
TI  - Measurement of cation diffusion in magnesium oxide by determining the Mg 18O
      buildup produced by an electric field.

PMID- 9936788
TI  - Ionic potential models in insulators having the rutile structure.

PMID- 9936787
TI  - Surface electronic structure of NiO: Defect states, O2 and H2O interactions.

PMID- 9936789
TI  - Analysis of quasielastic light scattering in LiNbO3 near TC.

PMID- 9936790
TI  - Metallization of CsI under pressure: Theoretical results.

PMID- 9936791
TI  - In situ x-ray study of an acceptor-donor heterostructure: Stage-1 CoCl2-K
      graphite intercalation compound.

PMID- 9936792
TI  - Photon-stimulated desorption of neutral sodium from alkali halides observed by
      laser-induced fluorescence.

PMID- 9936794
TI  - Electron-spectroscopic manifestations of the 4f states in light rare-earth
      solids.

PMID- 9936793
TI  - Interphonon interactions at the charge-density-wave phase transitions in
      (TaSe4)2I and (NbSe4)2I.

PMID- 9936795
TI  - Monopole polarization in crystals.

PMID- 9936797
TI  - Structural and dynamical behavior of noble-gas surfaces.

PMID- 9936796
TI  - Influence of radiation intensity and lead concentration in the room-temperature
      coloring of KBr.

PMID- 9936799
TI  - Calculation of the free energy of defects in calcium fluoride.

PMID- 9936798
TI  - Role of atomic bonding for compound and glass formation in Ni-Si, Pd-Si, and Ni-B
      systems.

PMID- 9936800
TI  - Theory of low-temperature thermal expansion of glasses.

PMID- 9936801
TI  - Effects of vibrational optical activity in the reflection spectra of crystals for
      the frequency regions of nondegenerate vibrations.

PMID- 9936802
TI  - Direction-dependent initial-state relaxation in oxygen K x-ray emission.

PMID- 9936803
TI  - Comparison of adamantane and fluorite NiSi2.

PMID- 9936804
TI  - Possibility of incongruous interface behavior of In on GaAs(110).

PMID- 9936805
TI  - Binding energy of a donor in a quantum-well heterostructure.

PMID- 9936806
TI  - Binding energies of electrons by nitrogen pairs in GaP.

PMID- 9936808
TI  - Reply to "A comparison of analytic and Monte Carlo results in distant-pair
      recombination"

PMID- 9936807
TI  - Comparison of analytic and Monte Carlo results in distant-pair recombination.

PMID- 9936809
TI  - Erratum: Crystal-induced and image-potential-induced empty surface states on
      Cu(111) and Cu(001)

PMID- 9936810
TI  - Au-Si interface formation: The other side of the problem.

PMID- 9936811
TI  - Effect of a charged impurity on the fractional quantum Hall effect: Exact
      numerical treatment of finite systems.

PMID- 9936812
TI  - Incompressible states of the fractionally quantized Hall effect in the presence
      of impurities: A finite-size study.

PMID- 9936813
TI  - Chemical environment and Ce valence: Global trends in transition-metal compounds.

PMID- 9936814
TI  - Resistivity-noise measurements in thin gold films near the percolation threshold.

PMID- 9936815
TI  - High pressure as a probe of electron structure: Aluminum.

PMID- 9936816
TI  - ac response of pinned-charge-density-wave conductors.

PMID- 9936817
TI  - Optically detected magnetic resonance of triplet excited states in GaAs.

PMID- 9936818
TI  - Optically detected magnetic resonance of a localized spin-triplet midgap center
      in GaAs.

PMID- 9936819
TI  - Si(111)(7 x 7)-Ge and Si(111)(5 x 5)-Ge surfaces studied by angle-resolved
      electron-energy-loss spectroscopy.

PMID- 9936820
TI  - Magnetic-field-induced localization in InSb and Hg0.79Cd0.21Te.

PMID- 9936821
TI  - Epitaxy of silicon on nickel silicide.

PMID- 9936822
TI  - Photoemission study of the antibonding surface-state band on Si(111)2 x 1.

PMID- 9936823
TI  - Bound magnetic polarons in semimagnetic quantum wells.

PMID- 9936824
TI  - Reduced g factor of subband Landau levels in AlGaAs/GaAs heterostructures.

PMID- 9936825
TI  - Schottky barriers and semiconductor band structures.

PMID- 9936826
TI  - Giant enhancement of network coherence through mixed-alkali-metal-oxide addition
      to rapidly quenched vitreous silica.

PMID- 9936827
TI  - Equipotential distribution in the quantum Hall effect.

PMID- 9936828
TI  - Influence of a surface electric field on the line shape of the excitonic emission
      in GaAs.

PMID- 9936830
TI  - New surface polariton in spatially dispersive semiconductors.

PMID- 9936829
TI  - Plasmon-phonon coupling in a two-dimensional electron gas.

PMID- 9936831
TI  - Model adsorption potentials for He and Ne on graphite.

PMID- 9936832
TI  - Angle-resolved photoelectron spectra using realistic surface potentials: Evidence
      for surface-induced structure in TiC(001).

PMID- 9936833
TI  - Electronic interlayer states in hexagonal boron nitride.

PMID- 9936834
TI  - Diffusion of cesium in silver bromide: A surprising observation of the strain
      effect due to an oversize solute.

PMID- 9936836
TI  - Electron correlation and the band gap in ionic crystals.

PMID- 9936835
TI  - Hall effect in Ce1-xYxPd3 mixed-valence alloys.

PMID- 9936837
TI  - Sample variability of the temperature-dependent electrical resistivity of
      potassium below 1.3 K.

PMID- 9936838
TI  - Localization and homogeneous dephasing relaxation of quasi-two-dimensional
      excitons in quantum-well heterostructures.

PMID- 9936840
TI  - Equivalence of the A-B polymer and the general commensurate system.

PMID- 9936839
TI  - Temperature dependence of the quantized Hall effect.

PMID- 9936841
TI  - Spin dynamics in Ni near TC: A high-resolution neutron scattering study.

PMID- 9936842
TI  - Axial sites of Ni3+ and Cr3+ in MgO:Li,Ni single crystals.

PMID- 9936843
TI  - Positronium formation and diffusion in crystalline and amorphous ice using a
      variable-energy positron beam.

PMID- 9936845
TI  - Anisotropic diffusion in benzene: 13C NMR study.

PMID- 9936844
TI  - Relaxation of 29-cm-1 phonons in ruby.

PMID- 9936846
TI  - Electron paramagnetic resonance of the incommensurate cooperative Jahn-Teller
      compound Tl2PbCu(NO2)6.

PMID- 9936847
TI  - Spin delocalization in phosphorus donor pairs in silicon.

PMID- 9936848
TI  - Observation of exchange coupling in the EPR spectrum of Mn2+ in FeSiF6

PMID- 9936849
TI  - Phason narrowing of the nuclear magnetic resonance in potassium.

PMID- 9936850
TI  - Zeeman spectroscopy of the vanadium luminescence in GaP and GaAs.

PMID- 9936851
TI  - Comparison of slow-tumbling ESR theories for completely asymmetric hyperfine
      centers undergoing orientational diffusion.

PMID- 9936853
TI  - Electron-nuclear double resonance of titanium in silicon: 29Si ENDOR.

PMID- 9936852
TI  - Electronic excitation of oriented molecules by low-energy electrons: An
      application to H2.

PMID- 9936854
TI  - Triad spectroscopy via ultraviolet up-conversion in Pr3+:LaF3.

PMID- 9936856
TI  - Hyperfine-field contributions of s-type orbitals in iron.

PMID- 9936855
TI  - Exchange narrowing of NMR line shapes in randomly diluted magnetic systems.

PMID- 9936857
TI  - Evidence for precursory electron localization in dirty bulk metallic alloys.

PMID- 9936858
TI  - Thermal accommodation of atomic hydrogen with a liquid-4He surface.

PMID- 9936859
TI  - Perpendicular upper critical field of superconducting-normal-metal multilayers.

PMID- 9936860
TI  - Fluctuation effects on critical behavior of Josephson-junction arrays.

PMID- 9936861
TI  - Elementary excitations in dilute mixtures of 3He in superfluid 4He.

PMID- 9936863
TI  - Goldstone phonons in a Bose-condensed gas at finite temperature: One-loop
      approximation.

PMID- 9936862
TI  - Spin waves in H

PMID- 9936865
TI  - Free energy in the coexistence region of superconductivity and magnetic order.

PMID- 9936864
TI  - Nonasymptotic critical behavior from field theory at d=3: The disordered-phase
      case.

PMID- 9936866
TI  - Free-fermion approach to the commensurate-incommensurate transition in a model of
      Si/W(110).

PMID- 9936867
TI  - Spin clusters and random local anisotropy in mictomagnetic Au-Fe alloys.

PMID- 9936868
TI  - Essentially perturbative quantities in the Kondo model.

PMID- 9936870
TI  - Quantum decimation for spin-(1/2) chains in a magnetic field.

PMID- 9936869
TI  - Moments of the total magnetization and conformal invariance in the finite two
      dimensional Ising model.

PMID- 9936872
TI  - Theory for the nucleation of a crystalline droplet from the melt.

PMID- 9936871
TI  - Magnetic behavior of free-iron and iron oxide clusters.

PMID- 9936873
TI  - Sine-Gordon kinks in dynamic structure functions.

PMID- 9936875
TI  - Spin susceptibilities of a one-dimensional disordered quantum Heisenberg
      antiferromagnet.

PMID- 9936874
TI  - Effect of d-band mixing in Mn-transition-metal spin glasses.

PMID- 9936876
TI  - Geometrical factor and thermal properties of a sublattice dilute Potts model.

PMID- 9936877
TI  - Static and dynamic real-space renormalization through series expansions for
      correlation functions.

PMID- 9936878
TI  - Gutzwiller treatment applied to antiferromagnetic states of small aggregates.

PMID- 9936879
TI  - Effect of disorder on a fractal model for the ac response of a rough interface.

PMID- 9936880
TI  - Phase diagram of NdSb: Type-I fcc antiferromagnet in a magnetic field.

PMID- 9936881
TI  - Orientational order in xenon fluid monolayers on single crystals of exfoliated
      graphite.

PMID- 9936882
TI  - Dynamics of three-dimensional Ising spin glasses in thermal equilibrium.

PMID- 9936883
TI  - Scaling in an interacting two-component (valence-fluctuation) electron gas.

PMID- 9936885
TI  - Theory of coupled phason and sound-wave normal modes in the incommensurate phase
      of quartz.

PMID- 9936884
TI  - Properties of Dauphine-twin domain walls in quartz and berlinite.

PMID- 9936886
TI  - Scattering by inhomogeneous systems with rough internal surfaces: Porous solids
      and random-field Ising systems.

PMID- 9936887
TI  - Nonlinear susceptibility and relaxation in the XY spin glass Y Tb.

PMID- 9936888
TI  - Anderson clusters and inhomogeneous ordering in the short-range Ising spin glass.

PMID- 9936889
TI  - Low-temperature thermal expansion of single-Q chromium and of dilute
      antiferromagnetic CrV alloys.

PMID- 9936890
TI  - Hydrodynamics of icosahedral quasicrystals.

PMID- 9936891
TI  - Commensurate-incommensurate phase transitions and wetting in a lattice-gas model
      with axially competing interactions.

PMID- 9936892
TI  - Hamiltonian studies of the Blume-Emery-Griffiths model.

PMID- 9936893
TI  - XY antiferromagnetic ordering in CoCl2

PMID- 9936895
TI  - Symmetry of Bloch functions in the space group D4h6 of perfect antiferromagnetic
      chromium.

PMID- 9936894
TI  - Pressure study of the magnetic and electrical properties of the Eu-Yb alloy
      system.

PMID- 9936896
TI  - Magnetic transitions and scaling behavior in Gd-rich glasses.

PMID- 9936897
TI  - Dimensional crossover calculation at the multicritical point for spatial
      dimension d=3: An application to quantum ferroelectrics.

PMID- 9936899
TI  - Variational approach to the spin-1 anisotropic Heisenberg chain.

PMID- 9936898
TI  - Dynamics of a particle in an external potential interacting with a dissipative
      environment.

PMID- 9936900
TI  - Magnetic behavior of as-quenched and hydrogenated amorphous Fe92Zr8.

PMID- 9936901
TI  - Josephson arrays in an incommensurate magnetic field.

PMID- 9936902
TI  - Nature of the staging transformation in graphite intercalation compounds.

PMID- 9936903
TI  - Integral hierarchies and percolation.

PMID- 9936904
TI  - Finite-size effects on the W(001) low-temperature phase transition.

PMID- 9936905
TI  - Interfacial critical phenomena at semipermeable membranes.

PMID- 9936907
TI  - Comparison of the elastic moduli and the conductivity observed in a two
      dimensional percolating system.

PMID- 9936906
TI  - Empirical evidence of a nonuniversal Kosterlitz-Thouless jump for frustrated two
      dimensional XY models.

PMID- 9936908
TI  - Neutron thermalization in H2O and D2O with the use of a synthetic scattering
      function.

PMID- 9936909
TI  - Experimental relationship between damping and stability of sine-Gordon solitons
      in Josephson junctions.

PMID- 9936910
TI  - Near-surface defect profiling with slow positrons: Argon-sputtered Al(110).

PMID- 9936911
TI  - Anomalous thermal boundary resistance of superfluid 3He-B.

PMID- 9936913
TI  - Soft-x-ray emission intensities in UIr3, UPt3, and UAu3.

PMID- 9936912
TI  - Anomalous s-wave proximity-induced Josephson effects in UBe13, CeCu2Si2, and
      LaBe13: A new probe of heavy-fermion superconductivity.

PMID- 9936914
TI  - Thin films of anisotropic superconductors.

PMID- 9936915
TI  - Direct observation of spin fluctuations in the heavy-fermion system UPt3.

PMID- 9936916
TI  - Fluxoid quantization in knotted superconductors.

PMID- 9936917
TI  - Local superconductivity in ultrathin Sn films.

PMID- 9936918
TI  - Josephson phase transition.

PMID- 9936920
TI  - Critical effects in the reversible, nonlinear susceptibility of PdMn spin
      glasses.

PMID- 9936919
TI  - Effect of boundary conditions on the critical behavior of a fi- nite high
      dimensional Ising model.

PMID- 9936922
TI  - Direct observations of first-order magnetization processes in single-crystal
      Nd2Fe14B.

PMID- 9936921
TI  - Character of the magnetic order in epsilon - and delta -phase O2 monolayers on
      graphite.

PMID- 9936923
TI  - Metastable states, domain walls, domain-flip transitions, and inhomogeneous
      ordering in the short-range Ising spin glass.

PMID- 9936924
TI  - Helium compressional effect on H2 molecules surrounded by dense H2-He mixtures.

PMID- 9936925
TI  - NMR spin-echo spectra of icosahedral quasicrystals.

PMID- 9936927
TI  - Measurement of the conductivity exponent in two-dimensional percolating networks:
      square lattice versus random-void continuum.

PMID- 9936926
TI  - Renormalization-group study of interfacial properties and its applications to an
      Ising spin glass.

PMID- 9936928
TI  - Selection of stable fixed points by the Toledano-Michel symmetry criterion: Six
      component example.

PMID- 9936929
TI  - Local-orbital analysis of oxygen-oxygen interaction on nickel (001) from self
      consistent electronic structure.

PMID- 9936930
TI  - Electronic band-structure hybridization in the heavy-fermion superconductor UPt3.

PMID- 9936931
TI  - Compton profiles for polycrystalline CuxNi1-x alloys: Theory and experiment.

PMID- 9936932
TI  - Application of sum rules to the response of small metal particles.

PMID- 9936933
TI  - Electronic structure and Fermi surface of calcium.

PMID- 9936935
TI  - Edge magnetoplasmons in a bounded two-dimensional electron fluid.

PMID- 9936934
TI  - Unoccupied-state electronic structure in (NiyPt1-y)75P25 and Ni100-xPx metallic
      glasses.

PMID- 9936937
TI  - Fourth-order gradient contributions in extended Thomas-Fermi theory for
      noninteracting fermions at finite temperature.

PMID- 9936936
TI  - Calculation of the surface segregation of Ni-Cu alloys with the use of the
      embedded-atom method.

PMID- 9936938
TI  - Spectral analysis of adsorbate induced field-emission flicker noise.

PMID- 9936939
TI  - Lattice relaxation in high-temperature pure crystalline materials and
      substitutionally disordered alloys. I. Multiple-scattering formalism for
      displaced atoms.

PMID- 9936940
TI  - Lattice relaxation in high-temperature pure crystalline materials and
      substitutionally disordered alloys. II. Self-consistent treatment of distortion
      and related problems.

PMID- 9936941
TI  - Anomalous frequency-dependent transport in composites.

PMID- 9936943
TI  - Optical and electrical properties of single-crystalline zirconium carbide.

PMID- 9936942
TI  - Time- and frequency-dependent behavior of a two-dimensional electron gas at long
      wavelengths.

PMID- 9936944
TI  - Supercell calculations of the valence photoemission spectra of CeSb, PrSb, and
      NdSb.

PMID- 9936945
TI  - Spin polarization of secondary electrons in transition metals: Theory.

PMID- 9936946
TI  - Comparison of two techniques in the theory of phonon-induced cyclotron resonance
      line shapes.

PMID- 9936947
TI  - Chemisorption-induced changes in surface magnetism and electronic structure:
      Oxygen on Ni(110).

PMID- 9936948
TI  - Heat of solution in stressed metal alloys and grain-boundary segregation: Al1
      xZnx.

PMID- 9936949
TI  - Melting of stressed metal alloys and grain-boundary melting: Al1-xZnx.

PMID- 9936950
TI  - Linearized augmented-plane-wave calculation of the electronic structure and total
      energy of tungsten.

PMID- 9936951
TI  - Vibrational properties of model monatomic crystals under pressure.

PMID- 9936952
TI  - Localization in two- and three-dimensional systems away from the band center.

PMID- 9936953
TI  - In-plane intercalate dynamics in alkali-metal graphite intercalation compounds.

PMID- 9936954
TI  - Comparison between extended x-ray-absorption and extended electron energy-loss
      fine-structure results above the M2,3 edge of cobalt.

PMID- 9936955
TI  - Surface electronic structure of CeN.

PMID- 9936956
TI  - Dynamics of metallic-surface and dipole interaction in the presence of optical
      Johnson noise.

PMID- 9936957
TI  - Weak localization and anharmonicity of phonons.

PMID- 9936958
TI  - Green functions for superlattices.

PMID- 9936960
TI  - Quantum size and nonlocal effects in the electromagnetic properties of small
      metallic spheres.

PMID- 9936959
TI  - Nonlocal kinetic energy functional for nonhomogeneous electron systems.

PMID- 9936961
TI  - Scattered impurity states in transition metals. I. Exploitation of the point
      group symmetry for the linear-combination-of-atomic-orbitals method.

PMID- 9936963
TI  - Thermal conductivity and shear viscosity of anharmonic doped crystals: An
      improved fundamental approach.

PMID- 9936962
TI  - Scattered impurity states in transition metals. II. Approximate solutions using
      phase shifts.

PMID- 9936965
TI  - Mechanism of elastic shear coefficients of dilute copper alloys.

PMID- 9936964
TI  - Sound-wave velocities in liquid alkali metals studied at temperatures up to 150
      degreesC and pressures up to 0.7 GPa.

PMID- 9936966
TI  - Theoretical study of electrical conduction in finite metals and insulators.

PMID- 9936967
TI  - Two-dimensional polaron in a magnetic field.

PMID- 9936968
TI  - Magnetic susceptibility study of boron carbides.

PMID- 9936970
TI  - Theoretical study of stacking faults in silicon.

PMID- 9936969
TI  - Comparison of fully relativistic energy bands and cohesive energies of MoSi2 and
      WSi2.

PMID- 9936971
TI  - Calculation of bulk moduli of diamond and zinc-blende solids.

PMID- 9936972
TI  - Piezospectroscopic study of Be double acceptors in Ge.

PMID- 9936973
TI  - Bulk and surface valence in YbPdx compounds.

PMID- 9936974
TI  - Inelastic extended-electron-localized-vibrational-state scattering rate.

PMID- 9936976
TI  - Activity coefficient and Einstein relation for different densities of states in
      semiconductors.

PMID- 9936975
TI  - Electron transfer between regions of quasi-two-dimensional and three-dimensional
      dynamics in semiconductor microstructures.

PMID- 9936977
TI  - Absorption coefficients and exciton oscillator strengths in AlGaAs-GaAs
      superlattices.

PMID- 9936979
TI  - Far-infrared spectrum of di-tetramethyltetraselenafulvalene hexafluoroarsenate

PMID- 9936978
TI  - Surface quenching of optically generated carriers in thin-film hydrogenated
      amorphous silicon: Picosecond transient-grating experiments.

PMID- 9936980
TI  - Thermal conductivity of mercury telluride.

PMID- 9936982
TI  - Electronic properties and bonding sites for chlorine chemisorption on Si(111)-(7
      x 7).

PMID- 9936981
TI  - Surface core-level shifts for clean and halogen-covered Ge(100) and Ge(111).

PMID- 9936983
TI  - Green's-function formalism of electronic states in heavily doped semiconductors
      and its application to a problem of inter-valence-band absorption.

PMID- 9936984
TI  - Electronic Raman scattering in heavily doped p-type germanium.

PMID- 9936985
TI  - Far-infrared magnetoabsorption study of electron systems in Ga0.47In0.53As-InP
      heterojunctions.

PMID- 9936987
TI  - Effective-mass theory of resonant Raman scattering by semiconductor donors.

PMID- 9936986
TI  - Theoretical model of the Au-Fe complex in silicon.

PMID- 9936988
TI  - Interface chemistry of ternary semiconductors: Local morphology of the Hg1
      xCdxTe(110)-Cr interface.

PMID- 9936990
TI  - Photoluminescence of Cd1-xMnxTe-CdTe multiple-quantum-well structures and
      superlattices in a magnetic field.

PMID- 9936989
TI  - Optical dephasing and excitation transfer of an impurity-bound exciton in a
      semiconductor: Photon-echo experiments on GaP:N.

PMID- 9936991
TI  - Quantum and classical mobility determination of the dominant scattering mechanism
      in the two-dimensional electron gas of an AlGaAs/GaAs heterojunction.

PMID- 9936992
TI  - Violation of the Peierls theorem in graphite chains.

PMID- 9936993
TI  - Impurity cluster states in disordered two-dimensional systems: A self-consistent
      Hartree-Fock-Roothaan model.

PMID- 9936994
TI  - Frequency-dependent conductivity in sputtered amorphous phosphorus thin films.

PMID- 9936995
TI  - Photoelectron paramagnetic resonance studies of the nature of donor-acceptor pair
      recombination processes in ZnS:Cr,Sc.

PMID- 9936996
TI  - Surface roughness at the Si(100)-SiO2 interface.

PMID- 9936997
TI  - Image potential of a two-dimensional electron gas.

PMID- 9936998
TI  - Hopping theory of band-tail relaxation in disordered semiconductors.

PMID- 9936999
TI  - Influence of indirect minima on electron concentration in GaAs-AlxGa1-xAs
      superlattices: A numerical study.

PMID- 9937000
TI  - Electron-energy-loss spectroscopy of multilayered materials: Theoretical aspects
      and study of interface optical phonons in semiconductor superlattices.

PMID- 9937001
TI  - Potassium-doped polyacetylene studied by photoelectron and metastable quenching
      spectroscopy.

PMID- 9937002
TI  - Photoluminescence study of localization effects induced by the fluctuating random
      alloy potential in indirect band-gap GaAs1-xPx.

PMID- 9937003
TI  - Photoconductivity and dark-conductivity studies of CdS1-xSex(Cu) sintered layers.

PMID- 9937004
TI  - Thermal phonon scattering at singlet-triplet donor states in cubic
      semiconductors.

PMID- 9937005
TI  - Anomalies observed in the shallow acceptor states in GaAs.

PMID- 9937007
TI  - Polarized hot-electron photoluminescence in highly doped GaAs.

PMID- 9937006
TI  - Optical response of YbS and YbO at high pressures and the pressure-volume
      relation of YbS.

PMID- 9937008
TI  - Correlation of EPR and thermoluminescence in crystals of highly colored CaO:Mg:
      Involvement of a center containing hydrogen ions.

PMID- 9937009
TI  - Relaxational and anharmonic contributions to sound-velocity behavior in
      superionic glasses.

PMID- 9937010
TI  - Band-edge features in disordered systems.

PMID- 9937011
TI  - Electronic structure of crystalline and amorphous silicon dioxide.

PMID- 9937012
TI  - Decay process of Li 1s core exciton in lithium halides studied by photoelectron
      spectroscopy.

PMID- 9937013
TI  - Charge-transfer optical absorption in linear magnetic insulators in a strong
      electric field.

PMID- 9937015
TI  - Zirconium nitride-a new material for Josephson junctions.

PMID- 9937014
TI  - Sine-Gordon solitons under weak stochastic perturbations.

PMID- 9937016
TI  - Angle-resolved ultraviolet photoelectron spectroscopy of the unoccupied band
      structure of graphite.

PMID- 9937017
TI  - Dislocation polarization and space-charge relaxation in solid solutions Ba1
      xLaxF2+x.

PMID- 9937018
TI  - Electronic structure of amorphous Si3N4 in the cluster-Bethe-lattice
      approximation.

PMID- 9937019
TI  - Phonon assistance in tunneling for nonideal lattice dynamics.

PMID- 9937020
TI  - Raman study of phonon anharmonicity in LaF3.

PMID- 9937022
TI  - Magnetic-breakdown coupling between orbits of a low-electron-density system.

PMID- 9937021
TI  - Two-photon absorption spectroscopy of Eu2+ ions in KCl and KI.

PMID- 9937023
TI  - Packing and chemical effects in amorphous Fe-Zr and Fe-B alloys.

PMID- 9937025
TI  - Surface-plasmon dispersion in the infinite-barrier model.

PMID- 9937026
TI  - Orthogonalized linear combinations of atomic orbitals. III. Extension to f
      electron systems.

PMID- 9937024
TI  - Lattice dynamics of bcc Sr.

PMID- 9937027
TI  - Remarkable periodicity of Gen p ions (n/p <~ 25, 1 <= p <= 4) formed by the
      liquid-metal ion-source technique.

PMID- 9937028
TI  - Phenomenological approach to the electronic structure of glassy transition-metal
      alloys.

PMID- 9937029
TI  - Mobility edges in a one-dimensional system with incommensurate potentials.

PMID- 9937030
TI  - Circular dichroism in photoelectron angular distributions from adsorbed atoms.

PMID- 9937031
TI  - Photopyroelectric measurement of the thermal diffusivity of solids.

PMID- 9937033
TI  - Spikes in the orbital magnetic susceptibility of a two-dimensional electron gas.

PMID- 9937032
TI  - Reappraisal of the band-edge discontinuities at the AlxGa1-xAs-GaAs
      heterojunction.

PMID- 9937035
TI  - Inverse photoemission from PdH0.65.

PMID- 9937034
TI  - Direct experimental evidence for monosilane formation after proton or deuteron
      implantation of crystalline silicon.

PMID- 9937036
TI  - Dimer formation at the earlier stage of dipole clustering in manganese-doped NaCl
      and KCl.

PMID- 9937037
TI  - Optimally smooth norm-conserving pseudopotentials.

PMID- 9937038
TI  - Soft acoustic modes in trigonal crystals.

PMID- 9937039
TI  - Dielectric breakdown between parallel plates.

PMID- 9937040
TI  - Erratum: Surface correlation energy and the hydrodynamic model of dynamic,
      nonlocal bounded plasma response

PMID- 9937042
TI  - Transient charge-density-wave dynamics in NbSe3.

PMID- 9937041
TI  - Aharonov-Bohm effect in disordered metals with interactions.

PMID- 9937043
TI  - Interaction of CO molecules adsorbed on stepped platinum surfaces.

PMID- 9937044
TI  - Dynamics of adsorbate core-hole decay.

PMID- 9937045
TI  - Many-particle exchanges and the fractional quantized Hall effect.

PMID- 9937046
TI  - Single-particle relaxation time versus scattering time in an impure electron gas.

PMID- 9937047
TI  - Inertial charge-density-wave dynamics in (TaSe4)2I.

PMID- 9937048
TI  - Optically detected cyclotron resonance in a GaAs/Ga0.67Al0.33As superlattice.

PMID- 9937049
TI  - New evidence of extensive valence-band mixing in GaAs quantum wells through
      excitation photoluminescence studies.

PMID- 9937050
TI  - Tunneling images of the 5 x 5 surface reconstruction on Ge-Si(111).

PMID- 9937051
TI  - Conductivity in the fractionally quantized Hall effect.

PMID- 9937052
TI  - Cesium graphite intercalation compound study from angle-resolved photoemission
      spectroscopy.

PMID- 9937053
TI  - Excitons trapped at impurity centers in highly ionic crystals.

PMID- 9937055
TI  - Atomic geometry of the 2 x 2 GaP(111) surface.

PMID- 9937054
TI  - Persistent photoconductivity in doping-modulated multilayers and compensated thin
      films of hydrogenated amorphous silicon.

PMID- 9937056
TI  - Experimental results on the high-field thermopower of a two-dimensional electron
      gas in a GaAs-Ga1-xAlxAs heterojunction.

PMID- 9937057
TI  - Core-level x-ray photoemission: Deviations from threshold behavior.

PMID- 9937058
TI  - Electron orbits in an impure metal in the presence of a strong magnetic field.

PMID- 9937059
TI  - Localization and interaction effects in anisotropic disordered electronic
      systems.

PMID- 9937060
TI  - Energy-band-structure studies of NbN(100) and VN(100).

PMID- 9937061
TI  - Atomic structure of the Cu/Si(111) interface by high-energy core-level Auger
      electron diffraction.

PMID- 9937062
TI  - X-ray-edge problem in metals. I. Universal scaling in alkali-alkali alloys.

PMID- 9937064
TI  - X-ray absorption near-edge structure and extended x-ray absorption fine-structure
      investigation of Pd silicides.

PMID- 9937063
TI  - X-ray-edge problem in metals. II. Alkali-metal atoms adsorbed on alkali and other
      metal surfaces.

PMID- 9937065
TI  - Unusual diffuse scattering intensities from nitrogen in niobium.

PMID- 9937067
TI  - Current distributions in the quantum Hall effect.

PMID- 9937066
TI  - Continued-fraction coefficients in the presence of critical points.

PMID- 9937068
TI  - Ordering tendency inside a surface segregation: Application to Pt-Ni alloys.

PMID- 9937069
TI  - Low-energy-electron transmission through epitaxial films: Cu(001) on Ni(001).

PMID- 9937070
TI  - Local-orbital analysis of the oxygen-nickel (001) bond from self-consistent
      electronic structure.

PMID- 9937072
TI  - Phonon dispersion curves of bcc Ba.

PMID- 9937071
TI  - Localization and interaction effects in thin titanium films.

PMID- 9937073
TI  - Depolarization effects in Raman scattering from cyanide on silver-island films.

PMID- 9937074
TI  - Incommensurate icosahedral density waves in rapidly cooled metals.

PMID- 9937075
TI  - Fano antiresonances in x-ray-absorption spectroscopy.

PMID- 9937076
TI  - Analysis of positron-annihilation data in Cu and alpha -Cu1-xGex alloys.

PMID- 9937077
TI  - Optical properties and microstructure of gold-fluorocarbon-polymer composite
      films.

PMID- 9937078
TI  - Molecular dynamics calculation of elastic constants for a crystalline system in
      equilibrium.

PMID- 9937079
TI  - 1/f noise of metals: A case for extrinsic origin.

PMID- 9937080
TI  - Quantum transport theory for high electric fields.

PMID- 9937081
TI  - Band model for the electronic structure of KHgC8.

PMID- 9937082
TI  - Dephasing effects in a simple magnetic-breakdown linked-orbit network.

PMID- 9937084
TI  - Finite-temperature aspects of the quantum Hall effect: A Boltzmann-equation
      approach.

PMID- 9937083
TI  - Optical transmittance and reflectance and dynamic current density for thin
      metallic films.

PMID- 9937085
TI  - Diffuse scattering of high-frequency phonons at solid surfaces.

PMID- 9937086
TI  - Dimensionality crossover induced by a magnetic field in thin metallic films.

PMID- 9937087
TI  - Generalized relativistic cubic harmonics.

PMID- 9937089
TI  - Improved bipartition model of electron transport. I. A general formulation.

PMID- 9937088
TI  - Theory of the surface tension of liquid metal alloys.

PMID- 9937091
TI  - Momentum-resolved inverse photoemission study of nickel surfaces.

PMID- 9937090
TI  - Improved bipartition model of electron transport. II. Applications to
      inhomogeneous media.

PMID- 9937092
TI  - Mean-trajectory approximation for charge- and energy-transfer processes at
      surfaces.

PMID- 9937093
TI  - Reference-plane positions for substrate-mediated dispersion energies.

PMID- 9937094
TI  - Structural information from the Raman spectrum of amorphous silicon.

PMID- 9937095
TI  - Theoretical analyses of space-charge doping in amorphous semiconductor
      superlattices. I. Doping superlattices.

PMID- 9937096
TI  - Theoretical analyses of space-charge doping in amorphous semiconductor
      superlattices. II. Compositional superlattices.

PMID- 9937097
TI  - Interference of electric-dipole and magnetic-dipole interactions in conduction
      electron-spin resonance in InSb.

PMID- 9937098
TI  - Inversion asymmetry and magneto-optical selection rules in n-type zinc-blende
      semiconductors.

PMID- 9937099
TI  - Transient photoluminescence and excited-state optical absorption in trigonal
      selenium.

PMID- 9937101
TI  - Raman scattering by intervalley carrier-density fluctuations in n-type Si:
      Intervalley and intravalley mechanisms.

PMID- 9937100
TI  - Electronic structure and Schottky-barrier formation of Ag on n-type GaAs(110).

PMID- 9937102
TI  - Raman scattering by intervalley carrier-density fluctuations in n-type Ge:
      Uniaxial stress and resonance effects.

PMID- 9937104
TI  - Electron-phonon scattering in superlattices.

PMID- 9937103
TI  - Electronic structure of copper, silver, and gold impurities in silicon.

PMID- 9937105
TI  - Adatom aggregation, reaction, and chemical trapping at the Sm/GaAs(110)
      interface.

PMID- 9937107
TI  - Subband structure of n-type accumulation and inversion layers in GaAs-Ge
      heterojunctions.

PMID- 9937106
TI  - Laser-induced glass-crystallization phenomena of GeSe2 investigated by light
      scattering.

PMID- 9937108
TI  - Optical properties of Ag-related centers in bulk ZnSe.

PMID- 9937109
TI  - Dielectric response of a semi-infinite layered electron gas and Raman scattering
      from its bulk and surface plasmons.

PMID- 9937110
TI  - Resonant Raman scattering at the saddle-point singularity in InxGa1-xAs.

PMID- 9937112
TI  - Resonant neutralization of ions scattered from surfaces in the intermediate
      velocity regime.

PMID- 9937111
TI  - New kind of noise in photoconductors.

PMID- 9937114
TI  - Electronic structure and impurity-limited electron mobility of silicon
      superlattices.

PMID- 9937113
TI  - Model for the metastable system of type (GaAs)1-x(Ge2)x.

PMID- 9937115
TI  - Resonant-Brillouin-scattering linewidth in a weak magnetic field: Direct evidence
      for the k-linear effect in the A exciton in CdS.

PMID- 9937117
TI  - Vibrational properties of amorphous silicon in the frequency range 250-450 cm-1.

PMID- 9937116
TI  - Electric field dependence of optical absorption near the band gap of quantum-well
      structures.

PMID- 9937119
TI  - Temperature-dependent growth morphology of a semiconductor-metal interface:
      Ge/Ta(110).

PMID- 9937118
TI  - Intervalley effective-mass theory: Pseudopotential formulation.

PMID- 9937120
TI  - Radiative electron-hole recombination in a new sawtooth semiconductor
      superlattice grown by molecular-beam epitaxy.

PMID- 9937121
TI  - Absorption near band edges in heavily doped GaAs.

PMID- 9937122
TI  - Hole mobility of GaAs, GaP, and GaAs1-xPx mixed-compound semiconductors.

PMID- 9937123
TI  - Green's-function approach to nonlinear electronic transport for an electron
      impurity-phonon system in a strong electric field.

PMID- 9937124
TI  - Effect of random potential fluctuations on electron transport in n-type InSb.

PMID- 9937125
TI  - High-frequency conductivity of type-I superlattices.

PMID- 9937127
TI  - Magneto-optical study of Li and Na acceptor bound excitons in CdTe: Fine
      structure and cubic crystal-field effect.

PMID- 9937126
TI  - Theoretical investigation of the pressure dependences of energy gaps in
      semiconductors.

PMID- 9937128
TI  - Effect of metal substitution in ZrSe3-type compounds: Vibrational states of Zr1
      tHftS3.

PMID- 9937129
TI  - Hot holes in naphthalene: High, electric-field-dependent mobilities.

PMID- 9937130
TI  - Longitudinal Hall effect in SrAs3.

PMID- 9937131
TI  - Low-temperature donor-acceptor recombination in silver halides.

PMID- 9937132
TI  - Ab initio study of the autocorrelation function for lithium nitride.

PMID- 9937133
TI  - Electronic structures of lithium metasilicate and lithium disilicate.

PMID- 9937134
TI  - Low-temperature behavior of potassium borate glasses.

PMID- 9937135
TI  - Raman scattering study of interactions of cyanide impurities in KCl under
      variation of temperature and concentration.

PMID- 9937137
TI  - Valence- and conduction-band structure of the sapphire (11-bar02) surface.

PMID- 9937136
TI  - Interlayer binding of hexagonal boron nitride in the rigid-layer approximation.

PMID- 9937138
TI  - Optical dephasing by nonequilibrium phonons in LaF3.

PMID- 9937139
TI  - Analysis of low-energy electron transmission experiments through thin solid xenon
      films in the elastic scattering region.

PMID- 9937140
TI  - Noise-power studies of the nearly commensurate quasi-one-dimensional conductor (N
      methylphenazinium)x(phenazine)1-x (7,7,8,8-tetracyano-p-quinodimethane)

PMID- 9937141
TI  - Two fully bleachable zero-phonon-line defects in NaF: Possible candidates for
      highly efficient photochemical hole burning.

PMID- 9937143
TI  - Optical reflectance study of the electronic structure of acceptor-type graphite
      intercalation compounds.

PMID- 9937142
TI  - High-efficiency photochemical hole burning for an infrared color center.

PMID- 9937144
TI  - Calculations of the electronic properties of substoichiometric Ti-Fe hydride.

PMID- 9937145
TI  - Satellites in x-ray photoelectron spectroscopy of insulators. I. Multielectron
      excitations in CaF2,SrF2, and BaF2.

PMID- 9937146
TI  - Satellites in x-ray photoelectron spectroscopy of insulators. II. Multielectron
      excitations in LiF, NaF, and KF.

PMID- 9937148
TI  - Paramagnon contribution to the inelastic scattering time in two-dimensional
      disordered metals.

PMID- 9937147
TI  - Scaling of conductivities in the fractional quantum Hall effect.

PMID- 9937149
TI  - Luminescence line shape of amorphous hydrogenated carbon and silicon.

PMID- 9937151
TI  - Band-gap narrowing in heavily doped silicon at 20 and 300 K studied by
      photoluminescence.

PMID- 9937150
TI  - Phonon focusing in cubic crystals in which transverse phase velocities exceed the
      longitudinal phase velocity in some direction.

PMID- 9937152
TI  - Determination of the gap-state distribution of hydrogenated amorphous silicon
      alloys from sub-band-gap absorption measurements.

PMID- 9937153
TI  - Formation of Ag2S under Ag-paint electrodes in contact with TaS3.

PMID- 9937154
TI  - Surface states on Si(111) sqrt 3-bar x sqrt 3-bar-In: Experiment and theory.

PMID- 9937155
TI  - Conductivity sensitivity of inelastic scanning tunneling microscopy.

PMID- 9937156
TI  - Non-muffin-tin band theories of the multiple-scattering type.

PMID- 9937157
TI  - Response to "non-muffin-tin band theories of the multiple-scattering type"

PMID- 9937158
TI  - Comment on "Optical-transition cross sections involving impurities in
      semiconductors"

PMID- 9937160
TI  - Erratum: Theory of hydrogen and helium impurities in metals

PMID- 9937159
TI  - Reply to "Comment on 'Optical-transition cross sections involving impurities in
      semiconductors' "

PMID- 9937161
TI  - Erratum: Localized and delocalized two-dimensional excitons in GaAs-AlGaAs
      multiple-quantum-well structures

PMID- 9937163
TI  - Structure and properties of a beryllium dilayer.

PMID- 9937162
TI  - Erratum: Origin of the current oscillations in GaAs-AlGaAs tunnel junctions

PMID- 9937164
TI  - Ellipsoidal shell structure in free-electron metal clusters.

PMID- 9937165
TI  - Amorphous Ni-Zr alloys as barriers for self-diffusion.

PMID- 9937166
TI  - Photoionization and shell structure of potassium clusters.

PMID- 9937167
TI  - Temperature dependence of positron diffusion in metals.

PMID- 9937168
TI  - Theory of tunneling of an atom interacting with a degenerate electron gas.

PMID- 9937169
TI  - Two-component density-functional theory: Application to positron states.

PMID- 9937170
TI  - Energy-resolved photofield emission from the W(100) surface state.

PMID- 9937171
TI  - Nuclear gamma -ray resonance observations in an aluminum-based icosahedral
      quasicrystal.

PMID- 9937172
TI  - Electronic structure of LiZnN: Interstitial insertion rule.

PMID- 9937173
TI  - New optical structure near the E transitions of InSb/InAlSb quantum wells.

PMID- 9937174
TI  - Surface morphology of GaAs(110) by scanning tunneling microscopy.

PMID- 9937175
TI  - Irreversibility and nonequilibrium dynamics in the pinned charge-density wave.

PMID- 9937176
TI  - Screening and elementary excitations in narrow-channel semiconductor
      microstructures.

PMID- 9937178
TI  - Optical intracenter excitations of the PGa antisite defect in GaP.

PMID- 9937177
TI  - Indirect band gap of coherently strained GexSi1-x bulk alloys on <001> silicon
      substrates.

PMID- 9937179
TI  - Second-order Raman scattering by confined optical phonons and interface
      vibrational modes in GaAs-AlAs superlattices.

PMID- 9937180
TI  - Linear response and the quantized Hall effect.

PMID- 9937181
TI  - High-density excitonic state in two-dimensional multiple quantum wells.

PMID- 9937182
TI  - Raman spectra of diamond at high pressures.

PMID- 9937183
TI  - Experimental evidence for nonintegral direct-force valence in electromigration.

PMID- 9937185
TI  - Patterns of relaxation in disordered materials.

PMID- 9937184
TI  - Molecular-orbital-self-consistent-field cluster model of H2O adsorption on
      copper.

PMID- 9937187
TI  - High-field backward-wave phonon spectroscopy of Si:In.

PMID- 9937186
TI  - Computer renormalization-group calculation for the fractionally quantized Hall
      effect.

PMID- 9937188
TI  - Ultrasonic response of dilute AlFe alloys irradiated with 2.5-MeV electrons.

PMID- 9937190
TI  - Raman scattering of light from a charge-density-wave (CDW) phonon in an
      anisotropic CDW superconductor.

PMID- 9937189
TI  - Large ternary-metal contributions to the wave functions at the Fermi level in
      TlMo6Se8.

PMID- 9937191
TI  - X-ray edges of superconducting metals.

PMID- 9937192
TI  - Specific heat of thin-film amorphous molybdenum-based alloys.

PMID- 9937193
TI  - Statistical mechanics of pentagonal and icosahedral order in dense liquids.

PMID- 9937195
TI  - Simulation studies of radiation linewidth in circular Josephson-junction fluxon
      oscillators.

PMID- 9937194
TI  - Fractal structure of the complete devil's staircase in dissipative systems
      described by a driven damped-pendulum equation with a distorted potential.

PMID- 9937196
TI  - Superconductivity and crystal and electronic structures in hydrogenated and
      disordered Nb3Ge and Nb3Sn layers with A15 structure.

PMID- 9937197
TI  - Birefringence measurements of the uniaxial-stress dependence of the
      incommensurate phase transition in K2SeO4.

PMID- 9937198
TI  - Some developments in the theory of modulated order. I. The role of fluctuations
      in the axial next-nearest-neighbor Ising model and the relevance of the Thouless
      Anderson-Palmer equation.

PMID- 9937199
TI  - Some developments in the theory of modulated order. II. Deformable-lattice models
      and the axial next-nearest-neighbor Ising model as a random magnet.

PMID- 9937200
TI  - Wetting transitions in systems with van der Waals forces.

PMID- 9937201
TI  - Breakdown of self-similar scaling in the two-dimensional random-field Ising
      model: A Monte Carlo study.

PMID- 9937202
TI  - Low-temperature phase of a stacked triangular Ising antiferromagnet.

PMID- 9937203
TI  - Variational approach to finite-temperature magnetism.

PMID- 9937204
TI  - Theory of photoelectron spectra from inner-core states. II. Temperature effect
      and role of d-electron correlations.

PMID- 9937205
TI  - Statistical mechanics of a fractal lattice: Renormalization-group analysis of the
      Sierpinski gasket.

PMID- 9937206
TI  - Magnetic properties of PtFe alloys calculated by Monte Carlo methods.

PMID- 9937208
TI  - Specific heat of CsNiF3.

PMID- 9937207
TI  - Temperature-dependent domain-growth kinetics of orientationally ordered phases:
      Effects of annealed and quenched vacancies.

PMID- 9937210
TI  - Nonlinear optical properties of Rb2ZnCl4 in the incommensurate and ferroelectric
      phases.

PMID- 9937209
TI  - Possible commensurate structures for TaTe4 and related compounds.

PMID- 9937211
TI  - Adsorption of CCl4 on graphite.

PMID- 9937213
TI  - Ferromagnetic and transmission resonance in magnetic metal superlattices.

PMID- 9937212
TI  - Absorption and magneto-optical properties of the 3A2g--> 1T2ga transition in
      CsNiF3. II. Pure-exciton and hot-magnon bands in a one-dimensional ferromagnet.

PMID- 9937214
TI  - Low-temperature electrical resistivity of pseudobinary alloys based on UAl2.

PMID- 9937215
TI  - Brillouin scattering study of the elastic properties of incommensurate barium
      sodium niobate.

PMID- 9937216
TI  - Temperature dependence of the magnetic excitations in gadolinium.

PMID- 9937217
TI  - Finite-size scaling in the three-dimensional Ising model.

PMID- 9937218
TI  - Critical effects at complete wetting.

PMID- 9937219
TI  - Supercurrent in 3He-B.

PMID- 9937220
TI  - Mossbauer spectroscopic studies of Nd2Fe14B.

PMID- 9937221
TI  - Experimental and theoretical investigations of the magnetic susceptibility and
      anisotropy of Nd(OH)3.

PMID- 9937222
TI  - Heuristic generalization of the Bogolyubov-Tyablikov magnetization equation to
      arbitrary isotropic spin Hamiltonians.

PMID- 9937224
TI  - Phase transitions in fully frustrated spin systems.

PMID- 9937223
TI  - Time scale of thermally activated diffusion in random systems: A new law of
      thermal activation.

PMID- 9937225
TI  - Critical dynamics of the kinetic Ising model on the fractal Koch curves.

PMID- 9937227
TI  - NMR study of the charge-density-wave state in single-crystal Rb0.30MoO3: The
      effect of an applied electric field.

PMID- 9937226
TI  - Linked-cluster expansion for quantum spin systems and the perpendicular
      susceptibility of the Ising model.

PMID- 9937228
TI  - Superconductivity of B1-MoN films annealed under high pressure.

PMID- 9937229
TI  - Changes in the nature of the Verwey transition in nonstoichiometric magnetite
      (Fe3O4).

PMID- 9937230
TI  - Commensurate-uniaxial-incommensurate transition of monolayer nitrogen on
      graphite.

PMID- 9937231
TI  - Monte Carlo study of reversible growth of clusters on a surface.

PMID- 9937232
TI  - Numerical solution for diffusion in periodic potentials: A comparison with the
      theory of activated processes.

PMID- 9937233
TI  - Erratum: Statics and dynamics of spin and electric dipoles in three, four, and
      other dimensions

PMID- 9937234
TI  - Observation of Cu NMR and spin canting in antiferromagnetic CuCl2

PMID- 9937235
TI  - Proposed determination of many-body effects in heavy-fermion systems by
      conduction-electron-spin resonance.

PMID- 9937236
TI  - 57Fe Mossbauer spectroscopy studies of the conducting poly(p-phenylene)-ferric
      chloride system.

PMID- 9937237
TI  - Tunneling alpha 2F( omega ) from sputtered thin-film NbN.

PMID- 9937238
TI  - Small normal-metal loop coupled to an electron reservoir.

PMID- 9937239
TI  - Direct observation of the peaked density of states in high-Tc A15 superconductors
      by electron energy-loss spectroscopy.

PMID- 9937240
TI  - Pressure increase of the electron-phonon interaction in superconducting hexagonal
      silicon.

PMID- 9937241
TI  - Second-sound generation in superfluids: Critically driven porous loudspeakers.

PMID- 9937242
TI  - Low-frequency Einstein mode in the heavy-fermion compound UBe13.

PMID- 9937243
TI  - Universality classes for critical wetting.

PMID- 9937244
TI  - Nucleation near the tricritical point of BaTiO3.

PMID- 9937245
TI  - Superelastic percolation networks and the viscosity of gels.

PMID- 9937246
TI  - Spinor exponents for the two-dimensional Potts model.

PMID- 9937247
TI  - Phase diagrams of the random-field Potts model in three dimensions.

PMID- 9937248
TI  - Paramagnetic neutron scattering and renormalization-group theory for isotropic
      ferromagnets at Tc.

PMID- 9937249
TI  - Generation of ultrasonic replica wave packets.

PMID- 9937250
TI  - Curved-wave-front corrections for photoelectron scattering.

PMID- 9937252
TI  - Angle-resolved photoemission investigation of the electronic structure of Be:
      Surface states.

PMID- 9937251
TI  - Small-atom approximations for photoelectron scattering in the intermediate-energy
      range.

PMID- 9937253
TI  - Linear magnetoresistance due to sample thickness variations: Applications to
      aluminum.

PMID- 9937255
TI  - Dynamical theory of Auger induced desorption.

PMID- 9937254
TI  - Density, Young's modulus, specific heat, and stability of icosahedral Al86Mn14.

PMID- 9937256
TI  - Possibility of observing quantum size effects in the electromagnetic absorption
      spectrum of small metal particles.

PMID- 9937257
TI  - Metal-insulator transition in the compensated sodium bronze, NaxTayW1-yO3.

PMID- 9937258
TI  - Collective multipole excitations in small metal particles: Critical angular
      momentum lcr for the existence of collective surface modes.

PMID- 9937260
TI  - Thermal conductivity and thermopower of vapor-grown graphite fibers.

PMID- 9937259
TI  - Empty electronic states at the (100), (110), and (111) surfaces of nickel,
      copper, and silver.

PMID- 9937261
TI  - Metal-nonmetal transition in tungsten bronzes: A photoemission study.

PMID- 9937263
TI  - Experimental and theoretical investigations of Cr(001) surface electronic
      structure.

PMID- 9937262
TI  - Photoemission study of the existence of a valence-band satellite in Fe.

PMID- 9937264
TI  - Extended x-ray-absorption fine-structure Einstein frequency and moments of the
      phonon spectrum: An experimental and theoretical study.

PMID- 9937265
TI  - Real-space convergence of the force series in the lattice dynamics of germanium.

PMID- 9937266
TI  - New stochastic treatment of fermions with application to a double-chain polymer.

PMID- 9937267
TI  - Electronic response function of coupled chains of finite radius.

PMID- 9937268
TI  - Orthogonality catastrophe and the x-ray photoemission spectrum.

PMID- 9937269
TI  - Band structures in one-dimensional binary alloys with self-similar atomic
      configurations.

PMID- 9937270
TI  - Physics of small metal clusters: Topology, magnetism, and electronic structure.

PMID- 9937271
TI  - Solute effect of Cu on interdiffusion in Al3Ti compound films.

PMID- 9937273
TI  - Importance of multiple forward scattering in medium- and high-energy electron
      emission and/or diffraction spectroscopies.

PMID- 9937272
TI  - Theory of classical diffusion jumps in solids.

PMID- 9937274
TI  - dc conductivity of strong and weak electron spin-orbit scattering materials near
      the metal-insulator transition.

PMID- 9937275
TI  - Benzene chemisorption on palladium surfaces. II. Resonance electron scattering
      and overtone vibrations.

PMID- 9937276
TI  - Total-energy differences and eigenvalue sums.

PMID- 9937277
TI  - Photoemission studies of ordered Pd overlayers on Au(111): Implications for CO
      chemisorption.

PMID- 9937278
TI  - Optical properties of well-defined granular metal systems.

PMID- 9937279
TI  - Numerical studies of the harmonic modes of a disordered zigzag chain.

PMID- 9937280
TI  - Orbital forces in the density-functional formalism: Application to the copper
      dimer.

PMID- 9937281
TI  - Electrical resistivity due to dislocations in highly purified copper.

PMID- 9937282
TI  - Effective two-body interaction in Coulomb Fermi liquids.

PMID- 9937283
TI  - One-hole excitation spectra of the one-dimensional Hubbard model.

PMID- 9937284
TI  - Ultrasonic relaxation from trapped hydrogen in rapidly cooled niobium.

PMID- 9937286
TI  - Superconducting fluctuations and magnetoconductance measurements of thin films in
      parallel magnetic fields.

PMID- 9937285
TI  - Inverse dielectric function of a bounded solid-state plasma.

PMID- 9937287
TI  - Pressure dependence of the electron-phonon interaction and Fermi-surface
      properties of Al, Au, bcc Li, Pb, and Pd.

PMID- 9937289
TI  - Symmetry criterion for surface states in solids.

PMID- 9937288
TI  - High-pressure structural investigation of cesium above 10 GPa.

PMID- 9937290
TI  - Experimental study of surface-enhanced second-harmonic generation on silver
      gratings.

PMID- 9937291
TI  - X-ray scattering studies of charge-density waves in tantalum disulfide.

PMID- 9937292
TI  - Stress-induced electric-dipole-allowed far-infrared generation at the spin
      resonance frequency in InSb.

PMID- 9937293
TI  - Integral formulation of transport equations: Quantum theory versus Boltzmann
      equation.

PMID- 9937295
TI  - Optimal basis sets for deep levels. II. Defect-molecule approximation.

PMID- 9937294
TI  - Optimal basis sets for deep levels. I. Potential representations and chemical
      trends.

PMID- 9937296
TI  - Band-gap renormalization in semiconductor quantum wells containing carriers.

PMID- 9937297
TI  - Optically detected magnetic resonance study of SiC:Ti.

PMID- 9937298
TI  - Low-temperature Peltier heat of an itinerant electron in a ferromagnetic
      semiconductor.

PMID- 9937299
TI  - Broken symmetry states for two-dimensional electrons in a strong magnetic field.

PMID- 9937300
TI  - Positron diffusion in Si.

PMID- 9937301
TI  - Ab initio relativistic pseudopotential study of the zero-temperature structural
      properties of SnTe and PbTe.

PMID- 9937302
TI  - Pressure and temperature dependences of the electronic conductivity of boron
      carbides.

PMID- 9937304
TI  - Angle-resolved photoemission studies of Ge(111)-c(2 x 8), Ge(111)-(1 x 1)H,
      Si(111)-(7 x 7), and Si(100)-(2 x 1).

PMID- 9937303
TI  - Electronic structure of semiconducting beta -NaSn.

PMID- 9937306
TI  - Exciton wave functions in semi-infinite semiconductors: A check of the adiabatic
      approximation.

PMID- 9937305
TI  - Determination of the Fermi surface in CdSnAs2 using a tight-binding model for
      chalcopyrites.

PMID- 9937307
TI  - Surface states and reconstruction on Ge(001).

PMID- 9937309
TI  - Restricted role of experiments in real space in determination of the Si(111)7 x 7
      reconstructed structure.

PMID- 9937308
TI  - Pyridine on cleaved Si(111): Analysis of the vibrational modes and nature of the
      chemisorption process.

PMID- 9937310
TI  - Density of impurity states associated with inversion layers.

PMID- 9937311
TI  - Electric field dependence of the binding energy of shallow donors in GaAs-Ga1
      xAlxAs quantum wells.

PMID- 9937312
TI  - Optical phonons in SnGeS3.

PMID- 9937313
TI  - Effect of free-carrier screening on the ultrafast relaxation kinetics in hot
      polar semiconductors.

PMID- 9937314
TI  - Time-differential perturbed-angular-correlation study of pure and Sn-doped In2O3
      semiconductors.

PMID- 9937315
TI  - Transient transport in amorphous solids: An exact calculation.

PMID- 9937317
TI  - Donor clusters in silicon. II. ESR simulations.

PMID- 9937316
TI  - Electron-hole plasma expansion in the direct-band-gap semiconductors CdS and
      CdSe.

PMID- 9937318
TI  - Quantitative piezospectroscopy of neutral copper in germanium.

PMID- 9937319
TI  - Highly accumulated electron layer at a semiconductor/electrolyte interface.

PMID- 9937320
TI  - Quantum theory of local perturbation of the charge-density wave by an impurity:
      Friedel oscillations.

PMID- 9937321
TI  - Reorientational motion in superionic sulfates: A Raman linewidth study.

PMID- 9937322
TI  - Electron bubbles, small-polaron holes, and charge-induced effects in solid
      deuterium.

PMID- 9937323
TI  - Molecular dynamics in crystalline alpha -nitrogen.

PMID- 9937324
TI  - Low-temperature specific heat of hydrogen-chemisorbed graphite-alkali-metal
      intercalation compounds.

PMID- 9937325
TI  - Creation of metastable states during sample preparation as demonstrated for
      silver mercury iodide.

PMID- 9937327
TI  - Helmholtz free energy of an anharmonic crystal to O( lambda 4). IV. Thermodynamic
      properties of Kr and Xe for the Lennard-Jones, Morse, and Rydberg potentials.

PMID- 9937326
TI  - Volume dependence of the Raman frequencies in ammonia solid I.

PMID- 9937328
TI  - Ionic bonding of transition-metal halides: A spectroscopic approach.

PMID- 9937329
TI  - ESR identification of radiation-induced oxygen vacancy centers in paratellurite.

PMID- 9937330
TI  - Cohesion and structure in stage-1 graphite intercalation compounds.

PMID- 9937332
TI  - Effect of exchange interactions on Gamma excitons in transition-metal halides.

PMID- 9937331
TI  - Theoretical study and assignment of absorption bands of dimer centers (Tl+)2 in
      KI.

PMID- 9937333
TI  - Phonon focusing in cubic crystals.

PMID- 9937334
TI  - Energy spectrum of the bound polaron.

PMID- 9937335
TI  - Contribution of the Jahn-Teller effect in the electronic Raman scattering in
      MgO:Co2+

PMID- 9937336
TI  - Concentration-dependent donor energies and Mott constant in heavily doped n-type
      silicon.

PMID- 9937337
TI  - Possibility of an excitonic ground state in quantum wells.

PMID- 9937339
TI  - Quasireciprocal relation between the Cs IV and beta -Sn structures.

PMID- 9937338
TI  - Thermoreflectance investigation of zirconium hydrides in the face-centered
      tetragonal phase.

PMID- 9937340
TI  - Higher-order fractional quantum Hall effect.

PMID- 9937341
TI  - Size effect in NbSe3: Length dependence of the threshold field.

PMID- 9937342
TI  - Compton-profile anisotropies in graphite and hexagonal boron nitride.

PMID- 9937344
TI  - Burstein shift of the contact exciton.

PMID- 9937343
TI  - Size effects in metallic thin films.

PMID- 9937346
TI  - Dilute instanton gas as the precursor to the integral quantum Hall effect.

PMID- 9937345
TI  - Migration and activation defect volumes in CdF2.

PMID- 9937348
TI  - Comment on "Electron mobility in modulation-doped heterostructures"

PMID- 9937347
TI  - Quenching of a surface state on W(100) by adsorption of Au.

PMID- 9937349
TI  - Response to "Comment on 'Electron mobility in modulation-doped heterostructures'
      "

PMID- 9937350
TI  - Relation between Gruneisen constants and nonlinearity parameters.

PMID- 9937351
TI  - Model of the metastable center in indium antimonide: Comment on "Pressure
      dependent compensation in InSb"

PMID- 9937352
TI  - Erratum: Thomas-Fermi-Dirac statistical theory of dispersive dielectric screening
      in undoped semiconductors at zero temperature

PMID- 9937353
TI  - Erratum: Soluble models of rate processes in periodic systems with many degrees
      of freedom

PMID- 9937354
TI  - Upper bound to the polaron ground state in a magnetic field using the Feynman
      path-integral method.

PMID- 9937355
TI  - UAl2: Fine structure of the f bands.

PMID- 9937356
TI  - Observation of a large ground-state splitting in the infrared absorption spectrum
      of Zn in Ge.

PMID- 9937357
TI  - Oxidation behavior and segregation of uranium in the intermetallic compound UFe

PMID- 9937358
TI  - Kinetic energy of an electron gas.

PMID- 9937359
TI  - Vibrational line shape of chemisorbed CO.

PMID- 9937360
TI  - One-dimensional density of states and the phase of the transmission amplitude.

PMID- 9937362
TI  - Charge-density waves with electron-electron interactions.

PMID- 9937361
TI  - Surface-barrier structure of Cu(001) from analysis of low-energy electron
      diffraction.

PMID- 9937363
TI  - Model for phonon-assisted indirect recombination at impurity sites in
      semiconductors: A test of impurity wave-function theories.

PMID- 9937364
TI  - Structural and chemical changes in binary versus ternary tetrahedral
      semiconductors.

PMID- 9937365
TI  - High-resolution electron energy loss as a probe of the Si-Al Schottky-barrier
      formation process.

PMID- 9937366
TI  - Direct measurement of the density of states of a two-dimensional electron gas.

PMID- 9937368
TI  - Continuum theory for defect vibrations in conjugated polymers.

PMID- 9937367
TI  - Optical transitions at confined resonances in (001) GaAs-Ga1-xAlxAs
      superlattices.

PMID- 9937369
TI  - Droplet wave functions for the fractional quantum Hall effect.

PMID- 9937370
TI  - Electric field dependence of the Raman phonon in the charge-density-wave state of
      TaS3.

PMID- 9937371
TI  - Angle-resolved ultraviolet-photoelectron-spectroscopy study of the Si(111) sqrt 3
      bar x sqrt 3-bar-Al surface.

PMID- 9937373
TI  - Dipole-dipole-interaction-induced line narrowing in thin-film vibrational-mode
      spectra.

PMID- 9937374
TI  - Total transformation of electronic F-center emission into multiple-state CN-
      vibrational emission (4.8 microm) in CsCl.

PMID- 9937372
TI  - Nature of Ce 4f electronic states from 4d excitations in metals and insulators.

PMID- 9937375
TI  - Pressure-induced structural transformations in Bi-doped amorphous germanium
      sulfide.

PMID- 9937376
TI  - Quantum chemical assessment of the possibility of soliton switching.

PMID- 9937377
TI  - Relaxation of H nuclear spins via H2 molecules.

PMID- 9937378
TI  - Mossbauer-effect investigation of a Cr-13.5 at. % Fe alloy doped with 0.7 at. %
      119Sn.

PMID- 9937379
TI  - Dependence of atom ejection on electronic energy loss.

PMID- 9937380
TI  - Dynamic behavior of ESR and NMR fine-structure spectra under orientational
      diffusion motion in polycrystalline-amorphous condensed matter.

PMID- 9937381
TI  - Proportionality between ion-beam-induced epitaxial regrowth in silicon and
      nuclear energy deposition.

PMID- 9937382
TI  - Inelastic neutron scattering in amorphous Fe0.78P0.22 and crystalline Fe3P
      systems.

PMID- 9937384
TI  - Spectroscopic properties of alexandrite crystals.

PMID- 9937383
TI  - High-field 19F NMR relaxation studies in the superionic conductor Mn:PbF2.

PMID- 9937385
TI  - Interpretation of NMR diffusion measurements in uniform- and nonuniform-field
      profiles.

PMID- 9937386
TI  - Elastic and inelastic scattering of electrons reflected from solids: Effects on
      energy spectra.

PMID- 9937387
TI  - ESR study of two phases of di

PMID- 9937389
TI  - Enhancement of energy loss of fast electrons in a ferroelectric medium near the
      Curie temperature.

PMID- 9937388
TI  - Spin-flip electron-energy-loss spectroscopy in itinerant-electron ferromagnets:
      Collective modes versus Stoner excitations.

PMID- 9937390
TI  - Crystal-field analysis of PbMoO4:Pr3+

PMID- 9937391
TI  - Anomalous behavior of the Mossbauer resonance width in mixed-valence EuNi2P2.

PMID- 9937392
TI  - Pressure dependence of low-frequency zero-sound propagation in superfluid 3He-A
      and -A1.

PMID- 9937393
TI  - 4He ordering transition on single-leaf pyrolytic graphite: A microcalorimetry
      study.

PMID- 9937394
TI  - 3He flow in dilute 3He-4He mixtures at temperatures between 10 and 150 mK.

PMID- 9937396
TI  - Tunneling alpha 2F( omega ) as a function of composition in A15 V-Si.

PMID- 9937395
TI  - Crucial role of residual gases in amorphization of crystalline films.

PMID- 9937397
TI  - Superconducting critical temperature Tc and electronic structure of pseudoternary
      Y(Rh1-xRux

PMID- 9937399
TI  - ac losses in type-II superconductors in parallel magnetic fields.

PMID- 9937398
TI  - Time-dependent magnetic structures of the superconducting mixed ternary system
      Ho(Rh1-xIrx

PMID- 9937400
TI  - Quasiparticle motion in superfluid 3He and Kapitza resistance of 3He A-B phase
      boundary.

PMID- 9937402
TI  - Symmetry properties of triplet superconductors.

PMID- 9937401
TI  - Properties of superconducting vanadium nitride sputtered films.

PMID- 9937404
TI  - Variational Monte Carlo study of heavy-atom impurities in liquid 4He.

PMID- 9937403
TI  - Ground-state properties of spin-aligned deuterium.

PMID- 9937405
TI  - Superfluid current in 3He-A at T=0. II.

PMID- 9937406
TI  - Time-dependent Ginzburg-Landau equations for a dirty gapless superconductor.

PMID- 9937407
TI  - Thermodynamics of anisotropic superconducting indium analyzed in terms of
      Eliashberg theory.

PMID- 9937409
TI  - Theory and feasibility of using low-energy electron diffraction to study specific
      heat anomalies at surface phase transitions.

PMID- 9937408
TI  - Structural phase transition and superconducting properties of Th3P4-type La
      chalcogenides.

PMID- 9937411
TI  - Impurity effect on the singularity of the local magnetization in the spin-1/2 XY
      chain.

PMID- 9937410
TI  - Phase diagram of LixMo

PMID- 9937412
TI  - New spin-fluctuation system: U0.5Th0.5Al3.

PMID- 9937413
TI  - Impurity effects on domain-growth kinetics. I. Ising model.

PMID- 9937414
TI  - Impurity effects on domain-growth kinetics. II. Potts model.

PMID- 9937416
TI  - Finite-size scaling study of the two-dimensional Ising spin glass.

PMID- 9937415
TI  - Effect of low-temperature ion irradiation on the spin glass CuMn.

PMID- 9937417
TI  - Finite-temperature magnetism of disordered Fe-V alloys.

PMID- 9937418
TI  - Crystal-field transitions in f-electron oxides.

PMID- 9937419
TI  - Numerical simulation of quantum spin models.

PMID- 9937421
TI  - Classical sine-Gordon limit of Bethe-ansatz thermodynamics.

PMID- 9937420
TI  - Hyperfine tails and exchange-field distributions in amorphous magnetic spin
      glasses.

PMID- 9937423
TI  - New renormalization equations for the Kosterlitz-Thouless transition.

PMID- 9937422
TI  - Two-dimensional XY model in a random uniaxial field.

PMID- 9937424
TI  - Neutron diffraction study of magnetically ordered Tm2Fe3Si5.

PMID- 9937426
TI  - Monte Carlo renormalization-group study of the impure Baxter-Wu model.

PMID- 9937425
TI  - Iron d-band occupancy in amorphous FexGe1-x.

PMID- 9937427
TI  - Rotary modes in the antifluorite crystal (ND4)2SnCl6.

PMID- 9937428
TI  - Ground-state alternation and excitation energy of S=(1/2) linear Heisenberg
      antiferromagnets.

PMID- 9937430
TI  - Role of potential-energy scaling in the low-temperature relaxation behavior of
      amorphous materials.

PMID- 9937429
TI  - Phase transition of CsAu at high pressure.

PMID- 9937431
TI  - Zero-field susceptibility of finite-size Kosterlitz-Thouless systems.

PMID- 9937432
TI  - Lennard-Jones molecules on a two-dimensional lattice: A model anisotropic XY
      system.

PMID- 9937433
TI  - Applicability of the sine-Gordon model to the magnetic heat capacity of
      (C6H11NH3)CuBr3.

PMID- 9937435
TI  - Magnon-mass renormalization in (CH3)4NMnCl

PMID- 9937434
TI  - Optical absorption spectra of the one-dimensional antiferromagnets: Exciton
      magnon transition and double excitation in CsNiBr3.

PMID- 9937436
TI  - Applicability of mean-field theory to wetting in binary-liquid mixtures.

PMID- 9937437
TI  - Two-dimensional XY model with multiple symmetry-breaking fields.

PMID- 9937438
TI  - Surface tension and stress in solids: The rigid-planes model.

PMID- 9937440
TI  - Theory of phase transitions and modulated structures in ferroelectrics.

PMID- 9937439
TI  - Dilute random-field Ising models and uniform-field antiferromagnets.

PMID- 9937441
TI  - X-band antiferromagnetic resonance measurements in KNiF3.

PMID- 9937442
TI  - Thermal conductivity of amorphous ferromagnets.

PMID- 9937443
TI  - Analytical and numerical studies of the easy-plane antiferromagnetic chain:
      Application to (CH3)4NMnCl3.

PMID- 9937445
TI  - Rotational dynamics of molecular impurities in alkali halide crystals.

PMID- 9937444
TI  - Spin-wave excitations and perpendicular susceptibility of a diluted
      antiferromagnet near percolation threshold.

PMID- 9937446
TI  - Low-temperature spin-wave excitations in nickel, by neutron triple-axis
      spectroscopy.

PMID- 9937447
TI  - Hyperfine fields at sp sites in the Heusler alloys Rb2MnZ (Z=Ge,Sn,Pb).

PMID- 9937448
TI  - Effect of orbit-lattice interaction in Mossbauer studies: Quadrupole splitting of
      57Fe2+ in FeCO3.

PMID- 9937450
TI  - Extraction of the condensate fraction from the momentum distribution in
      superfluid 4He.

PMID- 9937449
TI  - Effect of finite mean free path on spin-flip scattering rates near the critical
      point of magnetically ordered systems.

PMID- 9937451
TI  - Electronic density of states at the surface of a superconductor in contact with a
      magnetic insulator.

PMID- 9937452
TI  - p-wave superconductivity in heavy-fermion systems: An induced-interaction
      approach.

PMID- 9937453
TI  - Polaronic behavior of electrons on a liquid-helium film.

PMID- 9937454
TI  - Critical behavior of the quantum double-sine-Gordon model.

PMID- 9937455
TI  - Nonuniversal critical exponents for transport in percolating systems with a
      distribution of bond strengths.

PMID- 9937456
TI  - Neutron scattering measurements of phonons in iron above and below Tc.

PMID- 9937457
TI  - Heat capacity and the wetting transition in multilayer films.

PMID- 9937458
TI  - Entropy of the intercalation compound LixMo6Se8 from calorimetry of
      electrochemical cells.

PMID- 9937459
TI  - Breakdown of replica analyticity in the one-dimensional axis model.

PMID- 9937460
TI  - Simple renormalization-group method for calculating geometrical equations of
      state.

PMID- 9937461
TI  - Comment on "Magnetic properties of a glassy ferromagnet: Fe78B13Si9"

PMID- 9937462
TI  - Comment on "Generalized Curie-Weiss Law"

PMID- 9937463
TI  - Effect of crystal fields and itinerant-electron polarization on the magnetic
      susceptibilities of rare-earth rhodium borides.

PMID- 9937465
TI  - Resistance scaling function for two-dimensional superconductors and Monte Carlo
      vortex-fluctuation simulations.

PMID- 9937464
TI  - Anomalous electron magnetic resonance in p-wave superconductors with strong spin
      orbit coupling.

PMID- 9937466
TI  - Pair distributions and energy-density functionals for liquid 4He drops.

PMID- 9937467
TI  - Quantum diffusion in thin disordered wires.

PMID- 9937468
TI  - Temperature dependence of quantum decay rates in dissipative systems.

PMID- 9937470
TI  - Critical dynamics, Lifshitz tricriticality, and supersymmetry: The Ising model on
      the hcp lattice.

PMID- 9937469
TI  - Angular relation and energy dependence of Andreev reflection.

PMID- 9937472
TI  - Diffusion in a medium with connected traps.

PMID- 9937471
TI  - Novel Lifshitz tricritical point and critical dynamics.

PMID- 9937473
TI  - Examination of the necessity of complete wetting near critical points in systems
      with long-range forces.

PMID- 9937474
TI  - Anomalous trapping: Effect of interaction between diffusing particles.

PMID- 9937476
TI  - N processes, the relaxation-time approximation, and lattice thermal conductivity.

PMID- 9937475
TI  - Infrared-photoinduced-absorption studies in soluble trans-polyacetylene.

PMID- 9937477
TI  - Equation of state and properties of lithium.

PMID- 9937478
TI  - Structural relaxation of amorphous Pd82Si18: X-ray measurements, electrical
      resistivity measurements, and a comparison using the Ziman theory.

PMID- 9937479
TI  - Application of the embedded-atom method to liquid transition metals.

PMID- 9937480
TI  - Alloy broadening of impurity electronic spectra: One-dimensional-model
      calculations for a ternary alloy.

PMID- 9937481
TI  - 4f-5d hybridization and the alpha - gamma phase transition in cerium.

PMID- 9937482
TI  - Multiple-scattering theories including correlation effects to obtain the
      effective dielectric constant of nonhomogeneous thin films.

PMID- 9937483
TI  - Physical content of the orthogonalized final-state rule of Davis and Feldkamp.

PMID- 9937484
TI  - Investigation of multilayer relaxation on Al(110) with the use of self-consistent
      total-energy calculations.

PMID- 9937486
TI  - Applications of the effective-medium approximation to cubic geometries.

PMID- 9937485
TI  - Unoccupied bulk and surface states on Ag(111) studied by inverse photoemission.

PMID- 9937487
TI  - Coverage dependence and isotope effect in quantum surface diffusion.

PMID- 9937488
TI  - High-resolution angle-resolved photoemission study of the Ag band structure along
      Lambda.

PMID- 9937489
TI  - Angle-resolved photoemission studies of oxygen adsorbed on Fe(100).

PMID- 9937490
TI  - Atom-surface interaction: Zero-point energy formalism.

PMID- 9937491
TI  - Measurement of the Ruderman-Kittel interaction in tungsten.

PMID- 9937492
TI  - Infrared-laser-induced photodesorption of NH3 and ND3 adsorbed on single-crystal
      Cu(100) and Ag film.

PMID- 9937493
TI  - Interaction energy between a positronium atom and a metal surface.

PMID- 9937494
TI  - Plasmon structure in the appearance-potential spectroscopy of metals.

PMID- 9937496
TI  - Multiband effects in weak localization.

PMID- 9937495
TI  - Acoustical polaron in three dimensions: The ground-state energy and the self
      trapping transition.

PMID- 9937497
TI  - Evidence for 6d valence states in alpha -U, UGa2, and UGa3 as revealed by
      resonant photoemission.

PMID- 9937498
TI  - Cluster-method study of surface effects in fcc binary alloys.

PMID- 9937499
TI  - Thermal disorder in Pt and Ir metal: Comparison of model and experimental
      extended x-ray-absorption fine structure.

PMID- 9937500
TI  - Phase analysis of image states and surface states associated with nearly-free
      electron band gaps.

PMID- 9937501
TI  - Dynamic structure factor S(k, omega ) of beryllium by x-ray inelastic scattering
      experiments.

PMID- 9937502
TI  - Electronic interactions in metal-hydrogen solid solutions: ScHx, YHx, and
      V0.75Nb0.25Hx.

PMID- 9937503
TI  - Energy bands and final-state effects in K0.30MoO3.

PMID- 9937504
TI  - Statistical model for the trapping of interstitials by substitutional
      (interstitial) atoms in solids.

PMID- 9937505
TI  - Effect of an oxide layer on the far-infrared absorption of small silver
      particles.

PMID- 9937507
TI  - Studies of total density of states of metals up to 70 eV above EF.

PMID- 9937506
TI  - Brownian motion and vibrational phase relaxation at surfaces: CO on Ni(111).

PMID- 9937509
TI  - Interaction between surface plasmons and localized plasmons.

PMID- 9937508
TI  - Tracer diffusion at the percolation threshold.

PMID- 9937510
TI  - Quantum Hall conductances and localization in a magnetic field.

PMID- 9937511
TI  - Spontaneous emission by two atoms with different resonance frequencies near a
      metal surface.

PMID- 9937512
TI  - Surface-enhanced second-harmonic generation at a silver grating: A numerical
      study.

PMID- 9937513
TI  - Localization as a breakdown of extended states.

PMID- 9937514
TI  - Autoionization and Auger features of clean and oxygen-exposed surfaces of Fe, Co
      and Ni.

PMID- 9937515
TI  - Electronic structure of amorphous Si0.8Al0.2.

PMID- 9937517
TI  - Intermediate valence in TmxY1-xSe using MV x-ray absorption spectroscopy.

PMID- 9937516
TI  - Time- and angle-resolved photoemission study of InP(110).

PMID- 9937518
TI  - Configurationally bistable C center in quenched Si:B: Possibility of a boron
      vacancy pair.

PMID- 9937519
TI  - Semiconductor pseudobinary alloys: Bond-length relaxation and mixing enthalpies.

PMID- 9937520
TI  - Subbands and Landau levels in the two-dimensional hole gas at the GaAs-AlxGa1-xAs
      interface.

PMID- 9937521
TI  - Direct evidence for the acceptorlike character of the Cu-related C and F bound
      exciton centers in GaAs.

PMID- 9937522
TI  - Novel recombination mechanism for interacting bound-exciton complexes in Cu-doped
      ZnTe.

PMID- 9937523
TI  - Electronic structure of RuS2.

PMID- 9937524
TI  - Thermally activated exciton transfer in GaAs1-xPx

PMID- 9937525
TI  - Interfacial chemistry and Schottky-barrier formation of the Ni/InP(110) and
      Ni/GaAs(110) interfaces.

PMID- 9937526
TI  - Theory of excitons in semiconductor quantum wells containing degenerate electrons
      or holes.

PMID- 9937527
TI  - Theory of impurity-band conduction in silicon inversion layers in high magnetic
      fields.

PMID- 9937529
TI  - Stresses in semiconductors: Ab initio calculations on Si, Ge, and GaAs.

PMID- 9937528
TI  - Quantum-mechanical theory of stress and force.

PMID- 9937530
TI  - Photoluminescence determination of well depth of Ga

PMID- 9937531
TI  - Ellipsometric studies of the dielectric function of Cd1-xMnxTe alloys.

PMID- 9937532
TI  - Observation of clustered molecules and ions in liquid iodine.

PMID- 9937533
TI  - Theory of dispersion instabilities associated with surface electromagnetic waves
      in layered semiconductor media.

PMID- 9937535
TI  - Optical properties of complex defects created by Ag diffusion in ZnTe.

PMID- 9937534
TI  - Numerical solutions to the rate equations governing the simultaneous release of
      electrons and holes during thermoluminescence and isothermal decay.

PMID- 9937536
TI  - Low-temperature optical absorption in AlxGa1-xAs grown by molecular-beam epitaxy.

PMID- 9937537
TI  - Nonrectangular quantum wells as a basis for studying the band offsets at GaAs-Ga1
      xAlx As interfaces.

PMID- 9937538
TI  - Theoretical study of subband levels in semiconductor heterostructures.

PMID- 9937539
TI  - Exchange and correlation in density-functional theory.

PMID- 9937540
TI  - Density-functional theory of the band gap.

PMID- 9937541
TI  - Calculation of the Kohn-Sham potential and its discontinuity for a model
      semiconductor.

PMID- 9937542
TI  - Kinetics of the bound magnetic polaron and the decay rate of thermodynamic
      fluctuation.

PMID- 9937543
TI  - Composition and electronic properties of P-enriched InP (1-bar 1-bar 1-bar)-Au
      interfaces.

PMID- 9937545
TI  - Spin-dependent scattering of conduction electrons in diluted magnetic
      semiconductors: Hg

PMID- 9937544
TI  - Transient conductivity and photoconductivity in a-Si:H.

PMID- 9937546
TI  - Effect of hydrostatic pressure, temperature, and doping on self-diffusion in
      germanium.

PMID- 9937547
TI  - Observation of anticrossing between Zeeman-split 1s(T2) states of opposite spin
      for As donors in germanium.

PMID- 9937548
TI  - Time-resolved photoluminescence spectra of Gax

PMID- 9937549
TI  - Interface potential changes and Schottky barriers.

PMID- 9937550
TI  - Neutral (Cu-Li) complexes in GaP: The (Cu-Li)III bound exciton at 2.242 eV.

PMID- 9937551
TI  - Resonance Raman scattering in InSb: Deformation potentials and interference
      effects at the E1 gap.

PMID- 9937552
TI  - Polytope model and the electronic and structural properties of amorphous
      semiconductors.

PMID- 9937554
TI  - Effective deactivation of the ZnS visible photoluminescence by iron impurities.

PMID- 9937553
TI  - Model calculation of local-field corrections to the static dielectric properties
      of a covalent semiconductor.

PMID- 9937555
TI  - Conductivity, plasmon, and cyclotron-resonance anomalies in Si(100) metal-oxide
      semiconductor systems.

PMID- 9937556
TI  - New variational solution for the lowest subband level of the two-dimensional
      electron gas.

PMID- 9937557
TI  - Predicted energy band gaps of (AIIIBV)1-xX2xIV metastable, substitutional,
      crystalline alloys.

PMID- 9937558
TI  - Excitons and polaritons in InP.

PMID- 9937559
TI  - Analysis of thermally stimulated currents in amorphous silicon.

PMID- 9937561
TI  - High-pressure phase transitions in CaTe and SrTe.

PMID- 9937560
TI  - Three-dimensional effects in trans-polyacetylene.

PMID- 9937562
TI  - Effect of an Al interlayer on the GaAs/Ge(100) heterojunction formation.

PMID- 9937563
TI  - Quasiparticle band structure of lithium hydride.

PMID- 9937564
TI  - Effect of impurities on the dielectric response of the charge-density wave in
      K0.3MoO3.

PMID- 9937565
TI  - Calculated properties of solid O2 under pressure at low temperature.

PMID- 9937566
TI  - Treatment of the relaxed F center in KCl with the recursion method.

PMID- 9937567
TI  - Frequency-dependent optical dephasing and the nature of inhomogeneous broadening
      in crystals.

PMID- 9937569
TI  - Quasielastic light scattering in superionic beta -alumina.

PMID- 9937568
TI  - Pressure-tuning resonance between the vibron and the libron in CH

PMID- 9937571
TI  - Relaxation of the rocksalt (001) surface: Alkali halides, MgO, and PbS.

PMID- 9937570
TI  - Temperature dependence of the electrical resistivities in AlCl3-graphite
      intercalation compounds determined by conduction-carrier spin resonance.

PMID- 9937572
TI  - Cr+ and Cr3+ defects in CaF2 and SrF2.

PMID- 9937574
TI  - Optical properties of coevaporated AgSiOx cermet films.

PMID- 9937573
TI  - Molecular disorder in even-numbered paraffins.

PMID- 9937575
TI  - Fermion-propagator calculations of excitations in polyenes with the use of a
      Heisenberg (XYZ) Hamiltonian. I. Formalism and parametrization.

PMID- 9937576
TI  - Fermion-propagator calculations of excitations in polyenes with the use of a
      Heisenberg (XYZ) Hamiltonian. II. Applications to large systems.

PMID- 9937577
TI  - Surface-plasmon excitation on oxide-covered spherical particles.

PMID- 9937578
TI  - Screened ion-ion interaction in mercury-chain compounds: Single chain.

PMID- 9937579
TI  - Fast method for calculating the self-consistent electronic structure of random
      alloys. II. Optimal use of the complex plane.

PMID- 9937581
TI  - Isostructural electronic anomaly in La and La-Th alloys at high pressures.

PMID- 9937580
TI  - Orthogonalized-moments method.

PMID- 9937582
TI  - Luminescence excitation spectroscopy on Ga0.47In0.53As/ Al0.48In0.52As quantum
      well heterostructures.

PMID- 9937584
TI  - Possible mechanism for thermal conductivity in (KBr)1-x(KCN)x.

PMID- 9937583
TI  - Temperature dependence of the dc ionic conductivity of beta -AgI and AgCrS2.

PMID- 9937585
TI  - Free energy of surface segregation in binary alloys.

PMID- 9937586
TI  - Electron-energy-loss x-ray absorption spectroscopy: A nonde- structive structural
      depth microprobe.

PMID- 9937587
TI  - Force between jellium films at small separation in the linearized Thomas-Fermi
      approximation.

PMID- 9937588
TI  - Raman spectra and electron-phonon coupling in poly(p-phenylene).

PMID- 9937590
TI  - Erratum: Photoelastic constants of calcite from its first-order raman spectrum

PMID- 9937589
TI  - Comment on "Analysis of the stoichiometry and temperature dependence of cation
      diffusion in wustite, Fe1- delta O.

PMID- 9937591
TI  - Erratum: White lines at K edges of light atoms

PMID- 9937593
TI  - Quantitative characterization of abrupt interfaces by angle-resolved Auger
      electron emission.

PMID- 9937594
TI  - Precise molecular orientation determination for adsorbates using x-ray
      photoelectron diffraction: Methoxy (CH3O) and CO on Cu(110).

PMID- 9937592
TI  - Hybridization between 4f and conduction electrons and saturation of mixed valence
      in cerium-based systems.

PMID- 9937596
TI  - Stress-induced hydrogen reorientation in a bcc Nb-50-at. %-V alloy.

PMID- 9937595
TI  - Postannealing of coldly condensed Ag films: Influence of pyridine preadsorption.

PMID- 9937597
TI  - Anomalies in the low-temperature thermal and electrical resistivities of copper.

PMID- 9937598
TI  - Dispersion of surface phonons in xenon overlayers physisorbed on the Ag(111)
      surface.

PMID- 9937599
TI  - Metastability of the midgap level EL2 in GaAs: Relationship with the As antisite
      defect.

PMID- 9937600
TI  - Competition between neighboring minima in the fractional quantum Hall effect.

PMID- 9937601
TI  - Inelastic electron scattering by collective charge-density excitations at the
      surface of a semiconductor superlattice.

PMID- 9937602
TI  - Direct experimental observation of two-dimensional shrinkage of the exciton wave
      function in quantum wells.

PMID- 9937603
TI  - Design of novel polymers with metallic conductivity: Polyazacetylene and
      polyboracetylene.

PMID- 9937604
TI  - Effects of uniaxial stress on the electronic and optical properties of GaAs
      AlxGa1-xAs quantum wells.

PMID- 9937605
TI  - Planar versus helical cis-polyacetylene.

PMID- 9937606
TI  - Evolution of the Pt conduction band in a solid Xe layer.

PMID- 9937607
TI  - X-ray-absorption near-edge structure of 3d transition elements in tetrahedral
      coordination: The effect of bond-length variation.

PMID- 9937608
TI  - 2 pi affinity level of adsorbed CO: Bonding and dispersion.

PMID- 9937609
TI  - Extraction of phonon density of states from optical spectra.

PMID- 9937610
TI  - Positron-lifetime studies of physisorbed nitrogen and argon surfaces.

PMID- 9937612
TI  - Vacancy recovery and vacancy-hydrogen interaction in niobium and tantalum studied
      by positrons.

PMID- 9937611
TI  - Nuclear relaxation of dilute Cd dopants in liquid semiconducting SexTe1-x alloys.

PMID- 9937613
TI  - Ultrasonic studies of radiation damage in an aluminum-manganese alloy.

PMID- 9937614
TI  - Cluster-ion formation in pulsed-laser-stimulated field desorption of condensed
      materials.

PMID- 9937615
TI  - Radiation from fast charged particles in crystals: Unified quantal treatment.

PMID- 9937616
TI  - Correlation effects in dynamical charge-transfer processes.

PMID- 9937618
TI  - Third-sound propagation on a periodic substrate.

PMID- 9937617
TI  - Upper critical field of strongly disordered three-dimensional superconductors:
      Localization effects.

PMID- 9937619
TI  - Effect of oxygen impurities on properties of the ternary superconductor SnMo6S8:
      Extended x-ray-absorption fine-structure determination of bond distances and
      local-density cluster calculations.

PMID- 9937620
TI  - Bosonization of a two-level system with dissipation.

PMID- 9937621
TI  - Phonon anomalies and local atomic displacements in the exchange-enhanced
      superconductor U6Fe.

PMID- 9937622
TI  - Depression of the superconducting transition temperature of the Heusler alloy
      Pd2YSn with the addition of magnetic rare-earth metals.

PMID- 9937624
TI  - Dynamic structure factors and neutron scattering spectra of liquid 3He-4He
      mixtures.

PMID- 9937623
TI  - Electron-phonon coupling of the actinide metals.

PMID- 9937625
TI  - Dissipative quantum tunneling at finite temperatures.

PMID- 9937626
TI  - Quantum shot noise in tunnel junctions.

PMID- 9937628
TI  - Quasiclassical approximation to final-state effects in the scattering of neutrons
      from a hard-core fluid.

PMID- 9937627
TI  - Dynamics of simple dissipative systems.

PMID- 9937629
TI  - Ground-state energy of jellium.

PMID- 9937630
TI  - Shock determination of the Gruneisen parameter for lanthanum and the 6s-5d
      transition.

PMID- 9937631
TI  - Density of states for random-central-force elastic networks.

PMID- 9937632
TI  - Magnetization and specific heat of the isoelectronic pseudobinary compounds PrAg1
      xCux.

PMID- 9937633
TI  - Spin-correlation function in the two-dimensional XY model.

PMID- 9937634
TI  - Finite-temperature properties of the damped one-dimensional quantum sine-Gordon
      model.

PMID- 9937635
TI  - Dipolar relaxation and limit of ergodicity in K1-xLixTaO3.

PMID- 9937636
TI  - Roughening transition temperature in the presence of an adsorbing fluid.

PMID- 9937637
TI  - Dynamics of proton spin-lattice relaxation in glycerol.

PMID- 9937638
TI  - Instability, spinodal decomposition, and nucleation in a system with continuous
      symmetry.

PMID- 9937639
TI  - Localization properties of random and partially ordered one-dimensional systems.

PMID- 9937640
TI  - Low-temperature specific heat of uranium monopnictides and monochalcogenides.

PMID- 9937641
TI  - Order in metallic glasses and icosahedral crystals.

PMID- 9937643
TI  - Finite-size effects in the spherical model of ferromagnetism: Antiperiodic
      boundary conditions.

PMID- 9937642
TI  - Behavior of depleted elastic networks: Comparison of effective-medium and
      numerical calculations.

PMID- 9937645
TI  - Damping of charge-density-wave motion.

PMID- 9937644
TI  - Temperature dependence of the magnetic susceptibility of CoCl2-graphite
      intercalation compounds.

PMID- 9937646
TI  - Two-dimensional ordering of chlorine on Ag(100).

PMID- 9937647
TI  - Pinning of incommensurate spin-density waves by impurities.

PMID- 9937648
TI  - Sequential deposition and metastable states in rare-earth/Co films.

PMID- 9937649
TI  - Hysteretic behavior of the site-diluted Ising antiferromagnet in uniform applied
      fields.

PMID- 9937651
TI  - Configurational elastic energy in beta -brass.

PMID- 9937650
TI  - Wetting of a disordered substrate.

PMID- 9937652
TI  - Magnetic specific heat and structural phase transitions in (CH3)4NMnCl3 (TMMC)
      and TMMC:Cu2+ studied by crystal optics.

PMID- 9937653
TI  - Spin chains in a field: Crossover from quantum to classical behavior.

PMID- 9937654
TI  - Equation of state for the infinite cluster and backbone in the anisotropic square
      lattice.

PMID- 9937655
TI  - Thermally desorbed positronium from a clean and oxygen-covered Mo(110) surface.

PMID- 9937656
TI  - Slow orientational-motional correlation-time measurements for anisotropic NMR
      centers in polycrystalline-amorphous condensed matter.

PMID- 9937658
TI  - Magnetism and superconductivity in the system Ce1-xLaxRh3B2.

PMID- 9937657
TI  - EPR of Gd3+-doped single crystals of LiYF4 and LiYbF4: Gd3+-Yb3+ exchange
      constant.

PMID- 9937660
TI  - Reduced quantum fluctuations in the Josephson junction.

PMID- 9937659
TI  - Criterion for the observability of macroscopic quantum coherence.

PMID- 9937661
TI  - Spectral dimension of elastic Sierpinski gaskets with general elastic forces.

PMID- 9937663
TI  - Two-dimensional critical points and critical isotherms.

PMID- 9937662
TI  - Determination of multicritcal points for lattice-gas models by finite-size
      scaling of the susceptibility.

PMID- 9937664
TI  - Coefficients to O( epsilon 3) for the mixed fixed point of the nm-component field
      model.

PMID- 9937665
TI  - Renormalization of a nonuniversal wetting exponent.

PMID- 9937666
TI  - Linear temperature dependence of susceptibility of UAl2 between 3 and 10 K.

PMID- 9937667
TI  - Gap of S=1/2 alternating antiferromagnetic Heisenberg chains at T=0 K.

PMID- 9937668
TI  - Phase transition in AlCl3-graphite as seen by the thermal hysteresis in the
      conduction-carrier spin resonance.

PMID- 9937669
TI  - Comment on "Frustration effects in the disordered system CsMnFeF6, studied by
      neutron scattering, ac susceptibility, and magnetization measurements"

PMID- 9937670
TI  - Reply to "Comment on 'Frustrated effects in the disordered system CsMnFeF6,
      studied by neutron scattering, ac susceptibility, and magnetization measurements'
      "

PMID- 9937672
TI  - Erratum: Effect of zero-point fluctuations on the long-range phase coherence of
      granular films

PMID- 9937671
TI  - Comment on "Symmetry and structure of quantized vortices in superfluid 3He-B"

PMID- 9937673
TI  - Antiferromagnetic restricted solid-on-solid model: Ising models on rough
      surfaces.

PMID- 9937674
TI  - Temperature dependence of the normal-metal Aharonov-Bohm effect.

PMID- 9937675
TI  - Effect of superconducting electrons on the energy splitting of tunneling systems.

PMID- 9937676
TI  - Low-frequency boundary of the strongly chaotic regime of an rf-driven Josephson
      junction.

PMID- 9937677
TI  - Epitaxial growth and superconducting-transition-temperature anomalies of Mo/V
      superlattices.

PMID- 9937678
TI  - Scaling behavior of amorphous FeMn in magnetic fields.

PMID- 9937680
TI  - Two-dimensional molecular diffusion and phase transitions in HNO3-intercalated
      graphite studied by quasielastic neutron scattering.

PMID- 9937679
TI  - Scaling and iterative-map treatment of quantum percolation on a diluted linear
      chain and nonrandom fractals.

PMID- 9937681
TI  - Density and size of neon bubbles in molybdenum, tantalum, and tantalum oxide.

PMID- 9937682
TI  - Metastability in the random-field Ising model.

PMID- 9937684
TI  - Calculated electronic profiles for liquid-metal surfaces.

PMID- 9937683
TI  - Pressure-induced first-order transition associated with 4f instability in CeNi.

PMID- 9937685
TI  - Vacancy migration and accretion in Ni observed by perturbed gamma - gamma angular
      correlations.

PMID- 9937687
TI  - Ab initio calculations of selected ionization states of Cu on MgO(001).

PMID- 9937686
TI  - Various approximations made in augmented-plane-wave calculations.

PMID- 9937688
TI  - Unified description of "constant-volume" and "bond-breaking" pair potentials in
      metals.

PMID- 9937689
TI  - Structural characterization of metal-metal interfaces by intermediate-energy
      Auger-electron diffraction.

PMID- 9937690
TI  - Linear augmented-Slater-type-orbital method for electronic-structure
      calculations. II. bcc, fcc, and hcp W.

PMID- 9937691
TI  - Linear augmented-Slater-type-orbital method for electronic-structure
      calculations. III. Structural and cohesive energies of the 5d elements Lu-Au.

PMID- 9937692
TI  - Indexing problems in quasicrystal diffraction.

PMID- 9937693
TI  - 2p absorption spectra of the 3d elements.

PMID- 9937694
TI  - L2,3 absorption spectra of the lighter 3d transition metals.

PMID- 9937695
TI  - Effect of exciton hopping upon the mass of an exciton.

PMID- 9937696
TI  - Surface-polariton-induced structure in the I-V curves of metal-insulator-metal
      tunnel junctions.

PMID- 9937697
TI  - Energy of planar arrays of point charges with two- and three-dimensional
      backgrounds.

PMID- 9937698
TI  - Lattice dynamics of rare-gas overlayers on smooth surfaces.

PMID- 9937700
TI  - Spin-orbit effects on the bulk penetration and energy shift of Tamm states on
      Cu(001) and Ag(001).

PMID- 9937699
TI  - Investigation of the appropriateness of sensitized luminescence to determine
      exciton motion parameters in pure molecular crystals.

PMID- 9937701
TI  - Thermodynamic properties of bcc crystals at high temperatures: The transition
      metals.

PMID- 9937702
TI  - Fermi velocities in silver: Surface Landau-level resonances.

PMID- 9937703
TI  - Electron-phonon scattering in silver: Surface Landau-level resonance.

PMID- 9937704
TI  - Electromagnetic response of systems with spatial fluctuations. I. General
      formalism.

PMID- 9937705
TI  - Electromagnetic response of systems with spatial fluctuations. II. Applications.

PMID- 9937706
TI  - Alternative self-energy expression for the Anderson model.

PMID- 9937707
TI  - Thermodynamic variational method for liquid alloys with chemical short-range
      order.

PMID- 9937708
TI  - Self-consistent electronic structure of lithium clusters.

PMID- 9937710
TI  - Experimental band structure of ordered Cu overlayers on Ag(001).

PMID- 9937709
TI  - Adsorption probabilities of H2 and D2 on various flat and stepped nickel
      surfaces.

PMID- 9937711
TI  - Sensitivity of helium diffraction to surface geometry.

PMID- 9937712
TI  - Calculation of elastic strain and electronic effects on surface segregation.

PMID- 9937713
TI  - Grating-induced cross coupling of surface polaritons.

PMID- 9937714
TI  - Work-function changes due to surface anisotropy and imperfections.

PMID- 9937715
TI  - Grazing-incidence antireflection films. I. Basic theory.

PMID- 9937716
TI  - Grazing-incidence antireflection films. II. Alternate techniques and general
      multilayer theory.

PMID- 9937717
TI  - p-polarized nonlinear surface polaritons in materials with intensity-dependent
      dielectric functions.

PMID- 9937718
TI  - Structural relaxation of Co-P amorphous alloys.

PMID- 9937719
TI  - 3d x-ray-absorption lines and the 3d94fn+1 multiplets of the lanthanides.

PMID- 9937720
TI  - X-ray spectra of model binary alloys A1-xBx.

PMID- 9937721
TI  - Core-level binding-energy shifts due to end effects in polymers: A Hartree-Fock
      Green's-function study.

PMID- 9937722
TI  - Optical determination of the antiferromagnetic exchange constant between nearest
      neighbor Mn2+ ions in Cd0.95Mn0.05Te.

PMID- 9937723
TI  - Calculations of hole subbands in semiconductor quantum wells and superlattices.

PMID- 9937724
TI  - Magnetization and magnetoreflectance in Zn1-xMnxTe.

PMID- 9937725
TI  - Cluster formation and atomic intermixing at the reactive V/Ge(111) interface.

PMID- 9937726
TI  - Far-infrared powder absorption measurements of some
      tetramethyltetraselenafulvalene salts

PMID- 9937727
TI  - Phonon-induced Raman processes connecting the E-bar( 2E) and 2A-bar( 2E) states
      in ruby.

PMID- 9937728
TI  - Inelastic light scattering by collective charge-density excitations in semi
      infinite semiconductor superlattices.

PMID- 9937729
TI  - General theory of the transverse dielectric constant of III-V semiconducting
      compounds.

PMID- 9937730
TI  - Self-consistent phonon theory of mean-field hydrogen-bond melting of poly(dG)
      poly(dC).

PMID- 9937731
TI  - Acceptor spectra of AlxGa1-xAs-GaAs quantum wells in external fields: Electric,
      magnetic, and uniaxial stress.

PMID- 9937732
TI  - Optical absorption studies in Cd1-xMnxSe.

PMID- 9937733
TI  - Two-dimensional electron-hole fluid in a strong perpendicular magnetic field:
      Exciton Bose condensate or maximum density two-dimensional droplet.

PMID- 9937734
TI  - Spatially varying band structures.

PMID- 9937735
TI  - Cyclotron resonance in the two-dimensional hole gas in (Ga,Al)As/GaAs
      heterostructures.

PMID- 9937736
TI  - Conduction-band dispersion, critical points, and unoccupied surface states on
      GaAs(110): A high-resolution angle-resolved inverse photoemission study.

PMID- 9937737
TI  - Focusing of large-wave-vector phonons in GaAs.

PMID- 9937738
TI  - Atomic model for the M center in InP.

PMID- 9937739
TI  - Asymmetry of anion and cation vacancy migration enthalpies in III-V compound
      semiconductors: Role of the kinetic energy.

PMID- 9937740
TI  - Electronic Raman spectra of shallow acceptors in semi-insulating GaAs.

PMID- 9937742
TI  - Electron subbands and transport properties in inversion layers of InAs and InP.

PMID- 9937741
TI  - Self-consistent-field cluster calculations of Ni2+ centers in cubic ZnS, CdS, and
      ZnSe in the complete-neglect-of-differential-overlap approximation.

PMID- 9937743
TI  - Properties of electron-hole liquid in highly stressed silicon.

PMID- 9937744
TI  - Effect of electron correlation on the ground state, the singlet-exciton states,
      and the triplet-exciton states of trans-polyacetylene.

PMID- 9937745
TI  - Raman resonance on E1 edges in superlattices.

PMID- 9937747
TI  - Determination of the shear deformation-potential constant in electron space
      charge layers on Si surfaces by tunneling.

PMID- 9937746
TI  - Densities of phonon states for (GaSb)1-x(Ge2)x.

PMID- 9937748
TI  - Energy localization in rapidly deforming crystalline solids.

PMID- 9937749
TI  - Average phonon decay rate in anharmonic insulators.

PMID- 9937750
TI  - Structure and selectively enhanced Raman spectra of high-silica alkali-silicate
      glasses.

PMID- 9937751
TI  - T3 specific-heat anomaly in network solids.

PMID- 9937752
TI  - Stability and instability in crystal growth: Symmetric solutions of the Stefan
      problem.

PMID- 9937754
TI  - Growth of Ce-Nb oxide films: A test of oxidation theory.

PMID- 9937753
TI  - Static spin correlations in alternant quantum cell models.

PMID- 9937755
TI  - Interaction of SO2 and CO with the Ti2O3(101-bar2) surface.

PMID- 9937756
TI  - Molecular-cluster study of core-level x-ray photoelectron spectra: Application to
      FeCl2.

PMID- 9937757
TI  - Interactions, local order, and atomic-rearrangement kinetics in amorphous nickel
      phosphorous alloys.

PMID- 9937758
TI  - Vacancy distribution and ionic motion in LaF3 studied by 19F NMR.

PMID- 9937759
TI  - Effect of the internal field on polarization and depolarization experiments on
      SrF2:La3+

PMID- 9937760
TI  - Tracks of heavy ions in muscovite mica: Analysis of the rate of production of
      radiation defects.

PMID- 9937761
TI  - Charge-transfer effects in oxygen chemisorption on nickel (001).

PMID- 9937763
TI  - Diffraction of evanescent x-rays: Results from a dynamical theory.

PMID- 9937762
TI  - Short-range order of fluctuating moments in iron.

PMID- 9937764
TI  - Thermal conductance and giant fluctuations in one-dimensional disordered systems.

PMID- 9937765
TI  - Band offsets from two special GaAs-AlxGa1-xAs quantum-well structures.

PMID- 9937766
TI  - Exact linear admittance of n+-n-n+ semiconductor structures.

PMID- 9937768
TI  - Electro-optic contribution to field-induced Raman scattering in alkali halides.

PMID- 9937767
TI  - Viscous-liquid-like electron state in the dilute-metal-like n-type Hg0.8Cd0.2Te.

PMID- 9937769
TI  - Surface plasmon of a semiconductor superlattice.

PMID- 9937771
TI  - Correlation between the self-diffusion coefficient of lithium and the equation of
      state.

PMID- 9937770
TI  - Solid-state effects in photoionization cross sections of d states: Comparison
      between MoS2 and Mo.

PMID- 9937772
TI  - Raman scattering in ultraheavily doped silicon.

PMID- 9937773
TI  - Effect of lattice connectivity on the electronic structure of an amorphous
      semiconductor.

PMID- 9937774
TI  - Unified study of lattice dynamics of alkali metals with the use of a general
      tensor force model.

PMID- 9937775
TI  - Comments on the kinetics of hydrogen uptake on niobium surfaces.

PMID- 9937776
TI  - Reply to "Comments on the kinetics of hydrogen uptake on niobium surfaces"

PMID- 9937777
TI  - Comment on Kimball's formula relating the pair correlation function at the origin
      to the structure factor at short wavelengths.

PMID- 9937778
TI  - Low-temperature ultrasonic study of trapped hydrogen in niobium.

PMID- 9937779
TI  - Erratum: Calculations of transfer integrals for tetracyanoquinodimethane salts

PMID- 9937781
TI  - Quantization of the magnetic induction for two-dimensional electronic systems.

PMID- 9937780
TI  - Absence of energy loss in positron emission from metal surfaces.

PMID- 9937782
TI  - Zr1-xMoxN as a high-Tc superconductor.

PMID- 9937784
TI  - Splitting of the surface-plasmon dispersion on a slightly rough surface studied
      by attenuated total reflection.

PMID- 9937783
TI  - Electron-emission processes following 5p photoexcitation in fcc Yb.

PMID- 9937785
TI  - Core-level spectra of Th compounds.

PMID- 9937787
TI  - Distribution of the quantized Hall potential in GaAs-AlxGa1-xAs heterostructures.

PMID- 9937786
TI  - X-ray standing-wave fluorescence analysis of electrodeposited Tl on clean and
      oxygen-reconstructed Cu(111).

PMID- 9937788
TI  - Intrinsic dangling-bond density in hydrogenated amorphous silicon.

PMID- 9937789
TI  - Far-infrared absorption spectra of the ground-state-to- excited-state transitions
      of excitons bound to the double acceptors Be and Zn in Ge.

PMID- 9937790
TI  - Effect of band hybridization on exciton states in GaAs-AlxGa1-xAs quantum wells.

PMID- 9937791
TI  - Band-mixing effect on the emission spectrum of modulation-doped semiconductor
      quantum wells.

PMID- 9937792
TI  - Core-excitonic lines at the Al 2p surface optical-absorption threshold of AlAs
      and AlP.

PMID- 9937793
TI  - Quantum size effects in simple colored glass.

PMID- 9937794
TI  - Bunching of streaming carriers in p-type Ge at intense microwave fields.

PMID- 9937795
TI  - Complete charge density-wave mode locking and freeze-out of fluctuations in
      NbSe3.

PMID- 9937796
TI  - Size effects on electron-electron interactions in GaAs-AlxGa1-xAs
      heterostructures.

PMID- 9937797
TI  - Cyclotron resonance of localized electrons in n-type Cd-Mn-Se.

PMID- 9937798
TI  - Quasicrystals with arbitrary orientational symmetry.

PMID- 9937799
TI  - ir overtone spectrum of the vibrational soliton in crystalline acetanilide.

PMID- 9937800
TI  - Diffusion and intercalation of fluorine into highly oriented pyrolytic graphite:
      An in situ ESR study.

PMID- 9937802
TI  - Interface states and subbands in HgTe-CdTe heterostructures.

PMID- 9937803
TI  - Experimental investigation of the general slow-tumbling ESR theory for completely
      anisotropic hyperfine centers in amorphous condensed matter.

PMID- 9937801
TI  - Raman scattering study of amorphous Si-Ge interfaces.

PMID- 9937805
TI  - Investigation of EPR in Cd1-xMnxTe by microwave Faraday effect.

PMID- 9937804
TI  - Hyperfine interactions and magnetic properties of amorphous Fe-Sb alloys.

PMID- 9937806
TI  - Magnetic order in the diluted antiferromagnet K2FexZn1-xF4 studied with Mossbauer
      spectroscopy and neutron diffraction.

PMID- 9937807
TI  - Spin diffusion in resolved solid-state NMR spectra.

PMID- 9937808
TI  - Locator study of neutron and light inelastic scattering and infrared absorption
      in disordered solids.

PMID- 9937809
TI  - Dissipation in combined normal and superfluid flows of He II: A unified
      description.

PMID- 9937810
TI  - Double-valence-fluctuating molecules and superconductivity.

PMID- 9937812
TI  - Localized superconductors.

PMID- 9937811
TI  - Parallel-plate waveguides for studies of fifth sound and third sound without
      vapor exchange.

PMID- 9937813
TI  - Compression experiments with spin-polarized atomic hydrogen.

PMID- 9937814
TI  - de Haas-van Alphen scattering measurements on the reentrant superconductor La1
      xCexAl2.

PMID- 9937815
TI  - Theory of inhomogeneous quantum systems. IV. Variational calculations of metal
      surfaces.

PMID- 9937817
TI  - Glasslike properties of a chain of particles with anharmonic and competing
      interactions.

PMID- 9937816
TI  - Liquid helium on a surface: Ground state, excitations, condensate fraction, and
      impurity potential.

PMID- 9937818
TI  - Boundary conditions in dynamical neutron diffraction.

PMID- 9937820
TI  - Symmetry, stability, and elastic properties of icosahedral incommensurate
      crystals.

PMID- 9937819
TI  - Dynamical neutron diffraction in a thick-crystal interferometer.

PMID- 9937822
TI  - Monte Carlo study of the local-field distribution in the dilute antiferromagnetic
      Ising model on the triangular lattice.

PMID- 9937821
TI  - Critical behavior of pure and diluted XY models with uniform frustrations.

PMID- 9937823
TI  - Low-temperature thermal properties of ferroelectrics.

PMID- 9937824
TI  - NMR study of local magnetizations in diluted two-dimensional antiferromagnets.

PMID- 9937825
TI  - Crossover in spectral dimensionality of elastic percolation systems.

PMID- 9937826
TI  - Soliton specific heat of spin chains: Limitations of the quantum sine-Gordon
      model.

PMID- 9937827
TI  - Unusual long-range-order property of the Ising model on the Sierpin-acuteski
      gasket.

PMID- 9937828
TI  - Renormalization-group theory of spinodal decomposition.

PMID- 9937829
TI  - Molecular symmetry and translation-rotation coupling in orientationally
      disordered crystals.

PMID- 9937831
TI  - Paramagnetic resonance and local position of Cr3+ in ferroelectric BaTiO3.

PMID- 9937830
TI  - Local properties in orientationally disordered crystals with translation-rotation
      coupling.

PMID- 9937832
TI  - Implications of direct-product ground states in the one-dimensional quantum XYZ
      and XY spin chains.

PMID- 9937834
TI  - Model for incipient triple point in krypton and nitrogen adsorbed on graphite.

PMID- 9937833
TI  - Redundant operators for Ising spins.

PMID- 9937835
TI  - Kinetic behavior of the Baxter-Wu model with quenched impurities.

PMID- 9937839
TI  - Interface and guided magnetic polariton modes in magnetic structure.

PMID- 9937842
TI  - Thermal conductivity of 4He I from near T lambda to 3.6 K and vapor pressure to
      30 bars.

PMID- 9937836
TI  - Magnetic octupole neutron scattering and quadrupolar excitations above and below
      the magnetic ordering temperature: Analysis using octupolar correlation
      functions.

PMID- 9937838
TI  - Nucleation in emulsified supercooled water.

PMID- 9937837
TI  - Phase transformations and ordering in polyacetylene.

PMID- 9937841
TI  - Theory of surface effects in binary alloys with fcc crystal structure: A Landau
      approach.

PMID- 9937843
TI  - Finite-size corrections in the XYZ Heisenberg chain.

PMID- 9937845
TI  - Renormalization-group results of electronic states in a one-dimensional system
      with incommensurate potentials.

PMID- 9937844
TI  - Spin susceptibility in three-dimensional nearly magnetic disordered fermion
      systems in the weakly localized regime.

PMID- 9937840
TI  - Wilson's renormalization-group approach to a d-dimensional quantum sine-Gordon
      model.

PMID- 9937848
TI  - Theory of the low-temperature phases in boracites: Latent antiferromagnetism,
      weak ferromagnetism, and improper magnetostructural couplings.

PMID- 9937851
TI  - Electrostatic edge modes of a hyperbolic dielectric wedge: Analytical solution.

PMID- 9937846
TI  - Multilayer wetting phenomenon at a binary liquid-vapor interface. I. Theory.

PMID- 9937847
TI  - Multilayer wetting phenomenon at a binary liquid-vapor interface. II. Comparison
      with experiment.

PMID- 9937849
TI  - Superconducting-fluctuation conductivity of one-dimensional wires in a magnetic
      field.

PMID- 9937850
TI  - Neutron-diffraction studies of UBe13and ThBe13.

PMID- 9937852
TI  - Superconducting Tc enhancement in weakly disordered Ge-covered tin films.

PMID- 9937854
TI  - Determination of percolation probability from the use of a concentration
      gradient.

PMID- 9937855
TI  - Z(4) model: Criticality and break-collapse method.

PMID- 9937853
TI  - Isothermal molecular-dynamics calculations.

PMID- 9937856
TI  - Numerical simulations and exactly soluble spin-glass models.

PMID- 9937857
TI  - Erratum: Theory of ferromagnetic resonance and static magnetization in ultrathin
      crystals

PMID- 9937859
TI  - Determination of the random-walk dimension of fractals by means of NMR.

PMID- 9937863
TI  - Structure of axially compressed monolayers of N2 physisorbed on graphite.

PMID- 9937860
TI  - Experimental support for physisorbed positronium at the surface of quartz.

PMID- 9937861
TI  - Spin fluctuations and superconductivity in UPt3.

PMID- 9937862
TI  - Strain distortion in anisotropic superconductors.

PMID- 9937864
TI  - Anisotropic magnetoresistance of amorphous and concentrated polycrystalline iron
      alloys.

PMID- 9937858
TI  - Two-level systems in hydrogenated amorphous silicon: NMR studies.

PMID- 9937865
TI  - Clear evidence of redundant operators in Monte Carlo studies of the Ising model.

PMID- 9937870
TI  - Scaling theory of the low-field Hall effect near the percolation threshold.

PMID- 9937871
TI  - Specific heat of a Coqblin-Schrieffer model with crystal fields: New crossover
      features and scaling properties.

PMID- 9937869
TI  - Spin-lattice relaxation in fractal systems.

PMID- 9937866
TI  - Sum-rule violations near tricriticality.

PMID- 9937867
TI  - Conformal mapping of a periodic strip at criticality.

PMID- 9937875
TI  - Magnetic structure and dynamics in the alpha and beta phases of solid oxygen.

PMID- 9937868
TI  - Explanation for the universal low-temperature and dynamical properties of a
      particular glass.

PMID- 9937873
TI  - Equivalence of real-space renormalization groups for quantum systems and for
      critical dynamics.

PMID- 9937872
TI  - Hyperfine-magnetic-field measurements in the Heusler alloy Ni2MnGa.

PMID- 9937874
TI  - Interface models and the bulk phase transition of Ising systems.

PMID- 9937876
TI  - NMR in high-pressure phases of solid NH3 and ND3.

PMID- 9937877
TI  - Near-edge structure in electron-energy-loss spectra of MgO.

PMID- 9937879
TI  - Spin diffusion in block copolymers as studied by pulsed NMR.

PMID- 9937882
TI  - Model-independent NMR approach in determining hydrogen diffusion in titanium
      hydride.

PMID- 9937878
TI  - One-dimensional quantum rotator in solids: The para-ortho transition of H2S- in
      KCl.

PMID- 9937881
TI  - Bloch waves and band structure for diffracted and channeled particles in
      crystals.

PMID- 9937880
TI  - Self-consistent wake binding energies.

PMID- 9937883
TI  - NMR study of hydrogen diffusion in zirconium hydride.

PMID- 9937887
TI  - Resonant Raman scattering in a bis-tetramethyltetraselenafulvalene
      hexafluorophosphate

PMID- 9937885
TI  - One-body density matrix for quantum fluids in the diagonal limit.

PMID- 9937884
TI  - Twisting in superfluid 3He-A and consequences for hydrodynamics at T=0.

PMID- 9937886
TI  - Irrelevance of bulk symmetry to critical wetting.

PMID- 9937890
TI  - Influence of impurities and magnetic fields on the normal and superconducting
      states of UBe13.

PMID- 9937889
TI  - Light scattering in the high-temperature superconductor Ba(Pb1-xBix)O3.

PMID- 9937888
TI  - Flow and torsional oscillator measurements on liquid helium in restricted
      geometries under pressure.

PMID- 9937892
TI  - Porous-membrane second-sound transducers for superfluid 4He.

PMID- 9937893
TI  - Theoretical studies of the dynamic structure function of liquid 4He.

PMID- 9937891
TI  - Acoustic-property measurements of the oxide superconductor BaPb1-xBixO3 by the
      sphere-resonance method.

PMID- 9937903
TI  - Structure of a solid film on an imperfect surface.

PMID- 9937898
TI  - Transverse attenuation coefficients for superconductors containing transition
      metal impurities.

PMID- 9937894
TI  - Superconducting and magnetic properties of (Th1-xNdx)Ru2 and (Th1-xLax)Ru2
      intermetallic compounds.

PMID- 9937899
TI  - Neutral-ionic transition and dimerization in organic mixed-stack compounds.

PMID- 9937900
TI  - Experimental evidence for a Mott-Wigner glass phase of magnetite above the Verwey
      temperature.

PMID- 9937895
TI  - Perturbation treatment of boundary conditions for fluxon motion in long Josephson
      junctions.

PMID- 9937897
TI  - Thermal conductivity of 4He I near T lambda from vapor pressure to 28 bars:
      Comparison of experiment and theory.

PMID- 9937896
TI  - Switching between dynamic states in intermediate-length Josephson junctions.

PMID- 9937902
TI  - Renormalization-group analysis of heat-capacity critical amplitudes.

PMID- 9937901
TI  - Variational theory of valence fluctuations: Ground states and quasiparticle
      excitations of the Anderson lattice model.

PMID- 9937905
TI  - Localized fluidity modes and the topology of the constant-potential-energy
      hypersurfaces of Lennard-Jones matter.

PMID- 9937904
TI  - Ordering in ferromagnets with random anisotropy.

PMID- 9937906
TI  - Power-law correlations and finite-size effects in silica particle aggregates
      studied by small-angle neutron scattering.

PMID- 9937910
TI  - Microscopic approach to macroscopic dynamics in XY spin glasses.

PMID- 9937909
TI  - Variational approach to finite-temperature magnetism. II. Antiferromagnetism.

PMID- 9937908
TI  - Anisotropy in binary metallic spin-glass alloys. II. Rare earths.

PMID- 9937907
TI  - Anisotropy in binary metallic spin-glass alloys. I. Transition metals.

PMID- 9937911
TI  - Phenomenological dynamics of XY spin glasses.

PMID- 9937914
TI  - Periodic Kondo-Hubbard model for a quasi-one-dimensional organic ferromagnet m
      polydiphenylcarbene: Cooperation between electron correlation and topological
      structure.

PMID- 9937912
TI  - Phonon calculations of thermodynamic properties of solid 4He above its high
      pressure triple point.

PMID- 9937913
TI  - Magnetic ground state of metallic hydrogen and lithium in the low-density limit.

PMID- 9937915
TI  - Constant-temperature-constant-pressure molecular-dynamics calculations for
      molecular solids: Application to solid nitrogen at high pressure.

PMID- 9937917
TI  - S=1/2 antiferromagnetic finite chains effectively isolated by frustration: CuCl2
      intercalated graphite.

PMID- 9937916
TI  - Spin-glass transition of a dilute Ag-Mn alloy in a magnetic field.

PMID- 9937920
TI  - Early-time instabilities in a dynamic percolation model.

PMID- 9937918
TI  - Nearest-neighbor exchange constant and Mn distribution in Zn1-xMnxTe from high
      field magnetization step and low-field susceptibility.

PMID- 9937923
TI  - Resistance fluctuations in random resistor networks above and below the
      percolation threshold.

PMID- 9937919
TI  - Exchange interactions in the quasi-one-dimensional mixed antiferromagnet CsCo1
      xFexCl3: A light-scattering study.

PMID- 9937921
TI  - Systematic deviation from scaling in the dynamics of a random interface: Case for
      a nonzero initial order parameter.

PMID- 9937922
TI  - Dynamics of the one-dimensional Potts model.

PMID- 9937924
TI  - Wetting of a glass substrate by a binary liquid mixture.

PMID- 9937925
TI  - Growth mode and phase transitions of multilayer nitrogen on graphite.

PMID- 9937926
TI  - Local symmetries and structural distortions in amorphous ferromagnetic metals: A
      study of their contributions to the aftereffect of the magnetic permeability.

PMID- 9937927
TI  - Local magnetic fields in ferromagnetic intermetallic compounds of cubic Laves
      phase type.

PMID- 9937928
TI  - Critical behavior of the six-state clock model in two dimensions.

PMID- 9937929
TI  - Nuclear magnetism in a metal.

PMID- 9937930
TI  - Symmetry analysis and Monte Carlo study of a frustrated antiferromagnetic planar
      (XY) model in two dimensions.

PMID- 9937931
TI  - Random binary alloy. I. Formulation of the method of the distribution function.

PMID- 9937932
TI  - Random binary alloy. II. Gaussian distributions and the limit of infinite-range
      interactions.

PMID- 9937934
TI  - Conductivity of a square-lattice bond-mixed resistor network.

PMID- 9937933
TI  - Low-density phase diagram of the two-dimensional Coulomb gas.

PMID- 9937935
TI  - Large anisotropic thermal expansion and magnetostriction in the mixed-valence
      compound CeNi.

PMID- 9937936
TI  - High-temperature critical behavior of square-lattice planar models: A series
      investigation.

PMID- 9937937
TI  - Amorphization of the Ising ferromagnet with a transverse field.

PMID- 9937939
TI  - Dynamic diffusion in the d-dimensional termite model.

PMID- 9937940
TI  - Multichannel Landauer formula for thermoelectric transport with application to
      thermopower near the mobility edge.

PMID- 9937941
TI  - Quantum spin glass: A replica-symmetric theory with positive entropy.

PMID- 9937938
TI  - Many-body effects in the paramagnetic and antiferromagnetic states of the (111)
      silicon face.

PMID- 9937945
TI  - Ligand hyperfine spectra of Cu2+ in AgCl.

PMID- 9937942
TI  - Magnetic phase diagram of EuxLa1-xS.

PMID- 9937944
TI  - Mossbauer study of monoclinic FeCr2SexS4-x.

PMID- 9937943
TI  - Low-temperature specific heat of uranium monosulfide.

PMID- 9937946
TI  - M2,3NN Auger emission of K excited with low-energy Ar+ and K+ projectiles.

PMID- 9937947
TI  - Thermodynamic and far-infrared properties of V3Si calculated from tunneling
      results for the Eliashberg function alpha 2F and Coulomb pseudopotential
      parameter micro.

PMID- 9937948
TI  - Oscillating and rotating sine-Gordon system.

PMID- 9937949
TI  - Vortex dynamics of superfluid helium films on spherical surfaces.

PMID- 9937953
TI  - Fractal lattices and universality.

PMID- 9937954
TI  - Complete-wetting exponents from capillary-wave theory.

PMID- 9937951
TI  - Full splitting of the first zero-field steps in the I-V curve of Josephson
      junctions of intermediate length.

PMID- 9937950
TI  - Model for p- and d-wave superconductivity in heavy-fermion systems.

PMID- 9937952
TI  - Magnetic exchange constant in Zn1-xMnxTe.

PMID- 9937955
TI  - First-order valence phase transition in cubic YbxIn1-xCu2.

PMID- 9937957
TI  - Comment on "Critical relaxation of the one-dimensional Blume-Emery-Griffiths
      model"

PMID- 9937959
TI  - Interaction of spin waves with magnetic two-level systems in amorphous magnets.

PMID- 9937956
TI  - Comment on "Resonant coupling between one- and two-magnon excitations in
      tetramethylamine manganese trichloride (TMMC)"

PMID- 9937961
TI  - Spin exchange and dipolar relaxation rates in atomic hydrogen: Lifetimes in
      magnetic traps.

PMID- 9937958
TI  - Reply to "Comment on 'Critical relaxation of the one-dimensional Blume-Emery
      Griffiths model' "

PMID- 9937960
TI  - Erratum: Dynamic scaling in the Eu0.4Sr0.6S spin-glass

PMID- 9937962
TI  - Anomalous nuclear magnetic susceptibility of platinum powder.

PMID- 9937965
TI  - Long-range k-d correlation among droplets in quenched systems in d dimensions.

PMID- 9937964
TI  - Structure of liquid 4He at low temperatures: Random-phase approximation.

PMID- 9937966
TI  - Localization of electrons with spin-orbit or magnetic interactions in a two
      dimensional disordered crystal.

PMID- 9937968
TI  - Nyquist noise in a fractal resistor network.

PMID- 9937969
TI  - Site-bond correlated model for disordered magnets: Mean-field theory.

PMID- 9937963
TI  - Multiple sites and mobility in ionic conductors by NMR dipolar transient effects.

PMID- 9937967
TI  - Time decay of the remanent magnetization in a CuMn spin glass.

PMID- 9937971
TI  - Gap of the linear spin-1 Heisenberg antiferromagnet: A Monte Carlo calculation.

PMID- 9937970
TI  - Commensurate-incommensurate transition of Kr-Xe mixtures on graphite.

PMID- 9937972
TI  - Observation of an order-disorder phase transition on the Pd(110) surface.

PMID- 9937975
TI  - Spin-spin correlations in finite systems: Scaling hypothesis and corrections to
      bulk behavior.

PMID- 9937974
TI  - Structural relaxation in the Al86Mn14 quasicrystal.

PMID- 9937976
TI  - Electric field gradient at the nucleus of alkali-metal atoms adsorbed on jellium.

PMID- 9937973
TI  - Long-range interactions between local moments in metals: Application to spin
      glass systems.

PMID- 9937977
TI  - Schottky-barrier height of a Ti-W alloy on n-type and p-type Si.

PMID- 9937978
TI  - Nonlocal density functional for the exchange and correlation energy of electrons.

PMID- 9937979
TI  - Experimental study of surface states on the (110) faces of the noble metals.

PMID- 9937980
TI  - Light scattering spectrum of one-dimensional mixed crystals.

PMID- 9937981
TI  - Oscillatory behavior of the agglomeration rate in island copper films.

PMID- 9937982
TI  - Theoretical Compton profiles of graphite and LiC6.

PMID- 9937983
TI  - Dielectric properties of silver-gelatin granular suspensions.

PMID- 9937984
TI  - Important electron-electron interaction and spin-orbit effects in thin copper
      films.

PMID- 9937985
TI  - Half-flux quantum magnetoresistance oscillations in the ladder configuration.

PMID- 9937986
TI  - Photoemission and Auger-electron spectroscopic study of the Chevrel-phase
      compound FexMo6S8.

PMID- 9937988
TI  - Effective Hamiltonians for phonon-coupled and spatially confined systems.

PMID- 9937987
TI  - Diffusion of hydrogen in alpha '-VHx.

PMID- 9937989
TI  - Stability of 4f configurations in rare-earth-metal compounds.

PMID- 9937991
TI  - Sliding charge-density waves: A numerical study.

PMID- 9937990
TI  - Theoretical and experimental study of the unoccupied electronic band structure of
      Ru(001) by electron reflection.

PMID- 9937992
TI  - Electronic structure of substoichiometric carbides and nitrides of zirconium and
      niobium.

PMID- 9937994
TI  - Fermi surface of field-induced ferromagnetic CeSb.

PMID- 9937993
TI  - Soliton lattice structure and midgap band in nearly commensurate charge-density
      wave states.

PMID- 9937996
TI  - Dynamic structure of electrons in Li metal: Inelastic synchrotron x-ray
      scattering results and interpretation beyond the random-phase approximation.

PMID- 9937995
TI  - Indirect-exchange interaction near a metal surface.

PMID- 9937998
TI  - Phonon anomalies and linewidths in Nb at 10 K.

PMID- 9937997
TI  - Surface vibrations and (2 x 1) superstructures on fcc (110) metal surfaces.

PMID- 9937999
TI  - Enhanced second-harmonic generation by surface polaritons on thin metal films.

PMID- 9938001
TI  - Nonlinear pressure dependence of the bulk modulus of TmSe.

PMID- 9938000
TI  - Atomic structure of the Si(001)c(4 x 2) surface.

PMID- 9938002
TI  - Equation of state and metallization of neon.

PMID- 9938003
TI  - Temperature measurement of sputtered metal dimers.

PMID- 9938004
TI  - Angle-resolved photoemission determination of the band structure of Ru(001).

PMID- 9938005
TI  - Magnetoresistance of the organic conducting tetramethyltetraselenafulvalene salts
      (TMTSF)2ClO4 and (TMTSF)2PF6: Search for the coherent-diffusive transition or
      localization effects with increasing temperature.

PMID- 9938006
TI  - Emission dynamics from doped crystals of (CH3)4NMnCl3 (TMMC): Exciton trapping in
      a one-dimensional lattice.

PMID- 9938007
TI  - Electroreflectance spectroscopy of Si-GexSi1-x quantum-well structures.

PMID- 9938008
TI  - Effects of charge-density-wave depinning on the elastic properties of
      orthorhombic TaS3.

PMID- 9938009
TI  - Chemisorption of H2O on GexSil-x(100)(2 x 1).

PMID- 9938010
TI  - Shallow donors in magnetic fields in zinc-blende semiconductors. I. Theory.

PMID- 9938012
TI  - Quantum Hall effect in silicon metal-oxide-semiconductor inversion layers:
      Experimental conditions for determination of h/e2.

PMID- 9938011
TI  - Shallow donors in magnetic fields in zinc-blende semiconductors. II. Magneto
      optical study of InSb under hydrostatic pressure.

PMID- 9938013
TI  - Effects of interface charge on the quantum Hall effect.

PMID- 9938014
TI  - Interacting donors in n-type GaP studied with Raman scattering and ESR
      techniques.

PMID- 9938015
TI  - Inversion electrons on narrow-band-gap semiconductors in crossed electric and
      magnetic fields.

PMID- 9938016
TI  - Dielectric interpretation of Lei-Ting nonlinear force-momentum-balance transport
      equation for isothermal resistivity.

PMID- 9938018
TI  - Change in sound velocity due to sliding charge-density waves.

PMID- 9938017
TI  - Schottky barriers on phosphorus-doped hydrogenated amorphous silicon: The effects
      of tunneling.

PMID- 9938019
TI  - Far-infrared nonlinear optics. I. chi (2) near ionic resonance.

PMID- 9938020
TI  - Far-infrared nonlinear optics. II. chi (3) contributions from the dynamics of
      free carriers in semiconductors.

PMID- 9938021
TI  - Disorder representations and self-consistent effective-medium theories for
      spatially extended quasiparticles in alloys.

PMID- 9938022
TI  - Relation between electroabsorption in bulk semiconductors and in quantum wells:
      The quantum-confined Franz-Keldysh effect.

PMID- 9938023
TI  - Photoemission study of Si(111)-Ge(5 x 5) surfaces.

PMID- 9938024
TI  - Effect of compressive uniaxial stress on the binding energies of D- centers in
      Si:P and Si:As.

PMID- 9938025
TI  - Electronic properties of the precrystallization regime of germanium: A
      photoemission study.

PMID- 9938026
TI  - Phonon coupling in optical transitions for singlet-triplet pairs of bound
      excitons in semiconductors.

PMID- 9938028
TI  - Ab initio calculation of the macroscopic dielectric constant in silicon.

PMID- 9938027
TI  - X-ray diffraction evidence of adatoms in the Si(111)7 x 7 reconstructed surface.

PMID- 9938029
TI  - Correlation between physical properties and hydrogen concentration in magnetron
      sputtered amorphous silicon.

PMID- 9938030
TI  - Interdiffusion and reaction at the Fe/GaAs(110) interface.

PMID- 9938031
TI  - Structures and magic numbers of group-IV microclusters calculated by use of an
      anisotropic model potential.

PMID- 9938032
TI  - Luminescence of n-i-p-i heterostructures.

PMID- 9938034
TI  - Quantum theory of transient transport in an interacting system of electrons,
      impurities, and phonons.

PMID- 9938033
TI  - Theory of impurity-doping effect on electronic states in a quasi-one-dimensional
      structure semiconductor.

PMID- 9938035
TI  - Local atomic structure in thin films of silicon nitride and silicon diimide
      produced by remote plasma-enhanced chemical-vapor deposition.

PMID- 9938036
TI  - Schottky-barrier heights of single-crystal NiSi2 on Si(111): The effect of a
      surface p-n junction.

PMID- 9938037
TI  - Theory of the lateral surface magnetoplasmon in a semiconductor superlattice.

PMID- 9938039
TI  - Theoretical investigation of the electrical and optical activity of vanadium in
      GaAs.

PMID- 9938038
TI  - New technique for molecular-dynamics computer simulations: Hellmann-Feynman
      theorem and subspace Hamiltonian approach.

PMID- 9938040
TI  - Solid versus fluid, and the interplay between fluctuations, correlations, and
      exchange in the fractional quantized Hall effect.

PMID- 9938041
TI  - Thermoelectric properties of GaAs-Ga1-xAlxAs heterojunctions at high magnetic
      fields.

PMID- 9938042
TI  - Indirect-exchange interaction between localized moments in semiconductors.

PMID- 9938043
TI  - Pseudopotential inversion scheme.

PMID- 9938044
TI  - Systematic study of the lattice dynamics of the uranium rocksalt-structure
      compounds.

PMID- 9938045
TI  - Theoretical investigation of neutron scattering cross sections in Si and Ge.

PMID- 9938046
TI  - Optical properties of copper indium diselenide near the fundamental absorption
      edge.

PMID- 9938047
TI  - Atomic forces from electronic energies via the Hellmann-Feynman theorem, with
      application to semiconductor (110) surface relaxation.

PMID- 9938049
TI  - Low-temperature thermal properties of a sol-gel glass.

PMID- 9938048
TI  - Localized excitations in hydrogen-bonded molecular crystals.

PMID- 9938050
TI  - Brillouin scattering and three-body forces in argon at high pressures.

PMID- 9938051
TI  - Connection between tunneling and localized configurational relaxations in
      glasses.

PMID- 9938052
TI  - Volume and structural behavior of UP and USb up to 25 GPa.

PMID- 9938053
TI  - X-ray scattering from a two-dimensional liquid modulated by its periodic host.

PMID- 9938054
TI  - Orbital susceptibility of higher-stage graphite intercalation compounds.

PMID- 9938055
TI  - Electron-energy-loss and x-ray photoelectron spectra of MgF2.

PMID- 9938056
TI  - Off-center self-trapped excitons and creation of lattice defects in alkali halide
      crystals.

PMID- 9938057
TI  - Finite-element approach to band-structure analysis.

PMID- 9938059
TI  - Correlation effects on the oscillator strength of optical absorption: Sum rule
      for the one-dimensional Hubbard model.

PMID- 9938058
TI  - Temperature dependence of atomic transport in less-simple liquid metals.

PMID- 9938060
TI  - Density-functional calculation of the dynamic image plane at a metal surface:
      Reference-plane position of He- and H2-metal van der Waals interaction.

PMID- 9938061
TI  - Analogy between the effects of low-energy-ion and fast-neutron bombardments on
      the garnet structure.

PMID- 9938062
TI  - Thermionic emission in heterosystems with different effective electronic masses.

PMID- 9938063
TI  - Determination of valence-band discontinuity via optical transitions in ultrathin
      quantum wells.

PMID- 9938064
TI  - Quantum corrections to the Boltzmann equation for transport in semiconductors in
      high electric fields.

PMID- 9938066
TI  - Two-photon absorption spectra of direct and indirect materials: ZnO and AgCl.

PMID- 9938067
TI  - Origin of the 7.6-eV peak in the optical absorption spectrum of neutron- and
      heavy-ion-irradiated SiO2.

PMID- 9938065
TI  - Electronic structure of NiO.

PMID- 9938068
TI  - Enhancement of interaction constants in disordered systems: Experimental
      evidence.

PMID- 9938069
TI  - Impurity-enhanced disordering in the pseudobinary semiconductor alloy AlxGa1-xAs.

PMID- 9938070
TI  - Lattice-dynamical model for graphite and its alkali-metal intercalation
      compounds.

PMID- 9938072
TI  - Electrical-transport properties in the semimetallic compound LiGa.

PMID- 9938071
TI  - Polar optical-phonon scattering mobility in semiconductor quantum wells.

PMID- 9938074
TI  - Theories of homogeneous optical linewidths of impurities in glasses.

PMID- 9938073
TI  - Extension of the Lang-Kohn work-function calculation to the density of metallic
      hydrogen.

PMID- 9938075
TI  - Discontinuities in Kohn-Sham potentials in one and three dimensions.

PMID- 9938076
TI  - Theory of the bound magnetic polaron: A physical discussion and a comment.

PMID- 9938077
TI  - Reply to "Theory of the bound magnetic polaron: A physical discussion and a
      comment"

PMID- 9938078
TI  - Erratum: Theoretical investigation of the pressure dependences of energy gaps in
      semiconductors

PMID- 9938079
TI  - Fractal dimensionality of wave functions at the mobility edge: Quantum fractal in
      the Landau levels.

PMID- 9938080
TI  - Extended x-ray-absorption fine-structure study of quasicrystalline Al-Mn alloys.

PMID- 9938081
TI  - Quantum oscillations in one-dimensional metal rings: Average over disorder.

PMID- 9938082
TI  - Electronic structure and properties of epitaxial Fe on Cu(100): Theory and
      experiment.

PMID- 9938083
TI  - Intensity oscillations in the inverse photoemission cross section of an
      unoccupied surface state on Cu(001).

PMID- 9938084
TI  - Short-length-scale conductivity enhancement in a superlattice.

PMID- 9938085
TI  - Universal coefficients of perturbation expansion for the Anderson localization
      problem.

PMID- 9938086
TI  - Orientation of CH3O on Cu(110) as examined by near-edge x-ray-absorption fine
      structure spectroscopy.

PMID- 9938087
TI  - Pressure and temperature dependence of chromium photoluminescence in
      K2NaGaF6:Cr3+

PMID- 9938088
TI  - Phase locking in charge-density-wave transport.

PMID- 9938089
TI  - Binding and formation energies of native defect pairs in GaAs.

PMID- 9938090
TI  - Enhancement of defect-induced Raman modes at the fundamental absorption edge of
      electron-irradiated GaAs.

PMID- 9938091
TI  - Absorption spectra of Ti-doped GaAs.

PMID- 9938092
TI  - Properties of radiative recombinations in HgTe-CdTe heterostructures.

PMID- 9938093
TI  - Evaluation of the Stillinger-Weber classical interaction potential for tetragonal
      semiconductors in nonideal atomic configurations.

PMID- 9938094
TI  - Electron-hole liquid in InAs quantum wells under uniaxial stress.

PMID- 9938095
TI  - Observation by resonant tunneling of high-energy states in GaAs-Ga1-xAlxAs
      quantum wells.

PMID- 9938096
TI  - Rhombohedral phase stability of the group-VA elements.

PMID- 9938097
TI  - Bound-exciton transfer and photoluminescence undulation spectra for acceptors in
      ZnTe.

PMID- 9938098
TI  - Metastable changes of the electronic spin-lattice relaxation time in hydrogenated
      amorphous silicon.

PMID- 9938099
TI  - Origin of the Mn2+ optical transition in Mn-based II-VI diluted magnetic
      semiconductors.

PMID- 9938100
TI  - Tight-binding calculation of the band offset at the Ge-GaAs (110) interface using
      a local charge-neutrality condition.

PMID- 9938101
TI  - Electric field dependence of the resonant Raman scattering in GaAs-Ga1-xAlxAs
      quantum wells.

PMID- 9938103
TI  - Kinetics of aggregation of carbon clusters.

PMID- 9938102
TI  - Analytical determination of the density-of-gap-states distribution in amorphous
      semiconductors.

PMID- 9938104
TI  - Surface electronic structure of GaAs(110)1 x 1-Sb studied with angle-resolved
      photoelectron spectroscopy.

PMID- 9938106
TI  - Investigation of electronic relaxation in a classic paramagnet by selective
      excitation double-Mossbauer techniques: Theory and experiment.

PMID- 9938105
TI  - Stretched exponential spin recoveries in an ytterbium-doped lead phosphate glass.

PMID- 9938108
TI  - Mossbauer study of stage-2 FeCl3-graphite.

PMID- 9938107
TI  - Crystal-field states of the Ce3+ ion in CeF3: A demonstration of vibronic
      interaction in ionic rare-earth compounds.

PMID- 9938109
TI  - Theoretical investigation of the 67Zn Mossbauer isomer shifts in the zinc
      chalcogenides.

PMID- 9938110
TI  - Magnetic resonance in gold-iron alloys near the percolation limit.

PMID- 9938111
TI  - Dynamical properties of LiI

PMID- 9938112
TI  - Energy levels of channeled ions.

PMID- 9938113
TI  - Coupled (Zeeman-tunnel)-lattice relaxation of the methyl group in copper acetate.

PMID- 9938114
TI  - Coherence and pair-breaking effect in the heavy-fermion superconductor CeCu2Si2.

PMID- 9938116
TI  - Inelastic electron lifetime in niobium films.

PMID- 9938115
TI  - Determination of spin-fluctuation parameters from the specific heat of almost
      ferromagnetic Fermi liquids.

PMID- 9938117
TI  - 3He specific heat and thermometry at millikelvin temperatures.

PMID- 9938118
TI  - ac magnetic susceptibility, Meissner effect, and bulk superconductivity.

PMID- 9938119
TI  - Phonon decay in two-dimensional liquid 4He.

PMID- 9938121
TI  - Helium at nonzero temperatures: A variational density-matrix approach for Bose
      fluids.

PMID- 9938120
TI  - Band structure and superconductivity in Lu at high pressures.

PMID- 9938123
TI  - Kinetics of the order-disorder transition of the two-dimensional anisotropic next
      nearest-neighbor Ising model with Kawasaki dynamics.

PMID- 9938122
TI  - Anisotropic superconductors containing transition-metal impurities: Local spin
      fluctuations.

PMID- 9938124
TI  - Electronic states in continuous random networks: Rivier lines as half-integer
      magnetic flux lines.

PMID- 9938125
TI  - Paramagnon versus lowest-order Hartree-Fock contributions in disordered nearly
      magnetic two- and three-dimensional itinerant fermion systems and the
      renormalization of the Stoner enhancement by disorder.

PMID- 9938126
TI  - Nuclear relaxation and antiferromagnetic critical effects in organic conductors.

PMID- 9938127
TI  - Solid-state reaction and structure in compositionally modulated zirconium-nickel
      and titanium-nickel films.

PMID- 9938128
TI  - Brillouin spectroscopy of polarization fluctuations in a a Rb1-x(NH4)xH2PO4
      glass.

PMID- 9938129
TI  - Magnetic behavior of the semimagnetic semiconductor (Cd1-xMnx)3As2.

PMID- 9938130
TI  - Quantum corrections to the thermodynamics of nonlinear systems.

PMID- 9938131
TI  - Comparative Monte Carlo and mean-field studies of random-field Ising systems.

PMID- 9938133
TI  - Cesium adsorption on graphite (0001) surface: The phase diagram.

PMID- 9938132
TI  - Ising domain growth barriers on a Cayley tree at percolation.

PMID- 9938134
TI  - Critical temperatures and the compensation temperatures of disordered and
      amorphous ferrimagnetic Ising systems.

PMID- 9938135
TI  - Monte Carlo renormalization-group study of tricritical behavior in two
      dimensions.

PMID- 9938136
TI  - Self-consistent mode-coupling theory of quantum percolation.

PMID- 9938137
TI  - Dislocation motion in quasicrystals and implications for macroscopic properties.

PMID- 9938138
TI  - Observation of antiferromagnetic resonance in epitaxial films of MnF2.

PMID- 9938139
TI  - Two-band model for the magnetism of iron.

PMID- 9938140
TI  - Spinodals and transfer matrices in d=1 models.

PMID- 9938141
TI  - Renormalization-group approach to quantum percolation and Anderson localization.

PMID- 9938142
TI  - Second virial coefficients in soliton free energies.

PMID- 9938143
TI  - Anomalous transport in lattice and continuum percolating systems.

PMID- 9938145
TI  - Critical dynamics of the kinetic Ising model on fractal geometries. II. Sierpin
      acuteski carpets.

PMID- 9938144
TI  - High-pressure phase diagram of silver mercury iodide (Ag2HgI4).

PMID- 9938146
TI  - Neutron scattering study of the nucleation and growth process at the pressure
      induced first-order phase transformation of RbI.

PMID- 9938147
TI  - Band-filling and magnetic-field effects on the phase diagram of one-dimensional
      conductors.